KR20130134881A - Composition for inhibiting hair growth - Google Patents

Abstract

The present invention relates to a pharmaceutical composition and a cosmetic composition containing peiminine, dihydromollugin, chrysophanol, or a mixture thereof as active ingredients for inhibiting hair growth, a method for inhibiting hair growth, a composition for promoting the production of epidermal growth factor (hEGF), and a method for increasing the production of hEGF. The composition for inhibiting hair growth in the present invention overcomes weaknesses in problems with the conventional chemical and physical depilatories and disability by the use of hEGF itself and inhibits the growth of facial hair or body hair, thereby being widely used for developing more effectual skin care products. [Reference numerals] (AA) Comparison group;(BB) Experimental group 1;(CC) Experimental group 2;(DD) Experimental group 3

Description

[Composition for inhibiting hair growth]

The present invention relates to a composition for inhibiting hair growth, and more specifically, the present invention relates to a pharmaceutical composition for inhibiting hair growth, which comprises as an active ingredient pemimeline, dihydromorpholin, crysopanol or a combination thereof, Compositions, methods for inhibiting hair growth, compositions for promoting the production of epithelial growth factors, and methods for increasing the production of human epithelial cell growth factors.

Animal hair or body hair has been developed as one of the important defenses of the body that protects the organs of the body from external stimuli. However, in the case of humans, the body hair, except for the hair, plays a role as a defensive means. In particular, when viewed from an aesthetic point of view, it is desirable for women to have no hairs in the opposite direction, and accordingly, various methods are used to remove hairs. Examples of methods for removing hairs include a method of removing hair from hair using a mechanical means such as an electric shaver, an epilator, an ultrasonic wave, and a laser, a method of using a physical means such as an adhesive tape, a hair removal cream , A wax, a gel, or the like is used as a hair removal method. However, when mechanical or physical means are used, there is a disadvantage that it involves a considerable level of pain. When chemical means are used, it is accompanied by pain, In order to overcome these drawbacks, various studies have been carried out.

On the other hand, epidermal growth factor (hEGF) is composed of 53 amino acids and 6 cysteines are three disulfide bond proteins. Although the epithelial growth factor acts on various tissues, it is known to play an important role in the wound healing process, in particular, in regulating cell proliferation, migration, binding, and inflammation of skin. These epithelial growth factors are known to decrease the expression amount as the aging progresses, thereby decreasing the proliferation and migration of the skin cells, which may cause skin aging, skin wrinkles and elasticity degradation, inhibiting hair follicle development And it is known to cause the action of delaying the hair cycle (Cohen and Elliott et al., 1963, J. Invest. Dermatol, 40: 1-5, Kashiwagi, and Huh, N., 1997, , 189: 22-32, Gavin D. and Colin AB Jahoda., 2009, Development., 136: 2153-2164). Accordingly, research has been conducted to develop drugs or functional cosmetics using the epithelial growth factor itself as a raw material for cosmetics or skin external application, but since the epithelial growth factor is not stable at room temperature as well as being expensive, Is short.

Under these circumstances, the inventors of the present invention have found that it is possible to safely protect the human body and effectively inhibit facial or hair growth by taking into account the disadvantages of hair removal agents by conventional chemical and physical means and instability due to the self-use of epithelial growth factors As a result of intensive researches to provide a composition for promoting epithelial cell growth factor production, it has been found that when peiminine, dihydromolugin or chrysophanol is used, And the hair growth can be effectively inhibited safely, and the present invention has been completed.

It is an object of the present invention to provide a pharmaceutical composition for inhibiting hair growth.

Another object of the present invention is to provide a cosmetic composition for inhibiting hair growth.

It is still another object of the present invention to provide a method for inhibiting hair growth by using the cosmetic composition.

It is still another object of the present invention to provide a composition for promoting the production of epithelial cell growth factor.

It is still another object of the present invention to provide a method for increasing the production of human epithelial cell growth factor using the composition for promoting the production of epithelial growth factor.

According to one embodiment of the present invention, the present invention provides a method for producing an epitope comprising peiminine, dihydromolugin, chrysophanol, or a combination thereof as an active ingredient And a composition for promoting the production of a cell growth factor.

The term "peiminine" of the present invention means a compound represented by the following general formula (1), which can be isolated from a natural source, but is not limited thereto and can be chemically synthesized by a method known in the art, Can be used. For the purpose of the present invention, the pemiminin can be used as a component capable of promoting the production of epithelial growth factor from the skin, and can be used for inhibiting hair growth.

The term "dihydromolugin " of the present invention means a compound represented by the following formula (2), which can be isolated from a natural source, but is not limited thereto, and may be chemically synthesized by a method known in the art, Commercially available materials can be used. For the purpose of the present invention, the dihydromolughin can be used as an ingredient capable of promoting the production of epithelial growth factor from the skin and can be used for inhibiting hair growth.

The term "Chrysophanol " of the present invention means an anthraquinone-based compound represented by the following formula (3), which can be isolated from a natural source, but is not limited thereto and may be chemically Synthesized, or commercially available materials. For the purpose of the present invention, the above-mentioned creosopherol can be used as a component capable of promoting the production of epithelial growth factor from the skin, and can be used for inhibiting hair growth.

Each of the compounds contained in the composition may be in the form of a solvate, a pro-drug or a pharmaceutically acceptable salt thereof, and the solvate may preferably include hydrates and ethanolates.

In addition, the composition of the present invention may further comprise a pharmaceutically acceptable carrier. The composition comprising a pharmaceutically acceptable carrier may be of various parenteral formulations. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used. Such preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like. The pharmaceutical composition may be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories It can have one formulation.

The term "promoting the production of epithelial cell growth factor" in the present invention means a process of increasing the amount of protein produced by increasing the expression of intracellular epithelial cell growth factor gene including skin cells. When the production of intracellular epithelial growth factors including skin cells is promoted, intracellular signal transduction occurs by binding epithelial growth factors to the epithelial growth factor receptor present on the cell surface, and as a result, various biochemical changes Epithelial cell growth factor receptor, and the like. Ultimately, DNA synthesis and cell growth progress. For the purpose of the present invention, the promotion of the production of the epithelial growth factor may be used as an intermediate process for inhibiting hair growth, but is not particularly limited thereto.

The term "hairs" of the present invention is used as a meaning including all kinds of hairs growing on the epidermis of an animal, including hairs growing on the scalp.

The term "hair growth inhibition" of the present invention can also be used with the same meaning as "hair growth inhibition ".

According to one embodiment of the present invention, it can be seen that the activity of the promoter of human epithelial cell growth factor and the production of human epithelial cell growth factor can be increased by pemimin, crysopanol or dihydrodimorpholine (Figs. 2 and 3).

The composition can be used as a component of a facial or hair growth inhibitory dermatological external agent. In addition, the composition of the present invention can be used as a component of an external preparation for skin for preventing skin aging through improvement of skin elasticity, wrinkles of skin, moisturizing and the like, and can be used as a component of a skin external preparation for scarring such as burns and acne, But can be used for the improvement of other diseases or conditions in which human epithelial cell growth factors are required.

According to another aspect of the present invention for achieving the object of the present invention, there is provided a pharmaceutical composition for inhibiting hair growth comprising peymenin, dihydromorpholin, crysopanol, or a combination thereof.

The pharmaceutical composition for inhibiting hair growth according to the present invention utilizes the characteristics of the epithelial growth factor which inhibits follicular development and delays hair cycle and is administered with a composition containing the compound exhibiting the effect of promoting the production of epithelial growth factor Promotes the production of epithelial cell growth factors in skin cells, inhibits hair follicle development by delaying the hair cycle by the epithelial growth factor produced thereby, and consequently has an effect of inhibiting hair growth.

The composition may further comprise a pharmaceutically acceptable carrier and may be formulated. When the composition is formulated, it may be prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient. For the purpose of the invention, the composition may be formulated into preparations for parenteral administration in general, including sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like. The pharmaceutical composition may be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories It can have one formulation.

In another aspect, the composition of the present invention may be administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" of the present invention means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is determined by the kind and severity of the subject, age, sex, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by a person skilled in the art.

The term "administering" in the present invention means introducing the composition of the present invention by any appropriate method, and the administration route of the composition of the present invention can be administered through any ordinary route as long as it can reach the target tissue. Preferably, transdermal administration can be carried out, and local application is most preferable. The number of times application of the composition of the present invention can be determined depending on the prescription, necessity or desire. The composition of the present invention may be prescribed in parallel with a surgical method such as a laser. It can also be incorporated into casts, bandages, dressings, gauze pads, and similar items.

According to another aspect of the present invention for achieving the object of the present invention, there is provided a cosmetic composition for inhibiting hair growth comprising peymenin, dihydromorpholin, crysopanol, or a combination thereof.

The cosmetic composition can be used for the production of functional cosmetics for hair growth inhibition.

The term "cosmedical, cosmeceutical" of the present invention refers to a product having a professional function that has a physiologically active effect and an effect emphasized, unlike general cosmetics, A product that helps, a product that helps to improve wrinkles, a product that helps protect skin from burns or UV rays. For the purpose of the present invention, the functional cosmetic product may be a product exhibiting a hair growth inhibitory effect, wherein the content of the peymenin, dihydromorpholine, crysopanol, or a combination thereof contained in the functional cosmetic product is Is preferably from 0.0005 to 5% by weight, more preferably from 0.001 to 3% by weight, and most preferably from 0.01 to 1% by weight. When the content is less than 0.0005% by weight, the effect is too weak. When the content is more than 5% by weight, the effect of the increase of the content is insignificant And the stability of the shape is not ensured.

The functional cosmetic composition of the present invention may be prepared in any form conventionally produced in the art and may be in the form of a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, , Oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, the present invention relates to a cosmetic lotion for cosmetic lotion, cosmetic lotion, convergent lotion, nutritional lotion, nutritional cream, massage cream, lotion, gel, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, ointment, stick, May be prepared in a formulation.

According to one embodiment of the present invention, an essence, which is a kind of cosmetic material including peymenin, chrysopanol, or dihydrodimorpholine, is prepared (Example 3-1), and the hair growth inhibitory effect As a result, it was confirmed that the material for promoting the production of epithelial cell growth factor could inhibit hair growth (FIGS. 4 and 4).

According to another embodiment of the present invention, there is provided a method for inhibiting hair growth, comprising applying the composition for inhibiting hair growth to a skin of a desired individual.

According to another aspect of the present invention, there is provided a method for increasing the production of human epithelial cell growth factor comprising the step of treating cells with a composition for promoting the production of epithelial growth factor to provide.

The composition for inhibiting hair growth of the present invention overcomes the disadvantages of hair removal agents by conventional chemical and physical means and instability caused by self-use of epithelial growth factors, thereby effectively inhibiting facial or hair growth It can be widely used to develop more effective skin beauty products.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic diagram showing genes of the human epithelial cell growth factor (hEGF) promoter region contained in the cloned reporter vector.
FIG. 2 is a graph showing the change in the degree of activation of the human epithelial cell growth factor promoter according to the treatment with pemiminin, crysopanol or dihydromorpholin, wherein sample 1 represents pemiminin and sample 2 represents creosote And sample 3 represents dihydromorpholine.
FIG. 3 is a graph showing the change in the expression level of human epithelial cell growth factor according to the treatment of pemiminin, crysopanol or dihydromorpholin, wherein sample 1 represents a pemiminin and sample 2 represents a crysopanol , And sample 3 represents dihydromorpholine.
4 is a photograph showing the hair growth inhibitory effect of the composition for inhibiting hair growth of the present invention.

Hereinafter, the constitution and effects of the present invention will be described in more detail through examples. These embodiments are only for illustrating the present invention, and the scope of the present invention is not limited by these embodiments.

In the following Experimental Examples and Examples of the present invention, Sample 1 refers to Peiminine, Sample 2 refers to Chrysophanol, and Sample 3 refers to Dihydromollugin, (Shaanxi Shipyang Bio Co., Ltd.).

Example 1 Effect of Peiminine, Chrysophanol or Dihydromollugin on the Promoter Activity of Human Epithelial Cell Growth Factor

The effect of peiminine, chrysophanol and dihydromolugin on the promoter activity of human epithelial cell growth factor was investigated.

Reporter vectors were prepared for this purpose. Specifically, the promoter region was amplified by performing PCR using the following primers with the promoter region (-890 to +80) of the human epithelial cell growth factor present in the human genomic DNA as a template (94 ° C for 1 minute 56 < 0 > C for 45 seconds and 72 < 0 > C for 45 seconds; 30 cycles).

Forward primer: 5'-CGGGGTACCCCCATCGTGCATCAAATCTGCTAT-3 '(SEQ ID NO: 1)

Reverse primer: 5'-ATCCAAGGGTTGTAGCTGGAACTCCATGGCATG-3 '(SEQ ID NO: 2)

The amplified promoter region was digested with restriction enzymes KpnI and NcoI and inserted into a pGL3 vector expressing luciferase to prepare a reporter vector (Fig. 1). BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic diagram showing genes of the human epithelial cell growth factor (hEGF) promoter region contained in the cloned reporter vector.

Meanwhile, the prepared expression vector was introduced into human fibroblasts cultured in DMEM medium containing 10% fetal bovine serum (FBS) for 18 hours by the method using lipofectamine to obtain a transformant And the transformant was cultured for 5 hours. After completion of the cultivation, the transformant was washed twice with DMEM medium not containing FBS, and each sample of pemiminin, crysopanol or dihydrodimorpholine was contained at 5 ppm or 20 ppm, and FBS Lt; RTI ID = 0.0 > DMEM < / RTI > After the incubation was completed, the cells were washed with PBS, and the cells were lysed by adding a cell lysis buffer, which was then centrifuged to obtain a supernatant. Luciferase analysis was performed on the obtained supernatant, and the fluorescence value was measured (FIG. 2, Table 1). At this time, as the control group, a transformant cultured without treatment with pemimin, crysopanol or dihydrodimorpholine was used.

FIG. 2 is a graph showing changes in the degree of activation of the human epithelial cell growth factor promoter following treatment with pemiminin, crysopanol, or dihydromorpholin, wherein sample 1 shows a pemiminin and sample 2 shows Cresopanol, and sample 3 represents dihydromorpholine.

Name of sample Increase Control group
Sample 1 5 ppm
Sample 1 20 ppm
Sample 2 5 ppm
Sample 2 20 ppm
Sample 3 5 ppm
Sample 3 20 ppm 100%
112%
139%
120%
156%
122%
157%

As shown in FIG. 2 and Table 1, it can be seen that the activity of the promoter of human epithelial cell growth factor can be increased by the use of pemiminin, crysopanol, or dihydrodimorpholine, , The activity of the promoter was increased. In addition, it was confirmed that the increase level of the activity of the promoter increased to the highest level of dihydromorpholine, and that the activity of the promoter could be increased in the order of crysopanol and peymenin.

Example 2: Promoting the production of human epithelial cell growth factor by pemiminin, crysopanol, or dihydromololgin

Human fibroblasts cultured in DMEM medium containing 10% FBS for 18 hours were washed twice with DMEM medium not containing FBS, and each sample of pemiminin, crysopanol or dihydromorpholine was diluted to 5 ppm or And cultured in DMEM medium containing no FBS for 18 hours. After completion of cultivation, the concentration of epithelial growth factor secreted into the culture medium was measured by ELISA method and compared with each other (FIG. 3 and Table 2). At this time, as a control group, human fibroblasts cultured without treatment with pemimin, crysopanol, or dihydrodimorpholine were used.

FIG. 3 is a graph showing the change in the expression level of human epithelial cell growth factor according to the treatment of pemiminin, crysopanol or dihydromorpholin, wherein sample 1 represents a pemiminin and sample 2 represents a crysopanol , And sample 3 represents dihydromorpholine.

Name of sample Increase Control group
Sample 1 5 ppm
Sample 1 20 ppm
Sample 2 5 ppm
Sample 2 20 ppm
Sample 3 5 ppm
Sample 3 20 ppm 100%
117%
152%
160%
202%
136%
181%

As shown in FIG. 3 and Table 2 above, it can be seen that the amount of the epithelial growth factor can be increased by the use of pemimin, crysopanol, or dihydrodimorpholine, and the treatment of the pemiminin, crysopanol or dihydromorpholine It was found that the activity of the promoter was increased in proportion to the concentration. In addition, it was confirmed that the increased level of the activity of the promoter was increased to the highest level of crysopolol, and the secretion amount of the epithelial growth factor could be increased in the order of dihydromorpholine and peymenin.

Example 3 Effect of Peymanin, Chrysopanol or Dihydromorpholine on Hair Growth Inhibitory Effect

Example 3-1: Preparation of a cosmetic comprising peymenin, crysopanol or dihydromorpholine

An essence was prepared by adding each of the components listed in Table 3 below and adding pemiminin, crysopanol, or dihydrodimorpholine as active ingredients. In the comparative group, the essence was prepared by adding the components and contents described in the following Table 3 without adding the sample.

Essences containing substances for promoting epithelial growth factor production (Unit: wt%) Experiment 1 Experiment 2 Experiment group 3 Comparative group Pemiminin
Crisopapol
Dihydro morpholine
Propylene glycol
glycerin
Sodium hyaluronate aqueous solution (1%)
ethanol
Polyoxyethylene hardened castor oil
Methyl paraoxybenzoate
incense
Purified water 0.5
-
-
10.0
10.0
5.0
5.0
1.0
0.1
Suitable amount
To 100 -
0.5
-
10.0
10.0
5.0
5.0
1.0
0.1
Suitable amount
To 100 -
-
0.5
10.0
10.0
5.0
5.0
1.0
0.1
Suitable amount
To 100 -
-
-
10.0
10.0
5.0
5.0
1.0
0.1
Suitable amount
To 100

Example 3-2: Confirmation effect of hair growth inhibition by C57BL / 6 mouse

Evaluation of Inhibition of Hair Growth In the animal test, 42-56 day-old mice (C57BL / 6, female, BioLink) were used. First, hair on the back was removed using an electric razor, and each mouse was weighed and divided into six so that the weight was evenly dispersed. From the next day after epilating, the prescription of the comparative group was applied as a control group among the respective essences prepared in Example 3-1, and the prescriptions of the test groups 1 to 3 were applied once a day for 100 days to the test group for 35 days. After 35 days, the weight of the newly produced hair at the epilated area was measured and compared (Table 4 and Figure 4). 4 is a photograph showing the hair growth inhibitory effect of the composition for inhibiting hair growth of the present invention.

Inhibition of hair growth by substances for promoting epithelial cell growth factor production Experimental group Weight of hair (mg) Comparative group
Experiment 1
Experiment 2
Experiment group 3 15.6
10.6
3.4
2.3

4, and 4, it can be seen that the growth of hairs can be inhibited by pemimin, crysopanol, or dihydrodimorpholine, and in particular, dihydroimolginine inhibits hair growth by about 15% , And it was confirmed that the content of crysopanol was lowered to about 22% and that of peymenin was lowered to about 68% or lower.

In addition, no adverse effects occurred in the epilated skin area of the mouse.

<110> LG HOUSEHOLD & HEALTH CARE LTD. <120> Composition for inhibiting hair growth <130> PA110980 / KR <160> 2 <170> Kopatentin 2.0 <210> 1 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 1 cggggtaccc ccatcgtgca tcaaatctgc tat 33 <210> 2 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 2 atccaagggt tgtagctgga actccatggc atg 33

Claims (9)

A pharmaceutical composition for inhibiting hair growth comprising peiminine, dihydromollugin, chrysophanol or a combination thereof as an active ingredient.
The method of claim 1,
Lt; RTI ID = 0.0 &gt; pharmaceutically &lt; / RTI &gt; acceptable carrier.
A cosmetic composition for inhibiting hair growth, including feminine, dihydromolugin, chrysopanol or a combination thereof.
The method of claim 3,
Wherein the composition has a formulation of an external preparation for skin.
5. The method of claim 4,
Wherein the external preparation for skin is ointment, lotion, essence, lotion, cream, pack, gel, ointment, patch or spray.
The method of claim 3,
Wherein the composition comprises 0. &lt; RTI ID = 0.0 &gt; 5O5% &lt; / RTI &gt; by weight of the total composition of the composition.
A method of inhibiting growth of hair, comprising applying the composition of any one of claims 3 to 6 to the skin of an individual in need of hair growth inhibition.
A composition for promoting the production of epidermal growth factor, including peminin, dihydromollugin, chrysophanol, or a combination thereof.
A method of increasing the production of human epidermal growth factor comprising treating a cell with the composition of claim 8.

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