A Chinese medicine composition for preventing and / or treating refractory gout and preparation method thereof

Abstract

The present invention relates to a Chinese medicine composition for preventing and / or treating refractory gout, wherein the Chinese medicine raw materials of the Chinese medicine composition are composed of the following ingredients: raw astragalus, leech, Poria, raw white atractylodes, chuanxiong, zedoaria, atractylodes, raw coix seeds, smilax, radix polygoni multiflori, white peony root, chuanxiong, and raw liquorice. The present invention also provides a preparation method of the Chinese medicine composition. The Chinese medicine composition of the present invention is used to prevent and / or treat (1) joint swelling and pain, (2) subcutaneous nodules or dark purple skin, (3) recurrent attacks, symptoms that do not heal over time, or at least one of the following three symptoms caused by refractory gout: (1) using a sufficient amount of conventional uric acid-lowering drugs alone or in combination for a sufficient course of treatment, the blood uric acid level is still ≥360 μmol / L; (2) receiving standardized treatment, gout still attacks ≥2 times / year; (3) the presence of multiple and (or) progressive tophi. The Chinese medicine composition of the present invention has significant therapeutic effect on preventing and / or treating refractory gout, has reasonable formula, safe and reliable therapeutic effect and small side effects.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for preventing and / or treating refractory gout and a preparation method thereof. Background Art

[0002] Gouty arthritis is a crystal-related arthritis caused by the deposition of monosodium urate in joints when the uric acid in the blood exceeds its saturation in the blood or tissue fluid, inducing local inflammatory reactions and tissue destruction. It is directly related to hyperuricemia caused by purine metabolism disorders and / or reduced uric acid excretion, and is the second largest metabolic disease after diabetes. Refractory gout is a chronic, multiple, destructive arthritis with tophi formation and / or uric acid kidney stones that occurs after repeated attacks of acute gouty arthritis for several years, and conventional uric acid-lowering drugs are difficult to bring the blood uric acid level to the standard. With the continuous improvement of living standards, the prevalence of refractory gout has increased year by year and is gradually showing a trend of younger age. According to epidemiological statistics of the Chinese population, the prevalence of gout is as high as 1.1%, and refractory gout accounts for about 1% of the total number of gout patients. Many evidences show that refractory gout is more likely to have systemic complications, and the risk of end-stage renal disease, cardiovascular and cerebrovascular accidents and all-cause mortality will increase. The treatment of refractory gout to the standard and the prevention of acute relapses are the key points and difficulties in clinical practice.

[0003] The current treatment plan of Western medicine is: maintain a healthy lifestyle, including weight control and regular exercise; limit the intake of alcohol and high-purine, high-fructose diets; encourage the intake of dairy products and fresh vegetables; do not recommend or limit the intake of soy products (such as tofu); prevent strenuous exercise or sudden cold; quit smoking, drink plenty of water (>2000ml / 24h), and alkalize urine (maintain the pH value of morning urine at 6.2-6.9). Uric acid-lowering drugs include: drugs that inhibit uric acid production, such as allopurinol and febuxostat; drugs that promote uric acid excretion, such as benzbromarone and probenecid; anti-inflammatory and analgesic drugs, such as colchicine, non-steroidal anti-inflammatory drugs, and glucocorticoids. Traditional Chinese medicine generally believes that the nature of refractory gout is deficiency of the root and excess of the symptoms. The root deficiency includes the deficiency of qi, blood, yin and yang of the internal organs, and the excess of the symptoms includes various pathological products such as phlegm, blood stasis, damp heat, turbid toxins, etc. However, there is currently no relevant research using Chinese medicinal materials including raw astragalus, leech, Poria, raw Atractylodes, Ligusticum chuanxiong, Curcuma, Atractylodes, raw Coix seed, Smilax glabra, Radix Dianthus, white peony, Cyathula, and raw licorice. Summary of the invention

[0004] In view of this, the present invention provides a traditional Chinese medicine composition for preventing and / or treating refractory gout, wherein the Chinese medicinal materials of the traditional Chinese medicine composition are composed of the following ingredients: raw astragalus, leech, Poria, raw white atractylodes, ligusticum chuanxiong, curcuma, atractylodes, raw coix seed, smilax glabra, radix polygoni multiflori, white peony root, cyathula capitata, and raw licorice.

[0005] The raw astragalus, leech, Poria, raw white atractylodes, chuanxiong, zedoaria, atractylodes, raw coix seed, smilax, radix polygoni multiflori, white peony root, chuanxiong and raw licorice are directly purchased or prepared according to the legal processing methods of the Chinese Pharmacopoeia.

[0006] Further optionally, the Chinese medicinal materials are composed of the following weight ratios: 2-10 parts of raw astragalus, 0.2-1.5 parts of leech, 1-5 parts of Poria, 1-5 parts of raw Atractylodes, 1-5 parts of Ligusticum chuanxiong, 1-5 parts of Curcuma, 1-5 parts of Atractylodes, 1-6 parts of raw Coix seeds, 1-6 parts of Smilax glabra, 1-5 parts of Radix Dioscoreae, 1-6 parts of White Peony, 1-5 parts of Cyathula, and 0.3-5 parts of raw licorice.

[0007] Further optionally, the Chinese medicinal materials are composed of the following weight ratios: 3 parts of raw astragalus, 0.3 parts of leech, 1.5 parts of Poria, 1 part of raw Atractylodes, 1.5 parts of Ligusticum chuanxiong, 1 part of Curcuma, 1 part of Atractylodes, 3 parts of raw Coix seeds, 3 parts of Smilax glabra, 1 part of Radix Dioscoreae, 3 parts of White Peony, 1 part of Cyathula, and 0.9 parts of raw licorice.

[0008] The present invention provides a method for preparing the above-mentioned Chinese medicine composition, and the preparation method comprises the following steps:

[0009] Weigh various Chinese medicinal materials according to weight ratio and mix them;

[0010] Add water and boil several times, combining the decoctions from each time;

[0011] Filter and concentrate to obtain a concentrate.

[0012] Further optionally, the concentrated solution is prepared as a decoction.

[0013] Further optionally, the preparation method further comprises the following steps:

[0014] The concentrated liquid is further concentrated to a clear paste, auxiliary materials are added, and the dried material is granulated to obtain granules.

[0015] The present invention provides an application of the above-mentioned traditional Chinese medicine composition in preparing a medicine for preventing and / or treating refractory gout.

[0016] Further optionally, the symptoms of refractory gout are:

[0017] (1) Joint swelling and pain, (2) subcutaneous nodules or dark purple skin, (3) repeated attacks that do not heal over time; or at least one of the following three symptoms: (1) serum uric acid level is still ≥360 μmol / L despite adequate dosage and duration of conventional uric acid-lowering drugs alone or in combination; (2) gout attacks ≥2 times / year despite standardized treatment; (3) the presence of multiple and / or progressive tophi.

[0018] Based on many years of clinical experience in traditional Chinese medicine, the inventor has summarized the diagnosis and treatment rules and empirical medication for refractory gout. He believes that the pathogenesis of this disease is spleen deficiency, turbid blood stasis and numbness. Therefore, the treatment principle should be to strengthen the spleen, eliminate turbidity and resolve blood stasis, which runs through the entire process of treating refractory gout. In the formula, raw Astragalus membranaceus strengthens the spleen, replenishes the middle and reduces swelling, and leeches break blood, remove blood stasis and eliminate numbness. They are the main medicines, one qi and one blood, replenishing qi and activating blood circulation, and clearing dampness and numbness. Poria strengthens the spleen and eliminates dampness, and Atractylodes macrocephala strengthens the spleen and eliminates dampness. "Ben Jing Feng Yuan" says that "Astragalus membranaceus, Atractylodes macrocephala and Poria cocos can move spleen dampness." The two medicines help Astragalus membranaceus strengthen the spleen and eliminate dampness, while Chuanxiong activates blood circulation, promotes qi, eliminates numbness and relieves pain, and Curcuma zedoaria removes blood stasis and eliminates lumps. The two medicines help leeches to eliminate blood stasis and eliminate symptoms, and are both auxiliary medicines. Medicine; Atractylodes, Coix Seed, and Smilax glabra can both strengthen the spleen and eliminate dampness, and can enter the meridians to search for phlegm and dampness, and unclog the joints. Radix Dianthus can eliminate dampness, eliminate turbidity, eliminate numbness and relieve pain, and white peony root can relieve urgency and relieve pain, and they are all adjuvants; Cyathula officinalis can lead the medicine downward, promote blood circulation, tonify the kidney and strengthen the tendons, and liquorice harmonizes the various medicines, and they are all guiding medicines. The whole prescription is both attacking and tonifying, and can tonify the middle and promote unblocking. It can not only strengthen the spleen, but also eliminate turbidity, resolve blood stasis and eliminate numbness, and can achieve the effect of treating both the symptoms and the root cause.

[0019] The present invention obtains the active ingredients of the Chinese medicine prescription after decoction and extraction of the Chinese medicine, and after taking these extracts orally, refractory gout can be prevented and / or treated. According to common sense, those skilled in the art can understand that the present invention realizes the simplest implementation mode of preventing and / or treating refractory gout, which can be to directly take the concentrated decoction after decoction and extraction of the Chinese medicine. In order to alleviate the difficulty of taking medicine for patients, those skilled in the art can prepare other oral preparations by combining the clear paste extracted from the Chinese medicine with conventional adjuvants in the art according to conventional preparation technology, such as preparing granules. For example, the clear paste obtained by concentrating the present invention is prepared into granules, one dose per day, 400ml of water is taken, and it is taken warm twice a day after meals in the morning and evening, one month is one course of treatment, and three courses of treatment are used continuously.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The Chinese medicine composition of the present invention has significant therapeutic effect on preventing and / or treating refractory gout, has reasonable formula, safe and reliable therapeutic effect and small side effects. DETAILED DESCRIPTION

[0022] The following is a description of the implementation of the present invention by specific embodiments. People familiar with the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0023] The terms used in the embodiments of the present invention are only for the purpose of describing specific embodiments, and are not intended to limit the present invention. The singular forms "a", "said" and "the" used in the embodiments of the present invention and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings, and "multiple" generally includes at least two, but does not exclude the inclusion of at least one.

[0024] Examples 1-6

[0025] Weigh each Chinese medicinal material according to the weight shown in Table 1.

[0026] Table 1: Weight of each Chinese medicinal material in Examples 1-6

[0027]

[0028]

[0029] Example 7

[0030] Embodiment 7 is to prepare granules from the Chinese medicinal materials of embodiment 1, and the preparation method comprises the following steps:

[0031] Weigh 30g of raw astragalus, 3g of leech, 15g of Poria, 10g of raw Atractylodes, 15g of Chuanxiong, 10g of Curcuma, 10g of Atractylodes, 30g of raw Coix seeds, 30g of Smilax glabra, 10g of Radix Dioscoreae, 30g of White Peony Root, 10g of Cyathula, and 9g of raw Licorice respectively, mix them, add water and boil, combine the decoctions, filter, concentrate to a clear paste, add auxiliary materials, dry, add auxiliary materials again, mix well, and granulate to obtain the product.

[0032] Test example

[0033] This test example is a clinical study on the Chinese medicine composition granules prepared in Example 7 in the treatment of refractory gout.

[0034] Case selection: A total of 96 patients with refractory gout were randomly selected from Fangshan Hospital of Beijing University of Chinese Medicine. The baseline conditions were comparable and the diagnosis was based on the following criteria: Western medicine diagnostic criteria refer to the "2019 Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China": (1) Refractory gout, at least one of the following three conditions: ① The serum uric acid level is still ≥360 μmol / L after sufficient use of conventional uric acid-lowering drugs alone or in combination for a sufficient course of treatment; ② Gout attacks ≥2 times / year despite standardized treatment; ③ The presence of multiple and / or progressive tophi; (2) Chronic stage: The chronic gouty arthritis stage is characterized by the deposition of a large number of MSU crystals under the skin or in the joints, leading to the formation of tophi, manifested by persistent joint swelling, tenderness, deformity and dysfunction, which can cause destruction of joint bone, fibrosis of periarticular tissue, and secondary degenerative changes. The TCM syndrome diagnosis standard refers to the "gout" in the "Traditional Chinese Medicine Industry Standard of the People's Republic of China - TCM Internal Medicine Disease Diagnosis and Efficacy Standard (ZY / T001.1-94), "gout" in the "Guiding Principles for Clinical Research of New Chinese Medicines" and the "gout" syndrome differentiation diagnosis standard proposed in the "Internal Medicine of Integrated Traditional Chinese and Western Medicine". The literature data are summarized and combined with previous clinical experience to formulate the syndrome diagnosis standard. The main symptoms of refractory gout are: ① joint swelling and pain; ② subcutaneous nodules or dark purple skin; ③ repeated attacks and prolonged failure to heal. Concomitant symptoms: ① fixed stabbing pain in the joints; ② joint deformities and limited joint movement; ③ obesity; ④ fatigue; ⑤ abdominal distension; ⑥ loose stools; ⑦ dark purple tongue or pale red tongue, enlarged tongue, etc.; ⑧ white or thick and greasy yellow tongue coating; ⑨ stringy, deep, and astringent pulse, etc. The main symptoms are necessary, and a diagnosis can be made if more than 3 of the concomitant symptoms are present.

[0035] Treatment plan: Randomly divided into an intervention group and a control group, the intervention group was given the Chinese medicine composition granules prepared in Example 7 of the present invention + febuxostat tablets, and the control group was given a Chinese medicine composition placebo + febuxostat tablets. Chinese medicine composition granules: one dose per day, 400 ml taken with water, twice a day after meals; Chinese medicine composition placebo: 5% Chinese medicine composition granules + 95% dextrin, one dose per day, 400 ml taken with water, twice a day after meals; febuxostat tablets: once a day, one tablet at a time, oral. One month is a course of treatment, and three courses are used continuously.

[0036] The symptom classification criteria are shown in Table 2.

[0037] Table 2 Symptom classification criteria

[0038]

[0039] A scoring statistical method was adopted, and the improvement of each symptom was set on a 10-point scale from weak to strong. The score distribution of each symptom is shown in Table 3.

[0040] Table 3 Symptom score distribution

[0041]

[0042] The diagnosis and treatment conditions of patients of different levels after medication were divided into ineffective, effective, markedly effective and cured, with a total score of 0-4 points for ineffective, 5-16 points for effective, 17-28 points for markedly effective, and 29-40 points for cured. The clinical trial results after medication are shown in Tables 4 and 5.

[0043] Table 4 Clinical trial results after medication

[0044]

[0045] Table 5 Total effective rate and cure rate after medication (%)

[0046] Intervention Group Control group Total Effectiveness 87.50 75.00 Cure rate 64.58 37.50

[0047] Note: Total effective rate = cure rate + marked effective rate + effective rate; cure and marked effective rate = cure rate + marked effective rate

[0048] After three courses of treatment, the symptoms of most patients were effectively improved. It can be seen that the intervention group had better efficacy than the control group, especially in terms of cure rate. The intervention group was significantly better than the control group, and no obvious adverse reactions were found during the treatment.

[0049] Case record example

[0050] Case 1: The patient was 36 years old, male, with joint swelling and pain, subcutaneous nodules visible to the naked eye, dark purple color, repeated attacks, and 7 attacks of gout in the past year. He was obese, tired, bloated, purple tongue, thick and greasy yellow fur, and a stringy and slippery pulse. After taking the Chinese medicine composition granules + Febuxostat tablets orally for one month, the symptoms improved, the joint swelling and pain were relieved, gout attacked once, abdominal distension was relieved, and the tongue coating was slightly yellow. After continuing to take the medicine orally for 2 months, the subcutaneous nodules were reduced, gout did not recur, tiredness and drowsiness were relieved, abdominal distension was relieved, and the tongue coating was normal. After four weeks, all symptoms disappeared.

[0051] Case 2: The patient was 45 years old, male, with mild joint swelling and pain, small subcutaneous nodules visible to the naked eye, dark purple color, repeated attacks, and 3 attacks of gout in the past year, which did not heal over time, with abdominal distension, loose stools, dark tongue, yellow and greasy fur, and sluggish pulse. Oral Chinese medicine composition granules + Febuxostat tablets, symptoms improved after 1 month of treatment, abdominal distension was relieved, stools were formed, and the tongue coating was thin and yellow. After 2 months of treatment, the subcutaneous nodules visible to the naked eye disappeared, there was no abdominal distension, normal stools, thin white tongue coating, and no gout attacks.

[0052] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating refractory gout, characterized in that: The Chinese medicinal materials are composed of the following weight ratios: 3 parts of raw astragalus, 0.3 parts of leech, 1.5 parts of Poria, 1 part of raw Atractylodes, 1.5 parts of Ligusticum chuanxiong, 1 part of Curcuma, 1 part of Atractylodes, 3 parts of raw Coix seeds, 3 parts of Smilax glabra, 1 part of Radix Dioscoreae, 3 parts of White Peony, 1 part of Cyathula, and 0.9 parts of raw Licorice.

2. A method for preparing the Chinese medicine composition for treating refractory gout according to any one of claim 1, characterized in that: The preparation method comprises the following steps: Weigh various Chinese medicinal materials according to weight ratio and mix them; Add water and boil, combine the decoctions; Filter and concentrate to obtain a concentrate.

3. The preparation method according to claim 2, characterized in that: The concentrate is prepared as a decoction.

4. The preparation method according to claim 2, characterized in that: The preparation method further comprises the following steps: The concentrated liquid is further concentrated to a clear paste, auxiliary materials are added, and the dried material is granulated to obtain granules.

5. Use of the Chinese medicine composition according to claim 1 in preparing a medicine for treating refractory gout.

6. The use according to claim 5, characterized in that: The symptoms of the refractory gout are: (1) Joint swelling and pain, (2) subcutaneous nodules or dark purple skin, (3) repeated attacks that do not heal over time; or at least one of the following three symptoms: (1) serum uric acid level is still ≥360 μmol / L despite adequate dosage and duration of conventional uric acid-lowering drugs alone or in combination; (2) gout attacks ≥2 times / year despite standardized treatment; (3) the presence of multiple and / or progressive tophi.

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