JPH0230360B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing hyposensitizing and hypoallergenic diasmine oil. [Prior Art] Conventionally, natural diasmine oil is one of the most well-known and widely used natural essential oils as a fragrance material for cosmetics, but it has been pointed out that it has sensitizing properties. [Nakayama et al., Koshokai Journal,
3 (No. 2) 23-35 (1980)]. Therefore, there have been problems when using it as a fragrance ingredient in cosmetics such as perfumes, creams, and milky lotions that are applied directly to the skin. [Problem to be solved by the invention] By the way, natural diasmine oil is composed of dozens of components, but only a limited number of these components actually have sensitizing or irritating properties. It is thought to be some substances. Therefore, if these sensitizing and irritating substances can be selectively removed, highly safe diasmine oil that is virtually free of sensitizing and irritating properties can be obtained. On the other hand, distillation may be considered to remove these sensitizing and irritating substances, but the aroma components in natural diasmine oil generally have poor thermal stability, and if the distillation temperature is high, important aroma components may deteriorate. However, there is a problem in that the quality of the aroma is significantly impaired. [Means for Solving the Problems] As a first step, the present inventors conducted fractionation using vacuum distillation, molecular distillation, column chromatography, etc. in order to identify the sensitizing substances present in natural diasmine oil. The relationship between each component in natural diasmine oil and its sensitization properties was investigated in detail using a combination of research and sensitization tests in animals. That is, natural diasmine oil is fractionated using the method described above, and each component is separated using preparative gas chromatography in order to more closely examine the sensitizing portion. Identification was performed using an analytical method. As a result, the main causes of the sensitizing properties of natural diasmine oil were eugenol and benzyl salicylate, which were previously known as sensitizing phenols [Yamamoto et al., Skin, 23 (No. 6) 762-769 (1981)]. ] was confirmed. [Formula] [Formula] Next, as a second step, the present inventors continued to conduct intensive studies to selectively remove sensitizing phenols from natural diasmine oil. Using physical means, it is fractionated into a part that does not contain sensitizing phenols and a part that contains sensitizing phenols, and the part that contains sensitizing phenols is combined with a nonpolar solvent and an alkaline aqueous solution. Sensitizing phenols are removed by treatment under mild conditions.
After that, by combining the treated oil obtained by distilling off the solvent with the part that does not contain sensitizing phenols, the aroma of natural diasmine oil can be reproduced well, and sensitizing phenols can be produced industrially and economically. He discovered that it was possible to obtain diasmine oil from which diasmine oil had been removed, and filed a patent application (Japanese Patent Application No. 46373/1983). Now, in the present invention, as a result of intensive research to further investigate the safety of natural diasmine oil on the skin, we have developed a method that uses highly irritating diterpene alcohols (isophytol, phytol, and geranyl linalool). By acetalizing the containing portion with ethyl vinyl ether under acidic conditions, we succeeded in obtaining diasmine oil with significantly reduced irritation. Safety is an issue with fragrances that come into direct contact with the human body, such as cosmetic fragrances, and evaluation methods include primary irritation evaluation method, cumulative irritation evaluation method,
There are sensitization evaluation methods, mucosal irritation evaluation methods, patch tests, etc. Among these, sensitization and cumulative irritation are particularly important. Low sensitization is an important requirement for cosmetic fragrances, and low cumulative irritation is an especially important requirement for products that are used daily, such as cosmetics. Fragrances are also required to have low cumulative irritation. In this way, in order to obtain safer diasmine oil, we have further improved the previously applied technology to create a low-sensitizer that has good reproducibility of the aroma as natural diasmine oil, is industrially advantageous, and is inexpensive. The present invention was completed based on the discovery that diasmine oil can be obtained with mild and hypoallergenic properties. That is, in the present invention, natural diasmine oil is distilled under reduced pressure at a temperature of 130° C. or less and a degree of vacuum of 2 mmHg or less, using natural diasmine oil as a first step, to obtain an initial first fraction, a second fraction,
fractionating into a third fraction and a first residue fraction, distilling eugenol only in the second fraction, and leaving benzyl salicylate, isophytol, phytol and geranyl linalool only in the first residue fraction, As a second step, the first residue fraction is subjected to molecular distillation under the conditions of a temperature of 120° C. or less and a degree of vacuum of 2×10 ^-2 mmHg or less, and is fractionated into a fourth fraction and a second residue fraction; Benzyl salicylate, isophytol, phytol, and geranyl linalool are distilled out only from the four fractions, and in the third step, the second fraction is dissolved in a nonpolar solvent and added to an aqueous solution of sodium hydroxide and/or potassium hydroxide. After washing with an alkali, the liquid is separated, and the non-polar solvent layer is separated and washed with water.The non-polar solvent is then distilled off to obtain a first residual oil, and in the fourth step, the fourth fraction is After reacting with ethyl vinyl ether under acidic conditions, the reaction solution was dissolved in a nonpolar solvent, washed with water, neutralized with an aqueous alkali solution, and further neutralized with an aqueous solution of sodium hydroxide and/or potassium hydroxide. After washing, the liquid is separated, and the nonpolar solvent layer is separated and washed with water. The nonpolar solvent and excess ethyl vinyl ether are distilled off to obtain a second residual oil.
As a fifth step, the initial first distillate, third distillate,
The present invention relates to a method for producing hyposensitizing and hypoallergenic diasmine oil, which is characterized by combining a second residual oil component, a first residual oil component, and a second residual oil component. The conditions for vacuum distillation in the present invention must be such that they do not alter the aroma components of natural diasmine oil; the temperature is 130°C or less, the degree of vacuum is mmHg.
The following is preferable. In addition, the high boiling point portion is distilled by molecular distillation. The conditions for molecular distillation are preferably a temperature of 120° C. or less and a degree of vacuum of 2×10 ^-2 mmHg or less. Natural diasmine oil is distilled and fractionated under the conditions of vacuum distillation and molecular distillation described above, and sensitizing phenols and
The portion containing diterpene alcohols, that is, the second fraction containing eugenol, and the first residue portion containing benzyl salicylate, isophytol, phytol, and geranyl linalool are subjected to the next step. It should be noted that in order to minimize loss due to removal of important aroma components during the distillation process, fractions containing sensitizing phenols and irritating diterpene alcohols should be The goal is to set distillation conditions that minimize the amount of sensitizing phenols and maximize the concentration of irritating diterpene alcohols. Next, the second fraction containing eugenol, which is a sensitizing substance, is dissolved by adding a nonpolar solvent and washed with alkali by adding an aqueous alkaline solution. Further, the fourth fraction containing benzyl salicylate, which is a sensitizing substance, is also subjected to alkaline washing in the same manner. As the nonpolar solvent, for example, aliphatic hydrocarbons such as pentane, isopentane, hexane, heptane, octane, and cyclohexane can be used.
Particularly preferred are pentane, isopentane, and hexane. The amount of solvent to be used is 1 to 10 times the weight of the part to be treated, preferably 2 to 5 times the weight. In addition, the alkaline agent used in alkaline cleaning treatment to form adducts with sensitizing phenols is sodium hydroxide and/or potassium hydroxide, and the aqueous solution used is at a concentration of 1 to 5 percent by weight. but preferably 2 to 3 weight percent. When the concentration is increased, the reaction conditions are relaxed by increasing the amount of nonpolar solvent used so as not to change the other components. The amount of the alkaline aqueous solution used is preferably 3 to 10 times the amount of sensitizing phenols to be treated.
The reaction between the sensitizing phenols and the alkaline agent is accomplished by stirring at room temperature for about 1 to 2 hours. Next, the reaction solution is allowed to stand, the solvent layer is separated, washed with water, dried, and then the solvent is distilled off to obtain a treated oil that does not contain sensitizing phenols. The second fraction is treated in this manner to obtain the first residual oil fraction. Further, the fourth fraction containing diterpene alcohols is treated with ethyl vinyl ether under acidic conditions, for example in the presence of phosphoric acid, hydrochloric acid, sulfuric acid, etc., to produce an acetaldehyde ethyl acetal compound of diterpene alcohols. The amount of ethyl vinyl ether used to form the compound with the diterpene alcohol is between 2 and 5 of the diterpene alcohol to be reacted.
It is preferable to use twice the molar amount. The reaction is achieved by stirring for about 1 to 3 hours at a reaction temperature of 10 to 60°C. Next, a nonpolar solvent such as aliphatic hydrocarbons such as hexane, heptane, and benzene is added to the reaction solution, which is washed with water, neutralized with a 5 to 10% by weight aqueous sodium carbonate solution, washed with water, and dried. By distilling off the solvent and excess ethyl vinyl ether, a treated oil containing an acetaldehyde diterpenylethyl acetal compound with significantly reduced irritation is obtained. For the fourth fraction containing sensitizing phenols and diterpene alcohols, both the step of applying ethyl vinyl ether and the step of treating with alkali are carried out, but the order of these steps does not matter. A second residual oil component is obtained by processing in this manner. These treated oils thus obtained, that is, the first residual oil fraction and the second residual oil fraction, are divided into the fraction containing no sensitizing phenols and irritating diterpene alcohols obtained by the above fractionation, that is, the initial first fraction. , the third distillate and the second residue fraction to substantially remove the sensitizing substances, namely eugenol and benzyl salicylate, and to make the irritating substances, namely isophytol, phytol and geranyl linalool non-irritating. A diasmine oil is obtained which is converted into a substance, namely the respective acetaldehyde ethyl acetal compound, which is a hyposensitizing and hypoallergenic diasmine oil. In addition, in the above fractionation operation, the distillation or presence or absence of sensitizing substances and irritating substances can be confirmed using an appropriate analytical method such as gas chromatography. As described above, according to the present invention, sensitizing substances and irritating substances can be easily removed from natural diasmine oil without causing any adverse effects on the aroma, ingredients, etc. of natural diasmine oil, and also industrially. can. When combining, all or part of the parts that do not contain sensitizing phenols that have been subdivided according to the fractionation conditions may be used in an appropriate amount depending on the purpose, and furthermore, they may be used as appropriate to enhance the aroma. Other aroma ingredients may also be added. EXAMPLES Next, the method of the present invention will be explained in more detail with reference to Examples. [Example] Egyptian natural diasmine oil (eugenol)
1.67%, benzyl salicylate 0.03%, isophytol 4.75%, phytol 11.55%, geranyl linalool 3.29%) 200g as the first step,
It was distilled under reduced pressure and fractionated as follows. Initial first fraction: Fraction A (cooling trap collection fraction) 2g Fraction B (boiling point 53℃ or less/0.8mmHg 51g Second fraction: Fraction C (boiling point 59-80℃/0.6mmHg: contains eugenol) 14g Third fraction: Fraction D (boiling point over 80~112℃/0.6mmHg) 10g First residue: Residue R- (contains benzyl salicylate, isophytol, phytol, geranyl linatol) 120g Then, as a second step, Above residue R-120
g was subjected to molecular distillation at a reduced pressure of 1.5 x 10 ^-3 mmHg and fractionated as follows. Fourth fraction: Fraction E (boiling point below 90℃/1.5× ^{10 -3} mmHg: contains benzyl salicylate, isophytol, phytol, geranyllinalool) 64g Second residue: Residue R- 55g (vacuum distillation and molecular distillation) (The total loss was 4 g.) In the third step, 14 g of fraction C (containing eugenol) obtained by the above fractionation was dissolved in 100 ml of hexane, and 150 g of a 3% by weight aqueous sodium hydroxide solution was added.
was added and stirred vigorously at room temperature for 1 hour. After stirring, the reaction solution was allowed to stand and separated to obtain a hexane solution layer, which was washed with water and dried over sodium sulfate, and then the hexane was distilled off under reduced pressure to obtain 10 g of treated oil. As a result of analyzing fraction C and treated oil X by gas chromatography,
Eugenol found in fraction C was not found in treated oil X. (Figures 1 and 2) Next, in the fourth step, 64 g of fraction E (containing benzyl salicylate, isophytol, phytol, and geranyl linalool) and ethyl vinyl ether
Charge 29 g and 0.5 g of 85% by weight phosphoric acid aqueous solution into a 500 ml four-necked flask equipped with a stirrer, thermometer, and reflux condenser. Then stir vigorously for about 2 hours. At this time, the reaction temperature is maintained at 20-50°C. After the reaction was completed, the reaction solution was dissolved in 100 ml of hexane, washed with water, neutralized with a 10% by weight aqueous sodium carbonate solution, and then treated with a 3% by weight aqueous sodium hydroxide solution. After the treatment, the reaction solution was allowed to stand, and the layers were separated to obtain a hexane solution layer, which was washed with water and dried with sodium sulfate. Hexane and excess ethyl vinyl ether were distilled off under reduced pressure.
Processed oil Y was obtained. As a result of analyzing fraction E and treated oil Y by gas chromatography, the diterpene alcohols found in fraction E were found in treated oil Y in the form of acetalization. (Figure 3,
(Figure 4) Also, confirmation of removal of benzyl salicylate was confirmed by gas chromatography/mass spectrometry. Finally, in the fifth step, by combining fraction A, fraction B, fraction D, residue R-, treated oil X, and treated oil Y, sensitizing phenols and highly irritating diterpene alcohol 184 g of hyposensitizing and hypoallergenic diasmine oil from which the substances were removed was obtained. Moreover, the final yield was 92%, which was extremely high. The presence of distillate substances, sensitizing substances, and irritating substances in each of the above-mentioned operation steps was confirmed by gas chromatography analysis under the following conditions. (Equipment used and its conditions) Model: Shimadzu GC-5A Column: PEG20M (5%) 3 mm x 2 m Column temperature: 210°C (temperature raised from 100°C at 5°C/min) Carrier gas: Helium gas flow rate 35ml/min Detector: Hydrogen ion flame detector (FID) The diasmine oil obtained by the production method of the present invention, in which sensitizing phenols have been removed and irritating diterpene alcohols have been acetalized, is produced by Magnutsson and Kriegman's Guinea Bitsug, Maximi Guinea Pig Maximization
According to the sensitization test conducted in accordance with the Test) Act,
Although it was found that sensitization was definitely reduced,
At the same time, a cumulative skin irritation test revealed that the skin cumulative irritation was significantly reduced. The cumulative skin irritation test is shown below. In the skin cumulative irritation test, the Draize method was used to
Five domestic rabbits weighing 2.5 to 3.0 kg were used and the samples were applied continuously for two weeks. The average value of the reaction was determined according to the criteria and was used as a score. The results are shown in Table 1. The samples used in this test were those obtained by the method shown in Examples. [Table] [Table] As described above, the diasmine oil obtained according to the present invention was found to be a low sensitizing and low irritation diasmine oil. Examples of formulations in which the low sensitizing and hypoallergenic diasmine oil obtained by the present invention are blended with other aromatic components are shown below. In addition, the compounding ratio in the preparation example is shown in parts by weight. [Preparation example] Fraction A (cooling trap collection) 1.0 Fraction B (distillation section) 25.5 Fraction D (distillation section) 5.0 Residue R- 27.5 Processed oil X (desensitizing phenol) 5.0 Treated oil Y (desensitizing phenol and desirmating diterpene alcohol) 27.5 Methyl dihydrodiasmonate 2.0 Cis-diasmonate 0.65 Cis-3-hexenyl benzoate 0.25 Indole 0.75 Acetaldehyde phytylethyl acetal
1.0 Acetaldehyde isophyl ethyl acetal 2.3 Acetaldehyde geranyl linalyl ethyl acetal 0.7 Squalene 0.25 Others (raw materials for odor correction) 0.6 Total 100.0 [Effects of the invention] As detailed above, according to the production method of the present invention, natural diasmine oil The sensitizing substances eugenol and benzyl salicylate can be easily removed from natural diasmine oil without any risk of adversely affecting the fragrance, ingredients, etc., and the irritating substances isophytol, phytol, and geranyl linalool can be removed from natural diasmine oil. Since it is converted into a non-irritating substance through acetalization, it is possible to obtain a hyposensitizing and hypoallergenic diasmine oil with a reproducible aroma.

[Brief explanation of drawings]

Figure 1 is the gas chromatogram of fraction C (eugenol-containing) in the example, Figure 2 is the gas chromatogram of the treated oil FIG. 4 is a gas chromatogram of treated oil Y in Example. Each numbered peak in the figure indicates the following components. 1... Eugenol, 2... Isophytol,
3...Geranyllinalool, 4...Phytol,
5... Acetaldehyde isophyl ethyl acetal, 6... Acetaldehyde geranyl linally ethyl acetal, 7... Acetaldehyde phythyl ethyl acetal, the horizontal axis in each figure shows the retention time (minutes).

Claims (1)

[Claims] 1. Using natural diasmine oil as the first step, temperature
Distillation is carried out under reduced pressure at a temperature of 130°C or lower and a degree of vacuum of 2 mmHg or lower, and fractionated into an initial first fraction, a second fraction, a third fraction, and a first residue, and eugenol is added only to the second fraction. In addition, benzyl salicylate, isophytol, phytol, and geranyl linalool remain only in the first residue, and in a second step, the first residue is distilled at a temperature of 120°C or less.
Molecular distillation is carried out under reduced pressure conditions of 2×10 ^-2 mmHg or less,
The second fraction is fractionated into a fourth fraction and a second residue fraction, and benzyl salicylate, isophytol, phytol, and geranyl linalool are distilled out only in the fourth fraction, and as a third step, the second fraction is made into a nonpolar fraction. After dissolving in a solvent and washing with an alkali solution of sodium hydroxide and/or potassium hydroxide, the layers are separated, and the non-polar solvent layer is separated, washed with water, and the non-polar solvent is distilled off. to obtain the first residual oil content,
In the fourth step, the fourth fraction is treated with ethyl vinyl ether under acidic conditions, the reaction solution is dissolved in a non-polar solvent, washed with water, neutralized with an alkaline aqueous solution, and further treated with sodium hydroxide. And/or after alkaline washing with an aqueous potassium hydroxide solution, the layers are separated, and the nonpolar solvent layer is separated and washed with water, and the nonpolar solvent and excess ethyl vinyl ether are distilled off to obtain a second residual oil. As a fifth step, the initial first distillate, third distillate, second residue fraction,
A method for producing hyposensitizing and hypoallergenic diasmine oil, which comprises combining a first residual oil component and a second residual oil component.