JP2020164483A - 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 B vitamins ₁ .

Vitamin B ₁ class are known to have various utilities for biological, pharmaceutical products taken orally, it is widely used in the quasi-drug and foods.
Vitamin B ₁ class of the form to enable ingested in sufficient amounts, primarily but form such as a tablet or beverage is preferably employed, in recent years, also its form viscous gel oral formulations having fluidity The number of cases where it is adopted as is increasing.
Behind the adoption of such gel-like preparations, consumers prefer a form that is easy to administer or ingest and swallow, especially in relation to the increase in dysphagia associated with the increase in the elderly in developed countries. It is considered that there are reasons such as the fact that the drug can be easily ingested in a short time and a form that can reduce the feeling of hunger is preferred.

Known techniques closer to oral gel formulation containing vitamin _{B 1} class, 0.01-0.5 wt% of vitamin _{B 1} class, and oral jelly containing 0.5 to 30% by weight of chondroitin sulfate An agent (Patent Document 1) can be mentioned, but the oral jelly agent is a non-fluid, molded gel-like preparation, not a liquid or a fluid, viscous gel-like preparation.

Japanese Unexamined Patent Publication No. 2011-231051

According to the studies of the present inventors, realizing the oral gel composition stably containing vitamin B ₁ class, and gel-like forms are stable, even in the particular thermal load during production in acidic conditions, a time water separation is small, the desired implementation of the texture (firmness) of the oral gel compositions containing stable vitamins B ₁ class are each difficult, vitamin B ₁ class contains stable, besides a form of gel However, it is even more difficult to realize a stable oral gel composition.

Therefore, in the present invention contains a vitamin B ₁ class stability, and gel-like forms are also stable, in particular also in the thermal load during production in acidic conditions, less temporal water separation, texture (hardness) It is an object of the present invention to provide a stable oral gel composition.

The present inventors have intensive studies results, vitamin B ₁ class, and contains a gellan gum, and with respect to 1 part by weight of vitamin B ₁ class, the gellan gum such as that contained in the range of 10 to 2000 parts by weight It was found that the above-mentioned problems can be solved by the oral gel-like composition characterized by the above, and the present invention has been completed.

That is, the present invention includes the following aspects.
[1] An oral gel-like composition containing vitamin B ₁ and gellan gum, and containing gellan gum in the range of 10 to 2000 parts by mass with respect to 1 part by mass of vitamin B ₁ . ..
[2] An oral gel-like composition containing vitamin B ₁ and gellan gum and having a gellan gum content of less than 3.0 g / L.
[3] Vitamin _{B 1} class, and contains a gellan gum, and oral gel compositions wherein the pH is in the range of 2.5 to 3.8.
[4] The oral gel composition according to any one of the above [1] to [3], which is used as a drug or a quasi drug.
[5] vitamin B ₁ class is thiamine hydrochloride, thiamine nitrate, Bisuchiamin nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salts, dicethiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, oct thiamin, Shikochiamin, Bisuibu The oral gel-like composition according to any one of the above [1] to [4], which is one or more selected from the group consisting of thiamine, bisbenchamine, prosultiamine, and benfothiamine.

According to the present invention contains a vitamin B ₁ class stable, stable oral gel composition is provided and also a form of gel. In particular, according to the present invention, there is provided an oral gel-like composition having a stable texture (hardness) with little water separation over time even under a heat load during production under acidic conditions.

Terms As used herein, the term "gel composition" means a fluid, viscous liquid composition to distinguish it from a solid gel composition.

Unless otherwise specified, the symbols and abbreviations in the present specification are understood to have common meanings in the technical field to which the present invention belongs.
The steps, treatments, or operations described herein are performed at room temperature unless otherwise specified. In the present specification, room temperature means a temperature in the range of 10 to 35 ° C.

Oral gel compositions oral gel composition of the present invention, vitamin B ₁ class, and contains a gellan gum.
Hereinafter, the components contained in the oral gel composition of the present invention and the components that may be contained will be described.

Vitamin B ₁ class examples of vitamin B ₁ class used in the present invention, thiamine, Bisuchiamin, thiamine disulfide, dicethiamine, fursultiamine, oct thiamine, Shikochiamin, bis Eve thiamine, bisbentiamine, prosultiamine, and Ben Includes fotiamines and their salts, solvates (eg hydrates), and hydrates of salts (eg hydrates). Examples of such salts include hydrochlorides, nitrates, and cetyl sulfates.

The vitamin B ₁ class is suitably, thiamine hydrochloride, thiamine nitrate, Bisuchiamin nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salts, dicethiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, oct thiamin, Shikochiamin, bis It can be one or more selected from the group consisting of ibutyamine, bisbenchamine, prosultiamine, and benfothiamine.
Vitamin B ₁ class, particularly preferably used in the present invention is a Furusuruchiamin or its hydrochloride salt.

The blending amount of B vitamins 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%.

· In the oral gel composition of the active ingredient present invention other than vitamin B ₁ class, as long as it does not inhibit the effects of the present invention, the active ingredient other than vitamin B ₁ class, for example, vitamin B ₁ class other than vitamins, amino acids Pharmaceuticals, non-pharmaceutical products, foods with health claims (eg foods with functional claims, foods with nutritional claims, foods for specified health use), or general foods (eg dietary supplements, dietary supplements, nutritional adjustments) It may further contain one or more of other active ingredients used in foods) and the like.

Examples of vitamins other than vitamin B ₁ include vitamin A (eg, retinol, retinoic acid, retinal, retinol acetate, retinol palmitate, vitamin A oil, liver oil, strong liver oil), vitamin B ₂ [ Examples: riboflavin, riboflavin derivatives (eg, riboflavin esters such as riboflavin phosphate, riboflavin acetate, riboflavin butyrate; riboflavin ester such as flavin adenindinucleotide sodium) and salts thereof (eg, sodium riboflavin phosphate)], vitamin B ₆ Classes [eg, pyridoxin, pyridoxamine, pyridoxal, derivatives thereof (eg, pyridoxin phosphate, pyridoxal phosphate hydrate, pyridoxamine phosphate, pyridoxin palmitate) and salts thereof (eg, pyridoxin hydrochloride) , pyridoxal hydrochloride, pyridoxamine dihydrochloride), vitamin B ₁₂ compound (e.g. cobalamin, cyanocobalamin, methylcobalamin, adenosylcobalamin, hydroxocobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate), vitamin C (e.g. Ascorbic acid, magnesium ascorbic acid phosphate, sodium ascorbate, calcium ascorbate, tocopherol acetate ascorbic acid ester), vitamin Ds (eg ergocalciferol, cholecalciferol), vitamin Es (eg d-succinate) α-tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol succinate, d-α-tocopherol calcium succinate, tocopherol calcium succinate, d-α-tocopherol acetate, dl-α-tocopherol acetate, d -Α-tocopherol, dl-α-tocopherol), niacins (eg nicotinic acid, nicotinic acid amide), pantothenic acids (eg pantenol, calcium pantothenate, sodium pantothenate), and other vitamins (eg nicotinate) Vitamin Ks, biotin, folic acid, γ-orizanol), and combinations thereof.

Examples of the amino acids include aspartic acid (eg, L-aspartic acid, potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, potassium aspartate / magnesium equal amount mixture), glutamate (eg L). -Glutamic acid), arginine (eg L-arginine, L-arginine hydrochloride), tryptophan (eg L-tryptophan), lysine (eg L-lysine hydrochloride, L-lysine acetate), glycine, leucine (eg) : L-lysine), isoleucine (eg L-isoleucine), threonine (eg L-thionine), cysteine (eg L-cysteine, L-cysteine hydrochloride, L-cysteine hydrochloride hydrate), valine (eg) : L-valine), histidine (eg L-lysine, 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-orizanol, calcium citrate, calcium glycerate, calcium gluconate, Diisopropylamine dichloroacetate, calcium carbonate, precipitated calcium carbonate, calcium lactate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, ammonium iron citrate, ferrous fumarate, glucuronolactone, glucuronic acid, glucuronic acid amide, caffeine , Anhydrous caffeine, sodium chondroitin sulfate, inositol, glycyrrhizinic acid, sodium glycyrrhizinate, sodium gluconate, choline heavy tartrate, magnesium carbonate, thioctic acid, thioctic acid amide, dehydrocholic acid, pantetin, yoke lecithin, rutin, and crude drug ( Examples: Asenyaku, Uikyo, Ezokogi, Osei, Processed Daisan, Galana, Kanzo, Kukoshi, Keihi, Kojin, Saffron, Sanzashi, Sanyaku, Shakuyaku, Sukusha, Shokyo, Joteishi, Seiyousanzashi, Taiso , Tochu, Nikujuyo, Carrot, Carrot, Bukuryo, Muirabuama, Mokko, Yakuchi, Yokuinin, Ryugannik, Rokujo, Kaiba, Nikujuyo, Hagekiten, Ougi, Byakujutsu, Royal Jelly), and combinations thereof.

The amount of active ingredients other than these vitamins B ₁ class, the type, and depending on the purpose or the like is appropriately set.

-Gellan gum In the present invention, various gellan gums can be preferably used. For example, native type (HA) gellan gum, deacylated (LA) gellan gum and the like can be used. In the case of deacylated gellan gum, it is preferable to use it in combination with an appropriate amount of calcium ions generally used for gelling the deacylated gellan gum.
Such gellan gums are commercially available, for example, various native (HA) gellan gums and deacylated (LA) gellan gums, kercogels ^(R) (product name, CP Kelco ⁾ sold by Saneigen FFI. US, Inc.) and so on.

We, the present inventors have assiduously studied the results, with respect to 1 part by weight of vitamin B ₁ class, we have found that it is desirable to contain in the range of 10 to 2000 parts by weight of gellan gum.
Therefore, the content of gellan gum used in the present invention, with respect to 1 part by weight of vitamin _{B 1} class, preferably in the range of 10 to 2000 parts by weight, more preferably in the range of 15 to 1,500 parts by weight, 20 It is particularly preferably in the range of ~ 1000 parts by mass.

The content of gellan gum in the oral gel-like composition of the present invention is preferably less than 3.0 g / L, more preferably less than 2.8 g / L, still more preferably 0.5 g / L, based on the entire composition. It is L to 2.5 g / L.

-Additional components other than gellan gum In the oral gel-like composition of the present invention, other components, for example, generally an oral gel-like composition, can be added in addition to the above-mentioned components as long as the effects of the present invention are not impaired. Ingredients (eg sweeteners, flavoring agents, preservatives, preservatives, flavoring agents, air fresheners, cooling agents, surfactants, solubilizers, emulsifiers, solvents, pH adjusters, buffers, suspending agents, It may contain one or more of a colorant, a stabilizer, a defoaming agent, a solubilizing agent, a bitterness masking agent, and a thickening agent other than gellan gum).

Examples of sweeteners are sugars (eg glucose, galactose, fructose, sucrose, lactose, maltose, high fructose corn syrup, liquid sugar, converted liquid sugar, trehalose), polysaccharides (eg oligosaccharides, starch), sugars. Alcohols (eg erythritol, xylitol, martitol, sorbitol, reduced maltose syrup, powdered reduced maltose syrup), high-sweetness sweeteners (eg assesulfam potassium) and non-sugar sweeteners (eg sclarose, stevia extract, Includes saccharin, aspartame), and combinations thereof.
Examples of flavoring agents include citric acid or hydrates thereof, acidulants such as 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 paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate), and combinations thereof.
Examples of flavoring agents, fragrances or cooling agents include orange oil, menthol, vanillin and its derivatives (eg ethylvanillin), and various flavors (eg strawberry flavor, cherry flavor, orange flavor, grapefruit flavor, apple flavor). , Lemon flavor, grape flavor, coffee flavor, black tea flavor, bitter flavor, herb mint flavor, chocolate flavor, flavored sake flavor), and combinations thereof.
Examples of surfactants are sucrose fatty acid ester, propylene glycol, polyoxyethylene (160) polyoxypropylene (30) glycol (poloxamer 188), polyoxyethylene hydrogenated castor oil (eg, 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 triglyceride, macrogol 4000, macrogol 6000, liquid paraffin, sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil, and polysolvate 80. And include combinations thereof.
Examples of emulsifiers include sucrose fatty acid esters, polyoxyethylene hydrogenated castor oils, polysorbate 20, polysorbate 80, refined soybean lecithin, soybean lecithin, medium chain triglycerides, and liquid paraffins, 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 regulators or buffers are phosphoric acid, lactic acid, acetic acid, carbonic acid and salts thereof, hydrochloric acid, sodium hydroxide, potassium hydroxide, citrate buffer (0.2M), and sodium hydrogen carbonate, and they. Includes combinations of.
Examples of suspending agents include gum arabic, crystalline cellulose, bee gum, xanthan gum, guar gum, gelatin, metros and salts thereof, carmellose and salts thereof, and combinations thereof.
Examples of colorants include caramel, β-carotene, and various food dyes (eg, Food Yellow No. 1, Food Red No. 2), and combinations thereof.
Examples of stabilizers include silicone resins, glycerin, salts of edetic acids, salts of sodium chloride, and sodium metabisulfite, and combinations thereof.
Examples of defoamers include silicone resins, silicone oils, ethanol, glycerin fatty acid esters, dimethylpolysiloxane, sucrose fatty acid esters, polyoxyl stearyl acid, sosulfitan fatty acid esters, sorbitan trioleate, and polysorbate 80, and combinations thereof. Include.
Examples of solubilizers include propylene glycol, cyclodextrin, and arginine, and combinations thereof.
Examples of bitter masking agents include phosphatidyls [eg BMI-60 (product name, Kao)].
Examples of thickeners other than gellan gum include agar, xanthan gum, and guar gum and combinations thereof.

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

PH of oral gel composition
In order to provide an oral gel-like composition that stably contains vitamin B ₁ (eg, fursultiamine or a hydrochloride thereof) and stably retains a gel-like form, the present inventors have said that. 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, 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 more, more preferably 2.8 or more, still more preferably 3.1 or more, and particularly preferably 3.3 or more.
That is, the pH of the oral gel composition of the present invention is preferably in the range of 2.5 to 3.8, more preferably in the range of 2.5 to 3.6, and even more preferably in the range of 2.8 to 3. It is within the range of 1.

The pH may be adjusted, for example, by using the above-mentioned pH adjuster or buffer.
In measuring the pH of the oral gel-like composition in the present invention, the composition is refined using a commercially available food mixer to prepare a homogeneous solution, and then the pH is measured according to the Japanese Pharmacopoeia / General Test Method. The test may be conducted in accordance with the law.

Form of Oral Gel-like Composition The oral gel-like composition of the present invention is, for example, an oral liquid preparation specified in the 17th revised Japanese Pharmacopoeia General Formulation Regulations, that is, "orally administered, liquid or fluid viscous". It can be suitably used as a “gel-like preparation”.
It is judged in light of common general knowledge that the preparation is not a solid preparation such as a gel, but a liquid or fluid viscous gel-like preparation.

The consistency of the gel-like composition can be indicated by the hardness of the gel-like composition, and it can be said that the gel-like composition having a large hardness has a high viscosity.
The oral gel composition of the present invention has, for example, a hardness measured by the test method described later, preferably 0.05 N or more, more preferably 0.08 N or more, still more preferably 0.10 N or more. By having such hardness, the oral gel-like composition of the present invention can prevent aspiration and is easy to administer or ingest.
The oral gel composition of the present invention has a hardness of preferably 0.50 N or less, more preferably 0.35 N or less, still more preferably 0.30 N or less. By having such hardness, the oral gel-like composition of the present invention is easy to administer or ingest.
The oral gel-like composition of the present invention has a hardness preferably in the range of 0.05 to 0.50 N, more preferably in the range of 0.08 to 0.35 N, and further preferably in the range of 0.10 to 0. It is in the range of .30N.

The oral gelled composition of the present invention is orally administered or orally ingested.
The oral gel composition of the present invention is a pharmaceutical product, a non-pharmaceutical product, a food with health claims (eg, food with functional claims, food with nutritional function, food for specified health use), or a general food (eg, dietary supplement, health supplement). It can be used as food, nutritionally adjusted food), etc.

The oral gel-like composition of the present invention has a high stability in its gel-like form.
In the present invention, the fact that the gel-like form has high stability means that, in terms of physical properties,
(1) Suppression of water separation even after storage under harsh conditions (eg high temperature, acidity and / or long term) and / or (2) harsh conditions (eg high temperature, acidity and / or long term) / Or even after storage for a long period of time), it means that the decrease in hardness is suppressed.
Also, sensually, it means that the texture of the gel-like composition is maintained.

Here, the measurement of the amount of water separation and the calculation of the water separation rate of the gel-like composition are carried out by the following measurement methods.
<Measuring method of water separation of gel-like composition>
In the measuring method, a mesh having a mesh opening of 2 mm [17th revision Japanese Pharmacopoeia, sieve number 8.6 (2000 μm)] and a sieve having a diameter of 200 mm are used as a sieve.
After the gelled composition to be tested is placed in a container and exposed to predetermined storage conditions, the entire contents of the container are placed on a sieve under a sieve, the mass is measured, and the mass is A ( g). Next, after tilting the sieve by 45 degrees and holding it for 1 minute, the mass of the liquid (water separation) that fell from the sieve under the sieve was measured, and this was defined as B (g), and the water separation rate was calculated by the following equation. 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 is the appropriate hardness of the gel composition even after storage under harsh conditions (eg, high temperature, acidity and / or long term). Is maintained.

The oral gel composition of the present invention is preferably the ratio of hardness when stored in a refrigerator (ie, at about 4 ° C.) for 8 weeks to hardness when stored at 50 ° C. for the same period (this definition). As can be understood from the above, the hardness ratio may exceed 100%), but is preferably 65% or more, more preferably 70% or more, still more preferably 80% or more.

The hardness of the oral gel-like composition of the present invention is measured by the following measurement method using the gel-like composition remaining on the sieve as a sample in the method for measuring water separation of the gel-like composition. Will be done.
<Test method for hardness of gel-like composition>
For this test, as a material tester, the material tester EZ-SX (product name, Shimadzu Corporation) (load cell: 50N, test jig: universal design hood test) that can measure the compressive stress of a substance by linear motion. Set, software: TRAPEZIUM X texture, thermostat: cold thermostat), or equivalent.
The sample was filled in a container (diameter 40 mm, height 20 mm) up to a height of 15 mm, and using the material tester, a resin circular plunger (diameter 20 mm, height 8 mm) was used to compress the sample at a compression rate of 10 mm / sec. Compress twice under the condition of a clearance of 5 mm, and measure the compressive stress at that time. The measurement is performed 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-like composition remaining on the sieve is used in the method for measuring water separation of the gel-like composition.
Therefore, if the gel-like composition does not remain on the sieve, the hardness cannot be measured, but as those skilled in the art usually understand, if the gel-like composition does not remain on the sieve, the hardness remains on the sieve. It is reasonably estimated that the hardness is lower than that of the gel-like composition.

In the present invention, the high hardness stability of the gel-like composition maintains the texture of the composition even after storage under harsh conditions (eg, high temperature, acidity and / or long term). ..
The texture of the composition is closely related to the suppression of water separation and the maintenance of the hardness.

Method for Producing Oral Gel-like Composition The oral gel-like composition of the present invention may be produced by adopting a known method for producing an oral gel-like composition. Specifically, for example,
(1) A step of mixing the gellan gum and water (eg, purified water) and then heating to dissolve the gellan gum.
(2) It can be produced by a production method including a step of mixing the components other than gellan gum and water with the liquid obtained in the step (1) to obtain a liquid composition.
The components other than gellan gum and water may be appropriately mixed in advance before being mixed with the liquid obtained in the step (1).

Packaging of Oral Gel-like Composition The oral gel-like composition of the present invention is provided with the packaging usually used for a gel-like composition to be orally administered or orally ingested. The packaging may be carried out by a conventional method according to the form.
In particular, oral gel composition of the present invention, even under severe conditions, has a form of gel stability is high, and since the vitamin B ₁ class can stably contains smaller restriction conditions of the packaging process.
Therefore, various packaging methods can be easily and preferably adopted for the oral gel-like composition of the present invention.

The packaging of the oral gel-like composition can be carried out, for example, by filling the container with the liquid composition obtained by the method for producing the oral gel-like composition.
A suitable example of such packaging is packaging in a pouch-type container.

As the pouch-type container, a general-purpose container can be used, and is formed of, for example, a film material in which aluminum foil and a resin film (eg, polyethylene terephthalate, nylon, and polyethylene, and a combination thereof) are laminated. Can be used in the container.
The pouch-type container is a retort-sterilizable container, 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 comprises a spout. According to this, it can be easily orally administered or orally ingested.
The oral gel composition of the present invention enclosed in one pouch-type container is, for example, in the range of 80 mL to 300 mL.

As understood from the above description, the oral gel composition of the present invention, which is packaged in a pouch-type container, is also provided.
In particular, oral gel composition of the present invention, even under severe conditions, a form of gel has a high stability, and because vitamin B ₁ class can stably contains smaller restriction conditions of the packaging process, Easily and preferably packaged in a pouch-type container.

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

The bag formulation preferably contains substantially no liquid.
Specifically, in the pouch preparation, the pouch type preparation, or the back preparation, the amount of the liquid to be added to the entire contents is preferably 10% by mass or less, more preferably 5% by mass or less, still more preferably 3% by mass. % Or less.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto. In the examples, unless otherwise specified, "%" means "w / w%".

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

[Method for preparing gel-like composition]
(1) As the amount per bag, the materials from fursultiamine hydrochloride (“TTFD” in the table) to magnesium chloride shown in Table 1 were dissolved in purified water. Then, the pH of the obtained aqueous solution was adjusted to one of pH 2.5, pH 2.8, pH 3.1, pH 3.4, and pH 3.8 by appropriately using hydrochloric acid and sodium hydroxide. Then, these aqueous solutions were heated to 50 ° C.
(2) On the other hand, the ingredients from gellan gum (deacyl type (LA) gellan gum, Saneigen FFI) to glucose in the table are added to the same bag and mixed, and this mixture is added to purified water with stirring. And dissolved. The aqueous solution was heated in a microwave until it boiled.
(3) Each aqueous solution obtained in (1) above was mixed with the aqueous solution obtained in (2) above, and purified water was added to make 100 mL.
(4) The obtained solution was filled in an aluminum pouch with a spout to obtain gel-like compositions having pH 2.5, 2.8, 3.1, 3.4, and 3.8.

[Example 2]
The oral gel composition was prepared using the following materials.
[material]
・ Viscous agent:
Gellan gum (deacyl type (LA) gellan gum, Saneigen FFI)
Agar (Kanten powder PS-6 (product name, Ina Food Industry))
-Fursultiamine hydrochloride (hereinafter also referred to as TTFD)
・ Citric acid buffer 0.2M

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

[Test Example 1] Stability of Fursultiamine Hydrochloride (TTFD) Gel-like compositions having pH 2.5, 2.8, 3.1, 3.4, and 3.8 prepared as Example 1 were prepared. , Each stored at 60 ° C. for 2 weeks.
The amount of TTFD after storage at 60 ° C. for 2 weeks was measured, and the 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 after storage at 60 ° C. for 2 weeks under harsh conditions.

[Test Example 2] Water separation of gel-like composition After storing each gel-like composition at 50 ° C. and 4 ° C. (control) for 8 weeks, the amount of water separation is measured by the measurement method described later, and then the water separation rate is calculated. From this, the difference of [(water separation rate after storage at 50 ° C. for 8 weeks)-(water separation rate after storage at 4 ° C. for 8 weeks)] was calculated.
The difference in the water separation rate is shown in Table 3.

<Measuring method of water separation of gel-like composition>
In the measuring method, a mesh having a mesh opening of 2 mm [17th revision Japanese Pharmacopoeia, sieve number 8.6 (2000 μm)] and a sieve having a diameter of 200 mm were used as a sieve. After the gelled composition to be tested is placed in a container and exposed to predetermined storage conditions, the entire contents of the container are placed on a sieve under a sieve, the mass is measured, and the mass is A ( g).
After tilting the sieve by 45 degrees and holding it for 1 minute, the mass of the liquid (water separation) that fell from the sieve under the sieve was measured, and this was defined as B (g), and the water separation rate was calculated by the following formula.
Water separation rate (%) = B (g) / A (g) x 100

From the results shown in Table 3, in the gel-like composition of the present invention, water separation was highly suppressed at any pH.

[Test Example 3] Hardness of gel-like composition The hardness of each gel-like 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) was measured. ° C./control) was calculated and shown in Table 4.

<Test method for hardness of gel-like composition>
For this test, as a material tester, the material tester EZ-SX (product name, Shimadzu Corporation) (load cell: 50N, test jig: universal design hood test) that can measure the compressive stress of a substance by linear motion. Set, software: TRAPEZIUM X texture, thermostat: cold thermostat) was used.
The sample was filled in a container (diameter 40 mm, height 20 mm) up to a height of 15 mm, and using the material tester, a resin circular plunger (diameter 20 mm, height 8 mm) was used to compress the sample at a compression rate of 10 mm / sec. 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 placing the gel in a constant temperature bath at 20 ° C. and stabilizing it at 20 ° C.
The maximum value of the compressive stress in the two compressions was taken as the hardness of the sample.

For the gel-like composition, the hardness [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 ratio is shown in Table 4.
In the table, "ND" indicates that no gel-like 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 maintained at all or almost no.

From the results shown in Table 4, the oral gel composition of the present invention was appropriately stored at 50 ° C. for 8 weeks under harsh conditions at any pH as compared with the gel composition of the comparative example. High hardness was maintained.

Formulation Example 1
According to the formulation of Table 5, vitamin _{B 1} class (fursultiamine hydrochloride), and 1.5 g / L gellan gum (deacylated (LA) gellan gum, San-Ei Gen Efuefu eye) containing vitamin _{B 1} class 1 mass An oral gel-like composition (pH adjusted to 3.1) containing 100 parts by mass of gellan gum was prepared.

According to the present invention, vitamin B ₁ and gellan gum are contained, and vitamin B ₁ is contained in the range of 10 to 2000 parts by mass with respect to 1 part by mass of vitamin B _1. An oral gel-like composition that stably contains the above species and has a stable gel-like form is provided.

Claims (5)

An oral gel-like composition containing vitamin B ₁ and gellan gum, and containing gellan gum in the range of 10 to 2000 parts by mass with respect to 1 part by mass of vitamin B ₁ . An oral gel-like composition containing vitamin B ₁ and gellan gum and having a gellan gum content of less than 3.0 g / L. An oral gel-like composition containing vitamin B ₁ and gellan gum and having a pH in the range of 2.5 to 3.8. The oral gel composition according to any one of claims 1 to 3, which is used as a pharmaceutical product or a quasi drug. Vitamin B ₁ is thiamine hydrochloride, thiamine nitrate, bistiamine nitrate, thiamine disulfide, thiamine disetyl sulfate, disetiamine hydrochloride, flusultiamine, flusultiamine hydrochloride, octothiamine, sicothamine, bisibuchiamine, bis. The oral gel composition according to any one of claims 1 to 4, which is one or more selected from the group consisting of bentiamine, prosultiamine, and benfothiamine.