Method for improving target effect of receptor targeting preparation based on folic acid compounds

Abstract

The invention relates to the field of medicinal preparations and particularly relates to a method for improving an active targeting effect of an active targeting preparation based on folic acid compounds by increasing distribution of targeting groups, namely folic acid compound groups, of the active targeting preparation in external water phase. The method is characterized in that the key difference between the method and the conventional preparation method is that normal water, osmotic-pressure regulator solution or neutral buffer saline solution does not serve as the water phase, but alkalescence solution with pH being 7.5-10.0 serves as the water phase. The active targeting effect of the receptor targeting preparation prepared by the method can be improved.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a method for increasing the distribution of targeting groups in active targeting preparations based on folic acid compounds, that is, folic acid compound groups, in the external water phase, thereby improving the active targeting effect of the preparations. Background technique [0002] Folic acid (FA) can be reduced to tetrahydrofolate, which is a coenzyme of one-carbon unit transferase, involved in one-carbon unit metabolism and de novo synthesis of purine and thymine. The expression of folate receptors in normal tissues is highly conserved, only in lung, kidney, choroid and placenta, there is low to moderate expression, and the β subtype is the main one, but in most malignant tumors, such as ovarian cancer, uterus Highly expressed in endometrial cancer, prostate cancer, kidney cancer, breast cancer, lung cancer, colon cancer and nasopharyngeal cancer, sometimes 100-3...

AI Technical Summary

Problems solved by technology

This patent better solves the problem that most of the folic acid groups in the classic modification method of folic acid receptor targeting preparations are coated on the hydrophobic inner core of the preparation and cannot be exposed, thereby affecting the interaction with target cell surface receptors. The preparation process is cumbersome and the phosphatidylethanolamine group of phosphatidylethanolamine-polyethylene glycol 2000-folate, that is, the phospholipid group, has limited insertion efficiency into liposomes during incubation

At the same time, the versatility of the incubation method is very limited. The incubation method requires that the surface of the main body of the preparation to be modified is hydrophilic and semi-solid, and the targeting material must contain a group with the same structure as the surface material of the preparation or a group with high affinity to facilitate its insertion and fusion. , taking this patent as an example, if the other end of the polyethylene glycol chain or other hydrophilic chain used to connect the folic acid group is not connected to phospholipids but other amphiphilic materials or hydrophobic materials, then there is a combination of the material and the lipid The affinity of the body phospholipid layer is not strong or can not be inserted. If the surface of the preparation is hydrophobic, the preparation system only maintains physical stability through charge repulsion or other forces between the preparations, or the main surface of the preparation is solid, which does not have the appropriate If there is no fluidity, the incubation method cannot be used for the modification of active targeting agents at all, because the key process of post-insertion cannot be realized at all

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