JPS609728B2 - antifungal agent - Google Patents

Description

[Detailed description of the invention] This invention relates to antifungal agents.

More specifically, this invention relates to general formula (1); CH3(CH
2) Regarding an antifungal agent containing a compound represented by nCH=CHC02R (1) (in the formula, R is a hydrogen atom or a lower alkyl group, and n means an integer of 2 to 10) as an active ingredient. .

Conventionally, various treatments have been attempted for skin mycosis caused by various fungi, including external therapy, internal therapy,
There is physical therapy.

Of these, internal therapy and physical therapy each have their own risks, and external therapy is commonly used for the treatment of skin mycoses as it is convenient*. There are too many antifungal agents to list, but for example, there are known formulations containing undecylenic acid, zinc undecylenate, salicylic acid, thianthol, glycarobin, etc. as active ingredients, in the form of ointments, powders, liquids, etc. .

However, among fungal diseases, the skin disease commonly referred to as athlete's foot is caused by various fungi (eg, white hawk fungus, filamentous fungi, etc.), and conventionally known so-called athlete's foot medicines have some drawbacks. The inventor of this invention conducted intensive research to develop a drug that is effective against various bacteria, and as a result, the Q.8-unsaturated fatty acid represented by the above general formula (1) or its ester was found to be extremely effective. I learned what to show.

Among the active ingredients of this invention, for example, 2-dodecenoic acid is produced as a raw material for perfume preparations and retention agents, and is used as methyl or ethyl ester.It is surprising that antifungal activity was found in such a compound. be.

The above general formula (1) which is an active ingredient of the antifungal agent of this invention
All of these compounds can be produced by known methods.

Among these, Q.8-unsaturated fatty acids (compounds in which R is day in the above general formula) can be produced, for example, as follows. That is, 4 parts of phosphorus trichloride was added to 1.0 mol of the corresponding sufficiently dried saturated acid and 2.2 mol of bromine, and the mixture was heated to 60-70 oo, so that hydrogen bromide was gradually evolved. Control and react for 5-6 hours. After cooling, 1.2 mol of potassium hydroxide or sodium hydroxide is added to form Q-hydroxycarboxylic acid, which is then dehydrated. Also, the target Q
・Knoevenagelcon using malonic acid and a saturated aldehyde that has two fewer carbon atoms than 8-unsaturated fatty acids
It can also be obtained by densation. Further, the ester form can be obtained by a conventional method using the above-mentioned Q/B-unsaturated fatty acid as a raw material.

In the compound of general formula (1) of this invention, the lower alkyl group means an alkyl group having up to 3 carbon atoms, preferably a methyl group. Particularly preferred compounds are those in which R is a hydrogen atom and n is an integer of 8 to 10, and R is a methyl group and n is 6.
~8. The antifungal agent according to the present invention is used as an external preparation, but its dosage form is not particularly limited;
It may be either an ointment or a powder. Preferred dosage forms are solutions (eg spirits) or ointments. For formulation, the compound of general formula (1) above is dissolved in an appropriate base,
The ingredients are dispersed or mixed, and if necessary, penetrating agents, keratin softeners, disinfectants, and emulsifiers, suspending agents, etc. are added to adjust the drug form to enhance or assist the medicinal efficacy, and the preparation is finished. The preparation method can be carried out by conventional methods known in the art. As the alcoholic agent, a solution prepared by dissolving 1 to 5 parts by weight of the compound of general formula (1) and 1 to 5 parts by weight of methyl salicylate in 100 parts by weight of ethyl alcohol is preferred. As the cartilage base, fats, fatty oils, lanolin, glycerin, wax resins, hardeners, higher alcohols, glycols, or mixtures thereof are used.

Preferred ointment bases for this invention include purified lanolin and white petrolatum. In the case of an ointment as well, the concentration of the compound of general formula (1) is preferably 1 to 5% by weight. The preparation thus obtained exhibits excellent medicinal efficacy against skin mycoses.

How to use: Apply to affected area 2 to 3 times per day.

Next, the present invention will be explained with reference to Examples and clinical trials.

Example 1 (Antibacterial activity test) The compounds in Table 1 (in 2500, the compounds No. 1 to 10 are liquid, and the compounds No. 11 and 12 are solid) were each tested at 9/100 [, 9/of 50'
, 500 mtano', 250 mt/similar, 125 mt', 62.5 methanol/desktop concentration,
This was used as the test solution for the antibacterial activity test.

All mediums are Sabouraud agar medium (1 medium contains 10 ml of beptone, 40 ml of glucose, 159 ml of agar. pH 5.8
±0.1) was used. The test bacteria are the 6 shown in Table 1.
different types of bacteria were used. Trichophyton Rubrum IF0
5467 (Trjchophytonmbr dish mIF
05467), Trichophyton mentaglophytes (
Trichoph's Grophtes) and Saburoudedes Kyannis IF0 7863
(Sakaurauditescanis IF0786
Regarding 3), two platinum loops of the bacteria cultured on a slant medium for 7 days were placed in a milk bee containing 4 parts of sterile distilled water, and then transported to sea, and the supernatant liquid was used as cocoon liquid. Candida albicans IF○0583
sIFO0583), Candida lipolytica IFO0
746 (Candi ship 1ipol〆jca m0 07
46) and Satucharomyces cerevisiae ATC
C9763 (Saccharomyces cer
evlslae ATCC9763), take 1 platinum loopful of bacteria cultured on a slant medium for 2 days and add 4 ml of sterile distilled water.
The cells were placed in a test tube containing M and shaken to obtain a bacterial solution. Assay procedure Add 0.1 of each test solution to sterilized Sabouraud agar medium 9.9, simmer, and place in a sterile petri dish.

One platinum loopful of each bacterial solution was inoculated into this, and Trichophyton.
Rufulum IF05467, Trichophyton mesotaglophytes, Subroudytes cyannis '0786
3 for 5 days, also Candida albicans IFO
0583, Rikindida lipolytica m○074n Satucharomyces. For S. cerevisiae ATCC 9763, the presence or absence of growth of each bacterium was visually observed after culturing at 270 ℃ for 4 hours. Table 1 shows the growth inhibition results for each bacterial species. In addition, in Table 1, the symbols mean the following.

−: Growth of bacteria was completely inhibited.

Growth of thirteen bacteria was observed.

Soil: An intermediate state between growth and growth inhibition was observed for bacteria.

Table 1 Table 1 (continued) Example 2 (Minimum inhibitory concentration) In Example 1, sample No. 10, 11, and 12 were found to have strong antibacterial activity against Trichophyton mentagrophytes.
(Minimum inhibitory concentration, Buddha's evening/wind) was determined.

The results are shown in Table 2.

Table 2 Specimen No. 2 considered to be relatively effective in clinical antibacterial activity tests.
A preparation with the following formulation was prepared for No. 10.

Dodecenoic acid (sample No. 10) 2.5 methyl tasalicylate 2.5 taethyl alcohol 50 {The above formulation was applied to the following patient twice a day for 7 days to the extent that the skin was evenly moistened. Case 1 Sweat Foamy White Hawk Male 2Z years old i) The affected area was moist.

ii) The dampness and odor of the affected area disappeared from the day of application.

lll) The depression stopped from the second day. M: Epithelial detachment of the skin decreased from the 3rd day.

Case 2 Sweat Foamy White Hawk Male 2Z≠ i) The affected area was dry.

ii) The shallowness has stopped since the day of application.

Kawa) Skin epithelial detachment decreased from the 3rd day.

Case 3: Allergy-prone male, 30 years old) No changes such as irritation, discoloration, sores, or rash were observed after application.

Claims (1)

[Claims] 1 General formula (I): CH_3(CH_2)nCH=CHCO_2R(I)(
In the formula, R is a hydrogen atom or a lower alkyl group, and n is 2
An antifungal agent comprising a compound represented by the formula (meaning an integer of 10 to 10) as an active ingredient. 2 R in general formula (I) is a hydrogen atom, and n is 8 to 1
The antifungal agent according to claim 1, which is an integer of 0. 3 R in general formula (I) is a methyl group, and n is 6 to 8
The antifungal agent according to claim 1, which is an integer of .