JPS58146511A - Antimycotic composition - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides acuJeacin A and a compound 1 that enhances the biological activity of acuJeacin;
The present invention relates to an antifungal composition containing a fatty acid selected from the group consisting of -oleic acid, linotve, lylunic acid, lauric acid, palmitooleic acid, arachidonic acid and palmitoelaidic acid. Surprisingly, Candida albicans
B811% Increases the natural activity of acreacin A (7) against fungi such as BC759 and B5158A. These strains are maintained in the Smith Kline & French Laboratories Culture Collection.

Individually, the antifungal compositions of the present invention combine 5 to 3500 weight units of oleic acid with 1 weight lift of acreacin A, provided that the minimum amount of acreacin A is 0.089'
Examples include compositions that are μg.

In particular, when at least 0.4 μg of acreasin A is used, the antifungal composition contains 50 to 3500 units of oleic acid per unit of acreasin AXXt.

Similarly, the antifungal composition of the invention contains 5 to 360 weight units of linoleic acid per weight unit of acreacin A;
The minimum amount of aculeacin A is 0.4 μg. In particular, it contains 40 to 360 weight units of linoleic acid and 1 unit of acreacin A when at least 0.625 μg of acreacin A is used.

Furthermore, the antifungal composition of the present invention contains 5 to 180 weight units of lylunic acid and IM amount units of acreacin A, with a minimum amount of acreacin A of 0.4 μf. When at least 0,625 μV of acreacin A is used, the antifungal composition contains 40 to 180
Combine 1 unit of acreacin A.

Further, in Example 2 of the antifungal composition of the present invention, when at least 1.0 μg of acreasin A is used, 250 to 10 μg of acreasin A is used.
Compositions combining 00 weight units of arachidonic acid tolxi >= 1 unit of acreacin A and 500 to 20004
Examples include set 1+5j, which is a combination of i units of palmitoelaidic acid and 1 weight lift of acreacin A.

Acreacin A is a well-known antifungal antibiotic, published in Journal Ope Antibiotics [Journal Ope Antibiotics].
of Antibiotics, 80 (4)
, PP-297-318 1977].

The antifungal activity of the acreasin A and acreasin A fatty acid compositions was determined by disk diffusion method. Enhancement of antifungal activity was tested using three different methods:

il + single concentration of acreacin Ai - and mono-a degree of known fatty acids.

(2) Mixing various concentrations of acreacin A with a single concentration of each fatty acid.

(3) Various concentrations of fatty acids and a single concentration of acreasin A
A mixture of.

As a control, acreacin A and fatty acid anti-inflammatory activities were tested separately. The fatty acids themselves used in the compositions of the invention did not exhibit antifungal activity at the concentrations tested.

The effects of various fatty acids on the antifungal activity of acreacin A were investigated on yeast nitrogenous base (YNB) agar medium (Dif, USA) supplemented with glucose as a carbon source.

Candida albicans B811t [4] was used for investigation. A composition containing 1 weight unit of acreacin A and 5 weight units of fatty acid or its salt was spotted onto an inoculated plate and incubated at 28-37°C for 1 hour.
After 6-18 hours of incubation, the size of the zone of inhibition was measured. The results are shown in Table 1.

Table 1 shows that the acreacin A and fatty acid compositions shown in Table 1, which increased the size of the inhibition zone by 31 DI or more compared to acreacin A (control), significantly increased the specific activity of acreacin A. It is thought that Fi is a synergistic effect.

In addition, YNB agar (Dif
co) Inoculated plate and sabouarud (8abouarud)
)・Candida albicans Baltm of acreacin A using dextrose agar (Difco) inoculated plates.
Further fatty acids were tested to see if they increased intrinsic activity against. Compositions containing 1 μg of acreacin A and various amounts of fatty acids were spotted onto inoculated plates and the size of the zone of inhibition was measured after incubation at 37°C for 16-18 hours. The results of this test and control data are shown in Table 2.

Table 2 Table 2 (Continued) *: Asymmetry inhibition zone Dormitory: Asymmetry inhibition zone Table 2 (Continued) Table 2 (Continued) Table 2 (Continued) Acleacin in both YNB agar and Sabouraud dextrose agar A (control (no fatty acid)) and the inhibition zone size increased by 8 wm or more, indicating that the compositions of acreasin A and fatty acids shown in Table 2 significantly increased the specific activity of acreasin A. , are thought to have a synergistic effect. In addition to the compositions described above, compositions containing 1 unit of acreacin A and 250 weight units of rhinoelaidic acid and 250 weight units of acreacin AI significantly increase the intrinsic activity of r-phosphorus A.

Using a plate inoculated with Candida albicans B811 on Sabouraud dextrose agar,
The antifungal activity of compositions containing a single amount of sodium oleate and various amounts of acreasin A was determined by measuring the zone of inhibition after ˜18 hours of incubation. The results and control data are shown in Table 3.

Table 3 Candida albicans strains B811, BC759 and B515. Compositions containing a single amount of acreasin A and various amounts of sodium oleate by measuring the zone of inhibition after incubation for 16 to 180 hours at 28 to 37° C. using inoculated plates of the aA strain. The antifungal activity was investigated.

This test was also performed on linoleic and linuric acids. The results are shown in Tables 4a, 4b and 4C.

Table 4a Table 4b Table 4C Inoculated plates of Candida abicans strains BBl1, BC759 and B8153A were prepared using stored frozen cultures 1
m! , tributicase/soybean phyllos (BBL) 50
- inoculate the inoculum on a rotary shaker, 37
After 7 h incubation at °C, this (culture 2
− to 50°C on Sabouraud Textulose Agar (Dif
Sono 15- was inoculated into a 150 m long IJ dish and heated to mW.

The antifungal activity of the compositions of the invention is also demonstrated by topical treatment of Candida albicans infected mice, as exemplified below by the composition of acreacin A and oleic acid.

Clinical isolates of Candida albicans were grown on Sabouraud dextrose agar and precultured by incubation at 35°C in mouse serum.

The back of a female mouse (CF-1, 4 to 6 weeks old) was pierced with hairs.
t2m)L, cleaned with 70% alcohol and rubbed with a wire brush. Next, Candida albicans (lO5~1O6CFu/
fR1) was applied, dried, covered with sterile gauze, and allowed to infect for 2 days. After infection, mice were treated with the acreacin A-oleic acid composition, aclef yyAb, and the acleacin A-oleic acid composition. Torimi 7 (Lot
rimin”.

Clotrimazole-8 chering) at 5
The minimum inhibitory concentration (MIC) of acreacin A for each clinical isolate of Candida albicans treated for 1 day was determined and that amount was used in each experiment. Commercially available Lotrimin cream was used in each experiment. As shown in the results of Section 5 below, the acreacin A-oleic acid composition significantly reduced infection compared to acreacin A itself or the control (comparable to 1-IJmin).

Separately, oleic acid was tested and did not inhibit infection. Bacterial contamination was excluded by microscopic examination.

Table 5 The values in Table 5 indicate the following symptoms.

42 The most severe infection, where the infection site is a culture mainly composed of Candida albicans, causes marked erythema.

3: Shows some degree of recovery, but infection is severe.

2: Not severe infection.

l; Very slight infection.

0: No infection.

In view of the antifungal activity described above, an antifungal effective amount of the composition of the present invention can be used as an active ingredient in a pharmaceutically acceptable vehicle such as a solid, semisolid or liquid carrier to inhibit fungal growth. can be prevented. The compositions of the invention in pharmaceutical form can be applied to the area to be treated in the usual manner, such as by sprinkling, spraying, brushing, smearing, soaking, rinsing, or any other suitable means. The composition of the present invention can also be used in the treatment of fungal growth in arable land in the form of a pesticide.

Claims (1)

[Scope of Claims] 11) An effective amount of anti-TCm acreacin A and an amount sufficient to enhance the biological activity of hyacreacin A, such as oleic acid, linau/L/el&, ryuric acid, lauric acid, palmitoleic acid. An antifungal composition comprising a fatty acid selected from the group consisting of , arachidonic acid and palmitoelaidic acid. (2) The composition according to item (1) above, which is a composition for inhibiting Candida albicans infection. (3) The composition according to item (11) above, wherein the fat O is oleic acid. The composition according to item (3) above, wherein the amount of oleic acid is 0.089 μf. (5) The composition according to item (4), wherein the amount of oleic acid is 10 to 850 units by weight per 1 weight unit of acreasin A. 6) The composition according to item (4) above, wherein the amount of oleic acid is 50 to 3,500 units by weight of acreasin A, and at least 0.4 μf of acreasin A. (7) The fatty acid is linoleic acid. The composition according to item fi1, wherein the amount of linoleic acid is 5 to 360 weight units per acreasin Al unit, provided that acreasin A
The composition according to item (7) above, wherein the minimum amount of is 0.4μ. (9) The amount of linoleic acid is at least 0.625 μg per acreasin A1 weight unit, 40 to 360 weight units.
The composition according to item (8) above, containing acreasin A. (10) The composition according to item (1) above, wherein the fatty acid is lylunic acid. (11) The composition according to the above (10), wherein the amount of lylunic acid is 5 to 180 weight units per one weight unit of acreacin A, provided that the minimum amount of acreacin is 0.4 μf. (12) The amount of lylunic acid is 40 to 180 weight units per acreacin A1 weight unit, and at least acreacin A
The composition of item (11) above, containing 0.625 μg. (13) The composition according to item [11] above, wherein the fatty acid is arachidonic acid. (14) Arachidonic acid mold is acreasin Alff1!
unit weight is 250 to 1000 weight units, and contains at least acreasin A1. Said No. (13) containing Oμg
composition of the term. (15) The fatty acid is palmitoelaidic acid (
Composition of item 1). (16) The amount of palmitoelaidic acid is acreacin A1
per weight unit, mJ number (1
Composition of item 5). (17) An antifungal effective amount of acreacin A and an amount of the group consisting of linoleaidic acid and γ-lino)V acid sufficient to enhance the biological activity of acreacin A are contained in an amount of 250 mg per 1 weight unit of acreacin A. An antifungal composition characterized in that the amount of γ-linoleic acid is 2000% by weight per weight unit of acreacin A.