Microneedle patch for transdermal injections
The disclosure belongs to medical devices and particularly to soluble microneedle patches and small dose medical injection devices for transdermal injections of medical and cosmetic materials to patients. It also belongs to micro-electro-mechanical systems technology (MEMS). The materials can include vitamins, proteins, glycerides, vaccines, mono-, oligo- or polysaccharides, organic acids and its salts, as well as combinations of the said materials and their derivatives. The disclosed micro-needle patch can be used for medical purposes in hospitals, outpatient and home conditions.
1. A microneedle patch, comprising:
a substrate;
a microneedle matrix containing more than one microneedle, wherein each microneedle has a base, a cone-shaped sharp end made of a mixture of a carrier bio-soluble material and an active component, and a multi-branch structure in between the sharp end and the base, the multi-branch structure being wider than the sharp end and comprises a plurality of cone-shaped branches that are geometrically intersected with each other and made of a bio-soluble material;
a base film connecting the bases of the microneedles in the microneedle matrix with an inner surface and attached to the substrate with an outer surface;
wherein the sharp end of the microneedle is located on top of the multi-branch structure of the microneedle, and
wherein the substrate and the base film are made of flexible materials.
2. The microneedle patch of claim 1 , wherein the sharp end of the microneedle is harder than the rest of the microneedle.
3. The microneedle patch of claim 2 , wherein the base film is made of a non soluble material.
4. The microneedle patch of claim 1 , wherein the base film is made of a soluble material.
5. The microneedle patch of claim 1 , wherein the base film overlaps with base parts of the multi-branch structure of the microneedles.
6. The microneedle patch of claim 1 , wherein the substrate is configured to be disconnectable from the microneedle matrix and the base film after an injection of the patch to a skin, wherein the microneedle matrix and the base film remain on the skin after said injection.
7. The microneedle patch of claim 1 , wherein the microneedle matrix, the base film and the substrate are fabricated in the same fabrication process.
8. The microneedle patch of claim 1 , wherein the substrate is fabricated separately from the microneedle matrix.
9. The microneedle patch of claim 8 , where the substrate is integrated with the microneedle matrix and the base film through an adhesive layer.
10. The microneedle patch of claim 9 , wherein the outer surface of the base film is provided with the adhesive layer for integration with the substrate.
11. The microneedle patch of claim 1 , wherein a height of the microneedles ranges between 300 to 700 micrometers.
12. The microneedle patch of claim 1 , wherein a ratio of specific dissolution rates of the mixture of the carrier bio-soluble agent with the active component and the bio-soluble material is in the range from 1: 200,000 to 1:950,000.
13. The microneedle patch of claim 1 , wherein the base film has a thickness between 20 to 200 micrometers and the inner surface of the said base film is configured to be put into contact with a skin.
14. The microneedle patch of claim 1 , wherein the active component is a medical drug that is chosen from the following groups: non-steroidal anti-inflammatory drugs, or anti-allergic agents, or antiseptic and disinfectants, or antimicrobial agents, or vaccines and serums, or vitamins and analogs, or diagnostic agents, or homeopathic remedies, or hormonal preparations or agents for correction of metabolic processes, or agents used in dermatology and venereology, or preparations based on plant raw materials, or enzymes and anti-ferment preparations, or derivatives of these groups of substances in various combinations.
15. The microneedle patch of claim 1 , wherein the carrier bio-soluble agent comprises components selected from the group consisting of polymers of lactic acid, polymers of glycolic acid, copolymers of lactide and glycolide, polycaprolactone, polyanhydrides poly-p-dioquavane, polyurethanes, 1,4-diisocyanate butane, polybutyric acid, polyvaleric acid; copolymers of lactide and caprolactone; copolymers of cyclic olefins, polyvinyl alcohol, polyvinylpyrrolidone, chitosan, starch, cellulose acetate, hyaluronic acid, chondroitinsulfate, collagen, copolymers of collagen and polyvinyl alcohol, gelatin, gluten, and any mixtures thereof.
16. The microneedle patch of claim 1 , wherein the bio-soluble material comprises carboxymethylcellulose, or sodium carboxymethylcellulose, or hydroxypropyl methylcellulose, or croscarmellose sodium, or sodium glycolate, or sodium alginate, or sodium lactate, or carrageenan, or pullulan, or polyethylene glycol, or polyvinyl alcohol, or polyvinylpyrrolidone, or pectin, or guar gum, or xanthan gum, as well as mixtures of these substances in various proportions.
17. The microneedle patch of claim 1 , wherein the size of the base of the microneedle is 200 μm or less.
18. The microneedle patch of claim 1 , wherein the active component is an insoluble agent and comprises polycarbonate, or polymethacrylic acid, or a copolymer of ethylene and vinyl acetate, or cured polyester resins, or polyvinyl chloride, or polyethylene or polypropylene.
19. The microneedle patch of claim 1 , wherein the microneedle matrix contains from 20 to 100 microneedles per 1 cm 2 area.
20. The microneedle patch of claim 1 , wherein the active component, is present in a mixture with the carrier bio-soluble agent in the entire volume of the microneedle matrix in an amount of a therapeutically effective dose.
21. The microneedle patch of claim 1 , wherein the active component contains a therapeutic drug, or a vaccine, or a cosmetic preparation.
22. The microneedle patch of claim 1 , wherein the substrate is provided with a plurality of planar wires that form a set of patterns around each microneedle.
23. The microneedle patch of claim 22 , wherein the set of patterns comprises a first pattern forming a circular shape around the microneedle, a second pattern forming an area facing a central axis of the microneedle, and a third pattern is placed aside of the microneedle for ground connection, and the first, second and third patterns are interconnected and the wires are not intersected with each other.
24. The microneedle patch of claim 23 , wherein the planar wires are electrically connected to an external electronic device, which provides DC and AC voltages to the microneedles and which is configured to generate an electrical charge flow.
25. A method of manufacturing the microneedle patch of claim 1 , the method comprising fabricating the microneedle matrix by filling cone-shaped wells in a mold with the mixture of the carrier bio-soluble agent with the active component, followed by steps of dehydrating, cooling, and depositing the base film, and separating an obtained part of the microneedle patch from the mold followed by its integration with a substrate at a contact surface, wherein each microneedle in the microneedle patch is made in two stages, the first stage is forming the sharp end of the microneedle by filling a first part of the wells with said mixture of the carrier bio-soluble agent with the active component, and the second stage is fabricating ft the multi-branch structure of the microneedle by filling a second part of the wells of the mold with the bio-soluble material on top of a layer of said mixture of the carrier bio-soluble agent with the active component.
26. The method of manufacturing a microneedle patch of claim 25 , wherein an amount of the mixture of the carrier bio-soluble agent with the active component is adjusted so that this mixture fills the well up to a border of the second part of the well that is for fabricating the multi-branch structure of the microneedle to be formed.
27. The method of manufacturing a microneedle patch of claim 26 , wherein a portion of the sharp end of the microneedle is in the range of 5 to 30% from a total height of the microneedle and its size on the contact surface with the multi-branch structure is less than 50% of a size of the base of the microneedle.
28. The method of manufacturing a microneedle patch of claim 25 , wherein the carrier bio-soluble agent with the active component is placed into 60-95% of a height of the wells of the mold, the mixture is aged and the dehydration process is carried out at temperature of +22° C. to +90° C. for 8 to 72 hours; for the formation of the second part, the remaining volume of the wells is filled with the bio-soluble material followed by aging and then the dehydration process at temperature of +22° C. to +90° C. for 8 to 72 hours.
29. The method of manufacturing a microneedle patch of claim 25 , wherein the method further comprises placing the substrate above the patch when the patch is in the mold followed by separation of the microneedle patch from the mold.
30. The method of manufacturing a microneedle patch of claim 25 , wherein the method further comprises integrating the substrate with the microneedle patch in a separate process by adding an adhesive layer to the contact surface.
31. The method of manufacturing a microneedle patch of claim 25 , wherein the base film is made of the bio-soluble material and the ratio of specific dissolution rates of the mixture of the carrier bio-soluble agent with the active component and the bio-soluble material is in the range from 1: 200,000 to 950,000.
32. The method of manufacturing a microneedle patch of claim 25 , wherein the base film is made of one or more layers of soluble and/or non-soluble components for further processing for integration with microelectronic devices.