A compound tripterygium composition, oral liquid and preparation method and application thereof

Abstract

The application belongs to the field of traditional Chinese medicine compositions, and specifically discloses a compound tripterygium wilfordii composition, an oral liquid, and a preparation method and application thereof. The compound tripterygium wilfordii composition is composed of the following medicinal materials: monarch drug: tripterygium wilfordii; ministerial drug: astragalus, sanguisorba, ligustrum lucidum, herba tremella; auxiliary drug: caulophyllum inophylum, schisandra; ministerial drug: glycyrrhiza. The application finds that the combination of astragalus, sanguisorba, ligustrum lucidum and herba tremella can effectively reduce the side effects caused by tripterygium wilfordii and improve the treatment effect of tripterygium wilfordii. The oral liquid prepared from the above compound composition effectively improves the treatment effect of chronic glomerulonephritis and significantly reduces the side effects of tripterygium wilfordii, and is suitable for chronic kidney disease patients who need long-term treatment, helps them to improve symptoms and improve the quality of life, and at the same time reduces the risk brought by drug side effects.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine compositions, and specifically discloses a compound Tripterygium wilfordii composition, an oral liquid, its preparation method, and its application. Background Technology

[0002] Tripterygium wilfordii is a widely used herb in traditional Chinese medicine, primarily for treating autoimmune diseases such as rheumatoid arthritis and chronic glomerulonephritis. Despite its significant therapeutic effects, its severe side effects limit its wider clinical application.

[0003] Tripterygium wilfordii contains various bioactive components, such as triptolide and triptolide, which have shown good therapeutic effects on chronic glomerulonephritis. These components can effectively improve the pathological state of the kidneys, reduce proteinuria, and protect kidney function through anti-inflammatory and immunomodulatory effects.

[0004] While Tripterygium wilfordii has significant therapeutic effects, its side effects are equally serious, including: leukopenia: Due to its effects on the immune system, the use of Tripterygium wilfordii may lead to leukopenia, increasing the risk of infection; abnormal liver function: Tripterygium wilfordii may cause abnormal liver function, such as elevated liver enzyme levels, requiring regular liver function tests; irregular menstruation and amenorrhea: Female patients using Tripterygium wilfordii may experience irregular menstrual cycles or amenorrhea; reproductive system side effects: Male patients may experience reproductive system side effects, such as asthenospermia or azoospermia, affecting fertility. Summary of the Invention

[0005] Based on the shortcomings of existing technologies, this invention discloses a compound Tripterygium wilfordii composition, oral liquid, its preparation method and application. By combining Astragalus membranaceus, Sanguisorba officinalis, Ligustrum lucidum and Eclipta prostrata, the side effects caused by Tripterygium wilfordii alone are effectively reduced and the therapeutic effect of Tripterygium wilfordii is improved.

[0006] This invention includes the following technical solutions:

[0007] A compound Tripterygium wilfordii composition, comprising the following medicinal materials: principal ingredient: Tripterygium wilfordii; assistant ingredients: Astragalus membranaceus, Sanguisorba officinalis, Ligustrum lucidum, Eclipta prostrata; adjuvant ingredients: Aristolochia debilis, Schisandra chinensis; guiding ingredient: Glycyrrhiza uralensis.

[0008] Furthermore, the aforementioned compound Tripterygium wilfordii composition, by weight, comprises the following medicinal materials:

[0009] Tripterygium wilfordii 10-20 parts, Astragalus membranaceus 20-40 parts, Sanguisorba officinalis 20-40 parts, Ligustrum lucidum 10-20 parts, Eclipta prostrata 10-20 parts, Aristolochia debilis 20-40 parts, Schisandra chinensis 5-15 parts, Glycyrrhiza uralensis 5-15 parts.

[0010] Preferably, the above-mentioned compound Tripterygium wilfordii composition, by weight, consists of the following medicinal materials: 15 parts Tripterygium wilfordii, 30 parts Astragalus membranaceus, 30 parts Sanguisorba officinalis, 15 parts Ligustrum lucidum, 15 parts Eclipta prostrata, 30 parts Achyranthes bidentata, 10 parts Schisandra chinensis, and 10 parts Glycyrrhiza uralensis.

[0011] Furthermore, in the aforementioned compound Tripterygium wilfordii composition, the medicinal material is a traditional Chinese medicine decoction piece.

[0012] Preferably, the preparation method of the above-mentioned compound Tripterygium wilfordii composition includes the following steps:

[0013] 1) Raw material processing: Wash all kinds of medicinal materials, remove impurities, crush them, dry them overnight, weigh them according to the weight parts in the formula and mix them to obtain mixture A;

[0014] (2) Decoction: Add mixture A to 10-20 times its weight of water, soak at 80-90℃ for 2-4 hours, then boil and reflux for 1-2 hours, filter to obtain the medicinal liquid and the residue, add 3-6 times its weight of water to the residue, heat and reflux for 30-60 minutes, combine the filtered medicinal liquid with the medicinal liquid obtained from the first filtration to obtain mixture B;

[0015] (3) Concentration and extraction: Mixture B was concentrated under reduced pressure at -0.07 to -0.08 MPa and 70 to 90°C until the density was 1.1 to 1.2 g / cm³. 3 Mixture C is obtained;

[0016] (4) Vacuum spray drying: The above mixture C is placed in a vacuum spray dryer for vacuum spray drying to obtain mixture D with a moisture content of less than 10%.

[0017] (5) Pre-freezing: Spread the above mixture D out to a thickness of 3-6cm, and perform rapid pre-freezing under normal pressure for 70-90min at a temperature of -30 to -50℃ to obtain mixture E.

[0018] (6) Freeze-drying: Under the condition of maintaining the pre-freezing temperature, add 5-10% by mass of freeze-drying protectant, mix thoroughly with mixture E, and then put it into a freeze dryer for freeze-drying. The freeze-drying procedure is as follows:

[0019] A: -45~-55℃, pressure 500-700Pa, freeze-dry for 45-75min;

[0020] B: -65~-55℃, pressure 120-220Pa, freeze-drying 120-240min;

[0021] C: -75~-85℃, pressure 60-120Pa, freeze-dry for 20-40min;

[0022] D: Return to room temperature and pressure, and dry until the moisture content is below 5%, to obtain mixture F, which is the compound Tripterygium wilfordii composition. Preferably, the freeze-drying protectant is glycerol or chitosan.

[0023] Compared with the prior art, the present invention has the following outstanding advantages:

[0024] This invention discloses a compound Tripterygium wilfordii composition, an oral liquid, its preparation method, and its application. This invention discovers that the combination of Astragalus membranaceus, Sanguisorba officinalis, Ligustrum lucidum, and Eclipta prostrata can effectively reduce the side effects caused by Tripterygium wilfordii alone and improve its therapeutic effect. The oral liquid prepared from the above compound composition effectively improves the therapeutic effect of chronic glomerulonephritis and significantly reduces the side effects of Tripterygium wilfordii. It is suitable for patients with chronic kidney disease requiring long-term treatment, helping them improve symptoms and quality of life while reducing the risks associated with drug side effects. Attached Figure Description

[0025] Figure 1 A comparison chart of AST (IU / L) levels in mice;

[0026] Figure 2 A comparison chart of mouse ALT (IU / L);

[0027] Figure 3 A comparison chart of BUN (IU / L) levels in mice;

[0028] Figure 4 This is a comparison chart of UA (IU / L) in mice. Detailed Implementation

[0029] The technical solutions in the embodiments of the present invention will be clearly and completely described below. 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.

[0030] Pharmacological analysis:

[0031] Principal ingredient: Tripterygium wilfordii

[0032] Tripterygium wilfordii is bitter and cold in nature, and enters the liver, kidney, and heart meridians. In traditional Chinese medicine theory, its cold nature gives it the effects of clearing heat and detoxifying, removing dampness and relieving pain, especially in the treatment of rheumatism and various inflammatory diseases.

[0033] Traditional Chinese medicine believes that Tripterygium wilfordii has the effects of dispelling wind and dampness, strengthening muscles and bones, and clearing heat and detoxifying. It is often used to treat diseases such as rheumatoid arthritis, chronic nephritis, and systemic lupus erythematosus. Its main mechanism of action is to inhibit the immune system, reduce the activity of inflammatory cells, and reduce the release of cytokines, thereby achieving anti-inflammatory and anti-autoimmune effects.

[0034] Recent modern medical research has revealed various pharmacological effects of Tripterygium wilfordii, including its anti-inflammatory, immunomodulatory, and anti-tumor effects. The main active components of Tripterygium wilfordii, such as triptolide and triptolide, have shown protective effects in various kidney disease models, particularly in reducing proteinuria and improving renal function in diabetic nephropathy and nephrotic syndrome. However, the application of Tripterygium wilfordii is also limited by its potential nephrotoxicity and other organ toxicities.

[0035] The dual mechanism of action of Tripterygium wilfordii—exhibiting both therapeutic and toxic effects—has become a focus of modern research. Through ongoing in-depth mechanistic studies, researchers hope to find effective methods to reduce its toxicity while preserving its efficacy for better clinical application.

[0036] Assistant herb: Astragalus

[0037] Properties and Channels Entered: Sweet, slightly warm. Enters the spleen and lung channels.

[0038] Efficacy: Tonifies Qi and raises Yang, strengthens Wei Qi and consolidates the exterior, promotes tissue regeneration and detoxification, and promotes diuresis and reduces swelling.

[0039] Modern pharmacological effects: Flavonoids and polysaccharides are the main active ingredients in Astragalus membranaceus. These components have significant antioxidant effects, can scavenge free radicals, and protect cells from oxidative stress damage; the active ingredients in Astragalus membranaceus can significantly reduce inflammatory responses by inhibiting the release of inflammatory cytokines, thereby reducing tissue damage and inflammation; Astragalus membranaceus can modulate the immune system response, enhance the activity of immune cells such as macrophages and lymphocytes, and improve the body's immune defense capabilities.

[0040] Assistant herb: Sanguisorba officinalis

[0041] Properties and Channels Entered: Bitter, sour, slightly cold. Enters the Liver, Triple Energizer, and Large Intestine channels.

[0042] Efficacy: Cools the blood and stops bleeding, detoxifies and promotes wound healing.

[0043] Modern pharmacology: Sanguisorba officinalis contains a large amount of tannins, which have been proven to possess powerful anti-inflammatory and antioxidant properties. Tannins can help reduce inflammatory responses in the body, prevent and repair tissue damage, thus aiding in the treatment of various diseases caused by inflammation. Tannins not only help reduce inflammation but also accelerate the repair process of damaged tissues. This makes Sanguisorba officinalis particularly important in treating conditions requiring rapid recovery, such as enteritis or skin lesions. The antioxidant effects of Sanguisorba officinalis help eliminate free radicals in the body, protecting cells from oxidative stress damage, thereby maintaining normal cell function and structure.

[0044] The main ingredient: Ligustrum lucidum

[0045] Properties and Channels Entered: Sweet, bitter, cool. Enters the Liver and Kidney channels.

[0046] Efficacy: Nourishes the liver and kidneys, clears heat and improves eyesight.

[0047] Modern pharmacology: Modern research shows that privet fruit contains a variety of bioactive components, including flavonoids, saponins, and polysaccharides. These components work synergistically to provide its multifaceted pharmacological effects; the antioxidants in privet fruit can slow down the cellular aging process and prevent free radical damage to cells, thus delaying aging and improving vitality; flavonoids and saponins have significant anti-inflammatory effects, reducing the production and release of inflammatory mediators, and are used to treat various inflammatory diseases, such as arthritis and certain autoimmune diseases; privet fruit can also protect the liver and kidneys from damage caused by various toxins and pathological conditions, improving the functional state of these organs, especially showing good adjuvant therapeutic effects in the treatment of liver and kidney dysfunction.

[0048] Herbal ingredient: Eclipta prostrata

[0049] Properties and Channels Entered: Sweet and sour in taste, neutral in nature, and non-toxic. Enters the Kidney channel.

[0050] Efficacy: Nourishes Yin and benefits the kidneys, cools the blood and stops bleeding.

[0051] Modern pharmacological effects: Eclipta prostrata contains various bioactive components, such as cuneus-like compounds, which have been found to protect the liver from damage by chemical toxins and drugs through antioxidant effects and regulation of the body's enzyme system; the anti-inflammatory effect of Eclipta prostrata is mainly achieved by reducing the production and release of inflammatory mediators, such as reducing the production of prostaglandins and leukocytes, making it very effective in treating various inflammatory diseases; treatment of liver diseases and other inflammatory diseases: Eclipta prostrata extracts have been used to treat a variety of liver diseases, including hepatitis and cirrhosis, as well as other inflammatory diseases such as arthritis.

[0052] The four auxiliary herbs in the compound Tripterygium wilfordii preparation—Astragalus membranaceus, Sanguisorba officinalis, Ligustrum lucidum, and Eclipta prostrata—enhance the efficacy of the prescription through interaction and synergy, and effectively reduce the side effects of the main herb, Tripterygium wilfordii. This combination of herbs follows the principles of traditional Chinese medicine, achieving the effects of tonifying deficiency, clearing heat, detoxifying, and protecting the internal organs. Astragalus membranaceus, as a key herb for tonifying Qi, primarily functions to replenish Qi, promote pus drainage, and reduce swelling. In this formula, Astragalus membranaceus assists the anti-inflammatory and immunomodulatory effects of Tripterygium wilfordii by enhancing the body's immunity and promoting blood circulation, while simultaneously protecting liver and kidney function and reducing potential liver and kidney damage caused by Tripterygium wilfordii. Sanguisorba officinalis has the properties of clearing heat, cooling blood, and stopping bleeding, and is mainly used to treat bleeding problems caused by heat toxicity (such as hematochezia and hematuria). In this formula, Sanguisorba officinalis can alleviate the potential heat toxicity effects caused by Tripterygium wilfordii, especially providing protection and relief for microvascular damage or bleeding that may occur due to its strong efficacy. Privet fruit is renowned for its kidney-tonifying, liver-benefiting, vision-improving, and body-strengthening properties, primarily affecting the liver and kidney meridians. In compound formulas, privet fruit helps balance some of the side effects of Tripterygium wilfordii, such as its impact on the reproductive and endocrine systems. By replenishing liver and kidney yin, privet fruit can alleviate symptoms such as blurred vision, tinnitus, and seminal emission caused by liver and kidney yin deficiency, enhancing the overall harmonizing effect of the formula. Eclipta prostrata is widely used for its heat-clearing, detoxifying, liver-nourishing, and vision-improving effects. In this formula, eclipta prostrata strengthens the overall heat-clearing and detoxifying abilities, particularly in protecting liver function, helping to reduce the liver burden and inflammatory response that Tripterygium wilfordii may cause.

[0053] The combination of these four auxiliary herbs effectively assists the main function of Tripterygium wilfordii, making the entire compound more balanced, while providing effective relief and protection against potential side effects. By tonifying the liver and kidneys, enhancing immunity, cooling the blood and stopping bleeding, and clearing heat and detoxifying, these auxiliary herbs play a crucial role in the prescription, improving the safety and efficacy of treatment, making the compound more suitable for long-term and widespread clinical application.

[0054] Adjuvant: White-haired vine

[0055] Properties and Channels Entered: Bitter, slightly cold. Enters the Liver and Stomach channels.

[0056] Efficacy: Clears heat and detoxifies, promotes urination, and dispels wind and dampness.

[0057] Modern pharmacological effects: *Smilax glabra* contains abundant antioxidants, such as flavonoids and other polyphenols, which effectively scavenge free radicals and reduce oxidative stress, thus protecting body cells from damage. These antioxidants not only help reduce the risk of chronic diseases but also play an important role in anti-inflammatory effects, alleviating inflammation by inhibiting the activation of inflammatory cells and the production of inflammatory mediators. The antitumor activity of *Smilax glabra* is also a research hotspot. Its active ingredients have been found to inhibit the proliferation of certain types of cancer cells and induce apoptosis. Although these studies were mainly conducted under laboratory conditions, the results show that extracts of *Smilax glabra* have potential applications in the development of new anticancer therapies. *Smilax glabra* also exhibits good antibacterial and antiviral capabilities; its extracts can inhibit the growth of various pathogenic microorganisms, including bacteria and viruses. This broad antimicrobial activity makes *Smilax glabra* a potentially valuable resource for developing novel natural antibiotics and antiviral drugs. Studies have also found that *Smilax glabra* has a protective effect on the liver, especially in anti-hepatitis and hepatotoxicity. Its antioxidant components can alleviate liver damage caused by chemicals or drugs by reducing inflammatory responses and inhibiting oxidative stress, thus protecting hepatocytes.

[0058] Adjuvant: Schisandra chinensis

[0059] Properties and Channels Entered: Sour, warm. Enters the Lung, Kidney, and Heart channels.

[0060] Efficacy: It astringes the lungs and nourishes the kidneys, promotes the production of body fluids and stops sweating, astringes semen and stops diarrhea, and calms the mind and soothes the nerves.

[0061] Modern pharmacological effects: Studies show that Schisandra chinensis can enhance the body's immunity by increasing the activity of various immune cells, thereby strengthening the body's defense capabilities. The active ingredients in Schisandra chinensis have a protective effect on the liver, preventing and treating liver diseases such as hepatitis and liver fibrosis. This is mainly achieved by reducing inflammatory responses and inhibiting excessive hepatocyte death. Schisandra chinensis has a significant anti-fatigue effect, effectively prolonging working hours, reducing physical fatigue, and restoring physical strength. Schisandra chinensis is rich in antioxidants, such as vitamins C and E, which can scavenge free radicals in the body and protect cells from oxidative damage. Schisandra chinensis has a regulatory effect on the endocrine system, balancing hormone levels, especially playing a positive role in regulating stress hormones.

[0062] The role of adjuvant herbs is to assist the principal and assistant herbs in enhancing their efficacy, reducing or preventing potential side effects, and coordinating the overall potency of the prescription. In compound Tripterygium wilfordii preparations, the adjuvant herbs, *Tetrandria baicalensis* and *Schisandra chinensis*, fully embody this principle. Through their unique pharmacological activities, they synergistically work with other herbs to optimize the overall therapeutic effect. While Tripterygium wilfordii possesses good anti-inflammatory and immunosuppressive effects, long-term use may lead to the accumulation of heat toxins in the body, manifesting as symptoms such as dry mouth, fatigue, and constipation. The heat-clearing and dampness-draining effects of *Tetrandria baicalensis* can effectively reduce this heat toxin accumulation, thereby reducing these side effects. The hepatotoxicity of Tripterygium wilfordii is a significant limiting factor in its use. The heat-clearing and detoxifying functions of *Tetrandria baicalensis* help protect the liver and alleviate potential liver damage caused by Tripterygium wilfordii, especially when treating hepatitis or liver inflammation caused by Tripterygium wilfordii. *Schisandra chinensis* plays a crucial regulatory and balancing role. Its qi-tonifying, fluid-generating, kidney-tonifying, and heart-calming properties help alleviate potential immunosuppression, liver and kidney dysfunction, and nervous system-related side effects caused by Tripterygium wilfordii, thereby improving the overall safety and efficacy of the compound. In this way, Schisandra chinensis not only enhances the overall therapeutic effect but also helps reduce potential adverse reactions, making the treatment gentler and more protective.

[0063] Medicinal herb: Licorice

[0064] Properties and Channels Entered: Sweet, neutral. Enters the Heart, Lung, Spleen, and Stomach channels.

[0065] Efficacy: Tonifies the spleen and replenishes qi, moistens the lungs and relieves cough, relieves spasms and pain, and moderates the effects of other medicines.

[0066] Modern pharmacological effects: Licorice contains glycyrrhizic acid and glycyrrhetinic acid, which are effective in relieving and treating inflammatory conditions such as arthritis and dermatitis; antiviral activity: Licorice has been shown to have the ability to fight certain viruses, such as treating the common cold and influenza viruses; Licorice has a protective effect on the liver, and can help treat hepatitis and reduce the toxic damage of drugs to the liver.

[0067] In compound Tripterygium wilfordii preparations, licorice, as an adjuvant, not only enhances efficacy and detoxifies, but also helps balance and regulate the overall properties of the formula. By moderating the warming or cooling properties of other herbs, licorice ensures that the drugs in the formula can act more harmoniously on the body, reducing adverse reactions and enhancing therapeutic effects.

[0068] Example 1

[0069] A compound Tripterygium wilfordii composition, by weight, consists of the following medicinal materials:

[0070] Tripterygium wilfordii 10 parts, Astragalus membranaceus 20 parts, Sanguisorba officinalis 20 parts, Ligustrum lucidum 10 parts, Eclipta prostrata 10 parts, Aristolochia debilis 20 parts, Schisandra chinensis 5 parts, Glycyrrhiza uralensis 5 parts.

[0071] The medicinal materials mentioned are prepared slices of traditional Chinese medicine.

[0072] The preparation method of the above-mentioned compound Tripterygium wilfordii composition is characterized by comprising the following steps:

[0073] 1) Raw material processing: Wash all kinds of medicinal materials, remove impurities, crush them, dry them overnight, weigh them according to the weight parts in the formula and mix them to obtain mixture A;

[0074] (2) Decoction: Add mixture A to 10-20 times its weight of water, soak at 80-90℃ for 2-4 hours, then boil and reflux for 1-2 hours, filter to obtain the medicinal liquid and the residue, add 3-6 times its weight of water to the residue, heat and reflux for 30-60 minutes, combine the filtered medicinal liquid with the medicinal liquid obtained from the first filtration to obtain mixture B;

[0075] (3) Concentration and extraction: Mixture B was concentrated under reduced pressure at -0.07 to -0.08 MPa and 70 to 90°C until the density was 1.1 to 1.2 g / cm³. 3 Mixture C is obtained;

[0076] (4) Vacuum spray drying: The above mixture C is placed in a vacuum spray dryer for vacuum spray drying to obtain mixture D with a moisture content of less than 10%.

[0077] (5) Pre-freezing: Spread the above mixture D out to a thickness of 3-6cm, and perform rapid pre-freezing under normal pressure for 70-90min at a temperature of -30 to -50℃ to obtain mixture E.

[0078] (6) Freeze-drying: Under the condition of maintaining the pre-freezing temperature, add 5-10% by mass of glycerol as a freeze-drying protectant, mix thoroughly with mixture E, and then put it into a freeze dryer for freeze-drying. The freeze-drying procedure is as follows:

[0079] A: -45~-55℃, pressure 500-700Pa, freeze-dry for 45-75min;

[0080] B: -65~-55℃, pressure 120-220Pa, freeze-drying 120-240min;

[0081] C: -75~-85℃, pressure 60-120Pa, freeze-dry for 20-40min;

[0082] D: Return to normal temperature and pressure, dry until the moisture content is less than 5%, to obtain mixture F, which is the compound Tripterygium wilfordii composition.

[0083] Example 2

[0084] A compound Tripterygium wilfordii composition, by weight, consists of the following medicinal materials:

[0085] Tripterygium wilfordii 15 parts, Astragalus membranaceus 30 parts, Sanguisorba officinalis 30 parts, Ligustrum lucidum 15 parts, Eclipta prostrata 15 parts, Aristolochia debilis 30 parts, Schisandra chinensis 10 parts, Glycyrrhiza uralensis 10 parts.

[0086] The medicinal materials mentioned are prepared slices of traditional Chinese medicine.

[0087] The preparation method of the above-mentioned compound Tripterygium wilfordii composition is characterized by comprising the following steps:

[0088] 1) Raw material processing: Wash all kinds of medicinal materials, remove impurities, crush them, dry them overnight, weigh them according to the weight parts in the formula and mix them to obtain mixture A;

[0089] (2) Decoction: Add mixture A to 10-20 times its weight of water, soak at 80-90℃ for 2-4 hours, then boil and reflux for 1-2 hours, filter to obtain the medicinal liquid and the residue, add 3-6 times its weight of water to the residue, heat and reflux for 30-60 minutes, combine the filtered medicinal liquid with the medicinal liquid obtained from the first filtration to obtain mixture B;

[0090] (3) Concentration and extraction: Mixture B was concentrated under reduced pressure at -0.07 to -0.08 MPa and 70 to 90°C until the density was 1.1 to 1.2 g / cm³. 3 Mixture C is obtained;

[0091] (4) Vacuum spray drying: The above mixture C is placed in a vacuum spray dryer for vacuum spray drying to obtain mixture D with a moisture content of less than 10%.

[0092] (5) Pre-freezing: Spread the above mixture D out to a thickness of 3-6cm, and perform rapid pre-freezing under normal pressure for 70-90min at a temperature of -30 to -50℃ to obtain mixture E.

[0093] (6) Freeze-drying: Under the condition of maintaining the pre-freezing temperature, add 5-10% by mass of glycerol as a freeze-drying protectant, mix thoroughly with mixture E, and then put it into a freeze dryer for freeze-drying. The freeze-drying procedure is as follows:

[0094] A: -45~-55℃, pressure 500-700Pa, freeze-dry for 45-75min;

[0095] B: -65~-55℃, pressure 120-220Pa, freeze-drying 120-240min;

[0096] C: -75~-85℃, pressure 60-120Pa, freeze-dry for 20-40min;

[0097] D: Return to normal temperature and pressure, dry until the moisture content is less than 5%, to obtain mixture F, which is the compound Tripterygium wilfordii composition.

[0098] Example 3

[0099] A compound Tripterygium wilfordii composition, by weight, consists of the following medicinal materials:

[0100] Tripterygium wilfordii 20 parts, Astragalus membranaceus 20 parts, Sanguisorba officinalis 20 parts, Ligustrum lucidum 10 parts, Eclipta prostrata 10 parts, Lepidium apetalum 20 parts, Schisandra chinensis 5 parts, Glycyrrhiza uralensis 5 parts.

[0101] The medicinal materials mentioned are prepared slices of traditional Chinese medicine.

[0102] The preparation method of the above-mentioned compound Tripterygium wilfordii composition is characterized by comprising the following steps:

[0103] 1) Raw material processing: Wash all kinds of medicinal materials, remove impurities, crush them, dry them overnight, weigh them according to the weight parts in the formula and mix them to obtain mixture A;

[0104] (2) Decoction: Add mixture A to 10-20 times its weight of water, soak at 80-90℃ for 2-4 hours, then boil and reflux for 1-2 hours, filter to obtain the medicinal liquid and the residue, add 3-6 times its weight of water to the residue, heat and reflux for 30-60 minutes, combine the filtered medicinal liquid with the medicinal liquid obtained from the first filtration to obtain mixture B;

[0105] (3) Concentration and extraction: Mixture B was concentrated under reduced pressure at -0.07 to -0.08 MPa and 70 to 90°C until the density was 1.1 to 1.2 g / cm³. 3 Mixture C is obtained;

[0106] (4) Vacuum spray drying: The above mixture C is placed in a vacuum spray dryer for vacuum spray drying to obtain mixture D with a moisture content of less than 10%.

[0107] (5) Pre-freezing: Spread the above mixture D out to a thickness of 3-6cm, and perform rapid pre-freezing under normal pressure for 70-90min at a temperature of -30 to -50℃ to obtain mixture E.

[0108] (6) Freeze-drying: Under the condition of maintaining the pre-freezing temperature, add 5-10% by mass of glycerol as a freeze-drying protectant, mix thoroughly with mixture E, and then put it into a freeze dryer for freeze-drying. The freeze-drying procedure is as follows:

[0109] A: -45~-55℃, pressure 500-700Pa, freeze-dry for 45-75min;

[0110] B: -65~-55℃, pressure 120-220Pa, freeze-drying 120-240min;

[0111] C: -75~-85℃, pressure 60-120Pa, freeze-dry for 20-40min;

[0112] D: Return to normal temperature and pressure, dry until the moisture content is less than 5%, to obtain mixture F, which is the compound Tripterygium wilfordii composition.

[0113] Comparative Example 1

[0114] A compound Tripterygium wilfordii composition, by weight, consists of the following medicinal materials:

[0115] Tripterygium wilfordii 15 parts, Cyperus rotundus 30 parts, Schisandra chinensis 10 parts, Glycyrrhiza uralensis 10 parts.

[0116] The formula does not include 30 parts of Astragalus membranaceus, 30 parts of Sanguisorba officinalis, 15 parts of Ligustrum lucidum, or 15 parts of Eclipta prostrata; the rest is the same as in Example 2.

[0117] Comparative Example 2

[0118] A compound Tripterygium wilfordii composition, by weight, consists of the following medicinal materials:

[0119] Tripterygium wilfordii 15 parts, Eclipta prostrata 15 parts, Leonurus japonicus 30 parts, Schisandra chinensis 10 parts, Glycyrrhiza uralensis 10 parts.

[0120] Excluding 30 parts of Astragalus membranaceus, 30 parts of Sanguisorba officinalis, and 15 parts of Ligustrum lucidum, the rest are the same as in Example 2.

[0121] Comparative Example 3

[0122] A compound Tripterygium wilfordii composition, by weight, consists of the following medicinal materials:

[0123] Tripterygium wilfordii 15 parts, Ligustrum lucidum 15 parts, Eclipta prostrata 15 parts, Aristolochia debilis 30 parts, Schisandra chinensis 10 parts, Glycyrrhiza uralensis 10 parts.

[0124] Excluding 30 parts of Astragalus membranaceus and 30 parts of Sanguisorba officinalis, the rest are the same as in Example 2.

[0125] Comparative Example 4

[0126] A compound Tripterygium wilfordii composition, by weight, consists of the following medicinal materials:

[0127] Tripterygium wilfordii 15 parts, Sanguisorba officinalis 30 parts, Ligustrum lucidum 15 parts, Eclipta prostrata 15 parts, Aristolochia debilis 30 parts, Schisandra chinensis 10 parts, Glycyrrhiza uralensis 10 parts.

[0128] Excluding 30 portions of Astragalus membranaceus, the rest are the same as in Example 2.

[0129] Preparation Example 1

[0130] The compositions of Examples 1-3 and Comparative Examples 1-4 were prepared into compound Tripterygium wilfordii oral liquid. The freeze-dried compound Tripterygium wilfordii composition was dissolved in water to prepare a 2.5 wt% aqueous solution.

[0131] Preparation Example 2

[0132] The compositions of Examples 1-3 and Comparative Examples 1-4 were prepared into compound Tripterygium wilfordii oral liquid. The freeze-dried compound Tripterygium wilfordii composition was dissolved in water to prepare a 2.5 wt% aqueous solution. The oral liquid contained excipients, namely astaxanthin 0.2-0.5 wt%, tremella polysaccharide 2-3 wt%, glucose 5-10 wt%, and honey 5-10 wt%. The reason for adding the above excipients is to improve the taste and increase the stability and shelf life of the aqueous solution. Its active ingredients are the same as those in the preparation examples. In subsequent tests, the dosage form of Preparation Example 1 was used for testing.

[0133] Test Example 1

[0134] Experiments were conducted using the compound Tripterygium wilfordii oral liquid prepared according to Preparation Example 1 (Example 2) and Comparative Examples 1-4 to verify whether the compound Tripterygium wilfordii oral liquid prepared according to the present invention has fewer side effects.

[0135] 1. Experimental animals: 80 healthy female ICR mice (SPF), weighing approximately 25g.

[0136] Methods: Animal grouping and administration: Eighty female mice were randomly divided into eight groups of ten each: a control group and an experimental group (Examples 1-3 and Comparative Examples 1-4). There was no statistically significant difference in body weight among the groups (P > 0.05). The experimental group was administered 1 mL of compound Tripterygium wilfordii oral liquid by gavage daily, while the control group received the same volume of physiological saline. Stool characteristics, activity, and body weight changes were observed daily. After 30 days, the average body weight and liver and kidney function of each group were recorded. The following parameters were also measured: aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and uric acid (UA). The experimental and control groups were compared. Results are shown in Table 1 and... Figure 1-4 As shown.

[0137] Table 1. Liver and kidney function in mice

[0138] Blank group 152.31 35.3 5.32 41.3 Example 2 168.28 48.12 5.72 38.21 Comparative Example 1 298.20 147.12 8.21 57.21 Comparative Example 2 265.21 135.17 7.87 56.32 Comparative Example 3 245.42 128.31 7.35 52.12 Comparative Example 4 184.11 79.43 6.11 45.43

[0139] As can be seen from the data in Table 1 above, the present invention has found that the combination of Astragalus membranaceus, Sanguisorba officinalis, Ligustrum lucidum and Eclipta prostrata can effectively reduce the side effects of damage to liver and kidney function caused by Tripterygium wilfordii alone.

[0140] Test Example 2

[0141] A comparative experiment was conducted on the compound Tripterygium wilfordii oral liquid of Example 2 and Comparative Examples 1 and 4 to verify whether the compound Tripterygium wilfordii oral liquid of the present invention has a better therapeutic effect on chronic glomerulonephritis.

[0142] Eighty SD rats, weighing 150±10g (half male and half female), were acclimatized for 5 days. Ten rats were randomly selected and injected with 7.5mg / kg of physiological saline via tail vein as the normal control group. The remaining 70 rats were injected with 7.5mg / kg of doxorubicin hydrochloride via tail vein as the model group. After one week of normal feeding, the rats were placed in metabolic cages, and 24-hour urine was collected. The 24-hour urinary protein content was measured using the tungstic acid method. Rats with 24-hour urinary protein greater than 10mg were randomly divided into four groups of 10 rats each: the model group, Example 2 group, Comparative Example 1 group, and Comparative Example 4 group. All rats were fed normally until the end of the experiment. Example 2 group, Comparative Example 1 group, and Comparative Example 4 group were administered the corresponding drugs by gavage at a volume of 2mL once a day for 21 consecutive days. The 24-hour urinary protein content of the rats was measured again on days 7, 14, and 21 after administration. The specific results are shown in Table 2.

[0143] Table 2: 24-hour urinary protein in rats

[0144]

[0145] As can be seen from the data in Table 2, this invention has found that the combination of Astragalus membranaceus, Sanguisorba officinalis, Ligustrum lucidum, and Eclipta prostrata can effectively improve the therapeutic effect of Tripterygium wilfordii as a single drug for chronic glomerulonephritis.

[0146] As can be seen from the above embodiments and test examples, the present invention has found that the combination of Astragalus membranaceus, Sanguisorba officinalis, Ligustrum lucidum, and Eclipta prostrata can effectively reduce the side effects caused by Tripterygium wilfordii alone and improve the therapeutic effect of Tripterygium wilfordii. The oral liquid prepared by the above compound composition effectively improves the therapeutic effect of chronic glomerulonephritis and significantly reduces the side effects of Tripterygium wilfordii. It is suitable for patients with chronic kidney disease who need long-term treatment, helping them improve symptoms, improve quality of life, and reduce the risks caused by drug side effects.

[0147] The above are merely a few preferred embodiments of the present invention, described in a relatively specific and detailed manner, but they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A compound Tripterygium wilfordii composition for treating chronic glomerulonephritis, characterized in that, Made from the following medicinal materials by weight: Tripterygium wilfordii 10-20 parts, Astragalus membranaceus 20-40 parts, Sanguisorba officinalis 20-40 parts, Ligustrum lucidum 10-20 parts, Eclipta prostrata 10-20 parts, Aristolochia debilis 20-40 parts, Schisandra chinensis 5-15 parts, Glycyrrhiza uralensis 5-15 parts.

2. The compound Tripterygium wilfordii composition according to claim 1, characterized in that, Made from the following medicinal materials by weight: Tripterygium wilfordii 15 parts, Astragalus membranaceus 30 parts, Sanguisorba officinalis 30 parts, Ligustrum lucidum 15 parts, Eclipta prostrata 15 parts, Achyranthes bidentata 30 parts, Schisandra chinensis 10 parts, Glycyrrhiza uralensis 10 parts.

3. The compound Tripterygium wilfordii composition according to claim 1, characterized in that, The medicinal materials mentioned are prepared slices of traditional Chinese medicine.

4. The method for preparing the compound Tripterygium wilfordii composition according to any one of claims 1-3, characterized in that, Includes the following steps: 1) Raw material processing: Wash all kinds of medicinal materials, remove impurities, crush them, dry them overnight, weigh them according to the weight parts in the formula and mix them to obtain mixture A; (2) Decoction: Add mixture A to 10-20 times its weight of water, soak at 80-90℃ for 2-4 hours, then boil and reflux for 1-2 hours, filter to obtain the medicinal liquid and the residue. Add 3-6 times its weight of water to the residue, heat and reflux for 30-60 minutes, and combine the filtered medicinal liquid with the medicinal liquid obtained from the first filtration to obtain mixture B. (3) Concentration and extraction: Mixture B was concentrated under reduced pressure at -0.07 to -0.08 MPa and 70 to 90°C until the density was 1.1 to 1.2 g / cm³. 3 Mixture C is obtained; (4) Vacuum spray drying: The above mixture C is placed in a vacuum spray dryer for vacuum spray drying to obtain mixture D with a moisture content of less than 10%. (5) Pre-freezing: Spread the above mixture D out to a thickness of 3-6cm, and perform rapid pre-freezing under normal pressure for 70-90min at a temperature of -30~-50℃ to obtain mixture E; (6) Freeze-drying: Under the condition of maintaining the pre-freezing temperature, add 5-10% by mass of freeze-drying protectant, mix thoroughly with mixture E, and then put it into a freeze dryer for freeze-drying. The freeze-drying procedure is as follows: A: -45~-55℃, pressure 500-700Pa, freeze-dry for 45-75min; B: -65~-55℃, pressure 120-220Pa, freeze-drying 120-240min; C: -75~-85℃, pressure 60-120Pa, freeze-dry for 20-40min; D: Return to normal temperature and pressure, dry until the moisture content is less than 5%, to obtain mixture F, which is the compound Tripterygium wilfordii composition.

5. Use of the compound Tripterygium wilfordii composition according to any one of claims 1-3 in the preparation of a medicament for treating chronic glomerulonephritis.

6. A compound Tripterygium wilfordii oral liquid for treating chronic glomerulonephritis, characterized in that, Made from the compound Tripterygium wilfordii composition according to any one of claims 1-3.

7. The compound Tripterygium wilfordii oral liquid according to claim 6, characterized in that, The oral liquid is prepared by adding ultrapure water and oral liquid excipients to a compound Tripterygium wilfordii composition as the active ingredient.

8. The compound Tripterygium wilfordii oral liquid according to claim 7, characterized in that, The compound Tripterygium wilfordii composition contains 2-5 wt%, and the excipients for the oral liquid are astaxanthin 0.2-0.5 wt%, Tremella fuciformis polysaccharide 2-3 wt%, glucose 5-10 wt%, honey 5-10 wt%, and the balance is water.

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