Composition for inhibiting activity of 5 alpha-reductase and application thereof

Abstract

The invention relates to the technical field of functional preparations, in particular to a composition for inhibiting activity of 5 alpha-reductase and application of the composition. The composition disclosed by the invention is prepared from the following components in parts by weight: 1 to 40 parts of lycopene, 80 to 400 parts of phytosterol and / or phytosterol ester and 0.7 to 3.3 parts of melia azedarach leaf evodia rutaecarpa cornus officinalis B. In the composition, all the components are mutually matched and supplement each other, the composition has a remarkable effect of inhibiting the activity of 5alpha-reductase, and androgen dependent diseases such as androgenetic alopecia, benign prostatic hyperplasia and the like can be effectively improved. The raw materials of the composition are all natural active components, so that the composition has good effects of improving benign prostatic hyperplasia and inhibiting androgenetic alopecia, is safe and effective, and has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the field of functional formulation technology, and in particular to a composition that inhibits 5α-reductase activity and its application. Background Technology

[0002] 5α-reductase is a microsomal enzyme with a wide range of biological functions. It relies on reduced coenzyme II (NADPH) as a hydrogen donor to catalyze the reduction of a series of 3-oxo-Δ4steroid compounds, including testosterone, at the Δ4,5 double bond, resulting in the addition of hydrogen at the C-5 position to the α position, forming the corresponding 5α-hydroxylated product. 5α-reductase is mainly found in the prostate, seminal vesicle, epididymis, and hair follicles. Overexpression of 5α-reductase leads to high levels of dihydrotestosterone (DHT). DHT, a more potent androgen than testosterone, has five times the binding capacity to the androgen receptor (AR) and plays an important role in multiple organs and tissues, including the reproductive system, skin, and hair. However, high levels of DHT can easily cause androgen-dependent diseases such as acne, hirsutism, androgenetic alopecia, benign prostatic hyperplasia (BPH), and prostate cancer. Therefore, inhibiting 5α-reductase is one of the important means of treating androgen-dependent diseases such as BPH, androgenetic alopecia, and acne.

[0003] Currently, drugs for treating androgen-dependent diseases based on inhibiting 5α-reductase mainly include finasteride, dutasteride, and acepril. However, these synthetic 5α-reductase inhibitors are prone to side effects. Therefore, it is of great significance to develop a product that uses natural plant ingredients as raw materials and has the ability to inhibit 5α-reductase activity. Summary of the Invention

[0004] This invention provides a composition for inhibiting 5α-reductase activity and its application.

[0005] Specifically, the present invention provides the following technical solutions.

[0006] In a first aspect, the present invention provides a composition comprising the following components in parts by weight: 1-40 parts of lycopene, 80-400 parts of phytosterols and / or phytosterol esters, and 0.7-3.3 parts of neem leaf ethionin B.

[0007] Lycopene, as a potent antioxidant, can scavenge free radicals in the body and reduce oxidative stress damage. Phytosterols and phytosterol esters have effects such as lowering cholesterol, improving symptoms of benign prostatic hyperplasia, and anti-inflammation. Neem leaf erythritol B has antioxidant and anti-inflammatory effects, and can significantly inhibit the production of superoxide anions by human neutrophils under the stimulation of formyl peptide (fMLP / CB), reducing oxidative stress damage to tissues. Currently, there are no reports of using neem leaf erythritol B to inhibit 5α-reductase activity or treat androgen-dependent diseases. However, this invention unexpectedly discovered that although neem leaf erythritol B itself does not have a significant effect on inhibiting 5α-reductase activity or improving androgen-dependent diseases, when lycopene and phytosterols (or phytosterol esters) are combined with neem leaf erythritol B in the above ratio, the three can work synergistically to significantly improve the efficacy of the compound composition in inhibiting 5α-reductase activity and improving androgen-dependent diseases (such as androgenetic alopecia and benign prostatic hyperplasia), which is significantly improved compared to the efficacy of each single component and the composition of lycopene and phytosterols (or phytosterol esters).

[0008] In this invention, the phytosterols include one or more selected from β-sitosterol, stigmasterol, and campesterol.

[0009] In this invention, the phytosterol esters include one or more selected from β-sitosterol esters, stigmasterol esters, and campesterol esters.

[0010] Preferably, the phytosterol is β-sitosterol.

[0011] Preferably, the composition comprises the following components in parts by weight: 1-40 parts lycopene, 80-400 parts β-sitosterol, and 0.7-3.3 parts neem leaf erythritol B.

[0012] This invention demonstrates through experiments that lycopene and β-sitosterol can work synergistically with neem leaf erythritol B within the above-mentioned ratio range. The combination of the three components has excellent effects in inhibiting 5α-reductase activity and improving androgen-dependent diseases, and its efficacy is significantly improved compared with that of each single component and the combination of lycopene and β-sitosterol.

[0013] In some embodiments of the present invention, the composition comprises the following components in parts by weight: 10-20 parts of lycopene, 200-300 parts of β-sitosterol, and 1-3 parts of neem leaf erythritol B.

[0014] In some embodiments of the present invention, the composition comprises the following components in parts by weight: 13-17 parts of lycopene, 220-250 parts of β-sitosterol, and 1-2 parts of neem leaf erythritol B.

[0015] The above-described composition has any one or more of the following functions: (1) Inhibits 5α-reductase activity; (2) Prevention, treatment and / or relief of androgen-dependent diseases; (3) Reduce androgen levels in patients with androgen-dependent diseases; (4) Promotes hair growth in patients with androgenetic alopecia; (5) Improve androgenetic alopecia.

[0016] Preferably, the inhibition of 5α-reductase activity is inhibited in patients with androgen-dependent diseases.

[0017] The androgen-dependent diseases mentioned include, but are not limited to, androgenetic alopecia and benign prostatic hyperplasia (BPH). The prevention, treatment, and / or relief of BPH include reducing prostate weight and lowering the prostate index.

[0018] The androgen content is preferably dihydrotestosterone content.

[0019] Secondly, the present invention provides a method for preparing the above-described composition, comprising the step of mixing lycopene, phytosterols and / or phytosterol esters, and neem leaf erythrin B.

[0020] As an example, the preparation method of the composition includes the following steps: S1: weigh each raw material according to the weight parts; S2: put each raw material into the equipment, stir and mix thoroughly for 20-25 minutes, and mix evenly.

[0021] Thirdly, the present invention provides the use of the above-described compositions in the preparation of food or pharmaceutical compositions.

[0022] Based on its efficacy, the composition in the first aspect described above can be used to prepare food, especially health food. In addition to the composition, the food may also contain excipients permitted in the food industry. Based on its efficacy, the composition in the first aspect described above can be used to prepare pharmaceutical compositions, the active ingredient of which may include or consist solely of the composition in the first aspect described above. In addition to the active ingredient, the pharmaceutical composition may also include excipients permitted in the pharmaceutical industry. These excipients include, but are not limited to, fillers, binders, disintegrants, lubricants, flavoring agents, colorants, preservatives, pH adjusters, solubilizers, stabilizers, emulsifiers, antioxidants, flow aids, coating materials, etc. The specific types of excipients can be selected according to the dosage form of the food or pharmaceutical composition.

[0023] The dosage forms of the food or pharmaceutical composition include, but are not limited to, tablets, capsules, granules, powders, solutions, powders, emulsions, or suspensions.

[0024] Fourthly, the present invention provides the use of the above-described composition in the preparation of products having any one or more of the following functions: (1) Inhibits 5α-reductase activity; (2) Prevention, treatment and / or relief of androgen-dependent diseases; (3) Reduce androgen levels in patients with androgen-dependent diseases; (4) Promotes hair growth in patients with androgenetic alopecia; (5) Improve androgenetic alopecia.

[0025] Preferably, the inhibition of 5α-reductase activity is inhibited in patients with androgen-dependent diseases.

[0026] The androgen-dependent diseases mentioned include, but are not limited to, androgenetic alopecia and benign prostatic hyperplasia (BPH). The prevention, treatment, and / or relief of BPH include reducing prostate weight and lowering the prostate index.

[0027] The androgen content is preferably dihydrotestosterone content.

[0028] Preferably, the product is a food or pharmaceutical composition.

[0029] Fifthly, the present invention provides any one or more of the following applications of the compositions described above: (1) Inhibits 5α-reductase activity; (2) Prevention, treatment and / or relief of androgen-dependent diseases; (3) Reduce androgen levels in patients with androgen-dependent diseases; (4) Promotes hair growth in patients with androgenetic alopecia; (5) Improve androgenetic alopecia.

[0030] In a sixth aspect, the present invention provides a product comprising the composition described in the first aspect.

[0031] Preferably, the product is a food or pharmaceutical composition.

[0032] Preferably, the food is a health food. In addition to the composition, the food may also contain excipients permitted in the food industry. Preferably, the active ingredient of the pharmaceutical composition may include the composition described in the first aspect above, or may consist solely of the composition described in the first aspect above. In addition to the active ingredient, the pharmaceutical composition may also include excipients permitted in the pharmaceutical industry. These excipients include, but are not limited to, fillers, binders, disintegrants, lubricants, flavoring agents, colorants, preservatives, pH adjusters, solubilizers, stabilizers, emulsifiers, antioxidants, flow aids, coating materials, etc. The specific types of excipients may be selected according to the dosage form of the food or pharmaceutical composition.

[0033] The dosage forms of the food or pharmaceutical composition include, but are not limited to, tablets, capsules (e.g., soft capsules), granules, powders, solutions, powders, emulsions, or suspensions.

[0034] Preferably, the food or pharmaceutical composition is a food or pharmaceutical composition for oral administration, a pharmaceutical composition for injection, or a pharmaceutical composition for topical application.

[0035] The beneficial effects of this invention include at least the following: the components in the composition provided by this invention work synergistically to significantly inhibit 5α-reductase activity, effectively improving androgen-dependent diseases such as androgenetic alopecia and benign prostatic hyperplasia. Furthermore, the raw materials of this composition are all natural active ingredients, exhibiting good effects in improving prostatic hyperplasia and inhibiting androgenetic alopecia, and are safe, effective, and have broad application prospects. Detailed Implementation

[0036] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0037] Unless otherwise specified, the experimental methods used in the following examples are conventional methods; the materials and reagents used, unless otherwise specified, can be obtained from conventional commercial sources or prepared according to conventional methods in the art. Among them, lycopene, β-sitosterol, and neem leaf erythritol B can all be purchased from commercial sources.

[0038] The compositions in the following examples can be prepared using conventional methods. For example, the preparation method includes the following steps: weighing each raw material according to the weight ratio; putting each raw material into the equipment and mixing thoroughly for 25 minutes until uniform; and quantitatively dispensing the uniformly mixed material using an automatic filling machine to obtain the final product.

[0039] Example 1 This embodiment provides a composition comprising the following components in parts by weight: 15 parts lycopene, 240 parts β-sitosterol, and 1.5 parts neem leaf erythritol B.

[0040] Example 2 This embodiment provides a composition comprising the following components in parts by weight: 1 part lycopene, 80 parts β-sitosterol, and 0.7 parts neem leaf erythritol B.

[0041] Example 3 This embodiment provides a composition, which is composed of the following components in parts by weight: 40 parts of lycopene, 400 parts of β-sitosterol, and 3.3 parts of evodiamine B.

[0042] Comparative Example 1 This comparative example provides a composition, which is composed of the following components in parts by weight: 15 parts of lycopene and 240 parts of β-sitosterol.

[0043] Comparative Example 2 This comparative example provides a product that consists only of lycopene.

[0044] Comparative Example 3 This comparative example provides a product that consists only of β-sitosterol.

[0045] Comparative Example 4 This comparative example provides a product that consists only of evodiamine B.

[0046] Comparative Example 5 This comparative example provides a composition, which is composed of the following components in parts by weight: 0.8 part of lycopene, 70 parts of β-sitosterol, and 0.5 part of evodiamine B.

[0047] Comparative Example 6 This comparative example provides a composition, which is composed of the following components in parts by weight: 41 parts of lycopene, 410 parts of β-sitosterol, and 3.5 parts of evodiamine B.

[0048] Comparative Example 7 This comparative example provides a composition, which is composed of the following components in parts by weight: 15 parts of lycopene, 240 parts of β-sitosterol, and 1.5 parts of curcumin.

[0049] Experimental Example 1 Animal Experiment for Improving Benign Prostatic Hyperplasia Animal experiments were conducted on the compositions or products of the above-mentioned embodiments and comparative examples to test their efficacy in improving benign prostatic hyperplasia. The specific methods and results are described as follows.

[0050] 1. Test Consumables (1) Materials Test samples: Compositions or products of Embodiments 1-3 and Comparative Examples 1-7, stored in the dark and sealed at 4°C; Experimental animals: SPF-grade male SD rats (180-220 g); Source: Beijing Spearf Bio-Technology Co., Ltd. [Production License Number: SCXK (Beijing) 2024-0001]; Positive drug: Qianliekang; Feed and bedding.

[0051] (2) Reagents Testosterone propionate, dihydrotestosterone (DTH), 5-α reductase enzyme-linked immunosorbent assay kit, etc., were all purchased from Shanghai Enzyme-Linked Biotechnology Co., Ltd.

[0052] (3) Instruments YH-M20001 electronic balance, AUW220 electronic balance, centrifuge, ELISA reader, gavage needle, dissecting instruments, etc.

[0053] 2. Experimental Methods (1) Animal grouping and administration Experimental animals were observed for 5 days under a maintenance diet within a barrier system. Rats were randomly divided into 13 groups based on body weight: a blank control group, a model control group, a positive control group (using a prostate extract), groups 1-3 of Examples, and groups 1-7 of Comparative Examples, with 10 rats in each group. Except for the blank control group, which was injected with corn oil (injection volume 1 mL / kg BW), all other groups received subcutaneous injections of testosterone propionate (5 mg / kg BW) in the back once daily for 30 consecutive days. From the first day of model establishment, the Example and Comparative Example groups were administered solutions of the compositions of the Examples or the compositions or products of the Comparative Examples or ... On day 30 of modeling, 24 hours after the last administration of testosterone propionate to establish the model, each experimental group was fasted for 16 hours but allowed free water. They were weighed, anesthetized with chloral hydrate, sacrificed, and blood was collected from the abdominal aorta. The prostate was then removed, weighed, and the prostate index was calculated. The prostate index (%) = prostate weight / body weight × 100.

[0054] (2) Indicator detection Enzyme activity index: 5-α reductase activity; Hormone level: Dihydrotestosterone (DHT) content; Apparent indicators: prostate weight, prostate index.

[0055] 3. Results Statistics and Analysis All data are expressed as mean ± standard deviation and statistical analysis was performed using SPSS 21.0 software. If the variances of the measurement data are homogeneous, or if the variances are homogeneous after transformation, one-way ANOVA was used. If the variances are still heterogeneous after transformation, the rank-sum test was used for statistical analysis.

[0056] 4. Test Results (1) Enzyme activity and hormone indicators After collecting blood from the abdominal aorta of rats, centrifuge at 3500 r / min for 15 min, take the supernatant, and detect the 5α-reductase activity and dihydrotestosterone content according to the kit instructions.

[0057] The results of 5α-reductase activity and dihydrotestosterone content are shown in Table 1.

[0058] Table 1

[0059] Note: Different letters represent significant differences between groups (P < 0.05).

[0060] From the data in Table 1, it can be seen that compared with the blank group, the 5α-reductase activity of rats in the model group was significantly enhanced, and the dihydrotestosterone content was significantly increased, thus inducing prostate hyperplasia in experimental animals. The compositions of Administration Examples 1-3 can significantly reduce the 5α-reductase activity and dihydrotestosterone content of rats with prostate hyperplasia. Especially compared with the positive drug (Prostate Health) and each comparative example, the compositions of Examples 1-3 have significantly better effects in improving prostate hyperplasia.

[0061] (2) Apparent indicators The results of prostate weight and index are shown in Table 2. <000017​​​​​​​​​​​​​​​​​​​​​​​​ Feed and bedding.

[0067] (2) Reagents Testosterone propionate, ethanol, propylene glycol.

[0068] (3) Instruments YH-M20001 Electronic Balance.

[0069] 2. Experimental Methods (1) Animal grouping and administration The experimental animals were maintained on a maintenance diet under the barrier system for 5 days. Mice were then randomly divided into two groups based on body weight: a control group of 10 mice and a model group of 132 mice. The control group was injected with corn oil at a volume of 1 mL / kg body weight (BW), while the model groups received subcutaneous injections of testosterone propionate (5 mg / kg BW) in the back once daily for 4 weeks. Hair was then removed from the backs of 110 successfully modeled androgenetic alopecia mice using depilatory cream, covering a 2×3 cm area. These mice were subsequently randomly divided into a model group, Examples 1-3, and Comparative Examples 1-7, with 10 animals in each group. Each group was treated with 200 μL of the corresponding solution daily: the blank group and the model group were treated with the control solvent (corn oil), and the groups of Examples 1-3 and the groups of Comparative Examples 1-7 were treated with the solution of the composition of Examples 1-3 and the solution of the composition or product of Comparative Examples 1-7, respectively. The solvent of the solution was corn oil. The administration concentration of the solution of the composition of Examples 1-3 and the solution of the composition or product of Comparative Examples 1-7 was 10 mg / mL. After 28 consecutive days of treatment, the mice were scored according to the hair growth.

[0070] (2) Indicator detection: Hair growth in mice.

[0071] The mice were scored based on their hair growth, with the following criteria: 0 points for no hair growth, 1 point for light hair covering the bald area, 2 points for new hair length and density being about half that of the non-bald area, and 3 points for new hair length being no different from the non-bald area. Mice with irregular hair growth were scored based on area ratio.

[0072] 3. Results Statistics and Analysis All data are expressed as mean ± standard deviation and statistical analysis was performed using SPSS 21.0 software. If the variances of the measurement data are homogeneous, or if the variances are homogeneous after transformation, one-way ANOVA was used. If the variances are still heterogeneous after transformation, the rank-sum test was used for statistical analysis.

[0073] 4. Test Results The hair growth scores of mice are shown in Table 3.

[0074] Table 3 Scoring of mouse hair growth

[0075] Note: Different letters indicate significant differences between groups (P < 0.05).

[0076] As shown in Table 3, compared with the control group, the model group mice showed significant hair loss after injection of testosterone propionate, indicating successful modeling. Compared with the comparative proportions, the compositions of Examples 1-3 significantly increased hair growth in androgenetic alopecia mice, indicating that the compositions of the examples have a good effect in improving androgenetic alopecia.

[0077] In summary, the composition of the present invention has a good inhibitory effect on 5α-reductase activity and can effectively alleviate and treat androgen-dependent diseases such as benign prostatic hyperplasia and androgenic alopecia.

[0078] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A composition, characterized in that, The composition comprises the following components in parts by weight: 1-40 parts of lycopene, 80-400 parts of phytosterols and / or phytosterol esters, and 0.7-3.3 parts of neem leaf ethionin B.

2. The composition according to claim 1, characterized in that, The phytosterols include one or more selected from β-sitosterol, stigmasterol and campesterol; The phytosterol esters include one or more selected from β-sitosterol esters, stigmasterol esters, and campesterol esters.

3. The composition according to claim 1 or 2, characterized in that, The composition comprises the following components in parts by weight: 1-40 parts lycopene, 80-400 parts β-sitosterol, and 0.7-3.3 parts neem leaf erythritol B.

4. The composition according to any one of claims 1 to 3, characterized in that, The composition has any one or more of the following functions: (1) Inhibits 5α-reductase activity; (2) Prevention, treatment and / or relief of androgen-dependent diseases; (3) Reduce androgen levels in patients with androgen-dependent diseases; (4) Promotes hair growth in patients with androgenetic alopecia; (5) Improve androgenetic alopecia.

5. The composition according to claim 4, characterized in that, The androgen-dependent diseases include androgenetic alopecia or benign prostatic hyperplasia.

6. Use of the composition according to any one of claims 1 to 5 in the preparation of food or pharmaceutical compositions.

7. The use of the composition according to any one of claims 1 to 5 in the preparation of a product having any one or more of the following functions: (1) Inhibits 5α-reductase activity; (2) Prevention, treatment and / or relief of androgen-dependent diseases; (3) Reduce androgen levels in patients with androgen-dependent diseases; (4) Promotes hair growth in patients with androgenetic alopecia; (5) Improve androgenetic alopecia.

8. The application according to claim 7, characterized in that, The androgen-dependent diseases include androgenetic alopecia or benign prostatic hyperplasia.

9. A product characterized in that, The product includes the composition according to any one of claims 1 to 5.

10. The product according to claim 9, characterized in that, The product is a food or pharmaceutical composition.

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