MICRONEEDLES AND METHODS FOR THEIR PRODUCTION Russian patent published in 2020 - IPC A61M37/00 A61M5/158 

FIELD: medicine; medical equipment.

SUBSTANCE: group of inventions relates to the field of application of microneedles for transportation of therapeutic, diagnostic, cosmetic, biological or other molecules inside the skin, beyond or through it or other fabric barriers. Matrix of microneedles for introduction of required substance into biological tissue contains main substrate having microneedle and opposite back side, a primary funnel-shaped portion extending from the micro-needle side of the base substrate, and two or more solid microneedles extending from the primary funnel-shaped portion. Two or more solid microneedles contain the required substance. Microneedle patch comprises a previously described microneedle matrix, an adhesive layer and an auxiliary layer attached to the base substrate. Auxiliary layer comprises tongue portion extending from one or more hard microneedle to allow user to retain tongue portion to manipulate patch without contact with two or more solid microneedles. Method of forming a microneedle array includes: (a) providing a casting mold having a top surface, an opposite bottom surface and a top surface opening, wherein the hole communicates with the first cavity proximal to the upper surface and with the second cavity located below the first cavity, wherein the first cavity defines the primary part of the funnel, wherein the second cavity defines at least one microneedle; (b) filling at least a second cavity through a hole in a casting mold with a first material which contains the desired substance dissolved or suspended in a first liquid medium; (c) drying the first material in the casting mold to remove at least a portion of the first liquid medium to form at least a portion of the sharpened end of the microneedle in the second cavity, wherein a portion of the pointed end comprises the desired substance; (d) filling the first cavity and the second cavity, provided that any of them is unoccupied during steps (b) and (c), through a hole in the casting mold with a second material which contains a matrix material dissolved or suspended in a second liquid medium; (e) drying the second material in a casting mold to remove at least a portion of the second liquid medium, to form (i) a primary portion of the funnel and (ii) any portion of the at least one microneedle not formed during steps (b) and (c), wherein primary part of funnel contains matrix material; (f) removing from the mold for pouring at least one microneedle together with a primary portion of the funnel attached thereto, wherein the desired substance in the at least one microneedle is greater than that found in the primary portion of the funnel, and wherein (i) the casting mold is gas-permeable and negative pressure is applied to the lower surface of the casting mold, (ii) the second cavity defines two or more microneedles extending from the primary funnel-shaped portion, and/or (iii) the casting mold is elastomer and step (f) comprises elastic deformation of the casting mold to facilitate separation of the casting mold from the primary funnel-shaped part and at least one microneedle. According to the second version, the method of creating a matrix of microneedle includes: (a) providing a non-porous and gas-permeable casting mold having a top surface, an opposite bottom surface, as well as holes on upper surface, wherein each hole is interconnected with cavity, which defines microneedle; (b) filling cavities through openings with a liquid material which contains the desired substance dissolved or suspended in a liquid medium; (c) drying liquid material in a casting mold for removing at least a portion of the liquid medium and forming microneedles which contain the desired substance; (d) removing the microneedle from the casting mold, wherein filling at step (b) is carried out with a pressure drop applied between the top and bottom surfaces of the casting mold. According to the third version, the method of creating a microneedle matrix includes: providing a casting mold consisting of two parts having an upper part and a lower part, wherein upper part has upper surface, opposite lower surface and hole passing through it, wherein opening defines upper cavity, wherein lower part has upper surface, opposite lower surface, as well as hole in upper surface, which is in fluid communication with upper cavity and which communicates with lower cavity, besides, lower cavity defines microneedle, wherein upper part and lower part are detachably connected together; filling at least the lower cavity through an opening in the upper part with a first material which contains the desired substance dissolved or suspended in the first liquid medium; drying the first material in the casting mold to remove at least a portion of the first liquid medium for forming the microneedle, which contains the desired substance; and removing the microneedle from the casting mold. According to the second embodiment of the microneedle matrix for introducing the required substance into the biological tissue, two or more solid microneedles contain the required substance and a matrix material. Required substance in two or more solid microneedles is located more than is located in the primary funnel-shaped part. Matrix of microneedles for introduction of two or more required substances into biological tissue contains: main substrate having microneedle and opposite back side, first funnel-shaped part extending from main substrate micro-needle side, a first matrix of two or more solid microneedles extending from the first funnel-shaped portion, a second funnel-shaped portion extending from the micro-needle side of the base substrate, and a second matrix of two or more solid microneedles extending from the second funnel-shaped portion. First and second funnel-shaped parts are elongated in the direction parallel to the main substrate. Microneedles of the first matrix contain the first required substance, and microneedles of the second matrix contain the second required substance which differs from the first required substance. In compliance with second version, patch with microneedle comprises one of said microneedle arrays described above. Method for administering a desired substance to a patient comprises providing one of the previously mentioned versions of a patch with microneedles, grip of tongue portion of plaster with microneedles, application of plaster with microneedles on tissue surface of patient and manual pressing on plaster with microneedles for application of pressure effective for introduction of microneedles into fabric. Method for administering a desired substance to a patient comprises presenting one of said microneedle matrices; using the microneedle matrix to the patient's tissue surface; introduction of microneedle matrix into tissue without use of applicator device.

EFFECT: inventions provide improved microneedle designs for better introduction into fabric, improved methods of producing microneedle, particularly for such improved structures.

64 cl, 27 dwg, 3 tbl