Microneedle patch

Abstract

A microneedle patch comprises a microneedle film and a carrier layer. The microneedle film includes a base layer and a plurality of microneedles, and the microneedle film is formed of at least a film-forming material and a water-soluble material. The plurality of microneedles are spaced apart from each other on the base layer, a molecular weight of the film-forming material is greater than

Description

Technical Field

[0001] This invention relates to the field of transdermal drug delivery, and more particularly to a microneedle patch. Prior Technology

[0002] Microneedle patches (MNPs) are a novel transdermal drug delivery system (TDDS). The microneedles on the patch are very short and do not touch nerves, eliminating the pain associated with subcutaneous injections. They can also carry bioactive ingredients or drugs across the stratum corneum into the body. MNP technology can be used in various fields such as aesthetic medicine, pharmaceuticals, and preventative medicine. Summary of the Invention

[0003] This invention provides a microneedle patch that helps improve defects in the manufacturing process and increases yield and production rate.

[0004] To achieve one, some, or all of the above-mentioned objectives, or other objectives, an embodiment of the present invention provides a microneedle patch comprising a microneedle membrane and a carrier layer. The microneedle membrane includes a substrate layer and a plurality of microneedles, and the microneedle membrane is formed of at least a film-forming material and a water-soluble material. The plurality of microneedles are disposed at intervals on the substrate layer, wherein the molecular weight of the film-forming material is greater than 100,000 Da, the molecular weight of the water-soluble material is not greater than 100,000 Da, and the weight ratio of the film-forming material to the water-soluble material is 2:1 to 4:5. The substrate layer has opposing first and second surfaces, wherein the plurality of microneedles are located on the first surface, and the microneedle membrane is disposed on the carrier layer with the second surface of the substrate layer.

[0005] In one embodiment of the present invention, the microneedle membrane is further formed of at least a film-forming material, a water-soluble material, and a hardening material, wherein the molecular weight of the hardening material is less than 100,000 Da.

[0006] Because this invention uses film-forming materials and water-soluble materials to form microneedle films, it is easy to fill and completely remove bubbles during preparation, which can improve the situation of empty needles, residual bubbles, voids, etc., and form microneedles with complete structure and good puncture function, thereby improving the yield and production rate of microneedle patches.

[0007] To make the above and other objects, features and advantages of the present invention more apparent and understandable, specific embodiments are described below in conjunction with the accompanying drawings for detailed explanation. Simple Explanation of the Diagram

[0008] Figure 1 is a cross-sectional schematic diagram of a microneedle patch according to an embodiment of the present invention. Figure 2 is a schematic diagram of the hourly dissolution rate of microneedles in the embodiments and comparative examples of the present invention. Implementation

[0009] The foregoing descriptions and other technical contents, features, and effects of this invention will be clearly presented in the following detailed description of a preferred embodiment with reference to the accompanying drawings. The directional terms mentioned in the following embodiments are only for reference to the directions in the accompanying drawings. Therefore, the directional terms used are for illustrative purposes and not for limiting the invention. Furthermore, the terms "first," "second," etc., mentioned in this specification or the claims are only used to name elements or distinguish different embodiments or scopes, and are not used to limit the upper or lower limit of the number of elements.

[0010] This invention provides a microneedle patch that can improve manufacturing processes, increasing yield and production efficiency. The microneedle patch provided by this invention, through microneedle puncture, can be used for transdermal drug delivery and absorption, serving as a carrier for several active ingredients and helping to improve their delivery and absorption efficiency. The active ingredients include bioactive components, pharmaceutical ingredients, or combinations thereof. In this invention, a bioactive component means a component that can produce biological effects on humans or other organisms, such as altering human physiological functions and biochemical metabolism. Bioactive components are not limited to achieving therapeutic or preventative effects; however, bioactive components with therapeutic or preventative effects can be equivalent to pharmaceutical ingredients.

[0011] Figure 1 is a cross-sectional schematic diagram of a microneedle patch according to an embodiment of the present invention. As shown in Figure 1, the microneedle patch 1 includes a microneedle film 10 and a carrier layer 20. The microneedle film 10 includes a substrate layer 150 and a plurality of microneedles 100, which are spaced apart from each other on the same side of the substrate layer 150. The diameter of the microneedles 100 increases as they approach the substrate layer 150; specifically, their shape can be, for example, a pyramid or a cone. The length of the microneedles 100 can be 100~1500 μm, for example, 100 μm, 500 μm, 800 μm, 1000 μm, or 1500 μm. The substrate layer 150 has an appropriate thickness, for example, 5~50 μm, and has a first surface 151 and a second surface 152 facing each other. The microneedles 100 are all disposed on the same surface, for example, the first surface 151, while the other surface, such as the second surface 152, can be used to connect the microneedle film 10 to the carrier layer 20. The carrier layer 20 can be used to carry, support, and protect the microneedle membrane 10. Its material can be, for example, a natural or synthetic fabric such as cloth, or a natural or synthetic polymer such as film. The carrier layer 20 can also be used to further fix the microneedle membrane 10 to the epidermis during transdermal delivery. Therefore, its material can also be selected based on several functional requirements such as waterproof, breathable, antibacterial, odor, aesthetics, and feel.

[0012] In this embodiment of the invention, the microneedle membrane 10 is formed from at least a film-forming material and a water-soluble material. The film-forming material is the material used to form the microneedle membrane 10 and is biocompatible. Biocompatibility means that the material should not release toxic or harmful substances that cause local or systemic adverse reactions in the human body or other organisms, such as inflammatory reactions, immune reactions, or toxic reactions. For example, film-forming materials include hyaluronic acid, polyvinylpyrrolidone, polyvinyl alcohol, polylactic acid, chitosan, carboxymethyl cellulose, and chondroitin sulfate, but are not limited thereto. The film-forming material of this embodiment of the invention further has degradability (or solubility). When the microneedle membrane 10 formed with the film-forming material and its microneedles 100 are delivered percutaneously, the microneedles 100 can degrade (or dissolve) over time without causing adverse reactions in the human body or other organisms.

[0013] The film-forming material of this invention has a relatively high molecular weight. Furthermore, polymeric materials can be used as film-forming materials. The film-forming material may have a molecular weight greater than 100,000 Da and can form a polymer. In this document, molecular weight refers to relative molecular mass, but may further be weight average molecular weight (Mw). The weight average molecular weight of the film-forming material is further greater than 100,000 Da to 20,000,000 Da, such as 150,000 Da, 200,000 Da, 300,000 Da, 400,000 Da, 500,000 Da, 600,000 Da, 700,000 Da, 800,000 Da, 900,000 Da, 1,000,000 Da, 2,000,000 Da, 3,000,000 Da, 4,000,000 Da, 5,000,000 Da, 6,000,000 Da, 7,000,000 Da, 8,000,000 Da, 9,000,000 Da, 10,000,000 Da, 15,000,000 Da, 20,000,000 Da. The film-forming material can be formulated with a water-soluble material to form a mixed solution containing both, such as a film-forming solution (hereinafter referred to as the solution) containing the film-forming material and the water-soluble material formulated with an aqueous solvent. The aqueous solvent can be, for example, water. The film-forming solution can be formed into a microneedle membrane 10 through steps including injection molding (injection into a mold) and drying.

[0014] The molecular weight of the water-soluble material in the microneedle membrane 10 is smaller than that of the film-forming material. The water-soluble material is also a bioactive, pharmaceutical, or combination thereof. In other words, the water-soluble material is further a bioactive component, pharmaceutical component, or combination thereof, as described above, i.e., an active ingredient. The water-soluble material, as an active ingredient, is carried on the microneedle membrane 10 and microneedles 100 and can be delivered transdermally to the human body or other organisms. Furthermore, the water-soluble material can be degraded within the microneedles 100 and exert its effects within the body.

[0015] The water-soluble material of the present invention may have a molecular weight of less than or equal to 100,000 Da, and further from 500 Da to 100,000 Da, for example 500 Da, 1000 Da, 2,000 Da, 3,000 Da, 4,000 Da, 5,000 Da, 6,000 Da, 7,000 Da, 8,000 Da, 9,000 Da, 10,000 Da, 20,000 Da, 30,000 Da, 40,000 Da, 50,000 Da, 60,000 Da, 70,000 Da, 80,000 Da, 90,000 Da, and 100,000 Da. The molecular weight of the water-soluble material can further be 500 Da to 10,000 Da, such as 500 Da, 1000 Da, 1,500 Da, 2,000 Da, 2,500 Da, 3,000 Da, 3,500 Da, 4,000 Da, 4,500 Da, 5,000 Da, 5,500 Da, 6,000 Da, 6,500 Da Da, 7,000 Da, 7,500 Da, 8,000 Da, 8,500 Da, 9,000 Da, 9,500 Da, 10,000 Da.

[0016] Specifically, water-soluble materials may include organic compounds, inorganic compounds, extracts, or combinations thereof. The organic and inorganic compounds and extracts (e.g., extracts from organisms) may be natural or synthetic, and preferably possess biological activity, pharmaceutical properties, or combinations thereof. For example, water-soluble materials may be, but are not limited to, proteins, peptides, amino acids, other organic acids or their derivatives, polysaccharides or their derivatives, vitamins, alcohols, amines, amides, drugs, or combinations thereof. Water-soluble materials are not limited to one type; that is, multiple water-soluble materials may be used in combination for the microneedle membrane 10. In embodiments of the present invention, water-soluble materials may be, for example, proteins such as collagen, peptides such as collagen peptides, and other compounds with effects such as anti-wrinkle, anti-aging, moisturizing, or combinations thereof.

[0017] In addition to being an effective component, water-soluble materials, when combined with film-forming materials, can optimize the manufacturing process and improve the yield of microneedle film 10. Specifically, when forming microneedle film 10 using film-forming materials and water-soluble materials, an appropriate proportion of water-soluble materials helps to mitigate the high viscosity of the film-forming solution caused by the film-forming material. Furthermore, the film-forming solution undergoes steps including molding (filling the mold with the solution) and degassing when forming microneedle film 10. The viscosity of the film-forming solution affects the ease of filling and the effectiveness of degassing, thus affecting the forming and production yield of microneedle film 10. Because water-soluble materials can lower the viscosity of the film-forming solution, an appropriate proportion of water-soluble materials can reduce the solution viscosity sufficiently, making filling easier and facilitating smooth degassing and effective removal of air bubbles from the solution. Conversely, if the content of water-soluble materials is not in an appropriate proportion, it will be difficult to effectively improve filling and degassing issues. Incomplete filling, degassing issues, and failure to remove air bubbles can lead to incomplete microneedle membrane 10 structure, poor microneedle membrane 10 formation, and failure to form microneedle membrane 10, such as empty needles, residual bubbles, and voids.

[0018] However, it should be noted that if the content of the water-soluble solution exceeds the aforementioned appropriate ratio, while the content of the film-forming material is relatively insufficient, it can easily lead to a decrease in the strength of the microneedle membrane 10, resulting in situations such as the microneedles 100 becoming brittle and easily broken, and the substrate layer 150 becoming brittle. The appropriate ratio of the water-soluble material can be expressed, for example, as a weight percentage or weight ratio. In the embodiments of the present invention, the weight ratio of the film-forming material to the water-soluble material can be 2:1 to 4:5, for example, 2:1, 6:5, 5:4, 1:1, 8:9, or 4:5.

[0019] In addition, other functional ingredients may be added to the film-forming solution to give the formed microneedle membrane additional or enhanced effects. These functional ingredients may include, but are not limited to, proteins, peptides, amino acids, other organic acids or their derivatives, polysaccharides or their derivatives, vitamins, alcohols, amines, acetamides, drugs, or combinations thereof. Examples of functional ingredients include, for instance, ergothioneine, tranexamic acid, salicylic acid, ceramides, nicotinamides, B vitamins, vitamin C, Ganoderma lucidum polysaccharides, Astragalus polysaccharides, Polygonatum odoratum polysaccharides, Rehmannia glutinosa polysaccharides, and certain drugs. The effects of these functional ingredients may include, but are not limited to, whitening, anti-aging, anti-acne, antioxidant, anti-inflammatory, maintaining or enhancing immune system function, analgesia, sedation, antipyresis, or combinations thereof.

[0020] The microneedle membrane 10 of this embodiment is further formed from the aforementioned film-forming material, water-soluble material, and film-hardening material. The film-hardening material can be used to adjust the film-forming properties, and preferably to improve the extensibility, softness, and elasticity of the microneedle membrane 10. For example, the film-hardening material can be embedded between the molecular chains of the polymer formed by the film-forming material, thereby reducing the attraction between the polymer molecular chains, increasing the molecular chain mobility and fluidity, and thus achieving the effect of improved extensibility, softness, and elasticity.

[0021] The membrane-forming material may have a relatively small molecular weight. In embodiments of the invention, the molecular weight of the membrane-forming material may be smaller than that of the film-forming material, for example, less than 100,000 Da, but is not limited thereto. The molecular weight of the membrane-forming material is generally smaller than that of the water-soluble material, but is not limited thereto. Specifically, the membrane-forming material may include monosaccharides, disaccharides, oligosaccharides, polyols, lipids or their derivatives or combinations thereof. The membrane-forming material is not limited to one type; that is, multiple membrane-forming materials may be used in combination for the microneedle membrane 10. The molecular weight of the membrane-forming material may further be, for example, less than 500 Da, but is not limited thereto. In embodiments of the invention, the membrane-forming material may include, for example, fructose, glucose, trehalose, honey, glycerol, sorbitol, xylitol, maltitol, diglycerol, and dipropylene glycol.

[0022] Plasticizers, humectants, and certain polymeric compounds can also be used as film-forming materials, such as polyethylene glycol and polyglutamic acid. In several embodiments of the present invention, the molecular weight of the polyglutamic acid used can be high, for example, over ten million, or low, in the millions. For example, the molecular weight range of polyglutamic acid can be 10,000,000 Da to 12,000,000 Da or 2,000,000 Da to 4,000,000 Da.

[0023] Besides adjusting film-forming properties, the amount of water-soluble material can be further increased by adding the film-forming material. This, on the one hand, gives the microneedle membrane 10 extensibility, softness, and elasticity, improving its original brittle and easily broken properties; on the other hand, it increases the content of effective ingredients within the microneedle membrane 10, and also helps to make filling easier and defoaming more effective. The aforementioned weight ratio of film-forming material to water-soluble material of 2:1 to 4:5 is preferably an appropriate ratio given the presence of film-forming material. In embodiments of the present invention, the weight ratio of film-forming material to water-soluble material and to film-forming material is 9.5:0.5 to 8:2, for example, 9.5:0.5, 9:1, 8.8:1.2, 8.5:1.5, 8.2:1.8, and 8:2. Furthermore, when the hardening material also has the properties of a water-soluble material, the hardening material can be equivalent to a water-soluble material and used as such. The ratio of the film-forming material to the hardening material (water-soluble material) is preferably 2:1 to 4:5. Moreover, the ratio of the sum of the film-forming material and the hardening material (water-soluble material) to the hardening material (water-soluble material) is preferably 9.5:0.5 to 8:2.

[0024] For specific examples of film-forming materials, water-soluble materials, and hard film materials, please refer to Examples 1 and 2.

[0025] Example 1: Example 1 uses 200,000 Da hyaluronic acid as the film-forming material and trehalose (below 500 Da) as the film-forming material. The water-soluble material is 3,000 Da hydrolyzed collagen. The weight ratios of hyaluronic acid (200,000 Da), hydrolyzed collagen, and trehalose are shown in Table 1 below. Examples 1-1 to 1-5 do not use film-forming materials. Examples 1-1 to 1-8 are prepared into film solutions, and then subjected to steps such as injection (filling), degassing, and drying to form the film. Table 1 Hyaluronic acid (parts by weight) Hydrolyzed collagen (parts by weight) Trehalose (parts by weight) Poor foam removal Membrane surface brittleness determination 1-1 9 1 0 have none NG 1-2 8 2 0 have none NG 1-3 7 3 0 have have NG 1-4 6 4 0 none have NG 1-5 5 5 0 none have NG 1-6 6 3 1 none none OK 1-7 4.8 4 1.2 none none OK 1-8 4 4.5 1.5 none none OK As seen in 1-1 to 1-5, the problem of poor foaming is improved with the increase of hydrolyzed collagen content; however, the problem of membrane brittleness also occurs. Specifically, when the weight ratio of hyaluronic acid to hydrolyzed collagen reaches 6:4, the problem of poor foaming is resolved, but membrane brittleness occurs. As seen in 1-6 to 1-8, the addition of trehalose resolves both the problems of poor foaming and membrane brittleness. Specifically, when the weight ratio of hyaluronic acid to hydrolyzed collagen reaches approximately 4.8:4 (example 1-7), close to 1:1, and even further increases in the hydrolyzed collagen content to exceed that of hyaluronic acid (example 1-8), membrane brittleness does not occur. In contrast, as shown in example 1-5, without trehalose, if the amount of hydrolyzed collagen is increased to be equivalent to that of hyaluronic acid (5:5), the microneedle membrane 10 exhibits poor formation.

[0026] Example 2: Example 2 uses 850,000 Da hyaluronic acid as the film-forming material and polyglutamic acid as the film-hardening material. The water-soluble material is 500 Da collagen peptides. The weight ratios of hyaluronic acid (850,000 Da), collagen peptides, and polyglutamic acid are shown in Table 2 below. Examples 2-1 to 2-5 do not use film-hardening materials. Examples 2-1 to 2-8 are prepared into film solutions, and then subjected to steps such as injection (filling), degassing, and drying to form the film. Table 2 Hyaluronic acid (parts by weight) Collagen peptides (parts by weight) polyglutamic acid (parts by weight) Poor foam removal Membrane surface brittleness determination 2-1 9 1 0 have none NG 2-2 8 2 0 have none NG 2-3 7 3 0 have have NG 2-4 6 4 0 none have NG 2-5 5 5 0 none have NG 2-6 6 3 1 none none OK 2-7 5 4 1 none none OK 2-8 4 5 1 none none OK As seen in Figures 2-1 to 2-5, the problem of poor foam drainage is improved with the increase of collagen peptide content; however, the problem of membrane brittleness also occurs. Specifically, when the weight ratio of hyaluronic acid to collagen peptides reaches 6:4, the problem of poor foam drainage is resolved, but membrane brittleness occurs. As seen in Figures 2-6 to 2-8, the addition of polyglutamic acid resolves both the problems of poor foam drainage and membrane brittleness. Specifically, when the weight ratio of hyaluronic acid to collagen peptides reaches a ratio close to 1:1 (5:4, as shown in Figure 2-7), and even further increases the collagen peptide content to exceed that of hyaluronic acid (as shown in Figure 2-8), membrane brittleness does not occur. In contrast, as shown in Figure 2-5, without polyglutamic acid, it is impossible to increase the amount of collagen peptides to be equivalent to that of hyaluronic acid (5:5), resulting in poor microneedle membrane 10 formation.

[0027] In summary, the microneedle membrane 10 of this invention has good molding properties and possesses extensibility, softness, and elasticity, without problems such as brittleness and breakage, and the amount of water-soluble material it contains can be increased. Therefore, the microneedle 100 of this invention can effectively puncture the skin, has high delivery efficiency, and allows the active ingredients to exert their effects more effectively. The microneedle membrane 10 of this invention can also be used to further accelerate the release of active ingredients, achieving the desired effect in a shorter time.

[0028] Figure 2 is a schematic diagram of the hourly dissolution rate of the microneedle patch 1 of the embodiment of the present invention and the microneedle patch of the comparative example. The microneedle patch 1 of the embodiment of the present invention in Figure 2 has a microneedle film 10 formed by a film-forming material, a water-soluble material, and a film-hardening material, wherein the weight ratio of the film-forming material to the water-soluble material is in the range of 2:1 to 4:5, and the weight ratio of the film-forming material to the water-soluble material and to the film-hardening material is in the range of 9.5:0.5 to 8:2, while the microneedle film of the comparative example is formed only by the film-forming material. The dissolution rate can be calculated as the percentage of the weight of the multiple microneedles dissolved on the microneedle film to the total weight of the microneedles in the microneedle film. As shown in Figure 2, the degradation of the embodiment of the present invention can be accelerated due to the relatively low amount of film-forming material. For example, the dissolution rate of the microneedles 100 can be greater than 50% (e.g., 62.3%) within one hour (60 min), while the dissolution rate of the comparative example is less than 20% within one hour. Furthermore, the needle dissolution rate of the embodiments of the present invention shows a generally positive linear correlation with time, reflecting that the needle dissolution rate can steadily increase over time. In the comparative example, the needle dissolution rate after one hour was only about 2% higher than that after half an hour (30 min). Based on this, the microneedle patch 1 of the embodiments of the present invention can also be used for active ingredients with short-release requirements, and has the effect of stable and continuous release within a specific time. On the other hand, the amount of water-soluble material is also increased, so the microneedle patch 1 of the embodiments of the present invention also helps to achieve significant ingredient effects in a shorter time.

[0029] Although the present invention has been disclosed above by way of embodiments, it is not intended to limit the present invention. Those skilled in the art to which this invention pertains may make some modifications and refinements without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

[0030] 1: Microneedle patch 10: Microneedle membrane 100: Microneedles 150: Basal layer 151: First Page 152: Second page 20: Carrier layer

Claims

1. A microneedle patch comprising a microneedle membrane and a carrier layer, wherein: The microneedle membrane includes a base layer and a plurality of microneedles, and the microneedle membrane is formed of at least a film-forming material and a water-soluble material; wherein the plurality of microneedles are disposed at intervals on the base layer, and the molecular weight of the film-forming material is greater than 100,000 Da, the molecular weight of the water-soluble material is not greater than 100,000 Da, and the weight ratio of the film-forming material to the water-soluble material is 2:1 to 4:5; and the base layer has a first side and a second side opposite to each other, wherein the plurality of microneedles are located on the first side, and the microneedle membrane is disposed on the carrier layer with the second side of the base layer.

2. The microneedle patch as claimed in claim 1, wherein the molecular weight of the film-forming material is a weight average molecular weight, and the weight average molecular weight of the film-forming material is further greater than 100,000 Da to 20,000,000 Da.

3. The microneedle patch as described in claim 1, wherein the molecular weight of the water-soluble material is further from 500 Da to 100,000 Da.

4. The microneedle patch as described in claim 3, wherein the molecular weight of the water-soluble material is further 500 Da to 10,000 Da.

5. The microneedle patch as described in claim 1, wherein the water-soluble material is further a bioactive ingredient.

6. The microneedle patch as described in claim 1, wherein the microneedle membrane further comprises an efficacy ingredient.

7. The microneedle patch as described in claim 5, wherein the water-soluble material comprises natural or synthetic organic compounds, natural or synthetic inorganic compounds, extracts, or combinations thereof.

8. The microneedle patch as claimed in claim 3, wherein the microneedle membrane is further formed of at least the film-forming material, the water-soluble material and a hard film material.

9. The microneedle patch as described in claim 8, wherein the molecular weight of the film-forming material is less than the molecular weight of the water-soluble material.

10. The microneedle patch as claimed in claim 8, wherein the weight ratio of the film-forming material and the water-soluble material to the weight of the hardening material is 9.5:0.5 to 8:

2.

11. The microneedle patch as claimed in claim 8, wherein the film-forming material comprises monosaccharides, disaccharides, oligosaccharides, polyols, lipids or derivatives thereof, plasticizers, humectants or combinations thereof.

12. The microneedle patch as described in claim 11, wherein the hard film material is further polyglutamic acid.

13. The microneedle patch as claimed in claim 1, wherein the plurality of microneedles are soluble and the microneedle dissolution rate of the microneedle membrane is greater than 50% in any hour; the microneedle dissolution rate is the percentage of the weight of the dissolved plurality of microneedles to the total weight of the plurality of microneedles in the microneedle membrane.

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