Freezing microneedle auxiliary production, demolding, use or storage integrated hand tool

Abstract

The invention relates to an integrated hand tool for assisting production, demolding, use or storage of frozen microneedles, innovatively solves a plurality of technical problems encountered in the production, demolding and storage processes of the frozen microneedles by integrating a multifunctional and modular structure, and compared with the prior art, the hand tool disclosed by the invention breaks through the limitation of a traditional demolding mode, so that the production, demolding, use or storage of the frozen microneedles is facilitated. Due to the adoption of the polytetrafluoroethylene material with ultralow temperature resistance and high strength and the thermal insulation layer filled with the hydroxymethyl polymer and the water-absorbent resin, the melting speed of the frozen microneedle is effectively delayed, so that the service time window of the frozen microneedle at normal temperature is greatly prolonged, the mechanical strength of the frozen microneedle can be kept for a long time after the frozen microneedle is demoulded, and the service life of the frozen microneedle is prolonged. And the phenomenon that melting is accelerated due to contact with the body temperature of the human body is avoided, and the problems of damage and low efficiency in the traditional manual demolding process are solved.

Description

Technical Field

[0001] The present application relates to the field of medical device technology, and in particular to an integrated hand tool for assisting production, demoulding, use and storage of cryo-microneedles. Background Art

[0002] As an in vitro drug delivery carrier, microneedles are minimally invasive, painless, and have a high safety index. However, due to factors such as the load limit and small molecule limit of traditional polymer microneedles, there are still certain technical difficulties in the delivery of biological products, especially biomacromolecules, living cells, nucleic acids and other contents by microneedle products.

[0003] In order to solve the above technical problems, people have developed cryo-microneedle technology. As an emerging transdermal drug delivery treatment technology, cryo-microneedle technology can effectively deliver macromolecular drugs such as insulin, peptide drugs, and cell drugs. According to the type and load size of the delivered content, this technology adds macromolecular drugs and cryoprotectants and water or its medium mixture into a special mold, and then freezes to form microneedles with good mechanical strength. Cryo-microneedles consist of a substrate and tiny needle tips arranged in an array on it. They have mechanical strength sufficient to pierce the skin and can carry a variety of components such as drugs, nanoparticles, active substances, and even living cells. They are introduced into the subcutaneous target site by cryo-microneedles, which can significantly improve the rate and efficacy of transdermal delivery. Cryo-microneedles can melt naturally at body temperature, and the skin recovers quickly after drug administration without leaving any traces. At present, cryo-microneedles have been widely used in medical research in the fields of tumor treatment, immunotherapy, wound healing, hair growth, etc.

[0004] However, the frozen microneedles will melt rapidly at room temperature, and the mechanical strength of the frozen microneedles will decrease, resulting in the inability of the frozen microneedles to successfully penetrate the skin. Therefore, in the process of preparing frozen microneedles, the frozen microneedles need to be separated from the polydimethylsiloxane mold (i.e., PDMS mold) in a very short time without destroying the integrity of the frozen microneedles. In the related art, tweezers or fingers are used for demolding. However, in the former, due to uneven force, the needle tips of the frozen microneedles are all broken, and the broken needle tips are released from the edge to the middle. In the latter, there is obvious melting phenomenon at the place where the fingers touch the frozen microneedles, and the water droplets produced by melting increase the difficulty of demolding. The needle tips also have fractures from the edge to the center of the microneedle. Traditional frozen microneedles need to be used immediately after demolding, otherwise they will lose mechanical strength due to rapid melting, limiting their application scenarios and operational flexibility. In addition, in laboratory or clinical scenarios, the storage and short-distance transportation of frozen microneedles is a major problem. The existing technology mostly relies on low-temperature environment control, which is inconvenient to operate and has high cost. Summary of the invention

[0005] In view of the shortcomings of the prior art described above, the present invention provides an integrated hand tool for auxiliary production, demolding, use or storage of frozen microneedles, so as to solve the above-mentioned problem that in the preparation process of frozen microneedles, the frozen microneedles need to be separated from the polydimethylsiloxane mold (i.e., PDMS mold) in a very short time without destroying the integrity of the frozen microneedles. Traditional frozen microneedles need to be used immediately after demolding, otherwise they will lose mechanical strength due to rapid melting, which limits their application scenarios and operational flexibility. In addition, in laboratory or clinical scenarios, the storage and short-distance transportation of frozen microneedles is a major problem. The existing technology mostly relies on low-temperature environment control, which is inconvenient to operate and has high costs.

[0006] To achieve the above objectives, the scheme of this application is as follows:

[0007] The present application provides an integrated hand tool for assisting production, demoulding, use or storage of cryo-microneedles, including:

[0008] The shell is provided with a hollow accommodating cavity, including a cylinder and a bottom plate, wherein the bottom plate is detachably and sealably combined with the bottom of the cylinder, and the cylinder comprises an inner layer and a polytetrafluoroethylene outer layer from the inside to the outside, wherein the inner layer comprises a hydroxymethyl polymer, a water-absorbing resin or a mixture of the two;

[0009] A connector, located at the bottom of the hollow accommodating cavity, wherein a plurality of protrusions are provided at the bottom of the connector; and

[0010] A push rod, the top end of which axially passes through the cylinder, and the bottom end of which is connected to the top of the connector.

[0011] The principle of the integrated handpiece for assisting production, demoulding, use or storage of frozen microneedles in the present application is: innovatively solving multiple technical problems encountered in the production, demoulding and storage of frozen microneedles by integrating a multifunctional and modular structure. Compared with the prior art, the handpiece of the present application breaks through the limitations of traditional demoulding methods, adopts ultra-low temperature resistant and high-strength polytetrafluoroethylene material, and an insulation layer filled with hydroxymethyl polymer and water-absorbing resin inside, which effectively delays the melting speed of frozen microneedles, thereby greatly extending its use time window at room temperature, not only ensuring that the frozen microneedles can maintain their mechanical strength for a long time after demoulding, but also avoiding the phenomenon of accelerated melting due to contact with human body temperature, solving the problems of breakage and inefficiency in the traditional manual demoulding process, and greatly improving production efficiency; at the same time, the present application realizes the compatibility of production, demoulding, storage and transportation of single frozen microneedles and multiple frozen microneedles through modular design; the combination of the insulation shell and the multi-porous storage and access integrated device enables the handpiece to support the precise operation of a single microneedle, and to realize simultaneous demoulding and batch production of multiple molds, thereby improving operating efficiency and reducing the workload of experimenters. The porous storage and access device not only facilitates the short-term storage and transportation of microneedles, but also enables the rapid application of frozen microneedles in different experimental environments, meeting the different needs of scientific research and clinical sites, and further broadening the use scenarios of frozen microneedles; furthermore, the present application fills the gaps in the efficient demolding, extended operation time window and storage and transportation convenience of frozen microneedle technology, and has high efficiency, flexibility and scalability, with significant technical advantages and broad application prospects.

[0012] Optionally, the inner layer comprises a mixture of hydroxymethyl polymer and water absorbing resin.

[0013] Optionally, the mass ratio of the hydroxymethyl polymer to the water-absorbing resin is 1-2:1-2.

[0014] Specifically, in the present application, optionally, the base plate adopts a polytetrafluoroethylene base plate.

[0015] Specifically, the present application configures the bottom plate to be a polytetrafluoroethylene bottom plate, and can utilize the low-temperature resistance of the polytetrafluoroethylene material to further extend the room temperature melting time of the frozen microneedles, thereby providing ample time for experimental operations.

[0016] Optionally, the bottom plate is provided with a hollow cavity, and the hollow cavity is filled with hydroxymethyl polymer, water-absorbing resin or a mixture of the two.

[0017] Specifically, the present application effectively slows down the melting rate of the frozen microneedles by configuring the base plate to have a hollow cavity and filling the hollow cavity with hydroxymethyl polymer, water-absorbent resin or a mixture of the two, thereby greatly extending the use time window at room temperature. This not only ensures that the frozen microneedles can maintain their mechanical strength for a long time after demolding, but also avoids the phenomenon of accelerated melting due to contact with human body temperature, thereby solving the problems of breakage and inefficiency in the traditional manual demolding process.

[0018] Optionally, the hollow cavity is filled with a mixture of hydroxymethyl polymer and water-absorbing resin.

[0019] The mass ratio of the hydroxymethyl polymer to the water-absorbing resin is 1-2:1-2.

[0020] Optionally, all the protrusions are evenly distributed on the bottom of the connector.

[0021] Optionally, the protrusion is in the shape of a trapezoidal column.

[0022] Specifically, the present application can increase the bonding strength between the connector and the cryo-microneedle by configuring the protrusion to be a trapezoidal column shape, thereby further improving the demolding effect.

[0023] Optionally, the bottom end of the push rod is threadedly connected to the top of the connector.

[0024] Optionally, a handle is provided at the top of the push rod.

[0025] Specifically, the present application can improve the convenience of pulling the push rod and enhance the user experience by adding a handle at the top end of the push rod.

[0026] Optionally, the cryo-microneedle assisted production, demoulding, use or storage integrated hand tool further comprises:

[0027] A storage container having a plurality of grooves for placing the cryo-microneedle processing molds; and

[0028] A demoulding cover is detachably and sealably combined with the top of the storage container, and the demoulding cover is provided with a plurality of accommodating holes corresponding to the grooves, and the accommodating holes are used to place the connector.

[0029] It should be noted that when the frozen microneedles need to be stored, they need to be placed in a storage container, and the connector needs to be placed in the receiving hole of the demolding cover at the same time, and then the storage container together with the connector needs to be placed in a low-temperature environment (such as a refrigerator).

[0030] Specifically, the present application adds a storage container and a demoulding cover that is detachably and sealably combined with the top of the storage container. The storage container is provided with a plurality of grooves for placing the frozen microneedle processing mold, and the demoulding cover is provided with a plurality of accommodating holes corresponding to the grooves. The connector can be placed at the accommodating holes of the demoulding cover, and the PDMS mold can be directly placed in the grooves. The push rod and the cylinder are assembled, and then the push rod is fixed on the connector. Force is applied in the vertical direction to completely remove the frozen microneedle from the PDMS mold, or the push rod can be directly fixed on the connector and force is applied in the vertical direction to completely remove the frozen microneedle from the PDMS mold, that is, the storage container and The demoulding cover that is detachably and sealably combined with the top of the storage container seals and stores the frozen microneedles without the need for additional transportation, reducing the risk of sample contamination. The storage container can maintain the stability of the frozen microneedles for several hours under dry ice or refrigerated conditions to meet the transportation needs of clinical sites or different experimental sites. The storage container can be placed directly in a -80°C refrigerator to achieve long-term storage of the frozen microneedles, facilitating subsequent experiments. In addition, the storage container and the demoulding cover can be used separately as storage modules or as demoulding modules, which solves the problem of mass production and greatly improves production efficiency. That is, the components of the present application can be used separately or in modular combination to achieve multiple functions.

[0031] Optionally, the storage container is a polytetrafluoroethylene storage container.

[0032] Optionally, the demoulding cover is a polytetrafluoroethylene demoulding cover.

[0033] It should be noted that in the present application, the cryo-microneedle integrated system can include, for example, a cryo-microneedle processing system, a cryo-microneedle use system, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0035] Figure 1 This is a schematic diagram of the structure of the integrated hand tool for cryo-microneedle assisted production, demoulding, use or storage of Example 1;

[0036] Figure 2 is a schematic diagram of the structure of the connector in Example 1;

[0037] Figure 3 This is a schematic diagram of the structure of the storage container 4 and demoulding cover 5 of the integrated hand tool for cryo-microneedle assisted production, demoulding, use or storage in Example 2;

[0038] Figure 4 A diagram showing the use status of the integrated hand tool for assisting production, demoulding, use or storage of cryo-microneedles in Example 2 (the cryo-microneedles are not removed from the mold);

[0039] Figure 5 This is a diagram of the use status of the integrated hand tool for assisting production, demoulding, use or storage of cryo-microneedles in Example 2 (the cryo-microneedles have been removed from the mold).

[0040] Figure 6 This is a diagram of the use status of the integrated handpiece for assisted production, demoulding, use or storage of cryo-microneedles in Example 2 (the cryo-microneedles have been removed from the mold and applied to test animals).

[0041] Reference numerals

[0042] 1-shell, 11-hollow accommodating chamber, 111-inner layer, 112-polytetrafluoroethylene outer layer, 12-cylinder, 13-bottom plate;

[0043] 2-connector, 21-protrusion;

[0044] 3-putter, 31-handle;

[0045] 4- storage container, 41- groove;

[0046] 5- demoulding cover, 51- receiving hole;

[0047] 6- Cryo-microneedling;

[0048] 7-PDMS mold. DETAILED DESCRIPTION

[0049] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0050] It should be noted that all directional indications in the embodiments of the present invention (such as up, down, left, right, front, back, top, bottom, inside, outside...) are only used to explain the relative position relationship, movement status, etc. between the components in a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0051] In the present invention, unless otherwise clearly specified and limited, the terms "connection", "fixation", etc. should be understood in a broad sense. For example, "fixation" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0052] In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the fact that ordinary technicians in the field can implement it. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0053] In the related art, tweezers or fingers are used for demolding. However, in the former, due to uneven force, the tips of the frozen microneedles are broken, and the broken tips are released from the edge to the middle. In the latter, there is obvious melting phenomenon at the place where the fingers touch the frozen microneedles, and the water droplets produced by melting increase the difficulty of demolding. The tips of the needles are also broken from the edge to the center of the microneedle. Traditional frozen microneedles need to be used immediately after demolding, otherwise they will lose mechanical strength due to rapid melting, which limits their application scenarios and operational flexibility. In addition, in laboratory or clinical scenarios, the storage and short-distance transportation of frozen microneedles is a major problem. Existing technologies mostly rely on low-temperature environment control, which is inconvenient to operate and has high costs.

[0054] Based on the above technical problems, an embodiment of the present application provides an integrated hand tool for assisting production, demoulding, use or storage of cryo-microneedles, including:

[0055] The shell 1 is provided with a hollow accommodating chamber 11, including a cylinder 12 and a bottom plate 13, the bottom plate 13 is detachably and sealably combined with the bottom of the cylinder 12, the cylinder 11 includes an inner layer 111 and a polytetrafluoroethylene outer layer 112 from the inside to the outside, the inner layer 111 includes a hydroxymethyl polymer, a water-absorbing resin or a mixture of the two, the bottom plate 13 is a polytetrafluoroethylene bottom plate, the bottom plate 13 is provided with a hollow cavity, and the hollow cavity is filled with a hydroxymethyl polymer, a water-absorbing resin or a mixture of the two;

[0056] The connector 2 is located at the bottom of the hollow accommodating cavity 11. A plurality of protrusions 21 are evenly arranged on the bottom of the connector 2. The protrusions 21 are in the shape of trapezoidal columns; and

[0057] The push rod 3 has its top end axially extending out of the cylinder 12 , and its bottom end is threadedly connected to the top of the connector 2 . A handle 31 is provided at the top of the push rod.

[0058] In another embodiment of the present application, the integrated hand tool for auxiliary production, demolding, use or storage of cryo-microneedles also includes: a storage container 4 and a demolding cover 5 detachably and sealably combined with the top of the storage container 4, the storage container 4 is provided with a plurality of grooves 41 for placing the cryo-microneedle processing mold, the demolding cover 5 is provided with a plurality of accommodating holes 51 corresponding to the grooves 41, the accommodating holes 51 are used to place the connector 2, the storage container 4 is a polytetrafluoroethylene storage container, and the demolding cover 5 is a polytetrafluoroethylene demolding cover.

[0059] In the following description, numerous details are discussed to provide a more thorough explanation of embodiments of the present invention; however, it is apparent to one skilled in the art that embodiments of the present invention may be practiced without these specific details.

[0060] Example 1

[0061] See also Figure 1 , Figure 1 The integrated handpiece for auxiliary production, demoulding, use or storage of cryo-microneedles of this embodiment includes a shell 1 , a connector 2 and a push rod 3 .

[0062] See also Figure 1The shell 1 is provided with a hollow accommodating chamber 11, the shell includes a cylinder 12 and a bottom plate 13, the bottom plate 13 is detachably and sealably combined with the bottom of the cylinder 12, the cylinder 11 includes an inner layer 111 and a polytetrafluoroethylene outer layer 112 from the inside to the outside, the inner layer 111 includes a hydroxymethyl polymer, a water-absorbing resin or a mixture of the two, the bottom plate 13 adopts a polytetrafluoroethylene bottom plate, the bottom plate 13 is provided with a hollow cavity, and the hollow cavity is filled with a hydroxymethyl polymer, a water-absorbing resin or a mixture of the two. If the inner layer includes a mixture of a hydroxymethyl polymer and a water-absorbing resin, the mass ratio of the hydroxymethyl polymer to the water-absorbing resin is 1-2:1-2, and if the hollow cavity is filled with a mixture of a hydroxymethyl polymer and a water-absorbing resin, the mass ratio of the hydroxymethyl polymer to the water-absorbing resin is 1-2:1-2. Examples of hydroxymethyl polymers include hydroxymethyl cellulose (HPC), hydroxymethyl starch (HES), hydroxymethyl polyvinyl alcohol (HEC), and hydroxymethyl polyacrylic acid (HPM). Examples of water-absorbing resins include sodium polyacrylate (Sodium polyacrylate), polyacrylamide (PAM), polyvinyl alcohol / polyvinyl amine composite (PVA / PEA composite), polyurethane, and natural seaweed (Sodium alginate).

[0063] Specifically, this embodiment effectively slows down the melting rate of the frozen microneedles by configuring the cylinder 11 to include, from the inside to the outside, an inner layer 111 and a polytetrafluoroethylene outer layer 112, wherein the inner layer includes a hydroxymethyl polymer, a water-absorbing resin or a mixture of the two. This greatly extends the use time window at room temperature, and not only ensures that the frozen microneedles can maintain their mechanical strength for a long time after demolding, but also avoids the phenomenon of accelerated melting due to contact with human body temperature, thereby solving the problems of breakage and inefficiency in the traditional manual demolding process.

[0064] Please continue reading Figure 1 The top end of the push rod 3 axially passes through the cylinder 12, the bottom end of the push rod 3 is threadedly connected to the top of the connector 2, and a handle 31 is provided at the top of the push rod.

[0065] Specifically, this embodiment can improve the convenience of pulling the push rod 3 and enhance the user experience by adding a handle 31 at the top of the push rod 3.

[0066] See also Figure 1 and Figure 2The connector 2 is located on the inner bottom side of the hollow accommodating cavity 11, and a plurality of protrusions 21 are evenly arranged on the bottom of the connector 2. The protrusions 21 are trapezoidal column-shaped, and the protrusions 21 are used to fix the cryo-microneedle and the connector 2 together, so that the cryo-microneedle can be pulled out of the polydimethylsiloxane mold (i.e., the PDMS mold) by a push rod threadedly connected to the top of the connector 2.

[0067] Specifically, in this embodiment, by configuring the protrusion 21 to be a trapezoidal column, the bonding strength between the connector and the cryo-microneedle can be increased, thereby further improving the demolding effect.

[0068] The principle of the integrated handpiece for assisted production, demoulding, use or storage of frozen microneedles in this embodiment is as follows: innovatively solving multiple technical problems encountered in the production, demoulding and storage of frozen microneedles by integrating a multifunctional and modular structure. Compared with the prior art, the handpiece of this application breaks through the limitations of traditional demoulding methods, and adopts a polytetrafluoroethylene material that is resistant to ultra-low temperatures and has high strength, and an insulation layer filled with hydroxymethyl polymer and water-absorbing resin, which effectively delays the melting rate of the frozen microneedles, thereby greatly extending their use time window at room temperature, which not only ensures that the frozen microneedles can maintain their mechanical strength for a long time after demoulding, but also avoids the phenomenon of accelerated melting due to contact with human body temperature, solving the problems of breakage and inefficiency in the traditional manual demoulding process; at the same time, this application adopts a modular design. The design realizes the compatibility of production, demoulding, storage and transportation of single and multiple frozen microneedles; the combination of the heat-insulating shell and the porous storage-and-access integrated device enables the handpiece to support the precise operation of a single microneedle and realize the simultaneous demoulding and batch production of multiple molds, thereby improving the operation efficiency and reducing the workload of the experimenters; the porous storage-and-access integrated device is not only convenient for the short-term storage and transportation of microneedles, but also realizes the rapid application of frozen microneedles in different experimental environments, meets the different needs of scientific research and clinical sites, and further broadens the use scenarios of frozen microneedles; in addition, the present application fills the gaps in the frozen microneedle technology in terms of efficient demoulding, extended operation time window and convenience of storage and transportation, has high efficiency, flexibility and scalability, and has significant technical advantages and broad application prospects.

[0069] Example 2

[0070] See also Figure 3 The difference between this embodiment and embodiment 1 is that it also includes a storage container 4 and a demoulding cover 5 that is detachably and sealably combined with the top of the storage container 4.

[0071] Please continue reading Figure 3, a storage container 4 and a demoulding cover 5 which is detachably and sealably combined with the top of the storage container 4, the storage container 4 is provided with a plurality of grooves 41 for placing the frozen microneedle processing mold, the demoulding cover 5 is provided with a plurality of accommodating holes 51 corresponding to the grooves 41, the accommodating holes 51 are used to place the connector 2, the storage container 4 is a polytetrafluoroethylene storage container, and the demoulding cover 5 is a polytetrafluoroethylene demoulding cover.

[0072] Specifically, the present embodiment adds a storage container 4 and a demoulding cover 5 which is detachably and sealably combined with the top of the storage container 4. The storage container 4 is provided with a plurality of grooves 41 for placing the frozen microneedle processing mold, and the demoulding cover 5 is provided with a plurality of accommodating holes corresponding to the grooves 41. The connector 2 can be placed at the accommodating hole 51, and the PDMS mold 7 can be directly placed in the groove 41. The push rod 3 and the cylinder are assembled, and then the push rod 3 is fixed on the connector 2. Force is applied in the vertical direction to completely remove the frozen microneedle 6 from the PDMS mold 7. Alternatively, the push rod 3 can be directly fixed on the connector 2 and force is applied in the vertical direction to completely remove the frozen microneedle 6 from the PDMS mold 7, that is, it can be removed by The storage container 4 and the demoulding cover 5 detachably and sealably combined with the top of the storage container 4 seal and store the frozen microneedles 6 without the need for additional transportation, thereby reducing the risk of sample contamination. The storage container can maintain the stability of the frozen microneedles for several hours under dry ice or refrigerated conditions to meet the transportation needs of clinical sites or different experimental sites. The storage container can be placed directly in a -80°C refrigerator to achieve long-term storage of the frozen microneedles, facilitating subsequent experiments. In addition, the storage container and the demoulding cover can be used separately as storage modules or as demoulding modules, which solves the problem of mass production and greatly improves production efficiency. That is, the components of the present application can be used separately or in modular combination to achieve multiple functions.

[0073] The method of using the integrated hand tool of this embodiment is as follows:

[0074] When preparing the frozen microneedle 6, the microneedle matrix is ​​added to the PDMS mold, and the liquid surface is kept flat, the connector 2 is placed on the PDMS mold, and the protrusion 21 at the bottom of the connector 2 is kept immersed in the microneedle matrix, and then the PDMS mold and the connector 2 are subjected to gradient freezing;

[0075] After freezing, the microneedle matrix changes from a liquid state to a hard solid state, and the protrusion 21 at the bottom of the connector 2 is fixed in the solid frozen microneedle 6. The push rod 2 and the barrel 12 are assembled (if necessary), and then the push rod 2 is screwed onto the connector 2, and force is applied in the vertical direction to completely remove the frozen microneedle 6 from the PDMS mold 7 (such as Figure 4 and Figure 5 As shown), the push rod 2 can also be directly screwed onto the connector 2 and force can be applied in the vertical direction to completely remove the frozen microneedle 6 from the PDMS mold 7;

[0076] Immediately after demoulding, the cryo-microneedles 6 are applied vertically to the skin surface for transdermal use (e.g. Figure 6 shown).

[0077] Demolding is performed in the manner of this embodiment (the inner layer is formed by a mixture of hydroxymethyl cellulose and sodium polyacrylate in a mass ratio of 1:1, and the hollow cavity is filled with a mixture of hydroxymethyl cellulose and sodium polyacrylate in a mass ratio of 1:1). The entire process from taking out the frozen microneedle 6 from the PDM mold to actual application can be controlled within 15 seconds. Since the frozen microneedle 6 does not come into contact with the operator throughout the process, the technical problem of melting due to body temperature is avoided. The number of broken microneedles accounts for about 8% (taking 100 microneedle samples as an example), and the number of microneedles with incomplete needle tips accounts for about 15% (taking 100 microneedle samples as an example).

[0078] Comparative Example 1

[0079] Use tweezers to demould, specifically:

[0080] The frozen microneedles were taken out of the -80°C refrigerator and immediately picked out of the PDMS mold with tweezers. The tweezers were used to remove the frozen microneedles from the mold for 5 times. The average demolding time was about 15 seconds. The frozen microneedles showed signs of melting at room temperature, and there were 3 cracks on the base of the microneedles when they were taken out with tweezers. In the 5 demolding processes, the tips of the frozen microneedles were broken due to uneven force, and most of the broken tips spread from the edge to the middle. The number of broken microneedles accounted for about 30% (taking 100 microneedle samples as an example), and the number of microneedles with incomplete tips accounted for about 50% (taking 100 microneedle samples as an example).

[0081] Comparative Example 2

[0082] Use fingers to demould, specifically:

[0083] The operator demolded the microneedles by hand 5 times, specifically: after taking the frozen microneedles out from -80℃, he immediately put on gloves and used the thumb and index finger to fix the PDMS mold, and used the other hand to pick out the frozen microneedles. The average demolding time was about 20s, and there was obvious melting at the point where the fingers touched the frozen microneedles, and the water droplets produced by the melting increased the difficulty of demolding. The needle tips also had fractures from the edge to the center of the microneedle, and the broken needle tips accounted for about , the number of broken microneedles accounted for about 40% (taking 100 microneedle samples as an example), and the number of microneedles with incomplete needle tips accounted for about 60% (taking 100 microneedle samples as an example).

[0084] In summary, the integrated hand tool of the present application is used for demoulding. After demoulding, the low temperature state of the frozen microneedles can be effectively maintained by the shell 1, and the melting time of the frozen microneedles 6 is extended from 2 minutes of traditional technology to more than 10 minutes. The extended time window provides greater fault tolerance and flexibility for experimental operations, ensuring that the frozen microneedles 6 can maintain ideal performance under different experimental conditions, significantly improving the success rate of the experiment. After demoulding, the frozen microneedles 6 can be directly applied to the mouse skin, thereby achieving fast and smooth operation from mold removal to practical application. At the same time, the microneedles can be temporarily stored in the storage container 4 to further delay melting, provide ample time for subsequent experiments, and do not require additional transfer, reducing the risk of sample contamination. The storage container 4 can maintain the stability of the frozen microneedles for several hours, which is suitable for the transportation needs of clinical sites or different experimental sites. The storage container 4 can be placed directly in a -80°C refrigerator to achieve long-term storage of frozen microneedles, which is convenient for subsequent experiments.

[0085] In summary, this application not only greatly improves the demoulding efficiency of cryo-microneedles, but also significantly extends the operation time window. At the same time, through convenient storage and transportation design, it solves the key problems in the practical application of cryo-microneedles. This application is an important innovation in the field of cryo-microneedles, providing more efficient and flexible technical support for scientific research and clinical applications.

[0086] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the technology may modify or change the above embodiments without violating the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by a person of ordinary skill in the art without departing from the spirit and technical ideas disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. A hand tool for assisting production, demoulding, use or storage of cryo-microneedles, characterized in that: include: The shell is provided with a hollow accommodating cavity, including a cylinder and a bottom plate, the bottom plate is detachably and sealably combined with the bottom of the cylinder, the cylinder includes an inner layer and a polytetrafluoroethylene outer layer from the inside to the outside, the inner layer includes a hydroxymethyl polymer, a water-absorbing resin or a mixture of the two, and the bottom plate is detachably and sealably combined with the bottom of the cylinder; A connector, located at the bottom of the hollow accommodating cavity, wherein a plurality of protrusions are provided at the bottom of the connector; and A push rod, the top end of which axially passes through the cylinder, and the bottom end of which is connected to the top of the connector.

2. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 1, characterized in that: The inner layer includes a mixture of a methylol polymer and a water-absorbing resin.

3. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 2, characterized in that: The mass ratio of the hydroxymethyl polymer to the water-absorbing resin is 1-2:1-2.

4. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 1, characterized in that: The bottom plate is provided with a hollow cavity, and the hollow cavity is filled with hydroxymethyl polymer, water-absorbing resin or a mixture of the two.

5. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 1, characterized in that: All the protrusions are evenly distributed on the bottom of the connector.

6. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 1, characterized in that: The protrusion is in a trapezoidal column shape.

7. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 1, characterized in that: The bottom end of the push rod is threadedly connected to the top of the connector.

8. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 1, characterized in that: Also includes: A storage container having a plurality of grooves for placing the cryo-microneedle processing mold; and A demoulding cover is detachably and sealably combined with the top of the storage container, and the demoulding cover is provided with a plurality of accommodating holes corresponding to the grooves, and the accommodating holes are used to place the connector.

9. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 8, characterized in that: The storage container is a polytetrafluoroethylene storage container.

10. The cryo-microneedle assisted production, demoulding, use or storage integrated hand tool according to claim 8, characterized in that: The demoulding cover is a polytetrafluoroethylene demoulding cover.

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