CN1181836C - Chinese medicine composition for treating diabetes and its preparing process - Google Patents
Chinese medicine composition for treating diabetes and its preparing process Download PDFInfo
- Publication number
- CN1181836C CN1181836C CNB011183209A CN01118320A CN1181836C CN 1181836 C CN1181836 C CN 1181836C CN B011183209 A CNB011183209 A CN B011183209A CN 01118320 A CN01118320 A CN 01118320A CN 1181836 C CN1181836 C CN 1181836C
- Authority
- CN
- China
- Prior art keywords
- rhizoma coptidis
- chinese medicine
- extract
- alkaloid
- total alkaloids
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
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Abstract
The present invention belongs to the field of the research and the development of new Chinese medicines, which relates to a method of using modern science and technology to extract and refine active components of a traditional Chinese medicine coptis chinensis, and also provides the preparation formulation dosage forms of the Chinese medicine preparation, particularly an oral capsule. The extracted active components, namely total alkaloids of coptis containing berberine hydrochloride as the main component, are first used for diabetes treatment, and are especially effective in gastropyretic diabetes treatment.
Description
The present invention relates to a kind of Chinese medicine pharmaceutical composition for the treatment of diabetes, relating in particular to the Rhizoma Coptidis total alkaloids that is contained in the Chinese medicine Rhizoma Coptidis is the Chinese medicine preparation of its effective ingredient, this medicine produces effect to treatment of diabetes, and the present invention also provides a kind of preparation method of this medicine.
Diabetes are a kind of common endocrine---metabolic diseases, it distributes all in the whole world, and be the trend that increases gradually, the prevalence of China's diabetes has reached 10.15%, though it is higher than not with developed countries, but it is because populous, had second largest in the world diabetics crowd, be only second to the U.S., and just with per speed increment that doubled in 15 years, China's diabetics is based on the II type, but the many concealments of its morbidity, complication is often more serious, in carbohydrate metabolism disturbance often with lipometabolic disorder and hemorheological unusual, so atherosclerosis and microangiopathies take place in patient easily, early stage lose control or therapeutic effect bad, pathological changes can be involved health multisystem organ, has a strong impact on patient's life-span and life quality, therefore control is sugared, fat metabolic disturbance, what prevent and treat complication is the emphasis for the treatment of diabetes.Therefore, seek effective blood sugar lowering, blood fat reducing, the hemorheological medicine of improvement and become current urgent research topic.
This product is the dry rhizome of ranunculaceae plant Rhizoma Coptidis Coptis chinensis Franch.Excavate autumn, removes fibrous root and silt, and drying is hit residual fibrous root.2000 editions Rhizoma Coptidis of recording of Chinese Pharmacopoeia have three kinds: Rhizoma Coptidis (Coptis chinensis Franch), triangle leaf connect (Coptis deltoidea C.Y.cheng et Hsiao) and Coptis Teeta Wall (Coptisteeta wall).They have heat clearing and damp drying, the effect of eliminating fire and detoxication.By a large amount of pharmacological testings, determine that Rhizoma Coptidis is the crude drug of this Remedies for diabetes.
Rhizoma Coptidis is a Ranunculaceae coptis plant Coptis chinensis Franch rhizome.This kind is perennial herb, and main morphological characteristic is that multi-branched gathers cluster, likeness in form chicken feet, or single bending, Dan Zhichang 3～9cm, diameter 3～8mm.The surface yellowish-brown is to lark, and is coarse, and irregular nodositas protuberance is arranged, visible fibrous root or vestiges, and shape is as like a chain of pearls or a string of beads, and the part internode is level and smooth.Brown scale leaf residue is arranged at top.Matter is hard, and section is irregular, and skin zone's burgundy or orange red has Flos Chrysanthemi shape texture, the hollow that the marrow of the little shape of central visible red brown has
[1], feeble QI, flavor are extremely bitter.Gathering and processing this medical material of commonly using is underground rhizome, cleans and pulverizes.
The Rhizoma Coptidis bitter in the mouth, cold in nature.GUIXIN, spleen, stomach, liver, gallbladder, large intestine channel.Function heat clearing and damp drying, eliminating fire and detoxication.But clearing away stomach-heat, eliminating heart-fire.Said " Rhizoma Coptidis is controlled and quenches one's thirst ... can rush down the fire of upper, middle and lower three warmers, and fire goes then body fluid not have to fry in shallow oil, quench one's thirst from ending as " hundred drug effect wonders ".”。The Rhizoma Coptidis beginning is stated from " refreshing slave's book on Chinese herbal medicine warp ": " the Rhizoma Coptidis bitter in the mouth is nontoxic, cures mainly steam.”。" Mingyi Bielu) " said: " main the five internal organs are cold and hot, let out under for a long time and ward off pus and blood, only quench one's thirst." " medicine origin volume under medication be equipped with purport " then spell out: " burnt wet and pain use Rhizoma Coptidis in going, and the eliminating heart-fire event is also ... ".The Compendium of Material Medica speech " is controlled and is quenched one's thirst, steam Rhizoma Coptidis with wine." cure mainly " steam ..., it is frightened only to quench one's thirst "." channel syndrome card medicine record volume 13 " say " Rhizoma Coptidis goes into stomach, the hardship heart that gets ahead, last removing pathogen in the heart and under reinforce the kidney, in dry and other clear wood, the heresy that the five internal organs are damp and hot, non-this can not in let out also "
It is documented, the master contains berberine (berberine) 5%～8% in the Rhizoma Coptidis medical material rhizome, also contains coptisine (coptisine), 13-methyl-.psi.-coptisine. (worenine), palmatine (palmatine), jateorhizine (jatrorrhizine), table coptisine (epiberberine), groenlandicine and berberastine (berberastine) etc.; Because they have analog structure, often are referred to as Rhizoma Coptidis alkaloid.In addition, still contain magnoline (magnoflorine) and ferulic acid (ferulicacid), chlorogenic acid etc.
Other, also contain 3-(3 ', 4 '-dihydroxy phenyl)-(2R)-lactic acid, 3-(3 ', 4 '-dihydroxy phenyl)-(2R)-lactic acid-4 '-O-glycoside, 3 ', 4 '-dihydroxy benzenes ethyl alcohol-1-O-β-D-glycoside (3 ', 4 '-dihydroxyphenethyl alcohol-1-O-β-D-glucopyranoside), gentisic acid-5-O-β-D-glycoside (gentisic acide-5-O-β-D-glucpyranoside), 4-O-Resina Ferulae acyl-D-quininic acid (4-O-feruloyl-D-quinic acid), 5-O-Resina Ferulae acyl-D-quininic acid etc.
[1]
And the effective site that is used for treating diabetes by the isolation identification to composition in this effective site, has obtained 3 chemical compounds for extract the exquisite Rhizoma Coptidis total alkaloids that forms from Rhizoma Coptidis.See the following form:
Chemical constituent in table one Rhizoma Coptidis total alkaloids
| Sequence number | Chinese | English name |
| 1 | Berberine | Berberine |
| 2 | Jatrorrhizine chloride | Jatrorrhizine Hydrochloride |
| 3 | Fibrauretin | Palmatine |
According to the pharmacopeia record, the extract of Rhizoma Coptidis has the effect of heat clearing and damp drying, eliminating fire and detoxication, and diseases such as hypertension, diabetes, hyperlipidemia are had certain curative effect.In traditional tcm therapy, can only be to take behind the decocting, this traditional method one is to be difficult at utmost bring into play drug effect, says from another point of view, the inconvenience of taking of Chinese medicine has been known.By the drug efficacy study to effective ingredient in the Chinese medicine, and then realize extraction and utilization to this natural component, produce be equal to even be better than synthetic drug on drug effect, and be lower than the pure Chinese medicinal preparation of synthetic drug on toxicity, this is the development to traditional medicine.
The object of the present invention is to provide a kind of Chinese medicine pharmaceutical composition for the treatment of diabetes, effective ingredient wherein is the alkaloid compound from the Chinese medicine Rhizoma Coptidis, also claims Rhizoma Coptidis extract.
Having the present invention further provides with described Rhizoma Coptidis alkaloid extract is active component, is used for the treatment of the pure Chinese medicine pharmaceutical preparation and the related dose forms of diabetes.
Another object of the present invention is to be provided for to treat the preparation method of preparation method, particularly Rhizoma Coptidis extract of this pure Chinese medicine medicine of diabetes.
Pharmaceutical composition provided by the invention, it contains the ethanol extraction that obtains from the Rhizoma Coptidis crude drug, comprised Rhizoma Coptidis total alkaloids in the composition of this extract, main active wherein is a Rhizoma Coptidis total alkaloids, from the pharmacodynamics angle, be used for the treatment of the pharmaceutical composition of diabetes as the present invention, the content of the Rhizoma Coptidis total alkaloids in the described Rhizoma Coptidis extract preferably is not less than 55% more than 65%.
On this basis, the present invention has has also researched and proposed a kind of pure Chinese medicine pharmaceutical preparation for the treatment of diabetes, and this Chinese medicine medicine is the effective active composition with above-mentioned Rhizoma Coptidis extract, and has comprised acceptable auxiliary component on the pharmaceutics.
Pharmaceutical preparation of the present invention comprises injection and oral agents, wherein oral agents comprises capsule, oral liquid, tablet, granule etc., injection, particularly capsule require the amount of Rhizoma Coptidis total alkaloids in its effective ingredient to be not less than 65%, preferably are not less than 55%.
The present invention also provides a kind of preparation method of this pure Chinese medicine pharmaceutical preparation, and it comprises: be raw material with the Rhizoma Coptidis, use ethanol extraction, and purified separation produces Rhizoma Coptidis extract, the content that makes Rhizoma Coptidis total alkaloids in this extract is more than 65%; With this Rhizoma Coptidis extract is effective ingredient, is prepared into the pharmaceutical preparation of requirement according to practice of pharmacy.
The Rhizoma Coptidis crude drug generally is to excavate autumn, removes fibrous root and silt, and drying is hit residual fibrous root.Should pulverize earlier before being used for extraction, require by the 20-40 mesh sieve usually, being beneficial to wherein, effective ingredient is fully extracted.Consider that from the production angle in the Rhizoma Coptidis medical material that the present invention selects for use, the total alkaloid content that has comprised above-mentioned various Rhizoma Coptidis total alkaloids chemical compounds is with berberine hydrochloride (C
20H
18NO
4.HCl) meter should be not less than 7%.
According to the embodiment of comparative optimization of the present invention, the method for extracting the Rhizoma Coptidis total alkaloids extract comprises that the following step poly-:
(1) extracts the Rhizoma Coptidis crude drug 3 times with the above alcohol heating reflux of 80% concentration;
This ethanol extract of concentrating under reduced pressure to relative density below (2) 60 ℃ is the concentrated solution of 1.05 (25 ℃ of mensuration);
(3) above-mentioned concentrated solution is filtered, it is between 2～3 that filtrate is regulated pH value with concentrated hydrochloric acid, leaves standstill 6 hours, filters.
(4) with filter cake drying under reduced pressure (70 ℃), be ground into fine powder and get alkaloid I.
(5) again filtrate is crossed 724 type weak-acid cation-exchange resin posts, washing.
(6) wash resin column with 6% ammonia alcoholic solution, eluent is through concentrating under reduced pressure, and vacuum drying gets alkaloid II.
(7) alkaloid I and alkaloid II mix homogeneously are got Rhizoma Coptidis total alkaloids.
In the said extracted step, concentration of ethanol can not be less than 80%, consider from the angle that improves extraction ratio, concentration of ethanol is high more good more, from producing and the consideration of cost angle, the preferred ethanol of about 80% concentration that uses carries out the extraction of raw material, and extracting method is a reflux, or other feasible mode of operation, should keep bigger ratio between ethanol and the crude drug, to guarantee the complete of extraction, can use about 8-10 alcoholic solution reflux (general reflux, extract, 3 times) doubly of raw material weight, available percolation and circumfluence method, the preferred employing refluxed, get the Rhizoma Coptidis medicinal powder, extract each 1 hour 3 times with 10 times of amount 80% alcohol heating reflux.Filter, with the ethanol extract decompression recycling ethanol, it is 1.05 (25 ℃ of mensuration) that extracting solution is concentrated into relative density, filter, it is between 2～3 that filtrate is regulated pH value with concentrated hydrochloric acid, leaves standstill 6 hours, filter, will precipitate drying under reduced pressure (70 ℃), be ground into fine powder and get alkaloid I.Again filtrate is crossed 724 type weak-acid cation-exchange resin posts, washing, remove neutrality and acid impurities, the alkaloid cation that is adsorbed, ammonia alcoholic solution desorbing with 6%, eluent is through concentrating under reduced pressure, and vacuum drying gets alkaloid II, and alkaloid I and alkaloid II mix homogeneously are got Rhizoma Coptidis total alkaloids.
For helping the separation of effective ingredient, extracting solution after concentrating need reach certain volume and acid-base value, the optimized technical scheme according to the present invention, extracting liquid volume should be concentrated into 1 times of medical material weight, pH value transfers between 2～3 with hydrochloric acid, the content of berberine and the rate of transform are higher under this pH value, the berberine in the ethanol extract fully can be precipitated out; And the water-soluble alkaloid salt hydrochlorate of the energy in the supernatant can utilize the characterization of adsorption of cation exchange resin to be separated.The alkaloid salt hydrochlorate is adsorbed on earlier on 724 cation exchange resiies, after impurity separates, with the pure desorption of 6% ammonia, obtains Jatrorrhizine chloride and fibrauretin again.And the adsorption capacity of 724 cation exchange resiies has certain limit.In optimized technical scheme of the present invention, we select the carrying capacity of 724 cationic exchange resin adsorption Rhizoma Coptidis alkaloid II to be: 2.20g Rhizoma Coptidis alkaloid II/100g resin.The desorption flow velocity of liquid also has certain influence to alkaloidal yield, and the flow velocity of the liquid that we select is: 0.6ml/cm
2.min, to avoid the loss of effective ingredient, guarantee the stability of technology; In addition, consider that from cost and efficient aspect we have also carried out the investigation of eluant consumption, with 6% ammonia alcohol of the preferred 7 times of volumes of the present invention with 0.6ml/cm
2.min speed eluting.
According to technical scheme of the present invention, this Chinese medicine preparation dosage form can be injection or oral formulations, and wherein oral formulations comprises capsule, oral liquid, tablet, granule etc.When the preparation oral formulations, the auxiliary type agent of selecting for use can be conventional fillers such as starch, dextrin or cyclodextrin, sucrose, stearate, preparation later stage preparation technology and equipment all belong to the routine techniques of pharmaceutical field, the present invention does not limit this, so will not describe in detail at this.
[embodiment one]
The preferred dosage form of the present invention is a capsule:
By prescription, take by weighing Rhizoma Coptidis total alkaloids 100g, 80 mesh sieves are crossed in the pulverizing of milling.The medical starch 100g that added 80 mesh sieves, mix homogeneously, ethanol with 65% is made soft material in right amount, crosses 35 mesh sieve system granules, oven dry, make moisture less than 5%, cross 40 mesh sieve granulate, cross 60 mesh sieves and remove fine grained, fine grained is used for the capsular preparation of next group, get 40～60 order granules, be sub-packed in capsule No. 1.Every capsules contains Rhizoma Coptidis total alkaloids 0.1g, uses aluminium plastic composite packaging, Co
60Radiation sterilization, promptly.
Creativeness of the present invention is to have gone out Rhizoma Coptidis extract by scientific and feasible method extraction separation from Rhizoma Coptidis Chinese medicine, and further this extract is prepared into the Chinese medicine preparation that is used for the treatment of diabetes as effective ingredient.As previously described, the effective ingredient of medicine provided by the invention is the Rhizoma Coptidis extract that comprises Rhizoma Coptidis total alkaloids, for reaching goal of the invention, should be to the extraction ratio of Rhizoma Coptidis total alkaloids in the crude drug more than 65%, the content of Rhizoma Coptidis glycoside also should be not less than 35% in this extract simultaneously.
For guaranteeing the quality of medicine, need in process of production the active constituent content in the final extract is detected at any time.The method that is used to detect described alkaloid compound can be by any feasible detection means and known method, and the present invention has proposed the feasible detection method of a cover at this.
At first, pass through efficient liquid phase chromatographic analysis, with the contrast of berberine hydrochloride standard substance spectrogram, proved that containing with the berberine hydrochloride is the Rhizoma Coptidis alkaloid mixture (calculate the peak area of main component from spectrogram, berberine hydrochloride accounts for about 50%) of main component in total alkaloids extract.From ultra-violet absorption spectrum, can see, berberine hydrochloride standard substance and Rhizoma Coptidis extract all have maximum absorption band at 345nm, so should think that Rhizoma Coptidis extract is consistent substantially with the ultraviolet absorpting spectrum of berberine hydrochloride, the present invention has adopted ultraviolet-visible spectrophotometry standard curve to detect total alkaloid contents roughly in view of the above; Simultaneously, adopt the high performance liquid chromatogram external standard method,, in actual production, use proof, the favorable reproducibility of testing result by the content of berberine hydrochloride in standard curve detection and the control Rhizoma Coptidis extract.Should be noted that this method only as one of quality control method of product of the present invention, should not get rid of other any method that meets the demands and operation.Particularly the extraction ratio assay of total alkaloids mixture is easy to realize for those skilled in the art, also can as above-mentioned be to indicate by contrast extract and crude drug to obtain extraction ratio of effective constituents in the total extract with the berberine hydrochloride at the light absorption value of 345nm, wherein the content of berberine hydrochloride then can record by the HPLC external standard method.
Accompanying drawing 1 is the HPLC spectrogram of berberine hydrochloride standard substance.
Accompanying drawing 2 is HPLC spectrograms of the Rhizoma Coptidis extract for preparing of the present invention.
The HPLC of Berberine hydrochloride measures in the extract
The HPLC condition:
Mobile phase: acetonitrile: 0.05mol/L sodium dihydrogen phosphate=30: 70
Detect wavelength: 277nm
Flow velocity: 1ml/ minute
1, calibration curve
Precision takes by weighing berberine hydrochloride 10.70mg, puts in the 10ml volumetric flask, and dissolve with methanol also is settled to scale, shakes up, promptly.Accurate draw solution 0.2,0.6,1.0,1.4,1.8ml, move in the 10ml volumetric flask, methanol is diluted to 10ml, be mixed with concentration and be 0.02,0.06,0.10,0.14, the methanol solution of 0.18mg/ml, respectively get 10ul and inject high performance liquid chromatograph, with concentration is abscissa, is vertical coordinate with the peak area, the drawing standard curve.
Regression equation: Y=3E+06X-47430
The range of linearity: 0.214～1.926ug
The coefficient of determination: r=0.9999
2, the mensuration of berberine hydrochloride in the Rhizoma Coptidis extract
The preparation precision of reference substance solution takes by weighing berberine hydrochloride 10mg, puts in the 10ml volumetric flask, and dissolve with methanol also is settled to scale, shakes up, promptly.
The preparation precision of need testing solution takes by weighing Rhizoma Coptidis total alkaloids 10mg, and dissolve with methanol also is settled to 50ml, promptly.
The accurate need testing solution 10ul that draws of algoscopy injects high performance liquid chromatograph, measures, promptly.
Hydrochloric berberine (the C of this product
20H
18NO
4.HCl), must not be less than 35%
For ease of understanding the present composition at the medical value aspect treatment and the prevent diabetes, the inventor uses the capsule medicament of the above method or embodiment and injection to finish the following pharmacology and the test of pesticide effectiveness:
One, acute toxicity test
Use the Wistar healthy mice, adopt oral and two kinds of administering modes of lumbar injection, measure the capsular half lethal dose (LD of Rhizoma Coptidis
65): oral is 15.64 ± 1.28g/kg, and the abdominal cavity is 8.35 ± 0.98g/kg.Oral half lethal dose is about 165 times (clinical using dosage is 100-200mg/kg) of clinical consumption.
Two, long term toxicity test
1.Wistar plant the oral long term toxicity test of rat " Rhizoma Coptidis total alkaloids "
With 180 of Wistar kind rats, body weight 70-90 gram, male and female half and half are divided into 4 groups (matched group and three dosage groups) at random, 65 of matched group and heavy dose of groups, 40 of middle dosage group and small dose group, every group of male and female half and half.The test medication is the Rhizoma Coptidis capsule of embodiment 1.
The Wistar rat is irritated stomach with 80mg/kg, 160mg/kg, three kinds of dosage of 320mg/kg, and the normal control group is irritated the distilled water of equivalent.Every day 1 time, 6 times weekly, 26 weeks of successive administration.Three dosage treated animal ordinary circumstance, food ration, body weight change, urine analysis of blood, every hematology and blood parameters, organ weights, organ coefficients, system becomes celestial and histopathologic examination, relatively not having significant difference with matched group (adds up through the t assay, p＞0.05), and all in the normal physiological scope.Pathological examination shows that matched group and each each organs and tissues of administration treated animal are the normal structure structure, does not see that drug intoxication sexually transmitted disease (STD) reason form changes.The convalescent period in 4 weeks after the drug withdrawal, observe every detection index and there is no slow toxicity.According to the result of above long term toxicity test, think that tentatively it is safe that rat " Rhizoma Coptidis total alkaloids " 320mg/kg/d irritates stomach.
2.Beagle the oral long term toxicity test of dog " Rhizoma Coptidis total alkaloids "
Give the Beagle dog with " Rhizoma Coptidis total alkaloids " three kinds of dosage 25mg/kg, 50mg/kg, 100mg/kg and irritate stomach, every day 1 time, 6 times weekly, successive administration 6 months.The general performance of three dosage treated animals, food-intake, body weight gain, electrocardiogram detect, every hematology and blood parameters, urine analysis of blood, system become celestial, organ coefficient, histopathologic examination, with the relatively more equal not statistically significant of matched group, do not see the overt toxicity reaction.1 month convalescent period after the drug withdrawal, observe above all detection indexs and there is no slow toxicity.According to the result of long term toxicity test, tentatively think Beagle dog 100mg/kg oral be safe.
Three, pharmacodynamics test
1. Rhizoma Coptidis total alkaloids is to the influence of the blood fat of hyperlipemia rat model
Get 72 of Wistar rats, administration 0d blood sampling earlier 1 time, according to serum T-CHO level be divided into normal control, model contrast, zhibituo (576mg/kg), Rhizoma Coptidis little (20mg/kg), in 6 groups of (40mg/kg), big (80mg/kg) three dosage, every group of 12 animals.Except that normal control group feed normal diet, the equal feed high lipid food of all the other rats 6d, ig administration simultaneously, normal control group model matched group ig distilled water, every day 1 time, successive administration 14d.The 1h eye socket is got blood and is surveyed blood fat respectively at 7,10, behind the 14d gastric infusion.
The result shows: Rhizoma Coptidis total alkaloids can obviously reduce serum cholesterol (TC), triglyceride (TG) and the LDL-C (LDL-C) of hyperlipemia rat model, obviously improves its serum high-density LP-cholesterol (HDL-C).
2. Rhizoma Coptidis total alkaloids is to the influence of blood glucose in diabetic rats due to the streptozotocin
Get 120 of Wistar rats, water 24h is can't help in fasting, (wherein 12 is normal control group ip 0.05mol/L citric acid solution to ip streptozotocin 80mg/kg, pH=4.5), behind the 72h (water 8h is can't help in fasting), the tail point is got blood and is surveyed blood glucose (0d), 56 of the streptozotocin rats of blood glucose＞180mg/dl are divided into by blood glucose value: model contrast, phenformin (100mg/kg), Rhizoma Coptidis total alkaloids little (20mg/kg), in 5 groups of (40mg/kg), big (80mg/kg) dosage, normal control group, each 12 animal of model control group, all the other respectively organize 11.All ig administrations, normal control group and model control group ig distilled water, every day 1 time, 12d continuously is after the administration 3,7,12d tail point gets blood and survey blood glucose.
The result shows: after the administration 3,7,12d Rhizoma Coptidis total alkaloids three dosage can obviously reduce blood glucose in diabetic rats due to the chain urea assistant element, with model control group significant difference is arranged relatively, Rhizoma Coptidis total alkaloids three dosage groups can obviously reduce the blood glucose of diabetes rat due to the chain urea assistant element.
3. Rhizoma Coptidis total alkaloids is to the influence of blood glucose in diabetic mice due to the streptozotocin
Get 120 of Kunming mouses, water 24h is can't help in fasting, get 12 and be the normal control group, all the other animals are irritated stomach streptozotocin 100mg/kg, and (the normal control group is irritated stomach 0.05mol/L citric acid solution, pH=4.5), behind the 72h (water 8h is can't help in fasting), the tail point is got blood and is surveyed blood glucose, and 56 of the streptozotocin mices of blood glucose＞200mg/dl are divided into by blood glucose: model contrast, phenformin (100mg/kg), Rhizoma Coptidis total alkaloids little (20mg/kg), in (40mg/kg), 5 groups of (80mg/kg) dosage greatly.All ig administrations, normal control group and model control group ig distilled water, every day 1 time, 12d continuously is after the administration 3,7,12d tail point gets blood and survey blood glucose.
The result shows: each dosage group of Rhizoma Coptidis total alkaloids can obviously reduce the blood sugar level of diabetic mice due to the streptozotocin, and learning by statistics to handle has significant difference.
4. Rhizoma Coptidis total alkaloids is to the influence of alloxan diabetes rats blood glucose
Get 100 of Wistar rats, male and female half and half, water 24h is can't help in fasting, gets 10 and is normal control group, all the other animal tail vein injection 60mg/kg alloxan NS solution, (normal control group tail vein injection NS 0.2ml/100g).Behind the 72h (water 8h is can't help in fasting), the tail point is got blood and is surveyed blood glucose (0d), blood glucose value is lower than 180mg/dl person rejects, 62 of modeling successes are divided into by blood glucose: model contrast, phenformin (100mg/kg), Rhizoma Coptidis total alkaloids little (20mg/kg), in (40mg/kg), 5 groups of (80mg/kg) dosage greatly.All ig administrations, normal control group, model control group ig distilled water, every day 1 time, continuous 12 days, respectively at after the administration 3,7,12d tail point gets blood and surveys blood glucose.
The result shows: each dosage group of Rhizoma Coptidis total alkaloids can obviously reduce the blood sugar level of diabetes rat due to the alloxan.
5. Rhizoma Coptidis total alkaloids is to the influence of alloxan mouse blood sugar and insulin level
Get 100 of Male Kunming strain mice, body weight 22 ± 2g, behind the fasting 24h, get 12 for outside the normal control group filling stomach NS, all the other animals are irritated stomach alloxan 200mg/kg, survey blood glucose behind the 72h, and blood glucose value is that diabetes animal model (60) is considered as 0d blood glucose greater than 180mg/dl, be divided into by blood glucose value: model contrast, insoral (100mg/), Rhizoma Coptidis total alkaloids little (20mg/kg), in 5 groups of (40mg/kg), big (80mg/kg) dosage, every group of 12 animals.Each organizes equal ig administration, normal control group and model control group ig distilled water, every day 1 time, continuous 12 days respectively at after the administration 3,7,12d tail point gets blood and surveys blood glucose (fasting 8h), the 12d eye socket is got blood, and is centrifugal, extracts serum and surveys insulin level.
The result shows: Rhizoma Coptidis total alkaloids three dosage can obviously increase alloxan diabetes mice serum insulin level, obviously reduce mouse blood sugar.
6. Rhizoma Coptidis total alkaloids is to the influence of mice carbohydrate tolerance
Get 50 of Kunming mouses, the tail point is got hematometry mouse blood sugar (for 0h blood glucose) behind the fasting 12h, by blood glucose value be divided at random model contrast, insoral (100mg/kg), Rhizoma Coptidis total alkaloids little (20mg/kg), in 5 groups of (40mg/kg), big (80mg/kg) dosage, every group of 10 animals.Equal 1 model matched group of ig administration ig distilled water, 1.0hig50% glucose 2.5g/kg after the administration, in measuring and respectively organize blood glucose for sugar back 0.5h, 1.0h, 2.0h respectively, the result carries out the t check.
The result shows: Rhizoma Coptidis total alkaloids can obviously reduce glucose induced mice blood sugar increasing, and the carbohydrate tolerance of mice obviously strengthens.
Pharmaceutical composition of the present invention has following outstanding feature:
1. high-efficiency low-toxicity
2. active ingredient is clear and definite, and is quality controllable
3. simple process is easy to industrialization
4. plant material is cheap and easy to get
5. indication is wide, and market capacity is large
Claims (8)
1, a kind of Chinese medicine composition for the treatment of diabetes, it is to make solvent with ethanol, adopts percolation, reflow method to extract the Rhizoma Coptidis extract that obtains from the Rhizoma Coptidis crude drug, it is characterized in that this extract can obtain by following method:
(1) extracts the Rhizoma Coptidis crude drug 3 times with the above alcohol heating reflux of 80% concentration;
This ethanol extract of concentrating under reduced pressure below (2) 60 ℃ is 1.05 concentrated solution to relative density;
(3) above-mentioned concentrated solution is filtered, it is between the 2-3 that filtrate is regulated pH value with concentrated hydrochloric acid, leaves standstill 6 hours, filters;
(4), be ground into fine powder and get alkaloid I with the filter cake drying under reduced pressure;
(5) again filtrate is crossed 724 type weak-acid cation-exchange resins, washing;
(6) with 6% ammonia alcoholic solution eluting resin, eluent is through concentrating under reduced pressure, and vacuum drying gets alkaloid II;
(7) alkaloid I and alkaloid II mix homogeneously are got Rhizoma Coptidis extract.
2, the described Chinese medicine composition of claim 1, the content that it is characterized in that Rhizoma Coptidis total alkaloids in this extract is more than 65%, and the content of berberine hydrochloride is more than 15%.
3, the described Chinese medicine composition of claim 1 is characterized in that the carrying capacity of 724 cationic exchange resin adsorption Rhizoma Coptidis alkaloid II is: 2.20g Rhizoma Coptidis alkaloid II/100g resin.
4, the described Chinese medicine composition of claim 1, the flow velocity of liquid is when it is characterized in that sample: 0.6ml/cm
2.min.
5, the described Chinese medicine composition of claim 1 is characterized in that ammonia alcohol with 7 times of volumes 6% is with 0.6ml/cm
2.min speed eluting.
6, a kind of Chinese medicine preparation for the treatment of diabetes is characterized in that it is made by described compositions of claim 1 and pharmaceutics acceptable auxiliary.
7, the described Chinese medicine preparation of claim 6, its dosage form comprises injection and oral formulations.
8, the described Chinese medicine preparation of claim 7, its dosage form is an oral capsule, and the content of Rhizoma Coptidis total alkaloids is more than 65% in the described Rhizoma Coptidis extract, the content of berberine hydrochloride is more than 15%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011183209A CN1181836C (en) | 2001-05-23 | 2001-05-23 | Chinese medicine composition for treating diabetes and its preparing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011183209A CN1181836C (en) | 2001-05-23 | 2001-05-23 | Chinese medicine composition for treating diabetes and its preparing process |
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| CN1386527A CN1386527A (en) | 2002-12-25 |
| CN1181836C true CN1181836C (en) | 2004-12-29 |
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| CNB011183209A Expired - Lifetime CN1181836C (en) | 2001-05-23 | 2001-05-23 | Chinese medicine composition for treating diabetes and its preparing process |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101926872B (en) * | 2009-05-08 | 2013-11-06 | 韩会民 | Chinese medicinal detoxifying myo-regeneration paste for treating diabetic foot ulcer and preparation method thereof |
| CN106420983B (en) * | 2016-11-30 | 2019-11-26 | 天津中医药大学 | Purposes of the coptis extract in the drug for preparing the lower urinary tract symptom for preventing and/or treating benign prostatic hyperplasis and its induction |
| CN108440617B (en) * | 2018-06-22 | 2020-08-11 | 成都中创蜀洋生物科技有限公司 | Method for extracting glucoside compound from coptis chinensis |
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