JPS62230713A - Cariostatic agent - Google Patents

Abstract

PURPOSE:To provide a cariostatic agent containing a methylpiperazine derivative as an active component, exhibiting remarkable growth-inhibition activity against Streptococcus mutans which is a main bacterial strain to cause caries and useful for the prevention and remedy of caries by compounding to an antibacterial agent for dental use, etc. CONSTITUTION:The objective cariostatic agent contains a methylpiperazine derivative of formula (A is -CO- or CH2-; n is 12-18) as an active component. The compound of formula includes 1-dodecanoyl-4-methylpiperazine (n=12), 1-tetradecanoyl-4-methyl-piperazine (n=14), etc., as an acyl derivative wherein A is -CO- group and 1-dodecyl-4-methylpiperazine (n-12), etc., as an alkyl derivative wherein A is -CH2- group. Especially preferable compound is 1-tetradecyl-4- methylpiperazine (n=14). The compound of formula is used as a main component and administered in the form of various drugs containing an antibacterial agent for dental use, etc.

Description

[Detailed description of the invention] [Industrial field of application] The present invention provides an anti-corrosion agent effective for the prevention and treatment of cankerosis.
A.

[Conventional technology]

l1lAf14! It is an endogenous infection caused by microorganisms present in the tooth cavity, and it is well known that many microorganisms are contained in the dental plaque adhering to the enamel surface of the tooth. In addition, among the above microorganisms, mutans φ streptococcus ['A (5treptococcus Ilu
tans) is also known to play a particularly important role in the development of caries.

Therefore, various chemotherapeutic agents have been proposed for the prevention and treatment of the above-mentioned MM disease. For example, fluorine has a health-strengthening effect and a bactericidal effect, and is used in the form of topical preparations, mouth rinses, drinking water additives, and the like. Furthermore, bis-biguanides such as chlorhexidine and alexidine have bactericidal and plaque inhibiting effects, and are used as topical preparations and mouth rinses. Furthermore, benzethonium chloride and other quaternary ammonium salt compounds, phenol and other carbolic acid compounds have bactericidal activity, and are mainly used in mouthwashes. Furthermore, it has been reported that certain antibiotics have the effect of inhibiting the formation of dental plaque and acne when they are absorbed into the body or administered as topical agents.

[Problem that the invention seeks to solve]

However, conventional anti-adhesive agents such as those listed in section 1-1 have problems such as not being expected to have definitive antibacterial or therapeutic effects.
The emergence of an essentially effective anti-algae combination agent has been long awaited.

The object of the present invention is to develop a novel piperazine derivative anti-fAfM drug, which has a completely different molecular structure from conventional anti-fAfM agents. The object of the present invention is to - solve the problems of the prior art described above.

[Technical means to solve problems]

Therefore, the anti-algae combination agent according to the present invention.

General formula (wherein A is -C〇- group or -CH2- group, n is 12-
It is characterized by containing a methylpiperazine derivative represented by (which is an integer of 18).

The methylpiperazine derivatives mentioned above include 1-dodecanoyl-4-methyl-piperazine (n=12), 1-tetradecanoyl-
4-Methyl-piperazine (n=14), 1-hexadecanoyl-4-methyl-piperazine (n=16), 1-octadecalyl-4-methyl-piperazine (n=18)
1-dodecyl-4-methyl-piperazine (n=
12), 1-tetradecyl-4-methyl-piperazine (
n=14), 1-hexadecyl-4-methyl-piperazine (n=16), 1-octadecyl-4-methyl-piperazine (n=18)? is included.

The above-mentioned acyl derivative of methylviperazine can be synthesized, for example, by reacting N-methyl-piperazine and acid chloride, and the alkyl derivative of methylviperazine can be synthesized, for example, by reacting N-methyl-piperazine with acid chloride, and the alkyl derivative of methylviperazine can be synthesized by, for example, hydrogenating a bipedal acyl derivative. It can be synthesized by reacting aluminum lithium and aluminum chloride using a known method.

[Action of the invention]

The methylpiperazine derivative represented by the above general formula (1) is 611%! l! It exhibits a remarkable growth-promoting IF effect on the above-mentioned Streptococcus mutans, which is said to be the main causative bacterium, and is therefore suitable as the main component of an anti-&A combination.

] In order to demonstrate the effect of inhibiting two-legged starting, in the methylpiperazine derivative represented by the general formula (i), A is -C〇-
A group with n of 8.10.12.14.16.18 and 20, and A with -CH2- group with n of 8.10.12.14
．． 16. The severity of the above bacterial species against serotype C bacteria for 18 and 20 g) I +l-f+1! ! m
(Table 1 shows the results measured by PJ T l” '19tft 1L4=. In addition, in the above measurement,
All methylpiperazine derivatives are in the form of hydrochloride in order to be water-soluble.

(2-fold dilution method) BHI broth medium (37 g/I) overnight (18-18
Time) The cultivated bacterial solution of Streptococcus mutans (serotype C bacteria) is diluted with a new liquid medium and used as a bacterial solution for inoculation.

” - What is the extract dilution series of methylpiperazine derivatives? 0
0.50.25.12.5.6.25.3.125,
1.5B, 0.784 g/ml, and methanol was used as a control.

A fixed amount of inoculating bacterial solution was inoculated into each diluted extract solution using a pipette, and cultured at 37°C for 8 hours. In that case, the reaction system is B
HI bouillon culture 11! ! 4.8ml, extract dilution 0.
The growth of the bacteria was determined by the presence or absence of macroscopic turbidity, and the minimum growth concentration (MI
C) was obtained.

<Table 1> (1st place: g/l) Table 1 above
Therefore, in the methylbiperazine derivative represented by the general formula (1), n is 8.10.12.14.16.18 and 2.
Among those with n of 0, those with n of 12 to 18 are 12.5 lg/
It can be seen that it can be used on the upper back as a component of an anti-algae mixture since it can obtain a low MIC of less than ml.

Among them, those in which A is a -CO- group and n is 14 to 18 are preferable because they give a low MIC of 8.25 p, g/ml or less, and 1-hexadecanoyl-4 in which n is 16 is particularly preferable.
-Methyl-piperazine is most preferred as it gives a very low MIC of less than 0.78 pg/ml;
is -CH2- group and n is 14 to 18 is '-561L
It is preferable because it can achieve a low MIC of less than g/al by 7F.
In particular, 1-tetradecyl-4-methyl-piperazine where n is 14 is most preferred since it can provide an extremely low MIC of 0.78 gg/ml or less.

Anti-Ml according to the present invention! ! I! The agent contains a methylpiperazine derivative represented by the general formula (I) with extremely low toxicity as a main component, so it can be used, for example, as a dental antibacterial agent or as a topical antibacterial agent.
Medicines, mouth rinses, mouth rinses, or +d caries prevention or It1
It can be provided in a variety of conventionally known active dosage forms, including therapeutic dentifrices and the like.

〔Example〕

The present invention will be specifically explained below using examples.
The present invention is not limited to these examples. Note that in the examples, the middle "part" of each component in the formulation r5 is based on weight.

Example 1 The ingredients of the following composition were kneaded homogeneously by a conventional method.

An anti-erosive oral ointment was prepared. When preparing it,
First, 1-hexadecanoyl-4-methyl-piperazine was ground and kneaded with liquid paraffin, white petrolatum and plastibase were added and kneaded, and sodium carboxymethyl cellulose was further added and kneaded.

<Composition> l-hexadecayl-4-methyl-piperazine

3 parts Sodium carboxymethyl cellulose 31 parts Liquid paraffin 31 parts White petrolatum 12 parts Plastibase 23 parts (Plastibase is a consistency retaining agent made by adding 5% polyethylene with a molecular weight of +21,000 to liquid paraffin and heating it to gel. Example 2 An anti-algae mouthwash was prepared by homogeneously mixing the components shown below.

<Composition> l-tetradecyl-4-methyl-piperazine hydrochloride 932
5th section Hatsuka water 25th section Ice making
500 parts Example 3 The components of the composition described above were mixed homogeneously in the same manner as in Example 2 to prepare an anti-61 corrosion detergent.

Group L^d〉 ■Dodecanoyl 4-methyl-piperazine hydrochloride 411
0 parts Hard water 27 Department ice making 500 parts Example 4 The ingredients of the following composition were homogeneously kneaded by a conventional method to prepare a corrosion-resistant toothpaste.

Composition> l-tetradecyl-4-methyl-piperazine 1 part Sodium monofluorophosphate 0.8 parts Aluminum hydroxide 40 parts Carboxymethyl cellulose sorbitol 19 parts Propylene glycol 2 parts Sodium lauryl sulfate 1 part Sodium saccharin tm fragrance
1 Club activity water production
32.9 parts Example 5 The components having the following composition were homogeneously kneaded by a conventional method.

An anti-algesic powder was prepared.

<Composition> 1-hexadecanoyl-4-methyl-piperazine hydrochloride 1 part calcium carbonate 80 parts glycerin
8 parts Sodium lauryl sulfate
0.5 part saccharin sodium
0.1 part fragrance
1 Club Seisui 3.4
Example 6 The components having the composition shown below were homogeneously kneaded in the same manner as in Example 5 to prepare an anti-algesic powder dentifrice.

(Composition> l-cutadecyl-4-methyl-piperazine salt m112
2 B Calcium carbonate 73 parts Glycerin 8 parts Sodium lauryl sulfate 0.5 parts Sodium saccharin 0.1 part Flavoring
1 Club activity water production
Part 9.4 [Effects of the Invention] As described above, the present invention provides rI! It is possible to provide a novel anti-tIA combination that exhibits a remarkable growth-inhibiting effect on Streptococcus mutans, which is the main bacterium responsible for 4 caries.

that's all

Claims (1)

[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (In the formula, A is -CO- group or -CH_2- group, n is 12
An anti-caries agent characterized by containing a methylpiperazine derivative represented by: 2. The anti-caries agent according to claim 1, wherein the methylpiperazine derivative represented by the general formula (I) is 1-hexadecanoyl-4-methyl-piperazine. 2. The methylpiperazine derivative represented by the general formula (I) is 1-tetradecyl-4-methyl-piperazine.
The anti-caries agent according to claim 1.