CN107569475A - A kind of injection that there is the pharmaceutical composition for improving blood circulation effect and its application and formed by its preparation - Google Patents
A kind of injection that there is the pharmaceutical composition for improving blood circulation effect and its application and formed by its preparation Download PDFInfo
- Publication number
- CN107569475A CN107569475A CN201710705747.0A CN201710705747A CN107569475A CN 107569475 A CN107569475 A CN 107569475A CN 201710705747 A CN201710705747 A CN 201710705747A CN 107569475 A CN107569475 A CN 107569475A
- Authority
- CN
- China
- Prior art keywords
- injection
- pharmaceutical composition
- glucose
- ginkgo leaf
- kaempferol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to medical composition field, and in particular to a kind of injection for having the pharmaceutical composition for improving blood circulation effect and its application and being formed by its preparation.The pharmaceutical composition includes the total flavonoids and ginkgolides extracted by ginkgo leaf, and each component cooperates, and is clinically applied to improve blood circulation;Even more important, pine camphor and sequoyitol containing specific proportioning in the pharmaceutical composition so that the pharmaceutical composition drug effect is substantially better than existing Floium Ginkgo injection;And into distinguishing one from the other, it is quality controllable, ensure curative effect and drug safety.The present invention also provides the preparation method of pharmaceutical composition, is extracted using 95~98% alcohol refluxs, and successively uses positive and negative ion exchange resin adsorption treatment, can be effectively separated said components, and technique is simple, suitable for industrialized production.
Description
Technical field
The invention belongs to medical composition field, and in particular to a kind of to have the pharmaceutical composition for improving blood circulation effect
And its injection formed using and by its preparation.
Background technology
Disease in terms of blood circulation is to influence the common disease of human health, and patient shows as high fat of blood, hyperglycaemia, brain
Thrombus, artery sclerosis, have a lapse of memory, have a sleepless night, the symptom such as anaemia, fatiguability, osteoporosis, anoxic.
In numerous methyl-derivatives of inositol, pine camphor (D-Pinitol), sequoyitol (5-O-methyl-
Myoinositol, also known as Sequoyitol) it is most common two kinds of methyl-derivatives.Ohmoto is equal to 1980 from ginkgo
Pine camphor and sequoyitol are isolated in powder particles.Pine camphor, the molecular structure of sequoyitol are respectively as shown in formula (I) (II):
In recent years, pine camphor and sequoyitol have turned into the focus of people's research, and its increasing functional activity is constantly sent out
It is existing.Such as Chinese patent literature CN103202824A disclose loose alcohols material (such as pine camphor, D- pine camphors) prepare prevention and/control
Treat the application in the medicine or health products of obesity, high fat of blood, dyslipidemia artery sclerosis, hypertension or angiocardiopathy.And for example
Chinese patent literature CN1706369A discloses the sequoyitol and sequoyitol plant extracts for diabetes mellitus prevention and treatment, but
It is not report that sequoyitol was improving sanguimotor application also, and is not also followed on the market using its improvement blood as bulk drug
The medicine of ring.
Total flavonoids and ginkgolides are active components main in ginkgo biloba p.e, and having, which improves cardiovascular and cerebrovascular, follows
Ring, the double effects for treating cardiovascular and cerebrovascular disease.Total flavonoids be variety classes flavonol glycosides monomer general name, its structure
It is for parent nucleus with Quercetin (querctin), Kaempferol (kaempferol), Isorhamnetin (isorhamnetin) etc., and combines
The monose such as glucose, rhamnose, polysaccharide are formed;Ginkgolides mainly has Ginkgolide A. B. C etc..Research finds, ginkgo leaf institute
The total flavonoids that contain, ginkgolides constituents are because with prominent pharmacological activity, usually as ginkgo biloba p.e and its system
The quality control index composition of agent;It is harmful components and ginkgo acids composition has sensitization, its content should be controlled to ensure to use
Medicine safety.
Therefore, Chinese patent literature CN100496518C discloses a kind of ginkgo biloba p.e, the note containing the extract
Agent and preparation method thereof is penetrated, the ginkgo biloba p.e mainly contains following weight percent composition:Flavonol glycosides 10-40%, silver
Apricot lactone 2.5-25%, content of beary metal are less than 9.4ppm;Wherein, ginkgolides by following weight ratio Ginkgolides a and B
Formed with C:7-27∶3-20∶4-40.Not only active constituent content is high for above-mentioned ginkgo biloba extract, and contained ginkgo phenolic material
The impurity such as matter (such as ginkgoic acid), protein, tannin, heat source substance are less than 20ppm, the pharmaceutical preparation thus prepared, especially note
Agent is penetrated, it is evident in efficacy for cardiovascular and cerebrovascular disease, Clinical practice safety, the side effects such as injection pain, heat source response will not be produced.
But as international market is more and more high to the quality requirement of ginkgo biloba p.e and its compound preparation, such as《European Pharmacopoeia》Rule
Determine ginkgo biloba p.e total flavonoids content between 22.0~27.0%, the total amount of Ginkgolide A. B. C 2.8~
Between 3.4%, ginkgo acid content is no more than 5ppm.It is apparent that existing ginkgo biloba p.e and its preparation are difficult to reach quality
It is required that, it is impossible to ensure good therapeutic effect and drug safety.Furthermore what State Food and Drug Administration promulgated《It is Chinese medicine, natural
Drug injection main technique requirements》It is required that " ingredient should be substantially clear in injection ", and in fact, ginkgo leaf product
Kind, the place of production, growing environment and the time limit are different, and its chemical composition has differences, along with lack effective extraction separation method and
Method of quality control so that active component is complicated and indefinite in existing ginkgo biloba p.e and its formulation products, causes curative effect
Imprecise, quality is unstable.Formed in addition, not also being disclosed total flavonoids class material, ginkgolides and pine camphor, sequoyitol
Composition is used to improve sanguimotor application, and also improves blood in the form of its composition for bulk drug without appearance on the market
The medicine of circulation.Therefore, with reference to the current situation of existing ginkgo industry, it is badly in need of breaking through prior art, further R and D
Active component and functional component in ginkgo biloba p.e, will be significant for improving blood circulation.
The content of the invention
Therefore, the technical problem to be solved in the present invention is the ginkgo biloba p.e and its preparation hardly possible for overcoming prior art to prepare
It cannot be guaranteed drug safety to reach quality requirement, and active component is indefinite causes uncertain therapeutic efficacy to cut this defect, enters
And provide a kind of new sanguimotor pharmaceutical composition of improvement and its application and the injection formed by its preparation.
Therefore, the technical scheme that the application takes is:
The present invention provides a kind of pharmaceutical composition for having and improving blood circulation effect, includes the component of following parts by weight:
0.1~1 part of narcissin;
Quercetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β -0.1~1 part of D-Glucose glycosides;
Quercetin -3-O- β-D-Glucose base (1-2) -0.1~1 part of alpha-L-rhamnoside;
Kaempferol-O- β-D-Glucose base (1-2) -0.1~1 part of alpha-L-rhamnoside;
Quercetin -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] 0.1~1 part of -2-L- rhamnosides;
Kaempferol-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two]-β -0.1~1 part of D-Glucose glycosides;
Isorhamnetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β -0.1~1 part of D-Glucose glycosides;
Kaempferol-O- [6-O- (α-L- rhamnopyranosyls)]-β -0.1~1 part of D-Glucose glycosides;
Kaempferol -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] 0.1~1 part of-alpha-L-rhamnoside;
0.1~8 part of pine camphor;
0.1~2 part of sequoyitol;
0.7~2 part of ginkalide A;
0.3~1 part of ginkolide B;
0.4~1 part of ginkalide C.
Optionally, one kind in the narcissin, pine camphor, sequoyitol, ginkalide A, ginkolide B, ginkalide C or
A variety of extracted by ginkgo leaf is made.
The present invention provides the preparation for including aforementioned pharmaceutical compositions, and described pharmaceutical composition adds customary adjuvant, according to normal
Rule technique, clinically acceptable tablet, capsule, powder, mixture, pill, granule, oral liquid, syrup, cream is made
Agent, electuary, vina, injection, beverage, biscuit, candy, cake food or instant food.
The present invention provides aforementioned pharmaceutical compositions or the preparation comprising aforementioned pharmaceutical compositions is preparing improvement blood circulation
Application in medicine.
The present invention provides a kind of method for preparing the injection comprising aforementioned pharmaceutical compositions, including, by the narcissin,
Quercetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β-D-Glucose glycosides, Quercetin -3-O- β-D-Glucose base (1-
2)-alpha-L-rhamnoside, Kaempferol-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside, Quercetin -3-O- [2-O- (6-
O-)-to coumaric acyl-β-D-Glucose base] -2-L- rhamnosides, Kaempferol-O- [2-O, the 6-O- (rhamnoses of α-L- two
Base]-β-D-Glucose glycosides, Isorhamnetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β-D-Glucose glycosides, Kaempferol -
3-O- [6-O- (α-L- rhamnopyranosyls)]-β-D-Glucose glycosides, Kaempferol -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-
Glucosyl group]-alpha-L-rhamnoside, pine camphor, sequoyitol, ginkalide A, ginkolide B, ginkalide C mix with water, auxiliary material
Sterile solution is made;Wherein, content of the sequoyitol in the sterile solution is 0.1~2mg/ml.
The present invention also provides the preparation method of aforementioned pharmaceutical compositions, comprises the following steps:
(1) after taking ginkgo leaf to crush, 95~98% alcohol refluxs is added and are extracted 3~5 times, each reflux extracting time is
0.5~0.7 hour, the quality for adding 95~98% ethanol every time was 9.5~11.5 times of the ginkgo leaf quality;Cross
Filter, gained filtrate decompression is concentrated into 0.15~0.25 times of the ginkgo leaf quality, refrigerated 45~51 hours;
(2) oil slick is scraped off, takes subnatant;
(3) water for injection is added into the subnatant to 0.4~0.6 times of the ginkgo leaf quality, refrigerates 45~51
Hour;Filtering, 0.15~0.25 times of the ginkgo leaf quality is concentrated into by gained filtrate decompression, is put to room temperature, add 95~
98% ethanol, alcohol content is set the solution after alcohol precipitation to be refrigerated, filtered and concentrated successively to 78~82%, repeat 2~
3 times;
(4) water for injection is added to 0.15~0.25 times of the ginkgo leaf quality to the filtrate after concentration, first use sun
Ion exchange resin carries out absorption 3~5 times, then carries out absorption 3~5 times with the attached resin of anion again;Wherein, the resin cation
Dosage is 0.8~1.2 times of the ginkgo leaf quality, the resin anion (R.A.) dosage for the ginkgo leaf quality 0.26~
0.40 times of amount;
(5) auxiliary material and water are added to the decoction of adsorption treatment, is made sterile solution, sequoyitol contains in the sterile solution
Measure as 0.1~2mg/mL.
Optionally, the resin cation granularity is 30~60 mesh;The resin anion (R.A.) granularity is 30~60 mesh.
Optionally, the pH value of the sterile solution is 4.0~7.0.
Optionally, in the sterile solution, ginkgoic acid≤20ng/ml, the μ g/ml of lead content≤0.6, the μ of cadmium content≤0.15
G/ml, the μ g/ml of arsenic content≤0.3, the μ g/ml of mercury content≤0.1, the μ g/ml of copper content≤7.5.
The present invention also provides the injection for being prepared and being formed by the above method.
Technical solution of the present invention, have the following advantages that:
1. a kind of pharmaceutical composition with improvement blood circulation effect of present invention offer, including 0.1~1 part of narcissin,
Quercetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β -0.1~1 part of D-Glucose glycosides, Quercetin -3-O- β-D- Portugals
Grape glycosyl (1-2) -0.1~1 part of alpha-L-rhamnoside, Kaempferol-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside 0.1
~1 part, Quercetin -3-O- [2-O- (6-O-)-to coumaric acyl-β-D glucosyl groups] 0.1~1 part of -2-L- rhamnosides, Mongolian oak
Pi Su -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] 0.1~1 part of -2-L- rhamnosides, Isorhamnetin -
3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β -0.1~1 part of D-Glucose glycosides, Kaempferol-O- [6-O- (α-L- sandlwoods
Glycosyl)]-β -0.1~1 part of D-Glucose glycosides, Kaempferol -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] -
0.1~1 part of alpha-L-rhamnoside, 0.1~8 part of pine camphor, 0.1~2 part of sequoyitol, 0.7~2 part of ginkalide A, ginkolide B
0.3~1 part, 0.4~1 part of ginkalide C.Contained component understands in the pharmaceutical composition, quality controllable, both can guarantee that curative effect
Prominent, and can ensures drug safety;Each component cooperates, and can clinically be applied to improve blood circulation, especially add
The pine camphor and sequoyitol of specific proportioning so that be substantially better than existing Floium Ginkgo injection the effect of the pharmaceutical composition.In addition,
China's gingko resource enriches so that the acquisition of total flavonoids is more convenient, and ginkgolides, pine camphor, sequoyitol not only may be used
To be extracted from ginkgo leaf, can also use it is commercially available, cheap, application prospect is wider.
2. the present invention provides the preparation method of aforementioned pharmaceutical compositions, ginkgo leaf successively by alcohol extracting, water is heavy, alcohol precipitation, suction
The technique such as attached obtains ginkgo biloba p.e, using the extraction of 95~98% alcohol refluxs and successively using resin cation, it is cloudy from
Subtree fat carries out absorption and is used cooperatively, and the active material in ginkgo leaf can be carried out to effectively extraction and be separated, into distinguishing one from the other,
And the ginkgo biloba p.e prepared with this meets industry quality standard, ensure curative effect, drug safety.In addition, what the present invention used
Extraction process cost is low, simple to operate, suitable for industrialized production.
3. the present invention is also provided using the injection being prepared by aforementioned pharmaceutical compositions, through animal experiment, Neng Gouming
The aobvious function with reaming capillary, fine motion vascular and venule diamater, and increase velocity of blood flow, increase CBF, have very much
Beneficial to Clinical practice.
Embodiment
For the ease of understanding the purpose of the present invention, technical scheme and main points, embodiments of the present invention will be made below into
One step is described in detail.The present invention can be implemented with many different forms, and should not be construed as being limited to reality set forth herein
Apply example.Conversely, there is provided this embodiment so that the present invention will be thoroughly and completely, and will the design of the present invention is abundant
Those skilled in the art are communicated to, the present invention will only be defined by the appended claims.
Embodiment 1
The present invention provides a kind of preparation method of the injection for the pharmaceutical composition for having and improving blood circulation effect, including
Following steps:
(1) after taking ginkgo leaf to crush, adding 95% alcohol reflux and extract 3 times, each reflux extracting time is 0.5 hour,
The quality for adding 95% ethanol every time is 10 times of the ginkgo leaf quality;Filtering, ginkgo leaf is concentrated into by gained filtrate decompression
0.2 times of quality, refrigerate 48 hours;
(2) oil slick is scraped off, takes subnatant;
(3) water for injection is added into subnatant to 0.5 times of ginkgo leaf quality, is refrigerated 48 hours;Filtering, filtrate is subtracted
Pressure is concentrated into 0.2 times of ginkgo leaf quality, puts to room temperature, adds 95% ethanol, make alcohol content to 80%, by the solution after alcohol precipitation
Refrigerated, filtered and concentrated successively, repeated 2 times;
(4) to the filtrate addition water for injection after concentration to 0.2 times of ginkgo leaf quality, first using 40 mesh resin cations
Absorption 3 times is carried out, then carries out absorption 3 times with the 50 attached resins of mesh anion again.Wherein, resin cation dosage is the ginkgo food value of leaf
1.0 times of amount, resin anion (R.A.) dosage are 0.33 times of ginkgo leaf quality;
(3) auxiliary material and water are added to the decoction of adsorption treatment, sterile solution, pH=5 is made.
Detected using high performance liquid chromatography, in above-mentioned sterile solution, its narcissin 0.71mg/ml;Quercetin -3-O-
[2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β-D-Glucose glycosides 0.10mg/ml;Quercetin -3-O- β-D-Glucose base (1-
2)-alpha-L-rhamnoside 0.59mg/ml;Kaempferol-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside 0.60mg/ml;
Quercetin -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] -2-L- rhamnosides 0.10mg/ml;Kaempferol-
3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two]-β-D-Glucose glycosides 0.10mg/ml;Isorhamnetin -3-O- [2-O, 6-O- (α -
The rhamnopyranosyls of L- bis-)]-β-D-Glucose glycosides 0.10mg/ml;Kaempferol-O- [6-O- (α-L- rhamnopyranosyls)]-β-D- grapes
Glucosides 0.47mg/ml;Kaempferol -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base]-alpha-L-rhamnoside
0.77mg/ml;Pine camphor 8.00mg/ml;Sequoyitol 1.04mg/ml;Ginkalide A 0.70mg/ml;Ginkolide B 0.30mg/
ml;Ginkalide C 0.40mg/ml.
Embodiment 2
The present invention provides a kind of preparation method of the injection for the pharmaceutical composition for having and improving blood circulation effect, including
Following steps:
(1) after taking ginkgo leaf to crush, adding 97% alcohol reflux and extract 4 times, each reflux extracting time is 0.7 hour,
The quality for adding 97% ethanol every time is 11.5 times of the ginkgo leaf quality;Filtering, ginkgo is concentrated into by gained filtrate decompression
0.25 times of leaf quality, refrigerate 51 hours;
(2) oil slick is scraped off, takes subnatant;
(3) water for injection is added into subnatant to 0.4 times of ginkgo leaf quality, is refrigerated 45 hours;Filtering, filtrate is subtracted
Pressure is concentrated into 0.25 times of ginkgo leaf quality, puts to room temperature, adds 97% ethanol, make alcohol content to 82%, will be molten after alcohol precipitation
Liquid is refrigerated, filtered and concentrated successively, is repeated 3 times;
(4) to the filtrate addition water for injection after concentration to 0.15 times of ginkgo leaf quality, first using 30 mesh cation trees
Fat carries out absorption 5 times, then carries out absorption 4 times with the 60 attached resins of mesh anion again.Wherein, resin cation dosage is ginkgo leaf
0.8 times of quality, resin anion (R.A.) dosage are 0.26 times of ginkgo leaf quality;
(3) auxiliary material and water are added to the decoction of adsorption treatment, sterile solution, pH=7 is made.
Detected using high performance liquid chromatography, in above-mentioned sterile solution, its narcissin 0.10mg/ml;Quercetin -3-O-
[2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β-D-Glucose glycosides 0.52mg/ml;Quercetin -3-O- β-D-Glucose base (1-
2)-alpha-L-rhamnoside 0.10mg/ml;Kaempferol-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside 0.10mg/ml;
Quercetin -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] -2-L- rhamnosides 0.70mg/ml;Kaempferol-
3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two]-β-D-Glucose glycosides 0.42mg/ml;Isorhamnetin -3-O- [2-O, 6-O- (α -
The rhamnopyranosyls of L- bis-)]-β-D-Glucose glycosides 0.37mg/ml;Kaempferol-O- [6-O- (α-L- rhamnopyranosyls)]-β-D- grapes
Glucosides 0.10mg/ml;Kaempferol -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base]-alpha-L-rhamnoside
1.00mg/ml;Pine camphor 4.94mg/ml;Sequoyitol 0.10mg/ml;Ginkalide A 1.76mg/ml;Ginkolide B 0.81mg/
ml;Ginkalide C 0.74mg/ml.
Embodiment 3
The present invention provides a kind of preparation method of the injection for the pharmaceutical composition for having and improving blood circulation effect, including
Following steps:
(1) after taking ginkgo leaf to crush, adding 98% alcohol reflux and extract 5 times, each reflux extracting time is 0.6 hour,
The quality for adding 98% ethanol every time is 9.5 times of the ginkgo leaf quality;Filtering, ginkgo leaf is concentrated into by gained filtrate decompression
0.15 times of quality, refrigerate 45 hours;
(2) oil slick is scraped off, takes subnatant;
(3) water for injection is added into subnatant to 0.6 times of ginkgo leaf quality, is refrigerated 51 hours;Filtering, filtrate is subtracted
Pressure is concentrated into 0.15 times of ginkgo leaf quality, puts to room temperature, adds 98% ethanol, make alcohol content to 78%, will be molten after alcohol precipitation
Liquid is refrigerated, filtered and concentrated successively, is repeated 2 times;
(4) to the filtrate addition water for injection after concentration to 0.25 times of ginkgo leaf quality, first using 60 mesh cation trees
Fat carries out absorption 4 times, then carries out absorption 5 times with the 30 attached resins of mesh anion again.Wherein, resin cation dosage is ginkgo leaf
1.2 times of quality, resin anion (R.A.) dosage are 0.40 times of ginkgo leaf quality;
(3) auxiliary material and water are added to the decoction of adsorption treatment, sterile solution, pH=4 is made.
Detected using high performance liquid chromatography, in above-mentioned sterile solution, its narcissin 1.00mg/ml;Quercetin -3-O-
[2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β-D-Glucose glycosides 0.10mg/ml;Quercetin -3-O- β-D-Glucose base (1-
2)-alpha-L-rhamnoside 1.00mg/ml;Kaempferol-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside 1.00mg/ml;
Quercetin -3-O- [2-O- (6-O-)-to coumaric acyl-β-D glucosyl groups] -2-L- rhamnosides 1.00mg/ml;Kaempferol-
3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two]-β-D-Glucose glycosides 1.00mg/ml;Isorhamnetin -3-O- [2-O, 6-O- (α -
The rhamnopyranosyls of L- bis-)]-β-D-Glucose glycosides 1.00mg/ml;Kaempferol-O- [6-O- (α-L- rhamnopyranosyls)]-β-D- grapes
Glucosides 1.00mg/ml;Kaempferol -3-O- [2-O- (6-O-)-to coumaric acyl-β-D glucosyl groups]-alpha-L-rhamnoside
0.10mg/ml;Pine camphor 0.1mg/ml;Sequoyitol 2.00mg/ml;Ginkalide A 2.00mg/ml;Ginkolide B 1.00mg/
ml;Ginkalide C 1.00mg/ml.
Test example 1
Injection prepared by the sterile solution that embodiment 1-3 is provided is subjected to total flavonoids, ginkgoic acid, heavy metal respectively
Detection, its result are as follows:
The testing result of the sterile solution of table 1
As shown in Table 1, the ginkgo biloba p.e obtained using the embodiment 1-3 techniques provided, quality controllable, quality is steady
Fixed, harmful components meet professional standard, can ensure drug safety.
Test example 2
In order to further prove the performance of injection provided by the invention, the injection that the present invention is prepared using embodiment 1-3
Following experiment has been done in agent:
The influence of 1 pair of rabbit blood circulation
1.1 material
Injection prepared by the sterile solution that Shu Xuening injection (Shineway Pharmaceutical Co., Ltd) and embodiment 1-3 are provided respectively
Agent ZHW-1, ZHW-2, ZHW-3, distinguish wiring solution-forming with physiological saline;
Weight winestone norepinephrine (Shanghai Hefeng Pharmaceutical Co., Ltd.), temporarily with physiology salt be configured to 0.01% it is molten
Liquid;
Liquaemin (Solution on Chemical Reagents in Shanghai factory), the interim heparin solution with normal saline into 500 units/ml.
1.2 Floium Ginkgo injection pine camphors, sequoyitol experimental study
1.2.1 test apparatus and material
Instrument:Agilentl260-3 high performance liquid chromatographs, METTLER XS205 electronic balances;
Chromatographic column:COSMOSIL5NH2-MS 250*4.6IDmm;
Reference substance:D- pine camphors (U.S. logical sequence biology, lot number A0622AS, purity 95%), sequoyitol (U.S. logical sequence biology, lot number
A0610A, purity 98%);
Test sample:Shu Xuening injection (martial prowess medicine company);
Reagent:Acetonitrile (chromatographically pure, Beijing Dick horse Science and Technology Ltd.), water (Wahaha Pure Water).
1.2.2 method of testing
Chromatographic condition:Acetonitrile-water (90.5: 9.5) is mobile phase;Column temperature is 30 DEG C;Flow velocity is 1.5ml/min;Evaporative light
Detector;Drift tube temperature:105℃;Gain:1;Nebulizer gas pressure:3.0b.
The preparation of reference substance solution:Divide and take pine camphor reference substance, sequoyitol reference substance each appropriate, add water that every 1ml is made and contain 1mg
Solution, shake up, filter, produce.
The preparation of need testing solution:Shu Xuening injection is taken as need testing solution.
Detection method:It is accurate respectively to draw μ l of reference substance solution 3, the μ l of need testing solution 5, inject liquid chromatograph, measure.
Content is calculated with 2 logarithmic equations of external standard.
1.2.3 test result
Shu Xuening injection does not detect pine camphor, sequoyitol.
1.3 animals and grouping experiment
From the big ear rabbit of healthy adult, male and female are unlimited, body weight (2.1 ± 0.2) kg.It is randomly divided into 7 groups:Normal group,
Microcirculation disorder group (NE), microcirculation disorder improvement group (physiological saline group, Shu Xuening injection group, ZHW-1 injections group,
ZHW-2 injections group, ZHW-3 injections group).
1.4 method
Arteries of Rabbits blood pressure, heart rate, the measure of electrocardiogram and each parameter of microcirculation:
With 20% urethanes (0.5ml/100gBW) during experiment, auricular vein injecting anesthetic is fixed, isolates a left side
Side arteria carotis communis, row arterial cannulation, interior injection heparin solution anti-freezing is managed, connects blood pressure sensor and the life of BL-2000 multichannels
Thing Functional Experiment system (Chengdu TME Technology Co., Ltd.'s development), record arterial pressure.It is subcutaneous that animal foot is inserted in acupuncture needle
Portion, synchronous recording electrocardiogram and heart rate.After belly cropping, long 3cm stringer otch, blunt separation flesh are done by the rectus aabdominis of right side
Meat, it is light to pull out 4~5cm sections ileum and intestinal loop on caecum, it is placed in constant temperature perfusion box, continuous perfusion LockeShi liquid (NaCl
9.2g/L, KCl 0.42g/L, CaCl20.23g/L, NaHCO30.67g/L, glucose 1.0g/L, 95%O2+ 5%CO2, pH
7.35).Bath temperature is maintained at (37.5 ± 0.5) DEG C, using BI-2000 Microcirculatory Images analysis system (Chengdu Tai Meng science and technology
Co., Ltd develops) observe and record, post surgery stabilization 10min is tested again.
In the case of blood pressure, heart rate and electrocardiogram Simultaneous Monitoring, first record and measure normal condition mesenterium ventrale capillary
The parameters such as blood vessel, venule, the caliber of arteriole, VPV and CBF, then the μ l of instillation 0.01%NE 50 cause part
Mesentery microcirculation obstacle, record result.After 5min respectively auricular vein injecting normal saline (NS), Shu Xuening injection,
ZHW-1 injections, ZHW-2 injections, ZHW-3 injections, wherein Floium Ginkgo group, ZHW-1 injections group, ZHW-2 injections group,
(0.1mL/100gBW) is administered in ZHW-3 injections group, administration concentration 5.0mg/mL.15,30min is to hair after observation each group administration
Thin blood vessel, arteriole, venule diamater, VPV and the change of CBF and arterial pressure, the change of heart rate, electrocardiogram,
And measure and record immediately.
1.5 result
1.5.1 to the influence of Rabbit Mesentery microcirculation
1.5.1.1 to the influence of capillary caliber, velocity of blood flow and CBF
Influence of the table 2 to capillary caliber, velocity of blood flow and CBF
As seen from Table 2, on the basis of Normal group, the local μ l of instillation 0.01%NE 50 cause Mesentery microcirculation
Obstacle, compared with Normal group, as a result be capillary caliber reduce (P < 0.01), velocity of blood flow slow down (P < 0.01),
CBF declines (P < 0.01).ZHW-1 groups, ZHW-2 groups, ZHW-3 groups, Shu Xuening injection group are compared with NE obstacle groups, capillary
Blood vessels caliber, VPV, CBF have significant differences (P < 0.01).And the NS groups of same dose, no conspicuousness
Difference (P > 0.05).It is apparent that ZHW-1 injections group, ZHW-2 injections group, ZHW-3 injection groups are superior to Floium Ginkgo note
Penetrate liquid group.
1.5.1.2 to the influence of arteriole caliber, velocity of blood flow and CBF
Influence of the table 3 to arteriole caliber, velocity of blood flow and CBF
As seen from Table 3, it is as a result similar with capillary.ZHW-1 injections group, ZHW-2 injections group, ZHW-3 injections
Compared with NE obstacle groups, arteriole caliber has significant difference (P < 0.05) in 30min for agent group, Shu Xuening injection group,
There is highly significant when ZHW-1 injections group, ZHW-2 injections group, ZHW-3 injections group, Shu Xuening injection group 15,30min
Sex differernce (P < 0.01);Arteriole velocity of blood flow ZHW-1 injections group, ZHW-2 injections group, ZHW-3 injections group, relax
Xuening injection group has significant difference (P < 0.05).Arteriole CBF has significant differences (P < 0.01).And
The NS groups of same dose, there was no significant difference (P > 0.05).It is apparent that ZHW-1 injections group, ZHW-2 injections group, ZHW-3
Injection group is superior to Shu Xuening injection group.
1.5.1.3 to the influence of venule diamater, velocity of blood flow and CBF
Influence of the table 4 to venule diamater, velocity of blood flow and CBF
As seen from Table 4, it is as a result also similar to above-mentioned two.Floium Ginkgo group and ZHW-1 injections group, ZHW-2 injections group,
For ZHW-3 injections group compared with NE obstacle groups, venule diamater has significant difference (P < 0.05), ZHW-1 notes in 15min
Penetrating agent group, ZHW-2 injections group, ZHW-3 injections, Shu Xuening injection group has significant differences (P < 0.01);It is micro- quiet
Arteries and veins velocity of blood flow ZHW-1 injections group, ZHW-2 injections group, ZHW-3 injections, Shu Xuening injection group have significant difference
(P < 0.05);Venule CBF has significant differences (P < 0.01).And the NS groups of same dose, no conspicuousness are poor
Different (P > 0.05).It is apparent that ZHW-1 injections group, ZHW-2 injections group, ZHW-3 injections are superior to Shu Xuening injection
Group.
Obviously, above-described embodiment is only intended to clearly illustrate example, and is not the restriction to embodiment.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 change or
Change.There is no necessity and possibility to exhaust all the enbodiments.And the obvious change thus extended out or
Among changing still in the protection domain of the invention.
Claims (10)
1. a kind of have the pharmaceutical composition for improving blood circulation effect, it is characterised in that includes the component of following parts by weight:
0.1~1 part of narcissin;
Quercetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β -0.1~1 part of D-Glucose glycosides;
Quercetin -3-O- β-D-Glucose base (1-2) -0.1~1 part of alpha-L-rhamnoside;
Kaempferol-O- β-D-Glucose base (1-2) -0.1~1 part of alpha-L-rhamnoside;
Quercetin -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] 0.1~1 part of -2-L- rhamnosides;
Kaempferol-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two]-β -0.1~1 part of D-Glucose glycosides;
Isorhamnetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β -0.1~1 part of D-Glucose glycosides;
Kaempferol-O- [6-O- (α-L- rhamnopyranosyls)]-β -0.1~1 part of D-Glucose glycosides;
Kaempferol -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] 0.1~1 part of-alpha-L-rhamnoside;
0.1~8 part of pine camphor;
0.1~2 part of sequoyitol;
0.7~2 part of ginkalide A;
0.3~1 part of ginkolide B;
0.4~1 part of ginkalide C.
2. pharmaceutical composition according to claim 1, it is characterised in that the narcissin, pine camphor, sequoyitol, in ginkgo
One or more extracted by ginkgo leaf in ester A, ginkolide B, ginkalide C is made.
3. a kind of include as the preparation of the pharmaceutical composition described in claim 1 or 2, it is characterised in that described pharmaceutical composition
Customary adjuvant is added, according to common process, clinically acceptable tablet, capsule, powder, mixture, pill, particle is made
Agent, oral liquid, syrup, paste, electuary, vina, injection, beverage, biscuit, candy, cake food or instant food.
4. the preparation of the pharmaceutical composition described in pharmaceutical composition or claim 3 described in claim 1 or 2 is preparing improvement
Application in blood circulation medicine.
A kind of 5. method for preparing the injection comprising the pharmaceutical composition described in claim 1 or 2, it is characterised in that including,
By the narcissin, Quercetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β-D-Glucose glycosides, Quercetin -3-O- β -
D-Glucose base (1-2)-alpha-L-rhamnoside, Kaempferol-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside, quercitrin
Element -3-O- [2-O- (6-O-)-to coumaric acyl-β-D-Glucose base] -2-L- rhamnosides, Kaempferol-O- [2-O, 6-O-
(rhamnopyranosyls of α-L- two]-β-D-Glucose glycosides, Isorhamnetin -3-O- [2-O, 6-O- (rhamnopyranosyls of α-L- two)]-β-D- Portugals
Polyglycoside, Kaempferol-O- [6-O- (α-L- rhamnopyranosyls)]-β-D-Glucose glycosides, Kaempferol -3-O- [2-O- (6-O-)-right
Coumaric acyl-β-D-Glucose base]-alpha-L-rhamnoside, pine camphor, sequoyitol, ginkalide A, ginkolide B, ginkalide C
Sterile solution is mixed and made into water, auxiliary material;Wherein, content of the sequoyitol in the sterile solution is 0.1~2mg/ml.
6. a kind of preparation method for preparing the injection comprising the pharmaceutical composition described in claim 1 or 2, including following step
Suddenly:
(1) take ginkgo leaf crush after, add 95~98% alcohol refluxs extract 3~5 times, each reflux extracting time be 0.5~
0.7 hour, the quality for adding 95~98% ethanol every time was 9.5~11.5 times of the ginkgo leaf quality;Filtering, by institute
0.15~0.25 times that filtrate decompression is concentrated into the ginkgo leaf quality is obtained, is refrigerated 45~51 hours;
(2) oil slick is scraped off, takes subnatant;
(3) water for injection is added into the subnatant to 0.4~0.6 times of the ginkgo leaf quality, is refrigerated 45~51 hours;
Filtering, 0.15~0.25 times of the ginkgo leaf quality is concentrated into by gained filtrate decompression, is put to room temperature, is added 95~98% second
Alcohol, make alcohol content that the solution after alcohol precipitation be refrigerated, filtered and concentrated successively, repeated 2~3 times to 78~82%;
(4) to the filtrate addition water for injection after concentration to 0.15~0.25 times of the ginkgo leaf quality, first using cation
Resin carries out absorption 3~5 times, then carries out absorption 3~5 times with the attached resin of anion again;Wherein, the resin cation dosage
For 0.8~1.2 times of the ginkgo leaf quality, the resin anion (R.A.) dosage is 0.26~0.40 times of the ginkgo leaf quality
Amount;
(5) auxiliary material and water are added to the decoction of adsorption treatment, is made sterile solution, the content of sequoyitol is in the sterile solution
0.1~2mg/mL.
7. the preparation method of injection according to claim 6, it is characterised in that the resin cation granularity be 30~
60 mesh;The resin anion (R.A.) granularity is 30~60 mesh.
8. the preparation method of the injection according to claim 6 or 7, it is characterised in that the pH value of the sterile solution is
4.0~7.0.
9. according to the preparation method of any described injections of claim 6-8, it is characterised in that in the sterile solution, silver
Apricot acid≤20ng/ml, the μ g/ml of lead content≤0.6, the μ g/ml of cadmium content≤0.15, the μ g/ml of arsenic content≤0.3, mercury content≤0.1
μ g/ml, the μ g/ml of copper content≤7.5.
10. a kind of method as described in claim 6-10 prepares the injection formed.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710705747.0A CN107569475A (en) | 2017-08-16 | 2017-08-16 | A kind of injection that there is the pharmaceutical composition for improving blood circulation effect and its application and formed by its preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710705747.0A CN107569475A (en) | 2017-08-16 | 2017-08-16 | A kind of injection that there is the pharmaceutical composition for improving blood circulation effect and its application and formed by its preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
CN107569475A true CN107569475A (en) | 2018-01-12 |
Family
ID=61034280
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710705747.0A Pending CN107569475A (en) | 2017-08-16 | 2017-08-16 | A kind of injection that there is the pharmaceutical composition for improving blood circulation effect and its application and formed by its preparation |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107569475A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107703237A (en) * | 2017-10-18 | 2018-02-16 | 朗致集团万荣药业有限公司 | Method that is a kind of while determining the content of pine camphor and sequoyitol in ginkgo biloba p.e |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1899323A (en) * | 2005-07-18 | 2007-01-24 | 厦门国宇知识产权研究有限公司 | Ginkgo leaf extract, injection containing said extract and its preparing method |
-
2017
- 2017-08-16 CN CN201710705747.0A patent/CN107569475A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1899323A (en) * | 2005-07-18 | 2007-01-24 | 厦门国宇知识产权研究有限公司 | Ginkgo leaf extract, injection containing said extract and its preparing method |
Non-Patent Citations (3)
Title |
---|
刘秀萍: "银杏叶提取物的研究进展与应用前景", 《药学研究》 * |
张泽生等: "D-松醇对高脂血症仓鼠血脂的影响", 《中国食品添加剂》 * |
戴丽: "红杉醇对糖尿病大鼠血管内皮的保护作用及机制研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107703237A (en) * | 2017-10-18 | 2018-02-16 | 朗致集团万荣药业有限公司 | Method that is a kind of while determining the content of pine camphor and sequoyitol in ginkgo biloba p.e |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101850066B (en) | Chinese medicinal composition granules and preparation method thereof | |
CN105582000B (en) | Application of the terpene substances in preparing treatment senile dementia or Alzheimer disease drugs in Bark of Eucommia Ulmoides or folium cortex eucommiae | |
CN101416990A (en) | Jasmine flower extract and preparation method and use thereof | |
CN103355655A (en) | Composition with alimentary anemia improving function and preparation method of composition | |
AU2007344604A1 (en) | A forsythiaside injection and preparation thereof | |
KR20180051822A (en) | Composition for skin regeneration containing absolute of hemistepta lyrata bunge flower | |
CN104147032B (en) | A kind of pharmaceutical composition for preventing and treating cerebral infarction relevant disease and its production and use | |
CN107569475A (en) | A kind of injection that there is the pharmaceutical composition for improving blood circulation effect and its application and formed by its preparation | |
CN101940605B (en) | Chinese loropetalum leaf total flavonol extract and medical application thereof | |
CN109925310A (en) | Blood-pressure drug containing therapeutically effective amount ginkgolides | |
CN100418522C (en) | High-dose hydroxy safflower yellow A or its medically-acceptable salt application for preparing medicine for cerebral apoplexy induced from being ischemic | |
CN107550923A (en) | A kind of pharmaceutical composition for treating cardiovascular and cerebrovascular disease and its application and the injection formed by its preparation | |
CN1073848C (en) | High content ginko leaves flavone lactone extract and its prepn. method | |
CN105494757A (en) | Pure natural functional drink suitable for patient with chronic hepatitis B and preparation method thereof | |
CN112494502B (en) | Saccharide composition for replenishing blood in blood deficiency syndrome | |
CN1935178A (en) | Ginkgo leaf extract and barrenwort extract composition | |
JP4718443B2 (en) | Radixnotoginshen saponin family intravenous injection and method for its preparation | |
CN107569505A (en) | A kind of pharmaceutical composition for treating myocardial ischemia and its application and the injection formed by its preparation | |
CN101716253B (en) | Chinese medicinal preparation containing panax notoginseng, and preparation method thereof | |
CN1736434A (en) | Throat comforting medicine with licorice and preparation process thereof | |
KR20010009653A (en) | Composition for treating sexual dysfunction | |
CN106344634B (en) | A kind of mango bark extract and its preparation method and application | |
CN104587047B (en) | A kind of Chinese medicine composition for being used to treat cardiovascular and cerebrovascular disease | |
CN1899352B (en) | Chinese medicine effective part composition for supplementing qi and recovering pulse | |
CN100415241C (en) | Medicinal composition for treating cardio-cerebrovascular diseases |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20200731 Address after: No.8, Industrial Avenue, furniture base, Longling Industrial Park, Nankang District, Ganzhou City, Jiangxi Province Applicant after: LONCH GROUP JIANGXI PHARMACEUTICAL Co.,Ltd. Address before: 044200, No. 99, Xinjian South Road, Wanrong County, Yuncheng, Shanxi Applicant before: LONCH GROUP WANRONG PHARMACEUTICAL Co.,Ltd. |
|
TA01 | Transfer of patent application right | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180112 |
|
RJ01 | Rejection of invention patent application after publication |