Gasket for soluble microneedle patch, application of gasket, microneedle patch and preparation method of microneedle patch

Abstract

The invention discloses a gasket for a soluble microneedle patch, application of the gasket, the microneedle patch and a preparation method, and belongs to the technical field of microneedle preparation, the contact angle of the gasket is 30-70 degrees, and the gasket is subjected to electron irradiation treatment. The application refers to application of the gasket in preparation of a soluble microneedle patch, and the microneedle patch contains the gasket. The gasket with the contact angle of 30-70 degrees is obtained through hydrophilic treatment, electron beam irradiation treatment is carried out on the gasket, the combination stability of the gasket and the microneedle substrate is improved, and therefore it is guaranteed that the microneedle can be stably combined to the gasket within the period of validity. Compared with the prior art, a viscous material does not need to be used, the problem that in the long-term existing process, the viscous material and active ingredients on the microneedle are mutually infiltrated is solved, the stability of the microneedle active material is improved, and the administration accuracy of the microneedle is also guaranteed.

Description

Technical Field

[0001] The present invention belongs to the technical field of microneedle preparation, and particularly relates to a gasket for a soluble microneedle patch, an application thereof, the soluble microneedle patch and a preparation method thereof. Background Art

[0002] A microneedle patch includes an adhesive layer and microneedles adhered to the adhesive layer, or an adhesive layer and a non-adhesive microneedle substrate adhered to the adhesive layer, and the microneedles are disposed on the microneedle substrate. The adhesive layer generally uses a hydrophobic material with an adhesive, and the microneedles or the microneedle substrate are adhered to the adhesive material. However, generally, the shelf life of microneedles is 2-3 years. In the case of long-term storage, the adhesive material and the active ingredient on the microneedles are likely to penetrate each other, thereby affecting the stability of the active material of the microneedles and also affecting the dosing accuracy of the microneedles.

[0003] CN216258729U discloses a microneedle patch, which includes a base layer, a gasket and a plurality of soluble microneedles. The adhesion surface of the base layer can adhere to the skin surface. The gasket is disposed on the adhesion surface of the base layer, and the plurality of soluble microneedles are disposed on the end surface of the gasket away from the base layer. However, the soluble microneedles are still adhered to the base or the gasket through an adhesive material, and there is still a problem that the adhesive material and the active ingredient on the microneedles are likely to penetrate each other. CN216258728U discloses a microneedle patch, which includes a base layer, an adhesive layer, a magnetic member and a plurality of soluble microneedles. One end of the soluble microneedles of this invention is adhered to the magnetic member through an adhesive layer. The soluble microneedles are still adhered to the base or the gasket through an adhesive material, and there is still a problem that the adhesive material and the active ingredient on the microneedles are likely to penetrate each other.

[0004] In summary, at present, in order to stably connect the gasket with the soluble microneedle substrate, it is necessary to bond the gasket and the microneedle substrate through an adhesive material. However, when the microneedles or the microneedle substrate are adhered to the adhesive material, in the case of long-term storage, the adhesive material and the active ingredient on the microneedles are likely to penetrate each other, thereby affecting the stability of the active material of the microneedles and also affecting the dosing accuracy of the microneedles. Therefore, it is urgent to develop a gasket without an adhesive material, which is of great significance to the field of microneedle preparations. Summary of the Invention

[0005] In order to solve the above technical problems, the present invention provides a gasket for a soluble microneedle patch, an application thereof, the soluble microneedle patch and a preparation method thereof. The present invention uses a hydrophilic treatment to obtain a gasket with a contact angle of 30-70°, and performs electron beam irradiation treatment on it, which increases the binding stability between the gasket and the microneedle substrate, thereby ensuring that the microneedles can be stably bound to the gasket within the shelf life.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a gasket for a soluble microneedle patch, the contact angle of the gasket being 30 - 70°, and the gasket being treated by electron irradiation.

[0008] Preferably, the contact angle of the gasket is 30 - 55°, more preferably 30 - 45°; even more preferably 30 - 37°.

[0009] In the present invention, the electron irradiation treatment is: intensity 7 - 14 kGy, treatment speed 2 - 5 m / min.

[0010] The gasket of the present invention is made of any one or a mixture of at least one of thermoplastic polyurethane, polypropylene, polycarbonate, and acrylonitrile - butadiene - styrene copolymer; preferably thermoplastic polyurethane elastomer rubber (TPU).

[0011] The gasket of the present invention can be subjected to a hydrophilic treatment well - known in the art to change the hydrophilicity of the gasket surface so that it has a contact angle of 30 - 70°, such as plasma treatment.

[0012] In some specific hydrophilic treatments, when the plasma power is 400 - 600 W, the distance between the plasma nozzle and the gasket is 2 - 8 mm, and the moving speed of the plasma nozzle is 30 - 80 mm / s, this condition can stably achieve a contact angle of the gasket of 45 - 70°, and the gasket is not easily blown off at this power, but the hydrophilicity of the gasket surface can only be maintained for 24 - 36 h. When the distance or speed is increased, the contact angle of the gasket will be greater than 70°, and stable microneedle separation cannot be achieved. When the distance or speed is decreased, the surface of the gasket is damaged and cannot be used for microneedle preparation.

[0013] In some specific hydrophilic treatments, when the plasma power is 600 - 800 W, the distance between the plasma nozzle and the gasket is 3 - 12 mm, and the speed of the plasma nozzle is 60 - 150 mm / s, this condition can stably achieve a contact angle of the gasket of 30 - 70°, maintain high - efficiency separation stability, and the hydrophilic time - effectiveness of the gasket can be maintained for 72 h. When the distance or speed is increased, the contact angle of the gasket will be greater than 70°, and stable microneedle separation cannot be achieved. When the distance or speed is decreased, the surface of the gasket is damaged and cannot be used for microneedle preparation. At the same time, the contact angle of the gasket will also decrease, less than 30°, reducing the microneedle separation stability.

[0014] In certain specific hydrophilic treatments, when the plasma power is 800 - 1000 W, the distance between the plasma nozzle and the gasket is 10 - 20 mm, and the speed of the plasma nozzle is 80 - 200 mm / s, this condition can stably achieve a contact angle of the gasket between 30 - 70°, maintain high separation stability, and the hydrophilic timeliness of the gasket can be maintained for 72 h. When the distance or speed is reduced, the contact angle of the gasket decreases (less than 30°), the separation stability of micro - needle preparation decreases, and it is also easy to blow the gasket over or damage the surface of the gasket. When the distance or speed is increased, the contact angle of the gasket increases (greater than 70°), and stable micro - needle separation cannot be achieved.

[0015] Further preferably, the hydrophilic treatment method adopted in the present invention is as follows: when the plasma power is 400 - 600 W, the distance between the plasma nozzle and the gasket is 2 - 8 mm, and the moving speed of the plasma nozzle is 30 - 80 mm / s, the contact angle of the gasket obtained is 45 - 55°; or

[0016] when the plasma power is 650 - 800 W, the distance between the plasma nozzle and the gasket is 3 - 12 mm, and the speed of the plasma nozzle is 60 - 150 mm / s, the contact angle of the gasket obtained is 30 - 55°; or

[0017] when the plasma power is 830 - 1000 W, the distance between the plasma nozzle and the gasket is 10 - 20 mm, and the speed of the plasma nozzle is 80 - 200 mm / s, the contact angle of the gasket obtained is 30 - 50°.

[0018] The elasticity of the gasket described in the present invention is sufficient to resist the deformation that occurs during micro - needle separation. Preferably, the elasticity of the gasket > 0.5 N. When the elasticity of the gasket is lower than 0.5 N, it cannot resist the force of deformation that occurs during micro - needle separation, resulting in micro - needle breakage.

[0019] The thickness of the gasket in the present invention is sufficient to achieve the separation of micro - needles from the micro - needle mold and ensure that the prepared micro - needle patch does not affect its use and can be effectively fixed on the skin surface. Preferably, the thickness of the gasket is 0.1 - 150 mm. When the thickness is less than 0.1 mm, it is not conducive to separation and cannot effectively separate the micro - needles from the micro - needle mold; when the thickness is greater than 150 mm, it is not conducive to the use of the micro - needle patch and cannot be effectively fixed on the skin surface.

[0020] In the second aspect, the present invention provides the application of the above - mentioned gasket in the preparation of soluble micro - needle patches.

[0021] In the third aspect, the present invention provides a soluble micro - needle patch containing the aforementioned gasket.

[0022] The soluble micro - needle patch in the present invention includes a gasket and soluble micro - needles provided on the gasket.

[0023] Fourthly, the present invention provides a method for preparing a soluble microneedle patch containing the gasket, which comprises the following steps: laminating the gasket with the microneedle substrate, drying, and demolding.

[0024] In the present invention, the viscous microneedle substrate has raised droplets. Preferably, the volume of the raised droplets is: πr 3 -2 / 3π(r + d / 2) 3 , where r is the radius of the microneedle substrate on the surface of the microneedle mold, and d is the distance between the centers of adjacent microneedle substrates on the surface of the microneedle mold.

[0025] In the present invention, the material of the raised droplets is a soluble microneedle solution. Specifically, the soluble microneedle solution contains a soluble microneedle skeleton material, and the soluble microneedle skeleton material is a conventional soluble microneedle skeleton material in the art. Those skilled in the art can select according to actual needs. For example, the soluble microneedle skeleton material can be selected from at least one of polyester, polyhydroxyalkanoate, copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate, polyacrylamide, modified polypropylene, polyhydroxyalkanoate-polyethylene glycol, poly-α-hydroxy acid, poly-β-hydroxy acid, polyhydroxybutyrate, polyester amide, polycaprolactone, polylactide, polyglycolic acid, polydioxanone, polyorthoester, polyether ester, polyanhydride, glycolic acid-trimethylenecarbonate copolymer, polyphosphate, polyphosphate urethane, polyamino acid, polycyanoacrylate, polytrimethylenecarbonate, polycarbonate, polyphosphocreatine, chitosan, dextran, heparin, hyaluronic acid, sucrose, trehalose, mannitol, chondroitin sulfate, Tween 80, gelatin, poly(lactic-co-glycolic acid), polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, sodium alginate, maltose, hydroxypropyl-β-cyclodextrin, polylactic acid, polyethylene glycol, glycerol, sodium chloride, inulin, starch, and glycogen. The mass percentage ratio of the soluble microneedle solution in the present invention is less than 30%, preferably 30%-50%.

[0026] Preferably, the preparation method comprises the following steps:

[0027] (1) Filling the soluble microneedle solution into the microneedle mold to form raised droplets, and performing semi-drying treatment;

[0028] (2) Laminating the gasket with the raised droplets by pressing, drying, and demolding.

[0029] More preferably, the semi-drying treatment in step (1) is: placing at a humidity of 75%-98% and a temperature not lower than 10°C for 10 min - 12 h, and then placing at a humidity of 30%-80% and a temperature of 20 - 45°C for 2 min - 60 min.

[0030] Further preferably, the pressure for lamination in step (2) is 1-5 N per square centimeter.

[0031] Further preferably, the drying in step (2) is as follows: drying at a humidity of 10%-90% and a temperature of 20-30 °C for 5-72 h.

[0032] The beneficial effects of the present invention are as follows:

[0033] (1) The present invention uses a hydrophilic treatment to obtain a gasket with a contact angle of 30-70°, and performs an electron beam irradiation treatment on it, increasing the binding stability between the gasket and the microneedles. The adsorption force between the microneedles and the gasket is high, and the demolding yield rate of the prepared microneedles is high and the separation stability is excellent.

[0034] (2) The gasket of the present invention has good hydrophilicity and timeliness, and the binding strength between the gasket and the microneedles is high, ensuring that the microneedles can be stably bound to the gasket within the validity period and still meet the requirements after long-term storage.

[0035] (3) Compared with the prior art, the present invention does not need to use an adhesive material, realizes the stable binding between the gasket and the soluble microneedle substrate, avoids the problem of mutual penetration between the adhesive material and the active ingredient on the microneedles during the long-term existence process, improves the stability of the microneedle active material, and also ensures the drug delivery accuracy of the microneedles. Description of the Drawings

[0036] Figure 1 It is a film puncture diagram of the microneedle patch after aging in the example. Among them, A is the situation of the microneedle patch piercing into the film, and B is the morphology after the microneedle patch pierces into the film.

[0037] Figure 2 It is a film puncture diagram of the microneedle patch after aging in the comparative example. Among them, A is the situation of the microneedle patch piercing into the film, and B is the morphology after the microneedle patch pierces into the film. Detailed Embodiments

[0038] The following specific examples illustrate the implementation manners of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific implementation manners, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0039] Before further describing the specific implementation manners of the present invention, it should be understood that the protection scope of the present invention is not limited to the specific implementation manners described below; it should also be understood that the terms used in the embodiments of the present invention are for the purpose of describing specific implementation manners and are not intended to limit the protection scope of the present invention.

[0040] When numerical ranges are given in the embodiments, it should be understood that unless otherwise specified in the present invention, both endpoints of each numerical range and any value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention pertains.

[0041] The present invention does not limit the sources of the raw materials used. Unless otherwise specified, the raw materials used in the present invention are all ordinary commercially available products in this technical field. Unless otherwise specified, the "microneedle patch", "microneedle patch", and "soluble microneedle patch" mentioned in the present invention have the same meaning, the "base", "microneedle base" mentioned have the same meaning, and the "microneedle" and "hemolytic microneedle" mentioned have the same meaning.

[0042] Testing methods

[0043] 1. Contact angle measurement

[0044] Turn on the contact angle measuring instrument (model: SDC-100). Place the plasma-treated gasket on the fixed platform of the contact angle measuring instrument. Then, adjust the special injection syringe of the instrument filled with pure water to place a specific liquid drop at the needle tip, and then slowly transfer the liquid drop to the surface of the gasket. Then, display the liquid drop at a specific position in the measurement software, and then press the Enter key on the computer to measure, and finally generate a report for export.

[0045] 2. Adsorption force measurement

[0046] Fix the microneedle gasket vertically on a plane, and then use a pressure tester to move vertically downward with respect to the microneedles. The microneedles are detached from the gasket by the downward force to obtain the adsorption force between the microneedles and the gasket.

[0047] 3. Separation stability

[0048] Use TPU gaskets to prepare microneedle patches three times (100 patches each time), and then separate the microneedles to count the number of completely separated microneedle patches and calculate the yield rate of the completely separated good products. Then calculate the average yield rate of the three separations to represent the separation stability.

[0049] 4. Microneedle patch piercing film test

[0050] Cut a 2-5 cm square sealing film, and then place it on a flat PDMS (elastic silicone plate). Place the microneedle patch with the needle tip facing down on the film, and use a vertically downward force to press the patch to pierce the film. Then separate the patch from the film, and use a microscope to observe the morphology of the microneedles after piercing and whether they have pierced the film.

[0051] 5. Elasticity test

[0052] Place the TPU gasket horizontally on a flat surface and slowly move it downward using a pressure tester, and record the force that causes the gasket to deform.

[0053] The soluble microneedles include a microneedle base, a needle column connected to the microneedle base, and a needle tip at one end of the needle column far from the microneedle base. The drug-loading end of the soluble microneedles is located at the needle tip and the end of the needle column close to the needle tip. The length of the microneedles is 200 - 1200 μm, so that the drug-loading end of the soluble microneedles can be effectively delivered to the dermis layer. To increase the contact area between the soluble microneedles and the gasket, the microneedle base is generally frustum-shaped.

[0054] The soluble microneedle patch includes a gasket and soluble microneedles directly disposed on the gasket. The gasket that is not sticky and has a contact angle of 30 - 70° after hydrophilic treatment is bonded to the microneedle base of the soluble microneedles after electron irradiation treatment (intensity 7 - 14 kGy, treatment speed 2 - 5 m / min), and then dried and demolded.

[0055] Next, examples and comparative examples of the present invention are shown to explain the performance of the gasket of the present invention in more detail, but the present invention is not limited thereto.

[0056] [Examples 1 - 16, Comparative Examples 1 - 7]

[0057] Prepare the soluble microneedle patch according to the following preparation method according to Table 1

[0058] (1) Fill the soluble microneedle solution (35 wt% dextran solution) into the microneedle mold to form a raised droplet on the surface of the microneedle mold, and control the volume of the raised droplet to 2 / 3π(r + d / 2) 3 , and place it for 20 min at a humidity of 85% and a temperature of 12°C, and then place it for 10 min at a humidity of 80% and a temperature of 30°C for semi-drying treatment;

[0059] (2) Bond the TPU gasket (thickness 5 mm, elastic force 0.6 N) to the raised droplet, press it with a force of 3 N per square centimeter to make the gasket form an effective contact area, and dry it at a humidity of 60% and 25°C for 24 h, and then demold to obtain the soluble microneedle patch.

[0060] Table 1

[0061]

[0062]

[0063]

[0064] As can be seen from the microneedle patches prepared in Examples 1-16, the TPU gaskets provided by the present invention are treated by plasma and electron beam irradiation. The qualified rate of demolding of the prepared TPU gaskets is 98%-100%, the adsorption force between the microneedles and the TPU gaskets is 1.12-2.16 N, and the separation stability is 98%-100%. In Comparative Example 7, the conventional TPU gasket has a poor bonding force with the microneedles and cannot be demolded after drying.

[0065] As can be seen from the comparison of the microneedle patches prepared in Example 16 and Comparative Examples 1-3, when the contact angle of the TPU gasket exceeds 70°, the qualified rate of demolding drops to 64%-75%, the adsorption force between the microneedles and the TPU gasket drops to 0.37-0.50 N, and the separation stability drops to 65%-75%.

[0066] As can be seen from the comparison of the microneedle patches prepared in Example 12 and Comparative Example 4 and the comparison of the microneedle patches prepared in Example 14 and Comparative Example 5, when the TPU gasket lacks electron beam treatment, the qualified rate of demolding, the adsorption force between the microneedles and the TPU gasket, and the separation stability all decrease.

[0067] As can be seen from the comparison of the microneedle patches prepared in Example 3 and Comparative Example 6, when the parameters of the electron beam treatment are changed, it has a great influence on the adsorption force between the microneedles and the TPU gasket.

[0068] [Stability of the microneedle patch within the validity period]

[0069] The microneedle patches prepared in the above-mentioned examples and comparative examples were subjected to aging treatment to investigate the stability and effectiveness of the microneedle patches within the validity period. The results are shown in Table 2.

[0070] Table 2

[0071]

[0072]

[0073] The packaged microneedles were freely dropped from the same height (1 m from the ground). When the effective adsorption force between the microneedles and the gasket is greater than 0.3 N, the microneedles on the microneedle patch are completely preserved. When the adsorption force is less than 0.3 N, the microneedles are easily detached from the gasket. Therefore, when the adsorption force between the microneedles and the gasket is less than 0.3 N, the microneedles are easily detached from the gasket, which is not conducive to the transportation or storage of the microneedles and the stability is poor. As can be seen from Table 2, after 6 months of storage of the microneedle patch prepared by the present invention, the adsorption force between the gasket and the microneedles is greater than 0.3 N, indicating that the microneedle patch of the present invention has good stability within the validity period, the bonding strength between the microneedles and the gasket is high, and it meets the requirements of long-term storage.

[0074] The microneedle patch after aging treatment was subjected to a microneedle film penetration test. It was found that the microneedle patch prepared in the embodiment of the present invention had a strong adsorption force between the microneedles and the gasket, and no microneedles fell off or broke when penetrating the film. The fixation effect could still be achieved after penetration and separation. Figure 1 As shown in FIG. 1 , the microneedle patch prepared in the comparative example has weak adsorption force on the microneedles and the gasket, and a large number of microneedles fall off and break when piercing the film, as shown in FIG. Figure 2 As shown, it is shown that the microneedle gasket of the present invention can achieve stable bonding of microneedles and still meet the usage strength requirements after being stored for a period of time.

[0075] [Examples 17-19, Comparative Examples 8-11]

[0076] According to Table 3, a soluble microneedle patch was prepared according to the following preparation method:

[0077] (1) filling a soluble microneedle solution (35 wt % dextran solution) into a microneedle mold to form a protruding droplet on the surface of the microneedle mold with a volume of 100 μg / cm2 and placing it at a humidity of 80% and a temperature of 15° C. for 30 min, and then placing it at a humidity of 60% and a temperature of 25° C. for 4 min for semi-drying;

[0078] (2) A TPU gasket (thickness 5 mm, elasticity 0.6 N, contact angle 35.376° after electron beam treatment, strength 7 kgy, speed 5 m / min) was bonded to the raised droplet to form an effective contact area for the gasket, and the mixture was dried at 25° C. at a humidity of 60% for 24 h, and demolded to obtain a soluble microneedle patch.

[0079] Table 3

[0080] Volume of raised droplet Pressure N Adsorption force between gasket and microneedle N Separation stability % Example 17 <![CDATA[πr 3 > 1 1.22 95.5 Example 18 <![CDATA[2 / 3π(r + d / 2) 3 > 5 2.16 100 Example 19 <![CDATA[1 / 3π(r + d / 2) 3 > 4 1.98 100 Comparative Example 8 <![CDATA[4 / 5πr 3 > 4 0.25 70.4 Comparative Example 9 <![CDATA[π(r + d / 2) 3 > 4 / 0 Comparative Example 10 <![CDATA[2 / 3π(r + d / 2) 3 > 0.5 1.04 85.6 Comparative Example 11 <![CDATA[2 / 3π(r + d / 2) 3 > 8 2.45 65.5

[0081] Note: r is the radius of the microneedle base on the surface of the microneedle mold, and d is the distance between the centers of adjacent microneedle bases on the surface of the microneedle mold.

[0082] It can be seen from Table 3 and Comparative Examples 8-9 that when the volume of the protruding droplets is too large, the solutions are prone to aggregate with each other and the microneedles will generate defective microneedles after drying. When the volume of the protruding droplets is too small, the droplets cannot effectively fill the microneedle base and cannot effectively form a backing with the gasket, thereby reducing the area of ​​the microneedle combined with the gasket, and therefore cannot be stably adsorbed to the gasket.

[0083] It can be seen from Comparative Examples 10-11 that when the pressing force when fitting the gasket is too small, a thicker base is easily formed, thereby reducing the effective bonding area between the microneedle and the gasket. When the pressing force is too large, it is easy to cause gaps or bubbles to appear on the microneedle base after drying, resulting in defective microneedles, thereby affecting the separation stability.

[0084] The above is a further description of the present invention in conjunction with specific embodiments, but these embodiments are merely exemplary and do not constitute any limitation to the scope of the present invention. Those skilled in the art should understand that the details and forms of the technical solutions of the present invention can be modified or replaced without departing from the spirit and scope of the present invention, but such modifications and replacements all fall within the protection scope of the present invention.

Claims

1. A spacer for a soluble microneedle patch, characterized in that, The contact angle of the gasket is 30 - 70°, and it is treated by electron irradiation. The electron irradiation treatment is as follows: the intensity is 7 - 14 kGy, and the treatment speed is 2 - 5 m / min.

2. The gasket according to claim 1, wherein, The contact angle of the gasket is 30 - 55°.

3. The gasket according to claim 1, wherein The contact angle of the gasket can be obtained by the following plasma treatment method: (a) The plasma power is 400 - 600 W, the distance between the plasma nozzle and the gasket is 2 - 8 mm, and the speed of the plasma nozzle is 30 - 80 mm / s, obtaining a contact angle of the gasket of 45 - 70°; (b) The plasma power is 600 - 800 W, the distance between the plasma nozzle and the TPU gasket is 3 - 12 mm, and the speed of the plasma nozzle is 60 - 150 mm / s, obtaining a contact angle of the gasket of 30 - 70°; (c) The plasma power is 800 - 1000 W, the distance between the plasma nozzle and the TPU gasket is 10 - 20 mm, and the speed of the plasma nozzle is 80 - 200 mm / s, obtaining a contact angle of the gasket of 30 - 70°.

4. The gasket according to claim 1, wherein, The elastic force of the gasket > 0.5 N, and the thickness of the gasket is 0.1 - 150 mm.

5. Use of the gasket according to any one of claims 1 - 4 in the preparation of a soluble microneedle patch.

6. A soluble microneedle patch, characterized in that, Containing the gasket according to any one of claims 1 - 4.

7. The soluble microneedle patch according to claim 6, wherein Comprising a gasket and soluble microneedles provided on the gasket.

8. A method for preparing a soluble microneedle patch containing the spacer according to any one of claims 6-7, characterized in that, Comprising the following steps: laminating the gasket with the microneedle substrate, drying, and demolding.

9. The preparation method according to claim 8, characterized in that, The sticky microneedle substrate has raised droplets, and the raised droplets are soluble microneedle solutions; The volume of the raised droplet is πr 3 -2 / 3π(r + d / 2) 3 , where r is the radius of the microneedle base on the surface of the microneedle mold, and d is the distance between the centers of adjacent microneedle bases on the surface of the microneedle mold.

10. The preparation method according to claim 9, characterized in that, Comprising the following steps: (1) Filling the soluble microneedle solution into a microneedle mold to form raised droplets, and performing semi - drying treatment; (2) Laminating the gasket onto the raised droplets under pressure, drying, and demolding; The semi - drying treatment in step (1) is: placing it at a humidity of 75% - 98% and a temperature not lower than 10°C for 10 min - 12 h, and then placing it at a humidity of 30% - 80% and a temperature of 20 - 45°C for 2 min - 60 min; The pressure of the lamination in step (2) is 1 - 5 N per square centimeter; The drying in step (2) is: drying at a humidity of 10% - 90% and a temperature of 20 - 30°C for 5 - 72 h.

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