JP2023144045A - Oral gel-like composition - Google Patents

Abstract

To provide an oral gel-like composition which comprises vitamins B1 stably and has a stable gel-like form.SOLUTION: There is provided an oral gel-like composition which comprises vitamins B1 and gellan gum, where the oral gel-like composition comprises 10 to 2000 pts.mass of gellan gum based on 1 pt.mass of vitamins B1.SELECTED DRAWING: None

Description

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

Vitamin _B1 class is known to have various usefulness for living organisms, and is widely used in orally ingested pharmaceuticals, quasi-drugs, foods, and the like.
Tablets and drinks are the most suitable forms for ingesting vitamin B ₁ in sufficient quantities, but in recent years, fluid, viscous gel-like oral preparations have also become popular. Increasingly, it is being adopted as a
The reason behind the adoption of such gel preparations is that consumers prefer forms that are easy to administer, ingest, and swallow, especially in relation to the increase in the number of people with swallowing disorders due to the increasing number of elderly people in developed countries. It is thought that there are several reasons for this, such as the fact that a form that can be easily taken in a short period of time and that reduces the feeling of hunger is preferred.

A known technology similar to an oral gel preparation containing vitamin B ₁ type is an oral jelly containing 0.01 to 0.5% by weight of vitamin B ₁ type and 0.5 to 30% by weight of chondroitin sulfate. (Patent Document 1), but the oral jelly is a shaped gel-like preparation with no fluidity, and is not a liquid or fluid viscous gel-like preparation.

Japanese Patent Application Publication No. 2011-231051

According to the studies conducted by the present inventors, it is possible to realize an oral gel composition that stably contains vitamin B ₁ , and that the gel form is stable even under heat load during production, especially under acidic conditions. It is difficult to realize _an oral gel-like composition containing vitamin B ₁ type with little syneresis and a desired texture (hardness). It is even more difficult to realize stable oral gel compositions.

Therefore, in the present invention, a product that stably contains vitamin B ₁ and has a stable gel-like form, has little syneresis over time, and has a good texture (hardness) even under the heat load during production, especially under acidic conditions. The purpose of the present invention is to provide a stable oral gel composition.

As a result of extensive studies, the present inventors found that the product contains vitamin B ₁ class and gellan gum, and gellan gum is contained in a range of 10 to 2000 parts by mass per 1 part by mass of vitamin B ₁ class. The inventors have discovered that the above-mentioned problems can be solved by an oral gel composition characterized by the following, and have completed the present invention.

That is, the present invention includes the following aspects.
[1] An oral gel composition containing vitamin B ₁ class and gellan gum, and containing gellan gum in an amount of 10 to 2000 parts by mass per 1 part by mass of vitamin B ₁ class. .
[2] An oral gel composition containing vitamin B ₁ and gellan gum, and having a gellan gum content of less than 3.0 g/L.
[3] An oral gel composition containing vitamin B ₁ and gellan gum, and having a pH within the range of 2.5 to 3.8.
[4] The oral gel composition according to any one of [1] to [3] above, which is used as a pharmaceutical or quasi-drug.
[5] Vitamin B Type ₁ includes thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate, dicethiamine hydrochloride, fursulthiamine, fursulthiamine hydrochloride, octothiamine, cycothiamine, bis-ibub. The oral gel composition according to any one of [1] to [4] above, which is one or more selected from the group consisting of thiamine, bisbenchiamine, prosulthiamine, and benfotiamine.

According to the present invention, there is provided an oral gel composition that stably contains vitamin B ₁ and also has a stable gel form. In particular, the present invention provides an oral gel composition that exhibits little syneresis over time and has a stable texture (hardness) even under heat load during production under acidic conditions.

As used herein, the term "gel composition" refers to a fluid, viscous liquid composition, as distinguished from a solid gel composition.

Unless otherwise specified, symbols and abbreviations in this specification are understood to have the meaning commonly used in the technical field to which the present invention pertains.
The steps, treatments, or operations described herein are performed at room temperature, unless otherwise specified. As used herein, room temperature means a temperature within the range of 10 to 35°C.

Oral Gel Composition The oral gel composition of the present invention contains vitamin B ₁ and gellan gum.
Hereinafter, the components contained in the oral gel composition of the present invention and the components that may be contained will be explained.

・Vitamin B type ₁
Examples of vitamin B ₁ used in the present invention include thiamine, bisthiamine, thiamine disulfide, dicethiamine, fursulthiamine, octothiamine, cycothiamine, bisbuthiamine, bisbenthiamine, prosulthiamine, and benfotiamine, and It includes salts, solvates (eg, hydrates), and solvates (eg, hydrates) of salts. Examples of such salts include hydrochloride, nitrate, and cetyl sulfate.

The vitamin B ₁ type is preferably thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate, dicethiamine hydrochloride, fursulthiamine, fursulthiamine hydrochloride, octothiamine, cycothiamine, bisthiamine. It can be one or more selected from the group consisting of butiamine, bisbenthiamine, prosultiamine, and benfotiamine.
The vitamin _B1 class particularly preferably used in the present invention is fursultiamine or its hydrochloride.

The amount of vitamin B ₁ 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 entire composition. , more preferably about 0.0005 to 0.05 w/v%, still more preferably about 0.001 to 0.03 w/v%.

・Active ingredients other than vitamin B type ₁
The oral gel composition of the present invention may contain active ingredients other than vitamin B ₁ , such as pharmaceuticals and pharmaceuticals, including vitamins other than vitamin B ₁ , amino acids, etc., as long as they do not impair the effects of the present invention. Other products used in quasi products, foods with health claims (e.g., foods with functional claims, foods with nutritional function claims, foods for specified health uses), or general foods (e.g., nutritional supplements, health supplements, nutrition-adjusted foods), etc. It may further contain one or more active ingredients.

Examples of vitamins other than the vitamin B ₁ type include vitamin A types (e.g., retinol, retinoic acid, retinal, retinol acetate, retinol palmitate, vitamin A oil, liver oil, strong liver oil), vitamin B ₂ types [ Examples: Riboflavin, riboflavin derivatives (e.g. riboflavin esters such as riboflavin phosphate, riboflavin acetate, riboflavin butyrate; sodium flavin adenine dinucleotide, etc.) and their salts (e.g. sodium riboflavin phosphate)], vitamin B ₆ [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 B ₁₂ (e.g. cobalamin, cyanocobalamin, methylcobalamin, adenosylcobalamin, hydroxocobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate), vitamin C (e.g. Ascorbic acid, magnesium ascorbate phosphate, sodium ascorbate, calcium ascorbate, tocopheryl acetate ascorbate), vitamin D (e.g. ergocalciferol, cholecalciferol), vitamin E (e.g. d-succinate) α-tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, d-α-tocopherol calcium succinate, tocopherol calcium 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 K, biotin, folic acid, γ-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, mixture of equal amounts of potassium and magnesium aspartate), glutamic acid (e.g. -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 (aminoethyl sulfonic 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, ammonium citrate, ferrous fumarate, glucuronolactone, glucuronic acid, glucuronide 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, yoclecithin, rutin, and herbal medicines ( Examples: Asenyaku, fennel, eleuthero, oleracea, processed daisan, guarana, licorice, wolfberry, keihi, red ginseng, saffron, hawthorn, sanyaku, peony, shukusha, ginger, jyoteishi, hawthorn, Japanese radish, clove, chimpi, touki, toshishi , Eucommia, Nikujuyou, carrot, garlic, Japanese bush clover, Muirabuama, Mokko, Yakuchi, Japanese daisy, Longannik, Rokujo, Kaiba, Nikujuyou, bald citrus, Astragalus, sandalwood, royal jelly), and combinations thereof.

The amount of these active ingredients other than the vitamin B ₁ class is appropriately set depending on the type, purpose, etc.

・Gellan gum
In the present invention, various gellan gums can be suitably used. For example, native type (HA) gellan gum, deacylated (LA) gellan gum, etc. can be used. In the case of deacylated gellan gum, it is preferable to use it in combination with an appropriate amount of calcium ion, which is generally used to gel the deacylated gellan gum.
Such gellan gums are commercially available, such as various native type (HA) gellan gums and deacylated (LA) gellan gums sold by San-Eigen FI, Kelcogel ^(R) (product name, CP Kelco). US, Inc.).

As a result of extensive studies, the present inventors found that it is desirable to contain gellan gum in a range of 10 to 2000 parts by mass per 1 part by mass of vitamin _B1 .
Therefore, the content of gellan gum used in the present invention is preferably within the range of 10 to 2000 parts by mass, more preferably 15 to 1500 parts by mass, and 20 to 1500 parts by mass, per 1 part by mass of vitamin B ₁ . Particularly preferred is a range of 1000 parts by mass.

Further, the content of gellan gum in the oral gel composition of the present invention is preferably less than 3.0 g/L, more preferably less than 2.8 g/L, even more preferably 0.5 g/L, based on the entire composition. L~2.5g/L.

・Additional ingredients other than gellan gum
In the oral gel composition of the present invention, in addition to the above-mentioned ingredients, other ingredients, such as ingredients that can generally be added to oral gel compositions (e.g. sweetener , flavoring agent, preservative, preservative, flavoring agent, aromatic agent, cooling agent, surfactant, solubilizer, emulsifier, solvent, pH adjuster, buffering agent, suspending agent, coloring agent, stabilizer , an antifoaming agent, a solubilizing agent, a bitter taste masking agent, and a thickening agent other than gellan gum).

Examples of sweeteners are sugars (e.g. glucose, galactose, fructose, sucrose, lactose, maltose, high fructose sugar, liquid sugar, invert liquid sugar, trehalose), polysaccharides (e.g. oligosaccharides, starch), sugars Alcohols (e.g. erythritol, xylitol, maltitol, sorbitol, reduced maltose starch syrup, powdered reduced maltose starch syrup), high intensity sweeteners (e.g. acesulfame potassium) and non-carbohydrate sweeteners (e.g. sucralose, stevia extract, saccharin, aspartame), and combinations thereof.
Examples of flavoring agents include citric acid or its hydrate, sodium citrate, acidulants such as 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 parabenzoate, butyl parabenzoate, propyl parabenzoate), and combinations thereof.
Examples of flavoring, aromatic or cooling agents are orange oil, menthol, vanillin and its derivatives (e.g. ethyl vanillin), and various flavorings (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, condiment flavor), and combinations thereof.
Examples of surfactants include sucrose fatty acid ester, 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 purified soybean lecithin, soybean lecithin, soybean oil, medium chain fatty acid triglycerides, macrogol 4000, macrogol 6000, liquid paraffin, sucrose fatty acid esters, polyoxyethylene hydrogenated castor oils, and polysorbate 80. and combinations thereof.
Examples of emulsifiers include sucrose fatty acid esters, polyoxyethylene hydrogenated castor oils, polysorbate 20, polysorbate 80, purified soy lecithin, soy lecithin, medium chain fatty acid 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 adjusting agents or buffers are phosphoric acid, lactic acid, acetic acid, carbonic acid and their salts, hydrochloric acid, sodium hydroxide, potassium hydroxide, citric acid buffer (0.2M), and sodium bicarbonate; including combinations of
Examples of suspending agents include gum arabic, microcrystalline cellulose, vegum, xanthan gum, guar gum, gelatin, metrose and its salts, carmellose and its salts, and combinations thereof.
Examples of colorants include caramel, β-carotene, and various food colors (eg, Food Yellow No. 1, Food Red No. 2), and combinations thereof.
Examples of stabilizers include silicone resins, glycerin, salts of edetate, sodium chloride, and salts of pyrosulfite, and combinations thereof.
Examples of antifoam agents include silicone resins, silicone oils, ethanol, glycerin fatty acid esters, dimethylpolysiloxanes, sucrose fatty acid esters, polyoxyl stearates, sosurbitan fatty acid esters, sorbitan trioleate, and polysorbate 80, and combinations thereof. include.
Examples of solubility aids include propylene glycol, cyclodextrin, and arginine, and combinations thereof.
Examples of bitter taste masking agents include phosphatidyl compounds [eg BMI-60 (product name, Kao)].
Examples of thickening agents other than gellan gum include agar, xanthan gum, and guar gum, and combinations thereof.

The amounts of these additional components are appropriately set depending on the type, purpose, and the like.

pH of oral gel composition
In order to provide an oral gel composition that stably contains vitamin B ₁ (e.g., fursultiamine or its hydrochloride) and stably maintains its gel form, the present inventors It has been found that the upper limit of the pH of the composition is preferably 3.8 or less, more preferably 3.6 or less, and still more preferably 3.5 or less. It has also been found that the lower limit of the pH of the composition is preferably 2.5 or higher, more preferably 2.8 or higher, even more preferably 3.1 or higher, and particularly preferably 3.3 or higher.
That is, the pH of the oral gel composition of the present invention is preferably within the range of 2.5 to 3.8, more preferably within the range of 2.5 to 3.6, even more preferably 2.8 to 3.8. It is within the range of 1.

The pH may be adjusted, for example, by using the above-mentioned pH adjusters or buffers.
In measuring the pH of the oral gel composition in the present invention, the composition is finely divided using a commercially available food mixer to form a homogeneous solution, and then the pH measurement is performed as described in the Japanese Pharmacopoeia General Test Methods. All you have to do is conduct the test in accordance with the law.

Form of Oral Gel Composition The oral gel composition of the present invention can be used, for example, as an oral liquid preparation defined in the General Preparations of the 17th Edition of the Japanese Pharmacopoeia, that is, a liquid or fluid viscous preparation for oral administration. It can be suitably used as a gel-like preparation.
It is judged in light of common general technical knowledge that the preparation is not a solid preparation such as a gel, but a liquid or fluid viscous gel preparation.

The viscosity of a gel composition can be indicated by the hardness of the gel composition, and a gel composition with high hardness can be said to have high viscosity.
The oral gel composition of the present invention preferably has a hardness of 0.05N or more, more preferably 0.08N or more, and even more preferably 0.10N or more, as measured by the test method described below, for example. By having such hardness, the oral gel composition of the present invention can prevent aspiration and is easy to administer or ingest.
The hardness of the oral gel composition of the present invention is preferably 0.50N or less, more preferably 0.35N or less, even 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 within the range of 0.05 to 0.50N, more preferably within the range of 0.08 to 0.35N, even more preferably 0.10 to 0. It is within the range of .30N.

The oral gel composition of the present invention is orally administered or ingested.
The oral gel composition of the present invention can be used as a pharmaceutical, a quasi-drug, a food with health claims (e.g., a food with functional claims, a food with nutritional function claims, a food for specified health use), or a general food (e.g., a nutritional supplement, a health supplement). It can be used as food, nutrition-adjusted food), etc.

The oral gel composition of the present invention has high stability in its gel form.
In the present invention, the high stability of the gel-like form means the following physical properties:
(1) syneresis is suppressed even after storage under harsh conditions (e.g. high temperature, acidic and/or long term) and/or (2) syneresis is suppressed even after storage under harsh conditions (e.g. high temperature, acidic and/or long term); This means that the decrease in hardness is suppressed even after storage for a long period of time.
In addition, from a sensory point of view, it means that the texture of the gel composition is maintained.

Here, the measurement of the amount of water separation and the calculation of the water separation rate of the gel composition are carried out by the following measurement method.
<Method for measuring syneresis of gel composition>
In this measurement method, a sieve with a mesh opening of 2 mm [17th edition Japanese Pharmacopoeia, sieve number 8.6 (2000 μm)] and a diameter of 200 mm is used.
After placing the gel composition to be tested in a container and exposing it to the predetermined storage conditions, the entire contents of the container are placed on a sieve lined with a sieve bottom, its mass is measured, and the mass is calculated as A( g). Next, after tilting the sieve at 45 degrees and holding it for 1 minute, measure the mass of the liquid (water syneresis) that has fallen from the sieve to the bottom of the sieve, define this as B (g), and calculate the syneresis rate using the following formula. calculate.
Water separation rate (%) = B (g) / A (g) x 100

In the oral gel composition of the present invention, the high stability of the gel form means that the gel composition has an appropriate hardness even after storage under harsh conditions (e.g. high temperature, acidity and/or long term). is maintained.

The oral gel composition of the present invention preferably has a hardness ratio (defined as As understood from the above, the hardness ratio 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 was measured by the following measuring method using the gel composition remaining on the sieve as a sample in the method for measuring syneresis of a gel composition. be done.
<Testing method for hardness of gel composition>
For this test, we used a material testing machine EZ-SX (product name, Shimadzu Corporation) (product name, Shimadzu Corporation) (load cell: 50N, test jig: universal design hood test) that can measure the compressive stress of substances through linear motion. Set, software: TRAPEZIUM
The sample was filled into a container (diameter 40 mm, height 20 mm) to a height of 15 mm, and compressed at a compression speed of 10 mm/sec with a resin circular plunger (diameter 20 mm, height 8 mm) using the material testing machine. It is compressed twice under the condition of a clearance of 5 mm, and the compressive stress at that time is measured. Measurements are carried out at 20±2°C.
The maximum value of compressive stress in two compressions is defined as the hardness of the sample.

As a sample in this test, the gel composition remaining on the sieve is used in the method for measuring syneresis of the gel composition described above.
Therefore, if no gel-like composition remains on the sieve, the hardness cannot be measured, but as those skilled in the art would normally understand, if no gel-like composition remains on the sieve, the hardness is It is reasonably estimated that the hardness is lower than that of the gel composition.

In the present invention, the high stability of the hardness of the gel-like composition means that the texture of the composition is maintained even after storage under harsh conditions (e.g., high temperature, acidity 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 employing a known method for producing oral gel compositions, and specifically, for example,
(1) a step of mixing the gellan gum and water (e.g. purified water) and then heating to dissolve the gellan gum;
(2) It can be manufactured by a manufacturing method including a step of mixing components other than the gellan gum and water with the liquid obtained in step (1) to obtain a liquid composition.
Components other than the gellan gum and water may be mixed in advance, as appropriate, before 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 manner that is commonly used for gel compositions to be 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 a highly stable gel form even under severe conditions and can stably contain vitamin _B1 , so there are few restrictions on the conditions of the packaging process.
Therefore, various packaging methods can be easily and suitably employed 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 an oral gel composition.
A suitable example of such packaging is packaging in a pouch-type container.

As the pouch type container, a commonly used one can be used, and for example, it is 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 containers made with
The pouch-type container is a container that can be sterilized by retort, that is, 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.
The pouch-type container preferably includes a spout. According to this, it can be easily administered orally.
The oral gel composition of the present invention enclosed in one pouch-type container has a volume of, for example, in the range of 80 mL to 300 mL.

As can be understood from the foregoing description, there is also provided an oral gel composition of the present invention packaged in a pouch-type container.
In particular, the oral gel composition of the present invention has a highly stable gel form even under severe conditions, and can stably contain vitamin _B1 , so there are few restrictions on the conditions of the packaging process. It can be easily and conveniently packaged in a pouch-type container.

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

The bag formulation preferably contains substantially no liquid.
Specifically, in the pouch preparation, pouch-type preparation, or bag preparation, the amount of liquid in the entire contents is preferably 10% by mass or less, more preferably 5% by mass or less, and even more preferably 3% by mass. % or less.

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

[Example 1]
An oral gel composition was prepared using the materials shown in Table 1 below.

[Method for preparing gel composition]
(1) The materials listed in Table 1 ranging from fursultiamine hydrochloride ("TTFD" in the table) to magnesium chloride were dissolved in purified water in amounts per bag. Then, the pH of the obtained aqueous solution was adjusted to pH 2.5, pH 2.8, pH 3.1, pH 3.4, or pH 3.8 using appropriate hydrochloric acid and sodium hydroxide. Thereafter, these aqueous solutions were heated to 50°C.
(2) On the other hand, add the ingredients listed in the table from gellan gum (deacylated (LA) gellan gum, San-Eigen FI) to glucose into the same bag, mix, and add this mixture to purified water while stirring. and dissolved. This aqueous solution was heated in a microwave oven until it boiled.
(3) Each aqueous solution obtained in the above (1) and the aqueous solution obtained in the above (2) were mixed, and purified water was added to make 100 mL.
(4) The obtained solution was filled into an aluminum pouch with a stopper to obtain each gel composition having a pH of 2.5, 2.8, 3.1, 3.4, and 3.8.

[Example 2]
An oral gel composition was prepared using the following materials.
[material]
・Thickening agent:
Gellan gum (deacylated (LA) gellan gum, San-Ei Gen FFI)
Agar (Agar powder PS-6 (product name, Ina Foods Industry))
・Fursultiamine hydrochloride (hereinafter also referred to as TTFD)
・Citrate buffer 0.2M

The amount per bag is 1.5 mg of fursultiamine hydrochloride (TTFD) and 50 mL of citrate buffer (0.2 M) at pH 2.8, 3.1, 3.4, 3.8. 200 mg of gellan gum (Example 2) or 300 mg of agar (Comparative Example 1) were mixed by heating and stirring to dissolve TTFD and gellan gum or agar, and purified water was added to make 100 mL.
The obtained solution was filled into an aluminum pouch with a stopper to obtain each gel composition having a pH of 2.8, 3.1, 3.4, and 3.8.

[Test Example 1] Stability of fursultiamine hydrochloride (TTFD) Each of the gel compositions prepared as Example 1 with pH 2.5, 2.8, 3.1, 3.4, and 3.8 was tested. , each was stored at 60°C for 2 weeks.
The amount of TTFD after storage at 60° C. for 2 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 2.

From the results in Table 2, the amount of TTFD remained at a high rate at any pH during storage under severe conditions at 60° C. for 2 weeks.

[Test Example 2] Syneresis of gel composition After storing each gel composition at 50°C and 4°C (control) for 8 weeks, the amount of syneresis was measured using the measurement method described below, and the syneresis rate was calculated. From this, 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 3 shows the difference in water separation rate.

<Method for measuring syneresis of gel composition>
In this measurement method, a mesh with an opening of 2 mm [17th edition Japanese Pharmacopoeia, sieve number 8.6 (2000 μm)] and a sieve with a diameter of 200 mm was used as a sieve. After placing the gel-like composition to be tested in a container and exposing it to the predetermined storage conditions, the entire contents of the container are placed on a sieve lined with a sieve bottom, its mass is measured, and the mass is defined as A( g).
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 to the bottom of the sieve was measured, this was taken as B (g), and the water separation rate was calculated using the following formula.
Water separation rate (%) = B (g) / A (g) x 100

From the results in Table 3, in the gel composition of the present invention, syneresis was highly suppressed at any pH.

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

<Testing method for hardness of gel composition>
For this test, we used a material testing machine EZ-SX (product name, Shimadzu Corporation) (product name, Shimadzu Corporation) (load cell: 50N, test jig: universal design hood test) that can measure the compressive stress of substances through linear motion. Set, software: TRAPEZIUM
The sample was filled into a container (diameter 40 mm, height 20 mm) to a height of 15 mm, and compressed at a compression speed of 10 mm/sec with a resin circular plunger (diameter 20 mm, height 8 mm) using the material testing machine. 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 performed at 20±2°C after the gel was placed in a constant temperature bath at 20°C and stabilized at 20°C.
The maximum value of compressive stress in two compressions was defined 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 ratios are shown in Table 4.
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 very little maintained.

From the results in Table 4, it can be seen that the oral gel composition of the present invention, when stored under harsh conditions at 50°C for 8 weeks, showed a moderate level of Hardness was highly maintained.

Formulation example 1
According to the formulation in Table 5, it contains vitamin B ₁ class (fursultiamine hydrochloride) and 1.5 g/L of gellan gum (deacylated (LA) gellan gum, San-Ei Gen FFI), and contains 1 mass of vitamin B ₁ class. An oral gel composition containing 100 parts by mass of gellan gum (pH adjusted to 3.1) was prepared.

According to the present invention, by containing vitamin B ₁ class and gellan gum, and containing gellan gum in the range of 10 to 2000 parts by mass per 1 mass part of vitamin B ₁ class, vitamin B ₁ Provided is an oral gel composition that stably contains the following compounds and has a stable gel form.

Claims (4)

Contains vitamin B ₁ class and gellan gum, and contains gellan gum in the range of 10 to 2000 parts by mass per 1 part by mass of vitamin B ₁ class,
The amount of vitamin B ₁ is about 0.00005 to 0.5 w/v% of the entire composition,
pH is within the range of 2.5 to 3.4,
An oral gel composition characterized in that the vitamin B ₁ is fursultiamine or fursultiamine hydrochloride. The oral gel composition according to claim 1, having a pH within the range of 2.5 to 3.1. The oral gel composition according to claim 1 or 2, wherein the content of gellan gum is less than 3.0 g/L. The oral gel composition according to any one of claims 1 to 3, which is used as a pharmaceutical or quasi-drug.