JP2023015409A - Oral gelatinous composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral gelatinous composition that stably comprises vitamin B₁ and has a stable gelatinous form.

SOLUTION: An oral gelatinous composition contains vitamin B₁, and a thickening agent with a jelly strength of 700-1500 g/cm², the composition having a pH of 2.8-3.8.

SELECTED DRAWING: None

COPYRIGHT: (C)2023,JPO&INPIT

Description

TECHNICAL FIELD The present invention relates to an oral gel composition containing vitamin _B1 .

Vitamin B1 is known to have various usefulness to the living body, and is widely used in orally ingested pharmaceuticals, quasi _- drugs, foods, and the like.
Forms such as tablets and beverages are mainly suitably used as forms that allow vitamin _B1 to be taken in sufficient amounts. are increasingly being adopted as
In the background of the adoption of such gel formulations, forms that are easy to administer or ingest and swallow are preferred by consumers, especially in relation to the increase in dysphagia accompanying the increase in the elderly population in developed countries. It is thought that there are reasons for this, such as the fact that it is easy to take in a short period of time and that the form that can reduce hunger is preferred.

Oral jelly containing 0.01 to 0.5% by weight of vitamin _B1 and 0.5 to 30% by weight of chondroitin sulfate as a known technology close to oral gel preparations containing vitamin _B1 (Patent Document 1), but the oral jelly is a non-flowing molded gel-like preparation, not a liquid or fluid viscous gel-like preparation.

Japanese Unexamined Patent Application Publication No. 2011-231051

According to the studies of the present inventors, an oral gel composition stably containing vitamin _B1 (the term "gel composition" in this specification means not a solid gel composition but a fluid It is difficult to realize a certain viscous liquid composition) and to realize an oral gel composition containing vitamin B _1s in a stable gel form, stably containing vitamin B _1s , Moreover, it is even more difficult to realize an oral gel composition with a stable gel form.

Accordingly, it is an object of the present invention to provide an oral gel composition that stably contains vitamin _B1 and has a stable gel form.

As a result of intensive studies, the present inventors have found that it contains vitamin _B1 and a thickening agent with a jelly strength in the range of 700 to 1500 g/cm ² and a pH in the range of 2.8 to 3.8. The inventors have found that the above-described problems can be solved by the oral gel composition, and have completed the present invention.

That is, the present invention includes the following aspects.
[1] An oral gel composition containing vitamin _B1 and a thickening agent having a jelly strength in the range of 700 to 1500 g/cm ² and a pH in the range of 2.8 to 3.8.
[2] Vitamin B ₁ type is thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate, dicetiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octotiamine, sicotiamine, bisive The oral gel composition according to [1] above, which is at least one selected from the group consisting of thiamine, bisbentiamine, prosultiamine, and benfotiamine.
[3] The oral gel composition according to [1] or [2] above, wherein the thickening agent is agar.
[4] The oral gel composition according to [3] above, wherein the reducing sugar content of the agar is 0.02% by weight to 0.05% by weight.
[5] The oral gel composition according to any one of [1] to [4] above, which has a hardness in the range of 0.08 to 0.35N.
[6] The oral gel composition according to any one of [1] to [5] above, which is used as a drug or quasi-drug.
[7] The oral gel composition according to any one of [1] to [6] above, which is packaged in a pouch-type container.

ADVANTAGE OF THE INVENTION According to this invention, the oral gel composition which contains vitamin _B1 class stably and whose gel form is also stable is provided.

Terms In the present specification, the term "gel composition" means a fluid and viscous liquid composition to distinguish it from a solid gel composition.
As used herein, the term "viscosifier" is a general term for additives mixed in to increase the viscosity of a liquid, as is commonly understood by those skilled in the art, and is an aqueous liquid (e.g., water, aqueous solution, aqueous dispersion). Means a substance that dissolves or disperses in to increase the viscosity (viscosity) of the aqueous liquid.

As used herein, the term "jelly strength" refers to a property of a thickening agent, according to the art convention for agar. As a reminder, the term is used in distinction from the term "gel strength," which describes one property of gels. As used herein, the "jelly strength" of a thickening agent is common regardless of the type of thickening agent used in the present invention, and is commonly determined by the measurement method described in JIS K 8263: 2015 for agar. strength. That is, the "jelly strength" of a thickening agent is the strength of a gel prepared by dissolving the thickening agent in water at a concentration of 1.5 wt%. Here, purified water is used as water.

The symbols and abbreviations in this specification are understood to have meanings commonly used in the technical field to which the present invention belongs, unless otherwise specified.
Unless otherwise specified, any step, treatment or operation described herein is performed at room temperature. As used herein, room temperature means a temperature within the range of 10-35°C.

Oral Gel Composition The oral gel composition of the present invention contains vitamin _B1 and a thickening agent having a jelly strength within the range of 700 to 1500 g/cm ² .
Components contained in the oral gel composition of the present invention and components that may be contained are described below.

・Vitamin B ₁ type
Examples of vitamin _B1s used in the present invention are thiamine, bisthiamine, thiamine disulfide, dicetiamine, fursultiamine, octotiamine, sicotiamine, bisivetiamine, bisbentiamine, prosultiamine, and benfotiamine, and their salts, solvates (eg hydrates), and solvates (eg hydrates) of salts. Examples of such salts include hydrochloride, nitrate, and cetyl sulfate.

The vitamin _B1 is preferably thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate, disetiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octotiamine, sicotiamine, bis It can be one or more selected from the group consisting of ibtiamine, bisbentiamine, prosultiamine, and benfotiamine.
_A vitamin B1 group particularly suitably used in the present invention is fursultiamine or its hydrochloride.

The amount of vitamin _B1 in the oral gel composition of the present invention is about 0.00005 to 0.5 w/v%, preferably about 0.0002 to 0.25 w/v%, based on the total composition. , more preferably about 0.0005 to 0.05 w/v%, more preferably about 0.001 to 0.03 w/v%.

・Active ingredients other than vitamin _B1
In the oral gel composition of the present invention, pharmaceuticals and pharmaceuticals including active ingredients other than vitamin _B1 , such as vitamins other than vitamin _B1 , amino acids, etc., as long as they do not inhibit the effects of the present invention Others used in quasi-products, foods with health claims (e.g., foods with function claims, foods with nutrient function claims, foods for specified health uses), or general foods (e.g., nutritional supplements, health supplements, nutritionally balanced foods), etc. It may further contain one or more active ingredients.

Examples of vitamins other than vitamin _B1 are vitamin A (e.g., retinol, retinoic acid, retinal, retinol acetate, retinol palmitate, vitamin _A oil, cod liver oil, strong cod liver oil), vitamin B2 [ Examples: riboflavin, riboflavin derivatives (e.g. riboflavin esters such as riboflavin phosphate, riboflavin acetate, riboflavin butyrate; flavin adenine dinucleotide sodium, etc.) and salts thereof (e.g. riboflavin sodium phosphate)], vitamin _B6 class [e.g. pyridoxine, pyridoxamine, pyridoxal, their derivatives (e.g. pyridoxine phosphate, pyridoxal phosphate hydrate, pyridoxamine phosphate, pyridoxine palmitate) and their salts (e.g. pyridoxine hydrochloride , pyridoxal hydrochloride, pyridoxamine dihydrochloride)], vitamin _B12 group (e.g. cobalamin, cyanocobalamin, methylcobalamin, adenosylcobalamin, hydroxocobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate), vitamin C group (e.g.: Ascorbic acid, magnesium ascorbate phosphate, sodium ascorbate, calcium ascorbate, tocopheryl acetate ascorbate), vitamin Ds (e.g. ergocalciferol, cholecalciferol), vitamins E (e.g. d-succinate) α-Tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, d-α-tocopherol calcium succinate, calcium tocopherol succinate, d-α-tocopherol acetate, dl-α-tocopherol acetate, d -α-tocopherol, dl-α-tocopherol), niacins (e.g. nicotinic acid, nicotinamide), pantothenic acids (e.g. panthenol, calcium pantothenate, sodium pantothenate), and other vitamins (e.g. vitamin Ks, biotin, folic acid, gamma-oryzanol), and combinations thereof.

Examples of the amino acids include aspartic acid (e.g. L-aspartic acid, potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, potassium/magnesium aspartate equivalent mixture), glutamic acid (e.g. L -glutamic acid), arginine (e.g. L-arginine, L-arginine hydrochloride), tryptophan (e.g. L-tryptophan), lysine (e.g. L-lysine hydrochloride, L-lysine acetate), glycine, leucine (e.g. : L-leucine), isoleucine (e.g. L-isoleucine), threonine (e.g. L-threonine), cysteine (e.g. L-cysteine, L-cysteine hydrochloride, L-cysteine hydrochloride hydrate), valine (e.g. : L-valine), histidine (eg, L-histidine, L-histidine hydrochloride, L-histidine hydrochloride hydrate), and methionine (eg, DL-methionine), and combinations thereof.

Other examples of the other active ingredients include taurine (aminoethylsulfonic acid), ursodesoxycholic acid, carnitine chloride, orotic acid, choline orotate, gamma-oryzanol, calcium citrate, calcium glycerate, calcium gluconate, Diisopropylamine dichloroacetate, calcium carbonate, precipitated calcium carbonate, calcium lactate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, ferric ammonium citrate, ferrous fumarate, glucuronolactone, glucuronic acid, glucuronic acid amide, caffeine , anhydrous caffeine, sodium chondroitin sulfate, inositol, glycyrrhizic acid, sodium glycyrrhizinate, sodium gluconate, choline bitartrate, magnesium carbonate, thioctic acid, thioctic acid amide, dehydrocholic acid, pantethine, yoke lecithin, rutin, and crude drugs ( Examples: Asan yak, fennel, eleuthero, oleifera, processed daisan, guarana, licorice, Chinese wolfberry, cinnamon bark, red ginseng, saffron, hawthorn, sanyak, peony, syukusha, ginger, jotei, hawthorn, taisou, clove, chimp, radish, toshishi , Eucommia, Citrus, Carrot, Garlic, Bukuryo, Muirabuama, Mokkou, Yakuchi, Yokuinin, Longanniku, Rokujyo, Kaiba, Citrus, Bald Tentacle, Astragalus, Byakujutsu, Royal Jelly), and combinations thereof.

The amount of these active ingredients other than vitamin _B1 is appropriately set according to the type, purpose, and the like.

・Thickening agent
As a result of intensive studies, the present inventors found that when the jelly strength of the "viscosity agent" is _less than 700 g/cm ² , the acid resistance is poor. It was found that it leads to a significant increase in water separation and a decrease in hardness.
In addition, when the jelly strength of the "viscosity agent" exceeds 1500 g/cm ² , the use concentration (the amount of the viscosity agent in the gel composition) is reduced, so that the desired physical properties are not obtained, and the gel composition is also not produced. It was found that it leads to an increase in syneresis over time.
Therefore, the jelly strength of the “viscous agent” used in the oral gel composition of the present invention is within the range of 700-1500 g/cm ² , preferably within the range of 900-1200 g/cm ² , more preferably It ranges from 950 to 1150 g/cm ² .

The "viscosity agent" in the oral gel composition of the present invention is preferably "agar (including powdered agar powder)".
As used herein, agar is a polysaccharide obtained from one or more seaweeds selected from the group consisting of seaweeds belonging to the genus Agaricus, seaweeds belonging to the genus Gracilaria, and seaweeds belonging to the genus Magnolia.

Various agars can be suitably used in the present invention as long as they have a jelly strength within the range of 700 to 1500 g/cm ² .
Such agars are commercially available, and specific examples include agar powder PS-8
8 (product name, Ina Food Industry), agar powder T-1 (product name, Ina Food Industry), and the like.

Agar has a macromolecular structure in which galactose and anhydrogalactose are linked, and the sugar at the end of the molecule exists as a reducing sugar, exhibiting activity as a reducing sugar. A reducing sugar is a sugar that forms an aldehyde group or a ketone group in basic solution and is oxidized by an oxidizing agent to give aldonic acid or aldaric acid. Reducing sugars include, for example, all monosaccharides such as glucose, fructose and glyceraldehyde, and maltose-type disaccharides and oligosaccharides such as lactose, arabinose and maltose.
As a result of intensive studies by the present inventors, from the viewpoint of the stability of vitamin _B1 , it is desirable that the content of reducing sugars in agar is 0.02% by weight or more. From the viewpoint of preventing this, it has been found that the reducing sugar content of agar is desirably 0.05% by weight or less.
Therefore, the agar used in the present invention preferably has a reducing sugar content of 0.02% to 0.05% by weight.
The reducing sugar content in agar can be measured by a known method such as the Park-Johnson method (eg, Science of Carbohydrates (2), p. 368).

The content of the thickening agent in the oral gel composition of the present invention is preferably 0.008 to 85 w/w%, more preferably 0.03 to 40 w/w%, still more preferably 0.08 to 8 w/w%.

For the purpose of further increasing the viscosity of the oral gel composition of the present invention, xanthan gum (Ina Food Industry Co., Ltd., Ultraxanthan), guar gum (Ina Food Industry Co., Ltd., Guar Gum), etc. may be added in addition to the agar described above, if necessary. may contain.
The mass ratio of agar to xanthan gum and/or guar gum in the oral gel composition of the present invention is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 2 parts by mass, per 1 part by mass of agar. .

・Additional ingredients other than thickening agents
In the oral gel composition of the present invention, in addition to the above components, other components, such as components that can generally be added to oral gel compositions (e.g., sweetener , flavoring agents, preservatives, preservatives, flavoring agents, fragrances, cooling agents, surfactants, solubilizers, emulsifiers, solvents, pH adjusters, buffering agents, suspending agents, coloring agents, stabilizers , antifoaming agent, solubilizing agent, bitterness masking agent).

Examples of sweeteners include sugars (e.g. glucose, galactose, fructose, sucrose, lactose, maltose, isomerized sugar, liquid sugar, invert liquid sugar, trehalose), polysaccharides (e.g. oligosaccharides, starch), sugars Alcohols (e.g. erythritol, xylitol, maltitol, sorbitol, hydrogenated maltose starch syrup, powdered hydrogenated maltose starch syrup), high intensity sweeteners (e.g. acesulfame potassium) and non-sugar sweeteners (e.g. sucralose, stevia extract, saccharin, aspartame), and combinations thereof.
Examples of flavoring agents include acidulants such as citric acid or its hydrates, sodium citrate, malic acid (eg, DL-malic acid), and fruit juices, and combinations thereof.
Examples of preservatives or preservatives include benzoic acid, sodium benzoate, sodium sorbate, and parabens (eg, ethyl parahydroxybenzoate, butyl parahydroxybenzoate, propyl parahydroxybenzoate), and combinations thereof.
Examples of flavoring agents, fragrances or cooling agents are orange oil, menthol, vanillin and its derivatives (e.g. ethyl vanillin), and various flavors (e.g. strawberry flavor, cherry flavor, orange flavor, grapefruit flavor, apple flavor). , lemon flavor, grape flavor, coffee flavor, black tea flavor, bitter flavor, herbal mint flavor, chocolate flavor, spice flavor), and combinations thereof.
Examples of surfactants include sucrose fatty acid esters, propylene glycol, polyoxyethylene (160) polyoxypropylene (30) glycol (poloxamer 188), polyoxyethylene hydrogenated castor oils (e.g. polyoxyethylene hydrogenated castor oil 60 ), polysorbate 20, and polysorbate 80, and combinations thereof.
Examples of solubilizers include refined soybean lecithin, soybean lecithin, soybean oil, medium-chain triglycerides, macrogol 4000, macrogol 6000, liquid paraffin, sucrose fatty acid esters, polyoxyethylene hydrogenated castor oils, and polysorbate 80, as well as combinations thereof.
Examples of emulsifying agents include sucrose fatty acid esters, polyoxyethylene hydrogenated castor oils, polysorbate 20, polysorbate 80, refined soy lecithin, soy lecithin, medium chain triglycerides, and liquid paraffin, and combinations thereof.
Examples of solvents include water (eg, purified water), ethanol, propylene glycol, olive oil, sesame oil, castor oil, soybean oil, and liquid paraffin.
Examples of pH adjusters or buffers are phosphoric acid, lactic acid, acetic acid, carbonic acid and their salts, hydrochloric acid, sodium hydroxide, potassium hydroxide, citrate buffer (0.2M), and sodium bicarbonate, and includes combinations of
Examples of suspending agents include gum arabic, microcrystalline cellulose, veegum, xanthan gum, guar gum, gelatin, metolose and its salts, carmellose and its salts, and combinations thereof.
Examples of coloring agents include caramel, beta-carotene, and various food colorings (eg, Food Yellow No. 1, Food Red No. 2), and combinations thereof.
Examples of stabilizers include silicone resins, glycerin, salts of edetic acid, sodium chloride, and salts of pyrosulfite, and combinations thereof.
Examples of antifoam agents include silicone resins, silicone oils, ethanol, glycerin fatty acid esters, dimethylpolysiloxane, sucrose fatty acid esters, polyoxyl stearate, sosulbitan fatty acid esters, sorbitan trioleate, and polysorbate 80, and combinations thereof. contain.
Examples of solubilizing agents include propylene glycol, cyclodextrin, and arginine, and combinations thereof.
Examples of bitterness-masking agents include phosphatidyls [eg, BMI-60 (product name, Kao Corporation)].

The amount of additive components other than these thickening agents is appropriately set according to the type, purpose, and the like.

pH of oral gel composition
In order to provide an oral gel composition that stably contains vitamin _B1 (e.g., fursultiamine or its hydrochloride) and that stably retains the gel form, the present inventors We have found that the upper limit of the pH of the composition is 3.8 or less, more preferably 3.6 or less, and even more preferably 3.5 or less. Also, the inventors have found that the lower limit of the pH of the composition is 2.8 or higher, more preferably 3.1 or higher, and still more preferably 3.3 or higher.
That is, the pH of the oral gel composition of the present invention is within the range of 2.8 to 3.8, more preferably within the range of 3.1 to 3.6, and further preferably within the range of 3.3 to 3.5. Within range.

The pH may be adjusted, for example, by using a pH adjusting agent or buffer as described above.
In measuring the pH of the oral gel composition in the present invention, the composition is pulverized using a commercially available food mixer to make a homogeneous solution, and the pH is measured according to the general test method of the Japanese Pharmacopoeia. The test should be conducted in accordance with the law.

Form of oral gel composition It can be suitably used as a "gel-like preparation".
It is determined in light of common general technical knowledge that the formulation is not a solid formulation such as a gel, but a liquid or fluid viscous gel formulation.

The consistency of the gel composition can be indicated by the hardness of the gel composition, and it can be said that a gel composition having a high hardness has a high viscosity.
The oral gel composition of the present invention preferably has a hardness of, for example, 0.05 N or more, more preferably 0.08 N or more, and even more preferably 0.10 N or more, as measured by the test method described below. By having such hardness, the oral gel composition of the present invention can prevent aspiration and can be easily administered or ingested.
The hardness of the oral gel composition of the present invention is preferably 0.50N or less, more preferably 0.35N or less, still more preferably 0.30N or less. By having such hardness, the oral gel composition of the present invention is easy to administer or ingest.
The hardness of the oral gel composition of the present invention is preferably in the range of 0.05 to 0.50N, more preferably in the range of 0.08 to 0.35N, still more preferably 0.10 to 0.35N. .30N range.

The oral gel composition of the present invention is orally administered or orally ingested.
The oral gel composition of the present invention can be used as a drug, quasi-drug, food with health claims (e.g. food with functional claims, food with nutrient function claims, food for specified health use), or general food (e.g. dietary supplement, health supplement). food, nutritious food) and the like.

The oral gel composition of the present invention has high stability in its gel form.
In the present invention, the fact that the gel form has high stability means that, physically,
(1) Syneresis is suppressed even after storage under severe conditions (e.g., high temperature and / or long term), and / or (2) Harsh conditions (e.g., high temperature and / or It means that the decrease in hardness is suppressed even after storage for a long period of time.
Moreover, functionally, it means that the texture of the gel composition is maintained.

Here, the measurement of the amount of syneresis of the gel composition and the calculation of the syneresis rate are carried out by the following measuring methods.
<Method for measuring syneresis of gel composition>
In this measurement method, a mesh with an opening of 2 mm [Japanese Pharmacopoeia 17th Edition, Sieve No. 8.6 (2000 μm)] and a diameter of 200 mm is used as a sieve.
After placing the gel composition to be tested in a container and exposing it to predetermined storage conditions, the total amount of the contents of the container was placed on a sieve with a sieve underlay, the mass was measured, and the mass was A ( g). Next, after tilting the sieve at 45 degrees and holding it for 1 minute, the mass of the liquid (water syneresis) that fell from the sieve under the sieve was measured, and this was B (g). calculate.
Separation rate (%) = B (g) / A (g) x 100

In the oral gel composition of the present invention, the high stability of the gel form is due to the appropriate hardness of the gel composition even after storage under severe conditions (e.g., high temperature and/or long term). maintained.

The oral gel composition of the present invention preferably has a ratio of firmness when stored in a refrigerator (i.e. at about 4°C) for 8 weeks to firmness when stored at 50°C for the same period (herein In the book, this may be referred to as the "remaining rate of hardness".As understood from this definition, the residual rate of hardness may exceed 100%.), but is preferably 65% or more. , more preferably 70% or more, and still more preferably 80% or more.

The hardness of the oral gel composition of the present invention is measured by the following measurement method using the gel composition remaining on the sieve as a sample in the method for measuring syneresis of the gel composition. be done.
<Method for testing hardness of gel composition>
For this test, a material testing machine EZ-SX (product name, Shimadzu Corporation) capable of measuring the compressive stress of a substance by linear motion (load cell: 50 N, test jig: universal design hood test set, software: TRAPEZIUM X texture, constant temperature device: cold and hot constant temperature chamber), or equivalent.
The sample is filled into a container (diameter 40 mm, height 20 mm) to a height of 15 mm, and using the material testing machine, a resin circular plunger (diameter 20 mm, height 8 mm) is compressed at a compression rate of 10 mm / sec, and It is compressed twice under the condition of a clearance of 5 mm, and the compressive stress at that time is measured. Measurements are made at 20±2°C.
The maximum value of compressive stress in two compressions is taken as the hardness of the sample.

As a sample in the test, the gel composition remaining on the sieve by the method for measuring syneresis of the gel composition is used.
Therefore, if no gel composition remains on the sieve, the hardness cannot be measured. It is reasonably estimated to be lower than the hardness of the gel composition.

In the present invention, the high hardness stability of the gel composition means that the texture of the composition is maintained even after storage under severe conditions (eg, high temperature and/or long term).
The texture of the composition is closely related to the suppression of syneresis and the maintenance of hardness.

Method for Producing Oral Gel Composition The oral gel composition of the present invention may be produced by adopting a known method for producing an oral gel composition.
(1) a step of mixing the thickening agent and water (e.g., purified water) and then heating to dissolve the thickening agent;
(2) It can be produced by a production method including a step of mixing ingredients other than the thickening agent and water with the liquid obtained in step (1) to obtain a liquid composition.
The ingredients other than the thickening agent and water may optionally be premixed prior to mixing with the liquid obtained in step (1).

Packaging of Oral Gel Composition The oral gel composition of the present invention is packaged in a packaging that is commonly employed for gel compositions that are orally administered or ingested. The packaging may be carried out by a conventional method depending on the form.
In particular, the oral gel composition of the present invention has high stability in gel form even under severe conditions and can stably contain vitamin _B1 , so that there is little restriction on the conditions of the packaging process.
Therefore, various packaging methods can be easily and suitably adopted for the oral gel composition of the present invention.

The oral gel composition can be packaged, for example, by filling a container with the liquid composition obtained by the method for producing the oral gel composition.
Preferable examples of such packaging include pouch-type container packaging.

As the pouch-type container, a commonly used one can be used, for example, formed from a film material in which aluminum foil and resin film (e.g., polyethylene terephthalate, nylon, polyethylene, and combinations thereof) are laminated. You can use a pre-made container.
Said pouch-type container is a retort-sterilizable container, ie a retort pouch container.
The pouch-type container is of any type, such as a standing bag type, a gusset bag type, or a three-sided bag type.
Said pouch-type container is preferably provided with a spout. According to this, oral administration or oral intake can be easily performed.
The oral gel composition of the present invention enclosed in one pouch-type container is, for example, within the range of 80 mL to 300 mL.

Also provided is an oral gel composition of the present invention packaged in a pouch-type container, as understood from the foregoing description.
In particular, the oral gel composition of the present invention has high stability in gel form even under severe conditions and can stably contain vitamin _B1 , so that the conditions for the packaging process are less limited. Easily and conveniently packaged in pouch-type containers.

As will be understood from this, the present invention also provides an oral gel composition of the present invention and a bag formulation (pouch formulation or pouch-type formulation) comprising a pouch-type container enclosing the oral gel composition. do.

The bag formulation is preferably substantially free of liquids.
Specifically, in the pouch formulation, pouch-type formulation, or bag formulation, the amount of liquid in the entire contents is preferably 10% by mass or less, more preferably 5% by mass or less, and still more preferably 3% by mass. % or less.

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the present invention is not limited thereto. In the examples, "%" means "w/w %" unless otherwise specified.

An oral gel composition was prepared using the following materials. The jelly strength is a value measured according to JIS K 8263:2015 described above.
[material]
- Agar as a thickening agent:
Agar end PS-88 (product name, Ina Food Industry)
(Jelly strength: 950-1150 g/cm ² )
Agar end PS-6 (product name, Ina Food Industry)
(Jelly strength: 600-660 g/cm ² )
・ Fursultiamine hydrochloride (hereinafter also referred to as TTFD)
・Citrate buffer 0.2M

1.5 mg fursultiamine hydrochloride (TTFD) and 50 mL citrate buffer (0.2 M) at pH 2.8, 3.1, 3.4, 3.8, and 300 mg of agar as a thickener [agar end PS-88 (Example 1), agar end PS-6 (Comparative Example 1)] was heated and stirred to dissolve TTFD and agar, and purified water was added to make 100 mL. made it
Aluminum pouches with spouts were filled with the obtained solutions to obtain gel compositions of pH 2.8, 3.1, 3.4 and 3.8.

Test example (preservation test)
[1] Stability of fursultiamine hydrochloride (TTFD) Each gel composition of pH 2.8, 3.1, 3.4, and 3.8 produced as Example 1 was heated at 50°C, Stored for 8 weeks.
The amount of TTFD after storage at 50°C for 8 weeks was measured, and its residual rate (residual rate compared with the initial content immediately after production) was calculated. The residual rate (%) is shown in Table 1.

From the results in Table 1, in storage under severe conditions at 50 ° C. for 8 weeks, the amount of TTFD remained in a high proportion at any pH, and in particular in the pH range of 3.1 to 3.4, a higher proportion ( 80% or more) remained.

[2] Separation of Gel Composition Each gel composition was stored at 50° C. and 4° C. (control) for 8 weeks. The difference of [(water syneresis after storage at 50° C. for 8 weeks)−(water syneresis after storage at 4° C. for 8 weeks)] was calculated.
Table 2 shows the difference in the separation rate.

<Method for measuring syneresis of gel composition>
In the measurement method, a mesh with an opening of 2 mm [Japanese Pharmacopoeia 17th Edition, Sieve No. 8.6 (2000 μm)] and a diameter of 200 mm were used as the sieve. After placing the gel composition to be tested in a container and exposing it to predetermined storage conditions, the total amount of the contents of the container is placed on a sieve with a sieve under the sieve, the mass is measured, and the mass is A ( g). After the sieve was tilted at 45 degrees and held for 1 minute, the mass of the liquid (water syneresis) that fell from the sieve to the bottom of the sieve was measured.
Separation rate (%) = B (g) / A (g) x 100

From the results in Table 2, the gel composition of the present invention suppressed syneresis at any pH, and particularly at pH 3.1 or higher, syneresis was highly suppressed.

[3] Hardness of gel composition After storage of each gel composition [after storage at 50 ° C. or 4 ° C. (control) for 8 weeks] hardness was measured by the following method, and the ratio (50 ° C./ Control) was calculated, and the hardness and its ratio are shown in Table 3.

<Method for testing hardness of gel composition>
For this test, a material testing machine EZ-SX (product name, Shimadzu Corporation) capable of measuring the compressive stress of a substance by linear motion (load cell: 50 N, test jig: universal design hood test Set, software: TRAPEZIUM X texture, constant temperature device: cold and hot constant temperature device) were used.
The sample is filled into a container (diameter 40 mm, height 20 mm) to a height of 15 mm, and using the material testing machine, a resin circular plunger (diameter 20 mm, height 8 mm) is compressed at a compression rate of 10 mm / sec, and It was compressed twice under the condition of a clearance of 5 mm, and the compressive stress at that time was measured. The measurement was carried out at 20±2°C after the gel was placed in a 20°C constant temperature bath and stabilized at 20°C.
The maximum value of compressive stress in two compressions was taken as the hardness of the sample.

The hardness of the gel composition after storage [after storage at 50°C or 4°C (control) for 8 weeks] was measured by the above method, and the ratio (after storage at 50°C for 8 weeks/control) was calculated.
The hardness and its ratio are shown in Table 3.
In the table, "ND" indicates that no gel composition remained on the sieve and its hardness could not be measured. This indicates that the gel-like morphology of the gel-like composition, especially its moderate hardness, was not or hardly maintained.

From the results in Table 3, the oral gel composition of the present invention exhibited a moderate degree of stability at any pH when stored under severe conditions at 50°C for 8 weeks, compared to the gel compositions of the comparative examples. A high degree of hardness was maintained. Especially at pH 3.1 or higher, syneresis was suppressed to a very high degree.
Furthermore, in the range of pH 3.1 to pH 3.4, it was shown that both TTFD and gel-like morphology were highly maintained even after storage under severe conditions at 50°C for 8 weeks.

Formulation example 1
A container-packed oral gel composition containing "Fursultiamine hydrochloride (TTFD)" as a vitamin B class ₁ and "Agar powder PS-88 (Ina Food Industry)" as a thickening agent according to the formulation in Table 4. (pH adjusted to 3.4) was prepared.

The hardness of the oral gel composition of Formulation Example 1 was measured by the method described above and found to be 0.11 to 0.20N (measured values were 0.113N, 0.162N, and 0.137N).

Formulation example 2
According to the formulation in Table 5, a container _- packed oral gel composition (pH is 3.1) was prepared.
The jelly strength of agar powder T-1 is about 950 g/cm ² .

Formulation example 3
According to the formulation in Table 6, _a packaged oral gel composition (pH
was adjusted to 3.1) was prepared.

According to the present invention, by containing vitamin _B1 and a thickening agent having a jelly strength within the range of 700 to 1500 g/cm ² and adjusting the pH within the range of 2.8 to 3.8 , vitamin _B1 group stably, and an oral gel composition having a stable gel form is provided.

Claims (7)

An oral gel composition containing vitamin _B1 and a thickening agent having a jelly strength in the range of 700 to 1500 g/cm ² and having a pH in the range of 2.8 to 3.8. Vitamin B ₁ is thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate, dicetiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octotiamine, sicotiamine, bis-butiamine, bis 2. The oral gel composition according to claim 1, which is one or more selected from the group consisting of bentiamine, prosultiamine, and benfotiamine. 3. The oral gel composition according to claim 1 or 2, wherein the thickening agent is agar. The oral gel composition according to claim 3, wherein the reducing sugar content of the agar is 0.02% to 0.05% by weight. Oral gel composition according to any one of claims 1 to 4, wherein the hardness is within the range of 0.08 to 0.35N. The oral gel composition according to any one of claims 1 to 5, which is used as a pharmaceutical or quasi-drug. The oral gel composition according to any one of claims 1 to 6, which is packaged in a pouch-type container.