JP2014084297A - Agent for enhancing effect of antiseptic or antibiotic - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enhance the effect of an antiseptic or antibiotic, thereby reducing the amount of an antiseptic or antibiotic blended into products such as pharmaceuticals, cosmetics, and food products.SOLUTION: A composition includes isothiocyanate and an antiseptic or antibiotic.

Description

  The present invention relates to a preservative or antibacterial effect enhancer. The present invention also relates to a composition comprising a preservative or antibacterial agent and an isothiocyanate.

  Antiseptics and antibacterial agents are added to various products such as pharmaceuticals, cosmetics and foods for the purpose of preventing corruption. However, it is thought that there are cases where health hazards such as allergies are caused by applying or ingesting drugs, cosmetics, and foods that contain a large amount of preservatives and antibacterial agents, especially in the recent health boom. There is a need to reduce the amount of preservatives and antibacterial agents incorporated in such products as much as possible.

  For example, paraben is a general term for paraoxybenzoates and includes various types such as methyl paraben, propyl paraben, and butyl paraben. Paraben is widely used as a preservative or antibacterial agent in pharmaceuticals, cosmetics, foods and the like. However, parabens are highly irritating to the skin and are thought to cause allergies in some cases. For this reason, parabens are required to be displayed as display designation components. Attempts have been made to reduce the amount of parabens used as much as possible, and cosmetics that do not contain any parabens have been developed.

WO2002 / 015722

  An object of the present invention is to enhance the effect of a preservative or an antibacterial agent, and to reduce the blending amount of the antiseptic or antibacterial agent in products such as pharmaceuticals, cosmetics, and foods.

  The present inventors have surprisingly found that isothiocyanate enhances the effects of preservatives and antibacterial agents, and have made further improvements to complete the present invention.

That is, the present invention includes, for example, the subject matters described in the following sections.
Item 1.
A composition comprising an isothiocyanate and a preservative or antibacterial agent.
Item 2.
Item 2. The composition according to Item 1, wherein the preservative or antibacterial agent is paraben.
Item 3.
The paraben is represented by the following formula (I):

(In the formula, R represents an alkyl group having 1 to 8 carbon atoms or a benzyl group.)
And a compound represented by the following formula (II):

(In the formula, R represents an alkyl group having 1 to 8 carbon atoms or a benzyl group.)
Item 3. The composition according to Item 1 or 2, which is at least one selected from the group consisting of compounds represented by:
Item 4.
Item 4. The composition according to any one of Items 1 to 3, wherein the isothiocyanate is at least one selected from the group consisting of sulforaphane, allyl isothiocyanate, benzyl isothiocyanate, methyl isothiocyanate, and ethyl isothiocyanate.
Item 5.
Item 5. The composition according to any one of Items 1 to 4, which is used for antiseptic or antibacterial purposes.
Item 6.
A preservative or antibacterial effect enhancer comprising isothiocyanate.
Item 7.
Item 7. The preservative or antibacterial effect enhancer according to Item 6, wherein the isothiocyanate is at least one selected from the group consisting of sulforaphane, allyl isothiocyanate, benzyl isothiocyanate, methyl isothiocyanate, and ethyl isothiocyanate.
Item 8.
Item 8. The antiseptic or antibacterial effect enhancer according to Item 6 or 7, which is an enhancer of the antiseptic or antibacterial effect of paraben, comprising isothiocyanate.
Item 9.
The paraben is represented by the following formula (I):

(In the formula, R represents an alkyl group having 1 to 8 carbon atoms or a benzyl group.)
And a compound represented by the following formula (II):

(In the formula, R represents an alkyl group having 1 to 8 carbon atoms or a benzyl group.)
Item 9. The antiseptic or antibacterial effect enhancer according to Item 8, which is at least one selected from the group consisting of compounds represented by:

  According to the present invention, the antiseptic effect or antibacterial effect of the antiseptic or antibacterial agent is enhanced, and thus the preservative effect or antibacterial effect is maintained or enhanced in products such as pharmaceuticals, cosmetics, and foods, and the blending amount of the antiseptic or antibacterial agent Can be reduced.

Growth of budding yeast (Saccharomyces cerevisiae) using YPD medium (1% Yeast Extract, 2% Peptone, 2% Glucose) supplemented with sulforaphane (SFN) and various parabens with a cell turbidity of 1 × 10 ⁶ cells / ml The result of having examined SFN and various paraben density | concentration (minimum growth inhibitory density | concentration) required in order to inhibit this by the liquid culture medium dilution method is shown. Using YPD medium (1% Yeast Extract, 2% Peptone, 2% Glucose) supplemented with SFN and various parabens, budding yeast (Saccharomyces cerevisiae) with a cell turbidity of 1 × 10 ⁶ cells / ml by liquid medium dilution method ) Shows the results of examination of various paraben concentrations (minimum growth inhibitory concentrations) necessary for inhibiting the growth of. Growth of budding yeast (Saccharomyces cerevisiae) with a cell turbidity of 1 × 10 ⁶ cells / ml in YPD medium (1% Yeast Extract, 2% Peptone, 2% Glucose) supplemented with SFN, ethyl paraben, and both The results of studying the growth inhibitory action are also shown. Saccharomyces cerevisiae with a cell turbidity of 1 × 10 ⁶ cells / ml was added to YPD medium (1% Yeast Extract, 2% Peptone, 2% Glucose) to which SFN, ethylparaben, and both were added simultaneously. 3 shows the results of static culture at 30 ° C. and examination of the survival of cells (Colony forming unit: CFU) over time.

  Hereinafter, the present invention will be described in more detail.

  The present invention relates to a composition comprising an isothiocyanate and a preservative or antibacterial agent.

  Examples of the isothiocyanate include sulforaphane, allyl isothiocyanate, benzyl isothiocyanate, methyl isothiocyanate, and ethyl isothiocyanate. Of these, sulforaphane is preferable. An isothiocyanate can be used individually by 1 type or in combination of 2 or more types.

  Examples of the antiseptic or antibacterial agent include known antiseptics or antibacterial agents particularly used in pharmaceuticals, cosmetics, and foods. Specifically, parabens, phenoxyethanol, benzalkonium chloride, benzoates (particularly sodium benzoate) , Potassium benzoate, calcium benzoate). Of these, parabens are preferred.

  When using parabens as an antiseptic or antibacterial agent, known parabens with known antiseptic or antibacterial effects can be preferably used. Among them, the following formula (I):

The compound shown by these is preferable. In formula (I), R represents an alkyl group having 1 to 8 carbon atoms (1, 2, 3, 4, 5, 6, 7, or 8) or a benzyl group. Carbon number of the alkyl group is preferably 1-6, more preferably 1-4. The alkyl group may be linear or branched. Specific examples of the alkyl group are preferably a methyl group, an ethyl group, a propyl group, an n-butyl group, an isopropyl group, and an isobutyl group.

  Moreover, following formula (II):

The compound represented by can also be preferably used as a paraben. R in the formula (II) is the same as described above.

  Particularly preferable parabens include methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isopropyl paraben, isobutyl paraben, benzyl paraben, methyl paraben sodium, ethyl paraben sodium, ethyl paraben sodium, propyl paraben sodium and butyl paraben sodium.

  In addition, antiseptic | preservative or an antibacterial agent can be used individually by 1 type or in combination of 2 or more types.

  The composition containing the isothiocyanate and the preservative or antibacterial agent of the present invention is not particularly limited as long as the effects of the present invention can be obtained, but the isothiocyanate is preferably 0.8 per mol of the preservative or antibacterial agent. 2 mol or more, More preferably, 0.2-1 mol, More preferably, 0.5-1 mol is contained.

  Although it is not limited, the composition according to the present invention is preferable because of its excellent antibacterial activity against fungi or fungi, specifically, antibacterial activity against Candida, Escherichia coli, Aspergillus, yeast and the like.

  The composition containing the isothiocyanate and the preservative or antibacterial agent of the present invention may be a composition comprising the isothiocyanate and the preservative or antibacterial agent, and may further contain other components. The total content of swissothiocyanate and preservative or antibacterial agent in the composition may be, for example, 0.1 to 100% by mass. The composition of the present invention can be preferably used as an antiseptic or antibacterial composition. The composition of the present invention can be preferably used as a pharmaceutical composition, a cosmetic composition, a food additive composition, or a food composition. In this case, the antiseptic or antibacterial agent exhibits antiseptic or antibacterial effects, Isothiocyanate has the effect of enhancing the effect of antiseptics or antibacterial agents.

  When used as a pharmaceutical composition, the active ingredient and, if necessary, other ingredients are further added to the composition. Other ingredients include pharmaceutically acceptable bases, carriers, and / or additives (eg, solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants). Etc.). The form of the composition is not particularly limited, and can be used as, for example, tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules and the like. The pharmaceutical composition of these forms can be prepared by a conventional method by combining the other components and isothiocyanate and an antiseptic or antibacterial agent as necessary.

  When used as a cosmetic composition, the active ingredient and, if necessary, other ingredients are further added to the composition. Other ingredients include bases, carriers, and / or additives that are allowed to be added to cosmetics (eg, solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, Examples thereof include lubricants and the like. Further, the form of the composition is not particularly limited, and for example, lotion, lotion, milky lotion, cream, pack agent, beauty essence, facial cleanser, makeup agent, hair care product, body soap, bath agent, fragrance, deodorant And deodorizing agents. The cosmetic composition of these forms can be prepared by a conventional method by combining the other components and isothiocyanate and an antiseptic or antibacterial agent as necessary.

    When used as a food additive composition, the food additive and, if necessary, other components are further blended in the composition. Examples of other components include bases, carriers, additives that are acceptable in food hygiene, and other components and materials that can be used as food additives. The form of the composition is not particularly limited, and examples thereof include liquid, powder, flake, granule, and paste. More specifically, seasonings (soy sauce, sauce, ketchup, dressing, etc.), flakes (sprinkles), grilled meat sauce, spices, roux paste (carrere paste, etc.) and the like can be exemplified. Such a food additive can be prepared by a conventional method in combination with the other components as well as an isothiocyanate and an antiseptic or antibacterial agent as necessary.

    When used as a food composition, food and other ingredients are further blended into the composition as required. Examples of other components include bases, carriers, additives that are acceptable in food hygiene, and other components and materials that can be used as food. Also, the form of the composition is not particularly limited. For example, processed foods, beverages, health foods (nutrient functional foods, foods for specified health use, etc.), supplements, foods for sick people (hospital foods, sick foods, nursing foods, etc.) Etc. can be illustrated. These can be prepared by a conventional method by combining the other components and isothiocyanate and an antiseptic or antibacterial agent as necessary.

  The present invention also includes preservative or antibacterial effect enhancers, including isothiocyanates. The preferred isothiocyanate contained in the preservative or antibacterial effect enhancer, and the preferred preservative or antibacterial agent for applying the effect enhancer are described above for the composition comprising isothiocyanate and preservative or antibacterial agent. The same as the preferred isothiocyanate, as well as the preferred preservative or antimicrobial agent.

  Further, the antiseptic or antibacterial effect enhancer is not particularly limited as long as the effect of the present invention can be obtained, but isothiocyanate is preferably 0.2 mol or more, more preferably with respect to 1 mol of the antiseptic or antibacterial agent. It is applied so as to be 0.2 to 1 mol, more preferably 0.5 to 1 mol. Moreover, the said antiseptic | preservation or antibacterial effect enhancer may consist of an isothiocyanate, and may contain another component, unless the effect of this invention is prevented. Examples of other components include, but are not limited to, excipients, binders, fragrances, and suspending agents. The antiseptic or antibacterial effect enhancer can be solid or liquid. The content of the antiseptic or antibacterial effect enhancer isothiocyanate is not particularly limited, and may be, for example, about 0.1 to 100% by mass.

  The use mode of the antiseptic or antibacterial effect enhancer is not particularly limited, and includes, for example, (i) used in the manufacture of pharmaceuticals, cosmetics, foods, etc. in combination with the antiseptic or antibacterial agent, and (ii) contains the antiseptic or antibacterial agent. Examples of use include oral medicines, oral cosmetics, orally ingested with foods, (iii) external medicines containing preservatives or antibacterial agents, and use as external preparations with external cosmetics.

  The present invention also provides a method of enhancing the antiseptic or antibacterial effect of the antiseptic or antibacterial agent by combining the isothiocyanate and the antiseptic or antibacterial agent.

  Hereinafter, the present invention will be specifically described, but the present invention is not limited to the following examples. In the following example, sulforaphane is used as an isothiocyanate, and the sulforaphane may be abbreviated as “SFN”.

Example 1
Growth of budding yeast (Saccharomyces cerevisiae) 1 × 10 ⁶ cells / ml was performed by a liquid medium dilution method using a YPD medium supplemented with SFN and various parabens (methyl paraben, ethyl paraben, propyl paraben, isopropyl paraben, or butyl paraben). Various paraben concentrations (minimum growth-inhibiting concentrations) required for inhibition were examined. The YPD medium used was prepared by dissolving 1% Yeast Extract, 2% Peptone, and 2% Glucose in ion-exchanged water and autoclaving. SFN was added to the YPD medium at a concentration of 0 μM, 125 μM, 250 μM, 500 μM, or 1000 μM. The results are shown in FIG. From the results, it was confirmed that the amount of paraben required to inhibit the growth of yeast was reduced by adding SFN.

Example 2
The combination of the bacterial species used and the medium was changed as shown in Table 1, the paraben added to the medium was changed to methyl paraben or ethyl paraben, and the SFN addition concentration was changed, and the fungus used was the same as in Example 1. Various paraben concentrations (minimum growth-inhibiting concentrations) required to inhibit the growth of seed 1 × 10 ⁶ cells / ml were examined. In addition, the composition of the used culture medium is as follows.

YPD medium: 1% Yeast Extract, 2% Peptone, 2% Glucose
Malt medium: 2.5% Malts Extract
Bouillon medium: 3% Nutrient Broth

  The results are shown in FIG. From the results, it was confirmed that the amount of paraben required to inhibit the growth of each bacterial species (Candida, Aspergillus, E. coli) was reduced by adding SFN.

  In addition, among the results of Examples 1 and 2, the examination results (specifically, the minimum growth inhibitory concentration of methylparaben or ethylparaben) obtained by adding SFN to 0 μM or 500 μM medium are collectively shown in Table 2. The unit of numerical values shown in Table 2 is mg / ml.

Example 3
Growth of budding yeast (Saccharomyces cerevisiae) with a cell turbidity of 1 × 10 ⁶ cells / ml in YPD medium (1% Yeast Extract, 2% Peptone, 2% Glucose) supplemented with SFN, ethyl paraben, and both The results of studying the growth inhibitory action are shown in FIG. In FIG. 3, the blackened portion indicates that turbidity is generated due to cell proliferation.

  Ethylparaben alone was confirmed to inhibit cell growth at a concentration of 5 mg / ml, but by adding it simultaneously with 1 mM SFN, the amount of ethylparaben added was reduced to 0.25 mg / ml. Was able to inhibit cell proliferation.

Example 4
Saccharomyces cerevisiae with a cell turbidity of 1 × 10 ⁶ cells / ml was added to YPD medium (1% Yeast Extract, 2% Peptone, 2% Glucose) to which SFN, ethylparaben, and both were added simultaneously. And static culture at 30 ° C. FIG. 4 shows the results obtained by sampling a certain amount from the culture solution over time and determining cell viability (CFU) by the colony counting method.

  Ethylparaben alone showed bactericidal action at a concentration of 5 mg / ml, but in a medium containing 1 mM SFN, it shows bactericidal action by adding 0.15-1.25 mg / ml ethylparaben. Was confirmed.

Claims (9)

A composition comprising an isothiocyanate and a preservative or antibacterial agent. The composition according to claim 1, wherein the preservative or antibacterial agent is paraben. The paraben is represented by the following formula (I):

(In the formula, R represents an alkyl group having 1 to 8 carbon atoms or a benzyl group.)
And a compound represented by the following formula (II):

(In the formula, R represents an alkyl group having 1 to 8 carbon atoms or a benzyl group.)
The composition of Claim 1 or 2 which is at least 1 sort (s) selected from the group which consists of a compound represented by these. The composition according to any one of claims 1 to 3, wherein the isothiocyanate is at least one selected from the group consisting of sulforaphane, allyl isothiocyanate, benzyl isothiocyanate, methyl isothiocyanate and ethyl isothiocyanate. The composition according to any one of claims 1 to 4, which is used for antiseptic or antibacterial purposes. A preservative or antibacterial effect enhancer comprising isothiocyanate. The preservative or antibacterial effect enhancer according to claim 6, wherein the isothiocyanate is at least one selected from the group consisting of sulforaphane, allyl isothiocyanate, benzyl isothiocyanate, methyl isothiocyanate and ethyl isothiocyanate. The antiseptic or antibacterial effect enhancer according to claim 6 or 7, which is an enhancer of the antiseptic or antibacterial effect of parabens, comprising isothiocyanate. The paraben is represented by the following formula (I):

(In the formula, R represents an alkyl group having 1 to 8 carbon atoms or a benzyl group.)
And a compound represented by the following formula (II):

(In the formula, R represents an alkyl group having 1 to 8 carbon atoms or a benzyl group.)
The antiseptic or antibacterial effect enhancer according to claim 8, which is at least one selected from the group consisting of compounds represented by:

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