JP5280194B2 - Gel enteral nutrient and method for preparing the same - Google Patents

Description

  The present invention relates to an enteral nutrient that can be safely and easily ingested by a person with difficulty in swallowing or a patient undergoing tube administration without causing gastroesophageal reflux, and a method for preparing the same. More specifically, a gel enteral nutrient capable of appropriately controlling the physical properties and state of the enteral nutrient in the stomach in a tube feeding method, etc., and a gel for adjusting the viscosity of the gel enteral nutrient The present invention relates to a method for preparing an enteral nutrient.

  The enteral nutrition method is a physiological nutrition administration route that passes through the digestive tract and can solve the problems of the high-calorie infusion method.

  On the other hand, tube feeding is useful for patients with eating / swallowing disorders (such as those with difficulty in swallowing) and is often implemented.

  Tube feeding methods include nasal tube feeding and gastrostomy tube feeding. The gastrostomy tube feeding method is a method of supplying (administering) nutrition into the stomach directly from outside the body through a tube connected to the stomach after performing percutaneous endoscopic gastrostomy (PEG). It is a nutrition management method.

  When enteral nutrition is performed for a long time by the tube feeding method, there are many cases that suffer from complications such as aspiration pneumonia caused by gastroesophageal reflux of liquid nutrient (liquid food).

  On the other hand, there has been reported a method for preventing gastroesophageal reflux by increasing the viscosity (viscosity) by solidifying the liquid nutrient or adding viscosity to the liquid nutrient. That is, the device which solidifies an enteral nutrient with agar or gives viscosity to an enteral nutrient with a trotomy adjuster is made | formed.

  At this time, conventionally, there are insufficient experimental studies on the physical properties and state of enteral nutrients in the stomach, simply solidifying enteral nutrients, or simply adding viscosity to enteral nutrients, It was thought that gastroesophageal reflux did not occur.

  In other words, there are no examples that clearly define the physical properties and conditions of enteral nutrients, taking into account the physical properties and conditions of enteral nutrients inside the stomach. In the enteral nutrition and tube feeding methods, there are no criteria for preparing enteral nutrients with appropriate physical properties.

  JP 2003-201330 A (Patent Document 1) and JP 2003-130230 A describe an enteral nutrient that can easily prevent the enteral nutrient administered to a patient from flowing back from the stomach of the patient toward the esophagus. 2004-26844 (Patent Document 2).

  However, experimental studies are not sufficient on the physical properties and state of enteral nutrients in the stomach when a trolley adjusting agent is used as an enteral nutrient.

  And, for example, when agar is used as a trolley adjusting agent, it is a complicated operation (work) that is preliminarily heated and dissolved in hot water, and this agar aqueous solution is mixed with a liquid nutrient and then cooled in refrigeration for solidification. )is necessary. Moreover, since the agar aqueous solution and the concentrated liquid nutrient are mixed, the liquid nutrient is diluted.

As mentioned above, enteral nutrients and methods for their preparation that have been designed in consideration of the physical properties and conditions of enteral nutrients in the stomach have not existed so far, and their development has been desired. It was.
JP 2003-201230 A JP 2004-26844 A

  The present invention has been made in view of the above-described problems of the prior art, and provides a gel-like enteral nutrient that can be safely and easily ingested by persons with difficulty in swallowing without causing gastroesophageal reflux. Objective. Moreover, it aims at providing the preparation method of the gel-like enteral nutrient which adjusts the viscosity of the said gel-like enteral nutrient.

  In addition, the present invention provides a gel enteral nutrient capable of appropriately controlling the physical properties and state of the enteral nutrient in the stomach in the tube feeding method and the like, and adjusts the viscosity of the gel enteral nutrient It is an object of the present invention to provide a method for preparing a gel enteral nutrient.

  Furthermore, the present invention provides a gel enteral nutrient capable of appropriately controlling the elution (release) state of a protein from a gel enteral nutrient in an aqueous solution having a predetermined pH assuming the stomach, and the gel It is an object of the present invention to provide a method for preparing a gel enteral nutrient that adjusts the viscosity of the enteral nutrient.

  As a result of intensive studies in view of the above problems, the present inventors have found that the elution (release) state of the protein from the gel enteral nutrient in the aqueous solution having a predetermined pH assuming the inside of the stomach is We found that it changed according to the type.

  And, by controlling the type and concentration of the tromis adjusting agent, it was found that the elution (release) state of the protein from the gel enteral nutrient can be appropriately controlled in an aqueous solution having a predetermined pH. It came to be completed.

  Furthermore, the present inventors have found a method for preparing a gel enteral nutrient capable of appropriately controlling the protein elution state from the gel enteral nutrient.

  Such a gel enteral nutrient of the present invention and a method for preparing a gel enteral nutrient capable of appropriately controlling the elution state of a protein from the gel enteral nutrient are particularly, tube feeding methods It is suitable for.

  In the tube feeding method, a drug (antacid) that suppresses secretion of gastric acid may be used.

  The state of the stomach was previously considered to be only about 2 acidic at pH, but when a drug that suppresses the secretion of gastric acid (antacid) is used, the internal state of the stomach is about 7 at pH. May be sex.

  Therefore, in the present invention, an aqueous solution having a pH of 2 and a pH of 7 was prepared as a simulated solution that reproduced the state of the stomach.

  Using these, the pH inside the stomach is simulated to be simulated with acidity and neutrality, and the physical properties of a gel enteral nutrient supplemented with viscosity are experimentally studied.

  In addition, the concept and experimental fact that the effect on gastroesophageal reflux differs depending on the type and concentration of the trotomy regulator are also novel.

  Although there is knowledge about enteral nutrients that can be safely and easily ingested by persons with difficulty in swallowing without causing gastroesophageal reflux, as in the prior art described above, enteral nutrients inside the stomach are known. However, there is no knowledge about enteral nutrients and methods for preparing them that are appropriately controlled.

  In other words, there are no cases in which the physical properties and conditions of enteral nutrients are clearly defined in consideration of the physical properties and conditions of enteral nutrients in the stomach.

  In this regard, the present invention, which simulates the physical properties of gel-like enteral nutrients that simulate the internal pH of the stomach with acidity and neutrality and gives viscosity, is a nutritionist in hospitals, nursing homes, etc. Therefore, it can be used as a criterion for preparing enteral nutrients with appropriate physical properties in enteral nutrition and tube feeding for those with difficulty in swallowing.

  The present invention, which has been completed based on the above findings, is a clear judgment when applying viscosity to liquid compositions containing proteins such as liquid nutrients, enteral nutrients, liquid foods, dairy products, etc. It is extremely useful in that it can provide a reference and, at the same time, provide a enteral nutrient that can be safely and easily ingested by persons with difficulty in swallowing without causing gastroesophageal reflux.

  Gel enteral nutrients of the present invention (for example, liquid foods and pharmaceuticals (medical nutrients, etc.)) include fats and oils, proteins, carbohydrates, dietary fiber, vitamins, minerals, organic acids, It is prepared by adding a tromi adjuster to a conventionally known enteral nutrient containing nutrient components such as organic base, fruit juice, flavors, etc., adjusting its viscosity, and preparing in a gel form, more specifically Is as follows.

[1] In a case where the gel-like enteral nutrient extruded from a syringe and an aqueous solution having a pH of 2 to 7 and a temperature of 25 ° C. are mixed at a weight ratio of 3: 7 immediately after being stirred gently for 5 seconds, A numerical value (elution rate) obtained by dividing the weight of the protein eluted from the gel enteral nutrient in the aqueous solution by the weight of the protein contained in the gel enteral nutrient before mixing is 0 to 0. 2 to be
By adding carrageenan at 0.1 to 3% by weight and / or xanthan gum at 0.2 to 2% by weight with respect to the total amount of the gel enteral nutrient, the viscosity of the gel enteral nutrient is adjusted. Adjust to 100-50,000 cP
A method for preparing a gel enteral nutrient .

[2] and the gel-like enteral nutrient extruded from the syringe, 3 in a weight ratio with an aqueous solution of 25 ° C. temperature is PH2～pH7: after mixing 7, and held for 30 minutes at a temperature of 25 ° C. Later, when gently stirring for 5 seconds, the weight of the protein eluted from the gel enteral nutrient in the aqueous solution is the weight of the protein contained in the gel enteral nutrient before mixing. So that the divided value (elution rate) is 0 to 0.45 ,
By adding carrageenan at 0.1 to 3% by weight and / or xanthan gum at 0.2 to 2% by weight with respect to the total amount of the gel enteral nutrient, the viscosity of the gel enteral nutrient is adjusted. Adjust to 100-50,000 cP
A method for preparing a gel enteral nutrient .

[3] In the case where the gel enteral nutrient extruded from a syringe and an aqueous solution having a pH of 2 to 7 and a temperature of 25 ° C. are mixed at a weight ratio of 3: 7 immediately after being stirred gently for 5 seconds, A numerical value (elution rate) obtained by dividing the weight of the protein eluted from the gel enteral nutrient in the aqueous solution by the weight of the protein contained in the gel enteral nutrient before mixing is 0 to 0. 2 to be
By adding carrageenan at 0.1 to 3% by weight and / or xanthan gum at 0.2 to 2% by weight with respect to the total amount of the gel enteral nutrient, the viscosity of the gel enteral nutrient is adjusted. Adjust to 100-50,000 cP
A method for preparing a gel enteral nutrient for use in tube feeding .

[4] A gel enteral nutrient extruded from a syringe and an aqueous solution having a pH of 2 to 7 and a temperature of 25 ° C. were mixed at a weight ratio of 3: 7, and the temperature was maintained at 25 ° C. for 30 minutes. Later, when gently stirring for 5 seconds, the weight of the protein eluted from the gel enteral nutrient in the aqueous solution is the weight of the protein contained in the gel enteral nutrient before mixing. So that the divided value (elution rate) is 0 to 0.45,
By adding carrageenan at 0.1 to 3% by weight and / or xanthan gum at 0.2 to 2% by weight with respect to the total amount of the gel enteral nutrient, the viscosity of the gel enteral nutrient is adjusted. Adjust to 100-50,000 cP
A method for preparing a gel enteral nutrient for use in tube feeding .

  In the present invention, “gel” is also referred to as “tromy” and is a state that does not cause reflux to the esophagus when administered into the stomach, and includes so-called “sol”. .

  In the present invention, the “protein weight” is a value measured by the Kjeldahl method.

  In the present invention, “slowly stirred for 5 seconds” means, for example, that when the enteral nutrient and the aqueous solution having a predetermined pH are mixed using an airtight container with a head space of 10%, the upper and lower positions of the airtight container are Slowly means to reverse (invert) about twice, for example, once, twice or three times.

  In the present invention, “held” refers to a state of standing after mixing an enteral nutrient and an aqueous solution having a predetermined pH using, for example, a sealed container having a head space of 10%.

  In the present invention, the “tromi-adjusting agent” means an edible one containing a viscous substance such as agar, carrageenan, xanthan gum, locust bean gum, tara gum, guagum and psyllium seed gum.

  In the present invention, “carrageenan” means, for example, a water-soluble polysaccharide extracted from red algae as in agar. The kappa and iota types dissolve in hot water to form a random coil, and cool to form a double helix structure that gels. In order to form a gel, it is necessary to heat in the same manner as agar, but sodium carrageenan is known to hydrate in cold water in a short time.

In the present invention, when carrageenan is added to a conventional enteral nutrient (for example, liquid food) as a tromi adjusting agent to obtain a gel enteral nutrient (for example, liquid food) of the present invention, sodium type Carrageenan is preferably used.
In the present invention, “xanthan gum” means, for example, a polysaccharide produced by a microorganism (Xanthomonas campestris). When dissolved in cold water, it has the characteristic of showing pseudoplastic (pseudoplastic) viscosity.

  According to the present invention, a gel-like enteral nutrient that can be safely and easily ingested by a person with difficulty in swallowing or a patient undergoing tube administration without causing gastroesophageal reflux, and the gel-like enteral nutrient The preparation method of the gel enteral nutrient which adjusts a viscosity can be provided.

  According to the present invention, by adding and mixing carrageenan and / or xanthan gum to a conventionally known enteral nutrient as a trolley adjuster, the gel enteral nutrient of the present invention is prepared. The viscosity of the gel enteral nutrient can be adjusted so that the elution (free) state of the protein from the gel enteral nutrient can be appropriately controlled in a predetermined pH state.

  Thus, according to the present invention, the gel-like enteral nutrient capable of appropriately controlling the physical properties and state of the enteral nutrient in the stomach in the tube feeding method and the like, and the gel-like enteral nutrient The preparation method of the gel enteral nutrient which adjusts a viscosity can be provided.

  Further, according to the present invention, a gel enteral nutrient capable of appropriately controlling the elution (release) state of the protein from the gel enteral nutrient in an aqueous solution having a predetermined pH assuming the stomach, and the It is possible to provide a method for preparing a gel enteral nutrient that adjusts the viscosity of the gel enteral nutrient.

  In the present invention, carrageenan and / or xanthan gum is added to and mixed with a conventionally known enteral nutrient as a tromi adjuster, and protein is eluted from the gel enteral nutrient in a predetermined pH state inside the stomach. The viscosity of the gel enteral nutrient is adjusted so that the (free) state can be appropriately controlled.

  As a result, according to the gel-like enteral nutrient of the present invention, a normal normal stomach condition (for example, acidity of about pH 2) or a drug that suppresses secretion of gastric acid (antacid) was used. In the state of the stomach (for example, neutral pH is about 7), elution of nutritional components (proteins) from gel enteral nutrients can be controlled arbitrarily so that the elution rate does not increase rapidly. .

  If the dissolution rate increases rapidly, a state in which gastroesophageal reflux is likely to occur will appear. However, according to the gel-like enteral nutrient of the present invention and the method for preparing a gel-like enteral nutrient that adjusts the viscosity of the gel-like enteral nutrient, the normal internal state of the stomach ( For example, in a state in the stomach using an agent (antacid) having a pH of about 2) or a gastric acid secretion inhibitor (antacid) (for example, a neutral pH of about 7), the elution rate is kept low, and carrageenan and / or Or enteral nutrients taken into polysaccharides such as xanthan gum, etc., gradually elute with digestive activity, gradually absorbing the nutrients into the body, making it difficult to cause gastroesophageal reflux Can be produced.

  That is, a gel-like enteral nutrient having an appropriate physical property value that can be safely and easily ingested by a person having difficulty in swallowing or a patient undergoing tube administration without causing gastroesophageal reflux, and the gel-like enteral nutrition The preparation method of the gel-like enteral nutrient which adjusts the viscosity of an agent can be provided.

  When the gel enteral nutrient of the present invention is gently stirred for 5 seconds immediately after mixing with an aqueous solution having a temperature of 25 ° C. and a weight ratio of 3 (gel enteral nutrient): 7 (aqueous solution) The value (elution rate) obtained by dividing the weight of the protein eluted from the gel enteral nutrient in the aqueous solution by the weight of the protein contained in the gel enteral nutrient before mixing is 0. It is characterized by being -0.2.

  Immediately after mixing the gel-like enteral nutrient and the aqueous solution having a temperature of 25 ° C. at 3: 7, when the mixture is gently stirred for 5 seconds, Nutritional components such as proteins are easily eluted from enteral nutrients, and the nutritional components tend to cause gastroesophageal reflux.

  On the other hand, even when the elution rate of the nutritional component is 0, the gel enteral nutritional agent incorporated into the polysaccharide of the trotomy adjuster gradually elutes due to the peristaltic movement of the stomach or intestinal tract, It is gradually absorbed into the body.

  As described above, when the gel-like enteral nutrient and the aqueous solution having a temperature of 25 ° C. are mixed at 3: 7 and then gently stirred for 5 seconds, the elution rate of the nutrient component is 0 to 0.2. And normal normal stomach condition (for example, acidity of about pH 2) or stomach condition using a drug that suppresses gastric acid secretion (antacid) (for example, pH of about 7 neutrality) In this case, enteral nutrients incorporated into polysaccharides such as carrageenan and / or xanthan gum are gradually eluted with the activity of digestive organs, and the nutritional components are gradually dissolved in the body. It can be absorbed to create a condition that is unlikely to cause gastroesophageal reflux.

  It should be noted that the normal normal state of the stomach (for example, acidity of about pH 2) or the state of the stomach using a drug that suppresses secretion of gastric acid (antacid) (for example, pH of about 7 is neutral) , The elution rate is kept low, and enteral nutrients incorporated into polysaccharides such as carrageenan and / or xanthan gum are gradually eluted with digestive activity, and the nutrients are gradually absorbed into the body. The elution rate is more preferably 0 to 0.15, still more preferably 0 to 0.1, in order to create a state in which gastroesophageal reflux is unlikely to occur.

  In addition, considering the normal normal state of the stomach, the above-mentioned dissolution rate (preferably 0 to 0.2, more preferably 0 to 0.15, even when the pH of the aqueous solution is in the range of 1 to 8, Preferably, it is 0 to 0.1).

  In the above, gently stirring for 5 seconds means that when the gelled enteral nutrient and the aqueous solution are mixed using a sealed container with a head space of 10% as described above, the vertical position of the sealed container is determined. Slowly reverse (invert) about twice.

  Another gel-like enteral nutrient of the present invention comprises a gel-like enteral nutrient and an aqueous solution having a temperature of 25 ° C. in a weight ratio of 3 (gel-like enteral nutrient): 7 (aqueous solution). After mixing, when the temperature is kept at 25 ° C. for 30 minutes and gently stirred for 5 seconds, the weight of the protein eluted from the gel enteral nutrient is added to the aqueous solution before mixing the gel. The numerical value (elution rate) divided by the weight of the protein contained in the shaped enteral nutrient is 0 to 0.45.

  In the case where a gel enteral nutrient and an aqueous solution having a temperature of 25 ° C. were mixed at a weight ratio of 3: 7, held at a temperature of 25 ° C. for 30 minutes, and then gently stirred for 5 seconds. When the elution rate of the nutrient component is larger than 0.45, the nutrient component such as protein is easily eluted from the gel enteral nutrient, and the nutrient component tends to cause gastroesophageal reflux.

  On the other hand, even when the elution rate of the nutritional component is 0, the gel enteral nutritional agent incorporated into the polysaccharide of the trotomy adjuster gradually elutes due to the peristaltic movement of the stomach or intestinal tract, It is gradually absorbed into the body.

  In this way, the gel-like enteral nutrient and the aqueous solution having a temperature of 25 ° C. were mixed at a weight ratio of 3: 7, and the temperature was kept at 25 ° C. for 30 minutes, and then gently stirred for 5 seconds. In this case, the numerical value (dissolution rate) is obtained by dividing the weight of the protein eluted from the gel enteral nutrient into the aqueous solution by the weight of the protein contained in the gel enteral nutrient before mixing. ) Is 0 to 0.45, the normal normal stomach condition (for example, acidity of about pH 2) or the stomach condition using a drug that suppresses the secretion of stomach acid (antacid) (for example, , PH is about 7), and the elution rate is kept low, and enteral nutrients incorporated into polysaccharides such as carrageenan and / or xanthan gum are gradually eluted along with digestive activity. And gradually absorb the nutrients into the body Te, it is possible to create a state which is hard to cause a gastro-esophageal reflux.

  Even in this case, for the same reason as described above, the elution rate is more preferably 0 to 0.15, and still more preferably 0 to 0.1.

  In addition, considering the normal normal state of the stomach, the above-described dissolution rate (preferably 0 to 0.45, more preferably 0 to 0.15, even when the pH of the aqueous solution is in the range of 1 to 8, Preferably, it is 0 to 0.1).

  In addition, holding | maintenance here means the state which left still after mixing gel-like enteral nutrient and aqueous solution using the airtight container which made head space 10% as mentioned above. .

  The inventors of the present application have completed the present invention by confirming the above-described facts by examples described later.

  According to the gel enteral nutrient of the present invention described above, nutrient components such as protein are eluted from the enteral nutrient in an appropriate time, so that the nutrient components are easily absorbed into the body, and the gastroesophageal tract It will be in the state where it is hard to raise backflow.

  Conventionally, enteral nutrients (for example, liquid foods) were mainly products with an energy amount of about 1.0 kcal / ml at the beginning of development, but due to recent technological innovation, etc. Products are being developed, and in the future, it is thought that the development of ultra-dense products of 2.0 kcal / ml will progress.

  In consideration of the fact that more efficient nutritional supplementation is possible by thickening the liquid food, the amount of energy of the gel enteral nutrient in the present invention is preferably 1.0 kcal / ml or more, more preferably It is 1.5 kcal / ml or more, more preferably 2.0 kcal / ml or more. If less than 1.0 kcal / ml, efficient nutritional supplementation becomes difficult.

  The viscosity of conventionally known enteral nutrients containing nutrients such as fats and oils, proteins, carbohydrates, dietary fiber, vitamins, minerals, organic acids, organic bases, fruit juices, flavors, etc. is about 5 to 100 cP. there were.

  The upper limit of the viscosity of the gel-like enteral nutrient of the present invention prepared by adding a trolley adjuster to this conventionally known enteral-nutrient, adjusting its viscosity, and preparing it in a gel form can be easily achieved with a syringe or the like. Although it will not specifically limit if it is a grade which can be extruded, Preferably it is 100-50,000 cP, More preferably, it is 1,000-20,000 cP, More preferably, it is 2,000-10,000 cP.

  The preferable range of the viscosity is a normal normal stomach condition (for example, acidity of about pH 2) or a stomach condition using a drug (antacid) that suppresses secretion of gastric acid (for example, pH). Is about 7), and the elution rate is kept low, and enteral nutrients incorporated into polysaccharides such as carrageenan and / or xanthan gum are gradually eluted along with digestive activity. It is determined from the viewpoint of gradually absorbing nutrients into the body and creating a state in which gastroesophageal reflux is unlikely to occur.

 If the viscosity of the gel enteral nutrient is too low, it passes through a tube or the like and breaks immediately after being accumulated in the body, resulting in a fragile state. Immediately after passing through the tube, the liquid food (nutrient component) is not retained in the matrix. Since it is not held in the matrix, the portion (aqueous solution) is considered to easily cause gastroesophageal reflux.

 On the other hand, when the viscosity of the gel enteral nutrient is too high, the matrix is hard to break and is in a strong state, but it is difficult to pass through a tube or the like. If the fluidity in the tube is poor, the physical properties are not suitable for tube feeding methods (such as transgastric administration).

  The lipid used for the gel enteral nutrient in the present invention is not particularly limited. For example, vegetable oils such as soybean oil, corn oil, cottonseed oil, perilla oil, coconut oil, rapeseed oil, animal oils such as beef tallow, pork fat, fish oil, etc. Synthetic triglycerides and the like can be used alone or in any combination. And it is preferable that the energy amount of the lipid which occupies for the total energy amount of a gel enteral nutrient is 5 to 40%.

  The protein used for the gel enteral nutrient in the present invention is not particularly limited, and examples thereof include animal proteins such as milk protein and meat protein, plant proteins such as soybean protein, and protein enzymes including peptides and amino acids. Decomposition products and the like can be used alone or in any combination. And it is preferable that the energy amount of the protein which occupies for the total energy amount of an enteral nutrient is 10 to 30%.

  The sugar used for the gel enteral nutrient in the present invention is not particularly limited. For example, oligosaccharides containing monosaccharides such as glucose and fructose, polysaccharides such as starch and dextrin, and disaccharides such as maltose and lactose. Can be used alone or in any combination. And it is preferable that the energy amount of the carbohydrate which occupies for the total energy amount of an enteral nutrient is 30 to 85%.

  Nutritional components used in the gel enteral nutrient in the present invention are not particularly limited. For example, dietary fiber, vitamins, minerals, organic acids, organic bases, fruit juices, flavors and the like may be used alone or in any combination. Can be used.

  The gel-like enteral nutrient of the present invention does not particularly limit the type and concentration of the trolley adjusting agent, but the trolley adjusting agent preferably contains carrageenan and / or xanthan gum.

  That is, each of carrageenan and xanthan gum can be used alone or in combination.

  At this time, the carrageenan is preferably a cold water soluble sodium (Na) type.

  For example, in agar, it is necessary to carry out a complicated operation in which the agar aqueous solution is dissolved in hot water in advance, mixed with liquid food, and then cooled in a refrigerator for solidification. Since the liquid food is mixed, the liquid food is diluted.

  On the other hand, a trolley adjusting agent mainly composed of cold water-soluble sodium-type carrageenan or xanthan gum is preferable because it can be easily mixed with an enteral nutrient at room temperature or refrigerated.

  And as a ratio which mixes carrageenan independently with respect to the whole amount of the gel-like enteral nutrient of this invention, Preferably it is 0.1 to 3 weight%, More preferably, it is 0.3 to 2.5 weight%. More preferably, it is 0.5 to 2% by weight.

  Moreover, it is preferably 0.2 to 2% by weight, more preferably 0.3 to 1.5% by weight as a ratio of mixing xanthan gum alone with respect to the total amount of the gel enteral nutrient of the present invention. More preferably, it is 0.4 to 1% by weight.

  The addition amount and ratio of such carrageenan and xanthan gum are the preferred viscosities (preferably 100 to 50,000 cP, more preferably 1,000 to 20,000 cP, and more preferably) of the aforementioned gel enteral nutrient of the present invention. Is determined from 2,000 to 10,000 cP).

  At this time, when carrageenan and xanthan gum are used in combination, it is clear that the mixing ratio of each can be reduced with respect to the total amount of the enteral nutrient in the form of tromi as compared with the case where each is used alone.

  When carrageenan and xanthan gum are used in combination, the mixing ratio can be arbitrarily set from 99: 1 to 1:99.

  Then, a carrotanan and / or xanthan gum can be used as a main component, and a trolley adjusting agent (viscous substance) such as locust bean gum, tara gum, guar gum, or psyllium seed gum can be used in combination.

  Hereinafter, although an example is given and explained about the present invention, the present invention is not limited by this.

Elution rate of nutritional components from gel-like enteral nutrients in stomach internal simulated liquid Gel-type (tromy) enteral nutrient (in the present specification, “matrix”) ”), The influence of the tromi-adjusting agent (viscosity-imparting agent, viscosity-adjusting agent, viscosity-expressing substance) on the elution rate (elution amount) of the nutritional component (protein) from

  The model gastric juice is composed of an acidic aqueous solution (pH = 2) that is close to the normal normal state inside the stomach and a neutral aqueous solution (pH that is close to the state inside the stomach using a drug that suppresses secretion of gastric acid (antacid)). = 7). The dissolution rate was defined by the following formula.

  That is, elution rate [−] = (weight of protein released into model gastric fluid) / (weight of protein initially contained in enteral nutrient).

  The state of the stomach was experimentally examined by changing the type of trotomy regulator and examining the change in dissolution rate over time. If the dissolution rate increases rapidly, a state in which gastroesophageal reflux is likely to occur will appear.

  On the other hand, when the elution rate is kept low, enteral nutrients taken up in polysaccharides such as the trolley adjuster elute with digestive activity, and the nutrients are gradually absorbed into the body, It will be difficult to cause esophageal reflux.

  As a conventionally known enteral nutrient, liquid food (Meiji Dairies Co., Ltd., lipid: 2.8 wt%, protein: 4 wt%, carbohydrate: 14.5 wt%, dietary fiber: 1 wt%) In addition, carrageenan, Tromake (registered trademark) (manufactured by Meiji Dairies Co., Ltd., main component: xanthan gum (content rate: 33%)) is used as a trolley adjusting agent. A nutrient was prepared.

  In addition, as a comparative example, an enteral nutrient prepared in the same manner except that agar was used as a tromi adjuster was prepared.

  Table 1 shows the composition (composition) of the prepared enteral nutrient.

As model stomach contents, hydrochloric acid / potassium chloride buffer (pH = 2) was used for the acidic aqueous solution, and phosphate buffer (pH = 7) was used for the neutral aqueous solution. Here, the phosphate buffer solution of the neutral aqueous solution simulates (models) the state of the stomach when the antacid is administered.

The specific experimental procedure is as follows.

(1) 70 g of acidic aqueous hydrochloric acid / potassium chloride buffer (pH = 2) and 70 g of neutral aqueous phosphate buffer (pH = 7) were administered to the stomach and antacid, respectively. Used as model gastric fluid inside the stomach. The temperature of the model gastric fluid was about 25 ° C.

(2) 30 g of a gel-like (tromi-like) enteral nutrient prepared with the formulation shown in Table 1 was filled into a plastic syringe (thermo disposable type, capacity: 50 ml). Here, in the preparation of a gel enteral nutrient, agar is dissolved by heating (85 ° C.) in distilled water, and carrageenan and Tromake (registered trademark) are dissolved in distilled water at room temperature. An aqueous solution was prepared. And the aqueous solution of these trolley adjusting agents was added and mixed with the liquid food, and the gel-like enteral nutrient was prepared. The temperature of the gel enteral nutrient was about 25 ° C.

(3) 30 g of the gel enteral nutrient filled in the syringe was added to 70 g of each model gastric fluid (pH = 2 and pH = 7).

(4) When stirring immediately after adding the gel enteral nutrient to the model gastric solution, the top and bottom positions of the sealed container are gently lowered for 5 seconds using a sealed container with a head space of 10%. Reversed twice (inverted). At this time, the main purpose of this experiment is to measure the degree of liquid food (nutrient component) held in the tromy enteral nutrient (matrix). Therefore, in the first embodiment, the reverse (reversal) operation is performed for the purpose of making the portions other than the matrix uniform without assuming the peristaltic motion of the stomach or intestine. It left still using the airtight container which made head space 10%. The holding temperature was 25 ° C.

(5) On the other hand, in Example 2 which will be described later, an operation assuming a peristaltic movement of the stomach or intestine was performed. That is, in Example 2, it was held while shaking. At this time, the shaking condition was 120 times / minute with an amplitude of about 35 mm. In Example 1, the temperature was 25 ° C. (normal temperature), whereas in Example 2, the temperature was 37 ° C.

(6) The weight of the protein released into the model gastric fluid is the model gastric fluid (sample) obtained by performing the above-mentioned treatments (4) and (5) on a 42 mesh screen (opening: 0.35 mm). ) And the concentration of the solution passed through was measured. At this time, a sample was prepared for each measurement condition. That is, in the graph described later, the time-dependent change of the sample under the same condition is shown instead of the time-dependent change of the same sample.

Experimental conditions were set by combining each enteral nutrient (concentration of agar, carrageenan, Tromake (registered trademark), etc.) and the type of model gastric fluid (pH = 2 and pH = 7). These experimental conditions are shown in Table 2. And the elution rate in each experimental condition was shown in FIGS.

FIG. 1 shows the results of agar (comparative control), FIG. 2 shows the results of carrageenan, and FIG. 3 shows the results of Tromake (registered trademark) (xanthan gum). At this time, the properties of the matrix were as follows: agar with high strength in agar, gel with low strength in carrageenan, and fluid sol in Tromake (registered trademark) (xanthan gum).

  In FIG. 1 (agar) for comparison, the matrix breaks and becomes brittle immediately after the matrix is pushed out of the syringe. The liquid food (nutrient component) is not held in the matrix immediately after the matrix is pushed out of the syringe. Since it is not held in the matrix, the portion (aqueous solution) is considered to easily cause gastroesophageal reflux. At this time, if the agar is used at a high concentration, the matrix is hard to break and is in a strong state, but a strong force is required to push the matrix out of the syringe. When the matrix is difficult to be pushed out from the syringe, the fluidity in the tube is deteriorated in the tube feeding method (eg, gastric administration method), and the physical properties are not suitable for the tube feeding method.

  In FIG. 2 (carrageenan), when the matrix is extruded from the syringe, the matrix is in an elongated state (string shape) while being pushed out of the syringe.

  In FIG. 3 (Tromake (registered trademark)), the overall tendency is similar to that in FIG. 2 (carrageenan). This elongated state (string shape) is broken by the light agitation shown in (4) above.

  Furthermore, it is confirmed in Example 2 that the gel-like (tromi-like) enteral nutrient is sufficiently broken and digested and absorbed by the body such as peristalsis of the stomach and intestinal tract.

  On the other hand, this elongate state (string shape) is retained when left standing, and the liquid food (nutrient component) is moderately retained in the matrix. It is thought that gastroesophageal reflux is unlikely to occur because it is moderately retained in the matrix. It is also useful for controlling the rate of digestion and absorption in tube feeding methods (such as transgastric administration).

  At this time, when carrageenan is used, a strong force is not required when the matrix is pushed out of the syringe. When the matrix is easily pushed out of the syringe, fluidity in the tube is improved in tube feeding methods (eg, gastric administration method), and physical properties suitable for tube feeding methods are obtained.

  In FIG. 3 (Tromake (registered trademark)), compared to FIG. 2 (carrageenan), there is resistance to physical operations such as stirring, and the liquid food (nutrient component) is easily held in the matrix. FIG. 2 (carrageenan) and FIG. 3 (Tromake (registered trademark)) showed somewhat different physical properties.

Elution rate of nutritional components from gel-like enteral nutrients in simulated gastric fluid within the stomach Under the experimental conditions assuming movements of the stomach and intestinal tract, etc., the elution rate of proteins from gel-like enteral nutrients The impact was examined. Experimental conditions are basically the same as in Example 1.

  Differences in specific experimental conditions between Example 1 and Example 2 are as follows.

  When a gel enteral nutrient was added to and held in the model gastric solution, it was allowed to stand in Example 1, whereas in Example 2, it was held with shaking. At this time, the shaking condition was 120 times / minute with an amplitude of about 35 mm. In Example 1, the temperature was 25 ° C. (normal temperature), whereas in Example 2, the temperature was 37 ° C.

In the same manner as in Example 1, the experimental conditions were determined by combining each enteral nutrient (concentration of agar, carrageenan, tromake (registered trademark), etc.) and model gastric juice (pH = 2 and pH = 7). Set. These experimental conditions are shown in Table 3. And the elution rate in each experimental condition was shown in FIGS.

FIG. 4 shows the experimental results of agar (comparative control), FIG. 5 shows the results of carrageenan, and FIG. 6 shows the results of Tromake (registered trademark) (xanthan gum).

  As the properties of the matrix, agar was a high-strength and brittle gel, carrageenan was a low-strength gel, and Tromake (registered trademark) (xanthan gum) was a fluid sol.

  When the pH was 7 (neutral), the protein was eluted with the passage of time in any of FIGS. Therefore, when a drug that suppresses the secretion of gastric acid (antacid) is used, the gel-like (tromi-like) enteral nutrient is sufficiently broken by gastric peristalsis and is digested and absorbed by the body. It is confirmed that it is done.

  On the other hand, when the pH was 2 (acidic), the behavior was different in FIGS.

  In FIG. 4 (agar), the protein was eluted immediately after the matrix was pushed out of the syringe, but hardly eluted as time passed thereafter. This is maintained under acidic conditions at a temperature of 37 ° C., so that enteral nutrient (part of the protein is denatured and insolubilized) and agar (finely crushed) are integrated into insoluble matter. By forming. Further, due to the further shaking operation, these insoluble materials aggregated and did not pass through the 42 mesh screen. These were confirmed visually. When the inside of a normal stomach was simulated, the high-strength and brittle gel-like enteral nutrient tended to form insoluble aggregates by operations such as gastric peristalsis.

  In FIG. 5 (carrageenan), the protein was not eluted immediately after the matrix was pushed out of the syringe, but gradually eluted with the passage of time thereafter. When the inside of a normal stomach was simulated, the low-strength gel-like enteral nutrient gradually broke down due to movements such as gastric peristalsis. This is thought to be because carrageenan was insolubilized under acidic conditions, forming a much stronger matrix than the neutral range. Based on these results, it is considered that the phenomenon that a low-strength gel-like enteral nutrient is gradually digested and absorbed in the body can be proved by a simulated experiment.

  In FIG. 6 (Tromake (registered trademark)), the protein was not eluted immediately after the matrix was pushed out of the syringe, but it was appropriately eluted with the passage of time thereafter. When the inside of a normal stomach was simulated, the fluid sol-type enteral nutrient broke moderately due to operations such as gastric peristalsis. This is thought to be due to the fact that Tromake (registered trademark) (xanthan gum) formed a stronger matrix than the neutral region under the acidic conditions, like carrageenan.

  However, carrageenan was insolubilized under acidic conditions, whereas xanthan gum was not insolubilized under acidic conditions. Therefore, there is no formation of aggregates and the like, and it is considered that nutrient components are appropriately eluted from the matrix.

  Based on these findings, it is considered that the phenomenon that the fluid sol enteral nutrient is digested and absorbed into the body can be proved by a simulated experiment.

  In Fig. 6 (Tromake (registered trademark)), compared to Fig. 5 (carrageenan), it is fragile due to physical movements assuming the peristalsis of the stomach and intestinal tract, etc., and the liquid food (nutrients) is released appropriately from the matrix. Easy to be. FIG. 5 (carrageenan) and FIG. 6 (Tromake (registered trademark)) showed different physical properties.

  From Example 1, the gel-like enteral nutrient of the present invention is as follows: “Gel-like enteral nutrient and an aqueous solution having a temperature of 25 ° C. are mixed at a weight ratio of 3: 7, and gently for 5 seconds. In the case of stirring, a numerical value (dissolution rate) obtained by dividing the weight of the protein eluted from the gel enteral nutrient into the aqueous solution by the weight of the protein contained in the gel enteral nutrient before mixing. ) Is 0 to 0.2 ". “The gel-like enteral nutrient and the aqueous solution having a temperature of 25 ° C. were mixed at a weight ratio of 3: 7, and the temperature was kept at 25 ° C. for 30 minutes, and then gently stirred for 5 seconds. In this case, a numerical value (elution rate) obtained by dividing the weight of the protein eluted from the gel enteral nutrient in the aqueous solution by the weight of the protein contained in the gel enteral nutrient before mixing is obtained. 0 to 0.45 ".

  As a result of the examination in Example 2, even if the peristaltic movement of the stomach or intestine is assumed for the gel-like enteral nutrient of the present invention that has been confirmed as in Example 1 described above, In a simulated experiment, we were able to prove the phenomenon that the body gradually digested and absorbed.

  It is possible to provide an enteral nutrient that can be safely and easily ingested by a person with difficulty in swallowing or a patient undergoing tube administration without causing gastroesophageal reflux and a method for preparing the same. And the gel-like enteral nutrient which can control appropriately the physical property and state of the enteral nutrient in the stomach in a tube feeding method etc., and its preparation method can be provided.

It is the graph which showed the time-dependent change of the elution rate of the enteral nutrient of a comparison control at the time of hold | maintaining in a stationary state using agar for a trotomy regulator. It is the graph which showed the time-dependent change of the elution rate of the enteral nutrient in the case of hold | maintaining in a stationary state using carrageenan as a trotomy regulator. It is the graph which showed the time-dependent change of the elution rate of the enteral-nutrient at the time of hold | maintaining in a stationary state using Tromake (trademark) as a trolley adjusting agent. It is the graph which showed the time-dependent change of the elution rate of the enteral nutrient of a comparison control at the time of hold | maintaining in a shaking state using agar for a trotomy regulator. It is the graph which showed the time-dependent change of the elution rate of the enteral nutrient in the case of hold | maintaining in a shaking state using a carrageenan as a trolley adjusting agent. It is the graph which showed the time-dependent change of the elution rate of the enteral-nutrient at the time of hold | maintaining in a shaking state using Tromake (trademark) as a trolley adjusting agent.

Claims (4)

When the gel-like enteral nutrient extruded from the syringe and the aqueous solution having a pH of 2 to 7 and a temperature of 25 ° C. are mixed at a weight ratio of 3: 7, immediately after stirring gently for 5 seconds, the aqueous solution is mixed with the aqueous solution. the weight of the protein eluted from the gel-like enteral nutrient, a value obtained by dividing the weight of the gel of the proteins contained in the enteral nutrient before mixing (dissolution rate) is 0 to 0.2 like,
By adding carrageenan at 0.1 to 3% by weight and / or xanthan gum at 0.2 to 2% by weight with respect to the total amount of the gel enteral nutrient, the viscosity of the gel enteral nutrient is adjusted. A method of preparing a gel enteral nutrient by adjusting to 100 to 50,000 cP . The gel-like enteral nutrient extruded from the syringe and an aqueous solution having a pH of 2 to 7 and a temperature of 25 ° C. were mixed at a weight ratio of 3: 7, and the temperature was kept at 25 ° C. for 30 minutes and then 5 A numerical value obtained by dividing the weight of the protein eluted from the gel-like enteral nutrient in the aqueous solution by the weight of the protein contained in the gel-like enteral nutrient before mixing when gently stirring for 2 seconds. (Elution rate) to be 0 to 0.45 ,
By adding carrageenan at 0.1 to 3% by weight and / or xanthan gum at 0.2 to 2% by weight with respect to the total amount of the gel enteral nutrient, the viscosity of the gel enteral nutrient is adjusted. A method of preparing a gel enteral nutrient by adjusting to 100 to 50,000 cP . When the gel-like enteral nutrient extruded from a syringe and an aqueous solution having a pH of 2 to 7 and a temperature of 25 ° C. are mixed at a weight ratio of 3: 7, immediately after stirring gently for 5 seconds, the aqueous solution The value (elution rate) obtained by dividing the weight of the protein eluted from the gel enteral nutrient by the weight of the protein contained in the gel enteral nutrient before mixing is 0 to 0.2. like,
By adding carrageenan at 0.1 to 3% by weight and / or xanthan gum at 0.2 to 2% by weight with respect to the total amount of the gel enteral nutrient, the viscosity of the gel enteral nutrient is adjusted. Adjust to 100-50,000 cP
A method for preparing a gel enteral nutrient for use in tube feeding . A gel-like enteral nutrient extruded from a syringe and an aqueous solution having a pH of 2 to 7 and a temperature of 25 ° C. are mixed at a weight ratio of 3: 7, and then kept at a temperature of 25 ° C. for 30 minutes. A numerical value obtained by dividing the weight of the protein eluted from the gel-like enteral nutrient in the aqueous solution by the weight of the protein contained in the gel-like enteral nutrient before mixing when gently stirring for 2 seconds. (Elution rate) to be 0 to 0.45,
By adding carrageenan at 0.1 to 3% by weight and / or xanthan gum at 0.2 to 2% by weight with respect to the total amount of the gel enteral nutrient, the viscosity of the gel enteral nutrient is adjusted. Adjust to 100-50,000 cP
A method for preparing a gel enteral nutrient for use in tube feeding .

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