JP7609911B2 - Use of N-hydroxyethyl-N-[2-hydroxyalkyl]amine as an antiviral agent, antiviral resin composition, and antiviral article - Google Patents

Description

The present invention relates to an antiviral agent, an antiviral resin composition, and an antiviral article.

Antiviral agents are broadly divided into inorganic antiviral agents and organic antiviral agents, for example. When an inorganic antiviral agent is added to resins, synthetic fibers, paints, etc., the heat resistance and weather resistance of the resulting product is improved. Also, when an organic antiviral agent is added to resins, synthetic fibers, paints, etc., the mechanical strength of the resulting product is improved.

As examples of inorganic antiviral agents, a resin composition containing inorganic particles including metal oxides such as iron oxide and aluminum oxide and cuprous oxide particles (Patent Document 1) and a polycarbonate resin composition containing ions of metals such as silver and zinc (Patent Document 2) have been proposed. As an example of an organic antiviral agent, a resin composition containing an antiviral agent obtained by supporting a sulfonic acid surfactant on an inorganic filler has been proposed (Patent Document 3).

JP 2015-117187 A JP 2021-191831 A JP 2017-218516 A

However, when inorganic antiviral agents are used, there are issues such as a decrease in the transparency of the resulting product and a tendency for physical properties such as mechanical strength to deteriorate. Furthermore, because inorganic antiviral agents contain various metal ions, it is necessary to give careful consideration to the impact on the ecosystem caused by the accumulation of metals.

On the other hand, organic antiviral agents do not necessarily have good heat resistance and weather resistance in themselves, and also have safety issues such as being prone to leaking from the resulting products, such as polymer molded articles. Furthermore, depending on the type, organic antiviral agents can easily reduce the transparency of products such as polymer molded articles and synthetic fibers.

The present invention has been made in consideration of the problems associated with the conventional technology, and has as its object to provide an antiviral agent with excellent safety that can be used to prepare a resin composition capable of producing an antiviral article with excellent transparency, and the use of the same. Another object of the present invention is to provide an antiviral resin composition and an antiviral article using the above-mentioned antiviral agent.

That is, according to the present invention, there are provided the following antiviral agents:
[1] An antiviral agent comprising N-hydroxyethyl-N-[2-hydroxyalkyl]amine represented by the following general formula (1):
RCH(OH) _{CH2NHCH2CH2OH ...} ( ₁ )
(In the above general formula (1), R represents a hydrogen atom or an alkyl group having 1 to 16 carbon atoms.)
[2] The antiviral agent according to the above [1], wherein the N-hydroxyethyl-N-[2-hydroxyalkyl]amine is at least one compound selected from the group consisting of the following (a) to (d):
(a) 2,2'-iminodiethanol (b) 1-[(2-hydroxyethyl)amino]dodecan-2-ol (c) 1-[(2-hydroxyethyl)amino]-tetradecan-2-ol (d) β-[(hydroxyethyl)amino]alcohol (C=11-14, secondary type)

The present invention also provides the following antiviral resin composition.
[3] An antiviral resin composition comprising the antiviral agent according to [1] or [2] above and a resin.
[4] The antiviral resin composition according to [3], wherein the content of the antiviral agent is 0.05 to 10 parts by mass relative to 100 parts by mass of the resin.

Furthermore, according to the present invention, there are provided the following antiviral articles.
[5] An antiviral article formed from the antiviral resin composition according to [3] or [4] above.

The present invention also provides use of the following compounds as antiviral agents:
[6] Use of N-hydroxyethyl-N-[2-hydroxyalkyl]amine represented by the following general formula (1) as an antiviral agent:
RCH(OH) _{CH2NHCH2CH2OH ...} ( ₁ )
(In the above general formula (1), R represents a hydrogen atom or an alkyl group having 1 to 16 carbon atoms.)

According to the present invention, it is possible to provide an antiviral agent with excellent safety that can be used to prepare a resin composition that can be used to manufacture an antiviral article with excellent transparency, and the use of the same. In addition, according to the present invention, it is possible to provide an antiviral resin composition and an antiviral article that use the above-mentioned antiviral agent.

<Antiviral Agents>
Hereinafter, embodiments of the present invention will be described, but the present invention is not limited to the following embodiments. The present inventors found that when N-hydroxyethyl-N-[2-hydroxyalkyl]amine represented by a specific general formula was added to a resin that is a material for various molded articles, fibers, and other products, a resin composition was obtained that could be used to manufacture articles with excellent antiviral properties and transparency even without substantially containing metals, metal ions, and the like, and thus arrived at the present invention. That is, the antiviral agent of the present invention is an organic antiviral agent containing N-hydroxyethyl-N-[2-hydroxyalkyl]amine represented by the following general formula (1), and is preferably substantially composed of only N-hydroxyethyl-N-[2-hydroxyalkyl]amine.
RCH(OH) _{CH2NHCH2CH2OH ...} ( ₁ )
(In the above general formula (1), R represents a hydrogen atom or an alkyl group having 1 to 16 carbon atoms.)

The N-hydroxyethyl-N-[2-hydroxyalkyl]amine is preferably at least one compound selected from the group consisting of the following (a) to (d):
(a) 2,2'-iminodiethanol (b) 1-[(2-hydroxyethyl)amino]dodecan-2-ol (c) 1-[(2-hydroxyethyl)amino]-tetradecan-2-ol (d) β-[(hydroxyethyl)amino]alcohol (C=11-14, secondary type)

(a) 2,2'-iminodiethanol (hereinafter also referred to as "antiviral agent a") is a compound represented by the following formula (a).

(b) 1-[(2-hydroxyethyl)amino]dodecan-2-ol (hereinafter also referred to as "antiviral agent b") is a compound represented by the following formula (b).

(c) 1-[(2-hydroxyethyl)amino]-tetradecan-2-ol (hereinafter also referred to as "antiviral agent c") is a compound represented by the following formula (c).

(d) β-[(hydroxyethyl)amino]alcohol (C=11-14, secondary type) (hereinafter also referred to as "antiviral agent d") is a mixture of a compound represented by formula (b) (antiviral agent b) and a compound represented by formula (c) (antiviral agent c) (CAS registration number 84836-93-1).

In acute toxicity tests, the LD50 of antiviral agent d was 2,130 mg/kg in males and 2,700 mg/kg in females, and it is classified as the safest "not applicable" category in the acute toxicity category for health hazards of the United Nations recommendation GHS (Globally Harmonized System of Classification and Labeling of Chemicals). Furthermore, antiviral agent d is listed in Appendix 1, Table 2, serial number 1229 of the Positive List System for Food Utensils and Containers and Packaging of the Food Sanitation Act promulgated on April 28, 2020, and is approved for use in food utensils and containers and packaging, making it particularly safe. In addition, the softening point of antiviral agent d is 61.5°C, so it has excellent dispersibility in resins. For this reason, by using antiviral agent d, it is possible to manufacture antiviral resin compositions and various articles with higher transparency.

By using N-hydroxyethyl-N-[2-hydroxyalkyl]amine as an antiviral agent, it is possible to obtain antiviral resin compositions and various articles that are superior in various properties such as safety, transparency, and mechanical strength compared to the case where conventional antiviral agents are used.

The antiviral properties of the antiviral agent of the present invention are presumed to be expressed by the following mechanism. First, the secondary amine N-hydroxyethyl-N-[2-hydroxyalkyl]amine forms a quaternary ammonium salt. The quaternary ammonium salt thus formed then induces (i) denaturation of the viral outer shell structure (capsid); (ii) denaturation of proteins on the viral envelope required for infection; or (iii) both denaturation of (i) and denaturation of (ii); thereby expressing the antiviral properties.

<Antiviral resin composition>
The antiviral resin composition of the present invention contains the above-mentioned antiviral agent and resin. The type of resin is not particularly limited. Specific examples of the resin include polyethylene resin, polypropylene resin, polyester resin, polystyrene resin, polyvinyl chloride resin, urethane resin, acrylic resin, polyamide resin, polyvinyl alcohol resin, cellulose resin, phenol resin, and epoxy resin.

The content of the antiviral agent (N-hydroxyethyl-N-[2-hydroxyalkyl]amine) in the antiviral resin composition is preferably 0.05 to 10 parts by mass, and more preferably 0.3 to 5 parts by mass, per 100 parts by mass of resin. If the content of the antiviral agent is less than 0.3 parts by mass per 100 parts by mass of resin, the antiviral properties of the resin composition may be difficult to observe. On the other hand, if the content of the antiviral agent is more than 5 parts by mass per 100 parts by mass of resin, the physical properties of the resin composition may be affected.

The antiviral resin composition may further contain pigments, various additives, other antiviral agents, etc., as necessary, to the extent that the effects of the present invention are not impaired.

<Anti-viral products>
The antiviral article of the present invention is formed from the antiviral resin composition. The type of article is not particularly limited as long as it is formed from the antiviral resin composition. Specific examples of the article include those shown below. Note that the articles shown below may contain various colorants and additives.

(1) Antiviral molded article An antiviral molded article is an article molded from an antiviral resin composition by injection molding, extrusion molding, blow molding, etc. Specific examples of molded articles include food containers, trash cans, stationery, housings for electrical appliances, cosmetic containers, vehicle interior parts, kitchen utensils, bath products, clothing storage products, etc.

(2) Antiviral fiber The antiviral fiber is an article in which an antiviral resin composition is fibrous by spinning or the like. The antiviral fiber is also made into a woven or nonwoven fabric. Further specific examples of such articles include clothing and carpets.

(3) Antiviral Paint The antiviral resin composition can be used as a binder and dissolved or dispersed in various solvents to prepare an antiviral paint.

The present invention will be described in detail below based on examples, but the present invention is not limited to these examples. Note that "parts" and "%" in the examples and comparative examples are based on mass unless otherwise specified.

<Preparing antiviral drugs>
The following antiviral agents a to d were prepared.
Antiviral agent a: 2,2'-iminodiethanol (CAS registration number 111-42-2, Chemical Substances Control Law Official Gazette Reference Numbers 2-302, 2-354)
Antiviral agent b: 1-[(2-hydroxyethyl)amino]dodecan-2-ol (CAS registration number 2615-84-1, Chemical Substances Control Law Official Gazette Reference Number 2-354)
Antiviral agent c: 1-[(2-hydroxyethyl)amino]-tetradecan-2-ol (CAS registration number 56975-13-4, Chemical Substances Control Law Official Gazette Reference Number 2-354)
Antiviral agent d: β-[(hydroxyethyl)amino]alcohol (C=11-14, secondary type) (CAS registration number 84836-93-1, Food Sanitation Act, Positive List System for Food Utensils, Containers and Packaging, Appendix 1, Table 2, serial number 1229)

<Use and evaluation of antiviral agents>
Example 1
Antiviral tests of antiviral agents a to d (technical substances) were carried out using bacteriophage Qβ (non-enveloped virus) and bacteriophage Φ6 (enveloped virus), which are viruses that have bacteria as hosts.

Bacteriophage Qβ was cultured together with a host (Escherichia coli) to prepare a bacteriophage stock solution. The prepared stock solution was diluted with normal bouillon medium (1/500 concentration) to obtain a test solution with an infectivity of 6.7×10 ⁶ to 2.6×10 ⁷ pfu/mL (pfu: plaque forming unit). 10 mL of the obtained test solution was placed in a sterilization test cup, and antiviral agent a was added to the mixture to a concentration of 500 ppm. After slowly stirring for 24 hours at 25°C using a shaker, the mixture was appropriately diluted with peptone-added physiological saline. 0.1 mL of Escherichia coli (host) separately cultured in calcium-added LB medium was added to 2.0 mL of calcium-added LB soft agar medium (kept at about 50°C) and thoroughly stirred. 1.0 mL of the diluted test solution was further added and thoroughly stirred to obtain a mixed solution containing the virus and Escherichia coli. The resulting mixture was layered on a calcium-added LB agar plate medium, and after the medium solidified, it was cultured at 37°C for 16 to 24 hours. The number of plaques of 30 to 300 pfu that appeared on the medium was counted, and the virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated. The virus inhibition rate was calculated from the following formula (the number of digits of the reduced number of plaques (pfu) was used as the number of significant digits).
Inhibition rate (%)
= {(pfu of Comparative Example 1 - pfu of Example) / pfu of Comparative Example 1)} × 100

The virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as above, except that bacteriophage Φ6 was used instead of bacteriophage Qβ, Pseudomonas syringae of the genus Pseudomonas was used as the host, and NB medium was used instead of calcium-added LB medium, and the culture was performed at 25°C. The results are shown in Table 1.

(Examples 2 to 4)
Except for using antiviral agents b to d instead of antiviral agent a, the antiviral properties of the antiviral agents were evaluated in the same manner as in Example 1 above. The results are shown in Table 1.

(Comparative Example 1)
The same test as in Example 1 was carried out except that no antiviral agent was used. The results are shown in Table 1.

<Production and Evaluation of Antiviral Resin Composition and Antiviral Article (1)>
Example 5
100 parts of low-density polyethylene resin and 1.0 part of antiviral agent b were heated and kneaded, and then molded to obtain a transparent sample plate (5 cm x 5 cm). 0.2 mL of the test solution of bacteriophage Qβ prepared in the same manner as in Example 1 was dropped onto the surface of the sample plate. A sterile polyethylene film (4 cm x 4 cm) was placed over the dropped test solution, and the film was pressed lightly to ensure that the test solution was spread over the entire film (film adhesion method). After being kept in an environment of 25°C and a relative humidity of 90% or more for 24 hours, the test solution was washed out with SCDLP medium. The washed-out test solution was appropriately diluted with peptone-added saline, and the virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as in Example 1 described above. The results are shown in Table 2.

The virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as above, except that bacteriophage Φ6 was used instead of bacteriophage Qβ, Pseudomonas syringae of the genus Pseudomonas was used as the host, and NB medium was used instead of calcium-added LB medium, and the culture was performed at 25°C. The results are shown in Table 2.

(Examples 6 and 7)
The antiviral properties were evaluated in the same manner as in Example 5, except that antiviral agents c and d were used instead of antiviral agent b. The results are shown in Table 2.

(Comparative Example 2)
A test similar to that in Example 5 was carried out, except that no antiviral agent was used. The results are shown in Table 2.

<Production and Evaluation of Antiviral Resin Composition and Antiviral Article (2)>
(Example 8)
100 parts of polypropylene resin and 2.0 parts of antiviral agent b were heated and kneaded, and then molded to obtain a transparent sample plate (5 cm x 5 cm). 0.2 mL of the test solution of bacteriophage Qβ prepared in the same manner as in Example 1 was dropped onto the surface of the sample plate. A sterile polyethylene film (4 cm x 4 cm) was placed over the dropped test solution, and the film was pressed lightly to ensure that the test solution was spread over the entire film (film adhesion method). After being kept in an environment of 25°C and a relative humidity of 90% or more for 24 hours, the test solution was washed out with SCDLP medium. The washed-out test solution was appropriately diluted with peptone-added saline, and the virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as in Example 1 described above. The results are shown in Table 3.

The virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as above, except that bacteriophage Φ6 was used instead of bacteriophage Qβ, Pseudomonas syringae of the genus Pseudomonas was used as the host, and NB medium was used instead of calcium-added LB medium, and the culture was performed at 25°C. The results are shown in Table 3.

(Examples 9 and 10)
Except for using antiviral agents c and d instead of antiviral agent b, the antiviral properties and weather resistance were evaluated in the same manner as in Example 8. The results are shown in Table 3.

(Comparative Example 3)
The same test as in Example 8 was carried out, except that no antiviral agent was used. The results are shown in Table 3.

<Production and evaluation of antiviral resin composition and antiviral article (3)>
Example 11
100 parts of saturated polyester and 3.0 parts of antiviral agent b were heated and kneaded, and then spun to obtain a transparent sample fiber. 0.4 g of the sample fiber was placed in a vial, and 0.2 mL of a test solution of bacteriophage Qβ prepared in the same manner as in Example 1 was inoculated. After keeping at 25°C for 4 hours, the test solution was washed out with SCDLP medium. The washed-out test solution was appropriately diluted with peptone-added saline, and the virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as in Example 1 described above. The results are shown in Table 4.

The virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as above, except that bacteriophage Φ6 was used instead of bacteriophage Qβ, Pseudomonas syringae of the genus Pseudomonas was used as the host, and NB medium was used instead of calcium-added LB medium, and the culture was performed at 25°C. The results are shown in Table 4.

(Examples 12 and 13)
The antiviral properties were evaluated in the same manner as in Example 11 above, except that antiviral agents of the types shown in Table 4 were used instead of antiviral agent b. The results are shown in Table 4.

(Comparative Example 4)
A test similar to that in Example 11 above was carried out, except that no antiviral agent was used. The results are shown in Table 4.

<Production and evaluation of antiviral resin composition and antiviral article (4)>
(Example 14)
4.2 parts of antiviral agent a was added to 100.0 parts of a mixed solvent of isopropyl alcohol and water (mass ratio = 1:1), and the mixture was stirred and mixed to obtain a mixed solution. 3.0 parts of the resulting mixed solution was added to 100.0 parts of an acrylic resin binder (trade name "Joncryl HPD-96", manufactured by BASF) prepared to a non-volatile content of 25%, and the mixture was stirred and mixed to obtain a sample. The obtained sample was applied to a PET film subjected to corona treatment using a No. 20 bar coater, and then dried to remove isopropyl alcohol and water, and a transparent coating film was formed in which the amount of antiviral agent a was 0.5 parts relative to 100 parts of non-volatile content of the acrylic resin binder. The formed coating film was cut to a size of 5 cm x 5 cm to prepare a sample plate for antiviral testing. 0.2 mL of a test solution of bacteriophage Qβ prepared in the same manner as in Example 1 was dropped on the surface of the prepared sample plate. A sterile polyethylene film (4 cm x 4 cm) was placed over the dropped test solution, and the film was pressed lightly to ensure that the test solution was spread over the entire film (film adhesion method). After being kept in an environment of 25°C and a relative humidity of 90% or more for 24 hours, the test solution was washed out with SCDLP medium. The washed out test solution was appropriately diluted with peptone-added saline, and the virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as in Example 1 above. The results are shown in Table 5.

The virus infectivity (pfu/mL) and inhibition rate (%) in the test solution were calculated in the same manner as above, except that bacteriophage Φ6 was used instead of bacteriophage Qβ, Pseudomonas syringae of the genus Pseudomonas was used as the host, and NB medium was used instead of calcium-added LB medium, and the culture was performed at 25°C. The results are shown in Table 5.

(Example 15)
The antiviral activity was evaluated in the same manner as in Example 14 above, except that antiviral agent d was used instead of antiviral agent a. The results are shown in Table 5.

(Comparative Example 5)
A test similar to that in Example 14 was carried out, except that no antiviral agent was used. The results are shown in Table 5.

By using the antiviral agent of the present invention, it is possible to produce antiviral resin compositions and various articles that are excellent in safety and transparency.

Claims (2)

Use of N-hydroxyethyl-N-[2-hydroxyalkyl]amine represented by the following general formula (1) as an antiviral agent (excluding use in the treatment of humans):
RCH(OH) _{CH2NHCH2CH2OH ...} ( ₁ )
(In the above general formula (1), R represents a hydrogen atom or an alkyl group having 1 to 16 carbon atoms.) 2. Use of N-hydroxyethyl-N-[2-hydroxyalkyl]amine as an antiviral agent according to claim 1, wherein the N-hydroxyethyl-N-[2-hydroxyalkyl]amine is at least one compound selected from the group consisting of the following (a) to (d):
(a) 2,2'-iminodiethanol (b) 1-[(2-hydroxyethyl)amino]dodecan-2-ol (c) 1-[(2-hydroxyethyl)amino]-tetradecan-2-ol (d) β-[(hydroxyethyl)amino]alcohol (C=11-14, secondary type)