Microparticles containing moxidectin and methods for preparing the same

Abstract

The present invention discloses a moxidectin-containing microparticle, comprising moxidectin and a biodegradable polymer, wherein the microparticle is in the form of spherical biodegradable polymer microparticles in which the moxidectin drug is uniformly distributed, and the average particle size of the microparticle is 80 to 130 μm. The present invention relates to a sustained-release microparticle and a preparation method thereof, wherein the microparticle containing moxidectin can maintain a continuous effect of preventing heartworms for 3 to 6 months by administering the microparticle, and in addition, the present invention makes the average diameter of the particles into a certain micro-size, thereby reducing the foreign body sensation and pain when administering the injection to animals, making the administration of the injection easy.

Description

Technical Field

[0001] The present invention relates to a microparticle containing moxidectin and a preparation method thereof, and more particularly to a microparticle containing moxidectin and a biodegradable polymer capable of preventing heartworms and a preparation method thereof. Background Art

[0002] Heartworm Disease (HWD) is a mosquito-borne parasite called Dirofilaria immitis that infects dogs, cats, and weasels. As the name suggests, heartworms live in the hearts of mammals.

[0003] Adult heartworms can grow up to 30cm and mainly parasitize in the pulmonary artery and right ventricle. Mature female and male heartworms produce very small larvae called microfilariae (L1). These larvae parasitize in the blood of infected animals and infect other animals through mosquitoes. L1 that enters the mosquito's body will become infectious after two weeks, and the infectious larvae will be transmitted to other animals again through mosquitoes. The larvae that infect other animals migrate to the pulmonary artery after several growth stages over 3 to 4 months. These mature adult heartworms live an average of 5 to 7 years, and female and male heartworms produce many larvae through reproduction.

[0004] An infected animal can have as few as one to as many as 200 heartworms living in the heart and pulmonary arteries. The infection causes the pulmonary arteries to thicken and become inflamed, requiring the heart to work harder to keep the worms away and supply blood to the lungs. In addition, the lungs may become inflamed. When the number of heartworms infected is small, there are no specific symptoms, but animals with heartworm infections may show early signs such as fearful movements, coughing, and weight loss. In severe infections, severe coughing, difficulty breathing, and heart failure may occur. There are also cases where animals infected with heartworms show these symptoms and die from heart failure.

[0005] When heartworm infection is diagnosed, the adult heartworms can be killed with the drug caparsolate or treated with melarsomine. However, both of these treatments have serious side effects, such as excessive irritation at the injection site and some degree of damage to the liver and kidneys.

[0006] Therefore, prevention before heartworm infection is economical and safe. Prevention is performed at 6 to 8 weeks after birth. Heartworm preventive drugs include diethylcarbamazine (DEC) taken daily or ivermectin, milbemycin, moxidectin, selamectin, etc. taken monthly. When preventive drugs are taken correctly, their preventive effects are excellent, but since they need to be taken every day or every month, there is a possibility of forgetting the number of times to take them, which may lead to exposure to the risk of infection. .

[0007] Therefore, there is an urgent need to develop a heartworm preventive drug that can utilize moxidectin for preventing heartworms and maintain the efficacy for 3 to 6 months through a single administration, thereby improving the convenience of administration.

[0008] Prior art literature

[0009] Patent Literature

[0010] Patent Document 1: KR10-2006-0005472 A1 Summary of the invention

[0011] Problem that the invention aims to solve

[0012] The present invention relates to microparticles containing moxidectin and a preparation method thereof.

[0013] The present invention aims to provide a sustained-release microparticle and a preparation method thereof. Unlike existing heartworm preventive drugs that have a short half-life and need to be administered daily or monthly, microparticles containing moxidectin can maintain a continuous heartworm prevention effect for 3 to 6 months.

[0014] Another object of the present invention is to provide sustained-release particles containing moxidectin, while maintaining a long-term administration effect of 3 to 6 months, to make the average diameter of the particles into a certain micro-size, to control the release of the drug from the particles, to maintain a constant and effective drug concentration, and when applied to injections, it contains particles of uniform size, to reduce foreign body sensation and pain during administration.

[0015] Means used to solve problems

[0016] In order to achieve the above object, as a specific example of the present invention, the present invention relates to a microparticle containing moxidectin, which contains moxidectin and a biodegradable polymer. The microparticle is in the form of spherical biodegradable polymer microparticles in which the moxidectin drug is uniformly distributed, and the average particle size of the microparticle is 80 to 130 μm.

[0017] As a specific example of the present invention, the microparticles of the present invention may contain the biodegradable polymer and moxidectin in a weight ratio of 4:1 to 9:1.

[0018] As a specific example of the present invention, the microparticles of the present invention can continuously release moxidectin for 3 to 6 months.

[0019] As a specific example of the present invention, the biodegradable polymer of the present invention can be selected from the group consisting of polylactic acid, polylactide, polylactide-co-glycolide, polylactic acid-co-glycolic acid (PLGA), polyphosphazene, polyimide carbonate, polyphosphate, polyanhydride, polyorthoester, polycaprolactone, polyhydroxyvalerate, polyhydroxybutyrate, polyamino acid and combinations thereof, and polylactic acid-co-glycolic acid (PLGA) is preferred, but is not limited to the above examples.

[0020] As a specific example of the present invention, the microparticles of the present invention are prepared by using a microchannel, and the ratio of the width w of the cross section of the microchannel to the average diameter d' of the microparticles is in the range of 0.7 to 1.3.

[0021] As a specific example of the present invention, the microparticles of the present invention are prepared by using a microchannel, and the ratio of the height d of the microchannel cross section to the average diameter d' of the microparticles is in the range of 0.7 to 1.3.

[0022] As a specific example of the present invention, it relates to a pharmaceutical composition for preventing and treating heartworms comprising the microparticles according to the present invention.

[0023] As a specific example of the present invention, the present invention relates to a method for preparing microparticles containing moxidectin, comprising: step 1: dissolving a biodegradable polymer and moxidectin in an organic solvent to prepare a first mixture; step 2: dissolving a surfactant in water to prepare a second mixture; step 3: injecting the first mixture of the step 1 into a microchannel in a linear direction to make it flow; step 4: injecting the second mixture of the step 2 into a microchannel formed on both sides or one side so as to form an intersection with the microchannel in the step 3 in which the first mixture flows in a linear direction, and flowing the microchannel, the first mixture flow in the linear direction intersects with the second mixture flow, to prepare microparticles in which moxidectin is uniformly distributed in spherical biodegradable polymer particles; step 5: collecting microparticles generated at the intersection of the step 4; step 6: stirring the microparticles collected in the step 5 to remove the organic solvent present in the microparticles by evaporation; and step 7: washing and drying the microparticles of the step 6; the average particle diameter of the microparticles is 80 to 130 μm.

[0024] As a specific example of the present invention, the first mixture in the first step of the present invention may contain 15 to 60 wt % of biodegradable polymer.

[0025] As a specific example of the present invention, the first mixture of the first step of the present invention may include the biodegradable polymer and moxidectin in a weight ratio of 4:1 to 9:1.

[0026] As a specific example of the present invention, the biodegradable polymer of the present invention can be selected from the group consisting of polylactic acid, polylactide, polylactide-co-glycolide, polylactic acid-co-glycolic acid (PLGA), polyphosphazene, polyimidocarbonate, polyphosphate, polyanhydride, polyorthoester, polycaprolactone, polyhydroxyvalerate, polyhydroxybutyrate, polyamino acid and combinations thereof, and is preferably polylactic acid-co-glycolic acid (PLGA), but is not limited to the above examples.

[0027] As a specific example of the present invention, the organic solvent in the first step of the present invention is at least one selected from the group consisting of dichloromethane, chloroform, ethyl chloride, dichloroethane, trichloroethane and a mixture thereof.

[0028] As a specific example of the present invention, the second mixture in the second step of the present invention may contain 0.2 wt % to 0.3 wt % of a surfactant.

[0029] As a specific example of the present invention, the surfactant in the second step of the present invention is at least one selected from the group consisting of nonionic surfactants, anionic surfactants, cationic surfactants and mixtures thereof.

[0030] As a specific example of the present invention, the third step of the present invention can inject the first mixture into the microchannel in a linear direction at a pressure of 1000 to 1500 mbar.

[0031] As a specific example of the present invention, the fourth step of the present invention injects the second mixture into a microchannel formed on two sides or one side to form an intersection with the microchannel in the linear direction of the first mixture flowing, and the second mixture can be injected at a pressure of 1500 to 2000 mbar.

[0032] As a specific example of the present invention, in the fifth step of the present invention, the microparticles may be collected in a water tank containing a mixed solution containing 0.2 wt % to 0.3 wt % of a surfactant.

[0033] As a specific example of the present invention, the step 6 of the present invention may include: step 6-1, stirring for the first time at a speed of 200 to 400 rpm for 1 to 2 hours at 15 to 20°C; step 6-2, after the first stirring step, stirring for the second time at a speed of 300 to 500 rpm for 1 to 2 hours at 20 to 30°C; and step 6-3, after the second stirring step, stirring for the third time at a speed of 400 to 600 rpm for 3 to 5 hours at 40 to 50°C.

[0034] As a specific example of the present invention, the microchannels of the third and fourth steps of the present invention are formed on the surface of the wafer, and the average diameter of the microchannels is 60 to 150 μm, preferably 80 to 120 μm, and more preferably 100 μm, but is not limited to the example.

[0035] Effects of the Invention

[0036] The present invention relates to a microparticle containing moxidectin and a preparation method thereof, and relates to a sustained-release microparticle and a preparation method thereof. By administering the microparticle containing moxidectin, the effect of continuously preventing heartworms for 3 to 6 months can be maintained.

[0037] In addition, the average diameter of the particles of the present invention is made to maintain a certain micro size, thereby reducing the foreign body sensation and pain when administering the injection to animals, making the administration of the injection easier. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 The present invention is a flow chart of a method for preparing microparticles containing moxidectin.

[0039] Figure 2 It is a curve diagram showing the drug release period according to the weight ratio of the biodegradable polymer and moxidectin according to the present invention.

[0040] Figure 3 It is a curve diagram showing the drug release period according to the weight ratio of the biodegradable polymer and moxidectin according to the present invention.

[0041] Figure 4 is a SEM photograph of microparticles prepared by a method according to an embodiment of the present invention.

[0042] Figure 5 is a SEM photograph of microparticles prepared by a method according to an embodiment of the present invention.

[0043] Figure 6 is a SEM photograph of microparticles prepared by a method according to an embodiment of the present invention.

[0044] Figure 7 is a SEM photograph of microparticles prepared by a method according to an embodiment of the present invention.

[0045] Figure 8 This graph shows the relationship between the average diameter of microparticles and the cross-section of microchannels. DETAILED DESCRIPTION

[0046] The present invention relates to a microparticle containing moxidectin. The microparticle contains moxidectin and a biodegradable polymer. The microparticle is in a state where the moxidectin drug is uniformly distributed in the spherical biodegradable polymer. The average particle diameter of the microparticle is 80 to 130 μm.

[0047] The embodiments of the present invention will be described in detail below so that those skilled in the art can easily implement the present invention. However, the present invention can be implemented in various forms and is not limited to the embodiments described here.

[0048] The moxidectin of the present invention is a compound represented by the following Chemical Formula 1, and is a substance used as a heartworm preventive for animals.

[0049] Chemical formula 1

[0050]

[0051] Figure 1 The present invention is a flow chart of a method for preparing microparticles containing moxidectin.

[0052] According to the flow chart, the preparation of the microparticles containing moxidectin of the present invention is carried out in the following order: Step 1 S100: preparing a first mixture; Step 2 S200: preparing a second mixture; Step 3 S300: injecting the first mixture into a microchannel in a linear direction; Step 4 S400: injecting the second mixture into a microchannel on both sides or one side; Step 5 S500: collecting microparticles; Step 6 S600: stirring the collected microparticles; and Step 7 S700: cleaning and drying the microparticles.

[0053] More specifically, a method for preparing microparticles containing moxidectin according to an embodiment of the present invention is described as follows.

[0054] The first step S100 is a step of preparing a first mixture, which is a step of dissolving a biodegradable polymer and moxidectin in an organic solvent to prepare a first mixture. The biodegradable polymer is selected from the group consisting of polylactic acid, polylactide, polylactide-co-glycolide, polylactic acid-co-glycolic acid (PLGA), polyphosphazene, polyimidocarbonate, polyphosphate, polyanhydride, polyorthoester, polycaprolactone, polyhydroxyvalerate, polyhydroxybutyrate, polyamino acid and a combination thereof, preferably polylactic acid-co-glycolic acid (PLGA), but is not limited to the example.

[0055] In addition, the organic solvent is not miscible with water, for example, any one or more selected from the group consisting of chloroform, ethyl chloride, dichloroethane, trichloroethane and mixtures thereof, preferably dichloromethane, but not limited to the examples. The organic solvent capable of dissolving the biodegradable polymer and moxidectin is not limited to the examples, and any organic solvent that can be easily selected by a person skilled in the art can be used.

[0056] The first step S100 is a step of preparing a first mixture of dissolved biodegradable polymer and moxidectin. As described above, an organic solvent is used as a solvent. It utilizes the solubility characteristics of moxidectin and biodegradable polymer and uses an organic solvent to completely dissolve. After complete dissolution, the first mixture contains biodegradable polymer and moxidectin in a weight ratio of 4:1 to 9:1, preferably 4:1, but not limited to the example. When the weight ratio of biodegradable polymer and moxidectin is less than 4:1, that is, when the biodegradable polymer is contained in a manner less than the above weight ratio, the weight ratio of the biodegradable polymer is lower than the weight of moxidectin, and it is difficult to prepare microparticles in which the moxidectin drug is uniformly distributed and contained in the form of spherical biodegradable polymer particles. When the weight ratio of biodegradable polymer and moxidectin exceeds 9:1, that is, when the biodegradable polymer is contained in a manner exceeding the above weight ratio, the content of moxidectin in the microparticles is small, and in order to administer the drug at the required concentration, there is a problem of needing to administer a large number of microparticles.

[0057] More specifically, the biodegradable polymer in the first mixture comprises 15 to 60% by weight, preferably 15% by weight, but is not limited to this example.

[0058] The second step S200 is a step of preparing a second mixture, wherein a surfactant is dissolved in water to prepare a second mixture. If the biodegradable polymer solution can help form a stable emulsion, the use of the surfactant may be unrestricted. Specifically, it is selected from any one or more of the group consisting of nonionic surfactants, anionic surfactants, cationic surfactants and mixtures thereof, more specifically, it is selected from any one or more of the group consisting of methylcellulose, polyvinyl pyrrolidone, lecithin, gelatin, polyvinyl alcohol, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene castor oil derivatives, sodium lauryl sulfate, sodium stearate, esteramines, linear diamines, fatty amines and mixtures thereof, preferably polyvinyl alcohol, but not limited to the examples.

[0059] The third step S300 and the fourth step S400 are steps of injecting the first mixture and the second mixture into the microchannel formed on the wafer and causing them to flow.

[0060] More specifically, aluminum is deposited on a silicon wafer using an electron beam evaporator, and a photoresist is patterned on the aluminum using photolithography. The photoresist is then used as a mask to etch the aluminum, and after removing the photoresist, the silicon is etched using deep ion reactive etching (DRIE) using the aluminum as a mask. After removing the aluminum, the two electrodes are bonded and sealed with glass on the wafer to prepare the microchannel.

[0061] In addition, the average diameter of the microchannel is 60 to 150 μm, preferably 80 to 120 μm, and more preferably 100 μm, but is not limited to this example.

[0062] In addition, the cross-sectional width w and the cross-sectional height d of the microchannel are closely related to the average diameter d' of the prepared microparticles. Figure 8 As shown, the ratio of the width w of the microchannel cross section to the average diameter d' of the particles is in the range of 0.7 to 1.3; the ratio of the height d of the microchannel cross section to the average diameter d' of the particles is in the range of 0.7 to 1.3.

[0063] That is, when the average diameter d' of the microparticles to be prepared is determined, microparticles of the desired size can only be prepared by setting the width w and height d of the microchannel cross section to a ratio of 0.7 to 1.3 of d'.

[0064] In the third step S300, the first mixture is injected into the microchannel in the linear direction and allowed to flow; in the fourth step S400, the second mixture is injected into the microchannel formed on both sides or one side to form an intersection with the microchannel in the linear direction and allowed to flow.

[0065] That is, the first mixture flows along the microchannel in the linear direction, and the second mixture flows along the microchannels on both sides or one side of the microchannel in the linear direction so as to form an intersection with the microchannel in the linear direction, and merges with the first mixture flow.

[0066] At this time, when the first mixture is injected into the microchannel in the linear direction, it is injected under a certain pressure condition so that it flows at a certain flow rate, and the pressure condition at this time is 1000 to 1500 mbar, preferably 1500 mbar, but not limited to the example. In addition, when the second mixture is injected into the microchannels on both sides or one side, it is injected under a certain pressure condition so that it flows at a certain flow rate, and the pressure condition at this time is 1500 to 2000 mbar, preferably 2000 mbar, but not limited to the example.

[0067] That is, in order to make the second mixture flow forming an intersection with the first mixture flow flow at a higher flow rate than the first mixture injected into the microchannel in a linear direction, the second mixture is made to flow under a higher pressure condition.

[0068] As described above, the flow rates of the first mixture and the second mixture are different, and the flow rate of the second mixture is greater than that of the first mixture, so that at the place where the first mixture flow and the second mixture flow merge, the second mixture with a relatively faster flow rate compresses the first mixture. At this time, the biodegradable polymer and moxidectin in the first mixture are generated into spherical particles through the repulsive force of the first mixture and the second mixture. More specifically, particles in the form of moxidectin uniformly distributed in the spherical biodegradable polymer are formed.

[0069] The fifth step S500 is a step of collecting particles, in which the particles are collected in a water tank filled with the second mixture to prevent aggregation of the initially generated particles.

[0070] The fifth step S500 utilizes the second mixture prepared in the second step S200, that is, a mixed solution of a surfactant and water. After the second mixture is prepared in the second step S200, a portion is injected into the microchannel and the other portion is moved to the water tank of the fifth step S500 to prevent aggregation between the collected particles.

[0071] The sixth step S600 is a step of stirring the collected particles in a water tank, stirring the particles at a certain temperature and stirring speed, and removing the organic solvent on the surface of the particles by evaporation. At this time, the steps are carried out in the following order and stirring conditions: a first stirring step at 15 to 20°C at a speed of 200 to 400 rpm for 1 to 2 hours; after the first stirring step, a second stirring step at 20 to 30°C at a speed of 300 to 500 rpm for 1 to 2 hours; and after the second stirring step, a third stirring step at 40 to 50°C at a speed of 400 to 600 rpm for 3 to 5 hours.

[0072] The stirring speed and temperature of the particles are characterized in that the stirring speed and temperature are gradually increased and stirred in the first, second, and third stirring periods, respectively, and the evaporation speed of the organic solvent present on the surface of the particles can be adjusted according to the stepwise increase in temperature. That is, the organic solvent present on the surface of the particles is gradually evaporated, so that particles with smooth surfaces can be prepared.

[0073] More specifically, in the sixth step S600, the first stirring is performed at 15 to 20° C. for 1 to 2 hours, preferably at 17° C. for 1 hour. Then, the second stirring is performed at 20 to 30° C. for 1 to 2 hours, preferably at 25° C. for 1 hour. Then, the third stirring is performed at 40 to 50° C. for 3 to 5 hours, preferably at 45° C. for 4 hours.

[0074] The temperature of the first mixture and the second mixture when flowing in the microchannel is also 15 to 20°C, preferably 17°C. That is, after flowing in the microchannel and forming intersections to generate microparticles, the collected microparticles are kept at a constant low temperature of 15 to 20°C until the first stirring. Only by maintaining a low temperature during the preparation of microparticles can spherical particles be prepared and maintained. That is, in the case of non-low temperature conditions, it is difficult to prepare particles with a certain spherical shape.

[0075] Finally, the seventh step S700 is a step of washing and drying the particles, wherein the particles are washed multiple times with sterile filtered pure water by stirring to completely remove the organic solvent on the surface of the particles, remove the surfactant remaining in the particles, and then freeze-dry.

[0076] The final microparticles are in the form of moxidectin drug uniformly distributed in spherical biodegradable polymer microparticles, the average particle diameter of the microparticles is 80 to 130 μm, and the biodegradable polymer and moxidectin are contained in a weight ratio of 4:1 to 9:1. The weight ratio of the biodegradable polymer and moxidectin contained in the microparticles is the same as the weight ratio in the first mixture. As the microparticles are prepared and the organic solvent is completely removed by evaporation, microparticles containing the biodegradable polymer and moxidectin in the same ratio as the weight ratio in the first mixture can be prepared.

[0077] [Preparation Example: Preparation of Microparticles Containing Moxidectin]

[0078] Example 1

[0079] Poly(lactic-co-glycolic acid) (PLGA) and moxidectin were dissolved in dichloromethane to prepare a first mixture, wherein the poly(lactic-co-glycolic acid) copolymer in the first mixture was contained at a ratio of 15 wt %, and the weight ratio of the poly(lactic-co-glycolic acid) copolymer to moxidectin was 9:1.

[0080] Polyvinyl alcohol as a surfactant was mixed with water to prepare a second mixture containing 0.25 wt % of polyvinyl alcohol.

[0081] The first mixture and the second mixture were injected into the microchannel formed on the silicon wafer and flowed. At this time, in order to make the first mixture and the second mixture flow at a certain flow rate, the first mixture was flowed under a pressure condition of 1000 mbar, and the second mixture was flowed under a pressure condition of 2000 mbar. The temperature condition was maintained at 17°C.

[0082] The particles generated at the intersection where the first mixed flow and the second mixed flow meet are collected in a water tank filled with the second mixed flow. The particles collected in the water tank are stirred for the first time at 300 rpm at 17° C. for 1 hour, the temperature is raised to 25° C., the particles are stirred for the second time at 400 rpm for 1 hour, and the temperature is then raised to 45° C., and the particles are stirred for the third time at 500 rpm for 4 hours.

[0083] The stirred microparticles were washed several times with sterile filtered pure water and freeze-dried to prepare microparticles.

[0084] Example 2

[0085] The preparation was carried out in the same manner as in Example 1 except that the weight ratio of poly(lactic-co-glycolic acid) and moxidectin was 4:1.

[0086] Example 3

[0087] The preparation was carried out in the same manner as in Example 1 except that the weight ratio of poly(lactic-co-glycolic acid) and moxidectin was 2:1.

[0088] Example 4

[0089] The preparation was carried out in the same manner as in Example 1 except that the weight ratio of poly(lactic-co-glycolic acid) and moxidectin was 12:1.

[0090] Example 5 to Example 10

[0091] The preparation was carried out in the same manner as in Example 1, but after the fine particles were collected in the water tank containing the second mixture, a stirring step was carried out under the stirring conditions shown in Table 1 below.

[0092] Table 1

[0093]

[0094]

[0095] [Experimental Example 1: Drug Release Experiment of Microparticles Containing Moxidectin]

[0096] 1. In-vitro drug release assay

[0097] About 100 mg of the microparticles of Examples 1 to 4 were placed in a glass test container with a net capacity of 120 mL, and filled with 100 mL of the release test solution. As an accelerated test condition for drug release, the drug release test was performed by placing the microparticles in a 45°C water bath and shaking them back and forth at an amplitude of 4 cm and a frequency of 120 times / minute. When taking the sample, shake the bottle and take 1 mL. After centrifugation at 13000 rpm for 3 minutes, take the supernatant and analyze it by high performance liquid chromatography.

[0098] Table 2

[0099] Number of days 1 2 3 4 7 10 14 16 21 25 Example 3 28.1 42.5 57.2 69.3 92.5 94.2 94.3 95.1 95.1 96.3 Example 2 12.7 22.3 34.2 43.8 66.8 88.2 94.5 94.3 94.5 95.0 Example 1 6.5 12.3 20.1 28.1 50.2 72.0 86.2 93.1 93.5 96.2 Example 4 2.2 7.3 12.1 18.6 35.7 56.3 72.5 78.6 88.3 93.9

[0100] (unit%)

[0101] according to Figure 2 As shown in Table 2, in Examples 1 and 2, the moxidectin drug was released at a certain level until the 25th day, showing the effect of preventing or treating heartworms. On the contrary, in Example 3, the amount of drug released was too much at the beginning, and the release almost ended after 7 days, which had the problem of difficulty in showing the effect of long-term drug release. In addition, in Example 4, the amount of drug released in the initial stage was very small, and there was a problem that the therapeutic effect of the moxidectin drug was very small.

[0102] 2. In-vivo PK

[0103] The microparticles of Examples 1 and 2 were subjected to experiments in the same manner as in the experiment 1 above, and in vivo PK data were analyzed to confirm a sustained drug release effect over 3 months.

[0104] The results are as follows Figure 3 As shown. Figure 3 As shown, in the case of Examples 1 and 2, it was confirmed that moxidectin can be released for up to 3 months (90 days). Based on this result, it was confirmed that the microparticles of the present invention showed a moxidectin release effect that lasted for 3 months.

[0105] [Experimental Example 2: Study on the properties of microparticles]

[0106] In order to study the properties of the fine particles depending on the stirring conditions, the properties of the fine particles prepared under the conditions of Example 1 and Examples 5 to 10 were studied by SEM images.

[0107] The results are shown in Table 3 below.

[0108] Table 3

[0109] Experiments based on stirring conditions Microparticle preparation results Example 5 △ Example 6 △ Example 7 △ Example 8 △ Example 9 △ Example 10 △ Example 1 ○

[0110] △ indicates that due to the influence of residual solvent, the aggregation of particles occurs and the properties of the particles are uneven, such as Figure 4 and Figure 5 In contrast, in Example 1, Figure 6 and Figure 7 As shown in the SEM photograph, it was confirmed that the microparticles were uniformly formed and no aggregation occurred.

[0111] The preferred embodiments of the present invention are described in detail above, but the scope of the present invention is not limited thereto. Various modifications and improvements made by those skilled in the art using the basic concepts of the present invention defined in the claims are within the scope of the exemplary invention.

[0112] Industrial Applicability

[0113] The present invention relates to microparticles containing moxidectin and a preparation method thereof, and more particularly to microparticles containing moxidectin and a biodegradable polymer capable of preventing heartworms and a preparation method thereof.

Claims

1. A method for preparing microparticles containing moxidectin, wherein: include: Step 1: dissolving a biodegradable polymer and moxidectin in an organic solvent to prepare a first mixture; Step 2: dissolving a surfactant in water to prepare a second mixture; Step 3: injecting the first mixture of the step 1 into a microchannel in a linear direction to make it flow; Step 4: injecting the second mixture of the step 2 into a microchannel formed on two side surfaces or one side surface so as to form an intersection with the microchannel in the step 3 where the first mixture flows in a linear direction, and making the microchannel flow, so that the first mixture flow in the linear direction intersects with the second mixture flow, thereby preparing microparticles in which the moxidectin drug is uniformly distributed in spherical biodegradable polymer particles; Step 5: collecting microparticles generated at the intersection of the step 4; Step 6: stirring the microparticles collected in the step 5, and removing the organic solvent present in the microparticles by evaporation; and step 7: washing and drying the particles obtained in step 6; The sixth step comprises: step 6-1, stirring for the first time at 15 to 20° C. at a speed of 200 to 400 rpm for 1 to 2 hours; In step 6-2, after the first stirring step, stirring for a second time at 20 to 30° C. at a speed of 300 to 500 rpm for 1 to 2 hours; and in step 6-3, after the second stirring step, stirring for a third time at 40 to 50° C. at a speed of 400 to 600 rpm for 3 to 5 hours, The stirring temperature and stirring speed in step 6-1, step 6-2 and step 6-3 are increased in stages. The average particle diameter of the microparticles is 80 to 130 μm, and the biodegradable polymer is poly(lactic acid-co-glycolic acid). Furthermore, the microparticles contain the biodegradable polymer and moxidectin in a weight ratio of 4:1 to 9:

1.

2. The method for preparing microparticles containing moxidectin according to claim 1, wherein: The first mixture in the first step contains 15 to 60 wt % of the biodegradable polymer.

3. The method for preparing microparticles containing moxidectin according to claim 1, wherein: The organic solvent in the first step is at least one selected from the group consisting of dichloromethane, chloroform, ethyl chloride, dichloroethane, trichloroethane and a mixture thereof.

4. The method for preparing microparticles containing moxidectin according to claim 1, wherein: The second mixture in the second step comprises 0.2 wt % to 0.3 wt % of a surfactant.

5. The method for preparing microparticles containing moxidectin according to claim 1, wherein: The surfactant in the second step is at least one selected from the group consisting of nonionic surfactants, anionic surfactants, cationic surfactants and mixtures thereof.

6. The method for preparing microparticles containing moxidectin according to claim 1, wherein: The third step is to inject the first mixture into the microchannel in the linear direction at a pressure of 1000 to 1500 mbar.

7. The method for preparing microparticles containing moxidectin according to claim 1, wherein: The fourth step is to inject the second mixture into the microchannel formed on both sides or one side so as to form an intersection with the linear microchannel in which the first mixture flows, and the second mixture is injected at a pressure of 1500 to 2000 mbar.

8. The method for preparing microparticles containing moxidectin according to claim 1, wherein: The fifth step is to collect the particles in the water tank containing the second mixture.

9. The method for preparing microparticles containing moxidectin according to claim 2, wherein: The microchannels in the third and fourth steps are formed on the surface of the wafer, and the average diameter of the microchannels is 60 to 150 μm.

Images