JP3124106B2 - Composite powder antibacterial agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composite powder antibacterial agent in which a core substance comprising an inorganic substance or an organic substance is coated with a composition comprising an antibacterial agent, a water-soluble polymer and a dissolving agent.

[0002]

2. Description of the Related Art Conventional antibacterial agents are widely used as preparations such as ointments, creams or liquids (prior art documents: JP-A-54-119023, JP-A-5-19023).
9-70613, JP-A-1-275527, etc.). However, even though these preparations can be easily applied to a diseased site, it is difficult to absorb exudate from an injured site during the healing process and to desiccate the affected site. Therefore, an antibacterial agent is sprinkled with excipients such as talc and zinc white to absorb exudate (trade name: Hybetic U,
Benher Z, Textile, Kozak, etc.) are already commercially available.

[0003]

The exudation and liquid absorption preparations of the conventional preparations absorb exudate from the damaged site, but do not have a sufficient absorption effect. In addition, it is difficult to say that the antibacterial agent has sufficient release and absorption properties from the base and that it is not satisfactory in terms of uniform adhesion to the skin, so that sufficient drug efficacy cannot be expected. . Therefore, the present inventors aim to develop an antibacterial preparation having a sufficient absorption effect, good release from the base and percutaneous absorption, and excellent uniform adhesion to the skin. It is.

[0004]

That is, according to the present invention, there is provided a method for producing a powder having a particle size of 0.1.
0.1 to 5% by weight of an antibacterial agent and 0.2 to 15% by weight of a water-soluble polymer in a core substance of an inorganic substance or an organic substance of 5 to 10 μm
And a composition containing 0.1 to 10% by weight of a dissolving agent.
The present invention also provides the composite powder antibacterial agent, wherein the core substance is selected from silica beads, polyethylene beads, nylon beads, silicon beads, poly (methyl methacrylate) beads, and polystyrene beads. About. Furthermore, the present invention provides an antibacterial agent comprising one or two of croconazole hydrochloride, clotrimazole, isoconazole nitrate, econazole nitrate, sulconazole nitrate, thioconazole, tolnaftate, bifonazole, miconazole, omoconazole, and itraconazole.
The composite powder antibacterial agent is characterized by being selected from at least one kind. As the antibacterial agent, for example, one or two of croconazole hydrochloride, clotrimazole, isoconazole nitrate, econazole nitrate, sulconazole nitrate, thioconazole, tolnaftate, bifonazole, miconazole, omoconazole, itraconazole
More than species can be selected. The compounding amount may be an amount capable of exerting a pharmacological effect, and is usually 0.1 to 5% by weight, preferably 0.5 to 5% by weight.
It may be 2% by weight.

[0005] The inorganic or organic substance serving as the core substance is
It is necessary to be a means for holding the antibacterial agent as the main agent until it is applied to the skin, and an agent for absorbing and holding the exudate so as not to affect the interaction with the main agent, adsorption, and the like. Further, it is preferably spherical because of uniform skin adhesion, fluidity, and a form that can be granulated as a core substance. The combination of these is selected from, for example, silica beads, polyethylene beads, nylon beads, silicon beads, poly (methyl methacrylate) beads, and polystyrene beads. 0.1 to 10 as sphere diameter
It is about 0 μm, preferably 0.5 to 10 μm. If the sphere diameter is too small, coating cannot be performed efficiently, and problems such as aggregation and scattering occur. If it is too large, adhesion to the skin and reduction of drug absorption occur.

The water-soluble polymer may be any water-soluble polymer such as methylcellulose, ethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium alginate, polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, and poly (vinylpyrrolidone). It can be appropriately selected from acrylic acid, sodium polyacrylate, carboxyvinyl polymer, chitosan, hyaluronic acid and the like. These water-soluble polymers serve as a binder between the antibacterial agent as the main agent and the core substance, and also as a binder with the skin. This initially absorbs the exudate from the diseased part, and serves as a carrier to the core substance, thereby promoting the release of the contained antibacterial agent.

[0007] The compounding amount of the water-soluble polymer is 0.2
-15% by weight, preferably 1-10% by weight. If the content is less than 0.2% by weight, desired effects cannot be obtained in terms of binding of the antibacterial agent to the core substance and absorption of leachate.
If it is 5% by weight or more, a fluid composite powder cannot be obtained.

The dissolving agent is not limited as long as it dissolves the contained antibacterial agent. For example, polyhydric alcohols such as ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, propylene glycol, glycerin, isopropyl myristate, and palmitic acid Fatty acid esters such as propyl and hexyl laurate, polyoxyethylene glycol alkyl ethers,
It can be appropriately selected from nonionic surfactants such as polyhydric alcohol acyl ester and polyoxyethylene glycol acyl ester, essential oil components such as peppermint oil, limonene and menthol, crotamiton and the like.

[0009] The solubilizer is 0.1% to 10%, preferably 0.5% to 5%. If the content is less than 0.1%, a desired effect cannot be obtained in dissolution and release of the active ingredient, and 10%
Above, a composite powder cannot be formed.

Next, the production method may be any known granulation apparatus, for example, a pan coating, a fluidized bed granulator, a coat miser, a granulator, a super mixer, a spray drier and the like are appropriately used. Can be More specifically, for example, using a fluidized bed granulator, the core substance is fluidized in the apparatus, and a mixture of an antibacterial agent, a dissolving agent, and a water-soluble polymer previously dissolved in a mixed solvent of ethanol and water is added thereto. The composite powder antibacterial agent of the present invention can be obtained by spraying and coating granulation. When the composite powder antibacterial agent of the present invention is used in a therapeutic setting, it is needless to say that a suitable container such as a pump type container, an aerosol, a metered dose nebulizer and the like can be used.

[0011]

The composite powder antibacterial agent obtained according to the present invention has a uniform and good adhesion to the skin and an improved ability to absorb exudates.
In addition, it exhibits release from the base, remarkable transdermal absorption, and sufficient pharmacological action.

[0012]

The present invention will be described in more detail with reference to the following examples and test examples. In the examples, "parts" means parts by weight.

Example 1 250 g of polyethylene beads were put into a speed mixer, and crotrimazole 2.6 was previously prepared while rotating.
g, 2.6 g of polyethylene glycol and 5.2 g of hydroxypropylcellulose were sprayed with a mixed solvent of 100 g of ethyl alcohol and 15 g of water to obtain a composite powder coated with polyethylene beads.

Example 2 300 g of silica beads were put into a fluidized bed granulator, and 150 g of ethyl alcohol in which 3.1 g of omoconazole, 3.1 g of isopropyl myristate, and 6.0 g of polyvinylpyrrolidone had been previously dissolved were sprayed while flowing. A composite powder coated with silica beads was obtained.

Example 3 250 g of polystyrene beads were charged into a fluidized bed granulator,
80 g of ethyl alcohol in which 5.5 g of miconazole nitrate, 5.5 g of polyethylene glycol and 11 g of hydroxypropyl cellulose were previously dissolved while flowing.
A mixed solvent of water and 50 g of water was sprayed to obtain a composite powder coated with polystyrene beads.

Example 4 250 g of silica beads were put into a fluidized bed granulator, and while being fluidized, 5.4 g of omoconazole, 5.4 g of polyethylene glycol and 10.9 g of hydroxypropyl cellulose were dissolved in 100 g of ethyl alcohol and 30 g of water. The mixed solvent was sprayed to obtain a composite powder coated with silica beads.

Comparative Example 1 1.4 g of omoconazole and 138.6 g of talc were mixed with a speed mixer to obtain a powder.

Test Example 1 Skin Permeation Test Using Hairless Mice Using Examples 2 and 4 of the present invention and Comparative Example 1, a hairless mouse skin permeation test was performed by the following method. The results are shown in FIG. (Test method) The exfoliated skin of the hairless mouse was mounted on the Franz diffusion cell with the exfoliated skin facing up on the horny layer side, and the specimen was administered on the skin on the donor layer side, and after 4, 8, 12, 24, 32, and 48 hours Drugs that permeate the respective receptor phases were quantified by liquid chromatography.

Test Example 2 Preparation Comparison by Scanning Electron Microscope Preparations were observed by a scanning electron microscope using Example 2 and Comparative Example 1 of the present invention. FIG. 2 shows an example of the present invention, and FIG. 3 shows a comparative example. As a result, it was found that in the comparative example, the talc was dispersed in an irregular shape, and the drug was sparsely dispersed without almost uniformly dispersing the powder with talc.
In contrast, embodiments of the present invention have been found to be uniformly coated around the core material with a composition comprising the drug and the base material, and to be spherical and aesthetically powdered, so that the distribution area of the drug is wide. did.

[0020]

As is evident from FIG. 1, Examples 2 and 4 of the present invention have a faster skin absorbability rise than Comparative Example 1 and show remarkable skin penetration. As described above, the preparation of the present invention has remarkable transdermal absorption properties, excellent preparation properties such as uniform adhesion action, body fluid absorption action, drug release action from a drug, and remarkable antibacterial action. It is useful as a drug as an agent.

[Brief description of the drawings]

FIG. 1 shows the results of a hairless mouse skin permeation test.

FIG. 2 shows a photograph of the particle structure of the preparation of the present invention by a scanning electron microscope.

FIG. 3 shows a photograph of the particle structure of a comparative preparation by a scanning electron microscope.

[Explanation of symbols]

 ○ Comparative Example 1 □ Example 2 △ Example 4

──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Sachi Shinmura 408-dashiro Tashiro-machi, Tosu City, Saga Prefecture Hisamitsu Pharmaceutical Co., Ltd. (56) References JP-A-61-215324 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 9 / 14,47 / 30 A61K 47 / 10,47 / 14

Claims (3)

(57) [Claims] 1. An inorganic or organic core substance having a particle size of 0.5 to 10 μm is added to an antibacterial agent 0.1 to 5% by weight, a water-soluble polymer 0.2 to 15% by weight, and a dissolving agent 0.1 to 10% by weight. 10% by weight
A composite powder antibacterial agent characterized by being coated with a composition containing 2. The composite according to claim 1, wherein the core material is selected from silica beads, polyethylene beads, nylon beads, silicon beads, poly (methyl methacrylate) beads, and polystyrene beads. Powder antibacterial agent. 3. An antimicrobial agent comprising croconazole hydrochloride, clotrimazole, isoconazole nitrate, econazole nitrate,
Sulconazole nitrate, thioconazole, tolnaftate, bifonazole, miconazole, omoconazole,
The composite powder antibacterial agent according to claim 1, wherein one or more types are selected from itraconazole.