JP5367328B2 - Carnitine-containing preparation - Google Patents
Carnitine-containing preparation Download PDFInfo
- Publication number
- JP5367328B2 JP5367328B2 JP2008223559A JP2008223559A JP5367328B2 JP 5367328 B2 JP5367328 B2 JP 5367328B2 JP 2008223559 A JP2008223559 A JP 2008223559A JP 2008223559 A JP2008223559 A JP 2008223559A JP 5367328 B2 JP5367328 B2 JP 5367328B2
- Authority
- JP
- Japan
- Prior art keywords
- carnitine
- tartrate
- porous
- dextrin
- hygroscopicity
- 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.)
- Active
Links
- 229960004203 carnitine Drugs 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 title 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims abstract description 64
- 229920002472 Starch Polymers 0.000 claims abstract description 19
- 239000008107 starch Substances 0.000 claims abstract description 19
- 235000019698 starch Nutrition 0.000 claims abstract description 19
- RZALONVQKUWRRY-XOJLQXRJSA-N (2r,3r)-2,3-dihydroxybutanedioate;hydron;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O RZALONVQKUWRRY-XOJLQXRJSA-N 0.000 claims description 23
- 229920001353 Dextrin Polymers 0.000 claims description 22
- 239000004375 Dextrin Substances 0.000 claims description 22
- 235000019425 dextrin Nutrition 0.000 claims description 22
- 239000002775 capsule Substances 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 5
- 239000004382 Amylase Substances 0.000 claims description 3
- 102000013142 Amylases Human genes 0.000 claims description 3
- 108010065511 Amylases Proteins 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 235000019418 amylase Nutrition 0.000 claims description 3
- 238000000354 decomposition reaction Methods 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000007963 capsule composition Substances 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 abstract description 14
- 239000000843 powder Substances 0.000 abstract description 12
- 235000013305 food Nutrition 0.000 abstract description 9
- 230000006866 deterioration Effects 0.000 abstract description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 abstract description 4
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 17
- 239000000546 pharmaceutical excipient Substances 0.000 description 13
- 238000000034 method Methods 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 9
- 238000002156 mixing Methods 0.000 description 7
- -1 sex Chemical compound 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000007902 hard capsule Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000007857 degradation product Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 4
- 235000011613 Pinus brutia Nutrition 0.000 description 4
- 241000018646 Pinus brutia Species 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 235000013339 cereals Nutrition 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 238000002845 discoloration Methods 0.000 description 3
- 235000013402 health food Nutrition 0.000 description 3
- 238000007711 solidification Methods 0.000 description 3
- 230000008023 solidification Effects 0.000 description 3
- PEYUIKBAABKQKQ-AFHBHXEDSA-N (+)-sesamin Chemical compound C1=C2OCOC2=CC([C@H]2OC[C@H]3[C@@H]2CO[C@@H]3C2=CC=C3OCOC3=C2)=C1 PEYUIKBAABKQKQ-AFHBHXEDSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010058892 Carnitine deficiency Diseases 0.000 description 2
- 240000003183 Manihot esculenta Species 0.000 description 2
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- HNSUOMBUJRUZHJ-REVJHSINSA-N [(2r)-3-carboxy-2-hydroxypropyl]-trimethylazanium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound OC(=O)\C=C/C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O HNSUOMBUJRUZHJ-REVJHSINSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- PEYUIKBAABKQKQ-UHFFFAOYSA-N epiasarinin Natural products C1=C2OCOC2=CC(C2OCC3C2COC3C2=CC=C3OCOC3=C2)=C1 PEYUIKBAABKQKQ-UHFFFAOYSA-N 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- VRMHCMWQHAXTOR-CMOCDZPBSA-N sesamin Natural products C1=C2OCOC2=CC([C@@H]2OC[C@@]3(C)[C@H](C=4C=C5OCOC5=CC=4)OC[C@]32C)=C1 VRMHCMWQHAXTOR-CMOCDZPBSA-N 0.000 description 2
- 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 description 2
- AUSHDAODAXKKDJ-FYZOBXCZSA-N (3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate;magnesium Chemical compound [Mg].C[N+](C)(C)C[C@H](O)CC([O-])=O AUSHDAODAXKKDJ-FYZOBXCZSA-N 0.000 description 1
- SVVSJSVMXCEDDA-FYZOBXCZSA-N (3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate;oxalic acid Chemical compound OC(=O)C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O SVVSJSVMXCEDDA-FYZOBXCZSA-N 0.000 description 1
- RZALONVQKUWRRY-FYZOBXCZSA-N 2,3-dihydroxybutanedioic acid;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound OC(=O)C(O)C(O)C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O RZALONVQKUWRRY-FYZOBXCZSA-N 0.000 description 1
- VOTPLFCPIRIALF-UHFFFAOYSA-N 3-(2,4-dioxo-1h-pyrimidine-6-carbonyl)oxy-4-(trimethylazaniumyl)butanoate Chemical compound C[N+](C)(C)CC(CC([O-])=O)OC(=O)C1=CC(=O)NC(=O)N1 VOTPLFCPIRIALF-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000001019 Inborn Errors Metabolism Diseases 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 description 1
- UFAHZIUFPNSHSL-MRVPVSSYSA-N O-propanoyl-L-carnitine Chemical compound CCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C UFAHZIUFPNSHSL-MRVPVSSYSA-N 0.000 description 1
- 241000237509 Patinopecten sp. Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 0.000 description 1
- GUBGYTABKSRVRQ-ASMJPISFSA-N alpha-maltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-ASMJPISFSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- PHIQHXFUZVPYII-UHFFFAOYSA-N carnitine Chemical compound C[N+](C)(C)CC(O)CC([O-])=O PHIQHXFUZVPYII-UHFFFAOYSA-N 0.000 description 1
- 229960000678 carnitine chloride Drugs 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000003278 egg shell Anatomy 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000016245 inborn errors of metabolism Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000015978 inherited metabolic disease Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 235000020637 scallop Nutrition 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、カルニチン含有製剤に関する。 The present invention relates to a carnitine-containing preparation.
L-カルニチンは、リジンとメチオニンと言う２つのアミノ酸から肝臓や腎臓で作られる生体微量成分で、20代をピークに年齢とともにその生成量は低下することが知られている。L-カルニチンは、筋肉細胞へ長鎖脂肪酸の受け渡しなど栄養成分の代謝に重要な働きをしており、日本では医薬品として用いられていたが、2002年12月より食品としての利用が認められたことから、体内で脂肪酸燃焼に重要な関わりを持つL-カルニチンの生理機能に着目した「いわゆる健康食品」が、体脂肪燃焼効果を期待するダイエット食品として注目されている。厚生労働省は、１日あたりの摂取上限の目安量を約1000mgとしている。人におけるL-カルニチンの生理的有効性は、腎機能改善効果、甲状腺機能改善効果、 抗けいれん薬（抗てんかん薬）であるバルプロ酸によるカルニチン欠乏の軽減効果、先天性代謝異常によるカルニチン欠乏症に対する有効性など、臨床的なL-カルニチンの利用の多くは、欠乏症を補うために投与する事例が多い。L-カルニチンは薬として使用されてきた経験が長く、また生体成分でもあることから、安全性上大きな問題は生じないと考えられている。
近頃、L-カルニチンを適切に摂取することを目的として、栄養補助食品、食事療法用製品、健康食品等の飲食品又は飲食品用組成物に使用されている。カルニチンを配合したサプリメントは、一日の摂取量として５００〜６００ｍｇを目安としているものが多い。一方、カルニチンは吸湿性が高い物質であるので、安定を確保するために賦形剤などの他の成分の配合率が高く、目安の量を摂取するには、カルニチン配合剤を多量に経口摂取することとなるのが、実情である。
カルニチンなどの吸湿性の高い物質は、吸湿が製造中に発生すると、流動特性の変化、粘着性の増加、凝集の発生、離型性の低下という問題が生じ、取扱いが困難になるばかりか、化学的安定性が低下して原料や製品の組成が変動することもある。また、吸湿が貯蔵中に発生すると、外観の劣化だけでなく、含有活性成分の化学的安定性の低下や結晶形態の変化による溶解特性の変化等の問題が生じることがあるので、吸湿性を改善する工夫がなされている。
L-carnitine is a biological trace component made by the liver and kidney from two amino acids called lysine and methionine, and its production amount is known to decrease with age at the peak of 20s. L-carnitine plays an important role in the metabolism of nutritional components such as delivery of long-chain fatty acids to muscle cells, and was used as a pharmaceutical in Japan, but has been approved for use as a food since December 2002. Therefore, “so-called health foods” that focus on the physiological function of L-carnitine, which has an important role in fatty acid combustion in the body, are attracting attention as diet foods that are expected to have a body fat burning effect. The Ministry of Health, Labor and Welfare sets a standard amount of upper limit of intake per day to about 1000 mg. The physiological effectiveness of L-carnitine in humans is to improve renal function, improve thyroid function, alleviate carnitine deficiency with valproic acid, an anticonvulsant (antiepileptic drug), and effective against carnitine deficiency due to inborn errors of metabolism Many clinical uses of L-carnitine, such as sex, are often administered to compensate for deficiencies. L-carnitine has long been used as a medicine and is also a biological component, so it is considered that no major safety problems will occur.
Recently, for the purpose of appropriately taking L-carnitine, it has been used in foods and beverages or food and beverage compositions such as dietary supplements, diet products, and health foods. Many supplements containing carnitine have a daily intake of 500 to 600 mg as a guide. On the other hand, carnitine is a highly hygroscopic substance, so the content of other ingredients such as excipients is high to ensure stability. It is the actual situation that will be done.
Substances with high hygroscopicity such as carnitine, when moisture absorption occurs during production, causes problems such as change in flow characteristics, increase in stickiness, occurrence of aggregation, decrease in releasability, and handling becomes difficult. Chemical stability may decrease and the composition of raw materials and products may fluctuate. In addition, when moisture absorption occurs during storage, problems such as deterioration in appearance, chemical stability of the active ingredient contained, and changes in dissolution characteristics due to changes in crystal form may occur. There is a device to improve.
有機酸又は無機酸の塩類、無機塩類及び薬剤等に用いられる化合物原料等製造時や使用時の取扱いが難しい吸湿性粉末原料について、その吸湿性や潮解性を解決するための方法が種々提案されている。 例えば、粉状物に粉末状の油脂及び炭酸カルシウムを添加して潮解や固結を防止する方法(特許文献１)、ショ糖脂肪酸エステルを添加して固結を防止する方法(特許文献２)、吸着性物質に潮解性物質を吸着させ潮解を防止する方法(特許文献３)、吸湿性を有する粉末原料を腸溶性皮膜剤で被覆した粉末改良品(特許文献４)、結晶形態を変化させることにより潮解性を遅くさせる方法(特許文献５)等が開示されている。 Various methods for solving hygroscopicity and deliquescence have been proposed for hygroscopic powder raw materials that are difficult to handle at the time of manufacture or use, such as organic acid or inorganic acid salts, compound salts used in inorganic salts and drugs, etc. ing. For example, a method for preventing deliquescence and caking by adding powdered fats and calcium carbonate to a powder (Patent Document 1), a method for preventing caking by adding sucrose fatty acid ester (Patent Document 2) , A method for preventing deliquescence by adsorbing a deliquescent substance to an adsorbent substance (Patent Document 3), a powder improved product obtained by coating a hygroscopic powder raw material with an enteric coating agent (Patent Document 4), and changing the crystal form A method of slowing deliquescence by this (Patent Document 5) and the like are disclosed.
高い吸湿性を有し、極めて安定性が低いL-カルニチンについても、吸湿性を押さえ、安定化する工夫が各種提案されている。
特許文献６には、L-カルニチンに代わってL-カルニチンL-酒石酸塩による吸湿抑制方法が提示されている。L-カルニチンL-酒石酸塩はカルニチン（化１）を68％含む白色の結晶であり、L-カルニチンよりも安定性は良いとされる。
しかし、依然として非常に高い吸湿性・潮解性を有していて、25℃湿度63％以上の環境下で吸湿・潮解し、その吸湿速度は非常に高い。またカルニチン若しくはその塩又はその誘導体は、潮解や温度による劣化、アルカリ下における分解によってトリメチルアミンを発生し、少量で強烈な悪臭を発生する。L-カルニチンL-酒石酸塩も吸湿により同様の悪臭を発生する。
Various ideas have been proposed to suppress and stabilize the hygroscopic property of L-carnitine having high hygroscopic property and extremely low stability.
Patent Document 6 proposes a moisture absorption suppressing method using L-carnitine L-tartrate instead of L-carnitine. L-carnitine L-tartrate is a white crystal containing 68% carnitine (Chemical Formula 1), and is considered to be more stable than L-carnitine.
However, it still has very high hygroscopicity and deliquescence, and absorbs and deliquesces in an environment with a humidity of 25% and a humidity of 63% or higher, and its moisture absorption rate is very high. Carnitine or a salt thereof or a derivative thereof generates trimethylamine by deliquescence, deterioration due to temperature, or decomposition under alkali, and generates a strong odor in a small amount. L-carnitine L-tartrate also produces a similar malodor due to moisture absorption.
L-カルニチンL-酒石酸塩のような粉末吸湿活性成分を高含有させた製剤を製造する場合、その吸湿性の高さから、上記のように得られた製剤が変色・変性したりすることが問題視されている。このような問題は、賦形剤を増量することで解決することがあるが、賦形剤を増量すると、一日当たりに摂取する量は非常に多くなることから、賦形剤のような活性成分以外の配合量を極力少なくすることが望ましい。
特許文献７（特開2007-244270号公報）には、錠剤・顆粒剤にセサミンを加えることでL-カルニチンL-酒石酸塩の吸湿性を抑える提案がなされている。しかし、具体的には、セサミン類のほかに必要な賦形剤量が多く、高配合化を可能にするものではない。
特許文献８（特開2004−135515号公報）には、酢酸カルシウム添加法による吸湿抑制効果が開示されているが、添加量10〜95重量％において有効であり、10重量％以下では効果が低くなるとされ、高配合化には適さない。
特許文献９（特開2006−111550号公報）には、カルニチン含有製剤(錠剤)をシェラックコーティングし、更にイーストラップで被覆して防湿する方法も提案されているが、簡便さに欠けるのが難点である。
特許文献１０（再公表2006-28068号公報）には、粗結晶L-カルニチンを低級アルキルアルコールと水との混合溶媒に溶解させた後、再結晶させるにより、粒径が大きく吸湿性を低下させたL-カルニチンが開示されている。
When producing a preparation containing a high amount of powder hygroscopic active ingredient such as L-carnitine L-tartrate, the preparation obtained as described above may be discolored or denatured due to its high hygroscopicity. It is regarded as a problem. Such problems may be solved by increasing the amount of excipient. However, if the amount of excipient is increased, the amount consumed per day becomes very large. It is desirable to reduce the blending amount other than as much as possible.
Patent Document 7 (Japanese Patent Laid-Open No. 2007-244270) proposes to suppress the hygroscopicity of L-carnitine L-tartrate by adding sesamin to tablets and granules. However, specifically, in addition to sesamin, a large amount of excipient is necessary, which does not enable high compounding.
Patent Document 8 (Japanese Patent Application Laid-Open No. 2004-135515) discloses a moisture absorption suppressing effect by the calcium acetate addition method, but is effective at an addition amount of 10 to 95% by weight, and less effective at 10% by weight or less. Therefore, it is not suitable for high blending.
Patent Document 9 (Japanese Patent Application Laid-Open No. 2006-111550) proposes a method of coating a carnitine-containing preparation (tablet) with shellac and further covering with a yeast wrap to prevent moisture, but it is difficult to be convenient. It is.
Patent Document 10 (Republished No. 2006-28068) discloses that crude crystal L-carnitine is dissolved in a mixed solvent of lower alkyl alcohol and water and then recrystallized to reduce the hygroscopicity by increasing the particle size. L-carnitine has been disclosed.
本発明は、吸湿性が高く潮解性を有し、高温多湿下において容易に吸湿・液状になってしまうカルニチン若しくはその塩又はその誘導体を、賦形剤を多量に配合することなく安定化したカルニチン高含有製剤を提供することを課題とする。 The present invention provides carnitine that has high hygroscopicity, has deliquescence, and has stabilized carnitine or a salt thereof or a derivative thereof that easily becomes hygroscopic and liquid under high temperature and high humidity without blending a large amount of excipients. It is an object to provide a high-content preparation.
本発明者の主な構成は次のとおりである。
（１）Ｌ−カルニチン若しくはＬ−カルニチンＬ−酒石酸塩及び、多孔質デキストリンを含み、
重量比率においてＬ−カルニチン若しくはＬ−カルニチンＬ−酒石酸塩：多孔質デキストリン＝８０〜９５：２０〜５であって、
前記多孔質デキストリンがデキストリンの粒子表面に微細孔を形成させた形状的な特徴を有するものであることを特徴とするカルニチン含有カプセル製剤。
（２）Ｌ−カルニチン若しくはＬ−カルニチンＬ−酒石酸塩及び、多孔質デキストリンを含み、
重量比率においてＬ−カルニチン若しくはＬ−カルニチンＬ−酒石酸塩：多孔質デキストリン＝８０〜９５：２０〜５であって、
前記多孔質デキストリンがデンプンを酸又はアミラーゼで分解して得られる分解生成物を加熱したローラー上に乗せ、溶媒を蒸発させることにより得ることができるものであることを特徴とするカルニチン含有カプセル製剤。
The main configuration of the present inventor is as follows.
(1) L-carnitine or L-carnitine L-tartrate and porous dextrin ,
L-carnitine or L-carnitine L-tartrate: porous dextrin = 80-95: 20-5 in weight ratio,
A carnitine-containing capsule preparation characterized in that the porous dextrin has a shape characteristic in which micropores are formed on the particle surface of the dextrin .
(2) L-carnitine or L-carnitine L-tartrate and porous dextrin,
L-carnitine or L-carnitine L-tartrate: porous dextrin = 80-95: 20-5 in weight ratio,
Carnitine-containing capsule formulation, characterized in that said porous dextrin is placed on a roller heated decomposition product obtained by decomposing the starch with acid or amylase, in which the solvent can be obtained by evaporation.
本発明においては、多孔質デンプンを、配合することによりカルニチン若しくはその塩又はその誘導体の安定性を大幅に改善し、９０％以上の高配合を実現できる。多孔質デンプンとして多孔質性デキストリンが好ましい。カルニチンの塩として、L-カルニチンL-酒石酸塩が好ましい。多孔質デンプンは、５〜６重量％加えるのみであり、非常に簡便かつ安価な方法であることが特徴である。
カルニチンを安定化した粉末として扱うことができるので、原材料としての保存性、製造過程のハンドリングの向上、製剤や食品製品としての保存性が向上する。吸湿性が押さえられて安定化しているので、他の剤との混合操作が容易であり均一した配合剤を得ることができる。カルニチンの摂取目安量を満足する経口摂取用の剤形を小型化することができ、摂取が容易となる。特に、嚥下力が弱っている高齢者などには適している。
In the present invention, the stability of carnitine or a salt thereof or a derivative thereof is greatly improved by blending porous starch, and a high blending of 90% or more can be realized. A porous dextrin is preferred as the porous starch. As the carnitine salt, L-carnitine L-tartrate is preferred. Porous starch is only 5 to 6% by weight, and is characterized by a very simple and inexpensive method.
Since carnitine can be handled as a stabilized powder, storage stability as a raw material, improved handling of the manufacturing process, and storage stability as a preparation or food product are improved. Since the hygroscopicity is suppressed and stabilized, the mixing operation with other agents is easy and a uniform compounding agent can be obtained. The dosage form for oral intake that satisfies the recommended intake of carnitine can be reduced in size, and the intake becomes easier. It is particularly suitable for elderly people with weak swallowing power.
本発明のカルニチン含有製剤は、カルニチン若しくはその塩又はその誘導体、及び、多孔質デンプンからなることにより、吸湿性を抑制し安定化した粉末状態を提供することができる。この安定化した粉末状態を利用して、更に他の剤との均一混合や製剤化の工程管理を容易に行うことができ、少量且つ小型化した剤形を提供する。 The carnitine-containing preparation of the present invention comprises carnitine or a salt thereof or a derivative thereof and a porous starch, thereby providing a powder state in which hygroscopicity is suppressed and stabilized. By utilizing this stabilized powder state, it is possible to easily carry out uniform mixing with other agents and process control of formulation, and provide a small and small-sized dosage form.
カルニチン若しくはその塩又はその誘導体とは、カルニチン[(CH3)3N+CH2CH(OH)CH2COO-、γ-トリメチルアンモニウム-β-ヒドロキシ酪酸]、その異性体、その塩、並びにカルニチン、その異性体及びその塩の誘導体（例えば生体内でカルニチンに変換される誘導体）も含む。例えば、カルニチン、L-カルニチン、塩化カルニチン（DL-体、L-体）、L-カルニチン酒石酸塩、L-カルニチンL-酒石酸塩、L-カルニチンマレイン酸塩、L-カルニチンフマル酸塩、L-カルニチン硫酸塩、L-カルニチンシュウ酸塩、L-カルニチンマグネシウム塩、アシル-L-カルニチン、アセチル-L-カルニチン、プロピオニル-L-カルニチン、オロチン酸カルニチン、等が含まれる。これらはその製造方法になんら限定されず、天然抽出品、微生物発酵品、合成品のいずれでもよいが、好ましくは、天然に存在するL-カルニチン若しくはその塩又はその誘導体であり、例えば、次式： Carnitine or a salt thereof or a derivative thereof includes carnitine [(CH3) 3N + CH2CH (OH) CH2COO-, γ-trimethylammonium-β-hydroxybutyric acid], its isomer, its salt, and carnitine, its isomer and its derivative Also included are derivatives of salts (for example, derivatives that are converted to carnitine in vivo). For example, carnitine, L-carnitine, carnitine chloride (DL-form, L-form), L-carnitine tartrate, L-carnitine L-tartrate, L-carnitine maleate, L-carnitine fumarate, L-carnitine Examples include sulfate, L-carnitine oxalate, L-carnitine magnesium salt, acyl-L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine, carnitine orotate, and the like. These are not limited to the production method, and may be any of natural extracts, microbial fermented products, and synthetic products, but are preferably naturally occurring L-carnitine or a salt thereof or a derivative thereof. :
(式中、RはH又はC1〜C5の低級アルカノイルである。)
で表される。なお、本明細書中のカルニチンについての説明は、カルニチンの塩、カルニチン又はその塩の誘導体についてもあてはまる。
(In the formula, R is H or C1-C5 lower alkanoyl.)
It is represented by Note that the description of carnitine in the present specification also applies to a carnitine salt, carnitine or a salt derivative thereof.
多孔質デンプンは、とうもろこし、馬鈴薯、タピオカ、小麦等のデンプンの粒子表面に無数の微細孔を形成させた形状的な特徴を有する。
特に、多孔質性デキストリンが適している。「多孔質性デキストリン」とは、とうもろこし、馬鈴薯、タピオカ、小麦等のデンプンの粒子に酵素を作用させることにより、該粒子の表面に無数の微細孔を形成させた形状的な特徴を有する。
デキストリンとは、デンプンを酸又はアミラーゼで分解して得られる分解生成物の総称であり、アミロデキストリン、マルトデキストリン、エリトロデキストリンなどがある。また、多孔質デキストリンは、強力に加熱したローラー上にデキストリン溶液を乗せ、瞬時に溶媒を蒸発させることにより得ることができる。本発明に用いる多孔質デキストリンの市販品としては、パインフロー、パインフローＳ（共に、松谷化学社製）等が挙げられる。
Porous starch has shape characteristics in which numerous fine pores are formed on the surface of starch particles such as corn, potato, tapioca, and wheat.
In particular, porous dextrin is suitable. “Porous dextrin” has a shape characteristic in which countless micropores are formed on the surface of starch particles such as corn, potato, tapioca, and wheat by causing an enzyme to act.
Dextrin is a general term for degradation products obtained by degrading starch with acid or amylase, and includes amylodextrin, maltodextrin, erythrodextrin and the like. Porous dextrin can be obtained by placing a dextrin solution on a roller heated strongly and instantly evaporating the solvent. Examples of commercially available porous dextrin used in the present invention include Pine Flow and Pine Flow S (both manufactured by Matsutani Chemical Co., Ltd.).
カルニチンに多孔質若しくはその塩又はその誘導体、及び、多孔質デンプンからなる、カルニチン含有製剤は、含有比率を重量比率においてカルニチン若しくはその塩又はその誘導体：多孔質デンプン＝８０〜９５：２０〜５とすることができる。
本発明は吸湿性が改善された安定した粉末状として提供することができ、これを必要に応じて他の剤を添加するなどして、製剤化することができる。本発明は、従来から用いられている医薬用、あるいは、栄養補助食品、食事療法用製品、健康食品等の飲食品又は飲食品用組成物に使用することができる。
A carnitine-containing preparation comprising a carnitine porous or a salt thereof or a derivative thereof and a porous starch has a content ratio of carnitine or a salt thereof or a derivative thereof: porous starch = 80 to 95:20 to 5 in a weight ratio. can do.
The present invention can be provided as a stable powder with improved hygroscopicity, and can be formulated by adding other agents as necessary. INDUSTRIAL APPLICABILITY The present invention can be used for conventionally used pharmaceutical or food / beverage products or food / beverage food compositions such as dietary supplements, diet products, and health foods.
小型化したハードカプセルとして経口摂取するタイプに適している。L-カルニチンL-酒石酸塩を高配合９２％しながらも安定なハードカプセル製剤を作製することができる。例えば、本発明品は２号ハードカプセル×３粒で目安の６００mg以上のL-カルニチンを十分に摂取できる。２号ハードカプセルには、３２０ｍｇ程度封入することができるので、L-カルニチンを６８％含んでいるL-カルニチンL-酒石酸塩を９２重量％配合したカルニチン含有製剤を詰めることにより、L-カルニチン換算量を２００ｍｇ／２号ハードカプセル１粒とすることができる。
尚、従来品においては、耐湿性を確保するため賦形剤を多く配合する必要があり、L-カルニチンL-酒石酸塩の配合量は多くとも７０重量％程度、カプセルが大きい(１号)あるいは、粒数が多い(４粒以上)のが現状である。L-カルニチンL-酒石酸塩等のカルニチンは、非常に吸湿性が高く潮解性を有し、高温多湿下において容易に吸湿・液状になってしまうため、多量の賦形剤を配合することで耐湿性を付与する必要があり、多量の賦形剤を配合することで、錠剤やカプセルのサイズが大きくなる、あるいは数が増え、飲み易さという点において大きなマイナスであった。本発明では、小型カプセルで且つ摂取粒数を少なくすることができる。
It is suitable for the type that is taken orally as a miniaturized hard capsule. A stable hard capsule preparation can be produced while containing 92% of L-carnitine L-tartrate in a high proportion. For example, the product of the present invention can sufficiently take L-carnitine of 600 mg or more as a guide with No. 2 hard capsules × 3 capsules. No. 2 hard capsule can contain about 320 mg, so by filling a carnitine-containing preparation containing 92% by weight of L-carnitine L-tartrate containing 68% of L-carnitine, the equivalent amount of L-carnitine Can be made into one 200 mg / 2 hard capsule.
In addition, in the conventional product, it is necessary to mix many excipients in order to ensure moisture resistance, and the amount of L-carnitine L-tartrate is about 70% by weight at most and the capsule is large (No. 1) or Currently, the number of grains is large (4 grains or more). Carnitine such as L-carnitine L-tartrate is very hygroscopic and deliquescent, and easily becomes hygroscopic and liquid under high temperature and high humidity. It was necessary to impart a high level of functionality, and by adding a large amount of excipients, the size of tablets and capsules increased, or the number increased, which was a big negative in terms of ease of drinking. In the present invention, it is a small capsule and the number of ingested grains can be reduced.
本明細書中において、「吸湿性」とは、対象物が空気中にさらされている場合に大気中の水蒸気を捉える性質をいい、特に、潮解性と呼ばれる、大気中の水蒸気を取り込んで水溶液になる性質も、本明細書中における「吸湿性」に含まれる。
吸湿性は、例えば、後述の実施例に記載のような、当業者に公知の手法を用いて、測定及び／又は評価することができる。具体的には、計量した原料を、室温や高温高湿度下等の一定条件下、適当な時間放置した後、変化を目視観察(原料表面の水分の確認、固体の消失の確認、粉末の流動性や固結化の程度の確認、変色の確認等)や、重量増加分(吸湿水量)の計量により検討する等の手法を用いることができる。
本明細書中において、「安定化」とは、単に吸湿による潮解及び／又は固結が防止されるということだけではなく、変色・異臭（悪臭）の発生が認められず、品質的に経口・外用剤としての使用に問題が認められないことをいう。
In this specification, “hygroscopicity” refers to the property of capturing water vapor in the atmosphere when an object is exposed to the air. In particular, an aqueous solution that captures water vapor in the atmosphere, called deliquescence. This property is also included in the “hygroscopicity” in the present specification.
Hygroscopicity can be measured and / or evaluated using techniques known to those skilled in the art, for example, as described in the examples below. Specifically, the measured raw material is allowed to stand for a suitable time under certain conditions such as room temperature or high temperature and high humidity, and then visually observed for changes (confirmation of moisture on the raw material surface, confirmation of disappearance of solids, powder flow For example, confirmation of the degree of solidification and solidification, confirmation of discoloration, etc.) and measurement by measuring the weight increase (amount of absorbed water).
In this specification, “stabilization” does not only mean that deliquescence and / or caking due to moisture absorption is prevented, but no occurrence of discoloration or off-flavor (bad odor) is observed. It means that there is no problem in use as an external preparation.
L-カルニチンL-酒石酸塩(LONZA社製)微粉砕物９２．０重量％、滑沢剤としてリョートーシュガーエステルS-370FUを２．０重量％、実施例として２種の、比較例として９種の賦形剤を６．０重量％秤量・篩過し、V型混合器にて10分間混合した後、混合末を透明２号NPハードカプセル(カプスゲル社製)に充填した。
充填カプセル5粒をポリエチレン製チャック袋に入れて高温高湿度下（40℃相対湿度75％）に保たれたインキュベーターに保管し、吸湿・潮解・劣化によって商品としての価値が失われるまでの日数を比較した。
ここに述べる「商品としての価値が失われるまでの日数」とは、吸湿による潮解及び／又は固結の発生、あるいは変色・異臭（悪臭）の発生によって、品質的に経口・外用剤としての使用に問題が認められることをいう。
また、充填カプセルをアルミ袋に密閉し、60℃のインキュベーターに保管し、1週間後の外観、臭いについて比較した。
さらに、各賦形剤のpH、嵩、比表面積、でんぷん分解物に関しては平均分子量を測定した。
実施例として、多孔質でんぷん分解物を、比較例として、多孔質の賦形剤あるいはでんぷん分解物、でんぷん、製剤化において頻繁に用いられる賦形剤を用い、カルニチンの吸湿性改善について評価した。
各試験例及び評価結果を表１に示す。
L-carnitine L-tartrate (manufactured by LONZA) 92.0% by weight finely pulverized product, 2.0% by weight of Ryoto Sugar Ester S-370FU as a lubricant, 2 types as examples, 9 as comparative examples The seed excipients were weighed and sieved to 6.0% by weight, mixed for 10 minutes in a V-type mixer, and the mixed powder was filled into a transparent No. 2 NP hard capsule (manufactured by Capsugel).
Put 5 filled capsules in a polyethylene zipper bag and store them in an incubator kept at high temperature and high humidity (40 ° C, relative humidity 75%) to determine the number of days until product value is lost due to moisture absorption, deliquescence, and deterioration. Compared.
“Days until product value is lost” as described here is used as an oral or external preparation in terms of quality due to the occurrence of deliquescence and / or solidification due to moisture absorption, or the occurrence of discoloration and off-flavor (odor). It means that there is a problem.
The filled capsules were sealed in an aluminum bag and stored in an incubator at 60 ° C., and the appearance and odor after one week were compared.
Furthermore, regarding the pH, bulk, specific surface area, and starch degradation product of each excipient, the average molecular weight was measured.
As an example, the improvement of carnitine hygroscopicity was evaluated using a porous starch degradation product as a comparative example, and using a porous excipient or starch degradation product, starch, and an excipient frequently used in formulation.
Each test example and evaluation results are shown in Table 1.
（結果）
ホタテ末や卵殻カルシウムは高い防湿性を付与するが、L-カルニチンL-酒石酸塩との反応によって気体を発生し、カプセルが外れてしまい、安定性が大きく損なわれた。
尚、油脂コートとしたカルニチンや、賦形剤と共に流動層造粒を実施したものについても検討したが、防湿効果はほとんど見られなかった。また、L-カルニチンL-酒石酸塩を粉砕せず結晶のまま用いても、微粉砕物と比べて潮解性・吸湿性にほとんど違いは見られなかった。
でんぷん、でんぷん分解物について種々検討したが、ｐHや嵩などの物性によって結果は大きく異なった。ほとんど効果の出ないもの、高い効果を示すものと様々であったが、検討の結果、pHが酸性付近、嵩0.3g/mL以下の多孔質デキストリン（製品名：パインフロー、パインフローＳ）が 最も安定性・防湿性を付与し、L-カルニチンL-酒石酸塩の高配合化と品質の向上を可能にすることを見出した。
尚、試験条件である40℃相対湿度75％、ポリエチレンチャック袋の条件は非常に苛酷であり、日本国内であれば年間通してこのような温湿度状態になることは考えにくい。実際、一般的な賦形剤であるセルロースでは本試験条件下における保存可能日数は３日であったが、この日数は、アルミチャック袋であれば、日本において高温多湿となる梅雨から夏場にかけての３〜４ヶ月間、商品価値を保てる日数に相当する。しかし、チャックの閉め忘れ、濡れた手での使用、アルミ包材の破損など、その使用条件によっては、数週間から１ヶ月くらいでくっつきや溶け・悪臭などが発生する恐れがある。従って、本試験条件のような苛酷な環境下において６日間の保存を可能にすることで、耐湿性の付与・安定性の向上など、より高い品質を担保できると考えられる。
(result)
Scallop powder and eggshell calcium provide high moisture resistance, but gas was generated by the reaction with L-carnitine L-tartrate, the capsule was removed, and the stability was greatly impaired.
In addition, although the carnitine used as the fat-and-oil coat and what carried out fluidized-bed granulation with the excipient | filler were examined, the moisture-proof effect was hardly seen. In addition, even when L-carnitine L-tartrate was used as a crystal without being pulverized, there was almost no difference in deliquescence and hygroscopicity compared to finely pulverized products.
Various studies were made on starch and starch degradation products, but the results differed greatly depending on physical properties such as pH and bulk. There were various types of products that showed little effect and high effect. However, as a result of investigation, porous dextrin (product name: Pine Flow, Pine Flow S) with a pH near acidity and a bulk of 0.3 g / mL or less was found. It has been found that the most stable and moisture-proof property can be imparted, and that L-carnitine L-tartrate can be highly formulated and the quality can be improved.
In addition, the conditions of 40 ° C. relative humidity 75% and polyethylene chuck bag, which are the test conditions, are very severe, and it is unlikely that such temperature and humidity conditions will occur throughout the year in Japan. In fact, cellulose, which is a common excipient, had a storage period of 3 days under the test conditions, but this number of days was from the hot and humid rainy season in Japan to the summer in the case of an aluminum chuck bag. This corresponds to the number of days for which the product value can be maintained for 3 to 4 months. However, depending on the conditions of use, such as forgetting to close the chuck, using it with wet hands, or damaging the aluminum packaging material, sticking, melting, or foul odor may occur within a few weeks to a month. Therefore, it is considered that higher quality such as imparting moisture resistance and improving stability can be secured by enabling storage for 6 days in a harsh environment such as this test condition.
Claims (2)
重量比率においてＬ−カルニチン若しくはＬ−カルニチンＬ−酒石酸塩：多孔質デキストリン＝８０〜９５：２０〜５であって、
前記多孔質デキストリンがデキストリンの粒子表面に微細孔を形成させた形状的な特徴を有するものであることを特徴とするカルニチン含有カプセル製剤。 L-carnitine or L-carnitine L-tartrate and porous dextrin ,
L-carnitine or L-carnitine L-tartrate: porous dextrin = 80-95: 20-5 in weight ratio,
A carnitine-containing capsule preparation characterized in that the porous dextrin has a shape characteristic in which micropores are formed on the particle surface of the dextrin .
重量比率においてＬ−カルニチン若しくはＬ−カルニチンＬ−酒石酸塩：多孔質デキストリン＝８０〜９５：２０〜５であって、
前記多孔質デキストリンがデンプンを酸又はアミラーゼで分解して得られる分解生成物を加熱したローラー上に乗せ、溶媒を蒸発させることにより得ることができるものであることを特徴とするカルニチン含有カプセル製剤。 L-carnitine or L-carnitine L-tartrate and porous dextrin,
L-carnitine or L-carnitine L-tartrate: porous dextrin = 80-95: 20-5 in weight ratio,
Carnitine-containing capsule formulation, characterized in that said porous dextrin is placed on a roller heated decomposition product obtained by decomposing the starch with acid or amylase, in which the solvent can be obtained by evaporation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008223559A JP5367328B2 (en) | 2008-09-01 | 2008-09-01 | Carnitine-containing preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008223559A JP5367328B2 (en) | 2008-09-01 | 2008-09-01 | Carnitine-containing preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010059060A JP2010059060A (en) | 2010-03-18 |
| JP5367328B2 true JP5367328B2 (en) | 2013-12-11 |
Family
ID=42186308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008223559A Active JP5367328B2 (en) | 2008-09-01 | 2008-09-01 | Carnitine-containing preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5367328B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7094816B2 (en) * | 2018-07-19 | 2022-07-04 | 株式会社ファンケル | Astaxanthin-containing powder |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61130219A (en) * | 1984-11-30 | 1986-06-18 | Dainippon Pharmaceut Co Ltd | Meclofenoxate hydrochloride composition |
| JPS61195200A (en) * | 1985-02-25 | 1986-08-29 | 株式会社資生堂 | Frame kneaded soap |
| JPH0783701B2 (en) * | 1987-07-23 | 1995-09-13 | 日本たばこ産業株式会社 | Tobacco flavor particles and method for producing the same |
| US5073376A (en) * | 1989-12-22 | 1991-12-17 | Lonza Ltd. | Preparations containing l-carnitine |
| JPH11313657A (en) * | 1998-05-08 | 1999-11-16 | Nof Corp | Granulation of hygroscopic powder and granulated material |
| JP2002287307A (en) * | 2001-03-23 | 2002-10-03 | Konica Corp | Solid processing agent for silver halide photographic sensitive material |
| WO2006028068A1 (en) * | 2004-09-08 | 2006-03-16 | Wako Pure Chemical Industries, Ltd. | Methods of purifying l-carnitine |
| JP5069416B2 (en) * | 2006-03-15 | 2012-11-07 | サントリーホールディングス株式会社 | Composition for food and drink with improved hygroscopicity |
-
2008
- 2008-09-01 JP JP2008223559A patent/JP5367328B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010059060A (en) | 2010-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6099870B2 (en) | Novel sweetener containing sucrose and D-psicose | |
| TWI418304B (en) | And hygroscopicity is improved | |
| JP6239579B2 (en) | Carnitine granules and method for producing the same | |
| KR20100044236A (en) | Amino-acid-containing medicinal granular preparation highly easy to take | |
| MX2015001930A (en) | Solid pharmaceutical preparation containing levothyroxine. | |
| JP2008280322A (en) | Bone strength improving agent | |
| JP2010189334A (en) | Acerola tablet | |
| JP2005002005A (en) | Coenzyme q10-containing composition | |
| JP5367328B2 (en) | Carnitine-containing preparation | |
| US7189416B2 (en) | Method for stable and controlled delivery of (-)-hydroxycitric acid | |
| KR20220077143A (en) | Reduced Volume Formulations Containing Amino Acid Entities | |
| JP5454142B2 (en) | Low-volume production method of solid preparation with high amino acid content | |
| JP6020813B2 (en) | Tablet granules and tablets | |
| JP2005104972A (en) | L-carnitine compression molded product and method for producing the same | |
| JP7030335B2 (en) | Oral composition | |
| JP5933383B2 (en) | Method for improving hygroscopicity / fluidity of solid preparation for internal use, solid preparation for internal use with improved hygroscopicity / flowability, and method for producing the solid preparation for internal use | |
| KR102549896B1 (en) | Capsule containing pyrroloquinolinequinone or a salt thereof and branched-chain amino acids | |
| JP7257715B2 (en) | oral composition | |
| JP6842970B2 (en) | Coenzyme Q10-containing preparation | |
| WO2015165492A1 (en) | Method for preparing an animal feed supplement composition | |
| JP6100939B2 (en) | Method for improving hygroscopicity / fluidity of solid preparation for internal use, solid preparation for internal use with improved hygroscopicity / flowability, and method for producing the solid preparation for internal use | |
| JP2023082066A (en) | oral composition | |
| ES2914650T3 (en) | choline butyrate salt | |
| JP2023049954A (en) | Packed product | |
| JP2006111550A (en) | Carnitine-containing product |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110513 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130312 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130513 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130611 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130730 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130910 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130911 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5367328 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |