Application of teicoplanin in the preparation of a medicament for treating androgenetic alopecia

Abstract

The present invention discloses the use of teicoplanin in the preparation of a medicament for treating androgenetic alopecia. The teicoplanin of the present invention can effectively promote hair growth in the androgenetic alopecia area, inhibit the expression of androgen receptors, and promote the proliferation of dermal papilla cells. Compared with the existing medicaments for treating androgenetic alopecia, it has fewer side effects and faster effects. Moreover, the teicoplanin selected in the present invention is a medicament already approved for clinical use, with few side effects, a safe medication method, a wide source of the drug, and a simple and economical acquisition method.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and particularly relates to the application of teicoplanin in the preparation of a medicament for treating androgenetic alopecia. Background Art

[0002] Androgenetic alopecia (AGA), as one of the most common types of alopecia, mostly occurs in young adults with strong sebaceous gland secretion, and is closely related to the levels of dihydrotestosterone (DHT) and androgen receptor (AR) in the human body. DHT can cause the hair follicles to gradually atrophy, shorten the hair growth cycle, and thus trigger the process of AGA. The clinically commonly used drugs for treating AGA, minoxidil and finasteride, both require long-term and continuous use to take effect. Finasteride can cause changes in body hormones and easily lead to sexual dysfunction in male patients; the commonly reported side effects of the other drug, minoxidil, are mainly local hirsutism, skin irritation erythema, etc. AGA is characterized by repeated attacks and is difficult to cure, and there is currently no drug that can cure it.

[0003] Teicoplanin is a glycopeptide antibiotic of the vancomycin family, an antibiotic mixture composed of multiple compounds with very similar chemical structures. Teicoplanin is currently mainly used for the treatment of severe infections caused by sensitive bacteria such as Staphylococcus aureus and Streptococcus, and also has an effect on infections of the skin, soft tissues, etc. In addition, it has low toxicity and side effects, high safety when used in combination with other antibiotics, and a long post-antibiotic effect. Therefore, teicoplanin is conducive to outpatient treatment and is acceptable to patients. Currently, teicoplanin for injection is mainly used clinically, and there is no report on the use of teicoplanin for the treatment of AGA. Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the above prior art. For this purpose, the present invention provides the application of teicoplanin in the preparation of a medicament for treating androgenetic alopecia.

[0005] The present invention also provides a medicament for treating androgenetic alopecia.

[0006] According to the first aspect of the present invention, there is provided the application of teicoplanin in the preparation of a medicament for treating androgenetic alopecia.

[0007] In some embodiments of the present invention, the androgenetic alopecia is androgenetic alopecia caused by testosterone.

[0008] In some embodiments of the present invention, the medicament for treating androgenetic alopecia is a medicament for promoting hair growth in the area of androgenetic alopecia.

[0009] In some embodiments of the present invention, the medicament for treating androgenetic alopecia is a medicament for promoting the proliferation of human dermal papilla cells.

[0010] In some embodiments of the present invention, the drug for treating androgenic alopecia is a drug that inhibits the expression of androgen receptors.

[0011] In some embodiments of the present invention, the content of teicoplanin in the drug for treating androgenic alopecia is the content that reaches the therapeutically effective amount.

[0012] In some embodiments of the present invention, the content of teicoplanin in the drug for treating androgenic alopecia can be 0.1%-100%, such as 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, 99, 99.5, 100%.

[0013] In some embodiments of the present invention, the dosage of teicoplanin is 1-30 mg / Kg.

[0014] In some embodiments of the present invention, the dosage of teicoplanin is 5-20 mg / Kg.

[0015] In some embodiments of the present invention, the objects of drug treatment are mammals, including humans, mice, etc. Those skilled in the art can, according to the equal-dose conversion relationship between humans and experimental animals, infer the unit body weight dose of humans using the dose of animals. According to the unit body weight dose conversion, the equivalent dose of mice is about 9 times that of humans.

[0016] In some embodiments of the present invention, the drug for treating androgenic alopecia further includes a pharmaceutically acceptable carrier.

[0017] In some embodiments of the present invention, the pharmaceutically acceptable excipients include at least one of diluents, excipients, fillers, binders, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, sweeteners, and flavoring agents.

[0018] In some embodiments of the present invention, the excipient includes water.

[0019] In some embodiments of the present invention, the filler includes at least one of starch and sucrose.

[0020] In some embodiments of the present invention, the binder includes at least one of cellulose derivatives, alginates, gelatin, and polyvinylpyrrolidone.

[0021] In some embodiments of the present invention, the wetting agent includes glycerol.

[0022] In some embodiments of the present invention, the disintegrant includes at least one of agar, calcium carbonate, and sodium bicarbonate.

[0023] In some embodiments of the present invention, the absorption promoter includes quaternary ammonium compounds.

[0024] In some embodiments of the present invention, the surfactant includes cetyl alcohol.

[0025] In some embodiments of the present invention, the adsorption carrier includes at least one of kaolin and saponite.

[0026] In some embodiments of the present invention, the lubricant includes at least one of talc, calcium stearate, magnesium stearate and polyethylene glycol.

[0027] In some embodiments of the present invention, the administration methods of the drug for treating androgenetic alopecia include but are not limited to oral administration, enteral administration, subcutaneous injection, intramuscular injection, intravenous injection, nasal administration, transdermal administration, subconjunctival administration, intravitreal administration, orbital administration, retrobulbar administration, retinal administration, choroidal administration, intrathecal injection, and so on.

[0028] In some embodiments of the present invention, the dosage forms of the drug for treating androgenetic alopecia include but are not limited to tablets, capsules, pills, injections, inhalants, lozenges, suppositories, emulsions, microemulsions, submicroemulsions, nanoparticles, gels, powders, suspensions, creams, jellies, sprays, and so on. The various dosage forms of the drug can be prepared according to the conventional production methods in the pharmaceutical field.

[0029] In some embodiments of the present invention, the teicoplanin is the sole active ingredient of the drug for treating androgenetic alopecia, or is used as an active ingredient together with other drugs for treating androgenetic alopecia.

[0030] According to the second aspect of the present invention, a drug for treating androgenetic alopecia is provided, and the drug contains teicoplanin.

[0031] In some embodiments of the present invention, the drug further contains one or more drugs for treating androgenetic alopecia.

[0032] According to some embodiments of the present invention, it has at least the following beneficial effects: The teicoplanin of the present invention can effectively promote hair growth in the androgenetic alopecia area, inhibit androgen receptor expression, and promote the proliferation of dermal papilla cells. Compared with the existing drugs for treating androgenetic alopecia, it has fewer side effects and faster effects. Moreover, the teicoplanin selected in the present invention is a clinically approved drug, with few side effects, safe administration methods, wide drug sources, and simple and economical acquisition methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The present invention will be further described below in conjunction with the drawings and embodiments, where:

[0034] Figure 1 This is the result diagram of the effect of teicoplanin on AR in DPCs in Example 1 of the present invention;

[0035] Figure 2 This is the result diagram of the cytotoxicity experiment of the effect of teicoplanin on the growth of DPCs in Example 1 of the present invention;

[0036] Figure 3 This is the result diagram of the therapeutic effect of teicoplanin on AGA in C57BL-6 male mice in Example 1 of the present invention;

[0037] Figure 4 This is the result diagram of the therapeutic effect of teicoplanin on AGA in C57BL-6 male mice in Example 1 of the present invention, wherein, "*" represents P < 0.05, "***" represents P < 0.001, and ns represents no significant difference between groups;

[0038] Figure 5 This is the result diagram of the therapeutic effect of teicoplanin on AGA in C57BL-6 female mice in Example 1 of the present invention;

[0039] Figure 6 This is the result diagram of the therapeutic effect of teicoplanin on AGA in C57BL-6 female mice in Example 1 of the present invention, wherein, "**" represents P < 0.01, "***" represents P < 0.001.

[0040] Figure 7 This is the hematoxylin-eosin staining diagram of the liver after the treatment of AGA with teicoplanin in C57BL-6 male mice in Example 1 of the present invention, wherein the scale bar is 200 μm;

[0041] Figure 8 This is the hematoxylin-eosin staining diagram of the liver after the treatment of AGA with teicoplanin in C57BL-6 female mice in Example 1 of the present invention, wherein the scale bar is 200 μm. Detailed implementation manners

[0042] The following will clearly and completely describe the concept and technical effects generated by the present invention in combination with the embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative efforts shall fall within the protection scope of the present invention.

[0043] Test samples:

[0044] Teicoplanin was purchased from Shanghai Lanmu Chemical Co., Ltd.

[0045] Example 1

[0046] This example provides the application of teicoplanin in the preparation of drugs for the treatment of androgenetic alopecia. The specific verification process is as follows:

[0047] 1. Effect of teicoplanin on androgen receptor (AR) in human dermal papilla cells (DPCs)

[0048] Experimental method: After digesting human dermal papilla cells DPCs with 1 mL of trypsin, inoculate them into a 96-well plate, with 1.5×10 5 cells inoculated in each well. After overnight culture at 37°C for cell attachment, add teicoplanin groups with final concentrations of 0 μM, 10 μM, 20 μM, and 40 μM to the corresponding culture dishes. After culturing at 37°C for 24 h, lyse the cells in each well with 60 μL of RIPA lysis buffer to extract total protein. Take 25 μg of total protein for Western Blot experiment to analyze the expression of androgen receptor, with GAPDH as the reference gene.

[0049] The results are as Figure 1 shown. It can be seen from the figure that teicoplanin has a degradation effect on AR in DPCs.

[0050] 2. Effect of teicoplanin on the growth of DPCs for 24 hours

[0051] Experimental method:

[0052] (1) Prepare a 10 mM teicoplanin stock solution: Weigh teicoplanin powder with an electronic balance and dissolve it in dimethyl sulfoxide (DMSO) to prepare a stock solution with a concentration of 10 mM, and then dilute it with DMSO to different concentrations.

[0053] (2) After digesting DPCs with trypsin, inoculate them into a 96-well plate, with 5.5×10 3 cells inoculated in each well. After overnight culture at 37°C for cell attachment, add teicoplanin with final concentrations of 0 μM, 10 μM, 20 μM, 40 μM, 80 μM, and 160 μM to the corresponding culture dishes respectively. After culturing at 37°C for 24 hours, add 10 μL of MTT, incubate at 37°C for 4 hours. After 4 hours, aspirate the culture medium, add DMSO, react at room temperature on a shaker for 30 min, measure the absorbance at 570 nm, and then use GraphPad Prism8 to plot the fitted curve of drug concentration corresponding to cell viability.

[0054] The results are as Figure 2 shown. It can be seen from the figure that teicoplanin has low toxicity to DPCs and has a certain effect on promoting the proliferation of dermal papilla cells.

[0055] 3. Animal experiment

[0056] To verify the effect of teicoplanin in the treatment of AGA in vivo, C57BL-6 mice were selected to establish an AGA model for in vivo pharmacodynamic verification. The specific experimental method is as follows:

[0057] Experimental animals: 18 male C57BL-6 mice and 18 female C57BL-6 mice at 4-5 weeks of age were taken and raised stably in an SPF environment for one week.

[0058] Grouping: The C57BL-6 mice were randomly divided into a blank group (no drug administration) of 6 mice (no subcutaneous injection of DHT), among which, there were 3 males and 3 females; a modeling group of 30 mice. In the modeling group, DHT (5 mg / Kg) was subcutaneously injected into the back every day / time for 10 days to obtain an AGA mouse model.

[0059] Ten days after the establishment of the AGA mouse model, all mice were anesthetized by intraperitoneal injection of sodium pentobarbital at 10 mg / mL (0.4 mL / 100 g). The back skin of the mice was shaved short with an electric clipper, and depilatory cream was applied to the back of the mice for depilation treatment. The shaved mice were grouped as follows: The blank group was not treated; in the model group, there were 5 males and 5 females, and only DHT at 10 mg / Kg was subcutaneously injected every day; in the low-dose drug group, there were 5 males and 5 females, DHT at 10 mg / Kg was given every day, and teicoplanin at 10 mg / Kg was given on the first day, and teicoplanin at 5 mg / Kg was given every day thereafter for treatment; in the high-dose drug group, there were 5 males and 5 females, DHT at 10 mg / Kg was continuously given every day, and teicoplanin at 20 mg / Kg was given on the first day, and teicoplanin at 10 mg / kg was given every day thereafter for treatment.

[0060] Taking the day of depilation as the 0th day of the experiment, the hair growth of mice in each group was photographed and recorded on the 7th, 14th, and 17th days of the experiment, and the relative long hair area of mice in different groups was calculated on the 17th day. After 17 days, the experimental mice were sacrificed by cervical dislocation, the eyeballs of the mice were removed to collect blood, the blood was centrifuged at 3500 rpm at 4 °C for 20 minutes, and the serum was taken. The back skin of the mice was shaved short with an electric clipper, and depilatory cream was applied to the back of the mice for depilation treatment. The mice were dissected to obtain back skin tissue and liver, and the liver was photographed and weighed for recording.

[0061] The results are as Figures 3 - 8 shown. It can be seen from the figure that teicoplanin has a certain therapeutic effect on AGA, the high-dose teicoplanin has better pharmacodynamic effect than the low-dose, and the side effects are small.

[0062] The embodiments of the present invention have been described in detail above in conjunction with the accompanying drawings. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those of ordinary skill in the art, various changes can be made without departing from the purpose of the present invention. In addition, the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

Claims

1. The use of teicoplanin in the preparation of a drug for treating androgenic alopecia, characterized in that: The teicoplanin is the only active ingredient of the drug for treating androgenic alopecia.

2. The use according to claim 1, characterized in that: The androgenic alopecia is androgenic alopecia caused by testosterone.

3. The use according to claim 1, characterized in that: The drug for treating androgenic alopecia is a drug for promoting hair growth in androgenic alopecia areas.

4. The use according to claim 1, characterized in that: The drug for treating androgenic alopecia is a drug for promoting the proliferation of human hair papilla cells.

5. The use according to claim 1, characterized in that: The drug for treating androgenic alopecia is a drug that inhibits the expression of androgen receptors.

6. The use according to claim 1, characterized in that: The content of teicoplanin in the drug for treating androgenic alopecia is a content that reaches a therapeutically effective amount.

7. The use according to claim 1, characterized in that: The drug for treating androgenic alopecia further comprises a pharmaceutically acceptable carrier.

8. The use according to claim 1, characterized in that: The dosage form of the drug for treating androgenic alopecia is an injection; And / or, the drug for treating androgenic alopecia is administered by subcutaneous injection.

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