阅读说明：本技术 红花黄色素在制备II型5α-还原酶抑制剂中的应用 (Application of safflower yellow in preparation of II-type 5 alpha-reductase inhibitor ) 是由 沈志滨 胡锡昌 张衍湖 ***榕 于 2020-05-08 设计创作，主要内容包括：本发明公开了红花黄色素在制备II型5α-还原酶抑制剂中的应用,同时,红花黄色素还能够应用于制备治疗雄激素依赖型疾病的药物,所述雄激素依赖型疾病包括前列腺增生、多毛症、雄激素源性脱发和痤疮。红花黄色素具有较强的II型5α-还原酶抑制活性,其体外最低有效抑制浓度可达69μM；在多种中药活性成分中,红花黄色素具有较好的与II型5α-还原酶蛋白对接的效果,且其效果高于目前常用的II型5α-还原酶抑制剂——非那雄胺,说明其与II型5α-还原酶的结合能力强,具有较好的II型5α-还原酶抑制活性。(The invention discloses application of safflower yellow in preparing a II-type 5 alpha-reductase inhibitor, and meanwhile, the safflower yellow can also be applied to preparing a medicament for treating androgen-dependent diseases, wherein the androgen-dependent diseases comprise prostatic hyperplasia, hirsutism, androgen-induced alopecia and acne. The safflower yellow has stronger II-type 5 alpha-reductase inhibition activity, and the minimum effective inhibition concentration in vitro can reach 69 mu M; among a plurality of traditional Chinese medicine active ingredients, the safflower yellow has better docking effect with II type 5 alpha-reductase protein, and the effect is higher than that of the currently common II type 5 alpha-reductase inhibitor, namely finasteride, which shows that the safflower yellow has strong binding capacity with II type 5 alpha-reductase and better II type 5 alpha-reductase inhibition activity.)

1. Use of safflower yellow in preparing type II 5 alpha-reductase inhibitor is provided.

2. Use of safflower yellow in the preparation of a product for the treatment of androgen dependent diseases.

3. The use of claim 2, wherein the androgen-dependent disease comprises at least one of prostatic hyperplasia, hirsutism, androgenic alopecia, and acne.

4. Use according to claim 2 or 3, wherein the product is in the form of capsules, tablets, oral preparations, microcapsules, injections, suppositories, sprays or ointments.

5. Application of safflower yellow in preparing hair loss preventing and hair strengthening product is provided.

6. A type II 5 alpha-reductase inhibitor characterized in that the active ingredient thereof comprises safflor yellow.

7. A medicine for treating androgen-dependent diseases is characterized in that the active component of the medicine contains safflower yellow.

8. A pharmaceutical composition for treating androgen-dependent diseases, characterized in that its active ingredient comprises safflower yellow.

9. An anti-hair loss and hair-fixing product is characterized in that the active component of the product contains safflower yellow.

10. The product according to claim 9, wherein the safflower yellow is contained in an amount of 0.01 to 0.5% by weight.

Technical Field

The invention relates to the technical field of medicines, in particular to application of safflower yellow in preparing a II-type 5 alpha-reductase inhibitor.

Background

Safflower (Carthamus tinctorius L.), alias: carthamus tinctorius flower and Carthamus spinosus flower belonging to Compositae and Carthamus. Carthami flos has effects of promoting blood circulation, dredging channels, removing blood stasis, and relieving pain, and can be used for treating amenorrhea, dysmenorrhea, lochiorrhea, thoracic obstruction, cardialgia, blood stasis, abdominal pain, pricking pain in chest and hypochondrium, traumatic injury, pyocutaneous disease, and swelling and pain.

Safflower is a Chinese herbal medicine with high safety and multiple active potentials. Safflower contains many active chemical components including flavonoids, lignans, alkaloids, linoleic acids, etc. The safflower yellow is a flavonoid compound in traditional Chinese medicine safflower, and has the effects of anticoagulation, antithrombotic, antioxidation, immunoregulation, tumor resistance and the like (Liu Shi Jun, Tang Shi Shu, Cuichui, and the like, research on chemical components of traditional Chinese medicine safflower is advanced [ J ]. Henan traditional Chinese medicine, 2017 (1)). The chemical structural formula of the carthamus tinctorius yellow colour is as follows:

5 alpha-reductase (5 alpha-reductase, 5 alpha R) is a microsomal, membrane protease that catalyzes the reduction of steroid hormones by means of a reducing coenzyme II, and includes both type I (5 alpha R1) and type II (5 alpha R2) isozymes. Among them, 5 α R1 is mainly distributed in androgen-independent organs in the human body, such as liver and brain; 5 α R2 is found in large amounts in androgen-dependent organs such as the hair follicle root sheath, prostate and epididymis (Inui S, Itami S. android actions on the human hairpin: perspectives [ J ]. Experimental Dermatology,2013,22(3): 168-. In human body, 5 alpha-reductase is a key enzyme for catalyzing testosterone (T) to be more active Dihydrotestosterone (DHT), and high-level DHT is easy to cause androgen-dependent diseases (Pansheng, Wangyongcheng, Chuilimin. the role of 5 alpha-reductase in related diseases [ J ] medical review, 2011,17(17): 2571-. The reduction of androgen levels by inhibition of 5 α -reductase has become an important approach to the treatment of androgen-dependent diseases such as benign prostatic hyperplasia, androgenetic alopecia and the like (Liuben, Mirabilis, Chenguli. research on 5 α -reductase as a target for natural drug screening [ J ] drug biology, 2006(06): 468-.

At present, the 5 alpha-reductase inhibitors commonly used in clinic are mainly steroid drugs such as finasteride and dutasteride, but all of them have strong adverse reactions such as erectile dysfunction, sexual dysfunction, decreased sexual libido, feminization of male breasts, etc. (Banday AH, shamemem S a, Jeelani S. step pyrazolines and pyrazoles potential5 alpha-reduction enzyme inhibitors: Synthesis and biological evaluation [ J ]. steps, 2014,92:13-19), so that it is especially necessary to search for novel inhibitors with high activity and less side effects from Chinese herbal medicines. The inhibitory effect of safflower yellow on type II 5 alpha-reductase has not been reported at present.

Disclosure of Invention

The present invention is directed to solving at least one of the problems of the prior art. Therefore, the research shows that the safflower yellow has good inhibiting effect on the II type 5 alpha-reductase.

In a first aspect of the invention, there is provided the use of safflower yellow for the preparation of a type II 5 α -reductase inhibitor.

According to some embodiments of the invention, safflor yellow is capable of inhibiting the biological activity of type II 5 α -reductase in vitro.

In a second aspect of the invention, there is provided the use of safflower yellow in the manufacture of a product for the treatment of androgen dependent diseases.

According to some embodiments of the invention, the androgen-dependent disease comprises at least one of prostatic hyperplasia, hirsutism, androgenic alopecia and acne.

According to some embodiments of the invention, the product is in the form of a capsule, tablet, oral preparation, microcapsule, injection, suppository, spray or ointment.

In a third aspect of the present invention, there is provided the use of safflower yellow for the manufacture of a hair loss preventing and hair setting product.

Type II 5 alpha-reductase inhibitors are commonly used in the treatment of androgen-dependent diseases such as prostatic hyperplasia, hirsutism, androgenic alopecia and acne. Among them, androgenetic alopecia (also called seborrheic alopecia) is alopecia caused by androgen secretion, because a large amount of 5 alpha-reductase in hair follicles can convert male hormones to generate a large amount of metabolite dihydrotestosterone, and the hair follicles begin to atrophy and degenerate to begin to fall. At present, the treatment mode and the treatment effect of androgenetic alopecia are limited, and the requirements of people on alopecia treatment cannot be met; the invention discovers that the safflower yellow has better II-type 5 alpha-reductase inhibition, so the anti-hair loss and hair-fixing product containing the safflower yellow is prepared by taking the safflower yellow as an active ingredient for treating the androgenetic alopecia, can be widely applied to the prevention and treatment of the androgenetic alopecia and has better anti-hair loss and hair-fixing effects.

In a fourth aspect of the present invention, there is provided a type II 5 α -reductase inhibitor, the active ingredient of which comprises safflor yellow.

In a fifth aspect of the present invention, there is provided a medicament for treating androgen-dependent diseases, the active ingredient of which comprises safflower yellow.

According to some embodiments of the invention, the safflower yellow is proved to have stronger II-type 5 alpha-reductase inhibitory activity and application prospect in the treatment of related androgen-dependent diseases; according to the safety data in the embodiment of the invention, the safflor yellow is proved to have high safety and low toxicity, and meets the requirements of preparing related medicines.

In a sixth aspect of the present invention, there is provided a pharmaceutical composition for treating androgen-dependent diseases, the active ingredient of which comprises safflor yellow.

In a seventh aspect of the present invention, there is provided an anti-hair loss and hair-fixing product, wherein the active ingredient comprises safflor yellow.

According to some embodiments of the invention, the safflower yellow is present in an amount of 0.01 to 0.5% by weight.

In the present invention, the product includes a drug or a cosmetic.

In the present invention, the term "treating" includes alleviating, inhibiting or ameliorating the symptoms or conditions of a disease; inhibiting the generation of complications: ameliorating or preventing underlying metabolic syndrome; inhibiting the development of a disease or condition, such as controlling the development of a disease or condition; alleviating the disease or symptoms; regression of the disease or symptoms; alleviating a complication caused by the disease or symptom, or preventing or treating a symptom caused by the disease or symptom. As used herein, administration can result in an improvement in a disease, symptom, or condition, particularly an improvement in severity, delay in onset, slow progression, or decrease in duration of a condition. Whether fixed or temporary, sustained or intermittent, can be attributed to conditions associated with administration.

The invention has the beneficial effects that:

1. the safflower yellow has stronger II-type 5 alpha-reductase inhibition activity, and the minimum effective inhibition concentration in vitro can reach 69 mu M; among a plurality of traditional Chinese medicine active ingredients, the safflower yellow has better docking effect with II type 5 alpha-reductase protein, and the effect is higher than that of the currently common II type 5 alpha-reductase inhibitor, namely finasteride, which shows that the safflower yellow has strong binding capacity with II type 5 alpha-reductase and better II type 5 alpha-reductase inhibition activity;

2. the safflower yellow is an active ingredient derived from natural plant safflower, and has high safety, low toxicity and little side effect;

3. the prepared product containing the safflower yellow has good effects of preventing hair loss and fixing hair on the treatment of the alopecia caused by androgen.

Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.

Drawings

FIG. 1 is a pull chart of an optimum model in example 1 of the present invention;

FIG. 2 is a 3D model structure diagram in embodiment 1 of the present invention;

FIG. 3 is a diagram showing a binding pattern of safflower yellow to type II 5. alpha. -reductase in example 1 of the present invention;

FIG. 4 shows RMSD values of amino acid backbone atoms of type II 5. alpha. -reductase in example 2 of the present invention as a function of time;

FIG. 5 is a diagram showing RMSF value fluctuation of amino acid skeleton atoms of a ligand-protein complex in example 2 of the present invention;

FIG. 6 is a graph showing the results of a chicken chorioallantoic membrane (CAM) vasoreactivity assay with safflor yellow and related products of example 5 in accordance with the present invention;

FIG. 7 is a graph showing the patch test results of the safflor yellow pigment in example 5 of the present invention.

Detailed Description

In order to explain technical contents, achieved objects, and effects of the present invention in detail, the following description is made with reference to the accompanying drawings in combination with the embodiments.

Materials and instruments: LC-20A high performance liquid chromatograph (Shimadzu corporation, Japan); chromatography column (COSMOSIL 5C18-MS-II column (250mm x 2.6, 5 μm)); TGL-16 type high speed low temperature centrifuge (Hunan instruments laboratory development Co., Ltd., Hunan); model SB-1200 constant temperature water bath (shanghai alexander instruments ltd).

Safflower yellow (CAS: 36383-96-2, 98%, Chengdu Egya method Biotech Co., Ltd., lot number AF 8030707); reducing coenzyme II (NADPH, > 98%, Shanghai Michelin Biotechnology Ltd., batch No. C10526802); dithiothreitol (DTT, > 98%, Shanghai Michelin Biochemical technology Ltd., lot No. C10182317); phenylmethylsulfonyl fluoride (PMSF, > 98%, Shanghai Michelin Biochemical technology Co., Ltd., batch No. C10090911); the methanol is chromatographically pure; the rest reagents are analytically pure, and the water is deionized water.

SD rats, 9 weeks old, weight 260-: SCXK (yue) 2018-: SYXK (Yue) 2017-0125 ].

And (3) statistical data analysis: the data obtained in this example were analyzed using the software SPASS 23.0. Each group of data is expressed as 'x +/-s', single-factor analysis of variance is adopted for comparison among groups, if the homogeneity of variance is detected by an LSD method, the Dunnett T3 method is adopted for detection when the variance is not uniform, and P <0.05 indicates that the difference has statistical significance.