CN105168203A - Application of schisandrin B in preparation of diabetes treatment drug - Google Patents
Application of schisandrin B in preparation of diabetes treatment drug Download PDFInfo
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- CN105168203A CN105168203A CN201510640266.7A CN201510640266A CN105168203A CN 105168203 A CN105168203 A CN 105168203A CN 201510640266 A CN201510640266 A CN 201510640266A CN 105168203 A CN105168203 A CN 105168203A
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Abstract
The invention discloses an application of schisandrin B in preparation of a diabetes treatment drug and provides pharmaceutical composition taking the schisandrin B as the effective component. The pharmaceutical composition can effectively reduce the blood glucose level of a diabetic patient, and the effective action concentration is far lower than metformin which is a first-line drug in the market.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of medicine of prevention and therapy diabetes, the particularly application of a kind of schisandrin B in preparation treatment diabetes medicament.
Background technology
According to IDF (InternationalDiabetesFederatio, IDF) statistics, the diabetics in the whole world in 2014 has 3.87 hundred million, and global incidence is 8.3%, estimates 2035, and global diabetes number can reach 5.92 hundred million.The Diabetes Epidemiological Investigation display that diabetology branch of Chinese Medical Association carried out in 2007 to 2008 years in China some areas: China's more than 20 years old crowd's diabetes prevalence is 9.7%, and the ratio of prediabetes is 15.5%.Diabetes are a kind of chronic diseases, along with the prolongation of the course of disease, various metabolism disorder can cause various tissue, particularly eye, kidney, heart, blood vessel, neural chronic lesion and dysfunction, the cardio cerebrovascular affection caused thus, renal failure, blind, lower limb are gangrenous etc. becomes diabetes and to disable lethal main cause.Within 2014, the whole world has 4,900,000 people to die from diabetes.Diabetes not only bring the human body and spiritual infringement to diseased individuals and cause the shortening in life-span, return individual, country brings heavy financial burden.Prevent diabetes and to transform and to most important strategy in Guidelines for Management of Diabetes Mellitus when diagnosing patient to carry out good treatment to diabetes early stage.
Type 2 diabetes mellitus accounts for all diabetes more than 90%, and its pathogenesis has two basic links: insulin resistant and beta Cell of islet insulin secretion relative deficiency.Insulin resistant refers to that the insulin of target organ to normal concentration of the insulin actions such as liver, muscle, fat produces hyporeactive pathological and physiological condition.In this state, beta Cell of islet needs to secrete more insulin (hyperinsulinemia is levied) and resists hyperglycemia.Beta Cell of islet can not produce enough islets of langerhans and usually resist insulin resistant serious all the more, finally causes beta Cell of islet exhaustion.
Type 2 diabetes mellitus is a kind of disease of chronic progressive external, and Most patients needs lifelong medication.
Fructus Schisandrae Chinensis is the dry mature fruit of magnoliaceae schisandra Schisandrachinensis (Turcz.) Baill. or schisandra chinensis SchisandrasphenantheraRehd.etWils..Effect of Fructus Schisandrae Chinensis is astringed the lung, and nourishing kidney is promoted the production of body fluid, and receives antiperspirant, arresting seminal emission.The traditional Chinese medical science claims diabetes to be diabetes, and basic pathogenesis is cloudy body fluid deficiency consumption, scorching inclined Sheng.All contain Fructus Schisandrae Chinensis in a lot for the treatment of Chinese medicine for treating diabetes prescription, some researchs show that the extract of Fructus Schisandrae Chinensis has the effect reducing diabetes glucose, but the monomer component antidiabetic effect in Fructus Schisandrae Chinensis has no any report.
Summary of the invention
The invention provides the application of schisandrin B in preparation treatment diabetes medicament, and provide a kind of to take schisandrin B as the pharmaceutical composition of effective ingredient, utilize this pharmaceutical composition effectively can control blood sugar level.
The application of schisandrin B in preparation treatment diabetes medicament.
Applicant studies and finds that schisandrin B significantly can improve insulin resistant, increases the hepatocellular glucose absorption of insulin resistant, reduces the blood sugar level of diabetics, improve glucose-tolerant level, its Be very effective.Schisandrin B can be advantageously applied to treatment diabetes, and especially type 2 diabetes mellitus and the disease relevant to diabetes, reach the object improving diabetes.
Treat a pharmaceutical composition for diabetes, comprise the schisandrin B as effective ingredient.
As preferably, schisandrin B useful effect concentration is 5 ~ 20 μMs.
As preferably, in pharmaceutical composition, the degree of schisandrin B is 22 ~ 25%.
As preferably, pharmaceutical composition comprises pharmaceutically acceptable auxiliaries.Excipient substance can give medicine certain dosage form, effectively ensures the emission and absorption of effective ingredient.
As preferably, described pharmaceutical composition is the dosage form of oral administration.Oral administration is easy, not coup injury skin or mucosa, reduces infection risk.Because diabetics needs long-term prescription, therefore oral administration is a kind of mode of economic security.
More preferred, the dosage form of described oral administration is solution, tablet, capsule or granule.
The beneficial effect that the present invention possesses: take schisandrin B as the blood sugar level that the medicine of effective ingredient significantly can reduce diabetics, its useful effect concentration is well below the market frontline medication metformin.
Accompanying drawing explanation
Fig. 1 be the schisandrin B of 5 μMs on the impact of the BNLCL.2 grape cell sugar consumption amount of insulin resistant, wherein N is Normal group, and M is model group, and vertical coordinate represents the percentage ratio of glucose relative consumption;
Fig. 2 be the schisandrin B of 10 μMs on the impact of the BNLCL.2 grape cell sugar consumption amount of insulin resistant, wherein N is Normal group, and M is model group, and vertical coordinate represents the percentage ratio of glucose relative consumption;
Fig. 3 be the schisandrin B of 20 μMs on the impact of the BNLCL.2 grape cell sugar consumption amount of insulin resistant, wherein N is Normal group, and M is model group, and vertical coordinate represents the percentage ratio of glucose relative consumption;
Fig. 4 is the impact of schisandrin B on KKAy mice fasting glucose;
Fig. 5 is the impact of schisandrin B on KKAy Mouse oral carbohydrate tolerance, and wherein A is OGTT testing result figure, B is area result figure under calculating plasma glucose time course;
Wherein, significance test method is t inspection, and * represents p<0.05vs model group, * * represents p<0.01vs model group, * * * represents p<0.001vs model group.
Detailed description of the invention
Below in conjunction with specific embodiments and the drawings, the invention will be further described.
Embodiment 1
Schisandrin B is studied insulin resistant hepatocyte hypoglycemic activity
The low-sugar type DMEM of mice embryonic hepatocyte BNLCL.2 containing 10% hyclone cultivates based on 37 DEG C, 5%CO
2hatch in cell culture incubator, change fresh medium every other day.When Growth of Cells is to 80-90%, discard culture fluid, add 3mLPBS rinse once, add 1mL0.05% trypsin-EDTA solutions and digest about 2min, add triplication culture fluid and stop digestion, by centrifugal for Cell sap 900r/min 5min, abandoning supernatant, add a certain amount of culture fluid, cell is dispelled, gets 10 μ L and count, BNLCL.2 cell is inoculated in 96 orifice plates, every hole 20,000 cell, and establish acellular blank control wells.Cultivate after 24 hours, discard former culture medium, wash one time with phosphate buffer (PBS), change serum-free without phenol red low sugar DMEM culture fluid, grouping adds by reagent.
If blank group (adding normal cell culture fluid 100 μ L), model group (adding the cell culture fluid 100 μ L containing the insulin of 1 μM), schisandrin B group (adding the cell culture fluid 100 μ L containing the insulin of 1 μM and the schisandrin B of 5 μMs), and metformin positive controls (adding the cell culture fluid 100 μ L containing the insulin of 1 μM and the metformin of 1mM).Act on after 24 hours, with the glucose content of determination of glucose oxidase every hole culture fluid, namely 5 μ L culture fluid are got in another 96 orifice plate in every hole, add 200 μ L glucoseoxidase test fluid, hatch 30min for 37 DEG C, under 492nm wavelength, measure every hole absorbance.Every hole glucose content is calculated by standard curve method in glucose 0-10mM concentration range.Every hole glucose utilization=acellular blank well culture fluid glucose content-every hole culture fluid glucose content, often group establishes more than 3 or 3 holes again, and identical experiment repeats 3 times.
After glucose content measures, former culture hole discards original fluid, and every hole adds the culture fluid containing 0.5mg/mLMTT solution, in 37 DEG C, 5%CO
2condition under hatch 4h.Abandoning supernatant, every hole adds 100 μ LDMSO, 37 DEG C, and vibration 10min, measures the absorbance in every hole, for reflecting the proliferative conditions of cell, to correct the glucose absorption difference that cell number difference causes under 550nm wavelength.Finally calculate the percentage ratio of each group of glucose utilization relative to model group consumption.
The results are shown in Figure 1, schisandrin B is that 5 μMs of BNLCL.2 cells acting on insulin resistant all can increase glucose utilization after 24 hours, through t inspection, compares have significant difference with model group.In this experiment, the useful effect concentration of positive drug metformin is 1mM.The useful effect concentration of schisandrin B is 5 μMs.
Embodiment 2
Schisandrin B is studied insulin resistant hepatocyte hypoglycemic activity
The low-sugar type DMEM of mice embryonic hepatocyte BNLCL.2 containing 10% hyclone cultivates based on 37 DEG C, 5%CO
2hatch in cell culture incubator, change fresh medium every other day.When Growth of Cells is to 80-90%, discard culture fluid, add 3mLPBS rinse once, add 1mL0.05% trypsin-EDTA solutions and digest about 2min, add triplication culture fluid and stop digestion, by centrifugal for Cell sap 900r/min 5min, abandoning supernatant, add a certain amount of culture fluid, cell is dispelled, gets 10 μ L and count, BNLCL.2 cell is inoculated in 96 orifice plates, every hole 20,000 cell, and establish acellular blank control wells.Cultivate after 24 hours, discard former culture medium, wash one time with phosphate buffer (PBS), change serum-free without phenol red low sugar DMEM culture fluid, grouping adds by reagent.
If blank group (adding normal cell culture fluid 100 μ L), model group (adding the cell culture fluid 100 μ L containing the insulin of 1 μM), schisandrin B group (adding the cell culture fluid 100 μ L containing the insulin of 1 μM and the schisandrin B of 10 μMs), and metformin positive controls (adding the cell culture fluid 100 μ L containing the insulin of 1 μM and the metformin of 1mM).Act on after 24 hours, with the glucose content of determination of glucose oxidase every hole culture fluid, namely 5 μ L culture fluid are got in another 96 orifice plate in every hole, add 200 μ L glucoseoxidase test fluid, hatch 30min for 37 DEG C, under 492nm wavelength, measure every hole absorbance.Every hole glucose content is calculated by standard curve method in glucose 0-10mM concentration range.Every hole glucose utilization=acellular blank well culture fluid glucose content-every hole culture fluid glucose content, often group establishes more than 3 or 3 holes again, and identical experiment repeats 3 times.
After glucose content measures, former culture hole discards original fluid, and every hole adds the culture fluid containing 0.5mg/mLMTT solution, in 37 DEG C, 5%CO
2condition under hatch 4h.Abandoning supernatant, every hole adds 100 μ lDMSO, 37 DEG C, and vibration 10min, measures the absorbance in every hole, for reflecting the proliferative conditions of cell, to correct the glucose absorption difference that cell number difference causes under 550nm wavelength.Finally calculate the percentage ratio of each group of glucose utilization relative to model group consumption.The results are shown in Figure 2, schisandrin B is that 10 μMs of BNLCL.2 cells acting on insulin resistant all can increase glucose utilization after 24 hours, through t inspection, compares have significant difference with model group.In this experiment, the useful effect concentration of positive drug metformin is 1mM.The valid density of schisandrin B is 10 μMs.
Embodiment 3
Schisandrin B is studied insulin resistant hepatocyte hypoglycemic activity
The low-sugar type DMEM of mice embryonic hepatocyte BNLCL.2 containing 10% hyclone cultivates based on 37 DEG C, 5%CO
2hatch in cell culture incubator, change fresh medium every other day.When Growth of Cells is to 80-90%, discard culture fluid, add 3mLPBS rinse once, add 1mL0.05% trypsin-EDTA solutions and digest about 2min, add triplication culture fluid and stop digestion, by centrifugal for Cell sap 900r/min 5min, abandoning supernatant, add a certain amount of culture fluid, cell is dispelled, gets 10 μ L and count, BNLCL.2 cell is inoculated in 96 orifice plates, every hole 20,000 cell, and establish acellular blank control wells.Cultivate after 24 hours, discard former culture medium, wash one time with phosphate buffer (PBS), change serum-free without phenol red low sugar DMEM culture fluid, grouping adds by reagent.
If blank group (adding normal cell culture fluid 100 μ L), model group (adding the cell culture fluid 100 μ L containing the insulin of 1 μM), schisandrin B group (adding the cell culture fluid 100 μ L containing the insulin of 1 μM and the schisandrin B of 20 μMs), and metformin positive controls (adding the cell culture fluid 100 μ L containing the insulin of 1 μM and the metformin of 1mM).Act on after 24 hours, with the glucose content of determination of glucose oxidase every hole culture fluid, namely 5 μ L culture fluid are got in another 96 orifice plate in every hole, add 200 μ L glucoseoxidase test fluid, hatch 30min for 37 DEG C, under 492nm wavelength, measure every hole absorbance.Every hole glucose content is calculated by standard curve method in glucose 0-10mM concentration range.Every hole glucose utilization=acellular blank well culture fluid glucose content-every hole culture fluid glucose content, often group establishes more than 3 or 3 holes again, and identical experiment repeats 3 times.
After glucose assays, former culture hole discards original fluid, and every hole adds the culture fluid containing 0.5mg/mLMTT solution, in 37 DEG C, 5%CO
2condition under hatch 4h.Abandoning supernatant, every hole adds 100 μ lDMSO, 37 DEG C, and vibration 10min, measures the absorbance in every hole, for reflecting the proliferative conditions of cell, to correct the glucose absorption difference that cell number difference causes under 550nm wavelength.Finally calculate the percentage ratio of each group of glucose utilization relative to model group consumption.
The results are shown in Figure 3, schisandrin B is that 20 μMs of BNLCL.2 cells acting on insulin resistant all can increase glucose utilization after 24 hours, through t inspection, compares have significant difference with model group.In this experiment, the useful effect concentration of positive drug metformin is 1mM.The useful effect concentration of schisandrin B is 20 μMs.
Embodiment 4
1, KKAy mice (SPF level, male, 6-8 is all), contrast C57BL/6J mice, is provided by Beijing HFK Bio-Technology Co., Ltd..The equal adaptability of all laboratory animals is fed after 10 days for experiment.
Hyperglycemia KKAy mice is divided into 2 groups at random, is respectively model group, schisandrin B group, grouping and administration are as table 1.The medicine of all mice gavage every day corresponding dosage.Matched group and model group mice give equal volume solvent 0.5% carboxymethylcellulose sodium solution (0.05%CMC-Na).
The grouping of table 1 animal and administration
| Medicine | Dosage (mg/kg) | |
| Matched group | \ | \ |
| Model group | \ | \ |
| Schisandrin B group | Schisandrin B | 100 |
2, fasting plasma glucose
Measure weekly the fasting glucose of a mice after administration, concrete operations are as follows: after administration, and water 6h is can't help in animal fasting, tail vein blood test glucose level.
3, oral glucose tolerance test (OGTT)
Administration 4 weeks, animal overnight fasting, takes a blood sample as 0min fasting blood sugar, then after giving 2g/kg glucose gavage, in 30,60,120min tri-time points tail vein bloods respectively, detect blood sugar level, draw glucose tolerance curve, area under calculating plasma glucose time course.
4, result
Fasting glucose
Experimental result is shown in Fig. 4, and before administration, the blood glucose of KKAy model mice significantly raises relative to control group mice, after grouping, without significant difference between model group and each administration group.Administration one week, the remarkable reduction compared with model group of schisandrin B group fasting glucose, two weeks and after three weeks, the effect of administration group and the result after a week similar.Illustrate that schisandrin B can control the blood sugar level of diabetic mice preferably.
Oral glucose tolerance test (OGTT)
Experimental result is shown in Fig. 5, and give 30min, 60min after glucose 2g/kg, the blood glucose value of schisandrin B group is lower than model group; Give 120min after glucose 2g/kg, the blood glucose value of schisandrin B group is significantly lower than model group (Fig. 5 A).The area under curve (AUC) of the oral glucose tolerance of model group is significantly higher than matched group; Relative to model group, administration group AUC significantly reduces.
Embodiment 5
Prepared by tablet
Preparation technology: microcrystalline Cellulose in prescription and low substituent methyl cellulose are crossed 80 mesh sieves, the schisandrin B weighing recipe quantity is mixed homogeneously with microcrystalline Cellulose and low substituent methyl cellulose, add 2% hydroxypropyl methylcellulose solution to granulate in right amount, dry, granulate, add the magnesium stearate mixing of recipe quantity, tabletting, obtains 1000.
Embodiment 6
Prepared by capsule
Preparation technology: microcrystalline Cellulose in prescription and adjuvant are crossed 80 mesh sieves respectively, the schisandrin B weighing recipe quantity adds 5% aqueous povidone solution soft material after mixing homogeneously with each adjuvant, granulate, dry, granulate, add Pulvis Talci, mixing, loads capsule and namely obtains 1000.
Claims (6)
1. the application of schisandrin B in preparation treatment diabetes medicament.
2. treat a pharmaceutical composition for diabetes, it is characterized in that, comprise the schisandrin B as effective ingredient.
3. pharmaceutical composition as claimed in claim 2, it is characterized in that, in described pharmaceutical composition, the degree of schisandrin B is 22 ~ 25%.
4. pharmaceutical composition as claimed in claim 2, is characterized in that, also comprise pharmaceutically acceptable auxiliaries.
5. pharmaceutical composition as claimed in claim 4, it is characterized in that, described pharmaceutical composition is the dosage form of oral administration.
6. pharmaceutical composition as claimed in claim 5, it is characterized in that, the dosage form of described oral administration is solution, tablet, capsule or granule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510640266.7A CN105168203A (en) | 2015-09-30 | 2015-09-30 | Application of schisandrin B in preparation of diabetes treatment drug |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510640266.7A CN105168203A (en) | 2015-09-30 | 2015-09-30 | Application of schisandrin B in preparation of diabetes treatment drug |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107243004A (en) * | 2017-04-26 | 2017-10-13 | 温州医科大学 | A kind of application of deoxyschizandrin in medicine preparation |
| CN114848825A (en) * | 2022-06-20 | 2022-08-05 | 西安交通大学 | Application of GLP-1R small molecule agonist in diabetes and related complications thereof and medicine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070020345A1 (en) * | 2005-07-22 | 2007-01-25 | The Hong Kong University Of Science And Technology | Schisandrin B preparation |
| CN103520191A (en) * | 2013-11-02 | 2014-01-22 | 苏州天南星生物科技有限公司 | Schisandra chinensis dl-tetrahydropalmatine preparation |
-
2015
- 2015-09-30 CN CN201510640266.7A patent/CN105168203A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070020345A1 (en) * | 2005-07-22 | 2007-01-25 | The Hong Kong University Of Science And Technology | Schisandrin B preparation |
| CN103520191A (en) * | 2013-11-02 | 2014-01-22 | 苏州天南星生物科技有限公司 | Schisandra chinensis dl-tetrahydropalmatine preparation |
Non-Patent Citations (1)
| Title |
|---|
| 潘瑶等: "五味子乙素的药理作用研究进展", 《吉林医药学院学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107243004A (en) * | 2017-04-26 | 2017-10-13 | 温州医科大学 | A kind of application of deoxyschizandrin in medicine preparation |
| CN107243004B (en) * | 2017-04-26 | 2023-01-20 | 温州医科大学 | Application of schisandrin B in preparation of medicine |
| CN114848825A (en) * | 2022-06-20 | 2022-08-05 | 西安交通大学 | Application of GLP-1R small molecule agonist in diabetes and related complications thereof and medicine |
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Application publication date: 20151223 |