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.

 

 

PURIPHARM CO. LTD.

NanoActive™ Xantho

The Multi-Pathway Hop Bioactive for Skin & Scalp Longevity

INCI NAME — HUMULUS LUPULUS EXTRACT

Powered by PURISOME® Liposome Delivery Technology

XANTHOHUMOL · C21H22O5 · A PRENYLATED CHALCONE FROM HUMULUS LUPULUS

02 · POSITIONING

More Than a Botanical Antioxidant

From Hops to High-Performance Beauty Science

Xanthohumol is a prenylated chalcone naturally present in hops (Humulus lupulus L.) that connects several major biological pathways underlying visible skin aging, uneven tone, redness, blemish-prone skin and scalp stress.

NanoActive™ Xantho brings this multi-pathway biology into modern cosmetic formulation through advanced liposome delivery.

01｜Oxidative Defense:multi-ROS and singlet-oxygen quenching capacity

02｜Inflammation Control:modulation of NF-κB-driven inflammatory signaling

03｜Tone Optimization:keratinocyte–melanocyte stress communication

04｜Matrix Preservation:MMP and elastase inhibition, structural protein support

05｜Blemish Ecosystem Support:microbial, oxidative and inflammatory balance

06｜Scalp Homeostasis:a healthier foundation for scalp and hair

03 · PRODUCT PROFILE

NanoActive™ Xantho at a Glance

A Clean Technical Profile — Confirmed Information Only

Item：Product

Confirmed information：NanoActive™ Xantho

Item：INCI name

Confirmed information：HUMULUS LUPULUS EXTRACT

Item：Botanical source

Confirmed information：Humulus lupulus L.

Item：Signature bioactive

Confirmed information：Xanthohumol

Item：Bioactive family

Confirmed information：Prenylated chalcones

Item：Technology platform

Confirmed information：NanoActive™ · PURISOME® Liposome Delivery

Item：Application fields

Confirmed information：Skin Care + Scalp & Hair Care

Core Cosmetic Positioning

Antioxidant · Soothing · Tone-Evening · Anti-Aging · Blemish Care · Scalp Care

One botanical molecule. Multiple interconnected pathways of skin and scalp aging.

04 · THE MOLECULE

Xanthohumol: A Distinctive Prenylated Chalcone

Botanical Origin. Molecular Precision.

Xanthohumol combines the radical-scavenging chemistry of a polyphenol with a prenylated molecular architecture that supports interactions with lipid-rich biological environments.

Prenyl side chain: affinity for lipid-rich biological environments. Polyphenolic chalcone core: radical-scavenging chemistry.

Humulus lupulus L.: the cone of the hop plant, a natural reservoir of prenylated chalcones.

Reported Biological Activities

Reported biological activity：Antioxidant

Description：Multi-ROS defense

Reported biological activity：Antimicrobial

Description：Broad Gram-positive activity

Reported biological activity：Anti-inflammatory

Description：NF-κB pathway modulation

Reported biological activity：Pigmentation-modulating

Description：Multi-level tone pathways

Reported biological activity：ECM-protective

Description：MMP and elastase inhibition

Kołodziejczak A, et al. Int J Mol Sci. 2024;25:11938. · Oledzka E. Int J Mol Sci. 2024;25:3398.

05 · DELIVERY SCIENCE

Why Advanced Delivery Matters

Great biology meets a formulation challenge: NanoActive™ technology translates a lipophilic botanical active into a formulation-friendly format.

PURISOME® liposome concept—xanthohumol positioned within the phospholipid bilayer

Native xanthohumol：Highly lipophilic chalcone

NanoActive™ Xantho：Liposome-based incorporation strategy

Native xanthohumol：Poor aqueous solubility

NanoActive™ Xantho：Improved dispersion concept

Native xanthohumol：Challenging dispersion in water-rich cosmetic systems

NanoActive™ Xantho：Protection within a lipid-compatible microenvironment

Native xanthohumol：Delivery depends strongly on formulation environment

NanoActive™ Xantho：Designed for modern skin and scalp formulations

Native xanthohumol：—

NanoActive™ Xantho：A rational route to unlock a hydrophobic botanical active

Published research has investigated xanthohumol delivery using nanoliposomes, nanoparticles, solid lipid nanoparticles, microemulsions and other nanocarrier systems. Liposome-based delivery is a rational formulation strategy for sophisticated skin and scalp care systems.

Oledzka E. Int J Mol Sci. 2024;25:3398. · Khatib N, et al. J Food Process Preserv. 2019;43:e14075. · Harish V, et al. Pharmaceutics. 2022;14:2403.

06 · MECHANISM MAP

One Active, Multiple Beauty Pathways

A Systems Approach to Skin & Scalp Longevity

A systems approach to skin and scalp longevity

Pathway：ROS / singlet oxygen

Reported direction：Quenched ↓

Pathway：NF-κB inflammatory signaling

Reported direction：Modulated ↓

Pathway：GM-CSF / melanocyte activation

Reported direction：Suppressed ↓

Pathway：MMPs + elastase

Reported direction：Inhibited ↓

Pathway：Collagen · elastin · fibrillin

Reported direction：Supported ↑

Pathway：Acne-associated microbial pressure

Reported direction：Reduced ↓

Visible Outcomes

More resilient-looking skin · reduced appearance of redness · more even-looking tone · firmer, smoother appearance · blemish-prone skin support · healthier scalp environment.

07 · ANTIOXIDANT EVIDENCE

Antioxidant Performance Beyond Conventional Benchmarks

Exceptional Defense Against Multiple Reactive Oxygen Species

Total ORAC — Published Assay

Total ORAC: xanthohumol 4.20, green tea catechin reference 4.20, vitamin C 1.40, vitamin E 0.75

Xanthohumol delivered approximately 3× the total ORAC value of vitamin C and more than 5× that of vitamin E in this assay system.

Singlet Oxygen Absorbance Capacity — SOAC

SOAC sample：Xanthohumol

Vitamin E equivalents：14.1

SOAC sample：Green tea catechin reference

Vitamin E equivalents：1.8

SOAC sample：Vitamin E

Vitamin E equivalents：1.0

Why Singlet Oxygen Matters

Lipid oxidation · squalene peroxidation · photo-oxidative stress · inflammatory amplification · visible aging.

Yamaguchi N, Satoh-Yamaguchi K, Ono M. Phytomedicine. 2009;16:369–376. DOI: 10.1016/j.phymed.2008.12.021.

08 · INFLAMMATION CONTROL

Breaking the Oxidative–Inflammatory Loop

Calm the Signals That Accelerate Visible Aging

Xanthohumol—Interrupts the Cascade

Environmental / UV stress→ROS generation→TLR4 / MD2—NF-κB activation

→TNF-α · IL-1β · IL-6 · IL-12 · NO→Redness · irritation · ECM degradation · uneven appearance

Published Evidence

Suppression of NF-κB-related inflammatory signaling; reduced IL-12 production; reduced nitric oxide production; modulation of TNF-α, IL-1β and IL-6 signaling; and reduced chronic inflammatory response in experimental skin models.

Designed to help move stressed skin from inflammatory reactivity toward visible equilibrium.

Cho Y-C, et al. Int Immunopharmacol. 2010;10:556–561. · Philips N, et al. Anti-Inflamm Anti-Allergy Agents Med Chem. 2010;9:142–149. · Kołodziejczak A, et al. Int J Mol Sci. 2024;25:11938.

09 · TONE SCIENCE｜GM-CSF

Interrupting Keratinocyte-to-Melanocyte Stress Signaling

GM-CSF—A Distinctive Skin-Stress Target

UV and chemical stress activate epidermal keratinocytes→Stressed keratinocytes release GM-CSF→Melanocyte activation and stress-associated pigmentation signaling

Reduction of Stress-Induced GM-CSF Release—In Vitro

PMA-induced stress −48%; UVB-induced stress −21%

Stress model：PMA-induced stress

With xanthohumol：52% of control, a 48% reduction

Positive-control context：57% reduction

Stress model：UVB-induced stress

With xanthohumol：79% of control, a 21% reduction

Positive-control context：45% reduction

Targeting the communication between stressed keratinocytes and melanocytes.

Patent-reported keratinocyte data: WO2010044076.

10 · TONE SCIENCE｜EX VIVO

Ex Vivo Human Skin: Keeping the UV Stress Signal Near Baseline

A Compelling Keratinocyte–Melanocyte Story

Study element：Model

Detail：Human skin explants

Study element：Donor panel

Detail：n=6 donors

Study element：Skin phototype

Detail：Phototype III

Study element：Stress induction

Detail：UVA + UVB challenge

Active melanocytes: baseline 5.6, UVAB 10.5, UVAB + xanthohumol approximately basal

Endpoint：GM-CSF release

Baseline：5.35 pg/mL

UVAB：approximately 4× baseline

UVAB + xanthohumol：6.95 pg/mL

Endpoint：Active melanocytes

Baseline：5.6

UVAB：10.5

UVAB + xanthohumol：approximately basal

Xanthohumol helped disconnect UV stress from melanocyte activation.

Patent-reported ex vivo human skin data: WO2010044076.

11 · TONE SCIENCE｜MULTI-LEVEL

More Than Tyrosinase: Multi-Level Tone Optimization

Target Pigmentation Across the Epidermal Signaling Network

01｜Signal—GM-CSF stress-signal control:reduced keratinocyte-driven melanocyte activation following UV stress

02｜Synthesis—melanogenic enzyme modulation:published mushroom tyrosinase studies demonstrate potent inhibition of L-tyrosine and L-DOPA oxidation

03｜Transfer—reduced melanocyte dendricity:reported decrease in dendrite number and length, potentially reducing pigment transfer

04｜Clearance—melanosome clearance:published cell studies indicate enhanced melanosome degradation in keratinocytes

From pigment signaling to pigment transfer and clearance—a multi-level approach to visible tone uniformity.

Goenka S, Simon SR. Biochem Biophys Rep. 2021;26:100955. · Kołodziejczak A, et al. Int J Mol Sci. 2024;25:11938. · WO2010044076.

12 · HUMAN EVIDENCE

Human Use Data: Visible Tone Evening in 8 Weeks

Patent-Reported Human Cosmetic Study

Study Design

25 female subjects; mean age 34.1 ± 6.1 years; phototypes III–IV; twice-daily application for 8 weeks; test cream containing 3% P1 xanthohumol preparation, equivalent to 22.5 ppm xanthohumol. Measurements included L*, ITA°, redness a* and pigmented-spot morphology.

Result：Objective brightness / ITA° criteria

Finding：68–72% of subjects demonstrated improvement after 8 weeks

Result：Pigmented spot area

Finding：−12.6% after 8 weeks

Result：Visible redness

Finding：Significantly reduced after 8 weeks

Visible tone uniformity backed by human cosmetic-use data.

Patent-reported human-use data: WO2010044076. Not proprietary NanoActive™ Xantho clinical testing.

13 · MATRIX LONGEVITY

Defending the Youthful Extracellular Matrix

Protect What Gives Skin Its Strength and Elasticity

Matrix Synthesis ⇌ Matrix Degradation

Slows degradation：Inhibits MMP-1, MMP-2, MMP-8, MMP-9 and elastase

Supports structural renewal：Published fibroblast data report increased biosynthesis of collagen I, III and V, elastin, fibrillin-1 and fibrillin-2

Slows degradation：MMP-1 inhibition: 91% at 100 µg/mL MMP-8 inhibition: 99% at 100 µg/mL

Supports structural renewal：Structural proteins associated with skin strength and elasticity

Slows degradation：Reported IC50: MMP-1 20.5 µg/mL; MMP-8 16.8 µg/mL

Supports structural renewal：—

Dual-action matrix strategy—slow degradation while supporting structural renewal.

Yamaguchi N, et al. Phytomedicine. 2009;16:369–376. · Philips N, et al. J Cosmet Sci. 2010;61:125–132.

14 · BLEMISH CARE

A Multi-Target Active for Blemish-Prone Skin

Beyond Antibacterial: Rebalancing the Blemish Ecosystem

Target：Microbial pressure

Direction：Acne-associated bacteria ↓

Target：Oxidative stress

Direction：ROS and singlet oxygen ↓

Target：Inflammatory signaling

Direction：COX-2 / PGE2 / IL-1β / TNF-α-associated pathways ↓

Target：Matrix stress

Direction：MMP-driven collagen degradation ↓

Published MIC Values—µg/mL

MIC values: C. acnes 3 µg/mL; S. aureus 1; S. epidermidis 3; S. pyogenes 1

Organism：C. acnes

Published MIC, µg/mL：3

Organism：S. aureus

Published MIC, µg/mL：1

Organism：S. epidermidis

Published MIC, µg/mL：3

Organism：S. pyogenes

Published MIC, µg/mL：1

Cutibacterium acnes was reported as Propionibacterium acnes in the original study.

Antioxidant + antimicrobial + inflammation-modulating + matrix-protective activity in one botanical platform.

Yamaguchi N, et al. Phytomedicine. 2009;16:369–376.

15 · SCALP & HAIR CARE

Scalp-First Hair Care

Healthy-Looking Hair Starts with Scalp Homeostasis

Scalp and follicular microenvironment—oxidative, sebum and microbial stress signals

01｜Oxidative-Stress Defense:helps counter environmental and photo-oxidative stress affecting the scalp

02｜Scalp Comfort:supports modulation of inflammatory signaling associated with visible redness and discomfort

03｜Sebum Environment Support:hop and xanthohumol literature supports sebum-conscious cosmetic concepts

04｜Microbial-Balance-Oriented Care:broad activity against relevant Gram-positive microorganisms supports scalp-purifying concepts

05｜Follicular Environment Protection:helps maintain a healthier biochemical environment around the scalp and follicular opening

A scalp-first active for stronger skin foundations and healthier-looking hair.

WO2010044076 describes topical xanthohumol applications for improving the overall condition of skin and scalp.

16 · APPLICATIONS

Formulation & Application Opportunities

From High-Performance Facial Care to Advanced Scalp Systems

Skin Care：Antioxidant serums; tone-evening essences; anti-aging concentrates

Scalp & Hair Care：Scalp serums; scalp tonics; scalp essences

Skin Care：Blemish-prone skin serums; post-stress soothing products; redness-care formulations

Scalp & Hair Care：Sebum-conscious scalp care; sensitive-scalp formulas; anti-pollution scalp care

Skin Care：Urban defense / anti-pollution care; after-sun skin care

Scalp & Hair Care：Premium shampoos; conditioners; leave-on scalp treatments

Skin Care：Eye and facial care; premium night-repair products

Scalp & Hair Care：Hair-density appearance support concepts*

*Based on scalp health.

Suitable for development across sophisticated leave-on and rinse-off skin and scalp formats.

17 · THE NANOACTIVE™ XANTHO ADVANTAGE

One Active. Six Strategic Beauty Territories.

01｜Antioxidant Shield:multi-ROS and singlet-oxygen defense

02｜Redness & Comfort:multi-pathway inflammatory-signaling modulation

03｜Even-Tone Science:GM-CSF, melanocyte activation, pigment transport and melanosome pathways

04｜Matrix Longevity:MMP / elastase inhibition plus structural-protein support

05｜Blemish Ecosystem:antimicrobial, antioxidant, inflammatory and matrix approach

06｜Scalp Homeostasis:oxidative, inflammatory, sebum and microbial-environment support

Multi-Pathway Botanical Intelligence, Delivered by Liposome Science.

NanoActive™ Xantho transforms the biological versatility of hop-derived xanthohumol into a modern active platform for next-generation skin and scalp care.

18 · EVIDENCE BASE

Selected Scientific References

Human & Ex Vivo Evidence · Primary Mechanistic Data · High-Quality Reviews

01｜Yamaguchi N, Satoh-Yamaguchi K, Ono M. In vitro evaluation of antibacterial, anticollagenase, and antioxidant activities of hop components addressing acne vulgaris.Phytomedicine.2009;16:369–376. DOI: 10.1016/j.phymed.2008.12.021.

02｜Philips N, Samuel M, Arena R, et al. Direct inhibition of elastase and matrix metalloproteinases and stimulation of biosynthesis of fibrillar collagens, elastin, and fibrillins by xanthohumol.J Cosmet Sci.2010;61:125–132.

03｜Cho YC, You SK, Kim HJ, et al. Xanthohumol inhibits IL-12 production and reduces chronic allergic contact dermatitis.Int Immunopharmacol.2010;10:556–561.

04｜Goenka S, Simon SR. Depigmenting effect of xanthohumol from hop extract in MNT-1 human melanoma cells and normal human melanocytes.Biochem Biophys Rep.2021;26:100955.

05｜Kołodziejczak A, Dziedzic M, Algiert-Zielińska B, et al. A Novel Look at Mechanisms and Applications of Xanthohumol in Dermatology and Cosmetology.Int J Mol Sci.2024;25:11938. DOI: 10.3390/ijms252211938.

06｜Oledzka E. Xanthohumol—A Miracle Molecule with Biological Activities: A Review of Biodegradable Polymeric Carriers and Naturally Derived Compounds for Its Delivery.Int J Mol Sci.2024;25:3398. DOI: 10.3390/ijms25063398.

07｜Gerhäuser C. Broad spectrum antiinfective potential of xanthohumol from hop in comparison with activities of other hop constituents and metabolites.Mol Nutr Food Res.2005;49:827–831.

08｜WO2010044076. Cosmetic and topical uses of xanthohumol, including skin brightening, reduction of skin redness and GM-CSF-related mechanisms.

Evidence hierarchy: human / ex vivo cosmetic evidence → primary peer-reviewed mechanistic data → high-quality scientific reviews.