DE68912923D1 - Penetrationsfördernde oxazolidinonverbindungen. - Google Patents

Penetrationsfördernde oxazolidinonverbindungen.

Info

Publication number
DE68912923D1
DE68912923D1 DE89908033T DE68912923T DE68912923D1 DE 68912923 D1 DE68912923 D1 DE 68912923D1 DE 89908033 T DE89908033 T DE 89908033T DE 68912923 T DE68912923 T DE 68912923T DE 68912923 D1 DE68912923 D1 DE 68912923D1
Authority
DE
Germany
Prior art keywords
penetration
promoting
oxazolidinone compounds
oxazolidinone
compounds
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
DE89908033T
Other languages
English (en)
Other versions
DE68912923T2 (de
Inventor
Vithal J Rajadhyaksha
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of DE68912923D1 publication Critical patent/DE68912923D1/de
Application granted granted Critical
Publication of DE68912923T2 publication Critical patent/DE68912923T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/24—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms
    • A01N43/26—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/86—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/02—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings containing insect repellants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
DE68912923T 1988-07-12 1989-06-23 Penetrationsfördernde oxazolidinonverbindungen. Expired - Fee Related DE68912923T2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US07/218,316 US4960771A (en) 1988-07-12 1988-07-12 Oxazolidinone penetration enhancing compounds
PCT/US1989/002779 WO1990000407A1 (en) 1988-07-12 1989-06-23 Oxazolidinone penetration enhancing compounds

Publications (2)

Publication Number Publication Date
DE68912923D1 true DE68912923D1 (de) 1994-03-17
DE68912923T2 DE68912923T2 (de) 1994-07-28

Family

ID=22814618

Family Applications (1)

Application Number Title Priority Date Filing Date
DE68912923T Expired - Fee Related DE68912923T2 (de) 1988-07-12 1989-06-23 Penetrationsfördernde oxazolidinonverbindungen.

Country Status (5)

Country Link
US (1) US4960771A (de)
EP (1) EP0378657B1 (de)
JP (1) JP2901297B2 (de)
DE (1) DE68912923T2 (de)
WO (1) WO1990000407A1 (de)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4876249A (en) * 1987-01-12 1989-10-24 Rajadhyaksha Vithal J Compositions and method comprising heterocyclic compounds containing two heteroatoms
US5234959A (en) * 1988-04-08 1993-08-10 Whitby Research, Inc. Penetration enhancers for transdermal delivery of systemic agents
US5472946A (en) * 1988-04-08 1995-12-05 Peck; James V. Transdermal penetration enhancers
US5156666A (en) * 1989-12-11 1992-10-20 Isp Investments Inc. Delivery system for agricultural chemicals
US6086905A (en) * 1991-03-21 2000-07-11 Peck; James V. Topical compositions useful as skin penetration barriers
US5414014A (en) * 1993-04-08 1995-05-09 Innova Biomed, Inc. Methods for efficacious removal of attached, sucking antropods from human dermis
CN1115576A (zh) * 1993-10-15 1996-01-24 盐野义制药株式会社 具有细胞浆磷脂酶a2抑制活性的噁唑啉酮衍生物
DE4443888A1 (de) * 1994-12-09 1996-06-13 Bayer Ag Dermal applizierbare Formulierungen von Parasitiziden
US5575988A (en) * 1995-04-07 1996-11-19 Littlepoint Corp. Combination sunscreen and insect repellent
JP2001518057A (ja) * 1995-07-07 2001-10-09 ダーハム ファーマシューティカルズ，エルエルシー 環状アミドおよびそれらの誘導体
ZA966885B (en) * 1995-08-22 1998-02-16 Du Pont Merck Pharma Substituted cyclic ureas and derivatives thereof useful as retroviral protease inhibitors.
DE19613334A1 (de) * 1996-04-03 1997-10-09 Bayer Ag Mittel zur Bekämpfung parasitierender Insekten und Milben an Menschen
FR2754449B1 (fr) * 1996-10-14 1998-11-13 Oreal Utilisation de derives d'oxazolidinone comme agents anti-penetrants dans une composition cosmetique et/ou dermatologique
US20060002949A1 (en) 1996-11-14 2006-01-05 Army Govt. Of The Usa, As Rep. By Secretary Of The Office Of The Command Judge Advocate, Hq Usamrmc. Transcutaneous immunization without heterologous adjuvant
US6797276B1 (en) 1996-11-14 2004-09-28 The United States Of America As Represented By The Secretary Of The Army Use of penetration enhancers and barrier disruption agents to enhance the transcutaneous immune response
US5980898A (en) 1996-11-14 1999-11-09 The United States Of America As Represented By The U.S. Army Medical Research & Material Command Adjuvant for transcutaneous immunization
MY122454A (en) * 1998-06-05 2006-04-29 Upjohn Co Use of oxazolidinones for the preparation of a medicament for transdermal delivery
JP4803511B2 (ja) * 2000-08-25 2011-10-26 株式会社ポーラファルマ 抗真菌医薬組成物
DE60227157D1 (de) 2001-02-13 2008-07-31 Us Gov Sec Army Impstoffe zur transkutanen immunisierung gegen reisediarrhö
JP2003012468A (ja) * 2001-06-28 2003-01-15 Kaminomoto Co Ltd 養毛・発毛促進剤
US6537985B1 (en) * 2001-11-30 2003-03-25 Phoenix Scientific, Inc. Antibiotic formulation and a method of making this formulation
US20040033253A1 (en) * 2002-02-19 2004-02-19 Ihor Shevchuk Acyl opioid antagonists
US20040033255A1 (en) 2002-06-10 2004-02-19 Baker Carl J. Transdermal delivery device disposal system
ATE423560T1 (de) * 2002-08-20 2009-03-15 Euro Celtique Sa Transdermale dosierungsform enthaltend einen wirkstoff und einen antagonisten in freier base und in salz form
FR2847473B1 (fr) * 2002-11-25 2007-06-29 Expanscience Lab Composition comprenant au moins une oxazolidinone, son utilisation cosmetique et comme medicament
US7053085B2 (en) * 2003-03-26 2006-05-30 Merck & Co. Inc. EP4 receptor agonist, compositions and methods thereof
US20080020028A1 (en) * 2003-08-20 2008-01-24 Euro-Celtique S.A. Transdermal dosage form comprising an active agent and a salt and a free-base form of an adverse agent
US7666914B2 (en) * 2004-06-03 2010-02-23 Richlin David M Topical preparation and method for transdermal delivery and localization of therapeutic agents
WO2007100047A1 (ja) * 2006-03-02 2007-09-07 Ube Industries, Ltd. ２－イミダゾリジノン化合物及び４，５－ジアルコキシ－２－イミダゾリジノン化合物の製造方法
FR2908653B1 (fr) * 2006-11-16 2012-08-03 Lvmh Rech Utilisation d'une alkyloxazolidinone comme agent cosmetique hydratant et procede d'hydratation de la peau
FR2908650B1 (fr) * 2006-11-16 2012-05-25 Lvmh Rech Utilisation d'une alkyloxazolidinone comme agent cosmetique hydratant et procede d'hydratation de la peau.
IL181217A0 (en) * 2007-02-08 2007-07-04 Haim Levy Pharmaceuticalcompositions based on a microemulsion
EP2033957A1 (de) * 2007-09-06 2009-03-11 SOLVAY (Société Anonyme) Verfahren zur Herstellung von Alkylverbindungen
EP2484359B1 (de) 2009-09-30 2018-07-25 Shiseido Company, Ltd. Heparanaseaktivitätshemmer
FR2950807B1 (fr) 2009-10-06 2012-02-03 Lvmh Rech Composition cosmetique contenant des liposomes encapsules dans un compose oxazolidin-2-one
CN105828787B (zh) 2013-12-19 2019-07-26 宝洁公司 使用氧代乙酸和/或它们的衍生物使角蛋白纤维成形
WO2015094759A1 (en) 2013-12-19 2015-06-25 The Procter & Gamble Company Shaping keratin fibres using an active agent comprising at least two functional groups selected from: -c(oh)- and -c(=o)oh
MX2016007998A (es) 2013-12-19 2016-09-13 Procter & Gamble Modelado de fibras de queratina mediante el uso de ester de carbonato.
WO2015094838A1 (en) 2013-12-19 2015-06-25 The Procter & Gamble Company Shaping keratin fibres using a reducing composition and a fixing composition
JP6314234B2 (ja) 2013-12-19 2018-04-18 ザ プロクター アンド ギャンブル カンパニー ２−ヒドロキシプロパン−１，２，３−トリカルボン酸及び／又は１，２，３，４−ブタンテトラカルボン酸を使用したヒトの毛髪をまっすぐにする方法
CN105828786B (zh) 2013-12-19 2020-07-07 宝洁公司 使用包含选自-c(＝o)-、-c(＝o)-h和-c(＝o)-o-的官能团的an活性剂使角蛋白纤维成形
JP6385438B2 (ja) 2013-12-19 2018-09-05 ザ プロクター アンド ギャンブル カンパニー 糖類を使用したケラチン繊維の成形
WO2016100257A1 (en) 2014-12-19 2016-06-23 The Procter & Gamble Company Shaping keratin fibres using arabinose and ethylene carbonate
WO2016100258A1 (en) 2014-12-19 2016-06-23 The Procter & Gamble Company Method of shaping keratin fibres
EP3310325A1 (de) 2015-06-18 2018-04-25 The Procter and Gamble Company Formung von keratinfasern mit dialdehydverbindungen
JP6615916B2 (ja) * 2015-06-18 2019-12-04 ザ プロクター アンド ギャンブル カンパニー ２−オキサゾリジノン化合物を使用したケラチン繊維の整形

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2909467A (en) * 1958-07-09 1959-10-20 Us Vitamin Pharm Corp 3-(d-alpha-methylphenethyl)-5-methyl-1, 3-oxazolidine-2, 4-dione
US4405616A (en) * 1975-06-19 1983-09-20 Nelson Research & Development Company Penetration enhancers for transdermal drug delivery of systemic agents
DE2614723C2 (de) * 1976-04-06 1986-01-02 Wella Ag, 6100 Darmstadt Kosmetisches Mittel
DE2704904A1 (de) * 1977-02-05 1978-08-10 Henkel Kgaa Kosmetische mittel mit einem gehalt an haut-feuchthaltemitteln
DE2746650A1 (de) * 1977-10-17 1979-04-26 Henkel Kgaa Kosmetische mittel mit einem gehalt an haut-feuchthaltemitteln
US4279901A (en) * 1979-12-31 1981-07-21 American Cyanamid Company Topical ointment
US4423040A (en) * 1980-04-04 1983-12-27 Nelson Research & Development Company Vehicle composition containing 1-substituted azacyclohexan-2-ones
US4594243A (en) * 1984-07-25 1986-06-10 Nitto Electric Industrial Co., Ltd. Base composition for medicament and pharmaceutical composition for external medication
US4677131A (en) * 1985-11-01 1987-06-30 Merck & Co., Inc. Cyclic ureas as dermal penetration enhancers

Also Published As

Publication number Publication date
WO1990000407A1 (en) 1990-01-25
US4960771A (en) 1990-10-02
JPH03500298A (ja) 1991-01-24
EP0378657A1 (de) 1990-07-25
EP0378657B1 (de) 1994-02-02
JP2901297B2 (ja) 1999-06-07
DE68912923T2 (de) 1994-07-28

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Legal Events

Date Code Title Description
8380 Miscellaneous part iii

Free format text: DER INHABER IST ZU AENDERN IN: THERAPEUTIC PATCH RESEARCH N.V., NEW YORK, NEW YORK, US

8381 Inventor (new situation)

Free format text: RAJADHYAKSHA, VITHAL J., ARLINGTON, TEXAS 76017, US

8364 No opposition during term of opposition
8339 Ceased/non-payment of the annual fee