KR101462018B1 - Orally Disintegrating Film Formulation Containing Entecavir - Google Patents

Abstract

Disclosed is a film preparation for treating hepatitis B comprising entecavir, which is a drug component of hepatitis B therapeutic agent, and discloses an enteric-coated oral disintegrating film preparation which is rapidly dissolved in the oral cavity and can be taken without drinking water .

Description

≪ Desc / Clms Page number 1 > Orally Disintegrating Film Formulation Containing Entecavir &

The present invention relates to an oral disintegrating film preparation containing entecavir, which is a therapeutic agent for hepatitis B as an active ingredient.

Entecavir is an antiviral agent developed by BMS (Bristol-Myers Squibb) for hepatitis B virus treatment. Entecavir is administered in a dose of 0.5 mg to 1.0 mg per day, and is commercially available in the form of tablets and syrups for these unit doses. However, such formulations such as tablets and syrups are inconvenient to be swallowed whole with an appropriate amount of water to deliver the drug, or taken at a constant dose (10 ml once in the case of syrup) while being carried. In addition, these formulations are susceptible to throat or discomfort of the esophagus when swallowing the drug, and are difficult to repeatedly take by patients such as elderly and pediatric patients who are difficult to take large amounts of formulations. In particular, since the hepatitis B therapeutic agent should be always carried and taken at a certain time, there is a problem that the administration of the therapeutic agent may be restricted depending on the availability of the drinking water at a specific time and place.

In the treatment of hepatitis B, the therapeutic agent has the risk of leading to liver fibrosis, cirrhosis, liver cancer, and ultimately death if not taken steadily. In addition to regular use of hepatitis treatment for the treatment of hepatitis B To 5 years of long-term treatment. Therefore, it is preferable that the hepatitis B therapeutic agent is a film preparation which can contain a therapeutically effective amount of hepatitis B therapeutic agent, and which can be rapidly disintegrated in the oral cavity so that it can be easily taken without the use of drinking water. Particularly, in patients who need to take drugs for a long period of time, the hepatitis B therapeutic agent is preferably a film preparation that can increase the patient's compliance with medication.

Conventionally, a technology related to a film preparation has been disclosed in Korean Patent Application No. 2011-0075179, but there has not yet been developed an oral film preparation containing a hepatitis B therapeutic drug.

It is an object of the present invention to provide a film preparation containing entecavir, which is a hepatitis B therapeutic drug component, and also to dissolve rapidly in the oral cavity in oral cavity.

The entecavir-containing film preparation according to the present invention is characterized by containing entecavir as an active ingredient. At this time, the entecavir-containing film preparation contains 0.001 to 30% by weight, preferably 0.1 to 12% by weight, and more preferably 0.4 to 12% by weight of entecavir based on 100% by weight of the entecavir- 5.0% by weight.

In addition, the entecavir-containing film preparation may include at least three components selected from plasticizers, sweeteners, flavors, taste-masking agents, acupressure stimulants, surfactants, pigments and preservatives together with the film forming agent.

The film forming agent may be selected from the group consisting of pullulan, starch, modified starch, pregelatinized starch, gelatin, pectin, sodium alginate, maltodextrin, polymerized rosin, hydroxypropylmethylcellulose (hypromellose), hydroxypropylcellulose, Low-substituted hydroxypropylcellulose, hydroxymethylcellulose, methylcellulose, sodium carboxymethylcellulose, colicote, eudragit, polyethylene oxide, polyvinylpyrrolidone, polyvinyl alcohol, hyaluronic acid, hyaluronic acid derivatives, chitosan At least one substance selected from the group consisting of chitosan derivatives, xanthan gum, carrageenan, and 20 to 98% by weight based on 100% by weight of the entecavir-containing oral film preparation.

The plasticizer also includes at least one material selected from the group consisting of acetyl triethyl citrate, polyethylene glycol (PEG), polypropylene glycol, sorbitol, glycerin, citrate ester, triacetin and triethyl citrate And 0.1 to 40% by weight based on 100% by weight of the entecavir-containing oral film preparation.

The sweetening agent may be selected from maltitol, maltitol syrup, isomalt maltitol, sorbitol, xylitol, polyol, erythritol, mannitol, sucrose, dextrose, fructose, sucralose, , At least one substance selected from the group consisting of aspartame, glycyrrhizin, stevitene, saccharin, cyclamate and sucrose fatty acid ester, wherein 0.5 to 50 wt%, based on 100 wt% of the entecavir- .

In addition, the above-mentioned flavor or taste-masking agent may be flavor, fragrance, orange, lemon, peppermint, cinnamon, menthol, peppermint oil, peppermint oil, wintergreen mint, clove, butter scotch, maple, apricot, peach flavor, cherry flavor, , At least one substance selected from the group consisting of vanillin, citrus, licorice, root beer, gardinia, raspberry, walnut, and chocolate flavor, and wherein said entecavir- 0.01 to 20% by weight.

The saliva stimulating agent may include at least one substance selected from the group consisting of citric acid, citric acid, citric acid, lactic acid, malic acid, ascorbic acid, tartaric acid, tartaric acid salt and sodium lauryl sulfate, 1 to 15% by weight based on 100% by weight of the oral film preparation.

The surfactant may also include at least one substance selected from the group consisting of poloxamer, benzalkonium chloride, benzethonium chloride, polyoxyethylene fatty acid esters, polysorbates and sorbitan fatty acid esters, and the entecavir-containing oral cavity 0.1 to 5% by weight based on 100% by weight of the film preparation.

In addition, the coloring matter may include at least one substance selected from the group consisting of titanium dioxide, silicon dioxide, zinc oxide and natural pigments, and may be included in an amount of 0.001 to 5 wt% based on 100 wt% of the entecavir-containing oral film preparation .

Also, the preservative may comprise at least one substance selected from the group consisting of methyl paraben, propyl paraben, sodium benzoate, sodium hydrogen sulfite, benzalkonium chloride and benzethonium chloride, wherein the entecavir-containing mouth film formulation comprises 100 wt% By weight based on the total weight of the composition.

The entecavir-containing film preparation according to the present invention is formed into a film preparation containing a daily dose of entecavir, which is a drug component of the hepatitis B therapeutic agent, so that it is easy to carry and take.

In addition, the entecavir-containing film preparation according to the present invention is rapidly dissolved only in the oral cavity in the oral cavity, so that it can be conveniently taken anytime and anywhere without drinking water.

Further, the entecavir-containing film preparation according to the present invention has an effect of improving the taste peculiar to a drug preparation and allowing a patient taking the hepatitis B treatment agent to easily take it.

In addition, the entecavir-containing film preparation according to the present invention has an effect of forming a groove, a protrusion or a hole on the surface thereof so that the patient can rub the film preparation between the tongue and the oral ceiling and rapidly dissolve the film preparation.

DISCLOSURE OF THE INVENTION In order to provide a composition of a film preparation containing a therapeutically effective amount of entecavir in a mixed solution containing an edible polymer and rapidly dissolving in the oral cavity and improving the feeling of discomfort as a drug, Respectively.

The entecavir-containing film preparation should have pharmacological effects, rapid film dissolution in the mouth, and acceptable feeling of use. Therefore, the entecavir-

(1) contain 0.5 mg to 1.0 mg of the daily dose of the drug in the film preparation,

(2) the film formulation in the oral cavity disintegrates between 5 and 60 seconds, and

(3) a film preparation having an organoleptic property and a thickness (preferably 30 탆 to 1000 탆) easy to take in oral cavity as an edible film preparation.

In the entecavir-containing film preparation, the film is called an edible film, a strip, an orally dissolving film, orally disintegrating film, and the like, Refers to a formulation that rapidly dissolves or disintegrates in the oral cavity. The film formulation according to the invention has the advantage that it can be taken without drinking water.

In addition, specific expressions herein have the following meanings. "Drug" means a pharmacologically active substance that provides a therapeutic effect. "Edible" is meant to be orally administrable and pharmaceutically acceptable.

The entecavir-containing film preparation of the present invention comprises 0.001 to 30% by weight, more preferably 0.1 to 12% by weight, and still more preferably 0.4 to 5% by weight of entecavir based on 100% by weight of the whole. The entecavir may be determined in terms of the area and thickness of the film preparation and the weight percentage to be mixed according to the daily dose of the drug.

In addition, the entecavir-containing film preparation may suitably contain a plasticizer, a sweetener, a flavoring agent, a taste-masking agent, a sedimentation stimulating agent, a surfactant, a coloring agent, More specifically, the entecavir-containing film preparation may be formed to include at least three components selected from plasticizers, sweeteners, flavors, taste-masking agents, sedimentation stimulants, surfactants, pigments and preservatives . For example, the entecavir-containing film preparation can be formed by including a sweetening agent, a coloring agent, and a preservative in film formation and exclusion. In addition, the entecavir-containing film preparation may be mixed with a small amount of solvent such as distilled water for smooth mixing of all components to be mixed.

The film forming agent may be at least one selected from the group consisting of pluran, starch, modified starch, pregelatinized starch, gelatin, pectin, sodium alginate, maltodextrin, polymerized rosin, hydroxypropylmethylcellulose (hypromellose), hydroxypropylcellulose , Low substituted hydroxypropyl cellulose, hydroxymethyl cellulose, methyl cellulose, sodium carboxymethyl cellulose, colicote, eudragit, polyethylene oxide, polyvinyl pyrrolidone, polyvinyl alcohol, hyaluronic acid, hyaluronic acid derivatives, Chitosan, chitosan derivatives, xanthan gum, carrageenan. These polymers may be used alone or in combination of two or more. The polymer may be included in an amount of 20 to 98% by weight, and preferably 20 to 80% by weight, based on 100% by weight of the entecavir-containing oral film preparation. As the film former, pluran may be preferably used have. When the film former is formed comprising pullulan, pullulan can be included in an amount of 30 to 65% by weight based on 100% by weight of the entecavir-containing oral film preparation. As the film forming agent, hydroxypropylmethyl cellulose and hydroxypropyl cellulose may be preferably used among the polymers. When the film former is formed to include hydroxypropylmethylcellulose and hydroxypropylcellulose, hydroxypropylmethylcellulose and hydroxypropylcellulose may be contained in an amount of 45 to 98% by weight. At this time, the hydroxypropyl methylcellulose may be contained in an amount of 19 to 91% by weight.

Plasticizers used to impart flexibility and resilience to the film formulation include acetyl triethyl citrate, polyethylene glycol (PEG), polypropylene glycol, sorbitol, glycerin, citrate ester, triacetin and triethyl citrate Lt; / RTI > These plasticizers may be used alone or in combination of two or more. Of the above plasticizers, polyethylene glycol is most preferably used because of the characteristics of the present invention. The plasticizer may be contained in an amount of 0.1 to 40% by weight based on 100% by weight of the entecavir-containing film preparation. When glycerin is used as the plasticizer, glycerin may be contained in an amount of 0.5 to 4% by weight based on 100% by weight of the entecavir-containing film preparation. In addition, when polyethylene glycol is used as the plasticizer, polyethylene glycol may be contained in an amount of 10 to 37% by weight based on 100% by weight of the entecavir-containing film preparation. On the other hand, the plasticizer may not be used when the flexibility of the film-forming agent used is moderate.

Examples of the sweetener include maltitol, maltitol syrup, isomalt maltitol, sorbitol, xylitol, polyol, erythritol, mannitol, sucrose, dextrose, fructose, sucralose, alitame, neotam, Aspartame, glycyrrhizin, stevitene, saccharin, cyclamate, sucrose fatty acid ester, and sodium saccharide. These sweeteners may be used alone or in combination of two or more. On the other hand, the sweetener may not be included depending on the required characteristics of the film preparation to be produced. The sweetener may be contained in an amount of 0.5 to 50% by weight based on 100% by weight of the entecavir-containing film preparation. When the sweetener includes asparagus and sucralose, asparagus and sucralose may be included in an amount of 17 to 20% by weight based on 100% by weight of the entecavir-containing film preparation. In addition, when the sweetener includes erythritol and sodium saccharide, erythritol and sodium saccharide may be included in an amount of 1 to 35% by weight based on 100% by weight of the entecavir-containing film preparation.

Examples of the flavor or taste masking agent include fragrance, guarana, orange flavor, lemon flavor, peppermint, cinnamon, fashion fruity, menthol, mint oil, peppermint oil, wintergreen mint, clove, butter scotch, maple, apricot, Anis, strawberry, vanillin, citrus, licorice, root beer, gardenias, raspberry, walnuts, and chocolate. The flavor or the taste-masking agent may be used alone or in combination of two or more. Meanwhile, the flavor or the taste-masking agent may not be included depending on the characteristics of the film preparation. The flavor or the taste-masking agent may be contained in an amount of 0.01 to 20% by weight based on 100% by weight of the entecavir-containing film preparation. When the peppermint oil is used as the flavoring agent, the peppermint oil may be contained in an amount of 2.0 to 10.0% by weight based on 100% by weight of the entecavir-containing film preparation. In addition, when a flavoring such as lemon flavor is used as the flavor, the flavor may be included in an amount of 0.008 to 0.015% by weight.

The saliva stimulating agent may be selected from the group consisting of citric acid, citric acid, citric acid, lactic acid, malic acid, ascorbic acid, tartaric acid, tartaric acid, sodium lauryl sulfate. The acupressure stimulant may be used alone or in combination of two or more. Meanwhile, the saliva stimulating agent may not be included depending on the characteristics of the film preparation. The salivating stimulant may be contained in an amount of 1 to 15% by weight based on 100% by weight of the entecavir-containing film preparation. When citric acid is used as the salivating stimulant, citric acid may be included in an amount of 5 to 11% by weight. When citric acid is used together with malic acid, it may be contained in an amount of 1% by weight or less based on 100% by weight of the entecavir-containing film preparation.

The surfactant may be selected from the group consisting of poloxamer, benzalkonium chloride, benzethonium chloride, polyoxyethylene fatty acid ester, polysorbate, sorbitan fatty acid ester, and the like. These surfactants may be used alone or in combination of two or more. The surfactant may be contained in an amount of 0.1 to 5% by weight based on 100% by weight of the entecavir-containing film preparation.

The coloring matter may be selected from the group consisting of titanium oxide, silicon dioxide, zinc oxide, and natural colorants. These dyes may be used alone, or two or more dyes may be used in combination. The coloring matter may be contained in an amount of 0.001 to 5% by weight based on 100% by weight of the entecavir-containing film preparation. In the case where titanium oxide is used as the coloring matter, it may be contained in an amount of 0.1 to 1.0% by weight based on 100% by weight of the entecavir-containing film preparation

The preservative may be selected from the group consisting of methyl paraben, propyl paraben, sodium benzoate, sodium hydrogen sulfite, benzalkonium chloride, benzethonium chloride. These preservatives may be used alone or in combination of two or more. The preservative may be included in an amount of 0.01 to 2% by weight based on 100% by weight of the entecavir-containing film preparation. When sodium bisulfite is used as the preservative, sodium hydrogen sulfite may be contained in an amount of 0.1 to 2% by weight based on 100% by weight of the entecavir-containing film preparation.

Though the thickness of the entecavir-containing film preparation is not particularly limited, it is preferably 30 to 1000 占 퐉. When the thickness is less than 30 mu m, the film strength is lowered and the film shape is difficult to maintain. When the thickness is more than 1000 mu m, it takes a long time to disintegrate in the oral cavity.

In addition, the form of the entecavir-containing film preparation may be formed into a film having a rectangular shape, a square shape, a circular shape, or an elliptical shape in plan view, but is not limited thereto. For example, the entecavir-containing film preparation may be formed into a square shape having rounded corners.

In addition, the entecavir-containing film preparation may have a concave-convex shape such as a hole, a groove or a projection on the surface of the film. The irregular shape increases the frictional force between the surface of the film and the upper surface of the tongue. Therefore, a patient taking the entecavir-containing film preparation rubs the surface of the film between the tongue and the ceiling of the mouth, so that the entecavir-containing film preparation can be disintegrated more quickly. In addition, the concavo-convex shape increases the contact area between the surface of the film and the needles or moisture in the oral cavity, so that the entecavir-containing film preparation is disintegrated more rapidly. The concave-convex shape may be formed in a groove or a projection shape by press-fitting the surface of the film preparation, or may be formed into a hole through a means such as a needle.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these examples are for illustrating the present invention, and the scope of the present invention is not limited to these examples.

Example

The entecavir-containing oral film preparation of the present invention is prepared as follows. In this composition, entecavir, which is a drug component, was completely dissolved in an agitator using purified water as a solvent, and after adding a plasticizer, a sweetener, a salivating stimulant, a surfactant, a dye, a preservative and the like, it was stirred again to completely dissolve or disperse. The solution was then homogenized for 60 minutes using a homogenizer. Here, the polymer was added and homogenized again using the same homogenizer. Then, a flavoring agent was added thereto and mixed using a stirrer. Subsequently, the mixed solution was degassed under a vacuum condition at 40 to 50 ° C, cooled at room temperature, and coated on PP, PET, PE and aluminum-PP films to a thickness of 30 to 1000 μm . Then, it was dried at 80 to 105 캜 to prepare a film preparation containing entecavir.

The thickness of the film preparation, the disintegration time, the degree of bitter taste, and the like were evaluated by the following method.

(Test Example)

(1) Thickness measurement

In the present invention, the thickness of the film preparation was measured using a digital thickness meter (Mitutoyo, Japan) after drying of the film, the measurement range was 0 to 10 mm, and the resolution of the measuring instrument was 0.01 mm. Thickness was measured as an average value by measuring four corners and five centers of the film (4 x 4 cm 2), and the thickness of the film preparation prepared in the following examples was measured as 30 to 1000 μm.

(2) Disintegration time measurement

In the present invention, in vitro The disintegration time on the film was measured by using a stopwatch to disintegrate the disintegration time of the film preparation (2 x 2 cm 2) into a test tube containing 10 mL of distilled water at 37 캜, which indicates the temperature in the oral cavity of a normal person. In order to measure the disintegration time in the oral cavity, the disintegration time required until the film (2 x 2 cm 2) disintegrated in the oral cavity of the subject (n = 6) was measured. Oral disintegration time was aimed at 5 to 60 seconds, which is commercially available so that the patient does not feel inconvenienced.

(3) Evaluation of bitter taste of film

In the present invention, the degree of bitter taste improvement of the film preparation is determined by adjusting the blending ratio of the flavor and the taste-masking agent in the film composition to the film (2 x 2 cm 2) 0.5 mg or 1 mg were placed in the mouth until disintegration, and the disintegrated film was spit and evaluated for the degree of bitter taste. For an accurate assessment of taste, subjects rinsed their mouths with distilled water before film samples were taken.

The evaluation of the taste was evaluated as + very bitter taste, ++ slight bitter taste, +++ very bitter taste, ++++ no taste, or a shielded taste.

(4) Method for measuring flexibility of film

The flexibility of the film was measured with a Shimadzu universal testing machine (load cell 100N). The size of the flexible measuring film was 10 × 2.5 cm 2, and the film was fixed with two clamps at a distance of 5 cm. The film was pulled at a speed of 50 mm / min and repeated three times. Physical properties of the film such as tensile strength, elastic modulus, and elongation (%) were measured.

(Examples 1 to 8)

An entecavir-containing film preparation was prepared according to the preparation method of the film formulation with the components and compositions shown in Table 1.

Results: It was found that the disintegration time of the entecavir-containing film formulation according to Table 1 varied depending on the ratio of the film former to the plasticizer. Also, it was confirmed that the content of the flavor / taste blocker had no effect on the disintegration time. The entecavir-containing film formulation according to Table 1 showed a preferred oral disintegration time of 20 to 30s.

(Examples 9 to 12)

To examine the effect of the film forming agent and the flavor / taste blocking agent on the disintegration time, the entecavir-containing film preparation was prepared as shown in Table 2 using the same method as in Examples 1 to 8 except that the same procedure was used. Respectively.

Results: In the entecavir-containing film formulations according to Table 2, there was no difference in the disintegration time according to the type and content of the flavor / flavor blocking agent, and the disintegration time was changed according to the content of the film former. The entecavir-containing film formulation according to Table 2 showed a preferred oral disintegration time of 25 to 30 s.

(Examples 13 to 17)

To examine the effect of the film former on the disintegration time more specifically, the entecavir-containing film preparation was prepared as shown in Table 3, using the same method as in Examples 9 to 12 except that the composition was different. As examples of the film forming agents in Examples 13 to 17, pluran, starch, carrageenan and crystalline cellulose were used in combination.

Results: When the starch, carrageenan, crystalline cellulose and the like were used in addition to pullulan as a film-forming agent, the entecavir-containing film preparation according to Table 3 was prepared in such a manner that, based on the blending ratio of pullulan and starch, Disintegration time was found to vary. The entecavir-containing film formulation according to Table 3 showed a preferred oral disintegration time of 25 to 30 s.

(Examples 18 to 23)

Using the same method as in Examples 1 to 8 but differing in content of entecavir, the entecavir-containing film preparation was prepared as shown in Table 4.

Results: Entecavir-containing film preparations according to Table 4 showed a preferred oral disintegration time of 5 to 15 s.

(Examples 24 to 26)

The entecavir-containing film preparation was prepared as shown in Table 5 using the same method, except that the content of entecavir was different from that of Examples 1 to 8.

Results: The entecavir-containing film formulation according to Table 5 showed a preferred oral disintegration time of 11-12 s.

(Examples 27 to 29)

The entecavir-containing film preparations were prepared as shown in Table 6 using the same method as in Examples 1 to 8 except that the kinds and contents of the components were different.

Results: Entecavir-containing film formulations according to Table 6 did not stick to the oral ceiling in the mouth, leaving no stickiness in the mouth. This is because the cellulose component used as a film-forming agent disintegrates in the oral cavity, leaving no stickiness in the mouth. In addition, the film formulations of Table 6 showed a disintegration time of 8 to 12 seconds. The low substituted hydroxypropyl cellulose used as a film former improves the disintegration rate. On the other hand, the hydroxypropylmethylcellulose used as the film former maintains the rigidity of the film, and the hydroxypropylcellulose increases the flexibility of the film.

(Examples 30 to 32)

The entecavir-containing film preparations were prepared as shown in Table 7 using the same method as in Examples 1 to 8 except that the kinds and contents of the components were different.

Results: The entecavir-containing film formulation according to Table 7 showed a disintegration time of 5 to 8 minutes and a disintegration time of 1 minute or less in the oral cavity. In addition, the entecavir-containing film preparation according to Table 7 did not remain sticky to the mouth without sticking to the oral ceiling in the mouth.

(Examples 33 to 35)

The entecavir-containing film preparations were prepared as shown in Table 8 using the same method as in Examples 1 to 8 except that the kinds and contents of the components were different.

Results: The entecavir-containing film formulation according to Table 8 showed a disintegration time of 3 to 6 minutes and a disintegration time of 1 minute or less in the oral cavity. In addition, the entecavir-containing film preparation according to Table 8 did not stick to the oral ceiling in the mouth, and left no stickiness in the mouth. The maltitol syrup and erythritol contained in the entecavir-containing film preparation according to Table 8 are included as a cost-reducing agent and shorten the disintegration time together with the sweetening function. In other words, maltitol syrup increases the flexibility and disintegration speed of the film along with the cost function, and erythritol increases the disintegration rate with sweetening function.

(Examples 36 to 40)

The entecavir-containing film preparations were prepared as shown in Table 9 using the same method as in Examples 1 to 8 except that the kinds and contents of the components were different.

Results: The entecavir-containing film formulation according to Table 9 showed a disintegration time of 3 to 8 minutes and a disintegration time of 1 minute or less in the oral cavity. In addition, the entecavir-containing film preparation according to Table 9 did not stick to the oral ceiling in the mouth, and left no stickiness in the mouth. On the other hand, the entecavir-containing film preparation according to Table 9 did not use low-substituted hydroxypropyl cellulose having a relatively small effect on the flexibility and disintegration of the film.

(Examples 41 to 48)

The entecavir-containing film preparation was prepared as shown in Table 10 using the same method as in Examples 1 to 8 except that the kinds and contents of the components were different.

Results: The entecavir-containing film formulation according to Table 10 showed a disintegration time of 30 seconds to 2 minutes in the evaluation of the disintegration of the test tube, and a disintegration period of 5 to 30 seconds in the oral cavity. In addition, the entecavir-containing film formulation according to Table 10 was sticky to the oral ceiling and left a sticky texture, which did not cause discomfort or residual perspiration in the mouth. In addition, the entecavir-containing film preparations according to Table 10 exhibited good results that maintained adequate elasticity and did not break well.

From the results of Tables 1 to 10, it can be seen that the entecavir-containing film preparation prepared according to the present invention contains 0.001-30 wt%, more preferably 0.1-12 wt% entecavir, , 0.4 to 5% by weight, and is appropriately blended with polymers such as pluran, starch and cellulose to disintegrate in the oral cavity in the range of 5 to 30 seconds in oral cavity water, and other flavor / Or the like is used to form an entecavir-containing film preparation composition having improved specificity or odor.

Claims (13)

An oral disintegrating film preparation containing entecavir for treating hepatitis B containing entecavir as an active ingredient. The method according to claim 1,
Wherein the entecavir is contained in an amount of 0.001 to 30% by weight based on 100% by weight of the entecavir-containing oral disintegrating film preparation. The method according to claim 1,
Wherein the entecavir is contained in an amount of 0.1 to 12% by weight based on 100% by weight of the entecavir-containing oral disintegrating film preparation. The method according to claim 1,
Wherein the entecavir is contained in an amount of 0.4 to 5.0% by weight based on 100% by weight of the entecavir-containing oral disintegrating film preparation. The method according to claim 1,
Wherein the entecavir-containing oral disintegrating film preparation comprises at least three components selected from a plasticizer, a sweetener, a flavoring agent, a taste-masking agent, a sedimentation-stimulating agent, a surfactant, a pigment and a preservative together with a film- Disintegration-type film preparation containing entecavir. 6. The method of claim 5,
Wherein the film forming agent comprises at least one material selected from the group consisting of pullulan, starch, hydroxypropylmethyl cellulose (hydroxypropyl cellulose), hydroxypropyl cellulose, low substituted hydroxypropyl cellulose, crystalline cellulose and carrageenan , And 20 to 80% by weight based on 100% by weight of the entecavir-containing mouth rinse-type film preparation. 6. The method of claim 5,
Wherein the plasticizer comprises at least one substance selected from the group consisting of polyethylene glycol (PEG) and glycerin, and 0.1 to 30% by weight based on 100% by weight of the entecavir-containing oral disintegrating film preparation Disintegration-type film preparation containing entecavir. 6. The method of claim 5,
Wherein the sweetener comprises at least one substance selected from the group consisting of maltitol syrup, xylitol, erythritol, sucralose, aspartame, stevitene, sodium saccharide and sucrose fatty acid ester, and the entecavir- By weight based on 100% by weight of the film preparation. ≪ RTI ID = 0.0 > 20. < / RTI > 6. The method of claim 5,
The flavor or taste blocking agent may be selected from the group consisting of flavorings, fragrance, orange, lemon, peppermint, cinnamon, menthol, mint oil, peppermint oil, winter mint, clove, butter scotch, maple, apricot, peach flavor, , At least one substance selected from the group consisting of citrus, licorice, root beer, gardenias, raspberry, walnuts, and chocolates, and wherein at least one substance selected from the group consisting of 100 wt.% Of the entecavir- 0.01 to 10% by weight, based on the total weight of the composition. 6. The method of claim 5,
Wherein the saliva stimulating stimulant comprises at least one substance selected from the group consisting of citric acid, citric acid and malic acid, and is contained in an amount of 1 to 10% by weight based on 100% by weight of the entecavir-containing oral disintegrating film preparation Disintegration-type film preparation containing entecavir. 6. The method of claim 5,
Wherein the surfactant comprises at least one material selected from the group consisting of poloxamer, benzalkonium chloride, benzethonium chloride, polyoxyethylene fatty acid esters, polysorbates and sorbitan fatty acid esters, and the entecavir- And 0.1 to 5% by weight, based on 100% by weight of the film preparation, of an enteric-coated, oral disintegrating film. 6. The method of claim 5,
Wherein the coloring matter comprises at least one substance selected from the group consisting of titanium dioxide, silicon dioxide, zinc oxide and natural coloring matter and is contained in an amount of 0.001 to 5% by weight based on 100% by weight of the entecavir-containing oral disintegration film preparation Wherein the entecavir-containing mouth rinse-type film preparation comprises: 6. The method of claim 5,
Wherein the preservative comprises at least one material selected from the group consisting of methyl paraben, propyl paraben, sodium benzoate, sodium hydrogen sulfite, benzalkonium chloride and benzethonium chloride, and wherein the entecavir-containing oral disintegrative film preparation comprises 100 wt% By weight based on 100% by weight of the total amount of the entecavir-containing oral debonding film.