Toxicokinetics
The absorption, distribution and metabolism of chlorpheniramine were evaluated in male SD rats and Beagle dogs. The results of the toxicological and kinetic oral absorption study showed that chlorophenylglyceride would be rapidly absorbed and then discharged mainly through urine. The final components of urine include 3-P-chlorophenoxylactic acid, pchlorophenoxylic acid and chlorophenylglyceride. The study of subcutaneous absorption shows that chlorophenylene glycol can be absorbed into the body through the skin, up to 57% of which can be absorbed, and then these absorbed amounts will be completely excreted after 96 hours.
toxicology
A. Acute oral toxicity
Through the acute toxicity test of Iq administration in rats, the LD50 of chlorpheniramine was 3000 mg/kg. This test showed that the group with the largest dose of chlorphenidate (1:3) repeatedly administered to rats had significant weight loss and low hemoglobin (1000mg/kg/day). This group also reported a decrease in the weight of the spleen and thymus. In the study, the only microscopic finding related to treatment was that in the highest dose group, a male rat had renal tubule expansion/necrosis. In the 100mg/kg/day dose group, it was observed that the appearance was bright and the saliva secretion was also increased. No adverse effects were found in the study in the 10 mg/kg/day group.
B Irritation
Three New Zealand albino rabbits were used to evaluate the eye irritation potential of oxyphenidate; Six male New Zealand albino rabbits were used to evaluate the skin irritation of chlorpheniramine; Taking human as the experimental object, the skin pricking property of chlorpheniramine was determined by 24-hour closed patch test and sensory stimulation test; Taking guinea pigs as experimental objects, a test was conducted to determine the maximum non irritating concentration of chlorophenylene glycol; Human subjects were used to test the irritation of different concentrations of chlorophenylglyceride by repeated patch test (HRIPT).
When oxyphenylglyceride was infused into the eyes of rabbits at a concentration of 1%, it was found that there was slight irritation to the eyes. The experiment was also conducted with rabbits. After 24 hours in a closed place, the same test concentration was applied to the skin, without skin irritation. The human closed patch test showed that after applying 0.3% chlorophenylglycerol ether and waiting for 48 hours, there would be negligible skin irritation. The Committee considered studying the increase in reports of sensory stimulation potential of some face cream added with chlorophenylglycerol ether, especially when used together with p-hydroxybenzoate+phenoxyethanol. The Commission assessed the potential for such sensory stimulation, and sensory stimulation was tested in 16 healthy volunteers, with formulations containing methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, and chlorophenylglycerol (0.4%, 0.5% aqueous solution of carboxy vinyl polymer), compared with the same formulation of isochlorophenylglyceride. It is the most exciting. The facial sensory stimulation test was originally proposed by Frosch and Kligman. In the previous evaluation of CIR safety OC monohydroxy acids (AHAs), it was concluded that the sensory stimulation in the sensitive area of the tissues around the eyes was such that the use of products containing AHA formula near the eyes would reduce stinging and burning reactions. Fruit acid has also been shown to be irritating to the skin. In the guinea pig experiment, when the concentration of chlorophenylglyceride was 0.5% or 1%, it did not cause anaphylaxis, and these two concentrations were used as the initial concentration of stimulation. 0 (monohydroxy acid (AHA) component, also known as skin irritant, but chlorophenylglyceride is not. At present, the concern about sensory stimulation is more about baby products, such as diaper cream. Chlorophenylglyceride, however, has not been reported for use in baby products.
According to the results of repeated patch tests, for healthy people, test materials containing 12% - 17% chlorophenylglyceride will cause clinically insignificant erythema, and no signs of skin allergy are found on any tester; The test material containing 5%~9% chlorophenylglyceride will not cause skin irritation and allergy. When 11 patients with photoallergy were tested with ketoprofen and chlorophenylglyceride, the results were negative. For people with allergic constitution, it is found that 0.5% and 1% of chlorophenylglyceride may have positive allergic reaction
C immunosuppression
With white rabbits as experimental objects, the immunosuppressive activity of oxyphenidate was evaluated. In the test with a concentration of 1 or 10mg/ml, it was observed that it significantly inhibited the reaction of CA (+) hemagglutinin, but low concentrations, such as 0.01 or 0.1 mg/ml, did not produce this inhibition reaction. Chlorophenidate was not very effective in inhibiting the formation of antibodies when there were a large number of antigens. In the case of a small amount of antigen, CPG can partially inhibit the antibody reaction. Through a variety of in vitro tests, the results of human and mouse cellular immune test systems show that it has an inhibitory effect on a wide range of lymphocytes B and T, mainly inhibiting the proliferation reaction, and can reduce the development of immune cell cloning in vivo in these cells. By studying the effect of chlorpheniramine on the immune response of mice, rabbits and guinea pigs, chlorpheniramine is an effective immunosuppressive agent, because it is an immunosuppressive agent acting with antigen, and it will not affect the level of existing antibodies or duplicate effects, nor increase the risk of animal infection