TWI410258B - 維生素及礦物質補充劑中穩定性之改良 - Google Patents
維生素及礦物質補充劑中穩定性之改良 Download PDFInfo
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- TWI410258B TWI410258B TW097105459A TW97105459A TWI410258B TW I410258 B TWI410258 B TW I410258B TW 097105459 A TW097105459 A TW 097105459A TW 97105459 A TW97105459 A TW 97105459A TW I410258 B TWI410258 B TW I410258B
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- Prior art keywords
- vitamin
- composition
- multivitamin
- mineral
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Description
本發明係關於營養補充劑組合物。更特定言之,本發明提供一種減少維生素及礦物質補充劑中與多組份營養補充劑錠劑隨時間產生之暗色化及/或起斑相關的降解之組合物及方法。
早已確認多種通常稱為維生素及礦物質之化合物對維持個體健康狀態及/或治療特定醫學病況(甚至在以相對較少之量提供時)提供重要價值。人體不能合成大多數維持人體健康所必需之維生素及礦物質。因此,維生素及礦物質必須自外部來源獲得。兩種最常見的外部來源為食物及營養補充劑。由於大多數人食用的食物不會始終提供必要每日需求量之維生素及礦物質,因此維生素及礦物質營養補充已成為一種公認的滿足醫學及健康接受標準之方法。
可投與維生素及礦物質製劑來治療特定醫學病況或作為一般營養補充劑。由於存在多種所需維生素及礦物質且每日所需量相對較小,因此便利地作為一般補充劑以錠劑或膠囊形式投與維生素與礦物質之混合物。市售多維生素及礦物質補充劑之典型每日劑量為每日一或兩顆錠劑或膠囊。該等組合物通常包括24種或24種以上之營養劑以及製造劑型所需要之賦形劑。
相應地,並不意外在此等複雜混合物中可能發生不當的化學相互作用。此等反應中最常見降解反應,其導致壓實
營養劑之效力降低且亦可導致組合物暗色化或顯現令人不悅之黑斑。氧化反應為例示性降解反應之常見形式。水之存在亦可直接或(例如)藉由促進諸如氧化反應之反應來促成降解。
例如,已發現水及脂溶性維生素組份(諸如抗壞血酸(維生素C)及α-生育酚乙酸酯(維生素E))對多組份補充劑組合物中濕氣誘導之化學降解敏感。抗壞血酸氧化作用受到飲食補充劑組合物中抗壞血酸與多價金屬離子之相互作用促進且在水存在下受到促進,其可導致錠劑暗色化及/或起斑及可能影響組份在體內利用之可用性的延長崩解時間。
傳統觀念認為促成降解之水為最接近組合物的環境中之水(例如環境水)及/或與組合物之表面或界面區域鬆散締合之水。舉例而言,市售營養補充產品One-A-DayActive包括一儲存說明,其標明"若過量濕氣進入瓶內,則鐵可能在錠劑上導致起斑"。
相應地,已使用乾燥劑來改良穩定性。然而,關於乾燥劑存在若干問題。首先,乾燥劑可能被消費者實際移出封裝而取消有益效應。其次,乾燥劑可能隨時間失效及/或具有移除結合水之能力侷限性。再次,乾燥劑增加最終產品之費用。
藉由使用錠劑塗層來限制錠劑內容物曝露於環境水亦已得到使用。儘管此方法可掩蓋消費者視覺方面的問題,但目前所用之聚合膜塗層不能明顯地減少起斑及/或暗色化問題。老化的經塗覆錠劑之檢查通常會發現塗層下方起斑
或核心暗色化。
Shah等人在"A Study of the Chemical and Physical Stability of Ascorbic Acid, Folic Acid, and Thiamine Hydrochloride Tablets Formulated With Emcompress Standard"中報導Emcompress Standard(直接壓縮性磷酸二鈣二水合物造粒)誘導抗壞血酸及硫胺鹽酸鹽錠劑中之抗壞血酸化學降解及物理降解(關於崩解時間)(Shah, D.H.& Aramblo,A.,1975,Drug Devel.&Ind.Pharm.
,1,459-505)。該參考文獻將此等不穩定性歸結於與環境中之水或與組合物表面或界面區域鬆散締合之水相關的濕氣。
因此,由於受濕氣促進之降解反應導致含有礦物質離子及可氧化維生素之多組份營養補充劑失去功效及/或不悅目之變色,故需要減少多組份營養補充劑中受濕氣促進之降解的組合物及/或方法。
本發明提供一種包含多維生素及礦物質組合物之醫藥組合物,該多維生素及礦物質組合物包含至少一種多價金屬及至少一種可氧化維生素,其中該組合物實質上不含可動結合水。在一例示性實施例中,該至少一種多價金屬係選自由以下各物組成之群:鐵、鎂、鋅、硒、銅、鈷、錳、鉬、釩、鎳、錫及鉻及其組合。在一例示性實施例中,該可氧化維生素係選自由以下各物組成之群:維生素C、維生素E、維生素A、維生素A前驅體、維生素B6
、維生素D3
、維生素K、葉酸及其組合。
在一較佳實施例中,該組合物進一步包含無水磷酸二鈣。在另一較佳實施例中,該組合物為錠劑劑型。
提供一種用於製備本發明之多維生素及礦物質組合物之方法。該方法包含提供至少一種可氧化維生素、至少一種多價金屬離子及無水磷酸二鈣,及將至少一種多價金屬離子、至少一種可氧化維生素及無水磷酸二鈣組合以形成組合物,其中該組合物實質上不含可動結合水。
提供一種用於減少多維生素及礦物質組合物補充劑錠劑中氧化作用誘導之起斑之方法。該方法包含將至少一種選自由鐵、鎂、鋅、硒、銅、鈷、錳、鉬、釩、鎳、錫及鉻及其組合組成之群之多價金屬與至少一種選自由維生素C、維生素E、維生素A、維生素A前驅體、維生素B6
、維生素D3
、維生素K、葉酸及其組合組成之群之可氧化維生素組合以形成組合物,其中該組合物實質上不含可動結合水。
本發明提供一種營養補充劑組合物,其包含至少一種多價金屬及至少一種可氧化維生素,具有實質上改良之對導致暗色化及/或起斑之反應及可降低可氧化維生素效力之反應的抗性。本發明亦包括用於製造該組合物之方法及用於防止或減少氧化、改良可氧化維生素之穩定性及穩定多維生素及礦物質營養補充劑組合物之崩解時間的方法。
不希望受限於理論,本發明者認為將結合水(傳統上認為在周圍條件或接近周圍條件下不能參與化學反應)減少
至最低限度對於將包含多價金屬離子及可氧化維生素之多維生素及礦物質組合物之起斑及/或暗色化減少至最低限度具有重要意義。
在一較佳實施例中,該組合物包含維生素C及多價金屬離子及無水磷酸二鈣,其中該組合物實質上不含可動結合水。本發明係關於解決對於觀察者而言顯現乾燥狀態且由經充分表徵之維生素、礦物質及相關物質製備之習知商業多維生素及礦物質錠劑中的問題。
除改良之化學穩定性以外,本發明之組合物通常亦具有改良之隨時間保持的錠劑崩解時間一致性,且對於與商品存放期相一致的錠劑隨時段產生之暗色化及/或起斑具有抗性。
咸信多價金屬陽離子充當維生素氧化之催化劑且該過程顯現為受到水之存在所促進。傳統上認為環境水或鬆散締合之表面或間隙水為在多價金屬離子存在下促進維生素氧化之水的來源。觀察結果由以下事實支持,即維生素氧化作為因濕度增加且在較低程度上因溫度增加而加速。然而,儘管此水來源可為一種因素,但在此等來源提供可忽略之量的水時起斑仍可發生。
無疑,防止含有複數種維生素及礦物質之多維生素及礦物質補充劑錠劑曝露於濕氣將有助於維持化學及物理穩定性,但通常不能充分地防止多維生素及礦物質補充劑在商業存放期內起斑及/或對一段時間後崩解時間之延長產生顯著影響。本發明者已發現,傳統上認為在周圍條件或接
近周圍條件下不能用於反應之結晶結構之水合水可能在導致多維生素及礦物質補充劑錠劑起斑之多價金屬陽離子存在下在維生素氧化反應中發揮一定作用。本發明提供將固體劑型中可用於反應之內部結合水(例如可動結合水)減少至最低程度。在一例示性實施例中,藉由使用無水磷酸二鈣作為礦物質/賦形劑(例如,作為鈣及磷之來源及作為稀釋劑及/或黏結劑)及避免使用具有水合水之鈣鹽而將抗壞血酸(例如維生素C)與多價金屬陽離子相互作用之傾向降至最低。
如本文中所用,術語"降解"意謂既定化學物質改變為不同的化學物質(例如化學改變)。本發明尤其關注產生起斑及/或降低組份或化合物之效力或兩者均存在之化學改變。
如本文中所用,"崩解時間"乙詞意謂營養補充劑之錠劑劑量單元在受控實驗室條件下崩解所用之時間量。一般技術者熟習測定崩解時間之方法及程序。
如本文中所用,術語"穩定性"可指化學穩定性及/或物理穩定性。如本文中所用,"化學穩定性"乙詞意謂化合物隨時間維持其化學特性之能力。相應地,穩定性意指化學物質(例如)耐氧化或其他降解之能力。如本文中所用,短語"物理穩定性"意謂組合物隨時間維持一致物理性質之能力。組合物隨時間維持一致崩解時間之能力為例示性物理穩定性。
如本文中所用,"可動結合水"乙詞意謂經由某種鍵結形
式連接至化學實體且在周圍條件或接近周圍條件下可變成用以促進化學反應之結合水。水合水,尤其是磷酸二鈣二水合物結晶結構中之水合水,為例示性的可動結合水。儘管一般被認為在周圍條件或接近周圍條件下(例如,典型運輸、儲存及使用條件下)是結合且穩定的,但是,在可氧化維生素及多價金屬離子存在下,水合水形式之結合水可促進氧化反應。如本文中所用,術語"實質上不含可動結合水"意謂在周圍條件或接近周圍條件下可用於反應之水合水或其他形式之結合水佔組合物之少於0.3重量%。(該0.3%或更少之量包括(例如)少於0.25%,或少於0.2%,或少於0.15%,或少於0.1%,或少於0.5%)。因此,較佳係避免使用含有可動結合水之組份,但實質上不含可動結合水乃確認與營養劑締合之極少量水合水可以使用及/或指定為無水之組合物中可存在微量水合形式之水。可動結合水之最大值可藉由對含有水合水之各組份的水合水質量求總和且將其與組合物之總質量作比較以求出百分比來進行計算。
術語"多維生素及礦物質"或"多維生素及多礦物質"補充劑應解釋為意謂由特定維生素及礦物質材料製備之習知商業類型維生素及礦物質補充劑。多維生素及礦物質補充劑包括包含至少一種維生素及至少一種礦物質且視情況包含相關營養劑(諸如類胡蘿蔔素)之組合物。然而,如本文中所用,術語"多維生素及礦物質補充劑"不包括含有複雜植物提取物(諸如複雜多組份草本提取物)之補充劑及/或含有
大量額外增加補充劑組合物之複雜性的疏水性材料(例如多於30%之高度疏水性材料,諸如植物甾醇)之組合物。換言之,本發明係關於解決與含有複數種維生素及複數種礦物質之通常稱為多維生素及礦物質補充劑之習知大規模產生的營養補充劑相關之問題。當術語"多維生素及礦物質"或"多維生素及多礦物質"置於術語"營養補充劑"、"錠劑"或"組合物"之前時,在本文中其應以同等方式解釋。
術語"效力"與有效組份之量有關。通常,如本文中所用,其係指既定組份在既定時間與同一組份在第二時間之有效量相比較的有效量。通常,效力係以百分比表示。舉例而言,3個月後組份A之效力降低20%意謂3個月時期後所存在之組份A的有效量為組份A的原始有效量之80%。
如本文中所用,術語"多價金屬"意謂具有2價或2價以上之金屬離子。
如本文中所用,術語"可氧化維生素"可適用於可經歷氧化降解且氧化作用可受到水及多價金屬之存在促進之脂溶性或水溶性維生素。可氧化維生素包括(但不限於)維生素C、維生素E、維生素A、維生素A前驅體、維生素B6
、維生素D3
、維生素K及葉酸。
如上文所討論,本發明解決可氧化維生素與多價金屬離子在可動結合水存在下之不當相互作用問題。因此,本發明適用於含有一種可氧化維生素及一種多價金屬離子之固體形式組合物,而無論該可氧化維生素及該多價金屬離子為唯一活性劑或維生素與礦物質之混合物之一部分。如上
所述,本發明尤其係關於商業多維生素及礦物質補充劑中可見之類型的維生素與礦物質之複雜混合物。可包括於營養補充劑中之維生素及礦物質以及相關藥劑與劑量之清單陳述於確認的參考指南中,諸如美國藥典國家處方集官方標準綱要(United States Pharmacopeia National Formulary Official Compendium of Standards)(亦即U.S.P.-N.F.官方標準綱要)或歐洲指令(European Directive)90/496/EC(包括修正案),其均以引用的方式併入本文中。在特定實施例中維生素及礦物質之量可不同,但其通常應在U.S.P.-N.F.官方標準綱要或歐洲聯合指令所陳述之劑量範圍內。
可包括於多維生素及礦物質製劑中之維生素及相關實體包括(但不限於)維生素C、維生素E、硫胺(維生素B1
)、核黃素(維生素B2
)、菸鹼(維生素B3
)、吡哆醇(維生素B6
)、葉酸、鈷胺素(維生素B12
)、泛酸(維生素B5
)、生物素、維生素A(及維生素A前驅體)、維生素D、維生素K、其他B族複合維生素、B族複合相關化合物(諸如膽鹼及肌醇)及類胡蘿蔔素(諸如葉黃素、番茄紅素、玉米黃素及葉黃素色素)。在此等維生素中,已知維生素C、維生素E、維生素A、維生素B6
、維生素D3
、維生素K及葉酸對多維生素及礦物質製劑中之氧化作用敏感。在上文所列之維生素中,維生素C及維生素E尤其對多價金屬離子存在下之氧化作用敏感。
維生素C通常係以抗壞血酸形式提供於多維生素-多礦物質錠劑中。由於抗壞血酸尤其對於氧化作用敏感,因此其
通常係起斑及暗色化之重要促成因子。或者,可使用具有降低之水親和力之抗壞血基棕櫚酸酯(一種維生素C之疏水性酯)。使用抗壞血基棕櫚酸酯可觀察到起斑減少,但使用抗壞血基棕櫚酸酯具有需要謹慎考慮之缺點。抗壞血基棕櫚酸酯與抗壞血酸相比相對較貴且效力低於抗壞血酸(42.5%維生素C效力),從而需要較高使用含量且消費者需吞服較大錠劑。抗壞血基棕櫚酸酯亦具有較差粉末流動性質,此等性質尤其會在壓縮期間導致處理問題且通常產生在產品存放期時段內經歷崩解時間實質性增加之錠劑。
用各種障壁塗層塗佈或囊封抗壞血酸為防止或減緩氧化之可能性替代方法。本發明者探查了此策略,但所進行之實驗發現聚合膜塗層對錠劑崩解具有不當的負面影響。因此,本發明者發現水合水可促進維生素C氧化且在包含維生素C之組合物中避免包括具有可動結合水之組份,其可提供用於減少導致暗色化或起斑之降解反應的實用、低成本方法。
維生素E通常係以D1-α生育酚乙酸酯之形式提供於多維生素及礦物質錠劑中。如同維生素C,已發現維生素E對於多價金屬離子存在下濕氣誘導之化學降解尤其敏感。通常,維生素E氧化作用不會顯著促成起斑,但維生素E之氧化作用會導致其效力隨時間明顯降低。因此,維生素E之氧化作用可影響營養補充劑隨時間之品質。同樣,在包含維生素E之組合物中避免包括具有可動結合水之組份會減少維生素E之氧化。
可包括於多維生素及礦物質補充劑中之礦物質包括(但不限於)鐵、碘、鎂、鋅、硒、銅、鈣、錳、矽、鉬、釩、硼、鎳、錫、磷、鉻、鈷、氯化物及鉀。多維生素-多礦物質錠劑之礦物質組份通常係以鹽形式提供。所用之鹽形式應為醫藥學上可接受之鹽形式。
在一些情況下,該等鹽可為具有結晶結合水之水合形式。對於一些水合鹽(例如磷酸二鈣二水合物)而言,結晶結合水為在周圍條件或接近周圍條件下可用於促進氧化反應之可動結合水。因此,避免使用含有可動結合水之鹽形式會移除水之重要來源且降低受濕氣促進之氧化反應發生的傾向。使用無水磷酸二鈣作為鈣來源/賦形劑來替代常用的磷酸二鈣二水合物為例示性的。通常可避免具有水合水之鹽,或由於傳統上認為結晶結構中之水合水在周圍條件下不可用,可進行測試來判定水合鹽是否可促成氧化過程。該測試可以若干種方式中之任一方式來完成。舉例而言,可製備包含水合鹽、可氧化維生素及多價金屬離子之測試組合物且使其經歷穩定性測試。
多種礦物質鹽包含多價金屬離子。舉例而言,鐵、鎂、鋅、硒、銅、鈷、錳、鉬、釩、鎳、錫及鉻通常係以鹽形式提供,其中該金屬為多價狀態。任何多價金屬離子均可催化氧化反應;然而,已知鐵及銅離子尤其會在多維生素及礦物質組合物中引起問題。
儘管與多維生素及礦物質組合物中所用之任何鹽締合之水合水均可為潛在的可動結合水來源,但本發明者已鑑別
常用之水合鈣鹽尤其會引起問題。磷酸二鈣二水合物常用於商業多維生素及礦物質製劑中,因為其為提供若干效益之低成本成份。除提供鈣及磷營養劑外,其亦為適用於製備錠劑之賦形劑,充當黏結劑及/或稀釋劑。由於磷酸二鈣具有賦形劑/營養劑作用,商業多維生素及礦物質錠劑常包含顯著量之磷酸二鈣。
因此,至少由於使用量之原因,排除使用常見水合形式之磷酸二鈣可減少顯著量的可用於促進不當氧化反應之可動結合水。在一實施例中,排除與磷酸二鈣締合之可動結合水係藉由使用無水磷酸二鈣而達成。無水磷酸二鈣提供鈣及磷營養劑效益及賦形劑效益,而無任何促成不當氧化反應之可動結合水。儘管使用無水磷酸二鈣一般係有益的,但在包含大量鈣之組合物(例如,每個錠劑包含150 mg以上元素鈣之組合物)中係尤其有益的。此外,無水磷酸二鈣可用作多維生素及礦物質組合物中之唯一元素鈣來源,或者與其他鈣來源(諸如碳酸鈣)組合使用。
本發明之多維生素及礦物質營養組合物意欲以固體形式口服投與。因此,為形成固體劑型,該組合物除包含維生素及礦物質以外可進一步包含賦形劑及/或處理助劑。例示性賦形劑及處理助劑包括(但不限於)吸收劑、稀釋劑、調味劑、著色劑、穩定劑、填充劑、黏結劑、崩解劑、潤滑劑、濕潤劑、助流劑、防黏劑、糖或塗膜劑、防腐劑、緩衝劑、人工甜味劑、天然甜味劑、分散劑、增稠劑、增溶劑及其類似物或其某一組合。
通常,熟習此項技術者已知之賦形劑及處理助劑均適用於本發明之多維生素及礦物質組合物,只要其不包括可促進氧化反應之水。舉例而言,在一些含有抗壞血酸之實施例中,可需要避免使用澱粉作為賦形劑來使抗壞血酸成粒,因為澱粉係吸濕的。適用於抗壞血酸之例示性造粒劑為HPMC(羥基丙基甲基纖維素)。
本發明組合物之劑型為固體。然而,固體劑型可含有非水性液體或半固體組份。例示性固體劑型包括(但不限於)錠劑、囊片(caplets)、膠囊、可咀嚼劑型、粉末、藥囊及其類似物。每日劑量可包括於單一傳遞單元中或可包含多個傳遞單元。若使用錠劑,則可需要將每日劑量分為多個傳遞單元,例如用以提供便於吞服之錠劑尺寸。若使用多個傳遞單元,則其必要時可一次性投與或在劑量週期(例如,通常為1天)內間隔投與。因此,應瞭解本文所揭示之維生素、礦物質或其他相關營養劑之任何量均係關於每日劑量而言且劑量可以單一傳遞單元或多個傳遞單元傳遞。此外,劑量係關於指定營養劑物質之量而言,且任何與指定物質締合之相對離子及/或配位體之質量均不包括在指定量中。
在一較佳實施例中,多維生素及礦物質補充劑為藉由直接壓縮方法製備之錠劑,在製造過程中避免使組合物曝露於液體水。可將組合物之成份預摻合,隨後組合,或經由其他乾式造粒方法組合。或者,可使用濕式造粒。然而,若使用濕式造粒及/或水基塗層,則應設計處理步驟以限
制在處理中曝露於水且在完成造粒及/或塗佈之後提供有效的乾燥。
本發明之例示性實施例之組合物之三個實例提供於表1、2及3中。此等組合物為本發明範疇內之多種組合物之代表及實例且係出於說明性目的而提供。表1-3中例示之多維生素及礦物質營養補充劑意欲為每日劑量,且通常將以一或多個劑量單元(例如,一或多個錠劑)投與。若使用多個劑量單元,則其可一次性或在一天內間隔分開服用。所指示之量屬於指定營養組份且不包括任何相對離子之質量。因此,指定組份可衍生自任何醫藥學上可接受之化合物或鹽。此外,實例給出營養劑(例如,維生素或礦物質)之量,且應瞭解指定營養劑可與一或多種賦形劑組合以製備最終劑型。
表4顯示用無水磷酸二鈣製備之本發明例示性實施例之錠劑與除使用磷酸二鈣二水合物替代無水磷酸二鈣以外以
相同方式製備之相同成份組合相比較的穩定性數據。兩組錠劑均包含60 mg抗壞血酸(維生素C)/錠劑及30 IU維生素E/錠劑以及18 mg鐵(反丁烯二亞鐵形式)/錠劑、100 mg鎂(氧化鎂形式)/錠劑、2 mg銅(氧化銅形式)/錠劑、15 mg鋅(氧化鋅形式)/錠劑、2.5 mg錳(硫酸錳形式)/錠劑、5 mcg鎳(硫酸鎳形式)/錠劑及25 mcg鉻(氯化鉻形式)/錠劑之多價金屬陽離子。如上所示,兩組錠劑之間的區別僅在於一批係使用磷酸二鈣二水合物製備,而另一批係使用無水磷酸二鈣製備。在兩批中,每個錠劑之鈣量均為162 mg且每個錠劑之磷量均為125 mg。將錠劑儲存於受力條件下,在55℃/95%相對濕度("RH")下1週加上在40℃/75%RH下3個月。在測試週期之初及測試週期結束時檢查及測試錠劑。
如表4所示,在指定應力條件下,用無水磷酸二鈣製備之錠劑在測試週期結束時顯示出實質上高於用磷酸二鈣二水合物製備之錠劑的維生素C及E效力(例如,維生素C為90.8%對比於57.4%且維生素E為94.2%對比於62.5%)。用無水磷酸二鈣製備之錠劑的崩解時間亦顯示出實質上低於使用磷酸二鈣二水合物製備之錠劑之崩解時間的隨時間改變。
在3個月週期結束時目視檢查,用無水磷酸二鈣製備之錠劑未顯現起斑,而用磷酸二鈣二水合物製備之錠劑具有實質性內部及外部起斑。
儘管上文已出於清晰理解之目的而以說明及舉例方式在一定程度上詳細地描述本發明,但顯而易見在所附申請專利範圍之範疇內可實施某些改變及修改。熟習此項技術者顯而易見之上述本發明實施方式之修改意欲包括於以下申請專利範圍之範疇內。
Claims (33)
- 一種多維生素及礦物質組合物,其包含至少一種多價金屬及至少一種可氧化維生素,其中該組合物實質上不含可動結合水。
- 如請求項1之多維生素及礦物質組合物,其中該多價金屬係選自由鐵、鎂、鋅、硒、銅、鈷、錳、鉬、釩、鎳、錫、鉻及其組合組成之群。
- 如請求項1或2之多維生素及礦物質組合物,其中該可氧化維生素係選自由維生素C、維生素E、維生素A、維生素A前驅體、維生素B6 、維生素D3 、維生素K、葉酸及其組合組成之群。
- 如請求項1或2之多維生素及礦物質組合物,其進一步包含鈣鹽。
- 如請求項1或2之多維生素及礦物質組合物,其包含無水磷酸二鈣。
- 如請求項1或2之多維生素及礦物質組合物,其進一步包含類胡蘿蔔素。
- 如請求項1或2之多維生素及礦物質組合物,其包含維生素C及維生素E中之至少一者。
- 如請求項7之多維生素及礦物質組合物,其包含維生素C。
- 如請求項1或2之多維生素及礦物質組合物,其包含選自鐵及銅之多價金屬。
- 如請求項1或2之多維生素及礦物質組合物,其中該組合 物係呈固體劑型。
- 如請求項10之多維生素及礦物質組合物,其中該固體劑型係選自由錠劑、囊片(caplets)、膠囊、可咀嚼劑型、粉末、藥囊及其組合組成之群。
- 如請求項11之多維生素及礦物質組合物,其中該固體劑型為錠劑。
- 一種用於製備多維生素及礦物質組合物之方法,其包含:提供至少一種可氧化維生素、至少一種多價金屬離子及無水磷酸二鈣;及將該至少一種多價金屬離子、該至少一種可氧化維生素及無水磷酸二鈣組合以形成組合物,其中該組合物實質上不含可動結合水。
- 如請求項13之方法,其中該多價金屬係選自由鐵、鎂、鋅、硒、銅、鈷、錳、鉬、釩、鎳、錫、鉻及其組合組成之群。
- 如請求項13或14之方法,其中該可氧化維生素係選自由維生素C、維生素E、維生素A、維生素A前驅體、維生素B6 、維生素D3 、維生素K、葉酸及其組合組成之群。
- 如請求項13或14之方法,其進一步包含使該多維生素及礦物質組合物形成錠劑。
- 如請求項16之方法,其中該錠劑係藉由直接壓縮方法形成。
- 一種用於減少多維生素及礦物質錠劑中因氧化作用誘導之起斑之方法,其包含:將至少一種選自由鐵、鎂、鋅、硒、銅、鈷、錳、鉬、釩、鎳、錫、鉻及其組合組 成之群之多價金屬與至少一種選自由維生素C、維生素E、維生素A、維生素A前驅體、維生素B6 、維生素D3 、葉酸及其組合組成之群之可氧化維生素組合以形成組合物,其中該組合物實質上不含可動結合水;及使該組合物形成錠劑。
- 如請求項18之方法,其進一步包含將無水磷酸二鈣與該至少一種多價金屬及該至少一種可氧化維生素組合。
- 一種供人類補充營養之方法,其包含對人類提供有效量之多維生素及礦物質組合物,該組合物包含至少一種多價金屬及至少一種可氧化維生素,其中該至少一種多價金屬與該至少一種可氧化維生素係經組合以形成組合物,且其中該組合物實質上不含可動結合水。
- 一種多維生素及礦物質補充劑,其每日劑量包含至少一種選自由約15至約600 mg之維生素C及至少一種約20 IU至約200 IU之維生素E組成之群的維生素;至少一種選自由約0至約400 mg之鎂、約0至約50 mg之鋅、約0至約12 mg之錳、約0至約4 mg之銅、約0至約300 mcg之鉻及約0至約18 mg之鐵之多價金屬離子;及約100至約1500 mg之鈣,其中至少一部分鈣係以無水磷酸二鈣之形式提供,且其中該補充劑實質上不含可動結合水。
- 如請求項21之多維生素及礦物質補充劑,其係呈錠劑型式。
- 如請求項22之多維生素及礦物質補充劑,其中該錠劑係藉由直接壓縮而形成。
- 一種多維生素及礦物質組合物,其包含每個劑量單元至少150 mg之元素鈣、至少一種多價金屬及至少一種可氧化維生素,其中該組合物實質上不含可動結合水。
- 如請求項24之多維生素及礦物質組合物,其中該多價金屬係選自由鐵、鎂、鋅、硒、銅、鈷、錳、鉬、釩、鎳、錫、鉻及其組合組成之群。
- 如請求項24或25之多維生素及礦物質組合物,其中該可氧化維生素係選自由維生素C、維生素E、維生素A、維生素A前驅體、維生素B6 、維生素D3 、維生素K、葉酸及其組合組成之群。
- 如請求項24或25之多維生素及礦物質組合物,其中該可氧化維生素為維生素C。
- 如請求項24或25之多維生素及礦物質組合物,其中該組合物係呈固體劑型。
- 如請求項28之多維生素及礦物質組合物,其中該固體劑型係選自由錠劑、囊片、膠囊、可咀嚼劑型、粉末、藥囊及其組合組成之群。
- 如請求項29之多維生素及礦物質組合物,其中該固體劑型為錠劑。
- 如請求項24或25之多維生素及礦物質組合物,其中該元素鈣係以無水磷酸二鈣之形式提供。
- 如請求項24或25之多維生素及礦物質組合物,其中該元素鈣之第一部分係以無水磷酸二鈣之形式提供。
- 一種用於穩定多維生素及礦物質錠劑隨時間之崩解行為 之方法,其包含:將至少一種選自由鐵、鎂、鋅、硒、銅、鈷、錳、鉬、釩、鎳、錫、鉻及其組合組成之群的多價金屬與至少一種選自由維生素C、維生素E、維生素A、維生素A前驅體、維生素B6 、維生素D3 、葉酸及其組合組成之群的可氧化維生素組合以形成組合物,其中該組合物實質上不含可動結合水;及使該組合物形成錠劑。
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