CN115006475A

CN115006475A - Composition and application thereof in medicines for preventing and treating hyperuricemia and protecting liver and kidney

Info

Publication number: CN115006475A
Application number: CN202210344924.8A
Authority: CN
Inventors: 廖琼峰; 蔡凯伟; 陈烨
Original assignee: Guangzhou University of Traditional Chinese Medicine
Current assignee: Guangzhou University of Traditional Chinese Medicine
Priority date: 2022-03-31
Filing date: 2022-03-31
Publication date: 2022-09-06
Anticipated expiration: 2042-03-31
Also published as: CN115006475B

Abstract

The invention discloses a composition and application thereof in medicines for preventing and treating hyperuricemia and protecting liver and kidney, and relates to the technical field of biological medicines. The traditional Chinese medicine composition is prepared from the astragalus and the arrowroot according to a set ratio, and comprises 0.5-1.5 parts of the astragalus and 0.5-3 parts of the arrowroot according to parts by weight.

Description

Composition and application thereof in medicines for preventing and treating hyperuricemia and protecting liver and kidney

Technical Field

The invention relates to the technical field of biological medicines, in particular to a composition and application thereof in medicines for preventing and treating hyperuricemia and protecting liver and kidney.

Background

Hyperuricemia (HUA) is a metabolic disease in which abnormal purine metabolism in vivo causes an increase in uric acid production or an abnormal uric acid excretion, resulting in an abnormal increase in serum uric acid level, and a continuous increase in uric acid content causes accumulation of urate single crystals mainly in joints and peripheral tissues in vivo, leading to the development of nephropathy or gout. The early symptoms of patients with hyperuricemia are represented by abnormal indexes related to uric acid in serum, and the later symptoms are represented by kidney injury, normal joint tissue morphological deformation and the like. With the improvement of living standard, the prevalence rate of hyperuricemia has a very obvious rising trend, and is the second largest metabolic disease next to diabetes. In addition, recent research shows that the high uric acid index not only causes diseases of kidney and joint parts, but also causes of other metabolic diseases such as hyperlipidemia, hyperglycemia and the like, and has serious influence on the public life and life health.

At present, although there are many drugs for reducing uric acid in the market, the drugs can be mainly divided into western medicines for inhibiting uric acid, promoting uric acid excretion and generation, and resisting inflammation, immunity and defervescence. Inhibiting uric acid production, i.e., inhibiting cyclooxygenase production (e.g., allopurinol tablets), and blocking uric acid production during production to thereby lower uric acid levels; uric acid excretion promoting drugs (such as benzbromarone) accelerate uric acid excretion by accelerating renal excretion function, thereby reducing uric acid level; the anti-inflammatory, anti-immune and anti-fever western medicines mainly comprise glucocorticoid medicines (such as colchicine), which are mainly used for treating severe gout developed in later period of hyperuricemia patients and relieve symptoms by anti-inflammatory and analgesia. Although the modes of reducing uric acid are different, the medicines have obvious side effects, for example, the medicines are accompanied by serious liver and kidney damage, gastrointestinal adverse reactions, skin allergy, immunosuppression and other adverse reactions after being taken, and are not suitable for long-term taking.

In view of the above, the present invention is particularly proposed.

Disclosure of Invention

The invention aims to provide a composition and application thereof in medicines for preventing and treating hyperuricemia and protecting liver and kidney.

The invention is realized by the following steps:

in a first aspect, an embodiment of the present invention provides an application of a composition in a drug for preventing and treating hyperuricemia, where the composition includes, in parts by weight: 0.5-1.5 parts of astragalus and 0.5-3 parts of arrowroot.

In a second aspect, embodiments of the present invention provide the use of a composition in a medicament for protecting the liver and kidney, the composition being in the use as described in the preceding embodiments.

In a third aspect, the embodiments of the present invention provide a use of a composition in a medicament for preventing and treating hyperuricemia and protecting liver and kidney, wherein the composition is the composition in the use as described in the previous embodiments.

In a fourth aspect, the embodiment of the invention provides a composition, which comprises, by weight, 0.5-1.5 parts of astragalus membranaceus and 0.5-3 parts of arrowroot.

The invention has the following beneficial effects:

the traditional Chinese medicine composition is prepared from the astragalus and the arrowroot according to a set proportion, has an obvious improvement effect on treating hyperuricemia, has an obvious effect of protecting the kidney while reducing uric acid, and provides a new way for preventing and treating the hyperuricemia.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.

FIG. 1 is serum uric acid UA concentration (. mu. mol/L);

FIG. 2 is serum creatinine CRE concentration (. mu. mol/L);

FIG. 3 is the serum urea nitrogen BUN concentration (mmol/L);

FIG. 4 shows the concentration (U/L) of xanthine oxidase XOD in serum;

FIG. 5 is a graph of serum alanine Aminotransferase (ALT) concentration (U/L); wherein, ^# P<0.05， ^## P<0.01 compared to the model set, ^* P<0.05， ^** P<0.01 compared to the normal group;

FIG. 6 shows pathological changes (fold: 20X 10) in renal HE sections of mice in each group.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

Aiming at the problem of great side effect of the existing clinical uric acid reducing medicine, the invention aims at solving the problems of effectively treating hyperuricemia and protecting liver and kidney from the aspect of traditional Chinese medicine, and provides the preparation method of the composition. The composition is a medicine-food homologous traditional Chinese medicine, can be taken for a long time, has the effects of preventing and improving and treating hyperuricemia, has the multi-target effect, can integrally treat diseases, has high safety and the like.

The embodiment of the invention provides an application of a composition in a medicine for preventing and treating hyperuricemia, wherein the composition comprises the following components in parts by weight: 0.5-1.5 parts of astragalus and 0.5-3 parts of arrowroot.

Radix astragali is sweet in taste and slightly warm in nature, and has the effects of invigorating qi, invigorating yang, inducing diuresis and relieving swelling. Radix astragali mainly contains astragalus polysaccharides, astragalus saponin and flavonoids such as calycosin glucoside and the like, and has an important effect on treating gout. The arrowroot is sweet and light in taste and cool in nature, and has the effects of clearing lung heat, relieving cough, clearing heat and promoting urination. Often appearing in the form of arrowroot powder, and the main components are polysaccharide and the like. Based on early-stage in vitro experiments, after different mass proportions of astragalus mongholicus and arrowroot and drug effects are compared, the invention provides the medicinal and edible traditional Chinese medicine composition for treating hyperuricemia, and related drug effect verification is carried out in an animal body.

The proportion of the two medicines in the composition is strictly selected, and the composition has obvious influence on the exertion of the drug effect and the normal use.

Specifically, the astragalus may be any one or a mixture of any two of 0.5 parts, 0.6 parts, 0.7 parts, 0.8 parts, 0.9 parts, 1.0 parts, 1.1 parts, 1.2 parts, 1.3 parts, 1.4 parts and 1.5 parts by weight.

The arrowroot can be any one or a range between any two of 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1.0 part, 1.1 part, 1.2 parts, 1.3 parts, 1.4 parts, 1.5 parts, 1.6 parts, 1.7 parts, 1.8 parts, 1.9 parts, 2.0 parts, 2.1 parts, 2.2 parts, 2.3 parts, 2.4 parts, 2.5 parts, 2.6 parts, 2.7 parts, 2.8 parts, 2.9 parts and 3.0 parts.

Preferably, the composition comprises, in parts by weight: 0.5-1.5 parts of astragalus and 0.5-1.5 parts of arrowroot. In the preferred range, the composition has a better preventive or therapeutic effect on hyperuricemia.

The astragalus may be, without limitation, a medicinal astragalus or an extract of astragalus. Preferably, the astragalus is an astragalus extract.

Preferably, the extraction method of the astragalus extract comprises the following steps: decocting radix astragali in water, filtering, collecting filtrate, and drying to obtain radix astragali extract.

Preferably, the mixing volume ratio of the astragalus root to the water is 1: (6-8), specifically 1: 6. 1: 7 and 1: 8, or a range between any two.

Preferably, the decocting time is 1-3 h, and specifically, the decocting time can be any one or any two of 1h, 1.5h, 2h, 2.5h and 3 h.

Preferably, the extraction method further comprises decocting the decocted residue with water at least once, mixing the filtrate obtained after decocting and filtering with the previous filtrate, and drying to obtain the astragalus extract.

The arrowroot can be arrowroot itself or a processed product thereof without limitation. Preferably, the arrowroot comprises arrowroot powder.

Preferably, the preparation method of the arrowroot powder comprises the following steps: adding water into peeled arrowroot, crushing, filtering to obtain a mixed aqueous solution, standing, taking a precipitate, and drying to obtain the arrowroot powder.

Preferably, the composition further comprises water, which is capable of better mixing the astragalus and arrowroot.

Preferably, the water is added in an amount of: adding 20-100mL of water into the mixture of every 1g of astragalus and arrowroot. Specifically, 20mL, 30mL, 40mL, 50mL, 60mL, 70mL, 80mL, 90mL, or 100mL or a range between any two thereof may be added to 1g of the mixture of astragalus and arrowroot.

The embodiment of the invention also provides application of a composition in a medicament for protecting liver and kidney, wherein the composition is applied as in any embodiment.

The embodiment of the invention also provides application of a composition in medicines for preventing and treating hyperuricemia and protecting liver and kidney, wherein the composition is the composition in the application as described in any embodiment.

In addition, the embodiment of the invention also provides a composition which comprises 0.5-1.5 parts of astragalus and 0.5-3 parts of arrowroot by weight.

It is understood that the composition provided in this example can be the same as the composition described in any of the preceding examples, and is not described in detail.

The features and properties of the present invention are described in further detail below with reference to examples.

Materials: the following examples used Astragalus membranaceus, dried root of Astragalus membranaceus (Fisch.) Bge. of Leguminosae Astragalus membranaceus (Bge.) Hsiao; the arrowroot (Maranta arundinacea L.) used belongs to the tuberous root of arrowroot of the family Arundinaceae (Mrantaceae).

Example 1

A composition for preventing and treating hyperuricemia comprises, by weight, 1 part of radix astragali extract and 1 part of arrowroot powder.

1. A method for preparing radix astragali extract is provided.

Soaking radix astragali in eight times of water for more than 30min, decocting for 2 hr, filtering to separate residue from medicinal liquid, adding 6 times of water into residue, and decocting for 2 hr. Mixing the two filtrates, concentrating to a certain volume, and drying to obtain radix astragali extract.

2. A preparation method of arrowroot powder.

Cleaning fresh arrowroot, peeling, putting the cleaned and peeled fresh arrowroot into a grinder, adding 1.5 times (in other embodiments, 1-2 times) of the volume of the pulp of the arrowroot soaked in water, and filtering by using gauze to obtain mixed water liquid containing arrowroot powder. And (3) containing the arrowroot powder liquid in an open container, standing at room temperature overnight, pouring out the water layer part after water is separated from the precipitate, and leaving the arrowroot powder precipitate. And (4) filling the precipitate into a larger open container, and naturally airing at room temperature or drying at low temperature to obtain the arrowroot powder.

3. And (3) compounding the composition.

Mixing the radix astragali extract and arrowroot powder, adding boiling water, rapidly stirring, and adding 20-100ml water per 1g of the mixture to obtain a mixed solution of radix astragali and arrowroot.

The experimental materials, animal and cell sources used in the following examples are as follows:

(1) sources of experimental materials: the Chinese medicinal decoction pieces radix astragali is purchased from Chinese medicinal drink factories of Guangdong province medicinal material company. Potassium Oxonate (97%), allopurinol, Xanthine (XO) were purchased from Sigma chemical company, USA. Xanthine Oxidase (XOD), Creatinine (CRE), urea nitrogen (BUN), Uric Acid (UA) and alanine Aminotransferase (ALT) kits were purchased from Nanjing institute of bioengineering.

(2) Animal origin and feeding: kunming mice (male, 18-22g) were purchased from the laboratory animal center, university of traditional Chinese medicine, Guangzhou. The animal is bred under the condition of specific Special Pathogen Free (SPF), the temperature is maintained at 20-25 ℃, the light and the dark are alternated for 12h, the relative humidity is 50% -80%, and the animal is strictly bred by using sterilized water and standard food. The study was conducted and approved by the animal ethics committee of the university of traditional Chinese medicine, Guangzhou.

Example 2

And (5) animal experiments.

Grouping experiments, modeling and dosing:

60C 57BL/6J mice (male, 18-22g) were taken, after adaptive feeding for 7 days, a blank group of 10 mice was injected with 0.5% CMC-Na solvent (0.2mL/10g), and the other mice were treated with oteracil potassium(PO)300mg·kg ^-1 (i.p) establishing a hyperuricemia model, using 0.5 percent of sodium carboxymethyl cellulose (CMC-Na) as a solvent, and carrying out intraperitoneal injection on the mice for 14 days to make the model.

After the model was successfully formed 14 days later, the mice were randomly assigned to a model group, an Allopurine (ALL) alcohol positive group (5 mg. kg) by the numerical method ^-1 ) The high, medium and low dose groups of astragalus (RA) + arrowroot (ZY), the normal dose group of arrowroot and the normal dose group of astragalus are 6 groups, and each group contains 10. Each group was given with normal feed, pure water, free diet. All mice were given a normal diet. Allopurinol positive group, arrowroot and astragalus root high-medium and low-dose group are administrated 1 time (0.1mL/10g) each day, and are continuously infused for 14 days, and the blank group and the model group are infused with equal volume of distilled water. Specific groups and administrations are shown in table 1.

TABLE 1 grouping and dosing amounts

Material taking: after 28 days of administration, fasting was carried out for 24h after the last administration, and after 24h of advance, all animals were deprived of feed, but drinking water was normally supplied, and the weight was determined. The animals were anesthetized, blood was collected from the venous plexus basidiophorus of the mouse after anesthesia, then blood samples of the mice were taken in a 2ml lep tube, centrifuged (3000rpm,4 ℃) for 10min, and the upper serum was extracted, placed in an EP tube, and stored in a low-temperature refrigerator at-80 ℃. The kidney and the liver were quickly taken out on an ice bench and stored in 4% paraformaldehyde solution and a low temperature freezer at-80 ℃. And (5) precisely weighing, and calculating the mass of the liver, the spleen and the kidney and the organ coefficient.

General biochemical assays (UA, CRE, BUN, XOD, ALT): the serum levels of Uric Acid (UA), Xanthine Oxidase (XOD), alanine Aminotransferase (ALT), Creatinine (CRE) and urea nitrogen (BUN) were determined in each group of mice according to the kit protocol.

Experimental groups mice were shown in Table 2 above for blood Uric Acid (UA), Creatinine (CRE), urea nitrogen (BUN) and Xanthine Oxidase (XOD) concentrations.

TABLE 2 results of the experiment

Note: the results are expressed as mean ± standard deviation and, compared to the model set, ^** P<0.01, ^* P<0.05; in comparison with the normal group, ^## P<0.01， ^# P<0.05。

compared with the normal group, the concentrations of UA, CRE, BUN, XOD and ALT in the serum of the model group are obviously increased (P <0.05), which indicates that the model building is successful. The blood uric acid concentration of mice given the allopurinol group and the traditional Chinese medicine composition group is obviously reduced compared with that of a model group, which shows that the traditional Chinese medicine composition can reduce the blood uric acid concentration of the hyperuricemia model mice; the concentration of CRE, BUN, XOD and ALT in the serum of mice given the traditional Chinese medicine composition is obviously reduced compared with that of model group (P <0.05), while the reduction of allopurinol is not obvious. The results show that the traditional Chinese medicine composition can reduce the concentration of CRE, BUN, XOD and ALT in serum of a hyperuricemia model mouse, has the effects of treating and protecting liver and kidney of the hyperuricemia model mouse, belongs to the effect of reducing the uric acid level in the hyperuricemia model mouse by multiple indexes, and allopurinol only has the effect of reducing uric acid by a single index, and the results are shown in figures 1-5 and table 2.

Pathological section observation of mouse kidney: the kidney of the mouse was taken out from 4% paraformaldehyde, cut into sections with a thickness of 4 μm to 5 μm, HE-stained, observed under a microscope, and the change of the kidney tissue was observed, HE-stained, and the pathological change of the kidney tissue was observed under an optical microscope (x 200).

Observing the HE slices of the kidney tissues of each group of mice under a common optical microscope, and finding that the kidney tissues of the mice in the blank group have complete structures, full structures of glomeruli and renal tubules, no phenomena of shrinkage, expansion and deformation and no cell swelling; the structural disorder of the kidney tissue of the model group mouse obviously shows that the dilatation of the renal tubule lumen is serious, the cell shedding and nuclear membrane separation of renal tubular epithelial cells occur, and the glomerulus also obviously shrinks; the pathological morphological change of kidney tissues is obviously relieved by the administration of the traditional Chinese medicine composition, glomerulus is not obviously shrunk, the tubular cavity of the renal tubule is not obviously expanded, the epithelial cells of the renal tubule do not obviously fall off and tend to be in a normal shape, the whole structure of the kidney of a mouse is basically recovered to be normal, and the improvement degree is not obvious after the administration of allopurinol. In conclusion, the kidney tissue structure of the mice after the intervention of the traditional Chinese medicine composition group is obviously improved compared with the kidney tissue damage of the model group, and the positive allopurinol has larger damage degree to the kidney, which indicates that the traditional Chinese medicine composition can be taken for a long time, and has a certain protection effect on the kidney while reducing uric acid, and the result is shown in fig. 6.

In the experimental process, the mice of each administration group have normal diet and good growth condition; the model group mice had a poorer diet and a lower weight than the normal group. After the experimental period was over, the liver, kidney and spleen tissues were dissected and weighed, and data was recorded with the results shown in the table: compared with the composition group and the normal group, the weight of the organs of the model group is obviously increased (P is less than 0.05), which indicates that the organ tissues are swelled after the mice are injected with potassium oxonate in the abdominal cavity; while the administration of the positive drug group does not significantly reduce the degree of tissue swelling. The results show that the potassium oxonate-induced organ tissue swelling can be interfered after the Chinese medicinal composition is administered, and the results are shown in table 3.

TABLE 3 weight of organs in each group of mice

Group of	Liver weight (g)	Spleen weight (g)	Bilateral kidney weight (g)
				Control	0.87±0.05 ^#	0.10±0.0058 ^*	0.22±0.013 ^*
Model	0.99±0.044 ^#	0.11±0.0073 ^#	0.24±0.016 ^#
				ALL	0.93±0.025	0.11±0.0047	0.24±0.0096
H	0.86±0.046 ^**	0.096±0.096 ^**	0.21±0.010 ^**
				M	0.90±0.057	0.097±0.0047 ^**	0.21±0.010 ^**
L	0.90±0.065	0.10±0.0083 ^*	0.22±0.016 ^*

the kidney index of the model group mice is 11.33 +/-0.61, which is obviously higher than that of the blank group mice by 9.72 +/-0.84, and the difference of the two groups has statistical significance (P < 0.05). The kidney indexes of mice in high, medium and low dose groups of the traditional Chinese medicine composition are lower than those of a hyperuricemia model group, and the statistical analysis shows that the difference has statistical significance (P is less than 0.05), so that the administration group has a certain inhibition effect on kidney enlargement caused by oteracil potassium. The results are shown in Table 4.

TABLE 4 organ index of mice in each group

Group of	Liver index	Spleen index	Renal index
				Control	41.76±2.27 ^**	4.42±0.38 ^**	9.72±0.84 ^**
Model	47.47±4.59 ^##	5.15±0.28 ^##	11.33±0.61 ^##
				ALL	44.39±2.68	5.39±0.47	11.33±0.98
H	40.43±3.01 ^**	4.62±0.13 ^*	10.15±0.29 ^*
				M	43.43±2.65 ^*	4.55±0.26 ^**	10.00±0.56 ^**
L	42.13±4.25 ^*	4.72±0.43 ^*	10.38±0.95 ^*

Note: the results are expressed as mean ± standard deviation and, compared to the model set, ^** P<0.01, ^* P<0.05; in comparison with the normal group, ^## P<0.01, ^# P<0.05。

the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The application of the composition in the medicines for preventing and treating hyperuricemia is characterized in that the composition comprises the following components in parts by weight: 0.5-1.5 parts of astragalus and 0.5-3 parts of arrowroot.

2. The use according to claim 1, wherein the composition comprises, in parts by weight: 0.5-1.5 parts of astragalus and 0.5-1.5 parts of arrowroot.

3. The use of claim 1, wherein the astragalus membranaceus is an astragalus membranaceus extract;

preferably, the extraction method of the astragalus extract comprises the following steps: decocting radix astragali in water, filtering, collecting filtrate, and drying to obtain radix astragali extract;

preferably, the mixing volume ratio of the astragalus root to the water is 1: (6-8);

preferably, the decocting time is 1-3 h;

4. The use of claim 1, wherein the arrowroot comprises arrowroot flour;

5. The use according to any one of claims 1 to 4, wherein the composition further comprises water;

preferably, the water is added in an amount of: adding 20-100ml of water into the mixture of 1g of astragalus and arrowroot.

6. Use of a composition in a medicament for the protection of the liver and kidney, wherein the composition is a composition for use according to any one of claims 1 to 5.

7. Use of a composition in a medicament for the prevention and treatment of hyperuricemia and the protection of the liver and kidney, wherein the composition is the use according to any one of claims 1 to 5.

8. The composition is characterized by comprising 0.5-1.5 parts of astragalus and 0.5-3 parts of arrowroot by weight.

9. The composition of claim 8, wherein the composition comprises 0.5 to 1.5 parts of astragalus and 0.5 to 1.5 parts of arrowroot;

preferably, the astragalus is an astragalus extract;

preferably, the decocting time is 1-3 h;

preferably, the extraction method further comprises decocting the decocted residue with water at least once, mixing the filtrate obtained after decocting and filtering with the previous filtrate, and drying to obtain the radix astragali extract;

preferably, the arrowroot comprises arrowroot powder;

10. The composition of claim 8 or 9, wherein the composition further comprises water;

preferably, the water is added in an amount of: adding 20-100ml of water into the mixture of every 1g of astragalus and arrowroot.