WO2022021636A1 - 一种健脾活络中药组合物及其应用 - Google Patents

一种健脾活络中药组合物及其应用 Download PDF

Info

Publication number
WO2022021636A1
WO2022021636A1 PCT/CN2020/124302 CN2020124302W WO2022021636A1 WO 2022021636 A1 WO2022021636 A1 WO 2022021636A1 CN 2020124302 W CN2020124302 W CN 2020124302W WO 2022021636 A1 WO2022021636 A1 WO 2022021636A1
Authority
WO
WIPO (PCT)
Prior art keywords
parts
diabetes
treatment
spleen
diabetic
Prior art date
Application number
PCT/CN2020/124302
Other languages
English (en)
French (fr)
Inventor
陈超
吴邦泰
许旭昀
陈秋铭
王叙煌
陈子睿
吴典伟
谢希
林玺
林俊和
Original Assignee
汕头市中医医院
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 汕头市中医医院 filed Critical 汕头市中医医院
Publication of WO2022021636A1 publication Critical patent/WO2022021636A1/zh

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/488—Pueraria (kudzu)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/236—Ligusticum (licorice-root)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284—Atractylodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/34—Campanulaceae (Bellflower family)
    • A61K36/344—Codonopsis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/756—Phellodendron, e.g. corktree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Definitions

  • the invention relates to the field of traditional Chinese medicine formulations, in particular to a traditional Chinese medicine composition for strengthening the spleen and activating collaterals.
  • Diabetes is a common and frequently-occurring disease in clinical practice.
  • Prof. Ning Guang's team surveyed the prevalence of diabetes and prediabetes among people over 18 years old in China, reaching 11.6% and 50.1%, respectively.
  • the prevalence of diabetes in my country is increasing year by year, especially in recent years, the prevalence rate has risen sharply, the development trend is not optimistic, and the incidence has changed.
  • Epidemiological data show that more than 80% of diabetics are obese in my country.
  • Diabetes modern Chinese medicine mostly belongs to the category of "diabetes” in Chinese medicine.
  • “Thirsty and desire” means “dry mouth and desire to drink”.
  • this disease name is a generalization of patients with similar symptoms.
  • Ancient physicians formed various theories when discussing the pathogenesis of diabetes mellitus.
  • Physicians of past dynasties have enriched and developed the pathogenesis of the disease, including the theory of yin deficiency and dryness, the theory of three eliminations, the theory of liver stagnation and qi stagnation, and the theory of blood stasis. Dispelling and other pathogenesis understanding.
  • Diabetic peripheral neuropathy is the most common chronic complication of diabetes and the main cause of disability. Modern medicine believes that it is mainly due to the disturbance of nerve microvascular energy supply, resulting in insufficient supply of neurotrophic nutrients, resulting in the death of neuronal cells Ken Schwann cells, resulting in neuronal death. damaged.
  • Diabetic retinopathy (DR) is a common fundus complication caused by diabetes. It is the most serious microvascular disease of diabetes, which can seriously affect the optic nerve function of patients and cause peripheral nerve dysfunction.
  • Strict control of blood sugar is the basis for preventing and delaying nerve and vascular disease, but ideal blood sugar control cannot completely prevent the occurrence of nerve and vascular disease. Therefore, controlling blood sugar alone cannot completely achieve the purpose of preventing nerve and vascular disease.
  • Traditional Chinese medicine has unique advantages in preventing and improving diabetes and its complications. However, there are few proprietary Chinese medicines for the treatment of middle and late stage diabetes, especially those complicated with peripheral neuropathy and peripheral vascular disease.
  • the purpose of the present invention is to provide a traditional Chinese medicine composition for strengthening the spleen and activating collaterals, which harmonizes the spleen and stomach, strengthens the spleen and replenishes qi, promotes blood circulation and clears the collaterals, attacks and supplements simultaneously, is compatible, and has obvious characteristics in the treatment of diabetes. It is safe and effective in patients with diabetes and its complications caused by spleen deficiency and collateral stasis in the middle and late stages.
  • Another object of the present invention is to apply the above-mentioned Chinese medicinal composition for strengthening the spleen and activating collaterals in the preparation of medicines for the treatment of diabetes and its complications.
  • a kind of traditional Chinese medicine composition for strengthening the spleen and activating collaterals is characterized in that: by weight, the formula is made up of the following components: 15-25 parts of Pueraria lobata, 12-18 parts of Salvia miltiorrhiza, 25-35 parts of Atractylodes Rhizoma Codonopsis, 25-35 copies of Codonopsis, 8-12 copies of Treats, 8-12 copies of Shichangpu, 12-18 copies of Dilong, 8-12 copies of Chuanxiong, 25-35 copies of Astragalus, and 8-12 copies of Tianqi.
  • the formula is composed of the following components: 18-22 parts of Pueraria Root, 14-16 parts of Salvia miltiorrhiza, 28-32 parts of Atractylodes Rhizoma, 28-32 parts of Codonopsis Radix, 9-11 parts of Treats, 9-11 parts of Shichangpu 11 parts, Dilong 14-16 parts, Chuanxiong 9-11 parts, Astragalus 28-32 parts, Tian Qi 9-11 parts.
  • the formula is made up of the following components: 20 parts of Pueraria lobata, 15 parts of Salvia miltiorrhiza, 30 parts of Atractylodes Rhizoma, 30 parts of Codonopsis Radix, 10 parts of Treats, 10 parts of Shichangpu, 15 parts of Dilong, 10 parts of Chuanxiong , 30 parts of Astragalus, 10 parts of Tian Qi.
  • the medicine is decoction, granule, tablet, capsule, oral liquid or pill.
  • the medicine is a preparation prepared by using the extracts of the components in the formula of the Chinese medicine composition for strengthening the spleen and activating collaterals as active ingredients and adding medicinal excipients.
  • the extract is a water extract.
  • diabetes diabetic peripheral neuropathy, diabetic peripheral vascular disease, diabetic retinopathy, diabetes combined with coronary heart disease or diabetes combined with cerebral infarction are the late stage of diabetes mellitus, diabetic peripheral neuropathy, diabetic peripheral vascular disease, diabetic retinopathy of spleen deficiency and collateral stasis type. , Diabetes complicated with coronary heart disease or diabetes complicated with cerebral infarction.
  • the present invention is a formula for "treatment of diabetes from the spleen and stomach", which has the functions of strengthening the spleen and replenishing qi, promoting blood circulation and dredging collaterals, and is used for quenching thirst caused by spleen deficiency and collateral stasis, symptoms such as dry mouth and polydipsia, polyphagia and polyuria, Shenpi fatigue, pale or dark complexion, fullness in the abdomen and abdomen, poor appetite, wrong skin and nails, numbness and pain in limbs, mainly tingling, aggravated at night, intermittent limping, hemiplegia, crooked corners of the mouth, dull tongue with petechiae , white coating, deep and fine pulse, etc.; diabetes and diabetic peripheral neuropathy, diabetic vascular disease, diabetic ocular fundus disease, diabetes combined with coronary heart disease, diabetes combined with cerebral infarction and other symptoms have obvious curative effect after taking it.
  • the invention is a traditional Chinese medicine composition for invigorating the spleen and activating collaterals. Calculated in parts by weight, the formula is composed of the following components: 15-25 parts of Pueraria, 12-18 parts of Salvia miltiorrhiza, 25-35 parts of Atractylodes Rhizoma, 25-35 parts of Codonopsis Radix, and 8 parts of Treats -12 copies, 8-12 copies of Shichangpu, 12-18 copies of Dilong, 8-12 copies of Chuanxiong, 25-35 copies of Astragalus, and 8-12 copies of Tianqi.
  • the formula is composed of the following components: 18-22 parts of Pueraria Root, 14-16 parts of Salvia miltiorrhiza, 28-32 parts of Atractylodes Rhizoma, 28-32 parts of Codonopsis Radix, 9-11 parts of Treats, 9-11 parts of Shichangpu 11 parts, Dilong 14-16 parts, Chuanxiong 9-11 parts, Astragalus 28-32 parts, Tian Qi 9-11 parts.
  • the formula is made up of the following components: 20 parts of Pueraria lobata, 15 parts of Salvia miltiorrhiza, 30 parts of Atractylodes Rhizoma, 30 parts of Codonopsis Radix, 10 parts of Treats, 10 parts of Shichangpu, 15 parts of Dilong, 10 parts of Chuanxiong , 30 parts of Astragalus, 10 parts of Tian Qi.
  • diabetes diabetic peripheral neuropathy, diabetic peripheral vascular disease, diabetic ocular fundus disease, diabetes combined with coronary heart disease or diabetes combined with cerebral infarction.
  • diabetes complicated with coronary heart disease diabetes complicated with cerebral infarction
  • diabetic peripheral neuropathy, diabetic peripheral vascular disease or diabetic eye disease Especially in the treatment of late-stage diabetes patients who are manifested by spleen deficiency and collateral stasis, diabetes complicated with coronary heart disease, diabetes complicated with cerebral infarction, diabetic peripheral neuropathy, diabetic peripheral vascular disease or diabetic eye disease.
  • the medicament can be in oral dosage forms such as decoction, granule, tablet, capsule, oral liquid or pill.
  • the medicine is a corresponding preparation prepared by using the extracts of the components in the formula of the Chinese medicine composition for strengthening the spleen and activating the collaterals as active ingredients, and adding pharmaceutical excipients of corresponding dosage forms according to the existing general process.
  • the extract is a water extract.
  • the formula of the present invention comes from the theoretical system of the inventor's "Treatment of Diabetes from the Spleen and Stomach", and it is believed that the pathogenesis of diabetes is: "The spleen and stomach are out of balance, the things are not naturalized, the subtleties are not transported, and the organs are out of nourishment", so the treatment is to reconcile the spleen and stomach, attack and supplement both Shi is the core. Diabetes is mostly manifested as spleen deficiency, stagnation and heat in the early stage, blood stasis in the collaterals, in the middle stage of spleen and lung deficiency, heart and spleen deficiency, and spleen and kidney deficiency.
  • the symptoms of diabetes mellitus are mainly consumption of more food, dry mouth and more drinking.
  • the metabolism, transportation and transformation of diet are most closely related to the spleen and stomach. So, how is water metabolized into the human body?
  • “Plain Questions: The Differentiation of Meridians” says: “Drinking enters the stomach, escaping the essence and qi, and transporting it upward to the spleen, dispersing the spleen, returning to the lungs, regulating the water channels, and transporting the bladder downward.
  • food and water grains enter the human body, decompose through the stomach, metamorphose into the subtle substances, and transport and transform through the spleen to spread the subtle substances throughout the body to support the functional activities of the whole body.
  • Diabetes the thirst for a long time, fat, sweet and thick taste, the change of the cream, the internal injury to the spleen and stomach, the spleen deficiency, the phlegm-dampness is endogenous, and the hair is diabetes.
  • the spleen and stomach are located in the middle coke, which transports and transforms water and valleys. If the spleen fails to function properly, the spleen cannot disperse the essence, the upper essence cannot be transferred to the lungs, and the lower essence cannot be transported to the bladder, and the viscera cannot be nourished. Damage to the spleen and stomach of the middle burner, passive blood biochemistry, deficiency of qi and blood, and lack of righteousness, not only cause diabetes, but also various syndromes.
  • Deficiency syndrome is mainly qi deficiency and yin deficiency.
  • Deficiency syndrome is mostly manifested as spleen deficiency and lung heat, spleen deficiency and stomach deficiency, spleen deficiency and liver stagnation. , and develop into a syndrome of yin and yang deficiency or spleen deficiency and collateral obstruction.
  • Concurrent syndromes are mostly evidence, mainly stagnation, heat, dampness, phlegm, turbidity, and blood stasis, often caused by multiple evil qi intermingled with each other, or appearing in the entire course of diabetes, or more prominent at a certain stage. Therefore, reconciling the spleen and stomach, attacking and nourishing as the core treatment method, and nourishing the spleen and strengthening the core are the core. In the process of strengthening the righteousness, attention must be paid to exorcising evil spirits.
  • Atractylodes atractylodes invigorates the spleen and replenishes qi and dries dampness, while Codonopsis pilosula invigorates the middle and replenishes qi, so that the central axis can be transported. It is a king medicine.
  • Atractylodes macrocephala in this recipe can promote the recovery of damaged autonomic nerve function, adjust the balance of human viscera functions, regulate gastrointestinal motility, lower blood sugar, diuresis, and enhance resistance. Codonopsis polysaccharide can reduce alloxan-induced diabetes.
  • Astragalus has the functions of resisting free radical damage and enhancing immunity
  • Salvia contains a large amount of diterpene quinone pigment, tanshinone, danshensu, two It has the functions of promoting blood circulation and removing blood stasis, reducing blood viscosity, etc., and can well improve the blood viscosity of diabetic patients.
  • Chuanxiong has sedative and analgesic, inhibiting the release of oxygen free radicals, etc., and Tianqi can dilate blood vessels, Improve microcirculation disorders, lower blood lipids, scavenge free radicals, anti-inflammatory, anti-oxidation, etc., improve fundus microcirculation and retinal ischemia and hypoxia;
  • Pueraria lobata has hypoglycemic effects, and the preparations of Pueraria lobata and its extracts have been Widely used in the treatment of diabetes and its complications, calamus can improve immunity, anti-tumor, lipid-lowering, anti-inflammatory, and earthworm can improve microcirculation, regulate blood pressure, improve atherosclerosis and hemangioma, and improve blood flow, etc.
  • Cortex Phellodendri has various pharmacological effects, mainly including hypoglycemic, antibacterial, antifungal, antitussive, antihypertensive, anti-trichomoniasis, anti-hepatitis, anti-ulcer and immunosuppressive effects.
  • the clinical treatment of diabetes in the present invention is generally based on reconciling the spleen and stomach, attacking and supplementing and applying it as the core, and creating a prescription for strengthening the spleen and activating collaterals.
  • this prescription is good for strengthening the spleen and replenishing qi, promoting blood circulation and dredging collaterals, and is especially suitable for
  • the treatment of diabetic peripheral neuropathy and diabetic peripheral vascular disease caused by spleen deficiency and collateral stasis in the late stage of diabetes is effective, safe and reliable.
  • the formula consists of the following components: 20g of Pueraria lobata, 15g of Salvia miltiorrhiza, 30g of Atractylodes Rhizoma, 30g of Codonopsis Radix, 10g of Treats, 10g of Shichangpu, 15g of Dilong, 10g of Chuanxiong, 30g of Astragalus, and 10g of Tianqi. Add water and cook to a bowl.
  • Embodiment 2 (decoction)
  • the formula consists of the following components: 18g of pueraria, 14g of Salvia miltiorrhiza, 28g of Atractylodes, 28g of Codonopsis, 9g of Treats, 9g of Shichangpu, 14g of Dilong, 0g of Chuanxiong, 28g of Astragalus, and 9g of Tianqi. Add water and cook to a bowl.
  • Embodiment 3 (decoction)
  • Each dose of the formula is composed of the following components: 22g of Pueraria lobata, 16g of Salvia miltiorrhiza, 32g of Atractylodes Rhizoma, 32g of Codonopsis Radix, 11g of Treats, 11g of Shichangpu, 16g of Dilong, 10g of Chuanxiong, 32g of Astragalus, and 11g of Tianqi. Add water and cook to a bowl.
  • the formula consists of the following components: 20g of Pueraria lobata, 14g of Salvia miltiorrhiza, 30g of Atractylodes Rhizoma, 32g of Codonopsis Radix, 9g of Treats, 11g of Shichangpu, 16g of Dilong, 11g of Chuanxiong, 28g of Astragalus, and 11g of Tianqi. Add water and cook to a bowl.
  • the formula is composed of the following components: 25 parts of Pueraria lobata, 18 parts of Salvia miltiorrhiza, 35 parts of Atractylodes Rhizoma, 35 parts of Codonopsis Radix, 12 parts of Treats, 12 parts of Shichangpu, 18 parts of Dilong, 12 parts of Chuanxiong, 35 parts of Astragalus, Tianqi 12 copies. Extract with water twice, add 8-10 times of water each time, decoct for 1-1.5 hours, combine the water extracts, concentrate and dry to obtain dry extract.
  • Example 5 Take 20 g of the dry extract obtained in Example 5 and grind it into fine powder, according to the capsule manufacturing process, add medicinal starch and micropowder silica gel, mix, sieve, and put into capsules to make 100 capsules to obtain capsules. The content of each capsule weighs 0.2g.
  • TCM syndrome differentiation criteria dry mouth and excessive drinking, mental fatigue, pale complexion, fullness in the abdomen and abdomen, poor appetite, numbness and pain in limbs, mainly tingling, aggravating at night, intermittent claudication, hemiplegia, dull tongue with petechiae , white fur, pulse is fine and astringent.
  • Both groups were given comprehensive diabetes treatment, including health education, diet management, exercise management, blood glucose monitoring and management, etc., oral hypoglycemic drugs or routine treatment with insulin.
  • the control group was orally administered Micobao tablets, 0.5 mg each time, 3 times/d.
  • the observation group was additionally treated with the Jianpi Huoluo Decoction of Example 1, decocted in water, 1 dose per day, 1 dose per day, decocted into 400 mL, 200 mL each time, warmed twice in the morning and evening, and the treatment results were counted after 4 weeks of treatment.
  • ancient traditional Chinese medicine mostly treats it from “dryness and heat due to yin deficiency”.
  • the current clinical findings have changed in terms of etiology, pathogenesis and pathogenesis, clinical manifestations, and even treatment methods.
  • Diagnostic criteria 1 Referring to the diagnostic criteria of DR in "Modern Diagnosis and Treatment of Diabetes"; 2 the main syndrome of TCM syndrome differentiation belongs to the patients with spleen deficiency and collateral stasis that can be treated with the spleen invigorating and activating collateral formula of the present invention.
  • control group was given calcium dobesilate capsules (Beijing Jingfeng Pharmaceutical Group Co., Ltd., H20010795) 0.5g, orally three times a day.
  • an automatic blood flow analyzer (Tianjin Tangyu Medical Device Technology Development Co., Ltd.) to detect blood rheological indicators: plasma viscosity, whole blood viscosity (high shear), whole blood viscosity (middle shear), whole blood viscosity (low shear) cut), erythrocyte aggregation index, erythrocyte stiffness index and fibrinogen (FIB).
  • VEGF decreased (P ⁇ 0.05), while Ang-1 and SOD increased (P ⁇ 0.05).
  • VEGF in the group was lower than that in the control group during the same period of treatment (P ⁇ 0.05), while Ang-1 and SOD were higher than those in the control group during the same period of treatment (P ⁇ 0.05). See Table 4.
  • DR is mainly developed on the basis of quenching thirst and spleen deficiency. Diabetes the thirst for a long time, the deficiency of both qi and yin, the deficiency of qi and yin, the inability to transport blood, the blood stasis due to qi deficiency, and the stasis of blood in the eyes and collaterals; in addition, most of the patients are old and weak, the kidney essence is deficient, the liver blood is insufficient, and the essence and blood are difficult to flourish.
  • DR is mostly a syndrome of deficiency and deficiency.
  • Microvascular disease is the basic link in the pathogenesis of DR. It is manifested as the expansion of capillary non-perfusion area, the atresia of large retinal vessels, severe ischemia and hypoxia, and finally the formation of new blood vessels. This process involves a variety of cytokines.
  • VEGF is a vascular endothelial growth factor, and its high expression can promote the formation of new blood vessels in DR, enhance vascular permeability, induce endothelial cell growth, and also promote retinal oxidative stress state, induce inflammatory response, and aggravate retinal damage.
  • Ang-1 can regulate angiogenesis, inhibit the expression of VEGF and vascular proliferation, and improve the stability of endothelial cells.
  • SOD can indirectly reflect the antioxidant capacity in the body.
  • the retinal tissue may appear telangiectasia, resulting in traction retinal detachment, resulting in blindness of the patient.
  • Hyperglycemia causes fundus microcirculation disorder, activates protein kinase C, catalyzes the activation of endothelial nitric oxide synthase, and promotes angiogenesis.
  • low blood perfusion produces more free radicals, activates some genes that induce apoptosis, and increases the attention to nerve damage.
  • microvascular emboli Due to the small retinal blood vessels, once the plasma viscosity, whole blood viscosity, erythrocyte aggregation index and FIB increase, it is easy to form microvascular emboli, reduce the oxygen tolerance of the retina, and promote the generation of blood vessels. Compensatory expansion, resulting in the formation of hemangioma, causing or aggravating the patient's condition.
  • DR is mostly caused by deficiency of the spleen spleen and blood stasis, and the formation of eye collaterals. , improve vision level, treat both the symptoms and root causes, high safety, worthy of clinical application.
  • the treatment group there were 26 males and 14 females; the age ranged from 45 to 76 years, with an average of (54.1 ⁇ 2.2) years; the course of disease was 3 to 20 years, with an average of (10.5 ⁇ 3.2) years.
  • In the control group there were 21 males and 19 females; the age ranged from 43 to 77 years, with an average of (53.3 ⁇ 3.1) years; the course of disease was 2 to 19 years, with an average of (10.1 ⁇ 1.3) years.
  • P>0.05 There was no significant difference in gender, age, course of disease and other general data between the two groups (P>0.05), which was comparable.
  • the diagnostic criteria of western medicine refer to the "Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2017 Edition)" to formulate the criteria.
  • Neuropathy caused by other causes such as cervical and lumbar spondylosis (nerve root compression, spinal stenosis, cervical and lumbar degenerative changes), cerebral infarction, Guillain-Barré syndrome; severe arteriovenous vascular disease (venous embolism, Lymphangitis), etc.; neurotoxic effects caused by drugs, especially chemotherapy drugs, and damage to nerves caused by metabolic poisons caused by renal
  • Basic treatment conventional western medicine treatment. Including diabetic diet, moderate exercise, health education, oral appropriate hypoglycemic drugs or insulin injection.
  • the blood glucose control level was 5.0-8.0 mmol/L fasting blood glucose and 5.0-10.0 mmol/L before bedtime.
  • Control group On the basis of basic treatment, each patient was given 500 ⁇ g of mecobalamin tablets orally three times a day.
  • Treatment group On the basis of the treatment of the control group, each patient was added with the prescription of Example 1, decocted into 400 mL, 200 mL each time, and warmed twice in the morning and evening.
  • the TCSS score includes neurological symptoms, reflexes and sensory scores: (1) Symptoms: numbness or no sensation in the lower limbs, pain (burning pain or electric shock-like pain), fatigue, needle-like sensation, unsteady walking, and ask whether there are similarities in the upper limbs symptom. 0 points for no abnormality, 1 point for one symptom, 6 points in total; (2) Reflex: ankle and knee reflex, 8 points in total, 0 points for no abnormality, 1 point for one side weakening, 2 points for disappearance; (3) ) Feeling: Check 5 items of pain, vibration, position, touch and temperature of the right thumb. No abnormality is scored as 0, one symptom is scored as 1, a total of 5 points. The total score of 3 inspections is 19 points.
  • VPT Vibration Perception Threshold
  • the assessment scale refers to the simple scale of quality of life SF-36, which is approved by the World Health Organization (WHO) and has reliable reliability.
  • the scale contains 8 dimensions, covering life functions and functions, physical pain, energy, general health, emotional and mental health, etc. Each dimension is scored separately and then accumulated. This is the original score, which is then converted into a total average score through a standard formula. The score ranges from 0 to 100. The higher the score, the better the quality of life.
  • Table 8 compares the efficacy of the three groups of patients [n (%)]
  • Vibration sensory threshold (VPT) examination-foot sensory nerve is a specific indicator for the diagnosis of diabetic peripheral neuropathy, and it is a commonly used clinical standard for evaluating diabetic peripheral neuropathy and its treatment effect.
  • the results of this study show that after the comparison before and after treatment and the comparison between groups, Jianpi Huoluo Fang can significantly improve the clinical symptoms of patients with diabetic peripheral neuropathy, improve clinical efficacy, improve the quality of life of patients, and enhance patients' confidence in treatment. It has no obvious adverse reactions, is simple and easy to operate, and has strong operability, which is worthy of clinical application.
  • the treatment group there were 31 males and 19 females; the age ranged from 45 to 77 years, with an average of (54.1 ⁇ 2.1) years; the course of disease was 3 to 19 years, with an average of (10.4 ⁇ 3.2) years.
  • the control group there were 26 males and 24 females; the age ranged from 42 to 75 years, with an average of (53.2 ⁇ 3.0) years; the disease duration was 2 to 21 years, with an average of (10.1 ⁇ 1.4) years.
  • P>0.05 There was no significant difference in gender, age, course of disease and other general data between the two groups (P>0.05), which was comparable.
  • Basic treatment conventional western medicine treatment. Including diabetic diet, moderate exercise, health education, oral appropriate hypoglycemic drugs or insulin injection.
  • the blood glucose control level was 5.0-8.0 mmol/L fasting blood glucose and 5.0-10.0 mmol/L before bedtime.
  • Control group On the basis of basic treatment, each patient was given aspirin enteric-coated tablet 100mg qn and atorvastatin calcium 20mg qn orally.
  • Treatment group On the basis of the treatment of the control group, each patient was added with the prescription of Example 1, decocted into 400 mL, 200 mL each time, and warmed twice in the morning and evening.
  • CIMT Carotid intima-media thickness
  • ABI evaluation method Refer to "Guidelines for Diagnosis and Treatment of Arteriosclerosis Obliterans of Lower Limbs” (2015).
  • ABI calculation method the ratio of the systolic blood pressure of the ankle artery (posterior tibial artery or dorsal foot artery) to the systolic blood pressure of the upper arm (take the higher side of the left and right arms).
  • ABI evaluation method normal range: 1.00-1.40; critical range: 0.91-0.99; lower extremity ischemia: ⁇ 0.9.
  • symptom efficacy index (integration before treatment-integration after treatment)/integration before treatment ⁇ 100%. If the efficacy of symptoms is inconsistent with the efficacy of ABI, the one with better efficacy shall prevail.
  • the Jianpi Huoluo prescription of the present invention can significantly improve the clinical symptoms of patients with diabetic peripheral vascular disease, improve clinical efficacy, improve the quality of life of patients, and enhance patients' confidence in treatment , and no obvious adverse reactions, simple and easy to operate, strong operability, worthy of clinical application.
  • Diabetic patients are mainly characterized by abnormally high blood sugar, which leads to blood viscosity and slow blood flow, which can lead to serious complications such as cardiovascular disease.
  • Coronary heart disease (CHD) is a common cardiovascular complication of diabetes, characterized by myocardial ischemia and hypoxia caused by coronary atherosclerosis and lumen stenosis.
  • CHD coronary heart disease
  • my country's aging trend has accelerated, coupled with changes in dietary structure, the incidence of diabetes mellitus with coronary heart disease has increased year by year, and timely treatment is needed to improve the prognosis of patients.
  • Jianpi Huoluo Fang to treat diabetes mellitus with coronary heart disease, and obtained good curative effect, which is summarized as follows:
  • the subjects included in this study were randomly selected from 83 patients with diabetes and coronary heart disease admitted to Shantou Hospital of Traditional Chinese Medicine from December 2018 to December 2019. All patients met the diagnostic criteria for coronary heart disease and diabetes, and informed consent to this study.
  • the above 83 patients with diabetes and coronary heart disease were randomly divided into control group of 41 cases and treatment group of 42 cases. There were 27 males and 15 females in the treatment group; the age ranged from 37 to 80 years old, with an average age of (49.34 ⁇ 11.13) years old.
  • the course of disease ranged from 5 months to 5 years, with an average course of (2.51 ⁇ 0.21) years; the body weight was 42kg to 78kg, with an average body weight of (57.31 ⁇ 8.25)kg.
  • the control group consisted of 27 males and 14 females, aged 37-79 years, with an average age of (49.10 ⁇ 11.53) years.
  • the disease course ranged from 5 months to 5 years, with an average course of (2.56 ⁇ 0.25) years; the body weight was 42kg to 78kg, and the average weight was (57.92 ⁇ 8.45)kg.
  • the general data of the two groups of patients, the difference was statistically significant P>0.05, comparable.
  • TCM syndrome differentiation criteria dry mouth and polydipsia, chest tightness or chest pain, mental fatigue, sallow complexion, fullness of the abdomen and abdomen, poor appetite, paralysis and pain of limbs, mainly tingling, worsening at night, intermittent claudication, hemiplegia, pale tongue Dark with petechiae, white fur, and thin and astringent pulse.
  • the control group was given conventional western medicine treatment, oral hypoglycemic drugs or insulin injection to control the blood sugar level to 3.9-7.8 mmol/L, and given simvastatin to regulate lipids and stabilize plaques, combined with routine dietary guidance and exercise guidance.
  • Example 1 of the present invention Chinese medicine treatment was added to the treatment group, and the decoction of Example 1 of the present invention (hereinafter referred to as the spleen-invigorating and activating-loose formula) was taken orally, one dose per day.
  • the two groups were compared (1) the total effective rate of diabetes complicated with coronary heart disease treatment; (2) the differences of fasting blood glucose, E/A, plasma viscosity and erythrocyte aggregation index between patients before and after intervention.
  • SPSS 21.0 software was used to count the data of patients with diabetes mellitus complicated with coronary heart disease.
  • the enumeration data was tested by ⁇ 2 , and the measurement data was by t test. P ⁇ 0.05 was considered to be statistically significant.
  • the treatment group had a higher total effective rate in the treatment of diabetes complicated with coronary heart disease, and the difference was statistically significant (P ⁇ 0.05), as shown in Table 13.
  • the results show that compared with the control group, the treatment group has a higher total effective rate in the treatment of diabetes combined with coronary heart disease, and the improvement of fasting blood glucose, E/A, plasma viscosity, and red blood cell aggregation index is more significant.
  • Coronary heart disease has an exact curative effect, can effectively improve blood glucose and cardiac function, and improve hemodynamics, which is beneficial to the prognosis of patients, and is worthy of promotion.
  • the disease is mainly characterized by lacunar infarction, small artery infarction, and middle artery infarction, and has a high incidence and recurrence rate.
  • the inventors applied Jianpi Huoluo Fang to treat diabetes mellitus with coronary heart disease, and obtained good curative effect, which is summarized as follows:
  • the patients in the control group received routine treatment, namely, symptomatic treatment such as lowering intracranial pressure, lowering lipids and controlling blood sugar, and closely monitored the blood sugar of the patients.
  • routine treatment namely, symptomatic treatment such as lowering intracranial pressure, lowering lipids and controlling blood sugar, and closely monitored the blood sugar of the patients.
  • the observation group was given the decoction of Example 1 on the basis of the treatment of the control group, decoction in water, 1 dose per day, and twice in the morning and evening. 1 course of treatment is 1 month.
  • NIHSS National Institutes of Health Stroke Scale
  • Basic recovery the clinical symptoms completely disappear, and the neurological deficit score is reduced by 91% to 100% compared with that before treatment.
  • the disability level is grade 0;
  • markedly effective clinical symptoms are significantly improved, the degree of neurological deficit is reduced by 46% to 90% compared with before treatment, and the degree of disability is grade 1 to 3;
  • effective clinical symptoms are alleviated, neurological function Defect score decreased by 18% to 45% compared with before treatment;
  • Ineffective no change in clinical symptoms, neurological deficit score decreased by ⁇ 18% compared with before treatment, and even the disease further developed and deteriorated.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

一种健脾活络中药组合物及其应用，按重量份数计算，由以下组分组成：葛根15-25份、丹参12-18份、白术25-35份、党参25-35份、黄柏8-12份、石菖蒲8-12份、地龙12-18份、川芎8-12份、黄芪25-35份、田七8-12份。该中药组合物具有健脾益气，活血通络的功效，用于治疗脾虚络瘀所致的糖尿病及糖尿病周围神经病、糖尿病血管病变、糖尿病眼底病变，糖尿病合并冠心病、糖尿病合并脑梗塞等，疗效显著。

Description

一种健脾活络中药组合物及其应用 技术领域
本发明涉及中药组方领域，特别是一种健脾活络中药组合物。
背景技术
糖尿病是临床常见病、多发病，2010年宁光教授团队在中国18岁以上的人群中调查的糖尿病和糖尿病前期的患病率分别达到11.6％和50.1％。我国糖尿病患病率逐年增加，尤其是近几年患病率骤升，发展趋势不容乐观，且发病情况有所变化，有流行病学资料显示我国糖尿病肥胖者占80％以上。
糖尿病，现代中医多归属于中医学“消渴”范畴。消渴病相关的论述最早见于《内经》，有“消瘅”，“三消”，“膈消”“消中”等病名。《说文解字》中的解释：“消，尽也”，为“消瘦、消散、消耗”的意思。“渴，欲也”，为“口干欲饮”的意思。从字面上的概念看，此病名是对存在类似症状病人的归纳。古代医家论述消渴病的病机时形成了多种学说，历代医家对该病病机都有丰富和发展，形成了包括阴虚燥热说、三消说、肝郁气滞说、瘀血致消说等病机认识。
目前多认为，病变脏腑多责之肺胃肾，基本病机为“阴虚为本，燥热为标”，治疗则重在“养阴清热”。
然而,现今临床发现不论是病因病机与发病，还是临床表现，乃至治疗方法，都与古代不同。申请人在长期临床实践中发现，现代糖尿病人饮水连连却不解其渴，所饮之水不能化生津液而小便频频；消渴病人多食而易饥，且肌肤不荣，所食水谷不养四肢而形体消瘦；现代之消渴病人肥胖者居多，肥人多痰，痰湿素盛，湿盛伤脾，典型“阴虚燥热型消渴”的病人已经少见，养阴则助湿碍脾，清热则伤脾阳而痰湿更甚。所以，不管“阴虚”还是“燥热”，都只是消渴病的“标”，只看到消渴的症状，而忽视疾病的根本。
现代糖尿病病机已从“阴虚燥热”，演变为“脾胃虚弱、清阳不升、湿浊下注、相火郁闭”，脾胃元气不足,来自下焦之湿浊阴火乘机上乘，消耗人体的气血津液,气血津液施布障碍，不循常道而致“消渴”，应以“补脾胃、升清阳、泻湿浊、降阴火”治之。
现代糖尿病人中后期多出现严重周围血管、周围神经病变、眼底病变，表现为脾虚络瘀。糖尿病周围神经病变作为糖尿病最常见的慢性合并症和主要致残原因，现代医学认为主要是由于神经微血管供能障碍，导致神经营养供应不足，使得神经元细胞肯施旺氏细胞死亡，从而导致神经受损。糖尿病视网膜病变(DR)是由糖尿病引起的常见眼底并发症，是糖尿病最严重的微血管病变，可严重影响患者的视神经功能，引起周围神经功能障碍，是导致患者失明的主要原因，治疗较为棘手。其现代医学 发病机制主要为糖代谢异常，长期的高血糖引起蛋白质糖基化，引起视网膜细微动脉损害，血管通透性增加，血管基底膜增厚而出现DR。视网膜微创手术治疗具有一定疗效，主要采用视网膜激光光凝、止血、扩张血管、改善微循环等，但其为有创性，并发症较多，对视神经功能的改善效果不甚理想，因此药物治疗仍是临床主要治疗手段，尤其是Ⅰ、Ⅱ、Ⅲ期视网膜病变者。严格控制血糖是预防和延缓神经、血管病变的基础，但血糖控制理想并不能完全防止发生神经、血管病变，因此单靠控制血糖并不能完全达到防止神经、血管病变的目的。中医药在预防和改善糖尿病及其并发症上有独特的优势。然而，关于治疗糖尿病中后期，尤其是并发周围神经病变、周围血管病变的中成药较少，有的着重于益气活血，通络止痛，如木丹颗粒；有的着重于养阴益气，清热活血，如养阴降糖片，有的着重于养阴清热，活血化瘀，益气固肾，如糖脉康颗粒，有的着重于益气养阴，活血化瘀，如芪蛭降糖胶囊等等，暂无与本发明健脾益气，活血通络功效相近的相关研究，市场暂无此类品种供应。
发明内容
为解决现有技术的问题，本发明的目的是提供一种健脾活络中药组合物，其调和脾胃，健脾益气，活血通络，攻补兼施，配伍精当，理法特色明显，治疗糖尿病中后期脾虚络瘀所致糖尿病及其并发症患者安全有效。
本发明的另一个目的是将上述健脾活络中药组合物应用于制备治疗糖尿病及其并发症的药物上。
发明的目的是这样实现的：一种健脾活络中药组合物，其特征在于：按重量份数计算，配方由以下组分组成：葛根15-25份、丹参12-18份、白术25-35份、党参25-35份、黄柏8-12份、石菖蒲8-12份、地龙12-18份、川芎8-12份、黄芪25-35份、田七8-12份。
优选的，按重量份数计算，配方由以下组分组成：葛根18-22份、丹参14-16份、白术28-32份、党参28-32份、黄柏9-11份、石菖蒲9-11份、地龙14-16份、川芎9-11份、黄芪28-32份、田七9-11份。
最优选的，按重量份数计算，配方由以下组分组成：葛根20份、丹参15份、白术30份、党参30份、黄柏10份、石菖蒲10份、地龙15份、川芎10份、黄芪30份、田七10份。
所述健脾活络中药组合物在制备治疗糖尿病、糖尿病周围神经病变、糖尿病周围血管病、糖尿病眼底病变、糖尿病合并冠心病或糖尿病合并脑梗塞的药物的应用。
所述的药物为汤剂、颗粒剂、片剂、胶囊剂、口服液或丸剂。
所述的药物为以所述健脾活络中药组合物配方中组分的提取物为有效成分，添加药用辅料制得的制剂。
所述的提取物为水提取物。
所述的糖尿病、糖尿病周围神经病变、糖尿病周围血管病、糖尿病眼底病变、糖尿病合并冠心病 或糖尿病合并脑梗塞是脾虚络瘀型的糖尿病后期、糖尿病周围神经病变、糖尿病周围血管病、糖尿病眼底病变、糖尿病合并冠心病或糖尿病合并脑梗塞。
本发明是“从脾胃论治糖尿病”的组方，具有健脾益气，活血通络之功，用于脾虚络瘀所致的消渴，症见口干多饮、多食、多尿，神疲乏力，面色萎黄或黧黑，脘腹胀满，食纳不香，肌肤甲错，肢体麻痹疼痛，以刺痛为主，夜间加重，间歇性跛行，半身不遂，口角歪斜，舌淡暗有瘀点，苔白，脉沉细涩等；糖尿病及糖尿病周围神经病、糖尿病血管病变、糖尿病眼底病变，糖尿病合并冠心病、糖尿病合并脑梗塞等见上述证候者服用后均有明显疗效。
具体实施方式
发明是一种健脾活络中药组合物，按重量份数计算，配方由以下组分组成：葛根15-25份、丹参12-18份、白术25-35份、党参25-35份、黄柏8-12份、石菖蒲8-12份、地龙12-18份、川芎8-12份、黄芪25-35份、田七8-12份。优选的，按重量份数计算，配方由以下组分组成：葛根18-22份、丹参14-16份、白术28-32份、党参28-32份、黄柏9-11份、石菖蒲9-11份、地龙14-16份、川芎9-11份、黄芪28-32份、田七9-11份。最优选的，按重量份数计算，配方由以下组分组成：葛根20份、丹参15份、白术30份、党参30份、黄柏10份、石菖蒲10份、地龙15份、川芎10份、黄芪30份、田七10份。
所述健脾活络中药组合物在制备治疗糖尿病、糖尿病周围神经病变、糖尿病周围血管病、糖尿病眼底病变、糖尿病合并冠心病或糖尿病合并脑梗塞的药物的应用。尤其是治疗表现为脾虚络瘀所致的糖尿病后期患者，糖尿病合并冠心病、糖尿病合并脑梗塞、糖尿病周围神经病变、糖尿病周围血管病或糖尿病眼底病变患者。
所述的药物可以为汤剂、颗粒剂、片剂、胶囊剂、口服液或丸剂等口服剂型。所述的药物为以所述健脾活络中药组合物配方中组分的提取物为有效成分，添加相应剂型的药用辅料按已有通用工艺制得的相应制剂。优选的，所述的提取物为水提取物。
本发明组方来自发明人“从脾胃论治糖尿病”理论体系，认为糖尿病病机为：“脾胃失调，物不归化，精微不运，脏腑失养”，故治疗以调和脾胃，攻补兼施为核心。糖尿病早期多表现为脾虚郁热，脉络瘀滞，中期脾肺两虚、心脾两虚、脾肾两虚，后期损及阴阳，而发展为阴阳两虚或脾虚络瘀之证。
消渴病症状以消耗多食，口干多饮为主，饮食的代谢与运化，与脾胃关系最为密切。那么，水饮进入人体如何代谢的呢？《素问·经脉别论》云：“饮入于胃，游溢精气，上输于脾，脾气散精，上归于肺，通调水道，下输膀胱。水精四布，五经并行”。正常情况下，饮食水谷进入人体，经胃之腐熟，化生精微物质，经脾之运化，将精微物质散布全身，支持全身功能活动。当饮食失常，脾胃受损时，就要发病。可见，早在《内经》时期就明确提出了消渴发病或因过食肥甘厚味，内伤脾胃，或因 胃中积热，根本在于“脾胃”。
(一)脾胃失调，物不归化，日久则内生热、郁、湿、痰、浊、瘀。
饮食肥甘厚味，损伤脾胃，运化不及，体内的糟粕无法通过脾胃升清降浊作用排出，蕴积肠腑而生内热，煎灼津液，则燥邪、热邪内生，发为消渴病。
消渴日久，肥甘厚味，膏粱之变，内伤脾胃，脾虚则痰湿内生，发为消渴。
情志抑郁、肝气不舒，瘀血郁久化热也会导致消渴的病机。
(二)脾失健运，精微不运，脏腑失养，则气血亏虚，日久阴阳俱虚。
脾胃居中焦，运化水谷，为气机升降之枢纽，气血生化之来源。若脾失健运，则脾不能散精，精微上不能归于肺，下不能输于膀胱，则脏腑失养。中焦脾胃受损，血液生化无源，气血亏虚，正气不足，不只发为消渴，又可出现多种变证。血脉失养，经络不和，可见肢体麻痹之证；肝肾阴亏，不能上养耳目，可见视瞻昏渺、暴盲、耳聋等证；瘀阻络脉，正气亏虚，易感热毒而发疮疖、痈疽。
本发明结合大量临床实际，认为消渴临床常见虚实夹杂之证，且虚实夹杂贯穿消渴病整个病程。虚证以气虚、阴虚为主，一般而言，早期多表现为脾虚肺热、脾虚胃实、脾虚肝郁，中期脾肺两虚、心脾两虚、脾肾两虚，后期损及阴阳，而发展为阴阳两虚或脾虚络阻之证。兼证多为实证，以郁、热、湿、痰、浊、瘀为主，往往由多个邪气互相夹杂为病，或出现于消渴的整个病程，或在某个阶段较为突出。因此，调和脾胃，攻补兼施为核心治疗方法，补脾扶正是核心，在扶正的过程中，必需重视驱邪。
现代糖尿病人中后期多出现严重周围血管、周围神经病变，表现为脾虚络瘀，针对这样的病情特点，以本发明健脾活络方治疗，对糖尿病及并发症疗效肯定、确切。方中白术健脾益气燥湿，党参补中益气，使中轴得运，共为君药；配伍黄芪补一身之气，丹参、川芎、田七以活血化瘀通脾络，益气以助活血，共为臣药；佐以葛根升清阳以通脾络，解热以生津止渴，川菖蒲化湿开胃，理气豁痰辟浊，地龙活血通络，并用黄柏清热燥湿助脾以泻降阴火，引火归元为使药。全方升降和合，共凑健脾益气，活血通络之功。
根据现代研究，此方中白术，具有促进受损植物神经功能的恢复，调整人体脏腑功能平衡和调节胃肠运动、降糖、利尿、增强抵抗力等作用，党参多糖能够降低四氧嘧啶致糖尿病小鼠的血糖,同时能在一定程度上改善胰岛素抵抗,提高机体胰岛素的敏感性；黄芪具有抗自由基损伤、增强免疫力等功能；丹参含有大量的二萜醌色素、丹参酮、丹参素、二基醛等多种物质,具有活血化瘀、降低血液粘度等作用,能很好的改善糖尿病患者的血黏度状况，川芎具有镇静镇痛、抑制氧自由基释放等作用，田七能够扩张血管、改善微循环障碍、降血脂、清除自由基、抗炎、抗氧化等作用，改善眼底微循环及视网膜的缺血缺氧状态；葛根有降血糖作用，以葛根组方及其提取物的制剂已广泛用于糖尿病及其 并发症的治疗，菖蒲可以改善免疫、抗肿瘤、降脂、抗炎，地龙具有改善微循环、调节血压、改善动脉粥样硬化及血管瘤、改善血液流变等作用；黄柏具有多方面药理作用，主要包括降糖、抗菌、抗真菌、镇咳、降压、抗滴虫、抗肝炎、抗溃疡以及免疫抑制作用等。
因此，本发明临床治疗糖尿病总体以调和脾胃，攻补兼施为核心，创立健脾活络方，通过下述临床研究的数据，用数据证明本方功善健脾益气，活血通络，尤其适用于治疗糖尿病后期表现为脾虚络瘀所致的糖尿病周围神经病变及糖尿病周围血管病变患者，疗效确切、安全可靠。
实施例1(汤剂)
配方由以下组分组成：葛根20g、丹参15g、白术30g、党参30g、黄柏10g、石菖蒲10g、地龙15g、川芎10g、黄芪30g、田七10g。加水煎煮至一碗服用。
实施例2(汤剂)
配方由以下组分组成：葛根18g、丹参14g、白术28g、党参28g、黄柏9g、石菖蒲9g、地龙14g、川芎0g、黄芪28g、田七9g。加水煎煮至一碗服用。
实施例3(汤剂)
配方每剂由以下组分组成：葛根22g、丹参16g、白术32g、党参32g、黄柏11g、石菖蒲11g、地龙16g、川芎10g、黄芪32g、田七11g。加水煎煮至一碗服用。
实施例4(汤剂)
配方由以下组分组成：葛根20g、丹参14g、白术30g、党参32g、黄柏9g、石菖蒲11g、地龙16g、川芎11g、黄芪28g、田七11g。加水煎煮至一碗服用。
实施例5(片剂)
按重量份计算，配方由以下组分组成：葛根25份、丹参18份、白术35份、党参35份、黄柏12份、石菖蒲12份、地龙18份、川芎12份、黄芪35份、田七12份。水提两次，每次加8-10倍的水，煎煮1-1.5小时，合并水提液，浓缩干燥，得到干浸膏。
取干浸膏20g研磨成细粉，按片剂制造工艺，加入药用淀粉和微粉硅胶，混合、制粒、干燥、整粒，然后加入硬脂酸镁，混匀，压制成100片，即得片剂。每片重0.3g。
实施例6(胶囊剂)
取实施例5制得的干浸膏20g研磨成细粉，按胶囊剂制造工艺，加入药用淀粉和微粉硅胶，混合、过筛、装入胶囊中，制成100粒，即得胶囊。每粒内容物重重0.2g。
临床对比实验
为了客观评价本发明中药组合物的临床有效性与安全性，按照中药新药临床研究指南的要求，对该药进行临床研究。以下研究均经汕头市中医院伦理委员会批准，患者均对本研究知情同意。
一、治疗糖尿病的临床研究
1资料与方法
1.1一般资料 将2016年1月-2018年1月就诊于汕头市中医院糖尿病科门诊及住院部的64例糖尿病周围神经病变的患者，随机分为两组：健脾活络方治疗组和对照组。观察组32例，男17例，女15例，平均年龄(58.2±6.8)岁，糖尿病病程(10.5±3.1)年，糖尿病周围神经病变病程(6.8±4.6)年，空腹血糖(7.1±2.0)mmol/L；对照组32例，男20例，女12例，年龄(57.9±5.3)岁，糖尿病病程(11.8±4.2)年，糖尿病周围神经病变病程(7.1±2.2)年，空腹血糖(7.4±1.8)mmol/L。两组病例在上诉一般资料方面比较差异无统计学意义，(P＞0.05)，具有可比性。
1.2诊断与辨证标准 西医诊断标准：按1999年WHO诊断和分类标准进行糖尿病诊断和分型。中医辨证标准：口干多饮，神疲乏力，面色萎黄，脘腹胀满，食纳不香，肢体麻痹疼痛，以刺痛为主，夜间加重，间歇性跛行，半身不遂，舌淡暗有瘀点，苔白，脉沉细涩。
1.3纳入标准 (1)符合2型糖尿病诊断标准；(2)中医辨证主证属于脾虚络瘀可以使用健脾活络方治疗的患者。
1.4排除标准 (1)年龄不足35岁或者超过75岁者；(2)认知障碍、无完整表达能力者、不能配合治疗者。(3)伴有严重肝、肾、心、脑疾病者，或者合并糖尿病酮症等急、重者。(4)合并其他神经病变如(多发性硬化、红斑性肢痛、腰椎间盘突出症、神经根型颈椎病等)者。(5)依从性差，未按规定用药，影响临床疗效者。
2方法
2.1治疗方法 两组均给予糖尿病综合治疗，即健康教育、饮食管理、运动管理、血糖监测及管理等，口服降糖药物或应用胰岛素常规治疗。对照组口服弥可保片，每次0.5mg，3次/d。观察组加用实施例1的健脾活络方治疗，水煎服，日1剂，每日1剂，煎煮成400mL，每次200mL，早晚2次温服，治疗4周后统计治疗结果。
2.2观察指标
2.2.1安全评价标准 一般体格检查：血压、呼吸、脉搏、体温。②血尿便常规检查。
2.2.2疗效性观察 空腹及餐后2h血糖、糖化血红蛋白、TCSS评分。
2.3统计学处理 本研究中的相关数据选择统计学软件SPSS 18.0展开统计学处理，以均数±标准差表示计量资料，采用t检验，P<0.05则表示组间计数资料对比差异性较为显著，存在统计学意义。
3结果
3.1治疗前后2组患者血糖、糖化血红蛋白比较 2组患者治疗前的空腹血糖、餐后2h血糖和糖化血红蛋白比较差异没有统计学意义(P>0.05)，具有可比性。2组患者在治疗后的空腹血糖均有所下降， 治疗前后对比差异性有统计学意义(P<0.05)，治疗后健脾活络方组患者后餐后2h血糖与空腹血糖、糖化血红蛋白水平明显优于对照组患者(P<0.05)，存在统计学意义，见表1。
表1两组治疗前后空腹血糖、餐后2h血糖及糖化血红蛋白比较(n＝32)
Figure PCTCN2020124302-appb-000001
注：★与治疗前相比，P<0.05；●与对照组相比，P<0.05。
3.2治疗前后2组患者TCSS评分(多伦多临床神经病变评分)结果比较 治疗后两组患者TCSS评分较前均有明显降低，差异有统计学意义(P<0.05)，表明两组患者通过治疗症状有改善，组间比较，观察组的TCSS评分降低更显著(P<0.05)，提示观察组治疗效果比对照组更好。见表2。
表2两组治疗前后TCSS评分比较
Figure PCTCN2020124302-appb-000002
注：★与治疗前相比，P<0.05；●与对照组相比，P<0.05
3.3治疗前后2组患者不良反应比较 两组未出现肝肾功能异常，糖尿病酮症酸中毒、低血糖昏迷等急性并发症。
3.结论
糖尿病属于中医学“消渴”范畴，古代中医学多从“阴虚燥热”论治。然而,现今临床发现不论是病因病机与发病，还是临床表现，乃至治疗方法，都已发生变化。
临床实践表明，本发明的健脾活络方治疗糖尿病中后期脾虚络瘀，表现以肢体麻痹刺痛为主症的患者，不仅降糖效果确切，使用安全，而且在改善患者生活质量，减轻糖尿病引起的症状上较之西药治疗更有优势。
二、治疗糖尿病眼底病变的临床研究
1.资料与方法
1.1一般资料 全部68例为2017年1月-2019年5月汕头市中医院住院患者，按照随机数字表法分为两组。治疗组34例，男20例，女14例；年龄45～78岁，平均(56.67±6.53)岁；病程2～14年，平均(8.46±0.67)年；视网膜病变分期：Ⅰ期16例，Ⅱ期12例，Ⅲ期6例。对照组34例，男19例，女15例；年龄46～76岁，平均(56.65±6.57)岁；病程1～16年，平均(8.48±0.69)年；视网膜病变分期：Ⅰ期18例，Ⅱ期11例，Ⅲ期5例。两组一般资料比较差异无统计学意义(P ＞0.05)，具有可比性。
1.2病例选择
1.2.1诊断标准 ①参照《现代糖尿病诊断治疗学》中DR的诊断标准；②中医辨证主证属于脾虚络瘀可以使用本发明健脾活络方治疗的患者。
1.2.2纳入标准 ①近4周未使用抗凝、改善微循环药物；②无脏器功能障碍；③无药物过敏。
1.2.3排除标准 ①有视网膜手术史；②妊娠期；③未签署治疗知情同意书；④临床资料不完整或失访者；⑤合并其他原发性或继发性视网膜病变者；⑥合并血液***疾病者；⑦合并有严重心脑血管及肝肾功能损害患者，或者近期出现糖尿病酮症、高渗性昏迷及严重干扰者。
1.3治疗方法 两组均予降血糖药物治疗及运动、饮食控制等，血糖控制平稳。
1.3.1对照组 予羟苯磺酸钙胶囊(北京京丰制药集团有限公司，国药准字H20010795)0.5g，每日3次口服。
1.3.2治疗组 治疗组在对照组基础上增加中医治疗，口服实施例1的健脾活络方汤剂，日1剂。
1.3.3疗程 两组均4周为1个疗程，连续治疗2个疗程。
1.4观察指标及方法 ①清晨抽取患者空腹肘静脉血3～5mL，常规离心，取上清液，采用酶联免疫吸附测定(ELISA)法检测VEGF、Ang-1水平，采用比色法检测SOD水平。试剂盒由上海酶联生物科技有限公司提供，操作按试剂盒说明书进行。②应用全自动血流变分析仪(天津市唐宇医疗器械科技发展有限公司)检测血液流变学指标血浆黏度、全血黏度(高切)、全血黏度(中切)、全血黏度(低切)、红细胞聚集指数、红细胞刚性指数及纤维蛋白原(FIB)。
1.5疗效标准 显效：患者治疗后视力改善4行，微血管瘤、出血基本消失；有效：患者治疗后视力改善2行，微血管瘤、出血部分消失；无效：患者治疗后视力、眼底上述病变无明显变化或加重。
1.6统计学方法 采用SPSS 21.0统计软件进行数据统计分析，计量资料用均数±标准差
Figure PCTCN2020124302-appb-000003
表示，采用t检验；计数资料率的比较采用χ 2检验。P＜0.05为差异有统计学意义。
2.结果
2.1两组疗效比较 两组显效率、总有效率比较差异均有统计学意义(P＜0.05)，治疗组疗效优于对照组。见表3。
表3两组患者疗效比较[n(％)]
Figure PCTCN2020124302-appb-000004
注：与对照组比较，*P＜0.05。
2.2两组治疗前后VEGF、Ang-1及SOD比较 两组治疗4、8周后VEGF均较本组治疗前降低(P＜0.05)，Ang-1、SOD升高(P＜0.05)，且治疗组VEGF低于对照组治疗同期(P＜0.05)，Ang-1、SOD高于对照组治疗同期(P＜0.05)。见表4。
表4两组患者治疗前后VEGF、Ang-1、SOD比较(
Figure PCTCN2020124302-appb-000005
n＝68)
Figure PCTCN2020124302-appb-000006
注：与本组治疗前比较， ＊P＜0.05；与对照组治疗同期比较， #P＜0.05。
2.3两组治疗前后血液流变学指标比较 治疗组治疗4、8周后，血浆黏度、全血黏度(高切)、全血黏度(中切)、全血黏度(低切)、红细胞聚集指数、红细胞刚性指数及FIB均较本组治疗前降低(P＜0.05)，且低于对照组治疗同期(P＜0.05)。对照组治疗前后血液流变学指标比较差异无统计学意义(P＜0.05)。见表5。
表5两组患者治疗前后血流流变学指标比较(
Figure PCTCN2020124302-appb-000007
n＝68)
Figure PCTCN2020124302-appb-000008
Figure PCTCN2020124302-appb-000009
注：与本组治疗前比较， ＊P＜0.05；与对照组治疗同期比较， #P＜0.05。
3.讨论
中医学认为，DR主要是在消渴脾虚的基础上发展而成。消渴日久，气阴两虚，气虚运血无力，气虚则血瘀，瘀血阻于目络；加上患者多数年老体衰，肾精亏虚，肝血不足，精血难以上荣于目，目络失养，则视物昏渺；气虚摄血无权，均可致血溢脉外，引发出血，最终致瘀血日久不去，进一步阻滞目络而失明。正如《儒门事亲》所载“夫消渴者多变盲聋”，《证治要诀》云“三消日久，精血既亏，或目无所见”。因此，DR多属本虚标实之证，以气虚或气阴两虚为本，瘀血痰浊阻络为标，病变在脾、肝、肾，应以健脾益气、补益肝肾、活血化瘀为治则。羟苯磺酸钙是近年来研发上市的毛细血管调节药物，主要治疗微血管病、静脉曲张综合征。对微血管病变有良好作用。
微血管病变为DR发病的基本环节，表现为毛细血管无灌注区扩大，视网膜大片血管闭锁，严重缺血缺氧，最终形成新生血管，此过程有多种细胞因子参与。VEGF是一种血管内皮生长因子，其高表达可促进DR新生血管的形成，增强血管通透性，诱导内皮细胞生长，此外还促进视网膜氧化应激状态，诱导炎性反应，加重视网膜损伤。Ang-1可调节血管形成，抑制VEGF的表达及血管增殖，改善内皮细胞的稳定性。SOD可间接反映体内的抗氧化能力。随着病情的加重，视网膜组织可出现毛细血管充血扩张，致使牵拉性视网膜脱离，导致患者失明。高血糖引起眼底微循环紊乱，激活蛋白激酶C，催化激活内皮细胞一氧化氮合酶，促进促进新生血管发生。另外低血流灌注产生较多自由基，激活某些诱导凋亡的基因，加重视神经损害。
本研究结果表明，治疗组治疗4、8周后VEGF水平降低，Ang-1、SOD升高(P＜0.05)，且VEGF水平低于对照组治疗同期(P＜0.05)，Ang-1、SOD高于对照组治疗同期(P＜0.05)，提示健脾益活络方通过调节血液VEGF、Ang-1表达，从而干预视网膜微血管形成，抑制疾病进展。血液流变学指标异常也是DR的重要因素之一，由于视网膜血管细小，血浆黏度、全血黏度、红细胞聚集指数及FIB一旦增加，极易形成微血管栓子，降低视网膜耐氧能力，促进血管代偿性扩张，从而形成血管瘤，引起或加重患者病情。本研究结果表明，治疗组治疗后血浆黏度、全血黏度、红细胞聚集指数、红细胞刚性指数及FIB均低于对照组(P＜0.05)，说明健脾活络方可降低血液流变学指标水平，从而改善视网膜局部微循环，改善患者视力水平，这可能与健脾活络方具有较强的活血、化瘀作用有关。
综上所述，DR多因脾气亏虚，瘀血阻滞目络形成，本发明健脾活络方健脾益气、活血化瘀，能 显著改善DR患者血液流变学及视网膜微循环血管形成，提高视力水平，标本兼治，安全性高，值得临床推广应用。
三、治疗糖尿病周围神经病变的临床研究
1临床资料
1.1试验对象
选取2018年7月～2019年6月期间，汕头市中医医院收治的糖尿病周围神经病变(DSPN)患者80例。根据随机数表法分为治疗组和对照组，每组各40例。治疗组中，男26例，女14例；年龄45～76岁，平均(54.1±2.2)岁；病程3～20年，平均(10.5±3.2)年。对照组中，男21例，女19例；年龄43～77岁，平均(53.3±3.1)岁；病程2～19年，平均(10.1±1.3)年。2组性别、年龄、病程等一般资料比较，差异无统计学意义(P＞0.05)，具可比性。
1.2诊断标准
1.2.1西医诊断标准 参照《中国2型糖尿病防治指南(2017年版)》拟定标准。(1)明确的糖尿病病史；(2)诊断糖尿病时或之后出现的神经病变；(3)临床症状和体征与DSPN的表现相符；(4)有临床症状(疼痛、麻木、感觉异常等)者，5项检查(踝反射、针刺痛觉、温度觉、震动觉、压力觉)中任1项异常；无临床症状者，5项检查中任2项异常，临床诊断为DSPN；(5)排除以下情况：其他病因引起的神经病变，如颈腰椎病变(神经根压迫、椎管狭窄、颈腰椎退行性变)、脑梗死、格林-巴利综合征；严重动静脉血管性病变(静脉栓塞、***炎)等；药物尤其是化疗药物引起的神经毒性作用，以及肾功能不全引起的代谢毒物对神经的损伤。
1.2.2脾虚络瘀型诊断标准：(1)神疲乏力，(2)面色萎黄或黧黑，(3)脘腹胀满，(4)食纳不香，(5)肌肤甲错，(6)肢体麻痹疼痛，以刺痛为主，(7)夜间加重，(8)间歇性跛行，(9)半身不遂，(10)口角歪斜，(11)舌淡暗有瘀点，苔白，(12)脉沉细涩。凡符合上述症状7项以上者，可判定为消渴脾虚络瘀型。
1.3纳入标准
(1)年龄：18～80岁；(2)符合糖尿病诊断标准；(3)符合糖尿病DSPN的诊断标准；(4)符合以上标准基础上，中医辨证分型脾虚络瘀型。
1.4排除标准
(1)妊娠或哺乳期女性；(2)认知或沟通障碍者；(3)肝肾功能严重损害者；(4)其他***或器官严重障碍者；(5)近l个月内，有糖尿病酮症酸中毒，或严重感染者；(6)某些过敏体质，或对治疗中任意用药过敏者。
2.研究方法
2.1基础治疗：采用西医常规治疗。包括糖尿病饮食、适量运动、健康教育，口服合适的降血糖药或注 射胰岛素。血糖控制水平为空腹血糖5.0～8.0mmol/L，睡前血糖5.0～10.0mmol/L。
2.2对照组：在基础治疗的基础上，每个患者加用甲钴胺片500μg，1日3次口服。
2.3治疗组：在对照组处理的基础上，每个患者加用实施例1组方，煎煮成400mL，每次200mL，早晚2次温服。
2.4治疗8周后统计治疗结果。
3.观察指标
3.1 TCSS评分包括神经症状、反射及感觉评分：(1)症状：下肢麻木或无知觉、疼痛(烧灼痛或电击样痛)、乏力、针刺样感觉、行走不稳，并询问上肢是否有相似症状。无异常计0分，一个症状计1分，共6分；(2)反射：踝、膝反射，共8分，无异常计0分，一侧减弱为1分，消失为2分；(3)感觉：检查右拇指的痛觉、振动觉、位置觉、触觉和温度觉5项内容，无异常计0分，一个症状为1分，共5分。3项检查总分19分。
3.2震动感觉阈值(VPT)检查-足部感觉神经：让患者平卧，连接振动感觉测定仪于患者第一足趾基部和足背，随着电流增强，震动仪的震幅会随之增大，患者感知到震动的伏特数，为检查结果，3次测量，取平均值。参考范围：病变临界区域10-15V，轻度-中度病变16-24V，严重病变>25V。
3.3参考《糖尿病周围神经病变的临床疗效评定标准归类及分析》对3组患者治疗后的疗效进行判定：(1)显效：无自觉症状，膝腱反射基本正常，VPT检查结果正常；(2)有效：自觉症状、膝腱反射好转明显，VPT检查结果有改善；(3)无效：自觉症状、膝腱反射及VPT检查结果无改变。总有效率为显效和有效例数之和/总例数乘以100％。
3.4生活质量测评：测评量表参考生活质量简易量表SF-36，该量表由世界卫生组织(WHO)批准，信度可靠。量表包含8个维度，涵盖生活机能和职能、躯体疼痛、精力、一般健康状况、情感及心理健康情况等方面。各维度分别计分再累加，此为原始分数，再通过标准公式转换为总均分，分值0到100，分数越高生活质量越好。
3.5.统计学分析
数据资料以SPSS20.0统计分析。计数资料采用χ2检验，等级资料采用秩和检验。计量资料以
Figure PCTCN2020124302-appb-000010
表示，组内治疗前后比较，符合正态分布则采用配对t检验，不符合则用秩和检验；2组间比较，符合正态分布且方差齐时，用t检验，不符合时用秩和检验。以P＜0.05为差异有统计学意义。
4结果
4.1 2组患者TCSS评分对比 治疗前2组患者TCSS评分基线均衡(P>0.05)；治疗后，2组TCSS评分均较治疗前明显降低(P<0.05)，组间比较具有统计学差异(P<0.05)，见表6。
表6对比2组患者TCSS评分
Figure PCTCN2020124302-appb-000011
Figure PCTCN2020124302-appb-000012
注:与治疗前对比， aP<0.05；与对照组对比， bP<0.05。
4.2 2组患者VPT检查结果对比 治疗前2组患者VPT检查结果对比差异不明显(P>0.05)；治疗后，2组VPT检查结果均明显降低(P<0.05)，2组之间对比差异明显(P<0.05)，见表7。
表7对比2组患者VPT检查结果[
Figure PCTCN2020124302-appb-000013
n＝40]
Figure PCTCN2020124302-appb-000014
注:与治疗前对比， aP<0.05；与对照组对比， bP<0.05。
4.3 2组患者疗效对比 治疗后观察组总有效率87.50％，对照组62.50％，2组对比差异明显(P<0.05)，见表8。
表8对比3组患者疗效[n(％)]
Figure PCTCN2020124302-appb-000015
注:与对照组对比， aP<0.05。
4.4 2组患者生活质量对比 治疗前，2组生活质量SF-36各维度总均分对比差异不明显(P>0.05)；治疗后，2组生活质量SF-36各维度总均分均改善明显(P<0.05)，2组之间对比差异明显(P<0.05)，见表9。
表9对比2组生活质量[
Figure PCTCN2020124302-appb-000016
n＝40]
Figure PCTCN2020124302-appb-000017
注:与治疗前对比， aP<0.05；与对照组对比， bP<0.05。
4.5 2组患者不良反应对比 两组未出现肝肾功能异常，及糖尿病酮症酸中毒、低血糖昏迷等急性并发症。对照组40例患者，1例出现轻微头晕，未经停药治疗，症状自行减轻。
5讨论
震动感觉阈值(VPT)检查-足部感觉神经是诊断糖尿病周围神经病变的特异性指标，是临床常用评价糖尿病周围神经病变及治疗效果的标准。本研究结果显示，经过治疗前后的对比及组间的对比，健脾活络方可以明显改糖尿病周围神经病变患者的临床症状，提高临床疗效，使患者生活质量得到改善，增强患者的治疗信心，且无明显不良反应，简便易行，可操作性强，值得临床推广应用。
四、治疗脾虚络瘀型的糖尿病周围血管病变的临床研究
1临床资料
1.1试验对象
选取2018年7月～2019年6月期间，汕头市中医医院收治的糖尿病周围血管病变患者90例。根据随机数表法分为治疗组和对照组，每组各45例。治疗组中，男31例，女19例；年龄45～77岁，平均(54.1±2.1)岁；病程3～19年，平均(10.4±3.2)年。对照组中，男26例，女24例；年龄42～75岁，平均(53.2±3.0)岁；病程2～21年，平均(10.1±1.4)年。2组性别、年龄、病程等一般资料比较，差异无统计学意义(P＞0.05)，具可比性。
1.2诊断标准
1.2.1西医诊断标准 2017年《中国2型糖尿病防治指南》拟定。(1)临床确诊为糖尿病的患者。(2)有下肢动脉硬化闭塞缺血的临床表现。(3)ABI检查：ABI≤0.90可诊断为下肢缺血。(4)颈动脉彩超：提示动脉硬化、斑块、管腔狭窄等。(5)周围血管CTA、MRA或DSA：提示管腔狭窄等。
1.2.2脾虚络瘀型诊断标准：(1)神疲乏力，(2)面色萎黄或黧黑，(3)脘腹胀满，(4)食纳不香，(5)肌肤甲错，(6)肢体麻痹疼痛，以刺痛为主，(7)夜间加重，(8)间歇性跛行，(9)半身不遂，(10)口角歪斜，(11)舌淡暗有瘀点，苔白，(12)脉沉细涩。凡符合上述症状7项以上者，可判定为消渴痹证脾虚络瘀型。
1.3纳入标准
(1)年龄：18～80岁；(2)符合糖尿病诊断标准；(3)符合糖尿病周围血管病变的诊断标准；(4)符合以上标准基础上，中医辨证分型脾虚络瘀型。
1.4排除标准
(1)妊娠或哺乳期女性；(2)认知或沟通障碍者；(3)肝肾功能严重损害者；(4)其他***或器官严重障碍者；(5)近l个月内，有糖尿病酮症酸中毒，或严重感染者；(6)某些过敏体质，或对治疗中任意用药过敏者。患者均知情同意，并签署协议。
2.研究方法
2.1基础治疗：采用西医常规治疗。包括糖尿病饮食、适量运动、健康教育，口服合适的降血糖药或注射胰岛素。血糖控制水平为空腹血糖5.0～8.0mmol/L，睡前血糖5.0～10.0mmol/L。
2.2对照组：在基础治疗的基础上，每个患者加用阿司匹林肠溶片100mg qn，阿托伐他汀钙20mg qn口服。
2.3治疗组：在对照组处理的基础上，每个患者加用实施例1组方，煎煮成400mL，每次200mL，早晚2次温服。
2.4治疗8周后统计治疗结果。
3.观察指标
3.1颈动脉血管内膜中层厚度(CIMT):采用彩色多普勒超声诊断仪检测患者治疗前与治疗前后颈动脉的IMT。
3.2 ABI评价方法 参考《下肢动脉硬化闭塞症诊治指南》(2015年)。(1)ABI计算方法：踝部动脉(胫后动脉或足背动脉)收缩压与上臂收缩压(取左右手臂数值高的一侧)的比值。(2)ABI评价方法：正常范围：1.00～1.40；临界范围：0.91～0.99；下肢缺血：≦0.9。
3.3疗效进行判定 (1)临床痊愈：临床症状、体征消失或基本消失，症候疗效指数≥90％；或ABI恢复至正常范围。(2)显效：临床症状、体征明显改善，症候疗效指数≥70％且＜90％；或ABI恢复至临界值。(3)有效：临床症状、体征有好转，症候疗效指数≥30％且＜70％；或ABI较治疗前改善。(4)无效：临床症状、体征无明显改善，甚或加重，症候疗效指数＜30％；或ABI较治疗前无改善。
注：症候疗效指数＝(治疗前积分-治疗后积分)/治疗前积分×100％。若症候疗效与ABI疗效不一致时，以疗效好者为准。
3.4.统计学分析
数据资料以SPSS20.0统计分析。计数资料采用χ2检验，等级资料采用秩和检验。计量资料以
Figure PCTCN2020124302-appb-000018
表示，组内治疗前后比较，符合正态分布则采用配对t检验，不符合则用秩和检验；2组间比较，符合正态分布且方差齐时，用t检验，不符合时用秩和检验。以P＜0.05为差异有统计学意义。
4结果
4.1 2组患者CIMT对比 治疗前2组患者CIMT基线均衡(P>0.05)；治疗后，观察组CIMT均较治疗前明显降低(P<0.05)，组间比较具有统计学差异(P<0.05)，见表10。
表10对比2组患者CIMT(mm)[
Figure PCTCN2020124302-appb-000019
n＝40]
Figure PCTCN2020124302-appb-000020
注:与治疗前对比， aP<0.05；与对照组对比， bP<0.05。
4.2 2组患者ABI检查结果对比 治疗前2组患者ABI检查结果对比差异不明显(P>0.05)；治疗后，2组VPT检查结果均明显降低(P<0.05)，2组之间对比差异明显(P<0.05)，见表11。
表11对比2组患者ABI检查结果[
Figure PCTCN2020124302-appb-000021
n＝40]
Figure PCTCN2020124302-appb-000022
注:与治疗前对比， aP<0.05；与对照组对比， bP<0.05。
4.3 2组患者疗效对比 治疗后观察组总有效率87.50％，对照组62.50％，2组对比差异明显(P<0.05)，见表12。
表12对比2组患者疗效[n(％)]
Figure PCTCN2020124302-appb-000023
注:与对照组对比， aP<0.05。
4.5 2组患者不良反应对比 两组未出现肝肾功能异常，及糖尿病酮症酸中毒、低血糖昏迷等急性并发症。
5讨论
本研究结果显示，经过治疗前后的对比及组间的对比，本发明健脾活络方可以明显改糖尿病周围血管病变患者的临床症状，提高临床疗效，使患者生活质量得到改善，增强患者的治疗信心，且无明显不良反应，简便易行，可操作性强，值得临床推广应用。
五、治疗糖尿病合并冠心病的临床研究
糖尿病患者以血糖异常升高导致血液黏稠和血流速度减慢为主要特征，可引发心血管疾病等严重并发症。冠心病为糖尿病常见心血管并发症，以心肌冠脉粥样硬化和管腔狭窄导致心肌缺血缺氧为主要特征。近年来，我国老龄化趋势加快，加上饮食结构变化，糖尿病合并冠心病发病率逐年升高，需及时治疗，改善患者预后。发明人应用健脾活络方治疗糖尿病合并冠心病，取得较好疗效，总结如下：
1资料与方法
1.1一般资料
此次研究纳入的对象来源于2018年12月～2019年12月汕头市中医医院收治糖尿病合并冠心病患者中随机抽取的83例。所有患者符合冠心病、糖尿病诊断标准，均知情同意本次研究。将上述83例糖尿病合并冠心病患者随机分为对照组41例和治疗组42例。治疗组患者男27例，女15例；年龄37～80岁，平均年龄(49.34±11.13)岁。病程5个月～5年，平均病程(2.51±0.21)年；体重42kg～78kg，平均体重(57.31±8.25)kg。对照组患者男27例，女14例；年龄37～79岁，平均年龄(49.10±11.53)岁。病程5个月～5年，平均病程(2.56±0.25)年；体重42kg～78kg，平均体重为(57.92±8.45)kg。两组患者一般资料，差异具有统计学意义P＞0.05，具有可比性。
1.2诊断与辨证标准 西医诊断标准：糖尿病按1999年WHO诊断和分类标准进行糖尿病诊断和分型；冠心病按2007年《慢性稳定性心绞痛诊断与治疗指南》的诊断标准进行诊断。
中医辨证标准：口干多饮，胸闷或胸痛，神疲乏力，面色萎黄，脘腹胀满，食纳不香，肢体麻痹疼痛，以刺痛为主，夜间加重，间歇性跛行，半身不遂，舌淡暗有瘀点，苔白，脉沉细涩。
1.3纳入标准 (1)符合2型糖尿病及冠心病诊断标准；(2)中医辨证主证属于脾虚络瘀可以使用健脾活络方治疗的患者。
1.4排除标准 (1)年龄不足35岁或者超过80岁者；(2)认知障碍、无完整表达能力者、不能配合治疗者。(3)合并糖尿病酮症、糖尿病酮症酸中毒、重度高血压，重度心律失常，重度心肺功能不全，肿瘤，或肝、肾、脑、造血***等严重原发性疾病的患者。(4)经完善检查后证实为急性心肌梗塞或其他心脏疾病、颈椎病、甲亢、胃及食管反流、胆心病、重度神经官能症、更年期症候群等导致的胸 闷痛。(5)依从性差，未按规定用药，影响临床疗效者。
1.5方法
对照组给予西医常规治疗，给予降糖药物口服或胰岛素注射，控制血糖水平为3.9～7.8mmol/L，并给予辛伐他汀调脂稳斑，同时结合常规饮食指导和运动指导。
治疗组在对照组基础上增加中医治疗，口服本发明实施例1汤剂(以下称健脾活络方)，日1剂。
两组均治疗1个月。
1.6观察指标和标准
比较两组患者(1)糖尿病合并冠心病治疗总有效率；(2)干预前和干预后患者空腹血糖、E/A、血浆黏度、红细胞聚集指数的差异。
显效：经治疗，患者心绞痛发作次数减少＞80％，发作持续时间明显缩短，疼痛明显减轻，心电图和血糖水平正常；有效：经治疗，患者心绞痛发作次数减少＞50％，发作持续时间有所缩短，疼痛减轻，心电图和血糖水平改善；无效：达不到上述标准。糖尿病合并冠心病治疗总有效率＝显效率+有效率。
1.4统计学处理方法
SPSS 21.0软件统计糖尿病合并冠心病患者数据，计数资料采取χ 2检验，计量资料采取t检验。以P＜0.05为差异具有统计学意义。
2结果
2.1两组患者糖尿病合并冠心病治疗总有效率相比较
治疗组较之对照组糖尿病合并冠心病治疗总有效率更高，差异具有统计学意义(P＜0.05)，见表13。
表13两组患者糖尿病合并冠心病治疗总有效率相比较[n(％)]
Figure PCTCN2020124302-appb-000024
注：与对照组比较，P＜0.05。
2.2干预前和干预后空腹血糖、E/A、血浆黏度、红细胞聚集指数相比较
干预前两组空腹血糖、E/A、血浆黏度、红细胞聚集指数相似，差异无统计学意义(P＞0.05)；干预后治疗组较之对照组空腹血糖、E/A、血浆黏度、红细胞聚集指数改善更显著，差异具有统计学意义(P＜0.05)。见表14。
表14干预前和干预后空腹血糖、E/A、血浆黏度、红细胞聚集指数相比较
Figure PCTCN2020124302-appb-000025
Figure PCTCN2020124302-appb-000026
Figure PCTCN2020124302-appb-000027
注：与干预前相比较，#表示P＜0.05；与对照组干预后相比较，*表示P＜0.05。
3讨论
经研究，结果显示，治疗组较之对照组糖尿病合并冠心病治疗总有效率更高，空腹血糖、E/A、血浆黏度、红细胞聚集指数改善更显著，说明本发明健脾活络方治疗糖尿病合并冠心病疗效确切，可有效改善患者血糖和心功能，改善血流动力学，对患者预后有益，值得推广。
六、治疗糖尿病合并脑梗塞的临床研究
糖尿病比较容易出现大血管病变，其中合并脑梗死是比较严重的一种并发症，该病以腔隙梗死、小动脉梗死、中动脉梗死为主要特点，具有较高的发病率和复发率。发明人应用健脾活络方治疗糖尿病合并冠心病，取得较好疗效，总结如下：
1资料和方法
1.1一般资料 汕头市中医医院2018年1月～2019年12月期间收治的60例2型糖尿病合并脑梗死患者随机分为两组。对照组17例为男性，13例为女性，年龄40～75岁，平均年龄为(59.7±12.3)岁，糖尿病病程2～31年，平均病程为(15.6±5.8)年，脑梗死部位：8例为顶叶梗死，13例为基底节梗死，2例为多发性脑梗死，7例为额叶梗死；观察组18例为男性，12例为女性，年龄42～77岁，平均年龄为(60.6±12.9)岁，病程1～30年，平均病程为(16.1±5.9)年，脑梗死部位：6例为顶叶梗死，15例为基底节梗死，3例为多发性脑梗死，6例为额叶梗死。两组患者在年龄、性别以及病程等一般资料方面，无显著差异。
1.2方法 临床上对照组患者常规治疗，即降低颅内压、降脂以及控制血糖等对症治疗，并对患者的血糖进行密切监测。观察组在对照组治疗的基础上给予实施例1汤剂，水煎服，日1剂，早晚2次温服。1个疗程为1月。
1.3疗效判定标准 应用反映神经功能的美国国立卫生研究院卒中量表(NIHSS)评分进行评分，(1)基本痊愈：临床症状完全消失，神经功能缺损评分较治疗前减少91％～100％，病残程度0级；(2)显效：临床症状明显改善，神经功能缺损程度较治疗前减少46％～90％，病残程度1～3级；(3)有效：临床症状有所缓解，神经功能缺损评分较治疗前减少18％～45％；(4)无效：临床症状没有出现任何变化，神经功能缺损评分较治疗前减少＜18％，甚至病情进一步发展恶化。
2结果
2.1两组临床治疗效果对比 经过1个疗程治疗，无1例患者死亡，均顺利完成治疗，见表15
表15两组临床治疗效果对比[n(％)]
Figure PCTCN2020124302-appb-000028
两组相比*P＜0.05。
2.2两组不良反应对比 治疗期间，观察组1例患者出现恶心、呕吐；1例患者腹泻，不良反应发生率为6.7％，而对照组3例患者出现恶心、呕吐，2例患者腹泻，不良反应发生率为16.7％(P＜0.05)。两者患者无1例患者出现肝肾损害、药物过敏等严重不良反应，所有患者经对症治疗后缓解，不影响治疗效果。
3讨论
本次研究结果显示，观察组的治疗总有效率为90％，而对照组的治疗总有效率为70％，可见健脾活络方改善神经功能效果显著，并且比较对照组而言，观察组的不良反应发生率低，所以值得临床上进一步研究推广。

Claims (8)

  1. 一种健脾活络中药组合物，其特征在于：按重量份数计算，配方由以下组分组成：葛根15-25份、丹参12-18份、白术25-35份、党参25-35份、黄柏8-12份、石菖蒲8-12份、地龙12-18份、川芎8-12份、黄芪25-35份、田七8-12份。
  2. 根据权利要求1所述的健脾活络中药组合物，其特征在于：按重量份数计算，配方由以下组分组成：葛根18-22份、丹参14-16份、白术28-32份、党参28-32份、黄柏9-11份、石菖蒲9-11份、地龙14-16份、川芎9-11份、黄芪28-32份、田七9-11份。
  3. 根据权利要求1所述的健脾活络中药组合物，其特征在于：按重量份数计算，配方由以下组分组成：葛根20份、丹参15份、白术30份、党参30份、黄柏10份、石菖蒲10份、地龙15份、川芎10份、黄芪30份、田七10份。
  4. 权利要求1-3任一权利要求所述健脾活络中药组合物在制备治疗糖尿病、糖尿病周围神经病变、糖尿病周围血管病、糖尿病眼底病变、糖尿病合并冠心病或糖尿病合并脑梗塞的药物的应用。
  5. 根据权利要求4所述的应用，其特征在于：所述的药物为汤剂、颗粒剂、片剂、胶囊剂、口服液或丸剂。
  6. 根据权利要求4所述的应用，其特征在于：所述的药物为以所述健脾活络中药组合物配方中组分的提取物为有效成分，添加药用辅料制得的制剂。
  7. 根据权利要求6所述的应用，其特征在于：所述的提取物为水提取物。
  8. 根据权利要求4所述的应用，其特征在于：所述的糖尿病、糖尿病周围神经病变、糖尿病周围血管病、糖尿病眼底病变、糖尿病合并冠心病或糖尿病合并脑梗塞是脾虚络瘀型的糖尿病后期、糖尿病周围神经病变、糖尿病周围血管病、糖尿病眼底病变、糖尿病合并冠心病或糖尿病合并脑梗塞。
PCT/CN2020/124302 2020-07-29 2020-10-28 一种健脾活络中药组合物及其应用 WO2022021636A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010744301.0A CN111643586A (zh) 2020-07-29 2020-07-29 一种健脾活络中药组合物及其应用
CN202010744301.0 2020-07-29

Publications (1)

Publication Number Publication Date
WO2022021636A1 true WO2022021636A1 (zh) 2022-02-03

Family

ID=72346400

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/124302 WO2022021636A1 (zh) 2020-07-29 2020-10-28 一种健脾活络中药组合物及其应用

Country Status (2)

Country Link
CN (1) CN111643586A (zh)
WO (1) WO2022021636A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115252700A (zh) * 2022-07-27 2022-11-01 佛山市高明区人民医院 用于治疗颈源性耳鸣的中药组合物、药物及其制备方法
CN116920047A (zh) * 2023-05-31 2023-10-24 江苏省中医药研究院 一种新型冠状病毒感染相关心肌损伤的中药复方组合物及制备方法

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111643586A (zh) * 2020-07-29 2020-09-11 汕头市中医医院 一种健脾活络中药组合物及其应用
CN113694130A (zh) * 2021-09-26 2021-11-26 辽宁中医药大学 一种用于治疗糖尿病性心脏病变的中药组合物及制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102631595A (zh) * 2012-05-15 2012-08-15 云南中医学院 治疗2型糖尿病的药物及其制备方法
CN111643586A (zh) * 2020-07-29 2020-09-11 汕头市中医医院 一种健脾活络中药组合物及其应用
CN111658701A (zh) * 2020-07-14 2020-09-15 汕头市中医医院 一种健脾中药组合物及其应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102631595A (zh) * 2012-05-15 2012-08-15 云南中医学院 治疗2型糖尿病的药物及其制备方法
CN111658701A (zh) * 2020-07-14 2020-09-15 汕头市中医医院 一种健脾中药组合物及其应用
CN111643586A (zh) * 2020-07-29 2020-09-11 汕头市中医医院 一种健脾活络中药组合物及其应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEN QIUMING, CHEN CHAO, WU BANGTAI: "Clinical Application of Spleen and Stomach Theory for Diabetes Treatment", GUANGMING-ZHONGYI = GUANGMING JOURNAL OF CHINESE MEDICINE, ZHONGHUA ZHONGYIYAO XUEHUI ZHUBAN. GUANGMING-ZHONGYI ZAZHE BIANJIBU BIANJI, CN, vol. 34, no. 23, 31 December 2019 (2019-12-31), CN , pages 3556 - 3558, XP055886773, ISSN: 1003-8914, DOI: 10.3969/j.issn.1003-8914.2019.23.009 *
CHU YONGXIN: "Buyang Huanwu Decoction in Treating Diabetic Complications", WORLD CHINESE MEDICINE, vol. 3, no. 1, 16 January 2008 (2008-01-16), pages 36 - 37, XP055891290 *
WANG XUHUANG, GUO YUAN-YUAN;XIE XI;WU BANG-TAI;XU XU-YUN;JI SHU-PING;GU JIE-MIN;CHEN CHAO: "Effect of Jianpi Huoluo Formula on Treating Diabetic Distal Symmetric Polyneuropathy Differentiated by Spleen Deficiency and Blood Stasis", WORLD JOURNAL OF INTEGRATED TRADITIONAL AND WESTERN MEDICINE, vol. 15, no. 3, 31 March 2020 (2020-03-31), pages 535 - 538, XP055891285, DOI: 10.13935/j.cnki.sjzx.200332 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115252700A (zh) * 2022-07-27 2022-11-01 佛山市高明区人民医院 用于治疗颈源性耳鸣的中药组合物、药物及其制备方法
CN115252700B (zh) * 2022-07-27 2023-07-11 佛山市高明区人民医院 用于治疗颈源性耳鸣的中药组合物、药物及其制备方法
CN116920047A (zh) * 2023-05-31 2023-10-24 江苏省中医药研究院 一种新型冠状病毒感染相关心肌损伤的中药复方组合物及制备方法
CN116920047B (zh) * 2023-05-31 2024-05-28 江苏省中医药研究院 一种新型冠状病毒感染相关心肌损伤的中药复方组合物及制备方法

Also Published As

Publication number Publication date
CN111643586A (zh) 2020-09-11

Similar Documents

Publication Publication Date Title
WO2022021636A1 (zh) 一种健脾活络中药组合物及其应用
WO2022011880A1 (zh) 一种健脾中药组合物及其应用
WO2022021637A1 (zh) 一种健脾益肾中药组合物及其应用
WO2022021639A1 (zh) 一种健脾通阳中药组合物及其应用
CN103751714A (zh) 一种治疗气滞血瘀型高脂血症的中药制备方法
CN115054665B (zh) 一种治疗阴囊湿疹的中药组合物
CN101897933A (zh) 一种治疗白癜风的中成药
CN115252753A (zh) 治疗失眠的中药组合物及其应用
WO2022021638A1 (zh) 一种健脾化浊中药组合物及其应用
CN110448665A (zh) 一种解酒醒酒的中药组合物及其制备方法
CN104998158A (zh) 一种治疗肝硬化的药物组合物及其应用
CN116672377B (zh) 一种治疗心力衰竭、防治虚弱状态及心衰失代偿发作的中药组合物及其制备方法
CN117122644B (zh) 治疗冠心病心绞痛和颈动脉斑块的中药组合物及其应用
CN115957265B (zh) 一种治疗虚火上炎的中药外治膏剂及其制备方法和应用
CN106728828A (zh) 一种治疗冠心病的中药制剂及其制备工艺
He Clinical Study on the Effect of Acupuncture and Moxibustion with the Method of Acupoints on the Treatment of Chronic Gastritis with Sleep Disorder
CN105031023A (zh) 一种治疗肝硬化门静脉高压症的中药组合物
CN105213975A (zh) 一种治疗肝硬化的药物组合物及其应用
CN117018105A (zh) 一种治疗糖耐量减低的中药组合物及其制备方法
CN104116794B (zh) 一种辅助治疗肥胖相关性高血压病的中药
CN116549520A (zh) 一种气血双补、清肺止咳的中药组方、中药液和药物制剂
CN116983365A (zh) 一种治疗气阴两虚证慢性萎缩性胃炎的中药组合物、制剂和应用
CN103751593A (zh) 一种治疗心肾阴虚型高脂血症的中药制备方法
CN109793828A (zh) 一种用于治疗原发性血小板增多症的中药组合物及其制备方法和应用
CN103751712A (zh) 一种治疗心血瘀阻型高脂血症的中药制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20947503

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20947503

Country of ref document: EP

Kind code of ref document: A1