WO2012071706A1

WO2012071706A1 - Pharmaceutical composition for preventing and treating diabetes and its complications

Info

Publication number: WO2012071706A1
Application number: PCT/CN2010/079277
Authority: WO
Inventors: 赵家振; 陈钰; 冯小平
Original assignee: 上海羿康生物科技有限公司
Priority date: 2010-11-30
Filing date: 2010-11-30
Publication date: 2012-06-07

Abstract

A pharmaceutical composition for preventing and treating diabetes and its complications, which comprises Ophiopogonis polysaccharide extract and chromium as effective components, as well as excipients. The Ophiopogonis polysaccharide extract is a water extract or water-alcohol extract. The chromium is chromic salt, preferably chromium picolinate. The ratio between Ophiopogonis polysaccharide extract and chromium is 50,000:1-1000. The pharmaceutical composition has effects of decreasing insulin resistance and significantly reducing blood sugar, in particular, can reduce the level of blood lipid and serum total cholesterol, reduce and improve diabetes complications.

Description

Pharmaceutical composition for preventing and treating diabetes and its complications

Technical field

The present invention relates to the field of medicine, and more particularly to a pharmaceutical composition for treating and preventing diabetes and its complications.

Background technique

Diabetes is a common chronic metabolic disease. With the continuous improvement of people's living standards, the number of patients with diabetes is increasing. There are more than 92 million people with diabetes in China, and another 100 million people will become patients. As a comprehensive disease with multiple causes, diabetes is difficult to cure, patients need long-term medication, and complications of diabetes often lead to serious consequences. Diabetes is clinically characterized by hyperglycemia. In typical cases, polyuria, polydipsia, polyphagia, and phlegm can occur, that is, symptoms of "three more and one less". In addition to acute symptoms such as ketotoxicity, hypoglycemia and coma, chronic complications include vascular disease and neuropathy. Vascular lesions mainly include podiatry, eye disease, heart disease and kidney disease. The study found that vascular lesions are mainly vascular atherosclerotic lesions of the corresponding organs. The direct cause of atherosclerosis is hyperlipidemia.

At present, according to different types of diabetes, diabetic patients usually use insulin and oral hypoglycemic agents. The hypoglycemic agents mainly include biguanides and sulfonylureas. These drugs are prone to drug resistance over a long period of time. Over time, the curative effect is less and less obvious and the contraindications are large when taken. For example, biguanides have been shown to cause lactic acidosis, especially in diabetic patients with renal insufficiency, with a mortality rate of up to 50%. However, hydrazide drugs often cause hypoglycemia in patients.

Plant polysaccharides have great potential in the field of anti-diabetes and have attracted widespread attention in the medical community. A method of treating diabetes in ginseng polysaccharides and astragalus polysaccharides is disclosed in Canadian Patent Application Serial No. CA20052520757.

Diabetes belongs to the category of "thirst quenching" in traditional Chinese medicine. Ophiopogon japonicus has the function of nourishing yin and fluid, and moistening the lungs and clearing the heart. It is used for the treatment of dryness and dryness of the lungs, thirst for the wounds, internal heat and thirst, etc. It is of great significance for improving immunity and preventing and treating diabetes. The Chinese patent application No. 200810043279.6 discloses the use of the Ophiopogon polysaccharide drug in the preparation of a medicament for diabetes. According to the report, is the β-D-fructan with a molecular weight of 5000 isolated from the extract of Ophiopogon japonicus? The symptoms of polydipsia, polydipsia and polyuria in rats with high blood sugar Has a certain blood sugar lowering effect.

In addition, vitamins and some sputum elements are known to have a positive effect on the treatment of diabetes and the improvement of symptoms of diabetes.

Chromium: Insulin is the only hormone in the body that has hypoglycemic properties. Active chromium can help or enhance insulin function. If the active chromium in the body is insufficient, the biological performance of insulin is lowered. Studies have shown that the chromium content in diabetic patients will decrease, and the presence or absence of complications in diabetic patients and the length of the disease are also related to chromium. The course of disease was longer and the serum chromium content decreased significantly; the chromium content with complications was significantly lower than that of patients without complications. If a diabetic has a serum chromium value of less than 15 nmol/l, the incidence of kidney disease and retinopathy is 71% and 77%, respectively.

People with diabetes can cause electrolyte metabolism disorders in the body due to disorders of glucose metabolism, which increases the amount of chromium excreted. People with diabetes also have a problem of reduced ability to convert chromium into active chromium and poor utilization of chromium. Therefore, normal dietary chromium can not meet the needs of diabetics, and additional chromium is needed.

It is reported in foreign countries that about 70% of diabetics have improved their condition after chrome supplementation, and can reduce insulin or oral hypoglycemic agents. It can also improve blood lipids and blood cholesterol levels, including lowering blood triglycerides, total cholesterol and increasing high density. The level of lipoproteins.

Experts from China and the United States performed a four-month chromium supplementation on 180 diabetic patients. The results showed that blood glucose, insulin, cholesterol and glycosylated hemoglobin were significantly improved. This report was published in the 1997 issue of Diabetes. In the magazine. In 1999, Chinese experts in the clinical observation of 833 diabetic patients for 10 months of chromium supplementation showed that only one month later, 90% of patients had improved fasting blood glucose and postprandial blood glucose, and remained at a low level for 10 months. In the state, more than 85% of patients after chrome supplementation improved clinical symptoms such as frequent urination, thirst and fatigue, and no side effects were observed. In 1999, experts in Tianjin added chromium to people with diabetes for four weeks. It was found that the patient's blood glucose decreased significantly after 2 hours of meal, and the effective rate was 60%-73.3%, indicating that chromium does have a role in assisting P. It can be seen that chromium has diabetes prevention. Significance.

Trace element chromium has a variety of valence states, the common ones are trivalent and hexavalent, and the valence states are different in nature. 6 valent chromium is toxic to the body and must not be eaten. What is good for our body is trivalent chromium. Studies have shown that it is absolutely safe to take 1000 micrograms of trivalent chromium per day.

Vitamins: Vitamin A has an antioxidant effect, which can have an important effect on lymphocyte activation, proliferation, differentiation and apoptosis. If vitamin A deficiency, it may cause autoimmune abnormalities, promote islet cell apoptosis, and aggravate diabetes, especially It has a great impact on type 1 diabetes. Fat-soluble vitamins and vitamin C have anti-oxidation, eliminate oxygen free radicals and lipid peroxides, and can be enhanced The body's immune function, vitamin C can also promote cholesterol metabolism. Vitamin D inhibits the autoimmune response of islet cells and reduces insulin resistance. If vitamin D deficiency can reduce insulin secretion, it becomes one of the predisposing factors of diabetes. Vitamin E can scavenge free radicals and reduce vascular endothelial damage. If vitamin E is chronically deficient and plasma levels are low, it can cause disorders of glucose metabolism and increase cardiovascular disease in diabetes. B vitamins are closely related to the function of coenzyme. When it is lacking, it can cause disorder of glucose metabolism, and it is a serious condition.

However, the cause of diabetes is complicated, and a single polysaccharide does not solve a series of symptoms and serious complications of diabetes. Similarly, the same problem exists with the single use of vitamins or trace elements. In particular, there is currently a lack of research in this field on the synergistic effect of plant polysaccharides with other active ingredients. Summary of the invention

In view of the above, an object of the present invention is to provide a safe, non-toxic and side-effect pharmaceutical composition which improves blood sugar metabolism, lowers blood sugar and blood lipids, improves blood circulation, and alleviates diabetes complications.

The inventors have found through in-depth study that the combination of Ophiopogon japonicus polysaccharide and elemental chromium has obvious synergistic effects in improving blood glucose metabolism, P-lowering blood sugar and blood lipids, improving blood circulation and alleviating diabetic complications. And thus completed the present invention.

Namely, the present invention provides a pharmaceutical composition for preventing and treating diabetes and its complications, which comprises as an active ingredient an extract of Ophiopogon japonicus polysaccharide, elemental chromium and an excipient.

In the present invention, the Ophiopogon japonicus polysaccharide extract is an aqueous extract of Ophiopogon japonicus or an aqueous alcohol extract. In the present invention, the chromium is usually a chromium salt, preferably chromium picolinate.

In the pharmaceutical composition, the ratio of the polysaccharide extract of Ophiopogon japonicus to chromium is 50,000:1 to 1000.

Preferably, the ratio of the extract of Ophiopogon japonicus polysaccharide to chromium is 15,000: 1 - 100, and more preferably the ratio of the extract of Ophiopogon japonicus polysaccharide to chromium is 5,000: 1 - 10.

In the present invention, it is preferred that the extract of Ophiopogon japonicus is a product obtained by pulverizing the roots of Ophiopogon japonicus, extracting with water, and ultra-filtering alcohol.

Preferably, the water extraction is carried out below 70 °C.

Preferably, the aqueous extract is subjected to ultrafiltration concentration by ultrafiltration membranes having a molecular weight of 10,000 daltons or less.

In the present invention, vitamins or trace elements or other effective ingredients may also be added to the pharmaceutical composition. Minute.

The present invention also provides the use of the combination of Ophiopogon japonicus polysaccharide and chromium in the preparation of a medicament for reducing blood glucose and glycated hemoglobin in a diabetic patient.

Further, the present invention provides the use of the combination of Ophiopogon japonicus polysaccharide and chromium in the preparation of a medicament for improving drinking water and diet of a diabetic patient.

Animal experiments have shown that the pharmaceutical composition of the present invention can improve the symptoms of polyphagia, polydipsia and polyuria in diabetic rats, and has certain hypoglycemic and hypolipidemic effects. Further, the pharmaceutical composition group of the present invention has a better hypoglycemic and blood lipid-lowering effect than the case of using the Ophiopogon japonicus polysaccharide extract alone or chromium pyridinium citrate alone. Therefore, the pharmaceutical composition of the present invention has remarkable effects of lowering blood sugar, lowering insulin resistance and lowering blood fat, and at the same time, can improve and reduce diabetic complications by improving patient immunity and the like.

BEST MODE FOR CARRYING OUT THE INVENTION The pharmaceutical composition for preventing and treating diabetes and its complications of the present invention is composed of an aspartame polysaccharide extract, elemental chromium and an excipient as a basic effective ingredient.

In the present invention, the Ophiopogon japonicus polysaccharide extract is an aqueous extract of Ophiopogon japonicus or an aqueous alcohol extract. In a preferred embodiment, the extract of Ophiopogon japonicus is a product obtained by pulverizing the roots of Ophiopogon japonicus, extracting with water, and then super-alcoholizing.

Preferably, the Ophiopogon japonicus polysaccharide extract is obtained by extracting the extract with ultra-filtration membrane having a molecular weight of 10,000 Dalton or less and then filtering it with an alcohol precipitate by extracting with water at a low temperature.

In the present invention, the Ophiopogon japonicus polysaccharide may be extracted with hot water or cold water, but is preferably extracted with cold water, that is, at a low temperature.

The low temperature means that the temperature is from room temperature to 70 ° C or less, preferably from 35 to 65 ° C, more preferably from 45 to 60 ° C.

In the present invention, the water as the extraction solvent may contain a small amount of ethanol, and it is preferred that the ethanol content is 20% or less, more preferably 10% or less.

In the present invention, the time for extracting the Ophiopogon polysaccharide from 7 is usually between 2 and 48 hours. In general, the extraction time is inversely proportional to the temperature of the solvent used. When the extraction temperature is high, the extraction time is short. Preferably, it is extracted with water at 35 - 65 ° C for 2 - 8 hours, preferably with water at 45 - 60 ° C for 2-4 hours. In the present invention, the extraction is usually carried out a plurality of times. The number of extractions is large, which is beneficial for the full extraction of polysaccharides from Ophiopogon japonicus. However, after a certain number of extractions, the polysaccharides that can be extracted are limited, and the cost is increased. Therefore, it is preferred that the extraction step be performed 2 _ 4 times, preferably 2 _ 3 times. After extraction, the extracts were combined for further processing.

In the present invention, the extract of Ophiopogon japonicus obtained by water extraction is appropriately concentrated, and then separated and further concentrated by ultrafiltration.

In the present invention, the type of the ultrafiltration membrane to be used is not particularly limited, and the material of the ultrafiltration membrane may be, for example, cellulose and its derivatives, polycarbonate, polyvinyl chloride, polyvinylidene fluoride, polysulfone, polyethersulfone. , polyacrylonitrile, polyamide, polysulfonamide, sulfonated polysulfone, crosslinked polyvinyl alcohol, modified acrylic polymer, etc., but preferably made of acetate fiber or a polymer material similar to its properties and polyacid sulfone.

In the present invention, the ultrafiltration membrane used has a cutoff molecular weight of 40,000 daltons or less, preferably 25,000 daltons or less, more preferably 10,000 daltons or less. This is because the hypoglycemic effect of the concentrated extract of Ophiopogon japonicus polysaccharides by filtration through an ultrafiltration membrane with a molecular weight cut below 10,000 Daltons is more pronounced.

In the present invention, the ultrafiltration membrane meeting the above requirements is, for example, Biomax-PB 10000 manufactured by Millipore Corporation of the United States having a molecular weight of less than 10,000 Daltons.

When filtering and concentrating with an ultrafiltration membrane, it is preferred to use an ultrafiltration membrane in combination with a high pressure difference extractor. In the present invention, for example, ultrafiltration concentration can be carried out by using Pellicon® XL of Biomax-PB.

In the present invention, the extract of Ophiopogon japonicus polysaccharide obtained by concentration after ultrafiltration is precipitated and separated by adding ethanol.

When the precipitate is separated by ethanol, the amount of the ethanol to be added is usually 1 - 3 times, preferably 1 - 2 times the volume of the concentrated polysaccharide of the polysaccharide obtained by concentration by ultrafiltration.

In the present invention, ethanol is added to the extract of the polysaccharide of Ophiopogon japonicus to precipitate, and then left at room temperature below room temperature overnight. It is preferably placed at 0 ° C or less overnight, more preferably at _ 10 ° C or less overnight.

In the present invention, the extract of Ophiopogon japonicus polysaccharide which is left overnight after the alcoholysis is separated by centrifugation, the precipitate is filtered, and freeze-dried to obtain the extract of Ophiopogon japonicus of the present invention.

The polysaccharide content of the polysaccharide extract of Ophiopogon japonicus was determined by the 3,5-dinitrosalicylic acid (DNS) colorimetric method.

In the present invention, in the extract of Ophiopogon japonicus obtained by the above method, in addition to the polysaccharide, there are also ophiopogonin such as Ophiopogon saponins A, B, B', C C', D, D', High flavone Compounds such as flavonoids A, B, lysine flavonoids A, B, dihydro-glycoside A, B, methyl dihydro-glycoside, 6-acid isoflavone and 6-case Alkaloids A, B. In addition, it also contains volatile oils, phytosterols, monosaccharides and oligosaccharides.

In the present invention, in addition to the extraction of the Ophiopogon polysaccharide by the aforementioned method. It is also possible to use products currently available on the market, such as the polysaccharide extract ZL-SE015 produced by Guangzhou Zeli Pharmaceutical Technology Co., Ltd. (it is a white powder extracted by low temperature and high pressure difference).

In the pharmaceutical composition of the present invention, the chromium is trivalent, which is most stable in biological systems. In the present invention, the chromium is in the form of a chromium salt, preferably chromium picolinate.

In the present invention, the ratio of the extract of Ophiopogon japonicus polysaccharide to chromium is 50,000:1 to 1000, preferably 15,000:1 - 100, more preferably 5,000:1 - 10 in the pharmaceutical composition.

In the pharmaceutical composition of the present invention, a combination of an extract of Ophiopogon japonicus polysaccharide and chromium is used as an active ingredient. However, in addition to the above two active ingredients, other active ingredients for the treatment and prevention of diabetes may be added, for example (eg, sulfonylurea glipizide, gliclazide, glibenclamide, glibenclamide, Glimepiride, etc., biguanides (such as diterpene, etc.), alpha glycosidase inhibitors (such as acarbose, voglibose, etc.), insulin sensitizers (such as rosiglitazone, Regal) Linnai, etc., can also be added to Chinese herbal extracts such as Dihuang, Mulberry, Ginseng, Zhimu, and Coptis.

In the pharmaceutical composition of the present invention, a small amount of vitamins and other microelements other than chromium may also be added.

The vitamin is one or more of vitamin Α, multivitamin Β, vitamin C, vitamin D, and vitamin E.

The trace element is one or more of zinc, selenium, copper, manganese, iron, and molybdenum.

The present invention also provides a method for preparing an Ophiopogon japonicus polysaccharide, which comprises pulverizing the Ophiopogon japonicus root, extracting with water, and obtaining an Ophiopogon japonicus polysaccharide by ultrafiltration and alcohol precipitation.

The present invention also provides a method of preparing a pharmaceutical composition for preventing and treating diabetes and its complications, which comprises administering a prescribed amount of the polysaccharide extract of Ophiopogon japonicus, chromium and optional vitamins, trace elements or other materials as excipients. The active ingredient and excipients are mixed to prepare the desired dosage form.

In the present invention, the excipient refers to an additional material other than the main drug which can increase the stability, pH value, permeability, bioavailability and transparency of the preparation of the present invention without causing side effects and without affecting the therapeutic effect. , including but not limited to binders, fillers, disintegrants, lubricants, preservatives, antioxidants, flavoring agents, fragrances, solubilizers, emulsifiers, solubilizers, osmotic pressure regulators, colorants, etc. . The pharmaceutical composition of the present invention can be formulated into various pharmaceutical dosage forms suitable for oral administration, intravenous administration, sublingual administration, and the like. It is used in the form of a solid, a solution, an emulsion, a dispersion, a micelle, a liposome, etc., and the specific use forms include tablets, granules, pills, capsules, tablets, suspensions or suspensions, elixirs, Dispersible powders, solutions, emulsions, suspensions and other suitable forms. Useful carriers include lactose, dextrin, microcrystalline cellulose, gum arabic, gelatin, mannitol, starch paste, magnesium stearate, talc, silica gel, and others suitable for production in solid, semi-solid or liquid form. Carrier. In addition, auxiliary agents, stabilizers, thickeners, and one or more flavoring agents, coloring agents, preservatives, and the like may be used to provide a palatable pharmaceutical product. Preferably, microcrystalline cellulose, dextrin, lactose, magnesium stearate are selected as pharmaceutical excipients.

The pharmaceutical composition of the present invention formulated into a suitable dosage form comprises a therapeutically effective amount of Ophiopogon japonicus polysaccharide extract and chromium and a ratio of 50,000:1 to 1000, preferably 15,000:1 to 100, more preferably 5,000:1 to 10 Shape agent.

The dosage of the pharmaceutical composition of the present invention depends on the symptoms, the course of the disease and the body weight of the patient, and usually can be administered daily to the polysaccharide of wheat, 1 - 200 mg / kg body weight, chromium 0.1 - 2 (^ g / kg body weight, preferably The daily administration of Ophiopogon japonicus polysaccharides is 5-40 mg/kg body weight, chromium 0.5-15 g/kg body weight. 2 to 3 times per day, 4 to 8 hours apart. Further, the present invention is further combined with the examples. The following examples are merely illustrative of the invention and are not to be considered as limiting the scope of the invention.

Take the Liliaceae plant Ophiopogon japonicus (Thunb.) Ker-Gawl.) 10 kg of dried roots, crush, add 120 L of water, and extract at 60 ° C for 2 hours. The extract was concentrated by ultrafiltration using Biomax-PB 10000 (product of Millipore). After adding 80 L of water to the residue, the mixture was extracted at 60 ° C for 2 hours, and then concentrated by ultrafiltration in the same manner. Further, 50 L of water was added to the residue, and after extracting at 60 ° C for 2 hours, the ultrafiltration was concentrated in the same manner. The filtrates were combined and concentrated under reduced pressure to ca. 18L. 18 L of 95% ethanol was added to the concentrate, and the mixture was allowed to stand at -15 ° C overnight, and the precipitate was removed by centrifugation, followed by lyophilization to obtain 470 g of an extract of Ophiopogon japonicus. The polysaccharide content of the extract of Ophiopogon japonicus polysaccharide was determined to be about 85% by 3,5-dinitrosalicylic acid (DNS) colorimetric method. Example 2:

200 g of the Ophiopogon japonicus polysaccharide extract of Example 1 and 66.7 mg of chromium pyridinium citrate were added to 80 mL of water to dissolve them uniformly, and then the extract thick paste was added to 790 g of microcrystalline cellulose and stirred well. Further, sodium carboxymethylcellulose lO.Og was prepared, and a 10% solution was prepared, added to the above microcrystalline cellulose mixture, mixed, sieved through a 40 mesh sieve, dried at 60 ° C, and sieved through a 40 mesh sieve. Granules containing Ophiopogon japonicus polysaccharide and chromium picolinate are obtained. Example 3

The pellets obtained were compressed in 400 g. Tablets weighing 5% by weight 5% of the tablets Example 4

The tablet (140 g) obtained in Example 3 was placed in a coating machine using hydroxypropyl decyl cellulose (149.2 g), titanium dioxide (20 g), polyethylene glycol 6000 (30 g), ferric oxide. A coating suspension of (0.8 g) and water (2000 g) was coated to obtain a film-coated tablet.

Example 5

The granules obtained in Example 2 were ground, and 300 mg was placed in a gelatin capsule to obtain a capsule preparation.

Example 6

Experimental study on hypoglycemic effect of pharmaceutical composition

Experimental animals 60 clean grade Wistar rats weighing (230 ± 20) g. Rats were housed in cages, placed at temperature (20 ± 2) °C, humidity 55% ~ 65%, light 121! ~ 24h, free drinking water environment.

Feed Standard standard feed: flour 20%, rice flour 10%, corn 20%, bran 25%, bean 20%, bone meal 2%, fish meal 2%

High-fat and high-sugar feed: 10% lard, 20% sucrose, 10% egg yolk powder, 0.5% sodium cholate and 59.5% of the above standard feed.

Rat model of diabetes was randomly divided into groups. Ten of them were used as normal control group (blank group), fed with normal standard feed, and the other 50 were given high-sugar and high-fat diet. After 5 weeks, high-fat and high-sugar diet was given. The animals were fed with an intraperitoneal injection of 0.75 mL of 1% streptozotocin (purchased from Sigma). After 72 hours, fasting blood glucose >16.7 mmol/L or more was used as a model for successful diabetes mellitus. 43 successful. Ten rats in the control group were fed with normal diet for 5 weeks, and an equal volume (0.75 mL) of 1% citrate buffer was intraperitoneally injected.

Forty-three diabetic rats (DM rats) were randomly divided into 4 groups: model group (N = 10), Ophiopogon japonicus polysaccharide + chromium pyridinium citrate (Example 1 of Ophiopogon japonicus polysaccharide extract 30 mg) + Chromium picolinate 100 g/kg) Treatment group (N = 11), Ophiopogon japonicus polysaccharide (Extraction 30 mg/kg of Example 1) Treatment group (N = 11), Chromium picolinate (10 C ^ g / kg) treatment Group (=11). Each group was intragastrically administered with the above-mentioned drug dose. The normal control group was given 1 mL/lOOg of normal saline per day. The DM rats were fed with high-fat and high-sugar diet, and the blank group was fed with normal feed for 9 weeks. Experimental indicators and measurement methods:

Blood glucose measurement, after 8 hours of fasting, was measured by a blood glucose meter using a tail-measuring method.

Determination of blood lipids, blood was collected in the fasting morning, and triglyceride and cholesterol were determined by enzyme colorimetry.

The diet, drinking water, and urine volume were measured. The metabolic cage was used to measure the rats' diet, drinking water, and collecting 24 h urine at 3 weeks, 6 weeks, and 9 weeks, respectively, and the changes were observed.

The body weight was measured, and the body weight of the rats was weighed at the 3rd week, the 6th week, and the 9th week, and the changes were observed.

See the table below for the results. Table 1 Changes in diet of each group after modeling (unit: g/24 hours)

The above table shows that at the 3rd week, the 6th week, and the 9th week after administration, the diet of each rat model group was significantly increased compared with the normal control group; however, compared with the model group, the polysaccharide of Ophiopogon japonicus + The chromium group diet was significantly reduced at 6 and 9 weeks after administration, and the diet of the Ophiopogon japonicus polysaccharide group and the chromium pyridinium citrate group was administered. 9 weeks also decreased. Changes in drinking water of each group after modeling (unit: ml/24 '

The above table shows that at the 3rd week, the 6th week, and the 9th week after treatment, the drinking water in the rat model group was significantly increased compared with the normal control group; however, compared with the model group, the rats in the three treatment groups were compared. Drinking water is significantly reduced. Changes in urine volume of each group after modeling (unit: ml/24 hours)

The above table shows the changes in urine volume during the treatment of each group of rats: At the 3rd week, the 6th week, and the 9th week after the treatment, the urine volume of each rat model group was significantly increased as compared with the normal control group. Compared with the urine volume of the model group, the polysaccharides from the Ophiopogon japonicus + chromium group decreased significantly, while the urine volume of the Ophiopogon japonicus polysaccharide group and the chromium picolinate group decreased slightly. Table 4 The weight of each group after different models in different time periods ( g )

White group model group, Ophiopogon japonicus, Polypyridinium citrate, Chromium group, Chromium group 3 387 士20 310士19 321 ±23 313士22 309士17 weeks later

6 448士 31 311士 17 337士 19 309士 14 319士 22 weeks later

9 470 士 29 314 士 20 351 士 17 320 士 10 308 士 12 weeks later

The above table shows that there was a significant decrease in body weight of each rat model group during the entire administration period as compared with the blank control group. Compared with the model group, the body weight of the Ophiopogon japonicus polysaccharide + chromium group increased significantly, but the body weight of the Ophiopogon japonicus polysaccharide group and the Pyridinium S cross chromium group were not significant. Changes in blood glucose and glycated hemoglobin in each group at the end of the experiment (unit: mmol/L)

The above table shows that compared with the normal control group, blood glucose and glycated hemoglobin were significantly increased in each rat model group; compared with the model group, the blood glucose and glycated hemoglobin of the Ophiopogon japonica polysaccharide + chromium group were significantly decreased, while the Ophiopogon japonicus polysaccharide group and pyridine In the 铬g history chromium group, blood glucose was significantly reduced, but there was no significant change in hemoglobin. Changes in blood lipids in each group at the end of the experiment (unit: mmol/L)

Blank group model group Ophiopogon japonicus polysaccharide Ophiopogon japonicus polysaccharide picolinic acid

+chromium group chromium group

Total 0.9 0.33 2.47士 1.02 1.34士 0.15 2.01士 1.13 1.99士 1.37 Cholesterol

Gan 0.54±0.21 1.63±0.57 0.67±1.42 1 ·21±0·93 1.15±2.14 oil triester Height 0.47±0.14 0.64±0.11 0.60±1.31 0.62±2.10 0.59±0.34 Density grease

Protein

The study found that the pathological causes of diabetic complications of foot disease, heart disease and eye disease are mainly vascular atherosclerotic lesions of the corresponding organs. The direct cause of arteriosclerosis is the amount of blood lipids.

The above table shows that compared with the normal control group, the blood lipids of each rat model group increased significantly; compared with the model control group, the blood lipids of the wheat winter polysaccharide treatment group were significantly reduced, while the Ophiopogon japonicus polysaccharide group and the pyridine group

5 δ history chromium group decreased blood lipids, but not obvious. From the above five observations, it can be seen that after 9 weeks of administration of the Ophiopogon japonicus polysaccharide + chromium compound, the diet, drinking water, urine volume and body weight of the group of rats were significantly reduced. Moreover, at the end of the experiment, the blood glucose, glycated hemoglobin and blood lipids of this group were significantly reduced compared with the model group. It is indicated that the pharmaceutical composition consisting of Ophiopogon japonicus polysaccharide and O-chromium of the present invention has a significant hypoglycemic and blood lipid-lowering effect. Simultaneous comparison of equal amount of polysaccharides

In the treatment group and the chromium pyridinium phosphate treatment group, it can be found that the combination of Ophiopogon japonicus polysaccharide and chromium has much better therapeutic effect on hyperglycemia and blood lipid than when they are used alone. From this, it is explained that the pharmaceutical composition of the present invention has a synergistic effect between the polysaccharide of the Ophiopogon japonicus and the chromium, and has an unexpected gain effect after the combination. According to the present invention, the pharmaceutical composition prepared by the combination of Ophiopogon japonicus polysaccharide and chromium has a significant hypoglycemic and hypolipidemic effect, and has significant effects on diabetic and diabetic vascular lesions.

The therapeutic effect. The above description by way of examples is only to help understand how the invention is implemented. It should be noted that those skilled in the art can make modifications and improvements to the present invention without departing from the spirit and scope of the present invention. These modifications and improvements are also considered to be required by the present invention.

Within the scope of protection.

Claims

Rights request

A pharmaceutical composition for preventing and treating diabetes and its complications, comprising as an active ingredient an extract of Ophiopogon japonicus polysaccharide, elemental chromium and an excipient.

The pharmaceutical composition according to claim 1, wherein the extract of Ophiopogon japonicus is an aqueous extract of Ophiopogon japonicus or an aqueous alcohol extract.

The pharmaceutical composition according to claim 1, wherein the chromium is chromium pyridinium citrate.

The pharmaceutical composition according to claim 1, wherein the ratio of the extract of Ophiopogon japonicus polysaccharide to chromium is 50,000:1 to 1000.

The pharmaceutical composition according to claim 4, wherein the ratio of the polysaccharide of Ophiopogon japonicus to chromium is 15,000:1 to 100.

The pharmaceutical composition according to claim 5, wherein the ratio of the polysaccharide of the Ophiopogon japonicus to chromium is 5,000:1 to 10.

The pharmaceutical composition according to claim 2, wherein the extract of Ophiopogon japonicus is a product obtained by pulverizing the roots of Ophiopogon japonicus, extracting with water, and then super-filtering alcohol.

The pharmaceutical composition according to claim 7, wherein the water extraction is carried out at 70 ° C or lower.

The pharmaceutical composition according to claim 7, wherein the aqueous extract is subjected to ultrafiltration concentration by an ultrafiltration membrane having a molecular weight of less than 10,000 Daltons.

The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition further comprises vitamins and/or trace elements.

11. The use of combination of Ophiopogon japonicus polysaccharide and chromium in the preparation of a medicament for reducing blood glucose and glycated hemoglobin in diabetic patients.

12. Use of a combination of Ophiopogon japonicus polysaccharide and chromium in the preparation of a medicament for improving drinking water and diet in diabetic patients.