阅读说明：本技术 一种组合物及其应用 (Composition and application thereof ) 是由 陈晓东 颜凌晨 王旭升 何佳 王婧薷 杨荣华 于 2021-08-31 设计创作，主要内容包括：本发明公开了一种组合物及其应用。所述应用为EGFR激活剂NSC228155在制备外用药物、化妆品或日化用品中的应用,可以解决脱发或毛发稀少的问题。NSC228155在穿过表皮后,能够迅速渗透细胞膜,并在胞质内和细胞核中分散开来,与sEGFR的二聚体化功能域II结合、调节EGFR的酪氨酸磷酸化,激动毛囊中EGFR。EGFR结合后能引起细胞内一系列的生化活动,能刺激表皮和上皮细胞,促进表皮增生和角质化,能强烈的促进细胞——特别是毛囊细胞——分裂,使得毛囊中膨突和毛乳头部位中的干细胞增殖分化,从而令毛囊进入生长期,加快毛发生长,解决脱发或毛发稀少的问题。(The invention discloses a composition and application thereof. The application is the application of an EGFR activator NSC228155 in preparing external medicines, cosmetics or daily chemical products, and can solve the problems of alopecia or hair scarcity. NSC228155, after penetrating the epidermis, rapidly penetrates the cell membrane and disperses in the cytoplasm and the nucleus, binds to the dimerization domain II of the sfegfr, regulates the tyrosine phosphorylation of the EGFR, and stimulates the EGFR in the hair follicle. After EGFR is combined, a series of biochemical activities in cells can be caused, epidermis and epithelial cells can be stimulated, epidermis hyperplasia and keratinization can be promoted, cell division, particularly hair follicle cells, can be strongly promoted, swelling in hair follicles and stem cells in hair papilla parts can be proliferated and differentiated, the hair follicles can enter a growth phase, hair growth is accelerated, and the problem of alopecia or hair scarcity is solved.)

Application of an EGFR activator NSC228155 in preparation of external medicines, cosmetics or daily chemical products.

2. The use according to claim 1, wherein the pharmaceutical, cosmetic or daily chemical product is an external preparation, an implant preparation, an injection preparation or a transdermal preparation.

3. Use according to claim 1, wherein the pharmaceutical, cosmetic or daily chemical product is used for preventing/ameliorating hair loss or hair thinning problems.

4. The use according to claim 3, wherein the hair loss or hair loss comprises androgenic alopecia, alopecia areata process pressure alopecia.

5. The NSC228155 transdermal preparation is characterized in that NSC228155 is mixed with a transdermal enhancer or a transdermal absorption carrier, and the mass concentration of the NSC228155 is 0.001-0.1 mg/L.

6. The NSC228155 transdermal preparation according to claim 5, wherein the transdermal enhancer comprises one or more of thiaketone, azone compound, N-dimethylamino acetate, fatty acid, fatty alcohol, cyclodextrin, terpenes, alcohol compound, borneol, menthol, eucalyptus oil, and ethanol.

7. The NSC228155 transdermal formulation according to claim 6, further comprising a cosolvent, wherein the cosolvent comprises one or more of polyethylene glycol, tween, span, peregal, hydrogenated castor oil.

8. The NSC228155 transdermal formulation according to claim 5, wherein the transdermal absorption carrier comprises one or more of liposome, transfersome, ethosome, and microemulsion.

Technical Field

The invention relates to the technical field of medical preparations, in particular to a composition and application thereof.

Background

Alopecia and sub-health problems with thin hair tend to become increasingly younger, which can seriously affect an individual's mental state and quality of life. Alopecia can be classified into three types according to the theory of cases, the first type is androgenic alopecia (AGA), which is usually seen in young and middle-aged men. The second is alopecia areata, commonly called ghost shaving head, which can occur at any age, but is common in young and strong years, and the incidence rate of both sexes is not obviously different. The third is alopecia due to stress, which is a loss of hair due to mental anxiety or working stress, and can occur at any age. Thinning may be due to the above-mentioned hair loss problems, loss of nutrients to the body, prolonged exposure of the hair to the sun, wind or often a dry environment.

Most of the products related to alopecia in the market are mainly used for preventing alopecia, and only a small part of the products are medicines or external preparations prepared from traditional Chinese medicines such as sesame, fleece-flower root and the like, but the using effect is not obvious.

Disclosure of Invention

The present invention is directed to a composition and its use to solve one or more of the problems of the prior art and to provide at least one useful alternative or creation.

In a first aspect, the invention provides a novel use of the EGFR activator NSC 228155. NSC228155 is generally used in the prior art at the cellular level, and is often used for in vitro cell culture or for pharmaceutical use in treating kidney damage. The inventor surprisingly finds that NSC228155 can be applied to the preparation of external medicines, cosmetics or daily chemical products in the research process to solve the problem of alopecia or hair scarcity. NSC228155, after penetrating the epidermis, rapidly penetrates the cell membrane and disperses in the cytoplasm and the nucleus, binds to the dimerization domain II of the sfegfr, regulates the tyrosine phosphorylation of the EGFR, and stimulates the EGFR in the hair follicle. After EGFR is combined, a series of biochemical activities in cells can be caused, epidermis and epithelial cells can be stimulated, epidermis hyperplasia and keratinization can be promoted, cell division, particularly hair follicle cells, can be strongly promoted, swelling in hair follicles and stem cells in hair papilla parts can be proliferated and differentiated, the hair follicles can enter a growth phase, hair growth is accelerated, and the problem of alopecia or hair scarcity is solved.

Further, the medicine, cosmetic or daily chemical product is an external preparation, an implant preparation, an injection preparation or a transdermal preparation. Since the targeted site of administration is hair follicle cells located in the epithelium, a type of topical agent is needed to help NSC228155 more readily penetrate the epidermis, deep into the epithelial layer.

Further, the pharmaceutical, cosmetic or daily chemical product is used for preventing/improving alopecia or hair thinning problem. The alopecia or hair rarity includes male hormone alopecia and alopecia areata process pressure type alopecia.

The second aspect of the invention provides an NSC228155 transdermal preparation, which comprises the NSC228155 and a transdermal enhancer or a transdermal absorption carrier which are mixed, wherein the mass concentration of the NSC228155 is 0.001-0.1 mg/L.

Further, the transdermal enhancer comprises one or more of thiaketone, azone compounds, N-dimethyl aminoacetic ester, fatty acid, fatty alcohol, cyclodextrin, terpenes, alcohol compounds, Borneolum Syntheticum, menthol, eucalyptus oil, and ethanol.

Further, the NSC228155 transdermal preparation also comprises a cosolvent, wherein the cosolvent comprises one or more of polyethylene glycol, tween, span, peregal and hydrogenated castor oil.

Further, the transdermal absorption carrier comprises one or more of liposome, transfersome, ethosome and microemulsion.

Different from the known application of NSC228155 serving as an EGFR activator, the technical scheme uses NSC228155 to stimulate the division of hair follicle cells in epithelium and directly apply the cell to the hair follicle through a transdermal preparation to promote the proliferation and differentiation of stem cells in the hair follicle bulge and hair papilla part, so as to promote the hair follicle to enter the anagen phase and promote the hair growth.

Drawings

FIG. 1 is an observation image of mice in the test group in example 1;

FIG. 2 is an observation image of a control group mouse in example 1;

FIG. 3 is a histogram of the change in color of the backs of mice in the experimental and control groups.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to specific embodiments, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1 mouse Back Hair irritation test

C57 mice had skin follicles in the back in telogen phase at 7-12 weeks, with the skin pink; when the hair follicle enters the anagen phase, the back skin appears black due to proliferation and secretion of melanin by melanocytes. Therefore, the hair on the back skin of the mouse can be removed after the administration, and the color of the back skin can be observed, so that whether the back skin of the mouse enters the anagen phase and the degree of the back skin entering the anagen phase can be judged.

Preparation of reagents: 0.1mg of EGFR agonist NSC228155 is taken, 100ml of mixed solution of PEG-400 and absolute ethyl alcohol in a volume ratio of 1:1 is taken as a solvent, and NSC228155 working solution is prepared for standby. The blank control was administered with the same mixture of PEG-400 and absolute ethanol as the blank control.

The test steps are as follows:

(1) 10 8 week-old C57 mice were randomly divided into two groups of 5 mice each.

(2) One group of mice was used as a test group and was transdermally administered twice a day, 400. mu.l each time, using NSC228155 working solution. The hair on the back of the mouse is combed by dipping cotton swab in water each time, the skin on the back is exposed, and the working solution is dripped into the skin. Another group of mice served as a control group and blank control was given transdermally twice daily by the same method, 400. mu.l each time.

(3) After 15 days of continuous administration, hair was removed from the backs of the two groups of mice, and changes in the skin on the backs were observed to count the area ratio of the black parts on the backs, respectively. As shown in FIGS. 1 and 2, the average of the skin darkening rate of the back of the test group was 48% and the average of the skin darkening rate of the back of the control group was 10% after 15 consecutive days of administration, respectively. Statistics of the back color changes of two groups of mice are shown in fig. 3, and the experimental group obviously advances into the anagen phase, which shows that the transdermal preparation prepared from NSC228155 can advance the hair into the anagen phase and promote the hair growth.

It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.