Pharmaceutical composition for preventing and / or treating endotoxin-related diseases as well as preparation method and application thereof

Abstract

The invention discloses a pharmaceutical composition for preventing and / or treating endotoxin-related diseases as well as a preparation method and application thereof. The invention finds that the serum endotoxin level rise is one of the fundamental causes or causes of many diseases or symptoms with unknown causes or clear causes, and all people with the serum endotoxin level rise can be treated by using the traditional Chinese medicine composition or the traditional Chinese medicine preparation provided by the invention. The pharmaceutical composition provided by the invention can obviously reduce the level of serum endotoxin and the like, and has a good curative effect of preventing and / or treating endotoxin rise related diseases or symptoms. The traditional Chinese medicine composition or the traditional Chinese medicine preparation provided by the invention can be used for effectively treating unknown etiology or part of diseases or symptoms with clear etiology and increased serum endotoxin, so that the physical and psychological health and the life quality of patients are improved, and the medical expenses and the health care expenses are greatly reduced.

Description

Technical Field

[0001] The present invention belongs to the field of medicine, and particularly relates to a pharmaceutical composition for preventing and / or treating endotoxin-related diseases, and a preparation method and application thereof. Background Art

[0002] The causes and pathogenesis of many diseases or symptoms are unknown, including sub-health conditions, circulatory disorders, allergic / autoimmune diseases, ischemic conditions, hemorrhagic conditions, neurodegenerative diseases, cystic diseases or symptoms, neoplastic diseases such as colorectal adenomas and pituitary tumors, and various syndromes. These patients spend a great deal of time and energy seeking medical treatment, but due to the unknown cause, they cannot receive effective targeted treatment, which consumes a large amount of medical resources.

[0003] Currently, in clinical diagnosis and treatment, serum endotoxin levels are not an indicator that receives much attention. Endotoxin (ET) is a cell wall lipopolysaccharide (LPS) component of Gram-negative bacteria (GNB) that is released during autolysis, growth and reproduction, or lysed during death. Its active center, lipid A (lipid A), is toxic. The inventors of the present invention have found that among people whose serum endotoxins have been tested, almost everyone has endotoxins in their bodies. Not only in disease states, but also in most patients in prodromal states and some patients with fluctuating health states, serum endotoxin levels are elevated to varying degrees. After detoxification treatment, the disease or symptoms are cured or significantly alleviated. Therefore, the inventors believe that elevated serum endotoxin levels are the root cause or one of the causes of many diseases or symptoms of unknown etiology, and are also one of the causes of many "clear-cause" diseases. Summary of the Invention

[0004] The primary object of the present invention is to provide a pharmaceutical composition for preventing and / or treating endotoxin-related diseases.

[0005] Another object of the present invention is to provide a method for preparing the above-mentioned pharmaceutical composition for preventing and / or treating endotoxin-related diseases.

[0006] Another object of the present invention is to provide the use of the above-mentioned Chinese medicine composition or Chinese medicine preparation in the preparation of drugs for preventing and / or treating diseases or symptoms related to elevated serum endotoxin.

[0007] The object of the present invention is achieved by the following technical scheme: a pharmaceutical composition for preventing and / or treating endotoxin-related diseases, which is a traditional Chinese medicine composition capable of reducing serum endotoxin levels, also known as a detoxification prescription; the composition comprises the following ingredients in parts by mass: 70-120 parts of mung beans, 10-30 parts of raw licorice, 10-30 parts of red peony root, 10-20 parts of cooked rhubarb, 10-20 parts of coptis root, 10-20 parts of perilla leaves, 20-40 parts of imperata root, 10-30 parts of umbellate polypore, 10 parts of ginger, 10 parts of celery root ... and 10 parts of celery root. -20 parts; preferably composed of the following ingredients in parts by mass: 85-95 parts of mung beans, 19-21 parts of raw licorice, 19-21 parts of red peony root, 15 parts of cooked rhubarb, 15 parts of coptis chinensis, 15 parts of perilla leaves, 28-32 parts of white imperata roots, 19-21 parts of polyporus, and 15 parts of ginger; preferably, 90 parts of mung beans (packed separately), 20 parts of raw licorice, 20 parts of red peony root, 15 parts of cooked rhubarb, 15 parts of coptis chinensis, 15 parts of perilla leaves, 30 parts of white imperata roots, 20 parts of polyporus, and 15 parts of ginger.

[0008] Each component of the above-mentioned pharmaceutical composition for preventing and / or treating endotoxin-related diseases is prepared according to conventional methods in the art, or can be directly purchased commercially.

[0009] The endotoxin-related disorders refer to endotoxin-related diseases or symptoms.

[0010] A Chinese medicine preparation is prepared from the above-mentioned pharmaceutical composition for preventing and / or treating endotoxin-related diseases, and the preparation method is any of the following methods:

[0011] I. mixing the above-mentioned pharmaceutical composition for preventing and / or treating endotoxin-related diseases and then grinding it to obtain a granular powder;

[0012] II. Packing the mung beans in the pharmaceutical composition for preventing and / or treating endotoxin-related diseases, mixing the other ingredients and then grinding them to obtain granular powder;

[0013] III. extracting the pharmaceutical composition for preventing and / or treating endotoxin-related diseases to obtain an extract;

[0014] IV. Prepare the extract obtained in method III into the desired dosage form.

[0015] The degree of pulverization in Method I and Method II is to pulverize to a particle size of 60-100 mesh, preferably 65-80 mesh.

[0016] The extraction methods described in Mode III include decoction, maceration, percolation, reflux extraction, steam distillation, etc.; decoction is preferred.

[0017] The specific steps of the decoction method are preferably as follows:

[0018] (1) Boil mung beans with water to obtain mung bean water;

[0019] (2) soaking the ingredients of the pharmaceutical composition except mung beans in the mung bean water obtained in step (1); then decocting to obtain an extract.

[0020] The decocting time in step (1) is preferably 25-40 minutes.

[0021] The soaking time in step (2) is preferably more than 10 minutes; more preferably 20-60 minutes; further preferably 20-30 minutes.

[0022] The amount of mung bean water in step (2) is calculated based on 2-10 times the amount of the ingredients in the pharmaceutical composition other than mung beans; preferably 9-10 times; more preferably 10 times.

[0023] The degree of decoction in step (2) is preferably calculated based on 150-300 ml of extract per 160-330 g of the pharmaceutical composition; more preferably, 200 ml of extract per 160-330 g of the pharmaceutical composition.

[0024] The specific steps of decocting in step (2) are preferably as follows: heating to boiling and then continuing heating for more than 10 minutes, preferably 20 minutes to 1 hour, and more preferably 20-30 minutes.

[0025] Preferably, steps (1) and (2) are repeated to more fully extract the pharmaceutical composition; and the pharmaceutical solution obtained the second time is combined with the pharmaceutical solution obtained the first time.

[0026] The dosage forms described in mode IV include granules, tablets, capsules, pills, granules, powders, oral liquid preparations, etc.

[0027] The tablets include dispersible tablets and orally disintegrating tablets.

[0028] The capsules include soft capsules and hard capsules.

[0029] The pills are preferably drop pills.

[0030] The oral liquid preparations include oral liquids, syrups and suspensions.

[0031] The dosage form is prepared according to conventional means in the art; for example, pharmaceutically acceptable excipients may be added as needed to prepare the corresponding dosage form.

[0032] The pharmaceutically acceptable excipients include, but are not limited to, diluents, disintegrants, lubricants, binders, colorants, flavorings, wetting agents, etc.; specific substances include, but are not limited to, lactose, mannose, starch, polyvinyl pyrrolidone, magnesium stearate, sodium lauryl sulfate, sorbitol, methyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, lecithin, gelatin, p-hydroxybenzoate, Tween 80, polyethylene glycol, cyclodextrin, etc.

[0033] The granules are preferably prepared by the following steps: concentrating the extract and drying to obtain granules; or concentrating the extract, adding pharmaceutically acceptable excipients, and drying to obtain granules.

[0034] The tablets may be optionally coated.

[0035] The use of the above-mentioned Chinese medicine composition or Chinese medicine preparation in the preparation of drugs for preventing and / or treating diseases or symptoms related to elevated serum endotoxin.

[0036] The content of serum endotoxin in normal human serum varies according to different test reagents and methods; the present invention uses endotoxin Limulus amebocyte endotoxin quantitative test-chemiluminescence method, and the normal value in the kit manual is ≤5pg / ml.

[0037] The diseases related to elevated serum endotoxin levels are diseases or symptoms caused by elevated endotoxin levels, often without fever; preferably, the diseases are diagnosed as having an unknown cause or a "clear cause" and elevated endotoxin levels.

[0038] The cause of disease mentioned in the "clear cause of disease" does not include serum endotoxin.

[0039] The diseases or symptoms associated with elevated serum endotoxins include but are not limited to: (1) diseases or symptoms of unknown etiology: fatigue syndrome or weakness or even paralysis of unknown etiology that can be restored to normal after detoxification treatment, insomnia, drowsiness, snoring during sleep, dizziness, tinnitus, deafness, slowed or dulled reactions, premature aging, disorientation, mouth ulcers, partial hypotension, primary hypertension, recurrent palpitations with normal electrocardiogram, loss of appetite and nausea with / without vomiting when gastroscopy is basically normal, sticky and unformed stools, constipation, non-infectious loose stools, joint pain and migratory pain that are not responsive to anti-inflammatory drugs, glucosamine or sodium hyaluronate injections, etc. (2) Circulatory disorders: migraine, glaucoma, optic vein occlusion syndrome and partial retinal detachment, hemorrhoids, swelling of the lower limbs or even the whole body, varicose veins with or without thrombosis and organization, enlargement of the lower limbs, idiopathic pulmonary hypertension, cyanosis of the lips with normal platelet count and purpura or ecchymosis on the skin, etc.; pleural effusion or ascites of unknown etiology, etc. (3) Allergic diseases: allergic rhinitis, asthma, allergic dermatitis and allergic conjunctivitis, etc. (4) Skin diseases: acne, eczema, atopic dermatitis, skin ulcers, vitiligo, chloasma, carbuncle, furuncle and skin calcification, etc. (5) Ischemic diseases: cerebral ischemia and infarction, atrial fibrillation, myocardial ischemia and infarction, renal infarction, splenic infarction and pancreatic necrosis, etc. (6) Hemorrhagic diseases: gingival bleeding, epistaxis, fundus hemorrhage, cerebral hemorrhage and abdominal hematoma, etc. (7) Autoimmune diseases: Sjögren's syndrome, rheumatoid arthritis, autoimmune hepatitis, autoimmune thyroiditis, sclerosing cholangitis, IgG4-related diseases, pemphigus and lupus erythematosus, etc. (8) Degenerative diseases: ① Neurodegenerative diseases: memory loss, cognitive impairment and dementia, etc.; ② Lens protein denaturation: cataracts; ③ Macular degeneration and vitreous opacities; ④ Intervertebral disc degeneration; etc. (9) Cystic diseases: liver cysts, kidney cysts, ovarian cysts, polycystic ovary syndrome and sacral cysts, etc. (10) Benign and malignant tumors of epithelial, mesenchymal and neuroendocrine cell origin in various systems and organs: such as ① adenomas and adenocarcinomas of the large and small intestine, adenomas, carcinomas and sarcomas of the stomach, liver, bile duct, gallbladder and pancreas, solid pseudopapillary tumors of the pancreas, lung cancer and sarcoma, etc.; ② squamous intraepithelial neoplasia and squamous cell carcinoma; ③ benign and malignant tumors of skin appendages; ④ soft tissue tumors: hemangioma, angiosarcoma, lipoma, liposarcoma, leiomyoma and leiomyosarcoma, neurothecoma, gastric Intestinal stromal tumors and undifferentiated sarcomas, etc.; ⑤ Benign and malignant urothelial tumors; ⑥ Occurrence / recurrence of central nervous system tumors such as pituitary tumors; ⑦ Lymphoma / leukemia, etc.; ⑧ Endometrial intraepithelial neoplasia, endometrial carcinoma, uterine leiomyoma and leiomyosarcoma, endometrial stromal tumors; ovarian, fallopian tube, cervical, vaginal and vulvar tumors, vulvar leukoplakia, etc.; ⑨ Benign and malignant tumors of the breast, prostate, testicle and epididymis, etc.; ⑩ Adrenal gland, some thyroid and parathyroid gland tumors; Gingival tumor, etc. (11) Inflammatory diseases: vasculitis, myocarditis with fibrosis, pneumonia, various types of hepatitis, liver fibrosis and cirrhosis, liver abscess, cholecystitis and cholangitis, hemorrhagic necrotizing pancreatitis, chronic pancreatitis and fibrosis, ulcerative colitis, glomerulonephritis, glomerular fibrosis and sclerosis, glandular cystitis, ureteritis and stenosis, non-infectious urethritis, non-infectious mastitis, uveitis, thyroiditis, neuritis and aseptic inflammation, etc. (12) Atrophic diseases: gingival atrophy, myocardial fibrosis and atrophy, atrophy of gastrointestinal mucosal glands and smooth muscle, pancreatic atrophy, atrophy of bladder and smooth muscle tissue around the eyeball, atrophy of testicles, seminal vesicles and prostate, atrophy of squamous epithelium, atrophy and reduction of hair follicles, etc. (13) Proliferative diseases: vascular nodular hyperplasia, endometrial hyperplasia, hyperplasia of breast, sweat glands and prostate, adrenal hyperplasia, etc.; myelodysplastic syndrome and lymphoproliferative lesions, etc. (14) Stones: urinary tract stones and gallbladder stones. (15) Benign polyps: fundic gland polyps, gallbladder polyps, and endometrial polyps. (16) Female and male reproductive system diseases: ① Hypogonadism or hypergonadism of unknown etiology; ② Amenorrhea, dysmenorrhea, female infertility, premature birth, miscarriage, intrauterine fetal death, pregnancy-induced hypertension syndrome, and hydatidiform mole; ③ Male infertility. (17) Some fevers or low body temperature. (18) Mental or psychological abnormalities: bad temper, anxiety, depression, and autism. (19) Abnormal laboratory test indicators: occult blood in urine and / or urine protein (+), elevated cholesterol, leukopenia and thrombocytopenia, elevated aspartate aminotransferase (AST), hypothyroidism or hyperthyroidism, etc. (20) Microscopic pathological changes: pulmonary edema, microscopic polyangiitis, protein casts in renal tubules, pink-stained material and red blood cells visible in the glomerular capsule, i.e., dilatation of the renal capsule, microthrombosis such as microthrombosis and thrombus-like material formation in the glomerular capillaries, local necrosis of the glomerulus or cell proliferation and apoptosis in the glomerulus, neutrophil infiltration in the glomerulus, glomerular and tubular atrophy, renal interstitial edema, amyloidosis, fibrosis and calcification, etc. (21) Others: hepatic encephalopathy, hepatorenal syndrome, nephrotic syndrome, uremia, acute lung injury or acute respiratory distress syndrome, metabolic syndrome, menopausal syndrome, Churg-Strauss syndrome and Vogt-Koyanagi-Harada syndrome, etc.

[0040] A method for preventing and / or treating diseases or symptoms associated with elevated serum endotoxins comprises administering a therapeutically effective amount of the above-mentioned pharmaceutical composition or traditional Chinese medicine preparation to an individual in need.

[0041] Those skilled in the art will appreciate that clinicians can determine the dosage of the aforementioned Chinese medicine composition or preparation based on the patient's specific condition and the severity of the disease.

[0042] The above-mentioned pharmaceutical composition has better efficacy when the decoction obtained by the decoction method is allowed to cool at room temperature before taking. It is preferably taken half an hour or more before meals, and those with stomach problems can take it immediately after meals.

[0043] Based on the research content of the present invention, the present invention also proposes the following scheme: the use of drugs that reduce serum endotoxin levels in the preparation of drugs for preventing and / or treating diseases or symptoms of unknown causes or "clear causes" and elevated endotoxin levels.

[0044] The disease of unknown etiology in the present invention refers to a disease or symptom whose cause cannot be determined through routine examinations and existing medical means.

[0045] The Chinese medicine composition provided by the present invention is a non-specific detoxification prescription formed by adding mung bean and licorice soup to the empirical prescription inherited by Professor Jiang Liangduo from his teacher Zhang Xuewen, a master of traditional Chinese medicine, and is used to treat these diseases or symptoms of unknown causes, achieving a high therapeutic effect.

[0046] The Chinese medicine composition provided by the present invention is formulated for the pathological characteristics of poisoning, "internal accumulation of turbid toxins, stagnant blood circulation, and damage to vital energy", and has the effects of detoxification and detoxification. The prescription of the present invention detoxifies and clears away heat and stasis, promotes the flow of qi, and takes into account vital energy, which can make the evil toxins go out; mung beans and raw licorice in the prescription detoxify and clear away heat, mung beans are also diuretic, and licorice is also a tonifying agent; Imperata root cools blood and stops bleeding, clears heat and promotes diuresis; red peony root clears heat and cools blood, detoxifies and removes stasis; Coptis root clears heat and dries dampness, purges fire and detoxifies; cooked rhubarb purges heat, promotes bowel movements and detoxifies, removes stasis and stops bleeding; Polyporus umbellatus promotes diuresis and eliminates dampness, and cooperates with mung beans and Imperata root to conduct heat and toxins out of urine; perilla leaves and ginger both dissipate cold, detoxify fish and shrimp, etc., and promote the flow of qi, which is beneficial Modern medical research believes that the protein, tannin and flavonoids in mung beans can combine with organophosphorus pesticides, mercury, arsenic and lead compounds to form precipitates, reducing or eliminating the toxicity of the latter. Mung beans also have antibacterial and antifungal effects, and antioxidant effects. Coumarin, alkaloids, phytosterols and saponins can enhance the body's immune function and increase the number or function of phagocytes. Glycyrrhizin and ammonium glycyrrhizate have detoxification, liver protection, antibacterial, It has antiviral and anti-allergic effects; Imperata root can relieve glomerular vasospasm, increase renal blood flow and glomerular filtration rate, and produce diuretic effects. The water extract of Imperata root reduces capillary permeability; the active ingredients of Paeonia lactiflora have a high binding effect with LPS and are resistant to various pathogens; Rhubarb affects colonic water absorption by reducing the expression of aquaporin (AQP) 3 and AQP4, increasing intestinal water content, and reducing the expression of vasoactive intestinal peptide, thereby increasing intestinal peristalsis and bowel movements and accelerating endotoxin excretion. Rhein has antibacterial, antiviral and immunomodulatory effects, emodin has an inhibitory effect on various bacteria, and chrysophanol can enhance the liver's detoxification function and promote bile secretion; Coptis chinensis can resist various pathogens and their toxins, and berberine has anti-inflammatory and immune-regulating effects, which can prevent the activation of tumor-related pathways; Poria promotes toxin excretion, and Poria polysaccharides can enhance the body's cellular immune function, reduce plasma cortisol, and restore hyperactive adrenal cortex function to normal.

[0047] The present invention objectively evaluates the efficacy of the pharmaceutical composition of the present invention in preventing and / or treating endotoxin-related diseases or symptoms through clinical observation and comparison of patients' main clinical symptoms, stool characteristics, quality of life, serum endotoxin levels, etc. Clinical trials have shown that the Chinese medicine composition of the present invention has the following effects:

[0048] (1) The Chinese medicine composition or Chinese medicine preparation provided by the present invention can significantly reduce the level of serum endotoxins, etc., and has a good therapeutic effect in preventing and / or treating diseases or symptoms related to increased endotoxins.

[0049] (2) The Chinese medicine composition or Chinese medicine preparation provided by the present invention can effectively treat diseases or symptoms caused by elevated serum endotoxins, thereby improving the patient's physical and mental health and quality of life, and greatly reducing medical expenses and health care costs.

[0050] (3) Based on the present invention, it has been demonstrated that elevated serum endotoxin levels are the root cause or one of the causes of many diseases or symptoms of unknown etiology. Elevated serum endotoxin levels are also found in some conditions with previously known etiologies. Any patient with elevated serum endotoxin levels can be treated with the Chinese medicine composition or preparation provided by the present invention. DETAILED DESCRIPTION

[0051] The present invention will be further described in detail below with reference to examples, but the embodiments of the present invention are not limited thereto.

[0052] Example 1

[0053] Weigh 90g of mung beans (packed separately, first decoct the mung beans for 30 minutes to obtain brown mung bean water); 20g of raw licorice, 20g of red peony root, 15g of cooked rhubarb, 15g of coptis root, 15g of perilla leaf, 30g of imperata rhizome, 20g of polyporus, and 15g of ginger (all purchased from Dongzhimen Hospital of Beijing University of Chinese Medicine or a Chinese medicine store), mix them, add the brown mung bean water to the other drug mixture, soak for 30 minutes, boil over high heat, change to low heat and continue heating for about 20 minutes until the remaining medicinal liquid is about 200ml, repeat the above decoction process, use a total of 3000ml of mung bean water, mix the two obtained medicinal liquids to obtain a Chinese medicine preparation.

[0054] Example 2

[0055] Weigh 90g of mung beans (pack separately, first boil the mung beans for 30 minutes to obtain brown mung bean water); 20g of raw licorice, 20g of red peony root, 15g of cooked rhubarb, 15g of coptis root, 15g of perilla leaf, 30g of Imperata root, 20g of Poria cocos, and 15g of ginger (all purchased from Dongzhimen Hospital of Beijing University of Chinese Medicine or Chinese medicine stores), mix, and grind to a particle size of 65-80 mesh to obtain granules. When taking, brew with brown mung bean water.

[0056] Example 3

[0057] In this embodiment, the definition of insomnia patients with unknown etiology is as follows: patients who cannot sleep at night due to reasons other than physiological reasons, such as drinking a lot of tea, coffee or alcohol during the day, or major changes in life.

[0058] Fourteen patients with unexplained insomnia (7 males and 7 females) aged 72, 68, 67, 22, 73, 42, 38, 69, 57, 33, 66, 39, 59, and 54 years old, respectively. Serum endotoxin levels were 334.9, 53.23, 30.5, 10.5, 72.88, 117.99, 62.3, 31.74, 55.57, 80.6, 58.88, 112.56, 113.03, and 69.29 pg / ml, respectively. They took 13, 5, 2, 7, 16, 24, 7, 5, 8, 14, 14, 7, 3, and 3 detoxification prescriptions, respectively. The dosage is one dose per day, taken once in the morning and evening, generally before meals. For patients with stomach problems, take the prescription immediately after meals. It should be noted here that when patients visit the doctor, the doctor generally prescribes 7 doses of medicine for a course of treatment. Some patients see significant results after taking the medicine and then stop taking it and visit the doctor again, while some patients take all the medicine before visiting the doctor again.

[0059] The serum endotoxin levels of the first 12 patients dropped to normal (5pg / ml), insomnia disappeared, sleep became normal, and insomnia did not recur.

[0060] The first patient stopped taking the detoxification prescription after his insomnia and other symptoms disappeared. However, insomnia recurred and cerebral infarction occurred again 3 months later. After the cerebral infarction recurred after being treated with Western medicine (aspirin, clopidogrel, etc.) and Chinese medicine (without the detoxification prescription, but with Chinese medicine Stroke No. 1 or 2), he took 7 more detoxification prescriptions. Finally, the serum endotoxin level returned to normal, insomnia disappeared, and the patient was discharged from the hospital after his condition improved.

[0061] The last two patients took only three doses of detoxification prescriptions, and their insomnia symptoms were alleviated. However, insomnia reappeared a few days after stopping the medication. This was closely related to the fact that they took too few detoxification prescriptions and failed to reduce the serum endotoxin level to normal before stopping the medication.

[0062] Example 4

[0063] For patients with unexplained fatigue, clinical doctors ruled out anemia, blood and tumor diseases, liver and kidney diseases, etc., and diagnosed them with fatigue of unknown cause or fatigue syndrome.

[0064] There were 3 patients with fatigue of unknown etiology, including 1 male and 2 females, aged 38, 73 and 54 years old, respectively. The serum endotoxin levels were 51.7, 72.88 and 97.1 pg / ml, respectively. After taking 7, 8 and 14 detoxification prescriptions, respectively, the serum endotoxin levels dropped to normal and the fatigue disappeared.

[0065] Example 5

[0066] Patients with unexplained tinnitus are those whose otolaryngology department cannot find the cause and are diagnosed with tinnitus awaiting investigation.

[0067] Two patients with unexplained tinnitus were male, aged 38 and 72 years old respectively. Their serum endotoxin levels were 51.7 and 334.9 pg / ml respectively. After taking 7 and 13 detoxification prescriptions respectively, their serum endotoxin levels dropped to normal (5 pg / ml) and the tinnitus disappeared.

[0068] Example 6

[0069] Two patients, both women, aged 56 and 73, presented with unexplained lower limb swelling (with normal heart, liver, kidney, and thyroid function). The former had a varicose vein in the left lower limb and pitting edema in the anterior tibia. Her serum endotoxin level was 100.06 pg / ml, while the latter had bilateral lower limb swelling and a serum endotoxin level of 72.88 pg / ml. After taking 20 and 8 detoxification prescriptions, respectively, their serum endotoxin levels returned to normal (5 pg / ml), and the lower limb swelling resolved.

[0070] There was a patient with thickening of the right lower limb. The male was 57 years old and had varicose veins in the right lower limb. The circumference of the calf and ankle were 42cm and 24cm respectively, which was thicker than the left lower limb. The circumference of the calf and ankle of the left lower limb were 40cm and 23.5cm respectively. The serum endotoxin level was 108.5pg / ml. After taking 6 doses of detoxification prescriptions, the circumference of the right calf was reduced to 41.5. After taking 9 doses of detoxification prescriptions, the circumference of the right calf was reduced to 41cm. The serum endotoxin level was rechecked and returned to normal (5pg / ml).

[0071] Example 7

[0072] Three patients with migraine of unknown etiology (no obvious abnormalities were found in imaging examinations) were female, aged 56, 59 and 54 years old, with serum endotoxin levels of 58.74, 113.03 and 69.29 pg / ml, respectively. After taking 10, 3 and 3 detoxification prescriptions, respectively, the serum endotoxin level of the first patient dropped to normal (5 pg / ml) and the migraine did not recur. The migraine symptoms of the latter two patients improved.

[0073] Example 8

[0074] Nine patients presented with sticky, unformed stools. Among them, four were males aged 68, 67, 72, and 38 years old, with serum endotoxin levels of 53, 30.5, 334.9, and 62.3 pg / ml, respectively; and five were females aged 42, 69, 57, 59, and 54 years old, with serum endotoxin levels of 117.99, 31.74, 55.57, 113.03, and 69.29 pg / ml, respectively. After taking 13, 2, 16, 5, 7, 5, 8, 3, and 3 detoxification prescriptions, respectively, their serum endotoxin levels all dropped to normal (5 pg / ml), and their stools became formed and returned to normal. The third patient, initially treated with norfloxacin, still presented with sticky, unformed stools. After taking the detoxification prescription, their stools returned to normal. There were two other patients with sticky and unformed stools, one male and one female, aged 63 and 61 respectively. The serum endotoxin levels of both patients were 500pg / ml. After taking two detoxification prescriptions, their stools became formed and no longer sticky.

[0075] Example 9

[0076] Four patients with eye diseases such as branch retinal vein occlusion, dry eyes, glaucoma, and retinal artery insufficiency, all had their serum endotoxin levels reduced to normal, their intraocular pressure decreased, and their symptoms and eye signs such as eye swelling or pain were alleviated. The second patient's right eye vision was significantly restored, as shown in Table 1:

[0077] Table 1

[0078]

[0079]

[0080] Example 10

[0081] There were 4 patients with cerebral infarction, including 1 male and 3 females, aged 72, 54, 70 and 51 years old respectively. The serum endotoxin levels were 334.9, 97.1, 11.2 and 46.44 pg / ml respectively. After taking 13, 14, 4 and 5 detoxification prescriptions respectively, the serum endotoxin levels were reduced to normal and cerebral infarction did not recur.

[0082] Among them, Case 1 was hospitalized for the first cerebral infarction and was discharged after symptoms improved after conventional treatment of Chinese and Western medicine (without detoxification). Ten days after discharge, cerebral infarction occurred again and he was hospitalized for the second time. The hospital continued to treat him according to the treatment plan of the first hospitalization (without detoxification). As a result, the patient suffered a third cerebral infarction during hospitalization. At this time, after testing the serum endotoxin, 7 doses of detoxification prescription were added to the original treatment, and the cerebral infarction stopped; then the prescription was taken until the serum endotoxin level dropped to normal, and there was no further cerebral infarction.

[0083] Case 3 was a patient who had suffered a cerebral infarction and received combined traditional Chinese and Western medicine treatment. However, examination revealed no cerebral artery occlusion and mild stenosis, indicating an unknown etiology. After serum endotoxin testing, the patient took a detoxification prescription until the serum endotoxin level returned to normal. Follow-up has continued for over a year, and the patient has not experienced a recurrence of cerebral infarction.

[0084] Example 11

[0085] A patient suffered from fatigue and lower limb swelling for more than 40 years. In severe cases, the whole body swelled up. Various Western medicine treatments were ineffective. Taking Shenshao Capsules and Xuesetong was effective, but the medication could not be stopped. The symptoms relapsed after stopping the medication. After taking 8 sets of detoxification prescriptions in a row, the symptoms disappeared. One month later, the above symptoms recurred. The serum endotoxin level was significantly increased (72.88pg / ml). After taking 8 sets of detoxification prescriptions in a row, the symptoms disappeared and the serum endotoxin level was normal (5pg / ml). It has been 2 years since then and there has been no recurrence.

[0086] Example 12

[0087] The treatment results of clinical cases with different symptoms are shown in Table 2:

[0088] Table 2

[0089]

[0090] Note: The treatment mentioned here refers to the treatment after taking the detoxification prescription.

[0091] Example 13

[0092] Four patients with sleep snoring (two males, aged 56 and 63 years old, respectively) had serum endotoxin levels of 108.5 and 500 pg / ml, respectively; two females, aged 61 and 53 years old, had serum endotoxin levels of 500 and 17.0 pg / ml, respectively. One patient with light sleepiness (male, 57 years old) had a serum endotoxin level of 17.8 pg / ml. After each of the five patients took one detoxification prescription, four of them stopped snoring, and the light sleeper experienced significantly more restful sleep.

[0093] Drug efficacy evaluation

[0094] The present invention objectively and systematically evaluates the efficacy of the pharmaceutical composition of the present invention on endotoxin-related diseases or symptoms by comparing the main clinical symptoms, stool characteristics, quality of life, and serum endotoxin levels of patients through clinical studies.

[0095] 1. Case Selection

[0096] 1. Diagnostic criteria for endotoxin-related diseases

[0097] One or more of the following criteria: ① Elevated serum endotoxin levels; ② Significant relief or disappearance of symptoms after taking detoxifying drugs or health products such as detoxification prescriptions, and the diagnosis of endotoxin-related diseases.

[0098] The following aspects should be noted when diagnosing endotoxin-related diseases or symptoms:

[0099] (1) Before testing the serum endotoxin level, the patient should not take any drugs or health products with detoxification and / or elimination effects.

[0100] (2) The stool characteristics of endotoxin-related diseases or symptoms have certain characteristics, such as sticky and unformed stools, loose stools, loose or watery stools, and long-term constipation.

[0101] 2. Inclusion criteria

[0102] (1) Meet the diagnostic criteria for endotoxin-related diseases or symptoms;

[0103] (2) Aged between 7 and 95 years, regardless of gender;

[0104] (3) Informed consent: volunteers were required to participate in the study and signed the informed consent form. The informed consent process complied with GCP regulations.

[0105] 3. Exclusion criteria

[0106] (1) Those who have taken drugs or health products with detoxification and / or detoxification effects;

[0107] (2) The person’s health condition is not suitable for blood collection;

[0108] 4. Elimination criteria

[0109] Enrolled cases who meet any of the following criteria should be excluded:

[0110] (1) Misdiagnosis and misadmission;

[0111] (2) Those who have never taken medication;

[0112] (3) Those without any test records;

[0113] (4) The efficacy of the treatment cannot be evaluated due to the use of prohibited drugs.

[0114] 2. Drug Use

[0115] Monitor endotoxin levels while taking the detoxification prescription. For those with endotoxin levels higher than 50pg / ml, the endotoxin level should generally be rechecked after taking 7 doses. If it has not returned to normal, consider taking a few more doses based on the previous reduction in level and then recheck until the endotoxin level returns to the normal range.

[0116] 3. Endotoxin detection method

[0117] Endotoxin quantification test of Limulus amebocyte lysate-chemiluminescence method.

[0118] IV. Precautions

[0119] The serum endotoxin level must be dynamically monitored when taking the pharmaceutical composition of the present invention. Once the serum endotoxin level test result is normal, the pharmaceutical composition of the present invention should be discontinued.

[0120] 5. Experimental Results

[0121] Clinical trials have shown that the medicament prepared using the pharmaceutical composition of the present invention can significantly reduce serum endotoxin levels.

[0122] No obvious abnormalities were found in the blood routine, liver and kidney function and electrocardiogram tests performed during or after treatment.

[0123] Clinical trials have shown that the medicament prepared using the pharmaceutical composition of the present invention can effectively and safely treat endotoxin-related diseases or symptoms, with an efficacy of 100%.

[0124] The above describes the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for preventing and / or treating endotoxin-related diseases, characterized in that The invention is composed of the following ingredients in parts by mass: 70-120 parts of mung beans, 10-30 parts of raw licorice, 10-30 parts of red peony root, 10-20 parts of cooked rhubarb, 10-20 parts of coptis root, 10-20 parts of perilla leaves, 20-40 parts of imperata rhizome, 10-30 parts of polyporus and 10-20 parts of ginger.

2. The pharmaceutical composition for preventing and / or treating endotoxin-related diseases according to claim 1, characterized in that The invention is composed of the following ingredients in parts by mass: 85-95 parts of mung beans, 19-21 parts of raw licorice, 19-21 parts of red peony root, 15 parts of cooked rhubarb, 15 parts of coptis root, 15 parts of perilla leaves, 28-32 parts of imperata rhizome, 19-21 parts of polyporus and 15 parts of ginger.

3. A Chinese medicine preparation, characterized in that: The composition is prepared from the pharmaceutical composition for preventing and / or treating endotoxin-related diseases according to claim 1 or 2.

4. The method for preparing the Chinese medicine preparation according to claim 3, wherein: The preparation method is any of the following:

1. Mixing and grinding the pharmaceutical composition for preventing and / or treating endotoxin-related diseases according to claim 1 or 2 to obtain a granular powder; II. Packing the mung beans in the pharmaceutical composition for preventing and / or treating endotoxin-related diseases according to claim 1 or 2, mixing the other ingredients and then grinding them to obtain granular powder; III. extracting the pharmaceutical composition for preventing and / or treating endotoxin-related diseases according to claim 1 or 2 to obtain an extract; IV. Prepare the extract obtained in method III into the desired dosage form.

5. The method for preparing the Chinese medicine preparation according to claim 4, wherein: The degree of pulverization described in Method I and Method II is to pulverize to a particle size of 60-100 mesh; The extraction methods described in Method III include decoction, maceration, percolation, reflux extraction, and steam distillation; The dosage forms described in mode IV include granules, tablets, capsules, pills, granules, powders, and oral liquid preparations.

6. The method for preparing the Chinese medicine preparation according to claim 5, wherein: The specific steps of the decoction method are as follows: (1) Boil mung beans with water to obtain mung bean water; (2) soaking the ingredients of the pharmaceutical composition except mung beans in the mung bean water obtained in step (1); then decocting to obtain an extract; The dosage form can be prepared by adding pharmaceutically acceptable excipients as needed to obtain the corresponding dosage form.

7. The method for preparing the Chinese medicine preparation according to claim 6, wherein: The decoction time in step (1) is 25-40 minutes; The soaking time in step (2) is more than 10 minutes; The amount of mung bean water in step (2) is calculated based on the amount of the mung bean water being 2-10 times the amount of the ingredients of the pharmaceutical composition according to claim 1 or 2 except for mung beans; The degree of decoction in step (2) is calculated based on 150-300 ml of extract for every 160-330 g of the pharmaceutical composition; The specific steps of decocting in step (2) are as follows: heating to boiling and then continuing to heat for more than 10 minutes; The pharmaceutically acceptable excipients include diluents, disintegrants, lubricants, adhesives, colorants, flavorings, and wetting agents.

8. Use of the Chinese medicine composition according to any one of claims 1 to 2 or the Chinese medicine preparation according to claim 3 in the preparation of a drug for preventing and / or treating diseases or symptoms associated with elevated serum endotoxin.

9. The use according to claim 8, characterized in that: The diseases or symptoms associated with elevated serum endotoxin levels are diseases or symptoms caused by elevated endotoxin levels, which are often not accompanied by fever.

10. The use according to claim 8, characterized in that: The diseases or symptoms associated with elevated serum endotoxins are: (1) diseases or symptoms of unknown etiology: fatigue syndrome or weakness or even paralysis of unknown etiology that can be restored to normal after detoxification treatment, insomnia, drowsiness, snoring during sleep, dizziness, tinnitus, deafness, slowed or dulled reaction, premature aging, disorientation, mouth ulcers, partial hypotension, primary hypertension, recurrent palpitations with normal electrocardiogram, loss of appetite and nausea with / without vomiting with basically normal gastroscopy, sticky and unformed stools, constipation, non-infectious loose stools, joint pain and migratory pain that are not treated with anti-inflammatory drugs, glucosamine or sodium hyaluronate injections; (2) circulatory disorders: migraine, glaucoma, optic vein occlusion syndrome and Partial retinal detachment, hemorrhoids, swelling of the lower limbs or even the whole body, varicose veins with / without thrombosis and organization, thickening of the lower limbs, idiopathic pulmonary hypertension, cyanosis of the lips with normal platelet count and purpura or ecchymosis on the skin; pleural effusion or ascites of unknown etiology; (3) Allergic diseases: allergic rhinitis, asthma, allergic dermatitis and allergic conjunctivitis; (4) Skin diseases: acne, eczema, atopic dermatitis, skin ulcers, vitiligo, chloasma, carbuncle, furuncle and skin calcification; (5) Ischemic diseases: cerebral ischemia and infarction, atrial fibrillation, myocardial ischemia and infarction, renal infarction, splenic infarction and pancreatic necrosis; (6) Hemorrhagic diseases: gingival bleeding, epistaxis, fundus hemorrhage, cerebral hemorrhage and abdominal hematoma; (7) Autoimmune diseases Epidemiological diseases: Sjögren's syndrome, rheumatoid arthritis, autoimmune hepatitis, autoimmune thyroiditis, sclerosing cholangitis, IgG4-related diseases, pemphigus and lupus erythematosus; (8) Degenerative diseases: ① Neurodegenerative diseases: memory loss, cognitive impairment and dementia; ② Lens protein denaturation: cataract; ③ Macular degeneration and vitreous opacity; ④ Intervertebral disc degeneration; (9) Cystic diseases: liver cysts, kidney cysts, ovarian cysts, polycystic ovary syndrome and sacral cysts; (10) Benign and malignant tumors of epithelial, mesenchymal and neuroendocrine cell origin in various systems and organs: ① Adenomas and adenocarcinomas of the large and small intestine, adenomas, carcinomas and sarcomas of the stomach, liver, bile duct, gallbladder and pancreas, solid pseudopapillary tumors of the pancreas, ② Lung cancer and sarcoma occurrence / recurrence; ② Squamous intraepithelial neoplasia and squamous cell carcinoma occurrence / recurrence; ③ Benign and malignant tumors of skin appendages; ④ Soft tissue tumors: hemangioma, angiosarcoma, lipoma, liposarcoma, leiomyoma and leiomyosarcoma, neurothecoma, gastrointestinal stromal tumor, and undifferentiated sarcoma; ⑤ Benign and malignant tumors of the urothelium; ⑥ Central nervous system tumor occurrence / recurrence; ⑦ Lymphoma / leukemia; ⑧ Endometrial intraepithelial neoplasia, endometrial carcinoma, uterine leiomyoma and leiomyosarcoma, endometrial stromal tumor; ovarian, fallopian tube, cervical, vaginal and vulvar tumors, vulvar leukoplakia; ⑨ Benign and malignant tumors of the breast, prostate, testicle, and epididymis; ⑩ Adrenal gland, some thyroid, and parathyroid tumors; Gingival tumor; (11) Inflammatory diseases: vasculitis, myocarditis with fibrosis, pneumonia, various types of hepatitis, liver fibrosis and cirrhosis, liver abscess, cholecystitis and cholangitis, hemorrhagic necrotizing pancreatitis, chronic pancreatitis and fibrosis, ulcerative colitis, glomerulonephritis, glomerular fibrosis and sclerosis, glandular cystitis, ureteritis and stenosis, non-infectious urethritis, non-infectious mastitis, uveitis, thyroiditis, neuritis and aseptic inflammation; (12) Atrophic diseases: gingival atrophy, myocardial fibrosis and atrophy, gastrointestinal mucosal glands and smooth muscle atrophy, pancreatic atrophy, bladder Atrophy of smooth muscle tissue around the eyeball, atrophy of the testicles, seminal vesicles and prostate, atrophy of squamous epithelium, and atrophy and reduction of hair follicles; (13) Proliferative diseases: nodular hyperplasia of blood vessels, hyperplasia of the endometrium, hyperplasia of the breast, sweat glands and prostate, adrenal hyperplasia; myelodysplastic syndrome and lymphoproliferative lesions; (14) Stones: urinary system stones and gallbladder biliary stones; (15) Benign polyps: fundic gland polyps, gallbladder polyps and endometrial polyps; (16) Female and male reproductive system diseases: ① Hypogonadism or hypergonadism of unknown cause; ② Amenorrhea , dysmenorrhea, female infertility, premature birth, miscarriage, intrauterine fetal death, pregnancy-induced hypertension syndrome and hydatidiform mole; ③ male infertility; (17) some fever or low body temperature; (18) mental or psychological abnormalities: bad temper, anxiety, depression and autism; (19) abnormal laboratory indicators: urine occult blood and / or urine protein (+), increased cholesterol, leukocytopenia and thrombocytopenia, increased aspartate aminotransferase AST, hypothyroidism or hyperthyroidism; (20) microscopic pathological changes: pulmonary edema, microscopic polyangiitis, protein casts in renal tubules, powdery glomeruli visible in renal capsule The following are the symptoms of renal insufficiency: (1) dilatation of renal capsule, formation of microthrombi such as microthrombi and thrombus-like substances in glomerular capillaries, local necrosis of glomeruli or proliferation and apoptosis of cells in glomeruli, infiltration of neutrophils in glomeruli, atrophy of glomeruli and renal tubules, renal interstitial edema, amyloidosis, fibrosis and calcification; (21) Others: hepatic encephalopathy, hepatorenal syndrome, nephrotic syndrome, uremia, acute lung injury or acute respiratory distress syndrome, metabolic syndrome, menopausal syndrome, Churg-Strauss syndrome and Vogt-Koyanagi-Harada syndrome.

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