KR20030080497A - Use of gossypol and its derivatives for hair growth - Google Patents

Abstract

PURPOSE: A composition containing gossypol or a derivative thereof as a component of various plants such as Gossypium nanking Meyen and Gossypii Semen as a main component is provided. Therefore, it shows excellent hair growing effects. CONSTITUTION: The composition for promoting hair growth contains gossypol or a derivative thereof represented by the formula 1. In formula, R1 is C0-R2 or CH=N-R2 or cyano; R2 is H, C1-6 straight or branched alkyl, alkenyl, alkynyl or acyl and also contains a substituent in which R2 is substituted with one or more of amino, hydroxy, halo, haloalkyl, alkoxy, cyano, nitro, alkylamino, dialkylamino and the like, preferably R2 is H, namely, R1 may be COH(aldehyde); R3 is H, C1-6 straight or branched alkyl, alkenyl, alkynyl or acyl and also contains a substituent in which R3 is substituted with one or more of amino, hydroxy, halo, haloalkyl, alkoxy, cyano, nitro, alkylamino, dialkylamino and the like, preferably R3 is H; R4 is H, C1-6 straight or branched alkyl, alkenyl, alkynyl or acyl and also contains a substituent in which R4 is substituted with one or more of amino, hydroxy, halo, haloalkyl, alkoxy, cyano, nitro, alkylamino, dialkylamino and the like, preferably R4 is H.

Description

Hair growth promoter containing Gosipol or its derivatives as an active ingredient {Use of gossypol and its derivatives for hair growth}

The present invention is a hair containing Gossypol (Gossypol) or a derivative thereof, which is a component of various plants such as cotton (Gossypium nanking Meyen (Mallow and Malvaceae) and seeds of the same plant (cotton, cotton, Gossypii semen) It relates to a growth accelerator.

The human hair is about 100,000 to 150,000 pieces, and each hair has a different cycle and grows and drops out through the anagen, the catagen, and the telogen. This cycle is repeated over three to six years, with the result that on average 50 to 100 hairs fall out normally. Generally, the term alopecia refers to the increase in the number of hairs that fall abnormally due to shortening of the hair growth rate in the growth phase and more hair in the degenerative or resting phase.

The causes of alopecia have been discussed, such as poor blood circulation, excessive male hormone action, excessive sebum secretion, peroxide, bacteria, hypodermic function, genetic factors, aging, stress. However, to date, no clear cause of hair loss is known, and in recent years, a growing number of people are suffering from hair loss due to changes in diet and stress caused by social conditions. It is increasing.

The most widely used formulations for the treatment or prevention of such alopecia to date are minoxidil-containing formulations, and are currently one of two hair repellent components approved by the US FDA. Minoxidil was a drug for hypertension that was developed for the purpose of lowering blood pressure, but with the side effect of use, hair growth phenomenon has now become a more famous drug for hair growth. Although the mechanism of minoxidil's hair growth is not known exactly, it is thought to promote hair growth by nourishing hair roots by increasing blood flow through vasodilating effect.

This model of increased blood flow has recently been reported that minoxidil increases the expression of vascular endothelial growth factor (VEGF), a growth factor involved in vasodilation, in the dermal papilla, the main cell of hair follicles (Br. J. of Dermatol., 1998; 138; 407-411). In addition to the vasodilation effect of minoxidil in addition to the vasodilation effect, studies have shown that hair follicle cell activation of hair roots in vitro culture (Skin Pharmacol., 1996; 9; 3-8) and hair follicle growth in hair follicle tissue culture (J. Invest) Dermatol., 1989; 92; 315-320) suggest that minoxidil acts as a direct growth factor on the hair root.

In addition, Merck's recently launched propecia, finasteride, inhibits the conversion of androgen testosterone to the more potent form of dihydrotestosterone. In December 1997, a 1 mg tablet was approved for use by FDA in the treatment of androgenetic alopecia, which is currently on the market and has been shown to have a significant clinical effect. However, some male side effects are also reported (J. Am. Acad. Dermatol). , 1998; 39; 578-589). However, this drug, like minoxidil, is not very effective in clinical research, and researches for more excellent hair repellents are being actively conducted due to concerns about side effects.

The inventors searched for various hair growth materials and found that Gossypium nanking Meyen (Mallow and Malvaceae) and cotton seedlings (cotton, cottonseed, Gossypii semen), which are seeds of the same plant, and Gosipol, a component found in various plants, Gossypol) and its derivatives have been found to have excellent hair growth efficacy.

Where R ₁ is COH (aldehyde) and R ₃ , R ₄ are hydrogen.

The present invention is based on the search for hair growth materials for hundreds of natural products, and is a component found in cotton (Gossypium nanking Meyen (Malaceae and Malvaceae)) and seeds of the related plant (cotton, cottonseed, Gossypii semen) and various plants. Gossypol or a derivative thereof finds very good hair growth efficacy and provides a hair growth promoter containing the same.

The present invention has been conducted to study the hair growth efficacy to develop a new hair growth component, as a result of cotton (Gossypium nanking Meyen (Mallow and Malvaceae) and seeds of the same plant, cotton, cottonseed, Gossypii semen and various plant components An object of the present invention is to provide a hair growth promoter containing Gossypol and various synthetic and biosynthetic derivatives thereof as an active ingredient.

Gosipol derivatives of the present invention include the following formulas (1), (2), (3) and other Gosipol derivatives.

In the above formula,

R ₁ is C ₀ -R ₂ or CH = NR ₂ or cyano,

R ₂ is hydrogen. C ₁ -C ₆ straight or branched alkyl, alkenyl, alkynyl, acyl, to which one or more amino, Substituted with hydroxy, halo, haloalkyl, alkoxy, alkoxy, cyano, nitro, alkylamino, dialkylamino, etc. It is included. Here preferably, R ₂ is hydrogen, that is, R ₁ is COH (aldehyde).

R ₃ is hydrogen. C ₁ -C ₆ straight or branched alkyl, alkenyl, alkynyl, acyl, to which one or more amino, Substituted with hydroxy, halo, haloalkyl, alkoxy, alkoxy, cyano, nitro, alkylamino, dialkylamino It is included. Here preferably R ₃ is hydrogen.

R ₄ is hydrogen. C ₁ -C ₆ straight or branched alkyl, alkenyl, alkynyl, acyl, one or more amino, hydroxide Substituted hydroxy, halo, haloalkyl, alkoxy, alkoxy, cyano, nitro, alkylamino, dialkylamino, etc. Included. Preferably R ₄ is hydrogen.

In the above structural formula

R ₄ is as defined in Formula 1

R ₅ is C═O or C = NR ₆ ,

R ₆ is hydrogen. C ₁ -C ₆ straight or branched alkyl, alkenyl, alkynyl, acyl, to which one or more amino, Substituted with hydroxy, halo, haloalkyl, alkoxy, alkoxy, cyano, nitro, alkylamino, dialkylamino It is included

In the above formula,

R ₃ and R ₄ are as defined in Formula 1

R ₇ is composed of C ₁ to C ₁₀ straight carbons, including those in which hydrogen of these carbons is substituted with one or more amino and hydroxy groups.

In addition, the present invention is a hair growth promoter using apogossypol hexaacetate (2,2'-Bi [5-isopropyl-3-methyl-naphthalene-1,6,7-triacetate], which is a gossypol derivative not represented by the above formula. Includes.

In addition, the present invention includes a hair growth promoter having gossypin (3,3 ', 4', 5,7,8-hexahydroxyflavone-8-glucoside) not represented by the above formula as an active ingredient.

In addition, the present invention is a gossypolone (6,6 ', 7,7'-Tetrahydroxy-5,5'-diisopropy-3,3'-dimethyl- [2,2'-binaphthalene] which is a gossypol derivative not represented by the above formula. -1,1 ', 4,4'-tetraone-8,8'-dicarboxyaldehyde), and includes hair growth promoter as an active ingredient.

The present invention provides hair growth promoters wherein the formulation is a liquid, spray, gel, paste, emulsion, cream, conditioner, or shampoo.

Hereinafter, the present invention will be described in detail in Preparation Examples and Preparation Examples.

Preparation Example : Isolation of Gosipoli from Cottonseed Extract

Take 30 g of the powder obtained by pulverizing cottonseed yarn with 20 mesh, add 500 ml of acetone, and extract by immersion for 3 days, filter using No. 1 Whatman No. 1, and concentrate under 40 ° C. 0.7 g of brown cottonseed extract was obtained. In order to separate Gossypol, an active substance, the Gosifol was separated under the following HPLC conditions, and structural analysis was confirmed by Mass and NMR. (C ₁₈ Column, 0.1% H ₃ PO ₄ in MeOH / H ₂ 0 / CHCl ₃ = 70: 30: 40)

Formulation Example 1. Balmotoic

Formulation Examples 1-1 to 1-3. Preparation of Gosipol-containing balmonic

Each of the ingredients in the three formulations shown in Table 1 was mixed and stirred to completely dissolve the balmotonic was prepared. Through the animal evaluation test of Experimental Example 1 below, the hair growth effect of Gosipol-containing balmonic in Table 1 was confirmed.

Raw material name 1-1 1-2 1-3 1. Ethanol 40.0 40.0 40.0 2. Notice 0.1 1.0 10 3. Tocopherol Acetate 0.1 0.1 0.1 4. Salicylic Acid 0.3 0.3 0.3 5. L-menthol 0.3 0.3 0.3 6. Tween 20 0.5 0.5 0.5 7. Spices Quantity Quantity Quantity 8. Pigment Quantity Quantity Quantity 9. Water Add until 100% by weight

Formulation Example 2 Hair Cream

Formulation Examples 2-1 to 2-3: Preparation of Gosipol-Containing Hair Cream

In each of the three formulations shown in Table 2, each of the oily and watery ingredients was separately mixed and heated to 80 ° C to completely dissolve. The prepared oily raw material and the watery raw material of 80 ° C. are mixed and emulsified. After the completion of emulsification, the mixture was cooled to room temperature, and then mixed with fragrance and pigment to prepare hair cream. The amount of water was added to 100% by weight of the sum of the oil and water raw materials.

Through the animal evaluation test of Experimental Example 1 was confirmed the hair growth effect of Gosipol-containing hair cream shown in Table 3.

Raw material name 2-1 2-2 2-3 Paraffin 5.0 5.0 5.0 2. Cetostearyl Alcohol 5.5 5.5 5.5 3. Petrolatum 5.5 5.5 5.5 4. Glycerin Monostearate 3.0 3.0 3.0 5. Polyoxyethylene octyldodecyl ether 3.0 3.0 3.0 6. Propylparaben 0.3 0.3 0.3 7. Notice 0.1 1.0 10 8. Glycerin 7.0 7.0 7.0 9. Dipropylene Glycol 20.0 20.0 20.0 10. Polyethylene Glycol 5.0 5.0 5.0 11.water Add until 1-11 sum is 100% 12. Spices Quantity Quantity Quantity 13. Pigment Quantity Quantity Quantity

Formulation Example 3 Shampoo

Formulation Examples 3-1 to 3-3: Preparation of Gosipol-Containing Shampoo

In the three formulations shown in Table 3, the ingredients, except flavors, pigments, and water, were mixed with each other, mixed with heating, stirred, and completely dissolved. Shampoo was prepared according to 100% by weight.

Raw material name 3-1 3-2 3-3 1.POE sodium lauryl sulfate (30%) 40.0 40.0 40.0 2. Palm oil fatty acid diethanolamide 3.0 3.0 3.0 3. Propylene Glycol 2.0 2.0 2.0 4. Methyl Paraoxybenzoate 0.2 0.2 0.2 5. Ethanol 2.0 2.0 2.0 6. Notice 0.1 1.0 10.0 7. Salicylic Acid 0.3 0.3 0.3 8. L-menthol 0.3 0.3 0.3 9. Spices Quantity Quantity Quantity 10.Color Quantity Quantity Quantity water Add until 100% by weight

Formulation Example 4 Hair Conditioner

Formulation Examples 4-1 to 4-3: Preparation of Gosipol-Containing Hair Conditioner

In each of the three formulations shown in Table 4, each of the oily and watery ingredients was separately mixed and heated to 80 ° C. to completely dissolve. The prepared oily raw material and the watery raw material of 80 ° C. are mixed and emulsified. After the completion of emulsification, the mixture was cooled to room temperature, and then mixed with fragrance and pigment to prepare a hair conditioner. The amount was added to 100% by weight of the sum of the oil and water raw materials.

Raw material name 4-1 4-2 4-3 1. Cetanol 3.0 3.0 3.0 2. Self-emulsifying glycerin monostearate 2.0 2.0 3.0 3. Squalene 10.0 10.0 10.0 4. Notice 0.1 1.0 10.0 5. Propylene Glycol 2.0 2.0 2.0 6. Stearyl Dimethylbenzyl Ammonium Chloride (25%) 8.0 8.0 8.0 7. Methyl Paraoxybenzoate 0.2 0.2 0.2 8. Salicylic Acid 0.3 0.3 0.3 9. L-menthol 0.3 0.3 0.3 10.water Add 100% by weight 11.Fragrance Quantity Quantity Quantity 12.Color Quantity Quantity Quantity

Experimental Example 1

(Examination of hair growth promoting effect of gosipol and gosipolone)

The hair growth promoting test was used 42-49 days old mice (C57BL / 6, female). First, the hair on the back was removed using an electric razor, and each mouse was weighed and divided into several pieces so that the weight was evenly distributed. After the adaptation period for one day, 0.1 micrograms of gosipoul, 0.1 percent gosipolone and rogaine (Rogaine, 5% formulation of minoxidil) were applied to the back of the subject once a day and 100 microliters were applied for 20 days. As a result, the degree of hair growth was visually determined, and the ratio of the area where the newborn hair was grown to the area from which hair was removed was compared.

As shown in Table 5 below, 0.1% of gosypol and 0.1% of gosypolone had a significant hair growth promoting effect compared to the control group applied only vehicle (Rohine, Minoxidil 5% formulation) efficacy Indicated. As a result of comparing the climbing status during the 20-day experiment, no unusual skin irritation was found in the control group and all treatment groups.

matter Effective area% Vehicle 20 Go Seepol 0.1% 96 Giffolon 0.1% 70 Rogaine (5% minoxidil) 45

Applying these results, various formulations such as liquid, spray, gel, paste, emulsion, cream, conditioner and shampoo can be used as preparations containing Gosipol and its derivatives, but commercially used balmonic, hair cream, hair Conditioner, hair shampoo was prepared, and the animal evaluation test of Experimental Example 1 confirmed that the treatment group of the present invention has a superior hair growth effect than the control group.

Hair growth promoters containing Gossypol or derivatives thereof of the present invention exhibit very good hair growth efficacy.

Claims (8)

Hair growth promoter containing Gosipol or Gosipol derivative represented by the following Formula 1 as an active ingredient: [Formula 1] In the above formula, R ₁ is C ₀ -R ₂ or CH = NR ₂ or cyano, R ₂ is hydrogen. C ₁ -C ₆ straight or branched alkyl, alkenyl, alkynyl, acyl, to which one or more amino, Substituted with hydroxy, halo, haloalkyl, alkoxy, alkoxy, cyano, nitro, alkylamino, dialkylamino It is included. Here preferably, R ₂ is hydrogen, that is, R ₁ is COH (aldehyde). R ₃ is hydrogen. C ₁ -C ₆ straight or branched alkyl, alkenyl, alkynyl, acyl, to which one or more amino, Substituted with hydroxy, halo, haloalkyl, alkoxy, alkoxy, cyano, nitro, alkylamino and dialkylamino Included. Here preferably R ₃ is hydrogen. R ₄ is hydrogen. C ₁ -C ₆ straight or branched alkyl, alkenyl, alkynyl, acyl, one or more amino, hydroxide Substituted hydroxy, halo, haloalkyl, alkoxy, alkoxy, cyano, nitro, alkylamino, dialkylamino, etc. Included. Preferably R ₄ is hydrogen. Hair growth promoter containing Gosipol derivative represented by the following formula (2) as an active ingredient [Formula 2] In the above structural formula R ₄ is as defined in Formula 1 R ₅ is C═O or C = NR ₆ , R ₆ is hydrogen. C ₁ -C ₆ straight or branched alkyl, alkenyl, alkynyl, acyl, to which one or more amino, Substituted with hydroxy, halo, haloalkyl, alkoxy, alkoxy, cyano, nitro, alkylamino, dialkylamino It is included. Hair growth promoter containing Gosipol derivative represented by the following formula (3) as an active ingredient [Formula 3] In the above formula, R ₃ and R ₄ are as defined in Formula 1 R ₇ is composed of C ₁ to C ₁₀ straight carbons, and includes those in which the hydrogen of these carbons is substituted with one or more amino and hydroxyl groups. The hair growth promoter according to claim 1, which contains Gossypol as an active ingredient. A hair growth promoter containing apogossypol hexaacetate (2,2'-Bi [5-isopropyl-3-methyl-naphthalene-1,6,7-triacetate]) as an active ingredient. Hair growth promoter containing gossypin (3,3 ', 4', 5,7,8-hexahydroxyflavone-8-glucoside) as an active ingredient Gossypolone (6,6 ', 7,7'-Tetrahydroxy-5,5'-diisopropy-3,3'-dimethyl- [2,2'-binaphthalene] -1,1', 4,4'- Hair growth promoter containing tetraone-8,8'-dicarboxyaldehyde) as an active ingredient 8. The hair growth promoter according to any one of claims 1 to 7, wherein the formulation of the hair growth promoter is liquid, spray, gel, paste, emulsion, cream, conditioner or shampoo.