Transdermal drug delivery system combining microneedle array and medicinal patch

Abstract

The utility model relates to the technical field of biomedicine and drug delivery, in particular to a transdermal drug delivery system combining a microneedle array and a medicinal patch, which comprises the microneedle array and the medicinal patch which are attached to each other, and the medicinal patch comprises a substrate layer, an anti-seepage film layer and a medicament layer which are sequentially arranged from bottom to top. The microneedle array is adhered to the upper surface of the medicament layer; the medicament layer comprises a limiting ring and ointment arranged in the limiting ring or a cotton core absorbing oily medicinal oil, and the limiting ring is adhered to the impermeable film layer. The microneedle array slightly penetrates through the surface layer of the skin, so that a channel for active ingredients in the medicinal patch to directly enter a human body is provided, and the absorption and treatment effects of medicines are enhanced; a new possibility is provided for treating chronic diseases, the medicine can be more accurately and rapidly permeated into the deep layer of the skin, rapid and accurate medicine administration is achieved, and therefore the living quality of a patient is improved.

Description

Technical Field

[0001] This invention relates to the fields of biomedicine and drug delivery technology, and in particular to a transdermal drug delivery system that combines a microneedle array with a pharmaceutical patch. Background Technology

[0002] With the fast pace of modern life, people face increasing life pressures, and irregular eating habits and insufficient physical exercise have become the norm. These factors combined have led to a significant increase in the incidence of chronic diseases, particularly metabolic diseases such as hyperlipidemia, hyperglycemia, and hypertension, as well as conditions like lumbar muscle strain and cervical spondylosis caused by long-term fatigue and unhealthy lifestyle habits. This trend not only reflects the widespread prevalence of sub-health but also highlights the limitations of existing treatments in meeting patients' needs. Among traditional treatments, physical therapies such as massage, acupuncture, and cupping, while effective in relieving pain, are inconvenient for patients due to their high cost and long treatment cycles. While Western medicine can quickly relieve certain symptoms, its potential side effects, especially for patients with chronic diseases requiring long-term medication, cannot be ignored. These issues have prompted the search for safer and more effective treatment options, and traditional Chinese medicine, with its unique therapeutic mechanisms and fewer side effects, has become particularly important in this context. The efficacy of traditional Chinese medicine (TCM) lies in its ability to comprehensively regulate multiple systems in the body. For chronic diseases such as hyperlipidemia, hyperglycemia, and hypertension, TCM can not only exert its effects through mechanisms such as adjusting lipid metabolism, improving pancreatic function, and lowering blood pressure, but also alleviate problems such as lumbar muscle strain and cervical spondylosis caused by long-term chronic diseases through effects such as relaxing muscles and promoting blood circulation, reducing inflammation, and relieving pain. However, traditional methods of administering TCM—such as direct oral administration or external application—have many limitations, making it difficult to ensure that the medicinal components can accurately and quickly reach the affected area or act deeply within the body.

[0003] When existing Chinese medicine patches are applied directly to the human body surface, the release rate of the drug is significantly affected because the skin barrier function hinders the penetration and diffusion of drug molecules, resulting in slow drug release.

[0004] Microneedle transdermal drug delivery technology can break through the skin barrier, enhancing drug absorption and therapeutic effects.

[0005] However, the existing microneedle transdermal drug delivery technologies are limited to the following:

[0006] ① The active pharmaceutical ingredient is mixed in a soluble or swellable microneedle material, and then the microneedle material mixed with the active pharmaceutical ingredient is used to prepare microneedles for transdermal drug delivery.

[0007] ② The active pharmaceutical ingredient is coated onto the surface of the microneedles for transdermal drug delivery;

[0008] ③ Encapsulate the active pharmaceutical ingredient in a soluble or swellable microneedle material for transdermal drug delivery;

[0009] The problems with transdermal drug delivery are: low drug content, and the inability to mix some drugs (such as large protein molecules and oily components) with microneedle materials due to their special physicochemical properties. Additionally, there is a tendency for drugs to be released rapidly in the initial stage (burst effect), making it difficult to achieve long-term sustained release and resulting in insufficient drug efficacy. Therefore, a transdermal drug delivery method is needed. Utility Model Content

[0010] The technical problem to be solved by this utility model is to overcome the shortcomings of the existing technology and provide a transdermal drug delivery system that combines a microneedle array and a pharmaceutical patch.

[0011] The technical solution adopted by this utility model to solve its technical problem is: a transdermal drug delivery system combining a microneedle array and a pharmaceutical patch, comprising a microneedle array and a pharmaceutical patch that are adhered to each other.

[0012] The aforementioned pharmaceutical patch comprises, from bottom to top, a base layer, an impermeable film layer, and a drug layer.

[0013] The microneedle array is adhered to the upper surface of the drug layer.

[0014] Furthermore, the microneedle array is a soluble bio-based microneedle array, or a swellable bio-based microneedle array with a specific porous structure, having an internal interconnected porosity ≥30% and a pore size of 10-100 μm. The porous structure of the microneedles in the microneedle array can enhance drug loading capacity and release controllability.

[0015] Furthermore, the agent layer includes a limiting ring and an ointment disposed within the limiting ring, the limiting ring being adhered to the impermeable membrane layer.

[0016] Furthermore, the agent layer includes a limiting ring and a cotton core containing oily medicine disposed within the limiting ring, the limiting ring being adhered to the impermeable film layer.

[0017] Furthermore, a sealing ring is provided between the microneedle array and the limiting ring. The upper surface of the sealing ring is bonded to the outer ring of the lower surface of the microneedle array, and the lower surface of the sealing ring is bonded to the inner ring of the upper surface of the limiting ring.

[0018] Furthermore, an adhesive is provided on the upper surface of the substrate layer.

[0019] Furthermore, the impermeable membrane layer is bonded to the center of the upper surface of the substrate layer.

[0020] The preparation of a transdermal drug delivery system includes the following steps:

[0021] 1. Preparation of soluble bio-based microneedle arrays or swellable bio-based microneedle arrays with porous structures:

[0022] When the microneedle array is a soluble bio-based microneedle array, the preparation process is as follows:

[0023] Dissolve hyaluronic acid or selected soluble or swellable bio-based materials in a suitable solvent;

[0024] Then, the above-mentioned bio-based material solution is poured into a microneedle mold, and a microneedle structure is formed through cooling or other solidification processes;

[0025] Next, the microneedle array is removed from the mold and subjected to necessary post-processing to enhance its physical stability. When the microneedle array is a swellable bio-based microneedle array with a porous structure, the fabrication process is as follows:

[0026] Dissolve hyaluronic acid or selected soluble or swellable bio-based materials in a suitable solvent;

[0027] Then, a pore-forming agent is added to the solution, or a gas foaming process (such as mechanical stirring and nitrogen injection) is introduced, or micron-sized biodegradable template particles (such as PLGA microspheres) are mixed in to form a porous structure of microneedles.

[0028] Then, the above-mentioned bio-based material solution is poured into a microneedle mold, and a microneedle structure is formed through cooling or other solidification processes;

[0029] Then, the microneedle array is removed from the mold, and a porous structure is formed by dissolving or degrading the porogen and template particles, and necessary post-processing is performed to enhance its physical stability.

[0030] In the above microneedle array preparation process, by controlling the molecular weight and cross-linking degree of hyaluronic acid, the dissolution or swelling rate of hyaluronic acid can be adjusted to obtain a soluble or swellable microneedle array.

[0031] 2. Preparation of pharmaceutical patches:

[0032] Prepare the medicinal ingredients according to the previously generated formula, based on specific treatment needs. Mix the medicinal ingredients with a suitable carrier material to form an application paste. Apply the paste evenly to a support material that matches the microneedle array.

[0033] 3. Combinations:

[0034] The prepared microneedle array is then attached to the surface of the pharmaceutical patch. Appropriate adhesive techniques are used to ensure a tight bond between the microneedle array and the patch, guaranteeing that the microneedles can effectively penetrate the skin during use, accelerating drug release and promoting drug absorption.

[0035] The beneficial effects of this invention are: it is compatible with different drug layers (ointments, oily cotton wicks), and the microneedle array slightly penetrates the skin surface, improving transdermal efficiency and enhancing drug absorption and therapeutic effects. The porous structure of the microneedle array can serve as a drug diffusion channel, further improving transdermal efficiency and accelerating drug release; it provides new possibilities for the treatment of chronic diseases, enabling more precise and rapid drug penetration into the deep layers of the skin, achieving rapid and accurate drug delivery, thereby improving patients' quality of life. Attached Figure Description

[0036] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0037] Figure 1 This is a schematic diagram of the structure of this utility model. Figure 1 ;

[0038] Figure 2 This is a utility model Figure 1 A cross-sectional schematic diagram;

[0039] Figure 3 This is a utility model Figure 1 Exploded view;

[0040] Figure 4 This is a schematic diagram of the structure of this utility model. Figure 2 ;

[0041] Figure 5 This is a utility model Figure 4 A cross-sectional schematic diagram;

[0042] Figure 6 This is a utility model Figure 4 Exploded view.

[0043] The numbers in the diagram are: 1-base layer, 2-impermeable membrane layer, 3-chemical layer, 31-limiting ring, 32-ointment, 33-cotton core, 4-sealing ring, 5-microneedle array. Detailed Implementation

[0044] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions of the embodiments of this utility model will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this utility model, not all embodiments. Based on the embodiments of this utility model, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of this utility model.

[0045] Example 1

[0046] Figures 1-3 The transdermal drug delivery system shown combines a microneedle array and a pharmaceutical patch, comprising a microneedle array 5 and a pharmaceutical patch that are adhered to each other. The microneedle array 5 includes a microneedle substrate and microneedles arranged in an array on the surface of the microneedle substrate. The microneedle substrate is circular.

[0047] The pharmaceutical patch comprises, from bottom to top, a base layer 1, an impermeable film layer 2, and a drug layer 3.

[0048] The microneedle array 5 is bonded to the upper surface of the drug layer 3;

[0049] The agent layer 3 includes a limiting ring 31 and an ointment 32 disposed within the limiting ring 31. The limiting ring 31 is adhered to the impermeable membrane layer 2.

[0050] When the transdermal drug delivery system is not in use, the ointment 32 is sealed by the cooperation of the impermeable film layer 2 and the microneedle array 5 with the limiting ring 31 to prevent leakage of the ointment 32.

[0051] An adhesive is applied to the upper surface of the base layer 1. The selected adhesive is harmless to the skin.

[0052] The impermeable membrane layer 2 is bonded to the center of the upper surface of the base layer 1, so that the base layer 1 can be bonded to the skin surface around its perimeter.

[0053] The microneedle array 5 is a soluble bio-based microneedle array, or the microneedle array 5 is a swellable bio-based microneedle array with a porous structure, the internal through-porosity is ≥30%, and the pore size is 10-100μm.

[0054] Because the microneedle array is a soluble or swellable microneedle array, it is essential to select a pharmaceutical patch that will not cause the microneedle array to dissolve or swell before use. Accordingly, this transdermal drug delivery system can be stored in sealed packaging.

[0055] In use, this transdermal drug delivery system, which combines a microneedle array and a medicated patch, is attached to the skin surface through the adhesive side of the base layer 1 to fix the transdermal drug delivery system to the affected area. The microneedles of the microneedle array 5 will slightly penetrate the skin surface, providing a channel for the active ingredients in the medicated patch to directly enter the body, and promoting the active ingredients in the medicated patch to bypass the skin stratum corneum barrier of the affected area and penetrate into the human body.

[0056] Then, under the action of sweat and body fluids at the affected area, the microneedle array 5 dissolves or swells, allowing the active ingredients in the medicated patch to enter the human body through the dissolved or swollen microneedle array 5 and the channels opened by the microneedles.

[0057] Once the active ingredients in the medicated patch are fully absorbed by the body, peel off the base layer 1, and the transdermal drug delivery system can be completely removed.

[0058] The preparation of a transdermal drug delivery system includes the following steps:

[0059] 1. When the microneedle array 5 is a swellable bio-based microneedle array with a porous structure, the preparation of the microneedle array includes the following steps:

[0060] Solution preparation: Dissolve hyaluronic acid or a selected swellable bio-based material (such as gelatin or polyvinyl alcohol) in deionized water or a buffer solution to prepare a homogeneous solution with a concentration of 10%-30% (w / v). Sodium hyaluronate is preferred as it has high solubility (especially at low temperatures), a pH closer to neutral (6.5-7.5), and less skin irritation.

[0061] Then, 0.5%-5% (w / w) of pore-forming agent (such as sodium bicarbonate or mannitol) is added to the solution, or a gas foaming process (such as mechanical stirring and nitrogen injection) is introduced, or micron-sized biodegradable template particles (such as PLGA microspheres) are mixed in to form a porous structure of microneedles.

[0062] Microneedle mold preparation: Select a suitable microneedle mold with a microneedle length of 0.5-1.5mm.

[0063] Casting and solidification: Pour the above solution into a microneedle mold and place it at 4°C for 24 hours to solidify and form.

[0064] Demolding and cleaning: Remove the solidified microneedle array from the mold, clean it with deionized water or ethanol to remove pore-forming agents or template particles, and perform necessary post-treatment to enhance its physical stability.

[0065] In the above microneedle array preparation process, the molecular cross-linking network of the material is controlled by adjusting the concentration of cross-linking agent or the reaction time, thereby adjusting the dissolution / swelling rate (low cross-linking degree accelerates dissolution, high cross-linking degree promotes swelling);

[0066] Porosity verification: Scanning electron microscopy (SEM) was used to observe the pore distribution on the surface and inside of the microneedles to ensure that the pore size range was 10-100 μm and the porosity was ≥30%.

[0067] When the microneedle array 5 is a soluble bio-based microneedle array, the preparation of the microneedle array includes the following steps:

[0068] Solution preparation: Dissolve hyaluronic acid or a selected swellable bio-based material (such as gelatin or polyvinyl alcohol) in deionized water or a buffer solution to prepare a homogeneous solution with a concentration of 10%-30% (w / v). Sodium hyaluronate is preferred as it has high solubility (especially at low temperatures), a pH closer to neutral (6.5-7.5), and less skin irritation.

[0069] Microneedle mold preparation: Select a suitable microneedle mold with a microneedle length of 0.5-1.5mm.

[0070] Casting and solidification: Pour the above solution into a microneedle mold and place it at 4°C for 24 hours to solidify and form.

[0071] Demolding: The solidified microneedle array is removed from the mold and subjected to necessary post-processing to enhance its physical stability.

[0072] 2. Preparation of medicinal patches

[0073] 2.1 Preparation of drug gel

[0074] 2.1.1 Preparation method A

[0075] 2.1.1.1 Material Preparation:

[0076] Active ingredients 1g: Extracts of hangover relieving herbs (such as kudzu root extract, atractylodes macrocephala, licorice), extracts of blood sugar lowering herbs (such as bitter melon extract, coptis chinensis, salvia miltiorrhiza, etc.), extracts of weight loss herbs (such as purified water, peony root extract, grape seed extract, angelica root extract, plum extract, white extract: oxyethyl alcohol, olive fruit extract, broom leaf Australian tea buds / leaf oil, non-extract, mountain extract, medicinal rhubarb extract, cyperus rotundus root extract, costus root extract, eugenol extract, nutmeg extract, artemisia argyi extract, glycerin, clear, sodium lactone, carnitine, glycerol, butylene glycol, xanthan gum, capsaicin, transfructose HCA, glycine aluminum, tartaric acid, EDTA dimethyl ether, oligopeptide-1, 1,2-hexanediol, hesperidin, ethylhexylglycerin, p-hydroxyacetophenone, butylbenzene, etc.);

[0077] 5g of gel matrix: such as sodium carboxymethyl cellulose, gelatin, etc.;

[0078] 100mL of distilled water.

[0079] 2.1.1.2 Preparation process:

[0080] Slowly add the gel matrix to distilled water while stirring to prevent lumps from forming. Heat to 60°C and continue stirring until completely dissolved, approximately 20 minutes. Add the active ingredient to the gel matrix solution and continue stirring for 30 minutes to ensure uniform mixing.

[0081] 2.1.2 Preparation Method B

[0082] Melt beeswax in a hot water bath, add olive oil and glycerin to adjust to the desired viscosity, and then slowly add the active ingredients from preparation method A to the beeswax mixture while stirring to ensure uniform mixing.

[0083] 2.2 Coating and Drying:

[0084] The mixed drug gel is evenly coated onto the impermeable membrane layer 2 and filled into the limiting ring 31 with a thickness of about 0.5-1 mm. It is then placed at room temperature to dry naturally, or dried in a drying oven at 45°C for 2-4 hours to obtain the ointment 32.

[0085] 3. Combination

[0086] The prepared microneedle array is then attached to the designated area of ​​the medicinal patch. Finally, the combined microneedle array and medicinal patch are sterilized and packaged, and stored in a cool, dry place, away from direct sunlight and high temperatures.

[0087] Taking into account both absorption time and human skin healing time, the microneedle array is selected to be either a soluble microneedle array or a swellable microneedle array.

[0088] If the absorption time of the active ingredient is long, such as more than 6 hours, a swellable microneedle array can be selected to avoid the healing of the channels opened by the microneedles. After the microneedles of the microneedle array 5 slightly penetrate the skin surface, the swellable microneedle array swells, and the active ingredient can diffuse into the human body through the channels opened by the microneedles penetrating the skin surface. The porous structure of the swellable microneedle array can serve as a drug diffusion channel, further improving transdermal efficiency and accelerating drug release. The time for the active ingredient to diffuse into the human body through the swellable microneedles is shorter than the time for the active ingredient to enter the human body through the skin barrier.

[0089] If the absorption time of the active ingredient is short, within 6 hours, a soluble microneedle array can be selected. After the microneedles of the microneedle array 5 slightly penetrate the skin surface, the soluble microneedle array dissolves, and the active ingredient in the medicated patch can diffuse into the human body through the dissolved microneedle array 5 and the channels opened by the microneedles penetrating the skin surface.

[0090] When medicated patches are applied directly to the human body, it takes approximately 12-72 hours for the active ingredients in the patches to be fully absorbed. Due to various lifestyle factors, medicated patches are usually removed or replaced within 24 hours, resulting in the patches being discarded before the active ingredients are fully absorbed, thus causing waste.

[0091] Example 2

[0092] like Figures 4-6 As shown, the difference from Example 1 is that:

[0093] The agent layer 3 includes a limiting ring 31 and a cotton core 33 containing oily medicine disposed within the limiting ring 31. The limiting ring 31 is adhered to the impermeable membrane layer 2.

[0094] A sealing ring 4 is provided between the microneedle array 5 and the limiting ring 31. The upper surface of the sealing ring 4 is bonded to the outer ring of the lower surface of the microneedle array 5, and the lower surface of the sealing ring 4 is bonded to the inner ring of the upper surface of the limiting ring 31.

[0095] When the transdermal drug delivery system is not in use, the oily drug solution is sealed by the cooperation of the impermeable film layer 2, the microneedle array 5, the sealing ring 4, and the limiting ring 31 to prevent leakage of the oily drug solution.

[0096] Preparation of oily medicinal solutions

[0097] 1. Preparation method

[0098] 1.1 Material Preparation:

[0099] Active ingredients: 1ml of essential oil (such as peppermint essential oil, lavender essential oil, tea tree essential oil, etc.), 1g of medicinal powder (such as turmeric powder, Ganoderma lucidum powder, etc.);

[0100] Carrier substrate: cotton core;

[0101] Stabilizer: Vitamin E 0.5g;

[0102] Conditioner: 5ml vegetable oil (such as sweet almond oil), 5ml glycerin.

[0103] 1.2 Preparation process:

[0104] The essential oil and medicinal powder are mixed evenly in a certain proportion to form an oily substance. Stabilizers and conditioners are added at the same time, and then dripped into the carrier matrix.

[0105] The pharmaceutical patch in Example 2 contains oily components. In addition to using hyaluronic acid from Example 1 for preparation, the microneedle array 5 can also be prepared using other non-oil-soluble bio-based materials.

[0106] The above description is only a preferred embodiment of the present utility model, but the protection scope of the present utility model is not limited thereto. Any equivalent substitutions or changes made by those skilled in the art within the technical scope disclosed in the present utility model, based on the technical solution and the inventive concept of the present utility model, should be included within the protection scope of the present utility model.

Claims

1. A transdermal drug delivery system combining a microneedle array and a pharmaceutical patch, characterized in that: This includes interlocking microneedle arrays (5) and pharmaceutical patches. The aforementioned pharmaceutical patch comprises, from bottom to top, a base layer (1), an impermeable film layer (2), and a drug layer (3). The microneedle array (5) is bonded to the upper surface of the drug layer (3).

2. The transdermal delivery system of claim 1, wherein the microneedle array is combined with a patch for pharmaceutical use. The microneedle array (5) is a soluble bio-based microneedle array, or the microneedle array (5) is a swellable bio-based microneedle array with a porous structure, the internal through-porosity is ≥30%, and the pore size is 10-100μm.

3. The transdermal delivery system of claim 1, wherein the microneedle array is combined with a patch for pharmaceutical use. The agent layer (3) includes a limiting ring (31) and an ointment (32) disposed within the limiting ring (31), and the limiting ring (31) is adhered to the impermeable membrane layer (2).

4. The transdermal delivery system of claim 1, wherein the microneedle array is combined with a patch for pharmaceutical use. The agent layer (3) includes a limiting ring (31) and a cotton core (33) containing oily medicine solution disposed in the limiting ring (31). The limiting ring (31) is bonded to the impermeable film layer (2).

5. The transdermal delivery system of claim 4, wherein the microneedle array is combined with a patch. A sealing ring (4) is provided between the microneedle array (5) and the limiting ring (31). The upper surface of the sealing ring (4) is bonded to the outer ring of the lower surface of the microneedle array (5), and the lower surface of the sealing ring is bonded to the inner ring of the upper surface of the limiting ring (31).

6. The transdermal delivery system of claim 1, wherein the microneedle array is combined with a patch. An adhesive is provided on the upper surface of the base layer (1).

7. The transdermal delivery system of claim 1, wherein the microneedle array is combined with a patch. The impermeable membrane layer (2) is bonded to the center of the upper surface of the base layer (1).

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