Preparation method of skin application and skin application

Abstract

The invention relates to a skin application and a preparation method thereof.The skin application comprises a glue film and a functional layer, the functional layer is arranged on the glue film, the preparation method of the functional layer comprises the steps that 1, vitamins and a carrier solution are mixed to form a mixed solution, the vitamins comprise fat-soluble vitamins and / or water-soluble vitamins, the carrier is a high-molecular polymer, and the mixed solution is mixed with the carrier solution to form a mixed solution; the high-molecular polymer is selected from one or a combination of more of polylactic acid, polyvinyl alcohol, polyacrylate, polyacrylamide, polyethylene oxide and polycaprolactone; and (2) spinning the mixed solution by adopting an electrostatic spinning method to form a dry functional layer. According to the skin application, the nanofiber functional layer prepared through electrostatic spinning is loaded with vitamins, the functional layer and the adhesive film are attached to form the skin application, the skin application is directly attached to the skin, when the skin on the surface layer of the human body slightly sweats, the functional layer can be dissolved, the vitamins are absorbed into the human body through the skin, oral taking is not needed, and the skin application is safe and effective.

Description

Technical Field

[0001] The invention belongs to the field of skin application, and in particular relates to a preparation method of the skin application and the skin application. Background Art

[0002] Vitamin, sometimes transliterated as vitamin, is a special term in nutrition. It refers to a series of organic compounds. It is a kind of trace organic substance that humans and animals need to maintain normal physiological functions. Most of them cannot be produced by organisms themselves and must be taken from food. Only a few can be synthesized in the body or produced by intestinal microorganisms. It plays an important role in the growth, metabolism and development of the human body. It is one of the six major nutrients of the human body (sugar, fat, protein, inorganic salt, vitamin, water). Vitamins neither participate in the formation of human cells nor provide energy for the human body, but participate in biochemical reactions in the human body and regulate the metabolic function of the human body. If vitamin intake is insufficient, it will cause the human body's metabolism to lose balance, lead to decreased immunity, and cause "vitamin deficiency". Among them, due to lack of vitamins in food or reduced meal intake, insufficient intake can cause primary vitamin deficiency. The body's ability to absorb vitamins is reduced, the body's vitamin requirement is increased, or the interference of some drugs can lead to secondary vitamin deficiency.

[0003] For children, childhood is a critical period of physical and intellectual development, and vitamin supplementation is very important for the healthy growth of children. The following are the advantages of vitamin supplementation for children:

[0004] 1. Promote growth and development. Vitamins are essential substances for the growth and development of the body. For example, vitamin A contributes to the development of vision and the immune system, and vitamin D contributes to bone health. 2. Enhance immunity. Antioxidants such as vitamin C and vitamin E can help children resist diseases and enhance the function of the immune system. 3. Maintain normal physiological functions: B vitamins contribute to energy production and metabolism, and have a positive effect on children's vitality and mental state. 4. Promote the health of the nervous system. Certain vitamins, such as vitamin B12 and folic acid, are essential for the health of the nervous system. 5. Prevent anemia. Vitamin B12 and folic acid are important for red blood cells. 1. Vitamin C deficiency is very important for the formation of calcium, and a lack of these vitamins may lead to anemia; 2. Promote skin and hair health. Vitamin A and vitamin E have a positive effect on the health of skin and hair; 3. Improve appetite. Certain vitamins, such as vitamin B group 6, can help improve appetite; 4. Promote calcium absorption. Vitamin D helps calcium absorption and is essential for the development of children's bones; 5. Prevent diseases. Vitamin supplementation can help prevent certain diseases such as scurvy (vitamin C deficiency) and rickets (vitamin D deficiency); 6. Improve learning ability. Some studies have shown that appropriate vitamin supplementation may help improve children's learning ability and attention.

[0005] However, some children fail to develop good eating habits, resulting in an imbalance in vitamin intake and causing related physical discomfort symptoms. Summary of the invention

[0006] The purpose of the invention is to provide a preparation method of a skin patch.

[0007] The present invention also provides a skin patch prepared by the preparation method of the skin patch.

[0008] In order to achieve the above object, a technical solution adopted by the present invention is:

[0009] A method for preparing a skin patch, the skin patch comprising an adhesive film and a functional layer, the functional layer being arranged on the adhesive film, the method for preparing the functional layer comprising:

[0010] (1) vitamins and a carrier solution are mixed to form a mixed solution, wherein the vitamins include fat-soluble vitamins and / or water-soluble vitamins, and the carrier is a high molecular polymer, and the process is carried out at room temperature;

[0011] (2) The mixed solution is spun by an electrostatic spinning method to form a dry functional layer.

[0012] According to some preferred aspects of the present invention, in step (1), the mass ratio of the vitamin to the high molecular weight polymer is (5-25):(75-95).

[0013] According to some preferred aspects of the present invention, in step (1), the high molecular polymer is a combination of one or more selected from polylactic acid (PLA), polyvinyl alcohol (PVA), polyacrylate (PAA), polyacrylamide (PAM), polyethylene oxide (PEO), and polycaprolactone (PCL). The advantages of high molecular polymers are good biocompatibility, no irritation, medical use, and non-toxicity.

[0014] According to some preferred aspects of the present invention, in step (1), the high molecular polymer is selected from polyvinyl alcohol (PVA), polyacrylate (PAA), polyacrylamide (PAM), polyethylene oxide (PEO), has good hydrophilicity, and the functional layer needs to be soluble in water, so that it can begin to dissolve under the condition of slight sweating of the human body, release the carried vitamins, and enable them to be better absorbed by the skin.

[0015] According to some preferred aspects of the present invention, in step (1), the vitamins include fat-soluble vitamins, and the method for preparing the vitamins includes: dissolving the fat-soluble vitamins in a solvent and then adding cyclodextrin, wherein the solvent includes caprylic / capric triglyceride.

[0016] According to some preferred aspects of the present invention, in step (1), after obtaining the vitamins, the vitamin powder is prepared by spray drying.

[0017] According to some preferred aspects of the present invention, in step (1), the mass ratio of the fat-soluble vitamin, the solvent and the cyclodextrin is 1:(0.5-1):(0.5-1).

[0018] According to some preferred aspects of the present invention, in step (1), the vitamins include fat-soluble vitamins and water-soluble vitamins, and the method for preparing the vitamins includes: dissolving the fat-soluble vitamins in a solvent, adding cyclodextrin, and then adding water-soluble vitamins and water to obtain the vitamins, wherein the solvent includes caprylic / capric triglyceride.

[0019] According to some preferred aspects of the present invention, the mass ratio of the fat-soluble vitamin, the solvent, the water-soluble vitamin, and the cyclodextrin is (0.5-1): (0.5-1): (1-10): (0.5-1).

[0020] According to some preferred aspects of the present invention, the mass ratio of the fat-soluble vitamins, the solvent, the water-soluble vitamins, and the cyclodextrin is 1:1:(1-10):1.

[0021] According to some preferred aspects of the present invention, the method further comprises a penetration-enhancing substance. In step (1), vitamins, high molecular weight polymers and penetration-enhancing substances are mixed to form a mixed solution. The penetration-enhancing substance is a combination of one or more of small molecule collagen and small molecule hyaluronic acid. Considering the effect of epidermal absorption, when the vitamins and high molecular weight polymers are mixed and then spun to prepare a functional layer, the nanofiber structure is prepared. This structure enables the small amount of small molecule vitamins carried to be absorbed through the skin. In order to further enhance the effect of transdermal absorption, small molecule collagen or small molecule hyaluronic acid, which are substances widely present in the skin, are compounded to achieve a synergistic effect.

[0022] According to some preferred aspects of the present invention, the molecular weight of small molecule collagen is less than or equal to 3000 kDa; the molecular weight of small molecule hyaluronic acid is less than or equal to 10000 kDa.

[0023] According to some preferred aspects of the present invention, in step (1), the mass ratio of the high molecular weight polymer, vitamin and penetration enhancing substance is (60-70):30:(2-10).

[0024] According to some preferred aspects of the present invention, in step (1), the water-soluble vitamins include vitamin C and a combination of one or more of vitamin B group. Preferably, the vitamin B group includes a combination of one or more of vitamin B group 1, vitamin B group 2, vitamin B group 6, and vitamin B group 12.

[0025] According to some preferred aspects of the present invention, in step (1), the fat-soluble vitamins include a combination of one or more of vitamin A, vitamin D, vitamin E, and vitamin K.

[0026] According to some preferred aspects of the present invention, in step (1), the vitamins include vitamin A, vitamin B group, vitamin C, and vitamin E, and the mass ratio of vitamin A: vitamin B group: vitamin C: vitamin E is (1-2.25):(1.5-4.5):(25-100):(10-25).

[0027] According to some preferred aspects of the present invention, in step (1), after obtaining the vitamin mixture, the vitamin powder is prepared by spray drying.

[0028] According to some preferred aspects of the present invention, the cyclodextrin is selected from hydroxypropyl β-cyclodextrin (HPCD), methyl beta-cyclodextrin, hydroxypropyl beta-cyclodextrin azelaic acid or hydroxypropyl beta-cyclodextrin salicylate.

[0029] Cyclodextrin (CD) is a cyclic oligosaccharide compound formed by 6-12 D-glucose molecules connected by 1,4-glycosidic bonds. It has a hollow cylindrical structure with a hydrophilic exterior and a hydrophobic interior cavity. The embedding of compounds is mainly affected by the hydrophobic interaction between the cyclodextrin cavity and the guest molecule. This cavity can absorb hydrophobic small molecules or groups of a certain size and shape to form a stable non-covalent complex. The cyclodextrin cavity is hydrophobic, and the higher the non-polarity of the guest molecule, the easier it is to be included. When the hydrophobic and lipophilic guest molecule enters the cyclodextrin cavity, its hydrophobic group has the maximum contact with the cyclodextrin cavity, while its hydrophilic group is far away from the cavity.

[0030] By utilizing this structural feature, hydrophobic vitamins such as vitamin A and vitamin E can be encapsulated, thereby protecting these encapsulated vitamins from light and oxidative decomposition, and providing a host-guest encapsulation with controlled release characteristics through molecular encapsulation, so that fat-soluble vitamin raw materials can be dissolved in water. Active vitamins can also promote transdermal absorption of ingredients after being encapsulated by cyclodextrin. The main penetration-promoting mechanism is that cyclodextrin can increase the distribution coefficient of active substances in the stratum corneum of the skin, and can rearrange the stratum corneum-like corneous cells of the skin, making it easier for cyclodextrin to pass through, thereby promoting an increase in the transdermal rate of active substances.

[0031] According to some preferred aspects of the present invention, in step (2), the parameters of the electrospinning are: voltage range is 20-25 kV, and spinning distance range is 10-15 cm.

[0032] According to some preferred aspects of the present invention, in step (2), the dispersion and stirring are carried out for a long time to ensure uniform loading of the vitamins, and the dispersion is carried out in a closed container away from light to minimize the loss of the vitamins, wherein the time is 12-36 hours, preferably 24 hours.

[0033] To achieve the above object, another technical solution adopted by the present invention is:

[0034] A skin patch prepared by the above-mentioned preparation method of the skin patch.

[0035] According to some preferred aspects of the present invention, the skin patch further comprises a protective layer, and the functional layer is disposed between the adhesive film and the protective layer.

[0036] According to some preferred aspects of the present invention, the vitamins include vitamin A, vitamin B group, vitamin C, and vitamin E. For one skin application, the weight of the vitamin A is 0.2-0.45 mg, the weight of the vitamin B group is 0.3-0.9 mg, the weight of the vitamin C is 5-20 mg, and the weight of the vitamin E is 2-5 mg.

[0037] According to some preferred aspects of the present invention, the skin patch can be continuously applied to the skin for 1-8 hours.

[0038] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0039] The skin patch provided by the present invention uses a high molecular polymer as a carrier, carries vitamins, and then is prepared into a nanofiber functional layer through electrostatic spinning, and then is bonded with an adhesive film to form a skin patch. The skin patch is directly applied on the skin. When the surface skin of the human body sweats slightly, the functional layer can be dissolved, so that the vitamins can be absorbed into the human body through the skin. Oral administration is not required, and it is safe and effective, so as to solve the nutritional deficiency symptoms caused by children's unwillingness to eat fruits and vegetables or vitamin tablets, improve children's vitamin intake, and reduce the burden of parenting for parents. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Attached Figure 1 A top view of the functional layer and the adhesive film of the skin patch of the present invention;

[0041] Attached Figure 2 A top view of the protective layer of the skin patch of the present invention;

[0042] Attached Figure 3 A front view of the skin patch of the present invention;

[0043] Attached Figure 4 A photo of the reverse side of the skin patch of the present invention;

[0044] Attached Figure 5 A photograph showing the tearable layer of the skin patch of the present invention being torn off from a first perspective;

[0045] Attached Figure 6 A photograph showing the tearable layer of the skin patch of the present invention being torn off from a second viewing angle;

[0046] Attached Figure 7 A photograph of the skin patch of the present invention attached to the skin;

[0047] Attached Figure 8 The recommended daily intake of vitamins.

[0048] In the above attached figure:

[0049] 1-functional layer; 2-adhesive film; 3-fixing layer; 4-tearable layer. DETAILED DESCRIPTION

[0050] The present invention is further described below in conjunction with the illustrated embodiments.

[0051] Example 1

[0052] Vitamin A, vitamin B group, vitamin C and vitamin E are selected, and the mass ratio of vitamin A, vitamin B group, vitamin C and vitamin E is 1:1.5:25:10.

[0053] Polyvinyl alcohol (PVA) was selected as the high molecular polymer and was purchased from Kuraray with model number 4488.

[0054] The penetration-enhancing substance used was collagen, which was purchased from Shanghai Ruiyun.

[0055] The preparation process of the functional layer is as follows:

[0056] (1) Preparing a high molecular weight polymer and vitamins. The preparation process of the high molecular weight polymer is as follows: adding PVA while rapidly stirring cold water, and after the PVA particles are evenly dispersed, heating to 90° C., keeping the temperature for 1-2 hours, and rapidly stirring. After the PVA is completely dissolved, maintaining the stirring speed, cooling to room temperature, stopping stirring, defoaming, and setting aside to obtain a PVA solution, wherein the weight ratio of deionized water to PVA is 90:10.

[0057] The vitamin preparation process is: dissolve the fat-soluble vitamins in caprylic acid / capric acid triglycerides, then add cyclodextrin for encapsulation, and then dissolve them in water with water-soluble vitamins, and then use spray drying to prepare vitamin powder, wherein the ratio of fat-soluble vitamins, caprylic acid / capric acid triglycerides, water-soluble vitamins, and cyclodextrin is 1:1:5:1.

[0058] Next, use magnetic stirring to stir the PVA solution, vitamins, and penetration-enhancing substances in a light-proof, sealed container at a weight ratio of 60:30:10 for 24 hours to ensure uniform dispersion. After the mixture is defoamed, it is set aside for later use.

[0059] (2) Use electrospinning equipment for spinning, select a 25G needle, a voltage of 20-25kv, and a receiving distance of 10-15cm. The environmental conditions are: avoid light and keep the ambient humidity below 40%; continue spinning, and stop spinning when the film weight reaches 40g / ㎡. Cut the obtained film into 3*3cm size, and then laminate it with a film to obtain the final product skin patch, which is vacuum-sealed in an aluminum bag for storage.

[0060] Example 2

[0061] Vitamin A, vitamin B group, vitamin C and vitamin E are selected, and the mass ratio of vitamin A, vitamin B group, vitamin C and vitamin E is 1:1.5:25:10.

[0062] The high molecular weight polymer is polyethylene oxide (PEO), purchased from DuPont, with a molecular weight of 900 kDa.

[0063] The penetration-enhancing substance used was collagen, which was purchased from Shanghai Ruiyun.

[0064] The preparation process of the functional layer is as follows:

[0065] (1) Preparing a high molecular weight polymer and vitamins. The preparation process of the high molecular weight polymer is as follows: PEO is slowly added into deionized water under rapid stirring. After PEO is completely dissolved, stirring is stopped, and the solution is defoamed and set aside to obtain a PEO solution, wherein the mass ratio of deionized water to PEO is 95:5.

[0066] The vitamin preparation process is: dissolve the fat-soluble vitamins in caprylic acid / capric acid triglycerides, then add cyclodextrin for encapsulation, and then dissolve them in water with water-soluble vitamins, and then use spray drying to prepare vitamin powder, wherein the ratio of fat-soluble vitamins, caprylic acid / capric acid triglycerides, water-soluble vitamins, and cyclodextrin is 1:1:5:1.

[0067] Next, use magnetic stirring to stir the PEO solution, vitamins, and penetration-enhancing substances in a light-proof, sealed container at a weight ratio of 65:30:5 for 24 hours to ensure uniform dispersion. After the mixture is defoamed, it is set aside for later use.

[0068] (2) Use electrospinning equipment for spinning, select a 25G needle, a voltage of 20-25kv, and a receiving distance of 10-15cm. The environmental conditions are: avoid light and keep the ambient humidity below 40%; continue spinning, and stop spinning when the film weight reaches 40g / ㎡. Cut the obtained film into 3*3cm size, and then laminate it with a film to obtain the final product skin patch, which is vacuum-sealed in an aluminum bag for storage.

[0069] Example 3

[0070] Vitamin A, vitamin B group, vitamin C and vitamin E are selected, and the mass ratio of vitamin A, vitamin B group, vitamin C and vitamin E is 1:1.5:25:10.

[0071] Polyvinyl alcohol (PVA) was selected as the high molecular polymer and was purchased from Kuraray with model number 4488.

[0072] The penetration-enhancing substance used was small molecule hyaluronic acid, purchased from Freda Biotechnology.

[0073] The preparation process of the functional layer is as follows:

[0074] (1) Preparing a high molecular weight polymer and vitamins. The preparation process of the high molecular weight polymer is as follows: adding PVA while rapidly stirring cold water, and after the PVA particles are evenly dispersed, heating to 90° C., keeping the temperature for 1-2 hours, and rapidly stirring. After the PVA is completely dissolved, maintaining the stirring speed, cooling to room temperature, stopping stirring, defoaming, and setting aside to obtain a PVA solution, wherein the weight ratio of deionized water to PVA is 88:12.

[0075] The vitamin preparation process is: dissolve the fat-soluble vitamins in caprylic acid / capric acid triglycerides, then add cyclodextrin for encapsulation, and then dissolve them in water with water-soluble vitamins, and then use spray drying to prepare vitamin powder, wherein the ratio of fat-soluble vitamins, caprylic acid / capric acid triglycerides, water-soluble vitamins, and cyclodextrin is 1:1:5:1.

[0076] Next, use magnetic stirring to stir the PVA solution, vitamins and penetration-enhancing substances in a light-proof, sealed container at a weight ratio of 67:30:3 for 24 hours to ensure uniform dispersion. After the mixture is defoamed, it is set aside for later use.

[0077] (2) Use electrospinning equipment for spinning, select a 25G needle, a voltage of 20-25kv, and a receiving distance of 10-15cm. The environmental conditions are: avoid light and keep the ambient humidity below 40%; continue spinning, and stop spinning when the film weight reaches 40g / ㎡. Cut the obtained film into 3*3cm size, and then laminate it with a film to obtain the final product skin patch, which is vacuum-sealed in an aluminum bag for storage.

[0078] Example 4

[0079] Vitamin A, vitamin B group, vitamin C and vitamin E are selected, and the mass ratio of vitamin A, vitamin B group, vitamin C and vitamin E is 1:1.5:25:10.

[0080] The high molecular weight polymer is polyethylene oxide (PEO), purchased from DuPont, with a molecular weight of 900 kDa.

[0081] The penetration-enhancing substance used was small molecule hyaluronic acid, purchased from Freda Biotechnology.

[0082] The preparation process of the functional layer is as follows:

[0083] (1) Preparing a high molecular weight polymer and vitamins. The preparation process of the high molecular weight polymer is as follows: PEO is slowly added into deionized water under rapid stirring. After PEO is completely dissolved, stirring is stopped, and the solution is defoamed and set aside to obtain a PEO solution, wherein the mass ratio of deionized water to PEO is 94:6.

[0084] The vitamin preparation process is: dissolve the fat-soluble vitamins in caprylic acid / capric acid triglycerides, then add cyclodextrin for encapsulation, and then dissolve them in water with water-soluble vitamins, and then use spray drying to prepare vitamin powder, wherein the ratio of fat-soluble vitamins, caprylic acid / capric acid triglycerides, water-soluble vitamins, and cyclodextrin is 1:1:5:1.

[0085] Next, use magnetic stirring to stir the PEO solution, vitamins, and penetration-enhancing substances in a light-proof, sealed container at a weight ratio of 68:30:2 for 24 hours to ensure uniform dispersion. After the mixture is defoamed, it is set aside for later use.

[0086] (2) Use electrospinning equipment for spinning, select a 25G needle, a voltage of 20-25kv, and a receiving distance of 10-15cm. The environmental conditions are: avoid light and keep the ambient humidity below 40%; continue spinning, and stop spinning when the film weight reaches 40g / ㎡. Cut the obtained film into 3*3cm size, and then laminate it with a film to obtain the final product skin patch, which is vacuum-sealed in an aluminum bag for storage.

[0087] Example 5

[0088] Vitamin A, vitamin B group, vitamin C and vitamin E are selected, and the mass ratio of vitamin A, vitamin B group, vitamin C and vitamin E is 1:1.5:25:10.

[0089] Polyvinyl alcohol (PVA) was selected as the high molecular polymer and was purchased from Kuraray with model number 4488.

[0090] The preparation process of the functional layer is as follows:

[0091] (1) Preparing a high molecular weight polymer and vitamins. The preparation process of the high molecular weight polymer is as follows: adding PVA while rapidly stirring cold water, and after the PVA particles are evenly dispersed, heating to 90° C., keeping the temperature for 1-2 hours, and rapidly stirring. After the PVA is completely dissolved, maintaining the stirring speed, cooling to room temperature, stopping stirring, defoaming, and setting aside to obtain a PVA solution, wherein the weight ratio of deionized water to PVA is 90:10.

[0092] The vitamin preparation process is: dissolve the fat-soluble vitamins in caprylic acid / capric acid triglycerides, then add cyclodextrin for encapsulation, and then dissolve them in water with water-soluble vitamins, and then use spray drying to prepare vitamin powder, wherein the ratio of fat-soluble vitamins, caprylic acid / capric acid triglycerides, water-soluble vitamins, and cyclodextrin is 1:1:5:1.

[0093] Next, use magnetic stirring to stir the PVA solution and vitamins in a light-proof, sealed container at a weight ratio of 60:40 for 24 hours to ensure uniform dispersion. After completion, defoam and set aside.

[0094] (2) Use electrospinning equipment for spinning, select a 25G needle, a voltage of 20-25kv, and a receiving distance of 10-15cm. The environmental conditions are: avoid light and keep the ambient humidity below 40%; continue spinning, and stop spinning when the film weight reaches 40g / ㎡. Cut the obtained film into 3*3cm size, and then laminate it with a film to obtain the final product skin patch, which is vacuum-sealed in an aluminum bag for storage.

[0095] Example 6

[0096] In this example, only fat-soluble vitamins are selected, namely vitamin A and vitamin E, and the mass ratio of vitamin A to vitamin E is 1:10.

[0097] Polyvinyl alcohol (PVA) was selected as the high molecular polymer and was purchased from Kuraray with model number 4488.

[0098] The penetration-enhancing substance used was collagen, which was purchased from Shanghai Ruiyun.

[0099] The preparation process of the functional layer is as follows:

[0100] (1) Preparing a high molecular weight polymer and vitamins. The preparation process of the high molecular weight polymer is as follows: adding PVA while rapidly stirring cold water, and after the PVA particles are evenly dispersed, heating to 90° C., keeping the temperature for 1-2 hours, and rapidly stirring. After the PVA is completely dissolved, maintaining the stirring speed, cooling to room temperature, stopping stirring, defoaming, and setting aside to obtain a PVA solution, wherein the weight ratio of deionized water to PVA is 90:10.

[0101] The vitamin preparation process is: after dissolving the fat-soluble vitamin in caprylic acid / capric acid triglyceride, cyclodextrin is added, and then the vitamin powder is prepared by spray drying, wherein the ratio of the fat-soluble vitamin, caprylic acid / capric acid triglyceride, and cyclodextrin is 1:1:1.

[0102] Next, use magnetic stirring to stir the PVA solution, vitamins, and penetration-enhancing substances in a light-proof, sealed container at a weight ratio of 60:30:10 for 24 hours to ensure uniform dispersion. After the mixture is defoamed, it is set aside for later use.

[0103] (2) Use electrospinning equipment for spinning, select a 25G needle, a voltage of 20-25kv, and a receiving distance of 10-15cm. The environmental conditions are: avoid light and keep the ambient humidity below 40%; continue spinning, and stop spinning when the film weight reaches 40g / ㎡. Cut the obtained film into 3*3cm size, and then laminate it with a film to obtain the final product skin patch, which is vacuum-sealed in an aluminum bag for storage.

[0104] The cyclodextrin in Examples 1-6 is hydroxypropyl β-cyclodextrin (HPCD).

[0105] Example 7

[0106] In this example, only water-soluble vitamins are selected, including vitamin B complex and vitamin C, and the mass ratio of vitamin B complex to vitamin C is 1.5:25.

[0107] Polyvinyl alcohol (PVA) was selected as the high molecular polymer and was purchased from Kuraray with model number 4488.

[0108] The penetration-enhancing substance used was collagen, which was purchased from Shanghai Ruiyun.

[0109] The preparation process of the functional layer is as follows:

[0110] (1) Preparing a high molecular weight polymer and vitamins. The preparation process of the high molecular weight polymer is as follows: adding PVA while rapidly stirring cold water, and after the PVA particles are evenly dispersed, heating to 90° C., keeping the temperature for 1-2 hours, and rapidly stirring. After the PVA is completely dissolved, maintaining the stirring speed, cooling to room temperature, stopping stirring, defoaming, and setting aside to obtain a PVA solution, wherein the weight ratio of deionized water to PVA is 90:10.

[0111] The vitamin preparation process is: dissolving water-soluble vitamins in water to obtain vitamins, wherein the mass ratio of the water-soluble vitamins to water is 1:0.5.

[0112] Next, use magnetic stirring to stir the PVA solution, vitamins, and penetration-enhancing substances in a light-proof, sealed container at a weight ratio of 60:30:10 for 24 hours to ensure uniform dispersion. After the mixture is defoamed, it is set aside for later use.

[0113] (2) Use electrospinning equipment for spinning, select a 25G needle, a voltage of 20-25kv, and a receiving distance of 10-15cm. The environmental conditions are: avoid light and keep the ambient humidity below 40%; continue spinning, and stop spinning when the film weight reaches 40g / ㎡. Cut the obtained film into 3*3cm size, and then laminate it with a film to obtain the final product skin patch, which is vacuum-sealed in an aluminum bag for storage.

[0114] Comparative Example 1

[0115] Vitamin A, vitamin B group, vitamin C and vitamin E are selected, and the mass ratio of vitamin A, vitamin B group, vitamin C and vitamin E is 1:1.5:25:10.

[0116] Polyvinyl alcohol (PVA) was selected as the high molecular polymer and was purchased from Kuraray with model number 4488.

[0117] The penetration-enhancing substance used was collagen, which was purchased from Shanghai Ruiyun.

[0118] The preparation process of the functional layer is as follows:

[0119] (1) Prepare high molecular polymer and vitamins. The preparation process of high molecular polymer is as follows: add PVA while rapidly stirring cold water, and after the PVA particles are evenly dispersed, heat up to 90° C., keep warm for 1-2 hours, and rapidly stir. After the PVA is completely dissolved, maintain the stirring speed, cool to room temperature, stop stirring, defoam and set aside. The weight ratio of deionized water to PVA is 90:10.

[0120] The vitamin preparation process is: vitamin A, vitamin B group, vitamin C and vitamin E are added into water to obtain vitamins.

[0121] Next, use magnetic stirring to stir the mixed PVA solution, vitamins, and penetration-enhancing substances in a light-proof, sealed container at a weight ratio of 60:30:10 for 24 hours to ensure uniform dispersion. After the mixture is defoamed, it is set aside for later use.

[0122] After defoaming, water-oil separation was found and subsequent spinning was impossible, proving that simply mixing the vitamin raw materials was not feasible.

[0123] Comparative Example 2

[0124] Compared with Example 6, cyclodextrin was not selected, and vitamin A and vitamin E were selected, and the mass ratio of vitamin A to vitamin E was 1:10.

[0125] Polyvinyl alcohol (PVA) was selected as the high molecular polymer and was purchased from Kuraray with model number 4488.

[0126] The penetration-enhancing substance used was collagen, which was purchased from Shanghai Ruiyun.

[0127] The preparation process of the functional layer is as follows:

[0128] (1) Prepare high molecular polymer and vitamins. The preparation process of high molecular polymer is as follows: add PVA while rapidly stirring cold water, and after the PVA particles are evenly dispersed, heat up to 90° C., keep warm for 1-2 hours, and rapidly stir. After the PVA is completely dissolved, maintain the stirring speed, cool to room temperature, stop stirring, defoam and set aside. The weight ratio of deionized water to PVA is 90:10.

[0129] The vitamin preparation process is as follows: fat-soluble vitamin E is dissolved in caprylic acid / capric acid triglyceride to form vitamins, thereby obtaining vitamins.

[0130] Next, use magnetic stirring to stir the mixed PVA solution, vitamins, and penetration-enhancing substances in a light-proof, sealed container at a weight ratio of 60:30:10 for 24 hours to ensure uniform dispersion. After the mixture is defoamed, it is set aside for later use.

[0131] Since the vitamins prepared in step (1) in this example are separated into water and oil, they are insoluble in each other and cannot be spun.

[0132] The performance tests of the functional layers of Examples 1-7 and Comparative Examples 1-2 were performed as follows:

[0133] 1. Comparison of spinning efficiency

[0134] The functional layers of Examples 1-7 and Comparative Examples 1-2 were compared under the same spinning conditions in terms of the time taken to reach the final spinning weight and the surface quality of Examples 1-7 and Comparative Examples 1-2.

[0135] Table 1 Time taken to reach the final spinning weight and surface quality data in Examples 1-7 and Comparative Examples 1-2

[0136]

[0137] 2. Test of trace element content in film layer

[0138] The functional layer of Example 1 was tested for trace vitamins and the test was entrusted to Ningbo Customs Technical Center.

[0139] Table 2 Detection data of trace vitamins in the functional layer of Example 1

[0140]

[0141] Judging from the test results, trace elements can be encapsulated in fibers through electrospinning, which proves that it is feasible to encapsulate trace elements through this method.

[0142] 3. Transdermal absorption test

[0143] This test selected the treated pigskin for the test, and the specific method was as follows: the pigskin stratum corneum was laid flat on the diffusion cell with the stratum corneum facing upward and fixed, and a certain amount of epidermal water was sprayed with a spray to simulate human sweating. The functional layer sample of Example 1 was applied to the isolated pigskin, and a receiving solution (PBS buffer solution with pH 7.0-7.4) was added to the receiving cell, and the liquid surface just contacted the bottom surface of the skin. The device was placed in a (32±1)℃ constant temperature water bath, and stirred continuously with a magnetic stirrer with a stirring speed of 300r / min. The receiving solution at 0h, 2h, 4h, and 8h after contact was taken as the test solution, and the test solution was taken for detection by an ultraviolet spectrophotometer, and then the transdermal absorption time was used to draw a graph of the transdermal absorption concentration, and the absorption law of the test substance could be obtained through the curve.

[0144] After the penetration is completed, the samples to be tested at each time point on the skin, in the skin, and under the skin of different experimental groups and the blank control solution are tested. The specific processing methods are as follows:

[0145] 1) Test of the unpenetrated part of the skin: After 24 hours, use a 1 mL pipette to take PBS and repeatedly blow it to clean the skin surface. Wash 5 times for a total of 5 mL. Collect all the washing liquid and place it in a 5 mL centrifuge tube for testing;

[0146] 2) Test of the skin: Use a sterile scalpel to cut the skin along the inner edge of the supply chamber, cut the skin into pieces, add 5 mL of PBS buffer and ultrasonically extract for 60 minutes. After the ultrasonication is completed, centrifuge and take the supernatant for testing;

[0147] 3) Subcutaneous part test: At each time point, 2 mL of receiving solution was drawn from the receiving chamber and placed in a 2 mL centrifuge tube for testing. The content of vitamin B group 6 was tested according to the method described above.

[0148] Data Analysis:

[0149] A: Cumulative penetration

[0150] Q=Cn×V+Ci(i=1...n-1)×V0

[0151] In the above formula, Q is the cumulative permeation amount; V is the volume of the receiving liquid in the receiving chamber, specifically 8.5 mL; V0 is the volume of each sampling, specifically 2 mL; Ci is the drug concentration in the receiving liquid during the 1st to n-1st samplings; Cn is the sample concentration measured at the nth sampling point; Ckbn is the concentration measured at the nth blank control sampling point.

[0152] B: Diffusion percentage

[0153] P=Q / Po×100%

[0154] In the above formula, P is the diffusion percentage; Q is the cumulative permeation amount of the sample in the receiving chamber at each time point; Po is the content of the loaded sample.

[0155] C: Permeability coefficient

[0156] A regression equation was made with the cumulative penetration amount (Y axis) versus the penetration time (X axis), and the slope of the equation was the transdermal coefficient Kp (penetration rate).

[0157] D: Recovery rate

[0158] Recovery rate = total content (skin+skin+subcutaneous) / sample amount × 100%.

[0159] The transdermal absorption test results of the functional layer of Example 1 are shown in Table 2.

[0160] Table 2 Transdermal absorption test results of the functional layer of Example 1

[0161]

[0162] As can be seen from the above table, each vitamin can successfully penetrate the skin, among which fat-soluble vitamins have a higher penetration rate.

[0163] Another embodiment of the present invention provides a skin patch prepared by the above-mentioned skin patch preparation method, comprising an adhesive film 2, a functional layer 1, and a protective layer, wherein the functional layer 1 is disposed between the adhesive film 2 and the protective layer, wherein one side of the adhesive film 2 is sticky, the sticky side of the adhesive film 2 is opposite to the protective layer, and the functional layer 1 is bonded to the sticky side of the adhesive film 2; the protective layer comprises a fixing layer 3 and a tearable layer 4, wherein the fixing layer 3 and the tearable layer 4 are separated by a cutting line, the fixing layer 3 is located at the edge, and the tearable layer 4 is attached to the functional layer 1, wherein the surface area of ​​the tearable layer 4 is greater than the surface area of ​​the fixing layer 3. When the skin patch is used, the tearable layer 4 is torn off along the cutting line to expose the functional layer 1, and then the adhesive film 2 is attached to the skin, and the fixing layer 3 is removed after the functional layer 1 is attached to the skin, and the functional layer 1 is waited to be absorbed by the skin.

[0164] The advantages of this skin patch are:

[0165] 1. Using electrospinning technology, with high molecular polymer as carrier, a variety of trace vitamins are carried to prepare a nanofiber functional layer. The functional layer is made of nanofibers loaded with vitamins, and then the functional layer is bonded to the film to form a skin patch. The skin patch is directly applied on the skin. When the surface skin of the human body sweats slightly, the functional layer can be dissolved, allowing the trace elements to be absorbed into the human body through the skin; the skin patch can be continuously applied on the skin for 1-8 hours.

[0166] By utilizing electrospinning technology, a completely dry functional membrane layer can be produced, which is easier to store, and no preservatives or additives that are irritating to the skin need to be added to the original solution. In addition, since the nanofiber material prepared by the electrospinning process has a larger specific surface area and porosity, it can load the effective ingredients more efficiently while also enhancing the penetration of the effective ingredients and improving the penetration and absorption rate of the effective ingredients, while also ensuring good air permeability.

[0167] 2. The functional layer has good mechanical properties. When polyvinyl alcohol (PVA) is used as the polymer, the fiber membrane formed by electrospinning has better mechanical properties. When polyethylene oxide (PEO) is used as the polymer, the fiber membrane formed by electrospinning has better flexibility and stretchability. When prepared into a skin patch, it can be better shaped and easier to store.

[0168] 3. The selected high molecular polymer has good hydrophilicity, good biocompatibility, no irritation, medical use, and no toxicity. When applied to the skin, when the human body sweats slightly, the film layer can be dissolved by the skin sweat, so that the trace vitamins in it can better penetrate the skin and be absorbed; further compounding of penetration-promoting substances can enhance the effect of transdermal absorption.

[0169] 4. When preparing vitamins, process them at room temperature to reduce the loss of vitamins. Fat-soluble vitamins or water-soluble vitamins do not require high-temperature heating, which will not affect the activity of the vitamins.

[0170] 5. As children's skin is usually very delicate and easily irritated, medical pressure-sensitive adhesives that do not have pharmacological effects and are not absorbed by the human body are selected to achieve the adhesive function while ensuring the adhesion. At the same time, the protective layer is breathable and hygroscopic to avoid discomfort to the skin being adhered and is non-irritating.

[0171] 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 the technology to understand the content of the present invention and implement it accordingly, and 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 method for preparing a skin patch, the skin patch comprising a film and a functional layer, characterized in that: The functional layer is disposed on the adhesive film, and the preparation method of the functional layer includes: (1) vitamins and a carrier solution are mixed to form a mixed solution, wherein the vitamins include fat-soluble vitamins and / or water-soluble vitamins, the carrier is a high molecular polymer, and the high molecular polymer is a combination of one or more selected from polylactic acid, polyvinyl alcohol, polyacrylate, polyacrylamide, polyethylene oxide, and polycaprolactone; (2) The mixed solution is spun by an electrostatic spinning method to form a dry functional layer.

2. The method for preparing the skin patch according to claim 1, characterized in that: In step (1), the vitamins include fat-soluble vitamins, and the preparation method of the vitamins includes: dissolving the fat-soluble vitamins in a solvent and then adding cyclodextrin, wherein the solvent includes caprylic / capric triglyceride.

3. The method for preparing the skin patch according to claim 2, characterized in that: In step (1), after obtaining the vitamin, a spray drying method is used to prepare vitamin powder; and\or in step (1), the mass ratio of the fat-soluble vitamin, the solvent and the cyclodextrin is 1:(0.5-1):(0.5-1).

4. The method for preparing the skin patch according to claim 2, characterized in that: The vitamins also include water-soluble vitamins. The preparation method of the vitamins includes: dissolving the fat-soluble vitamins in a solvent, adding cyclodextrin, and then adding water-soluble vitamins and water to obtain the vitamins, wherein the solvent includes caprylic / capric triglyceride.

5. The method for preparing the skin patch according to claim 4, characterized in that: The mass ratio of the fat-soluble vitamin, the solvent, the water-soluble vitamin and the cyclodextrin is (0.5-1):(0.5-1):(1-10):(0.5-1).

6. The method for preparing a skin patch according to claim 1, characterized in that: The vitamins include water-soluble vitamins. The preparation method of the vitamins includes: dissolving the water-soluble vitamins in water to obtain the vitamins, and the mass ratio of the water-soluble vitamins to water is 1:(0.5-1).

7. The method for preparing a skin patch according to claim 1, characterized in that: The mass ratio of the vitamin to the high molecular weight polymer is (5-25):(75-95).

8. The method for preparing a skin patch according to claim 1, characterized in that: In step (1), a penetration-enhancing substance is added to the mixed solution, wherein the penetration-enhancing substance is a combination of one or more of collagen and hyaluronic acid.

9. The method for preparing a skin patch according to claim 8, characterized in that: In step (1), the mass ratio of the high molecular weight polymer, vitamin and penetration enhancing substance is (60-70):30:(2-10); and\or, In step (1), the water-soluble vitamins include a combination of one or more of vitamin C and vitamin B group; the fat-soluble vitamins include a combination of one or more of vitamin A, vitamin D, vitamin E, and vitamin K.

10. A skin patch prepared by the method for preparing a skin patch according to any one of claims 1 to 9.

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