Traditional Chinese medicine composition for promoting blood circulation to remove meridian obstruction and application of traditional Chinese medicine composition in preparation of medicine for treating cerebral apoplexy

Abstract

The invention discloses a traditional Chinese medicine composition for promoting blood circulation to remove meridian obstruction and application of the traditional Chinese medicine composition in preparation of a medicine for treating cerebral apoplexy. The traditional Chinese medicine composition is prepared from radix astragali, radix angelicae sinensis, lumbricus, caulis spatholobi, radix salviae miltiorrhizae, flos carthami, ramulus mori, ground beeltle, radix polygoni multiflori preparata, fructus corni, radix morindae officinalis and cortex eucommiae. A novel traditional Chinese medicine formula is obtained by optimizing compatibility on the basis of a traditional old formula, has the effects of tonifying qi, activating blood circulation, tonifying liver and kidney, dispersing blood stasis and dredging collaterals, repairs brain injury caused by cerebral apoplexy and relieves neurological function defect and brain tissue inflammation, is safe and free of drug liver injury toxicity, and is matched with precise medical treatment of western medicine, the treatment effect on cerebral apoplexy is remarkably improved, and the clinical application prospect is wide. Clinical symptoms of patients are improved, neurological function recovery is promoted, and a new Chinese and western medicine combined treatment strategy is provided for clinic.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine pharmaceutical preparation, and in particular to a traditional Chinese medicine composition for promoting blood circulation and unblocking collaterals and an application thereof in preparing a medicine for treating cerebral stroke. Background Art

[0002] Stroke is a serious neurological disease, which is mainly divided into two categories: ischemic stroke (caused by cerebral vascular obstruction) and hemorrhagic stroke (caused by cerebral vascular rupture), which usually causes local or widespread damage to the brain, causing symptoms such as limb paralysis, speech disorders, and cognitive decline. Acute cerebral infarction (also known as acute ischemic stroke) is the most common type of ischemic stroke, which belongs to the category of "stroke disease" in traditional Chinese medicine. It is believed that it is caused by liver and kidney deficiency and qi and blood deficiency in old age, and abnormal diet and improper work and rest, which lead to endogenous phlegm and blood stasis, poor circulation of qi and blood, and blockage of meridians. Chinese medicine syndrome differentiation belongs to the syndrome of deficiency of the root and excess of the superficial. The superficial symptoms are wind and fire disease, and the root is liver and kidney deficiency and qi and blood deficiency. According to different syndrome types, different Chinese herbal decoctions can be used for treatment. In clinical practice, acute cerebral infarction is more common in the "qi deficiency and blood stasis type".

[0003] Western medicine treatment of acute cerebral infarction mainly relies on thrombolytic drugs, antiplatelet drugs, anticoagulants and supportive therapy to restore cerebral blood flow as soon as possible and reduce brain damage. It faces problems such as time window limitation, side effects and recurrence risk. In recent years, the comprehensive treatment strategy of combining traditional Chinese and Western medicine to treat stroke has gradually received attention, aiming to utilize the precise diagnosis and acute phase treatment capabilities of Western medicine, combined with the long-term conditioning and rehabilitation promotion of traditional Chinese medicine, to achieve better clinical results. How to combine the concept of traditional Chinese medicine syndrome differentiation and treatment with the precision medicine of Western medicine to form a set of scalable and replicable treatment plans is the focus of current research. Summary of the invention

[0004] In order to solve the above problems existing in the prior art, the present invention provides a Chinese medicine composition for promoting blood circulation and unblocking collaterals and its application in preparing a medicine for treating cerebral stroke.

[0005] The first object of the present invention is to provide a Chinese medicine composition for promoting blood circulation and unblocking meridians.

[0006] The second object of the present invention is to provide the use of the traditional Chinese medicine composition and / or its extract in the preparation of a medicine for treating cerebral stroke.

[0007] The third object of the present invention is to provide the use of the traditional Chinese medicine composition and / or its extract in the preparation of a drug for repairing brain damage caused by stroke.

[0008] The fourth object of the present invention is to provide the use of the Chinese medicine composition and / or its extract in the preparation of a drug for alleviating neurological dysfunction and / or brain tissue inflammation caused by stroke.

[0009] The fifth object of the present invention is to provide the use of the Chinese medicine composition and / or its extract as a synergist of Western medicine treatment in the preparation of a drug for treating cerebral stroke.

[0010] The sixth object of the present invention is to provide an oral medicine for treating cerebral stroke.

[0011] The seventh object of the present invention is to provide a method for preparing an oral medicine for treating cerebral stroke.

[0012] In order to achieve the above object, the present invention is implemented by the following scheme:

[0013] A Chinese medicine composition for promoting blood circulation and unblocking meridians is prepared, by weight, from 35 to 45 parts of astragalus, 15 to 20 parts of angelica root, 15 to 20 parts of earthworm, 30 to 38 parts of millettia reticulata, 30 to 38 parts of salvia miltiorrhiza, 10 to 16 parts of safflower, 30 to 38 parts of mulberry twig, 10 to 16 parts of earthworm, 30 to 38 parts of processed polygonum multiflorum, 15 to 20 parts of cornus officinalis, 15 to 20 parts of morinda officinalis and 15 to 20 parts of eucommia.

[0014] Preferably, the medicine is made from 35 parts of astragalus, 15 parts of angelica root, 15 parts of earthworm, 30 parts of millettia reticulata, 30 parts of salvia miltiorrhiza, 10 parts of safflower, 30 parts of mulberry twig, 10 parts of earthworm, 30 parts of processed Polygonum multiflorum, 15 parts of Cornus officinalis, 15 parts of Morinda officinalis and 15 parts of Eucommia ulmoides.

[0015] Preferably, the medicine is made from 40 parts of astragalus, 18 parts of angelica root, 18 parts of earthworm, 35 parts of millettia reticulata, 35 parts of salvia miltiorrhiza, 14 parts of safflower, 35 parts of mulberry twig, 14 parts of earthworm, 35 parts of processed Polygonum multiflorum, 18 parts of Cornus officinalis, 18 parts of Morinda officinalis and 18 parts of Eucommia ulmoides.

[0016] Preferably, the medicine is made from 45 parts of astragalus, 20 parts of angelica root, 20 parts of earthworm, 38 parts of millettia reticulata, 38 parts of salvia miltiorrhiza, 16 parts of safflower, 38 parts of mulberry twig, 16 parts of earthworm, 38 parts of processed Polygonum multiflorum, 20 parts of Cornus officinalis, 20 parts of Morinda officinalis and 20 parts of Eucommia ulmoides.

[0017] The pharmacological properties, functions and indications of each Chinese medicine component in the Chinese medicine composition for promoting blood circulation and unblocking collaterals are as follows:

[0018] Astragalus: The dried root of Astragalusmembranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao or Astragalusmembranaceus (Fisch.) Bge. of the Leguminosae family; sweet and slightly warm; enters the lung and spleen meridians; tonifies qi and raises yang, consolidates the exterior and stops sweating, promotes diuresis and reduces swelling, promotes fluid and nourishes blood, relieves stagnation and arthritis, removes toxins and discharges pus, and heals sores and promotes tissue regeneration; used for qi deficiency and fatigue, poor appetite and loose stools, sinking of qi in the middle, long-term diarrhea and prolapse of the anus, bloody stool and metrorrhagia, spontaneous sweating due to exterior deficiency, qi deficiency and edema, internal heat and thirst, blood deficiency and sallow complexion, hemiplegia, pain and numbness in the arthralgia, carbuncle that is difficult to heal, and long-term sores that do not heal.

[0019] Pheretima: The dried body of Pheretima aspergillum (E.Perrier), Pheretima vulgaris Chen, Pheretima guillelmi (Michaelsen) or Pheretima pectinifera Michaelsen, all of the family Lumbricidae; salty, cold; enters the liver, spleen and bladder meridians; clears away heat and calms the nerves, dredges the meridians, relieves asthma and is a diuretic; used for high fever and coma, epilepsy and convulsions, joint pain, limb numbness, hemiplegia, lung heat, asthma and cough, edema and oliguria.

[0020] Millettia reticulata: dried vine stem of Spatholobus suberectus Dunn, a plant of the Leguminosae family; bitter, sweet, and warm; enters the liver and kidney meridians; promotes blood circulation and replenishes blood, regulates menstruation and relieves pain, relaxes muscles and activates collaterals; used for irregular menstruation, dysmenorrhea, amenorrhea, rheumatic arthralgia, numbness and paralysis, and anemia and chlorosis.

[0021] Salvia miltiorrhiza: the dried root and rhizome of SalviamiltiorrhizaBge., a plant of the Lamiaceae family; bitter, slightly cold; enters the heart and liver meridians; promotes blood circulation and removes blood stasis, dredges the menstruation and relieves pain, clears the heart and relieves restlessness, cools blood and eliminates carbuncles; used for chest pain, abdominal pain, flank pain, accumulation of masses, pain due to heat, restlessness and insomnia, irregular menstruation, dysmenorrhea, amenorrhea, and sores and swelling.

[0022] Safflower: dried flower of Carthamustinctorius L., a plant of the Asteraceae family; pungent, warm; enters the heart and liver meridians; promotes blood circulation and unblocks menstruation, dissipates blood stasis and relieves pain; used for amenorrhea, dysmenorrhea, retained lochia, lumps and masses in the abdomen, chest pain, abdominal pain due to blood stasis, stabbing pain in the chest and ribs, injuries from falls, and sores and swelling.

[0023] Angelica root: The lateral root (root) of the dried root of Angelica sinensis (Oliv.) Diels of the Umbelliferae family is 0.3 to 1 cm in diameter, thick on the top and thin on the bottom, mostly twisted, with a few traces of fibrous roots; sweet and spicy in taste, warm in nature; enters the liver, heart, and spleen meridians; replenishes blood, promotes blood circulation and removes blood stasis, and moisturizes the intestines and promotes bowel movements.

[0024] Morinda officinalis: The dried root of Morinda officinalis How, a plant of the Rubiaceae family; sweet, pungent, and slightly warm; enters the kidney and liver meridians; tonifies kidney yang, strengthens the tendons and bones, and eliminates rheumatism; used for impotence and spermatorrhea, cold speech and infertility, irregular menstruation, cold pain in the lower abdomen, rheumatic arthralgia, and weakness of the tendons and bones.

[0025] Eucommia ulmoides: dried bark of Eucommia ulmoides Oliv., a plant of the Eucommia family; sweet, warm; enters the liver and kidney meridians; tonifies the liver and kidneys, strengthens the tendons and bones, and stabilizes the fetus; used for liver and kidney deficiency, soreness of the waist and knees, weakness of the tendons and bones, dizziness, bleeding during pregnancy, and restless fetus.

[0026] Processed Polygonum multiflorum: a processed product of Polygonum multiflorum (the dried root tuber of Polygonum multiflorum Thunb. of the Polygonaceae family), which is bitter, sweet, astringent, and slightly warm; it enters the liver, heart, and kidney meridians; it nourishes the liver and kidneys, replenishes the essence and blood, blackens the hair, strengthens the tendons and bones, removes turbidity and reduces fat; it is used for blood deficiency and chlorosis, dizziness and tinnitus, premature graying of hair, soreness of the waist and knees, numbness of limbs, metrorrhagia and leukorrhea, and hyperlipidemia.

[0027] Cornus officinalis: the dried mature pulp of Cornus officinalis Sieb. et Zucc., a plant of the Cornaceae family; sour, astringent, and slightly warm; enters the liver and kidney meridians; tonifies the liver and kidneys, astringes and consolidates the body; used for vertigo and tinnitus, soreness of the waist and knees, impotence and spermatorrhea, enuresis and frequent urination, metrorrhagia and leukorrhea, profuse sweating and collapse, internal heat and thirst.

[0028] Mulberry branch: dried young branch of Morusalba L., a plant of the Moraceae family; slightly bitter, neutral; enters the liver meridian; slightly bitter, neutral; enters the liver meridian.

[0029] Chinese earthworm: the dried body of the female Eupolyphagasinensis Walker or Steleophagaplancyi (Boleny), insects of the family Blattidae; salty, cold; slightly toxic; enters the liver meridian; removes blood stasis, repairs tendons and bones; used for traumatic injuries, tendon injuries and fractures, blood stasis and amenorrhea, postpartum abdominal pain due to blood stasis, and lumps and masses.

[0030] "Yinao Tongmai Tang" is a registered preparation of Maoming Traditional Chinese Medicine Hospital (Yueyaozhizi Z05170190), which can invigorate qi and blood, nourish liver and kidney, and activate blood circulation and dredge collaterals, and is mainly used for qi deficiency and blood stasis type of stroke. The present invention is improved on the basis of the old prescription of "Yinao Tongmai Tang", and the new prescription follows the following compatibility principle: Astragalus is the main medicine, earthworm, Millettia reticulata, Salvia miltiorrhiza, safflower and Angelica sinensis are all ministerial medicines, Morinda officinalis, Eucommia barbata, processed Polygonum multiflorum and Cornus officinalis are all adjuvants, and Morinda officinalis and Eucommia ulmoides are all messengers. Astragalus, Angelica sinensis, earthworm, Millettia reticulata, Salvia miltiorrhiza and safflower take the meaning of Buyang Huanwu Tang to invigorate qi, nourish blood and dredge collaterals, and Morinda officinalis and Eucommia ulmoides are used to activate blood circulation, remove blood stasis and dredge collaterals, and processed Polygonum multiflorum, Cornus officinalis, Morinda officinalis and Eucommia ulmoides are used to invigorate liver and kidneys. The above medicines are used together, which has the effects of invigorating qi and activating blood circulation, invigorating liver and kidneys, and removing blood stasis and dredge collaterals, and hits the pathogenesis of acute cerebral infarction.

[0031] The use of any of the above-mentioned Chinese medicine compositions and / or their extracts in the preparation of drugs for treating stroke should also be within the protection scope of the present invention.

[0032] Preferably, the stroke is ischemic stroke.

[0033] More preferably, the ischemic stroke is acute ischemic stroke, i.e., acute cerebral infarction.

[0034] Preferably, the extract is an aqueous extract of the traditional Chinese medicine composition.

[0035] The use of any of the above-mentioned Chinese medicine compositions and / or their extracts in the preparation of drugs for repairing brain damage caused by stroke should also be within the protection scope of the present invention.

[0036] Preferably, the stroke is ischemic stroke.

[0037] More preferably, the ischemic stroke is acute ischemic stroke, i.e., acute cerebral infarction.

[0038] Preferably, the extract is an aqueous extract of the traditional Chinese medicine composition.

[0039] Preferably, the repairing of brain damage caused by stroke includes reducing neurological deficit score, reducing cerebral infarction volume and / or reducing the level of inflammatory cytokines in brain tissue.

[0040] More preferably, the inflammatory cytokines include IL-6 and TNF-α.

[0041] The use of any of the above-mentioned Chinese medicine compositions and / or their extracts in the preparation of drugs for alleviating neurological deficits and / or brain tissue inflammation caused by stroke should also be within the protection scope of the present invention.

[0042] Preferably, the stroke is ischemic stroke.

[0043] More preferably, the ischemic stroke is acute ischemic stroke, i.e., acute cerebral infarction.

[0044] Preferably, the extract is an aqueous extract of the traditional Chinese medicine composition.

[0045] Preferably, the alleviation of neurological deficits caused by stroke includes reducing neurological deficit scores, reducing cerebral infarction volume and / or reducing the levels of inflammatory cytokines in brain tissue.

[0046] More preferably, the neurological impairment score adopts the Longa scoring method.

[0047] More preferably, the inflammatory cytokines include IL-6 and TNF-α.

[0048] The use of any of the above-mentioned Chinese medicine compositions and / or their extracts in the preparation of drugs for improving the efficacy of Western medicine treatment of stroke should also be within the protection scope of the present invention.

[0049] Preferably, the stroke is ischemic stroke.

[0050] More preferably, the ischemic stroke is acute ischemic stroke, i.e., acute cerebral infarction.

[0051] Preferably, the extract is an aqueous extract of the traditional Chinese medicine composition.

[0052] The use of any of the Chinese medicine compositions and / or their extracts as a synergist of Western medicine treatment in the preparation of a medicament for treating stroke should also be within the scope of protection of the present invention. The Western medicine treatment is conventional Western medicine treatment for stroke.

[0053] Preferably, the stroke is ischemic stroke.

[0054] More preferably, the ischemic stroke is acute ischemic stroke, i.e., acute cerebral infarction.

[0055] Further preferably, the Western medicine treatment is carried out with reference to the "Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China 2018".

[0056] Preferably, the extract is an aqueous extract of the traditional Chinese medicine composition.

[0057] An oral medicine for treating cerebral stroke, comprising the Chinese medicine composition and / or its extract.

[0058] Preferably, the oral medication is a liquid preparation, including but not limited to decoctions, wine preparations, lotions, tinctures, syrups and oral solutions.

[0059] Preferably, the liquid preparation is a decoction.

[0060] Preferably, the extract is an aqueous extract of the traditional Chinese medicine composition.

[0061] A method for preparing an oral medicine for treating cerebral stroke comprises the following steps: treating a Chinese medicine composition by a water-adding decoction method, collecting a water extract, and adjusting the amount of the raw medicine to 0.200 g / ml-0.300 g / ml; in parts by weight, the Chinese medicine composition is prepared from 35-45 parts of astragalus, 15-20 parts of angelica root, 15-20 parts of earthworm, 30-38 parts of millettia reticulata, 30-38 parts of salvia miltiorrhiza, 10-16 parts of safflower, 30-38 parts of mulberry twig, 10-16 parts of earthworm, 30-38 parts of processed polygonum multiflorum, 15-20 parts of cornus officinalis, 15-20 parts of morinda officinalis, and 15-20 parts of eucommia.

[0062] Preferably, the medicine is made from 35 parts of astragalus, 15 parts of angelica root, 15 parts of earthworm, 30 parts of millettia reticulata, 30 parts of salvia miltiorrhiza, 10 parts of safflower, 30 parts of mulberry twig, 10 parts of earthworm, 30 parts of processed Polygonum multiflorum, 15 parts of Cornus officinalis, 15 parts of Morinda officinalis and 15 parts of Eucommia ulmoides.

[0063] Preferably, the medicine is made from 40 parts of astragalus, 18 parts of angelica root, 18 parts of earthworm, 35 parts of millettia reticulata, 35 parts of salvia miltiorrhiza, 14 parts of safflower, 35 parts of mulberry twig, 14 parts of earthworm, 35 parts of processed Polygonum multiflorum, 18 parts of Cornus officinalis, 18 parts of Morinda officinalis and 18 parts of Eucommia ulmoides.

[0064] Preferably, the medicine is made from 45 parts of astragalus, 20 parts of angelica root, 20 parts of earthworm, 38 parts of millettia reticulata, 38 parts of salvia miltiorrhiza, 16 parts of safflower, 38 parts of mulberry twig, 16 parts of earthworm, 38 parts of processed Polygonum multiflorum, 20 parts of Cornus officinalis, 20 parts of Morinda officinalis and 20 parts of Eucommia ulmoides.

[0065] Preferably, the crude drug amount is adjusted to 0.250 g / ml.

[0066] Preferably, the preparation method comprises the following steps: fully soaking the Chinese medicine composition in water, then fully decocting, separating the solid and liquid, collecting the liquid, and adjusting the amount of the crude drug to 0.200 g / ml to 0.300 g / ml.

[0067] More preferably, the preparation method comprises the following steps: soaking for 1 to 2 hours with water equivalent to 4 to 8 times the total mass of the traditional Chinese medicine composition, then decocting for 2 to 4 hours, filtering, and collecting medicine soup 1; adding water equivalent to 2 to 6 times the total mass of the traditional Chinese medicine composition to the remaining residue in the previous step, decocting for 1 to 2 hours, filtering, and collecting medicine soup 2; combining medicine soup 1 and medicine soup 2, and concentrating to a raw drug amount of 0.200 g / ml to 0.300 g / ml.

[0068] Further preferably, the preparation method comprises the following steps: soaking for 1 hour with water equivalent to 6 times the total mass of the traditional Chinese medicine composition, then decocting for 2 hours, filtering, and collecting medicine soup 1; adding water equivalent to 4 times the total mass of the traditional Chinese medicine composition to the remaining residue in the previous step, decocting for 1 hour, filtering, and collecting medicine soup 2; combining medicine soup 1 and medicine soup 2, and concentrating to a raw drug amount of 0.200g / ml to 0.300g / ml.

[0069] Further preferably, the preparation method comprises the following steps: soaking in water equivalent to 6 times the total mass of the traditional Chinese medicine composition for 1 hour, then decocting for 2 hours, filtering, and collecting medicine soup 1; adding water equivalent to 4 times the total mass of the traditional Chinese medicine composition to the remaining residue in the previous step, decocting for 1 hour, filtering, and collecting medicine soup 2; combining medicine soup 1 and medicine soup 2, and concentrating to a raw drug amount of 0.250 g / ml.

[0070] Compared with the prior art, the present invention has the following beneficial effects:

[0071] The present invention optimizes the compatibility on the basis of the traditional old prescription to obtain a new Chinese medicine prescription, which has the effects of invigorating qi and activating blood circulation, nourishing the liver and kidney, and removing blood stasis and dredging collaterals, repairing brain damage caused by stroke, and alleviating neurological deficits and brain tissue inflammation. It is safe, has no drug-induced liver damage toxicity, and is coordinated with the precision medicine of Western medicine to significantly improve the therapeutic effect of stroke, improve the patient's clinical symptoms, and promote the recovery of neurological function, providing a new combination of Chinese and Western medicine treatment strategy for clinical practice. DETAILED DESCRIPTION

[0072] The present invention is further described in detail below in conjunction with specific examples, which are only used to explain the present invention and are not used to limit the scope of the present invention. The test methods used in the following examples are conventional methods unless otherwise specified; the materials, reagents, etc. used are reagents and materials that can be obtained from commercial channels unless otherwise specified.

[0073] Embodiment 1 A Chinese medicine composition for promoting blood circulation and unblocking collaterals

[0074] Prescription: 35g Astragalus, 15g Angelica root, 15g Pheretima, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Safflower, 30g Mori branch, 10g Earthworm, 30g Processed Polygonum multiflorum, 15g Cornus officinalis, 15g Morinda officinalis and 15g Eucommia ulmoides.

[0075] Among them, the main medicine is Astragalus, the ministerial medicine is earthworm, Millettia reticulata, Salvia miltiorrhiza, safflower and Angelica sinensis, the adjuvant medicine is Morinda officinalis, Eucommia ulmoides, processed Polygonum multiflorum and Cornus officinalis, and the guiding medicine is Mori twig and Eupolyphaga sinensis.

[0076] Embodiment 2 A Chinese medicine composition for promoting blood circulation and unblocking collaterals

[0077] Prescription: 40g Astragalus, 18g Angelica root, 18g Pheretima, 35g Millettia reticulata, 35g Salvia miltiorrhiza, 14g Carthamus tinctorius, 35g Mori branch, 14g Eucommia ulmoides, 35g processed Polygonum multiflorum, 18g Cornus officinalis, 18g Morinda officinalis and 18g Eucommia ulmoides.

[0078] Among them, the main medicine is Astragalus, the ministerial medicine is earthworm, Millettia reticulata, Salvia miltiorrhiza, safflower and Angelica sinensis, the adjuvant medicine is Morinda officinalis, Eucommia ulmoides, processed Polygonum multiflorum and Cornus officinalis, and the guiding medicine is Mori twig and Eupolyphaga sinensis.

[0079] Embodiment 3 A Chinese medicine composition for promoting blood circulation and unblocking collaterals

[0080] Prescription: 45g Astragalus, 20g Angelica root, 20g Pheretima, 38g Millettia reticulata, 38g Salvia miltiorrhiza, 16g Carthamus tinctorius, 38g Mori branch, 16g Eucommia ulmoides, 38g processed Polygonum multiflorum, 20g Cornus officinalis, 20g Morinda officinalis and 20g Eucommia ulmoides.

[0081] Among them, the main medicine is Astragalus, the ministerial medicine is earthworm, Millettia reticulata, Salvia miltiorrhiza, safflower and Angelica sinensis, the adjuvant medicine is Morinda officinalis, Eucommia ulmoides, processed Polygonum multiflorum and Cornus officinalis, and the guiding medicine is Mori twig and Eupolyphaga sinensis.

[0082] Comparative Example 1 A Chinese medicine composition

[0083] Prescription: 35g Astragalus, 15g Earthworm, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Carthamus tinctorius, 30g Morinda officinalis, 15g Eucommia ulmoides and 15g Eucommia ulmoides.

[0084] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza and Safflower, the adjuvant medicines are Morinda officinalis and Eucommia ulmoides, and the guiding medicine is Morus alba.

[0085] Comparative Example 2 A Chinese medicine composition

[0086] Prescription: 35g Astragalus, 15g Earthworm, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Angelica sinensis root, 30g Mori branch, 15g Morinda officinalis and 15g Eucommia ulmoides.

[0087] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza and Angelica sinensis root, the adjuvant medicines are Morinda officinalis and Eucommia ulmoides, and the guiding medicine is mulberry branch.

[0088] Comparative Example 3: A Chinese medicine composition

[0089] Prescription: 35g Astragalus, 15g Angelica root, 15g Pheretima, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Safflower, 30g Morinda officinalis, 15g Eucommia ulmoides and 15g Eucommia ulmoides.

[0090] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza, safflower and Angelica sinensis, the adjuvant medicines are Morinda officinalis and Eucommia ulmoides, and the guiding medicine is mulberry branch.

[0091] Comparative Example 4: A Chinese medicine composition

[0092] Prescription: 35g Astragalus, 15g Earthworm, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Carthamus tinctorius, 30g Morus alba, 30g Processed Polygonum multiflorum, 15g Morinda officinalis and 15g Eucommia ulmoides.

[0093] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza and safflower, the adjuvant medicines are Morinda officinalis, Eucommia ulmoides and processed Polygonum multiflorum, and the guiding medicine is mulberry branch.

[0094] Comparative Example 5: A Chinese medicine composition

[0095] Prescription: 35g Astragalus, 15g Earthworm, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Carthamus tinctorius, 30g Mori branch, 15g Cornus officinalis, 15g Morinda officinalis and 15g Eucommia ulmoides.

[0096] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza and Safflower, the adjuvant medicines are Morinda officinalis, Eucommia ulmoides and Cornus officinalis, and the guiding medicine is mulberry branch.

[0097] Comparative Example 6 A Chinese medicine composition

[0098] Prescription: 35g Astragalus, 15g Earthworm, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Carthamus tinctorius, 30g Mori branch, 30g Processed Polygonum multiflorum, 15g Cornus officinalis, 15g Morinda officinalis and 15g Eucommia ulmoides.

[0099] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza and safflower, the adjuvant medicines are Morinda officinalis, Eucommia ulmoides, processed Polygonum multiflorum and Cornus officinalis, and the guiding medicine is mulberry branch.

[0100] Comparative Example 7 A Chinese medicine composition

[0101] Prescription: 35g Astragalus, 15g Earthworm, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Carthamus tinctorius, 30g Morus alba, 30g Processed Polygonum multiflorum and 15g Cornus officinalis.

[0102] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza and safflower, the adjuvant medicines are processed Polygonum multiflorum and Cornus officinalis, and the guiding medicine is mulberry branch.

[0103] Comparative Example 8: A Chinese medicine composition

[0104] Prescription: 35g Astragalus, 15g Angelica root, 15g Pheretima, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Safflower, 30g Mori branch, 30g processed Polygonum multiflorum, 15g Cornus officinalis, 15g Morinda officinalis and 15g Eucommia ulmoides.

[0105] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza, safflower and Angelica sinensis root, the adjuvant medicines are processed Polygonum multiflorum and Cornus officinalis, and the guiding medicine is mulberry branch.

[0106] Comparative Example 9: A Chinese medicine composition

[0107] Prescription: 35g Astragalus, 15g Angelica root, 15g Pheretima, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Safflower, 30g Mori branch, 30g processed Polygonum multiflorum, 15g Cornus officinalis, 15g Morinda officinalis and 15g Eucommia ulmoides.

[0108] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza, safflower and Angelica sinensis, the adjuvant medicines are Morinda officinalis, Eucommia ulmoides, processed Polygonum multiflorum and Cornus officinalis, and the guiding medicine is mulberry branch.

[0109] Comparative Example 10 A Chinese medicine composition

[0110] Prescription: 35g Astragalus, 15g Earthworm, 30g Millettia reticulata, 30g Salvia miltiorrhiza, 10g Carthamus tinctorius, 30g Morus alba, 10g Eucommia barbata, 15g Morinda officinalis and 15g Eucommia ulmoides.

[0111] Among them, the main medicine is Astragalus, the ministerial medicines are earthworm, Millettia reticulata, Salvia miltiorrhiza and Safflower, the adjuvant medicines are Morinda officinalis and Eucommia ulmoides, and the guiding medicines are Mori twig and Scolopendra subspinipes.

[0112] Embodiment 4 A method for preparing a Chinese medicine decoction

[0113] According to the Chinese medicine formula, weigh the pieces of each medicinal material, mix them, add water equivalent to 6 times the total weight of the medicinal materials, soak them for 1 hour, then boil them for 2 hours, filter them, and collect the medicine soup; then add water equivalent to 4 times the total weight of the medicinal materials to the residue, boil them for 1 hour, filter them, and collect the medicine soup; combine the two medicine soups and concentrate them to a raw drug amount of 0.250g / ml.

[0114] Application Example 1 Evaluation of therapeutic efficacy in ischemic stroke animal model

[0115] 1. Construction of ischemic stroke rat model

[0116] 1. Experimental Animals

[0117] Specific pathogen-free (SPF) grade SD male rats, 6 weeks old, weighing 180-210 g.

[0118] 2. Model construction

[0119] Referring to the "thread embolization method" in the prior art "Ping Xingfeng, Lv Junying, Li Kai, et al. Establishment and evaluation of a rat model of ischemic stroke with phlegm-heat and visceral excess syndrome [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(11): 2301-2309.", the construction of an ischemic stroke rat model mainly includes the following steps:

[0120] Rats were anesthetized by inducing isoflurane at a concentration of 3% and a flow rate of 0.6 L / min. They were fixed in a supine position on a sterile operating table. The neck was prepared, disinfected, and covered with a towel. A longitudinal incision of about 1.5 cm was made along the middle of the neck, and the tissue was separated layer by layer to fully expose the right carotid triangle. The common carotid artery, external carotid artery, and internal carotid artery were then separated and exposed in sequence. The proximal ends of the common carotid artery and the proximal ends of the external carotid artery were ligated with sterile sutures. Another suture was taken to pull and block the blood flow at the distal end of the internal carotid artery. A small incision was made transversely in the common carotid artery at a distance of 5 mm from the bifurcation of the common carotid artery with vascular scissors. The nylon suture was slowly inserted from the incision with ophthalmic forceps. At the same time, the suture was gently released and slowly pushed in to a depth of about 18 mm, so that the head of the suture reached the starting point of the middle cerebral artery. The suture was fixed and the surgical incision was sutured layer by layer.

[0121] 2. Treatment of ischemic stroke rat model

[0122] 1. Decoction preparation

[0123] The Chinese medicine compositions of Examples 1 to 3 and Comparative Examples 1 to 10 were processed according to the preparation method of Example 4 to prepare corresponding Chinese medicine decoctions.

[0124] 2. Treatment plan

[0125] The rat model of ischemic stroke was randomly divided into 14 groups, 15 rats in each group, and recorded as groups 1 to 14. Among them, groups 1 to 13 were respectively gavaged with the Chinese medicine decoction prepared from the Chinese medicine composition of Examples 1 to 3 and Comparative Examples 1 to 10, with a gavage dose of 5.0 g of raw medicine per rat; group 14 was gavaged with the same amount of drinking water as a control. The gavage was performed once a day for 10 consecutive days.

[0126] 3. Efficacy evaluation

[0127] (1) Neurological deficit score

[0128] After the treatment, the Longa scoring method was used to score the neurological deficits of the rats. The evaluation criteria were: 0 points, normal; 1 point, the right front paw could not be fully extended; 2 points, the rat turned to the right side when walking; 3 points, the rat body leaned to the right side when walking; 4 points, the rat was unable to walk spontaneously and had consciousness disorder.

[0129] (2) Measurement of cerebral infarction volume

[0130] After completing the neurological deficit scoring, the rats were killed, the brain tissue was isolated, and coronal sections were made at 1.5 mm intervals. All brain slices were incubated with TTC stain at 37°C in the dark for 10 min, then photographed, and the cerebral infarction volume was measured using ImageJ software.

[0131] (3) Enzyme-linked immunosorbent assay (ELISA)

[0132] The levels of proinflammatory cytokines IL-6 and TNF-α in the supernatant of brain tissue homogenate were detected according to the ELISA kit instructions.

[0133] (4) Statistical processing

[0134] SPSS 26.0 statistical analysis software was used; all measured data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among multiple groups, and t-test was used for pairwise comparison. P < 0.05 was considered statistically significant.

[0135] 4. Evaluation results

[0136] Table 1 Treatment results of ischemic stroke rat model

[0137]

[0138] (1) Impact on neurological deficits

[0139] The statistical results of neurological deficit scores as shown in Table 1 indicated that compared with group 14, the neurological deficit scores of ischemic stroke rats in groups 1 to 13 were significantly decreased (P<0.05), and the neurological deficit scores of ischemic stroke rats in groups 1 to 3 were further significantly decreased compared with those in groups 4 to 13 (P<0.05).

[0140] (2) Effect on cerebral infarction volume

[0141] The results of TTC staining and the statistical results of cerebral infarction volume as shown in Table 1 showed that compared with group 14, the cerebral infarction volume of ischemic stroke rats in groups 1 to 13 was significantly reduced (P<0.05), and the cerebral infarction volume of ischemic stroke rats in groups 1 to 3 was further significantly reduced compared with groups 4 to 13 (P<0.05).

[0142] (3) Effects on inflammatory cytokine levels in brain tissue

[0143] The statistical results of IL-6 and TNF-α levels as shown in Table 1 indicated that compared with group 14, the levels of IL-6 and TNF-α in the brain tissues of ischemic stroke rats in groups 1 to 13 were significantly decreased (P<0.05), and the levels of IL-6 and TNF-α in the brain tissues of ischemic stroke rats in groups 1 to 3 were further significantly decreased compared with groups 4 to 13.

[0144] The above results indicate that the Chinese medicine composition for promoting blood circulation and unblocking collaterals (Examples 1 to 3) provided by the present invention can repair brain damage caused by ischemic stroke, reduce neurological deficit scores, reduce cerebral infarction volume, and reduce the level of inflammatory cytokines in brain tissue, and has the effect of protecting neurons and reducing neuroinflammation after ischemic stroke.

[0145] Application Example 2 Evaluation of clinical efficacy in ischemic stroke

[0146] 1. Diagnosis of ischemic stroke

[0147] 1. Western medicine diagnosis

[0148] According to the diagnostic criteria for acute ischemic stroke in the "Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China 2018", the main criteria are as follows:

[0149] (1) Acute onset; (2) Focal neurological deficits (weakness or numbness of one side of the face or limbs, language disorders, etc.), and in a few cases, global neurological deficits; (3) The responsible lesion appears on imaging or the symptoms / signs persist for more than 24 hours; (4) Non-vascular causes are excluded; (5) Brain CT / MRI excludes cerebral hemorrhage.

[0150] 2. TCM diagnosis

[0151] Referring to the stroke diagnosis criteria in the "Stroke Diagnosis and Therapeutic Effect Evaluation Criteria" formulated by the National Traditional Chinese Medicine Encephalopathy Emergency Research Collaboration Group of the State Administration of Traditional Chinese Medicine, the main criteria are as follows:

[0152] Main symptoms: hemiplegia, confusion, slurred speech or aphasia, paresthesia on one side of the body, crooked mouth and tongue.

[0153] Secondary symptoms: headache, dizziness, pupil changes, choking when drinking water, unable to blink, and ataxia.

[0154] Acute onset, often with triggers and precursor symptoms. Most cases occur in people over 40 years old.

[0155] If the disease has two or more main symptoms, or one main symptom and two secondary symptoms, the diagnosis can be confirmed by combining the onset, predisposing factors, precursor symptoms, and age. If the above conditions are not met, the diagnosis can also be confirmed by combining the results of imaging examinations.

[0156] Acute phase criteria: within 2 weeks of onset, and up to 1 month for internal organs.

[0157] Standards for Qi deficiency and blood stasis syndrome: hemiplegia, crooked mouth and tongue, slurred speech or silence, decreased or absent sensation, pale complexion, shortness of breath and fatigue, spontaneous sweating, dull tongue, white and greasy tongue coating or with teeth marks, and deep and thready pulse.

[0158] 3. Case exclusion

[0159] The exclusion criteria (including inappropriate conditions or exclusion criteria) were as follows: (1) silent cerebral infarction without symptoms and focal signs; (2) Kubota water test ≥ grade 4; (3) mRS grade 5; (4) ischemic stroke due to causes other than atherosclerosis, such as cardiogenic cerebral embolism, arteritis, polycythemia vera, thrombocythemia, sickle cell anemia, thromboembolic thrombocytopenic purpura, disseminated intravascular coagulation, cerebral amyloid angiopathy, Moyamoya disease, intracranial vascular malformation, etc.; (5) patients with severe heart disease, heart failure, liver dysfunction, renal failure, respiratory failure, malignant tumors, gastrointestinal bleeding, etc. at the time of onset who were not expected to complete the 1-year follow-up; (6) patients with mental illness; (7) patients who could not take medication on time for other reasons; and (8) pregnant and lactating women.

[0160] 2. Clinical Cases

[0161] From January to December 2023, according to the above-mentioned diagnostic method of ischemic stroke, a total of 100 patients with acute cerebral infarction hospitalized in the Department of Encephalopathy of Maoming City Hospital of Traditional Chinese Medicine were included as clinical cases.

[0162] The 100 patients were randomly divided into two groups, 50 in the combined treatment group and 50 in the control group, with an age range of 16 to 80 years old. There was no significant difference in gender, age, onset time and other general data between the two groups (P>0.05), which was comparable.

[0163] 3. Treatment Methods

[0164] Both groups of patients were given conventional Western medicine treatment for acute cerebral infarction, referring to the "Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China 2018" for standardized treatment, including symptomatic supportive treatment such as antiplatelet aggregation, anticoagulation, lipid regulation and plaque stabilization, circulation improvement, and control of underlying diseases.

[0165] The Chinese medicine composition of Example 1 was processed according to the preparation method of Example 4 to prepare a Chinese medicine decoction. For the patients in the combined treatment group, in addition to conventional western medicine treatment, they also took the Chinese medicine decoction of Example 1, 100 ml at a time, once a day, and 14 days as a course of treatment.

[0166] IV. Efficacy evaluation

[0167] The efficacy of Western medicine is assessed based on the National Institutes of Health Neurological Disability Scale (NIHSS).

[0168] The criteria for judging the efficacy of traditional Chinese medicine are evaluated according to the "Stroke Symptom Grading Quantitative Scale" in the "Guidelines for Clinical Research of New Chinese Medicines for the Treatment of Stroke (Trial)" published by China Medical Science and Technology Press in 2001.

[0169] 1. Criteria for determining the efficacy of Western medicine

[0170] (1) Cured: functional impairment score decreased by 90% to 100%, and disability level was 0;

[0171] (2) Significantly effective: functional impairment score decreased by 46% to 89%, and the degree of disability was 1 to 3 grades;

[0172] (3) Effective: functional impairment score decreased by 18% to 45%;

[0173] (4) Ineffective: The functional impairment score decreased or increased within 18%.

[0174] 2. Criteria for determining the efficacy of TCM syndromes

[0175] (1) Cured: TCM clinical symptoms and signs disappeared or almost disappeared, and the syndrome score decreased by ≥95%;

[0176] (2) Significantly effective: clinical symptoms and signs of TCM were significantly improved, and the syndrome score was reduced by ≥70%;

[0177] (3) Effective: clinical symptoms and signs of TCM have improved, and the syndrome score has decreased by ≥30%;

[0178] (4) Ineffective: There was no significant improvement in TCM clinical symptoms and signs, or they even got worse, and the symptom score decreased by less than 30%.

[0179] 3. Adverse reaction monitoring

[0180] To observe the drug-induced liver injury (DILI) in patients in the combined treatment group after taking Chinese herbal decoction.

[0181] The severity of drug-induced liver injury is graded as follows:

[0182] Grade 0 (no liver damage): The patient can tolerate the drug exposure without hepatotoxic reaction.

[0183] Grade 1 (mild liver damage): serum ALT and / or ALP are reversibly elevated, TBil<2.5*ULN (2.5mg / dl or 42.75μmol / L), and INR<1.5. Most patients can adapt. Symptoms may or may not include fatigue, weakness, nausea, anorexia, right upper abdominal pain, jaundice, itching, rash, or weight loss.

[0184] Grade 2 (moderate liver damage): Serum ALT and / or ALP show recoverable elevation, TBil ≥ 2.5*ULN, or INR ≥ 1.5 even though TBil is not elevated. The above symptoms may worsen.

[0185] Grade 3 (severe liver injury): Elevated serum ALT and / or ALP, TBil ≥ 5*ULN (5 mg / dl or 85.5 μmol / L), with or without INR ≥ 1.5. The patient's symptoms worsen further, requiring hospitalization or prolonged hospitalization.

[0186] Grade 4 (ALF): Elevated serum ALT and / or ALP, TBil ≥ 10*ULN (10 mg / dl or 171 μmol / L), or a daily increase of ≥ 1.0 mg / dl (17.1 μmol / L), INR ≥ 2.0 or PTA < 40%, and concurrent presence of (1) ascites or hepatic encephalopathy; or (2) other organ failure related to DILI.

[0187] Grade 5 (fatal): Death due to DILI, or liver transplantation is required for survival.

[0188] 4. Statistical analysis

[0189] SPSS 16.0 statistical software was used to analyze the data. t test was used for the data; chi-square test was used for the data. 2 Test; rank-sum test was used for rank data; P < 0.05 indicated that the difference was statistically significant.

[0190] 5. Evaluation results

[0191] Table 2 Western medicine efficacy evaluation results

[0192]

[0193] Note: The total effective rate of the combined treatment group and the control group was analyzed by rank sum test, P < 0.05, and the difference between the two groups was statistically significant (Z value = -1.976, P = 0.048).

[0194] Table 3 Results of TCM efficacy evaluation

[0195]

[0196]

[0197] Note: The total effective rate of the combined treatment group and the control group was analyzed by rank sum test, P < 0.05, and the difference between the two groups was statistically significant (Z value = -2.059, P = 0.040).

[0198] As shown in Table 2 and Table 3, whether according to the evaluation standards of Western medicine or traditional Chinese medicine, compared with the control group, the therapeutic effect of the patients in the combined treatment group after taking the Chinese medicine decoction of Example 1 was significantly improved.

[0199] Table 4 Drug-induced liver injury

[0200]

[0201] As shown in Table 4, during the treatment, only 2 patients in the combined treatment group experienced mild nausea and gastrointestinal reactions. After timely adjustment of the dosage and medication time, the patients were able to tolerate it without obvious adverse reactions. There were no abnormalities in routine blood and urine tests and liver and kidney functions before and after treatment.

[0202] The Chinese medicine compositions of Examples 2 and 3 were also used to treat the above clinical cases of combined Chinese and Western medicine treatment, and achieved similar treatment results as the Chinese medicine composition of Example 1.

[0203] The above results show that the Chinese medicine composition for promoting blood circulation and unblocking collaterals provided by the present invention can be used in combination with Western medicine treatment to assist Western medicine in treating acute cerebral infarction, effectively improve the patient's clinical symptoms, repair brain damage, promote the recovery of neurological function, and significantly improve the efficacy of clinical conventional Western medicine treatment. It has no drug-induced liver injury toxicity, is safe, effective, and feasible, and is worthy of clinical promotion and application.

[0204] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the protection scope of the present invention. For ordinary technicians in this field, other different forms of changes or modifications can be made based on the above descriptions and ideas. It is not necessary and impossible to list all the implementation methods here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for promoting blood circulation and unblocking meridians, characterized in that: The invention is made from 35 to 45 parts of astragalus, 15 to 20 parts of angelica root, 15 to 20 parts of earthworm, 30 to 38 parts of millettia reticulata, 30 to 38 parts of salvia miltiorrhiza, 10 to 16 parts of safflower, 30 to 38 parts of mulberry twig, 10 to 16 parts of earthworm, 30 to 38 parts of processed polygonum multiflorum, 15 to 20 parts of cornus officinalis, 15 to 20 parts of morinda officinalis and 15 to 20 parts of eucommia bark.

2. Use of the Chinese medicine composition and / or its extract according to claim 1 in the preparation of a medicament for treating cerebral stroke.

3. Use of the Chinese medicine composition and / or its extract according to claim 1 in the preparation of a medicament for repairing brain damage caused by stroke.

4. Use of the Chinese medicine composition and / or its extract according to claim 1 in the preparation of a medicament for alleviating neurological dysfunction and / or brain tissue inflammation caused by stroke.

5. Use of the Chinese medicine composition and / or its extract according to claim 1 as a synergist of Western medicine treatment in the preparation of a medicament for treating cerebral stroke.

6. The use according to any one of claims 2 to 5, characterized in that: The extract is a water extract of the traditional Chinese medicine composition.

7. The use according to any one of claims 2 to 5, characterized in that: The stroke is ischemic stroke.

8. An oral medicine for treating stroke, characterized in that: Contains the Chinese medicine composition and / or its extract according to claim 1.

9. The oral medicine according to claim 8, characterized in that: It is a liquid preparation.

10. A method for preparing an oral medicine for treating stroke, characterized in that: The Chinese medicine composition according to claim 1 is processed by decoction, the water extract is collected, and the amount of the crude drug is adjusted to 0.200 g / ml to 0.300 g / ml.

Images