CN111317911A - Novel microneedle and manufacturing method thereof - Google Patents

Abstract

The invention relates to a novel microneedle and a manufacturing method thereof, wherein the novel microneedle comprises a base and a needle body arrayed on the base, and the needle body comprises a cylindrical part connected with the base and a conical part connected with the cylindrical part; the outer surface of toper portion distributes along the axial has a plurality of standing grooves. The manufacturing method of the novel microneedle comprises the following steps: the method comprises the following steps: the base, the cylindrical part and the conical part of the needle body are produced by reverse molding through a mold; step two: a placing groove is machined on the surface of the tapered portion by laser machining. The microneedle can be loaded with various different treatment factors, the length of the microneedle is controllable, the length of the needle body is longer and can reach 5mm, and the microneedle can penetrate into a diseased position; the manufacturing method has the advantages of simple processing technology, low manufacturing cost, high reusability and good hydrophilic effect, and ensures the roughness of the surface of the microneedle; the die used in the method has good mechanical property, is not easy to damage, and has high strength and long service life.

Description

A new type of microneedle and its manufacturing method

technical field

The present invention relates to the field of microneedles, and more particularly, to a novel microneedle and a manufacturing method thereof.

Background technique

Microneedles are a third-generation transdermal drug delivery system that combines the advantages of traditional hypodermic syringes and transdermal patches. Micro-needles have the advantages of minimally invasive painless, easy to use, high safety performance, can deliver macromolecular drugs, and have good percutaneous absorption effect. effect.

The polymer microneedles used today are short in length, about 500um, and can only deliver drugs to the superficial layer of flat skin. It is not suitable for delivering drugs to surface malignant tumors with rough surface and large size. In the existing manufacturing method, a metal microneedle is used as a male mold, and a high aspect ratio microneedle mold and a microneedle with a length of 1.2 mm are prepared through two injection molding, which effectively increases the depth of drug delivery. However, for superficial malignancies with deep subcutaneous extension, it is difficult for microneedles to deliver drugs to deep affected areas. For example, nodular basal cell carcinoma can extend up to 5 mm under the skin, but there are currently no microneedles that can deliver drugs to the deep affected areas of this tumor. In addition, the existing microneedles can only be mixed and loaded with one drug, and multiple injections are required to inject multiple drugs, which is inconvenient to use.

At present, the commonly used microneedle manufacturing methods include the combination of silicon anisotropic etching process and SU-8 photolithography process to prepare silicon and photoresist composite drug-loaded microneedle molds. The three-dimensional structure of PDMS is obtained by casting and replicating with oxane (PDMS), and the preparation of microneedle mold by this method is complicated, and the mold structure is single. Since PDMS material is a very soft material, its Young's modulus is relatively small, and it is easy to be compressed and deformed, so that the service life of the microneedle mold made of PDMS material is short. In addition, silicon molds and glass molds are brittle, easily damaged during use, and have a short service life. The metal mold prepared by using the ultraviolet light source to expose the photoresist technology has high processing cost.

SUMMARY OF THE INVENTION

In order to overcome the problems that the existing microneedles in the prior art can only be loaded with one kind of medicine and the length is insufficient, and at the same time, in order to overcome the problems of high manufacturing cost of the microneedles and short service life of the preparation molds, the present invention provides a novel microneedle and its length. According to the manufacturing method, the novel microneedle can be loaded with various therapeutic factors and has sufficient length to directly deliver the therapeutic factors to the deep affected part of the tumor. The manufacturing method has simple processing technology, low manufacturing cost and long service life of the mold used.

In order to solve the above technical problems, the technical solution adopted in the present invention is: a new type of microneedle, comprising a base and a needle body arrayed on the base, and the needle body includes a cylindrical portion connected with the base and a needle body connected with the base. The conical part is connected with the cylindrical part; the outer surface of the conical part is distributed with several placement grooves along the axial direction.

Different medicines are placed in different placement slots, and different therapeutic factors can be injected into the diseased position in one injection. The tapered part is used to penetrate the patient's skin, and the tapered part can reduce the resistance to penetration of the skin.

Preferably, the diameter of the tapered portion is 100-1000 μm, the length is 1000-3000 μm, and the taper is 2-20°; the length of the cylindrical portion is 1000-3000 μm, and the center distance between the cylindrical portions is 500～1000μm. The microneedles can be of sufficient length to deliver the therapeutic agent directly to the deep affected part of the tumor.

Preferably, the needle body is made of chitosan, hyaluronic acid, gelatin, polylactic acid, and polylactic acid-glycolic acid copolymer.

Preferably, the placement groove is inclined toward the direction close to the cylindrical portion. Sloped placement slot reduces insertion resistance

Also provided is a method for manufacturing the novel microneedle, which is used to manufacture the above-mentioned novel microneedle, comprising the following steps:

Step 1: The base, the cylindrical part and the conical part of the needle body are poured out through the mold;

Step 2: Place grooves on the surface of the tapered part by laser processing.

Preferably, in the first step, the base material of the mold is a metal or alloy material with stable metal properties. The metal or alloy material can be medical titanium and titanium alloys, 316L stainless steel, medical zirconium, medical cobalt-based alloys, gold and gold alloys, silver and silver alloys, platinum and platinum alloys. The mold is made of metal material with stable properties, the mold has a long service life, and the heat transfer is fast, and it is easy to dry and form.

Preferably, in the first step, the mold base includes a groove for the mold base, a cylindrical hole for the reverse mold cylindrical portion, and a cone-shaped hole for the reverse mold cone portion. The processing method of the groove may be turning, milling, or grinding, and the depth of the groove may be 20-50% of the height of the base body. The processing method of the cylindrical hole can be mechanical processing, laser processing, electron beam processing, the mechanical processing method can be drilling, grinding hole, grinding hole; the processing method of the tapered hole can be electron beam processing, laser processing, micro EDM.

Preferably, the surface roughness of the groove is 0.05-0.2 μm. The surface roughness is small, the microneedle injection molding effect is good, the material loss is small, and the mold release is easy.

Preferably, in the second step, the power of the laser processing is 10-40%, the frequency is 10-50 KHz, and the speed is 800-1000 mm/s. Under this parameter range, the processing efficiency is high, the heat affected area is small, and a high-quality undercut can be obtained.

Preferably, in the second step, during the laser processing, the position of the laser beam is fixed, and the placement groove is processed by moving the needle body.

Compared with the prior art, the beneficial effects of the present invention are as follows: the microneedle of the present invention can be loaded with a variety of different therapeutic factors, and the length of the microneedle is controllable, the length of the needle body is long, up to 5mm, and it can penetrate deep into the diseased position. The manufacturing method of the present invention has simple processing technology, low manufacturing cost, guaranteed micro-needle surface roughness, high reusability, and good hydrophilic effect; the mold used in the method of the present invention has good mechanical properties, is not easy to damage, The mold has high strength and long service life.

Description of drawings

FIG. 1 is a schematic structural diagram of a novel microneedle of the present invention.

Among them: 1. the base; 2. the needle body; 201, the cylindrical part; 202, the conical part; 203, the placement groove.

Detailed ways

The accompanying drawings are for illustrative purposes only, and should not be construed as limitations on this patent; in order to better illustrate the present embodiment, some parts of the accompanying drawings may be omitted, enlarged or reduced, and do not represent the size of the actual product; for those skilled in the art It is understandable to the artisan that certain well-known structures and descriptions thereof may be omitted from the drawings. The positional relationships described in the drawings are only for exemplary illustration, and should not be construed as a limitation on the present patent.

The same or similar numbers in the drawings of the embodiments of the present invention correspond to the same or similar components; in the description of the present invention, it should be understood that if there are terms “upper”, “lower”, “left” and “right” The orientation or positional relationship indicated by "long" and "short" is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the indicated device or element must have a specific Therefore, the terms describing the positional relationship in the accompanying drawings are only used for exemplary illustration, and should not be construed as a limitation on this patent. For those of ordinary skill in the art, they can understand according to specific circumstances. The specific meanings of the above terms.

Below by specific embodiment, and in conjunction with accompanying drawing, the technical scheme of the present invention is further described in detail:

Example 1

As shown in FIG. 1 , an embodiment of a novel microneedle includes a base 1 and a needle body 2 arrayed on the base 1 . The needle body 2 includes a cylindrical portion 201 connected to the base 1 and a tapered portion connected to the cylindrical portion 201 . part 202; the outer surface of the tapered part 202 is distributed with a number of inclined placement grooves 203 along the axial direction, and the placement grooves 203 are inclined toward the direction close to the cylindrical part.

Specifically, the diameter of the tapered portion 202 is 500 μm, the length is 3000 μm, and the taper is 9.5°; the length of the cylindrical portion 201 is 2000 μm, and the center-to-center distance between the cylindrical portions 201 is 500 μm. The microneedles can be of sufficient length to deliver the therapeutic agent directly to the deep affected part of the tumor.

The material of the needle body 2 is gelatin.

The working principle or working flow of the present invention: different medicines are placed in different placement slots, and different therapeutic factors can be injected into the diseased position in one injection. The tapered part is used to penetrate the patient's skin, and the tapered part can reduce the resistance to penetration of the skin.

Beneficial effects of this embodiment: the microneedle of the present invention can be loaded with a variety of different therapeutic factors, and the length of the microneedle is controllable, the length of the needle body can reach 5 mm, and it can penetrate deep into the diseased position.

Example 2

The difference between this embodiment and Embodiment 1 is that the diameter of the tapered portion 202 is 1000 μm, the length is 2000 μm, and the taper is 15°; the length of the cylindrical portion 201 is 3000 μm, and the center distance between the cylindrical portions 201 is 1000 μm. The rest of the features and working principles are the same as in Example 1.

Example 3

A method for manufacturing a novel microneedle, which is used to manufacture the novel microneedle of Example 1 or Example 2, comprising the following steps:

Step 1: The base, the cylindrical part and the conical part of the needle body are poured out through the mold;

Step 2: Place grooves on the surface of the tapered part by laser processing. The power of laser processing is 15%, the frequency is 25KHz, and the speed is 800mm/s.

Specifically, the base material of the mold is a metal or alloy material with stable metal properties, specifically a titanium alloy. The mold is made of metal material with stable properties, the mold has a long service life, and the heat transfer is fast, and it is easy to dry and form.

Wherein, the mold base includes a groove for the mold base, a cylindrical hole for the reverse mold cylindrical portion, and a cone-shaped hole for the reverse mold cone portion. The processing method of the groove is grinding, and the surface roughness of the groove is processed to 0.05 μm, and the depth of the groove can be 30% of the height of the substrate. The processing method of the cylindrical hole is grinding hole; the processing method of the tapered hole can be electron beam processing. The surface roughness of the groove is small, the microneedle injection molding effect is good, the material loss is small, and the mold release is easy.

Specifically, in step 2, during the laser processing, the position of the laser beam is fixed, and the placement groove is processed by moving the needle body.

The beneficial effects of this embodiment: the manufacturing method of the present invention has simple processing technology, low manufacturing cost, guaranteed microneedle surface roughness, high reusability, and good hydrophilic effect; the mold used in the method of the present invention has good Mechanical properties, not easy to damage, high mold strength, long service life.

Example 4

A method for manufacturing a novel microneedle, which is used to manufacture the novel microneedle of Example 1 or Example 2, comprising the following steps:

Step 1: The base, the cylindrical part and the conical part of the needle body are poured out through the mold;

Step 2: Place grooves on the surface of the tapered part by laser processing. The power of laser processing is 35%, the frequency is 45KHz, and the speed is 1000mm/s.

Specifically, the base material of the mold is a metal or alloy material with stable metal properties, specifically a titanium alloy.

Wherein, the mold base includes a groove for the mold base, a cylindrical hole for the reverse mold cylindrical portion, and a cone-shaped hole for the reverse mold cone portion. The processing method of the groove is grinding, and the roughness of the groove surface is processed to 0.12 μm, and the groove depth can be 40% of the height of the substrate. The processing method of the cylindrical hole is grinding hole; the processing method of the tapered hole can be electron beam processing.

Specifically, in step 2, during the laser processing, the position of the laser beam is fixed, and the placement groove is processed by moving the needle body.

Obviously, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, rather than limiting the embodiments of the present invention. For those of ordinary skill in the art, changes or modifications in other different forms can also be made on the basis of the above description. There is no need and cannot be exhaustive of all implementations here. Any modifications, equivalent replacements and improvements made within the spirit and principle of the present invention shall be included within the protection scope of the claims of the present invention.

Claims (10)

1. A novel microneedle comprising a base (1) and a needle body (2) arrayed on the base (1), characterized in that the needle body (2) comprises a base (1) connected to the base (1). A cylindrical portion (201) and a conical portion (202) connected to the cylindrical portion (201); the outer surface of the conical portion (202) is axially distributed with several placement grooves (203). 2 . The novel microneedle according to claim 1 , wherein the diameter of the tapered portion ( 202 ) is 100-1000 μm, the length is 1000-3000 μm, and the taper is 2-20°; the cylinder The length of the parts (201) is 1000-3000 μm, and the center-to-center distance between the cylindrical parts (201) is 500-1000 μm. 3 . The novel microneedle according to claim 1 , wherein the needle body ( 2 ) is made of chitosan, hyaluronic acid, gelatin, polylactic acid, and polylactic acid-glycolic acid copolymer. 4 . 4 . The novel microneedle according to claim 1 , wherein the placement groove ( 203 ) is inclined toward the direction of the cylindrical portion ( 201 ). 5 . 5. A method for manufacturing a novel microneedle, characterized in that, for manufacturing the novel microneedle according to any one of claims 1-4, comprising the following steps: Step 1: The base, the cylindrical part and the conical part of the needle body are poured out through the mold; Step 2: Place grooves on the surface of the tapered part by laser processing. 6 . The method for manufacturing a novel microneedle according to claim 5 , wherein, in the first step, the base material of the mold is an alloy material with stable metal properties. 7 . 7 . The method for manufacturing a novel microneedle according to claim 5 , wherein in the first step, the mold base comprises a groove for the mold base and a cylindrical hole for the mold cylindrical portion. 8 . and a tapered hole for the reverse mold taper. 8 . The method for manufacturing a novel microneedle according to claim 7 , wherein the surface roughness of the groove is 0.05-0.2 μm. 9 . 9 . The manufacturing method of a novel microneedle according to claim 5 , wherein in the second step, the power of the laser processing is 10-40%, the frequency is 10-50KHz, and the speed is 800 ~1000mm/s. 10 . The manufacturing method of a novel microneedle according to claim 5 , wherein in the second step, during the laser processing, the position of the laser beam is fixed, and the placement of the groove is carried out by moving the needle body. 11 . processing.

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