Traditional Chinese medicine composition for treating femoral head necrosis, traditional Chinese medicine preparation and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating femoral head necrosis, a traditional Chinese medicine preparation and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines. Aiming at the problems of western medicine and traditional Chinese medicine treatment for femoral head necrosis at present, the traditional Chinese medicine composition comprises the following traditional Chinese medicine components by weight: 15g of salvia miltiorrhiza, 10g of ligusticum wallichii, 10g of angelica sinensis, 12g of red paeony root, 6g of ground beetle, 3g of leech, 7g of rhizoma sparganii, 7g of curcuma zedoary, 10g of epimedium, 10g of dipsacus root, 4g of cinnamon and 6g of liquorice, after each traditional Chinese medicine component is weighed and soaked, the traditional Chinese medicine components are respectively decocted twice, mixed, filtered, concentrated and bagged. The traditional Chinese medicine composition disclosed by the invention is unique in formula, is used for tonifying liver and kidney, promoting blood circulation to remove meridian obstruction, improving femoral head blood circulation and promoting femoral head necrosis repair, is remarkable in curative effect and small in side effect, and can be used for hip protection treatment of patients suffering from femoral head necrosis in early and middle periods and treatment of patients who are unwilling to accept hip replacement surgery in late periods.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition and a traditional Chinese medicine preparation for treating femoral head necrosis and a preparation method thereof. Background Art

[0002] Avascular necrosis of the femoral head is a pathological process caused by the destruction of blood supply to the femoral head or degeneration of bone cells due to different reasons, leading to the death of the active components of the bone (osteocytes, bone marrow hematopoietic cells and fat cells). It is a difficult disease in clinical practice. Avascular necrosis of the femoral head is characterized by subchondral bone microfractures and subsequent collapse of the femoral head, which eventually leads to hip osteoarthritis. It is a disabling disease with clinical manifestations such as hip pain, limited joint function, and lower limb muscle atrophy. It is more common in young and middle-aged people, with a long course of disease and a high disability rate. In the late stage of the disease, hip replacement surgery is eventually required.

[0003] There are many causes of femoral head necrosis, which can be divided into two categories according to the different causes: traumatic femoral head necrosis and non-traumatic femoral head necrosis. Traumatic femoral head necrosis refers to femoral head necrosis secondary to hip trauma, which is a common cause of femoral head necrosis. Femoral head and neck fracture, hip dislocation, and severe hip sprain or contusion can all cause femoral head necrosis; non-traumatic femoral head necrosis refers to femoral head necrosis without traumatic factors, including hormonal femoral head necrosis, alcoholic femoral head necrosis, decompression sickness, sickle cell anemia and other causes of femoral head necrosis, as well as some rare idiopathic femoral head necrosis of unknown causes.

[0004] Western medicine treats femoral head necrosis in two ways: conservative treatment and surgical treatment. For young patients in the early and middle stages, hip preservation treatment can be used, oral anticoagulants and lipid-lowering drugs or combined with hip preservation surgery, but the overall effect is not ideal; for older patients in the late stage, conservative treatment is not effective and hip replacement surgery is required. However, most patients with femoral head necrosis are young and middle-aged, and hip replacement surgery has complications such as postoperative prosthesis loosening, prosthesis life limit, infection and periprosthetic fracture. In particular, young patients are inevitably faced with the risk of multiple repairs due to the limited life of the joint prosthesis, which not only brings great economic pressure to patients, but also seriously affects their physical and mental health.

[0005] In recent years, hip preservation therapy has been a hot topic in the treatment of femoral head necrosis, which meets the natural needs of patients. There is still a lack of ideal methods for hip preservation in Western medicine, which is still mainly based on surgery and only solves local problems. Traditional Chinese medicine has unique advantages in the treatment of hip preservation of femoral head necrosis. Starting from the overall concept, Chinese medicine is selected according to the condition to regulate systemic lesions and achieve the purpose of local treatment.

[0006] At present, although the existing technology discloses some Chinese medicine compositions for treating femoral head necrosis, research on more effective Chinese medicine compositions and promoting the application of traditional Chinese medicine in femoral head necrosis are of great clinical significance for preserving the patient's own joints and delaying or even avoiding joint replacement surgery. Summary of the invention

[0007] In view of the deficiencies in the above-mentioned prior art, the present invention aims to provide a Chinese medicine composition, a Chinese medicine preparation and a preparation method thereof for treating femoral head necrosis. The Chinese medicine has few side effects and good effects, and can be used for hip-preserving treatment of early and middle-stage femoral head necrosis to solve the problems existing in the background technology.

[0008] In order to achieve the above object, the technical solution of the present invention is as follows:

[0009] On the one hand, the present invention discloses a traditional Chinese medicine composition for treating femoral head necrosis, which comprises the following traditional Chinese medicine ingredients by weight: 10-15g of salvia miltiorrhiza, 6-10g of chuanxiong, 10-15g of angelica sinensis, 10-15g of red peony root, 5-10g of earthworm, 3-5g of leech, 5-10g of trigonosciadium japonicum, 5-10g of curcuma, 10-15g of epimedium, 10-15g of chuanduan, 3-5g of cinnamon bark, and 6-10g of liquorice.

[0010] As a further preferred embodiment of the above technical scheme: the Chinese medicine composition comprises the following Chinese medicine ingredients by weight: 15g of Salvia miltiorrhiza, 10g of Chuanxiong, 10g of Angelica sinensis, 12g of Red Peony Root, 6g of Eupolyphaga Seu Steleophaga, 3g of Hirudo, 7g of Trillium, 7g of Curcuma, 10g of Epimedium, 10g of Chuanduan, 4g of Cinnamon Bark, and 6g of Licorice.

[0011] The key pathogenesis of femoral head necrosis is blood stasis and collateral obstruction and liver and kidney deficiency, so the treatment principle and method is to nourish the liver and kidney, promote blood circulation and dredge collaterals, so as to improve the blood circulation of the femoral head and promote the repair of femoral head necrosis. According to this treatment method, the prescription is used, and the prescription is unique and complementary. Salvia miltiorrhiza, Chuanxiong, Angelica sinensis, red peony root, leech, Eupolyphaga sinicus, Tripterygium wilfordii and Curcuma zedoaria are the main drugs to promote blood circulation and dredge collaterals; Chuan Duan and Epimedium are the ministerial drugs to nourish the kidney and strengthen bones; Cinnamon bark is the adjuvant to warm the meridians and dredge collaterals, and help promote blood circulation and remove blood stasis; Licorice is the messenger drug to reconcile the medicinal properties and relieve pain. The blood stasis of femoral head necrosis is not the general blood stasis of fracture, and non-insect drugs cannot cleanse its blood stasis. Therefore, the insect drugs Eupolyphaga sinensis and leech are used to guide the drugs directly to the diseased area, search for blood stasis, and improve the effect of the drugs. Ye Tianshi, a doctor in the Qing Dynasty, believed that insect medicines have the characteristics of good deeds but bad deeds, and pointed out that "when the disease lasts for a long time, the evil and the righteous are mixed in it, and the herbs cannot be effective. We should use insects and ants to expel them and search and remove the evil mixed in the meridians." Insect medicines have dual functions. The meaning of searching and removing is to find the pathogenic factors and remove them. Blood coagulates when it is cold and flows when it is warm. Cinnamon is a warming yang medicine with the effect of warming the meridians and unblocking the vessels. The use of warm medicine cinnamon reflects the guiding role of the classical theory of traditional Chinese medicine and the unique adjuvant value of cinnamon. At the same time, it can warm and resolve phlegm and turbidity. It is used together with red peony root, cold and warm, and helps to activate blood circulation and remove blood stasis, which is conducive to removing blood stasis and promoting new blood. The treatment period of femoral head necrosis with traditional Chinese medicine is generally long, at least half a year or more. Long-term use, especially insect medicine, will cause certain toxic and side effects. Licorice has the effect of harmonizing the medicinal properties, can reduce the toxic and side effects of drugs, promote the synergistic effect of drugs, and has the effect of relieving pain, thereby improving joint function.

[0012] The medicinal mechanism of each Chinese medicine component of the Chinese medicine composition of the present invention is as follows:

[0013] Danshen: has the effect of promoting blood circulation, removing blood stasis and relieving pain;

[0014] Chuanxiong: It has the effects of promoting blood circulation and qi, dispelling wind and relieving pain;

[0015] Angelica: It has the effect of promoting blood circulation and relieving pain;

[0016] Red peony root: has the effect of promoting blood circulation and removing blood stasis;

[0017] Earthworm: It has the effect of breaking blood and removing blood stasis, and repairing tendons and bones;

[0018] Leeches: have the effects of breaking blood, promoting menstruation, removing blood stasis and eliminating symptoms;

[0019] Tripterygium wilfordii: has the effects of breaking blood and promoting qi, eliminating stagnation and relieving pain;

[0020] Curcuma: It has the effects of promoting qi and removing blood, eliminating stagnation and relieving pain;

[0021] Epimedium: It has the effects of nourishing the kidney and strengthening yang, strengthening tendons and bones, and removing wind and dampness;

[0022] Chuanduan: It has the effects of nourishing the liver and kidney, promoting blood circulation, and strengthening tendons and bones;

[0023] Cinnamon: It has the effects of replenishing fire and yang, dispelling cold and relieving pain, and warming and unblocking meridians;

[0024] Licorice: It has the effect of relieving pain and harmonizing various medicines.

[0025] On the other hand, the present invention also discloses a traditional Chinese medicine preparation for treating femoral head necrosis, which is prepared from any of the traditional Chinese medicine compositions described above.

[0026] As a further preferred embodiment: the Chinese medicine preparation is one of decoction, pills, tablets, granules and capsules.

[0027] In another aspect, the present invention discloses a method for preparing a Chinese medicine decoction for treating femoral head necrosis, comprising the following steps:

[0028] S1: Weigh 15g of Danshen, 10g of Chuanxiong, 10g of Angelica, 12g of Red Peony Root, 6g of Eupolyphaga, 3g of Hirudo, 7g of Trigonella, 7g of Curcuma, 10g of Epimedium, 10g of Rhizoma Cynomorii, 4g of Cinnamomum, and 6g of Licorice respectively, and soak them in water for 30min;

[0029] S2: After soaking, boil over high heat and then simmer over low heat for 30 to 45 minutes, and filter the liquid.

[0030] S3: Add water again, boil over high heat, then simmer over low heat for 30 to 45 minutes, and filter the liquid medicine;

[0031] S4: Mix the two liquid medicines filtered in step S2 and step S3, concentrate the mixed liquid medicine, and pack it into bags.

[0032] In a preferred implementation of the above technical solution, the amount of water added in step S1 and step S3 is 10 times and 8 times the amount of the Chinese medicinal raw material, respectively.

[0033] In a preferred embodiment of the above technical solution, the concentration standard for the mixed medicinal liquid in step S4 is to decoct two bags of medicinal liquid for each prescription, 200 mL / bag.

[0034] In another aspect, the present invention further discloses the use of the Chinese medicine composition according to any one of the above items in the preparation of drugs for hip synovitis and / or knee arthritis.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] 1. The Chinese medicine composition of the present invention is based on the classical theory of traditional Chinese medicine and has a unique formula. It uses liver and kidney deficiency and blood stasis, which are the key pathogenesis of femoral head necrosis, as the front-end medication. The various drug ingredients cooperate with each other and complement each other to hit the pathogenesis, so as to nourish the liver and kidney, promote blood circulation and dredge the collaterals, improve blood circulation of the femoral head, and promote the repair of femoral head necrosis. It has significant therapeutic effect and few side effects. It can be used for patients with early and middle-stage femoral head necrosis and late-stage patients who are unwilling to replace joints, as well as patients after hip preservation surgery.

[0037] 2. The Chinese medicine composition of the present invention has good effect in treating femoral head necrosis, and its analgesic effect is significantly better than similar drugs. Some patients use it as an analgesic.

[0038] 3. The Chinese medicine composition of the present invention is based on the TCM theory of "different diseases treated with the same method". In addition to being used to treat femoral head necrosis, it can also be used to treat arthritis such as hip synovitis and knee arthritis, achieving relatively satisfactory therapeutic effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art are briefly introduced below.

[0040] Figure 1 This is the histopathological observation of the femoral head of each group of rabbits in the present invention (HE×200), wherein: A represents the control group; B represents the model group; C represents the experimental group;

[0041] Figure 2 Immunohistochemical staining observation of femoral head tissue of each group of rabbits in the present invention (×400);

[0042] Figure 3 The apoptosis staining results (TUNEL×400) of the femoral head tissue cells of each group of rabbits in the present invention, wherein: A represents the control group; B represents the model group; C represents the experimental group;

[0043] Figure 4 The immunoblot analysis of the femoral head tissue proteins Bax, Bcl-2 and β-actin of each group of rabbits in the present invention;

[0044] Figure 5 The relative expression levels of each group of proteins after correction using the internal reference protein in the present invention;

[0045] Figure 6 The expression of VEGF, eNOs, Bcl-2 and Bax mRNA in femoral head tissue of each group of the present invention;

[0046] Figure 7 The X-ray results of femoral head necrosis of clinical patient 1 of the present invention;

[0047] Figure 8The X-ray results of femoral head necrosis of clinical patient 2 of the present invention;

[0048] Fig. 9 The X-ray results of femoral head necrosis of clinical patient 3 of the present invention;

[0049] Fig.10 The X-ray results of femoral head necrosis of clinical patient 4 of the present invention;

[0050] Fig.11 The X-ray results of femoral head necrosis of clinical patient 5 of the present invention;

[0051] Fig.12 The X-ray results of femoral head necrosis of clinical patient 6 of the present invention;

[0052] Fig.13 The X-ray results of femoral head necrosis of clinical patient 7 of the present invention;

[0053] Fig.14 The X-ray results of femoral head necrosis of clinical patient 8 of the present invention;

[0054] Fig.15 The X-ray results of femoral head necrosis of clinical patient 9 of the present invention;

[0055] Fig.16 This is the X-ray result of femoral head necrosis of clinical patient 10 of the present invention. DETAILED DESCRIPTION

[0056] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments.

[0057] Reference Figure 1-6 The present invention provides a traditional Chinese medicine composition for treating femoral head necrosis. The traditional Chinese medicine composition comprises the following traditional Chinese medicine ingredients by weight: 10-15g of salvia miltiorrhiza, 6-10g of chuanxiong, 10-15g of angelica sinensis, 10-15g of red peony root, 5-10g of earthworm, 3-5g of leech, 5-10g of trigonosciadium japonicum, 5-10g of curcuma, 10-15g of epimedium, 10-15g of chuanduan, 3-5g of cinnamon bark, and 6-10g of liquorice.

[0058] Preferably: the Chinese medicine composition comprises the following Chinese medicine ingredients by weight: 15g of Salvia miltiorrhiza, 10g of Chuanxiong, 10g of Angelica sinensis, 12g of Red Peony Root, 6g of Eupolyphaga Seu Steleophaga, 3g of Hirudo, 7g of Trigonosciadium japonicum, 7g of Curcuma zedoaria, 10g of Epimedium, 10g of Chuanduan, 4g of Cinnamon Bark, and 6g of Licorice.

[0059] In the present invention, the above-mentioned Chinese medicine composition can be made into any one of decoction, pills, tablets, granules and capsules, preferably into decoction, as follows:

[0060] A method for preparing a Chinese medicinal decoction for treating femoral head necrosis comprises the following steps:

[0061] S1: Weigh the Chinese medicinal materials of 15g of Danshen, 10g of Chuanxiong, 10g of Angelica, 12g of Red Peony Root, 6g of Eupolyphaga, 3g of Hirudo, 7g of Trigonella, 7g of Curcuma, 10g of Epimedium, 10g of Rhizoma Cynanchum, 4g of Cinnamomum, and 6g of Licorice respectively by weight, add 10 times the amount of water of the Chinese medicinal materials and soak for 30min;

[0062] S2: After soaking, boil over high heat and then simmer over low heat for 30 to 45 minutes, and filter the liquid.

[0063] S3: After filtering the liquid medicine, add 8 times the amount of water as the raw material of the Chinese medicine again, boil it over high heat, then simmer it over low heat for 30min to 45min, and filter the liquid medicine;

[0064] S4: Mix the medicinal liquids obtained from the two filtrations, and then concentrate the mixed medicinal liquid. The concentration standard is to decoct two bags of medicinal liquid for each medicine, 200mL / bag, and then bag it after concentration.

[0065] Embodiment 1:

[0066] Weigh 15g of Salvia miltiorrhiza, 10g of Chuanxiong, 10g of Angelica sinensis, 12g of Paeonia lactiflora, 6g of Eupolyphaga sinensis, 3g of Hirudo, 7g of Trigonella ternata, 7g of Curcuma zedoaria, 10g of Epimedium, 10g of Rhizoma Cistanches, 4g of Cinnamon Bark, and 6g of Liquorice respectively by weight, add 10 times the amount of water as the raw materials of the traditional Chinese medicine and soak for 30 minutes, boil with high heat first, then simmer for 30 minutes with low heat, filter out the first medicinal liquid, add 8 times the amount of water to the residue, boil with high heat, then simmer for 45 minutes with low heat, filter out the second medicinal liquid, combine the medicinal liquids obtained by the two filtrations, and then concentrate them in a conventional way of traditional Chinese medicine. The concentration standard is to decoct two bags of medicinal liquid for each pair of medicine, 200mL / bag, and bag them after concentration.

[0067] Embodiment 2:

[0068] Weigh 10g of Salvia miltiorrhiza, 6g of Chuanxiong, 10g of Angelica sinensis, 15g of Paeonia lactiflora, 5g of Eupolyphaga sinensis, 3g of Hirudo, 10g of Trillium, 10g of Curcuma zedoaria, 10g of Epimedium, 15g of Rhizoma Cinnamomi, 5g of Cinnamomum cassia, and 6g of Liquorice respectively by weight, add 10 times the amount of water as the raw materials of traditional Chinese medicine, soak for 30 minutes, boil with high heat first, then simmer for 30 minutes with low heat, filter out the first medicinal liquid, add 8 times the amount of water to the residue, boil with high heat, then simmer for 45 minutes with low heat, filter out the second medicinal liquid, combine the medicinal liquids obtained by the two filtrations, and then concentrate them in a conventional way of traditional Chinese medicine. The concentration standard is to decoct two bags of medicinal liquid for each pair of medicine, 200mL / bag, and bag them after concentration.

[0069] Embodiment 3:

[0070] Weigh 15g of Salvia miltiorrhiza, 8g of Chuanxiong, 12g of Angelica sinensis, 12g of Paeonia lactiflora, 10g of Eupolyphaga sinensis, 5g of Hirudo, 10g of Trigonella ternate, 10g of Curcuma zedoaria, 15g of Epimedium, 15g of Rhizoma Cistanches, 5g of Cinnamomum cassia, and 6g of Licorice respectively by weight, add 10 times the amount of water as the raw materials of the traditional Chinese medicine and soak for 30 minutes, boil with high heat first, then simmer for 45 minutes with low heat, filter out the first medicinal liquid, add 8 times the amount of water to the residue, boil with high heat, then simmer for 45 minutes with low heat, filter out the second medicinal liquid, combine the medicinal liquids obtained by the two filtrations, and then concentrate them in a conventional way of traditional Chinese medicine. The concentration standard is to decoct two bags of medicinal liquid for each pair of medicine, 200mL / bag, and bag them after concentration.

[0071] Embodiment 4:

[0072] Weigh 10g of Salvia miltiorrhiza, 8g of Chuanxiong, 10g of Angelica sinensis, 10g of Paeonia lactiflora, 8g of Eupolyphaga sinensis, 4g of Hirudo, 9g of Trigonella ternata, 8g of Curcuma zedoaria, 12g of Epimedium, 12g of Rhizoma Cistanches, 4g of Cinnamomum cassia, and 6g of Licorice respectively by weight, add 10 times the amount of water as the raw materials of the traditional Chinese medicine and soak for 30 minutes, boil with high heat first, then simmer for 45 minutes with low heat, filter out the first medicinal liquid, add 8 times the amount of water to the residue, boil with high heat, then simmer for 30 minutes with low heat, filter out the second medicinal liquid, combine the medicinal liquids obtained by the two filtrations, and then concentrate them in a conventional way of traditional Chinese medicine. The concentration standard is to decoct two bags of medicinal liquid for each pair of medicine, 200mL / bag, and bag them after concentration.

[0073] Embodiment 5:

[0074] Weigh 15g of Salvia miltiorrhiza, 10g of Chuanxiong, 15g of Angelica sinensis, 15g of Red Peony Root, 10g of Eupolyphaga sinensis, 5g of Hirudo, 10g of Trigonella ternate, 10g of Curcuma zedoaria, 15g of Epimedium, 15g of Rhizoma Cistanches, 5g of Cinnamomum cassia, and 10g of Liquorice respectively by weight, add 10 times the amount of water as the raw materials of the traditional Chinese medicine, soak for 30 minutes, boil with high heat first, then simmer for 30 minutes with low heat, filter out the first medicinal liquid, add 8 times the amount of water to the residue, boil with high heat, then simmer for 30 minutes with low heat, filter out the second medicinal liquid, combine the medicinal liquids obtained by the two filtrations, and then concentrate them in a conventional way of traditional Chinese medicine. The concentration standard is to decoct two bags of medicinal liquid for each pair of medicine, 200mL / bag, and bag them after concentration.

[0075] For the Chinese herbal decoction prepared by the present invention, the following animal pharmacology research and clinical efficacy research related experiments were conducted. All items used in the following experiments, including experimental animals, instruments, reagents and other experimental supplies, unless otherwise specified, are commercially available and can be purchased through regular channels. At the same time, the design and implementation of various animal experiments are in accordance with animal welfare and ethical principles, that is, complying with animal protection principles, animal welfare principles and ethical principles. The details are as follows:

[0076] 1. Animal pharmacology experiments:

[0077] Twelve New Zealand rabbits were randomly divided into three groups: control group, model group and experimental group, with 4 rabbits in each group. Except for the control group, the other two groups were injected with 10 μg / kg gluteal muscle of endotoxin, and 24 hours later, 20 mg·kg -1 ·d -1 The left and right gluteal muscles were injected with methylprednisolone sodium succinate alternately for 3 times; after the model was successfully replicated, the dosage was calculated according to the clinical human and animal equivalent doses, the experimental group was given 4.73 g / kg of the Chinese medicine decoction prepared in Example 1 of the present invention for gavage treatment, and the model group and the control group were given an equal amount of normal saline, once a day, for 8 weeks; after the modeling was completed, the bilateral femoral heads of the experimental animals were taken out and placed in 4% paraformaldehyde for storage.

[0078] 1. The effect of the Chinese medicinal decoction of the present invention on the hollow bone pit rate of femoral head tissue;

[0079] like Figure 1 The results of HE staining showed that after 8 weeks of replication of the steroid-induced femoral head necrosis model, the trabecular area of ​​the rabbits in the model group was significantly reduced and there was severe stenosis or fracture, the types of cells in the medullary cavity were reduced, and the number of empty bone pits was significantly increased compared with the control group (P<0.01). After the intervention treatment of the Chinese medicine decoction of the present invention, the types of cells in the medullary cavity of the rabbits in the experimental group were many and abundant, the trabecular structure was complete compared with the model group, and the empty bone pit rate was significantly lower than that of the model group (P<0.01). The comparison results of the empty bone pit rate of the rabbit bone tissue in each group are shown in Table 1.

[0080] Table 1 Comparison of hollow bone pit rate in femoral head tissue of rabbits in each group ( n=3)

[0081] Group Empty bone pit rate (%) Control group 5.40±0.23 Model Group 19.26±0.96** Experimental Group <![CDATA[9.41±0.42 ## ]]> F-number 397.40 P-value P<0.01

[0082] Note: Compared with the control group, **P<0.01; compared with the model group, ## P<0.01

[0083] 2. Effect of the Chinese herbal decoction of the present invention on the expression of vascular-related proteins

[0084] like Figure 2 As shown, pathological sections of the femoral head tissues of each group showed different degrees of brown-yellow positive expression of CD34, CYR61 and VEGF proteins. The experimental results showed that the levels of CD34, CYR61 and VEGF proteins in the femoral head tissues of the model group were significantly lower than those in the control group. Compared with the model group, the results of immunohistochemical localization staining in the experimental group were effectively improved, and the expression of angiogenesis-related factors in the femoral head tissues increased, but there was still a certain gap compared with the normal group.

[0085] 3. The effect of the Chinese herbal decoction of the present invention on apoptosis of cells in the femoral head region of rabbits in each group;

[0086] like Figure 3 As shown, the nuclei of apoptotic cells were stained brown under TUNEL staining, presenting as single cells or scattered, mostly located at the junction of diseased tissue and normal tissue. Compared with the control group, the number of apoptotic cells in the model group increased and the nuclei were darker in color. After treatment with the Chinese medicine decoction of the present invention, the apoptosis of femoral head cells in the experimental group was significantly improved (P<0.01), as shown in Table 2.

[0087] Table 2 Comparison of apoptosis in the femoral head region of rabbits in each group

[0088] Group Apoptosis rate (%) Control group 3.70±0.18 Model Group 20.11±0.68** Experimental Group <![CDATA[8.97±0.35 ## ]]> F-number 1025.57 P-value P＜0.01

[0089] Note: Compared with the control group, **P<0.01; compared with the model group, ## P<0.01

[0090] 4. Effect of the Chinese herbal decoction of the present invention on the expression of Bax and Bcl-2 proteins in femoral head tissue;

[0091] like Figure 4-5 As shown in the Western Blot results, the expression of the pro-apoptotic protein Bax in the model group was significantly increased, while the expression of the anti-apoptotic protein Bcl-2 was inhibited (**P<0.01). After the intervention treatment with the Chinese herbal decoction of the present invention, the expression levels of Bax and Bcl-2 in the experimental group were opposite to those in the model group (## P<0.01), refer to Table 3 for the results.

[0092] Table 3 Expression levels of target proteins in femoral head tissues of each group

[0093]

[0094] 5. Effect of the Chinese herbal decoction of the present invention on the mRNA expression of VEGF, eNOs, Bcl-2 and Bax in rabbit femoral head tissue;

[0095] Reference Figure 6 Compared with the control group, the expression levels of angiogenesis-related factors VEGF and eNOs, and anti-apoptotic gene Bcl-2 in the femoral head tissue of the model group were significantly reduced, while the expression of pro-apoptotic gene Bax was increased (*P<0.05, **P<0.01). After intervention with the Chinese medicine decoction of the present invention, the expression of Bax mRNA in the experimental group was inhibited, and the expression levels of VEGF, eNOs and Bcl-2 mRNA were significantly increased compared with the model group ( ## P<0.01). The results are shown in Table 4.

[0096] Table 4 Expression levels of mRNA in femoral head tissue of each group ( n=3)

[0097]

[0098]

[0099] 2. Clinical efficacy observation:

[0100] A total of 60 patients who visited the orthopedic outpatient clinic of the First Affiliated Hospital of Anhui University of Chinese Medicine were randomly divided into two groups according to the random number table method. There were 30 cases in the control group, including 17 males and 13 females, aged 27-59 years old, with an average age of (42.1±9.7) years old, and a disease course of 4-25 months, with an average age of (14.6±5.3) months; there were 30 cases in the treatment group, including 16 males and 14 females, aged 24-63 years old, with an average age of (43.5±10.2) years old, and a disease course of 3-24 months, with an average age of (13.7±4.8) months. The International Association for Circulation Osteology (ARCO) staging included 15 hips at stage I, 22 hips at stage II, and 8 hips at stage IIIA.

[0101] For 30 patients with early and middle stage femoral head necrosis (ONFH), all were treated with the Chinese medicine decoction prepared in Example 1 of the present invention, and 30 patients in the control group were treated with Xianling Gubao tablets for control observation. During the treatment, the drugs were used respectively, and the reaction indicators of the patients were measured and recorded, and the relevant results are shown in Tables 5-8.

[0102] Table 5 Comparison of clinical efficacy between the two groups

[0103] Group n cure Improvement Not cured Total effective rate (%) Treatment Group 30 16 13 1 96.7* Control group 30 9 14 7 76.7

[0104] As shown in Table 5, the total effective rate of the treatment group was 96.7% (29 / 30), and the total effective rate of the control group was 76.7% (23 / 30). The therapeutic effect of the treatment group was significantly better than that of the control group (P<0.05).

[0105] Table 6 Comparison of VAS treatment scores between the two groups before and after treatment

[0106] Group n Before treatment After treatment Treatment Group 30 6.13±2.01 <![CDATA[3.61±2.51 *△ ]]> Control group 30 6.25±1.86 <![CDATA[4.97±1.58 * ]]>

[0107] Note: Compared with the group before treatment, *P<0.05; compared with the control group after treatment, △ P<0.05

[0108] According to the VAS scores of the two groups before and after treatment in Table 6, the VAS scores and total scores of the two groups after treatment were lower than those before treatment (P<0.05), and the analgesic effect of the treatment group after treatment was better than that of the control group (P<0.05).

[0109] Table 7 Comparison of Harris treatment scores between the two groups before and after treatment

[0110]

[0111] Note: Compared with the group before treatment, *P<0.05; compared with the control group after treatment, △ P<0.05

[0112] As shown in the comparison results in Table 7, after treatment, the Harris scores and total scores of the two groups were higher than those before treatment (P<0.05), and the Harris scores and total scores of the treatment group after treatment were higher than those of the control group (P<0.05).

[0113] Table 8 Comparison of imaging between the two groups before and after treatment

[0114]

[0115] From the comparison results in Table 8, it can be seen that after treatment, the imaging-based ARCO staging of the hip joint, the area of ​​femoral head necrosis, femoral head collapse and the degree of osteoarthritis in the two groups were improved compared with those before treatment (P<0.05), and the imaging changes after treatment in the treatment group were better than those in the control group (P<0.05).

[0116] 3. Some clinical patient cases:

[0117] Patient 1: Zhang, female, 27 years old, left hip pain for more than 7 months, right hip pain for 2 weeks. She has a history of long-term use of hormones for systemic lupus erythematosus. X-ray film of femoral head necrosis (Ficat stage III on the left, stage II on the right) Figure 7 ,like Figure 7 Middle (a), Figure 7 (b) shows the bilateral hip joint anteroposterior and frog-shaped radiographs of patient 1 before treatment. The density of the femoral heads on both sides is uneven, especially on the left side, with patchy increased density and cystic low density. Figure 7 Middle (c), Figure 7 Middle (d) shows the bilateral hip joint anteroposterior and frog position radiographs 3 months after treatment. The density of the bilateral femoral heads is slightly uneven. Figure 7 Middle (e), Figure 7 Middle (f) shows the AP and frog-shaped radiographs of bilateral hip joints one year after treatment. The density of the right femoral head is relatively uniform, the collapsed area of ​​the left femoral head becomes smooth, and there is no obvious narrowing of the joint space.

[0118] Patient 2: Chu, male, 49 years old, left hip pain for 4 months, right hip asymptomatic. History of long-term use of hormones for chronic kidney disease. X-ray of left femoral head necrosis (Ficat stage III) Figure 8 ,like Figure 8 Middle (a), Figure 8 (b) shows the bilateral hip joint anteroposterior and frog-shaped radiographs of patient 2 before treatment. The left femoral head articular surface is not smooth, and patchy low-density areas can be seen. Figure 8 Middle (c), Figure 8 Middle (d) shows the bilateral hip joint anteroposterior and frog position radiographs 3 months after treatment, with a patchy low-density area in the left femoral head and a slightly uneven density in the right femoral head; Figure 8 Middle (e), Figure 8 Middle (f) shows the bilateral hip joint AP and frog position radiographs one year after treatment. The density of the bilateral femoral heads is uneven, the shape is basically smooth, and the joint space is normal.

[0119] Patient 3: Zhang, female, 31 years old, bilateral hip pain for more than 8 months. Unknown cause. X-ray of femoral head necrosis (Ficat stage III on the left, stage II on the right) Fig. 9 ,like Fig. 9 Middle (a), Fig. 9 The bilateral hip joint anteroposterior and frog-shaped radiographs of patient 3 before treatment shown in (b) show that the femoral head density of both sides of patient 3 is uneven, the left femoral head is irregular, the joint surface is not smooth, and a cystic low-density shadow can be seen; Fig. 9 Middle (c), Fig. 9 Middle (d) shows the bilateral hip joint anteroposterior and frog position radiographs 3 months after treatment. The density of the bilateral femoral heads is slightly uneven and the contour is not smooth. Fig. 9 Middle (e), Fig. 9 Middle (f) shows the AP and frog-shaped radiographs of bilateral hip joints one year after treatment. The density of the right femoral head is relatively uniform, the morphology of the left femoral head is still good, and there is no obvious narrowing of the joint space.

[0120] Patient 4: Wei, male, 24 years old, right hip pain for more than half a year. The cause is unknown. X-ray and MRI of right femoral head necrosis (right Ficat stage III) Fig.10 ,like Fig.10 Middle (a), Fig.10 The bilateral hip joint AP radiographs and MRIs of patient 4 before treatment shown in (b) show uneven density of the right femoral head, mild collapse, and cystic low-density shadows; Fig.10 Middle (c), Fig.10 Middle (d) shows the AP radiographs of the hip joint after 3 and 6 months of treatment. The density of the right femoral head is slightly uneven, and the contour is smooth. Fig.10 Middle (e), Fig.10 Middle (f) shows bilateral frog-shaped radiographs of the hip joints one year after treatment. The density of the right femoral head is relatively uniform, and no obvious narrowing of the joint space is observed.

[0121] Patient 5: Zheng, male, 40 years old, had left hip pain for more than 2 months. He had a history of alcoholism. X-ray of left femoral head necrosis Fig.11 ,like Fig.11 Middle (a), Fig.11 The bilateral hip joint anteroposterior radiographs of patient 5 before treatment shown in (b) show that the density of the left femoral head of patient 5 is uneven, with cystic low-density shadows and no collapse; Fig.11 Middle (c), Fig.11 Middle (d) is a frog-shaped radiograph of the hip joint 3 months after treatment. The left femoral head has cystic changes and a smooth contour. Fig.11 Middle (e), Fig.11 Middle (f) is the bilateral frog-shaped radiographs of the hip joints one year after treatment. The cystic area of ​​the left femoral head becomes smaller, the head shape is smooth, and there is no obvious narrowing of the joint space.

[0122] Patient 6: Pan, male, 42 years old, had left hip pain for more than half a year and had a history of alcoholism. X-ray of left femoral head necrosis (left Ficat II stage) Fig.12 ,like Fig.12 Middle (a), Fig.12 (b) shows the bilateral anteroposterior and frog-shaped radiographs of the hip joints of patient 6 before treatment. The density of the left femoral head is uneven, with a cystic low-density shadow. Fig.12 Middle (c), Fig.12 Middle (d) shows the frog-frontal radiograph of the hip joint 3 months after treatment, with cystic changes in the left femoral head; Fig.12 Middle (e), Fig.12 Middle (f) shows bilateral frog-shaped radiographs of the hip joints one year after treatment. The cystic area of ​​the left femoral head becomes smaller and slightly collapsed, but no obvious narrowing of the joint space is observed. The pain is relieved and the function is good after follow-up.

[0123] Patient 7: Yu Moumou, female, 42 years old, left hip pain for more than 5 months, with a history of hormone use. Bilateral femoral head necrosis X-ray (left Ficat III stage) Fig.13 ,like Fig.13 The bilateral anteroposterior radiographs of the hip joints of patient 7 before treatment shown in (a) show uneven density of the left femoral head, with cystic low-density shadows and mild collapse; Fig.13 Middle (b) shows the bilateral hip joint AP radiographs 3 months after treatment, and the density cystic area of ​​the left femoral head has been reduced; Fig.13 Middle (c) shows the bilateral hip joint anteroposterior radiographs after 9 months of treatment. The cystic area of ​​the left femoral head has been reduced, the femoral head shape is basically smooth, and there is no obvious narrowing of the joint space. Fig.13 Middle (d) shows the bilateral hip joint AP radiographs one year after treatment. The density of the left femoral head is slightly uneven, but the shape is basically smooth, and there is no obvious narrowing of the joint space.

[0124] Patient 8: Zhou, male, 44 years old, had left hip pain for more than 5 months and had a history of hormone use. X-ray of left femoral head necrosis (left Ficat stage III) Fig.14 ,like Fig.14 Middle (a), Fig.14 The bilateral hip joint anteroposterior and frog-shaped radiographs of patient 8 before treatment shown in (b) show that the left femoral head density of patient 8 is cystic and low-density, with slight collapse; Fig.14 Middle (c), Fig.14 Middle (d) shows a frog-shaped radiograph of the hip joint 3 months after treatment. Cystic changes were found in the left femoral head, but the collapse did not worsen. Fig.14 Middle (e), Fig.14 Middle (f) shows bilateral frog-shaped radiographs of the hip joints one year after treatment. The cystic area of ​​the left femoral head has become smaller, the head shape has basically returned to smoothness, and there is no obvious narrowing of the joint space.

[0125] Patient 9: Liu, female, 31 years old, left hip pain for 2 months, right hip pain for more than 4 months, unknown cause. Bilateral femoral head necrosis X-ray (left and right Ficat II stage) Fig.15 ,like Fig.15 Middle (a), Fig.15 (b) shows the bilateral hip joint anteroposterior and frog-shaped radiographs of patient 9 before treatment. The density of the bilateral femoral heads is uneven, and cystic low-density shadows can be seen. Fig.15 Middle (c), Fig.15 Middle (d) shows the bilateral hip joint anteroposterior and frog position radiographs 3 months after treatment. The density of the bilateral femoral heads is slightly uneven, and there is no collapse. Fig.15 Middle (e), Fig.15 Middle (f) shows the AP and frog-view radiographs of bilateral hip joints one year after treatment. The cystic areas of the bilateral femoral heads were reduced, with no obvious collapse and no obvious narrowing of the joint space.

[0126] Patient 10: Fu, male, 26 years old, right hip pain for more than 7 months. Used hormones. X-ray of right femoral head necrosis (right Ficat stage III) Fig.16 ,like Fig.16 Middle (a), Fig.16 The bilateral hip joint anteroposterior and frog-shaped radiographs of patient 10 before treatment shown in (b) show a large range of uneven density, cystic low-density shadows, and mild collapse in the right femoral head; Fig.16 Middle (c), Fig.16 Middle (d) shows the AP and frog view of the hip joint 3 months after treatment. The density of the right femoral head is slightly uneven, and the range of cystic changes has been reduced. Fig.16 Middle (e), Fig.16 Middle (f) shows bilateral frog-shaped AP radiographs of the hip joints one year after treatment. The density of the right femoral head is relatively uniform, the cystic area is significantly reduced, the femoral head is basically smooth, and there is no obvious narrowing of the joint space.

[0127] The detailed description of the above embodiments is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the invention. Based on the embodiments in the present invention, it is only used to illustrate the technical solution of the present invention rather than to limit it. Other modifications or equivalent substitutions made by ordinary technicians in the field to the technical solution of the present invention, as long as they do not depart from the spirit and scope of the technical solution of the present invention, should be included in the scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for treating femoral head necrosis, characterized in that: The traditional Chinese medicine composition comprises the following traditional Chinese medicine ingredients by weight: 10-15g of salvia miltiorrhiza, 6-10g of chuanxiong, 10-15g of angelica sinensis, 10-15g of red peony root, 5-10g of earthworm, 3-5g of leech, 5-10g of triangularis, 5-10g of curcuma, 10-15g of epimedium, 10-15g of chuanduan, 3-5g of cinnamon bark and 6-10g of liquorice.

2. A Chinese medicine composition for treating femoral head necrosis according to claim 1, characterized in that: The traditional Chinese medicine composition comprises the following traditional Chinese medicine ingredients by weight: 15g of salvia miltiorrhiza, 10g of chuanxiong, 10g of angelica sinensis, 12g of red peony root, 6g of earthworm, 3g of leech, 7g of triangularis, 7g of curcuma, 10g of epimedium, 10g of chuanduan, 4g of cinnamon bark and 6g of liquorice.

3. A Chinese medicine preparation for treating femoral head necrosis, characterized in that: The traditional Chinese medicine preparation is prepared from the traditional Chinese medicine composition described in any one of claims 1 to 3.

4. A Chinese medicine preparation for treating femoral head necrosis according to claim 3, characterized in that: The traditional Chinese medicine preparation is one of decoction, pill, tablet, granule and capsule.

5. A method for preparing a Chinese medicinal decoction for treating femoral head necrosis, characterized in that: The following steps are involved: S1: Weigh 15g of Danshen, 10g of Chuanxiong, 10g of Angelica, 12g of Red Peony Root, 6g of Eupolyphaga, 3g of Hirudo, 7g of Trigonella, 7g of Curcuma, 10g of Epimedium, 10g of Rhizoma Cynomorii, 4g of Cinnamomum, and 6g of Licorice respectively, and soak them in water for 30min; S2: After soaking, boil over high heat and then simmer over low heat for 30 to 45 minutes, and filter the liquid. S3: Add water again, boil over high heat, then simmer over low heat for 30 to 45 minutes, and filter the liquid medicine; S4: Mix the two liquid medicines filtered in step S2 and step S3, concentrate the mixed liquid medicine, and pack it into bags.

6. The method for preparing a Chinese medicinal decoction for treating femoral head necrosis according to claim 5, characterized in that: In step S1 and step S3, the amount of water added is 10 times and 8 times the amount of the Chinese medicinal raw material, respectively.

7. The method for preparing a Chinese medicinal decoction for treating femoral head necrosis according to claim 5, characterized in that: In step S4, the concentration standard for the mixed medicinal liquid is to decoct two bags of medicinal liquid for each medicine, 200 mL / bag.

8. Use of the Chinese medicine composition according to any one of claims 1-2 in the preparation of drugs for hip synovitis and / or knee arthritis.

Images