JPS58500165A - hair growth promoter - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Growth of human hair and fur-animal fur using retinoids and their derivatives Promotional technology field The present invention increases the rate of human hair growth and the growth rate of fur in certain fur animals. The invention relates to the use of retinoids and their derivatives to improve

Background technology The normal feature of hair growth in most people is that growth decreases with age; Both the rate of hair growth and the length of the growth cycle are reduced. This condition is true with one exception. It is common to all people, and in some people, male hormones, tests Clinically associated with the production of sterone and its derivatives, especially dihydrosterone It must be distinguished from true androgenetic alopecia, which is a common condition.

Many factors affect hair growth, including race, gender, age, region, season, nutrition, and hormones. affect long velocity (Myers and Hamilton, 1951; Hamilton, l 958; Yano.

1956; Maeda, 193g; Troter, 192'5; Pinku 8, 19211 and Ono, 1963). In the past, various treatments Many attempts have been made to halt the progression of androgenetic alopecia through therapy. I have tried and failed. The present invention does not intend to improve androgenetic alopecia. Main departure Ming increases the rate of hair growth from growing hair follicles and the hair follicles of some furry animals, and increases hair growth. Relates to treatments for lengthening the growth phase of the cycle.

In the past, vitamin A compounds (hereinafter referred to as retinoids) have been used to treat acne and dry skin. It has been shown to be effective in treating many diseases, including skin disease conditions such as . The inventors have discovered that retinol can be used to increase the rate of hair growth and lengthen the developmental phase of the hair cycle. I discovered a new use for retinoids.

Disclosure of invention The present inventors have discovered that retinoids, particularly all-trans retinoic acid (or retinoic acid) and Its derivatives have been shown to promote hair growth in humans and in the fluff of some furry animals. discovered to promote growth. The choice of administration includes lotions, ointments, creams, etc. It is done by local application. However, administration is not limited to these methods. , the effect can also be obtained by oral or systemic administration of retinoid compounds.

BEST MODE FOR CARRYING OUT THE INVENTION The present invention increases the rate of human hair growth and the growth rate of fluff in certain fur animals. All-trans retinoic acid and its metabolites and other retinoids Concerning the use of retinoid containing compounds. All-trans retinoic acid in cell culture High DNA synthesis in keratinocytes (specialized epidermal cells that synthesize keratin) proven to bring about success. In addition, all-trans retinoic acid is It has also been proven that it accelerates the turnover time of epidermal cells in nutritional experiments and in vivo experiments in human subjects. It is clear. The present inventor discovered that the cells of the hair follicle, including the dermal papilla, contain all-trans retinoic acid. They found that it was stimulated by retinoids, including When tested experimentally , retinoids are citritiated timidium by dermal papilla cells and root sheath cells. The cells merged into DNA and regenerated from other hair follicles at a faster rate than untreated cells.

Stimulation by this retinoid compound ultimately makes the entire hair follicle more active, causing thymidy Increasing the mitotic index, which is a measure of the incorporation of N-H into DNA. Therefore, a person's hair Grow faster and have a longer developmental phase.

The main problem in influencing hair growth is good transdermal absorption of active compounds. It is to be. Another issue is how to accurately measure hair growth to substantiate test results. It is fixed. All-trans retinoic acid and its derivatives and other retinoid compounds provides excellent transdermal absorption and is extremely effective in keratinizing skin cells, including hair follicles. It has been proven that Additionally, a relatively recent method that gives excellent results is Used to measure growth rate. This method was developed by Saitoh et al. etal) and is graduated on a 0.2 fin scale. It uses microcapillaries.

The term retinoid as used herein refers to retinol, retinal, retinyl esthetics. and retinoic acid and its esters, derivatives, and common metabolites. Was. Terminal groups can be oxidized, reduced, esterified, etc. Alkali metals (natri aluminum, potassium, etc.) and alkaline earth metals (magnesium, calcium, etc.) Also includes salts.

The pharmaceutical, cosmetic or veterinary formulations of the invention may be used as lotions, creams, etc. for the human scalp. normal methods of formulating creams, conditioners or shampoos, and For fur, veterinary formulations can be used.

Also included are orally administered preparations and compounds added to animal feed.

In addition to the active retinoids of the present invention, various formulations may be used in any conventional pharmaceutical or cosmetic form. Pharmaceutically acceptable inert or pharmaceutically active additives may also be included. . For example, lotions may contain various forms of alcohol, solvents such as glycols, or are prepared using esters. Conditioners are usually accepted and industrial For example, cetyl alcohol, ceteareth-5, -20 Trantoin, hydrolyzed animal protein, glycol stearate, amozyme Contains chicon, paraffin, mineral oil, etc. (these are listed by way of example only) (not meant to be all-inclusive). The most talked about compounds are essential fatty acids and other polyunsaturated fats. Various oils containing fatty acids and their derivatives, as well as glodiesterone, estra Also includes compounds such as hormones, including diols, thyroids, etc.

Topically applied lotions, creams, conditioners, etc. contain emulsifiers Varies by standard techniques with respect to the amounts of other hydrophilic and hydrophobic components, thus the oil Oil-based, oil-based or non-oil-based products are obtained. Use the shampoo that you normally use. containing any of the agents or soaps and other compounds used by those skilled in the art. . Oil-based shampoos fall into these mixtures.

Oral preparations can be in tablets, liquids, capsules, and the like. Preservatives, stabilizers, water Pharmaceutically acceptable substances commonly used as preservatives, emulsifiers, etc. are also included in these preparations. It can be included in a mixture. Tocopherol, N-methyl α = tocopherami butylated hydroxyanisole and butylated hydroxytoluene. Commonly accepted antioxidants can also be incorporated into the formulations of the invention.

The dosage at which a retinoid is administered depends on the route of administration and patient (subject) requirements. Therefore it changes. For topical treatment, the desired dosage in said composition is 0.00 1-2% by weight of all-trans retinoic acid or its derivatives, or other retinoic acid Lotions, creams, conditioners, shampoos, and oils containing ido Consists of treatments, etc.

Oral preparations are administered in amounts of 0.25 to 2119 per liter of body weight KP per day. this or animal food in the case of a furry animal or a dog, cat or other companion animal. It is also mixed into the food of crows in the case of birds that change their appearance.

Several experiments were conducted to investigate the special effects of retinoids on increasing the rate of hair growth. It was. Hair growth rate was measured in each case using the microcapillary method.

Table 1 shows the results of the study using male and female subjects. All-trans retinoid The acid was administered topically or in the manner shown in the table and microcapillary. The hair growth rate was therefore evaluated (see table on separate page).

Table ■ shows the results of the study using male and female subjects. All transformer type When ethyl ester of retinoic acid is administered topically or as labeled, An untreated control area was used for comparison.

The growth rate, length, thickness, and shedding period of hair in fur animals depend on the season, light ( is governed by many factors including periodicity (wavelength), temperature, hormonal factors, and nutrition. Ru. Although it is impossible to control all of these factors, it is possible to select an animal and then The half section was shaved into a 2 inch diameter circle. In some animals, that part is completely trans In other animals, retinoids are mixed into the animal's food. Administered orally. Some of the animals were compared using treated and untreated parts. served as a standard.

In fur animals, the undercoat and fur differ in thickness, length, and rate of growth. Undercoat in rabbits The average length of the fur was 3115 m, and the length of the fur was 5 CH+m. All transformer type reciprocating Topical application of noic acid was effective in increasing the rate of new hair growth.

No-shave fur treatment with all-trans retinoic acid topically in the form of a lotion The effect on the covered area was a reduction in hair removal or hair removal. Shave and treat The average hair growth rate of the five rabbits in the shaved area was 0.3 dragons/day; The average growth rate Ii of the untreated portion was 0.2 h/day.

This effect should also be demonstrated for domestic cats and dogs.

A similar experimental method was adopted. The most noticeable effect in long-haired dogs and cats is or delayed hair loss.

Long-haired dogs and cats tended to retain more hair during growth, and treatment Hair loss decreased by 50 cm during the treatment period. Both dosing regimens were satisfactory. Bureau Either a topical lotion, cream treatment, or a systemic treatment added to the animal's food. was also satisfactory. The daily dose to animals is 20 mg per kg of body weight. Mixed with food or applied topically with 10-15*y.

Commercially important fur animals have also been used in experiments. Two male mink have their back parts I harvested it with a bang.

These studies used the capillary method of measuring hair growth. those animals are food Retinoids were given as a mixture or retinoids were administered topically. Every day of The dosage is 20 μ/day per animal IKF, mixed with food or administered locally. 5xy/day was applied. These experimental results indicate that the growth rate of new villi depends on retinoid hair growth. It was shown that the treatment increased by about 30%.

Experiments with birds (canaries and parakeets) have shown that all-trans retinoic acid or all-trans retinoic acid ethyl ester of retinoic acid in the form of 3 oI per KF of bird weight per day. It was shown that when 1 g of this was mixed with food, the hair shedding process was delayed.

The following example illustrates the invention. Methods of administration include lotions, creams, ointments, pills, This includes adding it to food and applying it to bait seeds. These examples are for illustration only. Therefore, the method of administration, the ingredients mixed in the present invention, and the amount used thereof are not limited. do not have.

Example work Active ingredient: all-trans retinoic acid 0.1 ethanol q, 8. ~100, 0 Propylene glycol 5.0 Phthylated hydroxytoluene 0.1 α-tocopherol acetate O, 5 active ingredient: all-trans retinoic acid Or all-trans retinoyl acetate 10 distilled water q, s, ~1 00.0 Cetrimonium chloride 5.0 7” L-hydroxytoluene LO hydrolyzed animal protein o, 5 Methylparaben, propylparaben 0.1 case ■ All-trans retinoic acid 0. l　I/l-Dissolve in acetone IOM and The solution is UPS grade hydrophilic ointment 90! Mix with butylated hydride to achieve a uniform consistency. Add Roxitoluene II. The washable cream ointment thus prepared is Consisting of 0.1% active ingredient.

Active ingredient: all-trans retinoin a or 25 all-trans retinoic acid Tyl ester or acetate Microcrystalline cellulose lIO tar 2.5 Magnesium stearate 0.5 The above active ingredients are mixed with lactose and granulated using cornstarch paste. It turned into a situation. The remainder of the above adjuvants were mixed therein and the powder was made into tablets. next , the tablets were coated with a water-soluble or water-swellable lacquer.

Small granules can also be made by adding gelatin to the same formulation. These small The granules are then coated with lacquer. Mix the small granules with animal feed. to achieve the desired dosage level.

The above formulation can also be used in powder form for mixing with bird feed (seeds). And the bird feeder can be sprayed with lacquer.

Liquids, syrups or other mixtures may also be prepared consistent with pharmaceutical technology. can.

Table 1 Results of using all-trans retinoic acid Male 58 60897 days Oral 111 0,21 0.25 Male 21+10 Shoulder 9 Local area 10 0.35 0.119 Female 5510 Shoulder 9 Local area 50 0. 39 0.50 female 1i1 60 shoulder g oral 28 α5G 0.39 female 65 1O shoulder g local area 21 0.28] table Results of using all-trans retinoic acid ethyl ester Male 6810 Local area 2 0 0.21 0.29 Male 58 70 Oral 21 α 0.32 Female 3 610 Private area 22 0.311046 Female 112 1, Local cream 1 9 0.31 0.110 Female 6650 Oral 20 0.2111 0.29 Table ■ Male 5810 Shoulder 1 Private area 114 0.250.52 Male 24 Loll? Bureau Part 10 0.55 0.110 Female 5510■ Private part 30 0.59 0. 115 Female ill 10■ Private area 2g 0.51 0.55 Female 65Loll ? Local area 21 α2g 0.111*; Merck for commercial products and synthesis See Index.

Table 1V Male 6810 Private part 20 0.21 0.28 Male 3810 Private part 21 0 ．． 34 0.55 female 5610 private parts 22 0. i0. l+1 female B 10 Private part 19 0.59 0.4111 Female 6610 Private part 20 0.28 0.36*: Retinoic acid metabolites (i.e. 4-hydroxy and 4-keto retinoic acid metabolites) chinoic acid) which is prepared by enzymatic methods, the synthesis of which is well known.

Table 7 Subject Dosage Dosing form Treatment time Control rate Treatment growth rate (days) (-1 day ) (Town Bisao) Gender Age Male 5610 shoulder t local area 21 0jOO, 35 male 58 10mg AEJ station Part 14 0,21 0.211 Male 211 10th g Local part 10 0.35 α35 female 3510■ Private part 50 α39 0.115 female ill 10 lies Private part 280.56 0jl3 female 6510 ■ Private part 21 0.280.2 7*: g-(2,6,6-drimethyl-u-oxo prepared by enzymatic method) cyclohedis-1-enyl)-2,6-dimethyl-6-hydroxyoctatorie ner/l/ (Biochimica Biophysica and aldehyde and results of use of oxidation products including acids Male 6810 Local 20 0.21 0 ．． 25 Male 1 10 Private parts 21 0.30 0.311 Female 5610 Private parts 22 0,34 0.34 female! 2 10 Private Parts 19 0jl Q, 32 Female 6610 Local 200.21! 0.29*: Specifications are Merck Index See.

second garment Results of using all-trans retinoyl acetate Gender Age Male 36 10 towns/B Local lotion 21 0.30 0.1+5 Male 31 11 601d Oral 11 0.21 0.20 Male 2J IOQ Local 1 0 0.35 0.111 Female 55 1Qi+9 Local UOO,590,59 Female l116011g Oral 20.50 0.30 Female 6310 Shoulder g Private 21　0.28　0.39Table- Results of using all-trans chinamide

Claims (1)

[Claims] L. An effective amount of retinoid for the purpose of use, or a pharmaceutically acceptable amount thereof. by topical or oral administration of ethers, ethers, or salts to mammals. A method to increase the rate of hair growth and lengthen the growth phase of the hair cycle. a. The retinoid is all-trans retinoic acid, all-trans retinaldehyde , all-trans retinoyl salts or salts. The method described in box 1. U, the retinoid is a stereoisomer of vitamin A acid, or a stereoisomer of vitamin A, acid, and vitamin A. Tamic A acid, vitamin A acid, 5.6 epoxy vitamin A acid, dehydrovitamin Aldehydes, alcohols, esters, ethers or salts of A acids or said compounds A method according to claim 1, characterized in that the method is selected from the group consisting of: 4. The retinoid is key hydroxy retinoic acid, 4-keto retinoic acid, oxo-retinoic acid, 4-oxo-retinoic acid, 5.8-oxo-retinoic acid or 7-oxo-retinoic acid. Su-5 dehydroretinol or retinoic acid, 7-trans-9-cis-11 -trans-13-trans-terhydroxy-retinoic acid, also l-18- (2,6,6-dotsunotyl-oxocyclohedis-1-enyl)-2,6- dimethyl-6-hydroxyoctatrienal or a stereoisomer of said compound, Vitamins such as aldehydes or derivatives such as or their esters or salts The compound according to claim 1, characterized in that it is a naturally occurring metabolite of acid A. How to put it on. 5. The compound is more than crocetin, crocin or its naturally occurring metabolites. The method according to claim 1, characterized in that it is a carotenoid. & A patent application characterized in that the mammal is a human and the hair is scalp hair. The method described in item 1 of the scope of the request. 7. The animal is a furry animal and the retinoid can change or prevent hair loss. A method according to claim 1, characterized in that: 8. Topical lotions, creams, ointments, conditioners or shampoos A patent characterized in that the retinoid concentration of is within the range of 0.001 to 5% by weight. A method according to claim 1. 9. The retinoid composition is 0.25 to 20 mg per IKP of dairy animals. Claim 1, characterized in that the drug is orally administered at a dosage within a range. the method of.