CN101428091A - Uses of medicament in preparing medicament for inhibiting of peroxide - Google Patents
Uses of medicament in preparing medicament for inhibiting of peroxide Download PDFInfo
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Abstract
The invention relates to the application of a medication for preparing a medication for inhibiting peroxide. The medication is prepared by the following raw medicinal herbs according to the weight percent: 4 to 9 percent of Chinese angelica, 4 to 9 percent of chuanxiong rhizome, 2 to 8 percent of white peony root, 2 to 8 percent of prepared rehmannia root, 10 to 15 percent of rhynohophylla, 10 to 15 percent of spatholobus stem, 10 to 15 percent of selfheal spike, 10 to 15 percent of cassia seed, 10 to 15 percent of nacre, 4 to 9 percent of rhizoma corydalis and 0.5 to 2 percent of asarum herb.
Description
Technical field
The present invention relates to the field of Chinese medicines, be specifically related to the application of a kind of Chinese medicine in the medicine of preparation inhibition peroxide.
Background technology
A lot of lysises all can cause the generation of peroxide.For example, behind the ischemia-reperfusion, vascular endothelial cell produces negative oxygen anion by hypoxanthine and xanthine dehydrogenase, and then, negative oxygen anion converts hydrogen peroxide under the catalysis of SOD, a part of hydrogen peroxide generates hydroxyl radical free radical by the Haber-Weiss reaction.Hydrogen peroxide, peroxide such as hydroxyl radical free radical both can lipid peroxidations, and dna breakage equivalent damage vascular endothelial cell and basement membrane of blood vessel cell can activate NF-κ B again, induce select plain, the release of adhesion molecule and inflammatory molecule.The generation that suppresses peroxide is to improve the key link of perfusion back microcirculation disturbance again.
A kind of medicine of the present invention [patent No.: 93100050.5] is made up of Radix Angelicae Sinensis, Rhizoma Chuanxiong etc.It is under the guidance of motherland's theory of medicine, and sums up through clinical practice for many years and to form, and has the effect of the headache that the treatment internal injury causes, is applicable to symptoms such as dizziness that angioneurotic headache, migraine and hypertension causes, headache clinically.In this prescription ratio, can make any dosage form on the pharmaceutics.Granule dosage form is wherein produced by Tianjin Tasly Pharmaceutical Co., Ltd, and name is called " blood-nourishing and brain-refreshing granules "." function with cure mainly " got permission is the suppressing the hyperactive liver that nourishes blood, promoting blood circulation to remove obstruction in the collateral.Be used for various headaches, traumatic cranial nerve syndrome due to the blood deficiency and excessive liver-YANG, stagger, susceptible to lose temper due to restlessness, insomnia and dreamful sleep etc.Be mainly used in the headache due to treatment blood deficiency, blood stasis, the hyperactivity of YANG due to deficiency of YIN clinically.Because its definite curative effect since listing, has won the trust of extensive patients.
Research had in the past proved the Main Ingredients and Appearance paeoniflorin of the Radix Paeoniae Alba in the blood-nourishing and brain-refreshing granules, the Main Ingredients and Appearance ligustrazine of Rhizoma Chuanxiong, and the Main Ingredients and Appearance ferulic acid of Radix Angelicae Sinensis, the Main Ingredients and Appearance rehmannioside of Radix Rehmanniae Preparata is in the external effect that has the inhibition peroxide to produce.But whether the compound Chinese medicinal preparation blood-nourishing and brain-refreshing granules that contains mentioned component has the effect that suppresses peroxide, particularly whether has the effect that suppresses peroxide etc. in vivo and does not appear in the newspapers as yet.
Summary of the invention
The present invention is on the basis of existing Chinese patent (patent No. is 93100050.5), the new purposes invention of finishing, and the composition of prescription is as follows by weight ratio:
Radix Angelicae Sinensis 4～9%, Rhizoma Chuanxiong 4～9%, the Radix Paeoniae Alba 2～8%, Radix Rehmanniae Preparata 2～8%, Ramulus Uncariae Cum Uncis 10～15%, Caulis Spatholobi 10～15%, Spica Prunellae 10～15%, Semen Cassiae 10～15%, Concha Margaritifera 10～15%, Rhizoma Corydalis 4～9%, Herba Asari 0.5～2%;
Best proportioning is:
Radix Angelicae Sinensis 6.75%, Rhizoma Chuanxiong 6.75%, the Radix Paeoniae Alba 5.4%, Radix Rehmanniae Preparata 5.4%, Ramulus Uncariae Cum Uncis 13.5%, Caulis Spatholobi 13.5%, Spica Prunellae 13.5%, Semen Cassiae 13.5%, Concha Margaritifera 13.5%, Rhizoma Corydalis 6.75%, Herba Asari 1.34%.
This patent drug compositions is implemented by following scheme:
Get raw medicinal herbs according to the above ratio, extracting in water 3 times, each 1 hour; Merge extractive liquid, concentrates, and adds the ethanol of 2 times of its weight, staticly settles; Get supernatant, be condensed into extractum, relative density is 1.3～1.4, and paste-forming rate is 10%; Add acceptable auxiliary on the medicament, make pharmaceutically acceptable dosage form according to the process of routine.It is 24 hours that the wherein said time of leaving standstill is preferably.Acceptable auxiliary is preferably sucrose and dextrin on the medicament, and preferred proportion is extractum, sucrose and the dextrin weight ratio by 1:3:1, makes granule according to the process of routine.
Pharmaceutical composition of the present invention has the effect of the headache that causes of treatment internal injury, is applicable to symptoms such as dizziness that angioneurotic headache, migraine and hypertension causes, headache clinically.
Through clinical experimental research in recent years, the applicant has also found effects such as pharmaceutical composition cerebral blood flow increasing of the present invention, treatment apoplexy sequela, can also microcirculation improvement obstacle and prevention of brain apoplexy.But also there is not bibliographical information to be used to suppress the generation of peroxide.
Be example with mongolian gerbil brain thin vein below, investigated pharmaceutical composition of the present invention and suppressed the purposes that peroxide produces.
The medicine of using in the experiment is granule dosage form---the blood-nourishing and brain-refreshing granules of medicine of the present invention.Specifically studied blood-nourishing and brain-refreshing granules to ischemia-reperfusion after the influence that produces of mongolian gerbil brain thin vein wall peroxide.
1. materials and methods
(1) animal
Mongolian gerbils, male, body weight 65～90g purchases the laboratory animal portion in the Capital University of Medical Sciences, the quality certification number: SCXK (capital) 2000-0012.In Department Of Medicine, Peking University's animal center, handle regulation by the Department Of Medicine, Peking University laboratory animal, ad lib drinking-water, single cage is raised, 22 ℃ of temperature, relative humidity switched lamp source (morning turn on light) in 40%, 12 hour at 7.
(2) trial drug
Trial drug (blood-nourishing and brain-refreshing granules) is the granule of making according to the method for the embodiment of the invention 2, is mixed with the aqueous solution of 80mg/ml and 160mg/ml before the experiment.
(3) chemical reagent
(Dihydrorhodamine 123 for dihydro Luo Da bright 123, DHR 123) buy Eugene company in the U.S., marked by fluorescein isothiocyanate albumin (FITC-albumin) is bought the SIGMA company in the U.S., Luo Daming 6G perchlorate (Rhodamine6G perchlorate) is bought the FLUKA company in the U.S., and urethane (Urethane) is bought in Chinese Shanghai sky lotus Fine Chemical Co., Ltd.
(4) animal model
Get 20% urethane, press the consumption of 2.0g/kg.bw, through the intraperitoneal injection of anesthesia mongolian gerbils.In cervical region medisection, separate trachea, connect toy respirator (ALC-V8), keep mechanical ventilation in whole observation process.The closer of particular design (a thin polyethylene catheter and the lasso trick that thick plastic tube is formed) is placed on bilateral common carotid arteries and does not influence blood flow.Expose femoral vein, inserting and keeping somewhere diameter is the polyethylene catheter of 5mm.Cut the brain fur, be drilled in the cranium window of opening one 3 * 3mm before bregma with portable cranium.37 ℃ artificial cerebrospinal fluids are dripped on the cranium window continuously to keep the brain surface moistening.With being connected in fluorescence video camera (C7190, HAMAMATSU, upright biological microscope (DMLFS Japan), LEICA, Germany), select diameter at 30-50 μ m, the long thin vein that does not have obvious bending of 200 μ m with 10 times of object lens, (J2118A is observed on the basis on monitor, TCL, Huizhou is China) after 10 minutes, close rope mongolian gerbils bilateral carotid arteries (ischemia), remove after 30 minutes and close rope (perfusion again).Observe continuously and (DVR-R25, Malata China) write down microcirculation dynamic 60 minutes with being connected in fluorescence video camera CD writer.Sham operated rats is not closed the rope bilateral carotid arteries, and other operate same ischemia-reperfusion group.Blood-nourishing and brain-refreshing granules 0.4g/kg+ ischemia-reperfusion group, a blood-nourishing and brain-refreshing 0.8g/kg+ ischemia-reperfusion group, with irritating stomach tube, are irritated stomach and are given blood-nourishing and brain-refreshing granules aqueous solution 0.4g/kg.bw and 0.8g/kg.bw respectively before 90 minutes at ischemia-reperfusion.
(5) thin vein wall peroxide produces dynamic measurement
Observed preceding 10 minutes on the basis, with the peroxide fluorescent probe dihydro Luo Da bright 123 continuous surfaces that drip at the brain look-out station of 10umol/ml concentration.When peroxide and DHR meet, DHR can be reduced into rhodamine 123, observe and note down luminous site and the intensity (excitation wavelength 510nm, emission wavelength 534nm) of DHR with the hypersensitization video camera that is connected in biological microscope (Hamamatsu EB-CCD Camera C7190 Japan).In order to measure the difference of blood vessel endothelium histofluorescence intensity, measure the average fluorescent strength of intravascular space and blood vessel wall with image analysis software Image-Pro plus 5.0.Measure the average fluorescent strength of each intravascular space and blood vessel wall, their difference (DI) has been reacted the oxidized degree of DHR.Before the measurement ischemia (Ibase), and fluorescence intensity difference (Ix) in perfusion beginning 0 minute, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 60 timesharing thin vein walls and the blood vessel again, with the numerical value before the ischemia is basic value, represent the variation of DHR fluorescence intensity with the value (Ix) of each time and the ratio of basic value (Ibase), dynamic with the generation of judging thin vein wall peroxide.
(6) statistics
All numerical value are represented with meansigma methods ± standard error.Data analysis is handled with one factor analysis of variance one-way analysis ofvariance (ANOVA) and Fisher s post Hoc test check.If p＜0.05 is a significant difference.
2. result
Blood-nourishing and brain-refreshing granules to ischemia-reperfusion after the influence of mongolian gerbil brain thin vein wall DHR fluorescence intensity.
As seen from Figure 1, ischemia-reperfusion mongolian gerbil (a) and blood-nourishing and brain-refreshing granules+ischemia-reperfusion group mongolian gerbil (c) is not observed thin vein wall DHR fluorescence radiation position before ischemia.Pour into 60 timesharing again, can observe the ischemia-reperfusion mongolian gerbil along the brain thin vein wall enhanced position of DHR fluorescence intensity (b), and blood-nourishing and brain-refreshing granules+ischemia-reperfusion group mongolian gerbil is not being observed the enhancing (d) of brain thin vein wall DHR fluorescence intensity.
As seen from Figure 2, the DHR fluorescence intensity ratio of sham operated rats mongolian gerbil brain thin vein wall does not almost change in this viewing duration.The DHR fluorescence intensity ratio of ischemia-reperfusion group mongolian gerbil cerebral veins, venae cerebri wall begins to increase after pouring into 10 fens again, and continues to increase.Blood-nourishing and brain-refreshing granules 0.4g/kg+ ischemia-reperfusion group and blood-nourishing and brain-refreshing granules 0.8g/kg+ ischemia-reperfusion group have suppressed the increase of the DHR fluorescence intensity of the brain thin vein wall that ischemia-reperfusion causes significantly after pouring into 10 minutes again.
Change into bright 123 (rhodamine 123) of Luo Da after the peroxide reactions such as DHR and hydrogen peroxide, Luo Da bright 123 can enter in the cell, is combined on the DNA mitochondrial DNA film, can observe reacted luminous site of DHR and fluorescence intensity with fluorescence microscope.The generation of measuring mesentery thin vein wall peroxide with this method is dynamic.The pre-administration that the present invention has observed directly blood-nourishing and brain-refreshing granules with this method can suppress the generation of gerbil jird cerebral cortex thin vein wall peroxide behind the ischemia-reperfusion.Further the proof blood-nourishing and brain-refreshing granules can be protected cerebrovascular endothelial cell, improves brain microcirculation.
Pharmaceutical composition of the present invention can be oral or be taken after mixing it with water, or by other conventional medication administrations.Every day, consumption was for being equivalent to 5～20g raw medicinal herbs weight.
Through a large amount of discovering, pharmaceutical composition of the present invention can suppress peroxide significantly and produce, thereby to having potential therapeutic value because peroxide produces the relevant disease that causes.
Description of drawings
Fig. 1 is a sham operated rats, the continuous variation of ischemia-reperfusion group, blood-nourishing and brain-refreshing granules 0.4g/kg+ ischemia-reperfusion group, blood-nourishing and brain-refreshing granules 0.8g/kg+ ischemia-reperfusion group mongolian gerbil brain thin vein wall DHR fluorescence intensity before ischemia and after pouring into again.
Data are every group of 6 gerbil jird meansigma methods ± standard errors.* P＜0.05vs basic value; # P＜0.05vs ischemia-reperfusion group.
The specific embodiment
The pharmaceutical composition that further specifies among the present invention below by concrete embodiment suppresses application in the medicine that peroxide produces in preparation, but not as limitation of the present invention.
Embodiment 1
(1) gets Radix Angelicae Sinensis 80g, Rhizoma Chuanxiong 80g, Radix Paeoniae Alba 80g, Radix Rehmanniae Preparata 80g, Ramulus Uncariae Cum Uncis 120g, Caulis Spatholobi 120g, Spica Prunellae 120g, Semen Cassiae 120g, Concha Margaritifera 120g, Rhizoma Corydalis 70g, Herba Asari 10g;
(2) with above-mentioned medical material extracting in water 3 times, each 1 hour, merge extractive liquid,, suitably concentrate, add the ethanol of 2 times of amounts, leave standstill 24 hours precipitations, get supernatant concentration and become extractum, relative density is 1.3, and paste-forming rate is 10%, gets extractum, sucrose and dextrin and makes 200 in tablet by the part by weight of 1:3:1.
Embodiment 2
(1) gets Radix Angelicae Sinensis 67.5g, Rhizoma Chuanxiong 67.5g, Radix Paeoniae Alba 54g, Radix Rehmanniae Preparata 54g, Ramulus Uncariae Cum Uncis 135g, Caulis Spatholobi 135g, Spica Prunellae 135g, Semen Cassiae 135g, Concha Margaritifera 135g, Rhizoma Corydalis 67.5g, Herba Asari 13.4g;
(2) with above-mentioned medical material extracting in water 3 times, each 1 hour, merge extractive liquid,, suitably concentrate, add the ethanol of 2 times of amounts, leave standstill 24 hours precipitations, get supernatant concentration and become extractum, relative density is 1.4, and paste-forming rate is 10%, gets extractum, sucrose and dextrin and makes 125 bags of granules by the part by weight of 1:3:1.
Claims (8)
1. the application of pharmaceutical composition in the medicine of preparation inhibition peroxide, this medicine is made by the raw medicinal herbs of following weight percentage:
Radix Angelicae Sinensis 4～9%, Rhizoma Chuanxiong 4～9%, the Radix Paeoniae Alba 2～8%, Radix Rehmanniae Preparata 2～8%, Ramulus Uncariae Cum Uncis 10～15%, Caulis Spatholobi 10～15%, Spica Prunellae 10～15%, Semen Cassiae 10～15%, Concha Margaritifera 10～15%, Rhizoma Corydalis 4～9%, Herba Asari 0.5～2%.
2. the described application of claim 1 is characterized in that the generation of described peroxide is caused by ischemia-reperfusion.
3. the described application of claim 2 is characterized in that peroxide results from the thin vein blood vessel endothelium.
4. the described application of claim 1 is characterized in that described pharmaceutical composition made by the raw medicinal herbs of following weight percentage:
Radix Angelicae Sinensis 6.75%, Rhizoma Chuanxiong 6.75%, the Radix Paeoniae Alba 5.4%, Radix Rehmanniae Preparata 5.4%, Ramulus Uncariae Cum Uncis 13.5%, Caulis Spatholobi 13.5%, Spica Prunellae 13.5%, Semen Cassiae 13.5%, Concha Margaritifera 13.5%, Rhizoma Corydalis 6.75%, Herba Asari 1.34%.
5. any described application of claim 1-4 is characterized in that described pharmaceutical composition prepares according to following method:
Get raw medicinal herbs in proportion, extracting in water 3 times, each 1 hour; Merge extractive liquid, concentrates, and adds the ethanol of 2 times of its weight, staticly settles; Get supernatant, be condensed into extractum, relative density is 1.3～1.4; Add acceptable auxiliary on the medicament, make preparation.
6. the described application of claim 5 is characterized in that the described time of leaving standstill is 24 hours.
7. the described application of claim 5 is characterized in that acceptable auxiliary is sucrose and dextrin on the medicament.
8. the described application of claim 7 is characterized in that extractum, sucrose and the dextrin weight ratio by 1:3:1, makes granule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101500692A CN101428091A (en) | 2007-11-06 | 2007-11-06 | Uses of medicament in preparing medicament for inhibiting of peroxide |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101500692A CN101428091A (en) | 2007-11-06 | 2007-11-06 | Uses of medicament in preparing medicament for inhibiting of peroxide |
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| CN101428091A true CN101428091A (en) | 2009-05-13 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102998375A (en) * | 2011-09-13 | 2013-03-27 | 天士力制药集团股份有限公司 | Method for simultaneously detecting contents of ferulic acid and paeoniflorin in blood nourishing and brain arousing particle |
| JP2016503040A (en) * | 2012-12-21 | 2016-02-01 | タスリー・ファーマシューティカル・グループ・カンパニー・リミテッドＴａｓｌｙ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｇｒｏｕｐ Ｃｏ．， Ｌｔｄ． | Pharmaceutical composition for treating headache and method for preparing the same |
-
2007
- 2007-11-06 CN CNA2007101500692A patent/CN101428091A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102998375A (en) * | 2011-09-13 | 2013-03-27 | 天士力制药集团股份有限公司 | Method for simultaneously detecting contents of ferulic acid and paeoniflorin in blood nourishing and brain arousing particle |
| CN102998375B (en) * | 2011-09-13 | 2016-04-20 | 天士力制药集团股份有限公司 | A kind of method simultaneously detecting forulic acid and paeoniflorin content in blood-nourishing and brain-refreshing granules |
| JP2016503040A (en) * | 2012-12-21 | 2016-02-01 | タスリー・ファーマシューティカル・グループ・カンパニー・リミテッドＴａｓｌｙ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｇｒｏｕｐ Ｃｏ．， Ｌｔｄ． | Pharmaceutical composition for treating headache and method for preparing the same |
| US9795648B2 (en) | 2012-12-21 | 2017-10-24 | Tasly Pharmaceutical Group Co., Ltd. | Pharmaceutical composition for treating headache, and preparation method thereof |
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Application publication date: 20090513 |