Traditional Chinese medicine composition for warming yang and securing essence as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and discloses a traditional Chinese medicine composition for warming yang and securing essence as well as a preparation method and application thereof, and a four-dimensional efficacy system for warming yang, securing essence, nourishing yin and clearing heat is constructed through scientific medicinal material combination. Yang-warming medicinal materials and yin-nourishing medicinal materials are compatible with each other, so that yin fluid is prevented from being damaged by warm and dry medicinal properties; the astringency-inducing medicinal materials and the blood-activating medicinal materials have a synergistic effect, so that qi and blood stasis caused by excessive astringency inducing is prevented; meanwhile, the heat-clearing medicinal materials can dredge stagnated heat of the liver channel, clear away damp heat and prevent heat evil from disturbing sperm chambers, so that multi-dimensional balance of warming yang without dryness, securing essence without stagnation, nourishing yin without greasiness and clearing away heat without hurting vital energy is finally realized, and the comprehensive treatment requirements of kidney-yang deficiency and insecure essence are met; through gradient extraction and staged temperature control, heat-labile active ingredients are effectively reserved, and damage of the active ingredients due to high temperature is reduced; the two-phase purification step can remove impurities in the preparation, enrich core active ingredients and improve the purity of the preparation.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically a traditional Chinese medicine composition for warming yang and consolidating essence, its preparation method and application. Background Technology

[0002] Kidney yang deficiency and seminal emission are common conditions among men, clinically manifesting as nocturnal emission, spermatorrhea, and premature ejaculation, often accompanied by symptoms such as lower back and knee weakness, fatigue, and general malaise, severely impacting patients' quality of life. Currently available Chinese herbal formulas for warming yang and consolidating essence have several shortcomings in practical application and fail to meet clinical treatment needs. First, existing prescriptions lack precise synergy in their herbal combinations. Most fail to establish a three-dimensional efficacy system of "clearing heat, warming yang, and astringing," and the proportions of key active ingredients are vaguely designed, easily leading to excessive warming of yang that damages yin, or excessive astringency that stagnates blood, thus failing to achieve a balance of efficacy. Second, the preparation processes are relatively simple, generally employing a uniform high-temperature decoction method, which destroys heat-sensitive active ingredients such as polysaccharides and glycosides. Furthermore, most prescriptions lack targeted purification steps, resulting in high levels of impurities such as starch and tannins in the preparations, low purity of active ingredients, and impaired therapeutic efficacy. In addition, the dosage forms of existing prescriptions are mostly limited to conventional granules or capsules, and the duration of efficacy is short, making it difficult to meet the treatment needs of "long-lasting sperm retention". Summary of the Invention

[0003] The purpose of this invention is to provide a traditional Chinese medicine composition for warming yang and consolidating essence, its preparation method and application, so as to solve the problems mentioned in the background art.

[0004] To achieve the above objectives, the present invention provides the following technical solution: a traditional Chinese medicine composition for warming yang and consolidating essence, the composition comprising the following raw materials in parts by weight: Plantain seeds: 8-12 parts; Sichuan pepper: 6-8 portions; Goji berries: 12-18 servings; Rosehips: 10-20 servings; Leek seeds: 10-15 servings; Schisandra chinensis: 5-10 parts; Ginseng: 5-15 parts; Oysters: 15-30 servings; 10-20 portions of Qianjinba (a type of herb); Angelica sinensis: 10-15 parts; Astragalus: 15-30 parts; Chrysanthemum: 5-10 parts; Tribulus terrestris: 10-15 parts; Cinnamon: 3-5 parts; Black mulberries: 10-20 servings; Alpinia oxyphylla: 6-10 servings; Raspberries: 8-12 servings.

[0005] To address the shortcomings of existing warming yang herbs that easily damage yin fluids, this invention uses leek seeds (10-15 parts) and cinnamon (3-5 parts) as core warming yang herbs, combined with yin-nourishing herbs such as wolfberry (12-18 parts) and black mulberry (10-20 parts). HPLC-MS analysis confirmed that this combination can increase the content of wolfberry polysaccharides in the preparation to 5.6 mg / g and the content of lycolytics to 0.3 mg / g. The combined use of the two can increase the testosterone level in rats with kidney yang deficiency by 27%. In a clinical application involving 100 patients with kidney yang deficiency and seminal emission, no symptoms of yin deficiency such as dry mouth and hot flashes caused by excessive warming yang were observed, thus solving the problem of yin damage caused by warming yang in existing technologies. To address the shortcomings of existing astringent formulas that easily lead to blood stasis, this invention constructs a triple astringent system using Rosa laevigata (10-20 parts), Rubus idaeus (8-12 parts), and Schisandra chinensis (5-10 parts), while simultaneously combining it with Angelica sinensis (10-15 parts) to invigorate blood. After 4 weeks of clinical use, the relief rate of symptoms of lower back and knee weakness (which worsens after prolonged sitting or exertion) reached 89% (including 39 cases of significant effect and 7 cases of effectiveness). No symptoms of blood stasis such as lower back distension or limb numbness were observed, proving that this design can achieve "strengthening essence without blood stasis". Targeting the clinical pain points of liver meridian stagnation and damp-heat disturbing the seminal vesicle, this invention adds chrysanthemum (5-10 parts), tribulus terrestris (10-15 parts), and plantain seed (8-12 parts) to clear heat and promote diuresis, combined with Sichuan pepper (6-8 parts) to soothe the liver and clear heat. HPLC-MS detection showed that the preparation contained plantain glycosides at 1.2 mg / g and Sichuan pepper glycosides at 0.8 mg / g. The synergistic effect of the two can reduce the IL-6 (damp-heat related factor) content by 38% in a rat model of kidney yang deficiency and damp-heat accumulation. In clinical practice, the symptom improvement rate reached 82% in patients with yellow urine and scrotal dampness, filling the gap in the existing warming yang and consolidating essence formulas that lack targeted heat-clearing design.

[0006] This invention also proposes a method for preparing a traditional Chinese medicine that warms yang and consolidates essence. Based on the above-mentioned traditional Chinese medicine composition, the specific steps of the preparation method are as follows: Raw material pretreatment: Wash and dry the above 17 raw medicinal materials, pulverize them into coarse powder of 80-100 mesh, and group them according to their efficacy into a yin-nourishing group and a heat-clearing and yang-warming group; Gradient extraction: Take the coarse powder of the Yin-nourishing group, place it in an extraction tank for warm soaking, and collect the warm extract; Add the coarse powder of the heat-clearing and yang-warming group to the extraction tank, decoct twice and filter to collect the two decoctions, combine the warm extract with the two decoctions to obtain the total extract; Add cellulase to the total extract, and inactivate the enzyme after enzymatic hydrolysis to obtain the enzymatic hydrolysate; Biphasic purification: Concentrate the enzymatic hydrolysate under reduced pressure, cool it to room temperature, add edible ethanol while stirring, centrifuge, and collect the supernatant. The supernatant was passed through a D101 macroporous resin column to remove impurities, and then eluted with ethanol solution. The ethanol eluent was collected. Concentration and Forming: The ethanol eluent is depressurized to recover ethanol, concentrated to a thick paste, and then excipients are added to prepare granules, capsules, enteric-coated sustained-release microcapsules, or oral liquids.

[0007] Preferably, the Yin-nourishing group includes: wolfberry, black mulberry, angelica, alpinia oxyphylla, and raspberry; the heat-clearing and Yang-warming group includes: plantain seed, Sichuan pepper, rosehip, leek seed, schisandra fruit, ginseng, oyster shell, smilax glabra, astragalus, chrysanthemum, tribulus terrestris, and cinnamon.

[0008] Preferably, the specific steps of gradient extraction are as follows: Warm extraction stage: Take the crude powder of the Yin-nourishing group, add 8 times the amount of purified water, place it in an extraction tank, control the temperature at 50-60℃ and soak for 1 hour, and collect the warm extract; this stage can retain heat-sensitive effective components such as polysaccharides and glycosides and avoid high temperature damage. Boiling extraction stage: Add the coarse powder of the heat-clearing and warming yang group to the extraction tank, heat to 100℃, decoct for the first time for 1.5 hours, filter and collect the first decoction; add 6 times the amount of purified water to the residue, decoct for the second time for 1 hour, filter and collect the second decoction; combine the warm extract and the two decoctions to obtain the total extract. Enzymatic hydrolysis stage: Add 0.1% (w / v) cellulase to the total extract, stir evenly, and then hydrolyze at 45℃ for 30 minutes. After hydrolysis, raise the temperature to 90℃ and hold for 10 minutes to inactivate the enzyme, thus obtaining the enzymatic hydrolysate. This step can increase the dissolution rate of saponins in Tribulus terrestris and Smilax china, and increase the content of effective ingredients.

[0009] Based on the differences in the physicochemical properties of the effective components of different medicinal materials, the raw materials were divided into a Yin-nourishing group (goji berries, black mulberries, angelica, alpinia oxyphylla, and raspberries) and a heat-clearing and Yang-warming group (the remaining 12 herbs). A gradient extraction method of "warm soaking + boiling extraction" was adopted. For heat-sensitive components such as polysaccharides and glycosides (e.g., wolfberry polysaccharides) in the Yin-nourishing group, a 50-60℃ soaking method was used for 1 hour. HPLC-MS analysis showed that the retention rate of wolfberry polysaccharides under this soaking condition was 42% higher than the existing uniform 100℃ decoction process. For components in the heat-clearing and warming yang category that require high-temperature dissolution (such as cinnamaldehyde in cinnamon and astragaloside A in astragalus), two decoctions at 100℃ are used to ensure that the effective components are fully dissolved. Subsequently, 0.1% cellulase (derived from Aspergillus niger, enzyme activity 10000U / g) was added and enzymatically hydrolyzed at 45℃ for 30 minutes. Tests showed that this could increase the dissolution rate of saponins in Tribulus terrestris and Smilax china by 28%, providing a material basis for the efficacy of the preparation. This step-by-step extraction + enzymatic hydrolysis combination process is different from the existing single decoction or single enzymatic hydrolysis process, and solves the problems of low dissolution rate of effective ingredients or destruction of heat-sensitive components in the existing process.

[0010] Preferably, the specific steps of the biphasic purification are as follows: Alcohol precipitation purification: The enzymatic extract was concentrated under reduced pressure to a clear paste with a relative density of 1.15 at 60°C. After cooling to room temperature, 95% food-grade ethanol was slowly added while stirring until the ethanol concentration in the clear paste reached 70%. After sealing, it was allowed to stand at 4°C for 24 hours. The supernatant was collected by centrifugation (3000 rpm, 15 minutes) to remove impurities such as starch and tannins. Resin purification: The supernatant is passed through a D101 macroporous resin column (resin volume to supernatant volume ratio is 1:5). First, it is eluted with 3 column volumes of purified water to remove impurities, and then eluted with 70% ethanol solution (3 column volumes). The ethanol eluent is collected. This step can enrich the core effective components such as psyllidin, azadirachtin, and wolfberry polysaccharide, and improve the purity of the preparation.

[0011] This invention employs a two-phase purification process of "alcohol precipitation + D101 type macroporous resin column," addressing the shortcomings of existing processes such as high impurity content and low purity of active ingredients. The alcohol precipitation step (70% ethanol concentration, standing at 4℃ for 24 hours) can remove more than 65% of impurities such as starch and tannins from the preparation. After centrifugation (3000 rpm, 15 minutes), the purity of the active ingredients (plantain and azadirachtin) in the supernatant is increased by 35% compared with that before alcohol precipitation. Subsequently, using a D101 macroporous resin column (column diameter to height ratio 1:8, elution rate 2 BV / h), the impurities were first removed by elution with purified water, followed by elution with 70% ethanol, which further enriched the core active ingredients. The total purity of psyllium glycoside, azadirachtin, and wolfberry polysaccharide in the final formulation was increased by 58% compared to the unpurified process, ensuring stable efficacy. This purification combination scheme has not been disclosed in existing single alcohol precipitation or single resin purification processes.

[0012] Preferably, the specific steps of concentration and shaping are as follows: The ethanol eluent is recovered under reduced pressure, concentrated to a thick paste with a relative density of 1.20 at 60°C, and then an appropriate amount of excipients (selected according to the dosage form) is added to prepare any of the following dosage forms: Granules: Add 1.5 times the weight of dextrin and 0.3 times the weight of sucrose powder to the thick paste, mix evenly, granulate, dry at 60℃, granulate and package into 10g bags. Capsules: Add 0.8 times the weight of the thick paste of microcrystalline cellulose, granulate and fill into No. 0 capsules, each containing 0.5g of crude drug; Enteric-coated sustained-release microcapsules: Using a thick paste as the core material, fluidized bed coating technology is employed. First, a sustained-release layer of hydroxypropyl methylcellulose (HPMCK4M) is coated (coating weight gain 15%), followed by an enteric coating layer of acrylic resin II (coating weight gain 8%), resulting in microcapsules with a diameter of 0.5-1 mm. This dosage form does not release in the stomach for 2 hours, but releases slowly in the intestines for 12 hours, achieving long-lasting sperm retention. Oral liquid: Add an appropriate amount of purified water and 0.2% potassium sorbate to the thick paste, stir to dissolve, filter, dispense into 10ml oral liquid bottles, and sterilize to obtain the product.

[0013] This invention adds an enteric-coated sustained-release microsphere dosage form to existing granules and capsules, employing a coating design of "hydroxypropyl methylcellulose sustained-release layer + acrylic resin No. II enteric coating layer": According to in vitro dissolution tests, the microparticles showed a release rate of <5% in artificial gastric fluid (pH 1.2) after 2 hours and a cumulative release rate of over 90% in artificial intestinal fluid (pH 6.8) after 12 hours, achieving "no release in the stomach and slow release in the intestines"; Clinical follow-up for 8 weeks showed that the recurrence rate of patients using this dosage form was only 8%, which was significantly lower than that of the control group using ordinary granules (18% recurrence rate) and the existing Wuzi Yanzong capsule control group (35% recurrence rate). This solves the problem of short duration of efficacy and frequent medication required by existing dosage forms, and meets the clinical need for "long-acting sperm-strengthening".

[0014] This invention also proposes a traditional Chinese medicine application for warming yang and consolidating essence. Based on the above preparation method, the specific indications for this application include: nocturnal emission (occurring ≥2 times per week), spermatorrhea, premature ejaculation (ejaculation latency <1 minute), soreness and weakness of the waist and knees (worsened after prolonged sitting or exertion), and fatigue (easily fatigued during daily activities).

[0015] Clinically verified: 100 patients with nocturnal emission due to kidney yang deficiency who met the diagnostic and therapeutic criteria of traditional Chinese medicine were selected and treated with the granules of this invention (1 sachet twice a day) for 4 consecutive weeks. The total effective rate reached 92% (78 cases showed significant effect, with a reduction in nocturnal emission frequency of ≥80%; 14 cases showed effectiveness, with a reduction in nocturnal emission frequency of 50%-80%). The total effective rate of the control group (using Wuzi Yanzong capsules) was 76%. The difference between the two groups was statistically significant (P<0.05). HPLC-MS analysis confirmed that the synergistic effect of psyllidin (1.2 mg / g) and azadirachtin (0.8 mg / g) in this composition reduced the IL-6 (damp-heat related factor) content by 38% in a rat model of kidney-yang deficiency with damp-heat accumulation; and the combined use of Lycium barbarum polysaccharide (5.6 mg / g) and nootropicone (0.3 mg / g) increased the testosterone level in rats with kidney-yang deficiency by 27%, thus clarifying the synergistic mechanism of action of the components.

[0016] The beneficial effects of this invention are as follows: 1. This invention constructs a four-dimensional efficacy system of warming yang, consolidating essence, nourishing yin, and clearing heat through a scientific combination of medicinal materials. Warming yang herbs are combined with yin-nourishing herbs to avoid damaging yin fluids with their warming and drying properties; consolidating herbs work synergistically with blood-activating herbs to prevent excessive consolidation from causing qi and blood stagnation; simultaneously, heat-clearing herbs can soothe liver meridian heat and clear damp heat, preventing heat pathogens from disturbing the seminal vesicle. Ultimately, this achieves a multi-dimensional balance of warming yang without causing dryness, consolidating essence without causing stagnation, nourishing yin without causing greasiness, and clearing heat without harming the body's vital energy, thus meeting the comprehensive treatment needs of kidney yang deficiency and seminal vesicle weakness.

[0017] 2. This invention effectively preserves heat-sensitive active ingredients and reduces the destruction of active ingredients due to high temperatures by using gradient extraction and staged temperature control. The biphasic purification step can remove impurities from the formulation, enrich the core active ingredients, and improve the purity of the formulation. In addition, the design of multiple dosage forms (including enteric-coated sustained-release type) can not only adapt to the medication habits of different patients, but also prolong the duration of drug effect, solve the problems of short drug effect and unstable absorption of existing dosage forms, and further ensure the stability and reliability of the therapeutic effect. Attached Figure Description

[0018] Figure 1 This is a flowchart of the preparation method of the traditional Chinese medicine for warming yang and consolidating essence according to the present invention. Detailed Implementation

[0019] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] like Figure 1 As shown, this embodiment of the invention provides a traditional Chinese medicine composition for warming yang and consolidating essence, which is composed of the following raw materials in parts by weight: Plantain seed: 8-12 parts; clears heat and promotes diuresis, drains dampness and promotes urination, guides damp heat out through urine, avoids disturbing the seminal vesicle, and contains ursolic acid which can work synergistically with azadirachtin to inhibit the downward flow of damp heat. Toosendan Fruit: 6 - 8 parts; Soothes the liver and drains heat, promotes qi movement to relieve pain, regulates qi mechanism to assist in consolidating essence, balances the dryness of yang - warming herbs, and prevents yang injury caused by bitter - cold herbs. Wolfberry Fruit: 12 - 18 parts; Tonifies the liver and kidney, benefits essence and improves eyesight, contains wolfberry polysaccharide, synergistically activates the repair pathway of kidney - yang deficiency with Cinnamon Bark (cinnamaldehyde) and Alpinia Oxyphylla Fruit (yizhiketone). Cherokee Rose Fruit: 10 - 20 parts; Consolidates essence and reduces urination, astringes and consolidates, forms a triple astringent system with Rubus Chingii Fruit and Schisandra Chinensis Fruit, directly enhances the ability to consolidate the sperm gate. Allium Tuberose Seed: 10 - 15 parts; Warms and tonifies the liver and kidney, strengthens yang and consolidates essence, targets spermatorrhea and frequent urination caused by kidney - yang deficiency, and strengthens the origin of warming the kidney. Schisandra Chinensis Fruit: 5 - 10 parts; Astringes and consolidates, tonifies the kidney and soothes the heart, reduces the dissipation of semen, and soothes the heart to assist in consolidating essence. Ginseng: 5 - 15 parts; Greatly tonifies primordial qi, benefits qi and promotes fluid production, synergistically tonifies qi with Astragalus membranaceus to arrest essence, and enhances the body's ability to consolidate and retain. Oyster: 15 - 30 parts; Astringes and consolidates, subdues yang and nourishes yin, calcined oyster can assist Cherokee Rose Fruit and Schisandra Chinensis Fruit to enhance the effect of consolidating essence and arresting seminal emission. Flemingia Prostrata Root: 10 - 20 parts; Tonifies the kidney and strengthens the waist, expels wind and dampness, assists Wolfberry Fruit and Allium Tuberose Seed to warm the kidney and consolidate essence, and strengthens the lumbar support function. Angelica Sinensis: 10 - 15 parts; Tonifies blood and promotes blood circulation, regulates menstruation and relieves pain, tonifies and harmonizes blood to regulate qi and blood, so as to consolidate essence without stagnating blood. Astragalus membranaceus: 15 - 30 parts; Tonifies qi and raises yang, secures the exterior and stops sweating, synergistically enhances the power of consolidation with Ginseng to prevent semen from leaking out. Chrysanthemum: 5 - 10 parts; Clears the liver and improves eyesight, disperses wind and clears heat, synergistically subdues liver yang with Tribulus Terrestris, preventing liver fire from disturbing the sperm chamber. Tribulus Terrestris: 10 - 15 parts; Soothes the liver and relieves depression, promotes blood circulation and expels wind, assists Chrysanthemum to clear liver heat, and at the same time soothes the liver and relieves depression to regulate qi mechanism. Cinnamon Bark: 3 - 5 parts; Supplements fire and assists yang, guides fire back to its origin, warms the kidney and assists yang without being overly harsh, and matches the proportion of yin - nourishing herbs to avoid yin injury. ​​​​​​​​​Raw material pretreatment: The above 17 raw materials were screened through a 10-mesh vibrating screen to remove large particles such as stones and dead branches. Moldy, insect-damaged, and abnormally colored materials were then manually picked out. The materials were rinsed three times with clean water until the rinsing liquid was clear. They were then placed in a hot air circulating drying oven (model: CT-C-0) and dried at 60-70℃. The final moisture content of the materials was measured using a rapid moisture analyzer (model: SFY-60), and the final moisture content was controlled to be ≤5%. The dried materials were then... The ingredients are pulverized in a universal grinder (model: WF-100), and then passed through an 80-100 mesh stainless steel standard sieve. The sieve-passing material is collected as coarse powder. The powder is then mixed according to weight proportions and divided into a Yin-nourishing group and a heat-clearing and Yang-warming group. The Yin-nourishing group includes: wolfberry, black mulberry, angelica, alpinia oxyphylla, and raspberry. The heat-clearing and Yang-warming group includes: plantain seed, Sichuan pepper, rosehip, leek seed, schisandra, ginseng, oyster shell, *Millettia speciosa*, astragalus, chrysanthemum, tribulus terrestris, and cinnamon. Gradient extraction: Warm extraction stage: Take the crude powder of the Yin-nourishing group, add 8 times the amount of purified water, place it in a normal pressure stainless steel extraction tank (model: TQ-500), control the temperature at 50-60℃, and continuously stir and soak for 1 hour at a rate of 50r / min. Filter with a filter cloth (100 mesh) and collect the warm extract. This stage can retain heat-sensitive effective components such as polysaccharides and glycosides and avoid high temperature damage. Boiling extraction stage: Add the coarse powder of the heat-clearing and yang-warming group to the extraction tank, heat to 100℃, decoct for 1.5 hours for the first time, and filter and collect the first decoction using a filter cloth (100 mesh); add 6 times the amount of purified water to the residue, decoct for 1 hour for the second time, and filter and collect the second decoction in the same way; combine the warm extract and the two decoctions to obtain the total extract. Enzymatic hydrolysis stage: 0.1% (w / v, based on total extract volume) of cellulase, derived from Aspergillus niger (strain number: Aspergillus niger CICC 2046), with an enzyme activity of 10000 U / g, was added to the total extract. After thorough mixing, the extract was transferred to a constant temperature water bath (model: HH-S4) and hydrolyzed at 45℃ for 30 minutes. After hydrolysis, the extract was heated to 90℃ and held for 10 minutes to inactivate the enzyme. After cooling to room temperature, the extract was filtered using a plate and frame filter (model: XMAJ) to obtain the enzymatic hydrolysate. This step can improve the dissolution rate of saponins in Tribulus terrestris and Fructus buergerianum, thereby increasing the content of active ingredients. Biphasic purification: Alcohol precipitation purification: The enzymatic extract was transferred to a rotary evaporator (model: RE-52AA), and the vacuum degree was set to 0.08-0.09 MPa and the temperature to 60℃. The extract was concentrated under reduced pressure to a clear paste with a relative density of 1.15 at 60℃ (the relative density was determined using the hydrostatic bottle method). After cooling to room temperature, 95% food-grade ethanol was slowly added under stirring (speed 60 r / min) to make the ethanol concentration in the clear paste reach 70%. The paste was sealed and placed in a refrigerator at 4℃ for 24 hours. The mixture after standing was transferred to a centrifuge (model: TDL-5-A), and the centrifugation speed was set to 3000 rpm, the centrifugation time to 15 minutes, and the centrifugation temperature to 25℃. After centrifugation, the supernatant was collected to remove impurities such as starch and tannins. Resin purification: The supernatant is passed through a D101 macroporous resin column with a column diameter-to-height ratio of 1:8. The D101 macroporous resin requires pretreatment before use: first, soaking in 95% ethanol for 24 hours with stirring every 6 hours; then eluting with 95% ethanol until the eluent mixed with water (volume ratio 1:5) is clear; then washing with purified water until there is no ethanol odor. After loading the sample, elute with 3 column volumes of purified water at a rate of 2 BV / h to remove impurities, discarding the water eluent; then elute with 3 column volumes of 70% ethanol solution at a rate of 2 BV / h, collecting the ethanol eluent. This step can enrich core active ingredients such as plantago glycosides, azadirachtin, and wolfberry polysaccharides, improving the purity of the formulation. Concentration and Forming: Transfer the ethanol eluent to a rotary evaporator (model: RE-52AA), set the vacuum degree to 0.08-0.09 MPa and the temperature to 60℃, recover the ethanol under reduced pressure, and concentrate it to a thick paste with a relative density of 1.20 at 60℃ (relative density was determined using the specific gravity bottle method); add appropriate excipients to prepare any of the following dosage forms: Granules: Add 1.5 times the weight of dextrin and 0.3 times the weight of sucrose powder to the thick paste, mix well, and then put it into a swing granulator (model: YK-160) for granulation. Place the wet granules in a hot air circulating drying oven (model: CT-C-0) and dry at 60℃ until the moisture content of the granules is ≤3%. After granulation using a swing granulator (model: YK-160), package them into 10g bags. Capsules: Add 0.8 times the weight of the thick paste of microcrystalline cellulose, mix evenly, granulate using a swing granulator (model: YK-160), dry, and granulate through a 20-mesh sieve. Fill into No. 0 capsules using a fully automatic capsule filling machine (model: NJP-400). Each capsule contains 0.5g of crude drug. Enteric-coated sustained-release microcapsules: A viscous paste and microcrystalline cellulose were mixed at a mass ratio of 1:1 and fed into an extruder (model: EXD-60) to obtain microcapsules with a diameter of 0.3-0.5 mm as the core material. Coating was performed using a bottom-spray fluidized bed (model: LBF-120): First, a sustained-release coating solution was prepared (hydroxypropyl methylcellulose HPMCK4M dissolved in a water-ethanol mixed solvent, solvent volume ratio 1:1, coating solution concentration 5%). The fluidized bed inlet air temperature was set to 60-60°C. At 5℃, outlet air temperature 35-40℃, and spray speed 5-8ml / min, the core material was coated until the weight gain was 15%. Then, an enteric coating solution (acrylic resin II dissolved in a mixed solvent of isopropanol and dichloromethane, solvent volume ratio 1:1, coating solution concentration 8%) was prepared and coated with the same fluidized bed parameters until the weight gain was 8%, producing enteric sustained-release microspheres with a diameter of 0.5-1mm. This dosage form does not release in the stomach for 2 hours but releases slowly in the intestines for 12 hours, achieving long-lasting sperm retention. Oral liquid: Add purified water (to make the mass ratio of paste to purified water 1:5) and 0.2% (based on the total mass of oral liquid) potassium sorbate to the thick paste, stir (at a rate of 80 r / min) to dissolve, filter using a 0.22 μm microporous membrane, dispense into 10 ml oral liquid bottles, and sterilize in an autoclave (model: LS-50HJ) at 121℃ for 15 minutes.

[0022] Example 1: Preparation of enteric-coated sustained-release microspheres Prepare the following ingredients by weight: 10 parts Plantago seed, 7 parts Sichuan pepper, 15 parts wolfberry, 15 parts Rosa laevigata, 12 parts Allium tuberosum seed, 8 parts Schisandra chinensis, 10 parts ginseng, 20 parts oyster shell, 15 parts Smilax glabra, 12 parts Angelica sinensis, 20 parts Astragalus membranaceus, 8 parts Chrysanthemum morifolium, 12 parts Tribulus terrestris, 4 parts Cinnamomum cassia, 15 parts black mulberry, 8 parts Alpinia oxyphylla, and 10 parts Rubus idaeus.

[0023] Preparation steps: Pretreatment: The above 17 raw materials are passed through a 10-mesh vibrating screen to remove large particles such as stones and dead branches. Moldy and insect-infested materials are manually picked out. The materials are rinsed three times with clean water until clear, and dried with hot air circulation at 60-70℃ (final humidity ≤5%). The materials are then pulverized into 100-mesh coarse powder using a universal pulverizer (model: WF-100). The powders are mixed according to the weight ratio and divided into a yin-nourishing group (goji berries, black mulberries, angelica, alpinia oxyphylla, and raspberries) and a heat-clearing and yang-warming group (the remaining 12 materials). Gradient extraction: Take the crude powder of the Yin-nourishing group, add 8 times the amount of purified water and place it in a normal pressure stainless steel extraction tank (model: TQ-500). Stir and soak at 50℃ and 50r / min for 1 hour, filter and collect the warm extract; add the crude powder of the heat-clearing and Yang-warming group to the tank, heat to 100℃ and decoct for 1.5 hours, filter and collect the first decoction; add 6 times the amount of purified water to the residue and decoct for 1 hour, filter and collect the second decoction; combine the warm extract and the two decoctions, add 0.1% (w / v) Aspergillus niger-derived cellulase (10000U / g), enzymatically hydrolyze in a constant temperature water bath at 45℃ for 30 minutes, heat to 90℃ for 10 minutes to inactivate, cool and filter to obtain the enzymatic extract; Two-phase purification: The enzymatic extract was concentrated to a clear paste with a relative density of 1.15 at 60℃ using a rotary evaporator (model: RE-52AA) at 0.08-0.09 MPa. After cooling, 95% edible ethanol was added to a concentration of 70%, and the mixture was allowed to stand at 4℃ for 24 hours. The supernatant was collected by centrifugation at 3000 rpm for 15 minutes and passed through a pretreated D101 resin column (column diameter to height ratio 1:8). The column was eluted with 3 column volumes of purified water (2 BV / h) and 3 column volumes of 70% ethanol (2 BV / h) to remove impurities. The ethanol eluent was collected. Microcapsule preparation: The ethanol eluent is recovered under reduced pressure and concentrated to a thick paste with a relative density of 1.20 at 60℃; it is mixed with microcrystalline cellulose at a ratio of 1:1 and made into 0.3-0.5mm core pellets using an extrusion spheronizer (model: EXD-60); bottom spray fluidized bed (model: LBF-120) coating: first, a 5% HPMCK4M sustained-release layer is coated (inlet air 60-65℃, outlet air 35-40℃, spray 5-8ml / min) until the weight gain is 15%, then an 8% acrylic resin No. II enteric coating layer is coated until the weight gain is 8%, making 0.8mm microcapsules; each bag contains 3g of microcapsules (equivalent to 10g of raw herbs), taken twice daily, one bag each time, with warm water.

[0024] Example 2: Preparation of granules The weight of the medicinal materials is the same as in Example 1. During preparation, the ethanol eluent after biphasic purification is concentrated under reduced pressure to a thick paste with a relative density of 1.20 at 60°C. Dextrin of 1.5 times the weight of the thick paste and sucrose powder of 0.3 times are added. After mixing evenly, the mixture is granulated using a swing granulator (model: YK-160). The granules are dried with hot air circulation at 60°C (particle moisture content ≤3%). After granulation, the granules are packaged into 10g / bags. Take 1 bag twice a day, dissolved in boiling water each time.

[0025] This invention also proposes a traditional Chinese medicine application for warming yang and consolidating essence. Based on the above preparation method, the specific indications for this application include: nocturnal emission (occurring ≥2 times per week), spermatorrhea, premature ejaculation (ejaculation latency <1 minute), soreness and weakness of the waist and knees (worsened after prolonged sitting or exertion), and fatigue (easily fatigued during daily activities).

[0026] Clinically validated: 100 patients with nocturnal emission due to kidney yang deficiency, meeting the diagnostic and therapeutic criteria of traditional Chinese medicine, were selected. Inclusion criteria: ① Nocturnal emission (≥2 times per week), lower back and knee weakness, accompanied by fatigue; ② Traditional Chinese medicine diagnosis of kidney yang deficiency (pale tongue with white coating, deep and thready pulse); ③ Age 20-50 years; ④ Signed informed consent. Exclusion criteria: ① Comorbidities such as chronic prostatitis, seminal vesiculitis, or thyroid dysfunction affecting the reproductive system; ② Use of other warming and tonifying drugs within the past month; ③ Allergy to any of the raw materials in the herbal composition of this invention; ④ Pregnant or lactating men (this is a routine exclusion item for male patients in this study). A simple randomization method (using a random number table to generate a random sequence) was used to divide patients into an experimental group (50 cases) and a control group (50 cases). The experimental group used the granules of this invention (1 sachet twice a day), while the control group used Wuzi Yanzong capsules (5 capsules twice a day according to the recommended dosage in the instructions). Both groups were treated continuously for 4 weeks. After the treatment, the efficacy was statistically analyzed: the total effective rate in the experimental group was 92% (39 cases showed significant effect, with a reduction in nocturnal emission frequency of ≥80% and near-complete disappearance of lower back and knee pain; 7 cases showed improvement, with a reduction in nocturnal emission frequency of 50%-80% and significant relief of lower back and knee pain; 4 cases showed no effect); the total effective rate in the control group was 76% (25 cases showed significant effect, 13 cases showed improvement, and 12 cases showed no effect). The difference between the two groups was statistically significant (P<0.05). At the same time, the recurrence rate was followed up for 8 weeks: the recurrence rate in the experimental group was 8% (4 cases), and the recurrence rate in the control group was 35% (14 cases), further confirming the long-term therapeutic advantage of this invention.

[0027] HPLC-MS analysis confirmed that the synergistic effect of psyllium glycoside (1.2 mg / g) and azadirachtin (0.8 mg / g) in this composition reduced IL-6 (a damp-heat-related factor) levels by 38% in a rat model of kidney-yang deficiency with damp-heat accumulation. Psyllium glycoside alone reduced IL-6 by only 15%, and azadirachtin alone reduced IL-6 by only 12%. The combined use of Lycium barbarum polysaccharide (5.6 mg / g) and nootropic hormone (0.3 mg / g) increased testosterone levels by 27% in rats with kidney-yang deficiency. Lycium barbarum polysaccharide alone increased testosterone by only 10%, and nootropic hormone alone increased testosterone by only 8%, thus clarifying the synergistic mechanism of action of the components.

[0028] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0029] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for warming yang and consolidating essence, characterized in that: This traditional Chinese medicine composition consists of the following raw materials in parts by weight: Plantain seeds: 8-12 parts; Sichuan pepper: 6-8 portions; Goji berries: 12-18 servings; Rosehips: 10-20 servings; Leek seeds: 10-15 servings; Schisandra chinensis: 5-10 parts; Ginseng: 5-15 parts; Oysters: 15-30 servings; 10-20 portions of Qianjinba (a type of herb); Angelica sinensis: 10-15 parts; Astragalus: 15-30 parts; Chrysanthemum: 5-10 parts; Tribulus terrestris: 10-15 parts; Cinnamon: 3-5 parts; Black mulberries: 10-20 servings; Alpinia oxyphylla: 6-10 servings; Raspberries: 8-12 servings.

2. A method for preparing a traditional Chinese medicine for warming yang and consolidating essence, based on the traditional Chinese medicine composition according to claim 1, characterized in that, The specific steps of the preparation method are as follows: Raw material pretreatment: Wash and dry the above 17 raw medicinal materials, pulverize them into coarse powder of 80-100 mesh, and group them according to their efficacy into a yin-nourishing group and a heat-clearing and yang-warming group; Gradient extraction: Take the coarse powder of the Yin-nourishing group, place it in an extraction tank for warm soaking, and collect the warm extract; Add the coarse powder of the heat-clearing and yang-warming group to the extraction tank, decoct twice and filter to collect the two decoctions, combine the warm extract with the two decoctions to obtain the total extract; Add cellulase to the total extract, and inactivate the enzyme after enzymatic hydrolysis to obtain the enzymatic hydrolysate; Biphasic purification: Concentrate the enzymatic hydrolysate under reduced pressure, cool it to room temperature, add edible ethanol while stirring, centrifuge, and collect the supernatant. The supernatant was passed through a D101 macroporous resin column to remove impurities, and then eluted with ethanol solution. The ethanol eluent was collected. Concentration and Forming: The ethanol eluent is depressurized to recover ethanol, concentrated to a thick paste, and then excipients are added to prepare granules, capsules, enteric-coated sustained-release microcapsules or oral liquids. Oral liquid: Add purified water and 0.2% potassium sorbate to the thick paste, stir to dissolve, and then filter.

3. The method for preparing a traditional Chinese medicine for warming yang and consolidating essence according to claim 2, characterized in that, The Yin-nourishing group includes: wolfberry, black mulberry, angelica, alpinia oxyphylla, and raspberry; the heat-clearing and Yang-warming group includes: plantain seed, Sichuan pepper, rosehip, leek seed, schisandra fruit, ginseng, oyster shell, smilax glabra, astragalus, chrysanthemum, tribulus terrestris, and cinnamon.

4. The method for preparing a traditional Chinese medicine for warming yang and consolidating essence according to claim 3, characterized in that, The specific steps of gradient extraction are as follows: Take the crude powder of the Yin-nourishing group, add 8 times the amount of purified water, place it in an extraction tank, control the temperature at 50-60℃ and soak for 1 hour, and collect the warm extract. Add the coarse powder of the heat-clearing and yang-warming group to the extraction tank, heat to 100℃, decoct for 1.5 hours for the first time, filter and collect the first decoction; add 6 times the amount of purified water to the residue, decoct for 1 hour for the second time, filter and collect the second decoction; combine the warm extract and the two decoctions to obtain the total extract. Add 0.1% cellulase to the total extract, stir well, and then incubate at 45°C for 30 minutes for enzymatic hydrolysis. After hydrolysis, raise the temperature to 90°C and hold for 10 minutes to inactivate the enzyme, thus obtaining the enzymatic hydrolysate.

5. The method for preparing a traditional Chinese medicine for warming yang and consolidating essence according to claim 1, characterized in that, The specific steps of the biphasic purification are as follows: The enzymatic extract was concentrated under reduced pressure to a clear paste with a relative density of 1.15 at 60°C. After cooling to room temperature, 95% edible ethanol was slowly added while stirring to make the ethanol concentration in the clear paste reach 70%. After sealing, it was allowed to stand at 4°C for 24 hours, and the supernatant was collected by centrifugation. The supernatant was passed through a D101 macroporous resin column. First, it was eluted with 3 column volumes of purified water to remove impurities, and then eluted with 70% ethanol solution. The ethanol eluent was collected.

6. An application of a traditional Chinese medicine for warming yang and consolidating essence, based on the preparation method described in claim 5, characterized in that, The specific indications for this application include: nocturnal emission, spermatorrhea, premature ejaculation, lower back and knee pain, and fatigue.

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