HK1071688A - Nutritional composition for controlling blood sugar level - Google Patents

Description

Nutritional composition for controlling blood glucose levels

Technical Field

The nutritional composition is used for patients with diabetes or abnormal glucose intolerance, or is used for preventing and treating obesity.

Background field of the invention

In recent years, the number of diabetic patients has increased with westernization of dietary habits. Including the numerical estimates of potential patients, reach 1500 million. In the treatment of diabetes, dietary therapy and exercise are essential. The purpose of these treatments is mainly to normalize the metabolic disorders of the patient to the maximum, to correct insulin hyposecretion or insulin resistance, which is a factor causing diabetes, or to prevent or inhibit the development of vascular complications. Obesity is considered to be the leading cause of sixty to eighty percent of cases of diabetes. Since excessive insulin secretion is common to most obese patients, it is likely that when obesity exceeds a certain level, the insulin secretion becomes too high, leading to worsening of obesity [ diet 21 (Food Style 21), p.46, 2002.5 (Vol.6, No. 5) ].

In the united states, with advances in clinical nutrition science, a variety of oral or tube-fed (enteral) nutritional supplements have been developed for different disease states from the second half of the 80 s to the early 90 s of the 20 th century. Examples include "Glucerna" for diabetic patients, "superena" for renal disease patients who have not received artificial dialysis, "Nepro" for renal disease patients who need artificial dialysis, "active" for all patients in invasive stage, especially those with impaired digestive tract, "AlitraQ" for patients in invasive stage, and "Advera" for AIDS patients. In recent years, "OXEPA" for patients with Acute Respiratory Distress Syndrome (ARDS) has been marketed. These products account for more than 70% of the nutritional supplements for oral or tube feeding in the united states for pathological conditions [ diet 21, page 54, 1991.1 (volume 3, No. 1) ]. On the other hand, in japan, "YH-80" is a thick liquid food developed for patients with severe burns, "fibrone YH" has a composition closer TO the standard diet than YH-80, "Renalene" is used for patients with impaired renal function, "Meibalance C" is a full nutritional liquid food designed for the elderly [ diet 21, page 58, 1991.1 (volume 3, No. 1) ], and high nutritional liquid food a-3 is used for unconscious patients [ ISO TO rinshi 29 (17): 4529-4543, 1995], all of which have been put on the market. However, liquid foods such as "Glucerna" for diabetic patients have not yet been put on the market.

Some patents and patent applications relate to the presence of liquid foods, but the number of those related to diabetes is still small. It has hitherto been exclusively recognized that a nutritional composition for diabetic patients contains a predetermined energy percentage of proteins, lipids and carbohydrates, which are added together with viscous soluble dietary fibers and inulin or a hydrolysate thereof (Japanese patent laid-open publication No. Hei 11-18725).

It is therefore an object of the present invention to provide a nutritional composition effective for the nutritional regulation and control of blood glucose levels in patients with abnormal glucose metabolism or for the prevention of obesity. More specifically, the object of the invention is to provide a nutritional composition for diabetic patients or persons suffering from abnormal glucose intolerance or for preventing obesity, which composition is effective in suppressing a sharp rise in postprandial blood glucose levels caused by low insulin secretion and insulin resistance and in increasing the level of glycaemic pigment (HbAlc), which reflects blood glucose levels over a long period of time.

Disclosure of Invention

Isomaltulose (palatinose) is an iso-disaccharide in which glucose and fructose form an α -1, 6 linkage. Like sucrose, it is digested and absorbed as glucose and fructose [ Toshinao Aida et al: japan Journal of Nutrition and Food Science (Journal of Japanese Society of Nutrition and Food Science), 36(3) Vol.169-173, 1983 ]. Since isomaltulose hydrolyzes at a rate of one fifth of sucrose [ Tsuji y, et al: j. nutr. sci. vitaminol., 32, 93-100, 1986], blood glucose and insulin levels after isomaltulose ingestion can be maintained at predetermined levels after many hours [ Kawai, k. et al: endocrinol, Japan, 32(6), 933-936, 1985 ].

1-O-alpha-D-glucopyranosyl-beta-D-fructose (trehalulose) is an iso-disaccharide in which glucose and fructose form an alpha-1, 1 linkage. This material is a non-carious sweetener that aids in digestion and has a physiological resemblance to isomaltulose. Like isomaltulose, this material is digested in the small intestine by isomaltase and absorbed as glucose and fructose. The rate of hydrolysis of 1-O- α -D-glucopyranosyl- β -D-fructose in the small intestine is one third of that of sucrose and about twice that of isomaltulose [ Yamada k., Shinohara h. et al: international Nutrition report (Nutrition Reports International), 32(5), 1211-1219, 1985.

The Ministry of health and welfare (Ministry of health, labor, and welfare) recommends varying the recommended intake ratio of saturated fatty acids (SFA: palmitic acid, stearic acid, etc.), monovalent unsaturated fatty acids (MUFA: oleic acid, etc.), and polyvalent unsaturated fatty acids (PUFA: linoleic acid, linolenic acid, etc.) from 1: 1.5: 1 to 3: 4: 3, and adjusting the ratio of n-6 series fatty acids to n-3 series fatty acids to 4: 1. The above change was made because it was difficult to consume foods containing MUFA ratios of up to 1.5 in japan.

The present invention therefore prepares a nutritional composition containing a specific energy percentage of protein, lipid and carbohydrate content and studies its effect on fasting normal animal blood glucose levels. As a result, the nutritional composition shows an increase inhibition of blood glucose level similar to Glucerna, a commercial liquid food for diabetic patients. The effect of this nutritional composition on the inhibition of the rise in sugar level and the alleviation of morbidity was investigated with experimental diabetes model animals and spontaneous diabetes model animals, and as a result, the composition exhibited an inhibition of the increase in blood sugar level similar to Glucerna and at the same time exhibited a significant lipid metabolism-promoting effect relative to Glucerna. When a single oral administration experiment of this nutritional composition was conducted with normal health testers, insulin was kept at a low level after administration. In addition, its effect on visceral fat accumulation in normal animals was investigated, showing a visceral fat accumulation inhibition higher than Glucerna and Meibalance C. From the above results, it was found that this nutritional composition is effective in controlling blood glucose levels or preventing obesity in patients suffering from diabetes or glucose intolerance, leading to the completion of the present invention.

The present invention therefore provides a nutritional composition for controlling blood glucose levels comprising protein, lipid and carbohydrate, wherein the percentage of energy provided by the protein, lipid and carbohydrate is from 10 to 25%, from 20 to 35% and from 40 to 60%, respectively; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

The invention also provides the use of a composition comprising proteins, lipids and carbohydrates for the manufacture of a nutritional composition for the control of blood glucose levels and the prevention of obesity, wherein the percentage of energy provided by the proteins, lipids and carbohydrates is between 10 and 25%, between 20 and 35% and between 40 and 60%, respectively; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

The present invention further provides a method for controlling blood glucose levels and preventing obesity characterized by administering to a patient a nutritional composition for controlling blood glucose levels, the composition comprising proteins, lipids and carbohydrates wherein the percentage of energy provided by the proteins, lipids and carbohydrates is 10 to 25%, 20 to 35% and 40 to 60%, respectively; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

Brief Description of Drawings

Figure 1 shows the change in blood glucose levels following oral administration of each nutritional composition and Glucerna to normal rats. In the diagram, (- ● -) refers to the nutritional composition, (-. O. cndot.) refers to Glukerna. Each point is the mean ± standard deviation (n ═ 6). *: p is less than 0.05: significantly different from Glucerna (student's t test).

Figure 2 shows the change in blood glucose levels following a single oral administration of each nutritional composition and Meibalance C to normal rats. In the diagram, (- ● -) denotes the nutritional composition, (. tangle-solidup. cndot.) denotes the Meibalnce C. Each point is the mean ± standard deviation (n ═ 6). *: p is less than 0.05: significantly different from Meibalance C (student's t test).

Figure 3 shows the change in blood glucose levels following a single oral administration of each nutritional composition, Glucerna and Meibalance C to normal rats. In the diagram, (- ● -) denotes the nutritional composition, (. smallcircle. cndot. cndot. Each point is the mean ± standard deviation (n ═ 6). *: p is less than 0.05: significantly different from MeibalanceC (student's t test).

Figure 4 shows the change in blood glucose levels after oral administration of each nutritional composition and Meibalance C to streptozotocin-induced diabetic rats. In the diagram, (- ● -) denotes the nutritional composition, (. cndot. cndot.) denotes the Meibalance C. Each point is the mean ± standard deviation (n ═ 6). *: p is less than 0.05: significantly different from Meibalance C (student's t test).

Figure 5 shows the change in blood glucose levels after a single oral administration of each nutritional composition, Glucerna and Meibalance C to streptozotocin-induced diabetic rats. In the diagram, (- ● -) denotes the nutritional composition, (. cndot. cn. Each point is the mean ± standard deviation (n ═ 6). *: p is less than 0.05: significantly different from Meibalance C (student's t test).

Fig. 6 shows the change in blood glucose levels following a single oral administration to GK rats of one of the following: nutritional composition, Glucerna or Meibalance C. In the diagram, (- ● -) denotes the nutritional composition, (. cndot. cn. Each point is the mean ± standard deviation (n ═ 6). *: p is less than 0.05: significantly different from Meibalance C (student's t test).

FIG. 7 shows the weight change at 9 weeks after spontaneous diabetes model mice G57BL/Ksj-db/db jc1 were fed one of the following ad libitum: nutritional composition, Glucerna or Meibalance C powder. In the diagram, (- ● -) denotes the nutritional composition, (. cndot. cn. Each point is the mean ± standard deviation (n ═ 8).

Figure 8 shows the change in blood glucose levels 31 days after mice similar to the above species were ad libitum fed one of: nutritional composition, Glucerna or Meibalance C powder. In the graph, (■) refers to nutritional composition, (□) refers to Glucerna and (. diamond-solid.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 8). *: p is less than 0.05: there were no significant differences when the letters were identical (Mann-Whitney U-test).

FIG. 9 shows the change in HbAlc levels 31 days after mice similar to the above mouse species were ad libitum fed one of the following: nutritional composition, Glucerna or Meibalance C powder. In the graph, (■) refers to nutritional composition, (□) refers to Glucerna and (. diamond-solid.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 8). *: p is less than 0.05: there were no significant differences when the letters were identical (Mann-Whitney U-test).

Figure 10 shows serum GOT levels at 9 weeks after ad libitum feeding mice similar to the above mouse species with one of the following: nutritional composition, Glucerna or Meibalance C powder. In the graph, (■) refers to nutritional composition, (□) refers to Glucerna and (. diamond-solid.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 8). *: p is less than 0.05: there were no significant differences when the letters were identical (Mann-Whitney U-test).

Figure 11 shows serum GPT levels 9 weeks after ad libitum feeding mice similar to the mouse species described above with one of the following: nutritional composition, Glucerna or Meibalance C powder. In the graph, (■) refers to nutritional composition, (□) refers to Glucerna and (. diamond-solid.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 8). *: p is less than 0.05: there were no significant differences when the letters were identical (Mann-Whitney U-test).

Figure 12 shows the accumulated neutral fat in each liver at 9 weeks after ad libitum feeding mice similar to the mouse species described above with one of: nutritional composition, Glucerna or Meibalance C powder. In the graph, (■) refers to nutritional composition, (□) refers to Glucerna and (. diamond-solid.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 8). *: p is less than 0.05: there were no significant differences when the letters were identical (Mann-Whitney U-test).

Figure 13 shows the amount of neutral fat accumulated per gram of liver in 9 weeks after ad libitum feeding mice similar to the mouse species described above: nutritional composition, Glucerna or Meibalance C powder. In the graph, (■) refers to nutritional composition, (□) refers to Glucerna and (. diamond-solid.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 8). *: p is less than 0.05: there were no significant differences when the letters were identical (Mann-Whitney U-test).

FIG. 14 shows the energy intake changes 1 month after C57BL/6N Jc1 mice were fed ad libitum with each nutritional composition, Glucerna or MeibalanceC powder. In the graph, (●) refers to the nutritional composition, (. smallcircle) refers to Glucerna and (. DELTA.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 9). *: p is less than 0.05: Mann-WhitneyU-test.

Figure 15 shows the weight change 1 month after ad libitum feeding of mice similar to the above mouse species with one of the following: nutritional composition, Glucerna or Meibalance C powder. In the graph, (●) refers to the nutritional composition, (. smallcircle) refers to Glucerna and (. DELTA.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 9). *: p is less than 0.05: Mann-Whitney U-test.

Figure 16 shows the amount of retroperitoneal fat (% by weight) 9 weeks after ad libitum feeding mice similar to the above mouse species with one of the following: nutritional composition, Glucerna or Meibalance C powder. In the graph, (■) refers to nutritional composition, (□) refers to Glucerna and (. diamond-solid.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 9). P < 0.05: Mann-Whitney U-test.

Fig. 17 shows epididymal fat mass 1 month after mice similar to the above mouse species were fed one of the following ad libitum: nutritional composition, Glucerna or Meibalance C powder. In the graph, (■) refers to nutritional composition, (□) refers to Glucerna and (. diamond-solid.) refers to Meibalance C. Each point is the mean ± standard deviation (n ═ 9). P < 0.05: Mann-Whitney U-test.

Best mode for carrying out the invention

The nutritional compositions of the invention (hereinafter referred to as "nutritional compositions" or "compositions") contain from 10 to 25%, preferably from 10 to 20%, of protein by energy percentage in the composition.

Examples of the protein include milk protein, protein obtained from plants, and soybean protein or a hydrolysate thereof. Among them, milk protein is preferable. Examples of the milk proteins include MPC (milk protein concentrate), casein proteins, whey proteins, magnesium caseinate, their hydrolysates, fermented milk, and ingredients obtained by removing whey from fermented milk (fresh cheese, crude skim yogurt cheese, etc.) (japanese patent laid-open publication No. hei 5-252896). Of these MPC and MPC in combination with casein are preferred.

Examples of whey proteins include whey powder obtained by concentrating and drying whey, whey protein obtained by concentrating whey by Ultrafiltration (UF) and then drying, defatted WPC (low fat and high protein content) obtained by removing fat from whey and then UF concentrating, WPI obtained by selectively separating only protein from whey, desalted whey obtained by ultrafiltration (nanofiltraction) concentration, mineral-concentrated whey in which the mineral component from whey is concentrated.

The nutritional compositions of the invention contain 20 to 35% by energy of lipids, preferably 20 to 30% in the composition. This ratio is based on the Recommended Dietary allowance of Japan (the Recommended Dietary allowance for the Japanese), revision 6. To increase the content of Monovalent Unsaturated Fatty Acids (MUFA) in the lipid in the fatty acid composition, a monovalent unsaturated fatty acid, oleic acid, is incorporated into the lipid at an energy percentage of 60 to 90%, preferably 60 to 80%. Examples of lipid sources abundant in oleic acid include high oil sunflower oil, soybean oil, corn oil and palm oil, each with a high oleic acid content. The lipid source abundant in oleic acid is for example a nutritionally controlled oil or fat (NOF product). Sunflower oil, rapeseed oil, olive oil and mixtures with olive oil may also be used.

As another lipid, a phospholipid or lecithin derived from milk (obtained from soybean or egg yolk) is preferred.

Milk phospholipids are only present in milk fat globule membranes (FFGM). Examples of milk phospholipids containing high amounts of MFFM include lyophilisates of WPI by-products (MF retentate) prepared by Ultrafiltration (UF) combined with Microfiltration (MF) to obtain a fraction (cream whey) by removing milk fat from whey cream. The liquid fraction obtained by eluting cream whey several times with ethanol and then centrifuging or the fraction insoluble in acetone (alpha-lipids: Anchor Products/New Zenland product) can also be used.

Lecithin is chemically referred to as Phosphatidylcholine (PC), however it generally refers to a mixture of 4 compounds, namely PC, Phosphatidylethanolamine (PE), Phosphatidylinositol (PI) and phosphatidic acid (PE) and another phospholipid. In the present invention, these lecithins can be used. In addition, lecithin paste has acetone insoluble portion for indicating phospholipid purity from 62 to 65%, high purity powder lecithin has a phospholipid content of 95% or more, and fractionated lecithin phosphatidylcholine content is increased.

The composition of the present invention may comprise polyvalent unsaturated fatty acids of the n-6 series and polyvalent unsaturated fatty acids of the n-3 series. Preferably, these multivalent unsaturated fatty acids are present in an amount of 10 to 40% of the fatty acid composition, preferably 30%. For example, these multivalent unsaturated fatty acids may be incorporated into the fatty acid composition in an amount of about 20%.

With respect to the lipid composition of the nutritional composition, the n-6 series of multivalent unsaturated fatty acids and the n-3 series of multivalent unsaturated fatty acids may be combined in a ratio of about 5: 1 to about 1: 1, with about 4: 1 being preferred. For this purpose, it is recommended to combine perilla oil or linseed oil containing a high proportion of n-3 series alpha-linolenic acid. DHA-rich bonito or tuna oil can also be used.

In the present invention, at least one selected from milk lecithin, soybean lecithin, high-oil sunflower oil and perilla seed oil is preferably used as the lipid.

In the nutritional composition of the invention, the carbohydrates are combined with an energy percentage of 40 to 60%, preferably 50 to 60%. This energy percentage corresponds approximately to the recommended dietary grant of japan, revision 6. The carbohydrates isomaltulose, 1-O- α -D-glucopyranosyl- β -D-fructose or mixtures thereof are used. Isomaltulose, 1-O- α -D-glucopyranosyl- β -D-fructose or mixtures thereof are bound to the carbohydrate at an energy percentage of 60 to 100%, preferably 60 to 80%.

Additional examples of carbohydrates include sugar alcohols (sorbitol, xylitol and maltitol), trehalose, palatinit (trade name for isomalt), maltodextrin, processed starch, amylose, tapioca starch, fructose and lactose and mixtures thereof. Among them, maltodextrin, xylitol and a mixture thereof are preferable. Maltodextrin is a sugar, an intermediate obtained by acid hydrolysis or enzymatic hydrolysis of starch or corn starch and has a DE value of 20 or less.

The nutritional composition of the present invention may further comprise dietary fibre. The dietary fiber may be water soluble dietary fiber or water insoluble dietary fiber. Examples of water-soluble dietary fibers include lightly digestible dextrins, gums, glucomannans, alginic acid hydrolysates, guar resins, guar resin products obtained by enzymatic hydrolysis, and galactomannans. Slightly digestible dextrin is preferred because it can be easily added to food and does not disturb food processing. Examples of the water-insoluble dietary fiber include crystalline cellulose, soybean dietary fiber, wheat bran, corn fiber and beat fiber.

The nutritional composition of the invention may comprise vitamins and minerals in amounts according to standard liquid foods. The vitamins include vitamin B₂Nicotinamide, vitamin B₆Calcium pantothenate, folic acid, vitamin B₁₂Vitamin A fatty acid ester, vitamin D₃Alpha-tocopherol, vitamin K₂L-ascorbic acid sodium salt and beta-carotene. Minerals include calcium, phosphorus, iron, sodium, potassium, chlorine, and magnesium, as well as naturally occurring trace elements, e.g., yeast minerals such as copper, zinc, copper, manganese, and chromium. Copper gluconate and zinc gluconate may also be used.

The osmotic pressure of the nutritional compositions of the present invention is from about 300 to 1000mOsm/L, for example from about 300 to 750 mOsm/L. The viscosity of the nutritional composition is preferably from about 5 to 40 mpa.s, in particular from 5 to 20 mpa.s, when measured at room temperature.

The preferred calorie content of the nutritional composition is from about 0.7 to 3 kcal/mL, specifically from 1 to 1.5 kcal/mL.

The nutritional composition is preferably in a directly usable form. The composition in this form can be administered from the nose-stomach and then the jejunum via a test tube or orally. The nutritional composition can be in various forms such as juice beverage or milk shake beverage. The nutritional composition may be a soluble powder that is reconstitutable prior to use.

The nutritional composition may include various flavors (e.g., vanilla), sweeteners, and other additives. Artificial sweeteners aspartylphenylalanine methyl ester and the like can be used.

The edible vanilla extract has a fecal taste reducing effect and may be added in an amount of 5 to 500mg (0.005 to 0.5%) and carotenoid preparations (e.g., alpha-carotene, beta-carotene, lycopene and lutein) may be added in an amount of 10 to 200 μ g (0.00001 to 0.0002%) for fortification.

Antioxidant catechol or polyphenol may be added.

The nutritional composition may be prepared, for example, by mixing the protein, lipid, and carbohydrate in the mixing ratios described above. In this case, an emulsifier may be added to the mixture.

The nutritional composition of the invention may be obtained as a product in a manner known in the art, for example by pre-heating to sterilize a liquid nutritional composition and then sterilizing the filled container with it (ex. using the UHT sterilization and aseptic packaging process), or by filling a container with a liquid nutritional composition and then heat sterilizing the composition with the container (ex. autoclave process).

The homogeneous composition is filled into cans, followed by autoclave, intended to be used as a liquid product; or heated at about 140 to 145 deg.C for about 5 to 8 seconds, sterilized again, cooled, and then sterilized and filled into containers. For using the product as a powder, the homogeneous composition is for example spray dried. For use as a solid, agar or the like is added to solidify the composition.

The nutritional composition of the present invention is useful for nutritional regulation and control of blood glucose levels in patients with diabetes or abnormal glucose metabolism or for the prevention of obesity. More specifically, it helps to regulate the nutrition of patients suffering from type I diabetes, type II diabetes, glucose intolerance, post-operative glucose tolerance diseases and impaired glucose tolerance. It also helps control their blood glucose levels. The nutritional composition is also used in patients at risk of hyperglycemia recurrence or as a supplement to the dietary treatment of diabetic patients. It is also effective in preventing obesity, which becomes a risk factor for additionally inducing diabetes.

In the field of neurosurgery, many patients suffer from perceptual disorders and are unable to eat automatically. If such patients are 40 years old or older, they often suffer from some complications. For these conscious patients, nutrition can be administered through the intestine, which is a more physiological route of food intake, since their absorptive capacity is often not impaired. The nutritional composition of the invention therefore plays an important role in the regulation of nutrition. In patients with Multiple Organ Disease (MODS) having renal failure as well, water and electrolysis abnormality tends to occur, resulting in the hindrance of enteral nutrition from the early stage. There is therefore a need for a designed liquid nutritional composition and at the same time taking care of water electrolysis in renal failure. The nutritional compositions of the present invention are also contemplated as such compositions.

It has been pointed out that blood glucose levels and insulin secretion are drastically increased not only in diabetic patients but also in healthy persons after eating, and visceral fat accumulation is promoted, presumably to induce life-style related diseases such as hyperlipidemia, hypertension and arteriosclerosis. Therefore, the preparation of a meal in view of postprandial blood glucose level control is the basis of dietary therapy for diabetes, which is also important for the prevention of life-style related diseases. The nutritional compositions and oral or tube fed nutrition of the present invention may be used as a diet for treating a diabetic patient in the home, a diet for preventing obesity or a food with health requirements (a food for specific health purposes and a food for nutritional functional use).

Administration of nutritional compositions to patients depends on their status, weight or age, or whether the composition is the sole nutrient. The dosage is determined by the attending physician. When the nutritional composition is used as a supplement to another food, the daily dosage is reduced, depending on the amount of the other food.

The nutritional composition of the invention may be administered multiple times a day, for example from two to five times to the amount necessary for a day, once per day, or for a continuous period of time.

It can be applied after solidification by adding agar to a liquid nutritional composition or by adding water and agar to a powdered nutritional composition and cooling after heat treatment. The solidified nutritional composition may replace ordinary solid foods because it produces a feeling of fullness at the meal.

Examples

The present invention is described more specifically by examples and experiments below. However, the present invention is not limited to or by these examples.

Example 1

Liquid nutritional compositions were prepared according to the raw material amounts shown in table 1 below. The resulting composition had a calorie content of 100kca/100mL and contained protein, lipids and carbohydrates with energy percentages of 23.7%, 30.2% and 46.1%, respectively. The percentage of oleic acid in lipids was 70% and isomaltulose in carbohydrates was 69%. The composition was used as a nutritional composition in the test.

Milk Protein Concentrate (MPC) (product of Fonterra/New Zealand), caseinate of DMV, milk phospholipids (product of New Zealand Dairy Ingredients Co., Ltd.), slightly digestible dextrin (product of Matsutani Chemical Industry), high oil sunflower oil (product of NOF Co., Ltd.) (oleic acid content 80%), perilla oil (product of NOF Co., 6% palmitic acid, 2% stearic acid, 19% oleic acid, 12% linoleic acid and 60% alpha-linolenic acid), and isomaltulose (product of Shin Mitsui Sugar) were used.

TABLE 1

Composition (I)	Raw materials	In 100g of base mixture
			Protein	Milk Protein Concentrate (MPC) caseinate	5g1g
Lipids	Nutrition-modified oil or fat (containing 10% perilla oil), milk phospholipid, soybean lecithin	3.0g0.1g0.3g
			Carbohydrate compound	Isomaltulose maltodextrin xylitol	8g3g0.9g
Dietary fiber	Slightly digestible dextrin	1.6g
			General ingredients	Spice citric acid (for pH adjustment)	0.5g0.2g

Vitamin preparation	Vitamin A fatty acid ester vitamin D3Alpha-tocopherol (alpha-TE) bibenzoyl thiamine hydrochloride vitamin B2Vitamin B6Vitamin B12Nicotinic acid, pantothenic acid, folic acid, vitamin C and vitamin K2Alpha-carotene beta-carotene lycopene lutein	1.3g0.005mg40mg4.7mg2.6mg3.7mg0.005mg29.4mg9.5mg0.49mg60.6mg0.11mg0.8μg4.2μg1.4μg5.59μg
			Mineral substance	Sodium chloride potassium hydroxide sodium sulfate heptahydrate trisodium citrate dihydrate ferrous sulfate	100mg150mg10mg120mg5mg

Example 2

Liquid nutritional compositions were prepared according to the raw material amounts shown in table 2 below. The resulting composition had a calorie content of 100kca/100mL and contained protein, lipid and carbohydrate at 24%, 30% and 46% energy respectively. The percentage of oleic acid in lipids was 70% and isomaltulose in carbohydrates was 69%. The composition was used as a nutritional composition in the test.

TABLE 2

Composition (I)	Raw materials	In 100g of base mixture
			Protein	Milk Protein Concentrate (MPC) caseinate	3.5g2.4g
Lipids	High oil sunflower oil plus perilla oil milk phospholipid soya bean lecithin	2.91g0.1g0.29g

Carbohydrate compound	Isomaltulose maltodextrin xylitol	7.01g2.45g0.9g
			Dietary fiber	Slightly digestible dextrin	1.88g
General ingredients	Spice vanilla extract citric acid (for pH adjustment)	0.5g0.05g0.13g
			Vitamin preparation	Vitamin A vitamin D vitamin E (alpha-TE) vitamin B1Vitamin B2Vitamin B6Vitamin B12Nicotinic acid, pantothenic acid, folic acid, vitamin C alpha-carotene, beta-carotene, lycopene and lutein	250IU30IU13.1mg0.96mg0.6mg0.4mg1.1μg1.8mg1.2mg75μg91mg0.8μg4.2μg1.4μg5.6μg
Mineral substance	Sodium chloride ferrous sulfate yeast zinc yeast monopotassium phosphate dihydrate citric acid trisodium potassium hydroxide	100mgt5mg2mg5mg20mg100mg00mg

Example 3

Liquid nutritional compositions were prepared according to the raw material amounts shown in table 3 below. The resulting composition had a caloric content of 100kca/100mL and contained protein, lipids, and carbohydrates with energy percentages of 22%, 30%, and 48%, respectively. The percentage of oleic acid in lipids was 70% and isomaltulose in carbohydrates was 69%. The composition was used as a nutritional composition in the test.

TABLE 3

Composition (I)	Raw materials	In 100g of base mixture
			Protein	CattleMilk Protein Concentrate (MPC) caseinate	3.2g2.4g
Lipids	High oil sunflower oil plus perilla oil milk phospholipid soya bean lecithin	2.9g0.1g0.29g
			Carbohydrate compound	Isomaltulose maltodextrin xylitol	8g3g0.9g
Dietary fiber	Slightly digestible dextrin	1.5g
			General ingredients	Aromatic edible vanilla extract	0.4g0.05g
Vitamin preparation	Vitamin A vitamin D Natural vitamin E (alpha-TE) vitamin B1Vitamin B2Vitamin B6Vitamin B12Nicotinic acid, pantothenic acid, folic acid, vitamin C alpha-carotene, beta-carotene, lycopene and lutein	250IU30IU8mg0.6mg0.5mg0.3mg0.9μg1.6mg1.0mg50μg45mg0.8μg4.2μg1.4μg5.6μg
			Mineral substance	Sodium chloride potassium hydroxide potassium phosphate monobasic potassium chromium yeast zinc yeast trisodium citrate dihydrate ferrous sulfate	100mg100mg20mg2mg5mg100mg5mg

Example 4 (preparation of a powdered nutritional composition)

In an evaporator, 53kg of liquid nutritional composition prepared according to the raw material amounts shown in table 3 above was concentrated to 32 kg. The resulting concentrated nutritional composition was treated with a spray dryer (exhaust temperature: 95 ℃, pore size 74, core size 17) to obtain 10kg of a powdered nutritional composition. Meibalance C (Table 4) and Glukerna (Table 5) were treated in a similar manner to above to obtain control powders. The solids content of the powdered nutritional composition, Glucerna and Meibalance C were 96.78, 95.38 and 96.38, respectively. The energy content per gram of powdered nutritional composition, Glucerna and Meibalance C were 5.6 kcal, 5.5 kcal and 4.6 kcal, respectively.

Table 4: meibalance C

Composition (I)	Raw materials	In 100g of base mixture
			Protein	Milk Protein Concentrate (MPC)	4g
Carbohydrate compound	Dextrin sugar	14.2g0.4g
			Lipids	Vegetable oil	2.8g
Dietary fiber	Slightly digestible dextrin	1g
			Mineral substance	Potassium sodium chloride calcium phosphorus magnesium iron	100mg110mg140mg110mg85mg15mg1mg
Vitamin preparation	Vitamin A vitamin D vitamin E vitamin B1Vitamin B2Vitamin B6Vitamin B12Nicotinic acid, pantothenic acid and folic acid vitamin C	200IU20IU3mg0.15mg0.2mg0.3mg0.6μg1.6mg0.6mg50μg16mg

Table 5: glukerna

Composition (I)	Raw materials	In 100g of base mixture
			Protein	Casein protein	4.2g
Carbohydrate compound	Maltodextrin fructose	6.2g1.7g
			Lipids	Sunflower oil, soybean oil and soybean lecithin	5.56g
Dietary fiber	Soybean polysaccharide	1.4g
			Mineral substance	Potassium sodium chloride calcium phosphorus magnesium iron	156mg93.2mg144mg70mg70mg28mg1.4mg
Vitamin preparation	Vitamin A vitamin D vitamin E vitamin B1Vitamin B2Vitamin B6Vitamin B12Nicotinic acid, pantothenic acid and folic acid vitamin C	352IU28IU3.2mg0.16mg0.18mg0.22mg0.64μg2.12mg0.92mg42μg21.2mg

Example 5 (Process for solidifying the nutritional composition)

2g of Agar ("Agar Quick", trade name, Ina Shokuhin product) was added to 120g of the powdered nutritional composition prepared in example 4, followed by addition of 150mL of hot water (about 60 ℃). The mixture was stirred. The reaction mixture was heat-treated in a microwave oven ("RE-BM 5W", trade name, SAMSUNG product) at a rated high frequency output of 500W for 5 minutes, and then placed in a refrigerator to be cured. The obtained nutritional composition has a calorie content of 672 kcal. This calorie content can be adjusted if desired. The agar content is preferably 0.5 to 2%.

Test 1 (Effect on blood glucose level in Normal rat)

(1) After pre-breeding 5-week-old Spraque-Dawley IGS male rats (Charles River, Japan) for 2 weeks, they were provided for testing as 7-week-old rats. Rats were fasted for 18 hours and then divided into two groups (n-6), one group was administered with the composition prepared in example 1 and the control group was administered with Glucerna, so that the mean blood glucose levels of the two groups were the same.

For both groups, 12.5mL/kg of the composition prepared in example 1 and Glukerna, respectively, were forced to be orally administered through the probe. Gluteal blood glucose levels were measured with a small electrode type blood glucose level monitor ("Antosense II", trade name, Bayer Sankyo product) before (0 min) and 30 min, 60 min, 90 min and 120 min after administration. Glukerna (product of Dynablott) was found to have proteins, lipids and carbohydrates with energy percentages of 16.4%, 49.2% and 34.4%, respectively (255 kcal/250 mL). The results are shown in FIG. 1.

Blood glucose levels in the group increased to about 130mg/dL 30 minutes after administration, while blood glucose levels in the latter group increased only to about 110mg/dL, as measured by changes in blood glucose levels between the Glucerna administration group and the nutritional composition administration group. This indicates that the rise in blood glucose levels is significantly suppressed by the administration of the nutritional composition compared to Glucerna.

(2) After pre-breeding of 6-week-old Spraque-Dawley (SD) male rats (Japan SLC) for 1 week, they were offered for testing as 7-week-old rats. Rats were fasted for 18 hours and then divided into two groups (n ═ 6), one group was administered with the composition prepared in example 2 and the control group with meicane C ("product of Meiji MilkProducts"), so that the mean blood glucose levels of the two groups were the same. Meibalance C has a calorie content of 100 kcal/100 mL and contains proteins, lipids and carbohydrates with energy percentages of 16%, 25% and 59%.

For both groups, 12.5mL/kg of each of the nutritional composition and Meibalance C was administered separately and forced p.o. through the probe. Gluteal blood glucose levels were measured before (0 min) and 30 min, 60 min, 90 min and 120 min after administration. The results are shown in FIG. 2. Values for each group are therefore expressed as MEAN ± standard deviation (MEAN ± SE). Significant differences between groups were detected with the student's t test and values less than 5% were judged significant.

Based on a comparison of time-dependent changes in blood glucose levels between the Meibalance C administration group and the nutritional composition administration group, blood glucose levels in the former group increased to about 140 to 160mg/dL 30 to 60 minutes after administration, while blood glucose levels in the latter group increased to only about 120mg/dL after 30 minutes and to about 140mg/dL after 60 minutes. This indicates that the rise in blood glucose levels is significantly inhibited by administration of the nutritional composition compared to Meibalance C.

Based on the above results, it was found that the nutritional composition of the present invention is effective for significantly inhibiting the postprandial rise in blood glucose level in normal rats, as compared to the conventional liquid foods generally used.

(3) The blood-level-rise inhibitory effect of each nutritional composition prepared in example 3 was studied in normal rats, using Glucerna and Meibalance C as controls. After 6-week-old Spraque-Dawley (SD) male rats (Japan SLC) were pre-bred for 1 week with "CRF-1" (trade name; Oriental Yeast industry product), they were offered for testing as 7-week-old rats. The rats were fasted for 18 hours, and then blood glucose levels in each gluteal vein were measured. They were then divided into three groups (n-6), one group administered with the composition, two control groups one group administered with Glucerna, and one group administered with Meibalance C, so that the mean blood glucose levels in these three groups were identical.

For these three groups, 12.5mL/kg each of the nutritional composition, Glucerna or Meibalance C was forcibly administered p.o. through the probe. Gluteal blood glucose levels were measured before (0 min) and 30 min, 60 min, 90 min, 120 min and 180 min after administration (after administration of the test substance they were food and water deprived). Values for each group are therefore expressed as MEAN ± standard deviation (MEAN ± SE). Significant differences between groups were detected with the student's t test and values less than 5% were judged significant. The results are shown in FIG. 3.

Blood glucose levels in the groups administered with each nutritional composition and Glucerna showed a range of almost from 90 to 130mg/dL from 0 to 60 minutes. The blood glucose level of the Meibalance C administered group increased to about 140 to 160mg/DL after 30 to 60 minutes, thus showing a significant rise relative to the nutritional composition administered group.

The nutritional composition of the present invention shows similar effects to Glucerna in inhibiting postprandial elevation of normal rat blood levels by administration at fasting time in rats.

Test 2 (Effect on streptozotocin-induced blood glucose levels in type I diabetes)

(1) Spraque-Dawley (SD) male rats (Japan SLC) 6 weeks old were pre-bred with a common diet ("CRF-1", trade name: Oriental Yeast Industry product) and provided for testing as 7 weeks old rats. Streptozotocin (STZ) (product of Wako Pure Chemicals) was dissolved in citrate buffer (pH4.5, 0.05M) at a concentration of 14mg/mL, and the resulting solution was injected intraperitoneally at 70mg/5 mL/kg. One week after STZ administration, rats were fed with normal food and water. Starting the next night, they fasted for 18 hours (water not restricted) and then blood glucose levels in the gluteal veins were measured. They were divided into two groups (n-6), i.e., one group was administered with the composition prepared in example 2 and the control group was administered with Meibalance C, so that the mean blood glucose levels of the two groups were the same.

For both groups, 12.5mL/kg (12.5 kcal/kg) of each of the nutritional composition and Meibalance C was forcibly administered p.o. through the probe. Gluteal blood glucose levels were measured before (0 min) and 30 min, 60 min, 90 min, 120 min and 180 min after administration. Meibalance C has a calorie content of 100 kcal/100 mL and contains proteins, lipids and carbohydrates with energy percentages of 16%, 25% and 59%. The results are shown in FIG. 4. Values for each group are therefore expressed as MEAN ± standard deviation (MEAN ± SE). Significant differences between groups were detected with the student's t test and values less than 5% were judged significant.

Based on a comparison of time-dependent changes in blood glucose levels between Meibalance C and the nutritional composition administration group, blood glucose levels were gradually increased to about 350mg/dL in the 60 min former group, while the latter group was at almost the same level, with a small change observed between 60 and 120 min after administration and after 60 min, indicating that blood glucose level elevation was significantly inhibited compared to the former group.

STZ-induced diabetes is an experimental model of insulin-deficiency and exhibits high blood glucose levels by selective destruction of B cells in the pancreas (Steiner, H. et al: Diabetologia, 6, 558, 1970; Hoftiezer, V. and Carpenter, A.M.: Diabetologia, 9, 178, 1973). The effect of STZ on interfering with pancreatic B cells can be modulated by its dose. Hypoinsulinemia and marked hyperglycemic episodes occur when pancreatic B-cells are destroyed and cannot regenerate (Blondel, O. et al: Diabetes, 38, 610, 1989). This disease state is similar to the insulin-dependent type I diabetes (IDDM) disease state.

On the basis of the test results with STZ-induced diabetic rats, it was confirmed that the nutritional composition of the present invention is also effective for reducing the increase in blood glucose level in insulin-deficient type I diabetes, compared to the existing ordinary liquid diet.

(2) Spraque-Dawley (SD) male rats (Japan SLC) 6 weeks old were pre-bred for 1 week with a common diet ("CRF-1", trade name; product of Oriental Yeast Industry), and provided for testing as 7-week old rats. Streptozotocin (STZ) (product of Wako Pure Chemicals) was dissolved in citrate buffer (pH4.5, 0.05M) at a concentration of 14mg/mL, and the resulting solution at 70mg/5mL/kg was injected intraperitoneally into rats. Seven days after STZ administration, rats were fed with normal food and water. Starting the next night, they fasted for 18 hours (water not restricted) and then blood glucose levels in the gluteal veins were measured. They were divided into three groups (n-6), one group administered with the composition prepared in example 2 and two control groups administered with Glucerna and Meibalance C, so that the mean blood glucose levels in these three groups were identical (260 to 270 mg/dL).

For these three groups, 12.5mL/kg (12.5 kcal/kg) of each of the nutritional compositions, Glucerna or Meibalance C was forcibly administered p.o. through the probe. Gluteal blood glucose levels were measured before (0 min) and 30 min, 60 min, 90 min, 120 min and 180 min after administration. Values for each group are therefore expressed as MEAN ± standard deviation (MEAN ± SE). Significant differences between groups were detected with the student's t test and values less than 5% were judged significant. The results are shown in FIG. 5.

The blood glucose levels of the group to which the nutritional composition was administered showed a small rise 60 minutes after administration, from 270mg/dL to 300mg/dL, remaining at almost the same level up to 120 minutes, and declined to the same level after 180 minutes before administration. The blood glucose levels of the Glucerna administration group showed a similar pattern as the nutritional composition administration group. On the other hand, blood glucose levels in the Meibalance C administered group increased from 270mg/dL to 350mg/dL 60 minutes after administration and decreased to the same level in the nutritional composition or Glucerna administered group 180 minutes later.

In short, the nutritional composition of the present invention inhibits the increase of blood glucose levels in diabetes model animals to a similar extent as in Glucerna, significantly inhibiting blood glucose levels compared to the commercial liquid food Meibalance C. As a result, the nutritional composition of the present invention was proven to be effective for inhibiting the blood glucose level elevation of insulin-deficient type I diabetes (IDDM).

Test 3 (Effect on spontaneous type II diabetes (GK rat))

(1) Male GK rats (CLEA Japan) 5 weeks old were pre-bred for 2 weeks with a common diet ("CRF-1", trade name; an organic Yeast Industry product) and provided for testing as 7 weeks old rats. They were divided into three groups (n-6), i.e., one group administered with the nutritional composition prepared in example 3, and two control groups were a Glucerna administration group and a Meibalance C administration group, so that the average blood glucose levels of the three groups were the same.

After the rats had fasted for 18 hours, 12.5mL/kg of each of the nutritional composition, Glucerna and Meibalance C was forcibly administered p.o. through the probe. Hip blood glucose levels were measured before and 30, 60, 90, 120 and 180 minutes after administration. Values for each group are therefore expressed as MEAN ± standard deviation (MEAN ± SE). Significant differences between groups were detected with the student's t test and values less than 5% were judged significant. The results are shown in FIG. 6.

Blood glucose levels in both the nutritional composition-administered group and the Glucerna-administered group showed a slow increase from about 100mg/dL to 150mg/dL within 30 minutes after administration, and remained at about 150mg/dL until 120 minutes thereafter. Therefore, no significant difference was observed between these groups. Blood glucose levels in the Meibalance C-administered group increased to about 210mg/dL after 60. The blood glucose levels in the meiblance C administered group showed a significant increase compared to the nutritional composition and Glucerna administered group, which lasted up to 120 minutes.

GK rats are spontaneous diabetes model animals obtained by selective breeding of Wister rats aimed at reducing glucose tolerance (Goto y. et al: proc. jap. acad., 51: 80, 1975; Goto y. et al: Tohoku j. exp. med., 119: 85, 1976). Obesity was not found in these rats, but hyperglycemia was found to reduce glucose tolerance and glucose-stimulation reduced initial insulin secretion (Goto y. kakizaki. m.: proc. jap. acad., 57: 381, 1981; Kimura k. et al: Tohoku j. exp. med., 137: 453, 1982; Toyoto t. et al: Diabetes, 14: 319, 1987; Sugiyama Yasuo et al: Diabetes 32: 593, 1989). Their morbidity is very similar to that of human non-dwarf non-insulin dependent type II diabetes mellitus and they are therefore used as animal models for NIDDM.

The nutritional composition of the present invention significantly inhibited the rise of blood glucose levels, and in addition, when ordinary liquid food was orally administered to GK rats, it was observed that its inhibition degree was almost similar to Glucerna. This indicates that the nutritional composition of the invention contributes to the nutritional regulation and control of blood glucose levels in type II diabetes, which accounts for 95% of all diabetic cases.

The above test results confirm that the nutritional composition of the present invention has characteristics different from conventional nutritional compositions, and that blood glucose levels slowly rise after ingestion, and that the increase in blood glucose levels is inhibited and lipid metabolism is promoted by acting on insulin-deficient type I diabetes and insulin-resistant type II diabetes.

Test 4 (Effect on spontaneous type II diabetes by Long-term administration)

As test animals, 7-week-old C57BL/KSJ-db/db Jc1 mice (male) (from CLEAN Japan) were purchased. The mice were used as 8-week-old mice after 1-week acclimatization with a common diet ("CRF-1", trade name; Oriental Yeast Industry product). Blood glucose levels and HbAlc were measured in mice fed with ordinary food ("DCA 2000 System", trade name; Bayer Medical product). They were subsequently divided into three groups (n-8), namely a powdered nutritional composition administration group, a Glucerna powder administration group and a Meibalance C powder administration group, so that the mean blood glucose levels of these three groups were identical (the classified values were considered to be 0-day values). The next day after classification, starting 9 weeks, the three groups were fed with water ad libitum, the nutritional composition prepared in example 4, Glucerna and Meibalance C powder, respectively, without ordinary food. The energy intake for each group was calculated from the intake of each nutritional composition, Glucerna and Meibalance C.

After ad libitum feeding, blood glucose levels and hemoglobin alc (HbAlc), which are indicators of the diabetic condition, were measured periodically (1 time/week at 2:00 to 4:00 pm). HbAlc is hemoglobin that binds glucose. In humans, blood glucose levels represent instantaneous values when blood is collected. On the other hand, HbAlc reflects blood glucose level control 1 to 3 months prior to the time of blood collection, and is thus useful for medical devices to detect and judge the appropriateness of long-term glycemic control.

After the mice were fed ad libitum for 9 weeks, they were fasted for 18 hours (water only without restriction). They were then anesthetized with diethyl ether, followed by blood collection and dissection. Serum was separated from blood and serum GPT was measured using "DRI-CHM 3500" (trade name; product of FUJI FILM). The liver was excised and lipids extracted therefrom according to the method of Folch et al. Neutral fat accumulation in the liver was quantitatively analyzed as a lipid component by "Iatroscan" (trade name; product of Iatro laboratories, Inc.). As the main developed solution, a 50: 20: 2.5 mixture of chloroform, methanol and water was used, while as the second developed solution, a 60: 5: 0.15 mixture of hexane, diethyl ether and formic acid was used.

The measurements are expressed as MEAN ± standard deviation (MEAN ± s.d.). Differences between the three groups of less than 5% were judged significant according to the Mann-Whitney U test.

< results >

The intake energy of the nutritional composition group showed almost stable change for 9 weeks. On the other hand, the intake energy of the Glucerna group was gradually decreased at 3 weeks after the start of intake, the intake energy of the Meibalance group C was decreased at 4 weeks after the start of intake and the level was the same as that of the Glucerna group from 5 weeks to 8 weeks. The weight change over 9 weeks is shown in figure 7.

The nutritional composition and Glucerna powder intake group showed a higher weight gain trend during this period than the Meibalance C powder intake group.

The blood glucose levels of the nutritional composition and Glucerna powder intake group showed similar changes. Blood glucose levels did not change from about 500mg/dL for about 4 weeks, which was the same as before the start of intake. On the other hand, blood glucose levels of the Meibalance C intake group increased around 1 week after the start of intake and were very high after 3 to 4 weeks compared to the nutritional composition. The results are shown in FIG. 8.

In all groups, HbAlc showed an increasing trend until day 17 and thereabouts. At day 24, HbAlc of the nutritional composition group was very low compared to the Meibalance C group, and at day 31 HbAlc of the nutritional composition group was very low compared to Glucerna and Meibalance C groups. The results are shown in FIG. 9.

At week 5, blood glucose levels in the meibatance group C exceeded measurable limits. At week 6, the measurements were stopped because both the blood glucose levels and HbAlc of the Glucerna and Meibalance C groups exceeded measurable limits.

After 9 weeks of feeding each powder and subsequent overnight fasting (18 hours), the mice were blood collected and dissected. Serum GOT and GPT, neutral fat accumulation in liver was measured. GOT and GPT of the Glucerna group showed significantly higher values relative to the nutritional composition group and the Meibalance group C. The results are shown in FIGS. 10 and 11.

Even from visual observation, the livers of the Glucerna intake group became significantly fatty livers, whereas no specific change was found in the livers of each nutritional composition and the Meibalance group C. The neutral fat accumulation in the liver and the amount of neutral fat per g liver were significantly higher in the Glucerna intake group compared to the nutritional composition group and the Meibalance C intake group. The results are shown in FIGS. 12 and 13.

The C57BL/KSJ-db/db Jc1 mouse was found in 1996 in the C57BL/KSJ clone, which was obtained as a mutant type mouse from a C57BL/6J mouse, spontaneously showing significant diabetic symptoms such as hyperphagia, obesity and hyperinsulinemia. These mice are obese diabetic mice exhibiting type II diabetes morbidity. They begin to be obese from 4 to 5 weeks old, and as body weight increases, blood glucose levels begin to increase from 6 to 7 weeks. Obesity is thought to be caused by hyperphagia. They are widely used to analyze the onset mechanism of obesity, diabetes and its complications, and to pharmacologically screen agents for lowering blood glucose levels.

From the results of experiments with these mice it was found that the nutritional composition of the invention is superior to Glucerna for long term glycemic control and lipid metabolism, which is used for nutritional regulation and control of blood glucose levels in patients with abnormal glucose metabolism. For the prevention of chronic complications of diabetes, it is important to maintain appropriate blood glucose levels for a long period of time. According to the report (N.Eng.J.Med.329: 977-.

It was also found that the nutritional composition of the invention has a similar effect on promoting nutritional regulation in patients with abnormal glucose metabolism as Glucerna.

Test 5 (Effect of long-term administration on inhibition of visceral fat accumulation in Normal mice)

As test animals, 4-week-old C57BL/6 Jc1 mice (from CLEA JAPAN) were purchased. They were adapted to 1 week with a common diet ("CRF-1", trade name; Oriental Yeast Industry product) and served as 5 week-sized mice. They were weighed and then divided into three groups (n-9) (the classified weight was considered to be a weight of 0 day), namely a powdered nutritional composition administration group, a Glucerna powder administration group and a Meibalance C powder administration group, so that the weights of the three groups were the same. After classification, they were fed ad libitum with the nutritional composition prepared in example 4, Glucerna and Meibalance C, without ordinary food, and their weight and intake were measured periodically. Blood was collected from their orbital wells under diethyl ether anesthesia into heparin-treated tubes from mice fed ad libitum for 1 month. Blood collection and laparotomy, liver, kidney, spleen, epididymal fat and posterior peritoneal fat were excised and weighed. A cut part of liver was homogenized with 0.5% Triton X-100/0.85% NaCl. The supernatant was collected by centrifugation (1000rpm, 10 minutes). Total cholesterol levels and neutral fat in the supernatant were measured using the cholesterol E-test Wako and the triglyceride test Wako (each product of Wako Pure Chemicals).

Statistical analysis of all data was done using the Mann-Whitney U-test. Results are expressed as mean ± standard deviation. Different letters indicate significant differences and the same letters indicate no significant differences.

In the three groups of nutritional composition, Glucerna and Meibalance C, there was little change in energy intake (conversion from intake) for ad libitum feeding. With respect to weight change, there was little difference in the groups until their growth period, i.e., 5 to 7 weeks old, and these groups showed similar weight increase. From the sexual maturity to the date of test completion, more particularly from 7 to 9 weeks of age, the weight gain of the nutritional composition group was significantly lower than that of the other two groups. The results are shown in FIGS. 14 and 15.

No abnormality was observed in each group of organs by visual observation after 1 month of ad libitum feeding, but the visceral fat amount was significantly different. Visual observation revealed that the visceral fat mass was high to low in the following order: meibalance group C, Glucerna group and nutritional composition group. The nutritional composition group was significantly lower than the Meibalance group C with respect to epididymal fat mass (% by weight) and retroperitoneal fat mass (% by weight). The results are shown in FIGS. 16 and 17. The group of nutritional compositions was shown to be lower but their differences were not significant compared to the Glucerna group. The amount of neutral fat per g liver was almost the same between the nutritional composition, Glucerna and Meibalance group C, whereas the cholesterol level per g liver was significantly lower in the nutritional composition group compared to the Glucerna group and the Meibalance group C.

When the nutritional composition was fed to mice over the growth period of 2 weeks (from 5 weeks to 7 weeks old), the energy intake and weight gain were similar to the Glucerna group and the Meibalance C group fed as controls. This indicates that during the growth phase the nutritional composition has similar nutritional effects as Glucerna and Meibalance C. Although there was no large difference in the energy intake of these three groups from the sexual maturity stage after 7 weeks of age, the weight of the nutritional composition group showed a significantly smaller increase than the Glucerna and Meibalance group C. These results indicate that the nutritional composition has an effect of inhibiting weight gain in mice before the sexual maturity stage, compared to Glucerna and Meibalance group C. Since the amounts of main visceral fat epididymal fat and retroperitoneal fat were lower in the nutritional compositions than in the Glucerna and Meibalance group C, it was concluded that in the nutritional compositions, inhibition of visceral fat accumulation leads to inhibition of weight gain. Blood glucose levels and serum insulin levels proved to be lower than for Meibalance C after intake of the nutritional composition, so it could be called low G.I. (glycemic index) food. The nutritional composition can therefore be used as a diet for the prevention of obesity or as a dietary diet as well as for diabetic patients.

Industrial applications

The nutritional composition of the invention can be used as an oral or tube-fed nutrition, a diet for treating a diet or a diabetic patient at home, a diet for preventing obesity or a food with health requirements, for the nutritional regulation and the control of blood glucose levels in patients suffering from diabetes and glucose intolerance or for preventing obesity. It is useful as a liquid nutritional composition prepared for nutritional regulation, blood glucose level control or prevention of obesity in type I or II diabetic patients, or as a tube feed or enteral nutrient after surgery for patients suffering from severe brain diseases or having brain trauma (hypercatabolism and hypermetabolically induced hyperglycemia) or elderly patients.

Claims (36)

1. A nutritional composition for controlling blood glucose levels, said composition comprising protein, lipid and carbohydrate, wherein the percentage of energy provided by the protein, lipid and carbohydrate is from 10 to 25%, from 20 to 35% and from 40 to 60%, respectively; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

2. The nutritional composition of claim 1, wherein the composition comprises at least one of milk lecithin, soy lecithin, high oil sunflower oil, and perilla oil.

3. The nutritional composition according to claim 1 or 2, wherein the composition is for use in a diabetic or glucose intolerant patient or for the prevention of obesity.

4. The nutritional composition of claim 3, wherein the composition is for use in a diabetic diet at home or a diet that prevents obesity.

5. The nutritional composition of claim 3 wherein the composition is an oral or tube fed (enteral) nutritional.

6. The nutritional composition of claim 3, wherein the composition is a therapeutic diet.

7. The nutritional composition of claim 3 wherein the composition is a health-demanding food.

8. A nutritional composition for preventing obesity, said composition comprising protein, lipid and carbohydrate, wherein the percentage of energy provided by the protein, lipid and carbohydrate is from 10 to 25%, from 20 to 35% and from 40 to 60%, respectively; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

9. The nutritional composition of claim 8 wherein the composition comprises at least one of milk lecithin, soy lecithin, high oil sunflower oil, and perilla oil.

10. The nutritional composition of claim 8 wherein the composition is an oral or tube fed (enteral) nutritional.

11. The nutritional composition of claim 8, wherein the composition is a therapeutic diet.

12. The nutritional composition of claim 8 wherein the composition is a health-demanding food.

13. Use of a nutritional composition comprising protein, lipid and carbohydrate, wherein the percentage of energy provided by the protein, lipid and carbohydrate is from 10 to 25%, from 20 to 35% and from 40 to 60%, respectively, for the manufacture of a nutritional composition for the control of blood glucose levels; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

14. The use of claim 13, wherein the composition comprises at least one of milk lecithin, soy lecithin, high oil sunflower oil, and perilla oil.

15. The use according to claim 13 or 14, wherein the composition is for use in a diabetic or glucose intolerant patient or for the prevention of obesity.

16. The use of claim 15, wherein the composition is for use in a diet at home or for the prevention of obesity in a diabetic patient.

17. The use of claim 15, wherein the composition is an oral or tube fed (enteral) nutritional.

18. The use of claim 15, wherein the composition is a therapeutic diet.

19. The use of claim 15, wherein the composition is a health-demanding food.

20. Use of a nutritional composition for the manufacture of a nutritional composition for the prevention of diabetes, wherein the composition comprises protein, lipid and carbohydrate, wherein the percentage of energy provided by the protein, lipid and carbohydrate is from 10 to 25%, from 20 to 35% and from 40 to 60%, respectively; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

21. The use of claim 20, wherein the composition comprises at least one of milk lecithin, soy lecithin, high oil sunflower oil, and perilla oil.

22. The use of claim 20, wherein the composition is an oral or tube fed (enteral) nutritional.

23. The use of claim 20, wherein the composition is a therapeutic diet.

24. The use of claim 20, wherein the composition is a health-demanding food.

25. A method of controlling blood glucose levels comprising administering a nutritional composition comprising protein, lipid and carbohydrate, wherein the percentage of energy provided by the protein, lipid and carbohydrate is 10 to 25%, 20 to 35% and 40 to 60%, respectively; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

26. The method of claim 25, wherein the composition comprises at least one of milk lecithin, soy lecithin, high oil sunflower oil, and perilla oil.

27. The method of claim 25 or 26, wherein the composition is for use in a diabetic or glucose intolerant patient or for the prevention of obesity.

28. The method of claim 27, wherein the composition is used in a diet of a diabetic patient at home or a diet that prevents obesity.

29. The method of claim 27, wherein the composition is an oral or tube fed (enteral) nutritional.

30. The method of claim 27, wherein the composition is a therapeutic diet.

31. The method of claim 27, wherein the composition is a health-demanding food.

32. A method of preventing obesity, comprising administering a nutritional composition comprising protein, lipid and carbohydrate, wherein the percentage of energy provided by the protein, lipid and carbohydrate is 10 to 25%, 20 to 35% and 40 to 60%, respectively; oleic acid in lipids provides 60 to 90% of the energy, and isomaltulose and/or 1-O- α -D-glucopyranosyl- β -D-fructose in carbohydrates provides 60 to 100% of the energy.

33. The method of claim 32, wherein the composition comprises at least one of milk lecithin, soy lecithin, high oil sunflower oil, and perilla oil.

34. The method of claim 32, wherein the composition is an oral or tube fed (enteral) nutritional.

35. The method of claim 32, wherein the composition is a therapeutic diet.

36. The method of claim 32, wherein the composition is a health-demanding food.