CN106794253A - Coated preparation and its manufacture method - Google Patents
Coated preparation and its manufacture method Download PDFInfo
- Publication number
- CN106794253A CN106794253A CN201580046747.3A CN201580046747A CN106794253A CN 106794253 A CN106794253 A CN 106794253A CN 201580046747 A CN201580046747 A CN 201580046747A CN 106794253 A CN106794253 A CN 106794253A
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- coated
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- mass
- coated preparation
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- 238000000034 method Methods 0.000 title claims abstract description 29
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- 238000009505 enteric coating Methods 0.000 claims abstract description 45
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims abstract description 42
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- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 15
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- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- DQMUQFUTDWISTM-UHFFFAOYSA-N O.[O-2].[Fe+2].[Fe+2].[O-2] Chemical compound O.[O-2].[Fe+2].[Fe+2].[O-2] DQMUQFUTDWISTM-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 108010055615 Zein Proteins 0.000 description 1
- ZIALXKMBHWELGF-UHFFFAOYSA-N [Na].[Cu] Chemical compound [Na].[Cu] ZIALXKMBHWELGF-UHFFFAOYSA-N 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000012735 amaranth Nutrition 0.000 description 1
- 239000004178 amaranth Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229910001422 barium ion Inorganic materials 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 239000006229 carbon black Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000012732 erythrosine Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000009408 flooring Methods 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- 239000010977 jade Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 150000002711 medium chain fatty acid esters Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229920002414 procyanidin Polymers 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000009923 sugaring Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 229940052016 turmeric extract Drugs 0.000 description 1
- 235000020240 turmeric extract Nutrition 0.000 description 1
- 239000008513 turmeric extract Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- General Preparation And Processing Of Foods (AREA)
- Jellies, Jams, And Syrups (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Present invention aim at a kind of coated preparation of offer and its manufacture method, the coated preparation is not dissolved in stomach and dissolved in enteron aisle, the active ingredient being coated more reliably is reached enteron aisle, and suppress as much as possible through when cracking, excellent storage stability.The coated preparation has：It is coated thing, the lower floor being formed on and the enteric coatings being formed on the lower floor, macromolecular compound of viscosity of (A) the 6 mass % aqueous solution at 25 DEG C less than 300mPas is contained in the lower floor, and the enteric coatings contain (B) alginate and (C) plasticizer.
Description
Technical field
The present invention relates to the coated preparation and its manufacture method that are used as food, pharmaceuticals etc..
Background technology
A kind of following Enteric formulations are needed, with the functional component such as protein such as lactic acid bacteria and enzymes, is passed through
Prevent the decomposition in stomach from keeping its structure, it is reached enteron aisle so as to play the active ingredient of high functionality, said preparation is in stomach
It is interior insoluble and dissolved in enteron aisle, active ingredient is reached in enteron aisle.
As in order that active ingredient reaches the diaphragm of enteron aisle, typically having insoluble under pH conditions (acidity) under one's belt
And the composition dissolved under the pH conditions (neutral~alkalescence) of small intestine, such as metha crylic macromolecular compound, shellac, jade
Rice alcohol soluble protein etc..
But, metha crylic macromolecular compound is only limitted to pharmaceuticals purposes, can not be used for food.The opposing party
Although face, shellac, zeins can be used for food applications, but generally use organic solvent and sprayed.Even
In food applications, it is also desirable to using water-soluble film considering environment, being coated with water.
Additionally, as prior art literature involved in the present invention, there is following documents.
Prior art literature
Patent document
【Patent document 1】JP 2002-193792 publications
The content of the invention
Invent technical task to be solved
The present invention in view of said circumstances and make, it is described its object is to provide a kind of coated preparation and its manufacture method
Coated preparation is not dissolved in stomach and dissolved in enteron aisle, the active ingredient being coated more reliably is reached intestines
Road, and suppress as much as possible through when cracking, storage stability is also excellent.
Solve the means of technical task
The present inventor, previously considers environment, it is proposed that be used as the alginate enteric coatings preparation (Patent of solvent with water
No. 2013-046697).The Enteric formulations of coating are implemented, with after being just coated, enteric solubility (suppresses under acidity
Stripping property under dissolution, neutrality) extraordinary advantage.But, in further research after which, the occasion learnt
Under, although the outward appearance of coating membrane is not changed in, process over time, dissolution under acid condition can inhibition drop
It is low.Although reason is unclear, can according to the dissolution although the outward appearance of coating membrane is almost unchanged can inhibition drop
It is low to generate very small structure change speculating.
Therefore, present inventor has performed deeper into investigation, as a result find, relative to the small structure change, implement
Precoating as enteric coatings film lower floor when, unexpectedly improve through when suppress the problem that acid lower stripping property is reduced.
It is caused with the intermiscibility deterioration of tablet in order to improve enteric coatings film to the precoating of enteric coatings film
Film stripping and the means generally implemented, the present inventor's new discovery：The precoating has been played can be protected using above-mentioned sea
The function of the deterioration of the enteric coatings film of alginates, and it is effective for improving the storage stability of coated preparation
, so as to complete the present invention.
Therefore, the present invention provides following coated preparations and its manufacture method.
[1] a kind of coated preparation, it is characterised in that have：Thing is coated, what is be formed on contains (A) the 6 mass % aqueous solution
The lower floor of the macromolecular compound of viscosity at 25 DEG C less than 300mPas, and be formed on the lower floor and contain (B) sea
The enteric coatings of alginates and (C) plasticizer.
[2] coated preparation according to [1], (A) composition is selected from hydroxypropyl methyl cellulose, pectin, curdlan, Propiram
The group of polysaccharide, hydroxypropyl cellulose, polyvinyl alcohol and Arabic gum composition.
[3] coated preparation according to [2], (A) composition is hydroxypropyl methyl cellulose.
[4] coated preparation described in any one according to [1]~[3], (B) composition is (B-1) the 1 mass % aqueous solution at 20 DEG C
Viscosity for more than 50mPas alginate.
[5] coated preparation according to [4], wherein, it is also further viscous at 20 DEG C containing (B-2) the 1 mass % aqueous solution
Alginate of the degree less than 50mPas.
[6] coated preparation described in any one according to [1]~[5], wherein, further have, outside enteric coatings
It is fine that (D) gelatin, pectin, curdlan, pulullan polysaccharide, Arabic gum, xanthans, gellan gum, hydroxypropyl methyl are contained in side
The outermost layer of the macromolecular compound selected in the group of dimension element, sodium carboxymethylcellulose and hydroxypropyl cellulose composition.
[7] coated preparation according to [6], (D) composition is hydroxypropyl methyl cellulose.
[8] a kind of manufacture method of coated preparation, it is characterised in that include：Sprayed containing (A) 6 matter by being coated thing
The solution and work that is dry and forming lower floor of viscosity macromolecular compound less than 300mPas of the amount % aqueous solution at 25 DEG C
Sequence, and enteric coatings are formed to the solution of the outside spraying containing (B) alginate and (C) plasticizer of the lower floor and drying
The operation of layer.
[9] manufacture method of the coated preparation according to [8], wherein, also further contain by above-mentioned enteric coatings
The spraying of layer outside contains (D) gelatin, pectin, curdlan, pulullan polysaccharide, Arabic gum, xanthans, gellan gum, hydroxypropyl
The solution of the macromolecular compound selected in the group of ylmethyl cellulose, sodium carboxymethylcellulose and hydroxypropyl cellulose composition is simultaneously
Dry and form outermost operation.
Invention effect
By coated preparation of the invention, a kind of coated preparation can be provided, not dissolved in stomach and dissolved in enteron aisle,
The active ingredient being coated can be not only set to reach enteron aisle really, and under the occasion for preserving for a long time, it is also possible to as much as possible
Suppress dissolution under acid condition can inhibition decline, and storage stability is also excellent.
Specific embodiment
The present invention is described in detail below.
Coated preparation of the invention have be coated thing, the lower floor being formed on and the enteric solubility being formed on the lower floor
Coatings, the coated preparation can also be coated between thing and lower floor or, between enteric coatings and outermost layer formed 1 layer
Intermediate layer above.Wherein, preferably be coated thing, this be coated on the surface of thing formed lower floor and the lower floor table
The coated preparation of enteric coatings is formed on face.In the present invention, do not influenceing in the range of enteric solubility quality, can be according to need
Outermost layer is formed in the outside of enteric coatings.Additionally, " enteric solubility " in the present invention is to instigate functional components to reach
The preparation of enteron aisle.Refer to be tested according to the method for the dissolution test method of Japanese Pharmacopoeia, in the dissolution test equivalent to gastric juice
2 hours dissolution rates are less than 50% (suitable is less than 30%) in liquid (pH1.2), in the dissolution test liquid equivalent to intestinal juice
(pH6.8) dissolution rate of 2 hours is more than 70% in.
(I) it is coated thing
In the present invention, it is coated thing and is not particularly limited, active ingredients such as food, pharmaceuticals etc. can be enumerated.Breast can for example be enumerated
The protein such as sour bacterium, cysteine, iron, antibody and lactoferrin, peptide, ATP-2Na etc., they can be used alone a kind of or suitable
When being used in combination of two or more.Wherein it is advisable with the high molecular weight components such as protein and water insoluble active ingredient.
It is coated the shape of thing, formulation to be not particularly limited, is not particularly limited in tablet, powder, fine grained agent, granule
Deng.Tablet can be that individual layer can also be more than two layers.Wherein, from from the point of view of preferably playing enteric solubility, preferably
Tablet.The size of tablet is not particularly limited, from tablet be easily processed and the property swallowed from the viewpoint of, the diameter preferably 5 of tablet
~14mm Φ, more preferably 7~12mm Φ.Additionally, the quality per tablet is suitably for 150~700mg or so.
(II) lower floor
Lower floor of the invention is the layer formed before the enteric coatings containing alginate described later, for example, in quilt
The layer formed on the surface of coatingss.In the present invention, lower floor is formed between thing and enteric coatings by being coated, can
In preventing from preserving, suppress acid lower result of extraction through when reduction.Can be significantly improved by this and form enteric solubility
The storage stability (dissolution can inhibition) under acidity of the coated preparation of coatings.Hereinafter, lower floor is described in detail.
Macromolecular compound of viscosity of (A) the 6 mass % aqueous solution at 25 DEG C less than 300mPas is contained in lower floor.On
State (A) composition to be not particularly limited, used as concrete example, can illustrate hydroxypropyl methyl cellulose, pectin, curdlan, Pu Lu
Blue polysaccharide, hydroxypropyl cellulose, polyvinyl alcohol and Arabic gum etc., they can be used alone it is a kind of or it is appropriately combined two kinds with
On use.In the present invention, particularly suitable use hydroxypropyl methyl cellulose.
The combined amount of above-mentioned (A) composition is not particularly limited, whole relative to pre-coating (lower floor's composition)
Body, preferably 1~10 mass %, more preferably 3~8 mass %.By making combined amount more than the lower limit of above range, will can make
Time control is made in reasonable time.On the other hand, by making combined amount below the upper limit of above range, can be by viscosity
Control the viscosity sprayed in the preparation of Suitable coatings liquid and coating solution.
Additionally, in above-mentioned lower floor, can as needed contain (E) plasticizer.As (E) composition, sucrose fat is for example there are
The surfactants such as acid esters, fatty acid glyceride, mono-fatty acid glyceride, polyoxyethylene sorbitan fatty acid ester；Glycerine,
The polyalcohols such as propane diols, polyethylene glycol；The sugar such as glucose, HFCS, sucrose；D-sorbite, maltitol, mannitol,
The sugar alcohols such as antierythrite, xylitol；Dodecanol, tridecanol, tetradecanol, pentadecanol, hexadecanol, heptadecanol,
The higher alcohol of octadecanol, hexadecanol, isooctadecanol, 2- octyldodecanols etc. (suitable is carbon number 6~22)；Middle chain
The greases such as fatty acid ester (suitable is carbon number 6~12).They can with one kind be used alone or it is appropriately combined two kinds with
On use.In the present invention, wherein, from from the aspect of plasticization effect, preferably use glycerine.
The combined amount of above-mentioned (E) composition is not particularly limited, relative to the entirety of lower floor's composition, preferably 0.3~6 matter
Amount %, more preferably 0.8~5 mass %.By making combined amount more than the lower limit of above range, can improve under preventing acidity
Suppress result of extraction through when the effect that reduces.On the other hand, by making combined amount below the upper limit of above range, can be by
Manufacturing time is controlled in reasonable time.
(F) particulate can be mixed in lower floor's composition.By hybrid fine particles, when can prevent Cotton seeds because tablet it
Between stick together caused by coating membrane come off.As (F) composition, talcum powder, calcium stearate, silica, dioxy are for example there are
Change titanium etc., they can be used alone a kind of or appropriately combined two or more use.The particle diameter of particulate is 0.01~50 μm, preferably
0.1~20 μm.Additionally, the measure of particle diameter can be carried out using laser diffraction formula particle size distribution device (dry type measure).
(F) combined amount of composition, preferably lower floor 0.05~7 overall mass % of composition, more preferably 0.1~5 matter
Amount %, further preferred 0.3~3 mass %.By making combined amount more than the lower limit of above range, can be mixed with
The effect of (F) composition is stated, if being mixed with the upper limit more than above range, can probably be had an impact to film forming.
The organic solvents such as water, ethanol can be contained in above-mentioned lower floor's composition.Solvent mixing in lower floor's composition
Amount, relative to lower floor's composition entirety, suitably selectes, preferably 50~98 mass % in the range of 1~98 mass %, more excellent
Select 70~96 mass %.
The thickness of lower floor is not particularly limited, preferably 1~200 μm, more preferably 2~100 μm.Additionally, under the occasion of tablet,
The adhesion amount of lower floor, relative to plain piece 300mg, preferably 0.6~10.5mg/300mg (0.2~3.5 mass %), more preferably 1.5
~7.5mg/300mg (0.5~2.5 mass %).Under granule, powder, the occasion of powder, preferably 0.5~30 mass % is more excellent
Select 1~25 mass %.By making the thickness of lower floor and adhesion amount more than the lower limit of above range, this hair can be effectively obtained
Bright effect (preventing the reduction of the suppression result of extraction under the acidity along with the process of time).On the other hand, by making
The thickness and adhesion amount of lower floor can make tablet below the upper limit of above range in suitable manufacturing time.
The method for forming above-mentioned lower floor, is not particularly limited, can be using known method.Can for example enumerate by quilt
Coatingss spray specific Coating Solution and heat drying and make the method for being coated the surface membranization of thing.Coating Solution can be fitted
Work as heating, preferably 30~80 DEG C of temperature, preferably 40~80 DEG C of drying temperature.Relative to drying air quantity 1m3/ min, Coating Solution
Adding speed preferably 1~5g/min.Alternatively, it is also possible to using dry dip-coating side after thing is impregnated into Coating Solution will be coated
Method.It is preferred that by the amount of moisture drying in coated preparation to 0.1~20 mass %.Particularly preferably dry to 0.5~5 mass %.This
Outward, above-mentioned lower floor is not limited to one layer, can as needed form multilayer.
Now, seed-coating machine is not particularly limited, it is possible to use pan coater, fluidized-bed coating machine, drum type coating machine
Deng.
(III) enteric coatings
Enteric coatings of the invention are the layers with enteric solubility formed in the outside of above-mentioned lower floor, and it contains (B) sea
Alginates and (C) plasticizer.
(B) alginate
The monovalence such as alginate particular certain cancers, sylvite, ammonium salt alginate, alginic acid water soluble salt.Can be arranged as alginate
It is alginate, (B-2) 1 mass % aqueous solution of more than 50mPas to lift viscosity of (B-1) the 1 mass % aqueous solution at 20 DEG C
The alginate of viscosity at 20 DEG C less than 50mPas, can be used alone a kind of or appropriately combined two or more uses.
(B-1) viscosity of the 1 mass % aqueous solution at 20 DEG C is the preferred 50mPas of alginate of more than 50mPas
Above and below 600mPas alginate, the alginate of more preferably more than 50mPas and below 400mPas.
In the case of mixing (B-1) alginate, relative to the entirety of coated composition, combined amount preferably 0.1~5 matter
Amount %, more preferably 0.5~4 mass %, the scope of further preferred 1~4 mass %.By more than the lower limit of above range,
Can fully obtain dissolution under acidity can rejection, obtain more preferable enteric solubility.On the other hand, by the upper limit with
Under, viscosity can be controlled to the viscosity of preparation or transport, the spraying of Suitable coatings liquid.
(B-2) viscosity of the 1 mass % aqueous solution at 20 DEG C less than 50mPas the preferred 5mPas of alginate with
Upper, the alginate less than 50mPas, more preferably more than 10mPas, the alginate less than 50mPas.(B-2) marine alga
The preferred alginic acid sodium salt of hydrochlorate.
In the case of mixing (B-2) alginate, relative to coated composition entirety, combined amount preferably below 5 mass %,
More preferably 0.1~4 mass %, the scope of further preferred 0.1~2.5 mass %.By making combined amount in the upper of above range
Limit is following, and enteric solubility is improved, and coating property is good.
Additionally, the combined amount (i.e. the total amount of (B-1) composition and (B-2) composition) of (B) composition to be preferably coated composition whole
0.1~10 mass % of body.Additionally, the more preferably scope of 1~7 mass %, the scope of further preferred 1.5~5 mass %.It is logical
Crossing makes combined amount below the upper limit of above range, can obtain good enteric solubility (dissolution can inhibition) under acidity.
In the present invention, (B) alginate preferably uses (B-1) alginate.By using such certain above length
Alginate, be coated property it is good, the coating membrane of formation can be assigned with highly-acidproof.Additionally, passing through and using (B-1) alginate
(B-2) alginate, can more improve and be coated performance while enteric solubility is kept.
Alginate using (B-1) alginate as described above and the such two kinds of different viscosities of (B-2) alginate is not
Only two kinds of alginates are selected from Coating Solution viscosity is adjusted from from the viewpoint of enteric solubility and coating property.Its quality
Than (B-1)：(B-2) ((B-1)/(B-2)) preferably 1：5~10：1 (0.2~10), more preferably 1：3~5：1 (0.33~5), enters one
Step preferably 1：1.8~3：1 (0.56~3).By making mass ratio more than the lower limit of above range, the epithelium performance under acidifying is more
Height, thus it is insoluble good.By the way that below the upper limit of above range, coating property is more preferable, so further preferably.
In addition, in the present invention, the viscosimetric analysis of alginate is carried out using rotary viscosimeter (BM types).It is not enough
The viscosity of 200mPas is using rotor No.1, more than 200mPas and the viscosity less than 1,000mPas uses rotor No.2,
The 1 mass % aqueous solution is determined under conditions of 20 DEG C, 30rpm, the value after 60 seconds is taken as measured value.
The viscosity of alginate is substantially directly proportional to the molecular weight of alginate.The weight average molecular weight of such as above-mentioned (B-1)
(Mw) for more than 800,000, preferably 80~less than 3,000,000, more preferably molecular weight 80~less than 1,900,000.(B-2) weight average molecular weight
(Mw) it is more than 200,000 and less than 800,000, preferably more than 300,000 and less than 800,000.In addition, alginate of the invention is divided equally again
The gel chromatography assay method of son amount (Mw) is as follows.
(1) preparation of sample
Alginate is dissolved in mobile phase (0.1M (mol/L) NaNO3The aqueous solution) in, make alginate concentration be 0.1 matter
Amount %, in this, as sample.
Use the standard items (pulullan polysaccharide of various molecular weight：Mw=166 ten thousand, Mw=38 ten thousand, Mw=10 ten thousand, Mw=1.22 ten thousand,
Dissolved with 0.1 mass % concentration in mobile phase) it is made standard curve.
(2) GPC condition determinations
Chromatographic column：Shodex OHpak SB-806M HQ(8mmI.D.×300mmL.,13μm)
Mobile phase：0.1M(mol/L)NaNO3The aqueous solution
Flow：0.5mL/min
Temperature：40℃
Sample size：200 μ L (0.1% in mobile phase)
Detector：Differential refraction rate (RI) detector
(3) analysis method
Calibration curve formula is tried to achieve by standard curve sample, the gpc analysis result according to sample tries to achieve that to be converted into Propiram more
The weight average molecular weight (Mw) of sugar.
(C) plasticizer
Plasticizer is the composition of mixing for the purpose of the surface tension reduction of coated composition and imparting coatings flexibility.
(C) plasticizer can enumerate sucrose fatty ester, fatty acid glyceride, mono-fatty acid glyceride, polyoxyethylene sorbitan fat
The surfactants such as fat acid esters；The polyalcohols such as glycerine, 1,3 butylene glycol, propane diols, polyethylene glycol；Glucose, HFCS, sugarcane
The sugar such as sugar；The sugar alcohols such as D-sorbite, maltitol, mannitol, antierythrite, xylitol；Dodecanol, tridecanol, ten
Four alkanols, pentadecanol, hexadecanol, heptadecanol, octadecanol, hexadecanol, isooctadecanol, 2- octyldodecanols etc.
The higher alcohol of (suitable is carbon number 6~22)；The greases such as medium chain fatty acid ester (suitable is carbon number 6~12).It
Can be used alone with one kind or appropriately combined two or more used.Wherein, it is excellent from from the aspect of the plasticization effect of coating membrane
Select glycerine.
Relative to coated composition entirety, combined amount preferably 0.3~5 mass %, more preferably 0.5~3 matter of (C) component
Amount %.By making combined amount more than the lower limit of above range, film when can more suppress to be coated comes off, by above-mentioned model
Below the upper limit enclosed, viscosity when can suppress to be coated while Cotton seeds become easier to, can obtain good enteric
Property.
The scope of the mass ratio preferably 0.05~3.0 represented with (C)/(B), more preferably 0.1~2.0, further preferably
0.15~1.5, particularly preferred 0.15~1.1.By making mass ratio more than the lower limit of above range, the epithelium performance under acidifying
It is higher, by the way that below the upper limit, coating property is more preferable.
Also the epithelium forming component (D) beyond (B) composition can be mixed in coated composition of the invention.(D) epithelium is formed
It is fine that composition can enumerate gelatin, pectin, curdlan, pulullan polysaccharide, Arabic gum, xanthans, gellan gum, hydroxypropyl methyl
Dimension element, sodium carboxymethylcellulose, hydroxypropyl cellulose, agar, shitosan, tamarind gum, locust bean gum, polyvinyl alcohol, ethyl
Cellulose aqueous dispersions etc..They can be used alone a kind of or appropriately combined two or more use.Wherein, from be coated property and
With (B) into from the point of view of subassembly, gelatin, pectin, curdlan, pulullan polysaccharide, Arabic gum, xanthan are preferably selected from
The composition of glue, gellan gum, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose and hydroxypropyl cellulose.
(D) combined amount of composition, relative to coated composition entirety, preferably 0.1~7 mass %, more preferably 0.2~5 matter
Amount %, further preferred 0.3~3 mass %.By making combined amount more than the lower limit of above range, can preferably obtain mixed
The effect of (D) composition is closed, if it exceeds above range is mixed, it is likely that influence is produced on enteric solubility.
Now, with (B)：(D) mass ratio preferably 1 that ((B)/(D)) is represented：3~1：0.05 (0.33~20), more preferably 1：
1~1：0.1 (1~10), further preferred 1：0.8~1：0.2 (1.25~5).By that, can obtain keeping within the range
On the basis of coating property and appearance looks elegant, dissolution particularly under acidity can rejection enteric excellent performance higher
Tablet.
(F) particulate can also be mixed in coated composition.By hybrid fine particles, tablet during due to Cotton seeds can be prevented
Between be attached to each other caused by coating membrane come off.(F) composition can enumerate talcum powder, calcium stearate, silica, titanium oxide
Deng can be used alone a kind of or appropriately combined two or more use.The particle diameter of particulate be 0.01~50 μm, preferably 0.1~
20μm.Additionally, identical with the occasion of lower floor's composition, the measure of particle diameter uses laser diffraction formula particle size distribution device
(dry type measure) is carried out.
(F) 0.05~7 overall mass % of the combined amount of composition, preferably coated composition, more preferably 0.1~5 matter
Amount %, further preferred 0.3~3 mass %.By making combined amount more than the lower limit of above range, can preferably obtain mixed
Close and state the effect of (F) composition, if it exceeds above range is mixed, it is likely that influence is produced on enteric solubility.
In addition, preferably not comprising bivalent metal ions such as copper ion, barium ions, calcium ions in coated composition.Because extra large
Alginates are crosslinked and gelation by these ions, and coating property is deteriorated.That is, making monovalence alginate with divalence sun
Ionic reaction is so that in the case of its crosslinking, although dry film is water-insoluble, but due to becoming viscosity because of gelation
Obtain too high, therefore the spraying of fine liquid and the ductility on tablet become difficult.As a result, it is difficult to uniform epithelium is formed, outward
See and be deteriorated, in addition, stripping property is unstable sometimes.Relative to 1 mole of the monomer of alginate, the permission of bivalent metal ion
Preferably less than 0.5 mole, more preferably less than 0.25 mole, further preferred less than 0.1 mole of scope.
In coated composition of the invention, in addition to mentioned component, can also be used alone a kind of or mix two in right amount
Usually used composition in the coated composition of the kind above.Defoamer, colouring agent etc. can be enumerated as such any condition.
Defoamer can for example enumerate fatty acid glyceride, dimethyl polysiloxane, dimethyl polysiloxane silica
Mixture, aqueous silicon dioxide, silica etc., can be used alone a kind of or appropriately combined two or more use.
Colouring agent can enumerate such as catechutannic acid powder, turmeric extract solution, Yellow ferric oxide, mandarin orange orange Essence, brown
Color iron oxide, carbon black, caramel, famille rose, carrotene liquid, beta carotene, licorice, goldleaf, black iron oxide, lightweight
Silicic acid anhydride, titanium oxide, di-iron trioxide, edible blue No. 1, edible yellow 4, No. 4 aluminum lakes of edible yellow, edible yellow 5
Number, edible Amaranth, edible red No. 3, edible red No. 102, NaOH, chlorophyll copper sodium, copper chlorophyll, barley it is green
Leaf extract, medical charcoal, Riboflavine Tertrabutyrate, riboflavin, green tea powder, Riboflavine sodium phosphate etc..
Coated composition of the invention can contain the organic solvents such as water, ethanol.Relative to whole coated composition, it is coated
Solvent combined amount in composition is suitable selected in the range of 1~98 mass %, preferably 50~98 mass %, more preferably 70~
96 mass %.
The thickness of above-mentioned enteric coatings is not particularly limited, preferably 5~1,000 μm, more preferably 10~500 μm.This
Outward, under the occasion of tablet, the adhesion amount of enteric coatings relative to plain piece 300mg preferably 1.5~60mg/300mg (0.5~
20 mass %), more preferably 3~45mg/300mg (1~15 mass %).Under granule, powder, the occasion of powder, preferably 10~
60 mass %, more preferably 15~50 mass %.By making the thickness of enteric coatings and adhesion amount in the lower limit of above range
More than, can obtain dissolution under acidity can the excellent preparation of rejection.On the other hand, by making enteric coatings
Adhesion amount can be controlled in appropriate manufacturing time below the upper limit of above range.
Additionally, the thickness of above-mentioned lower floor is not particularly limited with the thickness relationship of enteric coatings, as long as it is upper
State suitably in the range of.
The method for forming above-mentioned enteric coatings is not particularly limited, can be using known method.Can for example enumerate,
By to form lower floor be coated thing spray specific Coating Solution and heat drying and make to be coated the surface membranization of thing
Method.Coating Solution can be heated suitably, preferably 30~80 DEG C of temperature, preferably 40~80 DEG C of drying temperature.Relative to drying
Air quantity 1m3/ min, the adding speed preferably 1~5g/min of Coating Solution.This is coated into thing alternatively, it is also possible to use to be impregnated into
Dry dip-coating method after in Coating Solution.It is preferred that by the amount of moisture drying in coated preparation to 0.1~20 mass %, it is especially excellent
Choosing is dried to 0.5~5 mass %.
Now, seed-coating machine is not particularly limited, it is possible to use pan coater, fluidized-bed coating machine, drum type coating machine
Deng.
Additionally, not damaging in the range of effect of the invention, between above-mentioned lower floor and above-mentioned coatings, can also be formed
Appropriate intermediate layer.In the present invention, for example, can form shellac coating membrane, hydrogenated oil and fat coating membrane.
(IV) outermost layer
In the present invention, can be formed in the outside of above-mentioned enteric coatings using above-mentioned (D) epithelium forming component as needed
Outermost layer.Outward appearance, mouthfeel, taste can be changed by this.(D) epithelium forming component can enumerate gelatin, pectin, curdlan,
Pulullan polysaccharide, Arabic gum, xanthans, gellan gum, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, hydroxypropyl are fine
Dimension element, agar, shitosan, tamarind gum, locust bean gum, polyvinyl alcohol, aqueous ethylcellulose dispersion liquid etc..They can be independent
Using a kind of or appropriately combined two or more use.Wherein, consider from coating property angle, be preferably selected from gelatin, pectin, can obtain so
Glue, pulullan polysaccharide, Arabic gum, xanthans, gellan gum, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose and hydroxyl
The composition of propyl cellulose.
Above-mentioned outermost thickness is not particularly limited, preferably 1~200 μm, more preferably 2~100 μm.Additionally, tablet
Under occasion, relative to plain piece 300mg, outermost adhesion amount preferably 0.6~10.5mg/300mg (0.2~3.5 mass %), more
It is preferred that 1.5~7.5mg/300mg (0.5~2.5 mass %).Under granule, powder, the occasion of powder, preferably 1~30 matter
Amount %, more preferably 2~25 mass %.By making outermost thickness and adhesion amount more than the lower limit of above range, Ke Yigai
Become mouthfeel and taste.On the other hand, by making outermost thickness and adhesion amount below the upper limit of above range, can be suitable
Ground control manufacturing time.
In above-mentioned outermost layer composition, do not damaging in the range of effect of the invention, can have containing water, ethanol etc.
Machine solvent.Solvent combined amount in outermost layer composition, relative to outermost layer composition entirety, 1~98 mass %'s
In the range of properly select, preferably 50~98 mass %, more preferably 70~96 mass %.
The above-mentioned outermost method of formation is not particularly limited, can be using known method.Can for example enumerate, formed
Being coated on thing of lower floor and enteric coatings spray specific Coating Solution and heat drying and this is coated thing
The method of surface membranization.Coating Solution can be heated suitably, preferably 30~80 DEG C of temperature, preferably 40~80 DEG C of drying temperature.Phase
For drying air quantity 1m3/ min, the adding speed preferably 1~5g/min of Coating Solution.Alternatively, it is also possible to using thing will be coated
It is impregnated into rear dry dip-coating method in Coating Solution.It is preferred that by the amount of moisture drying in coated preparation to 0.1~20 mass %,
Particularly preferably dry to 0.5~5 mass %.
Now, seed-coating machine is not particularly limited, it is possible to use pan coater, fluidized-bed coating machine, drum type coating machine
Deng.
(V) manufacture method of coated preparation
Coated preparation of the invention can be manufactured via following operations, be sprayed containing (A) 6 mass % water by being coated thing
The solution of macromolecular compound of viscosity of the solution at 25 DEG C less than 300mPas and operation that is dry and forming lower floor；It is right
Solution and operation dry and that form enteric coatings of the outside spraying of the lower floor containing (B) alginate with (C) plasticizer；
As needed, by spraying containing (D) epithelium forming component solution and dry form outermost operation.Each operation it is detailed
Feelings as described above, but the mixing of Coating Solution that is used and coating conditions etc. do not damage can in the range of effect of the invention
Suitably to set, it is not particularly limited.
The Coating Solution of outermost each layer for above-mentioned lower floor, enteric coatings can be formed, forming as needed, can be with
Obtained by mixing above-mentioned essential component.So as to, using above-mentioned each Coating Solution be coated on thing formed in order lower floor,
Enteric coatings, outermost layer as needed, by this, it is possible to obtain having both good enteric solubility with excellent preservation stabilization
The coated preparation of property.Additionally, the Coating Solution of each layer is using water as solvent, so form respectively water-solubility membrane.
The enteric coatings formed by above-mentioned coated composition, containing above-mentioned (B) composition, but as described above by alginic acid
Saline solution convection drying forms water miscible film.The water miscible film has following characteristics：Under acidity, monovalent cation with
Hydrogen ion is replaced, and is become alginic acid and is formed insoluble film, is further dissolved under neutral~alkalescence.
The enteric coatings that above-mentioned coated composition is formed, with enteric solubility, i.e., with " do not dissolved in stomach and
Dissolving in enteron aisle, can make to be coated thing reach enteron aisle " property.Obtain the enteric coatings preparation that coating membrane is enteric solubility.
Further, the lower floor containing above-mentioned (A) composition is formd under enteric coatings, the lower floor has as guarantor
From the basic function of deterioration, therefore process over time can also as much as possible suppress acid to shield enteric coatings
Property under stripping property reduction, significantly improve the storage stability of coated preparation.
Additionally, further forming the outermost containing (D) composition as desired by the outside of above-mentioned enteric coatings
Layer, can bring change to taste, mouthfeel, outward appearance.
【Embodiment】
Hereinafter, provide embodiment and comparative example illustrates the present invention, but the present invention is not restricted to following embodiments.Separately
Outward, in following examples unless otherwise instructed, " % " of composition represents quality %, and ratio represents mass ratio.
Embodiment 1~15, comparative example 1,2
First, when preparing coated preparation, following plain piece is prepared.
[plain piece]
Mix following raw materials, carrying out compressing tablet using tablet press machine forms tablet (300mg, Φ 9.0mm, thickness 5mm).
<Plain piece is constituted>
Lactoferrin：1,156g
Piper longum extract powder：500g
Lactose：492.5g
Microcrystalline cellulose：731.5g
Sodium carboxymethylcellulose：60g
Sucrose fatty ester：30g
Silicon dioxide microparticle：30g
That Details as Follows is described for above-mentioned each composition.
Lactoferrin：Gloomy dairy industry forever (strain) system
Piper longum extract powder：Ball is apt to pharmacy (strain) system, " ヒ Ha Star エ キ ス end MF "
Lactose：Freund industries (strain) system, " lactose グ ラ ニ ュ ー "
Microcrystalline cellulose：Asahi Chemical Industry's chemistry (strain) system, " セ オ ラ ス FD-101 "
Sodium carboxymethylcellulose：Day Phosphorus chemical industry (strain) systems, " ECC-FA "
Sucrose fatty ester：Mitsubishi Chemical's food (strain) system, " リ ョ ー ト ー シ ュ ガ-エ ス テ Le S-370F "
Silicon dioxide microparticle：DSL Japan (strain) systems, " カ ー プ レ ッ Network ス FPS-500 "
Then by composition shown in following orders preparation table 2 below~4 for forming lower floor, enteric coatings and outermost
The Coating Solution of layer.
[preparation of lower floor's Coating Solution]
At room temperature respectively by (A) composition and (E) composition uniform dissolution in water.
[preparation of enteric coatings Coating Solution]
After being respectively dispersed in water (B) composition and (C) composition heating makes its uniform dissolution, the solution of mixed dissolution, adds
Plus other compositions are further mixed.
[preparation of outermost layer Coating Solution]
At room temperature by (D) composition uniform dissolution in water.
On the surface of above-mentioned made plain piece, lower floor, intestines are formed in order using above-mentioned prepared each Coating Solution
Dissolubility coatings and outermost layer as needed, prepare coated preparation (tablet).Condition when being coated to each layer is as follows.
[coating]
Condition difference when being coated lower floor, enteric coatings and outermost layer is as follows.
(lower floor)
Using seed-coating machine (POWREX (パ ウ レ ッ Network) makes, POWREX COATER-PRC-05), with Coating Solution 50g with average
2ml/min sprays to plain piece 200g, implements to be coated at about 50 DEG C of product temperature.2 points are dried after spraying at about 45 DEG C
Clock, obtains coated preparation (tablet).The thickness of coating membrane is in the range of 5~50 μm.
(enteric coatings)
Using seed-coating machine (POWREX systems, POWREX COATER-PRC-05), with Coating Solution (embodiment and comparative example 1：
150g, comparative example 2：Plain piece 200g is sprayed with average 2ml/min 204g), implements to be coated at about 50 DEG C of product temperature.
Dried 2 minutes at about 45 DEG C after spraying, obtain coated preparation (tablet).The thickness of coating membrane is in the range of 20~200 μm.
(outermost layer)
Using seed-coating machine (POWREX systems, POWREX COATER-PRC-05), with Coating Solution 50g with average 2g/min to plain piece
200g is sprayed, and implements to be coated at about 50 DEG C of product temperature.Dried 2 minutes at about 45 DEG C after spraying, obtain being coated system
Agent (tablet).The thickness of coating membrane is in the range of 5~50 μm.
To the coated preparation of above-mentioned gained, after being just coated according to following sequence evaluatings respectively and 50 DEG C, 75%RH
Under the conditions of take care of 4 months after enteric solubility, confirm to preserve steady by comparing evaluation result of both enteric solubilities before and after preservation
It is qualitative.Additionally, the outward appearance (coating) of preparation is evaluated after to being just coated.
[experiment of acid pH stripping property]
Using the liquid of Japanese Pharmacopoeia 1 (pH 1.2), dissolution test is carried out according to Japanese Pharmacopoeia ordinary test method (paddle method)..
◎：The stripping property of 2 hours is less than 10%
○：The stripping property of 2 hours is more than 10% and less than 20%
△：The stripping property of 2 hours is more than 20% and less than 40%
×：The stripping property of 2 hours is more than 40%
[neutrality~alkaline pH stripping property experiment]
Using the liquid of Japanese Pharmacopoeia 2 (pH6.8), dissolution test is carried out according to Japanese Pharmacopoeia ordinary test method (paddle method).
○：The stripping property of 2 hours is more than 70%
△：The stripping property of 2 hours is more than 30% and less than 70%
×：The stripping property of 2 hours is less than 30%
In addition, be " △ " in above-mentioned [experiment of acid pH stripping property], "○" or " ◎ " and [neutrality~alkaline pH is molten above-mentioned
Going out property is tested] in be set to " enteric solubility " in the case of "○".
[ocular estimate]
Based on following metewands, outward appearance is evaluated on the surface of preparation (tablet) after visual observations are just coated.
◎：It is uniform to be coated, have not seen defect, come off, coating surface is glossy.
○：It is uniform to be coated, it is nearly no to defect, come off, but coating surface slightly out-of-flatness.
△：The defect of visible coating on a part of tablet.
×：The defect of visible coating or come off on almost all of tablet.
The raw material that is used in embodiment and comparative example notes at foot.Additionally, the details of the alginate of (B) composition
Separately it is displayed in Table 1.
(lower floor)
Hydroxypropyl methyl cellulose：SHIN-ETSU HANTOTAI's chemical industry (strain) system, " メ ト ロ ー ズ SE-06 "
Pectin：Big Japanese pharmaceutical (strain) system, " Network ラ シ ッ Network AF701 "
Polyvinyl alcohol：Japan's synthesis chemical (strain) system, " Port リ PVC ニ Le ア ル コ ー Le EG-22P "
Arabic gum：Japanese powder pharmaceutical (strain) system, " ア ラ PVC ア ガ system "
Hydroxypropyl cellulose：Hydroxypropyl cellulose：Japanese Cao reaches (strain) system, " HPC-SSL "
Pulullan polysaccharide：The former system of (strain) woods, " プ Le ラ Application "
Sucrose：Big Japan Mingzhi's sugaring (strain) system, " sucrose "
(enteric coatings)
Glycerine：Slope this pharmaceutical industries (strain) system, " グ リ セ リ Application (food additives) "
Silica (silicon dioxide microparticle)：Fuji's chemistry of silicones (strain) system, " サ イ ロ ペ ー ジ 720 "
Talcum powder：Loose village's industry (strain) system, " グ ラ ウ Application タ Le Network PP "
(outermost layer)
Hydroxypropyl methyl cellulose：SHIN-ETSU HANTOTAI's chemical industry (strain) system, " メ ト ロ ー ズ SE-06 "
【Table 1】
【Table 2】
【Table 3】
【Table 4】
Claims (9)
1. a kind of coated preparation, it is characterised in that the coated preparation has：
Be coated thing, being coated the lower floor and the enteric coatings that are formed on the lower floor that are formed on thing,
Macromolecular compound of viscosity of (A) the 6 mass % aqueous solution at 25 DEG C less than 300mPas is contained in the lower floor,
The enteric coatings contain (B) alginate and (C) plasticizer.
2. coated preparation according to claim 1, (A) composition is selected from by hydroxypropyl methyl cellulose, pectin, can obtain
The group of right glue, pulullan polysaccharide, hydroxypropyl cellulose, polyvinyl alcohol and Arabic gum composition.
3. coated preparation according to claim 2, (A) composition is hydroxypropyl methyl cellulose.
4. the coated preparation according to any one of claims 1 to 3, (B) composition is (B-1) 1 mass % aqueous solution 20
DEG C when viscosity for more than 50mPas alginate.
5. coated preparation according to claim 4, wherein, also further containing (B-2) the 1 mass % aqueous solution at 20 DEG C
Viscosity less than 50mPas alginate.
6. the coated preparation according to any one of Claims 1 to 5, it further has in the outside of enteric coatings
Outermost layer, the outermost layer comprising (D) be selected from by gelatin, pectin, curdlan, pulullan polysaccharide, Arabic gum, xanthans,
Macromolecule chemical combination in the group of gellan gum, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose and hydroxypropyl cellulose composition
Thing.
7. coated preparation according to claim 6, (D) composition is hydroxypropyl methyl cellulose.
8. a kind of manufacture method of coated preparation, it is characterised in that the method includes following operations：
To being coated viscosity macromolecule chemical combination less than 300mPas of the thing spraying containing (A) the 6 mass % aqueous solution at 25 DEG C
The solution of thing and operation that is dry and forming lower floor, and
Solution containing (B) alginate and (C) plasticizer is sprayed to the outside of the lower floor and is dried and is formed enteric coatings
The operation of layer.
9. the manufacture method of coated preparation according to claim 8,
Wherein, further comprise, the outside spraying to the enteric coatings is molten containing following (D) macromolecular compounds
Liquid is simultaneously dried and forms outermost operation,
(D) macromolecular compound be selected from by gelatin, pectin, curdlan, pulullan polysaccharide, Arabic gum, xanthans,
Macromolecule chemical combination in the group of gellan gum, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose and hydroxypropyl cellulose composition
Thing.
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| JP2014-178935 | 2014-09-03 | ||
| JP2014178935 | 2014-09-03 | ||
| PCT/JP2015/074731 WO2016035756A1 (en) | 2014-09-03 | 2015-08-31 | Coated preparation and method for producing same |
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| JP (2) | JP6642438B2 (en) |
| KR (1) | KR102392313B1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108740371A (en) * | 2018-04-04 | 2018-11-06 | 广州智特奇生物科技股份有限公司 | Enteric capsulating material, using coated zinc oxide of the capsulating material and preparation method thereof |
| CN110997005A (en) * | 2017-08-09 | 2020-04-10 | 狮王株式会社 | Coating composition, coating film, coated preparation and process for producing the same |
| CN114585379A (en) * | 2019-11-08 | 2022-06-03 | 狮王株式会社 | Enteric coated preparation containing lactoferrin |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6780412B2 (en) * | 2016-09-28 | 2020-11-04 | ライオン株式会社 | Coating composition and coating formulation and method for manufacturing the same |
| JP7046323B2 (en) * | 2017-09-13 | 2022-04-04 | アリメント工業株式会社 | Multi-layer coating formulation |
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Also Published As
| Publication number | Publication date |
|---|---|
| TWI710376B (en) | 2020-11-21 |
| JPWO2016035756A1 (en) | 2017-06-15 |
| JP6911900B2 (en) | 2021-07-28 |
| WO2016035756A1 (en) | 2016-03-10 |
| JP2020011994A (en) | 2020-01-23 |
| KR102392313B1 (en) | 2022-05-02 |
| CN106794253B (en) | 2021-02-12 |
| KR20170049502A (en) | 2017-05-10 |
| JP6642438B2 (en) | 2020-02-05 |
| TW201625308A (en) | 2016-07-16 |
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