CN102772410A - Cocktail-like composite analgesic drug - Google Patents
Cocktail-like composite analgesic drug Download PDFInfo
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- CN102772410A CN102772410A CN2011101186771A CN201110118677A CN102772410A CN 102772410 A CN102772410 A CN 102772410A CN 2011101186771 A CN2011101186771 A CN 2011101186771A CN 201110118677 A CN201110118677 A CN 201110118677A CN 102772410 A CN102772410 A CN 102772410A
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- bupivacaine
- epinephrine
- morphine
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Abstract
The invention provides a cocktail-like composite analgesic drug which contains bupivacaine, morphine and epinephrine, wherein a weight ratio of bupivacaine to morphine to epinephrine is 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081. The invention also provides a preparation method for the cocktail-like composite analgesic drug. According to the invention, injection drugs are selected and used for analgesia so as to ensure that experiment animals receive timely and sufficient analgesic treatment; therefore, the possibility that the experiment animals do not eat all the given food during oral administration is avoided, and the occurrence possibility of complications caused by a great drug administration amount at a time due to chewing of a slow release drug by the experiment animals is also avoided.
Description
Technical field
The present invention relates to the pharmaceutical chemistry field, relate in particular to a kind of analgesic, the compound analgesic of particularly a kind of cocktail type.
Background technology
The welfare of laboratory animal and ethics are more and more causing the attention of laboratory animal scientist and Animal Protection Association in recent years.Analgesia is the important step that improves the laboratory animal welfare, and the foreign scholar starts to walk early than China to laboratory animal peri-operation period analgesia research, but the correlational study achievement seldom, still is in the exploratory development stage.Domestic scholars to its understanding and attention degree not enough, still be in the analgesia Application Research stage in the operation.Along with paying attention to gradually improving the laboratory animal social benefit both at home and abroad, can be expected in following a period of time, laboratory animal peri-operation period analgesia research will be a crucial problem.And about all rarely seen both at home and abroad report of laboratory animal peri-operation period analgesic research; Carrying out the analgesia of laboratory animal peri-operation period has great importance to the welfare that improves laboratory animal; Actively develop this research and therefore become very critical and urgent, help to obtain best experimental studies results.
Summary of the invention
The object of the present invention is to provide the compound analgesic of a kind of cocktail type, the compound analgesic of described this cocktail type will solve the technical problem that the safety of animal analgesic is low in the prior art, analgesic effect is not good.
The invention provides the compound analgesic of a kind of cocktail type, it is characterized in that: contain bupivacaine, morphine and epinephrine, wherein bupivacaine, morphine and adrenergic weight ratio are 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081.
Further, also contain sodium chloride, described bupivacaine, morphine and epinephrine, wherein the weight ratio of bupivacaine, morphine, epinephrine and sodium chloride is 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081: 8-11.
Further; Also contain deionized water; Described bupivacaine, morphine and epinephrine, wherein the weight ratio of bupivacaine, morphine, epinephrine, sodium chloride and deionized water is 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081: 8-11: 1000.
Further, described bupivacaine, morphine and epinephrine, wherein the weight ratio of bupivacaine, morphine, epinephrine, sodium chloride and deionized water is 1.5: 0.1: 0.0000075: 9: 1000.
The present invention also provides the method for preparing of the above-mentioned compound analgesic of a kind of cocktail type; Comprise a step that proportionally takes by weighing each composition; The step of a preparation bupivacaine solution; The step of a preparation epinephrine solution, the step of a preparing normal saline is mixed bupivacaine solution, morphine and epinephrine solution earlier; Adopting normal saline dilution then, is 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081: 8-11 until the weight ratio of bupivacaine, morphine, epinephrine, sodium chloride and deionized water: 1000.
Concrete; The method for preparing of the above-mentioned compound analgesic of a kind of cocktail type comprises a step that proportionally takes by weighing each composition; A preparation mass concentration is the step of 0.25% bupivacaine solution, the step of a preparation 0.3ng/ml epinephrine solution, the step of a preparing normal saline; Earlier 240mg bupivacaine solution, 4mg morphine and 1ml epinephrine solution are mixed, adopt normal saline to be diluted to 40ml then.
The present invention compares with prior art, and its effect is actively with tangible.The present invention selects injection type medicine analgesia for use; Guarantee laboratory animal in time, capacity receive analgesia therapy; Avoid the contingent laboratory animal of oral administration route administered agents all not to be eaten, also avoided it slow releasing pharmaceutical to be chewed the excessive contingent complication of disposable drug dosage that is caused simultaneously.
This experiment is benefited our pursuits at laboratory animal peri-operation period ease pain; The comprehensive analgesia scheme that is proposed is practical; Cost; Improve the laboratory animal welfare work and have certain facilitation improving us, rejected laboratory animal, will help to obtain objective more comprehensive experimental studies results because of a series of side effect that pain causes.
The specific embodiment:
Embodiment 1 materials and methods
1.1 laboratory animal and material
Totally 40 of regular grade Beagle dogs, 8 monthly ages, body weight 8-11kg, male and female half and half, available from last marine rainbow skin of bamboo dog class plant [SCXK (Shanghai) 2007-0006], sub-cage rearing, room temperature is controlled at (18 ± 2) ℃ [SYXK (Shanghai) 2007-0003]; The main medicine cox 2 inhibitor that eases pain is special anti-available from Pfizer company.
1.2 animal experiment method
1.2.1 self-control dog fracture of tibia internal fixation model
Be damage model with the dog fracture of tibia at first, the trauma model method for preparing is for to obtain so that 1/3 intersection was cross-section on electric saw was in the dog tibia, and then carries out dog fracture of tibia open reduction steel plate screw internal fixation.
1.2.2 analgesia method:
Laboratory animal is divided into four groups at random, every group respectively at once after surgery, 1h, 6h, 12h and 24h, 2d, 3d, 5d, 7 days record pain situation.
Experimental group one: art began to give the intramuscular injection anti-inflammation and analgesic drugs by body weight in preceding 30 minutes; The special anti-40mg of cox 2 inhibitor; Anesthesia gives by present conventional method in the art; Operation promptly gives the compound analgesic of cocktail type at periosteum, soft tissue surrounding injection before finishing, and concrete prescription is: the mixed liquor of 0.25% bupivacaine 240mg/ morphine 4mg/ epinephrine 0.3ng (1: 1000) is diluted to 30ml with normal saline.Thereafter the per 12 hours special anti-40mg of injection totally 6 times, promptly were maintained until postoperative 3.
Experimental group two: give the intramuscular injection anti-inflammation and analgesic drugs before the art, the cox 2 inhibitor spy is anti-, and anesthesia gives by present conventional method in the art, and operation finishes promptly no longer to give the pain relieving measure.
Experimental group three: according to the scheme of routine operation narcotic analgesic in the past, only when operation, give anaesthetic, to the pain reaction situation, promptly observation experiment dog pain is more violent, promptly gives intramuscular injection analgesic drug product morphine again according to animal in the operation back.
Experimental group four: according to the scheme of routine operation narcotic analgesic in the past, promptly only when operation, give anaesthetic, operation finishes no longer to give any pain relieving measure.
1.2.3 the result observes and measures
Laboratory animal pain situation is carried out observed and recorded, part index number is carried out statistical analysis relatively.
1.3 statistical analysis
Experimental result is judged the pain difference with the X 2 test analysis with odds ratio (OR), and statistical software adopts SPSS 11.5for Windows XP.
2 results
2.1 body weight and diet are taken in situation
Animal subject pain situation directly influences the variation of the intake and the body weight of its food and water.Table 1 shows, four groups of laboratory animal diet are taken in and minimizing in various degree all appears in body weight.There is difference in its minimizing degree, and the 72h intake of dog is higher than other three groups in the experimental group one, especially is higher than the experimental group four (P＜0.05) of routine operation narcotic analgesic.Accordingly, when testing 7 days, the losing weight of experimental group one dog compared to other three groups, especially comparing with experimental group four is minimum (P＜0.05).
Table 1 laboratory animal body weight and diet are taken in situation
*P＜0.05
2.2 breathe and the situation of trembling
Animal subject pain can cause breathes and the muscular tremor variation.Table 2 shows that the respiratory variations in various degree and the generation of trembling all appear in four treated animals.Between each group both a situation arises shows to have the difference of statistical significance.
Table 2 laboratory animal 72h breathes and the situation of trembling
*P＜0.05
2.3 behavior reaction situation when socialization's behavior and irriate
The variation of behavior reaction when animal subject pain can cause its socialization's behavior and irriate.Table 3 shows that socialization's behavior of experimental group one animal (interaction of colony's equity) is higher than other three groups, especially is higher than the experimental group four (P＜0.05) of routine operation narcotic analgesic.Aspect the behavior reaction, the reaction natural rate of interest of experimental group one and experimental group two is identical, all is higher than other two groups when irriate, and is significantly higher than experimental group four (P＜0.05).
Behavior reaction situation when socialization's behavior of table 3 laboratory animal and irriate
*P＜0.05
3 conclusions
This studies selected laboratory animal pain model is laboratory animal one of the operation of pain the most, because in pain model was made, laboratory animal will stand triple wounds: cut skin, cut deep fascia and fracture of tibia; Moreover, fracture repair is still needed and is wanted Retracting repositioning and boring steel plate to fix, and these operations all can cause having an intense pain.When previously we carried out meniscus injury reconstruction experimentation, though be moderate pain operation in the bone surgery, complication such as dead, that body weight obviously alleviates also took place in experimental dog.It is thus clear that the pain problem that laboratory animal is participated in the scientific research is the problem that we must attract great attention and properly settle.
Among the present invention, we adopt the multi-mode analgesia, have obtained better curative effect.In the experimental group, observed each item physical signs and reaction of animals all obviously are lighter than matched group, and promptly our present great majority relate to the analgesia mode of laboratory animal.Countless experience and lessons prove; The previously the sort of painless and analgesia mode that gives of laboratory animal that only in the experimental implementation process, keeps; Often make laboratory animal need experience painful operation wound process, pathological reaction such as cause a series of anorexia, mood changes that cause because of pain even lose weight.These untoward reaction the lighter can cause a series of physiology untoward reaction of laboratory animal, and weight person can cause laboratory animal dead, and waste experimentation funds are also unfair to laboratory animal.
The present invention selects injection type medicine analgesia for use; Most important reason be guarantee laboratory animal in time, capacity receive analgesia therapy; Avoid the contingent laboratory animal of oral administration route administered agents all not to be eaten, also avoided it slow releasing pharmaceutical to be chewed the excessive contingent complication of disposable drug dosage that is caused simultaneously.
Through this comparative study; Our cognition is; Employing peri-operation period analgesia, key factor are that the scientific research personnel need correct and only previously thinks and just need give analgesic even experimental implementation is accomplished at si dol urg, needn't comprehend the cacodoxy of laboratory animal pain; Should be fully recognized that in time, on time and use analgesic safer and more effective, the intensity of required analgesic and dosage also can be minimum, help us to obtain more science experimental result accurately more.
The present invention confirms early stage, leading active prevention property application analgesic, obtains analgesic effect preferably, has operability.
The inventor thinks, and is more loaded down with trivial details about dog pain appraisal procedure abroad, is not easy to analyze relatively; Under the situation the about at home understanding of laboratory animal ease pain also relatively being lagged behind; Choose wherein several indexs and assess, have better operability, also help progressively and international joint.Improve the laboratory animal welfare work and be of great significance improving us.
Claims (6)
1. compound analgesic of cocktail type, it is characterized in that: contain bupivacaine, morphine and epinephrine, wherein bupivacaine, morphine and adrenergic weight ratio are 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081.
2. the compound analgesic of a kind of cocktail type as claimed in claim 1; It is characterized in that: it is characterized in that: also contain sodium chloride; Described bupivacaine, morphine and epinephrine, wherein the weight ratio of bupivacaine, morphine, epinephrine and sodium chloride is 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081: 8-11.
3. the compound analgesic of a kind of cocktail type as claimed in claim 1; It is characterized in that: it is characterized in that: also contain deionized water; Described bupivacaine, morphine and epinephrine, wherein the weight ratio of bupivacaine, morphine, epinephrine, sodium chloride and deionized water is 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081: 8-11: 1000.
4. the compound analgesic of a kind of cocktail type as claimed in claim 3; It is characterized in that: it is characterized in that: described bupivacaine, morphine and epinephrine, wherein the weight ratio of bupivacaine, morphine, epinephrine, sodium chloride and deionized water is 1.5: 0.1: 0.0000075: 9: 1000.
5. the method for preparing of the compound analgesic of the described a kind of cocktail type of claim 1; It is characterized in that: comprise a step that proportionally takes by weighing each composition; The step of a preparation bupivacaine solution; The step of a preparation epinephrine solution, the step of a preparing normal saline is mixed bupivacaine solution, morphine and epinephrine solution earlier; Adopting normal saline dilution then, is 1.3-1.7: 0.08-0.12: 0.0000071-0.0000081: 8-11 until the weight ratio of bupivacaine, morphine, epinephrine, sodium chloride and deionized water: 1000.
6. the method for preparing of the compound analgesic of a kind of cocktail type as claimed in claim 5; It is characterized in that: comprise a step that proportionally takes by weighing each composition; A preparation mass concentration is the step of 0.25% bupivacaine solution, the step of a preparation 0.3ng/ml epinephrine solution, the step of a preparing normal saline; Earlier 240mg bupivacaine solution, 4mg morphine and 1ml epinephrine solution are mixed, adopt normal saline to be diluted to 40ml then.
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| CN2011101186771A CN102772410A (en) | 2011-05-09 | 2011-05-09 | Cocktail-like composite analgesic drug |
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| CN2011101186771A CN102772410A (en) | 2011-05-09 | 2011-05-09 | Cocktail-like composite analgesic drug |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105030775A (en) * | 2015-07-13 | 2015-11-11 | 广州金中健医疗器材有限公司 | Non-addiction local anesthesia analgesic sustained-release drug delivery system and method for preparing same |
-
2011
- 2011-05-09 CN CN2011101186771A patent/CN102772410A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| 张俊等: "人工全膝关节置换术中关节周围注射镇痛药物和术后持续性冷冻压迫的疗效分析", 《中国骨与关节损伤杂志》 * |
| 张俊等: "人工全膝关节置换术中关节周围注射镇痛药物对术后痛的效果", 《中国组织工程研究与临床康复》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105030775A (en) * | 2015-07-13 | 2015-11-11 | 广州金中健医疗器材有限公司 | Non-addiction local anesthesia analgesic sustained-release drug delivery system and method for preparing same |
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Application publication date: 20121114 |