A pharmaceutical composition for treating femoral head necrosis and a preparation method thereof

Abstract

The present application relates to the technical field of femoral head necrosis, and particularly relates to a medicine composition for treating femoral head necrosis and a preparation method thereof. The medicine composition is prepared from the following raw materials in parts by weight: 3-30 parts of poria cocos, 3-30 parts of red peony root, 3-30 parts of radix codonopsis, 3-30 parts of fried atractylodes, 3-30 parts of angelica sinensis, 3-30 parts of chuanxiong rhizome, 3-30 parts of cassia twig, 3-30 parts of prepared rehmannia, 3-30 parts of deer antler, 3-30 parts of chuan niuxi, and 3-30 parts of dried tangerine or orange peel. The medicine composition has good efficacy, and the medicine components and component content have high stability.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of femoral head necrosis, and in particular to a pharmaceutical composition for treating femoral head necrosis and a preparation method thereof. BACKGROUND

[0002] Femoral head necrosis (ONFH) is a refractory disease in orthopedics with a high rate of disability, which is caused by the death of bone cell components due to blood circulation disorders in the femoral head. There is currently no western medicine for treating femoral head necrosis, and 80% of patients have to undergo artificial joint replacement due to femoral head collapse and severe joint function limitation. However, most patients with femoral head necrosis are young adults, and the service life of artificial joints is only a few years, so patients may need to undergo multiple surgeries, which brings endless pain to their life and work.

[0003] Traditional Chinese medicine can alleviate symptoms, delay disease progression, and postpone or avoid joint replacement for treating femoral head necrosis. For example, CN112057582A, published on December 11, 2020, discloses a Chinese herbal medicine for treating femoral head necrosis and a preparation method thereof, which is composed of 32 kinds of traditional Chinese medicines such as notoginseng, red peony root, myrrh, white peony root, dragon's blood, and safflower, and is prepared by drying, crushing, decocting, and then filling into sealed bottles and storing in an environment at room temperature of 6-12℃. The above-mentioned compound traditional Chinese medicine has a large number of components and a large dose, contains expensive deer horn, is inconvenient to take, and causes heavy economic burden on patients, and its main function is to tonify qi and promote blood circulation.

[0004] The present inventors have found through more than 30 years of clinical practice that the occurrence of femoral head necrosis is closely related to the spleen and kidney, and in the early and middle stages, it is mostly due to deficiency of spleen qi, phlegm and blood stasis blocking collaterals, and in the late stage, it is mostly due to deficiency of liver and kidney. The treatment is mainly to invigorate the spleen, remove phlegm, tonify the kidney and strengthen the bones.

[0005] CN101926906A, published on December 29, 2010, discloses a traditional Chinese medicine composition for treating early and middle stage femoral head necrosis with the functions of invigorating the spleen, removing phlegm, promoting blood circulation, dredging collaterals, tonifying the kidney and generating bones. The composition is composed of 12 kinds of traditional Chinese medicines, such as poria cocos, cassia twig, atractylodes, radix codonopsis, red peony root, angelica, chuanxiong, prepared rehmannia, licorice, radix pseudo-ginseng, ground bug, and deerhorn glue. The above-mentioned traditional Chinese medicine composition contains 7 kinds of traditional Chinese medicines, such as red peony root, poria cocos, cassia twig, radix codonopsis, angelica, chuanxiong, and prepared rehmannia, and also contains 5 kinds of traditional Chinese medicines, such as radix pseudo-ginseng, ground bug, deerhorn glue, atractylodes, and licorice. Among them, radix pseudo-ginseng and ground bug are "poisonous" medicinal materials in the pharmacopoeia, and modern research shows that they have irritant, nephrotoxicity, embryotoxicity, and teratogenic effects; there are also reports that there are excessive aflatoxins in ground bug slices on the market; deerhorn glue is a processed product of the original medicinal material, containing auxiliary materials such as icing sugar, soybean oil, and yellow rice wine, and has poor controllability of quality and relatively high price; although licorice has the functions of tonifying middle qi and relieving pain, it should not be taken for a long time.

[0006] In summary, in the prior art, there is a lack of a medicine composition for treating femoral head necrosis with less medicine taste, without toxic and expensive medicinal materials, and suitable for long-term use. SUMMARY

[0007] The present application provides a medicine composition for treating femoral head necrosis and a preparation method thereof, to solve the problems of complex medicine components, multiple medicine tastes, toxic components in medicinal materials, unstable efficacy components and component content, high medicine cost, and unsuitable long-term use in the prior art.

[0008] The present application provides a medicine composition prepared from the following raw materials in parts by weight: 3-30 parts of Poria cocos, 3-30 parts of Red Peony Root, 3-30 parts of Codonopsis, 3-30 parts of Fried Atractylodes, 3-30 parts of Angelica, 3-30 parts of Chuanxiong, 3-30 parts of Cassia twig, 3-30 parts of Prepared Rehmannia, 3-30 parts of Deer Antler, 3-30 parts of Cow's Knee, and 3-30 parts of Tangerine Peel.

[0009] Preferably, the medicine composition is prepared from the following raw materials in parts by weight: 13-17 parts of Poria cocos, 10-14 parts of Red Peony Root, 10-14 parts of Codonopsis, 13-17 parts of Fried Atractylodes, 8-12 parts of Angelica, 8-12 parts of Chuanxiong, 10-14 parts of Cassia twig, 13-17 parts of Prepared Rehmannia, 8-12 parts of Deer Antler, 8-12 parts of Cow's Knee, and 8-12 parts of Tangerine Peel.

[0010] During the research and development of the present application, attempts were made to combine various medicinal materials commonly used for treating femoral head necrosis, such as Deer Antler glue and Deer Antler cream with the functions of warming kidney yang and strengthening bones and muscles, White Atractylodes with the functions of benefiting qi and invigorating spleen, promoting water and reducing swelling, and Earthworm with the function of continuing bones and muscles, but none of them could achieve the effects of the present application. Moreover, the amount of the raw materials is also very important, and changing the amount of the raw materials of the present application cannot achieve the effects of the present application.

[0011] In particular, the medicine composition of the present application selects four medicines, namely, Deer Antler, Fried Atractylodes, Cow's Knee, and Tangerine Peel. The quality of Deer Antler is relatively stable; in the present application, Fried Atractylodes is superior to White Atractylodes in terms of tonifying qi and invigorating spleen; Cow's Knee has the functions of removing blood stasis and unblocking channels and joints; and Tangerine Peel has the function of invigorating spleen and reducing phlegm. Compared with the disclosed medicine compositions, the medicine composition of the present application has less medicine taste, without toxic and expensive medicines. In clinical practice, it can achieve the therapeutic effects of relieving the pain symptoms of patients with femoral head necrosis, improving joint function, promoting bone repair, and regulating blood lipids.

[0012] Preferably, the pharmaceutical composition of the present application is prepared from the following raw materials in the following proportions by weight: poria cocos 14-16 parts, red peony root 11-13 parts, radix codonopsitis 11-13 parts, fried atractylodes 14-16 parts, angelica 9-11 parts, chuanxiong 9-11 parts, cassia twig 11-13 parts, prepared rehmannia 14-16 parts, deer horn 9-11 parts, chuan- nicker 9-11 parts, and dried tangerine or orange peel 9-11 parts.

[0013] More preferably, the pharmaceutical composition of the present application is prepared from the following raw materials in the following proportions by weight: poria cocos 15 parts, red peony root 12 parts, radix codonopsitis 12 parts, fried atractylodes 15 parts, angelica 10 parts, chuanxiong 10 parts, cassia twig 12 parts, prepared rehmannia 15 parts, deer horn 10 parts, chuan- nicker 10 parts, and dried tangerine or orange peel 10 parts. The pharmaceutical effect of the medicine prepared from the above-mentioned raw materials in the above-mentioned proportions is particularly outstanding.

[0014] The present application also provides a preparation method of the pharmaceutical composition, comprising the following steps:

[0015] ① poria cocos, red peony root, radix codonopsitis, fried atractylodes, angelica, chuanxiong, cassia twig, prepared rehmannia, chuan- nicker, and dried tangerine or orange peel are added to water in an amount of 11-13 times, and decocted for 1.2-1.8 hours to obtain decocted liquid, and the decocted liquid is separated to obtain medicinal liquid and medicinal residue, and the medicinal liquid is concentrated to obtain concentrated liquid;

[0016] ② the medicinal residue obtained in step ① is added to water in an amount of 9-11 times, and decocted for 1.2-1.8 hours to obtain decocted liquid, and the decocted liquid is separated to obtain medicinal liquid and medicinal residue, and the medicinal liquid is combined with the concentrated liquid of step ① and then concentrated to obtain concentrated liquid;

[0017] ③ the medicinal residue obtained in step ② is added to water in an amount of 9-11 times, and decocted for 1.2-1.8 hours to obtain decocted liquid, and the decocted liquid is separated to obtain medicinal liquid and medicinal residue, and the medicinal liquid is combined with the concentrated liquid of steps ① and ② and then concentrated to obtain final concentrated liquid;

[0018] ④ the final concentrated liquid obtained in step ③ is dried under reduced pressure, and then pulverized to obtain dry paste, and then the dry paste is pulverized to obtain dry paste powder. The above-mentioned preparation method can ensure the stability of the medicinal components and the component content of the pharmaceutical composition.

[0019] Preferably, the separation of the decocted liquid in steps ①-③ is performed by filtration.

[0020] Preferably, the dry paste is obtained by sieving after pulverization in step ④.

[0021] According to the preparation method of the pharmaceutical composition of the present application, the concentration in step ① is performed by concentrating the medicinal liquid to a relative density of about 1.10-1.15.

[0022] Preferably, the concentration in step ① is performed at a temperature of 60-90℃.

[0023] The concentration in step 2 is to concentrate the medicinal liquid to a relative density of about 1.10-1.15.

[0024] Preferably, the concentration in step 2 is at a temperature of 60-90℃.

[0025] The concentration in step 3 is to concentrate the medicinal liquid to a relative density of about 1.10-1.15.

[0026] Preferably, the concentration in step 3 is at a temperature of 60-90℃.

[0027] Preferably, the concentration in step 3 is combined with the drying method of the enterprise to concentrate to a suitable relative density.

[0028] According to the preparation method of the pharmaceutical composition of the present application, the extract concentration of the final concentrated liquid in step 3 is 1.10 / cm 3 .

[0029] According to the preparation method of the pharmaceutical composition of the present application, the temperature for the reduced pressure drying in step 4 is 60-90℃, preferably 60-85℃, and more preferably 80℃.

[0030] According to the preparation method of the pharmaceutical composition of the present application, it further comprises step 5: uniformly mixing the dry extract powder obtained in step 4 with dextrin, and dry compression granulation.

[0031] Preferably, step 5 further comprises: passing the granules through No. 1 and No. 5 sieves, and re-compressing the granules that do not pass through No. 1 sieve and the fine powder that passes through No. 5 sieve to obtain medicinal granules.

[0032] In some embodiments of the present application, the above components are prepared into the pharmaceutical of the present application by the following method:

[0033] 1. Poria cocos, red peony root, codonopsis root, fried atractylodes, angelica, chuanxiong, cassia twig, prepared rehmannia root, chuanxiong, dried tangerine peel, add 12 times the amount of water, decoct for 1.5 hours, filter, and concentrate the filtrate;

[0034] 2. Add 10 times the amount of water to the residue obtained in step 1, decoct for 1.5 hours, filter, and combine the filtrate with the concentrated liquid in step 1 to continue concentrating;

[0035] 3. Add 10 times the amount of water to the residue obtained in step 2, decoct for 1.5 hours, filter, and combine the filtrate with the concentrated liquid in steps 1 and 2 to continue concentrating;

[0036] 4. Reduce pressure dry (80℃) the concentrated liquid obtained in step 3, crush, sieve, calculate the weight of the dry extract, and obtain dry extract powder;

[0037] ⑤ The dry paste powder obtained in step ④ is mixed with a certain amount of dextrin, dry-pressed into granules, and sieved through a No. 1 and a No. 5 sieve to obtain granules. The granules that do not pass through the No. 1 sieve are combined with the fine powder that passes through the No. 5 sieve, and the mixture is re-pressed into granules to obtain the drug granules and pack them. Through the improvement of the raw material composition, the raw material ratio, and the preparation method of the drug composition, the obtained drug composition has good efficacy and very good stability.

[0038] Preferably, the weight ratio of the dry paste powder to dextrin in step ⑤ is 1:0.2-0.3, preferably 1:0.25. Through the above weight ratio of the dry paste powder to dextrin, the obtained granules have better effects.

[0039] The application further provides a drug for treating femoral head necrosis, which comprises the drug composition or the drug composition prepared by the preparation method.

[0040] The drug for treating femoral head necrosis according to the application has an oral preparation form.

[0041] Preferably, the oral preparation comprises granules, decoction, tablets, powder, paste, pills, capsules, powder, or oral liquid.

[0042] The application further provides the use of the drug composition or the drug prepared by the preparation method in the preparation of a drug for treating any one of the following:

[0043] 1) a drug for regulating blood lipids in patients with femoral head necrosis;

[0044] 2) a drug for promoting bone repair;

[0045] 3) a drug for improving hip joint function.

[0046] The technical solution of the present application is based on the understanding of the pathogenesis and treatment principles of femoral head necrosis in traditional Chinese medicine, and refers to the modern pharmacological research results, and is combined according to the prescription principle of 'invigorating spleen, reducing phlegm, promoting blood circulation and unblocking collaterals'. In the prescription, poria and red peony root are the monarch drugs, both of which have the effects of invigorating spleen, reducing phlegm and removing dampness, and also have the effects of promoting blood circulation and unblocking collaterals, and can invigorate spleen, reduce phlegm, promote blood circulation and unblock collaterals, and have the effects of treating both symptoms and root causes; dangshen, fried atractylodes, chuanxiong, angelica, cassia twig and dried tangerine or orange peel are the ministerial drugs, among which dangshen, fried atractylodes and dried tangerine or orange peel can tonify qi and invigorate the spleen, dry dampness and reduce phlegm, so as to assist poria in invigorating the spleen and reducing phlegm; angelica can tonify blood and promote blood circulation, chuanxiong can promote blood circulation and relieve pain, and cassia twig can warm and unblock meridians, and the three drugs are used together to enhance the effect of red peony root in promoting blood circulation and unblocking collaterals, and the prescription is used to reflect the pathogenesis of'spleen deficiency causing phlegm, phlegm causing blood stasis, and blood stasis causing arthralgia' and the treatment principle of 'treating phlegm and blood stasis together' of femoral head necrosis. Radix rehmanniae and antler are the auxiliary drugs, which are used to specially treat the kidney syndrome at the disease site, and the prescription for early and middle stages of femoral head necrosis takes into account the kidney marrow, can play the role of preventing disease from getting worse, and can also generate marrow and strengthen bones, which is another innovation point of the present application; chuanxiong is the ministerial drug, which is used in three ways, that is, invigorating the spleen and tonifying qi with poria, assisting the effect of cassia twig in promoting blood circulation and unblocking collaterals, and guiding the other drugs downward.

[0047] The raw materials of the pharmaceutical composition of the present application have the following effects:

[0048] Poria: sweet and bland, neutral. Belongs to heart, lung, spleen and kidney channels. It can benefit water and remove dampness, invigorate the spleen and calm the heart. It is used for edema, oliguria, dizziness and palpitation due to phlegm, spleen deficiency, poor appetite, diarrhea, instability of heart and mind, and insomnia due to palpitation.

[0049] Red peony root: bitter and cold. Belongs to liver channel. It can clear heat and cool blood, dispel blood stasis and relieve pain. It is used for heat entering blood and ying, warm toxic eruption, hematemesis and metrorrhagia, red and swollen eyes, liver stagnation and hypochondriac pain, amenorrhea and dysmenorrhea, abdominal mass, injury, and abscess and ulcer.

[0050] Dangshen: sweet and neutral. Belongs to spleen and lung channels. It can invigorate the spleen and lung, nourish blood and generate fluid. It is used for spleen and lung deficiency, poor appetite, cough and shortness of breath, deficiency of qi and blood, sallow complexion, palpitation and shortness of breath, dry mouth and thirst, and internal heat and polydipsia.

[0051] Fried atractylodes: bitter and sweet, warm. Belongs to spleen and stomach channels. It can invigorate the spleen and tonify qi, dry dampness and reduce water, stop sweating and calm the fetus. It is used for spleen deficiency, poor appetite, abdominal distension and diarrhea, phlegm-dampness and dizziness, edema, spontaneous sweating and unstable fetus.

[0052] Angelica: sweet and pungent, warm. Belongs to liver, heart and spleen channels. It can tonify blood, regulate menstruation and relieve pain, moisten the intestines and relieve constipation. It is used for blood deficiency and sallow complexion, dizziness and palpitation, irregular menstruation and dysmenorrhea, cold abdominal pain, arthralgia due to wind and dampness, injury, abscess and ulcer, and dry constipation. Wine angelica can promote blood circulation and unblock channels. It is used for irregular menstruation and dysmenorrhea, arthralgia due to wind and dampness, and injury.

[0053] Chuanxiong: acrid, warm. Liver, gallbladder, pericardium meridian. Promote blood circulation and qi flow, dispel wind and relieve pain. For chest pain, chest pain, chest pain, sprains and contusions, irregular menstruation, amenorrhea and dysmenorrhea, abdominal mass pain, headache, rheumatism and pain.

[0054] Cassia twig: acrid, sweet, warm. Heart, lung, bladder meridian. Sweating and dispelling cold, warming meridians, assisting yang and transforming qi, regulating and descending qi. For colds, abdominal pain, blood cold amenorrhea, joint pain, phlegm, edema, palpitations, and galloping.

[0055] Radix Rehmanniae Preparata: sweet, slightly warm. Liver, kidney meridian. Tonifying blood and yin, nourishing essence and marrow. For blood deficiency, palpitation, irregular menstruation, metrorrhagia, amenorrhea, dysmenorrhea, liver and kidney yin deficiency, lumbago and soreness, bone steaming and heat, night sweating, and internal heat, dizziness, tinnitus, and premature graying.

[0056] Chuanxiong: acrid, warm. Liver, gallbladder, pericardium meridian. Promote blood circulation and qi flow, dispel wind and relieve pain. For chest pain, chest pain, chest pain, sprains and contusions, irregular menstruation, amenorrhea and dysmenorrhea, abdominal mass pain, headache, rheumatism and pain.

[0057] Pericarpium Citri Reticulatae: bitter, acrid, warm. Lung, spleen meridian. Regulating qi and invigorating spleen, drying dampness and reducing phlegm. For abdominal distension, food retention, vomiting and diarrhea, cough and excessive phlegm.

[0058] Antler: salty, warm. Kidney, liver meridian. Warm kidney yang, strengthen bones and muscles, blood circulation and swelling. Deficiency of kidney yang, impotence, night sweating, lumbago and soreness, yin sores and ulcers, initial mastitis, blood stasis and swelling.

[0059] The present application has the following advantages:

[0060] 1. In the traditional Chinese medicine component of the present application, poria cocos and pericarpium citri reticulatae invigorate the spleen and reduce phlegm; red peony root and cassia twig promote blood circulation and remove blood stasis, dredge collaterals and relieve pain; radix codonopsis and fried atractylodes rhizome invigorate the spleen and tonify qi; angelica and radix rehmanniae preparata invigorate the blood and tonify the blood, and the addition of chuanxiong into the blood division regulates qi, so that angelica and radix rehmanniae preparata tonify without stagnation, chuanxiong removes blood stasis and regulates menstruation, and antler warms kidney yang, strengthens bones and muscles, and promotes blood circulation and swelling. Pharmacologically, radix codonopsis can effectively improve hematopoietic function, the main effective components in fried atractylodes rhizome, poria cocos and pericarpium citri reticulatae can promote fat metabolism in blood and adjust the state of vascular microcirculation; the effective components of cassia twig have the effect of expanding blood vessels and improving microcirculation; the main components of blood-activating and stasis-removing drugs such as angelica, radix rehmanniae preparata, chuanxiong and red peony root can effectively promote the proliferation and differentiation of osteoblasts; chuanxiong has the effects of anticoagulation, anti-inflammatory and analgesia; antler contains antler bud stem cell, which can promote bone repair. The above drugs mutually assist each other, and jointly play the role of invigorating the spleen, reducing phlegm, activating blood and dredging collaterals.

[0061] 2. The preparation process of this invention is perfect, and systematically considers a series of issues such as the amount of water added, the decoction time, the concentration method, and the specific gravity of the concentrated paste during the decoction process, so as to ensure the stability of the effective components and component content of each Chinese medicine. At the same time, considering the research on the efficacy and toxicology of Chinese medicine compound prescriptions, the dry paste powder obtained in step ④ can be directly vacuum-packed for research in the above preparation process.

[0062] 3. The pharmaceutical composition of the present invention has few types of raw materials, good clinical efficacy, does not contain toxic medicinal materials, and can achieve better treatment effect for femoral head necrosis when applied.

[0063] 4. By improving the preparation method, this invention can ensure the stability of the active ingredients and their content in the pharmaceutical composition.

[0064] 5. In terms of the preparation process, this invention takes into account a series of issues such as the amount of water added during decoction, the length of decoction time, the specific concentration method, and the specific gravity of the concentrated paste, so as to ensure the stability of the active ingredients and the content of the ingredients in the pharmaceutical composition of this invention.

[0065] 6. This invention can reduce drug costs. The market research price of deer antler contained in the composition of this invention is about RMB 0.88 / g, while the price of deer antler glue is about RMB 5.750 / g. The cost reduction is about RMB 4.00 per gram of raw medicinal material. Based on 12g per day, the cost reduction per person per day is RMB 48.00. Attached Figure Description

[0066] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0067] Figure 1 This is a schematic flowchart of the preparation method of the pharmaceutical composition provided by the present invention. Detailed Implementation

[0068] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0069] Example 1

[0070] The raw materials of the pharmaceutical composition in this embodiment are: 15g of Poria cocos, 12g of Paeonia lactiflora, 12g of Codonopsis pilosula, 15g of stir-fried Atractylodes macrocephala, 10g of Angelica sinensis, 10g of Ligusticum chuanxiong, 12g of Cinnamomum cassia, 15g of Rehmannia glutinosa, 10g of deer antler, 10g of Achyranthes bidentata, and 10g of Citrus reticulata peel.

[0071] The preparation method of the pharmaceutical composition in this embodiment includes the following steps:

[0072] 1. Weigh the raw materials.

[0073] 2. The above eleven ingredients are decocted three times with water. For the first decoction, add 12 times the amount of water and decoct for 1.5 hours. Filter and concentrate the filtrate. For the second decoction, add 10 times the amount of water to the dregs and decoct for 1.5 hours. Filter and combine the filtrate with the first concentrated liquid for further concentration. For the third decoction, add 10 times the amount of water to the dregs and decoct for 1.5 hours. Filter and combine the filtrate with the first two concentrated liquids for further concentration. After concentration, dry under reduced pressure (80℃), pulverize, and sieve to obtain the dry extract powder.

[0074] 3. Mix the dry powder obtained in step 2 with a certain amount of dextrin, dry compress it into granules, and granulate it through sieves No. 1 and No. 5. Combine the granules that do not pass through sieve No. 1 and the fine powder that passes through sieve No. 5, re-press them into granules, and obtain drug granules and package them.

[0075] Example 2

[0076] The raw materials for the pharmaceutical composition in this embodiment are: Poria cocos 5g, Paeonia lactiflora 5g, Codonopsis pilosula 5g, Atractylodes macrocephala (fried) 5g, Angelica sinensis 5g, Ligusticum chuanxiong 5g, Cinnamomum cassia 5g, Rehmannia glutinosa (processed) 5g, Cervi cornu 5g, Achyranthes bidentata 5g, and Citrus reticulata 5g.

[0077] The preparation method of the pharmaceutical composition in this embodiment includes the following steps:

[0078] The above eleven ingredients are decocted three times with water. For the first decoction, add 12 times the amount of water and decoct for 1.5 hours. Filter and concentrate the filtrate. For the second decoction, add 10 times the amount of water to the dregs and decoct for 1.5 hours. Filter and combine the filtrate with the first concentrated liquid for further concentration. For the third decoction, add 10 times the amount of water to the dregs and decoct for 1.5 hours. Filter and combine the filtrate with the first two concentrated liquids for further concentration. After concentration, dry under reduced pressure (80℃), pulverize, and sieve to obtain the dry extract powder.

[0079] Example 3

[0080] The pharmaceutical composition of this embodiment includes the following raw materials: Poria cocos 12g, Paeonia lactiflora 22g, Codonopsis pilosula 15g, Atractylodes macrocephala (fried) 12g, Angelica sinensis 28g, Ligusticum chuanxiong 12g, Cinnamomum cassia 5g, Rehmannia glutinosa (processed) 12g, Cervi cornu 12g, Achyranthes bidentata 15g, and Citrus reticulata 6g.

[0081] Tablets were prepared according to the method in Example 1.

[0082] Example 4

[0083] The pharmaceutical composition of this example comprises the following raw materials: Poria cocos 15g, Red Peony Root 11g, Codonopsis 12g, Fried Atractylodes 16g, Angelica 10g, Chuanxiong 10g, Cassia Bark 13g, Prepared Rehmannia 15g, Deer Antler 10g, Sichuan Cyathula 10g, and Tangerine Peel 10g.

[0084] The pills are prepared according to a conventional preparation process.

[0085] Example 5

[0086] The pharmaceutical composition of this example comprises the following raw materials: Poria cocos 3g, Red Peony Root 30g, Codonopsis 5g, Fried Atractylodes 5g, Angelica 30g, Chuanxiong 15g, Cassia Bark 14g, Prepared Rehmannia 15g, Deer Antler 30g, Sichuan Cyathula 30g, and Tangerine Peel 10g.

[0087] The capsules are prepared according to a conventional preparation process.

[0088] Example 6

[0089] The pharmaceutical composition of this example comprises the following raw materials: Poria cocos 30g, Red Peony Root 4g, Codonopsis 5g, Fried Atractylodes 5g, Angelica 30g, Chuanxiong 5g, Cassia Bark 4g, Prepared Rehmannia 30g, Deer Antler 30g, Sichuan Cyathula 28g, and Tangerine Peel 30g.

[0090] The powder is prepared according to a conventional preparation process.

[0091] Example 7

[0092] The pharmaceutical composition of this example comprises the following raw materials: Poria cocos 25g, Red Peony Root 6g, Codonopsis 15g, Fried Atractylodes 18g, Angelica 15g, Chuanxiong 14g, Cassia Bark 24g, Prepared Rehmannia 26g, Deer Antler 25g, Sichuan Cyathula 12g, and Tangerine Peel 30g.

[0093] The oral agent is prepared according to a conventional preparation process.

[0094] Example 8

[0095] The pharmaceutical composition of this example comprises the following raw materials: Poria cocos 26g, Red Peony Root 16g, Codonopsis 17g, Fried Atractylodes 8g, Angelica 19g, Chuanxiong 12g, Cassia Bark 18g, Prepared Rehmannia 17g, Deer Antler 15g, Sichuan Cyathula 22g, and Tangerine Peel 20g.

[0096] The powder is prepared according to a conventional preparation process.

[0097] Experimental Example 1 Treatment effect of the pharmaceutical composition of the present application on femoral head necrosis

[0098] 1Materials: 48 cases of non-traumatic femoral head necrosis, including 30 males and 18 females, with the youngest being 18 years old and the oldest being 65 years old.

[0099] 2 Method and result

[0100] 2.1 Method: The drug composition (Poria cocos 15g, Red Shaoyao 12g, Dangshen 12g, Fried Baizhu 15g, Dangui 10g, Chuanqiong 10g, Guizhi 12g, Shudihuang 15g, Lujiao 10g, Chuan Niuxi 10g and Chenpi 10g) was water decocted and taken, 1 dose per day, 2 times orally. 3 months was a course of treatment, 1 course of treatment, a total of a course of treatment.

[0101] 2.2 Results

[0102] 2.2.1 Clinical efficacy

[0103] Table 1 Clinical efficacy of each item before and after treatment (n = 48, )

[0104]

[0105] The data were analyzed by paired T test, and the differences between the groups were analyzed. From the statistical analysis results, the hip joint activity, pain and total score of the patients were improved after 3 months of treatment.

[0106] Table 2 Imaging of each item before and after treatment (n = 48, )

[0107]

[0108] The data were analyzed by paired T test, and the differences between the groups were analyzed. From the statistical analysis results, the hip joint activity, pain and total score of the patients were improved after 3 months of treatment.

[0109] 3.3 Changes in blood lipids before and after treatment

[0110] Table 3 Blood lipids before and after treatment (n = 48, )

[0111]

[0112] The data were analyzed by paired T test, and the differences between the groups were analyzed. From the statistical analysis results, the hip joint activity, pain and total score of the patients were improved after 3 months of treatment.

[0113] Experimental example 2:

[0114] Wang, female, 18 years old, due to systemic lupus erythematosus using hormone for 3 months, double hip joint pain, limited activity, after double hip joint check, diagnosis: bilateral femoral head necrosis (bilateral II stage b). Take the water decoction of the pharmaceutical composition (Poria cocos 5g, red peony root 5g, Dangshen 5g, fried atractylodes 5g, Angelica 5g, Chuanxiong 5g, Cassia twig 5g, prepared rehmannia 5g, deer horn 5g, Chuan Niu Xi 5g and dried tangerine peel 5g) twice a day, one dose a day, oral twice a day, for 3 months. The patient's double hip joint pain symptoms disappeared, and the hip joint moved freely.

[0115] Experimental example 3:

[0116] Liu: male, 37 years old, due to long-term heavy drinking caused right hip joint pain, aggravated after activity, after examination diagnosis: right femoral head necrosis (II stage c). Take the water decoction of the pharmaceutical composition (Poria cocos 3g, red peony root 30g, Dangshen 5g, fried atractylodes 5g, Angelica 30g, Chuanxiong 15g, Cassia twig 14g, prepared rehmannia 15g, deer horn 30g, Chuan Niu Xi 30g and dried tangerine peel 10g) twice a day, for 3 months, no obvious right hip joint pain, joint activity is normal. After treatment, 1 year follow-up, no joint pain symptoms, joint activity is normal.

[0117] Experimental example 4:

[0118] Patient: Wang, male, due to "double hip joint pain with limited activity for more than 8 months" for treatment, the patient due to intermittent use of glucocorticoids for tonsillitis, after examination diagnosis: bilateral femoral head necrosis (left II stage c, right II stage b), take the water decoction of the pharmaceutical composition (Poria cocos 28g, red peony root 5g, Dangshen 29g, fried atractylodes 30g, Angelica 5g, Chuanxiong 30g, Cassia twig 30g, prepared rehmannia 29g, deer horn 30g, Chuan Niu Xi 28g and dried tangerine peel 30g) a day, oral twice a day, for 3 months, no obvious pain symptoms in double hip joint, joint activity is normal. 12 months after follow-up, the patient's double hip joint moves normally, and has no pain and discomfort symptoms.

[0119] Experimental example 5:

[0120] Xu, male, 20 years old, bilateral hip joint pain for more than 2 months, the patient has had psoriasis for 3 years, and has taken oral and external use of glucocorticoids. Physical examination shows that the bilateral greater trochanter posterior pressure pain is (+), the left hip joint flexion is 120°, and the right hip joint flexion is 110°. VAS score is 6. Diagnosis: bilateral femoral head necrosis (left III stage a, right III stage a). Take the medicinal composition (Poria cocos 14g, red peony root 6g, radix codonopsis 27g, fried atractylodes 17g, angelica 7g, chuanxiong 29g, cassia twig 28g, prepared rehmannia 8g, deer horn 26g, chuan niu xi 15g and dried tangerine peel 18g) decoction, one dose per day, taken orally twice a day, for 3 months. The patient has no obvious pain in the bilateral hip joints, the bilateral hip joint flexion is 130°, and the VAS score is 2. After 2 years of follow-up after treatment, the patient has no special discomfort in the bilateral hip joints.

[0121] Experimental Example 6:

[0122] Guo, male, 53 years old, bilateral hip joint pain for more than 1 year, especially on the left side, the patient has a history of alcohol consumption for more than 40 years. Physical examination shows that the bilateral hip joint pressure pain is (+), the left hip joint flexion is 100°, the right hip joint flexion is 120°, and the VAS score is 6. Combined with the examination of bilateral hip nucleus, CT and X-ray film, the diagnosis is bilateral femoral head necrosis (left II stage c, right II stage b). Take the medicinal composition (Poria cocos 20g, red peony root 24g, radix codonopsis 20g, fried atractylodes 26g, angelica 19g, chuanxiong 9g, cassia twig 21g, prepared rehmannia 20g, deer horn 18g, chuan niu xi 19g and dried tangerine peel 27g) decoction, one dose per day, taken orally twice a day, for 3 months. There is no obvious pain in the bilateral hip joints, the VAS score is 2, and the bilateral hip joint flexion is 130°.

[0123] Experimental Example 7:

[0124] Chen, male, 58 years old, bilateral hip joint pain with limited activity for more than 4 months, especially on the right side, the patient has no history of hormone use, no history of hip trauma, and denies alcohol consumption history. Physical examination shows that the bilateral inguinal midpoint and greater trochanter pressure pain is (+), the left hip joint flexion is 110°, the right hip joint flexion is 100°, and the VAS score is 6. Diagnosis: bilateral femoral head necrosis (left III stage a, right II stage c). Take the medicinal composition (Poria cocos 25g, red peony root 4g, radix codonopsis 8g, fried atractylodes 6g, angelica 24g, chuanxiong 19g, cassia twig 27g, prepared rehmannia 26g, deer horn 3g, chuan niu xi 7g and dried tangerine peel 15g) decoction, one dose per day, taken orally twice a day, for 3 months. The patient has no obvious pain in the bilateral hip joints, the bilateral hip joint flexion is 120°, and the liver and kidney function test results are normal. The patient has no special discomfort after 13 months of follow-up after treatment.

[0125] Experimental Example 8:

[0126] Hao, female, 32 years old, right hip pain for more than 10 days, the patient because of tubal obstruction, using dexamethasone tubal hydrotubation 7 months. Physical examination: right inguinal midpoint and greater trochanter tenderness (+), no obvious tenderness around the left hip joint, left hip flexion 130°, right hip flexion 120°, VAS score 5. Combined with double hip joint MRI, CT and X-ray examination, diagnosis: bilateral femoral head necrosis (left II period c, right II period b) take the water decoction of the pharmaceutical composition (Poria cocos 15g, red peony root 12g, Dangshen 15g, fried atractylodes 15g, Angelica 12g, Chuanxiong 12g, Ramulus Cinnamomi 12g, Radix Rehmanniae Preparata 15g, Cornu Cervi Pantotrichum 10g, Chuan Niu Xi 15g and Pericarpium Citri Reticulatae 12g), one dose per day, oral twice, for three months. The patient has no obvious pain in both hip joints, VAS score 2, and the flexion of both hip joints is 130°. 6 months follow-up, the patient has no special discomfort in both hip joints.

[0127] Finally, it should be noted that: the above examples are used to illustrate the technical solutions of the present application, but not to limit them; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that: it can still modify the technical solutions recorded in the foregoing examples, or make equivalent replacement for part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A pharmaceutical composition for treating avascular necrosis of the femoral head, characterized in that, It is made from the following ingredients in the indicated weight proportions: 5 parts Poria cocos, 5 parts Paeonia lactiflora, 5 parts Codonopsis pilosula, 5 parts stir-fried Atractylodes macrocephala, 5 parts Angelica sinensis, 5 parts Ligusticum chuanxiong, 5 parts Cinnamomum cassia, 5 parts Rehmannia glutinosa, 5 parts deer antler, 5 parts Achyranthes bidentata, and 5 parts Citrus reticulata peel.

2. The method for preparing the pharmaceutical composition according to claim 1, characterized in that, Includes the following steps: ① Add 11-13 times the amount of water to Poria cocos, Paeonia lactiflora, Codonopsis pilosula, stir-fried Atractylodes macrocephala, Angelica sinensis, Ligusticum chuanxiong, Cinnamomum cassia, Rehmannia glutinosa, Achyranthes bidentata, Citrus reticulata peel and deer antler, decoct for 1.2-1.8 hours to obtain decoction, separate the decoction to obtain medicinal liquid and dregs, and concentrate the medicinal liquid to obtain concentrated liquid; ② Add 9-11 times the amount of water to the dregs obtained in step ① and decoct for 1.2-1.8 hours to obtain decoction. Separate the decoction to obtain medicinal liquid and dregs. Combine the medicinal liquid with the concentrated liquid in step ① and continue to concentrate to obtain concentrated liquid. ③ Add 9-11 times the amount of water to the dregs obtained in step ② and decoct for 1.2-1.8 hours to obtain the decoction. Separate the decoction to obtain the liquid and dregs. Combine the liquid with the concentrated liquid from steps ① and ② and continue to concentrate to obtain the final concentrated liquid. ④ The final concentrate obtained in step ③ is dried under reduced pressure, pulverized, and then the dry paste is further processed to obtain dry paste powder.

3. The method for preparing the pharmaceutical composition according to claim 2, characterized in that, The method for separating the decoction liquid in steps ①-③ is filtration.

4. A method for preparing the pharmaceutical composition according to claim 2 or 3, characterized in that, In step ④, the powder is pulverized and then sieved to obtain a dry paste.

5. The method for preparing the pharmaceutical composition according to claim 2 or 3, characterized in that, The concentration method in step ① is to concentrate the drug solution to a relative density of 1.10-1.15; The concentration method in step ② is to concentrate the drug solution to a relative density of 1.10-1.15; In step ③, the concentration method is used to concentrate the medicinal solution to a relative density of 1.10-1.

15.

6. The method for preparing the pharmaceutical composition according to claim 5, characterized in that, The concentration temperature in step ① is 60-90℃; And / or, the concentration temperature in step ② is 60-90℃; And / or, the concentration temperature in step ③ is 60-90℃.

7. The method for preparing the pharmaceutical composition according to claim 2 or 3, characterized in that, The specific gravity of the final concentrate in step ③ is 1.10 g / cm³. 3 .

8. The method for preparing the pharmaceutical composition according to claim 2 or 3, characterized in that, The temperature for vacuum drying in step ④ is 60-90℃.

9. The method for preparing the pharmaceutical composition according to claim 2 or 3, characterized in that, It also includes step ⑤: mixing the dry powder obtained in step ④ with dextrin until homogeneous, and then dry-pressing it into granules.

10. The method for preparing the pharmaceutical composition according to claim 9, characterized in that, Step ⑤ also includes: granulation through sieves No. 1 and No. 5, combining the particles that do not pass through sieve No. 1 with the fine powder that passes through sieve No. 5 and re-pressing them into granules to obtain drug granules.

11. A drug for treating avascular necrosis of the femoral head, characterized in that, Includes the pharmaceutical composition of claim 1, or the pharmaceutical composition prepared by any one of the preparation methods of claims 2-10.

12. The medicament for treating avascular necrosis of the femoral head according to claim 11, characterized in that, The drug is an oral formulation.

13. The medicament for treating avascular necrosis of the femoral head according to claim 12, characterized in that, The oral preparations include granules, decoctions, tablets, powders, ointments, pills, capsules, or oral liquids.

14. The use of the pharmaceutical composition of claim 1, or the medicament of any one of claims 11-13, in the preparation of any of the following medicaments: 1) Medications to regulate blood lipids in patients with avascular necrosis of the femoral head; 2) Medications that promote bone repair; 3) Medications to improve hip joint function.

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