Traditional Chinese medicine composition for treating hyperuricemia, preparation method and application thereof

Abstract

This invention discloses a traditional Chinese medicine composition for treating hyperuricemia of the spleen and kidney deficiency with turbidity syndrome, its preparation method, and its application, belonging to the field of pharmaceutical technology. The composition consists of Euryale ferox, Rosa laevigata, Plantago asiatica, Alisma plantago-aquatica, Cimicifuga foetida, Smilax glabra, and Portulaca oleracea in specific weight proportions. The active ingredients are prepared using a combination of ethanol reflux extraction and water extraction, and can be further formulated into capsules, pills, granules, tablets, and other traditional Chinese medicine preparations. This invention has high safety, few side effects, and good patient compliance, making it suitable for long-term intervention and providing a new approach for the treatment of hyperuricemia with traditional Chinese medicine.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a traditional Chinese medicine composition for treating hyperuricemia, its preparation method, and its application. Background Technology

[0002] Hyperuricemia (HUA) is a metabolic disease caused by purine metabolism disorders, leading to excessive uric acid production or reduced excretion in the blood, resulting in serum uric acid levels exceeding 420 μmol / L. Over the past decade, hyperuricemia has rapidly evolved from a traditionally perceived "disease of affluence" into one of the most common metabolic diseases, with a significant increase in global prevalence. The latest epidemiological survey data shows that the total number of HUA patients worldwide exceeded 1.1 billion in 2020 and is projected to reach 1.42 billion by 2030, affecting 8-25% of the population. Furthermore, the prevalence is increasing annually and showing a trend towards affecting younger individuals.

[0003] Hyperuricemia coexists with multiple chronic diseases and has become an independent risk factor for cardiovascular disease, chronic kidney disease, and various metabolic diseases, as well as an independent predictor of premature death, posing a serious global public health challenge. Current treatment strategies for lowering uric acid mainly include: inhibiting uric acid synthesis (such as allopurinol and febuxostat), using recombinant uricase (such as raburicase), promoting uric acid excretion (such as probenecid and benzbromarone), and injecting uricase (such as polyethylene glycol recombinant uricase).

[0004] While the aforementioned medications can lower uric acid levels to some extent, they suffer from significant side effects, numerous adverse reactions, and contraindications. Specifically, allopurinol can trigger fatal allergic reactions; febuxostat poses cardiovascular risks; recombinant uricase can cause rapid allergic reactions; and benzbromarone can induce delayed-type liver and kidney damage. Furthermore, the symptoms of hyperuricemia are often insidious, and due to the combined effects of these factors, patient compliance is only 36.8%, with rebound effects after discontinuation, limiting their clinical application. Therefore, there is an urgent need to find a safer and more effective treatment method to intervene in the progression of hyperuricemia.

[0005] Traditional Chinese medicine (TCM) treatment of hyperuricemia can intervene in the early stages of the disease, has fewer side effects, is suitable for a wider range of people, and has many advantages. Because TCM is characterized by syndrome differentiation and treatment, fewer side effects, and lower cost, research on TCM treatment of hyperuricemia has gradually gained attention in recent years, and its efficacy has shown many superior results. Summary of the Invention

[0006] In view of the clinical limitations of existing drugs for the treatment of hyperuricemia, such as large side effects, poor patient compliance, and easy rebound after drug withdrawal, this invention provides a traditional Chinese medicine composition for the treatment of hyperuricemia with definite efficacy, high safety, and good patient compliance, as well as its preparation method and application.

[0007] This invention is based on the understanding of the pathogenesis of hyperuricemia in Traditional Chinese Medicine (TCM): TCM believes that "the spleen nourishes the four limbs, and the kidneys nourish the hundred bones. Food and water enter the stomach, are transformed into essence, and transported to the spleen; the clear is called essence, like rain and dew; the impure is called turbidity, like sewage. Therefore, essence returns to the five viscera, is stored in the kidneys, and nourishes the hundred bones; water returns to the bladder, and the kidneys act as its gate, expelling turbidity and cleansing the body. Essence and turbidity each follow their own path; when insufficient, they are nourished; when excessive, they are expelled. A healthy body and full form mean freedom from disease." Improper diet, imbalance of hot and cold, and consumption of rich and fatty foods damage the spleen and stomach, leading to spleen dysfunction. Firstly, the generation of acquired essence is insufficient, resulting in deficiency of essence in the five viscera, inability of the kidneys to store essence, and malnourishment of the hundred bones. Secondly, dampness and turbidity overflow, hindering the kidneys' function and allowing turbidity to spread. The nature of turbidity is superficially related to earth and fundamentally related to water; they follow the same principle, and their primary pathogenic factor is the bone and kidneys. This disease is only applicable to the syndrome of spleen and kidney deficiency with turbidity. The treatment should focus on tonifying the spleen and kidney, consolidating essence and eliminating turbidity, so that essence and turbidity can each follow their own path, turbidity can be eliminated and cleansed, essence can return to the internal organs, and the whole body can be nourished.

[0008] Based on the above theory, the present invention provides a traditional Chinese medicine composition for treating hyperuricemia of the spleen and kidney deficiency with turbidity syndrome. The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 2-4 parts of Euryale ferox, 2-4 parts of Rosa laevigata, 2-4 parts of Plantago asiatica, 1-3 parts of Alisma plantago-aquatica, 0.5-1.5 parts of Cimicifuga foetida, 3-5 parts of Smilax glabra, and 1-3 parts of Portulaca oleracea.

[0009] Preferably, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 3 parts Euryale ferox, 3 parts Rosa laevigata, 3 parts Plantago asiatica, 2 parts Alisma plantago-aquatica, 1 part Cimicifuga foetida, 4 parts Smilax glabra, and 2 parts Portulaca oleracea.

[0010] Furthermore, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine composition, comprising the following steps:

[0011] (1) Take Euryale ferox, Rosa laevigata, Plantago asiatica, Alisma plantago-aquatica, Cimicifuga foetida, Smilax glabra and Portulaca oleracea, mix them evenly to obtain a mixture of raw materials;

[0012] (2) Add 6-10 times the total weight of the raw materials to the mixture of raw materials and ethanol with a mass concentration of 60-70%, heat and reflux for 1-2 hours, filter, and obtain the first filtrate;

[0013] (3) The first filtrate is depressurized to recover ethanol and concentrated to 1 / 2-1 / 3 of its original volume to prepare solution A;

[0014] (4) Take the dregs filtered in step (2), add 5-7 times the total weight of the raw materials of water, decoct twice, each time for 1-2 hours, combine the decoctions, filter, and obtain the second filtrate;

[0015] (5) The second filtrate is concentrated under reduced pressure to 1 / 2-1 / 3 of its original volume to prepare solution B;

[0016] (6) Mix liquid A and liquid B and concentrate them to a clear paste with a relative density of 1.15-1.30 at 45°C to obtain the active ingredient of the traditional Chinese medicine composition of the present invention.

[0017] Preferably, in step (2), ethanol with a mass concentration of 65% is added at 8 times the total weight of the raw material, and the mixture is heated and refluxed for 1.5 hours for extraction.

[0018] Preferably, in step (4), water equal to 6 times the total weight of the raw materials is added, and the mixture is decocted twice, each time for 1.5 hours.

[0019] Furthermore, the present invention provides a traditional Chinese medicine preparation made from the active ingredients of the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0020] The excipients are one or more of starch, dextrin, talc, magnesium stearate, and calcium sulfate.

[0021] The dosage form of the traditional Chinese medicine preparation is one of capsules, pills, granules or tablets.

[0022] Preferably, the traditional Chinese medicine preparation is a granule, and its preparation method is as follows: add 20-50% of the weight of excipients to the clear paste obtained in the above step (6), and prepare granules according to the conventional preparation method of granules.

[0023] Formulation principle The herbal composition of this invention uses the principle of tonifying the spleen and kidneys, consolidating essence and eliminating turbidity as its therapeutic approach, and is formulated according to the principles of monarch, minister, assistant, and guide in traditional Chinese medicine formulation.

[0024] The principal herbs are: Euryale ferox and Rosa laevigata. Euryale ferox is sweet and astringent, tonifying the spleen, strengthening the kidneys, and astringing essence; Rosa laevigata is sour and astringent, strengthening essence and reducing urination. The combination of these two herbs tonifies the spleen and kidneys and strengthens essence, with a focus on tonifying kidney deficiency to consolidate and retain essence.

[0025] Assistant herbs: Plantago seed, Alisma rhizome, and Smilax glabra rhizome. Plantago seed drains heat downwards and separates clear from turbid; Alisma rhizome promotes urination and eliminates turbidity, removing kidney turbidity; Smilax glabra rhizome detoxifies, removes dampness, and promotes joint mobility. The three herbs work together to promote urination, drain dampness, and eliminate turbidity, addressing the symptoms of internal dampness and turbidity retention, and assisting the principal herb in expelling pathogenic factors.

[0026] Adjuvant herbs: Purslane and Cimicifuga. Purslane clears heat and detoxifies, cools the blood and promotes diuresis, clears dampness and turbidity and prevents damp-heat stagnation; Cimicifuga lightly clears and lifts, regulates the Qi mechanism, and assists the clear Yang in rising among the diuretic herbs in the whole formula, so that the Qi mechanism can be regulated and the turbid Yin can be naturally descended, which helps to protect the body's vital energy and avoids excessive diuresis, reflecting the compatibility concept of "rising before descending".

[0027] The formula uses seven herbs together, which astringe and benefit the middle, tonify and consolidate, and treat both seminal and turbid substances separately, thus achieving the effects of tonifying the spleen and kidneys, consolidating essence and eliminating turbid substances.

[0028] Beneficial effects 1. Definite Efficacy: This invention targets patients with hyperuricemia due to spleen and kidney deficiency with turbidity syndrome. The clinical trial adopted a multicenter, randomized, double-blind, double-dummy, parallel-controlled design, with febuxostat as the first-line Western medicine as the control. The results showed that the serum uric acid in the experimental group decreased from 566.0±75.4μmol / L before treatment to 333.6±80.0μmol / L (P<0.05), with a total effective rate of 86%. Under the equivalent clinical design, the efficacy was better than that of the febuxostat control group (72%), and the uric acid-lowering effect was significant.

[0029] 2. High safety: The formula is made of pure traditional Chinese medicine, with no obvious toxic side effects. It can be taken for a long time, and patients have good compliance. It avoids problems such as allergies, liver and kidney damage, and cardiovascular risks associated with Western medicine.

[0030] 3. Scientific formulation: Based on the TCM principle of "tonifying the spleen and kidneys, consolidating essence and eliminating turbidity", it precisely targets the syndrome of spleen and kidney deficiency with turbidity. The combination of principal, assistant, adjuvant and guide herbs is rigorous. It intervenes in hyperuricemia from the perspective of treating essence and turbidity separately. The theory and clinical practice are closely integrated.

[0031] 4. Simple preparation process: The combination of alcohol extraction and water extraction ensures sufficient retention of components, is easy to operate, has low cost, and is suitable for industrial production.

[0032] 5. Broad application prospects: It can effectively reduce blood uric acid, prevent acute gouty arthritis and tophi, reduce dependence on Western medicine, and has both clinical value and socio-economic benefits. Detailed Implementation

[0033] Example 1: Granules of Traditional Chinese Medicine Composition

[0034] Prescription: 3 parts Euryale ferox, 3 parts Rosa laevigata, 3 parts Plantago asiatica, 2 parts Alisma plantago-aquatica, 1 part Cimicifuga foetida, 4 parts Smilax glabra, 2 parts Portulaca oleracea.

[0035] Preparation method:

[0036] (1) Take seven raw materials and mix them evenly to obtain a mixture of raw materials;

[0037] (2) Add 8 times the total weight of 65% ethanol, heat and reflux for 1.5 hours, and filter to obtain the first filtrate;

[0038] (3) The ethanol in the first filtrate was recovered under reduced pressure and concentrated to 1 / 2 of the original volume to obtain solution A;

[0039] (4) Add 6 times the total weight of water to the dregs and decoct twice, 1.5 hours each time. Combine the filtrates and concentrate to 1 / 2 of the original volume to obtain solution B.

[0040] (5) Mix solution A and solution B and concentrate to a clear paste with a relative density of 1.20 at 45℃;

[0041] (6) Add 30% of the weight of the extract excipients (starch: dextrin = 2:1), granulate and dry to obtain granules.

[0042] Example 2: Capsule Formulation of Traditional Chinese Medicine Composition

[0043] Prescription: 4 parts Euryale ferox, 4 parts Rosa laevigata, 2 parts Plantago asiatica, 3 parts Alisma plantago-aquatica, 1.5 parts Cimicifuga foetida, 5 parts Smilax glabra, and 3 parts Portulaca oleracea.

[0044] Preparation method:

[0045] (1) Mixed active pharmaceutical ingredients;

[0046] (2) Add 10 times the amount of 60% ethanol and reflux for 2 hours, then filter and concentrate to obtain solution A;

[0047] (3) Add 7 times the amount of water to the dregs and decoct twice, 2 hours each time, and concentrate to obtain solution B;

[0048] (4) Mix and concentrate to a relative density of 1.30, add 40% excipients to granulate and encapsulate.

[0049] Example 3: Traditional Chinese Medicine Composition Tablets

[0050] Prescription: 2 parts Euryale ferox, 2 parts Rosa laevigata, 4 parts Plantago asiatica, 1 part Alisma plantago-aquatica, 0.5 parts Cimicifuga foetida, 3 parts Smilax glabra, 1 part Portulaca oleracea.

[0051] Preparation method:

[0052] (1) Mixed active pharmaceutical ingredients;

[0053] (2) Add 6 times the amount of 70% ethanol and reflux for 1 hour, then filter and concentrate to obtain solution A;

[0054] (3) Add 5 times the amount of water to the dregs and decoct twice, 1 hour each time, and concentrate to obtain solution B;

[0055] (4) Mix and concentrate to a relative density of 1.15, add 20% excipients to granulate and compress tablets.

[0056] Example 4: Traditional Chinese Medicine Composition in Pill Formation

[0057] Prescription: 2.5 parts Euryale ferox, 3.5 parts Rosa laevigata, 2.5 parts Plantago asiatica, 1.5 parts Alisma plantago-aquatica, 0.8 parts Cimicifuga foetida, 3.5 parts Smilax glabra, and 1.5 parts Portulaca oleracea.

[0058] Preparation method:

[0059] (1) Mixed active pharmaceutical ingredients;

[0060] (2) Add 8 times the amount of 65% ethanol and reflux for 1.5 hours, then filter and concentrate to obtain solution A;

[0061] (3) Add 6 times the amount of water to the dregs and decoct twice, 1.5 hours each time, and concentrate to obtain solution B;

[0062] (4) Mix and concentrate to a relative density of 1.20 for a clear paste, add 30% excipients to make pills and dry.

[0063] Clinical trial introduction:

[0064] I. Research Methods

[0065] Research subjects:

[0066] Inclusion criteria: ① Meets the diagnostic criteria for hyperuricemia in the "Chinese Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout (2019 Edition)"; ② Has a TCM syndrome of spleen and kidney deficiency with turbidity; ③ Is aged 18-65 years; ④ Has signed an informed consent form.

[0067] Exclusion criteria: acute gout, tophi, severe liver or kidney dysfunction, malignant tumors, drug allergies, participation in other clinical trials within the past 3 months, pregnancy, lactation, etc.

[0068] Withdrawal / discontinuation criteria: intolerance to adverse reactions, non-compliance with medication use, violation of protocol, loss to follow-up, occurrence of serious safety issues, etc.

[0069] Research Design:

[0070] Multicenter, randomized, double-blind, double-dummy, parallel-controlled study; a total of 114 cases were included, with 57 cases in each group.

[0071] Experimental group: basic intervention + febuxostat mimic + the granules of this invention (15g / sachet, 3 times a day, taken before meals).

[0072] Control group: Basic intervention + febuxostat tablets (40mg, once daily) + traditional Chinese medicine analogue.

[0073] Treatment duration: 4 weeks.

[0074] Observation indicators:

[0075] Primary indicator: serum uric acid level; Secondary indicators: TCM syndrome score, overall effective rate; Safety indicators: routine blood and urine tests, liver and kidney function tests, etc.

[0076] II. Research Results

[0077] 1. Blood uric acid level:

[0078] Table 1 Comparison of serum uric acid levels before and after treatment in the two groups (x±s, μmol / L)

[0079] 2. Clinical efficacy:

[0080] Table 2 Comparison of clinical efficacy between the two groups of patients

[0081] 3. Security:

[0082] No significant adverse reactions were observed in either group, and liver and kidney function, blood routine tests, etc. were normal, indicating good safety.

[0083] The traditional Chinese medicine composition of this invention can specifically reduce the serum uric acid level in patients with hyperuricemia due to spleen and kidney deficiency with turbidity syndrome. It has a high overall clinical efficacy, good safety, good compliance, and is suitable for long-term intervention.

Claims

1. A traditional Chinese medicine composition for treating hyperuricemia, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: 2-4 parts of Euryale ferox, 2-4 parts of Rosa laevigata, 2-4 parts of Plantago asiatica, 1-3 parts of Alisma plantago-aquatica, 0.5-1.5 parts of Cimicifuga foetida, 3-5 parts of Smilax glabra, and 1-3 parts of Portulaca oleracea.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: 3 parts Euryale ferox, 3 parts Rosa laevigata, 3 parts Plantago asiatica, 2 parts Alisma plantago-aquatica, 1 part Cimicifuga foetida, 4 parts Smilax glabra, and 2 parts Portulaca oleracea.

3. A method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, Includes the following steps: (1) Take Euryale ferox, Rosa laevigata, Plantago asiatica, Alisma plantago-aquatica, Cimicifuga foetida, Smilax glabra and Portulaca oleracea, mix them evenly to obtain a mixture of raw materials; (2) Add ethanol solution to the mixture of raw materials, heat and reflux to extract, filter, and obtain the first filtrate; (3) The first filtrate is depressurized to recover ethanol, concentrated, and prepared into solution A; (4) Take the dregs filtered in step (2), add water and decoct, then filter to obtain the second filtrate; (5) The second filtrate is concentrated to prepare solution B; (6) Mix liquid A and liquid B and concentrate to a clear paste to obtain the active ingredients of the traditional Chinese medicine composition.

4. The preparation method according to claim 3, characterized in that, The ethanol solution in step (2) has a mass concentration of 60-70%, and the amount used is 6-10 times the total weight of the raw material. The heating and reflux extraction time is 1-2 hours.

5. The preparation method according to claim 3, characterized in that, The amount of water used in step (4) is 5-7 times the total weight of the raw materials. The decoction is performed twice, with each decoction lasting 1-2 hours.

6. The preparation method according to claim 3, characterized in that, The concentration described in step (3) is to concentrate to 1 / 2-1 / 3 of the original volume, and / or the concentration described in step (5) is to concentrate to 1 / 2-1 / 3 of the original volume, and / or the clear paste described in step (6) has a relative density of 1.15-1.30 at 45°C.

7. A traditional Chinese medicine preparation, characterized in that, The active ingredient of a traditional Chinese medicine composition prepared by the method described in any one of claims 1 or 2, or by any one of claims 3-6, is made by adding pharmaceutically acceptable excipients.

8. The traditional Chinese medicine preparation according to claim 7, characterized in that, The excipients are one or more of starch, dextrin, talc, magnesium stearate, and calcium sulfate.

9. The traditional Chinese medicine preparation according to claim 8, characterized in that, The dosage form of the traditional Chinese medicine preparation is one of capsules, pills, granules or tablets.

10. The use of the traditional Chinese medicine composition according to claim 1 or 2, the active ingredient of the traditional Chinese medicine composition prepared by the preparation method according to any one of claims 3-6, or the traditional Chinese medicine preparation according to any one of claims 7-9 in the preparation of drugs for hyperuricemia.

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