CN1111412C - Thrombus clearing soft capsule and preparation technology thereof - Google Patents

Abstract

The present invention relates to an oral medicine soft capsule and a preparation technique thereof. The product is composed of the two parts of physic liquor and a capsule shell. The present invention is characterized in that every grain of the physic liquor contains 40 to 250 milligrams of notoginseng triterpene by weight and also contains solvent and stabilizers; the capsule shell contains 10 shares by weight of gelatin, 3.25 to 3.35 shares by weight of glycerol and preservative. The present invention has the advantages that a thrombosis elimination soft capsule which takes notoginseng triterpene as a main effective constituent and a preparation technique thereof are provided, the product series oral administration dosage form can overcome the defects of the existing dosage forms, bioavailability is high, and the standards of the dosage form in the aspects of appearance, hardness, disintegration degree, physical and chemical stability, etc. are met.

Description

Notoginseng total saponin capsule and preparation technology thereof

Technical field

The present invention relates to contain the soft capsule oral drugs and the preparation technology thereof of Radix Notoginseng total arasaponins effective dose.

Background technology

Radix Notoginseng total arasaponins (Panax Notoginseng Saponins) is total Saponin that the reed head of araliaceae ginseng plant Radix Notoginseng (Panax Notoginseng (Burk.) F.H.Chen) extracts by certain technology, be faint yellow indefiniteness powder, bitter but slightly sweet taste, soluble in water, methanol, ethanol, be insoluble in acetone, ether and benzene, easily the moisture absorption.Have blood circulation promoting and blood stasis dispelling, promote blood circulation active, the effect of anticoagulant and cerebral blood flow increasing amount.Be used for apoplexy sequela, central retinal vein occlusion, hyphema etc.Radix Notoginseng total arasaponins toxicity is low, and side effect is minimum.

" XUESAITONG ZHUSHEYE " that with Radix Notoginseng total arasaponins be main effective ingredient has better curative effect to the paralysis of cerebral infarction and apoplexy sequela performance, and be harmless to the heart, liver,kidney,spleen stomach function regulating function, also do not have obvious toxic-side effects.With Radix Notoginseng total arasaponins is that the oral formulations of main effective ingredient has hard capsule, electuary, tablet.Existing oral formulations such as tablet and hard capsule, wherein effective ingredient Radix Notoginseng total arasaponins dissolution velocity in aqueous medium is slower, the conglomeration of easily being clamminess in the course of dissolution, luming, dissolving is relatively more difficult again; And main effective ingredient such as Rb1 and Rg1 equimolecular quantity are bigger in the Radix Notoginseng total arasaponins, and digestive tract absorbs slow and few, and principal agent excretes through feces in a large number, and bioavailability is low.Therefore existing oral formulations can't reach ideal effect to apoplexy, angina pectoris etc., only can be with building body, blood fat reducing, improve health care such as cardiovascular disease and be applied to clinical.The clinical use of injection is convenient not as oral formulations, and safety is not as oral formulations.The Chinese medicine that pollutes of commute particularly is though also be difficult to guarantee the stable of its effective ingredient through sterilization.Quality problems such as variable color, crystallization or precipitation just often appear in " XUESAITONG ZHUSHEYE " product of existing many producers.Have research data to show in addition, cardiovascular patient is comparatively responsive to metal ions such as sodium ion, and particularly a large amount of sodium ion can limit the Clinical Application scope.Sodium ion is just arranged in the XUESAITONG ZHUSHEYE.Moreover the frangible rapid wear of aqueous injection ampoule, can freeze winter in the north.

Summary of the invention

The purpose of this invention is to provide a kind of is the notoginseng total saponin capsule and the preparation technology thereof of main effective ingredient with Radix Notoginseng total arasaponins, product is an oral administered dosage form, can overcome the shortcoming of existing dosage form, the bioavailability height satisfies the standard of such dosage form aspect outward appearance, hardness, disintegration etc. and physical and chemical stability.

Product of the present invention is made of medicinal liquid and softgel shell two large divisions, it is characterized in that medicinal liquid by weight every contain Radix Notoginseng total arasaponins 40-250 milligram, and contain solvent 250-400 milligram, stabilizing agent 200-500 milligram, the gelatin that contains 10 parts of weight in the softgel shell, 3.25-3.35 the glycerol of part weight, and antiseptic.

Solvent is one or more in liquid polyethylene glycol, isopropyl alcohol, tween 80, glycerol, propylene glycol, water and the vegetable oil.

Antiseptic is one or more in glycerol, propylene glycol, methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, the P-hydroxybenzoic acid phenyl ester

But one or more in stabilizing agent water, glycerol, tween 80, ethyoxyl castor oil hydrogenated (GremophorRH 40), soybean lecithin, Cera Flava, aluminum monostearate, ethyl cellulose, the solid polyethylene glycol.

Gelatin, glycerol proportioning are difficult to grasp in the prescription of softgel shell.The amount of glycerol is too many, and softgel shell is softer, than being easier to extrusion; The amount of glycerol very little, softgel shell is harder, crisp, influences the quality stability and the disintegration time of soft capsule.We have carried out detailed experimental study to the gelatin of softgel shell, the proportioning of glycerol, have obtained a proportioning preferably at last.

An amount of gelatin is added in the rustless steel glue pot, add suitable quantity of water again, airtight, 70 ℃ are incubated 3 hours, add glycerol, the antiseptic of test consumption more respectively, stir, vacuumize degassing 2 hours, put into 70 ℃ of insulations of gelatin heat-preserving container standing over night, second day, the moulding ball, drying at room temperature, keep sample and investigate three months, examination softgel shell outward appearance and physical property, the result is as follows:

The index content of the test	Gelatin 30kg glycerol 3.0kg	Gelatin 10kg glycerol 3.2kg	Gelatin 10kg glycerol 3.25-3.35kg	Gelatin 10kg glycerol 3.4kg	Gelatin 10kg glycerol 3.6kg
						Softgel shell outward appearance and physical property	Too firmly, easily crisp	Too firmly, easily crisp	Suitable	Softer, the easy moisture absorption	Softer, the easy moisture absorption

Illustrate: the softgel shell prescription that is filtered out is applicable to the place of warm moist.

By above test, can reach a conclusion, should contain 10 parts in gelatin in the prescription of softgel shell, glycerol 3.25-3.35 part (weight ratio)

Every of soft gelatin capsule contains principal agent---and the amount of Radix Notoginseng total arasaponins is determined; Consider the size of economic factor and selected every ball easy to prepare, finally can determine the liquid formula of embodiment.

Contain in the optimum formula of product of the present invention: component amount (gram/grain) Radix Notoginseng total arasaponins 0.04-0.25 solvent 0.25-0.40 stabilizing agent 0.02-0.05

The preparation technology of notoginseng total saponin capsule may further comprise the steps:

Technology 1: after Radix Notoginseng total arasaponins beaten powder and cross the 80-120 mesh sieve, by joining in the liquid polyethylene glycol, heating made the solution insulation at 50-70 ℃ and stir and make its dissolving under stirring, add entry and glycerol etc. after the dissolving, stirring makes its mix homogeneously, filter, outgas back pelleting, drying, promptly.

Technology 2: after Radix Notoginseng total arasaponins beaten powder and cross the 80-120 mesh sieve, feed intake by the prescription proportioning, earlier with the stabilizing agent thermosol in partial solvent, the thermosol thing is added in the residual solvent that is preheating to 35-45 ℃ lentamente, the limit edged stirs again, and then various solids are added one by one, fully mix each back that adds, moistening fully to guarantee, cross colloid mill and pulverize back pelleting, drying, promptly.

This product is the yellow transparent soft capsule.

It is the notoginseng total saponin capsule and the preparation technology thereof of main effective ingredient with Radix Notoginseng total arasaponins that good effect of the present invention has provided a kind of, product is an oral administered dosage form, can overcome the shortcoming of existing dosage form, the bioavailability height satisfies the standard of such dosage form aspect outward appearance, hardness, disintegration etc. and physical and chemical stability.

The specific embodiment

The present invention is by above-mentioned prepared, and its detailed component is provided by the following example, but protection scope of the present invention is not limited to this.

An amount of capsule shells 0.17 of embodiment 1 component amount (gram/grain) Radix Notoginseng total arasaponins 0.1 Polyethylene Glycol, 0.33 glycerol, 0.023 water

An amount of capsule shells 0.19 of embodiment 2 component amount (gram/grain) Radix Notoginseng total arasaponins 0.15 isopropyl alcohol, 0.35 ethyoxyl castor oil hydrogenated, 0.04 glycerol, 0.03 water

Embodiment 3 component amounts (gram/grain) an amount of capsule shells 0.14 embodiment of total saponin 0.05 polyethylene glycol of pseudo-ginseng 0.27 ethyoxyl rilanit special, 0.041 glycerine, 0.04 water 4 component amounts (gram/grain) an amount of capsule shells 0.19 of pseudo-ginseng total saponin 0.2 liquid polyethylene glycol 0.4 solid polyethylene glycol, 0.018 glycerine, 0.03 water

Embodiment 5 component amounts (gram/grain) an amount of capsule shells 0.15 of pseudo-ginseng total saponin 0.1 corn oil 0.30 soybean lecithin, 0.01 beeswax, 0.03 water

Embodiment 6 component amounts (gram/grain) an amount of Tween-80 0.003 soya-bean oil 0.17 soybean lecithin, 0.006 ethyl cellulose (100cps) of total saponin 0.05 water of pseudo-ginseng 0.025 capsule shells 0.12

The composition of capsule (shell) the epithelium liquid of embodiment 1 to 4:

Gelatin 100kg

Glycerol 35kg

Water is an amount of

Methyl parahydroxybenzoate 0.22kg

Propyl p-hydroxybenzoate 0.055kg

The composition of capsule (shell) the epithelium liquid of embodiment 5 to 6:

Gelatin 100kg

Glycerol 33kg

Water is an amount of

Ethylparaben 0.25kg

The preparation technology of embodiment is:

Technology 1: after Radix Notoginseng total arasaponins beaten powder and cross 100 mesh sieves, join gradually under stirring in the liquid polyethylene glycol, heating makes the solution insulation about 60 ℃ and stir and make its dissolving, add entry and glycerol etc. after the dissolving, stirring makes its mix homogeneously, filter, outgas back pelleting, drying, promptly.Perhaps:

Technology 2: after Radix Notoginseng total arasaponins beaten powder and cross 100 mesh sieves, feed intake by the prescription proportioning.Earlier with the stabilizing agent thermosol in an amount of fluid matrix, the thermosol thing is added lentamente in the residue substrate that is preheating to 40 ℃ again, the limit edged stirs, and then various solids such as principal agent are added one by one, fully mix each back that adds, moistening fully to guarantee, cross colloid mill and pulverize back pelleting, drying, promptly.

According to the requirement under new drug (Chinese medicine) the stability test capsule item, to notoginseng total saponin capsule three batch samples room temperature condition, and illumination (is according to 240 hours under the 2800LX in illuminance) and humidity effect factor carried out the quality observation, and measured every data, the result is as follows:

Table 1 970125-1 criticizes the room temperature preliminary result of investigation that keeps sample

Keep sample the time (moon)	Outward appearance	Thin layer chromatography	Disintegration (minute)	Rb1 content (%)	Rg content (%)	Total saponin content (%)
							0	Complete soft gelatin capsule includes yellow clear and bright thick liquid	Principal spot is consistent with reference substance	6.5	37.52	28.48	100.05
1	The same	The same	8	37.40	28.21	99.68
							3	The same	The same	9.5	37.22	28.07	99.07
6	The same	The same	15	37.01	27.74	98.89
							12	The same	The same	17	36.84	27.51	98.02

Table 2 970125-2 criticizes the room temperature preliminary result of investigation that keeps sample

Keep sample the time (moon)	Outward appearance	Thin layer chromatography	Disintegration (minute)	Rb1 content (%)	Rg1 content (%)	Total saponin content (%)
							0	Complete soft gelatin capsule includes yellow clear and bright thick liquid	Principal spot is consistent with reference substance	6.5	36.02	29.73	97.82
1	The same	The same	7	35.86	29.63	97.53
							3	The same	The same	8.5	35.75	29.11	97.22
6	The same	The same	14	35.90	28.90	97.59
							12	The same	The same	17	35.01	27.81	96.24

Table 3 970125-3 criticizes the room temperature preliminary result of investigation that keeps sample

Keep sample the time (moon)	Outward appearance	Thin layer chromatography	Disintegration (minute)	Rb1 content (%)	Rg1 content (%)	Total saponin content (%)
							0	Complete soft gelatin capsule includes yellow clear and bright thick liquid	Principal spot is consistent with reference substance	7	35.09	29.03	98.61
1	The same	The same	7	34.87	28.54	98.24
							3	The same	The same	9	34.94	28.48	98.42
6	The same	The same	14	34.38	28.61	97.98
							12	The same	The same	18	34.06	28.32	96.79

Table 4 light is to the influence of notoginseng total saponin capsule

Lot number	Outward appearance	Thin layer chromatography	Disintegration (minute)	Rb1 content (%)	Rg1 content (%)	Total saponin content (%)
							970125 -1	Complete soft gelatin capsule includes yellow clear and bright liquid	No change	15	36.91	28.03	99.22
970125 -2	The same	The same	13	35.77	29.32	97.36
							970125 -3	The same	The same	14	34.80	28.19	98.23

Table 5 humidity is to the influence of notoginseng total saponin capsule

Project condition lot number	Outward appearance	Thin layer chromatography	Disintegration (minute)	Rb1 content (%)	Rg1 content (%)	Total saponin content (%)
							25 ℃ of RH75% 970125-2 of 970125-1 (sealing) 970125-3	Complete soft gelatin capsule, it is the same to include yellow clear and bright thick liquid	No change no change no change	10 10 9	37.28 35.82 34.91	28.31 29.28 28.66	99.81 97.43 98.19
25 ℃ of RH90% 970125-2 of 970125-1 (sealing) 970125-3	Complete soft gelatin capsule, it is the same to include yellow clear and bright thick liquid	No change no change no change	12 12 10	37.03 35.23 34.41	28.14 28.72 27.84	99.89 97.24 97.52

Annotate: be defined as the disintegration of soft capsule: 1 hour with interior (64 pages of two appendix of in 1995 version of Chinese Pharmacopoeia).Content is limited to 90-110%.

The present invention is by its performance of following evidence: one, animal acute toxicity test

Material:

1, notoginseng total saponin capsule: every ball contains Radix Notoginseng total arasaponins 100mg.Research and development centre of Kunming Medicine Stock Co., Ltd provides, lot number: the 970125-2. heating, and the adding distil water dissolved dilution is to required dosage concentration, and 38 ℃ of water-soluble constant temperature are standby:

2, laboratory animal: the ICR mice is provided by Yunnan Province natural drug pharmacology key lab, (Yun Weidong manages A12 number) male and female half and half, and W:19-21g, it is identical with the common mice in this chamber to observe feeding environment.

Test method and dosage regimen:

Sun Shi improvement Kou Shi composite accounting design dosage regimen is pressed in prerun before the formal test, is divided into five groups, press 0.4ml/10g and irritate stomach, successive administration is 2 times in the 6h, medicinal liquid 0.8 proportional diluted, 2 dosages of maximal dose group are 10g/kg, animal random packet, 10 every group, medicine front 2h stops eating, normal breeding observing behind the medicine, and record poisoning manifestations and death condition, dead animal cuts open inspection, the toxic pathological changes of each main organs of perusal, surviving animals continues one week of breeding observing.

Result of the test:

In the 6h part animal dead is arranged promptly after the high dose group administration for the first time, animal dead mostly occurs in 24h behind the medicine, and part animal loose stool is not taken food calmness.Dead animal the intestines and stomach topping up, inflation, mesentery hyperemia.48h not dead animal can healthy survival, recovers normal in the week day by day, administration situation and the results are shown in following table:

Notoginseng total saponin capsule acute toxicity test in mice (ig)

Group dosage (mg/kg) number of animals (only) death toll (only) survival number (only) 1 10,000 10 912 8,000 10 733 6,400 10 554 5,200 10 285 4,100 10 0 10

LD50=6730mg/kgLD50 95% credible 6730 ± 1260mg/kg two, the long-term toxicity test for animals of being limited to

Material and method:

1, medicine: notoginseng total saponin capsule is provided by Kunming Medicine Stock Co., Ltd, lot number: 970125-1, and specification is the 100mg/ ball, every 045ml contains principal agent 100mg.

2, animal: 80 of SD rats, male and female half and half provide (Yun Weidong manages A12 number) by Yunnan Province natural drug pharmacology key lab.

3, method: animal is divided into 4 groups at random, 20 every group, male and female half and half, sub-cage rearing is observed a week before the dispensing, treats that situations such as each treated animal activity, feed, feces are all no abnormal, begins dispensing then.

(1) small dose group: press 150mg/kg/ day administration.

(2) dosage group in: press 450mg/kg/ day administration.

(3) heavy dose of group: press 750mg/kg/ day administration.

(4) matched group: give blank solvent.

Above-mentioned four groups all by 0.3375ml/100g, every morning is irritated stomach once, amounts to 56 days, not drug withdrawal of centre.

Inspection item: weigh weekly, and adjust dosage thereupon, cage is looked on and is examined just character etc. of fur, eye, nose, mucosa, breathing, behavior, activity, feed, drinking-water and two; After medication finished, five hematological indices were checked in blood sampling: erythrocyte (RBc), leukocyte (WBc), platelet (PLT), hematochrome (Hb) and leukocyte differential count;

11 blood parameters: alanine aminotransferase (ALT), serum glutamic oxalacetic transaminase (AST), total serum protein (TP), serum urea nitrogen (BUN), creatinine (Crea), T-CHOL (T-CHO), blood glucose (Glu), albumin (ALB).

AST/ALT, A/G; 2/3 animal does the pathology inspection; System's postmortem; The heart, liver, spleen, lung, kidney device coefficient; Brain, the heart, liver, spleen, lung, kidney, adrenal gland, thymus, ovary, testis, uterine cancer cell are learned the animal of light microscopy checking and 1/3 and are retained 2 weeks of observation.

Result of the test:

1, each dosage group of notoginseng total saponin capsule and blank solvent matched group are all movable normal in 56 day experimental period, and behavior is active, and the hair color smoothness does not see that feces is unusual, none death.

2, four treated animal body weight gain situation basically identicals.

3, hematological examination, each dosage group of notoginseng total saponin capsule and matched group be the indifference opposite sex relatively all.

4, blood biochemical detects, and male Mus ALT is higher than the matched group except that low dose, and all the other and matched group be the indifference opposite sex relatively all.

5, the brain of four treated animals, the heart, spleen, lung, kidney, the adrenal gland, thymus, ovary, testis, 11 kinds of internal organs outward appearances such as uterus are normal, and pathological anatomy and histopathologic examination all do not have special pathological change.

Notoginseng total saponin capsule adult's consumption 15mg/kg/ day, in view of the above, the rat long term toxicity test, large, medium and small dosage is equivalent to 50,30 of the consumption of being grown up respectively.And 10 times, so adopt the 1/50 heavy dose of upper limit as clinical application, promptly 15mg/kg/ day is safe.

In view of this product mice LD50 (6730mg/kg) is more than 400 times of clinical recommended dose, the every index of long term toxicity test was no abnormal in 56 days, exempted to do the pathology inspection so retain animal, and can exempt to do the long term toxicity test of dog.

Three, the main pharmacodynamics of notoginseng total saponin capsule experiment:

Experiment material:

(1) medicine: notoginseng total saponin capsule (Kunming Medicine Stock Co., Ltd, lot number: 970125, get capsule psychological treatment liquid during experiment and dilute), XUESAITONG ZHUSHEYE (Kunming Medicine Stock Co., Ltd, lot number: 970351-07) with normal saline

(2) animal: mice, the Kunming kind, rat, the SD kind, all available from Yunnan Province natural drug pharmacology key lab rabbit, male and female half and half, 2.0-3.0kg is available from animal section of unming Medical College.

(3) other: 722 type visible spectrophotometers, BS-631 type platelet aggregation instrument, MP120-1 type electronic balance, reagent are analytical pure or medicinal specification (wherein, platelet activating factor and arachidonic acid are Sigma company product, and adenosine diphosphate (ADP) is Switzerland's import packing).

Experimental technique

(1) cerebral ischemia protection experiment

1, the reference literature method prepares imperfection cerebral ischemic model (the ligation common carotid artery merges voltage drop method): use the nembutal anesthetized rat, isolate left and right sides carotid artery and femoral artery.Connect blood pressure measuring device, ligation left and right sides common carotid artery also is depressurized to 5.3-6.00kPa (40-45mmHg) (the also not blood-letting of not ligation of Sham-operated control group tremulous pulse) from the femoral artery blood-letting, after keeping this blood pressure to make cerebral ischemia 30min, blood is refilled rat and recover the brain perfusion, this moment, the Mus brain both suffered ischemic injuries, also produced reperfusion injury.

(1) mensuration of brain water content after the cerebral ischemia: (264 ± 17g) are divided into 5 groups at random to get 55 of male rats, test preceding 6 hours oral administration gavages and be subjected to reagent thing (Sham-operated control group and the commensurability normal saline of cerebral ischemic model group filling stomach, down together), gastric infusion is once again during experiment, both be equipped with ischemia model by last legal system, duodenal administration is once again after recovering hemoperfusion, broken end is got forebrain after 3 hours, weigh, put 110 ℃ and bake, calculate brain water content % (brain water content %=(weight in wet base one dry weight)/weight in wet base * 100%) to constant weight.

(2) mensuration of cerebral ischemia hindbrain capillary permeability: get 55 (244 ± 16g of rat, male and female half and half), be divided into 5 groups at random, test preceding 6 hours oral administration gavages and be subjected to the reagent thing, gastric infusion is once again during experiment, be equipped with ischemia model by last legal system, the blue 60mg/kg of the respectively quiet notes ivens of 10min before the ligation common carotid artery, duodenal administration is once again after recovering hemoperfusion, broken end is got forebrain after 5 hours, weighs, and puts in the formamide solution, at 632nm place survey trap with spectrophotometer at 45 ℃ of following incubations after 60 hours, calculate the content (the wet brain of ug/g is heavy) of ivens orchid in the brain according to standard curve.

(3) inspection of cerebral ischemia hindbrain tectology: get 20 (259 ± 19g of rat, male and female half and half), be divided into 5 groups at random, test preceding 6 hours oral administration gavages and be subjected to the reagent thing, gastric infusion is once again during experiment, be equipped with ischemia model by last legal system, duodenal administration once breaks end after 3 hours and gets forebrain again after recovering hemoperfusion, formalin fixed, crown section, HE dyeing, the light border is checked.

2, anoxia enduring experiment under the mice normal pressure: get 56 (23.8 ± 1.8g of mice, male and female half and half), be divided into 4 groups at random, distinguish twice of gastric infusion in preceding 6 hours of experiment and 30min, mice is put (connecting an adjust blood pressure bottle makes pressure equate with extraneous) in the glass exsiccator that sodica calx is housed, airtight and timing, the record anoxia in mice death time.

3, mice broken end posttension cause for gossip is tested: get 64 of male mices (24.2 ± 1.7g), be divided into 4 groups at random, gastric infusion twice respectively when preceding 6 hours of experiment and 30min during experiment is cut mice Mus head, immediate record is dehisced the time of breathing.

(2) anticoagulation experiment

1, clotting time influence experiment: get 60 of mices (23.8 ± 1.7g, male and female half and half), be divided into 5 groups at random,, pluck eyeball during experiment and get blood and measure clotting time with capillary tube method in preceding 6 hours of experiment and 30min gastric infusion twice respectively.

2, platelet aggregation influence experiment: carry out experiment in vitro by the BronShi turbidimetry, adopt Sanguis Leporis seu oryctolagi and prepare platelet count to 5 * 10 among platelet rich plasma (PRP) and platelet poor plasma (PPP) the adjusting PRP ⁸Cell/L, taking liquid mixes with FRP respectively, incubation 20min, add derivant platelet activating factor (PAF) (final concentration is 7.2nmlo/L) respectively, arachidonic acid (AA) (final concentration is 0.35mmol/L), adenosine diphosphate (ADP) (ADP) (final concentration is 3umlo/L) induced platelet is assembled, and measures the maximum percentage rate of assembling of platelet with platelet aggregation instrument, and calculates the platelet aggregation inhibition rate of medicine.

Above-mentioned experimental data represents that with X ± SD all experimental result is all carried out statistical analysis with method of analysis of variance.The result:

1, notoginseng total saponin capsule to cerebral ischemia after the influence of brain water content

Cerebral ischemic model group brain water content and sham operated rats relatively have significant difference, and brain water content obviously raises, notoginseng total saponin capsule (200,100mg/kg, po) with XUESAITONG ZHUSHEYE (60kg; Brain water content obviously descends after iv) all making cerebral ischemia, alleviates cerebral edema.Simultaneously, notoginseng total saponin capsule also demonstrates tangible dose-effect relationship.

2, notoginseng total saponin capsule to cerebral ischemia after cerebrovascular permeability influence in the cerebral ischemic model group cerebral tissue blue content of ivens and the apparent in view rising of sham operated rats, this presentation of results cerebral ischemia can make cerebrovascular permeability raise, notoginseng total saponin capsule (100,200mg/kg, po) with XUESAITONG ZHUSHEYE (60mg/kg; The blue content of ivens is obviously descended, illustrate that this two medicine can suppress the rising of cerebrovascular permeability after the cerebral ischemia.

3, notoginseng total saponin capsule is to the influence of cerebral ischemia hindbrain tectology

Visible Sham-operated control group rat brain neurocyte and neurogliocyte form are normal under the border, nuclear membrane is clear, kernel is obvious, bright or light the dying of endochylema, after birth is clear, obvious pathological change appears in cerebral ischemic model group rat cerebral tissue, at forehead, top, cortex of temporal lobe and Hippocampus etc. are located visible neurocyte karyopycnosis and (dwindle triangular in shape, engrain, kernel disappears), (nuclear structure is light to be dyed in karyolysis, disappear, the nuclear profile is unclear), the neurocyte at these positions is more than half ischemic necrosis to occur and neurocyte takes off changes such as mistake, and other sees the obvious swelling of neurogliocyte, between matter vasodilation hyperemia, the loose edema of a matter is obvious.Notoginseng total saponin capsule (100,200mg/kg, po) group and XUESAITONG ZHUSHEYE (60mg/kg; Iv) organize ischemias variations such as the karyopycnosis of cerebral tissue neurocyte, karyolysis and compare obvious reduction with the cerebral ischemic model group; it is dead to have only the only a few neurocyte to occur; matter was loose between neurogliocyte swelling reached also obviously alleviates, and presents tangible ischemia protective effect.

4, notoginseng total saponin capsule is to the influence of mice normal pressure hypoxia-bearing capability

Give notoginseng total saponin capsule (200mg/kg, po) and XUESAITONG ZHUSHEYE (120mg/kg; The effect of obvious prolongation mice time-to-live is iv) all arranged.

5, notoginseng total saponin capsule is to the influence of mice broken end back mouth breathing time

Give notoginseng total saponin capsule (200mg/kg, po) and XUESAITONG ZHUSHEYE (60mg/kgiv) effect that prolongs the mice mouth breathing time is all arranged.

6, notoginseng total saponin capsule is to the influence of clotting time of mice

Give notoginseng total saponin capsule (200mg/kg, po) and XUESAITONG ZHUSHEYE (120mg/kg; The effect that prolongs clotting time is iv) all arranged.

7, notoginseng total saponin capsule is to the influence of platelet aggregation

Notoginseng total saponin capsule can significantly suppress the inductive platelet aggregation of PAF in the concentration range of 0.625-2.5mg/ml, suppression ratio reaches 15.4-88.5%, when the concentration of 2.5mg/ml, can significantly suppress the inductive platelet aggregation of ADP, suppression ratio reaches 39.5%, XUESAITONG ZHUSHEYE also has remarkable inhibitory action to PAF and the inductive platelet aggregation of ADP in the 0.625-2.5mg/ml scope, suppression ratio reaches 8.0-75.1% and 20.9-33.9%.

Claims (5)

1, a kind of notoginseng total saponin capsule, constitute by medicinal liquid and softgel shell two large divisions, it is characterized in that medicinal liquid by weight every contain Radix Notoginseng total arasaponins 40-250 milligram and contain solvent 250-400 milligram, stabilizing agent 200-500 milligram, the gelatin that contains 10 parts of weight in the softgel shell, 3.25-3.35 the glycerol of part weight, and antiseptic.

2, as the said notoginseng total saponin capsule of claim 1, it is characterized in that: solvent is one or more in liquid polyethylene glycol, isopropyl alcohol, tween 80, glycerol, propylene glycol, water and the vegetable oil.

3, as the said notoginseng total saponin capsule of claim 1, it is characterized in that: antiseptic is one or more in glycerol, propylene glycol, methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, the P-hydroxybenzoic acid phenyl ester.

4, as the preparation technology of the said notoginseng total saponin capsule of claim 1, it is characterized in that may further comprise the steps: after Radix Notoginseng total arasaponins is beaten powder and crossed the 80-120 mesh sieve, under stirring, join in the liquid polyethylene glycol gradually, heating makes the solution insulation also stir at 50-70 ℃ and makes its dissolving, add entry and glycerol etc. after the dissolving, stirring makes its mix homogeneously, filter, outgas back pelleting, drying, promptly.

5, as the preparation technology of the said notoginseng total saponin capsule of claim 1, it is characterized in that may further comprise the steps: after Radix Notoginseng total arasaponins is beaten powder and crossed the 80-120 mesh sieve, feed intake by the prescription proportioning, elder generation in partial solvent, adds the thermosol thing stabilizing agent thermosol in the residual solvent that is preheating to 35-45 ℃ more lentamente, the limit edged stirs, and then various solids are added one by one, fully mix each back that adds, moistening fully to guarantee, cross colloid mill and pulverize back pelleting, drying, promptly.