Lipid knowledge for the personal care industry

Bioactive lipids and skin health

Jari Alander

2019

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Skin properties and challenges

– Moisturization

– Stress conditions

Bioactive lipophilic components

– Tocopherols & phytosterols

– Triterpene esters

Lipids and skin healthContent

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The skin is our largest organ with different properties in different sites of the body

The skin reflects our general well-being and emotions

The skin is the barrier between the environment and our bodies

A good skin care regime will help to…

– Protect: reduce the risk of skin disorders and increase skin resilience

– Enhance skin repair: the skin regenerates and preserves youthful appearance

– Reduce wrinkling: well moisturized skin is firmer and more elastic and reduces wrinkling

– Give pleasure/indulgence: skin in good condition feels better and make you feel better and more confident

Why should you take goodcare of your skin?

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Prevents water loss and protects against external aggression

The barrier lipids form a tight lamellar barrier surrounding the corneocytes.

Lipid organization influences barrier efficiency and water transport in SC

Alternating hydrophilic and lipophilic domains polar regions allowing

water passage

Stratum corneum structure and function– the brick and mortar model

3D-structure of stratum corneum lipid bilayers (L. Norlén) shows highlystructured but flexible composition

Desmosomes

Corneocytes

Intercellularlipid layer

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Main parameters contributing to skin barrier quality:

– Stratum corneum thickness

– Balance between desquamation and replenishing of corneocytes is critical

– Intercellular lipid content and organization

– Derived from keratinocytes and secreted from lamellar bodies

– Includes: ceramides ~40%, free fatty acids ~25%, cholesterol ~25%

– Sebum production

– Varies depending on age, sex and skin area

– Forms a hydrolipidic layer

– Includes: triglycerides, wax esters, squalene, FFA, cholesteryl esters

The skin barrier and age

Degeneration of SC barrier

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Keep moisture inside by enhancing the Natural Moisturizing Factor by using humectants

– Glycerol, urea and similar hydrophilic compounds

Create a barrier on top of the skin to prevent evaporation

– Film forming agents, petrolatum, shea butter

Enhance the epidermal barrier

– Actives, linoleic acid, improve ceramide synthesis

Avoid breakdown of the skin barrier

– Milder ingredients in general

– Protect against environmental damage

Four principal mechanisms for increasing skin moisture

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Short term

– Reduced TEWL and improved hydration

– Counteract dehydration from soaps and surfactants

Medium term

– Counteract impairment in corneocyte maturation and desquamation

Long term

– Strengthened SC barrier function and improved water holding capacity

Effect of skin care products on the stratum corneum and epidermis

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There is no legal definition of dermocosmetics!

– Dermocosmetics are skincare products that contain actives to reduce or enhance the symptoms of various skin conditions

The dermocosmetic market grows substantially faster than traditional skin care and is therefore seen as an attractive direction for new developments

Dermocosmetics are usually…

– Well substantiated for activity and function

– Formulated to have very low skin irritating potential

– Designed for protection, soothing, anti-irritant and moisturizing capabilities

– Perceived as safer, purer and more effective

Beyond moisturization: Dermocosmetics

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Efficacy ~ Activity*Availability

– Activity depends on substance structure and mechanism of action

– Availability depends on substance structure but also formulation parameters

Bioavailability can be influenced by formulation if the solubility of the active is controlled

– Water, emollients and emulsifiers control solubility in the interface between the formulation and the skin

Low uptake through skin is expected for large molecules (MW>500 Da) and either very hydrophilic or very lipophilic substances (log Pow below -1 or above 4) (SCCS/1501/12 p23)

– Presence of penetration enhancers is common in cosmetic formulations, either unintended or intentionally added

General considerations ofbioactivity of actives

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How can bioactive lipids protect against environmental stress and free radicals?

FR: Free radicalsROS: Reactive oxygen species

TocopherolsInactivate FR and ROSDecrease damage caused by ROS/FR Protecting cellular organelles, lipids, tocopherols, proteins and DNAReducing formation of proteases

Cyclo-oxygenase and lipoxygenase mediated inflammatory reactions

Tocopherols and sterols/triterpenes Regulate anti-inflammatory reactionsRepair by fine-tuning immune activation

UVA/UVB radiationChemicalsEnvironmental pollutantsMicro-organisms

Enzymatic and non-enzymatic antioxidant system

FR + ROS

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Lipex PreAct™ INCI (EU): Canola oil

– Low in polyunsaturated (7% C18:2) and high in monounsaturated fatty acids (80% C18:1)

– Minimized risk of lipid peroxide formation, thus high stability against photo-oxidation

– Good heat and oxidation stability → OSI (@110°C)>100 hours

& long shelf life

Canola oil rich in tocopherol and phytosterols

Lipex PreAct™ - Typical content (ppm)

α-tocopherol (anti-oxidant) 400

γ-tocopherol (anti-inflammatory) 600

Phytosterols; β-sitosterol, campesterol, brassica- and avenasterols (anti-inflammatory)

9000

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Anti-oxidant efficacy of Lipex PreAct™measured: carbonyl protein formation – marker of protein oxidation

Lipex PreAct™ protects reconstructed human epidermis cells, expressed as the reduction of carbonyl protein formation.

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Soothing properties of Lipex PreAct™

Clinical study of anti-irritative properties on surfactant-irritated skin

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Lipex SheaTris™ INCI (EU): Butyrospermum parkii butter extract

Bioactive shea butter extractTriterpene ester content 50–65%

FunctionalityStrengthens skin barrier

– Protection against dry skin conditions

Protection against environmental stress

– Helps to fight premature aging

PropertiesOil soluble activeEasy to formulate: use level ± 1 %Well characterized and safe use

Shea butter extract rich in triterpenes

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Triterpene esters from shea butter

Triterpene ester compositionCinnamates: 50–55 % Acetates: 40–45 %Fatty acid esters: 2–7%

α-Amyrin

(~27%)

Butyrospermol

(~25%)

Parkeol

(~5%)

Lupeol

(~22%)

ß-Amyrin

(~10%)

Triterpenes: MW ~ 400 Da, Log Pow ~6

HOHO

HOHOHO

Acetic acid

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Anti-inflammatory properties from shea butter triterpenes*

*Akihisa et al. Inhibitory effect of triterpene esters from shea butter on TPA-induced inflammation in mice. J. Oleo Sci. 59, (6) 273-280 (2010)

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Anti-inflammatory properties of shea butter triterpene esters

Documented properties

UV-stressEx vivo; Lipex SheaTris™ cream(0,3% triterpenes) UV-exposure D6.- 59% release of PGE-2 - 16% release of TNF-αvs non treated explants, D7.

Chemical stressIn vitro; on human epidermal keratinocytes, exposed to Croton oil. Shea butter extract vs hydrocortisone. - 25% release of IL 1- cytokine

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Skin barrier strengthening propertiesof shea butter triterpene esters

Documented properties

- Increased epidermal thickness- 26% increase vs placebo cream

(p<0,05), evaluated after 6 days ex vivo- Cream including 0,3% triterpene esters

(0,5% Lipex SheaTris™)

Lipex SheaTris™ cream resulted in a thickand well laminated SC and epidermis presenting 7-8 cellular layers with a goodmorphology

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Skin protecting properties ofshea butter triterpene esters

Documented properties

- Stimulated formation of fibroblasts- in vitro, 80% vs control

- Increase of dermal collagen- ex vivo, 6% increase of dermal collagen

vs placebo and control, D6.

- Reduced collagenase activity- ex vivo, 30% decreased activity vs

placebo- in vitro, 66% decreased MMP-3 gene

expression vs control

Lipex SheaTris™ cream;0.5% Lipex® SheaTris™ (0.3% TE)

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Target action: reducing expression of biomarkers involved in extrinsic skin aging

Three formulations with 0, 0.5 and 1.0% Lipex SheaTris™ were tested in an in-vitro model for pollution induced skin aging

Reconstructed Human Epidermis (RHE) and Human Dermal Fibroblasts (NDHF) were treated with the formulations prior to exposure to standardized urban dust according to standard procedures

4 biomarkers for inflammation (IL-1a, IL-6, IL-8 and TNF-a) were quantified from the RHE based test

mRNA expression of ELN & MMP-1 (extracellular matrix elasticity and remodeling) as well as COX-2 & INOS (inflammatory response) were quantified to further investigate the effectiveness of the formulations to decrease pollution induced skin aging

Dexamethasone was used as benchmark for RHE study while carnosinicacid was used for the gene expression study

All values were compared against untreated cells (exposed to urban dust but not pre-treated with the formulations or with the benchmark)

Skin aging induced by urban dust: Study design

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Skin aging induced by urban dustReconstructed Human Epidermis pre-treated with formulationsprior to exposure to standardized urban dust.

Formulations with 0.5–1.0% Lipex SheaTris™ significantlydecrease the release of TNF-a and other relevant biomarkers

TNF-a

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Lipex SheaTris™ also has a significant effect on the COX-2/INOS mediated routes of skin aging

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The urban dust study shows that triterpenes in Lipex SheaTris™

– have a significant effect on several biomarkers for urban dust induced skin aging

– have potential for decreasing damage on skin caused by urban pollution

The test confirms the previous studies and the mechanism of the protective and soothing effects of shea butter triterpenes on the skin damage caused by environmental stress (including chemical stress, UV stress and urban dust)

Conclusions – Lipex SheaTris™

in pollution protection

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SummaryAAK lipids helps to improve skin properties and the barrier function

Lipid class Functionality

Triglycerides Moisturizing and softening

Fatty acids Essential part of complex lipids and skin barrierPrecursors of bioactive mediators

Tocopherols Anti-oxidants

Anti-inflammatory agents

Phytosterols Membrane constituents

Anti-inflammatory agents

Triterpenes Anti-inflammatory agents

Inhibitors of proteases

Promote skin cell renewal

© 2019 AAK Sweden ABNo part of this presentation may be reproduced in any form or by any means without the prior written permission of AAK Sweden AB. Disclaimer: This presentation is intended for educational purposes only. AAK Sweden AB shall not be liable for any third-party claims or losses of any nature, including, but not limited to, lost profits, punitive or consequential damages.

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