Traditional Chinese medicine formula for treating male impotence and premature ejaculation

Abstract

The invention relates to the field of traditional Chinese medicine preparations, and discloses a traditional Chinese medicine formula for treating male impotence and premature ejaculation. Comprising 5-30 parts of ginseng, 3-25 parts of cornu cervi pantotrichum, 2-15 parts of penis cervi, 3-20 parts of prepared radix morindae officinalis, 4-25 parts of herba epimedii, 2-18 parts of herba cistanche, 1-10 parts of fructus psoraleae marrow, 2-12 parts of fried semen euryales, 3-18 parts of fructus lycii, 1-8 parts of lotus seeds, 0.5-5 parts of lotus stamen, 2-15 parts of charred eucommia ulmoides, 0.5-6 parts of star anise, 0.3-4 parts of fennel, 1-9 parts of semen allii tuberosi, 2-15 parts of poria cocos, 1-10 parts of rhizoma alismatis, 0.1-3 parts of halite, 1-12 parts of cortex phellodendri, 0.5-8 parts of radix achyranthis bidentatae and 0.5-5 parts of Wedelia chinensis. According to the invention, through a refined formula design and an auxiliary material optimization strategy, the solvent residue and the impurity content are reduced, the medicine purity is improved, and the adverse reaction is effectively reduced.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a traditional Chinese medicine formula for treating male impotence and premature ejaculation. Background Art

[0002] In the field of pharmaceutical preparations, the extraction of active ingredients, stability control, drug release regulation and safety optimization are important research directions for preparation research and development. However, the existing technology still has many deficiencies in the above aspects, which affects the clinical efficacy of drugs and patient compliance.

[0003] First, in terms of active ingredient extraction, traditional methods mainly include water decoction, alcohol extraction, mechanical crushing, etc. These methods may cause degradation of some heat-sensitive components due to high temperature or the use of chemical reagents during the extraction process, thereby reducing the efficacy. At the same time, although mechanical crushing can improve the efficiency of cell disruption, due to the lack of selectivity, the purity of the extracted active ingredients is low and there are many impurities, which affects the stability of subsequent preparations. Although some solvent extraction methods can increase the solubility of specific ingredients, they are often accompanied by the risk of solvent residues, increasing safety hazards. Therefore, how to improve the extraction rate of active ingredients while reducing impurity interference and solvent residues is a key issue in the optimization of formulation technology.

[0004] Secondly, in terms of drug stability and bioavailability, in the prior art, many active ingredients are difficult to be fully absorbed in the body or are easily degraded during storage due to their low solubility and poor chemical stability. For example, some natural drug ingredients are prone to oxidation or hydrolysis under the influence of oxygen, humidity or light, resulting in reduced efficacy. The traditional method of powder mixing or direct capsule filling cannot effectively protect the active ingredients, and the drug absorption rate is low. In addition, some poorly soluble drugs have a slow dissolution rate in the body, resulting in low bioavailability, which affects their therapeutic effect. Therefore, it is urgent to develop a formulation technology that can improve drug stability and enhance bioavailability to ensure efficient absorption and stable function of drugs in the body.

[0005] Furthermore, in terms of drug release characteristics, existing rapid-release preparations often have the problem of too-fast drug release, which causes a sharp increase in blood drug concentration in a short period of time, which may cause a burst effect and increase the risk of side effects. At the same time, due to the rapid decrease in blood drug concentration, patients need to take the drug frequently, which affects compliance. Ordinary sustained-release preparations have the problem of inaccurate release control, resulting in unstable drug efficacy. Therefore, how to optimize the sustained-release characteristics of the drug while ensuring the drug efficacy so that it can be released more smoothly and continuously is an urgent problem to be solved in current formulation technology.

[0006] Therefore, the present invention proposes a Chinese medicine formula for treating male impotence and premature ejaculation to solve the deficiencies of the prior art. Summary of the invention

[0007] In view of the shortcomings of the prior art, the present invention provides a Chinese medicine formula for treating male impotence and premature ejaculation, which uses liquid nitrogen wall breaking and supercritical CO 2 The combination of extraction technology significantly improves the extraction efficiency of active ingredients, ensures the high purity of effective ingredients, and avoids high temperature damage and solvent residue problems. At the same time, the present invention improves the stability and bioavailability of drugs through β-cyclodextrin inclusion technology and nano drug delivery technology, ensuring that the drugs can be efficiently absorbed in the body and prolonging the duration of drug effect. In addition, the present invention also successfully improves the sustained-release characteristics of drugs through the optimization of gradient drying process and nano sustained-release carriers, achieves stable release of drugs, avoids burst release effect, reduces the frequency of patients taking medicine, and improves treatment compliance. Through these innovative technologies, the present invention solves the problems of low extraction rate, poor drug stability, poor sustained-release effect, etc. in traditional treatment methods, and significantly improves the efficacy and safety of drugs.

[0008] To achieve the above objectives, the present invention is implemented through the following technical scheme: a traditional Chinese medicine formula for treating male impotence and premature ejaculation, comprising the following components in parts by mass: 5-30 parts of ginseng, 3-25 parts of pilose antler, 2-15 parts of deer whip, 3-20 parts of processed Morinda officinalis, 4-25 parts of epimedium, 2-18 parts of Cistanche deserticola, 1-10 parts of bone marrow supplement, 2-12 parts of stir-fried Euryale ferox, 3-18 parts of wolfberry, 1-8 parts of lotus seeds, 0.5-5 parts of lotus stamens, 2-15 parts of Eucommia ulmoides charcoal, 0.5-6 parts of star anise, 0.3-4 parts of fennel, 1-9 parts of leek seeds, 2-15 parts of Poria, 1-10 parts of Alisma orientalis, 0.1-3 parts of isatis salt, 1-12 parts of Phellodendron chinense, 0.5-8 parts of Achyranthes bidentata, 1-8 parts of Cephalotaxus chinensis, and 0.5-5 parts of Herba Rejuvenati.

[0009] Preferably, the mass ratio of ginseng, pilose antler and epimedium is 1:0.3-0.7:0.4-0.9, and the bone marrow supplement accounts for 8-15% of the mass of Eucommia ulmoides charcoal.

[0010] Preferably, a traditional Chinese medicine formula for treating male impotence and premature ejaculation also includes 0.5-4 parts of β-cyclodextrin and 1-6 parts of hydroxypropyl methylcellulose, and the mass ratio of β-cyclodextrin to total flavonoids is 1:3-1:8.

[0011] Preferably, a method for preparing a traditional Chinese medicine formula for treating male impotence and premature ejaculation comprises the following steps: S1. Wall breaking and activation: freeze the antlers and penises with liquid nitrogen to -60--80°C and break them into 0.5-2 mm particles; Liquid nitrogen quick freezing can instantly destroy the ice crystal structure of the cell wall and retain heat-sensitive active ingredients (such as antler peptides); after crushing, the particles increase the specific surface area and improve the subsequent extraction efficiency.

[0012] S2, step extraction: ginseng and epimedium are first extracted with supercritical CO 2Extraction, followed by reflux extraction with 50-70% ethanol; Supercritical CO 2 Fat-soluble components (such as ginsenosides) are preferentially extracted, and the entrainer mixed system (ethyl acetate-acetone) enhances the solubility of polar components; ethanol reflux further extracts water-soluble substances.

[0013] S3, low temperature enzymatic hydrolysis: react the S1 treated material with protease at 35-55°C for 1.5-4 h, with the added amount of protease being 1200-2500 U / g; Pancreatic enzymes directionally cleave collagen (antler) to release active peptides; flavor enzymes degrade the fiber matrix and increase the dissolution of small molecules; ultrasonic cavitation effect accelerates enzyme-substrate contact.

[0014] S4, nano-reconstruction: the extracts of Phellodendron amurense and Poria cocos were encapsulated with ZIF-8 carrier at pH 5.6-6.4; The pore size of ZIF-8 (0.8-1.5 nm) is suitable for icariin (molecular size ≈ 1.2 nm), which binds to Zn through coordination bonds. 2+ Combined to achieve high load; S5, gradient drying: adjust the humidity in stages from 60% to 15%, and increase the temperature from 45℃ to 70℃.

[0015] Preferably, in the S2 step, supercritical CO 2 The extraction pressure is 28-35 MPa, the entrainer is a mixture of ethyl acetate and acetone, the volume ratio of the two is 1:2-1:4, and the total addition amount is 9-13%.

[0016] Preferably, the protease in step S3 is a composite enzyme system composed of trypsin and flavor protease at an activity ratio of 3:1-5:1, and 20-40 kHz ultrasonic treatment is applied simultaneously during enzymatic hydrolysis.

[0017] Preferably, the synthesis conditions of the ZIF-8 carrier in step S4 are: The zinc nitrate concentration is 0.18-0.28 mol / L, the 2-methylimidazole concentration is 0.25-0.45 mol / L, the crystallization temperature is 80-120°C, and the drug loading time is 12-24 h.

[0018] Preferably, the ZIF-8 carrier has an embedding efficiency of 65-85%, an average pore size of 0.8-1.5 nm, and a BET specific surface area of ​​≥300 m 2 / g; the XRD spectrum of the ZIF-8 carrier has characteristic diffraction peaks at 2θ of 7.3±0.2°, 12.7±0.3°, and 18.1±0.3°.

[0019] The pore size of ZIF-8 (0.8-1.5 nm) is suitable for icariin (molecular size ≈ 1.2 nm), which binds to Zn through coordination bonds. 2+ Combined to achieve high load; The characteristic XRD peaks (2θ=7.3°, 12.7°, 18.1°) prove the integrity of the MOFs crystal structure and ensure the stability of drug sustained release.

[0020] Preferably, the parameters of the staged drying in step S5 are: In the first stage, the humidity is 60±5% and the temperature is 45±2℃ for 30-60 min; The second stage is maintained at 30±5% humidity and 60±3℃ for 40-90 min; The third stage is maintained at 15±3% humidity and 70±2℃ for 20-50 min; The first stage (60% humidity) prevents oxidation of heat-sensitive components; the second stage (30% humidity) accelerates moisture diffusion; and the third stage (15% humidity) avoids high-temperature carbonization.

[0021] Preferably, a Chinese medicine composition, wherein the content of icariin in the composition is ≥2.8 mg / g, ginsenoside Rg1+Rb1 is ≥3.5 mg / g, berberine is ≥1.2 mg / g, and echinacoside is ≥0.8 mg / g; Ginsenosides (Rg1+Rb1) ≥ 3.5 mg / g: Activates eNOS phosphorylation and promotes NO production (endothelial cell signaling).

[0022] Berberine ≥1.2 mg / g: Inhibits α1-adrenergic receptors and lowers the ejaculation threshold (neurotransmitter regulation).

[0023] Echinacoside ≥ 0.8 mg / g: mediates prostate smooth muscle relaxation via ERβ receptors (hormone receptor regulation).

[0024] The present invention provides a Chinese medicine formula for treating male impotence and premature ejaculation. It has the following beneficial effects: 1. The present invention uses liquid nitrogen to break the wall and supercritical CO 2 The cell walls of medicinal materials are broken quickly under low temperature conditions to increase the release rate of active ingredients, and supercritical CO 2 The target ingredients are accurately extracted to avoid high temperature oxidation and solvent residue. Compared with the traditional water decoction or mechanical crushing extraction method, the present invention significantly improves the extraction rate and purity of active ingredients, reduces impurity interference, and increases the drug concentration.

[0025] 2. The present invention adopts β-cyclodextrin inclusion and nano drug loading technology to effectively improve drug stability, prevent oxidative decomposition of active ingredients, and improve their solubility in the aqueous phase, making them more easily absorbed by the body. Compared with traditional powder mixing or ordinary capsule filling methods, the present invention reduces the degradation rate of drugs during storage and transportation, improves bioavailability, and thus enhances the therapeutic effect of drugs.

[0026] 3. The present invention combines gradient drying technology with nano sustained-release carriers to ensure a more stable sustained-release effect of the drug and prolong the duration of the drug effect. Compared with traditional rapid-release preparations, the present invention can regulate the drug release rate, reduce the peak-to-valley fluctuation of blood drug concentration, avoid the sudden release effect, reduce the frequency of drug administration, improve patient compliance, and enhance the therapeutic effect.

[0027] 4. Through refined formula design and excipient optimization strategy, the present invention reduces solvent residue and impurity content, improves drug purity, and effectively reduces adverse reactions. Compared with traditional solvent extraction or high-temperature drying methods, the present invention avoids the toxicity risk caused by solvent residues, while optimizing drug delivery, reducing adverse reactions caused by local excessive concentrations, and making medication safer and more reliable for patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The present invention is a flow chart of the preparation method of a traditional Chinese medicine formula for treating male impotence and premature ejaculation. DETAILED DESCRIPTION

[0029] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] Please see attached Figure 1 : Example 1 Formula composition (mass parts): Preparation process: Broken cell activation The antlers and penises were placed in a liquid nitrogen quick-freezing device, cooled to -75°C, maintained for 30 minutes, and then mechanically crushed to obtain particles with a particle size of 0.8-1.2 mm.

[0031] Supercritical CO 2 extraction Ginseng and epimedium were put into supercritical extraction equipment with a set pressure of 32 MPa. The entrainers were ethyl acetate and acetone (volume ratio 1:3), the total addition amount was 12%, and the extraction time was 2 hours.

[0032] Low temperature enzymatic hydrolysis The broken material was mixed with a trypsin-flavor protease complex enzyme system (activity ratio 4:1) at an addition amount of 1800 U / g, and reacted at 38°C and 30 kHz ultrasonic assistance for 3 hours.

[0033] Nano drug delivery The extracts of Phellodendron amurense and Poria cocos were mixed with the ZIF-8 carrier, the pH was adjusted to 6.0, the zinc nitrate concentration was 0.22 mol / L, the 2-methylimidazole concentration was 0.35 mol / L, the crystallization temperature was 110°C, and the loading time was 18 hours.

[0034] Gradient drying Stage 1: Humidity 60±2%, temperature 45±1℃, maintain for 50 minutes; Stage 2: Humidity 30±2%, temperature 60±1℃, maintain for 70 minutes; Stage 3: Humidity 15±1%, temperature 70±1℃, maintain for 40 minutes Example 2 Formula composition (mass parts): Add on the basis of the formula of Example 1: β-cyclodextrin: 2.5 parts Hydroxypropyl methylcellulose: 4 parts β-cyclodextrin to total flavonoids mass ratio: 1:5 Process adjustment: Excipient pretreatment β-cyclodextrin and epimedium extract were mixed according to a certain proportion and stirred at 40° C. for 2 hours to form an inclusion complex.

[0035] Nano drug delivery optimization The inclusion complex was loaded together with the ZIF-8 carrier, and the other parameters were the same as in Example 1.

[0036] Example 3 Formula composition (mass parts): Preparation process: Broken cell activation The antlers and penises were placed in a liquid nitrogen quick-freezing device, cooled to -80°C and maintained for 45 minutes, and then processed using a low-temperature impact crusher to obtain uniform particles with a particle size of 0.5-0.8 mm.

[0037] Supercritical CO 2 extraction Ginseng and epimedium were put into a supercritical extraction kettle with a set pressure of 35 MPa. The entrainers were ethyl acetate and acetone (volume ratio 1:2) with a total addition amount of 13%. Dynamic circulation extraction was performed for 3 hours.

[0038] Low temperature enzymatic hydrolysis The cell wall-broken material was mixed with a trypsin-flavor protease complex enzyme system (activity ratio 5:1) at an addition amount of 2500 U / g and reacted at 55°C and 40 kHz ultrasonic assistance for 4 hours.

[0039] Nano drug delivery Phellodendron amurense and Poria cocos extracts were mixed with the ZIF-8 carrier, the pH was adjusted to 5.6, the zinc nitrate concentration was 0.28 mol / L, the 2-methylimidazole concentration was 0.45 mol / L, the crystallization temperature was 120°C, and the loading time was 24 hours. Carrier parameters: average pore size 0.8 nm, BET specific surface area 412 m 2 / g.

[0040] Gradient drying Stage 1: Humidity 60±2%, temperature 45±1℃, maintain for 60 minutes; Stage 2: Humidity 30±2%, temperature 60±1℃, maintain for 90 minutes; The third stage: humidity 15±1%, temperature 70±1℃, maintain for 50 minutes.

[0041] Comparative Example: Comparative Example 1: Formula composition (mass parts): Preparation process: Wall breaking process: After drying the velvet antler and deer penis with 60° C. hot air for 48 hours, a conventional pulverizer was used to pulverize the medicinal materials into 2-3 mm particles (different from Example 1, liquid nitrogen wall breaking was not used).

[0042] Traditional extraction: Add the crushed medicinal materials and 10 times the amount of water into the extractor, use the conventional boiling method, the first round of boiling is 30 minutes, the second round of boiling is 45 minutes, and the filtrate is combined.

[0043] Drying process: The extracted extract was dried at a constant temperature of 70°C until the residual moisture was <8% (different from Example 1, no gradient drying process was used).

[0044] Comparative Example 2: Formula composition (mass parts): Preparation process: Wall breaking process: The antlers and deer penis are crushed into 3-4 mm particles using a conventional grinder without using liquid nitrogen to break the wall.

[0045] Supercritical CO 2Extraction: Ginseng, epimedium and ethyl acetate:acetone (volume ratio 1:3) were used as entrainers and supercritical CO 2 The extraction pressure was set to 28 MPa and the extraction time was 2 hours (compared to 32 MPa and 12% addition amount in Example 1).

[0046] Nano drug delivery: chitosan microspheres were used as carriers. During the preparation of the drug delivery, β-cyclodextrin was not used, and only the traditional hydration preparation method was used (different from Example 2, the auxiliary material β-cyclodextrin was not used for inclusion).

[0047] Drying process: The extract is dried at a constant temperature of 70°C to reduce the loss of active ingredients in the medicinal materials. Comparative Example 3: Formula composition (mass parts): Preparation process: Wall breaking process: The velvet antler and deer penis were quickly frozen to -80°C with liquid nitrogen and broken into 0.5-0.8 mm particles (consistent with Example 3).

[0048] Supercritical CO 2 Extraction: Supercritical CO 2 The extraction pressure was set to 35 MPa, the entrainer was ethyl acetate:acetone (volume ratio 1:2), the addition amount was 13%, and the extraction time was 3 hours (the same as Example 3).

[0049] Low temperature enzymatic hydrolysis: a trypsin-flavor protease complex enzyme system (activity ratio 5:1) was used, and the reaction was carried out at 55°C and 40 kHz ultrasound assistance for 4 hours (consistent with Example 3).

[0050] Nano drug delivery: using ZIF-8 carrier, adjusting pH to 5.6, zinc nitrate concentration to 0.28 mol / L, 2-methylimidazole concentration to 0.45 mol / L, crystallization temperature to 120°C, loading time to 24 hours (consistent with Example 3).

[0051] Drying process: The concentrate is dried in a single stage at a constant temperature of 70°C until the residual moisture is <8% (different from the gradient drying in Example 3).

[0052] Test experiment: Experimental objectives: Verify the innovativeness of the formula of the present invention and its comprehensive advantages in practical applications, especially how the synergistic effect of the formula and process can improve the extraction efficiency, ingredient stability, drug release and bioavailability of the active ingredients, and demonstrate significant differences from the existing technology.

[0053] Experimental Materials: Main medicinal materials: ginseng, pilose antler, deer penis, processed Morinda officinalis, epimedium, Cistanche deserticola, bone marrow tonic, stir-fried Euryale ferox, wolfberry, lotus seeds, lotus stamens, Eucommia ulmoides charcoal, star anise, fennel, leek seeds, Poria cocos, Alisma orientalis, isatral salt, Phellodendron chinense, Achyranthes bidentata, Coptis chinensis, and Herba Rejuvenati.

[0054] Excipients: β-cyclodextrin, hydroxypropyl methylcellulose, 2-methylimidazole, zinc nitrate, chitosan, etc.

[0055] Experimental equipment: Supercritical CO 2 Extraction Instrument Liquid nitrogen wall breaking machine Ultrasonic Cleaner HPLC (High Performance Liquid Chromatography) Analyzer Dynamic Light Scattering (DLS) LC-MS / MS (Liquid Chromatography-Mass Spectrometry) Instruments Constant temperature dissolution test equipment Experimental groups: Experimental group: Example 1, Example 2, Example 3 (using the innovative formula and process of the present invention) Comparative group: Comparative Example 1 (traditional cell wall breaking and extraction process), Comparative Example 2 (formulation without auxiliary materials), Comparative Example 3 (unoptimized single-stage drying process) Experiment 1: Extraction efficiency and ingredient synergistic effect test Experimental objectives: Verify the liquid nitrogen wall breaking and supercritical CO 2 The role of extraction and other technologies in improving the efficiency of extracting active ingredients, with particular attention paid to the synergistic effects of ginseng, deer antler and epimedium in the formula.

[0056] Experimental steps: Preparation of medicinal materials: According to the formula ratio of the embodiment and the comparison group, each group of medicinal materials was weighed.

[0057] The example group used liquid nitrogen wall breaking technology (frozen at -75°C and then mechanically broken into 0.8-1.2 mm particles), and the control group used conventional crushing.

[0058] Extraction process: Example 1 Using supercritical CO 2 Extraction, pressure 32 MPa, extraction time 2 h, ethyl acetate and acetone (volume ratio 1:3) as entrainers, total addition amount 12%.

[0059] The control group used the traditional water decoction method, boiling 10 times the water twice, each time for 45 minutes, and the filtrates were combined and concentrated.

[0060] Component Analysis: The content of the main active ingredients in each group, such as ginsenosides and icariin, was determined by HPLC.

[0061] The extraction efficiency was determined and the content of active ingredients per gram of medicinal material was compared.

[0062] Evaluation Metrics: Extraction efficiency: the extraction rate of the active ingredients of medicinal materials (comparison of the concentration changes of the active ingredients before and after the experiment).

[0063] Extraction rate: the amount of active ingredient released at different time points during the extraction process.

[0064] Ingredient stability: Are there any ingredients that break down or are lost during the extraction process?

[0065] Experiment 2: Comparison of drug stability and ingredient retention Experimental objectives: The effects of auxiliary materials such as β-cyclodextrin and hydroxypropyl methylcellulose in the formulation of the present invention were verified, and their effects on the stability of the drug components were tested.

[0066] Experimental steps: Drug loading preparation: According to the recipe of the experimental group, a mixture of β-cyclodextrin and hydroxypropyl methylcellulose was first prepared.

[0067] The control group did not use any excipients, and only used chitosan microspheres as carriers for drug loading.

[0068] Loading process: In the example group, the inclusion complex was mixed with the ZIF-8 carrier, the pH was adjusted to 6.0, and the loading treatment was performed for 24 hours.

[0069] The control group was directly embedded with chitosan.

[0070] Stability test: The samples of different groups were subjected to accelerated stability test at 40℃ and 75% relative humidity.

[0071] Samples were taken every month to analyze the stability of its active ingredients, and HPLC was used to analyze the retention rate of the active ingredients in the samples.

[0072] Evaluation Metrics: Stability: the residual rate of the active ingredients of the drug.

[0073] Encapsulation efficiency: the efficiency of drug binding to carrier.

[0074] Ingredient release: The release characteristics of ingredients in the drug delivery system after long-term storage.

[0075] Experiment 3: Drug sustained release effect and dissolution test Experimental objectives: The improvement effects of the gradient drying technology and nano-drug loading technology in Example 3 on drug sustained release time and drug release amount were verified.

[0076] Experimental steps: Preparation of drug delivery system: The drug delivery system was prepared using the formulation of the present invention, using a ZIF-8 carrier, and after loading the drug, a gradient drying process (humidity 60%→45°C, humidity 30%→60°C, humidity 15%→70°C) was used, with a total of 3 stages.

[0077] The control group was subjected to a single drying treatment at a constant temperature of 70°C for 4 hours.

[0078] In vitro dissolution test: The drug preparation was placed in simulated gastrointestinal fluid with pH values ​​of 1.2 (gastric fluid) and 6.8 (intestinal fluid), and the drug release was evaluated by measuring the dissolution amount.

[0079] Dissolution testing was performed by HPLC method with regular sampling to calculate the drug release rate.

[0080] Evaluation Metrics: Initial release rate: the initial rate of drug release (the amount of drug released per unit time).

[0081] Total release: The total amount of drug released within 24 hours.

[0082] Sustained release time: the time over which a drug is released stably.

[0083] Experiment 4: Bioavailability comparison experiment Experimental objectives: Verify whether the overall technical solution of the present invention significantly improves the bioavailability of the drug, especially in terms of improving drug absorption and biological half-life.

[0084] Experimental steps: Sample preparation: After in vitro dissolution testing, each group of drugs was made into oral tablets to ensure consistent drug dosage.

[0085] In vivo pharmacokinetic testing: Different groups of oral tablets were orally administered to rats as experimental subjects, and blood samples were collected regularly.

[0086] LC-MS / MS technology was used to determine blood drug concentrations, calculate parameters such as Cmax, Tmax, and AUC, and then estimate bioavailability.

[0087] Evaluation Metrics: Bioavailability (F): The bioavailability of the drug was calculated based on the comparison of AUC and Cmax with the control group.

[0088] Cmax, Tmax: maximum blood drug concentration and time to reach maximum concentration.

[0089] Experimental data: Table 1: Extraction efficiency comparison data Table 2: Comparative data of drug sustained release effect Table 3: Bioavailability comparison data This experiment fully verified the innovation and comprehensive advantages of the formula and process of the present invention. 2 The combination of extraction and decocting greatly improves the extraction efficiency of the effective ingredients of the medicinal materials, which is nearly 40% higher than the traditional decoction method. In particular, the formula design of the present invention, especially the synergistic effect of key ingredients such as ginseng, deer antler, and epimedium, makes the drug effect more significant.

[0090] In terms of drug stability, the addition of excipients β-cyclodextrin and hydroxypropyl methylcellulose, combined with nano-drug delivery technology, effectively ensures the stability of the ingredients, and optimizes the sustained-release effect of the drug through gradient drying technology. Compared with traditional processes, the sustained-release time is extended by more than three times, ensuring that the drug exerts its therapeutic effect in the body for a long time.

[0091] The improvement in bioavailability of the present invention, especially in indicators such as AUC and Cmax, shows that after adopting the formulation and process of the present invention, the absorption rate and bioavailability of the drug are significantly improved, reflecting the superiority of the overall technical solution.

[0092] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A Chinese medicine formula for treating male impotence and premature ejaculation, characterized in that: The invention comprises the following ingredients in parts by weight: 5-30 parts of ginseng, 3-25 parts of pilose antler, 2-15 parts of deer whip, 3-20 parts of processed Morinda officinalis, 4-25 parts of epimedium, 2-18 parts of Cistanche deserticola, 1-10 parts of bone marrow tonic, 2-12 parts of stir-fried Euryale ferox, 3-18 parts of wolfberry, 1-8 parts of lotus seeds, 0.5-5 parts of lotus stamens, 2-15 parts of eucommia ulmoides charcoal, 0.5-6 parts of star anise, 0.3-4 parts of fennel, 1-9 parts of leek seeds, 2-15 parts of poria, 1-10 parts of oriental water plantain, 0.1-3 parts of isatis salt, 1-12 parts of phellodendron, 0.5-8 parts of Achyranthes bidentata, 1-8 parts of schizonepeta tenuifolia, and 0.5-5 parts of herba rejuvenati.

2. A Chinese medicine formula for treating male impotence and premature ejaculation according to claim 1, characterized in that: The mass ratio of ginseng, pilose antler and epimedium is 1:0.3-0.7:0.4-0.9, and the bone marrow supplement accounts for 8-15% of the mass of Eucommia ulmoides charcoal.

3. A Chinese medicine formula for treating male impotence and premature ejaculation according to claim 1, characterized in that: It also includes 0.5-4 parts of beta-cyclodextrin and 1-6 parts of hydroxypropyl methylcellulose, and the mass ratio of beta-cyclodextrin to total flavonoids is 1:3-1:

8.

4. A method for preparing a Chinese medicine formula for treating male impotence and premature ejaculation according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1. Wall breaking and activation: freeze the antlers and penises with liquid nitrogen to -60--80°C and break them into 0.5-2 mm particles; S2, step extraction: Ginseng and epimedium are first extracted with supercritical CO2, and then refluxed with 50-70% ethanol; S3, low temperature enzymatic hydrolysis: react the S1 treated material with protease at 35-55°C for 1.5-4 h, with the added amount of protease being 1200-2500 U / g; S4, nano-reconstruction: the extracts of Phellodendron amurense and Poria cocos were encapsulated with ZIF-8 carrier at pH 5.6-6.4; S5, gradient drying: adjust the humidity in stages from 60% to 15%, and increase the temperature from 45℃ to 70℃.

5. A method for preparing a traditional Chinese medicine formula for treating male impotence and premature ejaculation according to claim 4, characterized in that: The pressure of supercritical CO2 extraction in step S2 is 28-35 MPa, the entrainer is a mixture of ethyl acetate and acetone, the volume ratio of the two is 1:2-1:4, and the total addition amount is 9-13%.

6. A method for preparing a traditional Chinese medicine formula for treating male impotence and premature ejaculation according to claim 4, characterized in that: The protease in step S3 is a composite enzyme system composed of trypsin and flavor protease at an activity ratio of 3:1-5:1, and 20-40 kHz ultrasonic treatment is applied synchronously during enzymatic hydrolysis.

7. A method for preparing a traditional Chinese medicine formula for treating male impotence and premature ejaculation according to claim 4, characterized in that: The synthesis conditions of the ZIF-8 carrier in step S4 are: The zinc nitrate concentration is 0.18-0.28 mol / L, the 2-methylimidazole concentration is 0.25-0.45 mol / L, the crystallization temperature is 80-120°C, and the drug loading time is 12-24 h.

8. A method for preparing a traditional Chinese medicine formula for treating male impotence and premature ejaculation according to claim 7, characterized in that: The ZIF-8 carrier has an embedding efficiency of 65-85%, an average pore size of 0.8-1.5 nm, and a BET specific surface area of ​​≥300 m 2 / g; the XRD spectrum of the ZIF-8 carrier has characteristic diffraction peaks at 2θ of 7.3±0.2°, 12.7±0.3°, and 18.1±0.3°.

9. The method for preparing a traditional Chinese medicine formula for treating male impotence and premature ejaculation according to claim 4, characterized in that: The parameters of the staged drying in step S5 are: In the first stage, the humidity is 60±5% and the temperature is 45±2℃ for 30-60 min; The second stage is maintained at 30±5% humidity and 60±3℃ for 40-90 min; In the third stage, the humidity is 15±3% and the temperature is 70±2℃, maintained for 20-50 min.

10. A Chinese medicine composition prepared by any one of the methods of claims 4 to 9, characterized in that: The composition contains icariin ≥2.8 mg / g, ginsenoside Rg1+Rb1 ≥3.5 mg / g, berberine ≥1.2 mg / g, and echinacoside ≥0.8 mg / g.

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