Composition, raw material composition of cosmetic, virus proliferation suppressing agent, use of composition for suppressing virus proliferation, method for suppressing virus proliferation, and sealed body

Abstract

Provided is a 2,3-BDO composition capable of appropriately exhibiting an effect of suppressing virus proliferation. A composition according to the present invention contains at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol, and does not contain (meso)-2,3-butanediol.

Description

Composition, cosmetic raw material composition, virus proliferation inhibitor, use of composition for inhibiting virus proliferation, method for inhibiting virus proliferation, and sealed body

[0001] The present invention relates to a composition, a raw material composition for cosmetics, a virus growth inhibitor, use of the composition for inhibiting virus growth, a method for inhibiting virus growth, and a sealed body.

[0002] 2,3-Butanediol (hereinafter also referred to as "2,3-BDO") is used, for example, as an antifreeze, and as a raw material for methyl ethyl ketone and 1,3-butadiene, which are produced by dehydration. －１ ) and ethanol (29055 kJ.kg －１ ) equivalent to a calorific value of 27,198 kJ. kg －１ It is a chemical with important potential industrial uses as a liquid fuel for pharmaceuticals. Other potential uses include the manufacture of printing inks, perfumes, cosmetic ingredients, fumigants, moisturizers and softeners, explosives and plasticizers, and as a carrier for pharmaceuticals.

[0003] Furthermore, in recent years, research has been conducted into the application of 2,3-BDO as an antibacterial and antiviral agent, and Patent Document 1 discloses an antiviral composition comprising 2,3-butanediol and an acid. This document discloses that 2,3-butanediol itself is an alcohol that cannot inactivate viruses. Furthermore, Patent Document 2 discloses an antibacterial agent comprising (meso)-2,3-butanediol, but does not mention its antiviral activity. Patent Documents 1 and 2 and Non-Patent Document 1 are incorporated herein.

[0004] Special table 2018-531991 publication Special table 2017-531671 publication

[0005] Bulletin of the Central Customs Laboratory, No. 20, 1980, pp. 123-127

[0006] Thus, 2,3-BDO has not previously been recognized as having antiviral activity, and its use as a drug for inhibiting viral proliferation has not been considered at all. An object of the present invention is to provide a 2,3-BDO composition that can appropriately exert a viral proliferation inhibitory effect in applications where 2,3-BDO is required to have such an effect.

[0007] The present inventors have conducted extensive research into why 2,3-BDO does not exhibit the viral proliferation inhibitory effect mentioned in Patent Document 1, and as a result have newly discovered that there is a correlation between the abundance ratio of optical isomers of 2,3-BDO and the viral inhibitory effect.

[0008] Generally, chemically synthesized products of 2,3-BDO contain three optical isomers: (2R,3R)-2,3-butanediol, (2S,3S)-2,3-butanediol, and (meso)-2,3-butanediol. Figure 4 is a gas chromatography chart showing the proportions of the optical isomers of 2,3-BDO in Non-Patent Document 1. As shown in FIG. 4, a typical chemically synthesized product of 2,3-BDO contains the optical isomers in a weight ratio of (2R,3R)-2,3-butanediol: (2S,3S)-2,3-butanediol: (meso)-2,3-butanediol = 1:1:4.25 (the peak at around 14 minutes is a peak containing both (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol (indicated by the initial letter r for the racemate in FIG. 4), and the peak at around 16 minutes is the peak for (meso)-2,3-butanediol (indicated by m in FIG. 4)).

[0009] The present inventors discovered that (meso)-2,3-butanediol promotes viral proliferation, while (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol inhibit viral proliferation, and arrived at the present invention. That is, the composition of the present invention is characterized by containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol, but not containing (meso)-2,3-butanediol.

[0010] As described above, (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol inhibit viral proliferation. Furthermore, the composition of the present invention contains 2,3-BDO and does not contain (meso)-2,3-butanediol, which promotes viral proliferation, and therefore has a high viral proliferation inhibitory effect.

[0011] The reason why typical chemically synthesized 2,3-BDO products are not recognized to have antiviral effects is thought to be that these chemically synthesized 2,3-BDO products contain both (meso)-2,3-butanediol, which promotes viral growth, and (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, which suppress viral growth, and as a result of these antagonisms, they are observed to have almost no antiviral effect.

[0012] In the present invention, the "viral proliferation inhibitory effect" is determined to be a viral proliferation inhibitory effect if administering the target composition reduces the viral proliferation ability compared to administering water.

[0013] The composition of the present invention contains the above-mentioned (2R,3R)-2,3-butanediol and the above-mentioned (2S,3S)-2,3-butanediol, and preferably has a weight ratio of (2R,3R)-2,3-butanediol / (2S,3S)-2,3-butanediol = 1 / 1000 to 1000 / 1. Alternatively, the weight ratio of (2R,3R)-2,3-butanediol content / (2S,3S)-2,3-butanediol content may be 1 / 100 to 100 / 1, or even (2R,3R)-2,3-butanediol content / (2S,3S)-2,3-butanediol content may be 1 / 10 to 10 / 1. Within this weight ratio range, the viral proliferation inhibitory effect is suitably exhibited.

[0014] The composition of the present invention is preferably used as a virus growth inhibitor. As described above, the composition of the present invention exhibits a virus growth inhibitory effect. Therefore, the composition of the present invention is suitable as a virus growth inhibitor.

[0015] The cosmetic raw material composition of the present invention is characterized by containing the above-mentioned composition of the present invention. As described above, the composition of the present invention exhibits a virus proliferation inhibitory effect. Therefore, when a cosmetic is produced from the cosmetic raw material composition containing the composition of the present invention, the cosmetic exhibits a virus inhibitory effect.

[0016] The virus growth inhibitor of the present invention is characterized by containing at least (2S,3S)-2,3-butanediol and not containing (meso)-2,3-butanediol. When (2S,3S)-2,3-butanediol is compared with (2R,3R)-2,3-butanediol, (2S,3S)-2,3-butanediol exhibits a stronger virus growth inhibitory effect. Because the virus growth inhibitor of the present invention contains (2S,3S)-2,3-butanediol and does not contain (meso)-2,3-butanediol, which promotes virus growth, the virus growth inhibitory effect is more suitably exhibited.

[0017] The virus proliferation inhibitor of the present invention is characterized by containing at least (2R,3R)-2,3-butanediol but not containing (meso)-2,3-butanediol. While (2R,3R)-2,3-butanediol is colorless and transparent, (2S,3S)-2,3-butanediol is slightly yellow in color. Therefore, from the viewpoint of freedom in color adjustment, it is preferable to contain (2R,3R)-2,3-butanediol but not contain (meso)-2,3-butanediol.

[0018] The use of the present invention is the use of a composition containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol for inhibiting viral proliferation.

[0019] A composition containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol exhibits a virus proliferation inhibitory effect, and therefore, the use of the composition of the present invention is suitable for inhibiting virus proliferation.

[0020] The method for inhibiting viral proliferation of the present invention is characterized by comprising a step of contacting a virus with a composition that contains at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and does not contain (meso)-2,3-butanediol.

[0021] In the method for inhibiting viral proliferation of the present invention, a composition containing (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol, which inhibits viral proliferation, but not containing (meso)-2,3-butanediol, which promotes viral proliferation, is brought into contact with a virus. This reduces the viral proliferation ability. Therefore, the method of the present invention can inhibit viral proliferation.

[0022] The sealed body of the present invention comprises: a composition containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol; a container having a storage section for storing the composition and an opening for the composition to enter and exit; and a sealing member disposed on the container so as to close the opening, wherein the storage section has a space in which the composition is not present, and the space is filled with an inert gas or air having a humidity of 10% or less.

[0023] Compositions containing (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not (meso)-2,3-butanediol are highly hygroscopic, and when moisture is present around the composition, they absorb the moisture, causing the (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol to oxidize and easily decompose into peroxides. However, the container portion of the sealed body of the present invention has a space where the composition is not present, and this space is filled with an inert gas or air with a humidity of 10% or less. Therefore, such decomposition is less likely to occur.

[0024] In the sealed product of the present invention, the composition may contain the (2R,3R)-2,3-butanediol and the (2S,3S)-2,3-butanediol, and the weight ratio of (2R,3R)-2,3-butanediol / (2S,3S)-2,3-butanediol may be 1 / 1000 to 1000 / 1. When the weight ratio is within this range, the composition preferably exhibits its effect of inhibiting viral proliferation.

[0025] In the sealed product of the present invention, the composition may be used as a virus growth inhibitor. A composition containing (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol exhibits a virus growth inhibitory effect. Therefore, the composition is suitable as a virus growth inhibitor. Furthermore, as described above, the composition is not easily denatured.

[0026] In the sealed body of the present invention, the container may contain a cosmetic raw material composition containing the composition. A composition containing (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol exhibits a virus growth inhibitory effect. Therefore, when cosmetics are produced from a cosmetic raw material composition containing the composition, the cosmetics exhibit a virus inhibitory effect. Furthermore, as described above, the composition is not easily denatured.

[0027] According to the present invention, a composition capable of appropriately exhibiting the effect of inhibiting viral proliferation can be provided.

[0028] Fig. 1 is a cross-sectional view schematically showing an example of a sealed body of the present invention. Fig. 2 is a chart showing the results of GC-MS analysis of a composition according to Test Example 1. Fig. 3 is a chart showing the results of GC-MS analysis of a composition according to Example 5. Fig. 4 is a gas chromatography chart showing the proportions of optical isomers of 2,3-BDO in Non-Patent Document 1.

[0029] (Detailed Description of the Invention) The present invention is a 2,3-butanediol composition characterized by containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and not containing (meso)-2,3-butanediol.

[0030] (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol have excellent viral growth inhibitory effects, but conversely, (meso)-2,3-butanediol promotes viral growth. Commercially available 2,3-BDO contains these three optical isomers, and therefore exhibits almost no viral growth inhibitory effect. However, the composition of the present invention does not contain (meso)-2,3-butanediol, but contains (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, and therefore can exhibit a high viral growth inhibitory effect.

[0031] The composition of the present invention exhibits a viral proliferation inhibitory effect against enveloped and non-enveloped viruses.

[0032] The composition of the present invention preferably contains the above-mentioned (2R,3R)-2,3-butanediol and the above-mentioned (2S,3S)-2,3-butanediol, and the weight ratio of (2R,3R)-2,3-butanediol / (2S,3S)-2,3-butanediol is 1 / 1000 to 1000 / 1. When the weight ratio is within this range, the viral proliferation inhibitory effect is suitably exhibited.

[0033] The viral growth inhibitory effect of (2S,3S)-2,3-butanediol is greater than that of (2R,3R)-2,3-butanediol, and therefore, in the composition of the present invention, the content of (2S,3S)-2,3-butanediol is preferably greater than the content of (2R,3R)-2,3-butanediol, and more preferably, the composition contains only (2S,3S)-2,3-butanediol. Such a composition is suitable as a viral growth inhibitor.

[0034] Furthermore, while (2R,3R)-2,3-butanediol is colorless and transparent, (2S,3S)-2,3-butanediol is slightly yellow in color. Therefore, in the composition of the present invention, it is preferable that the content of (2R,3R)-2,3-butanediol is greater than the content of (2S,3S)-2,3-butanediol from the viewpoint of freedom in color adjustment, and it is more preferable that the composition contains only (2R,3R)-2,3-butanediol. In particular, when the composition of the present invention is used as a cosmetic raw material, it is advantageous because freedom in color adjustment of cosmetics can be ensured.

[0035] In the composition of the present invention, the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol is preferably 5 to 100% by weight based on the weight of the entire composition.

[0036] When the composition of the present invention does not contain either (2R,3R)-2,3-butanediol or (2S,3S)-2,3-butanediol, the term "total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol" means the content of either (2R,3R)-2,3-butanediol or (2S,3S)-2,3-butanediol contained in the composition.

[0037] The composition of the present invention can be used without any particular limitation as long as it is used as a virus growth inhibitor that can exhibit a virus growth inhibitory effect. Specifically, the composition of the present invention can be used as a skin care topical composition, cosmetic composition, pharmaceutical composition, food additive, etc. Furthermore, the composition of the present invention can be formulated, for example, in the form of makeup cosmetics, toner, cream, lotion, essence, pack, etc., more specifically, in the form of softening toner, astringent toner, nutritious toner, eye cream, nutritious cream, massage cream, cleansing cream, cleansing foam, cleansing water, powder, foundation, makeup base, essence, pack, etc., and the formulation is not particularly limited. Furthermore, in each formulation, other ingredients can be appropriately selected and blended by those skilled in the art without difficulty depending on the type of other composition or the intended use. Furthermore, the composition of the present invention can be preferably formulated as a cleanser composition, and the formulation is not particularly limited, but specifically, it can be formulated in the form of a hand disinfectant, hand wash, body wash, cleansing cream, cleansing gel, cleansing foam, cleansing water, soap, wet tissue, etc.

[0038] The cosmetic raw material composition of the present invention is characterized by containing the above-mentioned composition of the present invention. As described above, the composition of the present invention exhibits a virus proliferation inhibitory effect. Therefore, when a cosmetic is produced from the cosmetic raw material composition containing the composition of the present invention, the cosmetic exhibits a virus inhibitory effect.

[0039] The virus growth inhibitor of the present invention is characterized by containing at least (2S,3S)-2,3-butanediol and not containing (meso)-2,3-butanediol. When (2S,3S)-2,3-butanediol is compared with (2R,3R)-2,3-butanediol, (2S,3S)-2,3-butanediol exhibits a stronger virus growth inhibitory effect. Because the virus growth inhibitor of the present invention contains (2S,3S)-2,3-butanediol and does not contain (meso)-2,3-butanediol, which promotes virus growth, the virus growth inhibitory effect is more suitably exhibited.

[0040] The virus growth inhibitor of the present invention is characterized by containing at least (2R,3R)-2,3-butanediol and not containing (meso)-2,3-butanediol. The virus growth inhibitor of the present invention contains (2R,3R)-2,3-butanediol and does not contain (meso)-2,3-butanediol, which promotes virus growth, and therefore exhibits a more favorable virus growth inhibitory effect. Furthermore, while (2R,3R)-2,3-butanediol is colorless and transparent, (2S,3S)-2,3-butanediol is slightly yellow in color. Therefore, the composition of the present invention is advantageous in terms of the degree of freedom in color adjustment.

[0041] Next, a method for producing the composition of the present invention will be described. The composition of the present invention can be prepared by mixing industrially produced (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol, and (2S,3S)-2,3-butanediol in a predetermined ratio. Furthermore, optical isomers of 2,3-BDO can also be produced using microorganisms, as described, for example, in JP-A-10-234390 (Bacillus bacteria), JP-A-2015-518736 (genetically modified Escherichia coli), and JP-A-2004-357639 (genetically modified Escherichia coli). (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol are commercially available, specifically, (2R,3R)-2,3-butanediol (manufactured by Tokyo Chemical Industry Co., Ltd. (TCI) product number B1161) and (2S,3S)-2,3-butanediol (manufactured by Tokyo Chemical Industry Co., Ltd. (TCI) product number B1343), respectively. JP-A Nos. 10-234390, 2015-518736, and 2004-357639 are incorporated herein by reference.

[0042] (Method for measuring the proportion of optical isomers of 2,3-BDO in a composition) In the composition of the present invention, the proportions of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol can be quantitatively and qualitatively analyzed using gas chromatography mass spectrometry (GC-MS) analysis and a chiral column. Quantitative and qualitative analysis is also possible when the composition contains (meso)-2,3-butanediol in addition to (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol. Agilent Technologies, Inc. possesses technology for separating the three optical isomers of 2,3-BDO, and the three optical isomers of 2,3-BDO can be separated, for example, under the following analytical conditions. Quantitative analysis is also possible by creating a calibration curve using standard samples of each optical isomer.

[0043] Apparatus: GC / MS: Agilent Technologies 7890A / 5975C Measurement conditions Column: CP-Chirasil, 25 m x 0.25 mm id x 0.25 μm film thickness (Agilent Technologies, Inc.) Column temperature: 80°C (5 min) → +2°C / min → 150°C Column pressure: 51.5 kPa (constant linear flow rate mode) Carrier gas: He (1.0 mL / min) Injection port: 200°C, split 10:1 Injection volume: 1 μL Detector: MS Ionization method: EI method Electron energy: 70 eV EM voltage: 1294 V Ion source temperature: 230°C Interface temperature: 200°C Mass range: m / z=10-800

[0044] As used herein, "the composition does not contain (meso)-2,3-butanediol" means that when the composition is subjected to GC-MS analysis under the above conditions, there is no peak with an S / N ratio of 3 or more at the position where (meso)-2,3-butanediol is detected (around 14 minutes in each Example and Comparative Example). The position where (meso)-2,3-butanediol is detected can be determined using a standard sample.

[0045] Use of the composition of the present invention for inhibiting viral proliferation is one aspect of the present invention. That is, use of a composition containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol for inhibiting viral proliferation is the use of the present invention.

[0046] A composition containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol exhibits a virus proliferation inhibitory effect, and therefore, the use of the composition of the present invention is suitable for inhibiting virus proliferation.

[0047] The method for inhibiting viral proliferation of the present invention is characterized by comprising a step of contacting a virus with a composition that contains at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and does not contain (meso)-2,3-butanediol.

[0048] In the method for inhibiting viral proliferation of the present invention, a composition containing (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol, which inhibits viral proliferation, but not containing (meso)-2,3-butanediol, which promotes viral proliferation, is brought into contact with a virus. This reduces the viral proliferation ability. Therefore, the method of the present invention can inhibit viral proliferation.

[0049] The method for contacting the composition with viruses is not particularly limited. For example, to suppress the proliferation of viruses attached to a substrate, the composition may be sprayed onto the substrate to bring the composition into contact with the viruses, or a cloth may be impregnated with the composition and used to wipe the surface of the substrate, the human body, or the like with the cloth to bring the composition into contact with the viruses.

[0050] The sealed product of the present invention comprises a composition comprising at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but no (meso)-2,3-butanediol; a container having a storage section for storing the composition and an opening for the composition to enter and exit; and a sealing member disposed on the container so as to close the opening, wherein the storage section has a space free of the composition, and the space is filled with an inert gas or air having a humidity of 10% or less.

[0051] A composition containing (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol is highly hygroscopic, and when moisture is present around the composition, the composition absorbs the moisture, causing the (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol to oxidize and easily decompose into peroxides. However, the container portion of the sealed body of the present invention has a space where the composition is not present, and this space is filled with an inert gas or air with a humidity of 10% or less (including 0%), so such decomposition is unlikely to occur.

[0052] The material of the container constituting the sealed body of the present invention is not particularly limited as long as it is not corroded by 2,3-butanediol, and may be metal, glass, or the like. The shape of the container is also not limited, but a cylindrical container with a bottom is preferred. In such a cylindrical container, the top surface serves as an opening for introducing and removing the composition. In the sealed body of the present invention, a sealing member is disposed to close the opening. The shape of the sealing member may be lid-shaped, stopper-shaped, or the like. Materials that can be used for the sealing member include metal, glass, fluororesin, and silicone resin. In the sealed body of the present invention, the sealing member may be in the form of a screw cap. That is, in the sealed body of the present invention, a spiral groove may be provided on the outer wall of the periphery of the opening of the container, and the sealing member may be in the form of a cap that covers the opening of the container. A spiral protrusion that fits into the spiral groove of the container may be provided on the inner wall of the cap-shaped sealing member in the area that comes into contact with the container. In this way, the cap-shaped sealing member may be fixed to the container by rotating the cap-shaped sealing member. In addition, in the sealed body of the present invention, a spiral convex portion may be provided on the outer wall of the periphery of the opening of the container, and a spiral groove may be provided on the inner wall of the cap-shaped sealing member in the area that comes into contact with the container.

[0053] In the sealed body of the present invention, the inert gas filled into the space may be nitrogen, argon, helium, carbon dioxide, etc. Furthermore, when filling the space with air having a humidity of 10% or less, the humidity of the air may be adjusted to 10% or less (preferably 0%, i.e., no moisture) by absorbing moisture with calcium chloride, silica gel, etc., and the humidified air may then be filled.

[0054] The composition contained in the container of the sealed body of the present invention is unlikely to be denatured within the sealed body, so it is preferable to store the sealed body of the present invention as is or transport it in the sealed state.

[0055] An example of such a sealed body of the present invention will be described with reference to the drawings. Fig. 1 is a cross-sectional view schematically showing an example of a sealed body of the present invention. The sealed body 1 shown in Fig. 1 comprises a composition 30, a container 11 having a storage section 11a for storing the composition 30 and an opening 11b through which the composition 30 can enter and exit, and a lid-like sealing member 12 disposed on the container 11 so as to close the opening 11b. The storage section 11a has a space 20 in which the composition 30 is not present.

[0056] The composition 30 contains at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol, but does not contain (meso)-2,3-butanediol.

[0057] The space 20 is filled with an inert gas or air with a humidity of 10% or less.

[0058] As shown in FIG. 1, two holes 13 are formed in the sealing member 12, and the two holes 13 are closed by two plug-like bodies 14.

[0059] The container 11a may be made of a cylindrical glass with a bottom, and the sealing member 12 may be made of a silicone resin.

[0060] When manufacturing the sealed body 1, the composition 30 is placed in the containing portion 11a, and the sealing member 12 is fitted into the opening 11b. At this time, the plug 14 of the sealing member 12 is removed from the hole 13 in advance.

[0061] Then, an inert gas such as nitrogen gas is poured in through one of the holes 13 to replace the air in the space with the inert gas, and then the two holes 13 are closed with two stoppers 14, thereby sealing the composition 30 in the container 11 containing the inert gas. In this way, the sealed body 1 of the present invention can be produced.

[0062] Instead of the inert gas, the air in space 20 may be replaced with air from which moisture has been sufficiently removed using calcium chloride or the like (humidity 10% or less). This sealed body 1 may be stored as is, or the sealed body 1 may be transported to another location and the composition 30 contained therein may be removed.

[0063] Test Example 1, Examples 1 to 5, and Comparative Examples 1 to 3 (meso)-2,3-butanediol (Sigma-Aldrich, product number 361461), (2R,3R)-2,3-butanediol (Tokyo Chemical Industry, product number B1161), (2S,3S)-2,3-butanediol (Tokyo Chemical Industry, product number B1343), and water (ion-exchanged water) were mixed in the weight ratios shown in Table 1 to prepare compositions according to Test Example 1 and Examples 1 to 5. In addition, a composition containing only water was prepared as Comparative Example 1, and a composition comprising a mixture of (meso)-2,3-butanediol and water was prepared as Comparative Example 2. Furthermore, Comparative Example 3 is a composition containing (2R,3R)-2,3-butanediol, (2S,3S)-2,3-butanediol, (meso)-2,3-butanediol, and water, with a weight ratio of (2R,3R)-2,3-butanediol:(2S,3S)-2,3-butanediol:(meso)-2,3-butanediol=1:1:4.25.

[0064] The composition according to Test Example 1 was subjected to GC-MS analysis as described above in "(Method for measuring the proportion of optical isomers of 2,3-BDO in a composition)." FIG. 2 is a chart showing the results of GC-MS analysis of the composition according to Test Example 1. As shown in FIG. 2, it was demonstrated that even if (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol, and (2S,3S)-2,3-butanediol were present in the composition, they could be separated. Furthermore, it was demonstrated that the weight percentages of the contents of (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol, and (2S,3S)-2,3-butanediol could also be calculated based on this chart.

[0065] The composition of Example 1 was subjected to GC-MS analysis as described above in "(Method for measuring the proportion of optical isomers of 2,3-BDO in a composition)." Figure 3 is a chart showing the results of GC-MS analysis of the composition of Example 5. As shown in Figure 3, it was confirmed that the composition of Example 5 does not have a peak with an S / N ratio of 3 or more at the position where (meso)-2,3-butanediol is detected (around 14 minutes).

[0066] (Measurement of Residual Phage Virus Count) Using the compositions according to each Example and Comparative Example, the virus proliferation inhibitory effect was measured by counting the residual phage virus count in accordance with JIS R 1756. (1) 10 g of tryptophan, 5 g of yeast extract, 10 g of sodium chloride, and 15 g of agar were mixed in 1 L of water and autoclaved at 120°C for 10 minutes. The solution was placed in a Petri dish (90 mmφ×15 mm) and cooled and solidified to prepare a 1.5% LB agar medium. (2) 300 μL of the composition according to each Example and Comparative Example and bacteriophage Qβ (10 ８ The mixture was mixed with 300 μL of (100 μL cpu / mL) and stirred three times by inversion, then allowed to stand at room temperature for 4 hours. (3) 200 μL of the solution (2) above was mixed with 9.8 mL of SCDLP solution. SCDLP solution was prepared by dissolving "Nutrient Broth" (manufactured by Wako Pure Chemical Industries, Ltd.) in water to a concentration of 41.8 g / L and autoclaving at 121°C, 2 atmospheres, and 20 minutes. (4) 1 mL of the solution (3) above was mixed into a test tube containing Escherichia coli (100 μL) in advance. (5) 4 mL of 0.5% LB agar solution (prepared by mixing 10 g tryptophan, 5 g yeast extract, 10 g sodium chloride, and 15 g agar with 1 L of water and maintaining at 45°C) was added to 1 mL of the solution (4) above, and the mixture was stirred once by inversion. (6) The solution from (5) above was placed in the LB agar medium dish from (1) above, and the solution from (5) above was spread over the surface of the agar medium while slowly rotating the dish. (7) Thereafter, the dish was left at 37°C for 16 hours. (8) The number of plaques that appeared in the dish was counted visually. The results are shown in Table 1.

[0067]

[0068] The plaques that appeared in the petri dish in step (8) above will now be described. By carrying out step (7) above, E. coli proliferates, forming a colony of E. coli over the entire surface of the LB agar medium in the petri dish. If active bacteriophage (virus) remains in the solution in step (5) above, the bacteriophage (virus) dissolves the E. coli cell membrane, causing the E. coli to disappear. In that area, no colony of E. coli forms, leaving only the LB agar medium. The area of ​​only the LB agar medium formed by the disappearance of E. coli is called a plaque, and the number of remaining bacteriophage (virus) can be counted by counting the number of plaques. A large number of such plaques indicates a large number of active bacteriophage (virus), while a small number of plaques indicates a small number of active bacteriophage (virus). In this experiment, a small number of plaques means that bacteriophage (virus) activity was inhibited by the compositions of the Examples and Comparative Examples in step (2). In other words, a small number of plaques observed means that the compositions used in step (2) have a high bacteriophage (virus) proliferation inhibitory effect.

[0069] (Antiviral Activity Evaluation Using Bacteriophage) To evaluate the viral proliferation inhibitory effect (hereinafter referred to as "antiviral activity") of the compositions according to Examples 1 to 5 and Comparative Examples 1 to 3, viral inactivation was measured using a modified version of the JIS R1756 antiviral activity test method for visible-light-responsive photocatalytic materials. Specifically, the compositions according to Examples 1 to 4, water (Comparative Example 1), and an aqueous (meso)-2,3-butanediol solution (Comparative Example 2) were mixed with bacteriophage Qβ in a sample tube, stirred by inversion, and then left for four hours to inactivate the bacteriophage (virus). The bacteriophage was then infected with Escherichia coli and left overnight, after which the number of bacteriophage (viruses) retaining their infectious capacity was measured. The measurement results, expressed as the concentration of bacteriophage (viruses) inactivated against Escherichia coli, were expressed as bacteriophage (virus) inactivation. Here, the concentration of bacteriophage (virus) inactivated against E. coli (bacteriophage (virus) inactivation degree) was used as an index of bacteriophage (virus) concentration, and the bacteriophage (virus) inactivation degree was calculated based on this bacteriophage (virus) inactivation degree.

[0070] The bacteriophage (virus) inactivation rate is the result of calculating the concentration of bacteriophage (virus) inactivated against E. coli by measuring the concentration of bacteriophage (virus) capable of infecting E. coli in an antiviral test using bacteriophage, using a bacteriophage Qβ concentration of 8.3 million / mL. In other words, the bacteriophage (virus) inactivation rate is the degree of concentration at which E. coli cannot be infected, relative to the bacteriophage Qβ concentration, and can be calculated by (bacteriophage Qβ concentration - concentration of virus capable of infecting E. coli) / (bacteriophage Qβ concentration) × 100.

[0071] The bacteriophage (virus) inactivation degree is calculated from this bacteriophage (virus) inactivation degree. The bacteriophage (virus) inactivation degree is a numerical value (represented as a negative value) expressed as common logarithm log(1-X), where the amount of the original bacteriophage (virus) is 1 and the relative amount of the bacteriophage (virus) inactivated after the bacteriophage (virus) inactivation treatment is X. The larger the absolute value, the higher the ability to inactivate the bacteriophage (virus). For example, if 99.9% of the original bacteriophage (virus) is inactivated, the bacteriophage (virus) inactivation degree is expressed as log(1-0.999) = -3.00. The bacteriophage (virus) inactivation rate is the ratio of the amount of bacteriophage (virus) inactivated after bacteriophage (virus) inactivation treatment to the total amount of bacteriophage (virus) before the bacteriophage (virus) inactivation treatment, expressed as a percentage (99.9% in the above case). As described above, the bacteriophage (virus) inactivation rate was calculated from the bacteriophage (virus) inactivation rate. The results are shown in Table 1.

[0072] The viral inactivation degree in the present invention is evaluated in accordance with JIS Z 2801 and JIS L 1922. The viral inactivation degree has an opposite sign to the antiviral activity value described below. According to JIS L 1922, an antiviral activity value of 2.0 or higher is considered to be antiviral, and an antiviral activity value of 3.0 or higher is considered to be sufficient (see JP 2018-177747 A, incorporated herein by reference).

[0073] The results in Table 1 show that in the case of a composition that did not contain (meso)-2,3-butanediol but contained (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, the number of plaques that appeared was almost zero, demonstrating a high viral growth inhibitory effect. Furthermore, the number of plaques in Comparative Example 2, which was a mixed composition of (meso)-2,3-butanediol and water, was greater than that in Comparative Example 1, which contained water, demonstrating that (meso)-2,3-butanediol has a viral growth inhibitory effect. Therefore, these test results also explain why 2,3-butanediol ((2R,3R)-2,3-butanediol:(2S,3S)-2,3-butanediol:(meso)-2,3-butanediol=1:1:4.25), which is industrially produced and sold as a reagent, does not exhibit any viral growth inhibitory effect.

[0074] The reason why viral proliferation is promoted or inhibited depending on the type of optical isomer of 2,3-BDO is predicted as follows. First, by comparing Comparative Example 1 and Comparative Example 2, it is predicted that (meso)-2,3-butanediol is a substance useful for viral proliferation and promotes the production of some substance biosynthesized during viral proliferation. On the other hand, (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol function as antagonists of (meso)-2,3-butanediol and inhibit the production of some substance biosynthesized during viral proliferation. In other words, it is predicted that the presence of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol prevents the production of some substance biosynthesized during viral proliferation, preventing the virus from proliferating, and as a result, the virus can be inactivated.

[0075] This can also be seen from Comparative Example 3. In Comparative Example 3, the content of (meso)-2,3-butanediol was 2.1 times the total content of the (2R,3R)-2,3-butanediol and the (2S,3S)-2,3-butanediol, and the virus proliferation inhibitory effect was lower than that of the water in Comparative Example 2, with the number of plaques being 55 and the virus inactivation rate being -1.15.

[0076] As described above, the composition of the present invention has an excellent effect of inhibiting viral proliferation, and can be used in applications where inhibition of such viral proliferation is required, such as as a raw material for cosmetics.

[0077] REFERENCE SIGNS LIST 1 Sealed body 11 Container 11a Storage portion 11b Opening 12 Sealing member 13 Hole 14 Plug-like body 20 Space 30 Composition

Claims

1. A composition comprising at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol, and not comprising (meso)-2,3-butanediol.

2. The composition according to claim 1, which contains the (2R,3R)-2,3-butanediol and the (2S,3S)-2,3-butanediol, and the weight ratio of (2R,3R)-2,3-butanediol / (2S,3S)-2,3-butanediol is 1 / 1000 to 1000 / 1.

3. The composition according to claim 1 or 2, which is used as an agent for inhibiting virus proliferation.

4. A cosmetic raw material composition comprising the composition according to claim 1 or 2.

5. A virus proliferation inhibitor comprising at least (2S,3S)-2,3-butanediol and no (meso)-2,3-butanediol.

6. A virus proliferation inhibitor comprising at least (2R,3R)-2,3-butanediol and no (meso)-2,3-butanediol.

7. Use of a composition containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol but not containing (meso)-2,3-butanediol for inhibiting viral proliferation.

8. A method for inhibiting viral proliferation, comprising a step of contacting a virus with a composition comprising at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and no (meso)-2,3-butanediol.

9. A sealed body comprising: a composition containing at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and not containing (meso)-2,3-butanediol; a container having a storage section for storing said composition and an opening for the composition to enter and exit; and a sealing member disposed on the container so as to close said opening, wherein the storage section has a space in which the composition is not present, and the space is filled with an inert gas or air having a humidity of 10% or less.

10. The sealed body according to claim 9, wherein the composition contains the (2R,3R)-2,3-butanediol and the (2S,3S)-2,3-butanediol, and the weight ratio of (2R,3R)-2,3-butanediol / (2S,3S)-2,3-butanediol is 1 / 1000 to 1000 / 1.

11. The sealed body according to claim 9 or 10, wherein the composition is used as an agent for inhibiting virus proliferation.

12. The sealed body according to claim 9 or 10, wherein a cosmetic raw material composition containing said composition is contained in said container.

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