Self-emulsifying doxorubicin nanometer medicament and preparation method thereof

Abstract

The invention discloses a self-emulsifying doxorubicin nanometer medicament, which is prepared by connecting carbonyl of 8-hydroxyl acetyl on doxorubicin and hydrophilic groups by in-vivo degradable chemical bonds; and a precursor of the medicament introduces small molecular hydrophilic groups or hydrophilic polymer short chains into hydrophobic doxorubicin (DOX) molecules, so that the DOX molecules are hydrophilic-hydrophobic molecules. The self-emulsifying doxorubicin nanometer medicament can be subjected to self-assembly in water to form nanometer granules or nanometer vesicles, can target tumor tissues by utilizing the enhanced permeability and retention (EPR) effect, and has the characteristics of maintaining the high cytotoxicity of the doxorubicin, along with high medicament carrying capacity, and small toxic and side effects. The invention also discloses a preparation method for the self-emulsifying doxorubicin nanometer medicament which has high medicament carrying capacity and high yield and is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of preparation methods of medicines, in particular to a self-emulsifying doxorubicin nanomedicine and a preparation method thereof. Background technique [0002] Doxorubicin (DOX), the English name is Doxorubicin or Adriamycin, alias hydroxyzhengdomycin, doxorubicin or daunorubicin, commercially available is generally doxorubicin hydrochloride, its molecular formula is C 27 H 29 NO 11 ·HCl, molecular weight is 580.02, CAS number: 25316-40-9, the structural formula is as follows: [0003] [0004] Doxorubicin is a broad-spectrum antitumor drug, which is a cycle non-specific drug, and has a killing effect on tumor cells in various growth cycles. It has strong cytotoxicity, and its mechanism of action is mainly to embed DNA to inhibit the synthesis of nucleic acid, so as to achieve the purpose of controlling the spread of tumor cells and killing tumor cells. However, due to its extremely poor water solubility and ...

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Problems solved by technology

However, the carriers used in these bonds are all high molecular weight polymers, so that the entire bond is soluble in water, resulting in a very low drug loading (mostly 1%-2% of the weight of the preparation)

At the same time, high molecular weight polymers can make the bond have an EPR effect, which requires a large amount of polymer auxiliary materials to deliver the required drug dose, but high molecular weight polymers are generally difficult to exclude from the body, and their accumulation in the body will cause toxic side effects

In addition, the Chinese patent application with the application number 200910023552.3 has introduced the bonding of DOX to the high molecular weight polyethylene glycol (molecular weight is 6000) segment, but it introduces high molecular weight polyethylene glycol in order to make the target product soluble in water. Ethylene glycol, resulting in very low drug loading, and at the same time, the target product obtained cannot effectively form nano-drugs, resulting in the inability to effectively use the EPR effect to target DOX to cancer tissues

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