CN109481422B - Graphene oxide electrothermal film transdermal patch - Google Patents

Abstract

The invention discloses a graphene oxide electrothermal film transdermal patch, which sequentially comprises the following components from top to bottom: the graphene oxide electrothermal film comprises a graphene oxide electrothermal film, a backing film, a drug storage and a protective film. Compared with the traditional patch, the graphene oxide electrothermal film transdermal patch can maintain the patch at a certain temperature higher than the body temperature, so that the lipid structure of the skin is changed, the medicine is promoted to permeate the skin, and the treatment effect is improved; the skin surface maintains the set temperature for a long time, the muscles and the tendons are relaxed, the blood circulation is promoted, the pain is favorably relieved, the treatment effect is obvious, the warm and comfortable feeling is realized, and the medicine compliance of patients is improved. In addition, the graphene oxide electrothermal film transdermal patch can controllably output heat and accurately regulate temperature, so that long-time continuous and stable heating is realized, and the administration dosage is more accurate; adopt detachable mode bonding, can realize in time interrupting heat supply and electric heat membrane reuse.

Description

A kind of graphene oxide electrothermal film transdermal patch

technical field

The invention relates to the technical field of medicine. More specifically, it relates to a graphene oxide electrothermal film transdermal patch.

Background technique

Compared with traditional drug delivery methods, the transdermal drug delivery technology has many advantages, avoiding the "first-pass effect" of the drug on the liver and the decomposition of the gastrointestinal tract, and improving the therapeutic effect; maintaining a relatively stable blood drug concentration and avoiding peaks and valleys Phenomena, reduce side effects; prolong administration time, reduce administration frequency, improve patient compliance. These unique advantages have attracted many pharmaceutical industry sectors to develop new transdermal formulations.

Because the skin acts as a barrier to the transdermal absorption of drugs, especially the stratum corneum, the outermost "brick wall structure" of the skin. While protecting the body from foreign substances, it acts as a rate-limiting barrier for any drug molecule. In order to increase the transdermal penetration of drugs, various new methods to enhance transdermal delivery are emerging. The use of chemical skin enhancers can increase the passive transdermal penetration of small molecule drugs and cannot overcome the size limiting factor of macromolecular drugs. Another common disadvantage of penetration enhancers is their tendency to cause skin sensitization due to their increased transdermal permeability of drugs by disturbing the ordered stratum corneum lipid bilayer or corneocyte structure.

Physical permeation enhancement technology uses a combination of devices to improve drug permeation. For example, active drug delivery technologies that use external energy to promote drug penetration include pressure-driven jets, iontophoresis skin patches, microneedles, lasers, and heating. Way. It has played a great role in expanding the types of drugs applicable to the field of transdermal drug delivery.

Achievements in materials science and nanotechnology have facilitated the development of various materials as drug carriers. Especially graphene-based materials, due to their high loading capacity, the use of external stimuli such as pH, electricity, electrochemical, light, etc. to initiate drug release in graphene matrices has attracted great attention in this field. For drugs that need to be released for a long time, heating to enhance penetration is an effective method. Due to its excellent performance, graphene oxide has good application prospects in the fields of heat-conducting and heat-dissipating materials, electric heating films, catalyst supports, etc., and its attention in the field of drug release is also getting higher and higher. In the research of graphene oxide as a drug carrier, it is found that the release of drugs driven by the electrothermal effect generated by electrical excitation is one of the most effective ways. Thermally controlled drug delivery systems typically trigger drug release from the carrier by heat. The transdermal penetration rate of drugs can be controlled by heat-activated patches, which provides a solution for long-term controlled release of active ingredients.

Traditional hyperthermia methods usually preheat carriers such as volcanic mud packs and thermal storage gels as latent heat storage, or release heat through the oxidation process of iron powder. In addition, substances such as capsaicin can be added to the patch to stimulate the skin to produce a subjective sense of heat.

However, the common disadvantages of the above-mentioned methods are that they cannot provide heat in a controllable manner, cannot precisely adjust the temperature of action, and cannot achieve long-term continuous and stable heating. And since the exothermic substance is incorporated into the patch, the heat supply cannot be interrupted without removing the patch from the patient's skin.

Contents of the invention

The object of the present invention is to provide a graphene oxide electrothermal film transdermal patch, which can output heat controllably through the electrothermal effect generated by electrically exciting the graphene oxide film, promotes the release of the drug, and improves the transdermal penetration of the drug. Has a good therapeutic effect.

To achieve the above object, the present invention adopts the following technical solutions:

The invention provides a graphene oxide electric heating film transdermal patch, which comprises: a graphene oxide electric heating film, a backing film, a drug storage and a protective film from top to bottom.

Further, the graphene oxide electrothermal film is heated by connecting a power source, and the action temperature is 35-50°C, preferably 40-45°C.

Further, the graphene oxide electrothermal film is detachably bonded to the backing film, preferably by heat-resistant glue.

Further, the graphene oxide electrothermal film includes a graphene oxide conductive layer and an insulating protective layer.

Further, the material of the insulating protection layer is polyimide, polyethylene terephthalate or a mixture of two, and its resistance is 2-20Ω.

Further, the drug reservoir is a hydrogel or a pressure-sensitive adhesive patch.

Further, the raw materials of the hydrogel include raw materials, polymer skeleton materials, moisturizing agents, viscous agents, and fillers. When the drug reservoir is a hydrogel, the preparation method of the graphene oxide electrothermal film transdermal patch is generally as follows: after mixing the raw materials, add them to water to stir, mix and disperse, leave to stand to remove air bubbles to obtain ointment, and apply the ointment with a certain thickness. Spread on the protective layer with a coating thickness of 0.1-2mm, preferably 0.3-1mm to cover the backing film, press it tightly, cut into patches with an area of ^5-100cm2 , and stick graphite oxide on the backing film ene electric heating film, that is.

Preferably, the polymer skeleton material includes but is not limited to one or more of acrylate, polyvinyl alcohol, gelatin, sodium polyacrylate, cellulose derivatives, chitosan derivatives, polyvinylpyrrolidone, and wormwood The mixture of species; the viscous agent includes but not limited to polyacrylic acid and its sodium salt. Moisturizing agent includes: glycerin, propylene glycol, the mixture of one or more in sorbitol; Said filler includes but not limited to micropowder silica gel, calcium carbonate, kaolin, bentonite, titanium dioxide, zinc oxide, talc in one or more mixture of species.

Further, the raw materials of the pressure-sensitive adhesive patch include bulk drug, pressure-sensitive adhesive and solubilizer. When the drug reservoir is a pressure-sensitive adhesive patch, the preparation method of the graphene oxide electrothermal film transdermal patch is generally as follows: after mixing each raw material, add it to the pressure-sensitive adhesive and stir and mix evenly, leave it to stand for 1 hour to remove air bubbles, and obtain Drug glue: apply the drug-containing glue on the protective layer with a thickness of 300-600 μm, dry at 70-90°C for 10-20 minutes, take out the covering film after drying, press it tightly, and cut into The patch with an area range of 5-100cm ² is obtained by bonding a graphene oxide electrothermal film on the backing film.

Preferably, the pressure-sensitive adhesive is selected from acrylate pressure-sensitive adhesive or polyisobutylene pressure-sensitive adhesive according to the properties of the bulk drug; the solubilizer includes but is not limited to one of lactic acid, sodium lactate, boric acid, citric acid, tartaric acid A mixture of several.

Further, the raw materials can be active ingredients of cosmetics and pharmaceuticals, and the raw materials in pressure-sensitive adhesive patches and hydrogels are selected according to the properties of the raw materials, including but not limited to active ingredients for pain relief, fat-reducing Active ingredients, effective ingredients for removing scars, active ingredients for whitening, rheumatism and rheumatoid drugs or a mixture of several. Preferably, the active ingredients for pain relief include but are not limited to acetaminophen, non-steroidal anti-inflammatory drugs (such as: ibuprofen, naproxen, aspirin, fenoprofen, flurbiprofen, ketoprofen, Oxaprozin, diclofenac sodium, etodolac, indomethacin ketorolac, sulindac tolmetin meclofenamate/ester, mefenamic acid, nabumetone piroxicam and COX- 2 inhibitors, etc.), corticosteroids (such as cortisone), anesthetics, anticonvulsants (such as gabapentin, pregabalin), local anesthetics (such as diphenhydramine hydrochloride, chlorpheniramine maleate, etc.) histamine; anesthetics such as pentobarbital sodium), etc.; the active ingredients for reducing fat include but are not limited to L-carnitine, orlistat, dimethyl biguanide; the active ingredients for removing scars include but are not limited to triamcinolone acetonide , earthworm polypeptide, carnosine, asiaticoside, hirudin, ginsenoside; the whitening active ingredients include but not limited to ascorbic acid, magnesium ascorbyl phosphate, tranexamic acid, ascorbylglucoside, ascorbyl palmitate, licorice extract extract, yeast extract, trametes, aspergillus, exophilia, resveratrol and derivatives resveratrol phosphate, resveratrol ferulate, oxidation Resveratrol, Ferulic Acid and Its Derivatives, Azelaic Acid, Azelaic Acid Derivatives, Kojic Acid, Ellagic Acid, Hinokitiol, Soybean Extract, Scutellaria Scutellariae Extract, Mulberry Extract, Molasses, Tetrahydro Curcumin, Glycyrrhetinic Acid, Refined Niacinamide, Pomegranate, Grape Seed Extract, Weipu Hops, BV-OSC-Tetrahexyldecyl Ascorbate, Ascorbyl Disodium Hydrogen Phosphate, Ascorbyl Glucoside, α(β)-Uva Uva Glycosides, ascorbyl palmitate, resorcinol and tranexamic acid; the rheumatism and rheumatoid drugs include but not limited to diclofenac sodium, diclofenac diethylamine, Anluotong, Qianjinsong, safflower extract, blood jellyfish extract, Clematis clematis extract, cloverleaf extract, etc.; the anti-wrinkle active ingredients include but not limited to sheep placenta, retinol, retinyl acetate, vitamin A palmitate, retinoic acid, vitamin A acetate vitamin C and its derivatives.

Preferably, the content range of the raw material drug in the graphene oxide electrothermal film transdermal patch per square centimeter is 0.2-2 mg.

Further, the backing film is one or more layers of composite films, and its material includes one or more of polyethylene terephthalate, polypropylene, polyethylene, ethylene-vinyl acetate copolymer, and polyurethane mixture.

Further, the thickness of the backing film is 30-300 μm.

Further, the material of the protective film is a mixture of one or more of polyethylene terephthalate, polyethylene, and polypropylene films whose surface has been treated with plasma, fluorine-coated or silicon-coated, preferably fluorine-coated Processed polyethylene terephthalate.

Further, the thickness of the protective film is 20-300 μm.

The beneficial effects of the present invention are as follows:

1. Compared with the traditional patch, the graphene oxide electrothermal film transdermal patch of the present invention can maintain the patch at a certain temperature higher than body temperature, change the lipid structure of the skin, promote the penetration of drugs through the skin, and improve the therapeutic effect; The skin surface maintains the set temperature for a long time, relaxes tendons and activates blood circulation, promotes blood circulation, is beneficial to relieve pain, has remarkable therapeutic effect, is warm and comfortable, and improves patients' drug compliance.

2. The graphene oxide electrothermal film transdermal patch of the present invention can controllably output heat and precisely adjust temperature, and realize long-term continuous and stable heating, so that the dosage is more accurate.

3. The graphene oxide electrothermal membrane transdermal patch of the present invention is bonded in a detachable manner, which can realize timely interruption of heating and reuse of the electrothermal membrane.

Description of drawings

The specific implementation manners of the present invention will be further described in detail below in conjunction with the accompanying drawings.

Figure 1 shows a schematic side view of the graphene oxide electrothermal film transdermal patch of the present invention; wherein 1-graphene oxide electrothermal film, 2-backing film, 3-drug storage, 4-protective film.

Figure 2 shows a 3.5mm circular graphene oxide electrothermal film: A, a physical map of the graphene oxide electrothermal film; B, a thermal imager diagram of the graphene oxide electrothermal film.

Figure 3 shows the cumulative release amount (absolute value) in 24 hours of the formula patch of Example 1: a, attaching the electric heating film at 45°C; b, attaching the electric heating film at 40°C; c, attaching the electric heating film and heating at 50°C; d, No heating film attached.

Figure 4 shows the graphene oxide electrothermal film attached to the surface of the skin to measure the relationship between temperature and voltage, resistance.

Figure 5 shows the histopathological section observation after the graphene oxide electric heating film is attached to the surface of human skin and heated: A, normal skin; B, graphene oxide electric heating film at 40°C for 24 hours; C, graphene oxide electric heating film at 45°C 24h; D. Graphene oxide electric heating film at 50°C for 24h.

Detailed ways

In order to illustrate the present invention more clearly, the present invention will be further described below in conjunction with preferred embodiments and accompanying drawings. Similar parts in the figures are denoted by the same reference numerals. Those skilled in the art should understand that the content specifically described below is illustrative rather than restrictive, and should not limit the protection scope of the present invention.

The invention provides a graphene oxide electric heating film transdermal patch, which comprises: a graphene oxide electric heating film, a backing film, a drug storage and a protective film from top to bottom.

Further, the graphene oxide electrothermal film is heated by connecting the power supply, and the action temperature is 35-50°C, preferably 40-45°C, for example, it can be 35°C, 40°C, 45°C, 50°C and so on. The present invention realizes long-term continuous and stable heating through controllable heat output and precise temperature adjustment, thereby making the dosage more accurate.

Further, the graphene oxide electrothermal film is detachably bonded to the backing film, preferably by heat-resistant glue. When in use, the protective layer is torn off, the drug reservoir is pasted on the skin, and the graphene oxide electric heating film is connected to the power supply to maintain a suitable temperature, which promotes the penetration of the drug through the skin and enhances the therapeutic effect. It can realize timely interruption of heating and reuse of the electric heating film.

Further, the graphene oxide electrothermal film includes a graphene oxide conductive layer and an insulating protective layer.

Further, the material of the insulating protection layer is polyimide, polyethylene terephthalate or a mixture of two, and its resistance is 2-20Ω.

Further, the drug reservoir is a hydrogel or a pressure-sensitive adhesive patch.

Further, the raw materials of the hydrogel include raw materials, polymer skeleton materials, moisturizing agents, viscous agents, and fillers. When the drug reservoir is a hydrogel, the preparation method of the graphene oxide electrothermal film transdermal patch is generally as follows: after mixing the raw materials, add them to water to stir, mix and disperse, leave to stand to remove air bubbles to obtain ointment, and apply the ointment with a certain thickness. Spread on the protective layer with a coating thickness of 0.1-2mm, preferably 0.3-1mm to cover the backing film, press it tightly, cut into patches with an area of ^5-100cm2 , and stick graphite oxide on the backing film ene electric heating film, that is.

Preferably, the polymer skeleton material includes but is not limited to one or more of acrylate, polyvinyl alcohol, gelatin, sodium polyacrylate, cellulose derivatives, chitosan derivatives, polyvinylpyrrolidone, and wormwood The mixture of species; the viscous agent includes but not limited to polyacrylic acid and its sodium salt. Moisturizing agent includes: glycerin, propylene glycol, the mixture of one or more in sorbitol; Said filler includes but not limited to micropowder silica gel, calcium carbonate, kaolin, bentonite, titanium dioxide, zinc oxide, talc in one or more mixture of species.

Further, the raw materials of the pressure-sensitive adhesive patch include bulk drug, pressure-sensitive adhesive and solubilizer. When the drug reservoir is a pressure-sensitive adhesive patch, the preparation method of the graphene oxide electrothermal film transdermal patch is generally as follows: after mixing each raw material, add it to the pressure-sensitive adhesive, stir and mix evenly, leave it to stand for 1 hour to remove air bubbles, and obtain Drug glue: apply the drug-containing glue on the protective layer with a thickness of 300-600 μm, dry at 70-90°C for 10-20 minutes, take out the covering film after drying, press it tightly, and cut into The patch with an area range of 5-100cm ² is obtained by bonding a graphene oxide electrothermal film on the backing film.

Preferably, the pressure-sensitive adhesive is selected from acrylate pressure-sensitive adhesive or polyisobutylene pressure-sensitive adhesive according to the properties of the bulk drug; the solubilizer includes but is not limited to one of lactic acid, sodium lactate, boric acid, citric acid, tartaric acid A mixture of several. The solubilizing agent of the present invention can effectively increase the solubility of the bulk drug in the pressure-sensitive adhesive.

Further, the raw materials can be active ingredients of cosmetics and pharmaceuticals, and the raw materials in pressure-sensitive adhesive patches and hydrogels are selected according to the properties of the raw materials, including but not limited to active ingredients for pain relief, fat-reducing Active ingredients, effective ingredients for removing scars, active ingredients for whitening, rheumatism and rheumatoid drugs or a mixture of several. Preferably, the active ingredients for pain relief include but are not limited to acetaminophen, non-steroidal anti-inflammatory drugs (such as: ibuprofen, naproxen, aspirin, fenoprofen, flurbiprofen, ketoprofen, Oxaprozin, diclofenac sodium, etodolac, indomethacin ketorolac, sulindac tolmetin meclofenamate/ester, mefenamic acid, nabumetone piroxicam and COX- 2 inhibitors, etc.), corticosteroids (such as cortisone), anesthetics, anticonvulsants (such as gabapentin, pregabalin), local anesthetics (such as diphenhydramine hydrochloride, chlorpheniramine maleate, etc.) histamine; anesthetics such as pentobarbital sodium), etc.; the active ingredients for reducing fat include but are not limited to L-carnitine, orlistat, dimethyl biguanide; the active ingredients for removing scars include but are not limited to triamcinolone acetonide , earthworm polypeptide, carnosine, asiaticoside, hirudin, ginsenoside; the whitening active ingredients include but not limited to ascorbic acid, magnesium ascorbyl phosphate, tranexamic acid, ascorbylglucoside, ascorbyl palmitate, licorice extract extract, yeast extract, trametes, aspergillus, exophilia, resveratrol and derivatives resveratrol phosphate, resveratrol ferulate, oxidation Resveratrol, Ferulic Acid and Its Derivatives, Azelaic Acid, Azelaic Acid Derivatives, Kojic Acid, Ellagic Acid, Hinokitiol, Soybean Extract, Scutellaria Scutellariae Extract, Mulberry Extract, Molasses, Tetrahydro Curcumin, Glycyrrhetinic Acid, Refined Niacinamide, Pomegranate, Grape Seed Extract, Weipu Hops, BV-OSC-Tetrahexyldecyl Ascorbate, Ascorbyl Disodium Hydrogen Phosphate, Ascorbyl Glucoside, α(β)-Uva Uva Glycosides, ascorbyl palmitate, resorcinol and tranexamic acid; the rheumatism and rheumatoid drugs include but not limited to diclofenac sodium, diclofenac diethylamine, Anluotong, Qianjinsong, safflower extract, blood jellyfish extract, Clematis clematis extract, cloverleaf extract, etc.; the anti-wrinkle active ingredients include but not limited to sheep placenta, retinol, retinyl acetate, vitamin A palmitate, retinoic acid, vitamin A acetate vitamin C and its derivatives.

Preferably, the content range of the raw material drug in the graphene oxide electrothermal film transdermal patch per square centimeter is 0.2-2 mg. For example, it can be 0.2 mg, 0.5 mg, 1 mg, 1.5 mg, 2 mg and so on.

Further, the backing film is one or more layers of composite films, and its material includes one or more of polyethylene terephthalate, polypropylene, polyethylene, ethylene-vinyl acetate copolymer, and polyurethane mixture.

Further, the thickness of the backing film is 30-300 μm. For example, it may be 30 μm, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm and so on.

Further, the material of the protective film is a mixture of one or more of polyethylene terephthalate, polyethylene, and polypropylene films whose surface has been treated with plasma, fluorine-coated or silicon-coated, preferably fluorine-coated Processed polyethylene terephthalate.

Further, the thickness of the protective film is 20-300 μm. For example, it can be 20 μm, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm and so on.

The present invention will be further described by specific examples below.

In the present invention, unless otherwise specified, the raw materials and equipment used can be purchased from the market or commonly used in this field. The methods in the following examples, unless otherwise specified, are conventional methods in the art.

Example 1 Diclofenac Sodium Analgesic Transdermal Patch

1. Drug storage formula:

2. Patch preparation

Add diclofenac sodium to ethanol, add lactic acid after mixing to dissolve diclofenac sodium, add DURO-TAK87-2677 medical pressure-sensitive adhesive (containing acrylate and vinyl acetate copolymer 39.5%, ethyl acetate 22.4%, isopropyl Alcohol 22.4%, heptane 12.7%, toluene 3%), 60 ° C constant temperature magnetic stirring for 1 hour, stand still for 1 hour to remove air bubbles, coat on the protective film with a coating thickness of 300 μm, dry at 70 ° C for 20 minutes, cover the back Lining film, pressing, cutting, bonding graphene oxide electric heating film on the backing film, sealed and stored in aluminum-plastic bag.

When in use, the protective film is torn off, the drug storage layer is pasted on the skin, and the graphene oxide electric heating film is connected to the power supply for heating. After completion, the graphene oxide electric heating film can be reused.

The in vitro transdermal test of the graphene oxide electrothermal film transdermal patch obtained in this example through the pig ear skin: using the improved Franz diffusion cell, the pig ear skin was fixed on the diffusion cell, the dermis faced the receiving chamber, and the horny layer faced the supply chamber . The patch is applied on the stratum corneum, and an appropriate amount of pH=7.4 phosphate buffer is added to the receiving room, and the 37°C constant temperature water bath is circulated and magnetically stirred for 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours for sampling. The concentration of the sample was measured by high performance liquid chromatography, and the results are shown in Figure 3. It can be seen from the figure that heating with graphene oxide electrothermal film has obvious effect of promoting penetration. The graphene oxide electric heating film was attached to the skin surface, and the two poles were connected to the output terminal of the DC regulated power supply. The relationship between the measured temperature, voltage and resistance was shown in Figure 4. In the voltage range of 0-2.5V, the electric heating film can maintain the skin surface at a maximum temperature of 48°C. Observation by HE staining of tissue paraffin sections, the results are shown in Figure 5, it can be seen that the stratum corneum and epidermis of normal skin are intact, without damage, and rich in muscle fibers. Heating at 40°C and 45°C can loosen the stratum corneum of the skin, It is helpful for the drug to penetrate through the skin. The transdermal penetration is the highest at 45°C, which can increase the transdermal permeability of the patch by 4.2 times. Heating at 50°C will have a certain destructive effect on the stratum corneum.

Example 2 L-carnitine fat-reducing transdermal patch

1. Drug storage formula:

2. Patch preparation:

Add sodium carboxymethyl cellulose, artemisia gum, glycerin, micronized silica gel and kaolin into water, stir and mix evenly. Add L-carnitine and mechanically stir to make it evenly mixed. Coat 500 μm on the protective film. Cover the backing film, press it tightly, cut it, bond the graphene oxide electric heating film on the backing film, and store it in an aluminum-plastic bag. Using method is the same as embodiment 1.

The results of in vitro transdermal test showed that the cumulative release amount of the patch could reach 39.71 μg/cm ² in 24 hours.

Example 3 triamcinolone acetonide acetate transdermal patch for removing scars

1. Drug storage formula:

Triamcinolone Acetate 3g

DURO-TAK 387-2510 Medical Pressure Sensitive Adhesive 77g

Glycerin 20g

2. Patch preparation:

Add glycerin and triamcinolone acetonide acetate to DURO-TAK 387-2510 medical pressure-sensitive adhesive (containing 40.5% acrylate polymer, 54.1% ethyl acetate, 5.4% hexane), and mix evenly with constant temperature magnetic stirring at 60°C to make it completely dissolved. Let stand for 1 hour to remove air bubbles. Coat 600 μm on the protective film, dry at 90°C for 10 minutes, cover the backing film, press it, cut it, stick the graphene oxide electric heating film on the backing film, and store it in an aluminum-plastic bag. Using method is the same as embodiment 1.

The results of in vitro transdermal test showed that the cumulative release amount of the patch could reach 23.83 μg/cm ² in 24 hours.

Embodiment 4 ascorbic acid whitening transdermal patch

1. Drug storage formula:

2. Patch preparation:

Add polyvinylpyrrolidone, polyethylene glycol, propylene glycol and calcium carbonate into water, stir and mix evenly. Add ascorbic acid and stir mechanically to make it evenly mixed. Coat 1mm on the protective film. Cover the backing film, press it tightly, cut it, bond the graphene oxide electric heating film on the backing film, and store it in an aluminum-plastic bag. Using method is the same as embodiment 1.

The results of in vitro transdermal test showed that the cumulative release amount of the patch could reach 28.59 μg/cm ² in 24 hours.

Embodiment 5 diclofenac diethylamine rheumatism transdermal patch

1. Drug storage formula:

2. Patch preparation

Add diclofenac diethylamine to ethanol, mix well and add sodium lactate to promote the dissolution of diclofenac diethylamine, add DURO-TAK 87-2677 medical pressure-sensitive adhesive, stir for 1 hour at constant temperature at 60°C, and let it stand for 1 hour to remove air bubbles. Coating on the protective film with a coating thickness of 200 μm, drying at 80°C for 15 minutes, covering the backing film, pressing, cutting, bonding the graphene oxide electric heating film on the backing film, and sealing it in an aluminum-plastic bag. Using method is the same as embodiment 1.

The results of in vitro transdermal test showed that the cumulative release amount of the patch could reach 44.48 μg/cm ² in 24 hours.

Embodiment 6 sheep placenta anti-wrinkle transdermal patch

1. Drug storage formula:

2. Patch preparation:

Add polyvinyl alcohol, artemisia gum, sorbitol, zinc oxide, zinc oxide, and micropowder silica gel into water, stir and mix evenly. Add sheep placenta freeze-dried powder, and mechanically stir to make it evenly mixed. Coat 1mm on the protective film. Cover the backing film, press it tightly, cut it, bond the graphene oxide electric heating film on the backing film, and store it in an aluminum-plastic bag. Using method is the same as embodiment 1.

The results of in vitro transdermal test showed that the cumulative release amount of the patch could reach 26.17μg/cm ² in 24 hours.

Apparently, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those of ordinary skill in the art can also make It is impossible to exhaustively list all the implementation modes here, and any obvious changes or changes derived from the technical solutions of the present invention are still within the scope of protection of the present invention.

Claims (6)

1. The utility model provides a graphite oxide electric heat membrane transdermal patch which characterized in that, graphite oxide electric heat membrane transdermal patch from the top down includes in proper order: the graphene oxide electrothermal film, a backing film, a drug storage and a protective film;

the graphene oxide electric heating film is heated by being communicated with a power supply, and the acting temperature is 40-45 ℃;

the drug storage formula is as follows: diclofenac sodium 2.4 g, DURO-TAK 87-2677 medical pressure-sensitive adhesive 76.3g, ethanol 20g, boric acid 1.3 g;

the patch is prepared according to the following method:

adding diclofenac sodium into ethanol, uniformly mixing, adding lactic acid to dissolve the diclofenac sodium, adding DURO-TAK 87-2677 medical pressure-sensitive adhesive, magnetically stirring at a constant temperature of 60 ℃ for 1 hour, standing for 1 hour to remove air bubbles, coating on a protective film, wherein the coating thickness is 300 mu m, drying at 70 ℃ for 20min, covering a backing film, compacting, cutting, bonding a graphene oxide electrothermal film on the backing film, and sealing and storing an aluminum plastic bag;

the DURO-TAK 87-2677 medical pressure-sensitive adhesive contains 39.5% of acrylate and vinyl acetate copolymer, 22.4% of ethyl acetate, 22.4% of isopropanol, 12.7% of heptane and 3% of toluene.

2. The graphene oxide electrothermal film transdermal patch according to claim 1, wherein the graphene oxide electrothermal film is detachably adhered to a backing film.

3. The graphene oxide electrothermal film transdermal patch according to claim 1, wherein the graphene oxide electrothermal film can be detachably bonded to the backing film by means of heat-resistant glue.

4. The graphene oxide electrothermal film transdermal patch according to claim 1, wherein the graphene oxide electrothermal film comprises a graphene oxide conductive layer and an insulating protective layer.

5. The graphene oxide electrothermal film transdermal patch according to claim 4, wherein the insulating protective layer is made of one or a mixture of two of polyimide and polyethylene terephthalate.

6. The graphene oxide electrothermal film transdermal patch according to claim 1, wherein the content of the drug in the graphene oxide electrothermal film transdermal patch per square centimeter is in a range of 0.2-2mg.

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