CN104434943A - Pharmaceutical composition for treating cerebral stroke and cerebral stroke caused depression - Google Patents
Pharmaceutical composition for treating cerebral stroke and cerebral stroke caused depression Download PDFInfo
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- CN104434943A CN104434943A CN201410798222.2A CN201410798222A CN104434943A CN 104434943 A CN104434943 A CN 104434943A CN 201410798222 A CN201410798222 A CN 201410798222A CN 104434943 A CN104434943 A CN 104434943A
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- pharmaceutical composition
- troxerutin
- ting
- chlorine
- plantagoside
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- LFBGHOZNSIRARQ-UHFFFAOYSA-N CC(c(c(C)c1)ccc1OC(CCNC)c1ccccc1)(F)F Chemical compound CC(c(c(C)c1)ccc1OC(CCNC)c1ccccc1)(F)F LFBGHOZNSIRARQ-UHFFFAOYSA-N 0.000 description 1
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
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- Life Sciences & Earth Sciences (AREA)
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- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of pharmaceuticals and particularly relates to a pharmaceutical composition for treating cerebral stroke and cerebral stroke caused depression. The pharmaceutical composition is prepared from chlorxetine and troxerutin, wherein the weight percent of chlorxetine is 1-99%, and the weight percent of troxerutin is 1-99%. The pharmaceutical composition can also contain plantagoside, wherein the weight percent of chlorxetine is 1-98%, the weight percent of troxerutin is 1-98%, and the weight percent of plantagoside is 1-98%. The composition disclosed by the invention not only has a relatively good cerebral stroke treating effect, but also has a better synergetic effect in the aspect of treating the cerebral stroke caused depression.
Description
Technical field
The invention belongs to drug world, be specifically related to a kind of pharmaceutical composition being used for the treatment of the depression that apoplexy and apoplexy cause.
Background technology
Cerebral infarction also known as cerebral infarction, be make brain tissue ischemia by cerebral blood supply obstacle, anoxia causes cerebral malacia, is clinical refractory disease.The cause of disease is topmost is hypertension, cerebral arteriosclerosis, acute hypotension, arteritis and hematopathy, wound etc., but turns to most important with hypertension and Atherosclerosis.Apoplexy is one of three large reasons of human death, and cerebral infarction accounts for whole apoplexy 43%-65%.Its incidence and mortality is high far beyond other apoplexy.
Post-stroke depression (post-stroke depression, PSD) is a kind of organic affective disorder, is one of modal complication of apoplexy, and usual onset is slow, and the course of disease is delayed, and harm is serious, but pathogenesis it be unclear that.It has been generally acknowledged that, in brain, monoaminergic nerve hypofunction is the pathophysiological basis forming Post-Cerebral Hemorrhage Depression.Wider antidepressant is used at present to be that the property selected 5-hydroxy tryptamine returns and draws blocker clinically, comprise fluoxetine, color removes woods, paroxetine etc., but due to well-known reason, some untoward reaction of gastrointestinal after its medication, as Nausea and vomiting, anorexia, diarrhoea, and its liver poison, kidney toxic and side effects, thus limit the application clinically of these medicines.
Fluoxetine is the reuptake inhibitor of a kind of selectivity five hydroxytryptamine, optionally suppresses the re uptake after the release of central nervous system's presynaptic five hydroxytryptamine, thus improves the concentration of synaptic space five hydroxytryptamine, produce obvious antidepressant effects.Because it is very little on the impact of other neurotransmitteies, therefore sedation be there is no to animal and human's brain.Abroad, this medicine has been widely used in the clinical treatment of depression; The concrete structure formula of chlorine Xi Ting is as follows:
Summary of the invention
An object of the present invention is to provide a kind of pharmaceutical composition, it is made up of chlorine Xi Ting and troxerutin, and wherein the percentage by weight of the two is the troxerutin of chlorine Xi Ting and 1-99% of 1-99%.More specifically, the percentage by weight of chlorine Xi Ting and troxerutin can be the troxerutin of chlorine Xi Ting and 20-80% of 20-80%, the troxerutin of chlorine Xi Ting and 40-80% of 20-60%, or the troxerutin of chlorine Xi Ting and 55-75% of 25-45%.
In one embodiment of the invention, can also comprise Plantagoside in described pharmaceutical composition, the percentage by weight of described chlorine Xi Ting, troxerutin and Plantagoside is the troxerutin of chlorine Xi Ting, 1-98% and the Plantagoside of 1-98% of 1-98%.
More specifically, the percentage by weight of chlorine Xi Ting, troxerutin and Plantagoside can be the troxerutin of chlorine Xi Ting, 5-90% and the Plantagoside of 5-90% of 5-90%;
Or the troxerutin of chlorine Xi Ting, 10-80% of 10-80% and the Plantagoside of 10-80%;
Or the troxerutin of chlorine Xi Ting, 15-70% of 15-70% and the Plantagoside of 15-70%;
Or the troxerutin of chlorine Xi Ting, 20-60% of 20-60% and the Plantagoside of 20-60%.
In the present invention further embodiment, described pharmaceutical composition is made up of chlorine Xi Ting, troxerutin and Plantagoside, and the percentage by weight between three is chlorine Xi Ting, the troxerutin of 45% and the Plantagoside of 30% of 25%; Also can be the chlorine Xi Ting of 20%, the troxerutin of 40% and the Plantagoside of 40%.
Another object of the present invention is to provide the application of described pharmaceutical composition in preparation treatment apoplexy and the sequela medicine that causes thereof.
The depression that preferably caused by apoplexy of described sequela further.
Advantage of the present invention:
The present invention is by a large amount of active and clinical trial, based on existing medicine, by screening and active checking, show that one has better synergistic pharmaceutical composition, said composition not only has the effect of preferably treatment apoplexy, and has better synergism treating in the depression caused by apoplexy.In addition, the present invention also it may be noted that when treating PSD, treated by psychotherapy while using pharmaceutical composition of the present invention, can produce best therapeutic effect to treatment PSD.
Detailed description of the invention
Further will describe the present invention in detail below.It is pointed out that following explanation is only illustrating the technical scheme that application claims is protected, any restriction not to these technical schemes.The content that protection scope of the present invention is recorded with appended claims is as the criterion.
Embodiment 1 pharmaceutical composition is to the protective effect of focal cerebral ischemia in rats
Get male SPragne-Dawley rat, body weight 300-350g; SD rat is fixing with lying on the back after chloral hydrate (40mg/kg) intraperitoneal anesthesia, right carotid (CCA is exposed through cervical region, common carotid artery), external carotid artery (ECA, extemal carotid artery) and internal carotid artery (x with, internal carotid artery).With the CCA ligation of silk thread by distal end, and it is for subsequent use to wear a silk thread at the nearly crotch of CCA, is first closed by CCA and ICA folder with micro-arterial clamp.An osculum is cut at the nearly furcation of ECA, the single stranded nylon line (diameter 0.34mm) of the smooth ball of one paragraph header end is inserted from otch, line is fastened in soft propelling, open the bulldog clamp on ICA, bolt line is made to enter into middle cerebral artery (MCA) initiating terminal along ICA, with silk thread gim peg line for subsequent use.From CCA with crotch to the point that meets obstructions (brain medium-sized artery section start) about 19-20mm.Whole ischemic period lighting lamp control Rat-rectum temperature is at 37.0-37.5 DEG C.After ischemia, ECA opening part return by the light pulling plug line of 90min, and the capable Reperfu-sion of the bulldog clamp opening more than CCA.Rats in sham-operated group does not insert except ICA except bolt line, and all the other operation processs are the same.After Reperfu-sion 22.5h, broken end gets brain, cuts into slices to Mus brain with interval 2mm, adopts TTC Determination Staining respectively to organize brain infarction area (infarction part is white, and normal segments is red).
Grouping and administering mode: be divided into sham operated rats, model group and administration group, administration group starts gastric infusion in one week in the preoperative, once a day, each administration group dosage is 3mg/kg, sham operated rats is identical with administration group with model group administering mode, but does not give medicine, is only the normal saline of equivalent.The compound by weight percentage composition of each administration group is as follows:
| ％ | Chlorine Xi Ting | Troxerutin | Plantagoside |
| Administration group 1 | 100 | - | - |
| Administration group 2 | - | 100 | - |
| Administration group 3 | - | - | 100 |
| Administration group 4 | 35 | 65 | - |
| Administration group 5 | 15 | 30 | 55 |
| Administration group 6 | 25 | 45 | 30 |
| Administration group 7 | 20 | 40 | 40 |
| Administration group 8 | 35 | 55 | 10 |
Each group through TTC dyeing after, brain infarction area percentage ratio is as follows:
| Infarct size (%) | |
| Sham operated rats | 0 |
| Model group | 39.7±5.8 |
| Administration group 1 | 37.8±4.9 |
| Administration group 2 | 31.4±6.2 |
| Administration group 3 | 38.5±5.1 |
| Administration group 4 | 25.4±5.7 |
| Administration group 5 | 21.9±4.6 |
| Administration group 6 | 14.6±4.3 |
| Administration group 7 | 17.5±4.4 |
| Administration group 8 | 23.1±5.3 |
Embodiment 2 pharmaceutical composition is to the pharmacodynamics test of focal cerebral ischemia depression model rat
The method adopting embodiment 1 to describe prepares Focal Ischemia-Reperfusion in Rats model, and after modeling success the 2nd day starts, and every day appoints the time of getting to be limited in by rat in special observation cage between 10:00-16:00, gives 2h behavior restriction, continuous 7 days.Sham operated rats is not carried out intraluminal middle cerebral artery occlusion in rats obstruction but is carried out behavior restriction, gastric infusion is started while behavior restriction, each administration group dosage is 1mg/kg, and the compound composition of each administration group is with embodiment 1, and sham operated rats and model group give normal saline.Behavior restriction and administration, after 7 days, carry out behavioristics's mensuration to rat, and measure Hou Qu rat cerebral tissue and measure monoamine neurotransmitters, concrete outcome is as follows:
1) behavioristics measures
| Horizontal movement score | Move both vertically score | Cleaning action number of times | |
| Sham operated rats | 96.3±8.2 | 36.9±4.3 | 3.9±0.8 |
| Model group | 23.6±6.7 | 12.1±3.2 | 0.7±0.6 |
| Administration group 1 | 48.9±7.4 | 19.8±3.7 | 2.1±0.9 |
| Administration group 2 | 32.9±6.5 | 11.6±3.9 | 0.7±0.5 |
| Administration group 3 | 29.8±5.4 | 13.7±3.4 | 0.9±0.6 |
| Administration group 4 | 61.3±6.9 | 25.1±4.4 | 2.6±0.7 |
| Administration group 5 | 73.7±7.8 | 27.2±3.3 | 2.9±0.8 |
| Administration group 6 | 88.1±8.2 | 35.4±4.8 | 4.1±1.1 |
| Administration group 7 | 82.6±7.5 | 31.3±4.1 | 3.7±0.9 |
| Administration group 8 | 71.6±7.1 | 25.3±3.9 | 2.8±0.7 |
2) monoamine neurotransmitters
| μg/g | Norepinephrine | Dopamine | Five hydroxytryptamine |
| Sham operated rats | 0.79±0.21 | 2.3±0.6 | 0.83±0.13 |
| Model group | 0.31±0.09 | 0.8±0.4 | 0.28±0.07 |
| Administration group 1 | 0.45±0.14 | 1.1±0.5 | 0.35±0.09 |
| Administration group 2 | 0.32±0.12 | 0.9±0.4 | 0.26±0.08 |
| Administration group 3 | 0.29±0.07 | 0.8±0.5 | 0.29±0.09 |
| Administration group 4 | 0.57±0.15 | 1.4±0.4 | 0.47±0.11 |
| Administration group 5 | 0.61±0.13 | 1.7±0.6 | 0.53±0.12 |
| Administration group 6 | 0.69±0.17 | 2.1±0.5 | 0.69±0.16 |
| Administration group 7 | 0.66±0.13 | 1.9±0.6 | 0.63±0.13 |
| Administration group 8 | 0.59±0.16 | 1.6±0.4 | 0.55±0.09 |
In each group of result data of embodiment 1 and 2, analyze through one-way ANOVA and find, administration group 6 and 7 is less than 0.01 relative to the p value of model group and other administration groups, illustrates that pharmaceutical composition of the present invention has best synergistic action effect under the composition and ratio of administration group 6 and 7.
Content of the present invention merely illustrates some claimed specific embodiments; one of them or more described technical characteristic can be combined with arbitrary one or more technical scheme in technical scheme; these technical schemes obtained through combination also in the application's protection domain, just as these technical schemes obtained through combination in the disclosure of invention concrete record.
Claims (9)
1. a pharmaceutical composition, it is made up of chlorine Xi Ting and troxerutin, and wherein the percentage by weight of the two is the troxerutin of chlorine Xi Ting and 1-99% of 1-99%.
2. pharmaceutical composition according to claim 1, is characterized in that, in described pharmaceutical composition, the percentage by weight of chlorine Xi Ting and troxerutin can be the troxerutin of chlorine Xi Ting and 20-80% of 20-80%.
3. pharmaceutical composition according to claim 2, is characterized in that, in described pharmaceutical composition, the percentage by weight of chlorine Xi Ting and troxerutin can be the troxerutin of chlorine Xi Ting and 55-75% of 25-45%.
4. pharmaceutical composition according to claim 1, it is characterized in that, can also comprise Plantagoside in described pharmaceutical composition, the percentage by weight of described chlorine Xi Ting, troxerutin and Plantagoside is the troxerutin of chlorine Xi Ting, 1-98% and the Plantagoside of 1-98% of 1-98%.
5. pharmaceutical composition according to claim 4, is characterized in that, in described pharmaceutical composition, the percentage by weight of chlorine Xi Ting, troxerutin and Plantagoside can be the troxerutin of chlorine Xi Ting, 20-60% and the Plantagoside of 20-60% of 20-60%.
6. pharmaceutical composition according to claim 5, is characterized in that, described pharmaceutical composition is made up of chlorine Xi Ting, troxerutin and Plantagoside, and the percentage by weight between three is chlorine Xi Ting, the troxerutin of 45% and the Plantagoside of 30% of 25%.
7. pharmaceutical composition according to claim 5, is characterized in that, described pharmaceutical composition is made up of chlorine Xi Ting, troxerutin and Plantagoside, and the percentage by weight between three is chlorine Xi Ting, the troxerutin of 40% and the Plantagoside of 40% of 20%.
8. the application of pharmaceutical composition described in any one of claim 1-7 in treatment apoplexy and the sequela medicine that causes thereof.
9. application according to claim 8, is characterized in that, the depression that described sequela is preferably caused by apoplexy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410798222.2A CN104434943A (en) | 2014-12-21 | 2014-12-21 | Pharmaceutical composition for treating cerebral stroke and cerebral stroke caused depression |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410798222.2A CN104434943A (en) | 2014-12-21 | 2014-12-21 | Pharmaceutical composition for treating cerebral stroke and cerebral stroke caused depression |
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| Publication Number | Publication Date |
|---|---|
| CN104434943A true CN104434943A (en) | 2015-03-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201410798222.2A Pending CN104434943A (en) | 2014-12-21 | 2014-12-21 | Pharmaceutical composition for treating cerebral stroke and cerebral stroke caused depression |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1524521A (en) * | 2003-09-16 | 2004-09-01 | 彬 崔 | Troxerutin for injection and method for preparing the same |
| CN101966194A (en) * | 2009-07-28 | 2011-02-09 | 成都中医药大学 | New application of scutellarin and derivatives thereof |
-
2014
- 2014-12-21 CN CN201410798222.2A patent/CN104434943A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1524521A (en) * | 2003-09-16 | 2004-09-01 | 彬 崔 | Troxerutin for injection and method for preparing the same |
| CN101966194A (en) * | 2009-07-28 | 2011-02-09 | 成都中医药大学 | New application of scutellarin and derivatives thereof |
Non-Patent Citations (6)
| Title |
|---|
| 孙伟等: "益气温阳活血法治疗脑卒中后抑郁34 例临床观察", 《福建中医药》 * |
| 孙建田: "氟西汀治疗急性首发脑卒中后抑郁的临床对照研究", 《安徽医学》 * |
| 张志民等: "卒中后抑郁对急性脑梗死预后的影响", 《四川医学》 * |
| 翟鲁辉等: "长春西汀治疗急性脑梗死的临床研究", 《实用神经疾病杂志》 * |
| 陈树新等: "173例脑梗死住院患者用药分析", 《药物流行病学杂志》 * |
| 马海英等: "氟西汀治疗脑梗塞伴抑郁症30例", 《中国药业》 * |
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Application publication date: 20150325 |
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