CN105213398B - A kind of pharmaceutical composition for treating diabetes - Google Patents
A kind of pharmaceutical composition for treating diabetes Download PDFInfo
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- CN105213398B CN105213398B CN201510590243.XA CN201510590243A CN105213398B CN 105213398 B CN105213398 B CN 105213398B CN 201510590243 A CN201510590243 A CN 201510590243A CN 105213398 B CN105213398 B CN 105213398B
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- sitagliptin
- jamaicin
- diabetes
- officinal salt
- pharmaceutical composition
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Abstract
The invention discloses a kind of pharmaceutical composition for treating diabetes, comprising as the sitagliptin of active ingredient or its officinal salt and jamaicin or its officinal salt.Blood sugar level can be effectively reduced using said composition and improves body glucose tolerance level, its significant effect is better than single use sitagliptin or jamaicin, on the premise of equal curative effect is ensured, drug combination can reduce the dosage of each medicine, strengthen the tolerance of diabetic's long-term prescription, reduce the occurrence probability of drug side-effect, in addition, drug combination can not only prevent diabetic duration from further deteriorating, and can improve the diabetes pathogenesis occurred.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of pharmaceutical composition for treating diabetes, more particularly to one
Kind contains sitagliptin or its officinal salt and the pharmaceutical composition of jamaicin or its officinal salt.
Background technology
Diabetes are a kind of common endocrine metabolism diseases characterized by hyperglycaemia.The main pathologic, physiologic of diabetes
Change turns to that defect of insulin secretion or its biological agent are impaired to prevent glucose to cause body sugar, egg from normally being utilized by body
The metabolic disorders such as white matter, fat, water and electrolyte.In recent years, with the raising of living standards of the people, living-pattern preservation and
Aging population, the incidence of disease of diabetes constantly raise.According to IDF (International Diabetes
Federatio, IDF) count, global diabetic in 2014 has 3.87 hundred million, global incidence 8.3%, estimated
2035, global diabetes number can reach 5.92 hundred million.Diabetology branch of Chinese Medical Association is in 2007 to 2008 years in China
The Diabetes Epidemiological Investigation that some areas are carried out is shown：More than the 20 years old crowd's diabetes prevalence in China is 9.7%, glycosuria
The ratio of sick early stage is 15.5%.Diabetes are a kind of chronic diseases, and along with the extension of the course of disease, various metabolic disorders can cause
Various tissues, particularly eye, kidney, heart, blood vessel, the chronic lesion of nerve and dysfunction, the cardiovascular and cerebrovascular diseases thus triggered
Change, renal failure, blindness, lower limb gangrene etc. disable the main reason for lethal as diabetes.There are 4,900,000 people in the whole world within 2014
Die from diabetes.Diabetes not only bring the human body and spiritual infringement to diseased individuals and cause the shortening in life-span, return
Personal, country brings heavy financial burden.Prevention prediabetes is converted to diabetes and carried out to having diagnosed patient
Good treatment is most important strategy in Guidelines for Management of Diabetes Mellitus.
Diabetes B accounts for all diabetes more than 90%, and its pathogenesis has two basic links：Insulin resistance and pancreas
Island β cell insulin secretion relative deficiencies.Insulin resistance refers to that the target organ of the insulin actions such as liver, muscle, fat aligns
The insulin of normal concentration produces hyporeactive pathological and physiological condition.In this state, beta Cell of islet needs to secrete more
Insulin (hyperinsulinemia sign) resists hyperglycaemia.It is tight all the more to resist that beta Cell of islet can not produce enough insulin
The insulin resistance of weight, ultimately results in beta Cell of islet exhaustion.
Diabetes B is a kind of disease of chronic progressive, and Most patients need lifelong medication.Traditional anti-glycosuria
Medicine single therapy strategy can not keep the long-term up to standard of glycemic control.According to statistics, single therapy is after 3 years, about 50%
Diabetic needs therapeutic alliance, and the ratio rises to 75% after 9 years.With the extension for the treatment of time, Most patients need to lead to
Crossing a variety of treated with combined medication can just make glycemic control up to standard.Compared with single therapy, therapeutic alliance hypoglycemic amplitude is larger, helps
In the glycemic control compliance rate for improving patient, the occurrence risk of all kinds of complication of diabetes is further reduced, improves the length of patient
Phase prognosis.Therapeutic alliance is diabetes B treatment trend.
Jamaicin is also known as berberine, a kind of common morphinane alkaloid, is present in many plants of the section 10 of Berberidaceae etc. 4 category
In thing.Clinical conventional jamaicin form is Berberine hydrochloride at present.Lot of documents shows, jamaicin have extraordinary lipid-loweringing and
Blood sugar reducing function.The mechanism of jamaicin hypoglycemic mainly increases insulin sensitivity, has certain promoting insulin secretion concurrently.
Sitagliptin is first DPP-4 inhibitor ratified for treating diabetes B.Sitagliptin can prevent
DPP-4 hydrolyzes intestines insulinotropic hormone：Glucagon-like peptide-1 (GLP-1) and glucose dependency insulin secretion accelerating polypeptide
(GIP), so as to increasing the GLP-1 of activity form and GIP plasma concentration.GLP-1 and GIP can be increased by intracellular signaling pathway
Add insulin synthesis and the release from beta Cell of islet, GLP-1 can also reduce alpha Cell of islet secretion hyperglycemic factor, make liver grape
Sugar generation is reduced, so sitagliptin is increased insulin releasing in a manner of dependence on the glucose and reduces Glucagon Levels, from
And reduce blood glucose level in patients.
So sitagliptin and jamaicin or its officinal salt are complementary in the mechanism of control diabetes, they
Drug combination may better control over diabetes, the dosage for reducing single medicine, the drug resistance for reducing diabetic, reduce
Possible adverse reaction.
At present, do not find that sitagliptin and jamaicin or its officinal salt are made by the retrieval of domestic and international public publication
Diabetes and the relevant report of its complication are treated for compound medicine.
The content of the invention
The invention provides a kind of pharmaceutical composition for treating diabetes, and blood can be effectively controlled using the pharmaceutical composition
Sugar, its significant effect are better than the effect of any one-component.
A kind of pharmaceutical composition for treating diabetes, comprising being used as the sitagliptin of active ingredient or its officinal salt and small
Bark of a cork tree alkali or its officinal salt.
Applicant has found sitagliptin or its officinal salt and jamaicin or its officinal salt drug combination energy under study for action
The effect of synergistic treatment diabetes is produced, and using only sitagliptin or its officinal salt or jamaicin or its officinal salt ratio
Compared with the therapeutic effect of composition is significantly improved.
Preferably, the sitagliptin officinal salt is one kind in sitagliptin phosphate, sulfuric acid sitagliptin.
Preferably, the jamaicin officinal salt is one in Berberine hydrochloride, berberine sulfate, nitric acid jamaicin
Kind.
Sitagliptin or the sitagliptin officinal salt (in terms of sitagliptin) can medicine with the jamaicin or jamaicin
With the concentration ratio of salt (being counted using Berberine hydrochloride) as 1:15~1:6.
The effective dose of the sitagliptin or its officinal salt (being counted using sitagliptin) is 20mg/kg~50mg/kg.
The effective dose of the jamaicin or its officinal salt (being counted using Berberine hydrochloride) is 300mg/kg.
Preferably, the pharmaceutical composition includes pharmaceutically acceptable auxiliaries.Excipient substance can assign pharmaceutical composition certain agent
Type, the release and absorption of effective ingredient is effectively ensured.
Preferably, formulation of the described pharmaceutical composition for oral administration.Oral administration is easy, not coup injury skin
Skin or mucous membrane, reduce infection risk.Because diabetic needs long-term prescription, therefore it is a kind of side of economic security to be administered orally
Formula.
More preferably, the formulation of the oral administration is solution, tablet, capsule or granule.
Beneficial effects of the present invention：Sitagliptin or the production of its officinal salt and the drug combination of jamaicin or its officinal salt
The effect of raw synergistic treatment diabetes, therapeutic effect significantly improve, and on the premise of equal curative effect is ensured, drug combination can reduce
The dosage of each medicine, strengthen the tolerance of diabetic's long-term prescription, reduce the occurrence probability of drug side-effect, separately
Outside, drug combination can not only prevent diabetic duration from further deteriorating, and can improve the diabetes pathogenesis having occurred and that.
Brief description of the drawings
Fig. 1 is each experimental group KKAy mouse fasting blood-glucose comparative result figure of embodiment 1；
Fig. 2 is each experimental group KKAy Mouse orals sugar tolerance comparative result figure of embodiment 1, and wherein A figures are OGTT detection knots
Fruit is schemed, and B figures are area result of calculation figure under plasma glucose time course；
Fig. 3 is each experimental group KKAy mouse blood sugars situation of change comparison diagram of embodiment 1；
Fig. 4 is influence of the pharmaceutical composition of embodiment 2 to KKAy mouse random blood sugar (A) and fasting blood-glucose (B)；
Wherein * represents p<0.05vs model groups, * * represent p<0.01vs model groups, * * * represent p<0.001vs model groups, #
Represent p<0.05vs compositions group, ## represent p<0.01vs composition groups.
Embodiment
With reference to specific embodiments and the drawings, the invention will be further described.But following embodiments are only the present invention
Preferred embodiment, it is and not all.Based on the embodiment in embodiment, those skilled in the art are not making creative labor
Other embodiments are obtained on the premise of dynamic, belong to protection scope of the present invention.
Embodiment 1
1st, KKAy mouse (SPF levels, male, 6-8 weeks), are provided by Beijing HFK Bio-Technology Co., Ltd..Institute
There is the equal adaptability of experimental animal to be used to test after feeding 10 days.
2nd, animal packet and processing method
Hyperglycaemia KKAy mouse are randomly divided into 4 groups, respectively model group, sitagliptin group, jamaicin group and Xi Talie
Spit of fland and berberine composition group, packet and administration such as table 1 below.The medicine of all daily gavage corresponding dosages of mouse.Model group is small
Mouse gives the carboxymethylcellulose sodium solution of equal volume solvent 0.5% (0.05%CMC-Na).
The each group animal processing mode of table 1
| Medicine | Dosage (mg/kg) | |
| Model group | \ | \ |
| Sitagliptin group | Sitagliptin | 50 |
| Jamaicin group | Berberine hydrochloride | 300 |
| Composition group | Sitagliptin+Berberine hydrochloride | 50+300 |
3rd, fasting plasma glucose
The fasting blood-glucose of a mouse is determined after administration weekly, concrete operations are as follows：After administration, water is can't help in animal fasting
6h, tail vein blood test glucose level.
Experimental result is shown in Fig. 1, and before administration, the blood sugar level of KKAy model mices is very high, more than the diagnostic criteria of diabetes.
After packet, without significant difference between model group and each administration group.Administration one week, sitagliptin group, jamaicin group and composition group
Fasting blood-glucose significantly reduces (p<0.001), the blood glucose of wherein composition group is minimum.Two weeks and after three weeks, each administration group
Blood sugar reducing function is similar with the result after one week, and wherein the blood glucose of composition group is lower than sitagliptin group, jamaicin group, illustrates west
Ta Lieting is administered with berberine composition has more preferable hypoglycemic effect than single sitagliptin, jamaicin administration.
4th, oral glucose tolerance experiment (OGTT)
Administration 4 weeks, animal overnight fasting, blood sampling are used as 0min fasting blood sugars, then give 2g/kg glucose gavages
Afterwards, distinguish tail vein bloods in 30,60, tri- time points of 120min, detect blood sugar level, draw glucose tolerance curve, calculate blood
Area under sugared time graph.
Experimental result is shown in Fig. 2A, after giving glucose (2g/kg) 30min, 60min and 120min, sitagliptin group and group
The blood glucose value of compound group is substantially less than model group；30min and 120min, the blood glucose value of jamaicin group are substantially less than model group.Such as
Shown in Fig. 2 B, relative to model group, each administration group AUC is significantly reduced.The AUC of wherein composition group is minimum, and is substantially less than west
Ta Lieting groups and jamaicin group.Compared with single drug, sitagliptin and jamaicin drug combination therapeutic effect significantly improve.
On the premise of ensureing equal curative effect, drug combination can reduce the dosage of each medicine, enhancing diabetic's long-term prescription
Tolerance, reduce the occurrence probability of drug side-effect.
5th, to the influence of diabetes development
Fasting blood sugar is compared with before being administered weekly for mouse after being administered, as shown in figure 3, model group fasting blood sugar is preceding
Lasting rise in 2 weeks, maintained an equal level to the 3rd week, illustrates diabetic duration continuous worsening；Give jamaicin or sitagliptin medicine is done
In advance, fasting blood-glucose is worth to control, maintain essentially in it is horizontal before administration, illustrate jamaicin and sitagliptin list be administered can control or
Delay the further deterioration of diabetic duration, but fasting blood-glucose can not be decreased obviously；And sitagliptin and jamaicin joint
Medication can substantially reduce fasting blood-glucose, illustrate that drug combination can not only prevent diabetic duration from further deteriorating, and can improve
The diabetes pathogenesis occurred.
Diabetes B is a kind of disease of chronic progressive, and traditional antidiabetic medicine single therapy strategy can not
Keep the long-term up to standard of glycemic control.With the development of diabetes progression, required therapeutic dose more and more higher, it is also easy to produce serious
Drug side-effect, causing the tolerance of diabetic's long-term prescription reduces, therefore multi-medicament therapeutic alliance is patient of diabetes
Person for a long time good glycemic control necessity strategy.In this research, the fasting blood-glucose of diabetic mice used is very high, in diabetes
The course of disease more serious stage, single medicine processing can not reach preferable glycemic control, and not only hypoglycemic amplitude is larger for composition, compares
The development of process is only controlled in singly administration, composition also improves the pathogenesis occurred；In addition in identical glycemic control
Under effect, composition, which avoids single pharmaceutical quantities, further increases adverse reaction caused by possibility.So this composition have it is good
Control sugar effect, the bad diabetes patient of especially more serious to clinical disease course, single medicine glycemic control have good treatment potentiality.
Embodiment 2
1st, C57BL/6, KKAy mouse (SPF levels, male), is provided by Beijing HFK Bio-Technology Co., Ltd..
All equal adaptability of experimental animal are used to test after feeding about 10 days.
2nd, animal packet and processing method
C57BL/6 mouse are randomly divided into 2 groups as a control group, by KKAy mouse：Model group, sitagliptin and jamaicin group
Compound group (sitagliptin 20mg/kg+ Berberine hydrochloride 300mg/kg).The medicine of all daily gavage corresponding dosages of mouse, mould
Type group mouse gives the carboxymethylcellulose sodium solution of equal volume solvent 0.5% (0.05%CMC-Na).
3rd, random blood sugar and fasting plasma glucose
The random blood sugar of a mouse is determined after administration weekly, concrete operations are as follows：After administration, tail vein blood detection Portugal
Grape sugar level.The fasting blood-glucose of a mouse is determined after administration weekly, after water 6h is can't help in fasting, tail vein blood detection glucose
It is horizontal.
Experimental result is shown in Fig. 4, and before administration, the blood sugar level of KKAy model mices is very high, more than the diagnostic criteria of diabetes.
After packet, no significant difference between model group and composition group.It is administered after one week, the random blood sugar and fasting blood-glucose of composition group
Reduce, illustrate that sitagliptin can be controlled well with berberine composition (sitagliptin 20mg/kg+ Berberine hydrochloride 300mg/kg)
The blood sugar level of diabetic mice processed.
Embodiment 3
Sitagliptin is prepared with Berberine hydrochloride composition tablet
Preparation technology：Microcrystalline cellulose in prescription and low substituent methyl cellulose are crossed into 80 mesh sieves, weigh the west of recipe quantity
Ta Lieting, Berberine hydrochloride are well mixed with microcrystalline cellulose and low substituent methyl cellulose, add 2% HPMC
Solution is pelletized in right amount, is dried, whole grain, and the magnesium stearate for adding recipe quantity mixes, and tabletting, produces 1000.
Embodiment 4
The preparation of sitagliptin and Berberine hydrochloride composition capsule
Preparation technology：The auxiliary materials such as microcrystalline cellulose in prescription are crossed into 80 mesh sieves respectively, weigh sitagliptin, the salt of recipe quantity
After sour jamaicin is well mixed with each auxiliary material, 5% aqueous povidone solution softwood is added, is pelletized, is dried, whole grain,
Load capsule and produce 1000.
Claims (4)
- A kind of 1. pharmaceutical composition for treating diabetes, it is characterised in that comprising as the sitagliptin of active ingredient or its can Pharmaceutical salts and jamaicin or its officinal salt；The sitagliptin officinal salt is one kind in sitagliptin phosphate and sulfuric acid sitagliptin；The jamaicin officinal salt is one kind in Berberine hydrochloride, berberine sulfate and nitric acid jamaicin；The sitagliptin or its officinal salt are in terms of sitagliptin with the jamaicin or its officinal salt with Berberine hydrochloride The concentration ratio of meter is 1:15~1:6.
- 2. pharmaceutical composition as claimed in claim 1, it is characterised in that including pharmaceutically acceptable auxiliaries.
- 3. pharmaceutical composition as claimed in claim 1, it is characterised in that described pharmaceutical composition is the formulation being administered orally.
- 4. pharmaceutical composition as claimed in claim 3, it is characterised in that the formulation of the oral administration be solution, tablet, Capsule or granule.
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| CN201510590243.XA CN105213398B (en) | 2015-09-16 | 2015-09-16 | A kind of pharmaceutical composition for treating diabetes |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510590243.XA CN105213398B (en) | 2015-09-16 | 2015-09-16 | A kind of pharmaceutical composition for treating diabetes |
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| Publication Number | Publication Date |
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| CN105213398A CN105213398A (en) | 2016-01-06 |
| CN105213398B true CN105213398B (en) | 2018-02-02 |
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2015
- 2015-09-16 CN CN201510590243.XA patent/CN105213398B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 小檗碱对糖尿病及其并发症作用的研究进展;陆静金等;《安徽医药》;20121130;第16卷(第11期);1566-1569 * |
| 治疗2 型糖尿病的新型药物———西他列汀;许菁等;《中国药物与临床》;20071130;第7卷(第11期);861-863 * |
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