WO2019201315A1 - Composition contenant de la phlorizine et de la 1-désoxynojirimycine, et utilisation de celle-ci - Google Patents
Composition contenant de la phlorizine et de la 1-désoxynojirimycine, et utilisation de celle-ci Download PDFInfo
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- WO2019201315A1 WO2019201315A1 PCT/CN2019/083293 CN2019083293W WO2019201315A1 WO 2019201315 A1 WO2019201315 A1 WO 2019201315A1 CN 2019083293 W CN2019083293 W CN 2019083293W WO 2019201315 A1 WO2019201315 A1 WO 2019201315A1
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- WO
- WIPO (PCT)
- Prior art keywords
- phlorizin
- deoxynojirimycin
- active ingredient
- mice
- composition
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to the fields of medicine, health care products and foods, and in particular to compositions comprising phlorizin and 1-deoxynojirimycin, and to the use of said compositions for lowering blood glucose.
- Diabetes Mellitus is a series of clinical syndromes caused by absolute or relative deficiency of insulin in the body.
- the disease can also cause complications in the development process, such as: Hypoglycemia, Ketoacidosis, Nonketotic Hyperosmolar Coma, Cardiovascular Disease, Chronic Renal Failure, Retinopathy, neuropathy and microvascular disease.
- drugs for diabetes treatment include: biopharmaceuticals such as insulin (Insulin); chemical drugs such as Sulfonylurea, Biguanide, Glitazone; and natural drugs such as Chinese herbal medicine.
- biopharmaceuticals such as insulin (Insulin); chemical drugs such as Sulfonylurea, Biguanide, Glitazone; and natural drugs such as Chinese herbal medicine.
- injectable drugs such as Glucagon-like peptide (GLP-1), fatty acylated glucagon-like polypeptide (NN2211, Novo Nordisk), Exendin-4 (Amylin) and poly Ethylene glycol-modified Exendin-4, etc.
- GLP-1 Glucagon-like peptide
- N2211 fatty acylated glucagon-like polypeptide
- Exendin-4 Amylin
- poly Ethylene glycol-modified Exendin-4 etc.
- DPP-IV inhibitors because of their inhibitory effects on a large class of enzymes in the body, will change the distribution of body fat, and the actual effect of administration is relatively poor.
- various proprietary Chinese medicines for treating diabetes have certain therapeutic effects, it is difficult to ensure the efficacy of the drug and the quality of the drug because the mechanism of action of the drug alone or its mechanism of action and active ingredients are still unclear.
- a first aspect of the invention provides a composition of a natural hypoglycemic active ingredient, the composition comprising a first component and a second component, wherein:
- the first component is selected from the group consisting of: phlorizin, a plant extract containing phlorizin, or a plant raw material containing phlorizin or a processed plant material;
- the second component is selected from the group consisting of 1-deoxynojirimycin, a plant extract containing 1-deoxynojirimycin, or a plant material containing 1-deoxynojirimycin or a processed plant material.
- hypoglycemic active ingredient composition has a total weight of phlorizin and 1-deoxynojirimycin of 50 to 1000 mg/g.
- the total weight of phlorizin and 1-deoxynojirimycin is 100 to 980 mg/g.
- hypoglycemic active ingredient composition has a total weight of phlorizin and 1-deoxynojirimycin of 300 to 980 mg/g.
- the hypoglycemic active ingredient composition is composed of a turmeric leaf containing phlorizin and a mulberry leaf containing 1-deoxynojirimycin, and a dry weight ratio of the leaves of the wood ginger leaf and the mulberry leaf For: 1-100: 1-100.
- hypoglycemic active ingredient composition is composed of phlorizin-containing Hubei sea bream leaves and mulberry leaves containing 1-deoxynojirimycin, and the dry weight ratio of the sea otter leaves and mulberry leaves in Hubei. For: 1-100: 1-100.
- the composition is used in an amount such that the total mass of phlorizin and 1-deoxynojirimycin in the composition is ⁇ 400 mg/kg body weight (preferably, ⁇ 103 mg/kg body weight).
- the composition is used in an amount such that the quality of phlorizin in the composition is ⁇ 300 mg/kg body weight (preferably, ⁇ 100 mg/kg body weight).
- the composition is used in an amount such that the mass of 1-deoxynojirimycin in the composition is ⁇ 100 mg/kg body weight (preferably, ⁇ 10 mg/kg body weight; more preferably, ⁇ 3 mg/kg body weight) ).
- a second aspect of the invention provides the use of a hypoglycemic active ingredient composition according to the first aspect of the invention for use in the preparation of an animal for use in (i) lowering blood glucose, and/or (ii) Foods, health products and medicines that prevent and/or treat the function of diabetes and its complications.
- the composition is used for the preparation of foods, health supplements and applications for humans having (i) lowering blood glucose, and/or (ii) preventing and/or treating diabetes and its complications. / or drugs.
- a method of (i) lowering blood glucose, and/or (ii) preventing and/or treating diabetes and its complications comprising the steps of: administering to a subject in need as in the first aspect A composition of the natural hypoglycemic active ingredient.
- the subject is an animal; preferably, a mammal; more preferably, a human.
- Figure 1 is a graph showing blood glucose levels of each group at each time point after single oral phlorizin C57BL/6J mice were given sugar.
- Figure 2 is a graph showing the area under the blood glucose curve of each group at each time point after a single oral phlorizin C57BL/6J mouse.
- Fig. 3 is a graph showing blood glucose levels of each group at a time point after single oral administration of 1-deoxynojirimycin C57BL/6J mice to starch.
- Figure 4 is a graph showing the area under the blood glucose curve of each group at each time point after a single oral administration of 1-deoxynojirimycin C57BL/6J mice.
- Fig. 5 is a graph showing the blood glucose levels of each group of C57BL/6J mice given starch at various time points by a single oral phlorizin and 1-deoxynojirimycin group.
- Fig. 6 is a graph showing the area under the blood glucose curve of each group of C57BL/6J mice given starch at each time point by a single oral phlorizin and 1-deoxynojirimycin group.
- Figure 7 is a graph showing blood glucose levels of each group at each time point after administration of a single oral phlorizin to C57BL/6J mice.
- Figure 8 is a graph showing the area under the blood glucose curve of each group at each time point after administration of a single oral phlorizin to C57BL/6J mice.
- Figure 9 is a graph showing the blood glucose levels of each group at each time point after administration of 1-deoxynojirimycin to C57BL/6J mice.
- Figure 10 is a graph showing the area under the blood glucose curve of each group at each time point after administration of 1-deoxynojirimycin to C57BL/6J mice.
- Figure 11 is a graph showing the blood glucose levels of each group of C57BL/6J mice at various time points after administration of a single oral phlorizin and 1-deoxynojirimycin group.
- Figure 12 is a graph showing the area under the blood glucose curve of each group at each time point after administration of a single oral phlorizin and 1-deoxynojirimycin to the C57BL/6J mice.
- Figure 13 is a graph showing blood glucose levels of each group at each time point after a single oral sweet tea extract was administered to C57BL/6J mice.
- Figure 14 is a graph showing the area under the blood glucose curve of each group at each time point after a single oral sweet tea extract was administered to C57BL/6J mice.
- Fig. 15 is a graph showing blood glucose levels of each group at each time point after administration of a single oral mulberry leaf extract to C57BL/6J mice.
- Figure 16 is a graph showing the area under the blood glucose curve of each group at each time point after a single oral mulberry leaf extract was administered to C57BL/6J mice.
- Fig. 17 is a graph showing the blood glucose levels of each group at each time point after administration of a single oral sweet tea and mulberry leaf extract to C57BL/6J mice.
- Figure 18 is a graph showing the area under the blood glucose curve of each group at each time point after administration of a single oral sweet tea and mulberry leaf extract to C57BL/6J mice.
- the present inventors have unexpectedly discovered a safe and effective natural hypoglycemic active ingredient composition formulation containing phlorizin and 1-deoxynojirimycin. Compared with phlorizin or 1-deoxynojirimycin alone, the amount of the composition of the present invention is significantly reduced when the same hypoglycemic effect is achieved; while taking phlorizin and 1-deoxygenation at a dose containing no significant hypoglycemic effect The inoculant has completed the present invention on the basis of which the valinomycin produces a significant hypoglycemic effect.
- Phlorizin English name: Phloridzin; Molecular formula: C 21 H 24 O 10 ; Molecular weight: 436.41g / moL, soluble in hot water and ethanol, slightly soluble in cold water, insoluble in ether, chloroform, phloridzin structure As shown in formula (a).
- Phlorizin is a glucoside of phloretin, a dihydrochalcone of flavonoids, a natural dual sodium-dependent glucose transporter (SGLT-1 and SGLT-2) inhibitor that reduces intestinal glucose Into the blood and inhibit the reabsorption of glucose by the renal tubules, so that the excessive concentration of glucose in the blood is discharged from the urine, thereby lowering blood sugar.
- Phlorizin can be extracted from natural plants or medicinal materials containing phlorizin (for example, plants such as wood ginger leaf, apple tree, and sea otter).
- 1-deoxynojirimycin English name: 1-deoxynojirimycin; molecular formula: C 6 H 13 NO 4 ; molecular weight: 163.17; CAS number: 19130-96-2; soluble in water, dimethyl sulfoxide, methanol.
- 1-deoxynojirimycin is found in mulberry, comfrey, hyacinth and ginseng plants.
- 1-deoxynojirimycin is a natural alpha-glucosidase inhibitor that delays the breakdown of starch in food into glucose in the intestine. Its structural formula is as shown in formula b.
- extract or "plant extract” refers to an active ingredient (eg, 1-deoxynojirimycin or phlorizin) obtained from a plant using a conventional extraction method such as solvent extraction or the like. substance.
- the extract or plant extract can be obtained commercially, or can be prepared according to a conventional method, or can be prepared by referring to the preparation method provided herein.
- the terms "root extract containing phlorizin” and "plant extract containing phlorizin” are used interchangeably to refer to plants containing phlorizin (eg, wood ginger leaf, apple tree, Hubei sea bream). Or a certain part of the plant (for example, wood ginger leaf Ke leaves, Hubei sea bream leaves) as a raw material, the phlorizin-containing substance is obtained by a conventional method. Preferably, it is an alcohol extract.
- the content of phlorizin (mass fraction) is ⁇ 10% (preferably, 20 to 99%; more preferably, 20-50%; most Good place, 30 ⁇ 6% (30 ⁇ 3%)).
- extract containing 1-deoxynojirimycin and "plant extract containing 1-deoxynojirimycin” are used interchangeably and refer to plants containing 1-deoxynojirimycin (eg, , mulberry tree, comfrey, hyacinth, and genus of the genus) or a part of the plant as a raw material, and a substance containing 1-deoxynojirimycin is obtained.
- the content (mass fraction) of 1-deoxynojirimycin is ⁇ 5%; preferably, about 5-80%; more preferably, about 5-30%; optimally, 10 ⁇ 3% (10 ⁇ 1%).
- the preparation method of the extract containing phlorizin is not particularly limited. can use.
- the extract can be obtained by a conventional method using wood ginger leaf, apple tree, Hubei sea bream or a part thereof (for example, wood ginger leaf) as a raw material.
- an extract containing phlorizin is obtained by a solvent extraction method.
- the solvent is an alcohol solvent, more preferably ethanol.
- plantin material or processed plant material containing phlorizin means the original plant containing phloridzin or a part thereof, or the original plant having the phlorizin or a certain thereof The processed product of the part.
- the original plant containing phlorizin comprises: wood ginger leaf, apple tree and/or Hubei sea bream.
- plant material containing 1-deoxynojirimycin or processed plant material means an original plant containing 1-deoxynojirimycin or a part thereof, or the phlorizin A processed product of the original plant or a part thereof.
- the original plant containing 1-deoxynojirimycin comprises: mulberry, comfrey, hyacinth and ginseng.
- prevention refers to various means or measures for preventing the occurrence or development of a disease, including medical, physical or chemical means, to prevent and reduce various diseases before the disease is not recognized by clinical standards. The occurrence or development of symptoms.
- the term "preventing diabetes” means that the composition of the present invention is used for a clinical patient who has not yet met the "diabetes” clinical index, and will gradually develop into a potential patient clinically defined as “diabetes” over time. Improve the tolerance of these patients to glucose, promote the body's ability to glucose metabolism, and increase the body's sensitivity to insulin. Such potential patients often have "metabolic Syndrome” such as obesity, insulin resistance, glucose intolerance, hypertension, antherosclerosis, dyslipidemia (ie, in the blood). The level of triglyceride is high, and high-density lipoprotein is low at the same time.
- treating refers to the prevention and suppression of the development or progression of a disease, which inhibits, inhibits, alleviates, ameliorates, slows, stops, delays or reverses the progression of the disease. / or various indicators of disease, disorder, or pathological state at the time of administration include alleviating or reducing symptoms or complications, or curing or eliminating a disease, disorder, or condition.
- treating diabetes refers to the use of the compositions of the invention in patients clinically diagnosed as "diabetes", improving their tolerance to glucose, promoting the body's ability to glucose metabolism, and increasing the body's sensitivity to insulin. Sex, which in turn allows the patient's postprandial and fasting blood glucose to be controlled at normal levels. As the ability to glucose metabolism is increased, the occurrence and development of various cardiovascular diseases, chronic renal failure, retinopathy, neuropathy and microangiopathy caused by long-term hyperglycemia are alleviated.
- the term "food product” refers to a single compound or composition comprising the various compounds, compositions or extracts provided herein that are made edible.
- the production and manufacture of such a single compound or composition should be in accordance with relevant food safety standards, but such food safety standards must not limit the invention.
- the term "health product” means that a single compound or composition comprising the various compounds, compositions or extracts provided by the present invention is prepared for administration to a patient for the prevention and treatment of the disease. purpose. It pertains to the term food as used herein, but it should also be produced, manufactured and sold in accordance with various related requirements, standards and specifications.
- drug refers to a single compound that can be used to prevent or treat a disease, a composition formed from a plurality of compounds, a plant or a Chinese medicinal material and an extract thereof, or a single compound as a main active ingredient.
- a composition or formulation also refers to a composition or formulation comprising a plurality of compounds as active ingredients.
- “Drug” should be understood to refer not only to the products approved and approved for production by the administrative agencies established by the laws of a country, but also to the inclusion of a single compound as an active ingredient in order to obtain approval and approval of production.
- “Formation” is understood to mean obtained by chemical synthesis, biotransformation or purchase.
- the present invention provides a composition of a natural hypoglycemic active ingredient comprising a first component and a second component, wherein:
- the second component is selected from the group consisting of 1-deoxynojirimycin, a plant extract containing 1-deoxynojirimycin, or a plant material containing 1-deoxynojirimycin or a processed plant material.
- a composition of natural hypoglycemic active ingredients wherein the total weight of phlorizin and 1-deoxynojirimycin is 50-1000 mg/g; that is, per gram of the composition of the natural hypoglycemic active ingredient, phlorizin and 1
- the total weight of deoxynojirimycin is 50 to 1000 mg.
- the total weight of phlorizin and 1-deoxynojirimycin is 300 to 980 mg/g.
- the composition consists of Hubei sea bream leaves containing phlorizin and mulberry leaves containing 1-deoxynojirimycin, and the ratio of dry weight of sea otter leaves to mulberry leaves is 1-100. : 1-100.
- the amount of the composition is the total mass of phlorizin and 1-deoxynojirimycin in the composition ⁇ 400 mg / kg body weight (preferably, ⁇ 103 mg / kg body weight) .
- the amount of the composition is the mass of phlorizin in the composition ⁇ 300 mg / kg body weight (preferably, ⁇ 100 mg / kg body weight).
- the amount of the composition is the mass of 1-deoxynojirimycin in the composition ⁇ 100 mg / kg body weight (preferably, ⁇ 10 mg / kg body weight; more preferably, ⁇ 3mg / kg body weight).
- the composition is an extract composition, that is, the first component of the composition is a plant extract containing phlorizin, and the second component is a 1-deoxynojirimycin Plant extract.
- the first component has a phlorizin content of 30 ⁇ 6 wt% and the second component has a 1-deoxynojirimycin content of 10 ⁇ 3 wt%.
- the mass ratio of the first component to the second component is (10 to 100):1.
- the pharmaceutical excipient may also be an excipient used for achieving a specific administration purpose or manner (for example, sustained release administration, controlled release administration, pulse administration, etc.) (for example, but not limited to, gelatin, Albumin, chitosan, polyether and polyester polymer materials such as polyethylene glycol, polyurethane, polycarbonate and copolymers thereof.
- a specific administration purpose or manner for example, sustained release administration, controlled release administration, pulse administration, etc.
- the main manifestations of facilitating administration include, but are not limited to, improving therapeutic effects, improving bioavailability, reducing toxic side effects, and improving patient compliance.
- the pharmaceutical composition of the present invention can also be prepared into a dosage form which is advantageous for administration by a conventional method; the dosage form includes, but is not limited to, a water pill, a powder, a tablet, a granule, a capsule, a sustained release agent, and a controlled release. Agents, etc.
- Excipients for the preparation of oral liquid preparations generally include: a solvent, and optionally flavoring, bacteriostatic, emulsifying, and coloring agents.
- Excipients for preparing tablets generally include fillers (eg, starch, powdered sugar, dextrin, lactose, compressible starch, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, mannitol, etc.), binders (eg, ethanol, starch slurry, sodium carboxymethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, gelatin solution, sucrose solution, and aqueous solution of polyvinylpyrrolidone Or alcohol solution, etc.), disintegrants (eg, dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone and croscarmellose sodium) and lubricants (eg: Magnesium stearate, micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycol 4,000, polyethylene glycol 6,000, magnesium lauryl s
- the use of the hypoglycemic active ingredient composition is to prepare a food, health care product for humans having (i) lowering blood glucose, and/or (ii) preventing and/or treating diabetes and its complications. Products and drugs.
- the invention also provides a method of (i) lowering blood glucose, and/or (ii) preventing and/or treating diabetes and its complications, comprising the steps of:
- safety and effective amount means that the amount of the active ingredient (i.e., phlorizin and 1-deoxynojirimycin) is sufficient to significantly improve the condition of diabetes and/or lower blood sugar without causing serious side effects.
- composition delays the digestion of food to produce glucose and reduces the absorption of glucose; when the blood glucose concentration is too high, the blood glucose is discharged from the urine, and the blood sugar is more effectively maintained at a normal level.
- the mulberry leaf extract containing 1-deoxynojirimycin was purchased from Shanghai Ziishi Biotechnology Co., Ltd. (1-deoxynojirimycin content was 10.1%); 1-deoxygen used The pure scorpionmycin was purchased from Chengdu Pusi Biotechnology Co., Ltd. (content >99%).
- Example 1 Preparation of phlorizin and extracts containing phlorizin plant
- the phlorizin and 1-deoxynojirimycin crystals were weighed separately and mixed according to the ratio of 100:0.3, 100:1, 100:3, 20:1, 10:1, 5:1 and 3:1 by weight. Water is dissolved for intragastric administration.
- Example 3 Preparation of a plant extract containing phlorizin and a composition containing 1-deoxynojirimycin plant extract
- mice 21 C57BL/6J mice (8-10 weeks old, gender: male, body weight 18-22 g, purchased from Shanghai Lingchang Biological Co., Ltd.).
- mice were hungry for 12 hours, free to drink water, and were randomly divided into 3 groups according to body weight and starvation blood glucose.
- the mice were intragastrically administered, and 15 g after the administration, 3 g/kg of glucose was administered by gavage, and blood glucose was measured before, after, 30, 30, 60, 90, and 2 h, and the administration time, body weight, and blood glucose were recorded.
- Table 1 The effect of single intragastric administration of phlorizin on oral glucose tolerance (mmol/L) in normal C57BL/6J mice is shown in Table 1.
- mice were starved for 12 hours, free to drink water, and were randomly divided into 5 groups according to body weight and starvation blood sugar.
- the mice were intragastrically administered, and 15 g after administration, 3 g/kg of starch was administered by gavage, and blood glucose was measured before, after, 30, 30, 60, 90, and 2 h of starch, and the administration time, body weight, and blood glucose were recorded.
- the effect of a single intragastric administration of deoxynojirimycin (DNJ) on oral glucose tolerance (mmol/L) in normal C57BL/6J mice is shown in Table 2.
- DNJ deoxynojirimycin
- test substance 1-deoxynojirimycin is intragastrically administered to the starch 15 minutes after a single administration, and the blood glucose of the mouse after oral administration of the starch can be reduced in a dose-dependent manner at 15 min and 30 min.
- the lower area also showed a dose-dependent change at each time point, with an effective dose of 15 mg/kg or less.
- mice 40 C57BL/6J mice (8-10 weeks old, gender: male, body weight 18-22 g, purchased from Shanghai Lingchang Biological Co., Ltd.).
- mice were starved for 12 hours, free to drink water, and were randomly divided into 5 groups according to body weight and starvation blood sugar.
- the mice were intragastrically administered, and 15 g after administration, 3 g/kg of starch was administered by gavage, and blood glucose was measured before, after, 30, 30, 60, 90, and 2 h of starch, and the administration time, body weight, and blood glucose were recorded.
- the effect of a single intragastric administration of deoxynojirimycin on oral glucose tolerance (mmol/L) in normal C57BL/6J mice is shown in Table 3.
- mice 16 C57BL/6J mice (8-10 weeks old, gender: male, body weight 18-22 g, purchased from Shanghai Lingchang Biological Co., Ltd.).
- mice were starved for 12 hours, free to drink water, and were randomly divided into 2 groups according to body weight and starvation blood glucose.
- the mice were intragastrically administered, and 15 g after the administration, 3 g/kg of starch was intragastrically administered, and blood glucose was measured before, after, 30, 30, 60, 90, and 2 h of the starch, and the administration time, body weight, and blood glucose were recorded.
- the effect of single gavage administration of phloridin (Phl) on oral glucose tolerance (mmol/L) in normal C57BL/6J mice is shown in Table 4.
- test substance phlorizin is administered to the starch by intragastric administration 15 minutes after a single administration, and the test group phlorizin 100 mg/kg dose group is orally administered with sugar tolerance to normal mice. There were no significant changes (see Table 4, Figure 7, and Figure 8).
- the results of the comprehensive example 4 suggest that the mice were orally administered with starch or glucose, and the dose of phlorizin 100 mg/kg did not show significant hypoglycemic effect.
- mice 40 C57BL/6J mice (8-10 weeks old, gender: male, body weight 18-22 g, purchased from Shanghai Lingchang Biological Co., Ltd.).
- mice were starved for 12 hours, free to drink water, and were randomly divided into 5 groups according to body weight and starvation blood sugar.
- the mice were intragastrically administered, and 15 g after administration, 3 g/kg of starch was administered by gavage, and blood glucose was measured before, after, 30, 30, 60, 90, and 2 h of starch, and the administration time, body weight, and blood glucose were recorded.
- the effect of a single intragastric administration of deoxynojirimycin on oral glucose tolerance (mmol/L) in normal C57BL/6J mice is shown in Table 5.
- test substance 1-deoxynojirimycin is intragastrically administered to the starch 15 minutes after a single administration, and the blood glucose of the mice after the administration of the starch at 15 min and 30 min can be decreased in a dose-dependent manner.
- the area under the curve also showed a dose-dependent change at each time point, with an onset dose of 10 mg/kg and a hypoglycemic rate of 25.94% (AUC 0-2 h).
- AUC 0-2 h hypoglycemic rate
- blood glucose levels decreased slightly at 15 or 30 minutes after the sugar was given, but the overall area under the curve did not show a significant effect.
- the test substance Phl+DNJ can reduce the blood glucose of the mice after gavage to the starch at 15 min and 30 min in a dose-dependent manner, and the area under the curve also shows a dose-dependent change at each time point.
- the onset dose was Phl+DNJ (100+0.3) mg/kg, and the hypoglycemic rate was 17.71% (AUC 0-2h) (see Table 6, Figure 11, Figure 12).
- Example 10 In vivo pharmacodynamic experiment of sweet tea extract (root derrinin content 29.4%)
- mice were hungry for 12 hours, free to drink water, and were randomly divided into 3 groups according to body weight and starvation blood glucose.
- the mice were intragastrically administered, and 15 g after administration, 3 g/kg of starch was intragastrically administered, and blood glucose was measured before, after, 30, 30, 60, 90, and 2 h of the starch, and the administration time, body weight, and blood glucose were recorded.
- the effect of single oral administration of sweet tea extract on oral glucose tolerance (mmol/L) in normal C57BL/6J mice is shown in Table 7.
- sweet tea extract is 300mg/kg, which is slightly better than the hypoglycemic effect of single dose of phlorizin 100mg/kg (Example 7), suggesting that other ingredients contained in the extract may overlap or synergize.
- the effect of dermatan hypoglycemic is 300mg/kg, which is slightly better than the hypoglycemic effect of single dose of phlorizin 100mg/kg (Example 7), suggesting that other ingredients contained in the extract may overlap or synergize.
- the effect of dermatan hypoglycemic is 300mg/kg
- Example 11 In vivo pharmacodynamics experiment of mulberry leaf extract (1-deoxynojirimycin content 10%)
- mice 16 C57BL/6J mice (8-10 weeks old, gender: male, body weight 18-22 g, purchased from Shanghai Lingchang Biological Co., Ltd.).
- mice were starved for 12 hours, free to drink water, and were randomly divided into 2 groups according to body weight and starvation blood glucose.
- the mice were intragastrically administered, and 15 g after administration, 3 g/kg of starch was intragastrically administered, and blood glucose was measured before, after, 30, 30, 60, 90 min and 2 h of starch administration, and the administration time, body weight and blood glucose were recorded.
- the effect of single gavage administration of mulberry leaf extract on oral glucose tolerance in normal C57 mice (mmol/L) is shown in Table 8.
- Example 12 Pharmacodynamic experiment of sweet tea extract (root saponin content 29.4%) and mulberry leaf extract (1-deoxynojirimycin content 10%)
- mice were starved for 12 hours, free to drink water, and were randomly divided into 4 groups according to body weight and starvation blood sugar.
- the mice were intragastrically administered, and 15 g after administration, 3 g/kg of starch was intragastrically administered, and blood glucose was measured before, after, 30, 30, 60, 90, and 2 hours of starch administration, and the administration time, body weight, and blood glucose were recorded.
- the effect of single oral gavage administration of sweet tea extract and mulberry leaf extract (abbreviated as sweet + mulberry) on oral glucose tolerance (mmol/L) in normal C57BL/6J mice is shown in Table 9.
- the sweet tea extract + mulberry leaf extract can reduce the blood glucose level and the area under the blood glucose curve at each time point in a dose-dependent manner;
- the sweet + mulberry effect dose was (300 + 3) mg/kg (see Table 9, Figure 17, Figure 18).
- the hypoglycemic effect of the group of sweet + mulberry is (300+3) mg/kg is significantly better than that of sweet tea extract 300mg/kg and mulberry leaf extract 3mg/kg, suggesting that the mulberry leaf extract is beneficial to sweet tea.
- the hypoglycemic effect of the extract In the range of 300-303 mg/kg of the existing sweet tea extract and mulberry leaf extract, the ratio of the prescriptions is maintained in the range of 100:1 to 10:1, or even lower, and the hypoglycemic effect can be achieved.
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Abstract
L'invention concerne une composition d'un principe actif naturel destinée à faire baisser la glycémie. Ladite composition comprend un premier composant et un second composant. Le premier composant est sélectionné parmi la phlorizine, des extraits végétaux contenant de la phlorizine, ou des matières végétales brutes ou matières végétales traitées contenant de la phlorizine. Le second composant est sélectionné parmi la 1-désoxynojirimycine, des extraits végétaux contenant de la 1-désoxynojirimycine, ou des matières végétales brutes ou matières végétales traitées contenant de la 1-désoxynojirimycine. La composition peut permettre de diminuer efficacement le dosage d'administration de chaque ingrédient, et peut réduire le coût, tout en diminuant les effets indésirables qui peuvent survenir en prenant chaque ingrédient séparément.
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