CN106474099A - The application in preventing and treating altitude sickness of salvianolic acid A and its derivant - Google Patents
The application in preventing and treating altitude sickness of salvianolic acid A and its derivant Download PDFInfo
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- CN106474099A CN106474099A CN201611019862.4A CN201611019862A CN106474099A CN 106474099 A CN106474099 A CN 106474099A CN 201611019862 A CN201611019862 A CN 201611019862A CN 106474099 A CN106474099 A CN 106474099A
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- Prior art keywords
- salvianolic acid
- derivant
- treatment
- prevention
- altitude sickness
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Classifications
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- A—HUMAN NECESSITIES
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Abstract
The present invention relates to field of medicaments is and in particular to salvianolic acid A and its derivant are in the application preventing and/or treating altitude sickness.Salvianolic acid A cardiovascular diseasess, protection cerebrovascular endothelial cell, protection ischemic tissue of brain damage, prevent and/or treat cerebral thrombosiss, improve cerebral ischemia after function of nervous system's symptom, prevention and/or treatment diabetes and complication, suppression brain neuron damage or death, prevention and/or treatment cerebral thrombosiss, save cerebral ischemic penumbra medicine, treatment multi-drug resistance of the tumor, prevention and treatment acquired immune deficiency syndrome (AIDS) encephalopathy in terms of etc. aspect application, have no salvianolic acid A and its derivant prevention and/or treatment altitude sickness report.
Description
Technical field
The present invention relates to a kind of salvianolic acid A and its derivant, in the application preventing and/or treating altitude sickness, belong to medical skill
Art field.
Background technology
Altitude sickness refers to enter the area (including high mountain and plateau) in more than 3000m for the height above sea level in people's short time, is counting
Hour or a couple of days in, occur the vexed swollen, appetite of obstinate headache, dizziness, tired, irritated, insomnia, cardiopalmus, shortness of breath, chest to subtract
Move back, the disease of the symptom such as nausea and vomiting, abdominal distention diarrhoea, dim eyesight, tinnitus, epistaxis, brothers are numb or both hands are twitched.Its symptom weight
Vary with each individual, severe one may occur in which the matters of aggravation such as plateau pneumochysiss, cerebral edema, heart failure, these diseases are as cannot get in time
Process, death will be led to, the lighter is typically gradually disappeared through 1 week about symptom, but also have and continue relatively long or delay into High Altitude
Disease.
The risk factor of altitude sickness is a lot, such as the harsh climate environment such as low pressure, cold, but topmost reason is people
Body anoxia, makes energy-producing materials in body can not effectively aoxidize and releases energy, and so that the photodynamic species ATP of the activity of sustaining life is produced
Reduce, lead to Na+/K+/ATP pumping function obstacle, so that cell physiological function occurs obstacle, thus producing various accordingly facing
The former disease symptoms of the height of bed.
The treatment meanss of altitude sickness are that (1) gives high flow capacity oxygen uptake or mask oxygen inhalation treatment at present；(2) withdraw High aititude ground
Area, transfers low altitude area to；(3) Drug therapy.First two method effectively, but is limited by certain condition.Drug treatment
Mainly there are diuretic acetazolamide, vasodilator nimodipine and hormone medicine such as dexamethasone.Wherein acetazolamide is
It is conventional, but easily cause that urine volume is many and the ill effect such as dehydration.Some are also had to be Chinese traditional compound medicine, mainly favourable capsules " Weishukang " for curing
Deng, but onset is slow, and it is low to take absorption efficiency.So, develop a kind of Small side effects, determined curative effect, take simplicity and become high
The Main way of former disease protective agents, becomes China's development of the West Regions and the urgent needss of western national defense construction and national security.
Recent study finds, in Radix Salviae Miltiorrhizae, the activity of the anti-myocardial ischemina of salvianolic acid constituents is than danshensu and former youngster
Tea aldehyde is strong, and wherein salvianolic acid A is one of anti-oxidizing compounds the strongest of being currently known, and salvianolic acid A is in antioxidation, myocardial ischemia
Protection, antithrombotic, neuroprotective, anti-hepatic fibrosis, prevent and treat the many aspects such as diabetes and complication there is extensive pharmacology and live
Property.(Zhang Li, Zhang Weiku, Zhao Ying, Yang Xiuying, square Flos Nelumbinis, Wang Shoubao, Du Guanhua. (2011). the research of salvianolic acid A and progress.
CHINA JOURNAL OF CHINESE MATERIA MEDICA (19), 2603-2609.) existing a large amount of with regard to salvianolic acid A extracting method, preparation method, detection method special
Profit (application number CN201210487322.4, CN200710001055.4, CN200610165779.8, CN200610048130.8,
CN200710099618.8、CN201210557058.7、CN201010143656.0、CN200910169900.8、
CN201010143714.X、CN201210488782.9、CN200610012615.1、CN201110141512.6、
CN200710000542.9、CN201110083924.9、CN201210487598.2、CN201010148488.4、
CN201210487600.6、CN201210487643.4、CN201010541651.3、CN201010620911.6、
CN201210487597.8, CN201310487751.6) red phenol is prepared by methods such as extraction, conversion, column chromatography, extractions
Sour A, purity reaches more than 90%, and so that the quality of salvianolic acid A raw material is ensured, patent (application number
CN200610170267.0、CN201210489085.5、CN201210489575.5、CN201210490336.1、
CN201210489121.8、CN200710130325.1、CN201210488066.0、CN201210488078.3、
CN201210488905.9, CN201310705521.2, CN201410068605.4) report salvianolic acid A in cardiovascular diseasess, guarantor
Shield cerebrovascular endothelial cell, protection ischemic tissue of brain are damaged, are prevented and/or treat cerebral thrombosiss, improve the neural work(after cerebral ischemia
Energy symptom, prevention and/or treatment diabetes and complication, suppression brain neuron damage or death, prevention and/or treatment brain
Thrombosis, save cerebral ischemic penumbra medicine, treatment multi-drug resistance of the tumor, the prevention and treatment aspect such as acquired immune deficiency syndrome (AIDS) encephalopathy aspect should
With having no salvianolic acid A and its report of derivant prevention and/or treatment altitude sickness.
Content of the invention
In view of this, the present invention provides new application, the prevention for altitude sickness and the treatment of salvianolic acid A and its derivant.
Overcome the shortcomings of worry preventing and treating plateau medicine.
To achieve these goals, the present invention provides following technical scheme：
Using the compound of logical formula (I), the treatment for altitude sickness and/or prevention.
Further, described salvianolic acid A derivant preferred salvianolic acid A sodium salt, salvianolic acid A potassium salt, salvianolic acid A ammonium salt, pellet
Phenolic acid A methyl ester, salvianolic acid A ethyl ester, salvianolic acid A propyl ester, salvianolic acid A isopropyl ester, acetyl salvianolic acid A.
Further, described salvianolic acid A derivant preferred salvianolic acid A sodium salt, salvianolic acid A methyl ester, salvianolic acid A ethyl ester, second
Acyl salvianolic acid A.
Further, described salvianolic acid A derivant preferred salvianolic acid A ethyl ester.
In Formulas I salvianolic acid A and its derivant can using known method preparation, such as patent of invention CN200610145453,
CN200710099618.8,201210177567.7 etc..
The invention still further relates to using salvianolic acid A in Formulas I and its derivant as the pharmaceutical preparation of active component.This drug regimen
Thing can be prepared by method well known in the art.Can pass through the compounds of this invention and one or more pharmaceutically acceptable solid
Or Auxiliary Liquid Material, make the solid preparation being applied to human body or animal or liquid preparation.Salvianolic acid A and its spread out in formula I
Biological content in its pharmaceutical preparation is usually 1-95 weight %.
Salvianolic acid A and its derivant or can be administered in a unit containing its pharmaceutical preparation in the present invention, administration
Approach can be intestinal or non-bowel, as oral, intravenous injection, intramuscular injection, subcutaneous injection, nasal cavity, oral mucosa etc..
Salvianolic acid A of the present invention and its derivant make tablet, can widely use various excipient well known in the art, bag
Include diluent, adhesive, wetting agent, disintegrating agent, lubricant, fluidizer.Diluent can be starch, dextrin, sucrose, Fructus Vitis viniferae
Sugar, Lactose, Mannitol, Microcrystalline Cellulose, calcium sulfate etc.；Wetting agent can be water, ethanol etc.；Adhesive can be starch slurry,
Dextrin, Microcrystalline Cellulose, sodium carboxymethyl cellulose, methylcellulose, hydroxypropyl methyl cellulose, ethyl cellulose, polyethylene
Ketopyrrolidine, Polyethylene Glycol etc.；Disintegrating agent can be Microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, crosslinked polyethylene pyrroles
Alkanone, crosslinked hydroxyl sodium carboxymethyl cellulose, carboxymethyl starch sodium, sodium bicarbonate etc.；Lubricant and fluidizer can be Pulvis Talci,
Silicon dioxide etc..
Tablet can also be made further coated tablet, such as thin membrane coated tablet, ECT etc..
In order to administration unit is made capsule, salvianolic acid A and its derivant can be mixed with diluent, fluidizer,
Mixture is placed directly within hard capsule or soft capsule.Also the compounds of this invention can be made with diluent, adhesive, disintegrating agent
Granule or micropill, then be placed in hard capsule.For preparing each diluent of the compounds of this invention tablet, adhesive, wetting agent, collapsing
The adjuvants such as solution agent, fluidizer can also be used for preparing the capsule of the compounds of this invention.
It is that the compounds of this invention is made injection, solvent can be made and added with water, ethanol etc. or their mixture
Solubilizing agent commonly used in the art, cosolvent, pH adjusting agent, osmotic pressure regulator and antioxidant etc. in right amount.As vegetation freeze-dried powder
Agent, can also add Mannitol, glucose etc. as proppant.
Additionally, if desired, preservative, correctivess or other additives can also be added in pharmaceutical preparation.
In order to reach medication purpose, the medicine of the present invention or pharmaceutical preparation can be administered with any known medication.
, according to the property that will prevent or treat disease and the order of severity, patient's is individual for the dosage of the compounds of this invention
Body situation, route of administration and dosage form can have large-scale change.In general, the daily suitable dose of the compounds of this invention is
0.1-200mg/kg body weight, preferably 0.5-10mg/kg body weight, most preferably 1-4mg/kg body weight.Above-mentioned dosage can a dosage
Unit or be divided into several dosage unit administration, this clinical experience depending on doctor and the administration side with other treatment means
Case.
The compound of the present invention or preparation can individually be taken, or merge use with other treatment medicine or symptomatic drugs.When
When the compounds of this invention and other treatment have coordinative role, dosage should be adjusted according to practical situation.
The present invention simulates Rats at Plateau anoxia experimental evaluation salvianolic acid A by rat hypobaric hypoxia cabin and its derivant moral resists
Hypobaric hypoxia acts on, and result confirms that salvianolic acid A and its derivant have protective effect to animal under the conditions of hypobaric hypoxia.Result
As follows：
Experimental technique：
Take healthy male SD rat 120, adaptability is randomly divided into 12 groups by body weight after raising 3 days：Normal group, lack
Oxygen model group, sharp capsules " Weishukang " for curing group (100mg/kg), salvianolic acid A group (2mg/kg), salvianolic acid A sodium salt group (2mg/kg), red phenol
Sour A potassium salt group (2mg/kg), salvianolic acid A ammonium salt group (2mg/kg), salvianolic acid A methyl ester group (2mg/kg), salvianolic acid A ethyl ester group
(2mg/kg), salvianolic acid A propyl ester group (2mg/kg), salvianolic acid A isopropyl ester group (2mg/kg), acetyl salvianolic acid A group (2mg/kg),
Every group 10.Once, totally 3 times, administered volume is 10ml/kg to the daily gastric infusion of each group animal, (Normal group and anoxia mould
Type group gives isopyknic distilled water).60min after last dose, in addition to Normal group, each group rat is placed in hypobaric hypoxia cabin
In, airtight hatch door, with the decompression of 10m/s- speed, simulation rises to 7000 meters of height above sea level (8.2%O2,41.02kPa), temperature 18～
26 DEG C, adjust air inlet valve after maintaining 8h, normal height above sea level is slowly dropped to 20m/s speed.Open hatch door, rapid execution
Animal, takes lungs and brain, weighs moisture immediately, and then 60 DEG C of dryings 72 hours, after reaching constant weight, weigh dry weight again.By with
Lower formula calculates brain coefficient, brain water content, paragonimus cyst and moisture content of lung.Brain/paragonimus cyst=organ weights/body weight；Brain/lung is aqueous
Amount=(weight in wet base-dry weight)/weight in wet base × 100%.
Salvianolic acid A and its derivant are as shown in table 1 to simulation Rats at Plateau anoxia experimental result.
Table 1：The protective effect to simulated high altitude hypoxia rat model of salvianolic acid A and its derivant
Note：P*<0.05,P**<0.01, P compared with anoxia model group#<0.05,P##<0.01, compared with normal control
Shown by result above, salvianolic acid A group, salvianolic acid A sodium salt group, salvianolic acid A potassium salt group, salvianolic acid A ammonium salt group, pellet
Phenolic acid A ethyl ester group and acetyl salvianolic acid A group all can obviously improve cerebral edema and the pulmonary edema of hypoxia rat model, brain coefficient, brain
Water content, paragonimus cyst and moisture content of lung significantly reduce (P than model group<0.01 or P<0.05).Wherein, salvianolic acid A group, salvianolic acid
A sodium salt group, salvianolic acid A ethyl ester group and acetyl salvianolic acid A group effect are preferable；Salvianolic acid A propyl ester group can significantly improve Hypoxic Rats
Cerebral edema, brain coefficient and brain water content significantly reduce (P than model group<0.01 or P<0.05)；Salvianolic acid A isopropyl ester group can show
Write the pulmonary edema improving Hypoxic Rats, paragonimus cyst and moisture content of lung significantly reduce (P than model group<0.05).
Specific embodiments
Following is in conjunction with specific embodiments and experimental example, and the present invention is expanded on further.But these embodiments are limited to explanation originally
Invent rather than be used for limiting the scope of the present invention.
Embodiment 1
Salvianolic acid A powder pin：
Salvianolic acid A, Mannitol, sodium thiosulfate are added to 800ml water for injection by prescription, with using 0.5% hydroxide
Sodium adjusts pH to 4-6；Stirred with 0.1% injection activated carbon, 60 degree are incubated 30 minutes, and filtered while hot takes off charcoal, and filtrate fills
Penetrate with water to 1000ml, degerming fine straining, fill, in 200 10ml cillin bottles, is partly jumped a queue, send into freeze dryer, -40 spend pre-freeze 2h,
It is evacuated to 10Pa～20Pa, be incubated 3h, -10 DEG C of insulation 16h at -25 DEG C, 30 DEG C are dried 3h, tamponade outlet, prepared salvianolic acid A
Powder pin.
Embodiment 2
Salvianolic acid A ethyl ester tablet：
Salvianolic acid A ethyl ester is pulverized 80 mesh sieves, weighs the salvianolic acid A ethyl ester after sieving, spray-dried lactose, crosslinked poly-
Dimension ketone, sodium sulfite mix homogeneously, the micropowder silica gel adding 60 mesh sieves mixes, and is eventually adding magnesium stearate and mixes, 7mm
Circular scrobicula stamping.Stomach dissolution type coating pre-mixing agent is dissolved in purified water, makes the coating solution that solid content is 15%, using height
Effect seed-coating machine is coated, coating weight gain 3%, prepared salvianolic acid A ethyl ester coated tablet (in terms of salvianolic acid A, 60mg/ piece).
Embodiment 3
Salvianolic acid A sodium salt capsule：
Salvianolic acid A sodium salt, vitamin C are pulverized, crosses 80 mesh sieves, weigh the salvianolic acid A sodium salt after pulverizing and sieving, vitamin
C, Microcrystalline Cellulose, Pregelatinized Starch, are sufficiently mixed uniformly, add dehydrated alcohol to make soft material in right amount, 20 mesh sieves are pelletized, 40 DEG C
Under the conditions of be dried, dry particl arranges with 20 mesh sieves, and addition cross-linking sodium carboxymethyl cellulose, magnesium stearate mix homogeneously obtain always mixed medicine
Powder, by total mixed drug powder fill in 2# Capsuleses, grain weight 170mg, obtain final product salvianolic acid A sodium salt capsule (in terms of salvianolic acid A, 60mg/
Grain).
Embodiment 4
Acetyl salvianolic acid A drop pill：
Acetyl salvianolic acid A, vitamin C are pulverized, crosses 120 mesh sieves, weigh the polyethylene glycol 6000 of recipe quantity, heating in water bath
90 DEG C, stirring makes it all melt, and weighs the acetyl salvianolic acid A after pulverizing and sieving, vitamin C is added to polyethylene glycol 6000
In, stirring makes it fully dissolve.Medicinal liquid is placed in pill dripping machine, fluid temperature is maintained between 80～90 DEG C, by medicinal liquid with 30
Drip/speed of minute instills in condensing agent (, liquid paraffin, 3～10 DEG C), collect drop pill in discharging opening, wipe surface with gauze
Liquid paraffin, room temperature is dried naturally, obtains final product acetyl salvianolic acid A drop pill (in terms of salvianolic acid A, 10mg/ ball).
It should be understood that after the above-mentioned teachings having read the present invention, those skilled in the art can make to the present invention
Various changes or modification, these equivalent form of values equally fall within the application appended claims limited range.
Claims (7)
1. salvianolic acid A and its derivant preparation prevention and or treatment altitude sickness in application.
2. application according to claim 1 is it is characterised in that the derivant of salvianolic acid A is selected from salvianolic acid A sodium salt, red phenol
Sour A ammonium salt, salvianolic acid A potassium salt, salvianolic acid A methyl ester, salvianolic acid A ethyl ester, salvianolic acid A propyl ester, salvianolic acid A isopropyl ester and acetyl are red
Any one in phenolic acid A.
3. the application according to claim 1 or 2 is it is characterised in that the derivant of salvianolic acid A is selected from salvianolic acid A sodium salt and red phenol
Any one in sour A methyl ester, salvianolic acid A ethyl ester and acetyl salvianolic acid A.
4. the application according to claim 1,2 or 3 is it is characterised in that the derivant of salvianolic acid A is salvianolic acid A ethyl ester.
5. application according to claim 1, it is characterised in that salvianolic acid A and its derivant and the adjuvant medically commonly used, is made
Solid preparation or liquid preparation.
6. application according to claim 5 it is characterised in that described solid preparation be tablet, capsule, granule, soft
Capsule, drop pill and powder pin.
7. application according to claim 6 is it is characterised in that described liquid preparation is oral liquid and injection.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108309988A (en) * | 2018-05-04 | 2018-07-24 | 遵义医学院 | Erp57 inhibitor compounds and application |
| CN109820889A (en) * | 2019-02-26 | 2019-05-31 | 安徽工程大学 | Salvia root P.E is preparing protein-tyrosine phosphatase 1B inhibitor and prevention and/or is treating the application in diabetes B drug |
-
2016
- 2016-11-18 CN CN201611019862.4A patent/CN106474099A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108309988A (en) * | 2018-05-04 | 2018-07-24 | 遵义医学院 | Erp57 inhibitor compounds and application |
| CN108309988B (en) * | 2018-05-04 | 2020-05-26 | 遵义医学院 | ERp57 inhibitor compound and application |
| CN109820889A (en) * | 2019-02-26 | 2019-05-31 | 安徽工程大学 | Salvia root P.E is preparing protein-tyrosine phosphatase 1B inhibitor and prevention and/or is treating the application in diabetes B drug |
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Application publication date: 20170308 |