Enhanced bioavailability of skin whitening actives in topical applications

Contents

Objective

To understand different strategies used for enhancing the bioavailability of skin whitening agents in topical applications by various companies.

Scope


Search methodology

Search strategy 1. Various keywords were retrieved for conducting the search related to enhanced bioavailability of active ingredients in topical applications for skin whitening from pubmed MESH, relevant patents, scientific articles and thesaurus.
2.Various Class-codes have been retrieved from relevant patents and their citations. Also . (Refer section 4).
3.The database used for patent search is Thomson innovation.
Keywords Whitening, lightening, topical, depigmentation, bioavailability, penetration enhancer etc.

Introduction

Skin whitening/lightening/brightening is an important skin care need, especially in the asian population. Whitening skin care is a process in which the darker skin is prepared to look lighter. Human skin color determined from the outermost layer of the skin, the epidermis where the pigment-producing cells melanocytes are localized to produce melanin. The amount of melanin synthesized by the melanocyte, and its distribution pattern in the surrounding keratinocytes, determines the actual color of the skin. Melanin forms through a series of oxidative reactions involving the amino acid tyrosine in the presence of the enzyme tyrosinase.Parvez et al,2006

Elimination of melanin can be done in three ways:

Hydroquinone and hydroxyanisole, in the past, were the standard ingredient for skin lightening treatments. However with reports of potential mutagenicity, there has been an increasing impetus to find alternative herbal and pharmaceutical depigmenting agents.

Current trends in skin whitening ingredients

Great advances have been made to understand pigment biology and the processes underlying skin pigmentation in the last decade. Many researchers have begun to produce natural alternatives which mimic the skin lightening properties of hydroquinone and hydroxyanisole. Ingredients such as kojic acid and licorice have become quite popular along with more advanced ingredients like Alpha-Arbutin. When combined, these ingredients can often produce better results that even surpass hydroquinone but without the associated risks. Below is the list of commonly used ingredients that are widely used for skin whitening.

Skin whitening ingredients and enhanced bioavailability

Bioavailability

The determination of the bioavailability of systemically absorbed products is defined as the rate and extent to which the active ingredient or active moiety is absorbed from the drug product and becomes available at the site of action Kanfer and Shargel, 2008. However, when considering products which contain active ingredient(s) not intended for systemic absorption, the US FDA, published the following statement in the US Federal Register (US Federal Register, 2009) where such products?...... may be assessed by (surrogate) measurements intended to reflect the rate and extent to which the active ingredient or moiety becomes available at the site of action?.


Many skin-lightening actives have problems with lesser bioavailability or instability during storage, it also have low affinity to the skin and have little percutaneous absorption. Therefore, several attempts have successfully been made to synthesize conjugates to improve their bioavailabilities. Novel technology has shown great potential for improving the effectiveness and efficiency of delivery of ingredients, e.g.

Researcher also used skin penetration enhancer, volatile silicone and several other organic compound which make the ingredients stable and more bioavailable to the skin.

Concept table

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Search strategy

S.No Concept Scope Search strategy Hits
1 Class codes of skin whitening AND keywords of bioavailability(English) Full patent spec. (424062) OR (424449) OR **** ###
2 Class codes of skin whitening AND keywords of bioavailability(German) Full patent spec. (A61Q001902) AND (((Bioverfügbarkeit OR **** ###
3 Class codes of skin whitening AND keywords of bioavailability(French) Full patent spec. (A61Q001902) AND (((biodisponibilité OR **** ###
4 F terms of skin whitening AND keywords of bioavailability (English) full spec in japanese only (4C083EE16) AND ((Bioavailabilit*3 OR **** ###
5 Combined query (Class code of skin whitening and key words of bioavailability) 1 OR 2 OR 3 or 4 ###
6 highly relevant class codes of bioavailability and keywords of skin whitening Claims, Title, Abstract ((514946) OR (514947) OR **** ###
7 Class codes of bioavailability AND key words of skin whitening(English) Claims title abstract (5140011) OR (5140022) OR **** ###
8 english keywords and japanese f terms for bioavailability Claims title abstract (4C076FF34) OR (4C076FF03) OR **** ###
9 Combined query(Class codes of bio-availability and key words of skin whitening) 6 OR 7 OR 8 ###
10 Combined query (key word - classcode search) 5 or 9 ###
11 Skin whitening AND bioavailability key words(English) Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability (((Skin*1 OR*3 derm*2 OR **** ###
12 Class codes of bioavailability AND key words of skin whitening(Geman) Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability (((Haut OR pelle OR **** ###
13 Class codes of bioavailability AND key words of skin whitening(French) Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability ((((la ADJ2 peau) OR peau OR **** ###
14 Combined query (keyword search) 11 OR 12 OR 13 ###
15 Combined query (Kewyword search and keyword - Classcode search) 10 OR 14 ###
16 Key words for irrelevant patents Title, Abstract (Teeth OR tooth OR**** ###
17 Final query 15 NOT 16 ###
18 L?Oreal Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment "La Institut Lancome" OR **** ###
19 L?Oreal Restricted 17 AND 18 ###
20 Shiseido Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment "SHISEIDO INTERNATIONAL FRANCE" OR **** ###
21 Shiseido Restricted 17 AND 20 ###
22 Kao and Kanebo Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment "LABTEC GESELLSCAFT FA?R TECHNOLOGISCHE FORSCHUNG UND ENTTWICKLUNG MBH" OR**** ###
23 Kao and kanebo restricted 17 AND 22 ###

Relevant class codes and definitions

IPC/ECLA classes

A61 Medical or Veterinary science; Hygiene Column1 Column2
A61Q Use of cosmetics or similar toilet preparation
A61Q 19/02 Preparations for care of the skin =>for chemically bleaching or whitening the skin
**** **** ****

US Classes

424 Drug, bio-affecting and body treating compositions Column1
424/62 Bleach for live hair or skin (e.g., peroxides, etc.)
424/78.03 Topical body preparation containing solid synthetic organic polymer as designated organic active ingredient (doai) => Skin cosmetic coating
**** ****

F-Term

Theme Title of the theme F-term F-term description
4C083 Cosmetics 4C083EE16 Whitening (Tyrosinase inhibition, melanin inhibition)
4C076 Medicinal preparation 4C076FF34 Absorption accelerators or penetrants
**** **** **** ****

Taxonomy

Tax.jpg

Relevant patents

S.No Patent / Publication No. Title Assignee/Applicant Date of Publication Problem Solution
1 US5874095A Enhanced skin penetration system for improved topical delivery of drugs Richardson Vicks Inc. 2/23/1999 Poor penetration of many drugs across the epidermal lipid barrier has, until now, frustrated attempts to deliver clinically significant doses of many drugs by the topical route.
Compositions provides containing a skin penetration enhancing vehicle with insufficient transdermal penetration
Orally administered drugs can increase the dosage required to achieve therapeutic levels and thereby increase undesirable side effects
Composition containing a pharmaceutical active(hydroquinone, ascorbic acid, kojic acid and sodium metabisulfite)and polyacrylamide which enhances the skin penetration of drugs.

Provide sufficient skin penetration enhancement to achieve therapeutic levels of the drugs in target internal tissues.Compositions with low dermal irritation, especially in compositions requiring a low pH.

Compositions having good stability.
2 US20090162305A1 Formulations of low oil content comprising diphenylmethane derivatives Symrise GmbH & Co. KG 6/25/2009 Sensitive to oxidation and can be stabilized in cosmetic formulations only with difficulty, inadequate action on the skin, high sensitizing potential and causes contact allergies,no reference having a defined content of an oily phase is to be found with less bioavailability Novel specific (cosmetic) formulations for improving the bioavailability and activity of skin- or hair-lightening agent as diphenylmethane derivatives (tyrosinase inhibitors) commmonly known as styrylresorcinol which has more stbility and little toxicity.
3 ***** **** **** **** **** ****

Analysis

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Trends and Insights

Assigneewise preferred skin whitening actives

Skin-whitening actives vs Assignees

Key Points

Assignee-wise adopted bioavailability enhancing strategies

Bioavailability enhancing strategies vs Assignees

Key Points

Preferred solvent with respect to penetration enhancer

Penetration enhancer (x-axis) vs solvent (z-axis)


Key Points

Delivery strategies for whitening actives

DELIVERY STAT.jpg

Dashboard

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Enhanced bioavailability of skin-whitening ingredients in topical applications