WO2021051262A1 - 一种用于制备治疗水肿药物的中药组合物 - Google Patents

一种用于制备治疗水肿药物的中药组合物 Download PDF

Info

Publication number
WO2021051262A1
WO2021051262A1 PCT/CN2019/106121 CN2019106121W WO2021051262A1 WO 2021051262 A1 WO2021051262 A1 WO 2021051262A1 CN 2019106121 W CN2019106121 W CN 2019106121W WO 2021051262 A1 WO2021051262 A1 WO 2021051262A1
Authority
WO
WIPO (PCT)
Prior art keywords
edema
chinese medicine
traditional chinese
medicine composition
use according
Prior art date
Application number
PCT/CN2019/106121
Other languages
English (en)
French (fr)
Inventor
隋华芹
杨本官
赵伟
Original Assignee
鲁南制药集团股份有限公司
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 鲁南制药集团股份有限公司 filed Critical 鲁南制药集团股份有限公司
Priority to PCT/CN2019/106121 priority Critical patent/WO2021051262A1/zh
Priority to CN201980031448.0A priority patent/CN114450021B/zh
Publication of WO2021051262A1 publication Critical patent/WO2021051262A1/zh

Links

Classifications

    • 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
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
    • 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)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics

Definitions

  • the invention relates to a new use of a traditional Chinese medicine composition, in particular to the use of the traditional Chinese medicine composition in preparing a medicine for treating edema, and belongs to the technical field of traditional Chinese medicine.
  • Edema refers to the swelling of tissues caused by excessive fluid accumulation in the interstices of the human body. According to the scope of distribution, edema can be manifested as local or systemic edema. According to the degree of edema, it can be divided into mild, moderate and severe edema. Mild edema is only seen in the eyelids, infraorbital soft tissues, and the subcutaneous tissues of the anterior tibia and ankles. After acupressure, the tissues can be slightly depressed and the weight can increase by about 5%. Moderate: There may be visible edema in the loose tissues of the whole body, obvious or deep tissue depression may appear after acupressure, and the recovery will be slow. Severe: Severe edema of the whole body tissues, low-hanging skin, tight and shiny skin, and even fluid leakage, sometimes accompanied by effusion in the thoracic cavity, abdominal cavity, and hydrocele cavity.
  • the mechanism of edema mainly includes the imbalance of fluid exchange inside and outside the body and the imbalance of fluid inside and outside the blood vessel.
  • the main cause of the imbalance of fluid exchange between the body and the outside is the imbalance between glomerular filtration function and renal tubular reabsorption, leading to sodium and water retention and increased extracellular fluid volume, including decreased glomerular filtration rate and renal blood Flow redistribution, increased reabsorption of sodium in the proximal tubules, increased reabsorption of sodium in the distal tubules and collecting ducts; although the body tissue fluid is generated slightly larger than the reflux under the action of effective filtration pressure, it can maintain the intravascular and extravascular fluids through lymphatic reflux If this dynamic balance is disrupted, the fluid inside and outside the blood vessel will be imbalanced, resulting in edema.
  • the main reasons for disrupting this dynamic balance are the decrease of plasma colloidal osmotic pressure, the increase of capillary hydrostatic pressure, and capillary communication. Increased permeability, obstructed lymphatic reflux, renin-angiotensin-aldosterone system assists water and sodium retention.
  • the treatment of edema mainly adopts treatment, symptomatic treatment, restriction of water and sodium intake, and strict monitoring of fluid intake and output.
  • the medical treatment of edema is mainly western medicine, and the main medicines are diuretics, dehydrating drugs, plasma products and albumin.
  • diuretics and other drugs can excrete excessive body fluids in a short period of time, long-term use of diuretics can often cause adverse reactions such as electrolyte and fluid balance in the body, decreased blood pressure, metabolic disorders, and impaired glucose tolerance.
  • edema refers to the feeling of exogenous pathogens, eating disorders or excessive fatigue, causing lung disorders, loss of spleen transmission, kidney loss, and unfavorable opening and closing of the bladder, resulting in water retention in the body, overflowing the skin, and showing head and face.
  • the main clinical manifestations are the swelling of the eyelids, limbs, abdomen and back and even the whole body.
  • the formation of edema is related to wind attack on the surface, external feeling of dampness, improper diet, physical weakness and fatigue. Edema is located in the lungs, spleen, and kidneys, and Guan Jian is located in the kidneys.
  • the etiology is mostly wind evil, water dampness, sore toxin, and blood stasis.
  • the pathogenesis is characterized by dysfunction of the lung, loss of transmission of the spleen, loss of opening and closing of the kidney, retention of water and fluid, and overflowing into swelling. Diseases always belong to the deficiency of the essence, and the difference between yin and yang, and the two can be transformed into each other under certain conditions.
  • TCM treatment of edema adopts a combination of treatment and conditioning, which has the advantages of obvious improvement of symptoms, hydration, swelling, slowing and stability, and fewer adverse reactions.
  • the use of Chinese medicine to treat edema can not only relieve swelling and restore organ function, but also help control the development of the disease, avoid damage to the organs, and avoid the adverse reactions caused by hormone therapy.
  • Chinese patent CN100453105C discloses a composition with laxative detoxification, weight loss and lipid-lowering functions and a preparation method.
  • the composition is a traditional Chinese medicine formula consisting of Polygonum multiflorum, aloe vera, cassia, medlar, donkey-hide gelatin, ginseng, atractylodes macrocephala, and Zhishi eight flavors, and has a good therapeutic effect on constipation caused by internal poisoning and yin deficiency.
  • Related products are already on the market, and the product name is "Shouhui Laxative Capsules.”
  • the present invention is a new use of a traditional Chinese medicine composition developed on the basis of the Chinese invention patent CN100453105C in the treatment of edema.
  • the traditional Chinese medicine composition of the present invention is mainly prepared from Citrus aurantium, Atractylodes macrocephala, ginseng, wolfberry, donkey-hide gelatin, Polygonum multiflorum, cassia seed, and aloe.
  • the components of the traditional Chinese medicine composition are calculated in parts by weight:
  • the components of the traditional Chinese medicine composition are calculated in parts by weight:
  • each component in the above-mentioned traditional Chinese medicine composition is calculated in parts by weight:
  • each component in the above-mentioned traditional Chinese medicine composition is calculated in parts by weight as follows:
  • the spleen governs transportation and chemistry, including Yunhua Shuigu and Yunhua Shuiye.
  • the spleen has the function of absorbing and distributing water to prevent the water from stagnating in the body.
  • the water ingested by the human body needs to be absorbed and transformed by the spleen to spread throughout the body and play a nourishing and moisturizing effect; at the same time, the spleen transfers the excess water from various tissues and organs to the lungs and kidneys in a timely manner. , Through the gasification of the lungs and kidneys, it turns into sweat and urine and is excreted from the body.
  • the spleen has a strong function of transporting and transforming water, which can not only fully nourish the body's various tissues and organs, but also prevent the water from staying abnormally in the body, thereby maintaining the relative balance of human body's water metabolism. Conversely, if the spleen is a functional market for transporting and transforming water, the water cannot spread and stagnate in the body, and edema can occur.
  • Citrus aurantium and Atractylodes macrocephala are the master medicines, and the two are the same in the spleen meridian, which can dry dampness and diure water, invigorate the spleen and replenish qi. The two are used in combination to take the effects of drying dampness, strengthening the spleen, diuresis and reducing swelling, and quickly discharge the retained water in the body.
  • the normal metabolism of water is closely related to the normal function of the five internal organs and the balance of yin and yang. Both yin and yang are needed, especially yang qi. Yang vigorously transforms into gas, while gasification will transform water into its own accord.
  • the kidney division opens and closes, the main water is dirty.
  • the spleen controls the transportation and transformation of water and is the hub of water metabolism.
  • the lung is the main source of water and the source of water.
  • the liver controls the flow of excretion, regulates the qi machine, and when the qi moves, the water moves.
  • the heart governs the blood, and the blood is transported to facilitate water transport.
  • the turbid ones will be sent to the bladder through the opening and closing of the kidney qi and be excreted from the body. If a certain organ has a problem during the water metabolism, it will inevitably cause the water to stay in the body, causing edema and edema. Therefore, the prescription uses Polygonum multiflorum, ginseng, and donkey-hide gelatin as minister medicine, ginseng belongs to the spleen, lung, heart, and kidney meridians, Polygonum multiflorum belongs to the liver, heart, and kidney meridians, and donkey-hide gelatin belongs to the lung, liver, and kidney meridians. Triple energizer makes the water channel unblocked and maintains the water-liquid balance in the body.
  • Cassia seed and aloe vera are used as adjuvants, both of which belong to the liver and the large intestine meridian.
  • the liver regulates the flow of blood, regulates the qi machine, and promotes the metabolism of water in the body.
  • the large intestine discharges the dross. , Can take away the residual water, is a way of body fluid excretion, can eliminate edema.
  • the edema in the present invention includes generalized edema and localized edema.
  • the aforementioned systemic edema includes cardiogenic edema, renal edema, hepatogenic edema, dystrophic edema, and drug-induced edema.
  • the above-mentioned localized edema refers to edema caused by local venous and lymphatic drainage obstruction or increased capillary permeability.
  • the present invention also provides a preparation method of the above-mentioned traditional Chinese medicine composition, and the preparation steps are as follows:
  • the traditional Chinese medicine composition prepared by the above steps is directly or by adding pharmaceutically acceptable excipients to prepare clinically acceptable dosage forms, such as oral pharmaceutical preparations, through conventional procedures.
  • the oral pharmaceutical preparation is a clinically conventional oral dosage form such as pills, granules, capsules, tablets, oral liquids or syrups.
  • the oral pharmaceutical preparation is a capsule.
  • rats with yang-deficiency and edema, cGMP, Cre, BUN significantly decreased, T4, cAMP, cAMP/cGMP significantly increased, indicating that the rat thyroid axis function can be better restored, the symptoms of yang-deficiency alleviated, kidney
  • the function is restored, the state of yang deficiency is relieved, the urine protein content is significantly reduced, and the state of edema is relieved.
  • the prescription is:
  • step (2) Combine the filtrate I obtained in step (2) with the filtrate II obtained in step (3), concentrate to a thick paste with a relative density of 1.30 to 1.35 (70°C), dry, crush, and add the donkey-hide gelatin prepared in step (1) Fine powder, that is, a traditional Chinese medicine composition.
  • the obtained traditional Chinese medicine composition is prepared into a pill through a conventional pill process.
  • the prescription is:
  • the preparation method is as follows: same as the preparation method described in Example 1.
  • the obtained traditional Chinese medicine composition is prepared into a syrup according to a conventional syrup preparation process.
  • the prescription is:
  • the preparation method of the traditional Chinese medicine composition the same as the preparation method described in Example 1.
  • the obtained traditional Chinese medicine composition is prepared into granules according to the conventional granule preparation process.
  • the prescription is:
  • the preparation method of the traditional Chinese medicine composition the same as the preparation method described in Example 1.
  • the obtained traditional Chinese medicine composition is prepared into an oral liquid according to a conventional oral liquid preparation process.
  • the prescription is:
  • the preparation method of the traditional Chinese medicine composition the same as the preparation method described in Example 1.
  • the obtained traditional Chinese medicine composition is prepared into a capsule according to the conventional capsule preparation process.
  • the prescription is:
  • Citrus aurantium 120g Atractylodes macrocephala 30g Aloe 120g
  • the preparation method of the traditional Chinese medicine composition the same as the preparation method described in Example 1.
  • the obtained traditional Chinese medicine composition is prepared into tablets according to the conventional tablet preparation process.
  • the prescription is:
  • the preparation method of the traditional Chinese medicine composition is as follows: same as the preparation method described in Example 1
  • the obtained traditional Chinese medicine composition is prepared into a capsule according to the conventional capsule preparation process.
  • the prescription is:
  • the preparation method of the traditional Chinese medicine composition is as follows: same as the preparation method described in Example 1
  • the obtained traditional Chinese medicine composition is prepared into a capsule according to the conventional capsule preparation process.
  • the prescription is:
  • the preparation method is:
  • the obtained traditional Chinese medicine composition is prepared into a capsule according to the conventional capsule preparation process.
  • the prescription is:
  • Big belly skin 120g Cangzhu 30g Aloe 120g
  • the preparation method of the traditional Chinese medicine composition is as follows:
  • the obtained traditional Chinese medicine composition is prepared into a capsule according to the conventional capsule preparation process.
  • Example 7 Capsules: 0.378g/kg (high dose), 0.189g/kg (medium dose), 0.0945g/kg (low dose);
  • Example 8 Capsule: 0.378g/kg
  • Comparative Example 1 capsule 0.378g/kg
  • Bumetanide tablets 0.18mg/kg.
  • rat motilin MDL
  • gastrin GAS
  • vasoactive intestinal peptide VIP
  • Rats were injected intraperitoneally with hydrocortisone of 3.75mg/ml body weight daily.
  • adriamycin (0.9% sodium chloride) was injected into the tail vein at 1ml/100g body weight in the afternoon of the first day and the afternoon of the eighth day.
  • the solution was diluted to 0.4mg/ml) and injected at 4mg/kg on the 1st day and 3.5mg/kg on the 8th day for a total of 10 days.
  • each administration group was given corresponding dose of liquid medicine; blank control group and model group were given the same amount of distilled water.
  • the urine protein content is shown in Table 1. Compared with the blank group, the urine protein content of rats in the other groups increased significantly (P ⁇ 0.05, P ⁇ 0.01); compared with the model group, the urine protein content of rats in each administration group decreased significantly (P ⁇ 0.05, P ⁇ 0.01); Compared with the positive drugs, the rats in the high and medium dose groups of the present invention have a larger decline (P ⁇ 0.05, P ⁇ 0.01), there is no difference in the low dose group, and the comparative group has a smaller decline, and the difference is significant (P ⁇ 0.05, P ⁇ 0.01).
  • the cyclic nucleotide system is shown in Table 2. Compared with the blank group, the cAMP and cAMP/cGMP of the other groups decreased, and the cGMP increased (P ⁇ 0.05, P ⁇ 0.01); compared with the model group, each group was given In the drug group, cAMP and cAMP/cGMP were significantly increased, and cGMP was significantly decreased (P ⁇ 0.05, P ⁇ 0.01); compared with the positive drug, the rats in the high and medium dose groups of the present invention increased or decreased significantly (P ⁇ 0.05, P ⁇ 0.01), there was no difference in the low-dose group of rats, and the rats in the control group had a smaller increase or decrease, and the difference was significant (P ⁇ 0.05, P ⁇ 0.01).
  • Example 8 Capsules: 0.378g/kg (high dose), 0.189g/kg (medium dose), 0.0945g/kg (low dose);
  • Bumetanide tablets 0.18mg/kg.
  • rat motilin MDL
  • gastrin GAS
  • vasoactive intestinal peptide VIP
  • Rats were given thyroxine (15mg/ml) by intragastric administration according to 1ml/100g body weight every morning; in addition, 1ml/100g body weight was injected with adriamycin (0.9 % Sodium chloride solution was diluted to 0.4mg/ml) and injected at 4mg/kg on the first day and 3.5mg/kg body weight on the eighth day for a total of 10 days.
  • adriamycin 0.9 % Sodium chloride solution was diluted to 0.4mg/ml
  • each administration group was given corresponding dose of liquid medicine; blank control group and model group were given the same amount of distilled water.
  • the cyclic nucleotide system is shown in Table 5. Compared with the blank group, cAMP and cAMP/cGMP of rats in the other groups increased, and cGMP decreased (P ⁇ 0.05, P ⁇ 0.01); in the yin deficiency and edema group, compared with Compared with the model group, the cAMP and cAMP/cGMP of the rats in each administration group were significantly reduced, and the cGMP was significantly increased (P ⁇ 0.05, P ⁇ 0.01); compared with the positive drug, the high and medium dose rats of the present invention decreased or increased The range of high was larger (P ⁇ 0.05, P ⁇ 0.01), and there was no difference in the low-dose group. The range of decrease or increase in rats in the control group was small, and the difference was significant (P ⁇ 0.05, P ⁇ 0.01).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Medical Informatics (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Mycology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)

Abstract

一种中药组合物及其用途，所述中药组合物由枳实、白术、人参、枸杞子、阿胶、何首乌、决明子、芦荟制备而成。药理实验表明：该中药组合物对于大鼠水肿甲状腺水平、尿蛋白含量、环核苷酸系统、血清蛋白与血脂水平具有良好的调控作用，与模型组相比，具有显著性的差异，对于各种原因引起的水肿具有良好的治疗效果。

Description

一种用于制备治疗水肿药物的中药组合物 技术领域
本发明涉及一种中药组合物的新用途，具体涉及中药组合物在制备治疗水肿药物中的用途，属于中药技术领域。
 背景技术
水肿是指人体组织间隙有过多的液体积聚使组织肿胀。根据分布的范围，水肿可表现为局部性或全身性水肿。根据水肿的程度可以分为轻、中、重度水肿，轻度水肿仅见于眼睑、眶下软组织，胫骨前、踝部的皮下组织，指压后可见组织轻度凹陷，体重可增加5%左右。中度：全身疏松组织均可有可见性水肿，指压后可出现明显的或较深的组织凹陷，平复缓慢。重度：全身组织严重水肿，身体低垂皮肤紧张发亮，甚至可有液体渗出，有时可伴有胸腔、腹腔、鞘膜腔积液。
水肿的发生机制主要包括机体内外液体交换失衡和血管内外液体失衡。体内外液体交换失衡（钠水潴留）的主要原因是肾小球滤过功能与肾小管重吸收功能失衡，导致钠水潴留和细胞外液量增多，包括肾小球滤过率下降、肾血流重分布、近端小管重吸收钠水增多、远端小管和集合管重吸收钠水增多；机体组织液在有效滤过压作用下虽生成略大于回流，但可通过淋巴回流而维持血管内外液体的动态平衡，若这一动态平衡被破坏，则使得血管内外液体失衡，产生水肿，破坏这一动态平衡的主要原因有血浆胶体渗透压降低、毛细血管内流体静力压升高、毛细血管通透性增高、淋巴液回流受阻、肾素-血管紧张素-醛固酮系统辅助水钠潴留。
目前，水肿的治疗主要的采用对因治疗、对症治疗、限制水、钠的摄入，严密监控液体出入量等方式。水肿的药物治疗主要为西医药物疗法，治疗的药物主要为利尿剂、脱水药、血浆制品和白蛋白。利尿剂等药物虽然可以在短时间内排出体内过多的体液，但是利尿剂的长期应用常常会造成体内电解质、体液平衡失调，血压下降，代谢紊乱，糖耐量降低等不良反应的发生。
中医辩证，水肿是指因感受外邪、饮食失调或劳倦过度，使肺失通调、脾失传输、肾失气化、膀胱开合不利，导致体内水湿潴留，泛溢肌肤，表现以头面、眼帘、四肢、腹背甚至全身浮肿为主要临床表现的病证。水肿的形成与风邪袭表、外感水湿、饮食不节、体虚劳伤有关。水肿病位在肺、脾、肾，而关健在于肾。病因多为风邪、水湿、疮毒、瘀血。病机特点为肺失通调、脾失传输、肾失开合，水液潴留，泛滥成肿。病性总属本虚标实，有阴水、阳水之分，两者在一定的条件下可相互转化。
中医治疗水肿采用治疗与调理相结合的方式进行，具有改善症状明显、利水消肿和缓稳定、不良反应少等优点。采用中医药治疗水肿，不仅能够利水消肿，恢复脏器功能，还有利于控制疾病的发展，避免对脏器的损害，同时避免激素类药物治疗带来的不良反应。
对于水肿的治疗，与西药相比，中医药有着独特的优势，已成为一种有效而可行的治疗手段。
中国专利CN100453105C公开了一种具有通便排毒、减肥降脂功能的组合物及制备方法。该组合物是由何首乌、芦荟、决明子、枸杞子、阿胶、人参、白术、枳实八味中药组方，对毒邪内蕴、阴液亏虚所致的便秘具有良好的治疗作用。相关产品已经上市，产品名为“首荟通便胶囊”。
 技术问题
本发明是在中国发明专利CN100453105C的基础上开发的中药组合物在治疗水肿中的新用途。
 技术解决方案
本发明所述的中药组合物主要由枳实、白术、人参、枸杞子、阿胶、何首乌、决明子、芦荟制备而成。
上述中药组合物中各组分以重量份计为：
枳实50-200           白术20-100         芦荟30-600
枸杞子30-150         阿胶30-150           何首乌25-400 
决明子30-500         人参20-100。
优选的，所述中药组合物各组分以重量份计为：
枳实80-150           白术20-80         芦荟100-200
枸杞子30-100         阿胶30-100        何首乌60-150
决明子80-180         人参20-80；
优选的，所述中药组合物各组分以重量份计为：
枳实80-120            白术30-50         芦荟120-160
枸杞子50-80           阿胶40-80         何首乌80-120 
决明子100-150         人参20-50；
更优选地方案之一，上述中药组合物中各组分以重量份计为：
枳实110               白术50             芦荟130
枸杞子70              阿胶60            何首乌80 
决明子100            人参30；
更优选的方案之二，上述中药组合物中各组分以重量份计为：
枳实120             白术50            芦荟160
枸杞子75              阿胶75            何首乌120
决明子140           人参50。
水肿的发病的基本病理变化在于，肺失通调、脾失传输、肾失开合、三焦气化不利。《景岳全书•肿胀》篇指出：“凡水肿等证，乃肺脾肾三脏相干之病，盖水为至阴，故其本在肾；水化于气，故其标在肺；水唯畏土，故其制在脾。”
中医理论认为：
脾主运化，包括运化水谷和运化水液。脾具有吸收、输布水液，防止水液在体内停滞的作用。人体所摄入的水液需经过脾的吸收和转化以布散全身而发挥滋养、濡润的作用；同时，脾又把各组织器官利用后的多余水液，及时地转输给肺和肾，通过肺和肾的气化，化为汗和尿排出体外。脾主运化水液的功能强健，既能是全身各组织器官得到水液的充分滋养，又能防止水液在体内发生不正常的停留，从而维持人体水液代谢的相对平衡。反之，如果脾运化水液的功能市场，水液不能布散而停滞体内，就可产生水肿。本发明中药组合物中，以枳实、白术为君药，二者同归脾经，可燥湿利水、健脾益气。二者合用，共取其燥湿健脾，利尿消肿之功效，快速排出体内滞留的水液。
水液的正常代谢，与五脏系统功能正常，阴阳平衡密切相关，阴阳并需，尤以阳气为要，阳旺则气化，气化则水自化。肾司开合，为主水之脏。脾主运化水液，为水液代谢之枢纽。肺主行水，为水之上源。肝主疏泄，调畅气机，气行则水行。心主血脉，行血而利水运。饮水入胃，中焦之水经脾气的运化，肝气的疏泄，散精于上焦；心肺同居上焦，上焦之水为清水，清中之清者经肺气宣发，心脉通利而散布到肌腠、皮毛、四肢、百骸，其代谢废物即变为汗液等排出体外；清中之浊者得肺气肃降而输达下焦；归肾之水为浊，浊中之清者复经肾气的蒸腾上升至心肺而重新参加代谢，浊中之浊者经肾气开合送至膀胱，而排出体外。若在水代谢过程中某一脏器出现问题，必使水液滞留于体内，形成水肿、浮肿。故方中以何首乌、人参、阿胶为臣药，人参归脾、肺、心、肾经，何首乌归肝、心、肾经，阿胶归肺、肝、肾经，三者合用，通调五脏与三焦，使水道通畅，维持体内水液平衡。此外，以决明子、芦荟为佐药，二者同归肝、大肠经，肝主疏泄，调畅气机，气行则水行，助推水液在体内的代谢；大肠在排出糟粕之时，可带走残留水分，为津液排泄的一条途径，可消除水肿。
人体水液代谢的全过程，需要五脏六腑生理功能的协同配合，又是以肺、脾、肾三脏的功能活动为主。水肿的发病的基本病理变化在于，肺失通调、脾失传输、肾失开合、三焦气化不利。《景岳全书•肿胀》篇指出：“凡水肿等证，乃肺脾肾三脏相干之病，盖水为至阴，故其本在肾；水化于气，故其标在肺；水唯畏土，故其制在脾。”水肿之证，其本在肾，方中以枸杞子为使药，归肾经，引领诸药直达肾经，促进人体内水液代谢。
上述中药组方中，临床上治疗各种原因引起的水肿具有显著地疗效。
特别的，本发明所述水肿包括全身性水肿、局部性水肿。
优选的，上述全身性水肿包括心源性水肿、肾源性水肿、肝源性水肿、营养不良型水肿、药物性水肿。
优选的，上述局部性水肿是指由于局部静脉、淋巴回流受阻或毛细血管通透性增加所引起的水肿。
本发明还提供了上述中药组合物的制备方法，其制备步骤如下：
（1）取阿胶磨成细粉过80目筛，备用；
（2）取人参、何首乌、决明子、芦荟，60%乙醇回流提取2次，合并提取液，过滤，滤液Ⅰ备用；
（3）取处方量枸杞子、白术、枳实，加水煎煮两次，合并煎煮液，过滤并浓缩至相对密度为1.10-1.20（80℃）的清膏，放至室温，加乙醇使其含醇量为60%，静置24小时，滤过，滤液Ⅱ备用；
（4）将步骤（2）所得滤液Ⅰ与步骤（3）所得滤液Ⅱ合并，浓缩至相对密度为1.30-1.35（70℃）的稠膏，干燥，粉碎，加入步骤（1）制备的阿胶细粉，即得中药组合物。
上述步骤所制备的中药组合物经过常规工序直接或加入药学上可接受的赋形剂制备成临床可接受的剂型，如口服药物制剂。
优选地，所述口服药物制剂为丸剂、颗粒剂、胶囊剂、片剂、口服液或糖浆剂等临床上常规的口服剂型。
进一步优选地，所述口服药物制剂为胶囊剂。
 有益效果
与现有技术相比，本发明取得了显著的技术效果：
动物药理学试验表明，本发明中药组合物可有效治疗或消除大鼠水肿，修复肾组织、减轻肾损伤。动物实验表明，经本发明中药组合物治疗后的肾阴虚水肿大鼠T4、cAMP、cAMP/cGMP、Cre、BUN显著降低，cGMP显著升高，表明大鼠甲状腺轴功能得以较好的恢复，阴虚症状得以很好的治疗，肾功能得以恢复。阳虚水肿大鼠经本发明中药组合物治疗后cGMP、Cre、BUN显著降低、T4、cAMP、cAMP/cGMP显著升高，表明大鼠甲状腺轴功能得以较好的恢复，阳虚症状减轻，肾功能恢复，阳虚状态得以缓解，尿蛋白含量显著降低，水肿状态得以缓解。
 本发明的实施方式
下述实施例为进一步公开本发明，需要说明的是这些实施例仅为本发明的优选方案，并不限制本发明要求保护的范围。
实施例1  
处方为：
枳实200g       白术20g芦荟30g
枸杞子30g     阿胶150g         何首乌25g 
决明子500g     人参100g。
制备方法：
（1）取阿胶磨成细粉过80目筛，备用；
（2）取人参、何首乌、决明子、芦荟，60%乙醇回流提取2次，合并提取液，过滤，滤液Ⅰ备用；
（3）取处方量枸杞子、白术、枳实，加水煎煮两次，合并煎煮液，过滤并浓缩至相对密度为1.10-1.20（80℃）的清膏，放至室温，加乙醇使其含醇量为60%，静置24小时，滤过，滤液Ⅱ备用；
（4）将步骤（2）所得滤液Ⅰ与步骤（3）所得滤液Ⅱ合并，浓缩至相对密度为1.30-1.35（70℃）的稠膏，干燥，粉碎，，加入步骤（1）制备的阿胶细粉，即得中药组合物。所得中药组合物经过常规丸剂工艺制备成丸剂。
实施例2
处方为：
枳实50g       白术100g芦荟600g
枸杞子150g     阿胶30g         何首乌400g   
决明子30g     人参20g。
制备方法如下：同实施例1所述制备方法。
所得中药组合物按照常规糖浆剂制备工艺，制备成糖浆剂。
实施例3
处方为：
枳实150g       白术20g芦荟200g
枸杞子100g     阿胶30g         何首乌150g
决明子80g     人参20g。
中药组合物制备方法：同实施例1所述制备方法。
所得中药组合物按照常规颗粒剂制备工艺，制备成颗粒剂。
实施例4
处方为：
枳实80g       白术80g芦荟100g
枸杞子30g     阿胶100g         何首乌60g
决明子180g     人参80g。
中药组合物制备方法：同实施例1所述制备方法。
所得中药组合物按照常规口服液制备工艺，制备成口服液。
实施例5
处方为：
枳实80g       白术50g芦荟160g
枸杞子80g     阿胶40g         何首乌120g
决明子100g     人参20g。
中药组合物制备方法：同实施例1所述制备方法。
所得中药组合物按照常规胶囊剂制备工艺，制备成胶囊剂。
实施例6
处方为：
枳实120g       白术30g芦荟120g
枸杞子50g     阿胶80g         何首乌80g
决明子150g     人参50g。
中药组合物制备方法：同实施例1所述制备方法。
所得中药组合物按照常规片剂制备工艺，制备成片剂。
实施例7
处方为：
枳实110g        白术50g芦荟130g
枸杞子70g       阿胶60g何首乌80g
决明子100g        人参30g
中药组合物制备方法如下：同实施例1所述制备方法
所得中药组合物按照常规胶囊剂制备工艺，制备成胶囊剂。
实施例8
处方为：
枳实120g           白术50 g            芦荟160 g
枸杞子75 g              阿胶75 g           何首乌120 g
决明子140 g          人参50 g
中药组合物制备方法如下：同实施例1所述制备方法
所得中药组合物按照常规胶囊剂制备工艺，制备成胶囊剂。
 
对比实施例1
处方为：
枳实120g       白术30g大黄120g
枸杞子50g阿胶80g          何首乌80g 
郁李仁150g     人参50g。
制备方法为：
（1）取阿胶磨成细粉过80目筛，备用；
（2）取人参、何首乌、郁李仁、大黄，60%乙醇回流提取2次，合并提取液，过滤，滤液Ⅰ备用；
（3）取处方量枸杞子、白术、枳实，加水煎煮两次，合并煎煮液，过滤并浓缩至相对密度为1.10-1.20（80℃）的清膏，放至室温，加乙醇使其含醇量为60%，静置24小时，滤过，滤液Ⅱ备用；
（4）将步骤（2）所得滤液Ⅰ与步骤（3）所得滤液Ⅱ合并，浓缩至相对密度为1.30-1.35（70℃）的稠膏，干燥，粉碎，，加入步骤（1）制备的阿胶细粉，即得中药组合物。
所得中药组合物按照常规胶囊剂制备工艺，制备成胶囊剂。
对比实施例2
处方为：
大腹皮120g       苍术30g芦荟120g
枸杞子50g       阿胶80g          何首乌80g 
决明子150g     人参50g。
中药组合物制备方法如下：
（1）取阿胶磨成细粉过80目筛，备用；
（2）取人参、何首乌、决明子、芦荟，60%乙醇回流提取2次，合并提取液，过滤，滤液Ⅰ备用；
（3）取处方量枸杞子、苍术、大腹皮，加水煎煮两次，合并煎煮液，过滤并浓缩至相对密度为1.10-1.20（80℃）的清膏，放至室温，加乙醇使其含醇量为60%，静置24小时，滤过，滤液Ⅱ备用；
（4）将步骤（2）所得滤液Ⅰ与步骤（3）所得滤液Ⅱ合并，浓缩至相对密度为1.30-1.35（70℃）的稠膏，干燥，粉碎，，加入步骤（1）制备的阿胶细粉，即得中药组合物。
所得中药组合物按照常规胶囊剂制备工艺，制备成胶囊剂。
 工业实用性
为验证本发明中药组合物治疗水肿的功效，发明人开展了试验研究，以下以肾源性（阴虚、阳虚）水肿为例进行说明，但是发明人要说明的是，本发明人对说明书中描述的其他原因引起的水肿亦进行了药理实验研究，本发明组合物亦可以达到相同或类似的效果，在此不再一一叙述。
（一）、 本发明中药组合物对肾源性（阳虚）水肿模型大鼠的治疗作用。
1材料
1.1动物：
雄性SD级大鼠，体重180～220g，实验动物许可证号：SCXK(鲁) 2014 0007，由济南朋悦实验动物繁育有限公司提供，实验前适应性饲养一周。
1.2 药物、试剂
1.2.1 药物
本发明实施例7、8所得胶囊剂
对比例对比实施例1所得胶囊剂
阳性药布美他尼片
1.2.3 大鼠用药剂量
实施例7胶囊剂：0.378g/kg（高剂量）、0.189g/kg（中剂量）、0.0945g/kg（低剂量）；
实施例8胶囊剂：0.378g/kg；
对比实施例1胶囊剂：0.378g/kg；
布美他尼片：0.18mg/kg。
按照10ml/kg灌服。
1.2.4 试剂：大鼠胃动素（MTL）、胃泌素（GAS）、血管活性肠肽（VIP）试剂盒。
2. 试验方法
2.2.1 造模方法
大鼠每日腹腔注射3.75mg/ml体质量的氢化可的松，此外，于造模第1天下午、第8天下午按照1ml/100g体质量尾静脉注射阿霉素（0.9%氯化钠溶液稀释成0.4mg/ml），第1天按照4mg/kg、第8天按照3.5mg/kg体质量注射，共计造模10天。
2.2.2 分组
取阳虚水肿造模成功的大鼠70只，随机分为7组，每组10只，分别为模型组、阳性药组、对比例组、实施例7三个剂量组、实施例8组；
另取正常大鼠10只，为空白组。
2.2.3 给药造模结束第2天，各给药组分别灌以相应剂量的药液；空白对照组及模型组给予等量的蒸馏水。
每日给药1次，时间固定，持续时间2周。
2.2.4 检测
最后一次灌药24小时后，腹动脉取血，室温放置2h，低温离心，取血清。
检测Cre、BUN、TG、TC、ALB、TP和尿蛋白；cAMP、cGMP；T3、T4。
3. 结果及结论
3.1 实验结果
Figure 453898dest_path_image001
注：与空白组对比， @P＜0.05， *P＜0.01；
与模型组对比， △P＜0.05， #P＜0.01；
与阳性药组对比， &P＜0.05， ￥P＜0.01。
Figure 587552dest_path_image002
注：与空白组对比， @P＜0.05， *P＜0.01；
与模型组对比， △P＜0.05， #P＜0.01；
与阳性药组对比， &P＜0.05， ￥P＜0.01。
Figure 256430dest_path_image003
注：与空白组对比， @P＜0.05， *P＜0.01；
与模型组对比， △P＜0.05， #P＜0.01；
与阳性药组对比， &P＜0.05， ￥P＜0.01。
3.2 实验结论
3.2.1  甲状腺水平见表1。与空白组相比，其余各组大鼠T3、T4显著降低（P＜0.05，P＜0.01）；与模型组相比，各给药组大鼠T3、T4显著升高（P＜0.05，P＜0.01）；与阳性药组相比，本发明高、中剂量大鼠升高幅度较大（P＜0.05，P＜0.01），低剂量组无差别，对比例组升高幅度较小，差异显著（P＜0.05，P＜0.01）。
3.2.2 尿蛋白含量见表1。与空白组相比，其余各组大鼠尿蛋白含量均显著增加（P＜0.05，P＜0.01）；与模型组对比，各给药组大鼠尿蛋白含量均显著下降（P＜0.05，P＜0.01）；与阳性药对比，本发明高、中剂量组大鼠下降的幅度较大（P＜0.05，P＜0.01），低剂量组无差异，对比例组下降的幅度较小，差异显著（P＜0.05，P＜0.01）。
3.2.3  肾功能指标见表2。与空白组相比，其余各组大鼠Cre、BUN含量均显著升高（P＜0.05，P＜0.01）；与模型组相比，各给药组大鼠Cre、BUN含量显著降低（P＜0.05，P＜0.01）；与阳性药组相比，本发明高、中剂量组大鼠降低幅度较大（P＜0.05，P＜0.01），低剂量组无差别，对比例组降低幅度较小，差异显著（P＜0.05，P＜0.01）。
3.2.4  环核苷酸系统见表2.与空白组相比，其余各组大鼠cAMP和cAMP/cGMP降低，cGMP升高（P＜0.05，P＜0.01）；与模型组对比，各给药组大鼠cAMP和cAMP/cGMP显著升高，cGMP显著降低（P＜0.05，P＜0.01）；与阳性药对比，本发明高、中剂量组大鼠升高或降低的幅度较大（P＜0.05，P＜0.01），低剂量组大鼠无差别，对比例组大鼠升高或降低的幅度较小，差异显著（P＜0.05，P＜0.01）。
3.2.5 血清蛋白与血脂水平见表3。与空白组相比，其余各组大鼠TP、ALB降低，TG、TC升高（P＜0.05，P＜0.01）；与模型组相比，各给药组TP、ALB显著升高，TG、TC显著降低（P＜0.05，P＜0.01）；与阳性药组相比，本发明高、中剂量组大鼠升高或降低的幅度较大（P＜0.05，P＜0.01），低剂量组大鼠无差别，对比例组大鼠升高或降低的幅度较小，差异显著（P＜0.05，P＜0.01）。
 
（二）、 本发明中药组合物对肾源性（阴虚）水肿模型大鼠的治疗作用。
1材料
1.1动物：
雄性SD级大鼠，体重180～220g，实验动物许可证号：SCXK(鲁) 2014 0007，由济南朋悦实验动物繁育有限公司提供，实验前适应性饲养一周。
1.2 药物、试剂
1.2.1 药物
本发明实施例8所得胶囊剂
对比例对比实施例2所得胶囊剂
阳性药布美他尼片
1.2.3 大鼠用药剂量
实施例8胶囊剂：0.378g /kg（高剂量）、0.189g/kg（中剂量）、0.0945g/kg（低剂量）；
对比实施例2胶囊剂：0.378g/kg；
布美他尼片：0.18mg/kg。
按照10ml/kg灌服。
1.2.4 试剂：大鼠胃动素（MTL）、胃泌素（GAS）、血管活性肠肽（VIP）试剂盒。
2. 试验方法
2.2.1 造模方法
大鼠每日上午按照1ml/100g体质量灌胃给予甲状腺素（15mg/ml）；此外，于造模第1天下午、第8天下午按照1ml/100g体质量尾静脉注射阿霉素（0.9%氯化钠溶液稀释成0.4mg/ml），第1天按照4mg/kg、第8天按照3.5mg/kg体质量注射，共计造模10天。
2.2.2 分组及给药取阴虚水肿造模成功的大鼠60只，各随机分为6组，每组10只，分别为模型组、阳性药组、对比例组、本发明三个剂量组；
另取正常大鼠10只，为空白组。
2.2.3 给药造模结束第2天，各给药组分别灌以相应剂量的药液；空白对照组及模型组给予等量的蒸馏水。
每日给药1次，时间固定，持续时间2周。
2.2.4 检测
最后一次灌药24小时后，腹动脉取血，室温放置2h，低温离心，取血清。
检测Cre、BUN、TG、TC、ALB、TP和尿蛋白；cAMP、cGMP；T3、T4。
3. 结果及结论
3.1 实验结果
Figure 187477dest_path_image004
注：与空白组对比， @P＜0.05， *P＜0.01；
与模型组对比， △P＜0.05， #P＜0.01；
与阳性药组对比， &P＜0.05， ￥P＜0.01。
Figure 941807dest_path_image005
注：与空白组对比， @P＜0.05， *P＜0.01；
与模型组对比， △P＜0.05， #P＜0.01；
与阳性药组对比， &P＜0.05， ￥P＜0.01。
Figure 678818dest_path_image006
注：与空白组对比， @P＜0.05， *P＜0.01；
与模型组对比， △P＜0.05， #P＜0.01；
与阳性药组对比， &P＜0.05， ￥P＜0.01。
3.2 实验结论
3.2.1  甲状腺水平见表4。与空白组相比，其余各组大鼠T3、T4显著升高（P＜0.05，P＜0.01）；与模型组相比，各给药组大鼠T3、T4显著降低（P＜0.05，P＜0.01）；与阳性药相比，本发明高、中剂量大鼠降低的幅度较大（P＜0.05，P＜0.01），低剂量组无差别，对比例组大鼠降低的幅度较小，差异显著（P＜0.05，P＜0.01）。
3.2.2 尿蛋白含量见表4。与空白组相比，其余各组大鼠的尿蛋白含量均显著增加（P＜0.05，P＜0.01）；与模型组对比，各给药组大鼠尿蛋白含量均显著下降（P＜0.05，P＜0.01）；与阳性药相比，本发明高、中剂量大鼠降低的幅度较大（P＜0.05，P＜0.01），低剂量组无差别，对比例组大鼠下降的幅度较小，差异显著（P＜0.05，P＜0.01）。
3.2.3  肾功能指标见表5。与空白组相比，其余各组大鼠Cre、BUN含量均显著升高（P＜0.05，P＜0.01）；与模型组相比，各给药组大鼠Cre、BUN含量显著降低（P＜0.05，P＜0.01）；与阳性药相比，本发明高、中剂量大鼠降低的幅度较大（P＜0.05，P＜0.01），低剂量组无差别，对比例组大鼠的降低幅度较小，差异显著（P＜0.05，P＜0.01）。
3.2.4  环核苷酸系统见表5.与空白组相比，其余各组大鼠cAMP和cAMP/cGMP升高，cGMP降低（P＜0.05，P＜0.01）；阴虚水肿组中，与模型组相比，各给药组大鼠cAMP和cAMP/cGMP显著降低，cGMP显著升高（P＜0.05，P＜0.01）；与阳性药相比，本发明高、中剂量大鼠降低或升高的幅度较大（P＜0.05，P＜0.01），低剂量组无差别，对比例组大鼠降低或升高的幅度较小，差异显著（P＜0.05，P＜0.01）。
3.2.5 血清蛋白与血脂水平见表6。与空白组相比，阴虚水肿组TP、ALB降低，TG、TC升高（P＜0.05，P＜0.01）；与模型组相比，各给药组TP、ALB显著升高，TG、TC显著降低（P＜0.05，P＜0.01）；与阳性药相比，本发明高、中剂量大鼠降低或升高的幅度较大（P＜0.05，P＜0.01），低剂量组无差别，对比例组大鼠升高或降低的幅度较小，差异显著（P＜0.05，P＜0.01）。

Claims (10)

  1. 一种主要由枳实、白术、芦荟、枸杞子、阿胶、何首乌、决明子、人参制备而成中药组合物在制备治疗水肿药物中的用途。
  2. 如权利要求1所述的用途，其特征在于，所述水肿包括全身性水肿、局部性水肿。
  3. 如权利要求2所述的用途，其特征在于，所述全身性水肿包括心源性水肿、肾源性水肿、肝源性水肿、营养不良型水肿、药物性水肿。
  4. 如权利要求2所述的用途，其特征在于，所述局部性水肿是指由于局部静脉、淋巴回流受阻或毛细血管通透性增加所引起的水肿。
  5. 如权利要求1所述的用途，其特征在于，所述中药组合物各组分以重量份计为：
    枳实50-200           白术20-100         芦荟30-600
    枸杞子30-150         阿胶30-150           何首乌25-400 
    决明子30-500         人参20-100。
  6. 如权利要求5所述的用途，其特征在于，所述中药组合物各组分以重量份计为：
    枳实80-150           白术20-80         芦荟100-200
    枸杞子30-100         阿胶30-100        何首乌60-150
    决明子80-180         人参20-80。
  7. 如权利要求6所述的用途，其特征在于，所述中药组合物各组分以重量份计为：
    枳实80-120            白术30-50         芦荟120-160
    枸杞子50-80           阿胶40-80         何首乌80-120 
    决明子100-150         人参20-50。
  8. 如权利要求7所述的用途，其特征在于，所述中药组合物各组分以重量份计为：
    枳实110               白术50             芦荟130
    枸杞子70              阿胶60            何首乌80 
    决明子100            人参30。
  9. 如权利要求1-8任一项所述的用途，其特征在于，所述中药组合物经过常规工序直接或加入药学上可接受的赋形剂制备成临床可接受的剂型。
  10. 如权利要求9所述的用途，其特征在于，所述临床可接受的剂型为口服药物制剂，优选地，所述口服制剂为丸剂、颗粒剂、胶囊剂、片剂、口服液或糖浆剂；进一步优选地，所述口服制剂为胶囊剂。
PCT/CN2019/106121 2019-09-17 2019-09-17 一种用于制备治疗水肿药物的中药组合物 WO2021051262A1 (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/CN2019/106121 WO2021051262A1 (zh) 2019-09-17 2019-09-17 一种用于制备治疗水肿药物的中药组合物
CN201980031448.0A CN114450021B (zh) 2019-09-17 2019-09-17 一种用于制备治疗水肿药物的中药组合物

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2019/106121 WO2021051262A1 (zh) 2019-09-17 2019-09-17 一种用于制备治疗水肿药物的中药组合物

Publications (1)

Publication Number Publication Date
WO2021051262A1 true WO2021051262A1 (zh) 2021-03-25

Family

ID=74883296

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/106121 WO2021051262A1 (zh) 2019-09-17 2019-09-17 一种用于制备治疗水肿药物的中药组合物

Country Status (2)

Country Link
CN (1) CN114450021B (zh)
WO (1) WO2021051262A1 (zh)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040223962A1 (en) * 2003-05-07 2004-11-11 Riordan Neil H. Method and composition for preventing or reducing edema, deep vein thrombosis and/or pulmonary embolism
CN100453105C (zh) * 2004-09-17 2009-01-21 鲁南制药集团股份有限公司 一种具有通便排毒、减肥降脂功能的组合物及制备方法
US20090130239A1 (en) * 2007-11-15 2009-05-21 Korea Institute Of Oriental Medicine Method for preventing or treating edema or dermatitis using glehnia littoralis fr. schmidt et miquel extract
CN106123496A (zh) * 2016-06-30 2016-11-16 鲁南制药集团股份有限公司 一种中药浸膏的干燥方法
CN109464570A (zh) * 2018-11-23 2019-03-15 鲁南制药集团股份有限公司 一种首荟通便胶囊制备工艺

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106176909A (zh) * 2016-07-16 2016-12-07 江南大学 一种用人参白术茯苓甘草制备四君子酵素饮料的方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040223962A1 (en) * 2003-05-07 2004-11-11 Riordan Neil H. Method and composition for preventing or reducing edema, deep vein thrombosis and/or pulmonary embolism
CN100453105C (zh) * 2004-09-17 2009-01-21 鲁南制药集团股份有限公司 一种具有通便排毒、减肥降脂功能的组合物及制备方法
US20090130239A1 (en) * 2007-11-15 2009-05-21 Korea Institute Of Oriental Medicine Method for preventing or treating edema or dermatitis using glehnia littoralis fr. schmidt et miquel extract
CN106123496A (zh) * 2016-06-30 2016-11-16 鲁南制药集团股份有限公司 一种中药浸膏的干燥方法
CN109464570A (zh) * 2018-11-23 2019-03-15 鲁南制药集团股份有限公司 一种首荟通便胶囊制备工艺

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BINGBING LI, YAO TAN YUJUN, CHENG JINGCHUN, HUANG GUOLIANG, ZHANG GUIMIN ZHIYAN: "Effects of Shouhui Tongbian Capsule on Intestine Pushing Ｒate and Colonic Mucus Secretion in Ｒats with Slow Transit Constipation", WORLD CHINESE MEDICINE, vol. 13, no. 9, 1 September 2018 (2018-09-01), pages 2268 - 2271, XP055793242 *

Also Published As

Publication number Publication date
CN114450021B (zh) 2024-01-26
CN114450021A (zh) 2022-05-06

Similar Documents

Publication Publication Date Title
CN103272169B (zh) 一种红景天复方组合物在治疗糜烂性胃炎中的用途
CN103356956B (zh) 治疗自身免疫性肝病的中药组合物及其制备方法
CN102228603B (zh) 一种治疗尿潴留的中药
CN1742903B (zh) 治疗前列腺炎、前列腺增生的药物及其制备方法
CN1814215A (zh) 一种治疗痛风及痛风性关节炎的药物
CN103638136A (zh) 虫草芪参胶囊
CN103272170A (zh) 一种红景天复方组合物在制备治疗十二指肠溃疡的药物中的用途
CN115770279B (zh) 用于治疗慢性下肢静脉疾病的中药组合物及其汤剂和制剂
CN110856741A (zh) 一种中药组合物在制备治疗腹泻药物中的应用
CN102327395B (zh) 一种治疗产后恶露不尽的药物组合物及其制备方法
WO2021051262A1 (zh) 一种用于制备治疗水肿药物的中药组合物
CN111529645B (zh) 一种治疗肾虚络瘀型糖尿病肾病ⅳ期的药物
CN107669910B (zh) 治疗动脉粥样硬化的药物组合物
CN105902897A (zh) 一种治疗胰腺癌的药物制剂及其用途
CN101584805A (zh) 治疗心力衰竭的中药制剂
CN104225016A (zh) 一种治疗脾胃虚弱型慢性萎缩性胃炎的药物组合物
CN112206298A (zh) 一种中药组合物在制备治疗腹泻药物中的应用
CN104721595B (zh) 一种治疗高脂血症的中药组合物
CN113679757B (zh) 一种改善膀胱收缩力的药物组合物及其应用
CN110859945B (zh) 一种防治强直性脊柱炎的胶囊剂及其制备方法
CN102233004B (zh) 一种治疗肝病的药物
CN107213443B (zh) 一种治疗肾积水的中药组合物及雷火灸结合应用
CN100566746C (zh) 一种治疗前列腺疾病的中药复方及其制备方法和应用
CN106166206A (zh) 一种妇科炎症导致尿频的康复药物制备方法
CN105998519A (zh) 一种用于盆腔炎后遗尿频的口服药物

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 201980031448.0

Country of ref document: CN

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

Ref document number: 19945846

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: 19945846

Country of ref document: EP

Kind code of ref document: A1