Composition for treating femoral head necrosis, preparation method and application

Abstract

The invention provides a composition for treating femoral head necrosis, a preparation method and application, and relates to the field of pharmaceutical compositions.The preparation method of the composition comprises the steps that 1, lycopodium clavatum, rhizoma sparganii and green pericarpium citri reticulatae are smashed and sieved according to the formula amount, and fine powder is obtained; step 2, carrying out alcohol extraction and solid-liquid separation on the prepared rhizoma atractylodis, gentiana macrophylla, Chinese starjasmine stem and prepared stiff silkworm according to the formula ratio to obtain an alcohol extract; step 3, performing water extraction on the stephania tetrandra, the radix cyathulae, the notopterygium root, the curcuma zedoary, the rice sprout, the malt and the herba epimedii according to the formula amount, and performing solid-liquid separation to obtain a water extract; and 4, mixing the alcohol extract obtained in the step 2, the water extract obtained in the step 3 and the fine powder obtained in the step 1, and drying to obtain the composition. Experiments show that compared with the prior art, the composition can remarkably improve blood viscosity and bone metabolism level, improve the treatment effect on steroid-induced femoral head necrosis and meet clinical application requirements.

Description

Technical Field

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

[0002] Femoral head necrosis is a pathological evolution process, which initially occurs in the weight-bearing area of ​​the femoral head. Under the action of stress, the trabecular structure of the necrotic bone is damaged, namely microfracture and the subsequent repair process of the damaged bone tissue. There are two causes of the disease. One is the healing of poorly reduced femoral neck fractures, and the other is the bone tissue's own lesions. At present, the treatments for femoral head necrosis include drug therapy or surgery. In comparison, drug therapy has higher patient compliance, greater universality and easier adjustment, so it is widely accepted. Among them, traditional Chinese medicine treatment of femoral head necrosis is safer and has fewer side effects.

[0003] Patent CN115364187A discloses a Chinese medicine composition for treating femoral head necrosis and its application. The Chinese medicine composition in the invention is made of the following raw materials in the following weight proportions: 15-30g raw astragalus, 10-15g processed atractylodes, 10-20g Stephania tetrandra, 10-15g Cyathula capitata, 10-15g Notopterygium wilfordii, 10-15g Gentiana macrophylla, 10-15g Trachelospermum officinale, 10-15g processed Bombyx batryticatus, 10-15g Lycopodiella cuneata, 10-20g Trillium, 10-20g Curcuma, 5-15g each of green tangerine peel, 10-20g malt, 10-20g malt, and 10-20g Epimedium. The Chinese medicine composition has little side effects. Clinical trials and animal tests have shown that it can reduce the area of ​​necrosis and edema, improve blood, and reduce the incidence of surgery, so that patients can have a chance to avoid the pain of surgery and the pressure of high surgical fees. It has obvious efficacy, is safe and effective, and can be widely used in clinical practice.

[0004] However, the Chinese medicine composition of the above patent is prepared by conventional decoction method, and the active ingredients are lost more. Therefore, the therapeutic effect of the Chinese medicine composition for femoral head necrosis still has room for further improvement. In view of the problems existing in the prior art, it is necessary to find a composition, preparation method and application for treating femoral head necrosis with excellent effect. Summary of the invention

[0005] The present invention aims at the problems existing in the prior art, and provides a composition, preparation method and application for treating femoral head necrosis. The composition is prepared by improving the preparation process on the basis of the prior art. Experiments have found that the composition can significantly improve the therapeutic effect on femoral head necrosis and meet the clinical application needs.

[0006] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] In a first aspect, the present invention provides a method for preparing a composition for treating femoral head necrosis, the composition comprising raw astragalus, processed atractylodes, tetrandra, cyathula officinalis, notopterygium wilfordii, gentiana macrophylla, trachelospermum officinale, processed bombyx batryticatus, herba striatae, zedoariae curcumae, green tangerine peel, malt, malt and epimedium, and the preparation method comprises the following steps:

[0008] Step 1, crush and sieve the formulated amount of Herba Lycopodii, Herba Tripterygii and Pericarpium Citri Reticulatae to obtain fine powder;

[0009] Step 2, extracting the prepared Atractylodes lancea, Gentiana macrophylla, Trachelospermi schrenkiana and Bombyx batryticatus in the formulated amounts by alcohol, separating the solid from the liquid, and obtaining an alcohol extract;

[0010] Step 3, extracting the formulated amount of Radix Stephaniae Tetrandrae, Rhizoma Cyathulae, Rhizoma Notopterygii, Rhizoma Curcumae, Rhizoma Amaranthus, Rhizoma Malt and Rhizoma Epimedii with water, separating the solid from the liquid, and obtaining a water extract;

[0011] Step 4: Mix the alcohol extract obtained in step 2, the water extract obtained in step 3 and the fine powder obtained in step 1, and dry them to obtain the composition.

[0012] In some embodiments, the sieving in step 1 is through a 80-100 mesh sieve.

[0013] In some embodiments, the solvent for the alcohol extraction in step 2 is ethanol. Preferably, the volume fraction of the ethanol is 80-95%, and more preferably 85-90%.

[0014] In some embodiments, the amount of alcohol added in step 2 is 8-12 times, preferably 10 times, the total amount of processed Atractylodes lancea, Gentiana macrophylla, Trachelospermi Caulis and processed Bombyx Batryticatus.

[0015] In some embodiments, the conditions for the alcohol extraction in step 2 are: temperature 65-80°C, alcohol extraction 1-5 times, each time 0.5-2h; preferably 70-75°C, alcohol extraction 1-3 times, each time 1h.

[0016] In some embodiments, the amount of water added in step 3 is 6-15 times, preferably 10 times, the total amount of Stephania tetrandra, Rhizoma Cyathulae, Rhizoma Notopterygii, Rhizoma Curcumae, Germinatus, Malt and Herba Epimedii.

[0017] In some embodiments, the conditions for water extraction in step 3 are: temperature 85-95° C., water extraction 1-3 times, each time 1-3 hours, preferably 90° C., water extraction 2 times, each time 2 hours.

[0018] In some embodiments, the drying in step 4 is low-temperature drying, the drying temperature is 50-70° C., and the vacuum degree is -0.04 to -0.02P.

[0019] The solid-liquid separation in the present invention is a conventional solid-liquid separation technique in the art, such as centrifugation, filtration, etc.

[0020] In a second aspect, the present invention provides a composition for treating femoral head necrosis, which is prepared by the above-mentioned preparation method.

[0021] In some embodiments, the composition comprises, by weight, 15-30 parts of raw astragalus, 10-15 parts of processed atractylodes, 10-20 parts of tetrandra, 10-15 parts of cyathula, 10-15 parts of notopterygium, 10-15 parts of gentiana macrophylla, 10-20 parts of trachelospermum officinale, 10-15 parts of processed bombyx batryticatus, 10-15 parts of lycopodii herba, 10-20 parts of trifoliate lanceolate, 10-20 parts of curcuma, 5-15 parts of green tangerine peel, 10-20 parts of malt, 10-20 parts of malt, and 10-20 parts of epimedium;

[0022] Preferably, the ingredients include 30 parts of raw astragalus, 12 parts of processed atractylodes, 15 parts of tetrandragonae, 12 parts of cyathulae, 12 parts of notopterygium, 12 parts of gentiana macrophylla, 15 parts of trachelospermum officinale, 10 parts of processed bombyx batryticatus, 12 parts of lycopodii herba, 15 parts of sparganium, 15 parts of curcuma, 9 parts of green tangerine peel, 12 parts of malt, 12 parts of malt and 15 parts of epimedium.

[0023] In a third aspect, the present invention provides the use of the composition prepared by the aforementioned preparation method in the preparation of a drug for treating femoral head necrosis.

[0024] In some embodiments, the femoral head necrosis is alcoholic femoral head necrosis or steroid-induced femoral head necrosis.

[0025] In some embodiments, the femoral head necrosis includes stage I, stage II, and stage III.

[0026] In a fourth aspect, the present invention provides a drug for treating femoral head necrosis, comprising a composition prepared by the aforementioned preparation method and pharmaceutically acceptable excipients.

[0027] In some embodiments, the dosage form of the drug includes decoction, pill, tablet, mixture, capsule, granule, powder, paste or wine.

[0028] The technical effects achieved by the present invention are:

[0029] The present invention is prepared by improving the preparation process on the basis of the prior art, using alcohol extraction of processed Atractylodes lancea, Gentiana macrophylla, Trachelospermi schrenkiana and processed Bombyx batryticatus, water extraction of Radix Stephaniae tetrandrae, Rhizoma Cyathulae, Radix Notopterygii, Rhizoma Curcumae, malt, malt and Herba Epimedii, and in the co-extraction process of different medicinal flavors, interactions or influences may occur to promote the dissolution of active ingredients, and then the extracts prepared by different extraction processes are compounded to enhance the efficacy and promote the therapeutic effect. Experiments have found that compared with the prior art, the composition of the present invention can significantly improve blood viscosity and bone metabolism levels, enhance the therapeutic effect of hormone-induced femoral head necrosis, and meet clinical application needs.

[0030] Experiments have found that when smilax china, trifoliate green tangerine peel and green tangerine peel are co-extracted with other medicinal ingredients, it is not conducive to enhancing the efficacy of the extract, thus affecting the therapeutic effect. DETAILED DESCRIPTION

[0031] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0032] Before further describing the specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the examples of the present invention are for describing specific embodiments rather than for limiting the scope of protection of the present invention.

[0033] When the embodiment gives a numerical range, it should be understood that, unless otherwise specified in the present invention, the two endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those of ordinary skill in the art to which the present invention belongs.

[0034] The "drug" described in the present invention includes the aforementioned composition and pharmaceutically acceptable excipients. In a specific embodiment, the composition described in the present invention is provided in the drug in an effective amount (eg, a therapeutically effective amount).

[0035] The "pharmaceutically acceptable excipients" described in the present invention include inert diluents, dispersants and / or granulating agents, surfactants and / or emulsifiers, disintegrants, binders, preservatives, buffers, lubricants. Excipients (such as cocoa butter), colorants, coating agents, sweeteners, flavoring agents and aromatics may also be present in the pharmaceutical composition.

[0036] The "medicament" described in the present invention can be prepared by any method known in pharmacy. Generally speaking, these preparation methods include associating the aforementioned composition (i.e., the first active ingredient) with a carrier or excipient and / or one or more other auxiliary ingredients, and then if necessary and / or desired, shaping and / or packaging the product into a desired single dose or multiple dose unit.

[0037] The drug of the present invention can be prepared according to known methods, such as the methods described in the general rules for preparation of the Chinese Pharmacopoeia 2020, the Japanese Pharmacopoeia 16th edition, the United States Pharmacopoeia and the European Pharmacopoeia 9th edition. The specific preparation method depends on the dosage form.

[0038] The first active ingredient and pharmaceutically acceptable excipients in the "medicament" of the present invention will vary according to the identity, body shape and / or condition of the subject to be treated and further according to the route of administration of the composition. The medicament may contain between 0.1% and 100% (w / w) of the first active ingredient.

[0039] "Treatment" as used herein, unless otherwise indicated, means reversing, alleviating, inhibiting the progression of, or preventing the condition or disorder or one or more symptoms of such condition or disorder to which the term applies, unless otherwise indicated. The term "treat" as used herein refers to the act of treating, as "treat" is defined immediately above.

[0040] The "effective amount" described in the present invention refers to an amount sufficient to induce a desired biological response. The effective amount of the active ingredients of the present invention may vary depending on factors such as the desired biological endpoint, the pharmacokinetics of the compound, the condition being treated, the mode of administration, and the age and health of the subject. In certain embodiments, the effective amount is a therapeutically effective amount. The effective amount is the amount of the first active ingredient described in the present invention in a single dose. In certain embodiments, the effective amount is the combined amount of the active ingredients described in the present invention in multiple doses.

[0041] The "therapeutically effective amount" described in the present invention is an amount sufficient to provide a therapeutic benefit in the treatment of a disorder or sufficient to delay or minimize one or more symptoms associated with the disorder. The therapeutically effective amount of a composition means an amount of a therapeutic agent that provides a therapeutic benefit in the treatment of a disorder alone or in combination with other therapies. The term "therapeutically effective amount" can encompass an amount that improves overall therapy, reduces or avoids symptoms, signs or causes of a disorder, and / or enhances the therapeutic efficacy of another therapeutic agent. In certain embodiments, a therapeutically effective amount is an amount sufficient to treat any disease or disorder described.

[0042] The terms "subject" or "patient" as used in the present invention are well known in the art and are used interchangeably herein to refer to mammals, including dogs, cats, rats, mice, monkeys, cows, horses, goats, sheep, pigs, camels, and most preferably humans. The term does not denote a particular age or sex. Thus, both adult and newborn subjects, whether male or female, are encompassed.

[0043] It is worth noting that the raw materials used in the present invention are all common commercially available products, so their sources are not specifically limited.

[0044] Embodiment 1 Composition for treating femoral head necrosis

[0045] The prescription of the composition (by weight) is:

[0046] 30 parts of raw Astragalus, 12 parts of processed Atractylodes, 15 parts of Stephania tetrandra, 12 parts of Cyathula officinalis, 12 parts of Notopterygium wilfordii, 12 parts of Gentiana macrophylla, 15 parts of Trachelospermi spatholobi, 10 parts of processed Bombyx batryticatus, 12 parts of Lycopodiella cuneata, 15 parts of Tripterygium wilfordii, 15 parts of Curcuma zedoaria, 9 parts of Citrus reticulatae, 12 parts of malt, 12 parts of malt and 15 parts of Epimedium;

[0047] The specific preparation method is:

[0048] Step 1, crush the formulated amount of Herba Lycopodii, Herba Tripterygii and Pericarpium Citri Reticulatae through a 100-mesh sieve to obtain fine powder for later use;

[0049] Step 2, mix the prepared Atractylodes lancea, Gentiana macrophylla, Trachelospermi schrenkiana and prepared Bombyx batryticatus in the prescribed amount, add 10 times the amount of 90% ethanol, extract at 70° C. for 3 times, each time for 1 hour, centrifuge, combine the filtrate, and obtain an alcohol extract;

[0050] Step 3, mix the formula amount of Hanfangji, Chuanxiong, Qianghuo, Curcuma, malt, malt and epimedium, add 10 times of water, extract twice at a temperature of 90°C, each time for 2 hours, centrifuge, combine the filtrate, and obtain a water extract;

[0051] Step 4: Mix the alcohol extract obtained in step 2, the water extract obtained in step 3 and the fine powder obtained in step 1, and dry them at low temperature (temperature 60° C., vacuum degree -0.03P) to obtain the composition.

[0052] Embodiment 2 Composition for treating femoral head necrosis

[0053] The prescription of the composition (by weight) is:

[0054] 15 parts of raw astragalus, 10 parts of processed atractylodes, 10 parts of tetrandra, 10 parts of cyathula, 10 parts of notopterygium, 10 parts of gentiana, 10 parts of trachelospermum, 10 parts of processed bombyx batryticatus, 10 parts of lycopodii herba, 10 parts of trifoliate lanceolate, 10 parts of curcuma, 5 parts of green tangerine peel, 10 parts of malt, 10 parts of malt and 10 parts of epimedium;

[0055] The specific preparation method is:

[0056] Step 1, crush the formulated amount of Herba Lycopodii, Herba Tripterygii and Pericarpium Citri Reticulatae through a 100-mesh sieve to obtain fine powder for later use;

[0057] Step 2, mix the prepared Atractylodes lancea, Gentiana macrophylla, Trachelospermi Caulis and prepared Bombyx batryticatus in the prescribed amount, add 8 times the amount of 95% ethanol, extract at 80° C. for 3 times, each time for 0.5 h, centrifuge, combine the filtrate, and obtain an alcohol extract;

[0058] Step 3, mix the formula amount of Hanfangji, Chuanxiong, Qianghuo, Curcuma, malt, malt and epimedium, add 6 times of water, extract twice at a temperature of 95°C, each time for 1 hour, centrifuge, combine the filtrate, and obtain a water extract;

[0059] Step 4: Mix the alcohol extract obtained in step 2, the water extract obtained in step 3 and the fine powder obtained in step 1, and dry them at low temperature (temperature 60° C., vacuum degree -0.03P) to obtain the composition.

[0060] Example 3 Composition for treating femoral head necrosis

[0061] The prescription of the composition (by weight) is:

[0062] 30 parts of raw astragalus, 15 parts of processed atractylodes, 20 parts of tetrandra, 15 parts of cyathula, 15 parts of notopterygium, 15 parts of gentiana macrophylla, 20 parts of trachelospermum officinale, 15 parts of processed bombyx batryticatus, 15 parts of lycopodii herba, 20 parts of sparganium, 20 parts of curcuma, 15 parts of green tangerine peel, 20 parts of malt, 20 parts of malt and 20 parts of epimedium;

[0063] The specific preparation method is:

[0064] Step 1, crush the formulated amount of Herba Lycopodii, Herba Tripterygii and Pericarpium Citri Reticulatae through a 100-mesh sieve to obtain fine powder for later use;

[0065] Step 2, mix the prepared Atractylodes lancea, Gentiana macrophylla, Trachelospermi schrenkiana and prepared Bombyx batryticatus in the prescribed amount, add 12 times the amount of 80% ethanol, extract at 65° C. for 3 times, each time for 2 hours, centrifuge, combine the filtrate, and obtain an alcohol extract;

[0066] Step 3, mix the formula amount of Hanfangji, Chuanxiong, Qianghuo, Curcuma, malt, malt and epimedium, add 15 times of water, extract twice at a temperature of 85°C, each time for 3 hours, centrifuge, combine the filtrate, and obtain a water extract;

[0067] Step 4: Mix the alcohol extract obtained in step 2, the water extract obtained in step 3 and the fine powder obtained in step 1, and dry them at low temperature (temperature 60° C., vacuum degree -0.03P) to obtain the composition.

[0068] Comparative Example 1 Composition for treating femoral head necrosis

[0069] The difference between this comparative example and Example 1 is that the preparation method is water extraction.

[0070] The preparation method is:

[0071] Step 1, mix the formula amount of raw astragalus, processed atractylodes, fangji, chuanxiong, qianghuo, qinjiao, trachelospermum officinale, processed bombyx batryticatus, lycopodiella cuneata, sparganium, zedoaria, green tangerine peel, malt, malt and epimedium, add 10 times of water, extract twice at a temperature of 90° C., each time for 2 hours, centrifuge, combine the filtrate to obtain a water extract;

[0072] Step 2: Dry the water extract obtained in step 1 at low temperature (temperature 60° C., vacuum degree -0.03P) to obtain the composition.

[0073] Comparative Example 2 Composition for treating femoral head necrosis

[0074] The difference between this comparative example and Example 1 is that there is no fine powder step in the preparation process.

[0075] The specific preparation method is:

[0076] Step 1, mix the formulated amount of Atractylodes lancea, Gentiana macrophylla, Trachelospermi scabra, Bombyx batryticatus and Herba Lycopodii, add 10 times the amount of 90% ethanol, extract at 70°C for 3 times, each time for 1 hour, centrifuge, combine the filtrate, and obtain an alcohol extract;

[0077] Step 2, mix the formula amount of Hanfangji, Chuanxiong, Qianghuo, Curcuma, Sanleng, Qingchenpi, Guya, Malt and Epimedium, add 10 times of water, extract twice at a temperature of 90°C, each time for 2 hours, centrifuge, combine the filtrate, and obtain a water extract;

[0078] Step 3: Mix the alcohol extract obtained in step 1 and the water extract obtained in step 2, and dry them at low temperature (temperature 60° C., vacuum degree -0.03P) to obtain the composition.

[0079] Comparative Example 3 Composition for treating femoral head necrosis

[0080] The difference between this comparative example and Example 1 is that the steps of fine powder and water extraction in the preparation process are different.

[0081] The specific preparation method is:

[0082] Step 1, crush the formula amount of Stephania tetrandra, Cyathula capitata and Notopterygium wilfordii through a 100-mesh sieve to obtain fine powder for later use;

[0083] Step 2, mix the prepared Atractylodes lancea, Gentiana macrophylla, Trachelospermi schrenkiana and prepared Bombyx batryticatus in the prescribed amount, add 10 times the amount of 90% ethanol, extract at 70° C. for 3 times, each time for 1 hour, centrifuge, combine the filtrate, and obtain an alcohol extract;

[0084] Step 3, mix the formulated amount of Herba Lycopodii, Herba Tripterygii, Herba Citri Reticulatae, Rhizoma Curcumae, Herba Malti, Herba Malti and Herba Epimedii, add 10 times of water, extract twice at 90°C, each time for 2 hours, centrifuge, combine the filtrate, and obtain a water extract;

[0085] Step 4: Mix the alcohol extract obtained in step 2, the water extract obtained in step 3 and the fine powder obtained in step 1, and dry them at low temperature (temperature 60° C., vacuum degree -0.03P) to obtain the composition.

[0086] Effect example: Effect of the composition on femoral head necrosis

[0087] 1. Experimental Animals

[0088] Large white rabbit, weight 2.2-2.8kg.

[0089] 2. Experimental drugs

[0090] The compositions prepared in Examples 1-3 and Comparative Examples 1-3.

[0091] 3. Experimental methods

[0092] The rabbits were injected with prednisolone acetate injection into the buttocks muscle at 12.25 mg / kg each time, once a week for 8 weeks. At the same time, 80,000 u / rabbit of penicillin were injected intramuscularly once a week to prevent infection. After 8 weeks, 3 rabbits were randomly killed, and pathological sections were taken and observed. If unsuccessful, the injection could be continued until all the rabbits randomly selected showed femoral head necrosis, and the model was successfully established (for specific observation methods, please refer to: Li Zhenwei, Experimental study on the effect of sodium danshensu on the number of osteoclasts in rabbit femoral head necrosis [D], master's degree thesis of Zunyi Medical College, 2010).

[0093] The rabbits with successful modeling were randomly divided into a model group, drug-treated groups S1-S3 and D1-D3, and a normal control group, with 8 rabbits in each group.

[0094] The drug administration group was gavaged with the composition provided in the corresponding embodiment or comparative example, with a gavage dose of 2 mg crude drug / kg, and the model combination normal control group was gavaged with an equal volume of normal saline, once a day, for 10 consecutive weeks.

[0095] After the last oral administration, the subjects were fasted but not watered for 12 h, and blood was collected venously to measure the whole blood low shear viscosity (ηbL, mPa·s), whole blood high shear viscosity (ηbH, mPa·s), plasma viscosity (ηP), hematocrit (HCT) and red blood cell aggregation index.

[0096] Before and after treatment, the rabbits were fasted and deprived of water for 12 h, and venous blood was collected. Serum was separated by centrifugation, and serum 25-hydroxyvitamin D [25-(OH)D] levels and N-terminal osteocalcin (N-MID) levels were detected by electrochemiluminescence.

[0097] 4. Experimental results

[0098] 4.1 Effect of composition on blood rheological parameters

[0099] Table 1 Effect of the composition on blood rheological parameters (mean ± standard deviation)

[0100] Group Number ηbL(mPa·s) ηbH(mPa·s) Normal control group 8 27.35±3.17 <![CDATA[4.62±0.18 d ]]> Model Group 8 <![CDATA[58.62±4.20 a ]]> <![CDATA[8.27±0.84 a ]]> Treatment group S1 8 <![CDATA[35.27±2.08 c ]]> <![CDATA[5.07±0.22 c ]]> Treatment group S2 8 <![CDATA[37.56±2.46 c ]]> <![CDATA[5.26±0.30 c ]]> Treatment group S3 8 <![CDATA[36.39±2.19 c ]]> <![CDATA[5.18±0.27 c ]]> Drug group D1 8 <![CDATA[46.36±5.71 b ]]> <![CDATA[6.44±0.35 b ]]> Treatment group D2 8 <![CDATA[47.82±6.63 b ]]> <![CDATA[6.58±0.56 b ]]> Drug group D3 8 <![CDATA[45.92±6.08 b ]]> <![CDATA[6.39±0.45 b ]]>

[0101] Note: Different letters in the same column indicate significant differences among the groups, P < 0.05.

[0102] As shown in Table 1, compared with the normal group, the whole blood low shear viscosity and whole blood high shear viscosity of the rabbits in the model group were significantly increased (P < 0.05), indicating that the blood viscosity of the rabbits increased and the blood circulation became worse after modeling.

[0103] Compared with the module group, the whole blood low shear viscosity and whole blood high shear viscosity of the rabbits in the drug administration groups S1-S3 were significantly reduced (P < 0.05), indicating that the composition provided in Examples 1-3 can reduce blood viscosity and improve blood circulation.

[0104] Comparison of the administration groups S1-S3 and the administration group D1 shows that, compared with the prior art, the composition prepared by the improved preparation method of the present invention has a significantly improved effect of improving blood circulation (P<0.05).

[0105] By comparing the administration group S1 and the administration groups D1-D2, it can be seen that the effect of the composition prepared in comparative example 2 on improving blood circulation is basically the same as that of D1, with no statistical difference (P>0.05), while the composition prepared in Example 1 is significantly better than comparative examples 1 and 2 in improving blood circulation (P<0.05), indicating that in the technical scheme claimed for protection of the present invention, when Herba Lycopodii, Scutellariae and Citrus reticulatae are co-extracted with other medicinal flavors, it is not conducive to enhancing the efficacy of the extract, thereby affecting the therapeutic effect.

[0106] 4.2 Effect of the composition on bone metabolism

[0107] Table 2 Effect of the composition on bone metabolism level (mean ± standard deviation)

[0108] Number 25-(OH)D (mmol / L) N-MI (μg / L) Normal control group 8 <![CDATA[36.19±4.13 a ]]> <![CDATA[22.83±4.37 d ]]> Model Group 8 <![CDATA[15.65±2.34 d ]]> <![CDATA[56.79±11.34 a ]]> Treatment group S1 8 <![CDATA[26.53±2.08 b ]]> <![CDATA[32.07±6.70 c ]]> Treatment group S2 8 <![CDATA[25.76±2.32 b ]]> <![CDATA[33.84±6.61 c ]]> Treatment group S3 8 <![CDATA[26.01±2.16 b ]]> <![CDATA[32.99±6.34 c ]]> Drug group D1 8 <![CDATA[19.54±1.68 c ]]> <![CDATA[46.38±8.27 b ]]> Treatment group D2 8 <![CDATA[18.68±1.56 c ]]> <![CDATA[47.52±8.52 b ]]> Drug group D3 8 <![CDATA[20.16±1.83 c ]]> <![CDATA[45.13±7.39 b ]]>

[0109] Note: Different letters in the same column indicate significant differences among the groups, P < 0.05.

[0110] As shown in Table 2, compared with the normal group, the 25-hydroxyvitamin D level of rabbits in the model group was significantly decreased (P < 0.05), and the N-terminal osteocalcin level was significantly increased (P < 0.05), indicating that the osteoblast activity of rabbits was reduced after modeling.

[0111] Compared with the module group, the 25-hydroxyvitamin D level of rabbits in the drug-treated groups S1-S3 was significantly increased, and the N-terminal osteocalcin level was significantly decreased (P < 0.05), indicating that the composition provided in Examples 1-3 can increase osteoblast activity and improve bone metabolism.

[0112] Comparison of the administration groups S1-S3 and the administration group D1 shows that, compared with the prior art, the composition prepared by the improved preparation method of the present invention has a significantly improved effect on improving the bone metabolism level (P < 0.05).

[0113] By comparing the dosing group S1 and the dosing groups D1-D2, it can be seen that the effect of the composition prepared in comparative example 2 on improving the bone metabolism level is basically the same as that of D1, with no statistical difference (P>0.05), while the composition prepared in Example 1 is significantly better than comparative examples 1 and 2 in improving the bone metabolism level (P<0.05), indicating that in the technical scheme claimed for protection of the present invention, when Herba Lycopodii, Scutellariae and Citrus reticulatae are co-extracted with other medicinal flavors, it is not conducive to the enhancement of the efficacy of the extract, thereby affecting the therapeutic effect.

[0114] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A composition for treating femoral head necrosis, characterized in that: Including raw astragalus, processed atractylodes, stephania tetrandra, cyathula officinalis, notopterygium wilfordii, gentiana macrophylla, trachelospermum officinale, processed bombyx batryticatus, herba striatae, rhizoma curcumae, green tangerine peel, barley sprout, malt and epimedium; The preparation method of the composition comprises the following steps: Step 1, crush and sieve the formulated amount of Herba Lycopodii, Herba Tripterygii and Pericarpium Citri Reticulatae to obtain fine powder; Step 2, extracting the prepared Atractylodes lancea, Gentiana macrophylla, Trachelospermi schrenkiana and Bombyx batryticatus in the formulated amounts by alcohol, separating the solid from the liquid, and obtaining an alcohol extract; Step 3, extracting the formulated amount of Radix Stephaniae Tetrandrae, Rhizoma Cyathulae, Rhizoma Notopterygii, Rhizoma Curcumae, Rhizoma Amaranthus, Rhizoma Malt and Rhizoma Epimedii with water, separating the solid from the liquid, and obtaining a water extract; Step 4: Mix the alcohol extract obtained in step 2, the water extract obtained in step 3 and the fine powder obtained in step 1, and dry them to obtain the composition.

2. The composition according to claim 1, characterized in that: The sieving in step 1 is through a 80-100 mesh sieve.

3. The composition according to claim 1, characterized in that: The amount of alcohol added in step 2 is 8-12 times the total amount of processed Atractylodes lancea, Gentiana macrophylla, Trachelospermi Caulis and processed Bombyx batryticatus; And / or, the conditions of the alcohol extraction are: temperature 65-80°C, alcohol extraction 1-5 times, each time 0.5-2h.

4. The composition according to claim 1, characterized in that: The amount of water added in step 3 is 6-15 times the total amount of Radix Stephaniae Tetrandrae, Radix Cyathulae, Rhizoma Notopterygii, Rhizoma Curcumae, Rhizoma Amaranthus, Rhizoma Malt and Rhizoma Epimedii; And / or, the conditions of water extraction in step 3 are: temperature 85-95° C., water extraction 1-3 times, each time for 1-3 hours.

5. The composition according to any one of claims 1 to 4, characterized in that: By weight, it includes 15-30 parts of raw astragalus, 10-15 parts of processed atractylodes, 10-20 parts of tetrandra, 10-15 parts of cyathula, 10-15 parts of notopterygium, 10-15 parts of gentiana macrophylla, 10-20 parts of trachelospermum officinale, 10-15 parts of processed bombyx batryticatus, 10-15 parts of lycopodii herba, 10-20 parts of trillium, 10-20 parts of curcuma, 5-15 parts of green tangerine peel, 10-20 parts of malt, 10-20 parts of malt and 10-20 parts of epimedium.

6. A method for preparing the composition according to any one of claims 1 to 5, characterized in that: The following steps are involved: Step 1, crush and sieve the formulated amount of Herba Lycopodii, Herba Tripterygii and Pericarpium Citri Reticulatae to obtain fine powder; Step 2, extracting the prepared Atractylodes lancea, Gentiana macrophylla, Trachelospermi schrenkiana and Bombyx batryticatus in the formulated amounts by alcohol, separating the solid from the liquid, and obtaining an alcohol extract; Step 3, extracting the formulated amount of Radix Stephaniae Tetrandrae, Rhizoma Cyathulae, Rhizoma Notopterygii, Rhizoma Curcumae, Rhizoma Amaranthus, Rhizoma Malt and Rhizoma Epimedii with water, separating the solid from the liquid, and obtaining a water extract; Step 4: Mix the alcohol extract obtained in step 2, the water extract obtained in step 3 and the fine powder obtained in step 1, and dry them to obtain the composition.

7. The preparation method according to claim 6, characterized in that: The sieving in step 1 is through a 80-100 mesh sieve; And / or, the conditions of the alcohol extraction in step 2 are: temperature 65-80° C., alcohol extraction 1-5 times, each time 0.5-2 h; And / or, the conditions of water extraction in step 3 are: temperature 85-95° C., water extraction 1-3 times, each time for 1-3 hours.

8. Use of the composition according to any one of claims 1 to 5 or the composition prepared by the preparation method according to any one of claims 6 to 7 in the preparation of a medicament for treating femoral head necrosis.

9. A drug for treating femoral head necrosis, characterized in that: The invention comprises the composition according to any one of claims 1 to 5 or the composition prepared by the preparation method according to any one of claims 6 to 7 and pharmaceutically acceptable excipients.

10. The drug according to claim 9, characterized in that: The dosage form of the medicine includes decoction, pill, tablet, mixture, capsule, granule, powder, paste or wine.