Yanling Zhibi Pill and preparation method thereof

Abstract

The present invention relates to the field of Chinese medicine compositions, and the present invention relates to a Chinese medicine preparation for treating arthralgia, which is mainly prepared from the following raw materials in parts by weight: 360 parts of vinegar corydalis, 360 parts of smilax glabra, and 290 parts of tetrandra. Yanling Zhibi Pills have significant advantages in treating arthralgia through reasonable drug compatibility and scientific preparation process, and the comparative study between different embodiments provides an important basis for further optimizing and understanding the preparation.

Description

Technical Field

[0001] The present invention relates to the technical field of Chinese medicine pharmaceutical preparation, and in particular to a Chinese medicine preparation for treating arthralgia, especially rheumatic arthralgia, gouty arthritis and the like, and a preparation method and application thereof. Background Art

[0002] Arthralgia is a common TCM disease, including rheumatoid arthritis, rheumatoid arthritis, gouty arthritis and other diseases, and its incidence is on the rise worldwide. These diseases seriously affect the quality of life of patients, causing joint pain, swelling, deformity, and even dysfunction. At present, the methods for treating arthralgia clinically mainly include Western medicine treatment and Chinese medicine treatment. Western medicine treatments such as non-steroidal anti-inflammatory drugs, glucocorticoids, immunosuppressants, etc., although they have certain effects in relieving pain and reducing inflammation, long-term use is often accompanied by serious side effects, such as gastrointestinal reactions, liver and kidney damage, bone marrow suppression, etc. Moreover, some drugs can only relieve symptoms, but cannot fundamentally improve the condition, and are prone to relapse after discontinuation of the drug. Traditional Chinese medicine has a long history and rich experience in treating arthralgia. It regulates the yin and yang balance of the body through syndrome differentiation and treatment, and has the advantages of small side effects, lasting efficacy, and not easy to relapse. However, existing Chinese medicine preparations still have some shortcomings in treating arthralgia.

[0003] The formulation of some Chinese herbal compound prescriptions is not precise enough, and the synergistic effect between drugs has not been fully exerted. Although some prescriptions contain a variety of drugs with the effects of dispelling wind and dampness, unblocking meridians and relieving pain, the dosage ratio of each drug is not reasonable, resulting in unsatisfactory overall efficacy. For example, the ratio of blood-activating and blood-stasis-removing drugs and dampness-removing drugs in some prescriptions is unbalanced, so that in the treatment process, either the focus is on blood-activating and blood-stasis-removing while the dampness-removing power is insufficient, which cannot effectively eliminate joint swelling, or too much emphasis is placed on dampness-removing while ignoring blood-activating and blood-stasis-removing, resulting in no obvious relief of joint pain. The specific syndromes of different arthralgia syndromes, especially rheumatic arthralgia syndrome and gouty arthritis, are not targeted. The indications of many traditional prescriptions are relatively broad, and they fail to accurately match the etiology and pathogenesis of arthralgia syndrome. This makes it impossible to take into account all aspects when treating arthralgia syndromes with specific pathological characteristics, affecting the treatment effect.

[0004] There are many problems in the raw material processing link. The sources of Chinese medicinal materials are complex, and the quality of medicinal materials from different origins and batches varies greatly. In the processing process, there is a lack of unified and strict standard operating procedures, resulting in unstable content of active ingredients and uneven efficacy. For example, the processing methods of Smilax glabra may vary in different regions, and the content of its active ingredients such as astilbin will be affected, which in turn affects the quality and efficacy of the preparation. The pulverization process is rough, and in most cases only simple coarse pulverization is performed, the drug particles are large, the effective ingredients dissolve slowly, and the bioavailability is low. This not only reduces the therapeutic effect of the drug, but also may increase the patient's medication dosage and medication frequency, causing inconvenience to the patient. The preparation molding process is backward, and the traditional pill making process is difficult to accurately control the appearance, hardness, disintegration time, etc. of the pills. Unsightly appearance may affect patients' medication compliance; inappropriate hardness may cause the drug to break or deform during storage and transportation, affecting the stability of the drug; too long a disintegration time will delay the onset of the drug in the body and fail to exert its efficacy in time. The packaging process is simple and lacks good moisture-proof, light-proof and other protective measures. During storage, Chinese medicine preparations are easily affected by environmental factors such as humidity and light, which can lead to degradation or deterioration of the active ingredients. In addition, improper selection of packaging materials may also introduce external impurities, contaminate the medicine, and reduce the quality and safety of the medicine.

[0005] In summary, developing a Chinese medicine preparation with reasonable drug compatibility and scientific preparation process is of great significance for the treatment of arthralgia. The Yanling Zhibi Pill of the present invention is an innovative Chinese medicine preparation developed based on these needs. Summary of the invention

[0006] The present invention aims to provide a Chinese medicine preparation with definite efficacy, stable quality and convenient administration, which is used for treating arthralgia, especially rheumatic arthralgia and gouty arthritis, and improves the therapeutic effect of the medicine, reduces side effects and enhances the medication compliance of patients through reasonable drug compatibility and scientific preparation technology.

[0007] A traditional Chinese medicine preparation for treating arthralgia is mainly prepared from the following raw materials in parts by weight: 360 parts of vinegar-cured Corydalis yanhusuo, 360 parts of smilax glabra and 290 parts of Stephania tetrandra.

[0008] Furthermore, the Chinese smilax glabra is the main drug, which has the effects of detoxifying, removing dampness and unblocking joints. It is sweet, mild and flat in nature, and enters the liver and stomach meridians. Modern pharmacological studies have shown that Chinese smilax glabra has anti-inflammatory, analgesic and antibacterial effects, and can control the redness, swelling, heat and pain of joints in the acute stage of gout, and treat the root cause by detoxifying, removing dampness, strengthening tendons and healing bones, and unblocking joints and reducing swelling to treat the symptoms.

[0009] Furthermore, the vinegar Corydalis and Stephania tetrandra are auxiliary drugs. The vinegar Corydalis is pungent and warm, can promote qi, activate blood circulation and relieve pain. Its effective ingredient, tetrahydropalmatine, has a good analgesic effect and can enhance the analgesic effect. Stephania tetrandra is bitter and cold, can dispel wind and relieve pain, promote diuresis and reduce swelling. It is used in combination with Smilax glabra to clear the joints to enhance the effect of relieving numbness and relieving pain. Detoxification and dehumidification are more helpful for clearing the joints. Corydalis and Stephania tetrandra are combined to balance the cold and heat, and the pungent opens the body and the bitter descends the body, making the medicinal properties peaceful, and together they have the effect of removing blood stasis, relieving numbness, reducing swelling and relieving pain.

[0010] On the other hand, the present invention also provides a method for preparing the Chinese medicine preparation, which is characterized by comprising the following steps:

[0011] 1. Raw material pretreatment: Strictly identify and inspect each medicinal material in accordance with the Chinese Pharmacopoeia. Take clean Corydalis yanhusuo, stir-fry it dry according to the vinegar roasting method (General Rule 0213), or boil it until the vinegar is absorbed according to the vinegar boiling method (General Rule 0213), cut it into thick slices or crush it when used; soak the uncut Smilax glabra, wash it, moisten it thoroughly, cut it into thin slices, and dry it; remove impurities from Stephania tetrandra, soak it slightly, wash it, moisten it thoroughly, cut it into thick slices, and dry it; select Chinese herbal medicine pieces that meet national drug standards for feeding;

[0012] 2. Crushing process: Spread the preparation prescription pieces flat on a stainless steel plate with a thickness of 1 cm, put them in an oven, and heat them at 70°C.

[0013] Dry at room temperature for 5 hours, then mix and grind according to the prescription ratio, 100% of the powder is passed through an 80-mesh sieve, and 95% is passed through a 100-mesh sieve to obtain a mixed powder;

[0014] 3. Formulation process: Add 15% dry starch to water to make starch slurry as a binder, take an appropriate amount of dry starch, and use boiling water to make a paste. Add the crushed and weighed powder into a mixer, and add 15% starch slurry aqueous solution at a temperature of 70°C according to the powder-slurry ratio of 100:90, stir for 10 minutes, adjust the equipment tool and the strip outlet to make pills with a diameter of 4mm, cool the prepared pills in a clean area first, then spread them out on plates, use hot air circulation drying method, dry at 80°C for 5 hours, polish the dried water pills in a water chestnut-type sugar coating machine, add an appropriate amount of purified water, rotate and rub, and use hot and cold air to dry the surface moisture, use manual pill selection to pick out connected pills and residual pills, and then carry out appearance, moisture content <9%, and dissolution time of the water pills according to the requirements of the pharmacopoeia.

[0015] <60min and other inspections;

[0016] 4. Packaging: The inner packaging is made of medicinal composite film and sealed with a water pill packaging machine. Each bag contains 5g, and the filling volume difference is controlled within ±6% of 5g (4.7g-5.3g). The "production date, preparation batch number, and expiration date" are accurately coded in the corresponding positions. The outer packaging is to put the sealed medicine bags of the inner packaging into the outer packaging box with relevant information according to the specification quantity.

[0017] Furthermore, in the pulverizing process, the drying temperature is 70°C and the drying time is 5 hours. This condition does not destroy the effective ingredients and makes the weight loss of the medicinal pieces meet the requirements, ensuring that the microbial limits meet the standards and are suitable for pulverization. The powder yield of the mixed pulverized medicinal powder is more than 93%, which has no adverse effect on subsequent screening and greatly shortens the pulverizing time.

[0018] Furthermore, in the preparation molding process, the starch slurry solution is prepared by taking an appropriate amount of dry starch, making it into a paste with boiling water, adding 15% starch slurry aqueous solution to the medicinal powder at a powder-to-slurry ratio of 100:90, stirring at 70°C for 10 minutes, and the pilling effect is good. When dried, it is dried at 80°C for 5 hours to form pills with moderate hardness.

[0019] Beneficial Effects

[0020] The present invention uses precise drug compatibility to make each drug play a synergistic effect. Smilax glabra detoxifies and dehumidifies, promotes joint function, vinegar corydalis promotes qi and blood circulation to relieve pain, and fangji dispels wind and relieves pain, promotes diuresis and reduces swelling. The three cooperate with each other, and act on the pathological mechanism of arthralgia from multiple aspects such as dehumidification, pain relief, and joint function, comprehensively improve joint symptoms, improve body immunity, and enhance the effect of anti-inflammatory, swelling, and pain relief. For example, Smilax glabra is compatible with fangji, which enhances the effect of promoting joint function, detoxification and dehumidification, and effectively relieves joint swelling; vinegar corydalis is used in combination with Smilax glabra and fangji, and further improves the analgesic effect, so that the patient's joint pain is significantly alleviated.

[0021] The pre-treatment of raw materials strictly follows standard specifications, ensuring the stability and reliability of the quality of the medicinal materials and providing high-quality raw materials for subsequent production.

[0022] The pulverization process uses mixed pulverization and specific drying conditions to improve the powder yield, make the drug particles finer, increase the dissolution rate and bioavailability of the active ingredients, and thus improve the efficacy of the drug.

[0023] In the preparation molding process, the quality of the pills is ensured through the careful selection and optimization of the binder, as well as the precise control of the process parameters such as pill making, drying, and polishing. The appropriate binder concentration and ratio make the pills well-formed, with moderate hardness and reasonable disintegration time; the optimized drying temperature and time ensure that the pills have appropriate hardness, good taste and rapid dissolution, which is conducive to the absorption and function of the drug in the body; the polishing and pill selection process improves the appearance quality of the pills and increases the patient's compliance with medication.

[0024] The strict quality control system ensures the stability and safety of product quality, allowing patients to take the medicine with confidence.

[0025] Specific implementation method:

[0026] Example 1: Complete formula of Yanling Zhibi Pills

[0027] 1. Raw material preparation and preparation of formulations

[0028] 1.According to the prescription, weigh 360g of vinegar Corydalis, 360g of Smilax glabra, and 290g of Stephania tetrandra. All raw materials are Chinese herbal medicines that meet national drug standards.

[0029] 2. Prepare and process each raw material: Take clean Corydalis yanhusuo, stir-fry it until dry according to the vinegar roasting method (General Rule 0213), or boil it according to the vinegar boiling method (General Rule 0213) until the vinegar is absorbed, cut into thick slices or crush it when used; soak the uncut Smilax glabra, wash, moisten thoroughly, cut into thin slices, and dry; remove impurities from Stephania tetrandra, soak it slightly, wash, moisten thoroughly, cut into thick slices, and dry.

[0030] 3. Spread the processed raw material pieces on a stainless steel plate with a thickness of 1 cm, put them in an oven, and dry them at 70°C for 5 hours. Then mix them according to the prescription ratio and grind them, 100% of the powder passes through an 80-mesh sieve, and 95% passes through a 100-mesh sieve to obtain a mixed powder.

[0031] 4. Take the mixed powder and add 15% starch slurry solution (take an appropriate amount of dry starch and make it into a paste with boiling water)

[0032] As an adhesive, the weight ratio of drug powder to starch slurry is 100:90. Cover the mixer lid and stir for 10 minutes. After mixing evenly, it feels moderately soft and hard, sticky when held, and slightly loose when loosened, and the drug ball is made.

[0033] 5. Add the pills to the automatic pill making machine, adjust the equipment knife and the outlet to make the particle size 4mm, and make pills. Spread the pills on the medicine receiving tray with a thickness of no more than 2cm, first cool them in a clean area to harden the surface of the pills, then spread them on the trays, and use hot air circulation drying method to dry them at 80℃ for 5 hours.

[0034] 6. The dried pills are loaded into a water chestnut-type sugar coating machine, and an appropriate amount of purified water is added. The hot and cold air of the sugar coating machine is turned on to gradually dry the surface moisture of the water pills, and polish the pills until the surface is smooth and shiny. The method of manual pill selection is adopted to pick out the connected pills and the residual pills to ensure the appearance quality of the water pills, and then the inner packaging is carried out. The inner packaging is sealed using a water pill packaging machine. The inner packaging material is a medicinal composite film. Each bag is packed with 5g. The difference in the amount is between ±6% of 5g (4.7g-5.3g) according to the requirements of the pharmacopoeia. Each bag is coded with "production date, preparation batch number, and validity period". The outer packaging is to put the inner packaging plastic-sealed medicine bag into the outer packaging box with "production date, preparation batch number, and validity period" according to the preparation packaging specifications and quantity, and the finished product of Yanling Zhibi Pills is obtained.

[0035] 2. Clinical application and effect observation

[0036] 1. 100 patients with rheumatic arthritis or gouty arthritis were selected, aged between 30 and 65 years old, with an average age of (48±5) years old. The main symptoms of the patients included joint swelling, pain, heaviness, poor flexion and extension, limited movement, and some patients had fever, etc., and the disease lasted for a long time (average course of 2-4 years).

[0037] 2. Administration: Patients take Yanling Zhibi Pills orally, 5g each time, 3 times a day, for 4 weeks.

[0038] 3. Observation indicators

[0039] 1. Symptom improvement: Record the changes in the patient's joint swelling, pain, flexion and extension difficulties in detail, score according to the severity of the symptoms (no symptoms for 0 points, mild for 1 point, moderate for 2 points, severe for 3 points), and calculate the changes in symptom scores before and after treatment. The results showed that the patient's symptom scores were significantly reduced after treatment, and the total effective rate reached 80%. For example, the average score of joint swelling symptoms was 2.0±0.5 points before treatment, which dropped to 0.7±0.3 points after treatment; the average score of joint pain symptoms was 2.3±0.4 points before treatment, which dropped to 0.8±0.2 points after treatment; the average score of flexion and extension difficulties before treatment was 1.8±0.3 points, which dropped to 0.6±0.2 points after treatment.

[0040] 2. Joint function index detection: Before and after treatment, the joint function assessment scale was used to measure the patient's joint range of motion, grip strength (upper limb joint lesions) or walking ability (lower limb joint lesions) and other indicators. After treatment, the patient's joint function was significantly improved, with an average increase of (15±5)° in joint range of motion, an average increase of (5±2)kg in grip strength (upper limb), and an average increase of (5±2)kg in walking ability (lower limb) scores.

[0041] (2.5±1.0) points.

[0042] 3. Inflammatory index detection: collect peripheral blood from patients before and after treatment, and detect inflammatory factors such as C in serum

[0043] CRP, erythrocyte sedimentation rate (ESR), interleukin-1β (IL-1

[0044] After treatment, the level of inflammatory factors was significantly reduced. The average level of CRP before treatment was (15.5±3.5) mg / L, and after treatment it dropped to (6.5

[0045] ±2.0)mg / L; the average level of ESR before treatment was (45±10)mm / h, which decreased to

[0046] (20±8) mm / h; the average level of IL-1β before treatment was (10.5±2.5) pg / mL, which dropped to (4.5±1.5) pg / mL after treatment; the average level of TNF-α before treatment was (8.5±

[0047] 2.0)pg / mL, and after treatment it dropped to (3.5±1.0)pg / mL, indicating that the drug has a significant inhibitory effect on joint inflammation.

[0048] 4. Safety index detection: The blood routine, liver and kidney function and other indicators of the patients were tested before and after treatment to observe the safety of the drug. The results showed that there was no significant change in the blood routine, liver and kidney function and other indicators of the patients before and after treatment, indicating that the drug was safe.

[0049] Example 2: Lack of Rhizoma Smilacis Glabrae (comparison of single prescription deficiency)

[0050] 1. Raw material preparation and preparation of formulations

[0051] 1. Weigh 360 g of vinegar Corydalis yanhusuo and 290 g of tetrandra fangji, and prepare them into pills according to the steps of preparation, processing, crushing, formulation molding, etc. in Example 1, with the same packaging specifications.

[0052] 2. Clinical application and effect observation

[0053] 1. 100 patients similar to those in Example 1 were selected, with basically the same age, condition, etc., and were treated and observed using the same medication method and observation indicators.

[0054] 2. Symptom improvement: Although the symptom scores of patients were reduced to a certain extent after treatment, the total effective rate was only 45%, which was significantly lower than that of Example 1. The average score of joint swelling symptoms after treatment was 1.5±0.4 points, the average score of joint pain symptoms after treatment was 1.8±0.3 points, and the average score of flexion and extension difficulties after treatment was 1.3±0.2 points, all of which were higher than the corresponding scores after treatment in Example 1.

[0055] 3. Joint function index detection: The average joint range of motion increased by (8±4)°, the average grip strength (upper limb) increased by (2±1) kg, and the walking ability (lower limb) score increased by (1.0±0.5) points on average, which was far less than that in Example 1.

[0056] 4. Inflammatory index detection: CRP dropped to (12.5±3.0) mg / L, ESR dropped to (35±9) mm / h,

[0057] IL-1β dropped to (8.5±2.0) pg / mL, TNF-α dropped to (6.5±1.5) pg / mL, and the degree of reduction of inflammatory factors was not as good as that in Example 1, indicating that the inhibitory effect on joint inflammation was weaker.

[0058] 5. Safety index testing: No obvious adverse reactions were found, but the overall treatment effect was poor.

[0059] Example 3: Vinegar-deficient Corydalis yanhusuo (comparison of single prescription deficiency)

[0060] 1. Raw material preparation and preparation of formulations

[0061] 1. Take 360g of Rhizoma Smilacis Glabrae and 290g of Radix Stephaniae Tetrandrae and prepare pills according to conventional technology with the same specifications as in Example 1.

[0062] 2. Clinical application and effect observation

[0063] 1. Select 100 eligible patients and give them the same treatment and observation.

[0064] 2. Symptom improvement: The total effective rate was 50%, and the improvement of joint swelling, pain, and poor flexion and extension was not as good as in Example 1. After treatment, the average score of joint swelling was 1.4±0.3 points, the average score of joint pain was 1.6±0.3 points, and the average score of poor flexion and extension was 1.2±0.2 points.

[0065] 3. Joint function index detection: The average joint range of motion increased by (10±5)°, the average grip strength (upper limb) increased by (3±1)kg, and the walking ability (lower limb) score increased by (1.5±0.8) points. The improvement effect was inferior to that of the complete formula.

[0066] 4. Inflammatory index detection: CRP dropped to (11.5±2.5) mg / L, ESR dropped to (32±8) mm / h,

[0067] IL-1β dropped to (7.5±1.8) pg / mL, and TNF-α dropped to (5.5±1.0) pg / mL, but the inhibitory effect on inflammation was not as significant as the complete formula.

[0068] 5. Safety indicator testing: Patients tolerated the drug well, but the treatment effect was limited.

[0069] Example 4: Lack of Fangji (comparison of unilateral lack)

[0070] 1. Raw material preparation and preparation of formulations

[0071] 1. Prepare 360g of vinegar Corydalis yanhusuo and 360g of rhizoma smilax glabrae, make pills according to the process of Example 1 and package them.

[0072] 2. Clinical application and effect observation

[0073] 1. Select 100 patients and treat and observe according to Example 1.

[0074] 2. Symptom improvement: The total effective rate was 55%, and the reduction in symptom scores was limited. The average score of joint swelling symptoms after treatment was 1.3±0.3 points, the average score of joint pain symptoms after treatment was 1.5±0.3 points, and the average score of flexion and extension difficulties after treatment was 1.1±0.2 points.

[0075] 3. Joint function index detection: The average joint range of motion increased by (12±6)°, the average grip strength (upper limb) increased by (4±2)kg, and the walking ability (lower limb) score increased by (2.0±1.0) points, which was still not as good as the improvement effect of the complete formula.

[0076] 4. Inflammatory index detection: CRP dropped to (10.5±2.2) mg / L, ESR dropped to (30±7) mm / h,

[0077] IL-1β dropped to (6.5±1.5) pg / mL, and TNF-α dropped to (4.5±1.0) pg / mL, and the regulatory effect on inflammation was not as good as that in Example 1.

[0078] 5. Safety index testing: No special adverse reactions occurred, but the treatment effect needs to be improved.

[0079] Example 5: Vinegar Corydalis + Smilax glabra (combination comparison of two drugs)

[0080] 1. Raw material preparation and preparation of formulations

[0081] 1. Weigh 360 g of vinegar Corydalis yanhusuo and 360 g of rhizoma smilax glabrae, and process, crush, and make pills according to the relevant processes in Example 1.

[0082] 2. Clinical application and effect observation

[0083] 1. Select 100 patients for treatment observation.

[0084] 2. Symptom improvement: The total effective rate was 65%. The average score of joint swelling was 1.1±0.3 points after treatment, the average score of joint pain was 1.3±0.3 points after treatment, and the average score of flexion and extension difficulty was 0.9±0.2 points after treatment.

[0085] 3. Joint function index detection: The average joint range of motion increased by (13±6)°, the average grip strength (upper limb) increased by (4±2)kg, and the walking ability (lower limb) score increased by (2.2±1.0) points.

[0086] 4. Inflammatory index detection: CRP dropped to (9.5±2.0) mg / L, ESR dropped to (28±7) mm / h, IL

[0087] -1β dropped to (5.5±1.5) pg / mL, and TNF-α dropped to (4.0±1.0) pg / mL.

[0088] 5. Safety index detection: No obvious abnormality, the drug safety is relatively good. However, compared with the complete formula, there is still room for improvement in some aspects.

[0089] Example 6: Vinegar Corydalis + Stephania tetrandra (combination comparison of two drugs)

[0090] 1. Raw material preparation and preparation of formulations

[0091] 1. Take 360g of vinegar-soaked Corydalis yanhusuo and 290g of Stephania tetrandra and prepare pills.

[0092] 2. Clinical application and effect observation

[0093] 1. Select 100 patients for treatment and observation.

[0094] 2. Symptom improvement: The total effective rate was 60%. The average score of joint swelling was 1.2±0.3 points after treatment, the average score of joint pain was 1.4±0.3 points after treatment, and the average score of flexion and extension difficulty was 1.0±0.2 points after treatment.

[0095] 3. Joint function index detection: The average joint range of motion increased by (11±5)°, the average grip strength (upper limb) increased by (3±1)kg, and the walking ability (lower limb) score increased by (1.8±0.8) points.

[0096] 4. Inflammatory index detection: CRP dropped to (10.5±2.2) mg / L, ESR dropped to (30±8) mm / h,

[0097] IL-1β decreased to (6.0±1.5) pg / mL, and TNF-α decreased to (4.5±1.0) pg / mL.

[0098] 5. Safety index detection: No obvious adverse events were found, but the therapeutic effect was not as ideal as the complete formula1.

[0099] Example 7: Smilax glabra + Stephania tetrandra (combination comparison of two drugs)

[0100] 1. Raw material preparation and preparation of formulations

[0101] 1. Weigh 360g of Rhizoma Smilacis Glabrae and 290g of Radix Stephaniae Tetrandrae and make pills according to the process of Example 1.

[0102] 2. Clinical application and effect observation

[0103] 1. 100 patients were selected as the research subjects.

[0104] 2. Symptom improvement: The total effective rate was 62%. The average score of joint swelling was 1.1±0.3 points after treatment, the average score of joint pain was 1.3±0.3 points after treatment, and the average score of flexion and extension difficulty was 0.9±0.2 points after treatment.

[0105] 3. Joint function index detection: The average joint range of motion increased by (12±6)°, the average grip strength (upper limbs) increased by (4±2)kg, and the walking ability (lower limbs) score increased by (2.0±1.0) points.

[0106] 4. Inflammatory index detection: CRP dropped to (9.8±2.1) mg / L, ESR dropped to (27±7) mm / h, IL

[0107] -1β dropped to (5.8±1.6) pg / mL, and TNF-α dropped to (4.2±1.1) pg / mL. Safety index detection: No serious adverse reactions occurred, and there was a certain therapeutic effect, but compared with the complete formula Example 8: high dose of vinegar Corydalis + low dose of Smilax glabra + low dose of Stephania tetrandra (dose adjustment comparison)

[0108] 1. Raw material preparation and preparation of formulations

[0109] 1. Prepare 450g of vinegar Corydalis, 300g of Smilax glabra, and 250g of Stephania tetrandra, and carry out processing, crushing, pilling and other operations according to the method of Example 1 to make pills with unchanged packaging specifications.

[0110] 2. Clinical application and effect observation

[0111] 1. Select 100 patients for treatment.

[0112] 2. Symptom improvement: The total effective rate was 70%. The average score of joint swelling was 1.0±0.3 points after treatment, the average score of joint pain was 1.2±0.3 points after treatment, and the average score of flexion and extension difficulty was 0.8±0.2 points after treatment.

[0113] 3. Joint function index detection: The average joint range of motion increased by (14±6)°, the average grip strength (upper limb) increased by (4.5±2)kg, and the walking ability (lower limb) score increased by (2.3±1.0) points.

[0114] 4. Inflammatory index detection: CRP dropped to (8.5±2.0) mg / L, ESR dropped to (25±7) mm / h, IL

[0115] -1β dropped to (5.0±1.5) pg / mL, and TNF-α dropped to (3.8±1.0) pg / mL.

[0116] 5. Safety index detection: Some patients experience mild gastrointestinal discomfort, but it does not affect the treatment. The overall therapeutic effect is improved in some aspects compared to the complete formula, but it also brings a certain risk of adverse reactions1.

[0117] Example 9: Low dose of vinegar-corydalis + high dose of smilax glabra + high dose of tetrandra (dose adjustment comparison)

[0118] 1. Raw material preparation and preparation of formulations

[0119] 1. Weigh 300 g of vinegar Corydalis yanhusuo, 420 g of wild smilax glabra, and 320 g of Stephania tetrandra to prepare pills.

[0120] 2. Clinical application and effect observation

[0121] 1. Conduct treatment observation on 100 patients.

[0122] 2. Symptom improvement: The total effective rate was 68%. The average score of joint swelling was 1.1±0.3 points after treatment, the average score of joint pain was 1.3±0.3 points after treatment, and the average score of flexion and extension difficulty was 0.9±0.2 points after treatment.

[0123] 3. Joint function index detection: The average joint range of motion increased by (13±6)°, the average grip strength (upper limb) increased by (4±2)kg, and the walking ability (lower limb) score increased by (2.1±1.0) points.

[0124] 4. Inflammatory index detection: CRP dropped to (9.2±2.2) mg / L, ESR dropped to (26±7) mm / h, IL

[0125] -1β decreased to (5.3±1.6) pg / mL, and TNF-α decreased to (4.0±1.0) pg / mL.

[0126] 5. Safety index detection: The safety is good, but the therapeutic effect is not significantly better than the complete formula, indicating that the dosage ratio of the original formula is reasonable to a certain extent1.

[0127] Example 10: Changing the starch slurry concentration (process adjustment comparison)

[0128] 1. Raw material preparation and preparation of formulations

[0129] 1. According to the prescription, 360 g of vinegar Corydalis, 360 g of Smilax glabra, and 290 g of Stephania tetrandra were accurately weighed, pre-treated, and crushed, and then the mixed powder was taken, and 12% starch slurry solution (preparation method is the same as Example 1) was added as a binder, and the weight ratio of the powder to the starch slurry was 100:90. The subsequent pilling, drying, polishing, pill selection, packaging and other steps were the same as Example 1.

[0130] 2. Clinical application and effect observation

[0131] 1. Select 100 patients and take the adjusted pills orally, 5g each time, 3 times a day, for 4 weeks.

[0132] 2. Symptom improvement: The total effective rate was 75%. The average score of joint swelling was 0.9±0.3 points after treatment, the average score of joint pain was 1.1±0.3 points after treatment, and the average score of flexion and extension difficulty was 0.7±0.2 points after treatment.

[0133] 3. Joint function index detection: The average joint range of motion increased by (15±6)°, the average grip strength (upper limb) increased by (5±2)kg, and the walking ability (lower limb) score increased by (2.4±1.0) points.

[0134] 4. Inflammatory index detection: CRP dropped to (8.0±2.0) mg / L, ESR dropped to (24±7) mm / h, IL

[0135] -1β dropped to (4.8±1.5) pg / mL, and TNF-α dropped to (3.6±1.0) pg / mL.

[0136] 5. Safety index detection: No obvious adverse reactions were found. The process adjustment improved the therapeutic effect to a certain extent, which may be related to the change in starch slurry concentration affecting pill formation, drug dissolution, etc., but further research and optimization are still needed1.

[0137] (I) Drug compatibility

[0138] 1. Significant overall synergy

[0139] 1. Complete formula of Yanling Zhibi Pills in Example 1 (360 g of vinegar Corydalis, 360 g of Smilax glabra, 290 g of Stephania tetrandra)

[0140] It has shown excellent efficacy in the treatment of rheumatic arthritis and gouty arthritis. It acts on the pathological mechanism of the disease through multiple targets to comprehensively improve the patient's joint symptoms, function and inflammation level. For example, the total effective rate after treatment reached 80%, the symptom scores of joint swelling, pain, flexion and extension difficulties were significantly reduced, the joint function was significantly improved, and the level of inflammatory factors was greatly reduced, reflecting the powerful synergistic effect of various drugs.

[0141] 2. Compared with the case where a single prescription is missing in Example 2-4, the advantages of the complete formula are more prominent.

[0142] (Example 2), when vinegar-containing Corydalis yanhusuo (Example 3) or tetrandra fangji (Example 4) is missing, the total effective rate is significantly reduced, the decrease in symptom scores is reduced, the degree of improvement in joint function is weakened, and the level of reduction in inflammatory factors is not as good as the complete formula, which fully proves that each drug is indispensable in the formula and plays an important therapeutic role together.

[0143] 3. The comparison of the two-drug combination in Examples 5-7 shows that the combination of vinegar corydalis + smilax glabra, vinegar corydalis + fangji, smilax glabra + fangji has a certain effect, but it is not as good as the complete formula. This shows that when the three drugs are combined together, they can produce a more comprehensive and powerful therapeutic effect, and synergistically enhance the effects of anti-inflammatory, swelling, analgesic, wind-clearing and dampness-removing, and joint-opening.

[0144] 2. Reasonable drug dosage ratio affects the efficacy

[0145] 1. Example 8 (high dose of vinegar Corydalis + low dose of Rhizoma Smilacis Glabrae + low dose of Radix Stephaniae Tetrandrae) and Example 9 (low dose of vinegar Corydalis + high dose of Rhizoma Smilacis Glabrae + high dose of Radix Stephaniae Tetrandrae) were adjusted by drug dosage, and the results showed that the formula efficacy after changing the dosage had advantages and disadvantages compared with the complete formula. The total effective rate of Example 8 was 70%, and it performed well in terms of some symptom improvement and index reduction, but some patients had adverse reactions of slight gastrointestinal discomfort; the total effective rate of Example 9 was 68%, and the efficacy was not significantly better than the complete formula. This shows that the dosage ratio of the original formula has a certain rationality after long-term clinical practice and research, and can maintain good safety xy while ensuring the efficacy.

[0146] (II) Preparation process

[0147] 1. Optimization of crushing and mixing processes to improve drug quality

[0148] 1. The mixed pulverization process used in Example 1 overcomes the disadvantages of low powder yield, long time and high cost of single pulverization, taking into account the characteristics of more fibrous smilax glabra in the prescription.

[0149] 95% of the particles passed through an 80-mesh sieve and 100-mesh sieve, and the powder extraction rate reached more than 93%. The crushing time was greatly shortened, and there was no adverse effect on the subsequent preparation molding. This process optimization makes the drug particles finer, and the dissolution rate and bioavailability of the active ingredients are improved, thus laying the foundation for the drug to exert good therapeutic effects.

[0150] 2. Key parameters of the formulation molding process affect the quality of pills

[0151] 1. The binder is a 15% starch slurry aqueous solution (Example 1). It has been verified by experiments that it can make the drug powder and the binder combine well, the prepared drug pellets are moderately hard and soft, the pill making is smooth, and the pill shape is uniform and good. When the starch slurry concentration is changed to 12% (Example 10), although the total effective rate is increased to 75%, the therapeutic effect is improved in some aspects, but this also shows that the starch slurry concentration may have an important influence on the quality of the pills and the release of the drug, which further illustrates that the selection of the 15% starch slurry concentration in the original process is determined after research, which is of great significance to ensure the quality and efficacy of the pills.

[0152] 2. During the pill making process, when the equipment cutter and the strip outlet are adjusted to a particle size of 4 mm (Example 1), the pill shape is optimal and the pill making is smooth. The drying temperature is controlled at 80°C for 5 hours (Example 1), which can make the pills moderate in hardness, good in taste and dissolve quickly, which is conducive to the absorption and function of the drug in the body. The precise control of these process parameters ensures the quality of the pills, which in turn affects the therapeutic effect of the drug.

[0153] 2. Comparison of Advantages

[0154] (I) Comparison with other similar Chinese medicine preparations

[0155] 1. Better efficacy

[0156] 1. Compared with some traditional Chinese medicine preparations for the treatment of arthralgia on the market, the complete formula of Yanling Zhibi Pills shows more significant effects in improving joint symptoms, reducing the level of inflammatory factors, and improving joint function. For example, the score reduction of symptoms such as joint swelling and pain after treatment with some traditional Chinese medicine preparations is small, the total effective rate is lower than that of Yanling Zhibi Pills, and the effect on regulating inflammatory factors is not obvious. This is due to the precise drug compatibility and optimized preparation process of Yanling Zhibi Pills, which enables it to play a more effective role in the pathological mechanism of arthralgia.

[0157] 2. Good security

[0158] 1. In terms of safety, through the observation of Examples 1-10, Yanling Zhibi Pills have no obvious effect on the patient's blood routine, liver and kidney function and other indicators under normal dosage and process, and have few adverse reactions. However, some other Chinese medicine preparations may have certain safety risks due to complex drug ingredients, non-standard processing or preparation processes, such as causing gastrointestinal discomfort, liver and kidney function damage, etc. The strict raw material quality control, standardized processing and preparation process, and reasonable drug compatibility of Yanling Zhibi Pills jointly guarantee its good safety.

[0159] (II) Comparison between different embodiments shows advantages

[0160] 1. Complete formula with outstanding advantages

[0161] 1. It can be clearly seen from the comparison between Example 1 and Examples 2-4 that the complete formula has an absolute advantage in therapeutic effect. The lack of any one medicine will greatly reduce the efficacy, whether it is symptom improvement, joint function recovery or inflammation suppression. This shows that the formula of Yanling Zhibi Pills has been carefully designed, and each medicine cooperates with each other, and together they constitute an organic whole, exerting the best therapeutic effect.

[0162] 2. Process adjustments require careful consideration

[0163] 1. Although the curative effect is improved to a certain extent after changing the starch slurry concentration in Example 10, it also indicates that the process adjustment may bring about various effects. While pursuing better curative effect, it is necessary to comprehensively consider factors such as possible adverse reactions and cost changes. The process parameters in Example 1 are determined after many considerations and experiments, and can maintain good pill quality and safety while ensuring the curative effect, which reflects the rationality and stability of the original process.

[0164] In summary, Yanling Zhibi Pills have significant advantages in treating arthralgia through reasonable drug compatibility and scientific preparation technology, and the comparative study between different embodiments provides an important basis for further optimization and understanding of the preparation.

Claims

1. A Chinese medicine preparation for treating arthralgia, characterized in that: The invention is mainly prepared from the following raw materials in parts by weight: 360 parts of vinegar-cured Corydalis yanhusuo, 360 parts of wild smilax glabra and 290 parts of tetrandra tetrandrae.

2. The Chinese medicine preparation according to claim 1, characterized in that: The Rhizoma Smilacis Glabrae is the main drug.

3. The Chinese medicine preparation according to claim 1, characterized in that: The vinegar-corydalis yanhusuo and fangji are adjuvant drugs.

4. A method for preparing the Chinese medicine preparation according to claim 1, characterized in that: The following steps are involved: Raw material pretreatment: Identify and inspect each medicinal material. For vinegar-corydalis, clean corydalis, fry until dry, or cook it in vinegar until the vinegar is absorbed, cut into thick slices or crush it before use. For uncut smilax, soak, wash, moisten, cut into thin slices, and dry. For tetrandra, remove impurities, soak briefly, wash, moisten, cut into thick slices, and dry. Crushing process: Spread the prescription pieces of the preparation flat on a stainless steel plate with a thickness of 1 cm, put them into an oven, dry them at 70°C for 5 hours, and then mix and crush them according to the prescription ratio. 100% of the powder is passed through an 80-mesh sieve and 95% is passed through a 100-mesh sieve to obtain a mixed powder. Preparation molding process: Add 15% dry starch to water to make starch slurry as a binder, take an appropriate amount of dry starch, and use boiling water to make a paste. Add the crushed and weighed powder into a mixer, and add 15% starch slurry aqueous solution at a temperature of 70°C according to the powder-slurry ratio of 100:90, stir for 10 minutes, adjust the equipment tool and the outlet to make pills with a diameter of 4mm, cool the prepared pills in a clean area first, then spread them out on plates, use hot air circulation drying method, dry at 80°C for 5 hours, polish the dried water pills in a water chestnut-type sugar coating machine, add purified water for rotational friction, and use hot and cold air to dry the surface moisture, use manual pill selection to pick out connected pills and residual pills, and then test the appearance, moisture content <9%, and dissolution time <60min of the water pills according to the requirements of the pharmacopoeia; Packaging: The inner packaging uses a medicinal composite film and is sealed using a water pill packaging machine. Each bag contains 5g, and the filling volume difference is controlled within ±6% of 5g. It is accurately coded at the corresponding position. The outer packaging is to put the sealed medicine bags of the inner packaging into the outer packaging box with relevant information according to the specification quantity.

5. The preparation method according to claim 4, characterized in that: In the pulverizing process, the drying temperature is 70°C and the drying time is 5 hours. This condition does not destroy the effective ingredients and makes the weight loss of the medicinal pieces meet the requirements, ensuring that the microbial limits meet the standards and are suitable for pulverization. The powder yield of the mixed pulverized medicinal powder reaches more than 93%, has no adverse effect on subsequent screening, and the pulverizing time is greatly shortened.

6. The preparation method according to claim 4, characterized in that: In the preparation molding process, the starch slurry solution is prepared by taking an appropriate amount of dry starch, making it into a paste with boiling water, adding 15% starch slurry aqueous solution to the medicinal powder at a powder-to-slurry ratio of 100:90, stirring at 70°C for 10 minutes, and the pilling effect is good. When dried, it is dried at 80°C for 5 hours to obtain pills with moderate hardness.