Method of fixing and expressing physiologically active substance

Abstract

The present invention provides methods for retaining and expressing physiologically active substances in a target tissue-specific-manner, by administering the physiologically active substances to target submucous tissue. Specifically, the present inventors demonstrated that, when physiologically active substances were directly administered into submucous tissues without using a carrier, the physiologically active substances were effectively and safely retained at the administration sites over long periods without loss and diffusion, and produced the effect acting in a reservoir-like fashion. The physiologically active substances administered as described above were demonstrated to produce the therapeutic effect without having an influence on organs other than the administered organ.

Description

TECHNICAL FIELD[0001]The present invention relates to methods for retaining and expressing physiologically active substances in a target tissue-specific manner, in which the physiologically active substances are administered to the target submucous tissue.BACKGROUND ART[0002]At the nonclinical experiment level, it is now becoming possible to treat disease-model animals using techniques of introducing genes of interest, or conversely, suppressing the expression of genes of interest through RNA interference. In the case of “nucleic acid pharmaceutical agents” using such a gene or an siRNA (generally termed “nucleic acid”), the nucleic acid administered to the living body needs to continuously produce its effect and be retained over a long period. A critical factor in achieving the therapeutic effect of nucleic acid pharmaceutical agents is how the drug delivery system (DDS) is designed.[0003]Meanwhile, when nucleic acids are administered to the body as is, they are rapidly degraded an...

AI Technical Summary

Benefits of technology

[0029]The present invention provides a Drug Delivery System (DDS) for maintaining a physiologically active substance (for example, a nucleic acid, protein, carbohydrate, lipid, low-molecular-weight compound, etc.) in a target submucous tissue over a long period, for continuously producing a physiologically active substance useful to the living body, or for continuously removing a physiologically active substance that is harmful to the living body. The present invention enables safe and effective retention of physiologically active substances at the administration sites over long periods without assistance of a carrier. Thus, physiologically active substances can be retained without considering side effects of carriers as before. This significantly increases the clinical feasibility of pharmaceutical agents using physiologically active substances (for example, nucleic acid pharmaceutical agents). In addition, the above-described pharmaceutical agents have very little systemic side effects, because they specifically produce their effects at the injection sites. Thus, the pharmaceutical agents are much safer than conventional methods.

[0030]Endoscopic examination (of the esophagus, stomach, and small and large intestines) is routinely carried when diagnosing gastrointestinal diseases. Thus, the present invention has the advantage in that physiologically active substances (for example, nucleic acids) can be injected (for treatment) at the same time as diagnosis. The present invention is also expected to be applicable to the submucous tissues of the nose, subconjunctival tissue, or such, and thus enables actual clinical use of pharmaceuticals for cranial nerve diseases or ophthalmic diseases, in which physiologically active substances have been difficult to deliver in the past. Thus the methods of the present invention have a superior effect than the conventional local administration methods, specifically, enemas, nasal drips, and ocular instillations.

Problems solved by technology

Meanwhile, when nucleic acids are administered to the body as is, they are rapidly degraded and thus fail to work.

However, nucleic acid pharmaceutical agents have a serious disadvantage in that the carrier itself may induce an adverse immune response or such in the body and thus not only the nucleic acid but also carrier must be assessed for its influence on the body.

Another problem is that, even when a carrier is used, normally, the introduced nucleic acid can only be retained for about one week.

Thus, the above-described problems still remain unsolved.[Patent Document 1] Japanese Patent Application Kohyo Publication No.

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