Changes
=Objective=
To understand different strategies used for enhancing the bioavailability of skin whitening agents in topical applications by various companies.
=Scope=
* This report is restricted to four major players in this technology area- Kao, L'Oreal, P&G and Shiseido.
* We have taken patents as a source of information to understand different methods for enhancing bioavailability.
=Search methodology=
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FCD5B4"|'''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.<br>2.Various Class-codes have been retrieved from relevant patents and their citations. Also . (Refer section 4).<br>3.The database used for patent search is Thomson innovation.
|-
|align = "center" bgcolor = "#FCD5B4"|'''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.[http://www.ncbi.nlm.nih.gov/pubmed/16841367 Parvez et al,2006]
Elimination of melanin can be done in three ways:
*Suppressing Tyrosinase formation
*Inhibiting Tyrosinase activity
*Reduction of Melanin
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.
[[Image:table1.jpg|850px|thumb|center|[http://onlinelibrary.wiley.com/doi/10.1111/j.1468-2494.2010.00616.x/full Gillbro & Olsson,2011]]]
*Because of the accessibility and large area of the skin, it has long been considered as promising route for the administration of drugs, where dermal, regional, or systemic effects are desired. The advantages of the topical route of drug administration include: avoidance of the risks and inconvenience of parenteral treatment; avoidance of the variable absorption and metabolism associated with oral treatment; continuity of drug administration, permitting use of pharmacologically active agents with short biological half-lives and potential reduction of gastrointestinal irritation in systemic administration.[http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN%2F5874095 Deckner et al,1999]
*However, the impermeability of skin is well-known, serving as a barrier to ingress of pathogens and toxic chemicals, and egress of physiologic fluids. This impermeability is the result of normal physiologic changes in developing skin,also results in lesser bioavailability.It is already well known that bioavailability of compounds taken topically example skin whitening ingredients are always lesser than that taken orally or intravenously. Bioavailability of topical dosage forms not intended for absorption has proved to be quite difficult, daunting and extremely challenging.
==Skin whitening ingredients and enhanced bioavailability==
===Bioavailability===
[[Image:Bioavailability.jpg|500px|thumb|right|[http://www.spitalpharmazie-basel.ch/pdf/Diss_Pellanda.pdf Schematic depiction of percutaneous absorption,Pellanda(2006)]]]
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 [http://www.omicsonline.org/0975-0851/JBB-02-102.pdf 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.
*Microemulsion- An oil-in-water microemulsion have the ability to encapsulate non polar molecules such as lipids, flavorants, antimicrobials, antioxidants, and vitamins, it formulated using lecithin and an alkyl glucoside. It was proposed as a cosmetic vehicle for arbutin and kojic acid, naturally occurring whitening agents. The stability of these compounds are higher in microemulsion than in aqueous solutions.[http://www.ncbi.nlm.nih.gov/pubmed/15131725 Gallarate et al,2004]
*Liposomes- Liposomes encapsulate water and lipid-soluble pharmacologically and cosmetically active components. Liposomes favor the disposition of encapsulated active ingredients in the epidermis and dermis, while the permeation rate is decreased. This helps to fix active ingredients to the outermost skin layers as desired for cosmetic products.[http://www.ncbi.nlm.nih.gov/pubmed/15989590 Cevec,1997]
*Nanoemulsions- Nanoemulsions are emulsions having small droplet size (20–300nm). They could be used for lipophilic as well as hydrophilic substances with enhanced bioavailability
[[Image:newer approach2.jpg|850px|thumb|center|[http://www.ncbi.nlm.nih.gov/pubmed/18482010 Chanchal & Swarnalata,2008]]]
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=
[[Click here to view concept table]]
=Search strategy=
*'''Database: Thomson Innovation'''
*'''Coverage:US Grant, GB App, US App, FR App, WO App, DE Util, EP Grant, DE Grant, EP App, DE App, JP Util, JP Grant, JP App, CN Util, CN App, KR Util , KR Grant, KR App, Other, DWPI'''
*'''Time Line:1836 - 19 January 2012'''<br />
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FAC090"|'''S.No'''
|align = "center" bgcolor = "#FAC090"|'''Concept'''
|align = "center" bgcolor = "#FAC090"|'''Scope'''
|align = "center" bgcolor = "#FAC090"|'''Search strategy'''
|align = "center" bgcolor = "#FAC090"|'''Hits'''
|-
|align = "center" bgcolor = "#FAC090"|'''1'''
|align = "center"|'''Class codes of skin whitening AND keywords of bioavailability(English)'''
|align = "center"|Full patent spec.
|align = "center"|(424062) OR (424449) OR (514844) OR (42407803) OR (4C083EE16)OR (A61Q001902) AND ((Bioavailabilit*3 OR (Bio*9 ADJ2 availab*7) OR (Physiologic*2 ADJ2 availab*7) OR (availabilit*3 ADJ2 equivalenc*3)) OR ((Enhanc*4 OR increas*3 OR high*2 OR improv*4 OR promot*3 ) NEAR10 (absor*4 OR permeab*5 OR penetrat*4)))
|align = "center"|5885
|-
|align = "center" bgcolor = "#FAC090"|'''2'''
|align = "center"|'''Class codes of skin whitening AND keywords of bioavailability(German)'''
|align = "center"|Full patent spec.
|align = "center"|(A61Q001902) AND (((Bioverfügbarkeit OR bioverfügbarkeiten OR ((Bio OR biologisch OR biologisch) ADJ2 (Verfügbarkeit OR verfügbar))) OR (((physiologisch OR physiologisch) ADJ2 (Verfügbarkeit OR verfügbar)) OR (Verfügbarkeit ADJ2 Gleichwertigkeit))) OR ((Verbesserung OR verbessern OR erhöhen OR erhöht OR erhöht OR erhöhen OR hoch OR verbessern OR verbessert OR Verbesserung OR fördern OR gefördert OR Förderung) NEAR10 (Absorption OR absorbiert OR durchlässig OR Durchlässigkeit OR durchdringen OR Penetration OR eingedrungen)))
|align = "center"|50
|-
|align = "center" bgcolor = "#FAC090"|'''3'''
|align = "center"|'''Class codes of skin whitening AND keywords of bioavailability(French)'''
|align = "center"|Full patent spec.
|align = "center"|(A61Q001902) AND (((biodisponibilité OR biodisponibilités OR ((Bio OR biologique OR biologiquement) ADJ2 (la disponibilité OR disponibles))) OR (((physiologiques OR physiologiquement) ADJ2 ((la ADJ2 disponibilité) OR disponibles)) OR ((la ADJ2 disponibilité) ADJ2 equivalenc*3))) OR ((amélioration OR améliorer OR (augmentation ADJ2 de) OR augmente OR augmenté OR augmenter OR haute OR hautement OR (améliorer ADJ2 la) OR améliorée OR l<nowiki>’</nowiki>amélioration OR (promouvoir ADJ2 la) OR promu OR (la ADJ2 promotion)) NEAR10 (d<nowiki>’</nowiki>absorption OR absorbés OR perméables OR (la ADJ2 perméabilité) OR pénètrent OR (la ADJ2 pénétration) OR pénétré)))
|align = "center"|105
|-
|align = "center" bgcolor = "#FAC090"|'''4'''
|align = "center"|'''F terms of skin whitening AND keywords of bioavailability (English)'''
|align = "center"|full spec in japanese only
|align = "center"|(4C083EE16) AND ((Bioavailabilit*3 OR (Bio*9 ADJ2 availab*7) OR (Physiologic*2 ADJ2 availab*7) OR (availabilit*3 ADJ2 equivalenc*3)) OR ((Enhanc*4 OR increas*3 OR high*2 OR improv*4 OR promot*3 ) NEAR10 (absor*4 OR permeab*5 OR penetrat*4)))
|align = "center"|445
|-
|align = "center" bgcolor = "#FAC090"|'''5'''
|align = "center" colspan = "2"|'''Combined query (Class code of skin whitening and key words of bioavailability)'''
|align = "center"|1 OR 2 OR 3 or 4
|align = "center"|5973
|-
|align = "center" bgcolor = "#FAC090"|'''6'''
|align = "center"|'''highly relevant class codes of bioavailability and keywords of skin whitening'''
|align = "center"|Claims, Title, Abstract
|align = "center"|((514946) OR (514947) OR (4C076FF34)) AND ((Whiten*3 OR lighten*3 OR brighten*3 OR fair*4 OR depigment*5) OR ((Inhibit*3 OR reduc*4 OR anti OR suppress*4 OR decreas*4 OR block*3) NEAR10 (Tyrosinase OR melan*8 OR melasma OR chloasma OR suntan OR (solar ADJ2 lentig*) OR pigment*5)))
|align = "center"|278
|-
|align = "center" bgcolor = "#FAC090"|'''7'''
|align = "center"|'''Class codes of bioavailability AND key words of skin whitening(English)'''
|align = "center"|Claims title abstract
|align = "center"|(5140011) OR (5140022) OR (514946) OR (514947) AND (((Skin*1 OR*3 derm*2 OR (stratum ADJ2 corneum) OR (stratum lucidum) OR (stratum granulosum) OR (stratum spinosum) OR (stratum basale) OR topical*2) NEAR20 (Whiten*3 OR lighten*3 OR brighten*3 OR fair*4 OR depigment*5)) OR (Skin*1 AND depigment*) OR ((Inhibit*3 OR reduc*4 OR anti OR suppress*4 OR decreas*4 OR block*3) NEAR10 (Tyrosinase OR melan*8 OR melasma OR chloasma OR suntan OR (solar ADJ2 lentig*) OR pigment*5))) AND ((Bioavailabilit*3 OR (Bio*9 ADJ2 availab*7) OR (Physiologic*2 ADJ2 availab*7) OR (availabilit*3 ADJ2 equivalenc*3)) OR ((Enhanc*4 OR increas*3 OR high*2 OR improv*4 OR promot*3 ) NEAR10 (absor*4 OR permeab*5 OR penetrat*4)))
|align = "center"|54
|-
|align = "center" bgcolor = "#FAC090"|'''8'''
|align = "center"|'''english keywords and japanese f terms for bioavailability'''
|align = "center"|Claims title abstract
|align = "center"|(4C076FF34) OR (4C076FF03) OR (4C076FF32) OR (4C086NA11)
|align = "center"|610
|-
|align = "center" bgcolor = "#FAC090"|'''9'''
|align = "center" colspan = "2"|'''Combined query(Class codes of bio-availability and key words of skin whitening)'''
|align = "center"|6 OR 7 OR 8
|align = "center"|318
|-
|align = "center" bgcolor = "#FAC090"|'''10'''
|align = "center" colspan = "2"|'''Combined query (key word - classcode search)'''
|align = "center"|5 or 9
|align = "center"|6224
|-
|align = "center" bgcolor = "#FAC090"|'''11'''
|align = "center"|'''Skin whitening AND bioavailability key words(English)'''
|align = "center"|Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability
|align = "center"|(((Skin*1 OR*3 derm*2 OR (stratum ADJ2 corneum) OR (stratum lucidum) OR (stratum granulosum) OR (stratum spinosum) OR (stratum basale) OR topical*2) NEAR20 (Whiten*3 OR lighten*3 OR brighten*3 OR fair*4 OR depigment*5)) OR (Skin*1 AND depigment*) OR ((Inhibit*3 OR reduc*4 OR anti OR suppress*4 OR decreas*4 OR block*3) NEAR10 (Tyrosinase OR melan*8 OR melasma OR chloasma OR suntan OR (solar ADJ2 lentig*) OR pigment*5))) AND ((Bioavailabilit*3 OR (Bio*9 ADJ2 availab*7) OR (Physiologic*2 ADJ2 availab*7) OR (availabilit*3 ADJ2 equivalenc*3)) OR ((Enhanc*4 OR increas*3 OR high*2 OR improv*4 OR promot*3 ) NEAR10 (absor*4 OR permeab*5 OR penetrat*4)))
|align = "center"|3820
|-
|align = "center" bgcolor = "#FAC090"|'''12'''
|align = "center"|'''Class codes of bioavailability AND key words of skin whitening(Geman)'''
|align = "center"|Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability
|align = "center"|(((Haut OR pelle OR Häutchen OR dermis OR dermal OR derma OR oberhaut OR epidermis OR epidermalen OR (Schicht ADJ2 corneum) OR (schicht lucidum) OR (stratum granulosum) OR (schicht spinosum) OR (schicht basale) OR aktuelle OR topisch) NEAR20 (bleaching OR machen OR geweißt OR aufhellung OR aufhellen OR aufgehellt OR aufhellung OR aufhellen OR aufgehellt OR messe OR gerechteren OR fairness OR depigmentierung OR depigmented)) OR (Haut*1 AND depigment*) OR ((hemmen OR gehemmt OR hemmung OR reduzieren OR reduktion OR anti OR unterdrücken OR unterdrückt OR Unterdrückung OR Rückgang OR abnehmender OR block OR verstopft OR sperrung) NEAR10 (Tyrosinase OR melan*4 OR melasma OR chloasma OR Pigmentierung OR pigmentierte OR hyperpigmentierungen))) AND (((Bioverfügbarkeit OR bioverfügbarkeiten OR ((Bio OR biologisch OR biologisch) ADJ2 (Verfügbarkeit OR verfügbar))) OR (((physiologisch OR physiologisch) ADJ2 (Verfügbarkeit OR verfügbar)) OR (Verfügbarkeit ADJ2 Gleichwertigkeit))) OR ((Verbesserung OR verbessern OR erhöhen OR erhöht OR erhöht OR erhöhen OR hoch OR verbessern OR verbessert OR Verbesserung OR fördern OR gefördert OR Förderung) NEAR10 (Absorption OR absorbiert OR durchlässig OR Durchlässigkeit OR durchdringen OR Penetration OR eingedrungen)))
|align = "center"|27
|-
|align = "center" bgcolor = "#FAC090"|'''13'''
|align = "center"|'''Class codes of bioavailability AND key words of skin whitening(French)'''
|align = "center"|Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability
|align = "center"|((((la ADJ2 peau) OR peau OR derme OR dermique OR derma OR épiderme OR épidermique OR (strate ADJ2 cornée) OR (strate lucidum) OR (strate granulosum) OR (strate spinosum) OR (strate basale) OR actualité OR topique) NEAR20 (blanchiment OR blanchir OR blanchis OR éclairage OR éclairer OR allégée OR allège OR s<nowiki>’</nowiki>éclaircirs<nowiki>’</nowiki>égayer OR (rendre ADJ2 éclair) OR (faire ADJ2 égayer) OR éclaircissant OR équitables OR foire OR kermesse OR l<nowiki>’</nowiki>équité OR (plus ADJ2 équitable) OR dépigmentation OR dépigmentées)) (peau OR dépigment*) OR (((inhibent OR inhibée OR l<nowiki>’</nowiki>inhibition OR (réduire ADJ2 la) OR (réduction ADJ2 de) OR supprimer OR supprimé OR (la ADJ2 suppression) OR antiparasitage OR baisse OR diminué OR diminue OR décroissante OR bloc OR bloquée OR bloquant)) NEAR10 ((Tyrosinase OR mélanine OR mélanosome OR mélanocyte OR mélanogénèse OR mélasma OR chloasma OR pigments OR pigmentation OR pigmenté)))) AND (((biodisponibilité OR biodisponibilités OR ((Bio OR biologique OR biologiquement) ADJ2 (la disponibilité OR disponibles))) OR (((physiologiques OR physiologiquement) ADJ2 ((la ADJ2 disponibilité) OR disponibles)) OR ((la ADJ2 disponibilité) ADJ2 equivalenc*3))) OR ((amélioration OR améliorer OR (augmentation ADJ2 de) OR augmente OR augmenté OR augmenter OR haute OR hautement OR (améliorer ADJ2 la) OR améliorée OR l<nowiki>’</nowiki>amélioration OR (promouvoir ADJ2 la) OR promu OR (la ADJ2 promotion)) NEAR10 (d<nowiki>’</nowiki>absorption OR absorbés OR perméables OR (la ADJ2 perméabilité) OR pénètrent OR (la ADJ2 pénétration) OR pénétré)))
|align = "center"|14
|-
|align = "center" bgcolor = "#FAC090"|'''14'''
|align = "center" colspan = "2"|'''Combined query (keyword search)'''
|align = "center"|11 OR 12 OR 13
|align = "center"|3856
|-
|align = "center" bgcolor = "#FAC090"|'''15'''
|align = "center" colspan = "2"|'''Combined query (Kewyword search and keyword - Classcode search)'''
|align = "center"|10 OR 14
|align = "center"|9334
|-
|align = "center" bgcolor = "#FAC090"|'''16'''
|align = "center"|'''Key words for irrelevant patents'''
|align = "center"|Title, Abstract
|align = "center"|(Teeth OR tooth OR ink*4 OR paint*3 OR glass*2 OR cement*7)
|align = "center"|2848497
|-
|align = "center" bgcolor = "#FAC090"|'''17'''
|align = "center" colspan = "2"|'''Final query'''
|align = "center"|15 NOT 16
|align = "center"|8391'''(4182 Unique hits)'''
|-
|align = "center" bgcolor = "#FAC090"|'''18'''
|align = "center"|'''L<nowiki>’</nowiki>Oreal'''
|align = "center"|Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment
|align = "center"|"La Institut Lancome" OR "Laboratoires Garnier Paris" OR "Lancome Parfums et Beaute" OR "Paloma Picasso & Cie." OR "Parfums Cachrel & Cie" OR "Parfums et Beaute France & Cie." OR "Parfums Ralph Lauren" OR "Prestige et Collections Inter. & Cie." OR "L<nowiki>’</nowiki>Oreal USA, Inc." OR "L<nowiki>’</nowiki>Oreal USA, Designer Fragrance Division" OR "Soft Sheen/Carson Products, Inc." OR "L<nowiki>’</nowiki>Oreal USA Inc" OR "Beauty Alliance, Inc." OR "Ace Beauty Co." OR "C.B. Sullivan Company Inc." OR "Kiehl<nowiki>’</nowiki>s Since 1851 LLC" OR "Matrix Essentials, Inc." OR "Maybelline, Inc." OR "Maybelline Products Co. Inc." OR "Redken Laboratories LLC" OR "L<nowiki>’</nowiki>Oreal Canada" OR "Parbel Inc." OR "The Body Shop International PLC" OR "A. Christenssen Engros A/S" OR "The Body Shop a Islandi" OR "The Body Shop Beteilgungs-GmbH" OR "The Body Shop (France) SARL" OR "The Body Shop Levy" OR "The Body Shop Oman" OR "The Body Shop Qatar" OR "Body Shop Svenska AB" OR "The Body Shop UK" OR "The Body Shop" OR "BS Denmark A/S" OR "Cosmenatura SA" OR "Dibel Lda" OR "East & Central Al Thomad Co." OR "Ginkgo & Sarantis Romania SA" OR "Koyia Jacovou Speciality Shop Ltd" OR "The Body Shop International Inc." OR "The Body Shop Canada" OR "The Body Shop Singapore (PTE) Ltd." OR "The Body Shop Hong Kong" OR "Bodim Port Oy" OR "L<nowiki>’</nowiki>Oreal Belgilux SA" OR "L<nowiki>’</nowiki>Oreal Parfums" OR "L<nowiki>’</nowiki>Oreal S.A. - Gemey Division" OR "L<nowiki>’</nowiki>Oreal S.A. - Laboratory Division" OR "L<nowiki>’</nowiki>Oreal Japan Ltd." OR "L<nowiki>’</nowiki>Oreal Singapore Pte Ltd" OR "L<nowiki>’</nowiki>Oreal (UK) Limited" OR "L<nowiki>’</nowiki>Oreal Uruguay" OR "Galderma Pharma S.A." OR "Galderma Laboratories, L.P." OR "CollaGenex Pharmaceuticals, Inc." OR "Galderma Brasil Ltda." OR "Galderma Canada, Inc." OR "Galderma International SAS" OR "Galderma Laboratorium GmbH" OR LANCOME* OR GALDERMA* OR "L<nowiki>’</nowiki>Oreal S.A." OR "BIOTHERM" OR "SOCIETEL<nowiki>’</nowiki>OREAL SA" OR "L<nowiki>’</nowiki>OREAL (SA) " OR "LOREAL SA" OR "LOREAL" OR "MAYBELLINE INC" OR "LABORATORIES PHARMACEUTIQUES GOUPIL SA" OR "LANCOME PARFUMES ET BEAUTE & CIE" OR "HELENA RUBINSTEIN SA" OR "SOFT SHEEN PRODUCTS INC" OR "SOREAL SA" OR "LA ROCHE POSAY LABORATOIRE" OR "MAYBELLINE INTERMEDIATE CO" OR "L OREAL" OR "L<nowiki>’</nowiki> OR AL" OR "SOCIETE L<nowiki>’</nowiki> OREAL SA" OR "SOCIETE L<nowiki>’</nowiki>OREAL" OR "SOCIETE L<nowiki>’</nowiki>OREAL SA" OR "SHU UEMURA COSMETICS INC" OR "SHU UEMURA INC" OR "CHIMEX" OR "PARFUMS GUY LAROCHE SA" OR "L<nowiki>’</nowiki>OREAL-D I P I" OR "L<nowiki>’</nowiki>OREAL USA CREATIVE INC" OR "MAYBELLE INC" OR "MAYBELLINE COSMETICS CORP" OR "L <nowiki>’</nowiki>OREAL" OR "HELENA RUBINSTEIN INC" OR "ARTEC SYSTEMS GROUP INC" OR "ROGER & GALLET" OR "L<nowiki>’</nowiki>OREAL S A" OR "L<nowiki>’</nowiki>OREAL USA INC" OR "MAYBELLINE INTERMEDIATE CORP" OR "L<nowiki>’</nowiki> OREAL SA" OR "LABORATOIRES PHARMACEUTIQUES ROCHE-POSAY" OR "LANCOME PARFUMS ET BEAUTIE & CIE" OR "COSMAIR COSMETICS CORP" OR "COSMAIR CREATIVE INC" OR "ARTEC SYSTEMS GROUP" OR "SKINCEUTICALS INC" OR "LA ROCHE POSAY-LABORATOIRE PHARMACEUTIQUE" OR "L<nowiki>’</nowiki>OREAL USA CREATIVE" OR "SOCIETE D<nowiki>’</nowiki>HYGIENE DERMATOLOGIQUE DE VICHY" OR "HELENE RUBENSTEIN INC" OR "L*OREAL" OR "LA ROCHE POSAY LABORATOIRE PHARMACEUTIQUE" OR "L<nowiki>’</nowiki>ORAAL" OR "L<nowiki>’</nowiki>OREAL RENE" OR "L<nowiki>’</nowiki>OREAL USA" OR "L<nowiki>’</nowiki> OREAL" OR "THE BODY SHOP INTERNATIONAL PLC" OR "COSMAIR INC" OR "L<nowiki>’</nowiki>OR(ACUTE OVER (E))AL SA" OR "L<nowiki>’</nowiki>OREAL" OR "L<nowiki>’</nowiki>OREAL S R" OR "L<nowiki>’</nowiki>OREAL SA" OR "L <nowiki>’</nowiki>OREAL SA" OR "LANCOME PARFUMS ET BEAUTE & CIE" OR "YSL BEAUTE" OR "L<nowiki>’</nowiki>OR(ACUTE OVER (E))AL" OR "L<nowiki>’</nowiki>ORA©AL"
|align = "center"|66707
|-
|align = "center" bgcolor = "#FAC090"|'''19'''
|align = "center" colspan = "2"|'''L<nowiki>’</nowiki>Oreal Restricted'''
|align = "center"|17 AND 18
|align = "center"|274('''120 unique hits''')
|-
|align = "center" bgcolor = "#FAC090"|'''20'''
|align = "center"|'''Shiseido'''
|align = "center"|Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment
|align = "center"|"SHISEIDO INTERNATIONAL FRANCE" OR "ZOTOS INTERNATIONAL INC" OR "MIEUX PRODUCTS CO LTD" OR "BEAUTE PRESTIGE INTERNATIONAL SA" OR "SHISEIDO RESEARCH CENTER" OR "AXE CO LTD" OR "ZOTOS INTERNATIONAL" OR "SHISEIDO AMERICAS CORP" OR "BEAUTE PRESTIGE INTERNATIONAL" OR "JOICO LABORATORIES INC" OR "SHISEIDO INTERNATIONAL FRANCE SA" OR "BARE ESCENTUALS INC" OR "SHISEIDO LTD" OR "SHISEIDO CO LTD" OR "CARITA INTERNATIONAL"
|align = "center"|16576
|-
|align = "center" bgcolor = "#FAC090"|'''21'''
|align = "center" colspan = "2"|'''Shiseido Restricted'''
|align = "center"|17 AND 20
|align = "center"|120('''76 unique hits''')
|-
|align = "center" bgcolor = "#FAC090"|'''22'''
|align = "center"|'''Kao and Kanebo'''
|align = "center"|Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment
|align = "center"|"LABTEC GESELLSCAFT FA?R TECHNOLOGISCHE FORSCHUNG UND ENTTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FA?R TECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FA?R TECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FUER TECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FUER TECHOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FUR BIOTECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FUR TECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "NIVEA-KAO CO LTD" OR "NIVEAU AG" OR "TESA AG" OR "TESA AKTEINGESELLSCHAFT" OR "TESA AKTIENGESELLSCHAFT" OR "TESA AKTIENGESELSCHAFT" OR "TESA SCRIBOS GMBH" OR "TESA TAPE INC" OR "TESA TUCK INC" OR "KAO CORP." OR "ANDREW JERGENS CO" OR "GOLDWELL AG" OR "GOLDWELL AKTIENGESELLSCHAFT" OR "GOLDWELL G M B H" OR "GOLDWELL GMBH" OR "HIGH POINT CHEMICAL CORP" OR "KANEBO COSMETICS INC" OR "KAO BRANDS COMAPNY" OR "KAO CHEMICALS EUROPE S L" OR "KAO CHEMICALS GMBH" OR "KAO COPRORATION" OR "KAO CORP" OR "KAO CORP SA" OR "KAO KK" OR "KAO QUAKER CO LTD" OR "KAO SOAP CO LTD" OR "KAO SPECIALTIES AMERICAS" OR "KAO SPECIALTY AMERICAS LLC" OR "KAO KK" OR "KPSS GMBH" OR "KPSS KAO PROFESSIONAL SALON SERVICES GMBH" OR "KPSS-KAO PROFESSIONAL SALON SERVICES GMBH" OR "KPSS-KAO PROFESSISSIONAL SLAON SSERVICES GMBH" OR "MOLTON BROWN USA INC" OR "QUIMIKAO SA DE C V" OR "THE ANDREW JERGENS CO" OR "KAO SUN CHUEH" OR "KANEBO LTD." OR "KANEBO BELL-TOUCH LTD" OR "KANEBO CO LTD" OR "KANEBO GOHSEN LTD" OR "KANEBO GOSEN LTD" OR "KANEBO KK" OR "KANEBO LTD" OR "KANEBO LTD & T HASEGAWA CO LTD" OR "KANEBO RAYON LTD" OR "KANEBO SPINNING CORP" OR "KANEBO SPUN SILK LTD" OR "KANEBO SYNTHETIC FIBERS LTD" OR "KAO CORP." OR "ANDREW JERGENS CO" OR "GOLDWELL AG" OR "GOLDWELL AKTIENGESELLSCHAFT" OR "GOLDWELL G M B H" OR "GOLDWELL GMBH" OR "HIGH POINT CHEMICAL CORP" OR "KANEBO COSMETICS INC" OR "KAO BRANDS COMAPNY" OR "KAO CHEMICALS EUROPE S L" OR "KAO CHEMICALS GMBH" OR "KAO COPRORATION" OR "KAO CORP" OR "KAO CORP SA" OR "KAO KK" OR "KAO KK" OR "KAO QUAKER CO LTD" OR "KAO SOAP CO LTD" OR "KAO SPECIALTIES AMERICAS" OR "KAO SPECIALTY AMERICAS LLC" OR "KOA KK" OR "KPSS GMBH" OR "KPSS KAO PROFESSIONAL SALON SERVICES GMBH" OR "KPSS-KAO PROFESSIONAL SALON SERVICES GMBH" OR "KPSS-KAO PROFESSISSIONAL SLAON SSERVICES GMBH" OR "MOLTON BROWN USA INC" OR "QUIMIKAO SA DE C V" OR "THE ANDREW JERGENS CO" OR "ASSIGNEE NOT STANDARDIZED IN DICTIONARY" OR "KANEBO CHEMICAL INDUSTRIES LTD" OR "KANEBO FOODS LTD" OR "KANEBO LTD /KANTO CHEMICAL CO" OR "KANEBO MICROELECTRONICS LTD" OR "KAO CORPORATION" OR "KAO BRANDS COMPANY"
|align = "center"|94965
|-
|align = "center" bgcolor = "#FAC090"|'''23'''
|align = "center" colspan = "2"|'''Kao and kanebo restricted'''
|align = "center"|17 AND 22
|align = "center"|114('''74 unique hits''')
|}
=Relevant class codes and definitions=
==IPC/ECLA classes==
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FAC090" rowspan = "6"|'''A61'''
|align = "center" bgcolor = "#FAC090" colspan = "3"|Medical or Veterinary science; Hygiene
|-
|align = "center" bgcolor = "#FAC090" rowspan = "2"|'''A61Q'''
|align = "center" bgcolor = "#FAC090" colspan = "2"|Use of cosmetics or similar toilet preparation
|-
|align = "center"|A61Q 19/02
|align = "center"|Preparations for care of the skin =<nowiki>></nowiki>for chemically bleaching or whitening the skin
|-
|}
==US Classes==
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FAC090" rowspan = "4"|'''424'''
|align = "center" bgcolor = "#FAC090" colspan = "2"|Drug, bio-affecting and body treating compositions
|-
|align = "center"|424/62
|align = "center"|Bleach for live hair or skin (e.g., peroxides, etc.)
|-
|align = "center"|424/78.03
|align = "center"|Topical body preparation containing solid synthetic organic polymer as designated organic active ingredient (doai) =<nowiki>></nowiki> Skin cosmetic coating
|-
|align = "center"|424/449
|align = "center"|Transdermal or percutaneous
|-
|align = "center" bgcolor = "#FAC090" rowspan = "6"|'''514'''
|align = "center" bgcolor = "#FAC090" colspan = "2"|Drug, bio-affecting and body treating compositions
|-
|align = "center"|514/1.1
|align = "center"|Designated organic active ingredient containing =<nowiki>></nowiki> Peptide (e.g., protein, etc.) containing DOAI
|-
|align = "center"|514/2.2
|align = "center"|Designated organic active ingredient containing =<nowiki>></nowiki> Peptide (e.g., protein, etc.) containing DOAI=<nowiki>></nowiki> Bactericidal/permeability-increasing (BPI) protein affecting or utilizing
|-
|align = "center"|514/844
|align = "center"|Cosmetic, facial
|-
|align = "center"|514/946
|align = "center"|Penetrant or absorbent (enhances penetration into subject treated)
|-
|align = "center"|514/947
|align = "center"|Penetrant or absorbent (enhances penetration into subject treated) =<nowiki>></nowiki> Topical application
|-
|}
==F-Term==
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FAC090"|'''Theme'''
|align = "center" bgcolor = "#FAC090"|'''Title of the theme'''
|align = "center" bgcolor = "#FAC090"|'''F-term'''
|align = "center" bgcolor = "#FAC090"|'''F-term description'''
|-
|align = "center" bgcolor = "#FAC090"|'''4C083'''
|align = "center"|Cosmetics
|align = "center"|4C083EE16
|align = "center"|Whitening (Tyrosinase inhibition, melanin inhibition)
|-
|align = "center" bgcolor = "#FAC090" rowspan = "3"|'''4C076'''
|align = "center" rowspan = "3"|Medicinal preparation
|align = "center"| 4C076FF34
|align = "center"|Absorption accelerators or penetrants
|-
|align = "center"|4C076FF03
|align = "center"|with absorption, adsorption, or impregnation properties
|-
|align = "center"|4C076FF32
|align = "center"|Biologically absorbed substances
|-
|align = "center" bgcolor = "#FAC090"|'''4C086'''
|align = "center"|Pharmaceuticals containing other organic and inorganic compounds
|align = "center"|4C086NA11
|align = "center"|Absorption improvement
|-
|}
=Clickable taxonomy=
<mm>[[Mmap1290(1.1).mm]]</mm>
=Relevant patents=
[https://dolcera.net/teamwiki_prod/index.php/Relevant_patents Click here to view Relevant patents]
=Analysis=
[[Media:Analysis_final1.xls|'''Click here to download sample analysis sheet''']]
=Trends and Insights=
==Assigneewise preferred skin whitening actives==
[[Image:activesa.jpg|200px|center|frame|thumb|<center>'''Skin-whitening actives vs Assignees'''</center>]]
'''Key Points'''
*Tranexamic acid and derivatives are restricted to Shisheido
*Alpha Hydroxy acid and Tocopherol derivatives are restricted to Loreal
*Vitamin B3 and derivatives are exclusive to P&G
*Loreal exclusively exploits biomolecules such as siRNA and Enzymes in whitening compositions
*P & G uses a novel sodium metabisulfite as skin whitening agent
*Kao and Kanebo prefers natural extract as whitening actives
==Assignee-wise adopted bioavailability enhancing strategies==
[[Image:activesg.jpg|200px|center|frame|thumb|<center>'''Bioavailability enhancing strategies vs Assignees'''</center>]]
'''Key Points'''
*Shiseido prefers chemical compounds as penetration enhancers such as silicone compounds, carboxylic acids, etc.
*L’Oreal’s penetration enhancers are mostly carriers such as liposomes, nanoemulsions, etc. followed by physical methods like iontophoresis, ultrasonic waves etc.
*P & G has a preference for carriers followed by physical methods and chemical compounds
==Preferred solvent with respect to penetration enhancer==
[[Image:activesc.jpg|200px|center|frame|thumb|<center>'''Penetration enhancer (x-axis) vs solvent (z-axis)'''</center>]]
'''Key Points'''
*Vitamins and Salicylic acid derivatives are preferably dissolved in lower alcohols
*Inorganic compounds are used with a wide range of solvents like higher & lower alcohols, acids & derivatives, etc.
*Polyols are used in conjunction with solvents such as glycol, glycerol, lower alcohols and acids
==Delivery strategies for whitening actives==
*The most common skin-whitening agents have been mapped with the usage of penetration enhancer and carrier across the assignees.
*'''Click on the appropriate tab for each active.'''
*'''Each colored cells will give the corresponding information of delivery ingredients/methods'''
{|align = "center"
|<gflash>800 600 http://dolcera.com/upload/files/Dashboard_of_Active_Ingredients.swf</gflash>
|-
|}
=Dashboard=
[https://www.dolcera.com/auth/dashboard_multicategory/dashboard.php?workfile_id=1290 Click here to view the Dashboard ]
A preview of the dashboard is shown below.
[[Image:skreensot.jpg|800px|center|Enhanced bioavailability of skin-whitening ingredients in topical applications]]
To understand different strategies used for enhancing the bioavailability of skin whitening agents in topical applications by various companies.
=Scope=
* This report is restricted to four major players in this technology area- Kao, L'Oreal, P&G and Shiseido.
* We have taken patents as a source of information to understand different methods for enhancing bioavailability.
=Search methodology=
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FCD5B4"|'''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.<br>2.Various Class-codes have been retrieved from relevant patents and their citations. Also . (Refer section 4).<br>3.The database used for patent search is Thomson innovation.
|-
|align = "center" bgcolor = "#FCD5B4"|'''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.[http://www.ncbi.nlm.nih.gov/pubmed/16841367 Parvez et al,2006]
Elimination of melanin can be done in three ways:
*Suppressing Tyrosinase formation
*Inhibiting Tyrosinase activity
*Reduction of Melanin
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.
[[Image:table1.jpg|850px|thumb|center|[http://onlinelibrary.wiley.com/doi/10.1111/j.1468-2494.2010.00616.x/full Gillbro & Olsson,2011]]]
*Because of the accessibility and large area of the skin, it has long been considered as promising route for the administration of drugs, where dermal, regional, or systemic effects are desired. The advantages of the topical route of drug administration include: avoidance of the risks and inconvenience of parenteral treatment; avoidance of the variable absorption and metabolism associated with oral treatment; continuity of drug administration, permitting use of pharmacologically active agents with short biological half-lives and potential reduction of gastrointestinal irritation in systemic administration.[http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN%2F5874095 Deckner et al,1999]
*However, the impermeability of skin is well-known, serving as a barrier to ingress of pathogens and toxic chemicals, and egress of physiologic fluids. This impermeability is the result of normal physiologic changes in developing skin,also results in lesser bioavailability.It is already well known that bioavailability of compounds taken topically example skin whitening ingredients are always lesser than that taken orally or intravenously. Bioavailability of topical dosage forms not intended for absorption has proved to be quite difficult, daunting and extremely challenging.
==Skin whitening ingredients and enhanced bioavailability==
===Bioavailability===
[[Image:Bioavailability.jpg|500px|thumb|right|[http://www.spitalpharmazie-basel.ch/pdf/Diss_Pellanda.pdf Schematic depiction of percutaneous absorption,Pellanda(2006)]]]
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 [http://www.omicsonline.org/0975-0851/JBB-02-102.pdf 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.
*Microemulsion- An oil-in-water microemulsion have the ability to encapsulate non polar molecules such as lipids, flavorants, antimicrobials, antioxidants, and vitamins, it formulated using lecithin and an alkyl glucoside. It was proposed as a cosmetic vehicle for arbutin and kojic acid, naturally occurring whitening agents. The stability of these compounds are higher in microemulsion than in aqueous solutions.[http://www.ncbi.nlm.nih.gov/pubmed/15131725 Gallarate et al,2004]
*Liposomes- Liposomes encapsulate water and lipid-soluble pharmacologically and cosmetically active components. Liposomes favor the disposition of encapsulated active ingredients in the epidermis and dermis, while the permeation rate is decreased. This helps to fix active ingredients to the outermost skin layers as desired for cosmetic products.[http://www.ncbi.nlm.nih.gov/pubmed/15989590 Cevec,1997]
*Nanoemulsions- Nanoemulsions are emulsions having small droplet size (20–300nm). They could be used for lipophilic as well as hydrophilic substances with enhanced bioavailability
[[Image:newer approach2.jpg|850px|thumb|center|[http://www.ncbi.nlm.nih.gov/pubmed/18482010 Chanchal & Swarnalata,2008]]]
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=
[[Click here to view concept table]]
=Search strategy=
*'''Database: Thomson Innovation'''
*'''Coverage:US Grant, GB App, US App, FR App, WO App, DE Util, EP Grant, DE Grant, EP App, DE App, JP Util, JP Grant, JP App, CN Util, CN App, KR Util , KR Grant, KR App, Other, DWPI'''
*'''Time Line:1836 - 19 January 2012'''<br />
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FAC090"|'''S.No'''
|align = "center" bgcolor = "#FAC090"|'''Concept'''
|align = "center" bgcolor = "#FAC090"|'''Scope'''
|align = "center" bgcolor = "#FAC090"|'''Search strategy'''
|align = "center" bgcolor = "#FAC090"|'''Hits'''
|-
|align = "center" bgcolor = "#FAC090"|'''1'''
|align = "center"|'''Class codes of skin whitening AND keywords of bioavailability(English)'''
|align = "center"|Full patent spec.
|align = "center"|(424062) OR (424449) OR (514844) OR (42407803) OR (4C083EE16)OR (A61Q001902) AND ((Bioavailabilit*3 OR (Bio*9 ADJ2 availab*7) OR (Physiologic*2 ADJ2 availab*7) OR (availabilit*3 ADJ2 equivalenc*3)) OR ((Enhanc*4 OR increas*3 OR high*2 OR improv*4 OR promot*3 ) NEAR10 (absor*4 OR permeab*5 OR penetrat*4)))
|align = "center"|5885
|-
|align = "center" bgcolor = "#FAC090"|'''2'''
|align = "center"|'''Class codes of skin whitening AND keywords of bioavailability(German)'''
|align = "center"|Full patent spec.
|align = "center"|(A61Q001902) AND (((Bioverfügbarkeit OR bioverfügbarkeiten OR ((Bio OR biologisch OR biologisch) ADJ2 (Verfügbarkeit OR verfügbar))) OR (((physiologisch OR physiologisch) ADJ2 (Verfügbarkeit OR verfügbar)) OR (Verfügbarkeit ADJ2 Gleichwertigkeit))) OR ((Verbesserung OR verbessern OR erhöhen OR erhöht OR erhöht OR erhöhen OR hoch OR verbessern OR verbessert OR Verbesserung OR fördern OR gefördert OR Förderung) NEAR10 (Absorption OR absorbiert OR durchlässig OR Durchlässigkeit OR durchdringen OR Penetration OR eingedrungen)))
|align = "center"|50
|-
|align = "center" bgcolor = "#FAC090"|'''3'''
|align = "center"|'''Class codes of skin whitening AND keywords of bioavailability(French)'''
|align = "center"|Full patent spec.
|align = "center"|(A61Q001902) AND (((biodisponibilité OR biodisponibilités OR ((Bio OR biologique OR biologiquement) ADJ2 (la disponibilité OR disponibles))) OR (((physiologiques OR physiologiquement) ADJ2 ((la ADJ2 disponibilité) OR disponibles)) OR ((la ADJ2 disponibilité) ADJ2 equivalenc*3))) OR ((amélioration OR améliorer OR (augmentation ADJ2 de) OR augmente OR augmenté OR augmenter OR haute OR hautement OR (améliorer ADJ2 la) OR améliorée OR l<nowiki>’</nowiki>amélioration OR (promouvoir ADJ2 la) OR promu OR (la ADJ2 promotion)) NEAR10 (d<nowiki>’</nowiki>absorption OR absorbés OR perméables OR (la ADJ2 perméabilité) OR pénètrent OR (la ADJ2 pénétration) OR pénétré)))
|align = "center"|105
|-
|align = "center" bgcolor = "#FAC090"|'''4'''
|align = "center"|'''F terms of skin whitening AND keywords of bioavailability (English)'''
|align = "center"|full spec in japanese only
|align = "center"|(4C083EE16) AND ((Bioavailabilit*3 OR (Bio*9 ADJ2 availab*7) OR (Physiologic*2 ADJ2 availab*7) OR (availabilit*3 ADJ2 equivalenc*3)) OR ((Enhanc*4 OR increas*3 OR high*2 OR improv*4 OR promot*3 ) NEAR10 (absor*4 OR permeab*5 OR penetrat*4)))
|align = "center"|445
|-
|align = "center" bgcolor = "#FAC090"|'''5'''
|align = "center" colspan = "2"|'''Combined query (Class code of skin whitening and key words of bioavailability)'''
|align = "center"|1 OR 2 OR 3 or 4
|align = "center"|5973
|-
|align = "center" bgcolor = "#FAC090"|'''6'''
|align = "center"|'''highly relevant class codes of bioavailability and keywords of skin whitening'''
|align = "center"|Claims, Title, Abstract
|align = "center"|((514946) OR (514947) OR (4C076FF34)) AND ((Whiten*3 OR lighten*3 OR brighten*3 OR fair*4 OR depigment*5) OR ((Inhibit*3 OR reduc*4 OR anti OR suppress*4 OR decreas*4 OR block*3) NEAR10 (Tyrosinase OR melan*8 OR melasma OR chloasma OR suntan OR (solar ADJ2 lentig*) OR pigment*5)))
|align = "center"|278
|-
|align = "center" bgcolor = "#FAC090"|'''7'''
|align = "center"|'''Class codes of bioavailability AND key words of skin whitening(English)'''
|align = "center"|Claims title abstract
|align = "center"|(5140011) OR (5140022) OR (514946) OR (514947) AND (((Skin*1 OR*3 derm*2 OR (stratum ADJ2 corneum) OR (stratum lucidum) OR (stratum granulosum) OR (stratum spinosum) OR (stratum basale) OR topical*2) NEAR20 (Whiten*3 OR lighten*3 OR brighten*3 OR fair*4 OR depigment*5)) OR (Skin*1 AND depigment*) OR ((Inhibit*3 OR reduc*4 OR anti OR suppress*4 OR decreas*4 OR block*3) NEAR10 (Tyrosinase OR melan*8 OR melasma OR chloasma OR suntan OR (solar ADJ2 lentig*) OR pigment*5))) AND ((Bioavailabilit*3 OR (Bio*9 ADJ2 availab*7) OR (Physiologic*2 ADJ2 availab*7) OR (availabilit*3 ADJ2 equivalenc*3)) OR ((Enhanc*4 OR increas*3 OR high*2 OR improv*4 OR promot*3 ) NEAR10 (absor*4 OR permeab*5 OR penetrat*4)))
|align = "center"|54
|-
|align = "center" bgcolor = "#FAC090"|'''8'''
|align = "center"|'''english keywords and japanese f terms for bioavailability'''
|align = "center"|Claims title abstract
|align = "center"|(4C076FF34) OR (4C076FF03) OR (4C076FF32) OR (4C086NA11)
|align = "center"|610
|-
|align = "center" bgcolor = "#FAC090"|'''9'''
|align = "center" colspan = "2"|'''Combined query(Class codes of bio-availability and key words of skin whitening)'''
|align = "center"|6 OR 7 OR 8
|align = "center"|318
|-
|align = "center" bgcolor = "#FAC090"|'''10'''
|align = "center" colspan = "2"|'''Combined query (key word - classcode search)'''
|align = "center"|5 or 9
|align = "center"|6224
|-
|align = "center" bgcolor = "#FAC090"|'''11'''
|align = "center"|'''Skin whitening AND bioavailability key words(English)'''
|align = "center"|Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability
|align = "center"|(((Skin*1 OR*3 derm*2 OR (stratum ADJ2 corneum) OR (stratum lucidum) OR (stratum granulosum) OR (stratum spinosum) OR (stratum basale) OR topical*2) NEAR20 (Whiten*3 OR lighten*3 OR brighten*3 OR fair*4 OR depigment*5)) OR (Skin*1 AND depigment*) OR ((Inhibit*3 OR reduc*4 OR anti OR suppress*4 OR decreas*4 OR block*3) NEAR10 (Tyrosinase OR melan*8 OR melasma OR chloasma OR suntan OR (solar ADJ2 lentig*) OR pigment*5))) AND ((Bioavailabilit*3 OR (Bio*9 ADJ2 availab*7) OR (Physiologic*2 ADJ2 availab*7) OR (availabilit*3 ADJ2 equivalenc*3)) OR ((Enhanc*4 OR increas*3 OR high*2 OR improv*4 OR promot*3 ) NEAR10 (absor*4 OR permeab*5 OR penetrat*4)))
|align = "center"|3820
|-
|align = "center" bgcolor = "#FAC090"|'''12'''
|align = "center"|'''Class codes of bioavailability AND key words of skin whitening(Geman)'''
|align = "center"|Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability
|align = "center"|(((Haut OR pelle OR Häutchen OR dermis OR dermal OR derma OR oberhaut OR epidermis OR epidermalen OR (Schicht ADJ2 corneum) OR (schicht lucidum) OR (stratum granulosum) OR (schicht spinosum) OR (schicht basale) OR aktuelle OR topisch) NEAR20 (bleaching OR machen OR geweißt OR aufhellung OR aufhellen OR aufgehellt OR aufhellung OR aufhellen OR aufgehellt OR messe OR gerechteren OR fairness OR depigmentierung OR depigmented)) OR (Haut*1 AND depigment*) OR ((hemmen OR gehemmt OR hemmung OR reduzieren OR reduktion OR anti OR unterdrücken OR unterdrückt OR Unterdrückung OR Rückgang OR abnehmender OR block OR verstopft OR sperrung) NEAR10 (Tyrosinase OR melan*4 OR melasma OR chloasma OR Pigmentierung OR pigmentierte OR hyperpigmentierungen))) AND (((Bioverfügbarkeit OR bioverfügbarkeiten OR ((Bio OR biologisch OR biologisch) ADJ2 (Verfügbarkeit OR verfügbar))) OR (((physiologisch OR physiologisch) ADJ2 (Verfügbarkeit OR verfügbar)) OR (Verfügbarkeit ADJ2 Gleichwertigkeit))) OR ((Verbesserung OR verbessern OR erhöhen OR erhöht OR erhöht OR erhöhen OR hoch OR verbessern OR verbessert OR Verbesserung OR fördern OR gefördert OR Förderung) NEAR10 (Absorption OR absorbiert OR durchlässig OR Durchlässigkeit OR durchdringen OR Penetration OR eingedrungen)))
|align = "center"|27
|-
|align = "center" bgcolor = "#FAC090"|'''13'''
|align = "center"|'''Class codes of bioavailability AND key words of skin whitening(French)'''
|align = "center"|Claims, Title, Abstract for skin whitening AND Full patent spec. for bioavailability
|align = "center"|((((la ADJ2 peau) OR peau OR derme OR dermique OR derma OR épiderme OR épidermique OR (strate ADJ2 cornée) OR (strate lucidum) OR (strate granulosum) OR (strate spinosum) OR (strate basale) OR actualité OR topique) NEAR20 (blanchiment OR blanchir OR blanchis OR éclairage OR éclairer OR allégée OR allège OR s<nowiki>’</nowiki>éclaircirs<nowiki>’</nowiki>égayer OR (rendre ADJ2 éclair) OR (faire ADJ2 égayer) OR éclaircissant OR équitables OR foire OR kermesse OR l<nowiki>’</nowiki>équité OR (plus ADJ2 équitable) OR dépigmentation OR dépigmentées)) (peau OR dépigment*) OR (((inhibent OR inhibée OR l<nowiki>’</nowiki>inhibition OR (réduire ADJ2 la) OR (réduction ADJ2 de) OR supprimer OR supprimé OR (la ADJ2 suppression) OR antiparasitage OR baisse OR diminué OR diminue OR décroissante OR bloc OR bloquée OR bloquant)) NEAR10 ((Tyrosinase OR mélanine OR mélanosome OR mélanocyte OR mélanogénèse OR mélasma OR chloasma OR pigments OR pigmentation OR pigmenté)))) AND (((biodisponibilité OR biodisponibilités OR ((Bio OR biologique OR biologiquement) ADJ2 (la disponibilité OR disponibles))) OR (((physiologiques OR physiologiquement) ADJ2 ((la ADJ2 disponibilité) OR disponibles)) OR ((la ADJ2 disponibilité) ADJ2 equivalenc*3))) OR ((amélioration OR améliorer OR (augmentation ADJ2 de) OR augmente OR augmenté OR augmenter OR haute OR hautement OR (améliorer ADJ2 la) OR améliorée OR l<nowiki>’</nowiki>amélioration OR (promouvoir ADJ2 la) OR promu OR (la ADJ2 promotion)) NEAR10 (d<nowiki>’</nowiki>absorption OR absorbés OR perméables OR (la ADJ2 perméabilité) OR pénètrent OR (la ADJ2 pénétration) OR pénétré)))
|align = "center"|14
|-
|align = "center" bgcolor = "#FAC090"|'''14'''
|align = "center" colspan = "2"|'''Combined query (keyword search)'''
|align = "center"|11 OR 12 OR 13
|align = "center"|3856
|-
|align = "center" bgcolor = "#FAC090"|'''15'''
|align = "center" colspan = "2"|'''Combined query (Kewyword search and keyword - Classcode search)'''
|align = "center"|10 OR 14
|align = "center"|9334
|-
|align = "center" bgcolor = "#FAC090"|'''16'''
|align = "center"|'''Key words for irrelevant patents'''
|align = "center"|Title, Abstract
|align = "center"|(Teeth OR tooth OR ink*4 OR paint*3 OR glass*2 OR cement*7)
|align = "center"|2848497
|-
|align = "center" bgcolor = "#FAC090"|'''17'''
|align = "center" colspan = "2"|'''Final query'''
|align = "center"|15 NOT 16
|align = "center"|8391'''(4182 Unique hits)'''
|-
|align = "center" bgcolor = "#FAC090"|'''18'''
|align = "center"|'''L<nowiki>’</nowiki>Oreal'''
|align = "center"|Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment
|align = "center"|"La Institut Lancome" OR "Laboratoires Garnier Paris" OR "Lancome Parfums et Beaute" OR "Paloma Picasso & Cie." OR "Parfums Cachrel & Cie" OR "Parfums et Beaute France & Cie." OR "Parfums Ralph Lauren" OR "Prestige et Collections Inter. & Cie." OR "L<nowiki>’</nowiki>Oreal USA, Inc." OR "L<nowiki>’</nowiki>Oreal USA, Designer Fragrance Division" OR "Soft Sheen/Carson Products, Inc." OR "L<nowiki>’</nowiki>Oreal USA Inc" OR "Beauty Alliance, Inc." OR "Ace Beauty Co." OR "C.B. Sullivan Company Inc." OR "Kiehl<nowiki>’</nowiki>s Since 1851 LLC" OR "Matrix Essentials, Inc." OR "Maybelline, Inc." OR "Maybelline Products Co. Inc." OR "Redken Laboratories LLC" OR "L<nowiki>’</nowiki>Oreal Canada" OR "Parbel Inc." OR "The Body Shop International PLC" OR "A. Christenssen Engros A/S" OR "The Body Shop a Islandi" OR "The Body Shop Beteilgungs-GmbH" OR "The Body Shop (France) SARL" OR "The Body Shop Levy" OR "The Body Shop Oman" OR "The Body Shop Qatar" OR "Body Shop Svenska AB" OR "The Body Shop UK" OR "The Body Shop" OR "BS Denmark A/S" OR "Cosmenatura SA" OR "Dibel Lda" OR "East & Central Al Thomad Co." OR "Ginkgo & Sarantis Romania SA" OR "Koyia Jacovou Speciality Shop Ltd" OR "The Body Shop International Inc." OR "The Body Shop Canada" OR "The Body Shop Singapore (PTE) Ltd." OR "The Body Shop Hong Kong" OR "Bodim Port Oy" OR "L<nowiki>’</nowiki>Oreal Belgilux SA" OR "L<nowiki>’</nowiki>Oreal Parfums" OR "L<nowiki>’</nowiki>Oreal S.A. - Gemey Division" OR "L<nowiki>’</nowiki>Oreal S.A. - Laboratory Division" OR "L<nowiki>’</nowiki>Oreal Japan Ltd." OR "L<nowiki>’</nowiki>Oreal Singapore Pte Ltd" OR "L<nowiki>’</nowiki>Oreal (UK) Limited" OR "L<nowiki>’</nowiki>Oreal Uruguay" OR "Galderma Pharma S.A." OR "Galderma Laboratories, L.P." OR "CollaGenex Pharmaceuticals, Inc." OR "Galderma Brasil Ltda." OR "Galderma Canada, Inc." OR "Galderma International SAS" OR "Galderma Laboratorium GmbH" OR LANCOME* OR GALDERMA* OR "L<nowiki>’</nowiki>Oreal S.A." OR "BIOTHERM" OR "SOCIETEL<nowiki>’</nowiki>OREAL SA" OR "L<nowiki>’</nowiki>OREAL (SA) " OR "LOREAL SA" OR "LOREAL" OR "MAYBELLINE INC" OR "LABORATORIES PHARMACEUTIQUES GOUPIL SA" OR "LANCOME PARFUMES ET BEAUTE & CIE" OR "HELENA RUBINSTEIN SA" OR "SOFT SHEEN PRODUCTS INC" OR "SOREAL SA" OR "LA ROCHE POSAY LABORATOIRE" OR "MAYBELLINE INTERMEDIATE CO" OR "L OREAL" OR "L<nowiki>’</nowiki> OR AL" OR "SOCIETE L<nowiki>’</nowiki> OREAL SA" OR "SOCIETE L<nowiki>’</nowiki>OREAL" OR "SOCIETE L<nowiki>’</nowiki>OREAL SA" OR "SHU UEMURA COSMETICS INC" OR "SHU UEMURA INC" OR "CHIMEX" OR "PARFUMS GUY LAROCHE SA" OR "L<nowiki>’</nowiki>OREAL-D I P I" OR "L<nowiki>’</nowiki>OREAL USA CREATIVE INC" OR "MAYBELLE INC" OR "MAYBELLINE COSMETICS CORP" OR "L <nowiki>’</nowiki>OREAL" OR "HELENA RUBINSTEIN INC" OR "ARTEC SYSTEMS GROUP INC" OR "ROGER & GALLET" OR "L<nowiki>’</nowiki>OREAL S A" OR "L<nowiki>’</nowiki>OREAL USA INC" OR "MAYBELLINE INTERMEDIATE CORP" OR "L<nowiki>’</nowiki> OREAL SA" OR "LABORATOIRES PHARMACEUTIQUES ROCHE-POSAY" OR "LANCOME PARFUMS ET BEAUTIE & CIE" OR "COSMAIR COSMETICS CORP" OR "COSMAIR CREATIVE INC" OR "ARTEC SYSTEMS GROUP" OR "SKINCEUTICALS INC" OR "LA ROCHE POSAY-LABORATOIRE PHARMACEUTIQUE" OR "L<nowiki>’</nowiki>OREAL USA CREATIVE" OR "SOCIETE D<nowiki>’</nowiki>HYGIENE DERMATOLOGIQUE DE VICHY" OR "HELENE RUBENSTEIN INC" OR "L*OREAL" OR "LA ROCHE POSAY LABORATOIRE PHARMACEUTIQUE" OR "L<nowiki>’</nowiki>ORAAL" OR "L<nowiki>’</nowiki>OREAL RENE" OR "L<nowiki>’</nowiki>OREAL USA" OR "L<nowiki>’</nowiki> OREAL" OR "THE BODY SHOP INTERNATIONAL PLC" OR "COSMAIR INC" OR "L<nowiki>’</nowiki>OR(ACUTE OVER (E))AL SA" OR "L<nowiki>’</nowiki>OREAL" OR "L<nowiki>’</nowiki>OREAL S R" OR "L<nowiki>’</nowiki>OREAL SA" OR "L <nowiki>’</nowiki>OREAL SA" OR "LANCOME PARFUMS ET BEAUTE & CIE" OR "YSL BEAUTE" OR "L<nowiki>’</nowiki>OR(ACUTE OVER (E))AL" OR "L<nowiki>’</nowiki>ORA©AL"
|align = "center"|66707
|-
|align = "center" bgcolor = "#FAC090"|'''19'''
|align = "center" colspan = "2"|'''L<nowiki>’</nowiki>Oreal Restricted'''
|align = "center"|17 AND 18
|align = "center"|274('''120 unique hits''')
|-
|align = "center" bgcolor = "#FAC090"|'''20'''
|align = "center"|'''Shiseido'''
|align = "center"|Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment
|align = "center"|"SHISEIDO INTERNATIONAL FRANCE" OR "ZOTOS INTERNATIONAL INC" OR "MIEUX PRODUCTS CO LTD" OR "BEAUTE PRESTIGE INTERNATIONAL SA" OR "SHISEIDO RESEARCH CENTER" OR "AXE CO LTD" OR "ZOTOS INTERNATIONAL" OR "SHISEIDO AMERICAS CORP" OR "BEAUTE PRESTIGE INTERNATIONAL" OR "JOICO LABORATORIES INC" OR "SHISEIDO INTERNATIONAL FRANCE SA" OR "BARE ESCENTUALS INC" OR "SHISEIDO LTD" OR "SHISEIDO CO LTD" OR "CARITA INTERNATIONAL"
|align = "center"|16576
|-
|align = "center" bgcolor = "#FAC090"|'''21'''
|align = "center" colspan = "2"|'''Shiseido Restricted'''
|align = "center"|17 AND 20
|align = "center"|120('''76 unique hits''')
|-
|align = "center" bgcolor = "#FAC090"|'''22'''
|align = "center"|'''Kao and Kanebo'''
|align = "center"|Assignee Applicant, Assignee/Applicant Standardized, Assignee/ applicant original, Assignee Applicant DWPI and US reassignment
|align = "center"|"LABTEC GESELLSCAFT FA?R TECHNOLOGISCHE FORSCHUNG UND ENTTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FA?R TECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FA?R TECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FUER TECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FUER TECHOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FUR BIOTECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "LABTEC GESELLSCHAFT FUR TECHNOLOGISCHE FORSCHUNG UND ENTWICKLUNG MBH" OR "NIVEA-KAO CO LTD" OR "NIVEAU AG" OR "TESA AG" OR "TESA AKTEINGESELLSCHAFT" OR "TESA AKTIENGESELLSCHAFT" OR "TESA AKTIENGESELSCHAFT" OR "TESA SCRIBOS GMBH" OR "TESA TAPE INC" OR "TESA TUCK INC" OR "KAO CORP." OR "ANDREW JERGENS CO" OR "GOLDWELL AG" OR "GOLDWELL AKTIENGESELLSCHAFT" OR "GOLDWELL G M B H" OR "GOLDWELL GMBH" OR "HIGH POINT CHEMICAL CORP" OR "KANEBO COSMETICS INC" OR "KAO BRANDS COMAPNY" OR "KAO CHEMICALS EUROPE S L" OR "KAO CHEMICALS GMBH" OR "KAO COPRORATION" OR "KAO CORP" OR "KAO CORP SA" OR "KAO KK" OR "KAO QUAKER CO LTD" OR "KAO SOAP CO LTD" OR "KAO SPECIALTIES AMERICAS" OR "KAO SPECIALTY AMERICAS LLC" OR "KAO KK" OR "KPSS GMBH" OR "KPSS KAO PROFESSIONAL SALON SERVICES GMBH" OR "KPSS-KAO PROFESSIONAL SALON SERVICES GMBH" OR "KPSS-KAO PROFESSISSIONAL SLAON SSERVICES GMBH" OR "MOLTON BROWN USA INC" OR "QUIMIKAO SA DE C V" OR "THE ANDREW JERGENS CO" OR "KAO SUN CHUEH" OR "KANEBO LTD." OR "KANEBO BELL-TOUCH LTD" OR "KANEBO CO LTD" OR "KANEBO GOHSEN LTD" OR "KANEBO GOSEN LTD" OR "KANEBO KK" OR "KANEBO LTD" OR "KANEBO LTD & T HASEGAWA CO LTD" OR "KANEBO RAYON LTD" OR "KANEBO SPINNING CORP" OR "KANEBO SPUN SILK LTD" OR "KANEBO SYNTHETIC FIBERS LTD" OR "KAO CORP." OR "ANDREW JERGENS CO" OR "GOLDWELL AG" OR "GOLDWELL AKTIENGESELLSCHAFT" OR "GOLDWELL G M B H" OR "GOLDWELL GMBH" OR "HIGH POINT CHEMICAL CORP" OR "KANEBO COSMETICS INC" OR "KAO BRANDS COMAPNY" OR "KAO CHEMICALS EUROPE S L" OR "KAO CHEMICALS GMBH" OR "KAO COPRORATION" OR "KAO CORP" OR "KAO CORP SA" OR "KAO KK" OR "KAO KK" OR "KAO QUAKER CO LTD" OR "KAO SOAP CO LTD" OR "KAO SPECIALTIES AMERICAS" OR "KAO SPECIALTY AMERICAS LLC" OR "KOA KK" OR "KPSS GMBH" OR "KPSS KAO PROFESSIONAL SALON SERVICES GMBH" OR "KPSS-KAO PROFESSIONAL SALON SERVICES GMBH" OR "KPSS-KAO PROFESSISSIONAL SLAON SSERVICES GMBH" OR "MOLTON BROWN USA INC" OR "QUIMIKAO SA DE C V" OR "THE ANDREW JERGENS CO" OR "ASSIGNEE NOT STANDARDIZED IN DICTIONARY" OR "KANEBO CHEMICAL INDUSTRIES LTD" OR "KANEBO FOODS LTD" OR "KANEBO LTD /KANTO CHEMICAL CO" OR "KANEBO MICROELECTRONICS LTD" OR "KAO CORPORATION" OR "KAO BRANDS COMPANY"
|align = "center"|94965
|-
|align = "center" bgcolor = "#FAC090"|'''23'''
|align = "center" colspan = "2"|'''Kao and kanebo restricted'''
|align = "center"|17 AND 22
|align = "center"|114('''74 unique hits''')
|}
=Relevant class codes and definitions=
==IPC/ECLA classes==
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FAC090" rowspan = "6"|'''A61'''
|align = "center" bgcolor = "#FAC090" colspan = "3"|Medical or Veterinary science; Hygiene
|-
|align = "center" bgcolor = "#FAC090" rowspan = "2"|'''A61Q'''
|align = "center" bgcolor = "#FAC090" colspan = "2"|Use of cosmetics or similar toilet preparation
|-
|align = "center"|A61Q 19/02
|align = "center"|Preparations for care of the skin =<nowiki>></nowiki>for chemically bleaching or whitening the skin
|-
|}
==US Classes==
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FAC090" rowspan = "4"|'''424'''
|align = "center" bgcolor = "#FAC090" colspan = "2"|Drug, bio-affecting and body treating compositions
|-
|align = "center"|424/62
|align = "center"|Bleach for live hair or skin (e.g., peroxides, etc.)
|-
|align = "center"|424/78.03
|align = "center"|Topical body preparation containing solid synthetic organic polymer as designated organic active ingredient (doai) =<nowiki>></nowiki> Skin cosmetic coating
|-
|align = "center"|424/449
|align = "center"|Transdermal or percutaneous
|-
|align = "center" bgcolor = "#FAC090" rowspan = "6"|'''514'''
|align = "center" bgcolor = "#FAC090" colspan = "2"|Drug, bio-affecting and body treating compositions
|-
|align = "center"|514/1.1
|align = "center"|Designated organic active ingredient containing =<nowiki>></nowiki> Peptide (e.g., protein, etc.) containing DOAI
|-
|align = "center"|514/2.2
|align = "center"|Designated organic active ingredient containing =<nowiki>></nowiki> Peptide (e.g., protein, etc.) containing DOAI=<nowiki>></nowiki> Bactericidal/permeability-increasing (BPI) protein affecting or utilizing
|-
|align = "center"|514/844
|align = "center"|Cosmetic, facial
|-
|align = "center"|514/946
|align = "center"|Penetrant or absorbent (enhances penetration into subject treated)
|-
|align = "center"|514/947
|align = "center"|Penetrant or absorbent (enhances penetration into subject treated) =<nowiki>></nowiki> Topical application
|-
|}
==F-Term==
{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FAC090"|'''Theme'''
|align = "center" bgcolor = "#FAC090"|'''Title of the theme'''
|align = "center" bgcolor = "#FAC090"|'''F-term'''
|align = "center" bgcolor = "#FAC090"|'''F-term description'''
|-
|align = "center" bgcolor = "#FAC090"|'''4C083'''
|align = "center"|Cosmetics
|align = "center"|4C083EE16
|align = "center"|Whitening (Tyrosinase inhibition, melanin inhibition)
|-
|align = "center" bgcolor = "#FAC090" rowspan = "3"|'''4C076'''
|align = "center" rowspan = "3"|Medicinal preparation
|align = "center"| 4C076FF34
|align = "center"|Absorption accelerators or penetrants
|-
|align = "center"|4C076FF03
|align = "center"|with absorption, adsorption, or impregnation properties
|-
|align = "center"|4C076FF32
|align = "center"|Biologically absorbed substances
|-
|align = "center" bgcolor = "#FAC090"|'''4C086'''
|align = "center"|Pharmaceuticals containing other organic and inorganic compounds
|align = "center"|4C086NA11
|align = "center"|Absorption improvement
|-
|}
=Clickable taxonomy=
<mm>[[Mmap1290(1.1).mm]]</mm>
=Relevant patents=
[https://dolcera.net/teamwiki_prod/index.php/Relevant_patents Click here to view Relevant patents]
=Analysis=
[[Media:Analysis_final1.xls|'''Click here to download sample analysis sheet''']]
=Trends and Insights=
==Assigneewise preferred skin whitening actives==
[[Image:activesa.jpg|200px|center|frame|thumb|<center>'''Skin-whitening actives vs Assignees'''</center>]]
'''Key Points'''
*Tranexamic acid and derivatives are restricted to Shisheido
*Alpha Hydroxy acid and Tocopherol derivatives are restricted to Loreal
*Vitamin B3 and derivatives are exclusive to P&G
*Loreal exclusively exploits biomolecules such as siRNA and Enzymes in whitening compositions
*P & G uses a novel sodium metabisulfite as skin whitening agent
*Kao and Kanebo prefers natural extract as whitening actives
==Assignee-wise adopted bioavailability enhancing strategies==
[[Image:activesg.jpg|200px|center|frame|thumb|<center>'''Bioavailability enhancing strategies vs Assignees'''</center>]]
'''Key Points'''
*Shiseido prefers chemical compounds as penetration enhancers such as silicone compounds, carboxylic acids, etc.
*L’Oreal’s penetration enhancers are mostly carriers such as liposomes, nanoemulsions, etc. followed by physical methods like iontophoresis, ultrasonic waves etc.
*P & G has a preference for carriers followed by physical methods and chemical compounds
==Preferred solvent with respect to penetration enhancer==
[[Image:activesc.jpg|200px|center|frame|thumb|<center>'''Penetration enhancer (x-axis) vs solvent (z-axis)'''</center>]]
'''Key Points'''
*Vitamins and Salicylic acid derivatives are preferably dissolved in lower alcohols
*Inorganic compounds are used with a wide range of solvents like higher & lower alcohols, acids & derivatives, etc.
*Polyols are used in conjunction with solvents such as glycol, glycerol, lower alcohols and acids
==Delivery strategies for whitening actives==
*The most common skin-whitening agents have been mapped with the usage of penetration enhancer and carrier across the assignees.
*'''Click on the appropriate tab for each active.'''
*'''Each colored cells will give the corresponding information of delivery ingredients/methods'''
{|align = "center"
|<gflash>800 600 http://dolcera.com/upload/files/Dashboard_of_Active_Ingredients.swf</gflash>
|-
|}
=Dashboard=
[https://www.dolcera.com/auth/dashboard_multicategory/dashboard.php?workfile_id=1290 Click here to view the Dashboard ]
A preview of the dashboard is shown below.
[[Image:skreensot.jpg|800px|center|Enhanced bioavailability of skin-whitening ingredients in topical applications]]
