KR20150126613A - Coating compositon, coated preparation and method for producing same - Google Patents

Abstract

(A) an alginate and (B) a plasticizer, it is possible to dissolve the coating composition in the field without melting the coating composition to reach the coating material such as the coated active ingredient, A coating composition excellent in coatability due to its ability to be coated, and a coating formulation coated with the coating composition.

Description

TECHNICAL FIELD [0001] The present invention relates to a coating composition, a coating composition,

TECHNICAL FIELD [0001] The present invention relates to a coating composition, a coating agent, and a method for producing the same, which are used for coating foods, medicines, and the like.

There is an active ingredient which brings out the high functionality by preventing the decomposition in the stomach and maintaining the structure and reaching the intestine like the functional ingredient of the protein such as lactic acid bacteria and enzyme, Soluble (enteric) formulations which dissolve the active ingredients and reach the intestines.

Examples of the protective film for reaching the effective ingredient to the intestine include a component dissolving in the pH condition (neutral to alkaline) of the small intestine without dissolving in the stomach pH condition (acidic), for example, a methacrylic acid based high molecular compound, And so on.

However, the methacrylic polymer is limited to pharmaceutical use and can not be used for food. On the other hand, shekel and jane are also used for food, but a method of spraying with an organic solvent is common. It is desired to use a water-soluble membrane agent capable of coating with water in consideration of the environment even for foods.

Patent Document 1: JP-A-2002-193792

Disclosed is a coating composition which can dissolve in a field without being melted from above, can reach a coating material such as a coated active ingredient, can be uniformly coated without chipping or peeling, And to provide a coated coating preparation and a method for producing the same.

The inventors of the present invention have found that a coating composition comprising an alginate and a plasticizer dissolves in the intestines without melting from above and can reach the coating material such as an active ingredient and is excellent in coating properties, It has reached the end.

Accordingly, the present invention provides the following.

[One]. (A) an alginate and (B) a plasticizer.

[2]. Wherein the component (A) is an alginate selected from sodium alginate, potassium alginate and ammonium alginate.

[3]. The coating composition according to [1] or [2], wherein the component (A) is an alginate (A-1) having a viscosity at 20 캜 of an aqueous solution of 1 mass%

[4]. Wherein the component (A) is at least one selected from the group consisting of alginic acid salt (A-1) having a viscosity at 20 占 폚 of 1% by mass aqueous solution exceeding 50 MPa 占 퐏 and alginic acid having a viscosity of 20% The coating composition according to [1] or [2], which is a salt (A-2).

[5]. [1] The pharmaceutical composition according to [1], further comprising (C) a component selected from the group consisting of gelatin, pectin, cardanol, fluoran, gum arabic, xanthan gum, gellan gum, hydroxypropylmethyl cellulose, carboxymethyl cellulose sodium and hydroxypropyl cellulose. To (4).

[6]. The coating composition according to any one of [1] to [5], further comprising (D) fine particles.

[7]. The coating composition according to any one of [1] to [6], wherein the component (B) is glycerin and / or a sucrose fatty acid ester.

[8]. The coating composition according to any one of (1) to (7), wherein the weight ratio of (A): (C) is from 1:10 to 20: 1.

[9]. A coating formulation having a coating film formed from the coating composition according to any one of [1] to [8].

[10]. An enteric coating preparation based on [9] wherein the coating film is soluble.

[11]. A step of spraying a coating solution containing water and the coating composition described in any one of [1] to [8] and drying to form a coating film on the surface of the coating material, ≪ / RTI >

According to the coating composition of the present invention, it is possible to provide a coating composition which can dissolve in the intestines without melting from above, reach the coated active ingredient, and is excellent in coating property, a coating preparation coated with the coating composition, have.

1 is a graph showing the results of a test example.

Hereinafter, the present invention will be described in detail.

(I) coating composition

The coating composition of the present invention contains (A) an alginate and (B) a plasticizer.

(A) Alginate

The alginate is preferably a monovalent alginate such as a sodium salt, a potassium salt, or an ammonium salt, or an alginic acid water-soluble salt. As the alginate, the viscosity at 20 캜 of the aqueous solution of 1 mass% of (A-1) exceeds 50 · m s, the viscosity of the aqueous solution of 1 mass% of (A-2) , And they may be used alone or in combination of two or more.

It is preferable that the viscosity at 20 캜 of the 1 mass% aqueous solution of (A-1) exceeds 50 · m s and is preferably 600 · e s or higher, more preferably exceeds 50 · e 하고 More preferably 400 MPa s or less.

The alginate having a viscosity at 20 캜 of not more than 50 MPa s of the 1 mass% aqueous solution of (A-2) is preferably 5 to 50 MPa s, more preferably 10 to 50 MPa.. As the alginate (A-2), sodium alginate is preferable.

The blending amount of the component (A) is preferably from 5 to 85 mass% (solid content: hereinafter referred to as a solid content, in proportion to the total amount of the components excluding the solvent, the same as the ratio in the coating film) to the coating composition. , More preferably in the range of 10 to 70 mass% (solid content), and still more preferably in the range of 10 to 60 mass% (solid content).

When the (A-1) alginate is blended, the blending amount is preferably 5 to 85 mass% (solids content), more preferably 10 to 60 mass% (solid content), and more preferably 20 to 50 mass% Solid content) is more preferable. By setting the amount to be in the above range, good solubility can be obtained. When the amount is less than the above range, adhesion and peeling at the time of coating can be prevented, and good coating performance can be obtained.

When the (A-2) alginate is blended, the blending amount is preferably 85 mass% (solid content) or less, more preferably 5 to 50 mass% (solid content), and more preferably 10 to 40 mass% ) Is more preferable. When the amount is in the above range, the solubility is improved and the coating property is improved.

In the present invention, alginate (A-1) is preferably used as the alginate (A). By using the alginate having a length equal to or longer than the predetermined length, the coating property is good. A high acid resistance can be imparted to the formed coating film. In addition, by using the alginate (A-1) and the alginate (A-2) in combination, the coating performance can be further improved while maintaining the suppleness.

Use of two kinds of alginates having different viscosities, such as the alginate (A-1) and the alginate (A-2), is not limited to adjusting the viscosity of the coating solution, Two kinds of alginates were chosen. The mass ratio is preferably 1: 5 to 10: 1 (0.2 to 10), more preferably 1: 3 to 5: 1 (A-1) 1 (0.33 to 5), and more preferably 1: 1.8 to 3: 1 (0.56 to 3). When the amount is higher than the lower limit (lower limit), the coating performance in acidification (acidification) becomes higher, so that the non-dissolution property becomes good, and when it is not more than the upper limit, the coating property becomes better.

In the present invention, the viscosity of alginate is measured by using a rotary clay system (BM type). Viscosity of less than 200 MPa · s indicates the viscosity of the rotor No. 3. 1, and a viscosity of 200 MPa · s or more and less than 1,000 MPa · s is used as the rotor No. 1. 2, and the 1 mass% aqueous solution is measured under the conditions of 20 占 폚 and 30 rpm, and the value after 60 seconds is used as a measurement value.

The viscosity of the alginate salt is approximately proportional to the molecular weight of the alginate salt. For example, the weight average molecular weight (Mw) of (A-1) is preferably 800,000 or more, more preferably 80,000 to less than 3,000,000, and even more preferably 80 to 1,000,000 or less. (A-2) has a weight-average molecular weight (Mw) of 200,000 or more and less than 800,000, and preferably 300,000 or more and less than 800,000. The method of measuring the weight average molecular weight (Mw) of the alginate of the present invention by gel chromatography is shown below.

(1) Preparation of samples

(Mobile phase) (0.1 M (mol / l) NaNO ₃ aqueous solution) so that the alginate concentration is 0.1 mass%, and this is taken as a sample.

A calibration curve is prepared using standard products of various molecular weights (plulan: Mw = 166,000, Mw = 380,000, Mw = 100,000, Mw = 1.22 million, dissolved in the mobile phase at a concentration of 0.1 mass%).

(2) GPC measurement conditions

Column: Shodex OHpak SB-806M HQ (8 mm I. D x 300 mm L, 13 m)

Mobile phase: 0.1 M (mol / l) NaNO ₃ aqueous solution

Flow rate: 0.5 ml / min

Temperature: 40 ° C

Injection amount: 200 μl (0.1% in mobile phase)

Detector: Differential Refractive Index (RI) detector

(3) Analysis method

The calibration curve equation is obtained from the calibration curve sample, and the weight average molecular weight (Mw) in terms of pullulan is obtained from the GPC analysis result of the sample.

(B) a plasticizer

Examples of the plasticizer include surfactants such as sucrose fatty acid esters, glycerin fatty acid esters, monoglycerin fatty acid esters and polyoxyethylene sorbitan fatty acid esters, polyhydric alcohols such as glycerin, propylene glycol and polyethylene glycol, sugars such as glucose, fructose glucose, (Sugar), sugar alcohols such as sorbitol, maltitol, mannitol, erythritol and xylitol, dodecanol, tridecanol, tetradecanol, pentadecanol, hexadecanol, heptadecanol, octadecanol, hexadecyl alcohol , Fatty alcohols such as isostearyl alcohol, 2-octyldodecanol (preferably having 6 to 22 carbon atoms) and medium chain (medium chain) fatty acid esters (preferably 6 to 12 carbon atoms). These may be used singly or in combination of two or more. Among them, glycerin is preferable from the viewpoint of the plasticizing effect of the coating film, and surfactant is preferable from the viewpoint of the endurance, and glycerin and / or sucrose fatty acid ester is more preferable.

The blending amount of the component (B) is preferably from 0.1 to 70 mass% (solid content), more preferably from 2 to 50 mass% (solid content), based on the coating composition. By setting the amount to be in the above range, the peeling of the film at the time of coating is further suppressed. When the amount is less than the above range, tackiness during coating is suppressed, coating treatment becomes easier and satisfactory solubility can be obtained.

The mass ratio represented by (B) / (A) is preferably in the range of 0.05 to 3.0, more preferably 0.1 to 2.0, further preferably 0.15 to 1.5, and particularly preferably 0.15 to 1.1. When the content is in the above-mentioned range, the coating performance in acidification becomes higher, and when it is less than the upper limit, the coating property becomes better.

A coating film forming component other than (A) may be blended into the coating composition of the present invention. (C) film-forming components include gelatin, pectin, cardanol, fluoran, gum arabic, xanthan gum, gellan gum, hydroxypropyl methylcellulose, carboxymethylcellulose sodium, hydroxypropylcellulose, agar, chitosan, tamarind Seed rubber, locust bean gum, polyvinyl alcohol, ethyl cellulose aqueous dispersion and the like. These may be used singly or in combination of two or more. Among these, the components selected from gelatin, pectin, cardanol, fluoran, gum arabic, xanthan gum, gellan gum, hydroxypropylmethyl cellulose, carboxymethyl cellulose sodium and hydroxypropyl cellulose have a coating property and (A) Is preferable in terms of combination with the component.

In this case, the content by mass ratio expressed by (A) :( C) ((A) / (C)) is preferably from 1:10 to 20: More preferably from 1: 1 to 10: 1 (1 to 10). By setting the content within this range, it is possible to obtain tablets excellent in intestinal performance, in which the coating performance under acidic conditions is maintained, while maintaining the beauty of coating and appearance,

The amount of the component (C) is preferably from 1 to 90 mass% (solids content), more preferably from 5 to 80 mass% (solid content), and still more preferably from 10 to 80 mass% (solid content) based on the coating composition. When the amount is in the above range, the effect of compounding the component (C) can be further obtained, and if it exceeds the above range, there is a fear of affecting the solubility.

(D) fine particles may be added to the coating composition. By blending the fine particles, it is possible to prevent peeling of the coating film due to adhesion of the tablets in the coating process. Examples of the component (D) include talc, calcium stearate, silicon dioxide, and titanium oxide. These can be used alone or in combination of two or more. The particle size of the fine particles is 0.01 to 50 mu m, preferably 0.1 to 20 mu m. The particle size is measured by a laser diffraction particle distribution measuring apparatus (dry measurement).

The amount of the component (D) is preferably from 1 to 80 mass% (solids content), more preferably from 3 to 60 mass% (solid content), and still more preferably from 5 to 40 mass% (solid content) based on the coating composition. When the amount is in the above range, the effect of compounding the component (D) can be further obtained. If the amount exceeds the above range, the film-forming property may be affected.

Further, it is preferable that the coating composition does not contain a divalent metal ion such as copper ion, barium ion or calcium ion. This is because the alginate is crosslinked (cross-linked) to gel, resulting in poor coating properties. That is, when the monovalent alginate is crosslinked by reacting with a divalent cation, the dried film is insoluble in water but becomes too viscous due to gelation, so that the spreadability of the fine solution on the spraying and purification becomes difficult. As a result, it becomes difficult to form a uniform film and the appearance is deteriorated, and in addition, deviation may occur in the elution property. The acceptable range of the divalent metal ion is preferably 0.25 mol or less, more preferably 0.1 mol or less, based on 1 mol of the monomer of the alginate.

In addition to the above components (A) to (D), the coating composition of the present invention may contain one or more kinds of components commonly used in the coating composition. Examples of such optional components include a defoaming agent and a coloring agent.

Examples of the antifoaming agent include glycerin fatty acid ester, dimethylpolysiloxane, dimethylpolysiloxane-silicon dioxide mixture, water-containing silicon dioxide, silicon dioxide, etc. These solvents may be used singly or in combination of two or more. have.

Examples of the coloring agent include, but are not limited to, Asepen tannin extract, Ulgum extract, Yellow ferric oxide, Orange essence, Brown iron oxide, Carbon black, Caramel, Carmin, Carotene liquid, Yellow gold No. 4, aluminum yellow No. 4 aluminum lake, edible yellow No. 5, edible red No. 2, edible red No. 3, food yellow No. 4, food yellow No. 4 aluminum lake, edible yellow No. 5, edible red No. 2, edible red No. 3, (Riboflavin), Riboflavin, Green tea horse, Riboflavin sodium phosphate and the like, and the like can be used in the present invention. .

The coating composition of the present invention may contain an organic solvent such as water or ethanol within a range not to impair the effect of the present invention. The amount of the solvent to be blended in the coating composition is appropriately selected in the range of 1 to 98 mass%, preferably 50 to 98 mass%, and more preferably 70 to 96 mass%, based on the entire coating composition.

(II) coating formulation

By using the above-mentioned coating composition, a coating film formed of a coating composition can be formed on the coating material to form a coating formulation.

The coating film formed from the coating composition of the present invention contains the above component (A), and an aqueous alginic acid solution is directly dried to form a water-soluble film as described later. This water-soluble membrane has a characteristic that a monovalent cation is replaced with a hydrogen ion and changes to alginic acid to form an insoluble film under acidic conditions, and dissolves in a neutral to alkaline state.

The coating composition of the present invention and the coating film formed of the coating composition can be soluble in the enteric field without melting on the enteric, that is, from above, and the coated material can reach the intestine. &Quot; An enteric coating preparation having a coating film in an enteric form can be obtained.

In the present invention, " enteric property " means a substance that reaches functional components up to the intestines. The test was conducted in accordance with the method of the dissolution test method of the Japanese Pharmacopoeia and the dissolution test solution (pH 6.8) corresponding to the intestinal juice was measured at a dissolution test solution (pH 1.2) corresponding to the gastric juice at a dissolution rate of less than 50% (suitably 30% Refers to a dissolution rate of 70% or more in 2 hours.

The form and form of the coated material are not particularly limited and are not particularly limited, such as tablets, powders, fine granules and granules. The tablet may be a single layer or two or more layers. Of these, tablets are preferred from the viewpoint of exerting more endurance. The size of the tablet is not particularly limited, and the diameter of the tablet is preferably from 5 to 14 mm, more preferably from 7 to 12 mm, from the viewpoints of easy handling and drowning of the tablet. In addition, 150 to 700 mg of purified water per tablet is suitable.

The thickness of the coating film is not particularly limited, but is preferably 5 m to 1 mm, more preferably 10 to 500 m. In the case of tablets, the coating film is preferably 0.5 to 20% by mass, more preferably 1 to 15% by mass, based on the coating formulation. In the case of granules, powders and powders, the content is preferably 10 to 60 mass%, more preferably 15 to 50 mass%. The content (solid content) of each component in the coating film is the same as that of the above-mentioned coating composition.

The coating material is not particularly limited, and examples thereof include active ingredients such as foods and medicines. Examples thereof include proteins such as lactic acid bacteria, cysteine, iron, antibodies and lactoferrin, peptides, ATP-2Na, etc. These can be used singly or in combination of two or more. Among them, it is suitable for a high molecular weight component such as protein and a water insoluble component.

(III) Method for producing a coating formulation

The coating composition can be obtained by mixing the above-mentioned essential components, and the coating agent forms a coating film on the surface of the coating material by spraying the coating composition with the coating composition as it is, Lt; / RTI > Since the coating composition of the present invention is aqueous, coating using water is possible, and a water-soluble film is formed.

The coating solution includes a coating composition and water, and the water content of the coating solution is preferably 50 to 98 mass%, more preferably 70 to 96 mass%. In addition, an organic solvent such as ethanol may be blended to the extent that the effect of the present invention is not impaired.

The coating apparatus is not particularly limited, and a pan coater, a fluidized bed coater, an electric coating, or the like can be used.

The coating method is not particularly limited, and for example, a method in which the coating solution is film-formed on the surface of the coating by spraying the coating solution and drying by heating. The coating solution can be suitably heated, the temperature is preferably 30 to 80 占 폚, and the drying temperature is preferably 40 to 80 占 폚. The coating solution is preferably added at a rate of 1 to 5 g / min with respect to a dry air volume of 1 m < 3 > / min. It is also possible to adopt a dip coating method in which a coating solution is immersed in a coating solution and dried. The drying is preferably carried out until the water content in the coating formulation becomes 0.1 to 20% by mass.

Example

EXAMPLES Hereinafter, the present invention will be described in detail by way of examples and comparative examples, but the present invention is not limited to the following examples. In the following examples, unless otherwise specified, "%" of the composition represents mass%, and the ratio represents the mass ratio.

[Examples 1-78, Comparative Examples 1-4]

The following coating compositions were prepared, and coating solutions having the compositions shown in the following Tables 1 to 22 were prepared and coated (predetermined tablets) in the following manner to prepare coated tablets.

[Predetermined (unlocked)]

The following raw materials were mixed and subjected to tableting using a tablet machine so as to obtain tablets (300 mg,? 9.0 mm, thickness: 5 mm).

≪ Prescribed (raw tablet) composition >

Lactoferrin: 1,156 g

End of Hiharts extract: 500g

Lactose: 492.5g

Crystalline cellulose: 731.5 g

Carboxymethylcellulose sodium: 60 g

Sucrose fatty acid ester: 30 g

Fine silicon dioxide: 30 g

[Preparation of Coating Solution]

In each of the coating solution compositions shown in Tables 1 to 22, the components (A) and (C) were uniformly dissolved in heated water, the dissolved solution was mixed, and the other components were added and mixed and stirred again. In the table, the right column (right column) represents the solid content (%).

[coating]

100 g of a coating solution (60 DEG C) was sprayed at an average of 2 g / min on 200 g of a cleaning agent using a coater (PURRAX PURECKA PRC-05) and coating was carried out at a product temperature of about 50 deg. After spraying, the coating was dried at about 45 DEG C for 2 minutes to obtain a coating agent (tablets). The thickness of the coating film was in the range of 10 to 200 mu m.

[Acidic pH non-availability test]

The dissolution test was carried out in accordance with the National Institute of Advanced Industrial Science and Technology (National Institute of Advanced Industrial Science and Technology) using one liquid (one station, one solution) (pH 1.2).

◎: Elution at 2 hours 10% or less

○: elution from 10% to 30% at 2 hours

≪ DELTA: >: elution property at 2 hours exceeding 30% and less than 50%

X: elution at 50% or less at 2 hours

[Neutral to alkaline pH elution test]

The dissolution test was carried out using two liquids (pH 6.8) in one country in accordance with the General National Test Methods (paddle method).

○: Elution at 70% or more in 2 hours

DELTA: elution property at 2 hours 30% or more and less than 70%

X: Less than 30% elution at 2 hours

In the above [acidic pH elution test], the case of "?", "?" Or "?" And the case of "?" In the above [neutral to alkaline pH elution test]

[Coating property]

The coating properties were evaluated on the basis of the following evaluation criteria.

⊚: Coating is uniformly performed, chipping and peeling are not observed, and the surface of the coating is glossy.

○: Coating is uniformly performed, chipping and peeling are hardly observed, but there is roughness on the surface of the coating slightly.

?: Particles of the coating are seen in some tablets.

X: Most of the tablets show chipping or exfoliation of the coating.

[Table 1]

[Table 2]

[Table 3]

[Table 4]

[Table 5]

[Table 6]

[Table 7]

[Table 8]

[Table 9]

[Table 10]

[Table 11]

[Table 12]

[Table 13]

[Table 14]

[Table 15]

[Table 16]

[Table 17]

[Table 18]

[Table 19]

[Table 20]

[Table 21]

[Table 22]

The number of moles of the calcium ion with respect to 1 mole of the monomers of the alginate salts of Examples 75 to 78 is as follows.

Example 75: 0.014 mol

Example 76: 0.027 mol

Example 77: 0.041 mol

Example 78: 0.054 mol

≪ Test Example 1 >

Six tablets of the coated tablets prepared in Examples 38 and 53 and Comparative Examples 1 and 2 were placed in a solution of 100 ml of pH 1.2 (1 liquid of one country + pepsin dissolution test liquid) at 37 占 폚 and stirred for 2 hours with a shaker. Thereafter, treatment was carried out at 100 ° C for 20 minutes to inactivate pepsin. After cooling to 37 DEG C, 110 mL of a pH 8.5 aqueous sodium hydrogen carbonate solution at 37 DEG C was added, the pH was adjusted to about 6.0, and the mixture was further stirred for 2 hours with shaking. This solution was filtered with a 0.45 mu m filter to obtain an evaluation sample.

Human precursor adipocytes were seeded on a 24-well plate at 3.0 × 10 ⁵ CELL / cm 2 in a visceral fat cell differentiation medium (Primary Cell Company Limited, Tokyo, Japan) CO ₂ environment and it was cultured in 37 ℃. Thereafter, 1 ml of the diluted test sample is diluted 10 times in the medium, and the resultant is cultured for 24 hours. Thereafter, the concentration of glycerol in the supernatant was measured. As compared with the control and Comparative Example 1, in the Examples, the concentration of glycerol produced by accelerating the decomposition of fat by lactoferrin was elevated, and it was confirmed that the coated tablet of the Example was enteric. The results are shown in Fig.

The raw materials used in preparing examples and comparative examples are shown below. In the table, the respective component amounts are shown.

[Table 23]

[Table 24]

Claims (11)

(A) an alginate and (B) a plasticizer. The method according to claim 1,
Wherein the component (A) is an alginate selected from sodium alginate, potassium alginate and ammonium alginate. 3. The method according to claim 1 or 2,
Wherein the component (A) is an alginate (A-1) having a viscosity of 1 mass% aqueous solution at 20 캜 of more than 50 MPa · s. 3. The method according to claim 1 or 2,
Wherein the component (A) is at least one selected from the group consisting of alginic acid salt (A-1) having a viscosity at 20 占 폚 of 1% by mass aqueous solution exceeding 50 MPa 占 퐏 and alginic acid having a viscosity of 20% (A-2). ≪ / RTI > 5. The method according to any one of claims 1 to 4,
Also, it is characterized in that it contains (C) a component selected from gelatin, pectin, cadulan, fluoran, gum arabic, xanthan gum, gellan gum, hydroxypropyl methylcellulose, sodium carboxymethylcellulose and hydroxypropylcellulose ≪ / RTI > 6. The method according to any one of claims 1 to 5,
And (D) fine particles. 7. The method according to any one of claims 1 to 6,
Wherein the component (B) is a glycerin and / or a sucrose fatty acid ester. 8. The method according to any one of claims 1 to 7,
(A) :( C) is in the range of 1:10 to 20: 1. A coating formulation having a coating film formed from the coating composition according to any one of claims 1 to 8. 10. The method of claim 9,
Wherein the coating film is enteric. And a step of spraying a coating solution containing the coating composition described in any one of claims 1 to 8 and water onto the coating material and drying to form a coating film on the surface of the coating material ≪ / RTI >

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