Biological degradable albumin derivant, pharmacy composition, preparation and application of the same

Abstract

The invention relates to a bio-degradable alb derivative and the related pharmaceutical combinations; wherein, the derivative introduces alkyl, or fatty acyl or deoxycholic acid in the alb skeleton to enable the amphiphilic property and form a nano-micelle by self-organization in water, and can enwrap the drugs through the double effects of the hydrophobic group, the alb molecular chain and the drugs, thereby substantially improving the drug enwrapping ability of the alb and prolonging the stability time. The excipient can be used as the carrier for organic drugs, water-insoluble drugs or dugs with poor water solubility and the carrier of amphipathic drugs, and for the administration inside the vein or muscle injection and oral administration. The preparation method of the bio-degradable alb derivative and the related pharmaceutical combinations is simple and of mature techniques, which is suitable for large scale continuous production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a biodegradable 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, solubilization by surfact...

AI Technical Summary

Problems solved by technology

However, the solubility of paclitaxel in water is extremely low (_ [US Bristol Myers Squibb (BMS) Company], Anzatax _ (Australian Faulding company) and domestic perilla _ Taxol _ etc. all use polyoxyethylene castor oil (Cremophor EL)-absolute ethanol (50:50, v / v) as paclitaxel composite solvent, 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

Albumin self-assembled nanomicelles have not been reported in any literature and patents

Images