CN106110310A - A kind of compound for reducing blood suger containing pioglitazone and preparation method thereof - Google Patents
A kind of compound for reducing blood suger containing pioglitazone and preparation method thereof Download PDFInfo
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- A61K38/46—Hydrolases (3)
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
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- A61K31/33—Heterocyclic compounds
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
Abstract
The present invention relates to a kind of compound for reducing blood suger containing pioglitazone and preparation method thereof, described composition weight proportioning is: pioglitazone 0.05 0.15 parts, acetazolamide 0.5 2.8 parts, vitamin A 1.2 3.4 parts, arabinose 0.4 0.8 parts, 0.6 2.0 parts of folic acid, 0.5 1.5 parts of benzoic acid, taurine 0.3 0.9 parts, acesulfame-K 0.8 1.4 parts, lentinan 0.2 0.6 parts, vitamin B12 0.7 1.0 parts, proline 0.4 0.8 parts, calcium citrate 0.6 1.2 parts, xylitol 0.2 0.8 parts, compound enzyme 0.05 0.08 parts, magnesium stearate 0.9 2.5 parts, carboxymethyl starch sodium 26 parts, binding agent 5 40 parts.The compound for reducing blood suger of the present invention, by adding adjuvant, can make tablet or capsule according to common process, and using method is simple, has good blood sugar lowering diuretic effect according to clinical verification.
Description
Technical field
The present invention relates to diabetic technical field, particularly to a kind of compound for reducing blood suger containing pioglitazone and system thereof
Preparation Method.
Background technology
Along with carrying of our people's growth in the living standard, the change of living habits and social senilization's degree
Height, the prevalence of diabetes is in rapid increase trend, and diabetes are one of modal chronic disease, wherein type 2 diabetes mellitus
Sickness rate more, type 2 diabetes mellitus refers to that the ability producing insulin in the patient not completely loses, the pancreas in the patient having
Island element even produces too much, but the action effect of insulin is poor, and insulin the most in the patient is a kind of shortage relatively, can
To be stimulated the secretion of internal insulin by some oral drugs.But still there are some client need to use insulin to control to the later stage
Treat.Diabetes clinic mainly shows as hyperglycemia, and common sympton has polydipsia, polyuria, polyphagia and becomes thin, if can not get having
The treatment of effect, persistent high blood sugar and long-term metabolic are disorderly etc. may result in body tissue's organ, particularly to eye, kidney, cardiovascular and
Neural infringement and dysfunction thereof and exhaustion, severe patient can cause dehydration, electrolyte disturbance and acid base imbalance etc.
Acute complications, ketoacidosis and Hyperosmotic coma, physiology and psychology to patient all cause harm greatly.As: insulin
Insulin sensitivity is reduced by absolute or relative hyposecretion and target tissue cell, protein, fat, water and electrolyte etc.
Range of metabolic derangement syndrome.Along with the raising of people's living standard, aged tendency of population and the increase of fat incidence rate, glycosuria
Sick sickness rate is in ascendant trend year by year.China is one of diabetes country occurred frequently, whole nation diabetics about 100,000,000, due to
The complication of the parenchymatous organs such as diabetes easy secondary hypertension, atherosclerosis, kidney and retinal microvascular disease, therefore
It has become a kind of popular non-infective disease of serious harm society and family.The most how to reduce blood glucose, control and alleviate sugar
The urine various symptoms that cause of disease are one of problems of paying close attention to the most of modern people.
At present, the treatment of type 2 diabetes mellitus mainly uses Western medicine be administered orally, but the most prominent untoward reaction of these medicines is exactly
Hypoglycemia, and may induction body weight increase so that it is clinical practice is limited, and the organs such as kidney,liver,spleen are brought side effect, currently controls
The Chinese medicine preparation treated there is also many drawbacks, and therapeutic effect is inconspicuous, and onset diabetes rate is climbed the most successively in addition
Rising, existing medicine will be unable to meet future market demand, and we must be to improve preparation stability and bioavailability
Purpose, strengthens the creative fast development controlling type 2 diabetes mellitus.Therefore, for disease Forming Mechanism, find and develop
Safer and more effective newtype drug prevents and controls the PD of type 2 diabetes mellitus have the most great clinical meaning.
Summary of the invention
The present invention provides a kind of compound for reducing blood suger containing pioglitazone and preparation method thereof.
A kind of compound for reducing blood suger containing pioglitazone, described compositions component meter by weight comprises: pioglitazone 0.05-
0.15 part, acetazolamide 0.5-2.8 part, retinol1 .2-3.4 part, folic acid 0.6-2.0 part, benzoic acid 0.5-1.5 part, cattle sulphur
Acid 0.3-0.9 part, acesulfame-K 0.8-1.4 part, lentinan 0.2-0.6 part, vitamin B12 0.7-1.0 part, proline 0.4-
0.8 part, calcium citrate 0.6-1.2 part, xylitol 0.2-0.8 part, compound enzyme 0.05-0.08 part, magnesium stearate 0.9-2.5 part,
Carboxymethyl starch sodium 2-6 part, binding agent 5-40 part.
Further, described binding agent is Hydroxypropylcelliloxe, bonds with Hydroxypropylcelliloxe
Agent, is possible not only to make the mobility of particle of obtained compositions and compressibility all be very significantly improved, and to product
Other index all has no significant effect.
The preparation method of a kind of compound for reducing blood suger containing pioglitazone is:
(1) by pioglitazone, acetazolamide, vitamin, arabinose, folic acid, benzoic acid, taurine, lentinan, dimension
Raw element B12, proline, calcium citrate, xylitol, magnesium stearate, carboxymethyl starch sodium are pulverized, after crossing 120-150 mesh sieve respectively
Standby；
(2) weigh the Hydroxypropylcelliloxe of described composition by weight, be 35-55% with the mass concentration of 3-5 times amount
Ethanol solution mixing, wherein ethanol eliminates by heater means in preparation process, prepared soft material；
(3) weigh the acesulfame-K of described composition by weight, melt with the pure water of 40-45 DEG C of 3-5 times amount, prepare acesulfame potassium
Solution, acesulfame potassium is the most non-hygroscopic, to thermally-stabilised, be resistant to 225 DEG C of high temperature, do not send out with other composition or additive during use
Raw reaction, is not metabolized, does not produce heat, is suitable for diabetics life-time service；
(4) pioglitazone of preparation, acetazolamide, vitamin, Arab in (1) are weighed respectively according to described composition by weight
Sugar, folic acid, benzoic acid, taurine, lentinan, vitamin B12, proline, calcium citrate, xylitol, magnesium stearate, carboxylic first
Prepare medicament mixed powder after the mixing of base Starch Sodium medicated powder, medicament mixed powder is joined in soft material prepared by (2), in adding procedure
Use mechanical agitation to obtain hybrid medicine thick paste, to thick paste adds acesulfame potassium solution prepared by (3), be placed in 35-45 DEG C of baking
It is dried in case so that it is moisture is less than 6%, after pulverizing, crosses 60-80 mesh sieve, pack after adding compound enzyme and seal up for safekeeping, described compound
Enzyme is amylase and dextranase to be mixed to prepare according to the weight ratio of 2:1, and the protein in human body and saccharide can be carried out by it
Effective decomposition, promotes human body homergy, i.e. prepares a kind of compound for reducing blood suger containing pioglitazone.
Further, a kind of compound for reducing blood suger containing pioglitazone adds adjuvant: diluents microcrystalline cellulose 35-60
Part, wetting agent Pulvis Talci 22-36 part, disintegrating agent cross-linked cellulose 12-18 part, by pelletizing, being dried, granulate, sieve, fill,
Polishing, packaging make capsule.
Further, a kind of compound for reducing blood suger containing pioglitazone adds adjuvant: filler dextrin 38-72 part, disintegrate
Agent cross linked polyvinyl pyrrolidone 12-20 part, lubricant micropowder silica gel 18-26 part, by pelletizing, being dried, granulate, mix, press
Sheet, packaging make tablet.
Beneficial effects of the present invention is embodied in: pioglitazone is thiazolidinediones antidiabetic medicine, belongs to insulin and increases
Quick dose, the insulin resistant of peripheral tissues and liver can be reduced, increase the process of the glucose relying on insulin, and reduce glycogen
Output, can improve the insulin sensitivity of Patients with Insulin Resistance, improve the insulin reactivity to cell, and improve body
Interior glucose balance obstacle；Acetazolamide and pioglitazone use in conjunction, can reduce hypoglycemic reaction, it is possible to alleviate the sense of patient
Feel exception and gastrointestinal symptom, moreover it is possible to buffer electrolyte is unbalance, thus plays the effect of diuresis；Arabinose, lentinan, wood
Sugar alcohol synergy shows themselves in that the enzyme of suppression hydrolysis disaccharidase can suppress the blood glucose caused because taking in sucrose to raise, and makes simultaneously
The sucrose not being decomposed in small intestinal is decomposed by the microorganisms in large intestine and produces substantial amounts of organic acid, and this organic acid is to liver
Synthctic fat has inhibitory action, add arabinose in small intestinal to absorb sucrose inhibitory action, thus reduce internal newly
The generation of fat, life-time service can reduce blood glucose；Vitamin A is the antioxidant of a kind of effective capture active oxygen of body,
For preventing lipid peroxidation, prevent cardiovascular disease, tumor, contribute to function of immune system normal；Benzoic acid at human body and
Animal tissue can be combined with the glycine of protein component and detoxify, reduce the side effect in human body of other Western medicine simultaneously；
Taurine, vitamin B12, proline, calcium citrate, folic acid synergy supplement human body when utilizing sugar and aminoacid must
Wanting material, provide body cell growth and the necessary material of breeding simultaneously, taurine can be combined with Insulin receptor INSR, promotes thin
Born of the same parents absorb and utilize glucose, accelerate glycolysis, reduce blood sugar concentration, and vitamin B12, presented in coenzyme, can increase
The utilization rate of folic acid, promotes carbon water composition, fat and the metabolism of protein, and internal desired protein can be carried out by proline
Supplementing, calcium citrate can promote steatolysis after dissolving, keeps health acid-base balance, and folic acid helps the metabolism of protein, also makees
Work for the promotion multiplicaiton factor of lactobacillus casei and other microorganism.The comprehensive onset of above medicine, mastery reaction is fall
Sugar diuresis, does not completely loses for the ability producing insulin in the patient, or the insulin in the patient having even produces
Too much, but the action effect of insulin is poor, and insulin in the patient is the diabetes of a kind of relative deficiency state, promotees simultaneously
Entering body metabolism, strengthen immunologic function, toxic and side effects is little, easy to use, has good clinical expansion effect.
Present composition operation instruction
Indication: type 2 diabetes mellitus
Usage and dosage: oral, each 0.25g, every day 2 times, maximum dose level not above 1.5g or was followed the doctor's advice on 1st.
Points for attention: the patient of this compositions or formulation ingredients allergy is disabled.Enter in strict accordance with the dosage of operation instruction
Row is taken, and this product only just plays the effect of hyperglycemia in the case of excreting insulin in the patient, therefore, is not suitable for
Type 1 diabetes patient or the patient of diabetes ketoacidosis.
Accompanying drawing explanation
Fig. 1 be a kind of compound for reducing blood suger containing pioglitazone of the present invention zoopery in before four groups of rat experiments
After blood glucose average content comparison diagram.
Detailed description of the invention
Embodiment 1:
A kind of compound for reducing blood suger containing pioglitazone, described compositions component meter by weight comprises: pioglitazone 0.05 part,
Acetazolamide 0.5 part, retinol1 .2 part, 0.6 part of folic acid, 0.5 part of benzoic acid, taurine 0.3 part, acesulfame-K 0.8 part, Lentinus Edodes
Polysaccharide 0.2 part, vitamin B12 0.7 part, proline 0.4 part, calcium citrate 0.6 part, xylitol 0.2 part, compound enzyme 0.05 part,
Magnesium stearate 0.9 part, carboxymethyl starch sodium 2 parts, binding agent 5 parts.
Wherein, described binding agent is Hydroxypropylcelliloxe, makees binding agent with Hydroxypropylcelliloxe, no
The mobility of particle of obtained compositions and compressibility only can be made all to be very significantly improved, and other of product is referred to
Mark all has no significant effect.
The preparation method of a kind of compound for reducing blood suger containing pioglitazone is:
(1) by pioglitazone, acetazolamide, vitamin, arabinose, folic acid, benzoic acid, taurine, lentinan, dimension
Raw element B12, proline, calcium citrate, xylitol, magnesium stearate, carboxymethyl starch sodium are pulverized respectively, standby after crossing 120 mesh sieves；
(2) Hydroxypropylcelliloxe of described composition by weight is weighed, with the ethanol that mass concentration is 35% of 3 times amount
Solution mixes, and wherein ethanol is eliminated by heater means in preparation process, prepares soft material；
(3) weigh the acesulfame-K of described composition by weight, melt with the pure water of 40 DEG C of 3 times amount, prepare acesulfame potassium solution,
Acesulfame potassium is the most non-hygroscopic, to thermally-stabilised, is resistant to 225 DEG C of high temperature, does not occurs anti-with other composition or additive during use
Should, it is not metabolized, does not produce heat, be suitable for diabetics life-time service；
(4) pioglitazone of preparation, acetazolamide, vitamin, Arab in (1) are weighed respectively according to described composition by weight
Sugar, folic acid, benzoic acid, taurine, lentinan, vitamin B12, proline, calcium citrate, xylitol, magnesium stearate, carboxylic first
Prepare medicament mixed powder after the mixing of base Starch Sodium medicated powder, medicament mixed powder is joined in soft material prepared by (2), in adding procedure
Use mechanical agitation to obtain hybrid medicine thick paste, to thick paste adds acesulfame potassium solution prepared by (3), be placed in 35 DEG C of baking ovens
Being dried so that it is moisture is less than 6%, cross 60 mesh sieves after pulverizing, pack and seal up for safekeeping after adding compound enzyme, described compound enzyme is to form sediment
Powder enzyme and dextranase are mixed to prepare according to the weight ratio of 2:1, and the protein in human body and saccharide can effectively be divided by it
Solve, promote human body homergy, i.e. prepare a kind of compound for reducing blood suger containing pioglitazone；
(5) give in (4) compound for reducing blood suger of preparing and add adjuvant: diluents microcrystalline cellulose 35 parts, wetting agent Pulvis Talci
22 parts, disintegrating agent cross-linked cellulose 12 parts, by pelletizing, being dried, granulate, sieves, fills, polishes, packs and make capsule.
Embodiment 2:
A kind of compound for reducing blood suger containing pioglitazone, described compositions component meter by weight comprises: pioglitazone 0.10 part,
Acetazolamide 1.65 parts, dehydroretinol .3 part, 1.3 parts of folic acid, 1.0 parts of benzoic acid, taurine 0.6 part, acesulfame-K 1.1 parts, perfume
Mushroom polysaccharide 0.4 part, vitamin B12 0.85 part, proline 0.6 part, calcium citrate 0.9 part, xylitol 0.5 part, compound enzyme
0.065 part, magnesium stearate 1.7 parts, carboxymethyl starch sodium 4 parts, binding agent 22.5 parts.
Wherein, described binding agent is Hydroxypropylcelliloxe, makees binding agent with Hydroxypropylcelliloxe, no
The mobility of particle of obtained compositions and compressibility only can be made all to be very significantly improved, and other of product is referred to
Mark all has no significant effect.
The preparation method of a kind of compound for reducing blood suger containing pioglitazone is:
(1) by pioglitazone, acetazolamide, vitamin, arabinose, folic acid, benzoic acid, taurine, lentinan, dimension
Raw element B12, proline, calcium citrate, xylitol, magnesium stearate, carboxymethyl starch sodium are pulverized respectively, standby after crossing 135 mesh sieves；
(2) Hydroxypropylcelliloxe of described composition by weight is weighed, with the ethanol that mass concentration is 45% of 4 times amount
Solution mixes, and wherein ethanol is eliminated by heater means in preparation process, prepares soft material；
(3) weigh the acesulfame-K of described composition by weight, melt with the pure water of 42.5 DEG C of 4 times amount, prepare acesulfame potassium molten
Liquid, acesulfame potassium is the most non-hygroscopic, to thermally-stabilised, is resistant to 225 DEG C of high temperature, does not occurs with other composition or additive during use
Reaction, is not metabolized, does not produce heat, is suitable for diabetics life-time service；
(4) pioglitazone of preparation, acetazolamide, vitamin, Arab in (1) are weighed respectively according to described composition by weight
Sugar, folic acid, benzoic acid, taurine, lentinan, vitamin B12, proline, calcium citrate, xylitol, magnesium stearate, carboxylic first
Prepare medicament mixed powder after the mixing of base Starch Sodium medicated powder, medicament mixed powder is joined in soft material prepared by (2), in adding procedure
Use mechanical agitation to obtain hybrid medicine thick paste, to thick paste adds acesulfame potassium solution prepared by (3), be placed in 40 DEG C of baking ovens
Being dried so that it is moisture is less than 6%, cross 70 mesh sieves after pulverizing, pack and seal up for safekeeping after adding compound enzyme, described compound enzyme is to form sediment
Powder enzyme and dextranase are mixed to prepare according to the weight ratio of 2:1, and the protein in human body and saccharide can effectively be divided by it
Solve, promote human body homergy, i.e. prepare a kind of compound for reducing blood suger containing pioglitazone；
(5) give in (4) compound for reducing blood suger of preparing and add adjuvant: diluents microcrystalline cellulose 47.5 parts, wetting agent Talcum
29 parts of powder, disintegrating agent cross-linked cellulose 15 parts, by pelletizing, being dried, granulate, sieves, fills, polishes, packs and make capsule.
Embodiment 3:
A kind of compound for reducing blood suger containing pioglitazone, described compositions component meter by weight comprises: pioglitazone 0.15
Part, acetazolamide 2.8 parts, 3-Hydroxyretinol .4 part, 2.0 parts of folic acid, 1.5 parts of benzoic acid, taurine 0.9 part, acesulfame-K 1.4 parts,
Lentinan 0.6 part, vitamin B12 1.0 parts, proline 0.8 part, calcium citrate 1.2 parts, xylitol 0.8 part, compound enzyme
0.08 part, magnesium stearate 2.5 parts, carboxymethyl starch sodium 6 parts, binding agent 40 parts.
Wherein, described binding agent is Hydroxypropylcelliloxe, makees binding agent with Hydroxypropylcelliloxe, no
The mobility of particle of obtained compositions and compressibility only can be made all to be very significantly improved, and other of product is referred to
Mark all has no significant effect.
The preparation method of a kind of compound for reducing blood suger containing pioglitazone is:
(1) by pioglitazone, acetazolamide, vitamin, arabinose, folic acid, benzoic acid, taurine, lentinan, dimension
Raw element B12, proline, calcium citrate, xylitol, magnesium stearate, carboxymethyl starch sodium are pulverized respectively, standby after crossing 150 mesh sieves；
(2) Hydroxypropylcelliloxe of described composition by weight is weighed, with the ethanol that mass concentration is 55% of 5 times amount
Solution mixes, and wherein ethanol is eliminated by heater means in preparation process, prepares soft material；
(3) weigh the acesulfame-K of described composition by weight, melt with the pure water of 45 DEG C of 5 times amount, prepare acesulfame potassium solution,
Acesulfame potassium is the most non-hygroscopic, to thermally-stabilised, is resistant to 225 DEG C of high temperature, does not occurs anti-with other composition or additive during use
Should, it is not metabolized, does not produce heat, be suitable for diabetics life-time service；
(4) pioglitazone of preparation, acetazolamide, vitamin, Arab in (1) are weighed respectively according to described composition by weight
Sugar, folic acid, benzoic acid, taurine, lentinan, vitamin B12, proline, calcium citrate, xylitol, magnesium stearate, carboxylic first
Prepare medicament mixed powder after the mixing of base Starch Sodium medicated powder, medicament mixed powder is joined in soft material prepared by (2), in adding procedure
Use mechanical agitation to obtain hybrid medicine thick paste, to thick paste adds acesulfame potassium solution prepared by (3), be placed in 45 DEG C of baking ovens
Being dried so that it is moisture is less than 6%, cross 80 mesh sieves after pulverizing, pack and seal up for safekeeping after adding compound enzyme, described compound enzyme is to form sediment
Powder enzyme and dextranase are mixed to prepare according to the weight ratio of 2:1, and the protein in human body and saccharide can effectively be divided by it
Solve, promote human body homergy, i.e. prepare a kind of compound for reducing blood suger containing pioglitazone；
(5) give in (4) compound for reducing blood suger of preparing and add adjuvant: 72 parts of filler dextrin, disintegrating agent crosslinked polyethylene ratio
Pyrrolidone 20 parts, lubricant micropowder silica gel 26 parts, by pelletizing, being dried, granulate, mixing, tabletting, packaging make tablet.
The animal effect experiment of the present invention:
1. the foundation of diabetes rat model:
Select male rat 200, body weight 220-250g, after normally feeding one week, be divided into according to body weight randomized blocks
Normal group and model group, wherein Normal group 20, model group 180.Before setting up model, Normal group and model group are equal
Water 24h is can't help in fasting, and model group is injected 2% streptozotocin solution with 60mg/kg dosage disposable celiac and (used before use
The 0.1M citrate buffer solution of PH4.2 is configured to 2% solution), Normal group lumbar injection is with dosage citric acid-sodium citrate
Buffer, takes blood in eye socket after 72h, centrifugal after standing, separates serum, operates according to Glucose estimation kit description,
Measuring detection FBG on semi-automatic biochemical analyzer, reject the too high or too low person of blood glucose, the rat choosing fasting glucose ＞ 11mmol/l makees
For experimental model.
2. rat drug effect control experiment:
A. packet: choose satisfactory diabetes rat 120, is divided into common drug group and invention test group 1, invention
Test group 2, invention test group 3, often group 30, every vital sign and fasting glucose content no significant difference, have comparability.
B. it is administered: use diformin tablet, 0.25mg/kg to the rat of common drug group, uses once every day；Give invention
Test group 1, invention test group 2, invention test group 3 use glue prepared by the embodiment of the present invention 1, embodiment 2, embodiment 3 respectively
Wafer or tablet, 0.18mg/kg, use once every day；Medication is to mix with the pure water of 5 times amount after medicine pulverizing
Rear gavage, continuous gavage 15 days.
C. heavy dose of experiment: after the rat of three groups of invention test group in B is stopped gavage 5 days, with 5 multiple dose gavages 7
My god, observe the active situation of rat during gavage, and do anatomy experiment, check the degree of impairment of major organs.
3. result of the test statistics:
A. find that the rat major organs of heavy dose of gavage is showed no exception through anatomy experiment, hence it is demonstrated that the present invention
Compound for reducing blood suger has no obvious toxic-side effects；
B. for the blood glucose average content before and after four groups of rat experiments as shown in Figure 1.
The compound for reducing blood suger the most of the present invention impact tool compared with common hypoglycemic medicine on blood glucose in diabetic rats
Having notable or pole significant difference, this shows that pharmaceutical composition of the present invention has in terms of improving diabetes glucose, level of sugar
Well effect.
The clinical experiment of the present invention:
1. case is chosen: choose patient 200 example being diagnosed as diabetes, the age 38～72 years old, be randomly divided into matched group,
Treatment group a, treatment group b, treatment group c, often organize 50 people, and each group case, in the aspect such as age, the course of disease there are no significant difference, has
Comparability.
2. criterion: have diabetic symptom, after the meal 2 hours blood glucoses >=11.1mmol/L or fasting glucose >=7.8mmol/
L。
3. Therapeutic Method: all cases, during treating, are required to custom of keeping on a diet, and participate in suitable physical culture forging
Refining.Treatment group a, treatment group b, treatment group c patient take respectively embodiment 1, embodiment 2, the capsule of embodiment 3 preparation or
Tablet, every day 2 times, each 0.25g, takes one month continuously.Matched group takes gliquidone capsule, three times a day, every time
30mg, takes one month continuously.Patient periodically follows up a case by regular visits at special outpatient clinic weekly, carries out clinical observation periodic detection empty stomach
Blood glucose.
4. criterion of therapeutical effect: efficacy assessment standard: the most effective: after treatment, symptom disappears substantially, fasting glucose ＜ 7.0mmol/
L, 2 hours blood glucose ＜ 8.3mmol/L, or blood glucose after the meal decline more than 30% before relatively treating.Glycolated hemoglobin and blood fat (TC,
TG) laboratory indexes full recovery is normal；The most effective: after treatment, symptom is obviously improved, fasting glucose ＜ 8.0mmol/L, 2 is little after the meal
Time blood glucose ＜ 10mmol/L, or blood glucose relatively treat before decline more than 10%.Glycolated hemoglobin and blood fat (TC, TG) laboratory indexes
Relatively make moderate progress before treatment, but do not recover normal；The most invalid: after treatment, symptom is not improved, blood glucose, glycolated hemoglobin and
Blood fat (TC, TG) declines not up to above-mentioned standard.
5. result statistics:
By upper table statistical data it can be seen that diabetes are had very by the compound for reducing blood suger containing pioglitazone prepared by the present invention
Good control effect, total effective rate is 86.0%, and has no obvious toxic and side effects, has good clinical expansion meaning.
Last it is noted that above example is only in order to illustrate technical scheme, it is not intended to limit；Although
With reference to previous embodiment, the present invention is described in detail, it will be understood by those within the art that: it still may be used
So that the technical scheme described in previous embodiment to be modified, or wherein portion of techniques feature is carried out equivalent；And
These amendments or replacement, do not make the essence of appropriate technical solution depart from spirit and the model of embodiment of the present invention technical scheme
Enclose.
Claims (8)
1. the compound for reducing blood suger containing pioglitazone, it is characterised in that described compositions component meter by weight comprises: pyrrole lattice arrange
Ketone 0.05-0.15 part, acetazolamide 0.5-2.8 part, retinol1 .2-3.4 part, arabinose 0.4-0.8 part, folic acid 0.6-
2.0 parts, benzoic acid 0.5-1.5 part, taurine 0.3-0.9 part, acesulfame-K 0.8-1.4 part, lentinan 0.2-0.6 part, dimension raw
Element B12 0.7-1.0 part, proline 0.4-0.8 part, calcium citrate 0.6-1.2 part, xylitol 0.2-0.8 part, compound enzyme 0.05-
0.08 part, magnesium stearate 0.9-2.5 part, carboxymethyl starch sodium 2-6 part, binding agent 5-40 part.
A kind of compound for reducing blood suger containing pioglitazone, it is characterised in that described binding agent is high
Replace hydroxypropyl cellulose.
A kind of compound for reducing blood suger containing pioglitazone, it is characterised in that described compositions
Preparation method is:
(1) by pioglitazone, acetazolamide, vitamin A, arabinose, folic acid, benzoic acid, taurine, lentinan, dimension life
Element B12, proline, calcium citrate, xylitol, magnesium stearate, carboxymethyl starch sodium are pulverized respectively, cross 120-150 mesh sieve standby
With；
(2) weigh the Hydroxypropylcelliloxe of described composition by weight, with ethanol solution, prepare soft material；
(3) weigh the acesulfame-K of described composition by weight, melt with the pure water of 40-45 DEG C of 3-5 times amount, prepare acesulfame potassium molten
Liquid；
(4) according to described composition by weight weigh respectively the pioglitazone of preparation in (1), acetazolamide, vitamin, arabinose,
Folic acid, benzoic acid, taurine, lentinan, vitamin B12, proline, calcium citrate, xylitol, magnesium stearate, carboxymethyl
Prepare medicament mixed powder after the mixing of Starch Sodium medicated powder, medicament mixed powder is joined in soft material prepared by (2), adding procedure makes
Obtain hybrid medicine thick paste by mechanical agitation, to thick paste adds acesulfame potassium solution prepared by (3), be placed in 35-45 DEG C of baking oven
Interior dry so that it is moisture is less than 6%, cross 60-80 mesh sieve after pulverizing, pack after adding compound enzyme and seal up for safekeeping, i.e. prepared a kind of
Compound for reducing blood suger containing pioglitazone.
A kind of compound for reducing blood suger containing pioglitazone, it is characterised in that described ethanol solution is:
The mass concentration of 3-5 times amount is the ethanol solution of 35-55%.
5. a kind of compound for reducing blood suger containing pioglitazone as described in Claims 1-4, it is characterised in that described compositions
Middle addition adjuvant: diluent, wetting agent, disintegrating agent, by pelletizing, being dried, granulate, sieves, fills, polishes, packs and make glue
Wafer.
The capsule that a kind of compound for reducing blood suger containing pioglitazone is prepared as, it is characterised in that institute
The diluent stated is microcrystalline Cellulose, and described wetting agent is Pulvis Talci, and described disintegrating agent is cross-linked cellulose.
7. a kind of compound for reducing blood suger containing pioglitazone as described in Claims 1-4, it is characterised in that described compositions
Middle addition adjuvant: filler, disintegrating agent, lubricant, by pelletizing, being dried, granulate, mixing, tabletting, packaging make tablet.
The tablet that a kind of compound for reducing blood suger containing pioglitazone is prepared as, it is characterised in that described
Described filler be dextrin, described disintegrating agent is cross linked polyvinyl pyrrolidone, and described lubricant is micropowder silica gel.
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Application publication date: 20161116 |