Long acting drug delivery system for treating breast cancer and preparation method and applications thereof

Abstract

The invention provides a long acting drug delivery system, which comprises fulvestrant or derivatives thereof and takes phospholipid as a sustained release material. The invention mainly discloses a high concentration formula of fulvestrant or derivatives thereof. The main component is fulvestrant or derivatives thereof. The sustained release material is different phospholipids or a mixture of phospholipids and different kinds of plant oil. The solvent is at least one of ethanol, ethyl lactate, 1,2-propylene glycol, and ethyl acetate. The analgesic is benzyl alcohol, lidocaine, procaine, or ropivacaine. The viscosity of the formula is 20-45 mPa.s, and the concentration of the formula is 60-300 mg / mL. The antioxidant of the formula is Ve, lipoic acid, and the like. The phospholipids can increase mutual solubility and has a sustained release function. The preparation is prepared in an aseptic filtration mode.

Description

technical field [0001] The invention belongs to the field of pharmaceutical sciences, and in particular relates to a long-acting drug delivery system of fulvestrant or its derivatives, its preparation method and application. Background technique [0002] Breast cancer is one of the most common malignant tumors in women. The latest survey report shows that breast cancer has become the disease that threatens women's health the most, and its incidence rate ranks first among female tumors in big cities. Fulvestrant injection is an intramuscular injection drug developed by AstraZeneca for the treatment of breast cancer. In April 2002, it was approved for marketing by the US FDA for the first time. It is mainly used to treat postmenopausal (including natural menopause and artificial menopause) estrogen receptor-positive locally advanced or metastatic breast cancer that has progressed during anti-estrogen therapy. [0003] Fulvestrant is a steroid anti-estrogen drug. Its chemical ...

AI Technical Summary

Problems solved by technology

The FASLODEX formula disclosed wherein can be seen: 1, have used the ethanol (10%) of high proportion to make solvent, and the local irritation that causes is big

2. Benzyl benzoate (15%) is used as a solubilizer: as everyone knows, benzyl benzoate is highly irritating to skin, eyes and mucous membranes; 3. High concentration of benzyl alcohol (10%) is used: However, it has a strong hemolytic effect, and it is easy to form induration that is difficult to absorb. If it is injected intramuscularly at a high concentration, these side effects will be very obvious; 4. The volume of a single injection is large; it is administered in a dose of 500g (EMA and FDA in 2015 have approval), requires intramuscular injection at two sites at once

In summary, FASLODEX has obvious and serious adverse reactions such as muscle irritation, induration, and injection pain, which bring great pain to patients after injection.

[0006] In addition, there are currently many studies devoted to the study of fulvestrant preparations, including microsphere preparations, improved fulvestrant oily preparations, emulsions, etc., all of which are looking for alternative solvents and dispersants, such as tetrahydrofuran polyethylene glycol Ether, polyethylene glycol, medium-chain triglycerides and poloxamers, etc., to solve the problems of low drug solubility, stability and irritation; The adverse reactions did not significantly improve

[0007] In 2012, the applicant declared a fulvestrant preparation with ethyl lactate as a carrier (patent number CN102600073B), an oily preparation of fulvestrant or its derivatives and its preparation method (patent number CN 102600065B), fulvestrant Sutran or its derivative sustained-release preparation and its preparation method (patent number CN 102600064 A), which protects related excipients with good solubility of fulvestrant, including ethyl lactate, ethyl acetate, propylene glycol, Methylformamide, dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran polyethylene glycol ether, etc. These excipients have significantly improved the solubility of fulvestrant, and may reduce the dose to a certain extent. However, the high content of castor oil is a major difficulty in improving irritation, and how to ensure a good sustained-release effect of the fulvestrant long-acting drug delivery system is another challenge. A major difficulty, this application has done a comparatively systematic research on this aspect

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