CN108079000A - A kind of pharmaceutical composition for treating diabetes and preparation method thereof - Google Patents
A kind of pharmaceutical composition for treating diabetes and preparation method thereof Download PDFInfo
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- CN108079000A CN108079000A CN201810103838.1A CN201810103838A CN108079000A CN 108079000 A CN108079000 A CN 108079000A CN 201810103838 A CN201810103838 A CN 201810103838A CN 108079000 A CN108079000 A CN 108079000A
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- pharmaceutical composition
- diabetes
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Classifications
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- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
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- 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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- A61K31/435—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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A—HUMAN NECESSITIES
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A—HUMAN NECESSITIES
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Abstract
The present invention relates to field of pharmaceutical preparations, specifically disclose a kind of pharmaceutical composition for treating diabetes and preparation method thereof, include the raw material of following parts by weight：52 56 parts of gliquidone, 25 29 parts of pyrrolo- quinoline quinone, support Gree too 13 16 parts of hydrazone, 35 parts of cosolvent, 12 parts of disintegrant, 24 parts of adhesive, 13 parts of lubricant, 12 parts of suspending agent, 0.7 1.1 parts of antioxidant, 0.4 0.8 parts of thickener.The pharmaceutical composition of the present invention is safe and effective at hypoglycemic aspect, and has the advantages that Small side effects.
Description
Technical field
The present invention relates to treating diabetes technical fields, and in particular to a kind of pharmaceutical composition and its system for treating diabetes
Preparation Method.
Background technology
Diabetes are the second killers in modern diseases, and cancer is only second to the harm of human body.In fact, diabetes are in itself
Not fearful, fearful is the complication of diabetes, the harm that diabetes are brought, the nearly all complication from it.In China
In diabetic, complicated hypertension person up to 12,000,000, and cerebral apoplexy person 5,000,000, coronary disease patient 6,000,000, the person of losing the sight of both eyes 45
Ten thousand, uremia person 500,000.
Diabetes be a kind of complex disease because syndrome, be the hormone due to internal insulin deficit or antagonism insulin
Increase or cannot bring into normal play in target cell glucose caused by physiological action, protein and lipid-metabolism of insulin is disorderly
A kind of random syndrome.It is characterized in that there is typical case when concentration of glucose rise and glucose in urine, blood glucose extremely are excessively high in blood circulation
" three-many-one-little " symptom, i.e., it is more eat, diuresis, more foods and weight loss, and with fatigue and weak.Ketosis acid can occur for severe patient
Poisoning, hypertonicity diabetic coma, and easily merge multi-infection.With the extension of the course of disease, metabolic disorder can cause eye, kidney,
The chronic disease of the histoorgans such as nerve, blood vessel and heart.If heart disease, brain occur for treatment that cannot be timely, appropriate
Vascular lesion, renal failure, lose the sight of both eyes, lower limbs necrosis situations such as, become the main reason for disabling, is lethal.
Western medicine is mostly using insulin sensitivity enhancer class drug for oral administration temporarily, and pressed down with sulfonylureas (SU) class drug at present
It is made as more.
In Chinese patent literature " (application number：201610175810.X) " disclose a kind for the treatment of sugar containing gliquidone
Pharmaceutical composition of disease and preparation method thereof is urinated, the bulk pharmaceutical chemicals that it includes following weight form：Gliquidone 15-45
Part, 4000-8000 parts of dill seedling, 4000-8000 parts of the indocalamus base of a fruit, 4000-8000 parts of peach gum, 4000-8000 parts of pilea mongolica.
The pharmaceutical composition of the present invention can add in injection volume some pharmaceutically acceptable auxiliary materials individually or as needed, can be with
The pharmaceutical preparation is prepared using galenic pharmacy routine techniques, such as mixes pharmaceutically active substance with pharmaceutically acceptable auxiliary material.This hair
Bright to be suitable for that unsatisfied light, the moderate Non-Insulin Dependent Diabetes Mellitus of diet control curative effect is applied alone, patient's B cell has one
Fixed excreting insulin work(β cell energy, and without serious complication.But lack for insulin-dependent diabetes mellitus people and treat
Effect, although simultaneously as the adverse reaction of gliquidone can be mitigated by adding in excessive Chinese herbal medicine, so as to fulfill attenuation synergistic
Purpose still, on the other hand but alleviates gliquidone treat diabetes the effect of, reduces gliquidone and control diabetes
Effect.
In Chinese patent literature " (application number：201010131333.X) " disclose the Chinese and Western medicine combination containing gliquidone
Object is made of gliquidone and Chinese medical extract with weight ratio 1: 102, and wherein the Chinese medical extract is made in following manner
Into：By weight by 10 parts of Radix Rehmanniae, 10 parts of the fleece-flower root, 5 parts of Rhizoma Atractylodis Macrocephalae, 5 parts of Radix Astragali, 8 parts of radix scrophulariae, 10 parts of hairyvein agrimony, 8 parts of mulberry leaf,
It adds water to cook, filters, be concentrated into thick paste, it is dry.The composition for the treatment diabetes prepared, although being controlled in Chinese medicine and Western medicine
It is centainly promoted in terms of the synergistic effect for treating diabetes, but compared with simple western medicine scheme, still remains and control
It treats that the cycle is big, slowly effect, and equally exists the situation that Chinese medicine addition causes curative effect to decline.
And in Chinese patent literature " (application number：200410072331.2) " disclose a kind of pharmaceutical composition and its making
Application in standby treatment type II diabetes drug, said composition is by gliquidone and taurine and its pharmaceutical salts and pharmaceutically
Acceptable carrier composition, wherein gliquidone dosage are
10mg-180mg, taurine and its pharmaceutical salts dosage are 0.5g-10g.The diabetes medicament by gliquidone and
Taurine cooperates, the effect of on the one hand can improving gliquidone, and the gliquidone of same dose is used alone
When, blood sugar reducing function becomes apparent from, meanwhile, the addition of taurine can reduce side effect with gliquidone.But it remains as follows
Problem：(1) compatibility of gliquidone and taurine is weaker, and then influences therapeutic effect and the side effect of the drug, and this
The measure of hydrotropy is not taken in invention for the two weaker problem of compatibility；(2) although Taurine is reducing gliquidone side effect
Aspect has certain effect, but the effect in terms of same gliquidone carries out co-action for treating diabetes is insufficient.
Based on this, it is necessary to a kind of pharmaceutical composition for treating diabetes and preparation method thereof is provided, to solve existing skill
Problem present in art.
The content of the invention
Pharmaceutical composition it is an object of the invention to provide treatment diabetes and preparation method thereof, to solve above-mentioned background
The problem of being proposed in technology.
To achieve the above object, the present invention provides following technical solution：
A kind of pharmaceutical composition for treating diabetes includes the raw material of following parts by weight：
52-56 parts of gliquidone, 25-29 parts of pyrrolo- quinoline quinone, too hydrazone 13-16 parts of Gree of support, 3-5 parts of cosolvent, disintegration
1-2 parts of agent, 2-4 parts of adhesive, 1-3 parts of lubricant, 1-2 parts of suspending agent, 0.7-1.1 parts of antioxidant, 0.4-0.8 parts of thickener.
Preferably, a kind of pharmaceutical composition for treating diabetes, include the raw material of following parts by weight：
54 parts of gliquidone, 27 parts of pyrrolo- quinoline quinone, support Gree too 14.5 parts of hydrazone, 4 parts of cosolvent, 1.5 parts of disintegrant, viscous
3 parts of mixture, 2 parts of lubricant, 1.5 parts of suspending agent, 0.9 part of antioxidant, 0.6 part of thickener.
Preferably, the cosolvent is selected from sodium salicylate or sodium acetate.
Preferably, it is 2-4 that the disintegrant, which is selected from mass ratio,:1 calcium carbonate and the mixture of calcium carboxymethylcellulose.
Preferably, the one kind of described adhesive in Arabic gum, polyvinylpyrrolidone or alphalise starch.
Preferably, the one kind of the lubricant in magnesium stearate, talcum powder or Macrogol 6000.
Preferably, the suspending agent is selected from ethylhydroxyethylcellulose, polyoxyethylene alcohol, cellulose acetate O-phthalic
One or more combinations in acid esters.
Preferably, the antioxidant is tert-butyl tert-butyl ether；The thickener is mosanom, carboxymethyl cellulose
Element, polyethylene glycol are according to mass ratio 1：2：The mixture of 3 compositions.
Preferably, the mass ratio of the cosolvent, lubricant, disintegrant, suspending agent, thickener substance is (6-8)：
(4-6)：(3-4)：(2-4)：1.
The present invention also provides a kind of preparation methods for the pharmaceutical composition for treating diabetes, comprise the following steps：
Step 1：Each raw material is weighed according to regulation number；
Step 2：It is added in after disintegrant, cosolvent, lubricant, suspending agent, antioxidant are mixed in dispersion machine, with 140-
The rotating speed of 180rpm disperses 20-30min；
Step 3：Addition gliquidone, pyrrolo- quinoline quinone, support Gree too hydrazone in mixed solution into step 2, and with
The rotating speed stirring 40-60min of 220-260rpm, until all dissolvings；
Step 4：Thickener is first added in mixed solution into step 3,6-8min is stirred with the rotating speed of 190-210rpm,
Then adhesive is added, is stirred for 3-5min；
Step 5：Mixed solution made from step 4 is subjected to cooling processing, stirs to crystallization and completes in cooling, Ran Houyang
Brilliant, suction filtration, washing, the dry pharmaceutical composition to get the treatment diabetes.
Compared with prior art, the present invention has following advantageous effect：
(1) a kind of pharmaceutical composition for treating diabetes of the invention is arranged by adding in insulin sensitivity enhancer lattice
Quinoline ketone increases the effect to insulin receptor, adds the sensibility of the insulin of muscle and adipose tissue, so as to reduce glycogen
Former generation, so as to have the function that reduce blood glucose, but as administration time extends, islet cells receptor is under its sensibility
Drop generates drug resistance, and so as to increase pharmaceutical quantities so as to generate side effect, and the present invention is improved by adding in insulin resistance
The sensibility that agent pyrrolo- quinoline quinone and insulin sensitizer support Gree too hydrazone improve islet cells receptor declines problem, and passes through it
With the synergistic effect of gliquidone, the effect of further enhancing the treatment diabetes of pharmaceutical composition, meanwhile, reduce lattice row quinoline
The side effect of ketone.
(2) agent for amelioration of insulin resistance pyrrolo- quinoline quinone of the invention can enhance insulin sensitivity and improve insulin
Resistance of the target organ to insulin, and then improve the effect of gliquidone reduction blood glucose；And add in insulin sensitizer support Gree
Too hydrazone can act synergistically with gliquidone, reduce blood glucose jointly, so as to achieve the purpose that treat diabetes, while again can be with
Inhibit the side effect of gliquidone.
(3) gliquidone, pyrrolo- quinoline quinone, support Gree too three kinds of substances of hydrazone are mutually dissolved in one by the present invention by cosolvent
It rises, increases drug solubility by the disintegrant of addition, and cosolvent cooperates with disintegrant, and carry out the proportioning of science
Maximum solubility can be reached, the suspending agent of addition can be such that drug is effectively disperseed, further play and fill
Divide immixture, the lubricant of addition reduces the resistance that drug combines, and the addition of thickener and adhesive can increase drug
Concentration and convenient for crystallization, makes drug be chronically at stable state, keeps drug effect by the antioxidant of addition；The present invention is by collapsing
Agent, cosolvent, lubricant, suspending agent, the mass ratio of antioxidant are solved, to reach optimal dissolution rate and therapeutic effect.
(4) preparation method of the invention is simple, it is easy to accomplish, suitable for industrialized production.
Specific embodiment
The following examples will make the present invention more specifically to explain, but the present invention is not limited only to these implementations
Example, these similary embodiments are not also limit the invention in any way.
Embodiment 1：
A kind of pharmaceutical composition for treating diabetes of the present embodiment includes the raw material of following parts by weight：
54 parts of gliquidone, 27 parts of pyrrolo- quinoline quinone, support Gree too 14.5 parts of hydrazone, 4 parts of cosolvent, 1.5 parts of disintegrant, viscous
3 parts of mixture, 2 parts of lubricant, 1.5 parts of suspending agent, 0.9 part of antioxidant, 0.6 part of thickener.
The cosolvent of the present embodiment is selected from sodium salicylate.
The mass ratio that is selected from of the present embodiment is 2:1 calcium carbonate and the mixture of calcium carboxymethylcellulose.
The adhesive of the present embodiment is selected from polyvinylpyrrolidone.
The lubricant of the present embodiment is selected from Macrogol 6000.
The suspending agent of the present embodiment is selected from cellulose acetate phthalate.
The antioxidant of the present embodiment is tert-butyl tert-butyl ether；The thickener for mosanom, carboxymethyl cellulose,
Polyethylene glycol is according to mass ratio 1：2：The mixture of 3 compositions.
The cosolvent, lubricant, disintegrant, suspending agent, the mass ratio of thickener substance of the present embodiment are 7：5：3.5：3：
1。
The present invention also provides a kind of preparation methods for the pharmaceutical composition for treating diabetes, comprise the following steps：
Step 1：Each raw material is weighed according to regulation number；
Step 2：It is added in after disintegrant, cosolvent, lubricant, suspending agent, antioxidant are mixed in dispersion machine, with 140rpm
Rotating speed disperse 20min；
Step 3：Addition gliquidone, pyrrolo- quinoline quinone, support Gree too hydrazone in mixed solution into step 2, and with
The rotating speed stirring 40min of 220rpm, until all dissolvings；
Step 4：Thickener is first added in mixed solution into step 3,6min, Ran Houzai are stirred with the rotating speed of 190pm
Adhesive is added in, is stirred for 3min；
Step 5：Mixed solution made from step 4 is subjected to cooling processing, stirs to crystallization and completes in cooling, Ran Houyang
Brilliant, suction filtration, washing, the dry pharmaceutical composition to get the treatment diabetes.
Embodiment 2：
A kind of pharmaceutical composition for treating diabetes of the present embodiment includes the raw material of following parts by weight：
56 parts of gliquidone, 29 parts of pyrrolo- quinoline quinone, support Gree too 16 parts of hydrazone, 5 parts of cosolvent, 2 parts of disintegrant, adhesive
4 parts, 3 parts of lubricant, 2 parts of suspending agent, 1.1 parts of antioxidant, 0.8 part of thickener.
The cosolvent of the present embodiment is selected from sodium acetate.
It is 4 that the disintegrant of the present embodiment, which is selected from mass ratio,:1 calcium carbonate and the mixture of calcium carboxymethylcellulose.
The adhesive of the present embodiment is selected from Arabic gum.
The lubricant of the present embodiment is selected from magnesium stearate.
The suspending agent of the present embodiment is selected from ethylhydroxyethylcellulose.
The antioxidant of the present embodiment is tert-butyl tert-butyl ether；The thickener for mosanom, carboxymethyl cellulose,
Polyethylene glycol is according to mass ratio 1：2：The mixture of 3 compositions.
The cosolvent, lubricant, disintegrant, suspending agent, the mass ratio of thickener substance of the present embodiment are 7：5：3：3：1.
A kind of preparation method of pharmaceutical composition for treating diabetes of the present embodiment is the same as embodiment 1.
Embodiment 3：
A kind of pharmaceutical composition for treating diabetes of the present embodiment includes the raw material of following parts by weight：
54 parts of gliquidone, 27 parts of pyrrolo- quinoline quinone, support Gree too 14.5 parts of hydrazone, 4 parts of cosolvent, 1.5 parts of disintegrant, viscous
3 parts of mixture, 2 parts of lubricant, 1.5 parts of suspending agent, 0.9 part of antioxidant, 0.6 part of thickener.
The cosolvent of the present embodiment is selected from sodium acetate.
The mass ratio that is selected from of the present embodiment is 3:1 calcium carbonate and the mixture of calcium carboxymethylcellulose.
The adhesive of the present embodiment is selected from polyvinylpyrrolidone.
The lubricant of the present embodiment is selected from talcum powder.
The suspending agent of the present embodiment is selected from polyoxyethylene alcohol.
The antioxidant of the present embodiment is tert-butyl tert-butyl ether；The thickener for mosanom, carboxymethyl cellulose,
Polyethylene glycol is according to mass ratio 1：2：The mixture of 3 compositions.
The cosolvent, lubricant, disintegrant, suspending agent, the mass ratio of thickener substance of the present embodiment are 7：5：2：3：1.
A kind of preparation method of pharmaceutical composition for treating diabetes of the present embodiment is the same as embodiment 1.
Embodiment 4：
A kind of pharmaceutical composition for treating diabetes of the present embodiment includes the raw material of following parts by weight：
53.5 parts of gliquidone, 26.5 parts of pyrrolo- quinoline quinone, support Gree too 15.5 parts of hydrazone, 4.5 parts of cosolvent, disintegrant
1.5 parts, 2.5 parts of adhesive, 2.5 parts of lubricant, 1.5 parts of suspending agent, 0.8 part of antioxidant, 0.7 part of thickener.
The cosolvent of the present embodiment is selected from sodium salicylate.
It is 2.5 that the disintegrant of the present embodiment, which is selected from mass ratio,:1 calcium carbonate and the mixture of calcium carboxymethylcellulose.
The adhesive of the present embodiment is selected from alphalise starch.
The lubricant of the present embodiment is selected from Macrogol 6000.
The suspending agent of the present embodiment is selected from polyoxyethylene alcohol.
The antioxidant of the present embodiment is tert-butyl tert-butyl ether；The thickener for mosanom, carboxymethyl cellulose,
Polyethylene glycol is according to mass ratio 1：2：The mixture of 3 compositions.
The cosolvent, lubricant, disintegrant, suspending agent, the mass ratio of thickener substance of the present embodiment are 6：4：3：2：1.
A kind of preparation method of pharmaceutical composition for treating diabetes of the present embodiment is the same as embodiment 1.
Embodiment 5：
A kind of pharmaceutical composition for treating diabetes of the present embodiment includes the raw material of following parts by weight：
55.5 parts of gliquidone, 27.5 parts of pyrrolo- quinoline quinone, support Gree too 15 parts of hydrazone, 4.5 parts of cosolvent, 2 parts of disintegrant,
2 parts of adhesive, 2.5 parts of lubricant, 1 part of suspending agent, 1 part of antioxidant, 0.5 part of thickener.
The cosolvent of the present embodiment is selected from sodium acetate.
The mass ratio that is selected from of the present embodiment is 3.5:1 calcium carbonate and the mixture of calcium carboxymethylcellulose.
The adhesive of the present embodiment is selected from polyvinylpyrrolidone.
The lubricant of the present embodiment is selected from talcum powder.
The suspending agent of the present embodiment is selected from polyoxyethylene alcohol.
The antioxidant of the present embodiment is tert-butyl tert-butyl ether；The thickener for mosanom, carboxymethyl cellulose,
Polyethylene glycol is according to mass ratio 1：2：The mixture of 3 compositions.
The cosolvent, lubricant, disintegrant, suspending agent, the mass ratio of thickener substance of the present embodiment are 8：6：4：4：1.
A kind of preparation method of pharmaceutical composition for treating diabetes of the present embodiment is the same as embodiment 1.
Comparative example 1：
It is essentially identical with the raw material and preparation process of embodiment 3, have only unlike：
50 parts of gliquidone, 23 parts of pyrrolo- quinoline quinone, support Gree too 11 parts of hydrazone, 2 parts of cosolvent, 0.9 part of disintegrant, bonding
1.8 parts of agent, 0.8 part of lubricant, 0.8 part of suspending agent, 0.6 part of antioxidant, 0.3 part of thickener.
Comparative example 2：
It is essentially identical with the raw material and preparation process of embodiment 3, have only unlike：
58 parts of gliquidone, 31 parts of pyrrolo- quinoline quinone, support Gree too 18 parts of hydrazone, 6 parts of cosolvent, 3 parts of disintegrant, adhesive
5 parts, 4 parts of lubricant, 2.5 parts of suspending agent, 1.2 parts of antioxidant, 0.9 part of thickener.
Comparative example 3：
It is essentially identical with the material and preparation process of embodiment 3, have only unlike：
48 parts of gliquidone, 21 parts of pyrrolo- quinoline quinone, support Gree too 10 parts of hydrazone, 1 part of cosolvent, 0.8 part of disintegrant, bonding
1.6 parts of agent, 0.7 part of lubricant, 0.7 part of suspending agent, 0.5 part of antioxidant, 0.2 part of thickener.
Comparative example 4：
It is essentially identical with the material and preparation process of embodiment 3, have only unlike：
60 parts of gliquidone, 33 parts of pyrrolo- quinoline quinone, support Gree too 20 parts of hydrazone, 7.5 parts of cosolvent, 4 parts of disintegrant, bonding
6 parts of agent, 5 parts of lubricant, 3.5 parts of suspending agent, 1.3 parts of antioxidant, 1 part of thickener.
Comparative example 5：
Using Chinese patent literature " (application number：201610175810.X) " prepared by raw material disclosed in embodiment 1 and method
The pharmaceutical composition for controlling diabetes.
Comparative example 6：
Using Chinese patent literature " (application number：201010131333.X) " prepared by raw material disclosed in embodiment 1 and method
The pharmaceutical composition for controlling diabetes.
Comparative example 7：
Using Chinese patent literature " (application number：200410072331.2) " prepared by raw material disclosed in embodiment 1 and method
The pharmaceutical composition for controlling diabetes.
Comparative example 8：
A kind of pharmaceutical composition for treating diabetes, as different from Example 3, which eliminates pyrrolo- quinoline
Quinone, other conditions are constant.
Comparative example 9：
A kind of pharmaceutical composition for treating diabetes, as different from Example 3, the comparative example eliminate support Gree too
Hydrazone, other conditions are constant.
Test example 1：
1st, test equipment
Automatic clinical chemistry analyzer is U.S.'s BECKMAN Products, Onetouch Ultra fast blood glucose meters, disposable
Blood sugar test paper is Johnson ＆ Johnson of U.S. product.KZ4-GC-2016 γ radiation immunity arithmometers are Ke Lege Giovannis (Shanghai) analytical instrument
Co., Ltd's new product, iMark microplate reader are U.S.'s Bio-rad products.
2nd, method
The preparation of diabetes rat animal model
Rat is randomly divided into high sugared model group (n=500), blank control group (n=30), high sugar model group is by daily
(alloxan is damaged cell DNA, and activates two phosphorus 100mg/kg intraperitoneal injections alloxan by destroying insulin β cells
The activity of adenosine monophosphate Ribosome biogenesis enzyme declines cozymase content, ultimately results in insulin deficit, make metabolic disorder, blood glucose liter
It is high.), after continuous raising 4 weeks, by America Diabetes complication model association (AMDCC) proposed standard, when fasting 6 is small：Morning 7
Point takes blood point at 13 points at noon：An angular vein peripheral blood about 0.4ml is taken to measure after anesthesia.It is required that：Blood glucose (Glu)>
11.1mmol/l is considered as modeling success, shares 432 modeling successes.
3rd, grouping and administration
Grouping and administration：420 successful rats of modeling are chosen, are divided into 14 groups, every group 30, and feeding embodiment respectively
The pharmaceutical composition of 1-5 and the diabetes in comparative example 1-9, blank control group are raised with normal diet, continuous raising 13 weeks.
4th, result of the test：As shown in table 1.
Table 1：Hypoglycemic effect comparative experiments result
As shown in Table 1, the significant blood sugar reducing function of pharmaceutical composition for the treatment of diabetes produced by the present invention, and be substantially better than
Pharmaceutical composition made from comparison row 1-9.
Test example 2：
It is clinical efficacy to diabetic that this test example, which is directed to,
1st, object and method：
(1) case standard is included：Doctor trained in Western medicine is diagnosed as glycosuria patient, and the age is between 40-65 Sui.It is through diet to include case
Blood glucose accepts 60 impaired glucose tolerance patients for medical treatment altogether still in abnormal ranges person after adding movement intervention, is divided into 12 groups, and feeding is implemented respectively
The pharmaceutical composition for the treatment of diabetes obtained in example 1-5 and comparative example 1-9, every time 1 bag of (every bag of 5g.), 3 times a day, 2
The moon is as a treatment course.
(2) MAIN OUTCOME MEASURES：Fasting blood-glucose (FPG), glycosylated hemoglobin (HbA1C), plasma insulin (FINS).
2nd, efficacy evaluation：
(1) control：Blood glucose and fasting blood-glucose recover normal when postprandial 2；
(2) effectively：Blood glucose or fasting blood-glucose reduce when postprandial 2, but do not recover normal；
(3) it is invalid：Blood glucose and fasting blood-glucose are without improvement or rise when postprandial 2.
3rd, clinical observation result
(1) comparison of pretherapy and post-treatment FPG, 2hPG, FINS, as shown in table 2：
Table 2：The experimental result of pretherapy and post-treatment FPG, 2hPG, FINS
As shown in Table 2, using the pharmaceutical composition of 1-5 of the embodiment of the present invention better than comparative example 1-9, and using embodiment 1-
5 medicine composite for curing is after 2 months, the pretherapy and post-treatment significant difference of FPG, 2hPG, illustrates the drug of the present invention and has preferably
Reduce the effect of empty stomach and postprandial hyperglycemia；Meanwhile significant difference before and after Fasting insulin level, illustrate medicine group of the invention
The effect of insulin sensitivity can be improved by closing object.
Test example 3:
In order to prove gliquidone exclusive use and be utilized in conjunction with the effect in treatment diabetes with pyrrolo- quinoline quinone, point
Pharmaceutical composition made from pharmaceutical composition made from other Example 3 and comparative example 9 is tested.
The male mouse of 14-19 week old is divided into 2 groups, every group 10, take respectively pharmaceutical composition made from embodiment 3 and
Pharmaceutical composition made from comparative example 9, feeding takes blood after 14 days from tail vein, using a kind of commercially available reagent box with enzyme process decibel
Measure plasma glucose and HbA1.Test result is as shown in table 3：
3 performance test data of table
As can be seen from Table 3, compared with individually taking gliquidone, gliquidone is taken very with combining for pyrrolo- quinoline quinone
Significantly reduce the concentration of blood-glucose and HbA1.
Test example 4：
In order to prove that the pharmaceutical composition of the treatment diabetes of the present invention has the side effect for inhibiting gliquidone, take respectively
Pharmaceutical composition made from pharmaceutical composition made from embodiment 3 and comparative example 8 is tested.
Whole subjects are divided into two groups in this experiment, take pharmaceutical composition made from embodiment 3 respectively and comparative example 8 is made
The pharmaceutical composition obtained, and pretherapy and post-treatment safety indexes are detected, it turns out that taking the pharmaceutical composition of embodiment 3
Subject have no adverse reaction, and there is enteron aisle adverse reaction in the pharmaceutical composition for taking comparative example 8, and specific test result is shown in
Table 4：
4 the performance test results of table
| Group | Number of cases | Nausea | Vomiting | Abdominal distension | Abdominal pain | Incidence (%) |
| Embodiment 3 | 35 | 1 | 0 | 0 | 0 | 2.9 |
| Comparative example 8 | 35 | 4 | 3 | 4 | 2 | 37.1 |
By table 4 it is recognised that the present invention combines support Gree too hydrazone with gliquidone, caused to avoid gliquidone
Common gastrointestinal side effect, and improve to the therapeutic effects of diabetes, so as to which the pharmaceutical composition for illustrating the present invention exists
Hypoglycemic aspect is safe and effective, and has the advantages that Small side effects.
In conclusion a kind of pharmaceutical composition for treating diabetes of the present invention, is enhanced by adding in insulin sensitivity
Agent gliquidone increases the effect to insulin receptor, adds the sensibility of the insulin of muscle and adipose tissue, so as to subtract
The generation of few hepatic glycogen, so as to have the function that reduce blood glucose, but as administration time extends, islet cells receptor is quick to its
Perception declines, and generates drug resistance, so as to must increase pharmaceutical quantities and and generate side effect, and the present invention is supported by adding in insulin
The sensibility that anti-improver pyrrolo- quinoline quinone and insulin sensitizer support Gree too hydrazone improve islet cells receptor declines problem, and
By its synergistic effect with gliquidone, the effect of further enhancing the treatment diabetes of pharmaceutical composition, meanwhile, it reduces
The side effect of gliquidone.
It is obvious to a person skilled in the art that the invention is not restricted to the details of above-mentioned exemplary embodiment, Er Qie
In the case of without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Profit requirement rather than above description limit, it is intended that all by what is fallen within the meaning and scope of the equivalent requirements of the claims
Variation is included within the present invention.
Moreover, it will be appreciated that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
Using specification as an entirety, the technical solutions in each embodiment can also be properly combined, forms those skilled in the art
It is appreciated that other embodiment.
Claims (10)
1. a kind of pharmaceutical composition for treating diabetes, which is characterized in that include the raw material of following parts by weight：
52-56 parts of gliquidone, 25-29 parts of pyrrolo- quinoline quinone, too hydrazone 13-16 parts of Gree of support, 3-5 parts of cosolvent, disintegrant 1-2
Part, 2-4 parts of adhesive, 1-3 parts of lubricant, 1-2 parts of suspending agent, 0.7-1.1 parts of antioxidant, 0.4-0.8 parts of thickener.
2. the pharmaceutical composition for the treatment of diabetes according to claim 1, which is characterized in that include the original of following parts by weight
Material：
54 parts of gliquidone, 27 parts of pyrrolo- quinoline quinone, support Gree too 14.5 parts of hydrazone, 4 parts of cosolvent, 1.5 parts of disintegrant, adhesive
3 parts, 2 parts of lubricant, 1.5 parts of suspending agent, 0.9 part of antioxidant, 0.6 part of thickener.
3. the pharmaceutical composition for the treatment of diabetes according to claim 1, which is characterized in that the cosolvent is selected from bigcatkin willow
Sour sodium or sodium acetate.
4. the pharmaceutical composition for the treatment of diabetes according to claim 1, which is characterized in that the disintegrant is selected from quality
Than for 2-4:1 calcium carbonate and the mixture of calcium carboxymethylcellulose.
5. the pharmaceutical composition for the treatment of diabetes according to claim 1, which is characterized in that described adhesive is selected from me
One kind in primary glue, polyvinylpyrrolidone or alphalise starch.
6. the pharmaceutical composition for the treatment of diabetes according to claim 1, which is characterized in that the lubricant is selected from tristearin
One kind in sour magnesium, talcum powder or Macrogol 6000.
7. the pharmaceutical composition for the treatment of diabetes according to claim 1, which is characterized in that the suspending agent is selected from ethyl
One or more combinations in hydroxyethyl cellulose, polyoxyethylene alcohol, cellulose acetate phthalate.
8. the pharmaceutical composition for the treatment of diabetes according to claim 1, which is characterized in that the antioxidant is to hydroxyl
Tertiary butyl anisole；The thickener is mosanom, carboxymethyl cellulose, polyethylene glycol are according to mass ratio 1：2：3 compositions mix
Close object.
9. it is according to claim 1 treatment diabetes pharmaceutical composition, which is characterized in that the cosolvent, lubricant,
Disintegrant, suspending agent, the mass ratio of thickener substance are (6-8)：(4-6)：(3-4)：(2-4)：1.
10. a kind of preparation method for preparing the pharmaceutical composition such as claim 1-9 any one of them treatment diabetes, special
Sign is, comprises the following steps：
Step 1：Each raw material is weighed according to regulation number；
Step 2：It is added in after disintegrant, cosolvent, lubricant, suspending agent, antioxidant are mixed in dispersion machine, with 140-180rpm
Rotating speed disperse 20-30min；
Step 3：Gliquidone, pyrrolo- quinoline quinone, support Gree too hydrazone, and with 220- are added in mixed solution into step 2
The rotating speed stirring 40-60min of 260rpm, until all dissolvings；
Step 4：Thickener is first added in mixed solution into step 3,6-8min is stirred with the rotating speed of 190-210rpm, then
Adhesive is added, is stirred for 3-5min；
Step 5：Mixed solution made from step 4 is subjected to cooling processing, while cooling while stir to crystallization complete, then growing the grain,
It filters, wash, the dry pharmaceutical composition to get the treatment diabetes.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810103838.1A CN108079000A (en) | 2018-02-01 | 2018-02-01 | A kind of pharmaceutical composition for treating diabetes and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810103838.1A CN108079000A (en) | 2018-02-01 | 2018-02-01 | A kind of pharmaceutical composition for treating diabetes and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108524536A (en) * | 2018-06-27 | 2018-09-14 | 薛士军 | A kind of pharmaceutical composition and preparation method thereof for treating diabetes |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1244801A (en) * | 1997-02-19 | 2000-02-16 | 沃尼尔·朗伯公司 | Sulfonylurea-glitazone synergistic combinations for diabetes |
| CN101578284A (en) * | 2006-09-19 | 2009-11-11 | 协和发酵生化株式会社 | Agent for improving insulin resistance |
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2018
- 2018-02-01 CN CN201810103838.1A patent/CN108079000A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1244801A (en) * | 1997-02-19 | 2000-02-16 | 沃尼尔·朗伯公司 | Sulfonylurea-glitazone synergistic combinations for diabetes |
| CN101578284A (en) * | 2006-09-19 | 2009-11-11 | 协和发酵生化株式会社 | Agent for improving insulin resistance |
Non-Patent Citations (1)
| Title |
|---|
| MAYUMI T等: "Pyrroloquinoline quinone, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves impaired glucose tolerance in diabetic KK-Ay mice", 《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108524536A (en) * | 2018-06-27 | 2018-09-14 | 薛士军 | A kind of pharmaceutical composition and preparation method thereof for treating diabetes |
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