WO2019050259A1 - Microparticules comprenant de la moxidectine et leur procédé de préparation - Google Patents

Microparticules comprenant de la moxidectine et leur procédé de préparation Download PDF

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Publication number
WO2019050259A1
WO2019050259A1 PCT/KR2018/010324 KR2018010324W WO2019050259A1 WO 2019050259 A1 WO2019050259 A1 WO 2019050259A1 KR 2018010324 W KR2018010324 W KR 2018010324W WO 2019050259 A1 WO2019050259 A1 WO 2019050259A1
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Prior art keywords
microparticles
mixture
moxifectin
biodegradable polymer
moxidectin
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PCT/KR2018/010324
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English (en)
Korean (ko)
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김주희
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(주)인벤티지랩
김주희
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Priority claimed from KR1020180031979A external-priority patent/KR102101969B1/ko
Application filed by (주)인벤티지랩, 김주희 filed Critical (주)인벤티지랩
Priority to EP18854665.9A priority Critical patent/EP3733164A4/fr
Priority to JP2020533631A priority patent/JP7040818B2/ja
Priority to CN201880010501.4A priority patent/CN110381924A/zh
Priority to US16/771,196 priority patent/US11931461B2/en
Publication of WO2019050259A1 publication Critical patent/WO2019050259A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles

Definitions

  • the present invention relates to microcapsules containing moxidectin and a method for preparing the microcapsules, and more particularly, to microcapsules containing moxidectin and a biodegradable polymer capable of preventing heartworms, and a method for producing the same.
  • Heartworm Disease is a parasite called Dirofilaria immitis, which is transmitted by mosquitoes. It infects dogs, cats and weasels. As the name suggests, heartworms parasitize the heart of mammals.
  • less than one heartworm can parasitize from one to as many as 200. Infection causes the pulmonary artery to become thick and inflamed, and the heart needs to do more to send blood to the lungs from heartworms. It also causes inflammation in the lungs. When the number of infected heartworms is low, there may be no specific symptoms, but in general, animals infected with heartworms may exhibit early symptoms such as avoidance of movement, coughing, and weight loss. In severe infections, symptoms such as severe cough, dyspnea and heart failure may occur. An animal infected with heartworms can die from heart failure if these symptoms occur.
  • the heartworm can be killed with capsolate, or melarsomine can be used to treat the disease.
  • capsolate or melarsomine can be used to treat the disease.
  • all of the above therapeutic agents have serious side effects such as irritation at the injection site and damage to the liver and kidney.
  • Heartworm antitussives include diethylcarbamazine (DEC) or monthly fed ivermectin, milbemycin, moxidectin, and selamectin, which are daily diets. Preventive medicines are all effective in preventing them when administered correctly, but they can be exposed to the risk of infection just by omitting several doses of mistakenly administered daily or monthly.
  • DEC diethylcarbamazine
  • ivermectin milbemycin
  • moxidectin moxidectin
  • selamectin which are daily diets.
  • Preventive medicines are all effective in preventing them when administered correctly, but they can be exposed to the risk of infection just by omitting several doses of mistakenly administered daily or monthly.
  • Patent Document 1 KR10-2006-0005472 A1
  • the present invention relates to microcapsules comprising moxidectin and a process for their preparation.
  • the present invention is based on the finding that, unlike the prior art cardiomyopathic remedy, which had a short half-life and had to be administered daily or monthly, when administered with microparticles containing moxifloxacin, the effect of preventing heartworm infection can be maintained for 3 to 6 months It is another object of the present invention to provide sustained-release microparticles and a method for producing the same.
  • the present invention relates to sustained-release particles containing moxidetin, which can maintain a long-term drug administration effect for a period of 3 months to 6 months, and at the same time, It is another object of the present invention to reduce the foreign body sensation and pain at the time of administration of the drug by controlling the release of the drug to keep the effective drug concentration constant.
  • a microparticle comprising moxidectin and a biodegradable polymer, wherein the microparticle is uniformly dispersed in spherical biodegradable polymer microparticles Wherein the average particle diameter of the microparticles is 80 to 130 ⁇ .
  • the microparticles of the present invention may contain a biodegradable polymer and moxidectin in a weight ratio of 4: 1 to 9: 1.
  • the microparticles of the present invention are capable of sustained release of moxifloxacin for 3 to 6 months.
  • the biodegradable polymer of the present invention is at least one selected from the group consisting of polylactic acid, polylactide, polylactic-co-glycolic acid, polylactide-co-glycolide (PLGA), polyphosphazine, polyiminocarbonate, Polyhydroxybutyrate, polyamino acid, and combinations thereof, and is preferably selected from the group consisting of polylactide-polylactide-polylactide-polylactide-polylactide-polylactide-Co-glycolide (PLGA), but is not limited to the above examples.
  • the microparticles of the present invention are prepared using microchannels, and the width w of the channel cross section ranges from 0.7 to 1.3 with respect to the average diameter d 'of the microparticles.
  • the microparticles of the present invention are prepared using microchannels, and the height (d) of the channel cross section ranges from 0.7 to 1.3 with respect to the average diameter (d ') of the microparticles.
  • the present invention relates to a pharmaceutical composition for preventing and treating heartworms comprising microparticles according to the present invention.
  • the present invention provides a method for producing a biodegradable polymer, comprising: 1) dissolving a biodegradable polymer and moxidectin in an organic solvent to prepare a first mixture; 2) dissolving the surfactant in water to prepare a second mixture; 3) injecting and flowing the first mixture of the step 1) into the microchannel in the linear direction; 4) The second mixture of step 2) is injected and flowed into the microchannels formed on both sides or one side so as to form an intersection with the microchannels flowing in the linear direction in the step 3) Preparing a microparticle wherein a linear flow of the mixture and a flow of the second mixture cross each other and moxidetin is evenly distributed on the spherical biodegradable polymer particle; 5) collecting the microparticles generated at the intersection of step 4); 6) stirring the microparticles collected in the step 5) to evaporate and remove the organic solvent present in the microparticles; And 7) washing and drying the microparticle
  • the first mixture of step 1) of the present invention may contain 15 to 60% by weight of the biodegradable polymer.
  • the first mixture of step 1) of the present invention may contain a biodegradable polymer and moxidectin in a weight ratio of 4: 1 to 9: 1.
  • the biodegradable polymer of the present invention is at least one selected from the group consisting of polylactic acid, polylactide, polylactic-co-glycolic acid, polylactide-co-glycolide (PLGA), polyphosphazine, polyiminocarbonate , Polyphosphoester, polyanhydride, polyorthoester, polycaprolactone, polyhydroxyvalate, polyhydroxybutyrate, polyamino acid, and combinations thereof, preferably polylactide -Co-glycolide (PLGA), but is not limited to the above example.
  • PLGA polylactide -Co-glycolide
  • the organic solvent in step 1) of the present invention is at least one selected from the group consisting of dichloromethane, chloroform, chloroethane, dichloroethane, trichloroethane, and mixtures thereof.
  • the second mixture of step 2) of the present invention may contain 0.2 wt% to 0.3 wt% of a surfactant.
  • the surfactant in the step 2) of the present invention is at least one selected from the group consisting of a nonionic surfactant, an anionic surfactant, a cationic surfactant, and a mixture thereof.
  • the step 3) of the present invention may inject the first mixture into the microchannel in the linear direction at a pressure of 1000 to 1500 mbar.
  • the step 4) of the present invention injects the second mixture into the microchannels formed on both sides or one side so as to form an intersection with the microchannel in the straight direction through which the first mixture flows , And the second mixture may be injected at a pressure of 1500 to 2000 mbar.
  • the step 5) of the present invention may collect microparticles in a water bath containing a mixed solution containing 0.2 wt% to 0.3 wt% of a surfactant.
  • the step 6) of the present invention comprises the steps of: 6-1) primary stirring at a speed of 200 to 400 rpm for 1 to 2 hours at 15 to 20 ⁇ ; 6-2) After the primary stirring step, the secondary stirring is carried out at a speed of 300 to 500 rpm at 20 to 30 DEG C for 1 to 2 hours; And 6-3) third stirring at a rate of 400 to 600 rpm for 3 to 5 hours at 40 to 50 DEG C after the secondary stirring step.
  • the microchannels of steps 3) and 4) of the present invention are formed on the surface of the wafer, and the average diameter of the microchannels is 60 to 150 ⁇ , preferably 80 to 120 ⁇ And more preferably 100 ⁇ , but it is not limited to the above example.
  • the present invention relates to microcapsules containing moxidetin and a method for producing the microcapsules, and more particularly, to microcapsules containing sustained-release microparticles capable of sustaining prevention of heartworms for 3 to 6 months upon administration of microcapsules containing moxidectin And a method for producing the same.
  • the present invention can be manufactured by maintaining the average diameter of the particles at a constant micro size, thereby reducing the foreign body sensation and pain upon administration to an animal as an injection, and facilitating administration to an injection.
  • FIG. 1 is a flow chart of a method for producing microspheres comprising moxidectin of the present invention.
  • FIG. 2 is a graph showing the drug release period according to the weight ratio of the biodegradable polymer and moxidectin of the present invention.
  • FIG. 3 is a graph showing a drug release period according to the weight ratio of the biodegradable polymer and moxidectin of the present invention.
  • FIG. 5 is a SEM photograph of microparticles according to a manufacturing method according to an embodiment of the present invention.
  • FIG. 6 is a SEM photograph of microparticles according to a manufacturing method according to an embodiment of the present invention.
  • FIG. 7 is a SEM photograph of microparticles according to the manufacturing method according to an embodiment of the present invention.
  • FIG. 8 is a diagram showing the relationship between the average diameter of the microparticles and the microchannel cross section.
  • the present invention relates to microcapsules comprising moxidectin and a biodegradable polymer, wherein the microcapsules have a shape in which a moxidectin drug is uniformly distributed in a spherical biodegradable polymer, and the microparticles have an average particle diameter of 80 to 130 ⁇ m And to microparticles comprising moxidectin.
  • the moxidectin of the present invention is a compound represented by the following general formula (1), which means a substance used as an anti-cardiovirus drug for animals.
  • FIG. 1 is a flow chart of a method for producing microspheres comprising moxidectin of the present invention.
  • the production of microcrystalline particles containing goxydetin of the present invention comprises the steps of: 1) preparing a first mixture (SlOO); 2) preparing a second mixture (S200); 3) injecting the first mixture into the microchannel in the linear direction (S300); 4) injecting the second mixture into the microchannels on both sides or one side (S40O); 5) Collecting microparticles (S500); 6) stirring the collected microparticles (S600); And 7) washing and drying microparticles (S700).
  • Step S100 is a step of preparing a first mixture, which comprises dissolving a biodegradable polymer and moxidetin in an organic solvent to prepare a first mixture, wherein the biodegradable polymer is polylactic acid, polylactide, poly Polyglycolic acid, polylactide-co-glycolide (PLGA), polyphosphazene, polyiminocarbonate, polyphosphoester, polyanhydride, polyorthoester, polycaprolactone, polyhydroxypoly Polyhydroxybutyrate, polyamino acid, and combinations thereof, and is preferably polylactide-co-glycolide (PLGA), but is not limited to the above examples.
  • the biodegradable polymer is polylactic acid, polylactide, poly Polyglycolic acid, polylactide-co-glycolide (PLGA), polyphosphazene, polyiminocarbonate, polyphosphoester, polyanhydride, polyorthoester, polycaprolactone, polyhydroxy
  • the organic solvent is not mixed with water and is, for example, any one or more selected from the group consisting of chloroform, chloroethane, dichloroethane, trichloroethane, and mixtures thereof.
  • the organic solvent is preferably dichloromethane, And organic solvent capable of dissolving biodegradable polymer and moxidectin. Any organic solvent easily selectable by those skilled in the art can be used without being limited to the above examples.
  • the first step (S100) is to prepare a first mixture in which a biodegradable polymer and moxidectin are dissolved.
  • an organic solvent is used as a solvent. It dissolves completely using an organic solvent, taking advantage of the dissolution properties of moxidectin and biodegradable polymer.
  • the first mixture comprises the biodegradable polymer and moxidectin in a weight ratio of 4: 1 to 9: 1, preferably 4: 1, but is not limited to examples.
  • the weight ratio of the biodegradable polymer and the moxidectin is less than 4: 1, that is, when the weight ratio of the biodegradable polymer is less than the above weight ratio, the weight ratio of the biodegradable polymer is smaller than that of the dendritic polymer, It is difficult to produce microparticles in which the moxidetin is evenly distributed in the polymer particles.
  • the weight ratio of the biodegradable polymer and the moxidectin exceeds 9: 1, that is, when the biodegradable polymer is mixed with the weight ratio
  • the content of moxifloxacin in the microparticles may be low and a problem may arise in that a large amount of microparticles must be administered to administer a desired concentration of the drug.
  • the biodegradable polymer in the first mixture comprises 15 to 60 wt%, preferably 15 wt%, but is not limited to the above examples.
  • the 2) step (S200) is a step of preparing a second mixture, wherein the surfactant is dissolved in water to prepare a second mixture.
  • the surfactant can be used without limitation as long as the biodegradable polymer solution can help form stable emulsion.
  • a nonionic surfactant is at least one selected from the group consisting of a nonionic surfactant, an anionic surfactant, a cationic surfactant, and a mixture thereof, and more specifically, methylcellulose, polyvinylpyrrolidone, lecithin, gelatin, polyvinyl alcohol , Polyoxyethylene sorbitan fatty acid ester, polyoxyethylene castor oil derivative, sodium lauryl sulfate, sodium stearate, ester amine, linear diamine, pattyamine, and mixtures thereof.
  • Polyvinyl alcohol but are not limited to examples.
  • the third step S300 and the fourth step S400 are the steps of injecting and flowing the first mixture and the second mixture into the microchannels formed on the wafer.
  • aluminum is deposited on a silicon wafer using an e-beam evaporator, and a photoresist is patterned on aluminum using a photolithography technique. Thereafter, aluminum is etched using a photoresist as a mask, the photoresist is removed, and the silicon is etched by DRIE (deep ion reactive etching) using aluminum as a mask. After the aluminum is removed, the glass is anodically bonded onto the wafer, Thereby manufacturing the above microchannel.
  • DRIE deep ion reactive etching
  • the average diameter of the microchannels is 60 to 150 ⁇ ⁇ , preferably 80 to 120 ⁇ ⁇ , more preferably 100 ⁇ ⁇ , but is not limited to the example.
  • the cross-sectional width w and the cross-sectional height d of the microchannel are closely related to the average diameter d 'of the microparticles to be produced.
  • the width w of the cross-section of the microchannel is in the range of 0.7 to 1.3 with respect to the average diameter d 'of the microparticles
  • the height d of the cross section of the microchannel is the average diameter d ') In the range of 0.7 to 1.3.
  • the length of the width w and height d of the microchannel cross section should be set in the range of 0.7 to 1.3 of d' It is possible to manufacture microparticles of desired size.
  • step S300 the first mixture is injected into the microchannel in the linear direction, and the fourth mixture is introduced into the microchannel in the linear direction.
  • step S400 Or into one side of the microchannel.
  • the first mixture flows along the microchannel in the linear direction
  • the second mixture flows along the microchannel forming the intersection with the microchannel in the linear direction on both sides or one side with respect to the linear microchannel, The flow of the first mixture is met.
  • the first mixture when the first mixture is injected into the microchannel in the linear direction, it is injected under a constant pressure condition and flowed at a constant flow rate, the pressure condition being 1000 to 1500 mbar, preferably 1500 mbar, but not limited to the example.
  • the second mixture when the second mixture is injected into the microchannels on both sides or one side, it is injected under a constant pressure condition and flowed at a constant flow rate.
  • the pressure condition is 1500 to 2000 mbar, preferably 2000 mbar, Do not.
  • the second mixture flows under higher pressure conditions to flow the flow of the second mixture, which intersects the flow of the first mixture, at a faster flow rate than the first mixture injected into the microchannel in the linear direction.
  • the flow of the first mixture and the second mixture are relatively more
  • the second mixture having a fast flow rate compresses the first mixture and the biodegradable polymer and the moxidectin in the first mixture form spherical microparticles due to the repulsive force of the first mixture and the second mixture, Specifically, microspheres in which moxidetin is uniformly distributed in a spherical biodegradable polymer are formed.
  • the step 5) collects the microparticles in the water tank containing the second mixture to prevent aggregation of the initially formed microparticles.
  • the fifth step S500 uses a second mixture prepared in the step S200, that is, a mixed solution of a surfactant and water. After the second mixture is prepared in the step S200, Is injected into the microchannel, and the other part is moved to the water tank of step S500, and a bundle between the collected micro particles is used to prevent the phenomenon.
  • a second mixture prepared in the step S200 that is, a mixed solution of a surfactant and water.
  • the step 6) S600 is a step of stirring the microparticles collected in the water tank.
  • the microparticles are stirred at a constant temperature and stirring speed to evaporate the organic solvent present on the surface of the microparticles.
  • the stirring conditions include a primary stirring at a speed of 200 to 400 rpm at 15 to 20 ° C for 1 to 2 hours; After the primary stirring step, the secondary stirring is performed at a speed of 300 to 500 rpm for 1 to 2 hours at 20 to 30 ⁇ . And the third stirring step at a speed of 400 to 600 rpm for 3 to 5 hours at 40 to 50 DEG C after the secondary stirring step.
  • the stirring speed and temperature for stirring the microparticles are characterized by gradually increasing the stirring speed and the temperature, respectively, according to the 1st, 2nd and 3rd stirring periods. As the temperature is raised stepwise, The rate of evaporation of the organic solvent present can be controlled. That is, the organic solvent present on the surface of the microparticles can be gradually evaporated to produce microparticles having a smooth surface.
  • step (S600) is firstly stirred at 15 to 20 ° C for 1 to 2 hours, preferably at 17 ° C for 1 hour. Then, the mixture is stirred at 20 to 30 ° C for 1 to 2 hours, preferably at 25 ° C for 1 hour. Then, the mixture is stirred at 40 to 50 ° C for 3 to 5 hours, preferably at 45 ° C for 4 hours.
  • the temperature at which the first mixture and the second mixture flow through the microchannel is also 15 to 20 ⁇ ⁇ , preferably 17 ⁇ ⁇ . That is, after flowing microchannels and forming crossing points to generate microparticles, the collected microparticles are kept at a low temperature of 15 to 20 DEG C constantly until the primary agitation. It is possible to manufacture and maintain spherical particles only if the temperature of the microparticles is kept low during the manufacturing process. That is, when the temperature is not low, it is difficult to produce a uniform spherical particle.
  • step (S700) is a step of washing and drying the microparticles.
  • the microparticles in which the organic solvent on the surface is completely removed by stirring are washed several times with the filtered, purified water to remove the surfactant remaining in the microparticles And then freeze-dried.
  • microparticles finally formed are spherical biodegradable polymer microparticles having a uniformly distributed moxidectin drug, the average particle diameter of the microparticles is 80 to 130 ⁇ , the biodegradable polymer and moxidectin are used in a ratio of 4: 9: 1.
  • the weight ratio of biodegradable polymer and moxidectin contained in the microparticles is equal to the weight ratio in the first mixture, which is obtained by preparing the microparticles and removing all of the organic solvent by evaporation, Microparticles containing the biodegradable polymer and moxidectin can be produced at the same ratio as the ratio of the biodegradable polymer and the moxidectin.
  • the first mixture was prepared by dissolving polylactide-co-glycolide (PLGA) and moxidectin in dichloromethane.
  • PLGA polylactide-co-glycolide
  • moxidectin moxidectin in dichloromethane.
  • the polylactide-co-glycolide in the first mixture is contained in a proportion of 15% by weight, and the weight ratio of polylactide-co-glycolide and moxydectin is 9: 1.
  • Polyvinyl alcohol as a surfactant was mixed with water to prepare a second mixture containing 0.25 wt% of polyvinyl alcohol.
  • the first mixture and the second mixture were injected into a microchannel formed on a silicon wafer and allowed to flow. At this time, in order to flow the first mixture and the second mixture at a constant 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 ⁇ ⁇ .
  • the microparticles generated at the intersection of the flow of the first mixture and the flow of the second mixture are collected in a water tank containing the second mixture.
  • the microparticles collected in the water tank were first stirred at 17 ° C for 1 hour at a speed of 300 rpm, then the temperature was raised to 25 ° C, the secondary stirring was carried out at 400 rpm for 1 hour, and then the temperature was raised to 45 ° C And the mixture was stirred for 3 hours at a rate of 500 rpm for 4 hours.
  • microparticles that had been stirred were washed several times with filtered water, and lyophilized to prepare microparticles.
  • the weight ratio of polylactide-co-glycolide and moxidectin was prepared in the same manner as in Example 1 except that the weight ratio was 4: 1.
  • the weight ratio of polylactide-co-glycolide and moxydectin was prepared in the same manner as in Example 1 except that the weight ratio was 2: 1.
  • the weight ratio of polylactide-co-glycolide and moxidectin was prepared in the same manner as in Example 1 except that the weight ratio was 12: 1.
  • microparticles were collected in a water tank containing the second mixture, and then stirred under the conditions shown in Table 1 below.
  • the drug release experiment is carried out by placing the sample in a 45 ° C water bath, reciprocating 4 cm of amplitude and 120 times / minute of shaking. When collecting specimens, shake well and mix 1 mL. After centrifugation at 13,000 rpm for 3 minutes, the supernatant was collected and analyzed by high performance liquid chromatography.
  • Example 2 According to Fig. 2 and Table 2, in the case of Examples 1 and 2, moxidectin drug was released to a certain level up to 25 days, and prevention or treatment effect of cardiac wasps could be exhibited. On the other hand, in Example 3, The amount of drug release is too much, and after 7 days, the release is almost completed, which is a difficult problem to exhibit a drug release effect for a long time. In addition, in the case of Example 4, the amount of initial drug release is too small, and there is a problem in that the therapeutic effect of the moxifloxacin drug is insufficient.
  • microparticles prepared under the conditions of Example 1 and Examples 5 to 10 were examined through SEM photographs to examine the properties of the microparticles according to the stirring conditions.
  • Example 5 Experiment according to agitation condition Production results of microparticles Example 5 ⁇ Example 6 ⁇ Example 7 ⁇ Example 8 ⁇ Example 9 ⁇ Example 10 ⁇ Example 1 ⁇
  • ⁇ means that the microparticles are aggregated due to the influence of the residual solvent, and the microparticles are uneven in shape.
  • Example 1 As shown in the SEM photograph of FIG. 7, it was confirmed that the properties of the microparticles were uniformly formed and no aggregation occurred.
  • the present invention relates to microcapsules containing moxidectin and a method for preparing the microcapsules, and more particularly, to microcapsules containing moxidectin and a biodegradable polymer capable of preventing heartworms, and a method for producing the same.

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Abstract

La présente invention concerne des microparticules comprenant de la moxidectine et un polymère biodégradable, où les microparticules comprenant la moxidectine ont une forme permettant au médicament de moxidectine d'être uniformément distribué dans des particules polymères biodégradables sphériques, et où le diamètre moyen de particule desdites microparticules est de 80-130 µm. La présente invention concerne : des microparticules à libération prolongée capables de maintenir en continu un effet de prévention de la dirofilariose pendant 3 à 6 mois par administration de microparticules comprenant de la moxidectine ; et leur procédé de préparation.De plus, la présente invention est préparée de façon que les diamètres moyens des particules aient une taille micrométrique prédéfinie, et réduisent ainsi la sensation de corps étranger et la douleur lors de l'administration à un animal par injection, ce qui permet de faciliter l'administration par injection.
PCT/KR2018/010324 2017-09-06 2018-09-05 Microparticules comprenant de la moxidectine et leur procédé de préparation WO2019050259A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP18854665.9A EP3733164A4 (fr) 2017-09-06 2018-09-05 Microparticules comprenant de la moxidectine et leur procédé de préparation
JP2020533631A JP7040818B2 (ja) 2017-09-06 2018-09-05 モキシデクチンを含むマイクロ粒子およびその製造方法
CN201880010501.4A CN110381924A (zh) 2017-09-06 2018-09-05 包含莫西菌素的微粒及其制备方法
US16/771,196 US11931461B2 (en) 2017-09-06 2018-09-05 Microparticles containing moxidectin, and preparation method therefor

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KR10-2017-0113669 2017-09-06
KR20170113669 2017-09-06
KR10-2018-0031979 2018-03-20
KR1020180031979A KR102101969B1 (ko) 2017-09-06 2018-03-20 목시덱틴을 포함하는 마이크로 입자 및 이의 제조 방법

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102464821B1 (ko) * 2022-04-13 2022-11-09 (주)인벤티지랩 목시덱틴을 포함하는 마이크로 입자 및 이를 포함하는 서방형 주사제 조성물

Citations (6)

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EP0537559A1 (fr) * 1991-10-15 1993-04-21 Atrix Laboratories, Inc. Compositions polymériques utilisables comme implants à libération controlée
KR20010041987A (ko) * 1998-03-19 2001-05-25 폴락 돈나 엘. 생활성 물질의 방출 조절용 액체 중합체성 조성물
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KR101351644B1 (ko) * 2005-08-19 2014-01-14 메리얼 리미티드 지속성 주사가능 기생충구충제 제형

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EP0537559A1 (fr) * 1991-10-15 1993-04-21 Atrix Laboratories, Inc. Compositions polymériques utilisables comme implants à libération controlée
KR20010041987A (ko) * 1998-03-19 2001-05-25 폴락 돈나 엘. 생활성 물질의 방출 조절용 액체 중합체성 조성물
WO2002009764A1 (fr) * 2000-07-13 2002-02-07 Ashmont Holdings Limited Compositions combinees
WO2003072112A1 (fr) * 2002-02-28 2003-09-04 Norbrook Laboratories Limited Composition antiparasitaire injectable a action prolongee
KR20060005472A (ko) 2004-07-13 2006-01-18 (주)이엘티사이언스 개 심장사상충 예방 및 박멸을 위한 경구용 이버멕틴페이스트 복합조성물 및 그의 제조방법
KR101351644B1 (ko) * 2005-08-19 2014-01-14 메리얼 리미티드 지속성 주사가능 기생충구충제 제형

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KR102464821B1 (ko) * 2022-04-13 2022-11-09 (주)인벤티지랩 목시덱틴을 포함하는 마이크로 입자 및 이를 포함하는 서방형 주사제 조성물

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