KR20110027434A

KR20110027434A - Composition for forming water-repellent film with sustained drug release ability

Info

Publication number: KR20110027434A
Application number: KR1020090085522A
Authority: KR
Inventors: 문주명; 백대헌
Original assignee: 보람제약주식회사
Priority date: 2009-09-10
Filing date: 2009-09-10
Publication date: 2011-03-16

Abstract

The present invention relates to a composition for forming a water-repellent film capable of sustained release of a drug, and more particularly, to form a gel by dissolving in a solvent, but after applying to a wound site, to form a water-repellent film, and after the film is formed, is adhesive The present invention relates to a composition for forming a water-repellent film capable of sustained release of a drug that does not fall off and maintains flexibility, protects a wound safely, and provides moisturizing power to a wound to enable rapid wound treatment.

The water-repellent film-forming composition according to the present invention can prevent the secondary infection by preventing the applied wound site from getting wet with water, and can maintain strong adhesiveness and flexibility even in the refractive and friction parts of the body, so that it can be used for a long time even with one application. If you want to re-apply, re-administration of the drug and repositioning of the film is possible only by re-coating without a separate film removal process, it is possible to control the long-term release of the drug.

Film Forming Polymer, Water Repellent Film, Volatile Organic Solvent, Plasticizer, Surfactant, Adhesive, Peelability, Flexibility, Sustained Release Drug Delivery, Gel

Description

Composition for Forming Water-repellent Film with Sustained Drug Release Ability}

Skin damaged by cuts, abrasions, burns is a wound recovery through tissue regeneration process, the exudates formed in the damaged area is hardened and then easily infected with pathogens may cause secondary inflammation.

The scab formed on the active part of the body is often cracked by the contraction and relaxation of the skin, friction with clothes, friction with external objects, and contaminated causes delayed wound healing and causes scarring even after complete cure.

Damaged skin is delayed in regenerating and repairing the skin if proper moisture environment is not maintained, and the scab of the wound area is isolated from normal skin by repeated contraction and relaxation, and the wound is spread, and inflammation is caused by secondary infection. Can lead to. Therefore, proper wound disinfection is required for wound protection and contamination prevention, and it must be protected from external physicochemical effects. For this reason, gel preparations applied to wounds must be able to maintain disinfection and prevent secondary infection, as well as provide breathability, adequate wet environment and continuous drug delivery to the wound.

Film forming polymers have traditionally been used primarily in the coating of tablets in the pharmaceutical arts. Polymer film formation used to protect tablets from the external environment (typically using HPMC), to protect drugs from gastric acid (typically HPMCP), or to control the dissolution rate (typically HPMC, methacrylate, etc.) I have a lot.

On the other hand, plasticizers (typically PEG) for imparting fracture stability of film formers have been widely used in traditional formulations. There are many examples using the characteristics of the film-forming agent used for the purpose of external application of the human body, for example, nail art, hydrogel (Hydrogel), a heating gel.

Skin coatings for the purpose of skin treatment include ointments, creams, gels, lotions, and the like as hydrogels. However, it is an ideal skin treatment gel for the purpose of treating wounds of the skin, protecting the skin from water and other contaminants, continually releasing the drug, resisting adhesion and human activity, and reinjecting the drug with reapplication only. It has not been technically completed yet.

A study on the film-forming base includes a Korean patent (1990-0005495) that produces a peelable nail enamel composition by combining ethyl cellulose (EC), acrylonitrile-butadiene-styrene copolymer, polybutene, and benton 27. As a nail makeup composition, it is durable, abrasion resistance, light resistance, and heat resistance, characterized by using nitrocellulose (pyoxylin) wetted with isopropanol and ethyl acetate, butyl acetate, amyl acetate, ethanol, butanol, isopropanol, toluene, etc. as a solvent. There is a Korean patent (1996-0004011) for nitrocellulose composition.

As a method for increasing skin applicability, abrasion resistance, durability, light resistance, etc. of the film, there is a Korean patent (1992-0002283) using nitrocellulose as a film base composition. It is difficult, and due to the low film flexibility is difficult to apply a wide range of skin. In addition, due to strong toxic volatile solvents such as toluene, benzene, chloroform and the like contained in the gel formulation, there is a limit to the application of the wound treatment by generating rash and toxicity of the wound and skin.

Film forming agents for transdermal application include Korean Patent (1998-076273) for breathable transparent film forming gel composition having high skin adhesion and film forming composition (WO 2002/55023) for treating nail and skin surface diseases. In the former case, a film forming treatment composition containing a film forming agent, a plasticizer and a volatile solvent was used, and an excipient capable of generating heat as a core technology for skin application was used. In the latter case, a hydrophilic and hydrophobic polymer was used as a film forming polymer. It is a gel composition mixed with water-repellent, the film is dissolved in high humidity and loses its elasticity or takes too much time to dry and there is a characteristic that difficult drug dissolution is difficult to apply a separate drug delivery system.

In the research of adhesive peeling agent that can transmit skin of drug (WO 2005/120473), in addition to using non-volatile solvent, we developed a drug that can transmit skin of drug using plasticizer, hydrophilic and hydrophobic polymer, etc. As a result, the film is soluble in water, so it is difficult to protect the wound in the underwater environment, and there is a disadvantage that additional contamination of the wound may occur.

Other researches on gels for skin application include Korea Utility Model (20-0422370), but this is related to the development of non-adhesive wound-coated dressings that can create a wet environment on the wounded area. The gel is only water repellent and has a disadvantage in that it is impossible to protect, apply and treat the wound for a long time due to the dissolution of the film in a high humidity environment.

Other gel formulations have been used in patches, dressings, films, gels, bands, packs, etc., but did not implement a water repellent film forming gel formulation capable of sustained release drug delivery.

Thus, the present inventors are applied to the wound to solve the problems presented in the prior art as described above to maintain a constant moisturizing and aeration environment, the wound is not wetted with water by the applied water-repellent film, even in a high temperature and high humidity environment Tackiness and flexibility are maintained so that it is not hard to fall off, so it is possible to bathe and swim, and re-application of drugs and repositioning of the film is possible only by reapplication without the need for separate film removal. Efforts have been made to prepare a water-repellent film-forming composition for wound treatment, which has led to the completion of the present invention.

After all, an object of the present invention is a water-repellent film-forming composition prepared using a water-repellent film-forming polymer, when applied to the wound site can form a water-repellent film to protect the wound even when exposed to water and drug delivery continuously to the wound site It is possible to provide a composition for forming a sustained release water repellent film.

In order to achieve the above object, the present invention provides a composition for forming a water-repellent film capable of sustained release of a drug comprising a hydrophobic water-repellent film-forming polymer, an oil component, a plasticizer, a surfactant, a hydrophilic polymer, distilled water and a pharmacologically active ingredient. to provide.

According to one embodiment of the invention, the hydrophobic water-repellent film-forming polymer should be soluble only in volatile organic solvents, the hydrophobic water-repellent film-forming polymer is poly D-lactide, poly L-lactide, poly DL-lock Selected from the group consisting of tide, polyglycolide, poly L-lactide glycolide copolymer, poly L-lactide glycolide copolymer, poly DL-lactide glycolide copolymer and poly DL-lactide caprolactone copolymer Group consisting of polyoxyethylene alkyl ethers such as at least one aliphatic polyester, cyclomethicone, diethylphthalate, dimethicone, ethylcellulose, hydrophobic solvent soluble polymethacrylate, taxophore, polyvinyl acetate phthalate and shellac It may be one or a mixture of two or more selected from.

The hydrophobic water repellent film-forming polymer may be mixed to be 1 to 30% by weight in the total composition. Mixing less than 1% by weight results in a negligible effect for film formation, and mixing more than 30% by weight makes it difficult to make the composition into a gel formulation.

The hydrophobic water-repellent film-forming polymer is capable of dissolving only in volatile organic solvents, and thus re-administration of the drug and re-arrangement of the film by reapplication without a separate film removal, and can be easily removed when removing the film. Can be obtained.

Volatile organic solvents for the preparation of water repellent film formation include one or two of acetone, chloroform, ethyl acetate, methylene chloride, tetrahydrofuran, isopropyl myristate, isopropyl palmitate, mineral oil, ether, ethanol, methanol, toluene, and the like. A mixture of more than one species can be selected, but it is more preferable to have a skin toxicity and allergic reaction, so that the stability of the skin is secured, the smell is weak, the toxicity is low to the skin and the respiratory system, and the volatilization rate is high. Do.

In one embodiment of the present invention, the plasticizer is acetyltributyl citrate, acetyltriethyl citrate, chlorobutanol, dibutylphthalate, diethylbutyrate, dimethylphthalate, glycerin monostearate, lanolin alcohol, polyethylene glycol, Synthetic oils selected from the group consisting of poly vinyl acetate phthalate, propylene glycol, tributyl citrate, triethanolamine and triethyl citrate; At least one vegetable oil selected from the group consisting of almond oil, castor oil, hydrated castor oil, corn oil, cotton seed oil, lecithin, olive oil, peanut oil, soybean oil, sunflower seed oil and hydrated vegetable oil; At least one animal oil selected from the group consisting of tocopherol, lanolin and lanolin alcohols; At least one mineral oil selected from the group consisting of mineral oil, liquid paraffin and petrolatum; And it may be one or a mixture of two or more selected from the group consisting of ethanolamine.

In addition, the plasticizer imparts adhesiveness, flexibility, peelability to the water repellent film, and serves to maintain the physical properties of the film to enable sustained release of the drug by keeping the film stretchable for a long time, the content of the hydrophobic water repellent film It is preferable that it is 50-100 weight part with respect to 100 weight part of forming polymers, since the addition of the content below it is inferior to the flexibility, and when more content is added, stickiness increases and it is not preferable.

In the present invention, a surfactant for stabilizing the W / O emulsion between the polymer film and the drug is mixed. The surfactant is glyceryl monoorate, wax, sorbitan ester (span), polyoxyethylene alkyl ether, benzethonium chloride. It may be one or a mixture of two or more selected from the group consisting of lauryl acid, polysorbate, triethyl citrate, cetamide, sodium lauryl sulfate.

In addition, the surfactant may add 0.1 to 5% by weight of the total composition. The addition of less than 0.1% by weight is negligible and the addition of more than 5% by weight makes it difficult to make the composition into a gel formulation.

It is most effective to mix the surfactant at 0.5 wt% or less in the total composition, because at higher concentrations, the stickiness may be increased or the drying of the film may be time-consuming and wear resistance and strength may be reduced.

In one embodiment of the present invention, the hydrophilic polymer is poloxamer, hydroxypropyl cellulose, propylene glycol, polyethylene oxide, polyethylene glycol (PEG), polycarbophil, carbomer, hydroxyethyl cellulose, hypromellose, poly It may be one or a mixture of two or more selected from the group consisting of vinyl alcohol, povidone, ammonium alginate, cyclomethicone and xanthan gum.

In addition, the hydrophilic polymer is to be added as a thickening / moisturizer for improving the firmness and imparting peelability through the continuous drug release to the skin of the water-repellent film and maintaining humidity, 0.1 to 10% by weight of the total composition can be added have. When the hydrophilic polymer is added less than 0.1% by weight, the effect of adding the hydrophilic polymer is hardly exhibited, and when the hydrophilic polymer is added more than 10% by weight, it may impede the formation of a water repellent film.

It is most effective to add the hydrophilic polymer at 1.4 wt% or less in the total composition, since the stickiness of the film increases at higher concentrations and the water absorption in the underwater environment may increase, causing a whitish change or an increase in viscosity.

In the present invention, purified water may be included for dissolving the drug as well as for dissolving plasticizers and solvents for W / O emulsions and for releasing the initial drug from the hydrophobic film. It is preferable to include the purified water to be 0.1 to 10% by weight of the total composition when considering the adhesive strength, tensile strength and the like of the total composition.

According to one embodiment of the present invention, the composition is a non-controlling agent for relieving irritation when applying the skin further 1 to 50% by weight benzyl alcohol, 0.1 to 0.7% by weight chlorobutanol or 0.1 to 0.5% by weight lidocaine It may include.

According to another aspect of the present invention, a pharmacologically active ingredient, a plasticizer including an emulsion component, a surfactant and a hydrophilic polymer are dissolved in water, mixed and heated to prepare an emulsion with a high speed homogenizer; Separately dissolving the hydrophobic water repellent film forming polymer in a volatile organic solvent; And adding a volatile organic solvent in which the film-forming polymer is dissolved, and mixing the prepared emulsion solution, thereby providing a method of preparing a film-forming composition capable of sustained release of a drug.

The composition for forming a water-repellent film capable of sustained release of the drug formed by the present invention can provide a skin-binding force by itself when forming a water-repellent film to protect the skin cut surface, but as a pharmacologically active drug applicable for more effective wound treatment Various antibiotics, antifungal agents, antiviral agents, scar treatment agents, wound treatment agents and the like can be used in combination of one or more.

The water-repellent film formed by the composition according to the present invention can be free from secondary contamination without any disinfection when applied to the wound, it can be maintained firmness and flexibility even in the active skin shrinkage and relaxation. In addition, the film is safely maintained even at high humidity and temperature, so that the wound on the film-coated area does not get wet with water, so showering or underwater work is possible, and the humidity of the wound area can be kept constant so that quick wound recovery is possible. Application can protect the wound for a long time.

The water-repellent film according to the present invention can apply an emulsion technique capable of different hydrophilic-hydrophobic interactions for sustained release drug delivery that enables continuous drug release with flexibility. In more detail, the emulsion plasticizer and the solubilized drug form W / O emulsion again after evaporation of the volatile solvent, and the drug is continuously injected into the skin by the interaction of hydrophilic emulsion and hydrophobic film for a long time. It provides a composition capable of forming a water-repellent film having a sustained release drug release characteristics to be delivered.

When explaining the characteristics of the present invention in more detail, the film-forming base can be dissolved only in the volatile organic solvent to form a gel, the wound can be disinfected by the volatile solvent contained in the gel, the film formed after the volatilization of the organic solvent A water-repellent film forming composition which exhibits water repellency and is capable of continuously drug release into the skin by hydrophobic interaction between skin lipid layers by water-in-oil (W / O) emulsion between a drug-encapsable polymer film and a drug To provide.

In particular, since the W / O emulsion technique is used in the composition of the present invention, these drugs may have an advantage that they can be selected as long as they dissolve in both water-soluble and volatile organic solvents.

The composition of the present invention exhibits adhesion, peelability and flexibility by plasticizers and surfactants, and the formed water-repellent film protects the wound from secondary contamination, and the wound applied with the film does not get wet with water. Possible water repellent film forming compositions.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these Examples are only for illustrating the present invention, and the scope of the present invention will not be construed as being limited by these Examples.

Property / Drug Release Test Method of Film

The physical properties of the water-repellent film formed by the present invention were analyzed by the following terms, and the analysis of release of the drug from the film was carried out by applying a gel containing the drug to a plastic film to a thickness of 1 mm and drying it, then width x length (2 x 2 cm). The elution of the drug was confirmed while maintaining the rotational speed of the paddle at a speed of 50 rpm per minute at 37 ± 0.5 ° C using an eluent (Varian VK7000, USA) in a 500 ml eluate to which 1 wt% Tween 80 was added. The dissolution analysis of sodium fucidinate according to an embodiment of the present invention was carried out using a high pressure liquid chromatography at 235 nm using a mobile phase containing acetonitrile: methanol: phosphoric acid according to the Korean Pharmacopeia analysis method and quantified by using fusidic acid as a standard. It was.

<Control>

In order to examine the characteristics of the present invention, a gel was prepared by dissolving fusidic acid (or sodium fusidate) in ethylcellulose gel and nitrocellulose gel which are basic water repellent film formations.

Comparative Example 1

14 g of ethyl cellulose was dissolved in 84 g of ethanol, and 2 g of fusidic acid was added thereto, and the mixture was dissolved and mixed to obtain 100 g of a control example 1 gel.

ingredient Content (g) Ethyl cellulose 14.0 ethanol 84.0 Fushidinic acid (sodium) 2.0 system 100.0

The elution rate of fusidic acid for 2 hours when the gel thus prepared was tested according to the above dissolution test was 1.2%. After applying gel to the finger joints, the organic solvent was volatilized and then the joint movement was performed. After 3-4 times, breakage of the film was observed. Separation from the skin also occurred easily. Repeated application and drying two to three times to increase the thickness of the film and then separated from the skin when the film was broken and did not separate cleanly.

Control 2

ingredient Content (g) Nitrocellulose 18.0 toluene 25.0 Butyl acetate 27.0 Ethyl acetate 10.0 Acetone 8.0 Butyl phthalate 10.0 Fucidinic acid 2.0 system 100.0

Toluene, acetone, butyl acetate, ethyl acetate, and butyl phthalate were added to 18 g of nitro cellulose, followed by mixing. Then, 2 g of fusidic acid was added to make 100 g to obtain a control example 2 gel.

The elution rate of fusidic acid for 2 hours when the gel thus prepared was tested according to the above dissolution test was 0.2%. In addition, a gel was applied to the finger joints to form a film, and then joint motion was performed. However, after an average of four or five times, the film cracked.

Example 1: Change of Physical Properties of Film by Addition of Plasticizer

In order to confirm the change in physical properties of the film according to the addition of the plasticizer, the composition of Comparative Example 1 (ethyl cellulose gel) was used, and as the plasticizer, vegetable oil, soybean oil and castor oil were changed to 50, 75, and 100 parts by weight of 100 parts by weight of ethyl cellulose. As a plasticizer, ranulin, liquid paraffin, petrolatum, mono / di / triethanolamine, and polyoxy ethylene hydrogenated castor oil were prepared at 75% by weight of ethylcellulose, respectively. The ethanol solvent by the amount of plasticizer weight increase was reduced to obtain 100 g of each sample, which was subjected to the flexibility test and the abrasion resistance test.

Ingredient combination Production Example 1
(g) Preparation Example 2
(g) Preparation Example 3
(g) Preparation Example 4
(g) Preparation Example 5
(g) Preparation Example 6
(g) Preparation Example 7
(g) Preparation Example 8
(g) Preparation Example 9
(g) Preparation Example 10
(g) Preparation Example 11
(g) Ethyl cellulose 14.0 14.0 14.0 14.0 14.0 14.0 14.0 14.0 14.0 14.0 14.0 ethanol 77.0 73.5 70.0 77.0 73.5 70.0 73.5 73.5 73.5 73.5 73.5 Plasticizer Soybean oil 7.0 10.5 14.0 - - - - - - - - Castor oil - - - 7.0 10.5 14.0 - - - - - Ranulin - - - - - - 10.5 - - - - Liquid paraffin - - - - - - - 10.5 - - - Vaseline - - - - - - - - 10.5 - - Mono / di / triethanolamine - - - - - - - - - 10.5 - Polyoxy Ethylene Hydrogenated Castor Oil - - - - - - - - - - 10.5 Fushidinic acid (sodium) 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 system 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0

Test Example 1: flexibility test

The gel prepared according to the combination of Table 3 was applied to the finger joints to form a film, and then joint movement was performed to investigate how many times the film was cracked.

The results showed that mineral oils lacked lanulin 5 times, liquid paraffin 3 times and petrolatum 6 times. On the other hand, fatty acid amines such as mono / di / triethanolamine were tolerated up to 22 to 25 times, and polyoxy ethylene hydrogenated castor oil (cramoper), which is a castor oil variant, was also inflexible about 7 times. Soybean oil in vegetable oil showed excellent flexibility withstanding 50 to 48 times, 75 to 78 times, and 100 to 120 times the weight of ethyl cellulose. Castor oil survived 200 times in all 50% to 100% of ethyl cellulose. Less than that, the composition is less flexible, and more than that, the stickiness is increased, which is not preferable.

Test Example 2: wear resistance test

The film gels prepared in Preparation Examples 1 to 11 and Comparative Examples 1 and 2 of Example 1 were applied to a thickness of 1 mm thick x 4 cm on transparent vinyl, and then dried at room temperature for 2 hours to form a film. The film-coated transparent vinyl was attached to a swirler, and then measured according to the abrasion resistance test method in which 1 mm diameter sand was put on and left to vibrate for 4 hours.

After 10 hours after the experiment, 20% of Control Example 2 (nitrocellulose gel), 25% of Control Example 1 (ethylcellulose gel), and 8% of Preparation Example 5 (ethylcellulose gel + castor oil) The weight was reduced, and in the film forming composition (ethyl cellulose gel + castor oil + surfactant + hydrophilic polymer) containing all the plasticizer, surfactant, and hydrophilic polymer to be finally prepared in the present invention, a decrease of 8% was observed ( 1).

From the above results, it was confirmed that the wear progressed more quickly in the films of the hardness-hardened Comparative Examples 1 and 2 without the addition of the plasticizer, and the relatively mild wear was observed in the film to which the plasticizer was added to the moisture and flexibility. Could.

Example 2: Change of Physical Properties of Film by Addition of Surfactant

In order to confirm the change in the physical properties of the film according to the addition of the surfactant, based on the composition of Comparative Example 1 (ethyl cellulose gel), by adding Span 60 or glyceryl monoorate as a surfactant, castor oil as a plasticizer, distilled water as a film type A gel was prepared. Table 4 shows the contents of the preparation example in which the control example and the surfactant were added.

ingredient Control
3 (g) Production Example 12 (g) Preparation Example 13 (g) Production Example 14 g Production Example 15 g Production Example 16 g Production Example 17 (g) Ethyl cellulose 14.0 14.0 14.0 14.0 14.0 14.0 14.0 Sodium fucidinate 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Distilled water 4.0 4.0 4.0 4.0 4.0 4.0 4.0 Castor oil 11.0 11.0 11.0 11.0 11 11.0 11.0 Span60 0.0 0.3 0.4 0.5 0.0 0.0 0.0 Glyceryl Monoate 0.0 0.0 0.0 0.0 0.5 1.0 1.5 ethanol 69.0 68.7 68.6 68.5 68.5 68.0 67.5 Drug Release (%) 1 hours 0.98 3.4 5.4 7.8 5.2 7.3 9.2 2 hours 1.78 7.2 11.5 14.3 10.7 15.9 18.7

As a result of examining the physical properties of the film according to the optimal concentration of the selected span 60 of the surfactant for drug release of the present invention, the peelability, tackiness and flexibility in the sample group added 0.5 wt. It was found to be extremely high, but at higher concentrations, the stickiness was increased, and it took a long time to dry the film and showed a property that the wear resistance was lowered.

In the case of glyceryl monooleate, as the content increased, it helped to increase the dissolution rate, but it was shown to weaken the film strength.

Example 3: Change of Physical Properties of Film by Addition of Hydrophilic Polymer

In order to increase the thickness of the film and improve drug release, hydroxypropyl cellulose (HPC), which is a hydrophilic polymer, was added according to the concentration, and drug release was compared.

In Comparative Example 3 of Example 2, the release rate of the drug was investigated while increasing the HPC by the following weight% (reduced ethanol by the increase). In Table 5 below, the HPC is 0.7, 1.4, 2.1 wt% in the total composition.

In order to investigate the complex action of the HPC and the surfactant and the like as shown in Table 5, the physical properties and dissolution rate were investigated.

ingredient Control 3 (g) Production Example 18 (g) Production Example 19 (g) Production Example 20 g Ethyl cellulose 14.0 14.0 14.0 14.0 Sodium fucidinate 2.0 2.0 2.0 2.0 HPC 0.0 0.7 1.4 2.1 Distilled water 4.0 4.0 4.0 4.0 Castor oil 11.0 11.0 11.0 11.0 Span60 0.0 0.5 0.5 0.5 Glyceryl Monoate 0.0 1.0 1.0 1.0 ethanol 69.0 66.8 66.1 65.4 Drug Release (%) 1 hours 0.98 6.4 15.3 25.9 2 hours 1.78 13.5 25.7 43.8

Gel type Discharge time ( hr ) Drug Release Rate (%) Ethyl Cellulose Gel (Control Example 3) One 1.3 2 2.6 HPC 0.7% by weight gel (Preparation 18) One 1.9 2 3.5 HPC 1.4 wt% gel (Preparation 19) One 4.17 2 5.70 HPC 2.1 wt% gel (Preparation 20) One 5.01 2 6.87

As can be seen in Table 6, as the content of the HPC increases it was found that the drug release rate and the sustainability over time.

As a result of examining the effect of the HPC addition of the film-forming gel, it can be seen that as the amount increases, the dissolution rate has a good effect. In terms of physical properties, it showed the best physical properties of the film at 1.4 wt%, but at higher concentrations, the stickiness of the film was greatly increased, and it was observed that the water was absorbed in the water environment due to the high water absorption. It showed the property that the skin applicability is lowered.

Example 4: drug release, The tensile strength Adhesion Test

In order to confirm the drug release of the water-repellent film-forming composition comprising all of the plasticizer, the surfactant and the hydrophilic polymer by the present invention, after forming the film-forming composition by the formulation and the control agent of Table 7 below to form a film and dried Drug release test, tensile strength test, adhesion test was carried out.

ingredient Gel composition (unit: g) Control agent A Control agent B Control agent C Formulation-1 Formulation-2 Formulation-3 Ethyl cellulose 14.0 14.0 - 14.0 14.0 14.0 ethanol 80.0 69.0 - 66.8 66.1 65.4 HPC - - - 0.7 1.4 2.1 Castor oil - 11.0 - 11.0 11.0 11.0 Span 60 - - - 0.5 0.5 0.5 Glyceryl Monoate - - - 1.0 0.1 1.0 Sodium fucidinate 2.0 2.0 - 2.0 2.0 2.0 Purified water 4.0 4.0 - 4.0 4.0 4.0 Nitrocellulose - - 18.0 - - - toluene - - 25.0 - - - Butyl acetate - - 27.0 - - - Ethyl acetate - - 10.0 - - - Acetone - - 10.0 - - - Sodium phthalate - - 10.0 - - - system 100

Drug release test

The drug release of the concentration change of the water-repellent film-forming gel of the present invention was confirmed for 24 hours. As a result, HPC as a hydrophilic polymer and glyceryl monoorate and Span 60 as a surfactant were added. The drug dissolution rate was up to 5-16 times higher than for the formulations (Controls A-B) (FIG. 2).

The tensile strength exam

According to the tensile strength test clause of the band-aid specified in [Korean Pharmacopoeia], it was applied to a phenolic resin test plate with a thickness of 1 mm, width 12 mm and length of about 100 mm, and dried at 37 ° C. for 2 hours, followed by a tensile tester ( Using Aiko Machinery Co., Ltd., Japan, Model 1308), the gage distance is set to 150 mm and clamped with a clamp of 25 mm width and pulled at a speed of 240 mm for 1 minute to measure the maximum load until cutting. (FIG. 3)

Tensile strength was measured by comparing the ethyl cellulose gel film (Fig. 3a) added only castor oil as a plasticizer and the ethyl cellulose gel film (Fig. 3b) according to the present invention to which both castor oil, surfactant and hydrophilic polymer were added.

As a result, when only castor oil was added to ethyl cellulose gel, it was measured at a maximum of 1.3 kgf, and 8 seconds after the measurement, the film was torn (Figure 3a). In addition, in case of only castor oil, the load was unevenly distributed according to the tensile strength applied to the film, and the steep curve was inclined. This shows a steep curve due to the hardness (hardness) of the film when only castor oil is contained in the ethyl cellulose gel, whereas the film gel to which the plasticizer, the surfactant, and the hydrophilic polymer is added according to the present invention is a plasticizer, surfactant, and hydrophilicity. As a result of the increased flexibility of the film due to the polymer showed a slope and tensile strength (up to 0.95 kfg) of the gentle tensile curve (Fig. 3b).

In addition, the film was crushed after 8 seconds when only castor oil was added in the distribution of the time required to measure the tensile strength (FIG. 3a), but in the case of a gel film containing a plasticizer, a surfactant, and a hydrophilic polymer, the film was released after a maximum of 10 seconds. It showed a tendency to crush (Fig. 3b).

Through the above results, it can be seen that the film gel according to the present invention has greatly improved the flexibility of the film by the plasticizer, the surfactant and the hydrophilic polymer.

Adhesion test

The adhesion test of the film was carried out by slightly changing the adhesive test standards of the band-aids specified in the Test Method Standard Notice (2008-56) of the Korea Food and Drug Administration and the [Korean Pharmacopoeia].

The detailed method was to use a phenolic resin test plate and roughen the surface using sandpaper (model number 80) to create an environment similar to human skin, and apply a 12 mm x 100 mm width gel to 1 mm thickness. After drying for 2 hours at room temperature, the upper and lower parts of the film were fixed to the device using a tensile tester (Aiko Machinery Co., Ltd., Japan, Model 1308) at a 90 degree angle, and pulled at a speed of 240 mm for 1 minute to pull out the film. (For reference, the adhesive test criteria according to the Korean Pharmacopoeia indicate that the patch and the cataplasma agent are 42 g or more per 12 mm in width.)

Adhesion of the film according to the present invention is a film according to the control agent A of Table 7 because the flexibility of the film is very weak, the film is irregularly crushed, it was impossible to measure the adhesion (Fig. 4a), the case of adding castor oil The film according to Control B of Table 7 was measured up to 0.55 g (FIG. 4B). Meanwhile, the adhesive strength of the film gel according to the present invention including castor oil, a surfactant, and a hydrophilic polymer as a plasticizer was 0.46 to 0.47 g at maximum, which did not show a big difference from the control agent B. (FIG. 4C).

These results show that the plasticizer, surfactant, and hydrophilic polymer increase the flexibility, abrasion resistance, and tackiness of the film compared to the ethyl cellulose single film, thereby obtaining a water-repellent film-forming gel capable of sustained sustained release of the drug.

As confirmed through the above embodiment, the present invention provides a water-repellent film composition through the W / O emulsion to enable sustained release of the drug by hydrophobic interaction between the skin lipid layer, adhesion of the film by the plasticizer and the surfactant And it can be used as a new drug delivery agent to secure a film manufacturing gel that can be more secure wound protection and treatment due to the strong tensile strength maintenance effect.

In addition, the water-repellent film gel according to the present invention can prevent the secondary infection by not wet the applied wound area, and can maintain a strong adhesiveness and flexibility even in the refractive and friction parts of the body for a long time even with a single application If you want to re-apply, re-application of the drug and repositioning of the film is possible only by re-coating without separate film removal process, so it is possible to control the long-term release of the drug.

The specific parts of the present invention have been described in detail above, and it is apparent to those skilled in the art that such specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

1 is a wear resistance by comparing the ethyl cellulose gel film (Fig. 1a) added only castor oil as a plasticizer and the ethyl cellulose gel film (Fig. 1b) according to the present invention to which both castor oil, surfactant and hydrophilic polymers are added A graph showing the test results.

Figure 2 is a graph showing the drug dissolution rate of the composition of the control agent A to B and the formulations 1 to 3 according to Table 7.

3 is a tensile strength is measured by comparing the ethyl cellulose gel film (Fig. 3a) added only castor oil as a plasticizer and the ethyl cellulose gel film (Fig. 3b) according to the present invention added both castor oil, surfactant and hydrophilic polymer One graph.

FIG. 4 includes the film according to the control agent A of Table 7 (FIG. 4A), the film according to the control agent B of the Table 7 when castor oil is added (FIG. 4B), and the plasticizer includes castor oil, the surfactant, and the hydrophilic polymer. It is a graph which measured and showed the adhesive force of the film gel (FIG. 4C) to make.

Claims

A composition for forming a water repellent film capable of sustained release of a drug comprising a hydrophobic water repellent film forming polymer, a plasticizer containing an emulsion, a surfactant, a hydrophilic polymer and a pharmacologically active ingredient.

According to claim 1, wherein the hydrophobic water-repellent film-forming polymer is a composition for forming a water-release film capable of sustained release of the drug, characterized in that the soluble in the volatile organic solvent.

The method according to claim 2, wherein the hydrophobic water repellent film forming polymer is polyD-lactide, poly L-lactide, poly DL-lactide, polyglycolide, poly L-lactide glycolide copolymer, poly L-lactide At least one aliphatic polyester, cyclomethicone, diethylphthalate, dimethicone, ethyl selected from the group consisting of glycolide copolymers, poly DL-lactide glycolide copolymers and poly DL-lactide caprolactone copolymers A composition for forming a sustained-release water repellent film, wherein the drug is one or two or more selected from the group consisting of cellulose, hydrophobic solvent-soluble polymethacrylate, polyoxyethylene alkyl ether, polyvinyl acetate phthalate, and shellac. .

The method of claim 2, wherein the organic solvent for dissolving the hydrophobic water-repellent film-forming polymer is acetone, chloroform, ethyl acetate, petylene chloride, tetrahydrofuran, isopropyl myristate, isopropyl palmitate, mineral oil, ether, A composition for forming a water-repellent film capable of sustained release of a drug, characterized in that one or two or more mixtures selected from the group consisting of ethanol, methanol and toluene.

The method of claim 1, wherein the plasticizer is acetyl tributyl citrate, acetyl triethyl citrate, chlorobutanol, dibutyl phthalate, diethyl butyrate, dimethyl phthalate, glycerin monostearate, lanolin alcohol, polyethylene glycol, polyvinyl At least one synthetic oil selected from the group consisting of acetate phthalate, propylene glycol, tributyl citrate, triethanolamine and triethyl citrate; At least one vegetable oil selected from the group consisting of almond oil, castor oil, hydrated castor oil, corn oil, cotton seed oil, lecithin, olive oil, peanut oil, soybean oil, sunflower seed oil and hydrated vegetable oil; At least one animal oil selected from the group consisting of tocopherol, lanolin and lanolin alcohols; At least one mineral oil selected from the group consisting of mineral oil, liquid paraffin and petrolatum; And ethanolamine, and a composition for forming a water-repellent film capable of sustained release of a drug, characterized in that one or two or more mixtures selected from the group consisting of ethanolamine.

According to claim 1, wherein the content of the plasticizer is a composition for forming a slow release water-repellent film, characterized in that 50 to 100 parts by weight relative to 100 parts by weight of the hydrophobic water-repellent film-forming polymer.

The method of claim 1, wherein the surfactant is glyceryl monoorate, wax, sorbitan ester (span), polyoxyethylene alkyl ether, benzetonium chloride, lauryl acid, polysorbate, triethyl citrate, celima A composition for forming a water-repellent film capable of sustained release of a drug, characterized in that one or a mixture of two or more selected from the group consisting of id and sodium lauryl sulfate.

According to claim 1, wherein the surfactant is a composition for forming a water-repellent film capable of sustained release of the drug, characterized in that the addition of 0.1 to 5% by weight of the total composition.

The method of claim 1, wherein the hydrophilic polymer is poloxamer, hydroxypropyl cellulose, propylene glycol, polyethylene oxide, polyethylene glycol (PEG), polycarbophil, carbomer, hydroxyethyl cellulose, hypromellose, polyvinyl alcohol, Povidone, ammonium alginate, cyclomethicone and xanthan gum is a composition for forming a water-repellent film capable of sustained release of the drug, characterized in that one or two or more selected from the group consisting of.

According to claim 1, wherein the hydrophilic polymer is a composition for forming a water-repellent film capable of sustained release of the drug, characterized in that the addition of 0.1 to 10% by weight of the total composition.

The method of claim 1, wherein the purified water is a composition for forming a water-repellent film capable of sustained release, characterized in that it further comprises 0.1 to 10% by weight of the total composition weight.

The method of claim 1, wherein the composition further comprises 1 to 50% by weight benzyl alcohol, 0.1 to 0.7% by weight chlorobutanol or 0.1 to 0.5% by weight lidocaine in the total composition as a pain-free to relieve irritation during skin coating A composition for forming a water repellent film capable of sustained release of the drug.

The composition of claim 1, wherein the pharmacologically active ingredient is selected from the group consisting of antibiotics, antifungal agents, antiviral agents, scar treatment agents, and wound treatment agents.

Dissolving and mixing the pharmacologically active ingredient, the plasticizer including the emulsion component, the surfactant and the hydrophilic polymer in water, followed by heating and preparing an emulsion with a high speed homogenizer;

Separately dissolving the hydrophobic water repellent film forming polymer in a volatile organic solvent; And

Method for producing a film-forming composition capable of sustained release of the drug comprising the step of adding and mixing the volatile organic solvent in which the film-forming polymer is dissolved in the prepared emulsion solution.