Soluble microneedle patch and method of manufacturing the same

Abstract

The application discloses a soluble microneedle patch, comprising a microneedle part and a patch part. The microneedle part has a base and a plurality of microneedles, the base has a first surface and an opposite second surface, the microneedles are connected to the first surface, and the patch part is connected to the second surface. The microneedle part is made of a mixture, and the mixture comprises an excipient, the excipient comprises sodium alginate and dextrin, and the weight ratio of the dextrin to the sodium alginate is 0.2-1. In addition, a manufacturing method for manufacturing the soluble microneedle patch is also provided.

Description

TECHNICAL FIELD

[0001] The present application relates to a patch, in particular, a dissolvable microneedle patch with surface microneedles that can be dissolved and a manufacturing method thereof. BACKGROUND

[0002] A microneedle patch (MNP) is a transdermal drug delivery system (TDDS) that combines the advantages of both transdermal patches and subcutaneous injections. The microneedles are not long enough to stimulate the nerves of the skin, so the pain is relatively low. Because the microneedles can penetrate the stratum corneum on the surface of the skin, they can facilitate the delivery of large molecule drugs through the stratum corneum into the human body. It has been applied in the field of medical beauty.

[0003] Among them, the microneedle patch includes solid microneedles, coated microneedles, hollow microneedles, and dissolvable microneedles according to the types of microneedles on its surface. Among them, because the dissolvable microneedles do not have the risk of being left in the skin after the needle body breaks and cannot be absorbed, they are safer and have more development potential than other types of microneedles. SUMMARY

[0004] The present application provides a dissolvable microneedle patch with a smooth surface and is not easy to break, and does not have problems such as film surface curling, unevenness, or microneedle structure skewing or breaking.

[0005] The present application provides a manufacturing method for a dissolvable microneedle patch, and the manufactured microneedle patch has a smooth surface and is not easy to break, and does not have problems such as film surface curling, unevenness, or microneedle structure skewing or breaking.

[0006] To achieve the above advantages, an embodiment of the present application provides a dissolvable microneedle patch, comprising: a microneedle part and a patch part. The microneedle part has a base and a plurality of microneedles, the base has a first surface and an opposite second surface, and the microneedles are connected to the first surface; the patch part is connected to the second surface. The microneedle part is made of a mixture, and the mixture includes an excipient, wherein the excipient includes sodium alginate and dextrin, and the weight ratio of dextrin to sodium alginate is between 0.2 and 1.

[0007] In an embodiment of the present application, the height of the microneedle is 100-1500 µm.

[0008] In an embodiment of the present application, the shape of the microneedle is a pyramid or a cone.

[0009] In an embodiment of the present application, the mixture further includes a functional ingredient, and the functional ingredient is selected from the group consisting of hyaluronic acid, salicylic acid, vitamin C, nicotinic acid, vitamin B5, sulfur, gotu kola, vitamin E powder, ceramide, glycerol, GLP-1, insulin, acetaminophen, and combinations thereof.

[0010] The present application provides a manufacturing method of a dissolvable microneedle patch, comprising the following steps: providing a mold, a plurality of grooves are formed on the mold. A water solution is injected into the mold and the water solution is dried to form a microneedle substrate, the microneedle substrate comprises a plurality of microneedle parts, each microneedle part comprises a base and a plurality of microneedles, the shape of the microneedles corresponds to the shape of the grooves. A plurality of patch materials are attached to the microneedle parts. The microneedle substrate is cut to form a plurality of dissolvable microneedle patches. The water solution dissolves a mixture of excipients and functional ingredients, the excipients are composed of sodium alginate and dextrin, and the weight ratio of dextrin to sodium alginate is between 0.2 and 1.

[0011] In an embodiment of the present application, the water solution comprises 1.5% by weight of sodium alginate.

[0012] In an embodiment of the present application, the viscosity of the sodium alginate water solution is between 15 and 5000 cps.

[0013] In an embodiment of the present application, the drying condition of the water solution is drying at 30-60 degrees Celsius for 1-6 hours.

[0014] According to the above description, the dissolvable microneedle patch of the present application has the following advantages: because the weight ratio of sodium alginate and dextrin as excipients is adjusted, the surface of the base of the manufactured dissolvable microneedle part is flat and not easy to crack, and is suitable for beautiful attachment with the patch part. The manufactured dissolvable microneedle patch does not have problems such as film surface curling, unevenness, or microneedle structure skewing or breaking. The manufacturing method of the dissolvable microneedle patch of the present application has the advantages and characteristics of the above-mentioned dissolvable microneedle patch because the weight ratio of sodium alginate and dextrin as excipients is adjusted.

[0015] In order to make the above and other purposes, features and advantages of the present application more obvious and easy to understand, the following embodiments are described in detail below, and the accompanying drawings are described as follows. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 It is a side view of a dissolvable microneedle patch according to an embodiment of the present application.

[0017] Figures 2A to 2K It is a flowchart of a manufacturing method of a dissolvable microneedle patch according to an embodiment of the present application.

[0018] In the drawings, the reference signs are as follows:

[0019] 1: dissolvable microneedle patch

[0020] 11: microneedle part

[0021] 111: base

[0022] 111a: first surface

[0023] 111b: second surface

[0024] 112: microneedle

[0025] 12: patch portion

[0026] 121: back adhesive sheet

[0027] 121a: adhesive film

[0028] 13: release film

[0029] 131: hole

[0030] 14: combined film sheet

[0031] 3: mold

[0032] 3a: first mold

[0033] 31: microneedle area

[0034] 32: blank area

[0035] 3b: second mold

[0036] 31': groove

[0037] 4: aqueous solution of mixture

[0038] 41: microneedle substrate

[0039] 41a: remaining portion

[0040] 5: knife

[0041] H: height DETAILED DESCRIPTION

[0042] The present application will be described in detail by the following articles and specific examples, but not as a limitation of the present application.

[0043] In the following articles, the terms used in the description of the embodiments according to the present application, such as "upper", "lower", and the like, are indicative of the orientation or positional relationship described in the drawings shown, and the above terms are only for the convenience of describing the present application, and are not a limitation on the present application, i.e., not indicative or suggestive of the elements mentioned must have a particular orientation, constructed in a particular orientation. In addition, the terms "first", "second", etc. mentioned in the specification or the scope of the application are only used to name the elements or to distinguish different embodiments or ranges, and are not used to limit the upper or lower limit of the number of elements.

[0044] Figure 1FIG. 1 is a side view of a dissolvable microneedle patch according to an embodiment of the present application. FIG. 2 is a comparison chart of the test results of the component ratio of the microneedle portion. As shown in FIG. 1, the dissolvable microneedle patch 1 according to an embodiment of the present application includes a microneedle portion 11 and a patch portion 12. The microneedle portion 11 has a base 111 and a plurality of microneedles 112, the base 111 has a first surface 111a and an opposite second surface 111b, and the microneedles 112 are connected to the first surface 111a; the patch portion 12 is connected to the second surface 111b. The microneedle portion 11 is made of a mixture including an excipient, and the excipient includes sodium alginate and dextrin, and the weight ratio of the dextrin to the sodium alginate is between 0.2 and 1. Figure 1

[0045] In different embodiments of the present application, the mixture for making the microneedle portion 11 further includes a functional component in addition to the excipient. The functional component is, for example, a component that does not affect the film formation of the microneedle portion 11 during the manufacturing process, and the functional component is, for example, but not limited to, hyaluronic acid, salicylic acid, vitamin C, nicotinic acid, vitamin B5, sulfur, gotu kola, vitamin E powder, ceramide, glycerol, GLP-1, insulin, acetaminophen, and combinations of components for medical or cosmetic purposes, which can be selected according to the actual product requirements.

[0046] In different embodiments of the present application, the height H of the microneedle 112 made of the mixture of sodium alginate and dextrin having the above component ratio is between 100 and 1500 µm, and the microneedle 112 has good mechanical properties and is not easy to break during use. The shape of the microneedle 112 is, for example, a pyramid or a cone, which can be changed according to requirements (see the manufacturing method described later).

[0047] As shown in FIG. 1, in this embodiment, the patch portion 12 includes, for example, an adhesive sheet 121 and a release film 13. One side surface of the adhesive sheet 121 is provided with an adhesive film 121a, and a part of the surface of the adhesive film 121a is adhered to the bottom of the microneedle portion 11, and another part of the surface of the adhesive film 121a is adhered to the release film 13. The adhesive sheet 121 is not separated from the base 111 of the microneedle portion 11 by the adhesive film 121a, and is also adhered to the skin of the user by the adhesive film 121a. The release film 13 is suitable for covering a part of the adhesive film 121a to maintain the cleanliness of the adhesive film 121a and keep the adhesion of the adhesive film 121a, and the release film 13 should be peeled off during use. Figure 1

[0048] Specifically, the adhesive sheet 121 is, for example, a film sheet of polyurethane (PU), and the release film 13 is, for example, a polyethylene terephthalate (PET) release film, but the materials are not limited thereto, and the adhesive film 121a can be made of a material suitable for being attached to the human body, for example.

[0049] ​​In actual use of the dissolvable microneedle patch 1, for example, the release film 13 connected to the back adhesive film 121 is removed to expose a portion of the adhesive film 121a, and then the entire microneedle 112 patch is covered on the skin of the user, so that the microneedles 112 of the microneedle part 11 are pierced into the skin, and the dissolvable microneedle patch 1 is adhered to the skin through the adhesive film 121a of the back adhesive film 121.

[0050] Table 1 is a schematic diagram of the test results of adjusting the composition ratio of sodium alginate and dextrin in the microneedle part 11.

[0051] (Table 1)

[0052] No Ingredient 1 (wt%) Ingredient 2 (wt%) Ingredient 2 / 1 wt ratio Film surface flatness Film separation Evaluation result No. 1 Sodium alginate 1% Dextrin 0% 0 Crinkled Not broken NG No. 2 Sodium alginate 1.5% Dextrin 0% 0 Crinkled Not broken NG No. 3 Sodium alginate 2.0% Dextrin 0% 0 Crinkled Not broken NG No. 4 Sodium alginate 1.5% Dextrin 0% 0 Slightly crinkled Not broken NG No. 5 Sodium alginate 1.5% Dextrin 0.2% 0.13 Flat Not broken OK No. 6 Sodium alginate 1.5% Dextrin 0.3% 0.2 Flat Not broken OK No. 7 Sodium alginate 1.5% Dextrin 0.4% 0.27 Flat Not broken OK No. 8 Sodium alginate 1.5% Dextrin 0.5% 0.33 Flat Not broken OK No. 9 Sodium alginate 1.5% Dextrin 0.75% 0.5 Flat Not broken OK No. 10 Sodium alginate 1.5% Dextrin 0.9% 0.6 Flat Not broken OK No. 11 Sodium alginate 1.5% Dextrin 1% 0.67 Flat Not broken OK No. 12 Sodium alginate 1.5% Dextrin 1.5% 1 Flat Not broken OK No. 13 Sodium alginate 1.5% Dextrin 1.75% 1.16 Flat Broken NG No. 14 Sodium alginate 1.5% Dextrin 2% 1.33 Flat Broken NG

[0053] Referring to (Table 1), in order to find the suitable ratio of the excipient components in the mixture for making the microneedle part 11, referring to the tests of No. 1 to No. 4 in (Table 1), in the aqueous solution for making the microneedle part 11, the example of using sodium alginate as the excipient, after the experiment, it is known that when only sodium alginate is used as the excipient, regardless of the ratio of sodium alginate, although the finished product (microneedle substrate 41, see the subsequent manufacturing method) produced will not be broken when it is removed from the mold (see Table 1, release film property), but the surface will be curled and not suitable for production (see Table 1, film surface flatness).

[0054] Referring to the test of No. 5 in (Table 1), in the aqueous solution for making the microneedle part 11, the example of using a mixture containing only 1.5% by weight of sodium alginate and 0.2% by weight of dextrin as the excipient, from the table, it is known that the finished product produced will not be broken when it is removed from the mold (see Table 1, release film property), and the degree of curling is improved, but there is still a slight curling (see Table 1, film surface flatness), which is not suitable for use as the microneedle part 11 of the product.

[0055] Referring to the tests of No. 6 to No. 12 in (Table 1), in the aqueous solution for making the microneedle part 11, the example of using a mixture containing only 1.5% by weight of sodium alginate and 0.3%, 0.4%, 0.5%, 0.75%, 0.9%, 1%, and 1.5% by weight of dextrin, respectively, as the excipient, after the experiment, it is known that the finished product produced will not be broken when it is removed from the mold (see Table 1, release film property), and the film surface is flat (see Table 1, film surface flatness), which is suitable for use as the microneedle part 11 of the product.

[0056] Please refer to the tests No. 13 to No. 14 in Table 1. In the example of using a mixture of sodium alginate at a weight ratio of only 1.5% and dextrin at weight percentages of 1.75% and 2% respectively as excipients in the aqueous solution for making microneedle part 11, it can be seen from the experiment that although the finished product has a smooth film surface (see Table 1, film surface smoothness), it is easy to break when it is removed from the mold (see Table 1, film release property), and is not suitable for use as microneedle part 11 of the product.

[0057] Figures 2A to 2K This is a schematic flowchart illustrating a method for manufacturing a soluble microneedle patch 1 according to an embodiment of the present invention. Figure 2A As shown, the manufacturing method of the aforementioned soluble microneedle patch 1 includes the following steps in one embodiment: providing a mold 3, on which a plurality of grooves 31' are formed (see...). Figure 2C ). Inject aqueous solution 4 into mold 3 (see Figure 2D The aqueous solution 4 is, for example, an aqueous solution containing the mixture used in the aforementioned soluble microneedle patch 1. The aqueous solution 4 is dried to form a microneedle substrate 41, which includes a plurality of microneedle portions 11, each microneedle portion 11 including a base 111 and a plurality of microneedles 112 (see...). Figure 1 The shape of the microneedle 112 corresponds to the shape of the groove 31' (see...). Figures 2D to 2F Multiple patch materials are adhered to the microneedle portion 11 (see...). Figures 2G to 2H Cut the microneedle substrate 41 to form multiple soluble microneedle patches 1 (see...). Figures 2J to 2K ).

[0058] For details, please refer to Figure 2A As shown, a first mold 3a is first made. The material of the first mold 3a can be metal. It has microneedles (unlabeled) with shapes and sizes corresponding to the microneedles 112 to be formed. The first mold 3a forms multiple microneedle areas 31 and blank areas 32 located between the microneedle areas 31 according to the distribution position of the microneedles. The range of the microneedle area 31 is set according to the range of the microneedle part 11 on the soluble microneedle patch 1.

[0059] like Figure 2B As shown, a second mold 3b with a shape corresponding to the first mold 3a is made using the first mold 3a, and the first mold 3a and the second mold 3b are then separated (e.g., Figure 2CThe second mold 3b has grooves 31' corresponding to the microneedles on the first mold 3a. In this embodiment, the periphery of the second mold 3b is formed with a border protruding from its surface (not shown), thereby allowing the aqueous solution 4 to be stored in the center of the second mold 3b through the border. The material of the second mold 3b is, for example, polydimethylsiloxane (PDMS), but is not limited thereto. The second mold 3b will be used as the mold 3 for fabricating the microneedle portion 11 of the soluble microneedle patch 1.

[0060] like Figure 2D As shown, when fabricating the microneedle 11, an aqueous solution 4 is first injected into the mold 3. As described in the preceding paragraph, the aqueous solution 4 contains excipients and functional components. The excipients include sodium alginate and dextrin, with a weight ratio of dextrin to sodium alginate between 0.2 and 1. The viscosity of the aqueous solution 4 (which can be considered as a sodium alginate aqueous solution) is, for example, between 15 and 5000 cps. The viscosity can be determined by adjusting the molecular weight of sodium alginate.

[0061] like Figure 2E As shown, degassing is performed after injecting the aqueous solution 4 to prevent air bubbles from remaining in the groove 31' due to the viscosity of the aqueous solution 4, which would cause incomplete shapes in the subsequently fabricated microneedles 112. Degassing can be performed, for example, by vacuum degassing at room temperature, but is not limited to this method.

[0062] Next, as Figure 2F As shown, the aqueous solution 4 is dried to solidify it and form the microneedle substrate 41. The drying conditions for the aqueous solution 4 are, for example, drying at 30-60 degrees Celsius for 1-6 hours, which can be selected according to actual needs.

[0063] like Figure 2G As shown, while the microneedle substrate 41 remains in the mold 3, a patch material is applied to the microneedle substrate 41. The patch material is, for example, a material having multiple adhesive backing sheets 121 (for ease of representation, denoted as 121). Figures 2G to 2K The composite film 14 is composed of an adhesive backing sheet 121 (drawn as patch portion 12) and a release film 13. The release film 13 has multiple holes 131. Each adhesive backing sheet 121 covers one hole 131. The adhesive backing sheet 121 is bonded to the release film 13 through an adhesive film 121a, and each adhesive backing sheet 121 covers the same side surface of the release film 13. Therefore, when the composite film 14 is bonded to the microneedle substrate 41, each adhesive backing sheet 121 and the microneedle substrate 41 are located on opposite sides of the release film 13. The size and position of the holes 131 on the release film 13 correspond to the size and position of the base 111 of the manufactured soluble microneedle patch 1.

[0064] like Figure 2G and Figure 2HAs shown, then, the combined film sheet 14 is pressed so that the adhesive sheet 121 on the patch material is bonded to the microneedle substrate 41. Here, the microneedle substrate 41 forms the microneedle portion 11 at the portion where the holes 131 are present, and forms the remaining portion 41a at the portion other than the microneedle portion 11. Then, as shown Figure 2I As shown, the combination of the combined film sheet 14 and the microneedle substrate 41 is detached from the mold 3.

[0065] As shown Figure 2J and Figure 2K As shown, then, the remaining portion 41a is separated from the microneedle portion 11 by, for example, a cutter 5, and the remaining portion 41a is removed, thereby forming the dissolvable microneedle patch 1 on the release film 13. The actual type of the cutter 5 can be selected as needed, and can be, for example, a physical cutter or a laser. As shown Figure 2K As shown, by the above method, a plurality of dissolvable microneedle patches 1 can be simultaneously produced on one release film 13, and the dissolvable microneedle patches 1 are connected to each other by the release film 13. In other embodiments, in the step of cutting the remaining portion 41a, the release film 13 can also be cut so as to produce a plurality of dissolvable microneedle patches 1 that are separated from each other. The cutting method can be determined as needed for product packaging, and is not limited thereto.

[0066] As described above, the dissolvable microneedle patch of the present application, because the weight ratio of sodium alginate and dextrin as excipients is adjusted, the surface of the base of the produced dissolvable microneedle portion is flat and not easily broken, and is suitable for beautiful attachment to the patch portion. The produced microneedle patch does not have problems such as curling of the film surface, unevenness, or tilting or breaking of the microneedle structure. The manufacturing method of the dissolvable microneedle patch of the present application, because the weight ratio of sodium alginate and dextrin as excipients is adjusted, the produced microneedle patch has the advantages and features of the above-described dissolvable microneedle patch.

[0067] Although the present application has been disclosed with reference to the embodiments above, it is not intended to limit the present application, and those having ordinary knowledge in the technical field to which the present application pertains can make some changes and modifications without departing from the spirit and scope of the present application. Therefore, the scope of the present application is defined by the appended claims.

Claims

1. A dissolvable microneedle patch, characterized by, Comprising: a microneedle part having a base and a plurality of microneedles, the base having a first surface and an opposite second surface, the microneedles connected to the first surface; and a patch part connected to the second surface; wherein the microneedle part is made of a mixture comprising an excipient, wherein the excipient consists of sodium alginate and dextrin, the weight ratio of the dextrin to the sodium alginate being between 0.2 and 1. The height of the microneedles is between 100 and 1500 µm.

2. The dissolvable microneedle patch of claim 1, wherein, The shape of the microneedles is pyramidal or conical.

3. The dissolvable microneedle patch of claim 1, wherein, The mixture further comprises a functional ingredient selected from one or more of hyaluronic acid, salicylic acid, vitamin C, niacin, vitamin B5, sulfur, gotu kola, vitamin E powder, ceramide, glycerin, GLP-1, insulin, acetaminophen.

4. The dissolvable microneedle patch of claim 1, wherein, Comprising:

5. A method of manufacturing a dissolvable microneedle patch, characterized by, providing a mold having a plurality of recesses formed thereon; injecting an aqueous solution into the mold; drying the aqueous solution to form a microneedle substrate comprising a plurality of microneedle parts, each of the microneedle parts comprising a base and a plurality of microneedles, the shape of the microneedles corresponding to the shape of the recesses; attaching a plurality of patch materials to the microneedle parts; and cutting the microneedle substrate to form a plurality of dissolvable microneedle patches; wherein the aqueous solution dissolves a mixture of an excipient and a functional ingredient, the excipient consisting of sodium alginate and dextrin, the weight ratio of the dextrin to the sodium alginate being between 0.2 and 1. The aqueous solution comprises 1.5% by weight of sodium alginate.

6. The method of claim 5, wherein the dissolvable microneedle patch is manufactured by the steps of: The viscosity of the sodium alginate is between 15 and 5000 cps.

7. The method of claim 6, wherein the dissolvable microneedle patch is manufactured by the steps of: The condition for drying the aqueous solution is drying at 30-60 degrees Celsius for 1-6 hours.

8. The method for manufacturing the soluble microneedle patch as described in claim 5, characterized in that, ​

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