CN1679869A - Preparation for diabetes and its making method - Google Patents
Preparation for diabetes and its making method Download PDFInfo
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- CN1679869A CN1679869A CN 200510054695 CN200510054695A CN1679869A CN 1679869 A CN1679869 A CN 1679869A CN 200510054695 CN200510054695 CN 200510054695 CN 200510054695 A CN200510054695 A CN 200510054695A CN 1679869 A CN1679869 A CN 1679869A
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Abstract
The invention is Chinese medicine preparation of infectious external contraction high fever and production thereof, which is produced by kudzu root, glutinous rehmannia, Radix Astragali, trichosanthin, glibenclamide and etc. The invention has the functions of tonifying kidney and nourishing Yin, replenishing qi and producing thin fluid, which is used for deficiency of both qi and yin thirst-quenching disease that is more drink, more emiction, more eating, thin, tired, insomnia, glucose in urine and blood sugar rising. The medicine is provided for diabetic, especially 'upper elimination' diabete, which is carrying and taking conveniently without decocting.
Description
Technical field: the present invention is a kind of preparation for diabetes and preparation method thereof, belongs to technical field of medicaments.
Technical background: diabetes, being " diabetes " that the traditional Chinese medical science is commonly called as, is a kind of common endocrine--metabolic disease, and its sickness rate has the trend that increases year by year, be listed in the third-largest disease after cardiovascular disease and tumor in developed country, and become world medicine man stubborn problem.Many both at home and abroad at present employing chemical synthetic drugs are treated diabetes, and its short term effect is satisfied, but late result is not fully up to expectations, and toxic and side effects is big; And use the treatment by Chinese herbs diabetes, though its long-term effect is good, short-term effect is not good.
Summary of the invention: the objective of the invention is to: a kind of preparation for diabetes and preparation method thereof is provided; Among the side of the present invention, Radix Puerariae can promote that vigour, Stigma Maydis diuretic are promoted the production of body fluid, the sour and astringent convergence of Fructus Schisandrae Chinensis, Rhizoma Dioscoreae spleen reinforcing are reinforced the kidney; All medicines share, and have strengthened medicine nourishing kidney-YIN, QI invigorating and have risen the function in Tianjin.From the doctor trained in Western medicine theory, we also control blood effectively when stressing to solve diabetes polydipsia symptom, and level of sugar reaches the comprehensive General Symptoms that improves, and the generation of prevention or delaying complications of diabetes reaches in the recent period and takes stopgap measures fast, the intended purposes of effecting a permanent cure long term.The glibenclamide proportion is very low among the we in addition, avoid the issuable headache and dizzy of heavy dose of application glibenclamide, dizzy, erythra, felt sick, returned side effect such as acid, it is 01100196.8 that safety is better than application number, the nano diabetes treating preparation of mentioning in the patent disclosure material of " nano diabetes treating preparation medicine and preparation method thereof ".Our simultaneously by modern high tech method, fine condesation and suitable select, thus become a kind of small amount and special effect, exempt to fry in shallow oil easy clothes, carry taking convenience, can take for a long time for this diabetes patient, specially control the novel form of Shangxiao type diabetes.
Summary of the invention: the present invention constitutes like this: preparation for diabetes, calculate according to composition by weight, it by: Radix Puerariae 300-5000, Radix Rehmanniae 200-300, Radix Astragali 50-120, Radix Trichosanthis 300-500, Stigma Maydis 300-500, Fructus Schisandrae Chinensis 50-120, Rhizoma Dioscoreae 30-50 and glibenclamide 0.2-0.5 are prepared from.Specifically: it adds appropriate amount of auxiliary materials by Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g and glibenclamide 0.3g and is prepared from.Described preparation is all preparations that medically allow, and comprising: pill, capsule, soft capsule, tablet, granule, powder, oral liquid, drop pill, pellet or gel.
The preparation method of described preparation for diabetes: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 6～15 times of decoctings and boil 1～3 time, each 1.5～5.5 hours, filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mixes thoroughly with concentrated solution, dry, medicated powder adds glibenclamide, obtains the material of active ingredient of the present invention, doses different adjuvants then and adopts conventional method to make different preparations.
The preparation method of described preparation for diabetes can also be: get Radix Puerariae, with ethanol or water extraction, reclaim solvent, get extracting solution A, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae decoct with water extracting solution B, extracting solution A and B can adopt the method for precipitate with ethanol, column chromatography or supercritical extraction to make with extra care after merging, and concentrate, dry, add glibenclamide, obtain containing the material of active ingredient of the present invention, make different preparations with different conventional methods then.
Capsule in the described preparation prepares like this: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mix thoroughly with concentrated solution, drying is ground into fine powder, add glibenclamide, 1% sodium carboxymethyl cellulose is granulated mixing, incapsulate, promptly.
Tablet in the described preparation prepares like this: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae etc. and grinds to form fine powder, mixes drying thoroughly with concentrated solution, be ground into fine powder, add glibenclamide, mixing, make granule, drying adds 0.4% magnesium stearate, tabletting, the bag film-coat, promptly.
Granule in the described preparation prepares like this: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mix thoroughly with concentrated solution, drying is ground into fine powder, adds glibenclamide and 3% sodium carboxymethyl cellulose, mixing, make granule, drying, promptly.
Pill in the described preparation is like this preparation: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mix thoroughly with concentrated solution, be broken into fine powder, sieve, pill, add glibenclamide, with Radix Glycyrrhizae charcoal coating, drying, promptly.
Pellet in the described preparation is like this preparation: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mixes thoroughly with concentrated solution, dry, be ground into fine powder, add glibenclamide, add the starch mixing, the system soft material, extruding-round as a ball pill promptly.
Powder in the described preparation is like this preparation: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mix thoroughly with concentrated solution, add glibenclamide, be broken into fine powder, sieve promptly.
Soft capsule in the described preparation is like this preparation: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution recovery ethanol was condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and recovery ethanol concentrates makes extractum, above-mentioned two extractum mixings, and drying is ground into fine powder, adds glibenclamide, adds soybean oil, and the heating mixing incapsulates, promptly.
Drop pill in the described preparation is like this preparation: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution recovery ethanol was condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and reclaim ethanol and concentrate and makes extractum, above-mentioned two extractum mixings, drying is ground into fine powder, adds glibenclamide, adds the PEG6000 mixing, and heating splashes in the dimethicone promptly.
Gel in the described preparation is like this preparation: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution recovery ethanol was condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and recovery ethanol concentrates makes extractum, above-mentioned two extractum mixings, and drying is ground into fine powder, adds glibenclamide, adds carbomer, makes gel.
Oral liquid in the described preparation is like this preparation: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution recovery ethanol was condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and recovery ethanol concentrates makes extractum, above-mentioned two extractum mixings, and drying is ground into fine powder, adds glibenclamide, adds stevioside and antiseptic again, boils the filtration of dissolving back, adds water promptly.
Compared with prior art: the present invention has nourishing kidney-YIN, QI invigorating rises the function in Tianjin; Be used for polydipsia, polyuria, polyphagia, become thin, fatigue and lack of strength, the gas cloudy two of the difference of sleeping lumbago, glucose in urine and blood sugar increasing needs diabetess.Particularly this prescription composition is seted forth one's views and is debated disease in Western medicine, on the dialectical rationale of Chinese medicine, Chinese medicine and western medicine is had complementary advantages, add that effective dosage form improves, thereby the dosage of drug is big when having overcome traditional western medicines in treatment diabetes, decoction inconvenience, the shortcoming that the chemosynthesis medicine toxic and side effects is big; Can selectively select, use the medicine of different dosage form according to different ill crowds, make things convenient for treatment like this, be the doctor and patient scope that provides more choices; Among the side of the present invention: Radix Puerariae can promote that vigour, Stigma Maydis diuretic are promoted the production of body fluid, the sour and astringent convergence of Fructus Schisandrae Chinensis, Rhizoma Dioscoreae spleen reinforcing are reinforced the kidney; All medicines share, and have strengthened medicine nourishing kidney-YIN, QI invigorating and have risen the function in Tianjin.We are when stressing to solve diabetes polydipsia symptom, also control blood effectively, level of sugar, reach the comprehensive General Symptoms that improves, the generation of prevention or delaying complications of diabetes, reach in the recent period and take stopgap measures fast, the intended purposes of effecting a permanent cure long term: we have also reduced the ratio of glibenclamide at prescription in addition, make untoward reaction reduce.Our simultaneously by modern high tech method, fine condesation and suitable select, thus become a kind of small amount and special effect, exempt to fry in shallow oil easy clothes, carry taking convenience, can take for a long time for this diabetes patient, become a kind of novel form of specially controlling Shangxiao type diabetes.The present invention has reached the purpose of invention.
Pharmaceutical composition of the present invention has replenishing YIN and removing heat, and effects such as heat clearing and blood circulation promoting can be used for deficiency of both QI and YIN, and the diabetes due to the venation block is the treatment of diabetes and other diseases.
Through laboratory observation, pharmaceutical composition of the present invention causes that to normal mouse, glucose the hyperglycemia mice all has obvious hypoglycemic activity, and its hypoglycemic activity is compared excellent with glibenclamide.
Experimental example 1: different decoction method extracts is to the influence test of pharmacologically active
Test method:
(1) sample preparation: take by weighing two parts of medical materials by recipe quantity, decoct with water after a the mixing, decoction liquor concentrates, and is drying to obtain to close and fries in shallow oil thing; Another part single medical material decocts with water respectively, after extracting solution concentrates, and mix homogeneously, drying is ground into fine powder, adds glibenclamide, mixing, promptly.
(2) mice is 40,10 of picked at random are as the normal control group, all the other animal tail vein injection alloxan are set up hyperglycemia model, behind the 48h, be divided into 3 groups at random according to blood glucose value, be respectively model group, close decoct administration group, divide decoct administration group, gastric infusion is 7 days continuously, 1.5h socket of the eye venous blood collection is surveyed blood glucose after the last administration, and the result is as follows:
The different decoction method extract of table 1 is tested the blood sugar reducing function of hyperglycemia mice
| Group | Dosage | Blood glucose value (mmol/L) |
| The normal control group | Normal saline | ????4.35±1.03 * |
| Model control group is closed decoct administration component decoct administration group | Normal saline 0.5g/kg 0.5g/kg | ????13.78±5.41 ????6.54±1.76* ????6.11±2.01* |
Annotate:
*Compare P＜0.05 with model group
From top statistical result as can be seen, no matter divide and fry in shallow oil or close and fry in shallow oil, the two is no significant difference on pharmacologically active, considers that from extracting angle convenient to operation our first-selection is closed and fried in shallow oil.
Experimental example 2: different influences of extracting solvent to the Radix Puerariae active component
Test method:
(1) sample preparation: take by weighing 2 parts of Radix Puerariae medical materials by recipe quantity.Portion adds 70% alcohol reflux, and extracting solution reclaims ethanol, is drying to obtain ethanol extract; Another part decocts with water, and extracting solution concentrates, and is drying to obtain the decocting thing.All the other medical materials merge decocting in water, after concentrating, and mix homogeneously, drying is ground into fine powder, adds glibenclamide, mixing, promptly.
(2) mice is 40,10 of picked at random are as the normal control group, all the other animal tail vein injection alloxan are set up hyperglycemia model, behind the 48h, be divided into 3 groups at random according to blood glucose value, be respectively model group, Radix Puerariae ethanol extract administration group, Radix Puerariae water extract administration group, gastric infusion is 7 days continuously, 1.5h socket of the eye venous blood collection is surveyed blood glucose after the last administration, and the result is as follows:
The different extracting mode gained of table 2. Radix Puerariae preparation is to the blood sugar reducing function test of hyperglycemia mice
| Group | Dosage | Blood glucose value (mmol/L) |
| The normal control group | Normal saline | ????5.01±1.37 * |
| Model control group Radix Puerariae ethanol extract administration group Radix Puerariae water extract administration group | Normal saline 0.5g/kg 0.5g/kg | ????12.12±3.47 ????6.79±2.11 *????8.11±0.97 * |
Annotate:
*Compare P＜0.05 with model group
From top statistical data as can be seen, two samples all have hypoglycemic effect, but under the similarity condition, adopt the hypoglycemic amplitude of sample of alcohol reflux greater, and in order to give full play to the curative effect of medicine, we adopt the alcohol reflux Radix Puerariae.
Experimental example 3: optimize and extract back curative effect of medication investigation
Test method:
(1) sample preparation: technology 1: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution reclaimed ethanol, is condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part.Reuse 60% ethanol elution chromatographic column flows out to there being saponin, reclaims ethanol and concentrates and makes extractum, and with itself and above-mentioned two extractum mixings, drying is ground into fine powder, and the adding glibenclamide promptly.
Technology 2: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma dioscoreae and grinds to form fine powder, mixes thoroughly with concentrated solution, and drying adds glibenclamide promptly.
(2) mice is 40,10 of picked at random are as the normal control group, all the other animal tail vein injection alloxan are set up hyperglycemia model, behind the 48h, be divided into 3 groups at random according to blood glucose value, be respectively model group, close decoct administration group, divide decoct administration group, gastric infusion is 7 days continuously, 1.5h socket of the eye venous blood collection is surveyed blood glucose after the last administration, and the result is as follows:
The different preparation technology's gained preparation of table 3. is tested the blood sugar reducing function of hyperglycemia mice
| Group | Dosage | Blood glucose value (mmol/L) |
| The normal control group | Normal saline | ????3.96±0.83 * |
| Model control group technology 1 gained drug administration group technology 2 gained drug administration groups | Normal saline 8g crude drug/kg 8g crude drug/kg | ????14.07±2.96 ????6.78±3.04 *????7.02±2.31 * |
Annotate:
*Compare P＜0.05 with model group
From top statistical result as can be seen, under the situation of taking the Isodose medical material, the blood sugar reducing function of technology 1 and technology 2 products obtained therefroms is basic identical; In view of dosage forms such as the route gained intermediate preparation soft capsule of technology 2, drop pill acquire a certain degree of difficulty, and multiple dosage form demand is arranged clinically, under the prerequisite that does not change curative effect, this patent selects to use technology 1 preparation soft capsule, drop pill, oral liquid, gel.
Experimental example 4: the present composition is to the influence of normal mouse blood sugar.40 of mices are divided into 4 groups at random, 10 every group.Be respectively two dosage groups of the present composition (0.25,0.5g/kg), glibenclamide group (0.5mg/kg) and normal saline matched group.Each organize the administration of mice oral administration gavage or etc. the capacity normal saline, once a day, continuous 3d.Behind the 3rd day oral administration, got blood in the eye frame in 2 hours, survey and respectively organize blood glucose value.The result shows, two dosage groups of the present composition and glibenclamide group be for three days on end after the administration, and normal mouse blood sugar is all had the effect of obvious reduction, and relatively there were significant differences (p＜0.01) with the normal saline group.The dose-effect relationship of the present composition is remarkable, and quite the hypoglycemic activity than glibenclamide group is slightly strong under the dosage, but does not have significant difference (p＞0.05).See Table 4.
Two dosage groups of table 4. present composition and glibenclamide group are to the influence of normal mouse blood sugar
| Group | Dosage | Blood glucose value (mmol/L) |
| The normal saline group | ?????- | ????5.17±1.24 |
| Glibenclamide group present composition low dose group present composition high dose group | ????0.5mg/kg ????0.25g/kg ????0.5g/kg | ????2.56±0.38 *????2.83±1.01 *????2.62±0.84 * |
Annotate:
*Compare P＜0.05 with the normal saline group
Experimental example 5: the present composition causes the influence of hyperglycemia mouse blood sugar to glucose.40 of mices are divided into 4 groups at random, 10 every group.Be respectively two dosage groups of the present composition (0.25,0.5g/kg), glibenclamide group (0.5mg/kg) and model control group.Each organize the administration of mice oral administration gavage or etc. the capacity normal saline, once a day, continuous 4d.1h respectively organizes mouse peritoneal injectable dextrose monohydrate 2g/kg behind the 4th day oral administration, gets blood in the eye frame behind the 1h, surveys and respectively organizes blood glucose value.
The result shows that two dosage groups of the present composition and glibenclamide group cause that to glucose the hyperglycemia mouse blood sugar all has the effect of obvious reduction, and relatively there were significant differences (p＜0.01) with model group.
Two dosage groups of the present composition are than the hypoglycemic activity of glibenclamide group excellent (p＞0.05).See Table 5.
Two dosage groups of table 5 present composition and glibenclamide group cause influence (n=10, the x ± s) of hyperglycemia mouse blood sugar to glucose
| Group | Dosage | Blood glucose value (mmol/L) |
| Model control group glibenclamide group present composition low dose group present composition high dose group | ????25ml/kg ????0.5mg/kg ????0.25g/kg ????0.5g/kg | ????14.12±3.21 ????7.54±2.38 *????7.21±2.71 *????5.34±1.09 *△ |
Annotate:
*, compare P＜0.01 with model control group; △ compares P＜0.05 with the glibenclamide group
Experimental example 6: adjuvant screening; Selecting suitable adjuvant in the present patent application for use is one of key technology of the various different dosage forms of preparation; Because adjuvant has bigger influence to various different dosage forms; Select the improper preparation and the end product quality that can influence product.
Measure to adopt the dump box method angle of repose: fill fine powder in rectangular box, its Strobilus Pini degree is suitable, till box is progressively tilted to micropowder and begins to flow out.The angle that box tilts is angle of repose.If the result is mobile poor, easily loose greater than 45%.
The hygroscopicity experiment: get test sample, about 2g puts in the weighing botle, and accurate the title decides, the weighing bottle cap is opened, put into relative humidity respectively and be 92% environment, in 25 ℃ of constant incubators, placed 84 hours, take out weighing botle, add a cover the accurate title in back and decide, calculate the moisture absorption percentage rate.The low more explanation of result value is difficult for moisture absorption.
Check disintegration: adopting changes the basket method, and lift disintegration tester, tablet are got 6, and capsule is got 6, observes in 30 minutes the situation by screen cloth.Pill is obtained ball, observes in 60 minutes the situation by screen cloth.Percent of pass height then disintegrative is good, more pleasant bulk absorption.
The capsule adjuvant
Starch slurry arabic gum sodium carboxymethyl cellulose
Consumption 1% 3% 5% 1% 5% 10% 1% 2% 4%
50 ° 45 ° 40 ° 50 ° 45 ° 40 ° 42 ° 39 ° 40 ° of angle of reposes
Hygroscopicity tests 27% 26% 29% 30% 33% 28% 22% 21% 19%
Disintegration 322121011
(not by the screen cloth number)
The granule adjuvant
Gelatine size Polyethylene Glycol sodium carboxymethyl cellulose
Consumption 1% 3% 5% 1% 5% 10% 1% 3% 4%
60 ° 45 ° 42 ° 52 ° 40 ° 48 ° 40 ° 38 ° 40 ° of angle of reposes
Hygroscopicity tests 35% 35% 29% 24% 23% 21% 19% 15% 22%
Disintegration 452322001
(not by the screen cloth number)
Tablet lubricants
Pulvis Talci sodium stearate magnesium stearate
Consumption 1% 3% 5% 0.1% 0.5% 1% 0.1% 0.4% 1%
49 ° 43 ° 44 ° 50 ° 41 ° 42 ° 42 ° 36 ° 45 ° of angle of reposes
Hygroscopicity tests 34% 31% 31% 25% 24% 22% 19% 16% 22%
Disintegration 234332001
(not by the screen cloth number)
The pill adjuvant
Pulvis Talci Radix Glycyrrhizae charcoal
Consumption 1% 3% 5% 2% 10% 20%
Hygroscopicity tests 36% 38% 29% 16% 20% 22%
Disintegration 453011
(not by the screen cloth number)
Both can make the problem that ball is smooth, regulate mouthfeel, solution excipient with Radix Glycyrrhizae charcoal coating in the pill preparation, again can Synergistic.
The soft capsule adjuvant
Soybean oil PEG400
Medicated powder: diluent 1: 21: 31: 41: 21: 31: 4
Mobile experiment can carefully can be carefully
Place different time medicine sedimentation situation according to ratio preparation in 1: 3
1 hour 4 hours 8 hours 16 hours standing time
Medicine sedimentation situation does not have sedimentation and does not have the slightly a small amount of sedimentation of sedimentation of sedimentation
Above-mentioned two kinds of adjuvants all can make capsule 's content even, and good fluidity is easy to load, and therefore all can be used as the adjuvant of preparation soft capsule.But the two relatively, and soybean oil requires simple to process conditions, and control easily is less demanding to the capsule softgel shell simultaneously, therefore as first-selected adjuvant.
The drop pill adjuvant
PEG4000?????????????PEG6000
Principal agent: substrate 1: 21: 31: 41: 21: 31: 4
Amalgamation can more carefully can be more carefully
Flowability can be better fine can be better fine
Dissolve scattered time limit 5 4.5 3543
The coolant screening
Kind dimethicone liquid paraffin
Drop pill outward appearance roundness is good, do not have the hangover roundness can, do not have hangover
From coolant, the two can make the drop pill outward appearance all can be up to standard under same condition, but comparatively speaking, dimethicone is a little better.
Pellet
System soft material starch consumption is investigated
Consumption 10% 20% 30%
The pill poor lubricity, extruding is difficult lubricated moderate, and the good lubricity of ball type is big, can't become ball
This shows that 20% starch can increase the lubricity of medicated powder, become the ball effect best.
The gel adjuvant
Kind carbomer carrageenan
Consumption 5% 10% 15% 5% 10% 15%
Good job is slightly carefully slightly carefully for the uniformity
This shows, select not only economy but also can satisfy the requirement of the uniformity of 10% carbomer for use.Therefore, select the pharmaceutical adjunct of 10% carbomer for use as gel.
The specific embodiment:
Embodiments of the invention 1: get Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g, glibenclamide 0.3g
Get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mixes drying thoroughly with concentrated solution, be ground into fine powder, add glibenclamide, 1% sodium carboxymethyl cellulose, granulate, mixing incapsulates, promptly, fill then and make capsule, 3 times on the oral 1st, 1 time 2.
Embodiments of the invention 2: get Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g, glibenclamide 0.3g
Get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae etc. and grinds to form fine powder, mixes drying thoroughly with concentrated solution, be ground into fine powder, add glibenclamide, mixing, make granule, drying adds 0.4% magnesium stearate, tabletting, the bag film-coat promptly, and then is pressed into tablet.
Embodiments of the invention 3: get Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g, glibenclamide 0.3g
Get the decocting that Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine add 6 or 8 times and boiled 1 time 5.5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mix thoroughly with concentrated solution, drying is ground into fine powder, add glibenclamide and 3% sodium carboxymethyl cellulose, mixing is made granule, drying, that is, and then make granule.
Embodiments of the invention 4: get Radix Puerariae 4500g, Radix Rehmanniae 260g, Radix Astragali 100g, Radix Trichosanthis 350g, Stigma Maydis 350g, Fructus Schisandrae Chinensis 100g, Rhizoma Dioscoreae 45g, glibenclamide 0.4g
Get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 or 15 times of decoctings and boiled 1 time 5 hours, also can decoct each 1.5 3 times; Filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mixes thoroughly with concentrated solution, is broken into fine powder, sieves, and pill adds glibenclamide, and with 20% Radix Glycyrrhizae charcoal coating, drying promptly gets pill.
Embodiments of the invention 5: get Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g, glibenclamide 0.3g
With 60% alcohol reflux 3 times, each 2 hours, extracting solution reclaimed ethanol, is condensed into extractum with Radix Puerariae; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part.Reuse 60% ethanol elution chromatographic column flows out to there being saponin, reclaims the concentrated extractum, above-mentioned two extractum mixings made of ethanol, drying is ground into fine powder, adds glibenclamide, add 3 times of medicated powder amount soybean oils (also can use PEG400), the heating mixing incapsulates, promptly.
Embodiments of the invention 6: get Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g, glibenclamide 0.3g
With 60% alcohol reflux 3 times, each 2 hours, extracting solution reclaimed ethanol, is condensed into extractum with Radix Puerariae; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part.Reuse 60% ethanol elution chromatographic column does not flow out to there being saponin, reclaim the concentrated extractum of making of ethanol, above-mentioned two extractum mixings, dry, be ground into fine powder, add glibenclamide, adds 3 times of medicated powder amount PEG6000 mixings (also can use PEG4000), heat and splash in the dimethicone (also can use liquid paraffin) promptly.
Embodiments of the invention 7: get Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g, glibenclamide 0.3g
Getting Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine adds 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma dioscoreae and grinds to form fine powder, mixes thoroughly with concentrated solution, dry, be ground into fine powder, add glibenclamide, add medicated powder weight 20% left and right sides starch mixing, the system soft material, extruding-round as a ball pill promptly.
Embodiments of the invention 8: get Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g, glibenclamide 0.3g
With 60% alcohol reflux 3 times, each 2 hours, extracting solution reclaimed ethanol, is condensed into extractum with Radix Puerariae; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part.Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and recovery ethanol concentrates makes extractum, above-mentioned two extractum mixings, and drying is ground into fine powder, adds glibenclamide, adds 10% carbomer, makes gel.
Embodiments of the invention 9: get Radix Puerariae 300g, Radix Rehmanniae 200g, Radix Astragali 50g, Radix Trichosanthis 300g, Stigma Maydis 300g, Fructus Schisandrae Sphenantherae 50g, Rhizoma Dioscoreae 30g, glibenclamide 0.2g
Get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Sphenantherae, Rhizoma dioscoreae and grinds to form fine powder, mixes drying thoroughly with concentrated solution, be ground into fine powder, add glibenclamide and sieve, mix promptly getting powder.
Embodiments of the invention 10: get Radix Puerariae 5000g, Radix Rehmanniae 300g, Radix Astragali 120g, Radix Trichosanthis 500g, Stigma Maydis 500g, Radix Schisandrae Bicoloris 120g, Rhizoma Dioscoreae 50g, glibenclamide 0.5g
With 60% alcohol reflux 3 times, each 2 hours, extracting solution reclaimed ethanol, is condensed into extractum with Radix Puerariae; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Radix Schisandrae Bicoloris, Rhizoma dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and recovery ethanol concentrates makes extractum, above-mentioned two extractum mixings, and drying is ground into fine powder, adds glibenclamide, adds stevioside and antiseptic again, boils the filtration of dissolving back, adds water and promptly gets syrup.
Claims (15)
1, a kind of preparation for diabetes, it is characterized in that: calculate according to composition by weight, it by: Radix Puerariae 300-5000, Radix Rehmanniae 200-300, Radix Astragali 50-120, Radix Trichosanthis 300-500, Stigma Maydis 300-500, Fructus Schisandrae Chinensis 50-120, Rhizoma Dioscoreae 30-50 and glibenclamide 0.2-0.5 are prepared from.
2, according to the described preparation for diabetes of claim 1, it is characterized in that: it by: Radix Puerariae 4000g, Radix Rehmanniae 240g, Radix Astragali 80g, Radix Trichosanthis 400g, Stigma Maydis 400g, Fructus Schisandrae Chinensis 80g, Rhizoma Dioscoreae 40g and glibenclamide 0.3g add appropriate amount of auxiliary materials and are prepared from.
3, according to claim 1 or 2 described preparation for diabetes, it is characterized in that: described preparation is all preparations that medically allow, and comprising: pill, capsule, soft capsule, tablet, granule, powder, oral liquid, drop pill, pellet or gel.
4, the preparation method of preparation for diabetes as claimed in claim 1 or 2, it is characterized in that: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 6～15 times of decoctings and boil 1～3 time, each 1.5～5.5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mix thoroughly with concentrated solution, drying, medicated powder adds glibenclamide, obtain the material of active ingredient of the present invention, dose different adjuvants then and adopt conventional method to make different preparations.
5, the preparation method of preparation for diabetes as claimed in claim 1 or 2, its feature also is: get Radix Puerariae, with ethanol or water extraction, reclaim solvent, get extracting solution A, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae decoct with water extracting solution B, extracting solution A and B can adopt the method for precipitate with ethanol, column chromatography or supercritical extraction to make with extra care after merging, concentrate, dry, add glibenclamide, obtain containing the material of active ingredient of the present invention, make different preparations with different conventional methods then.
6, according to the preparation method of the described preparation for diabetes of claim 4, it is characterized in that: the capsule in the described preparation prepares like this: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mixes thoroughly with concentrated solution, dry, be ground into fine powder, add glibenclamide, 1% sodium carboxymethyl cellulose, granulate, mixing incapsulates, promptly.
7, according to the preparation method of the described preparation for diabetes of claim 4, it is characterized in that: the tablet in the described preparation prepares like this: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated in right amount, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae etc. and grinds to form fine powder, mixes thoroughly with concentrated solution, drying is ground into fine powder, adds glibenclamide, mixing is made granule, drying, add 0.4% magnesium stearate, tabletting, the bag film-coat, promptly.
8, according to the preparation method of the described preparation for diabetes of claim 4, it is characterized in that: the granule in the described preparation prepares like this: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mixes drying thoroughly with concentrated solution, be ground into fine powder, add glibenclamide and 3% sodium carboxymethyl cellulose, mixing is made granule, drying, promptly.
9, according to the preparation method of the described this preparation for diabetes of claim 4, it is characterized in that: the pill in the described preparation is like this preparation: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mixes thoroughly with concentrated solution, is broken into fine powder, sieve, pill adds glibenclamide, with Radix Glycyrrhizae charcoal coating, drying, promptly.
10, according to the preparation method of the described preparation for diabetes of claim 4, it is characterized in that: the pellet in the described preparation is like this preparation: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mix thoroughly with concentrated solution, drying is ground into fine powder, add glibenclamide, add the starch mixing, the system soft material, extruding-round as a ball pill is promptly.
11, according to the preparation method of the described preparation for diabetes of claim 4, it is characterized in that: the powder in the described preparation is like this preparation: get Radix Puerariae, Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis four Chinese medicine and add 8 times of decoctings and boiled 1 time 5 hours, filter, be concentrated into an amount of, other gets the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae and grinds to form fine powder, mixes thoroughly with concentrated solution, adds glibenclamide, be broken into fine powder, sieve promptly.
12, according to the preparation method of the described preparation for diabetes of claim 5, the soft capsule in the described preparation is like this preparation: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution recovery ethanol was condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and recovery ethanol concentrates makes extractum, above-mentioned two extractum mixings, and drying is ground into fine powder, adds glibenclamide, adds soybean oil, and the heating mixing incapsulates, promptly.
13, according to the preparation method of the described preparation for diabetes of claim 5, it is characterized in that: the drop pill in the described preparation is like this preparation: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution recovery ethanol was condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and reclaim ethanol and concentrate and makes extractum, above-mentioned two extractum mixings, drying is ground into fine powder, adds glibenclamide, adds the PEG6000 mixing, and heating splashes in the dimethicone promptly.
14, according to the preparation method of the described preparation for diabetes of claim 5, it is characterized in that: the gel in the described preparation is like this preparation: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution recovery ethanol was condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and recovery ethanol concentrates makes extractum, above-mentioned two extractum mixings, and drying is ground into fine powder, adds glibenclamide, adds carbomer, makes gel.
15, according to the preparation method of the described preparation for diabetes of claim 5, it is characterized in that: the oral liquid in the described preparation is like this preparation: get Radix Puerariae with 60% alcohol reflux 3 times, each 2 hours, extracting solution recovery ethanol was condensed into extractum; Radix Rehmanniae, Stigma Maydis, Radix Trichosanthis, the Radix Astragali, Fructus Schisandrae Chinensis, Rhizoma Dioscoreae add 10 times of decoctings and boil 2 times, each 2 hours, decoction liquor is crossed macroporous resin column, being washed to sugar-free flows out, adding ethanol after effluent concentrates makes and contains the alcohol amount and reach 80% and precipitate, precipitation adds 10 times of dissolved in distilled water to be crossed hollow fiber column and carries out molecular retention, keeps molecular weight in 5000～40000 part; Reuse 60% ethanol elution chromatographic column flows out to there being saponin, and recovery ethanol concentrates makes extractum, above-mentioned two extractum mixings, and drying is ground into fine powder, adds glibenclamide, adds stevioside and antiseptic again, boils the filtration of dissolving back, adds water promptly.
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| CNB2005100546952A CN100482267C (en) | 2004-03-17 | 2005-03-16 | Preparation for diabetes and its making method |
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| CN 200410022076 CN1562188A (en) | 2004-03-17 | 2004-03-17 | Wasting-thirst preparaton and preparation method |
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| CNB2005100546952A CN100482267C (en) | 2004-03-17 | 2005-03-16 | Preparation for diabetes and its making method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101934036A (en) * | 2010-08-26 | 2011-01-05 | 广州中一药业有限公司 | Method for preparing medicament for treating diabetes mellitus |
| CN110354202A (en) * | 2019-07-30 | 2019-10-22 | 吉林农业科技学院 | The preparation process of glutinous rehmannia Xiaoke Tablets |
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2005
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101934036A (en) * | 2010-08-26 | 2011-01-05 | 广州中一药业有限公司 | Method for preparing medicament for treating diabetes mellitus |
| CN101934036B (en) * | 2010-08-26 | 2013-04-24 | 广州白云山中一药业有限公司 | Method for preparing medicament for treating diabetes mellitus |
| CN110354202A (en) * | 2019-07-30 | 2019-10-22 | 吉林农业科技学院 | The preparation process of glutinous rehmannia Xiaoke Tablets |
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