Medicine for removing birthmarks

Abstract

The invention discloses a medicine for removing birthmarks and belongs to the technical field of traditional Chinese medicine compositions, and the core of the medicine is compound medicine powder prepared by the invention, namely a traditional Chinese medicine formula. The main mechanism of removing birthmarks is that a plurality of links such as melanin synthesis, maturation, transportation, degradation and discharge are inhibited, and specifically, the birthmarks can be removed by inhibiting enzymes (mainly tyrosinase) required by melanin generation, destroying melanocytes, reducing dopaquinone and the like. Wherein tyrosinase is proved to be a main rate-limiting enzyme in a melanin biosynthetic pathway, and most of substances which can decolorize skin and have a whitening effect block generation of skin melanin by inhibiting the activity of the tyrosinase so as to achieve the whitening effect. The radix angelicae, the radix ampelopsis, the rhizoma atractylodis macrocephalae, the white poria, the rhizoma bletillae, the herba asari and the rhizoma typhonii in the traditional Chinese medicine formula provided by the invention have an inhibiting effect on the activity of tyrosinase, and synthesis of skin melanin can be reduced by inhibiting the activity of the tyrosinase.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine compositions, and in particular relates to a medicine for removing birthmarks. Background Art

[0002] Birthmark is a common skin disease. If the birthmark grows on the face, it affects the individual's appearance. Some birthmarks may also cause other diseases.

[0003] The main causes of birthmarks are: 1. Environmental pollution is one of the main causes of birthmarks. After being stimulated by the external polluted environment, the human body will show different manifestations, and birthmarks are one of them; 2. Although genetic factors are generally believed to be the main factors causing the formation of birthmarks, there is no conclusive scientific basis so far. Some biologists also believe that the cause of birthmarks is the mutation of chromosomes in human evolution, which is then reflected in human skin through inheritance; 3. Due to the lack of certain nutrients such as calcium, iron, zinc, magnesium and other trace elements and phenylalanine, tyrosine, etc., the human body can easily affect the biochemical process of pigment synthesis, resulting in abnormal increase in pigment secretion by pigment cells, and through nerve conduction to the epidermis, gradually spreading, and forming birthmarks; 4. Living environment, mainly refers to the acquired environment. Due to certain bad problems in personal lifestyle, such as long-term irregular eating, irregular personal life and uncontrolled overeating, it is possible to stimulate the body under certain conditions, thus forming birthmarks.

[0004] Commonly used external treatment methods include gold ring friction to remove birthmarks, cryotherapy, isotope therapy, skin grafting, laser scanning, etc. These methods have long treatment cycles, unobvious effects, and large side effects. Most importantly, they only treat the symptoms and not the root cause. Summary of the invention

[0005] The purpose of the present invention is to provide a medicine for removing birthmarks to solve the problems in the background technology.

[0006] The purpose of the present invention can be achieved through the following technical solutions: A medicine for removing birthmarks is prepared by the following steps: S1, crushing the medicinal materials and passing them through a 120-mesh sieve, and then mixing them to obtain a composite medicinal powder; S2. Place honey in a ceramic container, heat it to 105-115° C. over high heat, then switch to low heat and continue heating to 116-118° C., heat at a constant temperature for 20-40 seconds, then continue heating at a low heat to 119-122° C., add maltose and beeswax, stir at a constant temperature until the beeswax melts, and stir at a constant temperature for 2-5 minutes to obtain a matrix, and pour the matrix into a stainless steel container while it is hot; S3. When the temperature of the matrix in the stainless steel container is naturally cooled to 60-70°C, add the composite powder thereinto, stir until the temperature drops to 40-45°C, then add the transdermal agent and salt thereinto, and continue stirring for 20-50 minutes to obtain the birthmark removing drug.

[0007] Furthermore, the mass ratio of the honey, maltose, beeswax, composite powder, transdermal agent and salt is 50:6-7:15:50:2:1.

[0008] Furthermore, the transdermal agent is prepared by the following steps: Methanol is added to a reaction container, and piperine and activated carbon-supported palladium catalyst are then added thereto with stirring. After the addition is completed, nitrogen is filled into the reaction container to replace the air inside the reaction container, and hydrogen is then filled into the reaction container to replace the nitrogen inside the reaction container. The hydrogen replacement of the gas in the reaction container is repeated three times. The reaction container is filled with hydrogen to 2.0-2.2 MPa for the last time. After completion, the reaction container is heated to 115-125° C. again, and stirred at a constant temperature for reaction for 2-4 hours. After completion of the reaction, the reaction container is naturally cooled to room temperature to obtain a product, and the product is filtered to recover the activated carbon-supported palladium catalyst, and the filtrate is collected. An adsorbent is then added to the filtrate with stirring, and the mixture is stirred at room temperature for 20-30 minutes, and the adsorbent is removed by filtration to obtain an impurity-removed product. The impurity-removed product is then subjected to reduced pressure distillation to remove the solvent methanol, and a solid component is collected. The solid component is then washed with pure water for three times, filtered, and the solid component is dried to a constant weight under a constant temperature of 40-50° C. to obtain a transdermal agent.

[0009] Furthermore, the palladium content of the activated carbon-supported palladium catalyst is 10%.

[0010] Furthermore, the usage ratio of the methanol, piperine and activated carbon-supported palladium catalyst is 400 mL:50 g:2.5-3.0 g.

[0011] Furthermore, the amount of the adsorbent used accounts for 4% to 10% of the mass of the filtrate.

[0012] Furthermore, the adsorbent is prepared by the following steps: A1. Take methanol as solvent, add Zn(NO3)2·6H2O and CuSO4·5H2O into it, and stir ultrasonically for 20-50 min to obtain a clear Cu / Zn solution; A2, take the solvent methanol, add 2-methylimidazole thereto, and stir ultrasonically for 20 to 50 minutes to obtain a 2-methylimidazole-methanol solution; A3. Pour the Cu / Zn solution into the 2-methylimidazole-methanol solution and stir ultrasonically for 4 to 5 hours to obtain a blue mixed solution. Centrifuge the mixed solution to collect the solid component, wash the solid component three times with methanol, and dry the washed solid component at a constant temperature of 40 to 50° C. to constant weight to obtain an adsorbent.

[0013] Furthermore, the usage ratio of methanol, Zn(NO3)2·6H2O and CuSO4·5H2O in A1 is 0.5L:20mmol:1mmol.

[0014] Furthermore, the usage ratio of methanol and 2-methylimidazole in A2 is 0.5L:14-15g.

[0015] Furthermore, the volume ratio of the Cu / Zn solution and the 2-methylimidazole-methanol solution in A3 is 1:1.

[0016] Furthermore, the composite medicinal powder comprises the following raw materials in parts by mass: 20 parts of Angelica dahurica, 20 parts of Bletilla striata, 20 parts of Atractylodes macrocephala, 20 parts of Poria cocos, 20 parts of Astragalus membranaceus, 10 parts of Bombyx batryticatus, 10 parts of Bletilla striata, 10 parts of Leonurus japonicus, 1 part of Asarum, 1 part of Radix et Rhizoma Cyperi, 1 part of Pearl Powder, and 1 part of Syringa obovata.

[0017] Furthermore, the composite medicinal powder also includes the following raw materials in parts by mass: 10 parts of bupleurum, 12 parts of angelica, 15 parts of red peony root, 12 parts of cyperus, 15 parts of salvia miltiorrhiza, 15 parts of safflower, and 15 parts of rose. Adding the aforementioned Chinese medicinal ingredients can further enhance the therapeutic effect for those suffering from liver depression and blood stasis.

[0018] Furthermore, the composite medicinal powder also includes the following raw materials in parts by weight: 20 parts of Codonopsis pilosula, 15 parts of Rehmannia root, 15 parts of jujube, 6 parts of Licorice, 10 parts of Chuanxiong, and 10 parts of Aucklandia root. Adding the aforementioned Chinese medicinal ingredients can further enhance the therapeutic effect for those with weak Qi and blood.

[0019] Furthermore, the composite medicinal powder also includes the following raw materials in parts by mass: 15 parts of Rehmannia root, 15 parts of Lycium barbarum, 15 parts of Cuscuta seed, 12 parts of Ligustrum lucidum fruit, 15 parts of Eclipta prostrata, 15 parts of processed Polygonum multiflorum, 10 parts of Cornus officinalis, and 12 parts of Dioscorea opposita. Adding the aforementioned Chinese medicinal ingredients can further enhance the therapeutic effect for those with kidney yin deficiency.

[0020] Furthermore, the composite medicine powder also includes the following raw materials in parts by mass: 6 parts of cinnamon twig and 10 parts of Morinda officinalis. Adding the aforementioned Chinese medicinal ingredients can further enhance the therapeutic effect for those with kidney yang deficiency.

[0021] Beneficial effects of the present invention: The present invention provides a medicine for removing birthmarks, and the effective core of the medicine is a composite powder prepared by the present invention, i.e., a Chinese medicine formula. The main mechanism of removing birthmarks is to inhibit the synthesis, maturation, transportation, degradation, and discharge of melanin, which can be achieved by inhibiting the enzymes (mainly tyrosinase) required for melanin production, destroying melanocytes, and reducing dopaquinone. Among them, tyrosinase has been confirmed to be the main rate-limiting enzyme in the biosynthetic pathway of melanin. Most of the substances that can decolorize the skin and have whitening effects are to block the production of skin melanin by inhibiting the activity of the enzyme to achieve the whitening effect. The angelica dahurica, white scutellaria, white atractylodes, white tuckahoe, white schizonepeta, asarum, and white aconite in the Chinese medicine formula provided by the present invention all have an inhibitory effect on tyrosinase activity, and the synthesis of skin melanin can be reduced by inhibiting tyrosinase activity.

[0022] Specifically, the Atractylodes macrocephala in the Chinese medicine formula provided by the present invention is used as the main medicine, which is good at treating weak spleen and stomach qi and dark skin caused by malnutrition, and is a key medicine for whitening. White Poria is a ministerial medicine, which assists Atractylodes macrocephala in nourishing the spleen and replenishing qi. Bletilla striata can nourish fur, promote tissue regeneration and reduce swelling. It is used together with Bletilla striata, which is a key medicine for sore astringent and tissue regeneration. Moreover, Bletilla striata is lubricating and sticky in nature, and can adhere to various medicines. It is an excipient, so that the medicine can be more fully absorbed and penetrated into the skin after application, and play a therapeutic and nutritional role; Angelica dahurica can dispel wind and dampness, discharge pus, and promote blood circulation, and can help Atractylodes macrocephala to promote qi and promote fragrance, and can also promote skin metabolism and delay aging; Asarum is good at wandering and entering the qi, promoting metabolism; Bombyx batryticatus dispels wind, calms the liver, softens the liver, eliminates spots and dredges the meridians; these five medicines (Bletilla striata, Bletilla striata, Angelica dahurica, Asarum and Bombyx batryticatus) are adjuvants. White aconite leads the medicine upward, and the medicine penetrates deep into the skin, which can accelerate the absorption of the medicine.

[0023] Further, the medicine for removing birthmarks prepared by the present invention adopts the mode of plaster, adds precious Chinese medicine ingredients such as pearl powder and white cloves, can effectively penetrate into the skin, achieve the effects of promoting blood circulation and removing blood stasis, dredging meridians, promoting qi and blood, and promoting the metabolism of epithelial tissue cells, and astragalus and motherwort play the role of invigorating qi and promoting blood circulation, and dredging meridians. Wherein, the present invention is added with a homemade transdermal agent, further improving the permeability of Chinese medicine components to the skin, the homemade transdermal agent of the present invention is tetrahydropiperine prepared by hydrogenation of piperine, tetrahydropiperine can promote the rapid and effective penetration of natural ingredients, so that the absorption and utilization of skin tissue to the functional ingredients is significantly improved and promoted, and can assist the rapid penetration of the drug functional ingredients into the skin. In order to further improve the purity of tetrahydropiperine, the present invention uses a homemade adsorbent to purify the product of piperine after hydrogenation. Specifically, the self-made adsorbent of the present invention is a ZIF-8 (zeolite imidazolate framework-8) material carrying Cu, and the adsorbent contains abundant copper ions and zinc ions. The copper ions can form coordination bonds with the carbon-carbon double bonds on piperine, thereby realizing the adsorption of unreacted piperine in the hydrogenation product; according to the Dewar-Chatt-Duncanson model, there is a synergistic interaction between zinc ions and carbon-carbon double bonds, that is, the π orbital of the carbon-carbon double bond provides electrons to the zinc ions, and at the same time, the zinc ions perform π-back-bonding to the π* orbital of the carbon-carbon double bond, thereby realizing the adsorption of the carbon-carbon double bond.

[0024] Finally, after testing, it was found that the birthmark removal drug of the present invention can reduce melanocyte proliferation and whiten the skin, with obvious efficacy and few side effects. DETAILED DESCRIPTION

[0025] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions 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 making creative work are within the scope of protection of the present invention.

[0026] Example 1

[0027] Preparation of adsorbent: A1. Take 0.5 L of methanol solvent, add 20 mmol of Zn(NO3)2·6H2O and 1 mmol of CuSO4·5H2O into the methanol, and stir ultrasonically for 20 min to obtain a clear Cu / Zn solution; A2, take 0.5L of methanol solvent, add 14g of 2-methylimidazole to the methanol, and stir ultrasonically for 20min to obtain a 2-methylimidazole-methanol solution; A3. Pour the Cu / Zn solution into the 2-methylimidazole-methanol solution in a volume ratio of 1:1, and stir ultrasonically for 4 hours to obtain a blue mixed solution. Centrifuge the mixed solution to collect the solid component, and then wash the solid component three times with methanol. Dry the washed solid component at a constant temperature of 40°C to constant weight to obtain an adsorbent, which is a ZIF-8 (zeolite imidazolate framework-8) material loaded with Cu.

[0028] Example 2

[0029] Preparation of adsorbent: A1. Take 0.5 L of methanol solvent, add 20 mmol of Zn(NO3)2·6H2O and 1 mmol of CuSO4·5H2O into the methanol, and stir ultrasonically for 40 min to obtain a clear Cu / Zn solution; A2, take 0.5L of methanol solvent, add 14.5g of 2-methylimidazole to the methanol, and stir ultrasonically for 40min to obtain a 2-methylimidazole-methanol solution; A3. Pour the Cu / Zn solution into the 2-methylimidazole-methanol solution in a volume ratio of 1:1, and stir ultrasonically for 5 hours to obtain a blue mixed solution. Centrifuge the mixed solution to collect the solid component, and then wash the solid component three times with methanol. Dry the washed solid component at a constant temperature of 50°C to constant weight to obtain an adsorbent, which is a ZIF-8 (zeolite imidazolate framework-8) material loaded with Cu.

[0030] Example 3

[0031] Preparation of adsorbent: A1. Take 0.5 L of methanol solvent, add 20 mmol of Zn(NO3)2·6H2O and 1 mmol of CuSO4·5H2O into the methanol, and stir ultrasonically for 50 min to obtain a clear Cu / Zn solution; A2, take 0.5L of methanol solvent, add 15g of 2-methylimidazole to the methanol, and stir ultrasonically for 50min to obtain a 2-methylimidazole-methanol solution; A3. Pour the Cu / Zn solution into the 2-methylimidazole-methanol solution in a volume ratio of 1:1, and stir ultrasonically for 5 hours to obtain a blue mixed solution. Centrifuge the mixed solution to collect the solid component, and then wash the solid component three times with methanol. Dry the washed solid component at a constant temperature of 50°C to constant weight to obtain an adsorbent, which is a ZIF-8 (zeolite imidazolate framework-8) material loaded with Cu.

[0032] Example 4

[0033] Preparation of transdermal dosage form: Add methanol solvent to the reaction container, and then stir and add piperine and activated carbon-supported palladium catalyst (palladium content is 10%), wherein the amount ratio of methanol, piperine and activated carbon-supported palladium catalyst is 400mL:50g:2.5g. After the addition is completed, fill the reaction container with nitrogen to replace the air inside the reaction container, and then fill it with hydrogen to replace the nitrogen inside the reaction container. Repeat the hydrogen replacement of the gas in the reaction container three times, and fill the reaction container with hydrogen to 2.0MPa for the last time. After completion, the reaction container is heated to 115°C. , react at a constant temperature and stirring for 2 hours. After the reaction is completed, cool naturally to room temperature to obtain a product, filter the product to recover the activated carbon-supported palladium catalyst, collect the filtrate, and then add 4wt% (4% of the mass of the filtrate) of the adsorbent prepared in Example 1 to the filtrate with stirring, stir at room temperature for 20 minutes, and then filter to remove the adsorbent to obtain a decontaminated product. The decontaminated product is then subjected to reduced pressure distillation to remove the solvent methanol, and the solid component is collected. The solid component is then washed three times with pure water, filtered, and the solid component is then dried to constant weight at a constant temperature of 40°C to obtain a transdermal agent.

[0034] Example 5

[0035] Preparation of transdermal dosage form: Add solvent methanol to the reaction container, and then stir and add piperine and activated carbon-supported palladium catalyst (palladium content is 10%), wherein the amount ratio of methanol, piperine and activated carbon-supported palladium catalyst is 400mL:50g:2.8g. After the addition is completed, fill the reaction container with nitrogen to replace the air inside the reaction container, and then fill it with hydrogen to replace the nitrogen inside the reaction container. Repeat the hydrogen replacement of the gas in the reaction container three times, and fill the reaction container with hydrogen to 2.2MPa for the last time. After completion, the reaction container is heated to 120°C. , react at a constant temperature and stirring for 4 hours. After the reaction is completed, cool naturally to room temperature to obtain a product, filter the product to recover the activated carbon-supported palladium catalyst, collect the filtrate, and then add 8wt% (8% of the mass of the filtrate) of the adsorbent prepared in Example 2 to the filtrate with stirring, stir at room temperature for 30 minutes, and then filter to remove the adsorbent to obtain a decontaminated product. The decontaminated product is then subjected to reduced pressure distillation to remove the solvent methanol, and the solid component is collected. The solid component is washed three times with pure water, filtered, and the solid component is dried to constant weight at a constant temperature of 45°C to obtain a transdermal agent.

[0036] Example 6

[0037] Preparation of transdermal dosage form: Add methanol solvent to the reaction container, and then stir and add piperine and activated carbon-supported palladium catalyst (palladium content is 10%), wherein the amount ratio of methanol, piperine and activated carbon-supported palladium catalyst is 400mL:50g:3.0g. After the addition is completed, nitrogen is filled into the reaction container to replace the air inside the reaction container, and then hydrogen is filled into the reaction container to replace the nitrogen inside the reaction container. Repeat the hydrogen replacement of the gas in the reaction container three times, and hydrogen is filled into the reaction container for the last time to 2.2MPa. After completion, the reaction container is heated to 125°C again. The reaction was stirred at a constant temperature for 4 hours. After the reaction was completed, the mixture was naturally cooled to room temperature to obtain a product. The product was filtered to recover the activated carbon-supported palladium catalyst, the filtrate was collected, and 10 wt % (10% of the mass of the filtrate) of the adsorbent prepared in Example 3 was added to the filtrate with stirring. The mixture was stirred at room temperature for 30 minutes, and the adsorbent was removed by filtration to obtain a decontaminated product. The decontaminated product was then subjected to reduced pressure distillation to remove the solvent methanol, the solid component was collected, and the solid component was washed three times with pure water, filtered, and the solid component was dried to constant weight at a constant temperature of 50° C. to obtain a transdermal agent.

[0038] Comparative Example 1 Comparative Example 1 is the control group of Example 5, and the adsorbent prepared in Example 2 in Example 5 is removed by adsorption purification process, and the remaining raw materials, raw material amounts and preparation methods are consistent with those in Example 5. Specifically, the process of preparing the transdermal agent in Comparative Example 1 is as follows: Add solvent methanol to the reaction container, and then stir and add piperine and activated carbon-supported palladium catalyst (palladium content is 10%) thereto, wherein the amount ratio of methanol, piperine and activated carbon-supported palladium catalyst is 400mL:50g:2.8g. After the addition is completed, nitrogen is filled into the reaction container to replace the air inside the reaction container, and then hydrogen is filled into the reaction container to replace the nitrogen inside the reaction container. The hydrogen replacement of the gas in the reaction container is repeated three times, and hydrogen is filled into the reaction container for the last time to 2.2MPa. After completion, the reaction container is heated to 120°C again, and the reaction is stirred at a constant temperature for 4h. After the reaction is completed, it is naturally cooled to room temperature to obtain a product, and the product is filtered to recover the activated carbon-supported palladium catalyst, and the filtrate is collected. The filtrate is then subjected to reduced pressure distillation to remove the solvent methanol, and the solid component is collected. The solid component is washed three times with pure water, filtered, and the solid component is placed at a constant temperature of 45°C and dried to constant weight to obtain a transdermal agent.

[0039] Example 7

[0040] A medicine for removing birthmarks is prepared by the following steps: S1. Raw material selection: remove insect-eaten, rat-bitten, moldy, deteriorated, fake and inferior products, use medicinal materials without mold or deterioration, wash the medicinal materials repeatedly with clean water and dry them; S2, crushing medicinal materials: crush the medicinal materials and pass them through a 120-mesh sieve, then mix them to obtain a composite powder for later use, wherein the composite powder includes the following raw materials in parts by weight: 20 parts of Angelica dahurica, 20 parts of Radix Bletillae, 20 parts of Atractylodes macrocephalae, 20 parts of Poria cocos, 20 parts of Radix Astragali, 10 parts of Bombyx batryticatus, 10 parts of Bletilla striata, 10 parts of Leonurus japonicus, 1 part of Asarum, 1 part of Radix Aconiti Lateralis, 1 part of Pearl Powder, 1 part of White Clove, 10 parts of Radix Bupleuri, 12 parts of Radix Angelicae Sinensis 15 parts, 15 parts of red peony root, 12 parts of cyperus, 15 parts of salvia miltiorrhiza, 15 parts of safflower, 15 parts of rose, 20 parts of codonopsis, 15 parts of raw rehmannia, 15 parts of jujube, 6 parts of liquorice, 10 parts of chuanxiong, 10 parts of costusroot, 15 parts of prepared rehmannia, 15 parts of wolfberry, 15 parts of dodder seed, 12 parts of glossy privet, 15 parts of eclipta, 15 parts of processed radix polygoni multiflori, 10 parts of cornus officinalis, 12 parts of yam, 6 parts of cassia twig and 10 parts of Morinda officinalis; S3. Preparation of matrix: 50 parts (by mass) of honey are placed in a ceramic container, heated to 115°C with high heat (heating rate of 15°C / min), then switched to low heat (heating rate of 2°C / min) and continued to heat to 118°C, and heated at a constant temperature for 20 seconds. At this time, the honey is light red in color, and the surface is boiling with uniform and shiny bubbles. Take a small amount and cool it to 40°C. Rub it with your hands. It is sticky, but no thin white silk appears when the two fingers are separated. After the constant temperature heating is completed, continue to heat at 100°C. Heat to 122℃ with a slow fire (heating rate of 2℃ / min). At this time, the honey is reddish brown, with reddish brown bubbles boiling on the surface and strong viscosity. Take a small amount and cool it to 40℃ and rub it with your hands. Rub it with two fingers to form white filaments. Drop it into water and it will form beads without falling apart. Then add 6 parts (mass parts) of maltose and 15 parts (mass parts) of beeswax to it, stir it at a constant temperature until the beeswax melts, and then stir it at a constant temperature for 2 minutes to obtain the matrix. Pour the matrix into a stainless steel container while it is hot and set aside. S4, and plaster preparation: when the temperature of the matrix in the stainless steel container is naturally cooled to 60°C, a paste is formed, 50 parts (mass parts) of composite powder are added to the paste, and the paste is stirred until the temperature of the paste drops to 40°C, and then 2 parts (mass parts) of the transdermal agent prepared in Example 4 and 1 part (mass part) of salt are added thereto with stirring, and the stirring and paste are continued for 20 minutes to obtain a paste-like drug for removing birthmarks, and then the paste-like drug for removing birthmarks is made into long strips and cut into small pieces of 2 cm long, placed in a plastic bag, and left to stand at room temperature for 24 hours to obtain a plaster block; S5. Rolling molding: Press the plaster block into a cake shape to obtain a plaster sheet, and use a mold to press the plaster sheet onto the surface of the non-woven plaster patch lining layer to form a birthmark removal plaster patch.

[0041] Example 8

[0042] A medicine for removing birthmarks is prepared by the following steps: S1. Raw material selection: remove insect-eaten, rat-bitten, moldy, deteriorated, fake and inferior products, use medicinal materials without mold or deterioration, wash the medicinal materials repeatedly with clean water and dry them; S2, crushing medicinal materials: crush the medicinal materials and pass them through a 120-mesh sieve, then mix them to obtain a composite powder for later use, wherein the composite powder includes the following raw materials in parts by weight: 20 parts of Angelica dahurica, 20 parts of Radix Bletillae, 20 parts of Atractylodes macrocephalae, 20 parts of Poria cocos, 20 parts of Radix Astragali, 10 parts of Bombyx batryticatus, 10 parts of Bletilla striata, 10 parts of Leonurus japonicus, 1 part of Asarum, 1 part of Radix Aconiti Lateralis, 1 part of Pearl Powder, 1 part of White Clove, 10 parts of Radix Bupleuri, 12 parts of Radix Angelicae Sinensis 15 parts, 15 parts of red peony root, 12 parts of cyperus, 15 parts of salvia miltiorrhiza, 15 parts of safflower, 15 parts of rose, 20 parts of codonopsis, 15 parts of raw rehmannia, 15 parts of jujube, 6 parts of liquorice, 10 parts of chuanxiong, 10 parts of costusroot, 15 parts of prepared rehmannia, 15 parts of wolfberry, 15 parts of dodder seed, 12 parts of glossy privet, 15 parts of eclipta, 15 parts of processed radix polygoni multiflori, 10 parts of cornus officinalis, 12 parts of yam, 6 parts of cassia twig and 10 parts of Morinda officinalis; S3. Preparation of matrix: 50 parts (by mass) of honey are placed in a ceramic container, heated to 110°C with high heat (heating rate of 12°C / min), then switched to low heat (heating rate of 1°C / min) and continued to heat to 118°C, and heated at a constant temperature for 40 seconds. At this time, the honey is light red in color, and the surface is boiling with uniform and shiny bubbles. Take a small amount and cool it to 40°C. Rub it with your hands. It is sticky, but no thin white silk appears when the two fingers are separated. After the constant temperature heating is completed, continue to heat at 100°C. Heat to 120℃ with a slow fire (heating rate of 1℃ / min). At this time, the honey is reddish brown, with reddish brown bubbles boiling on the surface and strong viscosity. Take a small amount and cool it to 40℃ and rub it with your hands. Rub it with two fingers to form white filaments. Drop it into water and it will form beads without falling apart. Then add 7 parts (mass parts) of maltose and 15 parts (mass parts) of beeswax to it, stir it at a constant temperature until the beeswax melts, and then stir it at a constant temperature for 5 minutes to obtain the matrix. Pour the matrix into a stainless steel container while it is hot and set aside. S4, and plaster preparation: when the temperature of the matrix in the stainless steel container is naturally cooled to 70°C, a paste is formed, 50 parts (mass parts) of composite powder are added to the paste, and the paste is stirred until the temperature of the paste drops to 45°C, and then 2 parts (mass parts) of the transdermal agent prepared in Example 5 and 1 part (mass part) of salt are added thereto with stirring, and the stirring and paste are continued for 50 minutes to obtain a paste of the birthmark removal medicine, and then the paste of the birthmark removal medicine is made into a long strip and cut into small pieces of 3 cm long, placed in a plastic bag, and left to stand at room temperature for 24 hours to obtain a plaster block; S5. Rolling molding: Press the plaster block into a cake shape to obtain a plaster sheet, and use a mold to press the plaster sheet onto the surface of the non-woven plaster patch lining layer to form a birthmark removal plaster patch.

[0043] Example 9

[0044] A medicine for removing birthmarks is prepared by the following steps: S1. Raw material selection: remove insect-eaten, rat-bitten, moldy, deteriorated, fake and inferior products, use medicinal materials without mold or deterioration, wash the medicinal materials repeatedly with clean water and dry them; S2, crushing medicinal materials: crush the medicinal materials and pass them through a 120-mesh sieve, then mix them to obtain a composite powder for later use, wherein the composite powder includes the following raw materials in parts by weight: 20 parts of Angelica dahurica, 20 parts of Radix Bletillae, 20 parts of Atractylodes macrocephalae, 20 parts of Poria cocos, 20 parts of Radix Astragali, 10 parts of Bombyx batryticatus, 10 parts of Bletilla striata, 10 parts of Leonurus japonicus, 1 part of Asarum, 1 part of Radix Aconiti Lateralis, 1 part of Pearl Powder, 1 part of White Clove, 10 parts of Radix Bupleuri, 12 parts of Radix Angelicae Sinensis 15 parts, 15 parts of red peony root, 12 parts of cyperus, 15 parts of salvia miltiorrhiza, 15 parts of safflower, 15 parts of rose, 20 parts of codonopsis, 15 parts of raw rehmannia, 15 parts of jujube, 6 parts of liquorice, 10 parts of chuanxiong, 10 parts of costusroot, 15 parts of prepared rehmannia, 15 parts of wolfberry, 15 parts of dodder seed, 12 parts of glossy privet, 15 parts of eclipta, 15 parts of processed radix polygoni multiflori, 10 parts of cornus officinalis, 12 parts of yam, 6 parts of cassia twig and 10 parts of Morinda officinalis; S3. Preparation of matrix: 50 parts (by mass) of honey are placed in a ceramic container, heated to 105°C with high heat (heating rate of 12°C / min), then switched to low heat (heating rate of 1°C / min) and continued to heat to 116°C, and heated at a constant temperature for 40 seconds. At this time, the honey is light red in color, and the surface is boiling with uniform and shiny bubbles. Take a small amount and cool it to 50°C. Rub it with your hands. It is sticky, but no thin white silk appears when the two fingers are separated. After the constant temperature heating is completed, continue to heat at 100°C. Heat to 119°C over a slow fire (heating rate of 1°C / min). At this time, the honey is reddish brown, with reddish brown bubbles boiling on the surface and strong viscosity. Take a small amount and cool it to 50°C, then rub it with your hands. Rub it with two fingers to form white filaments. Drop it into water and it will form beads without dispersing. Then add 7 parts (mass parts) of maltose and 15 parts (mass parts) of beeswax to it, stir it at a constant temperature until the beeswax melts, and then stir it at a constant temperature for 5 minutes to obtain the matrix. Pour the matrix into a stainless steel container while it is hot and set aside. S4, and plaster preparation: when the temperature of the matrix in the stainless steel container is naturally cooled to 70°C, a paste is formed, 50 parts (mass parts) of composite powder are added to the paste, and the paste is stirred until the temperature of the paste drops to 45°C, and then 2 parts (mass parts) of the transdermal agent prepared in Example 6 and 1 part (mass part) of salt are added thereto with stirring, and the stirring and paste are continued for 50 minutes to obtain a paste of the birthmark removal drug, and then the paste of the birthmark removal drug is made into a long strip and cut into small pieces of 3 cm long, placed in a plastic bag, and left to stand at room temperature for 24 hours to obtain a plaster block; S5. Rolling molding: Press the plaster block into a cake shape to obtain a plaster sheet, and use a mold to press the plaster sheet onto the surface of the non-woven plaster patch lining layer to form a birthmark removal plaster patch.

[0045] Comparative Example 2 Comparative Example 2 is the control group of Example 8, and 2 parts (parts by mass) of the transdermal agent prepared by Raw Material Example 5 in Example 8 are replaced by 2 parts (parts by mass) of the transdermal agent prepared by Comparative Example 1, and the remaining raw materials, raw material amounts and preparation methods are kept consistent with those in Example 8, and finally a paste-like drug for removing birthmarks is obtained, and then the paste-like drug for removing birthmarks is made into long strips and cut into small pieces of 3 cm long, placed in a plastic bag, and allowed to stand at room temperature for 24 hours to obtain a plaster block, and the plaster block is pressed into a cake shape to obtain a plaster sheet, and the plaster sheet is pressed onto the surface of the non-woven plaster lining cloth layer with a mold to form a plaster patch for removing birthmarks.

[0046] The ointment-like birthmark removal drugs prepared in Examples 7 to 9 and Comparative Example 2 were tested for efficacy respectively. The efficacy test process is as follows, and the test results are shown in Table 1: 1. Allergy test: patients from a certain hospital, excluding those aged 16 to 55 years old, pregnant or lactating patients, patients with severe endocrine diseases or other organic diseases, patients with a history of drug or other allergies, and those who have used hormone drugs or laser treatment in the past 3 months; because the test adopts a direct skin contact test, and the plaster contains highly irritating Chinese herbal ingredients, such as asarum and white aconite, in order to avoid severe allergic reactions in the test, an allergy test is conducted before formal enrollment. The plaster is applied to one side of the neck and removed after 24 hours. According to the "Diagnostic Standards and Treatment Principles for Cosmetic Skin Diseases", the classification of adverse reactions in human patch tests is formulated, as shown in Table 1. Any score greater than 0 is considered to be positive for the allergy test, so it cannot participate in the test. After the initial screening, a total of 100 qualified volunteers were determined, and the skin automatic analyzer collected the original skin data.

[0047] Table 1 Classification of adverse reactions in human patch tests ; 2. Clinical data: The results of the previous allergy test indicated that only one case of grade 1 skin adverse reaction occurred due to the low dosage of highly irritating Chinese medicines such as white aconite and asarum in the formula. The average age of the 100 patients was 27 years old; the course of disease was 1 to 4 years, with an average of 1.5 years. 35 patients had a history of marriage and childbearing, and 65 were unmarried.

[0048] 3. Diagnostic criteria: light red to dark red patches with clear boundaries, no inflammation or scaling, no obvious subjective symptoms, no obvious endocrine diseases, and exclusion of pigmentation caused by other diseases.

[0049] 4. Treatment method: Apply the plaster prepared by the preparation method of the birthmark removal drug of the present invention to the birthmark once every 5 days, and determine the efficacy after 3 courses of treatment. During the treatment, the patient should avoid spicy and greasy food, eat more fruits and vegetables, avoid sunlight, and avoid using cosmetics.

[0050] 5. Efficacy observation: Observe the color and area of ​​the patient's birthmark and score it.

[0051] Birthmark area score: 0 means no skin lesions; 1 means birthmark area < 2 cm 2 ; 2 is the birthmark area 2~4cm 2 ; 3 birthmark area >4cm 2 .

[0052] Birthmark color scoring: 0 is normal skin color; 1 is light red; 2 is red; 3 is dark red.

[0053] Total score = area score + color score.

[0054] Decline index = (total score before treatment - total score after treatment) / total score before treatment.

[0055] Efficacy criteria: Basically cured: the birthmark area disappears by more than 90% as seen by the naked eye, the color basically disappears, and the reduction index calculated by the scoring method after treatment is ≥0.8; Markedly effective: The birthmark area disappears by more than 60% with naked eyes, the color becomes significantly lighter, and the reduction index calculated by scoring method after treatment is ≥0.5; Improvement: The birthmark area disappears by more than 30% and the color becomes lighter when viewed with the naked eye. The reduction index calculated by the scoring method after treatment is ≥0.3; Ineffective: The birthmark area disappears by less than 30% as seen by the naked eye, the color change is not obvious, and the decline index calculated by the scoring method after treatment is less than 0.

[0056] The statistical method used was rank sum test or chi-square test, and SPSS analysis software was used.

[0057] The overall therapeutic effect of patients after 3 courses of treatment was: 35 cases were basically cured, 39 cases were significantly effective, 15 cases were improved, and 11 cases were ineffective. The total effective rate was 89% and the basic cure rate was 35%.

[0058] Table 1 Overall efficacy ; It can be seen from Table 1 that the ointment-like birthmark-removing drugs prepared in Examples 7 to 9 of the present invention can significantly reduce melanocyte proliferation and remove birthmarks. At the same time, the transdermal agent prepared by the present invention has a significant promoting effect on the efficacy of birthmark removal.

[0059] It should be noted that, in this article, terms such as "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or equipment that includes a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or equipment.

[0060] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A medicine for removing birthmarks, characterized in that: Prepared by the following steps: S1, crushing the medicinal materials and passing them through a 120-mesh sieve, and then mixing them to obtain a composite medicinal powder; S2. Place honey in a ceramic container, heat it to 105-115° C. over high heat, then switch to low heat and continue heating to 116-118° C., heat at a constant temperature for 20-40 seconds, then continue heating at a low heat to 119-122° C., add maltose and beeswax, stir at a constant temperature until the beeswax melts, and stir at a constant temperature for 2-5 minutes to obtain a matrix, and pour the matrix into a stainless steel container while it is hot; S3. When the temperature of the matrix in the stainless steel container is naturally cooled to 60-70°C, add the composite powder thereinto, stir until the temperature drops to 40-45°C, then add the transdermal agent and salt thereinto, and continue stirring for 20-50 minutes to obtain the birthmark removing drug.

2. A drug for removing birthmarks according to claim 1, characterized in that: The mass ratio of the honey, maltose, beeswax, compound medicine powder, transdermal agent and salt is 50:6-7:15:50:2:

1.

3. A medicine for removing birthmarks according to claim 1, characterized in that: The transdermal preparation is prepared by the following steps: Methanol is added to a reaction container, and piperine and activated carbon-supported palladium catalyst are then added thereto with stirring. After the addition is completed, nitrogen is filled into the reaction container to replace the air inside the reaction container, and hydrogen is then filled into the reaction container to replace the nitrogen inside the reaction container. The hydrogen replacement of the gas in the reaction container is repeated three times. The reaction container is filled with hydrogen to 2.0-2.2 MPa for the last time. After completion, the reaction container is heated to 115-125° C. again, and stirred at a constant temperature for reaction for 2-4 hours. After completion of the reaction, the reaction container is naturally cooled to room temperature to obtain a product, and the product is filtered to recover the activated carbon-supported palladium catalyst, and the filtrate is collected. An adsorbent is then added to the filtrate with stirring, and the mixture is stirred at room temperature for 20-30 minutes, and the adsorbent is removed by filtration to obtain an impurity-removed product. The impurity-removed product is then subjected to reduced pressure distillation to remove the solvent methanol, and a solid component is collected. The solid component is then washed with pure water for three times, filtered, and the solid component is dried to a constant weight under a constant temperature of 40-50° C. to obtain a transdermal agent.

4. A drug for removing birthmarks according to claim 3, characterized in that: The palladium content of the activated carbon-supported palladium catalyst is 10%; the dosage ratio of the methanol, piperine and the activated carbon-supported palladium catalyst is 400mL:50g:2.5-3.0g; and the dosage of the adsorbent is 4%-10% of the mass of the filtrate.

5. The drug for removing birthmarks according to claim 3, characterized in that: The adsorbent is prepared by the following steps: A1. Take methanol as solvent, add Zn(NO3)2·6H2O and CuSO4·5H2O into it, and stir ultrasonically for 20-50 min to obtain a clear Cu / Zn solution; A2, take the solvent methanol, add 2-methylimidazole thereto, and stir ultrasonically for 20 to 50 minutes to obtain a 2-methylimidazole-methanol solution; A3. Pour the Cu / Zn solution into the 2-methylimidazole-methanol solution and stir ultrasonically for 4 to 5 hours to obtain a blue mixed solution. Centrifuge the mixed solution to collect the solid component, wash the solid component three times with methanol, and dry the washed solid component at a constant temperature of 40 to 50° C. to constant weight to obtain an adsorbent.

6. A drug for removing birthmarks according to claim 5, characterized in that: The usage ratio of methanol, Zn(NO3)2·6H2O and CuSO4·5H2O in A1 is 0.5L:20mmol:1mmol; the usage ratio of methanol and 2-methylimidazole in A2 is 0.5L:14-15g; the volume usage ratio of Cu / Zn solution and 2-methylimidazole-methanol solution in A3 is 1:

1.

7. The drug for removing birthmarks according to claim 1, characterized in that: The composite powder comprises the following raw materials in parts by weight: 20 parts of angelica dahurica, 20 parts of white peony root, 20 parts of atractylodes macrocephala, 20 parts of white tuckahoe, 20 parts of astragalus, 10 parts of bombyx batryticatus, 10 parts of bletilla striata, 10 parts of motherwort, 1 part of asarum, 1 part of white aconite root, 1 part of pearl powder and 1 part of white lilac.

8. The drug for removing birthmarks according to claim 7, characterized in that: The composite medicinal powder also includes the following raw materials in parts by weight: 10 parts of bupleurum, 12 parts of angelica, 15 parts of red peony root, 12 parts of cyperus, 15 parts of salvia miltiorrhiza, 15 parts of safflower, and 15 parts of rose.

9. The drug for removing birthmarks according to claim 8, characterized in that: The composite medicine powder also includes the following raw materials in parts by weight: 20 parts of Codonopsis pilosula, 15 parts of Rehmannia root, 15 parts of jujube, 6 parts of Licorice root, 10 parts of Chuanxiong and 10 parts of Aucklandia root.

10. The drug for removing birthmarks according to claim 9, characterized in that: The composite powder also includes the following raw materials in parts by weight: 15 parts of Rehmannia root, 15 parts of Lycium barbarum, 15 parts of Cuscuta seed, 12 parts of Ligustrum lucidum fruit, 15 parts of Eclipta prostrata, 15 parts of Polygonum multiflorum processed, 10 parts of Cornus officinalis, and 12 parts of Dioscorea opposita.