CN102319394A - Xingnaojing composition for injection and preparation method thereof - Google Patents
Xingnaojing composition for injection and preparation method thereof Download PDFInfo
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Abstract
The invention provides a Xingnaojing composition for injection and a preparation method thereof; musk, radix curcumae, cape jasmine, and borneol are used as raw materials; component solubilization is realized by using self characteristics of the traditional Chinese medicine compounds through compound formulation; and thus a Xingnaojing composition for injection is prepared with reduced hidden danger and increased drug efficacy.
Description
Technical field
The present invention relates to a kind of Xing Nao Jing ' injection and use composition and method of making the same, the invention belongs to the category of field of pharmaceutical preparations.
Background technology
Cardiovascular and cerebrovascular disease is the No.1 killer of human health, and at present, China has 100,000,000 people to suffer from cardiovascular and cerebrovascular diseases such as hypertension, arteriosclerosis approximately.Along with China steps into aging society gradually; Cardiovascular and cerebrovascular disease is also increasing to China people's influence, and cerebrovascular disease especially comprises cerebral edema that acute cerebral hemorrhage, cerebral thrombosis and craniocerebral trauma cause, intracranial pressure rising, stupor etc.; Mortality rate is high; Seriously threatening patient's life,, be easy to cause death if can not get treating timely and effectively.
Injectable emulsion of the present invention is by motherland medical tradition name side---and representative side's " cow-bezoar bolus for resurrection " of waking up the patient from unconsciousness by clearing away heat prescription forms through subtracting flavor, with the Moschus refreshment of having one's ideas straightened out, is monarch drug in the side; The detoxifcation of ministerial drug Fructus Gardeniae clearing away heat-fire is with the fire of the bag that clears away heart-fire; Borneolum Syntheticum, Radix Curcumae repelling foulness with aromatics, sensible switching is to strengthen the have one's ideas straightened out effect of refreshment of Moschus.
Prescription prescription: Moschus 7.5g, Radix Curcumae 30g, Fructus Gardeniae 30g, the preparation of Borneolum Syntheticum 1g extracting solution: get Fructus Gardeniae, Radix Curcumae and add water 1500mL and distill, collect distillate 1000mL; Moschus is added in the above-mentioned distillate, and adding distil water 250mL distills, it is subsequent use to collect distillate 1000mL.
XINGNAOJING ZHUSHEYE has effects such as refreshment relieving convulsion, clearing away heat and cooling blood, promoting flow of QI and blood, detoxifcation pain relieving.Modern study shows that it has the effect of stronger stimulating central nervous system cell; Onset is rapid, and there is better curative effect the aspects such as stupor, tic, toxic encephalopthy and drug intoxication that cause for disturbance of consciousness, Heavy craniocerebral injury, cerebral hemorrhage, cerebral infarction, epidemic encephalitis type B, hepatic coma, nervous system infection.
Because the preparation technology of existing XINGNAOJING ZHUSHEYE mainly just adopts simple steam distillation to extract; The just lower boiling volatile material of collecting of part has caused extraction of active ingredients insufficient, does not especially collect water soluble ingredient in its technology; Caused having in the Fructus Gardeniae medical material loss fully of fine clearing away heat-fire, the active Fructus Gardeniae glycoside of removing pathogenic heat from blood and toxic substance from the body; Had a strong impact on curative effect, simultaneously owing in the preparation technology of former preparation, fully dissolve in order to make its volatility liposoluble constituent; In prescription, added a large amount of Tween 80s; As everyone knows, Tween 80 has very strong hemolytic, and therefore former XINGNAOJING ZHUSHEYE exists bigger side effect and potential safety hazard in therapeutic process.
For overcoming the defective of existing XINGNAOJING ZHUSHEYE; CN1562292A discloses a kind of XINGNAOJING injectable powder, and Fructus Gardeniae, Radix Curcumae, three kinds of compositions of Moschus are adopted certain density ethanol extraction separating treatment respectively, and adopts HP-that 3-methylcyclopentadecanol extract and Borneolum Syntheticum have been carried out enclose; But; Impurity level in the resultant extract of this method is more, and operating procedure is long, the industrialized great production difficulty.The Chinese patent document of CN1616020A discloses a kind of XINGNAOJING injectable powder; Adopt the method consistent to extract Aromatic water to Fructus Gardeniae, Radix Curcumae, Moschus, and then Aromatic water is carried out preparing XINGNAOJING powder pin behind the enclose with the HP-of fragrant water yield 5-30% with the medicine required standard.But because the fragrant water yield that obtains of this method is big, the enclose that again this Aromatic water is carried out HP-has increased the difficulty of big production operation, equally also is unfavorable for industrialized big production.
Summary of the invention
The object of the present invention is to provide a kind of Xing Nao Jing ' injection to use compositions.
Another object of the present invention is to provide a kind of Xing Nao Jing ' injection to use the preparation of compositions method.
Xing Nao Jing ' injection of the present invention is used compositions, is processed by following supplementary material:
Medicinal raw material:
Adjuvant:
Above-mentioned Xing Nao Jing ' injection is used compositions, it is characterized in that: process according to the method for being prepared as follows:
(1) leaching process: Fructus Gardeniae is extracted volatile oil with the petroleum ether percolation, and is subsequent use;
(2) Fructus Gardeniae of devolatilization hair oil is used ethanol extraction, extracting liquid filtering is concentrated into and crosses cation exchange resin behind the certain volume; With 5% hydrochloric acid solution as eluant; The gained eluent concentrates, after the D101 macroporous adsorbent resin, with 45% alcoholic solution as eluant; Gained eluent concentrating under reduced pressure gets the Fructus Gardeniae total saponins;
(3) get Moschus, Radix Curcumae, pulverize, place the mixed solvent of alcohol-water, add the Fructus Gardeniae total saponins, it is fully contacted, centrifugal, filter, after filtrating is reclaimed organic solvent, from water, separate out the volatile oil of Moschus and Radix Curcumae, subsequent use;
(4) get Borneolum Syntheticum, make its dissolving with lytic agent, subsequent use;
(5) mix above three kinds of subsequent use compositions, add normal saline; Phospholipid methoxy poly (ethylene glycol)-PHOSPHATIDYL ETHANOLAMINE and cholesterol are added soybean oil, the room temperature dissolving; With above two kinds of liquid mixing, the ultrasonic formation colostrum of popping one's head in places hermetic container; The decompression rotary evaporation is to forming colloidal state under the room temperature, and other gets glycine-HCl buffer solution, stabilizing agent, pH regulator agent adding hermetic container, continues reduction vaporization; Form even Emulsion, in joining filter chamber, the Emulsion that has prepared is delivered to nuclepore membrane filter with peristaltic pump; Carry out aseptic filtration, fill promptly gets.
Above-mentioned Xing Nao Jing ' injection is used the preparation of compositions method, it is characterized in that the method for said abundant contact is: percolation, merceration; Alcoholic acid volume ratio is 60%-90% in the mixed solvent.
Above-mentioned Xing Nao Jing ' injection is used the preparation of compositions method, it is characterized in that said pH regulator agent is sodium bicarbonate, sodium carbonate or sodium hydroxide.
Above-mentioned Xing Nao Jing ' injection is used the preparation of compositions method, it is characterized in that said stabilizing agent is glycerol, mannitol, xylitol or sorbitol.
Above-mentioned Xing Nao Jing ' injection is used the preparation of compositions method, and the lytic agent that it is characterized in that said Borneolum Syntheticum is one or more mixture with any mixed in the MCT Oil of Oleum Gossypii semen, safflower oil, fish oil, Oleum sesami, olive oil or C8～C14.
Above-mentioned Xing Nao Jing ' injection is used the preparation of compositions method, it is characterized in that: phospholipid is selected from a kind of in Ovum Gallus domesticus Flavus lecithin or the soybean phospholipid or they mixture with any mixed.
Above-mentioned Xing Nao Jing ' injection is used the preparation of compositions method, it is characterized in that Moschus is natural Moschus or artificial Moschus.
Above-mentioned Xing Nao Jing ' injection is used the preparation of compositions method, it is characterized in that may further comprise the steps:
(1) Fructus Gardeniae is extracted volatile oil with the petroleum ether percolation, and is subsequent use;
(2) Fructus Gardeniae of devolatilization hair oil is extracted 2 times under 65 ℃ of water-baths with 25 times of amount 75% ethanol, each 1.5h,, merge extractive liquid; Filter, and be concentrated into 100ml, add 1% aluminum sulfate, stir 2h at 70 ℃; Filter, filtrating is crossed cation exchange resin successively, with 5% hydrochloric acid solution as eluant; The D101 macroporous adsorbent resin, as eluant, the eluent concentrating under reduced pressure gets the Fructus Gardeniae total saponins with 45% alcoholic solution;
(3) get Moschus, Radix Curcumae, pulverize, place the mixed solvent of alcohol-water, add the Fructus Gardeniae total saponins, it is fully contacted, centrifugal, filter, after filtrating is reclaimed organic solvent, from water, separate out the volatile oil of Moschus and Radix Curcumae, subsequent use;
(4) get Borneolum Syntheticum, add the injection soybean oil and make dissolving, subsequent use;
(5) mix above three kinds of subsequent use compositions, add normal saline; Soybean phospholipid, methoxy poly (ethylene glycol)-PHOSPHATIDYL ETHANOLAMINE and cholesterol are added soybean oil, the room temperature dissolving; With above two kinds of liquid mixing, the ultrasonic formation colostrum of popping one's head in places hermetic container; The decompression rotary evaporation is to forming colloidal state under the room temperature, and other gets glycine-HCl buffer solution sodium bicarbonate and adds hermetic container, continues reduction vaporization 1 hour; Supersound process forms even Emulsion, in joining filter chamber; The Emulsion that has prepared is carried out aseptic filtration, and fill promptly gets.
The invention still further relates to a kind of Xing Nao Jing ' injection with the application of compositions on preparation treatment cardiovascular and cerebrovascular diseases medicament.
Inventive point of the present invention is:
Inventive point 1. compound compatibility solubilization methods
The present invention is not a solubilization method of indiscriminately imitating chemicals to the solubilising of slightly solubility composition in Moschus, the Radix Curcumae, as adds for example cosolvent, solubilizing agent such as tween 80; But utilize the characteristics of Chinese medicine compound self; Realize the composition solubilising through compound compatibility, need not to add separately adjuvant and, reduced the safety hidden danger of using adjuvant solubilising etc. to bring by special process or equipment; And have certain pharmacological action, more help the performance of drug effect.
Through the process of " get Moschus, Radix Curcumae, mixing is pulverized, and places the mixed solvent of alcohol-water; add the Fructus Gardeniae total saponins, it is fully contacted, and is centrifugal; filter, and behind the filtrating recovery organic solvent, from water, separates out the volatile oil of Moschus and Radix Curcumae; subsequent use ", thin layer chromatography detects and shows, contains the Fructus Gardeniae total saponins in Moschus of from water, separating out and the volatile oil of Radix Curcumae.
The present invention finds; Exist the material that the slightly solubility composition in Moschus, the Radix Curcumae is had solubilization in the Fructus Gardeniae---the Fructus Gardeniae total saponins; And the Fructus Gardeniae total saponins is positioned at the medicinal residues part of being abandoned by the XINGNAOJING traditional extraction technique; The antibacterial antioxidation of ability itself is removed free radical, strengthens the stability of volatile oil component.
Compound compatibility of the present invention is not that the Fructus Gardeniae total saponins is directly added in the slightly solubility composition of Moschus, Radix Curcumae; Belong to the triterpenes saponin compound and be based on the Fructus Gardeniae total saponins; Has the active ability of surface of good; Extract the slightly solubility composition in Moschus, the Radix Curcumae with it, the method for this compound compatibility is domestic and international initiative.
Patients such as stupor, tic, toxic encephalopthy are interior-heat caused by deficiency of YIN often, and the Fructus Gardeniae total saponins can play the effect of clearing away heat and cooling blood.As the Fructus Gardeniae total saponins of surfactant, can help other active component to break through blood brain barrier, thereby play the effect of guiding drug.Such compatibility has embodied the characteristics of Chinese medicine preparation.
The Fructus Gardeniae total saponins comes from Fructus Gardeniae volatile oil and extracts medicinal residues afterwards, has practiced thrift cost, and extraction process is simple, but also can be used for the production of other drug.
The aqueous extraction process of inventive point 2. " Moschus, Radix Curcumae " liposoluble constituent
The steam distillations that adopt when from Moschus, Radix Curcumae medical material, extracting liposoluble constituent in the prior art more, extraction time is long, and liposoluble constituent is heated and can loses, and uses the Petroleum ether extraction carbon dioxide supercritical fluid extraction, and cost is high.
Compound compatibility solubilization method of the present invention; Be exactly the aqueous extraction process of " Moschus, Radix Curcumae " liposoluble constituent in yet another aspect; The present invention is that surfactant reduces surface tension with the Fructus Gardeniae total saponins; Make " Moschus, Radix Curcumae " in the process of percolation, merceration, be prone to, thereby improve the usefulness that solvent infiltrates cell interior by the ethanol moistening of 60%-90%.Be effective ingredient diffusion then and be dissolved in the solvent, reach the purpose that improves extraction efficiency.The temperature of percolation, merceration can improve the stability of " Moschus, Radix Curcumae " liposoluble constituent well below the temperature of steam distillation.
Inventive point 3. " methoxy poly (ethylene glycol)-PHOSPHATIDYL ETHANOLAMINE " strengthens drug effect
The Fructus Gardeniae total saponins is an amphoteric surfactant; Also be contained among the liposoluble constituent of " Moschus, Radix Curcumae ", the present invention adopts the amphiphilic linear polymer---the methoxy poly (ethylene glycol) PHOSPHATIDYL ETHANOLAMINE, and uniform mixing is together to make Fructus Gardeniae total saponins and " volatile ingredient in Moschus, Radix Curcumae, the Fructus Gardeniae "; Promote micelle formation; Coordinate all medicines, make CD become an organic whole, break through blood brain barrier.
Borneolum Syntheticum is that the effect of messenger drug Borneolum Syntheticum mainly is a tying-in, the through sick institute of the efficacy of a drug of guiding " volatile ingredient in Moschus, Radix Curcumae, the Fructus Gardeniae ".The methoxy poly (ethylene glycol) PHOSPHATIDYL ETHANOLAMINE can be assisted the effect of Borneolum Syntheticum performance tying-in.
The invention has the advantages that: Xing Nao Jing ' injection prepared in accordance with the present invention is compared with compositions with former Xing Nao Jing ' injection with compositions, has the following advantages:
1. respect the compound compatibility rule, improve the utilization rate of medical material
The present invention utilize have fine clearing away heat-fire in its Fructus Gardeniae medical material, the active Fructus Gardeniae total saponins of removing pathogenic heat from blood and toxic substance from the body is as surfactant; Extract the liposoluble constituent in Moschus, the Radix Curcumae; This method is not only the method for distilling in a kind of modern times; That active component is extracted is more abundant, has more embodied the ingenious design that the present invention respects the compound compatibility rule.
2. determined curative effect, safety are good
The present invention has adopted emulsifying technology, more helps medicine and sees through blood brain barrier, act on rapidlyer, stablizes, and does not re-use the very strong Tween 80 of hemolytic in the prescription, and therefore, the safety of medication improves greatly.
Experiment shows; The present invention can directly see through blood brain barrier, alleviates cerebral edema, reduces intracranial pressure; Improve the cerebrospinal fluid PH; Significantly short wake up effect and good cerebral protection being arranged, and have anticoagulant, strengthen the histiocyte hypoxia-bearing capability and reach balance adjustment effect, obviously improving the clear-headed rate of comatose patient the central nervous system.
3. good stability
These article are studied through 24 months stability test, and the result shows that these article have good stability.
4. quality controllable
Adopt multiple Quality Control technology that the quality of preparation of the present invention is controlled, former relatively preparation has had significantly raising.
Adopt gas chromatography that the volatile ingredient of these article is carried out assay, the quality of strict control product has further strengthened the safety of medicine, the precision of this method, stability, good reproducibility, and sensitivity is high.
The specific embodiment
Embodiment 1: 1 of supplementary material consumption
A kind of Xing Nao Jing ' injection is used compositions, is processed by following supplementary material:
Medicinal raw material:
Adjuvant:
Embodiment 2: 2 of supplementary material consumption
A kind of Xing Nao Jing ' injection is used compositions, is processed by following supplementary material:
Medicinal raw material:
Adjuvant:
Embodiment 3: 3 of supplementary material consumption
A kind of Xing Nao Jing ' injection is used compositions, is processed by following supplementary material:
Medicinal raw material:
Adjuvant:
Embodiment 4: 1 of preparation process
Supplementary material consumption according to embodiment 1 prepares;
Fructus Gardeniae is extracted volatile oil with the petroleum ether percolation, and is subsequent use;
The Fructus Gardeniae of devolatilization hair oil is extracted 2 times under 65 ℃ of water-baths with 800ml75% ethanol, each 1.5h, merge extractive liquid, filters; And be concentrated into 100ml, and add 1% aluminum sulfate, stir 2h at 70 ℃, filter; Filtrating is crossed cation exchange resin successively, with 5% hydrochloric acid solution as eluant, the D101 macroporous adsorbent resin; As eluant, the eluent concentrating under reduced pressure gets Fructus Gardeniae total saponins 2.5g with 45% alcoholic solution;
Get Moschus and Radix Curcumae, pulverize, place 75% ethanol, add the Fructus Gardeniae total saponins, percolation, centrifugal, filter, after filtrating is reclaimed organic solvent, from water, separate out the volatile oil of Moschus and Radix Curcumae, subsequent use;
Get Borneolum Syntheticum, add the injection soybean oil and make dissolving, subsequent use;
Mix above three kinds of subsequent use compositions, add normal saline, soybean phospholipid, methoxy poly (ethylene glycol)-PHOSPHATIDYL ETHANOLAMINE and cholesterol are added soybean oil; The room temperature dissolving is after waiting to dissolve, with above two kinds of liquid mixing; The ultrasonic formation colostrum of popping one's head in places hermetic container, and the decompression rotary evaporation is to forming colloidal state under the room temperature; Other gets glycine-HCl buffer solution, sodium bicarbonate adds hermetic container, continues reduction vaporization 1 hour, forms even Emulsion; 10000 grades join in the filter chamber, use peristaltic pump to be delivered to oneself mounted aperture the Emulsion that has prepared and be the nuclepore membrane filter of 0.45 μ m and 0.22 μ m, carry out aseptic filtration; The filtrating of beginning is upright to be back in the original liquid box, treat that clarity test is qualified after, medicinal liquid receives with autoclaved serum bottle; After degerming finished, medicinal liquid moved into the fill chamber, and fill promptly gets.
Embodiment 5: 2 of preparation process
Supplementary material consumption according to embodiment 2 prepares, and just Moschus is replaced with the artificial Moschus; The preparation process is carried out according to embodiment 4.
Embodiment 6: 3 of preparation process
Supplementary material consumption according to embodiment 3 prepares, and just Moschus is replaced with the artificial Moschus; The preparation process is carried out according to embodiment 4.
Embodiment 7: Xing Nao Jing ' injection of the present invention is with short the wake up effect of compositions to mice
1, reagent and experimental animal
Experimental animal: healthy Kunming mouse, body weight 18-20g, male and female half and half.
Reagent: sodium chloride injection, Xing Nao Jing ' injection are with compositions (no Xishan standing grain), the medicine of the embodiment of the invention 1.
2, method and result
The mice random packet, tail vein injection sodium chloride injection Xing Nao Jing ' injection is with compositions (no Xishan standing grain), the medicine of the embodiment of the invention 1 respectively; Once a day, successive administration 3 days, 15min after the last administration; Lumbar injection pentobarbital sodium normal saline solution (3mg/ml) 0.3ml/20g, record mice righting reflex loss is calculated each class mean and standard deviation to the time of recovering; Carry out the t check, the result sees table 1.
Table 1 Xing Nao Jing ' injection with compositions to the free active influence of mice (n=10, x ± s)
Compare * P＜0.01 with the normal saline blank control group
Compare with matched group, the medicine of the embodiment of the invention 1 shows short effect of waking up.
Embodiment 8: Xing Nao Jing ' injection of the present invention pours into the influence of rat cerebral tissue's amino acid neurotransmitter again to GBI with compositions
Drugs of causing resuscitation by administering aromatic drugs has the central excitation effect, clinically disturbance of consciousness is had good refreshment effect.Modern study shows that excitatory amino acid EAA participates in the hypoxic ischemic damage of brain, in acute neuronal damage due to anoxia, the ischemia, plays key effect, and Hypoxia and ischemia hindbrain extracellular fluid EAA can obviously raise.
Injection fluid power of the present invention sees through blood brain barrier rapidly and directly acts on the central nervous system; Excitatory neurotransmitter Asp in the time of can reducing cerebral ischemia and rising inhibitory nerve mediator GABA Gly; Toxicity with the antagonism excitatory amino acid; Thereby the damage of the follow-up unit of going crazy of protection cerebral ischemia, antagonism ischemic cerebral lesion, the effect that also has convulsion and cerebral edema.
Animal divides into groups and medication
The SD rat, male and female are regardless of, body weight 200～280g; Be divided into sham operated rats, model group, embodiment 2 groups of (1mg/mld is by the crude drug amount), normal saline blank control group, Xing Nao Jing ' injection at random with compositions group (no Xishan standing grain, 2mg/mld; By the crude drug amount), totally 5 groups, 10 every group.Each is organized the rat dosage and calculates by the body surface area formula, sham operated rats and model group injecting normal saline 1ml/kgd, and each group administration after modeling behind the successive administration 60min, undergos surgery.
The model method for preparing
Adopt the pulsinellide method; Dosage by 3ml/kg gives the capable intraperitoneal anesthesia of rat 10% chloral hydrate, and anesthesia back rat is prostrate on operating-table, first, second cervical vertebra upper cut behind neck; Separating muscle; Expose atlas two flank apertures, electricity consumption is coagulated the pen burning and is closed the bilateral vertebral artery, causes permanent closing; Put rat in dorsal position, separate bilateral common carotid arteries, close bilateral common carotid arteries 45min with arteriole folder folder, open bulldog clamp pours into 6h, then sacrificed by decapitation again.Sham operated rats is separated vertebral artery and common carotid artery, and not all right vertebral artery closes with fixed attention with the common carotid artery folder and closes, and surplus operation process is identical.
The preparation of BIAO and BEN
Animal is in perfusion back sacrificed by decapitation again, and rat brain is got in operation, place rapidly get on the ice pan right side brain from antinion to occipital lobe be divided into 4,7, G, I five equilibrium; Get G, I brain sheet rapidly, after accurately weighing, add the homogenate of 1ml methanol by every 50mg tissue; 2000g; 4 ℃ centrifugal 30 minutes, collect supernatant residue reuse methanol and extract twice with method, merges the supernatant of 3 extractions.Extracting solution is put and is boiled off methanol on the boiling water bath, in the residue of remainder, accurately adds 80% ethanol 5ml, ultrasonic Treatment 30min, 2000g, 4 ℃ centrifugal 30 minutes, collect supernatant and be used to detect the cerebral tissue amino acid neurotransmitter.
Statistical analysis
Each is organized numerical value and representes that with x ± s relatively adopt the spss10.0 software kit to carry out monofactorial variance analysis between group, significance level is got α=0.05 or 0.01.
Result of the test
The ischemia 45min of rat cerebral tissue, pour into 6h again after, model group Glu, Asp content significantly raise (P＜0.01) than sham operated rats, 2 groups of embodiment significantly are lower than model group (P＜0.01) with injection group Asp content amount.
2 groups of embodiment and injection group GABA, Gly content are significantly higher than model group (P＜0.01), and wherein embodiment is superior to the injection group for 2 groups.
Therefore; The medicine of the embodiment of the invention 2 can be through reducing Glu, the Asp in the ischemic region cerebral tissue; Improve the toxicity of the content of GABA Gly with the antagonism excitatory amino acid, thus the damage of the follow-up unit of going crazy of protection cerebral ischemia, and also effect is better than Xing Nao Jing ' injection and uses the compositions group; Good like this effect, its reason possibly be come from have clearing away heat-fire, the active Fructus Gardeniae total saponins of removing pathogenic heat from blood and toxic substance from the body.
Table 2 is respectively organized the content μ mol/g (x ± s) of cerebral tissue amino acid neurotransmitter
| Group | Glu | Asp | GABA | Gly |
| Sham operated rats | 3.80±0.75 | 3.65±0.96 | 10.77±2.43 | 2.72±0.49 |
| Model group | 5.78±0.97* | 5.99±0.89* | 11.12±3.19 | 3.81±0.57 |
| Xing Nao Jing ' injection is used the compositions group | 4.82±0.89* | 4.90±0.75* | 14.23±2.52* | 4.20±0.78* |
| The medicine of the embodiment of the invention 2 | 4.26±0.75* | 4.15±0.58* | 18.99±3.75 | 4.81±0.68* |
Annotate: compare * P＜0.01 with sham operated rats
Embodiment 9: Xing Nao Jing ' injection of the present invention is with the influence of compositions to rat cerebral ischemia cerebral tissue moisture content
Animal divides into groups and medication, and the model method for preparing is with embodiment 9.
The preparation animal of BIAO and BEN is in pour into the back sacrificed by decapitation again, and rat brain is got in operation, places rapidly and gets brain on the ice pan, and with the residual blood of normal saline flushing tissue surface, filter paper carefully blots surface moisture, removes olfactory bulb, brain stem, XIAONAO.Be loaded in the weighing botle that precision weighing crosses, accurate weighing weight in wet base of electronic balance and record take out after going into 105 ℃ of oven dry of baking oven 48h, and through weighing repeatedly after constant weight (claim every day once, until twice weight change less than 1%), dry weight is organized in the record conduct.Try to achieve moisture content with dried weight in wet base method.Formula is following:
Cerebral tissue moisture content (%)=(weight in wet base-dry weight)/weight in wet base * 100%
Experimental result sees the following form 3.
Experimental result shows, compares with sham operated rats, and model group cerebral tissue moisture content obviously increases (* P＜0.01).Compare with model group, the rat degree of cerebral edema that the embodiment of the invention is 2 groups decreases.
Table 3 Xing Nao Jing ' injection is with the influence of compositions to rat cerebral ischemia cerebral tissue moisture content
| Group | Dosage | Cerebral tissue moisture content (%) |
| Sham operated rats | The equal-volume distilled water | 76.32±1.63 |
| Model group | The equal-volume distilled water | 81.73±0.98* |
| Xing Nao Jing ' injection is used the compositions group | 2mg/ml | 79.22±1.10* |
| The medicine of the embodiment of the invention 2 | 1mg/ml | 78.07±0.92* |
Annotate: compare * P＜0.01 with sham operated rats
Embodiment 10: Xing Nao Jing ' injection of the present invention is with the zest and the hemolytic of compositions
Get the medicine (1mg/ml by crude drug amount) of Xing Nao Jing ' injection, give mice intramuscular injection 1ml respectively,, observe zest and hemolytic through 1,5,24,72 hour and 5-7 days with compositions (tween 80 concentration is 1%), the embodiment of the invention 2.
Experimental result shows: the medicine nonirritant of the embodiment of the invention 2, mouse red blood cell does not have haemolysis.Fructus Gardeniae total saponins among the present invention is safe.
Claims (10)
1. an Xing Nao Jing ' injection is used compositions, it is characterized in that: processed by following supplementary material:
Medicinal raw material:
Adjuvant:
2. Xing Nao Jing ' injection according to claim 1 is used compositions, it is characterized in that: process according to the method for being prepared as follows:
(1) Fructus Gardeniae is extracted volatile oil with the petroleum ether percolation, and is subsequent use;
(2) Fructus Gardeniae of devolatilization hair oil is used ethanol extraction, extracting liquid filtering is concentrated into and crosses cation exchange resin behind the certain volume; With 5% hydrochloric acid solution as eluant; The gained eluent concentrates, after the D101 macroporous adsorbent resin, with 45% alcoholic solution as eluant; Gained eluent concentrating under reduced pressure gets the Fructus Gardeniae total saponins;
(3) get Moschus, Radix Curcumae, pulverize, place the mixed solvent of alcohol-water, add the Fructus Gardeniae total saponins, it is fully contacted, centrifugal, filter, after filtrating is reclaimed organic solvent, from water, separate out the volatile oil of Moschus and Radix Curcumae, subsequent use;
(4) get Borneolum Syntheticum, make its dissolving with lytic agent, subsequent use;
(5) mix above three kinds of subsequent use compositions, add normal saline; Phospholipid methoxy poly (ethylene glycol)-PHOSPHATIDYL ETHANOLAMINE and cholesterol are added soybean oil, the room temperature dissolving; With above two kinds of liquid mixing, the ultrasonic formation colostrum of popping one's head in places hermetic container; The decompression rotary evaporation is to forming colloidal state under the room temperature, and other gets glycine-HCl buffer solution stabilizing agent, the pH regulator agent adds hermetic container, continues reduction vaporization; Form even Emulsion, in joining filter chamber, the Emulsion that has prepared is delivered to nuclepore membrane filter with peristaltic pump; Carry out aseptic filtration, fill promptly gets.
3. each described Xing Nao Jing ' injection of claim 1-2 is used the preparation of compositions method, it is characterized in that the method for said abundant contact is: percolation, merceration; Alcoholic acid volume ratio is 60%-90% in the mixed solvent.
4. Xing Nao Jing ' injection according to claim 3 is used the preparation of compositions method, it is characterized in that said pH regulator agent is sodium bicarbonate, sodium carbonate or sodium hydroxide.
5. use the preparation of compositions method according to claim 3 a described Xing Nao Jing ' injection, it is characterized in that said stabilizing agent is glycerol, mannitol, xylitol or sorbitol.
6. Xing Nao Jing ' injection according to claim 3 is used the preparation of compositions method, and the lytic agent that it is characterized in that said Borneolum Syntheticum is one or more mixture with any mixed in the MCT Oil of Oleum Gossypii semen, safflower oil, fish oil, Oleum sesami, olive oil or C8～C14.
7. Xing Nao Jing ' injection according to claim 3 is used the preparation of compositions method, it is characterized in that: phospholipid is selected from a kind of in Ovum Gallus domesticus Flavus lecithin or the soybean phospholipid or they mixture with any mixed.
8. Xing Nao Jing ' injection according to claim 3 is used the preparation of compositions method, it is characterized in that Moschus is natural Moschus or artificial Moschus.
9. Xing Nao Jing ' injection according to claim 1 is used the preparation of compositions method, it is characterized in that:
(1) Fructus Gardeniae is extracted volatile oil with the petroleum ether percolation, and is subsequent use;
(2) Fructus Gardeniae of devolatilization hair oil is extracted 2 times under 65 ℃ of water-baths with 25 times of amount 75% ethanol, each 1.5h,, merge extractive liquid; Filter, and be concentrated into 100ml, add 1% aluminum sulfate, stir 2h at 70 ℃; Filter, filtrating is crossed cation exchange resin successively, with 5% hydrochloric acid solution as eluant; The D101 macroporous adsorbent resin, as eluant, the eluent concentrating under reduced pressure gets the Fructus Gardeniae total saponins with 45% alcoholic solution;
(3) get Moschus, Radix Curcumae, pulverize, place the mixed solvent of alcohol-water, add the Fructus Gardeniae total saponins, it is fully contacted, centrifugal, filter, after filtrating is reclaimed organic solvent, from water, separate out the volatile oil of Moschus and Radix Curcumae, subsequent use;
(4) get Borneolum Syntheticum, add the injection soybean oil and make dissolving, subsequent use;
(5) mix above three kinds of subsequent use compositions, add normal saline; Soybean phospholipid methoxy poly (ethylene glycol)-PHOSPHATIDYL ETHANOLAMINE and cholesterol are added soybean oil, the room temperature dissolving; With above two kinds of liquid mixing, the ultrasonic formation colostrum of popping one's head in places hermetic container; The decompression rotary evaporation is to forming colloidal state under the room temperature, and other gets glycine-HCl buffer solution sodium bicarbonate and adds hermetic container, continues reduction vaporization 1 hour; Supersound process forms even Emulsion, in joining filter chamber; The Emulsion that has prepared is carried out aseptic filtration, and fill promptly gets.
10. claim 1 or 2 described Xing Nao Jing ' injections are with the application of compositions on preparation treatment cardiovascular and cerebrovascular diseases medicament.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103816118A (en) * | 2014-02-14 | 2014-05-28 | 西藏海思科药业集团股份有限公司 | Polyene phosphatidyl choline composition for injection and preparation method thereof |
| CN108821956A (en) * | 2018-05-25 | 2018-11-16 | 无锡济民可信山禾药业股份有限公司 | A method of it distills to extract from XINGNAOJING ZHUSHEYE and recycles curcumin in waste residue |
| CN108929350A (en) * | 2018-05-25 | 2018-12-04 | 无锡济民可信山禾药业股份有限公司 | A method of it distills to extract from XINGNAOJING ZHUSHEYE and recycles Gardenoside in waste liquid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1279892C (en) * | 2004-08-23 | 2006-10-18 | 江苏正大天晴药业股份有限公司 | Fat emulsion injection of 'Xingnaojing' and its preparing process |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1279892C (en) * | 2004-08-23 | 2006-10-18 | 江苏正大天晴药业股份有限公司 | Fat emulsion injection of 'Xingnaojing' and its preparing process |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103816118A (en) * | 2014-02-14 | 2014-05-28 | 西藏海思科药业集团股份有限公司 | Polyene phosphatidyl choline composition for injection and preparation method thereof |
| CN108821956A (en) * | 2018-05-25 | 2018-11-16 | 无锡济民可信山禾药业股份有限公司 | A method of it distills to extract from XINGNAOJING ZHUSHEYE and recycles curcumin in waste residue |
| CN108929350A (en) * | 2018-05-25 | 2018-12-04 | 无锡济民可信山禾药业股份有限公司 | A method of it distills to extract from XINGNAOJING ZHUSHEYE and recycles Gardenoside in waste liquid |
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