TWI726846B - Ghrelin secretion enhancer - Google Patents

Abstract

The present invention relates to a novel ghrelin secretion promoter. In more detail, it relates to a ghrelin secretion promoter containing protein hydrolysate and fermented milk protein as protein, medium-chain fatty acid as lipid, and carbohydrate.

Description

Ghrelin secretion enhancer [Related patent reference]

This patent application is based on the Japanese Patent No. 2014-130143 filed on June 25, 2014 and claims its priority, and the entire disclosure of related previous patent applications is cited as a part of this specification.

The present invention relates to a novel ghrelin secretion promoter.

The reasons that cause people's loss of appetite are those caused by diseases, and some are not affected by diseases. Among them, the loss of appetite not caused by diseases, such as the separation or death of their spouses, retirement and other social factors in the elderly, and the decrease in physical activity due to age, or the decrease in chewing power due to dentures, etc. The factors that cause loss of appetite, worry about the state of insufficient nutrition, and then reduce the body's resistance.

Neuropeptides that promote appetite are known as neuropeptide Y (NPY), orexins, motilin, melanin-concentrating hormone (MCH), and agouti-related proteins (agouti-related proteins). protein: AGRP). In addition, substances that suppress appetite It is known that α-Melanocyte-stimulating hormone (α-Melanocyte-stimulating hormone: α-MSH), corticotropin-releasing factor (CRF), cocaine and amphetamine-regulated transcription factor (cocaine-and amphetamine-regulated transcript: CART) and cholecystokinin (cholesystokinin: CCK), etc. These peptides are related to the control of gastrointestinal motility and physiologically related mechanisms, and are believed to have an impact on energy persistence.

Other peptides that increase appetite are known to be ghrelin. Ghrelin is an intrinsic ligand of growth hormone secretagogue receptor (GHSR), a 28-residue peptide hormone found in the human stomach. There are two main molecular forms of ghrelin, active (acetylated ghrelin) and inactive (des-acyl ghrelin). Active ghrelin has the structural feature that serine at the third position is modified (acetylated) by caprylic acid. This modification is necessary for the expression of ghrelin activity, and active ghrelin also has a growth hormone (GH; growth hormone) secretion promoting effect. It is expected that muscle synthesis through the secretion of GH and prevent aging, and it is also expected to be used in the treatment of dwarfism. In addition, since ghrelin is the only intrinsic eating promoting factor, it is also expected to be used for the treatment of eating disorders (anorexia) through the effect of hyperphagia. And in recent years, non-clinical and clinical research has also found its diversified effects.

In other words, ghrelin has been shown to promote fat accumulation related to the regulation of energy metabolism, inhibit insulin secretion, inhibit brown adipose tissue function, etc., promote digestive tract movement related to the digestive system, and secrete gastric acid The hyperactivity of the pancreas, the hyperactivity of pancreatic exocrine secretion, etc., which are related to the circulatory system, inhibit the expansion of the sympathetic nervous system and blood vessels, increase cardiac contractility, and protect myocardial cells. At present, attempts have been made to apply these various physiological effects in clinical applications, and the treatment of artificial joint replacement surgery, gastrointestinal cancer surgery, eating disorders, functional dyspepsia, cancer cachexia, and chronic Clinical trials of ghrelin administered to patients with heart failure cachexia, chronic renal failure cachexia, and chronic obstructive pulmonary embolism (COPD).

The active ghrelin will quickly become a decaprylated modified inactive ghrelin in the blood. The ghrelin in circulating plasma accounts for more than 90% of the total, reflecting the total secretory function and metabolic status. Inactive ghrelin does not cause growth hormone secretion promotion effect, on the contrary, it antagonizes ghrelin, and inhibits the eating action and the gastric fasting movement which inhibits the movement of the digestive tract. Therefore, if the ratio of active ghrelin/inactive ghrelin is higher, the effect of active ghrelin is higher.

Patent Document 1 clarifies the role of ghrelin in the regulation of appetite and its mechanism of action. In addition, it also describes the use of ghrelin to develop a novel therapeutic agent for low-nutrition symptoms and the development of an agonist using ghrelin. Or antagonist novel eating disorder or metabolic disorder treatment agent.

For example, Patent Document 2 describes that the ingestion of specific sterol saponins such as potato presoap can promote the secretion of ghrelin from ghrelin-secreting cells isolated from the stomach of rats.

On the other hand, in Patent Document 1, when ghrelin and its derivatives are added, it is necessary to separately synthesize a peptide having the same amino acid sequence as human ghrelin. In addition, when used in pharmaceutical preparations, such as patents Document 3, it is necessary to suppress the decomposition of the hydrophobic modification structure of ghrelin to stabilize the ghrelin.

In addition, in Patent Document 2, specific sterol saponins such as potato presoap that can promote the secretion of ghrelin must be separately purified.

Therefore, in order to secrete ghrelin in the body, people with poor appetite must be forced to ingest (administer) ghrelin or a well-known substance that promotes the secretion of ghrelin. There are still physical and/or ingestion methods. Psychological barrier. In the current state of technology, it can be said that novel technical methods that can effectively promote the secretion of ghrelin in the body are still being sought.

[Prior Technical Literature] [Patent Literature]

[Patent Document 1] JP 2010-006823 A

[Patent Document 2] JP 2013-227309 A

[Patent Document 3] International Publication 2003/006349

The present invention aims to provide a novel ghrelin secretion promoting agent. In addition, the present invention does not perform the synthesis and/or isolation and purification of compounds, but provides a novel and safe ghrelin secretion promoter with no side effects in a form that is easy to ingest and can exert the secretion effect of ghrelin in the human body.

In view of the above-mentioned issues, the present invention team conducted dedicated research Later, the following findings were obtained. In other words, it was discovered that by ingesting (administering) a composition containing specific components such as protein, lipid, and carbohydrate, the secretion of ghrelin in the body can be promoted.

That is, the present invention is as follows.

[1] A ghrelin secretion promoter containing protein hydrolysate and fermented milk protein as protein, medium-chain fatty acid and carbohydrate as lipid.

[2] The ghrelin secretion promoter as in [1], which contains protein hydrolysate and fermented milk protein as protein, medium-chain fatty acid-containing fats as lipids, phospholipids and oleic acid-containing fats, and as carbohydrates Of Bala Jintang.

[3] The ghrelin secretion promoter of [1] or [2], wherein the protein hydrolysate is selected from casein, milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin, β-lactoglobulin and protein hydrolysate of the raw materials of lactoferrin.

[4] The ghrelin secretion promoter according to any one of [1] to [3], wherein the protein hydrolysate is a whey protein hydrolysate.

[5] The ghrelin secretion promoter of any one of [1] to [4], wherein the blending amount of the protein hydrolysate is 0.5 to 3 g per 100 ml.

[6] The ghrelin secretion promoter according to any one of [1] to [5], wherein the fermented milk protein is derived from a substance obtained by excreting whey from fermented milk.

[7] The ghrelin secretion promoter of any one of [1] to [6], wherein the fermented milk protein is derived from the use of Lactobacillus Bulgaricus (Lactobacillus bulgaricus), Streptococcus Thermophilus (Streptococcus thermophilus), Or a combination of these, fermented milk after fermenting skim milk.

[8] The ghrelin secretion promoter of any one of [1] to [7], wherein the fermented milk protein is derived from fresh cheese.

[9] The ghrelin secretion promoter of any one of [1] to [8], wherein the blending amount of the fermented milk protein is 0.5-6g per 100ml.

[10] The ghrelin secretion promoter according to any one of [1] to [9], wherein the protein hydrolysate uses whey protein isolate (WPI) from Bacillus licheniformus (Bacillus licheniformus). After protease is hydrolyzed, trypsin from porcine pancreas is used for hydrolysis.

[11] The ghrelin secretion promoter of any one of [1] to [10], wherein the molecular weight of the protein hydrolysate is below 10,000.

[12] The ghrelin secretion promoter of any one of [1] to [11], wherein the blending amount of the carbohydrate is 1 to 15 g per 100 ml.

[13] The ghrelin secretion promoter of any one of [1] to [12], wherein the blending amount of oleic acid in the lipid is more than 25% by weight of the total fatty acid.

[14] The ghrelin secretion promoter of any one of [1] to [13], wherein the blending amount of the medium chain fatty acid is 0.01 to 4 g per 100 ml.

[15] The ghrelin secretion promoter of any one of [1] to [14], wherein the calorie of the preparation is 50 to 150 kcal per 100 ml.

[16] The ghrelin secretion promoter of any one of [8] to [15], wherein the fresh cheese is Quark.

[17] The ghrelin secretion promoter according to any one of [2] to [16], wherein the phospholipid is milk phospholipid.

[18] As the ghrelin secretion promoter of any one of [2]~[17], wherein The blending amount of the phospholipid is 0.01 to 0.5 g per 100 ml.

[19] The ghrelin secretion promoter according to any one of [1] to [18], wherein the medium chain fatty acid is a medium chain fatty acid with 8 to 14 carbon atoms.

[20] The ghrelin secretion promoter of any one of [1] to [19], which is used to promote eating hyperphagia, fat accumulation, inhibit insulin secretion, inhibit brown adipose tissue function, and promote gastrointestinal exercise , Hyperactivity of gastric acid secretion, hyperactivity of pancreatic exocrine secretion, inhibition of the expansion of the sympathetic nervous system, blood vessels, increase cardiac contractility or protect myocardial cells.

The ghrelin secretion promoter of the present invention uses constituent components that have been orally ingested for many years, such as protein, lipid, and carbohydrate, and further uses fermented milk protein as an essential component, so that a refreshing taste derived from fermented milk can be obtained. Therefore, the ghrelin secretion promoter of the present invention can be easily and continuously taken (administered), is safe, and has little risk of side effects. Furthermore, the ghrelin secretion promoter of the present invention can be prepared without performing compound synthesis and/or isolation and purification. Furthermore, by using the ghrelin secretion promoter of the present invention, ghrelin can be secreted in the body, and its accompanying various symptom improvement effects can be exerted. Examples of related effects include, for example, hypereating related to eating and energy metabolism regulation function, promotion of fat accumulation, inhibition of insulin secretion, inhibition of brown adipose tissue function, etc., promotion of digestive tract exercise related to the digestive system, gastric acid The effects of hypersecretion, pancreatic exocrine secretion, etc., related to the circulatory system, inhibit the expansion of the sympathetic nervous system and blood vessels, increase cardiac contractility, and protect myocardial cells.

The protein hydrolysate of the present invention, as described above, can provide a composition containing protein hydrolysate and fermented milk protein as protein; medium-chain fatty acid as lipid; and carbohydrate. In addition, according to a preferred embodiment of the present invention, the ghrelin secretion promoter contains protein hydrolysate and fermented milk protein as proteins; medium-chain fatty acid-containing fats, phospholipids, and oleic acid-containing fats as lipids, and as sugars The quality of palatinate.

The protein hydrolysate system of the present invention can use, for example, casein, whey protein (milk protein concentrate (MPC), whey protein concentrate (WPC), whey protein isolate (WPI), α-lactalbumin, β- Milk-derived raw materials such as lactoglobulin), milk protein concentrate (MPC), and lactoferrin. Even if it is a raw material derived from a protein other than milk, if the effect of this invention is obtained, it can use without a restriction|limiting in particular. The raw material of the aforementioned protein hydrolysate can be modified with amino acid residues as needed, and its functional properties (solubility, viscosity, gelation, thermal stability, emulsification stability, etc.) can also be changed. Characteristics, physiological characteristics, etc.). It can be used as the protein hydrolysate of the present invention by adding enzymes and the like to the raw materials of the aforementioned protein hydrolysate for hydrolysis. Moreover, if the same effect as the present invention can be obtained, a commercially available protein hydrolysate can also be used.

For example, in one form of the protein hydrolysate raw material of the present invention, when whey protein is added to the enzyme for hydrolysis, a general enzyme is used. It is not limited to pepsin, trypsin, chymotrypsin, etc., and other hydrolysis can also be used. Plant-derived proteases (papain, pineapple Protease, kiwifruit protease, etc.), purified enzymes of well-known protein such as proteases derived from microorganisms, crude purified products containing these enzymes, and broken cells containing these enzymes.

For example, in one embodiment of the protein hydrolysate of the present invention, the preparation method of the whey protein hydrolysate is a preparation method constructed in accordance with the following steps (1) to (5).

(1) Whey protein isolate (WPI) containing approximately 90% by weight of dry matter protein is dissolved in water so as to contain 8% by weight of protein. (2) The whey protein was denatured by heating the dissolved WPI solution at 85°C for 2 minutes. The pH of the whey protein solution at this time was 7.5. (3) The hydrolysis of the heat-treated whey protein solution uses the endo-type protease alkaline protease 2.4L (Novozymes company) from Bacillus licheniformus, adding 2 weight to the weight of the whey protein %, and reacted at 55°C for 3 hours. (4) Next, using pig-derived trypsin PTN6.0S (Novozymes), adding 3% by weight to the weight of whey protein, and then reacting at 55°C for 3 hours. The pH of the reaction solution was 7 when the reaction was terminated. (5) The obtained reaction solution was centrifuged at 20,000×g for 10 minutes, and the supernatant was passed through a UF membrane (Millpore Corporation) with a molecular weight of 10,000 as a whey protein hydrolysate.

The blending amount of the protein hydrolysate of the present invention can be based on other ingredients (fermented milk protein as protein, medium-chain fatty acid-containing fats and oils as lipids, phospholipids and oleic acid-containing fats and oils, and palatinose as carbohydrates, etc. ) Content, the morbidity, condition, age, body Adjust the weight, use, etc. appropriately. For example, a preferred example of a protein hydrolysate blending amount is 0.5~3g, 0.75~2.8g, 1~2.5g, 1.25~2.25g, 1.5~2.25g, 1.75~2.25g, 1.6~ 2.25g or 1.6~2.1g. The relative blending amount is particularly preferably that the protein hydrolysate is whey protein hydrolysate.

The source of fermented milk protein of the present invention can be fermented milk (for cow milk, buffalo milk, goat milk, goat milk, horse milk and other livestock milk, and/or combined use of partial skimmed milk and skimmed milk of these milks. , Reduced whole milk, reduced skimmed milk, reduced partially skimmed milk, tallow, tallow and other milk raw materials. Liquid milk prepared with one or more types of milk raw materials, all types of liquid milk that are fermented with lactic acid bacteria and other bacteria). More specifically, as the fermented milk protein raw material of the present invention, yogurt, cheese, etc., can be used for fermenting milk with lactic acid bacteria and/or Bifidella bacteria. One form of the fermented milk protein of the present invention includes, for example, natural cheese after the fermented milk is discharged (reduced) whey, and fresh cheese (quark cheese, mascarpone cheese, cream cheese) that has not been matured. . In addition, Lactobacillus bulgaricus (Lactobacillus bulgaricus) and Streptococcus thermophilus (Streptococcus thermophilus) can be mainly used for the production of fermented milk, but Streptococcus lactis, Streptococcus cremoris, Streptococcus diacetilactis, Enterococcus faecium are not limited to these bacteria. , Enterococcus fecalis, Lactobacillus casei, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus murinus, Lactobacillus reuteri, Lactobacillus brevis, Lactobacillus gasseri, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium breve and other lactic acid bacteria and Bifidobacterium breve. It can also be used in combination with other microorganisms that can be used in the production of fermented milk, such as Propionibacterium (Propionibacterium). The fermented milk protein of the present invention can be prepared with any fermented milk, preferably from the use of quark cheese (Quark), or Lactobacillus Bulgaricus (Lactobacillus bulgaricus), Streptococcus Thermophilus (Streptococcus thermophilus), or a combination of these to make The fermented milk after the fermented skim milk is preferably the fermented milk after the skim milk is fermented with Lactobacillus Bulgaricus and Streptococcus Thermophilus.

The general preparation method of fermented milk protein of the present invention is to sterilize skimmed milk first, and then inoculate lactic acid bacteria (Lactobacillus bulgaricus, Streptococcus thermophilus) at a concentration of 0.5 to 5% (w/w) to ferment. When the pH of the solution reaches about 4.6, due to the formation of curd, a separator can be used as desired to separate the whey by centrifugation, and then cool the obtained curd. An example of the composition of the fermented milk protein of the present invention is that the total solid content is 17-19% (w/w), the protein is 11-13% (w/w), the fat is less than 1% (w/w), Carbohydrate is 2-8% (w/w), lactose is less than 2% (w/w). In addition, coagulation using rennet is also included in the fermented milk protein of the present invention. The mixed culture solution of lactic acid bacteria belonging to Lactococcus, cheese bacteria and Candida albicans species is added to skimmed milk and then cultured, and then the whey is removed, and it is also included in the fermented milk protein of the present invention. In addition, the implementation of the The curd obtained in the same way as the method is cut by a cutting machine, and the whey is separated while heating the solution, which is also included in the fermented milk protein of the present invention. The above-mentioned modulation methods are all applicable to the embodiments of the present invention.

The blending amount of the fermented milk protein of the present invention can be based on other ingredients (protein hydrolysate as protein, medium-chain fatty acid-containing fat as lipid, phospholipid and oleic acid-containing fat, and palatin as carbohydrate The content of sugar, etc.), the disease state, condition, age, weight, use, etc. of the ingested subject are appropriately adjusted. For example, a preferable example of the blending amount of fermented milk protein is 0.5-6g, 1-5g, 1.5-4.5g, 2-4g, 2.5-3.5g, or 2.75-3.25g per 100ml of the preparation. The relative blending amount is particularly preferably that fermented milk protein is derived from quark cheese, or Lactobacillus Bulgaricus, Streptococcus Thermophilus, or a combination of these to make fermented milk protein of fermented milk after fermented skim milk.

As the raw material of the phospholipid of the present invention, one or more of known phospholipid raw materials, such as milk phospholipid, soybean-derived lecithin, and egg yolk lecithin, can be used.

The phospholipids of the present invention can further separate and purify the raw materials from milk, soybeans, eggs and the like. If the effects of the present invention can be obtained, raw materials containing commercially available phospholipids can also be used.

The phospholipid of the present invention is preferably milk phospholipid. Milk phospholipid (also known as milk lecithin) is composed of sphingomyelin (SM), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol ) (PI), Phosphatidylserine It is composed of phosphatidylserine (PS) and lysophosphatidylcholine (LPC), and it is only locally present in the milk fat globule membrane (MFGM). The composition of the phospholipid image of MFGM is described in, for example, the Bulletin of Japan Dairy Technical Association, Vol. 50: pp. 58-91, 2000.

The blending amount of the phospholipid of the present invention can be based on other components (protein hydrolysate as protein and fermented milk protein, medium-chain fatty acid-containing fat and oleic acid-containing fat as lipid, and palatinose as carbohydrate Etc.), the morbidity, pathology, age, weight, use, etc. of the object of ingestion are adjusted appropriately. For example, a preferable example of the phospholipid blending amount is 0.01~0.5g, 0.025~0.4g, 0.05~0.3g, 0.06~0.2g, 0.075~0.2g, 0.07~0.15g, 0.07~ 0.12g, 0.07~0.1g, 0.08~0.15g, 0.08~0.12g or 0.08~0.1g. The relative blending amount is particularly preferably that the phospholipid is milk phospholipid.

As long as the other oil and fat raw materials of the present invention are within a range that does not hinder the effects of the present invention, their sources and types are not particularly limited. For example, after comparing the lipid intake standards of the Ministry of Health, Labour and Welfare with the actual content of lipid intake, it is possible to adjust saturated fatty acids (myristic acid, stearic acid, etc.), monounsaturated fatty acids (oleic acid, etc.), and polyunsaturated The blending amount of fatty acids (linoleic acid, linoleic acid, etc.). Among them, it is difficult to increase the intake of monounsaturated fatty acids only by diet in Japan, and it is better to increase the proportion of monounsaturated fatty acids in the total fatty acids. Therefore, for example, oleic acid, which is a monounsaturated fatty acid, can be blended in the composition of the present invention. The lipid source containing a large amount of oleic acid may include, for example, high-oleic acid sunflower oil with high oleic acid content, Rapeseed oil, olive oil, high oleic safflower oil, soybean oil, corn oil, coconut oil, etc. In addition, the source of lipids containing oleic acid includes, for example, nutritionally prepared fats and oils (Nippon Oil & Fats Co., Ltd.). Sunflower oil, rapeseed oil, olive oil, and mixtures with olive oil can also be used.

The content of oleic acid in the oleic acid-containing grease of the present invention is not particularly limited within a range that does not hinder the effects of the present invention, and is preferably 30% by weight or more, more preferably 40% by weight or more, and most preferably 50% by weight or more.

The blending ratio and blending amount of oleic acid in the preparation of the present invention can be based on other components (protein hydrolysate as protein and fermented milk protein, medium-chain fatty acid-containing fats and phospholipids as lipids, and phospholipids as carbohydrates. The content of larkinose, etc.), the disease state, condition, age, weight, use, etc. of the ingested subject are appropriately adjusted.

With respect to the total fatty acid (composition of the total fatty acid) in the preparation of the present invention, the preferred examples of the blending ratio of oleic acid are 25% by weight or more, 25-95% by weight, 25-90% by weight, 25-80% by weight, 25% by weight. ~70% by weight, 30 to 70% by weight, 30 to 60% by weight, 30 to 50% by weight, or 35 to 45% by weight. Here, "total fatty acids" in the present invention means the total amount of free fatty acids contained in the preparation of the present invention and constituent fatty acids in lipids.

In addition, a preferable example of the blending amount of oleic acid is 0.5~8g, 0.7~7g, 0.8~6g, 1~5g, 1~3g, 1~2.2g, 1.2~4g, 1.4~3g per 100ml of preparation. , 1.6~2g. The relative blending amount is especially high oleic high oleic sunflower oil containing oleic fat.

The medium-chain fatty acid-containing fats and oils of the present invention may include, for example, containing Commercially available mixed oils of medium-chain fatty acid triglycerides (commercially available medium-chain fatty acid oils), etc. In addition, the medium-chain fatty acid of the present invention can be, for example, a medium-chain fatty acid having 8 to 14 carbon atoms (preferably a medium-chain saturated fatty acid), and more preferably, caprylic acid, capric acid, or dodecanoic acid.

In the medium-chain fatty acid-containing oil and fat of the present invention, the content of medium-chain fatty acid is not particularly limited within a range that does not hinder the effects of the present invention, and is preferably 50% by weight or more, more preferably 70% by weight or more, and more preferably 90% by weight Above, 100% by weight is best.

The blending ratio and blending amount of the medium-chain fatty acid in the preparation of the present invention can be based on other ingredients (protein hydrolysate as protein and fermented milk protein, phospholipid as lipid and oil containing oleic acid, and as carbohydrate. The content of palatinose, etc.), the disease state, condition, age, weight, and use of the ingested object are appropriately adjusted.

With respect to the total fatty acids in the preparation of the present invention, examples of preferable blending ratios of medium-chain fatty acids are 5% by weight or more, 5 to 95% by weight, 10 to 90% by weight, 15 to 80% by weight, and 15 to 70% by weight. , 20 to 70% by weight, 20 to 60% by weight, 20 to 40% by weight, or 20 to 30% by weight.

A preferred example of the blending amount of medium-chain fatty acids is 0.01~4g, 0.02~3g, 0.05~2g, 0.08~1.5g, 0.1~1.2g, 0.2~1g, 0.4~0.8g or 0.4~ 0.7g.

In terms of lipids in the preparation of the present invention, it is preferable to further contain fats and oils containing polyunsaturated fatty acids. The polyunsaturated fatty acid of the present invention can use, for example, a polyunsaturation with a carbon number of 18 to 24 and an unsaturation degree of 2 to 8. The fatty acid is preferably a polyunsaturated fatty acid with 18-22 carbons and an unsaturation of 2-8, more preferably a polyunsaturated fatty acid with 18-22 carbons and an unsaturation of 2-6, including sub Sesame oil, linolenic acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid and other well-known fatty acids. For example, commercially available purified fish oil containing the aforementioned fatty acids including DHA and EPA can be used as a raw material for polyunsaturated fatty acids.

The blending ratio and blending amount of polyunsaturated fatty acids can be based on other ingredients (protein hydrolysate as protein and fermented milk protein, medium-chain fatty acid oil as lipid, phospholipid and oil containing oleic acid, and as carbohydrate. The content of palatinose, etc.), the disease state, condition, age, weight, and use of the ingested object are appropriately adjusted.

With respect to the total fatty acids in the preparation of the present invention, examples of preferable blending ratios of polyunsaturated fatty acids are 25% by weight or more, 25 to 90% by weight, 25 to 80% by weight, 25 to 70% by weight, and 30 to 70% by weight. % Or 30~60% by weight. In addition, other preferable examples of the blending ratio of polyunsaturated fatty acids are 10% by weight or more, 10 to 70% by weight, 10 to 60% by weight, 10 to 50% by weight, 10 to 40% by weight, and 10 to 30% by weight. %, 15-30% by weight or 15-20% by weight.

A preferable example of the blending amount of polyunsaturated fatty acids is 0.01~5g, 0.02~4g, 0.05~3g, 0.08~2g, 0.1~1g, 0.15~2g, 0.2~1g, 0.15~0.5g per 100ml of preparation , 0.2~1g, 0.3~0.8g, 0.4~0.6g, 0.18~0.3g. For the relative blending amount, the raw material of polyunsaturated fatty acids is particularly preferably purified fish oil.

Because the above-mentioned medium chain fatty acids and polyunsaturated fatty acids It has a peculiar flavor, etc., especially for people with poor appetite, and it is generally not easy to take it directly. Since the preparation of the present invention contains fermented milk protein as an essential component, the refreshing flavor derived from fermented milk can be felt, and even if it contains a necessary amount of medium-chain fatty acids and polyunsaturated fatty acids, it can be easily ingested.

In terms of lipids, the preparation of the present invention preferably further contains long-chain saturated fatty acids. The long-chain saturated fatty acid of the present invention can be, for example, a saturated fatty acid with a carbon number of 16-24, preferably a saturated fatty acid with a carbon number of 16-22, more preferably a saturated fatty acid with a carbon number of 16-20, and most preferably a saturated fatty acid with a carbon number of 16~ 18 saturated fatty acids. Specific examples of related long-chain saturated fatty acids include well-known fatty acids such as myristic acid and stearic acid.

Relative to the total fatty acids in the preparation of the present invention, examples of preferable blending ratios of long-chain saturated fatty acids are 15% by weight or more, 15-95% by weight, 15-90% by weight, 15-80% by weight, and 15-70% by weight. %, 15-50% by weight, 15-30% by weight, or 15-25% by weight.

In addition, a preferable example of the blending amount of the long-chain saturated fatty acid contains 0.01-5 g, 0.1-1 g, 0.15-0.8 g, 0.18-0.7 g, or 0.35-0.6 g per 100 ml of the preparation.

The raw material of the carbohydrate of the present invention is mainly preferably palatinose. Can replace palatinose or use sugar alcohols (sorbitol, xylitol, mannitol) together with it. For example, when the raw materials are palatinose, commercially available palatinose syrup, reduced palatinose, and palatinose syrup can be used.

The blending amount of the carbohydrate (preferably palatinose) of the present invention can be Based on the content of other ingredients (protein hydrolysate and fermented milk protein as protein, medium-chain fatty acid oil as lipid, phospholipid, and oleic acid oil and fat, etc.), the sickness, condition, age, weight, use, etc. of the ingested object And adjust appropriately. A preferable example of the blending amount of carbohydrates in the preparation of the present invention is 1-15g, 1.5-12g, 2-10g, 3-9g, 4-8g or 5-7g per 100ml of the preparation.

In addition to palatinose, the raw materials of the carbohydrates of the present invention can be blended with well-known carbohydrates for the purpose of nutritional design and preference improvement. In addition, for the purpose of nutritional design and health claims, well-known dietary fiber can be blended. Furthermore, well-known carbohydrates such as dextrin may be blended in order to improve the nutritional design and directivity.

The weight ratio of protein to lipid in the preparation of the present invention is preferably 0.3:1 to 3:1, more preferably 1.4:1 to 2:1.

The weight ratio of protein to carbohydrate in the preparation of the present invention is preferably 1:2 to 1:20, more preferably 1:2 to 1:4.

The weight ratio of lipid to carbohydrate in the preparation of the present invention is preferably 1:3 to 1:7, more preferably 1:4 to 1:6.

Furthermore, the preparation of the present invention can adjust its calorie arbitrarily by appropriately adding protein, lipid, and carbohydrate. For example, a more suitable example of the calorie of the preparation of the present invention is 50~150kcal, 60~140kcal, 70~130kcal, 80~120kcal or 90~110kcal per 100ml of the preparation.

In the preparation of the present invention, the energy ratio (calories) relative to the whole protein, lipid, and carbohydrate preparation, if it does not hinder the effect of the present invention There are no special restrictions within the range, and it can be set almost according to the sixth revision of the nutritional requirements of Japanese people. For example, the energy ratio of protein relative to the whole preparation is 15~25%, and the energy ratio relative to the whole lipid of the preparation is 20~30%, the energy ratio relative to the whole carbohydrate of the preparation is 45~65%.

In the preparation of the present invention, in addition to the above-mentioned protein, lipid, carbohydrate, and dietary fiber, water and well-known raw materials that can be ingested (administered) by humans can be blended. For example, from the viewpoint of suppressing side effects, food ingredients and food additives with more dietary experience can be blended. In addition, the preparation of the present invention may be in various arbitrary forms such as liquid, solid, powder, and gel. Furthermore, the preparation of this invention can be prepared by the manufacturing method of a well-known nutrition composition.

In addition, the preparation of the present invention is preferably constituted in a form of a single oral intake unit. The amount of each component contained in the one-time oral intake unit of the present invention can be set, for example, based on the blending amount of each component described above.

Furthermore, the preparation of the present invention is preferably provided in a packaged form in a single oral intake unit. The packaging form of each oral intake unit unit may include a form in which a certain amount is limited by a package, container, etc., and the surface of the packaging may also be accompanied by a component label and a use label for the oral intake. Examples of preferable packaging forms of related units include nutritional supplements, pharmaceutical preparations, and the like.

The preparation of the present invention can be more expected to have an effect by continuously ingesting. A preferred example of the preparation intake plan of the present invention includes a person weighing 60 kg, 200 ml or more per day, 400 ml or more per day, It is 600ml or more per day, 800ml or more per day, 1000ml or more per day, 1200ml or more per day, 1600ml or more per day, or 2000ml or more per day. In addition, a person weighing 60 kg may be at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 12 weeks, or at least 24 weeks. Furthermore, for example, continuous intake is preferred, once a week, twice a week, 3 times a week, 4 times a week, 5 times a week, 6 times a week, or 7 times a week.

In addition, according to another embodiment of the present invention, the effective amount of the composition containing protein hydrolysate and fermented milk protein as protein; medium-chain fatty acid as lipid; It is constituted by ingestion and provides a method to promote the secretion of ghrelin. In addition, according to a preferred embodiment of the present invention, the above-mentioned composition contains protein hydrolysate and fermented milk protein as protein; medium-chain fatty acid-containing fats and oils, phospholipids, and oleic acid-containing fats as lipids; and balsam as carbohydrates. Golden candy. In addition, according to a preferred embodiment of the present invention, the aforementioned composition system further contains a polyunsaturated fatty acid as a lipid. In addition, according to a preferred embodiment of the present invention, the above-mentioned method of promoting ghrelin secretion is used for hyperphagia, promotion of fat accumulation, inhibition of insulin secretion, inhibition of brown adipose tissue function, promotion of gastrointestinal movement, and secretion of gastric acid. Hyperactivity, hyperactivity of pancreatic exocrine, inhibits the expansion of the sympathetic nervous system and blood vessels, increases cardiac contractility or protects myocardial cells. In addition, according to a preferred embodiment of the present invention, the above-mentioned method of promoting ghrelin secretion is used for hypereating, promotion of fat accumulation, inhibition of insulin secretion, inhibition of brown adipose tissue function, promotion of gastrointestinal motility, and gastric acid The method of hypersecretion, pancreatic exocrine secretion, inhibition of the expansion of the sympathetic nervous system and blood vessels, increasing the contractility of the heart or protecting myocardial cells.

In addition, according to a preferred embodiment of the present invention, the above-mentioned method for promoting the secretion of ghrelin can be used as a treatment method for the subject. Furthermore, according to other embodiments, the method for promoting the secretion of ghrelin can be used as a non-therapeutic method for excluding medical behaviors. In addition, the "treatment" of the present invention not only treats established diseases and symptoms, but also includes prevention of diseases and symptoms that may be established in the future. In addition, the "effective amount" can be determined based on the intake plan of the ghrelin secretion enhancer.

In the method of the present invention, a composition (agent) that promotes the secretion of ghrelin can be used, and preferably it can be taken orally. In addition, according to a preferred embodiment, the above-mentioned composition can be taken with food.

In addition, according to one embodiment of the present invention, when the ghrelin secretion enhancer is manufactured, the use of a composition containing protein hydrolysate and fermented milk protein as a protein; as a lipid medium-chain fatty acid; and carbohydrate is provided. In addition, according to other embodiments, the purpose is to provide use of a composition containing as a ghrelin secretion promoter, as a protein hydrolysate and fermented milk protein as a protein; as a lipid medium-chain fatty acid; and a carbohydrate composition. Furthermore, according to another embodiment, a composition containing protein hydrolysate and fermented milk protein as a protein; a medium-chain fatty acid as a lipid; and a carbohydrate composition for promoting the secretion of ghrelin is provided. In addition, according to a preferred embodiment of the present invention, the above-mentioned compositions all contain protein hydrolysate and fermented milk protein as proteins; medium-chain fatty acid-containing fats and oils, phospholipids, and oleic acid-containing fats as lipids; and carbohydrate-containing fats and oils. Larkin candy. In addition, according to a preferred embodiment of the present invention, any of the aforementioned compositions may further contain polyunsaturated fatty acids as lipids.

In addition, the subject is not particularly limited within a range that does not hinder the effects of the present invention, and it is preferably a mammal, and more preferably a human.

[Example]

The following examples illustrate the present invention in more detail, but the present invention is not limited to these examples. In addition,% in the following examples means% by weight unless otherwise specified. In addition, the units and measurement methods in this manual follow the Japanese Industrial Standards (JIS).

(Test Example 1)

Twenty-four 7-week-old male C57BL/6 mice (SLC Corporation, Japan) were divided into three groups with 8 mice in each group. Specifically, the group of ghrelin secretion enhancer powders of the present invention prepared in advance (ghrelin secretion enhancer group), the group of nutritional composition powders administered to the control group (control group), and the group administered to animals Use standard feed (CRF-1) powder group (CRF-1 group).

The nutritional composition of the ghrelin secretion promoter of the present invention and the nutritional composition of the control group are shown in Table 1. In addition, the blending amounts of protein, carbohydrate, and lipid raw materials are as shown in Table 2. The content of oleic acid in the ghrelin secretion enhancer in the table is 39% of the fatty acid composition.

After allowing each group to freely ingest feed for 2 weeks, blood was collected from a large abdominal vein. Take the blood collection tube using Pefabloc SC (Sigma) containing 1/100 of the blood volume of the protease inhibitor, and mix with light shaking. The blood collection tube was centrifuged at 7000 rpm and 4°C for 2 minutes to separate the plasma. To the obtained plasma, 1N HCl was added in an amount of 1/10 with respect to the plasma, and it was used as the plasma for measuring the ghrelin concentration.

The concentration of ghrelin is to determine the concentration of acetylated ghrelin, which is the active form of ghrelin. The concentration of ghrelin in plasma was measured using an ELISA kit (SCETI company: Active Ghrelin ELISA kit). The plasma was diluted 5 times with the assay buffer and measured, and then the dilution factor was corrected to calculate the ghrelin concentration.

As a result, the concentration of ghrelin in the ghrelin secretion enhancer group was 82.8±37.7 (fmol/ml), the concentration of ghrelin in the control group was 46.9±12.0 (fmol/ml), and the CRF-1 group The concentration of ghrelin is 38.0±18.9 (fmol/ml). From the above results, it can be known that the hunger element points The secretion enhancer group has a significant increase in the blood concentration of activated ghrelin (acetyl ghrelin) compared with the control group and the CRF-1 group.

In addition, the whey protein degradation product in Table 1 was prepared using the above-mentioned sequence of (1) to (5) in this specification. In addition, indigestible dextrin is used for dietary fiber.

The composition of the total fatty acid in the preparation of Table 1 is shown in Table 3.

In addition, Table 4 shows an example of the composition of milk phospholipids in Table 1.

Table 1 shows the blending amounts of oleic acid, medium-chain fatty acids and polybasic fatty acids in the formulations in Table 1.

(Test Example 2)

Forty 9-week-old male C57BL/6 mice (Japan SLC Company) were divided into 4 groups with 10 each. Specifically, it is one of the group of powders of the ghrelin secretion enhancer of the present invention described in Test Example 1 prepared in advance (Ghrelin secretion enhancer group), and the nutritional composition powder of the control group described in Test Example 1 after administration. Group (control group), group of AIN93G powder administered to purified animal feed (AIN93G group), group of AIN93G administered to purified animal feed supplemented with medium-chain fatty acid triglyceride powder (AIN93G+MCT) ( AIN93G+MCT group) for testing. In terms of calories, AIN93G+MCT uses the same calories as the ghrelin secretion promoter of the present invention for the blending amount of medium-chain fatty acids. In addition, the ghrelin secretion enhancer, AIN93G, AIN93G+MCT have the same level of vitamin and mineral quality. And in this test example, the nutritional composition and ghrelin secretion enhancer of the control group are shown in Table 1. The same as those shown in Table 2.

The composition of AIN93G and AIN93G+MCT is as follows (Table 6, Table 7).

After allowing each group to take the feed freely for 2 weeks (and fasting for one night), blood was collected from the large abdominal vein. The blood is collected using Pefabloc SC (Sigma) which contains 1/100 of the blood volume of the protease inhibitor Tube, and gently shake to mix. The blood collection tube was centrifuged at 7000 rpm and 4°C for 2 minutes to separate the plasma. To the obtained plasma, 1N HCl was added in an amount of 1/10 with respect to the plasma, and it was used as the plasma for measuring ghrelin concentration.

The concentration of ghrelin is to determine the concentration of the active form of ghrelin. The concentration of ghrelin in plasma was measured using an ELISA kit (SCETI company: Active Ghrelin ELISA kit).

As a result, the concentration of ghrelin in the ghrelin secretion enhancer group was 274±172 (fmol/ml), the concentration of ghrelin in the control group was 89±22 (fmol/ml), and the concentration of ghrelin in the AIN93G group was 274±172 (fmol/ml). The concentration of ghrelin was 76±23 (fmol/ml), and the concentration of ghrelin in the AIN93G+MCT group was 110±56 (fmol/ml). And, the ratio of active ghrelin/inactive ghrelin in the ghrelin secretion enhancer group was 0.75±0.14, and the control group was 0.53±0.16.

In addition, the ghrelin secretion enhancer group has a significant increase in the blood concentration of activated ghrelin (acetyl ghrelin) compared with the control group, AIN93G group, and AIN93G+MCT group.

(Test Example 3)

Patients with colorectal cancer (2) and malignant lymphoma (1) undergoing chemotherapy were given a ghrelin secretion promoter. Specifically, the intake is 600 mL/day 3 days before the start of chemotherapy, and 200 mL/day during the 4 days after the start of chemotherapy and continues for 3 to 4 courses. Measure the concentration of active ghrelin and inactive hunger in the blood before and after the intake of the ghrelin secretion enhancer For the concentration of ghrelin, calculate the ratio of active ghrelin/inactive ghrelin.

As a result, the ratio of active ghrelin/inactive ghrelin before and after ingestion of the ghrelin secretion enhancer increased from 0.137 to 0.206 for one patient with colorectal cancer, and from 0.116 to 0.272 for the other patient with colorectal cancer. . In addition, the number of patients with malignant lymphoma rose from 0.186 to 0.250.

In addition, the average dietary intake (calories consumed) before and one day after the intake of the ghrelin secretion enhancer increased from 1808kcal to 2304kcal for a patient with colorectal cancer, and from 1242kcal to 1624kcal for a patient with malignant lymphoma.

Claims (13)

A use of a composition containing protein hydrolysate and fermented milk protein as a protein, as a lipid medium-chain fatty acid and carbohydrate for the manufacture of a ghrelin secretion promoter, wherein the protein hydrolysate is a whey protein isolate ( WPI) The whey protein hydrolysate obtained by hydrolyzing with endoprotease from Bacillus licheniformus and then hydrolyzing with trypsin from porcine pancreas. The blending amount of the protein hydrolysate is per this The ghrelin secretion enhancer 100ml is 0.5~3g. The fermented milk protein is derived from the fermented milk after the fermented skim milk by using Lactobacillus Bulgaricus, Streptococcus Thermophilus, or a combination of these. The blending amount of the fermented milk protein is 0.5-6 g per 100 ml of the ghrelin secretion promoter. The use of claim 1, wherein the composition contains the protein hydrolysate and the fermented milk protein as the protein, the medium-chain fatty acid, the milk phospholipid and the fish oil as the lipid, and the palatinose as the carbohydrate . The use of claim 1 or 2, wherein the fermented milk protein is derived from a substance obtained by discharging whey from fermented milk. Such as the use of claim 1 or 2, wherein the fermented milk protein is derived from fresh cheese. Such as the use of claim 1 or 2, wherein the cut-off of the protein hydrolysate The flow molecular weight is below 10,000. Such as the use of claim 1 or 2, wherein the blending amount of the carbohydrate is 1~15g per 100ml of the ghrelin secretion enhancer. The use of claim 1 or 2, wherein the blending amount of oleic acid in the lipid is 25% by weight or more of the total fatty acid. Such as the use of claim 1 or 2, wherein the blending amount of the medium-chain fatty acid is 0.01-4 g per 100 ml of the ghrelin secretion enhancer. Such as the use of claim 1 or 2, wherein the calorie of the ghrelin secretion enhancer is 50~150kcal per 100 ml of the ghrelin secretion enhancer. Such as the use of claim 4, wherein the fresh cheese is Quark. Such as the use of claim 2, wherein the blending amount of the phospholipid is 0.01~0.5g per 100ml of the ghrelin secretion promoting agent. Such as the use of claim 1 or 2, wherein the medium chain fatty acid is a medium chain fatty acid with 8 to 14 carbon atoms. Such as the use of claim 1 or 2, wherein the ghrelin secretion promoter is used for hyperphagia, fat accumulation, inhibition of insulin secretion, promotion of gastrointestinal motility, hyperactivity of gastric acid secretion, inhibition of sympathetic nervous system, blood vessel Dilation, increase heart contractility or protect cardiomyocytes.