The development prospect of avermectins
Avermectins has excellent repelling and killing efficacy on endoparasite and ectoparasite as well as unique parasite resistance mechanism. A large number of clinical applications in China have proved that avermectins is safe and efficient, which cannot be replaced by other drugs in controlling ectoparasite of arthropods. Our company put a lot of energy in the extensive research on the preparation technology of avermectins. Below are some views on the development prospect of avermectins.
It is well-known that avermectins is a kind of macrolide antibiotics, besides, it is very difficult to store as it is easy to resolve under light and is quite unstable. Even the standard abamectin insecticide products often tend to be nonstandard. Merck & Co Inc in America can be the earliest company that carried out the laboratory study and began the industrial production of avermectins in the world, but they did not launch abamectin. On the contrary, they pushed ivermectin, a kind of abamectin -C22-C23-selective reduction product to the market due to the instability of abamectin. Soon afterwards, Pfizer Inc. in America also launched doramectin (dectomax), one of abamectin semisynthetic products, which connects six-membered ring on abamectin C25. Compared with abamectin, semisynthetic avermectins is more stable and has lower toxicity. In terms of pharmacokinetics, although it has high plasma concentration peak value and long duration of effective drug concentration, it is almost same with abamectin that has no breakthrough in the insecticidal spectrum.
For the consideration of semisynthetic abamectins price and synthetic technique, China vigorously promoted abamectin from the beginning but did not find its instability until it is applied in the clinical practice. We can predict that in the future, abamectin should be replaced by the semisynthetic products of avermectins, of which the production cost should be reduced firstly.
a. Expand the insecticidal spectrum: due to the limitation of parasite resistance mechanism, avermectins can only have killing effect on vivo nematode and vitro arthropda parasite, but has no killing effect on fluke and tapeworm, which can be killed by albendazole and praziquantel. Therefore, by producing propylene mixture and pyrazole mixture, which can help to expand the insecticidal spectrum, reduce the drug using frequency and bring convenience for the users. However, regarding the practical application of these kinds of compound preparations, pharmacokinetics should be studied so as to confirm the optimal dosage regimen of the compound medicine.
b. Strengthen the quality control: the raw materials and solvent (such as propylene glycol) of abamectin preparations that contain some impurities will influence the transparency of injection and increase the adverse reaction after injecting, therefore, the quality of raw material should be controlled strictly, which can be filtered by microporous membrane.
c. Reduce pain reaction: the stress that occurred in the pain reaction after injecting is much greater than the stress that occurred in weighing, herd transferring and immunization, which is quite harmful for the livestock. Therefore, it is necessary to add ancillary drug so as to reduce pain reaction, thus it will be convenient for muscle administration and can be easy to use.
d. The stability and biological availability of preparations: in order to ensure the stability and efficiency of preparations, the stabilizer (antioxidant) can be added. Enteric coatel tablets, one of avermectins products, can effectively reduce the damage caused by ruminant rumen microorganism and improve the biological availability. In addition, the microcapsule of avermectins can not only keep stability, but also can extend the curative effect and reduce toxicity, which can be regarded as an effective improvement way for the promotion of abamectin pesticide.
e. Sustained and controlled release technology: the general preparations is often injected in the impulse type, thus the drug will fluctuate intensively in blood and tissue, besides, the duration of effective drug concentration will be short. Therefore, it can be entirely possible to extend the duration of effective drug concentration by using new type of ancillary drug, of which the ultimate goal is to reduce administration frequency and improve killing and repelling effect.