CN100496561C - Medicine for improving sugar tolerance and treating diabetes and its preparation process - Google Patents
Medicine for improving sugar tolerance and treating diabetes and its preparation process Download PDFInfo
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- CN100496561C CN100496561C CNB031366538A CN03136653A CN100496561C CN 100496561 C CN100496561 C CN 100496561C CN B031366538 A CNB031366538 A CN B031366538A CN 03136653 A CN03136653 A CN 03136653A CN 100496561 C CN100496561 C CN 100496561C
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Abstract
The present invention discloses one kind of medicine for improving sugar tolerance, treating diabetes and obesity. The medicine includes at least two of cassia seed extractive, guava immature extractive Chinese lantern plant extractive. The present invention applies chemical genome theory and method to extract the active components with alpha-amylase inhibiting activity and fatty acid synthetase inhibiting activity from traditional Chinese medicinal materials. Animal experiment proves the obvious slimming effect, blood sugar reducing effect and no side effect. The present invention has important theoretical and practical significance in developing slimming medicine.
Description
Technical field
The present invention relates to a kind of medicine and preparation method thereof, particularly relating to a kind of is medicine of making of raw material and preparation method thereof with the vegetable Chinese herbal medicine extract, and especially relating to a kind of is medicine that improves carbohydrate tolerance and treatment diabetes and obesity of making of raw material and preparation method thereof with the vegetable Chinese herbal medicine extract.
Background technology
Obesity is a medical problem, is a kind of disease.Existing a large amount of evidences show that obesity and hypertension, hyperlipidemia, diabetes, cardiovascular and cerebrovascular disease, breast carcinoma and infertility etc. have dependency in various degree (to see Fig. 1, wherein abscissa is the constitutional index BMI that weighs obese degree, and vertical coordinate is the onset risk of four kinds of diseases).World Health Organization (WHO) formally was defined as obesity a kind of disease in 1997, was referred to as obesity.Human beings'health and life-span in obesity itself and the disease serious threat relevant with obesity.Along with the westernization of development of Chinese economy and life style, the incidence rate of Chinese obesity also rises year by year, and the Beijing area adult is overweight and the obesity patient surpasses 40%.China 24.5 ten thousand census of population results show, with BMI (Body Mass Index) greater than 28.0 as the obesity diagnostic criteria, national population of being obese about 7,000 ten thousand.Present existing 61% adult is overweight in the U.S., has every year 300000 people to die from the disease that is caused by obesity.About 10,000,000,000 yuans of the total cost that China is used to lose weight every year and obesity-related disease is treated, the U.S. is 1,000 hundred million dollars.
Diabetes and obesity are to concern two kinds of very close endocrine metabolism diseases, the two relation of reciprocal causation sometimes.According to recent statistics, whole world diabetics sum is about 2.5 hundred million at present, and China is about 50,000,000.Whole world diabetics number is with very fast speed increment.The essence of diabetes and obesity is carbohydrate, protein-based and lipoid material Metabolic disorder.This three major types material is to transform mutually in vivo, these conversions are subjected to the regulation and control of various enzymes, the activity of enzyme is subjected to various hormonal regulation in the body, and the secretion of hormone then relates to the function of various bodies of gland in the body, so obesity, II-type diabetes are also referred to as endocrinopathy.The activity of enzyme also is subjected to the adjusting of xenobiotic except that being subjected to hormonal regulation, as the inhibitor or the activator of various enzymes.Seek the inhibitor and the activator of the enzyme relevant, become the important means of new drug development with specified disease.The western countries that with the U.S. are representative are that the exploitation of slimming medicine has dropped into a large amount of funds over nearly 20 years, succeeded in developing several representative appetrol (as shown in table 1), hypoglycemic medicine mainly contains insulin preparation, yellow ureide derivative chemical compound, biguanide compound and glucosidase inhibitor four classes (as shown in table 2).
Table 1: world's slimming medicine development situation
Table 2: world's hypoglycemic medicine development situation
The effect of weight reducing of Chinese medicine (natural drug) is sure, and the Chinese herbal medicine of putting down in writing in the classic of TCM at all times with fat-reducing and antihyperglycemic just has nearly hundred kinds.The diet products that with the Chinese herbal medicine are raw material all are the health foods based on traditional Chinese medical theory, exist all generally that dosage is big, dosage form is not too convenient, active component is very not clear and definite, the machine-processed problem such as not really clear of modern pharmacology, these also are modernization of Chinese medicine key problem in technology to be solved.
The innovation and creation content
The purpose of this invention is to provide a kind of medicine that can effectively improve carbohydrate tolerance and treatment diabetes and obesity.
The medicine that improves carbohydrate tolerance and treatment diabetes and obesity provided by the present invention comprises at least two kinds in Semen Cassiae extract, guava extract and the Calyx Seu Fructus Physalis extract.
Described Semen Cassiae extract is flavone compound and anthraquinone analog compound; Described guava extract is a polyphenol compound; Described Calyx Seu Fructus Physalis extract is a glycoside compound.
According to Semen Cassiae extract, guava extract and the Calyx Seu Fructus Physalis extract different compatibilities between mutually, the composition of described medicine has following several:
1) be made up of Semen Cassiae extract and guava extract, their ratio of weight and number is Semen Cassiae extract: guava extract=1:0.1-10.
2) be made up of Semen Cassiae extract and Calyx Seu Fructus Physalis extract, their ratio of weight and number is Semen Cassiae extract: Calyx Seu Fructus Physalis extract=1:0.1-10.
3) be made up of guava extract and Calyx Seu Fructus Physalis extract, their ratio of weight and number is guava extract: Calyx Seu Fructus Physalis extract=1:0.01-100.
4) be made up of Semen Cassiae extract, guava extract and Calyx Seu Fructus Physalis extract, their ratio of weight and number is a Semen Cassiae extract: guava extract: Calyx Seu Fructus Physalis extract=1:0.1-10:0.1-10 wherein is preferably 9:6:5.
When needing, in said medicine, can also add one or more pharmaceutically acceptable carriers.Described carrier comprises diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.; Can also add flavouring agent, sweeting agent etc. in case of necessity.
Medicine of the present invention can be made various ways such as injection, tablet, powder, granule, capsule, oral liquid, unguentum, cream.The medicine of above-mentioned various dosage forms all can be according to the conventional method preparation of pharmaceutical field.
It is 7 to 30 days that the consumption of said medicine is generally 2-50mg/KgBW/day course of treatment.
Second purpose of the present invention provides a kind of above-mentioned method of improving carbohydrate tolerance and treatment diabetes and obesity drug for preparing.
Improve the preparation method of the medicine of carbohydrate tolerance and treatment diabetes and obesity, may further comprise the steps:
1) with the method for hydrophilic organic solvent backflow, extraction, Acid precipitation, be raw material with the Semen Cassiae, the preparation Semen Cassiae extract; With the method for water extraction, microfiltration and ultrafiltration molecular retention, be raw material with leaf or the fruit of Fructus psidii guajavae immaturus, the preparation guava extract; With the method for hydrophilic organic solvent backflow, column chromatography for separation, be raw material with Calyx Seu Fructus Physalis herb, fruit or peel, the preparation Calyx Seu Fructus Physalis extract;
2) two kinds in Semen Cassiae extract, guava extract and the Calyx Seu Fructus Physalis extract are mixed the medicine of improve carbohydrate tolerance and treatment diabetes and obesity at least; When described medicine was made up of Semen Cassiae extract and guava extract, their ratio of weight and number was Semen Cassiae extract: guava extract=1:0.1-10; When described medicine was made up of Semen Cassiae extract and Calyx Seu Fructus Physalis extract, their ratio of weight and number was Semen Cassiae extract: Calyx Seu Fructus Physalis extract=1:0.1-10; When described medicine was made up of guava extract and Calyx Seu Fructus Physalis extract, their ratio of weight and number was guava extract: Calyx Seu Fructus Physalis extract=1:0.01-100; When described medicine was made up of Semen Cassiae extract, guava extract and Calyx Seu Fructus Physalis extract, their ratio of weight and number was a Semen Cassiae extract: guava extract: Calyx Seu Fructus Physalis extract=1:0.1-10:0.1-10.
Be that the ethanol of 40%-80% carries out reflux, extract, with concentration during described preparation Semen Cassiae extract, extract with alkali.When described preparation Fructus psidii guajavae immaturus was extracted, the temperature of water extraction was 85-95 ℃.Be that the ethanol of 40%-80% carries out reflux, extract, with concentration during described preparation Calyx Seu Fructus Physalis extract.
The used Semen Cassiae of the present invention is the dry mature seed of the blunt leaf Semen Cassiae of leguminous plant (Cassia obtusifolia L.), can give birth to and use or stir-fry usefulness, has another name called Semen Cassiae.Effect is a liver heat removing and eyesight improving, loosening bowel to relieve constipation.It is dizzy to can be used for the treatment headache, conjunctival congestion and swelling pain, constipation with heat retention.Fructus psidii guajavae immaturus is leaf and the fruit of Punicaceae plant Fructus psidii guajavae immaturus (Psidium guajava L.).The Fructus psidii guajavae immaturus nature and flavor are sweet, puckery, flat, and function is an astringing to arrest diarrhea, anti-inflammation hemostasia.Cure mainly: acute chronic enteritis, diarrhoea, infantile dyspepsia and bacillary dysentery.Osteopatia sprain, traumatic hemorrhage, ecthyma disunion of a specified duration etc. are controlled in bright leaf external.Calyx Seu Fructus Physalis is dry herb, fruit and the peel of plant of Solanaceae Calyx Seu Fructus Physalis (Calyx seu fructus P.).
The source of above-mentioned three kinds of Chinese medicines is very extensive, and distribution is all arranged all over the world, for a large amount of, the cheap production of medicine of the present invention provides assurance.
The theory of applied chemistry genomics of the present invention and method, the synthetic rate-limiting enzyme FAS activity of expression, fatty acid and polysaccharide decomposing enzyme α-amylase activity with adipose cell differentiation specific expression gene PPAR γ 2 are target spot, screen 100 various plants extracts, obtained prescription of the present invention; This medicine has inhibition α-amylase activity and suppresses the active effect of fatty acid synthetase, zoopery and crowd's evidence prescription of the present invention not only have the effect of significant reduction body weight to high-fat adiposity rat and obese people, simultaneously hyperglycemia mice and the low crowd of carbohydrate tolerance and diabetics are had significant reduction post-prandial glycemia and improve the carbohydrate tolerance effect, obvious to the effect of the concurrent diabetics blood sugar lowering of obesity; Simultaneously, do not see dizziness arranged, feel sick, the common side effect of appetrol class such as diarrhoea, local discomfort, gastrointestinal reaction, hypoglycemia, lacticemia, constipation; The present invention lays a good foundation for the research and development of China's slimming medicine, has important theory and practice significance.
Description of drawings
Fig. 1 is the sketch map that concerns between obesity and diabetes and other diseases;
Fig. 2 is the preparation technology of Semen Cassiae extract;
Fig. 3 is the preparation technology of guava extract;
Fig. 4 is the preparation technology of Calyx Seu Fructus Physalis extract;
Fig. 5 is the antiobesity action curve of medicine of the present invention to obese rat;
Fig. 6 is the antiobesity action curve of medicine of the present invention to obese rat;
Fig. 7 is the antiobesity action curve of medicine of the present invention to obese rat;
Fig. 8 is the antiobesity action curve of medicine of the present invention to obese rat.
The specific embodiment
Embodiment 1: the preparation of medicine of the present invention
(1) preparation of Semen Cassiae extract
As shown in Figure 2, depend on pine torch powder 50kg, reflux with the ethanol of 800 liters (500--1000 rise all can) 70%, ethanol extract is dissolved in ether after concentrating, with concentration the be 10% sodium bicarbonate extraction of (5-20% all can), aqueous solution salt Acid precipitation must Semen Cassiae extract 0.5kg.
(2) preparation of guava extract
As shown in Figure 3, get dry Folium Psidii Guajavae 50kg, extract 2 times under 90 ℃ of conditions with 1000kg water, the centrifugal 15min of extracting solution 2000rpm keeps supernatant, carries out microfiltration with semipermeable membrane, supernatant carries out the ultrafiltration secondary with semipermeable membrane, supernatant after the ultrafiltration obtains the cream powder behind concentrating under reduced pressure, through drying under reduced pressure, obtain guava extract 0.5kg.
(3) preparation of Calyx Seu Fructus Physalis extract
As shown in Figure 4, get Calyx Seu Fructus Physalis herb 50kg, 800 liters of (500--1000 rise all can) 40% ethanol, reflux, extract, 2hr under 55 ℃ of conditions obtains crude extract, and concentrating under reduced pressure under 55 ℃ of conditions obtains concentrated solution, with concentrated solution AI
2O
3The chromatographic column of filling separates, 60% ethanol elution, and pregnant solution is freezing or vacuum drying behind concentrating under reduced pressure under 55 ℃ of conditions, obtains Calyx Seu Fructus Physalis extract 0.5kg.
Embodiment 2: the acute toxicity testing of Semen Cassiae extract, guava extract and Calyx Seu Fructus Physalis extract
Get each 60 of kunming mices and be divided into 3 groups, each 10 of every group of male and female, by (body weight 65kg) the 2.7g Semen Cassiae extract for each person every day of being grown up, or guava extract, or the calculating of Calyx Seu Fructus Physalis extract dose, be converted into per kilogram of body weight 41.5mg every day, enlarge the administration of 100 times of disposable per os mouse stomaches with this dosage, in two weeks, observe and record poisoning symptom and death condition, calculate LD
50The result proves: 1. do not find poisoning symptom and death condition; 2. female, male mice acute oral LD
50All greater than 41500mg/KGBW.Judge that according to acute toxicity grading criteria in " toxicological evaluation of food safety procedure and method " Semen Cassiae extract, guava extract and Calyx Seu Fructus Physalis extract all belong to the non-toxic type material.
Embodiment 3: the fat-reducing effect of medicine of the present invention
With the ratio of weight and number is the Semen Cassiae extract of 9:6:5, the pharmaceutical composition of guava extract and Calyx Seu Fructus Physalis extract, press 0.3g/ people/sky, 1.0g/ people/sky and 2.7g/ people/three Rapid Dose Calculation in sky, be converted into per kilogram of body weight 4.6mg every day, 15.4mg and 41.5mg, enlarge 100 times of disposable per os obese rat of feeding with this dosage, rat body weight changes in around the record, the result as shown in Figure 5, show that various dosage all have fat-reducing effect, wherein dosage is that the fat-reducing effect in 1.0g/ people/sky and 2.7g/ people/sky is better, and the fat-reducing effect in 0.3g/ people/sky is general.
Embodiment 4: the fat-reducing effect of medicine of the present invention
With the ratio of weight and number is the Semen Cassiae extract of 2:1, the pharmaceutical composition of guava extract, press 2.7g/ people/sky Rapid Dose Calculation, be converted into per kilogram of body weight 41.5mg every day, enlarge 100 times of disposable per os obese rat of feeding with this dosage, rat body weight changes in around the record, the result shows that medicine of the present invention has fat-reducing effect preferably under this dosage as shown in Figure 6.
The fat-reducing effect of embodiment 5, medicine of the present invention
With the ratio of weight and number is the Semen Cassiae extract of 5:1 and the pharmaceutical composition of Calyx Seu Fructus Physalis extract, press 2.7g/ people/sky Rapid Dose Calculation, be converted into per kilogram of body weight 41.5mg every day, enlarge 100 times of disposable per os obese rat of feeding with this dosage, rat body weight changes in around the record, the result shows that medicine of the present invention has fat-reducing effect preferably under this dosage as shown in Figure 7.
The fat-reducing effect of embodiment 6, medicine of the present invention
With the ratio of weight and number is the guava extract of 2:3 and the pharmaceutical composition of Calyx Seu Fructus Physalis extract, press 2.7g/ people/sky Rapid Dose Calculation, be converted into per kilogram of body weight 41.5mg every day, enlarge 100 times of disposable per os obese rat of feeding with this dosage, rat body weight changes in around the record, the result shows that medicine of the present invention has fat-reducing effect preferably under this dosage as shown in Figure 8.
The blood sugar decreasing effect of embodiment 7, medicine of the present invention
With ratio of weight and number is Semen Cassiae extract, guava extract and the Calyx Seu Fructus Physalis extract of 9:6:5, fully mixes filled capsules.The capsule specification is No. 0, the 0.45g/ grain.By adult (70kg) 2.7g (6) metering for each person every day, be converted to the kg body weight dosage of hyperglycemia mice, make suspension, the per os gastric infusion, once a day, continuous 21 days.Measure administration front and back mouse blood sugar, the result is as shown in table 3, shows to reduce about 30% post-prandial glycemia.
Table 3: medicine of the present invention is to the influence of mice level of postprandial blood sugar
*p<0.01
The blood sugar decreasing effect of embodiment 8, medicine of the present invention
With ratio of weight and number is guava extract and the Calyx Seu Fructus Physalis extract of 13:7, fully mixes filled capsules.The capsule specification is No. 0, the 0.45g/ grain.9 routine II-diabetes mellitus types are divided into experimental group (5 example) and matched group (4 example), and administration also detects administration front and back blood glucose.By 2.7g (be 6 of every days, divide and take for 3 times, each 2) administration for each person every day, continuous 24 days.Measure administration front and back blood sugar level, the result is as shown in table 4, shows to reduce II-diabetes mellitus type post-prandial glycemia of about 26%.
Table 4: medicine of the present invention is to the influence of II-diabetes mellitus type level of postprandial blood sugar
*p<0.01
Claims (1)
1, a kind of appetrol are made up of Semen Cassiae extract and Calyx Seu Fructus Physalis extract, and their ratio of weight and number is Semen Cassiae extract: Calyx Seu Fructus Physalis extract=5:1; Wherein, described Semen Cassiae extract is to be raw material with the Semen Cassiae, and adopt following method preparation: the ethanol with 70% refluxes, ethanol extract is dissolved in ether after concentrating, and is that 5-20% sodium bicarbonate extracts Acid precipitation with concentration; Described Calyx Seu Fructus Physalis extract is to be raw material with Calyx Seu Fructus Physalis herb, fruit or peel, adopts following method preparation: reflux reuse Al with 40% ethanol earlier
2O
3The chromatographic column of filling separates 60% ethanol elution.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US7611739B2 (en) * | 2006-01-06 | 2009-11-03 | Amerilab Technologies, Inc. | Method of using guava extract and composition including guava extract |
| US20090004270A1 (en) | 2006-01-06 | 2009-01-01 | Amerilab Technologies, Inc. | Method of using guava extract |
| CN101129604B (en) * | 2007-08-31 | 2010-05-26 | 哈尔滨医科大学 | Antihypelipidemic traditional Chinese medicine producing method |
| CN103432280A (en) * | 2013-08-17 | 2013-12-11 | 广州市云桥生物科技有限公司 | Composition consisting of effective traditional Chinese medicine parts and used for treating obesity |
| CN104667248A (en) * | 2015-03-21 | 2015-06-03 | 陈梦佳 | Glucose-lowering capsule and preparation method thereof |
| CN109223902A (en) * | 2018-11-15 | 2019-01-18 | 上海市松江区方松街道社区卫生服务中心 | It is a kind of for intervening the Chinese medicine composition of prediabetes crowd |
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Non-Patent Citations (4)
| Title |
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| 中药药剂学. 张兆旺，119－120，中国中医药出版社. 2003 |
| 中药药剂学. 张兆旺，119－120，中国中医药出版社. 2003 * |
| 浅谈膜分离技术及其在制药工业的应用. 崔茹珍.医药工业设计，第4期. 1997 |
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