WO1988008295A1 - Hair growth inhibition using substitued amidines or guanidines - Google Patents

Hair growth inhibition using substitued amidines or guanidines Download PDF

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Publication number
WO1988008295A1
WO1988008295A1 PCT/US1988/000400 US8800400W WO8808295A1 WO 1988008295 A1 WO1988008295 A1 WO 1988008295A1 US 8800400 W US8800400 W US 8800400W WO 8808295 A1 WO8808295 A1 WO 8808295A1
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WO
WIPO (PCT)
Prior art keywords
adamantyl
morpholinecarboxamidine
cyclohexyl
compound
growth
Prior art date
Application number
PCT/US1988/000400
Other languages
French (fr)
Inventor
Kaushik D. Meisheri
Loretta A. Cipkus
Original Assignee
The Upjohn Company
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 The Upjohn Company filed Critical The Upjohn Company
Publication of WO1988008295A1 publication Critical patent/WO1988008295A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A61Q7/02—Preparations for inhibiting or slowing hair growth
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/43—Guanidines
    • 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

Definitions

  • the present invention provides a new use for known compositions of matter. More particularly, the present invention provides topical compositions and a method for inhibiting hair growth with substituted amidines or guanidines of the Formula I.
  • Adamantyl containing guanidines are known, as disclosed in U.S. Patent 4,007,181. These compounds are useful for antiarrhythmic and diuretic uses.
  • the present invention particularly provides a topical composition for inhibiting the growth of mammalian hair comprising a compound of the Formula I, wherein R 1 and R 2 are the same or different and are
  • R 3 and R 4 when taken together with the nitrogen to which they are attached form a saturated heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-alkylpiperazino wherein the alkyl portion of the moiety is from 1 to 3 carbon atoms, inclusive, morpholino, or thiomorpholino and a vehicle adapted for topical application;
  • R 3 and R 4 when taken together with the nitrogen to which they are attached form a saturated heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-alkylpiperazino wherein the alkyl portion of the moiety is from 1 to 3 carbon atoms, inclusive, morpholino, or thiomorpholino and a vehicle adapted for topical application, in an amount effective to inhibit the growth of mammalian hair.
  • a saturated heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-alkylpiperazino wherein the alkyl portion of the moiety is from 1 to 3 carbon atoms, inclusive, morpholino, or thiomorpholino and a vehicle adapted for topical application, in an amount effective to inhibit the growth of mammalian hair.
  • Formulations for topical administration of the compounds of the present invention contain the compounds in a range of from 0.1 to 2.5% by weight of the compound. Such formulations are topically administered, daily, e.g., from 1 to 2 times daily.
  • the present invention provides treatment of various mammalian species, including humans.
  • Topical administration of the compositions of the present invention to mammals, including humans is readily undertaken by a physician or veterinarian of ordinary skill in the art.
  • N,N-di-2-adamantyl-4-morpholinecarboxamidine Most preferred is N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine.
  • Example 1 Four solutions containing 1.25, 2.5, 5.0 and 10% by weight of N- 1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine were applied to the skin of shaved rats. The 5 and 10% solution caused skin rashes and loss of body weight and the studies on these animals were discontinued. The best results were obtained with a 2.5% solution which was topically applied once a day for seven days. Hair growth ceased in the animals during treatment, but when the drug was discontinued, hair growth resumed.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides novel compositions and methods for inhibiting hair growth using adamantyl containing guanidines.

Description

HAIR GROWTH INHIBITION USING SUBSTITUTED AMIDINES OR GUANIDINES BACKGROUND OF THE INVENTION
The present invention provides a new use for known compositions of matter. More particularly, the present invention provides topical compositions and a method for inhibiting hair growth with substituted amidines or guanidines of the Formula I.
Adamantyl containing guanidines are known, as disclosed in U.S. Patent 4,007,181. These compounds are useful for antiarrhythmic and diuretic uses.
Numerous compounds which remove unwanted hair are known. However, the present invention provides compounds which inhibit the growth of hair in unwanted areas. INFORMATION DISCLOSURE Adamantyl containing guanidines are known as disclosed in U.S. Patent 4,007,181. SUMMARY OF THE INVENTION
The present invention particularly provides a topical composition for inhibiting the growth of mammalian hair comprising a compound of the Formula I, wherein R1 and R2 are the same or different and are
(a) adamantyl or a cycloalkyl of 5 to 7 carbon atoms, inclusive;
(b) R3 and R4 when taken together with the nitrogen to which they are attached form a saturated heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-alkylpiperazino wherein the alkyl portion of the moiety is from 1 to 3 carbon atoms, inclusive, morpholino, or thiomorpholino and a vehicle adapted for topical application;
2) a method for inhibiting the growth of mammalian hair comprising the topical application of a compound of the Formula I, wherein R1 and R2 are the same or different and are
(a) adamantyl or a cycloalkyl of 5 to 7 carbon atoms, inclusive;
(b) R3 and R4 when taken together with the nitrogen to which they are attached form a saturated heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-alkylpiperazino wherein the alkyl portion of the moiety is from 1 to 3 carbon atoms, inclusive, morpholino, or thiomorpholino and a vehicle adapted for topical application, in an amount effective to inhibit the growth of mammalian hair.
Compounds of Formula I are made and prepared according to U.S. Patent 4,007,181, which is expressly incorporated by reference herein. Suitable topical formulations of these compounds are disclosed in U.S. Patents 4,139,619 and 4,596,812, which are expressly incorporated by reference herein.
Formulations for topical administration of the compounds of the present invention contain the compounds in a range of from 0.1 to 2.5% by weight of the compound. Such formulations are topically administered, daily, e.g., from 1 to 2 times daily.
The present invention provides treatment of various mammalian species, including humans. Topical administration of the compositions of the present invention to mammals, including humans is readily undertaken by a physician or veterinarian of ordinary skill in the art.
Preparation of topical compositions of the compounds of the present invention is easily accomplished using known means . Those of ordinary skill in the pharmaceutical arts could readily prepare topical compositions of these compounds based on the disclosures of the U.S. patents incorporated by reference herein.
Certain of the compounds of the present invention are preferred.
N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine;
N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine hydrochloride;
N,N'-di-1-adamantyl-4-morpholinecarboxamidine;
N,N-di-1-adamantyl-4-morpholinecarboxamidine hydrochloride; and
N,N-di-2-adamantyl-4-morpholinecarboxamidine. Most preferred is N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is seen more fully by the example given below. Example 1 Four solutions containing 1.25, 2.5, 5.0 and 10% by weight of N- 1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine were applied to the skin of shaved rats. The 5 and 10% solution caused skin rashes and loss of body weight and the studies on these animals were discontinued. The best results were obtained with a 2.5% solution which was topically applied once a day for seven days. Hair growth ceased in the animals during treatment, but when the drug was discontinued, hair growth resumed.

Claims

CLAIMS 1. A topical composition for inhibiting the growth of mammalian hair comprising a compound of the Formula I
Figure imgf000006_0001
wherein R1 and R2 are the same or different and are
(a) adamantyl or a cycloalkyl of 5 to 7 carbon atoms, inclusive;
(b) R3 and R4 when taken together with the nitrogen to which they are attached form a saturated heterocyclic ring selected from the roup consisting of pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-alkylpiperazino wherein the alkyl portion of the moiety is from 1 to 3 carbon atoms, inclusive, morpholino, or thiomorpholino; and a vehicle adapted for topical application.
2. A method for inhibiting the growth of mammalian hair comprising the topical application of an amount effective to inhibit hair growth of a compound of the Formula I, wherein R1 and R2 are the same or different and are (a) adamantyl or a cycloalkyl of 5 to 7 carbon atoms, inclusive;
(b) R3 and R4 when taken together with the nitrogen to which they are attached form a saturated heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-alkylpiperazino wherein the alkyl portion of the moiety is from 1 to 3 carbon atoms, inclusive, morpholino, or thiomorpholino and a vehicle adapted for topical application, in an amount effective to inhibit the growth of mammalian hair.
3. A composition of Claim 1 containing a compound selected from the group consisting of
N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine; N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine hydrochloride;
N,N'-di-1-adamantyl-4 -morpholinecarboxamidine; N,N-di-1-adamantyl-4-morpholinecarboxamidine hydrochloride; and N,N-di-2-adamantyl-4-morpho1inecarboxamidine.
4. A method of Claim 2 containing a compound selected from the group consisting of
N-1-adamantyl-N'-eyelohexyl-4-morpholinecarboxamidine; N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine hydrochloride; N,N'-di-1-adamantyl-4-morρholinecarboxamidine;
N,N-di-1-adamantyl-4-morpholinecarboxamidine hydrochloride; and N,N-di-2-adamantyl-4-morpholinecarboxamidine.
5. A composition of Claim 3, wherein the compound is N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine.
6. A method of Claim 4, wherein the compound is N-1-adamantyl-N'-cyclohexyl-4-morpholinecarboxamidine.
PCT/US1988/000400 1987-04-23 1988-02-17 Hair growth inhibition using substitued amidines or guanidines WO1988008295A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4170887A 1987-04-23 1987-04-23
US041,708 1987-04-23

Publications (1)

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WO1988008295A1 true WO1988008295A1 (en) 1988-11-03

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0532219A2 (en) * 1991-09-04 1993-03-17 Unilever Plc Cosmetic composition
EP1477155A1 (en) * 2003-05-16 2004-11-17 The Procter & Gamble Company Compositions comprising an amidine and an alkane polyol
EP1477157A1 (en) * 2003-05-16 2004-11-17 The Procter & Gamble Company Compositions comprising an amidine and an alkane polyol
WO2010016606A2 (en) * 2008-08-05 2010-02-11 Kao Corporation Hair growth regulating agent
US9655833B2 (en) 2009-07-29 2017-05-23 Elise OLSEN Compositions and methods for inhibiting hair growth

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4007181A (en) * 1974-02-11 1977-02-08 The Upjohn Company Adamantyl containing guanidines
EP0096521A2 (en) * 1982-06-01 1983-12-21 THE PROCTER & GAMBLE COMPANY Depilatory compositions

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4007181A (en) * 1974-02-11 1977-02-08 The Upjohn Company Adamantyl containing guanidines
EP0096521A2 (en) * 1982-06-01 1983-12-21 THE PROCTER & GAMBLE COMPANY Depilatory compositions

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0532219A2 (en) * 1991-09-04 1993-03-17 Unilever Plc Cosmetic composition
EP0532219A3 (en) * 1991-09-04 1993-11-18 Unilever Plc Cosmetic composition
US5378455A (en) * 1991-09-04 1995-01-03 Chesebrough-Ponds Usa Co., Division Of Conopco, Inc. Cosmetic composition for inhibiting hair growth
EP1477155A1 (en) * 2003-05-16 2004-11-17 The Procter & Gamble Company Compositions comprising an amidine and an alkane polyol
EP1477157A1 (en) * 2003-05-16 2004-11-17 The Procter & Gamble Company Compositions comprising an amidine and an alkane polyol
WO2004103290A2 (en) * 2003-05-16 2004-12-02 The Procter & Gamble Company Compositions comprising an amidine and an alkane polyol
WO2004103290A3 (en) * 2003-05-16 2006-08-17 Procter & Gamble Compositions comprising an amidine and an alkane polyol
WO2010016606A2 (en) * 2008-08-05 2010-02-11 Kao Corporation Hair growth regulating agent
WO2010016606A3 (en) * 2008-08-05 2010-04-15 Kao Corporation Hair growth regulating agent
US8440717B2 (en) 2008-08-05 2013-05-14 Kao Corporation Hair growth regulating agent
US9655833B2 (en) 2009-07-29 2017-05-23 Elise OLSEN Compositions and methods for inhibiting hair growth
US9707169B2 (en) 2009-07-29 2017-07-18 Elise OLSEN Compositions and methods for inhibiting hair growth
US10159634B2 (en) 2009-07-29 2018-12-25 Elise A. Olsen Compositions and methods for inhibiting hair growth
EP3871671A2 (en) 2009-07-29 2021-09-01 Olsen, Elise Fp receptor antagonists for inhibiting hair growth

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