JPS63109865A - Pullulan film preparation containing drug as effective component - Google Patents

Abstract

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

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a pullulan film preparation containing as an active ingredient a certain kind of sterilizing disinfectant for external skin, a treatment agent for parasitic skin diseases, and/or a dental or oral agent. Regarding.

More specifically, the film contains iodine, iodoform, povidone-iodine, hexachlorophene, resorcinol, acrinol, methylrosaniline chloride, benzethonium chloride, benzalkonium chloride, sodium lauryl sulfate, thimerosal, merculochrome, chlorhexidine gluconate, chlorhexidine hydrochloride, alkyl polyamino hydrochloride. The present invention relates to a pullulan film formulation containing one or more drugs selected from ethylglycine, clotrimazole, miconazole nitrate, econazole nitrate, domifuene bromide, and dequalinium chloride in a dissolved or uniformly dispersed state.

[Conventional technology]

Pullulan is made from partially hydrolyzed starch and is produced by Aureobasidium pullulans.
α-glucan is fermented and produced by A. ium pullulans), and its structure consists of maltotriose and α-glucan.
It is a linear neutral polysaccharide with -1,6 bonds. It is a tasteless, odorless, amorphous, non-crystalline white powder from the Song Dynasty.

Pullulan powder is water-soluble and has excellent adhesive strength, adhesive strength, and film forming properties. It is also possible to form a colorless and transparent film, which has excellent properties such as oxygen barrier properties, fragrance retention properties, and oil resistance.

Since pullulan is edible, many applications are being considered, mainly in the food field. For example, a film has been proposed in which a fine food powder or liquid having a wasabi-like taste or aroma is blended into a pullulan film. As for application in the pharmaceutical field, it has been proposed to use it as a base or binder for tablets for the purpose of sustained release, and to coat tablets with pullulan liquid. However, there has been no proposal or report on incorporating drugs directly into pullulan film, and the possibility of this is still unclear.

[Problems with conventional technology]

On the other hand, there have traditionally been emergency bandages for the purpose of protecting and sterilizing wounds, but those that actually contain drugs such as bactericides include gauze soaked with acrinol solution, benzalkonium chloride solution, or domifuene bromide. There was nothing other than some sterilizers pasted on adhesive tape. The reason for this is that the disinfectant uses air,
Many of them are unstable with respect to heat and origin, making them unsuitable for long-term storage at room temperature in an unsealed state.Additionally, it is difficult to control the drug content, persistence, and release during application. For example, it was difficult to implement the project.

Therefore, it is desired that an emergency adhesive bandage for the purpose of truly sterilizing the wound site be developed.

In addition, when preparing a sterilizing disinfectant for the purpose of disinfecting hands, skin, or medical equipment, measure the required amount of stock solution or powder from a container (bottle) immediately before use, and then add a certain amount of the stock solution or powder. The conventional method of diluting the disinfectant with water is that most sterilizing disinfectants must be stored in an airtight container protected from light.

This method was never satisfactory, as it was not only complicated to accurately measure a certain amount of stock solution, but also the bottle could be damaged, the volume could be lost during weighing, and clothing could be contaminated. .

[Means for solving problems]

The present inventors have conducted extensive studies with the aim of incorporating an effective amount of a sterilizing agent into a conventional emergency bandage in a stable form over a long period of time, and eliminating the complexity of preparing a sterilizing agent. As a result of repeated research, we thought that the above-mentioned problems could be solved by incorporating an effective or necessary amount of sterilizing disinfectant in a dissolved or uniformly dispersed state in the pullulan film, and we developed films for various sterilizing disinfectants. I tried to form a. Before conducting this study, we thought that all disinfectants would form a film without any problem, but contrary to our expectations, some of them were unable to form a film. For example, even with the same phenolic disinfectant, resorcinol or hexachlorophene, the drug and pullulan glue (pullulan paste dissolved in water to spread into a film) can be easily mixed and spread into a film. In the case of phenol and cresol, when the two were mixed, pullulan coagulated instantly and no film could be formed.

The present inventors identified a drug capable of forming a film from among commonly used disinfectants for external skin, therapeutic agents for parasitic skin diseases, and agents for dental and oral cavity use, and completed the present invention.

[Structure of the invention]

Therefore, the present invention includes iodine, iodoform,
Povidone-iodine, hexachlorophene, resorcinol, acrinol, methylrosaniline chloride, benzethonium chloride, benzalkonium chloride, sodium lauryl sulfate,
One or more drugs selected from thimerosal, mercurochrome, chlorhexidine gluconate, chlorhexidine hydrochloride, alkyl polyaminoethylglycine hydrochloride, clotrimazole, miconazole nitrate, econazole nitrate, domifuene bromide, and dequalinium chloride are dissolved or uniformly dispersed. The present invention relates to pullulan film formulations containing pullulan film.

Pullulan has an average molecular weight of about 5,000 to 1,000,
000, and several types are commercially available depending on the range of average molecular weight. The pullulan used in the present invention may have any molecular weight, but preferably has an average molecular weight of about 200,000 (commercially available from Hayashibara Shi, Ltd. under the trade name PI-20). By changing the molecular weight of pullulan, the dissolution rate of pullulan and, by extension, the elution rate of the drug can be changed. Generally, the smaller the average molecular weight, the faster the dissolution rate, and the larger the average molecular weight, the slower the dissolution rate. Moreover, several types of pullulan having different average molecular weights may be used in combination.

The drugs contained are (1) sterilizing disinfectants for the skin: iodine, iodoform, povidone-iodine, hexachlorophene, resorcinol, acrinol, methylrosaniline chloride, benzethonium chloride, benzalkonium chloride, sodium lauryl sulfate, thimerosal, mercurochrome, gluconic acid; Examples include chlorhexidine, chlorhexidine hydrochloride, and alkyl polyaminoethylglycine hydrochloride, but preferred examples include iodoform, povidone-iodine, hexachlorophene, acrinol, benzethonium chloride,
Benzalkonium chloride, chlorhexidine gluconate and alkyl polyaminoethylglycine hydrochloride, more preferably povidone iodine, benzalkonium chloride and chlorhexidine gluconate.

(2) Clotrimazole as a drug for parasitic skin diseases;
Miconazole nitrate and econazole nitrate are mentioned, both of which are preferred.

(3) Examples of dental and oral agents include domi7ene bromide and dequalinium chloride, both of which are preferred.

Furthermore, the pullulan film formulation of the present invention may contain other auxiliary drugs if desired. These drugs include local anesthetics, hemostatic agents, antihistamines, etc., but these are of course limited to those capable of forming a pullulan film.

The pullulan film formulation of the present invention may contain only one kind of the above-mentioned drug, or may contain a mixture of two or more kinds.

Further, the size, thickness, shape, and drug content can be arbitrarily set depending on the purpose of use, which will be described later.

Furthermore, a plasticizer such as glycerin, ethylene glycol, polyethylene glycol, propylene glycol, nrubitol, martinol, mannitol, etc. can be added to the pullulan film formulation of the present invention, if necessary.

The pullulan film formulation of the present invention is a sterilizing disinfectant for the purpose of (1) sterilizing and disinfecting trauma sites and treating diseases of the skin, mucous membranes, and oral cavity, or (2) sterilizing and disinfecting fingers, skin, medical tools, etc. Alternatively, it can be used as a patch.

In the case of (1), a pullulan film preparation applied to a wound or affected area (hereinafter referred to as a wound etc.) is rapidly softened by body sweat or body fluids, becomes more adhesive and adheres to the wound etc.

At the same time, pullulan dissolves and the drug contained in it leaches out and acts directly on wounds, etc. Although it is thought that this occurs in a very short time, sustained release can be achieved by changing the type of pullulan used. To use for the purpose of (1), the pullulan film preparation of the present invention can be applied directly to a wound, etc. and fixed with a bandage if necessary, or it can be prescribed in the form of a patch such as a so-called emergency bandage. More preferably, it is used as a patch. The patch is obtained by wrapping or pasting the present film preparation 1 of an appropriate size around all or part of a cushioning material 2 such as gauze or warp cloth as shown in the attached drawings. is attached to adhesive tape 3. The film preparation can be wrapped or pasted around the cushioning material in any shape, as long as the film preparation adheres to the wound, etc., and the film preparation and the cushioning material can be fixed to the wound, etc. with adhesive tape. It can be anything.

Specifically, for example, the film preparation is wrapped around the buffer material one or more times (see Figure 1), the film preparation is wrapped around the buffer material exactly one time (see Figure 1), and the film preparation is wrapped around the buffer material one time or less (see Figure 1). There are two types of cushioning material: one in which the cushioning material is wrapped around the adhesive tape (leaving only the part that comes into direct contact with the adhesive tape) (see Figure 3), and one in which the cushioning material is pasted on only one side (the side that comes into contact with the wound, etc.) (see Figure 4). can give.

Furthermore, the patch of the present invention does not require the method described above in which the present film preparation is first manufactured separately and then wrapped or pasted all or partially around the cushioning material. Spread the drug-containing pullulan glue obtained by the production method described below into a film on the contact surface) to directly form the film formulation, and attach the obtained buffer material with the film formulation to an adhesive tape. Also produced by the method. Although the desired effect can be obtained in either case, the preferred embodiment is the one shown in FIGS. 3 and 4. A perspective view of an example of a patch using the form shown in FIG. 3 is shown in FIGS. 5(1k) to 5(C). The adhesive tape serves to secure the film to the wound and protect the five openings. Also, the wound etc. are inside the vagina, directly? When the drug is in the nasal cavity, the film preparation can be rolled into a cylindrical shape and inserted directly into the receiving cavity. At this time, the film does not need to be removed after the procedure because it is dissolved throughout the baby by body fluids.

In the case of (2), the film preparation of an appropriate size containing an appropriate amount of sterilizing agent can be prepared, and the film can be diluted with the necessary amount of water before use. 1 is required.In addition, damage to the bottle and loss of contents (loss)
, you don't have to worry about contaminating your clothes.

The film added to a large amount of water instantly dissolves to provide a sterilization raft with a set concentration. Since pullulan water solution has a lower viscosity than other polysaccharides, the resulting sterilizing disinfectant does not have a slimy feel and can be used with exactly the same feeling as the same litter prepared by conventional methods.

The pullulan film formulation of the present invention can be produced by a known method, for example, the method described in JP-A No. 54-13565. That is, 2 parts and 4 parts of Japanese water are added to 1 part of pullulan powder, and the mixture is heated at 80 to 100 DEG C. for several hours and thoroughly kneaded. , the obtained paste-like pullulan was 35 to 4
Drug pre-dissolved in purified water after cooling to 5 °C;
Alternatively, if the target drug is insoluble in water, add the drug powder passed through a sieve as small as possible, stir and mix thoroughly to dissolve or disperse the drug uniformly in the pullulan, and then apply the drug-containing pullulan glue using the usual casting method. It can be manufactured by spreading it into a film.

〔effect〕

The pullulan film formulation of the present invention has the following effects.

(1) This preparation retains the excellent properties of pullulan film, such as oxygen barrier properties and fragrance retention, and therefore the drug will not be degraded or lost (it will remain stable for a long period of time).

(2) A constant drug content can be obtained accurately and easily, whether the drug is liquid or solid (crystal, powder).

(3) When applied to a wound, etc., it rapidly softens due to moisture such as body sweat and exudate, adheres closely to the wound, etc., and the drug is eluted and acts on the wound, etc.

(4) Since it is in the form of a film, it is much easier to handle than liquid agents and there is no need to worry about damage to the container.

(5) Pullulan is an edible natural carbohydrate derived from starch, and is non-toxic and non-irritating, making it an excellent base for film preparations for application to affected skin and mucous membranes.

(6) Compared to conventional water-soluble polymer film raw material compounds, pullulan has a relatively low viscosity when dissolved in water, so after applying the film formulation, it can be washed with water more easily than conventional films. Can be removed.

(7) When preparing a pullulan aqueous solution, it is less susceptible to negative effects, so a wide range of drugs can be included in the pullulan film formulation.

Hereinafter, the present invention will be explained in detail with reference to Examples and Experimental Examples.
The present invention is not limited to these examples.

Example 1 Pluruff C brand name, PI-20 (average molecular weight 200.
Add 75 f of sterile purified water at about 100°C to 25 f (manufactured by Hayashibara) and mix thoroughly, then boil to about 90°C.
Knead thoroughly while heating for 1 hour to make Pullulan glue 95? I got it. 93 ml of a 30.5% solution of povidone iodine was added to 9.5 tons of pullulan glue cooled to 40°C, thoroughly stirred and mixed, and then spread into a film with a thickness of about 20 μm by a casting method, and dried by heating by a conventional method to achieve the desired purpose. A povidone-iodine-containing pullulan film preparation was obtained.

Thereafter, in the same manner as in Example 1, pullulan film preparations of the present invention containing the drugs shown below were obtained.

Example 21 20f of pullulan glue (produced in Example 1) was added with 43 cm of benzalkonium chloride and chlorpheniramine maleate (
Add 1001r9 (antihistamine) and stir thoroughly to dissolve it, then add 250cm of ethyl aminobenzoate (local anesthetic) finely powdered with a milk wasp and stir thoroughly! @Made it muddy. The obtained drug-proprietary pullulan glue was applied to PET (
The mixture was spread on a polyester film by a casting method and dried by heating to obtain a pullulan film preparation with a thickness of about 60 μm.

Example 22 The pullulan film preparation obtained in Example 1 was
It was cut to the size of a 5m wing, wrapped in 13m x 25mz gauze, and attached to an appropriately sized single-sided adhesive tape to obtain an emergency bandage.

Experimental Example Antibacterial activity test of pullulan film preparation of the present invention 2.8 ■ of pullulan and povidone iodine were mixed in 1 ml from 05 ■ to 3.8
Pullulan films of the present invention were prepared containing 14 levels of pullulan up to (1), and their antibacterial activity was tested by a method similar to the Disk method. That is, the test bacteria include Elysia coli (Eachericht & Co11) 1.
Disk on a large plate using SCD agar medium (manufactured by Daiku Nutrient Chemical Co., Ltd.) using F, 0.12743.
A prototype film of 1 d in size was pasted on an agar plate in accordance with the Act, and its antibacterial activity was assayed (cultivation time was 20 hours).

As a result, in the case of povidone-iodine used in this experiment, the effect of inhibiting bacterial growth appeared only in the area where the film was applied.
Its bacteriostatic action is shown at a concentration of povidone-iodine of 0.54η/- or more, and its bactericidal action is shown at a concentration of 1-8"! / tr
It has been proven that this is shown at a concentration of i or higher.

[Brief explanation of the drawing]

Figures 1 to 4 are cross-sectional views showing an example of a method for covering a cushioning material with a film formulation when making an emergency bandage using the pullulan film formulation of the present invention, and Figure 5 (
e) to (e) are perspective views of the patch when the coating method shown in Fig. 3 is used; View from the side,
(C) is an enlarged view of the pullulan film portion. Codes in the figure: 1...°Drug-containing pullulan film preparation; 2...Buffer material; 3...Adhesive tape.

Claims (1)

[Claims] 1. Iodine, iodoform, povidone-iodine, hexachlorophene, resorcinol, acrinol,
Selected from methylrosaniline chloride, benzethonium chloride, benzalkonium chloride, sodium lauryl sulfate, thimerosal, markyurochrome, chlorhexidine gluconate, chlorhexidine hydrochloride, alkyl polyaminoethylglycine hydrochloride, clotrimazole, miconazole nitrate, econazole nitrate, domifuene bromide and dequalinium chloride A pullulan film preparation containing one or more drugs in a dissolved or uniformly dispersed state. 2. The pullulan film preparation according to claim 1, wherein the average molecular weight of pullulan is about 200,000. 3. Drugs include iodoform, povidone-iodine, hexachlorophene, acrinol, benzethonium chloride, benzalkonium chloride, chlorhexidine gluconate, alkylpolyaminoethylglycine hydrochloride, clotrimazole,
The pullulan film preparation according to claim 1 or 2, which is one or more drugs selected from miconazole nitrate, econazole nitrate, domifuene bromide, and dequalinium chloride. 4. One or two drugs selected from povidone iodine, benzalkonium chloride, and chlorhexidine gluconate
The pullulan film preparation according to claim 3, which is a drug for more than one species. 5. The pullulan film preparation according to claim 4, wherein the drug is povidone iodine. 6. Iodine, iodoform, povidone iodine, hexachlorophene, resorcinol, acrinol,
Methylrosaniline chloride, benzethonium chloride, benzalkonium chloride, sodium lauryl sulfate, thimerosal, makyurochrome, chlorhexidine gluconate,
A pullulan film preparation containing one or more drugs selected from chlorhexidine hydrochloride, alkyl polyaminoethylglycine hydrochloride, clotrimazole, miconazole nitrate, econazole nitrate, domifuene bromide, and dequalinium chloride in a dissolved or uniformly dispersed state. A patch consisting of cushioning material and adhesive tape. 7. Wrap the pullulan film preparation around the area where the cushioning material directly contacts the adhesive tape, or apply the pullulan film preparation only to the surface where the cushioning material comes into contact with the wound, etc., and then The patch according to claim 6, wherein the adhesive tape is affixed to an adhesive tape. 8. The drug is one or two selected from povidone iodine, benzalkonium chloride, and chlorhexidine gluconate.
8. The adhesive patch according to claim 6 or 7, which is a combination of more than one drug. 9. The adhesive patch according to claim 8, wherein the drug is povidone-iodine.