Composition and starting material composition of cosmetic
By adjusting the weight ratio of optical isomers in 2,3-butanediol to minimize (meso)-2,3-butanediol content, the composition achieves effective viral proliferation inhibition and moisturization, addressing the lack of antiviral activity in conventional 2,3-butanediol formulations.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-07-11
- Publication Date
- 2026-04-02
AI Technical Summary
Conventional 2,3-butanediol compositions are not recognized for their antiviral activity due to the presence of (meso)-2,3-butanediol, which promotes viral replication, while (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol suppress viral replication, resulting in negligible overall antiviral effect.
A composition comprising (2R,3R)-2,3-butanediol and/or (2S,3S)-2,3-butanediol, with a weight ratio of (meso)-2,3-butanediol being twice or less than the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, to effectively inhibit viral proliferation.
The composition exhibits significant viral proliferation inhibition, including against both enveloped and non-enveloped viruses, while also providing moisturizing and hygroscopic effects.
Smart Images
Figure JP2024025113_02042026_PF_FP_ABST
Abstract
Description
Composition and raw material composition of cosmetics
[0001] The present invention relates to a composition and a raw material composition of cosmetics.
[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 produced by dehydration. Further, 2,3-BDO has a calorific value of 27,198 kJ / kg comparable to that of methanol (22,081 kJ / kg －１ ) or ethanol (29,055 kJ / kg －１ ) and is a chemical substance having an important potential industrial use as a liquid fuel. Other potential uses include the production of printing inks, perfumes, cosmetic raw materials, fumigants, humidifiers and softeners, explosives and plasticizers, and as a carrier for pharmaceuticals. －１
[0003] In recent years, research has also been conducted on the application of 2,3-BDO as an antibacterial and antiviral agent. Patent Document 1 discloses an antiviral composition comprising 2,3-butanediol and an acid. In this document, 2,3-butanediol itself is disclosed as an alcohol that cannot inactivate viruses. Patent Document 2 discloses an antibacterial agent comprising (meso)-2,3-butanediol, but does not mention its antiviral action. Patent Documents 1, 2 and Non-Patent Document 1 are all incorporated into the present specification.
[0004] Special Table 2018-531991, Special Table 2017-531671
[0005] Customs Central Analysis Report No. 20, 1980, pp. 123-127
[0006] Thus, conventionally, 2,3-BDO has not been recognized as having an antiviral action, and its use as an agent for suppressing virus growth has not been studied at all. An object of the present invention is to provide a composition capable of appropriately exhibiting a virus growth inhibitory effect in the use of 2,3-BDO for which a virus growth inhibitory effect is required.
[0007] The present inventors diligently researched the reasons why 2,3-BDO does not exhibit a virus proliferation inhibitory effect, as mentioned in Patent Document 1, and have newly discovered a correlation between the relative abundance of optical isomers of 2,3-BDO and its virus inhibitory effect.
[0008] Generally, chemically synthesized 2,3-BDO contains three optical isomers: (2R,3R)-2,3-butanediol, (2S,3S)-2,3-butanediol, and (meso)-2,3-butanediol. Figure 2 is a gas chromatography chart showing the relative abundance of optical isomers of 2,3-BDO as described in Non-Patent Literature 1. As shown in Figure 2, typical chemically synthesized 2,3-BDO products contain each optical isomer 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 around 14 min is the peak containing both (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol (indicated by the initial letter r in Figure 2, representing the racemic mixture), and the peak around 16 min is the peak of (meso)-2,3-butanediol (indicated by m in Figure 2)).
[0009] The inventors have discovered that (meso)-2,3-butanediol promotes viral replication, while (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol suppress viral replication. The reason why conventional chemically synthesized 2,3-BDO products are not recognized as having antiviral activity is thought to be that these chemically synthesized 2,3-BDO products contain both (meso)-2,3-butanediol, which promotes viral replication, and (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, which suppress viral replication. As a result of these antagonistic effects, the antiviral activity is observed to be almost nonexistent.
[0010] In this specification, "viral proliferation inhibitory effect" is defined as a situation where administering the target composition results in a lower viral proliferation rate compared to when water is administered.
[0011] The present inventors discovered that viral proliferation can be sufficiently suppressed by adjusting the weight ratio of (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol, and (2S,3S)-2,3-butanediol, and thus conceived the present invention. That is, the composition of the present invention comprises at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and (meso)-2,3-butanediol, characterized in that, in weight ratio, the content of (meso)-2,3-butanediol is twice or less the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol. Furthermore, in terms of weight ratio, the content of (meso)-2,3-butanediol is more preferably 1.5 times or less, even more preferably 0.5 times or less, even more preferably 0.13 times or less, and particularly preferably 0.05 times or less, of the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
[0012] When the optical isomers of 2,3-BDO in the composition are in the above proportions, the virus proliferation inhibitory effect is suitably exhibited.
[0013] The composition of the present invention contains the above-mentioned (2S,3S)-2,3-butanediol, and it is preferable that the content of the above-mentioned (2S,3S)-2,3-butanediol is greater than the content of the above-mentioned (meso)-2,3-butanediol. Furthermore, the composition of the present invention contains the above-mentioned (2R,3R)-2,3-butanediol, and it is preferable that the content of the above-mentioned (2R,3R)-2,3-butanediol is greater than the content of the above-mentioned (meso)-2,3-butanediol. When the optical isomers of 2,3-BDO in the composition are in the above proportions, the virus proliferation inhibitory effect is more favorably exhibited.
[0014] The composition of the present invention contains both (2S,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol, and it is more preferable that the content of (2S,3S)-2,3-butanediol is greater than the content of (2R,3R)-2,3-butanediol and greater than the content of (meso)-2,3-butanediol. When comparing (2S,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol, (2S,3S)-2,3-butanediol shows a higher virus proliferation inhibitory effect. Therefore, when the content of (2S,3S)-2,3-butanediol is within the above range, the virus proliferation inhibitory effect is more favorably exhibited.
[0015] The composition of the present invention contains both (2S,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol, wherein the content of (2R,3R)-2,3-butanediol may be greater than the content of (2S,3S)-2,3-butanediol and greater than the content of (meso)-2,3-butanediol. Comparing (2S,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol, (2R,3R)-2,3-butanediol is colorless and transparent, while (2S,3S)-2,3-butanediol is slightly yellow in color. Therefore, from the viewpoint of the degree of freedom in color adjustment, it is preferable that the composition of the present invention contains more (2R,3R)-2,3-butanediol than (2S,3S)-2,3-butanediol.
[0016] The composition of the present invention does not necessarily have to contain (2S,3S)-2,3-butanediol. As described above, (2R,3R)-2,3-butanediol is colorless and transparent, while (2S,3S)-2,3-butanediol has a slightly yellowish tint. Therefore, from the viewpoint of the degree of freedom in color adjustment, it is preferable that the composition of the present invention does not contain (2S,3S)-2,3-butanediol. It should be noted that even if the composition of the present invention does not contain (2S,3S)-2,3-butanediol, it can still suppress viral proliferation. Furthermore, in this specification, "the composition does not contain (2S,3S)-2,3-butanediol" means that when GC-MS analysis of the composition is performed under the above conditions, there is no peak with an S / N ratio of 3 or higher at the position where (2S,3S)-2,3-butanediol is detected (around 12.8 min in each example and each comparative example). Furthermore, the location where (2S,3S)-2,3-butanediol is detected can be determined using a standard sample.
[0017] The compositions of the present invention preferably do not contain racemic mixtures of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol. This is because the antiviral functions of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol tend to decrease.
[0018] The composition of the present invention is preferably used as a virus proliferation inhibitor. As described above, the composition of the present invention exhibits a virus proliferation inhibitory effect. Therefore, the composition of the present invention is suitable as a virus proliferation inhibitor.
[0019] The cosmetic raw material composition of the present invention is characterized by containing the above-described 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 manufactured from a cosmetic raw material composition containing the composition of the present invention, the cosmetic becomes a cosmetic that exhibits a virus inhibitory effect.
[0020] According to the present invention, it is possible to provide a composition that can appropriately exert a virus proliferation inhibitory effect.
[0021] Figure 1 is a chart showing the results of GC-MS analysis of the composition according to Example 5. Figure 2 is a gas chromatography chart showing the relative abundance of optical isomers of 2,3-BDO as described in Non-Patent Literature 1.
[0022] (Detailed Description of the Invention) The present invention is a composition comprising at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and (meso)-2,3-butanediol, characterized in that, in weight ratio, the content of (meso)-2,3-butanediol is twice or less the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
[0023] (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol exhibit excellent virus proliferation inhibitory effects. Conversely, (meso)-2,3-butanediol promotes virus proliferation. Commercially available 2,3-BDO contains these three optical isomers, so little virus proliferation inhibitory effect is observed. However, in the present invention, the content of (meso)-2,3-butanediol is less than twice the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol by weight, thus exhibiting a virus proliferation inhibitory effect.
[0024] Furthermore, the composition of the present invention exhibits an inhibitory effect on viral replication against enveloped viruses and non-enveloped viruses.
[0025] Furthermore, because the composition of the present invention contains (meso)-2,3-butanediol, it can exhibit high moisturizing and hygroscopic effects, and can simultaneously exhibit both virus proliferation inhibitory effects and moisturizing and hygroscopic effects (see Chemical Abstracts Service, CAS: 5341-95-7).
[0026] If the composition of the present invention does not contain either (2R,3R)-2,3-butanediol or (2S,3S)-2,3-butanediol, then "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.
[0027] Furthermore, when comparing (2S,3S)-2,3-butanediol with (2R,3R)-2,3-butanediol, (2S,3S)-2,3-butanediol exhibits a higher viral replication inhibitory effect. Therefore, from the viewpoint of viral replication inhibitory effect, it is preferable that the composition of the present invention contains a higher amount of (2S,3S)-2,3-butanediol than the amount of (2R,3R)-2,3-butanediol.
[0028] Furthermore, when comparing (2S,3S)-2,3-butanediol with (2R,3R)-2,3-butanediol, (2R,3R)-2,3-butanediol is colorless and transparent, while (2S,3S)-2,3-butanediol is slightly yellowish. Therefore, from the viewpoint of the degree of freedom in color adjustment, it is preferable that the content of (2R,3R)-2,3-butanediol is greater than the content of (2S,3S)-2,3-butanediol in the composition of the present invention.
[0029] In the composition of the present invention, the content of (meso)-2,3-butanediol is preferably 1.5 times or less by weight ratio of the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, more preferably 0.5 times or less, even more preferably 0.13 times or less, and particularly preferably 0.05 times or less. This is because it has a remarkable effect in suppressing viral proliferation.
[0030] Furthermore, the composition of the present invention may contain both (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, and the weight ratio of (2R,3R)-2,3-butanediol content / (2S,3S)-2,3-butanediol content = 1 / 1000 to 1000 / 1. Alternatively, the weight ratio of (2R,3R)-2,3-butanediol content / (2S,3S)-2,3-butanediol content = 1 / 100 to 100 / 1, and even further, the weight ratio of (2R,3R)-2,3-butanediol content / (2S,3S)-2,3-butanediol content = 1 / 10 to 10 / 1. Furthermore, it is preferable that the composition of the present invention containing (meso)-2,3-butanediol does not contain a racemic mixture containing equal amounts of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol. This is because the antiviral functions of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol tend to decrease.
[0031] The composition of the present invention contains (2S,3S)-2,3-butanediol, and it is preferable that the content of (2S,3S)-2,3-butanediol is greater than the content of (meso)-2,3-butanediol. Furthermore, the composition of the present invention contains both (2S,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol, and it is more preferable that the content of (2S,3S)-2,3-butanediol is greater than the content of (2R,3R)-2,3-butanediol and also greater than the content of (meso)-2,3-butanediol. As described above, (2S,3S)-2,3-butanediol shows a higher virus proliferation inhibitory effect than (2R,3R)-2,3-butanediol. Therefore, when the content of (2S,3S)-2,3-butanediol is within the above range, the virus proliferation inhibitory effect is more favorably exhibited.
[0032] Furthermore, the composition of the present invention contains (2R,3R)-2,3-butanediol, and it is preferable that the content of (2R,3R)-2,3-butanediol is greater than the content of (meso)-2,3-butanediol. Moreover, it is more preferable that the composition of the present invention contains both (2S,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol, and that the content of (2R,3R)-2,3-butanediol is greater than the content of (2S,3S)-2,3-butanediol and also greater than the content of (meso)-2,3-butanediol. (2R,3R)-2,3-butanediol is colorless and transparent, while (2S,3S)-2,3-butanediol is slightly yellow in color. Therefore, it is preferable that the amount of (2R,3R)-2,3-butanediol is greater than the amount of (2S,3S)-2,3-butanediol, as this increases the degree of freedom in adjusting the color of the composition. In particular, when the composition of the present invention is used as a cosmetic ingredient, it is advantageous because it ensures a degree of freedom in adjusting the color of the cosmetic. In the composition of the present invention, (2S,3S)-2,3-butanediol may not be included from the viewpoint of the degree of freedom in adjusting the color of the cosmetic. It should be noted that even if the composition of the present invention does not contain (2S,3S)-2,3-butanediol, it can still suppress viral proliferation.
[0033] In the composition of the present invention, the total content of (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and (meso)-2,3-butanediol is preferably 5% to 100% by weight of the total weight of the composition.
[0034] The composition of the present invention can be used without particular limitation as long as it is used as a viral proliferation inhibitor that can exert a viral proliferation inhibitory effect. Specifically, the composition of the present invention can be used in skin topical preparations, cosmetic compositions, pharmaceutical compositions, food additives, etc. Furthermore, the composition of the present invention can be formulated in the form of, for example, makeup cosmetics, lotions, creams, essences, or packs, and more specifically, in the form of softening lotions, astringent lotions, nourishing lotions, eye creams, nourishing creams, massage creams, cleansing creams, cleansing foams, cleansing waters, powders, foundations, makeup bases, essences, or packs, and the formulation is not particularly limited. In addition, in each formulation, other components can be appropriately selected and blended without difficulty by those skilled in the art, depending on the type of other composition or the intended use. Furthermore, the composition of the present invention can preferably be formulated as a detergent composition, and the formulation is not particularly limited, but specifically, it can be formulated in the form of hand sanitizer, hand wash, body wash, cleansing cream, cleansing gel, cleansing foam, cleansing water, soap, wet wipes, etc. The composition of the present invention may also be sprayed onto areas where a virus proliferation inhibitory effect is needed, or used by being contained in wet wipes, etc.
[0035] The cosmetic raw material composition of the present invention is characterized by containing the above-described 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 manufactured from a cosmetic raw material composition containing the composition of the present invention, the cosmetic becomes a cosmetic that exhibits a virus inhibitory effect.
[0036] The composition of the present invention is preferably stored or transported in a sealed container with an inert gas or air with a humidity of 10% or less (including 0%). This is because moisture absorption can be prevented, thereby preventing deterioration of the composition such as oxidation. Examples of inert gases include nitrogen, argon, helium, and carbon dioxide.
[0037] 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 predetermined proportions. Furthermore, optical isomers of 2,3-BDO can also be produced using microorganisms, for example, as described in Japanese Patent Publication No. 10-234390 (Bacillus bacteria), Japanese Patent Publication No. 2015-518736 (genetically modified Escherichia coli), Japanese Patent Publication No. 2004-357639 (genetically modified Escherichia coli), etc. (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol, and (2S,3S)-2,3-butanediol are commercially available, specifically as (meso)-2,3-butanediol (manufactured by Sigma-Aldrich, catalog number 361461), (2R,3R)-2,3-butanediol (manufactured by Tokyo Chemical Industries (TCI), catalog number B1161), and (2S,3S)-2,3-butanediol (manufactured by Tokyo Chemical Industries (TCI), catalog number B1343), respectively. Japanese Patent Publication No. 10-234390, Japanese Patent Publication No. 2015-518736, and Japanese Patent Publication No. 2004-357639 are incorporated into this specification.
[0038] (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 (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol, and (2S,3S)-2,3-butanediol can be quantitatively and qualitatively analyzed by gas chromatography-mass spectroscopy (GC-MS) analysis and chiral column analysis. The separation technology for the three optical isomers of 2,3-BDO is owned by Agilent Technologies, Inc., and for example, the three optical isomers of 2,3-BDO can be separated under the following analytical conditions. Furthermore, quantification is possible by creating a calibration curve using standard samples of each optical isomer.
[0039] Apparatus: GC / MS: Agilent Technologies 7890A / 5975C Measurement Conditions Column: CP-Chirasil, 25 m × 0.25 mm id × 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) Inlet: 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
[0040] The following matters are described in this specification.
[0041] The present disclosure (1) includes at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and (meso)-2,3-butanediol, and in terms of weight ratio, the content of the above (meso)-2,3-butanediol is 2 times or less the total content of the above (2R,3R)-2,3-butanediol and the above (2S,3S)-2,3-butanediol. It is a composition characterized by this.
[0042] The present disclosure (2) is the composition according to the present disclosure (1), in which, in terms of weight ratio, the content of the above (meso)-2,3-butanediol is 1.5 times or less the total content of the above (2R,3R)-2,3-butanediol and the above (2S,3S)-2,3-butanediol.
[0043] The present disclosure (3) is the composition according to the present disclosure (1), in which, in terms of weight ratio, the content of the above (meso)-2,3-butanediol is 0.5 times or less the total content of the above (2R,3R)-2,3-butanediol and the above (2S,3S)-2,3-butanediol.
[0044] The present disclosure (4) is the composition according to the present disclosure (1), wherein, in terms of weight ratio, the content of the (meso)-2,3-butanediol is 0.13 times or less of the total content of the (2R,3R)-2,3-butanediol and the (2S,3S)-2,3-butanediol.
[0045] The present disclosure (5) is the composition according to the present disclosure (1), wherein, in terms of weight ratio, the content of the (meso)-2,3-butanediol is 0.05 times or less of the total content of the (2R,3R)-2,3-butanediol and the (2S,3S)-2,3-butanediol.
[0046] The present disclosure (6) is the composition according to any one of the present disclosures (1) to (5), wherein the composition contains the (2S,3S)-2,3-butanediol and the content of the (2S,3S)-2,3-butanediol is more than the content of the (meso)-2,3-butanediol.
[0047] The present disclosure (7) is the composition according to any one of the present disclosures (1) to (5), wherein the composition contains the (2R,3R)-2,3-butanediol and the content of the (2R,3R)-2,3-butanediol is more than the content of the (meso)-2,3-butanediol.
[0048] The present disclosure (8) is the composition according to any one of the present disclosures (1) to (7), wherein the composition contains both the (2S,3S)-2,3-butanediol and the (2R,3R)-2,3-butanediol, the content of the (2S,3S)-2,3-butanediol is more than the content of the (2R,3R)-2,3-butanediol, and the content of the (2S,3S)-2,3-butanediol is more than the content of the (meso)-2,3-butanediol.
[0049] The present disclosure (9) is the composition according to any one of the present disclosures (1) to (7), wherein the composition contains both the (2S,3S)-2,3-butanediol and the (2R,3R)-2,3-butanediol, the content of the (2R,3R)-2,3-butanediol is more than the content of the (2S,3S)-2,3-butanediol, and the content of the (2R,3R)-2,3-butanediol is more than the content of the (meso)-2,3-butanediol.
[0050] Disclosure (10) is a composition according to any one of Disclosures (1) to (5) and (7) that does not contain (2S,3S)-2,3-butanediol.
[0051] Disclosure (11) is a composition according to any one of Disclosures (1) to (7) wherein the composition does not contain a racemic mixture of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
[0052] Disclosure (12) is a composition according to any one of Disclosures (1) to (11) used as a virus proliferation inhibitor.
[0053] The present disclosure (13) is a cosmetic raw material composition characterized by comprising the composition described in any one of the above disclosures (1) to (12).
[0054] (Examples 1-8) and (Comparative Examples 1-3) Compositions according to Examples 1-8 were prepared by mixing (meso)-2,3-butanediol (Sigma-Aldrich product no. 361461), (2R,3R)-2,3-butanediol (Tokyo Chemical Industry product no. B1161), (2S,3S)-2,3-butanediol (Tokyo Chemical Industry product no. B1343) and water (ion-exchanged water) in the weight ratios shown in Table 1.
[0055] Furthermore, the composition according to Comparative Example 1 is a composition consisting only of water, while Comparative Example 2 is a composition mixed with (meso)-2,3-butanediol and water. In addition, Comparative Example 3 is a composition containing (2R,3R)-2,3-butanediol, (2S,3S)-2,3-butanediol, (meso)-2,3-butanediol and water, in a weight ratio of (2R,3R)-2,3-butanediol:(2S,3S)-2,3-butanediol:(meso)-2,3-butanediol = 1:1:4.25.
[0056] GC-MS analysis was performed on the composition according to Example 5, as described in "(Method for measuring the proportion of optical isomers of 2,3-BDO in the composition)" above. Figure 1 is a chart showing the results of the GC-MS analysis of the composition according to Example 5. As shown in Figure 1, it was demonstrated that even if (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol are present in the composition, they can be separated. Furthermore, it was demonstrated that the weight percentages of the content of (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol can also be calculated based on this chart.
[0057] (Measurement of remaining phage virus count) The viral proliferation inhibitory effect was measured by measuring the remaining phage virus count using the compositions of each example and each comparative example 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 the solution was autoclaved at 120°C for 10 minutes. The solution was placed in a petri dish (90 mmφ × 15 mm), cooled and solidified to prepare a 1.5% LB agar medium. (2) 300 μL of the composition of each example and each comparative example was mixed with bacteriophage Qβ (10 ８(3) Mix 300 μL of (cpu / ml) and stir three times by inverting the mixture, then let it stand at room temperature for 4 hours. (4) Mix 200 μL of the solution from (2) with 9.8 mL of SCDLP solution. SCDLP solution was prepared by dissolving Wako Pure Chemical Industries' product "Nutrient Broth" in water to adjust the concentration to 41.8 g / L, and then autoclaving at 121°C, 2 atm, for 20 minutes. (5) Mix 1 mL of the solution from (3) into a test tube containing E. coli (100 μL). (6) Add 4 mL of 0.5% LB agar solution, prepared by mixing 10 g of tryptophan, 5 g of yeast extract, 10 g of sodium chloride, and 15 g of agar with 1 L of water and maintaining at 45°C, to 1 mL of the solution from (4), and stir once by inverting the mixture. (6) The liquid from (5) above was placed in the LB agar medium petri dish from (1) above, and the liquid from (5) above was spread over the surface of the agar medium by slowly rotating the petri dish. (7) After that, it was left at 37°C for 16 hours. (8) The number of plaques that appeared in the petri dish was counted visually. The results are shown in Table 1.
[0058]
[0059] Next, we will explain the plaques that appear in the petri dish during step (8) above. By performing step (7) above, E. coli proliferates, and a colony of E. coli is formed across the entire surface of the LB agar medium in the petri dish. If active bacteriophages (viruses) remain in the liquid from step (5) above, the bacteriophages (viruses) dissolve the cell membrane of the E. coli, causing the E. coli to disappear. In that area, no E. coli colony is formed, and only the LB agar medium remains. This area of only LB agar medium formed by the disappearance of E. coli is called a plaque, and the number of remaining bacteriophages (viruses) can be counted by counting the number of plaques. A large number of such plaques means that there are many active bacteriophages (viruses), and a small number of plaques means that there are few active bacteriophages (viruses). In this experiment, a small number of plaques indicates that the bacteriophage (virus) activity was suppressed by the compositions of the examples and comparative examples in step (2). In other words, a small number of observed plaques indicates that the compositions used in step (2) have a high bacteriophage (virus) proliferation inhibitory effect.
[0060] (Antiviral activity evaluation using bacteriophages) To evaluate the antiviral activity (hereinafter referred to as "antiviral activity") of the compositions according to Examples 1 to 8 and Comparative Examples 1 to 3, the viral inactivity was measured using a modified method of the antiviral activity test method for visible light-responsive photocatalytic materials, JIS R1756. Specifically, the compositions according to Examples 1 to 8, water (Comparative Example 1), (meso)-2,3-butanediol aqueous solution (Comparative Example 2), and the composition according to Comparative Example 3 were mixed with bacteriophage Qβ in a sample tube, stirred by inversion, and left for 4 hours to inactivate the bacteriophage (virus). Subsequently, the bacteriophage was used to infect E. coli and left overnight to measure the number of bacteriophages (viruses) that retained their infectivity. The measurement results are expressed as the bacteriophage (virus) inactivity, where the concentration of inactivated bacteriophages (viruses) against E. coli is expressed. Here, the concentration of inactivated bacteriophages (viruses) against E. coli (bacteriophage (virus) inactivity) was used as an indicator of bacteriophage (virus) concentration, and the bacteriophage (virus) inactivity level was calculated based on this bacteriophage (virus) inactivity level.
[0061] Bacteriophage (virus) inactivity is the result of calculating the concentration of bacteriophage (virus) that is inactivated against E. coli by measuring the concentration of bacteriophage (virus) that can infect E. coli using a bacteriophage Qβ concentration of 8.3 million cells / mL in an antiviral test using bacteriophages. In other words, bacteriophage (virus) inactivity is the degree to which the concentration of bacteriophage (virus) that cannot infect E. coli is relative to the bacteriophage Qβ concentration, and can be calculated as (bacteriophage Qβ concentration - concentration of bacteriophage (virus) that can infect E. coli) / (bacteriophage Qβ concentration) × 100.
[0062] The bacteriophage (virus) inactivity level is calculated from this bacteriophage (virus) inactivation level. The bacteriophage (virus) inactivity level is a numerical value (expressed as a negative value) that is expressed as a common logarithm log(1-X), where the original amount of bacteriophage (virus) is set to 1 and the relative amount of bacteriophage (virus) inactivated after the inactivation treatment is X. The larger the absolute value, the higher the ability to inactivate bacteriophage (virus). For example, if 99.9% of the original bacteriophage (virus) is inactivated, the bacteriophage (virus) inactivity level is expressed as log(1-0.999) = -3.00. The bacteriophage (virus) inactivity level is defined as the percentage (99.9% in the above case) of the amount of bacteriophages (viruses) inactivated after bacteriophage (virus) inactivation treatment relative to the total amount of bacteriophages (viruses) before inactivation treatment. The bacteriophage (virus) inactivity level was determined from the bacteriophage (virus) inactivation level in the manner described above. The results are shown in Table 1.
[0063] The viral inactivity in this specification was evaluated in accordance with JIS Z 2801 and JIS L 1922. Note that the sign of viral inactivity is the opposite of that of the antiviral activity value described below. According to JIS L 1922, antiviral activity is observed when the antiviral activity value is 2.0 or higher, and sufficient antiviral activity is evaluated when the antiviral activity value is 3.0 or higher (see Japanese Patent Application Publication No. 2018-177747 incorporated in this specification).
[0064] From the results in Table 1, it can be seen that in compositions where the weight ratio of (meso)-2,3-butanediol is 1.5 times or less, and especially 0.5 times or less, the total weight ratio of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, the number of plaques that appear is almost zero, indicating a high inhibitory effect on viral proliferation. Furthermore, the number of plaques in Comparative Example 2, a mixed composition of (meso)-2,3-butanediol and water, was greater than that of water in Comparative Example 1, indicating that (meso)-2,3-butanediol has a viral proliferation effect. Therefore, this test result explains why 2,3-butanediol ((2R,3R)-2,3-butanediol:(2S,3S)-2,3-butanediol:(meso)-2,3-butanediol = 1:1:4.25), which is manufactured industrially and sold as a reagent, does not show any inhibitory effect on viral replication.
[0065] The reason why viral replication is promoted or inhibited depending on the type of optical isomer of 2,3-BDO is predicted to be as follows. First, by comparing Comparative Example 1 and Comparative Example 2, (meso)-2,3-butanediol is a substance useful for viral replication and is predicted to promote the production of some substance that is biosynthesized during viral replication. On the other hand, (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol are predicted to function as antagonists to (meso)-2,3-butanediol and inhibit the production of some substance that is biosynthesized during viral replication. In other words, it is predicted that when (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol are present, some substance that is biosynthesized during viral replication is not produced, the virus cannot replicate, and as a result, the virus can be inactivated.
[0066] This can also be understood from the results of Comparative Example 3. In Comparative Example 3, the content of (meso)-2,3-butanediol was 2.1 times the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol, and it can be seen that the virus proliferation inhibitory effect was lower than that of water in Comparative Example 2, with a plaque count of 55 and a virus inactivation level of -1.15. Furthermore, in the present invention, as can be understood from Examples 7 and 8, it is understood that even without containing (2S,3S)-2,3-butanediol, a virus proliferation inhibitory effect can be obtained if the amount of (meso)-2,3-butanediol is 0.13 times or less by weight ratio of (2R,3R)-2,3-butanediol, and especially 0.05 times or less. Furthermore, when a comparative moisturizing test was conducted on (meso)-2,3-butanediol, (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol in accordance with the moisturizing test of Japanese Patent Application Publication No. 2002-212021 incorporated into the specification of this application, it was found that the moisturizing properties of (meso)-2,3-butanediol were higher than those of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
[0067] Thus, the composition of the present invention has excellent effect in suppressing viral proliferation and can be used in applications where such suppression of viral proliferation is required, such as as a raw material for cosmetics.
Claims
1. A composition comprising at least (2R,3R)-2,3-butanediol and / or (2S,3S)-2,3-butanediol and (meso)-2,3-butanediol, characterized in that, by weight, the content of (meso)-2,3-butanediol is 2 times or less the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
2. The composition according to claim 1, wherein, by weight, the content of (meso)-2,3-butanediol is 1.5 times or less the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
3. The composition according to claim 1, wherein, by weight, the content of (meso)-2,3-butanediol is 0.5 times or less the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
4. The composition according to claim 1, wherein, by weight, the content of (meso)-2,3-butanediol is 0.13 times or less the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
5. The composition according to claim 1, wherein, by weight, the content of (meso)-2,3-butanediol is 0.05 times or less the total content of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
6. The composition according to claim 1, wherein the composition comprises the (2S,3S)-2,3-butanediol, and the content of the (2S,3S)-2,3-butanediol is greater than the content of the (meso)-2,3-butanediol.
7. The composition according to claim 1, wherein the composition comprises the (2R,3R)-2,3-butanediol, and the content of the (2R,3R)-2,3-butanediol is greater than the content of the (meso)-2,3-butanediol.
8. The composition according to claim 1, wherein the composition comprises both (2S,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol, wherein the content of (2S,3S)-2,3-butanediol is greater than the content of (2R,3R)-2,3-butanediol and greater than the content of (meso)-2,3-butanediol.
9. The composition according to claim 1, comprising both (2S,3S)-2,3-butanediol and (2R,3R)-2,3-butanediol, wherein the content of (2R,3R)-2,3-butanediol is greater than the content of (2S,3S)-2,3-butanediol and greater than the content of (meso)-2,3-butanediol.
10. The composition according to any one of claims 1 to 5 and 7, wherein the composition does not contain (2S,3S)-2,3-butanediol.
11. The composition according to any one of claims 1 to 7, wherein the composition does not contain a racemic mixture of (2R,3R)-2,3-butanediol and (2S,3S)-2,3-butanediol.
12. The composition according to any one of claims 1 to 11, used as a virus proliferation inhibitor.
13. A cosmetic raw material composition characterized by comprising the composition described in any one of claims 1 to 12.