CN102743373A - Application of Casticin in medicine preparation for analgesia - Google Patents
Application of Casticin in medicine preparation for analgesia Download PDFInfo
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Abstract
The invention relates to the medicine technical field, and relates to a novel application of Casticin in medicine preparation for analgesia. The animal experiments prove that Casticin possesses obvious analgesic effect, thereby Casticin can be used for preparing the medicines capable of treating pain symptoms. The invention provides a medicine resource for preparing the novel analgesic medicine.
Description
Technical field
The present invention relates to medical technical field, is the new purposes that casticin is used to prepare analgesic.
Background technology
Pain is a symptom of multiple disease, and it makes the patient experience painful, and especially severe pain possibly cause that also physiological function is disorderly, even shock.Therefore, suitably the drug application alleviating pain prevents that issuable physiological function disorder from being very necessary.Lenitive medicine by its pharmacological mechanism, can be divided into two big types: a kind of is mainly to act on the central nervous system, can optionally eliminate or lenitive medicine.In the analgesia process, patient's Consciousness, other feel unaffected, this type medicine is called analgesic (analgesics).Another kind is the medicine with analgesia, analgesic and antiinflammatory action, and is effective to various dull pains (like headache, toothache etc.).Typical analgesic is opium alkaloid class and synthetic substitute thereof, is characterized in that analgesic activity is powerful, is easy to addiction but use repeatedly, so be called addicted analgesics or narcosis analgesic again.
Casticin (Casticin-5,3 '-dihydroxy-3,6,7,4 '-tetramethoxyflavon, be the flavones ingredient in many Chinese crude drugs in the Vitex PAME), be the flavone component in the Chinese crude drug Fructus Viticis.Its chemical structural formula is following:
The Pharmacopoeia of the People's Republic of China therefore can be with its important indicator property composition as medical material and crude drug quality evaluation with the discriminating composition of casticin as the Fructus Viticis crude drug.
Casticin mainly is present in the Verenaceae Vitex various plants like wild pepper (Vitex trifolia L), Vitex rotundifolia (Vitex trifolia L.var.simplicifolia Cham), five-leaved chaste tree (Vitex negundo L), Herba Viticis Cannabifoliae (Vitex negundo var.cannabifolia (Sieb.et Zucc.) Hand.-Mazz.) etc.And the Fructus Viticis that pharmacopeia is recorded is the dry fruit of Verenaceae plant Vitex rotundifolia (Vitex trifolia var simplicifolia Cham.) or wild pepper (V.trifolia L.); Effect with wind-dispelling heat-dissipating, clear sharp head, successive dynasties book on Chinese herbal medicine ancient books and records are all on the books.
Research shows that the wild pepper plant mainly contains compositions such as volatile oil, flavonoid (aglycon and glycosides), iridoid (aglycon and glycosides), diterpene (aglycon and glycosides), alkaloid, steroidal.Wherein casticin can be blocked by the spontaneity of the inductive male guinea pig trachea of histamine and shrink as its main component, through stabilizing cell membrane, thereby suppresses the release in the histamine release from mast cells; Find in the experiment in vitro that casticin can optionally suppress the hypertrophy of mouse T lymphocyte, can suppress the growth of tumor cell line, also have the lymphopoietic activity of inhibition, lymphocytoma is had treatment potentiality (Gemini; A., Subagus, W.; Ibnu, G.G., Lukman; H., Timmerman, H.; Rob Verpoorte., 2002.Tracheospasmolytic activity of Viteosin-A and Vitexcarpin isolated from Vitex trifolia.Planta Med.68,1047-1049).Casticin can block through impelling the cancerous cell generation G2/M phase, and finally induces its apoptosis to bring into play active anticancer (Kobayakawa, the J. of anticancer propagation; Sato-Nishimori, F., Moriyasu; M.; Matsukawa, Y., 2004.G2-M arrest and antimitotic activity mediated by Casticin; A flavonoid isolated from Viticis fructus (Vitex rotundifolia linne fil.) .Cancer Lett.208,59-64.).The HeLa Cells proliferation activity there is stronger inhibitory action, is dosage and time dependence; This inhibitory action and reduction CyclinB1 protein expression, activation P21 albumen relevant (Xie Jing, the White Army, Sheng Xifeng; Cao Jianguo; Xie Wanyu. the research of casticin vitro inhibition HeLa Cells propagation. Chinese cancer magazine, 2010,20 (6): 406-410).Casticin also has stronger antiinflammatory action, and rat paw edema and the increase of acetic acid induced mice capillary permeability all have obvious suppression effect (Lin S, Zhang H due to the corridor swelling of xylol induced mice ear, the Ovum Gallus domesticus album; Han T; Wu JZ, Rahman K, Qin LP.In vivo effect of casticin on acute inflam mation.Journal of Chinese Integrative Medicine; 2007,5 (5) 1:573-576).But do not see so far casticin have analgesic activities relevant report.
Summary of the invention
The present invention is that casticin (PAME) provides a kind of new purposes of treating pain symptom.
Casticin method for preparing of the present invention is following:
1, preparation casticin extracting solution
The PAME crude drug is used 75% alcohol reflux by routine, get the casticin extracting solution;
2, preparation extractum
With said extracted liquid concentrating under reduced pressure, get extractum;
2, extraction
2.1 the preparation of extract extractum suspension
The extractum deionized water is disperseed, get extract extractum suspension;
2.2 petroleum ether extraction
With the ether extraction of above-mentioned suspension PetroChina Company Limited., petroleum ether extraction liquid;
2.3 dichloromethane extraction
In petroleum ether extraction liquid, add dichloromethane extraction and get dichloromethane extraction liquid;
2.4 concentrate
Above-mentioned dichloromethane extraction liquid is evaporated to is the extractum shape, obtain Fructus Viticis dichloromethane extraction position;
3, purification
With above-mentioned dichloromethane position with 95% medical alcohol heating for dissolving after, put and be chilled to room temperature, 0.45 μ m membrane filtration; Filtrating slowly joins (Sephadex LH-20 in the sephadex chromatography post of having handled well; Φ 40 * 600mm), 95% medical alcohol eluting, flow velocity 1BV/h; Collect the 3-8BV eluent; With TLC and HPLC inspection, the result finds that casticin concentrates on the 5-6BV eluent, and is eluted with a kind of green pigment respectively.Merge the 5-6BV eluent, concentrating under reduced pressure obtains the yellow green powder, with a small amount of 95% medical alcohol drip washing, drains, and 60 ℃ of drying under reduced pressure 24h get the casticin yellow powder to constant weight.
Through animal experiment, find that casticin has significant analgesia role, thereby can be used for preparing the medicine of treating pain symptom.
The present invention provides a kind of medicament sources for the new analgesic of preparation.
The specific embodiment
The preparation of embodiment 1. casticins
1, PAME medical material 75% ethanol extract concentrates
Get the PAME crude drug (lot number: 20081003) 100.5 grams, put in the 2000ml round-bottomed flask, according to the extraction process requirement, add 75% ethanol 1200ml, reflux, extract, 2h is put coldly, filters; Filtering residue continues to add 75% ethanol 1000ml, and reflux, extract, 2h is put coldly, filters; Twice filtrating merges, and as herbal extract, is total to 2100ml.Said extracted liquid is put in the 1000ml round-bottomed flask, the gradation concentrating under reduced pressure, and when cumulative volume was concentrated into 100ml, concentrated solution was the extractum shape, put that to be chilled to room temperature for use.
2, extraction
2.1 the dispersion of extract
In above-mentioned extractum, add the 200ml deionized water, stir, heat leaves standstill a little, puts and is chilled to room temperature, and the layer that anhydrates inclines; Continue with 200ml * 2 time washing, the layer that anhydrates inclines; At last, add the 200ml deionized water and disperse extract extractum;
2.2 petroleum ether extraction
In the above-mentioned extractum suspension, contain partial pigment, we take the method for petroleum ether extraction, remove partial pigment and part low-polarity component.In above-mentioned suspension, add the 200ml petroleum ether, jolting, standing demix is obtained petroleum ether layer, and TLC follows the tracks of, and water layer continues with the 200ml petroleum ether extraction; Through the TLC tracking verification, behind petroleum ether extraction four times, the petroleum ether extraction layer has not had obvious composition, so confirm extract petroleum ether extraction four times, each 200ml, i.e. petroleum ether: water layer=extract four time at 1: 1.
2.3 dichloromethane extraction
In above-mentioned petroleum ether extraction liquid, add the 200ml dichloromethane, jolting, standing demix is obtained dichloromethane layer, and TLC follows the tracks of, and water layer continues with the 200ml dichloromethane extraction; Through the TLC tracking verification, behind dichloromethane extraction four times, water layer has not had tangible flavones ingredient, so confirm extract dichloromethane extraction four times, each 200ml, i.e. dichloromethane: water layer=extract four time at 1: 1.Discard water layer, combined dichloromethane extract, 690ml altogether.
Concentrating of dichloromethane extraction liquid
Above-mentioned dichloromethane extraction liquid is put in the 1000ml round-bottomed flask, the gradation concentrating under reduced pressure, and when cumulative volume was concentrated into 100ml, concentrated solution was the extractum shape, obtained Fructus Viticis dichloromethane extraction position 3.5g, put that to be chilled to room temperature for use.
3, purification
Above-mentioned dichloromethane position 3.5g slowly adds 95% medical alcohol, and heating edge dissolving in limit is to just all dissolvings, shared solvent 18ml.Put and be chilled to room temperature, 0.45 μ m membrane filtration; Filtrating slowly joins (Sephadex LH-20 in the sephadex chromatography post of having handled well; Φ 40 * 600mm), 95% medical alcohol eluting, flow velocity 1BV/h; Collect the 3-8BV eluent; With TLC and HPLC inspection, the result finds that casticin concentrates on the 5-6BV eluent, and is eluted with a kind of green pigment respectively.Merge the 5-6BV eluent, concentrating under reduced pressure obtains the yellow green powder, with a small amount of 95% medical alcohol drip washing, drains, and 60 ℃ of drying under reduced pressure 24h obtain yellow powder to constant weight.
With method for preparing 3 lot sample article, be that index is investigated the purity and the rate of transform with the casticin.The result shows that the casticin average purity is 91.22%, and the mean transferred rate of casticin in purge process is 80.57%.According to " medicine registration management way " (trying), the Chinese medicine effective monomer component is registered as new drug, and its effective ingredient total content must surpass 90%, so the prepared dry of method for preparing of the present invention is casticin, meets the new drug requirements of customs declaration.
Embodiment 2. casticin analgesic test
(1) chemical substance irritant test
1, experiment material
(1) medicine
PAME: by embodiment 1 preparation, it is subsequent use to be mixed with 0.2%, 0.4%, 0.8% medicinal liquid respectively with the distilled water that contains 0.5%CMC during experiment.
Medicine and reagent: formaldehyde (analytical pure), acetic acid (analytical pure) [Shanghai traditional Chinese medicines group chemical reagent responsibility company limited]; Morphine, Allylnoroxymorphone, methylene blue (buying on behalf) by the religion Bao Chu of The 2nd Army Medical College; Aspirin sodium, tramadol, pentobarbital sodium (Beijing Sihuan Pharmaceutical Co., Ltd).The Configuration Values respective concentration is subsequent use during experiment.
(2) animal
The ICR mice, body weight 20～22g, laboratory animal production licence number: SCXK (Shanghai) 2007003.Provide by Second Military Medical University, PLA Animal Experimental Study center.The quarantine back is subsequent use.
2, experimental technique
(1) writhing test
Get 50 of Kunming mouses, male and female half and half are divided into model control group (N=10), positive controls (N=10), PAME high dose group (N=10), middle dose groups (N=10), low dose group (N=10) at random.Irritate stomach distilled water, 2% aspirin medicinal liquid, 0.8%, 0.4%, 0.2%PAME pill liquid 10ml/kg respectively by group, 1 hour pneumoretroperitoneum of administration is injected 0.6% acetic acid 10ml/kg, writes down in 15 minutes and turns round the body number of times.2～3min behind the injection acetum, behavior reactions such as abdominal part indent, trunk and hind leg extension, buttocks stilt appear in mice, are called writhing response (writhing response), and the interior frequency of occurrences of 15min was the highest after this was reflected at lumbar injection.Experimental data is handled with the SPSS11.0 statistical software.Relatively adopt one factor analysis of variance between each group, wherein the neat person of variance uses the LSD method, and the heterogeneity of variance person uses the check of Dunnett ' st3 method.
(2) gate-Papacostas' tests
40min before giving mice vola subcutaneous injection formalin solution gives the mice administration of fasting 15h with basic, normal, high dosage-20mg/kg, 40mg/kg, the 80mg/kg of Compound P AME with the mode of irritating stomach.Behind the 40min; Using range is the formalin solution 20 μ l of microsyringe every the right vola of mice subcutaneous injection 5% in receiving the examination group of 50 μ l; Insert one immediately and be suspended on that volume is in the large beaker of 2000ml on the iron stand; The mirror of 30 ° of inclinations is placed in the container below, observes the right vola reaction of mice to subcutaneous injection 5% formalin solution from minute surface.Positive control drug morphine (10mg/kgs.c.) 30min subcutaneous injection administration before giving the right vola of mice subcutaneous injection formalin solution.
The phase when reaction that causes behind the subcutaneous injection formalin solution of mice vola can be divided into two: 0～10min person of appearance is that the reaction that I phase (early stage phase), 10～60min occur is II phase (a tardy phase).The I phase reaction mainly is directly to stimulate due to the c fiber, and II should have inflammatory mechanism to participate on the contrary.Pain reaction obviously reduces after injecting 5% formalin solution, 90～120min.We with 0～5min be set at I phase (early stage phase), 15～25min is set at II phase (tardy phase); In two time periods, observe mice and lick, shake is injected the persistent period length of foot as the pain index.Do between group the t check relatively each administration group and blank control group I mutually with II mutually in mice lick, shake quilt and inject the sufficient persistent period and whether have significant difference.
(3) mice capsaicin test
25min before giving mice vola subcutaneous injection capsaicin solution gives the mice administration of fasting 15h with the basic, normal, high dosage 20mg/kg of PAME, 40mg/kg, 80mg/kg with the mode of lumbar injection.Behind the 25min; Using range is microsyringe every right vola subcutaneous injection capsaicin solution (1.6 μ g of mice in receiving the examination group of 50 μ l; 20 μ l); Insert one immediately and be suspended on that volume is in the large beaker of 2000ml on the iron stand, the mirror of 30 degree that tilt is placed in the container below, observes the reaction of mice to the right vola of subcutaneous injection capsaicin solution from minute surface.Positive control drug morphine (10mg/kg s.c.) 30min subcutaneous injection administration before giving the right vola of mice subcutaneous injection capsaicin solution.
Behind the subcutaneous injection capsaicin solution of mice vola, the pain reaction of initiation is the inflammatory pain reaction that has peripheral neurons to participate in.Pain reaction obviously reduces behind injection capsaicin solution 8～10min.We are set at 0～5min and observe the period; During this period of time observe mice and lick, shake is injected the persistent period length of foot as the pain index.Do between group the t check relatively each administration group lick with blank control group mice in 0～5min, whether shake is existed significant difference by the sufficient persistent period of injection.
3, experimental result
(1) the Dichlorodiphenyl Acetate induced mice is turned round the influence of body
After the model group mice gave 0.6% acetic acid, pain symptom was obvious, and it is many to turn round body action.Compound P AME20mg/kg, 40mg/kg, three dosage of 80mg/kg have significant inhibitory effect to the mouse writhing number of times that lumbar injection acetic acid causes, and are certain dose-effect relationship.ED (50) is 39.07mg/kg.The acetic acid twisting experimental result of blank control group, positive control drug group, basic, normal, high five dose groups of PAME is seen table 1.
Table 1PAME Dichlorodiphenyl Acetate induced mice is turned round the influence (mean ± SEM) of body number of times
Annotate: compare * * P＜0.01 with model group.
(2) to the influence of formalin induced mice pain
In the experiment of mice formalin; Compare with model control group; Compound P AME20mg/kg, 40mg/kg, three dosage of 80mg/kg lick with the mice that II is caused in mutually at I vola subcutaneous injection 5% formalin solution mutually; Shake is had significant inhibitory effect by the persistent period of injection foot, and is certain dose-effect relationship; The inhibition effect of the similar narcosis analgesic morphine of the effect of inhibition of pain.The mice formalin experimental result of blank control group, positive control drug group, the basic, normal, high dose groups of Compound P AME is seen table 2.
Table 2PAME is to the influence of formalin induced mice pain (mean ± SEM)
Annotate: compare * P＜0.05, * * P＜0.01 with model group.
(3) influence pain caused to the mice capsaicin
In the experiment of mice capsaicin; Compare with model control group; PAME20mg/kg, 40mg/kg, three dosage of 80mg/kg are to vola subcutaneous injection capsaicin solution (1.6 μ g; 20 μ l) mice that in 0～5min, is caused licked and shakes by the persistent period of injection foot has significant inhibitory effect, and is certain dose-effect relationship.The mice capsaicin experimental result of blank control group, positive control drug group, the basic, normal, high dose groups of PAME sees table 3 for details.
Table 3PAME licks, trembles the influence (mean ± SEM) of foot time to the capsaicin induced mice
Annotate: compare * * P＜0.01 with model group.
4, conclusion
The acetic acid twisting test shows that PAME has significantly suppressed acetic acid stimulates the mouse writhing number of times that causes.The formalin irritant test shows that PAME obviously suppresses mice I and licks the sufficient time mutually with II mutually, with model group significant difference is arranged relatively, and is dose dependent.The capsaicin irritant test shows that PAME has reduced mice very significantly and licked the sufficient time.Above result of the test prompting, PAME stimulates the pain that causes to have the obvious suppression effect to chemical substance.
(2) thermostimulation pain test
1, experiment material
(1) medicine
PAME: receive the reagent thing, pale yellow powder, purity 91.31% is provided by pharmacognosy teaching and research room of Cellege of Pharmacy, No. 2 Military Medical Univ., PLA.Test lot number: 20090501.It is subsequent use to be mixed with 0.2%, 0.4%, 0.8% medicinal liquid respectively with the distilled water that contains 0.5%CMC during experiment.
Medicine and reagent: formaldehyde (analytical pure), acetic acid (analytical pure) [Shanghai traditional Chinese medicines group chemical reagent responsibility company limited]; Morphine, Allylnoroxymorphone, methylene blue (buying on behalf) by the religion Bao Chu of The 2nd Army Medical College; Aspirin sodium, tramadol, pentobarbital sodium (Beijing Sihuan Pharmaceutical Co., Ltd).The Configuration Values respective concentration is subsequent use during experiment.
(2) animal
The ICR mice, body weight 20～22g, laboratory animal production licence number: SCXK (Shanghai)-2007-003.Provide by Second Military Medical University, PLA Animal Experimental Study center.The quarantine back is subsequent use.
2, experimental technique
(1) hot plate test
Select for use the female ICR mice of 18～22g to carry out the experiment of mice hot plate.Mice is positioned over 55 ± 1 ℃ intelligent hot-plate instrument (model: YLS-6B intelligence hot-plate instrument; The place of production: Huaibei Zhenghua Biological Instrument Co., Ltd.), write down its vola contact hot plate to the time that occurs licking metapedes, playing metapedes or jump, promptly the hot plate response latency is as threshold of pain index.At first measure the basic threshold of pain of respectively organizing mice, normal value should be at 5～30s, and reject less than 5s or greater than 30s person the threshold of pain; Every mice is every at a distance from 1 basic pain threshold of 20min survey, and the average pain threshold of getting 3 mensuration numerical value is as the basic threshold of pain.Standard compliant mice, random packet.Standard compliant mice is carried out 40min before the hot plate experiment, give the mice administration of fasting 15h with the mode of irritating stomach basic, normal, high five dosage-20mg/kg, 40mg/kg, the 80mg/kg of PAME.(10mg/kg s.c.) carries out the subcutaneous injection administration as positive control drug 30min before the experiment beginning to mice to morphine.For preventing that foot from scalding, this experiment deadline is 60s, and mice reaches that 60s person stops to test incubation period and in 60s after the medication.And the analgesic effect of in 120min, observing Compound P AME continuously.
(2) mice hot water tail-flick test (The tail-immersion test)
Select for use 18～22g ICR mice to carry out the experiment of mice hot water whipping.Thermostat water bath (model: DKS-11 digital display water-bath with 54 ± 1 ℃ of mouse tail lower vertical immersions; The place of production: blue sky, Hangzhou assay apparatus factory), immersion length is 3.5cm; The record mouse tail bounces back out incubation period of the water surface as surveying the pain index.At first measure the basic threshold of pain of respectively organizing mice, normal value should be at 0～3s, and reject greater than 3s person the threshold of pain; Every mice is every at a distance from 1 basic pain threshold of 15min survey, and the average pain threshold of getting 3 mensuration numerical value is as the basic threshold of pain.Standard compliant mice, random packet.Standard compliant mice is carried out the preceding 40min of hot water whipping experiment, give the mice administration of fasting 15h with the mode of irritating stomach basic, normal, high five dosage of PAME.(10mg/kg s.c.) carries out the subcutaneous injection administration as positive control drug 30min before the experiment beginning to mice to morphine.For preventing that afterbody from scalding, this experiment deadline is 7s, and mice reaches that 7s person stops to test incubation period and in 7s after the medication; And the analgesic effect of in 120min, observing Compound P AME continuously.
The mouse tail end is very responsive to thermostimulation, it is immersed in 54 ± 1 ℃ of hot water can produce the water surface reaction that bounces back out behind the certain hour, and above-mentioned reaction is confirmed as the index of reflection pain intensity.It is the threshold of pain that mouse tail is immersed in the hot water timing definition that occurs to it till above-mentioned reaction.Analgesic can prolong the time that the pain reaction appears in mice, reflect its analgesic effect, so this model can be used for estimating the analgesic effect of medicine.Whether each administration group of statistical software comparison and blank control group exist significant difference to the influence that receives examination group mice pain threshold.
3, experimental result
(1) to the influence of hot plate mice
In the experiment of mice hot plate, to compare with model control group, there is tangible prolongation effect in the mice pain response time that PAME20mg/kg, 40mg/kg, three dosage of 80mg/kg caused thermostimulation in 2 hours, and drug effect has good persistency.The mice hot plate experimental result of blank control group, positive control drug group, the basic, normal, high dose groups of PAME sees table 4 for details.
Table 4 PAME is to the influence (n=10) in pain response time of hot plate mice
Annotate: compare * P＜0.05, * * P＜0.01 with model group.
(2) hot water is stimulated the influence of mice
In the experiment of mice hot water whipping, to compare with the blank group, Compound P AME40mg/kg, two dosage of 80mg/kg have tangible prolongation effect to the mice pain response time that thermostimulation causes.And this chemical compound still had good analgesic effect in 2 hours after medication.The mice hot water whipping experimental result of blank control group, positive control drug group, the basic, normal, high dose groups of PAME sees table 5 for details.
Table 5PAME stimulates the induced mice influence (n=10) in pain response time to hot water
Annotate: compare * P＜0.05, * * P＜0.01 with model group.
4, conclusion
Above result of the test shows, PAME in 120min significant prolongation mice licking the sufficient time on hot plate; Also obviously increase the stimulation time of hot water, and be tangible dose effect dependence mousetail.These experimental result promptings, PAME has the obvious suppression effect to thermostimulation pain.
(3) rat machinery tenderness test
1, experiment material
(1) medicine
PAME: receive the reagent thing, pale yellow powder, purity 91.31% is provided by pharmacognosy teaching and research room of Cellege of Pharmacy, No. 2 Military Medical Univ., PLA.Test lot number: 20090501.It is subsequent use to be mixed with 0.125%, 0.25%, 0.5% medicinal liquid respectively with the distilled water that contains 0.5%CMC during experiment.
Medicine and reagent: formaldehyde (analytical pure), acetic acid (analytical pure) [Shanghai traditional Chinese medicines group chemical reagent responsibility company limited]; Morphine, Allylnoroxymorphone, methylene blue (buying on behalf) by the religion Bao Chu of The 2nd Army Medical College; Aspirin sodium, tramadol, pentobarbital sodium (Beijing Sihuan Pharmaceutical Co., Ltd).The Configuration Values respective concentration is subsequent use during experiment.
The SD rat, male, body weight 180220g, laboratory animal production licence number: SCXK (Shanghai)-2007-003.Provide by Second Military Medical University, PLA Animal Experimental Study center.The quarantine back is subsequent use.
2, experimental technique
Select for use 180～220g male rat to carry out mechanical tenderness experiment.Rat is positioned in the stationary magazine creel, makes animal be in the comfortable state that plays fixation again, use YLS-3E electronics tenderness appearance to measure the threshold of pain of rat.With flat type pressure head the rat tail is exerted pressure, when animal because of pain occur toot cry or the force value of demonstration when the struggling pain threshold of animal for this reason.1 basic pain threshold is whenever surveyed at a distance from 20min in the basic threshold of pain of the preceding mensuration of experiment beginning, and the average pain threshold of getting 3 mensuration numerical value is as the basic threshold of pain.Rat carries out 40min before the tenderness experiment, gives the rat administration of fasting 15h with basic, normal, high dosage-20mg/kg, 40mg/kg, the 80mg/kg of PAME with the mode of irritating stomach.(10mg/kg s.c.) carries out the subcutaneous injection administration as positive control drug 30min before the experiment beginning to mice to morphine.Observe the analgesic effect of Compound P AME behind the administration 40min.
3, experimental result
In the experiment of rat machinery tenderness, reach pain thresholding equal no significant difference in basis between group before each treated animal administration.After the administration 40 minutes, PAM20mg/kg, 40mg/kg, four dose groups rats pains of 80mg/kg thresholdings and significantly risings of blank control group had significant difference on the statistics.The result sees table 6 for details.
Table 6PAME is to the influence in rat machinery tenderness response time (mean ± SEM)
Annotate: compare * P＜0.05, * * P＜0.01 with model group.
4, conclusion
Above experimental result shows, the PAME significant prolongation rat tenderness of mechanical stimulus is stood the time, and be tangible dose-effect dependency.The experimental result prompting, PAME has the obvious suppression effect to mechanical tenderness.
The preparation of embodiment 3. casticin capsules
(1) prescription
(2) preparation technology takes by weighing the principal agent and the adjuvant of recipe quantity respectively by above prescription, crosses behind 80 mesh sieves according to the method mix homogeneously that progressively increases of equivalent under the formulation and technology item, and it is encapsulated with No. 2 capsule boards craft to get above-mentioned medicated powder, makes 9812 of capsules altogether, and yield rate is 98.12%.
The preparation of embodiment 4. casticin injectable powder
Get casticin 30mg, add dextran 30g, add 500ml water for injection, stir and make its dissolving; Add the injection water to 2000ml, add the 3.0g needle-use activated carbon, fully stirred 30 minutes; Decarbonization filtering; With 0.22 μ m filtering with microporous membrane; Be filled in the aseptic cillin bottle, every bottle of 2ml partly rolls plug; Lyophilization, tamponade is rolled lid and is got final product again.
The preparation of embodiment 5. casticin injectable powder
Get casticin 60mg, add 500ml water for injection, stir and make its dissolving; Add the injection water to 1000ml, add the 1g needle-use activated carbon, fully stirred 30 minutes; Decarbonization filtering; With 0.22 μ m filtering with microporous membrane; Lyophilization gets sterilized powder, is distributed into 1000 bottles.
Claims (1)
1. the application of casticin in the preparation analgesic.
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| CN105168201A (en) * | 2015-09-30 | 2015-12-23 | 南通大学 | Application of vitexin in preparation of drug for treating postoperative pain |
| CN105168201B (en) * | 2015-09-30 | 2017-11-07 | 南通大学 | Application of the Vitexin in pain medication after preparing iatrotechnics |
| CN107260720A (en) * | 2017-06-08 | 2017-10-20 | 南方医科大学 | Application of the casticin in medicament for resisting ulcerative colitis is prepared |
| CN109771414A (en) * | 2019-03-15 | 2019-05-21 | 苏州大学附属第二医院 | A kind of pharmaceutical composition for treating haemorrhagic shock |
| CN109771414B (en) * | 2019-03-15 | 2021-04-20 | 苏州大学附属第二医院 | Pharmaceutical composition for treating hemorrhagic shock |
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Application publication date: 20121024 |