A through-hole microneedle injection head and its preparation method

Abstract

The present invention provides a through-hole microneedle injection head, which relates to the technical field of drug delivery devices. The through-hole microneedle injection head of the present invention sequentially includes a connector, a backing layer, and a plurality of needle bodies from top to bottom; the needle bodies, the backing layer, and the connector are all through-hole structures; the aperture of the through-hole is 1 nm to 5 μm; each needle body has a plurality of micro-outlets. The through-hole microneedle injection head of the present invention has mutually penetrating pores distributed in the needle bodies and the substrate layer, which can be used to store drugs or serve as a flow channel for drugs. The connector can be connected to a syringe to achieve high-dose drug delivery. The through-hole microneedle injection head of the present invention replaces the traditional metal injection needle and can achieve painless subcutaneous injection. Compared with hollow microneedles, the injection head of the present invention is a through-porous structure with a plurality of micro-outlets, which can avoid clogging of drugs during transdermal injection and further improve the drug delivery efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of drug delivery devices, and particularly to a through-hole microneedle injection head and a preparation method thereof. Background Art

[0002] The therapeutic effect of a drug not only depends on the drug itself, but also the drug delivery system has an important impact on the efficacy of the drug. Injection administration provides a fast and direct way to deliver almost any type of drug directly into the body. Its dosage is accurate and the absorption is fast, which can effectively avoid the first-pass effect and improve the therapeutic effect. However, due to the pain, bleeding, tissue damage and potential complications caused by injection needles, people (especially infants and young children) have always had a certain resistance to injection administration; the improper recycling and treatment of a large amount of medical waste brought by disposable syringes, and the transmission of blood-borne pathogens caused by repeated use also pose economic resource and environmental safety hazards to injection administration. Therefore, people have always hoped to develop alternative drug delivery methods to overcome the above-mentioned various defects and deficiencies of current injection administration.

[0003] As an emerging transdermal delivery technology, microneedles can efficiently deliver drugs to the epidermis or the superficial layer of the dermis of the skin without touching the subcutaneous pain nerves by reducing the needle body to a micron-scale size. Therefore, they have the advantages of high efficiency, safety, painlessness and minimally invasive, which can greatly reduce the resistance of patients during traditional injections and improve compliance. However, the size of microneedles and their preparation processes severely limit their drug loading capacity and drug loading uniformity. In addition, hollow microneedles are similar to micro-syringes and can inject drug preparations into the subcutaneous tissue from the hollow structure of the microneedles by using external force, which can solve the problems of drug dosage and dosing accuracy. However, the preparation process required for hollow microneedles is complex, the requirements for the selection of matrix materials are extremely high, and the cost is expensive. Moreover, since each hollow microneedle has only one micro-outlet, it is easily blocked by subcutaneous tissue during transdermal use, which greatly reduces the drug passing rate and limits its application to a great extent. Summary of the Invention

[0004] The purpose of the present invention is to provide a through-hole microneedle injection head and a preparation method thereof. The through-hole microneedle injection head of the present invention can achieve large-dose drug delivery and avoid blockage during transdermal injection.

[0005] In order to achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0006] The present invention provides a through-hole microneedle injection head, which sequentially includes a connector, a backing layer and a plurality of needle bodies from top to bottom; the needle bodies, the backing layer and the connector are all through-hole structures; the aperture of the through-hole is 1 nm to 5 μm; each needle body has a plurality of micro-outlets.

[0007] Preferably, the through holes include micro holes, mesopores and macropores.

[0008] Preferably, the height of the needle body is 0.4 - 1 mm; the diameter of the joint is 0.15 - 3.81 mm, and the height is 0.4 - 1 mm; the thickness of the backing layer is 1.5 - 10 mm.

[0009] Preferably, the surface of the backing layer is covered with a waterproof layer.

[0010] Preferably, in the direction from the needle body to the joint of the through-hole microneedle injector head, the aperture of the through hole gradually increases or gradually decreases.

[0011] The present invention provides a method for preparing the through-hole microneedle injector head described in the above solution, comprising the following steps:

[0012] Dissolve a medical polymer in a good solvent, and mix the obtained solution with a poor solvent of the medical polymer to obtain a metastable polymer solution of a two-phase solvent system; the metastable polymer solution comprises 5 - 25 wt% of the medical polymer, 50 - 70 wt% of the good solvent, and 5 - 45 wt% of the poor solvent;

[0013] Fill the metastable polymer solution into a microneedle injector head mold, cure it, then perform solvent replacement to remove the good solvent, and demold after drying to obtain a through-hole microneedle array with a backing layer;

[0014] Carve a joint on the backing layer of the through-hole microneedle array with a backing layer by a laser engraving machine to obtain the through-hole microneedle injector head.

[0015] Preferably, before filling the metastable polymer solution into the microneedle injector head mold, it further includes: first filling a three-phase solvent system polymer solution into the microneedle injector head mold; the three-phase solvent system polymer solution is obtained by mixing the metastable polymer solution with a third-phase solvent, and the third-phase solvent is 5 - 70 wt% of the metastable polymer solution; the third-phase solvent can dissolve the medical polymer but has a lower dissolution ability for the medical polymer than the good solvent.

[0016] Preferably, the medical polymer is one or more of polylactic acid, poly(lactic acid - glycolic acid) copolymer, polycaprolactone, polyhydroxyalkanoate and cellulose; the good solvent is one or more of dichloromethane, dioxane, dimethyl sulfoxide and N,N - dimethylformamide; the poor solvent is one or more of water, ethanol, acetone and n - hexanol.

[0017] Preferably, after the joint is carved, it further includes inserting the obtained microneedle injection head into a microneedle template filled with a soluble polymer solution, drying and demolding to obtain a through-hole microneedle injection head with the microneedle body covered by the polymer solution; then spraying a waterproof layer so that the microneedle injection head is coated with a waterproof layer except for the needle body and joint parts; after drying, washing off the soluble polymer covering the needle body part to obtain a through-hole microneedle injection head with the waterproof layer covering other parts except the needle body and joint.

[0018] Preferably, the solvent used for solvent replacement includes 0-100 wt% of water and 0-100 wt% of methanol.

[0019] The present invention provides a through-hole microneedle injection head, which sequentially includes a joint, a backing layer, and a plurality of needle bodies from top to bottom; the needle bodies, the backing layer, and the joint are all through-hole structures; the aperture of the through-hole is 1 nm to 5 μm; each needle body has multiple micro-outlets.

[0020] The through-hole microneedle injection head of the present invention has mutually penetrating pores distributed in the needle body and the lining layer, which can be used to store drugs or serve as drug flow channels. The joint can be connected to a syringe to achieve high-dose drug delivery. The through-hole microneedle injection head of the present invention replaces the traditional metal injection needle and can achieve painless subcutaneous injection. Compared with hollow microneedles, the injection head of the present invention is a through-hole porous structure with multiple micro-outlets, which can avoid drug blockage during transdermal injection and further improve the drug delivery efficiency.

[0021] Furthermore, in the through-hole microneedle injection head of the present invention, from the direction of the needle body to the joint, the aperture of the through-hole gradually becomes larger or gradually becomes smaller, having a gradient modulus, and has better mechanical properties compared with ordinary porous microneedles, which can ensure that the microneedle can smoothly penetrate the skin without breaking. Description of the Drawings

[0022] Figure 1 is a schematic structural diagram of the through-hole microneedle injection head of the present invention;

[0023] Figure 2 is a schematic diagram for the preparation of a metastable polymer solution;

[0024] Figure 3 is a flow chart for the preparation of a microneedle injection head template;

[0025] Figure 4 is a schematic diagram for the preparation of a through-hole microneedle injection head;

[0026] Figure 5 is a schematic diagram for the sealing treatment of a through-hole microneedle injection head;

[0027] Figure 6 is a scanning electron microscope image of the through-hole microneedle injection head prepared in Example 3;

[0028] Figure 7 Force-displacement curve of the through-hole microneedle injection head prepared in Example 3;

[0029] Figure 8 Dermoscope of the through-porous microneedle prepared in Example 3 piercing the back skin of a mouse. Detailed implementation manners

[0030] The present invention provides a through-hole microneedle injection head, which sequentially includes a connector, a backing layer, and a plurality of needles from top to bottom; the needles, the backing layer, and the connector are all through-hole structures; the aperture of the through-hole is 1 nm to 5 μm; each needle has a plurality of micro-outlets.

[0031] The structure of the through-hole microneedle injection head of the present invention is as Figure 1 shown. In the present invention, the height of the needle is preferably 0.4 to 1 mm, more preferably 0.6 to 0.8 mm; the bottom diameter of the needle is preferably 0.2 to 1 mm, more preferably 0.3 to 0.5 mm. In the present invention, the plurality of needles are preferably arranged at equal intervals. The present invention has no special requirements on the number and arrangement rules of the needles, and those skilled in the art can set them according to actual needs.

[0032] In the present invention, the diameter of the connector is preferably 0.15 to 3.81 mm, and the height is preferably 0.4 to 1 mm, more preferably 0.5 to 0.7 mm. In the present invention, the function of the connector is to be connected to a syringe, and those skilled in the art can further determine the appropriate size of the connector according to the model of the syringe to be connected.

[0033] In the present invention, the thickness of the backing layer is preferably 1.5 to 10 mm. In the present invention, the surface of the backing layer is preferably covered with a waterproof layer. The present invention has no special requirements on the specific composition and thickness of the waterproof layer, as long as it can achieve a waterproof effect. In the present invention, the function of the waterproof layer is to seal the backing layer to ensure that when in use, the drug flows in from the connector and flows out from the needle, and does not flow out from the backing layer.

[0034] In the present invention, the needles, the backing layer, and the connector are all through-hole structures. In the present invention, the through-hole structure refers to an interconnected pore structure. In the present invention, the aperture of the through-hole is preferably 1 nm to 5 μm. In the present invention, the through-hole preferably includes micropores, mesopores, and macropores.

[0035] The through-hole microneedle injection head of the present invention has pores that penetrate each other in the needle body and the backing layer, which can be used to store drugs or serve as channels for drug circulation. The connector can be connected to a syringe to achieve large-dose drug delivery. The through-hole microneedle injection head of the present invention replaces the traditional metal injection needle and can achieve painless subcutaneous injection. Compared with hollow microneedles, the injection head of the present invention has a through-hole porous structure with multiple micro-outlets, which can avoid blockage of drugs during transdermal injection and further improve the drug delivery efficiency.

[0036] In the present invention, in the direction from the needle body to the connector of the through-hole microneedle injection head, the aperture of the through-hole gradually becomes larger or smaller. The through-hole microneedle injection head of the present invention has a gradient modulus and better mechanical properties compared with ordinary porous microneedles, which can ensure that the microneedle smoothly penetrates the skin without breaking.

[0037] The present invention provides a method for preparing the through-hole microneedle injection head described in the above solution, including the following steps:

[0038] Dissolve a medical polymer in a good solvent, and mix the obtained solution with a poor solvent of the medical polymer to obtain a metastable polymer solution of a two-phase solvent system; the metastable polymer solution includes 5-25 wt% of the medical polymer, 50-70 wt% of the good solvent, and 5-45 wt% of the poor solvent;

[0039] Fill the metastable polymer solution into a microneedle injection head mold, cure it, then perform solvent replacement to remove the good solvent, and demold after drying to obtain a through-hole microneedle array with a backing layer;

[0040] Carve a connector on the backing layer of the through-hole microneedle array with a backing layer through a laser engraving machine to obtain the through-hole microneedle injection head.

[0041] In the present invention, unless otherwise specified, the raw materials used are all well-known commercially available products in the art.

[0042] The present invention dissolves a medical polymer in a good solvent, and mixes the obtained solution with a poor solvent of the medical polymer to obtain a metastable polymer solution of a two-phase solvent system.

[0043] In the present invention, the medical polymer is preferably one or more of polylactic acid, poly(lactic-co-glycolic acid), polycaprolactone, polyhydroxyalkanoates, and cellulose, and more preferably polylactic acid.

[0044] In the present invention, the good solvent is preferably one or more of dichloromethane, dioxane, dimethyl sulfoxide, and N,N-dimethylformamide; when there are multiple ones, the present invention has no special requirements for the ratio of each good solvent, and any ratio can be used.

[0045] In the present invention, the poor solvent is preferably one or more of water, ethanol, acetone, and n-hexanol; when there are multiple poor solvents, the present invention has no special requirements for the ratio of each poor solvent, and any ratio is acceptable.

[0046] In the present invention, the metastable polymer solution comprises 5-25 wt% of a medical polymer, 50-70 wt% of a good solvent, and 5-45 wt% of a poor solvent; further preferably, the medical polymer is 10-20 wt%, the good solvent is 55-65 wt%, and the poor solvent is 10-40 wt%. The present invention can control the size of the through-holes by controlling the concentration of the medical polymer in the metastable polymer solution. In the present invention, as the polymer concentration decreases, the pore diameter of the through-holes gradually increases.

[0047] Figure 2 It is a schematic diagram for preparing the metastable polymer solution.

[0048] After obtaining the metastable polymer solution of the two-phase solvent system, the present invention fills the metastable polymer solution into a microneedle injection head mold, cures it, replaces the good solvent by solvent replacement, dries it, and demolds it to obtain a through-hole microneedle array with a backing layer.

[0049] In the present invention, the material of the microneedle template is preferably polydimethylsiloxane (PDMS). In the present invention, the microneedle injection head mold is preferably prepared by self-preparation. As Figure 3 shown, the preparation method of the microneedle injection head mold preferably includes the following steps: mixing PDMS and a curing agent in a mass ratio of 10:1 and pouring them into a mold to obtain a PDMS plate with a uniform thickness; using laser engraving to process the PDMS plate to form a groove matching the structure of the microneedle syringe to obtain the microneedle injection head mold.

[0050] As Figure 3 shown, in the present invention, the groove of the microneedle injection head mold includes a microneedle cavity and a backing layer groove. The depth a of the microneedle cavity corresponds to the height of the needle body, and the depth b of the backing layer groove ≥ the thickness of the backing layer of the through-hole microneedle injection head + the height of the joint.

[0051] Before filling the metastable polymer solution into the microneedle injection head mold, the present invention preferably further includes: first filling a three-phase solvent system polymer solution into the microneedle injection head mold.

[0052] In the present invention, the polymer solution of the three-phase solvent system is preferably obtained by mixing a metastable polymer solution and a third-phase solvent, and the third-phase solvent is preferably 5-70 wt% of the metastable polymer solution; the third-phase solvent can dissolve the medical polymer but has a lower dissolving ability for the medical polymer than the good solvent. In the present invention, the third-phase solvent is preferably N,N-dimethylformamide or methyl ethyl ketone. In the present invention, the good solvent and the third-phase solvent cannot both be N,N-dimethylformamide.

[0053] In the present invention, the addition of the third-phase solvent can slow down the phase separation rate, which is beneficial to the preparation of microneedles. When preparing the through-hole microneedle injection head only with the metastable polymer solution, the phase separation rate is relatively fast, and it often occurs that the polymer solution has completely phase-separated before the mold is completely filled, resulting in the situation where the microneedles cannot be formed.

[0054] In the present invention, when using the polymer solution of the three-phase solvent system, since it breaks the balance of the two-phase system, the size of the water-in-oil part in the system is changed, resulting in a modulus gradient in the porous structure of the microneedles after drying and demolding, that is, the pore size is variable.

[0055] The present invention has no special requirements for the dosage of the polymer solution of the three-phase solvent system, and those skilled in the art can adjust it according to needs. In the present invention, the volumes of the polymer solution of the three-phase solvent system and the metastable polymer solution of the two-phase solvent system used for subsequent filling are preferably equal.

[0056] After filling the microneedle injection head mold with the polymer solution of the three-phase solvent system, the present invention preferably centrifuges first and then fills the metastable polymer solution.

[0057] In the present invention, the centrifugation time is preferably 5 minutes. The present invention centrifuges to better fill the tip part of the microneedle injection head mold with the polymer solution of the three-phase solvent system.

[0058] In the present invention, the curing is preferably at room temperature; the present invention has no special requirements for the curing time, and it can achieve the curing effect.

[0059] In the present invention, the solvents used for solvent replacement preferably include 0-100 wt% of water and 0-100 wt% of methanol, and more preferably water or methanol.

[0060] In the present invention, the solvent replacement is preferably to put the cured sample together with the microneedle injection head mold into the solvent. The present invention has no special requirements for the dosage of the solvent, and it can immerse the sample. In the present invention, the solvent replacement time is preferably 24 hours.

[0061] The present invention utilizes solvent replacement to remove the good solvent and form a through-porous structure.

[0062] The present invention has no special requirements for the drying and demolding processes, and the well-known drying and demolding processes in the art can be adopted.

[0063] After obtaining the through-hole microneedle array with a backing layer, the present invention engraves a joint on the backing layer of the through-hole microneedle array with a backing layer by a laser engraving machine to obtain the through-hole microneedle injector. The present invention has no special requirements for the laser engraving process, and a joint with corresponding dimensions can be engraved.

[0064] After engraving the joint, as Figure 5 shown, the present invention preferably further includes inserting the obtained microneedle injector into a microneedle template filled with a soluble polymer solution, drying and demolding to obtain a through-hole microneedle injector with the microneedle body covered by the polymer solution; then spraying a waterproof layer so that a waterproof layer is coated on the microneedle injector except for the needle body and the joint part; after drying, washing away the soluble polymer covering the needle body part to obtain a through-hole microneedle injector with a waterproof layer covering other parts except the needle body and the joint. In the present invention, the soluble polymer is preferably polyvinyl alcohol.

[0065] The following will specifically describe the through-hole microneedle injector and its preparation method provided by the present invention in conjunction with embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0066] Example 1

[0067] This example provides a through-hole microneedle injector with a biodegradable medical polymer polylactic acid as the matrix material, and the specific preparation steps are as follows:

[0068] (1) As Figure 2 shown, prepare a polylactic acid metastable solution: Weigh 1.0 g of polylactic acid particles and place them in a reaction flask, add 8 mL of dichloromethane to dissolve them fully, and then add 2 mL of ultrapure water and stir well to obtain a polylactic acid metastable solution;

[0069] (2) As Figure 3 shown, prepare a microneedle injector mold: First, fully mix polydimethylsiloxane (PDMS) and a curing agent in a mass ratio of 10:1 and pour them into a mold to obtain a PDMS plate with a uniform thickness; then adjust the mode and power of the laser engraving machine to prepare a microneedle injector template;

[0070] (3) As Figure 4As shown in the figure, the micro-needle injection head is prepared by the template filling method: Pour the metastable solution of polylactic acid onto the micro-needle injection head template, cure it at room temperature, then soak it in an aqueous solution for solution replacement to cause phase separation and remove dichloromethane, and obtain through-hole micro-needles after drying; Use a laser engraving machine to cut the back lining layer of the micro-needles to engrave the joint, and obtain a through-hole micro-needle injection head that can be connected to syringes of different specifications. The height of the needle body is 0.8 mm, the bottom diameter is 0.5 mm, the thickness of the back lining layer is 2 mm, the height of the joint is 0.7 mm, and the diameter of the joint is 1 mm.

[0071] Example 2

[0072] Seal the parts of the through-hole micro-needle injection head in Example 1 other than the needle body and the joint to ensure that the liquid medicine enters from the joint and flows out from the needle body into the subcutaneous tissue during injection, thereby improving the drug delivery efficiency. The specific operation steps are as follows:

[0073] As Figure 5 shown, first fill the micro-needle template with a soluble polymer solution (a 40% mass concentration polyvinyl alcohol solution), align and insert the through-hole micro-needle injection head into the template filled with the soluble polymer solution, and obtain a through-hole micro-needle injection head with the micro-needle body covered with the polymer solution after drying and demolding; Then spray a waterproof layer to coat a dense waterproof layer on the micro-needle injection head except for the needle body and the joint parts; After drying, wash off the soluble polymer covering the needle body part, and finally obtain a through-hole micro-needle injection head with the parts other than the needle body and the joint sealed.

[0074] Example 3

[0075] This example provides a through-hole micro-needle injection head with a modulus gradient based on the biodegradable medical polymer polylactic acid as the matrix material. The specific preparation steps are as follows:

[0076] (1) Prepare a three-phase system polylactic acid metastable solution: Weigh 1.0 g of polylactic acid particles and place them in a reaction flask, add 8 mL of dichloromethane to dissolve them fully, then add 1 mL of ultrapure water and 1 mL of N-methylpyrrolidone and stir well to obtain a three-phase system polylactic acid metastable solution;

[0077] (2) As Figure 2 shown, prepare a two-phase system polylactic acid metastable solution: Weigh 1.0 g of polylactic acid particles and place them in a reaction flask, add 8 mL of dichloromethane to dissolve them fully, then add 2 mL of ultrapure water and stir well to obtain a two-phase system polylactic acid metastable solution;

[0078] (3) As Figure 3As shown in the figure, prepare the microneedle injection head template: First, fully mix polydimethylsiloxane (PDMS) and a curing agent in a mass ratio of 10:1, and then pour the mixture into a mold to obtain a PDMS plate with a uniform thickness; then, adjust the mode and power of a laser engraving machine to prepare the microneedle injection head template;

[0079] (4) As Figure 4 shown in the figure, prepare the microneedle injection head by the template filling method: Pour the metastable solution of poly(lactic acid) in three phases onto the microneedle injection head template, and after centrifuging for 5 minutes, let the solution fill the mold cavity. Remove the excess metastable solution of poly(lactic acid) in three phases, pour the metastable solution of poly(lactic acid) in two phases onto the template, so that the volume of the metastable solution of poly(lactic acid) in three phases in the template is equal to the volume of the metastable solution of poly(lactic acid) in two phases. After curing at room temperature, soak it in an aqueous solution for solvent replacement to remove the organic solvent, and after drying, obtain a through-hole microneedle with a modulus gradient; use a laser engraving machine to cut the microneedle backing layer to obtain a through-hole microneedle injection head with a modulus gradient that can be connected to a syringe, with a needle body height of 1 mm, a bottom diameter of 0.5 mm, a backing layer thickness of 3 mm, a joint height of 0.6 mm, and a joint diameter of 1.2 mm.

[0080] Structure characterization:

[0081] Perform scanning electron microscopy observation on the through-hole microneedle injection head prepared in Example 3, and the results are as Figure 6 shown in the figure. It can be seen from Figure 6 the figure that the through-hole microneedles prepared by the present invention simultaneously have macropores, mesopores, and micropores; and exhibit a modulus gradient, that is, the pore size changes from the needle body to the joint direction are micropores, mesopores, and macropores in turn, with micropores at the tip of the needle, mesopores in the needle body part, and macropores in the joint part.

[0082] Figure 7 is the force-displacement curve of the through-hole microporous microneedles prepared in Example 3. It can be seen from Figure 7 the figure that a single porous microneedle can withstand a force of 0.1 N without breaking, indicating that the porous microneedles have sufficient mechanical strength to penetrate the skin without breaking.

[0083] Figure 8 is the dermoscope of the through-hole porous microneedles prepared in Example 3 penetrating the skin of a mouse's back. It can be seen that the microneedles can completely penetrate the skin, and the penetration depth can reach 0.6 mm.

[0084] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A preparation method of a through-hole microneedle injection head, characterized in that, the specific preparation steps are as follows: (1) Prepare a three-phase system poly(lactic acid) metastable solution: Weigh 1.0 g of poly(lactic acid) particles and place them in a reaction flask. Add 8 mL of dichloromethane to dissolve them, then add 1 mL of ultrapure water and 1 mL of N-methylpyrrolidone and stir to obtain a three-phase system poly(lactic acid) metastable solution; (2) Prepare a two-phase system poly(lactic acid) metastable solution: Weigh 1.0 g of poly(lactic acid) particles and place them in a reaction flask. Add 8 mL of dichloromethane to dissolve them, then add 2 mL of ultrapure water and stir to obtain a two-phase system poly(lactic acid) metastable solution; (3) Prepare a microneedle injection head template: First, fully mix polydimethylsiloxane and a curing agent in a mass ratio of 10:1 and pour them into a mold to obtain a polydimethylsiloxane plate with a uniform thickness; Then, adjust the mode and power of a laser engraving machine to prepare a microneedle injection head template; (4) Prepare a microneedle injection head by the template filling method: Pour the three-phase poly(lactic acid) metastable solution onto the microneedle injection head template, centrifuge for 5 min to allow the solution to fill the mold cavity; Remove the excess three-phase poly(lactic acid) metastable solution, pour the two-phase system poly(lactic acid) metastable solution onto the template so that the volume of the three-phase poly(lactic acid) metastable solution in the template is equal to the volume of the two-phase system poly(lactic acid) metastable solution; After curing at room temperature, soak it in an aqueous solution for solvent replacement to remove organic solvents, and dry it to obtain a through-hole microneedle with a modulus gradient; Use a laser engraving machine to cut the microneedle backing layer to obtain a through-hole microneedle injection head with a modulus gradient that can be connected to a syringe.

2. A through-hole microneedle injection head prepared by the preparation method described in claim 1.

3. The through-hole microneedle injection head according to claim 2, characterized in that, the height of the needle body is 1 mm, the bottom diameter is 0.5 mm, the thickness of the backing layer is 3 mm, the height of the joint is 0.6 mm, and the diameter of the joint is 1.2 mm.

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