JPH03190891A - Maltitol aliphatic ether - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (A is residue produced by removing n-OH groups from maltitol; R<1> and R<2> are H or 1-20C alkyl; n is 1 or 2). EXAMPLE:Maltitol monomyristyl ether. USE:A surfactant to be compounded to drugs, quasi-drugs and cosmetics. It is chemically stable and has low stimulation to the skin and eye. PREPARATION:The objective compound can be produced by dissolving 4-O-alpha-D- glucopyranol-sorbitol of formula II in a non-aqueous solvent such as DMF, adding an alkyl derivative of formula III (X is halogen, trimethylammonium bromide or OH) and reacting at 50-130 deg.C in the presence of a catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a maltitol aliphatic ether represented by the general formula (I), more specifically, a maltitol aliphatic ether that is chemically stable,
This invention relates to maltitol aliphatic ether, which is a novel surfactant that has extremely low irritation to the skin and eyes and can be incorporated into pharmaceuticals, quasi-drugs, and cosmetics.

[Prior Art] Nonionic surfactants have conventionally been used in many external skin preparations for purposes such as emulsification, solubilization, and dispersion.

Commonly used nonionic surfactants include glycerin fatty acid ester, sorbitan fatty acid ester, sorbitol fatty acid ester, sea monosaccharide fatty acid ester,
Examples include polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene hydrogenated castor oil derivative, mannitol hydroxy fatty acid ether, and the like.

Problems to be Solved by the Invention] Problems with the Prior Art However, nonionic surfactants containing low molecular weight oxyethylene chains have the advantage of having a wide HLB range and being able to be adjusted arbitrarily. Generally, they undergo oxidation over time and generate low-molecular-weight aldehydes and organic acids, causing odor and skin irritation, as well as causing a decrease in pH.

In addition, when polyhydric alcohol fatty acid ester type nonionic surfactants such as sorbitan fatty acid esters are used as components of external skin preparations that contain water and have a pH deviated from neutrality, the ester bonds may decompose. This tends to cause problems with stability over time and safety.

Furthermore, while hydroxy ethers of sugars such as sorbitol hydroxy aliphatic ethers have the advantage of good foaming, there is a problem that this foaming quality gives a poor impression when used as a solubilizer in lotions. .

Purpose of the Invention In view of the above circumstances, the present inventors have made extensive studies and found that maltitol aliphatic ether does not undergo oxidation over time and has a low We have completed the present invention by discovering that it does not generate molecular weight aldehydes or organic acids, cause odor or skin irritation, or cause a decrease in pH.

[Means for Solving the Problems] That is, the present invention has the general formula (■): I A--e-0-CH)n(I) 2 (wherein A represents n hydroxyl groups from maltitol). The removed residues R1 and R2 are a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, or a branched alkyl group, and n represents 1 or 2. be.

The maltitol used in the production of the maltitol aliphatic ether of the present invention may have any of the following structural formulas,
Examples of commercially available products include powdered Mavit (Kankosha), Mavit (Kankosha), maltitol (Matsumoto Trading Co., Ltd., Mokuzai Sangyo), and maltitol crystal (Kankosha).

In addition, the alkyl derivatives used in the production of the maltitol aliphatic ether of the present invention are as follows: It is a halogen salt of a trialkylammonium group such as ammonium bromide, or a hydroxyl group, and R1 and R2 are represented by a C1-C20 alkyl group or a branched alkyl group, and these may be used alone or in combination of one or more types. good.

In general formula (I), specific examples of 01-C20 alkyl groups and branched alkyl groups other than hydrogen atoms for R1 and R2 include methyl group, ethyl group, isopropyl group, pentyl group, hexyl group, heptyl group, etc. group, octyl group, lauryl group, myristyl group, palmityl group, stearyl group, 2-ethylhexyl group, isostearyl group, and the like.

In the maltitol aliphatic ether of the present invention represented by general formula (I), the residue A is maltitol, which is a hydrophilic group, and R
Since 1 and R2 are hydrophobic groups, it is preferable that the total number of carbon atoms in R1 and R2 is 10 to 20.

If the total number of carbon atoms in R1 and R2 is outside the range of 10 to 20, the balance between hydrophilicity and hydrophobicity will be lost, and the range of use as an activator will be narrowed, which is not preferable. Further, in general formula (I), n is preferably 1 or 2. n
When the number is 3 or more, the product becomes a wax and cannot be used as an activator.

The above-mentioned maltitol aliphatic ether is oily or solid, and has functions such as cleaning properties, dispersibility, emulsifying properties, moisturizing properties, and providing a rich feeling of use, as well as safety and
Due to its extremely high stability, it is widely used in pharmaceuticals, quasi-drugs,
It can be incorporated as an ingredient in cosmetics and cleaning products.

Next, a specific manufacturing method will be shown here.

The maltitol aliphatic ether of the present invention can be produced, for example, by the method of Robert et al. (Tetrahedron, IEL
, 2169-2172 (1979)).

That is, (II) is dimethylformamide, dimethylsulfoxide, dioxane, dimethylacetamide, N
-Dissolved in a non-aqueous solvent such as methylpyrrolidone, N-acetylmorpholine, N-methylsuccinimide, etc.
(% formula %): ) (In the formula, X is a halogen group such as fluorine, chlorine, bromine, or iodine, or a halogen salt of a trialkylammonium group such as trimethylammonium bromide, or a hydroxyl group, and R1 and R2 are It is obtained by adding an alkyl derivative represented by a C1-C20 alkyl group or a branched alkyl group, and stirring and reacting at 50-130°C in the presence of a catalyst. The above-mentioned catalysts include mineral acids such as sulfuric acid, alkalis such as lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium alcoholades such as sodium methylate and sodium ethylate, and amines such as N-methylbenzylamine. etc.

The molar ratio of (II) and (Ill) used in this reaction is preferably 1:1 to 3:1, and 2:1 to 3:1, for example when trying to obtain a monoether as the main product. 1
is even more preferable. If the molar ratio of (II) and (Ill) is out of this range, i.e., if the maltitol is too low, impurities such as triethers are likely to occur, and if it is too high, a large amount of maltitol will remain and hinder subsequent purification, so it is preferable. do not have.

When the compound represented by general formula (II [>) is completely consumed, acids such as acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, lithium hydroxide, sodium hydroxide
An alkali such as potassium hydroxide is added, and the reaction solvent is distilled off under reduced pressure.

The reaction product thus obtained has the general formula (I)
A maltitol aliphatic ether represented by , a salt during neutralization, maltitol, a maltitol aliphatic ether with three or more alkyl groups or branched alkyl groups, etc. coexist. Therefore, for example, when removing maltitol and salt, it is necessary to extract it with a solvent that does not dissolve maltitol such as methyl alcohol, ethyl alcohol, butyl alcohol, or isopropyl alcohol, or to partition it between water containing a large amount of salt and methyl ethyl ketone or n-butanol. It can be purified by separating the organic solvent layer. In addition, when removing maltitol and salt and maltitol aliphatic ether bonded with three or more alkyl groups or branched alkyl groups, the reaction product is suspended in water or a mixture of water and alcohol, and hyperporous polymer (for example, high porous resin manufactured by Mitsubishi Chemical Industries, Ltd.), water is first passed through a reverse phase distribution column such as octadecyl silica, and then a mixture of water and an alcohol such as methanol or ethanol or a polar organic solvent such as acetonitrile is used. It can be purified by passing a liquid through it and separating this liquid.

The maltitol aliphatic ether synthesized as described above is
It may be used after distilling off the extraction solvent or purifying with a column, or it may be used as it is.

[Effects of the Invention] The maltitol aliphatic ether of the present invention does not undergo oxidation over time, does not generate low molecular weight aldehydes or organic acids, does not cause odor or skin irritation, and does not have pH
will not cause a decrease in Moreover, even when used as a component of an external skin preparation whose pH is far from neutral, the ether bond is not decomposed, making it a surfactant with excellent safety and stability.

Furthermore, when the maltitol aliphatic ether of the present invention is used as a solubilizer in a lotion, it does not foam too well and has a good feel when used.

[Example] Hereinafter, the maltitol aliphatic ether of the present invention will be specifically explained with reference to Examples.

Note that the present invention is not limited to this. In addition, the test methods and evaluation methods employed in each example will also be explained here.

1st Ceremony” - Maltitol 1. Dissolve O,Og in 200ml of dimethyl sulfoxide that has been dried in advance, add 06g of sthorium hydroxide under stirring at 80°C, and stir for 30 minutes, then add 4.03g of myristyl bromide. The mixture was further heated and stirred at the above temperature for 4 hours. Then cool to room temperature,
Neutralized with IN hydrochloric acid. The reaction solvent was distilled off under reduced pressure,
The residue was fractionated using column chromatography using hyperporous polymer (high porous resin manufactured by Mitsubishi Kasei Corporation) using first purified water as a developing solvent and then ethyl alcohol:purified water = 1:1, resulting in a purified product. Salt, maltitol, and dimethyl sulfoxide were observed in the water eluate, and the eluate was concentrated in a ratio of ethyl alcohol: purified water (1:1), and then treated with N,O-(bistrimedelsilyl)acetamide, trimedelchlorosilane, and N. - After trimethylsilylation with an equal amount mixture of trimethylsilylimidazole, gas chromatography method (column packing material: Diasolid ZT manufactured by Nippon Chromato Industries Co., Ltd., inner diameter 3+n) was performed.
+n, length 50cm1 Heating rate: 100°C-340
°C, 10°C/min, carrier gas and flow rate: nitrogen, 50 m1/m12 in, detector: FID), a peak of maltitol monomyristyl ether was observed at a retention time of 12.57 minutes. Mm was done. The yield of maltitol monomyristyl ether was 4.1.1 g (yield 47.2%). The obtained maltitol monomyristyl ether was analyzed by methods (1) to (3).

(1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement device manufactured by JASCO Corporation, measurement was performed using the KBr tablet method.
Stretching vibration of hydroxyl group at 400 cm −', 2900 c
Methylene moiety of myristyl group 1300 ~ near m-'
Absorption due to ether bond at 1450 cm-', 858c
Absorption due to the α-glucoside bond of maltitol was observed at m-'. The results are shown in Figure 2.

(2) 13C-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using DMSO-ds as a solvent, the terminal methyl group of the myristyl group was found to be 14.0 ppm (■), the methylene moiety of the myristyl group was found to be 22 to 35 ppm (■ to ■), and the methylene moiety of the myristyl group to be 62 to 35 ppm (■ to ■). 10100pp～[phase])
Signals originating from the carbon in the maltitol moiety were observed. The results are shown in Figure 3.

(3) 'H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using DMSO-d6 as a solvent, the terminal methyl group of the myristyl group was found to be 0.86 ppm (Φ), the methylene moiety of the myristyl group was found to be 1.25 ppm (■), and 1.46 pp'm. (■) is the terminal ether bonding part of myristyl group, 3.0 to 5.0 ppm
Signals derived from hydrogen in the maltitol moiety were observed in ((1)-■), respectively. The results are shown in Figure 4.

One mouthful of 68.35 g of potassium iodide is 54.65 g of 95
% phosphoric acid aqueous solution, to which 11.55 g of 7
-Titradecene was added dropwise at room temperature. After the dropwise addition was completed, the reaction system was heated and stirred at 100°C for 5 hours. After cooling, 140 ml of diethyl ether and 200 ml of a 10% aqueous solution of sulfuric acid were added to the reaction system for extraction.

Furthermore, extraction was carried out three times with diethyl ether, and the diethyl ether layer was washed once with 200 ml of 10% aqueous sodium thiosulfate solution, twice with saturated brine, and once with purified water. Concentrate the diethyl ether layer to give 7-iodotetradecane 2
0.52g was obtained.

Next, 20.3 g of maltitol was dissolved in 100 ml of dimethyl sulfoxide that had been dried in advance, and 5.0 g of potassium hydroxide was dissolved at room temperature. After adding OOg and stirring for 30 minutes, 20.3 g of 7-iodotetradecane synthesized in advance by the above method was added dropwise over 1 hour. After the dropwise addition, the reaction system was raised to 60°C and stirred for 5 hours, and then further raised to 80°C and stirred for 3 hours. After the reaction, the reaction system was cooled to room temperature, poured into 500 ml of water, washed with hexane, and then poured into
Neutralized with hydrochloric acid. The reaction solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography using hyperporous polymer (high porous resin manufactured by Mitsubishi Chemical Industries, Ltd.) using first purified water and then ethyl alcohol:purified water as the developing solvent. When fractionating using =1=1, salt, maltitol, and dimethyl sulfoxide were found in the eluate of purified water, and the eluate of ethyl alcohol:purified water = 1:1 was concentrated.
This was trimedelsilylated with an isotropic mixture of N,O-(bistrimethylsilyl)acetamide, trimedelchlorosilane, and N-trimethylsilylimidazole, and then analyzed by gas chromatography under the same conditions as above, and the retention time was 14. , maltitol mono (1
-hexyl octyl) ether peak could be observed.

The yield of maltitol mono(1-hexyl octyl) ether was 10.7 g (yield 30.2%). The gas chromatogram is shown in FIG.

The obtained maltitol mono(1-hexyl octyl) ether was analyzed by methods (4) to (5).

(4) Infrared absorption spectrum measurement method: Measured using the KBr tablet method using an IRA-1 infrared absorption spectrum measurement device manufactured by JASCO Corporation.
stretching vibration of hydroxyl group at 3400 cm-', absorption due to ether bond at 1300 to 1450 cm-' of the methylene portion of myristyl group around 2900 cm-', and α- of multi)·-le at 858 m-'. Absorption due to glucoside bonds was observed. The results are shown in Figure 6.

(5) I3C-NMR measurement method JOEL FX-100 manufactured by JEOL Ltd.
When measured at room temperature using DMSO-d6 as a solvent, the two terminal methyl groups of the 1-hexyl octyl group were found to be 13.9 ppm (■), and 22 to 35 pm (■
~ ■) methylene moiety of myristyl group, 60-1010
Signals originating from the carbon of the maltitol moiety were observed at 4pp■ to O). The results are shown in FIG.

(6) 'H-NMR measurement method JOEL GX-100 manufactured by JEOL Ltd.
When measured at room temperature using DMSO-d6 as a solvent, 0.86 ppm (■) contains 6 hydrogen atoms of the terminal methyl group of the 1-hexyl octyl group, 1. ．． 24 pp
m (■) is the hydrogen of the methylene part of the 1-hexyl octyl group, 1.47 ppm (■) is the hydrogen of one hydrogen part of the ether bond of the 1-hexyl octyl group, 3.0 to 5.0 p
Signals derived from hydrogen in the maltitol moiety were observed at pm (Φ to ■), respectively. The results are shown in FIG.

In addition, the signal of 3.4-Op p rn is water (HDO
).

7 8 Safety/Stability Test (1) Hydrolysis Test 1% aqueous solutions of Examples 1 and 2 were heated at 90°C for 5 hours. A certain amount of the cooled aqueous solution was taken and extracted with ethyl ether, and the hydrolysis reaction was determined from the gas chromatogram of the extract.

(2) Aldehyde generation test Examples 1 and 2 were left in a container at 80° C. for 100 hours, and then 5 g of each sample was collected. After that, 500 water
ml and 3 ml of diluted phosphoric acid were added and distilled. When the distilled volume reached 190 ml, the distillation was stopped and water was added to make 200 ml, which was used as a test solution.

Take 10 ml of this test solution "e" and 5 ml of acetylacetone.
1 was added, shaken, and heated in a 60'C water bath for 10 minutes. After cooling, the absorbance at maximum absorption wavelengths around 420 nm and 420 nm was measured.

These results are shown in Table-1.

Table 1 As can be seen from Table 1, hydrolysis was hardly observed in any of the samples of Example 1.2.

On the other hand, in commercially available sucrose laurate and polyethylene glycol (PEG) laurate, about 20% and about 2% decomposition of ester groups was observed under the same conditions, respectively.

Further, in the case of sorbitol hydroxymyristyl ether synthesized in a laboratory, hydrolysis was hardly observed.

Further, the presence of aldehyde was not observed in any of the samples of Example 1.2.

On the other hand, when polyethylene glycol lauric acid ester 90 was similarly treated and evaluated, the presence of aldehyde was observed.

In addition, even when sucrose laurate ester and sorbitol hydroxymyristyl ether were treated in the same manner, the presence of aldehyde was not observed.

Effect Test The effect of applying the maltitol aliphatic ether of the present invention to the skin was evaluated in terms of skin irritation and feeling of use.

Samples (formulation examples 1 and 2) and controls (comparative examples 1 and 2) with the compositions shown below were administered to a panel of 25 men and women each, with the sample on one cheek and the control on the other cheek twice a day. After continuous application for one week, the irritation to the skin of the left and right cheeks and the feeling of use were evaluated. The criteria for each evaluation were as follows.

1 2 Skin irritation o: 0 to 5 out of 50 people felt a stinging or tight feeling on their skin.

◯: 6 to 20 out of 50 people felt a stinging or tight feeling on their skin.

△: 21 to 35 out of 50 people recognized a tingling or tight feeling on their skin.

X: 36 to 50 out of 50 people recognized a tingling or tight feeling on their skin.

Usability: 0: Usability is much better than the control ○: Usability is slightly better than the control △: Usability is the same as the control ×; Usability is better than the control As can be seen from Table 2, for the samples of the present invention, Skin irritation was low and good. On the other hand, polyoxyethylene (8
mol) sorbitan monooleate, polyoxyethylene (
The control using glycerin monostearate (8 mol) was highly irritating.

Furthermore, in the group formulated with sucrose lauric acid ester and sorbitol hydroxymyristyl ether, the majority of respondents said that it lathered too well and felt like shampoo and was unpleasant.

In addition, formulation examples 1 and 2 did not become cloudy and were stable even when left at 0°C, 125°C, and 150°C for one month, but the control and those using polyethylene glycol (PEG) laurate 3 4 When left at 50'C for one month, flocculation, cloudiness, and precipitation occurred.

Formulation example 1 (1) Glycerin (2) Propylene glycol (3) Oleyl alcohol (4) Maltitol monomyristyl ether obtained in Example 1 (3) Oleyl alcohol (4) Polyoxyethylene (8 mol) Sorbitan monooleate (5) Ethanol (6) Fragrance (7) Ethylparaben (8) Ion-exchanged water % by weight 3.0 4.0 0.1 1.5 0.1 1.5 10.0 Proper amount Proper amount Remaining formulation example 2 (1 ) Glycerin (2) Propylene glycol Weight % 3.0 4.0 (3) Oleyl alcohol (4) Maltitol monomyristyl ether obtained in Example 1 (3) Oleyl alcohol (4) Obtained in Example 2 Maltitol mono(1-hexyl octyl) ether (5) Ethanol (6) Fragrance (7) Ethyl paraben (8) Ion exchange water 0.1 1.5 0.1 1.5 10.0 Appropriate amount Appropriate amount Remaining comparative example 1 (1) Glycerin (2) Propylene glycol (3) Oleyl alcohol (4) Polyoxyethylene (8 mol) Sorbitan monoole I (5) Ethanol (6) Perfume weight % 3.0 4.0 0.1 1 .5 10.0 Appropriate amount 5 6 (7) Ethyl paraben (8) Ion exchange water Appropriate amount Remaining comparative example 2 (1) Glycerin (2) Propylene glycol (3) Oleyl alcohol (4) Polyoxyethylene (8 mol) Glycerin mono Stearate (5) Ethanol 10.0 (
6) Perfume, appropriate amount (7) Ethylparaben, appropriate amount (8) Ion-exchanged water, remaining weight % 3.0 4.0 0.1 1.5.

In addition, Fig. 5, Fig. 6, Fig. 7, and Fig. 8 are gas chromatogram, infrared absorption spectrum chart, and 13C-NMR of maltitol mono(1-hexyl ocdyl) ether obtained in Example 2, respectively. These are a spectrum chart and an 1 H-N MR spectrum chart.

Claims (1)

[Claims] A maltitol aliphatic ether represented by the general formula (I). ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (However, in the formula, A is the residue obtained by removing n hydroxyl groups from maltitol, R^1 and R^2 are hydrogen atoms, and have 1 to 2 carbon atoms.
0 alkyl group or branched alkyl group, and n represents 1 or 2. )