CN101214257A - Medicinal composition for treating diabetes chronic complication and preparation method thereof - Google Patents
Medicinal composition for treating diabetes chronic complication and preparation method thereof Download PDFInfo
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- CN101214257A CN101214257A CNA2008100558205A CN200810055820A CN101214257A CN 101214257 A CN101214257 A CN 101214257A CN A2008100558205 A CNA2008100558205 A CN A2008100558205A CN 200810055820 A CN200810055820 A CN 200810055820A CN 101214257 A CN101214257 A CN 101214257A
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Abstract
The present invention relates to a series of medicine combinations for remedying diabetic chronic complication and a preparation method thereof, which are compound oral preparations (comprising troche, dispersible tablet, effervescent tablet, capsule preparation, soft capsule and granule preparation) which are mainly made from at least two active components of mecobalamin, cobamamide, vitamin B12, epalrestat, lipoic acid and calcium dobesilate and pharmic acceptable auxiliary materials. The preferential combinations of the present invention are the mecobalamin plus the lipoic acid, the mecobalamin and the lipoic acid plus the calcium dobesilate, the mecobalamin and the epalrestat plus the calcium dobesilate, the mecobalamin, the lipoic acid and the epalrestat plus the calcium dobesilate, and the mecobalamin and the vitamin B12 plus cobamamide. The present invention is mainly used for remedying the nervous lesion of the diabetic chronic complication.
Description
Technical field
The present invention relates to a series of pharmaceutical compositions that are used for the treatment of chronic complicating diseases of diabetes and preparation method thereof, belong to medical technical field.
Background technology
Diabetic peripheral neuropathy (DPN) is relevant with multiple factor, the metabolism disorder as sugar alcohol, and the activity of Na+-K+-ATP enzyme reduces, and disturbance of blood circulation causes the hypercoagulability of blood, the sclerosis of unusual, the blood vessel of hemocyte etc.That the DPN blood samples of patients has is dense, sticking, coagulate, poly-and hemorheology reaches paramophia unusually, vascular endothelial cell is impaired, blood vessel especially wall of micrangium thickens, permeability increases and microthrombusis, cause nervous tissue's ischemia, anoxia, cause that oxidative stress strengthens, free radical generates and increases, cause a series of oxidation reactions, cause nerve injury.The unified machine-processed theory of diabetic complication proposes, and it too much is the common mechanism that causes comprising the chronic complicating diseases of diabetes of diabetic peripheral neuropathy that the mitochondrion superoxides produces.It too much is the activated reason of main path that high sugar mediates tissue injury that mitochondrion electrontransport resplratory chain superoxides produces.Known some metabolism at present and signal transduction pathway such as polyhydric alcohol path, DG-Protein kinase C (DAG-PKC) path, hexosamine approach, albumen nonenzymatic glycosylation and oxidative stress play crucial effect in the developing of chronic complicating diseases of diabetes.The polyhydric alcohol path is made up of two key enzymes, one is aldose reductase (AR), another is a sorbito dehy drogenase, AR catalysis conversion of glucose under the help of NADPH is a sorbitol, also but the catalysis galactose is converted into galactitol, and sorbito dehy drogenase catalyzing sorbitol under the help of NAD+ is converted into fructose.The fructose that generates is too much, and most and sorbitol is piled up in cell together, thereby causes the interior osmotic pressure of neurocyte to increase, and causes edema, degeneration, necrosis.Become with far-end primary sensation neuropathy and symmetry motor neuron and to see that cardinal symptom is glove, socks sample sensory disturbance more, and with pain, numbness, send out cool, unable and amyotrophy etc.
Mecobalamin is a kind of endogenic actimide, participates in the one carbon unit circulation, plays an important role in the transmethylase course of reaction by the homocysteine synthetic methionine.It is synthetic by nucleic acid and protein and neural myelin in the promotion neurocyte, thus the peripheral nerve of repairing damage.This product can also promote aixs cylinder transportation function and axon regeneration; make the transportation normalization of the inductive diabetic sciatic nerve aixs cylinder of streptozotocin skelemin; inhibited to drug-induced nerve degeneration, the nerve degeneration that causes as amycin, acrylamide, vincristine and spontaneous hypertension rat sacred disease etc.Mecobalamin can make the nerve synapse transmission of delay and neurotransmitter minimizing recover normal, induces by improving nerve fiber irritability recovery end plate potential, can make to raise with acetylcholine in the rat brain of choline shortage feedstuff to return to normal level.
Cobamamide is the congener of cyanogen cobalt type vitamin B12, be that its CN base is replaced by the adenine glycosides, become 5 ' one deoxyadenosine cobalt amine, it is one of two kinds of active coenzyme forms of vitamin B12 in the body, is the cell growth and breeding and keeps the complete necessary material of nervous system myelin.This product can directly absorb, and is active strong, strong with the histiocyte affinity, drains slower.Be used for nerve illness such as polyneuritis, radiculitis, trigeminal neuralgia, sciatica, neural paralysis, trophic nerve disease patient.
It is synthetic that vitamin B12 participates in thymidylic acid indirectly.Need be converted into methylcobalamin and cobamamide in vivo makes it have activity, B12 can assist folic acid to regulate erythrocytic generation and help the utilization of ferrum. and digestive function is normal, the digestion of food and proteinic synthetic, and the metabolism of fat and sugar class all needs vitamin B12. this product also impels Isosuccinic acid to change succinic acid in addition, participate in tricarboxylic cycle, so the myelin lipid that also can affect the nerves when lacking is synthetic, so B12 helps to prevent nerve injury, promote normal growth promoter, and prevent the effect of neural demyelination.
Epalrestat is an aldose reductase inhibitor, reversibly to suppress conversion of glucose in the polyhydric alcohol metabolism relevant with the pathogenesis of diabetic complication is that the aldose reductase of sorbitol plays a role, the known sorbitol cell function that can affect the nerves, it is accumulated in neuron and can cause that diabetic arranges estheticokinetic peripheral nervous disease symptoms.Epalrestat is the aldose reductase specific inhibitor of present unique listing, and epalrestat can alleviate the oxidative stress of diabetic individual, and the Profilin nonenzymatic glycosylation.Epalrestat is mainly in order to the treatment diabetic neuropathy, and is not only effective to diabetic peripheral neuropathy, and also effective to autonomic neuropathy.Epalrestat also has certain therapeutical effect to diabetictrunk angiopathy, diabetic nephropathy etc., can also increase the generation of diabetic neutrophilic granulocyte oxygen-derived free radicals and improves disease and go into resistance.The adverse reaction rate of epalrestat is low, be a kind of to chronic complicating diseases of diabetes (particularly diabetic neuropathy) effectively and safe drugs.
Thioctic acid is a kind of powerful antioxidant, for the treatment of diabetic peripheral neuropathy provides a new road, thioctic acid is that the cofactor of complex works as pyruvic dehydrogenase and α glutatate dehydrogenase-cyclophorase, thioctic acid can be converted into the reduced form dihydrolipoic acid in vivo, and the two all is a powerful antioxidant.Can remove free radical, other antioxidants of regenerating, by preventing neural interior oxidative stress status, increase blood flow in the neurotrophy blood vessel, increase mechanism such as Na-K-ATP activity, thioctic acid can suppress aldose reductase in addition, thereby can stop glucose or galactose to transform into sorbitol, improves the diabetic peripheral neuropathy symptom.
Calcium dobesilate is a kind of microcirculation improvement new drug of clinical practice, calcium dobesilate is by adjusting and improve the permeability and the pliability of capillary wall, increase its resistance, reduce macromole plasma protein, Fibrinogen and ball egg level certainly, regulate the ratio of albumin and globulin, strengthen erythrocytic pliability and reduce their the poly-property of height, can also the activation fiber protein dissolution, thereby viscosity of blood is reduced, reduce platelet aggregation, suppress the inductive thrombosis of adenosine diphosphate (ADP) (adp), improve the backflow of lymph fluid.Also can suppress the high osmosis of blood capillary that vaso-active substance (histamine, 5-hydroxy tryptamine, Kallidin I, hyaluronidase, prostaglandin) causes, promote the synthetic of basement membrane collagen, thereby play the microvascular effect of protection; Calcium dobesilate has hypoglycemic effect in addition, so the microangiopathy degeneration disease that calcium dobesilate causes diabetes especially has obvious inhibitory action and changes retroaction
Above-mentioned each mechanism of drug action:
Above-mentioned various kinds of drug all has direct or indirect effect to diabetic neuropathy, at present at the treatment chronic complicating diseases of diabetes, especially the types of drugs of neuropathy is less, and effect is limited to, so will be to the medicative medicine of diabetic neuropathy, make compound preparation according to reasonable combination and proportioning and use, will improve the availability and the curative effect of medicine greatly.
By retrieval, do not see the compound preparation pertinent literature and the patent report of above-mentioned all kinds of medicines
Summary of the invention
The present invention relates to a series of pharmaceutical compositions that are used for the treatment of chronic complicating diseases of diabetes, mainly make compound preparation by at least two kinds of active component in mecobalamin, cobamamide, vitamin B12, epalrestat, thioctic acid, the calcium dobesilate and acceptable accessories.According to the site that all kinds of medicines mainly act on, can above-mentioned various medicines be made up according to certain developmental stage of the disease of wanting to control.For example: if totally prevent chronic complicating diseases, can be with calcium dobesilate and thioctic acid combination, because the generation of diabetic angiopathy and free radical is a total mechanism of chronic complicating diseases of diabetes morbidity.So the generation of chronic complicating diseases can be prevented or control to calcium dobesilate and thioctic acid common application.If want to prevent and control the further deterioration of neuropathy, then to contain a kind of in thioctic acid and the epalrestat in the compound recipe at least, because the polyhydric alcohol path peculiar approach that is nerve injury, thioctic acid and epalrestat can be special acts on this step.If want the nerve of damage is repaired to keep function of nervous system, then in the compound recipe vancomin must be arranged, because the vancomin very good neural renovation agent that is a kind of curative effect, it can not block the carrying out of damage, only can repair and promotes regeneration the nerve after the damage.
The neuropathy that the present invention is primarily aimed in the chronic complicating diseases of diabetes is made up above-mentioned all kinds of medicines, so preferred composition following (but and only limiting to this) wherein: mecobalamin+thioctic acid, mecobalamin+thioctic acid+calcium dobesilate, mecobalamin+epalrestat+calcium dobesilate, mecobalamin+thioctic acid+epalrestat+calcium dobesilate, mecobalamin+vitamin B12+cobamamide.
In described mecobalamin+thioctic acid compositions, mecobalamin unit administration dosage is 0.1～2.0mg, is preferably 0.5mg, and the unit administration dosage 10～500mg of thioctic acid is preferably 100mg.
In described mecobalamin+thioctic acid+phenolsulfonic acid calcium composition, the unit administration dosage of mecobalamin is 0.1～2.0mg, is preferably 0.5mg, the unit administration dosage 10～500mg of thioctic acid, be preferably 100mg, the unit administration dosage of calcium dobesilate is 100～2000mg, is preferably 500mg.
In described mecobalamin+epalrestat+phenolsulfonic acid calcium composition, the unit administration dosage of mecobalamin is 0.1～2.0mg, be preferably 0.5mg, the unit administration dosage of epalrestat is 10～200mg, be preferably 50mg, the unit administration dosage of calcium dobesilate is 100～2000mg, is preferably 500mg.
In described mecobalamin+thioctic acid+epalrestat+phenolsulfonic acid calcium composition, the unit administration dosage of mecobalamin is 0.1～2.0mg, be preferably 0.5mg, the unit administration dosage 10～500mg of thioctic acid, be preferably 100mg, the unit administration dosage of epalrestat is 10～200mg, is preferably 50mg, the unit administration dosage of calcium dobesilate is 100～2000mg, is preferably 500mg.
In described mecobalamin+vitamin B12+cobamamide compositions, the unit administration dosage of mecobalamin is 0.1～2.0mg, be preferably 0.5mg, the unit administration dosage of vitamin B12 is 0.005～0.20mg, be preferably 0.5mg, the unit administration dosage that is preferably cobamamide is 0.05～2mg, is preferably 0.25～0.5mg.
Above-described various pharmaceutical composition can be made oral formulations (comprising tablet, dispersible tablet, effervescent tablet, capsule, soft capsule, granule) with acceptable accessories.
Above-described various pharmaceutical composition is mainly used in the neuropathy in the treatment chronic complicating diseases of diabetes.But do not get rid of therapeutical effect to other chronic complicating diseases of diabetes except that neuropathy.
The present invention also provides following pharmacological evaluation, with the effect and the suitability that further specifies the present composition
1. experimental technique
STZ rat model and grouping: rat fasting 16h, streptozotocin is dissolved in 0.1mol/L citrate buffer solution (pH 4.5) and is made into 1% solution, give rats by intraperitoneal injection with 65～70mg/kg dosage, the 72h posterior orbit is got blood, measure blood glucose, select the parallel grouping of the animal pattern of blood glucose more than 16mmol/L.Matched group only gives that citrate buffer solution is parallel to experimentize.The experiment be divided into 5 groups: matched group (A), model group (B), mecobalamin+thioctic acid group (C) (1.0mg/kg+0.2g/kg), mecobalamin+thioctic acid+calcium dobesilate group (D) (1.0mg/kg+0.2g/kg+1g/kg), mecobalamin+epalrestat+oxybenzene sulphur group (E) (1.0mg/kg+0.1g/kg+1g/kg), mecobalamin+thioctic acid+epalrestat+calcium dobesilate group (F) (1.0mg/kg+0.2g/kg+0.1g/kg+1g/kg).Medicine is mixed with the liquid of mix entreating of debita spissitudo with 0.5%CMC.Na solution, with 1ml/100g gastric infusion once a day, 8 weeks of successive administration.Model group, matched group are irritated stomach with CMC.Na solution.
2. observation index:
2.1 general index observing: dynamic monitoring the weight of animals, tail vein are got blood, blood glucose meter monitoring blood glucose.Per 2～3 weeks are measured once.
2.2 the threshold of pain is measured: the certain position of mechanical presses rat tails and produce rat and shout, measure this pressure size as the mechanical stimulus threshold of pain.Per 2 weeks are measured once.
2.3 sciatic nerve conduction velocity (MNCV) is measured: the rat ventricumbent position of will regaining consciousness is fixed, stimulating electrode places that sciatic nerve spreads out of the position between femoral greater trochanter and the ischial tuberosity, recording electrode places the ankle joint sciatic nerve through the place, and stimulating electrode and recording electrode all adopt needle electrode.Reference electrode is a needle electrode, places subcutaneous between stimulating electrode and the recording electrode, with recording electrode at a distance of 1cm.Stimulate the wide 0.1ins of ripple, 1.2 times of threshold values of stimulus intensity with the pulse square wave.Between per two stimulations at interval more than the 5s.Computer recording excites nerve and begins time of current potential occurring bringing out to recording electrode place muscle, and this time is incubation period.Measure stimulating electrode to the distance between the recording electrode.For the distance/incubation period between people's formula: MNCV (m/s)=stimulating electrode and recording electrode.
3. statistical method: adopt one factor analysis of variance organize between relatively.
4. result:
4.1 influence (seeing Table 1) to STZ rat body weight and blood glucose
Each treated animal body weight does not all have explicitly difference before the modeling, respectively treats yet no significant difference of treated animal body weight during off-test, but has compared significant difference (P＜0.05) with model group.Each modeling treated animal blood glucose does not have the explicitly difference yet after the modeling; In 2 weeks after the modeling, the model group the weight of animals is starkly lower than matched group.Duration of test model group blood glucose is always apparently higher than matched group, and the compound recipe group that contains thioctic acid all shows certain hypoglycemic activity, but is not very outstanding.
The influence of table 1 pair STZ rat body weight and blood glucose (x ± s)
| Group | n | Body weight (g) | Blood glucose (nmol/L) | ||
| On-test | Off-test | On-test | Off-test | ||
| A | 10 | 168.9±23.69 | 176.36±26.39 | 5.64±2.16 | 5.72±1.68 |
| B C D E F | 10 10 10 10 10 | 172.51±21.36 169.58±23.56 173.26±31.67 168.59±26.84 170.95±24.74 | 135.67±16.82 144.45±20.11 148.47±17.47 145.59±18.54 150.38±13.65 | 26.39±3.78 27.38±3.54 27.91±2.67 26.88±2.86 28.54±3.10 | 28.98±3.66 24.84±2.98 23.98±3.48 25.94±3.30 25.81±2.66 |
4.2 influence to the STZ rat tail mechanical stimulus threshold of pain
The 4th week was compared with matched group after the modeling, model group rat mechanical stimulus pain threshold explicitly reduction (P＜0.01), and each administration group all shows certain antagonism (seeing Table 2).
Table 2 rat mechanical stimulus pain threshold situation of change in 8 weeks
| Group | 2w | 4w | 6w | 8w |
| A B C D E F | 12.1±1.1 8.7±2.4 9.3±1.6 9.5±1.3 9.7±2.2 10.1±1.4 | 12.0±1.5 5.3±1.7 7.8±1.3 8.4±1.5 8.3±1.6 9.2±1.7 | 12.2±2.5 4.2±1.9 8.5±1.6 8.9±1.8 8.8±2.3 9.8±1.9 | 12.1±1.7 3.3±1.8 8.6±1.8 9.0±2.2 9.2±2.1 10.1±2.6 |
4.3 influence to STZ rat sciatic nerve MNCV
From two weeks of modeling, model group rat sciatic nerve conduction velocity obviously slows down than matched group, and each administration group then all has explicitly improvement effect (table 3) to this conduct velocity.
The influence of table 3 STZ rat sciatic nerve MNCV
| Group | 2w | 4w | 6w | 8w |
| A B C D E F | 52.62±2.59 43.36±2.02 45.21±2.84 47.39±4.12 46.36±2.13 47.62±3.51 | 53.29±4.10 40.51±2.11 43.55±1.98 47.62±3.02 48.36±2.05 49.23±2.12 | 53.35±2.12 38.64±2.13 46.42±2.64 48.36±2.45 49.33±2.63 51.25±1.95 | 54.36±1.73 37.31±1.87 48.12±2.37 50.16±3.16 51.26±2.63 53.01±1.23 |
Compound recipe mecobalamin+thioctic acid of the present invention in sum, compound recipe mecobalamin+thioctic acid+calcium dobesilate, compound recipe mecobalamin+epalrestat+oxybenzene sulphur, compound recipe mecobalamin+thioctic acid+epalrestat+calcium dobesilate be the effectively reduction of the diabetes-alleviating rat mechanical stimulus threshold of pain and slowing down of nerve conduction velocity all, can effectively improve the nervous symptoms of diabetes rat.Its action intensity is followed successively by F＞E ≈ D＞C.The part compound recipe also has hypoglycemic effect in addition, though act on not obviously, treatment of diabetes has been played positive effect.So compound preparation of the present invention is applicable to the treatment of diabetic neuropathy.
The specific embodiment
Embodiment 1 thioctic acid and mecobalamin tablet
Prescription:
| Component | Consumption |
| Thioctic acid mecobalamin microcrystalline Cellulose CMS-Na micropowder silica gel is made altogether | 1000 of 100g 0.5g 90g 5g 4.5g |
Preparation method:
Thioctic acid, microcrystalline Cellulose are crossed 80 mesh sieves respectively, mix homogeneously, standby; It is an amount of that other gets 50% alcoholic solution, adds mecobalamin and make dissolving, and as binding agent system soft material, 24 mesh sieves are granulated with this solution, 50 ℃ of dryings, and 20 mesh sieve granulate add micropowder silica gel, CMS-Na, adopt suitable punch die compressed tablets behind the mix homogeneously, but.
If carry out coating for above-mentioned tablet, then obtain coated tablet, can be Film coated tablets, enteric coatel tablets etc.
In aforesaid operations, should note lucifuge.
Embodiment 2: compound recipe mecobalamin+thioctic acid+calcium hydrophenyl sulfonate capsule agent
Prescription:
| Component | Consumption |
| Thioctic acid mecobalamin calcium dobesilate starch magnesium stearate is made altogether | 1000 of 100g 0.5g 500g 10g 10g |
Preparation method:
Thioctic acid, calcium dobesilate are all crossed 80 mesh sieves, behind the starch mix homogeneously, standby; It is an amount of that other gets 50% alcoholic solution, adds mecobalamin and make dissolving, and as binding agent system soft material, 24 mesh sieves are granulated with this solution, 50 ℃ of dryings, and 20 mesh sieve granulate add magnesium stearate, mix homogeneously, packing, promptly.
Used capsule shells can be conventional capsule, also can be enteric coated capsule.
Above step should strict lucifuge be handled.
Embodiment 3: lipoic acid compound+epalrestat+calcium dobesilate and mecobalamin chewable tablet
Prescription:
| Component | Consumption |
| The micropowder silica gel of thioctic acid epalrestat calcium dobesilate sorbitol Fructus Citri sinensis powdered flavor is made altogether | 1000 of 100g 50g 500g 500g 30g 20g |
Preparation method:
Thioctic acid, epalrestat, calcium dobesilate are all crossed 80 mesh sieves, and behind the sorbitol mix homogeneously, it is an amount of to get 50% alcoholic solution, and as binding agent system soft material, 24 mesh sieves are granulated, 50 ℃ of dryings, 20 mouthfuls of sieve granulate.Add Fructus Citri sinensis powdered flavor, micropowder glue mix homogeneously, tabletting, promptly.
Embodiment 4: compound recipe mecobalamin+thioctic acid+epalrestat+calcium dobesilate effervescent tablet
Prescription
| Component | Consumption |
| Thioctic acid mecobalamin epalrestat calcium dobesilate citric acid sodium bicarbonate sodium carbonate Fructus Citri sinensis powdered flavor sodium chloride is made altogether | 1000 of 100g 0.5g 50g 500g 500g 400g 150g 15g 15g |
Preparation method:
With adjuvant mix homogeneously such as thioctic acid, epalrestat, calcium dobesilate and citric acid, sodium carbonate, sodium bicarbonate, with the dehydrated alcohol system soft material that is dissolved with mecobalamin, 14 mesh sieves are granulated, 45 ℃ of oven dry, 12 mesh sieve granulate add adjuvants such as Fructus Citri sinensis powdered flavor and sodium chloride, and humidity controls environment, tabletting gets final product.
Embodiment 5: compound recipe mecobalamin+vitamin B12+cobamamide oral cavity disintegration tablet
Prescription
| Component | Consumption |
| Mecobalamin vitamin B12 cobamamide microcrystalline Cellulose xylitol stevioside PPVP flavoring orange essence is made altogether | 0.5g 1000 of 0.5g 0.5g 50g 90g 4.5g 10.5g 3.0g |
Preparation method:
Xylitol, microcrystalline Cellulose are crossed 60 mesh sieves, mix homogeneously, standby; It is an amount of that other gets 50% alcoholic solution, add mecobalamin, vitamin B12, cobamamide and make dissolving, with this solution as binding agent system soft material, 24 mesh sieves are granulated, 50 ℃ of dryings, 20 mesh sieve granulate, with aspartame, flavoring orange essence, PPVP mix homogeneously, tabletting gets final product.
Claims (10)
1. the present invention is a series of pharmaceutical compositions that are used for the treatment of chronic complicating diseases of diabetes, it is characterized in that: by at least two kinds of compositionss that active component forms in mecobalamin, cobamamide, vitamin B12, epalrestat, thioctic acid, the calcium dobesilate.Wherein thioctic acid can replace with D-thioctic acid or L-thioctic acid.
2. the pharmaceutical composition described in the claim 1, it is characterized in that: preferred composition is: mecobalamin+thioctic acid, mecobalamin+thioctic acid+calcium dobesilate, mecobalamin+epalrestat+calcium dobesilate, mecobalamin+thioctic acid+epalrestat+calcium dobesilate, mecobalamin+vitamin B12+cobamamide.
3. the pharmaceutical composition described in the claim 2, it is characterized in that: in its mecobalamin+thioctic acid compositions, mecobalamin unit administration dosage is 0.1～2.0mg, is preferably 0.5mg, the unit administration dosage 10～500mg of thioctic acid is preferably 100mg.
4. the pharmaceutical composition described in the claim 2, it is characterized in that: in its mecobalamin+thioctic acid+phenolsulfonic acid calcium composition, the unit administration dosage of mecobalamin is 0.1～2.0mg, be preferably 0.5mg, the unit administration dosage 10～500mg of thioctic acid, be preferably 100mg, the unit administration dosage of calcium dobesilate is 100～2000mg, is preferably 500mg.
5. the pharmaceutical composition described in the claim 2, it is characterized in that: in its mecobalamin+epalrestat+phenolsulfonic acid calcium composition, the unit administration dosage of mecobalamin is 0.1～2.0mg, be preferably 0.5mg, the unit administration dosage of epalrestat is 10～200mg, be preferably 50mg, the unit administration dosage of calcium dobesilate is 100～2000mg, is preferably 500mg.
6. the pharmaceutical composition described in the claim 2, it is characterized in that: in its mecobalamin+thioctic acid+epalrestat+phenolsulfonic acid calcium composition, the unit administration dosage of mecobalamin is 0.1～2.0mg, be preferably 0.5mg, the unit administration dosage 10～500mg of thioctic acid is preferably 100mg, the unit administration dosage of epalrestat is 10～200mg, be preferably 50mg, the unit administration dosage of calcium dobesilate is 100～2000mg, is preferably 500mg.
7. the pharmaceutical composition described in the claim 2, it is characterized in that: in its mecobalamin+vitamin B12+cobamamide compositions, the unit administration dosage of mecobalamin is 0.1～2.0mg, be preferably 0.5mg, the unit administration dosage of vitamin B12 is 0.005～0.20mg, be preferably 0.5mg, the unit administration dosage that is preferably cobamamide is 0.05～2mg, is preferably 0.25～0.5mg.
8. the pharmaceutical composition described in the claim 1～7, it is characterized in that: each pharmaceutical composition all can be made oral formulations (including but are not limited to tablet, dispersible tablet, effervescent tablet, capsule, soft capsule, granule) with acceptable accessories.
9. the pharmaceutical composition described in the claim 1～8 is characterized in that: be used for the treatment of chronic complicating diseases of diabetes.
10. the pharmaceutical composition described in the claim 9, it is characterized in that: its chronic complicating diseases is a diabetic neuropathy.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100558205A CN101214257A (en) | 2008-01-09 | 2008-01-09 | Medicinal composition for treating diabetes chronic complication and preparation method thereof |
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|---|---|---|---|
| CNA2008100558205A CN101214257A (en) | 2008-01-09 | 2008-01-09 | Medicinal composition for treating diabetes chronic complication and preparation method thereof |
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| CN101214257A true CN101214257A (en) | 2008-07-09 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109528734A (en) * | 2019-01-24 | 2019-03-29 | 华纳时代健康科技（武汉）股份有限公司 | A kind of compound nutritional composition and preparation method thereof |
| CN111084782A (en) * | 2020-01-17 | 2020-05-01 | 龚跃明 | A pharmaceutical composition for treating diabetic complication |
| CN111249300A (en) * | 2020-02-11 | 2020-06-09 | 山东大学 | Application of melatonin combined with Maitake in treating diabetic wound healing disorder |
| CN114028358A (en) * | 2021-12-03 | 2022-02-11 | 锦州福寿堂医药科技有限公司 | Lipoic acid soft capsules for treating diabetes and complications thereof, and preparation method and application thereof |
-
2008
- 2008-01-09 CN CNA2008100558205A patent/CN101214257A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109528734A (en) * | 2019-01-24 | 2019-03-29 | 华纳时代健康科技（武汉）股份有限公司 | A kind of compound nutritional composition and preparation method thereof |
| CN111084782A (en) * | 2020-01-17 | 2020-05-01 | 龚跃明 | A pharmaceutical composition for treating diabetic complication |
| CN111249300A (en) * | 2020-02-11 | 2020-06-09 | 山东大学 | Application of melatonin combined with Maitake in treating diabetic wound healing disorder |
| CN114028358A (en) * | 2021-12-03 | 2022-02-11 | 锦州福寿堂医药科技有限公司 | Lipoic acid soft capsules for treating diabetes and complications thereof, and preparation method and application thereof |
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