Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2833—Organic macromolecular compounds
  • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
  • A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
  • A23P20/10—Coating with edible coatings, e.g. with oils or fats
  • A23P20/105—Coating with compositions containing vegetable or microbial fermentation gums, e.g. cellulose or derivatives; Coating with edible polymers, e.g. polyvinyalcohol
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/02—Inorganic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2813—Inorganic compounds

Definitions

• the present invention relates to a coating composition, a coating film, a coating preparation and a method for producing the same, which are used for coating of food, medicine and the like.
• a component that does not dissolve in the pH condition (acidity) in the stomach but dissolves in the pH condition of the small intestine (neutral to alkaline) is used.
• examples of such components include methacrylic acid-based polymer compounds, shellac, zein, alginate and the like, but methacrylic acid-based polymer compounds are limited to pharmaceutical applications, and shellac and zein are organic solvents.
• enteric coated membrane preparations using alginate may have reduced gastric juice resistance performance due to deterioration of the coating membrane, which is considered to be caused by hydrolysis of alginate, when stored in a high temperature and humidity environment. there were. Therefore, there is a demand for a coating technique that can suppress the decrease in gastric juice resistance even when stored in a high temperature and high humidity environment.
• the present invention can be obtained using a coating composition that provides a coating film that is not chipped, peeled off, uniformly coated, is excellent in coating properties, and is also excellent in durability under high temperature and high humidity environments. It is an object of the present invention to provide a coating film, a coating preparation coated with the coating composition, and a method for producing the same.
• a coating composition containing an alginate and a divalent cation in a predetermined ratio can be uniformly coated without chipping and peeling, and has excellent coating properties.
• the preparation coated with the composition has resistance to gastric juice even when stored under high temperature and high humidity environment. It was found that the decrease was small and the storage stability was excellent.
• a coating film containing an alginate and a divalent cation in a predetermined ratio is excellent in durability under high temperature and high humidity environment, and a coating preparation covered with the coating film is under high temperature and high humidity environment. Even when stored, the deterioration of gastric juice resistance is small, and it has been found that the storage stability is excellent, and the present invention has been achieved.
• the present invention provides the following.
• the content mass ratio of the (B) component to the (A) component represented by (B) / (A) ⁇ 100 containing (A) alginate and (B) divalent cation is 0.015 Coating composition characterized by being -0.25.
• the coating composition of [1] wherein the component (A) is an alginate having a viscosity of 600 mPa ⁇ s or less at 20 ° C. of a 1% by mass aqueous solution.
• [4] The coating composition according to [3], wherein the mass ratio of the component (B) to the component (C) represented by (B) / (C) ⁇ 100 is 0.02 to 5.
• a step of forming a coating film on the surface of the article to be coated by spraying a coating solution containing the coating composition of any of [1] to [5] and water onto the article to be coated and drying it.
• a method of producing a coating preparation including: [8] A coating film formed on the surface of a material to be coated, comprising (A) an alginate and (B) divalent cations, and represented by (B) / (A) ⁇ 100 (A) ) A coating film characterized in that the content mass ratio of the component (B) to the component (B) is 0.015 to 0.25. [9] The coating film of [8], further comprising (C) a plasticizer. [10] The coating film of [9], wherein the content mass ratio of the component (B) to the component (C) represented by (B) / (C) ⁇ 100 is 0.02 to 5. [11] The coating film of any one of [8] to [10], which further comprises (D) a film-forming component.
• a coating composition which not only has excellent coating properties but also provides a coating film excellent in durability under high temperature and humidity environments, a coating film obtained using this coating composition, and this coating composition It is possible to provide a coated preparation having excellent storage stability and a method for producing the same. Moreover, the coating film which is excellent in the durability in the environment of high temperature and high humidity, and its manufacturing method can be provided.
• the coating composition of the present invention contains (A) alginate and (B) divalent cations.
• Alginate As the alginate, monovalent alginates such as alkali metal salts and ammonium salts, and water soluble alginates are preferable, alkali metal salts are more preferable, sodium salts and potassium salts are more preferable, sodium is more preferable Salt is more preferred.
• alginate one having an appropriate viscosity can be used singly or in combination of two or more, and the viscosity as a whole is 600 mPa ⁇ s as the viscosity at 20 ° C. of a 1% by mass aqueous solution. The following are preferable, and 25 mPa ⁇ s or more and 400 mPa ⁇ s or less are more preferable.
• alginate (A-1) As an alginate having a viscosity of 50 mPa ⁇ s or more at 20 ° C. of a 1% by mass aqueous solution, one having 50 mPa ⁇ s or more and 600 mPa ⁇ s or less is preferable, and one having 50 mPa ⁇ s or more and 400 mPa ⁇ s or less More preferable.
• alginate (A-1) alginate sodium salt is preferable.
• alginate (A-2) As an alginate having a viscosity of less than 50 mPa ⁇ s at 20 ° C. of a 1% by mass aqueous solution, one having 5 mPa ⁇ s or more and less than 50 mPa ⁇ s is preferable, and one having 10 mPa ⁇ s or more and less than 50 mPa ⁇ s More preferable.
• alginate (A-2) alginate sodium salt is preferable.
• the coating property and the enteric property can be further improved.
• the content of the component (A) is 5 to 85% by mass based on the coating composition (solid content: when stated as solid content, the ratio to the total amount of components excluding the solvent, the ratio in the coating film The same as in the above), more preferably 10 to 80% by mass (solids), still more preferably 10 to 70% by mass (solids), and still more preferably the range of 10 to 60% by mass (solids) .
• the content of the component (A) is at least the lower limit of the above range, good enteric property can be obtained, and when the content is at most the upper limit, good coating property can be obtained.
• the content of the component (A) means the amount of sodium alginate, and when the component (A) is an alginate other than sodium alginate, it means the amount converted to the amount of sodium alginate. It shall be.
• the content of potassium alginate is multiplied by 0.92
• the content of ammonium alginate is 1.03.
• the multiplied value be the content of the component (A). The same applies to the mass ratio to the component (A-1), the component (A-2) and other components described later.
• the content is preferably 5 to 85% by mass (solid content), more preferably 10 to 60% by mass (solid content), relative to the coating composition, and 20 to 50
• the range of mass% (solid content) is more preferable.
• the content is preferably 85% by mass (solid content) or less, more preferably 5 to 50% by mass (solid content), more preferably 10 to 40%, based on the coating composition.
• the range of% (solid content) is more preferable. When the content is in the above range, the enteric property is improved and the coating property is improved.
• (A-1) alginate as (A) alginate.
• the coating property is good, and the formed coating film can be provided with high acid resistance.
• the coating performance can be further improved while maintaining the enteric property.
• the use of two alginates having different viscosities, such as (A-1) alginate and (A-2) alginate, is not merely adjustment of the viscosity of the coating solution, but is enteric and coatability From the point of view, two types of alginate are selected.
• the weight ratio (A-1): (A-2) ((A-1) / (A-2)) is preferably 1: 5 to 10: 1 (0.2 to 10), and 1: 3 to 5: 1 (0.33-5) is more preferred, and 1: 1.8-3: 1 (0.56-3) is even more preferred.
• the viscosity of alginate is measured using a rotary viscometer (BM type). If the viscosity is less than 200 mPa ⁇ s, rotor no. The viscosity of 200 mPa ⁇ s or more and less than 1,000 mPa ⁇ s using A 2 mass% aqueous solution is measured on 20 degreeC and 30 rpm conditions using 2, and let the value after 60 seconds be a measured value.
• BM type rotary viscometer
• the viscosity of alginate is approximately proportional to the molecular weight of alginate.
• the weight average molecular weight (Mw) of (A-1) is 800,000 or more, preferably 800,000 or more and less than 3,000,000, and more preferably 800,000 or more and less than 19,000.
• the weight average molecular weight (Mw) of (A-2) is 200,000 or more and less than 800,000, and preferably 300,000 or more and less than 800,000.
• GPC gel permeation chromatography
• (B) Divalent cation As the divalent cation, magnesium ion and calcium ion are preferably included, and calcium ion is more preferable.
• the divalent cation can be contained in the coating composition of the present invention by containing a metal salt containing a divalent cation.
• food materials such as calcium chloride, calcium lactate, calcium glutamate, calcium citrate, calcium gluconate, magnesium chloride, calcium hydroxide, magnesium sulfate, milk casein, bittern, seawater etc. may be mentioned.
• calcium chloride, calcium lactate and magnesium chloride can be suitably used.
• the content (content ratio) of the component (B) is preferably 0.005 to 0.10 mass% (solid content) with respect to the coating composition, and more preferably 0.01 to 0.08 mass% (solid content). Preferably, 0.03 to 0.06% by mass (solid content) is more preferable.
• the content of the component (B) can be calculated by multiplying the actual amount of metal salt containing divalent cation by the ratio of divalent cation contained in the compound.
• calcium ion in calcium chloride dihydrate is 27.27% by mass
• calcium ion in calcium lactate pentahydrate is 13.00% by mass
• magnesium ion in magnesium chloride hexahydrate is 11.96
• the content of the component (B) can be calculated by multiplying the amount used as the metal salt by the ratio of these amounts.
• the content of divalent cations can be confirmed using methods and equipment commonly used in the scientific and industrial fields. Examples of the method include inductively coupled plasma emission analysis, inductively coupled plasma mass spectrometry, electron beam microanalyzer, X-ray photoelectron spectroscopy, secondary ion mass spectrometry, ion chromatography, atomic absorption spectrometry, and the like. It is not limited.
• the content mass ratio of the component (B) to the component (A) represented by (B) / (A) ⁇ 100 is 0.015 to 0.25, preferably 0.02 to 0.20, and 0.06 -0.20 is more preferable, and 0.09-0.16 is the most preferable.
• the above content ratio is less than 0.015 or exceeds 0.25, the resulting coating film is likely to be deteriorated and has a low durability, and the tablet having such a coating film is preserved It is less stable.
• plasticizer As a plasticizer, surfactants such as sucrose fatty acid ester, glycerin fatty acid ester, monoglycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyhydric alcohols such as glycerin, propylene glycol, polyethylene glycol, glucose , Fructose, glucose, sucrose, sugars such as sucrose, sorbitol, maltitol, mannitol, erythritol, sugar alcohols such as xylitol, dodecanol, tridecanol, tetradecanol, pentadecanol, hexadecanol, heptadecanol, octadecanol Fatty acids such as higher alcohols such as hexadecyl alcohol, isostearyl alcohol, 2-octyl dodecanol (preferably having a carbon number of 6 to 22), and medium-chain fatty acid esters such
• the content of the component (C) is preferably 0.1 to 70% by mass (solid content), more preferably 2 to 50% by mass (solid content), based on the coating composition.
• the content of the component (C) is preferably 0.1 to 70% by mass (solid content), more preferably 2 to 50% by mass (solid content), based on the coating composition.
• the content mass ratio of the component (C) to the component (A) represented by (C) / (A) is preferably in the range of 0.001 to 3, more preferably 0.05 to 3, and 0.05 to 2 Is particularly preferred.
• the content mass ratio of the component (B) to the component (C) represented by (B) / (C) ⁇ 100 is preferably 0.02 to 5, more preferably 0.04 to 1.6, 0 More preferably, .06 to 1.6. Within the above range, the stability of the coating film is further improved.
• the coating composition of the present invention may contain a film forming component other than the component (A).
• a film-forming component (D) a water-soluble polymer is preferable, and specific examples thereof include natural water-soluble polysaccharides such as gelatin, pectin, curdlan, pullulan, gum arabic, xanthan gum and gellan gum, hydroxypropyl methylcellulose, carboxymethyl cellulose Examples thereof include water-soluble cellulose derivatives such as sodium and hydroxypropyl cellulose, agar, chitosan, tamarind seed gum, locust bean gum, polyvinyl alcohol, and aqueous dispersion of ethyl cellulose. These can be used singly or in appropriate combination of two or more.
• a component selected from gelatin, curdlan, pullulan, gum arabic, xanthan gum, gellan gum, hydroxypropyl methylcellulose and hydroxypropyl cellulose is preferred from the viewpoint of the coating property and the combination with the component (A).
• the content of the component (D) is preferably 1 to 80% by mass (solid content), more preferably 5 to 75% by mass (solid content) based on the coating composition.
• the content is in the above range, the effect of the component (D) can be obtained more.
• the content is more than the above range, there is a possibility that the enteric property is affected.
• the content mass ratio represented by (A) :( D) ((A) / (D)) is preferably 1:10 to 20: 1 (0.1 to 20), 1: 5 to 20 1 (0.2 to 20) is more preferable, and 1: 1 to 10: 1 (1 to 10) is more preferable.
• the content mass ratio represented by (A) :( D) ((A) / (D)) is preferably 1:10 to 20: 1 (0.1 to 20), 1: 5 to 20 1 (0.2 to 20) is more preferable, and 1: 1 to 10: 1 (1 to 10) is more preferable.
• the content mass ratio represented by (A) :( D) ((A) / (D)) is preferably 1:10 to 20: 1 (0.1 to 20), 1: 5 to 20 1 (0.2 to 20) is more preferable, and 1: 1 to 10: 1 (1 to 10) is more preferable.
• the film performance is particularly high under acidic conditions, while maintaining the coatability and the beauty of the appearance.
• the coating composition may contain (E) fine particles.
• the component (E) include talc, calcium stearate, silicon dioxide and titanium oxide. These may be used alone or in combination of two or more.
• the particle size of the fine particles is 0.01 to 50 ⁇ m, preferably 0.1 to 20 ⁇ m. The particle size is measured by a laser diffraction type particle size distribution measuring apparatus (dry type measurement).
• the content of the component (E) is preferably 1 to 80% by mass (solid content), more preferably 3 to 60% by mass (solid content), and 5 to 40% by mass (solid content) based on the coating composition. More preferable.
• the content in the above range the effect containing the component (E) can be further obtained, and when the content is more than the above range, the film forming property may be affected.
• the coating composition of the present invention may contain, in addition to the components (A) to (E), one or more components, which are generally used in the coating composition, in appropriate amounts.
• an optional component an antifoamer, a coloring agent, etc. are mentioned.
• antifoaming agent examples include glycerin fatty acid ester, dimethylpolysiloxane, dimethylpolysiloxane / silicon dioxide mixture, hydrous silicon dioxide, silicon dioxide and the like, which may be used alone or in combination of two or more. it can.
• coloring agent for example, asenyakutannin powder, turmeric extract, yellow ferric oxide, orange essence, brown iron oxide, carbon black, caramel, carmine, carotene solution, ⁇ -carotene, licorice extract, gold foil, black iron oxide
• a coloring agent for example, asenyakutannin powder, turmeric extract, yellow ferric oxide, orange essence, brown iron oxide, carbon black, caramel, carmine, carotene solution, ⁇ -carotene, licorice extract, gold foil, black iron oxide
• Light anhydrous silicic acid, titanium oxide, ferric oxide, food blue 1, food yellow 4, food yellow 4 aluminum lake, food yellow 5, food red 2, food red 3, food red 102 examples thereof include sodium hydroxide, copper chlorophine sodium, copper chlorophyll, green leaf extract extract, medicinal charcoal, riboflavin butyrate, riboflavin, green tea powder, riboflavin sodium phosphate and the like.
• the coating composition of the present invention can contain an organic solvent such as water or ethanol within the range not impairing the effects of the present invention.
• the solvent content in the coating composition is appropriately selected in the range of 1 to 98% by mass, preferably 50 to 98% by mass, and more preferably 70 to 96% by mass, with respect to the entire coating composition.
• the coating in the present invention is to form a film by applying or spraying a coating solution on the surface of a coated material, or immersing the coated material in the coating solution to dry and solidify. Shall be included.
• a coating preparation can be obtained by using the above-mentioned coating composition to form a coating film composed of the coating composition on a substrate.
• the form of the material to be coated and the dosage form are not particularly limited, and a coating film is formed on a solid surface such as tablets, powders, fine granules, granules, hard capsules, soft capsules, powders, etc. It is sufficient that the shape can be formed.
• the tablet may have a single layer or two or more layers. Among these, from the viewpoint of exhibiting more enteric property, it is preferable to use a tablet.
• the size of the tablet is not particularly limited, and the diameter of the tablet is preferably 5 to 14 mm ⁇ , more preferably 7 to 12 mm ⁇ , from the viewpoint of ease of handling and swallowability of the tablet.
• the tablet weight per tablet is suitably about 150 to 700 mg.
• Active ingredients such as a foodstuff and a pharmaceutical, etc. are mentioned.
• Active ingredients include lactic acid bacteria, cysteine, iron, proteins such as antibodies and lactoferrin, peptides, ATP-2Na and the like, and these can be used singly or in appropriate combination of two or more.
• high molecular weight components such as proteins and water insoluble components are preferable.
• the coating film means the case where only a coating film (hereinafter sometimes referred to as a main coating film) obtained using the coating composition according to the present invention is formed.
• a main coating film obtained using the coating composition according to the present invention is formed.
• the main coating film is meant, in addition to the main coating film, when a pre-coating film or a top coating film to be described later is formed, the entire coating film including these is also meant.
• the main coating film, the precoating film and the top coating film may be one layer or two or more layers respectively.
• the main coating film may be coated with a coating solution having different proportions of (A) alginate and (B) divalent cations, and may have two or more layers.
• A alginate
• B divalent cations
• the coating film (main coating film) formed from the coating composition of the present invention contains the above-mentioned component (A), but it is dried by directly drying an aqueous solution of alginic acid as described later To form a film. Under acidic conditions, this water-soluble film has the property that a monovalent cation displaces a hydrogen ion, changes to alginic acid to form an insoluble film, and dissolves in neutral to alkaline.
• the coating composition of the present invention and the coating film formed from the coating composition are enteric, that is, they can be dissolved in the stomach without being dissolved in the stomach and the coated material can reach the intestine. It is a thing.
• enteric coated preparation having a coated material and an enteric coated film formed from the above-mentioned coating composition by coating the coated material with the enteric coating composition of the present invention Can.
• enteric refers to an agent that delivers a functional ingredient to the intestine.
• the test is carried out according to the method of dissolution test method of the Japanese Pharmacopoeia method, and the dissolution rate of less than 50% (preferably less than 30%) in 2 hours with gastric juice equivalent dissolution test solution (pH 1.2), equivalent to intestinal fluid In the dissolution test solution (pH 6.8), the dissolution rate is 70% or more in 2 hours.
• the thickness of the main coating film is not particularly limited, but is preferably 5 ⁇ m to 2.5 mm, more preferably 10 ⁇ m to 2.0 mm, and still more preferably 50 ⁇ m to 1.5 mm.
• the thickness of the coating film is not particularly limited, but is preferably 5 ⁇ m to 2.5 mm, more preferably 10 ⁇ m to 2.0 mm, and still more preferably 50 ⁇ m to 1.5 mm.
• the coating being applied to the substrate by the coating composition of the present invention, and the thickness of the coating film can be confirmed using methods and equipment commonly used in the scientific and industrial fields. Although the method of following (i) and (ii) is illustrated as the method, for example, it is not limited to these methods.
• (I) The section of the coating preparation cut with a cutter is observed with a digital microscope or a scanning electron microscope to measure the thickness of the coating film at a plurality of locations, and the average value of the measured values is taken as the layer thickness.
• the coating preparation is noninvasively applied according to the measurement method of each system using near infrared / middle infrared / far infrared imaging system, terahertz imaging system, OCT imaging system (optical coherence tomography)
• the distribution is measured, and the average value of the measured values is taken as the layer thickness.
• the weight per unit area of the main coating film is not particularly limited, but is preferably 3.0 to 25 mg / cm 2 , and 5.0 to 20 mg / cm. 2 is more preferable.
• the weight per unit area of the main coating film is 3.0 mg / cm 2 or more, sufficient gastric resistance over time can be obtained, and by setting the weight to 25 mg / cm 2 or less, elution in the intestinal environment The quality is good.
• the main coating film is preferably 0.5 to 20% by mass, more preferably 1 to 15% by mass, relative to the coating preparation.
• the content is preferably 10 to 60% by mass, more preferably 15 to 50% by mass.
• content (solid content) of said each component in a main coating film is the same as the said coating composition.
• the to-be-coated material may be provided with a pre-coating which is a lower layer of the main coating film.
• the pre-coating composition is not particularly limited, but a composition containing the above (D) film-forming component can be suitably used.
• the content of the component (D) in the precoating composition is preferably 10 to 90% by mass (solid content) in the composition, and more preferably 20 to 80% by mass (solid content).
• the precoating composition may contain (C) a plasticizer.
• component (C) When the component (C) is contained, its content is preferably 1 to 40% by mass (solid content) in the composition.
• the thickness of the precoating film is not particularly limited, but is preferably 1 to 500 ⁇ m, and more preferably 10 to 300 ⁇ m. By setting the thickness of the precoating film to 1 ⁇ m or more, sufficient gastric resistance over time can be obtained, and by setting the thickness to 500 ⁇ m or less, the dissolution in the intestinal environment becomes good.
• the weight per unit area of the pre-coating film is not particularly limited, but is preferably 0.5 ⁇ 10mg / cm 2, 1 ⁇ 5mg / cm 2 Gayori preferable.
• the weight per unit area of the pre-coated membrane is 0.5 mg / cm 2 or more, sufficient gastric resistance over time can be obtained, and by setting it to 10 mg / cm 2 or less, elution in the intestinal environment is possible. The quality is good.
• the precoating film is preferably 0.5 to 20% by mass, more preferably 1 to 12% by mass, relative to the coating preparation.
• the content is preferably 10 to 60% by mass, more preferably 15 to 50% by mass.
• an overcoat may be further applied on the main coating film.
• the overcoat coating composition is not particularly limited, but a composition containing the components (C), (D) and (E) can be used. Further, as an optional component, carnauba, wax, beeswax, shellac and the like can be contained.
• the thickness of the overlying coating film, the weight per unit area, and the mass ratio to the coating preparation are not particularly limited, but can be in the same range as the above precoating film.
• the preferable content (content ratio) of each component in the entire coating film is as follows.
• the following content refers to the content in the main coating film when the coating film is only the main coating film, and when the coating film contains one or both of the precoating film and the top coating film, the main content is the main content.
• the coating film and the content in the entire coating film including these coating films are shown.
• the suitable component of each component and physicochemical properties (1% aqueous solution viscosity, molecular weight, particle diameter) other than the preferable content are the same as the respective components in the coating composition.
• optional components that can be contained are the same as in the coating composition.
• the content of the alginate (A) is preferably 5 to 85% by mass, more preferably 10 to 80% by mass, still more preferably 10 to 70% by mass, and still more preferably 10 to 60% by mass based on the total mass of the coating film. Is more preferable.
• the content of the component (A) is in the above range, good enteric properties and coating properties can be obtained.
• the content is preferably 5 to 85% by mass, more preferably 10 to 60% by mass, and further preferably 20 to 50% by mass with respect to the mass of the entire coating film. preferable.
• the content is preferably 85% by mass or less, more preferably 5 to 50% by mass, and still more preferably 10 to 40% by mass, based on the mass of the entire coating film. .
• the enteric property is improved and the stability of the coating film is further improved.
• the mass ratio (A-1) of the alginate (A-1) to the alginate (A-2): (A-2) ((A-1) / (A-2)) is 1: 5 to 10 1 (0.2 to 10) is preferable, 1: 3 to 5: 1 (0.33 to 5) is more preferable, and 1: 1.8 to 3: 1 (0.56 to 3) is more preferable.
• the content of the divalent cation (B) is preferably 0.005 to 0.10% by mass, more preferably 0.01 to 0.08% by mass, and more preferably 0.03 to 0% with respect to the total mass of the coating film. More preferably, .06% by mass.
• Examples of the method include inductively coupled plasma emission analysis, inductively coupled plasma mass spectrometry, electron beam microanalyzer, X-ray photoelectron spectroscopy, secondary ion mass spectrometry, ion chromatography, atomic absorption spectrometry, and the like. It is not limited.
• the content of the plasticizer (C) is preferably 0.1 to 70% by mass, and more preferably 2 to 50% by mass, with respect to the total mass of the coating film.
• the content of the film-forming component (D) is preferably 1 to 80% by mass, and more preferably 5 to 75% by mass, based on the total mass of the coating film. When the content of the component (D) is in the above range, good enteric properties can be obtained.
• the content of the fine particles (E) is preferably 1 to 80% by mass, more preferably 3 to 60% by mass, and still more preferably 5 to 40% by mass, based on the total mass of the coating film.
• the solvent contained in coating composition may remain
• the content is preferably 30% by mass or less, more preferably 10% by mass or less, and even more preferably not contained (0% by mass), based on the total mass of the coating film.
• the content mass ratio of the component (C) to the component (A) represented by (C) / (A) in the entire coating film is preferably in the range of 0.001 to 3, and more preferably 0.05 to 3, 0.15 to 2 is particularly preferred. By setting the contained mass ratio in the above range, the film performance under acidic condition becomes higher, and the stability of the coating film is further improved.
• the content mass ratio of the component (B) to the component (C) represented by (B) / (C) ⁇ 100 is preferably 0.02 to 5, more preferably 0.04 to 1.6, 0 More preferably, .06 to 1.6.
• the content mass ratio represented by (A) :( D) ((A) / (D)) is preferably 1:10 to 20: 1 (0.1 to 20), and 1: 5 to 20: 1 (0.2 to 20) is more preferable, and 1: 1 to 10: 1 (1 to 10) is more preferable.
• the ratio of the precoating film to the entire coating film is not particularly limited, but is preferably 5 to 60% by mass, and more preferably 10 to 50% by mass with respect to the mass of the entire coating film.
• the ratio of the top coating film to the entire coating film is not particularly limited, but is preferably 5 to 60% by mass, and more preferably 10 to 50% by mass with respect to the total mass of the coating film.
• the thickness of the entire coating film is not particularly limited, but is preferably 5 ⁇ m to 2.5 mm, more preferably 10 ⁇ m to 2.0 mm, and still more preferably 50 ⁇ m to 1.5 mm.
• the thickness of the entire coating film is not particularly limited, but is preferably 5 ⁇ m to 2.5 mm, more preferably 10 ⁇ m to 2.0 mm, and still more preferably 50 ⁇ m to 1.5 mm.
• the weight per unit area of the entire coating film is not particularly limited, but is preferably 3.0 to 25 mg / cm 2 , and 5.0 to 20 mg / cm 2 is more preferable.
• the weight per unit area of the entire coating film is 3.0 mg / cm 2 or more, sufficient gastric resistance over time can be obtained, and by setting the weight to 25 mg / cm 2 or less, elution in the intestinal environment is possible. The quality is good.
• the entire coating film is preferably 0.5 to 20% by mass, more preferably 1 to 15% by mass, relative to the coating preparation.
• the content is preferably 10 to 60% by mass, more preferably 15 to 50% by mass.
• the main coating film appropriately contains the components (D) and (E) in addition to the components (A), (B) and (C) as described above. can do.
• the component (C) is preferably a sugar such as glucose, fructose glucose liquid sugar or sucrose, or a sugar alcohol such as sorbitol, maltitol, mannitol, erythritol or xylitol, and the component (D) is gelatin, pectin, pullulan, Gum arabic, hydroxypropyl methylcellulose, polyvinyl alcohol are preferred.
• the component (E) talc and titanium oxide are preferable.
• the coating composition can be obtained by mixing the above-mentioned essential components, and the coating preparation sprays the coating composition as it is or the coating solution to which water is added, It can obtain by forming a coating film in the surface of a to-be-coated thing by drying. Since the coating composition of the present invention is aqueous, coating with water is possible, and a coating film is formed.
• the method of preparing the coating solution for the main coating film (hereinafter sometimes referred to as the main coating solution) is not particularly limited as long as the respective components can be finally mixed on the surface of the article to be coated.
• the main coating solution is not particularly limited as long as the respective components can be finally mixed on the surface of the article to be coated.
• it is a one-component type which prepares a solution containing all of (A) component, (B) component and optional components beforehand, it is a two-component type or a multi-component which divides each component into a plurality of solutions. It may be liquid.
• An example of the one-pack type main coating solution is one containing a coating composition and water, and the water content of the coating solution is preferably 50 to 98% by mass, and more preferably 70 to 96% by mass. Moreover, you may contain organic solvents, such as ethanol, in the range which does not impair the effect of this invention.
• Examples of the two-component and multi-component main coating solutions include, but are not limited to, the following methods.
• (I) A solution containing the component (A) and a method for preparing a solution containing the component (B) (ii) A solution containing the component (A) and an optional component, and a solution containing the component (B) Method
• (Iii) A solution containing the component (A), a method for preparing a solution containing the component (B) and the optional component iv) a solution containing the component (A) and the optional component, a component (B) and the optional component Method (v) of individually preparing the solution containing the solution, solution containing the (A) component and the component (B), method of preparing the solution containing the optional component (vi) solution containing the (A) component, and (B) component
• the coating machine is not particularly limited, and a pan coating machine, a fluidized bed coating machine, a rolling coating machine, a spouted bed apparatus with a draft tube, a spray drying granulator etc. can be used, but usually used in the technical field As long as it is
• the coating method is not particularly limited, for example, there is a method of forming a film on the surface of the coated material by spraying the main coating solution onto the material to be coated and drying by heating.
• the main coating solution can be heated as appropriate, the temperature is preferably 30 to 80 ° C., and the drying temperature is preferably 40 to 80 ° C.
• the addition rate of the main coating solution is preferably 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 the object to be coated is dipped and dried in the main coating solution. Drying is preferably carried out until the amount of water in the coating preparation becomes 0.1 to 20% by mass.
• each solution may be mixed before being sent to the coating machine, and after being sent to the coating machine, applied or sprayed onto the object to be coated. It may be mixed just before the Furthermore, each solution can also be mixed in the process of applying or spraying in a coating machine. For example, the following methods are exemplified, but not limited thereto.
• a precoating film is formed on the surface of the article to be coated by spraying the above precoating composition as it is or a coating solution to which water is added and drying it.
• the formation method of a pre-coating film can employ
• a top coating film is formed on the surface of the article to be coated by spraying the above top coating composition as it is or a coating solution to which water is added and drying it.
• the method of forming the overlying coating film may employ the same apparatus and method as those for forming the main coating film.
• the coating may be a full coating covering the entire surface of the article to be coated or a partial coating covering a part.
• partially coated tablets can be obtained by immersing only one layer of the two-layered tablet in the coating solution.
• Examples 1 to 34, Comparative Examples 1 to 4 The following uncoated tablets were prepared, and coating solutions having the compositions shown in Tables 1 to 11 below were prepared, and the uncoated tablets were coated by the following method to prepare coated tablets.
• the content ratio of the component (B) the calcium content in calcium chloride dihydrate is 27.27% by mass
• the calcium content in calcium lactate pentahydrate is 13.00% by mass
• magnesium chloride hexahydrate The magnesium content in the hydrate was calculated as 11.96% by mass.
• Uncoated tablet The following raw materials were mixed, and tableting was performed using a tableting machine to give tablets (300 mg, ⁇ 9.0 mm, thickness 5.3 mm).
• Preparation of Coating Solution (1) Preparation of pre-coating solution All components were mixed and stirred according to the compositions described in Tables 1 to 10, and uniformly dissolved to obtain a pre-coating solution. The right column in the table shows solid content (%) (the same applies hereinafter). (2) Preparation of Main Coating Solution According to the coating solution composition described in Tables 1 to 10, component (A) and component (B) were dispersed in a part of water and uniformly dissolved to prepare solution A. Next, the other components were dispersed in the remaining water to prepare a solution B, which was added to the solution A, and the mixture was further mixed and stirred to obtain a main coating solution.
• [coating] (1) Pre-coating Using a coating machine (High Coater FZ-Lab manufactured by Freund Corporation), 45 g of a pre-coating solution (25 ° C.) is sprayed at an average of 4 g / min against 200 g of uncoated tablet, Pre-coated at ° C. After spraying, it was dried at about 45 ° C. for 2 minutes to obtain a coating preparation (tablet).
• the thickness of the precoating film was 10 to 30 ⁇ m, and the weight per unit area of the precoating film was in the range of 1.0 to 2.0 mg / cm 2 . In Example 32, only a main coating described later was performed without forming a precoating film.
• the film thickness of the entire coating film including the precoating film and the main coating film is 80 to 230 ⁇ m
• the weight per unit area of the film of the entire coating film including the precoating film and the main coating film is 7 to 21 mg / It was in the range of cm 2 and the water content in the coating preparation was 2 to 7% by mass.
• Examples 35 to 37 Uncoated tablets were prepared in the same manner as in Example 1, and a two-component coating solution having the composition shown in Table 11 was prepared, and the uncoated tablets were coated by the following method to prepare coated tablets.
• Preparation of two-component coating solution (1) Preparation of Main Coating Solution I The component (B) was dispersed in a portion of water according to the composition described in Table 11, and was uniformly dissolved to prepare a solution A. Next, the other components were dispersed in the remaining water to prepare a solution B, which was added to the above solution A and mixed and stirred to obtain a main coating solution I.
• Example 38 Uncoated tablets were prepared in the same manner as in Example 1, and a two-component coating solution of the composition shown in Table 11 was prepared, and the uncoated tablets were coated by the following method to prepare coated tablets.
• Preparation of two-component coating solution (1) Preparation of Main Coating Solution I The component (B) was dispersed in a portion of water according to the composition described in Table 11, and was uniformly dissolved to prepare a solution A. Next, the other components were dispersed in the remaining water to prepare a solution B, which was added to the above solution A and mixed and stirred to obtain a main coating solution I.
• Coating I layer (main coating first layer) Using a coating machine (High Coater FZ-Lab, manufactured by Freund Corporation), 45 g of main coating solution I (25 ° C.) is sprayed at an average of 4 g / min to 200 g of uncoated tablet, coating at a product temperature of about 50 ° C. Applied. After spraying, it was dried at about 45 ° C. for 2 minutes.
• the thickness of the film of Coating I was 10 to 30 ⁇ m, and the weight per unit area of the film of Coating I was in the range of 1.5 to 2 mg / cm 2 .
• Coating II layer 200 g of main coating solution II (60 ° C.) is sprayed at an average of 4 g / min to 200 g of uncoated tablet using a coating machine (High Coater FZ-Lab, manufactured by Freund Corporation), and coating is performed at a product temperature of about 50 ° C. Applied. After spraying, it was dried at about 45 ° C. for 2 minutes to obtain a coating preparation (tablet).
• the thickness of the film of Coating II was 50 to 200 ⁇ m, and the weight per unit area of the film of Coating II was in the range of 6.5 to 9 mg / cm 2 .
• the film thickness of the entire coating film including Coatings I and II is 80 to 230 ⁇ m, and the weight per unit area of the film of the entire coating film including Coatings I and II is within the range of 8 to 11 mg / cm 2
• the water content in the coating preparation was 2 to 7% by mass.
• lactoferrin determination The determination method of lactoferrin conformed to the method of the draft 9th edition food additives bill. ⁇ Quantitative> The sampling solution 2 hours after the above-mentioned elution test was used as a sample solution. 20 ⁇ L each of the sample solution and the standard solution of three concentrations were weighed, and liquid chromatography was performed under the following operating conditions. The lactoferrin peak area of each standard solution was measured to prepare a calibration curve. The lactoferrin concentration in the sample solution is determined from the calibration curve and the lactoferrin area of the sample solution, and the lactoferrin elution rate relative to 100 mg of lactoferrin / tablet is determined by the following equation.
• Chromatography condition detector Ultraviolet absorptiometer (measurement wavelength: 280 nm)
• Column packing agent 5 ⁇ m butylated polyvinyl alcohol polymer gel for liquid chromatography (Shodex Asahipak C4P-50 4D)
• Column tube Stainless steel tube guard column with an inner diameter of 4.6 mm and a length of 15 cm: Shodex Asahipak C4P-50G 4A
• Column temperature 35 ° C
• Mobile phase B Acetonitrile / sodium chloride solution (3 ⁇ 100) mixture (50:50) containing 0.03 w / v% trifluoroacetic acid Concentration gradient A linear concentration gradient from A: B (50:50) to (0: 100) was performed for 25 minutes.
• Coating property was evaluated based on the following evaluation criteria. ⁇ : The coating is uniformly applied, no chipping, peeling is observed, and the coating surface has gloss. ⁇ : Coating is uniformly made, chipping and peeling are hardly seen, but the surface of the coating is slightly rough. ⁇ : some tablets show missing coating.

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