A traditional Chinese medicine preparation for treating Tourette syndrome in children with abnormal laryngeal voice as main symptom

Abstract

The present application provides a kind of traditional Chinese medicine preparation for treating Tourette syndrome of children with laryngeal abnormal voice as main symptom, the traditional Chinese medicine preparation includes the following weight parts of raw medicinal materials: 8-15 parts of radix isatidis, 3-6 parts of radix sophorae tonkinensis, 10-15 parts of radix puerariae, 6-10 parts of jinyu longan, 6-10 parts of momordica grosvenori, 6-8 parts of platycodon grandiflorum, 3-6 parts of licorice, 5-8 parts of periostracum cicada, 10 parts of radix angelicae, and addition and subtraction according to different indications, the traditional Chinese medicine preparation of the present application can clear lung and stomach heat, benefit throat, block the way of external wind driving internal wind, can rapidly and effectively treat pediatric vocal tic, improve laryngeal voice symptoms, also can treat exogenous heat syndrome sore throat, and the traditional Chinese medicine preparation of the present application is safe, no obvious toxic side effects, suitable for children to take when laryngeal abnormal voice.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, specifically to a traditional Chinese medicine preparation for treating pediatric tic disorders (chronic vocal tic disorder, transient tic disorder, and Tourette syndrome with abnormal vocalizations of the larynx as the main symptom). Background Technology

[0002] Childhood tic disorders are among the most common neuropsychiatric disorders in childhood, primarily characterized by motor tics and / or vocal tics. Vocal tics mainly involve involuntary tics of the muscles of the mouth, throat, and nose, manifesting as unusual sounds such as grunting, shouting, gurgling, groaning, barking, crowing, dolphin-like sounds, or even coprolalia. The incidence has been rising in recent years, with a male-to-female ratio of approximately 4:1. These disorders severely impact children's learning and social functioning, leading to a decline in the quality of life for both children and their families.

[0003] Currently, there are few clinical reports on the treatment of vocal tics with traditional Chinese medicine. Most doctors believe that the location of vocal tics is in the throat, which is related to the lungs and stomach, and also depends on other meridians and organs. Shen Honglian et al. summarized the pathogenesis of vocal tics as the imbalance of the ascending and descending of Qi in the lungs and stomach, the accumulation of phlegm and toxins in the throat, and the abnormal nourishment and protection of Qi and blood. Chen Mingzhou et al. reported that although vocal tics are related to all five organs, they are mainly related to the lungs and stomach.

[0004] Currently, the treatment of childhood tic disorders often involves Western medicines such as sulpiride, haloperidol, clonidine, aripiprazole, and risperidone. These medicines have adverse effects such as loss of appetite, drowsiness, fatigue, dizziness, and low blood pressure. Furthermore, Western medicines are less effective in treating vocal tics compared to motor tics. Summary of the Invention

[0005] The purpose of this invention is to provide an oral traditional Chinese medicine preparation for treating pediatric tic disorders with significant efficacy, high cure rate, and no toxic side effects, primarily characterized by abnormal vocalizations in the throat.

[0006] The technical solution adopted by this invention to solve its technical problem is a traditional Chinese medicine preparation for treating childhood tic disorders with abnormal vocalization as the main symptom. It is made from the following Chinese herbal raw materials in parts by weight: 8-15 parts of Isatis root, 3-6 parts of Sophora root, 10-15 parts of Phragmites rhizome, 6-10 parts of Golden Fruit, 6-10 parts of Luo Han Guo, 6-8 parts of Platycodon root, 3-6 parts of Licorice root, 5-8 parts of Cicadae periostracum, and 10 parts of Angelica dahurica.

[0007] The aforementioned traditional Chinese medicine preparation for treating childhood tic disorders, with abnormal vocalizations as the primary symptom, also contains: 5-8 parts Magnolia biondii, 5-8 parts stir-fried Xanthium sibiricum, and 8-10 parts Cynanchum paniculatum, and is suitable for tic disorders induced by external wind.

[0008] The aforementioned traditional Chinese medicine preparation for treating childhood tic disorders, with abnormal vocalizations as the main symptom, also contains: 6-10 parts of Pinellia ternata, 6-10 parts of Magnolia officinalis, 6-10 parts of Perilla frutescens, 8-10 parts of Poria cocos, and 8-10 parts of fresh ginger, and is suitable for phlegm-qi obstruction syndrome.

[0009] The aforementioned traditional Chinese medicine preparation for treating childhood tic disorders, with abnormal vocalizations as the main symptom, also contains: 10-20 parts of white peony root, 6-10 parts of papaya, 6-10 parts of ginger-processed pinellia, 8-10 parts of inula flower, and 15-20 parts of hematite, and is suitable for wind-phlegm disturbance syndrome.

[0010] The traditional Chinese medicine preparation for treating childhood tic disorders with abnormal vocalizations as the main symptom is prepared as follows: Weigh each herb according to the specified ratio, add water and decoct twice, one hour each time. Filter the decoction, combine the filtrates, concentrate into a clear paste, add ethanol, let stand, filter, recover the ethanol from the filtrate and concentrate into a thick paste, wait for the temperature to drop to 60℃, refrigerate for more than 12 hours, filter, concentrate, and add pharmaceutically acceptable excipients to prepare the preparation.

[0011] The traditional Chinese medicine preparation for treating childhood tic disorders with abnormal vocalizations as the main symptom includes, in the form of, oral liquid, compound preparation, decoction, pill, capsule, tablet, powder or granule.

[0012] The traditional Chinese medicine preparation for treating childhood tic disorders, with abnormal vocalizations as the main symptom, is prepared as follows: Weigh each herb according to the specified ratio, add water and decoct twice, one hour each time. Filter the decoction, combine the filtrates, concentrate into a clear paste, add ethanol, let stand, filter, recover the ethanol from the filtrate and concentrate into a thick paste. When the temperature drops to 60℃, refrigerate for more than 12 hours and filter. Separately, take sucrose, add water and boil to make syrup, add 0.6% cyclamate to dissolve, combine with the above decoction, fill, sterilize, and prepare one of the following: oral liquid, compound preparation, or decoction.

[0013] The traditional Chinese medicine preparation for treating childhood tic disorders with abnormal vocalizations as the main symptom includes pharmaceutically acceptable excipients such as diluents, fillers, disintegrants, lubricants, binders, flow agents, complexing agents, plasticizers, colorants, sweeteners, viscosity enhancers, preservatives, or antioxidants.

[0014] The traditional Chinese medicine preparation for treating childhood tic disorders, with abnormal vocalizations as the primary symptom, comprises the following components: the diluent includes one or more of sorbitol, mannitol, starch, lactose, powdered or microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, and sugar; the filler includes one or more of sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, and gelatinized starch; the disintegrant includes one or more of dry starch, crospovidone, crospovidone carboxymethyl cellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose; and the lubricant includes one or more of magnesium stearate, sodium dodecyl sulfate, and micronized silica gel.

[0015] The application of traditional Chinese medicine preparations for treating pediatric tic disorders, with abnormal vocalizations as the main symptom, in the preparation of drugs for treating pediatric tic disorders.

[0016] Beneficial effects:

[0017] Ancient physicians lacked a precise record and understanding of the etiology and pathogenesis of vocal tic disorders. Descriptions of related symptoms are scattered across various schools of thought, but the pathological factors are widely considered to be wind, fire, and phlegm, with the onset related to dysfunction of the liver, spleen, and kidneys. The *Suwen* (Plain Questions) states, "All dizziness and vertigo belong to the liver," indicating that the location of the tic is in the liver, with wind and phlegm disturbance as the main causes. "All mania and agitation belong to fire," indicating that this disease belongs to Yang and fire, and is related to wind and phlegm. The *Youyou Jicheng* (Collection of Infant Formulas) describes infantile convulsions as "a liver disease, but also a disease of the spleen, kidneys, heart, and lungs," indicating that all five organs can cause the disease, not just the liver. Traditional Chinese medicine believes that the location of vocal tic disorders is in the throat, closely related to the lungs and stomach. The *Suwen* states, "Clear Yang exits through the upper orifices, turbid Yin exits through the lower orifices." Clear Yang refers to the essence of Qi and blood, which is the material basis for nourishing the body and orifices. The heart and lungs reside in the upper burner, governing clear yang. When the heart and lungs are healthy, qi flows smoothly, and this smooth flow propels blood circulation, just as stated in the *Suwen* (Plain Questions) chapter "On the Six Sections and Visceral Manifestations": "The five qi enter through the nose, are stored in the heart and lungs, and above, they make the five colors bright and the voice clear." Turbid yin refers to metabolic byproducts such as water, phlegm, and food waste. The spleen and stomach reside in the middle burner, governing the ascending of clear qi and the descending of turbid qi. A healthy spleen and stomach help to expel turbid yin from the body. "The throat is related to the lungs" (*Wenbing Tiaobian*). The throat is governed by the lungs; impaired lung function easily leads to throat discomfort and abnormal voice. When wind, heat, and dampness stagnate in the lungs, lung qi fails to circulate, and the internal and external forces clash in the throat, resulting in throat clearing, coughing, and phlegm. Damage to the spleen and stomach easily generates phlegm and dampness. "The spleen is the source of phlegm, and the lungs are the receptacle of phlegm." Phlegm and dampness obstruct the throat, causing a feeling of phlegm blockage, expectoration of white, sticky phlegm, or even clouding the mind, resulting in strange noises, foul language, and coarse speech.

[0018] Based on the application of the theory of "ascending and descending of clear and turbid substances" in the study of the pathogenesis of diseases of the ear, nose, and throat, the etiology and pathogenesis of vocal tics can be summarized as follows: heat rising from the lungs and stomach, coupled with the invasion of external wind-heat pathogens, leads to the accumulation of internal and external toxins in the throat. This scorches the body fluids, transforming them into phlegm. The accumulation of phlegm and fire then triggers internal wind, and the struggle between these two winds stirs the throat, producing abnormal sounds. The primary location of vocal tics is in the throat, lungs, and stomach, closely related to the liver and spleen. Its root cause is dietary indiscretion and damage to the spleen and stomach, while its manifestations are phlegm, fire, and wind.

[0019] After a cold, the tics in children, especially abnormal vocalizations in the throat, tend to worsen or recur. We believe that external wind triggering internal wind is the reason for the recurrence of symptoms in some children. Wind is the source of many diseases, and the throat is the gateway to the lungs and stomach. The liver governs the free flow of qi and regulates swallowing. When the qi flows smoothly, swallowing is unobstructed. At the same time, the liver stores blood and nourishes the throat. The throat receives blood and can produce sound. Vocal tics are closely related to the liver, lungs, and stomach. Nowadays, children often like to eat fried and stir-fried foods, which triggers the upward steaming of heat in the lungs and stomach. Coupled with the invasion of wind-heat external pathogens, internal and external pathogens combine in the throat, scorching the body fluids and turning them into phlegm. The accumulation of phlegm and fire triggers internal wind, resulting in this disease. Treatment focuses on clearing heat and detoxifying. The main principle is to soothe the throat and stop coughing. In the early stage, when external wind is prevalent, the path of external wind to induce internal wind should be blocked. If there is nasal snoring, nasal itching, sneezing, nasal congestion, runny nose, and sneezing, add magnolia flower, fried cocklebur fruit, and cynanchum paniculatum to open the nasal passages (external wind-induced syndrome). In the middle stage, when phlegm and qi are obstructed, such as a foreign body sensation in the throat, difficulty swallowing, or inability to spit out, add Banxia Houpu Decoction (prepared pinellia, magnolia bark, perilla leaf, poria, and ginger) to regulate qi, resolve phlegm, and disperse nodules (phlegm and qi obstruction syndrome). Or if the throat sounds are accompanied by abdominal twitching, add white peony root, papaya, ginger pinellia, inula flower, and hematite to descend the adverse qi, resolve phlegm, and relieve urgency (wind-phlegm disturbance syndrome).

[0020] The theoretical basis of the basic formula in Traditional Chinese Medicine:

[0021] The principal herbs are: Isatis root, which enters the liver and stomach blood level and has the functions of clearing heat and detoxifying (clearing stomach fire), cooling blood, and relieving sore throat; Sophora root enters the heart, lung, and stomach meridians (clearing lung and stomach fire) and is "the first essential medicine for purging the heart and protecting the lungs, as well as reducing the fire in the yin meridians and relieving sore throat". The two herbs are combined as the principal herbs and have the function of clearing lung and stomach fire and relieving sore throat.

[0022] Assistant herbs: Reed rhizome is sweet and cold in nature, and functions to clear lung heat and generate body fluids. It assists Isatis root and Sophora root in clearing lung and stomach heat, detoxifying and relieving sore throat. In addition, the sweet reed rhizome in compound preparations can improve the taste of Chinese medicine. Cicada molting is sweet, salty and cool, and enters the lung and liver meridians. It functions to dispel wind, clear heat and relieve sore throat. The two herbs together are assistant herbs, which help the principal herbs to enhance the effects of clearing heat and relieving sore throat. They can also dispel wind and stop spasms, and block the path of external wind to induce internal wind.

[0023] The adjuvant herbs are: Golden olive (Golden Fruit) enters the lung and large intestine meridians, clearing heat and detoxifying, relieving sore throat and pain, and also promoting body fluid production; Monk fruit (Luo Han Guo) is cool in nature and sweet in taste, entering the lung and large intestine meridians, with the effects of clearing the lungs and relieving sore throat, resolving phlegm and relieving cough, and moistening the intestines and promoting bowel movements. Its sweet taste, combined with reed rhizome, can improve the taste of traditional Chinese medicine, which is beneficial for improving children's medication compliance; Platycodon root (Jie Geng) floats upward and protects the lungs, and can benefit the throat. Combined with licorice root, it forms Gan Jie Tang (Licorice and Platycodon Decoction) to treat throat diseases; Vocal tics are often accompanied by allergic rhinitis, and the above herbs are mostly bitter and cold. Adding warm angelica root (Bai Zhi) can not only clear the nasal passages but also counteract the bitter and cold nature of the herbs, preventing them from harming the stomach.

[0024] Adjuvant: Licorice harmonizes the effects of other herbs.

[0025] When used together, these herbs clear heat from the lungs and stomach, soothe the throat, and stop external wind, thus blocking the pathway by which external wind triggers internal wind. With the throat benefited, the coughing stops. Clinical observations show that heat-clearing and throat-soothing herbs are the most frequently used in prescriptions for vocal tics.

[0026] The basic formula also has the effect of promoting body fluid production; the modified formula one is the basic formula plus magnolia flower, cocklebur fruit, and cynanchum paniculatum, which also has the effect of anti-allergy (external wind-induced syndrome); the modified formula two is the basic formula plus pinellia and magnolia bark decoction, which also has the effect of pungent opening and bitter descending, resolving phlegm and dissipating nodules. Pinellia and magnolia bark decoction has the effect of regulating the transmission of nerve excitation in the body through pathways such as 5-HT synapses (phlegm and qi obstruction syndrome); the modified formula three is the basic formula plus inula and hematite decoction, which also has the effect of resolving phlegm and descending rebellious qi (wind-phlegm disturbing the upper body syndrome). Detailed Implementation

[0027] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the description of this invention, those skilled in the art can make various alterations or modifications to the invention, but these equivalent forms are also embodied within the scope defined by the appended claims.

[0028] Example 1:

[0029] Take 1000g of Isatis root, 500g of Sophora root, 1000g of Phragmites rhizome, 1000g of Golden Fruit, 600g of Siraitia fruit, 600g of Platycodon root, 500g of Licorice root, 600g of Cicadae periostracum, and 1000g of Angelica dahurica. Weigh each herb according to the proportions, add 10 times their weight of water and decoct twice, 1 hour each time. Filter the decoction, combine the filtrates, concentrate into a clear paste, add 95% ethanol to adjust the alcohol concentration to 75%, let stand, filter, recover the ethanol from the filtrate and concentrate into a thick paste. When the temperature drops to 60℃, refrigerate for more than 12 hours and filter. Separately, take 150g of sucrose, add water and boil to make syrup, add 0.6% cyclamate to dissolve, combine with the above decoction, add water to adjust to 10000ml, fill, sterilize, and prepare the mixture.

[0030] Example 2:

[0031] Take 1000g of Isatis root, 500g of Sophora root, 1000g of Phragmites rhizome, 1000g of Golden Fruit, 600g of Siraitia fruit, 600g of Platycodon root, 500g of Licorice root, 600g of Cicadae periostracum, 1000g of Angelica dahurica, 600g of Magnolia flower bud, 600g of stir-fried Xanthium fruit, and 900g of Cynanchum paniculatum. Weigh each herb according to the proportions, add 10 times their weight of water and decoct twice, 1 hour each time. Filter the decoction, combine the filtrates, concentrate into a clear paste, add 95% ethanol to adjust the alcohol concentration to 75%, let stand, filter, recover the ethanol from the filtrate and concentrate into a thick paste. When the temperature drops to 60℃, refrigerate for more than 12 hours and filter. Separately, take 150g of sucrose, add water and boil to make syrup, add 0.6% cyclamate to dissolve, combine with the above decoction, add water to adjust to 10000ml, fill, sterilize, and prepare the mixture.

[0032] In the above preparation method, Magnolia biondii is prepared by wrapping and decocting.

[0033] Example 3:

[0034] Take 1000g of Isatis root, 500g of Sophora root, 1000g of reed rhizome, 1000g of goldenrod, 600g of monk fruit, 600g of platycodon root, 500g of licorice root, 600g of cicada slough, 1000g of angelica root, 800g of prepared pinellia tuber, 800g of magnolia bark, 800g of perilla leaf, 1000g of poria cocos, and 900g of fresh ginger. Weigh each herb according to the proportions, add 10 times their weight of water, and decoct twice, one hour each time. The decoction was filtered, the filtrates were combined, and concentrated into a clear paste. 95% ethanol was added to adjust the alcohol concentration to 75%. The mixture was allowed to stand, filtered, and the ethanol was recovered from the filtrate and concentrated into a thick paste. When the temperature dropped to 60℃, it was refrigerated for more than 12 hours and then filtered. Separately, 150g of sucrose was boiled with water to make a syrup. 0.6% cyclamate was added to dissolve the syrup and combined with the above decoction. Water was added to adjust the volume to 10000ml, and the mixture was bottled, sterilized, and prepared into a compound preparation.

[0035] Example 4:

[0036] Take 1000g of Isatis root, 500g of Sophora root, 1000g of Phragmites rhizome, 1000g of Golden Fruit, 600g of Siraitia fruit, 600g of Platycodon root, 500g of Licorice root, 600g of Cicadae periostracum, 1000g of Angelica dahurica, 1500g of White peony root, 800g of Chaenomeles speciosa, 800g of Pinellia ternata, 900g of Inula flower, and 1800g of Hematite. Weigh each herb according to the proportions, add 10 times their weight of water, and decoct twice, one hour each time. The decoction was filtered, the filtrates were combined, and concentrated into a clear paste. 95% ethanol was added to adjust the alcohol concentration to 75%. The mixture was allowed to stand, filtered, and the ethanol was recovered from the filtrate and concentrated into a thick paste. When the temperature dropped to 60℃, it was refrigerated for more than 12 hours and then filtered. Separately, 150g of sucrose was boiled with water to make a syrup. 0.6% cyclamate was added to dissolve the syrup and combined with the above decoction. Water was added to adjust the volume to 10000ml, and the mixture was bottled, sterilized, and prepared into a compound preparation.

[0037] Example 5:

[0038] Take 1000g of Isatis root, 500g of Sophora root, 1000g of Phragmites rhizome, 1000g of Golden Fruit, 600g of Siraitia fruit, 600g of Platycodon root, 500g of Licorice root, 600g of Cicadae periostracum, and 1000g of Angelica dahurica. Weigh each herb according to the proportions, add 10 times their weight of water and decoct twice, 1 hour each time. Filter the decoction, combine the filtrates, concentrate into a clear paste, add 95% ethanol to adjust the alcohol concentration to 75%, let stand, filter, recover the ethanol from the filtrate and concentrate into a thick paste. When the temperature drops to 60℃, refrigerate for more than 12 hours, filter, concentrate, add starch, and prepare into tablets.

[0039] Example 6:

[0040] Take 1000g of Isatis root, 500g of Sophora root, 1000g of Phragmites rhizome, 1000g of Golden Fruit, 600g of Siraitia fruit, 600g of Platycodon root, 500g of Licorice root, 600g of Cicadae periostracum, 1000g of Angelica dahurica, 600g of Magnolia biondii, 600g of stir-fried Xanthium fruit, and 900g of Cynanchum paniculatum. Weigh each herb according to the proportions, add 10 times their weight of water and decoct twice, 1 hour each time. Filter the decoction, combine the filtrates, concentrate into a clear paste, add 95% ethanol to adjust the alcohol concentration to 75%, let stand, filter, recover the ethanol from the filtrate and concentrate into a thick paste. When the temperature drops to 60℃, refrigerate for more than 12 hours, filter, concentrate, add dextrin, and prepare capsules.

[0041] In the above preparation method, Magnolia biondii is prepared by wrapping and decocting.

[0042] Example 7: Clinical Research Observation

[0043] I. Research Objective: To investigate the efficacy of the traditional Chinese medicine preparation of this invention in treating childhood tic disorders characterized primarily by abnormal vocalizations in the throat.

[0044] II. Research Content:

[0045] (a) Research Design: Open-ended Experiment.

[0046] (II) Case selection: All cases were 130 children who were clinically diagnosed with Tourette syndrome (mainly vocal) at the outpatient clinic of Professor Han Xinmin in the Department of Pediatrics of Jiangsu Provincial Hospital of Traditional Chinese Medicine from January 2019 to January 2020.

[0047] (III) Diagnostic and therapeutic criteria

[0048] 1. Diagnostic criteria

[0049] (1) Western medicine diagnostic criteria (based on the DSM-V diagnostic criteria for tic disorders)

[0050] 1) Tourette's Disorder

[0051] a. Multiple motor tics and one or more vocal tics are present for a period of time during the illness, although they may not occur simultaneously. b. The frequency of the tics may vary in intensity, but they persist for more than one year from the onset of the first tic.

[0052] c. Occurred before the age of 18.

[0053] d. This disorder cannot be attributed to the physiological effects of a substance (e.g., cocaine) or other physical illnesses (e.g., Huntington's disease, postviral encephalitis).

[0054] 2) Chronic vocal tic disorder

[0055] a. Single or multiple vocal tics persist throughout the course of the disease.

[0056] b. The frequency of tics can vary in strength, but they must persist for at least one year from the first occurrence of the tics.

[0057] c. Occurred before the age of 18.

[0058] d. This disorder cannot be attributed to the physiological effects of a substance (e.g., cocaine) or other physical illnesses (e.g., Huntington's disease, postviral encephalitis).

[0059] e. Does not meet the diagnostic criteria for Tourette's disorder.

[0060] 3) Transient tic disorder

[0061] a. Single or multiple motor and / or vocal tics.

[0062] b. The duration of the tic is less than one year from the first occurrence.

[0063] c. Occurred before the age of 18.

[0064] d. This disorder cannot be attributed to the physiological effects of a substance (e.g., cocaine) or other physical illnesses (e.g., Huntington's disease, postviral encephalitis).

[0065] e. Does not meet the diagnostic criteria for Tourette's disorder or persistent (chronic) motor or vocal tic disorder.

[0066] (2) Traditional Chinese Medicine Diagnosis Standards

[0067] This formula was developed with reference to the Clinical Diagnosis and Treatment Guidelines for Pediatric TCM: Tic Disorders (Revised) and the experience of Professor Han Xinmin.

[0068] 1) External wind-induced symptoms

[0069] Main symptoms: unusual sounds or coarse speech in the throat, discomfort in the throat, frowning and blinking, symptoms worsen after a cold;

[0070] Secondary symptoms: irritability, fever, red or sore throat, red tongue with thin coating, and floating and rapid pulse; examination of the pharynx may reveal pharyngeal congestion, tonsil enlargement, or hyperplasia of lymphoid follicles on the posterior pharyngeal wall.

[0071] 2) Phlegm and Qi obstruction syndrome

[0072] Main symptoms: A humming sound in the throat, a foreign body sensation in the throat that cannot be swallowed or spit out;

[0073] Secondary symptoms: a feeling of phlegm in the throat, or itching and coughing in the throat; a white and greasy or sticky tongue coating; and a slippery pulse; examination of the pharynx reveals phlegm adhering to the posterior pharyngeal wall.

[0074] 3) Wind-phlegm disturbing the upper body syndrome

[0075] Main symptoms: involuntary shouting, uttering foul language, or phlegm sounds in the throat, clearing the throat, often accompanied by blinking, grimacing, limb twitching, etc.

[0076] Secondary symptoms: irritable and easily angered, poor self-control, dietary preferences, red tongue with a thin, greasy coating, and wiry pulse; pharyngeal examination reveals slight or no pharyngeal congestion, or enlarged tonsils.

[0077] 4) Liver and kidney yin deficiency syndrome

[0078] Main symptoms: prolonged course of illness, dry throat and throat clearing, or uttering foul language, or accompanied by limb tremors, muscle tension, head nodding, shoulder shrugging and other tics;

[0079] Secondary symptoms: thin build, flushed cheeks, hot palms and soles, or bedwetting, dark red tongue with little moisture and little coating, or glossy red tongue with no coating, thready and rapid pulse; pharyngeal examination shows no pharyngeal congestion.

[0080] 2. Inclusion criteria

[0081] (1) Meets the Western medical diagnostic criteria and the traditional Chinese medicine diagnostic criteria for tic disorders, and the duration of transient tic disorder in children must be greater than 3 months.

[0082] (2) Age 4-18 years old, gender not limited;

[0083] (3) Other Chinese and Western medicines for treating tic disorders were discontinued two weeks before entering the clinical trial;

[0084] (4) Did not participate in other clinical trials;

[0085] (5) With the consent of the parents or guardians.

[0086] Those who meet all five criteria can be included in the trial.

[0087] 3. Exclusion Criteria

[0088] (1) Patients who do not meet the diagnostic criteria of Western medicine and the syndrome differentiation criteria of traditional Chinese medicine;

[0089] (2) Those who have been clearly diagnosed with ADHD, chorea, Wilson's disease, autism, intellectual disability, obsessive-compulsive disorder, epilepsy, or choreoathetosis;

[0090] (3) Comorbid severe psychological and mental illnesses such as intellectual disability, pervasive developmental disorder, childhood schizophrenia, manic episodes and bipolar disorder, and specific learning skills developmental disorders;

[0091] (4) Patients with serious diseases of the cardiovascular, liver, kidney or hematopoietic system;

[0092] (5) Those with organic lesions in the brain;

[0093] (6) Drug-induced tic disorders;

[0094] (7) Other individuals with tic disorders that have not yet been defined;

[0095] (8) Those under the age of 4 or over the age of 18;

[0096] (9) Allergic to Chinese herbal decoctions or any of the herbs contained therein;

[0097] (10) Patients who have participated in other drug clinical trials within the past three months;

[0098] (11) Based on the judgment, other lesions or conditions that reduce the possibility of enrollment or complicate enrollment, such as inconvenient transportation, unstable learning and living environment, etc., which may lead to loss to follow-up, or incomplete symptom information form, may affect the researchers of this study.

[0099] If any one of these criteria is met, the individual cannot be included in the trial.

[0100] 4. Shedding Criteria

[0101] (1) The doctor decides to withdraw

[0102] 1) If the child experiences an allergic reaction or serious adverse event, and Dr. Han determines that medication should be discontinued;

[0103] 2) During the trial observation process, if the child becomes infected or develops other diseases, affecting the assessment of efficacy and safety;

[0104] 3) Children with poor compliance who refuse to take traditional Chinese medicine, or who change their medication midway through the treatment or add Western medicines prohibited by this plan, such as sulpiride and clonidine, which affect the evaluation of efficacy.

[0105] (2) The patient withdrew voluntarily.

[0106] 1) Regardless of the reason, if the patient's family is unwilling or unable to continue the clinical trial and requests to withdraw from the trial from Chief Physician Han, the trial will be stopped.

[0107] 2) Patients who, although not explicitly withdrawing from the trial, ceased receiving treatment and were lost to follow-up.

[0108] Management of shedding cases

[0109] (1) After the patient falls off the medication, we will contact the patient as much as possible by visiting the patient at home, scheduling follow-up visits, making phone calls, or sending letters, asking for the reasons, recording the last time the patient took the medication, and completing the assessment items that can be completed.

[0110] (2) If a patient withdraws from the trial due to allergies or other adverse reactions or ineffective treatment, appropriate treatment measures shall be taken according to the patient's actual condition.

[0111] (3) All data on the lost cases should be properly preserved, both for archiving and for comprehensive collection and statistical analysis.

[0112] 5. Elimination Criteria

[0113] (1) Those who were mistakenly included despite not meeting the inclusion criteria, or those who meet any of the exclusion criteria;

[0114] (2) Those who meet the inclusion criteria but have never taken medication or have no follow-up visit records. Before statistical analysis of cases, determine whether to exclude them.

[0115] 6. Severity Grading Standards

[0116] Based on the total scores for motor tics and vocal tics in the YGTSS assessment, motor tics and vocal tics are respectively classified into three levels: mild, moderate, and severe (excluding deficit scores), as follows:

[0117] Mild: 5-11 points; Moderate: 12-18 points; Severe: 19-25 points.

[0118] 7. Efficacy evaluation criteria

[0119] Based on the Yale GTSS scale, the types, frequency, intensity, complexity, impact, and deficits of tics were scored. The total scores for motor tics, vocal tics, overall deficit, and severity (total scores for vocal tics + total scores for motor tics) were calculated, and the scores before and after treatment and the decrease in scores were evaluated.

[0120] Therapeutic effect index = (Total score of tic severity before treatment - Total score of tic severity after treatment) ÷ Total score of tic severity before treatment × 100%

[0121] Clinical control: Tic symptoms have basically disappeared, the total score has decreased by ≥95%, and there has been no recurrence for more than 6 months;

[0122] Significant effect: Tics are significantly reduced, and the total score is reduced by ≥70% and <95%;

[0123] Progress: Tics have improved, and the total score has decreased by ≥30% and <70%;

[0124] Ineffective: Tics show no improvement or worsen, and the total score decreases by <30%.

[0125] Effective rate: (Number of cases with clinical control + Number of cases with significant effect) ÷ Total number of cases × 100%

[0126] Effectiveness rate: (Number of cases with clinical control + Number of cases with significant improvement + Number of cases with improvement) ÷ Total number of cases × 100%

[0127] The criteria for evaluating the efficacy of TCM syndromes were formulated with reference to the 2002 edition of the "Guiding Principles for Clinical Research of New Chinese Medicine Drugs (Trial Implementation)".

[0128] Therapeutic effect index = (Pre-treatment syndrome score - Post-treatment syndrome score) ÷ Total pre-treatment syndrome score × 100%

[0129] Clinical control: The reduction rate of syndrome score is ≥95%;

[0130] Significant effect: The reduction rate of syndrome score is ≥70% and <95%;

[0131] Effective: The reduction rate of syndrome score is ≥30% and <70%;

[0132] Invalid: The rate of reduction in syndrome score is <30%.

[0133] Effective rate: (Number of cases with clinical control + Number of cases with significant effect) ÷ Total number of cases × 100%

[0134] Effectiveness rate: (Number of cases with clinical control + Number of cases with significant improvement + Number of cases with improvement) ÷ Total number of cases × 100%

[0135] Its safety was evaluated by observing blood routine tests, liver and kidney function, electrocardiogram, and adverse events.

[0136] Level 1: Safe, no adverse reactions;

[0137] Grade 2: Relatively safe, with mild adverse reactions that require no treatment and can be continued;

[0138] Level 3: Severe adverse reactions and safety issues lead to termination of the trial.

[0139] 8. Treatment Plan

[0140] For wind-phlegm disturbance syndrome, take the compound obtained in Example 4 orally; for phlegm-qi obstruction syndrome, take the compound obtained in Example 3 orally; for external wind-induced syndrome, take the compound obtained in Example 2 orally; for liver and kidney yin deficiency syndrome, take Liuwei Dihuang Decoction (self-made) orally. Dosage: 4-6 years old: 30ml each time, three times a day; 7-9 years old: 40ml each time, three times a day; 10-14 years old: 50ml each time, three times a day; 14 years and older: 60ml each time, three times a day.

[0141] 9. Research Results

[0142] A total of 130 outpatient cases were collected, of which 7 cases were dropped and 123 cases were completed. Table 1 shows that in terms of syndrome distribution, the wind-phlegm disturbance syndrome had the highest prevalence, accounting for 42.3%, followed by phlegm-qi obstruction and external wind disturbance, accounting for 20.3% and 19.5% respectively, while liver and kidney yin deficiency was relatively the least common.

[0143] Table 1 Distribution of TCM Syndromes

[0144]

[0145] Table 2 shows that after 2 weeks of treatment: 0 cases were clinically controlled, 7 cases showed significant improvement, 64 cases showed improvement, and 52 cases were ineffective, with a significant improvement rate of 5.69% and an effective rate of 57.72%.

[0146] Table 2. Analysis of overall efficacy after 2 weeks of treatment.

[0147]

[0148] Table 3 shows that after 4 weeks of treatment: 0 cases were clinically controlled, 16 cases showed significant improvement, 69 cases showed improvement, and 38 cases were ineffective, with a significant improvement rate of 13.01% and an effective rate of 69.11%.

[0149] Table 3. Analysis of overall efficacy after 4 weeks of treatment.

[0150]

[0151] Table 4 shows that after 8 weeks of treatment: 14 cases were clinically controlled, 32 cases showed significant improvement, 53 cases showed improvement, and 24 cases were ineffective, with a significant improvement rate of 37.40% and an effective rate of 80.49%.

[0152] Table 4. Analysis of overall efficacy after 8 weeks of treatment

[0153]

[0154] Table 5 shows that after 12 weeks of treatment: 28 cases achieved clinical control, 63 cases showed significant improvement, 29 cases showed improvement, and 3 cases were ineffective, with a significant improvement rate of 73.98% and an effective rate of 97.56%. Table 6 shows the efficacy analysis based on TCM syndromes: For the syndrome of external wind disturbance, the significant improvement rate was 58.33% and the effective rate was 95.83%; for the syndrome of wind-phlegm disturbance, the significant improvement rate was 30.77% and the effective rate was 92.31%; for the syndrome of phlegm-qi obstruction, the significant improvement rate was 40.00% and the effective rate was 100.0%; and for the syndrome of liver and kidney yin deficiency, the significant improvement rate was 45.45% and the effective rate was 90.91%.

[0155] Table 5. Analysis of overall efficacy after 12 weeks of treatment.

[0156]

[0157] Table 6. Analysis of the efficacy of TCM syndromes after treatment.

[0158]

[0159] III. Research Conclusions

[0160] Through clinical collection and analysis of Professor Han Xinmin's treatment cases, it was found that Professor Han Xinmin classified pediatric vocal tic disorders into four syndrome types: external wind-induced syndrome, phlegm-qi obstruction syndrome, wind-phlegm disturbance syndrome, and liver and kidney yin deficiency syndrome. Among them, the early stage of the disease is mainly due to external wind-induced syndrome, the prolonged course of the disease is mostly due to liver and kidney yin deficiency syndrome, the wind-phlegm disturbance syndrome is more common in Tourette syndrome, and chronic (persistent) vocal tic disorders are mainly manifested as phlegm-qi obstruction syndrome. In terms of clinical efficacy, at the end of the 12-week observation period, the disease efficacy analysis showed that 28 cases achieved clinical control, 63 cases showed significant improvement, 29 cases showed improvement, and 3 cases were ineffective, with a significant efficacy rate of 73.98% and an effective rate of 97.56%. From the perspective of TCM syndrome efficacy analysis, the significant efficacy rate for external wind-induced syndrome was 58.33%, and the effective rate was 95.83%; the significant efficacy rate for wind-phlegm disturbance syndrome was 30.77%, and the effective rate was 92.31%; the significant efficacy rate for phlegm-qi obstruction syndrome was 40.00%, and the effective rate was 100.0%; and the significant efficacy rate for liver and kidney yin deficiency syndrome was 45.45%, and the effective rate was 90.91%. No adverse reactions were observed during the observation period and at the 3-month and 6-month follow-up after the end of the period.

[0161] Typical clinical cases

[0162] Patient Chen Mouhang, male, 10 years old, first visited on October 11, 2020. He had been making a coughing sound in his throat for over 8 months, occasionally blinking, and habitually rubbing and picking his nose. In the past week, he experienced nasal congestion, sneezing, and a slight cough, feeling phlegm in his throat. The coughing sound had significantly worsened, occurring approximately every 3 minutes, disturbing teachers and classmates in class. Physical examination revealed significant pharyngeal congestion, grade II-III tonsillar enlargement, follicular hyperplasia on the posterior pharyngeal wall, a red tongue with a thin coating, and a wiry and rapid pulse. Western medicine diagnosis: Transient tic disorder; Traditional Chinese medicine diagnosis: Childhood tic disorder, syndrome: External wind-induced tic syndrome. Prescription: Isatis root 10g, Sophora root 5g, Phragmites rhizome 10g, Golden fruit 10g, Luo Han Guo 10g, Platycodon root 6g, Licorice root 5g, Cicada slough 6g, Angelica dahurica 10g, Magnolia flower 6g. 包煎 6g of stir-fried Xanthium sibiricum and 9g of Cynanchum paniculatum were prescribed for 14 doses. The mixture was prepared according to the method in Example 2. After two weeks of use, the frequency of vocalizations in the throat significantly decreased, blinking decreased, nasal congestion and runny nose improved, and there was no significant cough. The tongue was slightly red with a thin coating, and the pulse was wiry. The mixture was continued for another two weeks. On November 8, 2020, at the third consultation, the vocalization symptoms had basically disappeared, there was no significant blinking, the tongue was slightly red with a thin coating, and the pulse was wiry and thready. Liuwei Dihuang Decoction with modifications was prescribed to consolidate the therapeutic effect.

[0163] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine preparation for treating pediatric tic disorders primarily characterized by abnormal vocalizations in the throat, characterized in that, It is made from the following Chinese herbal medicine ingredients in parts by weight: 8-15 parts of Isatis root, 3-6 parts of Sophora root, 10-15 parts of Phragmites rhizome, 6-10 parts of Golden Fruit, 6-10 parts of Luo Han Guo, 6-8 parts of Platycodon root, 3-6 parts of Licorice root, 5-8 parts of Cicadae periostracum, 10 parts of Angelica dahurica, 5-8 parts of Magnolia flower, 5-8 parts of stir-fried Xanthium fruit, and 8-10 parts of Cynanchum paniculatum. The tic disorder in children is the external wind-induced tic disorder.

2. A traditional Chinese medicine preparation for treating childhood tic disorders, primarily characterized by abnormal vocalizations in the throat, characterized in that... It is made from the following Chinese herbal medicine ingredients in parts by weight: 8-15 parts Isatis root, 3-6 parts Sophora root, 10-15 parts Phragmites rhizome, 6-10 parts Golden berry, 6-10 parts Luo Han Guo, 6-8 parts Platycodon root, 3-6 parts Licorice root, 5-8 parts Cicadae slough, 10 parts Angelica dahurica, 6-10 parts Pinellia ternata, 6-10 parts Magnolia officinalis, 6-10 parts Perilla leaf, 8-10 parts Poria cocos, and 8-10 parts fresh ginger. The syndrome type of childhood tic disorder is phlegm and qi obstruction syndrome.

3. A traditional Chinese medicine preparation for treating childhood tic disorders, primarily characterized by abnormal vocalizations in the throat, characterized in that... It is made from the following Chinese herbal medicine ingredients in parts by weight: 8-15 parts of Isatis root, 3-6 parts of Sophora root, 10-15 parts of Phragmites rhizome, 6-10 parts of Golden Fruit, 6-10 parts of Luo Han Guo, 6-8 parts of Platycodon root, 3-6 parts of Licorice root, 5-8 parts of Cicadae periostracum, 10 parts of Angelica dahurica, 10-20 parts of White peony root, 6-10 parts of Chaenomeles speciosa, 6-10 parts of Pinellia ternata, 8-10 parts of Inula japonica, and 15-20 parts of Hematite. The syndrome type of childhood tic disorder is wind-phlegm disturbing the upper body.

4. The traditional Chinese medicine preparation for treating childhood tic disorders with abnormal vocalizations as the main symptom, as described in any one of claims 1-3, is characterized in that... Preparation method: Weigh each Chinese herbal medicine according to the ratio, add water and decoct twice, one hour each time. Filter the decoction, combine the filtrates, concentrate into a clear paste, add ethanol, let stand, filter, recover the ethanol from the filtrate and concentrate into a thick paste. When the temperature drops to 60℃, refrigerate for more than 12 hours, filter, concentrate, and add pharmaceutically acceptable excipients to prepare the preparation.

5. The traditional Chinese medicine preparation for treating childhood tic disorders with abnormal vocalizations as the main symptom, as described in claim 4, is characterized in that... The dosage form of the traditional Chinese medicine preparation is one of the following: pills, capsules, tablets, powders, or granules.

6. The traditional Chinese medicine preparation for treating childhood tic disorders with abnormal vocalizations as the main symptom, as described in any one of claims 1-3, is characterized in that... Preparation method: Weigh each Chinese herbal medicine according to the ratio, add water and decoct twice, one hour each time. Filter the decoction, combine the filtrates, concentrate into a clear paste, add ethanol, let stand, filter, recover the ethanol from the filtrate and concentrate into a thick paste. When the temperature drops to 60℃, refrigerate for more than 12 hours and filter. Separately, take sucrose, add water and boil to make syrup, add 0.6% cyclamate to dissolve, combine with the above decoction, fill, sterilize, and prepare one of the following: oral liquid, compound preparation, or decoction.

7. The use of the traditional Chinese medicine preparation for treating pediatric tic disorders with abnormal vocalizations as the main symptom as described in any one of claims 1-3 in the preparation of drugs for treating pediatric tic disorders.

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