Traditional Chinese medicine composition and application thereof in treating pulmonary thromboembolism

Abstract

The invention discloses a traditional Chinese medicine composition and application thereof in treating pulmonary thromboembolism. The traditional Chinese medicine composition is prepared from the following raw material medicines: raw astragalus membranaceus, whole angelica sinensis, hairyvein agrimony, pseudo-ginseng powder, madder, radix paeoniae rubra and pericarpium citri reticulatae. According to the traditional Chinese medicine composition disclosed by the invention, the characteristics of the raw material medicines are utilized, the composition is reasonable, the proportioning is scientific, and the optimal medicine effect synergy is achieved; the traditional Chinese medicine composition is exact in curative effect, has a good effect of reducing the bleeding occurrence rate of a patient suffering from the pulmonary thromboembolism in the anticoagulation process, is low in toxicity and high in safety, and can improve the curative effect of anticoagulation treatment of the pulmonary thromboembolism; the invention makes up the current situation of insufficiency of traditional Chinese medicine prescriptions for treating pulmonary thromboembolism, and has the characteristics of wide raw material sources, high safety coefficient, small dosage, and the dosage form meeting clinical requirements.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and relates to a traditional Chinese medicine composition, and specifically relates to a traditional Chinese medicine composition and an application thereof in treating pulmonary thromboembolism.

[0002] Background technology

[0003] Pulmonary thromboembolism (PTE) is a clinical emergency caused by thrombus blocking the pulmonary artery or its branches. It is one of the important manifestations of venous thromboembolism (VTE). Most thrombi originate from the deep veins of the lower extremities (such as the femoral vein and popliteal vein). After falling off, they flow into the pulmonary artery with the blood, causing pulmonary circulation disorders. The clinical manifestations of PTE are diverse. Mild cases may be asymptomatic, while severe cases may cause shock or even sudden death. Typical symptoms include dyspnea, chest pain, and hemoptysis. Its onset is closely related to hereditary thrombophilia (such as antiphospholipid antibody syndrome) and acquired risk factors (such as surgery, long-term immobilization, malignant tumors, etc.). Therefore, early diagnosis and treatment of patients with pulmonary thromboembolism are crucial to improving prognosis.

[0004] Currently, the treatment of pulmonary thromboembolism is mainly divided into anticoagulant therapy, thrombolytic therapy, or interventional / surgical treatment. Anticoagulant therapy is the cornerstone of pulmonary thromboembolism treatment and can prevent the expansion and recurrence of blood clots, but it may increase the risk of bleeding, which can be life-threatening in severe cases. Therefore, it is of great significance to find a drug that can both treat pulmonary thromboembolism and reduce the risk of bleeding in patients. Summary of the invention

[0005] In order to make up for the deficiencies of the prior art, the purpose of the present invention is to provide a Chinese medicine composition and its application in treating pulmonary thromboembolism.

[0006] In order to achieve the above object, the present invention adopts the following technical solution:

[0007] A first aspect of the present invention provides a Chinese medicine composition for treating pulmonary thromboembolism.

[0008] Furthermore, the raw materials of the traditional Chinese medicine composition are: raw astragalus, whole angelica, herb agrimony, notoginseng powder, madder, red peony root and tangerine peel.

[0009] Further, in terms of weight percentage, the ratio of raw astragalus: whole angelica: herbaceous agrimony: notoginseng powder: madder: red peony root: tangerine peel is 10:3:4:1:3:3:2.

[0010] Furthermore, the Chinese medicine composition is prepared from the following raw materials by weight: 30g raw astragalus, 9g whole angelica, 12g herb agrimony, 3g notoginseng powder, 9g madder, 9g red peony root, and 6g tangerine peel.

[0011] In the above composition, the weight of the medicine is calculated based on the raw medicine, and the weight percentage is used as the ratio. It can be increased or decreased in proportion during production. For example, large-scale production can be in kilograms or tons, and small-scale production can also be in grams or milligrams. The weight can be increased or decreased, but the weight ratio of the raw medicines between the components remains unchanged. The above weight ratio is obtained through scientific screening. For special patients, such as severe or mild diseases, obese or thin patients, the ratio of the amount of the components can be adjusted accordingly, and the increase or decrease does not exceed 100%, and the efficacy remains unchanged.

[0012] Furthermore, the Chinese medicine composition also includes active ingredients or pharmaceutically acceptable salts of active ingredients in raw astragalus, whole angelica, herb agrimony, notoginseng powder, madder, red peony root and tangerine peel.

[0013] Furthermore, the pharmaceutically acceptable salts include acid addition salts and base addition salts.

[0014] The term "pharmaceutically acceptable salt" as used herein includes ammonium phosphates, metal salts, salts formed with amino acids, salts formed with amines, and salts formed with other bases such as piperidine or morpholine. The term "pharmaceutically acceptable salt" includes monosalts or disalts. Specific embodiments include ammonium, sodium, calcium, magnesium, cesium, lithium, potassium, barium, zinc, aluminum, lysine, arginine, histidine, methylamine, ethylamine, tert-butylamine, cyclohexylamine, N-methylglucamine, ethylenediamine, glycine, procaine, benzathene, diethanolamine, triethanolamine, piperidine, and morpholine.

[0015] In some embodiments, the term "pharmaceutically acceptable salt" may also include hydrates of pharmaceutically acceptable salts of the active ingredients of the present invention. Examples of salts include, but are not limited to, sulfates, citrates, acetates, oxalates, chlorides, hydrochlorides, bromides, hydrobromides, iodides, nitrates, bisulfates, phosphates, acid phosphates, isonicotinates, lactates, salicylates, acid citrates, tartrates, oleates, tannates, pantothenates, bitartrates, ascorbates, gentisinates, gluconates, glucuronates, saccharates, formates, benzoates, glutamates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, camphorsulfonates, naphthysulfonates, propionates, succinates, fumarates, maleates, malonates, mandelates, malates, palmitates, aspartates, phthalates, and pamoates.

[0016] As used herein, the term "pharmaceutically acceptable salt" also refers to a salt formed by an effective component of the Chinese medicinal material of the present invention having an acidic functional group such as a carboxylic acid functional group and a base. Exemplary bases include, but are not limited to, alkali metals including hydroxides of sodium, potassium and lithium; alkaline earth metals such as hydroxides of calcium and magnesium; other metals such as hydroxides of aluminum and zinc; ammonia, organic amines such as unsubstituted or hydroxy-substituted mono-, di- or trialkylamines, dicyclohexylamine; tributylamine; pyridine; N-methyl, N-ethylamine; diethylamine; triethylamine; mono-, di- or tri-(2-OH-(C1-C6)-alkylamine), such as N, N-dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine; N-methyl-D-glucamine; morpholine; thiomorpholine; piperidine; pyrrolidine; and amino acids such as arginine, lysine, etc.

[0017] In some embodiments, when the Chinese medicine composition of the present invention is administered to a specific individual subject for treatment, the therapeutically effective amount and specific treatment plan for the individual subject may be affected by many factors, including the pharmacodynamic activity of the drug used, the age, weight, general condition, gender, diet, administration time, disease susceptibility, disease progression, and the judgment of the treating physician of the subject. In addition, those skilled in the art are aware that the administration method, dosage form, and dosage of the drug are affected by many factors such as the patient's age, weight, gender, morbidity, diet, administration time, excretion rate, and reaction sensitivity. Therefore, the dosage of the Chinese medicine composition described in the present invention is not limited to the dosage in the embodiments of the present invention, and the same applies to the administration method and dosage form.

[0018] Any Chinese medicine composition encompassed in the present invention can be delivered orally, for example, via any acceptable and suitable oral formulation. Exemplary oral formulations include, but are not limited to, for example, tablets, lozenges, pastilles, aqueous and oily suspensions, dispersible powders or granules, emulsions, hard and soft capsules, liquid capsules, syrups, and elixirs. Pharmaceutical compositions intended for oral administration can be prepared according to any method known in the art for making pharmaceutical compositions intended for oral administration.

[0019] In some embodiments, the prescription used in the present invention uses Astragalus membranaceus as the main ingredient for replenishing the Qi of the lungs and spleen, and Angelica sinensis as the auxiliary ingredient for nourishing blood and activating blood circulation, Herba Agrimoniae Invigorating Qi, tonifying the middle, activating blood circulation and stopping bleeding, Panax notoginseng as the main ingredient for replenishing deficiency, activating blood circulation and stopping bleeding, Rubia cordifolia as the auxiliary ingredient for clearing heat, cooling blood, dispersing blood stasis and relieving pain, and Tangerine peel as the auxiliary ingredient for regulating Qi, strengthening the spleen, drying dampness and resolving phlegm.

[0020] The Chinese medicine composition provided by the present invention is named as the Yifei Tiaoxue Recipe. In the embodiments of the present invention, the terms "Chinese medicine composition", "Chinese medicine" and "Yifei Tiaoxue Recipe" have the same meaning and can be used interchangeably.

[0021] The term "API" used in the present invention refers to the API used to produce pharmaceutical preparations (drugs), which is the source of the active ingredients in the pharmaceutical preparations (drugs). In some embodiments, the term "API" refers to the API used to produce various preparations, which is the active ingredient in the preparations, and is a variety of powders, crystals, extracts, etc. prepared by chemical synthesis, plant extraction or biotechnology for medicinal use, but which cannot be taken directly by patients.

[0022] A second aspect of the present invention provides a pharmaceutical preparation.

[0023] Furthermore, the pharmaceutical preparation includes the traditional Chinese medicine composition described in the first aspect of the present invention.

[0024] Furthermore, the pharmaceutical preparation also includes a pharmaceutically acceptable buffer, carrier and / or excipient.

[0025] Furthermore, the buffer comprises phosphate, carbonate, acetate, citrate, glycolate, lactate, borate, tartrate, and cacodylate.

[0026] Furthermore, the buffer also includes Trizma, Bicine, Tricine, MOPS, MOPSO, MOBS, Tris, Hepes, HEPBS, MES, ACES, ADA, AMP, AMPD, AMPSO, BES, CABS, CHES, DIPSO, EPPS, ethanolamine, glycine, HEPPSO, imidazole, imidazole lactate, PIPES, SSC, SSPE, POPSO, TAPS, TABS, TAPSO, and TES.

[0027] Furthermore, the carrier includes an isotonic agent, an antioxidant, a suspending agent, a dispersing agent, an emulsifier, a chelating agent, a thickener, and a solubilizing agent.

[0028] Furthermore, the excipients include carbohydrates, polymers, lipids, and minerals.

[0029] Furthermore, the dosage forms of the Chinese medicine preparation include granules, tablets, pills, capsules, injections, oral liquids, tinctures, suppositories, mixtures, powders, lotions, films, and pills.

[0030] Furthermore, the pharmaceutically acceptable buffer, carrier and / or excipient are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995). These substances are used to help the stability of the drug or to help improve the activity of the effective active ingredients in the drug as needed. The effective ingredients that can be used in such pharmaceutical compositions can be in the form of their original compounds themselves, or optionally in other pharmaceutically acceptable forms. The pharmaceutical compositions thus formulated can be administered in any appropriate manner known to those skilled in the art as needed.

[0031] Further, pharmaceutically acceptable buffer, carrier and / or excipient may additionally contain liquid, such as water, physiological saline, glycerol and ethanol. In addition, auxiliary substances such as wetting agents or emulsifiers or pH buffer substances may be present in the pharmaceutical composition. These carriers enable the pharmaceutical composition to be formulated into dosage forms such as granules, tablets, pills, capsules, injections, oral liquids, tinctures, mixtures, powders, lotions, films, dripping pills, etc., so that patients can take them.

[0032] The third aspect of the present invention provides a method for preparing a Chinese medicine composition for treating pulmonary thromboembolism.

[0033] Furthermore, the preparation method comprises the following steps: extracting or processing the raw materials of the Chinese medicine composition described in the first aspect of the present invention to obtain its effective ingredients, and then, using the effective ingredients as raw materials, adding pharmaceutically acceptable buffers, carriers and / or excipients when necessary, and preparing the desired dosage form according to conventional pharmaceutical techniques.

[0034] The fourth aspect of the present invention provides use of the Chinese medicine composition described in the first aspect of the present invention in the preparation of a medicament for treating and / or preventing pulmonary thromboembolism.

[0035] The fifth aspect of the present invention provides use of the pharmaceutical preparation described in the second aspect of the present invention in the preparation of a drug for treating and / or preventing pulmonary thromboembolism.

[0036] Advantages and beneficial effects of the present invention:

[0037] The Chinese medicine composition described in the present invention utilizes the inherent characteristics of each component raw material medicine, and is rationally formulated and scientifically proportioned to achieve optimal synergistic efficacy; the Chinese medicine composition has a definite therapeutic effect, has a good effect of reducing the incidence of bleeding during the anticoagulation process of patients with pulmonary thromboembolism, and has low toxicity and high safety, and can also improve the efficacy of anticoagulation treatment of pulmonary thromboembolism; the present invention makes up for the current situation of insufficient traditional Chinese medicine prescriptions for pulmonary thromboembolism, and has the characteristics of a wide source of raw materials, a large safety factor, a small dosage, and a dosage form that meets clinical needs. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 It is a comparison chart of TCM syndrome scores before and after treatment with the Chinese medicine composition of the present invention. DETAILED DESCRIPTION

[0039] In order to make the purpose, technical scheme and beneficial effect of the embodiment of the present invention clearer, the technical scheme in the embodiment of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiment, they are carried out according to the conventional conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified in the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0040] Example 1 Preparation of Chinese medicine composition

[0041] Drug name: Yifei Tiaoxue Fang

[0042] Ingredients: Raw Astragalus 30g, Whole Angelica 9g, Herba Agrimoniae 12g, Notoginseng Powder 3g, Rubia cordifolia 9g, Red Peony Root 9g, Tangerine Peel 6g

[0043] Compatibility: Astragalus is the main ingredient for replenishing the Qi of the lungs and spleen, while Angelica sinensis is the auxiliary ingredient for nourishing blood and activating blood circulation, Herba Agrimoniae replenishes Qi, tonifies the middle, activates blood circulation and stops bleeding, while Panax notoginseng replenishes deficiency, activates blood circulation and stops bleeding, Rubia cordifolia cools blood and removes blood stasis, activates blood circulation and stops bleeding, while Paeonia lactiflora clears heat, cools blood, disperses blood stasis and relieves pain, while Tangerine peel regulates Qi, strengthens the spleen, dries dampness and resolves phlegm are the auxiliary ingredients.

[0044] Effect: Invigorate Qi, warm and promote blood circulation

[0045] Drug decoction method: concentrated decoction, 2 bags per set, 100ml per bag. Specific decoction method: prepare 40 sets, use a 30L decoction pot, add 14.5L of water, soak for 30 minutes, decoct for 70 minutes, packing volume 100ml / bag, a total of 80 bags of finished products, and the remaining liquid medicine is about 200ml.

[0046] Example 2 Clinical efficacy observation test of the Chinese medicine composition of the present invention in treating patients with pulmonary thromboembolism

[0047] The therapeutic effect of the Chinese medicine composition of the present invention on pulmonary thromboembolism is evaluated from the perspective of clinical efficacy. The specific composition ratio selected should not be understood as limiting the weight composition ratio of the drug of the present invention. In combination with the claims, the specification and the general knowledge in the art, without departing from the spirit and scope of the present invention, those skilled in the art may also make any modifications or changes based on the following examples, and such changes are also included in the scope of the present invention.

[0048] 1. Experimental Methods

[0049] (1) Research subjects: Patients with acute pulmonary thromboembolism who visited the outpatient clinic of the Department of Traditional Chinese Medicine Pulmonary Diseases of the China-Japan Friendship Hospital from October 2024 to January 2025.

[0050] 1) Inclusion criteria: ① Age ≥ 18 years old; ② Diagnosis of acute pulmonary thromboembolism; ③ Risk stratification of pulmonary thromboembolism is non-high risk; ④ According to the "Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism", at least one of the following high-risk factors for bleeding: age > 75 years old; history of stroke within 3 months; history of surgery within 3 months; malignant tumor; thrombocytopenia; diabetes; anemia; antiplatelet drug treatment. ⑤ Qi deficiency and blood stasis syndrome (main symptoms: ① shortness of breath, ② chest tightness, ③ fatigue; secondary symptoms: ① chest pain, ② dull complexion, ③ fatigue and laziness, ④ dark purple lips and nails; tongue and pulse: pale or purple tongue with petechiae and ecchymoses on the edges, deep and thin pulse or astringent pulse. At least one of the main symptoms and at least two of the secondary symptoms can be diagnosed by combining the tongue and pulse.).

[0051] 2) Exclusion criteria: ① Patients who need to use warfarin for anticoagulation; ② Patients with significant liver and kidney function abnormalities (any one of ALT, AST, Cr, BUN exceeds the upper limit of the normal reference value by more than 3 times); ③ Patients with severe digestive system, nervous system, blood system, cardiovascular and cerebrovascular diseases or severe mental illness; ④ Patients who have received thrombolytic, interventional or surgical treatment.

[0052] (2) Experimental plan: On the basis of anticoagulation with low molecular weight heparin or rivaroxaban, patients were treated with Yifei Tiaoxue prescription. Yifei Tiaoxue prescription consists of 30g raw astragalus, 9g whole angelica, 12g herba agrimonii, 3g notoginseng powder, 9g madder, 9g red peony root, 6g tangerine peel, decocted, 1 dose per day, 2 times a day, 100ml each time. The course of treatment is 12 weeks.

[0053] Outcome indicators: ①Main outcome indicators: bleeding events (including major bleeding and clinically relevant non-major bleeding); ②Secondary outcome indicators: all-cause mortality, venous thromboembolism-related mortality; ③Exploratory outcome indicators: TCM syndrome score (main symptoms: 0 points, 2 points, 4 points, and 6 points for none, mild, moderate, and severe, respectively; secondary symptoms: 0 points, 1 point, 2 points, and 3 points for none, mild, moderate, and severe, respectively), TCM syndrome efficacy (efficacy index (n) = (pre-test score-post-test score) / pre-test score × 100%. Clinical cure: clinical symptoms and signs disappeared or basically disappeared, and the syndrome score decreased by ≥95%; marked effect: clinical symptoms and signs were significantly improved, and the syndrome score decreased by ≥70%, <95%; effective: clinical symptoms and signs were improved, and the syndrome score decreased by ≥30%, <70%; ineffective: clinical symptoms and signs were not significantly improved, or even aggravated, and the syndrome score decreased by less than 30%.)

[0054] 2. Experimental Results

[0055] A total of 33 patients with acute pulmonary thromboembolism with high risk factors for bleeding were included in this study, and no deaths were observed during the treatment. During the treatment, a total of 4 cases had clinically relevant non-major bleeding events, and no patients had major bleeding events during medication, with a total bleeding rate of 12.12%. Among the 4 bleeding cases, 3 were skin and mucosal bleeding (2 cases showed bruising around the eyes, and 1 case showed gingival bleeding), and 1 was gastrointestinal bleeding (manifested as blood in the stool, a small amount of fresh blood). Based on domestic prospective real-world research data, the incidence of major bleeding within 3 months of anticoagulant treatment for pulmonary thromboembolism is 3.0%, and the incidence of clinically relevant non-major bleeding is 16.5%. In this study, the incidence of bleeding events in the combination of Yifei Tiaoxue Fang and conventional Western medicine anticoagulation was lower than that in previous studies using conventional Western medicine anticoagulation alone.

[0056] In terms of the efficacy of TCM syndrome, 12 cases were clinically cured, 16 cases were significantly effective, 3 cases were effective, and 2 cases were ineffective, with a total effective rate of 93.94%. The TCM syndrome score of the patient was 12.24±5.53 points before treatment, 4.85±4.09 points after 4 weeks of treatment, and 2.61±3.65 points after 12 weeks of treatment. The TCM syndrome scores after 4 weeks of treatment and 12 weeks of treatment were statistically different from those before treatment (P<0.05), and the TCM syndrome scores after 4 weeks of treatment were statistically different from those after 12 weeks of treatment (P<0.05). The TCM syndrome scores of each main symptom and secondary symptom after 4 weeks of treatment and 12 weeks of treatment were statistically different from those before treatment (P<0.05). The TCM syndrome scores of other main symptoms and secondary symptoms except chest pain were statistically different after 4 weeks of treatment and 12 weeks of treatment (P<0.05) (see Figure 1 ).

[0057] The description of the above embodiments is only used to understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several modifications and changes can be made to the present invention without departing from the principles of the present invention, and these modifications and changes will also fall within the scope of protection of the claims of the present invention.

Claims

1. A Chinese medicine composition for treating pulmonary thromboembolism, characterized in that: The raw materials of the traditional Chinese medicine composition are as follows: raw astragalus, whole angelica, herba agrimonii, notoginseng powder, madder, red peony root and tangerine peel.

2. The Chinese medicine composition according to claim 1, characterized in that: By weight percentage, the ratio of raw astragalus: whole angelica: herbaceous agrimony: notoginseng powder: madder cordifolia: red peony root: tangerine peel is 10:3:4:1:3:3:

2.

3. The Chinese medicine composition according to claim 1 or 2, characterized in that: The Chinese medicine composition is prepared from the following raw materials by weight: 30g of raw astragalus, 9g of whole angelica, 12g of herbaceous agrimony, 3g of notoginseng powder, 9g of madder, 9g of red peony root, and 6g of tangerine peel.

4. A pharmaceutical preparation, characterized in that The pharmaceutical preparation comprises the Chinese medicine composition according to any one of claims 1 to 3.

5. The pharmaceutical preparation according to claim 4, characterized in that The pharmaceutical preparation also includes a pharmaceutically acceptable buffer, carrier and / or excipient.

6. The pharmaceutical preparation according to claim 5, characterized in that The buffer includes phosphate, carbonate, acetate, citrate, glycolate, lactate, borate, tartrate, cacodylate; Preferably, the carrier includes an isotonic agent, an antioxidant, a suspending agent, a dispersing agent, an emulsifier, a chelating agent, a thickener, and a solubilizing agent; Preferably, the excipients include carbohydrates, polymers, lipids, minerals.

7. The pharmaceutical preparation according to any one of claims 4 to 6, characterized in that The dosage forms of the traditional Chinese medicine preparation include granules, tablets, pills, capsules, injections, oral liquids, tinctures, suppositories, mixtures, powders, lotions, films, and pills.

8. A method for preparing a Chinese medicine composition for treating pulmonary thromboembolism, characterized in that: The preparation method comprises the following steps: extracting or processing the raw materials of the Chinese medicine composition according to any one of claims 1 to 3 to obtain its effective ingredients, and then, using the effective ingredients as raw materials, adding pharmaceutically acceptable buffers, carriers and / or excipients when necessary, and preparing the desired dosage form according to conventional pharmaceutical techniques.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating and / or preventing pulmonary thromboembolism.

10. Use of the pharmaceutical preparation according to any one of claims 4 to 7 in the preparation of a drug for treating and / or preventing pulmonary thromboembolism.

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