CN112353909A

CN112353909A - Traditional Chinese medicine composition for preventing and treating gout and preparation method and application thereof

Info

Publication number: CN112353909A
Application number: CN202011436835.3A
Authority: CN
Inventors: 寇俊萍; 张媛媛; 王慧敏; 许梦晨; 李旺
Original assignee: China Pharmaceutical University
Current assignee: China Pharmaceutical University
Priority date: 2020-12-10
Filing date: 2020-12-10
Publication date: 2021-02-12

Abstract

The invention discloses a traditional Chinese medicine composition for preventing and treating gout and a preparation method and application thereof. According to the application, chicory, coix seeds, medlar, Chinese yam, sophora japonica and kudzu roots are selected to form the composition according to homology of medicine and food, and experiments prove that the composition can reduce uric acid and protect kidney functions, can obviously inhibit the activity of xanthine oxidase and inhibit the generation of uric acid, has a relieving effect on swelling of ankle joints of mice, has an anti-inflammatory effect, and can be used for developing and preparing medicines for preventing and treating gout. The components of the composition are all from a list of homology of medicine and food issued by Weijian Commission, so that the composition has small toxic and side effects, good patient compliance and easy popularization; the composition is simple to prepare, convenient to operate and applicable to industrial production.

Description

Traditional Chinese medicine composition for preventing and treating gout and preparation method and application thereof

Technical Field

The invention relates to a traditional Chinese medicine technology, in particular to a traditional Chinese medicine composition for preventing and treating gout and a preparation method and application thereof.

Background

Gout is a group of clinical symptoms caused by urate crystallization and deposition on tissues or organs, has the characteristics of high morbidity and multiple complications, has increasingly obvious trend of youthfulness, and seriously reduces the quality of life of patients ((1) Robinson P C]Maturitas,2018,118: 67-73.). Gout is divided into hyperuricemia period, gouty arthritis attack period, tophus and gouty nephropathy period ((2) Dalbeth N, Stamp L. hyperuricemia and gout: time for a new starting system]Ann Rheum Dis,2014,73(9): 1598-1600.). Hyperuricemia is a metabolic disease caused by purine metabolic disorder or decreased uric acid excretion, and is characterized by abnormally elevated blood uric acid levels. The clinical diagnosis standard refers to that under the normal purine diet state, the fasting blood uric acid level of non-same day is higher than 420 mu mol/L in male, and higher than 360 mu mol/L in female ((3) Li X, Liu J, Ma L et al]Eur J Med Chem,2019,166: 186-196.). When uric acid is saturated, sodium urate crystals are formed and deposited on joints and surrounding soft tissues, and gouty arthritis is caused. Gouty arthritis is the most common first symptom of gout, and is characterized by a deformed joint with red swelling and hot pain in the patient at the time of attack, which places a huge burden on the patient and his family ((4) Martillo MA, Nazzal L, criticden db]Curr Rheumatol Rep,2014,16(2): 400.). In developed countries, 1% of the population suffers from gouty arthritis. Therefore, it is important to reduce urate levels and joint inflammation in gout patients by various routes ((5) Cleophas M C,

TO,Lemmers H,et al.Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases[J].Ann Rheum Dis,2016,75(3):593-600.)。

at present, gout is mainly treated by reducing uric acid, resisting inflammation and relieving pain, the treatment method is mainly drug treatment, and severe patients need surgical treatment ((6) plum, cinnabar, Dayuxiang and the like, Chinese hyperuricemia related disease diagnosis and treatment multidisciplinary experts have consensus [ J ] China journal of internal medicine, 2017,56(3):235-246 ]). The therapeutic drugs in the hyperuricemia period are mainly xanthine oxidase inhibitors, and are represented by allopurinol and febuxostat, but allopurinol can cause skin anaphylaxis and liver and kidney function damage, and febuxostat can also cause anaphylaxis of individual patients, and simultaneously has unpredictable cardiovascular risks ((7) Mancera RL, Luna G, Dolzhenko AV, et al, inhibitors of xanthine oxidase: scaffold diversity and structure-based drug design [ J ]. ChemMedm, 2019,14(7):714 and 743). The uricosuric drug benzbromarone, also has hepatotoxicity ((8) Bernhard H, Theo K, Stephan R, et al. Benzbromorarone: a double-digested shock cut the live? [ J ]. Eur J Gastroenterol Heapotol, 2013,25(1): 119-. Non-steroidal anti-inflammatory drugs, colchicine, and glucocorticoids are commonly used to relieve inflammation and pain during acute gout attacks, but these drugs have many adverse reactions ((9) Liuyu, pleasure, Juxian, etc. foreign guidelines for gout treatment have evolved and compared [ J ] J. The traditional Chinese medicine has the characteristics of multiple components and multiple target points, and has unique advantages in the aspects of preventing and treating gout.

The Chinese has the habit of homology of medicine and food all the time, and the homology of medicine and food has good patient compliance due to small toxic and side effect, has considerable market and gradually becomes a hotspot of research.

Disclosure of Invention

The purpose of the invention is as follows: aiming at the prior art, the invention provides a traditional Chinese medicine composition for preventing and treating gout, which is homologous in medicine and food, and a preparation method and pharmaceutical application thereof.

The technical scheme is as follows: the traditional Chinese medicine composition for preventing and treating gout comprises the following components in parts by weight: 4-8 parts of chicory, 3-6 parts of coix seeds, 3-6 parts of medlar, 3-6 parts of Chinese yam, 1-3 parts of sophora flower buds and 1-3 parts of kudzu roots.

The application also provides a preparation method of the traditional Chinese medicine composition for preventing and treating gout, which comprises the following steps: mixing the traditional Chinese medicines according to the proportion of 1: 10, adding distilled water, soaking for 30 minutes, decocting for 2-3 times, each time for 1 hour, combining the decoction, sieving the decoction by a pharmacopeia No. 9 sieve, and concentrating by a rotary evaporator.

The invention also discloses application of the traditional Chinese medicine composition in preparing a medicine for preventing and treating gout.

Wherein the gout is in an asymptomatic hyperuricemia period, an acute gouty arthritis attack period, a non-attack period of sodium urate deposited in joints, a tophus, a gouty nephropathy period and the like.

The invention also discloses application of the traditional Chinese medicine composition in preparing health-care products for relieving gout.

Wherein the health product is bagged tea, biscuit, porridge, and bread.

Gout is a metabolic disease of sodium urate crystals deposited in joints and surrounding soft tissues, and the acute attack stage of gout is often manifested by red swelling and hot pain of joint tissues of patients. Traditional Chinese medicine considers that gout belongs to the category of arthralgia in a broad sense, and is caused by disharmony between nutrient and defensive qi, weakness of spleen and stomach, endogenous dampness and heat and joint fluid injection due to overeating, acid and salt and damaging liver and kidney. In the traditional Chinese medicine composition, the chicory and the coix seeds have the effects of inducing diuresis to alleviate edema, invigorating spleen to promote digestion, and the medlar and the Chinese yam can nourish liver, protect liver, tonify lung and spleen, and the sophora flower bud can clear blood and cool blood and the radix puerariae can release muscles and defervesce as auxiliary materials. The Chinese medicinal composition has effects of inducing diuresis to alleviate edema, invigorating spleen and qi, eliminating arthralgia and removing fever.

Has the advantages that: compared with the prior art, according to homology of medicine and food, the composition is prepared from chicory, coix seed, medlar, Chinese yam, sophora flower bud and kudzu vine root, and experiments prove that the composition has the effects of reducing uric acid and protecting kidney function, can obviously inhibit the activity of xanthine oxidase and the generation of uric acid, has a relieving effect on swelling of ankle joints of mice, has an anti-inflammatory effect, and can be used for developing and preparing medicines for preventing and treating gout. Moreover, all components of the composition come from a list of homology of medicine and food issued by Weijian Commission, so that the composition has small toxic and side effects, good patient compliance and easy popularization; the composition is simple to prepare, convenient to operate and applicable to industrial production.

Drawings

FIG. 1 shows the effect of the Chinese medicinal composition on uric acid, creatinine and urea nitrogen in the serum of hyperuricemia in mice induced by Potassium Oxonate;

FIG. 2 shows the effect of the Chinese medicinal composition on uric acid, creatinine and urea nitrogen in hyperuricemia urine of mice induced by Potassium Oxonate;

FIG. 3 the effect of the Chinese medicinal composition on xanthine oxidase activity in liver of potassium oxonate-induced hyperuricemia in mice;

FIG. 4 the effect of the Chinese medicinal composition on acute inflammatory paw swelling of mice caused by carrageenan;

FIG. 5 shows the effect of the Chinese medicinal composition on IL-1 beta and TNF-alpha in the serum of acute inflammation of mice caused by carrageenan.

Detailed Description

The present invention will be further described with reference to the following examples. The following examples are experimental methods without specifying specific conditions, and generally follow the methods known in the art. The test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified.

In the examples, decoction pieces of chicory, coix seed, medlar, yam, sophora flower bud and kudzu root are all purchased from Nanjing Shangyoutang pharmaceutical Co., Ltd. In the attached drawings, the traditional Chinese medicine composition is abbreviated as KS.

Example 1

The traditional Chinese medicine composition of the embodiment consists of the following traditional Chinese medicine decoction pieces in weight gram: 6 g of chicory, 4 g of coix seed, 4 g of medlar, 4 g of yam, 2g of sophora flower bud and 1g of kudzu root.

The preparation method comprises the following steps: mixing the traditional Chinese medicines according to the proportion of 1: adding distilled water according to the volume ratio of 10, soaking for 30 minutes, decocting for 2 times, each time for 1 hour, combining the soup, sieving the soup by a pharmacopoeia No. 9 sieve, and concentrating to 2g/ml by a rotary evaporator. When used, the extract is diluted with distilled water to the desired concentration, such as 1g/ml, 0.5 g/ml.

Example 2

The traditional Chinese medicine composition of the embodiment consists of the following traditional Chinese medicine decoction pieces in weight gram: 4 g of chicory, 3 g of coix seed, 3 g of medlar, 3 g of yam, 1g of sophora flower bud and 1g of kudzu root.

The preparation method is the same as example 1.

Example 3

The traditional Chinese medicine composition of the embodiment consists of the following traditional Chinese medicine decoction pieces in weight gram: chicory 8 g, coix seed 6 g, matrimony vine 6 g, Chinese yam 6 g, pagodatree flower bud 3 g, kudzu vine root 3 g.

The preparation method is the same as example 1.

Example 4

Example 1 Effect of the Chinese medicinal composition KS in ameliorating Potassium Oxonate-induced hyperuricemia in mice

a) Animal grouping and drug intervention

SPF male Kunming mice 18-22 g, purchased from Sibefu (Beijing) Biotechnology Ltd, license number SCXK (Beijing) 2019-. The groups were randomly divided into 6 groups, namely blank group, model group, low, medium and high dosage groups of the Chinese medicinal composition, and febuxostat group, and each group had 8 animals.

(1) Blank group: mice were gavaged continuously with saline for 14 days.

(2) Model group: mice were gavaged continuously with saline for 14 days.

(3) The low-dose group of the traditional Chinese medicine composition comprises: the mice were gavaged with 0.5g/ml of the herbal composition at a dose volume of 0.1ml/10g for 14 consecutive days.

(4) The traditional Chinese medicine composition comprises the following dosage groups: the mice were gavaged with 1g/ml of the Chinese medicinal composition at a dose volume of 0.1ml/10g for 14 days.

(5) High dose group of Chinese medicinal composition: the mice were gavaged with 2g/ml of the herbal composition at a dose volume of 0.1ml/10g for 14 consecutive days.

(6) Febuxostat group: the mice were gavaged continuously with 0.6mg/ml febuxostat at a dosing volume of 0.1ml/10g for 14 days.

b) Potassium oxonate induced hyperuricemia in mice

From day 8, the blank group was subjected to intraperitoneal injection of physiological saline for 7 consecutive days, and the remaining 5 groups were subjected to intraperitoneal injection of potassium oxonate at a concentration of 500mg/kg for 7 consecutive days to prepare a hyperuricemia mouse model.

c) Detection of uric acid, creatinine and urea nitrogen in urine

And (3) on the 13 th day, filling corresponding drugs into the stomach, injecting oteracil potassium into the abdominal cavity for molding, putting the mouse into a metabolism cage, collecting urine of the mouse within 24h, centrifuging for 10 minutes at 3000rmp, separating supernatant, and detecting the content of uric acid, creatinine and urea nitrogen in the supernatant by using the kit.

d) Detection of uric acid, creatinine and urea nitrogen in mouse serum

One hour after the molding on day 14, the eyeballs of the mice in each group are picked and blood is taken, after the mice are stood for 30 minutes, the mice are centrifuged at 3500rmp for 15 minutes, supernatant is separated, and the kit detects the levels of uric acid, creatinine and urea nitrogen in the mice.

e) Detection of xanthine oxidase in liver

Dissecting the mouse after blood collection, collecting about 0.1g of liver lobules, and mixing the raw materials according to the weight ratio of 1: adding physiological saline into the mixture according to the volume ratio of 9, transferring the mixture into a homogenizer for grinding, centrifuging the homogenate liquid at 3000rmp for 10 minutes, taking the supernatant, and detecting the activity of the xanthine oxidase in the liver according to the kit specification.

Results of the experiment

a) Influence of traditional Chinese medicine composition on uric acid, creatinine and urea nitrogen in serum of hyperuricemia mouse

As shown in figure 1 of the drawings, in which,

^#P<0.05vs. blank set;^##P<0.01vs. blank set; p<0.05vs. model set; p<0.01vs. model set. As can be seen from fig. 1, compared with the blank group, the serum uric acid level in the model group is significantly increased, and the creatinine and urea nitrogen levels are also significantly increased, which indicates that the renal function is decreased, the Chinese medicinal composition is alleviated after administration, and the high-dose group has significant differences. Although the effect of reducing uric acid of the traditional Chinese medicine composition is not as remarkable as that of febuxostat, the traditional Chinese medicine composition has the effects of reducing uric acid and protecting kidney function.

b) Influence of traditional Chinese medicine composition on uric acid, creatinine and urea nitrogen in urine of hyperuricemia mouse

As shown in fig. 2, (X ± SD, n ═ 8).^##P<0.01vs. blank set; p<0.05vs. model set; p<0.01vs. model set. As can be seen from fig. 2, compared with the blank group, the levels of uric acid level, creatinine and urea nitrogen in urine in the model group were significantly reduced, and the high-dose group of the gastric lavage traditional Chinese medicine composition was significantly improved, indicating that the high-dose group could promote uric acid excretion. Compared with the febuxostat group, the model group has no significant difference, and the effect of the febuxostat on reducing the uric acid is unrelated to the promotion of uric acid excretion.

c) Influence of traditional Chinese medicine composition on xanthine oxidase in liver of hyperuricemia mouse

As shown in figure 3 of the drawings,

^##P<0.01vs. blank set; p<0.01vs. model set. The results in fig. 3 show that after potassium oxonate molding, the activity of xanthine oxidase in liver is obviously increased, uric acid production is increased, and the high-dose group and febuxostat group of the traditional Chinese medicine composition can obviously inhibit the activity of xanthine oxidase and uric acid production.

The research results in this section show that the traditional Chinese medicine composition can reduce the blood uric acid of hyperuricemia mice, and the effect of the traditional Chinese medicine composition can be related to the inhibition of the activity of xanthine oxidase and the promotion of uric acid excretion.

Example 5

Example 1 Effect of KS, a Chinese medicinal composition, on ameliorating acute inflammation of mouse caused by Carrageenan

Experimental methods

a) Animal grouping and drug intervention

SPF grade male ICR mice, 18-22 g, were purchased from the university of Yangzhou, center of comparative medicine, license number SYXK (Su) 2018-. The group was divided into 4 groups, including blank group, model group, Chinese medicinal composition, and dexamethasone group.

(1) Blank group: mice were gavaged continuously with saline for 7 days.

(2) Model group: mice were gavaged continuously with saline for 7 days.

(3) The traditional Chinese medicine composition comprises the following components: the mice were gavaged with 1g/ml of the Chinese medicinal composition at a dose volume of 0.1ml/10g for 7 days.

(4) Dexamethasone group: mice were gavaged with 0.5mg/ml dexamethasone at a dose volume of 0.1ml/10g for 7 consecutive days.

b) Preparation of carrageenan-induced inflammation model

After 1 hour after completion of the gavage on the seventh day, 25. mu.l of 1% carrageenan was injected into the plantar aspect of the right hind paw of each group of mice, except for the blank group, which was injected with an equal volume of physiological saline.

c) Influence of traditional Chinese medicine composition on foot swelling caused by acute inflammation of mice due to carrageenan

The ankle circumference of the mouse was measured with a vernier caliper at 0, 1, 2, 3, 4, and 5 hours after carrageenan or physiological saline injection, respectively, and the degree of foot swelling was calculated.

Swelling degree (%) - (circumference at-0)/circumference at 0%

d) Influence of traditional Chinese medicine composition on IL-1 beta and TNF-alpha in serum of carrageenan-induced inflammatory mice

After 5 hours of measurement of the circumference of the ankle joint of the mouse is finished, the eyeball is picked to draw blood, the blood is kept still for 30 minutes at room temperature, the blood is centrifuged for 15 minutes at 3000rmp, the supernatant is separated, and the level of IL-1 beta and TNF-alpha in the blood serum is detected according to an ELISA instruction.

Results of the experiment

a) Improvement of acute inflammation foot swelling of mice caused by carrageenan by traditional Chinese medicine composition

As shown in fig. 4, (X ± SD, n ═ 8). The results in figure 4 show that after carrageenan injection, the ankle swelling of the mice is increased firstly and then decreased, and reaches the maximum in 1 hour, and the traditional Chinese medicine composition and dexamethasone have a certain relieving effect on the ankle swelling of the mice.

b) Improving effect of traditional Chinese medicine composition on IL-1 beta and TNF-alpha in serum of carrageenan-induced inflammation mice

As shown in fig. 5, (X ± SD, n ═ 8).^##P<0.01vs. blank set; p<0.01vs. model set. The results of figure 5 show that the levels of IL-1 beta and TNF-alpha in the serum of the mice in the model group are obviously increased, and the condition of the pre-administration group of the traditional Chinese medicine composition is obviously improved, which preliminarily explains the anti-inflammatory effect of the traditional Chinese medicine composition.

The research results show that the traditional Chinese medicine composition can improve the foot swelling of carrageenan-induced inflammatory mice and IL-1 beta and TNF-alpha in serum, and has an anti-inflammatory effect.

Claims

1. The traditional Chinese medicine composition for preventing and treating gout is characterized by comprising the following components in parts by weight: 4-8 parts of chicory, 3-6 parts of coix seeds, 3-6 parts of medlar, 3-6 parts of Chinese yam, 1-3 parts of sophora flower buds and 1-3 parts of kudzu roots.

2. The method for preparing a Chinese medicinal composition for preventing and treating gout according to claim 1, comprising the steps of: weighing the components according to the formula ratio, soaking in water, decocting for 2-3 times, mixing the decoctions, filtering, and rotary evaporating.

3. The use of the Chinese medicinal composition of claim 1 for the preparation of a medicament for the prevention and treatment of gout.

4. The use according to claim 3, wherein said gout is during periods of asymptomatic hyperuricemia, during episodes of acute gouty arthritis, during non-episodes of sodium urate deposition in joints, tophus, and gouty nephropathy.

5. The use of the Chinese medicinal composition of claim 1 in the preparation of a health product for relieving gout.

6. The use of claim 5, wherein the health product is a teabag, a biscuit, porridge, bread.