Traditional Chinese medicine preparation for treating bilateral knee joint osteoarthropathy and preparation method thereof

Abstract

The invention provides a traditional Chinese medicine preparation for treating bilateral knee joint osteoarthropathy, which is prepared by extracting the following traditional Chinese medicines in parts by weight: 15-25 parts of rhizoma acori graminei, 20-30 parts of polygala tenuifolia, 18-22 parts of prepared rehmannia root, 15-25 parts of dogwood, 10-20 parts of glossy privet fruit, 15-25 parts of semen cuscutae, 8-12 parts of coptis chinensis and the like. The traditional Chinese medicine composition has the effects of inducing resuscitation and eliminating phlegm, inducing resuscitation and benefiting intelligence, enriching blood and nourishing yin, nourishing liver and kidney, discharging heart fire, promoting kidney water to be used as heart, promoting blood circulation, nourishing blood and harmonizing blood, invigorating spleen and replenishing qi, and lifting qi of liver and spleen, and can be used for jointly treating bilateral knee joint osteoarthropathy caused by deficiency of liver and kidney. The traditional Chinese medicine preparation and granules prepared by the invention are excellent in dissolubility, relatively good in flowability, remarkable in curative effect, non-toxic, simple and convenient to use, easy to accept by patients and suitable for popularization.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine preparation for treating bilateral knee osteoarthritis and its preparation method. Background Technology

[0002] Bilateral knee osteoarthritis is a disease caused by degeneration and damage to the articular cartilage, and reactive hyperplasia of the joint margins and subchondral bone. It mainly includes knee pain, joint deformity (usually varus deformity, rarely valgus deformity), joint swelling, and limited joint movement. Early treatment may involve oral medications, such as cartilage-nourishing drugs (glucosamine hydrochloride, glucosamine sulfate, etc.) and anti-inflammatory and analgesic drugs (meloxicam, celecoxib, etc.). Intra-articular injections, such as sodium hyaluronate, can also be administered. In later stages, if joint pain is significant, joint replacement surgery may be necessary. Non-pharmacological treatments, such as self-training, weight loss, and range of motion exercises, can also help protect the joint. Surgical treatment is inherently invasive, causing pain and increasing the risk of complications such as infection, vascular and nerve damage, skin and bone necrosis, patellar hypoplasia, and limited joint movement. Patients may experience gastrointestinal discomfort, such as abdominal pain, diarrhea, and nausea, after taking chemotherapy drugs. Traditional Chinese medicine has advantages such as few side effects and definite curative effect in treating bilateral knee osteoarthritis, therefore there is a need to provide a traditional Chinese medicine composition. Summary of the Invention

[0003] Therefore, this invention proposes a traditional Chinese medicine preparation for treating bilateral knee osteoarthritis and its preparation method, and solves the problems of poor granulation effect and the need to improve the efficacy of the prepared granules in the existing technology.

[0004] One aspect of the present invention provides a traditional Chinese medicine preparation for treating bilateral knee osteoarthritis, which is prepared by extracting and preparing the following traditional Chinese medicines in parts by weight: 15-25 parts of Acorus tatarinowii, 20-30 parts of Polygala tenuifolia, 18-22 parts of Rehmannia glutinosa, 15-25 parts of Cornus officinalis, 10-20 parts of Ligustrum lucidum, 15-25 parts of Cuscuta chinensis, 8-12 parts of Coptis chinensis, 20-30 parts of Nelumbo nucifera seed heart, 15-25 parts of Gardenia jasminoides, 10-20 parts of Lophatherum gracile, 15-25 parts of Angelica sinensis, 10-20 parts of Curcuma longa, 20-30 parts of Paeonia lactiflora, 15-25 parts of Codonopsis pilosula, 20-30 parts of Poria cocos, and 15-25 parts of Atractylodes macrocephala.

[0005] The traditional Chinese medicine preparation for treating bilateral knee osteoarthritis is prepared from the following parts by weight of traditional Chinese medicine: 20 parts of Acorus tatarinowii, 25 parts of Polygala tenuifolia, 20 parts of Rehmannia glutinosa, 20 parts of Cornus officinalis, 15 parts of Ligustrum lucidum, 20 parts of Cuscuta chinensis, 10 parts of Coptis chinensis, 25 parts of Nelumbo nucifera seed heart, 20 parts of Gardenia jasminoides, 15 parts of Lophatherum gracile, 20 parts of Angelica sinensis, 15 parts of Curcuma longa, 25 parts of Paeonia lactiflora, 20 parts of Codonopsis pilosula, 25 parts of Poria cocos, and 20 parts of Atractylodes macrocephala.

[0006] The traditional Chinese medicine preparation for treating bilateral knee osteoarthritis is prepared by the following steps:

[0007] (1) Take the following medicinal materials: Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. Wash the above sixteen ingredients. Extract the volatile oil from Acorus tatarinowii, Angelica sinensis, and Curcuma longa by steam distillation. Encapsulate the volatile oil with cyclodextrin to obtain inclusion complexes. Add water to the remaining thirteen ingredients and decoct twice, the first time for 3 hours and the second time for 2 hours. Add the following ingredients during the second decoction: The residues of Acorus tatarinowii, Angelica sinensis, and Curcuma longa after the extraction of volatile oil were combined with the decoctions from the two decoctions. The extracts from the steam distillation process of Acorus tatarinowii, Angelica sinensis, and Curcuma longa were added and filtered. The filtrate was allowed to stand and settle. The supernatant was concentrated to a concentration with a relative density of 1.10 measured at 85°C. The concentrate was allowed to stand for 8 hours. The supernatant was then filtered and concentrated to an extract with a relative density of 1.20 measured at 85°C. The extract was then spray-dried to obtain a powder.

[0008] (2) The spray-dried powder and the volatile oil cyclodextrin prepared in step (1) are mixed together, and excipients are added to granulate the mixture to prepare granules.

[0009] The traditional Chinese medicine preparation for treating bilateral knee osteoarthritis is prepared by spray drying the extract in step (1). The inlet air temperature of the spray drying is 140-160℃, the feed flow rate is 12-16r / min, and the atomization pressure is 0.2Mpa, so as to obtain extract powder with a water content of <8%.

[0010] The traditional Chinese medicine preparation for treating bilateral knee osteoarthritis, in step (2) of the preparation method, the excipients are maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose, and the weight ratio of maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose is 1:2:1.

[0011] The application of the traditional Chinese medicine preparation for treating bilateral knee osteoarthritis in the preparation of drugs for treating bilateral knee osteoarthritis.

[0012] All of the above-mentioned Chinese medicinal materials meet the standards of the Chinese Pharmacopoeia.

[0013] In terms of pathogenesis, meridian obstruction, disharmony of qi and blood, stagnation of qi and blood, mutual binding of phlegm and blood stasis, and deficiency of vital energy are the internal conditions for the development of bilateral knee osteoarthritis. Disharmony of ying and wei, deficiency of qi and blood, insufficiency of liver and kidney, and deficiency of spleen and stomach can all lead to deficiency of vital energy and lingering pathogenic factors. The invasion of the body by pathogenic factors such as wind, cold, and dampness, or factors such as strain and trauma, can obstruct the meridians of the knee, resulting in poor circulation of qi and blood, blocked meridians, and pain due to obstruction. Therefore, symptoms such as swelling, pain, heaviness, difficulty in flexion and extension, swelling, and stiffness of the knee joint appear. Traditional Chinese medicine classifies osteoarthritis into syndromes such as wind-cold-dampness obstruction, wind-damp-heat obstruction, deficiency of liver and kidney, and phlegm-blood stasis obstruction. The clinical manifestations of different syndromes are as follows: 1. Wind-cold-dampness syndrome: divided into two types, including cold-predominant pain syndrome, which is characterized by severe pain in the limbs and joints, fixed and immovable, aggravated by cold and relieved by heat. In severe cases, the joints are difficult to flex and extend. The tongue coating is pale white, and the pulse is wiry and tight or deep and slow. Secondly, there is the dampness-induced arthralgia, characterized by heaviness, soreness, and pain in the joints. In severe cases, the joints are swollen and diffuse, heavy and immobile, with limited movement of the limbs. The tongue is pale with a white, greasy coating, and the pulse is soft and slow. 2. Wind-damp-heat arthralgia: Joint pain may involve one or more joints, with limited movement, local burning, redness, and swelling. The pain is unbearable to the touch and is relieved by cold. There may be subcutaneous nodules or erythema, accompanied by fever, sweating, thirst, etc. The tongue is red with a yellow or yellow-greasy coating, and the pulse is slippery and rapid or floating and rapid. 3. Phlegm-blood stasis arthralgia. Symptoms: 1. **Prolonged Bi syndrome:** Muscle and joint pain that is fixed and unmoving, or purplish-dark and swollen skin around the joints, hard to the touch, persistent numbness or heaviness in the limbs, or stiff and deformed joints, difficulty in flexion and extension, with nodules and ecchymosis, dark complexion, purplish-dark tongue, or ecchymosis, white and greasy tongue coating, and wiry and hesitant pulse; 2. **Liver and Kidney Deficiency Syndrome:** Prolonged Bi syndrome with difficulty in flexion and extension of the joints, muscle wasting, soreness and weakness in the lower back and knees; or aversion to cold, cold limbs, five-center heat (palms, soles, and chest), pale red tongue, thin white or scanty tongue coating, and deep, slow or thready and rapid pulse. This disease is common in middle-aged and elderly people, with a high incidence rate. As people age, liver and kidney deficiency occurs, essence and blood decline, causing the tendons and bones to lose nourishment and become unused. This lack of nourishment leads to joint instability, difficulty in flexion and extension, insufficient bone mass, cartilage degeneration, bone hyperplasia, and degenerative changes in the musculoskeletal structure, resulting in knee osteoarthritis. Liver and kidney deficiency syndrome is the most common.

[0014] The *Suwen* (Plain Questions) chapter on the generation of the five viscera states that "the purest essence transforms into marrow, which ascends from the spine into the brain, called brain marrow." The *Lingshu* (Spiritual Pivot) chapter on the sea of ​​marrow states, "The brain is the sea of ​​marrow," and the *Suwen* chapter on strange diseases states, "Marrow is primarily derived from the brain." The *Neijing Jingyi* (Essential Meaning of the Inner Canon) states, "The essence of the kidneys transforms into marrow, which is stored in the brain." These discussions consider the brain to be the sea of ​​marrow, the place where the essence of the body gathers. The brain, as the sea of ​​marrow, includes brain marrow, bone marrow, and spinal cord. The *Nanjing Benyi* (Original Meaning of the Classic of Difficult Issues) states, "Marrow flows from the brain down to the large lobe (BL1), from the large lobe it seeps into the spinal cord, down to the coccyx, and into all the joints." This indicates that brain marrow and bone marrow are interconnected. The *Lingshu* chapter on the differentiation of body fluids in the five types of urinary tract infections records, "Ointment seeps into the bone cavities, nourishing the brain marrow." This points out that the sea of ​​marrow has the function of nourishing bone marrow and brain marrow, ensuring the normal functioning of the body. Furthermore, "The brain is the residence of the primordial spirit, governing the five spirits, regulating the yin and yang of the viscera, and the function of the limbs and bones." The *Jin Nang Mi Lu* (a classic Chinese medical text) also suggests a link between brain dysfunction and mental and physical impairment, with insufficient marrow in the brain contributing to dementia and bone atrophy. This invention utilizes *Acorus tatarinowii* to open the orifices, clear phlegm, refresh the mind, improve intelligence, and resolve dampness and stimulate appetite; and *Polygala tenuifolia* to resolve phlegm, open the orifices, calm the mind, and harmonize the heart and kidneys.

[0015] The *Suwen* (Plain Questions) chapter on flaccid paralysis states: "When the kidney qi is hot... the bones wither and the marrow decreases, resulting in bone flaccidity." The cause of "kidney qi heat" is "exhaustion from long journeys, followed by thirst due to intense heat; thirst causes the yang qi to attack internally, and this internal attack causes heat to accumulate in the kidneys." It also states: "The kidneys are the storehouse of water; now, the water cannot overcome the fire... resulting in bone flaccidity." This invention uses Rehmannia glutinosa (processed) to nourish blood and yin, replenish essence and marrow; Cornus officinalis (processed) to tonify the liver and kidneys, and astringe and consolidate; Ligustrum lucidum (processed) to nourish the liver and kidneys, improve eyesight and darken hair; and Cuscuta chinensis (processed) to tonify the liver and kidneys, consolidate essence and reduce urination. This invention uses Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa (processed), Cornus officinalis, Ligustrum lucidum, and Cuscuta chinensis as the principal herbs.

[0016] Zhang Zihe's *Rumen Shiqin* (Confucian Family Matters) states in its section on "Recent Mysterious Explanations of Wind-Bi-Wei-Jue (A Treatise on Paralysis and Weakness)" that "when kidney water cannot overcome heart fire, heart fire ascends and melts lung metal... then weakness and flaccidity occur." He believes that insufficient kidney yin or weak kidney yang, resulting in kidney water failing to nourish the heart and heart yang becoming excessively hyperactive, is a key pathogenesis of flaccidity. This invention uses Coptis chinensis to clear heat, dry dampness, purge fire, and detoxify; lotus seed heart to clear the heart, calm the mind, harmonize the heart and kidneys, astringe essence, and stop bleeding; gardenia to purge fire, relieve irritability, clear heat, and promote diuresis; and bamboo leaves to clear heat, purge fire, relieve irritability, generate fluids, and promote urination. Coptis chinensis, lotus seed heart, gardenia, and bamboo leaves are used as assistant herbs to purge heart fire, allowing kidney water to nourish the heart and improving the state of liver and kidney deficiency.

[0017] The *Suwen* (Plain Questions) chapter "On the Correspondence of Yin and Yang" states: "The liver stores blood and governs the tendons. The liver is the root of exhaustion; its radiance is in the nails, and its fullness is in the tendons." "The kidneys store essence, govern bones and produce marrow; their radiance is in the hair, and their fullness is in the bones." The liver stores blood, and the kidneys store essence; kidney essence transforms into liver blood. Zhang Lu of the Qing Dynasty, in his *Zhangshi Yitong* (Zhang's Medical Treatise), said: "If qi is not depleted, it returns to the kidneys to become essence; if essence is not leaked, it returns to the liver to transform into pure blood." This means that the liver and kidneys share a common origin, as do essence and blood. Sufficient essence and blood nourish the tendons and bones, resulting in strong tendons and healthy bones. The *Suwen* chapter "On Bi Syndrome" states: "Bi syndrome in the bones causes heaviness; in the vessels causes numbness." The kidneys govern the bones, and the liver governs the tendons. When pathogenic factors invade the tendons and bones, over time, they will inevitably damage the liver and kidneys, depleting qi and blood. Furthermore, the waist is the residence of the kidneys, and the knees are the residence of the tendons. Insufficient liver and kidneys result in weakness and weakness in the waist and knees; depletion of qi and blood leads to palpitations and shortness of breath. The *Suwen* (Plain Questions) chapter "On Reversal and Regulation" states: "When the *ying* (nutritive qi) is deficient, there is numbness; when the *wei* (defensive qi) is deficient, there is no function; when both *ying* and *wei* are deficient, there is both numbness and no function." This condition is a case of deficiency of the body's vital energy and excess of pathogenic factors. Treatment should address both strengthening the body's vital energy and eliminating pathogenic factors, dispelling wind, cold, and dampness while simultaneously tonifying the liver and kidneys' qi and blood. The *Leizheng Sanfa* (Classified Treatments for Diseases) chapter "Bi Syndrome" states: "When the *ying* and *wei* are deficient, the pores are not tightly closed, allowing wind, cold, and dampness to invade internally. The vital energy is obstructed by these pathogenic factors and cannot circulate properly, thus stagnating and causing blood and qi to congeal, eventually leading to *bi*." This indicates that a deficiency of vital energy weakens the body's ability to resist external pathogens, leading to blood and qi stagnation and obstruction of the meridians, eventually resulting in *bi*. The *Lingshu* (Spiritual Pivot) chapter "Meeting of *ying* and *wei*" states: "In the elderly, the qi and blood decline, causing the muscles to wither and the qi channels to become obstructed." Blood stasis forms, the meridians are blocked, and the joints lose nourishment from qi and blood, resulting in "bone *bi*." Therefore, the formula uses Angelica sinensis, Curcuma longa, and Paeonia lactiflora to invigorate, nourish, and harmonize blood; Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala to strengthen the spleen and replenish qi, raising the qi of the liver and spleen. When the qi of the liver and spleen rises, the pain in the lower back and knees will subside. Angelica sinensis, Rehmannia glutinosa, and Paeonia lactiflora are yin-nourishing herbs, which can replenish the yin of the liver and kidneys. When the yin of the liver and kidneys is replenished, the feet will receive blood and one will be able to walk. Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala are qi-boosting herbs, which can nourish the yang of all organs. When the yang of all organs is generated, coldness and numbness will disappear and one will have strength. Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala are used as adjuvant herbs.

[0018] The formula contains Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera seed heart, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. It can open the orifices and resolve phlegm, refresh the mind and improve intelligence, nourish blood and yin, nourish the liver and kidneys, clear heart fire, allow kidney water to nourish the heart, invigorate blood, nourish and harmonize blood, strengthen the spleen and replenish qi, and raise the qi of the liver and spleen. Together, they can treat bilateral knee osteoarthritis of the liver and kidney deficiency type. Detailed Implementation

[0019] To facilitate understanding of the present invention, a more complete description will be given below with reference to various embodiments. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0021] The embodiments of the present invention will be further described below with reference to several examples. The embodiments of the present invention are not limited to the specific embodiments described below. Appropriate modifications can be made within the scope of unchanged main claims.

[0022] Example 1:

[0023] Take 200g of Acorus tatarinowii, 250g of Polygala tenuifolia, 200g of Rehmannia glutinosa (processed), 200g of Cornus officinalis, 150g of Ligustrum lucidum, 200g of Cuscuta chinensis, 100g of Coptis chinensis, 250g of Nelumbo nucifera seed heart, 200g of Gardenia jasminoides, 150g of Lophatherum gracile, 200g of Angelica sinensis, 150g of Curcuma longa, 250g of Paeonia lactiflora, 200g of Codonopsis pilosula, 250g of Poria cocos, and 200g of Atractylodes macrocephala. The preparation method includes the following steps:

[0024] (1) Take the following medicinal materials: Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. Wash the above sixteen herbs. Extract the volatile oil from Acorus tatarinowii, Angelica sinensis, and Curcuma longa by steam distillation. Encapsulate the volatile oil with cyclodextrin to obtain inclusion complexes. Add water to the remaining thirteen herbs and decoct twice, the first time for 3 hours and the second time for 2 hours. Add the residue of Acorus tatarinowii, Angelica sinensis, and Curcuma longa after extracting the volatile oil during the second decoction. Combine the two decoctions. The extract from the steam distillation process of Acorus tatarinowii, Angelica sinensis, and Curcuma longa was added and filtered. The filtrate was allowed to settle, and the supernatant was concentrated to a concentration with a relative density of 1.10 measured at 85℃. The concentrate was allowed to stand for 8 hours, and the supernatant was filtered. The filtrate was concentrated to an extract with a relative density of 1.20 measured at 85℃. The extract was spray-dried to obtain a powder. The inlet air temperature of the spray dryer was 150℃, the feed flow rate was 14 r / min, and the atomization pressure was 0.2 MPa, resulting in an extract powder with a water content of <8%.

[0025] (2) The spray-dried powder and the volatile oil cyclodextrin prepared in step (1) are mixed together to form an inclusion complex. Excipients are added to granulate the mixture. The excipients are maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose. The weight ratio of maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose is 1:2:1. Granules are prepared.

[0026] Example 2:

[0027] Take 150g of Acorus tatarinowii, 300g of Polygala tenuifolia, 180g of Rehmannia glutinosa (processed), 250g of Cornus officinalis, 100g of Ligustrum lucidum, 250g of Cuscuta chinensis, 80g of Coptis chinensis, 300g of Nelumbo nucifera seed heart, 150g of Gardenia jasminoides, 200g of Lophatherum gracile, 150g of Angelica sinensis, 200g of Curcuma longa, 200g of Paeonia lactiflora, 250g of Codonopsis pilosula, 200g of Poria cocos, and 250g of Atractylodes macrocephala. The preparation method includes the following steps:

[0028] (1) Take the following medicinal materials: Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. Wash the above sixteen herbs. Extract the volatile oil from Acorus tatarinowii, Angelica sinensis, and Curcuma longa by steam distillation. Encapsulate the volatile oil with cyclodextrin to obtain inclusion complexes. Add water to the remaining thirteen herbs and decoct twice, the first time for 3 hours and the second time for 2 hours. Add the residue of Acorus tatarinowii, Angelica sinensis, and Curcuma longa after extracting the volatile oil during the second decoction. Combine the two decoctions. The extract from the steam distillation process of Acorus tatarinowii, Angelica sinensis, and Curcuma longa was added and filtered. The filtrate was allowed to settle, and the supernatant was concentrated to a concentration with a relative density of 1.10 measured at 85℃. The concentrate was allowed to stand for 8 hours, and the supernatant was filtered. The filtrate was concentrated to an extract with a relative density of 1.20 measured at 85℃. The extract was spray-dried to obtain a powder. The inlet air temperature of the spray dryer was 140℃, the feed flow rate was 16 r / min, and the atomization pressure was 0.2 MPa, resulting in an extract powder with a water content of <8%.

[0029] (2) The spray-dried powder and the volatile oil cyclodextrin prepared in step (1) are mixed together to form an inclusion complex. Excipients are added to granulate the mixture. The excipients are maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose. The weight ratio of maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose is 1:2:1. Granules are prepared.

[0030] Example 3:

[0031] Take 250g of Acorus tatarinowii, 200g of Polygala tenuifolia, 220g of Rehmannia glutinosa (processed), 150g of Cornus officinalis, 200g of Ligustrum lucidum, 150g of Cuscuta chinensis, 120g of Coptis chinensis, 200g of Nelumbo nucifera seed heart, 250g of Gardenia jasminoides, 100g of Lophatherum gracile, 250g of Angelica sinensis, 100g of Curcuma longa, 300g of Paeonia lactiflora, 150g of Codonopsis pilosula, 300g of Poria cocos, and 150g of Atractylodes macrocephala. The preparation method includes the following steps:

[0032] (1) Take the following medicinal materials: Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. Wash the above sixteen herbs. Extract the volatile oil from Acorus tatarinowii, Angelica sinensis, and Curcuma longa by steam distillation. Encapsulate the volatile oil with cyclodextrin to obtain inclusion complexes. Add water to the remaining thirteen herbs and decoct twice, the first time for 3 hours and the second time for 2 hours. Add the residue of Acorus tatarinowii, Angelica sinensis, and Curcuma longa after extracting the volatile oil during the second decoction. Combine the two decoctions. The extract from the steam distillation process of Acorus tatarinowii, Angelica sinensis, and Curcuma longa was added and filtered. The filtrate was allowed to settle, and the supernatant was concentrated to a concentration with a relative density of 1.10 measured at 85℃. The concentrate was allowed to stand for 8 hours, and the supernatant was filtered. The filtrate was concentrated to an extract with a relative density of 1.20 measured at 85℃. The extract was spray-dried to obtain a powder. The inlet air temperature of the spray dryer was 160℃, the feed flow rate was 12 r / min, and the atomization pressure was 0.2 MPa, resulting in an extract powder with a water content of <8%.

[0033] (2) The spray-dried powder and the volatile oil cyclodextrin prepared in step (1) are mixed together to form an inclusion complex. Excipients are added to granulate the mixture. The excipients are maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose. The weight ratio of maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose is 1:2:1. Granules are prepared.

[0034] Comparative Example 1:

[0035] Take 200g of Acorus tatarinowii, 250g of Polygala tenuifolia, 200g of Rehmannia glutinosa (processed), 200g of Cornus officinalis, 150g of Ligustrum lucidum, 200g of Cuscuta chinensis, 100g of Coptis chinensis, 250g of Nelumbo nucifera seed heart, 200g of Gardenia jasminoides, 150g of Lophatherum gracile, 200g of Angelica sinensis, 150g of Curcuma longa, 250g of Paeonia lactiflora, 200g of Codonopsis pilosula, 250g of Poria cocos, and 200g of Atractylodes macrocephala. The preparation method includes the following steps:

[0036] (1) Take the following medicinal materials: Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. Wash the above sixteen herbs. Extract the volatile oil from Acorus tatarinowii, Angelica sinensis, and Curcuma longa by steam distillation. Encapsulate the volatile oil with cyclodextrin to obtain inclusion complexes. Add water to the remaining thirteen herbs and decoct twice, the first time for 3 hours and the second time for 2 hours. Add the residue of Acorus tatarinowii, Angelica sinensis, and Curcuma longa after extracting the volatile oil during the second decoction. Combine the two decoctions. The extract from the steam distillation process of Acorus tatarinowii, Angelica sinensis, and Curcuma longa was added and filtered. The filtrate was allowed to settle, and the supernatant was concentrated to a concentration with a relative density of 1.10 measured at 85℃. The concentrate was allowed to stand for 8 hours, and the supernatant was filtered. The filtrate was concentrated to an extract with a relative density of 1.20 measured at 85℃. The extract was spray-dried to obtain a powder. The inlet air temperature of the spray dryer was 150℃, the feed flow rate was 14 r / min, and the atomization pressure was 0.2 MPa, resulting in an extract powder with a water content of <8%.

[0037] (2) The spray-dried powder and the volatile oil cyclodextrin prepared in step (1) are mixed to form an inclusion complex. Excipients are added to granulate the mixture. The excipients are maltodextrin and polyethylene glycol PEG 6000. The weight ratio of maltodextrin and polyethylene glycol PEG 6000 is 1:2. Granules are prepared.

[0038] Comparative Example 2:

[0039] Take 200g of Acorus tatarinowii, 250g of Polygala tenuifolia, 200g of Rehmannia glutinosa (processed), 200g of Cornus officinalis, 150g of Ligustrum lucidum, 200g of Cuscuta chinensis, 100g of Coptis chinensis, 250g of Nelumbo nucifera seed heart, 200g of Gardenia jasminoides, 150g of Lophatherum gracile, 200g of Angelica sinensis, 150g of Curcuma longa, 250g of Paeonia lactiflora, 200g of Codonopsis pilosula, 250g of Poria cocos, and 200g of Atractylodes macrocephala. The preparation method includes the following steps:

[0040] (1) Take the following medicinal materials: Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. Wash the above sixteen herbs. Extract the volatile oil from Acorus tatarinowii, Angelica sinensis, and Curcuma longa by steam distillation. Encapsulate the volatile oil with cyclodextrin to obtain inclusion complexes. Add water to the remaining thirteen herbs and decoct twice, the first time for 3 hours and the second time for 2 hours. Add the residue of Acorus tatarinowii, Angelica sinensis, and Curcuma longa after extracting the volatile oil during the second decoction. Combine the two decoctions. The extract from the steam distillation process of Acorus tatarinowii, Angelica sinensis, and Curcuma longa was added and filtered. The filtrate was allowed to settle, and the supernatant was concentrated to a concentration with a relative density of 1.10 measured at 85℃. The concentrate was allowed to stand for 8 hours, and the supernatant was filtered. The filtrate was concentrated to an extract with a relative density of 1.20 measured at 85℃. The extract was spray-dried to obtain a powder. The inlet air temperature of the spray dryer was 150℃, the feed flow rate was 14 r / min, and the atomization pressure was 0.2 MPa, resulting in an extract powder with a water content of <8%.

[0041] (2) The spray-dried powder and the volatile oil cyclodextrin prepared in step (1) are mixed together to form an inclusion complex. Excipients are added to granulate the mixture. The excipients are maltodextrin and microcrystalline cellulose, with a weight ratio of 1:1 between maltodextrin and microcrystalline cellulose. Granules are prepared.

[0042] Comparative Example 3:

[0043] Take 200g of Acorus tatarinowii, 250g of Polygala tenuifolia, 200g of Rehmannia glutinosa (processed), 200g of Cornus officinalis, 150g of Ligustrum lucidum, 200g of Cuscuta chinensis, 100g of Coptis chinensis, 250g of Nelumbo nucifera seed heart, 200g of Gardenia jasminoides, 150g of Lophatherum gracile, 200g of Angelica sinensis, 150g of Curcuma longa, 250g of Paeonia lactiflora, 200g of Codonopsis pilosula, 250g of Poria cocos, and 200g of Atractylodes macrocephala. The preparation method includes the following steps:

[0044] (1) Take the following medicinal materials: Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. Wash the above sixteen herbs. Extract the volatile oil from Acorus tatarinowii, Angelica sinensis, and Curcuma longa by steam distillation. Encapsulate the volatile oil with cyclodextrin to obtain inclusion complexes. Add water to the remaining thirteen herbs and decoct twice, the first time for 3 hours and the second time for 2 hours. Add the residue of Acorus tatarinowii, Angelica sinensis, and Curcuma longa after extracting the volatile oil during the second decoction. Combine the two decoctions. The extract from the steam distillation process of Acorus tatarinowii, Angelica sinensis, and Curcuma longa was added and filtered. The filtrate was allowed to settle, and the supernatant was concentrated to a concentration with a relative density of 1.10 measured at 85℃. The concentrate was allowed to stand for 8 hours, and the supernatant was filtered. The filtrate was concentrated to an extract with a relative density of 1.20 measured at 85℃. The extract was spray-dried to obtain a powder. The inlet air temperature of the spray dryer was 150℃, the feed flow rate was 14 r / min, and the atomization pressure was 0.2 MPa, resulting in an extract powder with a water content of <8%.

[0045] (2) The spray-dried powder and the volatile oil cyclodextrin prepared in step (1) are mixed to form an inclusion complex. Excipients are added to granulate the mixture. The excipients are polyethylene glycol PEG 6000 and microcrystalline cellulose. The weight ratio of polyethylene glycol PEG 6000 and microcrystalline cellulose is 2:1. Granules are prepared.

[0046] Example 4: Pharmacodynamic Study

[0047] Experimental animals: 80 healthy SD rats were selected and after an adaptation feeding week, 60 rats were randomly selected and divided into four groups: normal group, model group, positive control drug diclofenac sodium sustained-release capsule group (National Drug Approval Number H20066213, Nanjing Yiheng Pharmaceutical Co., Ltd., production batch number: 20230209), and granule group of Example 1 of this invention, with 15 rats in each group.

[0048] Modeling method: All rats except the normal group were modeled. A knee osteoarthritis model was established by intra-articular injection of papain into the knee joint cavity of rats. The specific procedure was as follows: Rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3 ml / 100g). The hair around the right knee joint was shaved, and the skin was disinfected with 75% ethanol. The right knee joint was gently bent, and a needle was inserted approximately 0.5 cm above and outside the patellar ligament attachment point. 0.2 ml of 4% papain solution was injected into the right knee joint cavity of the rat. This was repeated every 3 days for a total of 3 injections.

[0049] Administration method: The dosage was calculated according to the conversion formula between adult and experimental animal dosages. The dosage of diclofenac sodium sustained-release capsules was 0.01 g / kg, and the dosage of granules in Example 1 of this invention was 10 g / kg. The normal group and the model group were given the corresponding dose of physiological saline once a day. The samples were collected after 4 weeks.

[0050] Experimental procedure: Blood was collected from the femoral artery to separate serum and synovial fluid. The levels of MMP-3 and TNF-α in the serum and synovial fluid were detected by ELISA. The results are shown in Table 1.

[0051] Table 1. Comparison of MMP-3 and TNF-α levels in serum and synovial fluid.

[0052]

[0053] Compared with the normal group: * P<0.05, ** P < 0.01; Compared with the model group: # P<0.05, ## P<0.01.

[0054] Table 1 shows that the levels of MMP-3 and TNF-α in serum and synovial fluid significantly increased after modeling, indicating successful modeling. After using the positive control drug and the granules of Example 1 of this invention, the levels of MMP-3 and TNF-α in serum and synovial fluid significantly decreased. In patients with knee osteoarthritis, the level of MMP-3 in serum and synovial fluid gradually increased with disease progression (early, middle, and late stages), reaching its highest value in the late stage. As a pro-inflammatory factor, TNF-α significantly increased in the early stages of knee osteoarthritis and continued to rise with disease severity. The levels of TNF-α in the serum and synovial fluid of patients were significantly higher than those of healthy individuals, with the highest levels in late-stage patients. This invention can reduce the levels of MMP-3 and TNF-α in serum and synovial fluid, indicating that it can reduce the levels of inflammatory factors in patients with knee osteoarthritis, improve the symptoms of osteoarthritis, and treat osteoarthritis, with better efficacy than the positive control drug.

[0055] Example 5: Record of hot water dissolution of granules and angle of repose

[0056] The hot water solubility and particle repose angle of Examples 1-3 and Comparative Examples 1-3 were measured, and the results are shown in Table 2.

[0057] Table 2. Records of hot water dissolution of granules and angle of repose.

[0058]

[0059] As shown in Table 2, the granules prepared in Examples 1-3 of this application exhibit excellent solubility. The angle of repose test results show that the granules prepared in this application have better flowability than those in Comparative Examples 1-3. This indicates that the excipients are maltodextrin, polyethylene glycol PEG 6000, and microcrystalline cellulose, and that the formulation is reasonable when the weight ratio of maltodextrin, polyethylene glycol PEG 6000, and microcrystalline cellulose is 1:2:1, which helps to improve the product quality of the granules.

[0060] Example 6: Clinical Study

[0061] Case selection: 100 patients with bilateral knee osteoarthritis who visited the outpatient department of Suzhou Integrated Traditional Chinese and Western Medicine Hospital from May 2023 to December 2024 were randomly divided into two groups: the treatment group (Example 1 of this invention) and the positive control drug diclofenac sodium sustained-release capsule group (National Drug Approval Number H20066213, Nanjing Yiheng Pharmaceutical Co., Ltd., production batch number: 20230209), with 50 patients in each group. In the treatment group, there were 28 males and 22 females; the mean age was 65.4 years; the mean disease duration was 12.5 years. In the positive control drug group, there were 26 males and 24 females; the mean age was 64.8 years; the mean disease duration was 11.8 years. There was no significant difference between the two groups.

[0062] Diagnostic criteria: According to the American College of Rheumatology's 1995 diagnostic criteria for knee osteoarthritis, the following criteria must be met: ① Knee pain for most of the past month; ② X-ray showing osteophyte formation; ③ Joint fluid examination consistent with osteoarthritis; ④ Age ≥ 40 years; ⑤ Morning stiffness ≤ 30 minutes; ⑥ Bone crepitus. Patients meeting criteria 1+2, 1+3+5+6, or 1+4+5+6 can be diagnosed with knee osteoarthritis. Patients with bilateral knee osteoarthritis diagnosed by Traditional Chinese Medicine as having liver and kidney deficiency syndrome have the following specific symptoms: chronic arthralgia, difficulty in joint flexion and extension, muscle wasting, lower back and knee weakness; or aversion to cold, cold limbs, five-center heat (palms, soles, and chest), pale red tongue, thin white or scanty coating, and deep, slow or thready, rapid pulse.

[0063] Administration method: The treatment group was given the granules prepared in Example 1 (daily dosage: Acorus tatarinowii 20g, Polygala tenuifolia 25g, Rehmannia glutinosa 20g, Cornus officinalis 20g, Ligustrum lucidum 15g, Cuscuta chinensis 20g, Coptis chinensis 10g, Nelumbo nucifera seed heart 25g, Gardenia jasminoides 20g, Lophatherum gracile 15g, Angelica sinensis 20g, Curcuma longa 15g, Paeonia lactiflora 25g, Codonopsis pilosula 20g, Poria cocos 25g, Atractylodes macrocephala 20g), orally, three times a day, for one month. The positive control group was given diclofenac sodium sustained-release capsules (National Drug Approval Number H20066213, Nanjing Yiheng Pharmaceutical Co., Ltd., production batch number: 20230209), 50mg (1 capsule) twice a day, for one month.

[0064] Efficacy criteria: Joint pain was assessed using the Visual Analogue Scale (VAS), and joint swelling was assessed by observation (visualizing the knee joint) and palpation (pressing the knee joint). Knee joint range of motion was assessed using the Lysholm scoring system. Based on the degree of improvement in clinical symptoms and signs, the following criteria were used: clinical remission was defined as: disappearance of knee pain and swelling, and improvement in joint range of motion >80%; effective was defined as: partial improvement of knee pain, partial disappearance of swelling, and improvement in joint range of motion 25%-50%; and ineffective was defined as: no significant improvement of knee pain and swelling, and improvement in joint range of motion <25%.

[0065] Results: See Table 3.

[0066] Table 3 Clinical efficacy

[0067]

[0068] As shown in Table 3, in the treatment group, 31 cases achieved clinical remission, 15 cases achieved effectiveness, and 4 cases achieved no effect, with a total effective rate of 92%; in the positive drug group, 22 cases achieved clinical remission, 21 cases achieved effectiveness, and 7 cases achieved no effect, with a total effective rate of 86%. This indicates that the present invention has a good therapeutic effect on patients with bilateral knee osteoarthritis of the liver and kidney deficiency syndrome, and the effect is better than that of the positive drug group.

[0069] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine preparation for treating bilateral knee osteoarthritis, characterized in that, It is prepared from the following Chinese medicinal herbs in parts by weight: Acorus tatarinowii 15-25 parts, Polygala tenuifolia 20-30 parts, Rehmannia glutinosa 18-22 parts, Cornus officinalis 15-25 parts, Ligustrum lucidum 10-20 parts, Cuscuta chinensis 15-25 parts, Coptis chinensis 8-12 parts, Nelumbo nucifera seed heart 20-30 parts, Gardenia jasminoides 15-25 parts, Lophatherum gracile 10-20 parts, Angelica sinensis 15-25 parts, Curcuma longa 10-20 parts, Paeonia lactiflora 20-30 parts, Codonopsis pilosula 15-25 parts, Poria cocos 20-30 parts, Atractylodes macrocephala 15-25 parts.

2. The traditional Chinese medicine preparation for treating bilateral knee osteoarthritis according to claim 1, characterized in that, It is prepared from the following Chinese medicinal herbs in parts by weight: 20 parts of Acorus tatarinowii, 25 parts of Polygala tenuifolia, 20 parts of Rehmannia glutinosa, 20 parts of Cornus officinalis, 15 parts of Ligustrum lucidum, 20 parts of Cuscuta chinensis, 10 parts of Coptis chinensis, 25 parts of Nelumbo nucifera seed heart, 20 parts of Gardenia jasminoides, 15 parts of Lophatherum gracile, 20 parts of Angelica sinensis, 15 parts of Curcuma longa, 25 parts of Paeonia lactiflora, 20 parts of Codonopsis pilosula, 25 parts of Poria cocos, and 20 parts of Atractylodes macrocephala.

3. The traditional Chinese medicine preparation for treating bilateral knee osteoarthritis according to claim 1, characterized in that, The preparation method includes the following steps: (1) Take the following medicinal materials: Acorus tatarinowii, Polygala tenuifolia, Rehmannia glutinosa, Cornus officinalis, Ligustrum lucidum, Cuscuta chinensis, Coptis chinensis, Nelumbo nucifera, Gardenia jasminoides, Lophatherum gracile, Angelica sinensis, Curcuma longa, Paeonia lactiflora, Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala. Wash the above sixteen ingredients. Extract the volatile oil from Acorus tatarinowii, Angelica sinensis, and Curcuma longa by steam distillation. Encapsulate the volatile oil with cyclodextrin to obtain inclusion complexes. Add water to the remaining thirteen ingredients and decoct twice, the first time for 3 hours and the second time for 2 hours. Add the following ingredients during the second decoction: The residues of Acorus tatarinowii, Angelica sinensis, and Curcuma longa after the extraction of volatile oil were combined with the decoctions from the two decoctions. The extracts from the steam distillation process of Acorus tatarinowii, Angelica sinensis, and Curcuma longa were added and filtered. The filtrate was allowed to stand and settle. The supernatant was concentrated to a concentration with a relative density of 1.10 measured at 85°C. The concentrate was allowed to stand for 8 hours. The supernatant was then filtered and concentrated to an extract with a relative density of 1.20 measured at 85°C. The extract was then spray-dried to obtain a powder. (2) The spray-dried powder and the volatile oil cyclodextrin prepared in step (1) are mixed together and excipients are added to granulate the mixture to prepare granules.

4. The traditional Chinese medicine preparation for treating bilateral knee osteoarthritis according to claim 3, characterized in that, In step (1) of the preparation method, the extract is spray-dried. The inlet air temperature of the spray drying is 140-160℃, the feed flow rate is 12-16r / min, and the atomization pressure is 0.2Mpa, so as to obtain extract powder with a water content of <8%.

5. The traditional Chinese medicine preparation for treating bilateral knee osteoarthritis according to claim 3, characterized in that, In step (2) of the preparation method, the excipients are maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose, and the weight ratio of maltodextrin, polyethylene glycol PEG 6000 and microcrystalline cellulose is 1:2:

1.

6. The application of the traditional Chinese medicine preparation for treating bilateral knee osteoarthritis according to claim 1 in the preparation of drugs for treating bilateral knee osteoarthritis.

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