CN102920706B - Emulsified isoflurane compound anesthetic for dogs and preparation method thereof - Google Patents
Emulsified isoflurane compound anesthetic for dogs and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to veterinary medicine preparation technology and provides an emulsified isoflurane compound anesthetic for dogs and a preparation method thereof. The emulsified isoflurane compound anesthetic for the dogs is formed by isoflurane, citric acid fentanyl citrate, lidocaine hydrochloride and 30% of fat emulsion. The isoflurane, the citric acid fentanyl citrate and the lidocaine hydrochloride are dissolved in the 30% of fat emulsion and then potted and sealed in ampoule bottles, after full oscillation, water bath and sterilization, the emulsified isoflurane compound anesthetic for the dogs is obtained. The anesthetic is rapid in anesthesia induction, safe and effective in the process of anesthesia, strong in anesthesia controllability, small in toxic and side effects, convenient to use, and especially suitable for complex operations or long-time operations, and the dogs can revive rapidly.
Description
Technical field
The invention belongs to technical field of animal remedy preparation, relate generally to a kind of dog venoclysis Emulsified Isoflurane compound anesthetic and technology of preparing.
Background technology
Anaesthetic generally can be divided into inhalation anesthetic and intravenous anesthetic two kinds.Although existing inhalation anesthesia has controllability affect the advantages such as little by force, on body, but need by special anesthesia equipment when using, be equipped with single-minded inhalation anesthesia Volatile anesthetic, not only formality is very loaded down with trivial details, and equipment and medicine very expensive, increase anesthesia cost, most animals hospital is difficult to apply at home, moreover because the kind of dog numerous (factor such as build, upper respiratory tract anatomical features) and veterinary anaesthetic personnel are to inhalation anesthesia technology Grasping level, also have impact on the development of inhalation anesthesia in animal clinical anesthesia field.
Compared with inhalation anesthesia, intravenous anesthetic have non-environmental-pollution, dosage accurately, the advantage of definite effect.The target controlled infusion technology of current three intravenous anesthetics, can simulate the change of body blood drug level and accurately give medicine, can realize the depth of anesthesia of expecting, postoperative rapid recovery recovers; Side effect is less, without hepatic and renal function injure.
At present, animal clinical anesthesia development trend is balanced anesthesia, namely multi-medicament use in conjunction, not only can reasonable control depth of anesthesia, meet the needs of operation, the consumption of single medicine can also be reduced, reduce drug accumulation, alleviate the excessive side effect caused of drug level, such as balanced anesthesia etc.Therefore, for the action character of various three intravenous anesthetics, preparation compound formulation is the major trend of current anesthesia clinical development, can not only avoid that single medicine using dosage is excessive, toxic and side effects large like this, and can reach good anaesthetic effect.
Summary of the invention
Object of the present invention is exactly for above-mentioned prior art Problems existing, clinical needs are anaesthetized in conjunction with dog class, and develop a kind of dog Emulsified Isoflurane compound anesthetic, by by Emulsified Isoflurane, fentanyl, lignocaine three kinds of medicines carry out scientific composition, reach reasonable compatibility, produce good anaesthetic effect, the side effect of each single medicine is down to minimum simultaneously, overcome inhalation anesthesia complicated operation, somewhat expensive, equipment and technology requires high, and administered intramuscular is difficult to control depth of anesthesia and hold time, easy generation is significantly breathed to be affected with blood circulation, be difficult to be applied to the technical barriers such as complicated and prolonged operations.
The object of the present invention is achieved like this:
1. the Emulsified Isoflurane compound anesthetic of dog described in is made up of isoflurane, fentanyl citrate, lidocaine hydrochloride and 30% fat milk, in every 100mL dog Emulsified Isoflurane compound anesthetic, the content of each composition is isoflurane 8mL, fentanyl citrate 20 μ g, lidocaine hydrochloride 48 mg, surplus is 30% fat milk;
2. the preparation method of Emulsified Isoflurane compound anesthetic of dog described in, is dissolved in successively by isoflurane, fentanyl, lignocaine in 30% fat milk, and embedding, in 10 mL ampoule bottles, is fully vibrated, and water-bath, final sterilization obtains this agent.
The present invention compared with prior art has the following advantages:
1. induction of anesthesia is rapid, induction time 11.52 ± 3.47 s, and the anesthesia maintenance time needs according to operation and determines (reaching 6h most in experiment), and recovery time is 6.26 ± 1.21 min.Show the induction of this compound anesthetic rapidly steadily; Anesthesia maintenance is controlled flexibly; Revive fast, performance without exception (excited, sleep again).
2. pair major physiological parameter influence
Have certain influence to normal body temperature, after showing as injection, body temperature starts to decline, and during to anesthesia 50min, body temperature is down to minimum, compares with 0min, reduced by only 1.8 DEG C; Heart rate 5min after injection reaches peak value, and comparatively 0min adds 10.66%.Start steady decline afterwards, during anesthesia 20min, return to normal level.First raise after respiratory frequency injection and decline afterwards, substantially recover normal level to during anesthesia 20min.Blood oxygen saturation show as the initial stage decline, after injection, 5min is down to minimum, after gradually recover and close to normal level, in whole anaesthesia process, blood oxygen saturation is equal more than 93%.Blood pressure starts to reduce after injection, to the minimum of being down to anesthesia overall process during 5min, raises gradually subsequently, 10-60min after injection, and blood pressure is compared with 0min, and diversity is not all significantly (p>0.05).
3. on the impact of hepatic and renal function
After anesthesia, each time point ALT, AST, BUN activity compares with 0 h respectively, diversity remarkable (p >0.05), and the activity of different time points AST, ALT, BUN is also all within normal range.Result shows, dog Emulsified Isoflurane compound anesthetic has no significant effect dog hepatic and renal function.
4. simple to operate, can intravenous injection, anaesthetize for rapid induction; Venoclysis, for maintaining anesthesia, can arrange Infusion Time and dosage flexibly according to operation needs, for complicated or that the time is long operation.
Accompanying drawing explanation
Fig. 1 is the every physiological indexes situation of dog after anesthesia.
Fig. 2 is dog hepatic and renal function index situation of change after anesthesia.
In figure T1, T2, T3, T4, T5, T6, T7, T8 represent 0 respectively, 0.5,1,2,6,12,24,48h equi-time point.
Detailed description of the invention
Below embodiment of the present invention is described in detail.
1. the Emulsified Isoflurane compound anesthetic of dog described in is made up of isoflurane, fentanyl citrate, lidocaine hydrochloride and 30% fat milk, in every 100mL dog Emulsified Isoflurane compound anesthetic, the content of each composition is isoflurane 8mL, fentanyl citrate 20 μ g, lidocaine hydrochloride 48 mg, surplus is 30% fat milk;
2. the preparation method of Emulsified Isoflurane compound anesthetic of dog described in, is dissolved in successively by isoflurane, fentanyl, lignocaine in 30% fat milk, and embedding, in 10 mL ampoule bottles, is fully vibrated, and water-bath, final sterilization obtains this agent.
The Emulsified Isoflurane compound anesthetic that the present invention relates to is a kind of novel general intravenous anesthesia medicine, and wherein fentanyl citrate is opioid receptor agonist, belongs to potent narcotic analgesic.Analgesic Mechanism is similar to morphine, but action intensity is 60 ~ 80 times of morphine.Compared with morphine, fentanyl citrate analgesic activity produces rapidly, holds time short, do not discharge histamine, affect little on cardiovascular function, stress during tracheal intubation can be suppressed, be usually used in the calmness before, during and after anaesthetizing and analgesia, also for pain that a variety of causes causes.Fentanyl citrate is weaker than morphine to the inhibitory action of breathing, but intravenous injection is too fast, easily suppresses to breathe.Lidocaine hydrochloride is the local anesthesia that medical and clinical is conventional, and being prevent and treat acute myocardial infarction and the concurrent rapid ventricular antiarrhythmic medicament of various heart disease at present, is the ventricular premature contraction of acute myocardial infarction, the drug of first choice that ventricular tachycardia and room property are trembled.Own scholar's successful Application lidocaine hydrochloride is used for intravenous injection after Postoperative Analgesia After, and the research of vein lidocaine hydrochloride analgesic is more and more subject to people's attention.Research finds that intravenous lignocaine plays analgesic activity by affecting periphery and central endings function, not only can be widely used in the treatment of pain and other Acute or chronic pain after postoperative pain, neuropathic pain, fibromyalgia, amputation, also can reduce inflammatory response reaction that tissue ischemia causes and alleviate and discharged and K by adenosine triphosphate by endothelium and vascular tissue's factor
+the tissue injury of the mechanism of action mediation of passage.
experiment effect
(1) laboratory animal
Healthy domestic dog 8, the 12-16 monthly age, male and female half and half, body weight 5.1 ± 0.2 kg, purchased from Harbin Qing Xi plant, carries out conventional immunity and anthelmintic when buying; ICR mice 300, male and female half and half, body weight is 22 ± 2g, purchases in university of TCM of Heilongjiang Province Experimental Animal Center, and raise under identical conditions and test for 4 weeks, in whole process of the test, feeding and management condition is consistent.
(2) prescription test
1. medicine primary screening test
By the contrast test of anaesthetizing dog, Anesthesia induction, anesthetic stage, the waking up period of the various combination of comprehensive analysis, calmness, analgesia, physical signs such as flesh pine effect and breathing, pulse, body temperature etc., find that the compound formulation that be made up of Emulsified Isoflurane, fentanyl, lignocaine is obviously better than other various combinations, therefore fix tentatively using Emulsified Isoflurane, fentanyl, lignocaine as the main component of combined anesthesia preparation;
2. component is determined and ratio exploratory experiment
With the various combination be made up of Emulsified Isoflurane, fentanyl, lignocaine, venoclysis is carried out to dog, observe the situation such as biological reflection case and calmness, analgesia, flesh pine, comprehensive analysis and inspection is carried out to the anesthetic action of various combination, the ratio of each component of continuous adjustment and dosage, Preliminary screening goes out using Emulsified Isoflurane, fentanyl, lignocaine as the component of compound formulation, and to draft proportions be 5:3:4.
Table 1 factor level table
3. orthogonal test
To design in conjunction with the observation of anaesthetic effect in trial test according to Three factors-levels Orthogonal Experiment and Design principle.3 factors in combined anesthesia preparation are Emulsified Isoflurane, fentanyl, lignocaine, and 3 levels are high, medium and low.According to orthogonal table L9 (3
3) white mice is divided into 9 test group at random, according to the samples selection principle in statistics standard and pharmacology design, each test group selects white mice 30, and lumbar injection 0.025mL/g, analyzes the impact of each ingredient on anaesthetic effect according to orthogonal table.
After white mice anesthesia, righting reflex loss reaches at more than 1min person is judged to be the positive in 30min.
As shown in Table 2: Emulsified Isoflurane during effect is better than when high dose, low dosage; Fentanyl effect when low dosage is better than height, middle dosage; Lignocaine effect when middle dosage is better than high and low dose.Comparative analysis experiment effect, wherein Emulsified Isoflurane role is larger.Therefore select the combination 7,8 and 9 that righting reflex effect is best, enter next step orthogonal decisive confirmatory experiment as prescription 1,2 and 3.
Table 2 white mice Orthogonal experiment results (n=30)
Note: * represent often row three level list drug effect fruit in maximum, E
1, E
2, E
3for the drug effect sum of the basic, normal, high level of this medicine.
4. orthogonal decisive confirmatory experiment
(1) sedation effect monitoring and evaluation criterion
After white mice anesthesia, the sedation effect respectively after observation medication when 5min, 10min, 20min and 30min.Observation is blinked, ear is dynamic, body is dynamic, head and neck is dynamic, tail is dynamic.
To sonic stimulation significant reaction, before administration, note "+"; To sonic stimulation bradykinesia, note " ± "; Reactionless to sonic stimulation, note "-".
Methods of marking: "+" meter 0 point, " ± " meter 2 points, "-" meter 4 points.
(2) analgesic effect monitoring and evaluation criterion
Evaluate mainly through acupuncture muffle portion, trunk, extremity top, claw, afterbody.
Acupuncture each portion pain reaction is obvious, note "+"; Pain reaction is blunt, note " ± "; Pain reaction disappears, note "-".
Methods of marking: "+" meter 0 point, " ± " meter 2 points, "-" meter 4 points.
(3) flesh pine effect monitoring and evaluation criterion
Viewing head cervical region, tail, extremity, masseter and abdominal wall muscle relax level.
Turn one's head and turn round reaction as occurred when mentioning with tweezers folder tail, extremity appearance is obviously slided, stimulate extremity still can creep, remember "+"; Folder tail occurs when mentioning that rotary head, simultaneously extremity slightly slide, note " ± "; Without turning one's head and turning round reaction, note "-".
Folder ear when mentioning as tail be flexible to horizontal level or upwarp time, note "+"; As bending reaction appears in tail, note " ± "; Tail naturally droops, note "-".
Clamp ear with tweezers to mention, as struggling appears in extremity, note "+"; Extremity slightly slide, note " ± "; Extremity naturally droop, note "-".
If postabdomen is without significant change when folder ear is mentioned, note "+"; Postabdomen slightly expands lax, note " ± "; Postabdomen obviously expands lax, note "-".
Masseter is lax gently to be pulled on, lower jaw, and oral cavity can smooth opening, note "+"; Oral cavity can be opened, but very soon can recuperator, note " ± "; Recuperator immediately after can not opening or open, note "-".
Methods of marking: "+" meter 0 point, " ± " meter 2 points, "-" meter 4 points.
The observation (n=15) of anaesthetic effect after table 3 white mice injection 5,10,20 and 30min
By experimental result in table 3, can find out that prescription 1 is better than prescription 2 and 3, particularly at ease pain.Determine that best prescription is prescription 1 thus.
5. optimizing prescriptions is to the Anesthetic Effect of dog
(1) anesthesia
12h fasting before dog test, before test, 2h prohibits water, entering test site until it conforms after peace and quiet, measures its physiological indexes, comprises respiratory frequency (RR), heart rate (HR), mean arterial pressure (MBP), arterial oxygen saturation (SPO2), body temperature (RT) etc.Weigh subsequently, settle venous detaining needle respectively at dog two forelimb arm head vein, intramuscular injection 0.01 mg/kg atropine, at the uniform velocity induces to intravenous push Emulsified Isoflurane compound anesthetic in 10 s according to 1mL/Kg dosage after 15min.After righting reflex loss, connect Iv pump rapidly in left side venous detaining needle, adjustment flow velocity, carries out venoclysis according to the dosage of 5mL/Kg/h, starts timing simultaneously, after entering anesthetic stage, is lifted to Baoding that retainer lies on the back, connects anesthesia monitor.
Gather venous blood 1 mL respectively at different time points by the venous detaining needle being placed in offside arm head vein, after placing 1 h, centrifugal 10 min of 3000 rpm, are separated and manage to EP without the serum of chyle and haemolysis.UniCel DxC 800 Synchron automatic clinical chemistry analyzer is adopted to detect.
(2) monitoring in period is anaesthetized
Induction of anesthesia time 11.52 ± 3.47 s, anesthesia maintenance time 1 ~ 6h, recovery time is 6.26 ± 1.21 min.
(3) anaesthetic effect (ease pain, calm, flesh is loose) monitoring
Mark by anaesthetic effect (ease pain, calm, flesh the is loose) standards of grading of table 4 dog, anaesthetic effect must be divided into every score sum.
Table 4 eases pain, calm, the loose standards of grading of flesh
Anaesthetic effect score is in table 5.
Table 5 dog anaesthetic effect Score Lists
Note: shoulder mark capitalization difference represents significant difference,
p< 0.05.
6. physiological functional moni-toring
T presents downward trend gradually, and after other indexs are all embodied in injection, the initial stage raises, and returns to normal level (see table 6) afterwards.
Every physiological parameter change (min, n=8) of rear dog anaesthetized by table 6
Note: compared with 0 minute, * represents significant difference,
p< 0.05.
7. hepatic and renal function monitoring
Each time point ALT, AST, BUN activity is respectively compared with basic value, diversity is not all significantly (P>0.05), there is change to a certain degree in ALP, CK, CREA, CHOL after being anesthetized 1h, with the poor opposite sex of basic value remarkable (P<0.05), return to foundation level (P>0.05) afterwards gradually.Concrete outcome is in table 7.
Hepatic and renal function index change (h, n=8) of rear dog anaesthetized by table 7
Note: compare with 0 h, * represents significant difference
Claims (2)
1. a dog Emulsified Isoflurane compound anesthetic, it is characterized in that described dog Emulsified Isoflurane compound anesthetic is made up of isoflurane, fentanyl citrate, lidocaine hydrochloride and 30% fat milk, in every 100mL dog Emulsified Isoflurane compound anesthetic, the content of each composition is isoflurane 8mL, fentanyl citrate 20 μ g, lidocaine hydrochloride 48 mg, surplus is 30% fat milk.
2. the dog preparation method of Emulsified Isoflurane compound anesthetic as claimed in claim 1, it is characterized in that isoflurane, fentanyl, lignocaine to be dissolved in 30% fat milk successively, embedding, in 10 mL ampoule bottles, is fully vibrated, water-bath, final sterilization obtains this agent.
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| 犬静脉注射乳化异氟醚最低肺泡有效浓度的研究;杨小霖 等;《临床麻醉学杂志》;20060331;第22卷(第3期);第204-206页，标题、摘要、引言部分，第204页"材料与方法" * |
| 静脉注射利多卡因及利多卡因复合芬太尼对异氟醚麻醉犬的血气影响;李德文 等;《中国兽医杂志》;20120922;第48卷(第09期);第64-67页，摘要 * |
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Inventor after: Fan Honggang Inventor after: Liu Haiyu Inventor after: Li Xuejiao Inventor after: Jiang Sheng Inventor after: An Haijun Inventor after: Lin Dongqi Inventor after: Guo Fengming Inventor after: Ji Wei Inventor after: Li Dapeng Inventor after: Zou Jing Inventor after: Zhang Jiantao Inventor before: Fan Honggang Inventor before: Li Xuejiao Inventor before: Jiang Sheng Inventor before: Lin Dongqi Inventor before: Guo Fengming Inventor before: Ji Wei Inventor before: Li Dapeng Inventor before: Zou Jing Inventor before: Zhang Jiantao Inventor before: Liu Haiyu |
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Free format text: CORRECT: INVENTOR; FROM: FAN HONGGANG JIANG SHENG LIN DONGQI GUO FENGMING JI WEI LI DAPENG ZOU JING ZHANG JIANTAO LIU HAIYU LI XUEJIAO TO: FAN HONGGANG JIANG SHENG AN HAIJUN LIN DONGQI GUO FENGMING JI WEI LI DAPENG ZOU JING ZHANG JIANTAO LIU HAIYU LI XUEJIAO |
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