CN101584705B - Medicament composition for treating diabetes and complications of diabetes - Google Patents
Medicament composition for treating diabetes and complications of diabetes Download PDFInfo
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- CN101584705B CN101584705B CN2008100984679A CN200810098467A CN101584705B CN 101584705 B CN101584705 B CN 101584705B CN 2008100984679 A CN2008100984679 A CN 2008100984679A CN 200810098467 A CN200810098467 A CN 200810098467A CN 101584705 B CN101584705 B CN 101584705B
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Abstract
The invention provides an oral medicament composition for treating diabetes and the complications of diabetes, belonging to the field of medicines. The oral medicament composition for treating diabetes and the complications of diabetes comprises migltol and heparin or low molecular heparin or a medicinal salt of the heparin or the low molecular heparin in the weight ratio of 1:0.1-9. The medicament composition plays a good synergic action on lowering blood sugar, can reduce the complications of diabetes and generate positive effect on the prognosis of a diabetic who takes the oral medicament composition for a long time so that the oral medicament composition for treating diabetes and the complications of diabetes is quite beneficial to the recovery of the diabetic.
Description
Technical field
The present invention relates to a kind of new pharmaceutical composition for the treatment of diabetes and complication thereof, belong to field of medicaments.
Background technology
Diabetes are a kind of incretion metabolism diseases, are owing to the relative or absolute not enough carbohydate metabolism disorder that causes of insulin in the body, cause the water of sugar, protein, fat and secondary, the disease of metabolic disturbance of electrolyte.Diabetes are divided two types clinically: insulin dependent diabetes mellitus (IDDM) (being type i diabetes), non-insulin-dependent diabetes mellitus (being type ii diabetes).Wherein, the type ii diabetes rate is very high, accounts for about 90% of onset diabetes number.The harm of diabetes is mainly from complication, and its incidence rate is very high, has caused high fatality rate and high disability rate.Studies show that had 30%～40% patient a kind of complication to take place in 10 years behind the onset diabetes to I haven't seen you for ages.Common diabetic complication has nephropathy that diabetes cause, eyes pathological changes, nervous system lesion, cardiovascular pathological changes, fatty liver etc.
World Health Organization (WHO) announces recently, nineteen ninety-five, whole world diabetics was only about 3,000 ten thousand people, and to increasing to 1.35 hundred million in 1997, predict according to the authoritative sources, to reach 2.4 hundred million by 2010,, will have 3.3 hundred million people to be diagnosed as diabetes by 2025, and mortality rate is only second to malignant tumor and cardiovascular diseases, is the third-largest disease that jeopardizes human life's health.
Along with the raising of living standards of the people, the incidence rate of China's diabetics and mortality rate are also increasing severely year by year.The finding that distributes from China each department, the eighties China's diabetics sickness rate less than 1%, risen to 2.65% by 1997, and more increased rapidly in recent years with annual 0.1% speed, formed an ill colony that can not be ignored.At present, China has entered the diabetes outbreak period, increases by 3000 of patients every day at least.The treatment of diabetes and complication thereof and prevent extremely urgent.
Miglitol (Miglitol) is a kind of novel antidiabetic drug of German Baeyer drugmaker early 1980s research and development, is a kind of new small intestinal α glucosidase inhibitor.The discovery of miglitol comes from the research to the nojirimycin that is produced by microbial fermentation, finds that this former antibiotic that is used as anti-salmonella has stronger alpha-glucosaccharase enzyme inhibition, becomes first found amylase inhibitor.1-deoxynojirimycin (1-deoxynojirimycin) is got by the nojirimycin reduction, also can be produced by multiple streptomycete, bacillus cereus and bacillus subtilis, has glycosidase inhibiting function equally.N-replacement-1-deoxynojirimycin has better hypoglycemic effect, and miglitol is exactly one of them.The structure of miglitol is similar to glucose, and reversibly the false monosaccharide alpha-Glucosidase of competitive inhibition reduces the metabolism of monosaccharide, is reduced in the absorption of small intestinal.
Heparin (Heparinum) all can prolong the anticoagulant of clotting time for the inside and outside.Its blood coagulation resisting function is very complicated, and is all influential to many links of coagulation process, and its effect can be by several aspects: 1. anticoagulant kinase formation and effect, thereby the obstruction thrombinogen becomes thrombin; 2. in higher concentration fashion the antithrombase effect is arranged, make Fibrinogen can not become fibrin; 3. can stop hematoblastic coagulation and destruction etc.At present, heparin is mainly used in control a variety of causes thrombosis and the thromboembolism that cause, the disseminated inravascular coagulation disease that causes as myocardial infarction, pulmonary infarction, cerebral vessels embolism, peripheral vein thrombosis, vascular surgery and a variety of causes etc.The early stage application is to prevent the exhaustion of Fibrinogen and thrombin; When replacing structure same regimen acid salt or extracorporeal circulation when also can be used for transfusing blood as external anticoagulant.In addition, Anthology of Medicine, August2003, Vol.22, the fourth phase " calciparine is to the influence of type 2 diabetes mellitus " has been discussed the assistant hypoglycemic effect of calciparine to the type ii diabetes people, but does not provide the specific embodiments of calciparine and other antidiabetic drug use in conjunction.
Although oral antidiabetic drug is of a great variety on the market, up to now, also there is not which kind of medicine to remain within the target zone for a long time with the HbAlc level of one's own with the type ii diabetes patient.This shows that the novel antidiabetic drug that exploitation has brand-new mechanism of action and preferable risk/beneficial ratio has become the vital task that medical workers need to be resolved hurrily.
In a word, existing oral antidiabetic thing exists many deficiencies, and in conjunction with the Pathophysiology characteristics of diabetes and complication thereof, the medicine that enlarges thinking searching newtype is the research focus for the treatment of diabetes.
Summary of the invention
In order to strengthen blood sugar reducing function and to overcome the individually dosed toxic and side effects of bringing, we adopt the medicine of two kinds of different mechanism of action are made compound preparation, maximize favourable factors and minimize unfavourable ones, and the performance synergism reduces negative effect simultaneously.By animal experiment study, we find that miglitol combined with heparin or Low molecular heparin or officinal salt are treated diabetes and complication has obtained good therapeutic effect.
The invention provides the combination of oral medication of a kind of convenience, safe and effective treatment diabetes and complication thereof.This pharmaceutical composition comprises miglitol and heparin or the Low molecular heparin or the officinal salt of special ratios, by a large amount of preparation experiment and pharmacodynamics tests, we find that the weight ratio of miglitol and heparin sodium or low molecular sodium heparin is at 1: 0.1～9 o'clock, and the present invention has effect preferably.Wherein, tiring of the heparin that relates among all technical schemes of the present invention and the embodiment or its officinal salt is 179U/mg, and tiring of Low molecular heparin or its officinal salt is 104.4U/mg.
The inventor makes this compound recipe dosage forms such as capsule, conventional tablet, effervescent tablet, enteric coatel tablets, slow releasing tablet, intra-gastric floating tablet.The selected adjuvant of the present invention has: starch, pregelatinized Starch, starch slurry, dextrin, microcrystalline Cellulose, vitamin E, hydroxypropyl emthylcellulose, low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, Polyethylene Glycol (PEG), sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, mannitol, lactose, polyvinylpyrrolidone (PVP), crospolyvinylpyrrolidone, magnesium stearate, Pulvis Talci, micropowder silica gel, sodium bicarbonate, sodium carbonate, in the enteric coating powder partly or entirely.
Compared with prior art, advantage of the present invention is:
1, synergism is arranged, pharmaceutical composition of the present invention has very strong hypoglycemic effect.Heparin sodium or low molecular sodium heparin are brought into play hypoglycemic activity with miglitol jointly by different mechanism of action.Suppressing carbohydrate breakdown is glucose, reduces the intake to glucose, improves the utilization of body to the glucose that absorbed, thereby greatly reduces blood sugar level.In the picked-up of control glucose with improve under the dual function to the utilization of glucose, blood sugar decreasing effect significantly improves, and the drug combination for extensive patients and doctor provide scientific and efficient has made things convenient for the patient.
2, in effective blood sugar lowering, can reduce the complication of diabetes.Diabetic nephropathy is the common complication that threatens diabetics.We have proved that by animal experiment the present invention has good synergism for reducing microdose urine protein, and the compound preparation of heparin sodium or low molecular sodium heparin and miglitol has better curative effect for the control diabetic nephropathy.
3. pharmaceutical composition of the present invention is through the confirmation of pharmacodynamic experiment, obtained good hypoglycemic effect after the long term administration, good hypoglycemic effect is indicating that pharmaceutical composition of the present invention will produce active influence for the prognosis of diabetes, has brought hope for the recovery from illness of diabetics.
Heparin sodium or low molecular sodium heparin and miglitol compound recipe are in that to reduce post-prandial glycemia, fasting glucose, glycolated hemoglobin (HbAlc) level, the microdose urine protein curative effect aspect horizontal best.
The specific embodiment
Embodiment 1
Prescription
Heparin sodium 10g
Miglitol 100g
Microcrystalline Cellulose 250g
8% Gonak is an amount of
Low-substituted hydroxypropyl cellulose 120g
Magnesium stearate 5g
Preparation technology: heparin sodium and miglitol are crossed 100 mesh sieves, microcrystalline Cellulose and low-substituted hydroxypropyl cellulose are crossed 80 sieves, take by weighing heparin sodium, miglitol and low-substituted hydroxypropyl cellulose, the microcrystalline Cellulose mix homogeneously of recipe quantity, adding 8% Gonak granulates in right amount, 60 ℃ of dryings, 16 mesh sieve granulate, the magnesium stearate mixing of adding recipe quantity in the dried granule, tabletting is promptly.
Embodiment 2
Heparin sodium 450g
Miglitol 50g
Microcrystalline Cellulose 600g
PEG6% solution is an amount of
Carboxymethylcellulose calcium 255g
Magnesium stearate 7.5g
Preparation technology: with embodiment 1.
Embodiment 3
Low molecular weight heparin sodium 20g
Miglitol 100g
Pregelatinized Starch 400g
Sodium carboxymethyl cellulose 1% solution is an amount of
The enteric coating powder is an amount of
Carboxymethylcellulose calcium 60g
Magnesium stearate 4.5g
Preparation technology: tablet technology is made into the tablet (ball core) of required specification routinely, and reuse enteric coating powder coating gets final product.
Embodiment 4
Low molecular weight calcium heparin 50g
Miglitol 100g
Pregelatinized Starch 550g
PEG6% solution is an amount of
Carboxymethylcellulose calcium 75g
Magnesium stearate 5.5g
Preparation technology: with embodiment 3.
Embodiment 5
Calciparine 300g
Miglitol 50g
Pregelatinized Starch 300g
Mannitol 250g
Lactose 200g
95% alcoholic solution of 6%PVP is an amount of
Micropowder silica gel 17g
Preparation technology: 100 mesh sieves are crossed in the calciparine in will writing out a prescription, miglitol, pregelatinized Starch, mannitol, lactose and micropowder silica gel respectively, mixing, and 95% alcoholic solution that adds 6%PVP is granulated in right amount, 60 ℃ of oven dry, 18 mesh sieve granulate, capsule charge gets final product.
Embodiment 6
Heparin sodium 200g
Miglitol 50g
Microcrystalline Cellulose 250g
Carboxymethylcellulose calcium 90g
Lactose 250g
95% the alcoholic solution of 6%PVP is an amount of
Micropowder silica gel 15g
Preparation technology: with embodiment 5.
Embodiment 7
Heparin sodium 100g
Miglitol 50g
Carboxymethylcellulose calcium 150g
Crospolyvinylpyrrolidone 150g
Microcrystalline Cellulose 320g
10% starch slurry is an amount of
Magnesium stearate 10g
Sodium bicarbonate 80g
Citric acid 500g
Preparation technology: the preparation technology of effervescent tablet is prepared into required effervescent tablet and gets final product routinely.
Embodiment 8
Heparin sodium 5g
Miglitol 50g
Crosslinked carboxymethyl fecula sodium 200g
Microcrystalline Cellulose 120g
Ethyl cellulose 4g
Vitamin E 10g
Magnesium stearate 3.5g
Preparation technology: be prepared into slow releasing tablet by the preparation technology of slow releasing tablet and get final product.
Embodiment 9
Low molecular sodium heparin 100g
Miglitol 25g
Crosslinked carboxymethyl fecula sodium 350g
Microcrystalline Cellulose 150g
Vitamin E 15g
Magnesium stearate 4.5g
Preparation technology: with low molecular sodium heparin through pulverizing, the operation of sieving, with miglitol and other auxiliary materials and mixing of recipe quantity, the preparation technology of tablet is prepared into required tablet and gets final product routinely then.
Embodiment 10 miglitol heparin compound recipes are to the influence of diabetes model rat
The preparation of 1 animal model
Body weight 160～180g SD rat, male and female half and half, rat fasting 18h is fed with high-sugar-fat-diet (albumen select matter 5%, carbohydrate 60% wherein sucrose is 30%, wherein to refine Adeps Sus domestica be 30% to fat 32%) after 4 weeks in southern Shandong pharmacy Experimental Animal Center breeding earlier.Lumbar injection 0.6% streptozotocin (STZ) 30mg/kg, STZ is dissolved in PH4.0, and in the 0.1mol/L citric acid-sodium citrate buffer, each dose uses up in 10min.Blank group rats by intraperitoneal injection equal-volume citric acid-sodium citrate buffer, the normal raising.Docking is got blood and is surveyed whole blood sugar after 5 days, is the modeling success with blood glucose value level＞10.0mmol/L person.
2 grouping and administrations
Modeling success rat is divided into following each group at random according to blood sugar level:
Model group: the normal saline of equal volume
Miglitol group: 5mg/ (kg.d) miglitol
Heparin group: 2.5mg/ (kg.d) heparin sodium
Compound recipe low dose group: 2.5mg/ (kg.d) miglitol+1.25mg/ (kg.d) heparin sodium
Dosage group: 5mg/ (kg.d) miglitol+2.5mg/ (kg.d) heparin sodium in the compound recipe
Compound recipe high dose group: 10mg/ (kg.d) miglitol+5mg/ (kg.d) heparin sodium
Every group 8, irritate stomach twice every day, irritate stomach fasting in preceding 8 hours, give feedstuff at once, continuous 10 weeks behind the filling stomach.
3 detect index
3.1 the mensuration of blood glucose
After modeling success rat random packet, according to dosage gastric infusion in continuous 10 weeks, is normally raised.All rats are respectively at getting tail vein detection fasting glucose (FBG), feed back 2h blood glucose (PBG) before treating and in treatment 4 weeks of back weekly.The blood sample that takes out is put into protein precipitant, and after room temperature was placed 7min, centrifugal 5min (3000r/min) got supernatant, surveyed whole blood sugar with glucose oxidase method.
Experimental result: no matter be fasting glucose or 2h blood glucose after the meal, the low group of compound recipe more all has significant difference with model group, and group and model group relatively have utmost point significant difference in high group of compound recipe and the compound recipe.Compound recipe group and miglitol group are relatively having significant difference aspect the fasting glucose reducing, and have only the low group of compound recipe not have significant difference aspect the 2h blood glucose reducing after the meal.Compound recipe group and heparin group are relatively reducing fasting glucose and significant difference or utmost point significant difference are all being arranged aspect the 2h blood glucose after the meal.It can be said that brightly, miglitol heparin sodium compound recipe has good synergism for the blood glucose that reduces diabetes rat.
Table 1 miglitol heparin sodium is to the influence of diabetes rat fasting glucose and feed back 2h blood glucose
*Compare P＜0.05 with model group;
*Compare P＜0.01 with model group;
#Compare P＜0.05 with the miglitol group;
﹠amp;Compare P＜0.05 with heparin group;
﹠amp; ﹠amp;Compare P＜0.01 with heparin group
3.2 the mensuration of glycolated hemoglobin (HbAlc)
(grouping, the same blood sugar detection of administration) fasting 12h after the last administration, etherization, eye socket is got blood, presses description mensuration HbAlc in the test kit.
Experimental result: the low group of compound recipe has been compared significant difference with model group, and group, the high group of compound recipe have been compared utmost point significant difference in the compound recipe with model group.Group, high group relatively have significant difference with the miglitol group in the compound recipe.Compare with heparin group, each compound dose group all has significant difference.Illustrate that miglitol heparin sodium compound recipe has good synergy for reducing HbAlc.
Table 2 miglitol heparin sodium compound recipe is to the influence of diabetes rat HbAlc
*Compare P＜0.05 with model group;
*Compare P＜0.01 with model group;
#Compare P＜0.05 with the miglitol group;
﹠amp;Compare P＜0.05 with heparin group.
3.3 micro-albuminised mensuration in the urine:
Reagent: 1, the glacial acetic acid solution of 10% (v/v) (PH2.8).
2,0.303mol/L glycine-glacial acetic acid buffer (PH3.0): take by weighing the 22.72g glycine, be diluted to 1000ml, add NaN with 10% glacial acetic acid solution
3100mg, the room temperature sealing can be stablized 1 year.
3, bromophenol blue (1.924mmol/L) stock solution: accurately take by weighing 257,36mgBPB, molten to 200ml with dehydrated alcohol, 4 ℃ of refrigerators can be stablized 1 year.
4, bromophenol blue (0.231mmol/L) developer: get the 60mlBPB stock solution, add 2.5mlTriton X-100, be diluted to 500ml with glycine-glacial acetic acid buffer, the room temperature sealing can be preserved 1 year.
The collection of specimen and detection: in the 12nd week rat is put in the metabolic cage respectively and raises, collect 12 hours overnight urine, accurate recording urine amount.Get 4ml, after sodium azide was handled, centrifugal (2000r/min) 10min got supernatant and puts-20 ℃ of refrigerators and preserves urinaryalbumin to be measured.The albumin standards 400 of getting respective concentration respectively adds 200 developers in the cup of correspondence, mixing (preventing to produce bubble) is used ultraviolet spectrophotometer, measures absorbance A down in 600nm.
Experimental result: the low group of compound recipe relatively has significant difference with model group, and group relatively has utmost point significant difference with model group in high group of compound recipe and the compound recipe.The high group of group and compound recipe relatively has significant difference with miglitol group and heparin group respectively in the compound recipe.The result shows that miglitol heparin sodium compound recipe has good synergism aspect the diabetes rat microdose urine protein influencing.
Table 3 miglitol heparin sodium compound recipe is to the influence of diabetes rat microdose urine protein
*Compare P＜0.05 with model group;
*Compare P＜0.01 with model group;
#Compare P＜0.05 with the miglitol group;
﹠amp;Compare P＜0.05 with heparin group.
Embodiment 11 miglitol low molecular sodium heparins are to the influence of spontaneous diabetic mice
The preparation of 1 animal model
Spontaneous diabetes animal model: the mode of inheritance of fat hyperglycemia mice (C57BL/6 ob/ob mice) is autosomal recessive gene heredity.Build is extremely fat.Hyperglycemia, glycosuria promptly take place in early days, but do not see ketosis and stupor.Serum insulin levels increases, and obvious insulin resistance is arranged, even only produce faint hypoglycemic activity up to the insulin of 400IU this Mus.The visible islets of langerhans hypertrophy of histopathologic examination, hypertrophy, insulin content increases, but hepatic glycogen is stored minimizing.
2 grouping and administrations
Fat hyperglycemia mice is divided into following 6 groups at random according to blood sugar level:
Model group: the normal saline of equal volume
Miglitol group: 7.5mg/ (kg.d) miglitol
Low molecular heparin group: 1.2mg/ (kg.d) low molecular sodium heparin
The low group of compound recipe: 3.75mg/ (kg.d) miglitol+0.6mg/ (kg.d) low molecular sodium heparin
Organize in the compound recipe: 7.5mg/ (kg.d) miglitol+1.2mg/ (kg.d) low molecular sodium heparin
The high group of compound recipe: 15mg/ (kg.d) miglitol+2.4mg/ (kg.d) low molecular sodium heparin
Every group 10, irritate stomach twice every day, irritate stomach fasting in preceding 8 hours, give feedstuff at once, continuous 10 weeks behind the filling stomach.Fasting glucose, 2h blood glucose and glycolated hemoglobin (HbAlc) are after the meal measured in blood sampling.
3 detect index
3.1 the mensuration of blood glucose
After fat hyperglycemia mice random packet, according to dosage gastric infusion in continuous 10 weeks, is normally raised.All mices are respectively at treating preceding and 10 all interior per 2 weeks of treatment back extracting tail veins and detect fasting glucose (FBG), 2h blood glucose (PBG) after taking food.The blood sample that takes out is put into protein precipitant, after room temperature is placed 7min, centrifugal 5min, 3000r/min.Get supernatant, survey whole blood sugar with glucose oxidase method.
Experimental result: no matter be fasting glucose or feed back 2h blood glucose, compound recipe group and model group all have significant difference or utmost point significant difference; Compound recipe group and miglitol group are relatively having significant difference or utmost point significant difference aspect the fasting glucose reducing, and have only the low group of compound recipe not have significant difference aspect the 2h blood glucose reducing after the meal.Compound recipe group and Low molecular heparin group group are relatively reducing fasting glucose and significant difference or utmost point significant difference are all being arranged aspect the 2h blood glucose after the meal.This explanation miglitol low molecular sodium heparin compound recipe has good synergism for the blood glucose that reduces diabetic mice.
Table 4 miglitol low molecular sodium heparin is to the influence of diabetic mice fasting glucose and feed back 2h blood glucose
*Compare P＜0.05 with model group,
*Compare P＜0.01 with model group,
#Compare P＜0.05 with miglitol,
##Compare P＜0.01 with miglitol,
﹠amp;Compare P＜0.05 with the Low molecular heparin group,
﹠amp; ﹠amp;Compare P＜0.01 with the Low molecular heparin group.
3.2 the mensuration of glycolated hemoglobin (HbAlc)
(grouping, the same blood sugar detection of administration) fasting 12h after the last administration, etherization, eye socket is got blood, presses description mensuration HbAlc in the test kit.
Experimental result: compound recipe group and model group relatively have significant difference or utmost point significant difference.Compound recipe group and miglitol, Low molecular heparin group relatively have significant difference.Illustrate that miglitol low molecular sodium heparin compound recipe has good synergy for reducing HbAlc.
Table 5 miglitol low molecular sodium heparin compound recipe is to the influence of diabetic mice HbAlc
*Compare P＜0.05 with model group;
*Compare P＜0.01 with model group;
#Compare P＜0.05 with the miglitol group;
﹠amp;Compare P＜0.05 with the Low molecular heparin group.
3.3 micro-albuminised mensuration in the urine
Experimental procedure is with embodiment 10.
Experimental result: compound recipe group and model group relatively have significant difference or utmost point significant difference; The high group of group and compound recipe relatively has significant difference with the miglitol group in the compound recipe; Each group of compound recipe has been compared significant difference with group, and the high group of compound recipe has utmost point significant difference.It can be said that bright miglitol and low molecular sodium heparin compound recipe have good synergy for reducing urinaryalbumin.
Table 6 miglitol low molecular sodium heparin compound recipe is to the influence of diabetic mice urinaryalbumin
*Compare P＜0.05 with model group;
*Compare P＜0.01 with model group;
#Compare P＜0.05 with the miglitol group;
﹠amp;Compare P＜0.05 with the Low molecular heparin group;
﹠amp; ﹠amp;Compare P＜0.01 with the Low molecular heparin group.
Claims (3)
1. a new pharmaceutical composition for the treatment of diabetes and complication thereof is characterized in that, it contains miglitol and heparin or Low molecular heparin or its officinal salt.
2. pharmaceutical composition as claimed in claim 1, it is characterized in that, the weight ratio of miglitol and heparin or its officinal salt or Low molecular heparin or its officinal salt is 1: 0.1～9, wherein tiring of heparin or its officinal salt is 179U/mg, and tiring of Low molecular heparin or its officinal salt is 104.4U/mg.
3. as the arbitrary described pharmaceutical composition of claim 1-2, it is characterized in that it is capsule, conventional tablet, effervescent tablet, enteric coatel tablets, slow releasing tablet or intra-gastric floating tablet.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0557887A2 (en) * | 1992-02-25 | 1993-09-01 | OPOCRIN S.p.A. | Polysaccharide derivatives of heparin, heparan sulphate, fraction and fragments thereof, process for their preparation and pharmaceutical compositions containing them |
| CN1274282A (en) * | 1997-06-18 | 2000-11-22 | 史密丝克莱恩比彻姆有限公司 | Treatment of diabetes with thiazolidinedione and Alpha-glucosidase inhibitor |
| CN101121004A (en) * | 2006-08-08 | 2008-02-13 | 鲁南制药集团股份有限公司 | Medicine composition containing insulin intensifier and miglitol |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0557887A2 (en) * | 1992-02-25 | 1993-09-01 | OPOCRIN S.p.A. | Polysaccharide derivatives of heparin, heparan sulphate, fraction and fragments thereof, process for their preparation and pharmaceutical compositions containing them |
| CN1274282A (en) * | 1997-06-18 | 2000-11-22 | 史密丝克莱恩比彻姆有限公司 | Treatment of diabetes with thiazolidinedione and Alpha-glucosidase inhibitor |
| CN101121004A (en) * | 2006-08-08 | 2008-02-13 | 鲁南制药集团股份有限公司 | Medicine composition containing insulin intensifier and miglitol |
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Effective date of registration: 20211210 Address after: 276006 No. 209 Hongqi Road, Shandong, Linyi Patentee after: LUNAN HOPE PHARMACEUTICAL Co.,Ltd. Address before: 276005 No. 209 Hongqi Road, Shandong, Linyi Patentee before: LUNAN PHARMACEUTICAL Group Corp. |
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