Magnetophoretic transdermal delivery hydrogel microneedle device

Abstract

The invention relates to a magnetophoretic transdermal delivery hydrogel microneedle device, which belongs to the technical field of medicine, and comprises a base layer, a plurality of hydrogel microneedles are arranged on one side of the base layer at equal intervals along the length and width directions of the base layer, each hydrogel microneedle is composed of a methyl vinyl ether-maleic acid copolymer and pectin, a medicine layer is arranged on the other side of the base layer, and the hydrogel microneedles are arranged on the other side of the medicine layer. The hydrogel microneedle penetrates through the skin surface layer to form a drug delivery channel, the hydrogel microneedle composed of the methyl vinyl ether-maleic acid copolymer and the pectin has high mechanical strength and toughness, the situation that the hydrogel microneedle breaks during puncture is reduced, and the drug delivery effect is improved. The broken micro-needle fragments can be naturally decomposed, local infection and inflammatory reaction caused by long-time residual of the micro-needle fragments in the skin are avoided, extra risks caused by treatment are reduced, the magnetic layer drives the diamagnetic medicine to enter the skin along the administration channel through magnetomotive force, and therefore the medicine release efficiency of the hydrogel micro-needle is improved.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular relates to a magnetophoretic transdermal drug delivery hydrogel microneedle device. Background Art

[0002] Due to factors such as the aging population, lack of exercise, and obesity, joint diseases have become increasingly common in recent years. Joint diseases not only bring physical pain, but also affect patients' daily lives and overall health in many ways. Common joint diseases include rheumatoid arthritis, osteoarthritis, gout, etc., and the medication methods include oral, intravenous, local injection, and topical therapy. Among them, oral and intravenous injections not only have poor targeting, resulting in low drug concentrations at the lesion site, but may also have side effects on organs such as the gastrointestinal tract, liver, and kidneys. Therefore, the main medication methods for joint diseases are local injection or topical therapy, which can deliver drugs directly to the lesion site, thereby achieving higher local drug concentrations and reducing systemic side effects. However, local injections are often accompanied by obvious pain, which affects patients' treatment experience and compliance. Topical therapy reduces the drug penetration effect due to the natural barrier effect of the skin epidermis, making it difficult for drugs to effectively penetrate into the subcutaneous tissue, thereby reducing the therapeutic effect of joint diseases.

[0003] In order to improve the effect of medication for joint diseases, micro needle tips are generally used for drug delivery. The size of the micro needle tips is small, and the length is controlled below 1 mm. It can build a drug delivery pathway within a certain period of time, cross the epidermal defense line, and guide the drug to the subcutaneous tissue or directly into the blood circulation. Depending on the specific application scenario, the micro needle tip device has a variety of mounting forms, including pen type, rolling wheel type, and patch type. However, the material of the existing micro needle tips is metal or silicon. Although it has a certain mechanical strength, it lacks toughness. The micro needle tip is prone to breakage during the puncture process, and the broken micro needle fragments remain in the skin and cannot be naturally decomposed. Since the micro needle fragments are very small and difficult to remove, if they remain for a long time, they will cause local infection and inflammatory reactions, resulting in hidden dangers in the diagnosis and treatment process.

[0004] At present, in order to avoid hidden dangers caused by micro needle tips during drug delivery, hydrogel microneedles are often used for drug delivery. After penetrating the surface layer of the skin, the hydrogel microneedles absorb interstitial fluid to expand and form holes, and the drug components carried are released through the holes. The hydrogel microneedles have biocompatibility and biodegradability, so that the broken microneedle fragments can be naturally decomposed, thereby reducing the risk of treatment. However, when the hydrogel microneedle breaks, although it can be naturally degraded, it will reduce the drug delivery efficiency. In addition, the speed at which the hydrogel microneedle releases the drug depends on the speed of absorbing interstitial fluid to form holes, resulting in the problem of low drug release efficiency of the hydrogel microneedle. In the prior art, shock waves, heating and electroosmosis are often used to speed up the drug delivery speed, but the above-mentioned drug delivery methods have problems such as cumbersome operation methods. Summary of the invention

[0005] In view of this, the present invention provides a magnetophoretic transdermal drug delivery hydrogel microneedle device to address the deficiencies in the prior art. The present invention can reduce the additional risks brought by treatment and improve the drug release efficiency of the hydrogel microneedle.

[0006] The technical solution of the present invention is: a magnetophoretic transdermal drug delivery hydrogel microneedle device, comprising a base layer, a plurality of hydrogel microneedles are arranged at equal intervals along the length and width directions of the base layer on one side thereof, and are perpendicular to the base layer, the tail of the hydrogel microneedle is fixedly connected to the base layer, the hydrogel microneedle is composed of methyl vinyl ether-maleic acid copolymer and pectin, the hydrogel microneedle penetrates the surface layer of the skin to form a drug delivery channel, the drug layer is arranged on the other side of the base layer, the drug layer is fixedly connected to the base layer, and the magnetic layer is arranged on the side of the drug layer away from the base layer, and the magnetic layer is fixedly connected to the drug layer to drive the drug into the skin through the drug delivery channel.

[0007] Preferably, the ratio of methyl vinyl ether-maleic acid copolymer to pectin is in the range of 10-15:4.

[0008] Preferably, the magnetic layer comprises: PVP: 10-30wt%, NdFeB magnetic powder: 42-54wt%, ferrite magnetic powder: 28-36wt%, and lubricant: 0-3wt%.

[0009] Preferably, the method further comprises: a backing layer, which is arranged on a side of the magnetic layer away from the drug layer, and the area of ​​the backing layer is larger than the areas of the drug layer and the magnetic layer.

[0010] Preferably, the backing layer is made of any one of spunlace nonwoven fabric, polyurethane film, polyethylene film or other soft medical films that fit the skin.

[0011] Preferably, the method further comprises: a sealing film, which is arranged on a side of the hydrogel microneedle away from the base layer, and the sealing film is detachably connected to the hydrogel microneedle.

[0012] Preferably, the sealing film is made of silicone oil paper.

[0013] Preferably, the diameter of the hydrogel microneedle is 50 to 200 μm, and the height of the hydrogel microneedle is 200 to 800 μm.

[0014] Preferably, the spacing between adjacent hydrogel microneedles is 500-800 μm.

[0015] Compared with the prior art, the present invention provides a magnetophoretic transdermal drug delivery hydrogel microneedle device, which can enable the hydrogel microneedle to penetrate the skin surface to form a drug delivery channel through the coordinated use of a base layer, a hydrogel microneedle, a drug layer and a magnetic layer. The hydrogel microneedle composed of methyl vinyl ether-maleic acid copolymer and pectin has strong mechanical strength and toughness, which can reduce the breakage of the hydrogel microneedle during puncture. The hydrogel microneedle has biocompatibility and biodegradability, and the broken microneedle fragments can decompose naturally, avoiding the microneedle fragments from remaining in the skin for a long time to cause local infection and inflammatory response, thereby reducing the additional risks brought by treatment. At the same time, the magnetic layer uses magnetic power to drive the antimagnetic drug to enter the skin through the drug delivery channel, thereby improving the drug release efficiency of the hydrogel microneedle. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is a schematic diagram of the structure of the hydrogel microneedle device of the present invention.

[0018] Description of reference numerals: 1. Base layer; 2. Hydrogel microneedles; 3. Drug layer; 4. Magnetic layer; 5. Backing layer; 6. Sealing film. DETAILED DESCRIPTION

[0019] The present invention provides a hydrogel microneedle device for transdermal drug delivery by magnetophoresis. Figure 1 The present invention is described with reference to the schematic diagram of FIG.

[0020] In the description of the present invention, it is to be understood that the terms “center”, “longitudinal”, “lateral”, “length”, “width”, “thickness”, “up”, “down”, “front”, “back”, “left”, “right”, “vertical”, “horizontal”, “top”, “bottom”, “inside”, “outside”, “axial”, “radial”, “circumferential”, etc., indicating orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, are only for the convenience of describing the technical solutions of the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0021] Reference Figure 1 , Figure 1Schematic diagram of the structure of the hydrogel microneedle device of this embodiment. Figure 1 As shown, a magnetophoretic transdermal drug delivery hydrogel microneedle device comprises a base layer 1, a plurality of hydrogel microneedles 2 are arranged at equal intervals along the length and width directions of the base layer 1 on one side thereof, and are perpendicular to the base layer 1, the tail of the hydrogel microneedle 2 is fixedly connected to the base layer 1, the hydrogel microneedle 2 is composed of methyl vinyl ether-maleic acid copolymer and pectin, the hydrogel microneedle 2 penetrates the surface layer of the skin to form a drug delivery channel, a drug layer 3 is arranged on the other side of the base layer 1, the drug layer 3 is fixedly connected to the base layer 1, and a magnetic layer 4 is arranged on a side of the drug layer 3 away from the base layer 1, and the magnetic layer 4 is fixedly connected to the drug layer 3 to drive the drug into the skin through the drug delivery channel.

[0022] The embodiment of the present invention provides a hydrogel microneedle device for transdermal drug delivery by magnetophoresis. The base layer, hydrogel microneedle, drug layer and magnetic layer are used in combination to enable the hydrogel microneedle to penetrate the skin surface to form a drug delivery channel. The hydrogel microneedle composed of methyl vinyl ether-maleic acid copolymer and pectin has strong mechanical strength and toughness, which can effectively reduce the occurrence of breakage during puncture. In addition, the hydrogel microneedle has good biocompatibility and biodegradability, and the broken hydrogel microneedle fragments can also be naturally decomposed in the body, avoiding local infection and inflammatory response caused by microneedle fragments being retained in the skin tissue for a long time, reducing the additional risks that may be generated during the treatment process, ensuring the safety and effectiveness of the treatment, and at the same time, with the help of the magnetic power generated by the magnetic layer and the antimagnetic drug, the drug is prompted to penetrate into the deep layer of the skin along the drug delivery channel, thereby improving the release efficiency of the drug in the hydrogel microneedle. The microneedle device of the present invention has good effect, is easy to use, has strong practicality, and is worth promoting.

[0023] The hydrogel microneedle device for magnetophoresis transdermal drug delivery provided in this embodiment can penetrate the stratum corneum of the skin and form micrometer-scale pores. After being inserted into the skin, the hydrogel microneedle 2 will quickly absorb tissue fluid, swell, and transform from a glassy state to a hydrogel state. As a result, the volume of the microneedle gradually increases, and the holes formed can allow the drug in the drug layer 3 on the back of the hydrogel microneedle 2 to diffuse from the microneedle to the skin along the concentration gradient. The magnetic layer 4 makes full use of magnetic power to further promote the antimagnetic drug to pass through the drug delivery channel made by the microneedle, thereby improving the drug delivery efficiency of the magnetophoresis transdermal drug delivery hydrogel microneedle device.

[0024] By creating a drug delivery channel through hydrogel microneedles, drugs can pass through the epidermis of the skin and directly enter the dermis of the skin without piercing the muscles, effectively avoiding pain and improving drug utilization.

[0025] Magnetic field therapy promotes the release of magnetic nanoparticles or antimagnetic drugs through two potential mechanisms: magnetic repulsion and magnetic hydrogen movement. Under the action of the magnetic layer 4, the induced antimagnetic body generates a corresponding repulsive force due to magnetic repulsion, driving the antimagnetic drug molecules to move. The magnetic hydrogen movement mediates drug transport by means of the movement of water through the membrane under the influence of the external magnetic field. Under the guidance of the magnetic layer 4, the drug is delivered to the diseased joint site, the concentration of the drug in the diseased site is increased, and the magnetic field can also be used to promote the penetration of the drug and enhance the therapeutic effect.

[0026] In addition, the magnetic field generated by the magnetic layer 4 can also improve local microcirculation, increase vascular permeability, reduce inflammation, swelling and pain, and promote the body's absorption of drugs, further improving the restorative treatment effect on joint diseases. For example, rheumatoid arthritis can be treated by targeting the affected area with hydrogel microneedles combined with magnetic therapy. On the one hand, magnetophoresis can be used to effectively and accurately introduce the drug components in the drug layer into specific skin parts, and the magnetic therapy effect can be fully utilized to assist in the treatment of rheumatoid arthritis. On the other hand, it can reduce the side effects of dizziness, nausea, etc. caused by large-area magnetic therapy.

[0027] On the other hand, a moderate magnetic field can affect the activity of ion channels in cells, causing changes in the ion concentration inside and outside the cells, thereby regulating physiological processes such as nerve conduction and muscle contraction. For example, it can make the electrical signal transmission of nerve cells more stable and efficient, and maintain good muscle contraction and relaxation functions. On the other hand, the magnetic field also has the ability to promote local blood circulation, by accelerating the delivery of nutrients in the blood and the removal of metabolic waste, creating a good environment for the repair and recovery of damaged tissues and accelerating the healing process.

[0028] Compared with traditional treatments, extracorporeal magnetic phoresis therapy is non-invasive, produces fewer side effects, is relatively inexpensive, and has certain cost-effectiveness advantages.

[0029] In view of the problem that the existing patches have poor drug permeability and insignificant therapeutic effects, the magnetophoretic transdermal drug delivery hydrogel microneedle device of the present invention adopts hydrogel microneedle technology to manufacture a drug delivery channel and improve drug utilization.

[0030] In view of the low toughness and non-degradability of microneedle materials, the magnetophoretic transdermal drug delivery hydrogel microneedle device of the present invention uses biocompatible and biodegradable hydrogel microneedles, which can effectively reduce the additional risks brought by treatment.

[0031] The existing hydrogel microneedle technology has the problem of low drug release efficiency. The drug delivery speed is mainly accelerated by shock waves, heating and electroosmosis. However, the above-mentioned drug delivery methods have problems such as cumbersome operation methods. In order to improve the drug release efficiency of hydrogel microneedles and increase convenience, the magnetophoretic transdermal drug delivery hydrogel microneedle device of the present invention adopts a magnetophoretic drug delivery method.

[0032] The drug layer 3 in this embodiment is prepared by mixing a cross-linked polymethyl vinyl ether-maleic acid copolymer (PMVE / MA) and pectin (PE) with an appropriate amount of drug, which is then uniformly poured into a mold for drying and solidification, and then the polymer film is peeled off from the mold to obtain the drug layer 3. The drug loading capacity can be effectively increased by using the drug layer 3, which can break through the limitation of the small drug loading capacity of the microneedles, thereby enhancing the therapeutic effect and improving convenience.

[0033] As a further optimization scheme, in this embodiment, the ratio of methyl vinyl ether-maleic acid copolymer to pectin is in the range of 10-15:4.

[0034] The hydrogel microneedles in this embodiment are made of methyl vinyl ether-maleic acid copolymer (PMVE / MA) and pectin (PE) in a ratio range of 10-15:4, so that the hydrogel microneedles have high mechanical strength, anti-dissolution and fast swelling rate, which is beneficial for drug delivery.

[0035] The hydrogel microneedles in this embodiment are made of methyl vinyl ether-maleic acid copolymer (PMVE / MA) and pectin (PE) in a ratio of 10:4.

[0036] The hydrogel microneedles in this embodiment are made of methyl vinyl ether-maleic acid copolymer (PMVE / MA) and pectin (PE) in a ratio range of 13:4.

[0037] The hydrogel microneedles in this embodiment are made of methyl vinyl ether-maleic acid copolymer (PMVE / MA) and pectin (PE) in a ratio of 15:4.

[0038] As a further optimization solution, the magnetic layer 4 in this embodiment includes: PVP: 10-30 wt%, NdFeB magnetic powder: 42-54 wt%, ferrite magnetic powder: 28-36 wt%, and lubricant: 0-3 wt%.

[0039] The magnetic layer 4 in this embodiment is composed of PVP, NdFeB magnetic powder, ferrite magnetic powder and lubricant, so that the magnetic layer 4 has good magnetic properties, and the generated bioresponsive magnetic field has better effect, thereby improving drug administration efficiency and magnetic therapy effect.

[0040] In this embodiment, 30wt% PVP, 42wt% NdFeB magnetic powder and 28wt% ferrite magnetic powder are uniformly stirred and cast in a mold, and the solvent is waited for evaporation and dried to obtain a soft magnetic sheet with a thickness of 0.2mm. The thickness of the magnetic layer 4 is 0.2mm.

[0041] In this embodiment, PVP: 20wt%, NdFeB magnetic powder: 46wt%, ferrite magnetic powder: 32wt%, and lubricant: 2wt% are uniformly stirred and cast into a mold, and the solvent is waited for to evaporate and dried to obtain a soft magnetic sheet. The thickness of the soft magnetic sheet is 0.4mm, and the thickness of the magnetic layer 4 is 0.4mm.

[0042] In this embodiment, PVP: 10wt%, NdFeB magnetic powder: 52wt%, ferrite magnetic powder: 35wt%, and lubricant: 3wt% are uniformly stirred and cast into a mold, and the solvent is waited for to evaporate and dried to obtain a soft magnetic sheet. The thickness of the soft magnetic sheet is 0.6mm, and the thickness of the magnetic layer 4 is 0.6mm.

[0043] In this embodiment, PVP: 10wt%, NdFeB magnetic powder: 54wt%, and ferrite magnetic powder: 36wt% are uniformly stirred and cast in a mold, and the solvent is waited for to evaporate and dried to obtain a soft magnetic sheet. The thickness of the soft magnetic sheet is 1.0mm, and the thickness of the magnetic layer 4 is 1.0mm.

[0044] As a further optimization solution, this embodiment also includes: a backing layer 5 , which is arranged on the side of the magnetic layer 4 away from the drug layer 3 , and the area of ​​the backing layer 5 is larger than the areas of the drug layer 3 and the magnetic layer 4 .

[0045] In this embodiment, the outer edge portion of the backing layer 5 which is larger than the magnetic layer 4 is adhered to the skin, thereby fixing the entire magnetophoretic transdermal drug delivery hydrogel microneedle device.

[0046] As a further optimization solution, the backing layer 5 in this embodiment is made of any one of spunlace non-woven fabrics, polyurethane film, polyethylene film or other soft medical films that fit the skin.

[0047] In this embodiment, the backing layer 5 is made of non-spunlace non-woven fabric: it has good air permeability and softness and is low in cost, and is suitable for large-scale applications.

[0048] In this embodiment, the backing layer 5 is made of polyurethane film: it has high biocompatibility to reduce the probability of allergies, excellent mechanical properties, high strength and elasticity, and strong plasticity, and can meet different design requirements.

[0049] In this embodiment, the backing layer 5 is made of polyethylene film: it has good waterproof performance, can protect the active ingredients in the hydrogel microneedles, prevent the drugs from being diluted by external moisture, and ensure the stability and effectiveness of the drugs.

[0050] As a further optimization solution, this embodiment also includes: a sealing film 6, which is arranged on a side of the hydrogel microneedle 2 away from the base layer 1, and the sealing film 6 is detachably connected to the hydrogel microneedle 2.

[0051] In this embodiment, the sealing film 6 has a moisture-proof effect to prevent the hydrogel microneedles from absorbing water and swelling.

[0052] In this embodiment, the sealing film is peelably arranged at the end of the hydrogel microneedle, the sealing film and the backing layer have equal areas, the magnetic layer and the drug layer have equal areas, and the backing layer has a larger area than the magnetic layer.

[0053] As a further optimization solution, the material of the sealing film 6 in this embodiment is silicone oil paper.

[0054] In this embodiment, the surface of the silicone oil paper used in the sealing film 6 is coated with a silicone coating, which is not easy to stick to the hydrogel microneedles when in contact with them, thereby avoiding deformation or damage of the hydrogel microneedles due to tearing off the sealing film. Compared with plastic sealing films, paper-based materials are easier to degrade naturally and do not contain plasticizers, which is more in line with the safety standards of medical supplies.

[0055] In this embodiment, the silicone oil paper is cut into a suitable size, and the cut silicone oil paper is placed on the hydrogel microneedle, and light pressure is applied to make the silicone oil paper and the hydrogel microneedle fit better, ensuring that the silicone oil paper and the hydrogel microneedle fit completely. However, be careful not to use excessive force to avoid damaging the hydrogel microneedle, and then the edges of the silicone oil paper are bonded and connected to the base layer.

[0056] As a further optimization solution, the diameter of the hydrogel microneedle 2 is 50 to 200 μm, and the height of the hydrogel microneedle 2 is 200 to 800 μm.

[0057] As a further optimization scheme, the spacing between adjacent hydrogel microneedles 2 is 500-800 μm, and the size of the hydrogel microneedle 2 on the base layer is 1*1 cm 2 ~2.5*2.5cm 2 .

[0058] The above disclosure is only a preferred specific embodiment of the present invention, but the embodiments of the present invention are not limited thereto, and any changes that can be conceived by those skilled in the art should fall within the protection scope of the present invention.

Claims

1. A hydrogel microneedle device for magnetophoretic transdermal drug delivery, characterized in that: include: Base layer (1); A plurality of hydrogel microneedles (2) are arranged at equal intervals on one side of the base layer (1) along the length and width directions thereof and are perpendicular to the base layer (1); the tails of the hydrogel microneedles (2) are fixedly connected to the base layer (1); the hydrogel microneedles (2) are composed of methyl vinyl ether-maleic acid copolymer and pectin; and the hydrogel microneedles (2) penetrate the surface layer of the skin to form a drug delivery channel; A drug layer (3) is arranged on the other side of the base layer (1), and the drug layer (3) is fixedly connected to the base layer (1); The magnetic layer (4) is arranged on a side of the drug layer (3) away from the base layer (1), and the magnetic layer (4) is fixedly connected to the drug layer (3) to drive the drug to enter the skin through the drug delivery channel.

2. The magnetophoretic transdermal drug delivery hydrogel microneedle device according to claim 1, characterized in that: The ratio of the methyl vinyl ether-maleic acid copolymer to pectin is in the range of 10-15:

4.

3. The magnetophoretic transdermal drug delivery hydrogel microneedle device according to claim 1, characterized in that: The magnetic layer (4) comprises: PVP: 10-30wt%, NdFeB magnetic powder: 42-54wt%, ferrite magnetic powder: 28-36wt%, and lubricant: 0-3wt%.

4. The magnetophoretic transdermal drug delivery hydrogel microneedle device according to claim 1, characterized in that: Also includes: A backing layer (5), wherein the backing layer (5) is arranged on a side of the magnetic layer (4) away from the drug layer (3), and the area of ​​the backing layer (5) is larger than the areas of the drug layer (3) and the magnetic layer (4).

5. The magnetophoretic transdermal drug delivery hydrogel microneedle device according to claim 4, characterized in that: The backing layer (5) is made of any one of spunlace non-woven fabrics, polyurethane films, polyethylene films or other soft medical films that fit the skin.

6. The magnetophoretic transdermal drug delivery hydrogel microneedle device according to claim 1, characterized in that: Also includes: A sealing film (6), wherein the sealing film (6) is arranged on a side of the hydrogel microneedle (2) away from the base layer (1), and the sealing film (6) is detachably connected to the hydrogel microneedle (2).

7. The magnetophoretic transdermal drug delivery hydrogel microneedle device according to claim 6, characterized in that: The sealing film (6) is made of silicone oil paper.

8. The magnetophoretic transdermal drug delivery hydrogel microneedle device according to claim 1, characterized in that: The diameter of the hydrogel microneedle (2) is 50 to 200 μm, and the height of the hydrogel microneedle (2) is 200 to 800 μm.

9. The magnetophoretic transdermal drug delivery hydrogel microneedle device according to claim 1, characterized in that: The distance between adjacent hydrogel microneedles (2) is 500 to 800 μm.

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