PuriActives® AcneZero — Multi-Pathway Botanical Blemish Care System

PURIACTIVES® MULTI-BOTANICAL BLEMISH CARE SYSTEM

AcneZero 痘必清

A Multi-Pathway, Botanical Synergy System for Blemish-Prone Skin

From Single-Target to Multi-Pathway Care

SebumInflammationOxidative StressMicrobiomeSoothing & Barrier

PuriPharm Co., Ltd.B2B technical & marketing material · For cosmetics industry professionals only

CONTENTS

A complete evidence chain from mechanism to commercial value

01	Understanding Blemish-Prone Skin — The Mechanism Map of a Multifactorial Skin Condition
02	Product Overview — Composition, Positioning & the Phospholipid-Based Active System
03	The Five Axes — Ingredient-Level Scientific Evidence & Mechanisms
04	Botanical Actives in Focus — Scientific Profiles of Seven Plant Extracts
05	Synergy · Claims · Applications — From Evidence Grading to B2B Value

Evidence grading: A = AcneZero’s own product data; B = published ingredient literature; C = reasonable extrapolation from ingredient information. Ingredient-level literature results are not equivalent to finished-product efficacy.

01

Understanding Blemish-Prone Skin

Acne is not a simple “bacterial problem.” It is a multifactorial condition in which sebum production, follicular keratinization, microbes, inflammatory cascades and oxidative stress intertwine — and this is exactly where single-target solutions reach their limits.

In this chapter ｜ The acne pathogenesis network · The oxidative-stress amplifier · The limits of single-target care

Acne Pathogenesis: A Network of Five Mutually Amplifying Pathways

01 UNDERSTANDING BLEMISH-PRONE SKIN ｜ ACNE PATHOGENESIS

① Excess sebum production	IGF-1 / androgen signaling drives sebaceous lipid synthesis via PI3K–Akt–mTORC1, providing the substrate for downstream oxidation and microbial imbalance.
② Abnormal follicular keratinization	Lipid peroxides (e.g., squalene monohydroperoxide) promote keratinocyte hyperproliferation; the follicle becomes plugged and microcomedones form.
③ Microbes & dysbiosis	Cutibacterium acnes (formerly Propionibacterium acnes) overgrows in anaerobic, lipid-rich follicles and activates innate immunity via TLR2; biofilms and resistant strains make management harder.
④ Inflammatory cascade amplification	The TLR2／TLR4 → NF-κB／MAPK pathway drives the release of IL-1β, IL-6, IL-8 and TNF-α, determining redness, swelling, pain and the risk of post-inflammatory hyperpigmentation.
⑤ Oxidative stress & lipid peroxidation	UV, pollution and microbes jointly trigger sebum oxidation; oxidized lipids in turn aggravate abnormal keratinization and inflammation — the network’s “amplifier.”

Mechanistic framework: Cong TX, et al. Arch Dermatol Res. 2019;311(5):337-349. DOI:10.1007/s00403-019-01908-x; Dréno B, et al. J Eur Acad Dermatol Venereol. 2018;32(Suppl 2):5-14; Condrò G, et al. Pharmaceuticals. 2023;16(12):1704.

The Underestimated Amplifier: Squalene Peroxidation

01 UNDERSTANDING BLEMISH-PRONE SKIN ｜ SQUALENE PEROXIDATION

Squalene accounts for about 10–15% of sebum lipids, and its multiple double bonds make it highly prone to oxidation into squalene monohydroperoxide — a strongly comedogenic compound. In vivo studies confirm that both squalene and its peroxidized forms are significantly higher in acne-prone skin than in healthy skin, correlating positively with sebum output and porphyrin intensity; acne-prone skin also shows higher transepidermal water loss (TEWL), indicating an impaired barrier.

Reading the chart: squalene peroxidation is higher in inflammatory lesion areas than in non-inflammatory areas — lipid peroxidation moves in the same direction as inflammation, forming a vicious cycle of “oxidation → inflammation → more oxidation.”

Implications for formulation strategy

· “Antibacterial only” cannot break the oxidation cycle — antioxidant and anti-lipid-peroxidation design must be part of anti-blemish formulations;· The barrier of blemish-prone skin is already compromised, so efficacy systems must be both low-irritation and barrier-friendly;· Oxidation management is also linked to post-inflammatory hyperpigmentation (PIH) risk — the shared foundation of “fighting acne” and “post-blemish recovery.”

Data redrawn from: Condrò G, Sciortino R, Perugini P. Squalene peroxidation and biophysical parameters in acne-prone skin: a pilot “in vivo” study. Pharmaceuticals (Basel). 2023;16(12):1704. DOI:10.3390/ph16121704 (mechanistic background literature, not data on this product)

The Ceiling of Single-Target Solutions Is Exactly the Opportunity for Multi-Pathway Care

01 UNDERSTANDING BLEMISH-PRONE SKIN ｜ UNMET NEEDS

Challenges of traditional single-pathway approaches

The answer from multi-pathway botanical synergy

Antibiotic pathway — C. acnes resistance keeps rising; long-term use faces resistance and microbiome disturbance;Retinoid pathway — effective for keratinization, but irritation, dryness and peeling limit use on sensitive, blemish-prone skin;Single-botanical pathway — usually covers only “antibacterial” or “anti-inflammatory,” hardly matching acne’s multifactorial mechanism;The overlooked link — oxidative stress and barrier damage have long been absent from the anti-acne narrative, yet directly affect recurrence and post-blemish condition.

● Division of labor across ingredients: different botanicals act on sebum, inflammation, oxidation, microbes and the barrier — covering the mechanistic network rather than a single point;● Non-antibiotic antimicrobial strategy: plant-derived actives (e.g., berberine-type alkaloids) show C. acnes inhibition and anti-biofilm potential in the literature, avoiding the antibiotic-resistance narrative;● Cosmetics-compliant storytelling: framed as “blemish-prone skin care / oil control / soothing,” within cosmetic claim boundaries;● Gentle enough for daily use: product safety data support no skin irritation and no eye irritation, suiting long-term care scenarios.

Note: the left column is background at the level of literature and industry consensus, used to explain formulation design logic; it is not an evaluation of any pharmaceutical regimen. The “non-antibiotic antimicrobial strategy” on the right is ingredient-level literature evidence (Grade B).

Background: Cong TX, et al. Arch Dermatol Res. 2019;311(5):337-349; Sun L, et al. Front Microbiol. 2023;14:1276383. DOI:10.3389/fmicb.2023.1276383; product safety: AcneZero MSDS v1.1 (Grade A)

02

Product Overview ｜ AcneZero

Seven botanical actives × a phospholipid-based active system: with the ingredient list and MSDS as the highest factual basis, defining a modern anti-blemish ingredient by mechanistic division of labor rather than “single-point sterilization.”

In this chapter ｜ Positioning · Eleven-component formula · Phospholipid-based active system · The five-axis master model

Positioning: A Multi-Pathway Ingredient for Blemish-Prone Skin Management

02 PRODUCT OVERVIEW ｜ PRODUCT IDENTITY

PuriActives® AcneZero is a multi-botanical anti-blemish ingredient developed by PuriPharm for cosmetics customers worldwide. Its active core combines seven botanical extracts — Canarium album (olive) leaf extract, bioflavonoids, Salvia miltiorrhiza extract, Gardenia jasminoides fruit extract, Mahonia fortunei extract, silymarin, and Stevia rebaudiana leaf/stem extract — carried by a phospholipid-based active system, covering five axes: sebum – inflammation – oxidation – microbiome – barrier. It is not a “single sterilizing molecule,” but an evidence-graded, multi-pathway solution.

Product information (per MSDS v1.1)
Trade name	AcneZero 痘必清 (PuriActives® brand)
Intended use	Cosmetic skincare ingredient (B2B industrial use)
Appearance & odor	Yellow liquid, characteristic odor
Solubility	Water-soluble (20°C)
Storage	4–25°C, protect from light
Safety	No skin irritation, no eye irritation (MSDS data, Grade A)
Regulatory status	Listed in China’s Inventory of Existing Chemical Substances (IECIC)
Document version	MSDS v1.1 (2019-07-13)

POSITIONING IN ONE SENTENCE

“From single-target anti-acne to multi-pathway blemish-prone skin management.”

· Target customers: cosmetics brands, formulators, OEM/ODM R&D teams· Suitable dosage forms: serums, toners, lotions, masks and other water-based systems· Claim framework: oil control · soothing · microbiome balance · antioxidant · barrier support · post-blemish tone care

Product information: PuriPharm AcneZero MSDS v1.1 and AcneZero Ingredient List (internal documents, Grade-A factual basis). Please confirm recommended dosage and compatibility parameters with the PuriPharm technical team.

Eleven Components: A Formula You Can Read Mechanistically

02 PRODUCT OVERVIEW ｜ COMPOSITION

Component (INCI)	CAS No.	Typical value (%)
Canarium Album Leaf Extract	—	2.5
Bioflavonoids	61788-55-4	3.0
Salvia Miltiorrhiza Extract	90106-50-6	2.5
Gardenia Jasminoides Fruit Extract	92457-01-7	3.5
Mahonia Fortunei (Chinese mahonia) Extract	—	3.0
Silymarin	22888-70-6	0.5
Stevia Rebaudiana Leaf/Stem Extract	91722-21-3	5.0
Phospholipids	123456-35-0	5.0
Glycerin	56-81-5	38.0
Propylene Glycol	57-55-6	31.5
Aqua (Water)	7732-18-5	5.5

Formula structure (grouped by typical values)

· Botanical actives total 20% and phospholipids 5%, forming the functional “active + delivery” layer;· Glycerin, propylene glycol and water form the humectant solvent base, also responsible for mildness and system stability.

Data source: PuriPharm AcneZero Ingredient List and AcneZero MSDS v1.1 (Grade A — the highest factual basis, never modified for marketing). Values shown are typical values from the company’s ingredient list; specification ranges are detailed in the product ingredient list.

The Phospholipid-Based Active System: A Classic Skin-Affinity Delivery Strategy

02 PRODUCT OVERVIEW ｜ PHOSPHOLIPID-BASED ACTIVE SYSTEM

AcneZero builds its active-carrier system on 5% phospholipids. Phospholipids share a natural affinity with stratum corneum lipids and are a classic skin-friendly delivery and stabilization strategy in cosmetic science, helping water- and oil-soluble botanical actives coexist stably in one system.

● Skin-lipid affinity: the phospholipid bilayer is homologous to stratum corneum lipids, favoring spreading and retention of actives on the skin surface;● Classic delivery evidence: as early as 1980, Mezei and Gulasekharam showed that a phospholipid system (liposomal lotion) increased skin delivery of triamcinolone acetonide to 4–5× that of an ointment base — laying the literature foundation for phospholipids in dermal delivery;● Multi-phase stability: the emulsifying and dispersing capacity of phospholipids supports the uniform coexistence of seven botanicals with the water-based vehicle;● Barrier-friendly: phospholipids themselves are mild, skin-lipid-related ingredients, matching the fragile-barrier needs of blemish-prone skin.

Hydrophilic heads · facing the water phaseHydrophobic tails · carrying lipophilic activesHydrophilic heads · facing the water phase

Schematic: phospholipid bilayer structure (self-drawn illustration)

Claim boundary: AcneZero is a Phospholipid-based Active System. This material makes no liposome, nanovesicle or nano-delivery claims for it; liposome-related literature is cited only as classic supporting evidence for the dermal-delivery value of phospholipid systems.

Reference: Mezei M, Gulasekharam V. Liposomes — a selective drug delivery system for the topical route of administration. Life Sci. 1980;26:1473-1477 (Grade-B background evidence). Phospholipid content: AcneZero Ingredient List (Grade A).

The AcneZero Five-Axis Model

02 PRODUCT OVERVIEW ｜ MULTI-PATHWAY MODEL

AcneZero ｜ Seven botanicals × phospholipid-based system

A1 Sebum management	Mahonia (berberine) · olive leaf · bioflavonoidsTargeting SREBP-1／PPAR-γ lipid-synthesis signaling
A2 Inflammation management	Salvia · gardenia fruit · bioflavonoids · olive leaf · steviaTargeting the TLR2/4 → NF-κB／MAPK inflammatory cascade
A3 Oxidative-stress management	Silymarin · bioflavonoids · olive leaf · steviaScavenging free radicals and inhibiting sebum lipid peroxidation
A4 Microbiome management	Mahonia (berberine) · salvia · silymarinNon-antibiotic C. acnes management and biofilm inhibition
A5 Soothing & barrier support	Stevia · phospholipids · gardenia fruitTight-junction protein and skin-friendly lipid support

The model summarizes mechanistic division of labor based on published ingredient literature (combined Grade B/C evidence); it is not a clinical-trial conclusion for this product. Axis-by-axis evidence is detailed in Chapter 3. Composition: AcneZero Ingredient List (Grade A).

03

The Five Axes · Ingredient-Level Scientific Evidence

Each axis answers a formulation question: which ingredient, acting on which step, with evidence from where, and how strong. All data are annotated with study models and literature sources.

In this chapter ｜ A1 Sebum · A2 Inflammation · A3 Oxidative stress · A4 Microbiome · A5 Soothing & barrier

Axis 1 · Sebum Management: Regulating Lipid-Synthesis Signaling

03 THE FIVE AXES ｜ AXIS 1 · SEBUM CONTROL

Key signaling axis of sebum synthesis (mechanistic background)

IGF-1 / androgens → PI3K–Akt → SREBP-1／PPAR-γ → Excess sebum

Ingredient-level evidence (sebocyte models)

Berberine (marker compound of Mahonia)｜ Grade BIn SZ95 human sebocytes, 40 μM berberine significantly downregulated the key lipogenic enzymes FASN and DGAT1, reduced fatty-acid and triglyceride secretion, and inhibited NF-κB p65 activation (J Inflamm Res, 2025).

Olive leaf extract｜ Grade C (literature species Olea europaea, extrapolation reference)In SEB-1 sebocytes it significantly inhibited linoleic-acid-induced lipid accumulation without cytotoxicity, and downregulated AKT／ERK phosphorylation and PPAR-γ／SREBP-1 expression (Curr Issues Mol Biol, 2026).

Mechanistic benchmark: EGCG (polyphenol)｜ literature benchmarkReduced sebum synthesis in SEB-1 cells via AMPK–SREBP-1 and improved acne in an 8-week randomized split-face human trial (J Invest Dermatol, 2013) — validating the clinical feasibility of the “botanical polyphenols regulate sebum” pathway.

Division of labor in AcneZero: Mahonia extract (berberine source; botanical basis in Chapter 4) ｜ olive leaf extract (polyphenols; sebum-regulation extrapolation reference) ｜ bioflavonoids (polyphenol-family synergy)

Sources: Berberine inhibits acne-related lipid secretion and inflammation by regulating the hsa-miR-3150a-3p/TP53 pathway. J Inflamm Res. 2025; Kim J, et al. Curr Issues Mol Biol. 2026;48(6):549. DOI:10.3390/cimb48060549; Yoon JY, et al. J Invest Dermatol. 2013;133(2):429-440; Cong TX, et al. 2019 (signaling-axis background)

Axis 2 · Inflammation Management: Intercepting the TLR → NF-κB Cascade

03 THE FIVE AXES ｜ AXIS 2 · INFLAMMATION

The C. acnes-triggered inflammatory cascade (mechanistic background)

C. acnes & its products → TLR2／TLR4 → NF-κB／MAPK → IL-1β · IL-6 · IL-8 · TNF-α → Redness · lesions · PIH

Interception point 1: the receptor layer (TLR2／TLR4 downregulation)Quercetin (representative bioflavonoid)｜ Grade B　In C. acnes-stimulated HaCaT keratinocytes, THP-1 and RAW264.7 cells, it inhibited inflammatory cytokine release and downregulated TLR2, p38／ERK／JNK phosphorylation and MMP-9, with in vivo anti-inflammatory validation in a mouse-ear model (Int Immunopharmacol, 2021).

Interception point 2: the signaling layer (TAK1／NF-κB inhibition)Tanshinone IIA (marker compound of Salvia)｜ Grade B　Concentration-dependently inhibited LPS-induced MCP-1, IL-6, TNF-α and NO production, downregulated TLR4 expression, and suppressed TAK1 phosphorylation and NF-κB p65 nuclear translocation (Int J Mol Med, 2019).

Why “multiple interception points” beat single-point inhibition:· Acne inflammation is driven in parallel by multiple receptor–signaling routes; blocking a single node is easily bypassed;· In the literature, AcneZero’s botanicals act at different levels — TLR2 (quercetin), TLR4／TAK1 (tanshinone IIA, geniposide), NF-κB (stevioside, berberine);· This multi-point division of labor is the design logic of the product’s inflammation-management axis (see the evidence matrix below).

Sources: Lim HJ, et al. Int Immunopharmacol. 2021;96:107557. DOI:10.1016/j.intimp.2021.107557; Meng Z, et al. Int J Mol Med. 2019;43(4):1847-1858. DOI:10.3892/ijmm.2019.4100; cascade background: Cong TX, et al. 2019; Dréno B, et al. 2018

Inflammation-Management Evidence Matrix: Five Ingredients, Four Interception Layers

03 THE FIVE AXES ｜ AXIS 2 · EVIDENCE MATRIX

Ingredient / marker	Study model	Key results	Reference (Grade B)
Quercetin (representative bioflavonoid)	C. acnes-stimulated HaCaT／THP-1／RAW264.7; mouse-ear model	↓IL-6／IL-8／TNF-α; ↓TLR2, p38／ERK／JNK, MMP-9	Lim et al. Int Immunopharmacol. 2021
Tanshinone IIA (Salvia marker)	LPS-stimulated vascular smooth muscle cells	↓MCP-1／IL-6／TNF-α／NO; ↓TLR4–TAK1–NF-κB	Meng et al. Int J Mol Med. 2019
Gardenia fruit extract / geniposide	LPS-induced inflammation models; in vivo zebrafish model	↓IL-1β／IL-6／TNF-α; ↓TLR4 signaling, NF-κB p65／MAPK	Chen et al. Exp Ther Med. 2021; Song et al. Inflammation. 2014
Stevioside (stevia marker)	Cellular oxidative-inflammation model	↓IL-6／IL-8／TNF-α; ↓NF-κB／IκB／ERK1/2 phosphorylation	Xu et al. Antioxidants. 2023
Berberine (Mahonia marker)	C. acnes mouse-ear acne model	↓Ear-tissue IL-6／IL-1β／TNF-α; reduced ear thickness and colonizing bacterial load	Sun et al. Front Microbiol. 2023

How to read: the above are published ingredient-level studies (Grade B) covering cell, zebrafish and mouse in vivo models; they support the mechanistic division of labor of ingredients in the formula and are not equivalent to finished-product human efficacy conclusions for AcneZero. A baicalin rabbit-ear acne study (Yang et al. 2019) provides parallel evidence for flavonoid anti-inflammation.

Full citations are listed in the References at the end ([6][12][13][15][4][17]).

Axis 3 · Oxidative-Stress Management: Protecting Sebum from Oxidation

03 THE FIVE AXES ｜ AXIS 3 · OXIDATIVE DEFENSE

Squalene peroxidation is the amplifier connecting “oiliness” and “inflammation.” AcneZero’s antioxidant axis is built on four polyphenol systems — silymarin, bioflavonoids, olive leaf and stevia — with literature evidence covering free-radical scavenging, antioxidant-enzyme upregulation and lipid-peroxidation inhibition.

Silymarin｜ Grade BA classic flavonolignan antioxidant. A human study of a silymarin-containing antioxidant serum showed reduced skin lipid peroxidation, plus improvement in acne-related erythema and post-inflammatory hyperpigmentation (J Drugs Dermatol, 2024). → Human clinical data in Chapter 4 (Silymarin)

Stevioside｜ Grade BAt 250 μM in cell models, stevioside significantly reduced ROS and MDA (a lipid-peroxidation marker) while upregulating T-SOD, CAT and GSH-Px antioxidant enzymes, and inhibited NF-κB／ERK1/2 phosphorylation (Antioxidants, 2023).

Olive-leaf polyphenols + bioflavonoids｜ Grade B/COleuropein reduced ROS in a UVB model (Grade-C extrapolation; literature species Olea europaea); the ortho-dihydroxyl structure of bioflavonoids confers strong radical-scavenging capacity, with efficiency linked to the C2–C3 double bond and 4-carbonyl features (structure–activity review, 1999).

Breaking the vicious cycle: the antioxidant axis directly reduces the formation of squalene-peroxidation substrates — lowering the upstream drive of abnormal keratinization while cutting the continuous fuel that oxidized lipids supply to the inflammatory cascade. This is the structural difference between AcneZero and “oil-control-only, sterilization-only” solutions.

Sources: J Drugs Dermatol. 2024;23(4). DOI:10.36849/JDD.8120; Xu Q, et al. Antioxidants (Basel). 2023;12(5):1070. DOI:10.3390/antiox12051070; Zhang DQ, et al. Food and Fermentation Industries. 1999;25(6):52-57; Kim J, et al. 2026

Axis 4 · Microbiome Management: A Non-Antibiotic Antimicrobial Pathway

03 THE FIVE AXES ｜ AXIS 4 · MICROBIOME BALANCE

Data redrawn from the original table of Sun et al. 2023 (4 strains including ATCC reference and clinical isolates); inhibition-zone diameters 32.07–35.27 mm. The reference antibiotic doxycycline in the same study had an MIC of 0.31 μg/mL — berberine is a plant-derived, non-antibiotic molecule whose value lies in avoiding the antibiotic-resistance narrative.

Beyond inhibition: biofilms and in vivo validation● Anti-biofilm: 10–60 μM berberine concentration-dependently inhibited C. acnes growth and biofilm formation, and downregulated cell-wall synthesis genes murC／murD／mraY／murG (Front Microbiol, 2023; J Inflamm Res, 2025);● In vivo model: in a C. acnes mouse-ear model, berberine reduced ear thickness, ear weight and colonizing bacterial load, with ear-tissue IL-6／IL-1β／TNF-α declining in parallel;● Tanshinone synergy: a review reports tanshinones’ inhibitory and anti-biofilm activity against C. acnes (including resistant strains) (Fitoterapia, 2025);● Silymarin support: improvements in lesions and microbiome-related indices were observed in human studies (see Chapter 4).

From “sterilization” to “microbiome balance”: modern dermatology no longer pursues total sterilization, but manages C. acnes overgrowth and biofilms. A plant-derived, multi-target antimicrobial strategy is consistent with this philosophy — and does not constitute an antibiotic-type claim.

Sources: Sun L, et al. Front Microbiol. 2023;14:1276383. DOI:10.3389/fmicb.2023.1276383 (in vitro + mouse-ear model, Grade B); J Inflamm Res. 2025 (SZ95 cells, Grade B); Zhang T, et al. Fitoterapia. 2025 (review). Ingredient literature data, not measured on this product.

Axis 5 · Soothing & Barrier: The Safety Foundation of Blemish Care

03 THE FIVE AXES ｜ AXIS 5 · SOOTHING & BARRIER

The problem: the barrier of blemish-prone skin is inherently fragile. In vivo research shows that TEWL (transepidermal water loss) is significantly higher in acne-prone skin than in healthy skin — the stratum corneum barrier is impaired (Pharmaceuticals, 2023). This means an anti-blemish ingredient that adds irritation would instead worsen redness and discomfort: mildness is not a bonus, but the entry ticket.

AcneZero’s triple barrier-friendly design● Stevia (stevioside)｜ Grade B: upregulates tight-junction proteins claudin-1, occludin and ZO-1, supporting barrier integrity (Antioxidants, 2023);● Phospholipid system｜ Grade A/B: a skin-lipid-homologous, skin-friendly structure combining active carrying with barrier care;● Glycerin–propylene glycol humectant base｜ Grade A: a classic humectant pair that relieves the dryness and flaking common in blemish-prone skin.

0Skin irritation(MSDS conclusion: no skin irritation)

0Eye irritation(MSDS conclusion: no eye irritation)

Product-owned safety data ｜ Grade A · Source: PuriPharm AcneZero MSDS v1.1 — one of the few Grade-A (product-owned) data points in this material.

What this means for formulators:· Suitable for formulas positioned for sensitive, blemish-prone skin and long-term daily care;· The soothing narrative is backed by ingredient-level barrier literature, not just a “mildness claim”;· Together with the sebum, inflammation, oxidation and microbiome axes, it completes a full care loop.

Sources: Condrò G, et al. Pharmaceuticals (Basel). 2023;16(12):1704 (TEWL background); Xu Q, et al. Antioxidants (Basel). 2023;12(5):1070 (tight-junction proteins, Grade B); AcneZero MSDS v1.1 (safety, Grade A).

04

Botanical Actives in Focus

Seven botanicals, seven scientific profiles: botanical origin, marker actives, key literature evidence, and each one’s role in the five-axis system.

In this chapter ｜ Bioflavonoids · Salvia · Silymarin · Olive leaf · Mahonia · Gardenia fruit · Stevia

Bioflavonoids: Dual Inflammation–Oxidation Management from the Polyphenol Family

04 BOTANICAL ACTIVES ｜ BIOFLAVONOIDS

Citrus fruits are a classic source of bioflavonoids (illustrative image)

INCI	Bioflavonoids
CAS	61788-55-4
Role in system	Dual support: inflammation · oxidation

Structure determines activity: flavonoids’ radical-scavenging capacity is directly tied to molecular structure — the C2–C3 double bond, the 4-carbonyl group and ortho-dihydroxyl groups are the key features of efficient scavengers; the ranking follows a clear structure–activity relationship (e.g., rutin > quercetin > morin > hesperidin, system-dependent).

Quercetin: direct evidence in acne-inflammation models｜ Grade BIn C. acnes-stimulated keratinocytes and immune cells it inhibited cytokines and downregulated TLR2／MAPK／MMP-9, with in vivo validation in a mouse-ear model (Int Immunopharmacol, 2021).

Baicalin: parallel evidence in a rabbit-ear acne model｜ Grade BRNA-seq showed baicalin reduced rabbit-ear acne lesions, lowered serum TNF-α／IL-1β／IL-6／IL-8, and broadly suppressed TNF signaling (J Tradit Chin Med Sci, 2019).

Why flavonoids are the “infrastructure” of anti-blemish blends: one molecular family covers both radical scavenging (Axis 3) and inflammatory-signal inhibition (Axis 2), with structural diversity, wide sourcing and a long safety record — making bioflavonoids a natural hub connecting the axes. The human anti-acne study of EGCG (J Invest Dermatol, 2013) further proves the clinical feasibility of the polyphenol pathway.

Sources: Zhang DQ, Tai JX, Fu Q. Research and application of bioflavonoids. Food and Fermentation Industries. 1999;25(6):52-57; Lim HJ, et al. 2021; Yang X, et al. J Tradit Chin Med Sci. 2019;6(3):201-210; Yoon JY, et al. 2013 (all Grade-B ingredient literature)

Salvia Miltiorrhiza Extract: A Dual Blockade of Microbes and Inflammation

04 BOTANICAL ACTIVES ｜ SALVIA MILTIORRHIZA

Dried Salvia miltiorrhiza root (illustrative image)

INCI	Salvia Miltiorrhiza Extract
CAS	90106-50-6
Role in system	Dual axes: microbiome · inflammation

Marker actives: tanshinones (lipophilic diterpene quinones) and salvianolic acids (water-soluble phenolic acids).

Microbiome axis｜ Grade B　A 2025 Fitoterapia review systematically summarized tanshinones’ molecular mechanisms against acne, including inhibitory activity against C. acnes (including resistant strains) and anti-biofilm effects — together with berberine forming the product’s plant-derived antimicrobial combination.

Inflammation axis｜ Grade B　Tanshinone IIA concentration-dependently inhibited MCP-1, IL-6, TNF-α and NO via the TLR4／TAK1／NF-κB pathway (Int J Mol Med, 2019).

Tanshinone IIA’s interception levels in inflammatory signaling

↓ TLR4 → ↓ p-TAK1 → ↓ NF-κB nuclear translocation → ↓ Inflammatory factors

Reading the diagram: tanshinone IIA suppresses three levels simultaneously — receptor (TLR4), kinase (TAK1) and transcription factor (NF-κB). This is the “multi-interception-point” design embodied within a single ingredient (Meng et al. 2019, LPS cell model).

Sources: Zhang T, et al. Tanshinone in acne therapeutics. Fitoterapia. 2025 (review); Meng Z, et al. Int J Mol Med. 2019;43(4):1847-1858. DOI:10.3892/ijmm.2019.4100 (Grade-B ingredient literature)

Silymarin: The Antioxidant Mainstay with Human Clinical Data

04 BOTANICAL ACTIVES ｜ SILYMARIN

Data redrawn from J Drugs Dermatol. 2024: lesion and oiliness endpoints from the monotherapy study (n=56, 12 weeks); erythema / dryness / scaling from the combination-regimen tolerability study (n=40). The studies also reported reduced lipid peroxidation and improved post-inflammatory hyperpigmentation.

Milk thistle (Silybum marianum)

A second human study (0.5% silymarin serum): 22 subjects with mild-to-moderate acne, 4 weeks: mGAGS score, lesion counts and melanin index decreased significantly, with no adverse events (J Cosmet Dermatol, 2023).

Role in AcneZero:● The human-evidence anchor of the oxidative-stress axis: anti-lipid-peroxidation maps directly onto the squalene-peroxidation mechanism;● The melanin-index reduction connects to the post-blemish tone-care narrative (see Chapter 5);● Its typical value in the ingredient list is 0.5% — the same order of magnitude as the concentrations used in clinical studies (Grade-A formula fact).

Sources: A silymarin antioxidant serum improves facial acne alone and as part of a treatment regimen. J Drugs Dermatol. 2024;23(4). DOI:10.36849/JDD.8120; Kim J, et al. J Cosmet Dermatol. 2023;22(2):561-568. DOI:10.1111/jocd.15439 (Grade-B ingredient literature, not clinical data on this product)

Olive Leaf Extract: A Polyphenol Carrier for Sebum–Inflammation Dual Regulation

04 BOTANICAL ACTIVES ｜ OLIVE LEAF

Olive branches and leaves (illustrative image)

INCI	Canarium Album Leaf Extract
CAS	—
Role in system	Sebum · inflammation · oxidation

Sebocyte evidence｜ Grade C (literature species Olea europaea, extrapolation reference)A 2026 study (SEB-1 human sebocytes): olive leaf extract significantly inhibited linoleic-acid-induced lipid accumulation without cytotoxicity; downregulated AKT／ERK phosphorylation and PPAR-γ／SREBP-1 expression; and reduced IL-8, TNF-α and PGE2 in C. acnes- or UVB-stimulated HaCaT keratinocytes (Curr Issues Mol Biol, 2026).

Antioxidant evidence for the marker compound oleuropein｜ Grade CProteomics showed oleuropein downregulated pro-inflammatory cytokines and upregulated antioxidant defenses in H₂O₂-stimulated HaCaT cells (2025); oleuropein and hydroxytyrosol are skin-permeable elastase／collagenase inhibitors with synergistic antioxidant activity in human dermal fibroblasts (Int J Food Sci Nutr, 2022).

Evidence boundary (scientific integrity):· The in vitro studies above used Olea europaea leaf; this product uses Canarium album leaf extract, and the data serve as a reference from related olive-leaf polyphenol research (Grade-C reasonable extrapolation), not as direct measurements on this ingredient in the product;· In the same study, no direct antibacterial activity was detected for this extraction process — the product therefore positions olive leaf for sebum regulation, anti-inflammation and antioxidant support, while the microbiome axis is carried by Mahonia, Salvia and silymarin;· This is exactly the point of the five-axis division of labor: let each ingredient do what its evidence does best.

Sources: Kim J, et al. Curr Issues Mol Biol. 2026;48(6):549. DOI:10.3390/cimb48060549; Li H, et al. Int J Food Sci Nutr. 2022;73(4):460-470; INCI information: AcneZero Ingredient List (Grade A)

Mahonia Fortunei: The Botanical Source of Berberine

04 BOTANICAL ACTIVES ｜ MAHONIA

Mahonia plant (image source: Wikimedia Commons)

INCI	Mahonia Fortunei (Chinese mahonia) Extract
CAS	—
Role in system	Core of the microbiome axis

Botanical basis (patent literature): Chinese patent CN1069493A records that Mahonia (Berberidaceae) rhizomes contain 1.5–2.4% berberine, and the refining process described therein achieves 98.1% berberine purity — a clear documentary basis for Mahonia as a botanical source of berberine.

Berberine’s anti-acne evidence: in vitro MIC 6.25–12.5 μg/mL, anti-biofilm activity, downregulation of cell-wall synthesis genes, and anti-inflammatory effects in a mouse-ear model (see Chapter 3, Axis 4); inhibition of lipid synthesis and NF-κB in SZ95 sebocytes (see Chapter 3, Axis 1).

Same-genus support｜ Grade B: bisbenzylisoquinoline alkaloids from Mahonia aquifolium show lipoxygenase (LOX) inhibition and anti-lipid-peroxidation activity, highly correlated with each other (r=0.9533) — suggesting the genus’s alkaloids combine microbiome-management and antioxidant potential (Pharmazie, 1996).

Sources: Liao ZJ. Process for extracting and refining berberine from Mahonia. Chinese patent CN1069493A, published 1993-03-03; Bezáková L, et al. Pharmazie. 1996;51(10):758-761; Sun L, et al. 2023; J Inflamm Res. 2025 (Grade-B ingredient literature)

Gardenia Fruit Extract: The Bridge from Anti-Inflammation to Post-Blemish Care

04 BOTANICAL ACTIVES ｜ GARDENIA FRUIT

Dried gardenia fruits (illustrative image)

INCI	Gardenia Jasminoides Fruit Extract
CAS	92457-01-7
Role in system	Inflammation axis · post-blemish care

Gardenia fruit extract (GJE)｜ Grade B　Significantly inhibited LPS-induced IL-1β, IL-6 and TNF-α release via TLR4／NKAP signaling downregulation, with anti-inflammatory activity validated in an in vivo zebrafish model (Exp Ther Med, 2021).

Geniposide (marker compound)｜ Grade B　Acts downstream of TLR4 to inhibit NF-κB p65 and MAPK pathways, exerting anti-inflammatory effects in animal inflammation models (Inflammation, 2014).

Crocetin (gardenia-derived active)｜ Grade B　In B16F10 melanoma cells it inhibited tyrosinase activity and melanin synthesis, downregulated tyrosinase and MITF proteins and scavenged ROS — pointing to the post-inflammatory hyperpigmentation (PIH) management chain (Anticancer Agents Med Chem, 2018).

Gardenia fruit’s “two-phase” value: acute and recovery
Acute phase (inflammation management)GJE / geniposide inhibit the TLR4–NF-κB／MAPK cascade, reducing IL-1β／IL-6／TNF-α release and easing the driving signals of redness and swelling.	Recovery phase (post-blemish care)Crocetin inhibits the tyrosinase–MITF axis and scavenges ROS, intervening upstream of melanin synthesis in the dark-mark formation chain (see Chapter 5).

Sources: Chen J, et al. Exp Ther Med. 2021;22(1):700. DOI:10.3892/etm.2021.10132; Song X, et al. Inflammation. 2014;37:1588-1598; Hashemi-Shahri S, et al. Anticancer Agents Med Chem. 2018 (Grade-B ingredient literature)

Stevia Leaf/Stem Extract: A Sweet Answer for Barrier and Soothing

04 BOTANICAL ACTIVES ｜ STEVIA

Stevia rebaudiana plant (illustrative image)

INCI	Stevia Rebaudiana Leaf/Stem Extract
CAS	91722-21-3
Role in system	Barrier · soothing · antioxidant

Stevioside (marker compound)｜ Grade B　At 250 μM in cell models, stevioside showed a triple “antioxidant + anti-inflammatory + barrier” effect:· Antioxidant: ↓ROS, ↓MDA; ↑T-SOD, ↑CAT, ↑GSH-Px;· Anti-inflammatory: ↓IL-6, ↓IL-8, ↓TNF-α; ↓NF-κB／IκB／ERK1/2 phosphorylation;· Barrier: ↑claudin-1, ↑occludin, ↑ZO-1 tight-junction proteins (Antioxidants, 2023).

Immunomodulatory support｜ Grade B　Stevioside activates AMPK and suppresses macrophage inflammatory responses (Molecules, 2021); 1 mM stevioside inhibited NF-κB in LPS-stimulated THP-1 cells (summarized in a 2023 review).

Why stevia is the “finishing ingredient” of the five-axis system: what anti-blemish formulas most often overlook is user experience and barrier consequences. With the highest typical value among the botanicals in the ingredient list (5%), stevia leaf/stem extract carries the soothing and barrier-support role: tight-junction upregulation directly answers the impaired-barrier fact of elevated TEWL in blemish-prone skin, closing the loop of “efficacy” and “mildness” within one formula.

Sources: Xu Q, et al. Antioxidants (Basel). 2023;12(5):1070. DOI:10.3390/antiox12051070; Wei F, et al. Molecules. 2021;26(4):858; content: AcneZero Ingredient List (Grade A)

05

Synergy · Claims · Applications

Translating ingredient evidence into market language: the synergy matrix, an evidence-graded claims system, the post-blemish care chain and application scenarios — every claim traceable to its source.

In this chapter ｜ 7 botanicals × 5 axes synergy matrix · Claims & evidence grading · Post-blemish care · Applications · B2B value

Seven Botanicals × Five Axes: The Synergy Matrix at a Glance

05 SYNERGY·CLAIMS·APPLICATIONS ｜ SYNERGY MATRIX

Ingredient	A1 Sebum	A2 Inflammation	A3 Oxidation	A4 Microbiome	A5 Barrier & soothing
Mahonia (berberine)	●	●	○	●
Salvia (tanshinones)		●	○	●
Silymarin	○	○	●	○	●
Olive leaf (polyphenols)	●	●	●
Bioflavonoids		●	●	○
Gardenia fruit (geniposide / crocetin)		●	○		●
Stevia (stevioside)		○	●		●

● Ingredient-level literature evidence for that axis (mainly Grade B; Grade-C extrapolation for olive leaf)　○ Indirect or auxiliary support (e.g., same-genus evidence, review support, associated endpoints in human studies)　—　The matrix summarizes the literature cited in Chapters 3–4; it is not the result of finished-product efficacy testing.

Matrix source: all ingredient literature cited in this material (see References); composition: AcneZero Ingredient List (Grade A).

The Claims System: Every Claim Has Its Evidence Coordinates

05 SYNERGY·CLAIMS·APPLICATIONS ｜ CLAIMS & EVIDENCE GRADING

Market claim (cosmetics framework)	Supporting logic	Key sources	Grade
Oil Control	Berberine inhibits FASN／DGAT1 and lipid secretion in sebocytes; olive leaf modulates SREBP-1／PPAR-γ (Grade-C extrapolation)	J Inflamm Res. 2025; CIMB. 2026	B／C
Blemish-Prone Skin Care	Berberine in vitro MIC／MBC, anti-biofilm and mouse-ear model; tanshinone antimicrobial review	Front Microbiol. 2023; Fitoterapia. 2025	B
Soothing	Quercetin, tanshinone IIA, gardenia fruit and stevioside inhibit the TLR–NF-κB cascade at multiple levels	See the evidence matrix in Chapter 3	B
Antioxidant Defense	Silymarin human study reduces lipid peroxidation; stevioside ↑antioxidant enzymes; flavonoid structure–activity relationship	JDD. 2024; Antioxidants. 2023	B
Microbiome Balance	Non-antibiotic, plant-derived antimicrobial strategy managing C. acnes overgrowth and biofilms	Front Microbiol. 2023	B
Barrier Support + Post-Blemish Tone Care	Stevioside upregulates tight-junction proteins; silymarin human study improves melanin index; crocetin inhibits tyrosinase	Antioxidants. 2023; J Cosmet Dermatol. 2023	B

Evidence grading: A = AcneZero’s own product data (MSDS safety, ingredient list); B = published ingredient literature (cell / animal / human, models as stated in the original papers); C = reasonable extrapolation from ingredient information. Finished-product efficacy verification is recommended before making finished-product claims.

Claim boundary: the above is a cosmetics efficacy narrative framework (blemish-prone skin care / oil control / soothing / microbiome balance / antioxidant / barrier & post-blemish tone care) and does not constitute drug or therapeutic claims.

The Post-Blemish Care Chain: Full Coverage from Inflammation to Dark Marks

05 SYNERGY·CLAIMS·APPLICATIONS ｜ POST-BLEMISH CARE

The formation chain of post-inflammatory hyperpigmentation (PIH) and its intervention points

Inflammatory cascade (IL／TNF-α) → Oxidative-stress amplification → Tyrosinase／MITF activation → Melanin deposition · dark marks

Intervention point ①: silymarin (human evidence)In a 4-week human study of a 0.5% silymarin serum (n=22), acne severity scores and lesion counts fell while the skin melanin index decreased significantly (J Cosmet Dermatol, 2023); a 2024 human study (n=56) reported improved post-inflammatory hyperpigmentation and reduced lipid peroxidation (J Drugs Dermatol, 2024).

Intervention point ②: crocetin (mechanistic evidence)Gardenia-derived crocetin inhibited tyrosinase activity and reduced melanin synthesis in B16F10 cells, downregulated tyrosinase and MITF protein expression and scavenged ROS — intervening upstream of melanin synthesis in dark-mark formation (Anticancer Agents Med Chem, 2018).

The complete narrative: inflammation management (Axis 2) reduces the upstream drive of PIH, antioxidant defense (Axis 3) blocks the amplification step, and silymarin plus gardenia provide human and mechanistic evidence for dark-mark care — AcneZero places “fighting acne” and “post-blemish recovery” within the same ingredient logic, giving brands a full-cycle product story from the acute phase to recovery.

Sources: Kim J, et al. J Cosmet Dermatol. 2023;22(2):561-568; J Drugs Dermatol. 2024;23(4). DOI:10.36849/JDD.8120; Hashemi-Shahri S, et al. Anticancer Agents Med Chem. 2018 (Grade-B ingredient literature)

Applications: From the Facial Core to Extended Scenarios

05 SYNERGY·CLAIMS·APPLICATIONS ｜ APPLICATIONS

Facial care (core scenario)	Body care	Scalp care (extended research direction)
· Blemish-care serum: the lead format for the full five-axis story· Oil-control lotion / gel: sebum management + microbiome balance· Soothing repair mask: inflammation management + barrier support· Post-blemish tone-care serum: the silymarin + gardenia PIH evidence chain· Targeted spot care: high-concentration multi-pathway positioning	· Back / chest blemish care: sebaceous-dense areas — a natural extension of the oil-control + microbiome narrative· Body mist / toner: water solubility suits large-area formats (Grade-A formula fact: water-soluble at 20°C)· Post-workout refreshing care: oil and microbiome management scenarios	· The scalp is likewise a sebum- and microbe-dominated ecosystem: Malassezia-mediated sebum peroxidation products (squalene monohydroperoxide, MDA) are among the triggers of dandruff (literature background)· AcneZero’s sebum-management, antioxidant and microbiome ingredient logic is mechanistically transferable to scalp scenarios· Positioning note: this is an extended research direction based on published literature; the MSDS defines the product’s use as a cosmetic skincare ingredient, and scalp applications require separate evaluation and validation

Formulation fit: the water-based (water-soluble) vehicle suits serums, toners, masks and gels; recommended pH, heat/light stability and specific compatibility parameters should be confirmed with the PuriPharm technical team — this material does not invent a recommended dosage.

Scalp background: DeAngelis YM, et al. J Investig Dermatol Symp Proc. 2005;10(3):295-297; product use and solubility: AcneZero MSDS v1.1 (Grade A).

B2B Partnership Value: A One-Stop, Multi-Pathway Anti-Blemish Solution

05 SYNERGY·CLAIMS·APPLICATIONS ｜ PARTNERSHIP VALUE

For brands: a complete science story	For formulators: clear engineering parameters	Regulatory & documentation support
· The five-axis mechanism + synergy matrix converts directly into product-page and detail-page storytelling· Every claim carries an evidence grade, standing up to regulatory and platform review· A full-cycle product-line imagination “from the acute phase to post-blemish recovery”	· Water-soluble (20°C), friendly to water-based formats· 4–25°C light-protected storage, routine supply-chain management· MSDS data showing no skin and no eye irritation, reducing the safety-assessment burden (Grade A)	· Listed in China’s Inventory of Existing Chemical Substances (IECIC)· Complete INCI / CAS information; transparent, traceable ingredient list· MSDS v1.1 and supporting technical documents for export and multi-market compliance assessment· The ingredient literature pack (References) supports claim filing and content review

CONTACT ｜ Business & Technical Inquiries

PuriPharm Co., Ltd.Web　www.puriactives.comEmail　service@puripharm.comTel　+86-572-2745768Address　7F, Building 6E, No. 1366 Hongfeng Road, Huzhou, Zhejiang, China

Product specifications and regulatory information: AcneZero MSDS v1.1 (Grade A); contact details: official company materials. Please contact the technical team for recommended dosage and finished-product efficacy verification plans.

References & Documentary Basis

REFERENCES

1. Cong TX, Hao D, Wen X, et al. From pathogenesis of acne vulgaris to anti-acne agents. Arch Dermatol Res. 2019;311(5):337-349. DOI:10.1007/s00403-019-01908-x
2. Dréno B, et al. Cutibacterium acnes and acne vulgaris: a brief look at the latest updates. J Eur Acad Dermatol Venereol. 2018;32(Suppl 2):5-14.
3. Condrò G, Sciortino R, Perugini P. Squalene peroxidation and biophysical parameters in acne-prone skin: a pilot “in vivo” study. Pharmaceuticals (Basel). 2023;16(12):1704. DOI:10.3390/ph16121704
4. Sun L, Yu Q, Peng F, et al. The antibacterial activity of berberine against Cutibacterium acnes: its therapeutic potential in inflammatory acne. Front Microbiol. 2023;14:1276383. DOI:10.3389/fmicb.2023.1276383
5. Berberine inhibits acne-related lipid secretion and inflammation by regulating the hsa-miR-3150a-3p/TP53 pathway. J Inflamm Res. 2025.
6. Lim HJ, Kang SH, Song YJ, et al. Inhibitory effect of quercetin on Propionibacterium acnes-induced skin inflammation. Int Immunopharmacol. 2021;96:107557. DOI:10.1016/j.intimp.2021.107557
7. A silymarin antioxidant serum improves facial acne alone and as part of a treatment regimen. J Drugs Dermatol. 2024;23(4). DOI:10.36849/JDD.8120
8. Kim J, et al. Efficacy and safety of silymarin containing antioxidant serum as an adjuvant treatment of mild-to-moderate acne vulgaris. J Cosmet Dermatol. 2023;22(2):561-568. DOI:10.1111/jocd.15439
9. Yoon JY, Kwon HH, Min SU, et al. Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P. acnes. J Invest Dermatol. 2013;133(2):429-440.
10. Kim J, Jo YW, Bang WJ, et al. Olive leaf extract suppresses sebogenesis and inflammation via AKT/ERK and SREBP-1/PPAR-γ signaling in human sebocytes. Curr Issues Mol Biol. 2026;48(6):549. DOI:10.3390/cimb48060549
11. Chen J, et al. Anti-inflammatory activities of Gardenia jasminoides extracts in retinal pigment epithelial cells and zebrafish embryos. Exp Ther Med. 2021;22(1):700. DOI:10.3892/etm.2021.10132
12. Song X, et al. Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice. Inflammation. 2014;37:1588-1598. DOI:10.1007/s10753-014-9885-2
13. Xu Q, et al. Stevioside improves antioxidant capacity and intestinal barrier function. Antioxidants (Basel). 2023;12(5):1070. DOI:10.3390/antiox12051070
14. Wei F, et al. Stevioside activates AMPK to suppress inflammation in macrophages. Molecules. 2021;26(4):858. DOI:10.3390/molecules26040858
15. Meng Z, Si CY, Teng S, et al. Tanshinone IIA inhibits lipopolysaccharide-induced inflammatory responses through the TLR4/TAK1/NF-κB signaling pathway in vascular smooth muscle cells. Int J Mol Med. 2019;43(4):1847-1858. DOI:10.3892/ijmm.2019.4100
16. Zhang T, et al. Tanshinone in acne therapeutics: integrating molecular mechanisms, drug development, and multimodal treatment strategies. Fitoterapia. 2025.
17. Yang X, Huang G, You L, et al. High-throughput RNA sequencing reveals the anti-inflammatory mechanism of baicalin on Propionibacterium acnes-induced acne in rabbits. J Tradit Chin Med Sci. 2019;6(3):201-210.
18. Bezáková L, et al. Lipoxygenase inhibition and antioxidant properties of bisbenzylisoquinoline alkaloids isolated from Mahonia aquifolium. Pharmazie. 1996;51(10):758-761.
19. Hashemi-Shahri S, et al. ROS-scavenging and anti-tyrosinase properties of crocetin on B16F10 murine melanoma cells. Anticancer Agents Med Chem. 2018.
20. Mezei M, Gulasekharam V. Liposomes — a selective drug delivery system for the topical route of administration: gel dosage form. Life Sci. 1980;26:1473-1477.
21. Li H, et al. Oleuropein and hydroxytyrosol as skin-permeable elastase/collagenase inhibitors with synergistic antioxidant activity in human skin fibroblasts. Int J Food Sci Nutr. 2022;73(4):460-470.
22. DeAngelis YM, et al. Three etiologic facets of dandruff and seborrheic dermatitis: Malassezia fungi, sebaceous lipids, and individual sensitivity. J Investig Dermatol Symp Proc. 2005;10(3):295-297.
23. Zhang DQ, Tai JX, Fu Q. Research and application of bioflavonoids. Food and Fermentation Industries. 1999;25(6):52-57. (In Chinese)
24. Liao ZJ. Process for extracting and refining berberine from Mahonia. Chinese patent CN1069493A, published 1993-03-03. (In Chinese)

Internal company documents (Grade-A factual basis): PuriPharm AcneZero MSDS v1.1 (2019-07-13); AcneZero Ingredient List.

From single-target anti-acneto multi-pathway blemish-prone skin management.

PuriActives® AcneZero — Seven botanicals × phospholipid-based active system × five axes

PuriPharm Co., Ltd. ｜ INNOVATION FOR HEALTH & BEAUTYwww.puriactives.com ｜ service@puripharm.com ｜ +86-572-2745768 ｜ Huzhou, Zhejiang, China

PuriActives® Sodium Trehalose Sulfate 10%

Beyond Hydration · Barrier Biology

TECHNICAL PRODUCT PRESENTATION

PuriActives® Sodium Trehalose Sulfate 10%

From Hydration to Activation of the Skin’s Own Moisturizing Barrier

Beyond Hydration · Barrier Biology

INCI NAME: SODIUM TREHALOSE SULFATEPuriPharm Co. Ltd.

RETHINKING HYDRATION

Moisturization Is More Than Adding Water to Skin

CLASSICAL MOISTURIZATION: WATER FROM OUTSIDE

Humectant: draws water from the environment or deeper layersEmollient: softens the stratum corneum and improves skin feelOcclusive: forms a film and reduces evaporationAll three add or retain water, but do not directly build the skin’s own moisturizing system.

BARRIER BIOLOGY: HELPING SKIN MANAGE WATER

01 Keratinocyte differentiation and cornification02 Epidermal lipid transport (ABCA12)03 Ceramide barrier organization04 Filaggrin (FLG) metabolism05 Natural moisturizing factor (NMF) production

PuriActives® Sodium Trehalose Sulfate moves from external hydration toward support for the skin’s endogenous moisturizing system.

PRODUCT IDENTITY

PuriActives® Sodium Trehalose Sulfate 10%

Chemical structure of sodium trehalose sulfate, Maeda et al., 2024

Item	Information
INCI NAME	SODIUM TREHALOSE SULFATE
Ingredient category	Low-molecular-weight sulfated disaccharide active
Functional positioning	Moisturizing active · barrier-care active · skin-conditioning active
Molecular feature	Mol.Wt. ≈ 694 (tri- or tetra-sulfated)

Trehalose backbone

↓

Sulfation

↓

Sodium salt

Sulfation differentiates it from ordinary trehalose, transforming a sugar into a barrier-active molecule.

WHY SULFATION

Trehalose Is Only the Starting Point: Sulfation Changes Biological Behavior

Trehalose

Sodium trehalose sulfate

Key comparisons in the Maeda study

• Unsulfated trehalose did not produce the same complete barrier-gene expression response as sodium trehalose sulfate.
• In a 3D epidermal-model TEWL test, the trehalose group did not differ significantly from control, while the sodium trehalose sulfate group showed a significant reduction.
• Low-molecular-weight sulfated disaccharides below 1,000 Da can act on stratum-corneum barrier function.

3D epidermal-model TEWL (g/cm²·h): only the sulfated-sugar group was significantly lower than control, *p<0.05.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666. Chemical structures reproduced from Figure 2.

THREE PILLARS OF THE BARRIER

An Effective Barrier Depends on Three Coordinated Systems

Cornified Envelope

IVL · TGM1

Intercellular Lipids

ABCA12 · Ceramide

Natural Moisturizing Factors

FLG · CASP14 · CAPN1 · BLMH

Sodium trehalose sulfate is supported by evidence across all three systems.These systems determine the “bricks” of the stratum corneum, the “mortar” between them, and water storage within the bricks.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666.

MECHANISM OVERVIEW

One Molecule, Multiple Pathways to Strengthen the Moisturizing Barrier

After topical application, sodium trehalose sulfate participates in epidermal biological regulation:

01 IVL / TGM1 ↑

Cornified-envelope formation ↑

02 ABCA12 ↑

Lamellar-granule lipid transport ↑Ceramide-barrier organization ↑

03 FLG / CASP14 / CAPN1 / BLMH ↑

Free amino acids ↑Natural moisturizing factors (NMF) ↑

All three pathways converge on: barrier integrity ↑ · stratum-corneum hydration ↑ · transepidermal water loss (TEWL) ↓

Evidence chain: qPCR gene expression · immunofluorescence protein validation · free-amino-acid measurement · 3D-model TEWL · four-week double-blind human study

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666.

LIPID TRANSPORT · ABCA12

ABCA12 Enables the Skin to Transport Its Own Barrier Lipids

ABCA12 is a key lipid transporter in keratinocytes. This ATP-binding cassette transporter loads intracellular lipids into lamellar granules and delivers them to the stratum corneum.

Intracellular lipid synthesis

↓

Loading into lamellar granules

↓

Release of intercellular lipids in the stratum corneum

↓

Formation of a complete barrier-lipid structure

This supports the endogenous epidermal lipid-transport system rather than merely adding lipids from outside.

Relative ABCA12 mRNA expression in a 3D epidermal model, *p<0.05 vs. control.

ABCA12 immunofluorescence: stronger signal in the sodium trehalose sulfate group, 3D epidermal model.

Sources: Maeda K, et al. Skin Res Technol. 2024;30:e13666; Sakai K, et al. Exp Dermatol. 2007;16:920–926.

CERAMIDE-RICH BARRIER

From ABCA12 to a Ceramide-Rich Barrier

ABCA12 ↑

↓

Lipid loading and transport ↑

↓

Lamellar granules

↓

Intercellular lipids

↓

Ceramide-rich barrier

Immunofluorescence validation: stronger ceramide signal

Control, left; sodium trehalose sulfate treatment, right

In a 3D epidermal model, the sodium trehalose sulfate group showed stronger ceramide immunofluorescence than the vehicle control, suggesting support for the organization of intercellular barrier lipids in the stratum corneum.

Why it matters: Ceramides are core components of stratum-corneum intercellular lipids and determine barrier density. When ABCA12 function is impaired, lamellar-granule lipids decline and structural barrier defects emerge. Supporting ABCA12 supports the skin’s own lipid supply chain.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 5C.

FILAGGRIN · NMF PATHWAY

Activating the Skin’s Natural Moisturizing Factor Pathway

Pathway by which FLG is degraded in the granular layer and stratum corneum to generate NMF, Maeda et al., 2024, Figure 1.

Profilaggrin in the granular layer

↓

Filaggrin (FLG)

↓

FLG processing and degradation: CASP14 / CAPN1 / BLMH

↓

Free amino acids

↓

Natural moisturizing factors (NMF)

↓

Stratum-corneum hydration

This is the skin’s own moisturizing system, not water supplied from outside.

Sources: Maeda K, et al. Skin Res Technol. 2024;30:e13666; Hoste E, et al. J Invest Dermatol. 2011;131:2233–2241.

MULTI-GENE BARRIER RESPONSE

One Intervention Activates Seven Barrier-Related Pathways

3D epidermal-model qPCR: all seven mRNA markers were significantly upregulated by sodium trehalose sulfate, *p<0.05, **p<0.01 vs. control; n=3.

IVL Involucrin ↑

TGM1 Transglutaminase 1 ↑

ABCA12 Lipid transport ↑

FLG Filaggrin ↑

CASP14 ↑

CAPN1 ↑

BLMH ↑

The response covers cornified-envelope formation, lipid transport and NMF production rather than a single target.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 4.

PROTEIN-LEVEL EVIDENCE

From Gene Expression to Barrier Structure

TGM1

Control, left; STS treatment, right

ABCA12

Control, left; STS treatment, right

Ceramide

Control, left; STS treatment, right

FLG

Control, left; STS treatment, right

In 3D epidermal-model immunofluorescence, the sodium trehalose sulfate group showed greater fluorescence intensity and distribution area for TGM1, ABCA12, ceramide and FLG than the vehicle control. The evidence therefore extends beyond mRNA changes to proteins and barrier structure.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 5.

FREE AMINO ACIDS · NMF SOURCE

Increasing the Source Materials for Natural Moisturizing Factors

Free amino acids / total amino acids, %, 3D epidermal model, n=4; *p<0.05, **p<0.01 vs. control.

Significant increases from 0.05% to 0.20%: the 0.05%, 0.10% and 0.20% STS solution groups were all higher than control.

Free amino acids are core components of natural moisturizing factors and arise from filaggrin degradation. After sodium trehalose sulfate treatment, the free-amino-acid ratio in the 3D epidermal model was significantly higher than control.

It not only attracts water, but also supports the skin in producing its own natural moisturizing factors.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 6.

IMMEDIATE HYDRATION

Visible Improvement in Stratum-Corneum Water Content from 15 Minutes

Short-term human forearm test: change in stratum-corneum water content, ΔμS, 15 / 30 min; n=5; *p<0.05, **p<0.01 vs. control.

15 min

An increase in water content was already observed.

30 min

The improvement persisted and remained significant.

After treatment with 0.05%, 0.1% and 0.2% sodium trehalose sulfate solutions, stratum-corneum water content was significantly higher than with the water control. The comparison 0.3% heparinoid emulsion was significant only at 15 minutes and no longer differed significantly from control at 30 minutes.

Immediate hydration and support for endogenous moisturization can be achieved together.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 7A.

TEWL · BARRIER EFFICIENCY

Reducing Water Loss and Improving Barrier Efficiency

3D epidermal-model TEWL, g/cm²·h, three days after treatment; n=3; *p<0.05 vs. control.

Transepidermal water loss is a core measure of skin-barrier integrity. Lower TEWL indicates a stronger ability to retain water. All three sodium trehalose sulfate concentration groups had significantly lower TEWL than control.

ABCA12 + ceramide + TGM1 / IVL

↓

Barrier integrity ↑

↓

Water loss ↓

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 7B.

HUMAN STUDY DESIGN

Four-Week Randomized Double-Blind Human Study

Randomized

Random allocation

Double-blind

Double-blind design

Placebo-controlled

Placebo control

4 Weeks

Continuous facial use

Item	Study information
Participants	Included in statistical analysis: active group n=13; placebo group n=11
Test formulations	Active group: toner and emulsion containing 0.05% sodium trehalose sulfate; placebo group: visually matched blank formulations
Use	Twice daily, morning and evening, for four weeks
Primary endpoints	TEWL and stratum-corneum water content
Ethics and enrollment	Conducted according to the Declaration of Helsinki and approved by an ethics committee, protocol HENM21083001, 1 October 2021; 26 women aged 33–59 enrolled

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666.

4-WEEK CLINICAL RESULTS

Four Weeks of Use Improved Hydration and Barrier Function Together

TEWL, g/m²·h: active-group mean W0→W4, 17.3→16.1; between-group comparison of ΔTEWL, p<0.01.

Stratum-corneum water content, μS: active group 81.3→105.5, p<0.01; between-group comparison of change, p<0.05.

Significant TEWL improvement

Active group Δ −1.2 vs placebo group Δ +3.2

Significant increase in stratum-corneum water content

Active group Δ +24.2 vs placebo group Δ +4.2

Significant between-group differences

Both core endpoints favored the active group

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figures 8A and 8B; n=13 active / n=11 placebo.

HYDRATION + CLARITY

A Healthy Barrier Can Also Improve the Look of Skin

Blood oxygenation index: increased after four weeks in the active group; between-group comparison of change, p<0.05.

Melanin index: decreased after four weeks in the active group; between-group comparison of change, p<0.05.

The paper also observed improvements in tone-related measures: blood oxygenation index ↑ and melanin index ↓.

These were accompanying observational endpoints in the four-week human study and do not support a strong whitening claim.

Suggested marketing language: improves dry, dull appearance · enhances a hydrated, translucent look · supports a more even, healthy-looking skin tone · provides barrier and hydration support for brightening products

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figures 8C and 8D.

DRY & SENSITIVE SKIN

Breaking the Barrier Damage–Dryness–Sensitivity Cycle

Barrier disruption

↓

TEWL ↑

↓

Dehydration

↓

Roughness and tightness

↓

Environmental sensitivity

↓

Further barrier disruption

Where sodium trehalose sulfate acts

Barrier: supports the cornified envelope and barrier integrityLipids: supports endogenous lipid transport and ceramide organizationNMF: supports natural moisturizing factor productionHydration: increases stratum-corneum water content and reduces TEWL

Suitable product concepts

Dry-skin care · sensitive-skin barrier care · seasonal-transition careMature dry skin · companion care for high-activity products such as retinoids and acidsPost-cleansing tightness care

SCALP IS SKIN

The Scalp Also Needs an Intact Barrier

The scalp is an extension of the skin and similarly depends on:

• Stratum-corneum structure and the cornified envelope
• Intercellular lipids and ceramides
• Natural moisturizing factors and water balance

When the scalp barrier is impaired: dryness · tightness · discomfort · flaking · reduced quality of hair appearance

PuriActives® Sodium Trehalose Sulfate can extend to: scalp serum · hair tonic · shampoo · conditioner · scalp mask · leave-on scalp essence

SULFATED SACCHARIDES PLATFORM

Sulfated Saccharides: an Emerging Scalp and Hair Research Platform

This page concerns platform research on sulfated saccharides. It is not human hair-growth clinical evidence for sodium trehalose sulfate.

US 5,618,798: hair and scalp applications of sulfated saccharides

The patent covers topical use of sulfated monosaccharides, disaccharides and oligosaccharides in hair and scalp applications, including shampoo, hair tonic, hair conditioner, gel, emulsion and lotion formats.

Positioning of this page: scalp moisture + barrier + hair environment. The focus is scalp moisturization and barrier care, not pharmaceutical hair-growth promotion.

Supporting studies on sulfated saccharides:

• US 4,912,093: synthetic sulfated saccharides and wound care
• WO 1989/05646: sulfated saccharides and inflammatory skin care
• US 5,605,938: sulfated anionic polymers and cellular mechanisms
• FR 2877565: dextran sulfate and soothing applications
• Toyama S, et al. 2025: topical OJI-204 for skin dryness and dryness-induced itching, Biomedicines. 2025;13:556

FORMULATION APPLICATIONS

Highly Flexible Applications from Serums to Scalp Care

SKIN CARE

TonerEssence / serumAmpouleLotion / creamMaskEye careSensitive-skin care

HAIR & SCALP

ShampooConditionerScalp serumHair tonicScalp sprayHair mask

As a water-soluble, low-molecular-weight active, it is suitable for aqueous products, serums, emulsions, rinse-off scalp products and leave-on scalp products.

FORMULATION DESIGN

Building the Next Generation of Barrier-Moisturizing Systems

STS + Hyaluronic Acid

Immediate water retention + support for the endogenous moisturizing system

STS + Ceramide

Endogenous lipid transport + exogenous lipid supplementation

STS + Panthenol

Barrier support + soothing care

STS + Ectoin

Environmental-stress care

STS + Niacinamide

Multidimensional barrier care

STS + Amino Acid / NMF Complex

Endogenous NMF generation + exogenous NMF supplementation

These formulation-design suggestions are based on complementary mechanisms. Actual performance of each combination requires validation in the specific formulation.

DOSE TRANSLATION

A 10% Active System Connected to the Published Human-Study Dose

PuriActives® Sodium Trehalose Sulfate 10%: 10% active content in the ingredient

↓

Recommended finished-formula addition: 0.50%

↓

Actual sodium trehalose sulfate concentration in the formula: 0.05%

This directly corresponds to the 0.05% active concentration used in the human study by Maeda et al.

Studies at this concentration included a four-week randomized double-blind placebo-controlled human trial showing improvements in TEWL and stratum-corneum water content, a short-term human hydration test, and validation of genes, proteins and free amino acids in a 3D epidermal model.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666.

WHY PURIACTIVES®

PuriActives® Sodium Trehalose Sulfate 10%

01 Barrier biology

ABCA12 / TGM1 / IVLSupports the cornified envelope and endogenous lipid transport

02 Endogenous moisturization

FLG / NMF / free amino acidsSupports the skin in producing its own moisturizing factors

03 Human validation

Four-week randomized double-blind studyTEWL ↓ · stratum-corneum water content ↑

04 Dual-scenario application

Skin + scalpOne platform for skin and scalp care

Lasting moisturization means more than bringing water into the skin. It also means helping the skin manage its own water.

REFERENCESMaeda K, Zhou Z, Guo M, Zhang J, Chen L, Yang F. Functional properties and skin care effects of sodium trehalose sulfate. Skin Res Technol. 2024;30:e13666. doi:10.1111/srt.13666Hoste E, et al. J Invest Dermatol. 2011;131:2233–2241. · Denecker G, et al. Nat Cell Biol. 2007;9:666–674. · Sakai K, et al. Exp Dermatol. 2007;16:920–926.Supporting platform research on sulfated saccharides: US 4,912,093 · US 5,618,798 · WO 1989/05646 · US 5,605,938 · FR 2877565 · Toyama S, et al. Biomedicines. 2025;13:556.

PuriPharm Co. Ltd.www.puriactives.com · service@puripharm.com+86-572-2745768 · Building 6, No. 1366 Hongfeng Road, Huzhou, Zhejiang, ChinaPuriActives® is a registered trademark of PuriPharm Co., Ltd. This material introduces a cosmetic ingredient.

PuriActives® BioCalmin

Precision Molecular Soothing for Sensitive Skin & Scalp

PURIPHARM CO. LTD. — COSMETIC ACTIVE INGREDIENTS

PuriActives® BioCalmin

Precision Molecular Soothing for Sensitive Skin & Scalp

INCI: Hydroxyphenyl Propamidobenzoic AcidScientific name: Dihydroavenanthramide D (DHAvD), nature-inspired synthetic avenanthramide

Nature-Inspired Chemistry · Fast Comfort · Multi-Pathway Defense

THE CHALLENGE — SKIN BIOLOGY

When Skin Overreacts, Multiple Signals Converge

COMMON MANIFESTATIONS：Itching、Redness、Burning、Stinging、Tightness、Dryness、Irritation、Scalp discomfort

POTENTIAL TRIGGERS：SurfactantsEnvironmental stress、Dry skin、Shaving、Hair coloring、Bleaching、Exfoliating acid、Retinoids、Frequent cleansing、Compromised skin barrier

THE SIGNALING CASCADE — SCHEMATIC

External Stress

↓

Sensory Nerve Activation · Substance P

↓

Mast Cell Activation

↓

Histamine + Inflammatory Mediators

↓

Itch · Redness · Discomfort

One trigger can set off the full neurogenic irritation chain — effective soothing starts upstream.

THE MOLECULE

Nature-Inspired Precision Chemistry

Dihydroavenanthramide D (DHAvD) | MW ≈ 285.3 Da | logP ≈ 3.34

Item	Information
INCI NAME	Hydroxyphenyl Propamidobenzoic Acid
SCIENTIFIC NAME	Dihydroavenanthramide D (DHAvD)
INGREDIENT FAMILY	Nature-inspired synthetic avenanthramide

A synthetic analogue nature-inspired by oat avenanthramides — the phenolic anthranilic acid amides behind the protective chemistry of oats — engineered as a highly defined molecular active with consistent, reproducible performance.

Key actions

Anti-itchAnti-rednessAnti-histamine pathway

Product attributes

AntioxidantEffective at low concentrationsSkin & scalp soothing

Molecular properties per published pharmaceutical-formulation research on DHAvD. Highly defined molecular identity — not an oat extract. Activity at low concentrations, across both skin and scalp applications.

DESIGN LOGIC

From Oat Defense Chemistry to Targeted Cosmetic Soothing

Avenanthramides are anthranilic acid amides known for biological activities relevant to skin comfort. PuriActives® BioCalmin translates that biology into one defined, reproducible molecule.

Oat Avenanthramide Biology

↓

Structure–Activity Understanding

↓

Dihydroavenanthramide D

↓

Consistent Molecular Soothing Performance

MOLECULAR ADVANTAGES

Controlled molecular identityReproducible quality, batch after batchStrong activity at ppm-level concentrations

MULTIFUNCTIONAL ADVANTAGES

Multifunctional soothing profileAntioxidant capacityBroad formulation potential

Nature-Inspired. Molecularly Defined.The premium positioning — beyond “naturalness”: defined, reproducible, potent.

MECHANISM

One Molecule. Four Levels of Skin Comfort.

NET RESULT: Less Itch · Less Redness · Less Irritation · More Comfort

01 Substance P / Mast Cell Pathway

Helps inhibit Substance P-induced histamine release from mast cells.

02 Histamine-Related Itch & Redness

Helps reduce downstream itch and erythema responses in challenged skin.

03 Inflammatory Signaling

Published mechanistic research supports modulation of NF-κB-related inflammatory signaling.

04 Oxidative Stress

Strong radical-scavenging activity helps limit the oxidative amplification of irritation.

MECHANISM IN FOCUS

Interrupting the Substance P–Mast Cell–Histamine Axis

Sensory Nerve

↓

Substance P

↓

Mast Cell

↓

Histamine

↓

Itch · Redness

PuriActives® BioCalmin inhibits Substance P-induced histamine release.

Substance P released from sensory nerves stimulates mast cells and promotes histamine release, driving itching, redness and neurogenic skin discomfort. Published studies show that synthetic avenanthramides including Dihydroavenanthramide D inhibit Substance P-induced histamine release from mast cells; the original patent literature describes anthranilic acid amides for precisely this purpose.

Target the Signal Before It Becomes Visible Discomfort.

Evidence type: in vitro mast-cell assay; patent literature.

EVIDENCE — IN VITRO

Strong Activity at ppm-Level Concentrations

−81%histamine net release at 500 ppm DHAvD vs. stimulated control

Published in-vitro mast-cell results show progressive, dose-dependent suppression of histamine net release as DHAvD concentration rises from 0.5 to 500 ppm — potent activity well below typical use levels.

Histamine net release relative to Substance P-stimulated control (= 100%). Chart redrawn from published data.Source: Schmaus G, Herrmann M, Joppe H, Lange S, Koch O, Pillai R, Röding J. Dihydroavenanthramide D for Anti-irritant and Anti-itch. Cosmetics & Toiletries. 2007;122(11):55–66.

EVIDENCE — HUMAN IN VIVO

From Mast Cells to Human Skin

HUMAN IN VIVO — HISTAMINE CHALLENGE	STUDY DESIGN
Method	Double-blind, placebo controlled
Challenge	Histamine challenge (skin-prick model)
Subjects	≈ 10 subjects per study
Formulations	O/W emulsions with 500 ppm synthetic avenanthramides
Controls	Placebo & untreated controls
Assessment	Itch and redness scoring up to 180 minutes

Itch Reduction

significantly lower vs placebo — p < 0.05

Redness Reduction

significantly lower vs placebo — p < 0.05

Schematic representation of the published outcome — synthetic avenanthramides including Dihydroavenanthramide D significantly reduced histamine-induced itch and redness versus placebo and untreated skin; bar heights are illustrative, not original quantitative values. Source: Schmaus G, et al. Cosmetics & Toiletries. 2007;122(11):55–66.

Visible Redness Down. Perceived Itch Down.

POTENCY

Powerful Soothing Does Not Require High Loading

500 ppm

= 0.05% active

The concentration that demonstrated meaningful anti-itch and anti-redness activity in the published human histamine-challenge model.

High biological potency

Meaningful activity at a low concentration.

Efficient formulation concept

Supports efficient formulation design.

Attractive in sophisticated sensitive-skin formulations

Suitable for advanced sensitive-skin products.

Compatible with multi-active cosmetic systems

Can be integrated into multi-active systems.

Published active concentration for Dihydroavenanthramide D (Schmaus G, et al. 2007). Final PuriActives® BioCalmin use level and assay: refer to the current PuriPharm TDS / SPEC.

EVIDENCE — ANTIOXIDANT

Soothing + Radical Defense

ABTS ANTIOXIDANT ASSAYIC50 = 26.54 μMIC50 = 7.57 μg/mL

Published ABTS data report radical-scavenging activity for DHAvD comparable with the reference antioxidants α-tocopherol and Trolox under the same assay conditions.

• Helps neutralize reactive radicals
• Helps reduce oxidative amplification of irritation
• Supports environmental-stress protection concepts
• Complements sensitive-skin and healthy-aging formulations

Calm Today. Defend Against Tomorrow’s Stress.

Source: Schmaus G, et al. Dihydroavenanthramide D for Anti-irritant and Anti-itch. Cosmetics & Toiletries. 2007;122(11):55–66.

MECHANISTIC CONTEXT

Beyond Histamine: Supporting Control of the Inflammatory Cascade

ROS / Cytokine Stress

↓

IκB degradation

↓

NF-κB Activation

↓

Inflammatory Mediator Expression

Published mechanistic studies on DHAvD demonstrate suppression of NF-κB-related signaling and downstream iNOS / NO responses in experimental biological models — a second, histamine-independent layer of the molecule’s soothing logic.

How to read this evidence: Supporting mechanistic evidence — not a direct clinical skin-efficacy claim. The experimental disease model in the source publication is not a product indication.

MECHANISTIC STUDY — NF-κB · iNOS · NOReference: Lv N, Song MY, Lee YR, et al. Biochem Biophys Res Commun. 2009;387(1):97–102.

MOLECULAR ROBUSTNESS

Stable Across a Remarkably Broad pH Window

Broad pH stability expands formulation possibilities.

pH 3　—　pH 5　—　pH 7　—　pH 9　—　pH 12

acidicalkaline

Published stability research evaluated DHAvD at pH 3 · 5 · 7 · 9 · 12 over 24 weeks and reported only slight degradation — even under very acidic and very alkaline conditions.

24 weeks of stability evaluation

WHERE BROAD pH STABILITY MATTERS

Facial skin careCleansing productsShaving products

MORE APPLICATIONS

Scalp productsHair coloring systemsBleaching-associated comfort concepts

Molecule-level stability data (published research; Schmaus G, et al. 2007). Final product pH range and handling: current PuriPharm TDS / SPEC.

FORMULATION SCIENCE

Unlocking Dermal Availability Through Smart Vehicle Design

Vehicle design determines how much DHAvD reaches viable skin.

EX VIVO HUMAN SKIN — FRANZ DIFFUSION

• 2–4× higher DHAvD release within 30 minutes with a 2% butylene glycol / pentylene glycol blend
• ≈ 2× penetration into viable skin layers within 30 minutes
• Sustained delivery advantage maintained over 300 minutes

41% vs 12% of the applied dose, optimized vs reference formulation.

Published formulation science using Dihydroavenanthramide D. Source: Heuschkel S, Wohlrab J, Schmaus G, Neubert RHH. Eur J Pharm Biopharm. 2008;70(1):239–247. doi:10.1016/j.ejpb.2008.04.005

SCALP CARE

Sensitive Scalp Is Sensitive Skin

WHAT SENSITIVE SCALP FEELS LIKE

Itching · Burning · Redness · Dryness · Tightness · Dandruff-associated discomfort · Irritation after coloration or bleaching

WHERE BIOCALMIN FITS

Scalp soothing tonicsSensitive-scalp shampoosAnti-dandruff shampoosScalp serums

MORE APPLICATIONS

Dry-scalp treatmentsHair-color aftercareBleaching / perming comfortDaily scalp care

Comfort Starts at the Scalp.

EVIDENCE — CLINICAL SCALP STUDY

Noticeable Scalp Comfort in 30 Minutes

−57%

scalp itch vs. placebo

after 30 minutes · single application · p < 0.05

CLINICAL SCALP STUDY	Information
Participants	18 volunteers with itchy scalp
Test formulation	1% tested same-active formulation
Design	Single application, placebo controlled
Evaluation	30-minute evaluation

Relative scalp itch (placebo = 100%).

Source: Published same-active scalp clinical study; n = 18; 30-minute single-application evaluation. Chart redrawn in the PuriPharm visual system.

EVIDENCE — CLINICAL SCALP STUDY

Immediate Comfort. Sustained Performance.

CLINICAL SCALP STUDY — 5 DAYS−40% itching vs. baseline after five days−47% itching vs. placebo after five days

The same study reported a marked reduction in burning sensation.

−40% vs baseline

−47% vs placebo

From Fast Relief to Daily Scalp Comfort

18 volunteers with itchy scalp · once-daily use · 5-day treatment · placebo comparison · symptom scores for itching and burning. Published same-active scalp clinical study; charts redrawn from reported results.

SCALP CARE — COMBINATION CONCEPT

Go Beyond Flake Control

Anti-Dandruff Active + Dihydroavenanthramide D

↓

Flake Management + Itch Comfort

Published patent literature reports combinations of DHAvD with climbazole for itchy scalp and anti-dandruff applications. Human studies described in the patent showed improved itch reduction when the two actives were combined — the anti-dandruff active manages flakes while DHAvD addresses the itch signal.

0.05% DHAvD + 0.2% ClimbazoleSynergy index 0.77synergistically enhanced itch-relieving activity in the patent dataset

APPLICATIONS: Anti-dandruff shampoo · Anti-dandruff scalp serum · Scalp lotion · Itchy dry-scalp products

PATENT REFERENCES:WO2004047833A2 — Anthranilic acid amides and derivatives thereof as cosmetic and pharmaceutical agents (2004)WO2007062957A1 / EP1959915B1 / US8911795B2 — Anthranilic acid amide + anti-dandruff active combinations for itch relief (2007)

APPLICATIONS — SKIN CARE

High-Performance Soothing Across Skin-Care Categories

Add Comfort Without Compromising Performance.

SENSITIVE SKIN

Sensitive-skin serumSoothing essenceRedness-care creamDaily comfort moisturizerSensitive body lotion

HIGH-ACTIVITY SKIN CARE

Retinoid companion careAHA / BHA / PHA formulationsBrightening systemsPost-exfoliation careAdvanced anti-aging formulas

STRESS & RECOVERY

After-sunAfter-shavePost-cleansing comfortDry, itchy-feeling skin careMask formulationsEnvironmental-stress products

APPLICATIONS — HAIR & SCALP

A Dedicated Soothing Strategy for Modern Scalp Care

APPLICATION CONCEPTS

Sensitive scalp shampooScalp soothing tonicAnti-dandruff shampooAnti-dandruff serumDry scalp care

MORE FORMATS

Scalp essencePost-hair-color carePost-bleaching comfortRelaxing / straightening aftercareLeave-on scalp spray

CORE BENEFIT ARCHITECTURE

Anti-ItchAnti-RednessScalp ComfortAnti-Dandruff SupportPost-Chemical-Treatment Soothing

From sensitive-skin care to advanced scalp comfort — one molecule, two territories.

WHY PURIACTIVES® BIOCALMIN

Calm the Signal. Restore the Comfort.

PuriActives® BioCalmin — Hydroxyphenyl Propamidobenzoic Acid. A precision molecule for next-generation soothing formulations, from sensitive-skin care to advanced scalp comfort.

FAST

Rapidly helps relieve itch and discomfort.

TARGETED

Acts on the Substance P–mast cell–histamine pathway.

PROVEN

Supported by human, cellular and formulation research.

MULTIFUNCTIONAL

Soothing + redness care + antioxidant defense.

VERSATILE

Designed for advanced skin and scalp concepts.

NanoActive™ SA Nano-encapsulated Salicylic Acid

Precision purification, from pores to scalp

NEXT-GENERATION SALICYLIC ACID DELIVERY

NanoActive™ SA | Nano-encapsulated Salicylic Acid

Precision purification, from pores to scalp

Powered by PURISOME® FlexVes™ Liposome Technology

INCI: Salicylic Acid

POSITIONING

Proven salicylic acid efficacy × advanced nanoliposomal delivery

NanoActive™ SA combines the well-established biological value of salicylic acid with PuriPharm’s proprietary nano-delivery platform, offering a more formulation-friendly, skin-compatible and targeted solution for modern cosmetic formulations.

Classic salicylic acid, scientifically validated

Keratin renewal and normalized desquamationComedolytic action and follicular decongestionSebum and blemish management

PURISOME® nanoliposomal delivery

Water-phase friendlyControlled, sustained deliveryPotential for follicular targeting

Face care · Body care · Scalp and hair care

MODERN SKIN & SCALP CHALLENGES

Oily skin and scalp: persistent, recurring concerns

Recurring concerns

01 Visibly enlarged pores02 Excess keratin buildup03 Blackheads and whiteheads04 Rough, uneven texture05 Shine and dullness06 Recurrent pore congestion07 Scalp oil and adherent flakes

What determines the appearance of visible pores?

Keratin buildup within folliclesLevel of sebum productionStructural visibility of follicular openingsSkin surface texture

Pore appearance = keratin × sebum × structure × texture

Pore concerns are multifactorial. This limits purely astringent approaches and provides a clear scientific entry point for actives that manage keratinization.

THE CLASSIC ACTIVE

Salicylic acid: an enduring classic in skin science

Salicylic Acid · C₇H₆O₃

INCI: Salicylic AcidType: aromatic hydroxy acid (BHA), pKa ≈ 3.0Properties: lipophilic, with affinity for sebum-rich and follicular environments; limited solubility in water at room temperature.

01 Aromatic hydroxy-acid structure

The benzene ring and ortho hydroxyl and carboxyl groups determine its distinctive physicochemical behavior.

02 Lipophilicity

Unlike water-soluble AHAs, it can enter sebum-rich follicular environments.

03 Affinity for the pilosebaceous unit

It can act where comedones and blemishes originate.

04 Activity within the stratum corneum

It acts on connections between corneocytes without requiring deep penetration.

Its molecular properties give salicylic acid a distinctive role in pore and follicular care.

MECHANISM 01 · DESMOLYTIC ACTION

Mechanism 1: desmolysis regulates cohesion rather than “dissolving keratin”

Modern skin science holds that salicylic acid disrupts intercellular connections and reduces corneocyte cohesion, allowing abnormally accumulated keratin to shed in an orderly manner rather than simply “dissolving keratin.”

Densely accumulated stratum corneum

↓

Reduced corneocyte cohesion

↓

Normalized desquamation

↓

Smoother skin surface

Formulation relevance: Desmolysis rather than aggressive peeling supports keratin management with a lower burden. This biology underpins applications for oily skin, pores, blemishes and the scalp.

MECHANISM 02 · COMEDOLYTIC ACTION

Mechanism 2: comedolytic action along the follicular pathway

Comedone formation cascade

Hyperkeratinization

↓

Follicular opening blockage

↓

Microcomedone

↓

Blackhead / whitehead

↓

Inflammatory lesion

① Normalized desquamation

Corrects hyperkeratinization at the follicular opening and reduces blockage at its source.

② Lipophilic penetration

Moves through the sebum-rich environment into the follicle instead of remaining on the surface.

③ Reduced cellular buildup

Decreases abnormal accumulation of keratinocytes within the follicle.

④ Comedolysis

Helps clear established blockages and improve blackheads and whiteheads.

Effective comedone management depends on keratinization within the follicle, not only surface cleansing. Salicylic acid’s lipophilicity gives it this distinctive position.

Mechanism review: Arif T. Clin Cosmet Investig Dermatol. 2015;8:455–461.

MECHANISM 03 · INFLAMMATION & BLEMISH BIOLOGY

Mechanism 3: the inflammatory dimension of acne biology

Inflammation is present throughout acne development, including the invisible microcomedone stage. Blemish care therefore should not begin only after lesions become visible.

Published literature reports that salicylic acid modulates multiple inflammation-related pathways, including arachidonic-acid metabolism and inflammatory signaling. Together with its desmolytic and comedolytic actions, this supports both purification and stabilization.

Sebum production + abnormal keratinization

↓

Changed follicular microenvironment

↓

Microbial involvement

↓

Amplified inflammatory cascade

↓

Erythema, papules and post-acne marks

Salicylic acid intervenes at several upstream points: keratinization, the follicular environment and inflammation.

These mechanism-level statements reflect literature consensus and explain ingredient-level biological relevance. They do not constitute pharmaceutical treatment claims.

Mechanism review: Arif T. Clin Cosmet Investig Dermatol. 2015;8:455–461.

CLINICAL EVIDENCE 01 · ASIAN ACNE STUDY

30% salicylic acid peel: a 12-week study in Asian patients with acne

35

Asian participants

Mild to moderate

Facial acne

30%

Salicylic acid peel

Every 2 weeks

One treatment

12 weeks

Observation period

77.1%

Reported moderate or good improvement

• Significant reduction in inflammatory lesions
• Significant reduction in non-inflammatory lesions
• Significant decrease in overall acne severity
• No statistically significant worsening in stratum-corneum hydration, surface lipids, skin pH or TEWL

Lee HS, Kim IH. Salicylic acid peels for the treatment of acne vulgaris in Asian patients. Dermatol Surg. 2003;29:1196–1199.

This is published clinical evidence for salicylic acid, not a finished-product efficacy trial of NanoActive™ SA.

CLINICAL EVIDENCE 02 · COMEDONE COUNT

Mean facial comedone count fell by approximately 75% over 10 weeks

Statistical significance

p = 0.001

Study information

Participants: 16 Japanese patientsSystem: 30% salicylic acid in PEGFrequency: once every 2 weeksDuration: 10 weeks

Mean count decreased from 39.3 at baseline to 9.2 at Week 10, with continued improvement throughout follow-up.

Hashimoto Y, et al. Salicylic acid peels in polyethylene glycol vehicle for the treatment of comedogenic acne in Japanese patients. Dermatol Surg. 2008;34:276–279.

Published evidence for a 30% salicylic acid–PEG peel, not a finished-product efficacy trial of NanoActive™ SA.

POST-ACNE MARKS · UNEVEN TONE

From acne to post-acne marks: a framework for managing pigmentation

How salicylic acid can improve uneven tone

① Normalize exfoliation: accelerate surface renewal

↓

② Remove pigment-containing corneocytes: lift superficial deposited pigment

↓

③ Improve acne-related inflammation: reduce conditions that promote new marks

↓

A more even-looking skin tone

Salicylic acid is not a tyrosinase inhibitor. Its tone-related value comes from the combined effects of keratin renewal and inflammation management, not direct inhibition of melanin synthesis.

Comparative clinical evidence

30% salicylic acid vs 30% glycolic acidMild-to-moderate acne with post-inflammatory hyperpigmentation (PIH)

Study findings

Both peel regimens improved PIH; the salicylic acid group showed better tolerability in this study; relevant to combined acne and post-acne-mark concerns.

The literature also documents salicylic acid use in superficial peels for melasma and photo-induced uneven tone.

Reference: Arif T. Clin Cosmet Investig Dermatol. 2015;8:455–461.

TEXTURE & PHOTOAGING

Beyond blemish care: keratin renewal and younger-looking texture

Controlled keratin renewal can address not only blemishes, but also surface features associated with aging and photodamage:

• Roughness and grainy texture
• Dullness and loss of radiance
• Fine surface lines
• Uneven texture
• Visible signs of photoaging

Change from baseline with a sodium salicylate formulation

Evidence boundary: The study tested a sodium salicylate formulation, not free salicylic acid. Histology also indicated increases in fibrillin and procollagen I. The findings support salicylate/exfoliation biology and are not direct clinical evidence for NanoActive™ SA.

Merinville E, et al. Three clinical studies showing the anti-aging benefits of sodium salicylate in human skin. J Cosmet Dermatol. 2010;9:174–184. Wrinkle depth and skin roughness decreased significantly at Weeks 4 and 8.

THE FORMULATION PARADOX

The challenge with salicylic acid is delivery, not efficacy

Salicylic acid has limited solubility in water at room temperature. Traditional clear aqueous products often rely on ethanol, glycols, surfactant solubilization, partial neutralization and precise pH management, creating a persistent trade-off between efficacy and formulation elegance.

Traditional free-salicylic-acid formulation pathway

Salicylic acid powder

↓

Solvent system

↓

Partial neutralization

↓

pH adjustment

↓

Trade-offs in crystallization, irritation and sensory profile

Each step solves one problem while introducing another compromise.

NanoActive™ SA technology pathway

NanoActive™ SA

↓

Pre-engineered nano-delivery

↓

Easy incorporation into the aqueous phase

↓

Controlled active delivery · formulation freedom

The carrier addresses solubility so formulators regain design flexibility. Delivery technology is the dividing line in modernizing salicylic acid.

FREE ACID & pH

The free-acid state determines effective delivery

Salicylic Acid ⇌ Salicylate− + H+

Molecular form (free acid)　　Ionic form (salicylate)

pH < pKa

Free acid predominates, with a greater tendency to penetrate.

pKa ≈ 3.0

Key reference point for the ionization equilibrium.

pH > pKa

The salt form predominates, increasing water solubility.

01 Molecular and ionic forms

They differ in solubility, partition coefficient and skin penetration.

02 pH determines equilibrium

Small pH adjustments can change the free-acid fraction in the same formulation.

03 Carrier and pH jointly affect penetration

The formulation itself is part of salicylic acid performance.

04 Cost of conventional neutralization

Higher water solubility comes with a changed effective free-acid fraction.

PURISOME® Technology proposition: A nanocarrier environment supports effective salicylic acid delivery while improving formulation compatibility and reducing reliance on high solvent levels and complex neutralization strategies.

THE PURIPHARM RESPONSE

NanoActive™ SA: PuriPharm’s technology response

NanoActive™ SANano-encapsulated salicylic acidINCI: Salicylic AcidPowered by PURISOME® FlexVes™ Liposome Technology

Maintains an effective free-acid state

The carrier environment protects the effective form of salicylic acid.

Aqueous formulation compatibility

Disperses stably and incorporates easily into aqueous systems.

Potential for clear formulations

Supports modern formats such as clear serums and gels.

Reduced solvent dependence

Reduces the need for large amounts of ethanol or polyols.

Controlled delivery

Gradual release produces more even exposure.

Improved skin comfort

A sustained-release approach supports a better user experience.

Potential for follicular targeting

Follicular reservoir effect and localized enrichment.

Face and scalp applications

One platform supports multiple use cases.

This is a redesigned delivery pathway for salicylic acid, not merely salicylic acid placed inside a carrier.

THE TECHNOLOGY PLATFORM

PURISOME® FlexVes™ Liposome Technology

PuriPharm’s proprietary advanced nanoliposomal platform uses skin-compatible phospholipid bilayer vesicles.

Cross-sectional schematic: amphiphilic phospholipids self-assemble into a bilayer that encapsulates or associates with the active.

01 Improved formulation compatibility

A water-dispersed format bypasses the solubility bottleneck.

02 Controlled, sustained release

Carrier association releases the active gradually through interfacial processes.

03 Lower potential for localized irritation

Avoids sudden skin contact with a high concentration of free acid.

04 Improved deposition and delivery

Skin-compatible lipids promote active deposition in the target region.

Hereafter referred to as PURISOME® Technology. Its four delivery advantages support the same goal: bringing the active to the intended site at an appropriate rate.

DELIVERY MECHANISM

PURISOME® FlexVes™: a redesigned salicylic acid delivery pathway

Schematic: larger particles remain on the surface because they cannot pass through intercellular gaps, while smaller nanocarriers can move along these gaps and release the active.

01 Interaction with stratum-corneum lipids

Skin-compatible phospholipids approach intercellular lipids.

02 Gradual release

The active is progressively released from the carrier interface.

03 Follicular deposition

The carrier moves along the follicular pathway and enriches the target region.

Nanoscale delivery · skin-compatible lipids · controlled release · improved compatibility · follicular-delivery potential · better sensory profile

The schematic follows standard pharmaceutics models of phospholipid bilayer vesicle interactions with skin.

FOLLICULAR TARGETING

Follicular targeting and the follicular-reservoir concept

Nanoparticles vs free drug: a, stratum-corneum surface; b, enrichment in the follicular infundibulum; c, migration deeper along the follicle.

Particles deposit in the follicular infundibulum and diffuse into surrounding tissue.

Follicular targeting · follicular reservoir · localized enrichment

• Blackheads and comedones
• Oily pores
• Scalp buildup
• Keratin buildup within follicles

Statements about follicular targeting and reservoirs are based on the PURISOME® Technology platform’s delivery concept and are consistent with existing NanoActive™ platform data.

Left image adapted from Prow TW, et al. Nanoparticles and microparticles for skin drug delivery. Adv Drug Deliv Rev. 2011;63:470–491.

CONTROLLED RELEASE & SKIN COMFORT

From concentration peaks to gradual release

Traditional free salicylic acid

Rapid local exposure produces a concentration peak, with potential stinging and irritation.

NanoActive™ SA

Carrier-associated delivery supports gradual release, more even local exposure and potential for improved comfort.

Nanocarrier occlusion effectSmaller particles and a higher number of carriers per unit area can form a denser lipid film on the skin surface. This may improve stratum-corneum hydration, promote active penetration and reduce water loss, adding another mechanistic basis for efficacy with comfort.

FOR FORMULATORS

Making salicylic acid easier to formulate and use

1. Easy incorporation and process-friendly handling
2. Suitable for aqueous systems
3. Potential for transparent and clear formulations
4. Reduced dependence on high ethanol levels
5. Less need for aggressive solubilization strategies
6. Compatible with serums, gels, cleansers and scalp formats
7. Can be added at low temperature, depending on the process

Process and compatibility guidance	Details
Suggested use level	Approximately 1–5%
Addition method	Add at low temperature
Compatibility note	Avoid combining with divalent or trivalent metal ions

Based on historical PuriPharm technical materials. If this information differs from the latest product TDS, follow the current TDS.

Formulation freedom is itself a product advantage.

APPLICATION MAP

One application map, from face to scalp

FACE

Anti-acne serumPore-refining serumKeratin-regulating tonerCleanserClear gelMoisturizer for oily skinBlemish care

BODY

Body acne sprays and lotionsKeratosis pilaris careExfoliating body washCare for rough areas

SCALP & HAIR

Anti-dandruff shampooShampoo for oily scalpScalp serumScalp exfoliating treatmentScalp-cleansing products

One technology platform supports three major application areas: face, body and scalp.

SCALP & HAIR 01 · SCALP BIOLOGY

From facial pores to scalp follicles

Persistent scalp concerns

01 Scalp keratin buildup02 Excess scalp oil03 Adherent flakes04 Buildup at follicular openings05 Scalp cleanliness and freshness06 Disrupted scalp-renewal rhythm

Why salicylic acid suits scalp care

Desmolytic action: softens and removes corneocytes adhering to the scalp surface.Reduced surface buildup: addresses adherent layers formed by oil and keratin.Clearer follicular openings: lipophilicity supports entry along the sebum-rich environment.Improved appearance of oily scalp: a fresher scalp and lighter-feeling roots.

Scalp follicles present a problem structurally analogous to facial pores. Scalp care is another application of the same keratin biology, not merely an extension of facial care.

SCALP & HAIR 02 · DANDRUFF CARE

Scalp purification and dandruff care

Biology of dandruff

Dandruff is associated with abnormal desquamation of the stratum corneum.Malassezia plays an important role in dandruff biology.Effective management should address flake control, microbial factors and overall scalp condition.

Scalp positioning of NanoActive™ SA

① Desmolytic scalp active② Scalp-flake removal③ Oily-scalp care④ Follicular cleansing⑤ Supporting ingredient in anti-dandruff shampoo systems

Scientific boundary: salicylic acid should not be claimed as a standalone antifungal ingredient. In multi-ingredient anti-dandruff systems, it contributes keratin management and flake control.

Suggested formats: anti-dandruff shampoo · shampoo for oily scalp · scalp serum · scalp treatment liquid · scalp exfoliating treatment · pre-shampoo scalp care

Dandruff systems require multiple complementary mechanisms. NanoActive™ SA addresses the keratin and flake-control component.

COMPARISON

Traditional salicylic acid vs NanoActive™ SA

Dimension	Traditional salicylic acid	NanoActive™ SA
Aqueous formulation difficulty	High: limited water solubility	Low: easy dispersion and incorporation in water
Crystallization risk	Potential precipitation and crystallization	Carrier encapsulation lowers risk
Solvent dependence	Often requires high levels of ethanol or polyols	Dependence substantially reduced
pH management	Precise control changes the free-acid fraction	A more flexible formulation window
Delivery profile	Rapid release and local concentration peak	Gradual release and more even exposure
Skin comfort	Stinging possible at high concentration	Sustained-release approach with comfort potential
Clear-formulation capability	Limited	Supports clear, transparent formulations
Follicular delivery	Relies on compensating formulation engineering	Potential for follicular targeting and reservoir deposition
Dosage-form flexibility	Limited selection	Serums, gels, cleansers and scalp formats
Fit for scalp applications	Dual challenge of solubilization and irritation	Aqueous-friendly and suited to modern scalp formats

VALUE PROPOSITION

NanoActive™ SA: a four-dimensional value proposition

EFFICACY｜Classic salicylic acid, multidimensional purification

Peer-reviewed literature supports the combined mechanisms of keratin renewal, comedolysis and inflammation modulation.

DELIVERY｜PURISOME® nanoliposomal delivery

Skin-compatible phospholipid bilayer vesicles carry the active and support follicular targeting and reservoir deposition.

COMFORT｜Sustained-release concept for a better experience

Gradual release smooths concentration peaks and troughs, adding comfort potential to efficacy.

FORMULATION｜Aqueous-friendly with greater design freedom

From serums to shampoos, the platform enables salicylic acid formats that were previously difficult to formulate.

Evidence for efficacy, technology for delivery, attention to experience and room for formulation.

REFERENCES

References and evidence grading

Published literature cited in this presentation

1. Lee HS, Kim IH. Salicylic acid peels for the treatment of acne vulgaris in Asian patients. Dermatol Surg. 2003;29:1196–1199.
2. Hashimoto Y, et al. Salicylic acid peels in polyethylene glycol vehicle for the treatment of comedogenic acne in Japanese patients. Dermatol Surg. 2008;34:276–279.
3. Arif T. Salicylic acid as a peeling agent: a comprehensive review. Clin Cosmet Investig Dermatol. 2015;8:455–461.
4. Merinville E, et al. Three clinical studies showing the anti-aging benefits of sodium salicylate in human skin. J Cosmet Dermatol. 2010;9:174–184.

Clinical evidence for salicylic acid

References [1] and [2]: 30% peel systems, not finished-product studies.

Evidence for a salicylate derivative

Reference [4]: sodium salicylate, supporting the biological pathway.

Mechanism and review literature

Reference [3]: exfoliation, comedolysis and skin-tone applications.

None of the published references cited here constitutes a finished-product efficacy trial of NanoActive™ SA.

NANOACTIVE™ SA

Making classic salicylic acid more suitable for next-generation formulations

Powered by PURISOME® FlexVes™ Liposome Technology

PuriPharm Co. Ltd.

ENGLISH VERSIONComplete English Article

PURIPHARM CO., LTD. · TECHNICAL PRESENTATION · COSMETIC ACTIVE INGREDIENT

NANOACTIVE™ SERIES · NANO-ENCAPSULATED ACTIVES

NanoActive™Azelaic Acid 50%

Nano-encapsulated Azelaic Acid 50%

Multi-pathway skin clarification · Pigment management · Follicular clarification

Abstract: 50% high-payload azelaic acid combined with next-generation nanoliposome delivery. Four published evidence pathways—keratinization regulation, microbiome clarification, inflammation modulation, and pigment management—address the classic formulation paradox of an effective but difficult-to-formulate molecule.

Powered by PURISOME® FlexVes™ Liposome TechnologyPuriPharm Co., Ltd.

PART II · ENGLISH VERSION

POSITIONING · PRODUCT POSITIONING

Re-engineering how azelaic acid is delivered

50% high-payload azelaic acid × next-generation nano delivery

Powerful multi-pathway biology

↓

A difficult-to-formulate molecule

↓

PURISOME® nanoliposome delivery

↓

Modern azelaic acid formulation

Azelaic acid has long-established value in blemish-prone skin, pigmentation, and follicular biology. Its main limitation is formulation and delivery rather than efficacy. NanoActive™ Azelaic Acid 50% addresses this classic paradox through a 50% active payload and PURISOME® nanoliposome delivery.

ONE MOLECULE · MULTIPLE PATHWAYS

The multidimensional biology of azelaic acid

Azelaic acid is more than an anti-acne ingredient. It is one of the few multifunctional actives that simultaneously addresses keratinization, the microbiome, inflammation, and pigmentation pathways.

01

Keratinization regulation

Regulates terminal differentiation of keratinocytes in the follicular infundibulum and helps reduce follicular keratin buildup at its source.

02

Microbiome clarification + inflammation modulation

Interferes with intracellular bacterial protein synthesis, reduces neutrophil ROS release, and modulates inflammatory signaling.

03

Pigment management

Competitively inhibits tyrosinase to support the management of post-acne marks, visible hyperpigmentation, and uneven tone.

04

Follicular and scalp microenvironment

Published evidence of follicular accumulation extends its potential use to scalp and follicular care.

Blemish-prone skin · Abnormal keratinization · Microbiome · Visible inflammation · Post-acne marks · Uneven tone · Oxidative stress · Follicular and scalp care: multiple pathways addressed by one molecule.

THE FORMULATION PARADOX

Effective, yet difficult to formulate

≈ 0.24%

Intrinsic water solubility of azelaic acid at 20°C · reported in the literature

15–20%

Use levels in established topical efficacy research · historical literature and pharmaceutical products

How can a high-dose, poorly soluble molecule be incorporated into an elegant modern formulation?

Note: 15–20% refers to use levels in historical literature and pharmaceutical products. It illustrates the formulation challenge and does not represent a recommended cosmetic use level for NanoActive™ Azelaic Acid 50%.

MECHANISM I · KERATINIZATION REGULATION

Keratinization regulation: reducing follicular keratin buildup at the source

Abnormal keratinocyte differentiation

↓

Follicular hyperkeratinization

↓

Microcomedone formation

↓

Comedones and clogged pores

↓

Inflammatory lesions

Published evidence shows that azelaic acid has antikeratinizing activity and helps restore disrupted terminal differentiation of keratinocytes in the follicular infundibulum.

• Reduces follicular hyperkeratosis
• Decreases the number and volume of keratohyalin granules
• Improves abnormal follicular keratinization and restores terminal keratinocyte differentiation

Cosmetic value positioning: helps reduce follicular keratin buildup at its source.

Pathological sequence in acne-prone follicles: abnormal keratinization is the starting point. Normal Follicle vs Hyperkeratinized Follicle.

PUBLISHED EVIDENCE · HISTOLOGIC EVIDENCE OF KERATINIZATION NORMALIZATION

Marked reduction and normalization of hyperkeratosis after 8–12 weeks

8–12 weeks

20% azelaic acid cream, applied twice dailyMarked reduction or normalization of intrafollicular and interfollicular hyperkeratosis

01

Marked reduction in hyperkeratosis

Histologic observations showed marked improvement or normalization of both intrafollicular and interfollicular hyperkeratosis.

02

Fewer and smaller keratohyalin granules

The number and size of keratohyalin granules decreased, indicating normalization of the keratinization process.

03

Normalization of terminal keratinocyte differentiation

Disrupted terminal differentiation was corrected, restoring a healthier follicular keratinization pattern.

Gollnick H. Azelaic acid — pharmacology, toxicology and mechanisms of action on keratinization in vitro and in vivo. J Dermatol Treat. 1993.Published evidence on conventional azelaic acid formulations; not a finished-product clinical trial of NanoActive™ Azelaic Acid 50%.

MECHANISM II · FOLLICULAR MICROBIOME

Follicular microbiome: antimicrobial action from within the cell

Azelaic acid

↓

Transport into the bacterial cell

↓

Interference with intracellular protein synthesis

↓

Reduced microbial growth and proliferation

This is more specific than a general claim of “killing acne bacteria.” Published mechanistic research indicates that azelaic acid enters bacterial cells via transport mechanisms and interferes with intracellular protein synthesis, thereby reducing microbial growth and proliferation.

01

Cutibacterium acnes

Formerly Propionibacterium acnes; the historical name is retained when citing original publications.

02

Staphylococcus epidermidis

A resident skin bacterium examined in microbiome-related research.

PUBLISHED EVIDENCE · ANTIMICROBIAL ACTION

At least 96% reduction in skin-surface and follicular-associated bacteria after 8 weeks

≥96%

Reduction in bacteria sampled from the skin surface and follicles

20%

Azelaic acid cream

8 weeks

Topical treatment period

Surface + follicle

Two sampling levels

After 8 weeks of topical treatment with 20% azelaic acid cream, counts of propionibacteria and staphylococci on the skin surface and within follicles fell by at least 96%, demonstrating microbiome clarification that reaches into the follicle.

Holland KT, Bojar RA. Antimicrobial effects of azelaic acid. J Dermatol Treat. 1993.Published evidence using a conventional 20% azelaic acid cream; not a finished-product clinical trial of NanoActive™ Azelaic Acid 50%.

MECHANISM III · ROS & INFLAMMATION

Reducing oxidative stress and modulating inflammatory signals

Azelaic acid

↓

Reduced neutrophil ROS release

↓

Lower oxidative inflammatory burden

Pathway examined in published research: CD36 → NADPH oxidase → ROS → MAPK → NF-κB

The literature reports that azelaic acid can reduce reactive oxygen species generation and downregulate oxidative inflammatory cascades. Related studies also involve innate immune signaling nodes such as TLR2, KLK5, and LL-37/cathelicidin, although the strength of evidence varies by target.

01

Soothes blemish-prone skin

Cosmetic value

02

Supports improvement in the appearance of redness

Cosmetic value

03

Improves the inflammatory environment around clogged follicles

Cosmetic value

04

Supports a healthier-looking skin texture

Cosmetic value

CLINICAL EVIDENCE · INFLAMMATORY LESIONS

Greater reduction in inflammatory lesion counts with 15% azelaic acid gel

• 251 adult patients
• Moderate-to-severe papulopustular rosacea
• 15-week controlled clinical study
• 15% azelaic acid gel vs active comparator gel; the azelaic acid group had a greater mean reduction in inflammatory lesion count

This evidence supports the anti-inflammatory skin biology of azelaic acid. The comparator is described generically and no commercial brand is identified.

Elewski BE, et al. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea. Arch Dermatol. 2003;139:1444–1450.

MECHANISM IV · PIGMENT CONTROL

Pigment management through competitive tyrosinase inhibition

L-Tyrosine

↓

Tyrosinasecompetitively inhibited by azelaic acid

↓

L-DOPA

↓

Dopaquinone

↓

Melanin

Azelaic acid has been reported to competitively inhibit tyrosinase and to have specific biological relevance in hyperactive melanocyte systems. Together with reduced ROS, modulation of melanogenesis, and improvement of the post-inflammatory environment, this forms a more complete pigment-management pathway. Azelaic acid is not a bleaching agent; it is a multi-pathway pigment-management active.

• Post-acne marks
• Uneven tone
• Visible hyperpigmentation
• Management of dullness and skin clarity

CLINICAL EVIDENCE · HYPERPIGMENTATION

20% azelaic acid: an established clinical foundation for pigment management

• Randomized, double-blind, controlled clinical study
• 329 female participants
• 24 weeks · 20% azelaic acid vs 4% hydroquinone
• Median reduction in lesion area: approximately 71% vs approximately 78%
• Good/excellent overall improvement: 64.8% vs 72.5%
• No statistically significant difference between groups in overall improvement

Clinical research in melasma and other hyperpigmentation concerns shows that azelaic acid has an efficacy foundation comparable with that of a classic reference ingredient.

Gupta AK, et al. The treatment of melasma: A review of clinical trials. J Am Acad Dermatol. 2006;55:1048–1065.

POST-ACNE MARKS · FROM BLEMISH TO MARK

Pigmentation may persist after the blemish resolves

Follicular blockage

↓

Inflammation

↓

ROS / inflammatory mediators

↓

Melanocyte activation

↓

Post-inflammatory hyperpigmentationPIH / post-acne marks

Five stages addressed by azelaic acid: keratinization, the inflammatory environment, microbiome balance, tyrosinase, and oxidative stress.

From blemish to mark: one active addresses a more complete biological pathway.

FOLLICULAR DELIVERY MATTERS · EVIDENCE OF FOLLICULAR ACCUMULATION

The follicle is where azelaic acid needs to reach

• Single topical application of 20% azelaic acid cream
• 9 healthy adults · forehead and back
• Follicular casts collected over 5 hours
• Measurable accumulation of azelaic acid in the pilosebaceous unit

36–251

mmol/L · estimated peak concentration in back follicles

2–112

mmol/L · estimated peak concentration in forehead follicles

Follicular concentrations reached or exceeded the concentrations required to inhibit C. acnes and S. epidermidis in vitro. This provides a scientific foundation for the PURISOME® follicular-delivery concept.

Bojar RA, et al. Follicular concentrations of azelaic acid after a single topical application. Br J Dermatol. 1993;129:399–402.Published data on a conventional azelaic acid formulation; not a NanoActive™ Azelaic Acid 50% product study.

WHY NANO DELIVERY MATTERS

Azelaic acid needs better delivery, not proof of efficacy

Formulation realities of conventional azelaic acid	NanoActive™ delivery rationale
Extremely low intrinsic water solubility (≈0.24% at 20°C)	NanoActive™ Azelaic Acid 50%
Historical products rely on high effective use levels	PURISOME® liposomal delivery · high active payload
Risk of crystallization, recrystallization, and particles	Improved formulation compatibility · lower free-crystal burden
Risk of a gritty skin feel and high solids loading	Controlled skin and follicular delivery
Difficult to incorporate into low-viscosity, transparent modern dosage forms
Limited suitability for serums and scalp formats

Delivery efficiency, not simply the concentration added.

SCIENTIFIC PRECEDENT · PHOSPHOLIPID VESICLE DELIVERY

Vesicular delivery of azelaic acid: scientific exploration since 2004

As early as 2004, azelaic acid was systematically investigated in phospholipid-based vesicular systems, including liposomes and ethosomes. Vesicle morphology, particle-size distribution, and in vitro release were fully characterized.

• Characterization of phospholipid vesicle morphology and size distribution
• Franz-cell in vitro release curves
• Systematic comparison of release from liposomes and ethosomes

Phospholipid-vesicle delivery is an established scientific strategy for improving topical azelaic acid formulation and release behavior.

Esposito E, et al. Ethosomes and liposomes as topical vehicles for azelaic acid: A preformulation study. J Cosmet Sci. 2004;55:253–264.

PUBLISHED PROOF OF CONCEPT · LIPOSOMAL AZELAIC ACID

10% liposomal azelaic acid produced greater stratum corneum deposition than a conventional 20% formulation

• Approximate liposome diameter: 211 nm
• PDI ≈ 0.22–0.24, indicating a uniform distribution
• With half the active concentration, stratum corneum deposition increased 2.3–3.6-fold

Delivery efficiency, not simply the concentration added.

Burchacka E, et al. Biomed Pharmacother. 2016;83:771–775. DOI: 10.1016/j.biopha.2016.07.014An independently published proof-of-concept study of liposomal azelaic acid; not PURISOME® technology data.

DELIVERY TECHNOLOGY

PURISOME® FlexVes™

A delivery system redesigned for high-payload azelaic acid

PURISOME® is PuriPharm’s proprietary nanoliposome delivery platform. Nanoscale phospholipid-bilayer vesicles carry a 50% azelaic acid payload from an aqueous environment, through the stratum corneum and follicular openings, to support local accumulation and controlled release.

01

Improved formulation compatibility

FORMULATION

02

Optimized skin and follicular delivery

DELIVERY

03

Sustained release

CONTROL

04

Improved user experience with a high active load

COMFORT

Powered by PURISOME® FlexVes™ Liposome Technology

PRODUCT PROFILE

NanoActive™ Azelaic Acid 50%

Nano-encapsulated Azelaic Acid 50% · Powered by PURISOME® FlexVes™ Liposome Technology

Product name	NanoActive™ Azelaic Acid 50%
INCI	Azelaic Acid
Active content	50% azelaic acid (raw-material active-payload specification)
Delivery technology	PURISOME® FlexVes™ Liposome Technology
Active molecule	Azelaic acid
Chemical class	Saturated C9 dicarboxylic acid
Molecular formula	C9H16O4
Molecular weight	188.22
Structural formula	HOOC–(CH2)7–COOH

Azelaic acid is a naturally occurring saturated nine-carbon dicarboxylic acid. The 50% figure is the raw material’s active-content specification, not the use concentration in a finished product. Particle size, pH, recommended use level, and other technical parameters should follow the latest PuriPharm TDS.

HIGH ACTIVE PAYLOAD

50% azelaic acid active payload

50%

AZELAIC ACID PAYLOAD

50% high active payload

↓

PURISOME® nano delivery

↓

Greater formulation freedom

50% is the active-content specification of the raw material, not the use concentration in a finished formulation.

A high-payload raw material allows formulators to deliver a meaningful azelaic acid level without introducing excessive carrier material into the finished product. This preserves valuable formulation space for refining skin feel, stability, and dosage form, leaving genuine freedom for serums, gels, emulsions, and scalp formats.

DELIVERY MECHANISM

Controlled release from the aqueous phase into the follicle

Aqueous environment

↓

Nanolipid vesicles

↓

Stratum corneum

↓

Follicular opening

↓

Local controlled release

Nanoscale phospholipid vesicles carry azelaic acid along the skin surface and follicular pathways, supporting local accumulation and sustained release in the target area. In this way, the delivery destination becomes part of formulation design.

BLEMISH-PRONE SKIN · MULTI-PATHWAY CARE

Azelaic acid addresses three of the four acne pathways

Pathway	Role	Description
Follicular hyperkeratinization	Core action	Regulates keratinization and addresses the source of follicular blockage
Microbial colonization	Core action	Interferes with intracellular bacterial protein synthesis and clarifies the follicular microbiome
Inflammation / ROS	Core action	Reduces oxidative stress and modulates inflammatory signaling
Sebum–follicle environment	Associated environment	Indirectly relates to this pathway by improving the follicular microenvironment

Scientific rigor note: current literature does not support a claim that azelaic acid directly suppresses sebum secretion, so no such claim is made here. Its value lies in acting simultaneously on three core pathways: keratinization, the microbiome, and inflammatory oxidative stress.

Multi-pathway management for blemish-prone skin: a complete path from keratinization and the microbiome to inflammation and pigmentation.

COMBINATION INSPIRATION · COMBINATION RESEARCH

Azelaic acid × salicylic acid: clinical exploration of a multi-pathway combination

Study design · randomized controlled trial	Published results
34 patients with acne · split-face design	Inflammatory and non-inflammatory acne lesions improved significantly on both sides
4 treatments · 2-week intervals	The SA + AA side produced higher patient satisfaction and less discomfort
20% salicylic acid + 20% azelaic acid
Comparator side: 25% trichloroacetic acid (TCA) chemical peel

Azelaic acid can be combined with other keratinization-regulating actives to build multi-pathway solutions for blemish-prone skin.

This was a clinical chemical-peel protocol. It is presented as scientific inspiration for combination concepts and does not constitute a cosmetic formulation recommendation or concentration guideline.

Abdel Hay R, et al. Clinical and dermoscopic evaluation of combined salicylic acid 20% and azelaic acid 20% versus trichloroacetic acid 25% chemical peel in acne: an RCT. J Dermatolog Treat. 2019;30(6):572–577. DOI: 10.1080/09546634.2018.1484876

SCALP CARE

From skin follicles to scalp follicles

The same follicular biology also applies to the scalp. Scalp care involves more than oil control.

Six microenvironmental concerns in scalp follicles: keratin buildup, follicular blockage, the inflammatory environment, microbiome balance, oxidative stress, and the sebum environment.

• Care for oily scalp · clarifying scalp formulas
• Follicular cleansing · acne-prone scalp
• Scalp microbiome management
• Scalp soothing and renewal

HAIR-FOLLICLE BIOLOGY

5α-reductase: an exploratory mechanism for scalp applications

Testosterone

↓

5α-Reductasepresent in human hair follicles

↓

DHT

Published biochemical research examined the inhibitory effect of azelaic acid—particularly when combined with zinc—on 5α-reductase activity in human skin. This provides mechanistic scientific support for exploring scalp applications.

Scientifically rigorous product-development language:

• Supports management of the follicular microenvironment
• Research on 5α-reductase-related mechanisms provides a new scientific direction for scalp applications
• Provides a mechanistic product-development rationale for oily-scalp and androgen-related follicular care

Stamatiadis D, et al. Inhibition of 5α-reductase activity in human skin by zinc and azelaic acid. Br J Dermatol. 1988;119:627–632.

APPLICATION MAP

One active for the face, body, and scalp

01

FACE

Anti-blemish oil-control serumPore-care serumPost-acne mark repair serumBrightening serumUneven-tone careRedness-care formulaMoisturizer for oily skinClarifying cleanser

02

BODY

Back-acne careChest-acne careBody hyperpigmentation serumFollicular roughness care

03

SCALP

Clarifying scalp serumOily-scalp serumFollicular-care serumScalp keratinization careSoothing scalp productsClarifying shampooHair-root serum

All application directions are positioned for cosmetic use. Compatibility with specific dosage forms should follow the latest PuriPharm TDS and formulation support.

COMPARISON · FORMULATION VALUE

Conventional azelaic acid powder vs NanoActive™ Azelaic Acid 50%

Dimension	Conventional azelaic acid powder	NanoActive™ Azelaic Acid 50%
Aqueous-phase compatibility	Extremely low intrinsic water solubility (≈0.24% at 20°C)	Pre-engineered nanodispersion system
Dispersion difficulty	Requires solubilization or suspension strategies	Uniform dispersion and easy incorporation
Solids loading	High use levels create a high solids load	50% high payload reduces formulation burden
Crystallization management	Free crystalline active; recrystallization must be controlled	Carrier-associated active delivery
Skin feel	Risk of grittiness	Smooth sensory profile designed for modern formats
Delivery strategy	Primarily passive diffusion	PURISOME® nanoliposome delivery
Follicular delivery	Limited potential	Delivery designed for the follicular pathway
Release behavior	Sustained release is difficult to achieve	Carrier-mediated sustained release
Formulation flexibility	Mainly high-viscosity suspension formats	Serums / gels / emulsions / scalp formats
Scalp suitability	Difficult	Good

KEY VALUE PROPOSITION

Making high-concentration azelaic acid more suitable for next-generation formulations

01

Multi-pathway azelaic acid biology

MULTI-ACTION

02

50% high payload

HIGH PAYLOAD

03

PURISOME® nano delivery

PRECISION DELIVERY

04

Greater freedom for modern formulations

FORMULATION FREEDOM

05

From facial blemish-prone skin to scalp-follicle care

SKIN + SCALP

NanoActive™ Azelaic Acid 50%

Powered by PURISOME® FlexVes™ Liposome TechnologyPuriPharm Co., Ltd. · www.puriactives.com · service@puripharm.com

NanoActive™ Azelaic Acid 50%Powered by PURISOME® FlexVes™ Liposome TechnologyPuriPharm Co., Ltd. · www.puriactives.com · service@puripharm.com

PURIPHARM CO. LTD. · INGREDIENT SCIENCE PLATFORM

NanoActive™ BatyCer™

Biomimetic Skin Barrier Lipid Platform

Powered by PURISOME® Liposome Delivery Technology

INCI NAME — BATYL ALCOHOL

02 · BARRIER SCIENCE

The New Era of Skin Barrier Science

Technology generation	Core direction
Traditional moisturization	Surface hydration
Occlusive barrier technology	Reduction of surface water loss
Ceramide-based lipid repair	Replenishment of essential barrier lipids
Biomimetic lipid reconstruction	Restoration of skin-like lipid organization
Nano-delivery lipid platform	Nanoscale delivery of ordered biomimetic lipid systems

Each generation of barrier care has moved closer to the skin’s own biology — from surface hydration toward the restoration of its native lipid organization.

NanoActive™ BatyCer™ embodies this progression: physiological lipids, engineered into an ordered architecture, delivered at the nanoscale.

“The future of barrier care is not only hydration — it is lipid architecture restoration.”

03 · PRODUCT OVERVIEW

NanoActive™ BatyCer™

Advanced Skin Barrier Lipid Platform

A multifunctional lipid delivery system that reassembles the skin’s native barrier lipids into a single, biomimetic stratum corneum architecture.

INTEGRATED LIPID SYSTEM

01	Batyl Alcohol — signature functional lipid
02	Ceramide NP — essential barrier lipid
03	Cholesterol — membrane stabilizer
04	Phospholipids — vesicle-forming carriers
05	Stearic Acid — physiological fatty acid

04 · THE SIGNATURE LIPID

Batyl Alcohol — The Signature Functional Lipid

INCI NAME

Batyl Alcohol

CHEMICAL IDENTITY

Glyceryl Octadecyl Ether (1-O-octadecyl glycerol)

STRUCTURAL CHARACTERISTICS

01	C18 alkyl chain — long-chain lipid affinity
02	Glycerol ether backbone — high chemical stability
03	Amphiphilic lipid structure — membrane compatibility

“Batyl Alcohol bridges conventional emollient technology and biomimetic lipid engineering.”

05 · SCIENTIFIC RATIONALE

Why Batyl Alcohol?

Scientific feature	Significance
01 Lipid membrane compatibility	An amphiphilic alkylglycerol that partitions readily into lipid membranes and integrates with bilayer structures.
02 Interaction with stratum corneum lipid domains	Its C18 chain aligns with the intercellular lipid matrix, engaging the skin’s native barrier domains.
03 Support of ordered lipid organization	Promotes the formation of ordered lamellar phases — the structural basis of a competent barrier.
04 Compatibility with lipid delivery systems	Readily incorporated into phospholipid vesicles, enabling stable, nano-enabled delivery formats.

REFERENCE SCIENTIFIC FINDINGS

Alkylglycerol derivatives have demonstrated effects on:

01	— TEWL reduction
02	— Stratum corneum lipid organization
03	— Barrier modulation

Bernal-Chávez SA et al. Alkylglycerol Derivatives, a New Class of Skin Penetration Modulators. Molecules. 2017;22(1):185.

06 · SKIN PHYSIOLOGY

Skin Barrier Lipid Architecture

Structure	Description
Corneocytes	Flattened, protein-rich cells forming the structural “bricks” of the stratum corneum
Intercellular lipid matrix	Lamellar assemblies of Ceramide NP, cholesterol and free fatty acids — the true barrier to water loss
Lamellar organization	Ordered lipid layering governs water retention, barrier integrity, resilience and environmental protection

“The stratum corneum functions as a highly organized lipid membrane system.”

07 · THE ESSENTIAL BARRIER LIPID

Ceramide NP

The Essential Barrier Lipid

Ceramides constitute roughly half of the stratum corneum lipid mass. Among them, Ceramide NP is a dominant species in healthy human skin — and one of the first to decline when the barrier is compromised.

Core function	Physiological significance
Water retention	Forms the hydrophobic lamellar phases that limit transepidermal water loss.
Lamellar organization	Drives the stacking of lipids into long-range ordered lamellar structures.
Barrier cohesion	Cements corneocytes into a cohesive, mechanically resilient barrier.

“Restoring ceramide organization is a fundamental strategy for improving barrier performance.”

08 · PHYSIOLOGICAL LIPID BALANCE

Ceramide NP + Cholesterol + Fatty Acid Synergy

Balanced physiological lipid mixtures accelerate barrier recovery — Ceramide NP enriched systems restore barrier recovery, SC hydration and lipid organization.

09 · THE INNOVATION

Batyl Alcohol Reinforced Lipid Matrix

01	Batyl Alcohol: The structural lipid enhancer enters the platform.
02	Improves lipid compatibility: Harmonizes unlike lipid species within one matrix.
03	Supports membrane organization: Reinforces ordered packing across lipid domains.
04	Enhances biomimetic lipid assembly: A reinforced matrix, closer to the skin’s own architecture.

“Batyl Alcohol functions as a structural lipid enhancer within the barrier lipid platform.”

The result: a lipid matrix with greater coherence, stability and physiological resemblance than ceramide systems alone.

10 · DELIVERY TECHNOLOGY

PURISOME® Nanoliposome Technology

An advanced phospholipid-based nanocarrier that wraps the BatyCer™ lipid complex in a skin-affine bilayer envelope.

01	Lipid protection — shields sensitive lipids from oxidation and degradation
02	Improved dispersion — uniform nanoscale distribution throughout the formula
03	Enhanced formulation flexibility — easy incorporation across emulsion systems
04	Controlled lipid delivery — targeted deposition of barrier lipids at the skin surface

11 · MOLECULAR ARCHITECTURE

Inside the NanoActive™ BatyCer™ Vesicle

Architecture	Function
Outer phospholipid bilayer	Skin-affine vesicle envelope
Cholesterol stabilization	Membrane cohesion and integrity
Batyl Alcohol integration	Structural lipid enhancement
Ceramide NP lipid matrix	Biomimetic barrier core

12 · MECHANISM OF ACTION

From Application to Barrier Performance

01	Application
02	NanoActive™ BatyCer™ deposition
03	Lipid integration
04	Barrier lipid organization
05	Reduced moisture loss
06	Improved skin comfort

Each vesicle carries a complete barrier-lipid repertoire; upon deposition, the lipids merge with the intercellular matrix and re-establish ordered lamellar organization.

13 · BARRIER REINFORCEMENT BENEFITS

Measurable Barrier Performance

01	Supports skin barrier recovery: Ceramide NP enriched lipid systems are documented to restore barrier recovery.
02	Improves hydration retention: Ordered lamellar lipids reduce TEWL and sustain stratum corneum hydration.
03	Enhances skin smoothness: A restored lipid matrix refines surface texture and tactile quality.
04	Strengthens lipid resilience: Alkylglycerol-supported lipid organization reinforces barrier modulation.

14 · HYDRATION SCIENCE

Hydration & Moisture Retention

THE PHYSIOLOGICAL LOGIC

Hydration is governed less by how much water a formula contains than by how well the barrier retains it. By rebuilding ordered lamellar lipids, NanoActive™ BatyCer™ addresses moisture loss at its structural origin.

TEWL — transepidermal water loss, the reference metric for barrier integrity.

15 · SENSITIVE SKIN

Sensitive Skin & Environmental Stress Support

BARRIER DISRUPTION FACTORS	NANOACTIVE™ BATYCER™ SUPPORTS
Cleansing stress — Surfactants strip intercellular lipids	Lipid balance — Replenishes the physiological lipid ratio
Environmental exposure — Pollution and UV challenge barrier lipids	Barrier resilience — Reinforces lipid organization under stress
Dry climate — Low humidity accelerates water loss	Skin comfort — Reduces tightness associated with barrier disruption

Barrier-compromised and sensitive skin states share a common origin: depleted and disorganized stratum corneum lipids. Lipid replenishment is the physiological counter-strategy.

16 · BEYOND SKIN

Advanced Hair Lipid Science

The hair fiber, like the skin barrier, depends on lipid organization. Its protective cuticle is coated in covalently bound surface lipids that chemical and thermal stress progressively remove.

CUTICLE LIPID REPLENISHMENT

NanoActive™ BatyCer™ deposits biomimetic lipids along the fiber surface, helping to re-lubricate lifted cuticle scales and restore a smooth, coherent surface.

17 · HAIRCARE APPLICATIONS

Lipid Science for Haircare Formulas

Application	Positioning
Premium conditioners	Daily lipid replenishment in rinse-off systems
Hair masks	Intensive lipid restoration for damaged fiber
Leave-in treatments	Persistent surface lipid film for daily defense
Scalp barrier products	Extending barrier lipid science to the scalp

CONSUMER-VISIBLE BENEFITS

01	Improved smoothness
02	Enhanced shine
03	Better manageability

Surface lipid replenishment translates directly into sensory properties that consumers can feel and see.

18 · FOR FORMULATORS

Formulation Advantages

Advantage	Description
01 Lipid system compatibility	Integrates smoothly with oils, esters, ceramide systems and phospholipid phases.
02 Easy incorporation into emulsions	Pre-dispersed nanoliposome form — no high-shear solubilization required.
03 Premium skincare concept fit	Biomimetic barrier story aligned with dermo-cosmetic positioning.
04 Multifunctional formulations	One platform spanning facial, body, hair and scalp applications.

“A biomimetic lipid platform that formulates like a modern active — and performs like skin’s own biology.”

19 · APPLICATION OPPORTUNITIES

One Platform, Three Categories

Facial Care	Body Care	Hair Care
Barrier creamsAnti-aging moisturizersSensitive skin products	Dry skin careBody emulsionsIntensive lipid balms	ConditionersHair masksScalp care
Core territory: daily barrier maintenance and recovery for the face	Large-surface barrier support for dry and very dry body skin	Cuticle lipid replenishment from fiber surface to scalp barrier

20 · SCIENTIFIC EVIDENCE LANDSCAPE

Built on Established Science

Evidence stream	Scientific foundation
Batyl Alcohol	Alkylglycerols documented for lipid organization, TEWL reduction and barrier modulation.
Ceramide NP	Physiological ceramide species at the center of barrier restoration research.
Liposomes	Decades of evidence for phospholipid vesicles in advanced topical delivery.

SUPPORTING LITERATURE DOMAINS

01	— Stratum corneum lipid organization and lamellar phase behavior
02	— Ceramide / cholesterol / free fatty acid systems and barrier recovery
03	— Liposomal topical delivery and skin deposition

Three independent evidence streams converge in one ingredient platform.

21 · INNOVATION SUMMARY

A Complete Lipid Engineering Solution

Platform element	Content
Functional Lipid	Batyl Alcohol
Biomimetic Barrier Matrix	Ceramide NP · Cholesterol · Stearic Acid
Nano Delivery Technology	PURISOME® Nanoliposomes

NanoActive™ BatyCer™: Biomimetic Skin Barrier Lipid Platform — PuriPharm Co. Ltd.

22 · SCIENTIFIC REFERENCES

Peer-Reviewed Foundation

01	[1] Bernal-Chávez SA, et al. Alkylglycerol Derivatives, a New Class of Skin Penetration Modulators. Molecules. 2017;22(1):185. doi:10.3390/molecules22010185
02	[2] Bektay HŞ, et al. The Design and Optimization of Ceramide NP-Loaded Liposomes to Restore the Skin Barrier. Pharmaceutics. 2023;15(12):2685. doi:10.3390/pharmaceutics15122685

FURTHER SUPPORTING LITERATURE

01	— Stratum corneum lipid organization and lamellar phase behavior
02	— Ceramide / cholesterol / free fatty acid systems and accelerated barrier recovery
03	— Liposomal topical delivery and controlled skin deposition

23 · CLOSING

NanoActive™ BatyCer™

An innovative cosmetic active platform combining biomimetic lipid science and nano delivery technology.

BIOMIMETIC SKIN BARRIER LIPID PLATFORM · PURIPHARM CO. LTD.