CN104523727A - Medicine composition for treating diabetes - Google Patents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
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- 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
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
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- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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Abstract
The invention relates to a medicine composition for treating diabetes. The medicine composition comprises oroxin A, cucurbitacine E, hemiphroside B and clerodendrin A in proportion; and various dosage forms can be manufactured according to a conventional preparation technology. The medicine composition overcomes the defects in the prior art; and the medicine composition for treating the diabetes is provided.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of pharmaceutical composition for the treatment of diabetes.
Background technology
Along with the aging of world population, diabetes have become a kind of commonly encountered diseases, frequently-occurring disease, and in industrially developed country, its sickness rate is in rising trend.According to statistics, about there are 1.5 hundred million diabeticss in the whole world, and 80% is non-insulin-dependent diabetes mellitus (2 type), and wherein China about has 3,000 ten thousand.The death toll caused by diabetic complication has been the rank rear the 3rd of cardiovascular and cerebrovascular disease, cancer of continuing in developed country, causes the great attention of countries in the world, studies one after another to the pathogenesis, medical treatment etc. of diabetes.Because the type 1 diabetes cause of disease is substantially clear and definite, only need supplementation with insulin, type 2 diabetes mellitus is then more complicated, and what current China medical circle was taked it is the complex treatment measure comprising dietetic therapy, Drug therapy and other complementary therapy.Although Western medicine emerges in an endless stream, can not tackle the problem at its root, and western medicine has certain side effect and " failure in treatment ".TCM Treatment of Diabetes is with a long history, and clinical experience enriches, evident in efficacy, has become recent domestic study hotspot.The understanding of Chinese medicine to diabetes is different from doctor trained in Western medicine, and the traditional Chinese medical science emphasizes Overall View, with the essence of the change of both yin, yangs reflection disease.Normal body is " YIN and YANG in a relative equilibrium ", equilibrium between yin and yang, and namely organismic internal environment maintains stable state, and carbohydrate metabolism also remains stable; And the toxic and side effects of Chinese medicine is relatively little, patient can long-term taking, and this is the advantage of the uniqueness that Western medicine can not be compared.
The traditional Chinese medical science thinks that diabetes to be burnt cloudy losing by lung, stomach, the dirty heat of kidney three, water paddy transfer not normal caused by.Its base
This pathogenesis is cloudy body fluid deficiency consumption, scorching inclined Sheng, and deficiency of kidney-YIN is originally, and lung dryness of the stomach heat is mark, sick then cloudy damage QI consumed sun wound of a specified duration, and causes impairment of both QI and YIN, deficiency in both YIN and YANG, venation block, and the mistake of muscle arteries and veins is supported, and internal organs are impaired, gradually causes a series of double disease of appearance.
The course of disease of diabetes is processes of deficiency of YIN affecting YANG.Dialectical with the moon, from gently to heavy, be then the conversion of the deficiency of YIN-deficiency of both QI and YIN-deficiency of both YIN and YANG.And venation block is through the overall process of primary disease and double disease.
In recent years, some scholars have inquired into the relation of TCM Syndrome Differentiation of Diabetes and clinical biochemistry indications.From changes such as islet function, blood lipid level, sexual hormones, corticoid level, immunologic function machine hemorheologys, the dependency that observation diabetes typing and above index change, find the ANOMALOUS VARIATIONS of various index, from gently to heavy, how with the deficiency of YIN-deficiency of both QI and YIN-deficiency of both YIN and YANG future development.Embody the material base that diabetes typing is inquired in the combination of Chinese and Western medicine.
Determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs is the marrow of theory of Chinese medical science.The traditional Chinese medical science, according to the main pathogenesis of diabetes, distinguishes specimen weight that the is scorching and deficiency of YIN, payes attention to yin nourishing during medication, has scorching person then must heat clearing away, and yang blood and qi all loses, then yang blood and qi mending.According to modern pharmacology concept, mainly as follows to Chinese medicine diabetes Effect study.Single medicinal material: Rhizoma Coptidis and berberine, Fructus Momordicae charantiae, Radix Ginseng, the Radix Astragali, Radix Scutellariae, Folium Mori, herbal polysaccharide (as tremella polysaccharide, tremella polysaccharide spore, Auricularia polysaccharide, Hericium erinaceus polysaccharide, Porphyra Polysaccharide, Radix Ophiopogonis polysaccharide, laminaran (laminarin), lycium barbarum polysaccharide-X, lycium barbarum polysaccharide-D, Fructus Caricae polysaccharide and Cortex Moutan polysaccharide etc.), silymarin, Radix Et Rhizoma Rhei.In addition, oral administration of flavonoids puerarin (puerarin) or clausenacoumarine (clausenacoumarine) hyperglycemia to ALX animal also have reducing effect.The basic principle of TCM treatment of diabetes can be summarized as: nourishing YIN and clearing away heat, supplementing QI and nourishing YIN, kidney and spleen invigorating and blood circulation promoting and blood stasis dispelling etc.Conventional classic prescriptions has Ginseng Baihu Decoction, LIUWEI DIHUANG WAN, eight Dihuang Wans and a thousand pieces of gold coptis teeta pill etc., according to different pattern of syndrome and above-mentioned rule for the treatment of prescription or add and subtract with ancient prescription.
Oroxin A (oroxin A): CAS 57396-78-8, molecular formula C
21h
20o
10, molecular weight 432.38.
Cucurbatacin E (cucurbitacine E): CAS 18444-66-1, molecular formula C
32h
44o
8molecular weight 556.69.
Herba hemipharagmatis heterophylli glycosides B(Hemiphroside B), No. CAS: 165338-28-3, molecular formula C
31h
38o
17, molecular weight 682.6.
Clerodendrin A(clerodendrin A): No. CAS: 35481-70-0, molecular formula C
31h
42o
12, molecular weight 606.67.
4 kinds of medicines structures of pharmaceutical composition of the present invention are as follows:
Oroxin A (oroxin A) cucurbatacin E (cucurbitacine E)
Herba hemipharagmatis heterophylli glycosides B(Hemiphroside B) clerodendrin A(clerodendrin A).
Summary of the invention
The object of the invention is the deficiency overcoming background technology, a kind of pharmaceutical composition for the treatment of diabetes is provided.
The present invention is achieved through the following technical solutions:
Of the present invention a kind of treat the crude drug of the pharmaceutical composition of diabetes composition and weight portion be:
Oroxin A 5-25 weight portion cucurbatacin E 5-25 weight portion Herba hemipharagmatis heterophylli glycosides B5-25 weight portion clerodendrin A5-25 weight portion.
A kind of pharmaceutical composition for the treatment of diabetes of the present invention can adopt the conventional method of galenic pharmacy to be prepared into tablet, capsule, drop pill.
A kind of pharmaceutical composition for the treatment of diabetes of the present invention, is characterized in that being used for the treatment of diabetes.
Pharmaceutical composition provided by the invention, by blood sugar lowering, regulating blood lipid action research, result shows, has remarkable hypoglycemic activity to diabetic mice, can regulate diabetic mice blood lipid level simultaneously.Compare with model group, pharmaceutical composition of the present invention significantly can reduce alloxan and cause blood glucose in diabetic mice value (P<0.05), and significantly can reduce epinephrine and cause blood glucose in diabetic mice value (P<0.05).Administration group mice triacylglycerol, low density lipoprotein, LDL content significantly decline (P<0.05), and hdl concentration significantly raises (P<0.05).
Detailed description of the invention
Treat diabetes medicament composition and method of making the same below by specific experiment example and embodiment to one of the present invention to be described further, but be not limited to the present invention.
Embodiment 1: the pharmaceutical composition for the treatment of diabetes
Composition and the weight portion of the crude drug of the pharmaceutical composition for the treatment of diabetes are:
Oroxin A 5 weight portion cucurbatacin E 25 weight portion Herba hemipharagmatis heterophylli glycosides B5 weight portion clerodendrin A25 weight portion.
Embodiment 2: the pharmaceutical composition for the treatment of diabetes
Composition and the weight portion of the crude drug of the pharmaceutical composition for the treatment of diabetes are:
Oroxin A 25 weight portion cucurbatacin E 5 weight portion Herba hemipharagmatis heterophylli glycosides B25 weight portion clerodendrin A5 weight portion.
Embodiment 3: the pharmaceutical composition for the treatment of diabetes
Composition and the weight portion of the crude drug of the pharmaceutical composition for the treatment of diabetes are:
Oroxin A 15 weight portion cucurbatacin E 20 weight portion Herba hemipharagmatis heterophylli glycosides B10 weight portion clerodendrin A18 weight portion
Embodiment 4: the pharmaceutical composition for the treatment of diabetes
Composition and the weight portion of the crude drug of the pharmaceutical composition for the treatment of diabetes are:
Oroxin A 18 weight portion cucurbatacin E 15 weight portion Herba hemipharagmatis heterophylli glycosides B22 weight portion clerodendrin A16 weight portion.
Embodiment 5: the preparation of tablet
Example 1 compositions 150g, adds starch 75g, mixing, granulates, dry, adds microcrystalline Cellulose 20g, magnesium stearate 2.5g, and mixing, is pressed into 1000, obtains present composition tablet.
Embodiment 6: the preparation of capsule
Example 2 compositions 165g, adds starch 65g, mixing, granulates, and dry, granulate, adds appropriate magnesium stearate, and mixing, obtains present composition capsule by encapsulated 1000.
Embodiment 7: the preparation of drop pill
Taking polyethylene glycol 6000 200g water-bath (80 DEG C) heating boils molten, add embodiment 3 compositions 50g, stirring, is coolant with liquid paraffin, puts in glass tubing (4*80cm), chilling temperature is 10 DEG C, drip internal-and external diameter is 7.0/2.0 (mm/mm), and drip is 2cm apart from liquid level, drips speed with per minute 50 for optimum condition, blot the condensing agent on drop pill surface with cotton, obtain present composition drop pill.
Experimental example 1: pharmaceutical composition blood sugar lowering, regulating blood lipid action
1. medicine and reagent
The pharmaceutical composition that experimental drug thing is embodiment 1, embodiment 2 prepares, is numbered pharmaceutical composition 1, pharmaceutical composition 2(lot number: 20100822,20100823).Alloxan (Sigma Co., USA); Glucose kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number: 102401.201010); T-CHOL test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number: 101051.201007): triacylglycerol test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number: 104101.201008); High density lipoprotein test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number: 100361) low density lipoprotein, LDL test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number: 100271); Glibenclamide (Tianjin Lisheng Pharmaceutical Co., Ltd., lot number: 1003013); All the other agents useful for same are analytical pure.
2. laboratory animal
Kunming mouse, body weight l8-22 g, cleaning grade, male and female half and half, are provided by Mountain Western Medicine S University's Experimental Animal Center.It is consistent that this tests all animal feedings, starts to test front 3d and put the raising of this laboratory observation, freely ingest, drink water.Each group of feedstuff is originated all identical with drinking water.
3. instrument
Rotary evaporator RE-52AA (Shanghai Yarong Biochemical Instrument Plant); 752 ultraviolet-uisible spectrophotometers (Shanghai Precision Scientific Apparatus Co., Ltd); Centrifuge LXJ-IIB (Anting Scientific Instrument Factory, Shanghai); Electronic balance BS-124S (Beijing Sai Duolisi instrument system company limited)
4. experimental technique
4.1 cause the impact of blood glucose in diabetic mice and blood fat to alloxan
The freshly prepared alloxan 50mg/kg of mouse tail vein injection causes diabetes model, after 72 h.Fasting be can't help to the mouse orbit rear vein beard blood sampling of water, survey blood glucose value, choose the mice of fasting glucose higher than 11.1 mmol/L for experiment.Get qualified model mice 40, be divided into 4 groups at random, glibenclamide group (10), pharmaceutical composition 1, pharmaceutical composition 2 (often organizing each 10), diabetic model group, separately gets the normal mouse of similar weight as normal group (10).After successive administration 14 d. before last administration, water 8 h is can't help in mice fasting, continue fasting after administration and can't help 2 h after water, pluck eyeball and get blood, measure the fasting blood sugar of each group, total cholesterol level, triacylglycerol content, hdl concentration, low density lipoprotein, LDL content.
4.2 cause the impact of blood glucose in diabetic mice to epinephrine
Get qualified Kunming mouse 60 (male and female half and half), be divided into 4 groups at random, pharmaceutical composition 1, pharmaceutical composition 2 (often organizing 10) and glibenclamide group (10) dosage are with " 4.1 ", model group (10) and normal group (10) gavage equal-volume normal saline, successive administration 10 d.Before last administration, water 8 h is can't help in mice fasting, and continue after fasting can't help water 6 h after administration, except matched group, every mouse peritoneal Injection of Adrenaline 0.2 mg, Normal group is the capacity normal saline such as lumbar injection then.After 30 min, retroorbital venous clump is taken a blood sample, and measures the fasting blood sugar of each group.
4.3 statistical procedures
Experimental data mean ± standard deviation represents, makes t check the significance comparing group difference.
5. result
5.1 cause the impact of blood glucose in diabetic mice to alloxan
After successive administration 14 d, the mouse blood sugar value of pharmaceutical composition 1, pharmaceutical composition 2 all has significance to decline (P<0.05) compared with model group, with glibenclamide group mouse blood sugar value no significant difference (P>0.05), the results are shown in Table 1.
Table 1 pharmaceutical composition is on the impact of alloxan diabetes mouse blood sugar
Group | Dosage (g/kg) | Number of elements | Blood glucose (mmol/L) before administration | Administration 7d blood glucose value (mmol/L) | Administration 14d blood glucose value (mmol/L) |
Glibenclamide group | 0.002 | 10 | 23.34±4.97 | 13.67±2.22 * | 13.54±1.78 * |
Pharmaceutical composition 1 group | 0.006 | 10 | 22.98±4.36 | 13.57±1.96 * | 13.15±1.79 * |
Pharmaceutical composition 2 groups | 0.006 | 10 | 23.06±4.87 | 13.15±1.88 * | 13.09±1.65 * |
Model group | - | 10 | 23.13±4.54 # | 21.86±3.41 # | 20.97±3.01 # |
Normal group | - | 10 | 5.88±0. 36 | 5.93±0.39 | 6.10±0. 38 |
Note: compare with normal group,
#p<0.05; Compare with model group,
*p<0.05
5.2 cause the impact of blood glucose in diabetic mice to epinephrine
After administration 10d, lumbar injection adrenalin hydrochloride, model group mouse blood sugar value is significantly higher than normal group (P<0.05); Administration group mouse blood sugar value is all remarkable in model group (P<0.05), does not have significant difference (P>0.05) with glibenclamide group.The results are shown in Table 2.
Table 2 pharmaceutical composition is on the impact of epinephrine blood glucose in diabetic mice
Group | Dosage (g/kg) | Number of elements | Blood glucose value (mmol/L) |
Pharmaceutical composition 1 group | 0.006 | 10 | 6.79±1.28 * |
Pharmaceutical composition 2 groups | 0.006 | 10 | 7.25±1.11 * |
Glibenclamide group | 0.002 | 10 | 7.98±0.65 * |
Model group | - | 10 | 15.99±0.58 # |
Normal group | - | 10 | 5.24±0.56 |
Note: compare with Normal group,
#p<0.05; Compare with model control group,
*p<0.05
5.3 cause the impact of diabetic mice blood lipid level to alloxan
After administration 14 d. compare with normal group, diabetic groups mice TC, TG, LDL-C content significantly raises (P<0.05), and HDL-C content significantly declines (P<0.05); Compare with model group, administration group mice TG, LDL-C content significantly declines (P<0.05), and HDL-C content significantly raises (P<0.05).In table 3.
Table 3 pharmaceutical composition is on the impact of alloxan diabetes lipid of mice
Group | Dosage (g/kg) | TC(mmol/L) | TG(mmol/L) | HDL-C(mmol/L) | LDL-C(mmol/L) |
Pharmaceutical composition 1 group | 0.006 | 3.92±0.28 | 2.05±0.20 * | 1.27±0.15 * | 1.03±0.16 * |
Pharmaceutical composition 2 groups | 0.006 | 4.03±0.35 | 2.22±0.11 * | 1.36±0.10 * | 1.00±0.17 * |
Model group | - | 4.18±0.29 # | 4.58±0.14 # | 0.69±0.13 # | 1.35±0.42 # |
Normal group | - | 2.49±0.27 | 2.18±0.13 | 1.68±0.14 | 1.10±0.19 |
Note: compare with normal group,
#p<0.05; Compare with model group,
*p<0.05
Result shows: pharmaceutical composition of the present invention has remarkable hypoglycemic activity to diabetic mice, can regulate diabetic mice blood lipid level simultaneously.Compare with model group, pharmaceutical composition of the present invention significantly can reduce alloxan and cause blood glucose in diabetic mice value (P<0.05), and significantly can reduce epinephrine and cause blood glucose in diabetic mice value (P<0.05).Administration group mice triacylglycerol, low density lipoprotein, LDL content significantly decline (P<0.05), and hdl concentration significantly raises (P<0.05).
Claims (7)
1. treat a pharmaceutical composition for diabetes, it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Oroxin A 5-25 weight portion cucurbatacin E 5-25 weight portion Herba hemipharagmatis heterophylli glycosides B5-25 weight portion clerodendrin A5-25 weight portion.
2. according to claim 1: a kind of pharmaceutical composition for the treatment of diabetes, it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Oroxin A 5 weight portion cucurbatacin E 25 weight portion Herba hemipharagmatis heterophylli glycosides B5 weight portion clerodendrin A25 weight portion.
3. according to claim 1: a kind of pharmaceutical composition for the treatment of diabetes, it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Oroxin A 25 weight portion cucurbatacin E 5 weight portion Herba hemipharagmatis heterophylli glycosides B25 weight portion clerodendrin A5 weight portion.
4. according to claim 1: a kind of pharmaceutical composition for the treatment of diabetes, it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Oroxin A 15 weight portion cucurbatacin E 20 weight portion Herba hemipharagmatis heterophylli glycosides B10 weight portion clerodendrin A18 weight portion.
5. according to claim 1: a kind of pharmaceutical composition for the treatment of diabetes, it is characterized in that the composition of the crude drug making this pharmaceutical composition and weight portion are:
Oroxin A 18 weight portion cucurbatacin E 15 weight portion Herba hemipharagmatis heterophylli glycosides B22 weight portion clerodendrin A16 weight portion.
6. a kind of pharmaceutical composition for the treatment of diabetes according to claim 1, can adopt the conventional method of galenic pharmacy to be prepared into tablet, capsule, drop pill.
7. a kind of pharmaceutical composition for the treatment of diabetes according to claim 1, is characterized in that being used for the treatment of diabetes.
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CN104873528A (en) * | 2015-06-05 | 2015-09-02 | 泰山医学院 | Medicine composition for treating diabetes |
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CN101647801A (en) * | 2009-08-11 | 2010-02-17 | 华东师范大学 | Application of tetracyclic triterpenoids compound in preparing anti-angiogenic drugs |
CN101829243A (en) * | 2010-05-22 | 2010-09-15 | 祝根华 | External quick-acting cream for psoriasis and acne and production process |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN104873528A (en) * | 2015-06-05 | 2015-09-02 | 泰山医学院 | Medicine composition for treating diabetes |
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