JP-7854742-B2 - Microparticles containing moxidectin and sustained-release injectable composition containing the same

Inventors

• キム ジュヒ
• イ サンノ

Assignees

• インベンテージ ラボ インコーポレイテッド

Dates

Publication Date

20260507

Application Date

20220427

Priority Date

20220413

Claims (8)

1. These are microparticles containing moxidectin and biodegradable polymers. The intrinsic viscosity of the biodegradable polymer is 0.2 dl/g to 1 dl/g. The average diameter of the aforementioned microparticles is 60 to 110 μm. The biodegradable polymer is selected from the group consisting of polylactide (PLA), polylactide-coglycolide (PLGA), and mixtures thereof. Microparticles containing moxidectin.
2. The microparticles are spherical, The microparticles uniformly contain moxidectin. Microparticles containing moxidectin as described in claim 1.
3. The coefficient of variation (CV) of the aforementioned microparticles is between 5% and 20%. Microparticles containing moxidectin as described in claim 1.
4. The microparticles contain a biodegradable polymer and moxidectin in a weight ratio of 2:1 to 12:1. Microparticles containing moxidectin as described in claim 1.
5. The aforementioned microparticles continuously release moxidectin for more than three months. Microparticles containing moxidectin as described in claim 1.
6. The aforementioned microparticles are 0.3 to 3 according to the following formula 1. Microparticles containing moxidectin as described in claim 1: [Formula 1] C max-peak n /C max-peak n+1 Here, Microparticles containing moxidectin were mixed with a suspension solution to prepare an injectable preparation, and the injectable preparation was administered to beagle dogs, and the blood concentration of moxidectin was measured. C max-peak n is the nth Cmax value after the injection of the drug. C max-peak n+1 is the (n+1)th C max value resulting from the increase in moxidectin blood concentration again after the nth C max value.
7. Multiple beagle dogs were administered 0.2 mg/kg of moxidectin as the aforementioned injectable agent, and the blood concentration of moxidectin was measured. The standard deviation of blood moxidectin concentration among beagle dogs administered the aforementioned injectable agent is 0.01 to 10. Microparticles containing moxidectin as described in claim 6 .
8. Microparticles containing moxidectin as described in claim 1, Includes a suspension solution, A sustained-release injectable composition containing moxidectin.

Description

This invention relates to microparticles containing moxidectin and sustained-release injectable compositions containing the same. Heartworm disease (HWD) is caused by a parasite called Dirofilaria immitis, transmitted by mosquitoes, and infects dogs, cats, and weasels. As the name suggests, heartworm parasites infect the hearts of mammals. Adult heartworms (Dirofilaria immitis) can grow up to 30 cm in length and primarily parasitize the pulmonary artery and right ventricle. Mature male and female heartworms produce very small larvae called microfilariae (L1). These larvae parasitize the blood of infected animals and are transmitted to other animals by mosquitoes. L1 larvae become infectious after two weeks in a mosquito's body, and these infectious larvae can then be transmitted to other animals by mosquitoes. The larvae that infect other animals undergo several stages of development and migrate to the pulmonary artery after 3-4 months. Mature adult heartworms live for an average of 5-7 years, and both male and female heartworms reproduce, producing a large number of larvae. The heart and pulmonary arteries of infected animals can be infested with between one and 200 heartworms. Infection causes the pulmonary arteries to thicken and become inflamed, forcing the heart to work harder to pump blood to the lungs while avoiding the worms. Inflammation also occurs in the lungs. While there may be no specific symptoms when the number of infected heartworms is small, animals infected with heartworm generally show initial symptoms such as avoidance of exercise, coughing, and weight loss. In severe cases, symptoms such as severe coughing, difficulty breathing, and heart failure may occur. Animals infected with heartworm may die from heart failure if they exhibit these symptoms. If a diagnosis confirms infection with heartworm, treatment can be carried out using arsenic-based drugs (caprosolate) to kill the adult heartworms, or using melarsomine. However, both of these treatments cause severe irritation at the injection site and have side effects that can cause some degree of damage to the liver and kidneys. Therefore, preventing heartworm infection before it occurs is economical and safe. Prevention should be given between 6 and 8 weeks of age. Heartworm preventatives include diethylcarbamazine (DEC), administered daily, or ivermectin, milbemycin, moxidectin, and selamectin, administered monthly. While all preventatives are highly effective when administered correctly, the need to administer them daily or monthly means that even a few missed doses expose the dog to the risk of infection. Therefore, there is an urgent need to develop a canine heartworm preventative drug that uses moxidectin, which can prevent heartworm infection, and maintains its efficacy for more than three months with a single dose, thereby improving the convenience of administration. Korean Published Patent No. 10-2006-0005472 These are experimental results regarding the moxidectin release pattern of microparticles according to one embodiment of the present invention.This is an experimental result regarding the moxidectin release pattern of microparticles according to one embodiment of the present invention.These are experimental results regarding the moxidectin release pattern of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This is a SEM measurement image of microparticles according to one embodiment of the present invention.This shows the results regarding the blood moxidectin concentration measured after adm