A traditional Chinese medicine composition for improving insulin secretion pattern disorder in obese patients

Abstract

This invention belongs to the field of traditional Chinese medicine (TCM) technology, specifically relating to a TCM composition for improving insulin secretion pattern disorders in obese patients. Targeting the core pathogenesis of phlegm-heat stagnation in obese individuals, this invention provides a TCM composition with the therapeutic principles of clearing the lungs and resolving phlegm, regulating qi and bowel movements, clearing heat and promoting blood circulation, and eliminating turbidity and regulating the body's balance. The composition consists of mulberry bark, platycodon root, pinellia tuber, trichosanthes fruit, acorus tatarinowii rhizome, magnolia bark, immature bitter orange, coptis root, salvia root, euonymus root, clematis root, and smilax rhizome. This TCM composition can simultaneously improve blood lipid indicators such as total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein, comprehensively correcting obesity-related lipid disorders, blocking lipotoxic damage to the pancreas, and comprehensively improving systemic metabolic disorders caused by phlegm-heat stagnation. Furthermore, the formula is simple, the medicinal materials are commonly used and readily available, and it can be directly decocted and taken clinically, making it widely applicable.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for improving insulin secretion pattern disorders in obese patients. Background Technology

[0002] Obesity is a complex chronic metabolic disease, primarily defined based on body mass index (BMI), which is weight (kg) divided by the square of height (m). The WHO defines a BMI ≥ 30 kg / m² as... 2 Defined as obese, 25-29.9 kg / m² 2 Defined as overweight. Obesity is a major public health problem in my country, with a large number of overweight and obese individuals. Data shows that over 70% of obese patients have abnormal insulin secretion patterns, typically manifested as elevated fasting insulin levels, insufficient early-phase insulin secretion in oral glucose tolerance tests, and significant postprandial blood glucose fluctuations. This pathological change is a core driving factor in the development of insulin resistance, type 2 diabetes, metabolic syndrome, and obstructive sleep apnea. Insulin resistance, as a core pathological feature of obesity-related metabolic disorders, is mainly characterized by decreased sensitivity to insulin. Clinical data shows that approximately 75% of obese patients have insulin resistance, and this metabolic abnormality significantly increases the risk of chronic diseases such as type 2 diabetes and cardiovascular disease.

[0003] Currently, interventions for obesity combined with abnormal insulin secretion fall into three categories: Western medicine, simple dietary restriction, and traditional Chinese medicine compound prescriptions. Among Western medicine interventions: metformin primarily improves insulin resistance and reduces hepatic glucose output; SGLT-2 inhibitors mainly lower blood sugar through urinary glucose excretion, but both have limited effects on restoring the secretory rhythm of pancreatic β-cells; injectable GLP-1 receptor agonists, while promoting glucose-dependent insulin secretion, only regulate through a single pathway and cannot simultaneously address the multiple complex damages caused by glucose, lipid, and uric acid metabolism, as well as obesity combined with snoring, making it difficult to comprehensively correct the overall disordered insulin secretion pattern in obese individuals; simple time-restricted diets easily induce hunger and fatigue, making them difficult to maintain long-term. In simple dietary restriction interventions, for obese patients, replacing refined carbohydrates with low-sugar whole grains and following the "vegetables-protein-staple food" meal order can delay sugar absorption and reduce the burden, but it only treats the symptoms, not the root cause; improper combination or long-term excessive restriction of carbohydrate intake can easily lead to metabolic fluctuations, indirectly increasing the burden on the pancreas. Among the traditional Chinese medicine compound intervention methods, most of the existing traditional Chinese medicine compound prescriptions for treating obesity and glucose metabolism disorders only focus on weight loss or blood sugar reduction on one side, and rarely take into account obesity combined with snoring and high uric acid combined with metabolic damage, and rarely directly address the core pathogenesis of "phlegm-heat stagnation".

[0004] Therefore, existing intervention methods all have certain shortcomings. Currently, there is a lack of traditional Chinese medicine compositions that can target and improve insulin secretion pattern disorders, simultaneously regulate glucose, lipids, and uric acid, alleviate obesity and snoring symptoms, and have high overall safety in clinical practice. There is an urgent clinical need for such a combination. Summary of the Invention

[0005] This invention addresses the core pathogenesis of phlegm-heat stagnation in obese individuals, providing a traditional Chinese medicine composition that utilizes the principles of clearing the lungs and resolving phlegm, regulating qi and relieving constipation, clearing heat and promoting blood circulation, and eliminating turbidity and regulating the body's balance. This composition effectively improves systemic metabolic disorders caused by phlegm-heat stagnation. Based on this, the invention was completed.

[0006] In a first aspect, the present invention provides a traditional Chinese medicine composition for improving insulin secretion pattern disorders in obese patients. The traditional Chinese medicine composition consists of the following traditional Chinese medicines in parts by weight: 20-50 parts of mulberry bark, 10-25 parts of platycodon root, 5-20 parts of pinellia tuber, 5-20 parts of trichosanthes fruit, 20-50 parts of acorus tatarinowii rhizome, 5-20 parts of magnolia bark, 5-20 parts of immature bitter orange, 1-5 parts of coptis root, 20-50 parts of salvia root, 5-20 parts of euonymus alatus root, 5-20 parts of clematis root, and 10-25 parts of smilax glabra rhizome.

[0007] Furthermore, the traditional Chinese medicine composition comprises the following traditional Chinese medicines in parts by weight: 25-40 parts of mulberry bark, 15-20 parts of platycodon root, 10-15 parts of pinellia tuber, 10-15 parts of trichosanthes fruit, 25-40 parts of acorus tatarinowii rhizome, 10-15 parts of magnolia bark, 10-15 parts of immature bitter orange, 2-4 parts of coptis root, 25-40 parts of salvia miltiorrhiza root, 10-15 parts of euonymus alatus root, 10-15 parts of clematis root, and 15-20 parts of smilax glabra rhizome.

[0008] Furthermore, the traditional Chinese medicine composition consists of the following traditional Chinese medicines in parts by weight: 30 parts of mulberry bark, 18 parts of platycodon root, 12 parts of pinellia tuber, 12 parts of trichosanthes fruit, 30 parts of acorus tatarinowii rhizome, 12 parts of magnolia bark, 12 parts of immature bitter orange, 3 parts of coptis root, 30 parts of salvia miltiorrhiza root, 12 parts of euonymus alatus root, 12 parts of clematis root, and 18 parts of smilax glabra rhizome.

[0009] Furthermore, the aforementioned insulin secretion pattern disorder is characterized by the pancreas' inability to precisely match changes in blood glucose levels with insulin secretion, resulting in decreased cellular sensitivity to insulin and excessive pancreatic insulin secretion. In the long term, this may lead to functional failure, with clinical manifestations mainly including blood glucose fluctuations, weight changes, fatigue, and increased hunger.

[0010] Furthermore, the disordered insulin secretion pattern in the obese patients is diagnosed as phlegm-heat stagnation syndrome in Traditional Chinese Medicine.

[0011] In a second aspect, the present invention provides a traditional Chinese medicine preparation made from the traditional Chinese medicine composition for improving insulin secretion pattern disorder in obese patients as described in the first aspect, wherein the traditional Chinese medicine composition consists of the following traditional Chinese medicines in parts by weight: 20-50 parts of mulberry bark, 10-25 parts of platycodon root, 5-20 parts of pinellia tuber, 5-20 parts of trichosanthes fruit, 20-50 parts of acorus tatarinowii rhizome, 5-20 parts of magnolia bark, 5-20 parts of immature bitter orange, 1-5 parts of coptis root, 20-50 parts of salvia miltiorrhiza root, 5-20 parts of euonymus alatus root, 5-20 parts of clematis root, and 10-25 parts of smilax glabra rhizome.

[0012] Furthermore, the traditional Chinese medicine preparation is selected from one of the following: ointment, oral liquid, decoction, granule, capsule or tablet.

[0013] Furthermore, the traditional Chinese medicine preparation contains pharmaceutically acceptable excipients.

[0014] Furthermore, the pharmaceutically acceptable excipients are pharmaceutical excipients that enhance the efficacy of the active pharmaceutical ingredient, reduce its toxicity, and / or alleviate its side effects.

[0015] Furthermore, the aforementioned insulin secretion pattern disorder is characterized by the pancreas' inability to precisely match changes in blood glucose levels with insulin secretion, resulting in decreased cellular sensitivity to insulin and excessive pancreatic insulin secretion. In the long term, this may lead to functional failure, with clinical manifestations mainly including blood glucose fluctuations, weight changes, fatigue, and increased hunger.

[0016] Furthermore, the disordered insulin secretion pattern in the obese patients is diagnosed as phlegm-heat stagnation syndrome in Traditional Chinese Medicine.

[0017] Thirdly, the present invention provides the use of the traditional Chinese medicine composition described in the first aspect in the preparation of a medicament for improving insulin secretion pattern disorders in obese patients.

[0018] Furthermore, the aforementioned insulin secretion pattern disorder is characterized by the pancreas' inability to precisely match changes in blood glucose levels with insulin secretion, resulting in decreased cellular sensitivity to insulin and excessive pancreatic insulin secretion. In the long term, this may lead to functional failure, with clinical manifestations mainly including blood glucose fluctuations, weight changes, fatigue, and increased hunger.

[0019] Furthermore, the disordered insulin secretion pattern in the obese patients is diagnosed as phlegm-heat stagnation syndrome in Traditional Chinese Medicine.

[0020] The medicinal properties and effects of each Chinese medicinal herb in this invention are as follows: Mulberry bark: Sweet, cold. Enters the Lung meridian. Clears lung heat and relieves asthma, promotes diuresis and reduces swelling. Used for cough and asthma due to lung heat, edema with abdominal distension and scanty urine, and facial and skin edema.

[0021] Platycodon grandiflorus: Bitter, pungent, neutral. Enters the Lung meridian. Clears the lungs, soothes the throat, eliminates phlegm, and drains pus. Used for cough with excessive phlegm, chest tightness, sore throat and hoarseness, and lung abscess with purulent sputum.

[0022] Pinellia ternata: pungent, warm; toxic. Enters the spleen, stomach, and lung meridians. It dries dampness and resolves phlegm, relieves nausea and vomiting, and dissipates lumps and nodules. Used for damp phlegm, cold phlegm, cough with excessive phlegm, phlegm-dampness causing dizziness and palpitations, wind-phlegm causing dizziness, phlegm-induced headache, vomiting and nausea, chest and epigastric fullness, and globus hystericus; externally used to treat carbuncles and phlegm nodules.

[0023] Trichosanthes kirilowii: Sweet, slightly bitter, cold. It enters the lung, stomach, and large intestine meridians. It clears heat and resolves phlegm, relieves chest congestion and dissipates nodules, moistens dryness and lubricates the intestines. It is used for cough due to lung heat, thick yellow phlegm, chest pain, chest tightness and fullness, mastitis, lung abscess, intestinal abscess, and constipation.

[0024] 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 the appetite. It is used for coma, epilepsy, forgetfulness, insomnia, tinnitus, deafness, epigastric fullness and lack of appetite, and dysentery with aversion to food.

[0025] Magnolia officinalis: Bitter, pungent, and warm. It enters the spleen, stomach, lung, and large intestine meridians. It dries dampness and resolves phlegm, lowers qi and relieves fullness. It is used for dampness stagnation in the middle jiao, epigastric fullness and vomiting / diarrhea, food stagnation and qi stagnation, abdominal distension and constipation, and phlegm-dampness cough and wheezing.

[0026] Fructus Aurantii Immaturus: Bitter, pungent, sour, slightly cold. Enters the spleen and stomach meridians. It breaks up stagnation and eliminates accumulations, resolves phlegm and disperses masses. Used for internal stagnation, abdominal distension and pain, tenesmus after diarrhea, constipation, phlegm stagnation and qi obstruction, chest pain, chest tightness, and organ prolapse.

[0027] Coptis chinensis: Bitter, cold. It enters the heart, spleen, stomach, liver, gallbladder, and large intestine meridians. It clears heat and dries dampness, drains fire and detoxifies. Used for damp-heat fullness, vomiting and acid regurgitation, diarrhea, jaundice, high fever with delirium, excessive heart fire, restlessness and insomnia, palpitations, hematemesis due to blood heat, red eyes, toothache, thirst, carbuncles and boils; externally used for eczema, damp sores, and ear discharge. Wine-processed Coptis chinensis effectively clears heat from the upper burner. Used for red eyes and mouth sores. Ginger-processed Coptis chinensis clears and harmonizes the stomach and stops vomiting. Used for alternating chills and fever, damp-heat obstruction, fullness, and vomiting. Cornus-processed Coptis chinensis soothes the liver, harmonizes the stomach, and stops vomiting. Used for liver-stomach disharmony, vomiting and acid regurgitation.

[0028] Salvia miltiorrhiza: Bitter, slightly cold. It enters the heart and liver meridians. It invigorates blood circulation and removes blood stasis, regulates menstruation and relieves pain, clears the heart and eliminates irritability, cools the blood and reduces swelling. It is used for chest pain, abdominal and hypochondriac pain, abdominal masses, painful arthralgia due to heat, insomnia due to irritability, irregular menstruation, dysmenorrhea, amenorrhea, and sores and swelling.

[0029] Euonymus alatus: Bitter, pungent, cold, enters the liver meridian. Used to invigorate blood circulation, regulate menstruation, disperse blood stasis, relieve pain, detoxify, and reduce swelling.

[0030] Clematis chinensis: pungent, salty, and warm. It enters the bladder meridian. It dispels wind and dampness, and unblocks the meridians. It is used for rheumatic pain, numbness of limbs, muscle contractures, and difficulty in flexion and extension.

[0031] Smilax glabra: Sweet, bland, and neutral in nature. It enters the liver and stomach meridians. It detoxifies, eliminates dampness, and promotes joint mobility. It is used for limb contractures and muscle and bone pain caused by syphilis and mercury poisoning; damp-heat urinary tract infections, leukorrhea, carbuncles, scrofula, and scabies.

[0032] The formulation and treatment principles of this invention Targeting the core pathogenesis of phlegm-heat stagnation in obese individuals, this invention provides a traditional Chinese medicine composition with the therapeutic principles of clearing the lungs and resolving phlegm, regulating qi and relieving constipation, clearing heat and promoting blood circulation, and eliminating turbidity and regulating the body's balance. This composition uses mulberry bark and platycodon root as the principal herbs. Mulberry bark is sweet and cold in nature, enters the lung meridian, clears lung heat and promotes urination, clears phlegm-heat in the upper burner, unblocks the lung's water passages, reduces visceral and airway fat edema, and blocks the source of phlegm formation. Platycodon root is bitter, pungent, and neutral in nature, clears the lungs, benefits the throat, carries the medicine upwards, and restores the lung's function of regulating water passages. The two herbs, one clearing and one descending, unblock the upper source of the three burners, improve obese snoring, and eliminate the pathological basis of phlegm-heat stagnation interfering with pancreatic secretion. Pinellia ternata is pungent and warm, drying dampness, resolving phlegm, eliminating lumps and harmonizing the stomach, and clearing phlegm and dampness in the middle jiao; Trichosanthes kirilowii is sweet and cold, clearing heat, eliminating phlegm, relieving chest congestion, and resolving phlegm and heat in the triple jiao; Acorus tatarinowii is aromatic and opens the orifices, clearing phlegm and turbidity in the nasal and pharyngeal meridians, resolving phlegm and heat stagnation, and improving metabolic disorders caused by qi stagnation; Magnolia officinalis is bitter and warm, promoting qi circulation, relieving bloating, drying dampness, and eliminating fullness, and alleviating abdominal distension in obese people; Citrus aurantium breaks up qi stagnation, clears the bowels and descends turbidity, promoting the excretion of lipids and metabolic toxins from the intestines, reducing the pressure of visceral fat on the pancreas. The above five herbs differentiate phlegm and promote qi circulation, clear the middle jiao, clear the bowels, and dissipate phlegm and heat stagnation throughout the body, assisting the principal herb as the assistant herb; Small doses of Coptis chinensis, bitter and cold in nature, clear heat and dry dampness, directly clear damp-heat in the middle jiao, reduce excessive absorption of sugar in the intestines, enhance insulin sensitivity, and resolve the source of phlegm-heat; Salvia miltiorrhiza invigorates blood and cools blood, unblocks the microcirculation throughout the body, and improves pancreatic blood supply; Euonymus alatus invigorates blood and unblocks collaterals, protects pancreatic β cells, dissipates blood stasis, and restores the rhythm of insulin secretion; Clematis chinensis dispels wind and dampness, and unblocks the meridians and eliminates turbid toxins; Smilax glabra clears heat and promotes diuresis, lowers blood uric acid levels, and reduces the damage to pancreatic function caused by chronic inflammation secondary to phlegm-heat stasis.

[0033] The formula contains mulberry bark, coptis, and trichosanthes fruit, which are slightly cold and clear away phlegm and heat. Pinellia, magnolia bark, and acorus are warm and promote the flow of phlegm and dissipate nodules, thus balancing the cold and heat. The combined effects of these herbs promote the flow of qi in the upper, middle, and lower parts of the body, dissipate phlegm and heat stagnation in the three jiaos, repair the secretory function of pancreatic β cells, and simultaneously regulate the levels of blood lipids, uric acid, and blood sugar.

[0034] The formula comprehensively promotes lung function, resolves phlegm, regulates qi and bowels, clears heat and invigorates blood, eliminates turbidity and regulates the body's balance, dissipates phlegm-heat stagnation, reverses abnormal insulin secretion patterns in obese patients, simultaneously reduces weight and fat, improves sleep and snoring, and comprehensively regulates blood lipid and uric acid metabolism disorders.

[0035] Beneficial effects 1. Precisely targets the pathogenesis and can systematically reverse abnormal insulin secretion patterns. This invention's traditional Chinese medicine composition closely addresses the core pathogenesis of phlegm-heat stagnation and blood stasis, going beyond single-point insulin values. It uses a complete secretion curve from an oral glucose tolerance test (OGTT) for quantitative evaluation: effectively reducing fasting compensatory hyperinsulinemia, restoring peak insulin shift time and peak insulin secretion amplitude, and improving early-phase secretion deficiency; combined with C-peptide correction of hepatic insulin extraction rate, it calculates the area under the curve (AUC) for early-phase and all-day insulin secretion, comprehensively repairing the rhythmic secretion function of pancreatic β-cells, and fundamentally correcting the abnormal insulin secretion pattern (AISP).

[0036] 2. Comprehensively regulates lipid metabolism, covering a full range of blood lipid indicators. The herbal composition of this invention can simultaneously improve four blood lipid indicators: total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein, comprehensively correct obesity-related blood lipid disorders, and block lipid toxicity damage to the pancreas.

[0037] 3. Simultaneous improvement of complex metabolic complications through multiple targets This invention provides a single compound formula that addresses multiple issues including obesity, snoring, hyperlipidemia, hyperuricemia, and insulin resistance, without requiring the combined use of multiple Chinese and Western medicines. It comprehensively improves systemic metabolic disorders caused by phlegm-heat stagnation.

[0038] 4. The medicine has mild properties and is highly safe for long-term use. The dosage of Coptis chinensis in the herbal composition of this invention is controlled to avoid damage to the spleen due to its bitter and cold nature, while the blood-activating herbs are mild and do not deplete qi. The incidence of adverse reactions in clinical trials is extremely low, with only mild abdominal distension observed, which can be relieved spontaneously after 3 days without needing to stop the medication, making it suitable for long-term intervention.

[0039] 5. The medicinal materials are readily available, making clinical application convenient. The herbal composition of this invention consists of all commonly used Chinese medicinal materials in clinical practice, with no rare raw materials. It can be used to prepare various oral preparations such as decoctions, granules, and capsules, and can be widely used in primary clinics and community hospitals. Detailed Implementation

[0040] The specific embodiments of the present invention will be further described below. It should be noted that these descriptions are for the purpose of aiding understanding the present invention, but do not constitute a limitation thereof. Furthermore, the technical features involved in the embodiments described below can be combined with each other as long as they do not conflict with each other.

[0041] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods, and the experimental materials used in the following embodiments are all available through conventional commercial channels.

[0042] Example 1: Preparation of the traditional Chinese medicine preparation of the present invention The herbal composition consists of: 30 g of mulberry bark, 18 g of platycodon root, 12 g of pinellia tuber, 12 g of trichosanthes fruit, 30 g of acorus tatarinowii rhizome, 12 g of magnolia bark, 12 g of immature bitter orange, 3 g of coptis root, 30 g of salvia root, 12 g of euonymus alatus root, 12 g of clematis root, and 18 g of smilax glabra rhizome.

[0043] Preparation process: The first step is to weigh the Chinese herbs according to the above ingredients and proportions, remove impurities, wash them, drain the water, and set them aside. The second step is to mix the Chinese herbs processed in the first step and soak them in water at a ratio of 1:10 for 30 minutes. Third, bring the raw material mixture soaking solution obtained in the second step to a boil over high heat, then simmer over low heat for 30 minutes, repeating the simmering process several times. The fourth step is to combine the decoctions from several decoctions and concentrate them under reduced pressure until the amount of raw medicinal material is 1 g / mL, which is used as a daily dose. The resulting decoction is the decoction of this invention.

[0044] Example 2: Clinical evaluation of the traditional Chinese medicine composition of the present invention 1. Clinical study design A randomized, parallel-controlled, prospective clinical observation method was used.

[0045] 1.1 Source of Cases A total of 60 patients were admitted to the endocrinology and obesity clinics and inpatient departments of the Shaanxi Provincial Academy of Traditional Chinese Medicine.

[0046] 2. Diagnostic criteria 2.1 Western Medicine Diagnostic Criteria BMI ≥ 27 kg / m 2 Diagnosed abnormal insulin secretion pattern (AISP): compensatory increase in fasting insulin, absence / delay of early phase insulin secretion, delayed secretion peak, and reduced secretion amplitude in the 30-minute OGTT; may be accompanied by hyperlipidemia, hyperuricemia, and snoring during sleep at night.

[0047] 2.2 Traditional Chinese Medicine Diagnostic Criteria (Phlegm-Heat Stasis Syndrome) Main symptoms: obesity, loud snoring at night, abdominal distension, dry mouth and bitter taste; Secondary symptoms: daytime fatigue, yellow urine, sticky or dry stools; Tongue and pulse: The tongue is dark red with a thick, greasy yellow coating, and the pulse is slippery and rapid.

[0048] Diagnostic rules: In addition to tongue appearance (which is mandatory), a diagnosis can be made if ≥3 main symptoms are met, or 2 main symptoms + 2 secondary symptoms are met.

[0049] Scoring rules: Primary symptoms are scored as follows: 6 points for severe, 4 points for moderate, and 2 points for mild; secondary symptoms are scored as follows: 3 points for severe, 2 points for moderate, and 1 point for mild.

[0050] Inclusion and Exclusion Criteria 3.1 Inclusion Criteria (1) Simultaneously meeting the diagnostic criteria for obesity combined with AISP in Western medicine and phlegm-heat stasis syndrome in traditional Chinese medicine; (2) Age 18 to 65 years old; (3) Blood pressure is stable, with systolic blood pressure <180 mmHg and diastolic blood pressure <100 mmHg; (4) Have not taken any weight-loss drugs, traditional Chinese medicine for regulating metabolism, or GLP-1 preparations in the past month; (5) Voluntary participation, signing of informed consent form, and cooperation with OGTT blood collection, routine biochemical testing, physical examination and syndrome questionnaire completion.

[0051] 3.2 Exclusion Criteria (1) Women with secondary obesity such as type I diabetes, Cushing's syndrome, pregnancy, and lactation; (2) Comorbid severe heart, liver, and kidney failure, and severe hematopoietic system diseases; (3) Allergy to any of the ingredients in this compound formula; (4) Severe mental illness or cognitive impairment, unable to cooperate with complete follow-up and OGTT blood test.

[0052] 3.3 Criteria for shedding and rejection (1) Those who do not meet the inclusion criteria after enrollment will be excluded; (2) Discontinuation of medication on one's own, loss of contact during follow-up, or occurrence of severe adverse events are considered dropouts; (3) All cases that have fallen off have completed the final full set of indicator tests and the reasons for falling off have been fully recorded and archived.

[0053] 4. Grouping Initially, 60 cases were included, 3 cases dropped out, and finally 57 cases completed the full OGTT and all tests, including 29 cases in the experimental group and 28 cases in the control group.

[0054] 5. Drug intervention Experimental group: Basic lifestyle intervention (standardized diet control + regular exercise) + the herbal composition of this invention, one dose per day, decocted in water and taken warm twice a day, morning and evening, for 8 consecutive weeks.

[0055] Control group: Received only the same standard of basic lifestyle intervention, without taking the experimental Chinese medicine, for 8 consecutive weeks.

[0056] The two basic intervention programs were completely identical, with only the single variable of whether or not traditional Chinese medicine was taken.

[0057] 6. Observation Indicators 6.1 Core Evaluation of Pancreatic β-cell Secretory Function (a) Oral glucose tolerance test (OGTT), with simultaneous detection of insulin and C-peptide at various time points. Subjects fasted for 8 hours before the intervention and were given fasting venous blood samples in the morning (0 min). They then took 300 mL of 20% anhydrous glucose warm water orally within 5 min. Peripheral venous blood samples were collected at 30 min, 60 min, 120 min and 180 min after glucose administration. All blood samples were centrifuged to separate serum and the tests were completed on the same day.

[0058] A fully automated chemiluminescence immunoassay analyzer, equipped with original manufacturer insulin and C-peptide quantitative detection kits, was used to determine serum insulin and C-peptide concentrations at various time points using chemiluminescence immunoassay (CLIA). Standards and quality control samples were tested simultaneously in strict accordance with the kit instructions, and the internal quality control CV value was <5% to ensure repeatability of the test.

[0059] (ii) Area under the secretion curve (AUC) The area under the curve (AUC) of early-phase insulin (0–30 min) and the area under the curve (AUC) of total insulin secretion (0–180 min) were calculated based on insulin values ​​at each time point.

[0060] (III) Correcting the liver insulin extraction rate by combining C-peptide values By simultaneously detecting C-peptide to correct the first-pass extraction rate of hepatic insulin, the corrected insulin secretion volume truly reflects the native secretory capacity of pancreatic β cells; the time of insulin peak occurrence and peak concentration are recorded to determine whether early phase secretion is missing or delayed.

[0061] (iv) Systematic assessment of β-cell rhythmic secretion characteristics Secretion phase (whether the peak time has shifted earlier), secretion amplitude (whether the peak concentration has recovered), and secretion morphology (whether the early phase secretion deficiency has improved).

[0062] (V) Supporting Basic Indicators Serum glucose was measured using the hexokinase method, with fasting blood glucose and 2-hour postprandial blood glucose being measured simultaneously using a fully automated biochemical analyzer.

[0063] 6.2 Lipid metabolism and accompanying metabolic indicators Fasting venous serum was collected and measured using a fully automated biochemical analyzer employing a direct detection method. Total cholesterol (TC): CHOD-PAP enzymatic method; Triglycerides (TG): GPO-PAP enzymatic method; Low-density lipoprotein cholesterol (LDL-C): Direct modification of enzymes for clearance; High-density lipoprotein cholesterol (HDL-C): Direct immunosuppression method; Fasting serum uric acid: The uricase-peroxidase coupling method was used, and the fully automated biochemical analyzer was used for simultaneous detection. Three days prior to the test, a standardized low-purine diet was followed to exclude interference from high-purine diets and diuretics.

[0064] High and low value quality control sera are set up simultaneously for each batch of samples, and the biochemical detection system calibrators are calibrated regularly to ensure that the result error meets the clinical testing standards.

[0065] 6.3 Body Composition Anthropometrics All measurements were performed by the same trained nurse using the same tools and following standardized procedures. Before the measurement, the subjects removed their heavy coats, shoes, and hats. Weight: Electronic scale, accurate to 0.1 kg; Waist circumference: Wrap a soft measuring tape around the abdomen at the level of the navel, and take the reading at the end of a calm exhalation, accurate to 0.1 cm; Hip circumference: Use a soft measuring tape to horizontally encircle the hips at their widest point, accurate to 0.1 cm.

[0066] Simultaneously calculate waist-to-hip ratio (waist circumference ÷ hip circumference) and BMI = weight (kg) / height (m). 2 .

[0067] 6.4 Quantitative Scoring of Traditional Chinese Medicine Syndromes Referring to the grading and quantification standards for phlegm-heat-blood stasis syndrome in the "Guidelines for the Diagnosis and Treatment of Obesity in Traditional Chinese Medicine", a standardized scale was printed and assessed once before the intervention and once after the 8-week intervention. The assessment was conducted independently by two attending TCM physicians, and the average score was taken as the final score. Main symptoms (obesity, loud snoring at night, abdominal distension, dry mouth and bitter taste): severe 6 points, moderate 4 points, mild 2 points, none 0 points; Secondary symptoms (daytime fatigue, yellow urine, sticky or dry stools): severe 3 points, moderate 2 points, mild 1 point, none 0 points.

[0068] Tongue and pulse are essential criteria for diagnosis, but they are not included in the score; they are only used for syndrome differentiation. The total score is the sum of the scores for all primary and secondary symptoms.

[0069] 6.5 Safety Indicators Complete blood count: EDTA anticoagulated venous blood, fully automated blood cell analyzer to detect a complete set of blood counts including white blood cells, red blood cells, platelets, and hemoglobin; Liver and kidney function: Fasting serum biochemical tests, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, and blood urea nitrogen were detected by rate method. Adverse reaction record: A standardized adverse reaction record form was used. Subjects recorded all abnormal sensations such as gastrointestinal discomfort, dizziness, and rash every day. The physician checked the record during outpatient follow-up and recorded the time of occurrence, duration, severity, whether it was relieved on its own, and whether the medication was discontinued.

[0070] 7. Criteria for Evaluating Therapeutic Effect Significant effect: Fasting insulin decreased significantly; OGTT early phase insulin AUC increased by ≥70%, secretion peak shifted significantly forward, peak concentration recovered, and early phase deficiency was completely improved; fasting and 2-hour postprandial blood glucose returned to normal; all blood lipid indicators returned to normal; weight decreased by ≥4kg; TCM syndrome score of phlegm-heat stagnation decreased by ≥70%, and blood uric acid improved by ≥30%.

[0071] Effective: Fasting insulin levels decreased; early-phase insulin AUC in OGTT increased by 30%–69%, peak secretion shifted earlier, and early-phase secretion deficit was improved; blood glucose and blood lipids improved significantly compared to before intervention; weight decreased by 1.5–3.9 kg; TCM syndrome score for phlegm-heat stagnation decreased by 30%–69%, and blood uric acid improved by 10%–29%.

[0072] Invalid: The above-mentioned valid criteria were not met.

[0073] Overall effectiveness rate = (Number of cases with significant effects + Number of cases with effective results) / Total number of cases in this group × 100% 8. Statistical Analysis and Content Data in this study were analyzed using SPSS 26.0 statistical software. Quantitative data were expressed as mean ± standard deviation (x̄ ± s). Paired t-tests were used for comparisons within groups before and after intervention, and independent samples t-tests were used for comparisons between groups. Count data were expressed as percentages (%) and analyzed using the chi-square test (χ²). 2 Test: P < 0.05 indicates a statistically significant difference, and P < 0.001 indicates a highly significant difference.

[0074] 9. Results The core baseline was evaluated using age, BMI, fasting insulin, early phase insulin AUC, total cholesterol (TC), triglycerides (TG), serum uric acid, and total score of TCM syndrome.

[0075] Table 1. Comparison of baseline data between the two groups of subjects (x̄ ± s)

[0076] As shown in Table 1, there were no statistically significant differences among the groups in all core indicators before the intervention (P > 0.05), indicating that the baselines were balanced and comparable.

[0077] 9.1 Core Evaluation of Pancreatic β-cell Secretory Function The traditional Chinese medicine composition of the present invention was evaluated by assessing the secretory function of pancreatic β cells.

[0078] Table 2 Comparison of quantitative indicators of insulin secretion between the two groups after intervention (x̄±s)

[0079] As shown in Table 2, after 8 weeks of intervention, the experimental group showed significantly better results than the control group in terms of fasting insulin, early-phase insulin AUC, total insulin AUC, and C-peptide-corrected liver insulin extraction rate. The differences between the groups were statistically significant (P < 0.001), indicating that the herbal composition of the present invention can effectively improve the early-phase insulin, total insulin, and C-peptide-corrected liver insulin extraction rate, and significantly reduce fasting insulin.

[0080] Table 3. Comparison of the improvement in insulin secretion phase morphology between the two groups (cases)

[0081] As shown in Table 3, before intervention, all 29 cases in the experimental group exhibited a delayed peak secretion to 120 min and absence of early-phase secretion; after intervention, the peak secretion in 26 cases shifted earlier to 60 min, and early-phase secretion recovered, with only 3 cases showing mild delay. In the control group, the peak secretion was concentrated at 120 min before and after intervention, and 26 cases still showed significant absence of early-phase secretion. The difference in the proportion of improved secretion morphology between the two groups was statistically significant (χ²). 2 =22.361, P<0.001), indicating that taking the traditional Chinese medicine composition of the present invention can effectively restore the earlier phase of insulin secretion peak.

[0082] 9.2 Detection of glucose metabolism, lipid metabolism and accompanying metabolic indicators The traditional Chinese medicine composition of this invention was evaluated by measuring glucose metabolism, lipid metabolism, and accompanying metabolic indicators.

[0083] Table 4 Comparison of glucose, lipid, and uric acid metabolism indicators between the two groups after intervention (xˉ±s, mmol / L)

[0084] As shown in Table 4, after 8 weeks of intervention, the experimental group showed significantly better results than the control group in terms of fasting blood glucose, 2-hour postprandial blood glucose, TC, TG, LDL-C, HDL-C, and serum uric acid. The differences between the groups were statistically significant (P < 0.001), indicating that the herbal composition of the present invention can effectively improve the metabolic indicators of glucose, lipids and serum uric acid.

[0085] 9.3 Body composition measurement The traditional Chinese medicine composition of the present invention was evaluated by changes in body weight, waist circumference, and waist-to-hip ratio.

[0086] Table 5 Comparison of changes in body composition indicators after intervention in the two groups (x̄ ± s)

[0087] As shown in Table 5, paired t-tests before and after intervention in the experimental group revealed highly significant differences in weight, waist circumference, and waist-to-hip ratio (P < 0.001); while in the control group, there were no statistically significant differences in any body composition indicators before and after intervention (P > 0.05). Comparison between groups after intervention showed that the experimental group exhibited significantly greater reductions in weight, waist circumference, and waist-to-hip ratio than the control group (P < 0.001), indicating that the herbal composition of this invention can effectively improve obesity.

[0088] 9.4 Quantitative Scoring of Traditional Chinese Medicine Syndromes (I) Changes in the total score of syndrome The traditional Chinese medicine composition of this invention was evaluated by the total score of TCM syndromes before and after intervention.

[0089] Table 6. Comparison of total TCM syndrome scores before and after intervention in the two groups (x̄ ± s, points)

[0090] Note: The total scores of the two groups after intervention were compared between the two groups. t=13.729, P<0.001.

[0091] As shown in Table 6, the total TCM syndrome scores of both groups decreased after the intervention compared with those before the intervention. The decrease in scores in the experimental group was 73.00%, while that in the control group was 18.00%. The improvement in syndrome scores in the experimental group was significantly better than that in the control group, and the difference was statistically significant (P < 0.001). This indicates that the intervention of the TCM composition of the present invention can significantly improve the total TCM syndrome scores.

[0092] Changes in individual main symptom scores The traditional Chinese medicine composition of this invention was evaluated based on four main symptoms: obesity, loud snoring at night, abdominal distension, and dry and bitter mouth.

[0093] Table 7 Comparison of individual scores for main symptoms before and after intervention in the two groups (x̄ ± s, scores)

[0094] As shown in Table 7, before the intervention, there was no statistically significant difference in the scores of the four main symptoms—obesity, loud snoring at night, abdominal distension, and dry mouth and bitter taste—between the two groups (P > 0.05). After the intervention, the scores of all main symptoms in the experimental group decreased significantly more than those in the control group, and the difference between the groups was statistically significant (P < 0.01). This indicates that after taking the herbal composition of this invention, the scores of the four main symptoms—obesity, loud snoring at night, abdominal distension, and dry mouth and bitter taste—were significantly improved.

[0095] Changes in individual symptom scores The traditional Chinese medicine composition of this invention was evaluated by scoring three sub-symptoms: daytime fatigue, yellow urine, and sticky / dry stools.

[0096] Table 8 Comparison of secondary symptom scores before and after intervention in the two groups (x̄ ± s, scores)

[0097] As shown in Table 8, before the intervention, there was no statistically significant difference in the scores of the three sub-symptoms of daytime fatigue, yellow urine, and sticky / dry stools between the two groups (P > 0.05). After the intervention, the scores of each sub-symptom in the experimental group decreased significantly more than those in the control group, and the difference between the groups was statistically significant (P < 0.05). This indicates that the traditional Chinese medicine composition of the present invention can significantly improve the three sub-symptoms of daytime fatigue, yellow urine, and sticky / dry stools.

[0098] 9.5 Safety Indicators (a) Occurrence of adverse reactions In the experimental group of 29 patients, only 1 patient experienced mild abdominal distension and loose stools on the second day of medication, without nausea, vomiting, rash, dizziness, or other discomfort. The patient did not discontinue medication, and the symptoms resolved spontaneously after 3 days. The incidence of adverse reactions was 3.45% (1 / 29). In the control group, there were no gastrointestinal or systemic adverse reactions throughout the entire course of medication, with an incidence of 0%. The Fisher's exact test was used to compare the incidence of adverse events between the two groups, and the difference was not statistically significant (P=0.483). This indicates that the mild abdominal distension and loose stools that occurred with the herbal composition of this invention do not require symptomatic treatment and resolve spontaneously within 3 days.

[0099] (II) Laboratory Safety Indicators Before and 8 weeks after the intervention, the levels of ALT, AST, creatinine, blood urea nitrogen, white blood cells, and platelets in both groups were within the normal reference range. There were no statistically significant differences within or between the groups before and after the intervention (P>0.05). There were no abnormal indicators related to liver and kidney function or hematopoietic system damage, indicating that taking the traditional Chinese medicine composition of this invention will not produce severe or serious adverse reactions.

[0100] 9.6 Criteria for Evaluating Therapeutic Effect Table 9 Comparison of overall effective rates between the two groups

[0101] As shown in Table 9, the total effective rate in the experimental group was 90.00%, while that in the control group was 53.57%. (χ²) 2 The test results showed that the clinical efficacy of the experimental group was significantly better than that of the control group, and the difference was statistically significant (P=0.006), indicating that the traditional Chinese medicine composition of the present invention can effectively improve the disordered insulin secretion pattern in obese patients.

[0102] 10. Conclusion This invention's herbal composition closely addresses the core pathogenesis of phlegm-heat stagnation and blood stasis. It is not limited to single-point insulin levels but effectively reduces fasting compensatory hyperinsulinemia, shortens peak insulin time, restores peak insulin secretion amplitude, improves early-phase secretion deficiency, and comprehensively repairs pancreatic β-cell secretory function, fundamentally correcting abnormal insulin secretion patterns. It can simultaneously improve total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol, correcting obesity-related dyslipidemia, blocking lipotoxic damage to the pancreas, without requiring the combined use of multiple Chinese and Western medicines. It comprehensively improves systemic metabolic disorders caused by phlegm-heat stagnation and blood stasis; clinical trials showed a low incidence of adverse reactions, making it suitable for long-term intervention.

[0103] Example 3: Typical Clinical Cases The patient is a 46-year-old male who has been obese for 9 years, with a BMI of 31.8. He snores heavily at night and experiences extreme fatigue after meals.

[0104] A complete oral glucose tolerance test (OGTT) revealed a fasting insulin level of 30.2 mU / L and a lack of insulin secretion in the early phase at 30 min. Peak secretion was delayed to 120 min, and the early-phase AUC of insulin was significantly reduced; Blood lipids: triglycerides 3.1 mmol / L, total cholesterol 6.3 mmol / L, low-density lipoprotein 4.2 mmol / L, high-density lipoprotein 0.8 mmol / L; Serum uric acid 498 μmol / L.

[0105] The tongue is dark red with a thick, greasy yellow coating, and the pulse is slippery and rapid, indicating a syndrome of phlegm-heat stagnation and blood stasis.

[0106] Intervention plan: Standardized diet and exercise intervention + the Chinese medicine of this invention, one dose per day, taken in the morning and evening, for 8 consecutive weeks.

[0107] 4-week follow-up: Daytime sleepiness, nighttime snoring, and postprandial fatigue were significantly reduced; 8-week follow-up: According to the OGTT combined with C-peptide correction assessment, the early phase AUC of insulin was significantly improved, the secretion peak was shifted to 60 minutes earlier, and the early phase secretion deficiency was restored; fasting and postprandial blood glucose returned to normal; all blood lipid indicators were up to standard, and blood uric acid returned to normal; weight decreased by 5.3 kg, and symptoms related to phlegm-heat stagnation such as abdominal distension and dry mouth basically disappeared; long-term follow-up showed stable metabolic indicators without rebound.

Claims

1. A traditional Chinese medicine composition for improving the disorder of insulin secretion pattern in obese patients, characterized in that, The traditional Chinese medicine composition consists of the following traditional Chinese medicines in parts by weight: 20-50 parts of mulberry bark, 10-25 parts of platycodon root, 5-20 parts of pinellia tuber, 5-20 parts of trichosanthes fruit, 20-50 parts of acorus tatarinowii rhizome, 5-20 parts of magnolia bark, 5-20 parts of immature bitter orange, 1-5 parts of coptis root, 20-50 parts of salvia miltiorrhiza root, 5-20 parts of euonymus alatus root, 5-20 parts of clematis root, and 10-25 parts of smilax glabra rhizome.

2. The traditional Chinese medicine composition for improving insulin secretion pattern disorder in obese patients as described in claim 1, characterized in that, The traditional Chinese medicine composition consists of the following traditional Chinese medicines in parts by weight: 25-40 parts of mulberry bark, 15-20 parts of platycodon root, 10-15 parts of pinellia tuber, 10-15 parts of trichosanthes fruit, 25-40 parts of acorus tatarinowii rhizome, 10-15 parts of magnolia bark, 10-15 parts of immature bitter orange, 2-4 parts of coptis root, 25-40 parts of salvia root, 10-15 parts of euonymus alatus root, 10-15 parts of clematis root, and 15-20 parts of smilax glabra rhizome.

3. The traditional Chinese medicine composition for improving insulin secretion pattern disorders in obese patients as described in claim 1, characterized in that, The traditional Chinese medicine composition consists of the following traditional Chinese medicines in parts by weight: 30 parts of mulberry bark, 18 parts of platycodon root, 12 parts of pinellia tuber, 12 parts of trichosanthes fruit, 30 parts of acorus tatarinowii rhizome, 12 parts of magnolia bark, 12 parts of immature bitter orange, 3 parts of coptis root, 30 parts of salvia root, 12 parts of euonymus alatus root, 12 parts of clematis root, and 18 parts of smilax glabra rhizome.

4. The traditional Chinese medicine composition for improving insulin secretion pattern disorders in obese patients as described in claim 1, characterized in that, The aforementioned insulin secretion pattern disorder is characterized by the pancreas's inability to precisely match changes in blood glucose levels, leading to decreased cellular sensitivity to insulin and excessive pancreatic insulin secretion. In the long term, this may result in pancreatic dysfunction. The main clinical manifestations include fluctuations in blood glucose, weight changes, fatigue, and increased hunger. In traditional Chinese medicine, the insulin secretion pattern disorder in obese patients is diagnosed as phlegm-heat stagnation syndrome.

5. A traditional Chinese medicine preparation made from the traditional Chinese medicine composition as described in claim 1 for improving insulin secretion pattern disorders in obese patients, characterized in that, The traditional Chinese medicine composition is made from the following traditional Chinese medicines in parts by weight: 20-50 parts of mulberry bark, 10-25 parts of platycodon root, 5-20 parts of pinellia tuber, 5-20 parts of trichosanthes fruit, 20-50 parts of acorus tatarinowii rhizome, 5-20 parts of magnolia bark, 5-20 parts of immature bitter orange, 1-5 parts of coptis root, 20-50 parts of salvia miltiorrhiza root, 5-20 parts of euonymus alatus root, 5-20 parts of clematis root, and 10-25 parts of smilax glabra rhizome.

6. A traditional Chinese medicine preparation made from the traditional Chinese medicine composition for improving insulin secretion pattern disorders in obese patients as described in claim 5, characterized in that, The traditional Chinese medicine preparation is selected from one of the following: ointment, oral liquid, decoction, granule, capsule or tablet.

7. A traditional Chinese medicine preparation made from the traditional Chinese medicine composition for improving insulin secretion pattern disorders in obese patients as described in claim 5, characterized in that, The traditional Chinese medicine preparation contains pharmaceutically acceptable excipients; the pharmaceutically acceptable excipients are pharmaceutical excipients that enhance the efficacy, reduce toxicity, and / or alleviate the side effects of the main drug.

8. A traditional Chinese medicine preparation made from the traditional Chinese medicine composition for improving insulin secretion pattern disorders in obese patients as described in claim 5, characterized in that, The aforementioned insulin secretion pattern disorder is characterized by the pancreas's inability to precisely match changes in blood glucose levels, leading to decreased cellular sensitivity to insulin and excessive pancreatic insulin secretion. In the long term, this may result in pancreatic dysfunction. The main clinical manifestations include fluctuations in blood glucose, weight changes, fatigue, and increased hunger. In traditional Chinese medicine, the insulin secretion pattern disorder in obese patients is diagnosed as phlegm-heat stagnation syndrome.

9. The use of the traditional Chinese medicine composition as described in claim 1 in the preparation of a medicament for improving insulin secretion pattern disorders in obese patients, characterized in that, The traditional Chinese medicine composition is made from the following traditional Chinese medicines in parts by weight: 20-50 parts of mulberry bark, 10-25 parts of platycodon root, 5-20 parts of pinellia tuber, 5-20 parts of trichosanthes fruit, 20-50 parts of acorus tatarinowii rhizome, 5-20 parts of magnolia bark, 5-20 parts of immature bitter orange, 1-5 parts of coptis root, 20-50 parts of salvia miltiorrhiza root, 5-20 parts of euonymus alatus root, 5-20 parts of clematis root, and 10-25 parts of smilax glabra rhizome.

10. The use of the traditional Chinese medicine composition as described in claim 9 in the preparation of a medicament for improving insulin secretion pattern disorders in obese patients, characterized in that, The aforementioned insulin secretion pattern disorder is characterized by the pancreas's inability to precisely match changes in blood glucose levels, leading to decreased cellular sensitivity to insulin and excessive pancreatic insulin secretion. In the long term, this may result in pancreatic dysfunction. The main clinical manifestations include fluctuations in blood glucose, weight changes, fatigue, and increased hunger. In traditional Chinese medicine, the insulin secretion pattern disorder in obese patients is diagnosed as phlegm-heat stagnation syndrome.

Images