阅读说明：本技术 一种具有调节血糖及血脂功能的组合物及其用途 (Composition with functions of regulating blood sugar and blood fat and application thereof ) 是由 范代娣 宇文伟刚 段志广 马晓轩 于 2020-07-16 设计创作，主要内容包括：本申请公开一种具有调节血糖及血脂功能的组合物,其中,所述组合物包含人参皂苷Rh4和冠突散囊菌；一种前述组合物在制备用于预防和/或治疗糖尿病和高血脂症两种疾病或所述两种疾病引起的并发症的制品中的用途；一种降低糖尿病及高血脂症受试者血糖和血脂的方法,包括给药受试者有效剂量的人参皂苷Rh4和冠突散囊菌；以及一种用于预防和/或治疗糖尿病和高血脂症两种疾病或所述两种疾病引起的并发症的制品,其包含有效剂量的人参皂苷Rh4和冠突散囊菌。应用本申请所提供的组合物可以充分发挥人参皂苷Rh4及冠突散囊菌在降糖、降脂方面的活性,同时可以实现两者之间的相互促进,相比于单独治疗,效果提升明显。(The application discloses a composition with the function of regulating blood sugar and blood fat, wherein the composition comprises ginsenoside Rh4 and eurotium cristatum; the use of one of the aforementioned compositions for the preparation of a product for the prevention and/or treatment of both diabetes and hyperlipidemia diseases or complications resulting from both diseases; a method for reducing blood sugar and blood lipid of subjects with diabetes and hyperlipidemia comprises administering effective dose of ginsenoside Rh4 and Eurotium cristatum to the subjects; and a product for preventing and/or treating both diabetes and hyperlipidemia or complications caused by both, which comprises effective amounts of ginsenoside Rh4 and Eurotium cristatum. The composition provided by the application can fully exert the activities of the ginsenoside Rh4 and the eurotium cristatum in the aspects of reducing blood sugar and blood fat, can realize mutual promotion between the ginsenoside Rh4 and the eurotium cristatum, and has an obvious effect improvement compared with single treatment.)

1. A composition with the function of regulating blood sugar and blood fat, which is characterized by comprising ginsenoside Rh4 and eurotium cristatum.

2. The composition of claim 1, wherein the eurotium cristatum is selected from hyphae, spores, or a combination thereof of eurotium cristatum.

3. The composition according to claim 1 or 2, wherein the eurotium cristatum is in a treated, wall-broken state or an untreated, non-wall-broken state, preferably a treated, wall-broken state.

4. The composition according to any one of claims 1 to 3, wherein the weight ratio of ginsenoside Rh4 to the eurotium cristatum is 1:1 to 1:10(w/w), preferably 1:1 to 1:5(w/w), more preferably 1:2.5 (w/w).

5. Use of a composition according to any one of claims 1 to 4 in the manufacture of a product for the prevention and/or treatment of diabetes and related disorders thereof and/or hyperlipidemia and related disorders thereof.

6. A method for reducing blood glucose and blood lipid levels in a subject with diabetes and/or hyperlipidemia comprises administering to the subject an effective amount of ginsenoside Rh4 and Eurotium cristatum.

7. An article of manufacture for the prevention and/or treatment of diabetes and related disorders thereof and/or hyperlipidemia and related disorders thereof, comprising an effective amount of the composition of any one of claims 1-4; preferably, the article of manufacture is a medicament, kit, food or health product;

preferably, the product contains 25-35 wt% of ginsenoside Rh4 and eurotium cristatum.

8. The preparation according to claim 7, further comprising pharmaceutically, nutraceutically specified adjuvants or additives or a combination of both.

9. The preparation according to claim 7 or 8, wherein the preparation is in the form of an oral preparation, injection or patch, preferably an oral preparation or injection, more preferably an oral preparation, wherein the oral preparation is a tablet, capsule, granule, suspension or pill, preferably a tablet or capsule.

10. Use of a product according to any one of claims 7 to 9 for reducing blood glucose concentration, total cholesterol, triglycerides and/or lipoprotein load in the blood.

Technical Field

The application belongs to the technical field of medicines, and particularly relates to a composition with functions of regulating blood sugar and blood fat and application of the composition in the field of preventing, relieving and treating complications caused by diabetes, hyperlipidemia or two diseases.

Background

Diabetes mellitus is a metabolic disorder syndrome associated with abnormal production and action of insulin and mainly characterized by hyperglycemia, is a chronic disease seriously harming health, and is one of the major health problems facing human beings at present. According to the latest data statistics, about 2.46 hundred million people all over the world have type II diabetes, the number of type II diabetes patients is estimated to increase to 3.8 hundred million within 20 years, the number of diabetes patients in China is up to 8000 or more than ten thousand at present, and accounts for one third of the total number of diabetes patients all over the world, so that the diabetes mellitus type II is the first major country of diabetes mellitus in the world. At present, the incidence rate of diabetes mellitus is on the rise in the world, particularly the rise in developing countries is more obvious, the mortality rate is second to cardiovascular and cerebrovascular diseases and cancers, and the diabetes mellitus is considered as the third killer of human beings. Therefore, active prevention and treatment of diabetes is urgently needed.

Hyperlipidemia is a clinical condition in which lipids in the blood are higher than normal due to abnormal fat metabolism or movement, and is usually manifested by hyperlipoproteinemia, i.e., hypercholesterolemia, hypertriglyceridemia, or both. According to the statistical result of 2013 of the Ministry of health in China, the proportion of hyperlipidemia is up to 40% in the population who is subjected to hyperlipidemia examination in the age of 15-69, and the survival rate of hyperlipidemia is 3-4 times that of the diagnosed cardiovascular and cerebrovascular disease patients. Atherosclerosis caused by hyperlipidemia is a main cause of cardiovascular and cerebrovascular diseases, in China, the incidence rate of the cardiovascular and cerebrovascular diseases is up to 8%, and on average, one person dies due to the cardiovascular and cerebrovascular diseases every 15 minutes, and a large number of studies prove that hyperlipidemia is an important cause of malignant cardiovascular and cerebrovascular diseases such as stroke, coronary heart disease, myocardial infarction, sudden death and the like. In addition, hyperlipidemia can also induce the onset of diabetes and impaired glucose tolerance, and is also an important induction factor for fatty liver, liver cirrhosis, cholelithiasis and pancreatitis, so that hyperlipidemia is prevented, relieved and treated at all times.

The existing hypoglycemic and hypolipidemic drugs have the defects that the high-efficiency drugs are accompanied with high toxic and side effects, and the high-safety drugs are not good in treatment effect in the clinical use process. Meanwhile, diabetes and hyperlipidemia belong to metabolic abnormality diseases and are mutually induced, so that hyperlipidemia patients are prone to suffer from diabetes at the same time, the diabetes patients are frequently high-incidence crowds of hyperlipidemia, and the existing first-line treatment medicine cannot give consideration to both diabetes and hyperlipidemia or has unobvious synergistic effect in treatment of diabetes and hyperlipidemia. Therefore, it is necessary to develop a drug which has high efficiency, high safety and remarkable treatment effects on diabetes and hyperlipidemia.

Patent document 1 discloses that ginsenoside Rh4, an active ingredient extracted from ginseng, a precious traditional Chinese medicine, has lipase inhibitor activity, and can inhibit triglyceride hydrolysis and reduce the intake of monoglyceride and free fatty acid, thereby achieving the effect of reducing blood fat.

Patent document 2 discloses a novel use of a secondary ginsenoside and a fatty acid ester thereof for preventing and treating diabetes, the secondary ginsenoside and the fatty acid ester thereof being capable of lowering blood sugar of a diabetic patient, improving glucose tolerance and the like, the secondary ginsenoside mainly comprising: RF1, RF3, Rh1, Mc, Mx, Rk1, Rk2, Rk3, Rh3, Rh4, Rg5, S-PPd, S-PPt, etc.

Patent document 3 discloses a health tea tablet for preventing and treating diabetes and a preparation method thereof. Is prepared from fresh leaves of Camellia Chysantha, fresh leaves of Aquilaria sinensis, immature guava, fresh leaves of green tea, Cordyceps militaris, artificially cultured shoot of Dendrobium officinale, edible grade GUANTUSAN Capsule bacterial liquid, Saccharomyces cerevisiae bacterial liquid, and pullulan. Has the characteristics of obvious blood sugar reduction, diabetes prevention, good flavor and taste and the like.

Disclosure of Invention

In order to solve the defects that the treatment medicines in the prior art cannot give consideration to diabetes and hyperlipidemia or have unobvious synergistic effect, high-efficiency medicines are accompanied with high toxic and side effects, high-safety medicines are poor in treatment effect, and the like, the application provides a composition with the function of regulating blood sugar and blood fat and application thereof. The ginsenoside Rh4 and the eurotium cristatum are combined in a certain proportion, so that the composition has good effects of resisting sugar and reducing blood fat, and compared with respective effects, the effects of reducing sugar and reducing blood fat of the composition are obviously improved, and the composition is good in safety and has good medicinal prospects.

The specific technical scheme of the application is as follows:

1. a composition with the function of regulating blood sugar and blood fat, which is characterized by comprising ginsenoside Rh4 and eurotium cristatum.

2. The composition of item 1, wherein the Eurotium cristatum is selected from hyphae, spores, or a combination thereof.

3. The composition according to item 1 or 2, wherein the Eurotium cristatum is in a treated wall-broken state or an untreated non-wall-broken state, preferably a treated wall-broken state.

4. The composition according to any one of items 1 to 3, wherein the weight ratio of ginsenoside Rh4 to the eurotium cristatum is 1:1 to 1:10(w/w), preferably 1:1 to 1:5(w/w), and more preferably 1:2.5 (w/w).

5. Use of the composition according to any one of items 1 to 4 in the preparation of an article for the prevention and/or treatment of diabetes and related disorders thereof and/or hyperlipidemia and related disorders thereof.

6. A method for reducing blood glucose and blood lipid levels in a subject with diabetes and/or hyperlipidemia comprises administering to the subject an effective amount of ginsenoside Rh4 and Eurotium cristatum.

7. An article of manufacture for preventing and/or treating diabetes and its related disorders and/or hyperlipidemia and its related disorders, comprising an effective amount of the composition according to any one of items 1 to 4; preferably, the article of manufacture is a medicament, kit, food or health product;

preferably, the product contains 25-35 wt% of ginsenoside Rh4 and eurotium cristatum.

8. The preparation according to claim 7, further comprising pharmaceutically, nutraceutically specified adjuvants or additives or a combination of both.

9. The article of manufacture of claim 7 or 8, wherein the pharmaceutical dosage form is an oral formulation, an injection or a patch, preferably an oral formulation or an injection, more preferably an oral formulation, wherein the oral formulation is a tablet, a capsule, a granule, a suspension or a pill, preferably a tablet or a capsule.

10. Use of a product according to any of items 7 to 9 for reducing blood glucose concentration, total cholesterol, triglycerides and/or lipoprotein load in blood.

Effect of application

(1) The active monomer ginsenoside Rh4 in the natural traditional Chinese medicine ginseng is compatible with the hypha form or the spore form of the probiotic eurotium cristatum, so that the effects of reducing blood sugar and blood fat are achieved; (2) the composition containing the ginsenoside Rh4 and the probiotic eurotium cristatum in the proportion is remarkably improved in the effects of reducing blood sugar and blood fat; (3) the composition provided by the application can fully exert the activities of the ginsenoside Rh4 and the eurotium cristatum in the aspects of reducing blood sugar and blood fat, can realize mutual promotion between the ginsenoside Rh4 and the eurotium cristatum, and has an obvious effect improvement compared with single treatment; (4) this application can realize that a medicine treats more, can reduce the type of taking medicine that has diabetes, hyperlipemia patient simultaneously, and the doctor of reinforcing patient follows the nature, makes things convenient for the patient to take medicine.

Detailed Description

The present application will be described in detail below.

It is to be understood that throughout the specification and claims, the terms "including" and "comprising" are used in an open-ended fashion, and thus should be interpreted to mean "including, but not limited to. The description which follows is a preferred embodiment of the invention, but is made for the purpose of illustrating the general principles of the invention and not for the purpose of limiting the scope of the invention. The scope of the present invention is defined by the appended claims.

Definition of

"ginsenoside" is a steroid compound, mainly present in ginseng, which can participate in multiple metabolic pathways, so its potency is also complex. "ginsenoside Rh 4", molecular formula: c₃₆H₆₀O₈The molecular weight is 620.4, the scientific name is 6-O- β -D-glucopyranosyl-20(-HO) -trans-protopanaxatriol, the odorless white powder is soluble in methanol and ethanol, slightly soluble in ethyl acetate and insoluble in trichloromethane and diethyl ether, the CAS number is 174721-08-5, and the structure is shown as the formula (I):

the eurotium cristatum belongs to Aspergillus glaucus, and is widely distributed, and the growth substrate comprises soil, Fuzhuan tea, Cordyceps sinensis, Chinese medicinal tablet and sawdust. The eurotium cristatum consists of ascocarp and hypha, wherein the ascocarp is a yellow spherical or approximately spherical closed ascocarp shell, the diameter of the ascocarp shell is about 150-200 mu m, the ascocarp is broken to release spherical, approximately spherical or biconvex lens-shaped ascospores with the diameter of 5 mu m, and the ascocarp shell has a crown-shaped protrusion with the width of about 0.8-1.0 mu m; the hyphae have a diameter of about 8-10 μm, are white and belong to eurotium cristatum. The strain belongs to the genus Aspergillus of the anamorph genus, called as Microcorolla, and is a synbiotics strain. Producing sexual spores under the induction of low osmotic pressure, producing asexual spores under the induction of high osmotic pressure, and producing asexual spores under the induction of high osmotic pressure.

Diabetes mellitus is a series of metabolic disorder syndromes of sugar, protein, fat, water, electrolyte and the like caused by hypofunction of pancreatic islets, insulin resistance and the like due to the action of various pathogenic factors such as genetic factors, immune dysfunction, microbial infection and toxins thereof, free radical toxins, mental factors and the like on organisms, and is clinically characterized by hyperglycemia.

"diabetic complications" are damage or dysfunction of other organs or tissues of the body caused by poor blood glucose control during diabetes, including damage or dysfunction of the liver, kidney, heart, retina, nervous system, etc. According to the statistics of the world health organization, the diabetes complications are more than 100, and are the most known diseases at present.

"blood lipids" are a generic term for triglycerides, cholesterol, phospholipids, and non-lipidated fatty acids, and the like. Blood lipids are insoluble in water and must be combined with a specific class of proteins in the blood to form lipoproteins, "lipoprotein loading" refers to the total amount of blood lipids carried in such proteins.

"hyperlipidemia" refers to a pathological condition in which the blood lipid components such as cholesterol, triglyceride, phospholipid and non-lipidated fatty acids in plasma are increased.

"hyperlipidemia" is a clinical symptom in which lipids in blood are higher than normal levels due to abnormal fat metabolism or operation, and is also referred to as "hyperlipidemia" or "dyslipidemia". Lipids in blood such as Triglyceride (TG), Free Cholesterol (FC), Cholesterol Ester (CE), and phospholipid are rarely soluble in water, and only form a macromolecular complex (lipoprotein) with Apolipoprotein (APO) can be dissolved, transported, and metabolized in the blood, so hyperlipidemia is usually manifested as hyperlipoproteinemia, i.e., hypercholesterolemia, hypertriglyceridemia, or both. Hyperlipidemia is generally characterized by the fact that the fasting blood triglyceride of an adult exceeds 160mg/dl, the cholesterol exceeds 260mg/dl and the cholesterol of a child exceeds 160 mg/dl. Because of the differences in the types of blood lipids or lipoproteins, the types of blood lipids or lipoproteins outside the normal range can also be different, the World Health Organization (WHO) classifies hyperlipoproteinemia into five types: type I, mainly increased chylomicron, milky white turbid serum, containing a large amount of Triglyceride (TG); type II, which is divided into type IIa and type IIb, wherein the former mainly has obviously increased Low Density Lipoprotein (LDL), and the latter has also increased Very Low Density Lipoprotein (VLDL); type III, increasing serum turbid LDL and VLDL, and fusing the two on electrophoresis; form IV, predominantly VLDL increased, serum or turbid; form V, chylomicron and VLDL were increased, and the serum was milky white. Of these, the types II and IV are most common.

"hyperlipidemia-associated condition" refers to a condition whose cause, pathogenesis, pathological manifestations, clinical symptoms, and/or therapeutic principle are related to hyperlipidemia. Preferably, the disorder includes, but is not limited to, diabetes, hypertension, atherosclerosis, coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, chronic hepatitis, fatty liver, liver cirrhosis, cerebral ischemia, cerebral infarction, chronic nephritis, chronic pyelonephritis, renal insufficiency, nephrotic syndrome, uremia, obesity.

"Low-density lipoprotein cholesterol" (LDL-C), is the cholesterol in low-density lipoprotein (LDL) and reflects how much of the low-density lipoprotein is.

"high density lipoprotein cholesterol" (HDL-C) is the cholesterol in High Density Lipoprotein (HDL), which reflects the amount of high density lipoprotein.

Superoxide Dismutase (SOD) is an antioxidant metalloenzyme existing in organisms, can catalyze Superoxide anion free radical disproportionation to generate oxygen and hydrogen peroxide, plays a vital role in the balance of oxidation and antioxidation of organisms, and is inseparable from the occurrence and development of a plurality of diseases.

"effective dose" refers to the dose used when the drug is a pharmaceutical product that exerts its pharmaceutical function; the dosage corresponding to the desired function when used as a health product or a functional food can be obtained by a person skilled in the art in a limited number of experiments according to actual needs.

The application provides a composition with the function of regulating blood sugar and blood fat, which comprises ginsenoside Rh4 and eurotium cristatum.

The ginsenoside Rh4 and the eurotium cristatum have the effects of reducing blood sugar and blood fat, and the active monomer ginsenoside Rh4 in the natural traditional Chinese medicine ginseng is combined with the probiotic eurotium cristatum to achieve good effects of reducing blood sugar and blood fat.

In a specific embodiment, the blood glucose is selected from one or more of the following: serum glucose levels, serum fructosamine levels, serum glycated hemoglobin levels. In another specific embodiment, the blood glucose is serum glucose level. In the above specific embodiments, the diabetes is type I diabetes (T1DM) or type II diabetes (T2 DM).

In a specific embodiment, the blood lipid is selected from one or more of the following: cholesterol, triglycerides, phospholipids, non-lipidated fatty acids.

In one embodiment, the ginsenoside Rh4 is naturally extracted. Specifically, the ginsenoside Rh4 can be extracted from one or more of wild ginseng, garden ginseng, American ginseng, pseudo-ginseng, red ginseng and white ginseng.

In one embodiment, ginsenoside Rh4 can be obtained by water extraction, organic solvent extraction, osmosis, distillation, ultrasonic impregnation, extraction, macroporous adsorbent resin separation techniques, or a combination thereof.

In one embodiment, eurotium cristatum may be derived from soil, Fuzhuan tea, Cordyceps sinensis, Chinese medicinal tablet or wood dust, etc. Preferably, the eurotium cristatum is derived from Fuzhuan tea.

In one embodiment, the Eurotium cristatum can be hyphae of Eurotium cristatum, spores of Eurotium cristatum, or a combination of hyphae and spores of Eurotium cristatum. The hypha and spore can be prepared from Eurotium cristatum by large-scale fermentation culture.

In one embodiment, the Eurotium cristatum may be in a wall-broken state in which the cell wall morphology is broken by physical, biological or chemical means to release the intracellular contents, or in an untreated non-wall-broken state. Preferably in a treated, wall-broken state. The physical, biological and chemical methods for breaking cell walls refer to the common wall breaking methods of the technicians in the field, such as: high-pressure homogenizing, ultrasonic wall breaking, biological enzyme wall breaking, acid-base wall breaking, etc.

In a specific embodiment, the weight ratio of ginsenoside Rh4 to the eurotium cristatum is 1:1 to 1:10(w/w), and may be, for example, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, 1:10 (w/w); preferably 1:1 to 1:5(w/w), more preferably 1:2.5 (w/w).

The application also provides application of the composition containing the ginsenoside Rh4 and eurotium cristatum in preparing products for preventing and/or treating diabetes and related diseases and/or hyperlipidemia and related diseases.

In one embodiment, the article of manufacture may be a pharmaceutical, a kit, a nutraceutical, or a functional food.

In one embodiment, the product comprises 25-35 wt% of ginsenoside Rh4 and eurotium cristatum, and specifically may be 25 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, 30 wt%, 31 wt%, 32 wt%, 33 wt%, 34 wt%, 35 wt% of ginsenoside Rh4 and eurotium cristatum.

In one embodiment, the article of manufacture is a medicament, which may be administered in combination with one or more other medicaments or methods of treatment.

The present application also provides a method of lowering blood glucose and blood lipids in a subject with diabetes and/or hyperlipidemia comprising administering to the subject an effective amount of a composition comprising ginsenoside Rh4 and eurotium cristatum as described previously.

In a specific embodiment, the subject has diabetes or diabetes and its related conditions; in one embodiment, the subject has hyperlipidemia or hyperlipidemia and related conditions; in a specific embodiment, the subject has both diabetes and hyperlipidemia.

In a specific embodiment, the composition containing ginsenoside Rh4 and Eurotium cristatum can promote the expression and/or secretion of insulin and simultaneously reduce the expression and/or secretion of glucagon in a subject, and specifically, the composition containing ginsenoside Rh4 and Eurotium cristatum can promote the expression and/or secretion of insulin and simultaneously reduce the expression and/or secretion of glucagon in the subject and lower the blood sugar of the subject to realize that the blood sugar of the subject returns to normal or close to normal level.

The present application also provides a method of reducing the risk of atherosclerosis in a subject comprising administering to the subject an effective amount of ginsenoside Rh4 and eurotium cristatum. The application also provides the use of ginsenoside Rh4 and eurotium cristatum for reducing the risk of atherosclerosis in a subject. The invention also relates to the use of ginsenoside Rh4 and Eurotium cristatum in the preparation of a product for reducing the risk of atherosclerosis in a subject.

The present application also provides an article of manufacture for the prevention and/or treatment of diabetes and its related disorders and/or hyperlipidemia and its related disorders, characterized in that it comprises an effective amount of the aforementioned composition. Preferably, the article of manufacture is a pharmaceutical, kit, food or nutraceutical.

In one embodiment, the preparation contains the composition, and pharmaceutically acceptable adjuvants and nutritionally acceptable additives according to the preparation.

In a specific embodiment, the hyperlipidemia is selected from one or more of: hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and hypo-high density lipoproteinemia.

In one embodiment, pharmaceutically acceptable adjuvants include pharmaceutically acceptable carriers, excipients, diluents, and the like, which are compatible with the active ingredient. The use of pharmaceutically acceptable adjuvants for the preparation of pharmaceutical formulations is well known to those of ordinary skill in the art, and the compositions herein combine the active ingredient and pharmaceutically acceptable adjuvants to form a variety of formulations, preferably solid and liquid formulations, more preferably solid formulations. The formulations of the present application may be in unit dosage forms such as tablets, pills, capsules (including sustained release or delayed release forms), powders, suspensions, granules, tinctures, syrups, emulsions, suspensions and various sustained release formulations. Preferably, the medicament is an oral pharmaceutical preparation or an injection, such as a granule, tablet, pill and/or capsule, most preferably a tablet or capsule.

The present application also provides the use of a product as described above for reducing blood glucose concentration, total cholesterol, triglycerides and/or lipoprotein load in the blood.

The composition of the ginsenoside Rh4 and the eurotium cristatum has good effects of reducing blood sugar and blood fat; the ratio of the ginsenoside Rh4 to the probiotic eurotium cristatum is further limited, the effects of reducing blood sugar and blood fat of the composition can be further highlighted, the composition and the product thereof fully exert the activities of the ginsenoside Rh4 and the eurotium cristatum in the aspects of reducing blood sugar and blood fat, compared with single treatment, the synergistic effect of the ginsenoside Rh4 and the eurotium cristatum is obviously improved, and the composition has good treatment and health-care effects on patients suffering from diabetes and hyperlipidemia simultaneously.