Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
  • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
  • A23L29/206—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
  • A23L29/231—Pectin; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/08—Solutions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/02—Nutrients, e.g. vitamins, minerals
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
  • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

• the present invention relates to an aqueous pectin solution useful as a thickener for enteral nutrients.
• Tube feeding is being used to provide nutrition to those who cannot or cannot take food and beverages orally.
• enteral nutrients are liquids with viscosity that can be administered by tube, so enteral nutrients administered into the stomach may flow back into the esophagus and cause vomiting or rapidly enter the intestines. It causes problems such as causing diarrhea and damping syndrome.
• the enteral nutrient is adjusted to have a low viscosity so that it passes through a thin tube, so that reflux into the esophagus, diarrhea, and dumping syndrome are problematic.
• Low methoxyl pectin has a degree of esterification (DE), which is a ratio of methyl esterified galacturonic acid constituting pectin, of less than 50%, and forms a gel in the presence of divalent metal ions such as calcium ions.
• DE degree of esterification
• enteral nutrients having a larger amount particularly enteral nutrients having a sodium concentration of 180 mg / 100 mL or more are also used.
• enteral nutrients with a high sodium content have a problem that conventional low methoxyl pectin does not thicken.
• increasing the content of low methoxyl pectin increases the viscosity of the aqueous solution of low methoxyl pectin, which increases the burden on medical personnel who inject using a syringe when passing through a thin tube such as a nasogastric tube It will be.
• the present invention can increase the viscosity even with enteral nutrients containing sodium at a high concentration of 180 mg / 100 mL or more, and is suitable for tube administration in a thin tube.
• An object of the present invention is to provide an aqueous pectin solution that does not generate starch during storage.
• the present invention has found that the above-mentioned object can be achieved when the degree of esterification and molecular weight of pectin used in a pectin aqueous solution are within a specific range and the calcium concentration contained in the pectin aqueous solution is below a specific range. Completed.
• the present invention relates to a pectin aqueous solution containing pectin having an esterification degree of 5 to 15% and a viscosity average molecular weight of 10,000 to 35000, wherein the calcium concentration of the pectin aqueous solution is 9 ppm or less, and the viscosity (25 ° C.) of the pectin aqueous solution is
• the viscosity (25 ° C.) of a mixed solution of 100 mL of the pectin aqueous solution and 200 mL of calcium / sodium aqueous solution of 0.019 mol / L calcium chloride and 0.020 mol / L sodium citrate is 700 to 10000 mPa ⁇ s.
• the present invention also provides a thickener for tube administration comprising the above-mentioned aqueous pectin solution.
• a pectin aqueous solution having a degree of esterification of 5 to 15% and a pectin content of 1 to 5% by mass was prepared by diluting the pectin with water.
• a method of adjusting the viscosity (25 ° C.) of a pectin aqueous solution to 1 to 30 mPa ⁇ s by diluting pectin whose calcium concentration of the pectin aqueous solution is 9 ppm or less with water is provided.
• aqueous pectin solution of the present invention not only conventional enteral nutrients with a sodium content of 150 mg / 100 mL or less, enteral nutrients with a higher sodium content, particularly enteral nutrition with a sodium content of 180 mg / 100 mL or more.
• the agent can also increase the viscosity, and prevent reflux of enteral nutrients administered into the stomach, diarrhea, and damping syndrome.
• aqueous pectin solution of the present invention since starch is not easily generated during storage, the user can use it with peace of mind.
• the aqueous pectin solution of the present invention contains low methoxyl pectin having a degree of esterification (DE) of 5 to 15% as a main component.
• DE degree of esterification
• the degree of esterification of pectin is as low as 15% or less and the calcium reactivity is high, so that the viscosity average molecular weight is adjusted to 10,000 to 35,000, preferably 12,000 to 27,000, and the pectin aqueous solution
• the enteral nutrient has a sodium content of 180 mg / 100 mL or more and a high sodium concentration, and the sodium content is lower than that, the enteral nutrient is By mixing with an aqueous pectin solution, the enteral nutrient can be thickened and reflux of enteral nutrients administered into the stomach, diarrhea, and dumping syndrome can be prevented.
• the viscosity of the mixed solution (25 ° C. ) (BH viscometer) can be 600 to 10000 mPa ⁇ s, preferably 800 to 3000 mPa ⁇ s.
• the degree of esterification of pectin is set to 5 to 15%, more preferably 6 to 13%. If the degree of esterification is higher than 15%, the reactivity of the aqueous pectin solution with calcium ions is low, and the enteral nutrient cannot be thickened sufficiently.
• the degree of esterification of the aqueous pectin solution can be measured by titration with an alkaline solution.
• the pectin mainly composed of the aqueous pectin solution of the present invention has a viscosity average molecular weight of 10,000 to 35,000, preferably 12,000 to 27,000.
• the viscosity average molecular weight is an average molecular weight calculated by an intrinsic viscosity method. If the viscosity average molecular weight of pectin is too large, a strong insoluble gel is generated by reaction with calcium ions, which is not preferable from the viewpoint of digestion and absorption. From the point of increasing the viscosity to an appropriate viscosity, the viscosity average molecular weight of the pectin aqueous solution is 35000 or less, preferably 27000 or less, more preferably 16000 or less.
• the viscosity average molecular weight is 10,000 or more, preferably 12,000 or more. More preferably, it is 14000 or more.
• the viscosity average molecular weight of pectin it becomes easy to adjust the viscosity of the aqueous pectin solution to 30 mPa ⁇ s (25 ° C.) or less suitable for tube administration.
• the pectin contained in the aqueous pectin solution of the present invention has an esterification degree of 5 to 15% and a viscosity average molecular weight of 10,000 to 35,000, preferably 12,000 to 27,000.
• the viscosity of the mixed solution is 30 mPa ⁇ s (25 ° C.) or less suitable for tube administration. Thicken to 600 mPa ⁇ s or more. Since the calcium ion concentration of the enteral nutrient is at least 10 ppm or more, the enteral nutrient can be thickened by the aqueous pectin solution of the present invention.
• Such thickening action of the aqueous pectin solution of the present invention is achieved by stirring 100 mL of the aqueous pectin solution of the present invention and 200 mL of an aqueous calcium / sodium solution of 0.019 mol / L calcium chloride and 0.020 mol / L trisodium citrate for 30 seconds.
• the viscosity (25 ° C.) 5 minutes after mixing the pectin aqueous solution and the calcium / sodium aqueous solution is measured at 20 rpm with a BH viscometer at a liquid temperature of 25 ° C., preferably 700 to 10000 mPa ⁇ s, preferably By being 1400 to 8000 mPa ⁇ s, it is distinguished from the conventional pectin aqueous solution.
• the calcium content and sodium content in this calcium / sodium aqueous solution are the calcium content and sodium content of general enteral nutrients, and when pectin aqueous solution is mixed with enteral nutrients Used to examine thickening effect.
• a conventional pectin aqueous solution is mixed with this calcium / sodium aqueous solution, the above viscosity range is not reached.
• the aqueous pectin solution of the present invention has a viscosity (25 ° C.) of 30 mPa ⁇ s or less, preferably 10 mPa ⁇ s or less. If the viscosity of the aqueous pectin solution is too high, it becomes difficult to administer the aqueous pectin solution through a tube having an inner diameter of about 1 to 5 mm that is used for tube administration.
• the aqueous solution is suitable for tube administration and can be preferably used particularly by nasogastric tube method.
• the viscosity (25 degreeC) of the pectin aqueous solution of this invention shall be 1 mPa * s or more from the point which increases an enteral nutrient moderately.
• the content of pectin can be appropriately adjusted according to the molecular weight of pectin so that the viscosity of the pectin aqueous solution is in the above range.
• the viscosity average molecular weight of pectin is 10,000 to 35000.
• the content may be 1 to 5% by mass. If the content of pectin is too small, the enteral nutrient cannot be thickened sufficiently. On the other hand, if it is too much, a strong gel is formed by the reaction with the enteral nutrient, so from the aspect of digestion and absorption. It is not preferable.
• the aqueous pectin solution of the present invention is also characterized by a low calcium concentration of 9 ppm or less. Since conventional low methoxyl pectin having a degree of esterification of about 10% contains 1000 ppm or more of calcium, even when low methoxyl pectin is diluted to a 1% by mass aqueous solution, the calcium concentration of the aqueous solution is 10 ppm or more. Become. When such a conventional low methoxyl pectin is made into an aqueous solution, starch is produced during storage for about 10 days at room temperature. For this reason, those who use it as a thickener for enteral nutrients are made to worry about quality.
• the tube may be blocked and the tube may be clogged.
• the generation of starch during storage of the aqueous pectin solution is suppressed by setting the calcium concentration in the aqueous pectin solution to 9 ppm or less, preferably 4.5 ppm or less.
• the aqueous pectin solution of the present invention has a pH of preferably 2 to 8, more preferably 3.5 to 6. This is because, when the pH is too low or too high, the pectin may have a low molecular weight during storage, and the viscosity average molecular weight of the pectin may fall below the above-described preferable range.
• the aqueous pectin solution of the present invention can contain optional components such as a pH adjuster, vitamins, minerals, thickening polysaccharides, and stabilizers as necessary.
• an aqueous pectin solution of the present invention for example, a commercially available low methoxyl pectin having a degree of esterification of 5 to 15% is used as a raw material pectin, and dissolved in pure water so that the pectin concentration is 1 to 5% by mass. An aqueous solution is prepared and its calcium concentration is measured.
• General pectin has a high calcium concentration, and when a pectin aqueous solution having a pectin concentration of 1 to 5% by mass is prepared, the calcium concentration of the aqueous pectin solution is 10 ppm or more.
• the pectin concentration of the pectin aqueous solution having a pectin concentration of 1 to 5% by mass exceeds 9 ppm
• the pectin concentration is similarly reduced to 1 to 5% by mass by subjecting the raw material pectin to a calcium reduction treatment.
• the calcium concentration in the prepared aqueous pectin solution is reduced to 9 ppm or less.
• the raw material pectin is selected as a pectin that can be used in the present invention without calcium reduction treatment.
• Pectin that has been subjected to calcium reduction treatment, or pectin selected as not requiring calcium reduction treatment is diluted with water and subjected to heat treatment or enzyme treatment as necessary to lower the molecular weight of pectin, resulting in a viscosity average molecular weight of 10,000.
• the aqueous pectin solution of the present invention can be obtained by adjusting the viscosity to 1 to 35000, preferably 12000 to 27000, so that the viscosity of the aqueous pectin solution is 1 to 30 mPa ⁇ s.
• you may perform a calcium reduction process after diluting pectin with water so that pectin aqueous solution may become the above-mentioned viscosity.
• water used here a pure water or ion-exchange water is preferable.
• examples of the calcium reduction treatment include a method of washing with a hydrous acidic solvent such as a nitric acid-containing isopropanol solution, a method of using an ion exchange resin, and a method of filtering through an ultrafiltration membrane.
• a hydrous acidic solvent such as a nitric acid-containing isopropanol solution
• a method of using an ion exchange resin and a method of filtering through an ultrafiltration membrane.
• the method using an ion exchange resin is preferable as a calcium reduction process from the point with few complexity of a manufacturing process.
• the molecular weight of the aqueous pectin solution it is preferable to reduce the molecular weight of the aqueous pectin solution to a viscosity average molecular weight of 10,000 to 35000 by performing heat and pressure treatment at a temperature of 100 to 145 ° C. for 2 to 100 minutes.
• This heat and pressure treatment may be performed after the pectin aqueous solution is filled in the container.
• the pH is adjusted by adding an organic acid such as phosphoric acid, acetic acid and citric acid, an organic acid salt such as acetate and citrate, and a pH adjusting agent such as phosphate. It is preferable to adjust to 2-8.
• the aqueous pectin solution of the present invention is useful as a thickener for tube administration that thickens enteral nutrients in the stomach. Can also be used.
• Example 1 pectin A having a degree of esterification of 7% was dissolved in pure water so as to be 3% by mass, 100 g of which was filled and sealed in a heat-resistant container, and heated and pressurized at a temperature of 110 ° C. for 30 minutes.
• the pectin aqueous solution was manufactured by processing.
• a pectin aqueous solution having a concentration shown in Table 1 was prepared using the raw material pectin A to G shown in Table 1, and the calcium reduction treatment or the pectin molecular weight reduction treatment was performed on the pectin aqueous solution as shown in Table 1.
• Pectin aqueous solutions of Examples 2 to 10 and Comparative Examples 1 to 8 were produced.
• Viscosity average molecular weight of pectin The viscosity average molecular weight was measured by the intrinsic viscosity method as follows. That is, a sample solution was prepared by diluting a pectin aqueous solution having a concentration shown in Table 1 with a 0.2 mol / L sodium chloride solution. Specifically, when the viscosity measured under conditions of BL type viscometer (manufactured by Toki Sangyo Co., Ltd.) rotor No. 10, 12 rpm, 25 ° C.
• the calcium content and sodium content of the enteral nutrient used are as follows.
• Janef K-4S Ca content 60 mg / 100 mL Na content: 180mg / 100mL
• Janef K-LEC Ca content 60 mg / 100 mL Na content: 80mg / 100mL
• the aqueous pectin solution of each example of the present invention has a pectin esterification degree in the range of 5 to 15% and a pectin viscosity average molecular weight in the range of 10,000 to 35,000. It can be seen that the aqueous solution is sufficiently thickened. In these examples, the molecular weight is reduced by heat and pressure treatment (Examples 1 to 8, 10) or by enzyme treatment (Example 9).
• Example 1 since the aqueous pectin solution of Example 1 was able to thicken both enteral nutrient (K-4S) rich in sodium and enteral nutrient (K-LEC) low in sodium, each example of the present invention It can be seen that enteral nutrients can be thickened regardless of whether the sodium content is high or low.
• the pectin used as a raw material is selected to have a low calcium content, so that the calcium concentration in the aqueous pectin solution is not reduced to 9 ppm or less (Example 1 7 and 9), which are obtained by reducing the calcium concentration by using an ion exchange resin so that the calcium concentration in the aqueous pectin solution is 9 ppm or less (Examples 8 and 10). Starch is not generated. In particular, when the calcium concentration in the aqueous pectin solution is 4.5 ppm or less (Examples 1 to 5, 7 to 9), it can be seen that no starch is generated.
• Comparative Example 1 having a viscosity average molecular weight exceeding 35000, a strong gel was formed by the reaction with the calcium / sodium aqueous solution, and the viscosity could not be measured. Therefore, when the aqueous pectin solution of Comparative Example 1 is mixed with an enteral nutrient in the stomach, a strong gel is formed in the stomach, digestion and absorption are not sufficiently performed, and the nutrition of the enteral nutrient cannot be absorbed in a necessary amount. Is considered to occur.
• the aqueous pectin solution of Comparative Example 5 has low reactivity with calcium / sodium aqueous solution due to the degree of esterification exceeding 15%, and contains not only enteral nutrient (K-4S) with high sodium content but also sodium content. A small amount of enteral nutrient (K-LEC) could not be thickened sufficiently.
• the pectin aqueous solutions of Comparative Examples 6, 7, and 8 were prepared from pectin having an esterification degree exceeding 15%.
• Comparative Example 6 the viscosity average molecular weight after the molecular weight reduction treatment exceeded 35,000, but due to the high degree of esterification, the calcium / sodium aqueous solution could not be sufficiently thickened.
• Comparative Example 7 since the molecular weight was not reduced by heat treatment, the calcium / sodium aqueous solution could be sufficiently thickened.
• the viscosity of the pectin aqueous solution itself exceeded 30 mPa ⁇ s, it was applied to the feeding tube. could not be injected.
• Comparative Example 2 the same pectin as in Example 1 was used as a raw material, but by increasing its content, the viscosity of the pectin aqueous solution itself exceeded 30 mPa ⁇ s, which could be injected into the feeding tube. There wasn't.
• Comparative Examples 2 to 4 and 6 to 9 in which the calcium concentration in the aqueous solution exceeded 9 ppm starch was generated after storage.
• Comparative Examples 2 and 3 were made from the same pectin as in Example 1, but in Comparative Example 2, the calcium concentration in the pectin aqueous solution increased due to the increased content of the raw pectin,
• Comparative Example 3 since the tap water was used as the dilution water, the calcium concentration in the aqueous pectin solution was increased by the calcium contained in the tap water, and it was considered that starch was generated respectively. It can be seen that the calcium concentration of the commercially available enteral nutrient thickening pectin solution of Comparative Example 9 is 10 times higher than that of Examples 1-10.
• the aqueous pectin solution of the present invention can be used as a thickener for enteral nutrients, a trotomy agent as a swallowing supplement, or a semi-solidifying agent.

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