METHODS OF IMPROVED DELIVERY OF ACTIVE AGENTS IN TUMOUR Russian patent published in 2020 - IPC A61M37/00 

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, namely to delivery of agents through skin, and can be used for delivery of one or more agents in one or more susceptible tumours in an individual and treating a subject with a disease involving one or more tumours, by administering one or more biologically active agents into one or more tumours. Method for delivering one or more agents into one or more susceptible tumours in an individual involves: (a) use of one or more needles having a plurality of needles in relation to one or more skin regions comprising a vascular network or a lymphatic vasculature, and (b) administering the total amount of the liquid dosage form in multiple portions of the dose of one or more agents at a controlled flow rate upon administration. One or more needle arrays provide contact of one or more layers of the epidermis with one or more reversible permeability enhancers. Reverse permeability enhancers can be chemical, physical or electrical. Reversible increase in the permeability of one or more cells of the barrier layer of the epidermis is induced for at least one or more agents. Controlled flow rate at introduction makes from 0.01 to 100 mcl/h on each of needles. Total combined flow rate controlled by the introduction is from 0.02 to 50,000 mcl/h/cm² based on the total surface area of one or more arrays of needles which are in contact with the subject's skin. Each portion of the dose of one or more agents is independently administered at multiple independent depth values within range of 1 to 500 mcm, outside the epidermis most surface layer of the subject, but still within a subject's epidermis, which is characterized by a Gaussian distribution of depth values in the epidermis, before any further diffusion or movement of one or more agents in the epidermis. After the stage of introduction, one or more agents are moved or diffused deeper through the epidermis, through a basal layer of the epidermis and into the underlying part of the viable derma with the capture of part of one or more biologically active agents by one or more receptive interlaces of the blood capillaries or lymphatic capillary braids. After the introduction, the permeability of one or more cells of the barrier layer returns to the state before bringing the epidermis into contact with one or more permeability enhancers. Method of treating a subject with a disease involving one or more tumours by administering one or more biologically active agents into one or more tumours involves: (a) use of one or more needles having a plurality of needles in relation to one or more skin regions comprising a vascular network and a lymphatic vasculature, and (b) administering the total amount of the liquid dosage form in multiple dose portions of the one or more biologically active agents at a controlled flow rate when administered by the needle array. Needle array provides contact of one or more layers of the epidermis with one or more reversible permeability enhancers which induce a reversible increase in the permeability of one or more cells of the barrier layer of the epidermis for at least one or more biologically active agents. Each portion of the dose of one or more biologically active agents is independently administered at multiple independent depth values in the epidermis before any further diffusion or movement of one or more biologically active agents in the epidermis. After the stage of introduction, one or more biologically active agents are moved or diffused deeper through the epidermis, through a basal layer of the epidermis and into the underlying part of the viable derma with the capture of part of one or more biologically active agents by one or more receptive interlaces of the blood capillaries or lymphatic capillary braids. After introduction and capture, one or more biologically active agents are circulated through the vasculature or lymphatic vasculature to one or more tumours. One or more biologically active agents are delivered in one or more tumours in a higher concentration as compared to intravenous, intradermal or subcutaneous delivery of identical one or more biologically active agents.

EFFECT: group of inventions provides the capture of one or more agents with lymphatic tissues, particularly one or more receptive lymphatic capillary plexuses in viable skin by administering a needle array in multiple portions of the dose at a controlled flow rate when administered with an increase in reversible permeability.

43 cl, 14 dwg