Combination medicine for treating chronic prostatitis and preparation method thereof

Abstract

The invention discloses a combined medicine for treating chronic prostatitis and a preparation method thereof. Comprising the following active components in percentage by mass: 12%-18% of tanshinone IIA, 18%-22% of cortex phellodendri total alkaloids, 25%-30% of astragalus polysaccharide, 10%-15% of taraxacin, 8%-12% of ligustrazine, 4%-6% of spina date seed total saponins, 2%-4% of schizandrin and 1%-3% of glycyrrhizic acid. The tanshinone IIA, the amur corktree bark total alkaloids and the taraxacin in the combined medicine are used for inhibiting expression of inflammatory factors such as COX-2, TNF-alpha and IL-6, so that prostate tissue inflammatory response is directly blocked; meanwhile, the astragalus polysaccharide and glycyrrhizic acid cooperate to activate T lymphocyte subgroups, regulate Th1 / Th2 balance and enhance the immune defense capability of the body, so that the recurrence rate is reduced.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a combination drug for treating chronic prostatitis and its preparation method. Background Technology

[0002] Chronic prostatitis is a common male urogenital disease, referring to chronic inflammation of the prostate tissue. It has a long course and is prone to recurrence, seriously affecting the patient's quality of life. Chronic prostatitis is a common disease of the male urinary system, with an incidence rate as high as 50%. It is mainly manifested as pelvic pain, abnormal urination and sexual dysfunction. Its etiology is complex, involving inflammatory response, immune imbalance, local blood circulation disorders and neuromuscular dysfunction.

[0003] Existing medications for treating chronic prostatitis have limitations. Traditional drugs target only a single pathological aspect, making it difficult to comprehensively improve symptoms. This can easily lead to recurring symptoms and severely impact patients' quality of life. Patients with chronic prostatitis are prone to anxiety, depression, and other emotional problems due to long-term pain, difficulty urinating, and sexual dysfunction.

[0004] Therefore, we propose a combination drug for treating chronic prostatitis and its preparation method. Summary of the Invention

[0005] The purpose of this invention is to provide a combination drug for treating chronic prostatitis and its preparation method, thereby solving the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a combination drug for treating chronic prostatitis, comprising the following active ingredients in the following mass percentages: tanshinone IIA 12%-18%, total alkaloids of Phellodendron bark 18%-22%, Astragalus polysaccharide 25%-30%, dandelion saponins 10%-15%, ligustrazine 8%-12%, total saponins of jujube seed 4%-6%, schisandrin A 2%-4%, and glycyrrhizic acid 1%-3%;

[0007] The combination drugs improve prostate blood circulation and promote the discharge of inflammatory secretions through multi-target synergistic effects, and also have anti-inflammatory, analgesic, immunomodulatory and mood-soothing functions.

[0008] As a preferred embodiment of the present invention, the active ingredients are composed of the following active ingredients in the following mass percentages: tanshinone IIA 15%, total alkaloids of Phellodendron bark 20%, Astragalus polysaccharide 28%, dandelion saponins 12%, ligustrazine 10%, total saponins of jujube seed 5%, schisandrin A 3%, and glycyrrhizic acid 2%.

[0009] As a preferred embodiment of the present invention, the active ingredients are composed of the following active ingredients in the following mass percentages: tanshinone IIA 18%, total alkaloids of Phellodendron bark 18%, Astragalus polysaccharide 30%, dandelion saponins 10%, ligustrazine 12%, total saponins of jujube seed 4%, schisandrin A 4%, and glycyrrhizic acid 1%.

[0010] As a preferred embodiment of the present invention, the ingredients are: tanshinone IIA 12%, total alkaloids of Phellodendron bark 22%, Astragalus polysaccharide 25%, dandelion saponins 15%, ligustrazine 8%, total saponins of jujube seed 6%, schisandrin A 2%, and glycyrrhizic acid 3%.

[0011] This invention also relates to a method for preparing a combination drug for treating chronic prostatitis, comprising the following steps:

[0012] Step 1: Raw material pretreatment: Grind the following ingredients into powder to 200 mesh and dry them under low temperature vacuum (50℃, -0.08MPa): Salvia miltiorrhiza, Phellodendron chinense, Astragalus membranaceus, Taraxacum mongolicum, Ligusticum chuanxiong, Ziziphus jujuba var. spinosa, and Schisandra chinensis.

[0013] Step 2: Multi-stage extraction: Salvia miltiorrhiza and Ligusticum chuanxiong were extracted using a combination of ultrasound and enzymatic hydrolysis for 2 hours at 50°C. Phellodendron amurense and Schisandra chinensis were extracted using supercritical CO2 at 25 MPa at 40°C. Astragalus membranaceus, Taraxacum mongolicum, and Ziziphus jujuba var. spinosa were purified using membrane separation with ceramic membranes having pore sizes of 10 kDa and 1 kDa, respectively. Glycyrrhiza uralensis was adsorbed using macroporous resin D101 with 50% ethanol as the eluent.

[0014] Step 3: Formulation: Mix the extracts in proportion, add 10% microcrystalline cellulose, 5% hydroxypropyl methylcellulose and mannitol-trehalose (1:1) as stabilizers, wet granulate, dry at 60℃ and then compress or package.

[0015] In a preferred embodiment of the present invention, the purity of the total saponins of jujube seed is ≥90%, the purity of schisandrol A is ≥95%, and the purity of glycyrrhizic acid is ≥90%.

[0016] In a preferred embodiment of the present invention, in the ultrasound-enzyme hydrolysis combined extraction step, the enzymatic hydrolysis time is extended to 2.5 h and the enzymatic hydrolysis temperature is adjusted to 55 °C to improve the extraction rate of tanshinone IIA.

[0017] In a preferred embodiment of the present invention, in the supercritical CO2 extraction step, the extraction pressure is adjusted to 30 MPa and the extraction time is extended to 2.5 h to improve the purity of Phellodendron alkaloids and schisandrol A.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0019] This invention utilizes a combination of tanshinone IIA, total alkaloids from Phellodendron bark, and dandelion saponins to directly block the inflammatory response in prostate tissue by inhibiting the expression of inflammatory factors such as COX-2, TNF-α, and IL-6. Simultaneously, astragalus polysaccharides and glycyrrhizic acid synergistically activate T lymphocyte subsets, regulate the Th1 / Th2 balance, enhance the body's immune defense capabilities, and help reduce the recurrence rate.

[0020] Ligustrazine increases prostate blood flow velocity by 35%-50% by inhibiting platelet aggregation and dilating local blood vessels; the combined action of total saponins from jujube seed and schisandrol A can reduce capillary permeability and promote the discharge of purulent secretions from glandular ducts, thereby helping to improve local hypoxia.

[0021] Total saponins from jujube seed and schisandrol A can help improve patients' anxiety by regulating GABA receptors and 5-HT reuptake. Tanshinone IIA and ligustrazine have analgesic effects, thus achieving holistic treatment of both mind and body, which can further enhance the therapeutic effect.

[0022] The extraction rate of tanshinone IIA was improved by using a combination of ultrasonic and enzymatic extraction technology; the purity of Phellodendron amurense alkaloids was improved by supercritical CO2 extraction process, avoiding organic solvent residue; and membrane separation purification technology concentrated the molecular weight distribution of Astragalus polysaccharides in the range of 10-50 kDa, thereby enhancing their immune activity. Attached Figure Description

[0023] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:

[0024] Figure 1 This is a flowchart illustrating the operation of a combination drug for treating chronic prostatitis and its preparation method according to the present invention. Detailed Implementation

[0025] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.

[0026] Example 1

[0027] Combination drug formulation:

[0028] Tanshinone IIA 15%, total alkaloids of Phellodendron bark 20%, polysaccharides of Astragalus membranaceus 28%, dandelion saponins 12%, ligustrazine 10%, total saponins of Ziziphus jujuba seed 5%, schisandrin A 3%, and glycyrrhizic acid 2%.

[0029] Preparation method:

[0030] Raw material pretreatment: The danshen, phellodendron bark, astragalus, dandelion, chuanxiong, jujube seed, and schisandra fruit were pulverized to 200 mesh and dried under low temperature vacuum (50℃, -0.08MPa).

[0031] Multi-stage extraction: Salvia miltiorrhiza and Ligusticum chuanxiong were extracted using a combination of ultrasound and enzymatic hydrolysis for 2.5 h at 55 °C. Phellodendron amurense and Schisandra chinensis were extracted using supercritical CO2 at 30 MPa at 40 °C for 2.5 h. Astragalus membranaceus, Taraxacum mongolicum, and Ziziphus jujuba var. spinosa were purified using membrane separation with ceramic membranes having pore sizes of 10 kDa and 1 kDa, respectively. Glycyrrhiza uralensis was adsorbed using macroporous resin D101 with 50% ethanol as the eluent.

[0032] Formulation: The extracts were mixed in proportion, and 10% microcrystalline cellulose, 5% hydroxypropyl methylcellulose and mannitol-trehalose (1:1) were added as stabilizers. The mixture was wet granulated, dried at 60°C and then tableted.

[0033] Example 2

[0034] Composition formulation:

[0035] Tanshinone IIA 18%, total alkaloids of Phellodendron bark 18%, polysaccharides of Astragalus membranaceus 30%, dandelion saponins 10%, ligustrazine 12%, total saponins of Ziziphus jujuba seed 4%, schisandrin A 4%, and glycyrrhizic acid 1%.

[0036] Preparation method:

[0037] Raw material pretreatment: The danshen, phellodendron bark, astragalus, dandelion, chuanxiong, jujube seed, and schisandra fruit were pulverized to 200 mesh and dried under low temperature vacuum (50℃, -0.08MPa).

[0038] Multi-stage processing: Salvia miltiorrhiza and Ligusticum chuanxiong were extracted using a combination of ultrasound and enzymatic hydrolysis for 2 hours at 50°C. Phellodendron amurense and Schisandra chinensis were extracted using supercritical CO2 at 25 MPa at 40°C. Astragalus membranaceus, Taraxacum mongolicum, and Ziziphus jujuba var. spinosa were purified using membrane separation with ceramic membranes having pore sizes of 10 kDa and 1 kDa, respectively. Glycyrrhiza uralensis was adsorbed using macroporous resin D101 with 50% ethanol as the eluent.

[0039] Formulation: The extracts were mixed in proportion, and 10% microcrystalline cellulose, 5% hydroxypropyl methylcellulose and mannitol-trehalose (1:1) were added as stabilizers. The mixture was wet granulated, dried at 60°C and then tableted.

[0040] Example 3

[0041] Combination drug formulation:

[0042] Tanshinone IIA 12%, total alkaloids of Phellodendron bark 22%, polysaccharides of Astragalus membranaceus 25%, dandelion saponins 15%, ligustrazine 8%, total saponins of Ziziphus jujuba seed 6%, schisandrin A 2%, glycyrrhizic acid 3%.

[0043] Preparation method:

[0044] Raw material pretreatment: The danshen, phellodendron bark, astragalus, dandelion, chuanxiong, jujube seed, and schisandra fruit were pulverized to 200 mesh and dried under low temperature vacuum (50℃, -0.08MPa).

[0045] Multi-stage processing: Salvia miltiorrhiza and Ligusticum chuanxiong were extracted using a combination of ultrasound and enzymatic hydrolysis, with the hydrolysis time extended to 2.5 h and the hydrolysis temperature adjusted to 55 °C. Phellodendron amurense and Schisandra chinensis were extracted using supercritical CO2 extraction, with the extraction pressure adjusted to 30 MPa and the extraction time extended to 2.5 h. Astragalus membranaceus, Taraxacum mongolicum, and Ziziphus jujuba var. spinosa were purified using membrane separation with ceramic membranes having pore sizes of 10 kDa and 1 kDa, respectively. Glycyrrhiza uralensis was adsorbed using macroporous resin, with resin type D101 and 50% ethanol as the eluent.

[0046] Formulation: The extracts were mixed in proportion, and 10% microcrystalline cellulose, 5% hydroxypropyl methylcellulose and mannitol-trehalose (1:1) were added as stabilizers. The mixture was wet granulated, dried at 60°C and then tableted.

[0047] Comparative Example

[0048] Combination drug formulation:

[0049] The total alkaloids of Phellodendron bark are 50%, and the excipients are 50%.

[0050] Preparation method:

[0051] Raw material pretreatment: Phellodendron bark is pulverized to 200 mesh and dried under low temperature vacuum (50℃, -0.08MPa).

[0052] Extraction: Phellodendron bark was extracted using supercritical CO2 at an extraction pressure of 25 MPa and an extraction temperature of 40℃.

[0053] Formulation: The extract and excipients are mixed, wet granulated, dried at 60°C, and then compressed into tablets.

[0054] The data obtained from the experiments conducted on the three embodiments and comparative examples are shown in the table below:

[0055]

[0056] In summary, this invention directly blocks the inflammatory response in prostate tissue by inhibiting the expression of inflammatory factors such as COX-2, TNF-α, and IL-6 through the combination of tanshinone IIA, total alkaloids of Phellodendron bark, and dandelion saponins in the combined drug; at the same time, astragalus polysaccharide and glycyrrhizic acid synergistically activate T lymphocyte subsets, regulate the Th1 / Th2 balance, enhance the body's immune defense capabilities, and help reduce the recurrence rate.

[0057] Ligustrazine increases prostate blood flow velocity by 35%-50% by inhibiting platelet aggregation and dilating local blood vessels; the combined action of total saponins from jujube seed and schisandrol A can reduce capillary permeability and promote the discharge of purulent secretions from glandular ducts, thereby helping to improve local hypoxia.

[0058] Total saponins from jujube seed and schisandrol A can help improve patients' anxiety by regulating GABA receptors and 5-HT reuptake. Tanshinone IIA and ligustrazine have analgesic effects, thus achieving holistic treatment of both mind and body, which can further enhance the therapeutic effect.

[0059] The extraction rate of tanshinone IIA was improved by using a combination of ultrasonic and enzymatic extraction technology; the purity of Phellodendron amurense alkaloids was improved by supercritical CO2 extraction process, avoiding organic solvent residue; and membrane separation purification technology concentrated the molecular weight distribution of Astragalus polysaccharides in the range of 10-50 kDa, thereby enhancing their immune activity.

[0060] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or basic characteristics. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

[0061] In addition, it should be understood that although this specification is described in terms of implementation methods, not every implementation method contains only one independent technical solution. This narrative method of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment can also be appropriately combined to form other implementation methods that can be understood by those skilled in the art.

Claims

1. A combination drug for treating chronic prostatitis, characterized in that: It is composed of the following active ingredients in the following percentages by mass: Tanshinone IIA 12%-18%, total alkaloids of Phellodendron bark 18%-22%, Astragalus polysaccharide 25%-30%, dandelion saponins 10%-15%, tetramethylpyrazine 8%-12%, total saponins of Ziziphus jujuba seed 4%-6%, schisandrol A 2%-4%, and glycyrrhizic acid 1%-3%; The combination drugs improve prostate blood circulation and promote the discharge of inflammatory secretions through multi-target synergistic effects, and also have anti-inflammatory, analgesic, immunomodulatory and mood-soothing functions.

2. The combination drug for treating chronic prostatitis according to claim 1, characterized in that: It is composed of the following active ingredients in the following percentage by mass: Tanshinone IIA 15%, total alkaloids of Phellodendron bark 20%, Astragalus polysaccharide 28%, taraxacin 12%, tetramethylpyrazine 10%, total saponins of jujube seed 5%, schisandrin A 3%, and glycyrrhizic acid 2%.

3. The combination drug for treating chronic prostatitis according to claim 1, characterized in that: It is composed of the following active ingredients in the following percentage by mass: Tanshinone IIA 18%, total alkaloids of Phellodendron bark 18%, Astragalus polysaccharide 30%, dandelion saponins 10%, tetramethylpyrazine 12%, total saponins of jujube seed 4%, schisandrin A 4%, and glycyrrhizic acid 1%.

4. The combination drug for treating chronic prostatitis according to claim 1, characterized in that: Tanshinone IIA 12%, total alkaloids of Phellodendron bark 22%, polysaccharides of Astragalus membranaceus 25%, dandelion saponins 15%, ligustrazine 8%, total saponins of Ziziphus jujuba seed 6%, schisandrin A 2%, glycyrrhizic acid 3%.

5. A method for preparing a combination drug for treating chronic prostatitis, applicable to the combination drug for treating chronic prostatitis according to any one of claims 1-4, characterized in that, Includes the following steps: Step 1: Raw material pretreatment: Pulverize Salvia miltiorrhiza, Phellodendron chinense, Astragalus membranaceus, Taraxacum mongolicum, Ligusticum chuanxiong, Ziziphus jujuba var. spinosa, and Schisandra chinensis to 200 mesh and dry under low temperature vacuum (50℃, -0.08MPa); Step 2: Multi-stage extraction: Salvia miltiorrhiza and Ligusticum chuanxiong were extracted using a combination of ultrasound and enzymatic hydrolysis for 2 hours at 50°C. Phellodendron amurense and Schisandra chinensis were extracted using supercritical CO2 at 25 MPa at 40°C. Astragalus membranaceus, Taraxacum mongolicum, and Ziziphus jujuba var. spinosa were purified using membrane separation with ceramic membranes having pore sizes of 10 kDa and 1 kDa, respectively. Glycyrrhiza uralensis was adsorbed using macroporous resin D101 with 50% ethanol as the eluent. Step 3: Formulation: Mix the extracts in proportion, add 10% microcrystalline cellulose, 5% hydroxypropyl methylcellulose and mannitol-trehalose (1:1) as stabilizers, wet granulate, dry at 60℃ and then compress or package.

6. The method for preparing a combination drug for treating chronic prostatitis according to claim 5, characterized in that: The purity of the total saponins from the jujube seed is ≥90%, the purity of schisandrol A is ≥95%, and the purity of glycyrrhizic acid is ≥90%.

7. The method for preparing a combination drug for treating chronic prostatitis according to claim 5, characterized in that: In the ultrasound-enzyme hydrolysis extraction step, the hydrolysis time is extended to 2.5 hours and the hydrolysis temperature is adjusted to 55°C to improve the extraction rate of tanshinone IIA.

8. The method for preparing a combination drug for treating chronic prostatitis according to claim 5, characterized in that: In the supercritical CO2 extraction step, the extraction pressure was adjusted to 30 MPa and the extraction time was extended to 2.5 h to improve the purity of Phellodendron alkaloids and Schisandrin A.

Images