WO1997030057A1

WO1997030057A1 - Antibacterial amino acids, inorganic salts thereof, and process for the preparation and use thereof

Info

Publication number: WO1997030057A1
Application number: PCT/JP1997/000445
Authority: WO
Inventors: Seiichi Yamashita; Takuma Inami
Original assignee: Sangi Co., Ltd.
Priority date: 1996-02-19
Filing date: 1997-02-19
Publication date: 1997-08-21

Abstract

N-(long-chain acyl) basic amino acids and inorganic salts thereof, both exhibiting antibacterial and surface activities, comprising coordination compounds of N-(long-chain acyl) basic amino acids with antibacterial metal ions or compounds, and prepared by mixing an aqueous strongly alkaline solution of an N-(long-chain acyl) basic amino acid with an antibacterial metal compound. These compounds are useful as antibacterial surfactants.

Description

Harm

Antimicrobial amino acid and inorganic salt thereof, production method thereof and use thereof

Technical field

The present invention relates to an antibacterial amino acid and an inorganic salt thereof useful as a surfactant, a method for producing the same, and a use as a surfactant.

Background art

Conventionally, inorganic salts of N-long chain basic amino acids have been used widely as detergents, emulsifiers or dispersants because of their surface activity. The N-long-chain-basic-basic-amino acid used as a raw material for the amino acid salt is, for example, an alkali in a mixed solvent of water and a hydrophilic organic solution.

N-long-chain acyl basic amino acids synthesized by reacting basic amino acids with long-chain fatty acid halides in the presence of 10 amino acids are separated from this synthesis reaction solution without using a crystallization step. No. 57-747092). According to the same method, after preparing a reaction solution for synthesizing an N-acyl basic amino acid to be a mixed solvent of water and a hydrophilic organic solvent, the pH is adjusted from 40 ° C to the boiling point of the hydrophilic organic solvent.

When it is adjusted to In "!-6, it is separated into an aqueous layer and an organic layer containing the amino acid, and the N-long-chain-basyl basic amino acid obtained by removing the solvent from the obtained organic layer can be used as it is. It has a high purity and can separate N-long-chain-basic-amino acids from the N-long-chain-basic-amino-acid synthesizing reaction solution. It can also be applied to the purification of N-acyl basic amino acids.

20 In this way, a process for obtaining N-long-chain basic amino acids with high purity has been established, and inorganic salts of the amino acids are used in a wide range of applications such as detergents, emulsifiers and dispersants, but have no antibacterial activity For this reason, there is a problem in that application to cosmetics, medicines, fibers, resins, and the like, which are required to maintain a high level of hygiene, is restricted.

Disclosure of the invention

Therefore, an object of the present invention is to provide an N-long-chain acetyl basic amino acid having antibacterial activity and a method for producing the same.

As a result of intensive studies, the inventors of the present application focused on the property that the amino group and the carboxyl group of the N-acyl basic amino acid easily coordinate a metal. Excellent N-acyl basic amino acid is obtained The inventors have found that the present invention has been completed.

That is, the present invention provides an antibacterial amino acid or an inorganic salt thereof, in which a compound of an antibacterial metal ion and / or an antibacterial metal is coordinated with an N-long-chain acetyl basic amino acid. The present invention also provides the antibacterial N-long-chain basic amino acid of the present invention, which comprises mixing and neutralizing a strongly alkaline aqueous solution of an N-long-chain basic amino acid with an antibacterial metal or a compound thereof. A method for producing an amino acid or an inorganic salt thereof is provided. Further, the present invention provides a surfactant having an antibacterial activity, comprising the antibacterial N-long-chain acetyl basic amino acid of the present invention or an inorganic salt thereof. Further, the present invention provides a surfactant having an antibacterial activity, produced by the method of the present invention. Since the antibacterial N-acyl basic amino acid of the present invention has both surface activity and excellent antibacterial activity, it can be used in cosmetics, chemicals, fibers, resins, etc., which require antibacterial properties, as detergents, emulsifiers, and dispersants. It can be applied as an agent or the like.

BRIEF DESCRIPTION OF THE FIGURES

1, _c illustrating a powder X-ray diffraction pattern of N- stearoyl lysine was used as a silver-containing N- stearoyl lysine and its manufacturing raw material obtained in the examples below

BEST MODE FOR CARRYING OUT THE INVENTION

The antimicrobial N- long-chain N- long chain Ashiru group Ashiru basic Amino acids of the present invention, but are not limited _{_{to, C n H 2n + 1 C0-}} ( n is an integer of 1 2-2 2) Those represented by are preferred. The alkyl group in the acyl group may be linear or branched, but is preferably linear. Specific examples of preferred long-chain acryl groups include myristoyl groups, palmitoyl groups, stearoyl groups, oleoyl groups, and the like. The term “basic amino acid” to which a long-chain acryl group binds means an amino acid that shows basicity in an aqueous solution, and preferred specific examples include lysine and arginine.

The basic amino acid usually has a plurality of nitrogen atoms, but the long-chain acetyl group may be bonded to any of the nitrogen atoms. May be bonded to the nitrogen atom. However, it is preferable that one long-chain acryl group is bonded to the α-amino group. Examples of preferred Ν-long chain basic amino acids include 亍 -sparoylysine and Ν-myristoyl Examples include, but are not limited to, lysine, N-sparyoylarginine, N-myristoylarginine, N-palmitoyllysine, N-palmitoylarginine and the like.

The N-long chain sacyl basic amino acid may also be in the form of an inorganic salt. In this case, preferred examples of the metal constituting the inorganic salt include alkali metal such as sodium and potassium.

In the antibacterial N-long-chain basic basic amino acid or the inorganic salt thereof of the present invention, an antibacterial metal ion or compound is coordinated to the N-basic basic amino acid or the inorganic salt thereof. Preferred examples of the antibacterial metal include, but are not limited to, silver, copper, and zinc, which are highly safe for the human body.

It is preferable that the ion or compound of the antibacterial metal coordinate with the nitrogen atom in the basic amino acid. Basic amino acids usually have a plurality of nitrogen atoms, but an antibacterial metal ion or compound may be coordinated to any of the nitrogen atoms, or may be coordinated to a plurality of nitrogen atoms. . Further, a compound of an antibacterial metal such as chloride may be coordinated.

The N-long chain acetyl basic amino acid or the inorganic salt thereof of the present invention can be produced by mixing a strong alkali aqueous solution or a strong acid aqueous solution of an N-long chain acryl basic amino acid with an antibacterial metal or a compound thereof. Can be. Mixing can be performed at room temperature.

Preferred examples of the strong alkali used in this method include sodium hydroxide and potassium hydroxide, but are not limited thereto. Preferred examples of the strong acid include hydrochloric acid, but are not limited thereto. The concentration of the alkali in the strong alkali aqueous solution is not particularly limited, but is preferably about 1 to 20% by weight. The concentration of the strong acid in the strong acid aqueous solution is preferably about 1 to 20% by weight. The concentration of the N-long-chain acetyl basic amino acid in the strong aqueous solution or the strong acid aqueous solution is usually about 1 to 20% by weight, preferably 3 to 10% by weight.

The antibacterial metal can be added as a simple metal when it is dissolved in a strong acid or strong alkaline solution to be used to generate metal ions, but it is preferable to use an ionic compound, particularly a water-soluble salt. . As a preferred specific example of such a water-soluble salt, Silver nitrate, silver sulfate, silver acetate, silver lactate, silver perchlorate, silver thiosulfate, etc., which produce copper ions, copper nitrate, copper sulfate, copper acetate, copper formate, copper perchlorate Examples of those that generate zinc ions include zinc nitrate, zinc sulfate, zinc acetate, zinc perchlorate, and the like. For other metals, the same water-soluble metal salts can be used.

The addition amount of the antibacterial metal or its compound is preferably about 0.01 to 3.0% by weight, more preferably 0.5 to 1.0% by weight, based on the N-long chain basic amino acid. About 0% is preferable.

The antibacterial N-long-chain-basic-amino acid formed by the above method is present as a precipitate in the strong acid or strong aqueous solution. The precipitate is washed with distilled water or the like, filtered and taken out, and then dried, or the solution is neutralized and then filtered and dried, whereby a powdery antibacterial amino acid can be recovered. For neutralization, hydrochloric acid is preferably used in the case of basicity, and sodium hydroxide or sodium hydroxide is preferably used in the case of acidity.

Since the antibacterial N-long-chain-basic-basic amino acid and the inorganic salt thereof of the present invention have surface activity and antibacterial activity, they can be used for cosmetics, detergents, chemicals, fibers, resins, etc., which require antibacterial properties. It can be used as an activator. Antibacterial N-long chain basic amino acids and their inorganic salts can be applied by dissolving or kneading the powder or high-concentration solution into the composition, or kneading with fibers or resins. Alternatively, it can be applied by being included in a coating agent composition.

Hereinafter, the present invention will be described more specifically based on examples. However, the following examples are described for illustrative purposes only, and should not be construed as limiting in any way.

Example 1

At room temperature, 1-Og of N-myristoyl lysine was dissolved in 1-OmI of a 5% aqueous sodium hydroxide solution, and then 0.001 g of silver nitrate was added, followed by sufficient stirring.

Example 2

At room temperature, 10 g of N-stearoyl lysine was dissolved in 10 OmI of a 20% aqueous solution of potassium hydroxide, 0.16 g of silver nitrate was added, and hydrochloric acid was added little by little. H was adjusted to 7, and the mixture was stirred well.

Example 3

After dissolving at room temperature, 1 0 percent aqueous solution of sodium hydroxide 1 0 Om I N-stearoyl arginine 3 g, was stirred well by adding silver nitrate 0. 1 5 _g.

Example 4

At room temperature, 5 g of N-myristoylarginine was dissolved in 100 ml of a 1% aqueous sodium hydroxide solution, and 0.2 g of silver lactate was added, followed by thorough stirring.

Example 5

At room temperature, 5 g of N-palmitoyl lysine was dissolved in 10 OmI of a 15% aqueous potassium hydroxide solution, and 0.17 g of silver lactate was added thereto, followed by thorough stirring.

Example 6

Room temperature, after dissolving the N- stearoyl lysine 1 O g of 5% aqueous Natoriumu aqueous 1 00m l, <stirred by the addition of chloroplatinic 0. 46 _g.

Example 7

At room temperature, 8 g of N-sparoylysine was dissolved in 100 ml of a 10% aqueous sodium hydroxide solution, and 0.5 g of chloroauric acid was added, followed by thorough stirring.

Example 8

At room temperature, 2 O g of N-sparoylysine was dissolved in 10 OmI of a 10% aqueous potassium hydroxide solution, and 0.5 g of zinc nitrate was added, followed by thorough stirring.

Example 9

At room temperature, 10 g of N-palmitoylarginine was dissolved in 100 ml of an aqueous solution of 10 <½ hydrogen chloride, and 0.16 g of silver nitrate was added, followed by stirring well.

Example 10 Structural analysis

Surface analysis of the product of each of the above Examples by ESCA (Electron Spectroscopy for Chemical Analysis) confirmed that a metal ion was bonded to the nitrogen atom of the amino group of the N-acyl basic amino acid. In addition, in Examples 2, 6, and 7, it was confirmed that a metal ion was bonded to the nitrogen atom of the amino group, and at the same time, metal chloride was recognized in powder X-ray analysis. It is thought to be coordinated to the nitrogen atom of the amino group. The precipitate obtained in Example 2 was washed, filtered, and dried to obtain an antibacterial N-stearoyl lysine. FIG. 1 shows the result of powder X-ray diffraction of this sample. The upper part of FIG. 1 shows the diffraction pattern of Example 2, and the lower part shows the powder X-ray diffraction pattern of N-stearoyl lysine used in the preparation of Example 2. It can be seen from the diffraction pattern of Example 2 that new intensity peaks appear at angles of 2Θ = 46, 55, and 57 °. On the other hand, the pattern of silver powder X-ray diffraction originally shows an intensity peak at an angle of 20 = 38, 44 °, so the above-mentioned new intensity peak in Example 2 is due to silver alone. It is thought that there is no.

Example 11 1 Antibacterial test

The precipitates obtained in Examples 1 to 9 were washed, filtered, and dried to obtain powder samples. Antimicrobial tests were performed by the shake flask method with the concentration of these samples being 0.1 ppm. For comparison, a similar test was performed using N-sparoylysine, silver chloride and silver nitrate. Silver nitrate was also tested when the sample concentration was set to 0.05 ppm in addition to 0.1 |

In short, this test method involves adding a test sample to a culture solution containing Escherichia coli to the above-mentioned concentration, setting the density of Escherichia coli to 1.6 × 10 ⁵ nom I, shaking culture at 25 ° C, The number of E. coli after 12 hours and after 12 hours is measured. The results are shown in Table 1 below.

table 1

Number of E. coli (pcs m I)

6 hours after start 1 2 hours after Example 1 1.6 X 10 ^s 10 10 Example 2 1.6 x 10 ^s 10 10 Example 3 1.6 x 10 ⁵ 10 10 Example 4 1.6 x 10 ^P 10 ku 10 Example 5 1.6 χ 10 ^a ku 10 ku 10

Five

Example 6 1.6χ10 10 Example 7 1.6 1.610. 10 10 Example 8 1.6χ10. 10 10 Example 9 1.6χ10. C 10 c 10

5 6

N-sparoylysine 1.6 χ 10 ^a 5.8 X 10 3.2 10

Four

Silver chloride 1.6 x 10 ^s 4.0 x 10 5 x 10 ^£ Silver nitrate (sample concentration 0.1 ppm) 1.6 x 10 ³ 10 10

5 3

Silver nitrate (sample concentration 0.05 ppm) 1.6 x 10 2.4 X 10

From the results shown in Table 1, it can be seen that the antibacterial N-long-chain acetyl basic amino acid of the present invention has excellent antibacterial activity.

Claims

The scope of the claims

1. An antibacterial amino acid or an inorganic salt thereof, wherein a compound of an antibacterial metal ion and Z or an antibacterial metal is coordinated to an N-long-chain basic amino acid.

2. Long chain Ashiru group _{_{C n H 2n +, C0- (}} n is 1 2 shows a 2 2 integer) antimicrobial N- long chain Ashiru basic amino acid or an inorganic salt according to claim 1, wherein represented by.

3. The antibacterial N-long-chain acetyl basic amino acid or an inorganic salt thereof according to claim 1 or 2, wherein the basic amino acid is lysine or arginine.

4. The antibacterial N-long-chain basic amino acid or an inorganic salt thereof according to any one of claims 1 to 3, wherein the antibacterial metal is silver, copper or zinc.

5. The antibacterial N-long-chain basyl basic amino acid or an inorganic salt thereof according to any one of claims 1 to 4, wherein the compound of the antibacterial metal is chloride.

6. The antibacterial N-long chain acyl base according to any one of claims 1 to 5, wherein the antibacterial metal ion and / or the compound of the antibacterial metal is coordinated to a nitrogen atom in the basic amino acid. Amino acids or inorganic salts thereof.

7. The antibacterial N-long-chain acetyl basic amino according to claim 1, which comprises mixing a strong aqueous solution or a strong acid aqueous solution of N-long-chain basic amino acid with an antibacterial metal or a compound thereof. A method for producing an acid or an inorganic salt thereof.

8. Long chain Ashiru group _{_{C n H 2n +, C0- (}} n is an integer of 1 2-2 2) The method of claim 7, wherein represented by.

9. The method according to claim 7, wherein the basic amino acid is lysine or arginine.

10. The method according to any one of claims 7 to 9, wherein the antibacterial metal is silver, copper or zinc.

11. The method according to any one of claims 7 to 10, further comprising a step of neutralizing after mixing.

12. The method according to any one of claims 7 to 11, wherein the antibacterial metal compound is a water-soluble salt.

13. A surfactant having an antibacterial activity, comprising the antibacterial N-long-chain acetyl basic amino acid or an inorganic salt thereof according to any one of claims 1 to 6.

14. Antimicrobial manufactured by the method according to any one of claims 7 to 12. Surfactant with power c