AU613239B2 - Salt of 6-piperidino-2,4-diaminopyrimidine 3-oxide and aceturic acid, its preparation and its dermatocosmetilogical application - Google Patents
Salt of 6-piperidino-2,4-diaminopyrimidine 3-oxide and aceturic acid, its preparation and its dermatocosmetilogical application Download PDFInfo
- Publication number
- AU613239B2 AU613239B2 AU41663/89A AU4166389A AU613239B2 AU 613239 B2 AU613239 B2 AU 613239B2 AU 41663/89 A AU41663/89 A AU 41663/89A AU 4166389 A AU4166389 A AU 4166389A AU 613239 B2 AU613239 B2 AU 613239B2
- Authority
- AU
- Australia
- Prior art keywords
- minoxidil
- aceturate
- preparation
- salt
- diaminopyrimidine
- 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.)
- Ceased
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/50—Three nitrogen atoms
-
- 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
- A61K8/4953—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 containing pyrimidine ring derivatives, e.g. minoxidil
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Plural Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
The present invention relates to Minoxidil aceturate corresponding to the formula I <IMAGE> The invention also covers the process of preparation of Minoxidil aceturate as well as its use as the active principle in dermatocosmetic compositions, in particular in hair compositions intended for the treatment of alopecia.
Description
P/00/011
.USIA
Form PATENTS ACT 1952-1973 COMPLETE SPECIFICATION
(ORIGINAL)
FOR OFFICE USE Class: Int. CI: Application Number: Lodged: o Complete Specification-Lodged: Accepted: Published: Priority: Related Art: TO BE COMPLETED BY APPLICANT Name of Applicant: NORCHIM, of 33, Quai d'Amont, 60340 Saint Leu D'Esserent, France.
Address of Applicant: Actual Inventor. -Teai-Pierre ALLAIGRE and Jacques DESBOIS cO PTUE, 0aTER 1N& 5 Address for Service: PATENT TiQA:EMARK AT ,iORNEYS 71 C,:UEENS1 ROAD, p 0, 0r04, AUST~RALU'A Complete Specification for the invention entitled: SALT OF 6-PIPERIDINO-2, 4-DIAMINOPYRIMIDINE 3-OXIDE AND ACETURIC ACID, ITS PREPARATION AND ITS DERMATOCOSMETOLOGIC- AL APPLICATION The following statement is a full description of this invention, including the best method of performing it known to me:-* 'Note: The description is to be typed in double spacing, pica type face, in an area not exceeding 250 mm in depth and 160 mm in width, on tough white paper of good quality and it is to be inserted inside this form.
11710/76-L C.J. THOMPSON. Commonwealth Government Printer, Canberra
S_.AOL
The present invention relates to minoxidil aceturate, that is to say the salt obtained by salification of minoxidil, or 6-piperidino-2,4-diaminopyrimidine 3-oxide, with aceturic acid, or acetylglycine, corresponding to the formula I N CH -C-NH-CH -COOH 0 0
NHN
2 2
(I)
0o0 0 o 0 w e The subject of the present invention also encom- O 0 o 0 oo passes the process for preparing minoxidil aceturate, as 0 00 oooo well as its use as an active principle in dermato-cos- .o.i metic compositions, especially in hair-care compositions 10 intended for the treatment of alopecia.
Minoxidil is an antihypertensive compound well known for its activity in combating hair loss, and is used on these grounds in the treatment of alopecia. As a result of its virtual insolubility in water, it has been used to date only in solutions comprising propylene glycol and ethyl alcohol, 50 to 60% by volume as regards the latter, and which are hence irritant for topical use.
The importance of the present invention consists in that, in contrast to minoxidil, which is hence virtually insoluble in water, and to aceturic acid, which is of very low water-solubility (approximately minoxidil aceturate possesses a solubility of 34% w/V at corresponding to 21.8% of active minoxidil present in the aqueous solution.
Thus, it becomes possible to prepare solutions which are either completely aqueous or which contain greatly reduced amounts of propylene glycol, the latter promoting penetration of the scalp, but henceforward lacking ethanol or any other organic solvent. All risk of skin irritation due to the presence of these solvents is 2 thereby avoided.
Minoxidil aceturate may be readily prepared by reacting minoxidil and aceturic acid in stoichiometric amounts, in an aqueous medium or in an aliphatic alcohol such as ethanol or isopropanol. The salt formed is isolated by precipitation or crystallization. This synthesis may be carried out according to Examples 1 and 2 below.
Minoxidil aceturate is a very stable, chemically well-defined crystalline compound having a melting point in the region of 155°C.
1.3 shown by chromatographic examination in aqueous solution, minoxidil aceturate is sufficiently capable of dissociation for the activity of the minoxidil to remain unchanged.
The present invention also relates to formulations for hair-care or pharmaceutical use containing minoxidil aceturate as active principle.
Examples 3 and 4 propose two possible formulations, without implied limitation.
EXAMPLE 1 20.9 g of minoxidil and 11.7 g of aceturic acid are suspended in 500 ml of ethanol.
The mixture is brought to reflux for 1 hour.
The hot solution is cooled to After filtration and drying, 29.9 g of minoxidil aceturate are recovered, corresponding to a 92% yield.
Melting point: 155"C.
The IR and NMR spectra are in agreement with the structure.
EXAMPLE 2 15.2 g of aceturic acid are suspended in 150 ml of water, and 27.2 g of minoxidil are then added with stirring. The crystals dissolve rapidly.
The solution obtained is concentrated to one third of its volume, and 650 ml of isopropanol are then added with brisk stirring. Minoxidil aceturate precipitates rapidly.
The mixture is cooled to 5 0 C and filtered. 37.3 g 3 of white crystals of minoxidil aceturate are thereby recovered, corresponding to an 88% yield. Melting point: 154-157°C.
The IR and NMR spectra are in agreement with the structure.
EXAMPLE 3 3.12 g of minoxidil aceturate are dissolved in 100 ml of distilled water.
The solution obtained, containing 2 g per 100 ml of active minoxidil, is ready for use in hair care applications.
EXAMPLE 4 4.68 g of minoxidil aceturate are dissolved in a mixture of 120 ml of distilled water and 30 ml of propylene glycol.
The solution obtained, containing the equivalent of 2 g per 100 ml of active minoxidil, is ready for use in hair care applications.
The dermato-cosmetic compositions according to the invention can assume various other forms of presentation, such as shampoos, gels, fixers or other hair-care lotions. They have, in addition, proved very effective in practice for the treatment of alopecic conditions, and have, in particular, made it possible to eliminate a number of deleterious side effects, such as irritation of the scalp or weakening of the hair through dehydration, which had been observed in the past when aqueous solutions of minoxidil were used. In addition, the improved bioavailability of the active principle according to the invention enables, with aqueous-based formulations, the concentration of available dissociated minoxidil to be lowered. Some possible problems of toxicity are thus completely solved, without a decrease in the activity in combating hair loss.
Claims (5)
1. Minoxidil aceturate corresponding to the formula I N, CH 3 NH-CH -COOH 0 0 N2 (I)
2. A process for preparing minoxidil aceturate as claimed in claim 1, wherein minoxidil and aceturic acid are reacted in stoichiometric amounts in the presence of 0 0 a solvent. 0 0
3. The process for preparing minoxidil aceturate as o claimed in claim 2, wherein the solvent used is prefer- ably water or an alcohol such as ethyl or isopropyl alcohol.
4. Dermato-cosmetic compositions, which contain minoxidil aceturate as claimed in claim 1 as active principle, mixed with an aqueous-based vehicle. o a
5. Minoxidil aceturate, process for preparing same and 0oG dermato-cosmetic compositions containing same substantially as hereinbefore described with reference to any one or more '1 of the examples. DATED this 25th day of September, 1989. NORCHIM 9IE, .cATE p PATENT TADUaMARK SQUEENS ROAD, ;I-i SO
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8812442A FR2636840B1 (en) | 1988-09-23 | 1988-09-23 | SALT OF 6-PIPERIDINO-2,4-DIAMINOPYRIMIDINE-3-OXIDE AND ACETURIC ACID, THEIR PREPARATION AND THEIR DERMATOCOSMETOLOGICAL APPLICATIONS |
| FR8812442 | 1988-09-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU4166389A AU4166389A (en) | 1990-03-29 |
| AU613239B2 true AU613239B2 (en) | 1991-07-25 |
Family
ID=9370311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU41663/89A Ceased AU613239B2 (en) | 1988-09-23 | 1989-09-25 | Salt of 6-piperidino-2,4-diaminopyrimidine 3-oxide and aceturic acid, its preparation and its dermatocosmetilogical application |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0362030B1 (en) |
| AT (1) | ATE78154T1 (en) |
| AU (1) | AU613239B2 (en) |
| CA (1) | CA1323030C (en) |
| DE (1) | DE68902122T2 (en) |
| ES (1) | ES2042033T3 (en) |
| FR (1) | FR2636840B1 (en) |
| GR (1) | GR3005413T3 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8918709D0 (en) * | 1989-08-16 | 1989-09-27 | Unilever Plc | Cosmetic composition |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU590431B2 (en) * | 1986-10-07 | 1989-11-02 | Farmos-Yhtyma Oy | A method for the preparation of 2,4-diamino-3-oxy-6- piperidyl-pyrimidine |
| AU594709B2 (en) * | 1985-10-10 | 1990-03-15 | Crinos Industria Farmacobiologica S.P.A. | Hair stimulating compound |
| AU595105B2 (en) * | 1987-04-22 | 1990-03-22 | Farmos-Yhtyma Oy | Preparation 2,4-diamino-3-oxy-6-piperidyl pyrimidine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1020558A (en) * | 1971-04-07 | 1977-11-08 | Richard C. Thomas (Jr.) | 6-amino-4-(substituted amino)-1,2-dihydro-1-hydroxy-2-iminopyrimidines |
| IL78842A0 (en) * | 1985-05-22 | 1986-09-30 | Serono Otc Sa | Piperidino-pyridine derivatives and pharmaceutical and cosmetic compositions containing them |
| FR2590897B1 (en) * | 1985-12-06 | 1988-02-19 | Kemyos Bio Medical Research Sr | NOVEL DERIVATIVES OF 6 AMINO 1,2-DIHYDRO-1-HYDROXY-2-IMINO-PYRIMIDINE, THEIR PREPARATION PROCESS AND COSMETIC COMPOSITIONS CONTAINING THEM |
-
1988
- 1988-09-23 FR FR8812442A patent/FR2636840B1/en not_active Expired - Fee Related
-
1989
- 1989-09-20 CA CA000612139A patent/CA1323030C/en not_active Expired - Lifetime
- 1989-09-21 AT AT89402592T patent/ATE78154T1/en not_active IP Right Cessation
- 1989-09-21 ES ES198989402592T patent/ES2042033T3/en not_active Expired - Lifetime
- 1989-09-21 EP EP89402592A patent/EP0362030B1/en not_active Expired - Lifetime
- 1989-09-21 DE DE8989402592T patent/DE68902122T2/en not_active Expired - Lifetime
- 1989-09-25 AU AU41663/89A patent/AU613239B2/en not_active Ceased
-
1992
- 1992-08-11 GR GR920401740T patent/GR3005413T3/el unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU594709B2 (en) * | 1985-10-10 | 1990-03-15 | Crinos Industria Farmacobiologica S.P.A. | Hair stimulating compound |
| AU590431B2 (en) * | 1986-10-07 | 1989-11-02 | Farmos-Yhtyma Oy | A method for the preparation of 2,4-diamino-3-oxy-6- piperidyl-pyrimidine |
| AU595105B2 (en) * | 1987-04-22 | 1990-03-22 | Farmos-Yhtyma Oy | Preparation 2,4-diamino-3-oxy-6-piperidyl pyrimidine |
Also Published As
| Publication number | Publication date |
|---|---|
| CA1323030C (en) | 1993-10-12 |
| ES2042033T3 (en) | 1993-12-01 |
| FR2636840A1 (en) | 1990-03-30 |
| AU4166389A (en) | 1990-03-29 |
| FR2636840B1 (en) | 1990-12-21 |
| ATE78154T1 (en) | 1992-08-15 |
| GR3005413T3 (en) | 1993-05-24 |
| DE68902122D1 (en) | 1992-08-20 |
| EP0362030B1 (en) | 1992-07-15 |
| DE68902122T2 (en) | 1992-12-03 |
| EP0362030A1 (en) | 1990-04-04 |
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