External anti-inflammation and fire-removing patch and preparation method thereof

Abstract

The invention relates to the technical field of anti-inflammatory and fire-removing patches, in particular to an external anti-inflammatory and fire-removing patch, which is prepared from the following components in parts by weight: 15 parts of honeysuckle, 10 parts of rhizoma anemarrhenae, 15 parts of gypsum, 15 parts of fructus gardeniae, 8 parts of borneol, 8 parts of menthol, 12 parts of radix paeoniae rubra, 15 parts of radix scutellariae, 10 parts of mirabilitum praeparatum, 12 parts of herba violae, 10 parts of radix scrophulariae, 8 parts of fructus forsythiae and 6 parts of liquorice. The preparation method of the external anti-inflammation and fire-removing patch comprises the following steps: step 1, directionally extracting modular active components, and respectively extracting components of a module A, a module B and a module C; step 2, constructing a functional matrix and designing a transdermal system, and constructing a temperature-sensitive hydrogel matrix and a transdermal enhancement system. According to the modular extraction technology, supercritical CO2, enzymolysis and ultrasonic processes are optimized in a modular mode, loss of thermosensitive components in traditional water extraction and alcohol precipitation is avoided, for example, the retention rate of borneol is increased from 75% to 95%.

Description

Technical Field

[0001] The invention relates to the technical field of anti-inflammatory and heat-removing patches, in particular to an external anti-inflammatory and heat-removing patch and a preparation method thereof. Background Art

[0002] Anti-inflammatory and anti-fire patches are external-use patches that usually contain some traditional Chinese medicine ingredients or chemical drug ingredients that have anti-inflammatory, heat-clearing, and detoxifying effects.

[0003] Its main working principle is that the drug ingredients in the patch penetrate through the skin and act on local tissues, playing a role in reducing inflammation, relieving pain, eliminating swelling, etc. It may have a certain auxiliary therapeutic effect on some local redness, swelling, heat and pain caused by internal heat, such as carbuncle, oral ulcer, sore throat, etc.

[0004] Traditional patches have low transdermal penetration rates (e.g., the transdermal penetration rate of azone permeation enhancer is only 12%), and the high-temperature process causes the volatilization loss of heat-sensitive ingredients such as borneol and menthol (retention rate ≤ 75%).

[0005] Therefore, a kind of external anti-inflammatory and fire-clearing patch and preparation method thereof are proposed. Summary of the Invention

[0006] The purpose of the present invention is to provide an external anti-inflammatory and heat-removing patch and a preparation method thereof, so as to solve the problems raised in the above background technology.

[0007] To achieve the above object, the present invention provides the following technical solution: an external anti-inflammatory and heat-removing patch comprising the following parts by weight:

[0008] 15 parts of Flos Honeysuckle, 10 parts of Rhizoma Anemarrhenae, 15 parts of Gypsum, 15 parts of Fructus Gardeniae, 8 parts of Borneolum Syntheticum, 8 parts of Mentholum, 12 parts of Radix Paeoniae Rubra, 15 parts of Radix Scutellariae, 10 parts of Citrus aurantium, 12 parts of Herba Violae Yensis, 10 parts of Scrophulariae, 8 parts of Fructus Forsythiae, 6 parts of Radix Glycyrrhizae.

[0009] A method for preparing an external anti-inflammatory and heat-removing patch comprises the following steps:

[0010] Step 1: Modular active ingredient directional extraction, extracting components from module A, module B, and module C respectively;

[0011] Step 2: Functional matrix construction and transdermal system design, constructing a thermosensitive hydrogel matrix and transdermal enhancement system;

[0012] Step three: gradient molding process, which is made by 3D printing the drug-carrying layer, mineralized protective layer and self-adhesive breathable backing;

[0013] Step 4: Quality verification and performance testing, testing the transdermal efficiency, sustained release performance and stability respectively.

[0014] Preferably, in the step 1, module A in the modular active ingredient directional extraction comprises 15 parts of honeysuckle, 15 parts of scutellaria baicalensis and 15 parts of gypsum, and supercritical CO2 two-gradient extraction is adopted;

[0015] The first stage: extract chlorogenic acid and baicalin from honeysuckle at a temperature of 35°C and a pressure of 25 MPa, retaining heat-sensitive components;

[0016] The second stage: extracting Ca from gypsum at a temperature of 50°C and a pressure of 30 MPa 2+ and sulfate ions, increasing the dissolution rate of mineral ions;

[0017] Module B includes 10 parts of Anemarrhena Rhizoma, 11 parts of Red Peony Root, and 15 parts of Gardenia Fructus. It is pretreated with enzymatic hydrolysis using cellulase at pH 4.5 and 50°C for 2 hours to destroy the plant cell wall structure. Then, ultrasonic-assisted extraction is used to extract Anemarrhena Rhizoma saponins, Red Peony Root, and Gardenia Fructus saponins at 40 kHz and 800 W.

[0018] Module C includes 8 parts of borneol, 8 parts of menthol, and 10 parts of watermelon frost, and is encapsulated in nanoliposomes. Borneol and menthol are mixed in a ratio of 1:1, soybean lecithin and cholesterol are mixed in a ratio of 4:1, and liposomes with a particle size of ≤100nm are prepared by a thin film dispersion method.

[0019] Preferably, in the step 2, the thermosensitive hydrogel matrix in the functional matrix construction and transdermal system design includes 3% sodium alginate, 15% poloxamer 407, and 5% sodium carboxymethyl cellulose, which forms a porous network structure at 37°C with a porosity of >85% and a water vapor permeability of 2200 g / m 2 After 24 hours, gypsum nanocluster ions were loaded into the micropores of sodium alginate, and geniposide and anemarrhena saponin were encapsulated by poloxamer micelles.

[0020] Preferably, the skin penetration enhancement system:

[0021] Liposomes are co-loaded with mesoporous silica with a pore size of 3 nm: the liposomes release borneol / menthol through a phase change triggered by body temperature, and the mesoporous structure prolongs the release time of watermelon frost ions, with a 24-hour sustained release rate of >80%.

[0022] Preferably, in step three, the drug-loaded layer is 3D printed in a gradient molding process, wherein the microneedle mold parameters are: needle height 500 μm, needle tip diameter 50 μm, and drug-loaded density gradient design;

[0023] Gradient drug loading: outer layer, needle tip: high concentration gypsum ion cluster + honeysuckle extract; inner layer, needle body: timosaponin-gardena jasminoides sustained-release micelles;

[0024] Printing parameters: temperature 25°C, pressure 0.2 MPa, layer thickness 0.1 mm, accuracy error <5%.

[0025] Preferably, in the step 3, the mineralized protective layer is prepared in the gradient molding process, using watermelon frost nanopowder, wet ball milling to D50 = 200nm, and hypromellose, HPMC and watermelon frost nanopowder, mixed and coated in a ratio of 3:7 to form a mineralized film with a thickness of 50μm, which dissolves and releases K after encountering sweat. + 、NO3 - ion.

[0026] Preferably, in step 3, a self-adhesive breathable backing is prepared in a gradient forming process, and a PLGA / chitosan nanofiber membrane is formed in a ratio of 7:3, with the following parameters: voltage 20 kV, spinning speed 1.5 mL / h, pore size 1-5 μm, and moisture permeability ≥ 2000 g / m 2 ·24h.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] Modular extraction technology: Optimize supercritical CO2, enzymatic hydrolysis, and ultrasonic processes in modules to avoid the loss of heat-sensitive components in traditional water extraction and alcohol precipitation (e.g., the borneol retention rate is increased from 75% to 95%).

[0029] Structural bionic design: The 3D-printed microneedle gradient drug-carrying layer simulates the skin penetration path, shortening the onset time to 15 minutes (traditional patches take 1 hour).

[0030] Dual-channel transdermal system: liposomes (triggered by body temperature) and mesoporous silica (pH response) work together to achieve a transdermal efficiency 1.8 times that of traditional azone and is non-irritating. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0032] Figure 1 The present invention is a flow chart of a method for preparing an external anti-inflammatory and heat-removing patch. DETAILED DESCRIPTION

[0033] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0034] See also Figure 1 , the present invention provides a technical solution:

[0035] An external anti-inflammatory and heat-removing patch comprising the following parts by weight:

[0036] 15 parts of Flos Honeysuckle, 10 parts of Rhizoma Anemarrhenae, 15 parts of Gypsum, 15 parts of Fructus Gardeniae, 8 parts of Borneolum Syntheticum, 8 parts of Mentholum, 12 parts of Radix Paeoniae Rubra, 15 parts of Radix Scutellariae, 10 parts of Citrus aurantium, 12 parts of Herba Violae Yensis, 10 parts of Scrophulariae, 8 parts of Fructus Forsythiae, 6 parts of Radix Glycyrrhizae.

[0037] A method for preparing an external anti-inflammatory and heat-removing patch comprises the following steps:

[0038] Step 1: Modular active ingredient directional extraction, extracting components from module A, module B, and module C respectively;

[0039] Step 2: Functional matrix construction and transdermal system design, constructing a thermosensitive hydrogel matrix and transdermal enhancement system;

[0040] Step three: gradient molding process, which is made by 3D printing the drug-carrying layer, mineralized protective layer and self-adhesive breathable backing;

[0041] Step 4: Quality verification and performance testing, testing the transdermal efficiency, sustained release performance and stability respectively.

[0042] Specifically, in step 1, module A in the modular active ingredient directional extraction includes 15 parts of honeysuckle, 15 parts of scutellaria baicalensis and 15 parts of gypsum, and supercritical CO2 two-gradient extraction is used;

[0043] The first stage: extract chlorogenic acid and baicalin from honeysuckle at a temperature of 35°C and a pressure of 25 MPa, retaining heat-sensitive components;

[0044] The second stage: extracting Ca from gypsum at a temperature of 50°C and a pressure of 30 MPa 2+ and sulfate ions, increasing the dissolution rate of mineral ions;

[0045] Module B includes 10 parts of Anemarrhena Rhizoma, 11 parts of Red Peony Root, and 15 parts of Gardenia Fructus. It is pretreated with enzymatic hydrolysis using cellulase at pH 4.5 and 50°C for 2 hours to destroy the plant cell wall structure. Then, ultrasonic-assisted extraction is used to extract Anemarrhena Rhizoma saponins, Red Peony Root, and Gardenia Fructus saponins at 40 kHz and 800 W.

[0046] Module C includes 8 parts of borneol, 8 parts of menthol, and 10 parts of watermelon frost, and is encapsulated in nanoliposomes. Borneol and menthol are mixed in a ratio of 1:1, soybean lecithin and cholesterol are mixed in a ratio of 4:1, and liposomes with a particle size of ≤100nm are prepared by a thin film dispersion method.

[0047] Specifically, in the second step, the thermosensitive hydrogel matrix in the functional matrix construction and transdermal system design includes 3% sodium alginate, 15% poloxamer 407, and 5% sodium carboxymethyl cellulose, which forms a porous network structure at 37°C with a porosity of >85% and a moisture permeability of 2200g / m 2 After 24 hours, gypsum nanocluster ions were loaded into the micropores of sodium alginate, and geniposide and anemarrhena saponin were encapsulated by poloxamer micelles.

[0048] Specifically, the skin permeation enhancement system:

[0049] Liposomes are co-loaded with mesoporous silica with a pore size of 3 nm: the liposomes release borneol / menthol through a phase change triggered by body temperature, and the mesoporous structure prolongs the release time of watermelon frost ions, with a 24-hour sustained release rate of >80%.

[0050] Specifically, in step three, the drug-loaded layer is 3D printed in a gradient molding process, wherein the microneedle mold parameters are: needle height 500 μm, needle tip diameter 50 μm, and drug-loaded density gradient design;

[0051] Gradient drug loading: outer layer, needle tip: high concentration gypsum ion cluster + honeysuckle extract; inner layer, needle body: timosaponin-gardena jasminoides sustained-release micelles;

[0052] Printing parameters: temperature 25°C, pressure 0.2 MPa, layer thickness 0.1 mm, accuracy error <5%.

[0053] Specifically, in step 3, the mineralized protective layer is prepared in the gradient molding process, using watermelon frost nanopowder, wet ball milling to D50 = 200nm, and hypromellose, HPMC and watermelon frost nanopowder, mixed and coated in a ratio of 3:7 to form a mineralized film with a thickness of 50μm, which dissolves and releases K after encountering sweat. + 、NO3 - ion.

[0054] Specifically, in step 3, a self-adhesive breathable backing is prepared in a gradient molding process, and a PLGA / chitosan nanofiber membrane is formed in a ratio of 7:3. The parameters are voltage 20kV, spinning speed 1.5mL / h, pore size 1-5μm, and moisture permeability ≥2000g / m 2 ·24h.

[0055] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An external anti-inflammatory and heat-removing patch, characterized in that: Comprises the following weight parts: 15 parts of Flos Honeysuckle, 10 parts of Rhizoma Anemarrhenae, 15 parts of Gypsum, 15 parts of Fructus Gardeniae, 8 parts of Borneolum Syntheticum, 8 parts of Mentholum, 12 parts of Radix Paeoniae Rubra, 15 parts of Radix Scutellariae, 10 parts of Citrus aurantium, 12 parts of Herba Violae Yensis, 10 parts of Scrophulariae, 8 parts of Fructus Forsythiae, 6 parts of Radix Glycyrrhizae.

2. A method for preparing an external anti-inflammatory and anti-inflammatory patch, characterized in that: The steps include: Step 1: Modular active ingredient directional extraction, extracting components from module A, module B, and module C respectively; Step 2: Functional matrix construction and transdermal system design, constructing a thermosensitive hydrogel matrix and transdermal enhancement system; Step three: gradient molding process, which is made by 3D printing the drug-carrying layer, mineralized protective layer and self-adhesive breathable backing; Step 4: Quality verification and performance testing, testing the transdermal efficiency, sustained release performance and stability respectively.

3. The external anti-inflammatory and heat-clearing patch according to claim 2, wherein: In the step 1, module A in the modular active ingredient directional extraction includes 15 parts of honeysuckle, 15 parts of scutellaria and 15 parts of gypsum, and supercritical CO2 two-gradient extraction is used; The first stage: extract chlorogenic acid and baicalin from honeysuckle at a temperature of 35°C and a pressure of 25 MPa, retaining heat-sensitive components; The second stage: extracting Ca from gypsum at a temperature of 50°C and a pressure of 30 MPa 2+ and sulfate ions, increasing the dissolution rate of mineral ions; Module B includes 10 parts of Anemarrhena Rhizoma, 11 parts of Red Peony Root, and 15 parts of Gardenia Fructus. It is pretreated with enzymatic hydrolysis using cellulase at pH 4.5 and 50°C for 2 hours to destroy the plant cell wall structure. Then, ultrasonic-assisted extraction is used to extract Anemarrhena Rhizoma saponins, Red Peony Root, and Gardenia Fructus saponins at 40 kHz and 800 W. Module C includes 8 parts of borneol, 8 parts of menthol, and 10 parts of watermelon frost, and is encapsulated in nanoliposomes. Borneol and menthol are mixed in a ratio of 1:1, soybean lecithin and cholesterol are mixed in a ratio of 4:1, and liposomes with a particle size of ≤100nm are prepared by a thin film dispersion method.

4. The method for preparing the external anti-inflammatory and anti-inflammatory patch according to claim 3, wherein: In the second step, the thermosensitive hydrogel matrix in the functional matrix construction and transdermal system design includes 3% sodium alginate, 15% poloxamer 407, and 5% sodium carboxymethyl cellulose, which forms a porous network structure at 37°C with a porosity of >85% and a water vapor permeability of 2200g / m 2 After 24 hours, gypsum nanocluster ions were loaded into the micropores of sodium alginate, and geniposide and anemarrhena saponin were encapsulated by poloxamer micelles.

5. The method for preparing the external anti-inflammatory and heat-removing patch according to claim 4, wherein: The transdermal enhancement system: Liposomes are co-loaded with mesoporous silica with a pore size of 3 nm: the liposomes release borneol / menthol through a phase change triggered by body temperature, and the mesoporous structure prolongs the release time of watermelon frost ions, with a 24-hour sustained release rate of >80%.

6. The method for preparing the external anti-inflammatory and heat-removing patch according to claim 5, wherein: In the step three, the drug-loaded layer is 3D printed in a gradient molding process, wherein the microneedle mold parameters are: needle height 500 μm, needle tip diameter 50 μm, and drug-loaded density gradient design; Gradient drug loading: outer layer, needle tip: high concentration gypsum ion cluster + honeysuckle extract; inner layer, needle body: timosaponin-gardena jasminoides sustained-release micelles; Printing parameters: temperature 25°C, pressure 0.2 MPa, layer thickness 0.1 mm, accuracy error <5%.

7. The method for preparing the external anti-inflammatory and heat-removing patch according to claim 6, wherein: In the step 3, the mineralized protective layer is prepared in the gradient molding process. Watermelon frost nanopowder is wet-ball-milled to a D50 of 200 nm, and hydroxypropyl methylcellulose, HPMC and watermelon frost nanopowder are mixed and coated in a ratio of 3:7 to form a mineralized film with a thickness of 50 μm. When it encounters sweat, it dissolves and releases K + 、NO3 - ion.

8. The method for preparing the external anti-inflammatory and heat-removing patch according to claim 7, wherein: In the step 3, a self-adhesive breathable backing is prepared in a gradient forming process, and a PLGA / chitosan ratio of 7:3 is used to form a nanofiber membrane. The parameters are voltage 20kV, spinning speed 1.5mL / h, pore size 1-5μm, and moisture permeability ≥2000g / m 2 ·24h.

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