CN106668026A - Application of rosolic acid to preparation of anti-hypoxic medicine - Google Patents
Application of rosolic acid to preparation of anti-hypoxic medicine Download PDFInfo
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- CN106668026A CN106668026A CN201710097007.3A CN201710097007A CN106668026A CN 106668026 A CN106668026 A CN 106668026A CN 201710097007 A CN201710097007 A CN 201710097007A CN 106668026 A CN106668026 A CN 106668026A
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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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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Abstract
The invention relates to application of rosolic acid to preparation of an anti-hypoxic medicine, and belongs to the technical field of medicine preparation. The prepared medicine has good clinic application prospects, and the prepared anti-hypoxic medicine can realize the treatment on hypoxic diseases.
Description
Technical field
The present invention relates to field of medicine preparing technology, more particularly to a kind of euscaphic acid Jacaric acid answering in anti-anoxic medicine is prepared
With.
Background technology
Cell is the 26S Proteasome Structure and Function unit of human body.Organization of human body it is aging, first appear as aging and the cell of cell
The reduction of quantity.When Leukopenia is to certain amount, decline will organ dysfunction, or even threat to life.The people of 21 century
Body care goal, seeks to protect cell, improves cellular metabolism, strengthens the resistances against diseases of cell.Because oxygen is not enough in air
Physiology, the causes for pathological of (high altitude anoxia) or human body itself and enough oxygen can not be taken in, or cell can not make full use of oxygen
(subhealth state anoxia), can cause body metabolism, physiological function or modal change, and this state is exactly anoxia
(anoxia).Often there is dyspnea, skin and mucosa cyanosis, psychological problem in acute or severe depletion of oxygen, in addition loss of consciousness or
Stupor：Chronic hypoxia often shows the symptoms such as weak, headache, dizziness, pale complexion, inappetence；When human body cell oxygen content it is low
When the 65% of normal value, hypoxic cell even easily canceration causes cancer.
At present clinic is used for anti-hypoxia more than human-body sub-health anoxia using various Chinese medicine compound health product.Generally have
Radix Rhodiolae, Cordyceps, Semen Ginkgo, Fructus Hippophae, Radix Codonopsis, the Radix Astragali, Poria, Radix Ginseng, Herba Dracocephali tangutici, Radix Et Caulis Acanthopanacis Senticosi, Ganoderma, Fructus Lycii etc.
The compound preparation of Chinese medicine and its effective ingredient.For the anti-anoxic medicine that high altitude anoxia is commonly used is included based on Radix Rhodiolae extract
Compound preparation；FUFANG DANSHEN PIAN or FUFANG DANSHEN DIWAN；21 JIWEITA；By dexamethasone, aminophylline and it is stable made by change
Learn recurrence due to taking drug square preparation plateau health etc..Acetazolamide is the anti-high altitude anoxia medicine of the single component of FDA approvals.In in said medicine
Recurrence due to taking drug side generally works slow, and Time of Administration is long, it is adaptable to the health care conditioning of subhealth state, but for high altitude anoxia especially acute height
Former anoxia functions are undesirable.And the use of chemical synthetic drug often brings other side effect while anti-hypoxia.
The content of the invention
It is an object of the invention to provide a kind of application of euscaphic acid Jacaric acid in anti-anoxic medicine is prepared.Medicine prepared by the present invention
Thing has good potential applicability in clinical practice, and the anti-anoxic medicine for preparing can realize the treatment of anoxia class disease.
The invention provides a kind of application of euscaphic acid Jacaric acid in anti-hypoxia disease medicament is prepared.
Preferably, the anti-hypoxia disease includes uncomfortable in chest, shortness of breath, angina pectoriss caused by myocardial ischemia；Caused by cerebral anoxia
Dizziness, headache；High altitude anoxia cerebral edema, high altitude anoxia pulmonary edema.
Preferably, the dosage form of the medicine includes tablet, capsule, syrup and granule.
Preferably, the medicine also includes adjuvant, and the adjuvant includes starch, Lactose, sucrose, methylcellulose, hard
Fatty acid magnesium, micropowder silica gel, ethanol, citric acid, sodium benzoate, essence and pigment..
Preferably, the dosage of the medicine is 0.8~2.4mg/kg.
The invention provides a kind of application of euscaphic acid Jacaric acid in anti-anoxic medicine is prepared.Medicine prepared by the present invention can pass through
Antioxidant ability of organism is improved, improves Cellular respiration function, its anti-hypoxia effective dose is little, and in cell and whole animal not
It was observed that obvious toxic action, can be used to alleviating and treat body caused by anoxia and do not accommodate pathological changes, be particularly suited for plateau
Altitude sickness and visceral organ injury caused by anoxia.With good potential applicability in clinical practice, the anti-anoxic medicine for preparing can
Realize the treatment of anoxia class disease.Result of the test shows that it is big that medicine prepared by the present invention can significantly mitigate acute hypoxia
Mus cerebral edema, Human Umbilical Vein Endothelial Cells and Myocytes Anoxia are damaged and also have significant protective effect.
Specific embodiment
The invention provides a kind of application of euscaphic acid Jacaric acid in anti-hypoxia disease medicament is prepared.
The present invention originating without special restriction to the euscaphic acid Jacaric acid, using euscaphic acid Jacaric acid well known to those skilled in the art
Commercially available prod, such as purchased from the euscaphic acid Jacaric acid of Wuhu Dai Erta Pharmaceutical Technology Co., Ltd.In the present invention, the rose
The purity of common vetch acid is preferred>98%.
In the present invention, the anti-hypoxia disease includes uncomfortable in chest, shortness of breath, angina pectoriss caused by myocardial ischemia；Cerebral anoxia institute
The dizziness of cause, headache；High altitude anoxia cerebral edema, high altitude anoxia pulmonary edema.
In the present invention, the dosage form of the medicine includes tablet, capsule, syrup and granule.The present invention is to described dose
The preparation method of type medicine does not have special restriction, using the customary preparation methods of corresponding dosage form well known to those skilled in the art
.
In the present invention, the medicine also include adjuvant, the adjuvant include starch, Lactose, sucrose, methylcellulose,
One or more in magnesium stearate, micropowder silica gel, ethanol, citric acid, sodium benzoate, essence and pigment.The present invention is to described
The addition of adjuvant does not have special restriction, is added using the conventional addition of each adjuvant well known to those skilled in the art
.The present invention originating without special restriction to the adjuvant, using above-mentioned adjuvant well known to those skilled in the art
Commercially available prod.
In the present invention, the dosage of the medicine is 0.8~2.4mg/kg.
Do with reference to application of the specific embodiment to a kind of euscaphic acid Jacaric acid of present invention offer in anti-anoxic medicine is prepared
Further details of introduction, technical scheme includes but is not limited to following examples.
Embodiment 1
Tablet made by with euscaphic acid Jacaric acid as raw material
Above-mentioned formula is carried out into direct compression using tablet machine, tablet is obtained.
Embodiment 2
Capsule made by with euscaphic acid Jacaric acid as raw material
Euscaphic acid Jacaric acid 20mg
Starch 70mg
Said components are mixed, loads No. 2 capsules.
Embodiment 3
Oral syrup agent made by with euscaphic acid Jacaric acid as raw material：
Said components are added to the water and are adjusted to aequum, bottled after mixing.
Embodiment 4
Granule made by with euscaphic acid Jacaric acid as raw material：
Add in granulation machine after said components are mixed, make and packed after granule.
Embodiment 5
The anti-high altitude anoxia myocardial injury of euscaphic acid Jacaric acid
1st, method
(1) experiment packet：50 wister rats are randomly divided into into normal oxygen matched group, acute high altitude hypoxia model group, sun
Property medicine Dexamethasone group, euscaphic acid Jacaric acid high dose group and euscaphic acid Jacaric acid low dose group, per group of 10 rats.Raise at 20 ± 2 DEG C, freely
Drinking-water.Every time respectively gavage gives euscaphic acid Jacaric acid 15mg/kg and 5mg/kg for high dose group and low dose group rat, per minor tick 12h,
It is administered 3 times altogether；Then each gavage gives dexamethasone 6mg/kg, administration number of times and same euscaphic acid Jacaric acid interval time to positive drug group rat
Group；Often oxygen matched group and acute high altitude hypoxia model group rats give equal-volume physiology salt with same interval time and number of times gavage
Water.
(2) high altitude anoxia model is set up：In addition to normal oxygen matched group, each group rat is immediately placed on Low Pressure Oxygen after last gavage
Anoxia experiment is carried out in cabin, makes oxygen cabin reach the atmospheric pressure of height above sea level 7000m height, 15 ± 2 DEG C of temperature, humidity in 15min
30% ± 5%, anoxia 18h.Anoxia makes pressure in low-pressure oxygen cabin be down to height above sea level 150m atmospheric pressure in 15min after terminating
(the regional height above sea level of experiment).Often oxygen control rats are then normally raised in identical epidemic disaster out of my cabin.
(3) Indexs measure：
1. biochemical indicator detection：Each group rat goes out the rapid urethane of lumbar injection 25% anesthesia behind cabin, opens thoracic cavity, wins
Heart, prepares ventricular homogenate and detects that LDH, SOD activity and MDA, GSH contain in ventricular homogenate according to test kit explanation
Amount.
2. H.E dyeing：By the Cardiac muscle sections for preparing with dimethylbenzene dewax, and Jing step by step ethanol solution enters water.With
Afterwards 5min is contaminated with haematoxylin, tap water is rinsed, acidic alcohol differentiation 30s, tap water immersion 15min subsequently insert Yihong liquid
Middle 2min, conventional dehydration, transparent, mounting.Just putting basis of microscopic observation each group rat heart muscle changes in histopathology.
3. Nagar-Olsen dyeing：The Cardiac muscle sections for preparing are dewaxed with dimethylbenzene, and Jing ethanol solution step by step
Enter water.Subsequently 30s is contaminated with haematoxylin, distilled water flushing, acidic alcohol differentiation 15s, tap water rinses 5min, and dip-dye is put
0.1% basic fuchsin liquid 3min, distilled water flushing 10s, is subsequently dipped to pure acetone 8min, and 0.1% picric acid pure acetone solution enters
The rapid differentiation of row, conventional dehydration, transparent, mounting.
2 results
Compared with normal oxygen matched group, acute hypoxia model group cardiac muscular tissue LDH activity significantly improves (P<0.01),
MDA contents significantly rise (P<0.05), GSH contents significantly reduce (P<0.01), SOD activity significantly reduces (P<0.05).Flos Rosae Multiflorae
Sour high-concentration and low-concentration group and Dexamethasone group LDH activity and MDA contents are significantly reduced compared with acute hypoxia model group,
SOD activity and GSH contents are significantly increased (P compared with acute hypoxia model group<0.01 or P<0.05).Compare with normal oxygen
Group is compared, acute hypoxia model group.Euscaphic acid Jacaric acid high-concentration and low-concentration group and Dexamethasone group MDA content and acute hypoxia mould
Type group is compared and significantly reduces (P<0.01 or P<0.05) (table 1).
The euscaphic acid Jacaric acid of table 1 is to acute hypoxia rat heart muscle tissue SOD, the impact (x ± s, n=10) of MDA, GSH
Note:**P<The normal oxygen matched groups of 0.01vs；#P<0.05,##P<0.01vs anoxia model groups
Embodiment 6
Protective effect of the euscaphic acid Jacaric acid to EA.hy926 endotheliocyte anoxia-induced apoptosis is studied
1st, method
(1) EA.hy926 endotheliocytes hypoxia model sets up height sugar of the EA.hy926 endotheliocytes containing 10%FBS
DMEM culture fluid (culture fluid contains 100U/ml penicillins and 100 μ g/ml streptomycins) is cultivated in CO2 gas incubator, will
The EA.hy926 cells for growing into monolayer change the DMEM culture medium of serum-free sugar-free continuously after culture 12 hours, with advance with 95%
N2- 5%CO2The D-hanks liquid of gaseous mixture saturation 30min substitutes normal incubation medium, then culture plate is moved into into mixed gas culture
Case (95%N2, 5%CO2、O2Concentration ＜ 1%), in 37 DEG C of anoxia culture 2h.Experiment sets blank control group, anoxia model group, rose
Common vetch acid high concentration group (1 × 10-11Mol/L), concentration group (1 × 10 in euscaphic acid Jacaric acid-12Mol/L) and euscaphic acid Jacaric acid low concentration group (1 ×
10-13Mol/L), verapamil matched group (1 × 10-11Mol/L), totally 6 groups, per group of 8 holes.In addition to blank control group, other each groups
Equal anoxic treatment 2h, Normal group is then in 37 DEG C, 5%CO22h is synchronously incubated in incubator.
(2) mtt assay detection anoxia-induced apoptosis endotheliocyte metabolic activity takes out each group sample, and 20 μ lMTT (5g/ are added per hole
L), 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.Add 150 μ l DMSO to shake 15min, make crystallization
Fully dissolving, in determining at wavelength 570nm, reference wavelength 630nm, determines each hole absorbance (OD) value.
(3) biochemical indicator detection is inoculated in the EA.hy926 endotheliocytes of 24 orifice plates, hypoxia model group and euscaphic acid Jacaric acid
Intervention group anoxic treatment 2h, Normal group CO2 gas incubator is synchronously incubated, and takes the μ l of each group cell culture supernatant 200,
By test kit explanation LDH activity in colorimetric method for determining culture medium, intracellular MDA contents, SOD, CAT activity and GSH contents.
2nd, result
Compared with Normal group, hypoxia model group endotheliocyte viability is substantially reduced, and MDA contents substantially increase,
GSH contents and SOD, CAT activity are decreased obviously, and LDH leakages increase (P<0.01)；Compared with model group, in each concentration euscaphic acid Jacaric acid
Chrotoplast metabolic activity, SOD, CAT activity and GSH contents are improved, and MDA is produced and LDH leakages are reduced.(table 2-4) (P<
0.01)。
The euscaphic acid Jacaric acid of table 3 is to anoxia-induced apoptosis EA.hy926 cellular metabolism vigor and impact (x ± s, the n=of extracellular LDH activity
8)
**P<0.01vs matched groups；#P<0.05,##P<0.01vs model group
The impact (x ± s, n=8) of the euscaphic acid Jacaric acid of table 4 SOD activity intracellular to anoxia-induced apoptosis EA.hy926 and MDA contents
Note:**P<0.01vs matched groups；#P<0.05,##P<0.01vs model group
The impact (x ± s, n=8) of the euscaphic acid Jacaric acid of table 5 CAT activity intracellular to anoxia-induced apoptosis EA.hy926 and GSH contents
Note:**P<0.01vs matched groups；#P<0.05,##P<0.01vs model group
1 year animal experimental observation of Jing, using medicine of the present invention obvious toxic and side effects are not found to animal.
More than can be seen that, euscaphic acid Jacaric acid has significant anti-hypoxia damaging action, zoopery in addition confirms the drug toxicity
It is relatively low, can be used for preparing the medicine for preventing and treating anoxia-induced apoptosis.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (5)
1. application of a kind of euscaphic acid Jacaric acid in anti-hypoxia disease medicament is prepared.
2. application according to claim 1, it is characterised in that the anti-hypoxia disease includes breast caused by myocardial ischemia
Vexed, shortness of breath, angina pectoriss；Dizziness, headache caused by cerebral anoxia；High altitude anoxia cerebral edema, high altitude anoxia pulmonary edema.
3. application according to claim 1, it is characterised in that the dosage form of the medicine include tablet, capsule, syrup and
Granule.
4. application according to claim 1, it is characterised in that the medicine also include adjuvant, the adjuvant include starch,
Lactose, sucrose, methylcellulose, magnesium stearate, micropowder silica gel, ethanol, citric acid, sodium benzoate, essence and pigment.
5. application according to claim 1, it is characterised in that the dosage of the medicine is 0.8~2.4mg/kg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710097007.3A CN106668026A (en) | 2017-02-22 | 2017-02-22 | Application of rosolic acid to preparation of anti-hypoxic medicine |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710097007.3A CN106668026A (en) | 2017-02-22 | 2017-02-22 | Application of rosolic acid to preparation of anti-hypoxic medicine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112816296A (en) * | 2020-12-30 | 2021-05-18 | 苏州堪赛尔医学检验有限公司 | Hematoxylin-alkaline re-redden-picric acid staining kit and staining method thereof |
-
2017
- 2017-02-22 CN CN201710097007.3A patent/CN106668026A/en active Pending
Non-Patent Citations (5)
| Title |
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| PARK, HEE-JUHN等: "Inhibitory effect of euscaphic acid and tormentic acid from the roots of Rosa rugosa on high fat diet-induced obesity in the rat", 《SAENGYAK HAKHOECHI》 * |
| 王舒: "蕨麻正丁醇层化学成分及抗缺氧活性研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
| 王舒等: "蕨麻正丁醇部位对缺氧损伤心肌细胞的保护作用", 《天津中医药》 * |
| 王鲁君等: "蕨麻正丁醇部位对急性低压缺氧小鼠的保护作用", 《武警医学院学报》 * |
| 龚海英等: "蕨麻正丁醇部位对EAHY926内皮细胞缺氧损伤的保护作用", 《武警后勤学院学报（医学版）》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112816296A (en) * | 2020-12-30 | 2021-05-18 | 苏州堪赛尔医学检验有限公司 | Hematoxylin-alkaline re-redden-picric acid staining kit and staining method thereof |
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Application publication date: 20170517 |