Safety inspection of traditional Chinese medicine injections (3)

4.

(1) The rabbits are healthy and non-injured, weighing more than 1.

(2) New rabbit preselection

1) After the new rabbits have been raised for 7 days, the body temperature is predicted, and the temperature measurement conditions are the same as the pyrogen inspection requirements

2) When measuring body temperature, the depth of the thermometer probe or anus meter inserted into the anus should be about 6cm the same for each rabbit, and the temperature measurement time should not be less than 1.

3) The temperature is measured once every 30 minutes, a total of 8 times

4) Rabbits whose body temperature is within the range of 38.

5) Record the new rabbit number and register in the rabbit history record card.

(3) Repeated use of domestic rabbits

1) The test product is judged to be a domestic rabbit that meets the requirements, and it should be rested for at least 2 days before it can be used in the next experiment

2) The test product is judged to be a rabbit that needs to be repeated, and it should be temporarily rested.

3) Rabbits that are judged to be non-compliant with the test product are no longer used

4) The number of times of use of each rabbit is recommended to be at most 10 times.

5) Rabbits used for the detection of blood products, antitoxins and other test substances with the same antigenicity can be used repeatedly once within 5 days

(4) Re-test rabbits: select rabbits with a body weight of 2.

5.

(1) Thermometer or anal thermometer: Check once every 3-6 months.

(2) Depyrogenation of utensils: put cleaned glassware, syringes, needles, straight tweezers, etc.

(3) The rabbits should stop feeding at least 1 hour before the test and place them in a loose and suitable rabbit fixed box.
During the test, the animals should be prevented from agitating and attention should be paid to avoid noise interference
.

(4) The temperature of the laboratory

1) The temperature of the laboratory should be within the range of 17～25℃
.

2) The temperature difference between the laboratory and the breeding room shall not exceed 3°C
.

3) During the whole test, the room temperature should not change more than 3℃
.

6.
Inspection method

(1) Choose a rabbit that meets the requirements, stop feeding and water, weigh it and place it in the rabbit fixed box for at least 1 hour
.

(2) Measure the rabbit's body temperature once every 30 minutes, generally twice, and the difference between the two body temperatures should not exceed 0.
2°C, and the average of the two body temperatures is taken as the rabbit's normal body temperature
.

(3) The normal body temperature of the rabbits used on that day should be within the range of 38.
0～39.
6℃, and the difference between rabbits should not exceed 1℃
.

(4) Use 3 rabbits for each test sample, and administer within 15 minutes after measuring normal body temperature
.

1) The dose of the test product should be injected according to the regulations under each drug item.
For drugs with unspecified doses, the pharmacological properties of the drug can be calculated on the basis of body weight without affecting the normal physiology of the rabbit.
Calculate), use 3 to 10 times the clinical dose
.

2) The injection volume of the test product shall be no less than 1ml and no more than 10ml per kg of rabbit body weight
.
A solution with a volume of 6-10ml/kg should be injected after preheating to about 38°C
.

3) After the preparation of the test product is completed, it should be injected into the rabbit within 30 minutes
.

4) Before injection, use a 76% ethanol cotton ball to gently wipe the injection site of the ear vein, and insert the needle from the tip of the ear.
If the needle is unfavorable, proceed forward in order
.

5) After the injection is completed, when the needle is pulled out, press and hold the needle hole for a few seconds to stop the bleeding
.

6) For drugs that require slow injection, the injection time (unless otherwise specified) generally does not exceed 6 minutes per rabbit
.

(5) Measure body temperature every 30 minutes after administration, 6 times in total
.

(6) Temperature difference calculation

1) After injecting the liquid medicine, subtract the normal body temperature from the highest one of the 6 measured body temperatures, which is the raised temperature of the rabbit's body temperature.
If the body temperature of the 6 times is lower than the normal body temperature, the body temperature rise value is "0" Count
.

2) The lowest one of the 6 body temperatures, minus the normal body temperature, is the cooling value
.

7.
Result judgment

(1) It is determined that only one of the 3 rabbits in the first retest has a temperature rise of 0.
6°C or more, or the temperature rise of all 3 rabbits is lower than 0.
6°C but the sum of the temperature rises reaches 1.
3°C or more.
Take 5 rabbits for re-examination
.

(2) Judged as qualified

1) In the initial test of 3 rabbits, the body temperature rise is lower than 0.
6℃, and the total temperature rise of the 3 rabbits is lower than 1.
3℃, which can be judged to meet the requirements:

2) Among the 5 rabbits in the re-test, the number of rabbits whose body temperature increased by 0.
6°C or above is not more than 1, and the combined initial re-test, the total temperature of the 8 rabbits is 3.
5°C or lower than 3.
5°C, which can be judged To comply with regulations
.

(3) Determined as unqualified

1) Among the 3 rabbits in the initial test, there are 2 or 3 rabbits whose body temperature rises by 0.
6℃ or above, which can be judged as non-compliant
.

2) Among the 5 rabbits in the retest, more than 1 rabbit whose body temperature has risen by 0.
6°C or above can be judged as non-compliance
.

3) In the initial retest, the total temperature rise of 8 rabbits exceeds 3.
5℃, which can be judged as non-compliance
.