Fatty acid sustained-release composition for injection and preparation method and application thereof

Abstract

The invention discloses a fatty acid sustained-release composition for injection and a preparation method and application thereof, and belongs to the technical field of medicines. The fatty acid sustained-release composition for injection is prepared from an active medicine, fatty acid and a solvent. According to the fatty acid sustained-release composition for injection and the preparation method and application thereof, the fatty acid is used as an in-situ gel matrix, after the in-situ gel matrix is injected subcutaneously or muscles, the fatty acid can rapidly entrap a medicine to form a solid implant, the medicine and the fatty acid can form a porous net-shaped cross-linked structure instead of simple physical mixing, and the medicine and the fatty acid form a conjugate and then are slowly dissolved out in an aqueous environment, the fatty acid can also be absorbed by the fat-soluble medicine, so that the fat-soluble medicine is released more completely; and by adjusting the prescription proportion, the clinical administration requirement of the medicine with the medicine release period of 3 days-15 days can be met.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a slow-release composition for injection using fatty acid as an in-situ gel matrix, a preparation method and application thereof. Background technique [0002] For diseases that require long-term injection therapy (such as schizophrenia), multiple administrations or continuous injections are required to ensure the efficacy of the drug, which not only increases the physical, psychological and economic burden of the patient, but also increases the burden due to the number of administrations. If there are too many, the fluctuation of steady-state blood drug concentration will increase, and it will be more likely to have adverse effects on drugs with a narrow therapeutic window (such as aminophylline, etc.), or long-term high-frequency injections will cause discomfort to patients, such as pain, local Symptoms such as redness, swelling, allergies, etc., lead to other symp...

AI Technical Summary

Problems solved by technology

[0004] However, the application of the existing PLGA system also has the following limitations: (1) slow release rate: in the field of sustained and controlled release of drugs, different drug carrier materials are required to have different drug release rates, and due to the strong hydrophobicity of the PLGA surface, the formation of The solid gel structure of the solid gel is dense, and the drug (especially the hydrophobic drug) is encapsulated in it and released slowly through diffusion, dissolution or polymer erosion.

The drug release cycle of marketed products is generally several months (US patents 6,565,874, 6,528,080, 6,461,631, 6,395,293, 4,938,763, 5,077,049, and 20130210853), such as (release time is 1, 3, 4, 6 months), (release time is 1 month), (The release time is 1 month), etc.; (2) Long degradation time: the degradation time of different types of PLGA is 1 to 6 months, and only relying on the molecular weight and molecular weight distribution of PLGA homopolymer to adjust the degradation rate has great limitations. A single homopolymer in situ gel cannot satisfy the release of drugs with a release period of less than one month; (3) Drug loading limitation: due to high safety and high water compatibility, the solvents of PLGA systems currently on the market are all N -Methyl-2-pyrrolidone (NMP), but the solubility of the drug in the solvent and the limitation of the in situ gel injection volume (generally less than 2mL), the PLGA system is mainly used for small doses of drugs or drugs with high solubility in NMP, E.g (monthly administration of 7.5mg), (monthly administration of 90mg or 120mg), (The solubility of buprenorphine in NMP is greater than 300mg / mL)

And for the medicine of this dosage of medicine (monthly administration 300mg~600mg), low solubility in amphipathic solvent, the existing PLGA system cannot adapt to the clinical administration of medicine because the medicine release cycle is too long; meanwhile, The preparation system also has the relatively serious shortcoming of sudden release, which seriously affects the release stability of its long-acting preparation and is not conducive to product quality control.

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