CN101033245A - Preparation method and application of pedunculoside - Google Patents
Preparation method and application of pedunculoside Download PDFInfo
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- CN101033245A CN101033245A CN 200610017186 CN200610017186A CN101033245A CN 101033245 A CN101033245 A CN 101033245A CN 200610017186 CN200610017186 CN 200610017186 CN 200610017186 A CN200610017186 A CN 200610017186A CN 101033245 A CN101033245 A CN 101033245A
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- peltatin glucoside
- peltatin
- glucoside
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- 238000002360 preparation method Methods 0.000 title claims description 30
- LARPFJIXBULVPK-OIWQCSEESA-N Pedunculoside Natural products O=C(O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]12[C@@H]([C@@](O)(C)[C@H](C)CC1)C=1[C@](C)([C@@]3(C)[C@@H]([C@@]4(C)[C@H]([C@@](CO)(C)[C@@H](O)CC4)CC3)CC=1)CC2 LARPFJIXBULVPK-OIWQCSEESA-N 0.000 title description 2
- LARPFJIXBULVPK-FBAXZNBGSA-N [(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (1r,2r,4as,6ar,6as,6br,8ar,9r,10s,12ar,14bs)-1,10-dihydroxy-9-(hydroxymethyl)-1,2,6a,6b,9,12a-hexamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylate Chemical compound O=C([C@]12CC[C@H]([C@@]([C@H]1C=1[C@@]([C@@]3(CC[C@H]4[C@](C)(CO)[C@@H](O)CC[C@]4(C)[C@H]3CC=1)C)(C)CC2)(C)O)C)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O LARPFJIXBULVPK-FBAXZNBGSA-N 0.000 title description 2
- LARPFJIXBULVPK-UHFFFAOYSA-N peduncloside Natural products C1CC(C2(CCC3C(C)(CO)C(O)CCC3(C)C2CC=2)C)(C)C=2C2C(O)(C)C(C)CCC21C(=O)OC1OC(CO)C(O)C(O)C1O LARPFJIXBULVPK-UHFFFAOYSA-N 0.000 title description 2
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
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- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
This invention relates to ilexin, drug combination of ilexin and its extraction method, which is used to treat CHD, angina pectoris, stroke, cardiac infarction and other cerebral vascular diseases. It uses ethanol for extraction, adds water into the extract, centrifuges to get the sediments and supernatant. Sediments are added 50-95% ethanol for extraction and filtration, the liquid is concentrated, placed and filtrated, and the sediments are dried to get a part of total saponin, the saponin is crystallized by ethanol to get a part of ilexin. The supernatant is enriched and centrifuged for the sediments, which is washed with appropriate water and crystallized by ethanol after dried to get another part of ilxin. Two parts of ilxin are put together and recrystallized for several times to get the pure ilxin, which content can be more than 98.0%.
Description
Technical field
The present invention relates to a kind of medicine for the treatment of diseases of cardiovascular and cerebrovascular systems and protective foods and preparation method thereof, specifically the composition and the corresponding preparation method thereof of the effective constituent Peltatin glucoside of Chinese medicine Ilex rotunda Thunb., the medicine that contains Peltatin glucoside and protective foods.
Background technology
Ilex rotunda Thunb. is the bark of holly plant Aquifoliaceae holly Ilex rotunda Thunb. Ilex rotunda Thunb., main product in Guangxi, Guangdong Province, have effects such as clearing heat and detoxicating, swelling and pain relieving.Be used for flu, tonsillitis, swelling and pain in the throat, acute gastroenteritis, treating rheumatic ostealgia; Wound is controlled in external application, carbuncle furuncle sore, traumatic hemorrhage, burn and scald.Chemical ingredients mainly contains triterpenoid saponin, flavonoid glycoside, phenols, tannin etc., and its saponin component content is higher, is about 7-8%.Wen Dongxu etc.
[1](herbal medicine, 1991,22 (6), 246-248) therefrom isolate saponin component Peltatin glucoside (Pedunculoside), molecular formula is: C
36H
58O
10Structural formula is:
In recent years, document
[2.3](Pharmacology and Clinics of Chinese Materia Medica, 1998; 14 (4), 22-24, Chinese medicinal materials, 1997; 20 (6), 303-305) report Ilex rotunda Thunb. alcohol extract has anti-arrhythmia and the effect of protection hypoxic-ischemic cardiac muscle.But because the Ilex rotunda Thunb. alcohol extract belongs to crude preparation by using, definite effective constituent it be unclear that.Pang Xiaoxiong etc.
[4](ACAD J GCP, 1997,13 (2), 103～104) extraction and the separation method of report Peltatin glucoside are to be ground into meal with getting Ilex rotunda Thunb., with 95% alcohol reflux three times, extracting solution is concentrated into small volume, the distilled water that adds equivalent, standing over night, centrifugal, throw out is washed with an amount of, dry crude product, crude product be with chloroform backflow weeding of grease soluble components, and residue is with 50% ethanol heat treated, the filtering insolubles, filtrate is placed, and filters, and the gained crystallization is through silica gel column chromatography, use chloroform: methyl alcohol: water (72: 1) lower floor wash-out, thin-layer chromatography checks, merge identical component after, get Peltatin glucoside with 50% ethyl alcohol recrystallization.
The deficiencies in the prior art are to need with the chloroform degreasing of severe toxicity and carry out silica gel column chromatography and separate, and output is little, and the cycle is long, the cost height, and complicated operation, processing condition can't adapt to the suitability for industrialized production needs.
Summary of the invention
The technical problem to be solved in the present invention is: the effective constituent Peltatin glucoside of diseases of cardiovascular and cerebrovascular systems such as development treatment irregular pulse, myocardial ischemia, cerebral ischemia, and the pharmaceutical composition of Peltatin glucoside.The present invention also comprises a kind of Peltatin glucoside preparation method of suitable mass industrialized production.
A kind of Peltatin glucoside for the treatment of diseases of cardiovascular and cerebrovascular systems, available following method preparation:
Get the Ilex rotunda Thunb. meal, use alcohol reflux, united extraction liquid is concentrated into the medicinal extract shape, adds water, and heating is stirred, and standing over night is centrifugal, gets throw out and supernatant liquor.Throw out adds the 50-95% alcohol reflux, filters, and filtrate is concentrated, places, and filters, and drying precipitate gets a part of total saponins, and total saponins adds 10-100 50-95% alcohol crystal doubly, gets a part of Peltatin glucoside.Supernatant concentration is put and is chilled to room temperature, and is centrifugal, and throw out is used the 50-95% alcohol crystal with an amount of washing, dry back, makes another part Peltatin glucoside again.The Peltatin glucoside that makes for twice merges, and the 50-95% ethanol of doubly measuring with 10-100 is recrystallization repeatedly, the pure product of Peltatin glucoside.
Described Peltatin glucoside, its preparation method is: get the Ilex rotunda Thunb. meal, with 2-10 50-95% alcohol reflux doubly three times, each 1-3 hour, united extraction liquid is concentrated into the medicinal extract shape, adds 3-10 water doubly, heating, stir, standing over night, centrifugal, get throw out and supernatant liquor.Throw out adds the 50-95% alcohol reflux, filters, and filtrate is concentrated, places, and filters, and drying precipitate gets a part of total saponins, and total saponins adds 10-100 50-95% alcohol crystal doubly, gets a part of Peltatin glucoside.Supernatant concentration is to 1/2-2 times of volume, put and be chilled to room temperature, centrifugal, throw out is given a baby a bath on the third day after its birth time with suitable quantity of water, drying, the 50-95% alcohol crystal of doubly measuring with 10-100, make another part Peltatin glucoside coarse-grain again, the Peltatin glucoside that makes for twice merges, and the 50-95% ethanol of doubly measuring with 10-100 is recrystallization repeatedly, the pure product of Peltatin glucoside.
Above-mentioned Peltatin glucoside preparation method is characterized in that: with 2-10 50-95% alcohol reflux doubly, extracting solution is concentrated into medicinal extract, adds water, and is centrifugal, gets throw out and supernatant liquor.Throw out adds the 50-95% alcohol reflux, filters, and filtrate is concentrated, places, and filters, and drying precipitate gets a part of total saponins, and total saponins adds 10-100 50-95% alcohol crystal doubly, gets a part of Peltatin glucoside.Supernatant concentration, centrifugal, get throw out, drying with the 50-95% alcohol crystal that 10-50 doubly measures, makes another part Peltatin glucoside coarse-grain again, the Peltatin glucoside that makes for twice merges, and the 50-95% ethanol of doubly measuring with 10-100 is recrystallization repeatedly, the pure product of Peltatin glucoside.Its content is greater than 98.0%.
The pharmaceutical composition that is used for the treatment of diseases of cardiovascular and cerebrovascular systems wherein contains aforementioned each the Peltatin glucoside and the pharmaceutically acceptable carrier of treatment significant quantity.
Described pharmaceutical composition is characterized in that: be made up of Peltatin glucoside and oral preparations auxiliary material and injection auxiliary material basically; Be pill, oral liquid, injection liquid, instillation, lyophilized powder, microcapsule, capsule, tablet or various slowly-releasing or quick-release tablet.
Aforementioned preparation of drug combination method, available following steps make:
Taking polyethylene glycol 6000 and/or Macrogol 4000 are in 90-100 ℃, and mixed melting adds Peltatin glucoside and mixes, and routine is made dripping pill.It is characterized in that: by weight, taking polyethylene glycol 6000 and/or Macrogol 4000 1-4 part behind 90-100 ℃ of mixed melting, add Peltatin glucoside raw material 1-2 part and mix, and routine is made dripping pill.
Aforementioned preparation of drug combination method, available following steps make:
Get Peltatin glucoside, add the 5-25% polyglycol solution, heating in water bath makes dissolving, puts coldly, with 5-25% polyoxyethylene glycol (400) solution dilution, is made into injection liquid.It is characterized in that: get Peltatin glucoside 160mg, add 5-25% polyglycol solution 500ml dilution, make dissolving, put coldly, filter, add 5-25% polyoxyethylene glycol (400) solution, be made into the 2000ml injection liquid with 80 ℃ of heating in water bath.
Essence for a better understanding of the present invention will illustrate its application in pharmacy field with the pharmacological testing and the result of Peltatin glucoside below.
One, chmice acute toxicity test
1. test method
With adapting to 20 mouse (male and female half and half) fasting of 3 days of nursing 12 hours, can't help water,
Tried thing and be made into the tolerant peak concentration of mouse with distilled water, once irritate stomach for mouse with the tolerant maximum volume of mouse (0.4ml/10g), observed continuously 14 days, the response situation of record animal is a maximum tolerated dose not produce dead maximal dose.Calculate total dosage, extrapolate the multiple that is equivalent to clinical consumption.
2. test-results
With the tolerant peak concentration of mouse (33%), irritated stomach in 2 times/1 day for mouse with the tolerant maximum volume of mouse (0.4ml/10g), observed continuously 14 days, none example is dead as a result.
It is 13.2g/kg that mouse is once irritated the maximum tolerated dose that stomach gives Peltatin glucoside.
Two, rat long term toxicity test
1. the method rat oral gavage gives Peltatin glucoside 300mg/kg, 150mg/kg, 75mg/kg, and be administered once every day, and administration is 6 days weekly, and in 13 weeks of successive administration, control group gives with volume solvent (20ml/kg).Each administration group rat hair color gloss, body weight gain are normal as a result.Hematology, serum biochemistry are learned and are checked that each dosage group of demonstration compares indifference with control group.
2. result
2.1 influence (table 1) to hematological indices
Rat orally give Peltatin glucoside, and each treated animal hematological indices (Hb, RBC, Ret, PT, TT, PLT) inspection all in normal range, is compared indifference with control group.
2.2 influence (table 2) to each biochemical indicator of serum
The serum biochemistry index of surveying (comprise AST, ALT, ALP, TP, ALB, BUN, TCHO, GLU, Crea, TBIL, TG, CK, NA, CL, K), each treated animal index all in normal range, compares indifference with control group.
The table 1-1 Peltatin glucoside administration phase is learned the influence (X ± SD) of index to rat blood
Each administration group and the relatively more equal indifference of blank group
Table 1-2 Peltatin glucoside decubation is learned the influence (X ± SD) of index to rat blood
Each administration group and the relatively more equal indifference of blank group
The table 2-1 Peltatin glucoside administration phase is to the biochemical influence of rat blood (X ± SD)
Compare * P＜0.05 with the blank group
Table 2-2 Peltatin glucoside decubation is to the biochemical influence of rat blood (X ± SD)
Each administration group and the relatively more equal indifference of blank group
Three, pharmacodynamic experiment
1. Peltatin glucoside is to ARR influence
1.1 method
Get 40 of the big white mouse of body weight 200 ± 20 gram, random packet, every group 10, male and female half and half are divided into dosage group (50mg/kg), Peltatin glucoside small dose group (25mg/kg), lignocaine group (5mg/kg) in physiological saline group, the heavy dose of group of Peltatin glucoside (100mg/kg), the Peltatin glucoside.Use 10% chloral hydrate anesthesia, the electrocardiogram(ECG of tracing the medication front and back with electrocardiograph changes.After bringing out the rat ventricular model with bariumchloride intravenous injection (4mg/kg), intravenous (IV) drug or equivalent physiological saline respectively, the ventricular arrest number appears in record.The results are shown in Table 3.
1.2 result
Peltatin glucoside can make bariumchloride induce rat ventricular to recover normal, compares P＜0.01 with the physiological saline group.
Table 3 Peltatin glucoside is to the influence of rat ventricular
| Medicine | Dosage (mg/kg) | Number of animals (only) | Ventricular arrest number (only) | Ventricular arrest rate (%) |
| N.S Peltatin glucoside Peltatin glucoside Peltatin glucoside lignocaine | 25 50 100 5 | 10 10 10 10 10 | 10 2 2 2 1 | 100 20* 20* 20* 10* |
* compare P＜0.01 with the physiological saline group
2. Peltatin glucoside function of resisting myocardial ischemia
2.1. method
2.1.1 dog expeirmental myocardial ischemia model preparation
Get adult healthy hybrid dog, body weight 10-15kg, intravenous injection 3% vetanarcol (30mg/kg) anesthesia, trachea cannula connects respirator, open chest and expose heart, separate and ligation anterior descending coronary root, place epicardial lead, be recorded in eight through bioelectric amplifier and lead physiograph, femoral arteriography is connected in eight through pressure transducer and leads physiograph.
2.1.2 experiment grouping
Experiment divides 5 groups, every group of 6 dogs, give distilled water respectively through duodenum, the heavy dose of 40mg/kg of Peltatin glucoside, dosage 20mg/kg in the Peltatin glucoside, the low dose of 10mg/kg of Peltatin glucoside, positive drug Diaoxinxuekang 100mg/kg, the administration volume is 0.5ml/kg, the operation finish the record normal value after administration, the record administration after 15,30,60,90,120,180 minutes parameters, with the summation (∑ ST) of each time point visceral pericardium ECG ST section lift-off value as the degree of myocardial ischemia index, the point that visceral pericardium ECG ST section lift-off value is surpassed 2mv is decided to be the ischemic point, calculate total ischemic count (NST), as myocardial ischemia scope index, write down HR and MBP simultaneously, represent myocardial consumption of oxygen with the product evolution of blood pressure and heart rate.The results are shown in Table 4
2.2 result
2.2.1 Peltatin glucoside is to the Electrocardiographic influence of dog visceral pericardium
Duodenum gives Peltatin glucoside, and the ST section of raising is obviously descended, and with comparison P＜0.05 before the administration, though the ST section of blank group has decline, with comparison there was no significant difference before the administration, sees Table 4.Duodenum gives Peltatin glucoside, and NST obviously reduces behind the 90min, with comparison P＜0.05 before the administration, though the NST of blank group has fluctuation, with comparison there was no significant difference before the administration, sees Table 5.
Table 4 Peltatin glucoside is to the influence (unit: mv) of dog visceral pericardium electrocardiogram(ECG ∑ ST
| Minute (min) | Model control group | Peltatin glucoside | Positive drug 100mg/kg | ||
| 10mg/kg | 20mg/kg | 40mg/kg | |||
| Before the normal value administration after the administration 15 30 60 90 120 180 | 15±8 235±85 230±86 236±110 236±100 240±123 250±130 210±93 | 14±9 243±70 240±52 205±65△ 200±70△ 192±50△ 190±35△ 198±40△ | 16±15 250±90 220±92 160±95* 152±50* 152±40* 130±30* 90±22* | 14±13 250±60 198±51 176±70* 150±65* 126±30* 120±25* 100±21* | 13±10 232±60 150±70 132±41* 153±51* 143±70* 142±75* 110±85* |
* with before the administration compare P＜0.01 △ and preceding relatively P＜0.05 of administration
Table 5 Peltatin glucoside is to the influence of dog visceral pericardium electrocardiogram(ECG NST
| Minute (min) | Model control group | Peltatin glucoside | Positive drug 100mg/kg | ||
| 10mg/kg | 20mg/kg | 40mg/kg | |||
| Before the normal value administration after the administration 15 30 60 90 120 180 | 1±1 27±3 28±4 26±4 27±4 27±5 28±3 26±4 | 1±1 26±4 26±5 25±6 25±7 24±7 24±8 24±6 | 1±1 26±5 24±6 23±4 23±6 24±5* 22±5* 22±4* | 1±1 27±3 23±6 21±7 21±6 20±3* 19±6* 19±7* | 1±1 28±3 22±4 25±5 25±5* 21±7* 21±7* 19±8* |
* with before the administration compare P＜0.01
2.2.2 Peltatin glucoside influences the myocardial oxygen consumption exponential
After giving the dog distilled water of myocardial ischemia, the myocardial oxygen consumption index increases (P＜0.05), show under acute cardiac ischemic condition, myocardial consumption of oxygen increases, but after duodenum gives Peltatin glucoside, increase is not seen in the increase of myocardial oxygen consumption index, shows that Peltatin glucoside can obviously suppress the increase of the oxygen-consumption that causes owing to myocardial ischemia.See Table 6.
Table 6 Peltatin glucoside influences myocardial ischemia dog myocardial oxygen consumption exponential
| Minute (min) | Model control group | Peltatin glucoside | Positive drug 100mg/kg | ||
| 10mg/kg | 20mg/kg | 40mg/kg | |||
| Before the normal value administration after the administration 15 30 60 90 120 180 | 125±12 122±13 125±8 126±7 127±6 125±11 125±6 124±10 | 125±10 124±9 122±8 122±10 123±8 124±6 120±7 122±5 | 125±12 123±5 120±7 119±4 122±6 123±5 124±9 123±4 | 124±12 122±6 115±6 114±7 112±6 113±13* 115±11* 117±7 | 125±10 124±3 119±4 119±5 118±5* 110±7* 112±7* 112±8* |
* with before the administration compare P＜0.01
3. Peltatin glucoside is to the influence of focal cerebral ischemia in rats
3.1 method
3.1.1 model preparation
Get body weight 220-240g big white mouse, use 10% chloral hydrate anesthesia, separate internal carotid artery, the tree lace of will sterilize inserts internal carotid artery, sews up the incision, and pulls out Outlet bolt behind the 3h, treats the rat administration afterwards of reviving.
3.1.2 animal grouping and administration
Get 80 of modeling success rats, random packet, every group 20, male and female half and half are divided into dosage group (50mg/kg), small dose group (25mg/kg), nimodipine group (1mg/kg) in physiological saline group, the heavy dose of group of Peltatin glucoside (100mg/kg), the Peltatin glucoside.Gastric infusion, 7d detects brain water content and brain infarction area after administration finishes continuously.
3.2 result
3.2.1 Peltatin glucoside is to the influence of brain water content
Control group operation side brain water content is apparently higher than other group (P＜0.05), and Peltatin glucoside group and nimodipine group brain both sides water content difference do not have significance.See Table 7.
Table 7 Peltatin glucoside is to the influence of rat cerebral tissue's water content
| Model control group | Peltatin glucoside | Nimodipine | |||
| 25mg/kg | 50mg/kg | 100mg/kg | |||
| Brain water content (%) | 85.5±0.50 | 83.5±0.20 | 81.3±0.20 | 79.0±0.40* | 80.0±0.20* |
* compare P＜0.05 with control group
3.2.2 Peltatin glucoside is to the influence of brain infarction area
The infarct kitchen range all appears in each treated animal, but Peltatin glucoside group and nimodipine group brain infarction area significantly reduce, and relatively there were significant differences (P＜0.01) with control group.See Table 8.
Table 8 Peltatin glucoside is to the influence of rat cerebral infarction area
| Model control group | Peltatin glucoside | Nimodipine | |||
| 25mg/kg | 50mg/kg | 100mg/kg | |||
| Brain water content (%) | 18.2±1.52 | 16.2±1.52 | 13.2±1.21 | 12.0±1.01* | 10.0±1.41* |
* compare P＜0.01 with control group
Four, conclusion
This result of study shows; Peltatin glucoside toxicity is lower; can obviously alleviate degree of myocardial ischemia and scope that the dog branch of coronary artery causes; reduce the myocardial oxygen consumption index; and can obviously resist bariumchloride inductive rat anti irregular pulse; also can reduce the brain infarction area of focal cerebral ischemia rat, the prompting Peltatin glucoside has the certain protection effect to cerebral ischemia and myocardial ischemia, and this research provides theoretical foundation for clinical application.
Can draw based on above result and the invention has the advantages that:
1. the preparation method of Peltatin glucoside of the present invention need not use deleterious organic solvent and silica gel column chromatography to separate, and output is big, and the cycle is long, and cost is low, and technology is simple, is fit to suitability for industrialized production.
2. the present invention has excavated new medicinal use to Ilex rotunda Thunb., has opened up a new Application Areas.
3. Peltatin glucoside safety non-toxic of the present invention, pharmacological action is strong, good drug efficacy, indicating has good prospect in medicine.
4. product preparation process of the present invention is simple, does not see toxic side effect.Both can make oral preparations such as oral preparations such as tablet, dripping pill, capsule; Also can make injection formulations such as powder injection, instillation etc.
5. the medicine that product of the present invention is made can obviously alleviate degree of myocardial ischemia and the scope that the dog branch of coronary artery causes, reduce the myocardial oxygen consumption index, and can obviously resist bariumchloride inductive rat anti irregular pulse, also can reduce the brain infarction area of focal cerebral ischemia rat, these effects have shown that its anti-arrhythmia, myocardial ischemia, cerebral ischemia effect are remarkable.Be used for clinically the prevention and the treatment coronary heart disease, the obstruction of qi in the chest of stenocardia and extravasated blood internal resistance, dizzy, breathe hard, palpitaition, uncomfortable in chest or the pain; Apoplexy, cerebral infarction are waited indefinitely.
Embodiment
Below will describe several embodiments of the present invention, but content of the present invention is not limited to this fully.
Embodiment 1: get Ilex rotunda Thunb. meal 2000g, with 6 times 80% alcohol reflux three times, extracted respectively 2,1,1 hours, filter, filtrate merges, and is concentrated into the medicinal extract shape, adds water 6000ml, and heating in water bath stirs, and standing over night filters, throw out and filtrate.Throw out adds the 50-95% alcohol reflux, filters, and filtrate is concentrated, places, and filters, and drying precipitate gets total saponins, and total saponins adds 10-100 50-95% alcohol crystal doubly, gets a part of Peltatin glucoside.Filtrate is concentrated into 1000ml, put and be chilled to room temperature, filter, throw out is given a baby a bath on the third day after its birth time with suitable quantity of water, drying, the 50-95% alcohol crystal of doubly measuring with 10-50, make another part Peltatin glucoside coarse-grain again, the Peltatin glucoside that makes for twice merges, and the 50-95% ethanol of doubly measuring with 10-100 is recrystallization repeatedly, the pure product of Peltatin glucoside.Yield 3.85% is measured in accordance with the law, and content is 98.59%.
Embodiment 2:
Get the Peltatin glucoside of the method preparation of embodiment 1, take infusion solution preparation method well-known in the art, be prepared into Peltatin glucoside sodium chloride injection and Peltatin glucoside glucose injection: Peltatin glucoside 40mg, sodium-chlor 2.25g, make the Peltatin glucoside sodium chloride injection, its specification is 500ml, intravenous injection, each 1 bottle, once a day; Peltatin glucoside 40mg, glucose 12.5g makes the Peltatin glucoside glucose injection, and its specification is 500ml, intravenous injection, each 1 bottle, once a day.
Embodiment 3: get the Peltatin glucoside 20g by the method preparation of embodiment 1, add proper amount of water for injection, transfer pH value to 7 with yellow soda ash, stirring and dissolving adds the N.F,USP MANNITOL that is equivalent to Peltatin glucoside 10-15% amount injection again, degerming filters, measure content, 1000 of packing, 20mg/ props up, seal, promptly.Intravenous injection, each 40mg, once a day.
Embodiment 4:
Get Peltatin glucoside 300g, the 10% HPMC 32ml of the preparation of embodiment 1 method.Take capsule preparation method thereof well-known in the art, make 1000 capsules, every contains Peltatin glucoside 300mg.Oral, each 1, every day 1 time.
Embodiment 5: Peltatin glucoside 300g, the lactose 68g, starch 60g, the talcum powder 20g that get the preparation of embodiment 1 method.Take method for preparing tablet thereof well-known in the art, mix all components in appropriate vessel, make particle, add Magnesium Stearate 2g again, mixing with standard concave stamping in 9/32 o'clock, is made 1000, (every contains Peltatin glucoside 300mg).Oral, each 1, every day 1 time.
Claims (9)
1. Peltatin glucoside for the treatment of diseases of cardiovascular and cerebrovascular systems, available following method preparation:
The Ilex rotunda Thunb. extraction using alcohol, extract adds water, and is centrifugal, gets throw out and supernatant liquor.Throw out adds the 50-95% alcohol reflux, filtration, and filtrate concentrates, and places, and filters, and drying precipitate gets a part of total saponins, and the total saponins alcohol crystal gets a part of Peltatin glucoside.Supernatant concentration, centrifugal, throw out is used alcohol crystal with an amount of washing, dry back, makes another part Peltatin glucoside again.The Peltatin glucoside that makes for twice merges, with ethanol recrystallization repeatedly, the pure product of Peltatin glucoside.
2. Peltatin glucoside according to claim 1, it is characterized in that: get the Ilex rotunda Thunb. meal, with 2-10 50-95% alcohol reflux doubly three times, each 1-3 hour, united extraction liquid, be concentrated into the medicinal extract shape, add 3-10 water doubly, heating, stir, standing over night, centrifugal, get throw out and supernatant liquor.Throw out adds the 50-95% alcohol reflux, filters, and filtrate is concentrated, places, and filters, and drying precipitate gets a part of total saponins, and total saponins adds 10-100 50-95% alcohol crystal doubly, gets a part of Peltatin glucoside.Supernatant concentration is to 1/2-2 times of volume, put and be chilled to room temperature, centrifugal, throw out is given a baby a bath on the third day after its birth time with suitable quantity of water, drying, the 50-95% alcohol crystal of doubly measuring with 10-100, make another part Peltatin glucoside coarse-grain again, the Peltatin glucoside that makes for twice merges, and the 50-95% ethanol of doubly measuring with 10-100 is recrystallization repeatedly, the pure product of Peltatin glucoside.
3. Peltatin glucoside according to claim 2 is characterized in that: with 2-10 50-95% alcohol reflux doubly, extracting solution is concentrated into medicinal extract, adds water, and is centrifugal, gets throw out and supernatant liquor.Throw out adds the 50-95% alcohol reflux, filtration, and filtrate concentrates, and places, and filters, and drying precipitate gets a part of total saponins, and total saponins adds alcohol crystal, gets a part of Peltatin glucoside.Supernatant concentration, centrifugal, throw out is given a baby a bath on the third day after its birth inferior with suitable quantity of water, dry, with the 50-95% alcohol crystal that 10-100 doubly measures, make another part Peltatin glucoside coarse-grain again, the Peltatin glucoside that makes for twice merges, the 50-95% ethanol of doubly measuring with 10-100 is recrystallization repeatedly, the pure product of Peltatin glucoside.Its content is greater than 98.0%.
4. the pharmaceutical composition that is used for the treatment of diseases of cardiovascular and cerebrovascular systems is for containing each the Peltatin glucoside and the pharmaceutically acceptable carrier of claim 1-3 for the treatment of significant quantity.
5. pharmaceutical composition according to claim 4 is characterized in that: be made up of Peltatin glucoside and oral preparations auxiliary material and injection auxiliary material basically; Be pill, oral liquid, injection liquid, instillation, lyophilized powder, microcapsule, capsule, tablet or various slowly-releasing or quick-release tablet.
6. preparation of drug combination method according to claim 5 makes with following steps: taking polyethylene glycol 6000 and/or Macrogol 4000 are in 90-100 ℃, and mixed melting adds Peltatin glucoside and mixes, and routine is made dripping pill.
7. preparation of drug combination method according to claim 6, it is characterized in that: by weight, taking polyethylene glycol 6000 and/or Macrogol 4000 1-4 part are behind 90-100 ℃ of mixed melting, add Peltatin glucoside raw material 1-2 part and mix, routine is made dripping pill.
8. preparation of drug combination method according to claim 5 makes with following steps: get Peltatin glucoside, add the 5-25% polyglycol solution, heating in water bath makes dissolving, puts coldly, with 5-25% polyoxyethylene glycol (400) solution dilution, is made into injection liquid.
9. preparation of drug combination method according to claim 8, it is characterized in that: get Peltatin glucoside 160mg, add 5-25% polyglycol solution 500ml dilution, just dissolve with 80 ℃ of heating in water bath, put cold, filter, add 5-25% polyoxyethylene glycol (400) solution, be made into the 2000ml injection liquid.
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