Microneedle patch, percutaneous absorption composition, and soluble film

Abstract

The invention discloses a microneedle patch, a percutaneous absorption composition and a soluble film composition. The microneedle patch comprises a microneedle layer and a carrier layer. The microneedle layer comprises a substrate layer and a plurality of microneedles. The microneedles are formed by a solution containing pectin and hyaluronic acid, and are arranged on the substrate layer at intervals. The substrate layer has a first surface and a second surface opposite to each other. The plurality of microneedles are arranged on the first surface, and the microneedle layer is arranged on the carrier layer through the second surface of the substrate layer. The invention also discloses a percutaneous absorption composition, which comprises pectin and hyaluronic acid.

Description

Technical Field

[0001] The present invention relates to the field of transdermal drug delivery, and in particular to a microneedle patch, a transdermal absorption composition and a soluble film. Background Art

[0002] The microneedle patch (MNP) is a new transdermal drug delivery system (TDDS). The microneedles on the patch are very short and will not touch the nerves. Not only does it not cause the pain of subcutaneous injection, but it can also carry bioactive ingredients or drugs through the stratum corneum of the skin into the human body. MNP technology can be used in various fields such as medical beauty, medicine, and preventive medicine. Summary of the invention

[0003] The present invention provides a microneedle patch, which is helpful to improve the undesirable conditions in the manufacturing process and increase the yield and production rate.

[0004] The invention also provides a soluble film with good film-forming property.

[0005] The present invention also provides a transdermal absorption composition, which helps to improve the yield and production rate of the microneedle patch and the film-forming property of the soluble film, and can provide a sustained-release effect of the transdermal drug delivery system.

[0006] To achieve one or part or all of the above purposes or other purposes, one embodiment of the present invention provides a microneedle patch, comprising a microneedle layer and a carrier layer. The microneedle layer comprises a base layer and a plurality of microneedles, wherein the plurality of microneedles are formed by a solution containing pectin and hyaluronic acid and are disposed on the base layer at intervals. The base layer has a first surface and a second surface opposite to each other, wherein the plurality of microneedles are located on the first surface, and the microneedle layer is disposed on the carrier layer with the second surface of the base layer.

[0007] In one embodiment of the present invention, the weight ratio of pectin to hyaluronic acid in the solution containing pectin and hyaluronic acid is 0.3-1.

[0008] To achieve one, part or all of the above-mentioned purposes or other purposes, another embodiment of the present invention further provides a transdermal absorption composition, which contains pectin and hyaluronic acid, and the sum of the pectin content and the hyaluronic acid content accounts for 1-2 wt% of the transdermal absorption composition, and the weight ratio of pectin to hyaluronic acid is 0.3-1.

[0009] To achieve one, part, or all of the above purposes or other purposes, another embodiment of the present invention further provides a soluble film prepared from the above-mentioned transdermal absorption composition.

[0010] Since the present invention uses pectin and hyaluronic acid as the components of the microneedle layer, a microneedle layer with good integrity and flatness can be formed, which is conducive to the formation of the microneedle patch and ensures the yield and production rate of the microneedle patch.

[0011] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments, but is not intended to limit the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 FIG. 4 is a cross-sectional schematic diagram of a microneedle patch according to an embodiment of the present invention.

[0013] Figure 2 FIG. 4 is a schematic flow chart of a method for manufacturing a microneedle patch according to an embodiment of the present invention.

[0014] Figures 3A-3C FIG. 4 is a schematic diagram of an implementation method of a microneedle patch according to the first embodiment of the present invention.

[0015] Figure 4 FIG. 4 is a schematic diagram of an implementation method of a microneedle patch according to a second embodiment of the present invention.

[0016] Figure 5 Schematic diagram of a photograph of a microneedle layer of a comparative example of the present invention.

[0017] Figure 6 Schematic diagram of the hourly dissolution rate of the microneedle layer of the embodiment of the present invention and the comparative example.

[0018] Figure 7 FIG. 4 is a schematic cross-sectional view of a soluble film according to an embodiment of the present invention.

[0019] Among them, the reference numerals

[0020] 1: Microneedle patch

[0021] 10, 10a, 10': Microneedle layer (membrane)

[0022] 10b: Soluble membrane

[0023] 100, 100': Microneedle

[0024] 150: Basal layer

[0025] 151: Side 1

[0026] 152: Side 2

[0027] 20: Carrier layer

[0028] 30: Release film

[0029] 301: Hollow area

[0030] 40: Pectin and hyaluronic acid solution (transdermal absorption composition)

[0031] 70: Male model

[0032] 710: Bearing seat

[0033] 720: Microneedle structure

[0034] 80': polymer material

[0035] 80: Master mold

[0036] 810: Space

[0037] 820: Cone hole

[0038] S910~S950: Steps

[0039] F: Force

[0040] C: Crop tool DETAILED DESCRIPTION

[0041] The aforementioned and other technical contents, features and effects of the present invention will be clearly presented in the following detailed description of a preferred embodiment with reference to the drawings. The directional terms mentioned in the following embodiments are only with reference to the directions of the attached drawings. Therefore, the directional terms used are used to illustrate and not to limit the present invention. In addition, the terms "first", "second", etc. mentioned in this specification or the scope of the patent application are only used to name the name of the element or to distinguish different embodiments or scopes, and are not used to limit the upper or lower limit of the number of elements.

[0042] The present invention provides a microneedle patch that can improve the adverse conditions in the manufacturing process and increase the yield and production rate. The microneedle patch provided by the present invention can be used for transdermal drug delivery and transdermal absorption, and can therefore be used as a carrier for several biologically active ingredients, pharmaceutically active ingredients or a combination thereof. The biologically active ingredients are not limited to natural substances such as plants or their extracts, but can also be artificially synthesized substances. In the present invention, biologically active ingredients mean ingredients that can produce biological effects on humans or other organisms, such as ingredients that change human physiological functions and biochemical metabolism. Biologically active ingredients are not limited to achieving therapeutic or preventive effects, but biologically active ingredients with therapeutic or preventive effects can be equivalent to pharmaceutically active ingredients. The pharmaceutically active ingredients described in the present invention include natural substances and artificially synthesized substances. The microneedle patch provided by the present invention can further provide a sustained-release effect, extending the release period of biologically active ingredients, pharmaceutically active ingredients or a combination thereof in the human body or other organisms.

[0043] Figure 1 FIG. 1 is a cross-sectional schematic diagram of a microneedle patch according to an embodiment of the present invention. Figure 1As shown, the microneedle patch 1 includes a microneedle layer 10 and a carrier layer 20. The microneedle layer 10 includes a base layer 150 and a plurality of microneedles 100, and the microneedles 100 are arranged on the same side of the base layer 150 at intervals. The diameter of the microneedle 100 is the thicker the closer to the base layer 150, and specifically, the shape can be, for example, a pyramid or a cone. The length of the microneedle 100 can be 100 to 1500 μm, for example, 100 μm, 500 μm, 800 μm, 1000 μm, 1500 μm. The base layer 150 has an appropriate thickness, for example, 5 to 50 μm, and has a first surface 151 and a second surface 152 opposite to each other. The microneedles 100 are all arranged on the same surface, for example, the first surface 151, and the other surface, such as the second surface 152, can be used for connecting the microneedle layer 10 with the carrier layer 20.

[0044] In an embodiment of the present invention, the microneedle 100 is formed by a solution containing pectin (INCI: Pectin) and hyaluronic acid (hereinafter referred to as a pectin and hyaluronic acid solution). It should be noted that the hyaluronic acid includes hyaluronic acid (Hyaluronic acid) itself and its derivatives. The solution is an aqueous solution, and preferably an aqueous solution. The pectin and hyaluronic acid solution can be injected into a mold and then dried to form the microneedle 100. In a preferred embodiment of the present invention, the base layer 150 is also formed by a solution containing pectin and hyaluronic acid. Further, the aqueous solution containing pectin and hyaluronic acid can be injected into a mold and then dried to form the microneedle layer 10 in one piece.

[0045] Hyaluronic acid and pectin are biocompatible polymer compounds. In the present invention, biocompatibility means that the material, compound or composition will not release toxic or harmful substances, causing local or systemic adverse reactions such as inflammatory reactions, immune reactions, and toxic reactions in the human body or other organisms. Therefore, the microneedle layer 10 formed by pectin and hyaluronic acid solution can contact the human body without safety concerns, and can be used as a carrier for transdermal drug delivery and transdermal absorption. In a preferred embodiment of the present invention, due to biocompatibility, the microneedle layer 10 can be degraded over time when implemented in transdermal drug delivery and transdermal absorption, and does not cause adverse reactions in the human body or other organisms. While degrading (hereinafter also referred to as dissolving), the bioactive ingredients and drug active ingredients contained in the microneedle 100 are gradually released into the body to produce effects. The release period of the bioactive ingredients and drug active ingredients may vary depending on the degradation rate of the microneedle 100.

[0046] In addition to being biocompatible, the hyaluronic acid and pectin solution also help the microneedle layer 10 to be intact, flat and not curled, and have appropriate elasticity and avoid fragmentation. Due to the good shape and structure of the microneedle layer 10, the microneedles 100 therein also have good shapes and structures, and can achieve the effect of puncture. The flatness and integrity of the microneedle layer 10 also contribute to the yield and production rate of the microneedle patch 1, for example, ensuring that the carrier layer 20 can be well disposed on the microneedle layer 10.

[0047] Hyaluronic acid and pectin are further formulated into a solution containing pectin and hyaluronic acid in an appropriate ratio. The appropriate ratio between hyaluronic acid and pectin helps to achieve the aforementioned integrity, flatness and appropriate elasticity to a higher degree. In a preferred embodiment of the present invention, the weight ratio of pectin to hyaluronic acid is 0.3-1, such as 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, and in a more preferred embodiment, it is 0.3-0.7, such as 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7. To achieve a weight ratio of 0.3 to 1, for example, when the amount of hyaluronic acid accounts for 1 wt% of the solution, that is, 1 wt% of the weight of the microneedle 100, the amount of pectin can be 0.3 to 1 wt%, such as 0.3 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.7 wt%, 0.8 wt%, 0.9 wt%, 1 wt%. The sum of the weights of pectin and hyaluronic acid is preferably 1 to 2 wt% of the solution in the embodiment of the present invention, that is, 1 to 2 wt% of the weight of the microneedle 100, such as 1 wt%, 1.5 wt%, 2 wt%. In an embodiment of the present invention, the solid content in the solution, such as the total amount of pectin and hyaluronic acid, can further affect the thickness of the formed microneedle layer 10, and by adjusting the total amount of pectin and hyaluronic acid, the microneedle layer 10 can have an appropriate thickness of 5 to 50 μm, for example, 5 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μm, and 50 μm.

[0048] The microneedle 100 further contains a bioactive ingredient, a pharmaceutically active ingredient, or a combination thereof. The bioactive ingredient may be, for example, vitamin B, vitamin C, salicylic acid, tranexamic acid, ceramide, nicotinamide, ergothioneine, collagen, various plant extracts, and various compounds with cosmetic effects, but is not limited thereto. The pharmaceutically active ingredient may be, for example, an analgesic, an antihistamine, or insulin, but is not limited thereto. Based on the fact that the degradation rate of the microneedle 100 may affect the release period of the bioactive ingredient and the pharmaceutically active ingredient, the ingredients that are intended to act during a specific period may be further selected. For example, a bioactive ingredient or a pharmaceutically active ingredient with a sustained release requirement may be selected, and the release and action period of these ingredients may be extended by the sustained release effect provided by the microneedle 100.

[0049] The method for producing the microneedle patch 1 is exemplified below.

[0050] Figure 2 FIG. 1 is a schematic diagram of a process for manufacturing a microneedle patch according to an embodiment of the present invention. Figure 2 and Figures 3A to 3CAs shown, it includes steps S910 to S950. Step S910 includes: providing a male mold, and the provided male mold has a support seat and a plurality of microneedle structures, and the plurality of microneedle structures are arranged on the support seat at intervals. Step S920 includes: distributing polymeric material to the male mold and forming a female mold. Step S930 includes: distributing pectin and hyaluronic acid solution to the female mold and forming a microneedle layer. Step S940 includes: setting a carrier layer on the opposite side of the microneedle layer where a plurality of microneedles are arranged. Step S950 includes: separating the microneedle layer and the female mold.

[0051] The male mold 70 in step S910 is a metal mold. The embodiment of the present invention does not limit the material of the male mold 70, but for example, it can be titanium, copper, aluminum, nickel, tungsten, stainless steel, titanium alloy, nickel alloy, aluminum alloy, copper alloy. Figure 3A As shown, a plurality of microneedle structures 720 are spaced apart from each other and are disposed on a support seat 710 at an appropriate distribution density. The shape of the microneedle structure 720 may be, for example, a cone, a triangular pyramid, or a quadrangular pyramid, and the height may be, for example, 100 to 1500 μm. In addition, the spacing between adjacent microneedle structures 720 may be, for example, 0.5 to 5 mm. The polymer material 80' of step S920 may be, for example, polyethylene, polypropylene, polylactic acid, polybutylene succinate, polydimethylsiloxane, but is not limited thereto. Figure 3A As shown, step S920 further includes distributing the polymer material 80 ′ to the support 700 and the plurality of microneedle structures 720 thereon, so that the master mold 80 forms a plurality of conical holes 820 . The shape of the conical holes 820 corresponds to the shape of the microneedles 100 .

[0052] like Figure 3BAs shown, step S930 may further include the preparation of pectin and hyaluronic acid solution 40. Since the microneedle layer 10 formed by the pectin and hyaluronic acid solution 40 can be used as a carrier for transdermal drug delivery and transdermal absorption, the pectin and hyaluronic acid solution 40 can also be called a transdermal absorption composition. The preparation of the pectin and hyaluronic acid solution 40 mainly includes weighing an appropriate amount of solvent, pectin and hyaluronic acid, and then dissolving the pectin and hyaluronic acid in the solvent. The solvent used is preferably water. The purity of the water is preferably above the level of distilled water, and more preferably double distilled water (ddH2O). Pectin and hyaluronic acid can generally be mixed in water in a powder state, wherein the weight ratio of pectin powder to hyaluronic acid powder is preferably 0.3 to 1, for example 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1. In the present embodiment, hyaluronic acid with a molecular weight less than 800,000 Da may be further used, such as 800,000 Da, 500,000 Da, 100,000 Da, 80,000 Da, 50,000 Da, 10,000 Da, 8,000 Da, 5,000 Da, 1,000 Da. In some embodiments, the molecular weight of hyaluronic acid may be between 3,000 and 800,000 Da. Hyaluronic acid with different molecular weights may be combined for preparing the solution, or hyaluronic acid with a single molecular weight may be used for preparing the solution.

[0053] In an embodiment of the present invention, the weight of pectin and hyaluronic acid is preferably 1 to 2 wt% of the solution, such as 1wt%, 1.5 wt%, and 2 wt%. Pectin and hyaluronic acid aqueous solutions generally have viscosity. The viscosity may be, for example, between 15 and 5000 cps, such as 15 cps, 50 cps, 100 cps, 250 cps, 500 cps, 1000 cps, 2000 cps, 3000 cps, 4000 cps, and 5000 cps, but is not limited thereto. In principle, as long as the formation of the microneedle layer 10 is not hindered, the embodiment of the present invention has no restrictions on viscosity. Step S930 also includes a bubble removal procedure. The bubble removal procedure is generally performed after the solution containing pectin and hyaluronic acid is distributed. In this procedure, bubbles in the solution are discharged to prevent the formation of holes in the microneedle layer 10. The degassing process can be carried out naturally by the weight of the solution, or can be accelerated by other means such as vibration or heat. The aforementioned viscosity does not hinder the formation of the microneedle layer 10, for example, it can be such that it does not hinder the effective degassing.

[0054] Step S930 may further include adding bioactive ingredients, active pharmacological ingredients or a combination thereof to the pectin and hyaluronic acid solution. The definitions and examples of bioactive ingredients and active pharmacological ingredients are as described above and are not repeated here. The amount of bioactive ingredients, active pharmacological ingredients or a combination thereof added may be adjusted according to, for example, their dosage requirements, the release period of the claims, and the degradation period of the carrier. For example, the amount of analgesic added may be, for example, several milligrams to hundreds of milligrams. In some embodiments of the present invention, the pectin and hyaluronic acid solution added with bioactive ingredients, active pharmacological ingredients or a combination thereof may be first distributed to the conical hole 820 of the master mold 80, and then the pectin and hyaluronic acid solution without bioactive ingredients, active pharmacological ingredients or a combination thereof may be distributed to the space 810 above the conical hole 820, so that the formed microneedle layer 10 contains bioactive ingredients, active pharmacological ingredients or a combination thereof only in the microneedles 100.

[0055] Step S930 also includes a drying process. The drying process is generally followed by the degassing process. This process can form a film composed of pectin and hyaluronic acid, that is, the microneedle layer 10. The drying process can be carried out naturally at normal temperature and humidity, or at a specific temperature and humidity, for example, by drying by a number of means such as baking equipment, drying equipment, and heating equipment. In some embodiments of the present invention, drying can be carried out by baking equipment at an appropriate temperature. Figure 3B As shown, the volume of the film formed after the drying process, especially the base layer 150, may be reduced compared to the volume of the solution, but this is normal. In addition, the microneedle layer 10 should present a complete shape. For example, when the mother mold 80 is roughly rectangular with a specific length and width, the microneedle layer 10 should have a considerable length and width in the same direction. In addition, the microneedle layer 10 should be flat and not curled, and preferably, have appropriate elasticity and not break.

[0056] Furthermore, the ratio between pectin and hyaluronic acid in the embodiment of the present invention helps to ensure that the microneedle layer 10 is intact in shape, flat and not curled, and has appropriate elasticity without breaking. Further, under the same drying conditions, the film 10 formed by the solution with a weight ratio of pectin to hyaluronic acid of 0.3 to 1 can better meet the requirements of intact shape and flatness without curling. The complete and flat film 10, that is, the integrity and flatness of the microneedle layer 10, is helpful for the subsequent steps. The integrity and flatness of the microneedle layer 10 can also ensure that the shape and structure of its microneedles 100 are symmetrical and complete, without skewness or breakage, and can achieve the effect of puncture. The present invention verifies the relationship between the weight ratio of pectin and hyaluronic acid and film-forming properties, and the results are shown in Table 1 below:

[0057] Table 1

[0058] No. Hyaluronic acid aqueous solution (wt %) Pectin (wt %) Pectin / hyaluronic acid weight ratio Integrity (water repellency) Flatness Membrane status 1 0.5 wt% 0 wt% 0 Water repellent curly Will not break 2 0.6 wt% 0 wt% 0 Water repellent curly Will not break 3 0.85 wt% 0 wt% 0 Water repellent curly Will not break 4 1 wt% 0 wt% 0 Water repellent curly Will not break 5 1 wt% 0.2 wt% 0.2 Slight water repellent Micro-curl Will not break 6 1 wt% 0.3 wt% 0.3 No water smooth Will not break 7 1 wt% 0.4 wt% 0.4 No water smooth Will not break 8 1 wt% 0.5 wt% 0.5 No water smooth Will not break 9 1 wt% 0.6 wt% 0.6 No water smooth Will not break 10 1 wt% 0.7 wt% 0.7 No water smooth Will not break 11 1 wt% 0.8 wt% 0.8 No water smooth Flexible 12 1 wt% 0.9 wt% 0.9 No water smooth Too soft 13 1 wt% 1 wt% 1 No water smooth Too soft

[0059] In Table 1, No. 1 to 4 are comparative examples, which use hyaluronic acid solutions containing different weight percentages to form a membrane 10', and No. 5 to 13 are examples, which use pectin and hyaluronic acid solutions containing different pectin / hyaluronic acid weight ratios to form a membrane 10, wherein the solutions of No. 1 to 4 do not contain pectin. The results show that the membrane 10 formed by the solution with a weight ratio of pectin to hyaluronic acid of 0.3 to 1 has good integrity and flatness, wherein the membrane formed by the solution with a weight ratio of 0.3 to 7 has more appropriate elasticity and does not break. In comparison, as shown in Table 1 and Figure 5 In the comparative example shown, the film 10' formed by the solution with a weight ratio other than 0.3-1 was incomplete (water-repellent) and curled, and the microneedles 100' were distorted and broken.

[0060] like Figure 3B As shown, step S940 further includes disposing a release film 30 and a carrier layer 20 on the opposite side of the microneedle layer 10 with the microneedles 100, such as the second side 152 of the base layer 150. The release film 30 and the carrier layer 20 can be disposed on the base layer 150 in sequence, or can be combined first and then disposed on the base layer 150 together. In the embodiment of the present invention, the release film 30 is disposed between the carrier layer 20 and the base layer 150, and generally has a plurality of hollow areas 301. The release film 30 and its hollow areas 301 are helpful for subsequently dividing the microneedle layer 10 into a plurality of parts, but are not limited thereto. Figure 4 As shown, the carrier layer 20 may be directly disposed on the base layer 150 without passing through the release layer 30. The material of the carrier layer 20 may be, for example, a synthetic or natural fabric, a synthetic or natural polymer, such as a woven, non-woven or knitted fabric. The carrier layer 20 is preferably compliant and flexible to facilitate smooth attachment to the surface of the organism. For example, the carrier layer 500 may be, for example, a film or a piece of cloth. The material of the carrier layer 20 may also be selected based on a number of functional requirements such as waterproof, breathable, antibacterial, odor, aesthetics, and feel. In addition, it may also be selected based on medical consumables available on the market, such as bandages, tapes, and patches.

[0061] like Figure 3C and Figure 4 As shown, step S940 may further include applying force F to the carrier layer 20 toward the microneedle layer 10 to promote the bonding between the carrier layer 20 and the microneedle layer 10. Step S950 may further include removing the microneedle layer 10 bonded to the carrier layer 20 from the master mold 80, thereby completing the manufacture of the microneedle patch 1. In addition, in some embodiments of the present invention, the microneedle layer 10 may be further cut according to the shape of each hollow area 301 to divide the microneedle layer 10 into a plurality of microneedle layers 10a. Cutting may be performed by a cutting tool C. The cutting tool C is, for example, but not limited to, a punch die or a laser knife.

[0062] As mentioned above, the microneedle patch 1 of the embodiment of the present invention can provide a sustained release effect, wherein due to the biocompatibility of the microneedle layer 10, the microneedles 100 can be degraded over time, and the biologically active ingredients and active pharmaceutical ingredients carried therein are released within a specific period based on the degradation rate. The present invention also tests the relationship between the components of the microneedle layer 10 and its degradation rate (hereinafter also referred to as the dissolution rate), and finds the relationship between the weight ratio of pectin and hyaluronic acid and the dissolution rate, and the results are shown in Table 2 below:

[0063] Table 2

[0064] No. Hyaluronic acid aqueous solution (wt %) Pectin (wt %) Pectin / hyaluronic acid weight ratio 4-hour dissolution rate 6 hours dissolution rate 1 0.5 wt% 0 wt% 0 100% 100% 2 0.6 wt% 0 wt% 0 100% 100% 3 0.85 wt% 0 wt% 0 100% 100% 4 1 wt% 0 wt% 0 100% 100% 5 1 wt% 0.2 wt% 0.2 80% 100% 6 1 wt% 0.3 wt% 0.3 40% 75% 7 1 wt% 0.4 wt% 0.4 40% 60% 8 1 wt% 0.5 wt% 0.5 35% 60% 9 1 wt% 0.6 wt% 0.6 35% 60% 10 1 wt% 0.7 wt% 0.7 35% 60% 11 1 wt% 0.8 wt% 0.8 35% 60% 12 1 wt% 0.9 wt% 0.9 35% 60% 13 1 wt% 1 wt% 1 35% 60%

[0065] Table 2 shows that in the same period, such as 4 hours and 6 hours, the dissolution rate of the film 10 of No. 5 to 13 is lower than the dissolution rate of the film 10' of No. 1 to 4, wherein the solution of No. 1 to 4 does not contain pectin. It can be seen that pectin should help provide a sustained release effect and extend the release period of the biologically active ingredient, the pharmaceutically active ingredient, or a combination thereof. As shown in Table 2, the dissolution rate of the film 10 formed by the solution with a weight ratio of pectin to hyaluronic acid greater than 0.2 (film 10 of No. 6 to 13) after 6 hours did not reach 100%, indicating that it can make the release period of the biologically active ingredient, the pharmaceutically active ingredient, or a combination thereof exceed 6 hours, providing a slower release effect.

[0066] The present invention further compares the degradation rate of microneedles in the embodiment microneedle patch 1 and commercially available microneedle patches. As mentioned above, the microneedle layer 10 of the microneedle patch 1 contains pectin and hyaluronic acid in a weight ratio of 0.3 to 1, while the commercially available microneedle patch does not contain pectin. The test method is to apply the microneedle patch 1 of the present invention and the commercially available microneedle patch in groups on different individuals (n=3), and then collect the microneedle patch 1 and the commercially available microneedle patch from time to time to calculate the degradation rate of the microneedles 100 of the embodiment of the present invention and the microneedles of the commercially available patch. Figure 6 As shown, the square points in each hour are the degradation rates of the microneedles 100 of the microneedle patch 1 of the embodiment on individuals 1, 2, and 3 after that hour. The solid curve is obtained by averaging each hour, reflecting the hourly dissolution rate of the microneedles 100. The circles in each hour are the degradation rates of the microneedles of the commercially available microneedle patch on individuals 1, 2, and 3 after that hour, and the dotted curve is obtained by averaging them. Figure 6 As shown, the microneedle 100 of the embodiment of the present invention degrades at a nearly stable rate from the 1st to the 6th hour, and the dissolution rate has not yet reached 100%. In contrast, the degradation of the commercially available patch microneedle ends at the latest after 4 hours, reflecting that the bioactive ingredients and drug active ingredients cannot be continuously released after 4 hours.

[0067] The present invention also provides a soluble film, which is prepared from the aforementioned percutaneous absorption composition. As mentioned above, the percutaneous absorption composition is a pectin and hyaluronic acid solution, and further contains a bioactive ingredient, an active pharmacological ingredient or a combination thereof. Because the materials, compounds or compositions used to prepare the soluble film have biocompatibility, the soluble film is endowed with solubility. Solubility can also be called degradability.

[0068] In the embodiment of the present invention, Figure 7 As shown, the soluble film 10b may further include a base layer 150 and a plurality of microneedles 100, and the plurality of microneedles 100 are arranged on the same side of the base layer 150 at intervals. The side of the base layer 150 on which the plurality of microneedles 100 are arranged is referred to as the first side 151. The soluble film 10b can be used as a microneedle film, or can be used to make the microneedle patch 1 as described above. In a preferred embodiment of the present invention, the pectin and hyaluronic acid solution used to prepare the soluble film 10b has a pectin / hyaluronic acid weight ratio of 0.3 to 1, so it has good film-forming properties: the shape is complete, flat and not curled, and has appropriate elasticity without breaking. Both the microneedle film and the microneedle patch 1 can be used as a transdermal drug delivery device.

[0069] The degradation of the soluble film 10b of the embodiment of the present invention preferably occurs under appropriate conditions. Further, the soluble film 10b preferably degrades under conditions higher than room temperature. The room temperature is preferably a temperature lower than 35°C, and more preferably lower than 30°C, such as 20-30°C. The degradable (dissolvable) temperature of the soluble film 10b is preferably above 35°C. For example, when the soluble film 10b is applied to an organism as a microneedle film or made into a microneedle patch 1, the body temperature of the organism can degrade the microneedle 100 to release bioactive ingredients, active pharmacological ingredients or a combination thereof. In some embodiments of the present invention, the microneedle 100 can be completely degraded after 8-10 hours at a temperature higher than room temperature, such as 35-40°C. In a preferred embodiment of the present invention, the degradation degree of the microneedle 100 at an appropriate temperature, such as 35-40°C, within 4 hours is less than 50%, so it can be further used as a sustained-release transdermal drug delivery device.

[0070] Of course, the present invention may have many other embodiments. Without departing from the spirit and essence of the present invention, those skilled in the art may make various corresponding changes and modifications based on the present invention, but these corresponding changes and modifications should all fall within the scope of protection of the claims attached to the present invention.

Claims

1. A microneedle patch, characterized in that: It comprises a microneedle layer and a carrier layer, wherein: The microneedle layer includes a base layer and a plurality of microneedles, wherein the microneedles are formed by a solution containing pectin and hyaluronic acid and are spaced apart from each other on the base layer; and The base layer has a first surface and a second surface opposite to each other, wherein the microneedles are located on the first surface, and the microneedle layer is arranged on the carrier layer via the second surface of the base layer.

2. The microneedle patch according to claim 1, characterized in that The weight ratio of pectin to hyaluronic acid in the solution is 0.3-1.

3. The microneedle patch according to claim 2, characterized in that: The weight ratio of pectin to hyaluronic acid in the solution is 0.3 to 0.

7.

4. The microneedle patch according to claim 1, characterized in that The sum of the pectin content and the hyaluronic acid content of the solution accounts for 1 to 2 wt % of the solution.

5. The microneedle patch according to claim 1, characterized in that The hyaluronic acid molecular weight of the solution is less than or equal to 800,000 Da.

6. The microneedle patch according to claim 5, characterized in that The hyaluronic acid molecular weight of the solution further ranges from 3,000 to 800,000 Da.

7. The microneedle patch according to claim 5, characterized in that The base layer is formed by the solution containing pectin and hyaluronic acid, and the microneedle layer is further integrally formed by the solution containing pectin and hyaluronic acid.

8. The microneedle patch according to claim 1, characterized in that The microneedles further contain bioactive ingredients, active pharmaceutical ingredients or a combination thereof.

9. A percutaneous absorption composition, characterized in that: It contains pectin and hyaluronic acid, and the sum of the pectin content and the hyaluronic acid content accounts for 1-2 wt% of the percutaneous absorption composition, and the weight ratio of pectin to hyaluronic acid is 0.3-1.

10. The percutaneous absorption composition according to claim 9, wherein Further comprising biologically active ingredients, active pharmaceutical ingredients or a combination thereof.

11. A soluble film, characterized in that: Prepared from the percutaneous absorption composition according to any one of claims 9 to 10.

12. The soluble film according to claim 11, wherein The invention further comprises a base layer and a plurality of microneedles, wherein the microneedles are arranged on the base layer at intervals.

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