HYDROGEL-FORMING MATERIAL, PREMIX, AND HYDROGEL FORMATION METHOD

Abstract

A hydrogel-forming material, a premix, and a method for forming a hydrogel through a simple process at room temperature. The material including: a disperse phase (A) including a lipid peptide-based gelator including at least one of a compound of Formula (1) or pharmaceutically usable salt thereof, water, and a fatty acid salt; and a phase (B) that includes a water-soluble acidic polymer:

##STR00001##

(where R1 is a C9-23 aliphatic group, R2 is a hydrogen atom or a C1-4 alkyl group that optionally has a C1-2 branched chain, R3 is a (CH2)n-X group, n is a number of 1 to 4, X is an amino group, a guanidino group, a CONH2 group, a 5-membered ring optionally containing 1 to 3 nitrogen atom(s), a 6-membered ring optionally containing 1 to 3 nitrogen atom(s), or a condensed heterocycle that contains a 5-membered ring and a 6-membered ring optionally containing 1 to 3 nitrogen atom(s)).

Claims

1. A premix for preparation of a hydrogel for use in a cosmetic or a quasi drug, the premix comprising: a lipid peptide-based gelator consisting of at least one of a compound of Formula (1) or a pharmaceutically usable salt thereof; water; and a fatty acid salt: ##STR00004## (where R.sup.1 is a C.sub.9-23 aliphatic group, R.sup.2 is a hydrogen atom or a C.sub.1-4 alkyl group that optionally has a C.sub.1-2 branched chain, R.sup.3 is a (CH.sub.2).sub.nX group, n is a number of 1 to 4, X is an amino group, a guanidino group, a CONH.sub.2 group, a 5-membered ring optionally containing 1 to 3 nitrogen atom(s), a 6-membered ring optionally containing 1 to 3 nitrogen atom(s), or a condensed heterocycle that contains a 5-membered ring and a 6-membered ring optionally containing 1 to 3 nitrogen atom(s)).

Description

EXAMPLES

[0118] The present invention will be described in more detail by examples and test examples. The scope of the present invention, however, is not limited to these examples.

Synthesis Example 1: Synthesis of Lipid Peptide (N-Palmitoyl-Gly-His)

[0119] A lipid peptide used in this example as a gelator was synthesized by a method below.

[0120] 14.2 g (91.6 mmol) of histidine, 30.0 g (91.6 mmol) of N-palmitoyl-Gly-methyl, and 300 g of toluene were added to a 500-mL four-necked flask, to which 35.3 g (183.2 mmol) of a 28% methanol solution of sodium methoxide as a base was added, and the resulting solution was heated in an oil bath to 60 C. and was stirred for 1 hour. Subsequently, the resulting solution that was removed from the oil bath was left to cool to reach 25 C., was reprecipitated with 600 g of acetone, and was filtered. The resulting solid was dissolved in a mixed solution of 600 g of water and 750 g of methanol, to which 30.5 ml (183.2 mmol) of 6-N hydrochloric acid was added for neutralization to precipitate a solid, which was filtered. The resulting solid was then dissolved in a mixed solution of 120 g of tetrahydrofuran and 30 g of water at 60 C., to which 150 g of ethyl acetate was added, and the resulting solution was cooled from 60 C. to 30 C. Subsequently, the precipitated solid was filtrated. The resulting solid was dissolved in a solvent of 120 g of tetrahydrofuran and 60 g of acetonitrile and then heated to 60 C. The resulting solution was stirred for 1 hour and then cooled, followed by filtration. The resulting solid was washed with 120 g of water and filtrated, followed by drying under reduced pressure to obtain 26.9 g (yield: 65%) of a white crystal of a free form of N-palmitoyl-Gly-His (hereinafter, also simply called N-palmitoyl-Gly-His).

Example 1 to Example 14 and Comparative Example 1 to Comparative Example 3: Preparation of Disperse Phase (A) (Premix) Including N-Palmitoyl-Gly-His and Evaluation of Dispersibility Thereof

[0121] The N-palmitoyl-Gly-His (called Pal-GH in tables) prepared in the synthesis example, sodium palmitate (manufactured by Tokyo Chemical Industry Co., Ltd.) as an additive, and water were placed in a 300-mL beaker at a proportion shown in the following tables, followed by heating to the liquid temperature of 80 C. for 20 minutes to 90 minutes with stirring at 300 rpm. After the heating was terminated, the resulting solution was left to cool for 1 hour with stirring at 300 rpm. The amount of water lost by evaporation was added, followed by stirring at 300 rpm for another 1 minute. The resulting solution was left at room temperature overnight or longer to prepare a disperse phase (A). A LABORATORY HIGH POWER MIXER manufactured by As One Corporation was used as a mixer for stirring.

[0122] Dispersibility in preparation of the disperse phase (A) was evaluated by visual observation as, when the N-palmitoyl-Gly-His and the additive were dispersed in water during the heating process and neither separation of water nor deposition of solid matter from the resulting disperse phase (A) occurred, or as x when the N-palmitoyl-Gly-His and/or the additive did not disperse in water during the heating process and solid matter could be observed. The pH of the disperse phase (A) was measured with a twin pH meter (manufactured by As One Corporation).

[0123] The results are shown in Table 1 to Table 4.

TABLE-US-00001 TABLE 1 Comparative Composition Examples Example (% by mass) 1 2 3 4 1 Pal-GH 1.0 1.0 1.0 1.0 1.0 Sodium 0.30 0.61 1.23 1.85 palmitate*.sup.1 Water Rest Rest Rest Rest Rest Total 100 100 100 100 100 Test results are as follows Dispersibility X in disperse phase (A) pH 10.3 10.3 9.7 10.3 *.sup.1manufactured by Tokyo Chemical Industry Co., Ltd.

TABLE-US-00002 TABLE 2 Composition Examples (% by mass) 5 6 7 8 9 Pal-GH 0.8 0.8 0.8 0.6 0.6 Sodium 0.25 0.49 1.48 0.18 0.37 palmitate*.sup.1 Water Rest Rest Rest Rest Rest Total 100 100 100 100 100 Test results are as follows Dispersibility in disperse phase (A) pH 10.3 10.3 10.2 10.4 10.4 *.sup.1manufactured by Tokyo Chemical industry Co., Ltd.

TABLE-US-00003 Table 3 Composition Examples (% by mass) 10 11 12 13 14 Pal-GH 0.6 0.5 0.5 0.4 0.4 Sodium 1.11 0.15 0.30 0.24 0.2 palmitate*.sup.1 Water Rest Rest Rest Rest Rest Total 100 100 100 100 100 Test results are as follows Dispersibility in disperse phase (A) pH 10.3 10.3 10.4 10.4 10.3 *.sup.1manufactured by Tokyo Chemical Industry Co., Ltd.

TABLE-US-00004 TABLE 4 Composition Comparative Examples (% by mass) 2 3 Pal-GH 0.4 Sodium 0.2 palmitate*.sup.1 Water Rest Rest Total 100 100 Test results are as follows Dispersibility x x in disperse Phase (A) pH 7.8 10.5 *.sup.1manufactured by Tokyo Chemical Industry Co., Ltd.

Example 15 to Example 52 and Comparative Example 4 and Comparative Example 5: Test for Neutralization and Gelation of Disperse Phase (A) (Premix) Including N-Palmitoyl-Gly-His

[0124] The disperse phase (A) including the N-palmitoyl-Gly-His obtained in Example 1 to Example 14 was placed in a 200-mL beaker at a proportion shown in the following tables, and, while stirring at 300 rpm, a disperse phase (B) (a polyacrylic acid (PAA) dispersion or a carbomer dispersion) shown below was added thereto, followed by stirring at 300 rpm for 1 minute to prepare a hydrogel-forming material. A LABORATORY HIGH POWER MIXER manufactured by As One Corporation was used for stirring. The resulting mixture was left at room temperature for 1 hour and then a portion thereof was placed in a Mighty Vial (No. 3, manufactured by Maruemu Corporation).

[0125] Hydrogelation ability was evaluated as gelled () when inversion of the vial did not make the solution flow down because the solution had lost its fluidity or as not gelled (x) when the solution flowed down. Occurrence of syneresis in gel was also observed. In the case where the mixture was gelled, the pH of the gel was measured with a twin pH meter (manufactured by As One Corporation), while in the case where the mixture was not gelled, the pH of the liquid was measured in the same manner. Final compositions after the hydrogelation test and the test results are shown in the following tables. In the tables, the symbol - refers to the case where no test was performed.

TABLE-US-00005 TABLE 5 Composition Examples (% by mass) 15 16 17 18 Disperse Example 1 50 phase Example 2 50 Example 3 50 Example 4 50 0.4% PAA*.sup.2 dispersion 50 50 50 50 Water Total 100 100 100 100 Pal-GH 0.5 0.5 0.5 0.5 Sodium palmitate 0.15 0.305 0.615 0.925 PAA*.sup.2 0.2 0.2 0.2 0.2 Water Rest Rest Rest Rest Total 100 100 100 100 Test Results Evaluation of hydrogelation ability pH 5.3 6.2 7.5 8.5 *.sup.2polyacrylic acid (molecular weight: 1,000,000) manufactured by Wako Pure Chemical Industries, Ltd.

TABLE-US-00006 TABLE 6 Composition (% by Examples mass) 19 20 21 22 23 Disperse Example 2 50 50 50 phase Example 3 50 50 1.0% PAA*.sup.2 50 dispersion 0.4% PAA*.sup.2 50 dispersion 0.2% PAA*.sup.2 50 dispersion 0.4% PAA*.sup.3 50 dispersion 0.4% PAA*.sup.4 50 dispersion Water Total 100 100 100 100 100 Pal-GH 0.5 0.5 0.5 0.5 0.5 Sodium palmitate 0.305 0.615 0.615 0.305 0.305 PAA*.sup.2 0.1 0.5 0.2 PAA*.sup.3 0.2 PAA*.sup.4 0.2 Water Rest Rest Rest Rest Rest Total 100 100 100 100 100 Test Results Evaluation of X X hydrogelation ability pH 8.8 5.3 7.1 6.0 6.1 *.sup.2polyacrylic acid (molecular weight: 1,000,000) manufactured by Wako Pure Chemical Industries, Ltd. *.sup.3polyacrylic acid (molecular weight: 25,000) manufactured by Wako Pure Chemical Industries, Ltd. *.sup.4polyacrylic acid (molecular weight: 5,000) manufactured by Wako Pure Chemical Industries, Ltd.

TABLE-US-00007 TABLE 7 Composition Examples (% by mass) 24 25 26 27 Disperse Example 2 25 phase Example 5 50 Example 6 50 Example 7 50 0.4% PAA*.sup.2 dispersion 50 0.32% PAA*.sup.2 dispersion 50 50 0.2% PAA*.sup.2 dispersion 50 Water 25 25 Total 100 100 100 100 Pal-GH 0.25 0.4 0.4 0.4 Sodium palmitate 0.152 0.109 0.245 0.741 PAA*.sup.2 0.1 0.16 0.2 0.16 Water Rest Rest Rest Rest Total 100 100 100 100 Test Results Evaluation of x x hydrogelation ability pH 6.6 5.3 6.2 9.1 *.sup.2polyacrylic acid (molecular weight: 1,000,000) manufactured by Wako Pure Chemical Industries. Ltd.

TABLE-US-00008 TABLE 8 Composition (% by Examples mass) 28 29 30 31 32 Disperse Example 6 25 12.5 phase Example 8 50 Example 9 50 Example 10 50 0.24% PAA*.sup.2 dispersion 50 50 50 0.16% PAA*.sup.2 dispersion 50 0.08% PAA*.sup.2 dispersion 50 Water 25 37.5 Total 100 100 100 100 100 Pal-GH 0.2 0.1 0.3 0.3 0.3 Sodium palmitate 0.123 0.061 0.09 0.185 0.555 PAA*.sup.2 0.08 0.04 0.12 0.12 0.12 Water Rest Rest Rest Rest Rest Total 100 100 100 100 100 Test Results Evaluation of X X X X hydrogelation ability pH 6.4 6.8 5.5 6.4 5.3 *.sup.2polyacrylic acid (molecular weight: 1,000,000) manufactured by Wako Pure Chemical Industries, Ltd.

TABLE-US-00009 TABLE 9 Composition Examples (% by mass) 31 34 35 Disperse Example 50 50 50 phase 2 0.2% carbomer*.sup.5 50 dispersion 0.1% carbomer*.sup.5 50 dispersion 0.05% carbomer*.sup.5 50 dispersion Water Total 100 100 100 Pal-GH 0.5 0.5 0.5 Sodium palmitate 0.305 0.305 0.305 Carbomer*.sup.5 0.1 0.05 0.025 Water Rest Rest Rest Total 100 100 100 Test Results Evaluation of x x hydrogelation ability pH 7.5 9.5 9.8 *.sup.5Carbopol 940 manufactured by ITO Inc.

TABLE-US-00010 TABLE 10 Composition Examples (% by mass) 36 37 38 39 Disperse Example 11 50 phase Example 12 50 50 50 0.2% carbomer*.sup.5 50 50 dispersion 0.1% carbomer*.sup.5 50 dispersion 0.05% carbomer*.sup.5 50 dispersion Water Total 100 100 100 100 Pal-GH 0.25 0.25 0.25 0.25 Sodium palmitate 0.075 0.15 0.15 0.15 Carbomer*.sup.5 0.1 0.1 0.05 0.025 Water Rest Rest Rest Rest Total 100 100 100 100 Test Results Evaluation of x x hydrogelation ability pH 6.9 6.8 8.2 9.6 *.sup.5Carbopol 940 manufactured by ITO Inc.

TABLE-US-00011 TABLE 11 Composition Examples (% by mass) 40 41 42 43 Disperse Example 13 50 50 phase Example 14 50 50 0.2% carbomer*.sup.5 50 50 dispersion 0.1% carbomer*.sup.5 50 50 dispersion Water Total 100 100 100 100 Pal-GH 0.2 0.2 0.2 0.2 Sodium palmitate 0.12 0.12 0.1 0.1 Carbomer*.sup.5 0.1 0.05 0.1 0.05 Water Rest Rest Rest Rest Total 100 100 100 100 Test Results Evaluation of x x hydrogelation ability pH 6.2 7.6 5.7 5.8 *.sup.5Carbopol 940 manufactured by ITO inc.

TABLE-US-00012 TABLE 12 Composition (% by Examples mass) 44 45 46 47 48 Disperse Example 25 25 phase 14 Example 2 50 50 50 0.2% carbomer*.sup.5 50 dispersion 0.1% carbomer*.sup.5 50 dispersion 0.2% carbomer*.sup.6 50 dispersion 0.1% carbomer*.sup.6 50 dispersion 0.05% carbomer*.sup.6 50 dispersion Water 25 25 Total 100 100 100 100 Pal-GH 0.1 0.1 0.5 0.5 0.5 Sodium palmitate 0.05 0.05 0.305 0.305 0.305 Carbomer*.sup.5 0.1 0.05 Carbomer*.sup.6 0.1 0.05 0.025 Water Rest Rest Rest Rest Rest Total 100 100 100 100 100 Test Results Evaluation of X X X X hvdrogelation ability pH 6.3 6.6 7.9 9.3 10 *.sup.5Carbopol 940 manufactured by ITO Inc. *.sup.6Hiviswako 105 manufactured by Wako Pure Chemical Industries, Ltd.

TABLE-US-00013 TABLE 13 Composition Examples (% by mass) 49 50 51 52 Disperse Example 12 50 50 50 phase Example 14 50 0.2% carbomer*.sup.6 50 50 dispersion 0.1% carbomer*.sup.6 50 dispersion 0.05% carbomer*.sup.6 50 dispersion Water Total 100 100 100 100 Pal-GH 0.25 0.25 0.25 0.2 Sodium palmitate 0.15 0.15 0.15 0.1 Carbomer*5 0.1 0.05 0.025 0.1 Water Rest Rest Rest Rest Total 100 100 100 100 Test Results Evaluation of x x hydrogelation ability pH 6.4 8.0 9.5 6.0 *.sup.6Hiviswako 105 manufactured by Wako Pure Chemical Industries, Ltd.

TABLE-US-00014 TABLE 14 Composition Comparative Examples (% by mass) 4 5 Disperse Comparative 50 phase Example 2 Comparative 50 Example 3 0.2% carbomer*.sup.5 50 50 dispersion Water Total 100 100 Pal-GH 0.2 Sodium palmitate 0.1 Carbomer*5 0.1 0.1 Water Rest Rest Total 100 100 Test Results Evaluation of x x hydrogelation ability pH 3.7 5.9 *.sup.5Carbopol 940 manufactured by ITO Inc.

Example 53: Gel Spray Test on N-Palmitoyl-Gly-His Hydrogel

[0126] The hydrogel-forming material prepared in the examples was placed in a spray vial (Maruemu Corporation, 3L), followed by spraying two consecutive times toward the center of a glass plate (10 cm7.5 cm) that was placed 5 cm away from the tip of the nozzle of the spray vial. Observation was performed until the dripping stopped, followed by measurement of the longer diameter and the shorter diameter of the sprayed mark on the glass and the length of the dripping. The results of the spray test are shown in the following tables. In the tables, the symbol - refers to the case where no test was performed.

TABLE-US-00015 TABLE 15 Hydrogel-forming material Nos. (Example Nos.) Test Results 15 16 17 18 19 20 21 22 Spray length (mm) 14 13 0 13 30 10 0 Spray width (mm) 12 17 0 20 32 7 0 Dripping (mm) 0 0 0 0 0 0 0

TABLE-US-00016 TABLE 16 Hydrogel-forming material Nos. (Example Nos.) Test Results 23 24 25 26 27 28 29 30 31 Spray length (mm) 25 25 10 26 40 34 24 22 Spray width (mm) 30 20 14 24 32 35 31 30 Dripping (mm) 0 0 0 >20 0 0 10 0

TABLE-US-00017 TABLE 17 Hydrogel-forming material Nos. (Example Nos.) Test Results 32 33 34 35 36 37 38 Spray length (mm) 28 0 20 10 27 12 35 Spray width (mm) 30 0 25 7 30 11 30 Dripping (mm) >20 0 0 0 0 0 0

TABLE-US-00018 TABLE 18 Hydrogel-forming material Nos. (Example Nos.) Test Results 39 40 41 42 43 44 45 Spray length (mm) 20 20 50 37 40 28 30 Spray width (mm) 23 23 50 39 35 27 32 Dripping (mm) >15 0 0 0 0 0 3

TABLE-US-00019 TABLE 19 Hydrogel-forming material Nos. (Example Nos.) Test Results 46 47 48 49 50 51 52 Spray length (mm) 21 25 24 14 41 38 28 Spray width (mm) 21 23 25 19 35 34 21 Dripping (mm) 0 0 >15 0 0 5 0

Example 54: Test to Evaluate Re-Forming Ability of N-Palmitoyl-Gly-His Hydrogel

[0127] In a Mighty Vial (No. 3, manufactured by Maruemu Corporation), 4 g of the hydrogel-forming material prepared in the examples was placed, followed by stirring with a vortex mixer (Scientific Industries, Inc.) for 1 minute. Then, the vial was left still standing at room temperature overnight or longer. Evaluation was conducted as not converted into a sol () when no solation was confirmed after mixing with the vortex mixer, as re-formed () when the solution lost its fluidity after being converted into a sol and left still standing, and inversion of the vial did not make the solution flow down, or as not re-formed (x) when the solution flowed down. The symbol - refers to the case where no test was performed.

TABLE-US-00020 TABLE 20 Hydrogel-forming material Nos. (Example Nos.) Test Result 15 16 17 18 19 20 21 22 Hydrogel re-forming X ability

TABLE-US-00021 TABLE 21 Hydrogel-forming material Nos. (Example Nos.) Test Result 23 24 25 26 27 28 29 30 31 Hydrogel re-forming X ability

TABLE-US-00022 TABLE 22 Hydrogel-forming material Nos. (Example Nos.) Test Result 32 33 34 35 36 37 38 Hydrogel re-forming ability

TABLE-US-00023 TABLE 23 Hydrogel-forming material Nos. (Example Nos.) Test Result 39 40 41 42 43 44 45 Hydrogel re-forming ability

TABLE-US-00024 TABLE 24 Hydrogel-forming material Nos. (Example Nos.) Test Result 46 47 48 49 50 51 52 Hydrogel re-forming ability

Example 55 to Example 73: Test for Neutralization and Gelation of N-Palmitoyl-Gly-His

<Preparation of Phase A (Disperse Phase Including Pal-GH)>

[0128] The N-palmitoyl-Gly-His prepared in the synthesis example, a fatty acid, a 1-N aqueous sodium hydroxide solution, purified water, and other additives were placed in a 300-mL beaker at a proportion shown in the following tables, followed by heating to a the liquid temperature of 80 C. for 30 minutes with stirring at 300 rpm. The Rest in the row Purified water refers to the value obtained by subtracting the amount of the components in the phase A and the phase B other than purified water from the sum (100% by mass) of the components in the phase A and the phase B. Then, heating was terminated and the resulting mixture was left to cool for 1 hour with stirring at 300 rpm. The amount of water lost by evaporation was added, followed by stirring at 300 rpm for another 1 minute. The resulting mixture was left at room temperature overnight or longer to prepare a disperse phase including PalGH to serve as a phase A. In Comparative Example 6 to Comparative Example 9, the phases A did not include Pal-GH.

[0129] In these examples, A LABORATORY HIGH POWER MIXER manufactured by As One Corporation was used for stirring.

<Preparation of Phase B (Disperse Phase Including Water-Soluble Acidic Polymer)>

[0130] A water-soluble acidic polymer (a carboxyvinyl polymer, an acrylic acid-alkyl methacrylate copolymer), purified water, and other additives were placed in a 200-mL beaker at a proportion shown in the following tables, followed by stirring at 300 rpm at room temperature (about 25 C.) to adequately disperse the components to prepare a disperse phase including a water-soluble acidic polymer to serve as a phase B. In Comparative Example 10 and Comparative Example 11, citric acid or lactic acid was used instead of the acidic polymer.

<Preparation of Hydrogel-Forming Material and Hydrogel>

[0131] The phase B (disperse phase including a water-soluble acidic polymer) was added to the phase A (disperse phase including PalGH) obtained as described above at room temperature (about 25 C.) with stirring at 300 rpm, followed by stirring for about 10 minutes to prepare a hydrogel-forming material. A portion of the resulting mixture was placed in a Mighty Vial (No. 3, manufactured by Maruemu Corporation), which was then left still standing at room temperature for 1 hour. Hydrogelation ability was evaluated as hard gel formed () when inversion of the vial did not make the solution flow down because the solution had lost its fluidity and the gel formed was hard enough not to disintegrate due to vibration applied thereto, as gelled () when the gel formed became fluid due to vibration applied thereto, or as not gelled (x) when the resulting solution flowed down. A twin pH meter (manufactured by As One Corporation) was used to measure the pH of the gel in the case where the mixture was gelled or the pH of the sol in the case where the mixture was not gelled. Final compositions after the hydrogelation test and the test results are shown in the following tables.

TABLE-US-00025 TABLE 25 Composition Examples (% by mass) 55 56 57 58 A Pal-GH 0.5 0.5 0.2 0.2 palmitic 0.25 0.25 0.1 0.1 acid*.sup.7 1 mol/L 1.02 1.02 0.41 0.41 aqueous sodium hydroxide solution*.sup.8 purified Rest Rest Rest Rest water B carboxyvinyl 0.2 0.1 0.2 0.1 polymer*.sup.9 purified 49.8 49.9 49.8 49.9 water Total 100 100 100 100 Evaluation of hydrogelation ability pH 6.5 8.5 5.3 6.5 *.sup.7manuflictured by Kao Corporation. Lunac P-95 *.sup.8manufactured by Junsei Chemical Co., Ltd. *.sup.9manufactured by ITO Inc. Carbopol 940

TABLE-US-00026 TABLE 26 Composition Comparative Examples (% by mass) 6 7 8 9 A Pal-GH 0 0 0 0 palmitic 0.25 0.25 0.1 0.1 acid*.sup.7 1 mol/L 1.02 1.02 0.41 0.41 aqueous sodium hydroxide solution*.sup.8 purified Rest Rest Rest Rest water B carboxyvinyl 0.2 0.1 0.2 0.1 polymer*.sup.9 purified 49.8 49.9 49.8 49.9 water Total 100 100 100 100 Evaluation of x x x x hydrogelation ability pH 6.8 8.2 5.5 6.5 *.sup.7manufactured by Kao Corporation, Lunac P-95 *.sup.8manufactured by Junsei Chemical Co., Ltd. *.sup.9manufactured by ITO Inc. Carbopol 940

TABLE-US-00027 Table 27 Composition Examples (% by mass) 59 60 61 62 A Pal-GH 0.5 0.5 0.2 0.2 stearic 0.25 0.25 0.1 0.1 acid*.sup.10 oleic acid*.sup.11 1 mol/L 0.92 0.92 0.37 0.37 aqueous sodium hydroxide solution*.sup.8 purified Rest Rest Rest Rest water B carboxyvinyl 0.2 0.1 0.2 0.1 polymer*.sup.9 purified 49.8 49.9 49.8 49.9 water Total 100 100 100 100 Evaluation of hydrogelation ability pH 6.5 8.2 5.3 6.3 *.sup.8manufactured by Junsei Chemical Co., Ltd. *.sup.9manufactured by ITO Inc. Carbopol 940 *.sup.10manufactured by Kao Corporation. Lunac S-98 *.sup.11manufactured by Kao Corporation. Lunac O-LL-V

TABLE-US-00028 TABLE 28 Composition Examples (% by mass 63 64 65 66 A Pal-GH 0.5 0.5 0.2 0.2 stearic acid*.sup.10 oleic acid*.sup.11 0.25 0.25 0.1 0.1 1 mol/L 0.92 0.92 0.37 0.37 aqueous sodium hydroxide solution*.sup.8 purified Rest Rest Rest Rest water B carboxyvinyl 0.1 0.1 0.1 0.1 polymer*.sup.9 purified 49.8 49.9 49.8 49.9 water Total 100 100 100 100 Evaluation of hydrogelation ability pH 6.5 7.8 5.6 5.7 *.sup.8manufactured by Junsei Chemical Co., Ltd. *.sup.9manufactured by ITO Inc. Carbopol 940 *.sup.10manufactured by Kao Corporation, Lunac S 98 *.sup.11manufactured by Kao Corporation. Lunac O-LL-V

TABLE-US-00029 TABLE 29 Composition (% by Examples mass) 67 68 69 70 71 A Pal-GH 0.5 0.5 0.5 0.5 0.5 palmitic 0.25 0.25 0.25 0.25 0.25 acid*.sup.7 1 mol/L 1.02 1.02 1.02 1.02 1.02 aqueous sodium hydroxide solution*.sup.8 1,3-butylene 10 glycol*.sup.12 glycerin*.sup.13 10 purified Rest Rest Rest Rest Rest water B carboxyvinyl 0.2 0.2 0.2 0.2 0.2 polymer*.sup.9 1,3-butylene 10 glycol*.sup.12 Glycerin*.sup.13 10 purified 49.8 49.8 49.8 39.8 39.8 water Total 100 100 100 100 100 Evaluation of hydrogelation ability pH 6.5 6.6 6.7 6.8 6.7 *.sup.7manufactured by Kao Corporation. Lunac P-95 *.sup.8manufactured by Junsei Chemical Co., Ltd. *.sup.9manufactured by ITO Inc. Carbopol 940 *.sup.12manufactured by ITO Inc. *.sup.13manufactured by ITO Inc.

TABLE-US-00030 TABLE 30 Composition Examples Comparative Examples (% by mass 72 73 10 11 A Pal-GH 0.5 0.5 0.5 0.5 palmitic acid*.sup.7 0.25 0.25 0.25 0.25 1 mol/L 1.02 1.02 1.02 1.02 aqueous sodium hydroxide solution*.sup.8 purified Rest Rest Rest Rest water B carboxyvinyl 0.2 polymer*.sub.9 acrylic 0.2 acid-alkyl methacrylate copolymer*.sup.14 citric acid*.sup.15 0.2 lactic acid*.sup.16 0.2 purified 49.8 49.8 49.8 49.8 water Total 100 100 100 100 Evaluation of X X hydrogelation ability pH 6.5 6.5 4.2 4.3 *.sup.7manufactured by Kao Corporation. Lunac P-95 *.sup.8manufactured by Junsei Chemical Co., Ltd. *.sup.9manufactured by ITO Inc. Carbopol 940 *.sup.14manufactured by Nikko Chemicals Co., Ltd. PEMULEN TR-1 *.sup.15manufactured by Wako Pure Chemical Industries, Ltd. *.sup.16manufactured by Wako Pure Chemical Industries, Ltd.