CN107865875B - A pharmaceutical composition containing aescin A - Google Patents
A pharmaceutical composition containing aescin A Download PDFInfo
- Publication number
- CN107865875B CN107865875B CN201711065750.7A CN201711065750A CN107865875B CN 107865875 B CN107865875 B CN 107865875B CN 201711065750 A CN201711065750 A CN 201711065750A CN 107865875 B CN107865875 B CN 107865875B
- Authority
- CN
- China
- Prior art keywords
- aescin
- nicotinic acid
- reduce
- sodium salt
- injection
- 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.)
- Active
Links
Images
Classifications
-
- 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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- 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 discloses a pharmaceutical composition for treating ischemic stroke, which consists of aescin A or sodium salt thereof and nicotinic acid, wherein the weight ratio of the aescin A or the sodium salt thereof to the nicotinic acid is 2-20: 0.5-5. The composition provided by the invention can reduce the neurological impairment degree and mortality of an animal model with cerebral ischemia reperfusion injury, reduce the infarct volume and brain water content caused by cerebral ischemia, obviously improve the activity of SOD in rat brain tissues, reduce the generation of MDA, protect cell membranes from being damaged by free radicals, improve the activity of LDH in ischemic brain tissues and reduce the accumulation of lactic acid, and is an ideal medicament for treating ischemic stroke.
Description
Technical Field
The invention belongs to the field of pharmacy, and particularly relates to a pharmaceutical composition for treating ischemic stroke, which is composed of aescin A or sodium salt thereof and nicotinic acid.
Background
Aescin, also called aescin acid, is triterpene saponin extracted from seeds of plant of Aesculus of Aesculaceae, and has molecular formula of C55H86O24. Aescin or its sodium salt has antiinflammatory and antiedemic effects, and can be used for treating cerebral edema, wound, etc.
The aescin contains many kinds of saponin compounds and is named as aescin A, aescin B, aescin C and aescin D before and after liquid phase peak. They are isomers of each other (see figure 1), and the escin currently used clinically is a mixture of escin A, B, C, D and other components.
Pharmacological research shows that, in the components of the aescin, the aescin A has the strongest pharmacological activity and the best clinical curative effect on cerebral edema. In addition, the high-purity aescin A can solve the problems that the quality of the current aescin product is unstable, the safety is difficult to guarantee, and the like. Therefore, the development of the aescine A has great clinical significance.
Nicotinic acid is also known as pyridine-3-formic acid, nicotinic acid and vitamin B3, and has a molecular formula: c6H5NO2It is one of 13 vitamins essential to human body, is a water-soluble vitamin, and belongs to vitamin B group. Nicotinic acid has strong function of dilating blood vessels, and is clinically used for treating headache, migraine, tinnitus, cerebral artery thrombosis, inner ear vertigo and the like.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition consisting of aescin A or sodium salt thereof and nicotinic acid, which can be used for treating cerebral arterial thrombosis and has obvious synergistic effect.
A pharmaceutical composition for treating ischemic stroke comprises aescin A or sodium salt thereof and nicotinic acid, wherein the weight ratio of the aescin A or the sodium salt thereof to the nicotinic acid is 2-20: 0.5-5.
In a preferred embodiment of the invention, the weight ratio of the aescin A or the sodium salt thereof to the nicotinic acid is 5-10: 1-3.
Further preferably, the weight ratio of the aescin A or the sodium salt thereof to the nicotinic acid is 7: 2.
The result of the pharmacodynamic experiment shows that: the pharmaceutical composition provided by the invention can reduce the neurological impairment degree and mortality of an animal model with cerebral ischemia reperfusion injury, reduce the infarct volume and brain water content caused by cerebral ischemia, obviously improve the activity of SOD in rat brain tissues, reduce the generation of MDA, protect cell membranes from being damaged by free radicals, simultaneously improve the activity of LDH in ischemic brain tissues and reduce the accumulation of lactic acid. Pathological tissue section results also show that the composition can relieve nerve cell edema and vacuole dragging phenomena caused by ischemia, and the composition can relieve the damage degree of the nerve cell membrane of a cerebral ischemia reperfusion rat and protect the integrity of the nerve cell membrane. The test results show that the medicine provided by the invention is an ideal medicine for treating ischemic stroke.
The composition provided by the invention can be administered orally or by injection, preferably intravenous injection, preferably in the form of powder injection or injection, and the injection amount of the composition relative to an adult is 1-30 mg/day (calculated by aescin A), preferably 5-10 mg/day.
The powder injection or the injection can be prepared into products with different specifications according to clinical needs, and the specification of the invention is preferably 5mg or 10mg for each.
Drawings
FIG. 1 is the structural formula of aescin A, B, C, D.
Detailed Description
The present invention will be described in detail below with reference to examples.
Test drugs:
composition injection: mixing aescin A and nicotinic acid in the weight ratio of 10: 1. 7: 2. 5: 3, dissolving in water for injection to prepare injection containing 5mg of aescin A per ml.
Aescin A injection: dissolving aescin A in water for injection to obtain injection containing aescin A5 mg/ml.
And (3) nicotinic acid injection: dissolving nicotinic acid in water for injection to obtain injection containing nicotinic acid 5 mg/ml.
1. Establishing a rat cerebral ischemia reperfusion injury model: male SD rats weighing 230-250 g are anesthetized by intraperitoneal injection of 25% urethane solution, fixed on an operating table in a lateral decubitus position, and subjected to incision in the middle of the neck, the common carotid artery is exposed, the internal carotid artery is separated, the common carotid artery and the internal carotid artery are clamped, a nylon wire is slowly pushed towards the human cranium direction of the internal carotid artery through the main incision of the external carotid artery, and reaches the thinner anterior cerebral artery, so that the middle cerebral artery is blocked, the local cerebral blood flow is fully blocked, the wound is sutured, the local cerebral blood flow condition is monitored by a transcranial Doppler blood flow analyzer, and the local cerebral blood flow condition is used as a main index for judging the success of a cerebral ischemia model.
2. The administration scheme is as follows: the rats after molding are randomly divided into a model group, an aescin A group, a nicotinic acid group, a low-dosage group, a medium-dosage group and a high-dosage group, and each group contains 20 rats. Respectively injecting 1.0ml/kg of solvent injection into tail vein 1min before cerebral ischemia; 1.0mg/kg of aescin A injection; ③ 1.0mg/kg of nicotinic acid injection; (iv) 1.0mg/kg of composition injection (aescin A: 10: 1); fifthly, 1.0mg/kg of composition injection (aescin A: nicotinic acid: 7: 2) and 1.0mg/kg of composition injection (aescin A: nicotinic acid: 5: 3).
3. Grading and scoring the behavioral defects of the rats: after administration, the general condition and the degree of neurological deficit of the rats in each group were closely observed within 24h of reperfusion in an ischemia model, and the behavioral deficit of the rats was scored according to literature reports: (1) lifting the tail about 1 foot away from the ground, observing the situations of forelimbs, and scoring 4 points for those with forelimb adductors, or scoring 0 point; (2) rats were placed on a smooth floor and examined for resistance to pushing. According to different resistance degrees, the evaluation is 1-3 points; (3) the forelimbs of the rats were placed on a metal mesh and their muscle tone was observed. And (4) evaluating the degree of the muscle tension reduction as 0-3 points, and combining the points, wherein the higher the point is, the more serious the behavior disorder of the animal is. The results are shown in Table 1.
TABLE 1 Effect of each group of drugs on neurological deficit and mortality in cerebral ischemia models (n 20)
Note: in comparison with the set of models,*P<0.05，**P<0.01。
4. and (3) observing the volume of cerebral ischemic infarction: after 24h of reperfusion after administration, each group of rats were sacrificed, the wet weight of the brain was taken from the whole brain, sliced, stained in 2% triphenyltetrazolium chloride (TFC) solution for 30min, fixed, and the pale (infarct) zone and the non-pale (normal) zone were separated, and the infarct range was defined as the percentage of the infarct zone range weight to the brain weight. And (4) placing the dyed brain tissue in an oven to dry to constant weight, weighing the dry weight, and calculating the water content of the brain. Brain water content (brain tissue wet weight-brain tissue dry weight)/brain tissue wet weight × 100%.
Table 2 influence of each group of drugs on cerebral infarction volume and water content in cerebral ischemia model (n ═ 20)
| Group of | Cerebral infarction dead volume (%) | Water content (%) |
| Model set | 25.1±1.7 | 74.9±4.8 |
| Aescin group A | 20.7±1.7 | 63.7±4.7* |
| Nicotinic acid group | 23.3±1.7 | 73.5±4.7 |
| Composition Low dose group (10: 1) | 18.4±1.5* | 49.8±4.4** |
| Composition Medium dose group (7: 2) | 14.1±1.5** | 44.2±4.4** |
| Composition high dose group (5: 3) | 15.7±1.5** | 58.2±4.5* |
Note: in comparison with the set of models,*P<0.05，**P<0.01。
5. and (3) determination of biochemical indexes: after 24h of reperfusion after dosing, each group of rats was sacrificed, brains were rapidly weighed and made into a 10% brain tissue homogenate with physiological saline. Centrifuging at low temperature, collecting supernatant, and determining contents of superoxide dismutase (SOD), Malondialdehyde (MDA) and Lactate Dehydrogenase (LDH) in brain tissue by the method above the kit instruction.
TABLE 3 Effect of each group of drugs on SOD, LDH and MDA content in cerebral ischemia model (n ═ 20)
Note: in comparison with the set of models,*P<0.05，**P<0.01。
6. pathological histological examination: after 24h of reperfusion after dosing, each group of rats was sacrificed, whole brains were removed and fixed in 10% formaldehyde solution, paraffin embedded, pathological sections were made, HE stained, and histopathological examination was performed on each group of sections with an optical microscope. The result shows that the normal group of rats has complete cerebral tissue cortex structure, normal nerve cell morphology and complete structure. The model group rat ischemia brain tissue cortex area cell arrangement is scattered, the phenomena of tissue edema and cell vacuole are serious, and the phenomenon that glial cells phagocytose degeneration neurons is obvious. Compared with the model group, the low, medium and high dose groups of the composition have obviously reduced pathological changes, and tissues have no obvious pathological changes such as necrosis, inflammatory cell infiltration and the like.
7. And (4) conclusion: the pharmaceutical composition provided by the invention can reduce the neurological impairment degree and mortality of an animal model with cerebral ischemia reperfusion injury, reduce the infarct volume and brain water content caused by cerebral ischemia, obviously improve the activity of SOD in rat brain tissues, reduce the generation of MDA, protect cell membranes from being damaged by free radicals, simultaneously improve the activity of LDH in ischemic brain tissues and reduce the accumulation of lactic acid. Pathological tissue section results also show that the composition can relieve nerve cell edema and vacuole dragging phenomena caused by ischemia, and the composition can relieve the damage degree of the nerve cell membrane of a cerebral ischemia reperfusion rat and protect the integrity of the nerve cell membrane. The test results show that the medicine provided by the invention is an ideal medicine for treating ischemic stroke. Tests also show that the aescin A or the sodium salt thereof and the nicotinic acid have obvious synergistic effect after being combined, and the treatment effect of the aescin A or the sodium salt thereof or the nicotinic acid on the cerebral ischemic stroke is obviously better than that of the single use of the aescin A or the sodium salt thereof or the nicotinic acid.
Claims (3)
1. An application of a pharmaceutical composition containing aescin A in preparing a medicine for treating cerebral arterial thrombosis is characterized in that: the pharmaceutical composition consists of aescin A or sodium salt thereof and nicotinic acid, wherein the weight ratio of the aescin A or sodium salt thereof to the nicotinic acid is 5-10: 1-3.
2. The use of claim 1, wherein: the weight ratio of the aescin A or the sodium salt thereof to the nicotinic acid is 7: 2.
3. The use of claim 1, wherein: the medicine is powder injection or injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711065750.7A CN107865875B (en) | 2017-11-02 | 2017-11-02 | A pharmaceutical composition containing aescin A |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711065750.7A CN107865875B (en) | 2017-11-02 | 2017-11-02 | A pharmaceutical composition containing aescin A |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107865875A CN107865875A (en) | 2018-04-03 |
| CN107865875B true CN107865875B (en) | 2020-10-30 |
Family
ID=61752876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711065750.7A Active CN107865875B (en) | 2017-11-02 | 2017-11-02 | A pharmaceutical composition containing aescin A |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107865875B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110585222B (en) * | 2019-10-12 | 2023-05-09 | 西南医科大学 | Application of aescin compound in preparation of medicines |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104788440B (en) * | 2015-04-03 | 2017-12-26 | 苏州大学 | Nicotinic acid derivates and its application |
-
2017
- 2017-11-02 CN CN201711065750.7A patent/CN107865875B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107865875A (en) | 2018-04-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ribeiro et al. | Natural lipids-based NLC containing lidocaine: from pre-formulation to in vivo studies | |
| US10561670B2 (en) | Compositions comprising acidic extracts of mastic gum | |
| CN105663027A (en) | External preparation containing sirolimus as well as preparation method and application thereof | |
| CN105434337B (en) | Propranolol Hydrochloride Submicron Emulsion gel and its preparation method and application | |
| JP2021505650A (en) | Ophthalmic drug preparations and their use | |
| CN107865875B (en) | A pharmaceutical composition containing aescin A | |
| Zhou et al. | Gold nanoclusters for optimizing the general efficacies of herbal medicines on nerve repair after spinal cord injury | |
| CN108042552B (en) | A pharmaceutical composition comprising aescin B or its sodium salt and nicotinic acid | |
| CN108042553B (en) | Pharmaceutical composition for treating cerebral arterial thrombosis | |
| CN102526065A (en) | Compound injection preparation for treating cardiovascular and cerebrovascular diseases and preparation method thereof | |
| Su et al. | Novel multifunctional bionanoparticles modified with sialic acid for stroke treatment | |
| CN109481396A (en) | A kind of fullerene water solution, injection and preparation method thereof | |
| CN101947247B (en) | Method for preparing ginkgodipyidamolum injection | |
| Zhang et al. | Non-invasive drug delivery systems mediated by nanocarriers and molecular dynamics simulation for posterior eye disease therapeutics: Virtual screening, construction and comparison | |
| CN100431562C (en) | Chinese traditional medicinal preparation containing red sange root and safflower for treating cardiovascular and cerebrovascular diseases and preparing process thereof | |
| CN102988461A (en) | Rhodiola rosea injection and preparation method thereof | |
| CN109078191A (en) | O- hydroxyethyl chitosan/tanshinone IIA nanometer formulation treatment ischemic cerebrovascular disease purposes | |
| CN103690496B (en) | Freeze-drying medicine composition containing sodium ozagrel | |
| CN111317745B (en) | Application of water-soluble fullerene structure in preparation of medicine for treating Parkinson's disease | |
| CN109481464A (en) | A kind of injection fullerene emulsion and preparation method thereof | |
| CN102526583B (en) | Chinese medicinal composition for treating senile dementia and preparation method and application thereof | |
| Bagde et al. | Polyherbal Nanogel: A Potential Remedy For The Management Of Rheumatoid Arthritis | |
| CN107260827B (en) | Compound essential oil for treating retained afterbirth of dairy cow and preparation method thereof | |
| JP2002173434A (en) | Antiallergic composition | |
| CN116421513A (en) | Skin care product composition with sensitive muscle Shu Gong repairing effect and preparation method thereof |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |