Traditional Chinese medicine composition and patch for treating tourette syndrome of children

Abstract

The invention relates to a traditional Chinese medicine composition and patch for treating tourette syndrome of children, and belongs to the technical field of traditional Chinese medicine compositions.The traditional Chinese medicine composition is prepared from calcined oyster shell, semen boitae, radix bupleuri, rhizoma gastrodiae, radix paeoniae alba, rhizoma curcumae longae, periostracum cicada, honey-fried licorice root, rhizoma zingiberis, szechwan chinaberry fruit, rhizoma coptidis, fructus evodiae, uncaria and the like. The preparation method of the patch provided by the invention comprises the following steps: mixing radix bupleuri, uncaria rhynchophylla and the like, and performing alcohol extraction to obtain an alcohol extraction extract; performing water extraction on platycladi seeds, gastrodia elata and the like to obtain water extract; mixing the calcined oyster shell powder, the alcohol extract, the water extract and the hydrogel matrix to obtain a medicine carrying layer; the medicine carrying layer and the permeation enhancing layer are attached, and the patch is obtained after plastic packaging. The composition disclosed by the invention is reasonable in compatibility, has a good treatment effect on the tourette syndrome of children, and is stable in curative effect and good in transdermal absorption efficiency.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese medicine compositions, and particularly relates to a Chinese medicine composition and a patch for treating tics in children. Background Art

[0002] Attention Deficit Hyperactivity Disorder (ADHD) and Tourette Syndrome (TS) are common neurodevelopmental disorders in children, which seriously affect their learning, social interaction and quality of life. ADHD is mainly manifested by inattention, hyperactivity and impulsive behavior, with a global incidence of about 5%-7%; Tourette Syndrome is characterized by motor tics (such as blinking, shrugging) and vocal tics (such as clearing the throat, screaming), with an incidence of about 0.3%-1%. The causes of these two diseases are complex, involving genetic, environmental, neurobiological and psychosocial factors. In terms of genetic factors, mutations in genes related to neurotransmitters such as dopamine and 5-hydroxytryptamine are closely related to the onset of the disease; in terms of environmental factors, smoking, drinking, infection during pregnancy, and environmental toxins such as lead exposure and food additives may increase the risk of disease; in terms of neurobiological factors, children with ADHD have abnormal functions in the prefrontal cortex, striatum and other brain regions, and children with Tourette Syndrome have an imbalance in the dopaminergic system of the basal ganglia; in terms of psychosocial factors, tense family relationships and improper education methods may aggravate symptoms.

[0003] Existing therapeutic drugs mainly include chemical drugs and traditional Chinese medicine compound prescriptions. Among chemical drugs, central nervous system stimulants (such as methylphenidate) and non-stimulants (such as atomoxetine) are commonly used for ADHD, dopamine receptor antagonists (such as haloperidol) and α2 adrenergic agonists (such as clonidine) are commonly used for tics; among traditional Chinese medicine compound prescriptions, Anshen Dingzhi Pills, Chaihu Jia Longgu Muli Decoction, etc. are commonly used for ADHD, and Zhengan Xifeng Decoction, Tianma Gou Teng Yin, etc. are commonly used for tics. However, these treatment methods have obvious defects. Long-term use of chemical drugs is prone to side effects (such as insomnia, loss of appetite, mood swings) and addiction, and some children have limited efficacy and are prone to relapse after discontinuation of medication; although traditional Chinese medicine treatment has few side effects, the traditional decoction has a poor taste, the decoction process is cumbersome, and children have low compliance, making it difficult to adhere to long-term treatment. In addition, the existing transdermal patches for the treatment of childhood tics have problems such as poor drug permeability, poor adhesion, and insufficient comfort, which limits their clinical application. The drugs used to treat tics in the prior art have poor therapeutic effects, unstable therapeutic effects, and poor transdermal absorption efficiency. Summary of the invention

[0004] The invention provides a Chinese medicine composition and a patch for treating tics in children, so as to solve the technical problems that the drugs or patches for treating tics in the prior art have poor therapeutic effects, unstable therapeutic effects and poor transdermal absorption efficiency.

[0005] To achieve the above-mentioned invention object, the present invention provides a traditional Chinese medicine composition for treating childhood tic disorder, and its raw materials include calcined oyster, semen platycladi, bupleurum, gastrodia elata, white peony root, turmeric, cicada slough, roasted licorice root, dried ginger, toosendan fruit, coptis chinensis, evodia rutaecarpa and uncaria rhynchophylla.

[0006] Preferably, the raw materials of the traditional Chinese medicine composition further include polygala tenuifolia, acorus tatarinowii and poria cocos.

[0007] Preferably, its raw materials are calculated by mass parts and include 12 - 15 parts of calcined oyster, 12 - 15 parts of semen platycladi, 3 - 5 parts of bupleurum, 3 - 5 parts of gastrodia elata, 4 - 5 parts of white peony root, 5 - 7 parts of turmeric, 5 - 6 parts of cicada slough, 5 - 7 parts of roasted licorice root, 3 - 4 parts of dried ginger, 3 - 4 parts of toosendan fruit, 3 - 4 parts of coptis chinensis, 2 - 3 parts of evodia rutaecarpa, 6 - 10 parts of uncaria rhynchophylla, 5 - 6 parts of polygala tenuifolia, 4 - 6 parts of acorus tatarinowii and 8 - 10 parts of poria cocos.

[0008] The traditional Chinese medicine composition of the present invention comprehensively regulates the nerves, endocrine and immune systems of children through the synergistic effects of multiple components, multiple targets and multiple pathways, achieving the therapeutic effects of suppressing liver yang and calming endogenous wind, strengthening the spleen and calming the mind, and tonifying the kidney and improving intelligence. The various medicinal materials cooperate with each other, which can not only enhance the curative effect but also reduce side effects, forming the advantage of overall regulation.

[0009] The common use of calcined oyster, gastrodia elata, uncaria rhynchophylla and cicada slough has the effects of suppressing liver yang and calming endogenous wind and regulating neurotransmitters. Calcined oyster subdues yang and tranquilizes the mind, gastrodia elata stops convulsion due to wind, uncaria rhynchophylla clears heat and subdues liver yang, and cicada slough dispels wind-heat. Gastrodin and rhynchophylline can synergistically enhance the inhibitory effect of the GABAergic system and reduce the excessive release of dopamine. The combination of the four can inhibit the abnormal excitement of neurons by regulating the balance of neurotransmitters such as dopamine and GABA, and relieve hyperactivity and tic symptoms.

[0010] Semen platycladi, poria cocos, polygala tenuifolia and acorus tatarinowii have the effects of strengthening the spleen and calming the mind and improving brain function. Semen platycladi nourishes the heart and tranquilizes the mind, poria cocos strengthens the spleen and calms the heart, polygala tenuifolia soothes the nerves and improves intelligence, and acorus tatarinowii resuscitates the mind by opening the orifices. Senegenin and the volatile oil of acorus tatarinowii can synergistically promote the release of acetylcholine and enhance brain function. The combination can improve the attention, memory and cognitive ability by improving the functions of the heart and spleen, enhancing cerebral blood flow and the synthesis of neurotransmitters.

[0011] Bupleurum, toosendan fruit, white peony root and roasted licorice root have the effects of soothing the liver and regulating qi and regulating emotions. Bupleurum soothes the liver and relieves depression, toosendan fruit soothes the liver and promotes qi movement, white peony root nourishes blood and softens the liver, and roasted licorice root coordinates various medicinal ingredients. Saikosaponin and paeoniflorin can synergistically regulate the hypothalamic-pituitary-adrenal axis and relieve stress response. The combination of the four can relieve emotional instability, anxiety and depression by regulating liver qi stagnation and improve the psychological state of children.

[0012] Coptis chinensis, Evodia rutaecarpa, and Curcuma longa have the effects of clearing heat and drying dampness, as well as anti-inflammatory and antioxidant. Coptis chinensis clears heat and dries dampness, Evodia rutaecarpa dispels cold and relieves pain, and Curcuma longa promotes blood circulation and qi movement. Berberine and curcumin in Coptis chinensis can synergistically inhibit the NF-κB pathway and reduce the release of inflammatory factors. When the three are used together, they clear damp-heat in the body, inhibit the inflammatory response, and protect nerve cells from oxidative damage.

[0013] Concha Ostreae (calcined), Poria cocos, and Polygala tenuifolia have the effects of tonifying the kidney and improving intelligence, as well as regulating immunity. Poria polysaccharide and polygala saponin can synergistically enhance the immune regulation function and improve neuroinflammation. When the three are used together, they tonify the kidney and improve intelligence, regulate the immune function, and reduce the damage to the nervous system caused by autoimmune reactions.

[0014] In addition, rhynchophylline and gastrodin in Uncaria rhynchophylla act synergistically to enhance the inhibitory effect of the GABAergic system, significantly improving the sedative and anticonvulsant effects. It complements Concha Ostreae (calcined) and jointly relieves hyperactivity and restlessness caused by hyperactivity of liver yang; it synergistically regulates the hypothalamic-pituitary-adrenal axis with saikosaponin, relieves stress responses, and improves emotional instability. It improves the efficacy stability of the composition or patch and achieves a radical cure for tic disorder.

[0015] The present invention also provides a patch prepared from a traditional Chinese medicine composition. The patch is prepared from the traditional Chinese medicine composition of the present invention, and the preparation method of the patch includes the following steps: S1. Bake Concha Ostreae (calcined) at 300 - 350 °C for 2 - 4 h and then crush it to obtain Concha Ostreae (calcined) powder; S2. Mix Bupleurum chinense, Uncaria rhynchophylla, Acorus tatarinowii, Dry Ginger, and Evodia rutaecarpa, and add them to an ethanol solution according to the ratio of 1 g : 8 - 10 L for reflux extraction 2 - 4 times, each time for 1 hour. After filtration, concentrate under reduced pressure to a relative density of 1.15 - 1.20 (measured at 60 °C) to obtain an ethanol extract paste; S3. Mix Semen Platycladi, Gastrodia elata, Paeonia lactiflora, Curcuma longa, Cicada Slough, Radix Glycyrrhizae Preparata, Toosendan Fruit, Coptis chinensis, Polygala tenuifolia, and Poria cocos and crush them to obtain a water extract powder. Add the water extract powder to distilled water according to the ratio of 1 g : 10 - 15 L for water extraction. After filtration, obtain a water extract solution, and concentrate the water extract solution to a relative density of 1.10 - 1.15 (measured at 60 °C) to obtain a water extract paste; S4. Put Carbomer 940 into purified water to swell for 24 - 26 h, then add glycerol and HPMC, adjust the pH to 6.0 - 6.5, and perform vacuum defoaming to obtain a hydrogel matrix; S5. Heat the acrylate pressure-sensitive adhesive to 60 °C, add tea polyphenols and azone, stir evenly, perform vacuum defoaming, obtain a pressure-sensitive adhesive matrix, coat the pressure-sensitive adhesive matrix on a PET release film, and cure at 80 °C for 30 minutes to obtain a pressure-sensitive adhesive film; S6. Mix the calcined oyster powder, the ethanol extract, the water extract and the hydrogel matrix to obtain a drug-loading layer, and the mass ratio of the total mass of the calcined oyster powder, the ethanol extract and the water extract to the mass of the hydrogel matrix is 1:2 - 3; S7. Precoat a microneedle array (PLGA needles, 200 μm in height, 100 needles / cm² in density) on the pressure-sensitive adhesive film to obtain a penetration-enhancing layer; S8. Bond the drug-loading layer and the penetration-enhancing layer, and then seal them to obtain the patch.

[0016] Preferably, the particle size of the calcined oyster powder in S1 is 100 - 180 microns.

[0017] Preferably, the volume concentration of the ethanol solution in S2 is 75 - 80%.

[0018] Preferably, the particle size of the water extract powder in S3 is less than 60 microns.

[0019] Preferably, the temperature of the water extraction in S3 is 90 - 100 °C, and the time of the water extraction is 3 - 4 h.

[0020] Preferably, the mass ratio of carbomer 940, glycerol, HPMC and purified water in S4 is 2:15:3:80 - 85.

[0021] Preferably, the mass ratio of the acrylate pressure-sensitive adhesive, tea polyphenols and azone in S5 is 55 - 60:2:3. (Industrial-grade tea polyphenols (80 - 95%) can be selected for the preparation of the medicinal patch) In the process of extracting the effective components of traditional Chinese medicine in the present invention, different extraction methods are selected according to different drug characteristics to ensure the dissolution of the effective components. The drug-loading layer of the patch of the present invention contains various traditional Chinese medicine components (such as uncaria rhynchophylla, gastrodia elata, calcined oyster), and through the synergistic effects of multiple pathways such as calming the liver and extinguishing wind, strengthening the spleen and calming the mind, tonifying the kidney and improving intelligence, it comprehensively regulates the nervous, endocrine and immune systems. It significantly improves the core symptoms of tic disorder (such as hyperactivity, tic, inattention). Encapsulating the effective components of traditional Chinese medicine in the hydrogel matrix can ensure the stable release of the drug components. Through the microneedle array and transdermal penetration enhancer (such as azone) of the penetration-enhancing layer, the drug components are directly delivered to the subcutaneous tissue, avoiding the first-pass effect of the liver and gastrointestinal irritation. The microneedle array can penetrate the stratum corneum and form microchannels on the skin surface to promote the transdermal absorption of the drug components. It significantly improves the permeability of the drug components, enhances the transdermal absorption efficiency, enhances the targeting effect, and quickly relieves the symptoms.

[0022] Compared with the prior art, the present invention has the following beneficial effects; The composition of the present invention, including medicinal materials such as Uncaria rhynchophylla, Gastrodia elata, and calcined Oyster, inhibits abnormal neuronal excitation and alleviates hyperactivity and tic symptoms by regulating neurotransmitters such as dopamine and GABA. Supplementary medicinal materials such as Semen Platycladi, Poria cocos, and Polygala tenuifolia improve the functions of the heart and spleen, enhance cerebral blood flow and neurotransmitter synthesis, and improve attention, memory, and cognitive ability. Medicinal materials such as Paeonia lactiflora Pall. and roasted Licorice root tonify the kidney and improve intelligence, regulate immune function, and reduce the damage of autoimmune reactions to the nervous system. The compatibility is reasonable, and it has a good therapeutic effect and stable curative effect on the treatment of childhood tic disorder. It has few side effects and high safety. Using natural Chinese medicine ingredients, it has few side effects and is suitable for long-term use, especially for child patients.

[0023] The patch of the present invention uses a transdermal drug delivery system. The drug components are absorbed through the skin. The microneedle array and transdermal enhancer (such as azone) significantly improve the permeability of the drug components, and the hydrogel matrix ensures the stable release of the drug components, maintains the curative effect, avoids fluctuations in blood drug concentration, and has good transdermal absorption efficiency, and has a significant effect on the treatment of childhood tic disorder. Specific embodiments

[0024] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Based on the described embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention.

[0025] Example 1 This example provides a traditional Chinese medicine composition for treating childhood tic disorder. Its raw materials include 12 parts by mass of calcined Oyster, 12 parts by mass of Semen Platycladi, 3 parts by mass of Bupleurum chinense DC., 3 parts by mass of Gastrodia elata, 4 parts by mass of Paeonia lactiflora Pall., 5 parts by mass of Curcuma longa L., 5 parts by mass of Cryptotympana pustulata Fabricius, 5 parts by mass of roasted Licorice root, 3 parts by mass of dried Ginger, 3 parts by mass of Melia toosendan Sieb. et Zucc., 3 parts by mass of Coptis chinensis Franch., 2 parts by mass of Evodia rutaecarpa (Juss.) Benth., 6 parts by mass of Uncaria rhynchophylla, 5 parts by mass of Polygala tenuifolia Willd., 4 parts by mass of Acorus tatarinowii Schott, and 8 parts by mass of Poria cocos.

[0026] This example also provides a patch prepared from the traditional Chinese medicine composition. The preparation method of the patch includes the following steps: S1. Bake the calcined Oyster at 350 °C for 2 h and then crush it to obtain calcined Oyster powder with a particle size of 100 microns; S2. Mix Bupleurum chinense DC., Uncaria rhynchophylla, Acorus tatarinowii Schott, dried Ginger, and Evodia rutaecarpa (Juss.) Benth., and add them to an ethanol solution with a volume concentration of 75% according to the feeding ratio of 1 g: 8 L and reflux for extraction twice, 1 hour each time. After filtration, concentrate under reduced pressure to a relative density of 1.15 (measured at 60 °C) to obtain an ethanol extract; S3. Mix and crush semen platycladi, gastrodia elata, white peony root, turmeric, cicada slough, roasted licorice root, toosendan fruit, coptis root, polygala root and poria cocos to obtain a water extraction powder with a particle size less than 60 microns. Add the water extraction powder to distilled water at a ratio of 1 g: 10 L for water extraction. The temperature of water extraction is 90 °C and the time is 3 h. After filtration, a water extraction solution is obtained. Concentrate the water extraction solution to a relative density of 1.10 (measured at 60 °C) to obtain a water extraction extract. S4. Put carbomer 940 into purified water and swell it for 24 h, then add glycerol and HPMC, adjust the pH to 6.0, and obtain a hydrogel matrix after vacuum degassing. The mass ratio of carbomer 940, glycerol, HPMC and purified water is 2: 15: 3: 80. S5. Heat the acrylate pressure-sensitive adhesive to 60 °C, add tea polyphenols and azone, stir evenly, and perform vacuum degassing to obtain a pressure-sensitive adhesive matrix. Coat the pressure-sensitive adhesive matrix on a PET release film and cure it at 80 °C for 30 minutes to obtain a pressure-sensitive adhesive film. The mass ratio of acrylate pressure-sensitive adhesive, tea polyphenols and azone is 55: 2: 3. S6. Mix calcined oyster powder, alcohol extraction extract, water extraction extract and hydrogel matrix to obtain a drug-loading layer. The total mass ratio of calcined oyster powder, alcohol extraction extract and water extraction extract to the mass of the hydrogel matrix is 1: 2. S7. Precoat a microneedle array (PLGA needle body, height 200 μm, density 100 needles / cm²) on the pressure-sensitive adhesive film to obtain a penetration-enhancing layer. S8. Bond the drug-loading layer and the penetration-enhancing layer, and obtain the patch after heat-sealing.

[0027] Example 2 This example provides a traditional Chinese medicine composition for treating childhood tic disorder. Its raw materials include 15 parts by mass of calcined oyster, 15 parts by mass of semen platycladi, 5 parts by mass of bupleurum root, 5 parts by mass of gastrodia elata, 5 parts by mass of white peony root, 7 parts by mass of turmeric, 6 parts by mass of cicada slough, 7 parts by mass of roasted licorice root, 4 parts by mass of dried ginger, 4 parts by mass of toosendan fruit, 4 parts by mass of coptis root, 3 parts by mass of evodia rutaecarpa, 10 parts by mass of uncaria rhynchophylla, 6 parts by mass of polygala root, 6 parts by mass of acorus tatarinowii and 10 parts by mass of poria cocos.

[0028] This example also provides a patch prepared from the traditional Chinese medicine composition. The preparation method of the patch includes the following steps: S1. Bake calcined oyster at 350 °C for 4 h and then crush it to obtain calcined oyster powder with a particle size of 180 microns. S2. Mix bupleurum root, uncaria rhynchophylla, acorus tatarinowii, dried ginger and evodia rutaecarpa, and add them to an ethanol solution with a volume concentration of 80% at a ratio of 1 g: 10 L for reflux extraction 4 times, 1 hour each time. After filtration, concentrate it under reduced pressure to a relative density of 1.20 (measured at 60 °C) to obtain an alcohol extraction extract. S3. Mix and crush semen platycladi, gastrodia elata, white peony root, turmeric, cicada slough, roasted licorice root, toosendan fruit, coptis rhizome, polygala root and poria cocos to obtain a water extraction powder with a particle size less than 60 microns. Add the water extraction powder to distilled water according to the feeding ratio of 1 g: 15 L for water extraction. The temperature of water extraction is 100 °C and the time is 4 h. After filtration, a water extraction solution is obtained. Concentrate the water extraction solution to a relative density of 1.15 (measured at 60 °C) to obtain a water extraction extract. S4. Put carbomer 940 into purified water to swell for 26 h, then add glycerol and HPMC, adjust the pH to 6.5, and obtain a hydrogel matrix after vacuum degassing. The mass ratio of carbomer 940, glycerol, HPMC and purified water is 2: 15: 3: 85. S5. Heat the acrylate pressure-sensitive adhesive to 60 °C, add tea polyphenols and azone, stir evenly, and perform vacuum degassing to obtain a pressure-sensitive adhesive matrix. Coating the pressure-sensitive adhesive matrix on a PET release film and curing at 80 °C for 30 minutes to obtain a pressure-sensitive adhesive film. The mass ratio of acrylate pressure-sensitive adhesive, tea polyphenols and azone is 60: 2: 3. S6. Mix calcined oyster powder, alcohol extraction extract, water extraction extract and hydrogel matrix to obtain a drug-loading layer. The total mass ratio of calcined oyster powder, alcohol extraction extract and water extraction extract to the mass of the hydrogel matrix is 1: 3. S7. Precoat a microneedle array (PLGA needle body, height 200 μm, density 100 needles / cm²) on the pressure-sensitive adhesive film to obtain a penetration-enhancing layer. S8. Bond the drug-loading layer and the penetration-enhancing layer, and obtain the patch after plastic sealing.

[0029] Example 3 This example provides a traditional Chinese medicine composition for treating childhood tic disorder. Its raw materials include 13 parts by mass of calcined oyster, 13 parts by mass of semen platycladi, 4 parts by mass of bupleurum root, 4 parts by mass of gastrodia elata, 4.5 parts by mass of white peony root, 6 parts by mass of turmeric, 5.6 parts by mass of cicada slough, 6 parts by mass of roasted licorice root, 3.5 parts by mass of dried ginger, 3.5 parts by mass of toosendan fruit, 3.5 parts by mass of coptis rhizome, 2.5 parts by mass of evodia rutaecarpa, 7 parts by mass of uncaria rhynchophylla, 5.5 parts by mass of polygala root, 5 parts by mass of acorus tatarinowii and 9 parts by mass of poria cocos.

[0030] This example also provides a patch prepared from the traditional Chinese medicine composition. The preparation method of the patch includes the following steps: S1. Bake calcined oyster at 320 °C for 3 h and then crush it to obtain calcined oyster powder with a particle size of 150 microns. S2. Mix bupleurum root, uncaria rhynchophylla, acorus tatarinowii, dried ginger and evodia rutaecarpa, and add them to an ethanol solution with a volume concentration of 78% according to the feeding ratio of 1 g: 9 L for reflux extraction 3 times, 1 hour each time. After filtration, concentrate under reduced pressure to a relative density of 1.17 (measured at 60 °C) to obtain an alcohol extraction extract. S3, mix and crush Platycladus orientalis, Gastrodia elata, White peony root, Curcuma longa, Periostracum cicadae, Radix glycyrrhizae, Toosendan fruit, Coptis chinensis, Polygala tenuifolia and Poria cocos to obtain a water extract powder with a particle size of less than 60 μm, add the water extract powder into distilled water at a feed ratio of 1 g:14 L for water extraction, the water extraction temperature is 95° C., the water extraction time is 3.5 h, and a water extract solution is obtained after filtration, and the water extract solution is concentrated to a relative density of 1.13 (measured at 60° C.) to obtain a water extract; S4, after Carbomer 940 was placed in purified water and swelled for 25 hours, glycerol and HPMC were added, the pH was adjusted to 6.3, and a hydrogel matrix was obtained after vacuum degassing. The mass ratio of Carbomer 940, glycerol, HPMC and purified water was 2:15:3:83; S5, heating the acrylic pressure-sensitive adhesive to 60° C., adding tea polyphenols and azone, stirring evenly, vacuum degassing to obtain a pressure-sensitive adhesive matrix, coating the pressure-sensitive adhesive matrix on a PET release film, and curing at 80° C. for 30 minutes to obtain a pressure-sensitive adhesive film, wherein the mass ratio of the acrylic pressure-sensitive adhesive, tea polyphenols and azone is 58:2:3; S6, mixing the calcined oyster powder, the alcohol extract, the water extract and the hydrogel matrix to obtain a drug-carrying layer, wherein the mass ratio of the total mass of the calcined oyster powder, the alcohol extract and the water extract to the hydrogel matrix is ​​1:2.5; S7, pre-coating a microneedle array (PLGA needle body, 200 μm in height, density 100 needles / cm²) on the pressure-sensitive adhesive film to obtain a permeation-enhancing layer; S8, laminating the drug-carrying layer and the penetration-enhancing layer, and plastic-sealing to obtain the patch.

[0031] Comparative Example 1 This comparative example is the same as Example 1, except that in the Chinese medicine composition in this comparative example, an equal amount of Uncaria rhynchophylla is replaced by Acorus calamus, and an equal amount of Gastrodia elata is replaced by Paeonia lactiflora.

[0032] The size of the patches in Examples 1-3 and Comparative Example 1 was 1 cm*1 cm, the overall thickness was 1 mm, and the thickness of the drug-carrying layer was 0.3 mm.

[0033] 60 male SD rats with a body weight of (200±10) g and an age of 4 weeks were selected. The animals were raised under SPF conditions. The temperature of the breeding environment was (22±2)℃, the relative humidity was 50%-60%, the light was 12h / 12h alternating between light and dark, and sufficient food and water were provided. The animals were from Hunan Slake Jingda Experimental Animal Co., Ltd., and the animal production license number was SYXK (E) 2018-0104. Tiapride hydrochloride (Tiapride, Jiangsu Enhua Pharmaceutical Co., Ltd., National Medicine Standard H32025477, 100 mg / tablet) was prepared with physiological saline to form a suspension containing 2.1 mg / mL of the original drug as the IDPN modeling solution and stored in a refrigerator at 4℃.

[0034] Sixty rats were adaptively fed for 1 week and divided into two parts. One part consisted of 10 rats as the blank control group, and the other part consisted of 50 rats as the model group. The rats in the model group were intraperitoneally injected with the IDPN modeling solution at a dose of 1 mL / (kg·d); the rats in the blank group were intraperitoneally injected with an equal volume of normal saline, both once a day for 7 consecutive days (the stereotyped behavior scores of the mice were recorded starting from the first day of modeling). On the eighth day, the hair on the backs of the rats in the model group was shaved, and the shaved area was 2 cm × 2 cm. The rats in the model group were evenly divided into 5 groups. The first group was fed normally, and the rats in the second, third, fourth, and fifth groups were fed normally while the patches in Example 1, Example 2, Example 3, and Comparative Example 1 were respectively pasted on the shaved areas of the rats. The patches were removed after 6 hours, once a day for 6 consecutive weeks. During this process, the stereotyped behavior scores of the rats in each group at different times were compared using the Kruskal-Wallis test. The comparison results of the stereotyped behavior scores of the rats in each group at different times are shown in Table 1. It can be seen that the twitching behavior of the rats using the patches in Examples 1-3 was improved, and the treatment effect of the twitching behavior in the fifth group was poor, mainly because uncaria rhynchophylla and gastrodia elata were not added, indicating that these two herbs have a good effect on the treatment of tic disorder.

[0035] Table 1 Comparison of stereotyped behavior scores of rats in each group at different times The specific embodiments of the present invention described above do not constitute a limitation on the protection scope of the present invention. Any other corresponding changes and deformations made according to the technical concept of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for treating tics in children, characterized in that: Its raw materials include calcined oyster, cypress seed, bupleurum, gastrodia, white peony root, turmeric, cicada shell, roasted licorice, dried ginger, toosendan fruit, coptis root, evodia rutaecarpa and Uncaria rhynchophylla.

2. A Chinese medicine composition for treating tics in children according to claim 1, characterized in that: The raw materials of the Chinese medicine composition also include Polygala tenuifolia, Acorus calamus and Poria cocos.

3. A Chinese medicine composition for treating tics in children according to claim 2, characterized in that: The raw materials include 12-15 parts of calcined oyster, 12-15 parts of cypress seed, 3-5 parts of bupleurum, 3-5 parts of gastrodia, 4-5 parts of white peony, 5-7 parts of turmeric, 5-6 parts of cicada shell, 5-7 parts of roasted licorice, 3-4 parts of dried ginger, 3-4 parts of toosendan fruit, 3-4 parts of coptis, 2-3 parts of evodia, 6-10 parts of Uncaria rhynchophylla, 5-6 parts of polygala, 4-6 parts of calamus and 8-10 parts of poria.

4. A patch prepared based on the Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The patch is prepared from the Chinese medicine composition, and the preparation method of the patch comprises the following steps: S1, baking the calcined oyster at 300-350°C for 2-4h and then crushing it to obtain calcined oyster powder; S2, mixing Bupleurum, Uncaria rhynchophylla, Acorus calamus, dried ginger and Evodia rutaecarpa in a ratio of 1 g: 8-10 L, adding the mixture to an ethanol solution for reflux extraction 2-4 times, each time for 1 hour, filtering and concentrating under reduced pressure to a relative density of 1.15-1.20, and obtaining an alcohol extract; S3, mixing and crushing cypress seed, gastrodia elata, white peony root, turmeric, cicada slough, licorice root, toosendan fruit, coptis root, polygala tenuifolia and poria to obtain a water extract powder, adding the water extract powder into distilled water at a feed ratio of 1g:10-15L for water extraction, filtering to obtain a water extract solution, concentrating the water extract solution to a relative density of 1.10-1.15 to obtain a water extract; S4, placing Carbomer 940 in purified water to swell for 24-26 hours, then adding glycerol and HPMC, adjusting the pH to 6.0-6.5, and vacuum degassing to obtain a hydrogel matrix; S5, heating the acrylic pressure-sensitive adhesive to 60° C., adding tea polyphenols and azone, stirring evenly, vacuum degassing to obtain a pressure-sensitive adhesive matrix, coating the pressure-sensitive adhesive matrix on a PET release film, and curing to obtain a pressure-sensitive adhesive film; S6, mixing the calcined oyster powder, the alcohol extract, the water extract and the hydrogel matrix to obtain a drug-carrying layer, wherein the mass ratio of the total mass of the calcined oyster powder, the alcohol extract and the water extract to the hydrogel matrix is ​​1:2-3; S7, pre-coating a microneedle array on the pressure-sensitive adhesive film to obtain a permeation-enhancing layer; S8, laminating the drug-carrying layer and the penetration-enhancing layer, and plastic-sealing to obtain the patch.

5. The patch according to claim 4, characterized in that The particle size of the calcined oyster powder in S1 is 100-180 microns.

6. The patch according to claim 4, characterized in that The volume concentration of the ethanol solution in S2 is 75-80%.

7. The patch according to claim 4, characterized in that The particle size of the water-extracted powder in S3 is less than 60 microns.

8. The patch according to claim 4, characterized in that The water extraction temperature in S3 is 90-100° C., and the water extraction time is 3-4 h.

9. The patch according to claim 4, characterized in that The mass ratio of Carbomer 940, glycerol, HPMC and purified water described in S4 is 2:15:3:80-85.

10. The patch according to claim 4, characterized in that The mass ratio of the acrylic pressure-sensitive adhesive, tea polyphenols and azone in S5 is 55-60:2:3.

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