CN101108207A - Antidiabetic pharmaceutical composition and method of preparing the same - Google Patents
Antidiabetic pharmaceutical composition and method of preparing the same Download PDFInfo
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- CN101108207A CN101108207A CNA2006100990505A CN200610099050A CN101108207A CN 101108207 A CN101108207 A CN 101108207A CN A2006100990505 A CNA2006100990505 A CN A2006100990505A CN 200610099050 A CN200610099050 A CN 200610099050A CN 101108207 A CN101108207 A CN 101108207A
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Abstract
The invention discloses a medicine assembly for curing Antidiabetics and also the preparation method. The detained procedures of the medicine assembly are that: respectively extract and purify the cortex mori radicis and kudzu root, condense the eluent of the two respectively and then spraying dry or pressure reduction dry the condensed eluent after mixed in certain proportion; also can separately dry the two eluent to achieve the extraction of the cortex mori radicis and kudzu root and then mix them according to certain proportion. The invention can be used for preparing medicines for curing hyperglycemia, diabetes and other complicating diseases.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and its production and use, particularly a kind of hypoglycemic pharmaceutical composition and preparation method thereof.
Background technology
" diabetic medicine " Diabate Medicine, 10, the report alpha-glucosidase inhibitor has suppressed to be present in the alpha-glucosidase of intestinal microvillus in 688 (1993), thereby thereby disturbs the rapid digestion of carbohydrate in the diet and absorption to reach the purpose that reduces the insulin requirement amount.There are some potential advantages in this Therapeutic Method, and comprising not can weight increase, in some cases even can reduce body weight, does not have hyperinsulinemia simultaneously, and when treating separately, does not have hypoglycemic danger.Acarbose (Acarbose) be first by the alpha-glucosidase inhibitor of clinical practice, the intestinal brush border alpha-glucosidase inhibitor of recent findings comprises miglitol (miglitol), voglibose (voglibose), emiglitate etc.For the traditional Chinese medicine of China, still rare aspect the research and development of alpha-glucosidase inhibitor.
Cortex Mori (CORTEX MORI) is the dry root bark of moraceae plants Mulberry Morus alba L., is a kind of conventional Chinese medicine, and the effect eliminating pathogen from the lung for relieving asthma cures mainly dyspnea and cough due to lung-heat, diseases caused by retention of fluid stops lung, edema, dysuria.On the books in ancient times with Cortex Mori treatment diabetes: as Radix Mori soup (" a thousand pieces of gold wing " volume 19).Modern medicine study shows that Cortex Mori has hypoglycemic effect and has inhibitory action relevant with it to alpha-glucosidase.Radix Puerariae (RADIX PUERARIAE) is the dry root of the perennial liana bavin of pulse family Pueraria lobota Pueraria lobata (Willd) Ohwi, is the tcm clinical practice common drug, and the Radix Puerariae beginning is stated from Shennong's Herbal, classifies middle product as.The successive dynasties book on Chinese herbal medicine is all on the books.Its single medicinal material or compound recipe are widely used in the treatment of diabetes.Though Cortex Mori and Radix Puerariae use as antidiabetic drug, have not yet to see the report of Cortex Mori and Radix Puerariae combined therapy diabetes in the Chinese medicine prescription.
Summary of the invention
The object of the present invention is to provide a kind of pharmaceutical composition; Second purpose of the present invention is to provide a kind of hypoglycemic pharmaceutical composition; The 3rd purpose of the present invention is to provide this preparation of drug combination method.
The present invention seeks to be achieved through the following technical solutions:
The raw material medicaments in part by weight of pharmaceutical composition of the present invention consists of: Cortex Mori: Radix Puerariae is 1～6: 1; Preferred Cortex Mori: Radix Puerariae is 5: 1; Cortex Mori: Radix Puerariae is 4: 1; Cortex Mori: Radix Puerariae is 3: 1.
Preparation of drug combination method of the present invention is:
The Cortex Mori medical material is used water extraction through after cutting or pulverizing, and the extraction temperature is room temperature～90 ℃, and the total solvent amount is 14～30 times of weight portions of medical material, and extraction time is 2～4 times, each 1～5 hour; Three extracting solution are merged; 50～75 ℃ of concentrating under reduced pressure, with the centrifugal carbon column of going up of the concentrated solution of 1～5 times of medical material weight portion, used activated carbon is 0.5～3 times of medical material weight portion, can select powder-type or granular pattern for use, spend the night with distilled water immersion before using, wet method dress post, upper prop liquid temp are room temperature～75 ℃, extracting solution also can through behind the further precipitate with ethanol with the formal carbon column of aqueous solution; (this moment, ninhydrin reaction was negative) used 10～50% ethanol elution instead when water was eluted to the water lotion clarification after upper prop finished, with 1-naphthols reagent qualitative detection total sugar, when the Molish loss for reaction, finish eluting, 50～90 ℃ are concentrated into 30 ℃ of density with ethanol elution and are about 1.20～1.25, or the volume of concentrated solution is 0.05～0.1 times of weight portion of medical material, the Cortex Mori concentrated solution is stand-by;
The Radix Puerariae medical material is used water extraction through after cutting or pulverizing, and extracting temperature is 50～100 ℃, and the total solvent amount is 15～30 times of weight portions of medical material, and extraction time is 2～4 times, each 1～3 hour; Three extracting solution are merged; 50～90 ℃ of normal pressures or concentrating under reduced pressure, the concentrated solution of 2～5 times of medical material weight portions is centrifugal, macroporous resin column on the supernatant, upper prop finish the back water when being eluted to no total sugar total sugar reaction Molish react negative, use 30%～90% ethanol elution instead, finish eluting when being negative with ferric chloride reagent qualitative detection flavone, 50～90 ℃ of following alcohol eluens are concentrated into 30 ℃ of density and are about 1.31～1.35, or the volume of concentrated solution is 0.1～0.3 times of weight portion of medical material, the Radix Puerariae concentrated solution is stand-by; Behind above-mentioned Cortex Mori concentrated solution and the Radix Puerariae concentrated solution mix homogeneously 50～70 ℃ of normal pressures, drying under reduced pressure or carry out spray drying after, promptly get Cortex Mori and Radix Puerariae mixed extract, be called for short the Mulberry pueraria root extract;
Cortex Mori concentrated solution and Radix Puerariae concentrated solution also can be distinguished after routinely normal pressure, decompression or the spray drying to such an extent that Cortex Mori extract and Radix Puerariae extract remix are even, the Mulberry pueraria root extract;
The Mulberry pueraria root extract is added conventional excipients,, make clinical acceptable forms, include but not limited to concentrated pill, capsule, drop pill, granule, tablet, soft capsule, slow releasing agent, oral liquid or lyophilized injectable powder according to common process.
Said method the 1-deoxynojirimycin in the handy high effective liquid chromatography for measuring Mulberry pueraria root extract be that the content of DNJ is 15～60mg/g, puerarin content is 50～160mg/g.
Preparation of drug combination method of the present invention is preferably:
The Cortex Mori medical material use water extraction through after cutting or pulverizing, and the extraction temperature is 50 ℃, and the total solvent amount is 17 weight portions of medical material, and extraction time is 3 times, and the time is (2+1+1) hour; Three extracting solution are merged; 60～65 concentrating under reduced pressure, with the centrifugal carbon column of going up of the concentrated solution of 3 times of medical material weight portions, used activated carbon is 1 times of medical material weight portion, granular pattern, spend the night with distilled water immersion before using, wet method dress post, the upper prop liquid temp is 50 ℃, extracting solution also can through behind the further precipitate with ethanol with the formal carbon column of aqueous solution; (this moment, ninhydrin reaction was negative) used 15% ethanol elution instead when water was eluted to the water lotion clarification after upper prop finished, finish eluting when the Molish loss for reaction with 1-naphthols reagent qualitative detection total sugar, 60 ℃～65 ℃ concentrated with ethanol elution, concentrated solution is concentrated into 30 ℃ of density and is about 1.20～1.25, or the volume of concentrated solution is 0.05～0.1 times of weight portion of medical material, the Cortex Mori concentrated solution is stand-by;
The Radix Puerariae medical material is used water extraction through after cutting or pulverizing, and extracting temperature is 50 ℃ of room temperatures, and the total solvent amount is 22 times of weight portions of medical material, and extraction time is 3 times, each 2 hours; Extracting solution is merged; 75 ℃ of extracting solution concentrating under reduced pressure, centrifugal, with macroporous resin column on the supernatant of 3 times of medical material weight portions, upper prop finish the back water when being eluted to no total sugar Molish react negative, use 75% ethanol elution instead, finish eluting when being negative reaction with ferric chloride reagent qualitative detection flavone, 50～90 ℃ of following alcohol eluens are concentrated into 30 ℃ of density and are about 1.31～1.35, or the volume of concentrated solution is 0.1～0.3 times of weight portion of medical material, the Radix Puerariae concentrated solution is stand-by;
Above-mentioned Cortex Mori concentrated solution and Radix Puerariae concentrated solution are in the ratio of crude drug, i.e. Cortex Mori: Radix Puerariae is evenly 60～65 ℃ of drying under reduced pressure in back of 5: 1 mixed, promptly gets the Mulberry pueraria root extract; After Cortex Mori concentrated solution and Radix Puerariae concentrated solution also can be pressed normal pressure, decompression or spray drying respectively, the mixed of pressing crude drug again, i.e. Cortex Mori medical material: the Radix Puerariae medical material was that 5: 1 mixed are even, got the Mulberry pueraria root extract.
The Mulberry pueraria root extract is added conventional excipients,, make clinical acceptable concentrated pill, capsule, drop pill, granule, tablet, soft capsule, slow releasing agent, oral liquid or lyophilized injectable powder according to common process.
Water in the said extracted solvent can also substitute the concentration of alcoholic solution preferred 10%～90% with alcoholic solution;
The said extracted method can be that conventional the stirring extracted, soaked and extract or heating and refluxing extraction;
Above-mentioned macroporous resin is selected styrene type low pole or non-polar macroporous resin for use, the resin of preferred DS401, AB-8, NKA, D4006, DA201 or DB-301 model.
Pharmaceutical composition of the present invention can be used for preparing the medicine for the treatment of hyperglycemia, diabetes and complication thereof.
Pharmaceutical composition of the present invention is through clinical research confirmation: alkaloidss such as the 1-deoxynojirimycin that Cortex Mori contains (being called for short DNJ), N-Me-DNJ, GAL-DNJ, fagomine are the clear and definite alpha-glucosidase inhibitor of effect, and DNJ has very strong alpha-glucosaccharase enzyme inhibition; Results of in vitro studies shows that DNJ is to the inhibitory action difference of alpha-glucosidase in the different animals body, and it suppresses the IC of saccharase and maltase
50Scope is respectively 6.6～16 * 10
-8M and 7.4～63 * 10
-8M, DNJ shows as competitive inhibition to alpha-glucosidase, often acts near substrate binding site or its; But Radix Puerariae decoct blood sugar lowering, puerarin (one of main active of Radix Puerariae) can significantly reduce the blood glucose of alloxan induced hyperglycemia mice, obviously improve the carbohydrate tolerance of alloxan mice, to adrenolytic blood glucose increasing effect, puerarin also has therapeutical effect to diabetic complication, comprises diabetic peripheral neuropathy, diabetic nephropathy and diabetic renal papillary necrosis etc.The present invention utilizes modern separation and purification means to remove the impurity component in the two flavor medicines and has improved content of effective in the extract, it is big to have overcome traditional prescription dose, take inconvenient shortcoming, be used for the treatment of hyperglycemia, diabetes and complication thereof and have better therapeutic.
Following experiment and embodiment are used to further specify but are not limited to the present invention.
Experimental example 1 usefulness pig intestinal mucosa glucosidase suppress model relatively Mulberry pueraria root extract and Cortex Mori extract, Radix Puerariae extract to the inhibitory action of glucosidase.
(1) pig intestinal mucosa glucosidase: derive from pig small intestine jejunal segment brush border.Preparation process is: gets the fresh pig small intestinal, cleans up, scrape and get small intestinal mucosa, and homogenized, 4 ℃ of placements are spent the night, centrifugal 2 times, merge supernatant, sulfur ammonium precipitation, placement is spent the night, high speed frozen centrifugation 2 times, the collecting precipitation and the desalination of dialysing, the thick enzyme lyophilization of gained obtains the faint yellow solid powder.Be mixed with 10mg/ml solution with phosphate buffer during use.
(2) medicine and reagent
0.05M phosphate buffer; Maltose: Shanghai chemical reagents corporation, lot number F20030512 is mixed with the solution of 56mM; Glucose kit (external diagnosis reagent case): Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd., lot number 240811.
(3) experimental apparatus
Thermostat water bath, Tianjin, island UV-1601PV type spectrophotometer.
(4) when the medical material total amount is consistent, Cortex Mori extract, Radix Puerariae extract and Mulberry pueraria root extract all are mixed with the concentration of 0.4g crude drug/ml, and dilute in proportion, draw suppression ratio-concentration curve.
(5) experimental technique
The collection of the carrying out of A, enzymatic reaction and sample: get pig small intestine mucosa glucoside enzymatic solution 0.1ml and add in the test tube, add glucosidase inhibitor 0.1ml more respectively, add substrate maltose solution 0.2ml, 37 ℃ of isothermal reactions 45 minutes.Again above test tube is heated 8 minutes cessation reactions in boiling water bath, then in test tube, add the 0.6ml distilled water, left standstill 5 minutes, get supernatant and measure glucose content.
Determination of glucose and evaluation of result in B, the sample: determination of glucose adopts the liquid of glucose test kit in the sample, test kit R1 and R2 liquid are pressed 1: 9 mixed, in test tube, add the 1.5ml mixed liquor earlier, add sample 30 μ l again, 37 ℃ of reaction 15min.Colorimetry 510nm measures light absorption value; Under the condition that the alpha-glucosidase inhibitor of variable concentrations exists, the release of glucose during with the unrestraint agent percentage ratio of glucose represent.To suppress percentage rate different inhibitor concentration are mapped, get dose-effect curve, and make fit equation, calculate the IC of every curve
50Value, result such as table 1:
Table 1 Cortex Mori Radix Puerariae different proportion sample is to the inhibition activity of thick enzyme
| Sample | Cortex Mori Radix Puerariae medical material proportioning | Matched curve and IC 50Value |
| Cortex Mori extract Radix Puerariae extract Cortex Mori Radix Puerariae extract | 1∶1 3∶1 5∶1 | y＝9.4438Ln(x)+62.232 IC 50＝0.274mg/ml y＝4.537Ln(x)+53.11 IC 50＝0.504mg/ml y＝14.309Ln(x)+69.92 IC 50＝0.249mg/ml y＝17.643Ln(x)+81.79IC 50＝0.165mg/ml y＝20.137Ln(x)+105.80IC 50＝0.063mg/ml |
Use the pig intestinal mucosa glucosidase and suppress the experiment of model determination vitro inhibition glucosidase activity, the result shows: Cortex Mori extract and Radix Puerariae extract all have a glucoside enzyme inhibition external, and the two makes up this inhibitory action in back according to a certain ratio tangible enhancing.
Experimental example 2 usefulness counter-rotating intestinal capsule technology assessment Mulberry pueraria root extract is to the alpha-glucosidase inhibitor inhibitory action
Experiment material:
(1). principle: counter-rotating intestinal capsule technology can be used for studying intestinal enzymes effect to substrate in the incubation bottle.The experiment purpose of this research is earlier counter-rotating intestinal capsule technology to be carried out methodological study, by the method DNJ and the alpha-glucosaccharase enzyme inhibition that tried Cortex Mori Radix Puerariae extract medicine is estimated then.
(2). laboratory animal: the Wistar rat, ♂, 120-140g, available from Beijing Vital River Experimental Animals Technology Co., Ltd., licence numbering: SCXK (capital) 2002-2003.
(3). experimental drug and reagent
Cortex Mori Radix Puerariae extract: the sample that derives from embodiment 4; Amylase: the Sigma product, 100mg/ props up, 1070U/mg.Use dissolved in distilled water during use, make 4000U/g starch (get the 22.4mg α-Dian Fenmei, be dissolved in the 1ml distilled water, get 10 μ l/6ml starch solutions); Krebs-Henseleit buffer: NaHCO
325.0mM, NaCl 118mM, KCl 4.7mM, MgSO
41.2mM, NaH
2PO
41.2mM, CaCl
21.2mM.Elder generation is with NaHCO during preparation
3, NaCl, KCl, NaH
2PO
4Dissolving adds MgSO at last again
4And CaCl
2Soluble starch: martial music chemical plant, Pengzhou City, Sichuan Province, lot number: 20010108.Be mixed with 1% suspension during use with the Krebs-Henseleit buffer, in tool plug triangular flask, insert then in the water-bath about 95 ℃ and heat 13min, during constantly be mixed.
Experimental technique:
(1) preparation of substrate and administration: after 1% starch solution heating for dissolving, add α-Dian Fenmei by a certain percentage, be mixed, react 10min in 37 ℃ of water-baths, reaction finishes the back does not have chromogenic reaction with iodine liquid, illustrates that starch has been broken down into oligosaccharide fully.Add this solution 6ml in the triangular flask of each 25ml, what add each concentration again is subjected to the reagent thing standby.
(2) preparation of intestinal capsule: the sacrificed by decapitation male rat, cut and take out small intestinal in the duodenum upper end.By stainless pin small intestinal is reversed, be cut into the segment of 7-8cm, the end surgical thread ligation of every section small intestinal, the preparation of this section intestinal capsule has been finished in ligation after the other end pours into small intestinal with 1ml Krebs-Henseleit buffer.Place freezing Krebs-Henseleit buffer standby in each intestinal capsule.
(3) collection of the carrying out of enzymatic reaction and sample: in advance shaking table is preheating to 37 ℃ standby.Treat that all intestinal capsule preparations finish, they be added in each triangular flask at random that with 37 ℃ temperature, 30 rev/mins rotating speed reacts on shaking table.Take out each triangular flask behind the 2h, every bottle adds 10 μ l 1mol/L HCl cessation reactions.Take out the intestinal capsule then from triangular flask, cut the intestinal capsule and make interior liquid of intestinal capsule and the liquid mixing in the triangular flask, sample 0.5ml is collected in the back that is mixed, and 4 ℃ of refrigerators are preserved.
(4) determination of glucose and evaluation of result in the sample: under the condition that the alpha-glucosidase inhibitor of variable concentrations exists, the release of glucose during with the unrestraint agent percentage ratio of glucose represent.To suppress percentage rate different inhibitor concentration are mapped, get dose-effect curve.The results are shown in Table 2.
Table 2 inhibitory action of counter-rotating intestinal capsule technology assessment Mulberry pueraria root extract to glucosidase
| The experiment medicine | Be subjected to reagent thing final concentration (μ g/ml) | Suppression ratio (%) | Matched curve |
| The Cortex Mori Radix Puerariae extract | 4.28 12.83 38.52 115.70 346.70 | 4.05 38.86 51.89 74.58 91.65 | y＝19.195Ln(x)-17.879 Ic 50＝34.329μg/ml |
From the The above results analysis as can be known, the Cortex Mori Radix Puerariae extract is stronger to the inhibitory action of glucosidase.
Experimental example 3 Mulberry pueraria root extract single-doses are to the influence of the oral starch tolerance experiment of normal rat
Laboratory animal is selected the Wistar rat about 180g for use, and ♂ is divided into matched group and administration group, that the administration group is divided into again is little, in, big three dosage groups, 15 every group.After one night of fasting, cut tail and get blood, measure blood glucose immediately, as fasting glucose, that administration group subsequently gives is little, in, heavy dose of Cortex Mori Radix Puerariae extract, and giving the starch solution of 2g/kg simultaneously, matched group then gives the distilled water and the starch solution of same volume, cuts tail later on successively and measure blood glucose when 30min, 60min, 120min.Experimental result sees Table 3.
Table 3 Cortex Mori Radix Puerariae extract is to the influence of normal rat starch tolerance test
| Group | Dosage (g/kg) | Blood glucose (mmol/l) | |||
| 0min | 30min | 60min | 120min | ||
| Matched group administration group | - 111.2 222.4 444.8 | 4.33±0.50 4.46±0.84 4.61±0.78 4.19±0.85 | 15.84±3.47 11.16±2.23** 8.29±1.62** 6.01±0.97** | 12.31±1.74 10.78±1.57 9.75±2.01 6.51±0.94** | 7.09±1.07 7.14±1.48 7.04±1.22 6.89±1.12 |
N=15 is compared with matched group in * p＜0.01
Glycemic peaks appears from above interpretation of result control rats giving starch solution 30min, and administration group glycemic peaks after giving starch becomes very mild, in the administration group little, in, in big three dosage groups tangible dose-effect relationship is arranged, illustrate that the present invention extracts the Cortex Mori Radix Puerariae extract intestinal alpha-glucosidase enzyme of normal rat is had significant inhibitory effect.
Description of drawings
Fig. 1: with the inhibitory action of counter-rotating intestinal capsule technology assessment Cortex Mori Radix Puerariae extract to glucosidase
Fig. 2: Cortex Mori Radix Puerariae extract single-dose is to the influence of normal rat starch tolerance test
Following embodiment all can realize the effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1:
1000g Cortex Mori medical material is through after the cutting, 35 ℃ are stirred extraction three times, amount of water be medical material weight (8+6+6) doubly, extraction time is (2+1+1) hour, three times extracting solution merges, 60 ℃ of concentrating under reduced pressure, the centrifugal carbon column (the activated carbon model is GH-15, consumption 1000g, wet method dress post) of going up of concentrated solution 2000ml, complete back water eluting on the sample, (this moment, ninhydrin reaction was negative) uses 15% ethanol elution instead when water lotion is clarified, and with 1-naphthols reagent qualitative detection total sugar, finishes eluting when the Molish loss for reaction, 60～65 ℃ of concentrating under reduced pressure of 15% ethanol elution, it is stand-by that alcohol eluen is concentrated into the 50ml left and right sides;
The Radix Puerariae medical material of 166 grams is through after the cutting, 60 ℃ of heated and stirred of water are extracted three times, amount of water be medical material weight (9+6+5) doubly, extraction time is (2+1+1) hour, three times extracting solution merges, 60 ℃ of concentrating under reduced pressure, centrifugal, supernatant 600ml goes up the NKA macroporous resin column, water eluting always behind the intact post on the sample, to water lotion clarification (total sugar reaction this moment Molish reaction is negative), use 50% ethanol elution instead, with ferric chloride reagent qualitative detection flavone, finish during loss for reaction to collect, it is stand-by that alcohol eluen is concentrated into 20ml;
65～75 ℃ of ℃ of drying under reduced pressure behind above-mentioned Cortex Mori concentrated solution and the Radix Puerariae concentrated solution mix homogeneously obtain Mulberry pueraria root extract 58 grams; The DNJ content of measuring in the extract with high performance liquid chromatography (HPLC) is 45mg/g, and puerarin content is 120mg/g;
Above Mulberry pueraria root extract adds adjuvant, through conventional technology; Make slow releasing preparation.
Embodiment 2:
1000 gram Cortex Mori medical materials are through after the cutting, 50 ℃ are stirred the extraction secondary, amount of water be medical material weight (10+8) doubly, extraction time is (2+1) hour, secondary raffinate merges, 60 ℃ of concentrating under reduced pressure, (the activated carbon model is GH-1 to the centrifugal upward carbon column of concentrated solution 3000ml, consumption 500 gram, wet method dress post), intact back water is eluted to when water lotion clarify (ninhydrin reaction is negative at this moment) and uses 25% ethanol elution instead on the sample, with 1-naphthols reagent qualitative detection total sugar, finish eluting when the Molish loss for reaction, 60～65 ℃ of concentrating under reduced pressure dryings of 25% ethanol elution get Cortex Mori extract; The Radix Puerariae medical material of 250 grams extracts twice through 90 ℃ of heated and stirred of water after the cutting, amount of water be medical material weight (10+8) doubly, extraction time is (2+1) hour, extracted twice liquid merges, 60～65 ℃ of concentrating under reduced pressure, centrifugal, supernatant 750ml goes up the AB-8 macroporous resin column, when water is eluted to no total sugar always behind the intact post on the sample (total sugar reaction Molish reacts negative), use 60% ethanol elution instead, finish during with ferric chloride reagent qualitative detection flavone → loss for reaction to collect, alcohol eluen concentrates, and obtains Radix Puerariae extract;
70～75 ℃ of drying under reduced pressure behind above-mentioned Cortex Mori extract and the Radix Puerariae extract mix homogeneously promptly get Mulberry pueraria root extract 50 grams, and the DNJ content of measuring in the extract with HPLC is 35mg/g, and puerarin content is 90mg/g;
Above Mulberry pueraria root extract adds conventional adjuvant, through conventional technology; Make concentrated pill.
Embodiment 3:
1000 gram Cortex Mori medical materials are through after the cutting, alcohol heating reflux with 30% extracts three times, quantity of solvent be medical material weight (7+5+5) doubly, extraction time is (2+1+1) hour, three times extracting solution merges, 60 ℃ of concentrating under reduced pressure, fling to ethanol and be concentrated into that 4000ml is centrifugal to be gone up carbon column (the activated carbon model is GH-1, consumption 1000 grams, wet method dress post), (this moment, ninhydrin reaction was negative) used 30% ethanol elution instead when the back water was eluted to the water lotion clarification fully on the sample, with 1-naphthols reagent qualitative detection total sugar, when the Molish loss for reaction, finish eluting, 60 ℃ of concentrating under reduced pressure of 30% ethanol elution, concentrated solution is stand-by;
The Radix Puerariae medical material of 330 grams is through extracting twice with 80% alcohol heating reflux after the cutting, alcohol adding amount be medical material weight (10+8) doubly, extraction time is (2+1) hour, extracted twice liquid merges, 60 ℃ of concentrating under reduced pressure are flung to ethanol and are changed into aqueous solution, centrifugal back supernatant 1000ml goes up the DS-401 macroporous resin column, when water is eluted to the water lotion clarification always behind the intact post on the sample, use 75% ethanol elution instead, with ferric chloride reagent qualitative detection flavone, finish during loss for reaction to collect, alcohol eluen concentrates, and obtains Radix Puerariae extract;
55 ℃ of drying under reduced pressure behind above-mentioned Cortex Mori extract and the Radix Puerariae extract mix homogeneously promptly get Mulberry pueraria root extract 40 grams, and the DNJ content of measuring in the extract with HPLC is 20mg/g, and puerarin content is 140mg/g;
Above Mulberry pueraria root extract adds conventional adjuvant, through conventional technology; Make oral liquid.
Embodiment 4:
10KG Cortex Mori medical material is through after the cutting, 50 ℃ are stirred extraction three times, amount of water be medical material weight (8+6+6) doubly, extraction time is (2+1+1) hour, three times extracting solution merges, 60 ℃ of concentrating under reduced pressure, the centrifugal carbon column (the activated carbon model is GH-15, consumption 12KG, wet method dress post) of going up of concentrated solution 25L, complete back water eluting on the sample, use 15% ethanol elution instead until water lotion clarification (this moment, ninhydrin reaction was negative),, finish eluting during loss for reaction with 1-naphthols reagent qualitative detection total sugar, 70 ℃ of concentrating under reduced pressure of 15% ethanol elution, concentrated solution is stand-by;
The Radix Puerariae medical material of 2KG extracts three times through 60 ℃ of heated and stirred of water after the cutting, amount of water be medical material weight (9+6+5) doubly, extraction time be (2+1+1) hour, three extracting solution merging, 70 ℃ of concentrating under reduced pressure, centrifugal, DS40 macroporous resin column on the supernatant when water is eluted to the water lotion clarification always behind the intact post on the sample (the Molish reaction is negative), is used 85% ethanol elution instead, with ferric chloride reagent qualitative detection flavone, finish during loss for reaction to collect, alcohol eluen concentrates, and is stand-by;
Spray drying behind above-mentioned Cortex Mori concentrated solution and the Radix Puerariae concentrated solution mix homogeneously obtains Mulberry pueraria root extract 456 grams, and the DNJ content of measuring in the extract with high performance liquid chromatography (HPLC) is 34mg/g, and puerarin content is 80mg/g;
Above Mulberry pueraria root extract adds conventional adjuvant, through conventional technology; Make tablet.
Embodiment 5:
1000 gram Cortex Mori medical materials are through after the cutting, 50 ℃ are stirred extraction three times, amount of water be medical material weight (8+6+6) doubly, extraction time is (2+1+1) hour, three times extracting solution merges, 60 ℃ are evaporated to 3000ml, add 95% ethanol 9000ml precipitate with ethanol, placement is spent the night, and is centrifugal, and supernatant concentration is flung to ethanol and added water and is settled to 3000ml and goes up carbon column (the activated carbon model is GH-1, consumption 1000 grams, wet method dress post), (this moment, ninhydrin reaction was negative) used 30% ethanol elution instead when the back water was eluted to the water lotion clarification fully on the sample, with 1-naphthols reagent qualitative detection total sugar, when the Molish loss for reaction, finish eluting, 60 ℃ of concentrating under reduced pressure of 30% ethanol elution, the concentrated solution drying under reduced pressure obtains dry clean cream 30 grams of Cortex Mori extract;
The Radix Puerariae medical material of 1000 grams is through extracting twice with 80% alcohol heating reflux after the cutting, alcohol adding amount be medical material weight (10+8) doubly, extraction time is (2+1) hour, extracted twice liquid merges, 60 ℃ of concentrating under reduced pressure are flung to ethanol and are changed into aqueous solution, centrifugal back supernatant 80ml goes up the DS-401 macroporous resin column, water eluting always behind the intact post on the sample, (the Molish reaction is negative) uses 90% ethanol elution instead during the water lotion clarification, with ferric chloride reagent qualitative detection flavone, finish during loss for reaction to collect, alcohol eluen concentrates, and obtains Radix Puerariae extracting solution, the concentrated solution drying under reduced pressure obtains dry clean cream 70 grams of Radix Puerariae extract;
Behind the dry clean cream mix homogeneously of above-mentioned Cortex Mori extract and Radix Puerariae extract, obtain the Mulberry pueraria root extract, the DNJ content of measuring in the extract with HPLC is 15mg/g, and puerarin content is 150mg/g; Above Mulberry pueraria root extract adds conventional adjuvant, through conventional technology; Make granule.
Embodiment 6:
Get Cortex Mori 60kg: Radix Puerariae 10kg extracts routinely, preparation technology makes capsule.
Embodiment 7:
Get Cortex Mori 50kg: Radix Puerariae 10kg extracts routinely, preparation technology makes tablet.
Embodiment 8:
Get Cortex Mori 10kg: Radix Puerariae 10kg extracts routinely, preparation technology makes granule.
Claims (10)
1. hypoglycemic pharmaceutical composition, it is characterized in that the raw material medicaments in part by weight of this pharmaceutical composition consists of: Cortex Mori: Radix Puerariae is 1～6: 1.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material medicaments in part by weight of this pharmaceutical composition consists of: Cortex Mori: Radix Puerariae is 5: 1.
3. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material medicaments in part by weight of this pharmaceutical composition consists of: Cortex Mori: Radix Puerariae is 4: 1.
4. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material medicaments in part by weight of this pharmaceutical composition consists of: Cortex Mori: Radix Puerariae is 3: 1.
5. as the arbitrary described preparation of drug combination method of claim 1～4, it is characterized in that this method is: the Cortex Mori medical material is through after cutting or pulverizing, use water extraction, the extraction temperature is room temperature～90 ℃, the total solvent amount is 14～30 times of weight portions of medical material, extraction time is 2: 4 times, each 1～5 hour; Three extracting solution are merged; 50～75 ℃ of concentrating under reduced pressure, with the centrifugal carbon column of going up of the concentrated solution of 1～5 times of medical material weight portion, used activated carbon is 0.5～3 times of medical material weight portion, can select powder-type or granular pattern for use, spend the night with distilled water immersion before using, wet method dress post, upper prop liquid temp are room temperature～70 ℃, extracting solution also can through behind the further precipitate with ethanol with the formal carbon column of aqueous solution; When water was eluted to the water lotion clarification after upper prop finished, this moment, ninhydrin reaction was negative; Use 10～50% ethanol elution instead, with 1-naphthols reagent qualitative detection total sugar, when the Molish loss for reaction, finish eluting, 50～90 ℃ are concentrated into 30 ℃ of density with ethanol elution and are about 1.20～1.25, or the volume of concentrated solution is 0.05～0.1 times of weight portion of medical material, the Cortex Mori concentrated solution is stand-by;
The Radix Puerariae medical material is used water extraction through after cutting or pulverizing, and extracting temperature is 50～100 ℃, and the total solvent amount is 15～30 times of weight portions of medical material, and extraction time is 2～4 times, each 1～3 hour; Three extracting solution are merged; 50～90 ℃ of following normal pressures or concentrating under reduced pressure, the concentrated solution of 2～5 times of medical material weight portions is centrifugal, macroporous resin column on the supernatant, upper prop finish the back water when being eluted to no total sugar Molish react negative, use 30%～90% ethanol elution instead and begin to receive eluent, finish eluting when being negative with ferric chloride reagent qualitative detection flavone, 50～90 ℃ of following alcohol eluens are concentrated into 30 ℃ of density and are about 1.31～1.35, or the volume that is concentrated into concentrated solution is 0.1～0.3 times of weight portion of medical material, the Radix Puerariae concentrated solution is stand-by;
After 50～90 ℃ of normal pressures, drying under reduced pressure or spray dryinges, promptly get Cortex Mori and Radix Puerariae mixed extract behind Cortex Mori concentrated solution and the Radix Puerariae concentrated solution mix homogeneously, be called for short the Mulberry pueraria root extract; Or after Cortex Mori concentrated solution and Radix Puerariae concentrated solution pressed normal pressure, decompression or spray drying respectively, mix homogeneously, the Mulberry pueraria root extract;
The Mulberry pueraria root extract is added conventional excipients,, make concentrated pill, capsule, drop pill, granule, tablet, soft capsule, slow releasing agent or the oral liquid of clinical acceptance according to common process.
6. preparation of drug combination method as claimed in claim 5 is characterized in that this method is:
The Cortex Mori medical material is used water extraction through after cutting or pulverizing, and extracting temperature is 50 ℃, and the total solvent amount is medical material 17 weight portions, and extraction time is 3 times, and the time of at every turn mentioning is 2 hours, 1 hour, 1 hour; Three extracting solution are merged; 60 ℃～65 ℃ concentrating under reduced pressure, with the centrifugal carbon column of going up of the concentrated solution of 3 times of medical material weight portions, used activated carbon is 1 times of medical material weight portion, granular pattern, spend the night with distilled water immersion before using, wet method dress post, the upper prop liquid temp is 50 ℃, extracting solution also can through behind the further precipitate with ethanol with the formal carbon column of aqueous solution; When water was eluted to the water lotion clarification after upper prop finished, this moment, ninhydrin reaction was negative; Use 15% ethanol elution instead, with 1-naphthols reagent qualitative detection total sugar, when the Molish loss for reaction, finish eluting, 60 ℃～65 ℃ concentrated with ethanol elution, it is 1.20～1.25 that concentrated solution is concentrated into 30 ℃ of density, or the volume that is concentrated into concentrated solution is 0.05～0.1 times of weight portion of medical material, the Cortex Mori concentrated solution is stand-by;
The Radix Puerariae medical material is used water extraction through after cutting or pulverizing, and extracting temperature is 50 ℃, and the total solvent amount is 22 times of weight portions of medical material, and extraction time is 3 times, each 2 hours; Extracting solution is merged; 70 ℃～75 ℃ following extracting solution concentrating under reduced pressure, centrifugal, with macroporous resin column on the supernatant of 3 times of medical material weight portions, upper prop finish the back water when being eluted to no total sugar Molish react negative, use 75% ethanol elution instead and begin to receive eluent, finish eluting when being negative reaction with ferric chloride reagent qualitative detection flavone, 50～90 ℃ of following alcohol eluens are concentrated into 30 ℃ of density and are about 1.31～1.35, or the volume of concentrated solution is 0.1～0.3 times of weight portion of medical material, the Radix Puerariae concentrated solution is stand-by;
60 ℃ of drying under reduced pressure behind Cortex Mori concentrated solution and the Radix Puerariae concentrated solution mix homogeneously promptly get the Mulberry pueraria root extract; Or with Cortex Mori concentrated solution and Radix Puerariae concentrated solution respectively routinely after decompression or the spray drying, remix, the Mulberry pueraria root extract;
The Mulberry pueraria root extract is added conventional excipients,, make concentrated pill, capsule, drop pill, granule, tablet, soft capsule, slow releasing agent, the oral liquid of clinical acceptance according to common process.
7. preparation of drug combination method as claimed in claim 5 is characterized in that the water in the wherein said extraction solvent can also substitute with alcoholic solution, and wherein the concentration of alcoholic solution is 10～90%.
8. preparation of drug combination method as claimed in claim 5 is characterized in that wherein said extracting method is that conventional the stirring extracted, soaked and extract or heating and refluxing extraction.
9. preparation of drug combination method as claimed in claim 5 is characterized in that wherein said macroporous resin is styrene type low pole or non-polar macroporous resin.
10. as the application of the arbitrary described pharmaceutical composition of claim 1-4 in the medicine of preparation treatment hyperglycemia, diabetes or its complication.
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| CN200610099050A CN101108207B (en) | 2006-07-17 | 2006-07-17 | Antidiabetic pharmaceutical composition and method of preparing the same |
| HK08102859.8A HK1108656A1 (en) | 2006-07-17 | 2008-03-12 | A pharmaceutical composition revealed pharmacological effect of lowing blood glucose and its preparative method |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579585A (en) * | 2011-01-07 | 2012-07-18 | 北京北大维信生物科技有限公司 | Blood sugar lowering medicinal composition and application thereof |
| CN102688295A (en) * | 2012-06-14 | 2012-09-26 | 上海中医药大学 | Chinese medicine composition for controlling metabolic diseases as well as preparation method and application thereof |
| CN102890124A (en) * | 2011-07-20 | 2013-01-23 | 北京北大维信生物科技有限公司 | Fingerprint constructing method of total flavonoid components and total alkaloids components in loranthus parasiticus-kudzuvine root preparation and quality detecting method |
| WO2013155995A1 (en) * | 2012-04-20 | 2013-10-24 | 北京北大维信生物科技有限公司 | Red yeast and kudzu root pharmaceutical composition for regulating blood lipids and preparation method therefor |
| CN104383111A (en) * | 2014-10-23 | 2015-03-04 | 广西金臣科技有限公司 | Kudzu plant fermentation broth and preparation method thereof |
| CN112322603A (en) * | 2020-12-19 | 2021-02-05 | 昆明理工大学 | Method for rapidly extracting alpha-glucosidase from fresh small intestine of rabbit |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1054053C (en) * | 1995-03-11 | 2000-07-05 | 朱立群 | Medicine for reducing blood sugar and its preparation method and use |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579585A (en) * | 2011-01-07 | 2012-07-18 | 北京北大维信生物科技有限公司 | Blood sugar lowering medicinal composition and application thereof |
| CN102579585B (en) * | 2011-01-07 | 2014-09-03 | 北京北大维信生物科技有限公司 | Blood sugar lowering medicinal composition and application thereof |
| CN102890124A (en) * | 2011-07-20 | 2013-01-23 | 北京北大维信生物科技有限公司 | Fingerprint constructing method of total flavonoid components and total alkaloids components in loranthus parasiticus-kudzuvine root preparation and quality detecting method |
| CN102890124B (en) * | 2011-07-20 | 2014-07-23 | 北京北大维信生物科技有限公司 | Fingerprint constructing method of total flavonoid components and total alkaloids components in loranthus parasiticus-kudzuvine root preparation and quality detecting method |
| WO2013155995A1 (en) * | 2012-04-20 | 2013-10-24 | 北京北大维信生物科技有限公司 | Red yeast and kudzu root pharmaceutical composition for regulating blood lipids and preparation method therefor |
| CN102688295A (en) * | 2012-06-14 | 2012-09-26 | 上海中医药大学 | Chinese medicine composition for controlling metabolic diseases as well as preparation method and application thereof |
| CN104383111A (en) * | 2014-10-23 | 2015-03-04 | 广西金臣科技有限公司 | Kudzu plant fermentation broth and preparation method thereof |
| CN112322603A (en) * | 2020-12-19 | 2021-02-05 | 昆明理工大学 | Method for rapidly extracting alpha-glucosidase from fresh small intestine of rabbit |
Also Published As
| Publication number | Publication date |
|---|---|
| HK1108656A1 (en) | 2008-05-16 |
| CN101108207B (en) | 2010-05-12 |
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