WO2016035756A1 - Préparation enrobée et son procédé de production - Google Patents

Préparation enrobée et son procédé de production Download PDF

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Publication number
WO2016035756A1
WO2016035756A1 PCT/JP2015/074731 JP2015074731W WO2016035756A1 WO 2016035756 A1 WO2016035756 A1 WO 2016035756A1 JP 2015074731 W JP2015074731 W JP 2015074731W WO 2016035756 A1 WO2016035756 A1 WO 2016035756A1
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WIPO (PCT)
Prior art keywords
coating
mass
layer
enteric
component
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PCT/JP2015/074731
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English (en)
Japanese (ja)
Inventor
千晶 高橋
あゆみ 松野
木津　典生
Original Assignee
ライオン株式会社
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Application filed by ライオン株式会社 filed Critical ライオン株式会社
Priority to CN201580046747.3A priority Critical patent/CN106794253B/zh
Priority to KR1020177002830A priority patent/KR102392313B1/ko
Priority to JP2016546638A priority patent/JP6642438B2/ja
Publication of WO2016035756A1 publication Critical patent/WO2016035756A1/fr

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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
    • 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
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • 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
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • 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
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to a coating preparation used as a food, a medicine and the like and a method for producing the same.
  • ingredients that do not dissolve under the pH conditions (acidic) in the stomach but dissolve under the pH conditions (neutral to alkaline) of the small intestine such as methacrylic acid polymers Compounds, shellac, zein and the like are common.
  • methacrylic acid polymer compounds are limited to pharmaceutical use and cannot be used for food.
  • shellac and zein are also used for food applications, but spraying using an organic solvent is common.
  • the use of a water-soluble film agent capable of coating with water in consideration of the environment for food applications has been desired.
  • the present invention has been made in view of the above circumstances, and it is possible not only to dissolve in the stomach but to dissolve in the intestine, and to ensure that the coated active ingredient reaches the intestine more reliably, and to prevent deterioration over time as much as possible. It aims at providing the coating formulation which can be suppressed, and is excellent also in storage stability, and its manufacturing method.
  • the present inventors previously proposed an alginate enteric coating preparation using water as a solvent in consideration of the environment (Japanese Patent Application No. 2013-046697).
  • the enteric preparation provided with this coating has advantages such as very good entericity immediately after coating (elution suppression under acidic conditions, dissolution under neutral conditions).
  • elution inhibition property under acidic conditions may decrease over time even though the appearance of the coating film does not change.
  • the cause is not clear, but it is presumed to be that a very fine structural change has occurred since the elution suppression property has decreased despite the fact that there is no change in the appearance of the coating film.
  • the inventors applied a pre-coating as the lower layer of the enteric coating film for this fine structural change, and surprisingly, suppression of elution under acidic conditions over time. It was found that the deterioration of the property can be improved.
  • the pre-coating with respect to the enteric coating film is generally carried out in order to improve the peeling of the film due to poor compatibility between the enteric coating film and the tablet.
  • the present inventors have newly found that pre-coating has a function of protecting the enteric coating film using the above-mentioned alginate from deterioration over time and is effective for improving the storage stability of the coating preparation. It has come.
  • the present invention provides the following coating preparation and method for producing the same.
  • An object to be coated a lower layer containing a polymer compound having a viscosity of less than 300 mPa ⁇ s at 25 ° C. of a 6% by mass aqueous solution (A) formed thereon, and formed on the lower layer
  • a coating preparation comprising an enteric coating layer containing an alginate and (C) a plasticizer.
  • the component (A) is selected from the group consisting of hydroxypropylmethylcellulose, pectin, curdlan, pullulan, hydroxypropylcellulose, polyvinyl alcohol, and gum arabic.
  • the outer side of the enteric coating layer (D) is selected from the group consisting of gelatin, pectin, curdlan, pullulan, gum arabic, xanthan gum, gellan gum, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and hydroxypropylcellulose. 6.
  • (A) A step of forming a lower layer by spraying a solution containing a polymer compound having a viscosity of less than 300 mPa ⁇ s at 25 ° C.
  • the coating preparation of the present invention not only does it dissolve in the stomach but dissolves in the intestine, so that the coated active ingredient can surely reach the intestine, and even when stored for a long period of time, it suppresses dissolution under acidic conditions.
  • the coating formulation which can suppress the fall of property as much as possible and is excellent also in storage stability can be provided.
  • the coating preparation of the present invention has an object to be coated, a lower layer formed thereon, and an enteric coating layer formed on the lower layer.
  • One or more intermediate layers may be formed between the soluble coating layer and the outermost layer.
  • those having a coating object, a lower layer formed on the surface of the coating object, and an enteric coating layer formed on the surface of the lower layer are preferable.
  • the outermost layer can be formed on the outer side of the enteric coating layer as necessary, as long as the enteric quality is not affected.
  • enteric refers to an agent that delivers a functional component to the intestine.
  • dissolution test method of Japanese Pharmacy Method
  • dissolution rate was less than 50% (preferably 30% or less) in 2 hours in dissolution test solution (pH 1.2) corresponding to gastric juice.
  • Dissolution rate of 70% or more in 2 hours with dissolution test solution (pH 6.8).
  • the object to be coated is not particularly limited, and examples thereof include active ingredients such as foods and pharmaceuticals.
  • active ingredients such as foods and pharmaceuticals.
  • examples include lactic acid bacteria, cysteine, iron, proteins such as antibodies and lactoferrin, peptides, ATP-2Na, and the like, and these can be used alone or in combination of two or more. Among them, it is suitable for high molecular weight components such as proteins and water insoluble components.
  • the shape and dosage form of the object to be coated are not particularly limited, and there are no particular limitations on tablets, powders, fine granules, granules and the like.
  • the tablet may be a single layer or two or more layers. Among these, it is preferable to set it as a tablet from the point which exhibits enteric property more.
  • the size of the tablet is not particularly limited, and the tablet diameter is preferably 5 to 14 mm ⁇ and more preferably 7 to 12 mm ⁇ from the viewpoint of easy handling and swallowability.
  • the tablet mass per tablet is suitably about 150 to 700 mg.
  • the lower layer of the present invention is a layer formed prior to an enteric coating layer containing an alginate described later, for example, a layer formed on the surface of an object to be coated.
  • an enteric coating layer containing an alginate described later for example, a layer formed on the surface of an object to be coated.
  • the present invention by forming a lower layer between the object to be coated and the enteric coating layer, it is possible to prevent a temporal decrease in the elution suppression effect under acidity during storage. Thereby, the storage stability (elution suppression property under acidic conditions) of the coating preparation in which the enteric coating layer is formed can be remarkably improved.
  • the lower layer will be described in detail.
  • the lower layer contains (A) a polymer compound whose viscosity at 25 ° C. in a 6% by mass aqueous solution is less than 300 mPa ⁇ s.
  • the component (A) is not particularly limited, and specific examples include hydroxypropylmethylcellulose, pectin, curdlan, pullulan, hydroxypropylcellulose, polyvinyl alcohol, and gum arabic. One species can be used alone, or two or more species can be used in appropriate combination. In the present invention, hydroxypropylmethylcellulose can be particularly preferably used.
  • the amount of the component (A) is not particularly limited, but is preferably 1 to 10% by mass, more preferably 3 to 8% by mass, based on the entire precoating composition (lower layer composition).
  • the amount of the component (A) is not particularly limited, but is preferably 1 to 10% by mass, more preferably 3 to 8% by mass, based on the entire precoating composition (lower layer composition).
  • the lower layer may contain (E) a plasticizer as necessary.
  • (E) Component includes 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 Sugars such as liquid sugar, sucrose, sugar alcohols such as sorbitol, maltitol, mannitol, erythritol, and xylitol, dodecanol, tridecanol, tetradecanol, pentadecanol, hexadecanol, heptadecanol, octadecanol, hexadecyl Examples include higher alcohols such as alcohol, isostearyl alcohol, 2-octyldodecanol (preferably having 6 to 22 carbon atoms),
  • the amount of the component (E) is not particularly limited, but is preferably 0.3 to 6% by mass, more preferably 0.8 to 5% by mass, based on the entire lower layer composition.
  • the lower layer composition may contain (F) fine particles.
  • the fine particles By blending the fine particles, it is possible to prevent peeling of the coating film due to adhesion between tablets during the coating process.
  • the component (F) include talc, calcium stearate, silicon dioxide, titanium oxide, and the like, which can be used alone or in combination of two or more.
  • the particle diameter of the fine particles is 0.01 to 50 ⁇ m, preferably 0.1 to 20 ⁇ m. The particle size is measured with a laser diffraction particle size distribution measuring device (dry measurement).
  • the blending amount of the component (F) is preferably 0.05 to 7% by mass, more preferably 0.1 to 5% by mass, and still more preferably 0.3 to 3% by mass with respect to the entire lower layer composition.
  • the above lower layer composition may contain an organic solvent such as water and ethanol.
  • the amount of the solvent in the lower layer 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 lower layer composition.
  • the thickness of the lower layer is not particularly limited, but is preferably 1 to 200 ⁇ m, more preferably 2 to 100 ⁇ m.
  • the lower layer adhesion amount is preferably 0.6 to 10.5 mg / 300 mg (0.2 to 3.5% by mass) with respect to 300 mg of uncoated tablet, and 1.5 to 7. More preferably, it is 5 mg / 300 mg (0.5 to 2.5 mass%).
  • the content is preferably 0.5 to 30% by mass, and more preferably 1 to 25% by mass.
  • the effect of the present invention (that is, preventing the elution suppression effect under acidic conditions from decreasing with time) is effectively obtained. be able to.
  • a tablet can be produced in an appropriate production time by setting the thickness and adhesion amount of the lower layer to be equal to or lower than the upper limit of the above range.
  • the method for forming the lower layer is not particularly limited, and a known method can be adopted.
  • a method of forming a film on the surface of the object to be coated by spraying a predetermined coating solution on the object to be coated and drying by heating is exemplified.
  • the coating solution can be appropriately heated, and the temperature is preferably 30 to 80 ° C. and the drying temperature is preferably 40 to 80 ° C.
  • the addition rate of the coating solution is preferably 1 to 5 g / min with respect to a dry air volume of 1 m 3 / min.
  • the lower layer is not limited to a single layer, and a plurality of layers may be formed as necessary.
  • the coating machine is not particularly limited, and a pan coating machine, a fluidized bed coating machine, a rolling coating machine or the like can be used.
  • the enteric coating layer of the present invention is an enteric layer formed on the outside of the lower layer and contains (B) an alginate and (C) a plasticizer.
  • (B) Alginic acid salt As the alginic acid salt, monovalent alginate such as sodium salt, potassium salt and ammonium salt, and alginic acid water-soluble salt are preferable.
  • the alginate the following (B-1) 1% by mass aqueous solution having a viscosity at 20 ° C. of 50 mPa ⁇ s or more, (B-2) 1% by mass aqueous solution having a viscosity at 20 ° C. of less than 50 mPa ⁇ s: Can be used, and one kind can be used alone, or two or more kinds can be used in appropriate combination.
  • a 1% by weight aqueous solution having a viscosity at 20 ° C. of 50 mPa ⁇ s or more is preferably 50 mPa ⁇ s or more and 600 mPa ⁇ s or less, more preferably 50 mPa ⁇ s or more and 400 mPa ⁇ s or less. preferable.
  • the blending amount is preferably 0.1 to 5% by weight, more preferably 0.5 to 4% by weight, and more preferably 1 to 4% by weight of the entire coating composition. Further preferred.
  • the blending amount is preferably 0.1 to 5% by weight, more preferably 0.5 to 4% by weight, and more preferably 1 to 4% by weight of the entire coating composition. Further preferred.
  • Alginates having a viscosity of 1% by weight aqueous solution at 20 ° C. of less than 50 mPa ⁇ s are preferably from 5 mPa ⁇ s to less than 50 mPa ⁇ s, and preferably from 10 mPa ⁇ s to less than 50 mPa ⁇ s. More preferred.
  • B-2 As the alginate, sodium alginate is preferable.
  • the blending amount is preferably 5% by mass or less, more preferably 0.1 to 4% by mass, and more preferably 0.1 to 2.5% by mass of the entire coating composition.
  • a range is more preferred. By making a compounding quantity below the upper limit of the said range, enteric property improves and coating property becomes favorable.
  • the blending amount of the component (B) (that is, the total amount of the component (B-1) and the component (B-2)) is preferably 0.1 to 10% by mass of the entire coating composition. Further, the range of 1 to 7% by mass is more preferable, and the range of 1.5 to 5% by mass is more preferable. When the blending amount is not more than the upper limit of the above range, good enteric properties (elution suppression under acidic conditions) can be obtained.
  • (B-1) alginate As (B) alginate, it is preferable to use (B-1) alginate as (B) alginate.
  • the coating property is good and high acid resistance can be imparted to the formed coating film.
  • the coating performance can be further improved while maintaining enteric properties.
  • the use of two types of alginate having different viscosities such as (B-1) alginate and (B-2) alginate is not simply the adjustment of the viscosity of the coating solution, but enteric and coating properties. From the viewpoint of the above, two types of alginate are selected.
  • the mass ratio of (B-1) :( B-2) ((B-1) / (B-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 the alginate is measured using a rotary viscometer (BM type). Viscosity with a viscosity of less than 200 mPa ⁇ s 1 and a viscosity of 200 mPa ⁇ s or more and less than 1,000 mPa ⁇ s is rotor No. 2 is used to measure a 1% by mass aqueous solution under the conditions of 20 ° C. and 30 rpm, and the value after 60 seconds is taken as the measurement value.
  • BM type rotary viscometer
  • the viscosity of alginate is almost proportional to the molecular weight of alginate.
  • the weight average molecular weight (Mw) of (B-1) is 800,000 or more, preferably from 80 to less than 3 million, more preferably from 80 to less than 1.9 million.
  • the weight average molecular weight (Mw) of (B-2) is from 200,000 to less than 800,000, preferably from 300,000 to less than 800,000.
  • the measuring method of the gel chromatography of the weight average molecular weight (Mw) of the alginate of this invention is shown below.
  • Preparation alginate concentration of the sample is to this sample was dissolved in mobile phase so that 0.1 wt% (0.1M (mol / L) NaNO 3 solution).
  • Plasticizer is a component blended for the purpose of lowering the surface tension of the coating composition and imparting flexibility to the coating layer.
  • surfactants such as sucrose fatty acid ester, glycerin fatty acid ester, monoglycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, etc., glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol and the like
  • Sugars such as monohydric alcohol, glucose, fructose glucose liquid sugar, sucrose, sugar alcohols such as sorbitol, maltitol, mannitol, erythritol, xylitol, dodecanol, tridecanol, tetradecanol, pentadecanol, hexadecanol, heptadecanol, heptadecanol Higher alcohols such as octadecanol, hex
  • the blending amount of the component (C) is preferably 0.3 to 5% by mass, more preferably 0.5 to 3% by mass, based on the entire coating composition.
  • the mass ratio represented by (C) / (B) is preferably in the range of 0.05 to 3.0, more preferably 0.1 to 2.0, still more preferably 0.15 to 1.5, and 15 to 1.1 is particularly preferred.
  • the coating composition of the present invention may contain a film forming component (D) other than the component (B).
  • D Gelatin, pectin, curdlan, pullulan, gum arabic, xanthan gum, gellan gum, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, agar, chitosan, tamarind seed gum, locust bean gum, polyvinyl Alcohol, ethylcellulose aqueous dispersion, etc. are mentioned. These can be used individually by 1 type or in combination of 2 or more types.
  • components selected from gelatin, pectin, curdlan, pullulan, gum arabic, xanthan gum, gellan gum, hydroxypropylmethylcellulose, sodium carboxymethylcellulose and hydroxypropylcellulose are from the viewpoint of coating properties and combination with component (B). preferable.
  • the blending amount of the component (D) is preferably 0.1 to 7% by mass, more preferably 0.2 to 5% by mass, and still more preferably 0.3 to 3% by mass based on the entire coating composition.
  • the content ratio represented by (B) :( D) ((B) / (D)) is preferably 1: 3 to 1: 0.05 (0.33 to 20), and preferably 1: 1. ⁇ 1: 0.1 (1-10) is more preferred, and 1: 0.8-1: 0.2 (1.25-5) is even more preferred.
  • Fine particles may be blended in the coating composition. By blending the fine particles, it is possible to prevent peeling of the coating film due to adhesion between tablets during the coating process.
  • the component (F) include talc, calcium stearate, silicon dioxide, titanium oxide, and the like, which can be used alone or in combination of two or more.
  • the particle diameter of the fine particles is 0.01 to 50 ⁇ m, preferably 0.1 to 20 ⁇ m. As in the case of the lower layer composition, the particle size is measured with a laser diffraction particle size distribution analyzer (dry measurement).
  • the blending amount of the component (F) is preferably 0.05 to 7% by mass, more preferably 0.1 to 5% by mass, and still more preferably 0.3 to 3% by mass based on the entire coating composition.
  • the said coating composition does not contain bivalent metal ions, such as a copper ion, barium ion, and calcium ion. This is because the alginate is cross-linked and gelled, and the coating property is deteriorated. In other words, when monovalent alginate is reacted with a divalent cation to crosslink, the dried membrane is insoluble in water, but the viscosity becomes too high due to gelation, so a fine liquid spray and on the tablet It becomes difficult to spread. As a result, it is difficult to form a uniform film, the appearance is deteriorated, and the elution property may vary.
  • the allowable range of the divalent metal ion is preferably 0.5 mol or less, more preferably 0.25 mol or less, and still more preferably 0.1 mol or less with respect to 1 mol of the alginate monomer.
  • the above-mentioned coating composition can be blended with a component usually used in a coating composition singly or in appropriate amounts.
  • a component usually used in a coating composition singly or in appropriate amounts.
  • optional components include antifoaming agents and coloring agents.
  • antifoaming agent examples include glycerin fatty acid ester, dimethylpolysiloxane, dimethylpolysiloxane / silicon dioxide mixture, hydrous silicon dioxide, silicon dioxide and the like, and these may be used alone or in combination of two or more. it can.
  • colorant examples include asenyakutannin powder, turmeric extract, yellow ferric oxide, orange essence, brown iron oxide, carbon black, caramel, carmine, carotene solution, ⁇ -carotene, licorice extract, gold leaf, black iron oxide , Light anhydrous silicic acid, titanium oxide, iron sesquioxide, edible blue No. 1, edible yellow No. 4, edible yellow No. 4 aluminum lake, edible yellow No. 5, edible red No. 2, edible red No. 3, edible red No. 102, Examples include sodium hydroxide, copper chlorofin sodium, copper chlorophyll, green leaf extract, medicinal charcoal, riboflavin butyrate, riboflavin, green tea powder, and sodium riboflavin phosphate.
  • the coating composition of the present invention can contain an organic solvent such as water and ethanol.
  • the amount of the solvent 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 thickness of the enteric coating layer is not particularly limited, but is preferably 5 to 1,000 ⁇ m, more preferably 10 to 500 ⁇ m.
  • the amount of the enteric coating layer attached is preferably 1.5 to 60 mg / 300 mg (0.5 to 20% by mass) with respect to 300 mg of the uncoated tablet, and preferably 3 to 45 mg / 300 mg (1 It is more preferable that the content be ⁇ 15% by mass.
  • the content is preferably 10 to 60% by mass, more preferably 15 to 50% by mass.
  • the thickness of the enteric coating layer and the adhesion amount By setting the thickness of the enteric coating layer and the adhesion amount to be equal to or more than the lower limit of the above range, a preparation excellent in elution suppression ability under acidic conditions can be obtained. On the other hand, when the amount of the enteric coating layer deposited is not more than the upper limit of the above range, it can be kept within an appropriate production time.
  • the relationship between the thickness of the lower layer and the thickness of the enteric coating layer is not particularly limited, and there is no problem as long as each is within the appropriate range described above.
  • the method for forming the enteric coating layer is not particularly limited, and a known method can be adopted.
  • a method of forming a film on the surface of the object to be coated by spraying a predetermined coating solution on the object to be coated on which the lower layer is formed and drying by heating is exemplified.
  • the coating solution can be appropriately heated, and the temperature is preferably 30 to 80 ° C. and the drying temperature is preferably 40 to 80 ° C.
  • the addition rate of the 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 in a coating solution and dried. Drying is preferably performed until the water content in the coating preparation is 0.1 to 20% by mass, particularly 0.5 to 5% by mass.
  • the coating machine is not particularly limited, and a pan coating machine, a fluidized bed coating machine, a rolling coating machine or the like can be used.
  • An appropriate intermediate layer may be formed between the lower layer and the coating layer as long as the effects of the present invention are not impaired.
  • a shellac coating film and a hardened oil / fat coating film can be formed.
  • the outermost layer can be formed using the (D) film-forming component on the outside of the enteric coating layer as necessary. Thereby, an external appearance, mouthfeel, and a taste can be changed.
  • component (D) gelatin, pectin, curdlan, pullulan, gum arabic, xanthan gum, gellan gum, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, agar, chitosan, tamarind seed gum, locust bean gum, polyvinyl alcohol, Examples thereof include an aqueous ethyl cellulose dispersion. These can be used individually by 1 type or in combination of 2 or more types.
  • components selected from gelatin, pectin, curdlan, pullulan, gum arabic, xanthan gum, gellan gum, hydroxypropyl methylcellulose, sodium carboxymethylcellulose and hydroxypropylcellulose are preferable from the viewpoint of coating properties.
  • the thickness of the outermost layer is not particularly limited, but is preferably 1 to 200 ⁇ m, more preferably 2 to 100 ⁇ m.
  • the amount of the outermost layer is preferably 0.6 to 10.5 mg / 300 mg (0.2 to 3.5% by mass) with respect to 300 mg of the uncoated tablet, 1.5 to 7 More preferably, it is 5 mg / 300 mg (0.5 to 2.5% by mass).
  • the content is preferably 1 to 30% by mass, more preferably 2 to 25% by mass.
  • the above outermost layer composition may contain an organic solvent such as water and ethanol as long as the effects of the present invention are not impaired.
  • the amount of the solvent in the outermost layer composition is appropriately selected in the range of 1 to 98% by mass, preferably 50 to 98% by mass, more preferably 70 to 96% by mass with respect to the entire outermost layer composition. .
  • the method for forming the outermost layer is not particularly limited, and a known method can be adopted.
  • a method of forming a film on the surface of the object to be coated by spraying a predetermined coating solution on the object to be coated on which the lower layer and the enteric coating layer are formed and drying by heating is exemplified.
  • the coating solution can be appropriately heated, and the temperature is preferably 30 to 80 ° C. and the drying temperature is preferably 40 to 80 ° C.
  • the addition rate of the 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 in a coating solution and dried. Drying is preferably performed until the water content in the coating preparation is 0.1 to 20% by mass, particularly 0.5 to 5% by mass.
  • the coating machine is not particularly limited, and a pan coating machine, a fluidized bed coating machine, a rolling coating machine or the like can be used.
  • the coating formulation of this invention sprays the solution containing the high molecular compound whose viscosity in 25 degreeC of (A) 6 mass% aqueous solution is less than 300 mPa * s on to-be-coated object, A step of forming a lower layer by drying, a step of spraying a solution containing (B) an alginate and (C) a plasticizer on the outside of the lower layer, and forming an enteric coating layer by drying, and as required Accordingly, it can be produced by spraying a solution containing the film-forming component (D) and drying it to form the outermost layer.
  • the details of each step are as described above, but the composition of the coating solution to be used, the coating conditions, and the like can be appropriately set within a range not impairing the effects of the present invention, and are not particularly limited.
  • the coating solution for forming each of the lower layer, the enteric coating layer and, if necessary, the outermost layer can be obtained by mixing the above-described essential components. Then, by using each of the above coating solutions, a coating preparation having both good enteric properties and excellent storage stability by sequentially forming a lower layer, an enteric coating layer and, if necessary, an outermost layer on the object to be coated Can get. Moreover, since the coating solution of each layer uses water as a solvent, a water-soluble film is formed respectively.
  • the enteric coating layer formed from the above coating composition contains the component (B), but as described above, the aqueous alginate solution is directly dried to form a water-soluble film.
  • This water-soluble film has the property that, under acidic conditions, monovalent cations are replaced with hydrogen ions to form alginic acid to form an insoluble film, and further, it dissolves in neutral to alkaline conditions.
  • the enteric coating layer formed from the above coating composition is enteric, that is, has the property of being “dissolvable in the intestine without being dissolved in the stomach and allowing the article to be coated to reach the intestine”.
  • An enteric coating preparation in which the coating film is enteric is obtained.
  • a lower layer containing the component (A) is formed under the enteric coating layer, and the lower layer functions as a base for protecting the enteric coating layer from deterioration over time. It can suppress as much as possible that the elution suppression property under acidic condition falls, and the storage stability of a coating formulation can be improved significantly.
  • Lactoferrin Morinaga Milk Industry Hihatsu Extract Powder: Maruzen Pharmaceutical Co., Ltd.
  • Lactose "Lactose granule” manufactured by Freund Sangyo Co., Ltd.
  • Crystalline cellulose “Theolas FD-101” manufactured by Asahi Kasei Chemicals Corporation Sodium carboxymethyl cellulose: Nichirin Chemical Industries, “ECC-FA” Sucrose fatty acid ester: “Ryoto Sugar Ester S-370F” manufactured by Mitsubishi Chemical Foods Corporation Fine silicon dioxide: “Carplex FPS-500” manufactured by DSL Japan
  • a coating solution for forming a lower layer, an enteric coating layer, and an outermost layer having the compositions shown in Tables 2 to 4 below was prepared by the following procedure.
  • a lower layer, an enteric coating layer, and, if necessary, an outermost layer were sequentially formed on the surface of the uncoated tablet prepared above using each of the coating solutions prepared above to prepare a coating preparation (tablet).
  • Conditions for coating each layer are as follows.
  • the coating preparation obtained above was evaluated for entericity by the following procedure immediately after coating and after being stored for 4 months under the conditions of 50 ° C. and 75% RH. The storage stability was confirmed by comparison. Moreover, the external appearance (coating property) of the preparation immediately after coating was evaluated.
  • Pectin Dainippon Pharmaceutical Co., Ltd., “Classic AF701” Polyvinyl alcohol: manufactured by Nippon Synthetic Chemical Co., Ltd., “Polyvinyl alcohol EG-22P” Gum arabic: Made by Nippon Powder Chemical Co., Ltd., “Gum arabic” Hydroxypropyl cellulose: Hydroxypropyl cellulose: Nippon Soda Co., Ltd., “HPC-SSL” Pullulan: “Pullulan” manufactured by Hayashibara Co., Ltd. Sucrose: Dainippon Meiji Sugar Co., “Sucrose” [Enteric coating layer] Glycerin: “Glycerin (food additive)” manufactured by Sakamoto Pharmaceutical Co., Ltd.
  • Silica fine silicon dioxide
  • Talc “Crown Talc PP” manufactured by Matsumura Sangyo Co., Ltd.
  • Hydroxypropyl methylcellulose “Metroze SE-06” manufactured by Shin-Etsu Chemical Co., Ltd.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Preparation (AREA)
  • General Preparation And Processing Of Foods (AREA)
  • Jellies, Jams, And Syrups (AREA)

Abstract

La présente invention concerne : une préparation enrobée, qui ne peut pas être dissoute dans l'estomac mais peut être dissoute dans l'intestin, afin de garantir qu'un principe actif enrobé atteigne l'intestin, et qui peut empêcher de manière efficace sa détérioration avec le temps, et qui présente une excellente stabilité au stockage ; et un procédé de production de la préparation enrobée. L'invention concerne une préparation enrobée comprenant : une substance à enrober ; une sous-couche qui est formée sur la substance et qui contient un composé polymère (A) ayant une propriété telle qu'une solution aqueuse à 6 % en masse possède une viscosité inférieure à 300 mPa · s à 25 °C ; et une couche de revêtement gastro-résistant qui est formée sur la sous-couche et qui contient un sel d'alginate (B) et un plastifiant (C).
PCT/JP2015/074731 2014-09-03 2015-08-31 Préparation enrobée et son procédé de production WO2016035756A1 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107865969A (zh) * 2016-09-28 2018-04-03 狮王株式会社 包衣组合物、包衣制剂及其制造方法
WO2019031550A1 (fr) * 2017-08-09 2019-02-14 ライオン株式会社 Composition de revêtement, film de revêtement et préparation de revêtement et son procédé de production
JP2019052101A (ja) * 2017-09-13 2019-04-04 アリメント工業株式会社 多層被覆製剤
KR20210018030A (ko) 2019-08-06 2021-02-17 라이온 가부시키가이샤 락토페린 함유 장용정 및 그 제조 방법
WO2022014601A1 (fr) * 2020-07-13 2022-01-20 キリンホールディングス株式会社 Comprimés pelliculés

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108740371B (zh) * 2018-04-04 2021-07-30 广州智特奇生物科技股份有限公司 肠溶包被材料、采用该包被材料包被的氧化锌及其制备方法
JP7370224B2 (ja) * 2019-11-08 2023-10-27 ライオン株式会社 ラクトフェリン含有腸溶製剤
JP7375581B2 (ja) 2020-01-28 2023-11-08 株式会社デンソー 電池パック

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59193831A (ja) * 1983-04-18 1984-11-02 Sankyo Co Ltd 腸溶性製剤の製造法
JPS62263124A (ja) * 1986-05-07 1987-11-16 Sankyo Co Ltd 経口投与製剤
JPS63503515A (ja) * 1986-06-19 1988-12-22 カラーコン　インコーポレイテツド 薬剤、食料品及び菓子類の製品の水性のフイルムコーテイングのためのポリデキストローズを基剤としたコーテイング
JP2000514406A (ja) * 1996-06-06 2000-10-31 ビフォーダン アクティーゼルスカブ アルギン酸から成る経口投与製剤用腸溶性被膜
JP2007530683A (ja) * 2004-03-31 2007-11-01 ビーピーエスアイ ホールディングス，インコーポレーテッド 経口摂取可能な基材の腸溶性コーティング
WO2011125798A1 (fr) * 2010-03-31 2011-10-13 持田製薬株式会社 Préparation solide aisément administrable
JP2013519686A (ja) * 2010-02-12 2013-05-30 センシエント カラーズ エルエルシー 腸溶性コーティング組成物ならびにその製造法および使用法
WO2014032741A1 (fr) * 2012-08-27 2014-03-06 Evonik Industries Ag Composition pharmaceutique ou nutraceutique gastrorésistante présentant de la résistance vis-à-vis de l'influence de l'éthanol

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002193792A (ja) 2000-12-25 2002-07-10 Lion Corp フィルムコーティング錠剤及びエロージョン防止組成物
CN101371836A (zh) * 2007-08-23 2009-02-25 珠海天翼医药技术开发有限公司 帕罗西汀肠溶缓释组合物
WO2011111027A2 (fr) * 2010-03-11 2011-09-15 Dexcel Pharma Technologies Ltd. Formulation de comprimé oral dispersible à libération retardée
JP2013142086A (ja) * 2012-01-08 2013-07-22 Yasuyuki Sugano 陽イオン性歯周病予防剤
CN102813629A (zh) * 2012-08-29 2012-12-12 湖北龙翔药业有限公司 一种酒石酸沃尼妙林预混剂的制备方法
JP6304234B2 (ja) * 2013-03-08 2018-04-04 ライオン株式会社 コーティング組成物、コーティング製剤及びその製造方法
CN104857520B (zh) * 2015-04-29 2017-12-29 南京圣诺生物科技实业有限公司 一种海藻酸钠包衣液组合物及包衣方法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59193831A (ja) * 1983-04-18 1984-11-02 Sankyo Co Ltd 腸溶性製剤の製造法
JPS62263124A (ja) * 1986-05-07 1987-11-16 Sankyo Co Ltd 経口投与製剤
JPS63503515A (ja) * 1986-06-19 1988-12-22 カラーコン　インコーポレイテツド 薬剤、食料品及び菓子類の製品の水性のフイルムコーテイングのためのポリデキストローズを基剤としたコーテイング
JP2000514406A (ja) * 1996-06-06 2000-10-31 ビフォーダン アクティーゼルスカブ アルギン酸から成る経口投与製剤用腸溶性被膜
JP2007530683A (ja) * 2004-03-31 2007-11-01 ビーピーエスアイ ホールディングス，インコーポレーテッド 経口摂取可能な基材の腸溶性コーティング
JP2013519686A (ja) * 2010-02-12 2013-05-30 センシエント カラーズ エルエルシー 腸溶性コーティング組成物ならびにその製造法および使用法
WO2011125798A1 (fr) * 2010-03-31 2011-10-13 持田製薬株式会社 Préparation solide aisément administrable
WO2014032741A1 (fr) * 2012-08-27 2014-03-06 Evonik Industries Ag Composition pharmaceutique ou nutraceutique gastrorésistante présentant de la résistance vis-à-vis de l'influence de l'éthanol

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107865969A (zh) * 2016-09-28 2018-04-03 狮王株式会社 包衣组合物、包衣制剂及其制造方法
JP2018053059A (ja) * 2016-09-28 2018-04-05 ライオン株式会社 コーティング組成物ならびにコーティング製剤及びその製造方法
WO2019031550A1 (fr) * 2017-08-09 2019-02-14 ライオン株式会社 Composition de revêtement, film de revêtement et préparation de revêtement et son procédé de production
JPWO2019031550A1 (ja) * 2017-08-09 2020-09-03 ライオン株式会社 コーティング組成物、コーティング膜、コーティング製剤及びその製造方法
JP7111104B2 (ja) 2017-08-09 2022-08-02 ライオン株式会社 コーティング組成物、コーティング膜、コーティング製剤及びその製造方法
JP2019052101A (ja) * 2017-09-13 2019-04-04 アリメント工業株式会社 多層被覆製剤
JP7046323B2 (ja) 2017-09-13 2022-04-04 アリメント工業株式会社 多層被覆製剤
KR20210018030A (ko) 2019-08-06 2021-02-17 라이온 가부시키가이샤 락토페린 함유 장용정 및 그 제조 방법
JP2021024821A (ja) * 2019-08-06 2021-02-22 ライオン株式会社 ラクトフェリン含有腸溶錠及びその製造方法
JP7339057B2 (ja) 2019-08-06 2023-09-05 ライオン株式会社 ラクトフェリン含有腸溶錠及びその製造方法
WO2022014601A1 (fr) * 2020-07-13 2022-01-20 キリンホールディングス株式会社 Comprimés pelliculés

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