Microneedle female die, microneedle and preparation method of microneedle female die

Abstract

The invention discloses a microneedle female die, a microneedle and a preparation method of the microneedle female die, and relates to the technical field of microneedle machining, the microneedle female die is made of a die material and is provided with a cavity matched with the structure of a target microneedle, and after the target microneedle is formed in the cavity, the die material of the microneedle female die is separated from the target microneedle in a heating and / or dissolving mode. The problem that the quality of the microneedle is affected by a conventional separation mode of the microneedle and the microneedle female die is solved.

Description

Technical Field

[0001] This application relates to the field of microneedle fabrication technology, and in particular to microneedle negative molds, microneedles, and their preparation methods. Background Technology

[0002] With the development of transdermal drug delivery and the popularity of the medical aesthetics industry, microneedles, a new form of delivery system, create micron-sized channels in the skin surface, allowing drug molecules and active ingredients to penetrate the stratum corneum barrier and enter the microcirculation.

[0003] In current microneedle fabrication processes, PDMS (polydimethylsiloxane) and metal molds are commonly used. Due to the fine structure of the microneedle body and tip, conventional molds themselves need to have high precision to meet the requirements of accurate microneedle fabrication, which also leads to the problem of high microneedle mold manufacturing costs. At the same time, during the separation process of microneedles from molds, due to the interaction force between the mold and microneedle materials, conventional peeling or sticking methods often lead to microneedle tip breakage and needle body deformation, which in turn affects the use of microneedles and the accuracy of molds. Therefore, conventional molds and separation methods seriously hinder the industrialization of large-area non-destructive microneedles.

[0004] The above content is only used to help understand the technical solution of this application and does not represent an admission that the above content is prior art. Summary of the Invention

[0005] The main purpose of this application is to provide a microneedle negative mold, microneedles and their preparation method, which aims to solve the problem that the separation method of conventional microneedles and microneedle negative mold affects the quality of microneedles.

[0006] To achieve the above objectives, this application proposes a microneedle negative mold, which is made of mold material and has a cavity that matches the structure of the target microneedle. After the target microneedle is formed in the cavity, the mold material of the microneedle negative mold is separated from the target microneedle by heating and / or dissolving.

[0007] In one feasible embodiment, the mold material includes at least one of paraffin wax, beeswax, microcrystalline wax, polyethylene wax, palm wax, ice, stearyl alcohol, low molecular weight polycaprolactone, glyceryl behenate, and lactic acid-glycolic acid copolymer.

[0008] This application provides a method for preparing microneedles, using the microneedle negative mold as described above, the method comprising: Microneedle positive molds are available; The molten mold material is combined with the microneedle male mold; After lamination, the microneedle mold is cooled and shaped, and then separated to obtain the microneedle negative mold, wherein a cavity matching the structure of the target microneedle is formed in the microneedle negative mold; The microneedle formulation is filled into the cavity and solidified. The microneedle negative mold is removed by heating and / or dissolving to obtain the target microneedle.

[0009] In one feasible embodiment, the heating method includes at least one of infrared heating, ultrasonic heating, microwave heating and electric heating; And / or, the solvent for dissolution includes at least one of petroleum ether, n-hexane, cyclohexane, toluene, xylene, and chloroform.

[0010] In one feasible embodiment, the heating temperature is 40°C to 150°C.

[0011] In one feasible embodiment, the recombination time is 20s to 3600s; And / or, the temperature of the composite is 40℃~150℃; And / or, the cooling temperature is -20℃ to 30℃.

[0012] In one feasible embodiment, the microneedle material in the microneedle male mold includes at least one of polycarbonate, polymethyl methacrylate, polydimethylsiloxane, stainless steel, aluminum alloy, copper, and chromium steel; And / or, the microneedle formulation comprises at least one of sodium hyaluronate, chitosan, carrageenan, pectin, konjac polysaccharide, polydimethylsiloxane, polylactic acid, and polycaprolactone.

[0013] In one feasible embodiment, the structure of the target microneedle includes a solid structure and / or a hollow structure.

[0014] In one feasible embodiment, after the step of removing the microneedle negative mold to obtain the target microneedle, the method further includes: The removed microneedle negative mold is collected, remelted, and combined with the microneedle positive mold, then cooled and shaped to prepare a new microneedle negative mold.

[0015] This application also provides a microneedle prepared by the microneedle preparation method described above.

[0016] One or more technical solutions proposed in this application have at least the following technical effects: A microneedle negative mold, made of mold material, has a cavity matching the structure of the target microneedle. After the target microneedle is formed in the cavity, the mold material of the microneedle negative mold is separated from the target microneedle by heating and / or dissolving. Conventional methods of separating the target microneedle from the microneedle negative mold often employ mechanical demolding, such as direct pulling or squeezing, which can easily cause physical damage to the target microneedle, leading to problems such as breakage and deformation, thereby affecting the quality and performance of the microneedle. However, the embodiments of this application use heating and / or dissolving to separate the microneedle negative mold, avoiding direct mechanical force, reducing the mechanical force borne by the microneedle, better maintaining the integrity and shape accuracy of the target microneedle, and ensuring stable microneedle quality. The embodiments of this application solve the problem that conventional methods of separating the microneedle from the microneedle negative mold affect the quality of the microneedle. Attached Figure Description

[0017] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this application and, together with the description, serve to explain the principles of this application.

[0018] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, for those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 A schematic flowchart illustrating the microneedle preparation method provided in this application embodiment; Figure 2 A schematic diagram illustrating the process of fabricating solid microneedles according to embodiments of this application; Figure 3 This is a schematic diagram of the process for preparing hollow microneedles according to an embodiment of this application.

[0020] Explanation of icon numbers: 10. Microneedle male mold; 20. Mold material; 30. Microneedle female mold; 40. Microneedle formulation; 50. Target microneedle.

[0021] The purpose, features, and advantages of this application will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0023] The following detailed description, with appropriate reference to the accompanying drawings, discloses embodiments of the microneedle negative mold, microneedles, and methods for preparing the same thereof. However, unnecessary details may be omitted. For example, detailed descriptions of well-known matters and repetitive descriptions of practically identical structures may be omitted. This is to avoid unnecessarily lengthy descriptions and to facilitate understanding by those skilled in the art. Furthermore, the accompanying drawings and the following description are provided for the purpose of enabling those skilled in the art to fully understand this application and are not intended to limit the subject matter of the claims.

[0024] The "range" disclosed in this application is defined by a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, which define the boundaries of a particular range. Ranges defined in this way can include or exclude endpoints and can be arbitrarily combined; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60~120 and 80~110 are listed for a specific parameter, it is also expected that ranges of 60~110 and 80~120 are also included. Furthermore, if minimum range values ​​of 1 and 2 are listed, and if maximum range values ​​of 3, 4, and 5 are listed, then the following ranges are all expected: 1~3, 1~4, 1~5, 2~3, 2~4, and 2~5. In this application, unless otherwise stated, the numerical range "a~b" represents a shortened representation of any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0~5" indicates that all real numbers between "0~5" have been listed in this article; "0~5" is simply a shortened representation of these numerical combinations. Furthermore, when a parameter is stated as an integer ≥2, it is equivalent to disclosing that the parameter is, for example, an integer such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0025] Unless otherwise specified, all embodiments and optional embodiments of this application can be combined to form new technical solutions.

[0026] Unless otherwise specified, all technical features and optional technical features of this application may be combined to form new technical solutions.

[0027] Unless otherwise specified, all steps in this application may be performed sequentially or randomly, preferably sequentially. For example, the method includes steps (a) and (b), indicating that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the mention that the method may also include step (c) indicates that step (c) may be added to the method in any order. For example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc.

[0028] Unless otherwise specified, the terms "comprising" and "including" as used in this application can be open-ended or closed-ended. For example, "comprising" and "including" can mean that other components not listed may also be included, or that only the listed components may be included.

[0029] Unless otherwise specified, the term "or" is inclusive in this application. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, the condition "A or B" is satisfied by any of the following conditions: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0030] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, the technical solution of this application is further described below in conjunction with the accompanying drawings and embodiments. However, this application is not limited to the listed embodiments, but should also include any other well-known modifications within the scope of the claims made in this application.

[0031] The term "an embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of this application. The phrase "in one embodiment" appearing in different places throughout this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0032] To better understand the technical solution of this application, a detailed description will be provided below in conjunction with the accompanying drawings and specific implementation methods.

[0033] In current microneedle fabrication processes, PDMS (polydimethylsiloxane) and metal molds are commonly used. Due to the fine structure of the microneedle body and tip, conventional molds themselves need to have high precision to meet the requirements of accurate microneedle fabrication, which also leads to the problem of high microneedle mold manufacturing costs. At the same time, during the separation process of microneedles from molds, due to the interaction force between the mold and microneedle materials, conventional peeling or sticking methods often lead to microneedle tip breakage and needle body deformation, which in turn affects the use of microneedles and the accuracy of molds. Therefore, conventional molds and separation methods seriously hinder the industrialization of large-area non-destructive microneedles.

[0034] This application provides a microneedle negative mold. The microneedle negative mold is made of a mold material and has a cavity that matches the structure of the target microneedle. After the target microneedle is formed within the cavity, the mold material of the microneedle negative mold is separated from the microneedle by heating and / or dissolving. Conventional methods for separating the target microneedle from the microneedle negative mold often employ mechanical demolding, such as direct pulling or squeezing. These methods can easily cause physical damage to the microneedle, leading to problems such as breakage and deformation, thus affecting the quality and performance of the microneedle. This application, however, uses heating and / or dissolving to separate the microneedle negative mold, avoiding direct mechanical force, reducing the mechanical stress on the microneedle, better maintaining the integrity and shape accuracy of the microneedle, and ensuring stable microneedle quality. This application solves the problem of conventional microneedle-microneedle negative mold separation methods affecting microneedle quality.

[0035] Based on this, the first aspect of the present application provides a microneedle negative mold, which is made of mold material and has a cavity that matches the structure of the target microneedle. After the target microneedle is formed in the cavity, the mold material of the microneedle negative mold is separated from the microneedle by heating and / or dissolving.

[0036] In one feasible embodiment, the target microneedle is the final microneedle product to be manufactured, having a specific shape, size, and structure. The cavity shape and size of the microneedle mold match the target microneedle. During the microneedle manufacturing process, the material for preparing the microneedle is filled into the cavity, and after certain processing (such as curing, molding, etc.), the material for preparing the microneedle will form a microneedle with the same structure as the target microneedle within the cavity. After the target microneedle is formed within the cavity of the microneedle mold, the microneedle mold needs to be separated from the microneedle to obtain an independent microneedle product. This is done by heating the microneedle mold to soften or melt the mold material. If the mold material softens or melts after heating, the microneedle can be removed from the mold. A specific solvent is used to dissolve the microneedle mold. The selected solvent needs to be able to selectively dissolve the mold material without damaging the microneedle.

[0037] Alternatively, in some cases, it may be necessary to use both heating and dissolution methods to separate the microneedle mold from the microneedles. For example, the mold can be softened by heating first, and then further dissolved with a solvent, which can improve the efficiency and effectiveness of the separation.

[0038] In one feasible embodiment, the mold material includes at least one of paraffin wax, beeswax, microcrystalline wax, polyethylene wax, carnauba wax, ice, stearyl alcohol, low molecular weight polycaprolactone, glyceryl behenate, and lactic acid-glycolic acid copolymer.

[0039] Optionally, materials such as paraffin wax, beeswax, microcrystalline wax, polyethylene wax, and carnauba wax have relatively low melting points. Upon heating, their fluidity increases, facilitating the filling of cavities in the microneedle mold. They also maintain structural stability upon cooling and possess hydrophobic properties, preventing adhesion to the target microneedle material and reducing demolding resistance. Furthermore, these waxes can be reused through multiple melting cycles, reducing costs.

[0040] Optionally, the mold material can also be a low-melting-point, easily fusible or easily soluble material, such as stearyl alcohol, low molecular weight polycaprolactone, glyceryl behenate, lactic acid-glycolic acid copolymer, etc. These materials have low melting points and can be softened or melted for demolding by heating. They also possess flexibility and support, preventing breakage that easily occurs during microneedle demolding. Furthermore, they have a certain degree of lubrication, which makes it easier for microneedle formulations to fill into the microneedle mold.

[0041] Alternatively, when the mold material is ice, a cryogenic microneedle structure can be used, and separation can be achieved by melting at room temperature during demolding. In addition, this process does not require chemical solvents, which can meet environmental protection requirements and reduce costs.

[0042] The microneedle mold provided in this embodiment is made of mold material and has a cavity that matches the structure of the target microneedle. After the target microneedle is formed in the cavity, the microneedle mold is separated from the microneedle by heating and / or dissolving. Conventional methods for separating the target microneedle from the microneedle mold often use mechanical demolding, such as direct pulling or squeezing. These methods can easily cause physical damage to the microneedle, leading to problems such as breakage and deformation, thereby affecting the quality and performance of the microneedle. However, the embodiment of this application uses heating and / or dissolving to separate the microneedle mold, avoiding direct mechanical force, reducing the mechanical force borne by the microneedle, better maintaining the integrity and shape accuracy of the microneedle, and ensuring stable microneedle quality. This embodiment solves the problem of conventional methods of separating microneedles from microneedles affecting microneedle quality.

[0043] The second aspect of this application provides a method for preparing microneedles, referring to... Figure 1 The methods include: Step S10: Provide a microneedle male mold; In one feasible embodiment, the microneedle male mold provides a precise shape reference for the subsequent fabrication of the microneedle female mold. The protrusions of the male mold form corresponding depressions in the mold material of the microneedle female mold, thereby replicating the shape of the target microneedle.

[0044] Alternatively, a microneedle male mold refers to a mold with a raised structure that is consistent with the structure of the target microneedle.

[0045] Alternatively, microneedle male molds are typically manufactured using micro-nano processing technologies such as photolithography, etching, and micromachining to ensure they have high-precision microstructures.

[0046] In one feasible implementation, the microneedle material in the microneedle male mold includes at least one of polycarbonate, polymethyl methacrylate, polydimethylsiloxane, stainless steel, aluminum alloy, copper, and chromium steel.

[0047] Stainless steel, aluminum alloys, copper, and chromium steel are used to fabricate microneedles in male microneedles because they are easy to mold, can be precisely machined to achieve accurate dimensions and smooth surfaces, facilitating the replication of female microneedles, and possess suitable hardness and sufficient strength to ensure the stability of the microneedles' shape during fabrication and prevent deformation or damage. They also exhibit good chemical stability, are resistant to certain corrosion, and are chemically inert in contact with the female mold material, without reacting. Furthermore, these materials demonstrate stable properties and good batch-to-batch consistency, ensuring uniform microneedle performance and dimensions during mass production, thus guaranteeing the quality of the female microneedles and the final product.

[0048] Polycarbonate, polymethyl methacrylate, and polydimethylsiloxane are polymeric materials with good rigidity and high strength, as well as a certain degree of flexibility and chemical stability. When used as positive molds for preparing negative molds and target microneedles, they can adapt to the operating process and avoid the influence of various chemical substances. Furthermore, they can also prevent the prepared target microneedles from affecting biological tissues.

[0049] Step S20: The molten mold material is combined with the microneedle male mold; In one feasible embodiment, molten mold material is cast or imprinted onto a microneedle male mold, so that the material is in close contact with the male mold, ensuring that the microstructure of the male mold can be completely transferred into the mold material.

[0050] Optionally, the mold material is heated to a molten state, exhibiting good fluidity, and is able to accurately replicate the shape of the microneedle male mold.

[0051] In one feasible implementation, the recombination time is 20s to 3600s.

[0052] The compounding time refers to the duration required for the molten mold material to come into contact with the microneedle male mold and fully fill the microstructure of the male mold. A suitable compounding time ensures that the mold material can completely and accurately replicate the shape of the microneedle male mold.

[0053] Optionally, the compounding time can be 20s, 50s, 100s, 150s, 200s, 250s, 300s, 350s, 400s, 450s, 500s, 650s, 700s, 750s, 800s, 850s, 900s, 1000s, 1200s, 1400s, 1600s, 1800s, 2000s, 2200s, 2400s, 2600s, 2800s, 3000s, 3200s, 3400s, 3600s, etc.

[0054] If the lamination time is too short, the molten mold material may not have enough time to flow fully and contact the microneedle male mold, resulting in an incomplete cavity structure of the microneedle female mold. This, in turn, affects the molding quality of the target microneedles, potentially leading to problems such as incomplete microneedle shapes and inaccurate dimensions. If the lamination time is too long, on the one hand, it will reduce production efficiency and increase production costs. On the other hand, prolonged exposure to a high-temperature molten state may cause thermal degradation, oxidation, and other chemical reactions in the mold material, leading to a decline in material properties and affecting the quality and service life of the microneedle female mold. Furthermore, excessively long contact time may also cause unnecessary adhesion between the mold materials of the microneedle male and female molds, increasing the difficulty of subsequent separation.

[0055] In one feasible implementation, the composite temperature is 40°C to 150°C.

[0056] The composite temperature has a significant impact on the flowability and molding performance of molten mold materials. Selecting an appropriate temperature range can ensure that the mold material has good processability when combined with the microneedle male mold, thereby obtaining a high-quality microneedle female mold.

[0057] Optionally, the temperature for compounding can be 40℃, 50℃, 60℃, 70℃, 80℃, 90℃, 100℃, 110℃, 120℃, 130℃, 140℃, 150℃, etc.

[0058] When the composite temperature is too low, the fluidity of the mold material deteriorates. This is because at lower temperatures, the thermal motion of the mold material molecules slows down, increasing viscosity and making it difficult to fully fill the microstructure of the male mold. This results in inaccurate replication of the microstructure in the microneedle female mold, leading to deviations in the shape and size of the microneedles. Conversely, if the composite temperature is too high, it may damage both the mold material and the microneedle male mold. For the mold material, high temperatures may trigger thermal decomposition and cross-linking reactions, altering its physical and chemical properties and affecting the quality and performance of the female mold. For the microneedle male mold, high temperatures may cause material deformation and expansion, compromising the microstructural precision of the male mold and consequently affecting the subsequent fabrication of microneedles.

[0059] Step S30: After the composite is completed, the mold is cooled and formed, and then separated to obtain a microneedle negative mold, wherein a cavity matching the structure of the target microneedle is formed in the microneedle negative mold; After the mold material is bonded to the microneedle male mold, the molten mold material is solidified through natural or forced cooling. During the cooling process, the molecular structure of the material gradually stabilizes, forming a microneedle female mold with a certain strength and stability. Once the mold material has completely cooled and solidified, the microneedle female mold is carefully separated from the microneedle male mold. Separation methods typically include mechanical and chemical demolding. The resulting microneedle female mold has a cavity structure with the same shape as the target microneedles.

[0060] In one feasible implementation, the cooling and molding temperature is -20°C to 30°C.

[0061] In one feasible embodiment, cooling molding refers to the solidification of molten microneedle mold material to form a structure with certain strength and stability.

[0062] Optionally, the cooling and molding temperature can be -20℃, -15℃, -10℃, -5℃, 0℃, 5℃, 10℃, 15℃, 20℃, 25℃, 30℃, etc.

[0063] Alternatively, if the temperature is too low, the mold material may generate internal stress due to excessively rapid cooling, resulting in cracks and deformation in the molded cavity structure; if the temperature is too high, the mold material may not be able to fully solidify, leading to insufficient structural strength and stability after molding.

[0064] Step S40: Fill the cavity with the microneedle formulation and solidify it. Remove the microneedle negative mold by heating and / or dissolving to obtain the target microneedle.

[0065] In one feasible embodiment, the microneedle formulation is an active ingredient or functional material used to make microneedles. The microneedle formulation is filled into the recessed structure of a microneedle mold in an appropriate manner. The filling process needs to ensure that the formulation can uniformly fill each cavity of the microneedle mold to guarantee the quality and performance of the target microneedles. After filling, the microneedle formulation is cured and shaped by methods such as heating, light exposure, and drying. The curing process allows the formulation to form microneedles with a certain strength and shape stability. Once the microneedle formulation has completely cured, the microneedle mold is separated from the cured microneedles, ultimately yielding individual microneedle products.

[0066] In one feasible implementation, the microneedle formulation includes at least one of sodium hyaluronate, chitosan, carrageenan, pectin, konjac polysaccharide, polydimethylsiloxane, polylactic acid, and polycaprolactone.

[0067] Alternatively, biopolysaccharides such as sodium hyaluronate, chitosan, carrageenan, pectin, and konjac polysaccharide typically possess a certain degree of flexibility. After the microneedle formulation has solidified, this flexibility allows the target microneedles to undergo a certain degree of elastic deformation during demolding without easily breaking.

[0068] Optionally, polydimethylsiloxane, polylactic acid, and polycaprolactone have extremely low surface energy and weak interaction forces with the surface of the microneedle mold. After the microneedle formulation has solidified, during demolding, due to its low surface energy, the adsorption force between the formulation and the surface of the microneedle mold is small, allowing it to be easily detached from the mold, reducing demolding resistance and damage to the target microneedle structure.

[0069] Optionally, the microneedle formulation and the mold material can be different. During the microneedle fabrication process, the microneedle mold needs to be separated from the molded target microneedles. If the microneedle formulation and the mold material are the same, separation using heating or dissolution methods may affect both the microneedle formulation and the mold material simultaneously, leading to damage to the microneedle structure.

[0070] In one feasible implementation, the heating method includes at least one of infrared heating, ultrasonic heating, microwave heating and electric heating.

[0071] Alternatively, infrared heating utilizes infrared radiation to transfer heat. Infrared radiation is an electromagnetic wave; when infrared radiation shines on an object being heated, the object's molecules absorb the energy of the infrared radiation, causing them to vibrate and rotate, thereby raising the object's temperature.

[0072] Alternatively, ultrasonic heating utilizes the cavitation effect and internal friction generated when ultrasound waves propagate through a medium to produce heat. When ultrasound waves propagate in a liquid or solid, they cause the molecules of the medium to vibrate and collide violently, thereby generating heat.

[0073] Alternatively, microwave heating utilizes the interaction between microwaves and the molecules of a substance to generate heat. Microwaves are high-frequency electromagnetic waves. When microwaves irradiate a substance containing polar molecules (such as water molecules), the polar molecules vibrate and rotate rapidly with the frequency of the microwaves, and the friction between the molecules generates heat.

[0074] Alternatively, electric heating is achieved by generating Joule heat when an electric current passes through a resistive material. When an electric current passes through a heating element such as a resistance wire, the resistance wire generates heat due to its resistance, and transfers the heat to the object being heated.

[0075] In one feasible implementation, the heating temperature is 40°C to 150°C.

[0076] Optionally, the heating temperature can be 40℃, 50℃, 60℃, 70℃, 80℃, 90℃, 100℃, 110℃, 120℃, 130℃, 140℃, 150℃, etc.

[0077] Optionally, within a heating temperature range of 40℃ to 150℃, the mold material of the microneedle negative mold will melt and deform, but the microneedle formulation that has been solidified will not melt and deform. Therefore, the solidified microneedle formulation can be finally detached from the microneedle negative mold.

[0078] Alternatively, if the heating temperature is too high, it will affect the structure of the already solidified target microneedles; if the temperature is too low, the mold material will not melt smoothly, which will cause the target microneedles to be unable to detach from the microneedle mold.

[0079] Optionally, during the heating process, the state of the target microneedle tip can be observed using an optical microscope to determine whether the target microneedle has detached from the microneedle mold.

[0080] In one feasible embodiment, the solvent for dissolution includes at least one selected from petroleum ether, n-hexane, cyclohexane, toluene, xylene, and chloroform.

[0081] Alternatively, petroleum ether, n-hexane, cyclohexane, toluene, xylene, and chloroform have good solubility and can dissolve a variety of organic compounds. They are mostly liquids at room temperature and pressure, facilitating handling. They also have some volatility, allowing for the removal of solutes through evaporation. They are chemically stable and generally do not react violently with common organic compounds. They can specifically dissolve the mold material of microneedle negative molds without affecting the properties of the microneedle formulation.

[0082] In one feasible implementation, the structure of the target microneedle includes a solid structure and / or a hollow structure.

[0083] Optionally, a solid target microneedle refers to a target microneedle that is solid as a whole, without any internal hollow channels. It is usually integrally molded from a single material or composite material and has a certain strength and hardness.

[0084] Optionally, hollow-structured target microneedles refer to microneedles with hollow channels inside. The shape and size of the channels can be designed according to specific needs, so that the microneedles can not only penetrate the skin, but also inject drugs, liquids and other substances directly into the skin through the hollow channels.

[0085] The second aspect of this application provides that, after the step of removing the microneedle negative mold and obtaining the target microneedle, the method further includes: Collect the removed microneedle negative mold, remelt it and combine it with the microneedle positive mold, then cool and shape it to prepare a new microneedle negative mold.

[0086] In one feasible embodiment, during the manufacturing process of the target microneedle, after the microneedle formulation is formed within the cavity of the microneedle negative mold, the negative mold is separated from the microneedles by heating and / or dissolution, at which point the negative mold material detaches from the microneedles. The collected negative mold material is usually in a solid state (if separated by heating, it may have cooled to a solid state during collection; if separated by dissolution, it will return to a solid state after subsequent processing). To make it usable again for preparing microneedle negative molds, it needs to be remelted. The collected negative mold material is heated above its melting point by heating, transforming it into a liquid state and restoring its malleable state. The remelted negative mold material is then combined with the microneedle positive mold, which involves covering or filling the microneedle positive mold with the liquid negative mold material, enabling it to replicate the shape of the microneedle positive mold and form a cavity that matches the structure of the target microneedle. After the negative mold material and the microneedle positive mold are combined, the liquid mold material is gradually cooled and solidified by cooling molding, ultimately forming a new microneedle negative mold with the desired cavity structure, which can then be reused for microneedle manufacturing.

[0087] This embodiment reduces the raw material cost of microneedle preparation by reusing the mold material and avoids waste of resources.

[0088] In order to enable those skilled in the art to clearly understand the details and operations of the above embodiments of this application, and to demonstrate the significant improvement in performance of the embodiments of this application, the above technical solutions are illustrated below through multiple embodiments.

[0089] Example 1 Reference Figure 2A 10cm×10cm stainless steel microneedle positive mold 10 is provided and bonded to a molten microneedle negative mold mold material 20 (paraffin wax) at 60°C. The temperature is then rapidly reduced to 30°C, and the mold is demolded to separate the stainless steel microneedle positive mold 10 from the mold material 20 (paraffin wax), thereby preparing a paraffin-made microneedle negative mold 30 with an effective microneedle area of ​​10cm×10cm. 10mL of a 20%w / v hyaluronic acid (molecular weight 10,000) aqueous solution is poured into the paraffin-made microneedle negative mold 30. By vacuuming, the hyaluronic acid solution is used as microneedle formulation 40 to fill the paraffin-made microneedle negative mold 30, which is then dried. The paraffin-made microneedle negative mold 30 is further melted by heating to 75°C to obtain the target microneedles 50 arranged in an array.

[0090] Example 2 A 10cm×10cm stainless steel microneedle positive mold 10 is provided and bonded to a molten microneedle negative mold mold material 20 (paraffin wax) at 60°C. The temperature is then rapidly reduced to 30°C, and the mold is demolded to separate the stainless steel microneedle positive mold 10 from the mold material 20 (paraffin wax), thereby preparing a paraffin-made microneedle negative mold 30 with an effective microneedle area of ​​10cm×10cm. 10mL of a 20%w / v hyaluronic acid (molecular weight 10,000) aqueous solution is poured into the paraffin-made microneedle negative mold 30. By vacuuming, the hyaluronic acid solution is used as microneedle formulation 40 to fill the paraffin-made microneedle negative mold 30, which is then dried. The paraffin-made microneedle negative mold 30 is further dissolved in ether to obtain the target microneedles 50 arranged in an array.

[0091] Example 3 Reference Figure 3 A 10cm×10cm hollow stainless steel microneedle positive mold 10 is provided and bonded to a molten microneedle negative mold mold material 20 (paraffin wax) at 60°C. The temperature is then rapidly reduced to 30°C, and the mold is demolded to separate the stainless steel microneedle positive mold 10 from the mold material 20 (paraffin wax), thereby preparing a paraffin-made microneedle negative mold 30 with an effective microneedle area of ​​10cm×10cm. 10mL of a 20%w / v hyaluronic acid (molecular weight 10,000) aqueous solution is poured into the paraffin-made microneedle negative mold 30. By vacuuming, the hyaluronic acid solution is used as microneedle formulation 40 to fill the paraffin-made microneedle negative mold 30, which is then dried. The paraffin-made microneedle negative mold 30 is further melted by heating to 75°C to obtain the target microneedles 50 arranged in an array.

Claims

1. A microneedle negative mold, characterized in that, The microneedle negative mold is made of mold material and has a cavity that matches the structure of the target microneedle. After the target microneedle is formed in the cavity, the mold material of the microneedle negative mold is separated from the target microneedle by heating and / or dissolving.

2. The microneedle negative mold as described in claim 1, characterized in that, The mold material includes at least one of the following: paraffin wax, beeswax, microcrystalline wax, polyethylene wax, palm wax, ice, stearyl alcohol, low molecular weight polycaprolactone, glyceryl behenate, and lactic acid-glycolic acid copolymer.

3. A method for preparing microneedles, using the microneedle negative mold as described in claim 1 or 2, the method comprising: Microneedle positive molds are available; The molten mold material is combined with the microneedle male mold; After lamination, the microneedle mold is cooled and shaped, and then separated to obtain the microneedle negative mold, wherein a cavity matching the structure of the target microneedle is formed in the microneedle negative mold; The microneedle formulation is filled into the cavity and solidified. The microneedle negative mold is removed by heating and / or dissolving to obtain the target microneedle.

4. The method for preparing microneedles as described in claim 3, characterized in that, The heating method includes at least one of infrared heating, ultrasonic heating, microwave heating and electric heating; And / or, the solvent for dissolution includes at least one of petroleum ether, n-hexane, cyclohexane, toluene, xylene, and chloroform.

5. The method for preparing microneedles as described in claim 4, characterized in that, The heating temperature is 40℃~150℃.

6. The method for preparing microneedles as described in claim 3, characterized in that, The composite time is 20s~3600s; And / or, the temperature of the composite is 40℃~150℃; And / or, the cooling temperature is -20℃ to 30℃.

7. The method for preparing microneedles as described in claim 3, characterized in that, The microneedle material in the microneedle positive mold includes at least one of polycarbonate, polymethyl methacrylate, polydimethylsiloxane, stainless steel, aluminum alloy, copper, and chromium steel. And / or, the microneedle formulation comprises at least one of sodium hyaluronate, chitosan, carrageenan, pectin, konjac polysaccharide, polydimethylsiloxane, polylactic acid, and polycaprolactone.

8. The method for preparing microneedles as described in claim 3, characterized in that, The structure of the target microneedle includes a solid structure and / or a hollow structure.

9. The method for preparing microneedles as described in claim 3, characterized in that, After the step of removing the microneedle negative mold to obtain the target microneedle, the method further includes: The removed microneedle negative mold is collected, remelted, and combined with the microneedle positive mold, then cooled and shaped to prepare a new microneedle negative mold.

10. A microneedle prepared by the method of preparing a microneedle according to any one of claims 3 to 9.

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