An antibacterial drug-loaded patch for skin repair and its preparation.

Abstract

The present invention relates to an antibacterial drug-loaded patch for repairing skin and its preparation, belonging to the technical field of medical or cosmetic preparations. The antibacterial drug-loaded patch of the present invention is composed of costus root volatile oil, capillaris extract, hyaluronic acid, glycerol, deionized water, EGCG-pectin complex, backing material, and protective layer. The present invention uses capillaris extract and costus root volatile oil as main drugs to prepare the drug-loaded patch, and verifies the antibacterial ability and skin permeability of the drug-loaded patch, providing a drug-loaded patch with simple ingredients, high safety, and good antibacterial effect.

Description

Technical Field

[0001] The invention belongs to the technical field of medical or cosmetic preparations, and in particular relates to an antibacterial drug-carrying patch for repairing skin and a preparation method thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] As the largest organ in the human body, the skin plays an important protective role. However, factors such as the external environment, trauma or infection often lead to skin damage and bacterial infection. Traditional skin treatment methods mostly rely on topical ointments or sprays, which have certain limitations in drug release, penetration and therapeutic effect.

[0004] In recent years, with the development of biomaterials science and drug delivery systems, drug-loaded patches have gradually attracted attention. Such patches are usually made of biocompatible materials and can effectively release drugs to damaged skin areas to enhance the therapeutic effect. In addition, drug-loaded patches can also provide a physical barrier to prevent secondary infection while maintaining a suitable humidity environment to promote wound healing.

[0005] The Chinese patent with publication number CN114939136A discloses a skin gel patch loaded with a nano-suspension of traditional Chinese medicine, including a nano-suspension and a gel matrix, wherein the nano-suspension includes the following components: Tremella fuciformis extract, wild chrysanthemum extract, scutellaria baicalensis extract, sophora flavescens root extract, microphylla algae extract, orange peel, willow bark, golden flower grass, cassia seed, salvia miltiorrhiza and Poria cocos, and the ratio of the nano-suspension to the gel matrix is ​​1 to 10: 100. However, the components of the traditional Chinese medicine and the traditional Chinese medicine extract of the drug-carrying patch are relatively complex, and its safety is difficult to control and ensure.

[0006] The Chinese patent with publication number CN111388409A discloses a skin antipruritic and antibacterial patch, the preparation steps of which are: (1) grafting modification of galactomannan; (2) thickening treatment of sodium alginate; (3) preparation of auxiliary materials; (4) preparation of hydrogel materials. This technical solution has a high production cost and is difficult to industrialize.

[0007] Antibacterial drug-loaded patches for skin damage have shown broad prospects in clinical applications and provide a novel and effective solution for skin repair. The present application provides a drug-loaded patch with simple ingredients, high safety and good antibacterial effect. Summary of the invention

[0008] The present invention overcomes the shortcomings of the prior art and provides an antibacterial drug-loaded patch for repairing skin with simple ingredients, high safety and good antibacterial effect, which is composed of a drug-containing glue and a film cloth; the drug-containing glue is calculated by mass fraction as follows: 2.5% to 6.5% of costusroot volatile oil (CAS: 8023-88-9, molecular formula: C 10 H 10 O4, molecular weight: 194.184), 0.8%~2.8% Artemisia capillaris extract, 1.0%~3.0% hyaluronic acid, 10%~20% glycerol, appropriate amount of deionized water, 15%~25% EGCG-pectin (CAS No. 9000-69-5, molecular formula: C5H 10 O5) composite; the membrane cloth consists of a backing material and a protective layer.

[0009] Furthermore, the Artemisia capillaris extract is extracted according to the preparation method under the item of Artemisia capillaris extract in Part 4 of the 2020 edition of the "Chinese Pharmacopoeia", specifically: take Artemisia capillaris, use 90% ethanol as a solvent, soak for 24 hours and then percolate, collect the percolate, filter, and decompress the filtrate to a clear paste with a relative density of 1.10~1.15 (60~65°C), add 6~7 times the amount of water, refrigerate, let stand, filter, heat the filtrate at 120°C for 1 hour, refrigerate, let stand, add 0.2% activated carbon, filter, and decompress the filtrate to a clear paste with a relative density of 1.15~1.20 (60~65°C), and vacuum dry below 80°C.

[0010] Among them, according to the provisions of the "Chinese Pharmacopoeia", the chlorogenic acid content in the Artemisia Capillaris extract is not less than 1.0%, and the p-hydroxyacetophenone content is not less than 0.10%.

[0011] Furthermore, the preparation method of the EGCG-pectin complex is as follows: pectin is added to a 0.01 mol / l buffer solution, placed in a 50-55°C water bath and stirred for 30-40 min to prepare a 20 mg / ml pectin solution; a 35 mmol / l EGCG solution is added to the pectin solution while stirring to obtain the EGCG-pectin complex.

[0012] Wherein, the buffer solution is a phosphate buffer solution, a citrate buffer solution or a carbonate buffer solution.

[0013] The preparation method of the above-mentioned antibacterial drug-loaded patch for repairing skin comprises the following steps:

[0014] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, and freeze-thaw repeatedly 2 to 4 times at a temperature of -10°C ± 5°C for 2 to 5 hours. After thawing to room temperature, add costus root volatile oil and EGCG-pectin complex, mix well, add deionized water to the full amount, mix well, and sonicate for 5 to 15 minutes to obtain a drug-containing gel solution;

[0015] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0016] Compared with the prior art, the technical effects of the present invention are:

[0017] (1) The present invention uses Artemisia capillaris extract and costusroot volatile oil as main drugs to prepare drug-loaded patches, and verifies the antibacterial ability of the drug-loaded patches.

[0018] (2) The volatile oil of costusroot plays a dual role in the present invention: one is synergistic antibacterial effect, and the other is to promote drug penetration so that it can exert better therapeutic effects.

[0019] (3) The present invention improves the pressure-sensitive adhesive and uses EGCG-modified pectin as one of the drug-carrying materials, which effectively promotes the skin permeability of drugs and increases the local drug concentration in the skin, which is beneficial to promoting wound healing and playing an antibacterial role. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 : Skin reaction scores of New Zealand rats in each group after drug administration.

[0021] Figure 2 : The antibacterial ability of the antibacterial drug-loaded patches of Examples 1 to 5 and the antibacterial drug-loaded patches of Comparative Examples 1 to 4. DETAILED DESCRIPTION

[0022] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0023] EGCG-pectin complex A: Pectin (Merck, P9135) was added to 0.01 mol / l phosphate buffer solution, placed in a 53°C water bath and stirred for 30-40 min to prepare a 20 mg / ml pectin solution; 35 mmol / l EGCG solution was added to the pectin solution while stirring to obtain an EGCG-pectin complex.

[0024] EGCG-pectin complex B: Pectin (Merck, P9135) was added to 0.01 mol / l citrate buffer solution, placed in a 50°C water bath and stirred for 30-40 min to prepare a 20 mg / ml pectin solution; 35 mmol / l EGCG solution was added to the pectin solution while stirring to obtain an EGCG-pectin complex.

[0025] EGCG-pectin complex C: Pectin (Merck, P9135) was added to a 0.01 mol / l carbonate solution, placed in a 55°C water bath and stirred for 30-40 min to prepare a 20 mg / ml pectin solution; 35 mmol / l EGCG solution was added to the pectin solution while stirring to obtain an EGCG-pectin complex.

[0026] Table 1 Thermodynamic parameters of the interaction between EGCG and pectin

[0027]

[0028] The thermodynamic parameters of the interaction between the two substances of EGCG-pectin complex A, EGCG-pectin complex B and EGCG-pectin complex C were determined by isothermal titration calorimeter ITC. For the judgment of the type of interaction force, the study showed that: when ΔH>0, ΔS>0, the main interaction force is hydrophobic interaction force; when ΔH<0, ΔS>0, electrostatic interaction force plays a major role; when ΔH<0, ΔS<0, hydrogen bond and van der Leyen interaction force play a major role.

[0029] The ΔG of pectin and EGCG were both negative, indicating that the interaction between pectin and EGCG could be spontaneous.

[0030] Example 1 Antibacterial drug-loaded patch

[0031] formula:

[0032]

[0033] Preparation method:

[0034] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, freeze and thaw repeatedly for 3 times at -10°C for 4 h, add costusroot volatile oil and EGCG-pectin complex after thawing to room temperature, mix well, add deionized water to the full amount, mix well, and sonicate for 10 min to obtain the drug-containing gel solution;

[0035] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0036] Example 2 Antibacterial drug-loaded patch

[0037] formula:

[0038]

[0039] Preparation method:

[0040] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, freeze and thaw repeatedly for 3 times at -10°C for 4 h, add costusroot volatile oil and EGCG-pectin complex after thawing to room temperature, mix well, add deionized water to the full amount, mix well, and sonicate for 10 min to obtain the drug-containing gel solution;

[0041] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0042] Example 3 Antibacterial drug-loaded patch

[0043] formula:

[0044]

[0045] Preparation method:

[0046] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, freeze and thaw repeatedly for 3 times at -10°C for 4 h, add costusroot volatile oil and EGCG-pectin complex after thawing to room temperature, mix well, add deionized water to the full amount, mix well, and sonicate for 10 min to obtain the drug-containing gel solution;

[0047] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0048] Example 4 Antibacterial drug-loaded patch

[0049] formula:

[0050]

[0051] Preparation method:

[0052] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, repeat freezing and thawing 4 times at -5°C for 5 h, add costusroot volatile oil and EGCG-pectin complex after thawing to room temperature, mix well, add deionized water to the full amount, mix well, and sonicate for 5 min to obtain the drug-containing gel solution;

[0053] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0054] Example 5 Antibacterial drug-loaded patch

[0055] formula:

[0056]

[0057] Preparation method:

[0058] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, freeze and thaw twice at -15°C for 2 h, add costusroot volatile oil and EGCG-pectin complex after thawing to room temperature, mix well, add deionized water to the full amount, mix well, and sonicate for 15 min to obtain drug-containing gel solution;

[0059] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0060] Comparative Example 1 Antibacterial drug-loaded patch

[0061] formula:

[0062]

[0063] Preparation method:

[0064] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, freeze and thaw repeatedly for 3 times at -10°C for 4 h, add EGCG-pectin complex after thawing to room temperature, mix well, add deionized water to the full amount, mix well, and sonicate for 10 min to obtain drug-containing gel solution;

[0065] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0066] Comparative Example 2 Antibacterial drug-loaded patch

[0067] formula:

[0068]

[0069] Preparation method:

[0070] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, freeze and thaw repeatedly for 3 times at -10°C for 4 h. After thawing to room temperature, add costus root volatile oil and EGCG-pectin complex, mix well, add deionized water to the full amount, mix well, and sonicate for 10 min to obtain drug-containing gel solution;

[0071] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0072] Comparative Example 3 Antibacterial drug-loaded patch

[0073] formula:

[0074]

[0075] Preparation method:

[0076] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add Artemisia capillaris extract while stirring, freeze and thaw repeatedly for 3 times at -10°C for 4 hours, and after thawing to room temperature, add costus root volatile oil and pectin solution (pectin (Merck, P9135) is added to 0.01 mol / l phosphate buffer solution, placed in a 53°C water bath and stirred for 30-40 minutes to prepare a 20 mg / ml pectin solution), mix well, add deionized water to the full amount, mix well, and sonicate for 10 minutes to obtain a drug-containing gel solution;

[0077] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0078] Comparative Example 4 Antibacterial drug-loaded patch

[0079] formula:

[0080]

[0081] Preparation method:

[0082] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add Artemisia capillaris extract while stirring, freeze and thaw repeatedly for 3 times at -10°C for 4 hours, and after thawing to room temperature, add costus root volatile oil and GA-pectin complex (pectin (Merck, P9135) is added to 0.01 mol / l phosphate buffer solution, placed in a 53°C water bath and stirred for 30-40 minutes to prepare a 20 mg / ml pectin solution; 35 mmol / l GA (gallic acid) solution is added to the pectin solution while stirring to obtain a GA-pectin complex), mix well, add deionized water to the full amount, mix well, and ultrasonicate for 10 minutes to obtain a drug-containing gel solution;

[0083] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0084] Comparative Example 5 Antibacterial drug-loaded patch

[0085] formula:

[0086]

[0087] Preparation method:

[0088] (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, freeze at -5°C for 3 h and then melt at room temperature, add costus root volatile oil and EGCG-pectin complex, mix well, add deionized water to the full amount, mix well, and sonicate for 10 min to obtain a drug-containing gel solution;

[0089] (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

[0090] Damaged skin repair experiment

[0091] New Zealand rabbits were randomly divided into a model group, Example 1 group, Example 2 group, Example 3 group, Example 4 group, Example 5 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, and Comparative Example 4 group, with 3 rabbits in each group. The middle of the back of the New Zealand rabbits was depilated, and the depilation range was 5cm×5cm. The skin was damaged at the depilated area with a sterilized No. 400 fine sandpaper, and the skin was punctured to form a skin abrasion model with the appearance of dense bleeding points and bleeding. The corresponding drug-loaded patches of each example and comparative example group were applied to the skin abrasion sites of the grouped New Zealand rabbits, and the drugs were continuously administered for 5 days. The model group was applied with normal saline.

[0092] The density of bleeding points, the degree of bleeding, the degree of redness and swelling, and the degree of absence of scab were used as scoring indicators. Each indicator was divided into 0 to 5 points according to the degree. The skin reaction was observed under natural light 5 days after administration and the score was calculated.

[0093] Figure 1 The skin reaction scores of the New Zealand rats in each group after administration were obtained. The skin of the New Zealand rabbits in Example 1, Example 2, Example 3, Example 4, and Example 5 groups was well repaired with low irritation and high safety, and the redness, swelling, and blood spots were greatly reduced, and scabs appeared, which was significantly different from the model group.

[0094] Transdermal permeability test

[0095] Using a transdermal instrument, the treated SD rat abdominal skin was fixed between the supply pool and the receiving pool, with the stratum corneum facing the supply pool, and the stratum corneum was applied with the same area of ​​Example 1, Example 2, Example 3, Example 4, Example 5, Comparative Example 1, Comparative Example 2, Comparative Example 3, Comparative Example 4, and Comparative Example 5 drug-loaded patches, and the receiving solution was 20% ethanol-pH 7.4 phosphate buffer. Samples were taken at intervals and the corresponding volume of the receiving solution was supplemented. The samples were filtered with a 0.22 μm microporous membrane, and the contents of chlorogenic acid and parahydroxyacetophenone in the receiving solution were determined, and the cumulative permeation amount of each example was calculated according to the formula.

[0096] ) / A

[0097] Where V is the total volume of the receiving solution, Cn is the drug concentration measured at the nth sampling point (μg / mL), C is the drug concentration measured at the ith sampling point (μg / mL), V is the sampling volume, and A is the diffusion permeation area (cm 2 ).

[0098] Table 2 Cumulative permeation of drug-loaded patches (μg / cm 2 )

[0099]

[0100] Table 2 is the statistics of the cumulative permeation of some effective ingredients of the drug-loaded patches of Examples 1 to 5 and Comparative Examples 1 to 5, indicating that the improvement of costus root volatile oil and pectin pressure-sensitive adhesive materials can promote the skin permeability of drugs, increase the local drug concentration in the skin, promote wound healing and play an antibacterial role.

[0101] Antibacterial effect of antibacterial drug-loaded patches

[0102] The antibacterial ability of the antibacterial drug-loaded patches of Examples 1 to 5 and Comparative Examples 1 to 4 was evaluated, and experiments were conducted using Streptococcus pyogenes, Staphylococcus aureus, and Escherichia coli as strains.

[0103] Figure 2 The antibacterial ability of the antibacterial drug-loaded patches of Examples 1 to 5 and Comparative Examples 1 to 4 includes Streptococcus pyogenes, Staphylococcus aureus, and Escherichia coli, indicating that the antibacterial drug-loaded patch of the present invention has a higher antibacterial effect.

Claims

1. An antibacterial drug-carrying patch for repairing skin, characterized in that: The antibacterial drug-loaded patch for repairing skin is composed of a drug-containing glue and a membrane cloth; the drug-containing glue is calculated by mass fraction as follows: 2.5% to 6.5% of costusroot volatile oil, 0.8% to 2.8% of capillaris extract, 1.0% to 3.0% of hyaluronic acid, 10% to 20% of glycerol, an appropriate amount of deionized water, and 15% to 25% of EGCG-pectin complex; the membrane cloth is composed of a backing material and a protective layer; The preparation method of the EGCG-pectin complex is as follows: pectin is added to a 0.01 mol / l buffer solution, placed in a 50-55° C. water bath and stirred for 30-40 min to prepare a 20 mg / ml pectin solution; 35 mmol / l EGCG solution was added to the pectin solution with stirring to obtain an EGCG-pectin complex; In the Artemisia capillaris extract: the content of chlorogenic acid is not less than 1.0%, and the content of p-hydroxyacetophenone is not less than 0.10%; The method for preparing the antibacterial drug-loaded patch for repairing skin comprises the following steps: (1) Dissolve glycerol and hyaluronic acid in an appropriate amount of deionized water, add the Artemisia capillaris extract while stirring, freeze and thaw repeatedly 2 to 4 times, add costusroot volatile oil and EGCG-pectin complex after melting to room temperature, mix well, add deionized water to the full amount, mix well, and sonicate for 5 to 15 minutes to obtain the drug-containing gel solution; (2) Apply the drug-containing adhesive evenly on the surface of the backing material, dry it, cover it with a protective layer, punch it, and package it.

2. The antibacterial drug-carrying patch for repairing skin according to claim 1, characterized in that: The drug-containing gelatin solution is calculated by mass fraction as follows: 3.5% costusroot volatile oil, 1.9% capillaris extract, 1.5% hyaluronic acid, 12% glycerol, appropriate amount of deionized water, and 16% EGCG-pectin complex.

3. The antibacterial drug-carrying patch for repairing skin according to claim 1, characterized in that: The drug-containing gel solution is calculated by mass fraction as follows: 4.5% costusroot volatile oil, 1.6% capillaris extract, 2.0% hyaluronic acid, 13% glycerol, appropriate amount of deionized water, and 19% EGCG-pectin complex.

4. The antibacterial drug-carrying patch for repairing skin according to claim 1, characterized in that: The drug-containing gelatin solution is calculated by mass fraction as follows: 5.5% costusroot volatile oil, 2.5% capillaris extract, 2.5% hyaluronic acid, 17% glycerol, appropriate amount of deionized water, and 22% EGCG-pectin complex.

5. The antibacterial drug-carrying patch for repairing skin according to claim 1, characterized in that: The buffer solution is a phosphate buffer solution, a citrate buffer solution or a carbonate buffer solution.

6. The antibacterial drug-carrying patch for repairing skin according to claim 1, characterized in that: The freezing temperature in the freeze-thaw step is -10°C ± 5°C and the time is 2 to 5 hours.

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