Pharmaceutical composition for treating thrombus as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and relates to a pharmaceutical composition for treating thrombus and a preparation method and application thereof. The pharmaceutical composition is prepared from the following raw materials: astragalus membranaceus, peach kernels, angelica sinensis, ligusticum wallichii, radix paeoniae rubra, leeches and pseudo-ginseng. The preparation method of the pharmaceutical composition comprises the following steps: (1) extracting radix astragali and radix paeoniae rubra to obtain a medicine residue 1 and volatile oil; (2) carrying out alcohol extraction on peach kernels, angelica sinensis and ligusticum wallichii to obtain medicine residues 2 and an alcohol extract; (3) performing water extraction on the medicine residue 1, the medicine residue 2, leech and pseudo-ginseng to obtain a water extract; and (4) combining and concentrating the alcohol extract and the water extract, and adding the volatile oil to obtain the pharmaceutical composition. Through improvement of a preparation process, the traditional Chinese medicine composition is prepared by combining volatile oil of astragalus membranaceus and red peony roots, alcohol extracts of peach kernels, angelica sinensis and ligusticum wallichii and water extracts of medicine residues and leeches and pseudo-ginseng, and experiments prove that compared with the prior art, the traditional Chinese medicine composition has a better curative effect in the aspect of deep venous thrombosis resistance.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and relates to a pharmaceutical composition for treating thrombus, and a preparation method and use thereof. Background Art

[0002] Deep venous thrombosis of the lower extremities, also known as DVT (deep venous thrombosis), refers to the formation of blood clots in the lumen of the vein due to various reasons. With the rapid development of my country's economy and the continuous improvement of people's living standards, the problem of population aging is becoming increasingly serious. The incidence of bone and joint diseases is increasing year by year, especially the incidence of knee osteoarthritis (KOA) in the elderly population. Knee osteoarthritis can cause pain and disability in middle-aged and elderly people, which has a serious adverse effect on the quality of life of patients. Therefore, patients have higher and higher requirements and expectations for improving their quality of life and reducing pain.

[0003] Traditional treatment methods can no longer meet the requirements and expectations of patients in need, which has led to the continuous popularization and promotion of total knee arthroplasty (TKA) as an ultimate treatment in my country. With the widespread development of TKA, the prevention and treatment of its complications have received more and more attention. In addition to post-arthritis infection, knee instability, prosthesis loosening, etc., deep venous thrombosis (DVT) of the lower limbs after TKA has become one of the most serious complications after TKA. Severe DVT can lead to pulmonary embolism (PE) that threatens the patient's life.

[0004] In medicine, DVT belongs to the category of "femoral swelling", "pulse", "congestion and flow", and "swelling". In Huangdi Neijing Suwen, there is a record of "pulse is called numbness", and in Xuezheng Lun, it is recorded that "blood stasis flows... when the blood stasis dissipates, the swelling and pain will disappear by itself". TKA patients are old and have been ill for a long time, with qi and blood deficiency, and bone shattering and tendon rupture during surgery, which damages tendons and veins, and blood coagulation, causing qi and blood disharmony in the limbs, poor circulation, blood stasis, blood stasis, blood stasis, blood reflux obstruction, disharmony between Ying and Wei, inability to retain body fluids, and overflow of body fluids, which gather into dampness, which is the key to the pathogenesis of this disease.

[0005] At present, the measures to prevent DVT after total joint replacement surgery mainly include: (1) basic preventive measures; during the operation, the surgeon should operate gently and avoid damaging the venous wall as much as possible. After the operation, the patient should be asked to raise the affected limb and perform early active functional exercises on the affected limb. (2) Mechanical preventive measures: plantar venous pump (VEP), inter-pneumatic pressure pump (IPC) and gradient compression stockings (GCS). (3) Drug preventive measures: anticoagulants such as rivaroxaban, warfarin, and low molecular weight heparin. At present, there is still controversy over the cost-effectiveness of various drugs. At the same time, the side effects of various anticoagulants cannot be ignored. Most of the literature believes that although preoperative anticoagulation can effectively reduce the occurrence of DVT, bleeding complications cannot be ignored, especially gastrointestinal bleeding, epidural hematoma, retroperitoneal hematoma, etc. (4) Prevention and treatment with traditional Chinese medicine: using traditional Chinese medicine theory to conduct syndrome differentiation and treatment for patients after surgery, using the holistic concept, regulating body functions, dredging meridians, and regulating the circulation of qi and blood, it has a definite therapeutic effect and has fewer side effects on patients, and is increasingly valued.

[0006] CN115581730A discloses a pharmaceutical composition for treating deep vein thrombosis, which is made of the following raw materials in parts by weight: 5-25g of Astragalus, 6-18g of Peach Kernel, 6-18g of Angelica Sinensis, 6-18g of Chuanxiong, 6-18g of Red Peony Root, 2-10g of Leech, and 3-15g of Panax Notoginseng. The invention is formulated based on effective drugs for clinical treatment of TKA, and is used to prevent lower limb DVT after TKA surgery. It is intended to invigorate qi and dredge meridians, activate blood circulation and dredge collaterals. It has a definite effect in clinical application, has no obvious damage to liver and kidney functions, and is economical and safe. At present, the preparation method of the pharmaceutical composition is traditional decoction, and the loss of effective ingredients is relatively large. How to develop a pharmaceutical composition with better therapeutic effect on this basis is currently extremely challenging. Summary of the invention

[0007] The object of the present invention is to provide a pharmaceutical composition for treating thrombosis with better therapeutic effect, and a preparation method and use thereof.

[0008] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0009] In a first aspect, the present invention provides a pharmaceutical composition for treating thrombosis, wherein the raw materials of the pharmaceutical composition are: astragalus, peach kernel, angelica, chuanxiong, red peony root, leech and notoginseng;

[0010] The preparation method of the pharmaceutical composition comprises the following steps:

[0011] (1) extracting Astragalus and Red Peony Root to obtain a medicinal residue 1 and volatile oil;

[0012] (2) extracting peach kernel, angelica sinensis and ligusticum chuanxiong with alcohol to obtain medicinal residue 2 and alcohol extract;

[0013] (3) extracting the medicinal residue 1, the medicinal residue 2, the leech and the Panax notoginseng with water to obtain a water extract;

[0014] (4) The alcohol extract and the water extract are combined and concentrated, and volatile oil is added to obtain the pharmaceutical composition.

[0015] In some embodiments, the extraction in step (1) is steam distillation.

[0016] Preferably, the amount of water added is 4-7 times the mass of Astragalus and Red Peony Root; more preferably, it is 5 times.

[0017] In some embodiments, the alcohol extraction in step (2) is reflux extraction using alcohol as solvent.

[0018] Preferably, the alcohol is at least one of ethanol, propanol, butanol and pentanol; more preferably, it is ethanol.

[0019] Preferably, the volume fraction of the alcohol is 75-90%, more preferably 85%.

[0020] Preferably, the amount of the alcohol used is 6-12 times, preferably 8 times, the total mass of peach kernel, angelica and chuanxiong.

[0021] Preferably, the number of reflux extractions is 1-5 times, more preferably 2-3 times; the time for each reflux extraction is 0.5-3 h, more preferably 1-2 h.

[0022] In some embodiments, the water extraction in step (3) is reflux extraction using water as solvent.

[0023] Preferably, the amount of water used is 8-14 times the total mass of astragalus, peach kernel, angelica, ligusticum chuanxiong, red peony root, leech and notoginseng, preferably 12 times.

[0024] Preferably, the number of reflux extractions is 1-5 times, more preferably 2-3 times; the time for each reflux extraction is 1-3 hours, more preferably 1-2 hours.

[0025] In some embodiments, the concentration in step (4) is concentrated under reduced pressure at a temperature of 50-80° C., preferably 60° C.;

[0026] Preferably, the concentration is to concentrate to a relative density of 1.10-1.12 (60° C.).

[0027] In some embodiments, the raw materials of the pharmaceutical composition are as follows by weight: 5-25g of Astragalus, 6-18g of Peach Kernel, 6-18g of Angelica, 6-18g of Chuanxiong, 6-18g of Red Peony Root, 2-10g of Leech, and 3-15g of Panax Notoginseng.

[0028] In some embodiments, the raw materials of the pharmaceutical composition are as follows by weight: 10-20g of Astragalus, 9-15g of Peach Kernel, 9-15g of Angelica, 9-15g of Chuanxiong, 9-15g of Red Peony Root, 4-8g of Leech, and 6-12g of Panax Notoginseng.

[0029] In some embodiments, the raw materials of the pharmaceutical composition are as follows by weight: 15g of Astragalus, 12g of Peach Kernel, 12g of Angelica, 12g of Ligusticum chuanxiong, 12g of Red Peony Root, 6g of Hirudo, and 9g of Panax Notoginseng.

[0030] In a second aspect, the present invention provides a method for preparing a pharmaceutical composition for treating thrombosis, wherein the raw materials of the pharmaceutical composition are: astragalus, peach kernel, angelica, chuanxiong, red peony root, leech and notoginseng; the method comprises the following steps:

[0031] (1) extracting Astragalus and Red Peony Root to obtain a medicinal residue 1 and volatile oil;

[0032] (2) extracting peach kernel, angelica sinensis and ligusticum chuanxiong with alcohol to obtain medicinal residue 2 and alcohol extract;

[0033] (3) extracting the medicinal residue 1, the medicinal residue 2, the leech and the Panax notoginseng with water to obtain a water extract;

[0034] (4) The alcohol extract and the water extract are combined and concentrated, and volatile oil is added to obtain the pharmaceutical composition.

[0035] In some embodiments, the extraction in step (1) is steam distillation.

[0036] Preferably, the amount of water added is 4-7 times the mass of Astragalus and Red Peony Root; more preferably, it is 5 times.

[0037] In some embodiments, the alcohol extraction in step (2) is reflux extraction using alcohol as solvent.

[0038] Preferably, the alcohol is at least one of ethanol, propanol, butanol and pentanol; more preferably, it is ethanol.

[0039] Preferably, the volume fraction of the alcohol is 75-90%, more preferably 85%.

[0040] Preferably, the amount of the alcohol used is 6-12 times, preferably 8 times, the total mass of peach kernel, angelica and chuanxiong.

[0041] Preferably, the number of reflux extractions is 1-5 times, more preferably 2-3 times; the time for each reflux extraction is 0.5-3 h, more preferably 1-2 h.

[0042] In some embodiments, the water extraction in step (3) is reflux extraction using water as solvent.

[0043] Preferably, the amount of water used is 8-14 times the total mass of astragalus, peach kernel, angelica, ligusticum chuanxiong, red peony root, leech and notoginseng, preferably 12 times.

[0044] Preferably, the number of reflux extractions is 1-5 times, more preferably 2-3 times; the time for each reflux extraction is 1-3 hours, more preferably 1-2 hours.

[0045] In some embodiments, the concentration in step (4) is concentrated under reduced pressure at a temperature of 50-80° C., preferably 60° C.;

[0046] Preferably, the concentration is to concentrate to a relative density of 1.10-1.12 (60° C.).

[0047] In a third aspect, the present invention provides use of the aforementioned pharmaceutical composition in the preparation of a drug for treating thrombosis.

[0048] In a fourth aspect, the present invention provides a drug for treating thrombosis, comprising the aforementioned pharmaceutical composition and pharmaceutically acceptable excipients.

[0049] The dosage form of the medicine in the present invention is capsule, granule, tablet, mixture or syrup.

[0050] Compared with the prior art, the present invention has the following beneficial effects:

[0051] The pharmaceutical composition of the present invention is prepared by improving the preparation process, extracting volatile oils from astragalus and red peony root, and combining the volatile oils from astragalus and red peony root, the alcohol extracts from peach kernel, angelica and ligusticum chuanxiong, and the water extracts from the above-mentioned medicinal residues and leeches and notoginseng. Experiments have shown that compared with the prior art, the present invention has better therapeutic effect in preventing deep vein thrombosis.

[0052] During the experiment, it was found that changes in the extraction process had a significant impact on the efficacy of the drug, resulting in significant differences in the anti-thrombotic properties of the prepared drug composition. DETAILED DESCRIPTION

[0053] The present invention is described below through specific embodiments to make the technical solution of the present invention easier to understand and grasp, but the present invention is not limited thereto, and the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments.

[0054] The endpoints and any value of the scope disclosed in this article are not limited to the accurate scope or value, and these scopes or values ​​should be understood to include values ​​close to these scopes or values. For numerical ranges, between the endpoint values ​​of each scope, between the endpoint values ​​of each scope and a separate point value, and between separate point values, one or more new numerical ranges can be combined with each other, and these numerical ranges should be considered as specifically disclosed in this article. Unless the context clearly indicates otherwise, the singular form "one", "a kind of" and "described" as used herein include singular and plural indicators. The numerical range described by the endpoint is included in all numerical values ​​and fractions within the corresponding range, as well as the described endpoint.

[0055] The "drug" described in the present invention comprises the aforementioned pharmaceutical composition or the aforementioned Chinese herbal extract and pharmaceutically acceptable excipients. In a specific embodiment, the pharmaceutical composition or the aforementioned Chinese herbal extract described in the present invention is provided in the drug in an effective amount (e.g., a therapeutically effective amount).

[0056] 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.

[0057] The "drug" described in the present invention can be prepared by any method known in pharmacy. Generally speaking, these preparation methods include associating the aforementioned pharmaceutical 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.

[0058] 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. It depends on the dosage form.

[0059] 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.

[0060] "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.

[0061] 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.

[0062] 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 pharmaceutical 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" may 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.

[0063] 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, mice, 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.

[0064] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention. The experimental methods described in the following embodiments are conventional methods unless otherwise specified; the reagents and materials can be obtained from commercial channels unless otherwise specified. It is worth noting that the temperature of ethanol extraction in this embodiment is 60-70°C, and the temperature of water extraction is 85-90°C.

[0065] Example 1 Preparation of pharmaceutical composition

[0066] The prescription of the pharmaceutical composition is: 25g of Astragalus, 18g of Peach Kernel, 18g of Angelica, 18g of Chuanxiong, 18g of Red Peony Root, 10g of Leech, and 15g of Panax Notoginseng.

[0067] The preparation method is:

[0068] (1) Mix the astragalus and red peony root in the formula amount, add 4 times the amount of water and perform steam distillation for 3 hours to obtain a medicinal residue 1 and volatile oil;

[0069] (2) Mix the formulated amount of peach kernel, angelica and chuanxiong, add 12 times the amount of 75% ethanol and extract for 3 times, each time for 3 hours, combine the filtrates, and obtain the alcohol extract and the residue 2;

[0070] (3) mixing the residue 1 obtained in step (1) and the residue 2 obtained in step (2) with the formulated amount of leech and Panax notoginseng, adding 8 times the amount of water and refluxing and extracting for 3 times, each time for 1 hour, combining the filtrates to obtain a water extract;

[0071] (4) The alcohol extract obtained in step (2) and the water extract obtained in step (3) are combined, concentrated under reduced pressure at 60° C. to a relative density of 1.10-1.12 (60° C.), and the volatile oil obtained in step (1) is added to obtain the pharmaceutical composition.

[0072] Example 2 Preparation of pharmaceutical composition

[0073] The prescription of the pharmaceutical composition is: 5g of Astragalus, 6g of Peach Kernel, 6g of Angelica, 6g of Chuanxiong, 6g of Red Peony Root, 2g of Leech, and 3g of Panax Notoginseng.

[0074] The preparation method is:

[0075] (1) Mix the astragalus and red peony root in the formula amount, add 7 times the amount of water and perform steam distillation for 3 hours to obtain a medicinal residue 1 and volatile oil;

[0076] (2) Mix the formulated amount of peach kernel, angelica and chuanxiong, add 6 times the amount of 90% ethanol and extract for 3 times, each time for 0.5 h, combine the filtrates to obtain the alcohol extract and the residue 2;

[0077] (3) Mixing the residue 1 obtained in step (1) and the residue 2 obtained in step (2) with the formulated amount of leech and Panax notoginseng, adding 14 times the amount of water, reflux extraction 3 times, each time for 3 hours, combining the filtrates, and obtaining a water extract;

[0078] (4) The alcohol extract obtained in step (2) and the water extract obtained in step (3) are combined, concentrated under reduced pressure at 60° C. to a relative density of 1.10-1.12 (60° C.), and the volatile oil obtained in step (1) is added to obtain the pharmaceutical composition.

[0079] Example 3 Preparation of pharmaceutical composition

[0080] The prescription of the pharmaceutical composition is: 15g of Astragalus, 12g of Peach Kernel, 12g of Angelica, 12g of Chuanxiong, 12g of Red Peony Root, 6g of Leech, and 9g of Panax Notoginseng.

[0081] The preparation method is:

[0082] (1) Mix the astragalus and red peony root in the formula amount, add 5 times the amount of water and perform steam distillation for 3 hours to obtain a residue 1 and volatile oil;

[0083] (2) Mix the formulated amount of peach kernel, angelica and chuanxiong, add 8 times the amount of 85% ethanol and extract for 3 times, each time for 1 hour, combine the filtrates to obtain the alcohol extract and the residue 2;

[0084] (3) mixing the residue 1 obtained in step (1) and the residue 2 obtained in step (2) with the formulated amount of leech and Panax notoginseng, adding 12 times the amount of water and reflux extracting for 3 times, each time for 1 hour, combining the filtrates to obtain a water extract;

[0085] (4) The alcohol extract obtained in step (2) and the water extract obtained in step (3) are combined, concentrated under reduced pressure at 60° C. to a relative density of 1.10-1.12 (60° C.), and the volatile oil obtained in step (1) is added to obtain the pharmaceutical composition.

[0086] Comparative Example 1 Preparation of Pharmaceutical Composition

[0087] The difference between this comparative example and Example 3 is that the preparation method is water decoction.

[0088] The preparation method is as follows: mix the formula amount of astragalus, peach kernel, angelica, chuanxiong, red peony root, leech and Panax notoginseng, add 12 times the amount of water and boil for 3 times, each time for 1 hour, combine the filtrate, and concentrate under reduced pressure at 60°C to a relative density of 1.10-1.12 (60°C), which is the pharmaceutical composition.

[0089] Comparative Example 2 Preparation of Pharmaceutical Composition

[0090] The difference between this comparative example and Example 3 is that the preparation method is alcohol extraction.

[0091] The preparation method is as follows: astragalus, peach kernel, angelica, chuanxiong, red peony root, leech and notoginseng are mixed in the prescribed amount, 85% ethanol is added in 8 times amount for alcohol extraction for 3 times, each time for 1 hour, the filtrate is combined, and the filtrate is concentrated under reduced pressure at 60°C to a relative density of 1.10-1.12 (60°C), which is the pharmaceutical composition.

[0092] Comparative Example 3 Preparation of Pharmaceutical Composition

[0093] The difference between this comparative example and Example 3 is that the medicinal materials in each step of the preparation method are different.

[0094] The preparation method is:

[0095] (1) taking a formula amount of Chuanxiong and mixing it, adding 5 times the amount of water and performing steam distillation for 3 hours to obtain a medicinal residue 1 and volatile oil;

[0096] (2) Mix the formula amount of Astragalus, peach kernel and Angelica sinensis, add 8 times the amount of 85% ethanol and extract for 3 times, each time for 1 hour, combine the filtrate, and obtain the alcohol extract and the residue 2;

[0097] (3) mixing the residue 1 obtained in step (1) and the residue 2 obtained in step (2) with the formulated amount of red peony root, leech and Panax notoginseng, adding 12 times the amount of water and reflux extraction for 3 times, each time for 1 hour, combining the filtrates to obtain a water extract;

[0098] (4) The alcohol extract obtained in step (2) and the water extract obtained in step (3) are combined, concentrated under reduced pressure at 60° C. to a relative density of 1.10-1.12 (60° C.), and the volatile oil obtained in step (1) is added to obtain the pharmaceutical composition.

[0099] Comparative Example 4 Preparation of Pharmaceutical Composition

[0100] The difference between this comparative example and Example 3 is that the medicinal materials in each step of the preparation method are different.

[0101] The preparation method is:

[0102] (1) Mix the formula amount of Chuanxiong and red peony root, add 5 times the amount of water and perform steam distillation for 3 hours to obtain a medicinal residue 1 and volatile oil;

[0103] (2) Mix the formulated amount of peach kernel and Panax notoginseng, add 8 times the amount of 85% ethanol and extract for 3 times, each time for 1 hour, combine the filtrates, and obtain the alcohol extract and the residue 2;

[0104] (3) mixing the residue 1 obtained in step (1) and the residue 2 obtained in step (2) with the formula amount of astragalus, leech and angelica, adding 12 times the amount of water and reflux extraction for 3 times, each time for 1 hour, combining the filtrates to obtain a water extract;

[0105] (4) The alcohol extract obtained in step (2) and the water extract obtained in step (3) are combined, concentrated under reduced pressure at 60° C. to a relative density of 1.10-1.12 (60° C.), and the volatile oil obtained in step (1) is added to obtain the pharmaceutical composition.

[0106] Efficacy evaluation

[0107] The femoral vein thrombosis model of mice was used to study the therapeutic effect of the pharmaceutical composition prepared by the present invention on deep vein thrombosis.

[0108] 1. Experimental Animals

[0109] SPF grade KM mice, weight 18-22g, male.

[0110] 2. Experimental drugs

[0111] Pharmaceutical compositions prepared in Examples 1-3 (labeled as S1-S3) and Comparative Examples 1-4 (labeled as D1-D4).

[0112] 3. Experimental methods

[0113] The mice were randomly divided into control group, model group, administration group S1, administration group S2, administration group S3, administration group D1, administration group D2, administration group D3 and administration group D4 according to body weight. The administration group was intragastrically administered with the pharmaceutical composition of the corresponding embodiment and comparative example, with an intragastrically administered dose of 0.5 g crude drug / kg, and the control group and model group were intragastrically administered with an equal volume of physiological saline, and the intragastrically administered was continued for 14 days, once a day.

[0114] On the 8th day, except for the control group, mice in each group were subjected to incomplete ligation to construct a femoral vein thrombosis model in mice. Specifically, the mice were anesthetized by intraperitoneal injection of 10% chloral hydrate (300 mg / kg). After the anesthesia took effect, the mouse hair in the groin was shaved and the skin was disinfected; a longitudinal incision of about 2 cm was made along the midpoint of the left groin area to separate the left femoral vein, and a silk thread was wrapped around the proximal end of the left femoral vein for incomplete ligation to reduce the vascular cavity by about 1 / 2 to slow down the blood flow; 0.4 mL of 10% hypertonic saline was slowly injected from the distal end of the left femoral vein, at which time the femoral vein could be observed to turn dark red, indicating thrombosis; after checking that there was no bleeding in the surrounding tissues, the incision was sutured and sterilized gauze was applied externally. The control group underwent a sham operation without ligation or injection of hypertonic saline, and the rest of the operations were the same as above.

[0115] After the last administration, the mice were fasted but not watered for 12 h, anesthetized intraperitoneally with 5% chloral hydrate, and blood was collected from the abdominal aorta to measure activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB) level, and D-dimer (DD) level.

[0116] The result is shown below.

[0117] Table 1 Effect of drug combination on blood coagulation in mice

[0118]

[0119]

[0120] Note: Different letters in the same column indicate significant differences among the groups (P < 0.05).

[0121] The results showed that compared with the control group, the APTT and TT of the mice in the model group were significantly shortened (P < 0.05), and the FIB and DD were significantly increased (P < 0.05), indicating that the coagulation time of the mice in the model group was significantly shortened, the blood viscosity was significantly increased, the blood was in a high coagulation state, and thrombosis was prone to occur.

[0122] Compared with the model group, the APTT and TT of mice in the drug-treated groups S1-S3 were significantly increased (P < 0.05), and the FIB and DD were significantly decreased (P < 0.05), indicating that the pharmaceutical composition provided in Examples 1-3 of the present invention can significantly prolong the coagulation time, reduce blood viscosity, improve the body state, and prevent thrombosis.

[0123] Comparison of the administration group D1 and the administration groups S1-S3 showed that the APTT, TT, FIB and DD of the mice in the administration groups S1-S3 had significant changes (P < 0.05), indicating that compared with the prior art, the pharmaceutical composition prepared by the improved preparation method of the present invention has significantly improved anti-thrombotic effect.

[0124] Comparison of the administration groups D1-D4 and the administration group S3 shows that the pharmaceutical compositions prepared in comparative examples 1-4 have substantially the same antithrombotic effects (P>0.05), while the pharmaceutical composition prepared in Example 3 has significantly better antithrombotic effects than comparative examples 1-4. This indicates that in the technical solution claimed in the present invention, the change in the extraction process has a greater impact on the efficacy, resulting in significant differences in the antithrombotic effects of the prepared pharmaceutical compositions.

[0125] 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 pharmaceutical composition for treating thrombosis, wherein the raw materials of the pharmaceutical composition are: astragalus, peach kernel, angelica, chuanxiong, red peony root, leech and Panax notoginseng; characterized in that: The preparation method of the pharmaceutical composition comprises the following steps: (1) extracting Astragalus and Red Peony Root to obtain a residue 1 and volatile oil; (2) extracting peach kernel, angelica sinensis and ligusticum chuanxiong with alcohol to obtain medicinal residue 2 and alcohol extract; (3) extracting the medicinal residue 1, the medicinal residue 2, the leech and the Panax notoginseng with water to obtain a water extract; (4) The alcohol extract and the water extract are combined and concentrated, and volatile oil is added to obtain the pharmaceutical composition.

2. The pharmaceutical composition according to claim 1, characterized in that The extraction in step (1) is steam distillation; The amount of water added is 4-7 times the mass of Astragalus and Red Peony Root.

3. The pharmaceutical composition according to claim 1, characterized in that The alcohol extraction in step (2) is reflux extraction using alcohol as solvent; and / or The alcohol is at least one of ethanol, propanol, butanol and pentanol, and / or The volume fraction of the alcohol is 75-90%, and / or The amount of the alcohol is 6-12 times the total mass of peach kernel, angelica and chuanxiong, and / or The number of reflux extractions is 1-5 times, and the time of each reflux extraction is 0.5-3 hours.

4. The pharmaceutical composition according to claim 1, characterized in that The water extraction in step (3) is reflux extraction using water as solvent, and / or The amount of water used is 8-14 times the total mass of astragalus, peach kernel, angelica, chuanxiong, red peony root, leech and notoginseng, and / or The number of reflux extractions is 1-5 times, and the time of each reflux extraction is 1-3 hours.

5. The pharmaceutical composition according to claim 1, characterized in that The pharmaceutical composition comprises the following raw materials by weight: 5-25g of Astragalus, 6-18g of Peach Kernel, 6-18g of Angelica Sinensis, 6-18g of Chuanxiong, 6-18g of Red Peony Root, 2-10g of Leech, 3-15g of Panax Notoginseng, or Astragalus 10-20g, peach kernel 9-15g, Chinese angelica 9-15g, Chuanxiong 9-15g, red peony root 9-15g, leech 4-8g, Panax notoginseng 6-12g, or Astragalus 15g, peach kernel 12g, Chinese angelica 12g, Chuanxiong 12g, red peony root 12g, leech 6g, Panax notoginseng 9g.

6. A method for preparing a pharmaceutical composition for treating thrombosis, wherein the raw materials of the pharmaceutical composition are: astragalus, peach kernel, angelica, chuanxiong, red peony root, leech and Panax notoginseng; comprising the following steps: (1) extracting Astragalus and Red Peony Root to obtain a medicinal residue 1 and volatile oil; (2) extracting peach kernel, angelica sinensis and ligusticum chuanxiong with alcohol to obtain a residue 2 and an alcohol extract; (3) extracting the medicinal residue 1, the medicinal residue 2, the leech and the Panax notoginseng with water to obtain a water extract; (4) The alcohol extract and the water extract are combined and concentrated, and volatile oil is added to obtain the pharmaceutical composition.

7. The preparation method according to claim 6, characterized in that: The extraction in step (1) is steam distillation, and / or The alcohol extraction in step (2) is reflux extraction using alcohol as solvent, and / or The water extraction in step (3) is reflux extraction using water as solvent.

8. Use of the pharmaceutical composition according to any one of claims 1 to 5 or the preparation method according to any one of claims 6 to 7 in preparing a drug for treating thrombosis.

9. A drug for treating thrombosis, characterized in that: The invention comprises the pharmaceutical composition according to any one of claims 1 to 5 and pharmaceutically acceptable excipients.

10. The drug according to claim 9, characterized in that The dosage form of the medicine is capsule, granule, tablet, mixture or syrup.

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