Application of ruscogenin in preparation of products for preventing and / or treating alopecia

Abstract

The invention discloses application of ruscogenin in preparation of products for preventing and / or treating alopecia, and belongs to the technical field of medicines. The invention finds that ruscogenin can inhibit the activity of 5alpha-reductase, inhibit death of human dermal hair follicle nipple cells caused by dihydrotestosterone, promote proliferation of the human dermal hair follicle nipple cells and promote hair growth. The ruscogenin can be applied to preparation of products for preventing and / or treating alopecia, new application of the ruscogenin is provided, and a new choice is provided for preventing and treating alopecia.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine, and particularly relates to application of ruscogenin in preparation of a product for preventing and / or treating alopecia. BACKGROUND

[0002] Alopecia is a disease characterized by hair loss, reduction in number and density, and is prone to cause a series of physiological or psychological health problems. It is reported that alopecia affects more than 50% of the global population, and has become a problem to be solved urgently.

[0003] Androgenetic alopecia (AGA) is the most common type of alopecia, affecting about 50% of men and 20% of women worldwide. Its pathogenesis is mainly related to the following factors: 5-alpha-reductase in the hair follicle converts testosterone into more active dihydrotestosterone (DHT); dihydrotestosterone (DHT) binds to androgen receptor (AR), leading to miniaturization of hair follicles; inflammation around the hair follicle exacerbates hair follicle degeneration. The current main clinical treatment drugs, finasteride and minoxidil, have obvious limitations: finasteride can cause sexual dysfunction (incidence rate of about 2%-4%); minoxidil has strong local irritation, and has a high recurrence rate after drug withdrawal.

[0004] Ruscogenin is a steroidal saponin extracted from the traditional Chinese medicine Ophiopogon japonicus, which has anti-inflammatory, antioxidant and pro-angiogenic activities. Recent studies have found that it can significantly inhibit the NF-kappa B inflammatory pathway and promote angiogenesis by regulating VEGF. However, as of now, there has been no report on the application of ruscogenin in the treatment of alopecia. SUMMARY

[0005] In view of the problems in the prior art, the application provides the application of ruscogenin in the preparation of a product for preventing and / or treating alopecia. The application first found that ruscogenin can effectively improve androgenetic alopecia (AGA) and promote hair growth through a multi-target mechanism, which has important clinical application value.

[0006] The object of the application is achieved by the following technical solutions: Firstly, the application provides the application of ruscogenin or a pharmaceutically acceptable salt thereof in the preparation of a product for preventing and / or treating alopecia.

[0007] Ruscogenin is a natural steroidal saponin, also known as spirocolojin in Chinese and Ruscogenin in English, with the English alias (25R)-spirost-5-ene-1-beta,3-beta-diol, the CAS number 472-11-7, the molecular formula C 27 H 42 O4.

[0008] Preferably, the alopecia is androgenetic alopecia and / or senescent alopecia.

[0009] Preferably, the product can promote the proliferation of human dermal hair follicle papilla cells and promote hair growth.

[0010] Preferably, the product inhibits the death of human dermal hair follicle papilla cells caused by dihydrotestosterone.

[0011] Preferably, the product inhibits 5 -reductase activity.

[0012] Preferably, the product is a medicine or a care product.

[0013] Preferably, the medicine further comprises a pharmaceutically acceptable pharmaceutical excipient.

[0014] Preferably, the pharmaceutically acceptable excipient comprises any one of a sustained-release agent, an excipient, a filler, a binder, a humectant, a disintegrant, an absorption enhancer, a surfactant, a lubricant, or a combination of at least two of them, such as a combination of a binder and an excipient, a combination of a binder and a flavoring agent, a combination of a binder and a filler, and the like, and any other combination can be selected, which will not be described one by one here.

[0015] Preferably, the pharmaceutical dosage form is a tablet, a capsule, a granule, an injection, an oral liquid, a pill, a paste, a suspension, a dispersion, a syrup, a suppository, a gel, an aerosol or a patch.

[0016] Preferably, the care product is selected from a shampoo, a hair conditioner, a hair serum, a hair oil, a hair cream, a scalp paste, a hair gel, a hair spray, a hair mask or an eyebrow care solution.

[0017] The present application also provides a pharmaceutical combination for preventing or / and treating alopecia, comprising ruscogenin or a pharmaceutically acceptable salt thereof and a pharmaceutical excipient that can be used in alopecia medicine.

[0018] Beneficial effects: The present application provides a new use of ruscogenin, which is first found to effectively improve alopecia and promote hair growth through a multi-target mechanism, and can be used for preparing a medicine or a care product for preventing and / or treating alopecia, thereby providing a new choice for preventing and treating alopecia.

[0019] Rusco genin is a natural steroidal saponin, which is widely present in ophiopogon japonicus, ruscus aculeatus and the like. As a medicine for preventing and treating androgenetic alopecia, ruscogenin has the characteristics of wide source, green safety and mild action condition compared with the existing positive drugs minoxidil and finasteride on the market, thereby greatly reducing the side effects of androgenetic alopecia treatment drugs.

[0020] Ruscogenin can improve androgenic alopecia and promote hair growth by inhibiting 5α-reductase activity, inhibiting dihydrotestosterone-induced human dermal papilla cell death, promoting the proliferation of human dermal papilla cells and other multi-target effects. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 Figure for evaluation of the effect of ruscogenin on inhibiting 5α-reductase activity; Figure 2 Figure for the results of cytotoxicity experiment of ruscogenin on the growth of human dermal papilla cells (HDPCs); Figure 3 Figure for the results of the influence of ruscogenin on DHT-induced human dermal papilla cell androgenic alopecia pathological model; Figure 4 Figure for the results of the treatment effect of ruscogenin on androgenic alopecia (AGA) in C57BL6 mice. DETAILED DESCRIPTION

[0022] The present application will be further described in detail below in conjunction with the accompanying drawings and examples, but in no way limits the present application, and any transformation or improvement based on the teaching of the present application falls within the protection scope of the present application.

[0023] The process, conditions, reagents, experimental methods, etc. for implementing the present application, except for the following specifically mentioned contents, are the general knowledge and common sense in the art, and the present application has no special limitation. The experimental methods not specified in the specific conditions in each example are usually carried out according to the conventional conditions or according to the conditions suggested by the manufacturer.

[0024] The following are the sources of some main reagents and consumables in the examples: Ruscogenin was purchased from Chengdu Zhishanghua Pure Biotechnology Co., Ltd.; Human dermal papilla cells (HDPCs) were purchased from Sibiongen (Shanghai) Biotechnology Co., Ltd.; C57BL / 6 mice were purchased from Yunnan University; Finasteride was purchased from Beijing Solabio Technology Co., Ltd.; Testosterone was purchased from Shanghai Jizhisheng Biochemical Technology Co., Ltd.; 5α-reductase was extracted from the liver of SD rats; Reduced coenzyme II tetrasodium was purchased from Beijing Solabio Technology Co., Ltd.

[0025] Example 1 Evaluation of the effect of inhibiting 5α-reductase activity Experimental grouping: the experiment is divided into three groups: blank control group, finasteride group and drug group; among them, the blank control group is testosterone, 5α-reductase, reduced coenzyme II tetrasodium, pure water; the finasteride group is finasteride solution, testosterone, 5α-reductase, reduced coenzyme II tetrasodium, pure water; the drug group is lusokogenin, testosterone, 5α-reductase, reduced coenzyme II tetrasodium, pure water.

[0026] The reaction systems of the above groups were incubated at 37°C, and the time change curve of the characteristic absorption wavelength OD value of NADPH (reduced coenzyme II tetrasodium) was continuously measured at 340 nm by ultraviolet grating spectrophotometer. According to the NADPH (reduced coenzyme II tetrasodium) standard curve, the concentration reduction rate of NADPH (reduced coenzyme II tetrasodium) as an enzymatic reaction substrate within 10 min was calculated, and the reduction rate of the blank test tube was deducted, that is, the enzyme activity, and the average value of three groups in parallel was taken.

[0027] The determination results are shown in Figure 1 , and the results show that the lusokogenin of the application has obvious inhibitory effect on the activity of 5α-reductase.

[0028] Example 2: Effect of in vitro experiment on hair papilla cells 1. Preparation of lusokogenin mother liquor Prepare 100 mg / mL lusokogenin mother liquor: weigh lusokogenin powder with an electronic balance, and prepare a mother liquor with a concentration of 100 mg / mL using dimethyl sulfoxide (DMSO), and then dilute it with DMSO to different concentrations.

[0029] 2. Cytotoxicity experiment of lusokogenin on hair follicle dermal papilla cells Human hair follicle dermal papilla cells (HDPCs) were trypsinized and seeded into 96-well plates at 1×10 5 per well, incubated at 37°C overnight, and then the final concentration of 0 μg / mL, 15.63 μg / mL, 31.25 μg / mL, 62.5 μg / mL, 125 μg / mL, and 250 μg / mL of lusokogenin was added to the corresponding culture dishes, and the cell viability was determined by CCK-8 method after 24 hours of incubation at 37°C. Then, the fitting curve of drug concentration corresponding to cell survival rate was drawn by GraphPad Prism8.

[0030] The results are shown in Figure 2 As can be seen from the figure, lusokogenin has less toxicity to human hair follicle dermal papilla cells (HDPCs).

[0031] 3. Effect of lusokogenin on DHT-induced androgenetic alopecia pathological model of human hair follicle dermal papilla cells Dihydrotestosterone (DHT) was dissolved in DMSO to a 100 mg / mL stock solution, which was then diluted with culture medium to obtain 31.25 μg / mL DHT. This was then used to culture human hair follicle dermal papilla cells (HDPCs) as a model. The intervention group received 31.25 μg / mL DHT and 62.5 μg / mL, 125 μg / mL, or 250 μg / mL of ruscogenin, respectively. The control group received untreated standard culture medium. Cell viability was determined using the CCK-8 assay after 24 hours of culture.

[0032] The results are as follows Figure 3 As shown, the results showed that ruscosapogenin had a certain effect on promoting the proliferation of hair papilla cells after modeling, indicating that ruscosapogenin could inhibit the death of human dermal hair follicle papilla cells induced by dihydrotestosterone and promote proliferation.

[0033] Example 3 Experiment on the Effect of Ruscogenin on C57BL / 6 Mouse Alopecia Model In order to verify the effect of ruscosapogenin on promoting hair growth in vivo, the present invention selected C57BL / 6 mice for in vivo efficacy verification. The specific experimental method is as follows: Thirty 18-month-old C57BL / 6 mice were selected and divided into three groups: an elderly group (model group), a low-dose ruscosapogenin group, and a high-dose ruscosapogenin group. Drugs were administered via feed: the elderly group received a normal diet, the low-dose group received a diet containing 75 mg / kg ruscosapogenin, and the high-dose group received a diet containing 150 mg / kg ruscosapogenin. The mice were fed for three months and their coat color, mobility, and mental state were observed. Two-month-old young C57BL / 6 mice served as controls. Hair growth was photographed and recorded in each group. The results are as follows Figure 4 As shown in the figure, it can be seen that ruscosaponin has a certain therapeutic effect on aging-related hair loss, and the high-dose ruscosaponin is more effective than the low-dose and has fewer side effects.

[0034] Unless otherwise specified, the meanings of all professional terms and scientific terms used in this specification are the same as those generally understood by those skilled in the art to which the present invention belongs. However, in the event of any conflict, the present specification including the definitions shall prevail. Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, not to limit them. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. Use of ruscosapogenin or a pharmaceutically acceptable salt thereof in preparing a product for preventing and / or treating hair loss.

2. The application according to claim 1, characterized in that The hair loss is androgenic alopecia and / or senile alopecia.

3. The application according to claim 1, characterized in that The product can promote the proliferation of human dermal hair follicle papilla cells and promote hair growth.

4. The application according to claim 1, characterized in that The product inhibits dihydrotestosterone-induced cell death in human dermal follicle papilla cells.

5. The application according to claim 1, characterized in that: The product inhibits 5α-reductase activity.

6. The application according to claim 1, characterized in that: The product is a medicine or a toiletries.

7. The application according to claim 6, characterized in that The medicine also includes pharmaceutically acceptable excipients.

8. The application according to claim 7, characterized in that: The pharmaceutical dosage form is tablets, capsules, granules, injections, oral liquids, pills, ointments, suspensions, dispersions, syrups, suppositories, gels, aerosols or patches.

9. The use according to claim 6, characterized in that The cleaning products are selected from shampoo, hair conditioner, hair essence, hair oil, hair lotion, scalp cream, hair gel, hair spray, hair mask or eyebrow care solution.

10. A pharmaceutical composition for preventing and / or treating hair loss, comprising ruscosapogenin or a pharmaceutically acceptable salt thereof and a pharmaceutical excipient that can be used in a hair loss treatment drug.

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