CN111569005A

CN111569005A - Traditional Chinese medicine composition for treating rheumatoid arthritis and preparation method thereof

Info

Publication number: CN111569005A
Application number: CN202010592367.2A
Authority: CN
Inventors: 李艳芳; 刘庆丰; 于祥玉; 于成帅
Original assignee: Lunan Pharmaceutical Group Corp
Current assignee: Lunan Pharmaceutical Group Corp
Priority date: 2020-06-24
Filing date: 2020-06-24
Publication date: 2020-08-25

Abstract

The invention discloses a traditional Chinese medicine composition for treating rheumatoid arthritis and a preparation method thereof, belonging to the field of traditional Chinese medicine preparations. The traditional Chinese medicine composition is prepared from honeysuckle, kadsura pepper stem, white paeony root, rehmannia root, spreading hedyotis herb, red-rooted salvia root, pyrola, Chinese angelica, szechuan lovage rhizome, Indian iphigenia bulb, liquoric root and scorpion, and has the effects of clearing away heat and toxic materials, promoting blood circulation to remove swelling, relieving arthralgia and relieving pain. Pharmacodynamic studies show that the traditional Chinese medicine composition can obviously inhibit primary lesions of rat adjuvant arthritis and reduce the incidence rate and the degree of secondary disease, and clinical curative effect observation results show that the traditional Chinese medicine composition has the same treatment effect with the existing Jinteng arthralgia-removing preparation, and can effectively avoid potential safety risks of caulis sinomenii and centipedes. The invention also provides a method for preparing the traditional Chinese medicine composition, and the traditional Chinese medicine composition can be prepared into granules, tablets, capsules or pellets.

Description

Traditional Chinese medicine composition for treating rheumatoid arthritis and preparation method thereof

Technical Field

The invention relates to a traditional Chinese medicine composition and a preparation method thereof, in particular to a traditional Chinese medicine composition for treating rheumatoid arthritis and a preparation method thereof, and belongs to the field of traditional Chinese medicines.

Background

Rheumatoid Arthritis (RA) is one of important diseases harmful to human health, has a high incidence rate in middle-aged and elderly people, seriously affects the life quality of patients, even causes disability in serious patients, and shortens life. The main symptoms of RA are characterized by red, swollen, hot and painful joints, local pounding heat of affected parts, untouchable pain, skin nodules, finger erosion, red eye photophobia, fever tiredness, aphthous stomatitis, tongue dryness, dry stool and violent pain such as insect and animal bites and the like. At present, no specific therapy is available for the patient, so the prevention and treatment of rheumatoid arthritis is one of the important subjects of research in the medical field. The etiology of RA is not yet determined by Western medicine, RA is considered as an autoimmune disease (also considered to be related to heredity and endocrine disorder) caused by sensing bacteria and viruses, the pathogenesis of RA is that after the bacteria or the viruses enter a body, an antigen-antibody immune complex is generated, so that erosion and destruction to joint synovium, blood vessels and cartilage are caused, and inflammatory reaction of red, swelling, heat and pain is formed; it is also accompanied by systemic vasculitis, and inflammatory damage to internal organs and organs such as heart, lung, and eye. The main medicinal means for treating the disease in western medicine are non-steroidal anti-inflammatory drugs, immunosuppressants, hormones and the like, but the side effects of long-term administration of the drugs are large and cannot be ignored.

According to the traditional Chinese medicine, RA belongs to the toxic heat arthralgia. For arthralgia due to toxic heat, the stagnation of toxic heat in the interior is caused by the failure of qi and blood to circulate and the generation of blood stasis and swelling. The pathogenesis of the disease is as follows: the preponderance of yang may cause the disease of the body, such as the recovery from exogenous pathogenic factors, the conflict between healthy qi and pathogenic factors, the obstruction of meridians, the stagnation of qi and blood, the stagnation of toxin and heat, the invasion of meridian into the joints, the burning of blood vessels, and even other diseases. Therefore, clinical treatment should be based on the principle of clearing away heat and toxic material, activating blood and relieving swelling, and relieving arthralgia and pain. At present, the traditional Chinese medicine has obvious and reliable curative effect on treating rheumatoid arthritis. Chinese patent CN1256134C discloses a Chinese medicinal composition prepared from honeysuckle, orientvine stem, oldenlandia diffusa, figwort root, rehmannia root, Indian iphigenia bulb, pyrola, white paeony root, Chinese angelica, liquorice and centipede as raw materials, which has the effects of clearing heat and removing toxicity, promoting blood circulation and relieving swelling, and relieving arthralgia and pain, and has a remarkable treatment effect on active-period rheumatoid arthritis. The product of the invention, named Jintenqingbi granules (national standard Z20123065), is a Chinese patent medicine product of Lunanqianpu pharmaceutical Co. Zhengxinchun and the like adopt random, contrast and multi-center clinical research methods, and prove that the curative effect of the jinteng qingbi granules on the rheumatoid arthritis in the active period is definite, the clinical symptoms, physical signs and various physicochemical indexes of patients with the rheumatoid arthritis in the active period can be obviously improved after 8 weeks of treatment, the total effective rate reaches 95.2%, and no obvious toxic and side effect is caused (Zhengxinchun, et al, Hubei Chinese medicine J., 35 rd volume 3 rd in 2013).

The Sinomenium acutum which is a monarch drug in the formula of the Sinomenium acutum granules is dry vine of Sinomenium acutum (Thunb.) Rehd. et wils. and Sinomenium acutum (Thnnh.) Rehd. et wils. var. cinereum Rehd. et wils. of Menispermum, Sinomenium acutum, wherein Sinomenium acutum is recorded in the section of 2015 of Chinese pharmacopoeia. Caulis sinomenii has the effects of expelling wind-damp, dredging the channels and collaterals and promoting urination, and is a key medicine for treating rheumatic arthritis. As a common traditional Chinese medicine, the use of the caulis sinomenii and the finished preparation thereof in the treatment and prevention of diseases is more and more extensive, and people have more and more deep knowledge on the safety of the caulis sinomenii. However, in recent years, reports of adverse reactions of caulis sinomenii and preparations thereof, particularly adverse effects on human immunosuppression, are increasing at home and abroad, so that potential safety risks of the traditional Chinese medicine decoction pieces and the traditional Chinese medicines are concerned by various social circles.

The centipede in the formula of the Jinteng qingbi particles is a dried body of Scolopendra subspinipes mutilans L.Koch which is a centipede. The centipede has the effects of calming wind, relieving convulsion, dredging collaterals, relieving pain, counteracting toxic substances and dissipating stagnation, and is clinically used for treating liver wind stirring and rheumatism arthralgia. Because the medicinal materials are used as raw powder, the medicinal materials have stronger fishy smell and poor compliance of patients; centipede is a toxic animal, and the toxicity and the drug effect of different species are different; the centipede medicinal materials are expensive and are precious and fine Chinese medicinal materials, and meanwhile, because different centipedes have larger similarity in form, the centipede medicinal materials have the phenomena of artificial or unintentional confusion and misuse for a long time, and potential harm is caused to human health.

Disclosure of Invention

Aiming at the problems faced by 2 medicaments of caulis sinomenii and centipede in the formula of the caulis sinomenii cleaning and paralysis particle, the invention provides a Chinese medicinal composition for treating rheumatoid arthritis and a preparation method thereof on the basis of a formula and a preparation method (Chinese patent CN1256134C) of the caulis sinomenii cleaning and paralysis particle, aiming at avoiding possible immunosuppression risk of the caulis sinomenii after long-term administration based on scientific and judicious attitude, and simultaneously avoiding the defects of poor compliance of patients and toxicity difference of different varieties when a centipede preparation is used.

One of the technical purposes of the invention is to provide a traditional Chinese medicine composition for treating rheumatoid arthritis, which is prepared from honeysuckle, kadsura pepper stem, white paeony root, rehmannia root, spreading hedyotis herb, salvia miltiorrhiza, pyrola, Chinese angelica, szechuan lovage rhizome, Indian iphigenia bulb, liquorice and scorpion, and has the effects of clearing away heat and toxic materials, promoting blood circulation and relieving swelling, and relieving arthralgia and pain. The 2 medicaments of the caulis sinomenii and the centipede in the original formula are effectively replaced in a targeted way by the caulis piperis futokadsurae and the scorpion, the radix scrophulariae in the formula is replaced by the salvia miltiorrhiza, and the ligusticum wallichii is added to activate blood and promote qi circulation, dispel wind and relieve pain in combination with the characteristic of the rheumatoid arthritis toxic heat arthralgia, so that the functional indication and the definite clinical curative effect of the caulis sinomenii arthralgia removing granules are basically kept, the effects of activating blood and removing stasis are enhanced, the unpleasant odor of the medicaments is improved, the compliance of patients is improved, and the possible toxicity risk can be avoided.

The technical purpose of the invention is realized by the following technical scheme:

a traditional Chinese medicine composition for treating rheumatoid arthritis is prepared from the following traditional Chinese medicine components:

the above-mentioned Chinese medicinal composition is preferably:

the above-mentioned Chinese medicinal composition is preferably:

the traditional Chinese medicine considers that the damp-heat arthralgia is caused by two ends, namely that the yang-preponderance constitution is caused by the exogenous pathogenic factor and that the yang-preponderance constitution is caused by the toxic heat. The pathogenesis of the disease is as follows: when the patient is infected with toxic heat, the exogenous pathogenic factors invade the interior and flow into the meridians and collaterals to be confined in the joints; the latter struggles between the body resistance and pathogenic factors, burns the blood vessels, and causes the fire to flow into the joints. Tang Dynassia Simiao with Rhinocerotis decoction for clearing away heat and toxic materials can be used for treating the syndrome of heat toxin flowing into limbs and swelling and pain in the calendar joint; qing dynasty Wu Ju general Xuanbi Tang, modified mu Fang Tang for treating damp-heat arthralgia, and said: the reason for arthralgia is that cold syndrome is usually more firm, while arthralgia is accompanied by heat syndrome, many cases are also complicated. It is clear that not only arthralgia due to wind-cold-dampness but also arthralgia due to long-term retention of qi and blood due to toxic heat. Therefore, the invention takes the treatment principle of clearing away heat and toxic material, promoting blood circulation to reduce swelling, dredging paralysis and relieving pain as the treatment principle.

In the prescription, honeysuckle flower, sweet and cold in nature and taste, has the functions of clearing away heat and toxic materials, dispelling wind and dredging collaterals. Not only treat red, swelling, heat and pain caused by internal pathogenic factors, but also disperse the toxic heat arthralgia caused by external toxic heat; kadsura pepper stem, pungent, bitter and slightly warm in nature and flavor, has the functions of dispelling wind-damp, dredging meridians and collaterals and relieving arthralgia, and is mainly used for treating wind-cold-damp arthralgia, limb joint pain, spasm of tendons and vessels and difficulty in flexion and extension. Furthermore, the modern medicine considers that RA is an immunological disease, and honeysuckle which is a good medicine for improving immunity and kadsura pepper stem which is an immunoregulation medicine are used for treating tangent pathogenesis, so the two medicines are selected as the monarch medicines.

Rehmannia root, radix rehmanniae, sweet and bitter in nature and cool in nature, has the functions of clearing heat, cooling blood and promoting blood circulation, and is mainly used for treating fever due to yin deficiency, diabetes, paralysis of qi, exhaustion, blood arthralgia, constipation and other symptoms; oldenlandia diffusa, bitter, sweet and cold in nature, has the functions of clearing heat and removing toxicity, and removing blood stasis and relieving swelling, and is mainly used for treating toxic heat swelling and pain; dan Shen is bitter and slightly cold in taste, has the actions of activating blood and resolving stasis, unblocking meridians and collaterals, clearing heart and relieving restlessness, cooling blood and resolving carbuncle, and is indicated for chest stuffiness and pain, heat stuffiness and pain. The three medicines not only help the honeysuckle to clear heat and detoxify the deficiency of nutrient blood, heart, liver and kidney channels, but also have the functions of cooling blood, nourishing yin, dissipating blood stasis and relieving swelling; the medicine has bitter and pungent properties, is sweet and cold, is clear but not dry, and is moist but not greasy, so that the medicine can better exert the medicine effect without disadvantages. White peony root, sweet and sour in nature, has the functions of nourishing blood and liver, relieving spasm and pain and smoothing blood vessels, is mainly used for treating rheumatoid joint contracture pain, blood impediment, red swelling, yin deficiency and fever, and has the effect of assisting caulis piperis futokadsurae in relieving pain; the edible tulip is sweet in nature and taste, slightly pungent and cold in nature, has the functions of clearing heat and removing toxicity, and relieving swelling and dissipating stagnation, and is mainly used for treating toxic heat red swelling and phlegm fire running injection so as to help the monarch drugs to relieve toxicity and relieve swelling; herba Pyrolae is sweet, bitter and warm in nature and has the effects of tonifying deficiency, benefiting qi, dispelling wind, removing dampness, promoting blood circulation and regulating menstruation, and is mainly used for treating rheumatic arthralgia, weakness of waist and knees and muscle and bone pain so as to enhance the effect of monarch drug in treating sinew and bone pain. The three medicines strengthen the effect of the kadsura pepper stem in relieving swelling, arthralgia and pain. Therefore, the six medicines are used as ministerial medicines.

Chinese angelica, sweet and pungent in nature and warm in nature, has the functions of tonifying blood and regulating blood, regulating menstruation and relieving pain, and moistening dryness and lubricating intestines, and is mainly used for treating symptoms such as rheumatic arthralgia, swelling of whole body and the like; chuan Xiong, pungent in flavor and warm in nature, has the functions of activating blood and qi, dispelling wind and alleviating pain, and is mainly used for treating rheumatic arthralgia and chest stuffiness and pains; the two herbs are used together with Dihuang and Bai Shao to nourish blood and harmonize blood for treating blood injury due to toxic heat, activate blood and relieve arthralgia so as to enhance the overall pain-relieving effect, so they are assistant drugs. Licorice root, radix Glycyrrhizae is bitter and neutral in nature and has the actions of regulating the middle warmer, relieving urgency, clearing heat and removing toxicity, and harmonizing the actions of the other drugs. It is used together with Shao powder to strengthen the pain-relieving power, and also used as adjuvant drug.

Scorpion, pungent and warm in property and flavor, has the actions of extinguishing wind, relieving spasm, unblocking collaterals, alleviating pain, counteracting toxic pathogen and dissipating nodulation, and is used for treating joint pain and swelling, and is used as a guiding drug to guide various herbs into the channels and collaterals to treat obstinate arthralgia. The medicines are combined to play the roles of clearing away heat and toxic materials, promoting blood circulation to reduce swelling, dredging arthralgia and relieving pain.

The invention also aims to provide an oral solid pharmaceutical preparation containing the traditional Chinese medicine composition and a preparation method thereof, wherein the oral solid pharmaceutical preparation is one of granules, tablets, capsules or pellets.

The preparation method of the oral solid pharmaceutical preparation comprises the following steps:

A. pulverizing Scorpio and 1/2 formula amount of radix Angelicae sinensis into fine powder, respectively, sieving with 100 mesh sieve, and sterilizing to obtain Scorpio fine powder and radix Angelicae sinensis fine powder;

B. adding water into flos Lonicerae, heating to boil, heat-preserving at 70-90 deg.C, hot-soaking, extracting for 1-3 times, each time for 1-2 hr, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.15-1.20 at 50-60 deg.C, adding ethanol to make ethanol content reach 60-80%, standing for 24 hr, collecting supernatant, recovering ethanol, concentrating to obtain soft extract with relative density of 1.25-1.30 at 50-60 deg.C, vacuum drying, pulverizing, and sieving with 100 mesh sieve to obtain flos Lonicerae extract fine powder;

C. extracting caulis Piperis Futokadsurae and herba Hedyotidis Diffusae with 70% ethanol under reflux for 2 times, each for 2 hr, filtering, mixing filtrates, and recovering ethanol to obtain medicinal liquid I;

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.15-1.20 at 50-60 deg.C, cooling, adding 95% ethanol to ethanol content of 50-70%, standing for 24 hr, collecting supernatant, and recovering ethanol to obtain medicinal liquid II;

E. mixing the liquid medicine I and the liquid medicine II, concentrating to obtain thick paste with the relative density of 1.25-1.30 at 50-60 ℃, vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain composite extract fine powder for later use;

F. mixing the flos Lonicerae extract fine powder obtained in step B and the compound extract fine powder obtained in step E, adding the Scorpio fine powder and radix Angelicae sinensis fine powder obtained in step A, mixing, adding conventional adjuvants, and making into granule, tablet, capsule or pellet.

Preferably, step B comprises the steps of:

adding water into honeysuckle, heating to boil, keeping the temperature at 90 ℃, carrying out hot dipping for 2 times, extracting for 1.5 hours each time, filtering, combining the filtrates, concentrating to obtain clear paste with the relative density of 1.18 at the relative density of 50-60 ℃, adding ethanol to ensure that the ethanol content reaches 70%, standing for 24 hours, taking the supernatant, recovering the ethanol, concentrating to obtain thick paste with the relative density of 1.27 at the relative density of 50-60 ℃, carrying out vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain honeysuckle extract fine powder for later use.

Preferably, step D comprises the steps of:

decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.18 at 50-60 deg.C, adding 95% ethanol to make ethanol content reach 60%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

The invention also discloses application of the traditional Chinese medicine composition in preparing a medicine for treating rheumatoid arthritis.

In order to verify the efficacy of the traditional Chinese medicine composition for treating rheumatoid arthritis, the inventor develops pharmacodynamic test research and medicine clinical research. It should be noted that the drug selected in the pharmacodynamic test and clinical study of the drug of the present invention is a drug obtained by the representative formulation and the preparation method thereof, and the tests and results related to the other formulations and the drugs obtained by the preparation method of the present invention are not exhaustive due to space limitations.

Experimental example 1 Effect on Primary lesions of adjuvant arthritis in rats

1 Material

1.1 Experimental animals

60 Wistar rats, half male and half female, weight 180-220 g, provided by the Experimental animal center of Chinese medical academy of sciences, and the qualification number: 92090R 18. Animals are raised in cages in a special laboratory, the animals are adaptively raised for one week before the experiment, the animals are separated from the males and the females, the animals are naturally illuminated, the animals freely eat drinking water, the room temperature is controlled to be 20-22 ℃, and the relative humidity is controlled to be 45-65%.

1.2 instruments, reagents and drugs

PV-200 toe volume measurement (Chengtai Union technologies, Inc.); an XS204 electronic analytical balance (Mettler-Toledo, Switzerland); medifuge Small bench centrifuge (Thermo Fisher, USA); DW-86L626 type ultra-low temperature storage box (Qingdao Haier Special appliances Co., Ltd.).

An inflammation-causing agent: the homemade Freund's complete adjuvant contains 8mg of tubercle bacillus and standard human type virulent tubercle bacillus (H37RV) per ml of emulsion adjuvant, and is provided by bacterin chambers of biological product assay of Ministry of health. The drug tested was a granulate prepared according to the formulation and process described in example 5; the positive control drug is Jintengqingbi granules (specification: 10 g/bag, batch No. 06718013, manufactured by Lunan Kangpu pharmaceutical Co., Ltd.).

2 method

2.1 grouping and administration

Taking 60 healthy rats, dividing the rats into 6 groups by adopting a random number table remainder method, wherein each group comprises 10 rats, and each rat is divided into a normal control group, a model control group, a positive control group, a test high dose group, a test medium dose group and a test low dose group by half of a male rat and a female rat. Five groups of animals except the normal control group were subjected to inflammation by injecting 0.05 ml/rat foot with 8mg/ml of Freund's complete adjuvant of tubercle bacillus necroseus subcutaneously. After the inflammation treatment, the test high, medium and low dose groups are sequentially administrated with 15g/kg/d, 7.5g/kg/d and 3.75g/kg/d of test drugs for intragastric administration; 7.5g/kg/d of the Jinteng qingbi particles are given to the positive control group for intragastric administration; the normal control group and the model control group were administered with the same amount of 0.9% NaCl solution for intragastric administration for 3 days.

2.2 indexes and methods for detection 2, 4, 6, 24 and 48 hours after inflammation, the volumes of the foot sole and the ankle joint of the foot with inflammation are measured by a capillary amplification measuring method, and the swelling rate is calculated.

Swelling rate (%) - (volume of postinflammatory metatarsal-volume of proinflammatory metatarsal)/volume of proinflammatory metatarsal × 100%

2.3 statistical methods SPSS19.0 statistical software was used for analytical processing. Experimental data are expressed as mean ± sd

"Format means comparison of differences between groups using one-way analysis of variance, with P <0.05 indicating that the differences are statistically significant.

3 results of the experiment

The swelling of the foot and ankle joints after the injection of the antigen for 2 hours in the model control group is increased with the increase of time, and the difference is statistically significant compared with the normal control group (P < 0.05). Compared with a model control group, the experimental high, medium and low dose groups can obviously inhibit primary lesion of the rat adjuvant arthritis at each time point, the difference has statistical significance (P <0.05), the positive control group also has better inhibition effect 2, 4, 6 and 24 hours after inflammation causing, and the difference has statistical significance (P < 0.05). The results are shown in Table 1.

TABLE 1 Effect of Primary lesions in adjuvant arthritis in rats Experimental results (

％，n＝10)

Note: comparison with normal control group: p <0.05 for "^△"means;

comparison with model control group: p <0.05 is indicated by ". times..

Experimental example 2 Experimental study on prevention and treatment effects of secondary lesions of adjuvant arthritis in rats

1 Material

1.1 Experimental animals

Wistar rat, male, weight 150-180 g, provided by the Experimental animal center of Chinese medical academy of sciences, certificate number: i. 01-3008, No. II animal. Animals were housed in special laboratories (class II quality permit number: 01-4010). The animal is adaptively raised in a clean animal laboratory for 1 week before experiment, the room temperature is 20-25 ℃, the relative humidity is 40% -60%, and the animal is naturally illuminated, and freely ingests and drinks water.

1.2 instruments, reagents and drugs

An inflammation-causing agent: freund's complete adjuvant containing inactivated human tubercle bacillus, inactivated human tubercle bacillus H37RV (standard human type virulent tubercle bacillus), 100 mg/count, provided by the biological product assay of Ministry of health, lot number 990011. The emulsion adjuvant contains 10mg of tubercle bacillus per ml. The drug used in this test was the same as in example 1.

2 method of experiment

2.1 grouping and dosage

Experimental animals were divided into 5 groups, (1) model control group: 0.9% NaCl solution; (2) positive control group (jinteng qingbi granule group): the administration dose is 7.5 g/kg; (3) trial high dose group: the administration dose is 15 g/kg; (4) dose groups in the experiment: the administration dose is 7.5 g/kg; (5) the low dose group was tested: the dose administered was 3.75 g/kg.

2.2 Molding and administration

After the experimental animals were acclimatized in a dedicated laboratory for 1 week, 106 well-growing, healthy rats were selected, 12 of which were used as model control groups, 45 for observation of preventive effects and 49 for observation of therapeutic effects. All animals were treated with Freund's complete adjuvant subcutaneously in the right hind paw of each rat at a dose of 0.1 ml/mouse.

45 rats for observation of preventive effect are randomly divided into 4 groups on the 7 th day after inflammation causing, namely a positive control group, test high, middle and low dose groups, and are subjected to intragastric administration for 1 time/day according to the dose together with a model control group for 10 days (to the 17 th day after inflammation causing), and the preventive effect of the medicine on adjuvant arthritis secondary lesion is observed on the 18 th day.

After the secondary lesions of 6 sites of the right hind foot, forelimb, ears, tail and the like of each rat were recorded on the 18 th day after inflammation, the 49 rats for observation of treatment effect were divided into 4 groups according to the body weight and the lesion degree, namely a positive control group, a test high, middle and low dose group. Treatment was given for 10 days as above dose and method, along with model control group. So that the incidence and severity of systemic arthropathy were recorded 29 days after inflammation.

2.3 index determination of pathological change degree of each part of each rat is scored according to the following standard, and the pathological change degree of the joints of the four limbs is represented by a six-grade scoring method: level 0: no red and swollen (-); level 1: little swelling of the little toe joint (±); and 2, stage: significant swelling of the little toe (+); and 3, level: swelling of the toe and plantar joints (++); 4, level: swelling of the foot below the ankle (+ ++); and 5, stage: swelling of all paws, including the ankle joint (++++). The degree of the tail joint lesion is represented by a five-grade scale method: level 0: no red swelling and nodules; level 1: the individual joints form nodules; and 2, stage: swelling of multiple joints; and 3, level: 1/2 above the joints form nodules with red and swollen; 4, level: all joints form nodules with red swelling. Ear lesions were represented on a four-point scale: level 0: no red swelling; level 1: mild red swelling; and 2, stage: moderate red and swollen; and 3, level: severe red and swollen.

2.4 statistical processing SPSS19.0 statistical software was used for analysis, and experimental data were expressed as mean. + -. standard deviation

"is expressed in terms of form. The comparison among groups was performed by one-way anova, with P <0.05 indicating that the difference was statistically significant.

3 results of the experiment

The above pathological changes are indicated by incidence and severity of pathological changes²The significance of the difference between the model control group and the administered group was compared by assay and Ridit analysis.

Incidence rate (%) is (total number of sites-number of sites where lesions occur)/total number of sites × 100%

Total number of observation sites per mouse (6) × number of animals per group

After the rats are subjected to prophylactic gavage for 10 days by using test samples with different doses, compared with a model control group, the high-dose, medium-dose and low-dose groups and the positive control group can obviously reduce the incidence rate of secondary lesions (P is less than 0.05). The results are shown in Table 2.

TABLE 2 comparison of incidence of Secondary lesions in prevention groups

After the rats are subjected to prophylactic gavage for 10 days by using test samples with different doses, compared with a model control group, the morbidity degree of a test high-dose group, a test medium-dose group and a test positive control group is remarkably reduced (P is less than 0.05); the low dose group tested had lighter lesions than the model control group, but did not reach statistical significance. The results show that the medicine can reduce the degree of secondary pathological changes. The results are shown in Table 3.

TABLE 3 comparison of severity of Secondary lesions in prevention group

After the rats are subjected to therapeutic gavage and given with different doses of test samples for 10 days, compared with a model control group, the incidence rate of secondary diseases of a high-dose group, a medium-dose group and a positive control group is obviously lower than that of the control group, the difference is significant (P is less than 0.05), and the effect of a low-dose group is not obvious. The results are shown in Table 4.

TABLE 4 comparison of incidence of Secondary lesions in treatment groups

After the rats are subjected to therapeutic gavage and given different doses of test samples for 10 days, compared with a model control group, the incidence degree of the test high and medium dose groups and the positive control group is remarkably reduced (P is less than 0.05); the low dose group tested had lighter lesions than the model control group, but did not reach statistical significance. The results show that the medicine can reduce the degree of secondary pathological changes. The results are shown in Table 5.

TABLE 5 comparison of severity of Secondary lesions in the treatment groups

Detailed Description

The present invention is further illustrated by the following specific examples, which are not intended to limit the invention in any way, as will be appreciated by those skilled in the art.

EXAMPLE 1 preparation of tablets

B. adding water into flos Lonicerae, heating to boil, heat-preserving at 80 deg.C, extracting for 3 times, each for 1 hr, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.16 at 50-60 deg.C, adding ethanol to make ethanol content reach 80%, standing for 24 hr, collecting supernatant, recovering ethanol, concentrating to obtain soft extract with relative density of 1.28 at 50-60 deg.C, vacuum drying, pulverizing, and sieving with 100 mesh sieve to obtain flos Lonicerae extract fine powder for use.

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.17 at 50-60 deg.C, adding 95% ethanol to make ethanol content reach 70%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

E. Mixing the liquid medicine I and the liquid medicine II, concentrating to obtain thick paste with the relative density of 1.28 at 50-60 ℃, vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain composite extract fine powder for later use;

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding microcrystalline cellulose and sodium carboxymethyl starch (the weight ratio is 3: 1) in a formula amount, uniformly mixing, preparing coarse granules, drying, crushing, sieving, preparing granules, drying at a low temperature, finishing granules, adding 0.3% of magnesium stearate and 0.1% of talcum powder, uniformly mixing, pressing into 10000 tablets, and coating a film coat to obtain the traditional Chinese medicine composition.

EXAMPLE 2 preparation of granules

B. adding water into flos Lonicerae, heating to boil, heat-preserving at 90 deg.C, hot-soaking for 1 time, extracting for 2 hr each time, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.19 at 50-60 deg.C, adding ethanol to make ethanol content reach 70%, standing for 24 hr, collecting supernatant, recovering ethanol, concentrating to obtain soft extract with relative density of 1.26 at 50-60 deg.C, vacuum drying, pulverizing, and sieving with 100 mesh sieve to obtain flos Lonicerae extract fine powder for use.

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.16 at 50-60 deg.C, adding 95% ethanol to make ethanol content reach 60%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

E. Mixing the liquid medicine I and the liquid medicine II, concentrating to obtain thick paste with the relative density of 1.30 at 50-60 ℃, vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain composite extract fine powder for later use;

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding the sucrose powder, the hydroxypropyl starch and the mannitol (in a weight ratio of 5: 2: 2) according to the formula, uniformly mixing, granulating, drying, and finishing to obtain 10 kg.

EXAMPLE 3 preparation of capsules

B. adding water into flos Lonicerae, heating to boil, heat-preserving at 70 deg.C, hot-soaking for 2 times, extracting for 1.5 hr each time, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.17 at 50-60 deg.C, adding ethanol to make ethanol content reach 60%, standing for 24 hr, collecting supernatant, recovering ethanol, concentrating to obtain soft extract with relative density of 1.30 at 50-60 deg.C, vacuum drying, pulverizing, and sieving with 100 mesh sieve to obtain flos Lonicerae extract fine powder for use.

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.19 at 50 deg.C-60 deg.C, adding 95% ethanol to make ethanol content reach 50%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

E. Mixing the liquid medicine I and the liquid medicine II, concentrating to obtain thick paste with the relative density of 1.25 at 50-60 ℃, vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain composite extract fine powder for later use;

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding the starch and the microcrystalline cellulose (the weight ratio is 5: 1) according to the formula amount, uniformly mixing, granulating, drying, grading, filling, polishing in a polishing machine, and removing damaged capsules to obtain the traditional Chinese medicine composition.

EXAMPLE 4 preparation of tablets

B. adding water into flos Lonicerae, heating to boil, heat-preserving at 80 deg.C, extracting for 2 times, each for 2 hr, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.20 at 50-60 deg.C, adding ethanol to make ethanol content reach 80%, standing for 24 hr, collecting supernatant, recovering ethanol, concentrating to obtain soft extract with relative density of 1.25 at 50-60 deg.C, vacuum drying, pulverizing, and sieving with 100 mesh sieve to obtain flos Lonicerae extract fine powder for use.

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.20 at 50-60 deg.C, adding 95% ethanol to make ethanol content reach 70%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

E. Mixing the liquid medicine I and the liquid medicine II, concentrating to obtain thick paste with the relative density of 1.27 at 50-60 ℃, vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain composite extract fine powder for later use;

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding starch, dextrin and cane sugar (the weight ratio is 4: 0.5: 1) according to the formula amount, uniformly mixing, preparing coarse granules, drying, crushing, sieving, preparing granules, drying at low temperature, grading, adding 0.4% of magnesium stearate, uniformly mixing, pressing into 10000 tablets, and coating a film coat to obtain the traditional Chinese medicine composition.

EXAMPLE 5 preparation of granules

B. adding water into honeysuckle, heating to boil, keeping the temperature at 90 ℃, carrying out hot dipping for 2 times, extracting for 1.5 hours each time, filtering, combining the filtrates, concentrating to obtain clear paste with the relative density of 1.18 at the relative density of 50-60 ℃, adding ethanol to ensure that the ethanol content reaches 70%, standing for 24 hours, taking the supernatant, recovering the ethanol, concentrating to obtain thick paste with the relative density of 1.27 at the relative density of 50-60 ℃, carrying out vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain honeysuckle extract fine powder for later use.

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.18 at 50-60 deg.C, adding 95% ethanol to make ethanol content reach 60%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

E. Mixing the liquid medicine I and the liquid medicine II, concentrating to obtain thick paste with the relative density of 1.26 at 50-60 ℃, vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain composite extract fine powder for later use;

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding the sucrose powder and the dextrin (weight ratio is 3: 1) according to the formula amount, uniformly mixing, granulating, drying, and finishing to obtain 10 kg.

EXAMPLE 6 preparation of capsules

B. adding water into flos Lonicerae, heating to boil, heat-preserving at 70 deg.C, hot-soaking for 3 times, extracting for 2 hr each time, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.17 at 50-60 deg.C, adding ethanol to make ethanol content reach 60%, standing for 24 hr, collecting supernatant, recovering ethanol, concentrating to obtain soft extract with relative density of 1.29 at 50-60 deg.C, vacuum drying, pulverizing, and sieving with 100 mesh sieve to obtain flos Lonicerae extract fine powder for use.

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.15 at 50 deg.C-60 deg.C, adding 95% ethanol to make ethanol content reach 50%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding the starch and the micro silica gel (the weight ratio is 3: 1) according to the formula amount, uniformly mixing, granulating, drying, grading, filling, polishing in a polishing machine, and removing damaged capsules to obtain the traditional Chinese medicine composition.

EXAMPLE 7 preparation of granules

B. adding water into flos Lonicerae, heating to boil, heat-preserving at 80 deg.C, extracting for 2 times, each for 1 hr, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.15 at 50-60 deg.C, adding ethanol to make ethanol content reach 70%, standing for 24 hr, collecting supernatant, recovering ethanol, concentrating to obtain soft extract with relative density of 1.28 at 50-60 deg.C, vacuum drying, pulverizing, and sieving with 100 mesh sieve to obtain flos Lonicerae extract fine powder for use.

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.18 at 50-60 deg.C, adding 95% ethanol to make ethanol content reach 70%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

E. Mixing the liquid medicine I and the liquid medicine II, concentrating to obtain thick paste with the relative density of 1.29 at 50-60 ℃, vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain fine powder of the compound extract for later use;

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding the sucrose powder, the hydroxypropyl starch and the mannitol (in a weight ratio of 4: 2: 1) according to the formula, uniformly mixing, granulating, drying, and finishing to obtain 10 kg.

EXAMPLE 8 preparation of pellets

1) Extraction process

B. adding water into honeysuckle, heating to boil, keeping the temperature at 90 ℃, carrying out hot dipping for 1 time, extracting for 1.5 hours each time, filtering, combining the filtrates, concentrating to obtain clear paste with the relative density of 1.16 at the relative density of 50-60 ℃, adding ethanol to ensure that the ethanol content reaches 80%, standing for 24 hours, taking the supernatant, recovering the ethanol, concentrating to obtain thick paste with the relative density of 1.29 at the relative density of 50-60 ℃, carrying out vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain honeysuckle extract fine powder for later use.

D. decocting radix Paeoniae alba, rehmanniae radix, Saviae Miltiorrhizae radix, herba Pyrolae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Pseudobulbus Cremastrae seu pleiones, Glycyrrhrizae radix and 1/2 formula amount radix Angelicae sinensis with water for 2 times, 2 hr for the first time and 1 hr for the second time, filtering, mixing filtrates, concentrating to fluid extract with relative density of 1.17 at 50-60 deg.C, adding 95% ethanol to make ethanol content reach 60%, standing for 24 hr, collecting supernatant, recovering ethanol to obtain liquid medicine II.

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, and uniformly mixing to obtain 3.24kg of extract fine powder.

2) Preparation process

A. Mailuoshutong extract fine powder: 3.24kg

B. Microcrystalline cellulose: 3.64kg

Dextrin: 1.82kg

C. Sodium carboxymethyl starch: 0.65kg

Silica gel micropowder: 0.65kg

Weighing the fine powder of the extract of the venation dredging in the step 1), microcrystalline cellulose, dextrin, sodium carboxymethyl starch and superfine silica powder in the formula amount respectively, fully and uniformly mixing, adding 52% (by weight) of ethanol solution with the concentration of 40% in the formula amount as a wetting agent, continuously kneading to prepare soft materials, and extruding the soft materials into strips through a sieve plate with the aperture of 0.9mm of an extruder; opening the spheronizer, selecting rotation speed of 1210rpm, placing the strip-shaped objects in the spheronizer, spheronizing for 4min until the particles are rolled into pills, taking out the pellets, drying at 41 ℃, and screening to obtain 9.17kg of pellets of 20-30 meshes.

EXAMPLE 9 preparation of tablets

B. adding water into flos Lonicerae, heating to boil, heat-preserving at 80 deg.C, extracting for 2 times, each for 1 hr, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.18 at 50-60 deg.C, adding ethanol to make ethanol content reach 60%, standing for 24 hr, collecting supernatant, recovering ethanol, concentrating to obtain soft extract with relative density of 1.25 at 50-60 deg.C, vacuum drying, pulverizing, and sieving with 100 mesh sieve to obtain flos Lonicerae extract fine powder for use.

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding microcrystalline fiber and hydroxypropyl fiber (the weight ratio is 4: 3) in a formula amount, uniformly mixing, preparing into coarse granules, drying, crushing, sieving, preparing into granules, drying at low temperature, finishing granules, adding 0.2% of magnesium stearate and 0.1% of talcum powder, uniformly mixing, pressing into 10000 tablets, and coating with a film.

EXAMPLE 10 preparation of capsules

B. adding water into honeysuckle, heating to boil, keeping the temperature at 70 ℃, carrying out hot dipping for 3 times, extracting for 1.5 hours each time, filtering, combining the filtrates, concentrating to obtain clear paste with the relative density of 1.16 at the relative density of 50-60 ℃, adding ethanol to ensure that the ethanol content reaches 70%, standing for 24 hours, taking the supernatant, recovering the ethanol, concentrating to obtain thick paste with the relative density of 1.28 at the relative density of 50-60 ℃, carrying out vacuum drying, crushing, and sieving with a 100-mesh sieve to obtain honeysuckle extract fine powder for later use.

F. and D, mixing the honeysuckle extract fine powder obtained in the step B and the compound extract fine powder obtained in the step E, adding the scorpion fine powder and the angelica fine powder obtained in the step A, uniformly mixing, adding the starch, the micro silica gel powder and the low-substituted hydroxypropyl cellulose (the weight ratio is 3: 2: 1) according to the formula, uniformly mixing, granulating, drying, grading, filling, polishing in a polishing machine, and removing damaged capsules to obtain the traditional Chinese medicine composition.

Claims

1. A traditional Chinese medicine composition for treating rheumatoid arthritis is characterized by being prepared from the following traditional Chinese medicine components:

2. the traditional Chinese medicine composition according to claim 1, which is prepared from the following traditional Chinese medicine components:

3. the traditional Chinese medicine composition according to claim 2, which is prepared from the following traditional Chinese medicine components:

4. an oral solid pharmaceutical preparation comprising the Chinese medicinal composition according to any one of claims 1 to 3.

5. The oral solid pharmaceutical preparation of claim 4, wherein the oral solid pharmaceutical preparation is one of granules, tablets, capsules or pellets.

6. A method of preparing the oral solid pharmaceutical formulation of claim 5, comprising the steps of:

7. The method of claim 6, wherein step B comprises the steps of:

8. The method of claim 6, wherein step D comprises the steps of:

9. Use of the Chinese medicinal composition of any one of claims 1-3 in the preparation of a medicament for treating rheumatoid arthritis.