CA1122531A - Diazole and a monobasic acid for hair treatment - Google Patents

Abstract

cJ,706 ABSTRACT
A hair and scalp treatment composition comprises a diazole such as imidazole and histidine or histidine derivatives, and a mono basic acid such as methionine or p-amino benzoic acid, together with a physiologically acceptable carrier. Optionally, folic acid can also be included in the composition.

Description

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The invention rela-tes to novel compositions which are capable of stimulating hair growth, and/or restoring hair gro~Yth~ and/or reducing hai.r loss in human beings.
E~cept for the palms and soles, the entire skin surface of human beings is normally hirsute. Hair grows from the cell divisions o-f matrix cells in a region known as the bulb. In all hairy animals (with the possible e~ception of merino sheep and poodle dogs) hair ~ollicles show cyclic activity. In such species as mice and rat~
all hairs are in the same state of activity, and their cyclic changes are synchronised. ~owever, in human beings and in animals such a~ guinea pigs ? the cyole o~ each follicle occurs independently from those of the neigh-la bouring follicles and show a mosaic pattern.
The hair cycle is divided into three stages : anagen(gro~ing or active stage), catagen (re~res~ive stage) and telogen (resting stage). ~he rate o~ growth of the hair varies from species to species and, in man, from region ~0 to region. ~Iring human li~e hair cycles are reproduced repeatedly. The length of hair cycle also varies from species to species and there are regional variations as ell .
~ost human body hairs grow to predictable lengths 2a peculiar to the body area and to the individual. Like all hairs they under~o periodic shedding and are replaced by other hairs of the same length. ~he number of hairs in 3L~.Z2S3~

- 3 - cJ 706 men and women are nearly the ~ame. Of 90,000-100,000 scalp hair~ in humans, irrespective of sex, about 90%
are in growing (anagen) sta~e and about 10,~ in re~ti~g (telo~en) sta~e. Human hair grows at the rate o-f about 0.3-0.4 mm per day but this is influenced by many factors.
Scalp hair in humans has been valued for its adornment value ~ince antiquity. Alopecia or scalp hair loss in man usually occurs with senility. ~owever, chronic hair lo~es in both young males and females have been observed durin~ or after psychological ~tress, high fever, ~urgical shock, treatment by antibiotics, drugs (e.g. methotrexate, 6-mercaptopurine, actinomycin D, aminopterin, 5-fluorouracil, cyclophosphamid, e-tc.), ~-ray treat~ent,j after pregnancy or after discontinuation of oral contraceptives, and, even during strict diet control. Although luxuriant growth of hair is normal and natural in most people, many people use hair tonic to promote healthy hair arowth and reduce falling hair. ~lany ~uch hair tonics contain a variety of natural substances, e.g. oil of cade, capsicum e~tract, cantharidin, jaborbandi leaf e~tract (contains alkaloid pilocarpine), oil~ from berries of Emblica afficinalis Gaertn, juice of flowers of ~ibiscus ro~a sinesi~, umblical cord and placental e~tract, e~tract of tea and coffee, etc.
~lany chemical compounds like ~ulphur-containing amino acids, cysteine or thiozolidine-4-carboxylic acid, N-acetyl homocysteine thiolactone, camphor, quinine, ~l~ZS3~
- ~ - cJ.706 ino~itol, hydrocortisone, pantothenic acid, pantothenol, linoleic acid, arachidonic acicl, etc., have all been claimed as u~eful ingredient~ for hair tonic~.
~he biological mechanisms regulating proliferation and differentiation of hair follicular cell~ are not fully understood and little is known about the cau~e of alopecia. Our studie~ ~uggest that proper balance of cyclic adeno~ine-3',5'-monophosphate (c~MP) and cyclic guanosine-3',5'-monophosphate (cG~fP) in hair bulb is one of the important factors in controlling follicular activity. Imbalance of hair bulb cA~IP and cG~iP can re~ult in increa~ed hair lo~, ultimately leading to alopecia.
We have now found that topical application of imidazole and it~ derivative~ like histidine, methionine, folic acid and p-aminobenzoic acid (PABA) tend to ~timulate hair growth in model te~t ~y~tems. We have al~o found that topical applications of coc~tail~ of imidazole or its derivative~ like hi~tidine, with methionine or P~, and with methionine + P~BA, are effective in ~timulating hair growth and in increa~ing hair dia~eter~.
The object of thi~ invention i~ to provide novel compositions which ~timulate hair gro~th and/or reduce falling hair. The in~ention accordingly provides a hair and scalp treatment composition comprisi~g a diazole chosen from imidazole, histidi~e and its salts a~d esters and mixtures thereof; and a mono~asic acid chosen from methionine, p-aminobenzoic acid and their salts and estersJand mixtures thereof, together ~ith a physiologically acceptable carrier.

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- 5 - cJ.706 ~ he composition can also optionally comprise folic acid which has been shown to provicle a fur-ther stimulus to hair growth and/or regrowth.
The composition can furthermore op-tionally colDprise inositol~ zinc or magnesium compounds such as zinc o~ide and zinc sulphate or magnesium sulphate and magnesium stearate or miYtures thereof which are believed to further contribute to an improvement in the general health of the hair and scalp.
The amounts of substances, as hereinbefore defined which, when present, can be employed in the composition are as follows:

Imidazole from 0.1 to 5.00,h, preferably from 1.0 to 3.0C~o by weight Histidine, salts or esters from 0.1 to 10.0%~ preferably thereof from 0.2 to 3 .0% by weight Folic acis, salts or from 0.1 to 5.00,b, preferably esters thereof from 0.2 to 2.00/b by weight ~ethionine, salts or from 0.1 to S.0~0, preferably 20 esters thereof from 0.2 to 3.0/~o by ~eight p-amino benzoic acid, from 0.1 to 5.00,b, preferably salts or esters thereof from 0.~ to 3.00,b by ~eight ~lyo-inositol from 0.1 to $.0%~ preferably from 0.~ to 3.0% by weight 25 Zinc o~ide or sulphate from 0.1 to 1. 5%~ preferably from 0.1 to 0.60,b by weight ~lagnesium sulphate or from 0.1 to 1. 50~h~ preferably stearate from 0.1 to 0.6% by weight Soya- or egg-lecithin from 0.1 to 5,ob~ preferably from 0.1 to 1% by weight ~2Z53~
- 6 _ cJ.706 The preferred form of histidine, ~hen employed, is the salt l-histidine monohydrochloride. The preferretl form of methionine, ~hen employed, is the isomer dl-~ethionin0 The composition according to the invention also comprises a physiologically acceptable carrier, the nature of ~hich is unimportant, provided that it is safe in use and that it does not diminish the effectiveness of the active ingredients ~Yamples of physiologically acceptable carriers are oils, fats, phospholipids such as lecithin, certain fatty acids, and long chain alcohols such as cetyl alcohol, usually in the form of an emulsion or alcoholic suspension or solution. The scope of this invention is ho~ever not limited to these examples of carriers.
The composition of the invention may be in any of the physical forms ~hich are suitable for cosmetic application to the scalp~ for e~a~ple hair creams, pourable emulsion hair dressings and alcoholic hair lotions.
The invention will now be described by way of the ~ollot~ing e~amples of hair creams, pourable emulsion hair dressings and alcoholic lotions found useful in stimulating hair grot~th and/or reducing~falling hair in human subjects.

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- 9 - cJ.706 ~ethocl of Preparation of Hair Cream ~tep I - ~li~ the ingredien-t~ of A and heat -to 50-60C
in a water bath.
II - Di~olve component~ of part B in 5-10 ml of water.
III - Di~solve components of C in 25-30 ml of di~tilled water.
IV - Heat separately A,C&D to 50-60C. Fir~t add A to D with con~tant stirring. After the mixing i5 complete then add C -to thi~ mixture with ~tirring. Finally add the ~olution of component~ of B to the mi~ture with ~tirring.
Complete the preparation with addition of perfume and remaining water. Homogeni~e the mixture to get a ~ati~factory hair dre~ing.

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- 10 - cJ.706 EklULSION HAI~ DRES~ING
Example ~ E~ample 7 E~ample 8 1. Mineral oil 19.~0 18.00 19.50 2. I~opropyl myristate 1.00 1.00 1.00 3. Cetyl alcohol 1.20 - 1.20 B 4~ Emulcol TK 2.00 - 2.00 5. Arlacel-33 1.00 1.00 1.00 6. Gelatin 0.50 - 0.50 7. Poly~inyl pyrollidone - 2.00 8. Glycerol - 5,00 9. Stearic acid - 2.00 10. Lanolin - 1.50 11. Hi~tidine 2.00 2.00 4.00 12, Methionine 0.50 0.50 0.50 13. p-Aminobenzoic acid1.50 1.00 0.8 14. Folic acid 1.00 0.50 0.50 15. Ino~itol 1.00 1.50 1.00 16. Magne~ium ~ulphate0.20 0.20 0.20 17. Zinc ~ulphate 0.40 0.~0 0.40 18. Egg lecithin 0.50 0.50 0.50 19. NaOE to pH to pH to pH
6.5-7.5 6.5-7.5 6.5-7.5 20. ~ethyl p-hydro~y benzoate 0.10 0.10 0.10 21. Perfume 0.50 0.50 0.50 22. Di~tilled water to 100 to 100 to 100 ~,~e~f~ ~rQllt ~1Ar~

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- 11 - cJ.706 ~lethocl of preparation of pourable emulsion hair clress~
I - Oil pha~e:
Heat ingreclient~ 1,2,3,4,5,9,10,18,20,21 to 50-60C.
II - Aqueous phase A:
3 ~ake a slurry of ingreclients 6,11,12,13,14,15 and to thi~ add ~ufficient amount of NaOH to bring the pE to 6.5-7.5 when a clear solution will be formed. Heat the solution to 50-60C.
III - Aqueou~ phàse B:
Di~olve ingredient~ 7,8,16 and 17 in a small amount of water and heat to 30-60C.
Fir~t mi~ the oil phase and aqueou~ pha~e A with vigorou~ stirring. To thi~ mi~ture add aqueou~ phase B
and homogenise ~everal time~.

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:: , -, - 12 - cJ.706 ~LCOHOL B~SED LOTION
Example 9 E.Yample lO Example 11 1. Isopropyl myristate 2.0 1.0 1.0 B 2. T~een-20 1.0 1.0 1.0 3 3. Alcohol 15.0 10.0 10.0

4. Isopropyl alcohol - 5.0 5.0

5. Polyvinyl pyrrolidone O.5 0.5 0.5

6. Bronidiol~ 0.1 0.1 0.1 . 7. Histidine 2.0 1.5 2.5 8. PABA 1.0 1.5 0.9 9. ~ethionine 0.1 0.2 1.0 10. Folic acid 0.3 - 0.2 11. Inositol 0.5 0.5 0.5 12. NaOH to pX to pH to pX
6.5-7.5 6.5-7.5 6.5-7.5 13. Perfume 0-5 0-5 0 5 1~. Distilled water to 100 to 100 to 100 ~lethod of preparation of lotion Prepare an aqueous slurry of ingredients 5 to 11.
To this add sufficient 20,~ aqueous ~olution of ~aOX to bring p~ to 6.5-~.5 thus obtaining a clear solution. To this solution add an aqueous alcoholic ~olution containing ingredients 1,2,g and perfume to produce an alcoholic lotion.
The co~positions as described in each of Examples 1 to 11 will significantly increase or i~prove hair ~_rowth Te5 ~r~d ~ rK

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- 13 - cJ.706 or hair regrowth lihen applied to the hair and scalp of male subjects showin~E male pattern baldness.
~xample 1~
This e~ample describes the invention in terms o~ a hair tonic formulation which was applied during the course of a clinical trial to the hair and scalp of male human subjects Hho exhibited varying degrees o~ baldness, ~air tonic formulation The hair tonic formulation employed in the clinical trial was a coconut oil based hair crea~ which contained the following ingredients:

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- 1~ - cJ.706 c,b w/~i Coconut oil 40,000 Bees wa~ 2,300 Stearic acid 2.225 .5 Cetyl alcohol 0.200 Lanolin 0.300 ~ipagin 0.100 Butyl hydro~yanisole 0.100 Egg lecithin O.aOO
Arlacel - 83 0.200 ~lagnesium sulphate, 7~2 0.510 Zinc sulphate 0.~140 L-Histidine monohydrochloride 5.000 DL_~ethionine 0.500 15 P_Aminobenzoic acid 1.000 Folic acid 0.500 Sodium hydro~ide 1.000 Perfume 0 500 Distilled water 30.000 ~0 Li~e t~ater 1'1.625 100 . 000 ll;ZZS3~L

- 13 - cJ,706 Sub,jects 22 ~ale subjects too~ part in the clinical trial, Each subject ei-5her had marked frontal baldness ~ th a noticeable bald patch on the scalp, or showed only receding hair line typical o~ the onset of male pattern baldness, Test desiFn Each subject was asked to collect daily the hairs lost - by combing, The basal daily hair loss value was detérmined for each subject for 30 days before the start of the trial with the hair tonic, The subjects were then given a tube containing about 20g hair tonic cream, and instructed to apply it once or twice a day with ~assage. Each sùbject was required to recover the hair lost daily by combing and a number of hairs lost before and after use of the cream was recorded.
Eair diameter In the case of 16 subjects, the hair diameter ~as determined on the hairs collected before use and 6 months ~0 a~ter use of the hair tonic cream. The hair diameter was measured from the hair bulb at l mm intervals up to a distance of about lO mm, It was observed that from 4 to 6 mm from the hair bulb along the hair shaft, the diameter t~as essentially constant, Hair diameter was accordingly measured at 6 mm from the hair bulb and an average value for the hair diameter ~as calculated in the case of each subject.

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- 16 - cJ,706 Results From an observation of the metlian daily hair loss of all the subjects both before and af-ter use of -the hair tonic, a general decrease in hair loss 5 became apparent after 3 months' use of the hair -tonic.
The results were analysed statistically and it was shown that there was a significant reduction in daily hair loss up to the end of the trial which was 12 months from the first application of the hair tonic.
The head of each subject was photographed at intervals during the trial, and ne~ hair growth was observed in the bald patches of most of those subjects who had bald patches at the commencement of the trial.
Of the 16 subjects whose hair diameter had been measured during the course of the trial, a s~atistically significant increase in hair diameter was observed after application of the hair tonic.
Conclusion The results of the clinical trial showed that ~0 regular use of the hair tonic cream according to the invention reduced hair loss, stimulated new growth and tended to increase hair diameter. These effects were noticeable after 3 months' application of the hair tonic cream and further improvements ~ere noted up to 12 months which marked the conclusion of the trial.

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Claims (4)

- 17 - cJ.706 CAN*

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A hair and scalp treatment composition comprising:
(a) from 0.1 to 10% by weight of a diazole selected from the group consisting of imidazole, and histidine and its salts and esters, and mixtures thereof;
(b) from 0.1 to 5% by weight of a monobasic acid selected from the group consisting of methionine, p-aminobenzoic acid and their salts and esters, and mixtures thereof;
(c) from 0.1 to 5% by weight of an acid selected from the group consisting of folic acid and its salts and esters and mixtures thereof; and (d) a physiologically acceptable carrier.

2. A composition according to claim 1, in which the diazole is histidine, and the monobasic acid is a mixture of methionine and p-aminobenzoic acid.

3. A composition according to claim 1, in which the diazole is the histidine salt, 1-histidine monohydrochloride.

4. A composition according to claim 1, in which the monobasic acid is dl-methionine.