Rape pollen and maca chewable tablet for resisting benign prostatic hyperplasia and preparation method of rape pollen and maca chewable tablet

Abstract

The invention provides rape pollen and maca chewable tablets for resisting benign prostatic hyperplasia and a preparation method of the rape pollen and maca chewable tablets, and relates to the technical field of biological medicines. The rape pollen and maca chewable tablet takes a rape pollen extract and a maca extract as effective components, the rape pollen extract is obtained by performing high-voltage pulsed electric field treatment and ultrasonic extraction on rape pollen through a deep-eutectic solvent solution, and the maca extract is obtained by performing microbial anaerobic fermentation on maca powder. The rape pollen extract disclosed by the invention can inhibit 5alpha-reductase and reduce the generation of dihydrotestosterone; the maca extract can regulate an endocrine axis, improve immunity and microcirculation, relieve slight gastrointestinal irritation possibly brought by the rape pollen extract and improve the taking safety and compliance of the whole preparation; and the rape pollen extract and the maca extract have a synergistic effect, so that the prostatic hyperplasia can be remarkably inhibited. The chewable tablet can inhibit benign prostatic hyperplasia and can be used for preparing drugs for preventing and treating benign prostatic hyperplasia.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, specifically to a rapeseed pollen and maca chewable tablet for treating benign prostatic hyperplasia and its preparation method. Background Technology

[0002] Benign prostatic hyperplasia (BPH) is a common urinary system disease in middle-aged and elderly men, mainly characterized by non-malignant enlargement of prostate tissue, leading to symptoms such as urinary frequency, urgency, and difficulty urinating, severely impacting quality of life. With the increasing aging of the global population, the incidence of BPH continues to rise, becoming a significant public health issue. Currently, Western medicine treatment mainly relies on alpha-receptor blockers (such as tamsulosin) and 5α-reductase inhibitors (such as finasteride), but these drugs have side effects such as dizziness and sexual dysfunction, and long-term use may lead to drug resistance. Therefore, developing safe and effective alternative therapies or functional foods derived from natural plants has become a research hotspot in the medical and health industries.

[0003] Rapeseed pollen is a traditional natural medicine widely used to improve prostate health. Studies have shown that rapeseed pollen has anti-inflammatory, antioxidant, and endocrine-regulating effects, and can inhibit prostate cell proliferation and relieve urethral pressure. However, pollen itself has the problem of hard cell walls and low direct absorption rate by the human body.

[0004] Maca, a medicinal plant native to Peru, has gained attention in recent years for its functions of enhancing immunity, combating fatigue, and regulating hormone balance. Studies have shown that it can indirectly inhibit prostate hyperplasia by regulating testosterone metabolism and antioxidant pathways, and its synergistic effect with pollen may enhance its therapeutic effects.

[0005] Currently, there are some pollen or maca-related products on the market (such as capsules and tablets), but most of them are single-ingredient dietary supplements, lacking a compound formula design specifically for benign prostatic hyperplasia (BPH). Furthermore, traditional tablets have problems such as difficulty swallowing and poor taste, especially leading to lower compliance among elderly patients. Chewable tablets, as a novel dosage form, do not require water and have easily adjustable taste, making them more suitable for middle-aged and elderly people; however, research on combining pollen and maca to prepare chewable tablets has not yet been reported.

[0006] Therefore, developing a chewable tablet product that combines the synergistic anti-prostate hyperplasia effects of rapeseed pollen and maca, and enhances user experience through dosage form innovation, has significant application value. This product can not only compensate for the shortcomings of existing drugs but also provide new ideas for the development of natural functional foods. Summary of the Invention

[0007] The purpose of this invention is to provide a rapeseed pollen and maca chewable tablet for treating benign prostatic hyperplasia and its preparation method. The rapeseed pollen and maca chewable tablet provided by this invention has a positive effect on the prevention and treatment of benign prostatic hyperplasia.

[0008] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0009] This invention provides a rapeseed pollen and maca chewable tablet for treating benign prostatic hyperplasia, comprising: 25-35 parts rapeseed pollen extract, 25-35 parts maca extract, 8-12 parts binder, 5-10 parts disintegrant, 0.5-2 parts lubricant, 0.02-0.08 parts sweetener, and 35-55 parts filler.

[0010] Preferably, the method for preparing the rapeseed pollen extract includes: mixing rapeseed pollen with a eutectic solvent solution, treating with a high-voltage pulsed electric field, extracting by ultrasound, centrifuging, and drying the supernatant to obtain the rapeseed pollen extract.

[0011] More preferably, the molar ratio of choline chloride to lactic acid in the eutectic solvent solution is 1:(1.5-2.5); and the mass-to-volume ratio of rapeseed pollen to the eutectic solvent solution is 1:(18-23) g / mL.

[0012] More preferably, the electric field strength is 15-25 kV / cm, the number of pulses is 100-200, the pulse width is 10-20 μs, and the frequency is 80-120 Hz.

[0013] More preferably, the ultrasonic power is 400-500W, the temperature is 45-55℃, and the time is 15-25min.

[0014] Preferably, the preparation method of the maca extract includes: mixing maca powder with water, inoculating with compound microorganisms for anaerobic fermentation, filtering, sterilizing, and drying the filtrate to obtain the maca extract.

[0015] More preferably, the composite microorganism consists of Lactobacillus reuteri A21041 and Bifidobacterium bifidum BB-20.

[0016] More preferably, the anaerobic fermentation temperature is 35-40℃, the pH value is 5-6, and the time is 48-72h.

[0017] The present invention also provides a method for preparing rapeseed pollen and maca chewable tablets according to the above, comprising: mixing rapeseed pollen extract, maca extract and filler, adding binder to granulate, drying and granulating, adding disintegrant, lubricant and sweetener to mix, and compressing to obtain rapeseed pollen and maca chewable tablets.

[0018] The present invention also provides an application of the above-mentioned rapeseed pollen maca chewable tablets in the preparation of a drug for the prevention and treatment of benign prostatic hyperplasia.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] This invention provides a rapeseed pollen and maca chewable tablet for treating benign prostatic hyperplasia (BPH), with rapeseed pollen extract and maca extract as active ingredients. The rapeseed pollen extract is obtained by treating rapeseed pollen with a low-melting-point solvent solution under high-voltage pulsed electric field and ultrasonic extraction. The maca extract is obtained by anaerobic fermentation of maca powder by microorganisms. Specifically, the rapeseed pollen extract can inhibit 5α-reductase and reduce dihydrotestosterone production, directly targeting the core hormone target of BPH; the maca extract can regulate the endocrine axis, improve immunity and microcirculation, and alleviate the mild gastrointestinal irritation that rapeseed pollen extract may cause, thus improving the overall safety and compliance of the formulation. The rapeseed pollen extract and maca extract have a synergistic effect, significantly inhibiting BPH. Detailed Implementation

[0021] This invention provides a rapeseed pollen and maca chewable tablet for treating benign prostatic hyperplasia, comprising: 25-35 parts rapeseed pollen extract, 25-35 parts maca extract, 8-12 parts binder, 5-10 parts disintegrant, 0.5-2 parts lubricant, 0.02-0.08 parts sweetener, and 35-55 parts filler.

[0022] The excipients, binders, disintegrants, lubricants, sweeteners, and fillers involved in this invention are all selected from raw materials known in the pharmaceutical field. As a preferred embodiment, the binders include, but are not limited to, pregelatinized starch and polyvinylpyrrolidone K30; the disintegrants include, but are not limited to, sodium carboxymethyl cellulose and crospovidone; the lubricants include, but are not limited to, magnesium stearate and micronized silica; the sweeteners include, but are not limited to, steviol glycosides; and the fillers include, but are not limited to, microcrystalline cellulose, mannitol, and sorbitol.

[0023] The preferred method for preparing rapeseed pollen extract of the present invention includes: mixing rapeseed pollen with a eutectic solvent solution, treating with a high-voltage pulsed electric field, ultrasonically extracting, centrifuging, and drying the supernatant to obtain rapeseed pollen extract; the molar ratio of choline chloride to lactic acid in the eutectic solvent solution is preferably 1:(1.5-2.5), more preferably 1:2; the mass-to-volume ratio of rapeseed pollen to the eutectic solvent solution is preferably 1:(18-23) g / mL, more preferably 1:20 g / mL; the electric field... The intensity is preferably 15-25 kV / cm, more preferably 20 kV / cm; the number of pulses is preferably 100-200, more preferably 150; the pulse width is preferably 10-20 μs, more preferably 15 μs; and the frequency is preferably 80-120 Hz, more preferably 100 Hz. The ultrasonic power is preferably 400-500 W, more preferably 450 W; the temperature is preferably 45-55℃, more preferably 50℃; and the time is preferably 15-25 min, more preferably 20 min. After ultrasonic extraction, purification with macroporous adsorption resin is preferred, and more preferably, the supernatant is adsorbed onto the macroporous adsorption resin, then eluted sequentially with deionized water and a 60%-70% ethanol solution, collecting the 60%-70% ethanol eluent, and freeze-drying under vacuum to obtain rapeseed pollen extract.

[0024] The eutectic solvent of this invention can improve the solubility of lipophilic and polar active ingredients such as phytosterols and flavonoids; the high-voltage pulsed electric field can destroy the cell wall and cell membrane structure of rapeseed pollen, forming a pore effect, making it easier for the eutectic solvent to penetrate into the cell interior, accelerating the release of active ingredients, ensuring biological activity, and solving the problem of pollen itself having hard cell walls and low direct absorption rate by the human body; ultrasonic extraction promotes the diffusion of active ingredients from inside the cell to the outside, shortening the extraction time. The phytosterols in the rapeseed pollen extract prepared by the method of this invention can competitively inhibit the activity of 5α-reductase, reduce the production of dihydrotestosterone, inhibit the abnormal proliferation of prostate tissue from the source, and alleviate clinical symptoms such as urinary frequency, urgency, and difficulty in urination; the flavonoids and amino acids in the extract can reduce the chronic inflammatory response of prostate tissue, improve the local microenvironment of the prostate, protect the normal structure and function of prostate tissue, and delay the progression of hyperplasia.

[0025] The preferred method for preparing the maca extract of the present invention includes: mixing maca powder with water, inoculating with a compound microorganism for anaerobic fermentation, filtering, sterilizing, and drying the filtrate to obtain the maca extract; the compound microorganism is preferably composed of Lactobacillus reuteri A21041 and Bifidobacterium bifidum BB-20, wherein the number of Lactobacillus reuteri A21041 in the compound microorganism is preferably 400 million to 800 million CFU / g, more preferably 600 million CFU / g, and the number of Bifidobacterium bifidum BB-20 is preferably 100 million to 300 million CFU / g, more preferably 200 million CFU / g; the anaerobic fermentation temperature is preferably 35-40℃, more preferably 37℃, the pH value is preferably 5-6, more preferably 5.5, and the time is preferably 48-72h, more preferably 60h.

[0026] The two bacteria described in this invention can decompose macromolecules in maca tubers into smaller molecules, improving the water solubility and bioavailability of the extract, enhancing absorption efficiency, and degrading harmful substances such as sucralose in maca tubers through metabolism, reducing the irritation of the extract. Simultaneously, they convert precursor substances in maca into more active macamides and macaene derivatives, enhancing their endocrine-regulating and antioxidant effects. The maca extract prepared using this invention contains unique active ingredients such as macamides and macaene, which can regulate the hypothalamic-pituitary-gonadal axis, improve abnormal testosterone levels, inhibit hormone-dependent factors inducing benign prostatic hyperplasia (BPH), enhance the body's immune function, improve the prostate tissue's self-defense capabilities, and reduce the promoting effect of inflammation on BPH. The vitamin C and polyphenols in the maca extract have strong antioxidant activity, reducing oxidative stress damage to prostate cells; they can also improve local blood circulation in the prostate, increase tissue oxygen and nutrient supply, promote the excretion of metabolic waste, relieve congestion and edema of the prostate tissue, and alleviate discomfort symptoms such as frequent and painful urination.

[0027] The rapeseed pollen extract of this invention mainly targets the core hormone target of benign prostatic hyperplasia by inhibiting 5α-reductase and reducing the production of dihydrotestosterone. The maca extract, on the other hand, enhances the prevention and treatment effect by regulating the endocrine axis and improving immunity and microcirculation, addressing both the inducing factors (inflammation, oxidative stress) and accompanying symptoms (hormonal imbalance, local circulatory disorders). At the same time, the maca extract can alleviate the mild gastrointestinal irritation that rapeseed pollen extract may cause, improving the overall safety and compliance of the preparation.

[0028] The present invention also provides a method for preparing rapeseed pollen and maca chewable tablets according to the above, comprising: mixing rapeseed pollen extract, maca extract and filler, adding binder to granulate, drying and granulating, adding disintegrant, lubricant and sweetener to mix, and compressing to obtain rapeseed pollen and maca chewable tablets.

[0029] The present invention also provides an application of the above-mentioned rapeseed pollen maca chewable tablets in the preparation of a drug for the prevention and treatment of benign prostatic hyperplasia.

[0030] In this invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0031] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0032] Unless otherwise specified, the following embodiments are all conventional methods.

[0033] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0034] Rapeseed pollen was purchased from Changge Jutou Trading Co., Ltd.; maca powder was obtained by pulverizing maca tablets through a 100-mesh sieve, and the maca tablets were purchased from Bozhou Huicang Pharmaceutical Sales Co., Ltd.; pregelatinized starch was purchased from Guangzhou Jianke Biotechnology Co., Ltd.; polyvinylpyrrolidone K30 was purchased from Shandong Jinwanhua Fine Chemical Co., Ltd.; sodium carboxymethyl cellulose was purchased from Henan Puhui Biotechnology Co., Ltd.; crospovidone was purchased from Jinan Qianhe Biotechnology Co., Ltd.; microcrystalline silica gel was purchased from Jiangsu Pateze Biotechnology Co., Ltd.; microcrystalline cellulose was microcrystalline cellulose PH-102, purchased from Shaanxi Xifu Biotechnology Co., Ltd.; Lactobacillus reuteri A21041 was purchased from Guangdong Provincial Microbial Culture Collection Center, with accession number GDMCC No:62832, published in CN115948292A; Bifidobacterium bifidum BB-20 was purchased from China General Microbial Culture Collection Center, with accession number CGMCC. Patent No. 21893 is disclosed in patent CN113308420A; Lactobacillus plantarum Y388 was purchased from the China General Microbiological Culture Collection Center, with accession number CGMCC No. 21750, and is disclosed in patent CN112852684A; Bifidobacterium lactis VHProbiO20 was purchased from the China Center for Type Culture Collection, with accession number CCTCC NO:M2021598, and is disclosed in patent CN114717134A.

[0035] Example 1

[0036] (1) Preparation of rapeseed pollen extract

[0037] Choline chloride and lactic acid were mixed at a molar ratio of 1:2 and stirred at 50°C and 400 rpm for 20 min to obtain a eutectic solvent. Water with a mass of 2 times that of the eutectic solvent was added and stirred at 300 rpm for 10 min to obtain a eutectic solvent solution.

[0038] Rapeseed pollen was mixed with a eutectic solvent solution at a ratio of 1:20 g / mL. After treatment with a high-voltage pulsed electric field at an electric field strength of 20 kV / cm, 150 pulses, a pulse width of 15 μs, a frequency of 100 Hz, and a temperature of 50 ℃, the mixture was ultrasonically treated at a power of 450 W and a temperature of 50 ℃ for 20 min. After centrifugation at 4000 r / min for 12 min, the supernatant was adsorbed onto an AB-8 type macroporous adsorption resin and then eluted sequentially with deionized water and 65% ethanol solution. The 65% ethanol eluent was collected, concentrated under reduced pressure to 1 / 4 of the eluent volume, and then freeze-dried under vacuum to a water content of 3 wt%, yielding the rapeseed pollen extract.

[0039] (2) Preparation of Maca Extract

[0040] The compound microbial system consists of Lactobacillus reuteri A21041 and Bifidobacterium bifidum BB-20. The Lactobacillus reuteri A21041 has a bacterial count of 600 million CFU / g and the Bifidobacterium bifidum BB-20 has a bacterial count of 200 million CFU / g.

[0041] Maca powder and water were mixed at a mass-to-volume ratio of 1:20 g / mL. Sucrose was added to a concentration of 30 g / L, and peptone was added to a concentration of 10 g / L. The mixture was inoculated with 2% of the maca powder by weight of a compound microorganism and anaerobic fermented at 37°C and pH 5.5 for 60 h. The mixture was then filtered, sterilized, and the filtrate was freeze-dried under vacuum to a water content of 3 wt% to obtain the maca extract.

[0042] (3) Preparation of rapeseed pollen and maca chewable tablets

[0043] Accurately weigh the following ingredients according to weight: 30 parts rapeseed pollen extract, 30 parts maca extract, 10 parts pregelatinized starch, 0.5 parts polyvinylpyrrolidone K30, 3 parts sodium carboxymethyl cellulose, 3 parts crospovidone, 0.5 parts magnesium stearate, 0.3 parts micronized silica gel, 0.05 parts steviol glycosides, 15 parts sorbitol, 20 parts microcrystalline cellulose, and 15 parts mannitol.

[0044] Polyvinylpyrrolidone K30 was added to 10 times its weight volume of 65% ethanol solution and stirred at 500 rpm for 30 min to obtain a binder solution. Rapeseed pollen extract, maca extract, microcrystalline cellulose, mannitol and pregelatinized starch were mixed at 100 rpm for 15 min, and then the binder solution was added at 120 rpm to granulate. The granules were dried at 65°C to a moisture content of 2 wt% and sieved through a 17-mesh sieve. Sodium carboxymethyl cellulose, crospovidone, sorbitol and steviol glycosides were added and mixed at 120 rpm for 12 min. Magnesium stearate and micronized silica gel were added and mixed at 80 rpm for 5 min. The mixture was then compressed into tablets to obtain rapeseed pollen and maca chewable tablets.

[0045] Example 2

[0046] (1) Preparation of rapeseed pollen extract

[0047] Choline chloride and lactic acid were mixed at a molar ratio of 1:1.5 and stirred at 45°C and 300 rpm for 30 min to obtain a eutectic solvent. Water with a mass of 1.8 times that of the eutectic solvent was added and stirred at 200 rpm for 15 min to obtain a eutectic solvent solution.

[0048] Rapeseed pollen was mixed with a eutectic solvent solution at a ratio of 1:18 g / mL. After treatment with a high-voltage pulsed electric field at an electric field strength of 15 kV / cm, 100 pulses, a pulse width of 20 μs, a frequency of 80 Hz, and a temperature of 45 ℃, the mixture was ultrasonically treated at a power of 400 W and a temperature of 45 ℃ for 25 min. After centrifugation at 5000 r / min for 10 min, the supernatant was adsorbed onto an AB-8 type macroporous adsorption resin and then eluted sequentially with deionized water and 60% ethanol solution. The 60% ethanol solution eluent was collected, concentrated under reduced pressure to 1 / 3 of the eluent volume, and then freeze-dried under vacuum to a water content of 2 wt%, yielding the rapeseed pollen extract.

[0049] (2) Preparation of Maca Extract

[0050] The compound microbial system consists of Lactobacillus reuteri A21041 and Bifidobacterium bifidum BB-20. The Lactobacillus reuteri A21041 has a bacterial count of 400 million CFU / g and the Bifidobacterium bifidum BB-20 has a bacterial count of 100 million CFU / g.

[0051] Maca powder and water were mixed at a mass-to-volume ratio of 1:18 g / mL. Sucrose was added to a concentration of 25 g / L, and peptone was added to a concentration of 8 g / L. The mixture was inoculated with 3% of the maca powder by weight of a compound microorganism and anaerobic fermented at 35°C and pH 5 for 72 h. The mixture was then filtered, sterilized, and the filtrate was freeze-dried under vacuum to a water content of 3 wt% to obtain the maca extract.

[0052] (3) Preparation of rapeseed pollen and maca chewable tablets

[0053] Accurately weigh the following ingredients according to weight: 25 parts rapeseed pollen extract, 35 parts maca extract, 8 parts pregelatinized starch, 1 part polyvinylpyrrolidone K30, 2 parts sodium carboxymethyl cellulose, 4 parts crospovidone, 0.3 parts magnesium stearate, 0.2 parts micronized silica gel, 0.03 parts steviol glycosides, 10 parts sorbitol, 15 parts microcrystalline cellulose, and 13 parts mannitol.

[0054] Polyvinylpyrrolidone K30 was added to 8 times its weight volume of 70% ethanol solution and stirred at 450 rpm for 35 min to obtain a binder solution. Rapeseed pollen extract, maca extract, microcrystalline cellulose, mannitol and pregelatinized starch were mixed at 80 rpm for 12 min, and then the binder solution was added at 100 rpm to granulate. The granules were dried at 60℃ to a moisture content of 3 wt% and sieved through a 17-mesh sieve. Sodium carboxymethyl cellulose, crospovidone, sorbitol and steviol glycosides were added and mixed at 100 rpm for 10 min. Magnesium stearate and micronized silica gel were added and mixed at 50 rpm for 8 min. The mixture was then compressed into tablets to obtain rapeseed pollen and maca chewable tablets.

[0055] Example 3

[0056] (1) Preparation of rapeseed pollen extract

[0057] Choline chloride and lactic acid were mixed at a molar ratio of 1:2.5 and stirred at 55°C and 500 rpm for 15 min to obtain a eutectic solvent. Water with a mass of 2.5 times that of the eutectic solvent was added and stirred at 400 rpm for 8 min to obtain a eutectic solvent solution.

[0058] Rapeseed pollen was mixed with a eutectic solvent solution at a ratio of 1:23 g / mL. After treatment with a high-voltage pulsed electric field at an electric field strength of 25 kV / cm, 200 pulses, a pulse width of 10 μs, a frequency of 120 Hz, and a temperature of 55 ℃, the mixture was ultrasonically treated for 15 min at a power of 500 W and a temperature of 55 ℃. The mixture was then centrifuged at 3000 r / min for 15 min. The supernatant was adsorbed onto an AB-8 type macroporous adsorption resin and eluted sequentially with deionized water and 70% ethanol solution. The 70% ethanol eluent was collected, concentrated under reduced pressure to 1 / 5 of the eluent volume, and then freeze-dried under vacuum to a water content of 4 wt%, yielding the rapeseed pollen extract.

[0059] (2) Preparation of Maca Extract

[0060] The compound microbial system consists of Lactobacillus reuteri A21041 and Bifidobacterium bifidum BB-20. The Lactobacillus reuteri A21041 has a bacterial count of 800 million CFU / g and the Bifidobacterium bifidum BB-20 has a bacterial count of 300 million CFU / g.

[0061] Maca powder and water were mixed at a mass-to-volume ratio of 1:23 g / mL. Sucrose was added to a concentration of 35 g / L, and peptone was added to a concentration of 12 g / L. The mixture was inoculated with 1% of the maca powder by weight of a compound microorganism and anaerobic fermented at 40°C and pH 6 for 48 h. The mixture was then filtered, sterilized, and the filtrate was freeze-dried under vacuum to a water content of 3 wt% to obtain the maca extract.

[0062] (3) Preparation of rapeseed pollen and maca chewable tablets

[0063] Accurately weigh the following ingredients according to weight: 35 parts rapeseed pollen extract, 25 parts maca extract, 12 parts pregelatinized starch, 1.5 parts polyvinylpyrrolidone K30, 5 parts sodium carboxymethyl cellulose, 5 parts crospovidone, 0.8 parts magnesium stearate, 0.5 parts micronized silica gel, 0.08 parts steviol glycosides, 10 parts sorbitol, 22 parts microcrystalline cellulose, and 18 parts mannitol.

[0064] Polyvinylpyrrolidone K30 was added to 12 times its weight volume of 60% ethanol solution and stirred at 550 rpm for 28 min to obtain a binder solution. Rapeseed pollen extract, maca extract, microcrystalline cellulose, mannitol and pregelatinized starch were mixed at 120 rpm for 12 min, and then the binder solution was added at 150 rpm to granulate. The granules were dried at 70°C to a moisture content of 3 wt% and sieved through an 18-mesh sieve. Sodium carboxymethyl cellulose, crospovidone, sorbitol and steviol glycosides were added and mixed at 150 rpm for 10 min. Magnesium stearate and micronized silica gel were added and mixed at 100 rpm for 3 min. The mixture was then compressed into tablets to obtain rapeseed pollen and maca chewable tablets.

[0065] Comparative Example 1

[0066] The difference from Example 1 is that “30 parts of rapeseed pollen extract and 30 parts of maca extract” are replaced with “60 parts of rapeseed pollen extract” and step (2) is deleted.

[0067] Comparative Example 2

[0068] The difference from Example 1 is that “30 parts rapeseed pollen extract and 30 parts maca extract” are replaced with “60 parts maca extract” and step (1) is deleted.

[0069] Comparative Example 3

[0070] The difference from Example 1 is that the eutectic solvent solution in step (1) is replaced with a 70% ethanol solution by volume.

[0071] Comparative Example 4

[0072] The difference from Example 1 is that the preparation method of rapeseed pollen extract in step (1) is as follows: rapeseed pollen is placed in a supercritical extraction vessel, and the extraction pressure is 30 MPa, the temperature is 60 °C, the CO2 flow rate is 15 g / min, and the extract is collected from the separation vessel to obtain rapeseed pollen extract.

[0073] Comparative Example 5

[0074] Unlike Example 1, the composite microorganism in step (2) is composed of Lactobacillus plantarum Y388 and Bifidobacterium lactis VHProbiO20. The number of Lactobacillus plantarum Y388 in the composite microorganism is 600 million / g and the number of Bifidobacterium lactis VHProbiO20 is 200 million / g. The fermentation conditions remain unchanged.

[0075] Comparative Example 6

[0076] The difference from Example 1 is that the preparation method of maca extract in step (2) is as follows: maca powder and 70% ethanol solution are mixed at a mass-volume ratio of 1:20 g / mL, and ultrasonically extracted twice at a power of 400W and a temperature of 55℃ for 20 min each time. After centrifugation at 5000 r / min for 10 min, the supernatant is freeze-dried under vacuum to a water content of 3 wt% to obtain maca extract.

[0077] Experimental Example 1

[0078] SPF-grade male SD rats weighing 180-220g were selected and acclimatized for one week under conditions of 22-25℃ temperature, 45-55% relative humidity, and 12h light / dark alternation.

[0079] (1) Group modeling and drug administration

[0080] After adaptive feeding, the rats were divided into 12 groups (blank group, model group, positive group and experimental group (Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, Comparative Example 5 group and Comparative Example 6 group)) with 10 rats in each group.

[0081] After anesthetizing each group of rats with an intraperitoneal injection of 1% sodium pentobarbital at a dose of 40 mg / kg, the abdomen was shaved and disinfected. Except for the control group, the rats in the other groups underwent bilateral orchiectomy under sterile conditions. In the control group, only the skin was cut open without removing the testes.

[0082] Starting 7 days after surgery, except for the control group, rats in other groups were injected subcutaneously into the back of the rats with testosterone propionate at a dose of 5 mg / kg, once a day for 14 consecutive days; rats in the control group were injected subcutaneously into the back of the rats with an equal volume of physiological saline.

[0083] On day 15 of the injection, the administration regimens for each group were as shown in Table 1. The administration lasted for 30 days. Except for the control group, rats in other groups were injected subcutaneously with testosterone propionate solution at a dose of 5 mg / kg on the back of the rats every 2 days. The control group was injected with an equal volume of physiological saline every 2 days. The administration was performed by gavage first, followed by injection, for a total of 30 days.

[0084] The preparation method of the chewable tablet suspension is as follows: after grinding the rapeseed pollen maca chewable tablets into powder, use 0.5% sodium carboxymethyl cellulose (CMC-Na) solution to prepare a chewable tablet suspension with a concentration of 10 mg / mL (each mL contains 10 mg of chewable tablet powder) for later use.

[0085] Table 1. Administration methods for each group

[0086]

[0087]

[0088] (2) Measurement of serum physiological indicators

[0089] After the last administration, rats in each group were anesthetized by intraperitoneal injection of 1% sodium pentobarbital at a dose of 40 mg / kg. Blood was collected from the eyeballs, placed in centrifuge tubes, and allowed to stand at room temperature for 30 minutes. Then, the tubes were centrifuged at 3000 r / min for 15 minutes to obtain serum.

[0090] The concentration of dihydrotestosterone (DHT) in serum was measured according to the instructions of the rat dihydrotestosterone (DHT) ELISA kit ml002998, and the concentration of estradiol in serum was measured according to the instructions of the rat estradiol (E2) ELISA kit ml002871. The specific results are shown in Table 2.

[0091] Table 2 Serum dihydrotestosterone and estradiol concentrations in rats of each group

[0092] Grouping Dihydrotestosterone (nmol / L) Estradiol (pmol / L) Blank group 4.24 8.36 Model group 5.81 12.48 positive group 4.69 8.74 Example 1 Group 4.77 8.82 Example 2 group 4.82 8.87 Example 3 Group 4.85 8.90 Comparative Example 1 5.40 10.29 Comparative Example 2 5.38 10.58 Comparative Example 3 Groups 5.16 9.71 Comparative Example 4 Groups 5.24 9.40 Comparative Example 5 Groups 5.03 9.35 Comparative Example 6 Groups 5.17 9.53

[0093] As shown in Table 2, the concentrations of dihydrotestosterone (DHT) and estradiol in the model group were significantly higher than those in the control group, indicating the successful establishment of the benign prostatic hyperplasia (BPH) animal model. The DHT and estradiol concentrations in the positive control group were close to those in the control group and significantly lower than those in the model group, verifying that finasteride can effectively block the conversion of testosterone to DHT, inhibiting BPH at its hormonal source, consistent with known clinical effects. The DHT and estradiol concentrations in the Examples 1-3 groups were close to those in the positive control group and significantly lower than those in the model group, indicating that the rapeseed pollen and maca chewable tablets prepared in this invention have the ability to regulate sex hormone levels comparable to the chemical drug finasteride. A comparison of the data from Comparative Examples 1-2 and Example 1 shows that rapeseed pollen extract and maca extract have a synergistic effect in inhibiting DHT production and regulating estrogen, while the effect of a single component is limited. A comparison of the data from Comparative Examples 3-4 and Example 1 shows that the extraction process using a low-melting-point solvent combined with a high-voltage pulsed electric field is crucial for fully extracting the active ingredients from rapeseed pollen. Traditional solvents or methods cannot effectively break down cell walls and extract the active ingredients, leading to reduced product efficacy. Comparison of data from Comparative Examples 5-6 and Example 1 shows that the specific compound microbial fermentation process (Lactobacillus reuteri A21041 and Bifidobacterium bifidum BB-20) is crucial for converting precursor substances in maca, generating highly active macaamides and macaenes, and reducing irritation. Ethanol solvent extraction cannot achieve the same effect.

[0094] (3) Measurement of prostate index

[0095] After blood collection, the rats were quickly dissected, and the prostate tissue (including the ventral, dorsal, and lateral lobes) was completely separated and removed. The tissue was rinsed with pre-cooled physiological saline, the surface moisture was blotted dry with filter paper, the wet weight of the prostate was measured with an electronic balance, and the prostate index was calculated (prostate index (mg / g) = wet weight of prostate / body weight of rat). The specific results are shown in Table 3.

[0096] Table 3 Prostate index of rats in each group

[0097] Grouping Prostate index (mg / g) Grouping Prostate index (mg / g) Blank group 0.87 Comparative Example 1 2.53 Model group 3.39 Comparative Example 2 2.66 positive group 1.74 Comparative Example 3 Groups 2.30 Example 1 Group 1.82 Comparative Example 4 Groups 2.48 Example 2 group 1.87 Comparative Example 5 Groups 2.25 Example 3 Group 1.91 Comparative Example 6 Groups 2.36

[0098] As shown in Table 3, the prostate index in the model group was significantly higher than that in the control group, further confirming the successful modeling. The index in the positive group was significantly lower than that in the model group, demonstrating the effectiveness of finasteride. The prostate index in Examples 1-3 was comparable to that in the positive group and significantly lower than that in the model group, indicating that the chewable tablets of this invention can not only regulate hormone levels but also substantially inhibit the pathological hyperplasia of prostate tissue, with a very significant effect. A comparison of the data from Comparative Examples 1-2 and Example 1 shows that the best therapeutic effect can only be achieved by using rapeseed pollen extract and maca extract in combination; a single component can only partially alleviate hyperplasia. A comparison of the data from Comparative Examples 3-6 and Example 1 shows that different solvents and extraction methods affect the extraction of the active ingredients, thereby affecting the prostate index.

[0099] In summary, the rapeseed pollen and maca chewable tablets provided by this invention exhibit effects comparable to the positive-positive chemical drug finasteride in reducing serum dihydrotestosterone (DHT) concentration, regulating estrogen levels, and reducing prostate weight, indicating a good anti-benign prostatic hyperplasia (BPH) effect. A significant synergistic effect exists between rapeseed pollen extract and maca extract, preventing and treating BPH through multiple pathways and targets via a dual mechanism of inhibiting DHT production and regulating overall hormonal balance and immunity. The eutectic solvent-high-voltage pulsed electric field extraction process for rapeseed pollen and the specific compound microbial fermentation process for maca are key technologies ensuring product efficacy. These processes maximize the extraction and conversion of active ingredients, which cannot be replaced by traditional or alternative methods.

[0100] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A rapeseed pollen and maca chewable tablet for treating benign prostatic hyperplasia, characterized in that, include: 25-35 parts rapeseed pollen extract, 25-35 parts maca extract, 8-12 parts binder, 5-10 parts disintegrant, 0.5-2 parts lubricant, 0.02-0.08 parts sweetener, and 35-55 parts filler.

2. The rapeseed pollen and maca chewable tablets according to claim 1, characterized in that, The preparation method of the rapeseed pollen extract includes: mixing rapeseed pollen with a eutectic solvent solution, treating it with a high-voltage pulsed electric field, extracting it with ultrasound, centrifuging it, and drying the supernatant to obtain the rapeseed pollen extract.

3. The rapeseed pollen and maca chewable tablets according to claim 2, characterized in that, The molar ratio of choline chloride to lactic acid in the eutectic solvent solution is 1:(1.5-2.5); the mass-to-volume ratio of rapeseed pollen to the eutectic solvent solution is 1:(18-23) g / mL.

4. The rapeseed pollen and maca chewable tablets according to claim 2, characterized in that, The electric field strength is 15-25 kV / cm, the number of pulses is 100-200, the pulse width is 10-20 μs, and the frequency is 80-120 Hz.

5. The rapeseed pollen and maca chewable tablets according to claim 2, characterized in that, The ultrasound power is 400-500W, the temperature is 45-55℃, and the time is 15-25min.

6. The rapeseed pollen and maca chewable tablets according to claim 1, characterized in that, The preparation method of the maca extract includes: mixing maca powder with water, inoculating with compound microorganisms for anaerobic fermentation, filtering, sterilizing, and drying the filtrate to obtain maca extract.

7. The rapeseed pollen and maca chewable tablets according to claim 6, characterized in that, The composite microorganism consists of Lactobacillus reuteri A21041 and Bifidobacterium bifidum BB-20.

8. The rapeseed pollen and maca chewable tablets according to claim 6, characterized in that, The anaerobic fermentation was carried out at a temperature of 35-40℃, a pH of 5-6, and a time of 48-72 hours.

9. A method for preparing rapeseed pollen and maca chewable tablets according to any one of claims 1-8, characterized in that, include: Rapeseed pollen extract, maca extract and filler are mixed, binder is added and granulated, dried and granulated, disintegrant, lubricant and sweetener are added and mixed, and tablets are compressed to obtain rapeseed pollen and maca chewable tablets.

10. The use of the rapeseed pollen and maca chewable tablets according to any one of claims 1-8 in the preparation of a drug for preventing and treating benign prostatic hyperplasia.

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