JP5824509B2 - Enteral nutrition - Google Patents

Description

  The present invention relates to an enteral nutrient that maintains an excellent emulsified state even when it comes into contact with gastric juice or intestinal fluid and hardly causes diarrhea.

Two methods of enteral nutrition and parenteral nutrition are known as means of nutritional supplementation for patients whose digestion and absorption functions have declined after surgery or for those whose dysfunction or swallowing function has declined due to illness or age. Enteral nutrition is a method in which nutrients are administered orally via the intestine or by nasogastric tube or gastric fistula, and is considered a more physiological nutrition intake method than parenteral nutrition via blood vessels. It is used when the intestinal function of the patient is effective.
In the enteral nutrition method, enteral nutrients for pharmaceuticals and foods are widely used as nutrition sources to be administered. Since such enteral nutrients are liquid, they are easy to take even by people with reduced mastication and swallowing functions as described above, and pass through a long and thin tube inserted into the stomach and intestine even during tube administration. be able to. Furthermore, there exists an advantage that a nutrient component is easy to absorb even if the patient of the state where the digestion absorption function fell because of being emulsified.
On the other hand, diarrhea is a major problem in the medical field as a trouble when using such enteral nutrients.

If the intestinal tract is not used for a certain period of time, such as when fasting or intravenous nutrition is performed before and after surgery, a kind of waste atrophy may occur in the intestinal mucosa. There are many such cases at the start of enteral nutrition, and diarrhea is thought to occur easily.
When the intestinal tract function is reduced, fat indigestion due to a decrease in digestive enzyme secretion and a decrease in digestion absorption rate increases residues in the intestinal tract, resulting in higher osmotic pressure and a greater amount of water and electrolytes. Diarrhea is likely to occur due to migration to the intestinal tract. In particular, diarrhea is more likely to occur when enteral nutrients with a high lipid content are used.

Patent Document 1 discloses an oral tube feeding composition containing water-soluble dietary fiber and water-insoluble dietary fiber as dietary fibers, and containing an oligosaccharide that is a bifido growth factor, so that diarrhea and constipation are less likely to occur. Has been.
Commercially available enteral nutritional supplements that contain dietary fiber are widely used, but diarrhea may not be adequately controlled even if these enteral nutritional supplements are used. Is still a major issue in the medical field.

JP-A-6-135838

As a result of examining the conventional commercially available enteral nutrients, the present inventors have found that these enteral nutrients are likely to be poorly emulsified when acid addition or salt solution addition is performed. Normally, enteral nutrients manufactured industrially are manufactured in a highly emulsified state, and the emulsified stable state is maintained even during distribution and storage. It is not clear about the stable state of emulsification in the intestines. In other words, if the enteral nutrient is not able to maintain an emulsified stable state when it comes into contact with gastric juice or intestinal fluid in the digestive tract, it may be one of the reasons that diarrhea cannot be prevented.
Accordingly, the present invention provides an enteral nutrient that maintains an excellent emulsified state even in contact with gastric juice or intestinal fluid, and is less susceptible to diarrhea even when digestive absorption function is reduced despite containing lipids. With the goal.

As a result of intensive studies to achieve the above object, the present inventors, as a result of enteral nutrition containing lipid, contain egg yolk lysophospholipid, medium chain fatty acid triglyceride, fatty acid, medium chain fatty acid triglyceride for lipid When the ratio is 20 to 65% by mass, the average particle diameter (volume conversion) when mixed with artificial gastric juice at a ratio of 1: 1 is 10 μm or less, and when mixed with artificial intestinal fluid at a ratio of 1: 1 It was found that enteral nutrients having an average particle size (in terms of volume) of 5 μm or less hardly cause diarrhea despite containing lipids, and the present invention has been completed.
That is, the present invention
(1) Enteral nutrient containing 0.5 to 15% by mass of lipid and having an average particle size (in terms of volume) of 5 μm or less, containing egg yolk lysophospholipid, medium chain fatty acid triglyceride, fatty acid, and medium chain to lipid The ratio of fatty acid triglycerides is 20 to 65% by mass, the average particle size (volume conversion) when mixed with artificial gastric juice at a ratio of 1: 1 is 10 μm or less, and mixed with artificial intestinal juice at a ratio of 1: 1. An enteral nutritional agent having an average particle diameter (volume conversion) of 5 μm or less.
(2) The enteral nutrient according to (1), wherein the content of fatty acid relative to lipid is 0.1 to 5%.
(3) The enteral nutrient according to (1) or (2), which is sealed in a container and subjected to a retort treatment.
(4) Enteral nutrition according to any one of (1) to (3), which is for preventing diarrhea from occurring;
It is.

  According to the present invention, there is provided an enteral nutrient that maintains an excellent emulsified state even when it comes into contact with gastric juice or intestinal fluid, despite containing lipids. Can be prevented.

FIG. 1 (a) shows a photograph of feces when the enteral nutrient obtained using the formulation of Example 7 is given to a partially excised small intestine rat. FIG.1 (b) shows the photograph of the feces when the enteral nutrient obtained using the mixing | blending of the comparative example 6 was given to the small intestine partial excision rat. FIG.1 (c) shows the photograph of feces when the enteral nutrient obtained using the mixing | blending of the comparative example 7 was given to the small intestine partial resection rat.

  The present invention will be described below. In the present invention, “%” means “mass%”.

  The enteral nutrient in the present invention refers to a nutrient used at the time of nutrition supply via the intestine. In general, enteral nutrients may be classified into natural concentrated liquid foods, semi-digested nutrients, ingredient nutrients, etc., depending on the composition, and there are pharmaceuticals and food-treated products. In addition to products with a standard composition with well-balanced daily nutrients based on Japanese dietary intake standards, for liver failure, kidney failure, diabetes, respiratory failure, highly invasive, etc. Some nutritional ingredients are adjusted for specific diseases.

  The enteral nutrient of the present invention contains lipid, egg yolk lysophospholipid, medium chain fatty acid triglyceride and fatty acid.

  Lipids in the present invention are, for example, a series of phospholipids and lysates thereof, neutral fats such as medium-chain fatty acid triglycerides and long-chain fatty acid triglycerides, fatty acids, cholesterols, etc. In addition to the generic names of organic compounds, emulsifiers such as sucrose fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, and polyglycerin fatty acid esters are also included. The amount of lipid contained in the enteral nutrient is preferably 0.5 to 15%, more preferably 2.5 to 10% from the nutritional viewpoint.

  In the present invention, phospholipid refers to diacylglycerophospholipid, and lysophospholipid refers to a monoacyl type in which one acyl group is removed. Examples of lysophospholipids include egg yolk lysophospholipid, soybean lysophospholipid, etc.In the present invention, the use of egg yolk lysophospholipid maintains an excellent emulsified state even when it comes into contact with gastric juice or intestinal fluid, and contains lipid. However, it is possible to provide an enteral nutrient that is unlikely to cause diarrhea even when digestive absorption function is lowered.

  The egg yolk lysophospholipid in the present invention can be obtained by, for example, a method of subjecting a phospholipid obtained by extraction from the egg yolk of poultry eggs such as chicken, quail and duck to an enzyme treatment with phospholipase A by a conventional method.

  The egg yolk lysophospholipid content of the enteral nutrient according to the present embodiment may be appropriately adjusted according to the amount of lipid, but from the viewpoint of maintaining a stable emulsified state, the content is 0.3 to 10% with respect to the lipid. Preferably, 0.5 to 5% is more preferable.

  In the present invention, the medium-chain fatty acid triglyceride is a triglyceride composed of a fatty acid having 6 to 12 carbon atoms. Normally, when a long-chain fatty acid having 14 or more carbon atoms is absorbed from the digestive tract, it is incorporated into the lipoprotein chylomicron. While medium-chain fatty acid triglycerides are absorbed into the portal vein from the digestive tract and directly to the liver through the lymphatic and vein veins, medium-chain fatty acid triglycerides are fast-absorbed fat to replenish energy during disease states It is used for nutrition management.

  In the enteral nutrient of the present invention, the content of the medium chain fatty acid triglyceride is 20 to 65%, preferably 25 to 45%, with respect to the lipid. Medium chain fatty acid triglycerides are fats that are easily absorbed, so it is usually considered better to be added from the viewpoint of preventing diarrhea, but in the enteral nutrient according to the present invention, medium chain fatty acid triglycerides are within the above range. It is possible to provide an enteral nutrient that maintains an excellent emulsified state even when it comes into contact with gastric juice or intestinal juice, and does not easily cause diarrhea even when digestive absorption function is reduced despite containing lipids. it can. When the content of medium-chain fatty acid triglyceride is less than 20% or more than 65%, the emulsified state in the digestive tract becomes unstable and diarrhea is likely to occur.

  In the present invention, the fatty acid means a fatty acid in which the carboxyl group is not covalently bonded to another functional group. Specifically, capric acid (C10), palmitic acid (C16), stearic acid (C18). And saturated fatty acids such as oleic acid (C18: 1) and linoleic acid (C18: 2).

  The enteral nutrient of the present invention preferably contains 0.1 to 5% of fatty acid based on the amount of lipid. Furthermore, it is more preferable to contain 0.3 to 3% with respect to the amount of lipid. Although the fatty acid contained in normal refined edible fats and oils is 0.05% or less, the enteral nutrient of the present invention contains gastric juice by containing 0.1 to 5% of fatty acid with respect to the amount of lipid. Even when it comes into contact with intestinal fluid, an excellent emulsified state can be maintained. When the ratio of fatty acid to lipid is less than 0.1% or more than 5%, the emulsified state in the gastrointestinal tract becomes unstable and diarrhea tends to occur.

  The fatty acid content in the present invention means that the lipid extracted from enteral nutrients is diluted with chloroform, spotted on a silica rod, developed with a developing solvent, and then the developed lipid is detected with a flame ionization detector ( The ratio of the area occupied by the peak area of the fatty acid in the area of the chromatogram detected by FID) is expressed numerically.

  As a method for measuring the fatty acid content with respect to lipids, lipids in enteral nutrients were extracted with chloroform, chloroform was removed, and the obtained lipids were diluted to 0.1 g / mL, and Iatroscan (Co., Ltd.) A certain amount of spot was spotted on a silica rod for Yatron), developed with a developing solvent, and the proportion of the fatty acid peak area was measured from the chromatogram obtained by detecting the developed lipid with a flame ionization detector (FID). Turned into. For identification of fatty acid peaks, oleic acid was simultaneously developed as a standard.

  The enteral nutrient according to the present embodiment can contain other components as long as the effects of the present invention are not impaired. Other ingredients include proteins such as milk protein, whey protein, albumin, casein, and soy protein, and lipids include long-chain fatty acid triglycerides, cholesterol in addition to the aforementioned egg yolk lysophospholipids, fatty acids, and medium-chain fatty acid triglycerides. Furthermore, synthetic emulsifiers such as sucrose fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester and polyglycerin fatty acid ester, soybean lecithin and the like can also be contained. Examples of the carbohydrate include dextrin, lactose, glucose and the like. Further, the amount of these compounds is not particularly limited, but usually from the nutritional viewpoint, enteral nutrients contain 2 to 10% protein, 0.5 to 15% lipid, and 5 to 30% carbohydrate. That's fine. The lipid-derived energy relative to the total energy is 0.5 to 20% in the enteral nutrient of the present invention. Furthermore, dietary fibers such as cellulose and indigestible dextrin, vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, niacin, pantothenic acid, folic acid, vitamin K, biotin, as long as the effects of the present invention are not impaired. Vitamins such as calcium, magnesium, zinc, copper, iron, manganese, phosphorus, molybdenum, chromium, iodine and the like, electrolytes such as sodium and potassium, fruit juices, fragrances and the like.

  The enteral nutrient according to this embodiment may be a pharmaceutical or a food, and the energy concentration is preferably 0.5 to 2 kcal / mL from the viewpoint of nutritional management.

  Enteral nutrients usually have an average particle size (in terms of volume) of 5 μm or less. Industrially produced enteral nutrients containing lipids are generally adjusted to have a particle size of about 1 μm so that they can be easily digested and absorbed, and prevent separation during distribution and storage. Therefore, the enteral nutrient of the present invention is the same. In the present invention, the lower limit of the average particle diameter of enteral nutrient is not particularly limited, but the average particle diameter is 0.1 μm or more in consideration of industrial productivity.

  In the present invention, the artificial gastric juice is prepared by a method (disintegration test first liquid) according to the 15th revised Japanese Pharmacopoeia provisions. That is, 7.0 mL of hydrochloric acid and purified water were dissolved in 2.0 g of sodium chloride to obtain 1000 mL, and the pH was approximately 1.2.

  In the present invention, the artificial intestinal fluid is prepared by a method (disintegration test second fluid) according to the 15th revised Japanese Pharmacopoeia provisions. That is, a 0.2 mol / L sodium dihydrogen phosphate reagent solution (250 mL) was added with a 0.2 mol / L sodium hydroxide reagent solution (118 mL) and water to make 1000 mL. This liquid is colorless and transparent, and its pH is about 6.8.

  The enteral nutrient in the present invention has an average particle diameter (volume conversion) when mixed with artificial gastric juice at a ratio of 1: 1 from the viewpoint of preventing diarrhea despite containing lipids. Is 10 μm or less, more preferably 2 μm or less. In addition, when mixed with the artificial intestinal juice at a ratio of 1: 1 (volume conversion), it is 5 μm or less, preferably 2 μm or less.

  Regarding the state of enteral nutrients in the stomach and intestine after ingestion in the living body, the emulsion formed in the stomach of a healthy person at the time of digestion and absorption of fats and oils usually has a diameter of 0.5 to 1.0 μm. Since it is said that there is, it is considered that the smaller the particle size, the more smoothly digested and absorbed. Therefore, the smaller the particle size when the enteral nutrient is mixed with artificial gastric juice or artificial intestinal juice, the less likely to cause diarrhea, and although not particularly limited, the particle size of the enteral nutrient at the time of manufacture is as described above. Since it becomes 0.1 μm or more, the particle diameter when mixed with artificial gastric juice or artificial intestinal fluid is also 0.1 μm or more.

  The average particle diameter in the present invention is a value obtained by measurement using a laser diffraction particle size distribution measuring device (trade name “Microtrack MT3300EXII” manufactured by Nikkiso Co., Ltd.). When enteral nutrient is mixed with artificial gastric juice or artificial intestinal juice, weigh 50 mL of enteral nutrient into a beaker, add 50 mL of artificial gastric juice or artificial intestinal fluid, and stir well. The sample is circulated without applying a sound wave, and when the value is stabilized, the particle size distribution is measured and the average particle size is a value in terms of volume converted diameter. The circulating water used for the measurement is tap water. Tap water conforms to the Japan Waterworks Act, and is measured without adding a pH adjuster or surfactant.

  The method for producing the enteral nutrient according to the present embodiment is not particularly limited. For example, an appropriate amount of water is added to and dissolved in protein, carbohydrate, etc., and the above egg yolk lysophospholipid, fatty acid, etc. It can be manufactured by adding and mixing the lipids and emulsifying with a homogenizer or the like.

  The enteral nutrient according to the present embodiment can perform retort sterilization and UHT sterilization. For example, in the case of retort sterilization, after filling a container with an enteral nutrient and sealing, treatment at 105 to 130 ° C. for about 5 to 30 minutes can be performed. Since the emulsified state tends to be worse when the heat damage to the enteral nutrient is larger, the effect of the present invention is more easily achieved by performing retort sterilization than UHT sterilization.

  Next, the present invention will be described in more detail based on examples, comparative examples, and test examples. The present invention is not limited to these.

[Test Example 1]
The enteral nutrients of Example 1, Example 2, Example 3, Example 4, Comparative Example 1, Comparative Example 2, and Comparative Example 3 were produced by changing the type and amount of the emulsifier. In addition, it adjusted with the quantity of vegetable oil so that the total lipid amount might be 10% of the whole mixture. Specifically, after mixing the raw materials shown in Table 1 with a mixer, the mixture was processed with a high-pressure homogenizer, 200 g of this was filled in a polypropylene flexible bag, and retorted at 121 ° C. for 15 minutes.

  Furthermore, Table 1 shows the presence or absence of egg yolk lysophospholipid, the ratio of medium-chain fatty acid triglyceride to lipid, and the lipids for the formulations of Example 1, Example 2, Example 3, Example 4, Comparative Example 1, Comparative Example 2, and Comparative Example 3. The ratio of fatty acid to the amount is shown. In addition, the average particle size (volume conversion) of enteral nutrients prepared from the above blending and the average particle size (volume conversion) when the enteral nutrients were mixed with artificial gastric juice and artificial intestinal juice at a ratio of 1: 1, respectively. The measurement results are shown.

  From the results of Table 1, the enteral nutrient (Examples 1 to 4) containing egg yolk lysophospholipid has a small particle size and maintains an excellent emulsified state when mixed with either artificial gastric juice or artificial intestinal fluid. You can see that On the other hand, when soybean phospholipid was used as an emulsifier (Comparative Example 1), when a synthetic emulsifier was used (Comparative Example 2), or when only egg yolk phospholipid (Comparative Example 3) was used, it was mixed with artificial gastric juice or artificial intestinal fluid. It can be seen that the particle size at the time is large and the emulsified state is poor.

[Test Example 2]
The enteral nutrients of Example 5, Example 6, Example 7, and Comparative Example 4 were produced by changing the ratio of medium chain fatty acid triglycerides. In addition, it adjusted with the quantity of vegetable oil so that the total lipid amount might be 10% of the whole mixture. Specifically, after mixing the raw materials shown in Table 2 with a mixer, the mixture was treated with a high-pressure homogenizer, filled with 200 g of a flexible bag made of polypropylene, and retorted at 121 ° C. for 15 minutes.

  Further, Table 2 shows the presence or absence of egg yolk lysophospholipid, the ratio of medium chain fatty acid triglyceride to lipid, and the ratio of fatty acid to lipid for the blends of Example 5, Example 6, Example 7, and Comparative Example 4. In addition, the average particle size (volume conversion) of enteral nutrients prepared from the above blending and the average particle size (volume conversion) when the enteral nutrients were mixed with artificial gastric juice and artificial intestinal juice at a ratio of 1: 1, respectively. The measurement results are shown.

  From the results of Table 2, the enteral nutrient (Examples 5, 6, and 7) in which the ratio of medium-chain fatty acid triglyceride to lipid is 20 to 65% has a particle diameter when mixed with either artificial gastric juice or artificial intestinal juice. It can be seen that the emulsion has a small and excellent emulsified state. On the other hand, when the ratio of medium-chain fatty acid triglyceride is 75% (Comparative Example 4), it can be seen that the particle size when mixed with artificial gastric juice or artificial intestinal fluid is large and the emulsified state is poor.

[Test Example 3]
The enteral nutrients of Example 8, Example 9, and Comparative Example 5 were produced by changing the blending ratio of the fatty acid mixture. In addition, it adjusted with the quantity of vegetable oil so that the total lipid amount might be 10% of the whole mixture. Specifically, after mixing the raw materials shown in Table 3 with a mixer, the mixture was treated with a high-pressure homogenizer, filled with 200 g of a flexible bag made of polypropylene, and retorted at 121 ° C. for 15 minutes.

  Further, Table 3 shows the presence or absence of egg yolk lysophospholipid, the ratio of medium chain fatty acid triglyceride to lipid, and the ratio of fatty acid to lipid for the blends of Example 8, Example 9, and Comparative Example 5. In addition, the average particle size (volume conversion) of enteral nutrients prepared from the above blending and the average particle size (volume conversion) when the enteral nutrients were mixed with artificial gastric juice and artificial intestinal juice at a ratio of 1: 1, respectively. The measurement results are shown.

  From the results in Table 3, enteral nutrients (Examples 8 and 9) having a fatty acid ratio of 0.1 to 5% with respect to lipids are excellent in small particle size when mixed in either artificial gastric juice or artificial intestinal juice. It can be seen that the emulsified state is maintained. On the other hand, when the fatty acid is not included (Comparative Example 5), it can be seen that the particle diameter when mixed with the artificial intestinal juice is large and the emulsified state is deteriorated.

[Test 4 (Animal test)]
Enteral nutrients (Example 7, Comparative Example 6, and Comparative Example 7) to be administered to rats were prepared by changing the type of emulsifier, the ratio of medium-chain fatty acid triglyceride to lipid, and the ratio of fatty acid to lipid. In addition, the total amount of lipid was adjusted with the amount of vegetable oils and fats so that it might become 2.7% of the whole mixture. Specifically, after mixing the raw materials shown in Table 4 with a mixer, the mixture was treated with a high-pressure homogenizer, filled with 200 g of a flexible bag made of polypropylene, and retorted at 121 ° C. for 15 minutes.

  Further, Table 4 shows the presence or absence of egg yolk lysophospholipid, the ratio of medium-chain fatty acid triglyceride to lipid, and the ratio of fatty acid to lipid for the blends of Example 7, Comparative Example 6 and Comparative Example 7. In addition, the average particle size (volume conversion) of enteral nutrients prepared from the above blending and the average particle size (volume conversion) when the enteral nutrients were mixed with artificial gastric juice and artificial intestinal juice at a ratio of 1: 1, respectively. The measurement results are shown.

  From the results shown in Table 4, the enteral nutrient (Example 7) containing egg yolk lysophospholipid, medium chain fatty acid triglyceride, and fatty acid has a small particle size and an excellent emulsified state when mixed with either artificial gastric juice or artificial intestinal fluid. You can see that On the other hand, an egg yolk lysophospholipid is not blended, the ratio of medium-chain fatty acid triglycerides to the lipid is 20% or less, an enteral nutrient containing no fatty acid (Comparative Example 6) and egg yolk lysophospholipid is not blended, and a fatty acid It can be seen that the enteral nutrient (Comparative Example 7) that does not contain sucrose has a large particle size when mixed with an artificial gastric juice, and the emulsified state is poor.

  In order to reproduce the state in which the digestive absorption function was lowered, a small intestine partially excised rat was prepared and tested. That is, the small intestine of 12 7-week-old male SD rats was excised from about 10 cm below 10 cm below the Triz ligament. After a recovery period of about 5 days, it was divided into test groups of 6 animals, and the enteral nutrients obtained using the formulations of Example 7, Comparative Example 6 and Comparative Example 7 were used for 10 days so that the food intake would be equal. They were fed and observed for the shape of feces during the test period.

FIG. 1 (a), (b), (c) shows the state of feces when the enteral nutrient obtained using the formulation of Example 7, Comparative Example 6 and Comparative Example 7 is given to a partially excised small intestine rat. Shown in In the test group to which the enteral nutrition obtained using the formulation of Example 7 from FIG. 1 (a) was given, a clear improvement in diarrhea was confirmed. On the other hand, diarrhea symptoms from soft stool to watery stool were observed in the test group given the enteral nutrition obtained using the formulations of Comparative Examples 6 and 7 from FIGS. 1 (b) and 1 (c). There was no improvement in diarrhea during the period.

Claims (3)

Enteral nutrient containing 0.5 to 15% by weight of lipid and having an average particle size (volume conversion) of 5 μm or less, containing egg yolk lysophospholipid, medium chain fatty acid triglyceride, free fatty acid, medium chain fatty acid triglyceride for lipid The average particle size (volume conversion) when the ratio of the free fatty acid to the lipid is 0.1 to 5% by mass and the artificial gastric juice is mixed at a ratio of 1: 1. Enteral nutrient, characterized in that the average particle size (in terms of volume) when mixed with artificial intestinal juice at a ratio of 1: 1 is 5 μm or less. The enteral nutrient according to claim 1 , wherein the enteral nutrient is sealed in a container and retort-treated. The enteral nutrient according to claim 1 or 2 , which is used for preventing diarrhea.