JP2017519046A - 甘味受容体アンタゴニスト組成物 - Google Patents
甘味受容体アンタゴニスト組成物 Download PDFInfo
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- JP2017519046A JP2017519046A JP2017517220A JP2017517220A JP2017519046A JP 2017519046 A JP2017519046 A JP 2017519046A JP 2017517220 A JP2017517220 A JP 2017517220A JP 2017517220 A JP2017517220 A JP 2017517220A JP 2017519046 A JP2017519046 A JP 2017519046A
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- Prior art keywords
- zinc
- gymnemic acid
- composition
- acid
- sweetness
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000000203 mixture Substances 0.000 title claims abstract description 124
- 239000002464 receptor antagonist Substances 0.000 title 1
- 229940044551 receptor antagonist Drugs 0.000 title 1
- 229930183009 gymnemic acid Natural products 0.000 claims abstract description 177
- 235000019658 bitter taste Nutrition 0.000 claims abstract description 65
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 54
- 239000011701 zinc Substances 0.000 claims abstract description 47
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 32
- 235000009508 confectionery Nutrition 0.000 claims abstract description 20
- 235000019577 caloric intake Nutrition 0.000 claims abstract description 7
- 239000003112 inhibitor Substances 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 33
- 239000012453 solvate Substances 0.000 claims description 13
- -1 zinc halide Chemical class 0.000 claims description 12
- 101710084933 Miraculin Proteins 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 235000006679 Mentha X verticillata Nutrition 0.000 claims description 8
- 235000002899 Mentha suaveolens Nutrition 0.000 claims description 8
- 235000001636 Mentha x rotundifolia Nutrition 0.000 claims description 8
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 8
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 8
- 239000006191 orally-disintegrating tablet Substances 0.000 claims description 8
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 8
- 239000011670 zinc gluconate Substances 0.000 claims description 8
- 235000011478 zinc gluconate Nutrition 0.000 claims description 8
- 229960000306 zinc gluconate Drugs 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 239000007937 lozenge Substances 0.000 claims description 7
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 7
- 229960001763 zinc sulfate Drugs 0.000 claims description 7
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 7
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- 239000000843 powder Substances 0.000 claims description 5
- 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 description 5
- NLMDJJTUQPXZFG-UHFFFAOYSA-N 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane Chemical compound C1COCCOCCNCCOCCOCCN1 NLMDJJTUQPXZFG-UHFFFAOYSA-N 0.000 claims description 4
- FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 claims description 4
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 4
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- 235000015110 jellies Nutrition 0.000 claims description 4
- 239000008274 jelly Substances 0.000 claims description 4
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- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 claims description 4
- 239000004246 zinc acetate Substances 0.000 claims description 4
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- 239000011667 zinc carbonate Substances 0.000 claims description 4
- 235000004416 zinc carbonate Nutrition 0.000 claims description 4
- 229910000010 zinc carbonate Inorganic materials 0.000 claims description 4
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- 239000011746 zinc citrate Substances 0.000 claims description 4
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- PENRVBJTRIYHOA-UHFFFAOYSA-L zinc dithionite Chemical compound [Zn+2].[O-]S(=O)S([O-])=O PENRVBJTRIYHOA-UHFFFAOYSA-L 0.000 claims description 4
- 239000011787 zinc oxide Substances 0.000 claims description 4
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- 229960001939 zinc chloride Drugs 0.000 claims description 3
- ZULTYUIALNTCSA-UHFFFAOYSA-N zinc hydride Chemical compound [ZnH2] ZULTYUIALNTCSA-UHFFFAOYSA-N 0.000 claims description 3
- 229910000051 zinc hydride Inorganic materials 0.000 claims description 3
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- 210000000214 mouth Anatomy 0.000 abstract description 42
- 230000000903 blocking effect Effects 0.000 abstract description 9
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose 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)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 21
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Abstract
Description
本出願は、米国特許法第119条(e)により、2014年6月12日に出願された米国特許仮出願第62/011,096号および2014年7月17日に出願された米国特許仮出願第62/025,725号の優先権を主張する。これらはともに、参照により本明細書に組み込まれる。
配合物FLLC−F27c 4mg(長期放出配合物)
活性剤と1グラムのエリトリトールおよびグルコン酸亜鉛を共ミリングし、均一な微粉末にする。 残りの賦形剤を30メッシュスクリーンに通して分級する。次いで、ステアリン酸マグネシウム以外のすべての賦形剤を合わせる。
ステアリン酸マグネシウムを添加する
1分間ブレンドする
配合物を錠剤に圧縮する
本発明のギムネマ酸組成物の甘味ブロックの持続時間を定量するための標準方法を開発した。以下の実施例で使用したギムネマ酸は、ホウライアオカズラ(Gymnema sylvestre)の葉の粗製エキスを部分精製したものであり、ギムネマ酸の混合物(81%純度)であると測定され、この混合物は主にGA1とGA2であり、これより少ない量のGA3とGA4を有し、また、GAの酢酸/安息香酸ジエステル(即ち、GA34−ギムネモシドC)も含むものであった。すべての場合で、ショ糖を甘味ブロックの定量における甘味物質として使用した。従って、10%、8%、6%、4%および2%(w/v)のショ糖の逆浸透(RO)精製水中の溶液を、各実験の開始毎に新たに調製し、各ショ糖溶液の15mLのサンプルを甘味度の官能試験パネリストの較正に使用した。官能試験パネリストは、味覚(gustatation)の分野の官能評価の訓練を受け、官能試験パネリストとして少なくとも1年間の経験を有する人、好ましくは記述的分析の訓練を受けている人と説明される。甘味度(SI)の定量には、以下の評価段階:
10%ショ糖=10、
8%ショ糖=8、
6%ショ糖=6、
4%ショ糖=4、
2%ショ糖=2および
0%ショ糖=0
に基づいた標準的な段階評価方法論を使用した。
以下の本発明の実施例との比較対象のベースライン値を調べるため、ギムネマ酸を、この甘味抑制の持続時間を定量するために評価した。得られた結果を表1にまとめる。
ギムネマ酸との併用での潜在価値を調べるため、ラクチゾールを、この甘味抑制の持続時間を定量するために評価した。ラクチゾールは甘さブロッカーとしてギムネマ酸とは異なり、例えば、ラクチゾールによってもたらされる甘さブロックは、舌に曝露された後は長く続かない。しかしながら、驚くべきことに、口腔がラクチゾールに曝露された後、ラクチゾールを吐き出した後、即座に10%ショ糖参照をテイスティングした場合であっても甘味抑制は観察されないことが観察された。
ギムネマ酸(15mg)とラクチゾール(3mg)のブレンドの甘さ抑制
ギムネマ酸/ラクチゾールブレンドを、この甘味抑制の持続時間を定量するために評価した。得られた結果を表3にまとめる。
ギムネマ酸との併用での潜在価値を調べるため、ZnSO4・7H2Oを、この甘味抑制の持続時間を定量するために評価した。驚くべきことに、ZnSO4・7H2Oは、ギムネマ酸と同様、長時間の甘味抑制を引き起こしたが、甘さの感度が100%に回復したのは60分後であったため、ギムネマ酸の場合に近いほどは長時間でないことが観察された。得られた結果を表4にまとめる。
ギムネマ酸(15mg)とZnSO4・7H2O(107mg)のブレンドの甘さ抑制
次いで、ギムネマ酸/ZnSO4・7H2Oのブレンドを、甘味ブロックの持続時間について評価した。結果を表5にまとめる。
ギムネマ酸との併用での潜在価値を調べるため、ミラクリンを、この甘味抑制の持続時間を定量するために評価した。ミラクリンでの口腔の前処理後、甘味抑制効果は観察されなかった。得られた結果を表6にまとめる。
ギムネマ酸(15mg)とミラクリン(80mg)のブレンドの甘さ抑制
甘味抑制効果は観察されないにもかかわらず、それでもなお、ミラクリンをギムネマ酸との併用において評価し、ギムネマ酸の甘味抑制の持続時間が引き延ばされることが観察され得るかどうかを調べた。ミラクリンは、ギムネマ酸の甘味ブロックの持続時間を引き延ばすことが観察された。このため、ギムネマ酸と併用したミラクリンでは、甘味に対する相乗的抑制効果がもたらされる。結果を表7にまとめる。
ギムネマ酸(15mg)、ラクチゾール(3mg)およびZnSO4・7H2O(107mg)のブレンドの甘さ抑制
上記で実証されたように、ラクチゾールおよびZnSO4・7H2Oを独立して、ギムネマ酸と併用して使用した場合、甘さ抑制において相乗作用を示す。ギムネマ酸と併用したこれらの甘味抑制剤の両方を含有する3成分ブレンド組成物を評価し、相乗作用の増大が存在し得るかどうかを調べた。結果を表8にまとめる。
15mgのギムネマ酸の15mLのRO水中の溶液を評価し、苦さの15段階評価段階で10の苦さスコアを有することがわかった。
ギムネマ酸(15mg)とZnSO4・7H2O(107mg)のブレンドの苦さ
15mgのギムネマ酸の10mLのRO水中の溶液を107mgのZnSO4・7H2Oの5mLのRO水中の溶液と合わせ、評価した。0の苦さスコアを有することがわかった。それぞれ60、34、19、10.7、6および3.4mgのZnSO4・7H2Oを5mLのRO水中に含む水溶液を15mgのギムネマ酸(10mLのRO水サンプル中)と合わせた。得られた混合物は、それぞれ0、0、0、1、4および7の苦さ強度を示した。従って、このようなギムネマ酸/ZnSO4・7H2O組成物は、ZnSO4・7H2O濃度がおよそ0.6mg/mL(2mM)以上である場合、苦さがなくなることを示している。
Claims (25)
- ギムネマ酸および少なくとも1種類の形態の亜鉛を含む組成物。
- 送達形態が、ロゼンジ剤、口腔内崩壊錠、口腔内分散錠、トローチ、ハードキャンディ、ソフトキャンディ、ゼリー、ガム、可食フィルム、口腔内溶解性フィルム剤、ウエハース、ドロップ、オーラルスプレー、液剤、粉剤およびこの組合せからなる群より選択される、請求項1に記載の組成物。
- 送達形態が、約30秒から約5分間の範囲の崩壊時間を有する口腔内崩壊錠である、請求項2に記載の組成物。
- 該亜鉛の形態が、酢酸亜鉛、炭酸亜鉛、塩化亜鉛、クエン酸亜鉛、グルコン酸亜鉛、硫酸亜鉛、亜ジチオン酸亜鉛、重亜硫酸亜鉛、酸化亜鉛、ハロゲン化亜鉛、水素化亜鉛、炭化亜鉛およびこの組合せからなる群より選択される、請求項1に記載の組成物。
- 該亜鉛の形態がグルコン酸亜鉛である、請求項1に記載の組成物。
- ギムネマ酸が、ギムネマ酸の無機塩、ギムネマ酸の有機塩、ギムネマ酸のシクロデキストリン錯体、ギムネマ酸のクリプタンド錯体、ギムネマ酸の水和物、ギムネマ酸の溶媒和物およびこの組合せからなる群より選択される、請求項1に記載の組成物。
- ギムネマ酸の溶媒和物が、ギムネマ酸のエタノール溶媒和物およびこの組合せからなる群より選択される、請求項5に記載の組成物。
- 送達形態が、さらにミントを含んでもよい、請求項1に記載の組成物。
- 送達形態が、さらに苦味抑制剤を含んでもよく、該苦味抑制剤が、ナトリウム塩、リポタンパク質およびこの組合せからなる群より選択される、請求項1に記載の組成物。
- さらに少なくとも1種類の酸味抑制剤を含む、請求項1に記載の組成物。
- 少なくとも1種類の酸味抑制剤がミラクリンである、請求項8に記載の組成物。
- 請求項1に記載の組成物を含む舌上送達形態。
- 送達形態が、ロゼンジ剤、口腔内崩壊錠、口腔内分散錠、トローチ、ハードキャンディ、ソフトキャンディ、ゼリー、ガム、可食フィルム、口腔内溶解性フィルム剤、ウエハース、ドロップ、オーラルスプレー、液剤、粉剤およびこの組合せからなる群より選択される、請求項12に記載の舌上送達形態。
- 送達形態が、約30秒から約5分間の範囲の崩壊時間を有する口腔内崩壊錠である、請求項13に記載の舌上送達形態。
- 該亜鉛の形態が、酢酸亜鉛、炭酸亜鉛、塩化亜鉛、クエン酸亜鉛、グルコン酸亜鉛、硫酸亜鉛、亜ジチオン酸亜鉛、重亜硫酸亜鉛、酸化亜鉛、ハロゲン化亜鉛、水素化亜鉛、炭化亜鉛およびこの組合せからなる群より選択される、請求項12に記載の舌上送達形態。
- 該亜鉛の形態がグルコン酸亜鉛である、請求項12に記載の組成物。
- ギムネマ酸が、ギムネマ酸の無機塩、ギムネマ酸の有機塩、ギムネマ酸のシクロデキストリン錯体、ギムネマ酸のクリプタンド錯体、ギムネマ酸の水和物、ギムネマ酸の溶媒和物およびこの組合せからなる群より選択される、請求項12に記載の組成物。
- ギムネマ酸の溶媒和物が、ギムネマ酸のエタノール溶媒和物およびこの組合せからなる群より選択される、請求項17に記載の組成物。
- 送達形態が、さらにミントを含んでもよい、請求項12に記載の組成物。
- 送達形態が、さらに苦味抑制剤を含んでもよく、該苦味抑制剤が、ナトリウム塩、リポタンパク質およびこの組合せからなる群より選択される、請求項12に記載の組成物。
- さらに少なくとも1種類の酸味抑制剤を含む、請求項12に記載の組成物。
- 少なくとも1種類の酸味抑制剤がミラクリンである、請求項21に記載の組成物。
- 請求項1に記載の組成物を被験体に投与することを含む、砂糖消費量の低減方法。
- 請求項1に記載の組成物を被験体に投与することを含む、カロリー摂取量の低減方法。
- 請求項1に記載の組成物を被験体に投与することを含む、虫歯の低減方法。
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PCT/US2015/035578 WO2015192015A2 (en) | 2014-06-12 | 2015-06-12 | Sweet taste receptor antagonist compositions |
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US11484542B2 (en) | 2018-05-30 | 2022-11-01 | Adam Slank | Specialized tongue spray containing gymnemic acid and exogenous ketones |
WO2020208630A1 (en) * | 2019-04-09 | 2020-10-15 | Gyni S.G Ltd | Sweetness blocker composition |
WO2023195718A1 (ko) * | 2022-04-04 | 2023-10-12 | 서울대학교산학협력단 | 감미 억제용 조성물 및 식품의 감미 억제 방법 |
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US20190070254A1 (en) | 2019-03-07 |
CN106659215A (zh) | 2017-05-10 |
AU2015274362A1 (en) | 2016-12-08 |
US9421217B2 (en) | 2016-08-23 |
WO2015192015A2 (en) | 2015-12-17 |
US20170143793A1 (en) | 2017-05-25 |
MA40227A (fr) | 2017-04-19 |
US20160303149A1 (en) | 2016-10-20 |
SG11201609600UA (en) | 2016-12-29 |
KR20170020859A (ko) | 2017-02-24 |
US20150359809A1 (en) | 2015-12-17 |
US20210030839A1 (en) | 2021-02-04 |
US9585905B2 (en) | 2017-03-07 |
CA2953243A1 (en) | 2015-12-17 |
EP3154518A2 (en) | 2017-04-19 |
IL249466A0 (en) | 2017-02-28 |
BR112016028973A2 (pt) | 2017-08-22 |
MX2016016214A (es) | 2017-08-02 |
WO2015192015A3 (en) | 2016-02-04 |
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