CN109481422B - Graphene oxide electrothermal film transdermal patch - Google Patents
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M2037/0007—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
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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
Technical Field
The invention relates to the technical field of medicines. More particularly, relates to a graphene oxide electrothermal film transdermal patch.
Background
Compared with the traditional administration mode, the transdermal administration technology has many advantages, avoids the first pass effect of the liver on the medicine and the decomposition of the gastrointestinal tract, and improves the treatment effect; relatively stable blood concentration is maintained, peak valley phenomenon is avoided, and side effect is reduced; prolongs the administration time, reduces the administration times and improves the compliance of patients. These unique advantages have attracted many pharmaceutical industry sectors to develop new transdermal formulations.
The skin can play a barrier role in percutaneous absorption of medicines, and particularly the stratum corneum of the outermost layer of the skin in a brick wall structure. The medicine can protect the body from being invaded by foreign matters and simultaneously play a role of a speed-limiting barrier for any medicine molecule. In order to increase the amount of drug that permeates transdermally, new methods of enhancing transdermal delivery are emerging. The use of chemical skin enhancers can increase passive transdermal penetration of small molecule drugs, failing to overcome the size limitation of large molecule drugs. Another common drawback of penetration enhancers is that they tend to cause skin irritation as they increase the transdermal permeability of the drug by interfering with the ordered stratum corneum lipid bilayers or keratinocyte structures.
Physical permeation-promoting techniques employ a combination of devices to increase drug transdermal permeability, such as active drug delivery techniques that promote drug permeability with the aid of external energy, including pressure-driven fluidics, iontophoretic skin patches, microneedles, lasers, and heat. Plays a great role in promoting the widening of the variety of the drugs applicable to the field of transdermal drug delivery.
The development of various materials as drug carriers has been promoted by the achievements in material science and nanotechnology. Particularly, graphene-based materials have attracted great attention in this field due to their high loading capacity, using external stimuli such as pH, electricity, electrochemistry, light, etc. to initiate drug release in graphene matrix. For drugs that require long-term release, thermal permeation promotion is an effective method. Due to the excellent performance of graphene oxide, the graphene oxide has a good application prospect in the fields of heat conduction and dissipation materials, electric heating films, catalyst carriers and the like, and the attention of the graphene oxide in the field of drug release is higher and higher. In the research of graphene oxide as a drug carrier, it is found that driving the release of the drug by the electrothermal effect generated by electric excitation is one of the most effective ways. Thermally controlled drug delivery systems typically trigger the drug release of the carrier by heat. The transdermal permeation rate of the drug can be controlled by heat-activated patches, which provides a solution for long-term control of the release of the active ingredient.
The conventional thermal therapy method generally heats a carrier such as volcanic mud compress, heat-storing gel and the like in advance as a latent heat storage body, or releases heat through an oxidation process of iron powder. In addition, capsaicin can be added to the patch to stimulate the skin and produce subjective heat sensation.
However, the above methods have common disadvantages in that heat supply cannot be controlled, the temperature of action cannot be precisely adjusted, and heating that is continuously stable for a long time cannot be achieved. And the exothermic substance is integrated into the patch, the heat supply cannot be interrupted without removing the patch from the patient's skin.
Disclosure of Invention
The invention aims to provide a graphene oxide electrothermal film transdermal patch which can controllably output heat through an electrothermal effect generated by electrically exciting a graphene oxide film, promote the release of a medicament, improve the transdermal permeation quantity of the medicament and have a good treatment effect.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides 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.
Further, the graphene oxide electrothermal film is heated by being communicated with a power supply, and the action temperature is 35-50 ℃, preferably 40-45 ℃.
Further, the graphene oxide electrothermal film is detachably bonded on the backing film, and preferably can be bonded through heat-resistant glue.
Further, the graphene oxide electrothermal film comprises a graphene oxide conducting layer and an insulating protective layer.
Further, the insulating protective layer is made of one or a mixture of two of polyimide and polyethylene terephthalate, and the resistance of the insulating protective layer is 2-20 omega.
Further, the drug reservoir is a hydrogel or a pressure sensitive adhesive patch.
Further, the raw materials of the hydrogel agent comprise raw material medicines, a high-molecular framework material, a humectant and an adhesiveAnd a filler. The preparation method of the graphene oxide electrothermal film transdermal patch with the hydrogel as the drug reservoir generally comprises the following steps: mixing the above materials, adding into water, stirring, dispersing, standing to remove air bubbles to obtain unguent, coating onto the protective layer with a thickness of 0.1-2mm, preferably 0.3-1mm, covering with backing film, pressing, cutting into pieces with area of 5-100cm 2 And (3) bonding the graphene oxide electrothermal film on the backing film to obtain the patch.
Preferably, the polymer skeleton material includes but is not limited to one or more of acrylate, polyvinyl alcohol, gelatin, sodium polyacrylate, cellulose derivative, chitosan derivative, polyvinylpyrrolidone and artemisia seed gum; the adhesive includes, but is not limited to, polyacrylic acid and its sodium salt. The humectant includes: one or more of glycerol, propylene glycol and sorbitol; the filler includes, but is not limited to, one or more of micropowder silica gel, calcium carbonate, kaolin, bentonite, titanium dioxide, zinc oxide and talcum powder.
Further, the raw materials of the pressure-sensitive adhesive patch comprise raw material medicines, pressure-sensitive adhesive and solubilizer. The preparation method of the graphene oxide electrothermal film transdermal patch with the drug reservoir as the pressure-sensitive adhesive patch generally comprises the following steps: mixing the raw materials, adding the mixture into the pressure-sensitive adhesive, stirring and mixing uniformly, standing for 1 hour to remove bubbles to obtain a medicine-containing adhesive solution; coating the medicinal glue solution on the protective layer at a certain thickness of 300-600 μm, drying at 70-90 deg.C for 10-20min, oven drying, taking out the backing film, pressing, and cutting into pieces with area of 5-100cm 2 And (3) bonding the graphene oxide electrothermal film on the backing film to obtain the patch.
Preferably, the pressure-sensitive adhesive is acrylate pressure-sensitive adhesive or polyisobutylene pressure-sensitive adhesive according to the property of the raw material medicine; the solubilizer includes but is not limited to one or a mixture of more of lactic acid, sodium lactate, boric acid, citric acid and tartaric acid.
Further, the raw material drugs can be active ingredients of cosmetics and drugs, and the raw material drugs in the pressure-sensitive adhesive patch and the hydrogel are selected according to the properties of the raw material drugs, and specifically include but are not limited to one or a mixture of more of pain-relieving active ingredients, fat-reducing active ingredients, scar-removing active ingredients, whitening active ingredients and rheumatism and rheumatoid drugs. Preferably, the analgesic active ingredient includes, but is not limited to, acetaminophen, non-steroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen, aspirin, fenoprofen, flurbiprofen, ketoprofen, oxaprozin (oxaprozin), diclofenac sodium, etodolac, indomethacin ketorolac, tolmetin meclofenamate sulindate, mefenamic acid, nabumetone piroxicam, COX-2 inhibitors, etc.), corticosteroids (e.g., cortisone), anesthetics, anticonvulsants (e.g., gabapentin, pregabalin), local anesthetics (e.g., antihistamines such as diphenhydramine hydrochloride, chlorpheniramine maleate, anesthetic such as sodium pentobarbital), etc.; the fat-reducing effective components include but are not limited to L-carnitine, orlistat and dimethyl biguanide; effective scar-removing components including, but not limited to triamcinolone acetonide acetate, lumbricus polypeptide, carnosine, asiaticoside, hirudin, and ginsenoside; the whitening active ingredients include, but are not limited to, ascorbic acid, magnesium ascorbyl phosphate, tranexamic acid, ascorbyl glucoside (ascorbyl glucoside), ascorbyl palmitate, licorice extract, yeast extract, trametes (trametes), aspergillus (aspergillus), exophium (exophilia), resveratrol and derivatives resveratrol phosphate, resveratrol ferulate, oxyresveratrol, ferulic acid and derivatives thereof, azelaic acid derivatives, kojic acid, ellagic acid, hinokitiol, soybean extract, scutellaria extract, mulberry extract, molasses, tetrahydrocurcumin, glycyrrhetinic acid, refined niacinamide, pomegranate, grape seed extract, lupulus weifen, BV-OSC-tetrahexyldecanol ascorbate, disodium ascorbyl hydrogen phosphate, ascorbyl glucoside, alpha (beta) -arbutin, ascorbyl palmitate, resorcinol, and tranexamic acid; the rheumatism and rheumatoid medicine includes but is not limited to diclofenac sodium, diclofenac diethylamine, anluotong, radix et rhizoma Rhei Franch, carthami flos extract, sanguis Draxonis extract, radix Clematidis extract, herba Lycopodii extract, etc.; the anti-wrinkle effective component includes, but is not limited to, ovine placenta, retinol acetate, vitamin A palmitate, retinoic acid, vitamin A acetate, vitamin C and derivatives thereof.
Preferably, the content range of the raw material medicine in the graphene oxide electrothermal film transdermal patch per square centimeter is 0.2-2mg.
Further, the backing film is one or more layers of composite films, and the material of the backing film comprises one or more of polyethylene terephthalate, polypropylene, polyethylene, ethylene-vinyl acetate copolymer and polyurethane.
Further, the thickness of the backing film is 30-300 μm.
Further, the material of the protective film is one or a mixture of a plurality of polyethylene terephthalate, polyethylene and polypropylene films, the surfaces of which are subjected to plasma treatment and fluorine or silicon coating treatment, and the polyethylene terephthalate is preferably subjected to fluorine coating treatment.
Further, the thickness of the protective film is 20-300 μm.
The invention has the following beneficial effects:
1. 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.
2. The graphene oxide electrothermal film transdermal patch can controllably output heat and accurately regulate temperature, and can realize long-time continuous and stable heating, so that the administration dosage is more accurate.
3. The graphene oxide electrothermal film transdermal patch is detachably bonded, so that timely heat supply interruption and electrothermal film recycling can be realized.
Drawings
The following describes embodiments of the present invention in further detail with reference to the accompanying drawings.
Fig. 1 is a schematic side view of a graphene oxide electrothermal film transdermal patch according to the present invention; wherein, the structure comprises 1-graphene oxide electrothermal film, 2-backing film, 3-drug storage and 4-protective film.
Fig. 2 shows a 3.5mm circular graphene oxide electrothermal film: A. a graphene oxide electric heating film object diagram; B. and (3) a thermal imager diagram of the graphene oxide electrothermal film.
Figure 3 shows the cumulative release (absolute) for 24h for the patch of the formulation of example 1: a. attaching an electric heating film at 45 ℃; b. attaching an electric heating film for heating at 40 ℃; c. heating the attached electrothermal film at 50 ℃; d. the electric heating film is not attached.
Fig. 4 shows the relation between the measurement temperature and the voltage and the resistance when the graphene oxide electrothermal film is attached to the surface of the skin.
Fig. 5 shows observation of histopathology section after the graphene oxide electrothermal film is attached to the surface of human skin and heated: A. normal skin; B. the graphene oxide electric heating film acts for 24 hours at 40 ℃; C. the graphene oxide electrothermal film is acted for 24 hours at 45 ℃; D. the graphene oxide electrothermal film is acted for 24 hours at 50 ℃.
Detailed Description
In order to more clearly illustrate the invention, the invention is further described below with reference to preferred embodiments and the accompanying drawings. Similar parts in the figures are denoted by the same reference numerals. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.
The invention provides 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.
Further, the graphene oxide electrothermal film is heated by connecting a power supply, and the action temperature is 35-50 ℃, preferably 40-45 ℃, and can be 35 ℃,40 ℃,45 ℃,50 ℃ and the like. The invention realizes long-time continuous and stable heating by controllably outputting heat and accurately adjusting temperature, thereby ensuring that the administration dosage is more accurate.
Further, the graphene oxide electrothermal film is detachably bonded on the backing film, and preferably can be bonded through heat-resistant glue. The protective layer is torn off during use, the medicine storehouse is pasted on skin, and the power supply graphene oxide electrothermal film is communicated to maintain a proper temperature, so that the medicine is promoted to penetrate through skin, the treatment effect is enhanced, and timely interruption of heat supply and reuse of the electrothermal film can be realized.
Further, the graphene oxide electrothermal film comprises a graphene oxide conducting layer and an insulating protective layer.
Further, the material of the insulating protective layer is one or a mixture of two of polyimide and polyethylene terephthalate, and the resistance of the insulating protective layer is 2-20 omega.
Further, the drug reservoir is a hydrogel or a pressure sensitive adhesive patch.
Further, the raw materials of the hydrogel agent comprise a raw material drug, a high-molecular framework material, a humectant, a tackifier and a filler. The preparation method of the graphene oxide electrothermal film transdermal patch with the hydrogel as the drug reservoir generally comprises the following steps: mixing the raw materials, adding into water, stirring, dispersing, standing to remove air bubbles to obtain unguent, coating unguent on the protective layer at a certain thickness of 0.1-2mm, preferably 0.3-1mm to cover backing film, pressing, and cutting into pieces with area of 5-100cm 2 And (3) bonding the graphene oxide electrothermal film on the backing film to obtain the patch.
Preferably, the polymer framework material includes but is not limited to one or more of acrylate, polyvinyl alcohol, gelatin, sodium polyacrylate, cellulose derivative, chitosan derivative, polyvinylpyrrolidone and artemisia seed gum; the adhesive includes, but is not limited to, polyacrylic acid and its sodium salt. The humectant includes: one or more of glycerol, propylene glycol and sorbitol; the filler includes but is not limited to micropowder silica gel, calcium carbonate, kaolin, bentonite, titanium dioxide, zinc oxide and one or more mixtures of talcum powder.
Further, the raw materials of the pressure-sensitive adhesive patch comprise raw material medicines, pressure-sensitive adhesive and solubilizer. The preparation method of the graphene oxide electrothermal film transdermal patch with the drug reservoir as the pressure-sensitive adhesive patch generally comprises the following steps: mixing the raw materials, adding into pressure sensitive adhesive, stirring, standing for 1 hr to remove air bubbles to obtain medicine-containing materialGlue solution; coating the medicinal glue solution on the protective layer at a certain thickness of 300-600 μm, drying at 70-90 deg.C for 10-20min, oven drying, taking out the backing film, compacting, and cutting into pieces with area of 5-100cm 2 And (3) bonding the graphene oxide electrothermal film on the backing film to obtain the patch.
Preferably, the pressure-sensitive adhesive is acrylate pressure-sensitive adhesive or polyisobutylene pressure-sensitive adhesive according to the property of the raw material medicine; the solubilizer includes but is not limited to one or a mixture of more of lactic acid, sodium lactate, boric acid, citric acid and tartaric acid. The solubilizer can effectively increase the solubility of the raw material medicaments in the pressure-sensitive adhesive.
Further, the raw material medicines can be effective components of cosmetics and medicines, and the raw material medicines in the pressure-sensitive adhesive patch and the hydrogel are selected according to the properties of the raw material medicines, and specifically include but are not limited to one or a mixture of more of pain-relieving effective components, fat-reducing effective components, scar-removing effective components, whitening effective components and rheumatism and rheumatoid medicines. Preferably, the analgesic active ingredient includes, but is not limited to, acetaminophen, non-steroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen, aspirin, fenoprofen, flurbiprofen, ketoprofen, oxaprozin (oxaprozin), diclofenac sodium, etodolac, indomethacin ketorolac, tolmetin meclofenamate sulindate, mefenamic acid, nabumetone piroxicam, COX-2 inhibitors, etc.), corticosteroids (e.g., cortisone), anesthetics, anticonvulsants (e.g., gabapentin, pregabalin), local anesthetics (e.g., antihistamines such as diphenhydramine hydrochloride, chlorpheniramine maleate, anesthetic such as sodium pentobarbital), etc.; the fat-reducing effective components include but are not limited to L-carnitine, orlistat and dimethyl biguanide; effective scar-removing components including, but not limited to triamcinolone acetonide acetate, lumbricus polypeptide, carnosine, asiaticoside, hirudin, and ginsenoside; the whitening active ingredients include, but are not limited to, ascorbic acid, magnesium ascorbyl phosphate, tranexamic acid, ascorbyl glucoside (ascorbyl glucoside), ascorbyl palmitate, licorice extract, yeast extract, trametes (trametes), aspergillus (aspergillus), exophium (exophilia), resveratrol and derivatives resveratrol phosphate, resveratrol ferulate, oxyresveratrol, ferulic acid and derivatives thereof, azelaic acid derivatives, kojic acid, ellagic acid, hinokitiol, soybean extract, scutellaria extract, mulberry extract, molasses, tetrahydrocurcumin, glycyrrhetinic acid, refined niacinamide, pomegranate, grape seed extract, lupulus weifen, BV-OSC-tetrahexyldecanol ascorbate, disodium ascorbyl hydrogen phosphate, ascorbyl glucoside, alpha (beta) -arbutin, ascorbyl palmitate, resorcinol, and tranexamic acid; the rheumatism and rheumatoid medicine includes but is not limited to diclofenac sodium, diclofenac diethylamine, anluotong, radix et rhizoma Rhei Franch, carthami flos extract, sanguis Draxonis extract, radix Clematidis extract, herba Lycopodii extract, etc.; the anti-wrinkle effective component includes, but is not limited to, ovine placenta, retinol acetate, vitamin A palmitate, retinoic acid, vitamin A acetate, vitamin C and derivatives thereof.
Preferably, the content range of the raw material medicine in the graphene oxide electrothermal film transdermal patch per square centimeter is 0.2-2mg. For example, it may be 0.2mg, 0.5mg, 1mg, 1.5mg, 2mg, etc.
Further, the backing film is one or more layers of composite films, and the material of the backing film comprises one or more of polyethylene terephthalate, polypropylene, polyethylene, ethylene-vinyl acetate copolymer and polyurethane.
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, or the like.
Further, the material of the protective film is one or a mixture of a plurality of polyethylene terephthalate, polyethylene and polypropylene films, the surfaces of which are subjected to plasma treatment and fluorine or silicon coating treatment, and the polyethylene terephthalate is preferably subjected to fluorine coating treatment.
Further, the thickness of the protective film is 20-300 μm. For example, it may be 20 μm, 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, or the like.
The present invention will be further described below by way of specific examples.
In the present invention, the raw materials and equipment used are commercially available or commonly used in the art, unless otherwise specified. The methods in the following examples are conventional in the art unless otherwise specified.
EXAMPLE 1 diclofenac sodium analgesic transdermal Patch
1. The drug reservoir formulation:
2. patch preparation
Adding diclofenac sodium into ethanol, uniformly mixing, adding lactic acid to dissolve the diclofenac sodium, adding DURO-TAK 87-2677 medical pressure-sensitive adhesive (containing 39.5 percent of acrylate and vinyl acetate copolymer, 22.4 percent of ethyl acetate, 22.4 percent of isopropanol, 12.7 percent of heptane and 3 percent of methylbenzene), magnetically stirring at the constant temperature of 60 ℃ for 1 hour, standing for 1 hour to remove air bubbles, coating on a protective film with the coating thickness of 300 mu m, drying at 70 ℃ for 20 minutes, covering a backing film, pressing, cutting, adhering a graphene oxide electrothermal film on the backing film, and sealing and storing an aluminum plastic bag.
Tearing the protection film during the use, medicine storehouse layer is pasted on skin, and the heating of oxidation graphite alkene electric heat membrane intercommunication power finishes, takes off oxidation graphite alkene electric heat membrane reuse.
The graphene oxide electrothermal film transdermal patch obtained in the embodiment is subjected to an in-vitro transdermal experiment on pig ear skin: the skin of the pig ear was mounted on the diffusion cell using a modified Franz diffusion cell, with the dermis facing the receiving chamber and the stratum corneum facing the feeding chamber. The patch is pasted on the stratum corneum layer, a proper amount of phosphate buffer solution with pH =7.4 is added in a receiving chamber, samples are taken after being circulated in a thermostatic water bath at 37 ℃ and being magnetically stirred for 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours, the concentration of the samples is measured by high performance liquid chromatography, the result is shown in figure 3, and the obvious permeation promoting effect can be seen by utilizing the heating of the graphene oxide electrothermal film. The graphene oxide electrothermal film is attached to the surface of the skin, two electrodes are connected with the output end of a direct current stabilized power supply, and the relationship between the measured temperature and the voltage and the resistance is shown in fig. 4. The electrothermal film can maintain the skin surface at 48 ℃ at most in the voltage range of 0-2.5V. The results of the observation of tissue paraffin section HE staining are shown in figure 5, and it can be seen that the normal skin stratum corneum and epidermis are intact, have no damage, and have abundant muscle fibers, and the stratum corneum of the skin can be loosened by heating at 40 ℃ and 45 ℃ to facilitate the penetration of the drug through the skin, and the transdermal permeation amount is the highest at 45 ℃ to improve the transdermal permeability of the patch by 4.2 times, and the heating at 50 ℃ can have a certain destructive effect on the stratum corneum.
EXAMPLE 2L-Carnitine lipid-reducing transdermal Patch
1. The drug reservoir formulation:
2. preparation of the patch:
adding sodium carboxymethylcellulose, artemisia desertorum gum, glycerol, silica gel micropowder and Kaolin into water, stirring and mixing. Adding L-carnitine, and mechanically stirring to mix them uniformly. The protective film was coated to a thickness of 500. Mu.m. Covering a backing film, compacting, cutting, bonding a graphene oxide electrothermal film on the backing film, and sealing and storing the aluminum plastic bag. The procedure was as in example 1.
The result of in vitro transdermal experiment shows that the 24-hour accumulated release amount of the patch can reach 39.71 mu g/cm 2 。
Example 3 triamcinolone acetonide acetate scar-removing transdermal patch
1. The drug storage formula is as follows:
triamcinolone acetonide acetate 3g
DURO-TAK 387-2510 medical pressure-sensitive adhesive 77g
20g of glycerol
2. Preparation of the patch:
glycerol and triamcinolone acetonide acetate are added into DURO-TAK 387-2510 medical pressure-sensitive adhesive (containing 40.5 percent of acrylate polymer, 54.1 percent of ethyl acetate and 5.4 percent of hexane), and the mixture is magnetically stirred and uniformly mixed at the constant temperature of 60 ℃ to be completely dissolved. Standing for 1 hour, and removing bubbles. Coating a protective film with a thickness of 600 micrometers, drying for 10min at 90 ℃, 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 procedure was as in example 1.
The results of in vitro transdermal experiments show that the 24-hour accumulated release amount of the patch can reach 23.83 mug/cm 2 。
Example 4 ascorbic acid whitening transdermal patch
1. The drug storage formula is as follows:
2. preparation of the patch:
adding polyvinylpyrrolidone, polyethylene glycol, propylene glycol and calcium carbonate into water, and stirring and mixing uniformly. Ascorbic acid was added and mixed well by mechanical stirring. The protective film was coated with 1mm. Covering a backing film, compacting, cutting, bonding a graphene oxide electrothermal film on the backing film, and sealing and storing the aluminum plastic bag. The method of use is the same as in example 1.
The results of in vitro transdermal experiments show that the 24-hour accumulated release amount of the patch can reach 28.59 mug/cm 2 。
Example 5 diclofenac diethylamine rheumatism transdermal patch
1. The drug storage formula is as follows:
2. patch preparation
Adding diclofenac diethylamine into ethanol, uniformly mixing, adding sodium lactate to promote the dissolution of diclofenac diethylamine, 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 bubbles, coating on a protective film, coating to a thickness of 200 μm, drying at 80 ℃ for 15min, covering with a backing film, compacting, cutting, adhering a graphene oxide electrothermal film on the backing film, and sealing and storing with an aluminum plastic bag. The method of use is the same as in example 1.
The result of in vitro transdermal experiment shows that the 24-hour accumulated release amount of the patch can reach 44.48 mu g/cm 2 。
Example 6 anti-wrinkle transdermal patch of sheep placenta extract
1. The drug storage formula is as follows:
2. preparation of the patch:
adding polyvinyl alcohol, artemisia desertorum gum, sorbitol, zinc oxide, and silica gel micropowder into water, stirring, and mixing. Adding lyophilized powder of foetus Caprae Seu Ovis extract, and mechanically stirring to mix well. The protective film was coated with 1mm. Covering a backing film, compacting, cutting, bonding a graphene oxide electrothermal film on the backing film, and sealing and storing the aluminum plastic bag. The method of use is the same as in example 1.
The result of in vitro transdermal experiment shows that the 24-hour accumulated release amount of the patch can reach 26.17 mu g/cm 2 。
It should be understood that the above-described embodiments of the present invention are examples for clearly illustrating the invention, and are not to be construed as limiting the embodiments of the present invention, and it will be obvious to those skilled in the art that various changes and modifications can be made on the basis of the above description, and it is not intended to exhaust all embodiments, and obvious changes and modifications can be made on the basis of the technical solutions 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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