JP2024050456A - Vitamin B1-containing oral composition - Google Patents

Abstract

[Problem] To provide an oral composition containing vitamin B1 or its derivatives or salts thereof, in which the unpleasant odor derived from vitamin B1 is reduced. [Solution] An oral composition characterized by containing vitamin B1 and pumpkin seed extract, in which the concentration of vitamin B1 is the following i) or ii): i) 0.0001 w/v% to 2.0 w/v% in the case of an oral liquid composition, ii) 0.0001 w/w% to 2.0 w/w% in the case of an oral solid composition [Selected Figure] None

Description

The present invention relates to an oral composition containing vitamin B1 or a derivative thereof, or a salt thereof. More specifically, the present invention relates to an oral composition in which the unpleasant odor derived from vitamin B1 or a derivative thereof, or a salt thereof is reduced.

Vitamin B1 or its derivatives or salts thereof (hereinafter referred to as "vitamin B1 type") are known as nutrients necessary for maintaining bodily functions, and a deficiency can cause symptoms of beriberi and central nervous system disorders, so they must be taken from medicines, quasi-drugs and foods. Vitamin B1 is incorporated into many products, such as vitamin-containing health supplements taken for nutritional supplementation during physical fatigue, and soft drinks that provide a day's worth of nutrients, and contributes to nutritional supplementation for the general public. However, vitamin B1 type is known to produce a distinctive unpleasant odor similar to rotten eggs, making it difficult to develop a product that is easy to take from the standpoint of flavor.

To solve these problems, a method is known in which limonene and nootkatone, which are often found in citrus fruits, are added to suppress the unpleasant odor specific to vitamin B1 (Patent Document 1). In addition, a method is also known in which black tea extract is added to an acidic drinkable composition containing vitamin B1 to prevent the generation of unpleasant odor components due to the decomposition of vitamin B1 (Patent Document 2). However, in either case, the flavor of the product is limited, making it less versatile, and further technological improvements were required.

Patent No. 5371827 Patent No. 4418702

The present invention provides an oral composition containing vitamin B1 or its derivatives or salts thereof, in which the unpleasant odor derived from vitamin B1 is reduced.

As a result of extensive research aimed at solving the above problems, the inventors have discovered that the unpleasant odor caused by vitamin B1 can be reduced by incorporating a seed extract of Cucurbita pepo L. var. Steirica, a plant of the Cucurbitaceae family in a composition containing vitamin B1.
That is, the present invention is as follows.
(1) An oral composition comprising vitamin B1 and a pumpkin seed extract, the concentration of vitamin B1 being the following i) or ii):
i) 0.0001 w/v% to 2.0 w/v% for oral liquid compositions
ii) 0.0001 w/w% to 2.0 w/w% for oral solid compositions
(2) The oral composition according to (1), wherein the vitamin B1 group is at least one selected from the group consisting of thiamine, fursultiamine, thiamine disulfide, benfotiamine, and salts thereof.
(3) The oral composition according to (1) or (2), wherein the concentration of the pumpkin seed extract is the following i) or ii):
i) 0.01 w/v% to 2.0 w/v% for oral liquid compositions
ii) 0.01 w/w% to 20.0 w/w% for oral solid compositions
(4) The oral composition according to any one of (1) to (3), wherein the concentration of enterodiol is the following i) or ii):
i) 0.0002 w/v% to 0.08 w/v% for oral liquid compositions
ii) 0.0002 w/w% to 0.8 w/w% for oral solid compositions
(5) The oral composition according to any one of (1) to (4), wherein the concentration of adenosine is the following i) or ii):
i) 0.00001 w/v% to 0.004 w/v% for oral liquid compositions
ii) 0.00001 w/w% to 0.04 w/w% for oral solid compositions
(6) The oral composition according to any one of (1) to (5), which is an oral liquid composition or an oral solid composition.
(7) The oral liquid composition according to any one of (1) to (6), having a pH of 2.0 to 7.0.
(8) A method for suppressing the unpleasant odor of vitamin B1 in a vitamin B1-containing oral composition by adding a pumpkin seed extract.
(9) An unpleasant odor suppressant for vitamin B1 containing pumpkin seed extract as an active ingredient.

The present invention makes it possible to provide an oral composition containing vitamin B1 that reduces the unpleasant odor caused by vitamin B1.

In the present invention, vitamin B1 refers to vitamin B1 or its derivatives or salts, which are usually edible, and examples thereof include thiamine, dicethiamine, fursultiamine, thiamine disulfide, bisbentiamine, bis-ibuthiamine, benfotiamine, shikotiamine, octotiamine, prosultiamine, and salts thereof. Among vitamin B1, preferred are thiamine, dicethiamine, fursultiamine, thiamine disulfide, benfotiamine, and salts thereof, and more preferred are thiamine, fursultiamine, and benfotiamine. Furthermore, examples of salts used in the present invention include nitrates, hydrochlorides, sulfates, and the like, and preferably nitrates or hydrochlorides.

The content of vitamin B1 in the oral liquid composition of the present invention is usually 0.0001 w/v% to 2.0 w/v%, preferably 0.0001 w/v% to 0.1 w/v%, and more preferably 0.0005 w/v% to 0.02 w/v%, and in the oral solid composition of the present invention, it is usually 0.0001 w/w% to 2.0 w/w%, preferably 0.01 w/w% to 1.5 w/w%, and more preferably 0.01 w/w% to 1.0 w/w%.

The Cucurbita pepo seed extract of the present invention is obtained by extracting the seeds of Cucurbita pepo L. var. Steirica, a plant of the Cucurbitaceae family, either as is or, if necessary, after drying, crushing, grinding, etc.

The extraction method is not particularly limited, and may be performed by known extraction methods such as stirring, shaking, and immersion extraction using an organic solvent such as ethanol, water, or a mixture thereof, or reduced pressure steam distillation extraction. If necessary, insoluble matter may be removed by centrifugation, enzyme treatment (treatment with an enzyme agent based on Aspergillus oryzae, Aspergillus niger, etc.), column or filtration (filtration with a strainer mesh, membrane filter, etc.). In the present invention, the pumpkin seed extract is preferably extracted using water and/or alcohol as the extraction solvent, more preferably ethanol as the alcohol, and particularly preferably water alone.

The extract obtained by the above extraction may be used in liquid form, or may be dried into a powder form, or a commercially available product sold in powder form (e.g., Western pumpkin seed dried extract GMP365 manufactured by Ask Pharmaceutical Co., Ltd.) may be used.

The content of Cucurbita pepo seed extract in the oral liquid composition of the present invention is preferably 0.01 w/v% to 2.0 w/v%, more preferably 0.1 w/v% to 1.0 w/v%, and in the oral solid composition of the present invention, it is usually 0.01 w/w% to 20.0 w/w%, preferably 0.01 w/w% to 10.0 w/w%, more preferably 0.1 w/w% to 5.0 w/w%.

Cucurbita pepo seed extract contains enterodiol and adenosine, and the amounts of enterodiol and adenosine can be measured by known methods using a spectrophotometer (UV) or high performance liquid chromatography (HPLC), etc.

In addition, the content of Cucurbita pepo seed extract in the present invention is preferably 2 to 10,000 parts by mass, more preferably 10 to 5,000 parts by mass, per part by mass of vitamin B1 when the present invention is an oral liquid composition, and is preferably 0.5 to 50 parts by mass, more preferably 2.5 to 25 parts by mass, per part by mass of vitamin B1 when the present invention is an oral solid composition.

The amount of enterodiol in the oral liquid composition of the present invention is preferably 0.0002 w/v% to 0.08 w/v%, more preferably 0.001 w/v% to 0.06 w/v%, and even more preferably 0.002 w/v% to 0.04 w/v%, and in the oral solid composition of the present invention, it is preferably 0.0002 w/w% to 0.8 w/w%, more preferably 0.0002 w/w% to 0.4 w/w%, and even more preferably 0.002 w/w% to 0.2 w/w%.

The amount of adenosine in the oral liquid composition of the present invention is preferably 0.00001 w/v% or more, more preferably 0.00001 w/v% to 0.004 w/v%, and even more preferably 0.0001 w/v% to 0.002 w/v%, and in the oral solid composition of the present invention, it is preferably 0.00001 w/v% or more, 0.00001 w/w% to 0.04 w/w%, and even more preferably 0.00001 w/w% to 0.02 w/w%.

The content of Cucurbita pepo seed extract in the oral composition of the present invention per one dose is preferably 100 mg to 2000 mg, more preferably 500 mg to 1000 mg, of Cucurbita pepo seed extract in the oral composition of the present invention. "Amount of oral intake per one dose" refers to the amount of the oral composition of the present invention taken at one time, more specifically, the amount taken intermittently or continuously within a period of, for example, 30 minutes, for example, 50 mL to 500 mL for an oral liquid composition, and 1 g to 30 g for an oral solid composition.

The pH of the oral composition of the present invention is not particularly limited, but for example, in the case of an oral liquid composition, from the viewpoint of suppressing the unpleasant odor of vitamin B1, it is preferably 2.0 to 7.0, more preferably 2.0 to 5.0, even more preferably 2.0 to 4.0, and particularly preferably 2.0 to 3.5.

The pH of the oral composition of the present invention can be adjusted using a commonly used pH adjuster. Specific pH adjusters include organic acids such as citric acid, malic acid, tartaric acid, succinic acid, lactic acid, acetic acid, maleic acid, gluconic acid, aspartic acid, adipic acid, glutamic acid, and fumaric acid, and their salts, inorganic acids such as phosphoric acid and hydrochloric acid, and inorganic bases such as sodium hydroxide, and preferred pH adjusters are citric acid, salts of citric acid, malic acid, salts of malic acid, hydrochloric acid, and sodium hydroxide.

In addition, the oral composition of the present invention may contain other ingredients such as vitamins (excluding vitamin B1), minerals, amino acids or salts thereof, herbal medicines, herbal extracts, royal jelly, caffeine, etc., as appropriate, within the scope of not impairing the effects of the present invention.

Additionally, the oral composition of the present invention may contain additives such as antioxidants, colorants, flavorings, flavorings, surfactants, thickeners, stabilizers, preservatives, sweeteners, and acidulants, as appropriate, within the scope of not impairing the effects of the present invention.

The oral composition in the present invention is not particularly limited as long as it is a composition that can be taken orally, and examples of such compositions include medicines, quasi-drugs, and foods (including functional foods, foods with nutritional claims, and foods for specified health uses).

The form of the oral composition of the present invention is not particularly limited, and may be liquid or solid, and is preferably liquid.For example, the oral liquid composition may be oral liquid, drink, soft drink, carbonated drink, sports/functional drink, non-alcoholic drink, milk drink, tea drink, coffee drink, fruit/vegetable drink, jelly drink, etc., and is preferably soft drink, carbonated drink, jelly drink.
For example, oral solid compositions include tablets such as chewable tablets, capsules, granules, microgranules, powders, etc., and from the viewpoint of being sufficiently effective in addressing the issue of unpleasant odors, tablets, granules, microgranules, and powders are preferred.

The oral composition of the present invention can be produced by a conventional method. For example, in the case of an oral liquid composition, each component is usually weighed, dissolved or dispersed in water, and water is further added to adjust the volume. If necessary, the pH is adjusted or heat sterilized, and the composition is filled into a container to provide an oral liquid composition that is easy to carry, that is, a container-packed oral liquid composition.
For example, an oral solid composition is usually obtained by weighing out each component, mixing, granulating, tableting, etc. The mixing method can be a commonly used method without any particular limitation, and may simply be mixed, or may be granulated after mixing. The granulation method can be a commonly used method without any particular limitation, and may be granulated by, for example, wet granulation method or dry granulation method. The tableting method can be a commonly used method without any particular limitation, and may be tableted after mixing each component, or tableted after granulation. In addition, the oral solid composition can be packaged and provided in an appropriate form, such as containers such as glass bottles and plastic containers, SP packaging, stick packaging, PTP packaging, and bags such as aluminum bags and paper bags.

The unpleasant odor suppressant of the present invention contains pumpkin seed extract as an active ingredient, and the content of the ingredients is the same as that described in the oral composition. In addition, the content of ingredients such as vitamin B1 and pumpkin seed extract in the unpleasant odor suppressant may be the same as that in the oral composition.

The present invention will be described in more detail below with examples and comparative examples, but the present invention is not limited to these examples. The vitamin B1 group was commercially available products such as thiamine nitrate manufactured by DSM Co., Ltd., thiamine hydrochloride manufactured by DSM Co., Ltd., fursultiamine hydrochloride manufactured by Watanabe Chemical Co., Ltd., and thiamine disulfide manufactured by Tokyo Chemical Industry Co., Ltd., the pumpkin seed extract was Western pumpkin seed dry extract GMP365 manufactured by Ask Pharmaceutical Co., Ltd., the granulated sugar was manufactured by DM Mitsui Sugar Co., Ltd., the citric acid (anhydrous) was manufactured by Iwata Chemical Co., Ltd., the trisodium citrate (crystalline) was manufactured by Showa Kako Co., Ltd., the crystalline cellulose was Ceolas PH-101 manufactured by Asahi Kasei Co., Ltd., and the 1 mol/L hydrochloric acid was manufactured by Fujifilm Wako Pure Chemical Co., Ltd. The pumpkin seed dry extract GMP365 used as the pumpkin seed extract contained 3% enterodiol and 0.192% adenosine.

Preparation of oral liquid composition:
Oral liquid compositions having the formulations shown in Tables 1 to 3 below were prepared according to the following method. First, a 0.1 w/v% solution of thiamine nitrate was prepared. Next, various concentrations of pumpkin seed dry extract GMP365 and thiamine nitrate 0.1 w/v% solution were added to 40% of the total amount of purified water, and thoroughly stirred. Then, purified water was added up to 96% of the total amount, and pH was adjusted using 1 mol/L hydrochloric acid as necessary, and the volume was adjusted to the full amount. Then, 40 ml of the mixture was filled into a screw tube No. 7 manufactured by Maruemu Co., Ltd., and sterilized at 80°C for 25 minutes to obtain oral liquid compositions (Examples 1 to 11). Oral liquid compositions not containing pumpkin seed dry extract GMP365 were used as comparative examples (Comparative Examples 1 to 8). Then, the prepared oral liquid compositions were stored in a constant temperature and humidity bath at 65°C (humidity fluctuation) for 7 days.

Oral liquid compositions having the formulations shown in Table 4 below were prepared according to the following method. Pumpkin seed dry extract GMP365, thiamine hydrochloride, fursultiamine hydrochloride, and thiamine disulfide were added to 40% of the total amount of purified water to obtain various concentrations, and thoroughly stirred. Purified water was then added up to 96% of the total amount, and the pH was adjusted using 1 mol/L hydrochloric acid as necessary, and the volume was adjusted to the full amount. Then, 40 ml was filled into a screw tube No. 7 manufactured by Maruemu Co., Ltd., and sterilized at 80°C for 25 minutes to obtain oral liquid compositions (Examples 12 to 14). Oral liquid compositions not containing pumpkin seed dry extract GMP365 were used as comparative examples (Comparative Examples 9 to 11). The prepared oral liquid compositions were then stored in a constant temperature and humidity chamber at 65°C (humidity fluctuation) for 7 days.

The oral liquid compositions having the formulations shown in Table 5 below were prepared according to the following method. First, pumpkin seed dry extract GMP365, granulated sugar, citric acid (anhydrous), and thiamine nitrate were added to 40% of the total amount of purified water to obtain various concentrations, and thoroughly stirred. Then, purified water was added to 96% of the total amount, and the pH was adjusted using trisodium citrate (crystal) as necessary, and the volume was adjusted to the full amount. Then, 40 ml was filled into a screw tube No. 7 manufactured by Maruemu Co., Ltd., and sterilized at 80°C for 25 minutes to obtain an oral liquid composition (Example 15). An oral liquid composition not containing pumpkin seed dry extract GMP365 was used as a comparative example (Comparative Example 12). The prepared oral liquid composition was then stored in a constant temperature and humidity bath at 65°C (humidity fluctuation) for 7 days.

Preparation of oral solid compositions:
The oral solid composition of the formulation shown in Table 6 below was prepared according to the following method. Western pumpkin seed dry extract GMP365, thiamine nitrate, and crystalline cellulose were weighed and mixed, and an appropriate amount of water was added and mixed, and 10 g was filled into a screw tube No. 7 manufactured by Maruemu Co., Ltd. to obtain an oral solid composition (Example 16). An oral solid composition without Western pumpkin seed dry extract GMP365 was used as a comparative example (Comparative Example 13). Then, the prepared oral solid composition was stored in a constant temperature and humidity chamber at 65°C (humidity fluctuation) for 7 days.

Unpleasant odor rating:
As described above, the odor of the oral composition stored at 65°C (at varying humidity) for 7 days was directly smelled from the screw tube by two well-trained testers, and the unpleasant odor originating from vitamin B1 was evaluated according to the criteria in Table 7.

As shown in Tables 1 to 6, the composition containing vitamin B1 and pumpkin seed extract showed the effect of reducing the unpleasant odor caused by vitamin B1.

The present invention makes it possible to easily suppress the unpleasant odor that occurs when vitamin B1 is contained in an oral composition, and is therefore expected to provide oral compositions with excellent flavor and marketability in the fields of pharmaceuticals, quasi-drugs, and foods.

Claims (8)

An oral composition comprising vitamin B1 and pumpkin seed extract, wherein the concentration of vitamin B1 is the following i) or ii).
i) 0.0001 w/v% to 2.0 w/v% for oral liquid compositions
ii) 0.0001 w/w% to 2.0 w/w% for oral solid compositions The oral composition according to claim 1, wherein the vitamin B1 is at least one selected from the group consisting of thiamine, fursultiamine, thiamine disulfide, benfotiamine, and salts thereof. 3. An oral composition according to claim 1 or 2, wherein the concentration of pumpkin seed extract is i) or ii) below.
i) 0.01 w/v% to 2.0 w/v% for oral liquid compositions
ii) 0.01 w/w% to 20.0 w/w% for oral solid compositions 3. The oral composition according to claim 1 or 2, wherein the concentration of enterodiol is i) or ii) below.
i) 0.0002 w/v% to 0.08 w/v% for oral liquid compositions
ii) 0.0002 w/w% to 0.8 w/w% for oral solid compositions 3. The oral composition according to claim 1 or 2, wherein the concentration of adenosine is i) or ii) below.
i) 0.00001 w/v% to 0.004 w/v% for oral liquid compositions
ii) 0.00001 w/w% to 0.04 w/w% for oral solid compositions The oral composition according to claim 1 or 2, which is an oral liquid composition or an oral solid composition. The oral liquid composition according to claim 1 or 2, which has a pH of 2.0 to 7.0. A method for suppressing the unpleasant odor of vitamin B1 in an oral composition containing vitamin B1 by including pumpkin seed extract.