A preparation method of hollow microneedle and its mold

Abstract

The present invention relates to the field of hollow microneedle technology, and more specifically to a method for preparing hollow microneedles and a mold thereof. A positioning device is used to clamp a female mold and a limiting plate and fine-tune the relative position of the two, 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 the various processes and materials are inexpensive and easy to obtain, which greatly reduces the manufacturing cost of hollow microneedles; 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; by changing the size and shape of the guide wire, hollow microneedles with different holes can be prepared; by adding different microneedle preparation solutions, the platform can be applied to the production of hollow microneedles of different materials; in summary, the hollow microneedle preparation method has the characteristics of low cost, versatility, and high personalization.

Description

Technical Field

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

[0002] Microneedles can easily penetrate the stratum corneum of the skin to form drug channels, allowing drug delivery without gastrointestinal metabolism or the first-pass effect in the liver. Microneedles are classified into various categories, including solid microneedles, hollow microneedles, and dissolving microneedles. Hollow microneedles, which have hollow channels, are more capable of delivering large doses of drugs than other types of microneedles, making them promising for broad medical applications. However, hollow microneedles are difficult to prepare. Existing methods include photolithography, 3D printing, drip injection, and centrifugation. Photolithography is expensive, complex, and has significant material limitations. 3D printing also limits the materials that can be used for hollow microneedle preparation and has relatively high equipment costs. The drip injection method cannot produce microneedles with controllable morphology, as the outer boundary of the microneedle is determined by the tension of the liquid material before solidification and cannot be manually designed. Hollow microneedles prepared by centrifugation have larger internal pores and a microneedle shape similar to that of a shell, resulting in poor mechanical properties, which greatly limits their further application. Therefore, the research and development of preparation methods and related molds for hollow microneedles that are low-cost, have controllable shapes and internal pores, and are compatible with multiple materials are of great significance. 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 objectives are achieved through the following technical solutions:

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

[0006] Step 1: forming a hole on the limiting plate, forming a depression and a microneedle groove 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 carried out 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 preparation method of the female mold comprises the following steps:

[0010] Step 1: Prepare a microneedle model, including a base and a protrusion fixed to the upper end of the base, and immerse the microneedle model in a molding material;

[0011] Step 2: After the mold material is solidified, the microneedle model is removed 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. The solidified mold model is the negative mold.

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

[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 hollow microneedles;

[0018] The positioning device of the hollow microneedle includes a base, on which a clamping mechanism is provided, and the clamping mechanism includes two clamps capable of adjusting the spacing; there are two clamping mechanisms, and the clamp movement directions of the two clamping mechanisms are cross-sectional; the clamp is used to clamp the limit plate or the outer wall surface of 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 outer walls of the limiting plate and the female mold are located on a virtual tetrahedron.

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

[0022] The female mold and the limiting plate are clamped by a positioning device and their relative positions are finely adjusted. A guide wire is then passed through to obtain a hollow microneedle manufacturing mold. This mold can be used to cast hollow microneedles in one step. This mold can be reused multiple times. Each process and material is inexpensive and easily available, greatly reducing 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, this platform can be applied to the production of hollow microneedles made of different materials; in summary, this hollow microneedle preparation method is low-cost, universal, and highly personalized. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0027] Figure 2 Schematic diagram of a preparation mold for fixing hollow microneedles to a positioning device for hollow microneedles;

[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 A schematic diagram of the structure of the first slider and the second slider;

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

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

[0033] Figure 8 Schematic diagram of the structure of the first clamping joint and the second clamping joint;

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

[0035] Figure 10 Schematic diagram of the structure of the limiting plate;

[0036] Figure 11 Schematic diagram of the structure of the female mold;

[0037] Figure 12 Schematic diagram of the guide wire structure;

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

[0039] Figure 14 Schematic diagram of the guidewire 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 μm.

[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 removed 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. Figure 11 The upper end of the female mold 12 has a depression, and a microneedle groove is formed in the depression.

[0046] Among them, by changing the shape of the protrusions on the microneedle model, the shape and size of the microneedle grooves in the depression of the female mold 12 are changed, which 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 set on the limiting plate 11, and a female mold 12 is set above the limiting plate 11. The hole on the limiting plate 11 and the microneedle groove on the female mold 12 can partially or completely overlap. Figure 10 In the figure, the inner diameter of the hole of the limiting plate 11 increases from top to bottom. Figure 14, when 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 out 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 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, Figure 14 After the schematic structure in FIG. 1 is turned over, the guide wire 13 is punctured from top to bottom.

[0048] The preparation method of 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 is 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, and 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 and second through holes 107 and 108 are provided on the two first convex walls, one in front and one in the back, respectively. 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 back and forth relative to the base 1. The left and right ends of the rear portion 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 provided on the two second convex walls, one on the left and one on the right, respectively. 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 the convenience of explanation, refer to Figure 4 Taking the first slider 2a as an example, the first slider 2a includes 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 provided on the surface of the vertical body 202 facing the base 1, and a through hole 204 is provided on the vertical body 202 to communicate with the slide rail 203.

[0055] The third clamp 3c and the fourth clamp 3d are slidably connected within the slide rail 203 on the first slider 2a; the first clamp 3a and the second clamp 3b are slidably connected within 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. The first clamp clamping knob 6a is fixedly connected to the first clamp clamping knob 6a. The two ends of the first clamping joint 5a are respectively hinged to one end of the third rotation joint 4c and one end of the fourth rotation joint 4d. The other ends of the third rotation joint 4c and the other ends of the fourth rotation 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 pass 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 rotation joint 4a and one end of the second rotation joint 4b. The other end of the third rotation joint 4c and the other end of the fourth rotation joint 4d are respectively hinged to the fourth clamp 3d and the third clamp 3c.

[0057] Rotating the first clamp's clamping knob 6a adjusts the distance between the fourth clamp 3d and the third clamp 3c, while rotating the second clamp's clamping knob 6b adjusts the distance between the first clamp 3a and the second clamp 3b. The first and second clamp's clamping knobs 6a and 6b have identical structures, each consisting of a bolt-nut assembly. The nut is screwed onto the bolt, and rotating the nut presses against the base 1, preventing the bolt connected to the base 1 from rotating. Alternatively, utilizing the principle of damping, the first and second clamp's clamping knobs 6a and 6b can be connected to the base 1 in a damped rotational manner.

[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 rests on the first slider 2a. The first limiting bolt 8a is connected to the first nut 9a through threaded fitting. The first nut 9a rests on the right end of the inner wall of the base 1, and the first limiting bolt 8a rests on 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, with the first slider 2a being 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 fixed with a first side support 7a, a second side support 7b, a third side support 7c and a fourth side support 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] The solution for making the microneedles may also be various solutions such as polylactic acid-co-glycolic acid copolymer, hyaluronic acid, light-cured gelatin, chitosan, or other solutions capable of preparing microneedle solutions. The specific shape and structure of the hollow microneedle patch may also be various shapes. This is not intended to limit the invention in other forms. Any person skilled in the art may use the above-disclosed technical content to make changes or modifications to equivalent embodiments with equivalent changes. However, any simple modification, equivalent change, and modification of the above embodiments made in accordance with the technical essence of the present invention without departing from the technical solution of the present invention shall still fall within the scope of protection of the present invention.

Claims

1. A method for preparing a hollow microneedle, comprising the following steps: Step 1: forming a hole on the limiting plate (11), forming a depression and a microneedle groove on the female mold (12), and the microneedle groove is located in the depression; Step 2: Use the 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), and after puncture, the guide wire (13) is located in the microneedle groove on the female mold (12), and the liquid material for preparing the hollow microneedle is injected into the female mold (12). After solidification, the material is demoulded to obtain the hollow microneedle; The inner diameter of the hole of the limiting plate (11) gradually decreases at one end close to the female mold (12); A positioning device using hollow microneedles; The positioning device of the hollow microneedle comprises a base (1), the base (1) is provided with a clamping mechanism, the clamping mechanism comprises two clamps capable of adjusting the spacing; two clamping mechanisms are provided, and the clamps of the two clamping mechanisms move in intersecting directions; the clamps are used to clamp the outer wall surface of the limiting plate (11) or the female mold (12); The two clamping mechanisms are spaced apart in the longitudinal direction.

2. The method for preparing the hollow microneedle according to claim 1, wherein the method for preparing the female mold (12) comprises the following steps: Step 1: Prepare a microneedle model, including a base and a protrusion fixed to the upper end of the base, and immerse the microneedle model in a molding material; Step 2: After the mold material is solidified, the microneedle model is removed from the solidified mold material; Step 3: The solidified 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 mold model is the negative mold (12).

3. The method for preparing hollow microneedles according to claim 2, wherein the protrusion length is between 20 and 2000 μm.

4. The method for preparing hollow microneedles according to claim 2, wherein the mold material is polydimethylsiloxane or silica gel.

5. The method for preparing hollow microneedles according to claim 4 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).

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

7. The method for preparing hollow microneedles according to claim 1, wherein 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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