Staged slow-release acne paste with composite structure

Abstract

The invention discloses a staged slow-release acne patch with a composite structure, the staged slow-release acne patch sequentially comprises a first layer, a second layer and a third layer, the first layer contains retinochrome, the second layer and the third layer are hydrocolloid, the hydrocolloid contains a functional material, and the functional material is a composite material. The release time of the functional material is controlled by adjusting the thickness of the second layer and the third layer and the content of water-absorbing macromolecules in the hydrocolloid, so that the release time is matched with the acne healing process, and the first layer is used for being attached to the skin. The staged sustained-release acne patch comprises a first layer containing a retinochrome, a second layer containing an antibacterial agent and / or a pore dredging agent, and a third layer containing an anti-inflammatory agent and / or a healing promoting agent, the acne patch is divided into three layers which are stacked up and down, and the thickness is adjusted, so that the acne patch can achieve a staged slow release effect, functional substances can be released in a targeted manner at different stages of an acne growth cycle, and acne healing is promoted.

Description

[0001] This application is a divisional application of the invention patent application with application date of July 28, 2022, application number 2022108984003, and invention name “Stage-release acne patch and preparation method thereof”. Technical Field

[0002] The invention belongs to the technical field of medical patch application, and in particular relates to a phased sustained-release acne patch with a composite structure. Background Art

[0003] Acne, also known as acne, is a chronic inflammatory skin disease of the pilosebaceous gland unit. Its clinical manifestations are characterized by polymorphic skin lesions such as acne, papules, pustules, and nodules that are prone to occur on the face. The occurrence of acne is closely related to factors such as excessive sebum secretion, blockage of the pilosebaceous gland ducts, bacterial infection, and inflammatory response. After entering puberty, the level of androgens in the human body, especially testosterone, rises rapidly, promoting the development of sebaceous glands and producing a large amount of sebum. At the same time, abnormal keratinization of the pilosebaceous gland duct causes blockage of the duct, obstruction of sebum discharge, and formation of keratin plugs, i.e., micro-acnes. Various microorganisms, especially Propionibacterium acnes, multiply in the hair follicles. The lipase produced by Propionibacterium acnes decomposes sebum to produce free fatty acids, while chemotacticizing inflammatory cells and mediators, ultimately inducing and aggravating the inflammatory response.

[0004] The growth cycle of acne is about 10-15 days, which can be divided into four stages: germination, growth, maturity and healing. Each stage lasts about 2-4 days. According to the advice of dermatologist Baumann, the method of systematic treatment of acne is divided into 5 steps:

[0005] 1. Normalize keratinization or keratin shedding and prevent keratinocytes that have already shed from sticking together.

[0006] 2. Eliminate or reduce Propionibacterium acnes and reduce the level of inflammatory extracellular products produced by Propionibacterium acnes.

[0007] 3. Remove substances that clog pores, loosen keratin and unblock pores.

[0008] 4. Use anti-inflammatory products to prevent inflammatory response and reduce acne lesions.

[0009] 5. Reduce the activity of sebaceous glands, thereby reducing sebum levels.

[0010] Existing acne care patches often have simple ingredients and structures, and can only target one or several stages of acne treatment. For example, Patent 202011536535.2 provides an antibacterial and anti-inflammatory acne patch, which adds antibacterial and anti-inflammatory substances such as chamomile, salicylic acid, and aloe vera, and has a good effect on bacterial inflammation, but cannot improve the problem of sebaceous gland blockage; or although complex functional ingredients are added, the corresponding ingredients cannot be released in a targeted manner according to the different stages of acne. For example, Patent 202011512112.7 adds substances with antibacterial and repair-promoting functions to the acne patch, but this invention does not have a structure for phased release, so the functional ingredients will be released at the same time, which cannot match the acne growth cycle. Summary of the invention

[0011] In view of this, in order to overcome the defects of the prior art, the purpose of the present invention is to provide a staged sustained-release acne patch, which adopts a composite structure containing different ingredients to achieve a staged sustained-release that matches the growth cycle of acne.

[0012] In order to achieve the above object, the present invention adopts the following technical solutions:

[0013] A staged sustained-release acne patch comprises a first layer, a second layer and a third layer in sequence, wherein the first layer contains visual pigments, the second layer and / or the third layer are hydrocolloids, the hydrocolloids in the second layer contain antibacterial agents and / or pore unclogging agents; the hydrocolloids in the third layer contain anti-inflammatory agents and / or healing agents, and the first layer is used to fit the skin. That is, the hydrocolloids in the second and third layers contain water-absorbing polymers, hot-melt pressure-sensitive adhesives and other functional materials such as antibacterial agents and / or pore unclogging agents, anti-inflammatory agents and / or healing agents.

[0014] The water-absorbing polymer is one or more selected from modified starch, gum arabic, gelatin, pectin, sodium polyacrylate, polyacrylamide, sodium carboxymethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and polyvinyl pyrrolidone; the hot-melt pressure-sensitive adhesive is one or more selected from natural rubber, polyurethane rubber, silicone rubber, polyisobutylene rubber, styrene block copolymer thermoplastic elastomer, polyacrylate, and polyvinyl ether.

[0015] According to some preferred embodiments of the present invention, the diameter of the first layer is smaller than that of the second layer, and the diameter of the third layer is equal to that of the second layer. The first layer is non-sticky and requires the hydrocolloid of the second layer to adhere to the skin, so the diameter of the first layer can only be smaller than that of the second layer.

[0016] According to some preferred implementation aspects of the present invention, the thickness of the first layer is 0.2-1 mm; the thickness of the second layer is 0.1-0.3 mm; the thickness of the third layer is 0.1-0.3 mm. The thickness of each layer is adjusted according to the release time of the functional substance, and there is no direct thickness relationship between the layers.

[0017] According to some preferred implementation aspects of the present invention, the mass proportion of visual pigment in the first layer is 1%-10%; the mass proportion of water-absorbing polymer in the second layer is 20%-40%, and the mass proportion of hot-melt pressure-sensitive adhesive is 60%-80%; the mass proportion of water-absorbing polymer in the third layer is 20%-40%, and the mass proportion of hot-melt pressure-sensitive adhesive is 60%-80%. The release of functional ingredients depends on the dissolution and gradual penetration and diffusion of functional ingredients after the hydrocolloid absorbs water. The content of water-absorbing polymer determines the rate of water absorption and the ability of the hydrocolloid to retain water, which in turn affects the penetration rate of the functional ingredients. Therefore, the sustained release of functional ingredients by hydrocolloid is achieved under the combined influence of the content of water-absorbing polymer and the thickness of the hydrocolloid layer.

[0018] According to some preferred implementation aspects of the present invention, the permeability coefficient of the second layer and / or the third layer is 70-350; the permeability coefficient is calculated as the value obtained by dividing the mass percentage of the water-absorbing polymer in the layer by the thickness of the layer. Permeability coefficient = content of water-absorbing polymer ÷ thickness of hydrocolloid layer, the permeability coefficient only has a value, no unit. The larger the permeability coefficient, the faster the release rate of the functional ingredients and the earlier the initial release time node. Under the premise of 20%-40% of the water-absorbing polymer content and 0.1-0.3mm of the hydrocolloid layer thickness, the permeability coefficient of each layer of the present invention is controlled between 70-350. When it is necessary to release the functional ingredients in the second and third layers as soon as possible, the permeability coefficient can be increased, that is, the thickness can be reduced and / or the content of water-absorbing polymer can be increased. By controlling the permeability coefficient, the release time of the functional substance is controlled to match the acne healing process.

[0019] According to some preferred embodiments of the present invention, a first substrate is provided on a side of the first layer away from the second layer, and a diameter of the first substrate is greater than or equal to a diameter of the second layer.

[0020] According to some preferred implementation aspects of the present invention, the diameter of the first layer is smaller than that of the second layer, and the first substrate has a groove for accommodating the first layer; the diameter of the first substrate is larger than that of the second layer.

[0021] According to some preferred implementation aspects of the present invention, a second substrate is arranged on a side of the third layer away from the second layer, and a diameter of the second substrate is greater than or equal to a diameter of the third layer.

[0022] Specifically, in some embodiments of the present invention, in order to facilitate production, sales and use, there are substrates on the upper and lower sides of the acne patch, wherein the first substrate contacts the first layer and the second layer, and the second substrate contacts the third layer. The first substrate is a release paper with a thickness of 25 to 45 μm and a diameter (slightly) larger than the second layer. There is a groove in the center, which is used to accommodate the first layer. The depth of the groove is (slightly) larger than the thickness of the first layer. The second substrate is a protective layer with a thickness of 5 to 25 μm and a diameter consistent with the third layer. There is also a tear line (dashed line) in the diameter direction of the first substrate, which is convenient for tearing when used.

[0023] According to some preferred embodiments of the present invention, the visual pigment is one or more selected from retinol, retinal, retinoic acid, retinamide, retinoic acid esters, and retinol esters; the antibacterial agent is one or more selected from azelaic acid, quaternary ammonium salts, aloe extract, Anemarrhena extract, costus root extract, tea extract, clindamycin, benzoyl peroxide, and erythromycin; the pore unclogging agent is one or more selected from salicylic acid, α-hydroxy acid, citric acid, and jojoba oil; the anti-inflammatory agent is one or more selected from dipotassium glycyrrhizinate, Stephania tetrandra extract, golden chamomile extract, comfrey extract, honeysuckle extract, and biological sugars; the healing agent is one or more selected from ginkgo leaf extract, niacinamide, Centella asiatica extract, healing velvet flower extract, and sea fennel extract.

[0024] According to some preferred embodiments of the present invention, the hydrocolloid in the second layer and / or the third layer contains a soothing agent; the soothing agent is one or more selected from menthol, menthol, tea tree essential oil, β-glucan, and allantoin.

[0025] The principle of the present application is as follows: The present application mainly includes a first layer containing visual pigments, a second layer containing antibacterial agents and / or pore unclogging agents, and a third layer containing anti-inflammatory agents and / or healing agents. It is divided into a three-layer design stacked up and down, and the thickness and composition are adjusted to match, so that the acne patch can achieve a staged sustained release effect. Specifically, the functional substance (visual pigment) in the first layer can be slowly dissolved and released when the acne patch is first used; the functional substances (antibacterial agents, pore unclogging agents, soothing agents, etc.) in the second layer are encapsulated in hydrocolloids and need to gradually diffuse to the outer layer, so there is a delay in release; the third layer is similar to the second layer, but the functional substances (anti-inflammatory agents, healing agents, soothing agents) need to penetrate thicker hydrocolloids (second and third layers), so the release rate is slower. By adjusting the thickness of the second and third layers and the content of water-absorbing polymers in the hydrocolloid, the release time of the functional substances can be controlled to match the acne healing process. The thickness of the second and third layers determines the penetration and diffusion distance of the functional substances in each layer, and the content of water-absorbing polymers determines the penetration rate of the functional ingredients. The combination of the two achieves the sustained release of the functional ingredients.

[0026] Among them, the visual pigments in the first layer can reduce the cell viscosity by reducing the positive and negative charges, and at the same time can reduce the level of transglutaminase responsible for the cross-linking of keratinocyte membrane proteins, preventing the detached keratinocytes from sticking together. In addition, it can also reduce the activity of sebaceous glands, which is suitable for the early stage of acne treatment.

[0027] The antibacterial substances (antibacterial agents) in the second layer can inhibit the proliferation of Propionibacterium acnes and reduce the level of inflammatory extracellular products produced by Propionibacterium acnes; combined with substances that unclog pores (pore uncloggers), such as salicylic acid, α-hydroxy acid and azelaic acid, they can remove acne dirt accumulated in the pores. These two types of substances can prevent acne from getting worse and are suitable for the growth stage of acne.

[0028] The third layer contains anti-inflammatory substances (anti-inflammatory agents) that can inhibit the production of inflammatory factors, reduce inflammation and relieve the pain caused by inflammation. In the final stage of treatment, substances that promote skin repair and reduce pigmentation (healing agents) can be used. These two types of substances are suitable for the mature and healing stages of acne.

[0029] Since acne is essentially a series of inflammatory reactions, accompanied by pain, burning sensation and other discomfort, some substances with soothing effects (soothing agents) can be added throughout the treatment stage to reduce the discomfort caused by the inflammatory reaction.

[0030] The present invention also provides a method for preparing the above-mentioned staged sustained-release acne patch, comprising the following steps:

[0031] 1) dissolving the visual pigment and the auxiliary materials in water, mixing them evenly and pouring them into a mold, drying them to obtain a soluble patch, which is used to form the first layer; or, mixing the solid powders of the visual pigment and the auxiliary materials evenly and making solid tablets with a tablet press to form the first layer; the auxiliary materials include excipients, thickeners, etc.;

[0032] 2) adding one or more of an antibacterial agent, a pore unclogging agent, a soothing agent, a water-absorbing polymer, and a hot-melt pressure-sensitive adhesive into a kneader and mixing them uniformly to obtain a hydrocolloid for forming a second layer;

[0033] 3) adding one or more of an anti-inflammatory agent, a healing agent, a soothing agent, a water-absorbing polymer, and a hot-melt pressure-sensitive adhesive into a kneader and mixing them uniformly to obtain a hydrocolloid for forming a third layer;

[0034] 4) The hydrocolloid used to form the second layer and the third layer is co-extruded through a double layer, and then calendered and die-cut with the soluble patch or pressed sheet used to form the first layer to obtain the staged sustained-release acne patch. In some embodiments, the acne patch has substrates on the upper and lower sides, so the hydrocolloid used to form the second layer and the third layer is co-extruded through a double layer, and then calendered and die-cut with the soluble patch or pressed sheet used to form the first layer, the first substrate below, and the second substrate above to obtain the staged sustained-release acne patch.

[0035] Due to the implementation of the above technical scheme, the present invention has the following advantages compared with the prior art: the staged sustained-release acne patch in the present invention comprises a first layer containing visual pigments, a second layer containing antibacterial agents and / or pore unclogging agents, and a third layer containing anti-inflammatory agents and / or healing promoters; it is divided into a three-layer design stacked up and down, and the thickness is adjusted to match, so that the acne patch can achieve a staged sustained-release effect, and can release functional substances in a targeted manner at different stages of the acne growth cycle to promote the healing of acne. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0037] Figure 1 This is a schematic diagram of the structure of a staged sustained-release acne patch in a preferred embodiment of the present invention;

[0038] Figure 2 This is a schematic diagram of the first substrate structure of the staged sustained-release acne patch in a preferred embodiment of the present invention;

[0039] In the drawings, first layer-1, second layer-2, third layer-3, first substrate-4, second substrate-5, groove-6, tear line-7. DETAILED DESCRIPTION

[0040] In order to enable those skilled in the art to better understand the technical solution of the present invention, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. 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 creative work should fall within the scope of protection of the present invention.

[0041] like Figure 1 and 2As shown, the staged sustained-release acne patch in this embodiment includes a first substrate, a first layer, a second layer, a third layer, and a second substrate in sequence. The first layer contains visual pigments, and the second layer and / or the third layer are hydrocolloids. The hydrocolloids in the second layer contain one or more of antibacterial agents, pore unclogging agents, and soothing agents; the hydrocolloids in the third layer contain one or more of anti-inflammatory agents, healing agents, and soothing agents. The first layer is used to fit the skin. That is, the hydrocolloids in the second and third layers contain water-absorbing polymers, hot-melt pressure-sensitive adhesives, and other functional materials such as antibacterial agents and / or pore unclogging agents, anti-inflammatory agents, and / or healing agents.

[0042] The mass proportion of visual pigments in the first layer is 1%-10%; the mass proportion of water-absorbing polymers in the second layer is 20%-40%, and the mass proportion of hot-melt pressure-sensitive adhesives is 60%-80%; the mass proportion of water-absorbing polymers in the third layer is 20%-40%, and the mass proportion of hot-melt pressure-sensitive adhesives is 60%-80%.

[0043] The diameter of the first layer is less than or equal to the diameter of the second layer, and the diameter of the third layer is greater than or equal to the diameter of the second layer. The diameter of the first substrate is greater than or equal to the diameter of the second layer, and the diameter of the second substrate is greater than or equal to the diameter of the third layer. The thickness of the first layer is less than or equal to the thickness of the second layer, and the thickness of the third layer is less than or equal to the thickness of the second layer. In this embodiment, the thickness of the first layer is 0.2-0.5mm; the thickness of the second layer is 0.1-0.3mm; the thickness of the third layer is 0.1-0.3mm. The permeability coefficient of the second layer and / or the third layer is 70-350; the permeability coefficient is calculated as the value obtained by dividing the mass percentage of the water-absorbing polymer in the layer by the thickness of the layer. By adjusting the thickness of the second layer and the third layer and the formula of the hydrocolloid (i.e., adjusting the permeability coefficient), the release time of the functional substance can be controlled to match the acne healing process.

[0044] When the diameter of the first layer is smaller than the diameter of the second layer, the first substrate is in contact with the first layer and the second layer. The first substrate is a release paper with a thickness of 25 to 45 μm and a diameter (slightly) larger than the second layer. There is a groove in the center, which is used to accommodate the first layer. The depth of the groove is (slightly) larger than the thickness of the first layer. The second substrate is a protective layer with a thickness of 5 to 25 μm and a diameter consistent with the third layer. There is also a tear line 7 (dashed line) in the diameter direction of the first substrate for easy tearing when in use.

[0045] The water-absorbing polymer is one or more selected from modified starch, gum arabic, gelatin, pectin, sodium polyacrylate, polyacrylamide, sodium carboxymethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and polyvinyl pyrrolidone; the hot-melt pressure-sensitive adhesive is one or more selected from natural rubber, polyurethane rubber, silicone rubber, polyisobutylene rubber, styrene block copolymer thermoplastic elastomer, polyacrylate, and polyvinyl ether. The visual pigment is one or more selected from retinol, retinal, retinoic acid, retinamide, retinoic acid ester, retinol ester; the antibacterial agent is one or more selected from azelaic acid, quaternary ammonium salt, aloe extract, Anemarrhena extract, costus root extract, tea extract, clindamycin, benzoyl peroxide, erythromycin; the pore unclogging agent is one or more selected from salicylic acid, α-hydroxy acid, citric acid, jojoba oil; the anti-inflammatory agent is one or more selected from dipotassium glycyrrhizinate, Stephania tetrandra extract, golden chamomile extract, lithospermum officinale extract, honeysuckle extract, biosaccharide; the healing agent is one or more selected from ginkgo leaf extract, niacinamide, Centella asiatica extract, healing velvet flower extract, sea fennel extract. The soothing agent is one or more selected from menthol, menthol, tea tree essential oil, β-glucan, and allantoin.

[0046] The preparation method of the above staged sustained-release acne patch comprises the following steps:

[0047] 1) Dissolving the visual pigment and the auxiliary materials in water, mixing them evenly, pouring them into a mold, and drying them to obtain a soluble patch, which is the first layer; or, mixing the solid powders of the visual pigment and the auxiliary materials evenly, and then using a tablet press to make a solid tablet, which is the first layer; the auxiliary materials include excipients, thickeners, etc.;

[0048] 2) adding one or more of an antibacterial agent, a pore unclogging agent, a soothing agent, a water-absorbing polymer, and a hot-melt pressure-sensitive adhesive into a kneader and mixing them uniformly to obtain a hydrocolloid, which is the second layer;

[0049] 3) adding one or more of an anti-inflammatory agent, a healing agent, a soothing agent, a water-absorbing polymer, and a hot-melt pressure-sensitive adhesive into a kneader and mixing them uniformly to obtain a hydrocolloid, which is the third layer;

[0050] 4) The hydrocolloids of the second and third layers are co-extruded through double layers, and then calendered and die-cut together with the soluble patch or pressed tablet of the first layer, the first substrate below and the second substrate above to obtain a staged sustained-release acne patch.

[0051] Example 1: Stage 1 sustained release acne patch

[0052] like Figure 1 and 2 As shown, the staged sustained-release acne patch in this embodiment includes a first substrate, a first layer, a second layer, a third layer, and a second substrate in sequence.

[0053] Among them, the first layer is prepared from 5% visual pigment, 90% excipient, and 5% thickener; the second and third layers are hydrocolloids; the second layer is prepared from 35% water-absorbing polymer, 60% hot-melt pressure-sensitive adhesive, 1% antibacterial agent, 2% pore unclogging agent, and 2% soothing agent; the third layer is prepared from 30% water-absorbing polymer, 60% hot-melt pressure-sensitive adhesive, 3% anti-inflammatory agent, 3% healing agent, and 4% soothing agent; the first layer is used for fitting to the skin.

[0054] The diameter of the first layer is 8mm, the diameter of the second layer is 12mm, the diameter of the third layer is 12mm, the diameter of the first substrate is 13mm, and the diameter of the second substrate is 12mm. The first substrate is a release paper, and its diameter is larger than the diameter of the second layer. The diameter of the first layer is smaller than the diameter of the second layer. The first substrate is in contact with the first layer and the second layer, and there is a groove in the center. The groove is used to accommodate the first layer, and the depth of the groove is greater than the thickness of the first layer. The second substrate is a protective layer, and its diameter is consistent with that of the third layer. There is also a tear line 7 (dashed line) in the diameter direction of the first substrate, which is convenient for tearing when used.

[0055] In this embodiment, the thickness of the first layer is 0.4 mm, the thickness of the second layer is 0.3 mm, and the thickness of the third layer is 0.3 mm. Correspondingly, in this embodiment, the permeability coefficient of the second layer is 117, and the permeability coefficient of the third layer is 100.

[0056] Example 2: Staged sustained release acne patch

[0057] The structure, composition and size of each layer of the staged sustained-release acne patch in this embodiment are the same as those in embodiment 1, except that the thickness of the second layer in this embodiment is 0.2 mm. Correspondingly, the permeability coefficient of the second layer in this embodiment is 175.

[0058] Example 3: Stage 3 sustained release acne patch

[0059] The structure and dimensions of each layer of the staged sustained-release acne patch in this embodiment are the same as those in embodiment 1, except that the water-absorbing polymer content in the second layer in this embodiment is 25%, and the hot melt adhesive content is 70%. Correspondingly, the permeability coefficient of the second layer in this embodiment is 83.

[0060] Example 4 Preparation method of stage sustained-release acne patch

[0061] The preparation method of the staged sustained-release acne patch corresponding to the above embodiment comprises the following steps:

[0062] 1) dissolving the visual pigment and the auxiliary materials in water, mixing them evenly and pouring them into a mold, drying them to obtain a soluble patch, which is used to form the first layer; or, mixing the solid powders of the visual pigment and the auxiliary materials evenly and making solid tablets with a tablet press to form the first layer; the auxiliary materials include excipients, thickeners, etc.;

[0063] 2) adding one or more of an antibacterial agent, a pore unclogging agent, a soothing agent, a water-absorbing polymer, and a hot-melt pressure-sensitive adhesive into a kneader and mixing them uniformly to obtain a hydrocolloid for forming a second layer;

[0064] 3) adding one or more of an anti-inflammatory agent, a healing agent, a soothing agent, a water-absorbing polymer, and a hot-melt pressure-sensitive adhesive into a kneader and mixing them uniformly to obtain a hydrocolloid for forming a third layer;

[0065] 4) The hydrocolloid used to form the second layer and the third layer is double-layer co-extruded, and then calendered and die-cut together with the soluble patch or pressed tablet used to form the first layer, the first substrate below and the second substrate above to obtain a staged sustained-release acne patch.

[0066] Comparative Example 1

[0067] The difference between this comparative example and Example 1 is that in this comparative example, the first layer, the second layer and the third layer except the substrate are combined into one layer, and the corresponding functional ingredients are all mixed in one layer. Specifically, this layer includes 2.4% of visual pigments, 31.7% of water-absorbing polymers, 58.5% of hot-melt pressure-sensitive adhesives, 0.5% of antibacterial agents, 1% of pore unclogging agents, 2.9% of soothing agents, 1.5% of anti-inflammatory agents, and 1.5% of healing agents.

[0068] Preparation method: Add visual pigments, antibacterial agents, pore unclogging agents, soothing agents, anti-inflammatory agents, healing agents, water-absorbing polymers, and hot-melt pressure-sensitive adhesives into a kneader and mix them evenly to obtain a hydrocolloid. After extrusion by a screw, the hydrocolloid is calendered and die-cut together with a first substrate below and a second substrate above to obtain an acne patch.

[0069] Comparative Example 2

[0070] The difference between this comparative example and Example 1 is that the second layer and the third layer in Example 1 are exchanged in this comparative example, that is, the second layer in this comparative example is the third layer in Example 1, and the third layer in this comparative example is the second layer in Example 1. The other formula components and preparation steps are basically the same as those in Example 1.

[0071] Comparative Example 3

[0072] The difference between this comparative example and Example 1 is that the first layer in this comparative example is prepared from 0.5% visual pigment, 94.5% excipient, and 5% thickener. The other formula ingredients and preparation steps are basically the same as those in Example 1.

[0073] Comparative Example 4

[0074] The difference between this comparative example and Example 1 is that the second layer in this comparative example is prepared from 10% water-absorbing polymer, 85% hot-melt pressure-sensitive adhesive, 1% antibacterial agent, 1% pore-unclogging agent, and 2% soothing agent. The other formula ingredients and preparation steps are basically the same as those in Example 1. Correspondingly, the permeability coefficient of the second layer in this example is 33.

[0075] Comparative Example 5

[0076] The difference between this comparative example and Example 1 is that the third layer in this comparative example is prepared from 15% water-absorbing polymer, 75% hot-melt pressure-sensitive adhesive, 3% anti-inflammatory agent, 3% healing agent, and 4% soothing agent. The other formula ingredients and preparation steps are basically the same as those in Example 1. Correspondingly, the permeability coefficient of the third layer in this example is 50.

[0077] Tests and Results

[0078] 1) Release percentage: Wet the filter paper with simulated body fluid, tear off the first substrate of the acne patch, and stick it on the wet filter paper to simulate the acne patch being applied on wet skin. Take out the filter paper every 3 days and extract it in purified water to detect the content of active substances in each layer. The results are shown in Table 1.

[0079] Table 1 Test results

[0080]

[0081]

[0082] It can be seen from the test results in Table 1 that the release cycle of the active substance in the hydrocolloid is related to the layer in which it is located, the thickness of the hydrocolloid layer, and the water-absorbing polymer content in the hydrocolloid. Compared with the second layer, the release cycle of the active substance in the third layer is relatively delayed; the smaller the thickness of the hydrocolloid and the greater the water-absorbing polymer content, the faster the release rate of the active substance. If all active substances are mixed in one layer (Comparative Example 1), all ingredients are released at the same time, and there is no staged sustained release function. In Comparative Example 4, due to the low water-absorbing polymer content and the low permeability coefficient, the release of the active substance in the second layer is too slow, which is not compatible with the acne healing process and has a poor treatment effect; the same is true for Comparative Example 5.

[0083] 2) Actual use effect: The acne patch samples were applied to the red and swollen areas of newly developed acne on the faces of volunteers, and the patches were removed after 12 days to observe the treatment effect on the acne areas. The results are shown in Table 2.

[0084] Table 2 Effect of use

[0085] sample Effects Example 1 No cysts or pustules, no pain when pressed, no nodules, and the redness and swelling have completely disappeared Example 2 No cysts or pustules, no pain when pressed, no nodules, and the redness and swelling have completely disappeared Example 3 No cysts or pustules, no pain when pressed, no nodules, and the redness and swelling have completely disappeared Comparative Example 1 No cysts or abscesses, slight pain when pressed, nodules, and some redness and swelling Comparative Example 2 No cysts or abscesses, no pain when pressed, slight nodules, redness and swelling have basically disappeared Comparative Example 3 No cysts or abscesses, no pain when pressed, slight nodules, redness and swelling have basically disappeared Comparative Example 4 No cysts or abscesses, no pain when pressed, slight nodules, redness and swelling have basically disappeared Comparative Example 5 No cysts or abscesses, no pain when pressed, slight nodules, redness and swelling have basically disappeared

[0086] It can be seen from the use effect in Table 2 that the release cycle of various active ingredients in Examples 1-3 matches the acne healing cycle, and the acne is completely healed after 12 days of use; Comparative Example 1 does not have a sustained release function, and the release cycle of the active ingredients in Comparative Examples 2-5 does not match the acne healing cycle, and the effect of promoting acne healing is not significant.

[0087] The present invention aims at the shortcomings of existing acne care patches, which have a single component structure and cannot release functional substances in stages, and designs a staged sustained-release acne patch with a composite structure. The functional components of the acne patch in the present invention can cover all stages of acne treatment, and the release time of the functional components can be regulated by adjusting the thickness of each layer to match the stage of acne. Specifically, the staged sustained-release acne patch of the present invention is composed of a three-layer structure, namely a first layer in direct contact with the skin, a second layer that is bonded to the first layer in the center and in direct contact with the skin at the periphery, and a third layer as the outermost layer. The first layer is a soluble patch or a pressed tablet containing visual pigment components and other excipients (excipients, thickeners, etc.). The second layer is a hydrocolloid patch, which is composed of a water-absorbing polymer, a hot-melt pressure-sensitive adhesive, an antibacterial agent, a pore dredging agent, and a soothing agent. The diameter is slightly larger than the first layer and the thickness is 0.1-0.3mm. The third layer is a hydrocolloid patch, which is composed of a water-absorbing polymer, a hot-melt pressure-sensitive adhesive, an anti-inflammatory agent, a healing promoter, and a soothing agent. It has the same diameter as the second layer and a thickness of 0.1-0.3mm. The functional substances in the first layer can be slowly dissolved and released when the acne patch is first used; the functional substances in the second layer are encapsulated in the hydrocolloid and need to gradually diffuse to the outer layer, so there is a delay in release; the third layer is similar to the second layer, but the functional substances need to penetrate a thicker hydrocolloid, so the release rate is slower. By adjusting the thickness of the second and third layers and the formula of the hydrocolloid, the time of release of the functional substances can be controlled to match the healing process of acne. The staged sustained-release acne patch in this application: a variety of functional ingredients are added to correspond to all stages of the acne growth treatment cycle; the main body is a multi-layer structure, which can achieve staged sustained release of functional ingredients; by adjusting the thickness of each layer, the release of functional ingredients can be matched with the growth treatment cycle of acne.

[0088] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with this technology to understand the contents of the present invention and implement them accordingly. They cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A phased sustained-release acne patch with a composite structure, characterized in that: The invention comprises a first layer, a second layer and a third layer in sequence, wherein the first layer contains visual pigments, the second layer and the third layer are hydrocolloids, and the hydrocolloids contain functional materials. The release time of the functional materials is controlled by adjusting the thickness of the second layer and the third layer and the content of the water-absorbing polymer in the hydrocolloid to match the acne healing process, and the first layer is used to fit the skin.

2. The phased sustained-release acne patch according to claim 1, characterized in that: The thickness of the first layer is less than or equal to the thickness of the second layer, and the thickness of the third layer is less than or equal to the thickness of the second layer.

3. The phased sustained-release acne patch according to claim 2, characterized in that: The thickness of the first layer is 0.2-1 mm; the thickness of the second layer is 0.1-0.3 mm; and the thickness of the third layer is 0.1-0.3 mm.

4. The phased sustained-release acne patch according to claim 1, characterized in that: The hydrocolloids in the second layer and the third layer include water-absorbing polymers and hot-melt pressure-sensitive adhesives.

5. The phased sustained-release acne patch according to claim 1, characterized in that: The mass proportion of the water-absorbing polymer in the second layer is 20%-40%, and the mass proportion of the hot-melt pressure-sensitive adhesive in the second layer is 60%-80%; and / or, The mass proportion of the water-absorbing polymer in the third layer is 20%-40%, and the mass proportion of the hot-melt pressure-sensitive adhesive in the third layer is 60%-80%.

6. The phased sustained-release acne patch according to claim 1, characterized in that: Under the premise that the water-absorbing polymer content in the hydrocolloid is 20%-40% and the hydrocolloid layer thickness is 0.1-0.3mm, the permeability coefficients of the second and third layers are 70-350; the permeability coefficient is calculated as the value obtained by dividing the mass percentage of the water-absorbing polymer in the layer by the thickness of the layer.

7. The phased sustained-release acne patch according to claim 1, characterized in that: The visual pigment in the first layer accounts for 1%-10% by weight.

8. The phased sustained-release acne patch according to claim 4, characterized in that: The functional material contained in the hydrocolloid of the second layer is an antibacterial agent and / or a pore-clearing agent; and / or, The functional material contained in the hydrocolloid of the third layer is an anti-inflammatory agent and / or a healing agent; and / or, The hydrocolloid of the second layer and / or the third layer contains a soothing agent.

9. The phased sustained-release acne patch according to claim 8, characterized in that: The water-absorbing polymer is one or more selected from modified starch, gum arabic, gelatin, pectin, sodium polyacrylate, polyacrylamide, sodium carboxymethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, and polyvinyl pyrrolidone; and / or, The hot melt pressure sensitive adhesive is one or more selected from natural rubber, polyurethane rubber, silicone rubber, polyisobutylene rubber, styrene block copolymer thermoplastic elastomer, polyacrylate, polyethylene ether; and / or, The visual pigment is one or more selected from retinol, retinal, retinoic acid, retinamide, retinoic acid ester, retinol ester; the antibacterial agent is one or more selected from azelaic acid, quaternary ammonium salt, aloe extract, Anemarrhena extract, costusroot extract, tea extract, clindamycin, benzoyl peroxide, erythromycin; and / or, The pore unclogging agent is selected from one or more of salicylic acid, α-hydroxy acid, citric acid, and jojoba oil; the anti-inflammatory agent is selected from one or more of dipotassium glycyrrhizinate, Stephania tetrandra extract, golden chamomile extract, comfrey extract, honeysuckle extract, and biological sugar; and / or, The healing promoting agent is one or more selected from the group consisting of ginkgo leaf extract, niacinamide, Centella asiatica extract, velvetleaf flower extract, and sea fennel extract; The soothing agent is one or more selected from menthol, menthol, tea tree essential oil, β-glucan, and allantoin.

10. The phased sustained-release acne patch according to claim 1, characterized in that: The diameter of the first layer is smaller than or equal to the diameter of the second layer, and the diameter of the third layer is larger than or equal to the diameter of the second layer.

11. The phased sustained-release acne patch according to claim 1, characterized in that: comprising a first substrate disposed on a side of the first layer away from the second layer, wherein a diameter of the first substrate is greater than or equal to a diameter of the second layer; and / or, The method comprises arranging a second substrate on a side of the third layer away from the second layer, wherein a diameter of the second substrate is greater than or equal to a diameter of the third layer.

12. The phased sustained-release acne patch according to claim 11, characterized in that: The diameter of the first layer is smaller than the diameter of the second layer. The first substrate has a groove for accommodating the first layer. The depth of the groove is greater than the thickness of the first layer.

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