JPH0651616B2 - Salts of oxoproline with piperidinodiaminopyrimidine oxide, and compositions containing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention has the formula (I): useful in the field of pharmaceuticals and cosmetics for the treatment of pathological forms such as hair deficiency or alopecia or exfoliative dermatitis. And a salt of 5-oxoproline with 6-piperidino-2,4-diaminopyrimidine-3-oxide. Also, the formula
It also relates to a topical formulation comprising a compound of (I).

The object of the present invention is the formula (I): Is to provide a salt of 5-oxoproline and 6-piperidino-2,4-diaminopyrimidine-3-oxide.

Since the compounds of formula (I) impart a beneficial activity on the growth of hair or other body hair, they can be used in the field of cosmetics, pharmaceuticals or veterinary medicine in the form of suitable topical preparations.

Another object of the invention is the formula (I): A salt of 5-oxoproline and 6-piperidino-2,4-diaminopyrimidine-3-oxide represented by and a pharmaceutically acceptable excipient, which is used for stimulating hair growth or baldness. The purpose of the present invention is to provide a pharmaceutical composition which is applied topically to treat a disease.

Yet another object of the invention is the formula (I): The present invention provides a cosmetic composition containing the salt of 5-oxoproline and 6-piperidino-2,4-diaminopyrimidine-3-oxide represented by the formula (1) in admixture with a suitable excipient.

The 2,4-diaminopyrimidine derivative, which constitutes the basic constituent of the salt of the formula (I), is the international non-proprietary name minoxidil.
(Minoxidil) is known. This compound is currently used in the treatment of humans as an antihypertensive drug and has recently been reported for topical application in the treatment of normal baldness and alopecia areata.

Since minoxidil is water-insoluble, its liquid formulation is glycol and polyalcohol based and thus tends to make the scalp oily, thus making topical use undesirable.

On the contrary, the salts according to the invention are water-soluble and can be easily incorporated into aqueous compositions.

L-5-oxoproline, an acid compound of the salt of formula (I), also known as pyroglutamic acid (PGA), has already been used in the field of cosmetics-dermatology as a natural moisturizing component. There is. The compounds act positively to maintain optimal hydration of the hair and scalp, prevent and treat their pathological alterations.

The present inventor has developed a novel salt (hereinafter referred to as “MT /
1)) has properties particularly suitable for the prevention and treatment of hair and body hair defects. The novel compound was found to be excellent in preventing and treating hair loss when compared with minoxidil alone. In fact, it has been found that MT / 1 can be adsorbed more easily than minoxidil alone.

The novel compounds which are the object of the present invention are furthermore readily soluble in water and, due to this property, are suitable for use in formulations which are wholly or largely water-based, especially suitable for the field of trilogy.

The systemic toxicity and skin tolerance of MT / 1 are within the range of known values for minoxidil alone when administered topically. Thus, the compounds of formula (I) can be advantageously formulated in preferably wholly or predominantly aqueous lotions, creams, sprays, shampoos, gels, hair oils (brilliantine) and hair fixatives.

The composition which is the object of the present invention comprises, in addition to the compound of formula (I),
Other active ingredients with complementary activities can be included as well as the customary excipients such as fragrances, stabilizers, dyes and the like.

The composition of the invention comprises the active ingredient in a concentration of 0.1-10%,
The area to be treated is generally applied once or twice a day. No serious side effects were observed at the usual doses.

The preparation of the new compounds is done using techniques known in the art. For example, practically stoichiometric amounts of minoxidil and L-
It can be easily prepared in water by reacting with 5-oxoproline. The compounds of the present invention can be readily prepared in anhydrous or partially hydrated form using other suitable solvents such as methanol, ethanol, isopropanol and the like.

The compound of formula (I) is isolated by conventional techniques such as solvent evaporation or precipitation with a non-solvent.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.

Example 1 1.3 g of L-oxoproline was added to a suspension of 2 g of minoxidil in 50 ml of water. The resulting solution is ready for use as a preparation suitable for topical application. Alternatively, the compound can be isolated in solid form, for example by evaporating the water, preferably under low pressure. The compound of formula (I) thus obtained was chemically tested and found to be completely pure by its IR spectrum.

Example 2 95% of minoxidil 2.09 g and L-oxoproline 1.29 g
It was dissolved in 100 ml of ethanol. The resulting solution can be used as is or diluted appropriately and / or co-adjuvants or complementary substances can be added.

Alternatively, the solid compound can be isolated by complete evaporation or partial evaporation of the solvent and subsequent addition of ethyl ether as an insolubilizing agent. The solid compound obtained was chemically consistent with the compound obtained in Example 1.

Example 3 Formulation Example The composition of the salt formulation prepared according to Example 1 or Example 2 above is described below.

(a) Lotion MT / 1 3.38g Sodium ascorbate 0.5g Preservative Amount to make 100g of perfume coloring water (b) Lotion MT / 1 3.38g Vitamin H 1g Inosite (R) 1g Calcium pantothenate 1g Amino acid complex 0.2 g Vitamin B complex 5 g Isopropyl alcohol 520 g Perfume 1000 g Amount (c) Lotion MT / 1 3.38 g Turmeric (Ucon) (R) 75-H-450 10 g Vancide (R) 89 RE 0.1g Fragrance Appropriate amount Ethyl alcohol (95 ° C) 50g Amount to make water 100g (d) Aerosol lotion MT / 1 3.38g Panthenol 1g Lanogel 21 (R) 0.5g Zelek MK (R) ) (Antistatic agent) 0.1g Fragrance (Fragrance) Appropriate amount of alcohol 25g Freon (R) 11/12 (60:40) 70g (e) Lotion MT / 1 3.38g Alcohol 30g Fragrance Trace amount Colorant Appropriate amount of water 100 g (f) MT / 1.38g Resorcin 5g Capsicum tincture 5g Resin oil 5g Alcohol (90 degrees) 100g Amount Fragrance (g) Lotion MT / 1 3.38g β-naphthol 0.5g Glycerin 5g Alcohol (90 degree) 50g Fragrance (Fragrance) Appropriate amount of water 100g (h) Lotion MT / 1.38g Isopropyl alcohol 50g Fragrance (Fragrance) Appropriate amount of salicylic acid 0.2g Water 100g (i) Aerosol foam lotion MT / 1 3.38g Cetyl alcohol 0.8g Sapogenat T / 100 (R) 0.2g Neo-Extrapon H (R) 2g Iso-Adipat (R) 1g Water-soluble Neo-PSL (R) ) 2g Menthol 0.2g Emulsogen OG (R) 2g Hostaphat KL.340 (R) 2.5g Ethyl alcohol 45g Fragrance 1.2g Water 100g Amount of the above ingredients to 85g Filling propellant: 12/114 (10:60) 15g (j) Cream MT / 1 3.38g Diglycol stearate 12g Triethanolamine stearate 5g Lanolin 4g Cholesterin 5g Lecithin 0.5g Diethyl sebacate 0.5g Isopropyl myristate 10g Preservatives Water 63g (k) Shampoo MT / 1 3.38g Sucrose monolauret 50g Fragrance or colorant Water 100g Amount (l) Hair fixative MT / 1 3.84g Sodium alginate 1.2g Quench Calcium acid 0.1g Alcohol 3g Fragrance Suitable amount Preservative Suitable amount Water 100g

Claims (4)

[Claims] 1. Formula (I): A salt of 5-oxoproline with 6-piperidino-2,4-diaminopyrimidine-3-oxide. 2. Formula (I): A salt of 5-oxoproline and 6-piperidino-2,4-diaminopyrimidine-3-oxide represented by and a pharmaceutically acceptable excipient, which is used for stimulating hair growth or baldness. A pharmaceutical composition applied topically to treat a symptom. 3. Formula (I): A cosmetic composition comprising a salt of 5-oxoproline and 6-piperidino-2,4-diaminopyrimidine-3-oxide represented by the above formula in admixture with a suitable excipient. 4. A third claim in the form of a lotion, shampoo, hair fixative, cream or spray.
The cosmetic composition according to the item.