JP2006249014A - Therapeutic agent for gastroesophageal reflux disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a therapeutic agent for gastroesophageal reflux disease which can safely be used. <P>SOLUTION: The therapeutic agent for gastroesophageal reflux disease is composed of a composition containing 2-8 w/v% protein and 0.3-3 w/v% dietary fiber. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a therapeutic agent for gastroesophageal reflux disease.

In severely mentally and physically handicapped children / persons, gastroesophageal reflux disease (GERD) causes complications such as reflux esophagitis, esophageal stenosis, vomiting, vomiting, poor weight gain, aspiration pneumonia, and tension. As treatment, devices such as posture, frequent administration of small amounts of tube-feeding nutrients, promotion of defecation / exhaust gas, pharmacotherapy, etc. have been carried out (Non-patent Documents 1 and 2). As this treatment method, thickened milk with increased milk viscosity is only used as a treatment for GERD in the West.
Pediatrics 33: 1229-1233, 2001 The Japanese Journal of Pediatrics 98: 193-198 (1984)

  An object of the present invention is to provide a therapeutic agent for gastroesophageal reflux disease that can be used safely.

  Therefore, the present inventor considered variously the pH change and the viscosity change of the composition combining the protein and the dietary fiber in consideration of safety, and as a result, the content of the protein and the dietary fiber was within a certain range. In this case, the viscosity before administration is low, and despite the ease of administration, the viscosity increases rapidly under low pH conditions in the stomach after administration, so that it does not cause gastroesophageal reflux disease, The present invention has been completed.

  That is, the present invention provides a therapeutic agent for gastroesophageal reflux disease comprising a composition containing 2 to 8% w / v protein and 0.3 to 3.0% w / v dietary fiber.

  The therapeutic agent for gastroesophageal reflux disease of the present invention has a low viscosity before administration, and is easy to administer normal trans- and tube administration, and the viscosity rapidly increases in the stomach after administration. No backflow occurs and safety is high. Therefore, it can be applied to a wide range of patients from elderly people to infants.

  The protein concentration in the composition used in the present invention is 2 to 8 w / v% from the viewpoint of rapidly increasing the viscosity in the stomach, but is further 2.25 to 8 w / v%, particularly 2.5 to 8 w / v. v% is preferred. When the protein concentration is less than 2 w / v%, a sufficient effect of increasing the viscosity in the stomach cannot be obtained. Here, the protein may be any of vegetable protein and animal protein, or both may be used in combination. Examples of plant proteins include soy protein, isolated soy protein, corn protein, and wheat protein. Examples of animal proteins include casein, whey protein, collagen, gelatin, egg protein and the like. The protein amount can be measured by the Kjeldahl method.

  The dietary fiber concentration in the composition of the present invention is 0.3 to 3 w / v% from the viewpoint of rapidly increasing the viscosity in the stomach, but is further 0.35 to 3 w / v%, particularly 0.5. ~ 3 w / v% is preferred. When the dietary fiber concentration is less than 0.3 w / v%, a sufficient effect of increasing the viscosity in the stomach cannot be obtained. As a dietary fiber source, soybean bran, pectin, guar gum or its enzymatic degradation product, glucomannan, seaweed, cellulose, hemicellulose, lignin, wheat bran and the like are used. The amount of dietary fiber in the composition of the present invention is a value determined based on the amount of dietary fiber measured by the enzyme-weight method in the dietary fiber source.

  The composition of the present invention preferably contains starch, particularly corn starch, from the viewpoint of the effect of increasing the viscosity in the stomach. The starch content is preferably 0.1 to 20 w / v%, more preferably 0.2 to 10 w / v%, and particularly preferably 0.25 to 5 w / v%.

  The composition of the present invention can further contain other nutrient sources. Such nutrient sources include carbohydrates (excluding dietary fiber), lipids, minerals and vitamins. Here, polysaccharides other than the above-mentioned dietary fiber and starch, oligosaccharides and monosaccharides are used as carbohydrates. As the polysaccharide, dextrin or the like is used, as the oligosaccharide, sucrose, maltose, lactose or the like is used, and as the monosaccharide, glucose, fructose, galactose or the like is used. As the polysaccharide, it is particularly preferable to use dextrin and pectin. The carbohydrate concentration in the composition of the present invention is preferably 1 to 40 w / v%, more preferably 5 to 30 w / v%.

  Examples of lipids include soybean oil, perilla oil, palm oil, corn oil, rapeseed oil, sunflower oil, fish oil, medium chain fatty acid triglyceride, olive oil and the like. The lipid concentration is preferably 0.5 to 20 w / v%, more preferably 1 to 10 w / v%. The lipid concentration can be measured by a chloroform / methanol mixed liquid extraction method.

  Examples of the mineral include sodium, potassium, calcium, magnesium, iron, zinc, chlorine, phosphorus, copper, manganese, selenium, chromium and the like. These minerals are preferably contained in a total of 0.01 to 10 w / v%, more preferably 0.1 to 5 w / v%. These minerals are preferably blended as inorganic acid or organic acid salts.

  As vitamins, vitamin A, thiamine, pyridoxine, ascorbic acid, tocopherol, nicotinamide, folic acid, pantothenic acid, cyanocobalamin, biotin, vitamin D, vitamin K, and salts thereof are used. These vitamins are preferably contained in a total of 0.01 to 5 w / v%, more preferably 0.5 to 3 w / v%.

  The therapeutic agent for gastroesophageal reflux disease of the present invention may further contain water, a buffer (pH adjusting agent), a fragrance and the like. The viscosity of the obtained composition is preferably 5 to 60 mPa · s at 25 ° C. The pH is preferably 4-8.

  The therapeutic agent for gastroesophageal reflux disease of the present invention has a low viscosity before administration of 5 to 60 mPa · s, preferably 10 to 30 mPa · s, and can be administered through the tube or tube. Since it raises to 900-3000 mPa * s, the backflow of the content from a stomach is prevented effectively.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in detail, this invention is not restrict | limited at all to this.

Example 1
The relationship between pH change and viscosity of a mixed solution of protein, dietary fiber and water was examined. Protein, dietary fiber (soybean bran), corn starch and purified water were added in the amounts shown in Table 1, and formulation No. 1 was added. 1-No. 24 solutions were prepared. The prescription No. 1-No. The viscosity of 24 when pH was not adjusted and the viscosity after adjusting the pH to about 2 with hydrochloric acid were measured. Table 2 shows the relationship between the prescription number and concentration and the results.

  As can be seen from Table 2, when the protein concentration is 2.6 w / v% or more and the dietary fiber concentration is 0.7 w / v% or more, the viscosity increases remarkably when the pH decreases. From this, it can be seen that the composition of the present invention rapidly increases in viscosity in the stomach and effectively prevents backflow of stomach contents.

Example 2
A composition A having the composition shown in Table 3 was prepared.

  The obtained composition A (agent A) and commercially available enteral nutrient B containing protein but no dietary fiber (agent B: protein 0.0438 w / v%, dietary fiber 0 w / v%) and C (C agent: protein 0.0352 w / v%, dietary fiber 0 w / v%), the change in viscosity at pH was examined. In addition, the composition was administered to rats fasted for 2 days, and the stomach contents were collected after a certain period of time and the viscosity and pH were measured.

A. Object and Method (1) Relationship between pH and Viscosity Using a B-type viscometer (Tokimec Co., Ltd.), 500 mL enteral nutrients heated to 37 ° C. to have a pH of 2, 4, 6 Hydrochloric acid was added to and the viscosity was measured. In addition, assuming the stomach, 500 mL of the composition was adjusted to pH 2.5 with hydrochloric acid, and the viscosity was measured over time.

(2) Viscosity and pH of stomach contents using rats
i) Experimental animals SD male rats fasted for 2 days were used. A sample of 1.0 mL / 100 g body weight was administered. In each group, the stomach was removed 10 and 20 minutes after administration, and the pH and viscosity of the collected stomach contents were measured.

ii) Viscosity measurement The viscometer was measured using a rotary E-type viscometer (Tokimec Co., Ltd.) at a measurement temperature of 37 ° C.

B. Results (1) Relationship between pH and Viscosity Table 4 shows the results of viscosity measurement according to the difference in pH, and Table 5 and FIG. In the viscosity measurement based on the difference in pH, the viscosity when pH was not adjusted (about pH 6.5) was 29 mPa · s for Agent A, and 6 and 5 mPa · s for Agent B and Agent C, respectively. With agent A, the viscosity increased under acidic conditions of 130 mPa · s at pH 6, 1959 mPa · s at pH 4, 2951 mPa · s at pH 2, and was strongly observed at low pH. In contrast, the B agent and the C agent showed an increase in viscosity of 920 and 587 mPa · s at pH 2, respectively, but the A agent showed a significant increase in viscosity with respect to the B and C agents.

  The change with time in viscosity at pH 2.5 was 29 mPa · s for agent A and 6 and 5 mPa · s for agent B and C when pH was not adjusted. After 5 minutes, the viscosity of Agent A increased to 2380 mPa · s, whereas that of Agent B and Agent C increased in viscosity to 803 and 532 mPa · s, respectively. , A agent significantly increased viscosity compared to B agent and C agent.

(2) Viscosity and pH of stomach contents using rats
The viscosity and pH of stomach contents using rats are shown in Table 6, and the viscosity is shown in FIG. The viscosity of the stomach contents 10 minutes after administration was 1855 mPa · s (1.6 times that of Agent B and 2.6 times that of Agent C) in the Agent A administration group. The viscosity of the agent A administration group was significantly higher than that of the agent C administration group. The viscosity 20 minutes after administration was 2155 mPa · s (1.7 times that of Agent B and 3.3 times that of Agent C) in the Agent A administration group. The agent A administration group showed significantly higher viscosity than the agent B administration group and the agent C administration group.
The pH of group A, B and C of the stomach contents was about 5 after 10 and 20 minutes, respectively.
The agent A which is the composition of the present invention rapidly increases in viscosity in the stomach and is found to be useful as a therapeutic agent for gastroesophageal reflux disease.

The change with time of viscosity at pH 2.5 is shown. 2 shows the viscosity of stomach contents using rats.

Claims (2)

  A therapeutic agent for gastroesophageal reflux disease comprising a composition containing 2 to 8 w / v protein and 0.3 to 3.0 w / v dietary fiber.   The therapeutic agent for gastroesophageal reflux disease according to claim 1, further comprising corn starch.

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