Water-permeable microneedle patch

Abstract

The present disclosure provides a water permeable microneedle patch comprising a base material, a bonding layer, a back layer and a microneedle region, a plurality of microneedles are disposed in the microneedle region, the microneedles are disposed on the back layer, the water permeable microneedle patch further comprises a hollow portion, the hollow portion comprises at least one hollow channel, and the hollow channel is disposed in the hollow portion. The hollow-out channel is formed in the base material and the bonding layer in a penetrating mode and is adjacent to the back layer, the microneedles are arranged above the hollow-out part, and the volume of the hollow-out part is larger than or equal to 10 volume percent and smaller than or equal to 50 volume percent relative to the total volume of the base material and the bonding layer. Therefore, the permeable microneedle patch disclosed by the invention can maintain good mechanical strength, improve the dissolution rate of the microneedle, shorten the service time, and achieve the effects of improving the use convenience and reducing the risk.

Description

Technical Field

[0001] The present disclosure relates to a microneedle patch, in particular to a fast-dissolving microneedle patch. Background Art

[0002] Transdermal drug delivery has gained significant attention in recent years. It allows active substances (such as drugs or vaccines) to be absorbed through the skin and exert their efficacy through non-invasive delivery methods. However, due to the hydrophobic and negatively charged nature of the skin's stratum corneum, it is not suitable for the delivery of water-soluble drugs or vaccines via traditional transdermal drug delivery systems.

[0003] In view of this, the existing technology has developed a microneedle patch, which has a substrate covered with multiple micron-level microneedles. These microneedles can pierce the stratum corneum of the skin and deliver active substances such as drugs or vaccines to the epidermis for dissolution and release. The microneedle patch can expand the types of active substances to be delivered to the water-soluble category, so that various types of active substances can be directly delivered to the epidermis or dermis through the microneedles on the microneedle patch to release the drug effect without causing pain. Based on the many advantages of microneedle patches, in addition to their application in the fields of medicine and vaccines, their application in medical beauty-related fields such as skin beauty has gradually expanded.

[0004] Specifically, Figure 9 The structure of the microneedle patch in the prior art includes, from bottom to top, a substrate 11, an adhesive layer 12, a backing layer 13, and a microneedle area 14. The microneedle area 14 is provided with a plurality of microneedles 141. The microneedles 141 are provided on the backing layer 13. The substrate 11 and the adhesive layer 12 are used to support the backing layer 13 and the microneedles 141 in the microneedle area 14, so that the microneedles 141 can pierce the stratum corneum of the skin without breaking, thereby achieving the effect of delivering active substances.

[0005] However, when using microneedle patches, since the microneedles remain embedded in the skin, prolonged use can lead to adverse effects. For example, prolonged waiting can affect the convenience of use, restricting the user's movements while waiting to maintain the adhesion of the microneedle patch. Prolonged adhesion can also cause skin discomfort, irritation, and allergic reactions, reducing acceptance. Furthermore, since some medications or beauty products can lose their activity after prolonged contact with air and skin, prolonged use can also reduce their effectiveness. Furthermore, it can increase the risk of infection. Since microneedles form tiny channels in the skin, prolonged use increases the chances of bacteria or other microorganisms entering the body.

[0006] Therefore, there is still a need to develop and research a microneedle patch with a faster microneedle dissolution rate, which can shorten the use time of the microneedle patch, improve user convenience and acceptance, and reduce concerns about the risk of derivative infection. Summary of the Invention

[0007] In view of the above technical problems, the purpose of the present disclosure is to provide a water-permeable microneedle patch, which helps to quickly dissolve the microneedles of the microneedle patch, thereby shortening the usage time.

[0008] In order to achieve the aforementioned objectives, the present disclosure provides a water-permeable microneedle patch, which includes a substrate, an adhesive layer, a backing layer and a microneedle area, and a plurality of microneedles are arranged in the microneedle area, and the microneedles are arranged on the backing layer. The water-permeable microneedle patch also includes a hollow portion, the hollow portion includes at least one hollow channel, the hollow channel is formed through the substrate and the adhesive layer and is adjacent to the backing layer, the microneedles are arranged above the hollow portion, and the volume of the hollow portion relative to the total volume of the substrate and the adhesive layer is greater than or equal to 10 volume percent (v / v%) and less than or equal to 50 v / v%.

[0009] Through the structural setting of the hollow part, the active substance applied to the water-permeable microneedle patch of the present invention can act on the back layer and multiple microneedles along the hollow channel, accelerate the dissolution rate of the multiple microneedles, and thus shorten the usage time, thereby achieving the effect of improving the convenience of use and reducing the risk; at the same time, by controlling the volume percentage of the hollow part relative to the substrate and the adhesive layer (hereinafter referred to as the volume ratio of the hollow part), the water-permeable microneedle patch of the present invention can also maintain good mechanical strength to ensure that the multiple microneedles can pierce the stratum corneum of the skin without breaking, so that the active substance can be transported to the epidermis for dissolution and release.

[0010] Preferably, the volume proportion of the hollow portion may be 20 v / v% to 50 v / v%, more preferably 30 v / v% to 50 v / v%, and even more preferably 40 v / v% to 50 v / v%. In one embodiment, the volume proportion of the hollow portion may be 15 v / v%, 20 v / v%, 25 v / v%, 30 v / v%, 35 v / v%, 40 v / v%, 45 v / v%, or 50 v / v%. The volume proportion of the hollow portion may be within a range formed by any two of the aforementioned values, but is not limited thereto.

[0011] Preferably, the microneedles may be arranged above the hollow channel.

[0012] According to the present disclosure, the backing layer has an upper surface and a lower surface opposite to each other, the lower surface of the backing layer is bonded to the bonding layer, and the microneedles are formed on the upper surface of the backing layer.

[0013] According to the present disclosure, there may be one or more hollow channels, and the cross-sectional area of ​​these hollow channels is 11% to 50% relative to the area of ​​the microneedle area (i.e., the overlapping area of ​​the microneedle area with multiple microneedles and the back layer).

[0014] According to the present disclosure, the substrate is made of a waterproof material, which may be a polyethylene film, a polyethylene terephthalate (PET) film, a thermoplastic polyurethane (TPU) film, or a combination thereof, but is not limited thereto.

[0015] According to the present disclosure, the water-permeable microneedle patch further includes a release layer, which is disposed on the adhesive layer and located next to the backing layer.

[0016] According to the present disclosure, the covering layer is a water-permeable material. For example, the covering layer can be a facial mask cloth, medical gauze or water needle cloth, but is not limited thereto. In certain embodiments of the present disclosure, the covering layer is located on the side of the substrate relative to the adhesive layer. Preferably, the water-permeable microneedle patch of the present disclosure further comprises an adhesive layer, which is located between the covering layer and the substrate, so that the covering layer and the substrate can be more tightly superimposed. Specifically, the adhesive layer is located below the release layer, that is, not below the microneedle area. In this way, the setting of the adhesive layer will not hinder the interaction between the hollow channel and the back layer and the plurality of microneedles, thereby affecting the dissolution rate of the microneedles.

[0017] According to the present disclosure, the backing layer may include polyvinylpyrrolidone / vinyl acetate (PVP / VA), high-viscosity hydroxypropylmethylcellulose (HPMC, with a viscosity of 4000 centipoise (cP)), low-viscosity hydroxypropylmethylcellulose (with a viscosity of 4.5 cP), pentylene glycol, a silicone defoamer, and 4-hydroxyacetophenone, but is not limited thereto. Specifically, relative to the composition weight of the entire backing layer, the content of vinyl pyrrolidone-vinyl acetate copolymer is 1.0 weight percent (wt%) to 2.0 wt%, the content of high-viscosity hydroxypropyl methylcellulose is 0.5 wt% to 1.0 wt%, the content of low-viscosity hydroxypropyl methylcellulose is 0.3 wt% to 0.6 wt%, the content of pentylene glycol is 0.3 wt% to 0.6 wt%, the content of silicone defoaming agent is 0.01 wt% to 0.05 wt%, and the content of parahydroxyacetophenone is 0.1 wt% to 0.4 wt%.

[0018] In certain embodiments of the present disclosure, the composition of the backing layer can be further controlled so that the backing layer can be quickly dissolved, and effective ingredients can be added thereto to achieve preventive health care, promoting repair, moisturizing, anti-inflammatory, soothing and other effects, but not limited to these. Specifically, the moisturizing ingredients that can be used in the present invention include, but are not limited to, ceramide, lecithin, glycerol, polysaccharides, hyaluronic acid, sodium hyaluronate, protein, collagen, elastin, peptides, amino acids, citrate, uric acid, urea, glucose, sucrose, fructose, glycogen, glucosamine, mucopolysaccharides, lactate, phosphate, and ethyl-di-2-pyrrolidone-5-carboxylate.The anti-inflammatory or soothing ingredients that can be used in the present invention include: grape extract, green tea extract, ginkgo extract, soy extract, pomegranate extract, ginger extract, yeast extract, coix extract, lipoic acid (R-alpha-lipoic acid), glucan, coenzyme Q10 (coenzyme Q10), superoxide dismutase (SOD), vitamin C and its derivatives, vitamin E and its derivatives, topical anti-inflammation agents, steroidal anti-inflammatory materials, non-steroidal anti-inflammatory materials, anti-pain and anti-inflammation ingredients. material) and analogs, vitamin B and its derivatives, licorice extract, pentacyclic triterpenoid saponins (triterpenoids), madecassoside, asiaticoside, mucosa coating, glutathione, lycopene, but are not limited to these.

[0019] Preferably, the backing layer may also contain an antimicrobial agent. Specifically, the antimicrobial agents include p-hydroxyacetophenone, pentylene glycol, hexanediol, caprylyl glycol, phenoxyethanol, benzyl alcohol, salicylic acid, benzoic acid, sorbic acid, potassium sorbate, propionic acid, dehydroacetic acid, chlorophenesin, behentrimonium chloride, benzalkonium chloride, benzethonium chloride, butylbenzoate, dimethyl oxazolidine, bromochlorophene, dichlorobenzyl alcohol, ethyl lauroyl arginate HCl, HCl), 7-ethylbicyclooxazolidine, formic acid, glutaral, hexamidine, sodium sulfite, iodopropynyl butylcarbamate, methylisothiazolinone, butylparaben, methylparaben, phenoxyisopropanol, phenylmercuric acetate, triclocarban, undecylenic acid, zinc pyrithione, 5-bromo-5-nitro-1,3-dioxane3-dioxane), benzylhemiformal, DMDM ​​Hydantoin, diazolidinyl urea, imidazolidinyl urea, methenamine, quaternium-15, sodium hydroxymethylglycinate, Leuconostoc, Lactobacillus ferment, Populus Tremuloides Bark Extract, Black Currant Fruit Extract, or a combination thereof, but are not limited thereto. More preferably, the antibacterial agent comprises a lactobacillus ferment, methylisothiazolinone, or a combination thereof.

[0020] In one embodiment of the present disclosure, to enable rapid dissolution of the backing layer, the backing layer may include less than 0.1 wt% of high-viscosity hydroxypropyl methylcellulose relative to the weight of the entire backing layer, or may be substantially free of high-viscosity hydroxypropyl methylcellulose. Specifically, the backing layer may include vinyl pyrrolidone-vinyl acetate, low-viscosity hydroxypropyl methylcellulose, sodium hyaluronate, dipotassium glycyrrhizinate (DPG) from licorice extract, lactobacillus fermentation products, and methylisothiazolinone, but is not limited thereto. Relative to the composition weight of the entire back layer, the content of vinyl pyrrolidone-vinyl acetate copolymer is 1.0wt% to 2.0wt%, the content of low-viscosity hydroxypropyl methylcellulose is 0.2wt% to 0.5wt%, the content of sodium hyaluronate is 0.5wt% to 2.0wt%, the content of dipotassium glycyrrhizate is 0.05wt% to 0.5wt%, the content of lactobacillus fermentation product is 0.5wt% to 1.0wt%, and the content of methylisothiazolinone is 0.05wt% to 0.1wt%.

[0021] According to the present disclosure, the composition of these microneedles may include hyaluronic acid, pentanediol, and parahydroxyacetophenone, but is not limited thereto. Specifically, the hyaluronic acid may include macromolecular hyaluronic acid, small molecule hyaluronic acid, modified hyaluronic acid, and cross-linked hyaluronic acid, but is not limited thereto, wherein the molecular weight of the small molecule hyaluronic acid is less than 2 kilodaltons (kDa), and the molecular weight of the macromolecular hyaluronic acid is 50kDa to 100kDa. For example, the modified hyaluronic acid may be amino acid-modified hyaluronic acid or histidine-modified hyaluronic acid, but is not limited thereto; the cross-linked hyaluronic acid is prepared by cross-linking hyaluronic acid with a cross-linking agent, and the cross-linking agent may be 1,4-butanediol diglycidyl ether (BDDE), divinyl sulfone (DVS), adipic acid dihydrazide (ADD), or the like. dihydrazide, ADH), carbodiimide (also known as 1-ethyl-(3-dimethylaminopropyl)carbodiimide (1-ehtyl-3-(3-dimethylaminopropyl)carbodiimide, EDC), glycidyl methacrylate (glycidylmethacylate, GMA), but not limited thereto. Specifically, relative to the weight of the overall microneedle composition, the content of the hyaluronic acid is 5wt% to 7wt%, the content of the pentylene glycol is 0.3wt% to 0.7wt%, and the content of the p-hydroxyacetophenone is 0.1wt% to 0.4wt%.

[0022] According to the present disclosure, the mechanical strength of the microneedles is greater than 0.058 Newtons per needle (N / needle). This mechanical strength is sufficient to ensure that the microneedles can penetrate the stratum corneum of the skin without breaking, allowing active substances such as skincare solutions or drugs to be delivered to the epidermis for dissolution and release. Preferably, the mechanical strength of the microneedles is greater than 0.08 N / needle. More preferably, the mechanical strength of the microneedles is greater than 0.1 N / needle.

[0023] In some embodiments of the present disclosure, the area of ​​the microneedle region may be 3 square centimeters to 5 square centimeters.

[0024] In some embodiments of the present disclosure, the height of the microneedles is greater than or equal to 290 micrometers (μm) and less than or equal to 310 μm.

[0025] According to the present disclosure, the microneedles may be in the shape of a cone, a square cone, or a spire, but are not limited thereto.

[0026] According to the present disclosure, the density of the microneedles may be between 1 needle / cm 2 ) to 500 needles / cm 2; preferably 1 needle / cm 2 Up to 200 needles / cm 2 .

[0027] In this specification, the range represented by "a small value to a large value" means that the range is greater than or equal to the small value and less than or equal to the large value, unless otherwise specified. For example, the density of microneedles can be between 1 needle / cm 2 Up to 500 needles / cm 2 , which means that the density range of microneedles is "greater than or equal to 1 needle / cm 2 And less than or equal to 500 needles / cm 2 ”. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1A is a side cross-sectional view of the water-permeable microneedle patch of Example 1;

[0029] Figure 1B is a top view of the water-permeable microneedle patch of Example 1;

[0030] Figure 2 is a top view of the water-permeable microneedle patch of Example 2;

[0031] Figure 3 is a top view of the water-permeable microneedle patch of Example 3;

[0032] Figure 4 is a side cross-sectional view of the water-permeable microneedle patch of Example 4;

[0033] Figure 5 1 is a graph showing the mechanical strength test of the water-permeable microneedle patches of Examples 1, 2, and 3;

[0034] Figure 6A is a top view of the water-permeable microneedle patch of Example 2 before use;

[0035] Figure 6B is a top view of the microneedle patch of Comparative Example 1 after 15 minutes of use;

[0036] Figure 6C is a top view of the water-permeable microneedle patch of Example 2 after 15 minutes of use;

[0037] Figure 6D is a top view of the water-permeable microneedle patch of Example 5 after 15 minutes of use;

[0038] Figure 7A 3 is a side view of the microneedles of the water-permeable microneedle patch of Example 2 before use;

[0039] Figure 7BThis is a side view of the microneedles of the microneedle patch of Comparative Example 1 after 15 minutes of use;

[0040] Figure 7C This is a side view of the microneedles of the water-permeable microneedle patch of Example 5 after 15 minutes of use;

[0041] Figure 7D This is a side view of the microneedles of the water-permeable microneedle patch of Example 7 after 15 minutes of use;

[0042] Figure 8A is a photograph of the skin surface of a subject 15 minutes after application of the water-permeable microneedle patch of Example 5;

[0043] Figure 8B is a photograph of the skin surface of a subject 15 minutes after application of the water-permeable microneedle patch of Example 7;

[0044] Figure 9 This is a side cross-sectional view of the microneedle patch of Comparative Example 1. DETAILED DESCRIPTION

[0045] Several manufacturing methods of the embodiments are listed below as examples to illustrate the implementation methods of the present disclosure. Those skilled in the art can easily understand the advantages and effects that can be achieved by the present disclosure through the contents of this specification, and make various modifications and changes without departing from the spirit of the present disclosure to implement or apply the contents of the present disclosure.

[0046] Description of main reagents

[0047] 1. Small molecule hyaluronic acid: purchased from Kewpie, Japan; average molecular weight is about 2 kDa; and when dissolved in water at 1 wt%, its pH value is 5.0 to 7.0 at 25°C and a shear rate of 1 s -1 The viscosity measured below is less than 2 cP.

[0048] 2. Histidine-modified hyaluronic acid: purchased from the Industrial Technology Research Institute; when dissolved in water at 1 wt % content, its pH value is 5.0 to 7.0, at 25°C and a shear rate of 1s -1 The viscosity measured below is 4 cP to 5 cP.

[0049] 3. Cross-linked hyaluronic acid: purchased from the Industrial Technology Research Institute, using 1,4-butanediol diglycidyl ether as a cross-linker; solid content of approximately 4.5 wt%; pH value of 5.0 to 7.5; at 25°C and a shear rate of 1 s -1 The viscosity measured below is approximately 5000 cP to 8000 cP.

[0050] 4. Pentanediol: purchased from ACTIVON.

[0051] 5. p-Hydroxyacetophenone: purchased from Symrise.

[0052] 6. High viscosity hydroxypropyl methylcellulose: purchased from Shinetsu Chemical Industry Co., Ltd., product model 60SH-4000; after dissolving in water at a content of 2 wt%, at 20 ° C and a shear rate of 1s -1 The viscosity measured below is approximately 3000 cP to 5000 cP.

[0053] 7. Low viscosity hydroxypropyl methylcellulose: purchased from Shin-Etsu Chemical Industry Co., Ltd., product model PHARMACOAT 645; after dissolving in water at a content of 2 wt%, at 20 ° C and a shear rate of 1 s -1 The viscosity measured below is approximately 3.6 cP to 5.1 cP.

[0054] 8. Vinyl pyrrolidone-vinyl acetate copolymer: purchased from BASF.

[0055] 9. Lactobacillus fermentation product: purchased from ACTIVE MICRO, product model SF Max.

[0056] 10. Macromolecular hyaluronic acid: purchased from Zhongshan Biotechnology Co., Ltd.; the product model is Sodium Hyaluronate; its molecular weight is 50kDa to 100kDa.

[0057] 11. Silicone defoamer: purchased from Dow Corning, product model is DOWSIL TM 62Additive.

[0058] Example 1: Water-permeable microneedle patch

[0059] like Figure 1A and Figure 1BAs shown, the water-permeable microneedle patch 10 of Example 1 comprises, from bottom to top, a substrate 11, a bonding layer 12, a backing layer 13, and a microneedle area 14, and a plurality of microneedles 141 are provided in the microneedle area 14, and the microneedles 141 are provided on the backing layer 13. The water-permeable microneedle patch 10 further comprises a hollow portion, which comprises a plurality of hollow channels 15, each hollow channel 15 is formed through the substrate 11 and the bonding layer 12 and is adjacent to the backing layer 13, that is, the backing layer 13 covers one end of each hollow channel 15, and the microneedles 141 are provided above the hollow portion, and the volume of the hollow portion (that is, the total volume of the hollow channels 15) accounts for 11.58 v / v%. Specifically, the back layer 13 is formed between the adhesive layer 12 and the microneedle area 14. The back layer 13 has an upper surface and a lower surface relative to each other. The lower surface of the back layer 13 is bonded to the adhesive layer 12, and the microneedles 141 are formed on the upper surface of the back layer 13. The microneedles 141 can be arranged above each hollow channel 15.

[0060] In this embodiment, the water-permeable microneedle patch 10 further includes a release layer 16 , which is disposed on the adhesive layer 12 and located next to the backing layer 13 .

[0061] In this embodiment, the water-permeable microneedle patch 10 further includes a covering layer 17 , which is disposed on a side of the substrate 11 opposite to the adhesive layer 12 .

[0062] Through the structural setting of the hollow portion, the active substance applied to the water-permeable microneedle patch 10 will react with the back layer 13 and the microneedles 141 along the hollow channels 15, thereby increasing the dissolution rate of the microneedles 141, thereby shortening the usage time, thereby achieving the effect of improving convenience of use and reducing risks; at the same time, by controlling the volume ratio of the hollow portion, the water-permeable microneedle patch 10 can maintain good mechanical strength to ensure that the microneedles 141 can pierce the stratum corneum of the skin without breaking, so that the active substance can be transported to the epidermis for dissolution and release.

[0063] During the production process, the water-permeable microneedle patch 10 of the present disclosure can be prepared by the following method.

[0064] First, a master mold with a reference surface and multiple holes is selected. Each hole is recessed downward from the reference surface, and multiple holes are arranged in a matrix on the master mold. The master mold is made of polydimethylsiloxane (PDMS) and has a hole density of 110.6 holes / cm2 (holes / cm 2 ), the hole array area is about 3.65 square centimeters (cm 2), the shape of each hole is square cone, its depth (i.e. the vertical distance between the tip of the hole and the master mold reference plane) is about 290μm to 310μm, the maximum width (i.e. the maximum inner diameter of the horizontal plane of the hole flush with the master mold reference plane) is about 130μm to 170μm, and the number of needles in the entire hole array range is 400.

[0065] Next, appropriate amounts of modified hyaluronic acid, small molecule hyaluronic acid, cross-linked hyaluronic acid, parahydroxyacetophenone and pentanediol are added to deionized water and evenly mixed to obtain a microneedle mixture, wherein, based on the composition weight of the microneedle mixture, the content of modified hyaluronic acid is approximately 0.46wt%, the content of small molecule hyaluronic acid is approximately 2.31wt%, the content of cross-linked hyaluronic acid is 4.07wt%, the content of pentanediol is approximately 0.46wt%, the content of parahydroxyacetophenone is approximately 0.23wt% and the content of deionized water is approximately 92.47wt%. Then, using a dispensing method, a microneedle composition liquid weighing approximately 5g to 7g is dropped onto the master mold, and the microneedle composition liquid is allowed to cover the multiple holes on the master mold. The master mold containing the microneedle composition liquid is then placed in a vacuum oven and evacuated to a pressure of -700 mmHg to -760 mmHg. This causes the microneedle composition liquid to flow downward from the master mold base surface into the multiple holes of the master mold, covering the master mold base surface and all holes. Next, excess material is removed so that the surface of the microneedle composition liquid is flush with the base surface. The master mold containing the microneedle composition liquid is then placed in an environment of 30°C and a relative humidity of 10% to 30% for continuous drying for 1 hour. The microneedle composition liquid is dried into a plurality of microneedles 141, and the surface of each microneedle is lower than the base surface, thereby obtaining a master mold having a plurality of microneedles 141.

[0066] Next, appropriate amounts of high-viscosity hydroxypropyl methylcellulose, low-viscosity hydroxypropyl methylcellulose, vinyl pyrrolidone-vinyl acetate copolymer, p-hydroxyacetophenone, pentylene glycol, and silicone are added to deionized water and uniformly mixed to obtain a backing layer mixture. Based on the total weight of the backing layer mixture, the high-viscosity hydroxypropyl methylcellulose, low-viscosity hydroxypropyl methylcellulose, vinyl pyrrolidone-vinyl acetate copolymer, p-hydroxyacetophenone, pentylene glycol, and silicone defoamer are present in an amount of approximately 0.96 wt%, 0.48 wt%, 1.92 wt%, 0.24 wt%, 0.48 wt%, 0.02 wt%, and 95.90 wt% of deionized water. Subsequently, approximately 7 to 8.5 g of the backing layer mixture is dropped onto the master mold having the plurality of microneedles 13 using a dispensing method, so that the backing layer mixture covers the plurality of holes thereon. The master mold containing the backing layer mixture is then placed in a vacuum oven and evacuated to a pressure of -700 mmHg to -760 mmHg. This allows the backing layer mixture to flow downward from the reference surface into the multiple holes of the master mold, covering the reference surface and the microneedles in all the holes. The master mold containing the backing layer mixture is then dried for 24 hours at 23°C and a relative humidity of 30% to 50%. It is then dried for another 60 hours at 23°C and a relative humidity of 55% to 75%. This allows the backing layer mixture to dry into a backing layer that adheres to the microneedles and the master mold reference surface, thereby obtaining a master mold having a plurality of microneedles 141 and a backing layer 13.

[0067] On the other hand, a medical adhesive (3M TM Medical single-sided tape 1526) comprises a polyethylene film of about 0.09 mm as a base material 11 and an adhesive layer of about 0.04 mm 12, and the base material 11 and the adhesive layer 12 are penetrated to form a plurality of hollow channels 15. Figure 1B As shown, the width (L) of the substrate 11 and the adhesive layer 12 is 2 cm, the cross-sectional shape of each hollow channel 15 is cross-shaped, and the cross-sectional area of ​​each hollow channel 15 is 0.42 cm 2 .

[0068] Finally, after removing the master mold having the plurality of microneedles 141 and the backing layer 13, a polyethylene terephthalate (PET) film of 50 μm to 200 μm is selected as a release layer 16 and disposed on the adhesive layer 12 and next to the backing layer 13. A facial mask cloth is selected as a covering layer 17 and covered on the substrate 11 (i.e., on the side opposite to the adhesive layer 12), thereby obtaining the water-permeable microneedle patch 10 of Example 1.

[0069] Example 2: Water-permeable microneedle patch

[0070] The side cross-sectional structure of the water-permeable microneedle patch 10 of Example 2 is as follows: Figure 1A As shown, the manufacturing method is roughly the same as that of Example 1, except that the top view of the water-permeable microneedle patch 10 is as shown in FIG. Figure 2 .like Figure 2 As shown, the width (L) of the substrate 11 and the adhesive layer 12 is 2 cm, the cross-sectional shape of each hollow channel 15 is drop-shaped, the cross-sectional area of ​​each hollow channel 15 is 0.88 square centimeters, and the volume proportion of the hollow portion is 24v / v%.

[0071] Example 3: Water-permeable microneedle patch

[0072] The side cross-sectional structure of the water-permeable microneedle patch 10 of Example 3 is as follows: Figure 1A As shown, the manufacturing method is roughly the same as that of Example 1, except that the top view of the water-permeable microneedle patch 10 is as shown in FIG. Figure 3 .like Figure 3 As shown, the width (L) of the substrate 11 and the adhesive layer 12 is 2 cm, and the cross-sectional shapes of each hollow channel 15 are crescent-shaped and circular of varying sizes. The cross-sectional area of ​​the crescent-shaped and circular hollow channels 15 is 1.77 square centimeters, and the volume proportion of the hollow portion is 48.34 v / v%.

[0073] Example 4: Water-permeable microneedle patch

[0074] like Figure 4 and Figure 1B As shown, the water-permeable microneedle patch 10 of Example 4 comprises, from bottom to top, a substrate 11, a bonding layer 12, a backing layer 13, and a microneedle area 14, and a plurality of microneedles 141 are provided in the microneedle area 14, and the microneedles 141 are provided on the backing layer 13. The water-permeable microneedle patch 10 further comprises a hollow portion, which comprises a plurality of hollow channels 15, each hollow channel 15 is formed through the substrate 11 and the bonding layer 12 and is adjacent to the backing layer 13, the microneedles 141 are provided above the hollow portion, and the volume of the hollow portion (i.e., the total volume of the hollow channels 15) accounts for 11.58 v / v%. Specifically, the back layer 13 is formed between the adhesive layer 12 and the microneedle area 14. The back layer 13 has an upper surface and a lower surface relative to each other. The lower surface of the back layer 13 is bonded to the adhesive layer 12, and the microneedles 141 are formed on the upper surface of the back layer 13. The microneedles 141 can be arranged above each hollow channel 15.

[0075] In this embodiment, the water-permeable microneedle patch 10 further includes a release layer 16 , which is disposed on the adhesive layer 12 and located next to the backing layer 13 .

[0076] In this embodiment, the water-permeable microneedle patch 10 further includes a cover layer 17 and an adhesive layer 18. The cover layer 17 is disposed on the substrate 11 (on the side opposite the adhesive layer 12), and the adhesive layer 18 is disposed between the cover layer 17 and the substrate 11. Specifically, the adhesive layer 18 is located below the release layer 16, i.e., not below the microneedle area 14.

[0077] The manufacturing process of Example 4 is substantially the same as that of Example 1, except that an adhesive layer 18 is further provided between the cover layer 17 and the substrate 11 to tightly bond the cover layer 17 to the substrate 11 .

[0078] Example 5: Water-permeable microneedle patch

[0079] The side cross-sectional structure of the water-permeable microneedle patch 10 of Example 5 is as follows: Figure 4 As shown, the manufacturing method is roughly the same as that of Example 4, except that the top view of the water-permeable microneedle patch 10 is as shown in FIG. Figure 2 shown.

[0080] Example 6: Water-permeable microneedle patch

[0081] The side cross-sectional structure of the water-permeable microneedle patch 10 of Example 6 is as follows: Figure 4 As shown, the manufacturing method is roughly the same as that of Example 4, except that the top view of the water-permeable microneedle patch 10 is as shown in FIG. Figure 3 shown.

[0082] Example 7: Water-permeable microneedle patch

[0083] The structure of the water-permeable microneedle patch of Example 7 is as follows Figure 1A and Figure 2 As shown, its preparation method is generally similar to that of Example 2, except that the composition of the backing layer mixture is different from that of Example 2. The backing layer mixture of Example 7 comprises vinyl pyrrolidone-vinyl acetate copolymer, low-viscosity hydroxypropyl methylcellulose, sodium hyaluronate, dipotassium glycyrrhizate, methylisothiazolinone, lactobacillus fermentation product, and deionized water, wherein, relative to the composition weight of the backing layer, the content of vinyl pyrrolidone-vinyl acetate copolymer is approximately 1.6wt%, the content of low-viscosity hydroxypropyl methylcellulose is approximately 0.4wt%, the content of sodium hyaluronate is approximately 1.0wt%, the content of dipotassium glycyrrhizate is approximately 0.1wt%, the content of lactobacillus fermentation product is approximately 0.8wt%, the content of methylisothiazolinone is 0.07wt%, and the content of deionized water is approximately 96.03wt%.

[0084] See Figure 1AThe structure of the water-permeable microneedle patch 10 of Examples 1 to 3 and 7 creates the following mechanism: When an active substance is applied to the water-permeable microneedle patch 10, because the cover layer 17 is made of a water-permeable material, the active substance can penetrate the cover layer 17, pass through the hollow channels 15, and contact the backing layer 13. Then, it interacts with the microneedles 141, and is ultimately transported to the epidermis or dermis for dissolution and release. Thus, the structural arrangement of the hollow channels 15 improves the dissolution rate of the microneedles 141, thereby shortening the use time.

[0085] See Figure 4 , the structure of the water-permeable microneedle patch 10 of Examples 4 to 6 can also cause the mechanism described above: that is, when the active substance is applied to the water-permeable microneedle patch 10, the active substance can sequentially pass through the covering layer 17, through the hollow channels 15 and the back layer 13, and then interact with the microneedles 141, so that the microneedles 141 can increase their dissolution rate, thereby achieving the effect of shortening the use time. It should be noted that, since the adhesive layer 18 is not located below the microneedle area 14, the adhesive layer 18 will not hinder the interaction between the hollow channels 15, the back layer 13 and the microneedles 141. In addition, the adhesive layer 18 is more helpful in reducing the gap between the covering layer 17 and the substrate 11, so that fewer bubbles that hinder the dissolution rate are generated. In short, the provision of the adhesive layer 18 helps to further improve the dissolution rate of the microneedles 141.

[0086] Comparative Example 1: Microneedle Patch

[0087] The structure of the microneedle patch of Comparative Example 1 is as follows Figure 9 As shown, it comprises, from bottom to top, a substrate 11, an adhesive layer 12, a backing layer 13, and a microneedle area 14. The microneedle area 14 contains a plurality of microneedles 141, which are disposed on the backing layer 13. The fabrication process of Comparative Example 1 is similar to that of Example 1, except that the substrate 11 and adhesive layer 12 of Comparative Example 1 do not have hollow portions. The rest of the fabrication process follows that described in Example 1.

[0088] Test Example 1: Mechanical Strength Test of Microneedles

[0089] This test example uses the water-permeable microneedle patches of Examples 1 to 3 and the microneedle patch of Comparative Example 1 to perform mechanical strength tests on the microneedles. Since the covering layer has the function of buffering and absorbing stress, when performing the microneedle mechanical strength tests in Examples 1 to 3, the covering layer is removed to ensure the accuracy of the mechanical strength tests. In this test example, the water-permeable microneedle patches of Examples 1 to 3 and the microneedle patch of Comparative Example 1 are placed in a universal material testing machine (instrument model 3343, purchased from INSTRON), the displacement is set to 10 millimeters (mm), and a compression test is performed at a speed of 66 mm / min, while collecting 500 compression stress values ​​per second. The mechanical strength of the water-permeable microneedle patches of Examples 1 to 3 and Comparative Example 1 is as follows Figure 5 shown.

[0090] Since the water-permeable microneedle patches of Examples 1 to 3 all have hollow portions, the mechanical strengths measured are all lower than those of Comparative Example 1 which does not have a hollow portion. Figure 5 It can be found that when the volume of the hollow part is larger, the measured mechanical strength is lower. Figure 5 The results show that the mechanical strength of the microneedles of the water-permeable microneedle patches of Examples 1 to 3 is higher than 0.058N / needle. This mechanical strength can ensure that the microneedles can pierce the stratum corneum without bending or breaking, indicating that the water-permeable microneedle patch of the present disclosure can ensure that the microneedles can penetrate the subcutaneous tissue and provide the desired effect.

[0091] Test Example 2: Microneedle Solubility Determination

[0092] This test example uses the water-permeable microneedle patches of Examples 1 to 7 and the microneedle patch of Comparative Example 1 to perform microneedle solubility tests. First, the water-permeable microneedle patches of Examples 1 to 7 and the microneedle patch of Comparative Example 1 are respectively covered on the skin of the same subject, and 0.5 ml of maintenance liquid is dropped on the covering layer, and the microneedle solubility after 15 minutes and 30 minutes is recorded. The microneedle solubility is calculated as follows: (the number of completely dissolved microneedles × the volume of a single microneedle + the number of partially dissolved microneedles × the height of the partially dissolved microneedles / the average initial height of the microneedles × the volume of a single microneedle) / (the total number of microneedles × the volume of a single microneedle). Table 1 lists the volume ratios of the hollow parts of Examples 1 to 7, as well as the microneedle solubility test results of Examples 1 to 7 and Comparative Example 1 after 15 minutes and 30 minutes. Figures 6A to 6D 、 Figures 7A to 7D as well as Figures 8A to 8BPhotos of the microneedle dissolution in Examples 2, 5, and 7 and Comparative Example 1 are presented. The ingredients of the maintenance solution are glycerin, butylene glycol, betaine, p-hydroxyacetophenone, 1,2-hexamediol, panthenol, babassu oil glycereth-8 esters, PEG-6 caprylic / capric glycerides, dipotassium glycyrrhizate, sodium hyaluronate, and deionized water.

[0093] Table 1: Volume ratio of the hollow portion, microneedle solubility at 15 minutes, and microneedle solubility at 30 minutes of Examples 1 to 7 and Comparative Example 1.

[0094]

[0095] As can be seen from the results in Table 1 above, the microneedle solubility of the water-permeable microneedle patches of Examples 1 to 6 is higher than 50% at 30 minutes, while the microneedle solubility of Comparative Example 1 is only 44.87% at 30 minutes, indicating that the water-permeable microneedle patch of the present disclosure has a faster microneedle dissolution rate within a 30-minute usage time. Furthermore, since the volume proportion of the hollow portion of Examples 2 and 5 is controlled at 20v / v% to 50v / v%, the microneedle solubility thereof at 30 minutes is higher than 60%; since the volume proportion of the hollow portion of Examples 3 and 6 is controlled at 30v / v% to 50v / v%, the microneedle solubility thereof at 30 minutes is higher than 90%. It can be seen that when the volume proportion of the hollow portion is higher, the microneedle solubility at 30 minutes will also be higher. Furthermore, a detailed examination of Examples 1 to 3 and Examples 4 to 6 reveals that the microneedle solubility of the water-permeable microneedle patches of Examples 4 to 6 after 30 minutes is higher than that of Examples 1 to 3. The microneedle solubility of Examples 2 and 5 is 62.49% and 72.43%, respectively, with a difference of about 10%. This shows that when an adhesive layer is provided between the covering layer and the substrate, the gap between the two is smaller, and fewer bubbles are generated, which increases the dissolution rate of the microneedles and achieves the effect of shortening the usage time. Furthermore, by comparing the solubility of the microneedles in Comparative Example 1 at 30 minutes with that at 15 minutes, it was found that the solubility of the microneedles in Comparative Example 1 only increased from 42.37% to 44.87%, an increase of only 2.4%; however, a detailed examination of Examples 2 to 6 showed that the solubility of the microneedles increased by at least 6.24% (Example 2) and at most 15% (Example 4). It can be seen that the permeable microneedle patch containing a hollow portion does have the effect of accelerating the dissolution rate of the microneedles, and the effect is particularly apparent when the usage time is prolonged.

[0096] Furthermore, as can be seen from the results in Table 1 above, the microneedle solubility of Comparative Example 1 at 15 minutes was only 42.37%. In contrast, the microneedle solubility of the water-permeable microneedle patches of Examples 2 to 6 at 15 minutes was higher than that of the microneedle patch of Comparative Example 1. This shows that the water-permeable microneedle patch of the present disclosure still has the effect of a faster microneedle dissolution rate even with a shorter usage time. Further scrutiny of the microneedle solubility at 15 minutes also reveals that the microneedle solubility of Examples 2 and 5 is higher than 50%, and the microneedle solubility of Examples 3 and 6 is even higher than 80%, further confirming that when the volume proportion of the hollow portion is controlled between 20 v / v% and 50 v / v%, or even between 30 v / v% and 50 v / v%, the dissolution rate of the microneedles is faster.

[0097] The effects of the water-permeable microneedle patch disclosed herein can also be demonstrated by photographs of the actual dissolution of the microneedles. Figure 6A This is a top view of Example 2 before use. Figure 6B This is a top view of Example 2 at 15 minutes. Figure 6C The top view of Example 5 at 15 minutes and Figure 6D This is a top view of Example 7 after 15 minutes of use. A careful examination of the four figures shows that the water-permeable microneedle patch of Example 2 has obvious microneedle structures in both the hollow part and the area outside the hollow part before use; Figure 6B In Example 2, after 15 minutes of use, the microneedle structure in the area covered by the hollow portion has been partially dissolved, but clear microneedle structures can still be seen in the area outside the hollow portion. Figure 6C After 15 minutes, in Example 5, since there is a glue layer between the covering layer and the substrate, fewer bubbles are mixed in to affect the dissolution rate of the microneedles. It can be seen that there is no clear microneedle structure in the area covered and uncovered by the hollow part, which proves that its dissolution rate is better than that of Example 2. Finally, let's look at Figure 6D In Example 7, the backing layer was further controlled to dissolve rapidly within 15 minutes. Figure 6D As shown, in the area covered by the hollow portion, the microneedle structure and the backing layer have been dissolved, with a better dissolution rate.

[0098] See again Figures 7A to 7D , Figure 7A This is a side view of the microneedle before use in Example 1, Figures 7B to 7D The following are the side views of the microneedles after 30 minutes of Comparative Example 1, Example 2, and Example 5. Figure 7A It can be seen that the microneedle before use has the highest needle height; Figure 7B It can be seen that the microneedle shape of Comparative Example 1 remained almost intact after 30 minutes, and only the needle tip began to dissolve; Figure 7C and7D It can be seen that the needle heights of Examples 2 and 5 are lower than those of Comparative Example 1, indicating that the solubility of the microneedles of both examples after 30 minutes is better than that of Comparative Example 1. Figure 7D It can be found that in Example 5, since an adhesive layer is included between the cover layer and the substrate, the dissolution effect of the microneedles is better, and almost no microneedles are left.

[0099] In addition, the effects of further controlling the composition of the back layer can also be Figure 8A and 8B In the comparison. Figure 8A In Example 2, after 15 minutes of testing on the subject's skin, no residual microneedle dissolving liquid was found; Figure 8B In the experiment, after the subject applied the water-permeable microneedle patch of Example 7, a lot of residual liquid after the dissolution of the microneedles was visible on the subject's skin, confirming that the back layer components can dissolve the back layer more quickly, thereby achieving the effect of shortening the use time.

[0100] In summary, through the structural setting of the hollow part and the control of the volume ratio of the hollow part, the water-permeable microneedle patch provided by the present invention not only has good mechanical strength to ensure that the microneedles can enter the subcutaneous tissue without bending or breaking, but also has the effect of improving the dissolution rate of the microneedles, thereby shortening the usage time, thereby achieving the effect of improving the convenience of use and reducing risks.

Claims

1. A water-permeable microneedle patch, comprising a substrate, an adhesive layer, a backing layer, and a microneedle area, wherein a plurality of microneedles are disposed in the microneedle area, the microneedles being disposed on the backing layer. The water-permeable microneedle patch further comprises a hollow portion, the hollow portion comprising at least one hollow channel, the hollow channel being formed through the substrate and the adhesive layer and adjacent to the backing layer, the microneedles being disposed above the hollow portion, and the volume of the hollow portion relative to the total volume of the substrate and the adhesive layer being greater than or equal to 10 volume percent and less than or equal to 50 volume percent.

2. The water-permeable microneedle patch according to claim 1, wherein: The volume of the hollow portion relative to the total volume of the substrate and the adhesive layer is greater than or equal to 20 volume percent and less than or equal to 50 volume percent.

3. The water-permeable microneedle patch according to claim 1, wherein The volume of the hollow portion relative to the total volume of the substrate and the adhesive layer is greater than or equal to 30 volume percent and less than or equal to 50 volume percent.

4. The water-permeable microneedle patch according to claim 1, wherein The back layer has an upper surface and a lower surface opposite to each other. The lower surface of the back layer is bonded to the bonding layer, and the micro needles are formed on the upper surface of the back layer.

5. The water-permeable microneedle patch according to claim 1, wherein The microneedles are arranged above the hollow channel.

6. The water-permeable microneedle patch according to claim 1, wherein: The backing layer comprises vinyl pyrrolidone-vinyl acetate, hydroxypropyl methylcellulose, sodium hyaluronate, dipotassium glycyrrhizate, lactobacillus fermentation product, methylisothiazolinone and deionized water.

7. The water-permeable microneedle patch according to claim 1, wherein: The backing layer comprises vinyl pyrrolidone-vinyl acetate copolymer, hydroxypropyl methylcellulose, pentylene glycol, organic silicon defoaming agent, p-hydroxyacetophenone and deionized water.

8. The water-permeable microneedle patch according to claim 1, wherein: The plurality of microneedles are composed of hyaluronic acid, pentylene glycol, p-hydroxyacetophenone and deionized water.

9. The water-permeable microneedle patch according to any one of claims 1 to 8, wherein The water-permeable microneedle patch further comprises a covering layer, which is located on a side of the substrate opposite to the adhesive layer.

10. The water-permeable microneedle patch according to claim 9, wherein: The water-permeable microneedle patch further comprises an adhesive layer, which is located between the covering layer and the substrate and is not located below the microneedle area.

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