Traditional Chinese medicine compound composition for treating obesity with precocious puberty of children

Abstract

The invention discloses a traditional Chinese medicine compound composition for treating children obesity with sexual precocity, and relates to the field of traditional Chinese medicine preparation research. Obesity and precocious puberty are a first common disease and a second common disease of endocrine of children respectively, and meanwhile, more and more evidences show that obesity, especially obesity of girls, is closely related to occurrence of precocious puberty. At present, treatment of obesity in children is still difficult, and no effective weight-losing medicine exists in children. The invention provides a traditional Chinese medicine compound composition for treating obesity with sexual precocity of children. The traditional Chinese medicine compound composition is prepared from the following components in parts by weight: 9-15g of rhizoma anemarrhenae, 9-15g of cortex phellodendri, 15-20g of rhizoma alismatis, 10-15g of poria cocos, 6-12g of pericarpium citri reticulatae, 6-12g of processed rhizoma pinelliae, 10-20g of rhizoma atractylodis and 6-12g of lotus leaves. The traditional Chinese medicine composition regulates functions of spleen and kidney viscera by nourishing kidney, decreasing internal heat and invigorating spleen to eliminate dampness, and achieves the effects of reducing body weight and treating obesity and precocious puberty.

Description

Technical Field

[0001] The invention relates to the research field of Chinese medicine preparations, and in particular to a Chinese medicine compound composition for treating childhood obesity associated with precocious puberty. Background Art

[0002] Childhood obesity has a certain impact on the health of children and adults. Obesity can cause precocious puberty, metabolic problems and social and psychological problems (including depression and anxiety) in children. In recent years, the spectrum of childhood diseases has changed. More and more children have precocious puberty or early puberty, and metabolic and growth and development diseases have increased. Obesity is one of the important factors affecting precocious puberty in children, especially in female children. Because children's spleen is often insufficient, and children like to eat fatty, sweet and greasy food, and consume too much, the spleen loses its healthy function over time, and water and moisture accumulate. If the condensation does not disperse, it will turn into phlegm. Phlegm and dampness are diseases, and if they stay on the skin, it will be obesity. Most tonics are sweet and warm in nature, which can easily consume yin essence. In addition, due to the physiological characteristics of children's "constant kidney deficiency", children are prone to kidney yin deficiency, yin blood cannot control fire and moves recklessly, virtual fire disturbs the inside, the phase fire is hyperactive, and the kidney qi is too early, resulting in early arrival of Tiangui and precocious puberty. At present, the treatment of childhood obesity is still difficult, and there is no effective weight loss drug in childhood.

[0003] Ancient Chinese medicine did not have the name of obesity, but it had already discussed obesity, which can be traced back to the Spring and Autumn Period and the Warring States Period. "Lingshu Wei Qi Disorder" records three types of obesity syndromes: "fat people", "cream people" and "meat people". With the improvement of living standards, children eat too much fatty and greasy food, which is easy to produce phlegm and dampness, resulting in obesity. When phlegm and dampness accumulate in the milk network, it is milk plague; when phlegm and dampness block the network, the flow of qi and blood is not smooth, which hurts Chong and Ren. If Chong and Ren are out of balance, it will lead to early arrival of Tiangui. In addition, most tonic products are sweet and warm in nature, which can easily consume Yin essence. In addition, children's physiological characteristics of "kidney deficiency" are prone to kidney yin deficiency, Yin blood cannot control fire and moves recklessly, virtual fire disturbs the body, the phase fire is hyperactive, and the kidney qi is too early to be full, resulting in early arrival of Tiangui. "Breast plague" and "early arrival of Tiangui" are both manifestations of precocious puberty.

[0004] After searching, the Chinese patent with patent number CN 102579713 B improves childhood obesity by regulating phlegm and dampness caused by dysfunction of spleen and stomach. Currently, there is no Chinese herbal compound composition for treating childhood obesity with precocious puberty by strengthening the spleen and resolving phlegm, nourishing the kidney and reducing fire. Summary of the invention

[0005] In view of the above problems, the present invention aims to provide a Chinese medicine compound composition for treating childhood obesity and precocious puberty, which can regulate the spleen and kidney functions to enable the spleen and kidney functions to function normally.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] A traditional Chinese medicine compound composition for treating childhood obesity accompanied by precocious puberty, wherein the mass ratio of the components of the traditional Chinese medicine compound composition is as follows: Anemarrhena asphodeloides 9 - 15 g, Phellodendron amurense 9 - 15 g, Alisma orientale 15 - 20 g, Poria cocos 10 - 15 g, Citrus reticulata Blanco 6 - 12 g, Pinellia ternata (Thunb.) Breit. 6 - 12 g, Atractylodes lancea (Thunb.) DC. 10 - 20 g, and Nelumbo nucifera Gaertn. 6 - 12 g.

[0008] Preferably, the mass ratio of the components of the traditional Chinese medicine compound composition is as follows: Anemarrhena asphodeloides 9 g, Phellodendron amurense 9 g, Alisma orientale 15 g, Poria cocos 10 g, Citrus reticulata Blanco 6 g, Pinellia ternata (Thunb.) Breit. 6 g, Atractylodes lancea (Thunb.) DC. 10 g, and Nelumbo nucifera Gaertn. 6 g.

[0009] Preferably, the mass ratio of the components of the traditional Chinese medicine compound composition is as follows: Anemarrhena asphodeloides 15 g, Phellodendron amurense 15 g, Alisma orientale 20 g, Poria cocos 15 g, Citrus reticulata Blanco 12 g, Pinellia ternata (Thunb.) Breit. 12 g, Atractylodes lancea (Thunb.) DC. 20 g, and Nelumbo nucifera Gaertn. 12 g.

[0010] Preferably, the main components and the mass ratio of the traditional Chinese medicine compound composition are as follows: Anemarrhena asphodeloides 12 g, Phellodendron amurense 12 g, Alisma orientale 18 g, Poria cocos 12 g, Citrus reticulata Blanco 9 g, Pinellia ternata (Thunb.) Breit. 9 g, Atractylodes lancea (Thunb.) DC. 15 g, and Nelumbo nucifera Gaertn. 9 g.

[0011] The pharmacology of each raw material medicine is as follows:

[0012] Anemarrhena asphodeloides: Also known as Chimu, Lianmu, Wild Knotweed, Ground Ginseng. It is cold in nature and bitter in taste, and belongs to the lung meridian, stomach meridian, and kidney meridian. It has the effects of clearing heat and purging fire, nourishing yin and moistening dryness. It is used to treat vexation and thirst, consumptive fever, cough due to lung heat, dryness of the stool, and dysuria.

[0013] Phellodendron amurense: Also known as Sichuan Phellodendron. It is bitter in taste and cold in nature. It belongs to the kidney and bladder meridians. It has the effects of clearing away damp - heat and purging fire and detoxifying. Entering the kidney meridian to reduce ministerial fire, the ancients had the saying of strengthening kidney yin and removing deficiency heat. Therefore, it is an important medicine for the syndrome of internal heat due to deficiency caused by hyperactivity of ministerial fire, deficiency of kidney yin, and failure of water to control fire. It is mainly used to treat damp - heat diarrhea, jaundice with red urine, leukorrhea with genital itching, acute urinary tract infection with painful urination, beriberi with flaccidity, consumptive fever, night sweats, spermatorrhea, sores and boils, eczema and dermatitis.

[0014] Anemarrhena asphodeloides and Phellodendron amurense are quite commonly used pairs of heat - clearing (deficiency - heat - clearing) traditional Chinese medicines in clinical practice.

[0015] Alisma orientale: Also known as Shuize. It is sweet, light in taste and cold in nature, and belongs to the kidney and bladder meridians. It has the effects of promoting diuresis and percolating dampness, purging heat and reducing swelling, reducing turbidity and resolving fat. It is used for dysuria, edema, diarrhea with scanty urine, phlegm retention with dizziness, acute urinary tract infection with painful urination, hyperlipidemia.

[0016] Poria cocos: One of the widely used plants that can be used both as medicine and food. Also known as Futu, Songyu, Busi Mian, Songshu, Songmushu, Songling. It is sweet and flat in taste, and belongs to the heart, lung, spleen, and bladder meridians. It has the effects of promoting diuresis and percolating dampness, strengthening the spleen and calming the heart. It is mainly used to treat dysuria, edema, cough and counterflow due to phlegm retention, vomiting, poor appetite due to spleen deficiency, diarrhea, palpitation and restlessness, insomnia and amnesia, spermatorrhea and leukorrhagia.

[0017] Tangerine peel: Also known as orange peel, Guilao, red peel, yellow orange peel, Guang orange peel, Xinhui peel, tangerine peel, Guang tangerine peel. It tastes bitter and pungent, is warm in nature, and belongs to the lung and spleen meridians. It has the effects of regulating qi and strengthening the spleen, regulating the middle, drying dampness, and resolving phlegm. It is mainly used to treat abdominal distension or pain caused by spleen and stomach qi stagnation, indigestion, chest tightness and abdominal distension caused by dampness and turbidity blocking the middle, and loose stools due to poor appetite.

[0018] Processed Pinellia: Spicy, warm in nature, enters the spleen and lung meridians. It can both dry dampness and resolve phlegm, and harmonize the stomach and reduce adverse reactions. It is used for cough and asthma due to excessive phlegm, dizziness and palpitations caused by phlegm and fluid, dizziness caused by wind and phlegm, and headache caused by phlegm.

[0019] The 2020 edition of the Chinese Pharmacopoeia also has similar regulations for its use: Pinellia ternata is generally used after processing, 3 to 9 grams, and the raw product is mostly used externally. Chinese Pharmacopoeia Committee. Pharmacopoeia of the People's Republic of China 2020 Edition Volume 1 [S]. Beijing: China Medical Science and Technology Press, 2020: 123-125.

[0020] Processing can reduce the effect of calcium oxalate needle crystals, a toxic component of Pinellia ternata. Yuan Haijian, Jia Xiaobin, Yin Wenjing, et al. Analysis of research reports on the effects of processing on toxic components of Pinellia ternata and detoxification mechanisms [J]. Chinese Journal of Traditional Chinese Medicine, 2016, 41(23): 4462-4468

[0021] Pharmacological and toxicological studies have found that raw Pinellia ternata decoction, equivalent to a dose of 100 g / kg of raw medicine, is not toxic to mice (equivalent to 500 times the clinical dose), and processed Pinellia ternata does not show any toxicity. Yang Shouye, Ye Wenhua, Wu Zilun, et al. Study on the acute, subacute and cumulative toxicity of Pinellia ternata before and after processing on mice [J]. Chinese Patent Medicine, 1988(07):18-19.

[0022] Atractylodes: Also known as Xianshu, Xianjiang, Tianjing, Dikui, Maoshu, Qiangtoucai, Shancicai. It tastes pungent and bitter, and is warm in nature. It enters the spleen, stomach, and liver meridians. It has the effects of drying dampness and strengthening the spleen, dispelling wind and cold, and improving eyesight. It is mainly used to treat dampness blocking the middle jiao, abdominal distension, diarrhea, edema, beriberi, rheumatism, colds, night blindness, and blurred vision.

[0023] Lotus leaf: Another name is Qu. It tastes bitter, is neutral in nature, and belongs to the liver meridian, spleen meridian, and stomach meridian. It has the effects of clearing away heat and relieving summer heat, promoting the clear yang, and dispersing blood stasis and stopping bleeding. It is mainly used to treat summer heat and dampness, thirst, headache and dizziness, spleen deficiency and abdominal distension, diarrhea, blood in the leaves, and postpartum lochia.

[0024] Clinical Report

[0025] 1. Clinical data

[0026] Girls with obesity and precocious puberty who visited the Department of Pediatrics of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2022 to December 2023 were selected as research subjects.

[0027] This study used the body mass index (BMI) of obese children as the main outcome indicator. According to previous literature reports, it is estimated that the BMI of children in the treatment group can be reduced by about 3kg / m after 12 weeks of Chinese medicine combined with diet, exercise, and sleep intervention. 2 The control group of children can reduce their blood pressure by about 1-1.5 kg / m after 12 weeks of diet, exercise and sleep intervention. 2 , the difference in total effective rate between the two groups is between 20% and 30%. Assuming α = 0.05 (bilateral), β = 0.10. The sample size of the treatment group and the control group is calculated to be 38 cases in each group.

[0028] 2. Treatment options

[0029] 2.1 Treatment group: Chinese medicine combined with diet, exercise, and sleep intervention.

[0030] 2.2 Control group: diet, exercise, and sleep intervention.

[0031] Traditional Chinese medicine treatment: Anemarrhena asphodeloides 9g, Phellodendron chinense 9g, Alisma orientalis 15g, Poria 10g, Tangerine peel 6g, Processed Pinellia 6g, Lotus leaf 6g, Atractylodes lancea 10g.

[0032] After decocting the above medicines, take them twice a day, morning and evening, for 12 weeks.

[0033] Diet, exercise, and sleep intervention: Parents record their children's diet, exercise, and sleep

[0034] ①Dietary adjustment: It is recommended to control the total amount of food, adjust the dietary structure and dietary behavior. But do not use weight-loss foods and drinks that lack scientific basis. First of all, a balanced dietary structure is needed to ensure the needs of growth and development. The "Dietary Guidelines for Chinese Residents (2016)" recommends that each person consume more than 12 kinds of food per day and more than 25 kinds of food per week. When you are hungry between meals, give priority to foods with low energy density and strong satiety, such as low-fat dairy products, fresh fruits and vegetables, etc., while candies, cakes, beverages, etc. rich in refined sugar, as well as fried foods and puffed foods containing a lot of saturated fat and trans fat should be limited. In terms of dietary behavior, reduce fast food, dining out and ordering takeout; reduce high-fat, high-sodium, high-sugar or deeply processed foods; eating speed should not be too fast, and each meal time is recommended to be controlled within 20 to 30 minutes. Avoid watching electronic products while eating. The principles for matching various types of food can refer to the "Balanced Diet Pyramid" and "Balanced Diet Plate" designed in the "Dietary Guidelines for Chinese Residents 2016", which are divided into three categories: preferred (green light) food, restricted (yellow light) food and inappropriate (red light) food.

[0035] ② Appropriate physical activity: Various forms of physical activity suitable for age and personal ability should be carried out. According to the "Guidelines for Physical Activity for Children and Adolescents in China" published in 2017, it is recommended that healthy children aged 6 to 17 years old should accumulate at least 60 minutes of moderate and high-intensity physical activity every day, mainly aerobic exercise, at least 3 days of high-intensity physical activity per week, including resistance activity, and limit screen time to 2 hours per day. For obese children, it is recommended that on the basis of reaching the recommended amount for general children, within the scope of ability, gradually extend the time of each exercise, increase the frequency and intensity of exercise, reach aerobic exercise 3 to 5 times / week and resistance exercise 2 to 3 times / week, and form a habit of long-term exercise.

[0036] ③ Sleep intervention: Insufficient sleep is an important high-risk factor for childhood obesity and related metabolic diseases. Baseline sleep assessment of obese children is very important. If sleep disorders are found, intervention should be conducted on the child's sleep disorder first, and healthy sleep hygiene habits should be developed, such as a good sleep pattern and avoiding exciting activities before bedtime.

[0037] 2.3 Clinical efficacy assessment

[0038] Referring to the judgment principles of efficacy in "Traditional Chinese Medicine Clinical Research Ideas and Methods" edited by Ma Yingfeng and Xia Bo in 2019, combined with the trial drugs and treatment courses, and based on the opinions of pediatric experts:

[0039] The clinical efficacy of the two groups of children was divided into three indicators: markedly effective, effective, and ineffective.

[0040] Markedly effective: The weight of the child returned to normal level: BMI < 85% of children of the same age and gender, and the TCM symptom score decreased by ≥ 40%.

[0041] Effective: The child's weight is reduced to overweight level: BMI is 85% to 95% of the same age and gender. TCM symptom score is reduced by 10% ≤ <40%.

[0042] Ineffective: The child's weight is still at the obese level: BMI ≥ 95% of the same age and gender, and the TCM symptom score decreases by < 10%.

[0043] 3. Results

[0044] 3.1 Comparison of clinical efficacy between the two groups of children is shown in Table 1. Comparison of clinical efficacy between the two groups showed that the treatment group was significantly better than the control group (P < 0.05), as shown in Table 1.

[0045] Table 1 Comparison of weight loss between the two groups after treatment (%)

[0046]

[0047] Note: Total effective rate = (markedly effective + effective) / total number of cases × 100%.

[0048] 3.2 Comparison of TCM symptom scores between the two groups is shown in Table 2. There was no significant difference in the total scores of accompanying symptoms between the two groups before treatment; after treatment, the scores were improved compared with those before treatment (P < 0.05), and the improvement in the treatment group was better than that in the control group (P < 0.05).

[0049] Table 2 Comparison of TCM symptom scores before and after treatment (x±s)

[0050]

[0051] Note: Compared with the group before treatment, *P<0.05; compared with the control group after treatment, #P<0.05.

[0052] The beneficial effects of the present invention are:

[0053] The inventors explored the experience of traditional Chinese medicine treatment and combined it with clinical practice, and put forward the viewpoint of "regulating the spleen and kidney functions, reducing weight, and treating precocious puberty by nourishing the kidney and reducing fire, strengthening the spleen and removing dampness". According to this treatment principle, a Chinese medicine formula for treating the disease was formed, in which Phellodendron chinense and Rhizoma Anemarrhenae are the main herbs, and the two herbs are complementary to each other and are used to nourish yin and clear heat; processed Pinellia ternata, Poria cocos, Atractylodes macrocephala, and Tangerine peel are the assistant herbs to strengthen the spleen, dry dampness, and resolve phlegm; and Alisma orientalis and lotus leaf are the adjuvant herbs to clear heat and remove dampness. The whole formula nourishes yin and reduces fire, dries dampness, and eliminates turbidity. Clinically, it has been confirmed that this prescription can promote the improvement of spleen and kidney function, reduce weight, and treat precocious puberty. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below.

[0055] Figure 1 To observe the technical roadmap of the action mechanism of the Chinese herbal compound composition on obese precocious puberty mice;

[0056] Figure 2 This is a comparison chart between the obesity model group and the control group after rat modeling;

[0057] Figure 3 This is the ultrasound test report of the patient in Case 1 of Example 1 on August 7, 2022;

[0058] Figure 4 for Figure 3 The corresponding B-ultrasound image of the uterus;

[0059] Figure 5 for Figure 3 The corresponding patient’s ultrasound test report on June 1, 2024;

[0060] Figure 6 for Figure 5 The corresponding B-ultrasound image of the uterus;

[0061] Figure 7 This is the ultrasound test report of the patient in Case 2 of Example 1 on July 23, 2023;

[0062] Figure 8 for Figure 7 The corresponding B-ultrasound image of the uterus;

[0063] Fig. 9 for Figure 7 The corresponding patient’s ultrasound test report on May 19, 2024;

[0064] Fig.10 for Fig. 9 The corresponding B-ultrasound image of the uterus;

[0065] Fig.11 This is the ultrasound test report of the patient in Case 1 of Example 3 on June 29, 2022;

[0066] Fig.12 for Fig.11 The corresponding B-ultrasound image of the uterus;

[0067] Fig.13 for Fig.11 The corresponding patient’s ultrasound test report on December 18, 2022;

[0068] Fig.14 for Fig.13 The corresponding B-ultrasound image of the uterus;

[0069] Fig.15 This is the ultrasound test report of the patient in Case 2 of Example 3 on August 4, 2022;

[0070] Fig.16 for Fig.15 The corresponding B-ultrasound image of the uterus;

[0071] Fig.17 for Fig.15 The corresponding patient’s ultrasound test report on April 27, 2024;

[0072] Fig.18 for Fig.17 Corresponding B-ultrasound image of the uterus. DETAILED DESCRIPTION

[0073] In order to enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0074] In this application, according to the actual use of patients, the minimum dosage, common dosage and maximum dosage of the formula are developed, and three embodiments are used as examples.

[0075] Embodiment 1

[0076] A Chinese medicinal compound composition for treating childhood obesity and precocious puberty, wherein the formula comprises the following proportions by mass: 9g of Rhizoma Anemarrhenae, 9g of Cortex Phellodendri, 15g of Rhizoma Alismatis, 10g of Poria, 6g of Pericarpium Citri Reticulatae, 6g of Processed Pinellia, 10g of Atractylodes, and 6g of Lotus Leaf.

[0077] Embodiment 2

[0078] A Chinese medicinal compound composition for treating childhood obesity and precocious puberty, the formula comprising the following proportions by mass: 15g of Rhizoma Anemarrhenae, 15g of Cortex Phellodendri, 20g of Rhizoma Alismatis, 15g of Poria, 12g of Pericarpium Citri Reticulatae, 12g of Processed Pinellia, 12g of Lotus Leaf, and 20g of Atractylodes.

[0079] Embodiment 3

[0080] A Chinese medicinal compound composition for treating childhood obesity and precocious puberty, the formula comprising the following proportions by mass: 12g of Rhizoma Anemarrhenae, 12g of Cortex Phellodendri, 18g of Rhizoma Alismatis, 12g of Poria, 9g of Pericarpium Citri Reticulatae, 9g of Processed Pinellia, 15g of Rhizoma Atractylodis Macrocephalae, and 9g of Lotus Leaf.

[0081] Two typical cases for Example 1

[0082] Case 1

[0083] refer to Figure 3 to Figure 6 The patient, a female, 8 years and 5 months old, came to the pediatric outpatient clinic of our hospital on August 7, 2022 because of "overweight since childhood and bilateral breast enlargement for more than 6 months". The parents of the child said that the child has been overweight since childhood. More than 6 months ago, they found that the bilateral breasts were enlarged, and a hard lump could be touched. There was a slight swelling and pain, no redness, no pigmentation, and no secretion. There was no vaginal secretion. Denied a history of contact with nutritional supplements, cosmetics, etc. The height has increased by about 3cm in the past six months. Recently, the child has no fever, blurred vision, or headache. Physical examination: height 134cm (P50-P75), weight 35kg (P90-P97), BMI: 19.49kg / m 2 . (8.5-year-old girl BMI>18.1kg / m 2 Overweight, BMI>19.9kg / m 2 The patient was obese. No special facial features, well-proportioned body, breasts B2, vulva PH1, no vulva secretion. No milk coffee spots were found on the skin. Sex hormones: LH: 0.15IU / L, FSH: 2.05IU / L, E2: <40pmol / L, B-ultrasound: uterus size 22×17×15mm. Diagnosis: precocious puberty, overweight. After 6 months of treatment with this Chinese medicine prescription, the patient's height was 137cm, weight 34kg, BMI: 18.11kg / m 2 (9-year-old girl BMI>20.4kg / m 2The patient was obese. Physical examination: bilateral breast nuclei were not enlarged, vulva PH1, no secretion. He continued to take Chinese medicine until September 2023. Height: 142cm, weight: 38kg, BMI: 18.85kg / m 2 , bilateral breast stage B2, vulva stage PH1, stop taking Chinese medicine. Follow-up of the child in the outpatient clinic in June 2024, sex hormones: LH: 0.55IU / L, FSH: 5.05IU / L, E2: <40pmol / L re-examination. B-ultrasound: uterine size 27×13×6mm. Height 147cm, weight 41kg, BMI: 18.97kg / m 2 , bilateral breast stage B2, vulva stage PH1

[0084] Case 2

[0085] refer to Figure 7 to Figure 10 The patient, a 7-year-old girl, came to our outpatient clinic on July 23, 2023 because of "tenderness in the right breast for 2 weeks". The parents of the child found tenderness on the right side of the child 2 weeks ago, and a lump could be felt, without redness, pigmentation, or secretions. There is no vaginal secretion. The patient denied contact with nutritional supplements, cosmetics, etc. Height has increased by about 5cm in the past year. The child has no fever, blurred vision, or headache recently. Physical examination: height 132cm (P50-P75), weight 34kg (P90-P97), BMI: 19.5kg / m 2 . (8-year-old girl BMI>19.4kg / m 2 The patient was obese. No special facial features, well-proportioned body, right breast stage B2, left breast stage B1, vulva PH1, no vulva secretion. No milk coffee spots were found on the skin. Diagnosis: precocious puberty, obesity. After 3 months of treatment with this Chinese medicine prescription, the patient's height was 133cm, weight was 33kg, and BMI was 18.7kg / m 2 After taking this prescription for 3 months, the patient's height is 135cm, weight is 33kg, and BMI is 18.1kg / m 2 . The breast nodules disappeared, the vulva pH was 1, and there was no discharge.

[0086] Two typical cases for Example 2

[0087] Case 1

[0088] The patient, a 9-year-old boy, came to the outpatient clinic on April 24, 2021 due to "rapid weight gain for more than 5 years". The patient's parents reported that the child gained weight too fast after the age of 4, but the details were unknown and they did not take it seriously. He denied taking any nutritional supplements or medications. He has grown about 3-4cm in height in the past six months. The child has no fever, blurred vision, or headache recently. He has a good appetite, sleeps well at night, and has dry stools, one every 2-3 days. Physical examination: height 142cm (P90-P97), weight 56kg (>P97), BMI: 27.77kg / m 2(9.5-year-old boy BMI>21.4kg / m 2 The patient was obese. The patient was conscious and had good mental response. There was acanthosis nigricans on the neck (+). The thyroid gland was not palpable. Auscultation of the heart and lungs was (-). The abdomen was soft. The liver and spleen were not enlarged. NS (-). The testicles were 8ml on both sides. The vulva was PH1. The tongue was red with yellow greasy coating and the pulse was slippery. Auxiliary examinations: liver function: ALT55U / L, AST51U / L, blood lipids: TC4.01mmol / L, TG0.76mmol / L. Ultrasound: fatty liver. Diagnosis: metabolic-related fatty liver and precocious puberty. The patient was treated with this prescription for 2 years. The BMI of the child was 23.74kg / m 2 , liver function is normal. Sexual development and bone age are within the age range of children. B-ultrasound: no obvious abnormalities were found in liver, gallbladder, pancreas, spleen and kidney.

[0089] Case 2

[0090] The patient, a boy, aged 11 years and 6 months, came to the outpatient clinic on July 24, 2023 because of "rapid weight gain for more than 3 years and voice change for 1 month". The patient's parents reported that the child gained weight rapidly 3 years ago and did not pay attention to it. Voice change occurred 1 month ago, and he denied taking nutritional supplements, drugs, etc. He has grown about 5cm in the past six months. The child has no blurred vision or headache. He has a good appetite, sleeps well at night, and has dry stool once a day. Physical examination: height 152cm (P50-P75), weight 62kg (>P97), BMI: 26.8 / m 2 (11.5-year-old boy BMI>23.6kg / m 2 The child was obese). Conscious, mental response was good, neck acanthosis (+), thyroid not palpable, heart and lung auscultation (-), abdomen soft, liver and spleen not enlarged, NS (-). Bilateral testicles 20ml, vulva PH3 stage. Red tongue with thin yellow greasy coating, slippery pulse. Auxiliary examination: bone age 13.5 years old, sex hormones: LH: 3.35IU / L, FSH: 8.05IU / L, liver function, blood lipids: normal. Diagnosis: precocious puberty, obesity. The child was treated with dapoxetine combined with this prescription for 1.5 years, and the child's BMI: 23.3kg / m 2 , bone age 14 years+.

[0091] Two typical cases for Example 3

[0092] Case 1

[0093] refer to Figure 11 to Figure 14The patient, a female, 8 years and 9 months old, came to the outpatient clinic on June 29, 2022 because of "breast development for half a year and rapid weight gain for more than 2 years". The parents of the child complained that the child gained weight too fast 2 years ago and did not pay attention to it. Denied the history of taking nutritional supplements, drugs, etc. In the past six months, the child's breasts have increased significantly, there is no secretion from the vulva, and the height has increased by 4cm in the past six months. The child has no blurred vision and no headache. Good appetite, late sleep time, difficulty falling asleep, and dry stool once a day. Physical examination: height 140cm (P75-P90), weight 40kg (>P97), BMI: 20.4kg / m 2 (8.5-year-old girl BMI>19.9kg / m 2 The child was obese). Conscious, mental response was good, acanthosis nigricans on the neck (-), thyroid not palpable, heart and lung auscultation (-), abdomen soft, liver and spleen not enlarged, NS (-). Bilateral breasts were B3, vulva was PH1. Tongue red with yellow greasy coating, pulse slippery. Auxiliary examination: sex hormones: LH: 0.35IU / L, FSH: 1.05IU / L, E2: <40pmol / L, liver function, blood lipids: normal. B-ultrasound: uterus size 26×19×28mm. Diagnosis: precocious puberty, obesity. After 6 months of treatment with this prescription, the child was 143cm tall, weighed 37kg, and had a BMI of 18.1kg / m 2 , liver function is normal, reexamination of uterine appendages B-ultrasound, uterus no significant enlargement compared with six months ago. Physical examination: bilateral breast B3 stage, vulva PH1 stage. Continue Chinese medicine treatment until now, menstruation has not come.

[0094] Case 2

[0095] refer to Figure 15 to Figure 18 The patient is a female, 8 years and 11 months old. She came to the outpatient clinic on August 4, 2022 because of "rapid weight gain for more than 3 years and menstruation for 1 month". The parents of the child reported that the child gained weight too fast more than 3 years ago and did not pay attention to it. On June 25, 2022, she had her first menstruation, with a small amount of brown color, for 2 consecutive days. She denied taking any nutritional supplements or drugs. She has grown 10cm in height in the past year. The child has no blurred vision or headache. She has a good appetite, sleeps well at night, and has bowel movements every 2-3 days. Physical examination: height 152cm (=P97), weight 56kg (>P97), BMI 24.2kg / m 2 (10-year-old girl BMI>21.5kg / m 2The patient was obese). Conscious, mental response was good, acanthosis nigricans on the neck (-), thyroid gland not palpable, heart and lung auscultation (-), abdomen soft, liver and spleen not enlarged, NS (-). Bilateral breasts were stage B4, and vulva was stage PH3. The tongue was red with yellow greasy coating, and the pulse was stringy and slippery. Auxiliary examination: sex hormones: LH: 4.35IU / L, FSH: 7.05IU / L, E2: 98pmol / L, PRL: 99.46mIU / L. AFP, β-HCG: normal. Liver function, blood lipids: normal. B-ultrasound: uterus size 37×20×28mm, endometrium 2.5mm. Pituitary MRI enhancement: pituitary enlargement. Diagnosis: precocious puberty, obesity. The patient was treated with dafilin combined with this prescription until April 27, 2024. The child was 157cm tall, weighed 50kg, and had a BMI of 20.28kg / m 2 , menstruation has not come. Re-examination of sex hormones: LH: 1.35IU / L, FSH: 2.05IU / L, E2: <40pmol / L, B-ultrasound: uterus size 28×16×27mm, endometrium 1mm.

[0096] Observation of the mechanism of action of a Chinese herbal compound on obese precocious puberty in young mice

[0097] 1. Preparation of Obese Precocious Puberty Mouse Model

[0098] according to Figure 1 Technical route: Model preparation, 12 female and 6 male 9-week-old SPF SD rats (all provided by Beijing Weitong Lihua Company). Animals were free to drink water and eat, and the SPF environment in the barrier was standard. After one week of adaptive feeding, the rats were mated at a ratio of ♀:♂ of 2:1. The male rats were removed at 14 days of age, and the number of pups per litter was adjusted to 6. They were weaned at 21 days of age. According to the completely random grouping, they were divided into a model group (mixed feeding for 2 weeks and high-fat feeding for 6 weeks) and a control group (ordinary feeding). The modeling time was 8 weeks. Basic feed: standard feed provided by the animal room, produced and provided by Jiangsu Collaborative Biotechnology Co., Ltd. High-fat feed: 30% fat content, 20% protein, 50% carbohydrates, produced and provided by Jiangsu Collaborative Biotechnology Co., Ltd. When the rats were 11 weeks old (8 weeks after modeling), the model group screened out individuals whose body weight was greater than 20% of the control group and whose vulva opening time was earlier than the average opening time of the control group, and set them as the "obese precocious group".

[0099] 2. Drug administration

[0100] The obese model rats were randomly divided into three groups, namely, the high-dose Chinese medicine group,

[0101] The rats in the high-dose group were gavaged with a concentration of 10.08 mg / g, the rats in the low-dose group were gavaged with 2.52 mg / g, and the rats in the model group and the control group were gavaged with normal saline. The gavage volume was 1 ml / rat / 100 g, once a day. After four weeks of gavage, the body weight, total cholesterol, serum triglycerides, luteinizing hormone, follicle-stimulating hormone, and estradiol were measured in each group.

[0102] 3. Results

[0103] 3.1 Body weight changes of rats

[0104] When the rats were 11 weeks old (8 weeks after modeling), the model group was selected to select individuals with a body mass 20% higher than that of the control group as the obesity model group, and the obesity model group was compared with the control group. Figure 2 .

[0105] There was a significant statistical difference in the body weight of the two groups of rats, P = 0.01; the body weight of the rats in the obesity model group was significantly higher than that in the control group (see Table 1).

[0106] Table 1. Comparison of body weight between rats in the 11-week-old obesity model group and the control group (g)

[0107]

[0108] Since the data do not conform to a normal distribution, the median is used.

[0109] 3.2 Comparison of vulva opening time in rats

[0110] There was a very significant statistical difference in the vulva opening time between the control group and the obesity model group, P<0.01; the vulva opening time of the obesity model group rats was earlier than that of the control group rats (see Table 2)

[0111] Table 2. Comparison of vulvar opening time between the obesity model group and the control group (days)

[0112]

[0113] Since the data are not normally distributed, the median is used.

[0114] **P<0.01, indicating a significant statistical difference

[0115] 3.3 Changes of TC in rats in each group before and after treatment

[0116] The TC value of the high-dose group after administration was significantly lower than that before administration (P<0.01); there was no significant statistical difference in TC value before and after administration in the low-dose group (P>0.05); the TC value of the control group before and after administration was lower than that before administration (P<0.05); there was no significant statistical difference in TC value of the model group before and after administration (P>0.05) (see Table 3).

[0117] Table 3. Comparison of TC in rats in the control group, model group, high-dose group, and low-dose group before and after administration (mmol / L)

[0118]

[0119] *P<0.05, indicating a significant statistical difference

[0120] 3.4 Comparison of TG changes in rats in each group before and after administration

[0121] The TG value of the high-dose group after administration was lower than that before administration (P<0.05); there was no significant statistical difference in TG value before and after administration in the low-dose group (P>0.05); the TG value of the control group before administration was lower than that after administration (P<0.05); there was no significant statistical difference in TC value before and after administration in the model group (P>0.05) (see Table 4).

[0122] Table 4. Comparison of TG in rats in the control group, model group, high-dose group, and low-dose group before and after administration (mmol / L)

[0123]

[0124] a. Because the data does not conform to the normal distribution, the rank sum test is used, Z = -2.497

[0125] 3.5 Comparison of sex hormones in rats in each group before and after administration

[0126] There was no statistical difference in serum LH, FSH, and E2 among the four groups of rats (P>0.05); however, the levels of serum LH, FSH, and E2 in the Chinese medicine group were lower than those in the model group and the control group, indicating that the administration of the drug had a certain inhibitory effect on the sex hormones of the rats. However, due to the rapid development and maturation cycle of rats, the rats had reached adulthood after the administration of the drug, and the changes in the sex hormone levels of puberty could not be observed (see Table 5).

[0127] Table 5. Comparison of FSH, LH and E2 in 4 groups of rats after administration

[0128]

[0129] FSH data do not follow a normal distribution, so the median is used to describe

[0130] This experiment confirmed that this Chinese medicine formula can control body weight, inhibit sex hormones, and prevent the occurrence of precocious puberty.

[0131] The above shows and describes the basic principles, main features and advantages of the present invention. It should be understood by those skilled in the art that the present invention is not limited to the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention to be protected. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A Chinese medicinal compound composition for treating childhood obesity and precocious puberty, characterized in that: The weight proportion is as follows: Rhizoma Anemarrhenae 9-15g, Cortex Phellodendri 9-15g, Rhizoma Alismatis 15-20g, Poria 10-15g, Pericarpium Citri Reticulatae 6-12g, Processed Pinellia 6-12g, Rhizoma Atractylodis Macrocephalae 10-20g, and Lotus Leaf 6-12g.

2. A Chinese medicinal compound composition for treating childhood obesity and precocious puberty according to claim 1, characterized in that: The mass proportion is: 9g of Anemarrhena asphodeloides, 9g of Phellodendron chinense, 15g of Alisma orientalis, 10g of Poria, 6g of Citrus reticulatae, 6g of processed Pinellia ternata, 10g of Atractylodes lancea, and 6g of Lotus leaf.

3. A Chinese medicinal compound composition for treating childhood obesity and precocious puberty according to claim 1, characterized in that: The mass proportion is: 15g of Anemarrhena asphodeloides, 15g of Phellodendron chinense, 20g of Alisma orientalis, 15g of Poria, 12g of Citrus reticulatae, 12g of processed Pinellia ternata, 20g of Atractylodes lancea, and 12g of Lotus leaf.

4. A Chinese medicinal compound composition for treating childhood obesity and precocious puberty according to claim 1, characterized in that: The mass proportion is: 12g of Anemarrhena asphodeloides, 12g of Phellodendron chinense, 18g of Alisma orientalis, 12g of Poria, 9g of Citrus reticulatae, 9g of processed Pinellia ternata, 15g of Atractylodes lancea, and 9g of Lotus leaf.

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