A traditional Chinese medicine composition for treating children's tic disorder, a preparation method and application thereof

Abstract

This invention discloses a traditional Chinese medicine composition, preparation method, and application for treating childhood tic disorders, belonging to the field of traditional Chinese medicine technology. It solves the technical problem that existing traditional Chinese medicine compositions for treating childhood tic disorders are ineffective in cases of phlegm-fire disturbance syndrome. The traditional Chinese medicine composition of this invention, by weight, is made from the following medicinal materials: 6-9 parts of Pinellia ternata, 6-10 parts of Gardenia jasminoides, 3-6 parts of Bambusa textilis, 3-6 parts of Arisaema cum Bile, 6-10 parts of Acorus tatarinowii, 5-12 parts of Curcuma longa, 5-12 parts of Uncaria rhynchophylla, 10-20 parts of pearl powder, 3-9 parts of Angelica dahurica, 6-10 parts of Citrus reticulata peel, 6-12 parts of Poria cocos, 6-12 parts of Atractylodes macrocephala, 6-12 parts of Codonopsis pilosula, and 3-5 parts of Buthus martensii. The preparation method of the traditional Chinese medicine composition for treating childhood tic disorders of this invention includes: extracting the effective components by decoction, the steps of which are as follows: weighing the medicinal materials; adding water and decocting twice, each time for at least 0.5 hours; filtering and combining the decoctions. This invention has the advantage of being effective in treating the phlegm-fire disturbance syndrome of childhood tic disorders.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition, preparation method, and application for treating tic disorders in children. Background Technology

[0002] Tic disorders are a common neuropsychiatric illness that begins in childhood or adolescence. They are characterized by involuntary, repetitive, sudden, rapid, and arrhythmic motor tics and / or vocal tics in one or more parts of the body. Common manifestations include blinking, nose twitching, head tilting, throat clearing, and coprolalia. The etiology is not fully understood, but it is believed to be the result of interactions between genetic factors, organic brain factors, neurobiochemical factors, immune factors, psychological factors, and environmental factors. TD can be accompanied by numerous behavioral and psychological problems, such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), learning disabilities, sleep disorders, mood disorders, and self-harm, seriously harming children's physical and mental health and normal learning and life. It also causes varying degrees of harm to families, schools, and society, thus attracting high attention from parents and pediatricians. Currently, Western medicine commonly uses dopamine receptor blockers such as sulpiride and haloperidol, and norepinephrine-like drugs such as clonidine and guanethidine for treatment. However, these drugs have many adverse reactions, such as weight gain, low blood pressure, and bradycardia. Abrupt discontinuation of the drug can easily lead to rebound phenomena. Therefore, it is particularly important to find safe, reliable and effective treatment methods.

[0003] Tic disorders fall under the categories of "convulsions" and "chronic infantile convulsions" in Traditional Chinese Medicine (TCM). The pathogenesis of this disease is complex, involving many factors such as wind (external and internal wind), phlegm (intangible phlegm), fire (liver fire), blood stasis (due to prolonged illness affecting the collaterals, childbirth injuries, and external injuries), and deficiency (kidney yin deficiency and spleen qi deficiency). Wind and phlegm are most closely related, and internal disturbance of phlegm and fire is also common. Prolonged phlegm stagnation can transform into fire and generate wind; the accumulation of wind, fire, and phlegm disrupts the meridians and affects the internal organs, leading to frequent, recurring, and unpredictable tic symptoms. Years of clinical practice have proven that TCM treatment for tic disorders is effective, significantly reducing or even completely controlling tic symptoms, improving comorbidities, lowering the recurrence rate, and having fewer adverse reactions, demonstrating significant advantages.

[0004] Phlegm-fire disturbance syndrome is a common clinical syndrome of tic disorders. Its main symptoms include involuntary tics of the muscles of the head, face, neck, shoulders, trunk, and limbs, sometimes accompanied by abnormal vocalizations of the mouth, nose, and throat, occasional coprolalia, a preference for rich and sweet foods, dry and bitter mouth, irritability, hot palms and soles, restless sleep, dry stools, scanty and dark yellow urine, and a red tongue with a thin yellow or thin yellow-greasy coating. Currently, the drug formulations used to treat tic disorders of phlegm-fire disturbance syndrome in children are limited, mainly consisting of traditional Chinese medicine decoctions. However, these decoctions suffer from drawbacks such as poor taste, difficulty in administration, difficulty in dosage control, short shelf life, and inconvenience in storage and portability, thus limiting treatment options. Furthermore, there are very few effective and safe traditional Chinese medicine compositions available on the market for treating tic disorders of phlegm-fire disturbance syndrome in children. Therefore, there is an urgent need to develop a traditional Chinese medicine composition, preparation method, and application for treating tic disorders of phlegm-fire disturbance syndrome to overcome these shortcomings. Summary of the Invention

[0005] This invention provides a traditional Chinese medicine composition, preparation method, and application for treating childhood tic disorders, in order to address the technical problem that the efficacy and safety of existing traditional Chinese medicine compositions for treating childhood tic disorders need further improvement in the phlegm-fire disturbance syndrome type.

[0006] The technical solution adopted in this invention is as follows:

[0007] A traditional Chinese medicine composition for treating tic disorders in children, made from the following Chinese medicinal materials in parts by weight:

[0008] Pinellia ternata 6-9 parts, Gardenia jasminoides 6-10 parts, Bambusa textilis 3-6 parts, Arisaema cum Bile 3-6 parts, Acorus tatarinowii 6-10 parts, Curcuma longa 5-12 parts, Uncaria rhynchophylla 5-12 parts, Margarita 10-20 parts, Angelica dahurica 3-9 parts, Citrus reticulata 6-10 parts, Poria cocos 6-12 parts, Atractylodes macrocephala 6-12 parts, Codonopsis pilosula 6-12 parts, Buthus martensii 3-5 parts.

[0009] The principle of the prescription: Pinellia ternata in the prescription dries dampness, resolves phlegm, clears phlegm and calms the mind, while Gardenia jasminoides clears heat, relieves irritability, and eliminates dampness. Together they are the principal herbs. Bamboo shavings, Arisaema cum Bile, and Acorus tatarinowii clear heat and resolve phlegm, calm wind and stop tics; Curcuma longa invigorates blood and qi, clears the heart and relieves depression; Uncaria rhynchophylla clears heat and calms the liver, calms wind and stops convulsions; Mother-of-pearl calms the liver and subdues yang, soothes the mind and stops convulsions. These are the assistant herbs. Angelica dahurica relieves exterior wind and opens the nasal passages to prevent external wind from triggering internal wind; Citrus reticulata regulates qi and harmonizes the middle jiao, dries dampness and resolves phlegm; Poria cocos, Atractylodes macrocephala, and Codonopsis pilosula mildly invigorate the spleen to eliminate phlegm, harmonize the middle jiao and strengthen the earth to prevent the source of phlegm and prevent the accumulation of dampness. These are the adjuvant herbs. Scorpion calms wind and unblocks the meridians, guiding the other herbs directly to the affected area, allowing the various components in the formula to work synergistically. This Chinese herbal combination has therapeutic effects in clearing heat and resolving phlegm, calming wind and stopping tics, relieving exterior wind, invigorating blood and unblocking the meridians, regulating liver qi, strengthening the spleen and harmonizing the middle jiao, and calming the mind and soothing the nerves. It has a positive effect on improving the symptoms and causes of tic disorders in children.

[0010] This invention uses traditional Chinese medicine as raw materials to fully utilize the pharmacological effects of each component:

[0011] Pinellia ternata (processed): pungent, warm. Enters the spleen, stomach, and lung meridians. Dries dampness and resolves phlegm. Used for cough and asthma with excessive phlegm, dizziness and palpitations due to phlegm retention, vertigo due to wind-phlegm, and headache due to phlegm syncope.

[0012] The chemical components of Pinellia ternata include alkaloids, organic acids, volatile oils, flavonoids, steroids, and sugars. Pinellia ternata also has pharmacological effects such as expectorant, antiemetic, anti-inflammatory, antibacterial, and anti-epileptic properties. It can effectively reduce tics caused by infection and improve gastrointestinal symptoms such as vocal cord dysphonia and nausea and vomiting.

[0013] Gardenia: Bitter, cold. Enters the Heart, Lung, and Triple Energizer meridians. Clears heat and relieves irritability, promotes diuresis and eliminates dampness, cools the blood and detoxifies; externally used to reduce swelling and relieve pain. Used for feverish irritability. Also used for damp-heat jaundice, painful urination, hematemesis and epistaxis due to blood heat, red and swollen eyes, and sores caused by fire toxins; externally used to treat sprains and contusions.

[0014] Gardenia contains iridoids, monoterpenoid glycosides, volatile oils, polysaccharides, and various trace elements. It exhibits certain activities in neuroprotection, anti-inflammation, and anti-fatigue. It can effectively improve symptoms such as depression, irritability, poor concentration, memory loss, and fatigue in children with tic disorders.

[0015] Arisaema cum Bile: Bitter, slightly pungent, and cool in nature. It enters the lung, liver, and spleen meridians. It clears heat and resolves phlegm, calms wind and relieves convulsions. It is used for cough with phlegm-heat, thick yellow sputum, stroke with phlegm-induced coma, and epilepsy.

[0016] Arisaema cum Bile contains bile acids, flavonoids, phenols, nucleosides, and sugars. Its pharmacological effects include clearing heat, anti-inflammatory and analgesic, anticonvulsant, and antioxidant properties, which can effectively improve tic symptoms.

[0017] Acorus tatarinowii: pungent, bitter, and warm. It enters the Heart and Stomach meridians. It opens the orifices and resolves phlegm, refreshes the mind and improves intelligence, and transforms dampness and stimulates appetite. It is used for coma, epilepsy, forgetfulness, insomnia, tinnitus, deafness, abdominal distension, loss of appetite, and diarrhea with aphthous stomatitis.

[0018] Sweet flag contains volatile oils, sugars, organic acids, amino acids, and other components. Different chemical components have good medicinal effects on the central nervous system and digestive system, and have anticonvulsant, antidepressant, sedative and hypnotic effects. It can effectively improve the inattention, nightmares, and emotional instability of children with tic disorders.

[0019] Turmeric: pungent, bitter, and cold. It enters the liver, gallbladder, and heart meridians. It invigorates blood circulation, relieves pain, regulates qi, alleviates depression, clears heat from the heart, and cools the blood. It is used for stabbing pain in the chest and hypochondrium, chest pain, amenorrhea, dysmenorrhea, delirium due to febrile disease, epilepsy, and hematemesis due to blood heat.

[0020] Turmeric mainly contains volatile oils, curcumin, polysaccharides, and trace elements. It possesses anti-inflammatory, analgesic, central nervous system depressant, antidepressant, and immunosuppressive effects. In treating tic disorders, it can effectively alleviate symptoms such as irritability and low mood, and by regulating emotions and immune function, it reduces tic symptoms.

[0021] Mother-of-pearl: Salty, cold. Enters the liver and heart meridians. Calms the liver and suppresses yang, soothes the mind, calms fright, and improves vision. Used for liver yang hyperactivity, dizziness, palpitations, insomnia, restlessness, red and pterygium eyes, and blurred vision.

[0022] Mother-of-pearl's chemical composition mainly consists of several major categories of components, including inorganic salts, trace elements, and amino acids. It possesses sedative, hypnotic, calming, immune-regulating, and antibacterial effects. By regulating nervous system function, reducing inflammation levels, and modulating the immune system, it can thus improve tic symptoms.

[0023] Angelica dahurica: pungent, warm. Enters the lung, stomach, and large intestine meridians. Relieves exterior syndromes and dispels cold, dispels wind and relieves pain, clears nasal passages, reduces swelling and drains pus. Used for colds with headache, supraorbital neuralgia, nasal congestion and runny nose, rhinitis, sinusitis, and sores and swelling.

[0024] Angelica dahurica mainly contains coumarins and volatile oils. It has analgesic, anti-inflammatory, antispasmodic, and motor and respiratory center stimulant effects. It helps prevent and alleviate tic symptoms such as nose twitching and throat clearing caused by infection in children with tic disorders.

[0025] Uncaria rhynchophylla: Sweet, cool. Enters the liver and pericardium meridians. Clears heat and calms the liver, extinguishes wind and relieves convulsions. Used for internal liver wind, epilepsy and convulsions, high fever convulsions, colds with convulsions, infantile convulsions, headache and dizziness.

[0026] Uncaria rhynchophylla mainly contains alkaloids, triterpenoids, phenols, sterols, flavonoids, quinones, coumarins, and lignans, which have sedative, anticonvulsant, antidepressant, and antiepileptic effects. It can enhance the resilience and function of the nervous system, protect nerve cells, and reduce tic symptoms.

[0027] Dried tangerine peel: bitter, pungent, and warm. It enters the lung and spleen meridians. It regulates qi and strengthens the spleen, dries dampness and resolves phlegm. It is used for abdominal distension, poor appetite, vomiting and diarrhea, and cough with excessive phlegm.

[0028] Dried tangerine peel contains nearly a hundred components, including flavonoids, alkaloids, triterpenoids, and volatile oils. Its main functions include regulating intestinal motility and homeostasis, relieving spasms, and expectorating phlegm. In treating tic disorders, dried tangerine peel can alleviate gastrointestinal symptoms such as indigestion and abdominal pain.

[0029] Atractylodes macrocephala: Sweet, bitter, and warm. It enters the spleen and stomach meridians. It strengthens the spleen and replenishes qi, dries dampness and promotes urination, and stops sweating. It is used for spleen deficiency with poor appetite, abdominal distension and diarrhea, phlegm retention with dizziness and palpitations, and edema.

[0030] Atractylodes macrocephala contains volatile oils, polysaccharides, amino acids, and other chemical components. It has the effects of regulating immunity, improving gastrointestinal function, regulating intestinal flora, protecting nerves, anti-inflammation, and antibacterial properties. It can improve nausea, vomiting, poor appetite, and low immunity in children with tic disorders to a certain extent.

[0031] Poria cocos: Sweet, bland, and neutral. It enters the heart, lung, spleen, and kidney meridians. It promotes diuresis and eliminates dampness, strengthens the spleen, and calms the mind. It is used for edema with scanty urine, phlegm retention with dizziness and palpitations, spleen deficiency with poor appetite, loose stools and diarrhea, restlessness, palpitations, and insomnia.

[0032] Poria cocos contains a variety of chemical components such as triterpenoids, polysaccharides, sterols, and volatile oils. It has pharmacological effects such as immunomodulation and diuresis, and can regulate the immune status of children with tic disorders, improve immunity, and reduce the recurrence frequency of tic disorders.

[0033] Codonopsis pilosula: Sweet, neutral. It enters the spleen and lung meridians, strengthens the spleen and benefits the lungs, nourishes blood and generates fluids. It is used for spleen and lung qi deficiency, poor appetite and fatigue, cough and wheezing, insufficient qi and blood resulting in a sallow complexion, palpitations and shortness of breath, thirst due to fluid depletion, and internal heat and thirst.

[0034] Codonopsis pilosula contains chemical components such as alkaloids, alkynes, terpenes, flavonoids, and sugars. It has a wide variety of pharmacological effects, mainly affecting the nervous system, immune system, and digestive system. It has protective and anti-inflammatory effects. In the treatment of tic disorders, it can improve children's inattention, memory loss, and gastrointestinal dysfunction.

[0035] Bamboo Sap: Sweet, cold. Enters the Heart and Liver meridians. Clears heat and resolves phlegm, calms the mind and relieves convulsions. Used for infantile convulsions, stroke, epilepsy, delirium due to febrile disease, cough and asthma due to phlegm-heat, and night crying.

[0036] Bamboo shavings mainly contain silicates, inorganic elements, and a small amount of amino acids and other chemical components. They have neuroprotective, expectorant, antipyretic, anti-inflammatory, sedative, and anticonvulsant effects. In the treatment of tic disorders, they can effectively improve symptoms such as irritability, nightmares, and coprolalia in children with tic disorders.

[0037] Scorpion: Pungent, neutral; toxic. Enters the Liver meridian. Calms wind and relieves spasms, unblocks meridians and relieves pain, attacks toxins and dissipates nodules. Used for internal liver wind, spasms and convulsions, infantile convulsions, stroke with slurred speech, hemiplegia, tetanus, stubborn rheumatism, migraine, sores, and scrofula.

[0038] The main components of whole scorpion include proteins, polypeptides, alkaloids, and lipids, which act on the nervous system and possess various pharmacological effects such as anti-inflammatory, antibacterial, analgesic, and anticoagulant properties. It can regulate disordered immune function, alleviate nervous system problems, and relieve tic symptoms caused by inflammation.

[0039] The preferred traditional Chinese medicine composition for treating childhood tic disorders of this invention is made from the following traditional Chinese medicinal materials in parts by weight:

[0040] Pinellia ternata 8g, Gardenia jasminoides 8g, Bambusa textilis 6g, Arisaema cum bile 5g, Acorus tatarinowii 8g, Curcuma longa 8g, Uncaria rhynchophylla 10g, Margarita 18g, Angelica dahurica 9g, Citrus reticulata 9g, Poria cocos 12g, Atractylodes macrocephala 9g, Codonopsis pilosula 12g, Scorpion 3g.

[0041] The present invention provides a preferred traditional Chinese medicine composition for treating tic disorders in children, wherein the preparation of the traditional Chinese medicine composition is any one of decoction, granules, powder, tablets, oral liquid, and capsules.

[0042] A method for preparing a traditional Chinese medicine composition for treating tic disorders in children includes extracting the active ingredients by decoction. The decoction steps are as follows: weigh the required Chinese medicinal materials; add water and decoct twice, each time for at least 0.5 hours; filter and combine the decoctions.

[0043] Further, the decoction is concentrated to a viscous paste, an ethanol solution is added to the viscous paste product for alcohol precipitation, the mixture is allowed to stand, filtered, and concentrated.

[0044] A method for preparing a traditional Chinese medicine composition for treating tic disorders in children includes extracting the active ingredients by ethanol extraction. The steps of ethanol extraction are as follows: adding ethanol solution for reflux extraction, filtering the extract, and then concentrating the extract.

[0045] The present invention provides a preferred method for preparing a traditional Chinese medicine composition for treating tic disorders in children, wherein the concentration of the ethanol solution is 60-70%, and the extraction process is carried out in an ultrasonic manner.

[0046] The present invention provides a preferred method for preparing a traditional Chinese medicine composition for treating tic disorders in children, wherein the extract is concentrated to obtain a concentrate, which is then purified using D101 macroporous resin, and the concentrate has a relative density of 1.10-1.20.

[0047] Furthermore, in order to clean the macroporous resin, it was first eluted with 2 BV of water, and then eluted with 5 BV of 60% ethanol solution. The ethanol eluent was collected and the ethanol was recovered.

[0048] The application of traditional Chinese medicine composition for treating childhood tic disorders in the treatment of tic disorders caused by phlegm-fire disturbance in children.

[0049] In summary, compared with the prior art, the present invention has the following advantages and beneficial effects:

[0050] 1. This invention selects 14 kinds of Chinese medicinal materials for compatibility, and can prepare a variety of preparations as needed to meet the needs of different patients. It has a good effect on treating phlegm-fire disturbance syndrome in children with tic disorders.

[0051] 2. This invention extracts the active ingredients with ethanol and then purifies them with macroporous resin, maximizing the extraction of active ingredients and removing impurities, thereby improving efficacy and reducing side effects caused by impurities, and ensuring high safety. Detailed Implementation

[0052] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the embodiments. The illustrative embodiments and descriptions of this invention are only for explaining this invention and are not intended to limit this invention.

[0053] Example 1

[0054] A traditional Chinese medicine composition for treating tic disorders in children, made from the following Chinese medicinal materials in parts by weight:

[0055] Curcuma longa 6g, Citrus reticulata peel 8g, Pinellia ternata 6g, Arisaema cum bile 5g, Atractylodes macrocephala 6g, Buthus martensii 3g, Gardenia jasminoides 6g, Acorus tatarinowii 6g, Margarita 10g, Bambusa textilis 3g, Angelica dahurica 5g, Codonopsis pilosula 6g, Poria cocos 10g, Uncaria rhynchophylla 5g.

[0056] Example 2

[0057] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0058] Turmeric 8g, Tangerine Peel 10g, Prepared Pinellia 8g, Arisaema cum Bile 6g, Atractylodes macrocephala 6g, Scorpion 3g, Gardenia 8g, Acorus tatarinowii 8g, Mother-of-Pearl 12g, Bambusa textilis 4g, Angelica dahurica 6g, Codonopsis pilosula 8g, Poria cocos 6g, Uncaria rhynchophylla 6g.

[0059] Example 3

[0060] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0061] Turmeric 10g, Tangerine Peel 8g, Prepared Pinellia 9g, Arisaema cum Bile 3g, Atractylodes macrocephala 8g, Scorpion 5g, Gardenia 10g, Acorus tatarinowii 10g, Pearl powder 15g, Bambusa textilis 5g, Angelica dahurica 8g, Codonopsis pilosula 10g, Poria cocos 8g, Uncaria rhynchophylla 8g.

[0062] Example 4

[0063] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0064] Turmeric 8g, Tangerine Peel 9g, Prepared Pinellia 8g, Arisaema cum Bile 5g, Atractylodes macrocephala 9g, Scorpion 3g, Gardenia 8g, Acorus tatarinowii 8g, Mother-of-Pearl 18g, Bambusa textilis 6g, Angelica dahurica 9g, Codonopsis pilosula 12g, Poria cocos 12g, Uncaria rhynchophylla 10g.

[0065] Example 5

[0066] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0067] Turmeric 9g, Tangerine Peel 6g, Prepared Pinellia 8g, Arisaema cum Bile 5g, Atractylodes macrocephala 10g, Scorpion 3g, Gardenia 6g, Acorus tatarinowii 9g, Mother-of-Pearl 20g, Bambusa textilis 5g, Angelica dahurica 8g, Codonopsis pilosula 12g, Poria cocos 10g, Uncaria rhynchophylla 12g

[0068] Example 6

[0069] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0070] Turmeric 6g, Tangerine Peel 8g, Prepared Pinellia 9g, Arisaema cum Bile 6g, Atractylodes macrocephala 12g, Scorpion 3g, Gardenia 10g, Acorus tatarinowii 10g, Pearl powder 15g, Bambusa textilis 3g, Angelica dahurica 6g, Codonopsis pilosula 10g, Poria cocos 12g, Uncaria rhynchophylla 10g.

[0071] Example 7

[0072] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0073] Curcuma longa 6g, Citrus reticulata peel 8g, Pinellia ternata 6g, Arisaema cum bile 5g, Atractylodes macrocephala 7g, Buthus martensii 5g, Gardenia jasminoides 10g, Acorus tatarinowii 9g, Margarita 12g, Bambusa textilis 5g, Angelica dahurica 8g, Codonopsis pilosula 12g, Poria cocos 12g, Uncaria rhynchophylla 6g

[0074] Example 8

[0075] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0076] Turmeric 10g, Tangerine Peel 10g, Prepared Pinellia 9g, Arisaema cum Bile 6g, Atractylodes macrocephala 12g, Scorpion 3g, Gardenia 8g, Acorus tatarinowii 10g, Mother-of-Pearl 20g, Bambusa textilis 6g, Angelica dahurica 9g, Codonopsis pilosula 10g, Poria cocos 10g, Uncaria rhynchophylla 12g

[0077] Example 9

[0078] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0079] Turmeric 10g, Tangerine Peel 6g, Prepared Pinellia 6g, Arisaema cum Bile 3g, Atractylodes Macrocephala 6g, Scorpion 3g, Gardenia 10g, Acorus 10g, Mother-of-Pearl 10g, Bambusa Textilis 4g, Angelica Dahurica 6g, Codonopsis 10g, Poria 10g, Uncaria 6g

[0080] Example 10

[0081] The difference between this embodiment and Embodiment 1 lies in the following medicinal herb components:

[0082] Turmeric 5g, Tangerine Peel 6g, Prepared Pinellia 6g, Arisaema cum Bile 3g, Atractylodes macrocephala 6g, Scorpion 3g, Gardenia 6g, Acorus tatarinowii 6g, Pearl powder 10g, Bambusa textilis 3g, Angelica dahurica 3g, Codonopsis pilosula 6g, Poria cocos 6g, Uncaria rhynchophylla 5g.

[0083] The extraction methods for the effective components of the aforementioned Chinese medicinal materials include the following:

[0084] (1) The above fourteen Chinese medicinal materials are decocted twice with water, each time for 0.5 hours. The decoctions are combined, filtered and concentrated.

[0085] (2) The above fourteen Chinese medicinal materials were extracted twice by reflux with water, each time for 1.5 hours. The decoctions were combined, filtered and concentrated.

[0086] (3) The above fourteen Chinese medicinal materials were extracted by reflux with 8 times the amount of 60% ethanol three times, for 1 hour each time; the extracts were combined, filtered, the ethanol was recovered and concentrated to a thick paste with a relative density of 1.30 to 1.34 (measured at 50℃).

[0087] (4) The above fourteen Chinese medicinal materials were extracted twice with 70% ethanol by ultrasonic extraction, the first time for 1 hour and the second time for 0.5 hours. The extracts were combined, filtered, concentrated, and purified by D101 macroporous resin.

[0088] Regarding the treatment of macroporous resin: first elute with 2 BV of water, then elute with 5 BV of ethanol solution, collect the ethanol eluent, and recover the ethanol.

[0089] (5) The above fourteen Chinese medicinal materials are decocted twice with water, each time for 0.5 hours. The decoctions are combined, filtered, concentrated, and then precipitated with 70% ethanol solution. After standing, the decoctions are filtered and concentrated.

[0090] The above-mentioned concentrated extracts of active ingredients are used to prepare powders, granules, tablets or capsules.

[0091] The above fourteen Chinese medicinal herbs are decocted twice with water, each time for 0.5 hours. The decoctions are then combined to form a soup, which is called Qinghuo Ditan Decoction.

[0092] In the above embodiments, Example 4 was evaluated as a formula with better efficacy. It was prepared into Qinghuo Ditan Decoction using the decoction preparation method. In addition, a concentrated liquid was prepared according to the preparation method of method (4), and then excipients were added to prepare granules, namely Qinghuo Ditan Granules, for later clinical trials.

[0093] Clinical data

[0094] 1. Cases and Clinical Methods

[0095] 1.1 Case Data

[0096] The observed cases were all from the pediatric outpatient department of Chongqing Traditional Chinese Medicine Hospital from August 2022 to August 2023, totaling 92 cases. They were randomly divided into three groups: experimental group 1, experimental group 2, and control group. Experimental group 1 consisted of 31 cases, but one patient dropped out due to non-compliance with the treatment plan after enrollment, leaving 30 cases completed. Experimental group 2 also consisted of 30 cases. The control group consisted of 31 cases, but one patient was excluded due to poor compliance, leaving 30 cases completed. A total of 90 cases were actually completed. There were no statistically significant differences in age, gender, disease duration, and clinical characteristics among the three groups (P>0.05), indicating comparability.

[0097] The case details are shown in Table 1 below.

[0098] Table 1. Information on patients in different groups

[0099] Case group Number of cases / n Gender / Example Age range Average age (in years) Course of disease Experiment 1 30 22 males, 8 females 4-15 years old 7.73±1.88 1-3 years Experimental Group 2 30 23 males, 7 females 4-15 years old 7.93±1.75 1-4 years control group 30 20 men, 10 women 4-15 years old 8.27±1.56 1-4 years

[0100] 1.2 Inclusion criteria for cases:

[0101] ① The classification and diagnosis of pediatric tic disorders, and the TCM syndrome differentiation, generally choose Tourette syndrome (TS) or chronic motor or vocal tic disorder (CTD);

[0102] ② Disease course: Tic disorders are mostly chronic, with a course of more than 1 year. It is recommended that the disease course be longer than 1 year for the selected patients.

[0103] ③ Age between 3 and 18 years old;

[0104] ④ Informed consent, and acceptance of the prescribed treatment plan and requirements;

[0105] ⑤ Other Chinese and Western medicines for treating TD were discontinued 14 days before entering the clinical study.

[0106] The diagnostic criteria for childhood tic disorders include both Western and Traditional Chinese medicine criteria, as follows:

[0107] The diagnostic criteria in Western medicine are based on the fifth revised edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V-TR, 2014).

[0108] The TCM diagnostic criteria refer to the "Guidelines for Diagnosis and Treatment of Common Pediatric Diseases in Traditional Chinese Medicine" (2012) and the "Phlegm-Fire Disturbing the Mind Syndrome" in "Traditional Chinese Medicine Pediatrics".

[0109] 1.3 Exclusion criteria:

[0110] ① Individuals with transient tic disorder and treatment-resistant tic disorder;

[0111] ②Those who do not meet the inclusion criteria, cannot take medication as prescribed, or cannot cooperate with treatment;

[0112] ③ Secondary tic disorders caused by certain medications or internal medical conditions (such as Huntington's disease or viral encephalitis).

[0113] ④ Allergic to the test drug or its components.

[0114] 1.4 Criteria for exclusion and dropout of cases:

[0115] ①Those who do not follow the established treatment plan after being selected;

[0116] ②Poor patient compliance; patients were unable to adhere to treatment.

[0117] ③ Incomplete observation items during treatment, affecting the judgment of efficacy;

[0118] ④ Those who experience serious adverse events and / or complications during treatment;

[0119] ⑤ Treatment was interrupted for more than 10 days for various reasons.

[0120] 1.5 Treatment methods:

[0121] Experimental Group 1: A decoction for clearing heat and resolving phlegm was prepared orally using the formula from Example 4. Oral administration method: Decoct in water and take one dose every two days, divided into three oral administrations.

[0122] Experimental Group 2: Oral administration. Using the formula from Example 4, a concentrated solution was prepared according to method (4), and then excipients were added to prepare granules, namely, Qinghuo Ditan Granules. Oral administration method: Dissolve in water. 3-7 years old: 1 sachet / time, 3 times / day. 8-12 years old: 1.5 sachets / time, 3 times / day. 13-18 years old: 2 sachets / time, 3 times / day. Each sachet contains 9g.

[0123] Control group: Oral administration of sulphide tablets (Jiangsu Tasly Diyi Pharmaceutical Co., Ltd., specification 0.1 dose × 100 tablets, National Drug Approval Number H32026011), dosage: 50mg dose each time for children aged 4-7, 75mg dose each time for children aged 7-12, and 100mg dose each time for children aged 12-18, 1-2 times a day.

[0124] All three groups were treated for 4 weeks as one course of treatment, and the efficacy was determined after 3 courses of treatment.

[0125] 1.6 Criteria for Evaluating Therapeutic Effect

[0126] 1.6.1 Clinical efficacy evaluation criteria: The improvement rate of the Yale Tourette Severity Scale (YGTSS) score was used as the criterion for evaluating the efficacy of the treatment. Clinical control: Complete remission of tic episodes, even if occasional mild episodes occur, they can be relieved without medication; YGTSS score improvement rate ≥90%; Significant effect: Tic episodes are significantly reduced compared to before treatment: YGTSS score improvement rate ≥60%, but <90%; Effective: Tic symptoms are somewhat reduced: YGTSS score improvement rate ≥30%, but <60%; Ineffective: Clinical symptoms do not improve or even worsen; YGTSS score improvement rate <30%.

[0127] YGTSS score improvement rate = [(Total score before treatment - Total score after treatment) / Total score before treatment] × 100%

[0128] 1.6.2 The criteria for judging the efficacy of TCM syndromes were formulated with reference to the 2002 trial version of the "Guiding Principles for Clinical Research of New Chinese Medicines". Clinical cure: TCM clinical symptoms and signs disappear or basically disappear, and the syndrome score decreases by ≥95%; Significant effect: TCM clinical symptoms and signs are significantly improved, and the syndrome score decreases by ≥70%; Effective: TCM clinical symptoms and signs are improved, and the syndrome score decreases by ≥30%; Ineffective: TCM clinical symptoms and signs are not significantly improved, or even aggravated, and the syndrome score decreases by less than 30%.

[0129] Note: The calculation formula (nimodipine method) is: [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × 100%;

[0130] Efficacy rate = (clinical control + significant effect + effective) / n × 100%.

[0131] 1.7 Safety evaluation: (1) The TESS scale was used to assess adverse drug reactions. (2) General physical examination and routine blood, stool and urine tests, liver and kidney function tests and electrocardiogram.

[0132] 1.8 Statistical Methods SPSS 23.0 statistical software was used for statistical analysis. t-tests were used for continuous data, and χ² tests were used for categorical data. 2 The test was performed, with P < 0.05 considered statistically significant.

[0133] 2. Clinical Results and Analysis

[0134] 2.1 The comparison of clinical efficacy among the three groups of patients is shown in Table 2.

[0135] 2.2 The comparison of the TCM syndrome efficacy among the three groups of patients is shown in Table 3.

[0136] 2.3 The comparison of YGTSS scores and TCM syndrome scores before and after treatment in the three groups of patients is shown in Table 4.

[0137] Table 2 Comparison of clinical efficacy among the three groups of patients (n=1)

[0138]

[0139]

[0140] Note: *P<0.05 compared with the control group.

[0141] Table 3 Comparison of TCM syndrome efficacy among the three groups of patients (cases, percentages)

[0142]

[0143] Note: *P<0.05 compared with the control group.

[0144] Table 4 Comparison of YGTSS scores and TCM syndrome scores before and after treatment in the three groups of patients ( point)

[0145]

[0146] Note: Compared with the group before and after treatment, *P<0.05; compared with the control group after treatment, #P<0.05.

[0147] The results in Tables 2-4 show that:

[0148] (1) In terms of clinical efficacy, the total effective rate of experimental group 1 was 20% higher than that of the control group, and the total effective rate of experimental group 2 was 23.3% higher than that of the control group.

[0149] (2) In terms of the efficacy of TCM syndromes, the total effective rate of experimental group 1 was 23.3% higher than that of the control group, and the total effective rate of experimental group 2 was 26.7% higher than that of the control group.

[0150] (3) In terms of YGTSS score and TCM syndrome score, the experimental group also showed better treatment effect than the control group, with the experimental group 2 showing the best effect.

[0151] 2.4 Adverse Reactions

[0152] According to relevant adverse reaction records and TESS scale assessment results, no serious adverse reactions occurred in any of the three groups during the 12-week treatment period. Adverse reactions in the control group included mild drowsiness in 2 cases, dizziness in 1 case, and nausea in 1 case; all were tolerable or resolved spontaneously without specific treatment. The experimental group had significantly fewer adverse reactions than the control group, with only 1 case experiencing mild diarrhea, which resolved spontaneously without specific treatment. The experimental group had no adverse reactions. Before and after treatment, no abnormalities were observed in the three routine blood tests, liver and kidney function tests, or electrocardiograms in any of the three groups.

[0153] 3. Typical Cases

[0154] Case 1: Chen, male, 10 years and 9 months old. Chief complaint: Vocalizations accompanied by limb twisting for 2 months. Present illness: Relevant examinations were completed at another hospital: Yale score 42 (moderate), cranial MRI, EEG, and ceruloplasmin were normal. Diagnosed with tic disorder, and prescribed oral sulpiride 0.1g / time, twice daily. The condition was poorly controlled. Current symptoms: Vocalizations, paroxysmal forceful twisting of the whole body, nose wringing, eye rolling, irritability, coprolalia, excessive sweating, good spirits, preference for rich and fatty foods, vivid dreams during sleep, constipation, and yellow urine. Red tongue with yellow and greasy coating, slippery and rapid pulse. Traditional Chinese medicine diagnosis: Convulsions - Phlegm-fire disturbance syndrome; Western medicine diagnosis: Tic disorder; Treatment principle: Clear heat and eliminate phlegm, calm wind and stop movement. Treatment with Qinghuo Ditan Decoction. After one month of medication, the frequency and intensity of the tics were reduced, and the vocalizations ceased. Occasionally, there were limb twisting and eye rolling. Irritability was reduced, and I had fewer dreams while sleeping. After another two months of treatment, all symptoms disappeared. Follow-up for several months showed no recurrence.

[0155] Case 2: Zheng, male, 8 years old. Chief complaint: Intermittent throat clearing accompanied by nasal "coughing" sounds for over a year. Present history: Relevant examinations completed at another hospital: Yale score 32 (moderate), cranial MRI showed no abnormalities, pediatric EEG, ceruloplasmin, and anti-O were all normal. Diagnosed with tic disorder, intermittently treated with sulpiride, with relapses. Current symptoms: Throat-clearing cough, nasal "coughing" sounds, sniffing, nasal congestion, thick nasal discharge, irritability, occasional coprolalia, halitosis, excessive sweating, good spirits, preference for spicy and irritating foods, hyperactivity during sleep, occasional startling awakening, constipation, yellow urine. Red tongue with yellow greasy coating, wiry and slippery pulse. Traditional Chinese medicine diagnosis: Convulsions - phlegm-fire disturbance syndrome; Western medicine diagnosis: Tic disorder; Treatment principle: Clear heat and eliminate phlegm, calm wind and stop movement. Treatment with Qinghuo Ditan granules. Two weeks after taking the medication, the cough and nasal "coughing" were reduced, and the nasal congestion and runny nose disappeared. The irritability and foul language were reduced, and the patient slept soundly. After another six weeks of treatment, all symptoms disappeared. The patient was advised to regulate his emotions, balance work and rest, eat a light diet, and avoid emotional stimulation and looking at electronic products. After several months of follow-up, there was no recurrence.

[0156] Case 3: Qiao, female, 5 years old. Chief complaint: Throat clearing accompanied by phlegm in the throat for 3 months. Present illness: Relevant examinations were completed at another hospital: Yale score 38 (moderate), routine EEG normal. Diagnosed as tic disorder, no treatment was given. Current symptoms: Throat clearing, phlegm in the throat, sniffing, occasional dizziness, vivid dreams, craving for fatty and sweet foods, irritability, bitter taste in the mouth, dry mouth, constipation, scanty dark urine, red tongue with yellow and greasy coating, slippery and rapid pulse. Traditional Chinese medicine diagnosis: Convulsions - Phlegm-fire disturbance syndrome; Western medicine diagnosis: Tic disorder; Treatment principle: Clear fire and eliminate phlegm, calm wind and stop movement. Treatment with Qinghuo Ditan Decoction. After one month of medication, the symptoms of throat clearing, phlegm in the throat, and sniffing were reduced. Dizziness, irritability, and vivid dreams improved. After another 2 months of treatment, all symptoms disappeared. Follow-up for several months showed no recurrence.

[0157] In summary, this study used a randomized, controlled method to evaluate the clinical efficacy and safety of Qinghuo Ditan Decoction and its granules. The results showed that Qinghuo Ditan Decoction was more effective than sulpiride and had a higher safety profile, indicating that Qinghuo Ditan Decoction is a relatively safe and effective drug for treating tic disorders.

[0158] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating childhood tic disorders, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: Pinellia ternata 6-9 parts, Gardenia jasminoides 6-10 parts, Bambusa textilis 3-6 parts, Arisaema cum Bile 3-6 parts, Acorus tatarinowii 6-10 parts, Curcuma longa 5-12 parts, Uncaria rhynchophylla 5-12 parts, Margarita 10-20 parts, Angelica dahurica 3-9 parts, Citrus reticulata 6-10 parts, Poria cocos 6-12 parts, Atractylodes macrocephala 6-12 parts, Codonopsis pilosula 6-12 parts, Buthus martensii 3-5 parts.

2. The traditional Chinese medicine composition for treating childhood tic disorders according to claim 1, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: Pinellia ternata 8g, Gardenia jasminoides 8g, Bambusa textilis 6g, Arisaema cum bile 5g, Acorus tatarinowii 8g, Curcuma longa 8g, Uncaria rhynchophylla 10g, Margarita 18g, Angelica dahurica 9g, Citrus reticulata 9g, Poria cocos 12g, Atractylodes macrocephala 9g, Codonopsis pilosula 12g, Scorpion 3g.

3. The traditional Chinese medicine composition for treating childhood tic disorders according to claim 1 or 2, characterized in that, The preparation made from the traditional Chinese medicine composition can be any one of decoction, granules, powder, tablets, oral liquid, or capsules.

4. A method for preparing a traditional Chinese medicine composition for treating childhood tic disorders, characterized in that, The method includes extracting the active ingredients by decoction, wherein the decoction steps are as follows: weigh the Chinese medicinal materials as described in any one of claims 1-2; add water and decoct twice, each time for at least 0.5 hours; filter and combine the decoction liquids.

5. The method for preparing the traditional Chinese medicine composition for treating childhood tic disorders according to claim 4, characterized in that, The decoction is concentrated to a viscous paste. An ethanol solution is added to the viscous paste product for alcohol precipitation, followed by standing, filtration, and concentration.

6. A method for preparing a traditional Chinese medicine composition for treating childhood tic disorders, characterized in that, The method includes extracting the effective components of the Chinese medicinal materials as described in any one of claims 1-3 by means of ethanol extraction, wherein the steps of ethanol extraction are as follows: adding ethanol solution for reflux extraction, filtering the extract, and then concentrating the extract.

7. The method for preparing the traditional Chinese medicine composition for treating childhood tic disorders according to claim 6, characterized in that, The concentration of the ethanol solution is 60-70%, and the extraction process is carried out in an ultrasonic manner.

8. The method for preparing the traditional Chinese medicine composition for treating childhood tic disorders according to claim 6 or 7, characterized in that, The extract was concentrated to obtain a concentrate, which was then purified using D101 macroporous resin.

9. The application of the traditional Chinese medicine composition for treating tic disorders in children as described in any one of claims 1-3 in the treatment of tic disorders in children with phlegm-fire disturbance syndrome.

Images