GB2175901A - Water soluble salt of monoxidil and its use in treating hair loss - Google Patents

Abstract

The novel water-soluble salt of 5-oxoproline with 6-piperidino-2,4-diaminopyrimidine-3- oxide of the formula: <IMAGE> is employed in cosmetic and/or pharmaceutical compositions for the treatment of loss of hair or in pathological forms such as alopecia, flaking dermatitis, etc..

Description

SPECIFICATION Water soluble salt of minoxidil and its use in treating hair loss This invention relates to compounds suitable for treating hair loss in mammals and to compositions containing same.

Minoxidil is currently used in human therapy as a vasodilator antihypertensive drug and is generally taken orally in the form of tablets. Recently the topical application of Minoxidil has been disclosed in the treatment of common baldness and aerated alopecia. Minoxidil is substantially insoluble in water and liquid formulations containing Minoxidil are generally based on glycols and polyhydric alcohols. Such formulations are unpleasant for topical application as they tend to make the scalp oily.

The present invention provides water-soluble salts of Minoxidil which retain the desirable properties of Minoxidil with respect to the treatment of loss of hair.

Therefore according to the present invention there is provided the salt of 5-oxoproline with 6piperidino-2, 4-diaminopyrimidine-3-oxide having the formula

The invention also provides a cosmetic and/or pharmaceutical composition suitable for topical application comprising a compound of formula (I) as defined above together with a suitable vehicle and/or excipient.

The compound of formula (I) is endowed with activity that favours the growth of hair on the scalp and other body hairs and may be utilised in cosmetics, pharmaceutical and veterinary compositions suitable for topical application.

The acid compound of the salt of formula (I), L-5-oxoproline, also known as pyroglutamic acid (PGA) is already used in the cosmetic dermatological field as a natural moisturising factor; it acts positively by keeping optimal conditions of hydration of the hair and scalp, and by preventing and treating pathological modifications of the same.

It has been found that the salt of the invention (hereinafter referred to as MT/1) possesses properties rendering it particularly suitable for preventing and treating the loss of hair and body hairs.

The compound has been shown to be superior in preventing and treating the loss of hair and other body hairs in experiments comparing it to Minoxidil. In particular is was established that MT/1 can more easily be absorbed than Minoxidil. Furthermore, MT/1 is readily soluble in water and this property renders it particularly suitable for use in aqueous based formulations.

Both systemic toxicity and cutaneous tolerability of MT/1 are within the known values for Minoxidil when administered topically. Accordingly MT/1 can advantageously be formulated into lotions, creams, sprays, shampoo, gel, brilliantine, and hair fixers preferably in a wholly aqueous or substantially aqueous base. The formulations, may contain other active ingredients with complementary activity, as well as conventionally used vehicles and excipients such as fragrances, stabilizers, dyes, etc..

The formulations of the invention generally have a concentration of the active principle varying from 0.1 to 10% and will generally be applied on the area to be treated once or twice a day.

The preparation of MT/1 employs techniques known in the preparations of salts. For example, MT/1 may be readily prepared in water by reaction of Minoxidil with L-5-oxoproline in a substantially stoichiometric proportions.

Also the compound may be easily prepared by reaction in other suitable solvents such a methanol, ethanol, isopropanol, etc. in anhydrous or partially aqueous solvents.

The compound may be isolated by using conventional techniques, for example, evaporation of the solvent, precipitation with non-solvents, etc.

The invention will now be illustrated by the following Examples.

Example 1 1.39 L-oxoproline were added to a suspension of 29 Minoxidil in 50 ml of water.

A solution was obtained which can be used directly for the preparations of compositions suitable for topical application.

Alternatively the compound can be isolated in a solid form, for example by evaporation of water preferably under reduced pressure. The compound of formula (I) thus obtained, when analysed, was found to be perfectly pure as shown by its IR spectrum.

Example 2 2.09g of Minoxidil and 1.299 of L-oxoproline were dissolved in 100 ml of 95% ethanol. The resulting solution may be used directly or suitably diluted and/or coadjuvant or complementary substances may be added.

Alternatively, the solid compound can be isolated by total evaporation of the solvent or partial evaporation and the subsequent addition of ethyl ether as a precipitating agent.

The solid obtained corresponds chemically to that obtained in Example 1.

Example 3 Formulations The following formulations containing the salt prepared according to Examples 1 or 2 have been prepared.

a) LOTION MT/1 3.38 g Sodium ascorbate 0.5 g Preservative q.s.

Perfumed and coloured water q.s. to 100 g b) LOTION MT/1 3.38 9 Vitamin H 1 g Inosite (R) 1 g Calcium Panthotenate 1 g Amino acid complex 0.2 g Vitamin B complex 5 9 Isopropyl alcohol 520 g Perfumed Water q.s. to 1000 g c) LOTION MT/1 3.38 g Ucon (R) 75-H-450 10 g Vancide (R) 89RE 0.1 g Fragrance q.s.

Ethyl alcohol 95 degrees 50 g water q.s. to 100 g d) AEROSOL LOTION MT/1 3.38 g Panthenol 1 g Lanogel 21 (R) 0.5 g Zelek MK (R) antistatic 0. 1 g Fragrance q.s.

Alcohol 25 g Freon (R)1 1/12 (60:,40) 70 g e) LOTION MT/1 3.38 g Alcohol 30 g Fragrance Traces Colour q.s.

water q.s. to 100 g f) LOTION MT/1 3.38 g Resorcin 5 9 Tincture of capsicum 5 9 Ricin oil 5 g Alcohol 90 degrees q.s. to 100 g Fragrance q.s.

g) LOTION MT/1 3.38 g Betanaphthol 0.5 g Glycerin 5 9 Alcohol 90 degrees 50 9 Fragrance q.s.

Water q.s. to 100 g h) LOTION MT/1 3.38 g Isopropyl alcohol 50 g Fragrance q.s Salicylic acid 0.2 9 Water q.s. to 100 g i) AEROSOL FOAM LOTION MT/1 3.38 g Cetyl alcohol 0.8 g Sapogenat T/100 (R) 0.2 g Neo-Extrapon H (R) 2 g Iso-Adipat (R) 1 g Neo-PCL hydrosoluble (R) 2 g Menthol 0.2 g Emulsogen OG (R) 2 g Hostaphat KL/340 (R) 2.5 g Ethyl alcohol 45 g Fragrance 1.2 g Water q.s. to 100 g To fill: the above formulation 85 g Propellent: 121114 (10:60) 15 g j) CREAM MT/1 3.39 g Diglycol stearate 12 9 Triethanolamine stearate 5g Lanolin 49 Cholesterin 5 9 Lecithin 0.5 g Diethyl sebacate 0.5 9 Isopropyl myristate 10 g Preservative q.s.

Water 63 g k) SHAMPOO MT/1 3.38 g Saccharose monolaurate 50 g Fragrance and colour q.s.

Water q.s. to 100 g I) HAIR FIXER MT/1 3.84 g Sodium alginate 1.2 g Calcium citrate 0. 1 g Alcohol 3g Fragrance q.s.

Preservative q.s.

Water q.s. to 100 g

Claims (9)

1. The salt of 5-oxoproline with 6-piperidino-2,4-diaminopyrimidine-3-oxide having the formula

2. A salt as claimed in Claim 1 which comprises the reaction product or 5-oxoproline and 6 piperidino-2.4-diaminopyrimidine-3-oxide

3. A salt as claimed in Claim 2 in which the precursors are reacted in substantially stoichiometric proportions.

4. A salt as claimed in Claim 2 or Claim 3 in which the reaction is conducted in water or organic solvent.

5. A salt as claimed in Claim 1 substantially as herein described with reference to Examples 1 and 2.

6. A cosmetic and/or pharmaceutical composition suitable for topical application containing as active principle a compound as claimed in any preceding Claim with a suitable vehicle and/or excipient.

7. A composition as claimed in Claim 6 in the form of a lotion, shampoo, hair fixer, cream or spray.

8. A composition as claimed in Claim 6 or Claim 7 in which the active principle comprises from 0.1 to 10% of the composition.

9. A composition as claimed in Claim 6 substantially as herein described with reference to Example 3.