CN115252692B

CN115252692B - Application of traditional Chinese medicine composition in preparation of medicines for treating diseases related to hyperuricemia

Info

Publication number: CN115252692B
Application number: CN202211113994.9A
Authority: CN
Inventors: 覃仁安; 石洪超; 孙东; 刘海英; 张怀; 杜群群; 何风雷; 林建云
Original assignee: Guangzhou Baiyunshan Chen Liji Pharmaceutical Factory Co ltd
Current assignee: Guangzhou Baiyunshan Chen Liji Pharmaceutical Factory Co ltd
Priority date: 2022-09-14
Filing date: 2022-09-14
Publication date: 2023-10-13
Anticipated expiration: 2042-09-14
Also published as: CN115252692A

Abstract

The invention relates to an application of a traditional Chinese medicine composition in preparing medicines for treating diseases related to hyperuricemia, and belongs to the technical field of traditional Chinese medicines. The active ingredients of the traditional Chinese medicine composition comprise the following raw materials in parts by weight: 400-800 parts of rhizoma cibotii, 150-220 parts of cherokee rose fruit, 300-420 parts of suberect spatholobus stem, 100-200 parts of philippine flemingia root, 300-420 parts of black tiger, 180-300 parts of beautiful millettia root, 20-40 parts of glossy privet fruit, 90-250 parts of mistletoe, 20-40 parts of Chinese dodder seed, 13-52 parts of rhizoma corydalis, 13-52 parts of radix zanthoxyli, 6-24 parts of frankincense and 10-30 parts of myrrh. The Chinese medicinal composition can reduce uric acid level of rats with hyperuricemia complicated with acute gouty arthritis, relieve inflammatory reaction, reduce inflammatory factor level, inhibit XOD activity, promote UA excretion, and reduce expression of related inflammatory proteins. Can be applied to preparing medicines for treating diseases related to hyperuricemia, and has better application prospect.

Description

Application of traditional Chinese medicine composition in preparation of medicines for treating diseases related to hyperuricemia

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to application of a traditional Chinese medicine composition in preparing medicines for treating diseases related to hyperuricemia.

Background

Along with the continuous improvement of the living standard and the change of the dietary structure of people, the prevalence rate of gout and hyperuricemia is in a rising trend year by year on the global scale, and the prevalence rate of gout and hyperuricemia becomes a common disease and a frequently encountered disease which seriously threaten the health of people. Gout is a group of diseases with reduced uric acid excretion caused by purine metabolic disorder and/or uric acid excretion disorder, and is characterized by hyperuricemia, recurrent acute gouty arthritis and tophus deposition, and serious cases are joint deformity and dysfunction, and chronic interstitial nephritis with acidic urinary tract calculus caused by kidneys is often involved. The disease is often aggregated with obesity, glycolipid metabolic disorder, hypertension, arteriosclerosis, coronary heart disease and the like, is one of the components of metabolic syndrome, and is one of important risk factors for the pathogenesis of cardiovascular and cerebrovascular diseases.

Currently available uric acid lowering drugs mainly comprise probenecid, sulfopirone, benzbromarone, allopurinol and the like. However, the medicines have more side effects, have obvious side effects on liver and kidney, are not suitable for long-term use, and have more hidden trouble especially for old patients to take for a long time. It is therefore an urgent need to find uric acid lowering drugs that are safe, effective and suitable for long-term administration.

With the development of modern medicine and science and technology, more and more modern researches are directed to the treatment of hyperuricemia by traditional Chinese medicine. A plurality of researches prove that the traditional Chinese medicine has better curative effect in improving clinical symptoms of patients, reducing blood uric acid level of patients and the like. In the aspect of safety, the traditional Chinese medicine has the characteristics and advantages of nature and low toxicity, the toxic and side effects of the medicine and between the medicines can be effectively reduced through the methods of medicine compatibility, processing, decoction and the like, the adverse reaction of taking is small, and the medicine is easy to be tolerated by patients. Therefore, the research of the novel medicine for treating hyperuricemia has great significance and has good treatment effect and small toxic and side effects.

Disclosure of Invention

Based on the above, it is necessary to provide an application of a traditional Chinese medicine composition in preparing medicines for treating diseases related to hyperuricemia, and the application of the traditional Chinese medicine composition in treating diseases related to hyperuricemia has a better treatment effect.

The application of a traditional Chinese medicine composition in preparing medicines for treating diseases related to hyperuricemia is disclosed, wherein the active ingredients of the traditional Chinese medicine composition comprise the following raw materials in parts by weight: 400-800 parts of rhizoma cibotii, 150-220 parts of cherokee rose fruit, 300-420 parts of suberect spatholobus stem, 100-200 parts of philippine flemingia root, 300-420 parts of black tiger, 180-300 parts of beautiful millettia root, 20-40 parts of glossy privet fruit, 90-250 parts of mistletoe, 20-40 parts of Chinese dodder seed, 13-52 parts of rhizoma corydalis, 13-52 parts of radix zanthoxyli, 6-24 parts of frankincense and 10-30 parts of myrrh.

The traditional Chinese medicine composition is derived from the pill for relaxing tendons and strengthening waist, but the original prescription has the functions of tonifying liver and kidney, strengthening tendons and bones, expelling wind and removing dampness, activating collaterals and relieving pain. It is often used for soreness of waist and knees, especially joint pain caused by exogenous wind, cold, dampness, heat, dryness, etc. The original indications of the prescription are soreness of waist and knees, sciatica caused by lumbar disc herniation and lumbar spinal stenosis, and knee osteoarthritis pain caused by knee osteoarthritis.

The inventor discovers and proves that the traditional Chinese medicine composition can reduce uric acid level of rats with hyperuricemia and acute gouty arthritis, alleviate inflammatory reaction, reduce inflammatory factor level, inhibit XOD activity, promote UA excretion and reduce expression of related inflammatory proteins.

In one embodiment, the active ingredients of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 600+ -60 parts of rhizoma Cibotii, 192+ -20 parts of fructus Rosae Laevigatae, 360+ -36 parts of caulis Spatholobi, 144+ -15 parts of radix Flemingiae Philippinensis, 360+ -36 parts of radix Rumicis, 240+ -24 parts of radix Millettiae Speciosae, 30+ -3 parts of fructus Ligustri Lucidi, 180+ -18 parts of herba Taxilli, 30+ -3 parts of semen Cuscutae, 26+ -3 parts of rhizoma corydalis, 26+ -3 parts of radix Zanthoxyli, 12+ -1 part of Olibanum, and 20+ -2 parts of Myrrha.

In one embodiment, the disease associated with hyperuricemia comprises: hyperuricemia and/or gouty arthritis.

In one embodiment, the disease associated with hyperuricemia is acute gouty arthritis caused by hyperuricemia.

In one embodiment, the traditional Chinese medicine composition achieves the effect of treating hyperuricemia complicated with acute gout arthritis by promoting uric acid excretion and reducing inflammatory response levels. Experiments show that the traditional Chinese medicine composition has the functions of promoting UA excretion, inhibiting XOD activity and reducing the expression of inflammatory proteins.

In one embodiment, the traditional Chinese medicine composition is prepared by the following method:

s1, taking woody parts of rhizoma Cibotii, fructus Rosae Laevigatae, radix Flemingiae Philippinensis and black tiger, adding water, decocting, filtering, and concentrating to obtain thick paste;

s2, taking leatherleaf milletia, millettia speciosa, glossy privet fruit, mistletoe, semen cuscutae, rhizoma corydalis, radix zanthoxyli, frankincense, myrrh and black tiger skin, and crushing by a crusher to obtain mixed coarse powder;

and S3, adding the mixed coarse powder obtained in the step S2 into the thick paste obtained in the step S1, uniformly mixing, drying, crushing into fine powder, sieving and uniformly mixing to obtain the finished product.

In one embodiment, the traditional Chinese medicine composition is prepared by the following method: in S1, adding water according to the amount of 10+/-1 g water/g medicinal material for decoction for 1-2 times, wherein each time is 1.5+/-1 h.

In one embodiment, the medicament is an oral preparation, and the medicament further comprises pharmaceutically acceptable auxiliary materials.

It is understood that specific oral formulations include tablets, capsules, pills, powders and other common dosage forms.

In one embodiment, the medicament is a pill.

In one embodiment, the pill is prepared by the following method: taking the traditional Chinese medicine composition, making pills with refined honey, coating, drying and polishing to obtain the traditional Chinese medicine composition.

Compared with the prior art, the invention has the following beneficial effects:

the traditional Chinese medicine composition disclosed by the invention can be used for reducing uric acid level of rats with hyperuricemia and acute gouty arthritis, relieving inflammatory reaction, reducing inflammatory factor level, inhibiting XOD activity, promoting UA excretion and reducing expression of related inflammatory proteins.

The traditional Chinese medicine composition can be applied to preparing medicines for treating diseases related to hyperuricemia, and has good application prospect.

Drawings

FIG. 1 is a line graph showing the effect of a Chinese medicinal composition on the degree of swelling of acute gouty arthritis rats and normal joints caused by hyperuricemia;

FIG. 2 is a photograph showing the effect of 24h of a Chinese medicinal composition on the degree of joint swelling in rats with acute gouty arthritis caused by hyperuricemia;

fig. 3 shows the effect of the Chinese medicinal composition on the morphology of ankle synovium of rats with acute gouty arthritis caused by hyperuricemia (magnification 200).

Detailed Description

In order that the invention may be readily understood, a more complete description of the invention will be rendered by reference to the appended drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.

The reagents and starting materials used in the following examples, unless otherwise indicated, were all commercially available; the methods used in the examples below, unless otherwise specified, are all conventional.

Example 1

A Chinese medicinal composition.

The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 600 parts of rhizoma cibotii, 192 parts of cherokee rose fruit, 360 parts of suberect spatholobus stem, 144 parts of philippine flemingia root, 360 parts of tiger, 240 parts of beautiful millettia root, 30 parts of glossy privet fruit, 180 parts of mistletoe, 30 parts of semen cuscutae, 26 parts of rhizoma corydalis, 26 parts of radix zanthoxyli, 12 parts of frankincense and 20 parts of myrrh.

The preparation method of the traditional Chinese medicine composition comprises the following steps:

s1, taking corresponding amounts of rhizoma Cibotii, fructus Rosae Laevigatae, radix Flemingiae Philippinensis, radix seu caulis Kadsurae Longipedunculatae and the like, adding water 10 times of the weight of the raw materials for 2 times each time, 1.5 hours each time, mixing decoctions, filtering, and concentrating to obtain thick paste;

s2, taking corresponding amounts of caulis spatholobi, radix millettiae speciosae, glossy privet fruit, chinese taxillus twig, semen cuscutae, rhizoma corydalis, radix zanthoxyli, frankincense, myrrh and black tiger skin parts, and crushing by a crusher to obtain mixed coarse powder;

Example 2

A Chinese medicinal composition in the form of pill.

Taking the traditional Chinese medicine composition prepared in the example 1, making pills with 35g of refined honey per 100g of powder, coating, drying and polishing to obtain the traditional Chinese medicine composition.

Example 3

Experimental study on pharmacodynamics of rats with hyperuricemia and acute gouty arthritis

The following Chinese medicinal compositions were prepared in example 1.

1. Experimental materials

1. Experimental animals: SD rats, SPF grade, male, weighing 180.0-220.0 g, purchased from medical laboratory animal center, guangdong province, 54 animals total.

2. A Chinese medicinal composition comprises: the preparation method comprises the steps of taking rhizoma cibotii, cherokee rose fruit, suberect spatholobus stem, radix philippinensis, black tiger, beautiful millettia root, glossy privet fruit, mistletoe, semen cuscutae, rhizoma corydalis, radix zanthoxyli, frankincense and myrrh as raw materials and weight parts, and preparing the raw materials according to the embodiment 1.

3. Reagent: xanthine Oxidase (XOD) test box (institute of biotechnology, built in south kyo); uric Acid (UA) test box (institute of bioengineering, built in south kyo); tumor necrosis factor-alpha (TNF-alpha) kit (Wohan Huamei bioengineering Co., ltd.); interleukin-10 (IL-10) kit (wuhan Huamei bioengineering limited); interleukin-1 beta (IL-1 beta) kit (Wuhan Huamei bioengineering Co., ltd.); sodium urate (mikrin); potassium oxazinate (Michelin Corp.); colchicine (Xishuangbanna edition Nakaku Co., ltd.).

2. Experimental method

1. Grouping and modeling

After 1 week of SD rat suitability feeding, weights were measured and divided into 6 groups of 9 rats, wherein 5 groups were positive group, model group, high dose group, medium dose group and low dose group, respectively, and the blank group was given an equivalent amount of physiological saline.

The method for establishing the model of hyperuricemia combined acute gouty arthritis comprises the following steps: preparing 3% potassium oxazinate, injecting into the abdominal cavity with 1mL/100g, 2 times/d, continuously injecting for 7d, starting modeling, anesthetizing the rat on the 4 th day after starting modeling, selecting the rear side of the outer side of the right ankle joint as a puncture point, puncturing the rear side of the right ankle joint of the rat to the joint cavity along the inner side of the achilles tendon at the direction of 30-40 degrees, injecting 0.05mL (25 mg/mL) sodium urate solution into the joint cavity after feeling of falling empty, and inducing an acute gouty Arthritis (AUG) model by taking the bulge of the opposite side of the joint capsule as an injection standard.

The rats showed lameness, swelling of joints, inability to bear load after injection, and were considered successful in molding. The same site of the normal group was injected with the same volume of 0.9% physiological saline. The data in tables 1, 2, 3 and 4, which are related to the model group and the blank group, are all significantly different, which indicates that the study modeling is successful.

2. Administration of drugs

After the primary injection of the potassium oxazinate, the administration is carried out for 7 days. Blank group and model group, and lavage equal volume of physiological saline; the positive group was given 0.05mg/100g colchicine; the traditional Chinese medicine composition prepared according to the embodiment 1 is divided into: low dose group (75 mg/100 g), medium dose group (150 mg/100 g) and high dose group (300 mg/100 g), 9 rats per group.

3. Viewing items

1. General index: general state, mental state, etc. of rats, record body mass.

2. Changes in joint swelling degree: before molding and after molding, 2h, 4h, 8h, 24h and 48h are respectively measured by vernier calipers, the length and width of the same part of the ankle joint of the right hind limb are measured, the circumference is calculated (average value is taken), and the swelling rate is calculated.

Swelling ratio (%) = (peri-inflammatory ankle-peri-inflammatory ankle)/peri-inflammatory ankle×100%.

3. Rat gait score and joint inflammation index assessment

Gait scoring: level 0 (0 point): can walk normally; stage 1 (1 part): lameness, lower limb bending; stage 2 (2): the walking is limp, and the lower limbs can only contact the ground; stage 3 (3): severe lameness, and no tripodia walking on the ground.

Index of joint inflammation: level 0 (0 point): the joint part is normal, and swelling does not occur; stage 1 (2): redness and swelling of the joint skin with obvious bony signs; grade 2 (4): redness and swelling of joint skin and joint parts; stage 3 (6): redness and swelling appear in both the inner and outer positions of the joint.

4. Rat ankle synovial membrane pathology observation

The joint synovial tissue is fixed in 4% paraformaldehyde solution, dehydrated by gradient alcohol, embedded by conventional paraffin, sectioned by 5 mu m, and observed under a microscope after HE staining for pathological changes of the joint synovial tissue.

5. Detection of rat biochemical index

1h after the last administration, the abdominal aorta was bled, centrifuged for 10min (3 000r/min), and serum was taken. Serum UA was assayed by enzymatic colorimetric method, serum XOD was assayed by colorimetric method, and serum TNF- α, IL-1β and IL-10 were assayed by Elisa method.

6. Statistical treatment

The experimental results were analyzed using SPSS 20.0 software and the data description was given using x±s, where x is the average value and the comparisons were made using the t-test. P < 0.05 indicates significant statistical differences and P < 0.01 indicates very significant statistical differences.

4. Experimental results

1. General index

Through observation, in the experimental process, the rat has good state, normal mental state and no obvious difference in weight.

2. Rat gait score and joint inflammation index assessment

The results of the rat gait score and joint inflammation index evaluation are shown in the following table.

Table 1. Effects of traditional Chinese medicinal composition on gait score and inflammation index of hyperuricemia-complicated acute gouty arthritis rats (n=9,)

note that: p < 0.05, P < 0.01 compared to model group.

The above results show that the gait scores of the high, medium, low and positive groups of the Chinese medicinal composition were significantly lower than that of the model group, without statistical differences (P > 0.05) from the positive group. The traditional Chinese medicine composition provided by the invention can obviously improve the gait and joint inflammation indexes of rats, and the effect is better than that of positive medicines.

3. Changes in joint swelling degree and changes in joint synovial membrane

The results of the changes in the swelling degree of the joints of rats are shown in the following table and fig. 1-2.

Table 2. Effects of the Chinese medicinal composition on joint swelling degree in hyperuricemia-complicated acute gouty arthritis rats (n=9,)。

note that: comparing with model group, P < 0.05, P < 0.01; in comparison with the positive group, ^# P＜0.05， ^## P＜0.01。

fig. 1 is a line graph showing the effect of a Chinese medicinal composition on the degree of swelling of a rat with hyperuricemia complicated with acute gouty arthritis and normal joints, and fig. 2 is a photograph showing the degree of swelling of the rat joints at 24 hours. Fig. 3 is a morphological micrograph (200 magnification microscopic observation) of the rat ankle synovium at day seven.

The above results show that at 24h, the positive and high dose groups showed significantly lower joint swelling than the model group; at 48h, the joint swelling degree of the positive group and the high-dose group is significantly lower than that of the model group, the joint swelling degree of the low-dose group and the medium-dose group is significantly higher than that of the positive group, and no statistical difference (P > 0.05) exists between the positive group and the high-dose group.

4. Rat biochemical index detection result

The biochemical index detection results of the rats are shown in the following table.

Table 3. Effects of the Chinese medicinal composition on hyperuricemia-complicated acute gouty arthritis rats UA and XOD (n=9,)。

the above results indicate that the positive group and the high, medium, and low dose groups UA were lower than the model group, while there was no statistical difference (P > 0.05) between the positive group and the high, medium, and low dose groups.

The positive group and the high, medium and low XOD groups were lower than the model group, there was no statistical difference (P > 0.05) between the positive group and the high, medium and low XOD groups, whereas the positive group XOD was lower than the low dose group.

Table 4. Effects of the Chinese medicinal composition on TNF-alpha and IL-10 and IL-1 beta in hyperuricemia-complicated acute gouty arthritis rats (n=9,)。

the positive and high and medium dose groups were all lower in TNF- α than the model group, while there was no statistical difference (P > 0.05) between positive and high, medium and low dose groups.

IL-10 was lower in the positive and high, medium and low dose groups than in the model group, while there was no statistical difference (P > 0.05) between the positive and high, medium and low dose groups.

The positive group and the high-dose group, the medium-dose group and the low-dose group are lower in IL-1β than the model group, and the positive group is lower in IL-1β than the medium-dose group and the low-dose group.

The results show that the traditional Chinese medicine composition can reduce uric acid level of rats with hyperuricemia complicated with acute gouty arthritis, reduce inflammatory factor level, inhibit XOD activity and promote UA excretion, thereby achieving the treatment effect.

The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.

The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims

1. The application of the traditional Chinese medicine composition in preparing medicines for treating diseases related to high uric acid comprises the following raw material medicines in parts by weight: 400-800 parts of rhizoma cibotii, 150-220 parts of cherokee rose fruit, 300-420 parts of suberect spatholobus stem, 100-200 parts of philippine flemingia root, 300-420 parts of black tiger, 180-300 parts of beautiful millettia root, 20-40 parts of glossy privet fruit, 90-250 parts of mistletoe, 20-40 parts of Chinese dodder seed, 13-52 parts of rhizoma corydalis, 13-52 parts of radix zanthoxyli, 6-24 parts of frankincense and 10-30 parts of myrrh.

2. The use according to claim 1, wherein the raw materials of the traditional Chinese medicine composition are, in parts by weight: 600+ -60 parts of rhizoma Cibotii, 192+ -20 parts of fructus Rosae Laevigatae, 360+ -36 parts of caulis Spatholobi, 144+ -15 parts of radix Flemingiae Philippinensis, 360+ -36 parts of radix Rumicis, 240+ -24 parts of radix Millettiae Speciosae, 30+ -3 parts of fructus Ligustri Lucidi, 180+ -18 parts of herba Taxilli, 30+ -3 parts of semen Cuscutae, 26+ -3 parts of rhizoma corydalis, 26+ -3 parts of radix Zanthoxyli, 12+ -1 part of Olibanum, and 20+ -2 parts of Myrrha.

3. The use according to claim 1, wherein the disease associated with hyperuricemia comprises: hyperuricemia and/or gouty arthritis.

4. The use according to claim 1, wherein the disease associated with hyperuricemia is acute gouty arthritis caused by hyperuricemia.

5. The use according to claim 4, wherein the Chinese medicinal composition achieves the effect of treating hyperuricemia complicated with acute gouty arthritis by promoting uric acid excretion and reducing the level of inflammatory response.

6. The use according to claim 1, wherein the Chinese medicinal composition is prepared by the following method:

7. The use according to claim 6, wherein the Chinese medicinal composition is prepared by the following method: in S1, adding water according to the amount of 10+/-1 g water/g medicinal material for decoction for 1-2 times, wherein each time is 1.5+/-1 h.

8. The use according to claim 1, wherein the medicament is an oral formulation, and wherein the medicament further comprises pharmaceutically acceptable excipients.

9. The use according to claim 8, wherein the medicament is a pill.

10. The use according to claim 9, wherein the pill is prepared by the following method: taking the traditional Chinese medicine composition, making pills with refined honey, coating, drying and polishing to obtain the traditional Chinese medicine composition.