JP4980337B2 - Virus inactivating drug and method for producing the same - Google Patents

Description

  The present invention relates generally to virus inactivating agents, and more particularly to improved virus inactivating agents so that at least avian influenza virus can be inactivated. The invention also relates to a method for producing such a virus inactivating drug.

  Conventional masks only physically prevent the passage of particles, for example, by making the eyes of a nonwoven fabric that is a mask base material fine. However, it was not possible to prevent avian influenza virus, cats, dogs, human calicivirus, and norovirus from entering the body through the mouth only by making the nonwoven fabric finer.

  When attention is paid to antibacterial properties, it is known that ultrafine zinc oxide has excellent characteristics. Conventionally, most antibacterial, antifungal and deodorant agents are organic compounds, which may be problematic in terms of bleed out from the resin and the sustainability of the effect, and may come into contact with the human body or food. The case was difficult to use in terms of safety.

  As an inorganic antibacterial agent, a silver antibacterial agent is generally used, but has problems of blackening due to oxidation and elution of silver ions, and is not necessarily universal. On the other hand, since ultrafine zinc oxide is an inorganic compound, it has no problem of bleeding out, is non-coloring, and maintains a stable effect. Further, as is apparent from the fact that it is used in cosmetics, anti-inflammatory agents, etc., it is also a great feature that it is highly safe for the human body.

  However, the ultrafine zinc oxide has a drawback that it is less effective against moths other than black mold and ringworm, and there is a problem that it needs to be used in accordance with the purpose.

  The present invention has been made in order to solve the above-described problems, and it is an object of the present invention to provide an improved virus inactivating agent that can inactivate an avian influenza virus.

The virus inactivating agent according to the present invention comprises 5 zinc organic acids, wherein zinc oxide nanoparticles are dispersed in an organic acid aqueous solution containing 40 to 50% by weight of an organic acid that partially lactates when dissolved in water. , An aqueous solution containing at a concentration of 10,000 ppm to 10,000 ppm.

  When the virus-inactivating agent according to the present invention was worn on the face and impregnated in the mask, at least avian influenza virus could be inactivated. The mask has a three-layer structure of an outer nonwoven fabric layer / intermediate nonwoven fabric layer / inner nonwoven fabric layer, and the intermediate nonwoven fabric layer is preferably impregnated with the virus inactivating agent according to the present invention. By providing the outer nonwoven fabric layer, the zinc oxide and / or organic acid adhering to the intermediate nonwoven fabric layer is prevented from being scattered to the outside, and by providing the inner nonwoven fabric layer, zinc oxide and / or organic adhered to the intermediate nonwoven fabric layer. Acid can prevent entry into the nose and mouth.

  When the mask impregnated with the virus inactivating agent according to the present invention was worn on the face, the virus that entered the nostril and the oral cavity from the outside could be efficiently killed. The reason for this is thought to be because the cells of avian influenza virus are destroyed and inactivated by the antibacterial activity of zinc oxide and organic acids. It is considered that the antibacterial activity is further enhanced by the synergistic effect of the organic acid and zinc oxide.

  The aqueous organic acid solution in which the zinc oxide nanoparticles are dispersed may be tableted or granulated using a medicinal solid agent or powder additive.

  The organic acid is gluconic acid, acetic acid, citric acid, tartaric acid, malic acid, lactic acid or the like. Among them, gluconic acid that is partially lactated when dissolved in water is preferable.

  By adding 1,3 dimethyl-2-imidazolidine, the solubility of organic acid zinc in water can be increased. 1,3 dimethyl-2-imidazolidine is not toxic.

The zinc oxide nanoparticles preferably include zinc oxide nanoparticles having a diameter of 50 nm to 70 nm (one nano is one billionth). It is also advantageous that ultrafine zinc oxide is well dispersed in organic acids. Metal ions are said to have sterilizing power in the order of Hg>Ag>Cu>Zn>Fe> TiO ₂ , and silver antibacterial agents are generally used. However, by making zinc oxide into ultrafine particles, It has come to show antibacterial properties not inferior to. The antibacterial mechanism of ultrafine zinc oxide is thought to be the same as that of silver ions, and is not due to the toxicity and bactericidal properties of metals. It is thought that some oxygen in the air or water is activated to destroy the cell membrane of the virus. . By using nanoparticles, the specific surface area is increased, the contact on the surface of the virus is expanded, and the growth of the virus is suppressed. Metal ion powder has little elution, high inhibitory effect maintenance and safety, and exhibits antibacterial properties equivalent to silver against viruses that are in direct contact. The virus diameter is 75 nm. It has been found that an avian virus can be inactivated by selecting ultrafine zinc oxide having a diameter close to that of the virus and dispersing it in an aqueous organic acid solution.

When impregnating the viral inactivation agent nonwoven mask, the adhesion amount of the zinc oxide nanoparticles are preferably ^{5g / m 2 ~15g / m 2} .

  As the organic acid, an organic acid that is partially lactated when dissolved in water is preferable. In particular, gluconic acid is preferably used. In this case, more preferably, the concentration is adjusted to include about 7500 ppm of zinc gluconate.

When gluconic acid is dissolved in water, as shown in the following [Chemical Formula 1], a part becomes gluconolactone. This is called equilibrium. The ratio of gluconolactone and gluconic acid varies with temperature, concentration, pH, and the like. When acidified, the amount of acid in water increases, so the proportion of gluconolactone increases. When alkaline, gluconic acid becomes a salt and stabilizes, so the proportion of gluconolactone decreases. Equilibration is like connecting two water tanks with a tube. When water is poured into the left water tank, the water flows to the right through the tube to maintain balance.

Regarding the explanation of the synergistic effect caused by the combined use of zinc oxide nanoparticles and gluconic acid, let us consider the case where gluconic acid touches the protein, avian influenza virus. As shown in [Chemical Formula 2], the protein contains an acidic amino acid and a basic amino acid. Amino acid of the acidic, has a such as -COOH, the negative ion ^- become (COO). Basic amino acids have -NH2 and become positive ions (-NH3 ⁺ ). If there are a lot of positive ions in the protein or a lot of negative ions, the protein will dissolve in water, but if the negative and positive ions are the same (referred to as the isoelectric point), they will be neutral and have no charge. It will not dissolve in. If the virus is set to an isoelectric point, the virus will not melt and will die.

  According to the present invention, the zinc oxide nanoparticles react with gluconic acid to become zinc gluconate, which successfully adjusts the isoelectric point, destroys avian influenza virus cells, and inactivates them. it is conceivable that.

  In this case, antibacterial properties can be increased by further adding fumaric acid, malic acid or citric acid.

The above non-woven ^{fabric, 30g / m 2 ~50g / m} 2 of PET (polyethylene terephthalate) preferably comprises a spunbonded fabric.

Further, the nonwoven fabric of ^{30g / m 2 ~50g / m 2} , may be 70% and PET30% of混抄nonwoven rayon.

  In the method according to another aspect of the present invention, an aqueous solution containing 40 to 50% by weight of an organic acid that partially lactonizes when dissolved in water is prepared, and the resulting organic acid zinc has a concentration of 5,000 ppm to 10,000 ppm. The amount is selected so that the zinc oxide nanoparticles having a diameter of 50 nm to 70 nm are stirred and dispersed in the aqueous solution at room temperature. Gluconic acid is preferably used as the organic acid. It is considered that ultrafine zinc oxide is in the form of ultrafine particles, with the aid of an organic acid, uniformly dispersed in water and dissolved.

  The step of dispersing the zinc oxide nanoparticles in the organic acid aqueous solution is preferably performed so as not to raise the temperature.

  When the mask impregnated with the virus inactivating agent according to the present invention was worn on the face, the virus entering from the outside into the nostril and oral cavity could be efficiently killed.

  For the purpose of obtaining a drug improved so as to be able to inactivate avian influenza virus, zinc oxide nanoparticles having a diameter of 50 nm to 70 nm are obtained in an aqueous gluconic acid solution containing 40 to 50% by weight of gluconic acid. It was found by stirring and dispersing at room temperature so that the concentration of zinc gluconate to be 5,000 ppm to 10,000 ppm was not increased. It was observed that when zinc oxide nanoparticles were dispersed in an aqueous gluconic acid solution, heat was generated, and gelation occurred when the temperature was too high. Moreover, when the density | concentration of the zinc gluconate exceeded 60,000 ppm, it was recognized that it gelatinizes purely. Therefore, it should be noted that the temperature during dispersion and the concentration of zinc gluconate are strictly adjusted. Examples will be described below.

In a 50% aqueous solution of gluconic acid, zinc oxide nanoparticles having a diameter of 50 nm to 70 nm are stirred and dispersed at room temperature so as not to raise the temperature, and zinc gluconate (Gluconic Zn) is 30,000 ppm, 10,000 ppm, 7, Six types of drug test products containing 500 ppm, 5,000 ppm, 3,750 ppm, and 2,000 ppm were prepared. Add 0.5 ml of each sample (sterilized distilled water as a control) and 0.5 ml of avian influenza virus (A / whistling swan / Shimane / 499/83 (H5N3) 10 ^7.5 EID ₅₀ /0.1 ml), mix by vortexing, The reaction was allowed to proceed at room temperature (20 ° C.) for 10 minutes. The test product and virus mixture are serially diluted 10-fold with sterile PBS containing antibiotics, and 0.1 ml is inoculated into the chorioallantoic cavity of three 10-day-old chicken eggs. After the embryonated chicken eggs were cultured at 37 ° C. for 2 days, the presence or absence of virus growth in the chorioallantoic cavity was confirmed by the hemagglutination test, and the virus infection titer was calculated by the method of Reed and Munch. The results are shown in Table 1.

  FIG. 1 is a plot of the relationship between the concentration of Gluconic Zn in the test product and the virus infectivity. As is clear from FIG. 1, the virus infection titer was 2.25 and the minimum value at a gluconic acid concentration of 7,5000 ppm. The reason for showing such a minimum value is not clear.

It is the Example which applied this invention. FIG. 2 is a conceptual diagram of a virus inactivation mask to which a virus inactivation drug according to the present invention is applied. FIG. 3 is a cross-sectional view of a mask base material constituting the mask. With reference to these drawings, the mask 1 includes an intermediate nonwoven fabric layer 3 formed by impregnating a nonwoven fabric with an organic acid solution in which zinc oxide is dispersed. On the front side of the intermediate nonwoven fabric layer 3, an outer nonwoven fabric layer 2 that is in contact with outside air is provided. On the back side of the intermediate nonwoven fabric layer 3, an inner nonwoven fabric layer 4 that is in contact with the skin surface of the nose and mouth is provided. Formed by dispersing the zinc oxide in an organic acid aqueous solution, non-woven fabric impregnated with a viral inactivation agent containing 5,000ppm~10,000ppm gluconate ^{zinc, 30g / m 2 ~50g / m} 2 of PET (polyethylene terephthalate ) spunbonded fabric or ^{30g / m 2 ~50g / m 2} , 70% and PET30% of混抄nonwoven rayon. The coating amount of zinc oxide is ^{5g / m 2 ~15g / m 2} .

  When the mask obtained by this example was worn on the face, the virus that entered the nostril and oral cavity from the outside could be efficiently killed. It is also preferable to add a triethanolamine or ethylene glycol to give a moisturizing effect.

  In the above-described embodiment, a three-layer structure mask is illustrated. However, the present invention is not limited to this, and a four-layer structure or a multilayer structure having more than that may be used.

  It is another Example to which this invention is applied. This virus inactivating drug was harmless even when it entered the body. The virus inactivating agent according to the present invention is placed in a humidifier and sprayed into a room to prevent avian influenza.

  It is a further embodiment to which the present invention is applied. A gluconic acid aqueous solution in which zinc oxide nanoparticles are dispersed is tableted or granulated using a medicinal solid agent or powder additive, and produced into a plate or granule as shown in FIG. And then tableted so that it can be taken. Additives for solid agents or powders include disintegrants, coating agents, binders, excipients, lubricants, sweeteners, colorants and the like. Thereby, avian influenza can be prevented. It may be colored to make it easy to drink, aesthetically, varieties, etc. It may be a tablet that does not dissolve in the stomach but dissolves in the intestine, an oral tablet that gradually dissolves in the mouth, a multi-layer tablet in which two or more drugs act separately, and an injection tablet that is dissolved when used.

  In the above embodiment, gluconic acid is exemplified as the organic acid. However, the present invention is not limited to this, and any one that breaks the protein film in synergy with zinc oxide can be used.

  It should be understood that the embodiments disclosed herein are illustrative and non-restrictive in every respect. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

  The virus inactivating drug according to the present invention inactivates the avian influenza virus.

It is the figure which plotted the relationship between the density | concentration of the zinc gluconate in the test article which concerns on an Example, and a virus infectivity value. It is a conceptual diagram of the virus inactivation mask which applied the virus inactivation chemical | medical agent which concerns on an Example. It is sectional drawing of the virus inactivation mask which applied the virus inactivation chemical | medical agent which concerns on an Example. It is a perspective view of the tablet which made the tablet the gluconic acid aqueous solution formed by disperse | distributing a zinc oxide nanoparticle soaking in an excipient | filler.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Virus inactivation mask 2 Outer nonwoven fabric layer 3 Intermediate nonwoven fabric layer 4 Inner nonwoven fabric layer

Claims (8)

A virus containing zinc oxide nanoparticles at a concentration of 5,000 ppm to 10,000 ppm, in which zinc oxide nanoparticles are dispersed in an organic acid aqueous solution containing 40 to 50% by weight of an organic acid that partially lactates when dissolved in water. Inactivating drug.   The virus-inactivating agent according to claim 1, wherein the zinc oxide nanoparticles include zinc oxide nanoparticles having a diameter of 50 nm to 70 nm. The virus inactivating agent according to claim 1 , wherein the organic acid zinc includes zinc gluconate. The virus inactivating agent according to any one of claims 1 to 3 , wherein 1,3 dimethyl-2-imidazolidine is added. The virus inactivating agent according to any one of claims 1 to 4 , further comprising fumaric acid, malic acid or citric acid.   The virus inactivating drug according to claim 1, wherein the aqueous organic acid solution in which the zinc oxide nanoparticles are dispersed is tableted or granulated using a medicinal solid agent or a powder additive. Prepare an organic acid aqueous solution containing 40-50% by weight of an organic acid that partially lactates when dissolved in water,
The amount of the organic acid zinc obtained is selected so that the concentration is 5,000 ppm to 10,000 ppm, and zinc oxide nanoparticles having a diameter of 50 nm to 70 nm are stirred and dispersed in the organic acid aqueous solution at room temperature. A method for producing a virus inactivating drug. The method for producing a virus inactivating drug according to claim 7 , wherein the step of dispersing the zinc oxide nanoparticles in the organic acid aqueous solution is performed without increasing the temperature.