JPH08310925A - Clathrated preservative for shampoo - Google Patents

Abstract

PURPOSE: To provide a clathrated shampoo preservative of high quality which can prevent skins and mucous membranes from being irritated by undesirable stimulation with the preservative, when a shampoo is used. CONSTITUTION: Benzoic acid, salicylic acid, sodium benzoate or sodium salicylate as a preservative is clathrated in α, β or γ-cyclodextrin to form cyclodextrin/ benzoic acid clathrate (1), cyclodextrin/salicylic acid clathrate (2), cyclodextrin/ sodium benzoate clathrate (3) and cyclodextrin/sodium salicylate clathrate (4). One of these clathrates is added to shampoo as a preservative in an amount of 0.05-1.0wt.%.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to preservatives for shampoos, and more particularly to preservatives such as benzoic acid and salicylic acid, which have been conventionally blended directly with shampoos, into α-, β-, or γ-cyclodextrin. The present invention relates to an inclusion preparation of a preservative formed by inclusion.

[0002]

BACKGROUND OF THE INVENTION Shampoo is used to wash and clean dirt on the scalp and hair to keep the scalp and hair beautiful.

Benzoic acid, salicylic acid and their sodium salts are widely used as preservatives for shampoos, but these preservatives are irritating to skin and mucous membranes and are not suitable for use by hypersensitive persons. Inferior in safety.

[0004]

[Problems to be Solved by the Invention] Unnecessary irritation to the skin and mucous membranes caused by preservatives associated with the use of shampoo is prevented, and the quality is milder and safer to the skin and mucous membranes. There is a strong demand for preservative formulations for shampoos.

[0005]

[Means and Actions for Solving Problems] The present inventors maintain the antiseptic activity of benzoic acid and salicylic acid,
As a result of studying to develop a highly safe antiseptic for shampoo that does not irritate the skin and mucous membranes, by utilizing the inclusion function of the cyclodextrin molecule, it was found that the intended purpose can be achieved, the present invention. It came to completion.

Both benzoic acid and salicylic acid have low solubility in an aqueous solution. However, inclusion of these in cyclodextrin improves the dispersibility in an aqueous solution, and thus the penetration of antiseptic activity is improved. The bactericidal action of each clathrate can sufficiently achieve the purpose of antiseptic sterilization of shampoos.

Benzoic acid, salicylic acid or their sodium salts, which are irritating to skin and mucous membranes, are included in cyclodextrin molecules to form cyclodextrin / benzoic acid inclusion preparation (1), cyclodextrin / salicylic acid inclusion preparation, respectively. By forming the contact preparation (2), the cyclodextrin / sodium benzoate inclusion preparation (3) or the cyclodextrin / sodium salicylate inclusion preparation (4), the irritation to the skin and mucous membranes is reduced, and thus these preservatives are added. It can be used safely by sensitive people.

The case of inclusion of a preservative in cyclodextrin has been reported so far only in the case of alkylparaben, and no studies have been conducted on inclusion of benzoic acid, salicylic acid and sodium salts thereof. , And there is no example of blending them in shampoo.

The clathrate used in the present invention, α-,
It is one kind selected from β- or γ-cyclodextrin, and benzoic acid or salicylic acid or a sodium salt thereof is included.

1 mol of each of α-cyclodextrin and β-cyclodextrin includes 1 mol of each of benzoic acid and salicylic acid (referred to as guest compound), and 2 mol of γ-cyclodextrin includes 1 mol of each guest compound.

To prepare an inclusion preparation, α- or β-
A cyclodextrin / guest compound inclusion solution was prepared by dissolving them in equimolar amounts, stirred at room temperature for 4 to 24 hours, and then cooled to form a precipitate of the cyclodextrin / guest compound inclusion preparation by filtration or centrifugation. It is separated and then dried naturally or under reduced pressure. γ
-Cyclodextrin contains 1 guest compound each in 2 moles
An inclusion preparation is similarly prepared using moles.

The inclusion preparation of cyclodextrin / preservative thus prepared has a shampoo of 0.05 to 1.0% by weight, preferably 0.1 to 0.6% by weight as a preservative. Is blended with. By using this method, irritation to the skin and mucous membranes due to direct incorporation of the preservative is suppressed, and a shampoo having excellent safety can be manufactured. The use of this cyclodextrin inclusion preparation is
It has no effect on the composition of the shampoo.

The inclusion preparation of cyclodextrin / preservative in the present invention can be incorporated as a highly safe preservative in cosmetics other than shampoo.

Next, the present invention will be specifically described with reference to examples.

[0015]

Example 1 A precipitate formed by dissolving 48.6 g (50 mmol) of α-cyclodextrin and 6.1 g (50 mmol) of benzoic acid in 400 ml of water, stirring the mixture at room temperature for 24 hours and then cooling. Are centrifuged and then dried under reduced pressure. In addition, 9.1 g (8 mmol) of β-cyclodextrin and 1.0 g (8 mmol) of benzoic acid were dissolved in 500 ml of water, stirred at room temperature for 24 hours, cooled, and the resulting precipitate was centrifuged. Dry under reduced pressure. As described above, 32.0 g of the α-cyclodextrin / benzoic acid inclusion preparation (a) or 6.0 g of the β-cyclodextrin / benzoic acid inclusion preparation (b) are obtained.

In order to confirm that these clathrate preparations (a) and (b) have the same antiseptic and bactericidal effect as the case of using benzoic acid alone, the growth inhibition in bacterial culture was evaluated. Escherichia coli (Escherichia coli) was added to a nutrient liquid medium containing both inclusion preparations (a) and (b) at 1.79% by weight and 2.06% by weight (corresponding to 0.2% by weight as a pure content of benzoic acid). ) And Bacillus subtilis (Bacil
lus subtilis) was planted and statically cultured at 32 ° C. to observe the growth of both bacteria. Benzoic acid 0.2% by weight as control culture
Both bacteria were inoculated into the nutrient liquid medium containing the above and the nutrient liquid medium containing neither of the preservatives and cultured in the same manner.

As is clear from the results shown in Table 1, growth of both bacteria was observed in the nutrient liquid medium containing no preservative, whereas the preservative inclusion preparations (a) and (b) of the present invention were used. It was proved to inhibit the growth of two kinds of test bacteria, and it is recognized that it shows the same bactericidal effect as benzoic acid.

[0018]

[Table 1]

Example 2 48.6 g (50 mmol) of α-cyclodextrin and 6.9 g (50 mmol) of salicylic acid were dissolved in 400 ml of water, and the mixture was stirred at room temperature for 24 hours and then cooled to precipitate. Separate and then dry under vacuum.
In addition, 9.1 g (8 mmol) of β-cyclodextrin and 1.1 g (8 mmol) of salicylic acid were dissolved in 500 ml of water, stirred at room temperature for 24 hours, cooled, and the resulting precipitate was centrifuged and then decompressed. dry. As described above, 34.0 g of α-cyclodextrin / salicylic acid inclusion preparation (c) or β-cyclodextrin /
6.5 g of salicylic acid inclusion preparation (d) is obtained.

In order to confirm that these inclusion preparations (c) and (d) have the same antiseptic and bactericidal effects as those obtained by using salicylic acid alone, the growth inhibition in bacterial culture was evaluated. Escherichia coli (Escherichia coli) was added to a nutrient liquid medium containing both inclusion preparations (c) and (d) in an amount of 1.61% by weight and 1.85% by weight (corresponding to 0.2% by weight as a salicylic acid content). And Bacillus subtilis (B
acillus subtilis) was planted and statically cultured at 32 ° C. to observe growth of both bacteria. Salicylic acid 0.2 as control culture
Both bacteria were planted in a nutrient liquid medium containing wt% and a nutrient liquid medium containing no preservative, and cultured in the same manner.

As is clear from the results shown in Table 2, growth of both bacteria was observed in the nutrient liquid medium containing no preservative, while the preservative inclusion preparations (c) and (d) of the present invention were used. It was proved to inhibit the growth of two kinds of test bacteria, and it is recognized that it shows the same bactericidal effect as salicylic acid.

[0022]

[Table 2]

Example 3 20.6 g (16 mmol) of γ-cyclodextrin and 1.0 g (8 mmol) of benzoic acid or salicylic acid 1.
Dissolve 1 g (8 mmol) in 100 ml of water,
After stirring at room temperature for 24 hours, the precipitate formed by cooling is centrifuged and then dried under reduced pressure. As above, γ
-Cyclodextrin / benzoic acid inclusion preparation (e) 9.0
g or γ-cyclodextrin / salicylic acid inclusion preparation (f), 9.5 g is obtained.

In order to confirm that these inclusion preparations (e) and (f) have the same antiseptic and bactericidal effects as those obtained when benzoic acid or salicylic acid is used alone, growth inhibition in bacterial culture is confirmed. Was evaluated. 2.32% by weight of both inclusion preparations (e) and (f), 2.0
8% by weight (0.5% as pure benzoic acid or salicylic acid.
Escherichia coli and Bacillus subtilis (Bacillus sub
tilis) was planted and statically cultured at 32 ° C. to observe the growth of both bacteria. As a control culture, both bacteria were planted in a nutrient liquid medium containing 0.2% by weight of benzoic acid or 0.2% by weight of salicylic acid, and cultured in the same manner.

As is clear from the results in Table 3, the preservative inclusion preparations (e) and (f) of the present invention were proved to inhibit the growth of two kinds of test bacteria, and benzoic acid and salicylic acid, respectively. It is recognized that the same bactericidal effect is exhibited.

[0026]

[Table 3]

Example 4 Six kinds of clathrate preparations in which α-, β- and γ-cyclodextrin were clathrated with benzoic acid and salicylic acid respectively ((a) and (b) of Example 1 and (of Example 2) In order to evaluate the skin irritation properties of (c) and (d) and (e) and (f) of Example 3, a patch test was conducted using benzoic acid and salicylic acid as controls. In the patch test, an aqueous solution of the above 6 kinds of clathrates (corresponding to 0.2% by weight as a preservative) and a 0.2% by weight aqueous solution of each of 2 control preservatives were applied to the upper arm of a panel of 11 people After 24 hours, the skin reaction was observed. As is clear from the results in Table 4, all of the preservative inclusion preparations of the present invention have reduced skin irritation and can be a preservative having excellent safety as compared with benzoic acid and salicylic acid. Admitted.

[0028]

[Table 4]

Example 5 Six kinds of clathrate preparations in which benzoic acid and salicylic acid were clathrated in α-, β- and γ-cyclodextrin ((a) and (b) in Example 1 and (( In order to confirm that c) and (d) and (e) and (f) of Example 3 exhibit antiseptic and bactericidal effects even in the presence of an anionic surfactant, which is a shampoo washing component, Growth inhibition in cell culture was evaluated. 0.2% by weight of each of the above 6 types of inclusion preparations was added as a preservative to a nutrient liquid medium containing 5% by weight of sodium polyoxyethylene lauryl sulfate, and Escherichia coli and Bacillus subtilis Were planted and statically cultured at 32 ° C. to observe the growth of both bacteria. As a control culture, both bacteria were inoculated in a liquid obtained by dissolving 0.2% by weight of benzoic acid or 0.2% by weight of salicylic acid in a nutrient liquid medium containing 5% by weight of sodium polyoxyethylenelauryl sulfate, and cultured in the same manner. Both bacteria were planted and cultured in a nutrient liquid medium containing 5% by weight of sodium polyoxyethylene lauryl sulfate without dissolving any preservative.

As is clear from the results in Table 5, the growth of bacteria was observed in the medium containing no preservative, while the inclusion preparations (a), (b) and (e) which are the preservatives of the present invention. )
In, it was proved that the growth of two kinds of test bacteria was inhibited, and it was recognized that it showed the same bactericidal effect as benzoic acid. Further, it is recognized that the inclusion preparations (c), (d) and (f) show the same bactericidal effect as that of salicylic acid.

[0031]

[Table 5]

Example 6 13.6 g (14 mmol) of α-cyclodextrin and 2.0 g (14 mmol) of sodium benzoate were added to 20 parts of water.
Dissolve in 0 ml, stir at room temperature for 24 hours, evaporate water under reduced pressure and centrifuge the resulting precipitate,
Then, it is dried under reduced pressure. In addition, α-cyclodextrin 1
3.6 g (14 mmol) and sodium salicylate 2.
2 g (14 mmol) is dissolved in 200 ml of water, stirred at room temperature for 24 hours, evaporated under reduced pressure to evaporate water, and the resulting precipitate is centrifuged and then dried under reduced pressure.
As described above, 10.0 g of α-cyclodextrin / sodium benzoate inclusion preparation (g) or α-cyclodextrin / sodium salicylate inclusion preparation (h) 11.
3 g are obtained.

9.2 g (8.3) of β-cyclodextrin
Mmol) and 1.2 g (8.3 mmol) of sodium benzoate were dissolved in 500 ml of water, and the solution was allowed to stand at room temperature for 24 hours.
After stirring for a period of time, the mixture is cooled and the resulting precipitate is centrifuged and then dried under reduced pressure. Also, 9.2 g (8.3 mmol) of β-cyclodextrin and 1.3 g (8.3 mmol) of sodium salicylate were dissolved in 500 ml of water, and the mixture was stirred at room temperature for 24 hours and cooled to precipitate the resulting precipitate. Separate and then dry under vacuum. As described above, 7.3 g of β-cyclodextrin / sodium benzoate inclusion preparation (i) or β-cyclodextrin /
6.0 g of sodium salicylate inclusion preparation (j) is obtained.

Γ-cyclodextrin 18.2 g (14
Mmol) and 1.0 g (7 mmol) of sodium benzoate are dissolved in 100 ml of water, stirred at room temperature for 24 hours, evaporated under reduced pressure to evaporate water, and the resulting precipitate is centrifuged and dried under reduced pressure. Further, 18.2 g (14 mmol) of γ-cyclodextrin and 1.1 g (7 mmol) of sodium salicylate were dissolved in 100 ml of water, stirred at room temperature for 24 hours, and then evaporated under reduced pressure to evaporate the resulting precipitate. Separate and then dry under vacuum. As described above, γ-cyclodextrin / sodium benzoate inclusion preparation (k) 13.2 g or γ-cyclodextrin / sodium salicylate inclusion preparation (l)
13.5 g are obtained.

These inclusion preparations (g), (h),
(I), (j), (k), (l) and (a) of Example 1.
And (b), (c) and (d) of Example 2 and (e) and (f) of Example 3 show the antiseptic and bactericidal effect when compounded in shampoo. The antiseptic and bactericidal effect was evaluated.

Shampoos shown in Formulation 1, Formulation 2 and Formulation 3 of Table 6 were produced. To the shampoos of prescription 1, prescription 2 and prescription 3, the above 12 kinds of clathrates are added as preservatives in an amount of 0.2.
E.coli (Escherichia coli)
Were planted and statically cultured at 32 ° C. to observe growth.

As control cultures, Escherichia coli (Escherichia coli) was planted in shampoos of Formula 1, Formula 2 and Formula 3 without any antiseptic fungicide added, and the same culture was performed to observe growth. In addition, the shampoo of the prescription 1, benzoic acid,
0.2% by weight each of salicylic acid, sodium benzoate and sodium salicylate was added to E. coli (Escherichi
a.coli) was planted and cultured in the same manner, and the growth was observed. Similarly to the prescription 1, shampoos of the prescription 2 and the prescription 3 were mixed with benzoic acid, salicylic acid, sodium benzoate, and sodium salicylate in an amount of 0.2% by weight, respectively.
cherichia coli) was planted and cultured in the same manner, and the growth was observed.

As is clear from the results in Table 7, bacterial growth was observed in the shampoo containing no preservative, whereas the preservative inclusion preparations (a), (b), and (e) of the present invention were found to grow. In, it was proved that the growth of the test bacteria was inhibited, and it was recognized that it showed the same bactericidal effect as benzoic acid. It is recognized that the inclusion preparations (c), (d) and (f) show the same bactericidal effect as salicylic acid. It is recognized that the inclusion preparations (g), (i) and (k) show the same bactericidal effect as that of sodium benzoate. It is recognized that the inclusion preparations (h), (j) and (l) show the same bactericidal effect as that of sodium salicylate.

[0039]

[Table 6]

[0040]

[Table 7]

Example 7 Twelve clathrate formulations (a), (b) used in Example 6,
(C), (d), (e), (f), (g), (h),
Emulsions of (i), (j), (k), and (l) were added to shampoos of prescription 1, prescription 2, and prescription 3 as preservatives in an amount of 0.05% by weight, which is the minimum amount in the present invention. (Escherichia coli) was planted and statically cultured at 32 ° C. to observe growth. The control culture was omitted because it is the same as the control culture of Example 6.

As is clear from the results shown in Table 8, the preservative inclusion preparations (a), (b) and (e) of the present invention were proved to inhibit the growth of the test bacteria, and benzoic acid It is recognized that the same bactericidal effect is exhibited. Inclusion preparation (c),
In (d) and (f), it is recognized that the same bactericidal effect as that of salicylic acid is exhibited. It is recognized that the inclusion preparations (g), (i) and (k) show the same bactericidal effect as that of sodium benzoate. It is recognized that the inclusion preparations (h), (j) and (l) show the same bactericidal effect as that of sodium salicylate.

[0043]

[Table 8]

Example 8 Twelve clathrate formulations (a), (b) used in Example 6,
(C), (d), (e), (f), (g), (h),
(I), (j), (k) and (l) were added to the shampoos of Formula 1, Formula 2 and Formula 3 as preservatives, each being 1.0% by weight which is the maximum amount of the compounded amount in the present invention, Escherichia coli was planted and statically cultured at 32 ° C. to observe growth. The control culture was omitted because it is the same as the control culture of Example 6.

As is clear from the results shown in Table 9, the preservative inclusion preparations (a), (b) and (e) of the present invention were proved to inhibit the growth of the test bacteria, and benzoic acid It is recognized that the same bactericidal effect is exhibited. Inclusion preparation (c),
In (d) and (f), it is recognized that the same bactericidal effect as that of salicylic acid is exhibited. It is recognized that the inclusion preparations (g), (i) and (k) show the same bactericidal effect as that of sodium benzoate. It is recognized that the inclusion preparations (h), (j) and (l) show the same bactericidal effect as that of sodium salicylate.

[0046]

[Table 9]

Example 9 2 out of the cyclodextrin / benzoic acid clathrate, the cyclodextrin / salicylic acid clathrate, the cyclodextrin / sodium benzoate clathrate or the cyclodextrin / sodium salicylate clathrate shown in claim 1 In order to confirm that when mixing more than one seed and blending in shampoo, it shows the same antiseptic bactericidal effect as the preservative that is not included. evaluated.

A shampoo having a formulation 2 shown in Table 6 of Example 6 was produced, and as shown in Table 10, an inclusion preparation mixed in a ratio that is the minimum amount in the present invention was mixed, and Escherichia coli was added. Planting and static culture at 32 ° C. were observed for growth.

As a control culture, a shampoo of Formula 2 was added,
Escherichia coli (Escherichia
coli) was planted and cultured in the same manner, and the growth was observed. Also,
Benzoic acid, salicylic acid, sodium benzoate, and sodium salicylate were added to the shampoo of Formulation 2 at the ratios shown in Table 11, Escherichia coli was planted, and the same culture was performed to observe the growth.

As is clear from the results shown in Table 12, bacterial growth was observed in the shampoo containing no preservative, whereas when the preservative inclusion preparation of the present invention was mixed and mixed,
It is recognized that all of them have the same antiseptic and bactericidal effect as that of unencapsulated benzoic acid, salicylic acid, sodium benzoate or sodium salicylate.

[0051]

[Table 10]

[0052]

[Table 11]

[0053]

[Table 12]

Example 10 As shown in Tables 13 and 14, only the compounding amount of the preservative clathrate preparation is 0.2% by weight, which is the upper limit for compounding benzoic acid or salicylic acid into shampoos in Japan. Was changed to and tested in the same manner as in Example 9.

As is clear from the results shown in Table 15, bacterial growth was observed in the shampoo containing no preservative, whereas when the preservative clathrate of the present invention was mixed and mixed,
It is recognized that all of them have the same antiseptic and bactericidal effect as that of unencapsulated benzoic acid, salicylic acid, sodium benzoate or sodium salicylate.

[0056]

[Table 13]

[0057]

[Table 14]

[0058]

[Table 15]

Example 11 A test was conducted in the same manner as in Example 9 except that the inclusion amount of the preservative inclusion preparation was set to 1.0% by weight, which is the upper limit of the present invention, as shown in Tables 16 and 17.

As is clear from the results in Table 18, bacterial growth was observed in the shampoo containing no preservative, whereas when the preservative inclusion preparation of the present invention was mixed and formulated,
It is recognized that all of them have the same antiseptic and bactericidal effect as that of unencapsulated benzoic acid, salicylic acid, sodium benzoate or sodium salicylate.

[0061]

[Table 16]

[0062]

[Table 17]

[0063]

[Table 18]

Claims (2)

[Claims] 1. A molecule of one cyclodextrin selected from α-, β-, or γ-cyclodextrin contains one of benzoic acid, salicylic acid, sodium benzoate and sodium salicylate as a preservative. Cyclodextrin / benzoic acid clathrate (1), cyclodextrin / salicylic acid clathrate (2), cyclodextrin / sodium benzoate clathrate (3) or cyclodextrin / sodium salicylate clathrate (4) ) Is added to a shampoo as an antiseptic in the range of 0.05 to 1.0% by weight, and a preservative inclusion preparation for shampoo. 2. A mixture of two or more of the inclusion preparations (1) to (4) according to claim 1, which together serve as a preservative within a range of 0.05 to 1.0% by weight, A preservative inclusion preparation for shampoo, which is blended with shampoo.