WO1992007569A1 - Alteration of rate and character of hair growth - Google Patents
Alteration of rate and character of hair growth Download PDFInfo
- Publication number
- WO1992007569A1 WO1992007569A1 PCT/US1991/007839 US9107839W WO9207569A1 WO 1992007569 A1 WO1992007569 A1 WO 1992007569A1 US 9107839 W US9107839 W US 9107839W WO 9207569 A1 WO9207569 A1 WO 9207569A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- inhibitor
- rate
- hair growth
- character
- composition
- Prior art date
Links
- 230000003779 hair growth Effects 0.000 title claims abstract description 18
- 230000004075 alteration Effects 0.000 title 1
- 239000003112 inhibitor Substances 0.000 claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 16
- 102000005291 Adenylosuccinate synthase Human genes 0.000 claims abstract description 8
- 108010056443 Adenylosuccinate synthase Proteins 0.000 claims abstract description 8
- 230000000699 topical effect Effects 0.000 claims abstract description 8
- 102000030907 Aspartate Carbamoyltransferase Human genes 0.000 claims abstract description 7
- 108091000126 Dihydroorotase Proteins 0.000 claims abstract description 7
- ZZKNRXZVGOYGJT-VKHMYHEASA-N (2s)-2-[(2-phosphonoacetyl)amino]butanedioic acid Chemical group OC(=O)C[C@@H](C(O)=O)NC(=O)CP(O)(O)=O ZZKNRXZVGOYGJT-VKHMYHEASA-N 0.000 claims description 10
- ZGNLFUXWZJGETL-YUSKDDKASA-N (Z)-[(2S)-2-amino-2-carboxyethyl]-hydroxyimino-oxidoazanium Chemical group N[C@@H](C\[N+]([O-])=N\O)C(O)=O ZGNLFUXWZJGETL-YUSKDDKASA-N 0.000 claims description 10
- MLFKVJCWGUZWNV-UHFFFAOYSA-N L-alanosine Natural products OC(=O)C(N)CN(O)N=O MLFKVJCWGUZWNV-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 7
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 description 16
- 210000004209 hair Anatomy 0.000 description 8
- 241000699800 Cricetinae Species 0.000 description 7
- 210000003780 hair follicle Anatomy 0.000 description 7
- 210000003491 skin Anatomy 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 235000013928 guanylic acid Nutrition 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- -1 β-D-arabinosyl guanosine monophosphate Chemical compound 0.000 description 2
- ZCARDBJHSMTFCZ-UHFFFAOYSA-N 2-(phosphonomethylsulfanylmethyl)butanedioic acid Chemical compound OC(=O)CC(C(O)=O)CSCP(O)(O)=O ZCARDBJHSMTFCZ-UHFFFAOYSA-N 0.000 description 1
- NOIIUHRQUVNIDD-UHFFFAOYSA-N 3-[[oxo(pyridin-4-yl)methyl]hydrazo]-N-(phenylmethyl)propanamide Chemical compound C=1C=CC=CC=1CNC(=O)CCNNC(=O)C1=CC=NC=C1 NOIIUHRQUVNIDD-UHFFFAOYSA-N 0.000 description 1
- WCBBDNWGSPGKPP-REOHCLBHSA-N 4-amino-2-[(2s)-2-amino-3-[hydroxy(nitroso)amino]propanoyl]-1h-imidazole-5-carboxylic acid Chemical compound O=NN(O)C[C@H](N)C(=O)C1=NC(C(O)=O)=C(N)N1 WCBBDNWGSPGKPP-REOHCLBHSA-N 0.000 description 1
- QOVIBFFZCVPCEI-UMMCILCDSA-N 5-amino-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6H-triazolo[4,5-d]pyrimidin-7-one Chemical compound N1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O QOVIBFFZCVPCEI-UMMCILCDSA-N 0.000 description 1
- MJJUWOIBPREHRU-MWKIOEHESA-N 7-Deaza-8-azaguanosine Chemical compound NC=1NC(C2=C(N=1)N(N=C2)[C@H]1[C@H](O)[C@H](O)[C@H](O1)CO)=O MJJUWOIBPREHRU-MWKIOEHESA-N 0.000 description 1
- NKGPJODWTZCHGF-UHFFFAOYSA-N 9-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound OC1C(O)C(CO)OC1N1C(NC=NC2=S)=C2N=C1 NKGPJODWTZCHGF-UHFFFAOYSA-N 0.000 description 1
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 1
- 101710107035 Gamma-glutamyltranspeptidase Proteins 0.000 description 1
- 101710173228 Glutathione hydrolase proenzyme Proteins 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 1
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- MLFKVJCWGUZWNV-REOHCLBHSA-N alanosine Chemical compound OC(=O)[C@@H](N)CN(O)N=O MLFKVJCWGUZWNV-REOHCLBHSA-N 0.000 description 1
- 102000001307 androgen receptors Human genes 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QQWGVQWAEANRTK-UHFFFAOYSA-N bromosuccinic acid Chemical compound OC(=O)CC(Br)C(O)=O QQWGVQWAEANRTK-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000002951 depilatory effect Effects 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940116298 l- malic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 239000002719 pyrimidine nucleotide Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
-
- 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
- A61K8/55—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
-
- 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
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Definitions
- This invention relates to a method and composition for altering the rate and character of mammalian hair growth, particularly androgen-stimulated hair growth, by topical application to the skin of a composition containing an inhibitor of adenylosuccinate synthetase or of aspartate transcarbamylase.
- inhibitors of adenylosuccinate synthetase which may be used in the present invention are L-alanosine ([L-2-amino-3-(N-hydroxy, N-nitrosamino) propionic acid]), 6-mercaptopurine riboside 5'- phosphate, 8-aza guanosine monophosphate, 7-deaza-8-aza guanosine monophosphate, 2'-d guanosine monophosphate, ⁇ -D-arabinosyl guanosine monophosphate and the like.
- Inhibitors of aspartate transcarbamylase include N- phosphonacetyl-L-aspartic acid (PALA), 2-
- L-alanosine and PALA are preferred. It should be noted that L-alanosine is metabolically activated to L-alanosyl-5-amino-4-imidazole carboxylic acid
- ribonucleotide which is formed in vivo and which is the direct or proximate inhibitor of the enzyme
- L-alanosine is thus an indirect inhibitor of the enzyme but is included within the term inhibitor for the purpose of the present invention.
- the composition of the present invention contains, in addition to the inhibitor, a non-toxic dermatologically acceptable vehicle or carrier which is adapted to be spread upon the skin.
- concentration of the inhibitor in the composition may be varied over a wide range up to a saturated solution, preferably from 0.1 to 20% by weight or even more; the reduction of hair growth increases as the amount of inhibitor applied increases per unit area of skin.
- the maximum amount effectively applied is limited only by the rate at which the inhibitor penetrates the skin. Generally, the effective amounts range from 10 to 2500 micrograms or more per square centimeter of skin.
- a vehicle or carrier was prepared having the following composition:
- L-alanosine was mixed with separate portions of the foregoing vehicle to provide specimens containing 0.1, 0.5, 1, 2, and 6% by weight respectively of the inhibitor and the pH was adjusted to pH 7.5 with sodium hydroxide.
- the hair on the treated organ was also observed to be more vellous in nature than that on the untreated organ.
- L-alanosine caused reduction in AMP, ADP, and ATP levels in hair follicles by 50, 40 and 29%, respectively.
- N- phosphonacetyl-L-aspartic acid (PALA) in the vehicle described in Example 1 above adjusted to pH 4.5 , and applied to hamster flank organs under the same
- the effect of PALA administration on pyrimidine nucleotide content of hair follicles was determined, using the same treatment protocol as for determining nucleotide content in Example 1.
- the results were inhibition of UDP by 25% , UTP by 50% , CDP by 19%, and CTP by 60% .
Abstract
The rate and character of mammalian hair growth is altered by the topical application to the skin of a composition containing an inhibitor of the enzymes adenylosuccinate synthetase or aspartate transcarbamylase.
Description
ALTERATION OF RATE AND CHARACTER OF HAIR GROWTH
This invention relates to a method and composition for altering the rate and character of mammalian hair growth, particularly androgen-stimulated hair growth, by topical application to the skin of a composition containing an inhibitor of adenylosuccinate synthetase or of aspartate transcarbamylase.
It has previously been proposed to alter the rate and character of hair growth by applying to the skin inhibitors of certain enzymes such as inhibitors of 5-alpha-reductase or of ornithine decarboxylase, or such antiandrogen materials as cytoplasmic androgen receptor binding agents, as described in U.S. Patents Nos.
4,720,489 and 4,885,289. Moreover, it has been
theorized that other enzymes, including gamma glutamyl transpeptidase, are involved in various stages of hair follicle formation or of hair growth, but the relation between the various enzymes and the reactions which they control, as well as their effect upon each other and upon hair growth, has not been fully understood, as appears from Richards et al. Cancer Research, Vol. 42, 4143-4152 (1982); DeYoung et al. Cancer Research, Vol. 38, 3697-3701 (1978); and Chase, Physiolo. Zool., Vol. 24, 1-8 (1951).
It has now been found that the rate and character of mammalian (including human) hair growth, particularly androgen-stimulated hair growth, is altered by topical application to the skin of a composition containing an inhibitor of adenylosuccinate synthetase
or of aspartate transcarbamylase.
Among the inhibitors of adenylosuccinate synthetase which may be used in the present invention are L-alanosine ([L-2-amino-3-(N-hydroxy, N-nitrosamino) propionic acid]), 6-mercaptopurine riboside 5'- phosphate, 8-aza guanosine monophosphate, 7-deaza-8-aza guanosine monophosphate, 2'-d guanosine monophosphate, β-D-arabinosyl guanosine monophosphate and the like. Inhibitors of aspartate transcarbamylase include N- phosphonacetyl-L-aspartic acid (PALA), 2-
[[(phosphonomethyl) thio] methyl] succinic acid, O- phosphonoacetyl-L-malic acid, halogenated
phosphonoacetyldioic or halogenated phosphonoacetyl aminodioic acids as described in European Patent
Application 328,834 A, and bromosuccinate, among others. Of these, L-alanosine and PALA are preferred. It should be noted that L-alanosine is metabolically activated to L-alanosyl-5-amino-4-imidazole carboxylic acid
ribonucleotide, which is formed in vivo and which is the direct or proximate inhibitor of the enzyme
adenylosuccinate synthetase. L-alanosine is thus an indirect inhibitor of the enzyme but is included within the term inhibitor for the purpose of the present invention.
The composition of the present invention contains, in addition to the inhibitor, a non-toxic dermatologically acceptable vehicle or carrier which is adapted to be spread upon the skin. The concentration of the inhibitor in the composition may be varied over a wide range up to a saturated solution, preferably from 0.1 to 20% by weight or even more; the reduction of hair growth increases as the amount of inhibitor applied increases per unit area of skin. The maximum amount effectively applied is limited only by the rate at which the inhibitor penetrates the skin. Generally, the effective amounts range from 10 to 2500 micrograms or more per square centimeter of skin.
The following specific examples are intended to illustrate more clearly the nature of the present invention without acting as a limitation upon its scope.
Example 1
A vehicle or carrier was prepared having the following composition:
Component Wt. Percent Concentration Water 68%
Ethanol 16%
Propylene Glycol 5%
Dipropylene Glycol 5%
Benzyl Alcohol 4%
Propylene Carbonate 2%
L-alanosine was mixed with separate portions of the foregoing vehicle to provide specimens containing 0.1, 0.5, 1, 2, and 6% by weight respectively of the inhibitor and the pH was adjusted to pH 7.5 with sodium hydroxide.
Four groups (eight animals in each group) of male intact Golden Syrian hamsters were provided. These animals were considered acceptable models for human beard hair growth in that they display oval shaped flank organs, one on each side, each about 8 mm. in major diameter, which grow thick black and coarse hair similar to human beard hair. These organs produce hair in response to androgens in the hamster. The flank organs of each hamster were depilated by applying a
thioglycolate- based chemical depilatory (Surgex), and to one organ of each animal was applied 10-25 μl. of vehicle alone once a day, while to the other organ of each animal was applied an equal amount of vehicle containing inhibitor. After three weeks of such
applications (five days a week), the flank organs were shaved and the amount of recovered hair (hair mass) from each was weighed. The extent of reduction in hair growth by the inhibitor was expressed as the percent decrease in hair mass on the organ treated with
inhibitor as compared to the organ treated with vehicle alone. As a control, one group of eight animals had both flank organs of each animal treated with vehicle alone. The results were as shown in Table 1 below.
Table 1
Inhibition of Hair Growth by L- Hamster Flank organ Hair Mass (mg)
The hair on the treated organ was also observed to be more vellous in nature than that on the untreated organ.
In addition, it was found that similar topical treatments with a 10% solution of L-alanosine, twice over a 24 hour period, resulted in about 49% inhibition of adenylosuccinate synthetase activity in the hamster hair follicles.
The effect of the enzyme inhibition, was further shown by measurements of hair follicle
nucleotide levels after topical treatment with L- alanosine. A group of eight hamsters was treated topically with L-alanosine (10 % in the vehicle above) on one flank organ while the other organ received an equal amount of just the vehicle. After three days of daily treatments, the hair follicles from the flank organs were removed and the adenosine nucleotide contents were determined. L-alanosine treatment caused reduction in AMP, ADP, and ATP levels in hair follicles by 50, 40 and 29%, respectively.
Example 2
A series of compositions was prepared
containing various percentages by weight of N-
phosphonacetyl-L-aspartic acid (PALA) in the vehicle described in Example 1 above adjusted to pH 4.5 , and applied to hamster flank organs under the same
conditions as described in Example 1. The reduction in hair growth observed after three weeks was as follows :
Table 2
INHI I LA LANK mg
It was found that similar topical treatments with a 10% solution of PALA (two treatments with a 10% solution of PALA (over a 24 hour period) resulted in a 72% reduction of aspartate transcarbamylase activity in the hamster hair follicles.
The effect of PALA administration on pyrimidine nucleotide content of hair follicles was determined, using the same treatment protocol as for determining nucleotide content in Example 1. The results were inhibition of UDP by 25% , UTP by 50% , CDP by 19%, and CTP by 60% .
Claims
1. The process of reducing the rate and altering the character of mammalian hair growth which comprises the step of applying to the skin a composition containing an inhibitor of adenylosuccinate synthetase.
2. The process as claimed in claim 1, in which said inhibitor is L-alanosine.
3. The process as claimed in claim 1 or claim 2, in which the rate of applying is from 10 to 2500 micrograms of said inhibitor per square centimeter of skin.
4. The process of reducing the rate and altering the character of mammalian hair growth which comprises the step of applying to the skin a composition containing an inhibitor of aspartate transcarbamylase.
5. The process as claimed in claim 4, in which said inhibitor is N-phosphonacetyl-L-aspartic acid.
6. The process as claimed in claim 1 or claim 2, in which the rate of applying is from 10 to 2,500 micrograms of said inhibitor per square centimeter of skin.
7. A topical composition for reducing the rate and altering the character of mammalian hair growth comprising a non-toxic dermatologically acceptable vehicle and from 0.1 to 20%, based on the total weight of said composition, of an inhibitor of adenylosuccinate synthetase.
8. A composition as claimed in claim 7, in which said inhibitor is L-alanosine.
9. A topical composition for reducing the rate and altering the character of mammalian hair growth comprising a non-toxic dermatologically acceptable vehicle and from 0.1 to 20%, based on the total weight of said composition, of an inhibitor of aspartate transcarbamylase.
10. A composition as claimed in claim 9, in which said inhibitor is N-phosphonacetyl-L-aspartic acid.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE69129663T DE69129663T2 (en) | 1990-10-24 | 1991-10-22 | CHANGE OF SPEED AND CHARACTER OF HAIR GROWTH |
| EP91920173A EP0554363B1 (en) | 1990-10-24 | 1991-10-22 | Alteration of rate and character of hair growth |
| CA002094491A CA2094491C (en) | 1990-10-24 | 1991-10-22 | Alteration of rate and character of hair growth |
| AU89289/91A AU662112B2 (en) | 1990-10-24 | 1991-10-22 | Alteration of rate and character of hair growth |
| JP50125792A JP3532192B2 (en) | 1990-10-24 | 1991-10-22 | Changes in hair growth rate and characteristics |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US603,999 | 1990-10-24 | ||
| US07/603,999 US5095007A (en) | 1990-10-24 | 1990-10-24 | Alteration of rate and character of hair growth |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992007569A1 true WO1992007569A1 (en) | 1992-05-14 |
Family
ID=24417775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1991/007839 WO1992007569A1 (en) | 1990-10-24 | 1991-10-22 | Alteration of rate and character of hair growth |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5095007A (en) |
| EP (1) | EP0554363B1 (en) |
| JP (1) | JP3532192B2 (en) |
| AT (1) | ATE167625T1 (en) |
| AU (1) | AU662112B2 (en) |
| CA (1) | CA2094491C (en) |
| DE (1) | DE69129663T2 (en) |
| ES (1) | ES2117646T3 (en) |
| WO (1) | WO1992007569A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018118808A1 (en) | 2016-12-19 | 2018-06-28 | The Broad Institute, Inc. | Methods of treating autism spectrum disorders |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9118866D0 (en) * | 1991-09-04 | 1991-10-23 | Unilever Plc | Cosmetic composition |
| JPH07504646A (en) * | 1991-11-05 | 1995-05-25 | ザ、ジレット、カンパニー | Changes in the speed and characteristics of hair growth |
| US5364885A (en) * | 1992-11-13 | 1994-11-15 | Ahluwalia Gurpreet S | Reduction of hair growth |
| US6743419B1 (en) | 1992-12-22 | 2004-06-01 | The Gillette Company | Method of reducing hair growth employing sulfhydryl active compounds |
| US5411991A (en) * | 1992-12-22 | 1995-05-02 | Shander; Douglas | Method of reducing hair growth employing sulfhydryl active compounds |
| US5648394A (en) * | 1993-05-27 | 1997-07-15 | Boxall; Brian Alfred | Topical composition for inhibiting hair growth |
| US6414017B2 (en) | 1993-05-28 | 2002-07-02 | The Gillette Company | Inhibition of hair growth |
| US6239170B1 (en) | 1993-05-28 | 2001-05-29 | Gurpreet S. Ahluwalia | Inhibition of hair growth |
| US5474763A (en) * | 1994-03-11 | 1995-12-12 | Shander; Douglas | Reduction of hair growth |
| US5455234A (en) * | 1994-03-16 | 1995-10-03 | Ahluwalia; Gurpreet S. | Inhibition of hair growth |
| US5468476A (en) * | 1994-03-16 | 1995-11-21 | Ahluwalia; Gurpreet S. | Reduction of hair growth |
| US5554608A (en) * | 1994-09-28 | 1996-09-10 | Ahluwalia; Gurpreet S. | Inhibition of hair growth |
| US5674477A (en) * | 1995-02-28 | 1997-10-07 | Ahluwalia; Gurpreet S. | Reduction of hair growth |
| DE69622154T2 (en) * | 1995-02-28 | 2003-02-13 | Gillette Co | USE OF ANGIOGENESE SUPPRESSORS TO INHIBIT HAIR GROWTH |
| US5645825A (en) * | 1995-06-07 | 1997-07-08 | The Procter & Gamble Company | Depilatory compositions comprising sulfhydryl compounds |
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| US20060263438A1 (en) * | 2005-05-17 | 2006-11-23 | L'oreal | Gelled oil particles for targeting sebaceous glands and/or hair follicles |
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| US20070059264A1 (en) * | 2005-09-13 | 2007-03-15 | Ahluwalia Gurpreet S | Reduction of hair growth |
| US7727516B2 (en) * | 2006-02-28 | 2010-06-01 | The Procter & Gamble Company | Reduction of hair growth |
| FR2944443B1 (en) | 2009-04-21 | 2012-11-09 | Arkema France | METHOD FOR MANUFACTURING IMPREGNATED FREE POLYAMIDE FREE POWDER PARTICLES, AND POLYAMIDE FREE POWDER PARTICLES HAVING A CONTENT OF AT LEAST 25% BY WEIGHT OF AT LEAST ONE COSMETIC OR PHARMACEUTICAL AGENT |
| FR2953716B1 (en) | 2009-12-16 | 2015-03-27 | Oreal | KIT FOR FORMULATING A COSMETIC PRODUCT |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4720489A (en) * | 1984-10-15 | 1988-01-19 | Douglas Shander | Hair growth modification with ornithine decarboxylase inhibitors |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4720480A (en) * | 1985-02-28 | 1988-01-19 | Dai Nippon Insatsu Kabushiki Kaisha | Sheet for heat transference |
| FR1505475A (en) * | 1966-10-25 | 1967-12-15 | Docteur Jacques Auclair Lab Du | Cosmetic composition |
| BE793306A (en) * | 1971-12-23 | 1973-04-16 | Waldhof Aschaffenburg Papier | COSMETIC PRODUCT |
| US4885289A (en) * | 1983-12-12 | 1989-12-05 | Breuer Miklos M | Alteration of character of male beard growth |
| EP0328834A1 (en) * | 1988-02-16 | 1989-08-23 | Merrell Dow Pharmaceuticals Inc. | Novel aspartate transcarbamylase inhibitors |
| SE466826B (en) * | 1990-06-28 | 1992-04-06 | Asea Brown Boveri | MANUFACTURED TO MANUFACTURE A METAL OXID VARISTOR WITH FORBETTRAD ENERGY QUALITY |
-
1990
- 1990-10-24 US US07/603,999 patent/US5095007A/en not_active Expired - Lifetime
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1991
- 1991-10-22 ES ES91920173T patent/ES2117646T3/en not_active Expired - Lifetime
- 1991-10-22 JP JP50125792A patent/JP3532192B2/en not_active Expired - Lifetime
- 1991-10-22 EP EP91920173A patent/EP0554363B1/en not_active Expired - Lifetime
- 1991-10-22 DE DE69129663T patent/DE69129663T2/en not_active Expired - Lifetime
- 1991-10-22 AU AU89289/91A patent/AU662112B2/en not_active Expired
- 1991-10-22 AT AT91920173T patent/ATE167625T1/en not_active IP Right Cessation
- 1991-10-22 WO PCT/US1991/007839 patent/WO1992007569A1/en active IP Right Grant
- 1991-10-22 CA CA002094491A patent/CA2094491C/en not_active Expired - Lifetime
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4720489A (en) * | 1984-10-15 | 1988-01-19 | Douglas Shander | Hair growth modification with ornithine decarboxylase inhibitors |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018118808A1 (en) | 2016-12-19 | 2018-06-28 | The Broad Institute, Inc. | Methods of treating autism spectrum disorders |
| US11273161B2 (en) | 2016-12-19 | 2022-03-15 | The Broad Institute, Inc. | Methods of treating autism spectrum disorders |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE167625T1 (en) | 1998-07-15 |
| AU8928991A (en) | 1992-05-26 |
| AU662112B2 (en) | 1995-08-24 |
| JP3532192B2 (en) | 2004-05-31 |
| CA2094491A1 (en) | 1992-04-25 |
| EP0554363A1 (en) | 1993-08-11 |
| ES2117646T3 (en) | 1998-08-16 |
| EP0554363A4 (en) | 1993-09-15 |
| DE69129663D1 (en) | 1998-07-30 |
| JPH06502648A (en) | 1994-03-24 |
| EP0554363B1 (en) | 1998-06-24 |
| CA2094491C (en) | 2003-01-28 |
| DE69129663T2 (en) | 1999-01-21 |
| US5095007A (en) | 1992-03-10 |
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