Composite medicine-carrying navel therapy patch based on PU (polyurethane) film and preparation method of composite medicine-carrying navel therapy patch

Abstract

The invention belongs to the technical field of traditional Chinese medicine navel patches, and particularly relates to a composite medicine carrying navel therapy patch based on a PU film and a preparation method thereof.The composite medicine carrying navel therapy patch comprises an anti-sticking release film, a medicine carrying layer, a medical pressure-sensitive adhesive layer and a PU waterproof protective layer; the traditional Chinese medicine extract is prepared from the following raw materials in parts by weight: 10 to 20 parts of rhizoma zingiberis, 10 to 15 parts of roasted rhizoma atractylodis macrocephalae, 8 to 12 parts of radix codonopsis, 5 to 10 parts of fructus evodiae, 5 to 10 parts of fructus foeniculi, 3 to 8 parts of cortex cinnamomi, 1 to 3 parts of borneol, 8 to 20 parts of polysorbate 80, 0.5 to 2 parts of carbomer 940, 1 to 3 parts of triethanolamine and 0.1 to 0.5 part of EDTA-2Na. By means of the integrated design of slow-release hydrogel drug loading and the multi-layer patch, efficient transdermal absorption and stable release of drugs are achieved, and the bioavailability and application comfort of the composite drug-loading navel therapy patch are improved.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a composite drug-loaded umbilical patch based on a PU film and its preparation method. Background Technology

[0002] Umbilical therapy is a unique external treatment method in Traditional Chinese Medicine (TCM) that has been passed down for thousands of years. Its basis lies in the fact that the skin of the Shenque acupoint (the navel) is thin and delicate, with a dense capillary network and good permeability. Furthermore, it is connected to internal organs through meridians, making it an ideal site for transdermal drug delivery. Traditional umbilical therapy often involves grinding Chinese medicinal herbs into coarse powder, mixing it with vinegar, wine, or honey to form a paste, applying it directly to the navel, covering it with gauze, and securing it with adhesive tape.

[0003] However, the dosage form of this traditional umbilical therapy is relatively outdated, with crude drug forms, often remaining at the powder or simple extract stage. This results in low concentrations of active ingredients, requiring large doses to achieve therapeutic effects, but with limited transdermal absorption efficiency and low bioavailability. The content of active ingredients fluctuates significantly due to the source of the medicinal materials, processing methods, and extraction processes, leading to unstable product quality and difficulty in guaranteeing and replicating efficacy. Furthermore, the medicinal materials often contain impurities such as starch, fiber, and tannins, which can easily irritate the local skin, causing adverse reactions such as allergies, redness, swelling, and itching, thus affecting safety.

[0004] Furthermore, traditional application methods are rudimentary, with the drug-carrying layer mostly having a planar structure, which is extremely poorly adapted to the concave physiological structure of the navel. This makes it impossible to achieve a complete and tight fit with the skin of the navel, resulting in a large number of gaps. This not only significantly reduces the effective contact area between the drug and the Shenque acupoint, but also causes the loss of drug components, further reducing the transdermal absorption efficiency. At the same time, it is easy to shift and fall off, and the drug is easy to seep out and stain clothing. Moreover, the ointment is easy to dry and lose its activity, making it inconvenient to store and use, resulting in a poor patient experience and low treatment compliance.

[0005] Therefore, developing a novel umbilical therapy patch that enables stable and efficient release of active pharmaceutical ingredients, while improving drug concentration and transdermal efficiency and ensuring safety, and further enhancing the convenience, comfort, and hygiene of application, has clear clinical significance and application value. Summary of the Invention

[0006] To address the shortcomings of the existing technology, this invention provides a composite drug-loaded umbilical patch based on a PU film and its preparation method. The composite drug-loaded umbilical patch uses traditional Chinese medicine active ingredients with warming and dispelling cold, and invigorating the spleen and replenishing qi as the core, which are encapsulated in a sustained-release hydrogel and further coated in a multi-layer integrated patch. This achieves efficient transdermal absorption and stable release of traditional Chinese medicine active ingredients, significantly improving the bioavailability, safety, and comfort of the composite drug-loaded umbilical patch.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] This invention provides a composite drug-loaded umbilical patch based on a PU film, which consists of, from top to bottom, an anti-adhesive release film, a drug-loaded pressure-sensitive layer, and a PU (polyurethane) waterproof protective layer.

[0009] Furthermore, the drug-loaded pressure-sensitive layer includes a medical pressure-sensitive adhesive and a drug-loaded layer.

[0010] Furthermore, the drug-carrying layer is prepared by coating a carrier matrix with a traditional Chinese medicine extract.

[0011] Furthermore, the drug-carrying layer is a hemispherical structure conforming to the shape of the navel;

[0012] Furthermore, the coating dosage of the herbal extract is 1.5 parts.

[0013] Furthermore, the carrier matrix is ​​a PU sponge molded into a hemispherical shape.

[0014] Furthermore, the herbal extract comprises the following raw materials in parts by weight: 10-20 parts dried ginger, 10-15 parts stir-fried Atractylodes macrocephala, 8-12 parts Codonopsis pilosula, 5-10 parts Evodia rutaecarpa, 5-10 parts fennel, 3-8 parts cinnamon, 1-3 parts borneol, 8-20 parts polysorbate 80, 0.5-2 parts carbomer 940, 1-3 parts triethanolamine, and 0.1-0.5 parts EDTA-2Na (disodium ethylenediaminetetraacetate).

[0015] Furthermore, the preparation method of the traditional Chinese medicine extract includes the following steps:

[0016] S1: Weigh 5-10 parts of fennel seeds and 3-8 parts of cinnamon, crush them separately and sieve them, mix them evenly to obtain mixed volatile oil medicinal materials, extract them by steam distillation for 6 hours, collect the distillate, let it stand and separate the layers, separate the upper and lower layers to obtain mixed volatile oil and aromatic water respectively, combine the aromatic water with the distillation residue to obtain the remaining mixture;

[0017] S2: Weigh 10-20 parts of dried ginger, 10-15 parts of stir-fried Atractylodes macrocephala, 8-12 parts of Codonopsis pilosula and 5-10 parts of Evodia rutaecarpa, crush them separately and sieve them, combine them with the remaining mixture, add purified water, mix evenly to obtain a water-extracted mixture, soak, decoct twice, filter to obtain decoction filtrate.

[0018] S3: Concentrate the decoction filtrate under reduced pressure to a relative density of 1.10-1.15, add 95% ethanol (volume fraction) to make the alcohol content reach 65%, let stand, collect the supernatant, filter, and concentrate again under reduced pressure to a relative density of 1.25-1.30 to obtain a refined thick paste.

[0019] S4: Weigh 1-3 parts of borneol, grind it into a fine powder and sieve it. Add 8-20 parts of mixed volatile oil and nonionic surfactant polysorbate 80 to it, emulsify for 5 minutes to obtain volatile oil emulsion, add refined thick paste to it, mix evenly to obtain traditional Chinese medicine emulsion thick paste.

[0020] S5: Weigh 0.5-2 parts of Carbomer 940 and disperse it in purified water to obtain a carbomer gel matrix. While stirring, add the traditional Chinese medicine emulsion to it, add 1-3 parts of triethanolamine to adjust the pH to 6.0-6.5, and then add 0.1-0.5 parts of stabilizer EDTA-2Na. After vacuum degassing and homogenization, the traditional Chinese medicine extract is obtained.

[0021] Furthermore, the medical pressure-sensitive adhesive is selected from any one of silicone gel pressure-sensitive adhesive, hydrocolloid pressure-sensitive adhesive, and acrylate pressure-sensitive adhesive.

[0022] Furthermore, the preparation method of the drug-loaded pressure-sensitive layer is as follows: after preparing the drug-loaded layer into a hemispherical shape, it is placed in a mold, and medical pressure-sensitive adhesive is filled into the area outside the drug-loaded layer in the mold to form a drug-loaded pressure-sensitive layer with the drug-loaded layer in the center and the medical pressure-sensitive adhesive in the surrounding area.

[0023] Furthermore, the anti-stick release film is made of glassine paper treated with silicone oil and has a groove structure adapted to the shape of the drug-loaded layer.

[0024] Furthermore, the PU waterproof protective layer uses a medical-grade PU film.

[0025] This invention also provides a method for preparing a composite drug-loaded umbilical patch based on a PU film, specifically including the following steps:

[0026] Step 1: Place the drug-loaded pressure-sensitive layer on the PU waterproof protective layer and bond it by hot pressing to obtain a layered composite substrate;

[0027] Step 2: Take the anti-adhesive release film and cover it on the layered composite substrate. Roll press to make each layer adhere tightly to obtain the finished patch. Encapsulate the finished patch to obtain the PU film-based composite drug-loaded umbilical therapy patch.

[0028] The beneficial effects achieved by this invention are as follows:

[0029] This invention prepares a PU-film-based composite drug-loaded umbilical patch that uses traditional Chinese medicine extracts as active ingredients for transdermal drug delivery. It selects herbs such as dried ginger, stir-fried Atractylodes macrocephala, and Codonopsis pilosula, which are warming and dispelling cold, and invigorating the spleen and replenishing qi. These are combined with fennel, cinnamon, and Evodia rutaecarpa to regulate qi and relieve pain, and borneol is added to promote transdermal absorption. The overall formula combines the comprehensive effects of warming yang, invigorating the spleen, regulating qi, and relieving pain. The extracts of these herbs are combined with polysorbate and carbomer gel matrix to form a sustained-release hydrogel. This not only improves drug stability and compatibility but also enables continuous and stable drug release, increasing transdermal absorption efficiency while reducing skin irritation. This addresses the problems of unstable release and strong irritation associated with traditional Chinese medicine umbilical patches.

[0030] In terms of patch structure, this invention designs the drug-carrying layer as a hemispherical structure that conforms to the shape of the navel, completely filling and closely contacting the Shenque acupoint. This significantly increases the contact area between the drug and the skin, reduces drug loss, and thus further improves transdermal absorption efficiency and therapeutic effect. Employing a multi-layer integrated design, the outer PU film is soft, breathable, waterproof, and moisture-proof, effectively blocking sweat and maintaining a stable local microenvironment. The middle medical pressure-sensitive adhesive ensures a firm fit, preventing displacement or detachment during use. The carrier matrix combined with sustained-release hydrogel ensures uniform drug distribution and controlled release. The anti-adhesive release film facilitates storage and retrieval. Each layer has a clear function and complements each other, improving adhesion comfort, preventing drug contamination, and ensuring continuous and stable drug release locally, achieving synergistic optimization of structure, function, and efficacy.

[0031] The PU film-based composite drug-loaded umbilical therapy patch provided by this invention, through the optimization of traditional Chinese medicine compatibility, gel sustained-release drug loading technology and multi-layer composite structure design, forms a highly efficient, safe and convenient composite drug-loaded umbilical therapy patch, which has high clinical application value and industrialization prospects. Attached Figure Description

[0032] Figure 1 This is an exploded structural diagram of a composite drug-loaded umbilical patch based on a PU film according to the present invention.

[0033] Figure 2 The results of in vitro transdermal absorption tests of the composite drug-loaded umbilical patches prepared in Examples 1-3 and Comparative Examples 1-3;

[0034] Figure 3 The results of pharmacodynamic tests on rats of the composite drug-loaded umbilical patch prepared in Example 1 and Comparative Examples 1-3 are shown.

[0035] Among them, 1. PU waterproof protective layer, 2. Drug-loaded pressure-sensitive layer, 3. Anti-stick release film, 21. Drug-loaded layer, 22. Medical pressure-sensitive adhesive, 211. Traditional Chinese medicine extract, 212. Carrier matrix. Detailed Implementation

[0036] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0037] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0038] The following embodiments show an exploded view of the composite drug-loaded umbilical patch based on a PU film. Figure 1 Unless otherwise specified, all methods are conventional. Unless otherwise specified, all materials used in the following examples are new materials purchased from the market. The Chinese medicinal herbs used, including dried ginger, stir-fried Atractylodes macrocephala, Codonopsis pilosula, Evodia rutaecarpa, fennel, cinnamon, and borneol, are all standard processed medicinal materials according to the Chinese Pharmacopoeia. The materials used in the PU waterproof protective layer, medical pressure-sensitive adhesive layer, carrier matrix, and anti-adhesion release film are all medical grade. The polysorbate 80, carbomer 940, triethanolamine, and EDTA-2Na are all pharmaceutical excipient grade, conforming to the standards of the Chinese Pharmacopoeia. The polysorbate 80 has a viscosity (25℃) of 300-500 mPa·s and an HLB value of approximately 15.0, and is used as an emulsifier and solubilizer. The triethanolamine is a pH adjuster and neutralizer used to activate carbomer to form a gel, with a purity ≥99.0%. The EDTA-2Na is a metal ion chelating agent and stabilizer, with a purity ≥99.0%.

[0039] Example 1: This example provides a composite drug-loaded umbilical patch based on a PU film, which consists of an anti-adhesive release film, a drug-loaded pressure-sensitive layer, and a PU waterproof protective layer from top to bottom.

[0040] The herbal extract comprises the following raw materials in parts by weight: 10 parts dried ginger, 10 parts stir-fried Atractylodes macrocephala, 8 parts Codonopsis pilosula, 5 parts Evodia rutaecarpa, 5 parts fennel, 3 parts cinnamon, 1 part borneol, 8 parts polysorbate, 0.5 parts carbomer 940, 1 part triethanolamine, and 0.1 parts EDTA-2Na.

[0041] The preparation method of the traditional Chinese medicine extract includes the following steps:

[0042] S1: Weigh 5 parts of fennel seeds and 3 parts of cinnamon, grind them separately and pass them through an 80-mesh sieve, mix them evenly to obtain mixed volatile oil medicinal materials, put them into a round-bottom flask, add 50 parts of purified water, extract by steam distillation for 6 hours, collect the distillate, let it stand at 4℃ for 12 hours, collect the upper oil phase to obtain mixed volatile oil, collect the lower aqueous phase to obtain aromatic water, combine the aromatic water with the distillation residue in the round-bottom flask to obtain the remaining mixture;

[0043] S2: Weigh 10 parts dried ginger, 10 parts stir-fried Atractylodes macrocephala, 8 parts Codonopsis pilosula, and 5 parts Evodia rutaecarpa. Crush them separately and pass them through an 80-mesh sieve. Combine them with the remaining mixture and add purified water to make up to 300 parts. Mix them evenly to obtain an aqueous extract mixture. Soak at room temperature for 1 hour and then decoct twice. The first decoction is for 1.5 hours. Filter to obtain the first filtrate and the residue. Add 200 parts purified water to the residue again and decoct for 1 hour. Filter to obtain the second filtrate. Combine the first filtrate and the second filtrate to obtain the decoction filtrate.

[0044] S3: The decoction filtrate was concentrated under reduced pressure at 60℃ and -0.08 MPa to a relative density of 1.10 (measured at 60℃). 500 parts by volume of 95% ethanol were slowly added while stirring to bring the final ethanol volume fraction to 65%. After mixing, the mixture was allowed to stand at 4℃ for 24 hours. The supernatant was collected, filtered, and concentrated again under reduced pressure at 50℃ and -0.09 MPa to a relative density of 1.25 (measured at 60℃) to obtain a refined thick paste.

[0045] S4: Weigh 1 part of borneol, grind it into a fine powder and pass it through a 100-mesh sieve. Add 80 parts of mixed volatile oil and polysorbate to it in sequence, emulsify at 8000 rpm for 5 minutes to obtain a volatile oil emulsion. Add refined thick paste to it while stirring continuously, mix evenly, and obtain a traditional Chinese medicine emulsion thick paste.

[0046] S5: Weigh 0.5 parts of Carbomer 940 and disperse it in 30 parts of purified water. Let it swell at room temperature for 12 hours to obtain a carbomer gel matrix. While stirring, slowly add the traditional Chinese medicine emulsion paste to it and mix evenly. Then, add 1 part of triethanolamine dropwise to adjust the pH of the system to 6.0. Then, add 0.1 parts of EDTA-2Na and continue stirring until completely dissolved to obtain a gel paste. Place it in a vacuum degassing machine for 15 minutes and then homogenize it twice to obtain the traditional Chinese medicine extract.

[0047] The preparation method of the drug-loaded layer is as follows: In a clean environment, PU sponge is molded into a hemispherical drug-loaded matrix with a diameter of 2.5 cm and a height of 1.0 cm. The extract of traditional Chinese medicine is weighed and coated onto the drug-loaded matrix with a coating amount of 1.5 parts. The matrix is ​​placed in a clean workbench and equilibrated for 30 minutes at room temperature and relative humidity of 50% to obtain the drug-loaded layer.

[0048] The preparation method of the drug-loaded pressure-sensitive layer is as follows: place the drug-loaded layer in the center of the mold, uniformly fill the area outside the drug-loaded layer in the mold with silicone gel pressure-sensitive adhesive, and cure in an 80°C oven for 3 minutes to form a drug-loaded pressure-sensitive layer with a length and width of 5.6 cm and a thickness of about 2 mm.

[0049] This embodiment also provides a method for preparing a composite drug-loaded umbilical patch based on a PU film, which specifically includes the following steps:

[0050] Step 1: Apply the drug-loaded pressure-sensitive layer to one side of the PU waterproof protective layer, and heat-press it in an 80℃ oven for 3 minutes to obtain a layered composite substrate;

[0051] Step 2: Take a release film with a pre-set groove of 1.1 cm depth and 2.6 cm diameter, and completely cover the drug-loaded pressure-sensitive layer of the layered composite substrate with the release film. Make sure the groove is accurately engaged with the outside of the hemispherical drug-loaded layer to avoid compressing the drug-loaded layer. Use a rubber roller press to roll the surrounding pressure-sensitive adhesive area to ensure that each layer is tightly bonded to obtain the finished patch. Pack the finished patch into an aluminum foil composite packaging bag, fill it with high-purity nitrogen and heat-seal it to obtain a PU film-based composite drug-loaded umbilical therapy patch.

[0052] Example 2: This example provides a composite drug-loaded umbilical patch based on a PU film, which consists of an anti-adhesive release film, a drug-loaded pressure-sensitive layer, and a PU waterproof protective layer from top to bottom.

[0053] The herbal extract comprises the following raw materials in parts by weight: 15 parts dried ginger, 12 parts stir-fried Atractylodes macrocephala, 10 parts Codonopsis pilosula, 8 parts Evodia rutaecarpa, 8 parts fennel, 6 parts cinnamon, 2 parts borneol, 15 parts polysorbate 80, 1.2 parts carbomer 940, 2 parts triethanolamine, and 0.3 parts EDTA-2Na.

[0054] The preparation method of the traditional Chinese medicine extract includes the following steps:

[0055] S1: Weigh 8 parts of fennel seeds and 6 parts of cinnamon, grind them separately and pass them through an 80-mesh sieve, mix them evenly to obtain mixed volatile oil medicinal materials, put them into a round-bottom flask, add 70 parts of purified water, extract by steam distillation for 6 hours, collect the distillate, let it stand at 4℃ for 12 hours, collect the upper oil phase to obtain mixed volatile oil, collect the lower aqueous phase to obtain aromatic water, combine the aromatic water with the distillation residue in the round-bottom flask to obtain the remaining mixture;

[0056] S2: Weigh 15 parts dried ginger, 12 parts stir-fried Atractylodes macrocephala, 10 parts Codonopsis pilosula, and 8 parts Evodia rutaecarpa. Crush them separately and pass them through an 80-mesh sieve. Combine them with the remaining mixture and add purified water to make up to 500 parts. Mix them evenly to obtain an aqueous extract mixture. Soak it at room temperature for 1 hour and then decoct it twice. The first decoction is for 1.5 hours. Filter it to obtain the first filtrate and the residue. Add 300 parts purified water to the residue again and decoct it for 1 hour. Filter it to obtain the second filtrate. Combine the first filtrate and the second filtrate to obtain the decoction filtrate.

[0057] S3: The decoction filtrate was concentrated under reduced pressure at 60℃ and -0.08 MPa to a relative density of 1.12 (measured at 60℃). 800 parts by volume of 95% ethanol were slowly added while stirring to bring the final ethanol volume fraction to 65%. After mixing, the mixture was allowed to stand at 4℃ for 24 hours. The supernatant was collected, filtered, and concentrated again under reduced pressure at 50℃ and -0.09 MPa to a relative density of 1.28 (measured at 60℃) to obtain a refined thick paste.

[0058] S4: Weigh 2 parts of borneol, grind it into a fine powder and pass it through a 100-mesh sieve. Add 8014 parts of mixed volatile oil and polysorbate to it in sequence, emulsify at 8000 rpm for 5 minutes to obtain a volatile oil emulsion. Add refined thick paste to it while stirring continuously, mix evenly, and obtain a traditional Chinese medicine emulsion thick paste.

[0059] S5: Weigh 1.2 parts of Carbomer 940 and disperse it in 50 parts of purified water. Let it swell at room temperature for 12 hours to obtain a carbomer gel matrix. While stirring, slowly add the traditional Chinese medicine emulsion paste to it and mix evenly. Then, add 2 parts of triethanolamine dropwise to adjust the pH of the system to 6.2. Then, add 0.3 parts of EDTA-2Na and continue stirring until completely dissolved to obtain a gel paste. Place it in a vacuum degassing machine for 15 minutes and then homogenize it twice to obtain the traditional Chinese medicine extract.

[0060] The preparation method of the drug-loaded layer is as follows: In a clean environment, PU sponge is molded into a hemispherical drug-loaded matrix with a diameter of 2.5 cm and a height of 1.0 cm. The extract of traditional Chinese medicine is weighed and coated onto the drug-loaded matrix with a coating amount of 1.5 parts. The matrix is ​​placed in a clean workbench and equilibrated for 30 minutes at room temperature and relative humidity of 50% to obtain the drug-loaded layer.

[0061] The preparation method of the drug-loaded pressure-sensitive layer is as follows: place the drug-loaded layer in the center of the mold, uniformly fill the area outside the drug-loaded layer in the mold with hydrocolloid pressure-sensitive adhesive, and cure in an 80°C oven for 3 minutes to form a drug-loaded pressure-sensitive layer with a length and width of 5.6 cm and a thickness of about 2 mm.

[0062] This embodiment also provides a method for preparing a composite drug-loaded umbilical patch based on a PU film, which specifically includes the following steps:

[0063] Step 1: Apply the drug-loaded pressure-sensitive layer to one side of the PU waterproof protective layer, and heat-press it in an 80℃ oven for 3 minutes to obtain a layered composite substrate;

[0064] Step 2: Take a release film with a pre-set groove of 1.1 cm depth and 2.6 cm diameter, and completely cover the drug-loaded pressure-sensitive layer of the layered composite substrate with the release film. Make sure the groove is accurately engaged with the outside of the hemispherical drug-loaded layer to avoid compressing the drug-loaded layer. Use a rubber roller press to roll the surrounding pressure-sensitive adhesive area to ensure that each layer is tightly bonded to obtain the finished patch. Pack the finished patch into an aluminum foil composite packaging bag, fill it with high-purity nitrogen and heat-seal it to obtain a PU film-based composite drug-loaded umbilical therapy patch.

[0065] Example 3: This example provides a composite drug-loaded umbilical patch based on a PU film, which consists of an anti-adhesive release film, a drug-loaded pressure-sensitive layer, and a PU waterproof protective layer from top to bottom.

[0066] The herbal extract comprises the following raw materials in parts by weight: 20 parts dried ginger, 15 parts stir-fried Atractylodes macrocephala, 12 parts Codonopsis pilosula, 10 parts Evodia rutaecarpa, 10 parts fennel, 8 parts cinnamon, 3 parts borneol, 20 parts polysorbate 80, 2 parts carbomer 940, 3 parts triethanolamine, and 0.5 parts EDTA-2Na.

[0067] The preparation method of the traditional Chinese medicine extract includes the following steps:

[0068] S1: Weigh 10 parts of fennel seeds and 8 parts of cinnamon, grind them separately and pass them through an 80-mesh sieve, mix them evenly to obtain mixed volatile oil medicinal materials, put them into a round-bottom flask, add 90 parts of purified water, extract by steam distillation for 6 hours, collect the distillate, let it stand at 4℃ for 12 hours, collect the upper oil phase to obtain mixed volatile oil, collect the lower aqueous phase to obtain aromatic water, combine the aromatic water with the distillation residue in the round-bottom flask to obtain the remaining mixture;

[0069] S2: Weigh 20 parts of dried ginger, 15 parts of stir-fried Atractylodes macrocephala, 12 parts of Codonopsis pilosula, and 10 parts of Evodia rutaecarpa. Crush them separately and pass them through an 80-mesh sieve. Combine them with the remaining mixture and add purified water to make up to 600 parts. Mix them evenly to obtain an aqueous extract mixture. Soak it at room temperature for 1 hour and then decoct it twice. The first decoction is for 1.5 hours. Filter it to obtain the first filtrate and the residue. Add 400 parts of purified water to the residue again and decoct it for 1 hour. Filter it to obtain the second filtrate. Combine the first filtrate and the second filtrate to obtain the decoction filtrate.

[0070] S3: The decoction filtrate was concentrated under reduced pressure at 60℃ and -0.08 MPa to a relative density of 1.15 (measured at 60℃). 1000 parts by volume of 95% ethanol were slowly added while stirring to bring the final ethanol volume fraction to 65%. After mixing, the mixture was allowed to stand at 4℃ for 24 hours. The supernatant was collected, filtered, and concentrated again under reduced pressure at 50℃ and -0.09 MPa to a relative density of 1.30 (measured at 60℃) to obtain a refined thick paste.

[0071] S4: Weigh 3 parts of borneol, grind it into a fine powder, and pass it through a 100-mesh sieve. Add 8020 parts of mixed volatile oil and polysorbate to the powder in sequence, and emulsify at 8000 rpm for 5 minutes to obtain a volatile oil emulsion. While stirring continuously, add refined thick paste to the powder and mix evenly to obtain a traditional Chinese medicine emulsion thick paste.

[0072] S5: Weigh 2 parts of Carbomer 940 and disperse it in 80 parts of purified water. Let it swell at room temperature for 12 hours to obtain a Carbomer gel matrix. While stirring, slowly add the traditional Chinese medicine emulsion paste to it and mix evenly. Then, add 3 parts of triethanolamine dropwise to adjust the pH of the system to 6.5. Then, add 0.5 parts of EDTA-2Na and continue stirring until completely dissolved to obtain a gel paste. Place it in a vacuum degassing machine for 15 minutes and then homogenize it twice to obtain the traditional Chinese medicine extract.

[0073] The preparation method of the drug-loaded layer is as follows: In a clean environment, PU sponge is molded into a hemispherical drug-loaded matrix with a diameter of 2.5 cm and a height of 1.0 cm. The extract of traditional Chinese medicine is weighed and coated onto the drug-loaded matrix with a coating amount of 1.5 parts. The matrix is ​​placed in a clean workbench and equilibrated for 30 minutes at room temperature and relative humidity of 50% to obtain the drug-loaded layer.

[0074] The preparation method of the drug-loaded pressure-sensitive layer is as follows: place the drug-loaded layer in the center of the mold, uniformly fill the area outside the drug-loaded layer in the mold with silicone gel pressure-sensitive adhesive, and cure in an 80°C oven for 3 minutes to form a drug-loaded pressure-sensitive layer with a length and width of 5.6 cm and a thickness of about 2 mm.

[0075] This embodiment also provides a method for preparing a composite drug-loaded umbilical patch based on a PU film, which specifically includes the following steps:

[0076] Step 1: Apply the drug-loaded pressure-sensitive layer to one side of the PU waterproof protective layer, and heat-press it in an 80℃ oven for 3 minutes to obtain a layered composite substrate;

[0077] Step 2: Take a release film with a pre-set groove of 1.1 cm depth and 2.6 cm diameter, and completely cover the drug-loaded pressure-sensitive layer of the layered composite substrate with the release film. Make sure the groove is accurately engaged with the outside of the hemispherical drug-loaded layer to avoid compressing the drug-loaded layer. Use a rubber roller press to roll the surrounding pressure-sensitive adhesive area to ensure that each layer is tightly bonded to obtain the finished patch. Pack the finished patch into an aluminum foil composite packaging bag, fill it with high-purity nitrogen and heat-seal it to obtain a PU film-based composite drug-loaded umbilical therapy patch.

[0078] The difference between Comparative Example 1 and Example 1 is that no Chinese herbal extract was used. Instead, the Chinese herbal medicine was ground and sieved to obtain raw powder according to the formula of Example 1, which was then mixed into a paste and coated onto a PU sponge. The rest of the process was the same as in Example 1.

[0079] The difference between Comparative Example 2 and Example 1 is that no PU waterproof protective layer was used. Instead, the Chinese herbal extract was coated on non-woven fabric. The rest of the parts are the same as in Example 1.

[0080] The difference between Comparative Example 3 and Example 1 is that the medical-grade PU film is replaced with a PE (polyethylene) film of the same thickness, while the rest is the same as Example 1.

[0081] In vitro transdermal absorption test

[0082] The composite drug-loaded umbilical patches prepared in Examples 1-3 and Comparative Examples 1-3 were punched using a ring mold with an inner diameter of 2.5 cm to obtain a drug-containing area of ​​4.91 cm². 2 The sample was circular. The effective diffusion area was simultaneously adjusted to 4.91 cm². 2 A modified Franz vertical diffusion cell was used, with fresh detached pigskin as the permeability barrier. Circular samples were attached to the surface of the pigskin and placed in the supply chamber of the Franz diffusion cell. The receiving chamber was injected with 35 mL of physiological saline (containing 0.01% NaN3), and the mixture was stirred at 37℃ and 300 rpm. Samples were taken after 24 hours, and the concentration of 6-gingerol in the receiving solution was determined by HPLC. The results are shown below. Figure 2 Cumulative throughput Q 24 =C 24 ×V r / A, where C 24 V represents the drug concentration in the receiving solution after 24 hours. r A represents the volume of liquid to be received, and A represents the effective diffusion area.

[0083] Rabbit skin irritation test

[0084] Six healthy adult New Zealand rabbits (weighing 2.0-2.5 kg) were selected. Before the experiment, the fur was shaved symmetrically on both sides of the spine on the back (area 10 cm × 15 cm) to ensure that the skin was intact and undamaged. The back of each rabbit was divided into 6 independent test areas, corresponding to the composite drug-loaded umbilical patches prepared in Examples 1-3 and Comparative Examples 1-3, respectively, and applied continuously for 24 hours. At four time points after the patches were removed, the skin reaction of each test area was observed and recorded, and the two indicators of erythema and edema were evaluated. The scoring was based on the standards of the "Cosmetic Safety Technical Specifications" (2015 edition): erythema score was 0-4 points (0=none, 1=mild, 2=obvious, 3=moderate to severe, 4=purplish-red with eschar), and edema score was 0-4 points (0=none, 1=mild, 2=obvious, 3=raised about 1 mm, 4=raised more than 1 mm). The total score for each animal at each time point is the sum of the erythema score and the edema score. The average score of each group of animals at each time point is used for subsequent analysis. The Stimulation Index (PII) is calculated as (24-hour total score + 48-hour total score) / (2 × number of animals). The stimulation intensity is determined based on the PII value: 0-0.49 indicates no stimulation, 0.5-2.99 indicates mild stimulation, 3.0-5.99 indicates moderate stimulation, and 6.0-8.0 indicates strong stimulation.

[0085] Table 1 Results of skin irritation test on rabbits

[0086]

[0087] Rat pharmacodynamic testing and comprehensive evaluation of topical performance

[0088] To evaluate the pharmacodynamics and topical properties of the compound drug-loaded umbilical patch, a spleen-stomach deficiency-cold type abdominal pain model was established. The following experimental groups were set up: a blank control group (healthy rats), a model control group (model rats + blank PU film patch), and treatment groups (model rats + corresponding compound drug-loaded umbilical patches) of Example 1 and Comparative Examples 1-3, with 8 rats in each group. The patch was applied to the shaved area of ​​the rat's abdomen (simulating the Shenque acupoint), and changed daily for 7 consecutive days. Two hours after the last administration, serum was collected from each group of rats, and the levels of motilin (MTL), gastrin (GAS), and vasoactive intestinal peptide (VIP) were detected using enzyme-linked immunosorbent assay (ELISA). The results are as follows: Figure 3 As shown.

[0089] During the 7-day experimental period, the fixation stability of the composite drug-loaded umbilical patch (the proportion of displacement / fallout within 24 hours), the degree of soiling of hair and bedding (0-3 points), and the animals' discomfort behaviors (average number of scratching and licking times per hour) were observed and recorded daily. The results are shown in Table 2.

[0090] Table 2 Observation Results of External Performance Indicators

[0091]

[0092] Results Analysis

[0093] Figure 2 The results showed that Examples 1-3 exhibited superior transdermal performance, with a cumulative 6-gingerol permeation rate exceeding 13 μg / cm³ over 24 hours. 2 All values ​​were significantly higher than those of comparative examples 1-3. Among them, comparative example 3, which used a PE membrane, suffered from poor air permeability leading to a local microenvironment imbalance, and its cumulative 6-gingerol permeation was 8.2 μg / cm³. 2 and 9.5 μg / cm 2 The results were significantly lower than those of Examples 1-3, which used PU film.

[0094] Table 1 shows that the PII values ​​of Examples 1-3 were 0.3-0.7, all within the non-irritating range; while the PII value of Comparative Example 1, which used a paste-like traditional Chinese medicine powder, reached 1.8-2.8, indicating mild irritation. Meanwhile, the skin irritation of Comparative Example 2 (PII 1.2-1.5) without a PU waterproof protective layer and Comparative Example 3 (PII 1.3-2.3) using a PE film were significantly higher than those of Examples 1-3.

[0095] Figure 3 The results showed that, compared with the model control group, Example 1 increased the serum motilin level in rats with spleen and stomach deficiency and cold from 215.8 pg / mL to 325.6 pg / mL, increased the gastrin level from 45.2 pg / mL to 78.9 pg / mL, and decreased the vasoactive intestinal peptide level from 98.7 pg / mL to 68.4 pg / mL. All three indicators were close to the levels of the blank control group (352.4 pg / mL, 85.6 pg / mL, and 62.3 pg / mL).

[0096] Table 2 shows that, in the observation of external application performance, Example 1 did not shift or fall off within 24 hours, while Comparative Example 2, due to the lack of a fixing layer, all shifted or fell off; during the 7-day experimental period, the average number of scratches (1.2 times / hour) and the average number of licks (0.8 times / hour) of Example 1 were significantly lower than those of Comparative Example 1 (2.0 times / hour and 2.5 times / hour); the hair staining score (0 points) and the padding staining score (0 points) of Example 1 were significantly better than those of Comparative Example 2 (2.5 points and 2.0 points).

[0097] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

[0098] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A composite drug-loaded umbilical patch based on a PU film, characterized in that, The composite drug-loaded umbilical patch consists of, from top to bottom, an anti-adhesive release film, a drug-loaded pressure-sensitive layer, and a PU waterproof protective layer. The drug-loaded pressure-sensitive layer includes a medical pressure-sensitive adhesive and a drug-loaded layer; The drug-loaded layer is prepared by coating a carrier matrix with a traditional Chinese medicine extract; The drug-carrying layer is a hemispherical structure that conforms to the shape of the navel; The herbal extract comprises the following raw materials in parts by weight: dried ginger, stir-fried Atractylodes macrocephala, Codonopsis pilosula, Evodia rutaecarpa, fennel, cinnamon, borneol, polysorbate, carbomer, triethanolamine, and EDTA-2Na. The preparation method of the herbal extract is as follows: S1: Crush, sieve, distill and separate fennel and cinnamon to obtain mixed volatile oil and aromatic water. Combine the aromatic water with the distillation residue to obtain the remaining mixture. S2: Weigh out dried ginger, stir-fried Atractylodes macrocephala, Codonopsis pilosula and Evodia rutaecarpa, crush and sieve them, combine them with the remaining mixture, soak, decoct and filter to obtain decoction filtrate; S3: After concentrating the decoction filtrate under reduced pressure, add 95% ethanol (by volume), let stand, filter, and concentrate again under reduced pressure to obtain a refined thick paste. S4: Grind borneol into a fine powder, mix it with mixed volatile oil and polysorbate 80, emulsify it, and add refined thick paste to obtain traditional Chinese medicine emulsified thick paste; S5: Carbomer 940 was dispersed in purified water, and a traditional Chinese medicine emulsion was added to it. Triethanolamine and EDTA-2Na were added dropwise. After degassing and homogenization, the traditional Chinese medicine extract was obtained.

2. The composite drug-loaded umbilical patch based on a PU film according to claim 1, characterized in that, The weight parts of the following ingredients are respectively 15-25, 10-20, 10-15, 8-12, 5-10, 5-10, 3-8, 1-3, 8-20, 0.5-2, 1-3 and 0.1-0.

5.

3. The composite drug-loaded umbilical patch based on a PU film according to claim 1, characterized in that, The preparation method of the drug-loaded pressure-sensitive layer is as follows: a hemispherical drug-loaded layer is placed in a mold, and medical pressure-sensitive adhesive is filled around it to form a drug-loaded pressure-sensitive layer with a drug-loaded layer in the center and medical pressure-sensitive adhesive on the periphery.

4. The composite drug-loaded umbilical patch based on a PU film according to claim 1, characterized in that, The carrier matrix is ​​a PU sponge molded into a hemispherical shape.

5. A composite drug-loaded umbilical patch based on a PU film according to claim 4, characterized in that, The anti-stick release film is made of glassine paper treated with silicone oil and has a groove structure adapted to the shape of the drug-loaded layer.

6. The composite drug-loaded umbilical patch based on a PU film according to claim 3, characterized in that, The medical pressure-sensitive adhesive is selected from any one of silicone gel pressure-sensitive adhesive, hydrocolloid pressure-sensitive adhesive, and acrylic pressure-sensitive adhesive.

7. A method for preparing a composite drug-loaded umbilical patch based on a PU film according to any one of claims 1-6, characterized in that, The specific preparation method is as follows: Step 1: Place the drug-loaded pressure-sensitive layer on the PU waterproof protective layer and bond it by hot pressing to obtain a layered composite substrate; Step 2: Take the anti-adhesive release film and cover it on the layered composite substrate, then encapsulate it to obtain a PU film-based composite drug-loaded umbilical therapy patch.

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