Freeze-dried powder of pharmaceutical composition containing zaocys dhumnade and preparation method of freeze-dried powder

Abstract

The invention relates to the technical field of traditional Chinese medicine freeze-dried powder, in particular to freeze-dried powder of a pharmaceutical composition containing zaocys dhumnade and a preparation method of the freeze-dried powder. The freeze-dried powder is prepared from the following raw materials in parts by weight: 500 to 1500 parts of zaocys dhumnade, 100 to 1000 parts of long-noded pit viper, 100 to 1000 parts of glutinous rice, 10 to 60 parts of distiller's yeast, 50 to 100 parts of herba leonuri, 30 to 80 parts of radix rehmanniae recen, 30 to 80 parts of herba patriniae, 30 to 80 parts of radix pulsatillae, 20 to 60 parts of flos carthami and 50 to 100 parts of radix salviae miltiorrhizae. According to the traditional Chinese medicine composition, prescription compatibility is optimized, the curative effect of the formula is remarkably enhanced, the treatment and refining process of the medicinal raw materials is optimized, and the utilization rate of the medicinal raw materials is greatly increased; meanwhile, the product is presented in the form of freeze-dried powder, so that the activity of the medicinal materials is better ensured.

Description

Technical Field

[0001] The invention relates to the technical field of freeze-dried powder of traditional Chinese medicine, in particular to freeze-dried powder of a medicine composition containing japon and a preparation method thereof. Background Art

[0002] Traditional medicine has long noticed how to crush dried snakes to maximize their medicinal effects. The ancient method used iron grinding boats and copper mortars to impact and grind the dried snakes into powder, and some used tiles and porcelain pieces to dry and grind them into powder. These powder making methods are far from meeting the needs of modern medical care. Clinically, it is necessary to solve the problem of powders with high efficacy, rapid effect, simple preparation, convenient transportation and carrying, and moisture-proof and pollution-proof. Therefore, oral capsules have been developed in recent years.

[0003] However, there are still many defects in the actual production process. The first is the processing of raw materials. The existing mature technology often uses dried black-banded snakes, so coal baking or charcoal baking will inevitably be used in the drying process, which cannot avoid the generation of impurities; slightly more advanced technology uses electric drying ovens, but the drying process often causes certain damage and impact on the original nutrients and effective ingredients of the snake body, thereby affecting the effect of the snake powder.

[0004] Studies have found that black snake meat mainly contains protein and fat. When used as a medicinal material, in addition to the active medicinal ingredients contained in it, the protein and fat have little effect on the medicine itself. Therefore, when used as a medicine, the dried product is often used, and then different methods are used to extract it. Only the extract is used, so the residue is directly discarded, reducing the utilization rate of the raw materials of the medicine.

[0005] Among the common combinations of black-necked snakes, the formula for treating rheumatoid arthritis is black-necked snakes, processed Chuanwu and raw Rehmannia root. The formula is changed according to symptoms to black-necked snakes, cinnamon twigs, angelica, red peony root, peach kernel and safflower to treat rheumatoid arthritis by using the method of resolving phlegm, activating blood circulation and unblocking collaterals. In the pharmaceutical process, the method of wine-roasting is often used to treat black-necked snakes. On this basis, our researchers have tried to improve the wine-roasting method and developed a pharmaceutical method with a higher utilization rate for black-necked snakes and their compatible medicinal materials, and tried to make the final form of the medicine into freeze-dried powder, which better ensures the activity of the medicinal materials and also increases the utilization rate of the medicinal materials. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide a freeze-dried powder of a pharmaceutical composition containing garter snake and a preparation method thereof, optimize the compatibility of the prescription, significantly enhance the efficacy of the formula, and optimize the processing and refining process of the medicinal raw materials, greatly improving the utilization rate of the medicinal raw materials; at the same time, the product is presented in the form of freeze-dried powder, which better ensures the activity of the medicinal materials.

[0007] In order to solve the above technical problems, the present invention adopts the following technical solutions: A freeze-dried powder of a pharmaceutical composition containing garter snakes, the freeze-dried powder comprising the following raw materials in parts by weight: 500-1500 parts of garter snakes, 100-1000 parts of white-flowered snakes, 100-1000 parts of glutinous rice, 10-60 parts of distiller's yeast, 50-100 parts of motherwort, 30-80 parts of raw rehmannia root, 30-80 parts of patrinia herba, 30-80 parts of pulsatilla, 20-60 parts of safflower and 50-100 parts of salvia miltiorrhiza.

[0008] Preferably, the distiller's yeast is a mixture of red yeast rice and white yeast rice, both traditional Chinese medicines, in a weight ratio of 5:1.

[0009] The method for preparing a freeze-dried powder of a pharmaceutical composition containing garter snake described in any one of the above comprises the following steps: S1, removing the heads and internal organs of the cultivated black-banded snake and white-flowered snake, washing them with distilled water, steaming glutinous rice for 20 minutes and then cooling to 30° C.; mixing glutinous rice with the black-banded snake and white-flowered snake meat, and then adding sugar, distiller's yeast and mountain spring water for fermentation, and filtering to separate the fermentation liquid and solid matter for later use; S2, adding the compatible medicinal materials to the fermentation liquid separated in step S1 according to the proportion, sealing and soaking in a constant temperature and light-proof environment for 7 to 15 days, filtering and taking the soaking liquid for later use; S3, distilling and purifying the soaking liquid in step S2 to obtain a condensed distillate for standby use; S4, vacuum drying the solid matter separated in step S1 and then crushing it to obtain a powder for later use; S5, adding the powder product in step S4 to the distillate obtained in step S3 to dissolve and mix evenly, freezing the mixed solution, vacuum dehydrating and drying, and then crushing it into powder for a second time to obtain freeze-dried snake powder.

[0010] Preferably, the fermentation temperature of step S1 is 30-38° C., and the fermentation time is 7-12 days.

[0011] Preferably, in step S3, a distillation device is placed and heated to 78° C. for extraction.

[0012] Preferably, the solid material processing conditions in step S4 are: freezing condition -20~-25°C, vacuum condition 8Pa~13Pa.

[0013] Preferably, the specific method for preparing the freeze-dried powder of Garcinia charantia in step S5 comprises the following steps: S51, pre-freezing: cooling the mixed solution to -40~-45°C and maintaining it for 2~3 hours to completely freeze the mixed solution; S52, sublimation drying: turn on the vacuum pump, control the vacuum degree to 3.8Pa~7.6Pa, uniformly heat to -15~-20℃, keep warm for 1~2h, uniformly heat to -10~-8℃ again, keep warm for 5~7h; S53, secondary drying: continue to heat up to 21~25℃, vacuum condition 0.8Pa~1.3Pa, maintain for 3~4h; S54, crushing, crushing the product dried in step S53, and packaging after sterilization to obtain the freeze-dried powder of the black-necked snake.

[0014] The principles and advantages of this solution are as follows: The recipe selects black-striped snake, salvia miltiorrhiza and safflower as the main ingredients. They are sweet and mild in nature and belong to the liver meridian. Black-striped snake is an insect medicine. With its fleshy and bloody texture and its nature of jumping and attacking, it can penetrate the marrow and collaterals, search and remove the evil in the collaterals to penetrate the root of the disease, attack and expel the evil accumulation, and relieve limb movement disorders. Salvia miltiorrhiza can promote blood circulation and remove blood stasis, relieve pain, clear the heart and relieve vexation, cool blood and eliminate carbuncle, and can regulate the qi of the whole body. Safflower is pungent and warm, non-toxic, and enters the heart and liver meridians. It has the effects of promoting blood circulation, dredge menstruation, and relieve pain. The three ingredients work together to transform yang with pungent and sweet flavors, harmonize the Ying and Wei, and promote slight sweating of the body to achieve the effect of removing rheumatism; at the same time, it can promote blood circulation, dredge blood stasis, and eradicate joint pain.

[0015] White flower snake, motherwort and raw rehmannia are the ministers. White flower snake is sweet, salty and warm in nature. It goes to the internal organs and builds the skin. It penetrates the bones to search for wind, calms convulsions and treats all kinds of wind. Motherwort can promote blood circulation and regulate menstruation, promote diuresis and reduce swelling, and maintain kidney function to prevent the main medicine from being too strong and causing kidney metabolic burden. According to Western medicine theory: rheumatoid arthritis is low immunity, so according to Western medicine ingredients, motherwort contains a variety of trace elements: selenium has the effect of enhancing the vitality of immune cells, alleviating the occurrence of atherosclerosis and improving the body's defense system against diseases; manganese can resist oxidation, prevent aging, resist fatigue and inhibit the proliferation of cancer cells, and strengthen immunity. Raw rehmannia is sweet and bitter in taste and cold in nature. It has the effects of clearing heat and cooling blood, nourishing yin and promoting body fluid, and is used to balance the strong nature of insect medicine to achieve yin and yang harmony. The three medicines are matched to replenish the blood of the nutrient and defensive qi and blood, and help the main medicine to work. Assisted by Patrinia and Pulsatilla, Patrinia can clear away heat and detoxify, eliminate carbuncle and discharge pus, remove blood stasis and relieve pain, and is used for sedation and anti-inflammatory, antibacterial and immune enhancement. Pulsatilla cools blood and stops dysentery, clears the liver and improves eyesight, and harmonizes the liver and gallbladder fire caused by insect medicine and warm herbs. The whole formula is mainly based on the insect medicine black-spotted snake to dredge the meridians, relieve limb movement disorders caused by rheumatism, and after being supplemented by other herbs, it is good at removing dampness, removing blood stasis and relieving pain, harmonizing qi and blood, protecting the liver and nourishing the spirit, so that all evils are removed and the righteous qi is not damaged.

[0016] Beneficial effects of the present invention: The formula of the present invention is used to treat rheumatoid diseases. Compared with the existing formula, it is optimized and improved, some medicinal materials are removed, and motherwort and salvia miltiorrhiza are introduced, which greatly improves the therapeutic effect of the formula. This side uses dwarf snake, salvia miltiorrhiza and safflower as the main medicine, mainly for rheumatoid arthritis to play the role of promoting blood circulation and removing blood stasis, relieving pain and cooling blood, and improving blood circulation. On this basis, it is supplemented with white flower snake, motherwort and raw rehmannia to strengthen the drug effect, dredge the meridians, and improve immunity; it is supplemented with patrinia and pulsatilla to play the role of anti-inflammatory and sedative, and strengthen the improvement and treatment of joint inflammation. The whole side cooperates with each other, greatly improving the therapeutic effect of rheumatoid arthritis and other related diseases.

[0017] The invention prepares the formulated medicinal materials into freeze-dried powder, and the conventional high-temperature treatment is avoided in the preparation process, so the activity of the effective ingredients of the medicinal materials can be better retained, and the efficacy and utilization rate of the medicinal materials can be improved.

[0018] The preparation process of the present invention is different from the traditional wine-fried drying processing mode in the processing of japon and white-flowered snake, and directly ferments fresh snake meat with glutinous rice, and then distills and purifies, and the liquid product and solid product obtained by separation are processed and applied respectively, and the utilization rate of medicinal materials is increased to the highest. In the process of japon and white-flowered snake fermenting with glutinous rice, their own protein and fat are rapidly acidified by microorganisms, inhibiting the growth and reproduction of spoilage bacteria and pathogenic bacteria, and the coagulation of muscle protein is well retained when the effective ingredients are separated, and the fermentation process also produces acetic acid, propionic acid, ethanol, hydrogen peroxide, antimicrobial peptides and bacteriocin and other substances, and develops other effects of medicinal materials. The fermented liquid finally obtained contains alcohol after distillation and purification, and after subsequent freeze-drying process treatment, contains 2-8% ethanol in the final freeze-dried powder, so that the freeze-dried powder can be dissolved more thoroughly when used, and the content will not bring side effects to the patient itself. DETAILED DESCRIPTION

[0019] In order to facilitate the understanding of those skilled in the art, the present invention is further described below in conjunction with examples and appended tables. The contents mentioned in the implementation modes are not intended to limit the present invention.

[0020] Black-necked snake: Also called black snake, it is mostly blue-gray or dark brown. After the internal organs are removed from the dried body, it can be used as a Chinese medicinal material. It is sweet and mild in nature, belongs to the liver meridian, and has high medicinal value. 1. Dispel wind and relieve pain: After being used as medicine, black-necked snake can relieve stubborn joint and muscle pain caused by wind and cold. 2. Unblock the meridians: Black-necked snake has the effect of unblocking meridians and relieving limb movement disorders. It can treat numbness, stroke, facial paralysis, and also has an auxiliary therapeutic effect on skin diseases such as scabies and ringworms.

[0021] White Flower Snake: Its functions and indications are to dispel rheumatism, penetrate tendons and bones, and calm convulsions. It can treat rheumatic paralysis, joint pain, leprosy, scabies, convulsions in children, tetanus, bayberry sores, scrofula and malignant ulcers.

[0022] Motherwort: Promotes blood circulation and regulates menstruation, promotes diuresis and reduces swelling. Used for irregular menstruation, dysmenorrhea, amenorrhea, lochia retention, edema and oliguria; acute nephritis edema. Contains a variety of trace elements. Selenium can enhance the vitality of immune cells, alleviate the occurrence of atherosclerosis, and improve the body's defense system against diseases; manganese can resist oxidation, prevent aging, resist fatigue, and inhibit the proliferation of cancer cells.

[0023] Raw Rehmannia: It tastes sweet and bitter, and is cold in nature. It has the effects of clearing away heat and cooling blood, nourishing yin and promoting body fluid. It can be used to treat symptoms such as febrile disease damaging yin, high fever and thirst, coma, vomiting blood, epistaxis, constipation, etc.

[0024] Patrinia scabra: It has multiple pharmacological effects such as antibacterial, immune-enhancing, anti-tumor, and sedative. It can clear away heat and toxic substances, eliminate carbuncle and discharge pus, remove blood stasis and relieve pain. It is commonly used for intestinal carbuncle, lung carbuncle, dysentery, abdominal pain caused by blood stasis after childbirth, carbuncle, furuncle, etc.

[0025] 1. Pulsatilla: Pulsatilla has the effect of cooling blood and stopping dysentery. It is used to treat damp-heat dysentery and heat-toxic blood dysentery. It is used to treat heat-toxic dysentery and is often used together with Coptis chinensis and Fraxinus chinensis, which can clear away heat, dry dampness and stop dysentery. 2. Pulsatilla can also clear away heat and detoxify. It is used to treat heat-toxic syndromes such as sores, carbuncles, swelling and toxicity, and hemorrhoids. It can be taken orally or applied locally. It is often used together with Taraxacum mongolicum and Forsythia suspensa. 3. Pulsatilla has the effect of clearing the liver and improving eyesight. It is used to treat red and swollen eyes, bitter mouth, irritability, and constipation caused by excessive liver and gallbladder fire, which disturbs the meridians, resulting in blockage of meridians, blood stagnation and qi stagnation.

[0026] Safflower: pungent and warm, non-toxic, enters the heart and liver meridians, and has the effects of promoting blood circulation and menstruation, removing blood stasis and relieving pain. 1. Promoting blood circulation and dredging collaterals: Safflower is a relatively common Chinese herbal medicine, which can mainly promote blood circulation and menstruation, and can be used to treat amenorrhea or dystocia. It can also improve postpartum lochia or uterine fibroids, and can also play a good role in regulating ovarian cysts. 2. Removing blood stasis and relieving pain: Safflower can remove blood stasis and relieve pain. It can mainly be used to treat symptoms such as headaches or chest pains. It can also play a good role in regulating joint pain or pain caused by injuries.

[0027] Salvia miltiorrhiza: promotes blood circulation and removes blood stasis, relieves menstruation and relieves pain, clears the heart and eliminates restlessness, cools blood and eliminates carbuncles. It has multiple pharmacological effects such as anti-coagulation, anti-thrombosis, improves microcirculation, improves blood rheology, resists myocardial ischemia, resists cerebral ischemia, antioxidant, anti-tumor, anti-inflammatory, anti-fibrosis, and cholesterol-lowering.

[0028] Example 1

[0029] S1, remove the heads and internal organs of cultured black-banded snakes and white-flowered snakes, wash them with distilled water, steam glutinous rice for 20 minutes and cool to 30°C; mix 100g glutinous rice, 500g black-banded snakes and 1000g white-flowered snake meat, sprinkle with 24g sugar, 8.33g red yeast, 1.67g white yeast and 3000g spring water for fermentation, the fermentation temperature is 30-38°C, the fermentation time is 10d, and filter press to separate the fermentation liquid and solid matter for later use; S2, weigh 50g of Leonurus japonicus, 30g of Radix Rehmanniae, 30g of Patrinia chinensis, 30g of Pulsatilla chinensis, 20g of Carthamus tinctorius and 50g of Salvia miltiorrhiza, add the above-mentioned compatible medicinal materials to the fermentation liquid separated in step S1, seal and soak in a constant temperature and light-proof environment for 15 days, filter and take the soaking liquid for later use; S3, placing the soaking liquid in step S2 into a distillation device, heating it to 78° C. for distillation and purification, and obtaining a condensed distillate for later use; S4, putting the solid substance separated in step S1 into a vacuum freeze dryer, setting the freezing condition to -23°C and the vacuum condition to 10Pa, and crushing it after vacuum drying to obtain a preliminary powder for use; S5, adding the powder product in step S4 to the distillate obtained in step S3 to dissolve and mix evenly, freezing the mixed solution, vacuum dehydrating and drying, and then crushing it into powder for a second time to obtain freeze-dried snake powder. The specific operation is: S51, pre-freezing: cooling the mixed solution to -40~-45°C and maintaining it for 3 hours to completely freeze the mixed solution; S52, sublimation drying: turn on the vacuum pump, control the vacuum degree to 5.2Pa, uniformly heat to -20℃, keep warm for 2h, uniformly heat to -8℃ again, keep warm for 7h; S53, secondary drying: continue to heat to 21 °C, vacuum condition 0.8 Pa, maintain for 3.5 h; S54, crushing, crushing the product dried in step S53, and packaging after sterilization to obtain freeze-dried powder 1.

[0030] Example 2

[0031] S1, remove the heads and internal organs of cultivated black-banded snakes and white-flowered snakes, wash them with distilled water, steam glutinous rice for 20 minutes and cool to 30°C; mix 100g glutinous rice, 1000g black-banded snakes and 500g white-flowered snake meat, sprinkle with 30g sugar, 15g red yeast, 3g white yeast and 3000g spring water for fermentation, the fermentation temperature is 30-38°C, the fermentation time is 10d, and filter press to separate the fermentation liquid and solid matter for later use; S2, weigh 80g of Leonurus japonicus, 50g of Radix Rehmanniae, 50g of Herba Patriniae, 50g of Herba Pulsatillae, 40g of Carthamus tinctorius and 80g of Salvia miltiorrhizae, add the above-mentioned compatible medicinal materials to the fermentation liquid separated in step S1, seal and soak in a constant temperature and light-proof environment for 15 days, filter and take the soaking liquid for later use; S3, placing the soaking liquid in step S2 into a distillation device, heating it to 78° C. for distillation and purification, and obtaining a condensed distillate for later use; S4, putting the solid substance separated in step S1 into a vacuum freeze dryer, setting the freezing condition to -23°C and the vacuum condition to 10Pa, and crushing it after vacuum drying to obtain a preliminary powder for use; S5, adding the powder product in step S4 to the distillate obtained in step S3 to dissolve and mix evenly, freezing the mixed solution, vacuum dehydrating and drying, and then crushing it into powder for a second time to obtain freeze-dried snake powder. The specific operation is: S51, pre-freezing: cooling the mixed solution to -40~-45°C and maintaining it for 3 hours to completely freeze the mixed solution; S52, sublimation drying: turn on the vacuum pump, control the vacuum degree to 5.2Pa, uniformly heat to -20℃, keep warm for 2h, uniformly heat to -8℃ again, keep warm for 7h; S53, secondary drying: continue to heat to 21 °C, vacuum condition 0.8 Pa, maintain for 3.5 h; S54, crushing, crushing the product dried in step S53, and packaging after sterilization to obtain freeze-dried powder 2.

[0032] Example 3

[0033] S1, remove the heads and internal organs of cultivated black-banded snakes and white-flowered snakes, wash them with distilled water, steam glutinous rice for 20 minutes and cool to 30°C; mix 1000g glutinous rice, 1500g black-banded snakes and 100g white-flowered snake meat, sprinkle with 40g sugar, 50g red yeast, 10g white yeast and 3000g spring water for fermentation, the fermentation temperature is 30-38°C, the fermentation time is 10d, and filter press to separate the fermentation liquid and solid matter for later use; S2, weighing 100g of Leonurus japonicus, 80g of Radix Rehmanniae, 80g of Herba Patriniae, 80g of Pulsatillae Scutellariae, 60g of Carthamus tinctorius and 100g of Salvia miltiorrhiza, adding the above-mentioned compatible medicinal materials to the fermentation liquid separated in step S1, sealing and soaking in a constant temperature and light-proof environment for 15 days, filtering and taking the soaking liquid for later use; S3, placing the soaking liquid in step S2 into a distillation device, heating it to 78° C. for distillation and purification, and obtaining a condensed distillate for later use; S4, putting the solid substance separated in step S1 into a vacuum freeze dryer, setting the freezing condition to -23°C and the vacuum condition to 10Pa, and crushing it after vacuum drying to obtain a preliminary powder for use; S5, adding the powder product in step S4 to the distillate obtained in step S3 to dissolve and mix evenly, freezing the mixed solution, vacuum dehydrating and drying, and then crushing it into powder for a second time to obtain freeze-dried snake powder. The specific operation is: S51, pre-freezing: cooling the mixed solution to -40~-45°C and maintaining it for 3 hours to completely freeze the mixed solution; S52, sublimation drying: turn on the vacuum pump, control the vacuum degree to 5.2Pa, uniformly heat to -20℃, keep warm for 2h, uniformly heat to -8℃ again, keep warm for 7h; S53, secondary drying: continue to heat to 21 °C, vacuum condition 0.8 Pa, maintain for 3.5 h; S54, crushing, crushing the product dried in step S53, and packaging after sterilization to obtain freeze-dried powder 3.

[0034] Comparative Example 1 According to the formulation of Example 2, freeze-dried powder was prepared without using a fermentation process: The heads and internal organs of the cultured black-banded snake and white-flowered snake were removed, washed with distilled water, and the snake meat was roasted with wine and dried according to the processing method of the Pharmacopoeia. 80g of Leonurus japonicus, 50g of Radix Rehmanniae, 50g of Patriniae Herba, 50g of Pulsatillae Scutellariae, 40g of Carthamus tinctorius, and 80g of Salvia miltiorrhiza were weighed, and the above-mentioned compatible medicinal materials were mixed and boiled, and the filtrate was taken for later use.

[0035] The filtrate is subjected to reduced pressure distillation, and the obtained distillate is used to prepare the lyophilized powder of the black-necked snake. The specific operation is as follows: pre-freezing: cooling the mixed solution to -40~-45℃, keeping it for 3h to completely freeze the mixed solution; sublimation drying: turning on the vacuum pump, controlling the vacuum degree to 5.2Pa, uniformly heating to -20℃, keeping it warm for 2h, and uniformly heating to -8℃ again, keeping it warm for 7h; secondary drying: continuing to heat to 21℃, vacuum condition 0.8Pa, keeping it for 3.5h; crushing, crushing the product dried in step S53, sterilizing and packaging to obtain lyophilized powder 4.

[0036] Comparative Example 2 Black snake wine The method is to use the existing public formula to brew: take a dried black-necked snake, remove the head, tail and internal organs, put it in a clean wine bottle, add 500 ml of white wine, and seal it and soak it for 3 to 5 days. Take 10 to 20 ml three times a day. Efficacy: dispel wind and dredge meridians, attack toxins and relieve pain. It can be used for rheumatic arthralgia, bone and joint tuberculosis, skin numbness, poliomyelitis, leprosy, rash, scabies, etc.

[0037] Comparative Example 3 Ginseng Snake Dip Use the existing public formula to brew: 50 grams of Salvia miltiorrhiza, 10-25 grams of white flower snake. Chop the above medicines, put them into the wine jar, add 1250 ml of 60-proof liquor, seal and soak for 7 days. Take 10-20 ml once a day before going to bed at night. Efficacy: dispel wind and activate collaterals, promote blood circulation and remove blood stasis. It is suitable for symptoms such as soreness and heaviness of limbs, pain in joints and tendons, and wandering caused by rheumatic paralysis of muscles and meridians.

[0038] Test Example 1 This test design adopts a simple random, controlled, non-blind research method. SPSS15.0 statistical software was used to obtain random numbers, and the selected subjects were randomly assigned to the control group and the experimental group using a simple random method.

[0039] The experimental plan is as follows: Principles of case selection (1) Diagnostic criteria: (1.1) Western medical diagnostic criteria The diagnostic criteria for RA jointly issued by ACR / EULAR in 2009 are adopted: ① Cumulative number of joints (0-5 points): 1 medium-sized or large joint (0 point); 2-10 medium-sized or large joints (1 point); 1-3 small joints (2 points); 4-10 small joints (3 points); >10 small joints (5 points).

[0040] ② Serological antibody test (0-3 points): Both RF and anti-CCP are negative (0 points); at least one of RF or anti-CCP is positive at a low titer (2 points); at least one of RF or anti-CCP is positive at a high titer (3 points).

[0041] ③ Duration of synovitis (0-1 point): <6 weeks (0 point); >6 weeks (1 point).

[0042] ④ Acute phase reactants (0-1 point): both CRP and ESR are normal (0 point); CRP or ESR is elevated (1 point).

[0043] Note: In each part, select the highest score. If a patient has 5 small joints and 4 large joints affected, he / she will get 3 points. If the sum of the scores obtained in the four parts is ≥ 6 points, RA is diagnosed. Number of affected joints: excluding the distal interphalangeal joints, the first carpometacarpal joints and the first metatarsal joints; medium and large joints: both shoulders, elbows, hips, knees and joints; small joints: except for the medium and large joints, and excluding the distal interphalangeal joints, the first carpometacarpal joints and the first metatarsal joints. Low titer is defined as exceeding the upper limit of normal, but not higher than 3 times the upper limit of normal. High titer is defined as exceeding 3 times the upper limit of normal.

[0044] (1.2) TCM diagnostic criteria The TCM diagnostic criteria for RA are formulated with reference to the diagnostic criteria for rheumatoid arthritis in the "Traditional Chinese Medicine Industry Standards of the People's Republic of China·TCM Disease Diagnosis and Efficacy Standards", as follows: Initially, the disease presents with symmetrical pain and swelling in small joints, usually in the finger joints or back, poor mobility, and morning stiffness. The disease starts slowly, persists for a long time and does not heal, and the body gradually becomes thinner. It is often caused by repeated attacks of wind, cold and dampness. The affected joints become fusiform and swollen after a long period of illness, painful when moving, and resistant to pressure. In the later stage, the joints become deformed and stiff, with a smooth surface, and the surrounding muscles atrophy. In a few cases, subcutaneous nodules may be seen; Rheumatoid factor is positive, and the erythrocyte sedimentation rate may increase during the attack period. X-rays may show osteoporotic changes, or joint bone surface invasion, subluxation or dislocation, bone ankylosis, and joint surface fusion.

[0045] (1.3) TCM syndrome diagnostic criteria According to the "Common Symptoms of Rheumatism" and "Differentiation and Treatment of Rheumatoid Arthritis" in the 2nd edition of "Practical Chinese Medicine Rheumatology", it is divided into the following 8 types: ① Rheumatic arthralgia syndrome: symptoms include pain, heaviness, or swelling in the joints of the limbs, wandering pain, difficulty in flexion and extension of the joints, pale red tongue, greasy white tongue coating, and a moist or slippery pulse.

[0046] ② Cold-dampness arthralgia syndrome: symptoms include cold and painful joints of the limbs, local swelling, joint stiffness, difficulty in flexion and extension, local fear of cold, severe pain when cold and less pain when hot, no red skin, fat tongue, pale and dark tongue, greasy or slippery white tongue coating, and stringy or deep and tight pulse.

[0047] ③Damp-heat arthralgia syndrome: symptoms include local swelling and pain in the joints, heaviness, burning sensation or heat when touched, thirst without desire to drink, restlessness, or fever, red tongue with yellow and greasy coating, and moist or slippery pulse.

[0048] ④ Phlegm, blood stasis and numbness syndrome: painful and swollen joints, morning stiffness, difficulty in flexion and extension, nodules around the joints or under the skin, dark purple tongue, thick white or greasy tongue coating, deep, fine and astringent or deep and slippery pulse.

[0049] ⑤Syndrome of deficiency of both Qi and Yin: swollen joints, dry mouth and eyes, dry lips, fatigue and weakness, or emaciation of muscles, red tongue with little fluid and cracks, or enlarged tongue with tooth marks, thin white fur, and deep and weak pulse or deep and fine pulse.

[0050] ⑥ Liver and kidney deficiency syndrome: joint and muscle pain, difficulty in flexion and extension, swollen or deformed and stiff joints, soreness and weakness in the waist and knees, cold joints or local fever, red tongue, thin white fur, and weak pulse.

[0051] ⑦ Syndrome of blood stasis and collateral obstruction: joint pain, or pain worse at night, or stabbing pain, dry and dull skin or even cracked nails, dark tongue with ecchymosis on the edges and tip of the tongue, thin white fur, and thready and wiry pulse.

[0052] ⑧Syndrome of deficiency of both Qi and blood: soreness and weakness in joints and muscles, aggravated after activities, shortness of breath, fatigue, palpitations, or dizziness, pale complexion, or muscle atrophy, or joint deformity, pale tongue, thin white fur, and thready and weak pulse.

[0053] (1.4) Criteria for determining active rheumatoid arthritis Using the evaluation criteria established by ACR, DAS28>5.1 represents severe disease activity, 3.2<DAS28<5.1 represents moderate disease activity, 2.6<DAS28<3.2 represents basic remission, and DAS28<2.6 represents remission.

[0054] (2) Case inclusion criteria, exclusion criteria, suspension or withdrawal criteria, elimination and dropout criteria (2.1) Case inclusion criteria: Meet the diagnostic criteria for RA; be over 18 years old, regardless of gender; have complete clinical data, including general condition, syndrome differentiation, treatment methods and prescription medications; and take Chinese herbal decoctions for treatment.

[0055] (2.2) Exclusion criteria: Female patients under 18 years of age, pregnant or lactating; patients with severe primary diseases such as cardiovascular, cerebrovascular, liver, kidney and hematopoietic system, and mental illness; patients with severe gastric or duodenal ulcer or erosion; patients with severe joint deformity and loss of function; patients with other rheumatic diseases; patients with a history of joint trauma; and patients who are intolerant to this drug.

[0056] 2. Patient selection (1) Doctor-patient communication.

[0057] (2) Medical history collection: Collect and record the patient's demographic information, basic information, medical history, comorbidities / diseases, and allergy history.

[0058] (3) Baseline screening: The baseline screening period refers to the screening before inclusion, which requires the completion of the following items: signing of the informed consent form; collection of demographic data and medical history (including the dosage of immunosuppressants used and the duration of treatment); vital signs (body temperature, respiration, pulse and blood pressure); clinical symptoms and signs; routine blood and urine tests, and occult blood in stool; blood biochemistry (including liver function and kidney function); chest X-ray; disease activity score (DAS28 score); autoantibody detection: rheumatoid factor, etc.

[0059] (4) Patient enrollment: Patients were selected based on whether they signed the informed consent form and the inclusion and exclusion criteria. The patients were divided into two groups, the control group and the treatment group. The treatment course for each group was 1 month, and the efficacy and safety were evaluated after the treatment.

[0060] (5) Grouping and treatment plan (5.1) Control group Control group 1 ① 3 tablets of methotrexate (2.5 mg / tablet), taken orally once a week; ② 1 tablet of leflunomide (10 mg / tablet), orally once a day; ③ Take 1 tablet of loxoprofen sodium (60 mg / tablet) orally 3 times a day (if the joint tenderness or swelling score is ≥ 6 points, add loxoprofen sodium).

[0061] Control group 2 Comparative Example 1: 1 g of freeze-dried powder 4 was dissolved in warm water at about 40° C. and taken orally 3 times a day.

[0062] Control group 3 Comparative Example 2: Black-necked snake wine, 3 times a day, 10 to 20 ml each time.

[0063] Control group 4 Comparative Example 3: Sprinkle with ginseng snake extract, once a day, drink 10-20 ml before going to bed at night.

[0064] (5.2) Experimental group Experimental Group 1 Example 1, freeze-dried powder 1, take 1g of freeze-dried powder and dissolve it in warm water at about 40°C, and take it orally, 3 times a day.

[0065] Experimental Group 2 Example 2, lyophilized powder 2, 1 g of lyophilized powder was dissolved in warm water at about 40° C. and taken orally 3 times a day.

[0066] Experimental Group 3 Example 3, lyophilized powder 3, take 1g of lyophilized powder and dissolve it in warm water at about 40°C, and take it orally, 3 times a day.

[0067] The treatment course was 1 month, and the efficacy and safety were evaluated after 1 month.

[0068] 3. Observation indicators (1) General items: name, gender, age, medical history, medication, etc.

[0069] (2) Clinical observation indicators (2.1) Main symptoms: number of joint tenderness and number of joint swelling.

[0070] (2.2) Score using the visual analogue scale (VAS) (0-100 mm).

[0071] Evaluate the patient's pain: VAS is widely used in clinical pain assessment in my country. The basic method is to use a 10cm long floating ruler with 10 scales on one side, with "0" and "10" on the two ends. "0" means no pain, and "10" means the most severe pain that is unbearable. When used clinically, the scaled side is turned away from the patient, and the patient is asked to mark the corresponding position on the ruler that can represent the degree of pain. The physician will score the patient according to the position marked by the patient. The clinical assessment is "0-2" for "excellent", "3-5" for "good", "6-8" for "acceptable", and > "8" for "poor". The same method before and after clinical treatment can make a relatively objective score and make a relatively objective evaluation of the effect of pain treatment. This method is simple, easy to use, relatively objective, and sensitive. The ruler commonly used in clinical practice currently has a floating mark between the "0" and "10" ends, and scales on the back, which is practical and convenient.

[0072] (2.2) Using the Health Assessment Questionnaire (HAQ) The HAQ disability index is calculated by evaluating whether one can perform the following activities in the past two months: (1) dress oneself (including tying shoelaces and buttons); (2) get in and out of bed by oneself; (3) bring water to one's mouth by oneself; (4) walk on flat ground; (5) wash oneself and dry oneself; (6) turn on and off faucets or bottle stoppers; (7) comb hair; (8) cut vegetables; (9) squat and pick up clothes on the ground; (10) get in and out of cars and other means of transportation; (11) stand up from a chair without using hands to support oneself; (12) go shopping, etc. Each item is scored as follows: 0 = no difficulty; 1 = a little difficulty, can be completed; 2 = relatively difficult, barely able to maintain; 3 = cannot be completed. The sum of the scores for each item is the total score.

[0073] The HAQ discomfort index is calculated by whether you have felt the following in the past 2 months: (1) Do you like your job? (2) Nervous or anxious? (3) Restless, difficult to calm down? Sad or depressed? Difficult to get excited? Each item is scored as follows: 0 = never; 1 = sometimes; 2 = often; 3 = always.

[0074] In this study, the total score was the sum of the disability index and discomfort index.

[0075] (2.3) Inflammatory activity indicators Rheumatoid factor: chemisorption-linked adsorption method, normal value: ≤20IU / ml; The values ​​of each group of patients before treatment and at the first month were recorded and compared.

[0076] IV. Clinical efficacy evaluation (1) DAS28 efficacy evaluation (1.1)DAS28 score The patients' bilateral proximal interphalangeal joints, metacarpophalangeal joints, wrist joints, elbow joints, shoulder joints and knee joints (28 joints) were examined to obtain the swollen joint count (SJC), tender joint count (TJC), and calculate DAS28.

[0077] DAS28: includes total number of joint tenderness, total number of joint swelling, erythrocyte sedimentation rate, and patient's evaluation of overall health status DAS28=0.56×√TJC+0.28×√SJC+0.7×lnESR+0.14×GH Among them, TJC: tender joint count; SJC: swollen joint count; ESR: erythrocyte sedimentation rate (unit: mm / h); GH: General Health Status presented by the visual analog scale (VAS, 0-100 mm).

[0078] (1.2) Efficacy evaluation of DAS28 Significantly effective: After treatment, the patient's DAS28 decreased by ≥1.2; Effective: DAS28 decreased to 0.6-1.2; Ineffective: DAS28 decreased <0.6 or DAS28 was greater than 5.1.

[0079] (2) ACR efficacy evaluation ACR20 criteria: The number of swollen and tender joints decreased by ≥20%; and 3 of the following 5 indicators improved by ≥20%: ① Subject's pain score; ② Subject's overall disease status score; ③ Investigator's overall disease status VAS score; ④ Health Status Questionnaire (HAQ) ⑤ ESR or CRP.

[0080] ACR50 criteria: The number of swollen and tender joints decreases by ≥50% and 3 of the following 5 indicators improve by ≥50% (the 5 indicators are the same as above).

[0081] ACR70 criteria: The number of swollen and tender joints decreases by ≥70% and 3 of the following 5 indicators improve by ≥70% (the 5 indicators are the same as above).

[0082] 5. Evaluation of the efficacy of TCM The nimodipine method was used to calculate the TCM syndrome score and evaluate the efficacy of TCM syndrome. The standards were as follows, referring to the Guiding Principles for Clinical Research of New Chinese Medicines (2002 edition): Clinical cure: clinical symptoms and signs disappear or basically disappear, and the syndrome score decreases by ≥95%.

[0083] Markedly effective: Clinical symptoms and signs were significantly improved, and the syndrome score was reduced by ≥70%.

[0084] Effective: Clinical symptoms and signs improved, and syndrome scores decreased by ≥30%.

[0085] Ineffective: Clinical symptoms and signs have no significant improvement, or even worsen, and the syndrome score decreases by less than 30%. Peripheral serum TNF-α, IL-6, and IL-10 levels were detected by enzyme-linked adsorption assay according to the kit instructions. The values ​​of the levels of each group of patients at baseline and 1 month were recorded and compared.

[0086] 7. Statistical Analysis SPSS 17.0 software was used for data analysis, and the measurement data were expressed as mean ± standard deviation. 2 The measurement data were tested using t-test, and P < 0.05 was considered statistically significant.

[0087] Experimental Results Comparison of disease activity and efficacy DAS28 efficacy assessment (see Table 1) Table 1 Comparison of the efficacy of DAS28 in each group

[0088] Note: All cases of rheumatoid arthritis (Qi and blood deficiency syndrome) enrolled in the study were from the Rheumatology Clinic and Ward of Chengdu Traditional Chinese Medicine Hospital from February 2022 to September 2023, with a total of 60 cases, who were randomly divided into experimental groups 1-3 and control groups 1-3, with 10 people in each group.

[0089] (2) Comparison of other clinical efficacy indicators between control group 1 and experimental group 2: Before treatment, there was no statistical difference in TJC, SJC, morning stiffness time, VAS, and HAQ scores between the two groups (P>0.05, see Table 2 and Table 3), and the baselines were comparable. After one month of treatment, the patients' TJC, SJC, morning stiffness time, VAS, and HAQ scores were significantly improved compared with those before treatment, with statistical differences (P<0.05, see Table 2 and Table 3). After one month of treatment, the therapeutic effect of TJC, SJC, morning stiffness time, VAS, and HAQ scores in the experimental group was better than that in the control group, with statistical differences (P<0.05, see Table 2 and Table 3).

[0090] Table 2 Comparison of TJC, SJC and morning stiffness time between the two groups

[0091]

[0092] Note: The independent sample rank sum test was used for inter-group comparison; the paired sample rank sum test was used for intra-group comparison. * P<0.05, comparison within experimental group△ P<0.05.

[0093] Table 3 Comparison of VAS and HAQ scores between the two groups

[0094]

[0095] Note: The independent sample rank sum test was used for inter-group comparison; the independent sample rank sum test was used for intra-group comparison. * P<0.05, comparison within experimental group △ P<0.05.

[0096] (3) TCM syndrome scores, main syndrome differentiation factors and comparison of efficacy Before treatment, there was no statistical difference in TCM syndrome scores and main syndrome differentiation factors between the two groups (P>0.05, see Table 4 and Table 5), and the baseline was comparable. After one month of treatment, the TCM syndrome scores and main syndrome differentiation factors (arthralgia, joint swelling, morning stiffness, spontaneous sweating, shortness of breath, fatigue, numbness) of the two groups of patients were significantly improved compared with before treatment, and the efficacy of the experimental group was better than that of the control group, with statistical differences (P<0.05, see Table 4 and Table 5), among which shortness of breath and fatigue had significant differences (P<0.01, see Table 5). After one month of treatment, the effective rate of TCM syndrome scores in the experimental group was 91.08%, which was higher than the effective rate of the control group of 36.51%, with statistical differences (P<0.05, see Table 5).

[0097] Table 4 Comparison of TCM syndrome scores between the two groups

[0098]

[0099] Note: The independent sample t test was used for comparison between groups; the paired sample t test was used for comparison within groups.

[0100] Table 5 Comparison of main syndrome differentiation factors between the two groups

[0101]

[0102] Note: The independent sample rank sum test was used for inter-group comparison; the independent sample rank sum test was used for intra-group comparison. * P<0.05, comparison within experimental group △ P<0.05.

[0103] Comparison of inflammatory factors between the two groups Before treatment, there was no statistical difference in TNF-α, IL-6, and IL-10 between the two groups (P>0.05, see Table 6 and Table 7), and the baseline was comparable. After one month of treatment, TNF-α and IL-6 in both groups improved, and the efficacy of the experimental group was better than that of the control group, with statistical difference (P<0.05, see Table 6), while IL-10 had no significant change, with no statistical difference (P>0.05, see Table 7).

[0104] Table 6 Comparison of proinflammatory cytokines between the two groups

[0105]

[0106] Note: The independent sample rank sum test was used for inter-group comparison; the independent sample rank sum test was used for intra-group comparison. * P<0.05, comparison within experimental group △ P<0.05.

[0107] Table 7 Comparison of anti-inflammatory cytokines between the two groups

[0108]

[0109] Note: The independent sample rank sum test was used for inter-group comparison; the independent sample rank sum test was used for intra-group comparison. * P<0.05, comparison within experimental group △ P<0.05.

[0110] (5) Safety evaluation After treatment, there were no obvious abnormalities or clinically significant changes in the routine blood and urine tests and liver and kidney function indicators of the two groups. No adverse reactions occurred, and safety was guaranteed.

[0111] IX. Results Analysis All cases of rheumatoid arthritis (Qi and blood deficiency syndrome) enrolled in the study were from the Rheumatology Clinic and Ward of Chengdu Hospital of Traditional Chinese Medicine from February 2023 to February 2024, with a total of 68 cases, who were randomly divided into an experimental group and a control group. After one month of treatment, 2 patients in the control group 1 and 3 patients in the experimental group 2 were free of the disease.

[0112] The freeze-dried powder product of the present invention has the same effect as the pure western medicine treatment of the control group 1, or even better effect, and the product adopts Chinese medicine preparation, and has less side effects. The fermentation process is used to treat the black-banded snake and the white-flowered snake, and the effective ingredients are released more completely.

[0113] All technical features in this embodiment can be modified in appearance according to actual needs.

[0114] The above embodiments are preferred implementation schemes of the present invention. In addition, the present invention may also be implemented in other ways. Any obvious replacement without departing from the concept of the present technical solution is within the protection scope of the present invention.

Claims

1. A freeze-dried powder of a pharmaceutical composition containing Garcinia charantia, characterized in that: The freeze-dried powder comprises the following raw materials in parts by weight: 500-1500 parts of black-banded snakes, 100-1000 parts of white-flowered snakes, 100-1000 parts of glutinous rice, 10-60 parts of distiller's yeast, 50-100 parts of motherwort, 30-80 parts of raw rehmannia root, 30-80 parts of patrinia herba, 30-80 parts of whiteheada, 20-60 parts of safflower and 50-100 parts of salvia miltiorrhiza.

2. A freeze-dried powder of a pharmaceutical composition containing Garuda according to claim 1, characterized in that: The koji is a mixture of red koji and white koji, two traditional Chinese medicines, in a weight ratio of 5:

1.

3. A method for preparing a freeze-dried powder of a pharmaceutical composition containing Garuda according to any one of claims 1-2, characterized in that: The following steps are involved: S1, removing the heads and internal organs of the cultivated black-banded snake and white-flowered snake, washing them with distilled water, steaming glutinous rice for 20 minutes and then cooling to 30° C.; mixing glutinous rice with the black-banded snake and white-flowered snake meat, and then adding sugar, distiller's yeast and mountain spring water for fermentation, and filtering to separate the fermentation liquid and solid matter for later use; S2, adding the compatible medicinal materials to the fermentation liquid separated in step S1 according to the proportion, sealing and soaking in a constant temperature and light-proof environment for 7 to 15 days, filtering and taking the soaking liquid for later use; S3, distilling and purifying the soaking liquid in step S2 to obtain a condensed distillate for standby use; S4, vacuum drying the solid material separated in step S1 and then crushing it to obtain a powder for later use; S5, adding the powder product in step S4 to the distillate obtained in step S3 to dissolve and mix evenly, freezing the mixed solution, vacuum dehydrating and drying, and then crushing it into powder for a second time to obtain freeze-dried snake powder.

4. A method for preparing a freeze-dried powder of a pharmaceutical composition containing Garuda according to claim 3, characterized in that: The fermentation temperature of step S1 is 30-38°C, and the fermentation time is 7-12 days.

5. A method for preparing a freeze-dried powder of a pharmaceutical composition containing Garuda according to claim 3, characterized in that: In step S3, the mixture is placed in a distillation device and heated to 78° C. for extraction.

6. A method for preparing a freeze-dried powder of a pharmaceutical composition containing Garuda according to claim 3, characterized in that: The conditions for processing the solid material in step S4 are: freezing condition -20~-25°C, vacuum condition 8Pa~13Pa.

7. A method for preparing a freeze-dried powder of a pharmaceutical composition containing Garuda according to claim 3, characterized in that: The specific method for preparing the freeze-dried powder of Garcinia charaxylata in step S5 comprises the following steps: S51, pre-freezing: cooling the mixed solution to -40~-45°C and maintaining it for 2~3 hours to completely freeze the mixed solution; S52, sublimation drying: turn on the vacuum pump, control the vacuum degree to 3.8Pa~7.6Pa, uniformly heat to -15~-20℃, keep warm for 1~2h, uniformly heat to -10~-8℃ again, keep warm for 5~7h; S53, secondary drying: continue to heat to 21~25℃, vacuum condition 0.8Pa~1.3Pa, maintain for 3~4h; S54, crushing, crushing the product dried in step S53, and packaging after sterilization to obtain the freeze-dried powder of the black-necked snake.

Images