CN106902295B

CN106902295B - Toxicity-reducing and efficacy-enhancing traditional Chinese medicine tablet for treating gout with syndrome of wind-damp-heat

Info

Publication number: CN106902295B
Application number: CN201710167630.1A
Authority: CN
Inventors: 赵军民
Original assignee: Jiangxi Hongjing Pharmaceutical Co Ltd
Current assignee: Jiangxi Hongjing Pharmaceutical Co., Ltd
Priority date: 2017-03-20
Filing date: 2017-03-20
Publication date: 2020-07-07
Anticipated expiration: 2037-03-20
Also published as: CN106902295A

Abstract

The invention provides an attenuation and synergism traditional Chinese medicine tablet for treating wind-damp heat type gout, which comprises the following raw materials of phellodendron bark, radix stephaniae tetrandrae, rhizoma anemarrhenae, rhizoma atractylodis, rhizoma smilacis glabrae, talc, radix gentianae macrophyllae, rhizoma dioscoreae hypoglaucae, radix cyathulae, rhizoma polygoni cuspidati and raw liquorice. The Chinese medicinal composition combines the attenuation and synergism effects of the tripterygium wilfordii squama for treating the rheumatic fever type gout, combines the traditional Chinese medicine theory understanding of the disease, combines the clinical manifestations of patients, has the effects of clearing heat, drying dampness, promoting diuresis, eliminating turbid pathogen, dredging collaterals and relieving pain through syndrome differentiation, treatment and formula compatibility, has good treatment effect, obviously reduces the toxic and side effects of the tripterygium wilfordii, and is safe and effective when taken at the conventional dosage. The comprehensive evaluation of the invention has good effect of treating the gout, and the clinical popularization should be carried out under the support of experimental evidence.

Description

Toxicity-reducing and efficacy-enhancing traditional Chinese medicine tablet for treating gout with syndrome of wind-damp-heat

The invention relates to the technical field of traditional Chinese medicines, in particular to an attenuation and synergism traditional Chinese medicine tablet for treating rheumatic fever type gout.

Background

Gout is a group of diseases caused by disorders of purine metabolism, overproduction of uric acid or reduced excretion. When the blood uric acid concentration is too high, uric acid crystals are easily formed and deposited on joints, kidneys and other parts, organelles of phagocytes are destroyed, tissues are eroded, immune response is stimulated, and the development of tissue foreign body inflammatory response is caused and accelerated. The disease has high incidence in western countries, and in recent years, with the continuous improvement of the living standard of people in China, the change of life style, the change of high purine, high fat and high protein components in the dietary structure and the annual increase of the incidence of gout, the disease becomes a common clinical disease and a frequently encountered disease. Epidemiological investigations have shown that the prevalence of gout has increased exponentially in countries and regions such as europe, north america, australia, china, etc. since the eighth and ninety years of the last century.

The middle-aged male patients are more, but with the change of life style, the sick population has a trend of younger development; and it has been found that postmenopausal women, and people with obesity, metabolic disease and cardiovascular disease, are at a higher risk of developing gout. Gout patients suffering from other diseases also have certain influence on gout treatment. The gout incidence rate remarkably rises, which seriously affects the physical and mental health and the life quality of people in China and causes wide attention in the medical field.

The treatment of gout includes: medication, diet control, physical therapy, and surgery in severe cases. Oral drug therapy is a common means for treating gout at present. Tripterygium wilfordii has multiple activities of resisting inflammation, resisting tumor, regulating immunity, resisting fertility and the like, is a first choice traditional Chinese medicine for treating autoimmune diseases such as rheumatoid arthritis, glomerulonephritis lupus erythematosus and the like, has quick response and definite curative effect, has irreplaceable effect in clinical application, but has large toxic and side effects, particularly has toxicity to liver which is the first of single medicine to liver injury in related literature reports, is clinically manifested as acute viral hepatitis, and has symptoms of inappetence, hypodynamia, nausea, vomiting, hepatomegaly, elevation of serum alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) and the like, so that the synergy of clinical, pharmaceutical and other disciplines is highly regarded in recent years, and how to treat gout by the Tripterygium wilfordii becomes a research hotspot problem.

The traditional Chinese medicine has long-term medical sources, the traditional Chinese medicine has been used for treating gout for 2000 years, and abundant experience is accumulated for treating gout through a large number of clinical practices. Has certain advantages, diversified treatment means including oral decoction, Chinese patent medicine, acupuncture and moxibustion, external application, fumigation, national medicine and the like, small side effect and definite curative effect, and gradually becomes a current research hotspot.

The invention provides a traditional Chinese medicine tablet for treating wind-heat gout, which is prepared by carrying out special treatment on tripterygium wilfordii, carrying out attenuation and synergism on the tripterygium wilfordii, further reducing the toxicity of the tripterygium wilfordii by adding some compatible traditional Chinese medicine components, and further improving the treatment effect of the tablet on the wind-heat gout by the compatibility of monarch, minister, assistant and guide.

Disclosure of Invention

The toxicity-reducing and efficacy-enhancing traditional Chinese medicine tablet for treating gout with damp-heat wind combines the theoretical understanding of traditional Chinese medicine of the disease, combines the clinical manifestations of patients, has the effects of clearing heat, drying dampness, promoting diuresis, eliminating turbidity, dredging collaterals and relieving pain by dialectical treatment and formula compatibility, has good treatment effect, obviously reduces the toxic and side effects of tripterygium wilfordii, and is safe and effective when taken at the conventional dosage. The comprehensive evaluation of the invention has good effect of treating the gout, and the clinical popularization should be carried out under the support of experimental evidence.

In order to solve the technical problems, the invention provides a toxicity-reducing and synergistic traditional Chinese medicine tablet for treating wind-damp-heat type gout, which comprises auxiliary materials and active ingredients, wherein the active ingredients comprise raw material medicines of tripterygium wilfordii, golden cypress, radix stephaniae tetrandrae, rhizoma anemarrhenae, rhizoma atractylodis, rhizoma smilacis glabrae, talc, radix gentianae macrophyllae, rhizoma dioscoreae hypoglaucae, radix cyathulae, rhizoma polygoni cuspidati and raw liquorice.

Wherein the weight of each raw material medicine in the pharmacodynamic components is 30-40 g of tripterygium wilfordii, 20-30 g of phellodendron amurense, 10-20 g of radix stephaniae tetrandrae, 10-20 g of rhizoma anemarrhenae, 10-20 g of rhizoma atractylodis, 10-20 g of rhizoma smilacis glabrae, 10-20 g of talcum, 10-20 g of gentiana macrophylla, 10-20 g of rhizoma dioscoreae hypoglaucae, 10-20 g of radix cyathulae, 20-30 g of polygonum cuspidatum and 20-30 g of raw liquorice respectively, and the raw material medicines are extracted and prepared into tablets, wherein each tablet is 0.5 g.

Wherein the weight of each raw material medicine in the drug effect components is 30-35 g of tripterygium wilfordii, 25-30 g of phellodendron amurense, 10-15 g of radix stephaniae tetrandrae, 10-15 g of rhizoma anemarrhenae, 10-15 g of rhizoma atractylodis, 10-15 g of rhizoma smilacis glabrae, 10-15 g of talcum, 10-15 g of gentiana macrophylla, 10-15 g of rhizoma dioscoreae septemlobae, 10-15 g of radix cyathulae, 25-30 g of polygonum cuspidatum and 25-30 g of raw liquorice.

Wherein the weight of each raw material medicine in the pharmacodynamic components is respectively 35g of tripterygium wilfordii, 25g of phellodendron amurense, 10g of radix stephaniae tetrandrae, 15g of rhizoma anemarrhenae, 10g of rhizoma atractylodis, 10g of rhizoma smilacis glabrae, 10g of talcum, 15g of gentiana macrophylla, 10g of rhizoma dioscoreae hypoglaucae, 10g of radix cyathulae, 25g of polygonum cuspidatum and 25g of raw liquorice.

The invention also provides a preparation method of the traditional Chinese medicine tablet, which comprises the following steps:

firstly, processing active ingredients of tripterygium wilfordii;

step two, processing the liquorice;

thirdly, processing the rest effective components;

fourthly, preparing the traditional Chinese medicine tablet.

The first step is to uniformly wrap the tripterygium wilfordii with yellow mud, heat the tripterygium wilfordii with microwave, then knock the yellow mud off, brush off loess on the surface, cut up the tripterygium wilfordii, reflux-extract the tripterygium wilfordii with ethanol with the concentration of 70 percent by volume of 10 times and extract the tripterygium wilfordii for 3 times, extract the tripterygium wilfordii for 2 hours each time, combine and concentrate the extract, and evaporate the tripterygium wilfordii to dryness under reduced pressure to obtain the dry powder of the tripterygium wilfordii extract, wherein.

The yellow mud is prepared by uniformly mixing saline water with the mass concentration of 20% and sterile-treated dry loess according to the proportion of 1: 4, and then drying at the low temperature of less than 40 ℃ in a sterile environment to ensure that the water content of the loess is 10% -15%.

Wherein the second step is further to put the liquorice into a superfine pulverizer to be subjected to superfine grinding for 30 minutes to obtain superfine ground powder with more than 400 meshes for later use.

And the third step is further specifically that other raw material medicinal materials are respectively cleaned, crushed and mixed together, water with the mass 6-8 times that of the mixed medicinal material in the step is added, the mixture is boiled with strong fire firstly and then decocted with slow fire for 1 hour, the decoction is filtered, the filter residue is added with water with the mass 4-6 times that of the mixed medicinal material in the step again, the mixture is boiled with strong fire firstly and then decocted with slow fire for 30 minutes, the decoction is filtered, the two decoctions are combined and placed at 0 ℃ for standing for 24 hours, the mixture is filtered again to obtain an extracted liquid medicine, the extracted liquid medicine is subjected to reduced pressure concentration to remove a solvent, and the extracted liquid medicine is crushed into.

And the fourth step is to mix the medicine powder obtained in the first step to the third step together, add pharmaceutically acceptable auxiliary materials, mix uniformly, and directly press the mixture to obtain the tablet.

Advantageous technical effects

Detailed Description

The invention provides an attenuation and synergism traditional Chinese medicine tablet for treating wind-damp heat type gout, which comprises auxiliary materials and active ingredients, wherein the active ingredients comprise tripterygium wilfordii, phellodendron amurense, radix stephaniae tetrandrae, rhizoma anemarrhenae, rhizoma atractylodis, rhizoma smilacis glabrae, talcum, gentiana macrophylla, rhizoma dioscoreae hypoglaucae, radix cyathulae, polygonum cuspidatum and raw liquorice.

Wind-damp heat type gout belongs to the category of heat arthralgia and the calendar section in the traditional Chinese medicine, and is mostly caused by the fact that a large amount of alcohol drinking and overeating are fat, sweet and thick, dampness blocks middle-jiao, stagnation turns into heat, dampness and heat accumulates in joints, and stagnation blocks blood vessels. For the treatment, it is suitable to clear heat and remove toxicity, dispel dampness and relieve arthralgia, activate blood and resolve stasis. According to the traditional Chinese medicine, the tripterygium wilfordii is pungent and cool in property and toxic in property, has the effects of dispelling wind and removing dampness, and dredging collaterals and relieving pain, and is commonly used for treating diseases such as gout, rheumatoid arthritis and tumors. Modern pharmacological research considers that the treatment of gout by tripterygium glycosides is mainly realized by anti-inflammation and immunosuppression, and uric acid can be effectively reduced by compatibility of medicines, so that the medicine is used as a monarch medicine of the traditional Chinese medicine preparation; when tripterygium wilfordii is clinically used, the compatibility of attenuation and synergism of the tripterygium wilfordii is very careful, the traditional Chinese medicine preparation of the invention achieves better attenuation effect on the preparation process, and the effective components are retained to the maximum extent, the raw liquorice is used for harmonizing the effects of the traditional Chinese medicines, the attenuation and synergism are realized, and the attenuation mechanism of the tripterygium wilfordii as a monarch medicine can be considered that the liquorice activates Nrf₂ARE cell signaling pathway upregulation of Nrf₂The expression of the polypeptide can regulate and control the expression of downstream II-phase detoxification enzymes and drug transporters, play the advantage of multi-target action and promote the metabolism and excretion of toxicants in vivo, so that the liquorice is used as a messenger drug. Rhizoma Smilacis Glabrae has effects of clearing heat and promoting diuresis, and removing toxic substance, and can be used in combination with Glycyrrhrizae radix to reduce toxicity of radix Tripterygii Wilfordii; in addition, medicaments such as golden cypress, radix stephaniae tetrandrae, rhizoma anemarrhenae, large-leaved gentian, rhizoma dioscoreae hypoglaucae, polygonum cuspidatum, talc and the like are used, and the medicaments are matched with monarch medicaments for clearing heat, promoting diuresis, dredging collaterals and relieving pain, wherein the golden cypress and the rhizoma anemarrhenae have the effects of strengthening yin and clearing heat, the polygonum cuspidatum is stronger than the effect of clearing heat and purging fire, and the talc conducts heat downwards; radix cyathulae and rhizoma anemarrhenae are used as adjuvant drugs to supplement and nourish liver, lung and kidney.

The weight of each raw material medicine in the drug effect components is 30-40 g of tripterygium wilfordii, 20-30 g of phellodendron amurense, 10-20 g of radix stephaniae tetrandrae, 10-20 g of rhizoma anemarrhenae, 10-20 g of rhizoma atractylodis, 10-20 g of rhizoma smilacis glabrae, 10-20 g of talcum, 10-20 g of gentiana macrophylla, 10-20 g of rhizoma dioscoreae hypoglaucae, 10-20 g of radix cyathulae, 20-30 g of polygonum cuspidatum and 20-30 g of raw liquorice respectively, and the raw material medicines are extracted and prepared into tablets, wherein each tablet is 0.5 g.

The weight of each raw material medicine in the pharmacodynamic components is preferably 30-35 g of tripterygium wilfordii, 25-30 g of phellodendron amurense, 10-15 g of radix stephaniae tetrandrae, 10-15 g of rhizoma anemarrhenae, 10-15 g of rhizoma atractylodis, 10-15 g of rhizoma smilacis glabrae, 10-15 g of talcum, 10-15 g of gentiana macrophylla, 10-15 g of rhizoma dioscoreae septemlobae, 10-15 g of radix cyathulae, 25-30 g of polygonum cuspidatum and 25-30 g of raw liquorice.

The most preferable weight of each raw material medicine in the drug effect components is 35g of tripterygium wilfordii, 25g of phellodendron amurense, 10g of radix stephaniae tetrandrae, 15g of rhizoma anemarrhenae, 10g of rhizoma atractylodis, 10g of rhizoma smilacis glabrae, 10g of talcum, 15g of gentiana macrophylla, 10g of rhizoma dioscoreae septemlobae, 10g of radix cyathulae, 25g of polygonum cuspidatum and 25g of raw liquorice.

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

firstly, processing active ingredients of tripterygium wilfordii;

step two, processing the liquorice;

thirdly, processing the rest effective components;

fourthly, preparing the traditional Chinese medicine tablet.

The first step is further to uniformly wrap the tripterygium wilfordii with yellow mud, heat the tripterygium wilfordii with microwave, then knock off the yellow mud, brush off the loess on the surface, cut up, reflux-extract for 3 times with ethanol with the concentration of 70 percent by volume of 10 times of alcohol (volume percentage concentration), extract for 2 hours each time, combine and concentrate the extract, and decompress and dry the extract to obtain the tripterygium wilfordii extract dry powder, wherein the sum of the contents of other tripterygium wilfordii diterpene lactones except tripterygium wilfordii in the tripterygium wilfordii extract.

The yellow mud is prepared by uniformly mixing saline water with the mass concentration of 20% and sterile-treated dry loess according to the proportion of 1: 4, and then drying the mixture at the low temperature of less than 40 ℃ in a sterile environment to ensure that the water content of the loess is 10-15% to obtain the yellow mud.

The microwave is prepared for 10 minutes under the power of 60 percent (namely 480W) of a microwave oven (Galanz, 220V-50 Hz, 800W)) adopted by the microwave.

And (3) identification standard: the aqueous solution of radix Tripterygii Wilfordii extract dry powder contains triptolide (effective and toxic components composition, mainly comprising 8 components such as tripterine, triptolide, and tripterygium alkaloid), wherein the effective component is triptolide, other triptolide components are toxic components, and the content of triptolide and other triptolide components in the same batch of radix Tripterygii Wilfordii is different. The content of triptolide (effective component) is basically unchanged, and the sum of other triptolide (toxic component) is obviously reduced to be less than 10 percent, so that the preparation method for determining the toxicity reduction and synergism of the extract is effective. Otherwise the batch of drug is voided.

The second step is further specifically that liquorice is placed into an ultrafine grinder to be subjected to ultrafine grinding for 30 minutes to obtain ultrafine ground fine powder with the granularity of more than 400 meshes for later use, the liquorice is added into tablets, and the liquorice can activate Nrf₂ARE cell signaling pathway upregulation of Nrf₂The expression of the tripterygium wilfordii can be regulated, the expression of downstream II-phase detoxification enzymes and drug transporters can be regulated, the multi-target action advantage can be played, the metabolism and excretion of poisons in vivo can be promoted, and the effect of further attenuating tripterygium wilfordii can be achieved.

And the third step is further specifically that other raw material medicinal materials are respectively cleaned, crushed and mixed together, water with the mass 6-8 times that of the mixed medicinal materials in the step is added, the mixture is boiled with strong fire firstly, then decocted with slow fire for 1 hour, the decoction is filtered, the filter residue is added with water with the mass 4-6 times that of the mixed medicinal materials in the step again, the mixture is boiled with strong fire firstly, then decocted with slow fire for 30 minutes, the decoction is filtered, the two decoctions are combined, placed at 0 ℃ and kept still for 24 hours, filtered again to obtain extracted liquid medicine, the solvent is removed through concentration under reduced pressure, and the extracted liquid medicine is crushed into powder.

The pharmaceutically acceptable auxiliary materials are selected from one or more of diluents, binders, disintegrating agents and lubricants, wherein the diluents are selected from one or more of starch, dextrin, microcrystalline cellulose, β -cyclodextrin, mannitol, polyvinylpyrrolidone and sodium carboxymethylcellulose, the binders are selected from one or more of distilled water, ethanol and starch slurry, the disintegrating agents are selected from one or more of polyvinylpyrrolidone, polyethylene glycol and sodium lauryl sulfate, and the lubricants are selected from one or more of magnesium stearate and talcum powder.

The following embodiments are described in detail to solve the technical problems by applying technical means to the present invention, and the implementation process of achieving the technical effects can be fully understood and implemented.

Attenuation and synergism identification standard: the aqueous solution of radix Tripterygii Wilfordii extract dry powder contains triptolide (effective and toxic components composition, mainly comprising 8 components such as tripterine, triptolide, and tripterygium alkaloid), wherein the effective component is triptolide, other triptolide components are toxic components, and the content of triptolide and other triptolide components in the same batch of radix Tripterygii Wilfordii is different. The content of triptolide (effective component) is basically unchanged, and the sum of other triptolide (toxic component) is obviously reduced to be less than 10 percent, so that the preparation method for determining the toxicity reduction and synergism of the extract is effective. Otherwise the batch of drug is voided.

EXAMPLE 1 tablet 1

Taking saline water with the mass concentration of 20% and sterile-processed dry loess, uniformly mixing according to the mass ratio of 1: 4, and then drying at the low temperature of less than 40 ℃ in a sterile environment to ensure that the water content of the loess is 10-15% to obtain yellow mud.

Uniformly wrapping 35g of tripterygium wilfordii with yellow mud, roasting for 10 minutes by microwave heating, wherein the power of a microwave oven (Galanz, 220V-50 Hz, 800W)) is 60 percent, namely 480W, then knocking off the yellow mud, brushing off loess on the surface, chopping, extracting for 3 times by refluxing with ethanol with the volume concentration of 10 times being 70 percent (volume percentage concentration) for 2 hours each time, combining and concentrating the extracting solution, evaporating to dryness under reduced pressure to obtain tripterygium wilfordii extract dry powder, and detecting by high performance liquid chromatography, wherein the sum of the contents of diterpene lactones of the tripterygium wilfordii except tripterygium wilfordii in the tripterygium wilfordii extract dry powder is 8.6 percent.

Placing 25g of raw licorice into an ultramicro pulverizer to carry out ultramicro pulverization for 30 minutes to obtain ultramicro pulverized powder with the granularity of more than 400 meshes for later use.

Taking 25g of phellodendron, 10g of radix stephaniae tetrandrae, 15g of rhizoma anemarrhenae, 10g of rhizoma atractylodis, 10g of rhizoma smilacis glabrae, 10g of talcum, 15g of gentiana macrophylla, 10g of rhizoma dioscoreae hypoglaucae, 10g of radix cyathulae and 25g of polygonum cuspidatum, respectively cleaning, crushing, mixing, adding 1kg of water, boiling with strong fire, decocting with slow fire for 1 hour, filtering decoction, adding 850g of water into filter residue again, boiling with strong fire, decocting with slow fire for 30 minutes, filtering the decoction, combining the two decoctions, standing at 0 ℃ for 24 hours, filtering again to obtain an extracted liquid medicine, concentrating under reduced pressure to remove a solvent, and crushing into powder.

Mixing the above obtained medicinal powders, adding microcrystalline cellulose 10g and magnesium stearate 1g into 100g mixed powder, tabletting, mixing, directly tabletting, and coating film to obtain tablet 0.5g per tablet.

Pharmacological toxicity test

Firstly, experimental materials:

(one) experimental animals: ICR cleaning grade mice 40, 20 + -2 g, male and female. After purchase, adaptive breeding is carried out for 3 d.

(II) test drugs

1. The medicine of the invention is: the tablet of the invention is ground and shaken and dissolved in water to prepare the medicine for standby application, and each 1ml of liquid medicine contains 12.5g of crude drug.

(III) method of experiment

Taking 40 ICR mice, each half of the mice is divided into 2 groups at random, each group comprises 20 mice, the intragastric administration volume is 0.4ml/10g, 2 times/d, 6 hours are separated, the continuous administration is carried out for 7 days, and the autonomic activity, respiration, appetite, excrement and other indexes of all animals after the administration are observed; during the observation period, if the mouse died, the dissection was performed immediately.

(IV) test results

After administration, the behavior and activity of the mice are observed and recorded for 7 days continuously without obvious abnormal phenomena, each natural pore cavity has no abnormal secretion, the ingestion and drinking of water are normal, the urine and feces are normal, and the mice do not die.

(V) conclusion

The maximum tolerance amount is generally considered to be more than 100 times of the daily clinical dose of human, animals do not die, and the medicine is safe when no obvious toxic reaction occurs. The clinical planned dosage of the tablet is 3.75 g/day, the daily intake of a clinical person is 1500g/kg calculated according to 50g of crude drug/kg of the maximum tolerance of an experimental mouse, and the tolerance is 249.6 times of the clinical planned dosage of the tablet. Therefore, it is confirmed that the present drug is safe for clinical use.

Long term toxicity test of rats of the invention

Second, Experimental materials

(I) test drugs and drugs

After being ground, the tablet agent is shaken and dissolved in water to prepare the crude drug with the concentration of 12.5g/kg, 9.375g/kg and 6.25g/kg, the mixture is stored for standby at 4 ℃, the intragastric administration volume is 4ml/100g, 2 times/d and the interval is 6 hours.

(II) Experimental animals

SPF SD rats 260-300 g, 30 rats, each half of male and female. After purchase, adaptive breeding is carried out for 3 d.

(III) method of experiment

(1) Grouping and administration routes

30 SD rats, each half of male and female, were randomly divided into a control group, a high dose group, a medium dose group and a low dose group according to body weight, and the corresponding doses were 12.5g/kg/d, 9.375g/kg/d and 6.25 g/kg/d.

Each administration group is administrated with 20mL/kg by intragastric administration according to the dose, a control group is administrated with 20mL/kg of distilled water by intragastric administration according to the same method, the intragastric administration is adopted in the experiment, and the administration route is consistent with the clinical oral administration route.

(2) Method of administration

The tablet is administrated for 2 times/d in each dose group, is administrated by intragastric administration according to experimental requirements at an interval of 6 hours at 10 am, is administrated by intragastric administration of 20mL/kg in volume, and is administrated by intragastric administration of 20mL/kg in blank control group. Weighing the weight 1 time per week d, adjusting the dosage according to the weight, stopping the drug after continuously administering 42 times (1 course of clinical administration is 7-14 days), and recovering the observation period to 14 days after stopping the drug.

(IV) results of the experiment

After the rat is subjected to gastric lavage, the high dose of the invention is 12.5g/kg/d, (the planned dose for clinical adults is 62.4 times), the medium dose of the invention is 9.375g/kg/d, (the planned dose for clinical adults is 46.8 times), the low dose of the invention is 6.25g/kg/d, (the planned dose for clinical adults is 31.2 times), 2 times/day, after 42 days of continuous administration, the rat is compared with a control group to detect various indexes such as general state, body weight, food intake, water intake, organ coefficient, histopathology and the like, and no obvious toxicity sensitive index and toxicity target organ are found; after the medicine is stopped and the rats are recovered for 2 weeks, all detection indexes of the rats in the high, medium and low dose groups of the tablet are normal, and no delayed toxic reaction or accumulative toxic reaction is generated by the tablet. The test result shows that the tablet of the invention has no obvious toxic and side effect on rats after long-term application, and the intended dose and treatment course of clinical adults are in a safe range.

Clinical research

General data

156 cases were outpatient, 94 men and 62 women; randomly divided into a treatment group and a control group, wherein each group comprises 78 persons, 47 men and 31 women, and the average age of the treatment group is 48.5 +/-4.5 years; the mean age of the control group was 47.9. + -. 4.2 years, and there was no statistical difference in the disease status between the two groups.

Diagnostic criteria

Referring to the domestic common diagnosis standard, severe pain and tenderness at sudden metatarsophalangeal joints, tarsal joints, ankles, knee joints and the like, local red, swollen and hot, and blood uric acid is higher than 400 mu mol/L.

Method of treatment

Treatment groups: the traditional Chinese medicine preparation tablet prepared in the embodiment 1 of the invention is orally taken, one tablet is 0.5g, 3 tablets are taken every time, 2 times are taken every day, and 7 tablets are taken every day until the symptoms are relieved or adverse reactions occur. 30 days is a course of treatment, and the curative effect is counted after 1 course of treatment.

Control group: the colchicine is taken orally with 1mg of the first dose, 0.5mg after 1-2 hours and no more than 6mg after 24 hours until the symptoms are relieved or adverse reactions appear. 30 days is a course of treatment, and the curative effect is counted after 1 course of treatment.

4 standard of therapeutic effect

And (3) healing: the symptom disappears, the joint red swelling and hot pain subsides, and the blood uric acid returns to normal.

The effect is shown: the symptom disappears, the joint red swelling and hot pain subsides, and the blood uric acid returns to normal.

The method has the following advantages: the symptoms are obviously improved, the joint red swelling and hot pain basically subsides, and the blood uric acid is close to normal.

And (4) invalidation: the symptoms are not obviously improved, the joint red swelling and hot pain are not resolved, and the blood uric acid is not changed before and after the treatment, and the treatment attacks repeatedly.

5 therapeutic results

TABLE 1 comparison of the results of the two groups of treatments

Grouping	Recovery method	Show effect	Is effective	Invalidation	Total effective rate
						Treatment group	27	37	11	3	96.15％^＊
Control group	18	29	19	12	84.62％

Compared with the control group, the compound of the formula,^＊P＜0.05。

typical cases

Wangzhi, male, 48 years old, first diagnosis in 2016, 7 months and 5 days. Intermittent red swelling and hot pain of left ankle joint can be relieved by taking colchicine orally, and yesterday's left ankle joint is also severely painful, aversion to cold and fever, bitter taste in mouth and dark urine. The left ankle joint was examined for marked swelling, flushed skin, palpable fever and tenderness. The lateral aspect of the left ankle is marked by a red tongue with yellow and greasy coating and a slippery and rapid pulse. Blood uric acid 670. mu. mol/L. Gouty arthritis was diagnosed. The syndrome refers to downward flow of damp-heat and mutual accumulation of toxic and blood stasis. The Chinese medicinal preparation is administered by 3 tablets per time, 2 times per day and 7 tablets per day for 10 days, symptoms disappear after continuous administration, the medicine is added or subtracted for 1 month following the symptoms, the tongue is recurrent, the blood uric acid is 357 mu mol/L, no relapse is seen after 3 years of follow-up visit, and the blood uric acid is 344 mu mol/L is rechecked.

Experimental study

Laboratory animal

Male SD rats, body mass 200 + -20 g. Rats were equally divided into 4 groups according to the random block method design: model group, invention group, tripterygium non-attenuated group (non-attenuated group), colchicine group, 10 in each group, and local model making medication is started after 1 week of ordinary feed feeding.

Preparation of the model

The experimental urate ankle arthritis animal model is manufactured according to Coderre and Chen's method improvement. Weighing 10g of chloral hydrate, dissolving with distilled water, and diluting to 100mL to obtain 10% chloral hydrate solution for abdominal anesthesia of rats. 0.2g of sodium urate (manufactured by Sigma, batch No. 12OK5305, specification: 5g per bottle) is weighed, fully ground, added with 4mL of 0.9% sodium chloride injection to prepare 5% sodium urate suspension, aseptically operated, and injected with 0.2mL of 5% sodium urate solution into the tibialis and tarsal joint cavities of the right hind paw of each group of rats by a No. 4 injection needle, and each animal is injected for only 1 time. The needle probe and the joint capsule have a falling empty feeling, and the situation of the tibialis-tarsal joint cavity swelling is observed after the injection is finished.

Processing method

The medicine is started to be used after the model is successfully made for 6 hours, and the medicine is changed for treatment in 12 hours and 24 hours respectively.

Model group: only the model is made and the treatment is not carried out.

The invention group: the supernatant of the aqueous solution of the tablet of the present invention was administered at a crude drug concentration of 3g/ml by gavage for 2 times per day at a dose of 4ml/100g body weight.

Non-attenuated group: the medicine with the same concentration and dosage form as the invention group, which is prepared by the attenuation-free treatment of the tripterygium wilfordii, is administrated with supernatant of the attenuation-free Chinese medicine tablet water solution, the crude drug concentration is 3g/ml, and the medicine is administrated by gavage for 2 times/day according to 4ml/100g of body weight.

Colchicine group: preparing into 1mg/ml colchicine solution, and performing intragastric administration for 2 times/day according to 4ml/100g body weight.

Detecting the index

Toe volume, diameter and circumference values at 0.5mm below the left and right rear ankle joints of each group of rats were measured with a toe volume measuring instrument, a vernier caliper and a tape (the tape used was 6mm in width and 0.5mm in minimum scale), respectively.

The left and right ankles are measured before modeling as a measurement value of 0h, and the perimeter value and the diameter of the ankle and the volume of toes of a rat are measured 12 h, 24h and 48h after modeling respectively.

The swelling degree of the right hind foot (model side) arthritis at each time point was observed, and the swelling degree calculation formula was that the swelling ratio (%) - (Vt-Vn)/Vn × 100 was 100%, and Vn and Vt represent the volume values of toes before and after inflammation, respectively.

Statistical treatment

SPSS19.0 statistical software was applied. The metrology data is expressed in (x + -s). The significance test was performed by first using repeated measures of analysis of variance and by using unpaired t-test for comparison between groups. The mean value among multiple groups is compared by using single-factor variance analysis, and the front and back comparison in the groups adopts pairing t test. P < 0.05 is statistically significant.

Results

The swelling degree of toe is shown in tables 2 and 3.

TABLE 2 toe swelling Rate for each group

Rats in the tripterygium wilfordii non-attenuated group died 8 after administration, and the remaining 2 rats also had toxic symptoms, and the data were not objective, and therefore were not statistically analyzed.

In comparison with the set of models,^＊p is less than 0.05, compared with the invention group,^#P＜0.05

TABLE 3 increase ratio of joint diameter for each group

conclusion

Experimental research shows that the traditional Chinese medicine preparation has a good effect of treating gout, can well remove toxic components of tripterygium wilfordii through an attenuation method, and provides guarantee for clinical safe medication.

All of the above mentioned intellectual property rights are not intended to be restrictive to other forms of implementing the new and/or new products. Those skilled in the art will take advantage of this important information, and the foregoing will be modified to achieve similar performance. However, all modifications or alterations are based on the new products of the invention and belong to the reserved rights.

The foregoing is directed to preferred embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.

Claims

1. An attenuated synergistic traditional Chinese medicine tablet for treating gout with rheumatic fever is characterized in that: the traditional Chinese medicine composition is composed of active pharmaceutical ingredients and auxiliary materials, wherein the active pharmaceutical ingredients are composed of tripterygium wilfordii, phellodendron amurense, radix stephaniae tetrandrae, rhizoma anemarrhenae, rhizoma atractylodis, rhizoma smilacis glabrae, talcum, gentiana macrophylla, rhizoma dioscoreae hypoglaucae, radix cyathulae, polygonum cuspidatum and raw liquorice;

the weight of each raw material medicine in the pharmacodynamic components is 30-40 g of tripterygium wilfordii, 20-30 g of phellodendron amurense, 10-20 g of radix stephaniae tetrandrae, 10-20 g of rhizoma anemarrhenae, 10-20 g of rhizoma atractylodis, 10-20 g of rhizoma smilacis glabrae, 10-20 g of talcum, 10-20 g of gentiana macrophylla, 10-20 g of rhizoma dioscoreae hypoglaucae, 10-20 g of radix cyathulae, 20-30 g of polygonum cuspidatum and 20-30 g of raw liquorice respectively, and the raw material medicines are extracted and prepared into tablets, wherein each tablet is 0.5 g;

firstly, processing the active ingredients of tripterygium wilfordii, uniformly wrapping the tripterygium wilfordii with yellow mud, heating and roasting by microwave, then knocking off the yellow mud, brushing off loess on the surface, chopping, extracting for 3 times by refluxing with ethanol with the concentration of 70% by volume of 10 times of volume alcohol for 2 hours each time, combining and concentrating the extracting solution, and evaporating to dryness under reduced pressure to obtain tripterygium wilfordii extract dry powder, wherein the sum of the contents of other tripterygium diterpene lactones except tripterygium wilfordii in the tripterygium wilfordii extract dry powder is less than 10%;

step two, processing the liquorice;

thirdly, processing the rest effective components;

fourthly, preparing the traditional Chinese medicine tablet.

2. The toxicity-reducing and efficacy-enhancing traditional Chinese medicine tablet for treating gout with damp-heat type according to claim 1, wherein the toxicity-reducing and efficacy-enhancing traditional Chinese medicine tablet comprises: the weight of each raw material medicine in the drug effect components is 30-35 g of tripterygium wilfordii, 25-30 g of phellodendron amurense, 10-15 g of radix stephaniae tetrandrae, 10-15 g of rhizoma anemarrhenae, 10-15 g of rhizoma atractylodis, 10-15 g of rhizoma smilacis glabrae, 10-15 g of talcum, 10-15 g of gentiana macrophylla, 10-15 g of rhizoma dioscoreae hypoglaucae, 10-15 g of radix cyathulae, 25-30 g of polygonum cuspidatum and 25-30 g of raw liquorice.

3. The toxicity-reducing and efficacy-enhancing traditional Chinese medicine tablet for treating gout of rheumatic fever type according to claim 1 or 2, wherein: the weight of each raw material medicine in the pharmacodynamic components is respectively 35g of tripterygium wilfordii, 25g of phellodendron amurense, 10g of radix stephaniae tetrandrae, 15g of rhizoma anemarrhenae, 10g of rhizoma atractylodis, 10g of rhizoma smilacis glabrae, 10g of talcum, 15g of large-leaved gentian, 10g of rhizoma dioscoreae septemlobae, 10g of radix cyathulae, 25g of polygonum cuspidatum and 25g of raw.

4. The method for preparing a Chinese medicinal tablet according to claim 1 or 2, comprising:

firstly, processing active ingredients of tripterygium wilfordii;

step two, processing the liquorice;

thirdly, processing the rest effective components;

fourthly, preparing traditional Chinese medicine tablets;

the first step is further specifically that the tripterygium wilfordii is evenly wrapped by yellow mud, the yellow mud is roasted by microwave heating, then the yellow mud is knocked off, the loess on the surface is brushed off, the yellow mud is cut up, the yellow mud is extracted for 3 times by ethanol with the concentration of 10 times of volume alcohol being 70% volume percentage concentration, the extraction solution is merged and concentrated for 2 hours each time, the extraction solution is evaporated to dryness under reduced pressure, and the tripterygium wilfordii extract dry powder is obtained, wherein the sum of the contents of other tripterygium wilfordii diterpene lactones except triptolide in the.

5. The method for preparing a Chinese medicinal tablet according to claim 4, wherein: the yellow mud is prepared by taking saline water with the mass concentration of 20% and dry loess subjected to sterile treatment according to the weight ratio of 1: 4, mixing uniformly, and then drying at a low temperature of less than 40 ℃ in a sterile environment to ensure that the water content of the loess is 10-15 percent to obtain yellow mud.

6. The method for preparing a Chinese medicinal tablet according to claim 5, wherein: and the second step is further specifically that the liquorice is put into an ultrafine grinder to be subjected to ultrafine grinding for 30 minutes to obtain ultrafine ground fine powder with the granularity of more than 400 meshes for later use.

7. The method for preparing a Chinese medicinal tablet according to claim 6, wherein: and the third step is further specifically that other raw material medicinal materials are respectively cleaned, crushed and mixed together, water with the mass 6-8 times that of the mixed medicinal materials in the step is added, the mixture is boiled with strong fire firstly, then decocted with slow fire for 1 hour, the decoction is filtered, the filter residue is added with water with the mass 4-6 times that of the mixed medicinal materials in the step again, the mixture is boiled with strong fire firstly, then decocted with slow fire for 30 minutes, the decoction is filtered, the two decoctions are combined, placed at 0 ℃ and kept still for 24 hours, filtered again to obtain extracted liquid medicine, the solvent is removed through concentration under reduced pressure, and the extracted liquid medicine is crushed into powder.

8. The method for preparing a Chinese medicinal tablet according to claim 7, wherein: and the fourth step is to mix the medicine powder obtained in the first step to the third step together, add pharmaceutically acceptable auxiliary materials, mix uniformly, and directly press the mixture to obtain the tablet.