JP6783664B2 - Tablets high in glucosamine and chondroitin sulfate and their manufacturing methods - Google Patents
Tablets high in glucosamine and chondroitin sulfate and their manufacturing methods Download PDFInfo
- Publication number
- JP6783664B2 JP6783664B2 JP2016564912A JP2016564912A JP6783664B2 JP 6783664 B2 JP6783664 B2 JP 6783664B2 JP 2016564912 A JP2016564912 A JP 2016564912A JP 2016564912 A JP2016564912 A JP 2016564912A JP 6783664 B2 JP6783664 B2 JP 6783664B2
- Authority
- JP
- Japan
- Prior art keywords
- salt
- glucosamine
- chondroitin sulfate
- solution
- granules
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 title claims description 122
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 title claims description 122
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 title claims description 86
- 229920001287 Chondroitin sulfate Polymers 0.000 title claims description 86
- 229940059329 chondroitin sulfate Drugs 0.000 title claims description 86
- 238000004519 manufacturing process Methods 0.000 title claims description 46
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- 150000003839 salts Chemical class 0.000 claims description 175
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- 239000008187 granular material Substances 0.000 claims description 91
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 21
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- 239000001506 calcium phosphate Substances 0.000 description 9
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- PFPQMWRASYNLMZ-LGIMBNBCSA-N 2-(3,4-dihydroxyphenyl)-3-[(2s,3r,4r,5s,6r)-3,4-dihydroxy-5-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[[(2r,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxy-5,7-dihydroxychromen-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 PFPQMWRASYNLMZ-LGIMBNBCSA-N 0.000 description 6
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- 229960000292 pectin Drugs 0.000 description 1
- RFWLACFDYFIVMC-UHFFFAOYSA-D pentacalcium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O RFWLACFDYFIVMC-UHFFFAOYSA-D 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Chemical class OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 235000008729 phenylalanine Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000007065 protein hydrolysis Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- OVSQVDMCBVZWGM-QSOFNFLRSA-N quercetin 3-O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-QSOFNFLRSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 235000014102 seafood Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 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
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 150000008494 α-glucosides Chemical class 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、打錠性および流動性が向上したグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒および組成物、ならびにグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を高含有する錠剤およびそれらの製造方法に関する。 The present invention relates to granules and compositions containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof having improved tableting property and fluidity, and tablets and tablets containing a high content of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof. Regarding the manufacturing method.
グルコサミンは、動物体内では、軟骨や結合組織などにムコ多糖の構成成分として広く分布している単分子のアミノ糖で、具体的にはグルコースの2位の水酸基がアミノ基に置換した2-アミノグルコースである。また、カニやエビなどの甲殻類のキチンにも多く含まれている。
グルコサミンは、軟骨細胞により生産され、軟骨成分の生成を促進する。従って、グルコサミンは変形性関節症等の関節炎に有効とされ、栄養補給用サプリメントとして市販されている。Glucosamine is a single-molecule amino sugar that is widely distributed in cartilage and connective tissue as a constituent of mucopolysaccharide in the animal body. Specifically, 2-amino in which the hydroxyl group at the 2-position of glucose is replaced with an amino group. Glucose. It is also abundant in crustacean chitin such as crabs and shrimp.
Glucosamine is produced by chondrocytes and promotes the production of cartilage components. Therefore, glucosamine is effective for arthritis such as osteoarthritis and is commercially available as a nutritional supplement.
しかし、グルコサミンおよびその塩の結晶粉末は流動性が悪く、打錠機の臼への均一な充填が悪くなり、キャッピング、ラミネーション等の打錠障害の発生頻度が高まったり、錠剤の重量にバラツキが生じたりする等の問題があった。
一方、グルコサミンまたはその塩の結晶末を粉砕物とすることで、結着性の高い粉砕品を取得し、当該結着性の高い結晶と結着性の低い結晶末との両方を使用することで、タブレット用組成物の流動性を向上させ、打錠障害の発生頻度を低く抑えることができる(特許文献1)。しかし、該グルコサミン結晶粉砕物含有組成物は、流動性が実用上不十分である。However, the crystal powder of glucosamine and its salt has poor fluidity, the uniform filling of the tablet mortar into the mortar becomes poor, the frequency of tableting disorders such as capping and lamination increases, and the weight of the tablet varies. There was a problem such as occurring.
On the other hand, by pulverizing the crystal powder of glucosamine or a salt thereof, a pulverized product having high binding property is obtained, and both the crystal having high binding property and the crystal powder having low binding property are used. Therefore, the fluidity of the composition for tablets can be improved, and the frequency of occurrence of tableting disorders can be suppressed low (Patent Document 1). However, the fluidity of the glucosamine crystal pulverized product-containing composition is practically insufficient.
また、グルコサミンに、グルコサミン以外の、デンプン、多糖類、単糖などの糖類を含有する溶液を噴霧した後、又は噴霧しつつ、造粒加工することによって、打錠加工に適した物性を有するグルコサミン顆粒が得られる (特許文献2)。
一方、コンドロイチン硫酸は、関節炎等に効果があり、コンドロイチン硫酸を含有する医薬品が市販されている。また、コンドロイチン硫酸、およびグルコサミンを含有し、人や動物の結合組織の治療用組成物が報告されている (特許文献3)。グルコサミンおよびコンドロイチン硫酸の投与による結合組織の治療に対する相乗効果が知られている。In addition, glucosamine has physical properties suitable for tableting by spraying a solution containing saccharides other than glucosamine, such as starch, polysaccharide, and monosaccharide, on glucosamine, or by granulating while spraying. Granules are obtained (Patent Document 2).
On the other hand, chondroitin sulfate is effective for arthritis and the like, and pharmaceutical products containing chondroitin sulfate are commercially available. In addition, a composition for treating connective tissue of humans and animals containing chondroitin sulfate and glucosamine has been reported (Patent Document 3). The synergistic effect of administration of glucosamine and chondroitin sulfate on the treatment of connective tissue is known.
しかし、市販のグルコサミンサプリメントの多くは、グルコサミンの打錠性向上のために賦形剤を含有しており、そのためコンドロイチン硫酸およびグルコサミンの含量は低くならざるを得ない。
スプレードライで得られた顆粒を打錠に用いている例として、ナプロキセンまたはナプロキセンナトリウム、崩壊剤、結合剤からなる混合スラリーをスプレードライすることで、球状および多孔性でかつ流動性に優れたサイズの均一な粒子を与えること、および高度に圧縮可能であることが報告されている (特許文献4)。However, many commercially available glucosamine supplements contain excipients to improve the tableting properties of glucosamine, which inevitably lowers the content of chondroitin sulfate and glucosamine.
As an example of using the granules obtained by spray-drying for tableting, by spray-drying a mixed slurry consisting of naproxen or naproxen sodium, a disintegrant, and a binder, the size is spherical, porous, and has excellent fluidity. It has been reported that it provides uniform particles of and is highly compressible (Patent Document 4).
一方、スプレードライを用いて顆粒を製造することにより、打錠性および流動性が向上したグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒および組成物が得られること、ならびにそれら顆粒または組成物を用いることによりグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を高含有する錠剤が得られることは知られていない。 On the other hand, by producing granules using spray-drying, granules and compositions containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof having improved tableting properties and fluidity can be obtained, and the granules or compositions thereof. It is not known that tablets having a high content of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof can be obtained by using the product.
本発明の目的は、打錠性および流動性が向上したグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒および組成物、ならびにグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を高含有する錠剤およびそれらの製造方法を提供することにある。 An object of the present invention is granules and compositions containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof having improved tableting property and fluidity, and tablets and a tablet containing a high content of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof. The purpose is to provide a method for producing them.
本発明は以下の（１）〜（１９）に関する。
（１）グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する溶液または懸濁液（以下当該溶液または懸濁液を溶液1と略す）をスプレードライして得られるグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒。
（２）溶液1が、さらにコラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物を含有する溶液または懸濁液（以下当該溶液または懸濁液を溶液2と略す）である（１）に記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒。
（３）溶液2に含有される化合物が、コラーゲンまたはその酵素処理物およびルチンまたはその酵素処理物からなる群から選ばれる1つ以上の化合物である（２）に記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒。
（４）グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒に対するグルコサミンまたはその塩の含有量が60〜95重量%である（１）〜（３）のいずれかに記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒。
（５）グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒に対するコンドロイチン硫酸またはその塩の含有量が3〜20重量%である（１）〜（４）のいずれかに記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒。
（６）グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒に対するコラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物の合計含有量が0.1〜10重量%である（２）〜（５）のいずれかに記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒。
（７）（１）〜（６）のいずれかに記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒に、滑沢剤、流動性改善剤および添加物からなる群より選ばれる1つ以上の化合物を添加して得られる組成物。
（８）（１）〜（７）のいずれかに記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒または組成物を打錠して得られる錠剤。
（９）錠剤に対する錠剤中のグルコサミンまたはその塩の含有量が60〜95重量%である（８）に記載の錠剤。
（１０）錠剤に対する錠剤中のコンドロイチン硫酸またはその塩の含有量が3〜20重量%である（８）または（９）に記載の錠剤。
（１１）錠剤に対する錠剤中のコラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物の合計含有量が0.1〜10重量%である（８）〜（１０）のいずれかに記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する錠剤。
（１２）溶液1または2をスプレードライする工程を含むグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒の製造方法。
（１３）溶液1または2をスプレードライする工程ならびに該工程で得られるグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒に滑沢剤、流動性改善剤および添加物からなる群より選ばれる1つ以上の化合物を添加する工程を含むグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する組成物の製造方法。
（１４）溶液1または2に含まれるグルコサミンまたはその塩の含有量が15〜27重量％である（１２）または（１３）に記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒または組成物の製造方法。
（１５）溶液1または2に含まれるコンドロイチン硫酸またはその塩の含有量が、1〜6重量％である（１２）〜（１４）のいずれかに記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒または組成物の製造方法。
（１６）溶液1または溶液2をスプレードライする工程ならびに該工程で得られるグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒を用いて打錠する工程を含むグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する錠剤の製造方法。
（１７）溶液1または溶液2をスプレードライする工程、該工程で得られるグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒に滑沢剤、流動性改善剤および添加物からなる群より選ばれる1つ以上の化合物を添加し混合する工程ならびに該工程で得られるグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する組成物を打錠する工程を含むグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する錠剤の製造方法。
（１８）溶液1または2に含まれるグルコサミンまたはその塩の含有量が15〜27重量％である（１６）または（１７）に記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する錠剤の製造方法。
（１９）溶液1または2に含まれるコンドロイチン硫酸またはその塩の含有量が1〜6重量％である（１６）〜（１８）のいずれかに記載のグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する錠剤の製造方法。The present invention relates to the following (1) to (19).
(1) Glucosamine or a salt thereof and chondroitin sulfate or a solution or suspension containing the salt thereof (hereinafter, the solution or suspension is abbreviated as Solution 1) is spray-dried to obtain glucosamine or a salt thereof and chondroitin sulfate or Granules containing the salt.
(2) A solution or suspension in which solution 1 further contains one or more compounds selected from the group consisting of collagen or an enzyme-treated product thereof, rutin or an enzyme-treated product thereof, thiamine, riboflavin, pyridoxin, niacin and pantothenic acid. Granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof according to (1), which is a solution (hereinafter, the solution or suspension is abbreviated as solution 2).
(3) Glucosamine or a salt thereof and chondroitin according to (2), wherein the compound contained in the solution 2 is one or more compounds selected from the group consisting of collagen or an enzyme-treated product thereof and rutin or an enzyme-treated product thereof. Granules containing sulfuric acid or a salt thereof.
(4) The glucosamine or a salt thereof according to any one of (1) to (3), wherein the content of glucosamine or a salt thereof is 60 to 95% by weight based on the granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof. And granules containing chondroitin sulfate or a salt thereof.
(5) The glucosamine or its salt according to any one of (1) to (4), wherein the content of chondroitin sulfate or its salt is 3 to 20% by weight with respect to the granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof. Granules containing salts and chondroitin sulfate or salts thereof.
(6) One selected from the group consisting of collagen or an enzyme-treated product thereof for granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, rutin or an enzyme-treated product thereof, thiamine, riboflavin, pyridoxin, niacin and pantothenic acid. Granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof according to any one of (2) to (5), wherein the total content of the above compounds is 0.1 to 10% by weight.
(7) Granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof according to any one of (1) to (6) are selected from the group consisting of a lubricant, a fluidity improver and an additive 1 A composition obtained by adding one or more compounds.
(8) A tablet obtained by tableting granules or compositions containing glucosamine or a salt thereof according to any one of (1) to (7) and chondroitin sulfate or a salt thereof.
(9) The tablet according to (8), wherein the content of glucosamine or a salt thereof in the tablet with respect to the tablet is 60 to 95% by weight.
(10) The tablet according to (8) or (9), wherein the content of chondroitin sulfate or a salt thereof in the tablet with respect to the tablet is 3 to 20% by weight.
(11) The total content of one or more compounds selected from the group consisting of collagen or an enzyme-treated product thereof, rutin or an enzyme-treated product thereof, thiamine, riboflavin, pyridoxin, niacin and pantothenic acid in a tablet is 0.1 to 1. A tablet containing 10% by weight of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof according to any one of (8) to (10).
(12) A method for producing granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, which comprises a step of spray-drying solution 1 or 2.
(13) The step of spray-drying the solution 1 or 2 and the granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt obtained in the step are selected from the group consisting of a lubricant, a fluidity improver and an additive. A method for producing a composition containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, which comprises a step of adding one or more compounds.
(14) The granules or granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof according to (12) or (13), wherein the content of glucosamine or a salt thereof contained in solution 1 or 2 is 15 to 27% by weight. Method for producing the composition.
(15) The glucosamine or salt thereof and chondroitin sulfate or salt thereof according to any one of (12) to (14), wherein the content of chondroitin sulfate or a salt thereof contained in solution 1 or 2 is 1 to 6% by weight. A method for producing granules or compositions containing.
(16) Glucosamine or a salt thereof and chondroitin sulfate or a step of spray-drying solution 1 or 2 and tableting with granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof obtained in the step. A method for producing a tablet containing the salt.
(17) A step of spray-drying solution 1 or solution 2, selected from the group consisting of a lubricant, a fluidity improver and an additive in the granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof obtained in the step. Glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, which comprises a step of adding and mixing one or more compounds thereof and a step of tableting a composition containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof obtained in the step. A method for producing a tablet containing.
(18) The tablet containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof according to (16) or (17), wherein the content of glucosamine or a salt thereof contained in solution 1 or 2 is 15 to 27% by weight. Production method.
(19) The glucosamine or salt thereof and chondroitin sulfate or salt thereof according to any one of (16) to (18), wherein the content of chondroitin sulfate or a salt thereof contained in solution 1 or 2 is 1 to 6% by weight. Method for producing the contained tablet.
本発明により、打錠性および流動性が向上したグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒および組成物、ならびにグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を高含有する錠剤およびそれらの製造方法を提供することができる。 According to the present invention, granules and compositions containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof having improved tableting property and fluidity, and tablets containing a high content of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof and theirs. A manufacturing method can be provided.
以下、本発明を詳細に説明する。
本発明で用いられるグルコサミンは、例えば、発酵生産する方法、エビ・カニから抽出する方法等により取得することができる。また、グルコサミンは、各社の市販品を購入することにより入手することもできる。
グルコサミンを発酵生産する方法としては、例えば、植物を原料として微生物発酵により製造する方法等が挙げられ、好ましくは、Metabolic Engineering. 7 (3), 2005, 201-214に記載の方法が挙げられる。Hereinafter, the present invention will be described in detail.
Glucosamine used in the present invention can be obtained, for example, by a method of fermenting production, a method of extracting from shrimp or crab, or the like. Glucosamine can also be obtained by purchasing commercially available products from each company.
Examples of the method for fermenting and producing glucosamine include a method for producing glucosamine by microbial fermentation using a plant as a raw material, and preferably, the method described in Metabolic Engineering. 7 (3), 2005, 201-214.
グルコサミンをエビ・カニから抽出する方法としては、例えば、エビやカニの殻を原料としてキチンを抽出し、これを加水分解後、精製し、乾燥して調製する方法等が挙げられ、好ましくは特開2004-359908、US3683076等に記載の方法が挙げられる。
市販されているグルコサミンとしては、例えば、発酵グルコサミンK（協和発酵バイオ社製）、グルコサミンFM（協和発酵バイオ社製）を挙げられる。Examples of the method for extracting glucosamine from shrimp and crab include a method in which chitin is extracted from shrimp and crab shells as a raw material, hydrolyzed, purified, and dried to prepare. The methods described in Kai 2004-359908, US3683076, etc. can be mentioned.
Examples of commercially available glucosamine include fermented glucosamine K (manufactured by Kyowa Hakko Bio Co., Ltd.) and glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.).
本発明で用いるグルコサミンまたはその塩は、市販のグルコサミンまたはその塩でもよいし、またはキチンの加水分解および精製により得られるグルコサミン等をそのまま用いる、上記製造法後に乾燥工程を省略した未乾燥のグルコサミンまたはその塩を用いる、もしくは、グルコサミンまたはその塩を粉砕して用いる方法でもよい。グルコサミンまたはその塩の粉砕方法は、外力による圧縮、衝撃またはせん断や、粒子自身の慣性力による衝突または摩擦のいずれの原理を用いてもよく、例えば、ボールミル、ローラーミル、高速回転ミル、ジェットミル等を用いる粉砕方法等が挙げられる。 The glucosamine or a salt thereof used in the present invention may be a commercially available glucosamine or a salt thereof, or undried glucosamine or a salt thereof which omits the drying step after the above production method and uses glucosamine or the like obtained by hydrolysis and purification of chitin as it is. The salt may be used, or glucosamine or a salt thereof may be pulverized and used. The pulverization method of glucosamine or a salt thereof may use any principle of compression by an external force, impact or shear, collision or friction by the inertial force of the particles themselves, for example, a ball mill, a roller mill, a high-speed rotary mill, or a jet mill. And the like using a crushing method or the like.
ボールミルとしては、例えば、転動ボールミル、遊星ミル等が挙げられ、ローラーミルとしては、例えば、堅式ローラーミル、ロールクラッシャー、高圧ロールプレス等が挙げられ、高速回転ミルとしては、例えば、ハンマーミル、ピンミル、ケージミル等が挙げられる。
本発明におけるコンドロイチン硫酸またはその塩は、例えば、化学的に合成する方法、または抽出する方法等により取得することができる。また、コンドロイチン硫酸は、各社の市販品を購入することにより入手することもできる。Examples of the ball mill include a rolling ball mill, a planetary mill and the like, examples of the roller mill include a rigid roller mill, a roll crusher, a high pressure roll press and the like, and examples of the high speed rotating mill include a hammer mill. , Pin mill, cage mill and the like.
The chondroitin sulfate or a salt thereof in the present invention can be obtained by, for example, a method of chemically synthesizing or a method of extracting. In addition, chondroitin sulfate can also be obtained by purchasing commercially available products of each company.
コンドロイチン硫酸を化学的に合成する方法としては、例えば特開2003-199583に記載の方法等が挙げられる。
コンドロイチン硫酸を抽出する方法としては、例えば特開2014-009164に記載の方法等が挙げられる。
該抽出する方法等により取得することができるコンドロイチン硫酸は、どのような生物に由来するものでもよく、例えば、エイやサメ、ウシ、クジラ、ウサギ、ヒツジ、カブトガニ、ブタ、イカ等の動物を挙げることができる。Examples of the method for chemically synthesizing chondroitin sulfate include the methods described in JP-A-2003-199583.
Examples of the method for extracting chondroitin sulfate include the methods described in JP-A-2014-009164.
The chondroitin sulfate that can be obtained by the extraction method or the like may be derived from any organism, and examples thereof include animals such as rays, sharks, cows, whales, rabbits, sheep, horseshoe crabs, pigs, and squids. be able to.
コンドロイチン硫酸の市販品としては、例えば、サメ軟骨、サメヒレ軟骨等の原料から抽出して粉末化したコンドロイチン硫酸を含有するサメ軟骨抽出粉末等が挙げられ、例えばマリンカーティリッジ40S（焼津水産化学工業社製）、SCP(NB)（マルハニチロ社製）、サメ軟骨食品用コンドロイチンHG-40 (日本薬品社製)等が挙げられる。
グルコサミンの塩およびコンドロイチンの塩としては、それぞれ同一または異なって、酸付加塩、金属塩、アンモニウム塩、有機アミン付加塩、アミノ酸付加塩等があげられる。Examples of commercially available products of chondroitin sulfate include shark cartilage extract powder containing chondroitin sulfate extracted and powdered from raw materials such as shark cartilage and shark fin cartilage. For example, Marinker Tillage 40S (Yakitsu Fisheries Chemical Industry Co., Ltd.) ), SCP (NB) (manufactured by Maruhanichiro), chondroitin HG-40 for shark cartilage food (manufactured by Nippon Yakuhin Co., Ltd.), etc.
Examples of the glucosamine salt and the chondroitin salt include acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts and the like, which are the same or different from each other.
酸付加塩としては、例えば、塩酸塩、硫酸塩、硝酸塩、リン酸塩等の無機酸塩、酢酸塩、マレイン酸塩、フマル酸塩、クエン酸塩、リンゴ酸塩、乳酸塩、α−ケトグルタル酸塩、グルコン酸塩、カプリル酸塩等の有機酸塩等があげられる。
金属塩としては、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩、マグネシウム塩、カルシウム塩等のアルカリ土類金属塩、アルミニウム塩、亜鉛塩等があげられる。Examples of the acid addition salt include inorganic acid salts such as hydrochloride, sulfate, nitrate and phosphate, acetate, maleate, fumarate, citrate, malate, lactate and α-ketoglutar. Examples thereof include organic acid salts such as acid salts, gluconates and caprylates.
Examples of the metal salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt, zinc salt and the like.
アンモニウム塩としては、例えば、アンモニウム、テトラメチルアンモニウム等の塩があげられる。
有機アミン付加塩としては、例えば、モルホリン、ピペリジン等の塩があげられる。 アミノ酸付加塩としては、例えば、グリシン、フェニルアラニン、リジン、アスパラギン酸、グルタミン酸等の塩があげられる。Examples of the ammonium salt include salts such as ammonium and tetramethylammonium.
Examples of the organic amine addition salt include salts such as morpholine and piperidine. Examples of the amino acid addition salt include salts of glycine, phenylalanine, lysine, aspartic acid, glutamic acid and the like.
本発明におけるグルコサミンとグルコサミンの塩を比較すると、グルコサミンの塩の方が、熱に安定で褐変し難いこと、および経口摂取した後、腸管から吸収され易いため好ましく、グルコサミン塩酸塩の使用がより好ましい。
１．本発明の顆粒、組成物および錠剤
本発明の顆粒は、打錠性および流動性が向上したグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒であり、より具体的にはグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する溶液をスプレードライすることにより得られる顆粒である。さらに、グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩に加え、コラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、コラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物を含有する溶液、好ましくはグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩に加えられる化合物が、コラーゲンまたはその酵素処理物およびルチンまたはその酵素処理物からなる群から選ばれる1つ以上の化合物である溶液をスプレードライすることにより得られる顆粒もまた、本発明の顆粒である。Comparing the salts of glucosamine and glucosamine in the present invention, the salt of glucosamine is preferable because it is stable to heat and does not easily turn brown, and it is easily absorbed from the intestinal tract after oral ingestion, and the use of glucosamine hydrochloride is more preferable. ..
1. 1. Granules, Compositions and Tablets of the Present Invention The granules of the present invention are granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof having improved tableting property and fluidity, and more specifically, glucosamine or a salt thereof. And granules obtained by spray-drying a solution containing chondroitin sulfate or a salt thereof. Furthermore, in addition to glucosamine or its salt and chondroitin sulfate or its salt, collagen or its enzyme-treated product, rutin or its enzyme-treated product, collagen or its enzyme-treated product, rutin or its enzyme-treated product, thiamine, riboflavin, pyridoxin, niacin. And a solution containing one or more compounds selected from the group consisting of pantothenic acid, preferably glucosamine or a salt thereof and a compound added to chondroitin sulfate or a salt thereof are collagen or an enzyme-treated product thereof and rutin or an enzyme-treated product thereof. The granules obtained by spray-drying a solution of one or more compounds selected from the group consisting of are also the granules of the present invention.
コラーゲンまたはその酵素処理物は、豚、牛、鶏等の家畜由来、魚介類由来のもの等、動物由来のものであればいずれでもよい。また、コラーゲンとしては、例えば、水溶性コラーゲンペプチドSS、HPフィッシュコラーゲン（以上、協和発酵バイオ社製）等、市販のものを用いてもよい。
ルチンまたはその酵素処理物における、ルチンの酵素処理物は、ルチンおよびルチン類縁体を酵素処理によって配糖体化したものであり、該ルチン類縁体としては、例えば、ケルセチン、イソクエルシトリン、モリン、ミリシトリン、ミリセチン等が挙げられ、酵素処理物または酵素処理における該酵素としては、例えば、α-グルコシル糖転移酵素等が挙げられる。The collagen or its enzyme-treated product may be any animal-derived product such as that derived from livestock such as pigs, cows and chickens, and that derived from seafood. Further, as the collagen, commercially available collagen such as water-soluble collagen peptide SS and HP fish collagen (all manufactured by Kyowa Hakko Bio Co., Ltd.) may be used.
In the enzyme-treated product of rutin or its enzyme-treated product, the enzyme-treated product of rutin is a glycosylated product of rutin and rutin-related bodies by enzyme treatment, and the rutin-related products include, for example, quercetin, isoquercitrin, morin, Examples thereof include myricitrin, mylicetin and the like, and examples of the enzyme-treated product or the enzyme in the enzyme treatment include α-glucosyl glycosyltransferase.
α-グルコシル糖転移酵素はα-グルコシドを加水分解し、生じた糖をそのまま別のアグリコンに付加させる酵素を表す。
ルチンの酵素処理物は、同様の配合組成を有する組成物であれば、その由来については特に制限はないが、例えば、エンジュ、ソバ等の抽出物を糖転移酵素で処理する方法等によって得ることができる。具体的には特開平7-10898、特開2003-33164等に記載の方法で得ることができる。The α-glucosyltransferase represents an enzyme that hydrolyzes α-glucoside and adds the resulting sugar to another aglycone as it is.
The enzyme-treated rutin is not particularly limited in its origin as long as it is a composition having the same composition, but it can be obtained by, for example, a method of treating an extract such as Enju or buckwheat with a glycosyltransferase. Can be done. Specifically, it can be obtained by the methods described in JP-A-7-10898, JP-A-2003-33164 and the like.
チアミンは、ビタミンB1とも呼ばれる水溶性ビタミンで、糖質および分岐鎖脂肪酸の代謝に用いられるものを表す。
リボフラビンは、ビタミンB2、ラクトフラビンとも呼ばれる水溶性ビタミンで、脂肪、炭水化物およびタンパク質の代謝や呼吸に用いられるものを表す。
ピリドキシンとはビタミンB6に分類される化合物のひとつである水溶性ビタミンで、赤血球生産の促進等の機能を持つものを表す。Thiamine is a water-soluble vitamin, also called vitamin B1, which is used for the metabolism of sugars and branched-chain fatty acids.
Riboflavin is a water-soluble vitamin, also called vitamin B2 or lactoflavin, which is used for metabolism and respiration of fats, carbohydrates and proteins.
Pyridoxine is a water-soluble vitamin that is one of the compounds classified as vitamin B6 and has a function of promoting erythrocyte production.
ナイアシンとはニコチン酸とニコチン酸アミドの総称でビタミンB3とも呼ばれる水溶性ビタミンであり、循環系、消化系、神経系の働きを促進する等の機能をもつものを表す。
上記リボフラビン、ピリドキシン、ナイアシンおよびチアミンは、各化合物の塩であってもよく、塩としては、それぞれ、同一または異なって、塩酸塩、硫酸塩、硝酸塩、セシル硫酸塩等が挙げられ、塩酸塩が好ましい。Niacin is a water-soluble vitamin that is also called vitamin B3, which is a general term for nicotinic acid and nicotinamide, and represents those having functions such as promoting the functions of the circulatory system, digestive system, and nervous system.
The above-mentioned riboflavin, pyridoxin, niacin and thiamine may be salts of each compound, and examples of the salts include hydrochlorides, sulfates, nitrates, cecil sulfates and the like, which are the same or different from each other. preferable.
パントテン酸は、D(+)-N-(2,4-ジヒドロキシ-3,3-ジメチルブチリル)-β-アラニンであり、ビタミンB群に含まれる水溶性ビタミンで、CoA（補酵素A）の構成成分として、糖代謝や脂肪酸代謝に関わる物質のことを表す。パントテン酸は、塩であってもよく、塩としては例えば、カルシウム塩、ナトリウム塩等が挙げられ、カルシウム塩が好ましい。
上記チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸は、蛋白質加水分解法、化学合成法、酵素法又は発酵法など、いずれの製造方法で製造されたものでもよいし、市販品を用いることもできる。Pantothenic acid is D (+)-N- (2,4-dihydroxy-3,3-dimethylbutyryl) -β-alanine, a water-soluble vitamin contained in the B vitamins, and CoA (coenzyme A). Represents substances involved in glucose metabolism and fatty acid metabolism as constituents of. Pantothenic acid may be a salt, and examples of the salt include a calcium salt and a sodium salt, and a calcium salt is preferable.
The thiamine, riboflavin, pyridoxine, niacin and pantothenic acid may be produced by any production method such as a protein hydrolysis method, a chemical synthesis method, an enzyme method or a fermentation method, or a commercially available product may be used.
本発明の組成物は、打錠性および流動性が向上したグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する組成物であり、より具体的には本発明の顆粒に滑沢剤、流動性改善剤、および添加物からなる群より選ばれる1つ以上の化合物を添加して得られる組成物である。
滑沢剤としては、食品等に使用できるものであれば特に制限されないが、例えば、ステアリン酸、ステアリン酸マグネシウム、ステアリン酸カルシウム、ショ糖脂肪酸エステル、グリセリン脂肪酸エステル、硬化油脂、微粒二酸化ケイ素等が挙げられる。滑沢剤は、錠剤の表面のみにあっても、錠剤内部に分散していてもよい。本発明の錠剤中で滑沢剤が占める割合は、合計で0.5〜12重量％が好ましく、1〜10重量％がより好ましい。また、2種類以上の滑沢剤を用いても良い。The composition of the present invention is a composition containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof having improved tableting property and fluidity, and more specifically, the granules of the present invention have a lubricant and fluidity. A composition obtained by adding one or more compounds selected from the group consisting of an improving agent and an additive.
The lubricant is not particularly limited as long as it can be used in foods and the like, and examples thereof include stearic acid, magnesium stearate, calcium stearate, sucrose fatty acid ester, glycerin fatty acid ester, hardened fat and oil, and fine silicon dioxide. Be done. The lubricant may be only on the surface of the tablet or dispersed inside the tablet. The proportion of the lubricant in the tablets of the present invention is preferably 0.5 to 12% by weight in total, more preferably 1 to 10% by weight. Moreover, you may use two or more kinds of lubricants.
流動性改善剤としては、食品等に使用できるものであれば特に制限されないが、例えば、第三リン酸カルシウム、リン酸水素カルシウム等があげられる。本発明の錠剤中で流動性改善剤が占める割合は、0.1〜7質量％が好ましく、0.5〜6質量％がより好ましい。
添加物としては、例えば、崩壊剤、糖類、甘味料、香料、酸味料、結合剤、抗酸化剤、着色剤等が挙げられ、コラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸も本発明の顆粒に添加する添加物として用いてもよい。The fluidity improving agent is not particularly limited as long as it can be used for foods and the like, and examples thereof include tricalcium phosphate and calcium hydrogen phosphate. The proportion of the fluidity improver in the tablet of the present invention is preferably 0.1 to 7% by mass, more preferably 0.5 to 6% by mass.
Examples of additives include disintegrants, sugars, sweeteners, flavors, acidulants, binders, antioxidants, colorants and the like, and collagen or its enzyme-treated product, rutin or its enzyme-treated product, thiamine, etc. Riboflavin, pyridoxin, niacin and pantothenic acid may also be used as additives to be added to the granules of the present invention.
崩壊剤としては、例えば、デンプン、寒天、ゼラチン末、結晶セルロース、炭酸カルシウム、炭酸水素ナトリウム、クエン酸カルシウム、デキストラン、ペクチン、低置換度ヒドロキシプロピルセルロース、クロスカルメロースナトリウム、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、カルボキシメチルセルロースカルシウム、カルボキシメチルスターチナトリウム、低置換度カルボキシメチルスターチナトリウム、クロスポビドン等が挙げられる。 Examples of the disintegrant include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, calcium citrate, dextran, pectin, low-substituted hydroxypropyl cellulose, croscarmellose sodium, carboxymethyl cellulose, and sodium carboxymethyl cellulose. , Carboxymethyl cellulose calcium, sodium carboxymethyl starch, low-substituted carboxymethyl starch sodium, crospovidone and the like.
糖類としては、食品等に使用できるものであれば特に制限されないが、例えば、単糖類、二糖類、糖アルコール、オリゴ糖等があげられ、好ましくは糖アルコールがあげられる。
単糖類としては、例えば、グルコース、キシロース、ガラクトース、フラクトース等が挙げられる。二糖類としては、例えば、トレハロース、蔗糖、乳糖、パラチノース等が挙げられる。糖アルコールとしては、例えばマルチトール、エリスリトール、ソルビトール、キシリトール等が挙げられる。オリゴ糖としては、例えばラフィノース、イヌロオリゴ糖 (チコリオリゴ糖)、パラチノースオリゴ糖等が挙げられる。本発明の錠剤中で糖類が占める割合は、製剤における一般的な使用の量の範囲内であれば特に限定されない。The saccharide is not particularly limited as long as it can be used for foods and the like, and examples thereof include monosaccharides, disaccharides, sugar alcohols, oligosaccharides and the like, and sugar alcohols are preferable.
Examples of monosaccharides include glucose, xylose, galactose, fructose and the like. Examples of the disaccharide include trehalose, sucrose, lactose, palatinose and the like. Examples of sugar alcohols include maltitol, erythritol, sorbitol, xylitol and the like. Examples of oligosaccharides include raffinose, inuro-oligosaccharide (ticoli-oligosaccharide), palatinose oligosaccharide and the like. The proportion of saccharides in the tablets of the present invention is not particularly limited as long as it is within the range of the amount generally used in the preparation.
甘味料としては、食品等に使用できるものであれば特に制限されないが、例えば、サッカリンナトリウム、グリチルリチン二カリウム、アスパルテーム、ステビア、ソーマチン等が挙げられる。本発明の錠剤中で甘味剤が占める割合は、製剤における一般的な使用の量の範囲内であれば特に限定されない。
香料としては、食品に使用できるものであれば特に制限されないが、例えばレモンフレーバー、レモンライムフレーバー、グレープフルーツフレーバー、アップルフレーバー等が挙げられる。本発明の錠剤中で香料が占める割合は、製剤における一般的な使用の量の範囲内であれば特に限定されない。The sweetener is not particularly limited as long as it can be used in foods and the like, and examples thereof include sodium saccharin, dipotassium glycyrrhizin, aspartame, stevia, and thaumatin. The proportion of the sweetener in the tablet of the present invention is not particularly limited as long as it is within the range of the amount generally used in the preparation.
The flavor is not particularly limited as long as it can be used in foods, and examples thereof include lemon flavor, lemon lime flavor, grapefruit flavor, apple flavor and the like. The proportion of the fragrance in the tablet of the present invention is not particularly limited as long as it is within the range of the amount generally used in the preparation.
酸味料としては、食品等に使用できるものであれば特に制限されないが、例えば、クエン酸、酒石酸、リンゴ酸等があげられる。本発明の錠剤中で酸味料が占める割合は、製剤における一般的な使用の量の範囲内であれば特に限定されない。
結合剤としては、食品等に使用できるものであれば特に制限されないが、例えば、ゼラチン、プルラン等があげられる。本発明の錠剤中で結合剤が占める割合は、製剤における一般的な使用の量の範囲内であれば特に限定されない。The acidulant is not particularly limited as long as it can be used in foods and the like, and examples thereof include citric acid, tartaric acid, malic acid and the like. The proportion of the acidulant in the tablet of the present invention is not particularly limited as long as it is within the range of the amount generally used in the preparation.
The binder is not particularly limited as long as it can be used for foods and the like, and examples thereof include gelatin and pullulan. The proportion of the binder in the tablets of the present invention is not particularly limited as long as it is within the range of the amount generally used in the preparation.
抗酸化剤としては、食品等に使用できるものであれば特に制限されないが、例えば、トコフェロール、アスコルビン酸、塩酸システイン、L-アスコルビン酸ステアリン酸エステル等があげられる。本発明の錠剤中で抗酸化剤が占める割合は、製剤における一般的な使用の量の範囲内であれば特に限定されない。
着色剤としては、食品等に使用できるものであれば特に制限はされないが、例えば、食用黄色5号、食用赤色2号、食用青色2号、カロチノイド色素、トマト色素等があげられる。本発明の錠剤中で着色剤が占める割合は、製剤における一般的な使用の量の範囲内であれば特に限定されない。The antioxidant is not particularly limited as long as it can be used in foods and the like, and examples thereof include tocopherol, ascorbic acid, cysteine hydrochloride, and L-ascorbic acid stearic acid ester. The proportion of the antioxidant in the tablet of the present invention is not particularly limited as long as it is within the range of the amount generally used in the preparation.
The colorant is not particularly limited as long as it can be used for foods and the like, and examples thereof include edible yellow No. 5, edible red No. 2, edible blue No. 2, carotenoid pigment, tomato pigment and the like. The proportion of the colorant in the tablet of the present invention is not particularly limited as long as it is within the range of the amount generally used in the preparation.
本発明の錠剤は、グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を高含有する錠剤であり、具体的には本発明の顆粒または組成物を打錠することにより得られる錠剤である。
２．本発明の顆粒の製造方法
本発明における顆粒は以下の工程i-1)、i-2)またはi-3)およびii)で製造することができる。
i-1) グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を溶媒中で加熱・撹拌混合を行うことでそれらを溶解または懸濁させ溶液1を得る。
i-2) グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩に、コラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物を加えて溶媒中で加熱・撹拌混合を行うことでそれらを溶解または懸濁させ溶液2を得る。
i-3) グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩に、コラーゲンまたはその酵素処理物、およびルチンまたはその酵素処理物からなる群から選ばれる1つ以上の化合物を加えて溶媒中で加熱・撹拌混合を行うことで溶解または懸濁させ溶液2を得る。およびii) i-1)、i-2)またはi-3)で得られる溶液1または2をスプレードライして顆粒を得る。The tablet of the present invention is a tablet having a high content of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, and specifically, a tablet obtained by tableting the granules or compositions of the present invention.
2. Method for Producing Granules of the Present Invention The granules of the present invention can be produced by the following steps i-1), i-2) or i-3) and ii).
i-1) Glucosamine or a salt thereof and chondroitin sulfate or a salt thereof are heated and stirred in a solvent to dissolve or suspend them to obtain Solution 1.
i-2) One or more selected from the group consisting of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, collagen or an enzyme-treated product thereof, rutin or an enzyme-treated product thereof, thiamine, riboflavin, pyridoxin, niacin and pantothenic acid. Compounds are added and heated and stirred and mixed in a solvent to dissolve or suspend them to obtain Solution 2.
i-3) Add one or more compounds selected from the group consisting of collagen or its enzyme-treated product, and rutin or its enzyme-treated product to glucosamine or its salt and chondroitin sulfate or its salt, and heat and stir in a solvent. The solution 2 is obtained by dissolving or suspending by mixing. And ii) spray dry the solution 1 or 2 obtained from i-1), i-2) or i-3) to obtain granules.
具体的には、本発明の顆粒は、以下の製造工程に従って製造することができる。
上記工程における溶液1とは、グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を室温から溶媒の沸点までの温度の溶媒に溶解または懸濁させたものを表し、溶媒としては、例えば水、アルコール等が挙げられ、水が好ましい。アルコールとしては、例えば、エタノール、グリセリン等が挙げられる。上記溶液中または懸濁液中の全溶質の含有量としては、1〜50重量%が挙げられ、5〜45重量%が好ましく、10〜40重量%がより好ましい。Specifically, the granules of the present invention can be produced according to the following production process.
The solution 1 in the above step represents a solution in which glucosamine or a salt thereof and chondroitin sulfate or a salt thereof are dissolved or suspended in a solvent having a temperature from room temperature to the boiling point of the solvent, and examples of the solvent include water, alcohol and the like. Water is preferred. Examples of the alcohol include ethanol, glycerin and the like. The content of the total solute in the solution or suspension includes 1 to 50% by weight, preferably 5 to 45% by weight, and more preferably 10 to 40% by weight.
上記工程における溶液2とは、グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩、ならびにコラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物、好ましくはコラーゲンまたはその酵素処理物およびルチンまたはその酵素処理物からなる群より選ばれる1つ以上の化合物を室温から溶媒の沸点までの温度の溶媒に溶解または懸濁させたものを表し、溶媒としては、例えば水、アルコール等が挙げられ、水が好ましい。アルコールとしては、例えば、エタノール、グリセリン等が挙げられる。上記溶液中または懸濁液中の全溶質の含有量としては、1〜50重量%が挙げられ、5〜45重量%が好ましく、10〜40重量%がより好ましい。 Solution 2 in the above step is selected from the group consisting of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, collagen or an enzyme-treated product thereof, rutin or an enzyme-treated product thereof, thiamine, riboflavin, pyridoxin, niacin and pantothenic acid. One or more compounds, preferably one or more compounds selected from the group consisting of collagen or an enzyme-treated product thereof and rutin or an enzyme-treated product thereof, were dissolved or suspended in a solvent having a temperature from room temperature to the boiling point of the solvent. Examples of the solvent include water, alcohol and the like, and water is preferable. Examples of the alcohol include ethanol, glycerin and the like. The content of the total solute in the solution or suspension includes 1 to 50% by weight, preferably 5 to 45% by weight, and more preferably 10 to 40% by weight.
懸濁液は均一または不均一のどちらでもよく、均一が望ましい。また、溶質が溶媒に一部溶解していてもよく、さらに懸濁液はコロイド溶液でもかまわない。
溶液1または2におけるグルコサミンまたはその塩の含有量は、溶液1または2に対して15〜27重量％が好ましく、18〜24重量％がより好ましい。
溶液1または2におけるコンドロイチン硫酸またはその塩の含有量は、溶液1または2に対して1〜6重量％が好ましく、1.8〜4.0重量％がより好ましい。The suspension may be uniform or non-uniform, preferably uniform. Further, the solute may be partially dissolved in a solvent, and the suspension may be a colloidal solution.
The content of glucosamine or a salt thereof in Solution 1 or 2 is preferably 15 to 27% by weight, more preferably 18 to 24% by weight, based on Solution 1 or 2.
The content of chondroitin sulfate or a salt thereof in Solution 1 or 2 is preferably 1 to 6% by weight, more preferably 1.8 to 4.0% by weight, based on Solution 1 or 2.
溶液2におけるコラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物の合計含有量は、溶液2に対して0.2〜2重量％が好ましく、0.5〜1.5重量％がより好ましい。
懸濁液中の全溶質の含有量（一部が溶解している場合は、溶解している溶質および溶解していない溶質を合わせて溶質とする）としては、35〜65重量％が挙げられ、40〜60重量％が好ましい。 スプレードライは液状形態の化合物または混合物から顆粒を得るために一般に用いられ、当該方法で得られる顆粒は、液状の組成物が熱風中に数100 μm以下の微小な粒子として噴霧され、乾燥されながら塔内を落下していくことで粉末として回収されるため、得られた粉末は、球形に近く流動性に優れ、水溶性が高いという性質を有している。The total content of one or more compounds selected from the group consisting of collagen or its enzyme-treated product, rutin or its enzyme-treated product, thiamine, riboflavin, pyridoxine, niacin and pantothenic acid in Solution 2 is 0.2 with respect to Solution 2. It is preferably ~ 2% by weight, more preferably 0.5 ~ 1.5% by weight.
The content of the total solute in the suspension (when a part is dissolved, the dissolved solute and the undissolved solute are combined to form a solute) is 35 to 65% by weight. , 40-60% by weight is preferred. Spray drying is commonly used to obtain granules from a compound or mixture in liquid form, and the granules obtained by this method are such that the liquid composition is sprayed into hot air as fine particles of several hundred μm or less and dried. Since it is recovered as powder by falling in the tower, the obtained powder has the properties of being close to a sphere, having excellent fluidity, and being highly water-soluble.
また、スプレードライに用いられる素材は一時的に熱風に曝されるが、曝されている時間が非常に短いことと水の蒸発潜熱のためあまり温度が上がらないことから、素材の熱変性が起きにくく、復水による変化も小さい。さらに、非常に熱に弱い素材の場合、熱風の代わりに冷風を供給することも可能である。その場合、乾燥能力は落ちるが、よりマイルドな乾燥を実現できる点で好ましい。 In addition, the material used for spray drying is temporarily exposed to hot air, but the material is thermally denatured because the exposure time is very short and the temperature does not rise so much due to the latent heat of vaporization of water. It is difficult and the change due to condensate is small. Furthermore, in the case of a material that is extremely sensitive to heat, it is possible to supply cold air instead of hot air. In that case, although the drying ability is reduced, it is preferable in that a milder drying can be achieved.
上記工程ii)におけるスプレードライとは、液状形態のものから粉末を得るために一般に用いられる方法であり、液状の組成物が熱風中に数100 μm以下の微小な粒子として噴霧され、乾燥されながら塔内を落下していくことで粉末として回収される。スプレードライに用いられる素材は一時的に熱風に曝されるが、曝されている時間が非常に短いことと水の蒸発潜熱のためあまり温度が上がらないことから、素材の熱変性が起きにくく、復水による変化も小さいものである。また、非常に熱に弱い素材の場合、熱風の代わりに冷風を供給する場合も可能である。その場合、乾燥能力は落ちるが、よりマイルドな乾燥を実現できる点で好ましい。 The spray drying in the above step ii) is a method generally used to obtain a powder from a liquid form, in which the liquid composition is sprayed into hot air as fine particles of several hundred μm or less and dried. It is collected as powder by falling inside the tower. The material used for spray drying is temporarily exposed to hot air, but since the exposure time is very short and the temperature does not rise so much due to the latent heat of vaporization of water, thermal denaturation of the material is unlikely to occur. The change due to condensate is also small. Further, in the case of a material that is extremely sensitive to heat, it is possible to supply cold air instead of hot air. In that case, although the drying ability is reduced, it is preferable in that a milder drying can be achieved.
次いでスプレードライヤーを用いて、送風温度150〜200 ℃および排風温度55〜85 ℃の条件にて、溶液または懸濁液のスプレードライを行うことで本発明の製造方法に用いる顆粒を得ることができる。
上記工程ii)でスプレードライをする際には、溶液を用いる方が好ましい。
スプレードライヤーの噴霧方式としては、例えば、ノズル式、ディスク式等が挙げられ、ノズル式としては、例えば、Pulvis Mini-Spray GB22 (ヤマト科学社製) 等が挙げられ、ディスク式としては、例えばL8-i型スプレードライヤー (大川原化工機社製) 等が挙げられる。Next, the granules used in the production method of the present invention can be obtained by spray-drying the solution or suspension under the conditions of a blower temperature of 150 to 200 ° C. and an exhaust air temperature of 55 to 85 ° C. using a spray dryer. it can.
When spray-drying in the above step ii), it is preferable to use a solution.
Examples of the spraying method of the spray dryer include a nozzle type and a disk type, examples of the nozzle type include Pulvis Mini-Spray GB22 (manufactured by Yamato Scientific Co., Ltd.), and examples of the disk type are L8. -i type spray dryer (manufactured by Okawara Kakoki Co., Ltd.), etc. can be mentioned.
ノズル式の場合、ノズルの径としては0.1〜4.0 mmが好ましく、0.3〜3.5 mmがより好ましい。ノズルの噴出圧力としては10〜450 kg/cm2が好ましく、50〜300 kg/cm2がより好ましい。入り口温度としては100〜200 ℃が挙げられ、110〜195 ℃が好ましく、120〜190 ℃がより好ましい。出口温度としては40〜100 ℃が挙げられ、50〜90 ℃が好ましく、60〜80 ℃がより好ましい。In the case of the nozzle type, the diameter of the nozzle is preferably 0.1 to 4.0 mm, more preferably 0.3 to 3.5 mm. Preferably 10 to 450 kg / cm 2 as ejection pressure of the nozzle, more preferably 50~300 kg / cm 2. Examples of the inlet temperature include 100 to 200 ° C, preferably 110 to 195 ° C, and more preferably 120 to 190 ° C. The outlet temperature includes 40 to 100 ° C, preferably 50 to 90 ° C, and more preferably 60 to 80 ° C.
ディスク式の場合、アトマイザ回転数としては、20000〜45000 rpmが好ましく、25000〜40000 rpmがより好ましい。入り口温度としては100〜200 ℃が挙げられ、110〜195 ℃が好ましく、120〜190 ℃がより好ましい。出口温度としては40〜100 ℃が挙げられ、50〜90 ℃が好ましく、60〜80 ℃がより好ましい。
本発明の製造方法で得られる顆粒に含まれるグルコサミンまたはその塩の含有量としては、グルコサミンまたはその塩として、65〜99重量％であることが好ましく、70〜95重量％であることがより好ましく、75〜93重量％であることが特に好ましい。In the case of the disk type, the atomizer rotation speed is preferably 20000 to 45000 rpm, more preferably 25000 to 40000 rpm. Examples of the inlet temperature include 100 to 200 ° C, preferably 110 to 195 ° C, and more preferably 120 to 190 ° C. The outlet temperature includes 40 to 100 ° C, preferably 50 to 90 ° C, and more preferably 60 to 80 ° C.
The content of glucosamine or a salt thereof contained in the granules obtained by the production method of the present invention is preferably 65 to 99% by weight, more preferably 70 to 95% by weight, as glucosamine or a salt thereof. , 75-93% by weight is particularly preferred.
本発明の製造方法で得られる顆粒に含まれるコンドロイチン硫酸またはその塩の含有量としては、好ましくは3〜22重量%含有し、さらに好ましくは5〜16重量%含有する。
本発明の製造方法で得られる顆粒に含まれるコラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物の総含有量は、本発明の顆粒に対して0.1〜10重量％が好ましく、0.5〜5重量％がより好ましい。
３．本発明の組成物の製造方法
本発明の組成物は、以下の工程iii)で製造することができる。
iii) 上記工程ii)で得られる顆粒に、滑沢剤、流動性改善剤および添加物からなる群より選ばれる1つ以上の化合物を添加し、好ましくは混合する。The content of chondroitin sulfate or a salt thereof contained in the granules obtained by the production method of the present invention is preferably 3 to 22% by weight, more preferably 5 to 16% by weight.
Total content of one or more compounds selected from the group consisting of collagen or its enzyme-treated product, rutin or its enzyme-treated product, thiamine, riboflavin, pyridoxine, niacin and pantothenic acid contained in the granules obtained by the production method of the present invention. The amount is preferably 0.1 to 10% by weight, more preferably 0.5 to 5% by weight, based on the granules of the present invention.
3. 3. Method for Producing Composition of the Present Invention The composition of the present invention can be produced by the following step iii).
iii) To the granules obtained in the above step ii), one or more compounds selected from the group consisting of a lubricant, a fluidity improver and an additive are added and preferably mixed.
滑沢剤、流動性改善剤および添加物は、それぞれ独立した粉体の形態であってもよいし、予めこれらを組み合わせて、公知の湿式または乾式造粒方法等を用いて造粒した顆粒状の形態にして添加してもよい。
混合は、例えば、バスケットミル、V型混合機、フレットミル、タンブラー混合機等の混合機を用いて行われるか、またはポリエチレン袋内に、混合させる成分を加えて手で上下左右に振っても行うことができる。
４．整粒末の製造方法
本発明の顆粒または組成物には、上記方法で得られる顆粒または組成物を整粒して得られる整粒末も含まれ、該整粒末は以下の工程iv)で製造することができる。
iv) 上記工程ii)またはiii)で得られる顆粒または組成物を篩過して整粒末を得る。The lubricant, fluidity improver and additive may be in the form of independent powders, or they may be combined in advance to form granules granulated by a known wet or dry granulation method or the like. May be added in the form of.
Mixing is performed using, for example, a mixer such as a basket mill, a V-type mixer, a fret mill, or a tumbler mixer, or the components to be mixed are added to a polyethylene bag and shaken by hand up, down, left and right. It can be carried out.
4. Method for Producing Granule Powder The granule or composition of the present invention also includes granule powder obtained by sizing the granule or composition obtained by the above method, and the granule powder is obtained in the following step iv). Can be manufactured.
iv) The granules or compositions obtained in the above steps ii) or iii) are sieved to obtain a sized powder.
工程iv)の篩過としては、上記工程ii) またはiii)で得られた顆粒または組成物を篩に入れて、手で振動させて篩過する方法、または篩機を用いて顆粒または組成物を篩過する方法等が挙げられる。
工程iv)の篩過に用いられる機器としては、例えば、分級機・振動ふるい[湿式・乾式/網:カートリッジ式(標準)または内リング式(標準)]（ダルトン社製）、佐藤式振動ふるい機（晃栄産業社製）等が挙げられる。As the sieving in step iv), the granules or compositions obtained in the above steps ii) or iii) are placed in a sieve and shaken by hand for sieving, or the granules or compositions are sieved using a sieving machine. Examples include a method of sieving.
Equipment used for sieving in step iv) includes, for example, classifier / vibration sieve [wet / dry / net: cartridge type (standard) or inner ring type (standard)] (Dalton), Sato type vibration sieve. Machines (manufactured by Koei Sangyo Co., Ltd.) can be mentioned.
上記篩過の際に用いる篩いとしては特に限定されず、例えば4号篩(4750 μm)〜60号篩(250 μm)等が挙げられ、8号篩 (2360 μm)〜42号篩 (355 μm)が好ましく、12号篩 (1400 μm)〜32号篩 (500 μm)がより好ましい。
５．本発明の錠剤の製造方法
本発明の錠剤は以下の工程v)により製造することができる。
v) 上記ii)で得られる顆粒、またはiii)で得られる組成物、好ましくはiv)で得られる整粒末を打錠して錠剤を製造する。The sieve used for the above sieving is not particularly limited, and examples thereof include No. 4 sieve (4750 μm) to No. 60 sieve (250 μm), and No. 8 sieve (2360 μm) to No. 42 sieve (355 μm). ) Is preferable, and No. 12 sieve (1400 μm) to No. 32 sieve (500 μm) are more preferable.
5. Method for Producing Tablets of the Present Invention The tablets of the present invention can be produced by the following step v).
v) The granules obtained in ii) or the composition obtained in iii), preferably the sized powder obtained in iv) are tableted to produce tablets.
具体的には、本発明の錠剤は、以下の製造工程に従って製造することができる。
工程v)では、本発明の顆粒または組成物、好ましくは整粒末を打錠用粒として適当な方法により圧縮成形して錠剤を製造する。圧縮成形する方法としては、例えば、打錠用粒をそのまま圧縮成形する通例の方法や、あらかじめ滑沢剤を杵表面および臼壁に塗布してから、滑沢剤を含有しない打錠用粒を圧縮成形する、いわゆる外部滑沢圧縮成形方法等が挙げられる。Specifically, the tablet of the present invention can be produced according to the following production process.
In step v), the granules or compositions of the present invention, preferably the sized powder, are compression-molded as tablets for tableting by an appropriate method to produce tablets. As a method of compression molding, for example, a conventional method of compression molding the tableting granules as they are, or a tableting granules containing no lubricant after applying a lubricant to the surface of the punch and the mortar wall in advance. Examples thereof include a so-called external pestle compression molding method of compression molding.
圧縮成形時に用いる機器としては、例えば単発式圧縮成型機、ロータリー圧縮成形機、油圧プレス機等の圧縮機等を用いることができる。
本発明の製造方法で得られる錠剤に含まれるグルコサミンまたはその塩含有量としては、グルコサミンまたはその塩として、60〜95重量％であることが好ましく、65〜90重量％であることがより好ましく、70〜88重量％であることが特に好ましい。As the equipment used at the time of compression molding, for example, a compressor such as a single-shot compression molding machine, a rotary compression molding machine, or a hydraulic press can be used.
The content of glucosamine or a salt thereof contained in the tablet obtained by the production method of the present invention is preferably 60 to 95% by weight, more preferably 65 to 90% by weight, as glucosamine or a salt thereof. It is particularly preferably 70 to 88% by weight.
本発明の製造方法で得られる錠剤に含まれるコンドロイチン硫酸またはその塩の含有量としては、コンドロイチン硫酸またはその塩として、3〜20重量％が好ましく、5〜15重量％がより好ましい。
本発明の製造方法で得られる錠剤に含まれるコラーゲンまたはその酵素処理物、ルチンまたはその酵素処理物、チアミン、リボフラビン、ピリドキシン、ナイアシンおよびパントテン酸からなる群から選ばれる1つ以上の化合物の合計含有量は、0.1〜10重量%が好ましく、0.5〜5重量％がより好ましい。The content of chondroitin sulfate or a salt thereof contained in the tablets obtained by the production method of the present invention is preferably 3 to 20% by weight, more preferably 5 to 15% by weight, as chondroitin sulfate or a salt thereof.
The total content of one or more compounds selected from the group consisting of collagen or an enzyme-treated product thereof, rutin or an enzyme-treated product thereof, thiamine, riboflavin, pyridoxine, niacin and pantothenic acid contained in the tablets obtained by the production method of the present invention. The amount is preferably 0.1 to 10% by weight, more preferably 0.5 to 5% by weight.
本発明の製造方法により得られる錠剤は、錠剤中に、本発明の顆粒を、好ましくは80〜99重量％、さらに好ましくは85〜96重量％含む。
本発明の製造方法で得られる錠剤の形状は、特に制限されないが、例えば丸錠、三角錠、砲丸錠等が好ましい。本発明の錠剤の大きさは、特に制限されないが、例えば質量で0.1〜2 g、直径で0.3〜2.0 cmであるのが好ましい。The tablet obtained by the production method of the present invention contains the granules of the present invention in the tablet, preferably in an amount of 80 to 99% by weight, more preferably 85 to 96% by weight.
The shape of the tablet obtained by the production method of the present invention is not particularly limited, but for example, a round tablet, a triangular tablet, a shot put tablet and the like are preferable. The size of the tablet of the present invention is not particularly limited, but is preferably 0.1 to 2 g by mass and 0.3 to 2.0 cm in diameter, for example.
本発明の製造方法で得られる錠剤は、例えば、かけ、くずれ等が生じない硬度を有しているのが好ましい。錠剤の硬度は、一般的に錠剤硬度計で錠剤の直径方向の破壊強度として測定されるが、その値は3〜20 kgfであるのが好ましく、5〜18 kgfであるのがより好ましく、7〜16 kgfであるのが特に好ましい。
錠剤の硬度は、市販の錠剤破壊強度測定機、例えば、TH-203CP型(富山産業社製)等により測定できる。The tablets obtained by the production method of the present invention preferably have a hardness that does not cause, for example, sprinkling or breaking. The hardness of a tablet is generally measured by a tablet hardness tester as the breaking strength in the diameter direction of the tablet, but the value is preferably 3 to 20 kgf, more preferably 5 to 18 kgf, 7 It is particularly preferably ~ 16 kgf.
The hardness of the tablet can be measured by a commercially available tablet breaking strength measuring machine, for example, TH-203CP type (manufactured by Toyama Sangyo Co., Ltd.).
本発明の製造方法では、圧縮成形機の杵臼にあらかじめ極微量の滑沢剤を塗布し、滑沢剤が塗布された杵臼を有する圧縮成形機で滑沢剤を含有しない混合物を圧縮成形する、いわゆる外部滑沢圧縮成形方法を用いても打錠障害を生じることなく所望の硬度を有する錠剤を製造することができる。
上記打錠障害としては、例えば、スティッキング (杵に粉末が付着する現象)、バインディング (臼と錠剤の摩擦が大きくなる現象)、キャッピング (錠剤が帽子状に剥離する現象)、ラミネーション (錠剤が層状に剥離する現象) 等が挙げられる。In the production method of the present invention, a very small amount of lubricant is applied to the mill of the compression molding machine in advance, and a mixture containing no lubricant is compression-molded by a compression molding machine having a mill coated with the lubricant. Even if a so-called external smooth compression molding method is used, tablets having a desired hardness can be produced without causing tableting trouble.
The above-mentioned tableting disorders include, for example, sticking (a phenomenon in which powder adheres to a pestle), binding (a phenomenon in which the friction between a mortar and a tablet increases), capping (a phenomenon in which a tablet peels off like a hat), and lamination (a phenomenon in which tablets are layered). (Phenomenon of peeling) and so on.
本発明の製造方法で得られる錠剤は、さらに、防湿性、保存安定性等の向上のため、例えば糖、糖アルコール等によりコーティングされた糖衣錠又はコーティング錠であってもよい。
以下に、実施例に基づいて本発明をより詳細に説明するが、本発明はこれらに限定されるものではない。The tablets obtained by the production method of the present invention may be sugar-coated tablets or coated tablets coated with, for example, sugar, sugar alcohol, etc. in order to further improve moisture resistance, storage stability, and the like.
Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited thereto.
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 320 gおよびサメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 52 ｇを精製水1116 mLに溶解して25重量％の水溶液を得た。該水溶液を用いて、アトマイザ回転数35000 rpm、入り口温度180 ℃および出口温度70 ℃の条件に設定したスプレードライヤー [L8-i型スプレードライヤー (大川原化工機社製)] で、スプレードライして顆粒を250〜300ｇ得た。当該顆粒のうち186 gにショ糖脂肪酸エステル [DKエステルF20W (第一工業製薬社製)] 10 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 4 gを加えて、ポリエチレン袋内で充分に混合して組成物得て、これを16号篩 (1000 μm) を用いて篩過して整粒末を200 g得た。当該整粒末を単発式圧縮成型機 [竪型成形機6B-2M (菊水製作所社製)]を用いて、1000 kgfの打錠圧で圧縮成型を行って8.2 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。 Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 320 g and shark cartilage extract powder [Marinker Tillage 40S (manufactured by YAIZU SUISAN CHEMICAL INDUSTRIES)] 52 g dissolved in 1116 mL of purified water to 25% by weight An aqueous solution was obtained. Using the aqueous solution, spray dry the granules with a spray dryer [L8-i type spray dryer (manufactured by Okawara Kakoki Co., Ltd.)] set under the conditions of atomizer rotation speed 35000 rpm, inlet temperature 180 ° C and outlet temperature 70 ° C. Was obtained in an amount of 250 to 300 g. To 186 g of the granules, add 10 g of sucrose fatty acid ester [DK ester F20W (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.)] and 4 g of tri-calcium phosphate [tritric calcium phosphate (manufactured by Taihei Chemical Industry Co., Ltd.)] to a polyethylene bag. The composition was obtained by mixing thoroughly in the water, and this was sieved using a No. 16 sieve (1000 μm) to obtain 200 g of sized powder. The sizing powder is compression-molded with a single-shot compression molding machine [Vertical molding machine 6B-2M (manufactured by Kikusui Seisakusho)] at a tableting pressure of 1000 kgf, and each tablet shows a hardness of 8.2 kgf. Twenty 350 mg tablets were obtained.
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 320 ｇ、サメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 40 gおよびコラーゲン [水溶性フィッシュコラーゲン (協和発酵バイオ社製)] 12 gを精製水1116 mLに溶解して全溶質が25重量％の水溶液を得た。次に実施例1と同様の方法により顆粒、組成物および整粒末を得た後に、900 kgfの打錠圧で圧縮成形を行い、11.2 kgfの硬度を示す錠剤を20錠得た。 Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 320 g, shark cartilage extract powder [Marinker Tillage 40S (manufactured by Yakitsu Fisheries Chemical Industry Co., Ltd.)] 40 g and collagen [Water-soluble fish collagen (manufactured by Kyowa Hakko Bio Co., Ltd.) )] 12 g was dissolved in 1116 mL of purified water to obtain an aqueous solution having a total solute content of 25% by weight. Next, the granules, composition and sized powder were obtained by the same method as in Example 1, and then compression molding was performed with a tableting pressure of 900 kgf to obtain 20 tablets having a hardness of 11.2 kgf.
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 320 ｇ、サメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 40 gおよび酵素処理ルチン [αGルチンPS (東洋精糖社製)] 12 gを精製水1116 mLに溶解して全溶質が25重量％の水溶液を得た。該水溶液を用いて、実施例1と同様の方法により顆粒、組成物および整粒末を得た後に、1000 kgfの打錠圧で圧縮成形を行い、11.5 kgfの硬度を示す錠剤を20錠得た。 Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 320 g, shark cartilage extract powder [Marinker Tillage 40S (manufactured by Yakitsu Fisheries Chemical Industry Co., Ltd.)] 40 g and enzyme-treated rutin [αG rutin PS (manufactured by Toyo Purified Sugar Co., Ltd.) )] 12 g was dissolved in 1116 mL of purified water to obtain an aqueous solution having a total solute content of 25% by weight. Using the aqueous solution, granules, composition and sized powder were obtained by the same method as in Example 1, and then compression molding was performed with a tableting pressure of 1000 kgf to obtain 20 tablets having a hardness of 11.5 kgf. It was.
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 320ｇ、サメ軟骨抽出粉末[SCP(NB) (マルハニチロ社製)] 52 gを精製水1116 mLに溶解して25重量％の水溶液を得た。該水溶液を用いて、実施例1と同様の方法により顆粒、組成物および整粒末を得た後に、950 kgfの打錠圧で圧縮成形を行い、9.5 kgfの硬度を示す錠剤を20錠得た。 Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 320 g, shark cartilage extract powder [SCP (NB) (manufactured by Maruhanichiro)] 52 g was dissolved in 1116 mL of purified water to obtain a 25 wt% aqueous solution. .. Using the aqueous solution, granules, composition and sized powder were obtained by the same method as in Example 1, and then compression molding was performed with a tableting pressure of 950 kgf to obtain 20 tablets having a hardness of 9.5 kgf. It was.
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 340 ｇおよびサメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 32 gを精製水1116 mLに溶解して25重量％の水溶液を得た。該水溶液を用いて、実施例1と同様の方法により顆粒、組成物および整粒末を得た後に、1250 kgfの打錠圧で圧縮成形を行い、10.7 kgfの硬度を示す錠剤を20錠得た。 Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 340 g and shark cartilage extract powder [Marinker Tillage 40S (manufactured by YAIZU SUISAN CHEMICAL INDUSTRIES)] 32 g dissolved in 1116 mL of purified water to 25% by weight An aqueous solution was obtained. Using the aqueous solution, granules, composition and sized powder were obtained by the same method as in Example 1, and then compression molding was performed with a tableting pressure of 1250 kgf to obtain 20 tablets having a hardness of 10.7 kgf. It was.
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 320 ｇおよびサメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 40 gを精製水1080 mLに溶解して25重量％の水溶液を得た。該水溶液を用いて、実施例1と同様の方法により顆粒を250〜300 g得た。当該顆粒のうち180 gにコラーゲン [水溶性フィッシュコラーゲン (協和発酵バイオ社製)] 6 g、ショ糖脂肪酸エステル [DKエステルF20W (第一工業製薬社製)] 10 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 4 gを加えて、ポリエチレン袋内で充分に混合して組成物を得て、これを16号篩 (1000 μm) を用いて篩過して整粒末200 gを得た。当該整粒末を実施例1の方法により1000 kgfの打錠圧で圧縮成型を行った結果、10.5 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。 Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 320 g and shark cartilage extract powder [Marinker Tillage 40S (manufactured by YAIZU SUISAN CHEMICAL INDUSTRIES)] 40 g dissolved in 1080 mL of purified water to 25% by weight An aqueous solution was obtained. Using the aqueous solution, 250 to 300 g of granules were obtained by the same method as in Example 1. 180 g of the granules are collagen [water-soluble fish collagen (manufactured by Kyowa Hakko Bio Co., Ltd.)] 6 g, sucrose fatty acid ester [DK ester F20 W (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.)] 10 g and calcium phosphate tribasic [third Calcium phosphate (manufactured by Taihei Kagaku Sangyo Co., Ltd.)] 4 g is added and mixed thoroughly in a polyethylene bag to obtain a composition, which is sieved using a No. 16 sieve (1000 μm) to obtain a sizing powder of 200. got g. As a result of compression molding the sized powder by the method of Example 1 at a tableting pressure of 1000 kgf, 20 tablets of 350 mg per tablet showing a hardness of 10.5 kgf were obtained.
実施例6と同様の方法によりグルコサミンおよびコンドロイチン硫酸の25重量％の水溶液を得た。該水溶液を用いて、実施例1と同様の方法により顆粒を250〜300 g得た。当該顆粒のうち180 gに酵素処理ルチン [αGルチンPS (東洋精糖社製)] 6 g、ショ糖脂肪酸エステル [DKエステルF20W (第一工業製薬社製)] 10 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 4 gを加えて、ポリエチレン袋内で充分に混合して組成物を得て、これを16号篩 (1000 μm) を用いて篩過して整粒末200 gを得た。当該整粒末を実施例1と同様の方法により1000 kgfの打錠圧で圧縮成型を行った結果、10.9 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。 A 25% by weight aqueous solution of glucosamine and chondroitin sulfate was obtained by the same method as in Example 6. Using the aqueous solution, 250 to 300 g of granules were obtained by the same method as in Example 1. 180 g of the granules were treated with enzyme-treated rutin [αG rutin PS (manufactured by Toyo Seisakusho)] 6 g, sucrose fatty acid ester [DK ester F20W (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.)] 10 g and calcium phosphate tribasic [third Calcium phosphate (manufactured by Taihei Kagaku Sangyo Co., Ltd.)] 4 g was added and mixed thoroughly in a polyethylene bag to obtain a composition, which was sieved using a No. 16 sieve (1000 μm) to obtain a granulated powder of 200. got g. As a result of compression molding the sized powder at a tableting pressure of 1000 kgf by the same method as in Example 1, 20 tablets of 350 mg per tablet having a hardness of 10.9 kgf were obtained.
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 320 ｇ、サメ軟骨抽出粉末 [サメ軟骨食品用コンドロイチンHG-40 (日本薬品社製)] 40 ｇおよび酵素処理ルチン [αGルチンPS (東洋精糖社製)] 12 gを精製水1116 mLに溶解して25重量％の水溶液を得た。該水溶液を用いて、実施例1と同様の方法により顆粒、組成物および整粒末を得た後に、850 kgfの打錠圧で圧縮成形を行い、9.5 kgfの硬度を示す錠剤を20錠得た。
［比較例１]
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 320 ｇを精製水960 mLに溶解して25重量％の水溶液を得た。該水溶液を用いて、実施例1と同様の方法により顆粒を得た。当該顆粒160 gに対して、サメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 26 g、ショ糖脂肪酸エステル [DKエステルF20W (第一工業製薬社製)] 10 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 4 gを加えてポリエチレン袋内で充分に混合して組成物を得て、これを16号篩 (1000 μm) を用いて篩過して整粒末を得た。当該整粒末を実施例1と同様の方法により1500 kgfの打錠圧で圧縮成形を行い、6.6 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。
［比較例２]
比較例１と同様の方法によりグルコサミン塩酸塩の25重量％の水溶液を得た。該水溶液を用いて、実施例1と同様の方法により顆粒を得た。当該顆粒160 gに対して、サメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 20 g、酵素処理ルチン [αGルチンPS (東洋精糖社製)] 6 g、ショ糖脂肪酸エステル [DKエステルF20W (第一工業製薬社製)] 10 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 4 gを加えてポリエチレン袋内で充分に混合して組成物を得て、これを16号篩 (1000 μm) を用いて篩過して整粒末を得た。当該整粒末を実施例1との方法により1500 kgfの打錠圧で圧縮成形を行い、6.9 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。
［比較例３]
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 80 gおよびサメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)]13 gを精製水93 mLに懸濁して懸濁液を得た。次いで、真空度 20 mT以下、冷却機温度-80 ℃および棚温度30 ℃の条件に設定したフリーズドライヤー [STD及びBTD Eco トレイドライヤー (FTSSYSTEMS社製)] で、上記懸濁液を15時間乾燥させて顆粒を得た。当該顆粒46.5 gにショ糖脂肪酸エステル [DKエステルF20W (第一工業製薬社製)] 2.5 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 1 gを加えて、ポリエチレン袋内で充分に混合し、本混合末を16号篩 (1000 μm) を用いて篩過して整粒末を得た。当該整粒末を実施例1〜8と同様にして1000 kgfの打錠圧で圧縮成形を行い、8.2 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。
［比較例４]
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 80 g、サメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 13 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 1 gをポリエチレン袋内で充分に混合し、当該混合末を24号篩 (750 μm) を用いて篩過し、流動層造粒機 [流動造粒コーティング装置 FL-MINI型 (フロイント産業社製)] を用いて、20 gの精製水を篩過後の混合末に噴霧して造粒し、顆粒を得た。当該顆粒47 gにショ糖脂肪酸エステル [DKエステルF20W (第一工業製薬社製)] 2.5 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)]を0.5 g加えて、ポリエチレン袋内で充分に混合した。当該混合末を、16号篩 (1000 μm) を用いて篩過して整粒末を得た。当該整粒末を実施例1〜8と同様にして1700 kgfの打錠圧で圧縮成形を行い、6.0 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。
［比較例５]
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 80 g、サメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 10 g、コラーゲン [水溶性フィッシュコラーゲン (協和発酵バイオ社製)] 3 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 1 gをポリエチレン袋内で充分に混合した。比較例4と同様の工程により顆粒および整粒末を得た後、1800 kgfの打錠圧で圧縮成形を行い、6.0 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。
［比較例６］
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 80 g、サメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 10 g、酵素処理ルチン [αGルチンPS (東洋精糖社製)] 3 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 1 gをポリエチレン袋内で充分に混合した。比較例4と同様の工程により顆粒および整粒末を得た後、1700 kgfの打錠圧で圧縮成形を行い、5.0 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。
［比較例７］
グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] 80 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 1 gをポリエチレン袋内で充分に混合した。比較例4と同様の工程により顆粒を得た後、当該顆粒40.5 gにサメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] 5 g、コラーゲン [水溶性フィッシュコラーゲン (協和発酵バイオ社製)] 1.5 g、ショ糖脂肪酸エステル [DKエステルF20W (第一工業製薬社製)] 2.5 gおよび第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] 0.5 gを加えて、ポリエチレン袋内で充分に混合した。当該混合末を16号篩 (1000 μm) を用いて篩過して整粒末を得た。当該整粒末を実施例1〜8と同様にして1800 kgfの打錠圧で圧縮成形を行い、5.5 kgfの硬度を示す1錠あたり350 mgの錠剤を20錠得た。Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 320 g, shark cartilage extract powder [chondroitin HG-40 for shark cartilage food (manufactured by Nippon Yakuhin Co., Ltd.)] 40 g and enzyme-treated rutin [αG rutin PS (Toyo refined sugar) )] 12 g was dissolved in 1116 mL of purified water to obtain a 25 wt% aqueous solution. Using the aqueous solution, granules, composition and sized powder were obtained by the same method as in Example 1, and then compression molding was performed with a tableting pressure of 850 kgf to obtain 20 tablets having a hardness of 9.5 kgf. It was.
[Comparative Example 1]
Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 320 g was dissolved in 960 mL of purified water to obtain a 25 wt% aqueous solution. Using the aqueous solution, granules were obtained by the same method as in Example 1. For 160 g of the granules, shark cartilage extract powder [Marlinker Tillage 40S (manufactured by Yakitsu Fisheries Chemical Co., Ltd.)] 26 g, sucrose fatty acid ester [DK ester F20 W (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.)] 10 g Calcium triphosphate [Tricalcium phosphate (manufactured by Taihei Kagaku Sangyo Co., Ltd.)] Add 4 g and mix well in a polyethylene bag to obtain a composition, which is sieved using a No. 16 sieve (1000 μm). A sized powder was obtained. The sized powder was compression-molded at a tableting pressure of 1500 kgf by the same method as in Example 1, and 20 tablets of 350 mg per tablet showing a hardness of 6.6 kgf were obtained.
[Comparative Example 2]
A 25% by weight aqueous solution of glucosamine hydrochloride was obtained by the same method as in Comparative Example 1. Using the aqueous solution, granules were obtained by the same method as in Example 1. For 160 g of the granules, 20 g of shark cartilage extract powder [Marinker Tillage 40S (manufactured by Yakitsu Fisheries Chemical Co., Ltd.)], 6 g of enzyme-treated rutin [αG rutin PS (manufactured by Toyo Seisakusho)], sucrose fatty acid ester [DK Ester F20W (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.)] 10 g and calcium tertiary phosphate [calcium tertiary phosphate (manufactured by Taihei Kagaku Sangyo Co., Ltd.)] 4 g are added and mixed thoroughly in a polyethylene bag to obtain a composition. , This was sieved using a No. 16 sieve (1000 μm) to obtain a sized powder. The sized powder was compression-molded at a tableting pressure of 1500 kgf by the method of Example 1, and 20 tablets of 350 mg per tablet showing a hardness of 6.9 kgf were obtained.
[Comparative Example 3]
Suspension of 80 g of glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] and 13 g of shark cartilage extract powder [Marinker Tillage 40S (manufactured by YAIZU SUISAN CHEMICAL INDUSTRIES)] in 93 mL of purified water Obtained. Next, the suspension was dried for 15 hours with a freeze dryer [STD and BTD Eco tray dryer (manufactured by FTSSYSTEMS)] set under the conditions of a vacuum degree of 20 mT or less, a cooler temperature of -80 ° C, and a shelf temperature of 30 ° C. Obtained granules. Add 2.5 g of sucrose fatty acid ester [DK ester F20W (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.)] and 1 g of tricalcium phosphate [tritric calcium phosphate (manufactured by Taihei Kagaku Sangyo Co., Ltd.)] to 46.5 g of the granules in a polyethylene bag. The mixture was thoroughly mixed, and the mixed powder was sieved using a No. 16 sieve (1000 μm) to obtain a sized powder. The sized powder was compression-molded at a tableting pressure of 1000 kgf in the same manner as in Examples 1 to 8 to obtain 20 tablets of 350 mg per tablet having a hardness of 8.2 kgf.
[Comparative Example 4]
Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 80 g, shark cartilage extract powder [Marinker Tillage 40S (manufactured by Yakitsu Fisheries Chemical Industry Co., Ltd.)] 13 g and calcium phosphate tribasic [Calcium trimeric phosphate (manufactured by Taihei Chemical Industry Co., Ltd.) (Manufactured)] 1 g is thoroughly mixed in a polyethylene bag, and the mixed powder is sieved using a No. 24 sieve (750 μm), and a fluidized layer granulator [fluid granulator coating device FL-MINI type (Freund) 20 g of purified water was sprayed on the mixed powder after sieving and granulated using (Sangyo Co., Ltd.)] to obtain granules. Add 2.5 g of sucrose fatty acid ester [DK ester F20W (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.)] and 0.5 g of tricalcium phosphate [calcium tri-phosphate (manufactured by Taihei Chemical Industry Co., Ltd.)] to 47 g of the granules in a polyethylene bag. It was mixed well. The mixed powder was sieved using a No. 16 sieve (1000 μm) to obtain a sized powder. The sized powder was compression-molded at a tableting pressure of 1700 kgf in the same manner as in Examples 1 to 8, and 20 tablets of 350 mg per tablet showing a hardness of 6.0 kgf were obtained.
[Comparative Example 5]
Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio)] 80 g, Shark cartilage extract powder [Marinker Tillage 40S (manufactured by Yakitsu Fisheries Chemical Industry Co., Ltd.)] 10 g, Collagen [Water-soluble fish collagen (manufactured by Kyowa Hakko Bio) )] 3 g and calcium tertiary phosphate [calcium tertiary phosphate (manufactured by Taihei Chemical Industry Co., Ltd.)] 1 g were thoroughly mixed in a polyethylene bag. Granules and sized powder were obtained by the same process as in Comparative Example 4, and then compression molding was performed at a tableting pressure of 1800 kgf to obtain 20 tablets of 350 mg per tablet showing a hardness of 6.0 kgf.
[Comparative Example 6]
Glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] 80 g, shark cartilage extract powder [Marinker Tillage 40S (manufactured by Yakitsu Fisheries Chemical Industry Co., Ltd.)] 10 g, enzyme-treated rutin [αG rutin PS (manufactured by Toyo Refinery Co., Ltd.) )] 3 g and calcium tertiary phosphate [calcium tertiary phosphate (manufactured by Taihei Chemical Industry Co., Ltd.)] 1 g were thoroughly mixed in a polyethylene bag. Granules and sized powder were obtained by the same process as in Comparative Example 4, and then compression molding was performed at a tableting pressure of 1700 kgf to obtain 20 tablets of 350 mg per tablet showing a hardness of 5.0 kgf.
[Comparative Example 7]
80 g of glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)] and 1 g of calcium tribasic phosphate [manufactured by Taihei Kagaku Sangyo Co., Ltd.] were thoroughly mixed in a polyethylene bag. After obtaining granules by the same process as in Comparative Example 4, 40.5 g of the granules was added to 40.5 g of shark cartilage extract powder [Mariner Tillage 40S (manufactured by Yakitsu Fisheries Chemical Industry Co., Ltd.)] 5 g, collagen [water-soluble fish collagen (Kyowa Hakko Bio). )] 1.5 g, sucrose fatty acid ester [DK ester F20W (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.)] 2.5 g and calcium tertiary phosphate [calcium tertiary phosphate (manufactured by Taihei Chemical Industry Co., Ltd.)] 0.5 g, and a polyethylene bag It was mixed well in. The mixed powder was sieved using a No. 16 sieve (1000 μm) to obtain a sized powder. The sized powder was compression-molded at a tableting pressure of 1800 kgf in the same manner as in Examples 1 to 8 to obtain 20 tablets of 350 mg per tablet having a hardness of 5.5 kgf.
なお本願実施例および比較例における錠剤の硬度は、実施例１〜８および比較例１〜７の各製造において、製造した錠剤のうちランダムに選んだ5錠の錠剤硬度の平均値を表し、下記表１〜３にその結果を示す。
下記表１中のスプレードライ成分および追加成分、表２中のフリーズドライ成分および追加成分ならびに表３中の造粒成分および追加成分の数値の単位は全て重量％である。The tablet hardnesses in Examples and Comparative Examples of the present application represent the average value of the tablet hardnesses of 5 tablets randomly selected from the produced tablets in each production of Examples 1 to 8 and Comparative Examples 1 to 7, and are as follows. The results are shown in Tables 1 to 3.
The numerical units of the spray-dried components and additional components in Table 1 below, the freeze-dried components and additional components in Table 2, and the granulation components and additional components in Table 3 are all weight%.
下記表１〜３中のGは、グルコサミン塩酸塩 [グルコサミンFM (協和発酵バイオ社製)] を表し、Aはサメ軟骨抽出粉末 [マリンカーティリッジ40S (焼津水産化学工業社製)] を表し、Bは、サメ軟骨抽出粉末[SCP(NB) (マルハニチロ社製)] を表し、Cはサメ軟骨抽出粉末 [サメ軟骨食品用コンドロイチンHG-40 (日本薬品社製)]、Dは、コラーゲン [水溶性フィッシュコラーゲン (協和発酵バイオ社製)] を表し、Eは、酵素処理ルチン [αGルチンPS (東洋精糖社製)] を表し、Fは、ショ糖脂肪酸エステル[DKエステルF20W (第一工業製薬社製)] を表し、Hは、第三リン酸カルシウム [第三リン酸カルシウム (太平化学産業社製)] を表す。 In Tables 1 to 3 below, G represents glucosamine hydrochloride [Glucosamine FM (manufactured by Kyowa Hakko Bio Co., Ltd.)], and A represents shark cartilage extract powder [Marinker Tillage 40S (manufactured by Yakitsu Fisheries Chemical Industry Co., Ltd.)]. B stands for shark cartilage extract powder [SCP (NB) (manufactured by Maruhanichiro)], C stands for shark cartilage extract powder [chondroitin HG-40 for shark cartilage food (manufactured by Nippon Yakuhin Co., Ltd.)], and D stands for collagen [water-soluble]. Sex fish cartilage (manufactured by Kyowa Hakko Bio Co., Ltd.)], E stands for enzyme-treated rutin [αG rutin PS (manufactured by Toyo Seiko Co., Ltd.)], and F stands for sucrose fatty acid ester [DK ester F20W (Daiichi Kogyo Seiyaku Co., Ltd.) (Manufactured by Taihei Kagaku Sangyo Co., Ltd.)], and H represents calcium tertiary phosphate (manufactured by Taihei Kagaku Sangyo Co., Ltd.).
下記表１〜３中の「キャッピング」における○は、当該実施例または比較例の製造において、20錠打錠した際に1錠もキャッピングが発生しなかったことを表し、×は、20錠打錠した際に1錠以上キャッピングが発生したことを表す。
下記表１〜３中の「流動性」における○は、単発式圧縮成型機において、篩過した混合末の充填時に、1回のすり切りで篩過した混合末がスムーズに充填されたことを示し、×は、単発式圧縮成型機において、少なくとも1回のすり切りでは、篩過した混合末がスムーズに充填されなかったことを示す。In the "capping" in Tables 1 to 3 below, ○ indicates that no capping occurred when 20 tablets were locked in the production of the Example or Comparative Example, and × indicates 20 tablets. Indicates that one or more tablets have been capped when locked.
○ in “fluidity” in Tables 1 to 3 below indicates that the mixed powder sifted by one grinding was smoothly filled when the mixed powder sifted was filled in the single-engine compression molding machine. , X indicates that in the single-engine compression molding machine, the sieved mixed powder was not smoothly filled by at least one grinding.
上記実施例１〜８で得られた錠剤について、少なくともグルコサミン塩酸塩およびサメ軟骨抽出粉末を水に溶解してスプレードライした実施例１〜８では流動性が十分であり、キャッピングまたはラミネーションを生じることなく錠剤が得られた。一方、グルコサミンのみをスプレードライした比較例１および２ならびに流動層造粒で造粒成分を造粒した比較例４〜７では、流動性は十分であったが、キャッピングが生じた。また、グルコサミン塩酸塩およびサメ軟骨抽出粉末をフリーズドライした比較例3は、キャッピングは生じなかったが、流動性が不十分であった。 With respect to the tablets obtained in Examples 1 to 8 above, at least in Examples 1 to 8 in which at least glucosamine hydrochloride and shark cartilage extract powder are dissolved in water and spray-dried, the fluidity is sufficient and capping or lamination occurs. No tablets were obtained. On the other hand, in Comparative Examples 1 and 2 in which only glucosamine was spray-dried and Comparative Examples 4 to 7 in which the granulation component was granulated by fluidized bed granulation, the fluidity was sufficient, but capping occurred. In Comparative Example 3 in which glucosamine hydrochloride and shark cartilage extract powder were freeze-dried, capping did not occur, but the fluidity was insufficient.
従って、本願発明により、打錠性および流動性が向上したグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒、組成物およびそれらを用いることによりグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を高含有する錠剤が得られることが分かった。 Therefore, according to the present invention, glucosamine or a salt thereof and chondroitin sulfate or a salt thereof containing improved tableting property and fluidity, and granules, compositions containing them, and glucosamine or a salt thereof and chondroitin sulfate or a salt thereof can be increased by using them. It was found that a tablet containing it was obtained.
本発明により、打錠性および流動性が向上したグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒および組成物、ならびにグルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を高含有する錠剤およびその製造方法が提供される。 According to the present invention, granules and compositions containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof having improved tableting property and fluidity, and tablets and a tablet having a high content of glucosamine or a salt thereof and chondroitin sulfate or a salt thereof and the like. The method is provided.
Claims (4)
溶液１または２に含まれるグルコサミンまたはその塩の含有量が１８〜２４重量％であり、溶液１または２に含まれるコンドロイチン硫酸またはその塩の含有量が１．８〜４．０重量％である、グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する顆粒の製造方法。 A solution or suspension containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof (hereinafter, the solution or suspension is abbreviated as solution 1) , or in addition to the solution 1, collagen or an enzyme-treated product thereof, rutin or its Spray dry a solution or suspension (hereinafter, the solution or suspension is abbreviated as Solution 2) containing one or more compounds selected from the group consisting of an enzyme-treated product, thiamine, riboflavin, pyridoxin, niacin and pantothenic acid. A method for producing granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, which comprises a step of:
The content of glucosamine or a salt thereof contained in solution 1 or 2 is 18 to 24% by weight, and the content of chondroitin sulfate or a salt thereof contained in solution 1 or 2 is 1.8 to 4.0% by weight. , A method for producing granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof.
溶液１または２に含まれるグルコサミンまたはその塩の含有量が１８〜２４重量％であり、溶液１または２に含まれるコンドロイチン硫酸またはその塩の含有量が１．８〜４．０重量％である、グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する組成物の製造方法。 One or more selected from the group consisting of a lubricant, a fluidity improver and an additive in the step of spray-drying the solution 1 or 2 and the granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof obtained in the step. A method for producing a composition containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, which comprises a step of adding the compound of.
The content of glucosamine or a salt thereof contained in solution 1 or 2 is 18 to 24% by weight, and the content of chondroitin sulfate or a salt thereof contained in solution 1 or 2 is 1.8 to 4.0% by weight. , A method for producing a composition containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof.
溶液１または２に含まれるグルコサミンまたはその塩の含有量が１８〜２４重量％であり、溶液１または２に含まれるコンドロイチン硫酸またはその塩の含有量が１．８〜４．０重量％である、グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する錠剤の製造方法。 Glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, which comprises a step of spray-drying solution 1 or solution 2 and a step of tableting with granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof obtained in the step. A method for producing the contained tablets.
The content of glucosamine or a salt thereof contained in solution 1 or 2 is 18 to 24% by weight, and the content of chondroitin sulfate or a salt thereof contained in solution 1 or 2 is 1.8 to 4.0% by weight. , A method for producing a tablet containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof.
溶液１または２に含まれるグルコサミンまたはその塩の含有量が１８〜２４重量％であり、溶液１または２に含まれるコンドロイチン硫酸またはその塩の含有量が１．８〜４．０重量％である、グルコサミンまたはその塩およびコンドロイチン硫酸またはその塩を含有する錠剤の製造方法。 A step of spray-drying solution 1 or solution 2, one selected from the group consisting of a lubricant, a fluidity improver and an additive in granules containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof obtained in the step. Contains glucosamine or a salt thereof and chondroitin sulfate or a salt thereof, which comprises a step of adding and mixing the above compounds and a step of tableting a composition containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof obtained in the step. It is a method of manufacturing tablets.
The content of glucosamine or a salt thereof contained in solution 1 or 2 is 18 to 24% by weight, and the content of chondroitin sulfate or a salt thereof contained in solution 1 or 2 is 1.8 to 4.0% by weight. , A method for producing a tablet containing glucosamine or a salt thereof and chondroitin sulfate or a salt thereof.
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