CN114042075B

CN114042075B - Compound anesthetic and preparation method and application thereof

Info

Publication number: CN114042075B
Application number: CN202111190910.7A
Authority: CN
Inventors: 彭仕明; 陈武; 谢伟骏; 单芬; 黄勉; 萨家祺; 黄润基
Original assignee: Guang Zhoudongwuyuan
Current assignee: Guang Zhoudongwuyuan
Priority date: 2021-10-13
Filing date: 2021-10-13
Publication date: 2024-02-13
Anticipated expiration: 2041-10-13
Also published as: CN114042075A

Abstract

The invention relates to a compound anesthetic, a preparation method and application thereof, and relates to the technical fields of medicine research and development and clinical veterinarian. The compound anesthetic comprises anesthetic components, wherein the anesthetic components comprise the following raw materials: dexmedetomidine, telithromycin, zolazepam and butorphanol. The compound anesthetic can be applied to general anesthesia of felines and felines, can effectively solve the problems of cardiopulmonary function inhibition and ataxia existing in a waking period when the felines use TMZ compound anesthesia, can provide effective anesthesia time of 60-120min, and provides better effects of fixation, anesthesia, sedation, analgesia and muscle relaxation for feeding management, diagnosis and operation treatment of felines and felines, and has stable anesthesia effect.

Description

Compound anesthetic and preparation method and application thereof

Technical Field

The invention relates to the technical fields of medicine research and development and clinical veterinarian, in particular to a compound anesthetic and a preparation method and application thereof.

Background

Anesthesia of wild animals is an important link in the process of raising and managing wild animals in a housing, is the most basic link in operations such as raising wild animals in a housing, treatment of the wild animals in the housing, image inspection and the like, and is a precondition for emergency treatment of animal escape. The anesthetic is required to be used for animal anesthesia, has no irreversible damage to animals, has good effects of easing pain, tranquilizing and relaxing muscles, and has few side effects. Thus, the disease diagnosis, treatment and operation of the animal can be ensured to be smoothly carried out. Animal anesthesia has the advantages of simplifying animal fixing tools and saving manpower; avoiding animal injury or uneasiness during operation, ensuring smooth operation of aseptic operation and safety of human and animals; relaxing muscles, and facilitating health examination or operation; avoiding the bad stimulation of feeding operation or operation to reduce the body resistance of animals or to cause painful shock due to the cutting operation and viscera traction. In order to achieve the above-mentioned objects, there is a need for an animal anesthetic which achieves sufficient sedative, analgesic and muscle relaxant effects and minimizes adverse effects and toxic side effects of the anesthetic. The common methods of anesthesia used clinically are inhalation, oral, subcutaneous or intramuscular, intravenous, local, general, single, compound etc.

Wild felines and felines are large in size, strong in aggression, flexible in organism, and difficult to physically keep time, so that in clinical work of animal medicine, inhalation anesthesia is often adopted for treating diseases in felines and felines. However, since felines are not accessible even when they are ill, inhalation anesthesia is not readily available. And the trachea of the feline and the bear is large, so that a proper tracheal cannula is difficult to find, and the tracheal ligament on the back side of the feline is fragile, if the tracheal cannula is covered with the tracheal cannula, the tracheal soft tissue is torn due to the excessive air pressure, the respiratory system complications are caused, or the air is caused to enter loose tissues, so that serious animal medical accidents are formed.

Therefore, inhalation anesthesia works well, but for wild animals, it is necessary to use it on a intramuscular or intravenous anesthetic basis. In the past, liu Mianning, ketamine, and jingsong ling are commonly used, but the medicines have the side effects of easy repose, poor effects of sedation and analgesia and muscle relaxation, easy ataxia and the like during waking up. In recent years, some new medicines with small dosage, good anesthetic effect, low toxic and side effects, wide safety range and small interference to normal physiological functions have remarkably improved in clinical application, such as fentanyl, medetomidine, midazolam, etomidate and the like. However, no anesthetic has been shown to achieve satisfactory results in the anesthesia of felines and felines.

Disclosure of Invention

Aiming at the problems, the compound anesthetic provided by the invention can be applied to general anesthesia of felines and felines, can effectively solve the problems of cardiopulmonary function inhibition and ataxia existing in a waking period when the felines use TMZ compound anesthesia, can provide effective anesthesia time of 60-120min, and provides better effects of holding, anesthesia, sedation, analgesia and muscle relaxation for feeding management, diagnosis and operation treatment of the felines and the felines, and the anesthesia effect is stable.

In order to achieve the above purpose, the invention provides a compound anesthetic, which comprises anesthetic components, wherein the anesthetic components comprise the following raw materials: dexmedetomidine, telithromycin, zolazepam and butorphanol.

The inventor finds that the compound anesthesia is used as a clinical anesthesia technology for simultaneously or sequentially applying two or more anesthetic drugs, anesthesia methods and anesthesia therapies on felines and felines, can reduce the dosage of the anesthetic, reduce adverse reactions of the drugs, meet the requirements of animal transfer, operation and the like, simultaneously can reduce the adverse reactions brought by anesthesia to organisms to the minimum, provides perfect postoperative analgesia, and is beneficial to the recovery of health of organisms after operation. Where emergency awakening is desired or side effects occurring during awakening are reduced, the objective may be achieved by intramuscular or intravenous administration of the antagonist.

The temitamine and the zolazepam have better sedative effects on felines and bear animals, but have poor muscle relaxation and analgesic effects and shorter maintenance time, and the zolazepam has obvious respiratory depression effects, and ataxia and mania phenomena exist in the awakening period, and the phenomena are related to dosage; the dexmedetomidine has better sedative and muscle-relaxing effects, but has obvious respiratory depression, the butorphanol has good sedative and analgesic effects, and has no obvious respiratory and circulatory system depression, but the sedative and analgesic muscle-relaxing effects required by the operation are difficult to achieve by single use. Based on the reasons, the inventor selects the optimized combination of dexmedetomidine, telithromycin, zolazepam and butorphanol, can achieve the effects of long anesthesia maintenance time, full muscle relaxation, obvious sedation and analgesia, reduces the phenomena of inhibition of respiration and vomiting in an induction period, and can reduce the occurrence of ataxia and mania in a wake-up period.

In one embodiment, the anesthetic ingredient comprises the following raw materials in parts by weight:

the raw materials with the weight ratio have the advantages of reduced anesthesia cost, long anesthesia period, better sedative analgesic muscle relaxation effect, less side effects such as cardiopulmonary inhibition, reduced ataxia phenomenon in the awakening period, specific antagonist medicaments, emergency use and the like.

in one embodiment, the compound anesthetic further comprises a wake-up ingredient, the wake-up ingredient being atemezole.

Intramuscular injection and/or intravenous injection of the atimetazole in the awakening period can realize emergent awakening or reduce side effects during the awakening period, reduce the risk of anesthesia and shorten the awakening period.

The invention also provides application of the compound anesthetic in preparing a general anesthetized feline or bearberry preparation.

In one embodiment, the application comprises intramuscular injection and/or intravenous injection.

By adopting the anesthesia mode, the problem that animals are not easy to get close to during inhalation anesthesia can be solved, the occurrence probability of medical accidents can be reduced, and the anesthesia device is safer and more reliable than gas anesthesia.

In one embodiment, the feline comprises: tiger, leopard, lion, jaguar, seal, cloud, malecloud, asian cat, salon cat, eulynx, pony cat, canadian lynx, or spanish lynx.

In one embodiment, the use comprises administration at a dose of 0.40-0.65mg/kg body weight.

The compound anesthetic is applied by adopting the dosage, so that a stable anesthetic state can be realized on animals, and adverse reactions caused by excessive application dosage can be avoided.

The invention also provides the use of a waking ingredient in the compound anaesthetic, the use comprising administration at a dose of 0.05-0.15mg/kg body weight.

The recovery component is applied by the dosage, so that the recovery period of animals can be effectively shortened, and adverse reactions caused by excessive application dosage can be avoided.

Compared with the prior art, the invention has the following beneficial effects:

the compound anesthetic and the preparation method and application thereof can be applied to general anesthesia of felines and bear animals, can effectively solve the problem of ataxia existing in the heart and lung function inhibition and recovery period when the felines use TMZ compound anesthesia, can provide effective anesthesia time of 60-120min, and provides better effects of fixation, anesthesia, sedation, analgesia and muscle relaxation for feeding management, diagnosis and operation treatment of the felines and bear animals, and the anesthesia effect is stable. Intramuscular injection and/or intravenous injection of the atimetazole in the awakening period can realize emergent awakening or reduce side effects during the awakening period, reduce the risk of anesthesia and shorten the awakening period.

Detailed Description

In order that the invention may be readily understood, a more particular description of the invention will be rendered by reference to specific embodiments that are illustrated in the appended drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.

Definition:

the awakening period comprises the following steps: refers to the convalescence of anesthesia.

The source is as follows:

reagent: butoffei (lot number: 212/12 683 23, manufacturer: bioveta, a.s Komenskeho Ivanovice na Hane, czech republic), tiritamine/zolraxide (lot number: 20216UT6, manufacturer: verk, inc.), heparin sodium (lot number: 210625, manufacturer: hebei Changshan Biochemical Co., ltd.), dexmedetomidine (lot number: 1797542, manufacturer: expo manufacturing Co., finland Orion, inc.), pyridine, altemozole hydrochloride (lot number: 1927894, manufacturer: expo manufacturing Co., finland), deer-sleeping peaceftizor (dimethyl aniliothiazole, dihydro etorphine, manufacturer: china's Jib. Leku June research institute of Levone Levowealth), sterilized water for injection (H41024241, manufacturer: sui, inc.).

The device comprises: centrifuge (Hunan Instrument centrifuge Co., ltd.), monitor (Jena Ray G3F multifunctional animal monitor, shenen Jena Ray medical instruments Co., ltd.), catalyst One veterinary special full-automatic biochemical analyzer (Edshi), XQ-101 animal blood gas biochemical analyzer (Guangzhou Mo Dekang science and technology Co., ltd.).

The reagents, materials and equipment used in the examples are all commercially available sources unless otherwise specified; the test methods are conventional in the art unless otherwise specified.

Example 1

1. Test animals were prepared.

Preparing a feline test animal: 10 healthy south China tigers (5 each of female and male tigers) are aged 3 years to 12 years and have a weight of about 40 kg to 160 kg.

Preparing a pandas test animal: ma Laixiong 10 (5 male and female animals), 4-12 years old, and about 40-60kg of the weight of the bear.

The feline test animal and the bear test animal are healthy animals which are qualified in quarantine, and each physiological index is normal and the mental condition is good.

Routine examination of the feline and pandas test animals was performed prior to testing, after which the test was performed after ensuring their health. The feline test animals and the bear test animals are respectively fed in the same environment and are fed uniformly. The feline test animals and the bear test animals are fed in the adaptation environment for 1 week and then are subjected to test, and are fasted for 12 hours before the test.

2. Component screening assays for complex anesthetics.

Preparation of a compliance anesthetic for felines and felines.

(1) TMZB group (butorphanol-dexmedetomidine-telitamine-zolazepam group): accurately weighing the required medicament weight of 0.01mg/kg of dexmedetomidine, 0.25mg/kg of telapraximine, 0.25mg/kg of zolazepam and 0.01mg/kg of butorphanol according to the body weight of the test animal, mixing the medicaments, putting the mixture into a 10ml or 20m1 ampoule with good sterilization tightness, adding 10ml of sterilization injection water, uniformly mixing, and visually checking to obtain undissolved powder.

(2) TMZ group (dexmedetomidine-telithamine-zolazepam group): accurately weighing the required medicament weight of 0.02mg/kg of dexmedetomidine, 0.5mg/kg of telapraxine and 0.5mg/kg of zolazepam according to the weight of the test animal, mixing, putting into a 10ml or 20m1 ampoule with good sterilization tightness, adding 10ml of sterilization injection water, uniformly mixing, and visually inspecting to obtain undissolved powder.

(3) TZ group (telitamin-zolazepam group): accurately weighing the required medicament weight of 1mg/kg of telatamine and 1mg/kg of zolazepam according to the body weight of the test animal, placing the test animal into a 10ml or 20ml ampoule with good sterilization tightness, adding 10ml of sterilization injection, uniformly mixing, and visually checking to obtain undissolved powder.

(4) Deer sleep group (dimethylaniline thiazole-dihydro etorphine): accurately extracting 0.03ml/kg of injection of deer hypning according to the body weight of the test animal.

3. Anesthesia test.

The animal training cage is arranged in the first half of the test, and the animal is trained or trained, so that the animal is desensitized to operations such as physical examination, blood sampling and the like of the cage entering and test personnel, and is completely in a freely unstressed state. The test animals were fasted for 12 hours before the anesthesia test, were free to drink water, and were delayed for the test and given in time for the patients with dehydration symptoms. The animals are monitored for various indicators, such as body temperature, blood pressure, heart rate, respiration rate, blood oxygen saturation, and recorded as base values as they adapt to the environment and operation and are in a resting state. Weighing after measuring the basic value, calculating the dosage according to the weight, pumping the liquid medicine into the same syringe, and carrying out intramuscular injection on the shoulder blade part or the forearm part of the test animal according to groups, wherein the dosage of TMZB group, TMZ group and TZ group is calculated according to the dosage of terbutamine: TMZB group 0.20-0.30mg/kg, TMZ group 0.25-0.40mg/kg, TZ group 0.50-1.0mg/kg; the deer sleep-inducing agent is administered at a concentration of 0.027ml/kg to induce general anesthesia.

Starting timing after the injection is finished, taking the injection end until the test animal falls down as an anesthesia induction period, and recording the induction time; recording the time of turning, standing and walking recovery when the anesthesia is revived, taking the standing and walking of the test animal as a sign of the end of the anesthesia, and calculating the anesthesia period time. When the animals start to turn over, the TMZB test group starts to intramuscular injection of the atimetazole hydrochloride according to the weight of the test animal by 0.01mg/kg, the TMZ group starts to intramuscular injection of the atimetazole hydrochloride according to the weight of the test animal by 0.02mg/kg, the TZ group starts to intramuscular injection of the same dose of water (without antagonist) into the TMZ group according to the weight of the test animal, and the deer sleeping group starts to intramuscular injection of deer wake-up agent (the main component is respiratory stimulant nikometer) according to the weight of the test animal by 0.045 ml/kg.

The test animals were allowed to acclimate for 10-30min in the training cage prior to each test, and the test was started after confirming that the animals were unstressed. Immediately after administration, the monitor leads are connected. The multiparameter monitor was turned on 30min before the test to stabilize the instrument performance. The room temperature was maintained at 27 c and the test site was connected to a power on thermostat mode to maintain the body temperature of the test animal.

The test animals were anesthetized with each group of 10 drugs, and the analgesic, sedative and muscle relaxant effects were observed and scored on the following table.

Table 1 test animal sedation effect score

Table 2 test animal analgesic efficacy description and scoring

TABLE 3 test animal muscle relaxant Effect description and scoring

TABLE 4 awakening Effect and scoring

4. Test results.

(1) Anesthesia scoring.

(1) The test results of the analgesic effect are shown in the following table, the test animals are south China tiger and Ma Laixiong, 2 animals are subjected to general anesthesia by using TMZB, TMZ, TZ medicines and other medicines of the deer-sleep-inducing group, the test animals enter an anesthetic state within 5-20min, the analgesic effect of the test animals is slightly different within 0-20min after the test animals enter the anesthetic state, but the TMZB group and the TMZ group basically have full scores, the TZ group has slightly lower analgesic scores, the deer-sleep-inducing group has the lowest score and is maintained at about 2 minutes, and the pain-relieving effect is barely up to the surgical anesthesia standard; within 20-30min, there was a difference in scoring values for each group, wherein there was a significant difference (p < 0.05) between the TMZB group and the TMZ group compared to the deer sleep group, respectively; the analgesic effect among groups is different when the south China tiger and Ma Laixiong are anesthetized by TMZB, TMZ, TZ and other deer sleeping drugs respectively within 30-50 min, wherein the difference between the TMZB group and the deer sleeping drugs is obvious (p < 0.05), and the difference between the other groups is not obvious (p > 0.05); after 50min, the analgesic effect of all the drug combinations starts to decline no matter the south China tiger or Ma Laixiong, and when the drugs of the TMZB group, the TMZ group, the TZ group and the deer sleep group are anesthetized no matter the south China tiger or Ma Laixiong in 50min-90min, the analgesic effect among the groups has obvious difference (p < 0.05); there was also a significant difference (p < 0.05) between the TMZ group and the TZ group; within 90min-120min, the analgesic effect of the drug is also significantly different (p < 0.05) compared with TMZ group, TZ group and deer sleep group.

Table 5 results of the anesthesia and analgesia scores of the south China tiger (x±sd, n=10) for different drug ratios

Table 6 results of different drug ratios Ma Laixiong anesthesia analgesia scores (x±sd, n=10)

Time (min)

0

10

20

30

50

90

120

TMZB group

2.88±0.32

2.90±0.24

2.93±0.07

2.94±0.07

2.88±0.24

2.63±0.88*

1.88±1.32*

TMZ group

2.79±1.36

2.81±0.27

2.86±1..34

2.74±0.28

2.26±1.28

1.57±1.69

1.13±1.21

TZ group

2.51±1.42

2.52±0.37

2.78±1.02

2.12±0.36

2.33±0.78

1.02±0.42

0.87±0.65

Deer sleep-relieving group

2.55±1.05

2.69±0.55

2.66±1.22

2.75±0.33

2.32±0.55

1.45±1.23

1.02±0.89

Note that: * Expressed as comparison of different time points within the group with the basal value, from 0min, the difference was significant (p < 0.05) for both TMZB, TMZ groups compared to the basal value group; at the same time point, comparisons between groups, markers indicate significant differences (p < 0.05).

(2) The test results of the sedative effect are shown in the following table, wherein the test animals are southern tigers and Ma Laixiong, 2 animals are subjected to general anesthesia by using TMZB, TMZ, TZ and deer-sleep-level medicines respectively, the test animals enter an anesthetic state within 5-20min, the sedative effect of the test animals is different within 0-30min after the test animals enter the anesthetic state, and the TMZB is obviously different from the TZ and deer-sleep-level medicines respectively (p < 0.05); when the south China tiger and Ma Laixiong are anesthetized by TMZB, TMZ, TZ and deer sleeping peaceful medicines respectively in 30-50 min, the sedative effect among groups is different, wherein the TMZB group is obviously different from the TZ group and the deer sleeping peaceful group respectively (p < 0.05), and the difference among the other groups is not obvious (p > 0.05); after 50min, the sedative effect of all the drug combinations starts to decline, no matter the sedative effect of the south China tiger or Ma Laixiong, and when 50min-90min, no matter the sedative effect of the south China tiger or Ma Laixiong, the sedative effect of the TMZB group is obviously different (p < 0.05) from the sedative effect of the TMZ group, the TZ group and the deer sleep group respectively compared with the drug anesthesia effect of the TMZ group, the TZ group and the deer sleep group, and the rest differences are not obvious (p > 0.05); within 90-120min, when the TMZB group is compared with the drug anesthesia effects of TMZ group, TZ group and deer sleep group respectively, the sedation effect among the groups is obviously different (p < 0.05), and the difference among the other groups is not obvious (p > 0.05).

Table 7 results of tiger anesthesia sedation scores for different drug ratios (x±sd, n=10)

Table 8 results of sedation scores for different drug ratios maleic Xiong Mazui (x±sd, n=10)

Note that: comparison of different time points within the group, expressed as difference significance (p < 0.05), the two groups of values were compared to the base value, respectively, difference significance p < 0.05).

(3) The test results of the muscle relaxing effect are shown in the following table, wherein the test animals are south China tiger and Ma Laixiong, the three animals are subjected to general anesthesia by using TMZB, TMZ, TZ and deer sleeping-ning medicines respectively, the test animals enter an anesthetic state within 5-20min, after the test animal group enters the anesthetic state, the muscle relaxing effect is slightly different within 0-30min, TMZB is slightly better than TMZ and deer sleeping-ning groups but the difference is not obvious (p is more than 0.05), the muscle relaxing effect of the TZ group is poorer than that of the TMZB group and TMZ group respectively, and the difference is obvious (p is less than 0.05); when the south China tiger and Ma Laixiong are anesthetized by TMZB, TMZ, TZ and other medicines in the deer-sleep-inducing groups within 30-50 min, the muscle relaxing effect among the TMZB, TMZ and deer-sleep-inducing groups is different but not obvious (p > 0.05), and the muscle relaxing effect of the TZ group is poorer than that of the TMZB and TMZ groups respectively, and has obvious difference (p < 0.05); after 50min, the muscle relaxing effect of the medicines of the south China tiger, ma Laixiong, TMZB, TMZ, TZ and deer sleeping peaceful groups starts to be reduced, and when the medicines of the south China tiger, ma Laixiong and the medicines of the TMZB group, the TMZ group and the deer sleeping peaceful groups are anesthetized, the muscle relaxing effect of the TMZB group is better, and the muscle relaxing effect among the groups is obviously different (p < 0.05); compared with TMZ group, TZ group and deer sleep group, TMZB group and TMZ group within 90-120min has better muscle relaxing effect, and has obvious difference (p < 0.05).

Table 9 results of tiger anesthesia muscular relaxation scores (x±sd, n=10) for different drug ratios

Note that: comparison of different time points within the group, expressed as significant difference (p < 0.05)

Table 10 results of scoring for muscle relaxation (x±sd, n=10) for different drug ratios of maleic Xiong Mazui

(2) Recovery state scoring results during the awake period.

The test results are shown in the following table, the test animals are south China tiger and Ma Laixiong, the test animals of TMZB and TMZ groups basically recover completely within 10-90min, and after 120min, the test animals can be conscious and completely awake, and can walk and drink water; the test animals of TZ and deer sleep-improving groups have extremely poor awakening effect. Compared with the results of TMZB group and TMZ group, the difference between 10-50min is extremely remarkable (p < 0.01), mainly the Ma Laixiong of TMZB group and the TMZB group can stand after turning over for 1-3 times during waking up, and the phenomenon of slight ataxia with unstable gait is caused; however, ma Laixiong of TMZ group and south China tiger can stand after 3-8 times of turning over during waking up, and then the phenomenon of serious ataxia such as untidy gait, involuntary wall collision, falling, shaking head and the like is shown. After the test animal group enters the awake state, the ataxia phenomenon of the TMZB group completely disappears within 90-120min, and the ataxia phenomenon of the TMZ group still exists, but the difference between the two is not obvious (p > 0.05). After 120min, animals of each group were fully awakened except for the deer-horn group, the behavior was consistent with that before anesthesia, and there was no phenomenon of repeated entry into the anesthetic state, but the deer-horn group was either an anesthetized Malayan bear or a North China tiger, and the state of repeated entry into the anesthetic-induced state was all present within 1-3 days, and the difference was extremely remarkable (p < 0.01) compared with the other groups.

Table 11 different drug ratios tiger wakeup scoring results (x±sd, n=10)

Note that: comparison of different time points within the group, expressed as significant difference (p < 0.05), expressed as significant difference (p < 0.01)

Is expressed as significant difference (p < 0.05)

Table 12 different drug ratios Ma Laixiong wakeup score results (x±sd, n=10)

Time (min)

0

10

20

30

50

90

120

TMZB group

0.00±0.00

2.90±0.24*

2.76±0.07*

2.82±0.16*

2.82±0.27

2.92±0.0.52

3.00±0.00

TMZ group

0.00±0.00

0.52±0.58

1.21±1.28

1.21±0.74

2.21±1.07

2.68±0.37

3.00±0.00

TM group

0.00±0.00

0.41±0.36

0.20±0.15

0.25±0.22

0.31±0.24

0.86±0.35

1.76±0.62

Deer sleep-relieving group

0.00±0.0

0.33±0.23

0.38±0.21

0.55±0.23

0.72±0.56

0.89±0.68

1.56±0.58

(3) Effects of anesthesia on physiological functions of hua and Ma Laixiong.

The physiological indexes of the hua nan tiger and Ma Laixiong in a calm state before anesthesia are taken as basic values. After administration, the south China tiger and the bear are kept in a supine position or a lateral position, and the probes of the monitor are connected to all parts of the animal body as required. The following parameters were monitored separately.

Respiratory Rate (RR): and monitoring the abdominal wall fluctuation.

Heart Rate (HR): monitoring was performed with a stethoscope.

The body temperature (T) detecting probe is inserted into rectum through anus to be fixed 4-5cm deep.

The blood oxygen saturation probe is clipped onto the tongue so that the infrared is as directed as possible onto the sublingual artery.

The blood pressure cuff of the monitor was placed at the left forelimb elbow joint of the test animal to monitor the mean arterial pressure (Mean arterial pressure, MAP) of the test animal, taking care that the cuff was as high as possible level with the heart.

The change of physiological parameters such as HR, T, RR, sp02 and MAP of Ardisia hupehensis and Mallotus, etc. was recorded at 0min, 10min, 20min, and 30min after administration.

(1) And monitoring the body temperature.

The test results are shown in the following table, after each test group of the hua nan tiger enters an anesthetic state, the body temperature generally shows a descending trend along with the extension of the anesthetic time, and the body temperature respectively drops by 0.6 ℃ and 0.7 ℃ when the anesthetic is performed for 30min, but the body temperature of animals in each test group is within a normal range, and the difference is not obvious (p is more than 0.05); after Ma Laixiong each test group enters an anesthetic state, the body temperature generally decreases along with the extension of the anesthetic time, and the temperature respectively decreases by 0.4 ℃ and 0.3 ℃ when the anesthesia is performed for 30min, but the body temperature of animals in each test group is within a normal range, and the difference is not obvious (p is more than 0.05).

Table 13 comparison of body temperature after anaesthetizing south China tiger (x±sd, n=10) for different drug ratios

Time (min)	0	10	20	30
					TMZB group	39.1±1.3	38.6.±0.7	39.2±0.3	38.9±0.7
TMZ group	39.3±1.2	39.5±1.3	39.4±1.0	39.1±0.9

Table 14 comparison of body temperature of Male bear after anesthesia with different drug ratios (x±sd, n=10)

(2) Respiration rate monitoring results.

The test results are shown in the following table, and after each test group of hua nan tiger enters the anesthesia period, the difference is significant (p < 0.05) when the TMZB group is compared with the TMZ group at 0min, 10min, 20min and 30min, wherein the difference is significant (p < 0.01) when the TMZ group is compared with the basic value, and the difference is not significant (p > 0.05) when the TMZB group is compared with the basic value although the TMZB group is also reduced. After each experimental group Ma Laixiong entered the anesthesia period, the difference was significant (p < 0.05) at 0min, 10min, 20min, 30min compared to the TMZ group, where the difference was significant (p < 0.05) compared to the basal value for the TMZ group, whereas the difference was insignificant (p > 0.05) compared to the basal value for the TMZB group, although there was a decrease in the TMZB group.

Table 15 comparison of respiratory times of hua nan tiger after anesthesia with different drug ratios (x±sd, n=10)

Table 16 comparison of the breathing times Ma Laixiong after anesthesia for different drug ratios (x±sd, n=10)

Time (min)	0	10	20	30
					TMZB group	12.5±3.8*	11.8±3.7*	13.2±4.3*	11.6±5.2*
TMZ group	8.3±2.7	7.6±2.7	5.8±3.2	6.8±2.7

(3) Heart rate monitoring results.

Table 17 comparison of heart rates of hua nan tiger after anesthesia of different drug formulations (x±sd, n=10)

Table 18 comparison of Ma Laixiong heart rate after anesthesia for different drug ratios (x±sd, n=10)

(4) Blood oxygen saturation monitoring results.

Table 19 comparison of blood oxygen saturation of hua nan tiger after anesthesia with different drug ratios (%, x±sd, n=10)

Table 20 comparison of oxygen saturation of maleic Xiong Xie after anaesthesia (in%) for different drug ratios, x±sd, n=10

(5) And (5) monitoring the mean arterial pressure.

The test results are shown in the following table, and after each test group of the hua nan tiger enters an anesthetic state, the difference between the TMZB group and the TMZ group is not obvious (p is more than 0.05) at 0min, 10min, 20min and 30 min. However, the body temperature of the animals in each test group is within the normal range, and the difference is not obvious (p is more than 0.05); after each test group Ma Laixiong enters an anesthetic state, the difference between the TMZB group and the TMZ group is not obvious (p is more than 0.05) at 0min, 10min, 20min and 30 min. However, the body temperature of the animals in each test group was within the normal range, and the difference was not significant (p > 0.05).

Table 21 comparison of mean arterial pressure after anaesthetizing south China tiger (x±sd, n=10) for different drug ratios

Time (min)	0	10	20	30
					TMZB group	158.6±21.7	149.5±18.1	156.5±23.8	151,8±17.2
TMZ group	149.8±38.6	137.4±22.8	151.6±12.2	146.9±16.2

Table 22 comparison of Ma Laixiong mean arterial pressure after anesthesia for different drug ratios (x±sd, n=10)

(4) Comparative analysis of the effect of anesthesia on the circulatory system.

TMZB and TMZ are respectively injected into the muscle of the south China tiger and the muscle of the maleic Xiong Beibu, and when the temperature of the muscle is 0min, 10min, 20min and 30min, the TMZB group and the TMZ group have obvious effects on the heart rate and the blood oxygen saturation degree, and the difference of the mean arterial pressure is not obvious. The result shows that TMZ group has a certain influence on the circulatory system of the south China tiger by inhibiting the heart rate, but the condition of inhibiting the heart rate of TMZB group is obviously improved and the difference from the basic value is not obvious. The results of the comparative analysis of each test group Ma Laixiong were similar to those of each test group of south China tiger.

(5) Comparative analysis of the effect of anesthesia on the respiratory system.

After two groups of compound anesthetic are respectively injected into each test group of the south China tiger and the bear, the two groups are compared, the TMZB group has no obvious inhibition on breathing, the breathing is uniform, the breathing frequency and the basic value are not greatly different, the time between the breathing intervals is shorter, the blood oxygen saturation is about 90%, and the oxygen supply and the oxygen consumption of the organism are basically balanced, so that the anesthesia state is better. The TMZ group has a certain inhibition effect on the respiratory system, is obviously different from the basic value group, is characterized in that the respiratory interval is longer, the respiratory superficial is formed, the respiratory times per minute are obviously reduced, and the blood oxygen saturation is about 70-80%, so that the oxygen supply and the oxygen consumption of the organism are in an unbalanced state, the organism has a certain degree of hypoxia, and the life of tigers and bear can be endangered when serious. The TMZ group shows slight to moderate inhibition on the respiration of the south China tiger and the bear, which indicates that the dexmedetomidine in the mixture has certain respiratory inhibition, the analgesic and sedative effects of the butofil lighten the dosage of the dexmedetomidine, and lighten the inhibition on the respiration and circulatory system of the dexmedetomidine.

The TMZB group can use the atemezole hydrochloride in the awakening process, the medicine can be used for emergent awakening when accidents occur in the anesthetic process, the medicine is an antagonist of dexmedetomidine, the inhibiting effect of dexmedetomidine on respiratory and circulatory systems can be quickly reversed, in the use process, the score of the awakening period of the TMZB group is obviously higher than that of the TMZ group, the ataxia and mania behaviors are obviously weakened, the awakening is stable and rapid, the main reason is that the use amount of the temitamine and the zolazepam is reduced due to the addition of the butocofenol, and the larger the use dose of the latter two medicines is when animals awaken, the more obvious the ataxia and mania phenomenon is caused.

In the anesthesia process, the monitoring of the blood oxygen saturation can directly reflect the oxygenation state of an animal body, can evaluate the inhibition degree of the medicine on respiratory, cardiovascular and central nervous systems, and can provide timely and effective diagnosis basis for the occurrence of hypoxia. In the comparative experiments carried out on the two groups, the blood oxygen saturation of the TMZ group is reduced to a certain extent after administration, and additional oxygen supply is needed, while the blood oxygen saturation of the TMZB group is always maintained above 90% in the whole anesthesia process, which indicates that the inhibition degree of the TMZB group on respiration is slight, the occurrence of hypoxia is avoided, and the anesthesia monitoring is finished and the operation is restored to normal.

Through the comparative analysis, the compound preparation (TMZB) of the british and the dexmedetomidine and the tibetamine and the tazobactam and The Mixture (TMZ) of the dexmedetomidine and the tibetamine and the tazobactam are obtained, the difference of the respiratory and heartbeat inhibition degree of the hua nan tiger and the Malus bearberry is obvious (p is less than 0.05), the respiratory and heart rate of the hunan tiger and the Malus bearberry injected with the TMZB has no obvious inhibition effect, and the effects of myopine, sedation and analgesia are obvious and are obviously superior to those of the TMZ group. As for the commonly used deer hyping and compound ketamine mixture, the main components are tranquilizer and selazine respectively, and the two components are nonselective alpha 2-adrenoceptor agonists, so that the problems of no antagonist, poor pain relieving and muscle relaxing, easiness in repeated entry into induced anesthesia state and the like exist. TMZB effectively improves the defects of the medicines, and is an ideal composite anesthetic for felines and bear animals.

The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.

The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims

1. The application of a compound anesthetic in preparing a preparation for general anesthesia of large-sized felines or felines is characterized in that the compound anesthetic comprises an anesthetic component and a wake-up component;

the large feline is: hua nan hu; the pandas are: ma Laixiong;

the anesthetic component comprises the following raw materials in parts by weight:

dexmedetomidine 1 part

25 parts of telitamin

Zolazepam 25 parts

1 part of butorphanol;

the anesthetic ingredient is administered at a dose of 0.40-0.65mg/kg body weight;

the waking ingredient is atemezole, administered at a dose of 0.01mg/kg body weight.

2. The use according to claim 1, characterized in that the use comprises intramuscular injection and/or intravenous injection.