JP3106644B2 - Antibacterial agent having biguanidyl group and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a biguanidyl group (-N
The present invention relates to a novel compound having HC (= NH) NHC (= NH) NH- ), which is useful as an antibacterial agent, and a method for producing the same. The compound of the present invention is a bactericidal, algicidal, antibacterial, antifungal, deodorant, antiseptic fiber treatment agent, resin modifier,
It is useful as a water repellent, cosmetic raw material, release agent, and paint additive.

[0002]

2. Description of the Related Art A typical example of an organopolysiloxane compound is dimethylpolysiloxane, which is used as a silicone oil as a fiber treatment agent, a resin modifier, a water repellent, a cosmetic material, It is used in a wide range of industrial fields such as molding agents and paint additives.

Further, a compound in which an organic functional group such as an amino group, an epoxy group, a hydroxyl group, a carboxyl group, or a polyoxyalkyl group is introduced into a molecular terminal or a side chain of dimethylpolysiloxane is widely used as an organic modified silicone. Used.

[0004] In some of these applications, dimethylpolysiloxane has much more value by having antibacterial properties in addition to lubrication, polishing, surface protection, and water repellency. In order to achieve such an object, it is conceivable to introduce an antimicrobial substituent into dimethylpolysiloxane. However, there are various environments where antimicrobial properties are required, and there are various requirements regarding the antimicrobial spectrum. Also, for example, in a situation where contact with the human body is expected, it is also an essential condition that the toxicity is sufficiently low.

[0005] As antibacterial compounds, various compounds
It has been known. Biguanide-type compounds that have been known to have a biological activity such as antimalarial activity are one of them.

[0006] For example, bis-biguanide compounds having Biguani Jill groups at both ends of the alkylene chain, a strong bactericidal against a wide range of species, the part because of its antimicrobial properties is widely used as a disinfectant And has been studied for a long time.

However, not always clarified fungicidal action mechanism of this class of compounds, not excellent bactericidal uniformly is expressed by the presence of Biguani Jill groups.
Generally, biguanide-type compounds are known to significantly change their biological activity depending on the type of substituent (J. Ch.
em. Soc. , 729 (1946)) In the above bisbiguanides, it has been reported that the length of the alkylene chain in the intermediate portion and the type of the substituent at the terminal greatly affect the bactericidal activity and the bactericidal spectrum (for example, Brit. J). .P
Pharmacol. 9, 192 (1954)).

[0008]

SUMMARY OF THE INVENTION The present invention relates to various materials or their surfaces.
It is an object of the present invention to provide a low-toxicity polysiloxane compound which can be applied to liposomes and imparts antibacterial properties to them .

[0009]

DISCLOSURE OF THE INVENTION The present inventors have produced a group of novel compounds in which a high molecular weight polysiloxane is bonded to the molecular terminal of a biguanide compound. Some of these have very strong bactericidal properties and have been useful as antibacterial agents. Moreover, these compounds have fungicidal active moiety,
Because it is chemically bonded to polysiloxane, which is a polymer, it is superior in durability and durability compared to conventional kneading of antibacterial agents, etc., and it can reduce adverse effects on the human body and environment. Has advantages.

[0010]

SUMMARY OF THE INVENTION Namely, the present invention relates to compounds of the general formula (I): -XYSiO- (wherein, X is an alkyl group of C1 to C5, Y is a monovalent containing biguanide <br/> Ani Gilles group Antimicrobial comprising an organopolysiloxane compound containing a structural unit represented by the formula:
Provide the agent . In the present invention, Y is -Y ¹ -NHC (=
NH) NHC (= NH) NH -Z (Y 1 is C1~C30
(May include an intervening group selected from an oxy group, an azo group, a thio group, a hydroxymethylene group, an oxycarbonyl group, and a phenylene group), and Z is hydrogen, a C1-C20 alkyl group or a phenyl group. (Which may be substituted with a group selected from a halogen, an alkyl group, a fluoroalkyl group, and an alkoxy group)).

X is an organic group generally used in the organopolysiloxane, and is specifically a C1-C5 linear or branched alkyl group. A methyl group and an ethyl group are particularly preferred. Y is a monovalent group containing an Biguani Gilles group, Biguani Jill group acetic acid, citric acid, organic acid or hydrochloric such gluconate, it may also be a salt of an inorganic acid such as sulfuric acid.

[0012] By selecting the substituent Z which binds to Biguani Jill group, but it is possible to change the germicidal and fungicidal spectrum, in order to obtain good antibacterial activity, as the substituents, hydrogen, C1 to A C20 alkyl or phenyl group (where the phenyl group is a halogen, an alkyl group,
Or a group selected from a fluoroalkyl group and an alkoxy group).

[0013] union of siloxane polymer chains and Biguani Gilles group (Y ¹⁾ is an alkylene group (group of C1-C30, azo, thio, hydroxymethylene group, a group selected from oxycarbonyl group and phenylene group May be included).

The viscosity of the polysiloxane is as follows:
0.1 to 1,000,000 CS (25 ° C) is possible, but preferably 50 to 50,000 CS (25 ° C).

Examples of the polysiloxane compound having Biguani Jill groups of the present invention the following compounds are exemplified (symbol in <> in the formula is consistent with the symbol of the compounds in the Examples below). In the case of compound D,
Are randomly present.

[0016]

Embedded image

The present invention also relates to a method for producing the antibacterial agent of the formula (I).
A method of formula (II): -XY²SiO- (wherein X is a C1-C5 alkyl group;²Ha
Which is a monovalent group containing an anoguanidyl group)
Organopolysiloxane compounds containing structural units
General formula (III):Z ¹ NH₂  (Where Z¹Is hydrogen, a C1-C20 alkyl group or
Phenyl))
A method is provided.

The polysiloxane compound containing a cyanoguanidyl group, which is a raw material of the above method, is, for example, NC-N = C (S
CH ₃ ) NH ₂ or NaN (CN) ₂ .

The reaction of the cyanoguanidyl compound of the formula (II) with the amines of the formula (III) is carried out by reacting alcohols such as ethanol, isopropanol and 2-ethoxyethanol, ethers such as ethyl ether and isopropyl ether, benzene and toluene. Aromatic hydrocarbons can be used.

The reaction temperature is 0 to 200 ° C., preferably 60
１５０150 ° C. Reaction conditions such as reaction time is determined depending on the reactivity of the individual compounds, 1～200Hr
Preferably it is 5 to 100 hours. Acids such as hydrochloric acid
Addition is very effective in terms of reaction yield and rate
And the use of an acid salt for the amines of formula (III).
Both are possible.

That is, these compounds may be prepared as a salt of an organic or inorganic acid, and the acid can be removed by treating with an alkali or the like. Also,
Conversely, if necessary, it can be converted to the desired acid salt
It is.

The compounds of the present invention having a Biguani Jill groups may be used like a conventional polysiloxane compound. Further, it may be used by dissolving in an appropriate solvent or adding an appropriate additive depending on the use.

The material to be applied is not particularly limited. For example, if it is used as a fiber treatment agent, the properties such as texture, gloss, flexibility, and water repellency inherently provided by the polysiloxane compound in clothing, bedding, carpet, and the like are imparted. In addition, effects such as the ability to impart antibacterial and deodorant properties are expected, and would be extremely valuable in practice.

[0024]

The present invention will be described in more detail with reference to the following Examples, which do not limit the present invention. Compound A shown in Production Examples in Examples 1 to 4
-D are the compounds A-D described in the above description.

[0025]

[Reference Example 1]

<Synthesis of the following compound>

Embedded image

A polysiloxane compound having an amino group in a 100 ml three-necked flask equipped with a stirrer, a thermometer, a reflux condenser and a nitrogen introducing device (Shin-Etsu Chemical Co., Ltd.)
X22-161A: 10.0 g (11.9 mmol) of a functional group equivalent of 840 g / mol and a viscosity of 29 cs (25 ° C.).
l), 0.69 g of NC-N = C (SCH ₃ ) NH ₂
(6.0 mmol) and 40 ml of isopropanol were charged, and the mixture was heated and refluxed for 22 hours under a nitrogen atmosphere. The solvent was distilled off under reduced pressure to obtain 10.4 g of a pale yellow oil. This oil was dissolved in 100 ml of ethyl ether, washed twice with water, and the ether layer was dried over anhydrous sodium sulfate overnight and filtered.
After passing through , ether was distilled off and 7.5 g of pale yellow oil was obtained.
I got

[0028]

[Reference Example 2]

<Synthesis of the following compound>

Embedded image However, each constituent unit in parentheses exists at random.

The polysiloxane compound was converted to Shin-Etsu Chemical Co., Ltd.
KF-864 (functional group equivalent: 3800 g / mo)
4, viscosity 1700 cs (25 ° C.)) 45.2 g (11.
The same operation as in Reference Example 1 was carried out except for changing the amount to 9 mmol ), to obtain 40.1 g of a pale yellow oil.

[0031]

Example 1 Production of Compound <A> A stirrer, a thermometer, a reflux condenser, and a nitrogen introducing device were provided.
The compound of Reference Example 1 was added to the obtained 100 ml three-necked flask.
6.8 g (4.1 mmol), aniline hydrochloride 0.1.5g
(4.1 mmol) and 40 ml of isopropanol
It was charged and heated and refluxed for 18 hours under a nitrogen atmosphere. Solvent
Evaporation under reduced pressure gave 6.9 g of a pale yellow oil. This o
Dissolve ir in 100 ml of ethyl ether and wash with water twice
The ether layer was dried over anhydrous sodium sulfate overnight and filtered.
After that, the ether was distilled off to obtain 5.8 g of a pale yellow oil.
Obtained. 0.5 g of this oil and 100 ml of ethyl ether
Into a 300 ml eggplant flask equipped with a stirrer,
The mixture was stirred while being dissolved. Then use silica gel (Wako Pure Chemical Industries: Wa)
5.0 g of Kogel C-200) and stirred at room temperature for 1 hour.
did. After distilling off the ethyl ether under reduced pressure,
At 100 ° C. for 2 hours to obtain 5.3 g of a white powder.
Was. AAT using silica gel with this oil adsorbed
Evaluation of antibacterial activity according to CC-100 (Test bacteria: Klebs
iellapneumoniae). result
Are shown in Table 1.

[0032]

Example 2 Preparation of Compound <B> p-chloroaniline hydrochloride 0.66 instead of aniline hydrochloride
g (4.1 mmol ), except that 5.6 g of a pale yellow oil was obtained. Using the obtained compound, silica gel was treated in the same manner as in Example 1 to evaluate antibacterial properties. Table 1 shows the results.

[0033]

Example 3 Preparation of Compound <C> Instead of aniline hydrochloride, n-hexylamine hydrochloride 0.56
The same operation as in Example 1 was performed except that g (4.1 mmol ) was used, to obtain 5.3 g of a pale yellow oil. Using the obtained compound, silica gel was treated in the same manner as in Example 1 to evaluate antibacterial properties. Table 1 shows the results.

[0034]

Example 4 Production of Compound <D> 10.0 g (1.3 mmol ) of the compound of Reference Example 2 was placed in a 100 ml three-necked flask equipped with a stirrer, a thermometer, a reflux condenser, and a nitrogen introducing device. 0.22 g (1.3 mmol ) of p-chloroaniline hydrochloride and 40 ml of isopropanol were charged, and the mixture was heated and refluxed under a nitrogen atmosphere for 28 hours. The solvent was distilled off under reduced pressure to obtain 8.9 g of a pale yellow oil. This oil was dissolved in 100 ml of ethyl ether, washed twice with water, and the ether layer was washed with anhydrous sodium sulfate for 1 hour.
After drying at night, ether was distilled off and a pale yellow oil was obtained.
8 g were obtained. Using the obtained compound, silica gel was treated in the same manner as in Example 1 to evaluate antibacterial properties. Table 1 shows the results
Shown in

[0035]

Comparative Example 1 A silica gel was treated in the same manner as in Example 1 using a raw material polysiloxane compound (x22-161A manufactured by Shin-Etsu Chemical Co., Ltd.) to evaluate antibacterial properties. Table 1 shows the results
Shown in

[0036]

Comparative Example 2 Silica gel was treated in the same manner as in Example 1 using a raw material polysiloxane compound (KF-865 manufactured by Shin-Etsu Chemical Co., Ltd.) to evaluate antibacterial properties. Table 1 shows the results.

[0037]

[Table 1]

The above results show that the compounds of the present invention have excellent antibacterial properties.

[0039]

The antibacterial compound of the present invention makes it possible to impart bactericidal and antibacterial properties to various materials in addition to the unique properties of polysiloxane compounds, and is expected to be applied to a wide range of industrial fields. Is done.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-57-18758 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C08G 77/388 C08G 77/26 C08L 83 / 08

Claims (6)

(57) [Claims] 1. A structural unit represented by the general formula (I): —XYSiO— (wherein X is a C1 to C5 alkyl group and Y is a monovalent group including a biguanidyl group). Antibacterial composed of organopolysiloxane compound
Agent . 2. Y is -Y ¹ -NHC (= NH) NHC
(= NH) NH-Z (Y ¹ is a C1-C30 alkylene group (may include an intervening group selected from an oxy group, an azo group, a thio group, a hydroxymethylene group, an oxycarbonyl group, and a phenylene group) , Z is hydrogen, C1-C1
The antibacterial agent according to claim 1, which is a C20 alkyl group or a phenyl group (which may be substituted with a group selected from a halogen, an alkyl group, a fluoroalkyl group and an alkoxy group). 3. The method according to claim 1, wherein Y ¹ is a C ¹ -C 20 alkylene group, and Z is a phenyl group (which may be substituted with a group selected from a halogen, an alkyl group, a fluoroalkyl group and an alkoxy group). Item 7. The antibacterial agent according to Item 2 . 4. The antibacterial agent according to claim 3 , wherein Y ¹ is a propylene group. 5. A claim 1 or antimicrobial <br/> method according to the 4, the general formula ^(II): -XY 2 SiO- (wherein, X is a C1~C5 An alkyl group, and Y ² is a monovalent group containing a cyanoguanidyl group). An organopolysiloxane compound containing a structural unit represented by the following general formula (III): Z ¹ NH ₂ (where Z ¹ is Hydrogen, a C1-C20 alkyl group or a phenyl group). 6. Anti characterized by introducing Biguanijiru group in a molecular end or side chain of organopolysiloxane
A method for producing a fungicide .