Traditional Chinese medicine granule for treating chronic knee joint pain and preparation method thereof

Abstract

The invention discloses traditional Chinese medicine granules for treating chronic knee joint pain, which are prepared from the following raw materials in parts by weight: 20 to 30 parts of radix salviae miltiorrhizae, 15 to 25 parts of rhizoma chuanxiong, 10 to 20 parts of flos carthami, 8 to 12 parts of rhizoma pinelliae preparata, 15 to 25 parts of pericarpium citri reticulatae, 15 to 25 parts of radix peucedani, 12 to 18 parts of cortex phellodendri, 20 to 30 parts of fructus gardeniae, 15 to 25 parts of rhizoma polygoni cuspidati, 20 to 30 parts of radix astragali seu hedysari, 15 to 25 parts of rhizoma atractylodis macrocephalae, 8 to 12 parts of rhizoma alismatis, 15 to 25 parts of semen plantaginis and the like. The traditional Chinese medicine can promote blood circulation to remove blood stasis, eliminate dampness and phlegm, clear away heat and toxic materials, tonify lung qi, gasify water, tonify liver and kidney, nourish blood and soften tendons, tonify spleen and remove dampness, dredge meridians and tendons, regulate qi activity, eliminate dampness, dredge qi activity, regulate qi and blood and guide the downward movement of medicines, so that the chronic knee joint pain caused by pyretic arthralgia is treated together.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine preparations, and particularly relates to a traditional Chinese medicine granule for treating chronic knee pain and a preparation method thereof. Background Art

[0002] The causes of knee pain are relatively complex, including trauma, degenerative diseases, inflammatory diseases, etc. There are many diseases that cause joint pain, such as trauma, arthralgia due to wind, cold and dampness, arthralgia due to heat, gout, arthralgia due to wind and dampness complicated with deficiency, arthralgia due to cold pathogen invading the bone, and tuberculosis of the bone. Therefore, the pathogenesis is also different. The main pathogenesis is the obstruction of qi flow in the channels and collaterals, resulting in joint blockage, that is, "pain due to obstruction". There are also cases where the bone lacks nourishment, resulting in "pain due to deficiency of nourishment". The nature of the disease can be divided into cold, heat, deficiency and excess. At the initial stage of the disease, it is mostly excess, and in the long-term disease, it is mostly deficiency, often with a mixture of deficiency and excess. Trauma causes local qi and blood stasis in the joint, resulting in obstruction of qi flow in the channels; or deficiency of vital qi, blockage of the channels and collaterals by wind, cold and dampness arthralgia, and loss of nourishment of the tendons and vessels; or erosion by tuberculosis insects, depletion of qi and blood, resulting in blockage of qi and blood; or pathogenic toxins of warm epidemic diseases, penetrating into the nutrient blood and blocking the channels. Chronic joint pain is difficult to cure, recurring repeatedly for a long time, and requires long-term medication. At present, there is no specific drug in clinical practice. Clinically, non-steroidal anti-inflammatory drugs, analgesics and glucocorticoid drugs are mostly used for treatment. The medication time is long, and strong adverse reactions are likely to occur. Chemotherapy drugs will also show drug resistance, and the compliance of patients is relatively poor.

[0003] CN104606582B discloses a traditional Chinese medicine formula for treating rheumatic cold arthralgia, including the following raw materials by weight in grams: prepared monkshood root, prepared kusnezoff monkshood root, and asarum each 8-12 g, cinnamon twig, white peony root, dried ginger, licorice root, gentian, frankincense, myrrh, and angelica each 5-15 g, scorpion, taxillus twig, and turmeric each 10-20 g, salvia miltiorrhiza, psoralea corylifolia, drynaria rhizome, and millettia reticulata each 20-35 g, and centipede 8-15 g. The traditional Chinese medicine provided by the present invention can dispel wind and cold, and promote diuresis and dredge collaterals; when treating arthralgia due to wind, it has the advantages of quick onset, treating both the symptoms and the root cause, high cure rate, low recurrence rate, small dosage of medicine, short medication time, and low side effects on patients. Because it contains toxic drugs, there are potential safety hazards during the treatment process.

[0004] CN116763834B discloses a traditional Chinese medicine composition, preparation, preparation method and application for treating joint pain. The raw materials of the composition are composed of the following components: pyrola, dahurian angelica root, and licorice root. The preparation method includes ethanol extraction of pyrola, dahurian angelica root, and licorice root to obtain the product. Through the evaluation test of the anti-inflammatory and analgesic effects of mouse models of different process samples of the present invention, it is found that each process sample has certain analgesic and anti-inflammatory effects, and can be used for joint pain, scapulohumeral periarthritis, and pain caused by lumbar disc herniation. Among them, the ethanol extraction process is superior to the water extraction and water extraction and ethanol precipitation processes; when not adding alangium chinense, the anti-inflammatory and analgesic effects are significantly better than using the branches, and are equivalent to the effect of adding the roots of alangium chinense. The prescription of the present invention not only improves the anti-inflammatory drug effect, but also removes the toxic drug flavors, has higher safety, better drug effect, and avoids the problem of lack of resources of toxic drug flavors. It does not carry out syndrome differentiation and treatment for the syndrome types of joint pain, which is likely to lead to aggravation of symptoms. Summary of the invention

[0005] The purpose of the present invention is to provide a Chinese medicine granule for treating chronic knee joint pain.

[0006] Another object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine granules.

[0007] The purpose of the present invention is achieved through the following technical measures:

[0008] A Chinese medicine granule for treating chronic knee joint pain, wherein the raw materials of the Chinese medicine granule are composed of the following components by weight: 20-30 parts of salvia miltiorrhiza, 15-25 parts of chuanxiong, 10-20 parts of safflower, 8-12 parts of pinellia tuber, 15-25 parts of tangerine peel, 15-25 parts of peucedanum, 12-18 parts of phellodendron, 20-30 parts of gardenia, 15-25 parts of knotweed, 20-30 parts of astragalus, 15-25 parts of radix polygoni cuspidati, 20-30 parts of radix gardeniae, 15-25 parts of rhizoma polygonati, 20-30 parts of rhizoma scutellariae, 15-25 ... 0-30 parts, Atractylodes macrocephala 15-25 parts, Alisma orientalis 8-12 parts, Plantago seed 15-25 parts, Eucommia ulmoides 8-12 parts, Cuscuta australis 15-25 parts, Rehmannia glutinosa 10-20 parts, Lycopodiella cuneata 12-18 parts, Coix lachryma-jobi 15-25 parts, Magnolia officinalis 10-20 parts, Bupleurum 10-20 parts, Fructus Aurantii Immaturus 8-12 parts, Achyranthes bidentata 10-20 parts, Millettia spatholobi 15-25 parts.

[0009] The Chinese medicine granules for treating chronic knee joint pain are composed of the following components by weight: 25 parts of salvia miltiorrhiza, 20 parts of chuanxiong, 15 parts of safflower, 10 parts of pinellia tuber, 20 parts of dried tangerine peel, 20 parts of peucedanum, 15 parts of phellodendron, 25 parts of gardenia, 20 parts of polygonum cuspidatum, 25 parts of astragalus, 20 parts of atractylodes, 10 parts of orientalis, 20 parts of plantain seeds, 10 parts of eucommia, 20 parts of dodder seeds, 15 parts of rehmannia root, 15 parts of lycopodii herba, 20 parts of coix seeds, 15 parts of magnolia bark, 15 parts of bupleurum, 10 parts of fructus aurantii, 15 parts of achyranthes bidentata, and 20 parts of millettia reticulata.

[0010] The preparation method of the Chinese medicine granules for treating chronic knee joint pain comprises the following steps:

[0011] (1) extracting volatile oil from salvia miltiorrhiza, chuanxiong, safflower, dried orange peel and fructus aurantii by supercritical carbon dioxide extraction;

[0012] (2) combining the residue after extracting the volatile oil in step (1) with other Chinese medicinal materials, adding 2 times the amount of water to soak for 1 hour, adding 10 times the amount of water, decocting twice, each time for 1-3 hours, filtering, combining the filtrate, concentrating to an extract with a relative density of 1.15-1.25 at 80° C., drying at 60° C. and 0.07-0.08 MPa, and crushing into fine powder for standby use after drying;

[0013] (3) Take the fine powder obtained in step (2), spray the volatile oil obtained in step (1), and add auxiliary materials to prepare granules.

[0014] In the preparation method of the traditional Chinese medicine granule for treating chronic knee pain, in step (1), the conditions for supercritical carbon dioxide extraction are as follows: the extraction pressure is 25 - 35 MPa, the extraction temperature is 70 - 75 °C, the pressure of the separation column is 22 - 25 MPa, the temperature is 30 - 50 °C, the pressure of the separation kettle is 6 - 10 MPa, the temperature is 30 - 40 °C, and the extraction and separation time is 2 - 4 hours.

[0015] In the preparation method of the traditional Chinese medicine granule for treating chronic knee pain, in step (1), the conditions for supercritical carbon dioxide extraction are as follows: the extraction pressure is 30 MPa, the extraction temperature is 72 °C, the pressure of the separation column is 24 MPa, the temperature is 40 °C, the pressure of the separation kettle is 8 MPa, the temperature is 35 °C, and the extraction and separation time is 3 hours.

[0016] In the preparation method of the traditional Chinese medicine granule for treating chronic knee pain, the excipients in step (1) are lactose, hydroxypropyl methylcellulose and polyvinylpyrrolidone. In step (3), the total weight ratio of the fine powder and volatile oil to lactose, hydroxypropyl methylcellulose and polyvinylpyrrolidone is 100:10:20:10. Polyvinylpyrrolidone is used as a binder and is dissolved with an appropriate amount of water.

[0017] Use of the traditional Chinese medicine granule for treating chronic knee pain in the preparation of a medicament for treating chronic knee pain.

[0018] Use of the traditional Chinese medicine granule for treating chronic knee pain in the preparation of a medicament for treating chronic knee pain, and the chronic knee pain belongs to the type of heat arthralgia syndrome.

[0019] Lycopodium clavatum is the dried whole herb of Lycopodium japonicum Thunb. of the genus Lycopodium in the family Lycopodiaceae. It is harvested in summer and autumn when the stems and leaves are lush, impurities are removed, and it is dried in the sun. It has the effects of expelling wind and removing dampness, and relaxing muscles and tendons. It is used for joint soreness and limited flexion and extension. The rest of the medicinal materials all meet the standards of the Chinese Pharmacopoeia.

[0020] Knee pain belongs to the category of knee bi-syndrome in traditional Chinese medicine. At the initial stage of bi-syndrome, exogenous pathogenic factors of wind-cold-damp-heat often invade the human body when it is deficient, blocking the meridian qi and blood, mainly with excess pathogenic factors. If it recurs repeatedly or develops gradually, in chronic knee pain, due to the long-term obstruction of the meridians by pathogenic qi, the nutrient qi and defensive qi cannot circulate smoothly, dampness accumulates into phlegm, and the collaterals are blocked by stasis, with phlegm and stasis interacting with each other. Clinically, heat bi-syndrome is more common. The clinical manifestations are: pain in the limb joints, the affected area is red, hot, swollen and painful severely, the tendons and vessels are cramped, the hand cannot approach it, and it is even more difficult to get out of bed. The pain is worse at night and lighter during the day. Patients usually have symptoms such as fever, thirst, restlessness, and preference for cold over heat. The tongue is red, the tongue coating is yellow and dry, and the pulse is slippery and rapid. Heat is a yang pathogenic factor, with an urgent nature. After invading the meridians and joints of the human body, it clashes with the qi and blood of the human body. Due to the cramped tendons and vessels and the obstruction of the meridians by stasis, severe pain occurs. The redness, heat, swelling and pain in the affected area, as well as fever, thirst, restlessness, rapid pulse, red tongue and yellow coating, are all the characteristics of fire-heat, and also reflect the characteristic that fire-heat is most likely to consume body fluid.

[0021] Due to the long-term obstruction of qi and blood in the meridians, under the action of pathogenic factors, stasis and phlegm turbidity often occur. Phlegm remains in the joints and stasis blocks the meridians, aggravating the bi-obstruction, causing qi and blood to lose nourishment. Pain, numbness, swelling can be seen, and even joint deformity and limited movement may occur. Ordinary herbs for expelling wind, dispersing cold and removing dampness are ineffective, because joint swelling and pain are mostly caused by the flow of tangible pathogenic factors and the mutual obstruction of phlegm and stasis. Zhang Jingyue in "Complete Works of Jingyue - Wind Bi-syndrome" believed that although bi-syndrome generally follows the pattern of wind-cold-damp combined bi-syndrome, it must be differentiated into yin syndrome and yang syndrome, and yang syndrome is heat bi-syndrome. "Those with fire should be treated with coolness, and those with cold should be treated with warmth", but he thought that bi-syndrome is indeed "more cases of cold and fewer cases of heat". This was much criticized by warm disease scholars in the Qing Dynasty. Wu Jutong in "Treatise on Febrile Diseases - Dampness-warmth in the Middle Jiao" loudly exclaimed: "Bi-syndrome is indeed mostly caused by cold, but there are also quite a few cases complicated with heat." The harm of misusing pungent-warm herbs will be immediately seen. Ye Tianshi in "Medical Records of Clinical Practice" had incisive discussions on the pathogenesis and treatment methods of heat bi-syndrome: "Bi-syndrome has always been mainly treated with the three exogenous pathogenic factors of wind-cold-damp. The differences in symptoms are due to the exogenous damp-heat added by summer heat, and the endogenous damp-heat accumulated from food and water. The exogenous pathogenic factors attach to the meridians, and the endogenous pathogenic factors attach to the zang-fu collaterals. Therefore, sweating with pungent herbs does not reduce the heat pain. I used to clear the Yangming meridian urgently and achieved slight improvement" (Case of Shen in Volume Seven - Bi-syndrome). This clearly points out that the etiologies and treatment methods of damp-heat bi-syndrome and wind-cold-damp bi-syndrome are different. Gu Songyuan in "Medical Mirror" further stated that heat bi-syndrome can not only be caused by the invasion of damp-heat pathogenic factors, but also for wind-cold-damp bi-syndrome, "when the pathogenic factors are stagnated and the disease lasts for a long time, wind turns into fire, cold turns into heat, and damp turns into phlegm", which is also heat bi-syndrome. Therefore, in this invention, Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius for promoting blood circulation and removing stasis, Pinellia ternata, Citrus reticulata, Peucedanum praeruptorum for drying dampness and resolving phlegm, Phellodendron amurense, Gardenia jasminoides, Polygonum cuspidatum for clearing heat and detoxifying are used together as the monarch herbs.

[0022] The occurrence and development of bi syndrome involve the five zang-organs of the liver, heart, lung, spleen, and kidney, and its pathogenesis is also complex and changeable. However, from the prominent manifestations of aversion to cold and fever, joint swelling in the acute stage and joint swelling and pain in the chronic stage, it is closely related to the lung. As stated in "Classified Treatises of Syndromes - Bi Syndrome", "Qi is blocked by pathogenic factors and cannot circulate smoothly, thus stagnating", resulting in the accumulation of refined grains of water and food turning into phlegm-fluid, blocking the muscles and joints, manifested as numbness, swelling, and severe pain. Phlegm-fluid, retained fluid, and dampness can block qi and blood, filling the muscles and joints, leading to pain due to obstruction. Therefore, the swelling and pain are consistent with the degree of phlegm-fluid accumulation. This is true for wind-cold-damp bi syndrome, and for wind-damp-heat bi syndrome, it can also be caused by damp pathogen blocking the water passages and heat pathogen boiling body fluids into phlegm, resulting in local phlegm-fluid accumulation in the joints. Astragalus membranaceus, Atractylodes macrocephala, Alisma orientale, and Plantago asiatica are selected as assistant drugs to promote the excretion of phlegm-fluid through urination by tonifying the lung qi and promoting qi transformation of body fluids.

[0023] As the disease progresses and enters the deeper stage, qi and blood are depleted, the liver and kidneys are damaged, and the muscles and bones lose nourishment, thus resulting in a syndrome of healthy qi deficiency and lingering pathogen, mainly manifested by healthy qi deficiency. Generally, new diseases are mostly excessive in nature, while chronic diseases are mostly deficient. However, this is only in general cases. Clinically, it is not uncommon to see cases where the liver, kidneys, qi, and blood are deficient first, and then affected by external pathogens, presenting a syndrome mainly of deficiency or a syndrome of deficiency in the root and excess in the branch from the very beginning; and although the course of the disease lasts for several months or years, or is prolonged by cold-dampness, or damp-heat flowing downward, or phlegm-stasis binding, with intermingled deficiency and excess, and mainly manifested by excess pathogen, this is also commonly seen. Eucommia ulmoides, Cuscuta chinensis are selected to tonify the liver and kidneys, and Rehmannia glutinosa, Lycopodium clavatum are used to nourish the blood and soothe the tendons, all of which are assistant drugs.

[0024] The spleen and stomach are the foundation of acquired constitution. Deficiency of healthy qi often involves the spleen and stomach, and patients with bi syndrome need to take Chinese and Western medicines for a long time due to the long course of the disease, and are most likely to be damaged by drug toxicity to the spleen and stomach. Damage to the spleen and stomach will make the recovery of bi syndrome even worse. The grain qi of the spleen and stomach is rooted in the congenital invisible yin and yang, and is more transformed into the acquired visible qi and blood. Regulating the spleen and stomach can generate qi and blood, moisten and nourish the whole body, and when the middle qi is harmonized, the five zang-organs will be at peace. The spleen generates the lung, that is, earth generates metal. For example, when the spleen qi transports and transforms, it generates qi to nourish the lung. Tonifying the spleen and stomach helps the assistant drugs to tonify the lung qi and promote qi transformation of body fluids. Coix lacryma-jobi and Magnolia officinalis are selected and used together with the above drugs for tonifying the liver and kidneys as assistant drugs. Among them, Coix lacryma-jobi has the effects of strengthening the spleen and promoting diuresis, dredging the tendons, and Magnolia officinalis regulates qi movement and eliminates dampness.

[0025] When qi stagnation is relatively severe in bi syndrome, qi movement is not smooth and the meridians are blocked. At this time, the method of promoting qi circulation and dredging the meridians uses drugs with the effect of promoting qi circulation, such as Bupleurum chinense and Aurantii Fructus Immaturus in the present invention, to dredge qi movement, regulate qi and blood, and thus relieve bi pain. Achyranthes bidentata and Spatholobus suberectus are used to lead the drugs downward, and the four of them are all guiding drugs.

[0026] The whole formula of the present invention contains Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Pinellia ternata, Citrus reticulata Blanco, Peucedanum praeruptorum Dunn, Phellodendron amurense Rupr., Gardenia jasminoides Ellis, Polygonum cuspidatum Sieb. et Zucc., Astragalus membranaceus (Fisch.) Bunge, Atractylodes macrocephala Koidz., Alisma orientale (Sam.) Juz., Plantago asiatica L., Eucommia ulmoides Oliv., Cuscuta chinensis Lam., Rehmannia glutinosa (Gaertn.) Libosch. f. hueichingensis (Chao et Schih) Hsiao et Keng, Lycopodium clavatum L., Coix lacryma-jobi L., Magnolia officinalis Rehd. et Wils., Bupleurum chinense DC., Aurantii Fructus Immaturus, Achyranthes bidentata Blume, and Spatholobus suberectus Dunn. It can promote blood circulation to remove blood stasis, dry dampness and resolve phlegm, clear heat and detoxify, tonify the lung qi, promote qi transformation of body fluids, tonify the liver and kidney, nourish blood and relax tendons, strengthen the spleen and promote diuresis, dredge the tendons, regulate qi movement, eliminate dampness, dredge qi movement, regulate qi and blood, and guide the drug downward, jointly achieving the treatment of chronic knee pain of the heat arthralgia syndrome type.

[0027] The stability study shows that the granules (Examples 1 - 3) prepared with lactose, hydroxypropyl methylcellulose, and polyvinylpyrrolidone as excipients in the present invention do not change in appearance and are not prone to moisture absorption after 6 months of accelerated stability; the granules (Comparative Example 1) prepared with only lactose as the excipient change in appearance after 6 months of accelerated stability, do not show caking, but are prone to moisture absorption; the granules (Comparative Example 2) prepared with only hydroxypropyl methylcellulose as the excipient change in appearance after 6 months of accelerated stability, show caking, and are also prone to moisture absorption; the granules (Comparative Examples 3 - 4) prepared with dextrin or starch as the excipient change in appearance after 6 months of accelerated stability, show caking, and are also prone to moisture absorption, indicating that the selection of excipients in the present invention is reasonable and can improve the stability of the granules.

[0028] The pharmacodynamic study shows that the granules of the present invention have an analgesic effect of reducing the pain threshold and prolonging the pain latency in normal mice. It can also reduce the permeability of peritoneal capillaries in mice and has an anti - inflammatory effect comparable to that of the positive drug Zhuanggu Guanjie Pills. For the rats with wind - heat arthralgia syndrome model, it can reduce the plantar volume (P < 0.05), and significantly reduce the levels of TNF - α and IL - 1β in the rats with wind - heat arthralgia syndrome model, indicating that the present invention has an obvious anti - inflammatory effect.

[0029] The clinical study shows that in the control group, 13 cases were cured, 12 cases were markedly effective, 16 cases were effective, and 9 cases were ineffective, with an effective rate of 82%; in the group of the present invention, 25 cases were cured, 17 cases were markedly effective, 5 cases were effective, and 3 cases were ineffective, with an effective rate of 94%. The effect of Example 1 group of the present invention is significantly better than that of the control drug group, indicating that the compatibility of the present invention is reasonable and can treat chronic knee pain of the heat arthralgia syndrome type. Detailed implementation manners

[0030] The present invention will be further described below in conjunction with specific implementation manners. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content described in the present invention, those skilled in the art can make various changes or modifications to the present invention, but these equivalent forms also fall within the scope defined by the appended claims of this application.

[0031] Example 1: Take 25 g of Salvia miltiorrhiza, 20 g of Ligusticum chuanxiong, 15 g of Carthamus tinctorius, 10 g of Pinellia ternata, 20 g of Citrus reticulata Blanco, 20 g of Peucedanum praeruptorum Dunn, 15 g of Phellodendron amurense Rupr., 25 g of Gardenia jasminoides Ellis, 20 g of Polygonum cuspidatum Sieb. et Zucc., 25 g of Astragalus membranaceus (Fisch.) Bunge, 20 g of Atractylodes macrocephala Koidz., 10 g of Alisma orientale (Sam.) Juz., 20 g of Plantago asiatica L., 10 g of Eucommia ulmoides Oliv., 20 g of Cuscuta chinensis Lam., 15 g of Rehmannia glutinosa Libosch. f. hueichingensis (Chao) Hsiao & Keng, 15 g of Lycopodium clavatum L., 20 g of Coix lacryma-jobi L., 15 g of Magnolia officinalis Rehd. et Wils., 15 g of Bupleurum chinense DC., 10 g of Aurantii Fructus Immaturus, 15 g of Achyranthes bidentata Blume, 20 g of Spatholobus suberectus Dunn, and the preparation method includes the following steps;

[0032] (1) Take Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Citrus reticulata Blanco, and Aurantii Fructus Immaturus, and extract the volatile oil by carbon dioxide supercritical extraction. The conditions are as follows: the extraction pressure is 30 MPa, the extraction temperature is 72 °C, the separation column pressure is 24 MPa, the temperature is 40 °C, the separation kettle pressure is 8 MPa, the temperature is 35 °C, and the extraction and separation time is 3 hours;

[0033] (2) Combine the medicinal residues after extracting the volatile oil in step (1) with other traditional Chinese medicine raw materials, soak them in 2 times the amount of water for 1 h, add 10 times the amount of water, decoct them 2 times, each time for 2 h, filter, combine the filtrates, concentrate them to an extract with a relative density of 1.20 at 80 °C, and dry them in an environment of 60 °C and 0.075 Mpa. After drying, pulverize them into fine powder for standby;

[0034] (3) Take the fine powder prepared in step (2), spray in the volatile oil prepared in step (1), add lactose, hydroxypropyl methylcellulose, and polyvinylpyrrolidone. The weight ratio of the total weight of the fine powder and the volatile oil to lactose, hydroxypropyl methylcellulose, and polyvinylpyrrolidone in step (3) is 100:10:20:10. Polyvinylpyrrolidone is used as a binder and dissolved in an appropriate amount of water to prepare a granule.

[0035] Example 2:

[0036] Take 20 g of Salvia miltiorrhiza, 25 g of Ligusticum chuanxiong, 10 g of Carthamus tinctorius, 12 g of Pinellia ternata, 15 g of Citrus reticulata Blanco, 25 g of Peucedanum praeruptorum Dunn, 12 g of Phellodendron amurense Rupr., 30 g of Gardenia jasminoides Ellis, 15 g of Polygonum cuspidatum Sieb. et Zucc., 30 g of Astragalus membranaceus (Fisch.) Bunge, 15 g of Atractylodes macrocephala Koidz., 12 g of Alisma orientale (Sam.) Juz., 15 g of Plantago asiatica L., 12 g of Eucommia ulmoides Oliv., 15 g of Cuscuta chinensis Lam., 20 g of Rehmannia glutinosa Libosch. f. hueichingensis (Chao) Hsiao & Keng, 12 g of Lycopodium clavatum L., 25 g of Coix lacryma-jobi L., 10 g of Magnolia officinalis Rehd. et Wils., 20 g of Bupleurum chinense DC., 8 g of Aurantii Fructus Immaturus, 20 g of Achyranthes bidentata Blume, 15 g of Spatholobus suberectus Dunn, and the preparation method includes the following steps;

[0037] (1) Take Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Citrus reticulata Blanco, and Aurantii Fructus Immaturus, and extract the volatile oil by carbon dioxide supercritical extraction. The conditions are as follows: the extraction pressure is 25 MPa, the extraction temperature is 75 °C, the separation column pressure is 22 MPa, the temperature is 50 °C, the separation kettle pressure is 6 MPa, the temperature is 40 °C, and the extraction and separation time is 2 hours;

[0038] (2) Combine the medicinal residues after extracting volatile oil in step (1) with other important raw materials, soak them in 2 times the amount of water for 1 h, add 10 times the amount of water, decoct twice, each time for 1 h, filter, combine the filtrates, concentrate to an extract with a relative density of 1.25 at 80 °C, dry in an environment of 60 °C and 0.07 Mpa, and pulverize into fine powder for standby after drying;

[0039] (3) Take the fine powder prepared in step (2), spray in the volatile oil prepared in step (1), add lactose, hydroxypropyl methylcellulose and polyvinylpyrrolidone. The weight ratio of the total weight of the fine powder and volatile oil in step (3) to lactose, hydroxypropyl methylcellulose and polyvinylpyrrolidone is 100:10:20:10. Polyvinylpyrrolidone is used as a binder, dissolved in an appropriate amount of water, and made into granules.

[0040] Example 3:

[0041] Take 30 g of Salvia miltiorrhiza, 15 g of Ligusticum chuanxiong, 20 g of Carthamus tinctorius, 8 g of Pinellia ternata, 25 g of Citrus reticulata Blanco, 15 g of Peucedanum praeruptorum Dunn, 18 g of Phellodendron amurense Rupr., 20 g of Gardenia jasminoides Ellis, 25 g of Polygonum cuspidatum Sieb. et Zucc., 20 g of Astragalus membranaceus (Fisch.) Bunge, 25 g of Atractylodes macrocephala Koidz., 8 g of Alisma orientale (Sam.) Juz., 25 g of Plantago asiatica L., 8 g of Eucommia ulmoides Oliv., 25 g of Cuscuta chinensis Lam., 10 g of Rehmannia glutinosa Libosch. f. hueichingensis (Chao) Hsiao et Keng, 18 g of Lycopodium clavatum L., 15 g of Coix lacryma-jobi L., 20 g of Magnolia officinalis Rehd. et Wils., 10 g of Bupleurum chinense DC., 12 g of Aurantii Fructus Immaturus, 10 g of Achyranthes bidentata Blume, 25 g of Spatholobus suberectus Dunn, and the preparation method includes the following steps;

[0042] (1) Take Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Citrus reticulata Blanco, and Aurantii Fructus Immaturus, and extract volatile oil by carbon dioxide supercritical extraction. The conditions are: extraction pressure is 35 MPa, extraction temperature is 70 °C, separation column pressure is 25 MPa, temperature is 30 °C, separation kettle pressure is 10 MPa, temperature is 30 °C, and extraction and separation time is 4 hours;

[0043] (2) Combine the medicinal residues after extracting volatile oil in step (1) with other important raw materials, soak them in 2 times the amount of water for 1 h, add 10 times the amount of water, decoct twice, each time for 3 h, filter, combine the filtrates, concentrate to an extract with a relative density of 1.15 at 80 °C, dry in an environment of 60 °C and 0.08 Mpa, and pulverize into fine powder for standby after drying;

[0044] (3) Take the fine powder prepared in step (2), spray in the volatile oil prepared in step (1), add lactose, hydroxypropyl methylcellulose and polyvinylpyrrolidone. The weight ratio of the total weight of the fine powder and volatile oil in step (3) to lactose, hydroxypropyl methylcellulose and polyvinylpyrrolidone is 100:10:20:10. Polyvinylpyrrolidone is used as a binder, dissolved in an appropriate amount of water, and made into granules.

[0045] Comparative Example 1:

[0046] Take 25 g of Salvia miltiorrhiza, 20 g of Ligusticum chuanxiong, 15 g of Carthamus tinctorius, 10 g of Pinellia ternata, 20 g of Citrus reticulata Blanco, 20 g of Peucedanum praeruptorum Dunn, 15 g of Phellodendron amurense Rupr., 25 g of Gardenia jasminoides Ellis, 20 g of Polygonum cuspidatum Sieb. et Zucc., 25 g of Astragalus membranaceus (Fisch.) Bunge, 20 g of Atractylodes macrocephala Koidz., 10 g of Alisma orientale (Sam.) Juz., 20 g of Plantago asiatica L., 10 g of Eucommia ulmoides Oliv., 20 g of Cuscuta chinensis Lam., 15 g of Rehmannia glutinosa Libosch., 15 g of Lycopodium clavatum L., 20 g of Coix lacryma-jobi L., 15 g of Magnolia officinalis Rehd. et Wils., 15 g of Bupleurum chinense DC., 10 g of Aurantii Fructus Immaturus, 15 g of Achyranthes bidentata Blume, 20 g of Spatholobus suberectus Dunn, and the preparation method comprises the following steps;

[0047] (1) Take Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Citrus reticulata Blanco, and Aurantii Fructus Immaturus, and extract volatile oil by carbon dioxide supercritical extraction. The conditions are as follows: the extraction pressure is 30 MPa, the extraction temperature is 72 °C, the separation column pressure is 24 MPa, the temperature is 40 °C, the separation kettle pressure is 8 MPa, the temperature is 35 °C, and the extraction and separation time is 3 hours;

[0048] (2) Combine the medicinal residues after extracting volatile oil in step (1) with other traditional Chinese medicine raw materials, soak them in 2 times the amount of water for 1 h, add 10 times the amount of water, decoct twice, each time for 2 h, filter, combine the filtrates, concentrate to an extract with a relative density of 1.20 at 80 °C, and dry in an environment of 60 °C and 0.075 Mpa. After drying, pulverize it into fine powder for standby;

[0049] (3) Take the fine powder prepared in step (2), spray the volatile oil prepared in step (1), add lactose and polyvinylpyrrolidone. The weight ratio of the total weight of the fine powder and volatile oil to lactose and polyvinylpyrrolidone in step (3) is 100:10:10. Polyvinylpyrrolidone is used as a binder and dissolved with an appropriate amount of water to prepare granules.

[0050] Comparative Example 2: Take 25 g of Salvia miltiorrhiza, 20 g of Ligusticum chuanxiong, 15 g of Carthamus tinctorius, 10 g of Pinellia ternata, 20 g of Citrus reticulata Blanco, 20 g of Peucedanum praeruptorum Dunn, 15 g of Phellodendron amurense Rupr., 25 g of Gardenia jasminoides Ellis, 20 g of Polygonum cuspidatum Sieb. et Zucc., 25 g of Astragalus membranaceus (Fisch.) Bunge, 20 g of Atractylodes macrocephala Koidz., 10 g of Alisma orientale (Sam.) Juz., 20 g of Plantago asiatica L., 10 g of Eucommia ulmoides Oliv., 20 g of Cuscuta chinensis Lam., 15 g of Rehmannia glutinosa Libosch., 15 g of Lycopodium clavatum L., 20 g of Coix lacryma-jobi L., 15 g of Magnolia officinalis Rehd. et Wils., 15 g of Bupleurum chinense DC., 10 g of Aurantii Fructus Immaturus, 15 g of Achyranthes bidentata Blume, 20 g of Spatholobus suberectus Dunn, and the preparation method comprises the following steps;

[0051] (1) Take Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Citrus reticulata Blanco, and Aurantii Fructus Immaturus, and extract volatile oil by carbon dioxide supercritical extraction. The conditions are as follows: the extraction pressure is 30 MPa, the extraction temperature is 72 °C, the separation column pressure is 24 MPa, the temperature is 40 °C, the separation kettle pressure is 8 MPa, the temperature is 35 °C, and the extraction and separation time is 3 hours;

[0052] (2) Combine the medicinal residues after extracting volatile oil in step (1) with other traditional Chinese medicine raw materials, soak them in 2 times the amount of water for 1 h, then add 10 times the amount of water, decoct twice, each time for 2 h, filter, combine the filtrates, concentrate to an extract with a relative density of 1.20 at 80 °C, dry in an environment of 60 °C and 0.075 Mpa, and pulverize into fine powder for later use after drying;

[0053] (3) Take the fine powder prepared in step (2), spray in the volatile oil prepared in step (1), add hydroxypropyl methylcellulose and polyvinylpyrrolidone. The weight ratio of the total weight of the fine powder and the volatile oil in step (3) to the weights of hydroxypropyl methylcellulose and polyvinylpyrrolidone is 100:20:10. Polyvinylpyrrolidone is used as a binder and dissolved in an appropriate amount of water to prepare a granule.

[0054] Comparative Example 3:

[0055] Take 25 g of Salvia miltiorrhiza, 20 g of Ligusticum chuanxiong, 15 g of Carthamus tinctorius, 10 g of Pinellia ternata, 20 g of Citrus reticulata Blanco, 20 g of Peucedanum praeruptorum Dunn, 15 g of Phellodendron amurense Rupr., 25 g of Gardenia jasminoides Ellis, 20 g of Polygonum cuspidatum Sieb. et Zucc., 25 g of Astragalus membranaceus (Fisch.) Bunge, 20 g of Atractylodes macrocephala Koidz., 10 g of Alisma orientale (Sam.) Juz., 20 g of Plantago asiatica L., 10 g of Eucommia ulmoides Oliv., 20 g of Cuscuta chinensis Lam., 15 g of Rehmannia glutinosa Libosch. f. hueichingensis (Chao) Hsiao & Keng, 15 g of Lycopodium clavatum L., 20 g of Coix lacryma-jobi L. var. ma-yuen (Roman.) Stapf, 15 g of Magnolia officinalis Rehd. et Wils., 15 g of Bupleurum chinense DC., 10 g of Aurantii Fructus Immaturus, 15 g of Achyranthes bidentata Blume, 20 g of Spatholobus suberectus Dunn, and the preparation method includes the following steps;

[0056] (1) Take Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Citrus reticulata Blanco, and Aurantii Fructus Immaturus, and extract volatile oil by carbon dioxide supercritical extraction. The conditions are: extraction pressure is 30 MPa, extraction temperature is 72 °C, separation column pressure is 24 MPa, temperature is 40 °C, separation kettle pressure is 8 MPa, temperature is 35 °C, and extraction and separation time is 2 hours;

[0057] (2) Combine the medicinal residues after extracting volatile oil in step (1) with other important raw materials, soak them in 2 times the amount of water for 1 h, then add 10 times the amount of water, decoct twice, each time for 2 h, filter, combine the filtrates, concentrate to an extract with a relative density of 1.20 at 80 °C, dry in an environment of 60 °C and 0.075 Mpa, and pulverize into fine powder for later use after drying;

[0058] (3) Take the fine powder prepared in step (2), spray in the volatile oil prepared in step (1), add dextrin, and use 80% ethanol as a binder to prepare a granule.

[0059] Comparative Example 4:

[0060] Take 25 g of Salvia miltiorrhiza, 20 g of Ligusticum chuanxiong, 15 g of Carthamus tinctorius, 10 g of Pinellia ternata, 20 g of Citrus reticulata Blanco, 20 g of Peucedanum praeruptorum Dunn, 15 g of Phellodendron amurense Rupr., 25 g of Gardenia jasminoides Ellis, 20 g of Polygonum cuspidatum Sieb. et Zucc., 25 g of Astragalus membranaceus (Fisch.) Bunge, 20 g of Atractylodes macrocephala Koidz., 10 g of Alisma orientale (Sam.) Juz., 20 g of Plantago asiatica L., 10 g of Eucommia ulmoides Oliv., 20 g of Cuscuta chinensis Lam., 15 g of Rehmannia glutinosa Libosch. f. hueichingensis (Chao) Hsiao & Keng, 15 g of Lycopodium clavatum L., 20 g of Coix lacryma-jobi L., 15 g of Magnolia officinalis Rehd. et Wils., 15 g of Bupleurum chinense DC., 10 g of Aurantii Fructus Immaturus, 15 g of Achyranthes bidentata Blume, 20 g of Spatholobus suberectus Dunn, and the preparation method comprises the following steps;

[0061] (1) Take Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Citrus reticulata Blanco, and Aurantii Fructus Immaturus, and extract volatile oil by supercritical carbon dioxide extraction. The conditions are as follows: the extraction pressure is 30 MPa, the extraction temperature is 72 °C, the separation column pressure is 24 MPa, the temperature is 40 °C, the separation kettle pressure is 8 MPa, the temperature is 35 °C, and the extraction and separation time is 2 hours;

[0062] (2) Combine the medicinal residues after extracting volatile oil in step (1) with other important raw materials, soak them in 2 times the amount of water for 1 h, add 10 times the amount of water, decoct twice, each time for 2 h, filter, combine the filtrates, concentrate to an extract with a relative density of 1.20 at 80 °C, and dry it in an environment of 60 °C and 0.075 Mpa. After drying, pulverize it into fine powder for standby;

[0063] (3) Take the fine powder prepared in step (2), spray in the volatile oil prepared in step (1), add starch, and use 80% ethanol as a binder to prepare granules.

[0064] Example 4: Stability study

[0065] Take the granules prepared in Examples 1-3 and Comparative Examples 1-4, place them at 40 ± 2 °C and a relative humidity of 75 ± 5% for 6 months respectively for accelerated stability testing, sample at the 0th, 1st, 2nd, 3rd, and 6th months respectively, and conduct quality inspection. The measurement results are shown in Table 1 below:

[0066] Table 1 Results of accelerated stability testing of the granules of the present invention

[0067]

[0068] As can be seen from Table 1, for the granules prepared with lactose, hydroxypropyl methylcellulose and polyvinylpyrrolidone as excipients in the present invention (Examples 1 - 3), their properties do not change and they are not prone to moisture absorption during 6 - month accelerated stability; for the granules with only lactose as excipient (Comparative Example 1), their properties change during 6 - month accelerated stability, there is no caking phenomenon, but they are prone to moisture absorption; for the granules with only hydroxypropyl methylcellulose as excipient (Comparative Example 2), their properties change during 6 - month accelerated stability, caking phenomenon appears, and they are also prone to moisture absorption; for the granules with dextrin or starch as excipient (Comparative Examples 3 - 4), their properties change during 6 - month accelerated stability, caking phenomenon appears, and they are also prone to moisture absorption. This shows that the selection of excipients in the present invention is reasonable and can improve the stability of the granules.

[0069] Example 5: Pharmacodynamic study

[0070] 5.1 Influence of the present invention on the analgesic effect of normal mice by the writhing method

[0071] Fifty mice, both male and female, were randomly divided into 5 groups with 10 mice in each group. The gavage administration was as follows: the normal saline group (Group A) was 20 mL / kg; the positive drug group (Zhuanggu Guanjie Pills, China Resources Sanjiu Medical & Pharmaceutical Co., Ltd.; Approval No. Z44023377) had a dose of 1 g / kg; the low - dose group of the granules of Example 1 of the present invention had a dose of 5 g / kg; the medium - dose group of the granules of Example 1 of the present invention had a dose of 10 g / kg; the high - dose group of the granules of Example 1 of the present invention had a dose of 20 g / kg, once a day for 7 consecutive days. 30 minutes after the last administration, 0.6% acetic acid solution was intraperitoneally injected (10 mL / kg). The time of the first appearance of the writhing response of the mice was observed, and the number of writhing responses within 20 minutes was recorded. The above results were respectively subjected to t - test. The results are shown in Table 2.

[0072] Table 2 Influence of the granules of the present invention on the pain sensation of mice (x ± s)

[0073] Group Time of first appearance (min) Number of writhing times (times) Normal saline group 8.57±2.69 14.91±8.28 Positive drug group <![CDATA[12.82±5.48 * > <![CDATA[8.65±3.41 * > Low dose group <![CDATA[11.56±6.09 * > <![CDATA[9.42±3.98 * > Medium dose group <![CDATA[13.23±5.38 * > <![CDATA[8.98±4.16 * > High dose group <![CDATA[14.44±5.18 *# > <![CDATA[7.47±3.74 **# >

[0074] Compared with the normal saline group, ** P < 0.01, * P < 0.05; compared with the positive drug group, # P < 0.05.

[0075] As can be seen from the results in Table 2, the granules prepared in Example 1 of the present invention have an analgesic effect of reducing the pain threshold and prolonging the pain latency for normal mice.

[0076] 5.2 Influence of the present invention on the permeability of peritoneal capillaries in normal mice

[0077] Fifty mice, both male and female, were randomly divided into 5 groups of 10 mice each. The gavage administration was as follows: the normal saline group (Group A) received 20 mL / kg; the positive drug group (Zhuanggu Guanjie Pills, China Resources Sanjiu Medical & Pharmaceutical Co., Ltd.; Approval No. Z44023377) received a dose of 1 g / kg; the low-dose group of the granule of Example 1 of the present invention received a dose of 5 g / kg; the medium-dose group of the granule of Example 1 of the present invention received a dose of 10 g / kg; the high-dose group of the granule of Example 1 of the present invention received a dose of 20 g / kg. Administration was once a day for 7 consecutive days. 30 minutes after the last administration, 0.1 mL of Evans blue saline solution was injected into the tail vein at a dose of 0.1 mL / 10 g, and immediately 0.2 mL of 0.6% acetic acid was injected intraperitoneally per mouse. 20 minutes later, the mice were sacrificed by decapitation, the abdominal cavity was opened and rinsed, the washing fluid was collected, centrifuged for 5 minutes (1000 r / min), and the optical density (OD) value was measured at a wavelength of 590 nm using a UV-7542 ultraviolet spectrophotometer, and a t-test was performed. The results are shown in Table 3.

[0078] Table 3 Effect of the granule of the present invention on the permeability of peritoneal capillaries in mice (x±s)

[0079] Group OD value of peritoneal lavage fluid Normal saline group 0.576±0.043 Positive drug group <![CDATA[0.418±0.027 * > Low dose group <![CDATA[0.432±0.018 * > Medium dose group <![CDATA[0.421±0.034 * > High dose group <![CDATA[0.387±0.026 ** >

[0080] As can be seen from the results in Table 3, the granule prepared in Example 1 of the present invention can reduce the permeability of peritoneal capillaries in normal mice and has an anti-inflammatory effect comparable to that of the positive drug group of Zhuanggu Guanjie Pills.

[0081] 5.3 Study on the anti-inflammatory effect of the present invention on rats with wind-heat arthralgia syndrome model

[0082] One hundred Wistar rats were randomly divided into a blank group, a model group, a positive drug group (Zhuanggu Guanjie Pills, China Resources Sanjiu Medical & Pharmaceutical Co., Ltd.; Approval No. Z44023377), a high-dose group and a low-dose group of Example 1 of the present invention, a total of 5 groups, with 20 rats in each group. Except for the blank group, on the first day of modeling, 0.1 mL of Freund's complete adjuvant was injected into the left hind paw subcutaneous tissue of each rat once. After 7 days of modeling, 0.1 mL was injected again for booster immunization to establish a model of adjuvant arthritis rats. The rats were placed in hot water at 36-38 °C with a water depth of 2 cm, accompanied by a wind force of 3 gears, and at the same time given a constant temperature steam fumigation with a 37 °C water bath, once a day for 20 minutes each time, for 14 consecutive days. Since the 15th day of modeling, the rats in each administration group were given gavage administration, and the blank group and the model group were given an equal amount of normal saline by gavage, once a day for 21 consecutive days.

[0083] Measurement of foot swelling degree: The plantar volume of the inflamed foot of each group of rats was measured after the last administration on the 35th day. The results are shown in Table 4.

[0084] Table 4 Effect of the granule of the present invention on the foot swelling degree of rats (x±s)

[0085]

[0086]

[0087] Compared with the blank group, ## P < 0.01, compared with the model group * P < 0.05, ** P < 0.01

[0088] As shown in the results of Table 4, compared with the blank group, the plantar volume of the model group was significantly increased after inflammation induction (P < 0.01), indicating that the model was successfully established; compared with the model, the high-dose group and low-dose group of Example 1 of the present invention could reduce the plantar volume in rats with wind-heat arthralgia syndrome (P < 0.05), and the effect of the high-dose group was close to that of the positive drug group.

[0089] Levels of TNF-α and IL-1β in rat serum: At 1 h after the last administration on the 35th day, blood was collected from the abdominal aorta, allowed to stand for 30 min, and then centrifuged at 3000 r / min for 10 min to separate the serum. The levels of TNF-α and IL-1β in rat serum were measured using a kit, and the specific operation was carried out according to the instructions of the kit. The results are shown in Table 5.

[0090] Table 5 Effects of the granule of the present invention on the levels of TNF-α and IL-1β in rats (x±s)

[0091] Group TNF-α (ng / L) IL-1B (ng / L) Blank group 165.764±34.768 19.387±5.246 Model group <![CDATA[272.513±63.561 ## > <![CDATA[34.657±6.275 ## > Positive drug group <![CDATA[174.636±32.425 ** > <![CDATA[25.737±5.428 * > Low dose group <![CDATA[235.872±38.518 * > <![CDATA[24.379±5.497 * > High dose group <![CDATA[170.714±36.906 ** > <![CDATA[18.671±5.742 ** >

[0092] ## P < 0.01, compared with the model group * P < 0.05, ** P < 0.01

[0093] As shown in the results of Table 5, compared with the blank group, the levels of TNF-α and IL-1β in the model group were significantly increased (P < 0.01), indicating that the model was successfully established. Compared with the model group, the positive drug group, the low-dose and high-dose groups of Example 1 of the present invention all significantly reduced the levels of TNF-α and IL-1β in rats with wind-heat arthralgia syndrome, indicating that the present invention has an obvious anti-inflammatory effect.

[0094] Example 6: Clinical study

[0095] A total of 100 patients with chronic knee pain in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from September 2021 to October 2023 were randomly divided into a control group and an Example 1 group. In the control group, there were 28 males and 22 females; the age was 52 - 79 years old, with an average age of 58.6 years. In the Example 1 group, there were 24 males and 26 females, aged 53 - 78 years old, with an average age of 59.9 years.

[0096] Diagnostic Criteria: Western Medicine Diagnostic Criteria: Chronic knee pain caused by osteoarthritis, synovitis, meniscus injury, ligament injury, gouty arthritis, and infectious arthritis. Comprehensive judgment is made by combining magnetic resonance imaging, X-ray films, enhanced scans, etc. The general onset time is more than three years.

[0097] Traditional Chinese Medicine Diagnostic Criteria: Clinical manifestations are as follows: pain in the limb joints, with redness, heat, and severe swelling and pain at the pain site, muscle spasms, and the hand cannot get close, making it even more difficult to get out of bed. The pain is worse at night than during the day. Patients often have symptoms such as fever, thirst, restlessness, and preference for cold over heat. The tongue is red, the tongue coating is yellow and dry, and the pulse is slippery and rapid.

[0098] Medication Administration Method: Example 1 Group: Use the granule prepared in Example 1. The daily dosage is: Salvia miltiorrhiza 25g, Ligusticum chuanxiong 20g, Carthamus tinctorius 15g, Pinellia ternata 10g, Citrus reticulata 20g, Peucedanum praeruptorum 20g, Phellodendron amurense 15g, Gardenia jasminoides 25g, Polygonum cuspidatum 20g, Astragalus membranaceus 25g, Atractylodes macrocephala 20g, Alisma orientale 10g, Plantago asiatica 20g, Eucommia ulmoides 10g, Cuscuta chinensis 20g, Rehmannia glutinosa 15g, Lycopodium clavatum 15g, Coix lacryma-jobi 20g, Magnolia officinalis 15g, Bupleurum chinense 15g, Aurantii Fructus Immaturus 10g, Achyranthes bidentata 15g, Spatholobus suberectus 20g. Take it in two doses for 4 consecutive weeks; the control group takes Zhuanggu Guanjie Pills (China Resources Sanjiu Medical & Pharmaceutical Co., Ltd.; Approval Number: Z44023377), 6 grams each time, twice a day, for 4 consecutive weeks.

[0099] Observation Indicators: Record the main clinical symptom scores of patients before treatment and 15 days after treatment. The Lysholm knee joint scoring standard is used to evaluate the knee joint function. The traditional Chinese medicine syndrome scoring standard is formulated with reference to the efficacy and quantification criteria in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" in 2002: 4 main symptoms (pain in the limb joints, redness, heat, and severe swelling and pain at the pain site, muscle spasms) and 3 secondary symptoms (the hand cannot get close, making it even more difficult to get out of bed, the pain is worse at night than during the day). A semi-quantitative grading scoring evaluation method is used, that is, according to the 4 grades of none, mild, moderate, and severe, the main symptoms are scored as 0, 2, 4, 6 points, and the secondary symptoms are scored as 0, 1, 2, 3 points. The tongue and pulse are described specifically and not scored.

[0100] Efficacy Criteria: Recovery: The traditional Chinese medicine signs and symptoms disappear, and the total syndrome score is reduced by ≥95% compared with before treatment; Marked Effect: The traditional Chinese medicine signs and symptoms are significantly improved, and the total syndrome score is reduced by ≥70% and <95% compared with before treatment; Effective: The traditional Chinese medicine signs and symptoms have improved, and the total syndrome score is reduced by ≥30% and <70% compared with before treatment; Ineffective: The traditional Chinese medicine signs and symptoms have not improved significantly or have even worsened, and the total syndrome score is reduced by <30% compared with before treatment. The results are shown in Table 6.

[0101] Table 6 Efficacy Observation

[0102] Group Cured Markedly effective Effective Ineffective Effective rate (%) Control group 13 12 16 9 82 Group of the present invention 25 17 5 3 94

[0103] As can be seen from the results in Table 6, in the control group, 13 cases were cured, 12 cases showed marked improvement, 16 cases were effective, 9 cases were ineffective, and the effective rate was 82%. In the group of the present invention, 25 cases were cured, 17 cases showed marked improvement, 5 cases were effective, 3 cases were ineffective, and the effective rate was 94%. The effect of Example 1 of the present invention is significantly better than that of the control group, indicating that the compatibility of the present invention is reasonable and can treat chronic knee pain of the heat arthralgia syndrome type.

[0104] Although the embodiments of the present invention have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine granule for treating chronic knee pain, characterized in that, By weight parts, the raw materials of the traditional Chinese medicine granule are composed of the following components: 20 - 30 parts of Salvia miltiorrhiza, 15 - 25 parts of Ligusticum chuanxiong, 10 - 20 parts of Carthamus tinctorius, 8 - 12 parts of Pinellia ternata, 15 - 25 parts of Citrus reticulata Blanco, 15 - 25 parts of Peucedanum praeruptorum Dunn, 12 - 18 parts of Phellodendron amurense Rupr., 20 - 30 parts of Gardenia jasminoides Ellis, 15 - 25 parts of Polygonum cuspidatum Sieb. et Zucc., 20 - 30 parts of Astragalus membranaceus (Fisch.) Bunge, 15 - 25 parts of Atractylodes macrocephala Koidz., 8 - 12 parts of Alisma orientale (Sam.) Juz., 15 - 25 parts of Plantago asiatica L., 8 - 12 parts of Eucommia ulmoides Oliv., 15 - 25 parts of Cuscuta chinensis Lam., 10 - 20 parts of Rehmannia glutinosa Libosch. f. hueichingensis (Chao) Hsiao & Keng, 12 - 18 parts of Lycopodium clavatum L., 15 - 25 parts of Coix lacryma-jobi L., 10 - 20 parts of Magnolia officinalis Rehd. et Wils., 10 - 20 parts of Bupleurum chinense DC., 8 - 12 parts of Aurantii Fructus Immaturus, 10 - 20 parts of Achyranthes bidentata Blume, 15 - 25 parts of Spatholobus suberectus Dunn.

2. The traditional Chinese medicine granule for treating chronic knee joint pain according to claim 1, wherein By weight parts, the raw materials of the traditional Chinese medicine granule are composed of the following components: 25 parts of Salvia miltiorrhiza, 20 parts of Ligusticum chuanxiong, 15 parts of Carthamus tinctorius, 10 parts of Pinellia ternata, 20 parts of Citrus reticulata Blanco, 20 parts of Peucedanum praeruptorum Dunn, 15 parts of Phellodendron amurense Rupr., 25 parts of Gardenia jasminoides Ellis, 20 parts of Polygonum cuspidatum Sieb. et Zucc., 25 parts of Astragalus membranaceus (Fisch.) Bunge, 20 parts of Atractylodes macrocephala Koidz., 10 parts of Alisma orientale (Sam.) Juz., 20 parts of Plantago asiatica L., 10 parts of Eucommia ulmoides Oliv., 20 parts of Cuscuta chinensis Lam., 15 parts of Rehmannia glutinosa Libosch. f. hueichingensis (Chao) Hsiao & Keng, 15 parts of Lycopodium clavatum L., 20 parts of Coix lacryma-jobi L., 15 parts of Magnolia officinalis Rehd. et Wils., 15 parts of Bupleurum chinense DC., 10 parts of Aurantii Fructus Immaturus, 15 parts of Achyranthes bidentata Blume, 20 parts of Spatholobus suberectus Dunn.

3. The traditional Chinese medicine granule for treating chronic knee joint pain according to claim 1, wherein, The preparation method includes the following steps; (1) Take Salvia miltiorrhiza, Ligusticum chuanxiong, Carthamus tinctorius, Citrus reticulata Blanco, and Aurantii Fructus Immaturus, and extract volatile oil by supercritical carbon dioxide extraction; (2) Combine the medicinal residues after extracting volatile oil in step (1) with other traditional Chinese medicine raw materials, soak with 2 times of water for 1 h, add 10 times the amount of water, decoct twice, each time for 1 - 3 h, filter, combine the filtrates, concentrate to an extract with a relative density of 1.15 - 1.25 at 80 °C, dry in an environment of 60 °C and 0.07 - 0.08 Mpa, and pulverize into fine powder for standby after drying; (3) Take the fine powder prepared in step (2), spray the volatile oil prepared in step (1), and add excipients to prepare granules.

4. The traditional Chinese medicine granule for treating chronic knee joint pain according to claim 3, wherein, In step (1) of the preparation method, the conditions for supercritical carbon dioxide extraction are: extraction pressure is 25 - 35 MPa, extraction temperature is 70 - 75 °C, separation column pressure is 22 - 25 MPa, temperature is 30 - 50 °C, separation kettle pressure is 6 - 10 MPa, temperature is 30 - 40 °C, and extraction and separation time is 2 - 4 hours.

5. The traditional Chinese medicine granule for treating chronic knee joint pain according to claim 4, wherein, In step (1) of the preparation method, the conditions for supercritical carbon dioxide extraction are: extraction pressure is 30 MPa, extraction temperature is 72 °C, separation column pressure is 24 MPa, temperature is 40 °C, separation kettle pressure is 8 MPa, temperature is 35 °C, and extraction and separation time is 3 hours.

6. The traditional Chinese medicine granule for treating chronic knee joint pain according to claim 3, wherein, The excipients in step (1) of the preparation method are lactose, hydroxypropyl methylcellulose, and polyvinylpyrrolidone. In step (3), the weight ratio of the total weight of the fine powder and the volatile oil to lactose, hydroxypropyl methylcellulose, and polyvinylpyrrolidone is 100:10:20:10, and polyvinylpyrrolidone is used as a binder and dissolved with an appropriate amount of water.

7. Use of the traditional Chinese medicine granule for treating chronic knee pain as described in claim 1 in the preparation of a drug for treating chronic knee pain.

8. Use of the traditional Chinese medicine granule for treating chronic knee pain according to claim 1 in the preparation of a medicament for treating chronic knee pain, characterized in that, Chronic knee pain belongs to the type of heat arthralgia syndrome.

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