A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, and raw materials of the traditional Chinese medicine composition include smilax glabra, angelica pubescens, dipsacus asper, rabdosia lophanthoides, corydalis tuber, saposhnicovia divaricata, potentilla discolor, eupatorium fortunei, myrrha and radix clematidis. The traditional "frying" method is integrated into modern double gel preparation, a variety of extraction methods, oil and water-soluble matrix, and medicine and adjuvant are combined in one way, so that an external preparation is prepared, which has the advantages of water-soluble and fat-soluble components, less component loss, high absorption, significant drug effect, and oil and water gel.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine composition, and particularly relates to a traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis and a preparation method. BACKGROUND

[0002] Rheumatoid arthritis (RA) is a chronic, autoimmune disease mainly characterized by inflammatory synovitis, joint swelling, stiffness, and synovial inflammation with cartilage and bone destruction, which can lead to joint deformity and loss of function in severe cases. In addition, RA can also affect organs and systems outside the joints, affecting the normal function of the heart, kidneys, spleen, respiratory system, nervous system, and digestive system, seriously threatening the physical and mental health of patients. RA can shorten the life expectancy of patients, and the main causes of death are extra-articular lesions such as Felty syndrome, rheumatoid heart disease, interstitial nephritis, interstitial pneumonia, depression, and gastrointestinal damage. The global incidence of RA ranges from 0.5% to 1%. In recent years, the prevalence of rheumatoid arthritis has shown an upward trend, and has become a global public health problem. Because the exact cause of RA is not clear, there is no exact treatment for RA, and there is no cure for it. The drugs used to treat RA today are mostly Western medicines, all of which are symptom-relieving and disease-delaying drugs. Commonly used are non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoid drugs (GCs), which have strong anti-inflammatory effects and are frequently used in clinical practice, but have serious side effects such as gastrointestinal reactions, liver and kidney function damage, glucose and lipid metabolism disorders, osteoporosis, femoral head necrosis, gastrointestinal lesions, and infections. Disease-modifying antirheumatic drugs (DMARDs) include methotrexate, which has no obvious analgesic and anti-inflammatory effects, but can control or delay disease progression. Methotrexate is currently used as a first-line anchor drug for the treatment of RA in clinical practice. This drug still has liver damage, nausea, skin rash, diarrhea, hair loss, and oral ulceration. The use of biological agents has raised RA treatment to a new level, significantly improving treatment outcomes. However, the price is high, and the individual economic cost is extremely high. At the same time, biological agents have the risk of exacerbating or inducing infections and tumors. The above commonly used drugs have their own advantages and disadvantages. When a single drug cannot control the progression of RA, multiple drugs are often used in combination, which improves efficacy but also brings more side effects and adverse reactions, and long-term use of patients has poor compliance. Therefore, the clinical treatment needs to expand the RA drugs of various treatment forms, take the advantages of each other, and achieve the purpose of reducing toxicity and increasing efficacy. Traditional Chinese medicine has been used in the treatment of RA for a long time, and has clear syndrome classification and overall regulation, showing a unique advantage. For example, the Chinese medicine prescription Yuebi Jia Shu Decoction, Wutou Decoction, and the Chinese patent drug Wanbi Tablets, as well as external application of traditional Chinese medicine, have been used in the treatment of RA. With the increasing number of RA patients each year, the demand for RA treatment or relief methods and approaches in clinical practice is increasing, and the internal and external use of traditional Chinese medicine for the treatment of RA has become a hot spot in clinical research.Among them, the external treatment method of traditional Chinese medicine can directly reach the lesion in a short time for patients in the onset period, effectively inhibit local arthritis, and avoid the side effects of oral drugs on the gastrointestinal tract, first-pass effect, liver and kidney function damage, femoral head necrosis, adrenal cortex function reduction, osteoporosis, etc. It is suitable for patients in the acute stage of initial or relapse, and can avoid or reduce the use of GCS and NSAIDs. In addition, the external treatment method of traditional Chinese medicine is convenient to use, relatively low in price, and generally accepted by patients, which is one of the optional solutions for treating RA.

[0003] At present, the external preparation for rheumatoid arthritis mainly targets single compounds in chemical drugs or natural drugs, and the proportion of traditional Chinese medicine compound is very small. Due to the characteristics of multi-component, multi-target and multi-path of traditional Chinese medicine, the pharmacodynamic mechanism of traditional Chinese medicine compound preparation is relatively complex, and the factors investigated in the preparation process are quite complicated. The advantages and disadvantages of the preparation process are particularly important for the retention of multi-components of traditional Chinese medicine compound.

[0004] So far, in the existing research and technology of traditional Chinese medicine composition for treating rheumatic diseases, especially in the preparation of external preparations such as double gel and ointment, the preparation process is complex, the loss of medicinal ingredients is too much, the absorption rate is low, and the bioavailability is low, which weakens the clinical efficacy. Therefore, a traditional Chinese medicine composition and preparation method for treating, relieving or preventing rheumatoid arthritis are provided. SUMMARY

[0005] The purpose of the present application is to provide a traditional Chinese medicine composition and preparation method for treating, relieving or preventing rheumatoid arthritis. The traditional "frying" method is integrated into modern double gel preparation, a variety of extraction methods, oil and water-soluble matrix are used, and the method of drug and adjuvant combination is used to prepare an external preparation which takes into account the advantages of water-soluble and lipid-soluble components, less loss of components, high absorption, significant efficacy and the advantages of oil and water gel.

[0006] To solve the above technical problems, the technical scheme adopted by the present application is as follows:

[0007] A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, the raw materials of the traditional Chinese medicine composition include: smilax glabra, angelica pubescens, dipsacus asper, big wind grass, corydalis, saposhnikovia divaricata, rhizoma polygonati, euphorbia, radix clematidis.

[0008] Further, the traditional Chinese medicine composition includes the following components by weight: 10-40 parts of smilax glabra, 10-30 parts of angelica pubescens, 5-15 parts of dipsacus asper, 10-20 parts of big wind grass, 5-15 parts of corydalis, 5-15 parts of saposhnikovia divaricata, 10-20 parts of rhizoma polygonati, 10-20 parts of euphorbia, 1-10 parts of radix clematidis, and 5-15 parts of radix clematidis.

[0009] Further: the traditional Chinese medicine composition includes the following components by weight: 25-35 parts of smilax glabra, 15-25 parts of angelica pubescens, 8-13 parts of dogbane, 12-18 parts of wind grass, 8-13 parts of rhizoma corydalis, 8-13 parts of rhizoma polygonati, 12-18 parts of rhizoma sinodendri, 12-18 parts of radix curculiginis, 3-7 parts of myrrh, 8-13 parts of radix dipsaci.

[0010] Further: the traditional Chinese medicine composition includes the following components by weight: 30 parts of smilax glabra, 20 parts of angelica pubescens, 10 parts of dogbane, 15 parts of wind grass, 10 parts of rhizoma corydalis, 10 parts of rhizoma polygonati, 15 parts of radix dipsaci, 15 parts of radix curculiginis, 5 parts of myrrh, 10 parts of radix dipsaci.

[0011] Further: the preparation method comprises:

[0012] Step 1: weigh the angelica pubescens by weight and fry in soybean oil, take out the angelica pubescens residue, filter to obtain the oil for use;

[0013] Step 2: weigh the smilax glabra, dogbane, wind grass, rhizoma corydalis, rhizoma polygonati, radix dipsaci, radix curculiginis, myrrh and radix dipsaci residue after frying in step 1, mix and crush, sieve to obtain medicinal powder;

[0014] Step 3: take the medicinal powder in step 2 into a container, add 60% ethanol solution, shake well, seal and avoid light;

[0015] Step 4: take the container in step 3 and put it into a water bath, heat, then filter, collect the supernatant in a centrifuge;

[0016] Step 5: take the supernatant in step 4, add it into a rotary evaporator with the temperature set at 65℃, distill under reduced pressure to a thick paste, then send it into a drying oven to dry to a black-brown ointment, the temperature of the drying oven is set at 65℃;

[0017] Step 6: take the ointment in step 5, dissolve it in purified water to a concentration of 1g / ml, which is the test medicinal solution;

[0018] Heat the medicinal oil to 80℃, then add it into glyceryl monostearate while stirring, the mass ratio of glyceryl monostearate to medicinal oil is 4:100, stir evenly to obtain an oil gel solution;

[0019] Step 7: weigh the carbomer, add distilled water, stir, then naturally swell overnight or swell by water bath heating to prepare a carbomer base, then slowly pour the oil gel solution in step 6 into the carbomer base while stirring, then add the test medicinal solution, glycerol, triethanolamine and hydroxyphenyl ethyl alcohol solution in sequence, after adding completely, increase the stirring speed to 1500r / min, stir in the same direction for 10min, after stirring evenly, add distilled water to continue stirring until a fine and uniform double gel is formed.

[0020] Further: in the step 1, the mass ratio of rhizoma angelicae pubescentis and soybean oil is 1:5.

[0021] Further: in the step 2, the residue is mixed and crushed, and then sieved through a 40-mesh sieve;

[0022] In the step 3, 140g of medicinal material powder is added into a container, 2L of 60% ethanol solution is added, and then shaken and sealed to avoid light for 48.

[0023] Further: in the step 4, the container in the step 3 is placed into a water bath with a temperature of 65 DEG C for heating for 30 minutes, and then filtered, and the filtrate is placed into a centrifuge, and the rotating speed is set to 2400r / min. -1

[0024] Further: in the step 7, the mass ratio of the test drug solution, carbomer, triethanolamine, glycerol and water is 15:1:1.2:10:72.8, and the mass fraction of the oil gel is 30%.

[0025] Further: the application of the traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis on liniments and plasters.

[0026] Compared with the prior art, the application has at least one of the following beneficial effects:

[0027] (1) Rhizoma smilacis glabrae, detoxification and dampness, and smooth joints; Rhizoma angelicae pubescentis, expelling wind and dampness, and dredging meridians and collaterals, and relieving arthralgia, and can dispel latent wind in the body, and the two are combined to remove dampness, dredge collaterals and relieve pain as the monarch; Dipsacus asper, tonifying liver and kidney, strengthening tendons and bones, and continuing to repair injuries and stopping metrorrhagia; Aralia cordata, bone-setting, promoting blood circulation and expelling wind and dampness, and it has the effect of "very effective for foot swelling caused by dampness", and the two are combined to expel evil without damaging normal qi, and strengthen tendons and bones as the minister; Corydalis saxicola, pungent and warm, and it is a good medicine for promoting blood circulation and relieving pain, and it is good at treating pains all over the body; Saposhnikovia divaricata, expelling wind and relieving superficies, and it can also stop pain and convulsions; Theyatrum japonicum, expelling wind and dampness, and relaxing muscles and tendons; Rhizoma bletillae, promoting blood circulation and removing blood stasis, and it can also promote urination, remove toxins, and dredge channels and bones, and the above are combined to remove evil and promote blood circulation and dredge collaterals to relieve pain as the assistant; Myrrha, removing blood stasis and relieving pain, and promoting tissue regeneration; Radix Clematidis, expelling wind and dampness, and removing phlegm, and dredging channels and collaterals, and removing stagnation, and the two are combined to promote blood circulation and dredge collaterals as the carrier. The formula mainly removes evil and dredges collaterals to relieve pain, and the medicinal properties are mild, and evil is removed while normal qi is supported, and it can be used regardless of cold, heat, deficiency or excess, and it is safe for external use, and it is targeted for local use, and it can be combined with oral anti-RA drugs to treat both the symptoms and the root cause, and it reduces toxicity and increases efficacy.

[0028] (2) The prepared double gel has the advantages of hydrogel and oil gel, and has good moisturizing property, uniformity and stability, and various extraction methods can well preserve multiple components, and the clinical efficacy is improved.

[0029] ​(3) The present application extracts volatile oil from fried Angelica pubescens and enhances the content of some effective components in the volatile oil, uses the oil after frying as a matrix of oil gel instead of pure soybean oil, and uses the matrix with pharmacological effects to cooperate with the main drug to increase the effect of the main drug and play a better clinical role. At the same time, the volatile oil of Angelica pubescens can also play a role in promoting penetration. After frying Angelica pubescens, the analgesic and anti-inflammatory activity of the whole prescription is greatly improved, and the analgesic and anti-inflammatory effect after frying is the best compared with the two cases without frying. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical scheme and advantages of the present application more clear, the present application is further described in detail below in combination with examples. It should be understood that the specific examples described herein are only used to explain the present application and not to limit the present application.

[0031] I. Screening of Chinese medicine composition

[0032] Example 1:

[0033] A Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis comprises the following components in parts by weight: Smilax glabra 20 parts, Angelica pubescens 25 parts, Dipsacus asper 8 parts, Isodon japonicus 12 parts, Corydalis tuber 13 parts, Saposhnikovia divaricata 13 parts, Pyrrosia lingua 18 parts, Cyperus rotundus 18 parts, Commiphora myrrha 7 parts and Clematis chinensis 12 parts.

[0034] The preparation method is as follows: Angelica pubescens fried with 5 times the amount of soybean oil is taken, the residue is fished out, and the oil is filtered to obtain the oil for use. The other components of the dry Chinese medicine composition are crushed, and the powder passing through a 40-mesh sieve is collected for use. 140 g of the powder is weighed, 2 L of 60% ethanol solution is added, and the mixture is shaken, plugged and cold soaked for 48 h in the dark. Then the conical flask containing the solution is placed in a water bath with a temperature of 65℃ for heating for 30 min. The filtrate is centrifuged at a speed of 2400 r·min -1 -1 for 10 min. The temperature of the rotary evaporator is set to 65℃, and the supernatant is distilled under reduced pressure to a thick paste under the above conditions. Pour the thick paste into a clean flat dish, and place it in a drying oven with a temperature setting of 65℃ until it becomes a black-brown dry paste. Thus, 60% ethanol extract is obtained. A certain amount of 60% ethanol extract is weighed, and purified water is added to prepare a test solution of 1 g / ml for use.

[0035] A certain amount of oil is heated to 80℃, and glyceryl monostearate is added while stirring. The mass ratio of glyceryl monostearate to oil is 4:100. Stir at 80℃ and 500 r / min until the glyceryl monostearate and oil are completely mixed to obtain an oil gel solution.

[0036] Take Carbomer, add distilled water, stir and naturally swell overnight or heat in water bath to swell. After complete swelling, slowly pour the heated and melted oil gel solution into the Carbomer matrix, stirring while pouring, then add appropriate amounts of glycerol, test drug solution, hydroxyethyl benzoate alcohol solution and triethanolamine in sequence. After complete addition, increase the stirring speed to 1500 r / min, and stir in the same direction for 10 min. After uniform stirring, make up with distilled water and continue stirring until a fine and uniform gel is formed. The mass ratio of test drug solution: Carbomer: triethanolamine: glycerol: water is 15:1:1.2:10:72.8, and the mass fraction of oil gel is 30%.

[0037] Example 2

[0038] A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, comprising the following components in parts by weight: Smilax glabra 40 parts, Radix Angelicae Pubescentis 30 parts, Radix Dipsaci 12 parts, Herba Lophatheri 12 parts, Rhizoma Corydalis 12 parts, Radix Saposhnikoviae 15 parts, Herba Sedi 15 parts, Herba Lycopodii 13 parts, Myrrha 4 parts and Radix Trigonellae 8 parts.

[0039] The preparation method is the same as that in Example 1.

[0040] Example 3

[0041] A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, comprising the following components in parts by weight: Smilax glabra 30 parts, Radix Angelicae Pubescentis 30 parts, Radix Dipsaci 12 parts, Herba Lophatheri 10 parts, Rhizoma Corydalis 12 parts, Radix Saposhnikoviae 8 parts, Herba Sedi 15 parts, Herba Lycopodii 20 parts, Myrrha 8 parts and Radix Trigonellae 8 parts.

[0042] The preparation method is the same as that in Example 1.

[0043] Example 4

[0044] A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, comprising the following components in parts by weight: Smilax glabra 30 parts, Radix Angelicae Pubescentis 20 parts, Radix Dipsaci 10 parts, Herba Lophatheri 15 parts, Rhizoma Corydalis 10 parts, Radix Saposhnikoviae 10 parts, Herba Sedi 15 parts, Herba Lycopodii 15 parts, Myrrha 5 parts and Radix Trigonellae 10 parts.

[0045] The preparation method is the same as that in Example 1.

[0046] Comparative Example 1

[0047] A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, comprising the following components in parts by weight: Smilax glabra 30 parts, Radix Angelicae Pubescentis 20 parts, Radix Dipsaci 10 parts, Herba Lophatheri 15 parts, Rhizoma Corydalis 10 parts, Radix Saposhnikoviae 10 parts, Herba Sedi 15 parts, Herba Lycopodii 15 parts, Myrrha 5 parts and Radix Trigonellae 10 parts.

[0048] The preparation method is the same as that in Example 1.

[0049] Comparative Example 2:

[0050] A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, comprising the following components in parts by weight: Smilax glabra 30 parts, Angelica pubescens 20 parts, Eucommia ulmoides 10 parts, Sasa 15 parts, Corydalis 10 parts, Saposhnikovia divaricata 10 parts, Asarum 15 parts, Cyperus 15 parts, Myrrha 5 parts, and Radix Trigonellae 10 parts.

[0051] The preparation method is the same as that of Example 1.

[0052] Comparative Example 3;

[0053] A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, comprising the following components in parts by weight: Smilax glabra 30 parts, Angelica pubescens 20 parts, Eucommia ulmoides 10 parts, Sasa 15 parts, Corydalis 10 parts, Saposhnikovia divaricata 10 parts, Asarum 15 parts, Cyperus 15 parts, Myrrha 5 parts, and Radix Trigonellae 10 parts.

[0054] The preparation method is the same as that of Example 1.

[0055] Comparative Example 4:

[0056] A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, comprising the following components in parts by weight: Smilax glabra 30 parts, Angelica pubescens 20 parts, Eucommia ulmoides 10 parts, Sasa 15 parts, Corydalis 10 parts, Saposhnikovia divaricata 10 parts, Asarum 15 parts, Cyperus 15 parts, Myrrha 5 parts, and Radix Trigonellae 10 parts.

[0057] The preparation method is the same as that of Example 1.

[0058] Test Example:

[0059] Comparison of analgesic activity of different crude drugs

[0060] Ninety healthy ICR mice, half male and half female, were randomly divided into 9 groups, 10 mice in each group, namely a blank control group, an Example 1 group, an Example 2 group, an Example 3 group, an Example 4 group, a Comparative Example 1 group, a Comparative Example 2 group, a Comparative Example 3 group, and a Comparative Example 4 group. Each mouse was depilated on the abdomen to prepare a skin area of 2 cm*3 cm. Except for the blank group, the corresponding double gels were evenly applied to the prepared skin area of each group of mice at 0.5 g per mouse, and were massaged until completely absorbed, covered with gauze, and fixed with medical tape, and the administration was continuously performed for 3 days. Thirty minutes after the last administration, 0.6% acetic acid 0.1 ml / 10 g was injected into the abdominal cavity of each mouse, and the number of writhing times within 15 min was recorded. The inhibition rate of the drug on the writhing reaction was calculated as the evaluation of the analgesic effect of the drug according to the following formula.

[0061]

[0062] The analgesic effect of each example and the prescription of the comparative example was evaluated by taking analgesia as the evaluation index, so as to optimize the best prescription. The experimental results are shown in Table 1.

[0063] Table 1: The writhing of mice in different groups n = 10

[0064]

[0065] Note: compared with the blank control, b P < 0.01.

[0066] From the above data, it can be seen that, compared with the blank group, examples and comparative examples have significant analgesic effect, but from the inhibition rate, the analgesic effect of examples 1-4 is better than that of comparative examples 1-4, and it has better effect on relieving the pain caused by rheumatoid arthritis.

[0067] Comparing comparative example 1 with example 4, the similar effect of smilax is used to replace smilax, and it can be seen from the comparison of the number of writhing of mice that the analgesic effect is obviously weakened after the replacement of the monarch drug smilax. Therefore, it is inferred that after the replacement, the relationship between the drugs in the traditional Chinese medicine composition changes, and the efficacy is poor.

[0068] Comparing comparative example 2 with example 4, the similar effect of eucommia is used to replace eucommia, and it can be seen from the comparison of the analgesic experiment results that the analgesic effect is obviously weakened after the replacement of the ministerial drug eucommia. Therefore, it is inferred that after the replacement, the interaction between eucommia and wind grass weakens the synergistic effect of the monarch drug, and the efficacy is reduced.

[0069] Comparing comparative example 3 with example 4, the similar effect of ligusticum is used to replace wind-preventing, and it can be seen from the comparison of the analgesic experiment results that the analgesic effect is also weakened to a certain extent after the replacement of the auxiliary drug wind-preventing. Therefore, it is inferred that after the replacement, the relationship and restriction between the drugs change, and the efficacy is reduced.

[0070] Comparing comparative example 4 with example 4, the dose of each drug in the prescription is changed, and the relationship between the monarch, minister and auxiliary is changed. After the change of the amount of the drug, the analgesic effect is significantly worse, which breaks the combination relationship of the traditional Chinese medicine composition and reduces the curative effect.

[0071] In summary, the traditional Chinese medicine composition has a reasonable compatibility relationship, and the amount ratio is reasonable, which has a good effect on relieving and treating the pain caused by rheumatoid arthritis. Once the traditional Chinese medicine composition is changed, the efficacy will be discounted, which will affect the clinical curative effect.

[0072] Second, the preparation method of the traditional Chinese medicine composition is screened

[0073] Example 5:

[0074] The preparation method is: take 5 times amount of soybean oil fried Angelica pubescens, fish out the residue, filter to get the oil for use. Dry the other components of the composition of traditional Chinese medicine composition and Angelica pubescens fried residue is crushed, collect the powder through 40 mesh sieve, for standby. Take 140g of the powder, add 2L of 60% ethanol solution, shake well, seal, avoid light, and soak for 48h. Then put the conical flask containing the solution into a water bath with temperature of 65℃ for 30min, filter, centrifuge the filtrate in a centrifuge with speed of 2400r·min -1 , centrifuge for 10min. Set the temperature of rotary evaporator to 65℃, and distill the supernatant under reduced pressure to thick paste under this condition, pour into a clean flat dish, put into a drying oven with temperature setting of 65℃, and dry to black brown dry paste, then get 60% ethanol extract. Take a certain amount of 60% ethanol extract, and dissolve in purified water to get 1g / ml test solution for standby.

[0075] Take a certain amount of oil and heat to 80℃, while stirring, add glyceryl monostearate, the mass ratio of glyceryl monostearate to oil is 4:100, stir at 80℃ and 500r / min until the glyceryl monostearate and oil are completely mixed, and get oil gel solution.

[0076] Take carbomer, add distilled water, stir and swell naturally overnight or swell by water bath heating. After complete swelling, slowly pour the heated and melted oil gel solution into the carbomer matrix, stir while pouring, then add appropriate amount of glycerol, test solution, hydroxyphenyl ethyl alcohol solution and triethanolamine in turn, after complete addition, increase the stirring speed to 1500r / min, stir for 10min along the same direction, after uniform stirring, add distilled water to make up, continue to stir until a fine and uniform gel is formed. The mass ratio of test solution: carbomer: triethanolamine: glycerol: water is 15:1:1.2:10:72.8, and the mass fraction of oil gel is 30%.

[0077] Example 6

[0078] The preparation method is the same as that of example 5, the difference is that Angelica pubescens in the composition is not fried, the whole composition is directly crushed to prepare 60% ethanol extract, and the remaining steps are the same.

[0079] Example 7

[0080] The preparation method is the same as that of example 5, the difference is that Angelica pubescens in the composition is not fried, the whole composition is directly crushed to prepare 60% ethanol extract, and 1% azone is added during the final mixing and stirring, and the remaining steps are the same.

[0081] Test example

[0082] 1 Comparison of analgesic activity of different crude drugs

[0083] Take 40 healthy ICR mice, half male and half female, and randomly divide them into 4 groups, 10 mice in each group, namely the blank control group, Example 1 group, Example 2 group, and Example 3 group. Each group of mice is depilated on the abdomen, and the depilation area is 2 cm*3 cm. Except for the blank group, each group evenly applies 0.5 g of the corresponding double gel to the depilation area of the mice, massages it until it is completely absorbed, covers gauze, and fixes it with medical tape, and continuously administers it for 3 days. 30 min after the last administration, each mouse is injected with 0.6% ice acetic acid 0.1 ml / 10 g intraperitoneally, and the number of writhing times within 15 min is recorded. The inhibition rate of the drug on the writhing reaction is calculated as the evaluation of the analgesic effect of the drug according to the following formula.

[0084]

[0085] 2 Comparison of anti-inflammatory activities of different crude materials

[0086] 2.1 Acute inflammation

[0087] 2.1.1 Modeling and administration

[0088] Take 50 healthy ICR mice, half male and half female, and randomly divide them into 5 groups, 10 mice in each group, namely the blank control group, the model group, Example 1 group, Example 2 group, and Example 3 group. Except for the blank group and the model group, each group of rats is applied with 0.5 g of different double gels on the right ankle joint to the toes every day, massages it until it is absorbed, covers gauze, and fixes it with medical tape, once a day, continuously for 7 days. 1 h after the last administration, immediately inject 1% carrageenan solution 0.02 mL into the right hind foot skin of each group of mice to cause inflammation;

[0089] 2.1.2 Detection index

[0090] The mice are sacrificed by cervical dislocation 2 h after the inflammation, and the right and left feet are cut off at the same site, and the mass is weighed to calculate the mouse foot swelling degree and swelling inhibition rate. Foot swelling degree = right foot (mg) - left foot (mg), swelling inhibition rate (%) = (model group - administration group) / model group x 100%.

[0091] 2.2 Rheumatoid arthritis

[0092] 2.2.1 Modeling and administration

[0093] 60 SD rats were randomly divided into blank control group, model group, positive control Voltaren group, Example 1 group, Example 2 group, Example 3 group, 10 rats in each group. Except the normal group, the other groups of mice were injected with emulsified collagen-adjuvant emulsion under the tail root subcutaneously, 0.1 mL (containing protein 100 μg) per mouse. The first immunization was recorded as day 0, and the above steps were repeated on day 21 for the second time. The modeling was started on the 14th day, and different drugs were given to the rest of the groups, 0.5 g per mouse, which was evenly applied around the right ankle joint of the rat, and the drug was fully absorbed by gently massaging for several times, covered with gauze, and fixed with medical tape, once a day. The blank group and the model group were given normal saline according to the body weight, and the continuous administration was 28 days. 2.2.2 Determination of TNF-α and IL-1β levels in serum

[0094] One hour after the last administration, the rats were anesthetized with 10% chloral hydrate solution, blood was taken from the common carotid artery, and the upper plasma was obtained by centrifugation. The levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in the plasma of each group of rats were determined using an ELISA kit. The ELISA kit uses a double antibody sandwich method to determine the levels of rat TNF-α and IL-1β in the sample. The basic principles of the two are the same. According to the standard steps of the ELISA kit, the OD value is finally determined. The standard curve is prepared, and the concentration of TNF-α or IL-1β in the test solution is obtained by the standard curve.

[0095] 2.3 Results

[0096] As shown in Table 2, the analgesic activity of Examples 1, 2 and 3 was significantly different from that of the blank group, and the analgesic effect was obvious (P<0.05). In terms of writhing inhibition rate, Example 1>Example 3>Example 2, and Example 1 had the best analgesic effect. In terms of analgesia, the gel preparation method of Example 1 was the best.

[0097] As shown in Table 3, compared with the blank group, the foot swelling of the model group was significantly reduced (P<0.05); compared with the model group, the foot swelling of each administration group was significantly reduced (P<0.05), and the anti-inflammatory effect was significant. In terms of swelling inhibition rate, Example 1>Example 3>Example 2.

[0098] Table 4 shows that in the rheumatoid arthritis animal model, the model group was significantly higher than the blank group in the content of IL-1β and TNF-α in serum; compared with the model group, the content of IL-1β and TNF-α in serum of Examples 1, 2 and 3 was significantly reduced, and the difference was significant (P<0.05). In terms of the degree of reduction, Example 1>Example 3>Example 2. In combination with Table 2 and Table 3, in terms of anti-inflammatory effect, the gel preparation method of Example 1 was the best.

[0099] Through the activity screening of analgesic anti-inflammatory experiment, it is concluded that the gel preparation method of example 1 has obvious promotion effect on the clinical effect of the prescription.

[0100] Table 2 writhing of mice in different groups n=10

[0101]

[0102] Note: compared with the blank control, a / b P<0.05 / 0.01.

[0103] Table 3 effect of gels with different treatments on the swelling of acute inflammatory feet of mice n=10

[0104]

[0105] Note: compared with the blank group, ap≤0.01; compared with the model group, bp≤0.05, cp≤0.01.

[0106] Table 4 effect of different extracts on serum inflammatory factors of rats n=10

[0107]

[0108] Note: compared with the blank group, ap≤0.01; compared with the model group, bp≤0.05, cp≤0.01.

[0109] Innovations: The main medicine of the prescription is Angelica pubescens, which has rich volatile oil. The volatile oil and the content of part of the effective components in the volatile oil are extracted by frying Angelica pubescens, and the oil after frying is used to replace pure soybean oil as the matrix of the oil gel. The matrix with pharmacological effect is combined with the main medicine to increase the effect of the main medicine and play a better clinical role. At the same time, the volatile oil of Angelica pubescens can also play a role in promoting penetration. Compared with example 7, example 6 does not add a penetration enhancer, but the pharmacological effect of the double gel is stronger. Compared with example 7, example 5 does not add a penetration enhancer, but the pharmacological effect is not weaker than example 7. On the contrary, the pharmacological effect of example 5 is better than that of example 7, which shows that the oil not only strengthens the effect of the main medicine, but also has a certain penetration-promoting effect.

[0110] While the application has been described with reference to numerous exemplary embodiments, it will be understood that various other modifications can be made within the scope of the application as disclosed herein. More particularly, many modifications can be made to the components and / or arrangements of the subject combinations within the scope and spirit of the disclosure and claims. In addition those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. It is therefore to be understood that any embodiments disclosed herein are merely illustrative of the principles of the present application and that various modifications can be made by those skilled in the art which will accomplish like results.

Claims

1. A traditional Chinese medicine composition for treating, relieving or preventing rheumatoid arthritis, characterized in that: The raw materials of the traditional Chinese medicine composition are composed of the following components in parts by weight: 10-40 parts of smilax glabra, 10-30 parts of angelica pubescens, 5-15 parts of dipsacus asper, 10-20 parts of isodon japonicus, 5-15 parts of rhizoma corydalis, 10-20 parts of rhizoma polygonati, 10-20 parts of radix saposhnikoviae, 1-10 parts of myrrha, and 5-15 parts of radix dipsaci; ​ The preparation method of the traditional Chinese medicine composition comprises the following steps: Step 1: The angelica pubescens is weighed in parts by weight and fried in soybean oil, and the angelica pubescens residue is filtered to obtain medicinal oil for use; Step 2: The smilax glabra, dipsacus asper, isodon japonicus, rhizoma corydalis, radix saposhnikoviae, radix polygonati, radix dipsaci, myrrha and radix dipsaci fried in step 1 are mixed and crushed, and the crushed mixture is sieved to obtain medicinal powder; Step 3: The medicinal powder in step 2 is taken into a container, and ethanol solution is added, and the container is sealed and shaken and then soaked in dark place; Step 4: The container in step 3 is taken out and placed in a water bath, and then filtered, and the filtrate is collected in a centrifuge to obtain supernatant; Step 5: The supernatant in step 4 is taken and placed in a rotary evaporator, and distilled under reduced pressure until it becomes thick, and then dried in a drying box until it becomes black-brown medicinal paste for use; Step 6: The medicinal paste in step 5 is taken and dissolved in purified water to obtain a medicinal liquid with a concentration of 1 g / ml, which is the test medicinal liquid; the medicinal oil is heated to 80 DEG C, and then glyceryl monostearate is added while stirring, and the mass ratio of glyceryl monostearate to medicinal oil is 4:100, and then the oil gel solution is obtained; Step 7: Carbomer is weighed and added into distilled water, and then stirred and naturally swelled overnight or swelled by water bath heating to obtain a carbomer matrix, and then the oil gel solution in step 6 is slowly poured into the carbomer matrix while stirring, and then the test medicinal liquid, glycerol, triethanolamine and hydroxyphenyl ethyl alcohol solution are sequentially added, and then the stirring speed is increased to 1500 r / min along the same direction until a fine and uniform double gel is formed.

2. The traditional Chinese medicine composition according to claim 1, characterized in that: The raw materials of the traditional Chinese medicine composition are composed of the following components in parts by weight: 25-35 parts of smilax glabra, 15-25 parts of angelica pubescens, 8-13 parts of dipsacus asper, 12-18 parts of isodon japonicus, 8-13 parts of rhizoma corydalis, 8-13 parts of radix saposhnikoviae, 12-18 parts of radix polygonati, 12-18 parts of myrrha, and 8-13 parts of radix dipsaci.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The raw materials of the traditional Chinese medicine composition are composed of the following components in parts by weight: 30 parts of smilax glabra, 20 parts of angelica pubescens, 10 parts of dipsacus asper, 15 parts of isodon japonicus, 10 parts of rhizoma corydalis, 10 parts of radix saposhnikoviae, 15 parts of radix polygonati, 15 parts of myrrha, and 10 parts of radix dipsaci.

4. The traditional Chinese medicine composition according to claim 1, characterized in that: In step 1, the mass ratio of angelica pubescens to soybean oil is 1:

5.

5. The traditional Chinese medicine composition according to claim 1, characterized in that: In step 2, the residue is crushed and sieved through a 40-mesh sieve; In step 3, the medicinal powder is taken into a container, 60% ethanol solution is added, and the container is sealed and shaken and then soaked in dark place for 48 hours. In step 3, the medicinal powder is taken into a container, 60% ethanol solution is added, and the container is sealed and shaken and then soaked in dark place for 48 hours.

6. The traditional Chinese medicine composition according to claim 1, characterized in that: In step 4, the container in step 3 is placed in a water bath at 65°C for 30 min, then filtered, and the filtrate is placed in a centrifuge at a speed of 2400 r / min for 10 min. -1 , centrifuged at 2400 r / min for 10 min.

Images