Preparation and application of amphiphilic albumin derivative and pharmaceutical composition thereof

Abstract

The invention relates to a biodegradable amphiphilic albumin derivative and a pharmaceutical composition thereof. In the biodegradable amphiphilic albumin derivative, hydrophilic long-chain polyethyleneglycol and alkyl (acyl) group or (deoxidized) cholic acid are led to an albumin skeleton so that the amphiphilic albumin derivative is amphipathic and is self-assembled in water to form nano-micelle. The biodegradable amphiphilic albumin derivative is characterized in that medicament can be encapsulated through the double actions of a hydrophobic group and an albumin molecule chain with the medicament, and the capacity of the albumin encapsulating the medicament is markedly improved; in addition, a hydrophilic long-chain can reduce the immunogenicity of the albumin and improve the nano-micelle surface hydrophilicity so that the stability of the nano-micelle in aqueous medium can be improved and the nano-micelle has long-circulation characteristics in a body. The pharmaceutical composition of the biodegradable amphiphilic albumin derivative can be used as the carrier of organic medicament, water-insoluble or insoluble medicament and amphiphilic medicament, can be used for intravascular administration, intramuscular injection administration, oral administration, cavitary administration or external administration. The invention can be prepared with simple method and mature process and is suitable of large-scale continuous production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a biodegradable amphiphilic albumin derivative as a drug carrier, and also relates to a preparation method and application of the carrier. Background technique [0002] The biggest obstacle to the administration of poorly soluble drugs (especially injection administration) is low solubility, which makes it difficult to prepare suitable preparations. It is often necessary to adopt various methods to increase solubility, such as preparing the drug into a salt, adding a latent solvent, adding a co-solvent, and adding a surfactant to solubilize. Since salt formation often requires strong acid or strong alkali conditions, it is often not applicable to many drugs, and there are few physiologically safe latent solvents, and the dosage is limited; the safety of co-solvents that increase drug solubility by forming complexes with drugs is not easy Assured, therefore, solubilizatio...

AI Technical Summary

Problems solved by technology

However, the solubility of paclitaxel in water is extremely low ( [US Bristol Myers Squibb (BMS) Company], (Australian Faulding company) and domestic etc. all use polyoxyethylene castor oil (Cremophor EL)-absolute ethanol (50:50, v / v) as the compound solvent of paclitaxel, and there are following defects in this solubilization method: ①Critical micellar concentration (Critical micellar concentration) of Cremophor EL , CMC) is relatively high, micelles are easy to dissociate during clinical dilution, leading to drug precipitation, so the infusion tube must have an online filter device; ② Cremophor EL in the prescription will cause the release of histamine in the body, and some patients will suffer from the release of histamine within a few minutes after administration. Drug-induced rash, shortness of breath, bronchospasm, hypotension and other allergic reactions may occur. Even if hydrocortisone is used at the same time, the incidence of allergic reactions still reaches 10% to 30%. In addition, Cremophor EL can also cause nephrotoxicity and neurotoxicity , cardiotoxicity and other side effects; ③Cremophor EL in the injection can leach out a large amount of plasticizer diethyl ethyl phthalate (DEHP) when in contact with polyvinyl chloride plastic tubes and infusion bags, causing toxicity

This type of albumin self-assembled nanomicelle has not been reported in any literature and patents

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