JP2018027956A - 安定化スルフォラファン - Google Patents
安定化スルフォラファン Download PDFInfo
- Publication number
- JP2018027956A JP2018027956A JP2017173723A JP2017173723A JP2018027956A JP 2018027956 A JP2018027956 A JP 2018027956A JP 2017173723 A JP2017173723 A JP 2017173723A JP 2017173723 A JP2017173723 A JP 2017173723A JP 2018027956 A JP2018027956 A JP 2018027956A
- Authority
- JP
- Japan
- Prior art keywords
- cyclodextrin
- sulforaphane
- complex
- isothiocyanato
- solution
- 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
Links
- SUVMJBTUFCVSAD-UHFFFAOYSA-N sulforaphane Chemical compound CS(=O)CCCCN=C=S SUVMJBTUFCVSAD-UHFFFAOYSA-N 0.000 title claims abstract description 238
- 235000015487 sulforaphane Nutrition 0.000 title claims abstract description 121
- SUVMJBTUFCVSAD-JTQLQIEISA-N 4-Methylsulfinylbutyl isothiocyanate Natural products C[S@](=O)CCCCN=C=S SUVMJBTUFCVSAD-JTQLQIEISA-N 0.000 title claims abstract description 113
- 229960005559 sulforaphane Drugs 0.000 title claims abstract description 113
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 150
- 239000000203 mixture Substances 0.000 claims abstract description 117
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 91
- 238000000034 method Methods 0.000 claims abstract description 81
- 239000002904 solvent Substances 0.000 claims abstract description 56
- 239000000725 suspension Substances 0.000 claims abstract description 49
- 239000007787 solid Substances 0.000 claims abstract description 26
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims abstract description 10
- 230000000087 stabilizing effect Effects 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 17
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
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- BQYLCVLIDSFGNX-UHFFFAOYSA-N 6-isothiocyanatohexan-2-ol Chemical compound CC(O)CCCCN=C=S BQYLCVLIDSFGNX-UHFFFAOYSA-N 0.000 claims description 6
- KXJVOLXLYNDZME-UHFFFAOYSA-N 6-isothiocyanatohexan-2-one Chemical compound CC(=O)CCCCN=C=S KXJVOLXLYNDZME-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 6
- 235000011187 glycerol Nutrition 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 6
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- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- QZRFYFSUCVLHML-IUCAKERBSA-N (1s,3s)-1-(isothiocyanatomethyl)-3-methylsulfonylcyclohexane Chemical compound CS(=O)(=O)[C@H]1CCC[C@H](CN=C=S)C1 QZRFYFSUCVLHML-IUCAKERBSA-N 0.000 claims description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
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- 238000007918 intramuscular administration Methods 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
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- 238000001990 intravenous administration Methods 0.000 claims description 4
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- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- SIQPZGADPPVYAP-UHFFFAOYSA-N 1-isothiocyanato-5-methylsulfonylpentane Chemical compound CS(=O)(=O)CCCCCN=C=S SIQPZGADPPVYAP-UHFFFAOYSA-N 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 claims description 3
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 claims description 3
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
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- WUKNJNKEEVSNKV-UHFFFAOYSA-N 1-sulfonylpentane Chemical compound CCCCC=S(=O)=O WUKNJNKEEVSNKV-UHFFFAOYSA-N 0.000 claims 2
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- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
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- 150000008501 α-D-glucopyranosides Chemical group 0.000 description 1
Images
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Abstract
【解決手段】スルフォラファン又はその類似体をシクロデキストリンに接触させてスルフォラファン又はその類似体とシクロデキストリンとの複合体を形成させる安定化方法。シクロデキストリンが、W6(α)シクロデキストリン、W7(β)シクロデキストリ、W8(γ)シクロデキストリン及びそれらの混合物から選択されることが好ましい、安定化方法。シクロデキストリンを溶媒又は溶媒混合液に溶解又は懸濁させて、溶液又は懸濁液とし、更にそこにスルフォランファン又はその類似体を溶解又は懸濁させて、複合体を形成し、溶液又は懸濁液から、形成した複合体を懸濁液から固体を分離するか、溶液から複合体を沈殿させて固体を分離する、方法。
【選択図】図1
Description
カリウムフタルイミド(65g,350mmol,1.00当量)およびテトラメチレンジブロミド(200g,930mmol,2.66当量)を合せて(非希釈で)、12時間加熱した。余剰のテトラメチレンジブロミドを回転蒸発(回転気化器)によって除去した。得られた残渣をエタノールで消化し、濾過した。静置中に結晶化した材料を濾過し、エタノールで洗浄し、真空下で乾燥した。濾液と洗浄液とを集めて濃縮すると第二のクロップが得られた。クロップの合計重量は60.5g(収率61%)であった。
中間体B:
すべてのガラス器具類を乾燥した(N2流/加熱ガン)。撹拌棒を備えた2L容の丸底フラスコに、300mLの無水メタノールを充填した。ナトリウム(6.48g,281.8mmol,1.06当量)を慎重に添加した。室温で、メチルメルカプタン(MeSH,13.56g,281.8mmol,1.06当量)をシリンジから一回で充填した。[MeSH(気体状)はドライアイス/アセトン低温フィンガートラップを備えたドライアイス/アセトン浴に入れた別の多口丸底フラスコにトラップし、ドライ/フリーザー冷却シリンジに移した。]ブロモブチルフタルイミド(75.0g,265.8mmol,1.00当量)を300mLの無水メタノールに懸濁させ、反応混合物に加えた。反応混合物を窒素下に室温で一夜撹拌した。反応混合物のアリコートをガスクロマトグラフィーで分析して反応完了を確認した。次に、300mLの水を反応混合物に添加し、回転気化器で蒸留してアルコールを除去すると、この時点で生成物が溶液から沈殿した。生成物(白色固体)を濾別し、2×150mlの冷水で洗浄した。生成物を40℃の真空オーブンに入れて一夜乾燥すると、65.2g(98%収率)の白色固体が得られ、ガスクロマトグラフィーによればこれは98.4%の純度を示した。生成物を窒素下で保存した。
中間体B(45.0g,180.5mmol,1.00当量)を580mLの酢酸とエタノールとの1:1混合物に懸濁させた(完全溶解しない)。懸濁液を氷/ブライン浴で冷却した。過酸化水素溶液(120.014 M AQ、予め滴定、15.02mL,180.5mmol,1.00当量)を添加し、反応混合物を室温に加温して一夜撹拌した。処理中に材料が溶解し、淡黄色溶液となった。アリコートを薄層クロマトグラフィー(非希釈のEtOAc)によって点検して反応完了を確認した。反応混合物を回転気化器で濃縮し(不完全、溶媒の〜90%を除去)、400mLのメチルtert−ブチルエーテル(MTBE)で希釈すると、この時点で生成物(淡黄色固体)が溶液から沈殿した。固体を濾別し、追加量の100mLのMTBEで洗浄した。MTBE濾液から第二クロップを収集した。双方のクロップの合計重量は44.5g(収率95%)であり、HPLC純度は〜95%であった。NMRは残留酢酸を示した。材料をそれ以上精製しなかった。
撹拌棒を備えた500mL容の丸底フラスコを乾燥し(N2流/加熱ガン)、中間体C(35.34g,133.19mmol,1.0当量)を充填した。メチルアミン(エタノール中の33wt%溶液,175mmL,〜10当量)を丸底フラスコに充填した。固体中間体Cは約45分でゆっくりと溶液に取込まれた。さらに1時間後、溶液から固体が沈殿し始めた(メチルフタルイミドと推定される)。反応混合物を十分に密封して室温で一夜撹拌した。反応混合物を50mLのエタノールで希釈し(固体がある程度溶解)、濾過して、メチルフタルイミド副生物を除去した。固体副生物を追加量の2×25mLのエタノールで洗浄した。濾液を回転気化器(浴温度約30℃未満)で洗浄した。残渣を50gのシリカに吸着させ、50gのシリカでカラムにかけた。残留メチルフタルイミド副生物の洗浄には3カラムボリュームのジクロロメタンで十分であった。ジクロロメタン中の40%の9:1のメタノール:水酸化アンモニウムを使用して生成物を溶出した。19.1gの淡黄色油が得られた。これはGCによって純粋であったが水を含有しており、NMRによって水酸化アンモニウムが収集された。油を1ミリバールおよび185℃の空気浴温度でクーゲルロール(kuglrhor)蒸留すると、11.80gの黄色油が得られた(収率65.5%)。これはGCで99%を上回る純度を有していた。ポット残渣は3.14gと計量され、熱分解があり得ることを示す。
撹拌棒を備えた1L容の丸底フラスコに、中間体D(10.8g,79.9mmol,1.00当量)、300mLのクロロホルムおよび133mLの1NのNaOH(水性)溶液(132.8mmol,1.66当量)を充填した。2相溶液に、チオホスゲン(13.78g,119.8mmol,1.50当量)を充填した。反応混合物を1時間激しく撹拌した後、アリコートを薄層クロマトグラフィーによって点検した。混合物を〜300mLのクロロホルムおよび200mLのブラインで希釈した。有機相を除去し、水相を2×500mLのクロロホルムで再度抽出した。有機相を集めて、硫酸ナトリウムで乾燥し、濃縮した。残渣を20gのシリカに吸着させ、50gのシリカでカラムにかけ、クロロホルム中の0から4%のメタノールで溶出させた。12.14g(収率85.7%)の所望生成物を淡黄色油として収集した。
スルフォラファンを3種類のシクロデキストリン:W6(アルフア)、W7(ベータ)およびW8(ガンマ)に配合した。これらのシクロデキストリンはWacker Chemie AG(CAVAMAXTMブランド、食品グレードまたは医薬グレード)から購入した。
分析の概説:内部標準(DEET)法を使用するHPLC(254nmでUV検出)によってスルフォラファン配合物を分析した。クロマトグラフィー条件下でスルフォラファンがシクロデキストリンから完全に解離すると想定する。スルフォラファン標準(フリーザーに保存)を使用して各分析の応答率を決定する。初期試験で、この標準の濃度に対する応答の直線性が証明された。すべての分析において、注入したすべての標準の応答率(RF)は安定に維持されたので、フリーザー内の標準の安定性が証明された。
カラム:Agilent Eclipse XDB−C18,5μm,250×4.6mm,30℃
溶媒A:水中の0.1%ギ酸
溶媒B:MeCN
勾配:30分間で溶媒A中に5%から100%の溶媒B
流速:1.5mL/分
デテクタ:UV254nm,ESI−MS(pos/neg),確認用
保持時間:スルフォラファン:9.2分,DEET:15.5分。
約300mg(慎重に計量)の配合物サンプルを8mLの内部標準溶液(DMF中のDEET、約2mg/mL)に溶解した。ISTD溶液の量も慎重に計量した。窒素を吹込んだ8mLの脱イオン水でサンプルをさらに希釈した。サンプルを〜10分間超音波処理し、0.45μmのナイロンフイルターで濾過した。次に254nmでUV検出するHPLCによってサンプルを分析した。
カラム:Agilent Eclipse XDB−C18,5μm,250×4.6mm,30℃
溶媒A:H2O中の0.1%ギ酸
溶媒B:MeCN
勾配:30分間で溶媒A中に5%から100%の溶媒B
流速:1.5mL/分
デテクタ:UV254nm,ESI−MS(pos/neg),確認用
保持時間:スルフォラファン:9.2分,DEET:15.5分。
Claims (37)
- スルフォラファンまたはその類似体を少なくとも1種のシクロデキストリンに接触させてスルフォラファンまたはその類似体と少なくとも1種のシクロデキストリンとの複合体を形成させる段階を含むスルフォラファンまたはその類似体の安定化方法。
- 少なくとも1種のシクロデキストリンが、W6(アルフア)シクロデキストリン、W7(ベータ)シクロデキストリン、W8(ガンマ)シクロデキストリンおよびそれらの混合物から成るグループから選択される請求項1に記載の方法。
- スルフォラファンの類似体が、6−イソチオシアナト−2−ヘキサノン、エキソ−2−アセチル−6−イソチオシアナトノルボルナン、エキソ−2−イソチオシアナト−6−メチルスルホニルノルボルナン、6−イソチオシアナト−2−ヘキサノール、1−イソチオシアナト−4−ジメチルホスホニルブタン、エキソ−2−(1’−ヒドロキシエチル)−5−イソチオシアナトノルボルナン、エキソ−2−アセチル−5−イソチオシアナトノルボルナン、1−イソチオシアナト−5−メチルスルホニルペンタンおよびシス−またはトランス−3−(メチルスルホニル)シクロヘキシルメチルイソチオシアナートおよびそれらの混合物から成るグループから選択される請求項1に記載の方法。
- スルフォラファンまたはその類似体を少なくとも1種のシクロデキストリンに接触させる段階が、
少なくとも1種のシクロデキストリンを溶媒または溶媒混合物に溶解または懸濁させて溶液または懸濁液を形成する段階と、
スルフォラファンまたはその類似体を前記溶液または懸濁液に溶解または懸濁させる段階と、
を含む請求項1に記載の方法。 - 溶媒が、水、メタノール、エタノール、n−プロパノール、イソ−プロパノール、n−ブタノール、sec−ブタノール、イソ−ブタノール、tert−ブタノール、高分子量アルコール、ジメチルホルムアミド、ジエチルホルムアミド、エチレングリコール、トリエチレングリコール、グリセリン、ポリエチレングリコール、ギ酸、酢酸、ホルムアミド、アセトン、テトラヒドロフラン、ジオキサン、メチルエチルケトン、高分子量ケトン、酢酸エチル、アセトニトリル、N,N−ジメチルアセトアミド、ジメチルスルホキシド、二硫化炭素、ヘキサン、ヘキサン異性体、シクロヘキサン、ヘプタン、ヘプタン異性体、C8−C16溶媒、鉱油、ジエチルエーテル、メチルtert−ブチルエーテル、メチレンクロリド、クロロホルム、四塩化炭素、ベンゼン、ニトロベンゼン、トルエンおよびそれらの混合物から成るグループから選択される請求項4に記載の方法。
- さらに、溶液または懸濁液から複合体を分離する段階を含む請求項4に記載の方法。
- 溶液または懸濁液から複合体を分離する段階が、懸濁液から固体を単離するか、または、溶液から複合体を沈殿させ、得られた固体を次いで単離する段階を含む請求項6に記載の方法。
- 溶液または懸濁液から複合体を分離する段階が、1種以上の溶媒から蒸発または部分蒸発させ、得られた固体を次いで単離する段階を含む請求項6に記載の方法。
- 溶液または懸濁液から複合体を分離する段階が、1種以上の溶媒をシクロデキストリンで飽和して1種以上の溶媒中の複合体の溶解度を低下させる段階を含む請求項6に記載の方法。
- スルフォラファンまたはその類似体を少なくとも1種のシクロデキストリンに接触させる段階が、
スルフォラファンまたはその類似体を溶媒または溶媒混合物に溶解または懸濁させて溶液または懸濁液を形成する段階と、
少なくとも1種のシクロデキストリンを前記溶液または懸濁液に溶解または懸濁させる段階と、
を含む請求項1に記載の方法。 - 溶媒が、水、メタノール、エタノール、n−プロパノール、イソ−プロパノール、n−ブタノール、sec−ブタノール、イソ−ブタノール、tert−ブタノール、高分子量アルコール、ジメチルホルムアミド、ジエチルホルムアミド、エチレングリコール、トリエチレングリコール、グリセリン、ポリエチレングリコール、ギ酸、酢酸、ホルムアミド、アセトン、テトラヒドロフラン、ジオキサン、メチルエチルケトン、高分子量ケトン、酢酸エチル、アセトニトリル、N,N−ジメチルアセトアミド、ジメチルスルホキシド、二硫化炭素、ヘキサン、ヘキサン異性体、シクロヘキサン、ヘプタン、ヘプタン異性体、C8−C16溶媒、鉱油、ジエチルエーテル、メチルtert−ブチルエーテル、メチレンクロリド、クロロホルム、四塩化炭素、ベンゼン、ニトロベンゼン、トルエンおよびそれらの混合物から成るグループから選択される請求項10に記載の方法。
- さらに、溶液または懸濁液から複合体を分離する段階を含む請求項10に記載の方法。
- 溶液または懸濁液から複合体を分離する段階が、懸濁液から固体を単離するか、または、溶液から複合体を沈殿させ、得られた固体を次いで単離する段階を含む請求項12に記載の方法。
- 溶液または懸濁液から複合体を分離する段階が、1種以上の溶媒から蒸発または部分蒸発させ、得られた固体を次いで単離する段階を含む請求項12に記載の方法。
- 溶液または懸濁液から複合体を分離する段階が、1種以上の溶媒をシクロデキストリンで飽和して1種以上の溶媒中の複合体の溶解度を低下させる段階を含む請求項12に記載の方法。
- スルフォラファンまたはその類似体とシクロデキストリンとの複合体を形成する段階を室温で行う請求項1に記載の方法。
- スルフォラファンまたはその類似体とシクロデキストリンとの複合体を形成する段階を室温よりも高い温度で行う請求項1に記載の方法。
- スルフォラファンまたはその類似体とシクロデキストリンとの複合体を形成する段階を室温よりも低い温度で行う請求項1に記載の方法。
- スルフォラファンまたはその類似体を少なくとも1種のシクロデキストリンに接触させてシクロデキストリンとの複合体を形成させる段階が、複合体中のシクロデキストリンに対するスルフォラファンの配合重量が約0.01重量%から約30重量%になるために十分な量のスルフォラファンをシクロデキストリンに接触させる段階を含む請求項1に記載の方法。
- スルフォラファンまたはその類似体を少なくとも1種のシクロデキストリンに接触させる段階が、
少なくとも1種のシクロデキストリンを溶媒または溶媒混合物に溶解または懸濁させて第一溶液または懸濁液を形成する段階と、
スルフォラファンまたはその類似体を同じまたは異なる溶媒または溶媒混合物に溶解または懸濁させて第二溶液または懸濁液を形成する段階と、
第一溶液または懸濁液を第二溶液または懸濁液に合せる段階と、
を含む請求項1に記載の方法。 - スルフォラファンとシクロデキストリンとの複合体を含む組成物。
- 前記シクロデキストリンが、W6(アルフア)シクロデキストリン、W7(ベータ)シクロデキストリン、W8(ガンマ)シクロデキストリンおよびそれらの混合物から成るグループから選択される請求項21に記載の組成物。
- スルフォラファン類似体とシクロデキストリンとの複合体を含む組成物。
- 前記スルフォラファン類似体が、6−イソチオシアナト−2−ヘキサノン、エキソ−2−アセチル−6−イソチオシアナトノルボルナン、エキソ−2−イソチオシアナト−6−メチルスルホニルノルボルナン、6−イソチオシアナト−2−ヘキサノール、1−イソチオシアナト−4−ジメチルホスホニルブタン、エキソ−2−(1’−ヒドロキシエチル)−5−イソチオシアナトノルボルナン(isothiocyanatonorborane)、エキソ−2−アセチル−5−イソチオシアナトノルボルナン、1−イソチオシアナト−5−メチルスルホニルペンタンおよびシス−またはトランス−3−(メチルスルホニル)シクロヘキシルメチルイソチオシアナートおよびそれらの混合物から成るグループから選択される請求項23に記載の組成物。
- 前記シクロデキストリンが、W6(アルフア)シクロデキストリン、W7(ベータ)シクロデキストリン、W8(ガンマ)シクロデキストリンおよびそれらの混合物から成るグループから選択される請求項23に記載の組成物。
- シクロデキストリンとスルフォラファンまたはその類似体との複合体と賦形剤とを含む医薬組成物。
- 前記シクロデキストリンが、W6(アルフア)シクロデキストリン、W7(ベータ)シクロデキストリン、W8(ガンマ)シクロデキストリンおよびそれらの混合物から成るグループから選択される請求項26に記載の組成物。
- 前記スルフォラファンまたはスルフォラファン類似体が、6−イソチオシアナト−2−ヘキサノン、エキソ−2−アセチル−6−イソチオシアナトノルボルナン、エキソ−2−イソチオシアナト−6−メチルスルホニルノルボルナン、6−イソチオシアナト−2−ヘキサノール、1−イソチオシアナト−4−ジメチルホスホニルブタン、エキソ−2−(1’−ヒドロキシエチル)−5−イソチオシアナトノルボルナン、エキソ−2−アセチル−5−イソチオシアナトノルボルナン、1−イソチオシアナト−5−メチルスルホニルペンタンおよびシス−またはトランス−3−(メチルスルホニル)シクロヘキシルメチルイソチオシアナートおよびそれらの混合物から成るグループから選択される請求項26に記載の組成物。
- 組成物が、経口、外用、非経口、注射、口腔内、舌下、筋肉内または静脈内投与の1つ以上で投与される請求項26に記載の組成物。
- 経口剤形が食物サプリメント、食品、食品サプリメントまたは食品添加物の1つ以上である請求項29に記載の組成物。
- 外用剤形がクリーム、ゼリー、軟膏または懸濁液の1つ以上である請求項29に記載の組成物。
- シクロデキストリンとスルフォラファンまたはその類似体との複合体と賦形剤とを含む機能性食品組成物。
- 前記シクロデキストリンが、W6(アルフア)シクロデキストリン、W7(ベータ)シクロデキストリン、W8(ガンマ)シクロデキストリンおよびそれらの混合物から成るグループから選択される請求項32に記載の組成物。
- 前記スルフォラファンまたはスルフォラファンの類似体が、6−イソチオシアナト−2−ヘキサノン、エキソ−2−アセチル−6−イソチオシアナトノルボルナン、エキソ−2−イソチオシアナト−6−メチルスルホニルノルボルナン、6−イソチオシアナト−2−ヘキサノール、1−イソチオシアナト−4−ジメチルホスホニルブタン、エキソ−2−(1’−ヒドロキシエチル)−5−イソチオシアナトノルボルナン、エキソ−2−アセチル−5−イソチオシアナトノルボルナン、1−イソチオシアナト−5−メチルスルホニルペンタンおよびシス−またはトランス−3−(メチルスルホニル)シクロヘキシルメチルイソチオシアナートおよびそれらの混合物から成るグループから選択される請求項32に記載の組成物。
- 組成物が、経口、外用、非経口、注射、口腔内、舌下、筋肉内または静脈内投与の1つ以上で投与される請求項32に記載の組成物。
- 経口剤形が食物サプリメント、食品、食品サプリメントまたは食品添加物の1つ以上である請求項35に記載の組成物。
- 外用剤形がクリーム、ゼリー、軟膏または懸濁液の1つ以上である請求項35に記載の組成物。
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JP (4) | JP2010516766A (ja) |
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HK (2) | HK1199407A1 (ja) |
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LT (1) | LT3354267T (ja) |
PL (2) | PL2796140T3 (ja) |
PT (1) | PT3354267T (ja) |
SI (1) | SI3354267T1 (ja) |
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Families Citing this family (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2672971C (en) * | 2007-01-23 | 2014-03-11 | Pharmagra Labs, Inc. | Stabilized sulforaphane |
WO2010065329A2 (en) * | 2008-11-25 | 2010-06-10 | The Board Of Regents Of The University Of Texas System | Nanoparticles for cancer treatment |
BE1019434A3 (fr) * | 2010-07-23 | 2012-07-03 | Auriga Internat | Stabilisation du sulforaphane. |
US10647668B2 (en) | 2011-01-03 | 2020-05-12 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactant and associated method of use |
US10308599B2 (en) | 2011-01-03 | 2019-06-04 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactants, formulations incorporating the same, and associated methods of use |
US9962361B2 (en) | 2011-01-03 | 2018-05-08 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactants, formulations incorporating the same, and associated methods of use |
US11407713B2 (en) | 2011-01-03 | 2022-08-09 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactants, formulations incorporating the same, and associated methods of use |
US10640464B2 (en) | 2011-01-03 | 2020-05-05 | The William M. Yarbrough Foundation | Use of isothiocyanate functional surfactants as Nrf2 inducers to treat epidermolysis bullosa simplex and related diseases |
US10273205B2 (en) | 2011-01-03 | 2019-04-30 | The William M. Yarbrough Foundation | Isothiocyanate functional surfactants, formulations incorporating isothiocyanate functional surfactants and associated methods for treating biofilms |
US8933119B2 (en) | 2011-01-03 | 2015-01-13 | The William M. Yarbrough Foundation | Method for treating phytophotodermatitis |
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EP2678029B1 (en) | 2011-02-22 | 2016-11-09 | Caudill Seed Company, Inc. | Spray dried myrosinase and use to produce isothiocyanates |
ES2425294B1 (es) * | 2012-03-09 | 2014-09-02 | Consejo Superior De Investigaciones Científicas (Csic) | Compuestos derivados de sulforafano, método de obtención y su uso médico, alimenticio y cosmético |
CN102697764A (zh) * | 2012-05-03 | 2012-10-03 | 苏州纳晶医药技术有限公司 | 一种含有异硫氰酸苯乙酯的肠溶固体制剂 |
JP2015519358A (ja) * | 2012-06-01 | 2015-07-09 | ファームアグラ・ラブズ,インコーポレイテッド | スルフォラファンの単離及び精製 |
PL2854861T3 (pl) | 2012-06-01 | 2018-02-28 | Pharmagra Labs Inc | Sposób syntetyzowania sulforafanu |
US10441561B2 (en) | 2012-07-26 | 2019-10-15 | The William M. Yanbrough Foundation | Method for treating benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer |
US10434081B2 (en) | 2012-07-26 | 2019-10-08 | The William M. Yarbrough Foundation | Inhibitors of macrophage migration inhibitory factor |
US9839621B2 (en) | 2012-07-26 | 2017-12-12 | The William M. Yarbrough Foundation | Method for treating bladder cancer |
US10434082B2 (en) | 2012-07-26 | 2019-10-08 | The William M. Yarbrough Foundation | Isothiocyanate functional compounds augmented with secondary antineoplastic medicaments and associated methods for treating neoplasms |
WO2014018874A1 (en) | 2012-07-26 | 2014-01-30 | The William M. Yarbrough Foundation | Method for treating skin cancer |
US10080734B2 (en) | 2012-07-26 | 2018-09-25 | The William M. Yarbrough Foundation | Method for treating autism and other neurodevelopmental disorders |
US10335387B2 (en) | 2012-07-26 | 2019-07-02 | The William M. Yarbrough Foundation | Method for treating infectious diseases with isothiocyanate functional compounds |
US9949943B2 (en) | 2012-07-26 | 2018-04-24 | The William M. Yarbrough Foundation | Method for treating neurodegenerative diseases |
DE102014012367B3 (de) * | 2014-08-25 | 2015-08-27 | De Smaakmaker Holding B. V. | Verfahren zum Bestimmen der Konzentration von Glucoraphanin und/oder von Sulforaphan in einer Pflanze |
CN107468666B (zh) * | 2017-08-18 | 2021-01-01 | 赣州华汉生物科技有限公司 | 一种可稳定保存的萝卜硫素胶囊及其制备方法 |
CN111902046A (zh) * | 2018-02-02 | 2020-11-06 | 联邦科学技术研究组织 | 保护生物活性物和/或其前体 |
GB2574248B (en) * | 2018-05-31 | 2021-03-03 | Edwards Ltd | Foreline for a vacuum pump |
KR102457241B1 (ko) * | 2020-02-26 | 2022-10-21 | 경일대학교산학협력단 | 페닐이소티오시아네이트를 처리하여 십자화과 식물로부터 설포라판을 생산하는 방법 및 보존하는 방법 |
GB202005238D0 (en) | 2020-04-08 | 2020-05-20 | Evgen Pharma Plc | Crystalline complexes |
US20230150932A1 (en) * | 2020-04-23 | 2023-05-18 | Vio Chemicals Ag | Compositions for stabilizing an isothiocyanate |
CN117881648A (zh) * | 2021-09-13 | 2024-04-12 | 富士胶片株式会社 | 双环烷烃化合物的包合物的制造方法 |
CN113908294B (zh) * | 2021-11-02 | 2023-09-12 | 成都格纯生物医药有限公司 | 一种含花椰菜精制提取物的双包合物的制备方法和应用 |
WO2023133494A2 (en) * | 2022-01-06 | 2023-07-13 | Brassica Protection Products Llc | Oil-based isothiocyanate products and processes for preparing oil-based isothiocyanate products |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2888235A1 (fr) * | 2005-07-07 | 2007-01-12 | Nutrinov Sa | Procede d'extraction de sulforaphane a partir de broyat de crucifere contenant de la glucoraphanine |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US669984A (en) * | 1900-02-06 | 1901-03-19 | Josef Federmann | Spittoon. |
US673744A (en) * | 1900-08-06 | 1901-05-07 | Pearl M Westerfield | Vending-box. |
US5458903A (en) * | 1993-01-19 | 1995-10-17 | The Pillsbury Company | High fat biscuit mix and products resulting therefrom |
US5411986A (en) * | 1993-03-12 | 1995-05-02 | The Johns Hopkins University | Chemoprotective isothiocyanates |
JP3604172B2 (ja) * | 1994-03-22 | 2004-12-22 | 株式会社白元 | 除菌組成物、及び除菌方法 |
US5589504A (en) * | 1994-07-26 | 1996-12-31 | Cornell Research Foundation, Inc. | Treatment of newborn jaundice |
US6117429A (en) * | 1997-08-11 | 2000-09-12 | Weider Nutrition International, Inc | Compositions and treatments for reducing potential unwanted side effects associated with long-term administration of androgenic testosterone precursors |
US6699849B1 (en) | 1998-02-23 | 2004-03-02 | Cyclops, Ehf. | Cyclodextrin complexes of benzodiazepines |
FR2776666B1 (fr) * | 1998-03-31 | 2002-09-06 | Commissariat Energie Atomique | Complexes d'inclusion dans des cyclodextrines d'isothiocyanates organiques, en particulier bacteriostatiques, bactericides et/ou fongicides ou de leurs precurseurs naturels, et leur preparation |
US6048736A (en) * | 1998-04-29 | 2000-04-11 | Kosak; Kenneth M. | Cyclodextrin polymers for carrying and releasing drugs |
PT1109806E (pt) * | 1999-07-01 | 2004-02-27 | Italfarmaco Spa | Complexos de paroxetina com ciclodextrinas ou derivados de ciclodextrinas |
US6361812B1 (en) * | 1999-11-18 | 2002-03-26 | The Procter & Gamble Co. | Products comprising an isothiocyanate preservative system and methods of their use |
AU5440901A (en) * | 1999-12-20 | 2001-07-03 | Cognis France, S.A. | Cosmetic and/or pharmaceutical preparations |
US6433011B1 (en) * | 2000-03-08 | 2002-08-13 | American Health Foundation | Method for inhibiting formation of aberrant crypt foci in the colon of a mammal |
US6511675B2 (en) * | 2000-06-12 | 2003-01-28 | Access Business Group International, Llc | Composition and method for correcting a dietary phytochemical deficiency |
US6812248B2 (en) * | 2000-07-05 | 2004-11-02 | John Hopkins University School Of Medicine | Prevention and treatment of degenerative diseases by glutathione and phase II detoxification enzymes |
KR100880498B1 (ko) * | 2000-08-21 | 2009-01-28 | 제드 더블유. 파헤이 | 이소티오시아네이트에 의한 헬리코박터의 처리 |
JP2002187842A (ja) * | 2000-12-19 | 2002-07-05 | Toyo Shinyaku:Kk | ケール加工品およびその加工方法 |
JP2003146803A (ja) * | 2001-11-13 | 2003-05-21 | Carex Inc | 抗菌性粉末組成物およびその製造方法 |
CA2603235A1 (en) * | 2005-03-28 | 2006-10-05 | Bioresponse, Llc | Diindolylmethane-based compositions and methods of use thereof for promoting oral mucosal and bone health |
CN101120948A (zh) * | 2006-08-08 | 2008-02-13 | 普文英 | 一种具有化学保护、癌症预防和治疗用途的化合物组合物 |
CA2672971C (en) * | 2007-01-23 | 2014-03-11 | Pharmagra Labs, Inc. | Stabilized sulforaphane |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2888235A1 (fr) * | 2005-07-07 | 2007-01-12 | Nutrinov Sa | Procede d'extraction de sulforaphane a partir de broyat de crucifere contenant de la glucoraphanine |
Non-Patent Citations (3)
Title |
---|
OHTA Y ET AL.: "Kinetic and Thermodynamic Analyses of the Cyclodextrin-Allyl Isothiocyanate Inclusion Complex in an", BIOSCI.BIOTECHNOL.BIOCHEM., vol. 63(7), JPN6013016323, 1994, pages 190 - 193 * |
OHTA Y ET AL.: "Retarding Effect of Cyclodextrins on the Decomposition of Organic Isothiocyanates in an Aqueous Solu", BIOSCI.BIOTECHNOL.BIOCHEM, vol. 68(3), JPN6013016324, 2004, pages 671 - 675 * |
服部憲治郎 監修,寺尾啓二 著: "第1節 6.ワサビ香気成分(アリルイソチオシアネート、AITC)の安定化", 食品開発者のためのシクロデキストリン入門, JPN6013016320, September 2004 (2004-09-01), pages 118 - 119 * |
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