CN102688184A - Preparation method of ephedrine hydrochloride injection for improving rat blood rheological obstacle - Google Patents
Preparation method of ephedrine hydrochloride injection for improving rat blood rheological obstacle Download PDFInfo
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- CN102688184A CN102688184A CN2012101514037A CN201210151403A CN102688184A CN 102688184 A CN102688184 A CN 102688184A CN 2012101514037 A CN2012101514037 A CN 2012101514037A CN 201210151403 A CN201210151403 A CN 201210151403A CN 102688184 A CN102688184 A CN 102688184A
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Abstract
A preparation method of ephedrine hydrochloride injection for improving rat blood rheological obstacle belongs to the field of preparation of drugs for improving biological blood disorders. The preparation method is characterized in that active ingredients of sedanolideat least 98% in purity, gastrodin at least 98% in purity and ephedrine hydrochloride at least 98% in purity are proportionally mixed in 5% tween-80 aqueous solution to make the ephedrine hydrochloride injection, and a combination of the sedanolide, the gastrodin and the ephedrine hydrochloride is 5 mg/l in concentration in the 5% tween-80 aqueous solution. Compared with clinically common drug nimodipine, the ephedrine hydrochloride injection has evidently improved blood viscosity, maximum deformation index of erythrocytes, maximum aggregation index of the erythrocytes and aggregation rate of platelets.
Description
Technical field
Improve the method for preparing of the injection that contains ephedrine that the hemorheology obstacle uses, belong to the manufacturing technology field that prevents and treats brain ischemia medicament.
Background technology
Application number is 200880001478.9; The Chinese invention patent of " a kind of pharmaceutical composition of preventing and treating the cerebral ischemia apoplexy and preparation method thereof " by name has been pointed out a kind of pharmaceutical composition that is used to prevent and treat cerebral infarction, is together to form by sedanolide, ligustilide and gastrodine.Wherein, gastrodine is that purity is the above commercially available prod of 98 %, and the purity of sedanolide and ligustilide has correspondingly proposed purity and be 99.17% sedanolide and purity and be the method for preparing of 98.32% ligustilide all more than 98 %.Its experimental result shows that the compatibility of these three kinds of compositions can reduce the degree of scope of ischemic brain infarction (showing with the cerebral infarction percentage table) and hemiplegia of limb (representing with the behavior symptom scoring) effectively.During promptly as injection treatment administration, the rat cerebral infarction area percentage is between 13.03%-18.58 %; Behavior scoring is between 1.50 minutes-2.30 minutes; During as oral agents prevention administration, the rat cerebral infarction area percentage is between 21.36%-21.67%, and behavior scoring is between 3.36 minutes-4.33 minutes.Its drug effect is better than clinical application MAILUONING (injection) commonly used and ligustrazine (injection and oral agents).Improve the health microcirculation experimental data of (representing) but lack with hemorheology index.
In the document that retrieves at present, do not find to have in the pharmaceutical composition and adopt ephedrine, gastrodine and sedanolide to come compatibility.
Summary of the invention
The objective of the invention is to extract and prepare a kind of to improving the injection preparation that contains ephedrine that the hemorheology obstacle is used.
The present invention is a kind of method for preparing of improving the injection that contains ephedrine that the hemorheology obstacle uses:
One of its characteristic; Taking by weighing purity is at least 98% sedanolide 0.16g, purity and is at least 98% gastrodine 0.024g, purity and is at least 98% ephedrine 0.24g; In percent by volume 5% Tween-81 85ml; Stir, the compositions that makes described sedanolide, gastrodine and ephedrine is that concentration in 5% the Tween-81 aqueous solution is 5mg/ml in percent by volume.
Two of its characteristic; Taking by weighing purity is at least 98% sedanolide 0.16g, purity and is at least 98% gastrodine 0.01g, purity and is at least 98% ephedrine 0.24g; The adding percent by volume is 5% Tween-81 82ml; Stir, the compositions that makes described sedanolide, gastrodine and ephedrine is that concentration in 5% the Tween-81 aqueous solution is 5mg/ml in percent by volume.
Experiment showed, that above-mentioned two kinds are tried thing and all can improve hemorheology index, thus the performance treating cerebral ischemia.Suitable with the clinical application nimotop.Wherein embodiment 1 is better than embodiment 2.
The specific embodiment
One, being tried thing prepares:
Embodiment 1: the sedanolide 0.16g that takes by weighing 98% purity; The gastrodine 0.024g of 98% purity; The ephedrine 0.24g of 98% purity; The adding percent by volume is 5% Tween-81 85ml, stirs, and making the concentration of compositions in the Tween-81 aqueous solution of 5% (volume ratio) of described sedanolide, gastrodine and ephedrine is 5mg/ml.
Embodiment 2: the sedanolide 0.16g that takes by weighing 98% purity; The gastrodine 0.01g of 98% purity; The ephedrine 0.24g of 98% purity; The adding percent by volume is 5% Tween-81 82ml, stirs, and making the concentration of compositions in the Tween-81 aqueous solution of 5% (volume ratio) of described sedanolide, gastrodine and ephedrine is 5mg/ml.
Described sedanolide is prepared by the described method of application for a patent for invention that application number 200880001478.9, name are called a kind of pharmaceutical composition of preventing and treating the cerebral ischemia apoplexy and preparation method thereof, and gastrodine and ephedrine are the commercially available prod.
Two, test method:
Experiment is accomplished by Xuanwu Hospital of Capital University of Medical Science.
Model is made: with 25% urethane, 1.5 g/kg intraperitoneal injection of anesthesia, at rat parietal bone of head position, the bregma center is 2mm forward with rat in experiment; 2.5mm place to the right; Make a call to the bone window of the about 2mm of a diameter with dental burr, measurement electrode is inserted 2mm under the pia mater encephali, measure cerebral tissue blood flow (rCBF) before the ligation; Ligation bilateral common carotid arteries then, rCBF when measuring 10min after the ligation, 60min and 120min respectively.Blood flow is in ml/100g/min.And calculating relative blood flow amount.Detect principle and remove method according to hydrogen.
Before laboratory animal was put to death, through abdominal aortic blood 0.8ml, anticoagulant detected with blood viscosity instrument, cuts (200S with height
-1), in cut (30 S
-1) and low (5 S that cut
-1) time blood viscosity represent WBV (seeing table 1); Other gets anticoagulation and leaves heart 8min with 2000, and its supernatant is blood plasma, gets 0.8m1 blood plasma and tests 100 S with blood viscosity instrument
-1The time plasma viscosity (seeing table 2).With erythrocyte maximum distortion index (MAXDI) expression RCD (seeing table 3); With the maximum aggregate index of erythrocyte (MAXD) expression erythrocyte aggregation (seeing table 3).
The preparation of middle cerebral artery thrombus model: the method improvement by Tamura etc. forms.Laboratory animal adopts 350g ± 20g SD rat, with chloral hydrate 0.35g/kg intraperitoneal injection of anesthesia.The rat RAR is fixed; Curved incision at paropia and external auditory meatus line mid point work one long 1.5cm exposes temporal bone, makes the bone window of a diameter 2.5mm to nasal side 1mm place at cheekbone and temporo squamosum joint with dental burr; Expose middle cerebral artery, suction is had 10 μ, 1 50% FeCl
3The small pieces filter paper of liquid applies on middle cerebral artery, and operation is carried out under stereomicroscope.Treat middle cerebral artery blackening behind the 30min, take off filter paper, use the normal saline flushing local organization, layer-by-layer suture.Sham operated rats is not applied FeCl
3, surplus same model group.
Experiment is divided into groups: laboratory animal adopts the SD rat, and body weight is 350 ± 20g.Experiment is divided into 5 groups: blank group and model control group give normal saline, and dosage is the 0.04ml/100g body weight; Positive control drug is 0.02% sterile solution for injection of clinical treatment cerebral ischemia medicine nimotop commonly used, is produced lot number CBWLL11B by Bayer A.G.Dosage is 8 μ g/100g, and dosage is the 0.04ml/100g body weight; 1 group of embodiment, 2 groups of embodiment, dosage is 0.16ml/100g body weight.
Medication: embodiment 1, nimotop 1h sublingual vein drug administration by injection 3 times altogether after 10 min, the modeling before modeling, after the modeling; The prevention administration is 3 before embodiment 2 arts, every day 1 time, and 0.5h modeling after the last administration, the postoperative medication is with embodiment 1.
The experimental data statistics adopts (
± SD) expression of mean ± standard deviation.Experimental result relatively, is carried out the t check through between group.The result is with the p value representation.Mean is the average between one group of data of expression.Standard deviation is the index of one group of data discrete degree of expression.The t check is that the significance of regression parameter is tested, and the p value is the declining indicator of credible result degree.< 0.05 for having significant difference between group, and < 0.01 for having significant differences between group for P for P.
Three, drug effect:
Two embodiment all can improve hemorheology index.For example, the RCD that can raise reduces erythrocyte aggregation, reduces platelet aggregation rate.Can reduce WBV and plasma viscosity.Prompting is one of mechanism of its treating cerebral ischemia to hemorheological improvement effect.Wherein embodiment 1 is better than embodiment 2.Performance (sees table 1-3 for details) as follows:
1. after rat forms the middle cerebral artery thrombosis, can cause that RCD reduces, erythrocyte aggregation raises, and platelet aggregation rate raises, and (height is cut 200S to WBV
-1, in cut 30 S
-1With low 5 S that cut
-1) and plasma viscosity (100 S
-1) all increase to some extent than normal group, the variation that hemorheology is is sticking, dense, coagulate, gather state is described in the generating process of cerebral ischemia.
2. 1 pair of 24 hours middle cerebral artery thrombus model Mus blood viscosity of embodiment and hemorheological improvement effect are better than embodiment 2, and on following index, have significant difference:
24h whole blood reduced viscosity (height is cut): embodiment is starkly lower than 2 groups of embodiment for 1 group, and P < 0.05; 24h whole blood reduced viscosity (low cutting): embodiment is starkly lower than 2 groups of embodiment for 1 group, and P < 0.05.
Table 1. is tried the influence (
± SD) of thing to 24h middle cerebral artery thrombus model blood viscosity
Annotate: each group is compared * P < 0.05 with model group; * P < 0.01
Table 2. is tried the influence (
± SD) of thing to 48h middle cerebral artery thrombus model blood viscosity
Annotate: each group is compared * P < 0.05 with model group; * P < 0.01; Embodiment 1 compares with embodiment 2, # P < 0.05
Table 3. is tried thing to hemorheological influence of 24h middle cerebral artery thrombus model (
± SD)
Annotate: each group is all compared * P < 0.05 with model group; * P < 0.01; 1 group of embodiment compares # P < 0.05 for 2 groups with embodiment.
Claims (2)
1. improve the method for preparing that contains the ephedrine injection of rat blood rheology obstacle, it is characterized in that,
Taking by weighing purity is at least 98% sedanolide 0.16g, purity and is at least 98% gastrodine 0.024g, purity and is at least 98% ephedrine 0.24g; Be added in percent by volume and be among 5% the Tween-81 85ml; Stir, the compositions that makes described sedanolide, gastrodine and ephedrine is that concentration in 5% the Tween-81 aqueous solution is 5mg/ml in percent by volume.
2. that improves rat blood rheology obstacle contains the ephedrine injection preparation, it is characterized in that,
Taking by weighing purity is at least 98% sedanolide 0.16g, purity and is at least 98% gastrodine 0.01g, purity and is at least among 98% the ephedrine 0.24g; In percent by volume is 5% Tween-81 82ml; Stir, the compositions that makes described sedanolide, gastrodine and ephedrine is that concentration in 5% the Tween-81 aqueous solution is 5mg/ml in percent by volume.
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|---|---|---|---|
| CN 201210151403 CN102688184B (en) | 2012-05-15 | 2012-05-15 | Preparation method of ephedrine hydrochloride injection for improving rat blood rheological obstacle |
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| CN 201210151403 CN102688184B (en) | 2012-05-15 | 2012-05-15 | Preparation method of ephedrine hydrochloride injection for improving rat blood rheological obstacle |
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| CN102688184B CN102688184B (en) | 2013-10-16 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10869845B1 (en) | 2020-01-22 | 2020-12-22 | Nevakar Inc. | Ephedrine compositions and methods |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101115492A (en) * | 2005-02-04 | 2008-01-30 | 帝斯曼知识产权资产管理有限公司 | Novel composition comprising ligustilide and process for their manufacture |
| WO2009100587A1 (en) * | 2008-02-14 | 2009-08-20 | Tsinghua University | A drug composition for treatment and prevention of ischemic stroke and its preparation methods |
-
2012
- 2012-05-15 CN CN 201210151403 patent/CN102688184B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101115492A (en) * | 2005-02-04 | 2008-01-30 | 帝斯曼知识产权资产管理有限公司 | Novel composition comprising ligustilide and process for their manufacture |
| WO2009100587A1 (en) * | 2008-02-14 | 2009-08-20 | Tsinghua University | A drug composition for treatment and prevention of ischemic stroke and its preparation methods |
Non-Patent Citations (1)
| Title |
|---|
| 赵晓科等: "麻黄碱促进脑缺血大鼠运动功能康复的细胞及分子机制", 《第四军医大学学报》, vol. 28, no. 3, 31 December 2007 (2007-12-31) * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10869845B1 (en) | 2020-01-22 | 2020-12-22 | Nevakar Inc. | Ephedrine compositions and methods |
| WO2021150253A1 (en) * | 2020-01-22 | 2021-07-29 | Nevakar Inc. | Ephedrine compositions and methods |
| US11491121B2 (en) | 2020-01-22 | 2022-11-08 | Nevakar Injectables Inc. | Ephedrine compositions and methods |
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|---|---|
| CN102688184B (en) | 2013-10-16 |
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