Preparation method and mold of hollow microneedle

Abstract

The invention relates to the technical field of hollow microneedles, in particular to a preparation method of a hollow microneedle and a mold of the hollow microneedle. The female die and the limiting plate are clamped through the positioning device, the relative positions of the female die and the limiting plate are finely adjusted, then a guide wire is used for penetrating, the hollow microneedle manufacturing die is obtained, and the die can be used for casting hollow microneedles in one step. The mold can be repeatedly used, all procedures and materials are low in price and easy to obtain, and the manufacturing cost of the hollow microneedle is greatly reduced; by changing the shape of the recess in the female die, the hollow microneedles with different shapes and different sizes can be manufactured, and the preparation of the hollow microneedles with large length-diameter ratio can be realized; the hollow microneedles with different holes can be prepared by changing the size and the shape of the guide wire; by adding different microneedle preparation solutions, the platform can be suitable for producing hollow microneedles made of different materials; in conclusion, the preparation method of the hollow microneedle has the characteristics of low cost, universality and high individuation.

Description

Technical Field

[0001] The invention relates to the technical field of hollow microneedles, and more particularly to a preparation method of the hollow microneedle and a mold thereof. Background Art

[0002] Microneedles can easily pierce the stratum corneum of the skin to form a drug channel, and deliver drugs without gastrointestinal metabolism or first-pass effect in the liver. Microneedles are classified into solid microneedles, hollow microneedles, dissolving microneedles, etc. Among them, hollow microneedles are microneedles with hollow channels, which can achieve large-dose drug delivery compared with other types of microneedles, which makes them have broad application prospects in the medical field. However, the preparation of hollow microneedles is difficult, and the existing preparation methods include photolithography, 3D printing, dripping, centrifugation, etc. Among them, photolithography is expensive, the process is complex, and the material limitations are large; 3D printing also limits the materials that can be used to prepare hollow microneedles, and the equipment cost is relatively high; the dripping method cannot produce microneedles with controllable appearance and morphology, and the outer boundary of the microneedle is determined by the tension of the liquid material before solidification, and cannot be designed artificially; the internal pores of the hollow microneedles prepared by the centrifugation method are large, and the shape of the microneedle is close to the shell layer, resulting in poor mechanical properties of the microneedle, which greatly limits further application. Therefore, it is of great significance to develop low-cost preparation methods and related molds for hollow microneedles that have controllable shapes and internal pores and are compatible with multiple materials. Summary of the invention

[0003] The present invention provides a method for preparing a hollow microneedle and a mold thereof, aiming to realize a hollow microneedle array with low cost, controllable morphology and structure and multiple materials.

[0004] The above purpose is achieved through the following technical solutions:

[0005] A method for preparing a hollow microneedle comprises the following steps:

[0006] Step 1: a hole is formed on the limiting plate, a depression and a microneedle groove are formed on the female mold, and the microneedle groove is located in the depression;

[0007] Step 2: Use a guide wire to penetrate from one end of the hole on the limiting plate, and out from the other end of the hole, and then penetrate into the female mold from the side away from the depression. After puncture, the guide wire occupies the microneedle groove on the female mold, and the liquid material used for preparing hollow microneedles is injected into the depression and microneedle groove of the female mold. After curing, demolding is performed to obtain hollow microneedles.

[0008] The inner diameter of the hole of the limiting plate gradually decreases at one end close to the female mold.

[0009] The method for preparing the negative mold comprises the following steps:

[0010] Step 1: a microneedle model, including a base and a protrusion fixed to the upper end of the base, is immersed in a mold material;

[0011] Step 2: After the mold material is solidified, the microneedle model is taken out from the solidified mold material;

[0012] Step 3: The solidified mold material retains the depression formed by the base and the microneedle groove formed by the protrusion, and the solidified mold model is the negative mold.

[0013] The length of the protrusions ranges from 20 to 2000um.

[0014] The mold material is polydimethylsiloxane or silicone.

[0015] Changing the shape of the protrusions on the microneedle model can be used to prepare hollow microneedles of different shapes, thereby changing the shape and size of the microneedle grooves in the female mold depression.

[0016] The liquid material is made of high molecular polymer.

[0017] A positioning device using a hollow microneedle;

[0018] The positioning device of the hollow microneedle includes a base, on which a clamping mechanism is arranged, the clamping mechanism includes two clamps capable of adjusting the spacing; two clamping mechanisms are arranged, and the clamp movement directions of the two clamping mechanisms are intersecting; the clamp is used to clamp the outer wall surface of the limit plate or the female mold.

[0019] The two clamping mechanisms are spaced apart in the longitudinal direction.

[0020] The side lengths of the limiting plate and the female mold are the same, so that the peripheral outer wall surfaces of the limiting plate and the female mold are located on a virtual tetrahedron.

[0021] The beneficial effects of the preparation method of a hollow microneedle and the mold thereof of the present invention are:

[0022] The female mold and the limiting plate are clamped by the positioning device and the relative positions of the two are finely adjusted, and then a guide wire is used to penetrate to obtain a hollow microneedle manufacturing mold, which can cast hollow microneedles in one step. The mold can be reused many times, and each process and material is inexpensive and easy to obtain, which greatly reduces the manufacturing cost of hollow microneedles;

[0023] By changing the shape of the depression in the female mold, hollow microneedles of different shapes and sizes can be manufactured, and the preparation of hollow microneedles with a large aspect ratio can be achieved;

[0024] By changing the size and shape of the guide wire, hollow microneedles with different pores can be prepared;

[0025] By adding different microneedle preparation solutions, the platform can be applied to the production of hollow microneedles made of different materials; in summary, the hollow microneedle preparation method is low-cost, universal, and highly personalized. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 is a schematic diagram of the structure of the base;

[0027] Figure 2 A schematic diagram of fixing a preparation mold of a hollow microneedle to a positioning device of the hollow microneedle;

[0028] Figure 3 A three-dimensional diagram of a mold for preparing hollow microneedles;

[0029] Figure 4 for Figure 2 Inverted top view;

[0030] Figure 5 is a schematic diagram of the structure of the first slider and the second slider;

[0031] Figure 6 is a schematic diagram of the structures of the first clamp, the second clamp, the third clamp and the fourth clamp;

[0032] Figure 7 is a schematic diagram of the structures of the first rotational joint, the second rotational joint, the third rotational joint and the fourth rotational joint;

[0033] Figure 8 It is a schematic diagram of the structure of the first clamping joint and the second clamping joint;

[0034] Fig. 9 It is a schematic diagram of the structures of the first side support, the second side support, the third side support and the fourth side support;

[0035] Fig.10 It is a structural schematic diagram of a limiting plate;

[0036] Fig.11 It is a schematic diagram of the structure of the negative mold;

[0037] Fig.12 is a schematic diagram of the structure of the guide wire;

[0038] Fig.13 Schematic diagram of the structure of the microneedle model;

[0039] Fig.14 Schematic diagram of the guide wire puncture limit plate and the female mold.

[0040] In the figure: base 1; first through slot 101; second through slot 102; third through slot 103; fourth through slot 104; first placement slot 105; second placement slot 106; first through hole 107; second through hole 108; third through hole 109; fourth through hole 110; first slider 2a; second slider 2b; first clamp 3a; second clamp 3b; third clamp 3c; fourth clamp 3d; first clamping joint 5a; second clamping joint 5b; first clamp clamping knob 6a; second clamp clamping knob 6b; first side support 7a; second side support 7b; third side support 7c and fourth side support 7d; first bolt 8a; second bolt 8b; first nut 9a; second nut 9b; first fine-tuning knob 10a; second fine-tuning knob 10b; third fine-tuning knob 10c; fourth fine-tuning knob 10d; limit plate 11; female mold 12; guide wire 13. DETAILED DESCRIPTION

[0041] The microneedle model includes a base and a protrusion fixed to the upper end of the base, and the length of the protrusion is between 20 and 2000 um.

[0042] Preparation method of female mold 12:

[0043] Step 1: Immerse the microneedle model in a molding material; the molding material includes polydimethylsiloxane or silicone;

[0044] Step 2: After the mold material is solidified, the microneedle model is taken out from the solidified mold material;

[0045] Step 3: After the microneedle model is removed from the solidified mold material, the solidified mold material retains a depression formed by the base of the microneedle model, and the depression retains a microneedle groove with microneedle shape characteristics formed by the protrusion. The solidified mold model is the negative mold 12. Fig.11 The upper end of the female mold 12 has a depression, and a microneedle groove is formed in the depression.

[0046] Among them, changing the shape of the protrusion on the microneedle model, thereby changing the shape and size of the microneedle groove in the depression of the female mold 12, can be used to prepare hollow microneedles of different shapes.

[0047] The preparation mold of the hollow microneedle includes a limiting plate 11, a hole is arranged on the limiting plate 11, and a female mold 12 is arranged above the limiting plate 11. The hole on the limiting plate 11 and the microneedle groove on the female mold 12 can overlap partially or completely. Fig.10 In the example, the inner diameter of the hole of the limiting plate 11 increases from top to bottom. Fig.14When the guide wire 13 punctures, either the limiting plate 11 or the female mold 12 can be at the bottom. When the limiting plate 11 is at the bottom, use the guide wire 13 to penetrate from one end of the thicker hole on the limiting plate 11, and exit from one end of the thinner hole, and then penetrate into the female mold 12, the microneedle groove of the female mold 12, and finally penetrate out of the depression of the female mold 12. After puncture, the guide wire 13 occupies the microneedle groove on the female mold 12. Since the female mold 12 is elastic, the female mold 12 will tighten the guide wire 13 after the guide wire 13 is penetrated, and the two are in close contact. Therefore, the liquid material is still in the depression of the female mold 12 and the microneedle groove, and will not continue to penetrate further along the guide wire 13 toward the direction of the limiting plate 11. After puncture, the depression of the female mold 12 can be facing upwards, so that the liquid material prepared by the hollow microneedle can be poured into the depression. On the contrary, Fig.14 After the schematic structure in FIG. 1 is turned over, the guide wire 13 is punctured from top to bottom.

[0048] The method for preparing the hollow microneedle comprises the following steps:

[0049] Step 1: fix the relative positions of the limiting plate 11 and the female mold 12 to allow the guide wire 13 to puncture;

[0050] Step 2: injecting liquid material for preparing hollow microneedles into the depression of the female mold 12 and the microneedle groove, and demoulding after solidification to obtain hollow microneedles.

[0051] The relative positions of the limiting plate 11 and the female mold 12 are maintained by a positioning device of the hollow microneedle.

[0052] Specifically, the positioning device of the hollow microneedle, combined with Figures 1 to 3 , including a base 1, a first through slot 101 is provided on the wall at the left end of the base 1, a first slider 2a is inserted into the first through slot 101, so that the first slider 2a can slide left and right relative to the base 1. The front and rear ends of the left part of the base 1 are raised to form a first convex wall, and the first through hole 107 and the second through hole 108 are respectively provided on the two first convex walls, one in front and one in the back. The first fine-tuning knob 10a and the second fine-tuning knob 10b are respectively placed in the first through hole 107 and the second through hole 108, and the first fine-tuning knob 10a and the second fine-tuning knob 10b are fixed to the base 1. By rotating the first fine-tuning knob 10a and the second fine-tuning knob 10b according to different rotation directions, the first slider 2a can be clamped or loosened to fix or cancel the relative position of the first slider 2a and the base 1.

[0053] Similarly, a second through slot 102 is provided on the wall at the rear end of the base 1, and a second slider 2b is inserted into the second through slot 102, so that the second slider 2b can slide forward and backward relative to the base 1. The left and right ends of the rear part of the base 1 are raised to form a second convex wall, and a third through hole 109 and a fourth through hole 110 are respectively provided on the left and right second convex walls. A third fine-tuning knob 10c and a fourth fine-tuning knob 10d are respectively placed in the third through hole 109 and the fourth through hole 110, and the third fine-tuning knob 10c and the fourth fine-tuning knob 10d are fixed to the base 1. By rotating the third fine-tuning knob 10c and the fourth fine-tuning knob 10d according to different rotation directions, the second slider 2b can be clamped or loosened to fix or cancel the relative position of the second slider 2b and the base 1.

[0054] The first slider 2a and the second slider 2b have the same structure. For ease of description, refer to Figure 4 , taking the first slider 2a as an example. The first slider 2a comprises a horizontal body 201, a vertical body 202 fixed to the horizontal body 201 and located in the base 1, a slide rail 203 is arranged on the side of the vertical body 202 facing the base 1, and a through hole 204 communicating with the slide rail 203 is arranged on the vertical body 202.

[0055] The third clamp 3c and the fourth clamp 3d are slidably connected in the slide rail 203 on the first slider 2a; the first clamp 3a and the second clamp 3b are slidably connected in the slide rail 203 on the second slider 2b. The first clamp clamping knob 6a is installed in the through hole 204 on the first slider 2a, and the second clamp clamping knob 6b is installed in the through hole 204 on the second slider 2b, so that the first clamp clamping knob 6a and the second clamp clamping knob 6b are respectively rotatably connected to the two vertical bodies 202, and the first clamp clamping knob 6a is fixedly connected to the first clamp clamping knob 6a, and the two ends of the first clamping joint 5a are respectively hinged to one end of the third rotating joint 4c and one end of the fourth rotating joint 4d, and the other end of the third rotating joint 4c and the other end of the fourth rotating joint 4d are respectively hinged to the fourth clamp 3d and the third clamp 3c. The base 1 is provided with a first placement slot 105 and a second placement slot 106 , and the first placement slot 105 and the second placement slot 106 are respectively used for the first clamp clamping knob 6 a and the second clamp clamping knob 6 b to be placed and passed through.

[0056] The second clamping joint 5b is fixedly connected to the clamping knob 6b of the second clamp, and the two ends of the second clamping joint 5b are respectively hinged to one end of the first rotating joint 4a and one end of the second rotating joint 4b, and the other end of the third rotating joint 4c and the other end of the fourth rotating joint 4d are respectively hinged to the fourth clamp 3d and the third clamp 3c.

[0057] The first clamp clamping knob 6a is rotated to adjust the distance between the fourth clamp 3d and the third clamp 3c, and the second clamp clamping knob 6b is rotated to adjust the distance between the first clamp 3a and the second clamp 3b. The first clamp clamping knob 6a and the second clamp clamping knob 6b have the same structure, both of which are bolt and nut assemblies. The nut is screwed on the bolt, and the nut is rotated to abut against the base 1 to prevent the bolt connected to the base 1 from rotating. The damping principle can also be used, and the first clamp clamping knob 6a and the second clamp clamping knob 6b are connected to the base 1 in a damping rotational connection.

[0058] A third through groove 103 is provided at the right end of the base 1, and a first limiting bolt 8a is inserted into the third through groove 103. The first limiting bolt 8a abuts against the first slider 2a. A first nut 9a is connected to the first limiting bolt 8a through threaded cooperation. The first nut 9a abuts against the right end of the inner wall of the base 1, and the first limiting bolt 8a abuts against the first slider 2a, so that the first slider 2a fits against the inner wall of the base 1.

[0059] A fourth through slot 104 is provided at the front end of the base 1, into which a second bolt 8b is inserted. The second bolt 8b abuts against the left end of the second slider 2b. A second nut 9b is threadedly connected to the second bolt 8b, and the second nut 9b abuts against the right end of the inner wall of the base 1.

[0060] The first slider 2a and the second slider 2b are arranged in a staggered manner, and the first slider 2a is higher than the second slider 2b.

[0061] The first clamp 3a, the second clamp 3b, the third clamp 3c and the fourth clamp 3d are respectively fixedly connected with a first side bracket 7a, a second side bracket 7b, a third side bracket 7c and a fourth side bracket 7d.

[0062] Preferably, the first side support 7a, the second side support 7b, the first clamp 3a and the second clamp 3b are all in contact with the female mold 12; the third side support 7c, the fourth side support 7d, the third clamp 3c and the fourth clamp 3d are all in contact with the female mold 12;

[0063] The third clamp 3 c and the fourth clamp 3 d are both in contact with the limiting plate 11 .

[0064] Among them, the solution for making microneedles can also be various solutions such as polylactic acid-glycolic acid copolymer, hyaluronic acid, photocurable gelatin, chitosan, etc., or other solutions that can prepare microneedle solutions. The specific shape structure of the hollow microneedle patch can 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 with 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 method for preparing a hollow microneedle, comprising the following steps: Step 1: a hole is formed on the limiting plate (11), a depression and a microneedle groove are formed on the female mold (12), and the microneedle groove is located in the depression; Step 2: Use a guide wire (13) to puncture the limiting plate (11) and the female mold (12) in sequence from one end of the hole on the limiting plate (11). After puncture, the guide wire (13) is located in the microneedle groove on the female mold (12), and liquid material for preparing hollow microneedles is injected into the female mold (12). After curing, the material is demoulded to obtain a hollow microneedle.

2. According to the method for preparing hollow microneedles according to claim 1, the inner diameter of the hole of the limiting plate (11) gradually decreases at the end close to the female mold (12).

3. The method for preparing the hollow microneedle according to claim 2, wherein the method for preparing the negative mold (12) comprises the following steps: Step 1: a microneedle model, including a base and a protrusion fixed to the upper end of the base, is immersed in a mold material; Step 2: After the mold material is solidified, the microneedle model is taken out from the solidified mold material; Step 3: The solidified reverse mold material retains a depression formed by the base, and the depression retains a microneedle groove having the shape characteristics of the microneedle model formed by the protrusion. The solidified reverse mold model is the negative mold (12).

4. The method for preparing hollow microneedles according to claim 3, wherein the protrusion length is between 20 and 2000 um.

5. The method for preparing hollow microneedles according to claim 3, wherein the mold material is polydimethylsiloxane or silica gel.

6. The method for preparing hollow microneedles according to claim 5 can be used to prepare hollow microneedles of different shapes by changing the shape of the protrusions on the microneedle model, thereby changing the shape and size of the microneedle grooves in the recess of the female mold (12).

7. The method for preparing hollow microneedles according to claim 1, wherein the liquid material is made of a high molecular polymer.

8. The method for preparing a hollow microneedle according to any one of claims 1 to 7, using a positioning device for the hollow microneedle; The positioning device for the hollow microneedle comprises a base (1), on which a clamping mechanism is arranged, the clamping mechanism comprising two clamps capable of adjusting the spacing; two clamping mechanisms are arranged, and the moving directions of the clamps of the two clamping mechanisms are intersecting; the clamps are used to clamp the outer wall surface of a limiting plate (11) or a female mold (12). 9 . The method for preparing a hollow microneedle according to claim 8 , wherein the two clamping mechanisms have a spacing in the longitudinal direction.

10. According to the method for preparing hollow microneedles according to claim 9, the side lengths of the limiting plate (11) and the female mold (12) are the same, so that the outer walls of the limiting plate (11) and the female mold (12) are located on a virtual tetrahedron.

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