CN106377574B - A kind of pharmaceutical composition of reducing blood lipid and preparation method thereof and purposes - Google Patents
A kind of pharmaceutical composition of reducing blood lipid and preparation method thereof and purposes Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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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
- A61K31/33—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
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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
- A61K31/33—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
- A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
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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
- A61K31/33—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
Abstract
The present invention relates to pharmaceutical composition of a kind of reducing blood lipid and preparation method thereof and purposes.The present invention is by the way that by salvianolic acid and statins administering drug combinations, the two collective effect, the pharmaceutical composition under specific proportion have significant therapeutic effect to hyperlipidemia；Moreover, the pharmaceutical composition both is significantly better than the therapeutic effect being administered alone to hyperlipidemia to the therapeutic effect of hyperlipidemia, salvianolic acid and statins administering drug combinations have the function of synergy.This shows that the pharmaceutical composition has the function of reducing blood lipid, can be used as the drug of potential reducing blood lipid.
Description
Technical field
The invention belongs to drug fields, and in particular to a kind of pharmaceutical composition of reducing blood lipid and preparation method thereof and purposes.
Background technique
Modern lifestyle makes the high protein, high cholesterol, the food of high sugar of people's intake more and more, this
The disease incidence for leading to hyperlipemia is in the trend obviously risen.Hyperlipemia be cause cardiovascular and cerebrovascular disease increased risk because
Element, and induce coronary heart disease, artery sclerosis, fatty liver, diabetes, the important risk factor of obesity.
Currently, the drug of clinical treatment hyperlipidemia, based on statins, the main atropic including Pfizer is cut down
The Simvastatin (simvastatin) of statin (Lipitor) and United States Merck company, annual sales amount reach multi-million dollar, and once
First and second of global statins antilipemic drugs market sale star's list are occupied respectively.Statins pass through
Endogenous cholesterol synthesis is reduced to be used for primary hypercholesterolemia, be associated with hypercholesterolemia and hypertriglyceridemia
Deng treatment.Since treatment hyperlipidemia needs to take blood lipid-lowering medicine for a long time, however, studies have shown that, take statins for a long time
Easily cause the toxic side effects such as transaminase raising, sarcolysis, myositis, hepatorenal damage；In addition, recent studies have shown that, Statins
Drug is also possible to greatly increase the risk of type II diabetes.Therefore, the lower reducing blood lipid of novel toxic side effect is studied
Drug is of great significance.
Radix Salviae Miltiorrhizae (Radix Salviae Miltiorrhizae) is Chun Xing section plant Radix Salviae Miltiorrhizae (Salviae
Miltiorrhiza Bunge) drying root and rhizome, be one of common drug in China's traditional medicine, there is long clinic to answer
Use history.In recent decades, pharmaceuticals researcher uses modern medicine method, in conjunction with chemical molecular biology, cell biology
Etc. multiple technologies means, the chemical component of Radix Salviae Miltiorrhizae, drug activity and pharmacological action have been carried out compared with systematic research.Study table
Bright, the chemical component of Radix Salviae Miltiorrhizae can be divided mainly into water soluble ingredient and liposoluble constituent two large divisions, and water soluble ingredient is mainly pellet
Phenolic acid compound, including salviandic acid A, tanshin polyphenolic acid B etc., danshinolic acid have the medicines such as protection cardiac muscle cell, antithrombotic, anti-oxidant
Neo-Confucianism effect；Liposoluble constituent is mainly tanshinone compound, and there are tanshinone the pharmacology such as liver protection, protection cardiac muscle cell to make
With.
Wherein, salvia-soluble effective part group and tanshin polyphenolic acid B are to the adjustment effect of ovariectomized female rats blood lipid (" in Liaoning
Medical pharmaceutical university journal ", 2008,10 (7), 146-148) disclose tanshin polyphenolic acid B and two kinds of salvia-soluble effective part groups are right
Ovariectomized female rats hyperlipemia has good effect for reducing blood fat.
However, having no that tanshin polyphenolic acid B and statins are administered in combination the report for treating hyperlipidemia.
Summary of the invention
For this purpose, the present invention proposes a kind of pharmaceutical composition of reducing blood lipid, and then provide preparation method and purposes.
In order to solve the above technical problems, the present invention is achieved through the following technical solutions:
The present invention provides a kind of pharmaceutical composition, and bulk pharmaceutical chemicals composition includes: 0.5~10 parts by weight of salvianolic acid, he
0.5~20 parts by weight of spit of fland class drug.
Preferably, in aforementioned pharmaceutical compositions of the present invention, the salvianolic acid contains tanshin polyphenolic acid B 60~65%, described
Statins are selected from Lovastatin, Simvastatin, Pravastatin, Fluvastatin, Atorvastatin, Pitavastatin, Rui Shu and cut down
Statin, cerivastatin, rosuvastatin, mevastatin.
It is further preferred that in aforementioned pharmaceutical compositions of the present invention, the salvianolic acid also contain Rosmarinic acid 35~
40%.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition includes: 1~8 weight of salvianolic acid
Part, 1~15 parts by weight of statins.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition includes: 1~8 weight of salvianolic acid
Part, 1~15 parts by weight of statins, the statins are Atorvastatin or Simvastatin.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition includes: 2.5~5 weight of salvianolic acid
Measure part, 2.5~10 parts by weight of statins.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition includes: 2.5~5 weight of salvianolic acid
Measure part, 2.5~10 parts by weight of Atorvastatin.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition includes: 2.5~5 weight of salvianolic acid
Measure part, 2.5~10 parts by weight of Simvastatin.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition includes: 2.5~5 weight of salvianolic acid
Measure part, 2.5~5 parts by weight of Atorvastatin.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition includes: 2.5 weight of salvianolic acid
Part, 5~10 parts by weight of Simvastatin.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition include:
2.5 parts by weight of salvianolic acid, 2.5 parts by weight of statins；Or
2.5 parts by weight of salvianolic acid, 5 parts by weight of statins；Or
5 parts by weight of salvianolic acid, 5 parts by weight of statins；Or
2.5 parts by weight of salvianolic acid, 10 parts by weight of statins.
It is further preferred that aforementioned pharmaceutical compositions of the present invention, bulk pharmaceutical chemicals composition include:
2.5 parts by weight of salvianolic acid, 2.5 parts by weight of Atorvastatin；Or
2.5 parts by weight of salvianolic acid, 5 parts by weight of Atorvastatin；Or
5 parts by weight of salvianolic acid, 5 parts by weight of Atorvastatin；Or
2.5 parts by weight of salvianolic acid, 5 parts by weight of Simvastatin；Or
2.5 parts by weight of salvianolic acid, 10 parts by weight of Simvastatin.
The present invention also provides the preparation methods of aforementioned pharmaceutical compositions, comprising the following steps: takes selected parts by weight respectively
Salvianolic acid and statins, be uniformly mixed to get.
The present invention also provides the preparation for including aforementioned pharmaceutical compositions or the medicines being prepared including above-mentioned preparation method
The preparation of compositions, described pharmaceutical composition are added customary adjuvant and are made clinically acceptable according to common process
Agent, capsule, powder, mixture, pill, granule, solution, syrup, soft extract, emplastrum, suppository, aerosol, ointment
Agent or injection.
The pharmaceutically acceptable auxiliary material are as follows: filler, lubricant, suspending agent, adhesive, sweetener, is rectified disintegrating agent
Taste agent, preservative, matrix etc..Filler include: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose,
Sucrose etc.；Disintegrating agent include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crosslinked polyvinylpyrrolidone,
Low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose are received；Lubricant includes: magnesium stearate, lauryl sodium sulfate, talcum
Powder, silica etc.；Suspending agent includes: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methyl cellulose
Deng；Adhesive includes starch slurry, polyvinylpyrrolidone, hydroxypropyl methyl cellulose etc.；Sweetener includes: saccharin sodium, A Si
Pa Tan, sucrose, honey element, enoxolone etc.；Corrigent includes: sweetener and various essence；Preservative include: parabens,
Benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, the fixed, eucalyptus oil of acetic acid chloroethene etc.；Matrix include: PEG6000,
PEG4000, insect wax etc..
The pharmaceutical composition being prepared the present invention also provides aforementioned pharmaceutical compositions, above-mentioned preparation method or above-mentioned medicine
The preparation of compositions is preparing the application in blood lipid-lowering medicine.
The above technical solution of the present invention has the following advantages over the prior art:
The present invention is by the way that by salvianolic acid and statins administering drug combinations, the two is made jointly under specific proportion
With the pharmaceutical composition has significant therapeutic effect to hyperlipidemia；Moreover, therapeutic effect of the pharmaceutical composition to hyperlipidemia
It both is significantly better than the therapeutic effect being administered alone to hyperlipidemia, salvianolic acid and statins, which are administered in combination, has collaboration
The effect of synergy.This shows that the pharmaceutical composition has the function of reducing blood lipid, can be used as the drug of potential reducing blood lipid.
Specific embodiment
In following embodiment of the present invention, salvianolic acid is commercially available product, wherein changing containing tanshin polyphenolic acid B 60~65% and fan
Fragrant acid 35~40%；Atorvastatin and Simvastatin are commercially available product.
Embodiment 1
The pharmaceutical composition of the present embodiment reducing blood lipid, bulk pharmaceutical chemicals composition are as follows: salvianolic acid 2.5g, Atorvastatin
2.5g；
Preparation method, comprising the following steps: take the salvianolic acid and Atorvastatin of selected weight respectively, mixing is equal
It is even to get.
Embodiment 2
The pharmaceutical composition of the present embodiment reducing blood lipid, bulk pharmaceutical chemicals composition are as follows: salvianolic acid 2.5g, Atorvastatin
5g；
Preparation method, comprising the following steps: take the salvianolic acid and Atorvastatin of selected weight respectively, mixing is equal
It is even to get.
Embodiment 3
The pharmaceutical composition of the present embodiment reducing blood lipid, bulk pharmaceutical chemicals composition are as follows: salvianolic acid 5g, Atorvastatin 5g；
Preparation method, comprising the following steps: take the salvianolic acid and Atorvastatin of selected weight respectively, mixing is equal
It is even to get.
Embodiment 4
The pharmaceutical composition of the present embodiment reducing blood lipid, bulk pharmaceutical chemicals composition are as follows: salvianolic acid 2.5g, Simvastatin 5g；
Preparation method, comprising the following steps: take the salvianolic acid and Simvastatin of selected weight respectively, mixing is equal
It is even to get.
Embodiment 5
The pharmaceutical composition of the present embodiment reducing blood lipid, bulk pharmaceutical chemicals composition are as follows: salvianolic acid 2.5g, Simvastatin 10g；
Preparation method, comprising the following steps: take the salvianolic acid and Simvastatin of selected weight respectively, mixing is equal
It is even to get.
Comparative example 1
The pharmaceutical composition of this comparative example reducing blood lipid, bulk pharmaceutical chemicals composition are as follows: tanshinone IIA 20.0g, Atorvastatin
0.1g；
Preparation method, comprising the following steps: take the tanshinone IIA and Atorvastatin of selected weight respectively, mixing is equal
It is even to get.
Experimental example
Following each experimental examples prove technical effect of the present invention.
Experimental example 1The research of the pharmaceutical composition effect for reducing blood fat of salvianolic acid and Atorvastatin
1, experimental material
1.1 drugs and reagent
In this experimental example, salvianolic acid is commercially available product, wherein containing tanshin polyphenolic acid B 60~65% and Rosmarinic acid 35~
40%；Atorvastatin is purchased from Pfizer company；
High lipid food is purchased from Nantong Te Luofei feed technology Co., Ltd；Olive oil is limited purchased from WILMAR edible oil individual
Company；Total cholesterol (TC) kit, total triglycerides (TG) kit, low-density lipoprotein (LDL) kit, millet straw turn ammonia
Enzyme (AST) kit and lactic dehydrogenase (LDH) kit are purchased from Zhong Shengbeikong Biotechnology Co., Ltd；Various other chemistry
Reagent is import or domestic analytical reagents, and experimental water is distilled water.
1.2 experimental animal
Wistar rat, SPF grades, male, is had by Si Beifu (Beijing) Laboratory Animal Science technology by 180~200 grams of weight
Limit company provides, certification of fitness SCXK (capital) 2011-0004.Animal feeding is in the cleaning grade of light and shade alternating (12h:12h)
In animal house, 20~22 DEG C of environment temperature, relative humidity 50%, ad lib drinking-water.
2, experimental method
2.1 experimental group
110 rats are carried out to be randomly divided into 11 groups according to weight, every group of 10 rats are respectively as follows: blank control group, mould
Type control group, control group 1-6 group, experimental group 1-3 group.
2.2 medication
Blank control group is fed with basal feed；Other each groups are fed with high lipid food 3 weeks, are then carried out as follows
Administration: 1 group of experimental group is given composition 5mg/kg (that is: salvianolic acid 2.5mg/kg+ Atorvastatin prepared by embodiment 1
2.5mg/kg), composition 7.5mg/kg (that is: salvianolic acid 2.5mg/kg+ atropic prepared by embodiment 2 is given for 2 groups of experimental group
Cut down statin 5mg/kg), 3 groups of experimental group are given composition 10mg/kg (that is: salvianolic acid 5mg/kg+ Ah prepared by embodiment 3
Atorvastatin 5mg/kg)；It is total that control group 1-3 group gives salvianolic acid 2.5mg/kg, salvianolic acid 5mg/kg, Radix Salviae Miltiorrhizae respectively
Phenolic acid 10mg/kg；Control group 4-6 group gives Atorvastatin 2.5mg/kg, Atorvastatin 5mg/kg, Atorvastatin respectively
10mg/kg.Each group is administered once/day, and successive administration 2 weeks.
3, experimental data detection and processing
3.1 Testing index
After last dose 1h, animal overnight fasting；After next day animal weighs in, with 10% chloraldurate (400mg/kg)
Anesthesia, abdominal aortic blood simultaneously extract liver, carry out the detection of biochemical and pathology.
The blood sample for standing 30min is centrifuged 3000rpm × 10min, it is conventional to separate serum, automatic clinical chemistry analyzer measurement
Rat total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), glutamic-oxalacetic transaminease (AST) and lactic dehydrogenase
(LDH)。
3.2 statistical analysis
Data processing is carried out using 20.0 software of SPSS, group difference is using single factor test variance (One-Way ANOVA) point
Analysis.
4, experimental result
The influence of TG level in 4.1 pairs of serum
After being administered 2 weeks, the experimental result of TG level is as shown in table 1 in the serum of each group rat.
The experimental result of TG level in 1 each group rat blood serum of table
* p < 0.05 compared with model control group is indicated；# indicates p < 0.05 compared with 1 group of control group；$ is indicated and control group 2
Group is compared；@is indicated compared with 5 groups of control group；P < 0.05.n=9-10
As shown in Table 1, (1) compared with blank control group, model control group TG it is horizontal it is significant increase (p < 0.01), this shows
High blood lipid model modeling success；(2) compared with model control group, 3 groups of control group and 6 groups of control group can significantly reduce TG in serum
Horizontal (p < 0.05)；(3) nothing is aobvious compared with model control group for 1,2 group of control group and 4,5 groups of the control group reductions to TG level
It writes sex differernce (p > 0.05)；(4) 1 group of control group is significantly better than to the reduction of TG level 2 groups of experimental group, also superior to 5 groups of control group,
And all have significant difference (p < 0.05)；(5) 2 groups of control group are significantly better than to the reduction of TG level 3 groups of experimental group, also superior to
5 groups of control group, and all have significant difference (p < 0.05).
The influence of TC level in 4.2 pairs of serum
After being administered 2 weeks, the experimental result of TC level is as shown in table 2 in the serum of each group rat.
The experimental result of TC level in 2 each group rat blood serum of table
* p < 0.05 compared with model control group is indicated；# indicates p < 0.05 compared with 1 group of control group；$ is indicated and control group 2
Group is compared；@is indicated compared with 5 groups of control group；P < 0.05.n=9-10
As shown in Table 2, (1) compared with blank control group, model control group TC it is horizontal it is significant increase (p < 0.01), this shows
High blood lipid model modeling success；(2) compared with model control group, 3 groups of control group and 5,6 groups of control group can be significantly reduced in serum
TC level (p < 0.05)；(3) nothing is aobvious compared with model control group for 1,2 group of control group and 4 groups of the control group reductions to TC level
It writes sex differernce (p > 0.05)；(4) 1 group of control group is significantly better than to the reduction of TC level 2 groups of experimental group, also superior to 5 groups of control group,
And all have significant difference (p < 0.05)；(5) 2 groups of control group are significantly better than to the reduction of TC level 3 groups of experimental group, also superior to
5 groups of control group, and all have significant difference (p < 0.05).
The influence of low-density lipoprotein (LDL) level in 4.3 pairs of serum
After being administered 2 weeks, the experimental result of LDL level is as shown in table 3 in the serum of each group rat.
The experimental result of LDL level in 3 each group rat blood serum of table
* p < 0.05 compared with model control group is indicated；# indicates p < 0.05 compared with 1 group of control group；$ is indicated and control group 2
Group is compared；@is indicated compared with 5 groups of control group；P < 0.05.n=9-10
As shown in Table 3, (1) compared with blank control group, model control group LDL it is horizontal it is significant increase (p < 0.01), this table
Bright high blood lipid model modeling success；(2) compared with model control group, 3 groups of control group and 6 groups of control group can be significantly reduced in serum
LDL level (p < 0.05)；(3) 1,2 group of control group and 4,5 groups of the control group reductions to LDL level are equal compared with model control group
There was no significant difference (p > 0.05)；(4) 1 group of control group is significantly better than to the reduction of LDL level 2 groups of experimental group, also superior to control
5 groups of group, and all have significant difference (p < 0.05)；(5) control group 2 is significantly better than to the reduction of LDL level 3 groups of experimental group
Group also superior to 5 groups of control group, and all has significant difference (p < 0.05).
The influence of glutamic-oxalacetic transaminease (AST) and lactic dehydrogenase (LDH) in 4.4 pairs of serum
After being administered 2 weeks, the experimental result of AST and LDH level is as shown in table 4 in the serum of each group rat.
The experimental result of AST and LDH level in the serum of 4 each group rat of table
* p < 0.05 compared with model control group is indicated；# indicates p < 0.05 compared with 1 group of control group；$ is indicated and control group 2
Group is compared；@is indicated compared with 5 groups of control group；P < 0.05.n=9-10
As shown in Table 4, (1) compared with blank control group, model control group LDH it is horizontal it is significant increase (p < 0.05), AST water
Head up display, which writes, increases (p < 0.05), this shows high blood lipid model modeling success；(2) compared with model control group, 3 groups of control group and right
LDH level (p < 0.05) in serum can be significantly reduced according to 6 groups of group, is significantly reduced AST level (p < 0.05) in serum；(3) right
According to 1,2 group of group and 4,5 groups of the control group reductions to LDH level there are no significant compared with model control group difference (p > 0.05),
To the reduction of AST level there are no significant compared with model control group difference (p > 0.05)；(4) 2 groups of experimental group is to LDH horizontal
Reduction is significantly better than 1 group of control group, also superior to 5 groups of control group, and all has significant difference；2 groups of experimental group to AST level
Reduction is significantly better than 1 group of control group, also superior to 5 groups of control group, and all has significant difference；(5) 3 groups of experimental group to LDH water
Flat reduction is significantly better than 2 groups of control group, also superior to 5 groups of control group, and all has significant difference (p < 0.05)；Experimental group 3
Group is significantly better than 2 groups of control group to the reduction of AST level, also superior to 5 groups of control group, and all have significant difference (p <
0.05)。
5, experiment conclusion
Pharmaceutical composition prepared by the embodiment of the present invention 2, embodiment 3 to TG, TC in the serum of hyperlipemia rat, LDL,
AST and LDH tool is significantly reduced effect；Moreover, the pharmaceutical composition is to TG, TC, LDL, AST in the serum of hyperlipemia rat
Reduction effect with LDH is significantly better than the drop that the two is administered alone TG, TC, LDL, AST and LDH in the serum to hyperlipemia rat
Low effect.Therefore, serum of the pharmaceutical composition of salvianolic acid and Atorvastatin prepared by the present invention to hyperlipemia rat
The reduction effect of middle TG, TC, LDL, AST and LDH have the function of synergy.
Experimental example 2The research of the effect for reducing blood fat of the pharmaceutical composition of salvianolic acid and Simvastatin
1, experimental material
1.1 drugs and reagent
In this experimental example, salvianolic acid is commercially available product, wherein containing tanshin polyphenolic acid B 60~65% and Rosmarinic acid 35~
40%；Simvastatin is purchased from Hangzhou MSD Corp.；
High lipid food is purchased from Nantong Te Luofei feed technology Co., Ltd；Olive oil is limited purchased from WILMAR edible oil individual
Company；Total cholesterol (TC) kit, total triglycerides (TG) kit are purchased from Zhong Shengbeikong Biotechnology Co., Ltd；It is other
Various chemical reagent are import or domestic analytical reagents, and experimental water is distilled water.
1.2 experimental animal
Wistar rat, SPF grades, male, is had by Si Beifu (Beijing) Laboratory Animal Science technology by 180~200 grams of weight
Limit company provides, certification of fitness SCXK (capital) 2011-0004.Animal feeding is in the cleaning grade of light and shade alternating (12h:12h)
In animal house, 20~22 DEG C of environment temperature, relative humidity 50%, ad lib drinking-water.
2, experimental method
2.1 experimental group
100 rats are carried out to be randomly divided into 10 groups according to weight, every group of 10 rats are respectively as follows: blank control group, mould
Type control group, control group 1-6 group, experimental group 1-2 group.
2.2 medication
In addition to blank control group, other each groups are administered 7 days as follows before modeling: 1 group of experimental group to
Give embodiment 4 preparation composition 7.5mg/kg (that is: salvianolic acid 2.5mg/kg+ Simvastatin 5mg/kg), 2 groups of experimental group
Give the composition 12.5mg/kg (that is: salvianolic acid 2.5mg/kg+ Simvastatin 10mg/kg) of the preparation of embodiment 5；Control
Group 1-3 group gives salvianolic acid 2.5mg/kg, salvianolic acid 5mg/kg, salvianolic acid 10mg/kg respectively；Control group 4-
6 groups are given Simvastatin 5.0mg/kg, Simvastatin 10.0mg/kg, Simvastatin 20.0mg/kg respectively；After administration 7 days, abdomen
Chamber injects 75% yolk lotion, and 10h is administered once again.
3, experimental data detection and processing
3.1 Testing index
After animal last dose 2h, using eyeball blood taking method, collects mouse blood and carry out biochemistry detection.30min will be stood
Blood sample be centrifuged 3000rpm × 10min, conventional to separate serum, automatic clinical chemistry analyzer measures mouse total cholesterol (TC), total
Triglycerides (TG) is horizontal.
3.2 statistical analysis
Data processing is carried out using 20.0 software of SPSS, group difference is using single factor test variance (One-Way ANOVA) point
Analysis.
4, experimental result
The influence of TG, TC level in 4.1 pairs of serum
After being administered 2 weeks, the experimental result of TG, TC level is as shown in table 5 in the serum of each group rat.
The experimental result of TG, TC level in 5 each group rat blood serum of table
* indicate that model control group compares p < 0.05；# indicates p < 0.05 compared with 1 group of control group；@is indicated and 4 groups of control group
Compared to p < 0.05；$ indicates p < 0.05 compared with 5 groups of control group；N=9-10.
As shown in Table 5, (1) compared with blank control group, model control group TG it is horizontal it is significant increase (p < 0.01), TC is horizontal
Significant to increase (p < 0.05), this shows high blood lipid model modeling success；(2) compared with model control group, 3 groups of control group and control
6 groups of group can significantly reduce TG level (p < 0.05) in serum, and 3 groups of control group and 5,6 groups of control group can significantly reduce TC in serum
Horizontal (p < 0.05)；(3) 1 group of control group is significantly better than to the reduction of TG and TC level 1 group of experimental group, also superior to 4 groups of control group,
And all have significant difference (p < 0.05)；(4) 1 group of control group is significantly better than to the reduction of TG and TC level 2 groups of experimental group,
Better than 5 groups of control group, and all have significant difference (p < 0.05).
5, experiment conclusion
Pharmaceutical composition prepared by the embodiment of the present invention 4, embodiment 5 has TG and TC level in the serum of hyperlipemia rat
It is significantly reduced effect；It is shown moreover, the pharmaceutical composition acts on the reduction of TG in the serum of hyperlipemia rat and TC level
Write the reduction effect that TG and TC level in the serum to hyperlipemia rat are administered alone better than the two.Therefore, prepared by the present invention
The pharmaceutical composition of salvianolic acid and Simvastatin has the reduction effect of TG and TC level in the serum of hyperlipemia rat
Synergistic effect.
Experimental example 3Comparative experiments
1, experimental material
1.1 drugs and reagent
In this experimental example, tanshinone IIA is purchased from Chinese pharmaceutical biological product research institute；Atorvastatin is purchased from Pfizer's system
Medicine；
High lipid food is purchased from Nantong Te Luofei feed technology Co., Ltd；Olive oil is limited purchased from WILMAR edible oil individual
Company；Total cholesterol (TC) kit, total triglycerides (TG) kit are purchased from Zhong Shengbeikong Biotechnology Co., Ltd；It is other
Various chemical reagent are import or domestic analytical reagents, and experimental water is distilled water.
1.2 experimental animal
Wistar rat, SPF grades, male, is had by Si Beifu (Beijing) Laboratory Animal Science technology by 180~200 grams of weight
Limit company provides, certification of fitness SCXK (capital) 2011-0004.Animal feeding is in the cleaning grade of light and shade alternating (12h:12h)
In animal house, 20~22 DEG C of environment temperature, relative humidity 50%, ad lib drinking-water.
2, experimental method
2.1 experimental group
70 rats are carried out to be randomly divided into 7 groups according to weight, every group of 10 rats are respectively as follows: blank control group, model
Control group, control group 1-4 group, experimental group.
2.2 medication
Blank control group is fed with basal feed；Other each groups are fed with high lipid food 3 weeks, are then carried out as follows
Administration: experimental group gives composition 10mg/kg (that is: the salvianolic acid 5mg/kg+ Atorvastatin 5mg/ of the preparation of embodiment 3
kg)；1 group of control group is given composition 210mg/kg (that is: tanshinone IIA 200mg/kg, Atorvastatin prepared by comparative example 1
10mg/kg)；2,3 groups of control group are given Atorvastatin 1mg/kg, Atorvastatin 10mg/kg respectively, and 4 groups of control group are given
Tanshinone IIA 200mg/kg.Each group is administered once/day, and successive administration 2 weeks.
3, experimental data detection and processing
3.1 Testing index
After last dose 1h, animal overnight fasting；After next day animal weighs in, with 10% chloraldurate (400mg/kg)
Anesthesia, abdominal aortic blood simultaneously extract liver, carry out the detection of biochemical and pathology.
The blood sample for standing 30min is centrifuged 3000rpm × 10min, it is conventional to separate serum, automatic clinical chemistry analyzer measurement
The total triglycerides of rat (TG), total cholesterol (TC).
3.2 statistical analysis
Data processing is carried out using 20.0 software of SPSS, group difference is using single factor test variance (One-Way ANOVA) point
Analysis.
4, experimental result
The influence of TG and TC level in 4.1 pairs of serum
After being administered 2 weeks, the experimental result of TG and TC level is as shown in table 6 in the serum of each group rat.
The experimental result of TG and TC level in the serum of 6 each group rat of table
* p < 0.05 compared with model control group is indicated；# indicates p < 0.05.n=9-10. compared with experimental group
As shown in Table 6, (1) compared with blank control group, model control group TG and TC it is horizontal it is significant increase (p < 0.01), this
Show high blood lipid model modeling success；(2) compared with model control group, 1 group of control group and experimental group can significantly reduce serum
Middle TG and TC is horizontal (p < 0.05)；(3) experimental group is significant excellent to the reduction effect of TG in the serum of hyperlipemia rat and TC level
The reduction effect of TG and TC level, has significant difference (p < 0.05) in 1 group of the control group serum to hyperlipemia rat.
5, experiment conclusion
Pharmaceutical composition prepared by the embodiment of the present invention 3 has TG and TC level in the serum of hyperlipemia rat significant
Reduction effect；Moreover, the pharmaceutical composition is significantly better than pellet to the reduction effect of TG in the serum of hyperlipemia rat and TC level
The pharmaceutical composition for joining ketone IIA and Atorvastatin acts on the reduction of TG in the serum of hyperlipemia rat and TC level.
To sum up, the present invention is by the way that by salvianolic acid and statins administering drug combinations, the two is total under specific proportion
Same-action, the pharmaceutical composition have significant therapeutic effect to hyperlipidemia；Moreover, treatment of the pharmaceutical composition to hyperlipidemia
Significant effect is administered alone the therapeutic effect to hyperlipidemia better than the two, and salvianolic acid and statins administering drug combinations have
Synergistic effect.This shows that the pharmaceutical composition has the function of reducing blood lipid, can be used as the medicine of potential reducing blood lipid
Object.
Obviously, the above embodiments are merely examples for clarifying the description, and does not limit the embodiments.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of variation or
It changes.There is no necessity and possibility to exhaust all the enbodiments.And it is extended from this it is obvious variation or
It changes still within the protection scope of the invention.
Claims (20)
1. a kind of pharmaceutical composition, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
0.5~10 parts by weight of salvianolic acid, 0.5~20 parts by weight of statins.
2. pharmaceutical composition according to claim 1, which is characterized in that
The salvianolic acid contains tanshin polyphenolic acid B 60~65%, and the statins are selected from Lovastatin, Simvastatin, general
Cut down statin, Fluvastatin, Atorvastatin, Pitavastatin, Rosuvastatin, cerivastatin, rosuvastatin, mevastatin.
3. pharmaceutical composition according to claim 2, which is characterized in that
The salvianolic acid also contains Rosmarinic acid 35~40%.
4. pharmaceutical composition according to claim 1-3, which is characterized in that its bulk pharmaceutical chemicals is by following components group
At:
1~8 parts by weight of salvianolic acid, 1~15 parts by weight of statins.
5. pharmaceutical composition according to claim 4, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
2.5~5 parts by weight of salvianolic acid, 2.5~10 parts by weight of statins.
6. pharmaceutical composition according to claim 5, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
2.5 parts by weight of salvianolic acid, 2.5 parts by weight of statins.
7. pharmaceutical composition according to claim 5, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
2.5 parts by weight of salvianolic acid, 5 parts by weight of statins.
8. pharmaceutical composition according to claim 5, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
5 parts by weight of salvianolic acid, 5 parts by weight of statins.
9. pharmaceutical composition according to claim 5, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
2.5 parts by weight of salvianolic acid, 10 parts by weight of statins.
10. pharmaceutical composition according to claim 6, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
2.5 parts by weight of salvianolic acid, 2.5 parts by weight of Atorvastatin.
11. pharmaceutical composition according to claim 7, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
2.5 parts by weight of salvianolic acid, 5 parts by weight of Atorvastatin.
12. pharmaceutical composition according to claim 8, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
5 parts by weight of salvianolic acid, 5 parts by weight of Atorvastatin.
13. pharmaceutical composition according to claim 7, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
2.5 parts by weight of salvianolic acid, 5 parts by weight of Simvastatin.
14. pharmaceutical composition according to claim 9, which is characterized in that its bulk pharmaceutical chemicals is composed of the following components:
2.5 parts by weight of salvianolic acid, 10 parts by weight of Simvastatin.
15. a kind of preparation method of the described in any item pharmaceutical compositions of claim 1-14, which is characterized in that including following step
It is rapid:
Take the salvianolic acid and statins of selected parts by weight respectively, be uniformly mixed to get.
16. include the described in any item pharmaceutical compositions of claim 1-14 preparation it is characterized in that,
Described pharmaceutical composition be added customary adjuvant, according to common process, be made clinically acceptable tablet, capsule, dissipate
Agent, mixture, pill, granule, solution, syrup, soft extract, emplastrum, suppository, aerosol, ointment or injection.
17. including the preparation for the pharmaceutical composition that preparation method described in claim 15 is prepared, which is characterized in that
Described pharmaceutical composition be added customary adjuvant, according to common process, be made clinically acceptable tablet, capsule, dissipate
Agent, mixture, pill, granule, solution, syrup, soft extract, emplastrum, suppository, aerosol, ointment or injection.
18. the described in any item pharmaceutical compositions of claim 1-14 are preparing the application in blood lipid-lowering medicine.
19. the pharmaceutical composition that preparation method described in claim 15 is prepared is preparing the application in blood lipid-lowering medicine.
20. the preparation of pharmaceutical composition described in claim 16 is preparing the application in blood lipid-lowering medicine.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1466949A (en) * | 2002-07-12 | 2004-01-14 | 苏州中药研究所 | Medicine composition for reducing blood fat |
| CN101091708A (en) * | 2006-06-22 | 2007-12-26 | 沈阳东宇药业有限公司 | Composition for reducing blood fat, and preparation method |
| CN101695492A (en) * | 2008-05-29 | 2010-04-21 | 北京奥萨医药研究中心有限公司 | Pharmaceutical composition containing statin-type lipid-lowering medicaments, sulphonylurea-type hypoglycemic medicaments and nicotinic acid |
| CN101757470A (en) * | 2008-12-25 | 2010-06-30 | 中国科学院成都生物研究所 | Blood fat lowering composition |
| CN102416015A (en) * | 2011-08-23 | 2012-04-18 | 南京正宽医药科技有限公司 | Composition containing statins and application thereof |
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2016
- 2016-06-14 CN CN201610417033.5A patent/CN106377574B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1466949A (en) * | 2002-07-12 | 2004-01-14 | 苏州中药研究所 | Medicine composition for reducing blood fat |
| CN101091708A (en) * | 2006-06-22 | 2007-12-26 | 沈阳东宇药业有限公司 | Composition for reducing blood fat, and preparation method |
| CN101695492A (en) * | 2008-05-29 | 2010-04-21 | 北京奥萨医药研究中心有限公司 | Pharmaceutical composition containing statin-type lipid-lowering medicaments, sulphonylurea-type hypoglycemic medicaments and nicotinic acid |
| CN101757470A (en) * | 2008-12-25 | 2010-06-30 | 中国科学院成都生物研究所 | Blood fat lowering composition |
| CN102416015A (en) * | 2011-08-23 | 2012-04-18 | 南京正宽医药科技有限公司 | Composition containing statins and application thereof |
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