TW201808980A - 2-O-[alpha]-D-glycosyl-L-ascorbic acid metal salts, their uses as an antioxidant and a manufacturing method of the metal salts powder - Google Patents
2-O-[alpha]-D-glycosyl-L-ascorbic acid metal salts, their uses as an antioxidant and a manufacturing method of the metal salts powder Download PDFInfo
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Abstract
Description
本發明係關於安定性優異之2-O-α-D-糖基-L-抗壞血酸金屬鹽、其作為抗氧化劑之用途及該金屬鹽之非晶質之粉末狀固體之製造方法。 The present invention relates to a method for producing 2-O-α-D-glycosyl-L-ascorbic acid metal salt with excellent stability, its use as an antioxidant, and an amorphous powdery solid of the metal salt.
屬於典型的2-O-α-D-糖基-L-抗壞血酸之2-O-α-D-葡吡喃糖基-L-抗壞血酸係具有下述化學式(2)所示之化學結構,且藉由水解而生成L-抗壞血酸與D-葡萄糖:
已知與L-抗壞血酸相比,2-O-α-D-葡吡喃糖基-L-抗壞血酸不容易氧化且安定性優異,另一方面,在體內容易水解而具有與L-抗壞血酸同等程度之生理活性(專利文獻1及2),期待在化妝品、食品及醫藥品等廣泛的應用。又,已知結晶之2-O-α-D-葡吡喃糖基-L-抗壞血酸係安定性特別優異(專利文獻1)。然而,2-O-α-D-葡吡喃糖基-L-抗壞血酸之溶液中之安定性有問題,並且就作為化妝品等皮膚外用劑所要求之保濕性之點而言不充分。又,已知2-O-α-D-葡吡喃糖基-L-抗壞血酸之鋁鹽及鋅鹽(專利文獻3)、鈉及鉀等鹼金屬鹽(專利文獻4)。 Compared with L-ascorbic acid, it is known that 2-O-α-D-glucopyranosyl-L-ascorbic acid is not easily oxidized and has excellent stability. On the other hand, it is easily hydrolyzed in the body to have the same level as L-ascorbic acid The physiological activity (Patent Documents 1 and 2) is expected to be widely used in cosmetics, foods, and pharmaceuticals. In addition, it is known that 2-O-α-D-glucopyranosyl-L-ascorbic acid based on crystals is particularly excellent in stability (Patent Document 1). However, the stability in the solution of 2-O-α-D-glucopyranosyl-L-ascorbic acid is problematic, and it is insufficient in terms of the moisturizing property required for skin external preparations such as cosmetics. In addition, aluminum salts and zinc salts of 2-O-α-D-glucopyranosyl-L-ascorbic acid (Patent Document 3), and alkali metal salts such as sodium and potassium are known (Patent Document 4).
[專利文獻1]日本特開平03-135992號公報 [Patent Document 1] Japanese Patent Laid-Open No. 03-135992
[專利文獻2]日本特開平03-183492號公報 [Patent Document 2] Japanese Patent Laid-Open No. 03-183492
[專利文獻3]日本特開平06-220081號公報 [Patent Document 3] Japanese Unexamined Patent Publication No. 06-220081
[專利文獻4]日本特開2002-088095號公報 [Patent Document 4] Japanese Patent Laid-Open No. 2002-088095
課題係提供具有高安定性且保濕性優異之2-O-α-D-糖基-L-抗壞血酸金屬鹽及2-O-α-D-糖基-L-抗壞血酸金屬鹽之作為抗氧化劑之用途。 The subject is to provide 2-O-α-D-glycosyl-L-ascorbic acid metal salt and 2-O-α-D-glycosyl-L-ascorbic acid metal salt with high stability and excellent moisture retention as antioxidants. use.
本發明者等專心研究之結果,發現2-O-α-D-糖基-L-抗壞血酸之第二族元素之鹽、及第二族元素與其他金屬之組合之鹽尤其安定性及保濕性優異,以及2-O-α-D-糖基-L-抗壞血酸之金屬鹽有用作為抗氧化劑,從而完成本發明。 As a result of intensive research by the present inventors, they found that salts of Group 2 elements of 2-O-α-D-glycosyl-L-ascorbic acid and salts of a combination of Group 2 elements and other metals are particularly stable and moisturizing. Excellent, and the metal salt of 2-O-α-D-glycosyl-L-ascorbic acid is useful as an antioxidant, thereby completing the present invention.
本發明之實施形態係例示如下。 An embodiment of the present invention is exemplified as follows.
(1)一種2-O-α-D-糖基-L-抗壞血酸金屬鹽,其係下述通式(1)所示之2-O-α-D-糖基-L-抗壞血酸之金屬鹽:
(式中,n係表示1至8之整數) (Where n is an integer from 1 to 8)
並且,金屬離子至少含有1種第二族元素之金屬離子。 The metal ion contains at least one metal ion of a second group element.
(2)如(1)所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽,其係2-O-α-D-糖基-L-抗壞血酸金屬鹽,且金屬離子更含有第一族元素之金屬離子。 (2) The 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to (1), which is a 2-O-α-D-glycosyl-L-ascorbic acid metal salt, and the metal ion is more Contains metal ions of Group I elements.
(3)如(1)或(2)所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽,其中,第二族元素之金屬離子對2-O-α-D-糖基-L-抗壞血酸之莫耳比係0.01至0.50、0.05至0.30、0.10至0.20、或0.01至0.20之範圍。 (3) The 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to (1) or (2), wherein the metal ion of the second group element is a 2-O-α-D-sugar The molar ratio of the base-L-ascorbic acid ranges from 0.01 to 0.50, 0.05 to 0.30, 0.10 to 0.20, or 0.01 to 0.20.
(4)如(1)至(3)中任一項所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽,其中,第二族元素之金屬離子係鎂離子。 (4) The 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to any one of (1) to (3), wherein the metal ion of the second group element is a magnesium ion.
(5)如(1)至(4)中任一項所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽,其中,鎂離子對2-O-α-D-糖基-L-抗壞血酸之莫耳比係0.01至0.50、0.05至0.30、0.10至0.20、或0.01至0.20之範圍。 (5) The 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to any one of (1) to (4), wherein the magnesium ion pairs 2-O-α-D-glycosyl The molar ratio of -L-ascorbic acid is in the range of 0.01 to 0.50, 0.05 to 0.30, 0.10 to 0.20, or 0.01 to 0.20.
(6)如(1)至(5)中任一項所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽,其中,2-O-α-D-糖基-L-抗壞血酸含有2-O-α-D-葡吡喃糖基-L-抗壞血酸。 (6) The 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to any one of (1) to (5), wherein the 2-O-α-D-glycosyl-L- Ascorbic acid contains 2-O-α-D-glucopyranosyl-L-ascorbic acid.
(7)如(6)所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽,其中,2-O-α-D-糖基-L-抗壞血酸更含有選自由2-O-α-D-麥芽糖基-L-抗壞血酸、2-O-α-D-麥芽三糖基-L-抗壞血酸所構成之群組之一種或該等之混合物。 (7) The 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to (6), wherein the 2-O-α-D-glycosyl-L-ascorbic acid further contains a member selected from 2-O -α-D-maltosyl-L-ascorbic acid, 2-O-α-D-maltotriosyl-L-ascorbic acid, or a mixture thereof.
(8)一種(1)至(7)中任一項所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽之非晶質粉末。 (8) An amorphous powder of the 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to any one of (1) to (7).
(9)一種皮膚外用劑,其係含有(8)所述之非晶質粉末 而成者。 (9) A skin external preparation containing the amorphous powder according to (8) Become.
(10)一種2-O-α-D-糖基-L-抗壞血酸金屬鹽之非晶質粉末之製造方法,其係包括:製作在水及/或醇之溶劑中溶解有(1)至(7)中任一項所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽之溶液之步驟;將前述溶液噴霧乾燥而使2-O-α-D-糖基-L-抗壞血酸金屬鹽為非晶質粉末之步驟。 (10) A method for producing an amorphous powder of 2-O-α-D-glycosyl-L-ascorbic acid metal salt, which comprises: (1) to ((1) to ( 7) The step of the 2-O-α-D-glycosyl-L-ascorbic acid metal salt solution according to any one of the above; spraying the solution to dry the 2-O-α-D-glycosyl-L- The step of ascorbic acid metal salt is an amorphous powder.
(11)一種抗氧化劑,其係含有下述通式(1)所示之2-O-α-D-糖基-L-抗壞血酸之金屬鹽而成者:
(式中,n係表示1至8之整數)。 (Where n is an integer from 1 to 8).
(12)如(11)所述之抗氧化劑,其中,2-O-α-D-糖基-L-抗壞血酸係2-O-α-D-葡吡喃糖基-L-抗壞血酸。 (12) The antioxidant according to (11), wherein the 2-O-α-D-glycosyl-L-ascorbic acid is 2-O-α-D-glucopyranosyl-L-ascorbic acid.
(13)如(11)或(12)所述之抗氧化劑,其中,2-O-α-D-糖基-L-抗壞血酸之金屬鹽係第一族金屬離子或第二族金屬離子之鹽。 (13) The antioxidant according to (11) or (12), wherein the metal salt of 2-O-α-D-glycosyl-L-ascorbic acid is a salt of a group 1 metal ion or a group 2 metal ion .
(14)如(11)至(13)中任一項所述之抗氧化劑,其中, 2-O-α-D-糖基-L-抗壞血酸之金屬鹽係鉀鹽或鎂鹽。 (14) The antioxidant according to any one of (11) to (13), wherein The metal salt of 2-O-α-D-glycosyl-L-ascorbic acid is a potassium salt or a magnesium salt.
(15)如(11)至(14)中任一項所述之抗氧化劑,其中,2-O-α-D-糖基-L-抗壞血酸之金屬鹽係非晶質粉末。 (15) The antioxidant according to any one of (11) to (14), wherein the metal salt of 2-O-α-D-glycosyl-L-ascorbic acid is an amorphous powder.
(16)一種皮膚外用劑,其係含有(1)至(7)中任一項所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽或(11)至(15)中任一項所述之抗氧化劑而成者。 (16) A skin external preparation containing the 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to any one of (1) to (7) or (11) to (15) Any one of the antioxidants described above.
(17)一種食品,其係含有(1)至(7)中任一項所述之2-O-α-D-糖基-L-抗壞血酸金屬鹽或(11)至(15)中任一項所述之抗氧化劑而成者。 (17) A food containing the 2-O-α-D-glycosyl-L-ascorbic acid metal salt according to any one of (1) to (7) or any one of (11) to (15) The antioxidants described in the item.
(18)一種含抗氧化劑之組成物,其係含有(11)至(15)中任一項所述之抗氧化劑、及欲防止氧化之成分而成之組成物,其中,前述抗氧化劑對前述欲防止氧化之成分之比率係0.1重量%至30重量%。 (18) An antioxidant-containing composition comprising the antioxidant according to any one of (11) to (15) and a component to be prevented from oxidation, wherein the antioxidant is The ratio of the component to be prevented from being oxidized is 0.1% by weight to 30% by weight.
本發明之一實施形態係提供2-O-α-D-糖基-L-抗壞血酸金屬鹽,其無論在固體狀態及液體狀態之任一狀態下皆具有高安定性且具有優異之保濕性。 One embodiment of the present invention provides 2-O-α-D-glycosyl-L-ascorbic acid metal salt, which has high stability and excellent moisturizing property in any of solid state and liquid state.
又,本發明之一實施形態係提供含有2-O-α-D-糖基-L-抗壞血酸金屬鹽而成之抗氧化劑。 Furthermore, one embodiment of the present invention provides an antioxidant containing a 2-O-α-D-glycosyl-L-ascorbic acid metal salt.
第1圖係2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg)(實施例1)之粉末X射線繞射圖。 FIG. 1 is a powder X-ray diffraction pattern of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg) (Example 1).
第2圖係2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽 (K)(實施例10)之粉末X射線繞射圖。 Figure 2 is 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K) A powder X-ray diffraction pattern of (Example 10).
第3圖係2-O-α-D-葡吡喃糖基-L-抗壞血酸(比較例1)之粉末X射線繞射圖。 Fig. 3 is a powder X-ray diffraction pattern of 2-O-α-D-glucopyranosyl-L-ascorbic acid (Comparative Example 1).
本發明包含複數個實施形態。關於一實施形態所使用及/或定義之用語,當沒有另外界定時,在其他全部的實施形態中視為具有相同意義。 The present invention includes a plurality of embodiments. The terms used and / or defined in one embodiment are considered to have the same meaning in all other embodiments unless otherwise defined.
<2-O-α-D-糖基-L-抗壞血酸> <2-O-α-D-glycosyl-L-ascorbic acid>
本發明之一實施形態中,2-O-α-D-糖基-L-抗壞血酸係指下述通式(1)所示之2-O-α-D-糖基-L-抗壞血酸之1種或該等之混合物:
(式中,n係表示1以上之整數)。 (In the formula, n is an integer of 1 or more.)
前述通式(1)之n意指與鍵結在L-抗壞血酸之2位的葡萄糖殘基之α位鍵結之糖(葡萄糖)的數為1以上之整數,較佳1至8或1至3,特佳係1。本發明之可為2-O-α-D-葡吡喃糖基-L-抗壞血酸(n=1)、2-O-α-D-麥芽糖基-L-抗壞
血酸(n=2)、2-O-α-D-麥芽三糖基-L-抗壞血酸(n=3)、2-O-α-D-麥芽四糖基-L-抗壞血酸(n=4)、2-O-α-D-麥芽五糖基-L-抗壞血酸(n=5)、2-O-α-D-麥芽六糖基-L-抗壞血酸(n=6)、2-O-α-D-麥芽七糖基-L-抗壞血酸(n=7)或2-O-α-D-麥芽八糖基-L-抗壞血酸(n=8)中之任一者或該等之混合物,但較佳係至少包含下述化學式(2)所示之2-O-α-D-葡吡喃糖基-L-抗壞血酸:
從保濕性更優異之點來看,2-O-α-D-糖基-L-抗壞血酸,較佳可列舉除了2-O-α-D-葡吡喃糖基-L-抗壞血酸之外,更含有2-O-α-D-麥芽糖基-L-抗壞血酸及/或2-O-α-D-麥芽三糖基-L-抗壞血酸。 From the viewpoint of more excellent moisturizing properties, 2-O-α-D-glycosyl-L-ascorbic acid is preferred, and in addition to 2-O-α-D-glucopyranosyl-L-ascorbic acid, It further contains 2-O-α-D-maltosyl-L-ascorbic acid and / or 2-O-α-D-maltotriosyl-L-ascorbic acid.
又,2-O-α-D-糖基-L-抗壞血酸可藉由公知方法,例如專利文獻1所記載之方法而製造。以下記載2-O-α-D-葡吡喃糖基-L-抗壞血酸之製造方法作為一例。 The 2-O-α-D-glycosyl-L-ascorbic acid can be produced by a known method, for example, the method described in Patent Document 1. A method for producing 2-O-α-D-glucopyranosyl-L-ascorbic acid is described below as an example.
(1)於含有L-抗壞血酸與α-葡萄糖基糖化合物之溶液,使糖基轉移酶作用,繼而使葡萄糖澱粉酶作用,而製 作含有2-O-α-D-葡吡喃糖基-L-抗壞血酸之溶液。 (1) In a solution containing L-ascorbic acid and an α-glucosyl sugar compound, the glycosyltransferase acts, and then the glucoamylase acts to prepare As a solution containing 2-O-α-D-glucopyranosyl-L-ascorbic acid.
(2)將含有2-O-α-D-葡吡喃糖基-L-抗壞血酸之溶液,使用離子交換樹脂等而精製,製造含有高純度之2-O-α-D-葡吡喃糖基-L-抗壞血酸之溶液。 (2) Refining a solution containing 2-O-α-D-glucopyranosyl-L-ascorbic acid using an ion exchange resin or the like to produce 2-O-α-D-glucopyranose with high purity -L-ascorbic acid solution.
(3)使2-O-α-D-葡吡喃糖基-L-抗壞血酸晶析,得到2-O-α-D-葡吡喃糖基-L-抗壞血酸。 (3) Crystallizing 2-O-α-D-glucopyranosyl-L-ascorbic acid to obtain 2-O-α-D-glucopyranosyl-L-ascorbic acid.
本發明中,可使用(2)之含有2-O-α-D-葡吡喃糖基-L-抗壞血酸之溶液而直接製造金屬鹽。 In the present invention, a metal salt can be directly produced using a solution containing 2-O-α-D-glucopyranosyl-L-ascorbic acid (2).
<2-O-α-D-糖基-L-抗壞血酸金屬鹽> <2-O-α-D-glycosyl-L-ascorbic acid metal salt>
可藉由使2-O-α-D-糖基-L-抗壞血酸、與金屬鹽反應而製造2-O-α-D-糖基-L-抗壞血酸金屬鹽。 The 2-O-α-D-glycosyl-L-ascorbic acid metal salt can be produced by reacting 2-O-α-D-glycosyl-L-ascorbic acid with a metal salt.
本發明之一實施形態中,2-O-α-D-糖基-L-抗壞血酸金屬鹽之金屬離子,可為選自由如鈉離子、鉀離子等第一族元素之金屬離子;如鎂離子、鈣離子等第二族元素之金屬離子;如鐵離子、銅離子等過渡金屬離子;及鋅離子、鋁離子等其他金屬離子所構成之群組之金屬離子或其組合。 In one embodiment of the present invention, the metal ion of the 2-O-α-D-glycosyl-L-ascorbic acid metal salt may be a metal ion selected from Group I elements such as sodium ion and potassium ion; for example, magnesium ion Metal ions of Group 2 elements such as calcium ions; transition metal ions such as iron ions and copper ions; and metal ions or a combination thereof composed of other metal ions such as zinc ions and aluminum ions.
本發明之一實施形態中,2-O-α-D-糖基-L-抗壞血酸金屬鹽之金屬離子至少含有1種第二族元素之金屬離子。較佳係含有鎂離子。該實施形態中,2-O-α-D-糖基-L-抗壞血酸金屬鹽之第二族元素之金屬離子對2-O-α-D-糖基-L-抗壞血酸之莫耳比可為0.01以上、0.05以上、或0.10以上,且可為0.50以下、0.30以下、或0.20以下,較佳係0.01至0.20之範圍。又,2-O-α-D-糖基-L-抗壞血酸金屬鹽含有鎂離子時,鎂離子對2-O-α-D-糖基-L-抗壞 血酸之莫耳比可為0.01以上、0.05以上、或0.10以上,且可為0.50以下、0.30以下、或0.20以下,較佳係0.01至0.20之範圍。 In one embodiment of the present invention, the metal ion of the 2-O-α-D-glycosyl-L-ascorbic acid metal salt contains at least one metal ion of a second group element. Preferably, it contains magnesium ion. In this embodiment, the molar ratio of the metal ion of the second group element of the 2-O-α-D-glycosyl-L-ascorbic acid metal salt to the 2-O-α-D-glycosyl-L-ascorbic acid may be 0.01 or more, 0.05 or more, or 0.10 or more, and may be 0.50 or less, 0.30 or less, or 0.20 or less, preferably in the range of 0.01 to 0.20. When the 2-O-α-D-glycosyl-L-ascorbic acid metal salt contains magnesium ions, the magnesium ions are resistant to 2-O-α-D-glycosyl-L- The molar ratio of blood acid may be 0.01 or more, 0.05 or more, or 0.10 or more, and may be 0.50 or less, 0.30 or less, or 0.20 or less, preferably in the range of 0.01 to 0.20.
與2-O-α-D-糖基-L-抗壞血酸反應之金屬鹽,可列舉:氫氧化鎂、氫氧化鈉、氫氧化鉀、氫氧化鈣、氯化鎂、氯化鈉、氯化鉀、氯化鈣、硫酸鎂、硫酸鈉、硫酸鉀、硝酸鈉、碳酸鈉、碳酸氫鈉、碳酸鉀、磷酸鈉等。由於反應所致之副產物為水,故特佳係氫氧化鎂、氫氧化鈉、氫氧化鉀、氫氧化鈣等氫氧化金屬鹽。 Examples of metal salts that react with 2-O-α-D-glycosyl-L-ascorbic acid include magnesium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium chloride, sodium chloride, potassium chloride, and chlorine. Calcium, magnesium sulfate, sodium sulfate, potassium sulfate, sodium nitrate, sodium carbonate, sodium bicarbonate, potassium carbonate, sodium phosphate, etc. Since the by-product of the reaction is water, particularly preferred are metal hydroxides such as magnesium hydroxide, sodium hydroxide, potassium hydroxide, and calcium hydroxide.
<2-O-α-D-糖基-L-抗壞血酸金屬鹽之粉末之製造方法> <Method for manufacturing 2-O-α-D-glycosyl-L-ascorbic acid metal powder>
可藉由包括下述步驟之方法來製造2-O-α-D-糖基-L-抗壞血酸金屬鹽之非晶質粉末:製作在溶劑中溶解有前述2-O-α-D-糖基-L-抗壞血酸金屬鹽之溶液之步驟;以及將前述溶液噴霧乾燥而使2-O-α-D-糖基-L-抗壞血酸金屬鹽為非晶質粉末之步驟。 An amorphous powder of 2-O-α-D-glycosyl-L-ascorbic acid metal salt can be produced by a method including the following steps: making the 2-O-α-D-glycosyl group dissolved in a solvent -A step of a solution of the metal salt of L-ascorbic acid; and a step of spray-drying the aforementioned solution to make the 2-O-α-D-glycosyl-L-ascorbic acid metal salt an amorphous powder.
前述溶劑只要是溶解2-O-α-D-糖基-L-抗壞血酸金屬鹽者,即可自由地使用公知溶劑,但較佳係水及/或醇,特佳係水。前述醇較佳係乙醇。 The solvent may be any known solvent as long as it dissolves 2-O-α-D-glycosyl-L-ascorbic acid metal salt, but water and / or alcohol is preferred, and water is particularly preferred. The alcohol is preferably ethanol.
前述噴霧乾燥可使用例如噴霧乾燥機而進行。噴霧乾燥,較佳可列舉使噴霧乾燥機之入口溫度為140至180℃時進行。低於140℃之低溫時,可能無法充分蒸發溶劑,故會有無法得到乾燥粉末之虞。另一方面,高於180℃之高溫時,於步驟中會有6-醯基-2-O-α-D-糖基-L-抗壞血酸 及2-O-α-D-糖基-L-抗壞血酸分解或揮發之虞。又,較佳可列舉噴霧乾燥機之出口溫度為50至100℃時進行。 The spray drying can be performed using, for example, a spray dryer. Spray drying is preferably performed when the inlet temperature of the spray dryer is 140 to 180 ° C. When the temperature is lower than 140 ° C, the solvent may not be sufficiently evaporated, so there is a possibility that a dry powder cannot be obtained. On the other hand, when the temperature is higher than 180 ° C, there will be 6-fluorenyl-2-O-α-D-glycosyl-L-ascorbic acid in the step. And 2-O-α-D-glycosyl-L-ascorbic acid may be decomposed or volatile. Moreover, it is preferable to carry out when the exit temperature of a spray dryer is 50-100 degreeC.
本發明之一實施形態中,2-O-α-D-糖基-L-抗壞血酸金屬鹽係不僅其本身安定並且具有使其他成分安定化之效果。亦即,2-O-α-D-糖基-L-抗壞血酸金屬鹽係有用作為安定化劑。 In one embodiment of the present invention, the 2-O-α-D-glycosyl-L-ascorbic acid metal salt system not only stabilizes itself but also has the effect of stabilizing other components. That is, a 2-O-α-D-glycosyl-L-ascorbic acid metal salt system is useful as a stabilizer.
安定化劑係意指為了防止其他成分因熱、光、氧等而引起分解、劣化、變質等而添加之添加劑。安定化劑可為用來防止氧化抗性弱之化合物被氧化、分解之抗氧化劑。 The stabilizer refers to an additive added to prevent decomposition, deterioration, deterioration, and the like of other components due to heat, light, and oxygen. The stabilizer may be an antioxidant used to prevent a compound having weak oxidation resistance from being oxidized and decomposed.
本發明之一實施形態中,藉由抗氧化劑防止氧化之成分無特別限定,可例示:維生素A、維生素C、維生素E等維生素類;綠原酸、單寧類、兒茶素類、槲皮素等多酚類;胡蘿蔔素、葉黃素等類胡蘿蔔素等。 In one embodiment of the present invention, the ingredients for preventing oxidation by antioxidants are not particularly limited, and examples thereof include vitamins such as vitamin A, vitamin C, and vitamin E; chlorogenic acids, tannins, catechins, and quercetin Polyphenols, such as carotene; carotenoids, such as carotene and lutein.
本發明之一實施形態中,為了得到充分的安定效果,相對於欲予以安定化之成分,安定化劑宜添加0.1重量%以上、1重量%以上、2重量%以上、5重量%以上、或10重量%以上。2-O-α-D-糖基-L-抗壞血酸金屬鹽即使只有些微的量仍具有高安定效果,故可依期望而相對於欲予以安定化之成分,以30重量%以下、20重量%以下、10重量%以下、5重量%以下、2重量%以下使用。 In one embodiment of the present invention, in order to obtain a sufficient stabilization effect, it is preferable to add a stabilizer to the component to be stabilized by 0.1% by weight or more, 1% by weight or more, 2% by weight or more, 5% by weight or more, or 10% by weight or more. 2-O-α-D-glycosyl-L-ascorbic acid metal salt has a high stabilization effect even in a slight amount, so it can be 30% by weight or less and 20% by weight relative to the component to be stabilized as desired. Use below 10% by weight, below 5% by weight, below 2% by weight.
本發明之一實施形態中,2-O-α-D-糖基-L-抗壞血酸金屬鹽對人類等動物為無害,可添加於食品、皮膚外用劑等。2-O-α-D-糖基-L-抗壞血酸金屬鹽可單獨使用、或與其他成分併用而作為飲食品、皮膚外用劑等來使 用。 In one embodiment of the present invention, the 2-O-α-D-glycosyl-L-ascorbic acid metal salt is not harmful to animals such as humans, and can be added to foods, skin external preparations, and the like. 2-O-α-D-glycosyl-L-ascorbic acid metal salt can be used alone or in combination with other ingredients as food or drink, skin external preparation, etc. use.
皮膚外用劑係意指應用於外皮之組成物,包含例如化妝品、醫藥品、準藥品。外皮包含毛髮及指甲。 The external preparation for skin means a composition applied to the outer skin, and includes, for example, cosmetics, pharmaceuticals, and quasi-drugs. The outer skin contains hair and nails.
皮膚外用劑,可因應使用目的、製劑特性及使用形態而適當地選擇並應用一般於皮膚外用劑調製時所使用之公知之基劑、載體等。又,可依需要而併用其他成分,例如,界面活性劑、皮膚吸收促進劑、抗氧化劑、補助劑、紫外線吸收劑、增稠劑、增量劑、安定劑、著色劑、附著香味劑、防腐劑、防黴劑等。 The external preparation for skin can be appropriately selected and applied in accordance with the purpose of use, the characteristics of the preparation, and the use form, and known bases, carriers, and the like that are generally used in the preparation of external preparations for skin. In addition, other ingredients may be used in combination, such as a surfactant, a skin absorption enhancer, an antioxidant, a supplement, an ultraviolet absorber, a thickener, an extender, a stabilizer, a coloring agent, a fragrance attaching agent, and a preservative. Agents, mold inhibitors, etc.
皮膚外用劑可依使用目的及使用形態等期望而適當地選擇並調製作為軟膏劑、霜劑、噴霧劑、洗劑、粉劑、凝膠劑、溶膠劑、氣溶膠劑、泥罨劑、貼布劑、擦劑、乳液、化妝水、美容液、面膜劑、底妝、粉底等劑形。 The external preparations for the skin can be appropriately selected and prepared as an ointment, cream, spray, lotion, powder, gel, sol, aerosol, lozenge, patch, etc. according to the intended use and the use form. Agents, lotions, lotions, lotions, beauty liquids, masks, base makeup, foundations and other dosage forms.
本發明之一實施形態中,相對於皮膚外用劑整體,皮膚外用劑係含有0.001至50重量%、或0.01至20重量%,較佳係0.1重量%至10重量%之2-O-α-D-糖基-L-抗壞血酸金屬鹽。 In one embodiment of the present invention, the skin external preparation contains 0.001 to 50% by weight, or 0.01 to 20% by weight, and preferably 2-O-α- D-glycosyl-L-ascorbic acid metal salt.
以下例子中,更詳細說明本發明,但本發明不限於此。 In the following examples, the present invention will be described in more detail, but the present invention is not limited thereto.
本發明中之其他用語及概念係依據該領域中慣用之用語的意義者,為了實施本發明而使用之各種技術,除了特別明示其出處之技術以外,只要是該技術領域人員即可依據公知文獻等而容易且確實地實施。又,各種分析等係應 用所使用之析機器或試劑、套組的操作說明書、目錄等所記載之方法而進行。 Other terms and concepts in the present invention are based on the meanings of terms commonly used in the field. Various technologies used in order to implement the present invention. Except for the technology that clearly indicates the source, as long as it is a person in the technical field, it can be based on well-known documents. It is easy and reliable to implement. Also, various analysis It is carried out by the methods described in the operating instructions, catalogues, etc. of the analysis equipment or reagents used, the kits.
再者,本說明書中所引用之先前技術文獻、專利公報及專利申請說明書中之記載內容,係參照而作為本發明之記載內容。 In addition, the contents described in the prior art documents, patent publications, and patent application specifications cited in this specification are the contents of the present invention by reference.
(實施例1) (Example 1)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg)
(1)2-O-α-D-葡吡喃糖基-L-抗壞血酸之合成 (1) Synthesis of 2-O-α-D-glucopyranosyl-L-ascorbic acid
於水1000g中添加液化澱粉125g及L-抗壞血酸50g並使其溶解,將pH調整為5.0。於其中添加環麥芽糊精葡聚糖轉移酶酵素製劑(Toruzyme3.0L,Novozymes公司製)20g,在50℃反應48小時,而得到含有2-O-α-D-葡吡喃糖基-L-抗壞血酸、2-O-α-麥芽糖基-L-抗壞血酸、2-O-α-麥芽三糖基-L-抗壞血酸、2-O-α-麥芽四糖基-L-抗壞血酸等2-O-α-D-糖基-L-抗壞血酸之反應液。 To 1000 g of water, 125 g of liquefied starch and 50 g of L-ascorbic acid were added and dissolved, and the pH was adjusted to 5.0. 20 g of a cyclomaltodextrin dextran transferase enzyme preparation (Toruzyme 3.0L, manufactured by Novozymes) was added thereto, and the mixture was reacted at 50 ° C. for 48 hours to obtain 2-O-α-D-glucopyranosyl- L-ascorbic acid, 2-O-α-maltosyl-L-ascorbic acid, 2-O-α-maltotriosyl-L-ascorbic acid, 2-O-α-maltotetraosyl-L-ascorbic acid, etc. 2 -O-α-D-glycosyl-L-ascorbic acid reaction solution.
將所得之反應液加熱而使酵素去活性化並停止反應後,添加葡萄糖澱粉酶酵素製劑(GLUCZYME AF6,Amano Enzyme股份有限公司製)1.5g,在50℃反應16小時,而得到含有2-O-α-D-葡吡喃糖基-L-抗壞血酸之反應液。反應後,加熱而使酵素去活性化並停止反應。 After heating the obtained reaction solution to deactivate the enzyme and stop the reaction, 1.5 g of a glucoamylase enzyme preparation (GLUCZYME AF6, manufactured by Amano Enzyme Co., Ltd.) was added and reacted at 50 ° C for 16 hours to obtain 2-O -α-D-glucopyranosyl-L-ascorbic acid reaction solution. After the reaction, the enzyme is heated to deactivate the enzyme and stop the reaction.
(2)2-O-α-D-葡吡喃糖基-L-抗壞血酸之精製 (2) Purification of 2-O-α-D-glucopyranosyl-L-ascorbic acid
將所得之反應液加熱而使酵素去活性化並停止反應 後,添加活性碳並脫色、過濾。將濾液於填充有H型陽離子交換樹脂之管柱通液,去除金屬離子後,於填充有OH型陰離子交換樹脂之管柱通液而使2-O-α-D-葡吡喃糖基-L-抗壞血酸吸附。將吸附有2-O-α-D-葡吡喃糖基-L-抗壞血酸之陰離子交換樹脂水洗而去除未反應糖類後,將0.1N氫氧化鈉通液,而溶析出2-O-α-D-葡吡喃糖基-L-抗壞血酸。進一步,將該溶析液於填充有H型陽離子交換樹脂之管柱通液,得到金屬離子經去除之2-O-α-D-葡吡喃糖基-L-抗壞血酸之精製液。 Heating the obtained reaction solution to deactivate the enzyme and stop the reaction After that, activated carbon was added, decolorized, and filtered. The filtrate was passed through a column filled with an H-type cation exchange resin to remove metal ions, and then passed through a column filled with an OH-type anion exchange resin to pass 2-O-α-D-glucopyranosyl- L-ascorbic acid adsorption. After washing the anion exchange resin to which 2-O-α-D-glucopyranosyl-L-ascorbic acid has been adsorbed to remove unreacted saccharides, 0.1N sodium hydroxide is passed through the liquid to precipitate 2-O-α- D-glucopyranosyl-L-ascorbic acid. Further, the eluate was passed through a column filled with an H-type cation exchange resin to obtain a purified solution of 2-O-α-D-glucopyranosyl-L-ascorbic acid from which metal ions were removed.
(3)2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽之合成 (3) Synthesis of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt
相對於精製液所含有之2-O-α-D-葡吡喃糖基-L-抗壞血酸,添加0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鉀,在40℃攪拌1小時,而得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg)之水溶液。 Add 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of potassium hydroxide to 2-O-α-D-glucopyranosyl-L-ascorbic acid contained in the purified solution, and stir at 40 ° C for 1 hour. To obtain an aqueous solution of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg).
(4)2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽之噴霧乾燥 (4) Spray drying of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt
將2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽之水溶液加熱減壓濃縮至固體成分15%左右之後,添加活性碳進行脫色精製,過濾。將濾液使用噴霧乾燥機(日本BUCHI公司製,B-290)以入口溫度160℃、出口溫度75℃進行噴霧乾燥,而得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg)之粉末48g。 The 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt solution was heated under reduced pressure and concentrated to about 15% solid content, and then activated carbon was added to decolorize and refine it, and then filtered. The filtrate was spray-dried using a spray dryer (manufactured by BUCHI Corporation, B-290) at an inlet temperature of 160 ° C and an outlet temperature of 75 ° C to obtain 2-O-α-D-glucopyranosyl-L-ascorbic acid metal 48g of salt (K, Mg) powder.
(實施例2) (Example 2)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg)
除了使用0.01莫耳當量之氫氧化鎂與0.98莫耳當量之氫氧化鉀代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鉀以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg)之粉末。 Except that 0.01 mol equivalent of magnesium hydroxide and 0.98 mol equivalent of potassium hydroxide are used in place of the 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of potassium hydroxide described in Example 1 (3). In the same manner as in Example 1, a powder of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg) was obtained.
(實施例3) (Example 3)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg)
除了使用0.10莫耳當量之氫氧化鎂與0.80莫耳當量之氫氧化鉀代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鉀以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg)之粉末。 Except that 0.10 mol equivalent of magnesium hydroxide and 0.80 mol equivalent of potassium hydroxide are used in place of the 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of potassium hydroxide described in Example 1 (3). In the same manner as in Example 1, a powder of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg) was obtained.
(實施例4) (Example 4)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg)
除了使用0.20莫耳當量之氫氧化鎂與0.60莫耳當量之氫氧化鉀代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鉀以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg)之粉末。 Except using 0.20 mol equivalent of magnesium hydroxide and 0.60 mol equivalent of potassium hydroxide instead of 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of potassium hydroxide described in Example 1 (3), and In the same manner as in Example 1, a powder of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg) was obtained.
(實施例5) (Example 5)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg)
除了使用0.30莫耳當量之氫氧化鎂與0.40莫耳當量之氫氧化鉀代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂 與0.90莫耳當量之氫氧化鉀以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg)之粉末。 Instead of using 0.30 mol equivalent of magnesium hydroxide and 0.40 mol equivalent of potassium hydroxide instead of the 0.05 mol equivalent of magnesium hydroxide described in Example 1 (3) A powder of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg) was obtained in the same manner as in Example 1 except for 0.90 mol equivalent of potassium hydroxide.
(實施例6) (Example 6)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(Mg) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (Mg)
除了使用0.50莫耳當量之氫氧化鎂代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鈉以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(Mg)之粉末。 2-O was obtained in the same manner as in Example 1 except that 0.50 mol equivalent of magnesium hydroxide was used instead of 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of sodium hydroxide described in Example 1 (3). -α-D-glucopyranosyl-L-ascorbic acid metal salt (Mg) powder.
(實施例7) (Example 7)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(Na、Mg) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (Na, Mg)
除了使用0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鈉代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鉀以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(Na、Mg)之粉末50g。 Except using 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of sodium hydroxide instead of 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of potassium hydroxide described in Example 1 (3), and In the same manner as in Example 1, 50 g of a powder of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (Na, Mg) was obtained.
(實施例8) (Example 8)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(Ca、Mg) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (Ca, Mg)
除了使用0.05莫耳當量之氫氧化鎂與0.45莫耳當量之氫氧化鈣代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鉀以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(Ca、Mg)之粉末52g。 Except using 0.05 mol equivalent of magnesium hydroxide and 0.45 mol equivalent of calcium hydroxide instead of the 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of potassium hydroxide described in Example 1 (3), and In the same manner as in Example 1, 52 g of powder of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (Ca, Mg) was obtained.
(實施例9) (Example 9)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(Na) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (Na)
除了使用1莫耳當量之氫氧化鈉代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鉀以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(Na)之粉末46g。 2-O was obtained in the same manner as in Example 1 except that 1 mol equivalent of sodium hydroxide was used instead of the 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of potassium hydroxide described in Example 1 (3). 46g of -α-D-glucopyranosyl-L-ascorbic acid metal salt (Na).
(實施例10) (Example 10)
2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K) 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K)
除了使用1莫耳當量之氫氧化鉀代替實施例1(3)所述之0.05莫耳當量之氫氧化鎂與0.90莫耳當量之氫氧化鉀以外,以與實施例1同樣方式得到2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K)之粉末47g。 2-O was obtained in the same manner as in Example 1 except that 1 mol equivalent of potassium hydroxide was used instead of the 0.05 mol equivalent of magnesium hydroxide and 0.90 mol equivalent of potassium hydroxide described in Example 1 (3). 47g of -α-D-glucopyranosyl-L-ascorbic acid metal salt (K) powder.
(比較例1) (Comparative example 1)
2-O-α-D-葡吡喃糖基-L-抗壞血酸之結晶粉末 2-O-α-D-glucopyranosyl-L-ascorbic acid
將直到實施例1(2)為止皆同樣地操作而得之精製液在50℃進行加熱減壓濃縮,濃縮至固體成分60%左右之後,將水溶液冷卻至10℃而使結晶析出。將析出物過濾而回收,以少量的水洗淨後,將析出物減壓乾燥,而得到2-O-α-D-葡吡喃糖基-L-抗壞血酸之結晶粉末17g。 The purified solution obtained in the same manner as in Example 1 (2) was concentrated under heating and reduced pressure at 50 ° C, and concentrated to about 60% of the solid content, and then the aqueous solution was cooled to 10 ° C to precipitate crystals. The precipitate was collected by filtration and washed with a small amount of water. The precipitate was dried under reduced pressure to obtain 17 g of 2-O-α-D-glucopyranosyl-L-ascorbic acid crystalline powder.
(比較例2) (Comparative example 2)
2-O-α-D-葡吡喃糖基-L-抗壞血酸之非晶質粉末 2-O-α-D-glucopyranosyl-L-ascorbic acid amorphous powder
將直到實施例1之步驟(2)為止皆同樣地操作而得之精製液在50℃進行加熱減壓濃縮,濃縮至固體成分15%左右之後,添加活性碳進行脫色精製,過濾。將濾液使用噴霧乾燥機(日本BUCHI公司製,B-290)以入口溫度160℃、出 口溫度75℃進行噴霧乾燥,而得到2-O-α-D-葡吡喃糖基-L-抗壞血酸之非晶質粉末41g。 The purified solution obtained in the same manner as in step (2) of Example 1 was concentrated under heating and reduced pressure at 50 ° C., and concentrated to about 15% of solid content, and then activated carbon was added for decolorization and purification, and filtered. The filtrate was spray-dried (manufactured by BUCHI, Japan, B-290) at an inlet temperature of 160 ° C, The mouth temperature was 75 ° C and spray-dried to obtain 41 g of 2-O-α-D-glucopyranosyl-L-ascorbic acid amorphous powder.
<保存安定性之評估> <Assessment of preservation stability>
粉末之安定性 Stability of powder
分別將實施例1至10及比較例1所得之2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽或2-O-α-D-葡吡喃糖基-L-抗壞血酸之結晶粉末5g放入密閉容器,在40℃環境下保存250小時而進行安定性試驗。安定性係將試驗後之粉末由下述條件之高效液相層析(HPLC)法定量分析,計算出殘留率而評估。將結果示於表1。HPLC法係使用Waters公司製高效液相層析裝置,管柱係使用Shodex Asahipak NH2P-50 4E 4.6×250mm。(管柱溫度:40℃,移動相:乙腈/0.1%磷酸緩衝液=60/40,流速:0.7mL/分鐘,波長:254nm) The 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt or 2-O-α-D-glucopyranosyl-L-ascorbic acid obtained in Examples 1 to 10 and Comparative Example 1, respectively 5 g of the crystal powder was placed in a closed container and stored in a 40 ° C environment for 250 hours to perform a stability test. The stability is determined by quantitatively analyzing the powder after the test by a high-performance liquid chromatography (HPLC) method under the following conditions, and calculating the residual rate. The results are shown in Table 1. The HPLC method uses a high-performance liquid chromatography device manufactured by Waters, and the column system uses Shodex Asahipak NH2P-50 4E 4.6 × 250 mm. (Column temperature: 40 ° C, mobile phase: acetonitrile / 0.1% phosphate buffer = 60/40, flow rate: 0.7mL / min, wavelength: 254nm)
水溶液之安定性 Stability of aqueous solution
分別使實施例1至10、比較例1所得之2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽或2-O-α-D-葡吡喃糖基-L-抗壞血酸1g溶解於水20g中而形成水溶液,將該水溶液放入密閉容器,在40℃環境下保存250小時而進行安定性試驗。安定性係將試驗後之水溶液由HPLC法定量分析,計算出殘留率而評估。將結果示於表1。 The 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt or 2-O-α-D-glucopyranosyl-L-ascorbic acid obtained in Examples 1 to 10 and Comparative Example 1 were respectively used. 1 g was dissolved in 20 g of water to form an aqueous solution. This aqueous solution was placed in a closed container and stored in a 40 ° C. environment for 250 hours to perform a stability test. The stability is evaluated by quantitative analysis of the aqueous solution after the test by HPLC, and calculating the residual rate. The results are shown in Table 1.
<保濕性之評估方法> <Evaluation method of moisturizing property>
調整各生成物之30重量%水溶液,將水溶液10g放入45mm之玻璃盤,將該盤放入溫度25℃、濕度35%之恆溫/恆濕器,保持24小時。測定保持後之各生成物之重量, 計算出重量殘留率(%)。將結果示於表1。重量殘留率越高則表示保濕力越高。 Adjust the 30% by weight aqueous solution of each product, and put 10g of the aqueous solution in A 45mm glass plate was placed in a thermostat / humidifier at a temperature of 25 ° C and a humidity of 35% and held for 24 hours. The weight of each product after the retention was measured, and the weight residual ratio (%) was calculated. The results are shown in Table 1. The higher the weight residual rate, the higher the moisturizing power.
<粉末X射線繞射裝置> <Powder X-ray Diffraction Device>
使用將CuK α線作為X射線源之粉末X射線繞射裝置(理學電氣公司製,RINT2200),以管電壓為40kV、管電流為20mA、掃描範圍(2 θ)為5°至40°、發散狹縫為1/2°、散射狹縫為1/2°、受光狹縫為0.15mm、取樣寬度為0.02°、掃描速度為4°/分鐘之條件進行測定。將實施例1之2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K、Mg)之峰示於第1圖, 將實施例10之2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽(K)之峰示於第2圖,將比較例1之2-O-α-D-葡吡喃糖基-L-抗壞血酸之峰示於第3圖。 A powder X-ray diffraction device (RINT2200, manufactured by Rigaku Electric Co., Ltd.) using CuK α rays as an X-ray source was used, with a tube voltage of 40 kV, a tube current of 20 mA, a scanning range (2 θ) of 5 ° to 40 °, and divergence. The measurement was performed under conditions of a slit of 1/2 °, a scattering slit of 1/2 °, a light receiving slit of 0.15 mm, a sampling width of 0.02 °, and a scanning speed of 4 ° / minute. The peak of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K, Mg) in Example 1 is shown in FIG. 1, The peak of 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt (K) in Example 10 is shown in FIG. 2, and the 2-O-α-D-glucopyridine in Comparative Example 1 is shown in FIG. 2. The peak of glycosyl-L-ascorbic acid is shown in FIG. 3.
粉末X射線繞射之峰係顯示實施例1及10之2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽為非晶質,而比較例1之2-O-α-D-葡吡喃糖基-L-抗壞血酸為結晶。咸認以與實施例1及10同樣方法粉末化之實施例2至9及比較例2之固體亦為非晶質。 The peaks of powder X-ray diffraction show that 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salts of Examples 1 and 10 are amorphous, while that of Comparative Example 1 2-O-α- D-glucopyranosyl-L-ascorbic acid is crystalline. It is recognized that the solids of Examples 2 to 9 and Comparative Example 2 which were powdered in the same manner as in Examples 1 and 10 were also amorphous.
令人驚訝的是實施例1至8之2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽即使在固體狀態為非晶質,卻仍顯示與結晶性之2-O-α-D-葡吡喃糖基-L-抗壞血酸同等程度之安定性。又,2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽雖然在金屬離子含有第二族元素之金屬離子時顯示高安定性與優異之保濕性,但意外地,與金屬離子僅為第二族元素之金屬離子時相比,金屬離子為第二族元素之金屬離子與其他金屬離子之混合時顯示更優異之效果。 Surprisingly, the 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt of Examples 1 to 8 still showed 2-O- with crystallinity even though it was amorphous in the solid state. Alpha-D-glucopyranosyl-L-ascorbic acid is equally stable. In addition, although 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt exhibits high stability and excellent moisturizing property when the metal ion contains a metal ion of a second group element, it is unexpectedly associated with metal Compared with the case where the ions are only metal ions of the second group element, the metal ions having the second group element and other metal ions have a more excellent effect.
<混合製劑之製作> <Preparation of mixed preparations>
將實施例6、10及比較例1、2所製作之各粉末0.5g、與L-抗壞血酸之粉末5g放入110ml試樣瓶,以混合旋轉器進行粉末混合,製作L-抗壞血酸混合製劑。 0.5 g of each powder prepared in Examples 6, 10 and Comparative Examples 1 and 2 and 5 g of powder of L-ascorbic acid were put into a 110 ml sample bottle, and the powder was mixed with a mixing rotator to prepare an L-ascorbic acid mixed preparation.
除了將調製例1之L-抗壞血酸換成表沒食子兒茶素-3-沒食子酸酯(EGCG)(Sunphenon EGCG-OP,太陽化學股份有 限公司製)以外,同樣地操作,製作含有EGCG之混合製劑。 In addition to replacing L-ascorbic acid in Preparation Example 1 with epigallocatechin-3-gallate (EGCG) (Sunphenon EGCG-OP, Sun Chemical Co., Ltd. has Co., Ltd.) was manufactured in the same manner to prepare a mixed preparation containing EGCG.
除了將調製例1之L-抗壞血酸換成α-生育酚(Vitacoat E-70 α:α-生育酚含有率70%,橫濱油脂工業股份有限公司製)以外,同樣地操作,製作含有α-生育酚之混合製劑。 Except changing L-ascorbic acid in Preparation Example 1 to α-tocopherol (Vitacoat E-70 α: α-tocopherol content rate of 70%, manufactured by Yokohama Oils and Fats Industry Co., Ltd.), the same procedure was performed to produce α-tocopherol. Mixed formulation of phenol.
除了將調製例1之L-抗壞血酸換成槲皮素以外,同樣地操作,製作含有槲皮素之混合製劑。 A mixed preparation containing quercetin was prepared in the same manner except that L-ascorbic acid in Preparation Example 1 was replaced with quercetin.
相對於L-抗壞血酸之粉末5g,將實施例10所製作之粉末0.1g、0.25g、0.5g、1.0g、1.5g、2.5g、5.0g以與調製例1同樣方式進行粉末混合,製作各組成之L-抗壞血酸混合製劑。 0.1 g, 0.25 g, 0.5 g, 1.0 g, 1.5 g, 2.5 g, and 5.0 g of the powder prepared in Example 10 were mixed with 5 g of the powder of L-ascorbic acid in the same manner as in Preparation Example 1 to prepare each powder. Composition of L-ascorbic acid mixed preparation.
除了將調製例5之L-抗壞血酸換成EGCG以外,同樣地操作,製作各組成之含有EGCG之混合製劑。 A mixed preparation containing EGCG of each composition was prepared in the same manner except that L-ascorbic acid in Preparation Example 5 was replaced with EGCG.
<保存安定性之評估> <Assessment of preservation stability>
將各調製例所得之各種混合製劑5g放入容器,在60℃環境下保存500小時而進行安定性試驗。安定性係將粉末所含之L-抗壞血酸、EGCG、α-生育酚及槲皮素由下述條件之高效液相層析(HPLC)法定量分析,計算出殘留率而評估。又,一併實施分別將L-抗壞血酸、EGCG、α-生育酚及槲皮素5g放入容器,同樣地進行安定性試驗,作為無安定劑之例。將500小時後之殘留率之結果示於下述表1 及表2。HPLC法係使用Waters公司製高效液相層析裝置,管柱係使用COSMOSIL 5C18-MS-II 4.6×250mm。測定係針對各組成物,以下述條件測定。 5 g of various mixed preparations obtained in each of the preparation examples were put into a container, and stored in a 60 ° C. environment for 500 hours to perform a stability test. The stability was evaluated by quantitatively analyzing L-ascorbic acid, EGCG, α-tocopherol, and quercetin contained in the powder by a high-performance liquid chromatography (HPLC) method under the following conditions, and calculating the residual rate. In addition, 5 g of L-ascorbic acid, EGCG, α-tocopherol, and quercetin were put into a container, and a stability test was performed in the same manner as an example of no stabilizer. The results of the residual rate after 500 hours are shown in Table 1 below. And Table 2. The HPLC method uses a high-performance liquid chromatography device manufactured by Waters, and the column system uses COSMOSIL 5C18-MS-II 4.6 × 250mm. The measurement is performed for each composition under the following conditions.
L-抗壞血酸(管柱溫度:40℃,移動相:0.3%乙酸水溶液,流速:1mL/分鐘,測定波長:230nm) L-ascorbic acid (column temperature: 40 ° C, mobile phase: 0.3% acetic acid aqueous solution, flow rate: 1 mL / min, measurement wavelength: 230 nm)
EGCG(管柱溫度:40℃,移動相:乙腈/0.1%乙酸水溶液=10/90,流速:1mL/分鐘,測定波長230nm) EGCG (column temperature: 40 ° C, mobile phase: acetonitrile / 0.1% acetic acid aqueous solution = 10/90, flow rate: 1mL / min, measurement wavelength 230nm)
α-生育酚(管柱溫度:30℃,移動相:甲醇/水=90/10,流速1mL/分鐘,測定波長295nm) α-Tocopherol (column temperature: 30 ° C, mobile phase: methanol / water = 90/10, flow rate 1mL / min, measurement wavelength 295nm)
槲皮素(管柱溫度:40℃,移動相:乙腈/0.01%乙酸水溶液=20/80,流速0.5mL/分鐘,測定波長:254nm) Quercetin (column temperature: 40 ° C, mobile phase: acetonitrile / 0.01% acetic acid aqueous solution = 20/80, flow rate 0.5mL / min, measurement wavelength: 254nm)
實施例6及10之2-O-α-D-葡萄糖基-L-抗壞血酸金屬鹽對於L-抗壞血酸、EGCG、α-生育酚及槲皮素之任一者皆顯示高安定化效果。由調整例5及6得知,2-O-α-D-葡萄糖基-L-抗壞血酸金屬鹽對於安定化對象即使只有少量的2重量%仍顯示高安定化效果,5重量%至10重量%可得充分之安定化效果。此結果,令人驚訝的是2-O-α-D-葡萄糖基-L-抗壞血酸金屬鹽之安定化效果係超出顯示由代替其他成分而被分解之作用所預想的效果。 The 2-O-α-D-glucosyl-L-ascorbic acid metal salt of Examples 6 and 10 showed a high stabilization effect on any of L-ascorbic acid, EGCG, α-tocopherol, and quercetin. It is known from the adjustment examples 5 and 6 that the 2-O-α-D-glucosyl-L-ascorbic acid metal salt shows a high stabilization effect even if only a small amount of 2% by weight is stabilized, 5 to 10% by weight A sufficient stabilization effect can be obtained. As a result, it was surprising that the stabilization effect of the 2-O-α-D-glucosyl-L-ascorbic acid metal salt exceeded the effect expected from the effect of decomposing by replacing other components.
本發明之2-O-α-D-葡吡喃糖基-L-抗壞血酸金屬鹽,係特別有用於化妝品等皮膚外用劑。 The 2-O-α-D-glucopyranosyl-L-ascorbic acid metal salt of the present invention is particularly useful for external skin preparations such as cosmetics.
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JP3290490B2 (en) * | 1993-01-25 | 2002-06-10 | 株式会社林原生物化学研究所 | Metal salt of ascorbic acid-2-O-α-glucoside and pharmaceutical use thereof |
AU757681B2 (en) * | 1998-05-15 | 2003-02-27 | Showa Denko Kabushiki Kaisha | Preventives/remedies for skin diseases |
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