Injectable drug delivery depot of fulvestrant or derivative thereof, preparation method and application thereof

Abstract

The invention provides an injectable drug delivery depot of fulvestrant or a derivative thereof. The injectable drug delivery depot comprises fulvestrant or the derivative thereof, a solvent, a depotmaterial and an analgesic. According to the injectable drug delivery depot of fulvestrant prepared by the invention, the defects of high irritation and insufficient safety of commercially available products can be overcome; an sufficiently high active component concentration is realized, so an injection volume is greatly reduced, the compliance of patients is greatly improved, a better sustained-release effect in treatment can be obtained, and administration frequency is reduced; and a sustained-release effect can last for 30 days or more after single dose of the injectable drug delivery depotto a human body.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an injectable drug delivery reservoir of fulvestrant or its derivatives, a preparation method and application thereof. Background technique [0002] Breast cancer is the number one malignant tumor in women, accounting for about 17% of all malignant tumors in women, and generally occurs in the age of 40 to 60. In the past ten years, the incidence of breast cancer in my country has shown an obvious increasing trend year by year, and the age of onset About ten years earlier than the global average age. [0003] The current medical research results have confirmed that the expression of estrogen receptors in cancer cells in breast cancer patients is higher than normal. The growth rate of such cancer cells is positively correlated with the level of estrogen in the body. Therefore, drugs that inhibit estrogen in the body Receptor levels are an important approach in the trea...

AI Technical Summary

Problems solved by technology

[0007] Although this product improves drug solubility to a certain extent, adverse reactions such as injection pain, muscle irritation, and induration caused by high-concentration use of alcohol solvents such as ethanol, benzyl alcohol, and benzyl alcohol benzyl ester bring greater pain to patients. Painful, the results of the rabbit irritation test show that local muscle tissue can return to normal within 45 days after local intramuscular injection of 1 mL

[0008] The drug concentration of 50mg / mL in this product is still relatively low, and it is difficult to meet the requirements of clinical use. At present, when this fulvestrant injection is used clinically, in order to achieve a longer drug action time and obtain better clinical effects, it is necessary to Increase the injection volume to intramuscular injection of 500mg / month, but at the current drug concentration, a total of 10mL has to be injected once or twice, resulting in a larger amount of non-aqueous solvent usage, which will cause great pain to the patient

[0009] At present, there are many studies on fulvestrant preparations, most of which are looking for alternative solvents and dispersants that can improve the solubility of fulvestrant, so as to improve the problem of low drug solubility

For example, in the existing technology, the solubility of fulvestrant is improved by co-solvents such as lactic acid esters, and the drug content can reach 100 mg / mL, but the drug release time is the same as that of the original research; the existing technology uses ether compounds to increase the drug content to 10~ 200mg / mL; the prior art improves the drug content to 10-150mg / mL by azone, but still needs to add enough alcohol etc.; the prior art prepares fulvestrant liposome injection by phospholipid, cholesterol, etc. The drug loading can reach 100 mg / mL, but it requires a large amount of surfactants, the irritation and hemolysis are difficult to guarantee, and the appearance, sterilization, irritation and safety of liposome injections have always been difficult. The problem to be solved; the prior art also uses PLGA as a carrier to prepare sustained-release microspheres and phospholipids as sustained-release materials to prepare long-acting drug delivery systems, and has achieved some beneficial effects, but there are still problems such as insufficient drug loading and stable preparations. Weaknesses such as poor sex

Existing technologies cannot solve the problems of drug irritation and patient compliance well, and cannot provide a better solution for clinical use

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