JP2016505083A - 処理方法 - Google Patents
処理方法 Download PDFInfo
- Publication number
- JP2016505083A JP2016505083A JP2015553989A JP2015553989A JP2016505083A JP 2016505083 A JP2016505083 A JP 2016505083A JP 2015553989 A JP2015553989 A JP 2015553989A JP 2015553989 A JP2015553989 A JP 2015553989A JP 2016505083 A JP2016505083 A JP 2016505083A
- Authority
- JP
- Japan
- Prior art keywords
- extract
- pyrogen
- fucoidan
- surfactant
- polysaccharide
- 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.)
- Granted
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- 238000000034 method Methods 0.000 claims abstract description 81
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- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
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- SHPKCSFVQGSAJU-SEPHDYHBSA-L potassium fumarate Chemical compound [K+].[K+].[O-]C(=O)\C=C\C([O-])=O SHPKCSFVQGSAJU-SEPHDYHBSA-L 0.000 description 1
- 235000019295 potassium fumarate Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
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- 229940075579 propyl gallate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000004844 protein turnover Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
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- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
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- 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
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- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000008264 rhamnoses Chemical class 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 108700004121 sarkosyl Proteins 0.000 description 1
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- 108010078070 scavenger receptors Proteins 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- VFWRGKJLLYDFBY-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag].[Ag] VFWRGKJLLYDFBY-UHFFFAOYSA-N 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- PVGBHEUCHKGFQP-UHFFFAOYSA-N sodium;n-[5-amino-2-(4-aminophenyl)sulfonylphenyl]sulfonylacetamide Chemical compound [Na+].CC(=O)NS(=O)(=O)C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 PVGBHEUCHKGFQP-UHFFFAOYSA-N 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Biotechnology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Materials For Medical Uses (AREA)
Abstract
Description
本出願は、2013年1月25日に出願された米国仮特許出願第61/756,570号の利益を主張し、その明細書の内容は、参照によりその全体が本明細書に組み込まれる。
技術
本発明は、海藻などの海洋生物からの抽出物を処理するための方法に関する。より具体的には、本発明は、創傷管理および外科手術に使用するための非経口医薬組成物の製造に有用な、実質的に発熱因子を含まない抽出物の生成に関する。
[数1]
X=(Y−3.14)/−0.2
X=(3.212−3.14)/−0.2
X=−0.36
真数(−0.36)=0.44EU/mL(またはEU/mg)
出発材料は、天然炭水化物(約50%〜27.5%のフコース、22.5%のガラクトース)、硫酸塩(26%)、アセチル部分(3%)、および対イオン(8%)を含む、フコイダンに関して前に約87%に精製された凍結乾燥生成物であった。
フコイダン(15.00g)を300mLの蒸留水に溶解し、ガラスファイバフィルタを通して濾過した。蒸留水を用いて濾液を300gにした。40mLのフコイダン溶液のアリコートを、蒸留水で100mLに希釈し、0.2gのゼオライトを添加した。ガラスファイバフィルタを通して濾過する前に、懸濁液を14時間攪拌した。次いで、40mLの最終容量に濃縮し、凍結乾燥させる前に、濾液を、Amicon攪拌式セルを通して限外濾過し、保持液を100mLの蒸留水で洗浄した。
1%の発熱因子の減少(LALにより測定された)が見られた。
フコイダン(15.00g)を300mLの蒸留水に溶解し、ガラスファイバフィルタを通して濾過した。蒸留水を用いて濾液を300gにした。40mLのフコイダン溶液のアリコートを、0.5%のNaOHで100mLに希釈し、0.2gの活性炭を添加した。ガラスファイバフィルタを通して濾過する前に、懸濁液を14時間攪拌した。次いで、40mLの最終容量に濃縮し、凍結乾燥させる前に、濾液を、Amicon攪拌式セルを通して限外濾過し、保持液を100mLの発熱物質除去された蒸留水で洗浄した。66%の発熱因子の減少(LALにより測定された)が見られた。
フコイダン(10.00g)を、300mLの発熱物質除去された水に溶解した。ガラスファイバフィルタを通して溶液を濾過し、透明な褐色の溶液(約280mL)を得た。
フコイダン(6.00g)を、250mLの蒸留水に溶解した。0.5M NaOHを分配する自動滴定装置を使用して、pHを7.00に維持した。溶液を攪拌しながら、ホットプレート上で90℃に加熱し、次いで、3.0mLの30%w/w H2O2を添加した。1時間後、反応は4.37mLのアルカリを消費した。ガラスファイバフィルタを通して濾過する前に、溶液を一晩室温で放置した。次いで、50mLに濃縮し、凍結乾燥させる前に、濾液を、Amicon攪拌式セルを通して濾過し、保持液を50mLの発熱物質除去された蒸留水で洗浄した。
フコイダン(10.00g)を、250mLの蒸留水に溶解した。0.5M NaOHを分配する自動滴定装置を使用して、pHを7.00に維持した。溶液を攪拌しながら、ホットプレート上で60℃に加熱し、次いで、10.0mLの30%w/w H2O2および0.1gのクエン酸Felllを添加した。4時間後、14.92mLのアルカリが消費された。ガラスファイバフィルタを通して濾過する前に、溶液を一晩室温で放置した。次いで、50mLに濃縮し、凍結乾燥させる前に、濾液を、Amicon攪拌式セルを通して濾過し、保持液を50mLの発熱物質除去された蒸留水で洗浄した。
フコイダン(10.00g)を、250mLの蒸留水に溶解した。0.5M NaOHを分配する自動滴定装置を使用して、pHを7.00に維持した。溶液を攪拌しながら、ホットプレート上で60℃に加熱し、次いで、10.0mLの30%w/w H2O2および0.1gのクエン酸Felllを添加した。2時間後、12.10mLのアルカリが消費された。さらに5.0mLの30%w/w H2O2を添加した。10時間後、合計15.23mLのアルカリが消費された。ガラスファイバフィルタを通して濾過する前に、溶液を一晩室温で放置した。次いで、50mLに濃縮し、凍結乾燥させる前に、濾液を、Amicon攪拌式セルを通して限外濾過し、保持液を50mLの発熱物質除去された蒸留水で洗浄した。
フコイダン(10.00g)を、250mLの蒸留水に溶解した。0.5M NaOHを分配する自動滴定装置を使用して、pHを7.00に維持した。溶液を攪拌しながら、ホットプレート上で70℃に加熱し、次いで、10.0mLの30%w/w H2O2および0.1gのクエン酸Felllを添加した。1時間後、12.22mLのアルカリが消費された。ガラスファイバフィルタを通して濾過する前に、溶液を冷却し、一晩室温で放置した。Amicon攪拌式セルを通して限外濾過する前に、125mLの濾液のアリコートを、2.0gのTeric(登録商標)G12A12で1時間処理した。30mLに濃縮し、凍結乾燥させる前に、保持液を170mLの発熱物質除去された蒸留水で洗浄した。
フコイダン(2.00g)を、40℃に温めながら100mLの0.5M NaOHに溶解した。10分後、固体を遠心分離により分離し、破棄した。ガラスファイバフィルタを通して上清を濾過し、3時間、50mLのアリコートを60℃に加熱した。次いで、反応混合物を、発熱物質除去された蒸留水で100mLに希釈し、Amicon攪拌式セルを通して5mLの濃度に限外濾過した。次いで、保持液を75mLの発熱物質除去された蒸留水で洗浄し、5mLに濃縮し、凍結乾燥させた。
フコイダン(2.00g)を、40℃に温めながら100mLの0.5M NaOHに溶解した。10分後、固体を遠心分離により分離し、破棄した。ガラスファイバフィルタを通して上清を濾過し、50mLのアリコートを、3時間、60℃の1.00mLの30%w/w H2O2で処理した。次いで、反応混合物を、発熱物質除去された蒸留水で100mLに希釈し、Amicon攪拌式セルを通して5mLの濃度に限外濾過した。次いで、保持液を75mLの発熱物質除去された蒸留水で洗浄し、5mLに濃縮し、凍結乾燥させた。
フコイダン(8.00g)を、45℃に温めながら400mLの0.5M NaOHに溶解した。10分後、1時間、65℃の4.00mLの30%w/w H2O2で溶液を処理した。次いで、ガラスファイバフィルタを通して、反応混合物を濾過した。濾液のpHを、50% H2SO4で13.0から10.5に調節し、次いで、Amicon攪拌式セルを通して限外濾過し、20mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、20mLに再濃縮した。50mLの洗浄および再濃縮をさらに2回繰り返した。次いで、最終濃縮された保持液を凍結乾燥させた。
フコイダン(6.3g)を、45℃に温めながら300mLの0.5M NaOHに溶解した。反応混合物を65℃に加熱し、1時間、2.00mLの30%w/w H2O2で処理した。次いで、ガラスファイバフィルタを通して、反応混合物を濾過した。濾液のpHを、50% H2SO4で11.7から11.0に調節し、次いで、Amicon攪拌式セルを通して限外濾過し、20mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、20mLに再濃縮した。50mLの洗浄および再濃縮をさらに2回繰り返した。次いで、最終濃縮された保持液を凍結乾燥させた。
フコイダン(15.00g)を、40℃に温めながら735mLの0.5M NaOHに溶解した。反応混合物を遠心分離し、Dicalite濾過助剤を通して上清を濾過した。濾液を60℃に加熱し、30.0mLの30%w/w H2O2で1時間処理した。次いで、ガラスファイバフィルタを通して、pH10.0の反応混合物を濾過した。次いで、Amicon攪拌式セルを通して濾液を限外濾過し、30mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、30mLに再濃縮した。50mLの洗浄および再濃縮をさらに2回繰り返した。次いで、最終濃縮された保持液を凍結乾燥させた。
フコイダン(4.0g)を、40℃に温めながら200mLの0.5M NaOHに溶解した。反応混合物を遠心分離し、Dicalite濾過助剤を通して上清を濾過した。濾液を60℃に加熱し、5.0mLの30%w/w H2O2で30分間処理した。次いで、ガラスファイバフィルタを通して、pH10.7の反応混合物を濾過した。次いで、Amicon攪拌式セルを通して濾液を限外濾過し、30mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、30mLに再濃縮した。50mLの洗浄および再濃縮をさらに2回繰り返した。次いで、最終濃縮された保持液を凍結乾燥させた。
フコイダン(4.0g)を、40℃に温めながら200mLの0.5M NaOHに溶解した。反応混合物を遠心分離し、Dicalite濾過助剤を通して上清を濾過した。濾液を60℃に加熱し、2.0mLの30%w/w H2O2で30分間処理した。次いで、ガラスファイバフィルタを通して、pH10.7の反応混合物を濾過した。次いで、Amicon攪拌式セルを通して濾液を限外濾過し、30mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、30mLに再濃縮した。50mLの洗浄および再濃縮をさらに2回繰り返した。次いで、最終濃縮された保持液を凍結乾燥させた。
フコイダン(4.0g)を、40℃に温めながら200mLの0.5M NaOHに溶解した。反応混合物を遠心分離し、Dicalite濾過助剤を通して上清を濾過した。濾液を70℃に加熱し、0.7mLの30%w/w H2O2で30分間処理した。次いで、ガラスファイバフィルタを通して、反応混合物を濾過した。次いで、Amicon攪拌式セルを通して濾液を限外濾過し、30mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、30mLに再濃縮した。50mLの洗浄および再濃縮をさらに2回繰り返した。次いで、最終濃縮された保持液を凍結乾燥させた。
フコイダン(2.0g)を、40℃に温めながら200mLの0.5M NaOHに溶解した。次いで、反応混合物を65℃に加熱し、1.0mLの30%w/w H2O2で30分間処理した。次いで、ガラスファイバフィルタを通して、反応混合物を濾過した。次いで、Amicon攪拌式セルを通して濾液を限外濾過し、30mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、30mLに再濃縮した。50mLの洗浄および再濃縮をさらに2回繰り返した。次いで、最終濃縮された保持液を凍結乾燥させた。
フコイダン(4.0g)を、40℃に温めながら200mLの0.5M NaOHに溶解した。反応混合物を遠心分離し、dicalite濾過助剤を通して上清を濾過した。濾液を65℃に加熱し、2.0mLの30%w/w H2O2で30分間処理した。次いで、ガラスファイバフィルタを通して、反応混合物を濾過した。次いで、Amicon攪拌式セルを通して濾液を限外濾過し、30mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、30mLに再濃縮した。50mLの洗浄および再濃縮をさらに2回繰り返した。次いで、最終濃縮された保持液を凍結乾燥させた。
ウルバン(2.0g)を、55℃に温めながら150mLの0.5M KOHに溶解した。濾液を65℃に加熱し、6.0mLの30%w/w H2O2で60分間処理した。次いで、反応混合物を50% H2SO4でpH12.1からpH7.8に中和した。次いで、Amicon攪拌式セルを通して濾液を限外濾過し、30mLの容量に濃縮した。次いで、保持液を50mLの発熱物質除去された蒸留水で洗浄し、30mLに再濃縮した。50mLの洗浄および再濃縮をさらに3回繰り返した。次いで、0.2μmのフィルタを通して最終濃縮保持液を濾過し、凍結乾燥させた。
出発材料は、天然炭水化物(約60.1%〜54.0%のフコース、3.0%のガラクトース)、硫酸塩(27.5%)、および対イオン(7.5%)を含む、フコイダンに関して前に約95%に精製された.凍結乾燥生成物であった。
50℃に温めながら、フコイダン(50g)を、2Lの1%w/w H2SO4に溶解した。この温度で反応混合物を1時間攪拌した。50%w/w NaOHを添加することにより、溶液のpHを1.2から4.0に上げた。
海藻(5.0g、ワカメ)を、前に55℃に加熱された100gの0.5%w/w H2SO4に懸濁した。得られたpH1.8の懸濁液を、50℃で4時間攪拌し、次いで、珪藻土で覆われたセルロースフィルタを通して濾過した。次いで、10%w/w NaOHを用いて濾液のpHを11.0に上げ、攪拌しながら溶液を45℃に加熱した。この溶液に、0.5mLの30%w/w H2O2を添加し、10%w/w NaOHを添加することにより、溶液のpHをpH10.9超に維持した。1時間後、溶液を加熱から取り外し、10%w/w H2SO4でpHを5.01に下げた。次いで、50mLに濃縮し、凍結乾燥させる前に、冷却した溶液を、Amicon攪拌式セルを通して濾過し、保持液を50mLの発熱物質除去された蒸留水で3回洗浄した。精製された白色のフコイダンの10.8%の単離された収率を得た。
Claims (28)
- 標的分子および発熱物質を含む海藻抽出物を処理する方法であって、前記発熱物質を不活性化するステップ、および/または前記発熱物質を除去するステップを含み、前記抽出物の発熱性の減少をもたらす、方法。
- 前記抽出物を有効量の以下:酸化剤、界面活性剤、塩基、活性炭、ゼオライトのうちの1つ以上と接触させることを含む、請求項1に記載の方法。
- 前記酸化剤が、過酸化物である、請求項2に記載の方法。
- 前記過酸化物が、少なくとも約30%(w/w、過酸化物の質量対多糖類の質量に基づく)の量で使用される、請求項3に記載の方法。
- 前記界面活性剤が、生物系界面活性剤である、請求項2〜4のいずれか一項に記載の方法。
- 前記界面活性剤が、非イオン性界面活性剤である、請求項2〜5のいずれか一項に記載の方法。
- 前記界面活性剤が、少なくとも約50%(w/w、界面活性剤の質量対多糖類の質量に基づく)の量で使用される、請求項2〜6のいずれか一項に記載の方法。
- 前記塩基が、約7.0超かつ約12.5未満のpHをもたらすのに十分な量で使用される、請求項2〜6のいずれか一項に記載の方法。
- 前記活性炭またはゼオライトが、少なくとも約10%(w/w、吸着剤の質量対多糖類の質量)の量で使用される、請求項2〜8のいずれか一項に記載の方法。
- 前記抽出物を有効量の酸化剤および塩基と接触させることを含む、請求項1〜9のいずれか一項に記載の方法。
- 前記抽出物を有効量の酸化剤、塩基、および界面活性剤と接触させることを含む、請求項1〜9のいずれか一項に記載の方法。
- 前記抽出物を有効量の活性炭および塩基と接触させることを含む、請求項1〜9のいずれか一項に記載の方法。
- 多糖類に対する回収率が、少なくとも約30%である、請求項1〜12のいずれか一項に記載の方法。
- 多糖類に対する回収率が、少なくとも約60%である、請求項1〜12のいずれか一項に記載の方法。
- 少なくとも約50%の発熱物質が除去され、かつ/または不活性化される、請求項1〜14のいずれか一項に記載の方法。
- 少なくとも約99%の発熱物質が除去され、かつ/または不活性化される、請求項1〜14のいずれか一項に記載の方法。
- 前記標的分子が、多糖類である、請求項1〜16のいずれか一項に記載の方法。
- 前記多糖類が、硫酸化多糖類、任意にフコイダンまたはウルバンである、請求項17に記載の方法。
- 請求項1〜18のいずれか一項に記載の方法によって生成される抽出物。
- 実質的に発熱物質除去された(depyrogenated)海洋生物の抽出物。
- LALにより決定するとき、約100EU/mg未満の発熱物質レベルを有する、請求項20に記載の抽出物。
- ウサギ発熱性試験に合格できる請求項20に記載の抽出物。
- 請求項1〜18のいずれか一項に記載の方法によって生成される、請求項20〜22のいずれか一項に記載の抽出物。
- 薬剤的に許容される賦形剤と組み合わせて、請求項19〜23のいずれか一項に記載の抽出物を含む、医薬組成物。
- 請求項19〜23のいずれか一項に記載の抽出物を含む生体材料。
- 病態の治療または予防を必要とする哺乳類に、請求項24に記載の医薬組成物を投与すること、または請求項25に記載の生体材料を移植することを含む、病態を治療する、または予防するための方法。
- 医薬品における、請求項24に記載の医薬組成物、または請求項25に記載の生体材料、または請求項19〜23のいずれか一項に記載の抽出物の使用。
- 病態を治療または予防するための薬剤の製造における、請求項19〜23のいずれか一項に記載の抽出物、または請求項25に記載の生体材料、または請求項24に記載の医薬組成物の使用。
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JP2021532137A (ja) * | 2018-07-27 | 2021-11-25 | エーアールシー メディカル デバイス,インク. | 低エンドトキシンフカン組成物、システム及び方法 |
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JP2022177054A (ja) * | 2018-07-27 | 2022-11-30 | エーアールシー メディカル デバイス,インク. | 低エンドトキシンフカン組成物、システム及び方法 |
JP2022177065A (ja) * | 2018-07-27 | 2022-11-30 | エーアールシー メディカル デバイス,インク. | 線維性癒着の処置のための高度に精製され且つ/又は改変されたフカン組成物 |
US11628183B2 (en) | 2018-07-27 | 2023-04-18 | ARC Medical Ine. | Highly purified fucans for the treatment of fibrous adhesions |
US11642368B2 (en) | 2018-07-27 | 2023-05-09 | ARC Medical Inc. | Highly purified and/or modified fucan compositions for the treatment of fibrous adhesions |
JP7302831B2 (ja) | 2018-07-27 | 2023-07-04 | エーアールシー メディカル デバイス,インク. | 低エンドトキシンフカン組成物、システム及び方法 |
US11938145B2 (en) | 2018-07-27 | 2024-03-26 | ARC Medical Inc. | Low endotoxin fucan compositions, systems, and methods |
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AU2013375786A1 (en) | 2015-08-20 |
CN105101982A (zh) | 2015-11-25 |
US20150359828A1 (en) | 2015-12-17 |
NZ710602A (en) | 2020-01-31 |
EP2948158B1 (en) | 2017-09-06 |
CA2898515C (en) | 2022-01-04 |
JP6336487B2 (ja) | 2018-06-06 |
EP2948158A1 (en) | 2015-12-02 |
CA2898515A1 (en) | 2014-07-31 |
EP2948158A4 (en) | 2016-07-20 |
RU2686088C2 (ru) | 2019-04-24 |
WO2014113836A1 (en) | 2014-07-31 |
KR102223725B1 (ko) | 2021-03-08 |
RU2015135635A (ru) | 2017-03-03 |
AU2013375786B2 (en) | 2018-10-04 |
US10149874B2 (en) | 2018-12-11 |
HK1215164A1 (zh) | 2016-08-19 |
DK2948158T3 (en) | 2017-10-02 |
KR20150108919A (ko) | 2015-09-30 |
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