Novel preparation device and method of hollow microneedle

Abstract

The invention relates to the technical field of hollow microneedle preparation, in particular to a novel preparation device and method for a hollow microneedle. The hollow microneedle manufacturing platform is obtained through piercing combination of the male die, the guide plate and the female die, and the platform can be used for casting through-hole microneedles in one step. Compared with a shell-structure micro-needle manufactured by a traditional micro-forming method, the through-hole micro-needle is better in mechanical property, and the cuticle is more easily punctured; meanwhile, the manufacturing platform can be repeatedly used for producing the hollow microneedles for multiple times, and the technical requirement for low cost is met; by adding different biocompatible polymer solutions, the platform can be suitable for producing hollow microneedles made of different materials; the hollow microneedle patches with different shapes can be produced by changing the concave shape of the female die.

Description

Technical Field

[0001] The present invention relates to the technical field of hollow microneedle preparation, and more specifically to a novel preparation device and method for hollow microneedles. Background Art

[0002] Microneedles are an effective transdermal drug delivery method. For drugs such as proteins and peptides that become ineffective when taken orally, the use of microneedles will be less invasive than traditional injections, reducing the pain experienced by patients. However, the difficulty in preparing hollow microneedles has limited their widespread application. How to manufacture hollow microneedles at low cost and in large quantities has become a core problem.

[0003] At present, the mainstream methods for preparing hollow microneedles include 3D printing, photolithography, micromolding, etc. Among them, photolithography is very expensive and requires special equipment, which makes it difficult to promote commercialization. In addition, photolithography is often used to prepare silicon microneedles, which are brittle and have poor biocompatibility; 3D printing materials are usually resins, ceramics, and metals, which are relatively expensive compared to polymer materials; micromolding methods such as centrifugal method and sandwich method often prepare shell microneedles, which need to be pierced through the shell again in the future to achieve through-holes, which increases the cumbersome preparation steps, and the mechanical properties of the shell microneedles are not strong, the structural support is insufficient, and they need to be processed before they can be inserted into the human body. Summary of the invention

[0004] The present invention provides a novel preparation device and method for hollow microneedles, aiming to realize low-cost, large-scale production of microneedle arrays with hollow through holes of various materials.

[0005] The above purpose is achieved through the following technical solutions:

[0006] A novel method for preparing hollow microneedles comprises the following steps:

[0007] Step 1: A groove and a depression are formed on the female mold, wherein the depression is located in the groove, and a protrusion is formed on the male mold;

[0008] Step 2: Make the protrusion pass through the female mold first and then through the recess, and the protrusion and the recess are coaxially arranged;

[0009] Step 3: Add the solution for making microneedles into the grooves and depressions, and peel off the solution after the solution solidifies to obtain hollow microneedles.

[0010] Before performing step two, a guide plate is set between the female mold and the male mold, and a through hole is set on it. One opening end of the through hole is a wide opening, and the other opening end is a narrow opening. The through hole, the recess and the protrusion are aligned to achieve a coaxial arrangement. The through hole is used to allow the protrusion of the male mold to first enter from the wide opening, then pass out from the narrow opening, and then penetrate into the female mold and then pass through the recess.

[0011] The depressions and protrusions are arranged in arrays.

[0012] The recesses, through holes and protrusions are all arranged in an array.

[0013] The material of the female mold is polydimethylsiloxane or silicone.

[0014] The material of the solution used to make microneedles is a high molecular polymer.

[0015] A novel preparation device for hollow microneedles is used, comprising a frame platform with an upper opening and a bottom surface, wherein two clamps for feeding are arranged on the frame platform through threaded cooperation, and the movement directions of the two clamps are perpendicular.

[0016] The female mold, guide plate and male mold are the preparation platform of the hollow microneedle, and after being placed in sequence, the walls on all sides can be aligned to place the preparation platform of the hollow microneedle in the frame, and the lower end surface of the preparation platform is fitted with the bottom surface of the frame. One of the clamps pushes the preparation platform so that the female mold, guide plate and male mold are simultaneously fitted on the inner wall surface of the frame facing one of the clamps, and then another clamp is used to push the male mold so that the end surface of the female mold with the groove is fitted on the inner wall surface of the frame facing the other clamp, and the protrusion is completed by first passing through the female mold and then passing through the depression.

[0017] The fixture is L-shaped and slidably connected to the frame. The vertical structure of the fixture is inside the frame and is threadedly connected to the frame using studs. The studs are used to push the vertical structure of the fixture to complete the feeding of the fixture.

[0018] The stud is rotated to move away from the fixture, and the fixture is moved away from the hollow microneedle preparation platform, so that the hollow microneedle preparation platform can be taken out from the frame.

[0019] The beneficial effects of the novel preparation device and method of hollow microneedles of the present invention are:

[0020] Through the combination of the male mold, the guide plate, and the female mold, a hollow microneedle manufacturing platform is obtained, which can cast through-hole microneedles in one step. Compared with the shell structure microneedles manufactured by the traditional micro-molding method, the through-hole microneedles have better mechanical properties and are easier to pierce the stratum corneum; at the same time, the manufacturing platform can be reused many times to produce hollow microneedles many times, meeting the technical requirements of low cost; by adding different biocompatible polymer solutions, the platform can be used to produce hollow microneedles of different materials; by changing the groove and depression shape of the female mold, it can be used to produce hollow microneedle patches with different shapes. The patch structure shape of the hollow microneedle patch includes a base film and a hollow microneedle structure formed on the base film, wherein the shape of the base film is determined by the groove, and the shape of the microneedle is determined by the depression and protrusion. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 A perspective view showing a novel preparation device for hollow microneedles;

[0022] Figure 2 A schematic diagram of the frame stage is shown;

[0023] Figure 3 A schematic diagram of the structure of the first top block is shown;

[0024] Figure 4 A schematic diagram of the structure of the negative mold is shown;

[0025] Figure 5 A schematic diagram of the structure of the guide plate is shown;

[0026] Figure 6 A schematic diagram of the structure of the male mold is shown;

[0027] Figure 7 A schematic diagram of the structure of the fabrication platform for hollow microneedles is shown.

[0028] In the figure: frame 1, first through groove 101, second through groove 102, first threaded hole 103, second threaded hole 104, first top block 2, top block inner end surface 201, second top block 3, first stud 4, second stud 5, female mold 6, recess 601, female mold bottom surface 602, guide plate 7, through hole 701, male mold 8, protrusion 801, male mold top surface 802, hollow microneedle preparation platform 9. DETAILED DESCRIPTION

[0029] A novel preparation device for hollow microneedles, e.g. Figures 1 to 3 , including a frame 1, a first through slot 101 is provided at the rear end of the frame 1, a first top block 2 located in the first through slot 101 is inserted on the frame 1, and the first top block 2 slides forward and backward on the frame 1. A first threaded hole 103 is provided at the rear end of the frame 1, and a first stud 4 is screwed into the first threaded hole 103, so that the first stud 4 is connected to the frame 1 through threaded cooperation. The first stud 4 is used to abut against the rear end of the first top block 2, and the first stud 4 is rotated to push the first top block 2 to move forward.

[0030] Similarly, the left end of the frame 1 is provided with a second through slot 102, and the frame 1 is plugged with a second top block 3 located in the second through slot 102, so that the second top block 3 can slide left and right on the frame 1. The left end of the frame 1 is provided with a second threaded hole 104, and a second stud 5 is screwed into the second threaded hole 104, so that the second stud 5 is connected to the frame 1 through threaded cooperation. The second stud 5 is used to abut against the left end of the second top block 3, and the second stud 5 is rotated to push the second top block 3 to move left and right.

[0031] The first top block 2 and the second top block 3 have the same structure, which is L-shaped, and the first top block 2 and the second top block 3 facing the inside of the frame 1 are marked as top block inner end surfaces 201.

[0032] Further, the hollow microneedle preparation platform 9 is also included. The hollow microneedle preparation platform 9 is for example Figures 4 to 7 , including a female mold 6, a recess 601 is arranged at the upper end of the female mold 6, and the recess has the shape characteristics of the microneedle model. The recess 601 can be evenly distributed at the upper end of the female mold 6 to form an array. The material of the female mold 6 is polydimethylsiloxane or silicone. The inner diameter of the recess 601 decreases from top to bottom. The lower end surface of the female mold 6 is recorded as the female mold bottom surface 602. The surfaces adjacent to the female mold bottom surface 602 are four vertical outer wall surfaces around the female mold 6.

[0033] A guide plate 7 is provided below the female mold 6, and a through hole 701 is provided on the guide plate 7. The bottom of the through hole 701 is a wide opening, and the top is a narrow opening. The through holes 701 can be evenly distributed on the female guide plate 7 in an array, and the inner diameter of the through holes 701 increases from top to bottom. The positions of the through holes 701 and the recesses 601 correspond one to one in the longitudinal direction, and each through hole 701 corresponds to one recess 601.

[0034] A male mold 8 is disposed below the guide plate 7, and a protrusion 801 is fixedly connected to the upper end of the male mold 8. The protrusions 801 can be evenly distributed at the upper end of the male mold 8 to form an array. The upper end surface of the male mold 8 is recorded as the male mold top surface 802, and the lower end surface of the male mold 8 is recorded as the male mold bottom surface 803. The protrusions 801 correspond to the through holes 701 in the longitudinal direction, and each protrusion 801 corresponds to a through hole 701.

[0035] When the protrusion 801 of the male mold 8 enters from the thick opening to pass through the through hole 701 from bottom to top, the narrow opening will restrict the puncture point and puncture direction of the protrusion 801; so that each protrusion 801 passes through the female mold 6 from bottom to top and passes through a recess 601.

[0036] Preferably, a groove is provided at the upper end of the female mold 6, and the through hole 701 is located in the groove. The groove is used to add a solution for manufacturing microneedles so that the solution enters the recess 601. On the other hand, the protrusion 801 closes one end of the recess 601 facing the guide plate 7, and the protrusion 801 closes the narrow mouth of the through hole 701 to prevent the solution from further entering the position of the female mold 6 punctured by the protrusion 801 and the guide plate 7.

[0037] For example Figure 1When the hollow microneedle preparation platform 9 is used, it is placed in the frame 1, and the concave side of the female mold 6 is attached to the front end face 105 of the inner wall of the frame 1, and any two adjacent vertical outer wall faces of the female mold 6 are attached to the right end face 106 of the inner wall of the frame 1 and the inner bottom face 107 of the frame 1, and the inner end face 201 of the second top block 3 is attached to the female mold 6, the guide plate 7 and the male mold 8, so as to complete the positioning of the hollow microneedle preparation platform 9, and at the same time, the bottom face 803 of the male mold is attached to the inner end face 201 of the top block on the first top block 2, and the first top block 2 pushes the male mold 8 forward, so that the female mold 6, the guide plate 7 and the male mold 8 are attached, and the protrusion 801 passes through the through hole 701 and the concave 601. By rotating the first stud 4 and the second stud 5, the first top block 2 and the second top block 3 are separated from the hollow microneedle preparation platform 9, and then the hollow microneedle preparation platform is taken out of the frame 1. Finally, the solution for making microneedles is added to the hollow microneedle preparation platform 9, which may be one or more solutions of polylactic acid-glycolic acid copolymer, hyaluronic acid, photocurable gelatin or chitosan, and then peeled off after curing to obtain hollow microneedles, and the hollow microneedle preparation platform 9 can continue to be used. The solution for making microneedles may also be other solutions, and the specific shape structure of the hollow microneedle patch may also be a variety of shapes. This is not to limit the invention in other forms. Any technician familiar with this profession may use the technical content disclosed above to change or modify it into an equivalent embodiment of equivalent changes. However, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the technical solution of the present invention still belongs to the protection scope of the present invention.

Claims

1. A novel method for preparing hollow microneedles, characterized in that: The following steps are involved: Step 1: A groove and a depression (601) are formed on the female mold (6), the depression (601) is located in the groove, and a protrusion (801) is formed on the male mold (8); Step 2: Make the protrusion (801) pass through the female mold (6) first and then pass through the recess (601), and the protrusion (801) and the recess (601) are coaxially arranged; Step 3: Add a solution for making microneedles into the grooves and depressions (601), and peel off the solution after the solution solidifies to obtain hollow microneedles.

2. According to the novel preparation method of hollow microneedles described in claim 1, before performing step 2, a guide plate (7) is arranged between the female mold (6) and the male mold (8), and a through hole (701) is arranged on the guide plate. One opening end of the through hole (701) is a thick opening, and the other opening end is a thin opening. The through hole (701), the recess (601) and the protrusion (801) are aligned to achieve a coaxial arrangement. The through hole (701) is used to allow the protrusion (801) of the male mold (8) to first enter from the thick opening, then pass out from the thin opening, and then penetrate into the female mold (6) and then pass through the recess (601).

3. According to the novel method for preparing hollow microneedles according to claim 1, the depressions (601) and the protrusions (801) are arranged in an array.

4. According to the novel method for preparing hollow microneedles according to claim 2, the depressions (601), through holes (701) and protrusions (801) are all arranged in an array.

5. According to the novel method for preparing hollow microneedles according to claim 1, the material of the female mold (6) is polydimethylsiloxane or silica gel.

6. According to the novel method for preparing hollow microneedles according to any one of claims 1 to 5, the material of the solution for making the microneedles is a high molecular polymer.

7. According to the novel method for preparing hollow microneedles as described in claim 2, a novel device for preparing hollow microneedles is used, comprising a frame (1) with an upper opening and a bottom surface, and two clamps for feeding by threaded engagement are arranged on the frame (1), and the movement directions of the two clamps are perpendicular.

8. According to the novel preparation method of hollow microneedles described in claim 7, the female mold (6), the guide plate (7) and the male mold (8) are the preparation platform (9) of the hollow microneedles, and the walls around them can be aligned after being placed in sequence. The preparation platform (9) of the hollow microneedles is placed in the frame (1), and the lower end surface of the preparation platform (9) is in contact with the bottom surface of the frame (1). One of the clamps pushes the preparation platform (9) so that the female mold (6), the guide plate (7) and the male mold (8) are simultaneously in contact with the inner wall surface of the frame (1) facing the one of the clamps, and then another clamp is used to push the male mold (8) so that the end surface of the female mold (6) with the groove is in contact with the inner wall surface of the frame (1) facing the other clamp, and the protrusion (801) first passes through the female mold (6) and then passes through the depression (601).

9. According to the novel preparation method of hollow microneedles described in claim 8, the clamp is L-shaped and slidably connected to the frame (1), the vertical structure of the clamp is inside the frame (1), and is threadedly connected to the frame (1) using a stud, and the stud is used to push the vertical structure of the clamp to complete the feeding of the clamp.

10. According to the novel method for preparing hollow microneedles according to claim 9, the preparation platform (9) of the hollow microneedles can be taken out from the frame (1) by rotating the stud so that the stud is away from the fixture and the fixture is moved away from the preparation platform (9) of the hollow microneedles.

Images