CN111467441A

CN111467441A - Pharmaceutical composition for preventing and treating gout, preparation and application

Info

Publication number: CN111467441A
Application number: CN202010461163.5A
Authority: CN
Inventors: 蔡璐; 马悦然
Original assignee: Individual
Current assignee: Individual
Priority date: 2020-05-27
Filing date: 2020-05-27
Publication date: 2020-07-31

Abstract

The invention discloses a pharmaceutical composition for preventing and treating gout, a preparation and an application thereof, wherein the pharmaceutical composition is prepared from oriental wormwood, lalang grass rhizome, giant knotweed rhizome, clematis root, kudzu vine root, gerbera, polyporus, cortex acanthopanacis, Chinese angelica, paniculate swallowwort root, divaricate saposhnikovia root, willow branch, tetrandra root, notopterygium root, lycopodium clavatum, radix angelicae pubescentis, rhizoma atractylodis stir-fried with bran, lignum pini, liquorice, pseudo-ginseng, snake slough, ground beetle, loofah sponge and the like as raw materials, and can be used for preventing and treating gout, reducing uric acid.

Description

Pharmaceutical composition for preventing and treating gout, preparation and application

Technical Field

The invention relates to a traditional Chinese medicine composition, and in particular relates to a medicine composition for preventing and treating gout, a preparation and application. Belongs to the technical field of traditional Chinese medicines.

Background

Gout is a common and complex type of arthritis, which can be suffered by all ages, with higher incidence in men than women. Patients with gout often have sudden joint pain at night, the joint is in urgent attack, severe pain, edema, red swelling and inflammation appear at the joint, and the pain is slowly relieved until the pain disappears for days or weeks. The most frequently encountered joints are big toes, but the encountered joints are not limited thereto, and are also commonly found in joints of hands, knees, elbows, and the like. The affected joints are red, swollen and inflamed finally, tissues become soft after edema, activities are limited, and daily life is affected finally.

Gout is a crystal-related arthropathy caused by deposition of mono-natriuretic urate, is directly related to hyperuricemia caused by purine metabolic disorder and/or reduction of uric acid excretion, and belongs to the category of metabolic rheumatism. Gout can be complicated with kidney disease, and severe cases can cause joint destruction and renal function damage, often accompanied with hyperlipidemia, hypertension, diabetes, arteriosclerosis, coronary heart disease, etc.

As a chronic crystalline arthritis, gout, hyperuricemia is the basis for gout development. Hyperuricemia and hyperuricemia in urine, which results in the deposition of urate into the lumen or interstitium of the renal tubules, leading to an acute inflammatory response.

The medicines for treating gout mainly comprise non-steroidal anti-inflammatory drugs and glucocorticoids, but generally have large side effects, and after the medicines are stopped, gout attacks repeatedly and finally develops into more harmful chronic inflammation, so that the gout is more difficult to cure, and long-term pain is brought to patients. The gout treatment by using the traditional Chinese medicine can avoid the side effect of the existing medicine, and has great application prospect.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides a pharmaceutical composition, a preparation and application for preventing and treating gout.

In order to achieve the purpose, the invention adopts the following technical scheme:

1. a pharmaceutical composition for preventing and treating gout comprises the following raw materials in parts by weight: 0.1-30 parts of oriental wormwood, 0.1-35 parts of cogongrass rhizome, 0.1-35 parts of giant knotweed, 0.1-35 parts of clematis root, 0.1-40 parts of kudzu root, 0.1-25 parts of gerbera pilosula, 0.1-35 parts of polyporus umbellatus, 0.1-30 parts of cortex acanthopanacis, 0.1-50 parts of angelica, 0.1-50 parts of paniculate swallowwort root, 0.1-30 parts of divaricate saposhnikovia root, 0.1-45 parts of willow twig, 0.1-35 parts of radix stephaniae tetrandrae, 0.1-45 parts of notopterygium root, 0.1-35 parts of lycopodium clavatum, 0.1-40 parts of radix angelicae pubescentis, 0.1-35 parts of bran-fried rhizoma atractylodis, 0.1-40 parts of Chinese pine nodular branch, 0.1-35 parts of liquorice, 0.1-30 parts of pseudo-ginseng, 0.1-15 parts of snake slough.

2. A preparation for preventing and treating gout comprises the pharmaceutical composition.

Preferably, the formulation is in the form of mixture, capsule, tablet, powder, paste, granule, syrup or pill.

3. The preparation method of the preparation comprises the steps of mixing the raw materials according to the formula amount, decocting with water, extracting to obtain an extract, and preparing the preparation according to a conventional method of a pharmaceutical preparation.

Preferably, the specific method for water decoction extraction is as follows: the preparation method comprises the steps of firstly crushing the raw materials according to the formula ratio, putting the crushed raw materials into an extraction tank, adding water, decocting for two times, namely 2 hours for the first time and 1.5 hours for the second time, filtering, combining extracting solutions, concentrating the filtrate into clear paste with the relative density of 1.15-1.20 (65 ℃), drying and crushing to obtain the extract.

Preferably, the water consumption is 5-8 times of the total weight of the raw materials in each decoction, and more preferably 6 times, and the raw materials are soaked in water for 10 hours before the first decoction.

Further preferably, the vacuum degree of the filtrate concentration is 0.4 to 0.6 kPa.

Further preferably, vacuum continuous belt drying is adopted, and the specific process conditions are as follows: the vacuum degree is 950-1000 Pa, the first-stage temperature is 75 ℃, the second-stage temperature is 70 ℃, the third-stage temperature is 70 ℃, and the drying time is 2 hours.

Preferably, the extract is coated before being prepared into a preparation, and the specific method comprises the following steps in parts by weight:

(A) adding 3-5 parts of hydroxyethyl cellulose and 6-8 parts of polyaspartic acid into 20-25 parts of water, and stirring until the materials are completely dissolved to obtain a premixed solution;

(B) then adding 1 part of extract into the premixed solution, carrying out ultrasonic oscillation and drying to obtain a pre-clathrate compound;

(C) and finally, adding the pre-inclusion compound into 18-20 parts of silkworm silk fibroin-chitosan oligosaccharide mixed solution with the pH = 6-7, standing and drying to obtain the coated extract.

Further preferably, in the step (B), the process conditions of the ultrasonic oscillation are: ultrasonic oscillation at 300-500W for 40-60 minutes.

Further preferably, in the step (C), the preparation method of the bombyx mori silk fibroin-chitosan oligosaccharide mixed solution is as follows: firstly, degumming 1 part by weight of silkworm silk, then hydrolyzing, then adding 0.08-0.1 part by weight of chitosan oligosaccharide, and carrying out ultrasonic oscillation until the chitosan oligosaccharide is completely dissolved to obtain the mixed solution.

More preferably, the degumming treatment is carried out by the following specific methods: soaking silkworm silk in a sodium carbonate aqueous solution with the mass concentration of 0.05-0.1% and the weight of 4-6 times of that of the silkworm silk, boiling for 30-40 minutes while stirring, repeating for 3-4 times, taking out, and washing with deionized water for 2-3 times.

Still more preferably, the specific method of hydrolysis is: soaking the degummed silkworm silk in a potassium chloride solution with the mass concentration of 1-1.2% and the weight of 3-5 times of that of the silkworm silk, and treating for 2-3 hours at the temperature of 130-140 ℃ and under the pressure of 0.5-0.6 MPa.

Further preferably, in the step (C), the standing time is 3 to 5 hours.

Preferably, the preparation is a mixture and is prepared by dissolving hydroxypropyl- β -cyclodextrin in water, adding the extract, stirring at 30-40 ℃ for 50-80 minutes, filtering until the clarity is qualified, filling, sterilizing and packaging, wherein the mass ratio of the extract to the hydroxypropyl- β -cyclodextrin to the water is 1: 3-5: 100.

Preferably, the preparation is a capsule, and the specific preparation method is as follows: mixing the extract with dextrin, granulating, drying, grading, adding calcium hydrogen phosphate dihydrate, sodium carboxymethyl starch and magnesium stearate, mixing, filling into capsule (hollow capsule shell is available from Suzhou capsule Co., Ltd., model No. 0), and packaging to obtain the capsule; the mass ratio of the extract to dextrin, calcium hydrophosphate dihydrate, sodium carboxymethyl starch and magnesium stearate is 1: 5-7: 22-30: 8-10: 12 to 15.

Preferably, the preparation is a tablet, and the preparation method comprises the steps of mixing the extract with microcrystalline cellulose, dicalcium phosphate, crospovidone, sodium carboxymethylcellulose and an adhesive, granulating, drying, grading, adding magnesium stearate and colloidal silicon dioxide, mixing, tabletting and packaging to obtain the tablet, wherein the mass ratio of the extract to the microcrystalline cellulose to the dicalcium phosphate, the crospovidone, the sodium carboxymethylcellulose, the adhesive to the magnesium stearate and the colloidal silicon dioxide is 1: 8-10: 6-8: 5-7: 5-8: 2-3: 3-5: 5-8, the adhesive is prepared by adding povidone K30 into absolute ethyl alcohol to be fully dissolved, and the mass-volume ratio of the povidone K30 to the absolute ethyl alcohol is 1 g: 10-15 m L.

Preferably, the preparation is powder, and the specific preparation method comprises the following steps: pulverizing the extract into 150 mesh, and packaging (2 g per bag).

Preferably, the preparation is an ointment, and the specific preparation method is as follows: and adding the extract into honey refined by 2-3 times, uniformly stirring, sterilizing and filling to obtain the honey beverage.

Preferably, the preparation is granules, and the specific preparation method is as follows: firstly, mixing the extract with dextrin according to the mass ratio of 1: 3-4, mixing and granulating, wherein the particle size is 500-800 mu m, then drying for 12 hours at 65 ℃ in a fluidized bed, sieving, grading, and subpackaging (10 g per bag) to obtain the granules.

Preferably, the preparation is syrup, and the preparation method comprises the following steps: dissolving sucrose in water, adding the extract, stirring, filtering, sterilizing, and packaging; the mass ratio of the extract to the sucrose to the water is 1: 1.2-1.5: 2 to 3.

Preferably, the preparation is a pill, and the specific preparation method comprises the following steps: the extract and honey which is 2-3 times of the extract are stirred and mixed uniformly, the mixture is placed in a stainless steel sugar coating machine, the sugar coating machine is started to form pills, the pills are dried and packaged, and the pills are obtained, wherein the particle size of the pills is 2-2.5 cm.

4. The application of the pharmaceutical composition or the preparation in preparing gout treatment medicines.

The pharmacological effects of the raw materials are explained below:

herba artemisiae scopariae is bitter and pungent in taste and slightly cold in nature, has the effects of clearing away damp-heat, promoting bile flow and removing jaundice, and has the main functions: jaundice, oliguria, damp warmth, summer dampness, eczema and pruritus.

Cogongrass rhizome, sweet and cold, has the efficacies of cooling blood and stopping bleeding, clearing heat and promoting urination, and has the main functions: hematemesis due to blood heat, epistaxis, hematuria, fever with polydipsia, cough due to lung heat, stomach heat vomiting, jaundice due to damp-heat, edema with scanty urine, stranguria with astringents due to heat.

Giant knotweed rhizome is slightly bitter and cold, has the effects of dispelling wind and promoting diuresis, removing blood stasis and relieving pain, relieving cough and reducing sputum, and has the main functions: can be used for treating arthralgia, jaundice due to damp-heat pathogen, amenorrhea, abdominal mass, scald due to hot water or fire, traumatic injury, carbuncle, swelling, sore, and cough with excessive phlegm.

The clematis root, pungent and salty in flavor and warm in nature, has the effects of expelling wind-damp and dredging the channels and collaterals, and has the main functions: wind-damp arthralgia, numbness of limbs, spasm of tendons and vessels, and difficulty in flexion and extension.

Kudzu vine root, sweet and pungent in taste and cool in nature, has the effects of expelling pathogenic factors from muscles and skin, allaying fever, promoting eruption, promoting the production of body fluid to quench thirst, invigorating yang and relieving diarrhea, and has the main functions: exterior syndrome with fever, pain of neck and back, measles without adequate eruption, thirst due to fever, diabetes due to yin deficiency, dysentery due to heat-purging, and diarrhea due to spleen deficiency.

Geranium wilfordii, bitter, slightly pungent and mild, has the main functions: dispel rheumatism. Can be used for treating rheumatic arthralgia.

Polyporus umbellatus has sweet, bland and mild taste, and has the effects of promoting diuresis and eliminating dampness. It is indicated for dysuria, edema, diarrhea, stranguria with turbid urine and leukorrhagia.

Cortex acanthopanacis is pungent and bitter in taste and warm in nature, has the effects of dispelling wind-damp, tonifying liver and kidney, strengthening tendons and bones, inducing diuresis and relieving swelling, and has the main functions: rheumatism, flaccidity of bones and muscles, retardation of children, asthenia, edema and beriberi.

The angelica has sweet and pungent taste and warm nature, has the efficacies of enriching blood and activating blood, regulating menstruation and relieving pain, and relaxing bowel, and has the main functions: blood deficiency and sallow complexion, vertigo and palpitation, irregular menstruation, amenorrhea and dysmenorrhea, deficiency cold and abdominal pain, rheumatic arthralgia, traumatic injury, carbuncle, ulcer, intestinal dryness and constipation. The wine angelica sinensis can activate blood and promote menstruation. Can be used for treating amenorrhea, dysmenorrhea, rheumatalgia, and traumatic injury.

The paniculate swallowwort root is pungent and warm, has the effects of dispelling wind, eliminating dampness, relieving pain and itching, and has the main functions: rheumatic arthralgia, stomach ache and fullness, toothache, lumbago, traumatic injury, rubella and eczema.

Ledebouriella root, pungent and sweet in flavor, slightly warm in nature, with the functions of dispelling wind, relieving exterior syndrome, eliminating dampness, relieving pain and relieving spasm, mainly treating: can be used for treating exterior syndrome due to exogenous pathogenic factor, rubella pruritus, rheumatalgia, tetanus, and spleen deficiency with excessive dampness.

Willow branch, bitter and cold in property, has the main indications: dispel wind, induce diuresis, alleviate pain, and alleviate edema. It can be used for treating rheumatic arthralgia, gonorrhea, whitish and turbid urine, urinary obstruction, infectious hepatitis, wind swelling, furuncle, erysipelas, dental caries, and gingival swelling.

Stephania tetrandra, pungent and bitter in taste and cold in nature, has the effects of dispelling wind and relieving pain, inducing diuresis and relieving swelling, and has the main functions: rheumatic arthralgia, edema, beriberi, dysuria, eczema and sore.

Notopterygium root, pungent and bitter in flavor, warm in nature, and mainly used for relieving exterior syndrome, dispelling cold, expelling wind, eliminating dampness and relieving pain, and has the following functions: wind-cold type common cold, wind-cold-dampness arthralgia, stiff neck, spasm of tendons and tendons, soreness and pain of joints, edema due to wind-damp, superficial infection and sore-toxin.

Herba lycopodii, bitter and slightly pungent in taste, warm in nature, and has the effects of dispelling wind and removing dampness, relaxing tendons and activating collaterals, and the main functions are as follows: soreness and pain in joints, difficulty in flexion and extension.

The pubescent angelica is pungent and bitter in taste and slightly warm in nature, has the effects of dispelling wind and eliminating dampness and relieving pain and arthralgia, and has the main functions: arthralgia due to wind-cold-dampness, pain in waist and knees, headache due to wind-cold-dampness, shaoyin wind-cold-type headache.

Stir-frying rhizoma atractylodis with bran, pungent, bitter and warm, and mainly functions: dry dampness and invigorate spleen, dispel wind and cold, improve vision. Can be used for treating abdominal distention, diarrhea, edema, rheumatalgia, wind-cold type common cold, and nyctalopia.

The Chinese pine node is bitter and pungent in taste and warm in nature, has the effects of dispelling wind and removing dampness, and dredging collaterals and relieving pain, and has the main functions: wind-cold-dampness arthralgia, spasm and spasm of muscles and tendons, traumatic injury and pain.

Licorice, sweet and neutral, has the main functions: replenishing qi and strengthening the middle warmer; relieving spasm and pain; moistening lung to arrest cough; purging pathogenic fire and removing toxic substances; harmonize the drugs. Mainly lassitude and poor appetite; emaciation and yellow face; palpitation and shortness of breath; abdominal pain and loose stool; limb spasm and pain; irritability; cough and asthma; swollen and sore throat; carbuncle sore and swelling pain; infantile fetal toxicity; and drug and food poisoning.

Pseudo-ginseng, sweet, slightly bitter and warm, has the efficacies of dissipating blood stasis and stopping bleeding, and relieving swelling and pain, and has the main functions: hemoptysis, hematemesis, epistaxis, hematochezia, metrorrhagia and metrostaxis, traumatic hemorrhage, thoracico-abdominal pain, traumatic swelling and pain.

The snake slough is salty and sweet in taste and neutral in nature, has the efficacies of dispelling wind, arresting convulsion, removing nebula and detoxifying, and has the main functions: infantile convulsion, convulsion and spasm, nebula, pharyngitis, sore throat, swelling and skin pruritus.

Ground beetle, salty in taste and cold in nature, has the efficacies of breaking blood and removing stasis, and reuniting tendons and bones, and has the main functions: traumatic injury, injury of tendons and bones, amenorrhea due to blood stasis, postpartum abdominal pain due to blood stasis, and abdominal mass.

The loofah sponge has sweet taste and mild nature, has the effects of dispelling wind, dredging collaterals, promoting blood circulation and promoting lactation, and has the main functions: spasm of arthralgia, distending pain in chest and hypochondrium, obstruction of breast milk, and swelling and pain due to acute mastitis.

The invention has the beneficial effects that:

the traditional Chinese medicine preparation is prepared from raw materials of oriental wormwood, lalang grass rhizome, giant knotweed rhizome, clematis root, kudzuvine root, gerbera, polyporus umbellatus, acanthopanax bark, Chinese angelica, paniculate swallowwort root, divaricate saposhnikovia root, willow branch, tetrandra root, notopterygium root, common clubmoss herb, doubleteeth pubescent angelica root, rhizoma atractylodis stir-fried with bran, nodular branch of Chinese pine, liquorice, pseudo-ginseng, snake slough, ground beeltle, loofah sponge and the like, and can be used for preventing and treating.

Wherein, the oriental wormwood and the lalang grass rhizome are monarch drugs and are mainly used for clearing heat and promoting diuresis of patients, which is the root for controlling gout; polyporus umbellatus and radix Stephaniae Tetrandrae are ministerial drugs and auxiliary monarch drugs play a role in clearing heat; giant knotweed rhizome, clematis root, kudzuvine root, gerbera, cortex acanthopanacis, Chinese angelica, paniculate swallowwort root, divaricate saposhnikovia root, willow twig, fourstamen stephania root, incised notopterygium rhizome, common clubmoss herb, doubleteeth pubescent angelica root, bran-fried rhizoma atractylodis, Chinese pine nodular branch, pseudo-ginseng, snake slough, ground beeltle and loofah sponge are taken as adjuvant drugs, the effect of clearing heat is enhanced by matching with monarch drugs and ministerial drugs, the symptoms of; the liquorice is used as a guiding drug to coordinate the effects of the other drugs in the recipe and direct the drugs to the affected part.

The invention can mix all raw materials according to the formula amount, decoct and extract the raw materials to obtain the extract, and then prepare the preparation according to the conventional method of the pharmaceutical preparation. The extract may also be coated before being prepared into a preparation. According to different clinical requirements, the composition can be prepared into different dosage forms, such as mixture, capsule, tablet, powder, paste, granule, syrup or pill.

The coating treatment is to pre-coat the extract by using a premixed solution of hydroxyethyl cellulose and polyaspartic acid, and then further treat the pre-coated substance by using a silkworm silk fibroin-chitosan oligosaccharide mixed solution. Most of the raw materials of the invention are cold-natured traditional Chinese medicines or have bitter taste, on one hand, the coating treatment can shield the taste, on the other hand, hydroxyethyl cellulose, polyaspartic acid, silkworm fibroin protein, chitosan oligosaccharide and the like used in the coating treatment have good degradation performance in a human body, can be slowly decomposed after entering the human body, play a role in slow release, prolong the effective time of the medicine and avoid the side effect in the aspect of gastrointestinal tract caused by the release of a large amount of cold-natured effective components.

During pre-inclusion, polyhydroxycellulose and polyaspartic acid are introduced, the polyhydroxycellulose contains a large number of hydroxyl groups, the polyaspartic acid contains a large number of imino groups, and hydrogen bonds are formed between the hydroxyl groups and the imino groups to construct a net structure and effectively include the extract. When the silkworm silk fibroin-chitosan oligosaccharide mixed solution is used for treating the pre-inclusion compound, as chitosan oligosaccharide has positive charge, the isoelectric point of silkworm silk fibroin is about 3.6, when the pH of a control system is = 6-7, silkworm silk fibroin has negative charge, the electrostatic action of the silkworm silk fibroin and the chitosan oligosaccharide promotes the formation of a core-shell structure on the surface of the pre-inclusion compound, so that further inclusion is realized, and amino and hydroxyl contained in the silkworm silk fibroin and hydroxyl contained in the chitosan oligosaccharide can also form hydrogen bond action to form a porous surface structure, so that the slow release effect is further improved.

Detailed Description

The present invention will be further illustrated by the following examples, which are intended to be merely illustrative and not limitative.

For convenience of comparison, the formulation formulations prepared in examples and comparative examples are all granules, but the formulation formulations of the present application are not limited to only granules.

Example 1:

a preparation for preventing and treating gout comprises the following raw materials: 0.1kg of oriental wormwood, 35kg of lalang grass rhizome, 0.1kg of giant knotweed rhizome, 35kg of clematis root, 0.1kg of kudzuvine root, 25kg of hairyvein agrimony, 0.1kg of polyporus umbellatus, 30kg of cortex acanthopanacis, 0.1kg of Chinese angelica, 50kg of paniculate swallowwort root, 0.1kg of divaricate saposhnikovia root, 45kg of willow branch, 0.1kg of tetrandra root, 45kg of notopterygium root, 0.1kg of common clubmoss herb, 40kg of pubescent angelica root, 0.1kg of rhizoma atractylodis stir-fried with bran, 40kg of Chinese pine nodular branch, 0.1kg of liquorice, 30kg of pseudo-ginseng, 0..

The preparation method of the preparation comprises the steps of mixing the raw materials according to the formula amount, decocting with water, extracting to obtain an extract, and preparing the preparation according to a conventional method of a pharmaceutical preparation.

The specific method for water decoction extraction is as follows: the preparation method comprises the steps of firstly crushing the raw materials according to the formula ratio, putting the crushed raw materials into an extraction tank, adding water, decocting for two times, namely 2 hours for the first time and 1.5 hours for the second time, filtering, combining extracting solutions, concentrating the filtrate into clear paste with the relative density of 1.20 (65 ℃), drying and crushing to obtain the extract. The water consumption is 5 times of the total weight of the raw materials in each decoction, and the raw materials are soaked in water for 10 hours before the first decoction. The vacuum degree of the filtrate was 0.6 kPa. Vacuum continuous belt type drying is adopted, and the specific process conditions are as follows: the vacuum degree is 950Pa, the first stage temperature is 75 ℃, the second stage temperature is 70 ℃, the third stage temperature is 70 ℃, and the drying time is 2 hours.

The preparation is granules, and the preparation method comprises the following steps: firstly, mixing the extract with dextrin according to the mass ratio of 1: 4 mixing and granulating, the particle size is required to be 500 μm, then drying for 12 hours at 65 ℃ in a fluidized bed, sieving, grading, and subpackaging (10 g per bag) to obtain the granules.

Example 2:

a preparation for preventing and treating gout comprises the following raw materials: 30kg of oriental wormwood, 0.1kg of lalang grass rhizome, 35kg of giant knotweed rhizome, 0.1kg of clematis root, 40kg of kudzuvine root, 0.1kg of hairyvein agrimony, 35kg of polyporus umbellatus, 0.1kg of cortex acanthopanacis, 50kg of Chinese angelica, 0.1kg of paniculate swallowwort root, 30kg of divaricate saposhnikovia root, 0.1kg of willow branch, 35kg of tetrandra root, 0.1kg of notopterygium root, 35kg of common clubmoss herb, 0.1kg of pubescent angelica root, 35kg of rhizoma atractylodis stir-fried with bran, 0.1kg of Chinese pine nodular branch, 35kg of liquorice, 0.1kg of pseudo-ginseng.

The specific method for water decoction extraction is as follows: the preparation method comprises the steps of firstly crushing the raw materials according to the formula ratio, putting the crushed raw materials into an extraction tank, adding water, decocting for two times, namely 2 hours for the first time and 1.5 hours for the second time, filtering, combining extracting solutions, concentrating the filtrate into clear paste with the relative density of 1.15 (65 ℃), drying and crushing to obtain the extract. The water consumption is 8 times of the total weight of the raw materials in each decoction, and the raw materials are soaked in water for 10 hours before the first decoction. The vacuum degree of the filtrate was 0.4 kPa. Vacuum continuous belt type drying is adopted, and the specific process conditions are as follows: the vacuum degree is 1000Pa, the first stage temperature is 75 ℃, the second stage temperature is 70 ℃, the third stage temperature is 70 ℃, and the drying time is 2 hours.

The preparation is granules, and the preparation method comprises the following steps: firstly, mixing the extract with dextrin according to the mass ratio of 1: 3 mixing and granulating, the grain size is required to be 800 μm, then drying for 12 hours at 65 ℃ in a fluidized bed, sieving, grading, and subpackaging (10 g per bag) to obtain the granules.

Example 3:

The extract is coated before being prepared into a preparation, and the specific method comprises the following steps:

(A) firstly, adding 5kg of hydroxyethyl cellulose and 6kg of polyaspartic acid into 25kg of water, and stirring until the hydroxyethyl cellulose and the polyaspartic acid are completely dissolved to obtain a premixed solution;

(B) then adding 1kg of extract into the premixed solution, carrying out ultrasonic oscillation and drying to obtain a pre-clathrate compound;

(C) and finally, adding the pre-clathrate compound into 18kg of silkworm silk fibroin-chitosan oligosaccharide mixed solution with the pH =7, standing and drying to obtain the coated extract.

In the step (B), the process conditions of ultrasonic oscillation are as follows: the ultrasonic wave was oscillated at 300W for 60 minutes.

In the step (C), the preparation method of the silkworm silk fibroin-chitosan oligosaccharide mixed solution comprises the following steps: firstly, 1kg of silkworm silk is degummed, then is hydrolyzed, then 0.08kg of chitosan oligosaccharide is added, and the mixture is obtained after ultrasonic oscillation until the chitosan oligosaccharide is completely dissolved. The degumming treatment method comprises the following specific steps: soaking silkworm silk in 6 times of 0.05% sodium carbonate aqueous solution by weight, boiling for 40 minutes while stirring, repeating for 3 times, taking out, and washing with deionized water for 3 times. The specific method of hydrolysis is as follows: and soaking the degummed silkworm silk in a potassium chloride solution with the mass concentration of 1.2% and the weight of 3 times of that of the silkworm silk, and treating for 2 hours at the temperature of 130 ℃ and under the pressure of 0.6 MPa.

In the step (C), the standing time was 5 hours.

Example 4:

(A) adding 3kg of hydroxyethyl cellulose and 8kg of polyaspartic acid into 20kg of water, and stirring until the hydroxyethyl cellulose and the polyaspartic acid are completely dissolved to obtain a premixed solution;

(C) and finally, adding the pre-clathrate compound into 20kg of silkworm silk fibroin-chitosan oligosaccharide mixed solution with the pH =6, standing and drying to obtain the coated extract.

In the step (B), the process conditions of ultrasonic oscillation are as follows: 500W ultrasonic oscillation was carried out for 40 minutes.

In the step (C), the preparation method of the silkworm silk fibroin-chitosan oligosaccharide mixed solution comprises the following steps: firstly, 1kg of silkworm silk is degummed, then hydrolyzed, then 0.1kg of chitosan oligosaccharide is added, and the mixture is obtained after ultrasonic oscillation until the chitosan oligosaccharide is completely dissolved. The degumming treatment method comprises the following specific steps: soaking silkworm silk in 4 times of 0.1% sodium carbonate aqueous solution by weight, boiling for 30 minutes while stirring, repeating for 4 times, taking out, and washing with deionized water for 2 times. The specific method of hydrolysis is as follows: and soaking the degummed silkworm silk in 5 times of potassium chloride solution with the mass concentration of 1% by weight, and treating for 3 hours at the temperature of 140 ℃ and under the pressure of 0.5 MPa.

In the step (C), the standing time was 3 hours.

Example 5:

a preparation for preventing and treating gout comprises the following raw materials: 28kg of oriental wormwood, 27kg of lalang grass rhizome, 13kg of giant knotweed rhizome, 12kg of clematis root, 12kg of kudzu root, 11kg of hairyvein agrimony, 20kg of polyporus umbellatus, 12kg of cortex acanthopanacis, 11kg of Chinese angelica, 10kg of paniculate swallowwort root, 9kg of divaricate saposhnikovia root, 9kg of willow branch, 20kg of fourstamen stephania root, 8kg of notopterygium root, 8kg of lycopodium clavatum, 7kg of radix angelicae pubescentis, 7kg of bran-fried rhizoma atractylodis, 6kg of Chinese pine nodular branch, 2kg of liquorice, 6kg of pseudo.

The specific method for water decoction extraction is as follows: the preparation method comprises the steps of firstly crushing the raw materials according to the formula ratio, putting the crushed raw materials into an extraction tank, adding water, decocting for two times, namely 2 hours for the first time and 1.5 hours for the second time, filtering, combining extracting solutions, concentrating the filtrate into clear paste with the relative density of 1.18 (65 ℃), drying and crushing to obtain the extract. The water consumption is 6 times of the total weight of the raw materials in each decoction, and the raw materials are soaked in water for 10 hours before the first decoction. The vacuum degree of the filtrate was 0.5 kPa. Vacuum continuous belt type drying is adopted, and the specific process conditions are as follows: the vacuum degree is 980Pa, the first stage temperature is 75 ℃, the second stage temperature is 70 ℃, the third stage temperature is 70 ℃, and the drying time is 2 hours.

The preparation is granules, and the preparation method comprises the following steps: firstly, mixing the extract with dextrin according to the mass ratio of 1: 3.5 mixing and granulating, the grain size is required to be 600 μm, then drying for 12 hours at 65 ℃ in a fluidized bed, sieving, grading and subpackaging (10 g per bag) to obtain the granules.

(A) firstly, adding 4kg of hydroxyethyl cellulose and 7kg of polyaspartic acid into 22kg of water, and stirring until the hydroxyethyl cellulose and the polyaspartic acid are completely dissolved to obtain a premixed solution;

(C) and finally, adding the pre-clathrate compound into 19kg of silkworm silk fibroin-chitosan oligosaccharide mixed solution with the pH =6.5, standing and drying to obtain the coated extract.

In the step (B), the process conditions of ultrasonic oscillation are as follows: the ultrasonic wave of 400W was oscillated for 50 minutes.

In the step (C), the preparation method of the silkworm silk fibroin-chitosan oligosaccharide mixed solution comprises the following steps: firstly, 1kg of silkworm silk is degummed, then is hydrolyzed, then 0.09kg of chitosan oligosaccharide is added, and the mixture is obtained after ultrasonic oscillation until the chitosan oligosaccharide is completely dissolved. The degumming treatment method comprises the following specific steps: soaking silkworm silk in 5 times of 0.08% sodium carbonate aqueous solution by weight, boiling for 35 minutes while stirring, repeating for 3 times, taking out, and washing with deionized water for 3 times. The specific method of hydrolysis is as follows: and soaking the degummed silkworm silk in a potassium chloride solution with the mass concentration of 1.1% and the weight of 4 times of that of the silkworm silk, and treating for 2.5 hours at 135 ℃ and under the pressure of 0.5 MPa.

In the step (C), the standing time was 4 hours.

Example 6:

(B) then adding 1kg of the extract into the premixed solution, and performing ultrasonic oscillation and drying to obtain the composition.

Example 7:

The extract is coated before being prepared into a preparation, and the specific method comprises the following steps: adding 1kg of the extract into 18kg of the silkworm silk fibroin-chitosan oligosaccharide mixed solution with pH =7, standing, and drying to obtain the coated extract.

The preparation method of the silkworm silk fibroin-chitosan oligosaccharide mixed solution comprises the following steps: firstly, 1kg of silkworm silk is degummed, then is hydrolyzed, then 0.08kg of chitosan oligosaccharide is added, and the mixture is obtained after ultrasonic oscillation until the chitosan oligosaccharide is completely dissolved. The degumming treatment method comprises the following specific steps: soaking silkworm silk in 6 times of 0.05% sodium carbonate aqueous solution by weight, boiling for 40 minutes while stirring, repeating for 3 times, taking out, and washing with deionized water for 3 times. The specific method of hydrolysis is as follows: and soaking the degummed silkworm silk in a potassium chloride solution with the mass concentration of 1.2% and the weight of 3 times of that of the silkworm silk, and treating for 2 hours at the temperature of 130 ℃ and under the pressure of 0.6 MPa.

The standing time was 5 hours.

Comparative example 1

A formulation comprising the following raw materials: 35kg of cogongrass rhizome, 0.1kg of giant knotweed rhizome, 35kg of clematis root, 0.1kg of kudzu root, 25kg of gerbera pilosula, 0.1kg of polyporus umbellatus, 30kg of cortex acanthopanacis, 0.1kg of Chinese angelica, 50kg of paniculate swallowwort root, 0.1kg of divaricate saposhnikovia root, 45kg of willow branch, 0.1kg of tetrandra root, 45kg of notopterygium root, 0.1kg of lycopodium clavatum, 40kg of pubescent angelica root, 0.1kg of bran-fried rhizoma atractylodis, 40kg of Chinese pine nodular branch, 0.1kg of liquorice, 30kg of pseudo-ginseng, 0.1kg of snake slough.

The rest is the same as example 1.

Comparative example 2

A formulation comprising the following raw materials: 0.1kg of oriental wormwood, 35kg of lalang grass rhizome, 0.1kg of giant knotweed rhizome, 35kg of clematis root, 0.1kg of kudzuvine root, 25kg of hairyvein agrimony, 30kg of cortex acanthopanacis, 0.1kg of Chinese angelica, 50kg of paniculate swallowwort root, 0.1kg of divaricate saposhnikovia root, 45kg of willow branch, 0.1kg of tetrandra root, 45kg of incised notopterygium rhizome, 0.1kg of common clubmoss herb, 40kg of pubescent angelica root, 0.1kg of bran-fried rhizoma atractylodis, 40kg of Chinese pine node, 0.1kg of liquoric root, 30kg of pseudo-ginseng, 0.1kg of.

The rest is the same as example 1.

Comparative example 3

A formulation comprising the following raw materials: 0.1kg of oriental wormwood, 35kg of lalang grass rhizome, 35kg of clematis root, 0.1kg of kudzu root, 25kg of hairyvein agrimonia herb and bud, 0.1kg of polyporus umbellatus, 30kg of cortex acanthopanacis, 0.1kg of Chinese angelica, 50kg of paniculate swallowwort root, 0.1kg of divaricate saposhnikovia root, 45kg of willow branch, 0.1kg of tetrandra root, 45kg of notopterygium root, 0.1kg of lycopodium clavatum, 40kg of radix angelicae pubescentis, 0.1kg of bran-fried rhizoma atractylodis, 40kg of Chinese pine nodular branch, 0.1kg of liquorice, 30kg of pseudo-ginseng, 0.1kg of.

The rest is the same as example 1.

Test examples

Taking 240 male mice (BA L B/c mice, (20 +/-2) g) and randomly dividing into 12 groups, 20 mice in each group, dissolving the granules obtained in examples 1-7 or comparative examples 1-3 by distilled water to obtain liquid medicine, wherein the dosage of the distilled water is 5 times of that of the granules, wherein two groups are used as a control group and a positive group, the mice are perfused with gastric physiological saline or 0.25mg/ml allopurinol solution at 8 am every day, the rest 10 groups are separately perfused with the liquid medicine obtained at 8 am every day for 14 days, the administration volume is calculated according to the weight of the mice before each administration (the perfusion dosage is 0.2ml/10 g), 1 day before the last administration, each group of mice is injected with potassium oxonate 250 mg/kg. in the abdominal cavity, blood is collected from the tail vein, the mice are placed for 1 hour at room temperature and then centrifuged for 10min at 3000r/min, serum is taken, the blood uric acid value is measured by a uric acid kit (phosphotungstic acid method), and the blood uric acid value is detected again after the mice are stopped for 1 month.

And measuring the levels of serum urea nitrogen (BUN) and creatinine by using a urea kit, a creatinine kit and an RT-9600 semi-automatic biochemical analyzer.

The results are shown in Table 1.

TABLE 1 mouse results (mean)

	Serum uric acid (mg/L) 1 day after the last administration	Serum uric acid (mg/L) 1 month after stopping drug	Serum urea nitrogen (mmol/L)	Serum creatinine (liver, μmol/L)
					Control group	48.33	50.39	13.67	78.25
Positive group	42.67	58.74	15.55	88.24
					Example 1	38.12	41.06	13.89	78.35
Example 2	38.15	41.07	13.88	78.34
					Example 3	36.01	37.85	13.71	78.29
Example 4	36.02	37.85	13.70	78.28
					Example 5	35.02	36.83	13.70	78.27
Example 6	37.11	38.95	13.73	78.28
					Example 7	37.12	38.94	13.73	78.29
Comparative example 1	41.38	45.75	13.88	78.34
					Comparative example 2	42.07	46.04	13.89	78.36
Comparative example 3	41.44	45.82	13.88	78.35

As can be seen from table 1, compared with the control group, the preparations obtained in examples 1 to 7 can effectively reduce serum uric acid levels, achieve the effect of preventing and treating gout, and are also superior to the positive group, and can control lower serum uric acid levels after the last administration for 1 hour, indicating that sustained release is effective. Moreover, the serum uric acid of the positive group has larger rebound after stopping taking the medicine for 1 month, even higher than that of the control group, which shows that the traditional Chinese medicine preparation has better long-term treatment effect compared with the existing western medicines. Wherein, the raw materials of the examples 3 to 5 are coated before being prepared into the preparation, and the drug effect is better than that of the examples 1 and 2. Example 6 omits the step (C) in the coating treatment, and example 7 only retains the step (C) in the coating treatment, and the serum uric acid lowering effect is slightly worse than that of examples 3 to 5.

The virgate wormwood herb is omitted in the comparative example 1, the polyporus umbellatus is omitted in the comparative example 2, the giant knotweed rhizome is omitted in the comparative example 3, the effect of reducing serum uric acid is obviously poor, and the monarch, minister, assistant and guide relationship of the traditional Chinese medicine composition is destroyed after the omission of individual components, so that the drug effect is influenced.

In addition, compared with the control group, the positive group has slightly increased serum urea nitrogen and serum creatinine, which indicates that the kidney function is damaged to some extent; the indexes of the granules obtained in examples 1 to 7 and comparative examples 1 to 3 are closer to those of serum urea nitrogen and serum creatinine of a control group, which shows that the granules have a protective effect on renal function, and particularly, the coating treatment is performed in examples 3 to 7, and the two indexes are closest to the control group.

Although the present invention has been described with reference to the specific embodiments, it is not intended to limit the scope of the present invention, and various modifications and variations can be made by those skilled in the art without inventive changes based on the technical solution of the present invention.

Claims

1. The pharmaceutical composition for preventing and treating gout is characterized by comprising the following raw materials in parts by weight: 0.1-30 parts of oriental wormwood, 0.1-35 parts of cogongrass rhizome, 0.1-35 parts of giant knotweed, 0.1-35 parts of clematis root, 0.1-40 parts of kudzu root, 0.1-25 parts of gerbera pilosula, 0.1-35 parts of polyporus umbellatus, 0.1-30 parts of cortex acanthopanacis, 0.1-50 parts of angelica, 0.1-50 parts of paniculate swallowwort root, 0.1-30 parts of divaricate saposhnikovia root, 0.1-45 parts of willow twig, 0.1-35 parts of radix stephaniae tetrandrae, 0.1-45 parts of notopterygium root, 0.1-35 parts of lycopodium clavatum, 0.1-40 parts of radix angelicae pubescentis, 0.1-35 parts of bran-fried rhizoma atractylodis, 0.1-40 parts of Chinese pine nodular branch, 0.1-35 parts of liquorice, 0.1-30 parts of pseudo-ginseng, 0.1-15 parts of snake slough.

2. A preparation for preventing and treating gout, comprising the pharmaceutical composition according to claim 1.

3. The preparation of claim 2, wherein the preparation is in a dosage form selected from any one of a mixture, a capsule, a tablet, a powder, a paste, a granule, a syrup and a pill.

4. Use of the pharmaceutical composition of claim 1 or the formulation of claim 2 for the manufacture of a medicament for the treatment of gout.