JP2003113079A - Pyoderma treatment - Google Patents

Abstract

(57) Abstract: cis-6-hexadecenoic acid, cis-9-
An agent for preventing or treating pyoderma comprising an unsaturated fatty acid selected from hexadecenoic acid, eicosapentaenoic acid, γ-linolenic acid and oleic acid or a salt thereof as an active ingredient. [Effect] It is useful as a safe and safe preventive or therapeutic agent for pyoderma, which replaces antibiotics.

Description

Description: TECHNICAL FIELD [0001] The present invention relates to a medicament effective for preventing or treating pyoderma which develops in small animals. [0002] Pyoderma occurs in small animals such as dogs and cats, and causes dermatitis, folliculitis, papules, epidermal small rings, itching, pustules and the like. It is a bacterial skin infection presenting. The pathogenic bacteria of pyoderma are Staphylococcus interme
dius), chronic skin disease, immune disorders, malnutrition,
It is thought that the bacterium develops due to hormonal abnormality or the like, and the bacteria grow. [0003] Pyoderma is classified into superficial pyoderma, superficial pyoderma, and deeper pyoderma according to the depth at which bacteria enter the skin. The affected area can be treated by washing or shaving the affected area with a combined skin cleanser, shampoo, cream, gel, or lotion, but it can be treated by superficial pyoderma or deep follicle damage caused by deep hair follicle damage Treatment of pyoderma requires administration of appropriate antibacterial agents such as antibiotics. Until now, antibiotics such as lincomycin, clindamycin and erythromycin have been used as therapeutic agents for pyoderma (Latest Veterinary Dermatology, 199).
5 years, published by Bunei-do), but systemic and long-term administration may be necessary, and there is a problem in terms of side effects, appearance of resistant bacteria, excessive sterilization of bacteria indigenous to the skin, and more safety. It has been desired to develop a prophylactic / therapeutic agent having a high level of effectiveness. [0005] An object of the present invention is to provide an agent for preventing or treating pyoderma, which is highly safe and does not cause side effects or resistant bacteria even when administered for a long time. [0006] The present inventors have searched for a highly safe antibacterial substance instead of an antibiotic, and found that a specific unsaturated fatty acid or a salt thereof has been added to Staphylococcus intermedius. It showed excellent antibacterial activity and was useful as a prophylactic or therapeutic agent for pyoderma. That is, the present invention provides a pyoderma containing an unsaturated fatty acid selected from cis-6-hexadecenoic acid, cis-9-hexadecenoic acid, eicosapentaenoic acid, γ-linolenic acid and oleic acid or a salt thereof as an active ingredient The present invention provides a prophylactic or therapeutic agent. BEST MODE FOR CARRYING OUT THE INVENTION Among the unsaturated fatty acids of the present invention, cis-6-hexadecenoic acid and cis-9-hexadecenoic acid are main components of sebum constituting a barrier of the outermost layer of human skin. Eicosapentaenoic acid, γ-linolenic acid, and oleic acid are also widely used as foods, and are all harmless even when administered to animals for a long time. Then, as shown in Examples below, these unsaturated fatty acids or salts thereof show excellent antibacterial activity against Staphylococcus intermedius and, when applied to the back of dogs, show the number of bacteria of the bacteria. Has the effect of reducing Therefore, cis-6-hexadecenoic acid, cis-9
-A drug containing hexadecenoic acid, eicosapentaenoic acid, γ-linolenic acid, oleic acid or a salt thereof as an active ingredient can be an extremely safe preventive or therapeutic agent for pyoderma. The unsaturated fatty acid of the present invention can be converted into pharmacologically acceptable salts by a conventional method. Examples of such salts include salts with alkali metals such as sodium salts and potassium salts. Examples thereof include salts with alkaline earth metals such as calcium and magnesium, and ammonium salts, and are preferably sodium salts and potassium salts. [0010] Among the unsaturated fatty acids of the present invention, cis-6-hexadecenoic acid can be obtained by a known metathesis reaction or a method using a microorganism (Japanese Patent Laid-Open No. 1-149882, Japanese Patent Publication No. 4-1 / 1991).
No. 2718), or a method of extracting from vine plants (Tungbergia alata), particularly a method of producing from isopropyl palmitate using a microorganism of the genus Rhodococcus (Japanese Patent Publication No. 4-12).
718), cis-6-hexadecenoic acid can be industrially produced. When extracting from the squid Kazura, after immersing or heating and refluxing the whole plant, the stalk, the flower, the leaves or the seeds of the skull or Kazura,
The mixture can be appropriately filtered, concentrated, freeze-dried, etc., and can be obtained as a concentrated extract or a dry powder. As extraction solvents, methanol, ethanol, propanol, butanol, ether, ethylene glycol, propylene glycol, butylene glycol, petroleum ether, hexane, heptane,
Commonly used organic solvents such as cyclohexane, ethyl acetate, acetone, toluene, dichloroethane, chloroform and the like, water and the like can be mentioned, and one or more of these can be used as a mixture. The extraction process is usually 3
The reaction can be carried out at a temperature of about 100 ° C. for several hours to several weeks by a conventional method, and the extract can be further purified by gel filtration, column chromatography, precision distillation and the like. The unsaturated fatty acids or salts thereof of the present invention can be used as such or mixed with pharmaceutically acceptable carriers such as excipients, auxiliaries, stabilizers, thickeners, coloring agents and flavors. , Solid, semi-solid or liquid preparations by conventional methods, specifically, tablets, pills, powders, granules, fine granules, capsules, liquids,
Oral preparations such as emulsions and suspensions, external preparations such as ointments, immersion liquids, sprays, shampoos and powders, and parenteral preparations such as injections and suppositories can be prepared. The pH of the preparation is preferably pH 4 to 8 from the viewpoint of the effect, and more preferably pH 4 to 6. The method of administering such a preparation to animals such as dogs and cats can be administered orally, intravenously, intramuscularly, subcutaneously or intravenously.
Parenteral administration, such as intradermal administration, external administration, transmucosal administration, and rectal administration, may be mentioned. External administration, particularly ointment or spray administration, is preferable, and administration may be performed by adding to feed or drinking water. In the case of administration by mixing with feed, add the above unsaturated fatty acid or its salt directly or in the above formulation to a compound feed mainly composed of corn flour, flour, soy flour, beef flour, fish meat flour, etc. Administration. The dosage of the agent for preventing or treating pyoderma of the present invention varies depending on the dosage form, the animal species to be treated, the individual body weight and condition, but is usually once a day as an unsaturated fatty acid or a salt thereof. -100 mg / kg, especially 10-50 mg
/ Kg is preferred. The preventive or therapeutic agent for pyoderma according to the present invention can be used in combination with other antibiotics and the like, if necessary. In this case, the amount of use of the other agent can be reduced. Can be. Example 1 Evaluation of sterilization in vitro (in a buffer of pH 6) Intermedius standard bacterium (Staphylococcus intermedi)
us standard strain JCM2422) at 37 ° C. for 2 days on SCDLP (Nippon Pharmaceutical Co., Ltd.) plates to grow colonies. One colony was picked from a colony and mixed well with a 10 mL sterile saline. (Bacterial count about 10 ⁷ cells / mL saline) 10 mL of 50 mM phosphate buffer (pH 6) and 100 ppm of various unsaturated fatty acid solutions (cis-6-hexadecenoic acid (95% pure, manufactured by Kao Corporation)) were placed in test tubes. Cis-
9-hexadecenoic acid (manufactured by Sigma), eicosapentaenoic acid (manufactured by Sigma), γ-linolenic acid (manufactured by Sigma),
Oleic acid (manufactured by Sigma)), and the above bacterial solution was
After adding 0 μl, the mixture was stirred well (the number of bacteria was about 10 ⁵ cells / mL).
Reaction solution). After leaving at room temperature for 0, 3, 6, and 24 hours, the reaction solution was subjected to Spiral System (Gunze Sangyo Co., Ltd.)
Smeared on CDLP plate. The plate was cultured at 37 ° C. for 2 days to grow colonies, and the number of bacteria / mL reaction solution was calculated. The results are shown in FIG. Thus, it was confirmed that the unsaturated fatty acid of the present invention exhibited an excellent bactericidal effect on Staphylococcus intermedius. Example 2 Evaluation of sterilization in vitro (in a model solution) Intermedius standard bacterium (Staphylococcus intermedi)
us standard strain JCM2422) or isolate (Staphylococcus inter
medius Beagle dog isolated from the back skin) at 37 ℃
The cells were cultured on SCDLP (Nihon Pharmaceutical Co., Ltd.) plates for 2 days to grow colonies. One colony was picked from a colony and mixed well with 10 mL of sterilized saline. (About 1 bacteria
0 ⁷ cells / mL saline) 3% 1,3-butanediol in 10mL test tube, 1% surfactant ether sulfates K20 (EO = 4) and 1% cis-6-hexadecenoic acid (purity 95%, manufactured by Kao stock (PH 4.5) was added thereto, and 50 μl of the above bacterial solution was added thereto, followed by stirring well. (About 10 ⁵ bacteria
After leaving at room temperature for 0, 1, 3, and 6 hours, the reaction solution was smeared on an SCDLP plate by a spiral system (Gunze Sangyo Co., Ltd.). The plate was cultured at 37 ° C. for 2 days to grow colonies, and the number of bacteria / mL reaction solution was calculated. FIG. 2 shows the results. From this, it was confirmed that cis-6-hexadecenoic acid exhibited an excellent bactericidal effect on Staphylococcus intermedius. Example 3 Evaluation of sterilization on the back of a Beagle dog The back and center of a Beagle dog were 4 cm × 4 cm with a clipper.
She shaved. A large area including the shaved area was thoroughly washed with a pet shampoo. After drying well with a dryer,
Left for 3 days. 3% 1,3 butanediol, 1% surfactant ether sulfate K20 (EO
= 4) and 1% cis 6-hexadecenoic acid (95% pure,
A solution (pH 4.5) consisting of (Kao Corporation) was sufficiently applied by spraying (sprayed about 15 times) until it dripped. Spray application once a day, 11
Went on for consecutive days. 5cm × 5c soaked with 10 mL of 10% glycerin after 0, 2, 4, 7, 9, 11 days
Using a sterile gauze, the dog's skin was gently rubbed to collect bacteria on the skin. In order to inactivate C16F1 as a bactericide, it was diluted 100-fold with an LP diluent (Nippon Pharmaceutical Co., Ltd.). A 100-fold diluted solution was added to a yolk-added mannitol salt LP plate (mannit salt salt medium manufactured by Nissui Pharmaceutical Co., Ltd.) with a LP diluent and egg yolk as a selective medium for staphylococci using a spiral system (Gunze Sangyo Co., Ltd.). ) Smeared on top. After culturing at 37 ° C. for 5 days, the number of colonies that were positive for the yolk reaction and positive for the VP reaction was calculated to be the number of intermedius bacteria / cm ² . The results are shown in FIG. Than this,
It was confirmed that application of cis-6-hexadecenoic acid reduced Staphylococcus intermedius bacteria. The prophylactic or therapeutic agent for pyoderma according to the present invention has excellent antibacterial activity against Staphylococcus intermedius and is extremely safe, so that it can be administered for a long period of time. It is useful as a prophylactic or therapeutic agent for pyoderma in place of antibiotics.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a view showing the bactericidal effect of various unsaturated fatty acids on Staphylococcus intermedius (pH 6)
In buffer). FIG. 2 shows the bactericidal effect of cis-6-hexadecenoic acid on Staphylococcus intermedius (in a model solution). FIG. 3 is a graph showing changes in the bacterial count of Staphylococcus intermedius on a dog back.

   ────────────────────────────────────────────────── ─── Continuation of front page    (72) Inventor Mikio Takaiwa             2606 Akabane, Kaiga-cho, Haga-gun, Tochigi Prefecture Kao Stock Company             In-house laboratory F-term (reference) 4C206 DA04 DA05 MA01 MA04 ZA89                       ZC61

Claims (1)

Claims: 1. cis-6-hexadecenoic acid, cis-9-
An agent for preventing or treating pyoderma comprising an unsaturated fatty acid selected from hexadecenoic acid, eicosapentaenoic acid, γ-linolenic acid and oleic acid or a salt thereof as an active ingredient.