A kidney-tonifying and essence-conserving preparation, a preparation method thereof and use thereof

Abstract

The application discloses a kidney-tonifying and essence-consolidating preparation as well as a preparation method and application thereof, and belongs to the technical field of medical preparations. The preparation is prepared from multiple Chinese medicinal materials such as ginseng, sea horse, psoralea, prepared rehmannia, mulberry fruit, astragalus and medlar, and follows the prescription idea of combination of tonifying qi, nourishing yin, warming kidney and consolidating essence, and is used for improving related uncomfortable symptoms caused by kidney deficiency and essence deficiency. In the preparation, step-by-step extraction, medicine taking of superfine powder, tabletting and functional coating treatment are carried out. The coating liquid is prepared by compounding alcohol-soluble coating film-forming materials and ester coating plasticizers, the plasticizers are preferably a combination of triethyl citrate and cetyl palmitate, and the coating liquid is prepared by a melting premixing and hot-solvent shearing process to form a dense and continuous composite film layer. Compared with the prior art, the application significantly reduces tablet hygroscopicity and improves friability, and has good moisture-proof performance and mechanical strength. The preparation process is reasonable, the quality is stable, the preparation is suitable for industrial production, and has a good application prospect.

Description

Technical Field

[0001] This invention relates to the field of medical preparations technology, and in particular to a kidney-tonifying and sperm-strengthening preparation, its preparation method, and its uses. Background Technology

[0002] With the accelerating pace of modern life and changes in environment and diet, chronic diseases and sub-health conditions caused by imbalances in Qi and blood and decline in organ function are on the rise, with symptoms such as kidney deficiency and essence depletion, spleen dysfunction, and insufficient Qi and blood being particularly common. Traditional Chinese medicine (TCM) has unique advantages in regulating bodily functions and improving constitution. Existing technologies have disclosed various preparations based on TCM compound formulas for improving diseases or functional disorders of the liver, kidneys, spleen, and other organs, and these are being industrialized through modern formulations such as tablets and pills.

[0003] In the existing technology, the patent with publication number CN103656468A mainly targets the pathological characteristics of fatty liver disease, focusing on soothing the liver and regulating qi, resolving phlegm and removing blood stasis, and clearing dampness and turbidity. Its indications are mainly for liver stagnation and phlegm stasis type diseases, and it is not targeted enough for functional problems with kidney deficiency and essence depletion as the core pathogenesis. Although the ginseng and deer antler essence-enhancing tablets with publication number CN105748902A have the effect of nourishing essence and blood and enhancing physical constitution, its formulation is biased towards tonification, and the improvement of formulation stability and moisture-proof performance during long-term use is still relatively limited. The traditional Chinese medicine composition with publication number CN119033851A is mainly used for Shaoyin and Taiyin combined diseases and diabetic nephropathy-related diseases. Its formula contains insects and blood-activating and collateral-dredging drugs, and the applicable population and safety range are relatively limited. It is not suitable for kidney-tonifying and essence-strengthening preparations for daily conditioning and long-term use.

[0004] Patent CN101164586B discloses a pharmaceutical composition for treating erectile dysfunction. The formula primarily consists of warming and tonifying herbs such as Cistanche deserticola, Epimedium, deer antler, Cynomorium songaricum, Aconitum carmichaelii, and cinnamon, focusing on tonifying kidney yang and promoting blood circulation. Its indications include kidney yang deficiency syndromes such as erectile dysfunction and premature ejaculation. However, this formula is predominantly warming and drying; long-term use may deplete yin essence, and its astringent effect on seminal emission is relatively weak.

[0005] Therefore, the following problems still exist in the existing technology: On the one hand, although some Chinese herbal compound prescriptions have certain tonifying or therapeutic effects, when targeting the common syndrome of kidney deficiency and essence depletion, the prescriptions are not targeted and systematic enough. Existing kidney-tonifying yang prescriptions are mostly warm and dry, lacking the overall conditioning framework of "tonifying qi, nourishing yin, warming the kidney, consolidating and astringing, and strengthening the spleen"; On the other hand, existing Chinese herbal tablets still have problems at the formulation level, such as easy moisture absorption, poor stability, and large quality fluctuations during long-term storage or use. Specifically, existing coating technologies face the following challenges: First, a single film-forming material cannot simultaneously achieve both moisture resistance and mechanical strength. While hydrophilic film-forming materials (such as pullulan and hydroxypropyl methylcellulose) have good film toughness, their moisture resistance is insufficient. Hydrophobic film-forming materials (such as shellac) have good moisture resistance, but the film layer is brittle and prone to cracking. Second, conventional coating plasticizers are mostly small molecules with strong hydrophilicity or easy migration. Although they can improve film flexibility, their effect on moisture resistance is limited. Moreover, they are prone to migration and volatilization during storage, leading to a gradual decline in film performance. Third, while directly adding hydrophobic solid excipients to the coating system can help improve moisture resistance, they are prone to agglomeration and crystallization under conventional physical suspension conditions, causing structural defects such as micropores and pitting in the film layer, which weakens the moisture resistance and mechanical strength of the film layer. Based on the above situation, there is an urgent need to provide a traditional Chinese medicine preparation that is more in line with the needs of tonifying the kidney and consolidating essence in terms of formulation mechanism, and has been effectively improved in terms of preparation process and formulation stability, so as to solve the shortcomings of the existing technology. Summary of the Invention

[0006] In view of the shortcomings of the prior art, the present invention aims to provide a kidney-tonifying and sperm-strengthening preparation, its preparation method and uses.

[0007] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0008] A method for preparing a kidney-tonifying and sperm-strengthening preparation includes the following steps:

[0009] Step 1: Take ginseng and add it to an ethanol-water solution for reflux extraction. Collect the extract and concentrate it to obtain ginseng extract. Separately, take seahorse and psoralea corylifolia, pulverize them into a very fine powder for later use.

[0010] Step 2: Take mulberry, prepared rehmannia root, astragalus root, achyranthes root, poria cocos, schisandra fruit, rosehip, stir-fried yam, polygonatum rhizome, stir-fried malt, and wolfberry fruit. Mix and grind them together, then combine them with the ginseng residue from Step 1. Add water and decoct to extract the extract. Filter and combine the decoctions, then concentrate under reduced pressure to obtain concentrated extract.

[0011] Step 3: Mix the concentrated extract obtained in Step 2 with the ginseng extract, seahorse and psoralea corylifolia powder prepared in Step 1, add filler, pulverize into fine powder, make soft material, granulate, dry, add lubricant and press into tablets; spray the tablets with coating liquid for coating and curing, and the product is obtained.

[0012] The coating solution is prepared by mixing 30-45 parts of coating film-forming material, 8-12 parts of coating plasticizer, and 18-22 parts of talc powder with 500-700 parts of 70%-80% ethanol aqueous solution, by weight.

[0013] The coating film-forming material is hydroxypropyl methylcellulose succinate; the coating plasticizer is a compound of triethyl citrate and cetyl palmitate in a mass ratio of 0.5-2:0.5-2.

[0014] The active pharmaceutical ingredient comprises, by weight, the following:

[0015] Ginseng 110-130 parts, seahorse 20-30 parts, psoralea corylifolia 100-120 parts, mulberry 100-120 parts, prepared rehmannia root 100-120 parts, astragalus membranaceus 200-240 parts, achyranthes bidentata 100-120 parts, poria cocos 110-130 parts, schisandra chinensis 100-120 parts, rosa laevigata 100-120 parts, stir-fried yam 150-170 parts, polygonatum sibiricum 150-170 parts, stir-fried malt 150-170 parts, and wolfberry 150-170 parts.

[0016] In step 1, the reflux extraction conditions for ginseng are as follows: add an aqueous ethanol solution with a concentration of 60%-80%, extract 2-4 times at a temperature of 75℃-85℃, and each extraction takes 30-60 minutes; the seahorse and psoralea corylifolia are pulverized and passed through a 100-140 mesh sieve.

[0017] In step 2, the mixed medicinal materials are pulverized into 6-10 mesh particles; the amount of water added is 8-12 times the weight of the medicinal materials, and the decoction is carried out 2-4 times, each time for 1-2 hours; the control parameters for the concentrated extract are: the relative density measured at 60℃ at the concentration temperature is 1.15-1.25.

[0018] In step 3, the amount of filler added is 20%-30% of the total mass; the filler is composed of pharmaceutical dextrin, microcrystalline cellulose, and sodium carboxymethyl starch in a mass ratio of 0.8-1.2:0.6-1.0:0.1-0.3.

[0019] In step 3, the soft material is made using 10%-15% by weight of 80%-90% sucrose syrup as a binder; granulation is performed through a 12-18 mesh sieve; the drying temperature is 55℃-65℃, and the material is dried to a moisture content of 3.0%-5.0%; the lubricant is magnesium stearate, and the amount added is 0.5%-1.0% of the total mass.

[0020] In step 3, the control parameters for the coating process are as follows: preheating bed temperature 38℃-45℃, inlet air temperature 60℃-70℃, outlet air temperature 40℃-50℃, spray pressure 0.30MPa-0.40MPa, and pot rotation speed 15rpm-22rpm; the coating weight gain is controlled at 2%-4% of the original film weight; the curing conditions are a rotation speed of 3-8rpm and hot air curing for 15-25 minutes.

[0021] Preferably, the coating solution is prepared as follows, by weight: triethyl citrate and cetyl palmitate are first melt-mixed at 50℃-60℃ to form a homogeneous liquid mixed ester, then added to 100-300 parts of a 70%-80% ethanol aqueous solution at 65℃-75℃ and sheared and dispersed for 3-5 minutes. Then, the dispersed mixed ester solution, 30-45 parts of coating film-forming material, and 18-22 parts of talc are added to 300-500 parts of a 70%-80% ethanol aqueous solution at 65℃-75℃ and mixed to prepare the coating solution. The temperature of the coating solution is maintained at 40℃-45℃ during the coating process.

[0022] The aforementioned kidney-tonifying and sperm-strengthening preparation is used in the preparation of medicines for treating symptoms of kidney deficiency and sperm depletion, soreness and weakness of the lower back and knees, and fatigue.

[0023] The following is a description of the efficacy and compatibility mechanism of each medicinal material in the formulation of this invention:

[0024] Ginseng: It greatly replenishes vital energy, restores pulse and consolidates the body, strengthens the spleen and lungs, promotes body fluid production and calms the mind. It is used for qi deficiency and fatigue, spleen and lung weakness, etc.

[0025] Seahorse: It warms the kidneys and strengthens yang, disperses nodules and reduces swelling. It is used for impotence, infertility, and soreness of the waist and knees caused by insufficient kidney yang.

[0026] Psoralea corylifolia: It tonifies the kidneys and strengthens yang, consolidates essence and reduces urination, warms the spleen and stops diarrhea. It is used for kidney deficiency with seminal emission, frequent urination and diarrhea due to spleen and kidney yang deficiency.

[0027] Mulberry: Nourishes yin and blood, generates fluids and moistens dryness. It is used for dizziness, tinnitus, thirst and other symptoms caused by insufficient yin and blood in the liver and kidneys.

[0028] Rehmannia glutinosa (processed): Nourishes blood and yin, replenishes essence and marrow, and is used for symptoms such as soreness and weakness of the waist and knees, dizziness and tinnitus caused by deficiency of liver and kidney yin and insufficient essence and blood.

[0029] Astragalus: It tonifies Qi and raises Yang, strengthens Wei Qi and consolidates the exterior, promotes diuresis and reduces swelling, and promotes tissue regeneration and detoxification. It is used for Qi deficiency and fatigue, spontaneous sweating, and weakness due to prolonged illness.

[0030] Achyranthes bidentata: It nourishes the liver and kidneys, strengthens tendons and bones, invigorates blood circulation and promotes menstruation, and guides blood downwards. It is used for lower back and knee pain and related symptoms caused by blood stasis.

[0031] Poria cocos: It promotes diuresis and eliminates dampness, strengthens the spleen, and calms the mind. It is used for spleen deficiency with dampness, fatigue, poor appetite, palpitations, and insomnia.

[0032] Schisandra chinensis: It has astringent and consolidating properties, replenishes qi and promotes the production of body fluids, tonifies the kidneys and calms the mind. It is used for chronic cough and wheezing, spontaneous sweating and night sweats, and seminal emission and spermatorrhea.

[0033] Rosehip: It strengthens the kidneys and reduces urination, astringes and stops diarrhea. It is used for seminal emission, frequent urination, and chronic diarrhea caused by kidney deficiency.

[0034] Stir-fried yam: It nourishes the spleen and stomach, promotes the production of body fluids and benefits the lungs, and tonifies the kidneys and astringes essence (stir-frying tends to strengthen the spleen, stop diarrhea, and astringe). It is used for chronic diarrhea due to spleen deficiency and seminal emission due to kidney deficiency.

[0035] Polygonatum: It replenishes qi and nourishes yin, strengthens the spleen, moistens the lungs, and benefits the kidneys. It is used for spleen and stomach weakness, yin deficiency and fluid depletion, and kidney deficiency and fatigue.

[0036] Roasted malt: It promotes digestion, strengthens the spleen and stomach, reduces lactation and relieves bloating (roasting helps with digestion and harmonizes the stomach), and is used for indigestion, abdominal distension, etc.

[0037] Goji berries: Nourish the liver and kidneys, benefit essence and improve eyesight. Used for symptoms such as soreness and weakness of the lower back and knees, dizziness and blurred vision caused by liver and kidney yin deficiency.

[0038] This invention takes kidney deficiency and essence depletion as its core pathogenesis and establishes a holistic conditioning framework that combines five methods: "tonifying qi and consolidating the foundation, nourishing yin and replenishing essence, warming the kidneys and assisting yang, consolidating the essence gate, and strengthening the spleen and promoting its function." Specifically: Ginseng and Astragalus are used as the chief herbs, focusing on tonifying the original qi and raising yang to consolidate the exterior, thus strengthening the source of kidney essence from the level of "qi"; Rehmannia glutinosa, mulberry, and wolfberry are used as the assistant herbs, which together focus on nourishing the yin of the liver and kidneys and replenishing essence and marrow. Among them, mulberry has both yin-nourishing and astringent effects, forming a synergistic mechanism of "yin-nourishing and astringent" with wolfberry and Rehmannia glutinosa; Seahorse and Psoralea corylifolia are used as adjuvant herbs to warm the kidneys and assist yang, seeking yang within yin, so that yang generates yin. This formula is characterized by its core astringent pair of Schisandra chinensis and Rosa laevigata. Schisandra chinensis astringes and consolidates, replenishes qi and generates fluids, while Rosa laevigata consolidates essence, reduces urination, and astringes the intestines to stop diarrhea. The two work synergistically to directly target the critical pathogenesis of "weak seminal control." It is further enhanced by stir-fried Dioscorea opposita, Polygonatum sibiricum, and stir-fried malt, which invigorate the spleen, replenish qi, and promote the transformation and elimination of dampness. This embodies the holistic TCM view of "nurturing the innate through the acquired," preventing tonifying drugs from hindering the stomach and spleen, and strengthening the spleen and stomach to enhance the generation and retention of kidney essence. The entire formula achieves the overall therapeutic goal of tonifying the kidneys and consolidating essence, addressing both the root cause and the symptoms, through the synergistic effects of tonifying, nourishing, warming, astringing, and promoting circulation.

[0039] In view of the different physicochemical properties of saponins and other water-soluble components in ginseng, an extraction method combining alcohol extraction and water decoction was designed, and ultra-fine powder was added directly to the medicine to maximize the retention and synergistic effect of various effective components, thereby improving the overall bioavailability and efficacy stability.

[0040] In response to the problems of easy moisture absorption and poor stability of traditional Chinese medicine compound tablets, this invention introduces a specific polymer coating system. By controlling the coating weight gain and curing conditions, a stable moisture barrier is formed, which reduces the impact of environmental humidity on the active ingredients, ensures the release performance of the tablets, and achieves long-term stable efficacy of the formulation.

[0041] This invention first recognizes that the moisture absorption of tablets mainly originates from the diffusion and penetration of water vapor in the coating film. Therefore, the coating system selects film-forming materials that are soluble in ethanol-water systems and can form a dense and continuous film layer after curing, including cellulose derivatives with ester substituents and natural proteins rich in hydrophobic amino acids. By utilizing the continuous and dense structure formed on the tablet core surface after film formation, the channels for water vapor to permeate are reduced at the molecular level, thereby achieving the basic moisture-proof function of the coating film.

[0042] To address the contradiction that insufficient plasticization of a single film-forming material leads to film brittleness, while simple plasticization is insufficient for moisture barrier properties, this invention combines liquid small-molecule ester plasticizers with solid long-chain wax esters. The liquid small-molecule esters insert between polymer molecular chains, weakening interchain forces and making the film flexible and dense. The solid long-chain wax esters, with their strong hydrophobicity, embed and occupy the free volume between polymer chains, extending the water vapor diffusion path and reducing the water vapor permeation rate. The ester group structures of the two are compatible. The liquid plasticizer can inhibit film embrittlement caused by wax ester crystallization, while the solid wax ester can anchor the liquid plasticizer, reducing its migration and volatilization losses. This forms a structure in which liquid plasticization and solid moisture barrier work together and are mutually stable, achieving a synergistic improvement in moisture resistance and anti-brittleness at the structural level.

[0043] To avoid agglomeration and micropore defects caused by direct physical suspension of solid wax esters, this invention further employs a dispersion process combining melt premixing and thermal shearing: first, liquid ester plasticizers and solid wax esters are melt-mixed at a temperature above the melting point of the wax esters to form a homogeneous liquid mixed ester; then, this mixture is dispersed in a hot ethanol-water solution under high-speed shearing, causing the wax esters to be uniformly dispersed in the coating solution in a fine state. During the coating process, the temperature of the coating solution is maintained, promoting the formation of a dense, continuous composite network structure between the wax esters and the polymer, thereby maximizing moisture barrier efficiency and enhancing the mechanical bonding of the film layer. Compared to conventional physical suspension processes, this process eliminates micropores and structural defects in the film layer caused by wax ester agglomeration and crystallization, forming a dense, homogeneous, and continuous hydrophobic barrier.

[0044] The coating plasticizer is at least one of triethyl citrate, glyceryl acetate, and cetyl palmitate.

[0045] The coating film-forming material is at least one of hydroxypropyl methylcellulose acetate succinate, zein, and carboxymethyl ethyl cellulose.

[0046] Compared with the prior art, the present invention has the following beneficial technical effects:

[0047] 1) This invention targets the core pathogenesis of kidney deficiency and essence depletion, and constructs an overall conditioning framework that combines five methods: tonifying qi, nourishing yin, warming the kidney, consolidating and astringing, and strengthening the spleen. The combination of each herb in the formula conforms to the theory of traditional Chinese medicine, treating both the symptoms and the root cause, and avoiding the shortcomings of existing kidney-tonifying yang formulas that tend to be warm and dry.

[0048] 2) This invention employs a process that combines stepwise extraction with the use of ultrafine powder in medicine, which significantly improves the retention rate and utilization of effective ingredients, reduces ingredient loss, and ensures consistency of efficacy between batches.

[0049] 3) This invention utilizes a functional coating technology that combines liquid ester plasticizers with solid wax esters, supplemented by melt premixing and hot melt shearing processes, to significantly reduce the hygroscopicity of tablets, improve brittleness, enhance formulation stability and storage safety, and overcome the technical defects of existing Chinese medicine tablets that are prone to moisture absorption and deterioration. Detailed Implementation

[0050] Ginseng, a commercially available product, originating from Changbai Mountain, Jilin Province.

[0051] Seahorse, a commercially available product, originating from Luoyuan County, Fujian Province.

[0052] Psoralea corylifolia, a commercially available product, originating from Baoding, Hebei Province.

[0053] Mulberries, a commercially available product, originating from Dechang, Sichuan.

[0054] Rehmannia glutinosa (processed), a commercially available product, originating from Jiaozuo, Henan.

[0055] Astragalus membranaceus, a commercially available product, originating from Minxian County, Gansu Province.

[0056] Achyranthes bidentata, a commercially available product, originating from Jiaozuo, Henan.

[0057] Poria cocos, a commercially available product, originating from Jingzhou, Hunan.

[0058] Schisandra chinensis, a commercially available product, originating from Changbai Mountain, Jilin Province.

[0059] Golden cherry fruit, a commercially available product, originating from De'an County, Jiangxi Province.

[0060] Stir-fried yam, a commercially available product, originating from Jiaozuo, Henan.

[0061] Polygonatum sibiricum, a commercially available product, originating from Qingyang County, Anhui Province.

[0062] Roasted malt, a commercially available product, originating from Yanjin County, Henan Province.

[0063] Goji berries, a commercially available product, originating from Zhongning County, Ningxia Hui Autonomous Region.

[0064] Pharmaceutical grade dextrin, pharmaceutical grade, conforming to Chinese Pharmacopoeia (ChP) standards, DE value (glucose equivalent): not less than 10%, loss on drying: ≤10.0%.

[0065] Microcrystalline cellulose, pharmaceutical grade, particle size: approximately 50 μm, bulk density: 0.26-0.31 g / cc.

[0066] Sodium carboxymethyl starch, pharmaceutical grade disintegrant, pH: 5.5-7.5, sodium content: 2.8%-4.2%.

[0067] Sucrose syrup, pharmaceutical grade, specific rotation: +66.3° to +67.0°, purity: ≥99.5%.

[0068] Magnesium stearate, medicinal plant-derived grade, magnesium content (as MgO): 4.0%-5.0%, fineness: passing through a 200-mesh sieve, specific surface area: 6-12 m² 2 / g.

[0069] Hydroxypropyl methylcellulose acetate succinate, pharmaceutical excipient grade, average particle size: 5-10μm, succinyl group content: 10.0%-14.0%, acetyl group content: 7.0%-11.0%.

[0070] Talc powder, pharmaceutical grade, fineness: 325 mesh.

[0071] Zea protein, pharmaceutical excipient grade, protein content (on a dry basis): ≥90.0%, solubility: soluble in 70%-80% ethanol aqueous solution.

[0072] Carboxymethyl ethyl cellulose, pharmaceutical grade, ethanol insoluble matter: ≤1.5%.

[0073] In the embodiments and comparative examples of this invention, all raw materials are commercially available products.

[0074] Example 1

[0075] The preparation method of a kidney-tonifying and sperm-strengthening preparation is as follows, in parts by weight:

[0076] Step 1: Take 120 parts of ginseng, add 70% ethanol aqueous solution and reflux extract three times at 80℃, each extraction time is 45 minutes, collect the extract and filter, combine the filtrates and recover the ethanol, concentrate to the paste for later use; take 25 parts of seahorse and 110 parts of psoralea, crush them to pass through a 120 mesh sieve to obtain a very fine powder, seal for later use.

[0077] Step 2: Weigh out 110 parts of mulberry, 110 parts of prepared rehmannia root, 220 parts of astragalus root, 110 parts of achyranthes root, 120 parts of poria cocos, 110 parts of schisandra fruit, 110 parts of rosehip, 160 parts of stir-fried yam, 160 parts of polygonatum rhizome, 160 parts of stir-fried malt, and 160 parts of wolfberry fruit. Mix the above medicinal materials and pulverize them into 8-mesh particles. Combine them with the ginseng residue extracted in Step 1. Add water equal to 10 times the weight of the medicinal materials to the mixture, heat and decoct 3 times, each time for 1.5 hours. Filter the decoction and combine them. Use a vacuum concentration process to control the concentration temperature, so that the filtrate is concentrated to a concentration of 1.18 at 60°C.

[0078] Step 3: Add the ginseng extract and seahorse and psoralea corylifolia powder prepared in Step 1 to the concentrated extract obtained in Step 2, and add 25% of the total mass of filler, and stir thoroughly. The filler is prepared by mixing pharmaceutical dextrin, microcrystalline cellulose, and sodium carboxymethyl starch in a mass ratio of 1:0.8:0.2. After the mixture is dried at low temperature, it is pulverized into a fine powder. Using 12% of the total mass of 85% sucrose syrup as a binder, a soft mass is prepared and granulated through a 15-mesh sieve. The wet granules are then dried in a ventilated environment at 60°C. The moisture content was reduced to 4.0%. Finally, 0.8% magnesium stearate was added as a lubricant. After mixing evenly, the mixture was compressed into tablets weighing 0.35 parts each. The tablets were placed in a high-efficiency coating pan, and the tablet bed temperature was preheated to 42°C. The coating liquid was sprayed, and the following parameters were controlled: inlet air temperature 65°C; outlet air temperature 45°C; spray pressure 0.35MPa; pan rotation speed 18rpm; the coating weight gain was controlled at 3% of the weight of the tablets. After coating, the pan was rotated at 5rpm and hot air was circulated for 20 minutes to cure, thus obtaining the kidney-tonifying and sperm-strengthening preparation.

[0079] The coating solution is prepared by mixing 45 parts of coating film-forming material, 10 parts of coating plasticizer, and 20 parts of talc powder with 600 parts of 75% ethanol aqueous solution.

[0080] The coating film-forming material is hydroxypropyl methylcellulose acetate succinate; the coating plasticizer is triethyl citrate.

[0081] Example 2

[0082] The preparation method of a kidney-tonifying and sperm-strengthening preparation is basically the same as that in Example 1, except that the coating film-forming material in the coating solution is zein; and the coating plasticizer is triethyl citrate.

[0083] Example 3

[0084] The preparation method of a kidney-tonifying and sperm-strengthening preparation is basically the same as that in Example 1, except that the coating film-forming material in the coating solution is carboxymethyl ethyl cellulose and the coating plasticizer is triethyl citrate.

[0085] Example 4

[0086] The preparation method of a kidney-tonifying and sperm-strengthening preparation is basically the same as that in Example 1, except that the coating film-forming material in the coating solution is hydroxypropyl methylcellulose succinate; and the coating plasticizer is glyceryl acetate.

[0087] Example 5

[0088] The preparation method of a kidney-tonifying and sperm-strengthening preparation is basically the same as that in Example 1, except that the coating film-forming material in the coating solution is hydroxypropyl methylcellulose acetate succinate; and the coating plasticizer is cetyl palmitate.

[0089] Example 6

[0090] The preparation method of a kidney-tonifying and sperm-strengthening preparation is basically the same as that in Example 1, except that: the coating film-forming material in the coating solution is hydroxypropyl methylcellulose acetate succinate; the coating plasticizer is composed of triethyl citrate and cetyl palmitate in a mass ratio of 1:1.

[0091] Example 7

[0092] The preparation method of a kidney-tonifying and sperm-strengthening preparation is basically the same as that in Example 1, except that the coating film-forming material in the coating solution is hydroxypropyl methylcellulose succinate; and the coating plasticizer is composed of triethyl citrate and glyceryl acetate in a mass ratio of 1:1.

[0093] Example 8

[0094] The preparation method of a kidney-tonifying and sperm-strengthening preparation is basically the same as that in Example 6, except that: 5 parts of cetyl palmitate and 5 parts of triethyl citrate are first melted and mixed in a water bath at 55°C to form a homogeneous liquid ester mixture, and then added to 150 parts of 75% ethanol aqueous solution at 70°C for shearing and dispersion for 4 minutes. Then, the dispersed solution, 45 parts of coating film-forming material, and 20 parts of talc are added to 450 parts of 75% ethanol aqueous solution at 70°C and mixed to prepare the preparation.

[0095] Comparative Example 1

[0096] The preparation method of a kidney-tonifying and sperm-strengthening preparation is basically the same as that in Example 1, except that no coating is performed.

[0097] Test Example 1

[0098] Moisture resistance test

[0099] Sixty tablets were taken from each of the kidney-tonifying and sperm-strengthening preparations obtained in the examples and comparative examples, selecting tablets that were intact and undamaged. The experiment used bare tablets (without any outer packaging) to demonstrate the differences in moisture-barrier properties of the coating. The experimental conditions were a constant temperature and humidity chamber: 40℃±2℃, 75%±5%RH. Tablets from each group were laid flat in a single layer on a clean tray, avoiding mutual obstruction; each group was labeled separately and left for 14 days.

[0100] Moisture absorption weight gain determination: Before the test, 10 tablets were randomly selected from each group, and each tablet was weighed and the initial mass W0 of each tablet was recorded; after 14 days, 10 tablets from the same batch were taken out, and visible condensation on the surface was quickly wiped off (if there was no condensation, no treatment was required), and each tablet was weighed and the W0 was recorded. t .

[0101] Calculate: Moisture absorption weight gain rate (%) = (W t -W0) / W0×100%.

[0102] The test results are averaged, see Table 1.

[0103] Table 1

[0104]

[0105] Test Example 2

[0106] Tablet friability test

[0107] For each of the kidney-tonifying and sperm-strengthening preparations obtained in the examples and comparative examples, take 20 tablets, remove the powder, and record the total mass W0. Process the 20 tablets using a tablet friability tester at 50 rpm for 4 minutes. After the test, remove the tablets, remove the surface powder (lightly brush with a soft brush), and weigh the total mass to obtain W1.

[0108] Calculate the friability (%) = (W0 - W1) / W0 × 100%

[0109] Each group was measured in parallel three times, and the average value was taken. The relevant test data are summarized in Table 2.

[0110] Table 2

[0111]

[0112] It should be noted that the following description of the mechanism of action is an analysis made by the applicant based on the above experimental results, used to help understand the present invention, and does not constitute a limitation on the scope of protection; the technical effects of the present invention have been directly confirmed by the experimental data of the above test examples.

[0113] Hydroxypropyl methylcellulose acetate succinate is an alcohol-soluble enteric film-forming material. Its molecular chain contains acetyl and succinyl substituents and retains hydroxyl groups that can form hydrogen bonds, allowing it to dissolve in aqueous ethanol and form a continuous film. Triethyl citrate is a small-molecule citrate ester. Its ester group structure is similar to that of hydroxypropyl methylcellulose acetate succinate, resulting in good compatibility. When triethyl citrate enters the polymer molecular chains, it weakens the intermolecular forces, increases chain mobility, and facilitates film spreading during film formation. This results in a continuous, dense, and flexible film, reducing porosity and defects, decreasing the pathway for external moisture to enter the tablet core, and imparting good flexibility to the film, thus improving tablet brittleness.

[0114] Cetyl palmitate is a solid wax ester formed by the esterification of long-chain fatty acids and long-chain fatty alcohols. It is highly hydrophobic and, upon entering the membrane layer, occupies the free volume between polymer molecular chains, prolonging the diffusion path of water molecules within the membrane layer and thus reducing the rate of water vapor permeation. Both triethyl citrate and cetyl palmitate contain ester groups in their molecules, exhibiting good compatibility. When combined, they form a uniformly mixed ester phase. On one hand, liquid triethyl citrate disperses around cetyl palmitate, inhibiting its crystallization and preventing membrane embrittlement and surface defects caused by wax ester crystallization. On the other hand, solid cetyl palmitate anchors triethyl citrate, reducing its migration and volatilization loss during storage, thus maintaining the plasticizing effect over a long period. The two form a mutually synergistic and stable state of liquid plasticizing and solid moisture barrier within the membrane layer; therefore, the moisture-proof and anti-brittleness properties of the combined product are superior to those of either product used alone. Triethyl citrate and glyceryl acetate are both liquid small-molecule ester plasticizers with the same plasticizing mechanism. When combined, their effects are simply additive, without producing a synergistic effect. This indicates that the synergistic effect stems from the structural and functional complementarity between the liquid small-molecule ester and the solid long-chain wax ester, rather than a simple combination of any two plasticizers. Furthermore, the experimental data directly ruled out the adverse effect of wax esters increasing film rigidity. Table 2 shows that cetyl palmitate alone increases tablet friability, indicating that wax esters alone do tend to increase film rigidity. However, the combination of triethyl citrate and cetyl palmitate significantly reduces friability, proving that the liquid plasticizer in the compound system effectively inhibits the wax esters' activity and does not produce an adverse effect of increased rigidity.

[0115] Cetyl palmitate has a high melting point and poor solubility in aqueous ethanol at room temperature. It can only disperse as relatively coarse particles in the coating solution, and it easily recrystallizes and precipitates after the temperature decreases, resulting in uneven coating, uneven spraying, and pitting on the film surface. This leads to uneven distribution of the two esters in the film layer, preventing the full realization of the synergistic effect of the compound. A process combining melt premixing and hot-melt shearing is employed. Triethyl citrate and cetyl palmitate are first melt-mixed under heating to form a homogeneous liquid ester mixture. This mixture is then dispersed in a hot aqueous ethanol solution, and the temperature of the coating solution is maintained during the coating process. This ensures that the two esters remain uniformly mixed before film formation and are simultaneously and uniformly distributed within the film layer formed by hydroxypropyl methylcellulose acetate succinate during film formation, preventing crystallization and phase separation. The resulting film is denser, more uniform, and more flexible. Therefore, the process conditions of melt premixing, hot-melt shearing, and heat-preserving spraying are interdependent with this compound combination, further enhancing the synergistic effect.

Claims

1. A method for preparing a kidney-tonifying and sperm-strengthening preparation, characterized in that, Includes the following steps: Step 1: Take ginseng and add it to an ethanol-water solution for reflux extraction. Collect the extract and concentrate it to obtain ginseng extract. Separately, take seahorse and psoralea corylifolia, pulverize them into a very fine powder for later use. Step 2: Take mulberry, prepared rehmannia root, astragalus root, achyranthes root, poria cocos, schisandra fruit, rosehip, stir-fried yam, polygonatum rhizome, stir-fried malt, and wolfberry fruit. Mix and grind them together, then combine them with the ginseng residue from Step 1. Add water and decoct to extract the extract. Filter and combine the decoctions, then concentrate under reduced pressure to obtain concentrated extract. Step 3: Mix the concentrated extract obtained in Step 2 with the ginseng extract, seahorse and psoralea corylifolia powder prepared in Step 1, add filler, pulverize into fine powder, make soft material, granulate, dry, add lubricant and press into tablets; spray the tablets with coating liquid for coating and curing, and the product is obtained. The coating solution is prepared by mixing 30-45 parts of coating film-forming material, 8-12 parts of coating plasticizer, and 18-22 parts of talc powder with 500-700 parts of 70%-80% ethanol aqueous solution, by weight. The coating film-forming material is hydroxypropyl methylcellulose succinate; the coating plasticizer is a compound of triethyl citrate and cetyl palmitate in a mass ratio of 0.5-2:0.5-2.

2. The preparation method according to claim 1, characterized in that, The active pharmaceutical ingredient comprises, by weight, the following: Ginseng 110-130 parts, seahorse 20-30 parts, psoralea corylifolia 100-120 parts, mulberry 100-120 parts, prepared rehmannia root 100-120 parts, astragalus membranaceus 200-240 parts, achyranthes bidentata 100-120 parts, poria cocos 110-130 parts, schisandra chinensis 100-120 parts, rosa laevigata 100-120 parts, stir-fried yam 150-170 parts, polygonatum sibiricum 150-170 parts, stir-fried malt 150-170 parts, and wolfberry 150-170 parts.

3. The preparation method according to claim 1, characterized in that, The reflux extraction conditions for ginseng in step 1 are as follows: add an ethanol aqueous solution with a concentration of 60%-80%, extract 2-4 times at a temperature of 75℃-85℃, and each extraction time is 30-60 minutes; after crushing the seahorse and psoralea, pass them through a 100-140 mesh sieve.

4. The preparation method according to claim 1, characterized in that, In step 2, the mixed medicinal materials are pulverized into 6-10 mesh particles; the amount of water added is 8-12 times the weight of the medicinal materials, and the decoction is carried out 2-4 times, each time for 1-2 hours; the control parameters for the concentrated extract are: the relative density measured at 60℃ at the concentration temperature is 1.15-1.

25.

5. The preparation method according to claim 1, characterized in that, In step 3, the amount of filler added is 20%-30% of the total mass; the filler is composed of pharmaceutical dextrin, microcrystalline cellulose, and sodium carboxymethyl starch in a mass ratio of 0.8-1.2:0.6-1.0:0.1-0.

3.

6. The preparation method according to claim 1, characterized in that, In step 3, 10%-15% of the total mass of sucrose syrup with a concentration of 80%-90% is used as a binder for making the soft material; granulation is performed through a 12-18 mesh sieve; the drying temperature is 55℃-65℃, and the material is dried to a moisture content of 3.0%-5.0%; the lubricant is magnesium stearate, and the amount added is 0.5%-1.0% of the total mass.

7. The preparation method according to claim 1, characterized in that, The control parameters for the coating process in step 3 are as follows: preheating bed temperature 38℃-45℃, inlet air temperature 60℃-70℃, outlet air temperature 40℃-50℃, spray pressure 0.30MPa-0.40MPa, and pot rotation speed 15rpm-22rpm; the coating weight gain is controlled at 2%-4% of the original film weight; the curing conditions are a rotation speed of 3-8rpm and hot air curing for 15-25 minutes.

8. The preparation method according to claim 1, characterized in that, The coating solution can also be prepared by melting and mixing triethyl citrate and cetyl palmitate at 50℃-60℃ to form a homogeneous liquid mixed ester, and then adding it to 100-300 parts of a 70%-80% ethanol aqueous solution at 65℃-75℃ for shearing and dispersion for 3-5 minutes. Then, the dispersed mixed ester solution, 30-45 parts of coating film-forming material, and 18-22 parts of talc are added to 300-500 parts of a 70%-80% ethanol aqueous solution at 65℃-75℃ and mixed to prepare the coating solution. The temperature of the coating solution is maintained at 40℃-45℃ during the coating process.

9. A kidney-tonifying and sperm-strengthening preparation, characterized in that, It is prepared by the preparation method described in any one of claims 1-8.

10. The use of the kidney-tonifying and sperm-strengthening preparation as described in claim 9 in the preparation of a medicament for treating symptoms of kidney deficiency and sperm depletion, soreness and weakness of the lower back and knees, and fatigue.

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