CN107865842A - Applications of the Isovitexin in anti-anoxic medicine is prepared - Google Patents
Applications of the Isovitexin in anti-anoxic medicine is prepared Download PDFInfo
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- CN107865842A CN107865842A CN201610843375.3A CN201610843375A CN107865842A CN 107865842 A CN107865842 A CN 107865842A CN 201610843375 A CN201610843375 A CN 201610843375A CN 107865842 A CN107865842 A CN 107865842A
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- isovitexin
- anoxic
- anoxia
- anoxic medicine
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses applications of the Isovitexin in anti-anoxic medicine is prepared.The present invention passes through entirety and cellular level anoxia model; observe Isovitexin oxygen lack resistant function; as a result show that Isovitexin is remarkably improved survival rate and the time-to-live of asphyxia anoxia and acute decompression hypoxia mouse; mitigate the myocardial damage of drug specificity hypoxia mice; neonatal rat myocardial cell and nerve cell anoxia-induced apoptosis in vitro culture also have significant protective effect, there is provided purposes of the Isovitexin in anti-anoxic medicine is prepared.
Description
Technical field
The present invention relates to compound Isovitexin new application, more particularly to Isovitexin to prepare anti-anoxic medicine
In application.
Background technology
The essential condition that oxygen is the mankind and many biologies are depended on for existence.Hypoxemia (Hypoxia) refers to body vital movement institute
The oxygen needed can not obtain the supply of abundance.Oxygen and hypoxemia are the most important key factors of vital movement, are that life science is managed substantially
The important topic of opinion.The formation of hypoxemia can be divided into three classes：The first kind is the reduction of external environment oxygen content, makes normal physiological activity mistake
Cheng Buneng absorbs enough oxygen, such as plateau and aviation anoxic；Second class refers to because disease etc. causes extraneous normal oxygen amount can not be abundant
Reach in body, cause the anoxic of the heart, brain and respiratory system etc.；3rd class is zmount of oxygen consumption needed for body activities, has exceeded life
The ability of mobilization is managed, relative oxygen supply deficiency is caused, is common in strenuous exercise and the amount of transfiniting work.Long-term hypoxemia is that harmful to human is good for
The important hidden danger of health, severe patient can threat to life.Therefore, hypoxemia causes the heart, brain and respiratory system equivalent damage to turn into 21 century
One of medical field subject matter anxious to be resolved.
Compound Isovitexin of the present invention be one deliver within 2013 (Ebenezer de Mello Cruz,
et al.,Leishmanicidal activity of Cecropia pachystachya flavonoids:Arginase
inhibition and altered mitochondrial DNA arrangement.Phytochemistry,89(2013)
71-77.) noval chemical compound, the compound possess brand-new framework types, and current purposes merely relates to anti-hepatitis virus
(Ebenezer de Mello Cruz, et al., Leishmanicidal activity of Cecropia
pachystachya flavonoids:Arginase inhibition and altered mitochondrial DNA
Arrangement.Phytochemistry, 89 (2013) 71-77.), it is anti-in preparation for Isovitexin of the present invention
Purposes in anoxic medicine belongs to first public, and due to belonging to brand-new structure type, and it is obtained for Substituted phenyl-lactic acid is strong
It is unexpected, in the absence of the possibility that any enlightenment is provided by other compounds, possess prominent substantive distinguishing features, while for resisting
Anoxic obviously has significant progressive.
The content of the invention
For above-mentioned prior art, it is an object of the invention to be found that there is Isovitexin significant anti anoxia to make
With available for preventing and treating anoxia-induced apoptosis disease, so as to add Isovitexin application field.
Applications of the Isovitexin of the present invention in anti-anoxic medicine is prepared, it is that Isovitexin is preparing preventing and treating anoxic
Application in property damage medicine.Shown in the compound Isovitexin structures such as formula (I)：
Applications of the Isovitexin in anti-anoxic medicine, Isovitexin can improve asphyxia anoxia and acute subtract
Press survival rate and the time-to-live of hypoxia mice.
A kind of anti-anoxic medicine, it is that active component addition auxiliary material is prepared by Isovitexin, preparation method is to take 5 grams
Compound Isovitexin, 195 grams of dextrin is added, mixed, conventional tablet presses are made 1000.
A kind of anti-anoxic medicine, it is that active component addition auxiliary material is prepared by Isovitexin, preparation method is to take 5 grams
Compound Isovitexin, 195 grams of starch is added, mixed, it is encapsulated to be made 1000.
Purposes of the Isovitexin of the present invention in anti-anoxic medicine is prepared belongs to first public, due to skeleton class
Type belongs to brand-new framework types, and its Substituted phenyl-lactic acid is unexpectedly strong, any in the absence of being provided by other compounds
The possibility of enlightenment, possess prominent substantive distinguishing features, while obviously there is significant progress for anti anoxia.
Embodiment
Compound Isovitexin involved in the present invention preparation method is referring to document (Ebenezer de Mello
Cruz, et al., Leishmanicidal activity of Cecropia pachystachya flavonoids:
Arginase inhibition and altered mitochondrial DNA arrangement.Phytochemistry,
89(2013)71–77.)
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by specific reality
Any restrictions of example are applied, but are defined in the claims.
Embodiment 1：The preparation of compound Isovitexin tablets involved in the present invention：
5 g of compound Isovitexin are taken, add 195 grams of dextrin, are mixed, conventional tablet presses are made 1000.
Embodiment 2：The preparation of compound Isovitexin capsules involved in the present invention：
5 g of compound Isovitexin are taken, add 195 grams of starch, are mixed, it is encapsulated to be made 1000.
Its pharmaceutical activity is further illustrated below by pharmacodynamic experiment.
Experimental example 1：Test mouse specificity myocardial anoxia experiment
1st, method：75 kunming mices, Nanjing Medical University's Experimental Animal Center, body weight (20 ± 2) g.It is randomly divided into 5
Group, gastric infusion.First 2 groups are given 0.3% sodium carboxymethylcellulose (CMC-Na) solution, and latter 3 groups are given respectively
Isovitexin0.015、0.03g·Kg-1, Propranolol Hydrochloride 0.03gKg-1, after 50min, in addition to the 1st group, equal abdominal cavity note
Penetrate isoprel (ISO) 15mgKg-1, after 15min, mouse is put into normobaric hypoxia device, when recording dead mouse
Between and oxygen demand.
2nd, result：
Isoprel can increase myocardial oxygen consumption by excited heart beta receptor.This experiment is shown, with solvent pair
Compared according to group, Isovitexin 0.015,0.03gKg-1Myocardial oxygen consumption caused by isoprel (ISO) can significantly be resisted
Amount increase (P<, while the time-to-live (P that extends under anoxia in mice air-tight state 0.01)<0.01) it, the results are shown in Table 1.
The Isovitexin of table 1 causes the influence (x ± s, n=15) of specific hypoxia mice to isoprel
Compared with control group, * P<0.01, compared with isoprel group, #P<0.01
Test the experiment of two mouse normal pressure asphyxia anoxias
1st, method：
60 kunming mices, Nanjing Medical University's Experimental Animal Center, body weight (20 ± 2) g.4 groups are randomly divided into, gavage is given
Medicine.1st group is given 0.3% carboxylic first
Base sodium cellulosate (CMC-Na) solution, the 2nd group is given Propranolol Hydrochloride 0.03gKg-1, pro groups.3rd, 4 group
The CMC-Na solution containing Isovitexin is given respectively, and concentration is respectively 0.015,0.03gKg-1.After 50min is administered, it is placed in
In wide-mouth bottle and cover tightly bottle stopper (bottle in place 5g soda limes).Stop, for mark, recording the mouse survival time with breathing.
2nd, result：
Compared with vehicle control group, Isovitexin 0.015,0.03gKg-1Make mouse under the conditions of atmospheric closed
Time-to-live extends 28.12% and 40.14% respectively, and difference has conspicuousness (P<0.01, P<0.05).
Test the experiment of three mouse hypobaric hypoxias
1st, method：
40 kunming mices, Nanjing Medical University's Experimental Animal Center, body weight (20 ± 2) g.4 groups are randomly divided into, gavage is given
Medicine.Administration group gives Isovitexin, and concentration is respectively 0.015,0.03gKg-1, control group gives 0.3%CMC-Na solution,
Gavage volume is 2mlKg-1.After 50min, administration group and control group respectively take 5, are put into decompressor, in 26.7Kpa
Stop decompression when (equivalent to height above sea level about 10000m), keep this pressure constant, when animal dead 50%, stop decompression immediately,
Air is slowly put into, animal, the death of record each group and viable count is taken out, repeats to experiment and complete.
2nd, result：
Isovitexin 0.015、0.030g·Kg-1Make survival rate of the mouse under the conditions of hypobaric hypoxia by control group
30%th, 20% improve to 70%, 80%, difference has conspicuousness (P<0.05).
The protective effect of four pairs of Myocytes Anoxia damages of experiment
1st, method：
(1) Neonatal Rat Primary Cardiomyocytes culture：Newborn 1-3d SD suckling mouses take ventricular muscles to be cut into about 1mm3Size tissue block,
0.25% trypsase -0.02%EDTA is added, with being digested at 37 DEG C.In addition to digestion supernatant discards first, collect on each time
Clear liquid stops digestion, and cardiac muscle cell's precipitation is collected by centrifugation, adds DMEM/F-12 culture mediums and Brdu containing 10% hyclone
(final concentration 0.1mmol/L), gently piping and druming mix, cell suspension are made, is inoculated in blake bottle, in 37 DEG C, 5%CO2Culture
70min is incubated in case, makes most non-myocardial infarctions adherent.
Draw bottle inner cell suspension to count, adjustment cell concentration is 1 × 105Individual/ml, 24 orifice plates are inoculated into, per hole 1ml；
96 orifice plates, per hole 200ul.After 48h cell attachments, the DMEM/F-12 culture mediums (being free of Brdu) containing 10% hyclone are changed,
Change liquid 1 time within every 2 days later.
(2) Myocytes Anoxia model is established：Culture 4d cardiac muscle cell is taken, changes serum-free DMEM/F-12 culture mediums company
After continuous culture 12h, (95%N is pre-charged with sugar-free D-Hanks liquid2- 5%CO2Gaseous mixture saturation 30min) substitute normal culture
Base, then culture plate is moved into rapidly and is connected with 95%N2- 5%CO2In the hypoxia device of gaseous mixture, exhaust outlet is detected with oxygen analyser
Oxygen concentration (<1%), 37 DEG C of anoxic culture 6h.
(3) experiment packet：Experiment sets blank control group, anoxia model group, anoxic+Isovitexin A group (concentration
0.024mg/ml), B groups (concentration 0.012mg/ml), C groups (concentration 0.006mg/ml), totally 5 groups, every group of 6 holes.Except blank control
Group is outer, and the equal anoxic treatment 6h of other each groups, Normal group is then in 37 DEG C, 5%CO26h is synchronously incubated in incubator.
(4) anoxia-induced apoptosis cardiac muscle cell MTT experiment：Each group sample is taken out, 20ul MTT (5g/L) are added per hole, in 37
DEG C, 5%CO2Continue to be incubated 4h in incubator, terminate culture, a kind of rhyme scheme in Chinese operas serving as the prelude to a complete score for voices.150ul DMSO shaking 15min are added, make crystallization fully molten
Solution, at measure wavelength 570nm, reference wavelength 630nm, determine each hole absorbance (OD) value.
MTT metabolic rates (%)=experimental group OD values/Normal group OD value × 100%
(5) biochemical indicator detects：The each group cell culture supernatant for being incubated at 24 orifice plates is taken, with colorimetric method for determining LDH, CK
Activity, intracellular SOD activity is determined with xanthine oxidase；With the intracellular MDA contents of thiobarbituricacidα- colorimetric method for determining,
Specific detection process and operating method are carried out by kit specification.
2nd, result：
Cardiac muscle cells because anoxic sustain damage when, mitochondrial function is abnormal, and oxidation-respiration chain is damaged, electron transmission resistance
Disconnected, ATP produces reduction.Succinate dehydrogenase is one of complex enzyme important in respiratory chain of succinic acid oxidation, can be catalyzed butanedioic acid
Dehydrogenation generates fumaric acid, so that FAD receives two hydrogen atom generation FADH2, hydrogen is then passed into C againOQ, generation
COQH2, continue the electron transfer process of respiratory chain.So the activity of succinate dehydrogenase, can be damaged with reflecting myocardium cell hypoxia
The degree of wound.MTT experiment principle, it is insoluble exactly can be catalyzed Thiazolyl blue (MTT) generation aubergine using succinate dehydrogenase
The characteristic of color products, the cytoactive of each group is reflected by the measure of absorbance.This experimental result is shown：Concentration is respectively
0.024mg/ml, 0.012mg/ml, 0.006mg/ml Isovitexin, MTT measure OD values and are significantly higher than model group, show
Cytoactive (P can be dramatically increased<0.01), illustrate that Isovitexin can be to anti anoxia to cardiac muscle cell's succinate dehydrogenase activity
Infringement, maintain Hypoxic cell respiratory function；When anoxic causes cell membrane damage, intracellular LDH, CK will leak outside, and lead
LDH, CK activity rise in culture medium are caused, this experiment shows 3 dosage groups, and LDH, CK are active in culture medium compared with model group
It is obvious to reduce, show that Isovitexin under Conditions of Acute Hypoxia in Human Body, can keep the integrality of myocardial cell membrane, the above results are shown in Table
2。
SOD reflects the ability of cell clearance free radical, and MDA reflects Cell membrane lipids Peroxidative damage degree, this examination
3 dosage groups tested intracellular SOD activity rise compared with model group, MDA is horizontal to produce decline, is shown in Table 3, shows
Isovitexin can remove the ability of free radical to cell membrane oxidative damage caused by anti anoxia by strengthening cardiac muscle cell.
Influences (x ± s, n=6) of the Isovitexin of table 2 to leakage quantity outside anoxic myocardial LDH, CK
Compared with model group, * * P<0.01, * P<0.05
Influences (x ± s, n=8) of the Isovitexin of table 3 to anoxic myocardial vigor, SOD activity and MDA contents
Compared with model group, * * P<0.01, * P<0.05
Conclusion：When Isovitexin is remarkably improved survival rate and the survival of asphyxia anoxia and acute decompression hypoxia mouse
Between, mitigate the myocardial damage of drug specificity hypoxia mice, neonatal rat myocardial cell and nerve cell anoxic in vitro culture damage
Wound also has significant protective effect, there is provided purposes of the Isovitexin in anti-anoxic medicine is prepared.
Claims (4)
- Applications of the 1.Isovitexin in anti-anoxic medicine, shown in the compound Isovitexin structures such as formula (I)：
- 2. applications of the Isovitexin as claimed in claim 1 in anti-anoxic medicine, it is characterised in that Isovitexin can be carried The survival rate of high asphyxia anoxia and acute decompression hypoxia mouse and time-to-live.
- 3. a kind of anti-anoxic medicine, it is characterised in that the Isovitexin as described in claim 1 is that active component adds auxiliary material system Standby to form, preparation method adds 195 grams of dextrin, mixed, conventional tablet presses are made 1000 to take 5 g of compound Isovitexin Piece.
- 4. a kind of anti-anoxic medicine, it is characterised in that the Isovitexin as described in claim 1 is that active component adds auxiliary material system Standby to form, preparation method adds 195 grams of starch, mixing is encapsulated to be made 1000 to take 5 g of compound Isovitexin.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610843375.3A CN107865842A (en) | 2016-09-23 | 2016-09-23 | Applications of the Isovitexin in anti-anoxic medicine is prepared |
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| CN201610843375.3A CN107865842A (en) | 2016-09-23 | 2016-09-23 | Applications of the Isovitexin in anti-anoxic medicine is prepared |
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| CN107865842A true CN107865842A (en) | 2018-04-03 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112870190A (en) * | 2021-01-19 | 2021-06-01 | 中国人民解放军空军军医大学 | Application of isovitexin in preparation of medicine for treating nerve injury caused by ischemia and/or hypoxia |
-
2016
- 2016-09-23 CN CN201610843375.3A patent/CN107865842A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112870190A (en) * | 2021-01-19 | 2021-06-01 | 中国人民解放军空军军医大学 | Application of isovitexin in preparation of medicine for treating nerve injury caused by ischemia and/or hypoxia |
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Application publication date: 20180403 |