JP2006143659A - External preparation for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation for skin that has anti-itching effect, originates from a natural plant with reduced side effect and has high drug action durability. <P>SOLUTION: An essence extracted from a plant, Impatiens balsamina, is added to a camellia oil, particularly from a wild common camellia whereby the persistence of the pharmaceutical effect can be elongated with no adverse effect to the anti-itching effect derived from the essence of Impatiens balsamina. The effect of camellia oil is superior to the effect of other natural moisture retention agents. This external preparation for skin also can be used in the form of gel, cream, milk and the like. In addition, it can arbitrarily be combined with other known natural pharmaceutical components, for example, having anti-allergic effect, anti-inflammatory effect or the like, and can provide a wide variety of external preparations. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an external preparation for skin, particularly an external preparation for allergic dermatitis typified by atopic dermatitis, and more specifically, has an itching inhibiting action, an inflammation inhibiting action, an antiallergic action, and The present invention relates to a skin external preparation with few side effects.

  In recent years, patients with allergic diseases such as atopic dermatitis, food allergies, sick house syndrome, and hay fever are increasing year by year due to changes in living environment. All of these are associated with persistent itching, causing pain to the patient and scratching the affected area further exacerbating the symptoms. Indispensable for treatment.

  Various agents have been provided as anti-itch agents so far. Antihistamines that are antagonists of histamine known as causative agents for allergies and antiallergic agents containing histamine are the most common. However, antihistamines and antiallergic agents are associated with side effects such as drowsiness, lightheadedness, and stomach problems.

  In order to solve such problems, various anti-itching agents and anti-inflammatory agents derived from natural products have been proposed. Prior Document 1 (Patent Document 1: Japanese Patent Laid-Open No. 9-255583), Prior Document 2 (Patent Document 2: Japanese Patent Laid-Open No. 2000-26447), Prior Document 3 (Patent Document 3: Japanese Patent Laid-Open No. 2000-239161) Specific flavonoid compounds, naphthoquinone compounds, naphthoquinone derivatives or dinaphthofuran quinone derivatives isolated from extract of the spinach (Impatiens balsamina L.) and anti-itch agents and allergic diseases containing these compounds as active ingredients A therapeutic agent is described.

Further, in the prior art document 4 (Patent Document 4: Japanese Patent Laid-Open No. 11-322620), an external preparation using a combination of a spinach extract and propolis is disclosed, and in the prior art document 5 (Patent Document 5: Japanese Patent Laid-Open No. 2000-44481). The topical skin preparations are described in which extract extracts such as mugwort, aloe, carrot and rosemary are blended with the spinach extract.
However, the compounds isolated from the extract of the spinach as described above have problems in their sustainability, such as those that have a pharmacological effect against allergic diseases such as atopic dermatitis, but may be dried immediately. The development of a topical skin preparation with improved sustainability has been eagerly desired.
JP-A-9-255583 JP 2000-26447 A JP 2000-239161 A JP-A-11-322620 JP 2000-44481 A

  Each of the inventions described in the above-mentioned prior art documents provides an external preparation for skin that has an anti-itching effect and an anti-allergic effect and has few side effects. However, the duration of the pharmacological effect on the affected area is not sufficient, and it is sustained by allergy. When coping with physical and chronic itching, continuous drug administration was necessary.

  However, even if the drug is administered continuously, in the case of an external preparation with a short pharmacological effect, the pharmacological effect generally decreases before the next dose, and itch is perceived at that time. It cannot be avoided. On the other hand, the next administration while the pharmacological effect is sufficiently sustained has the adverse effect of causing excessive intake of the drug to the human body. In addition, when dealing with chronic itching, a large number of daily dosing operations means troublesome work, and if the dosing operation is difficult such as when going out, the continuity of dosing will be interrupted. There were problems such as.

  These problems are caused by the fact that the conventional external preparation having an anti-itching effect as described above does not have a sufficient duration of pharmacological effect.

  Therefore, in view of the circumstances as described above, the object of the present invention is to have an anti-itching effect against allergic dermatitis typified by atopic dermatitis, has few side effects, and has a long duration of pharmacological effect. It is to provide an agent.

  Therefore, in order to solve the above problems, the present inventors, as a result of intensive studies, by adding camellia oil to the extract of the spinach (Impatiens balsamina L.), without impairing the anti-itching effect derived from the spinach extract In addition, it has been found that the pharmacological effect can be sustained in the affected area for a long time, and based on such knowledge, it is applied to a topical skin preparation having a side effect derived from a natural product and having an anti-itching effect and an anti-inflammatory effect. The present invention has been completed.

In particular, the correlation between the camellia oil component, which is said to have a moisturizing effect on the skin, and the persistence of the pharmacological effect of other components such as the extract of spinach, etc. has not been known so far, and the component has a moisturizing effect derived from natural products. In addition to camellia oil, there are many sugar alcohols such as glycerin and natural moisturizing factors (NMF) such as amino acids. The present inventors have found that camellia oil is optimal as a blending component that can be applied, and have come up with the present invention relating to an external preparation for skin, after repeated trials.
That is, the flavonoid compounds isolated from the extract of spinach are shown to have an anti-anaphylactic activity effect and are known to have an anti-itching effect and an anti-allergic effect. Camellia oil was generally used as hair oil or edible oil. However, it has not been clarified so far what influence the effect of the ingredients have on the affected area when the camellia oil is mixed with other medicinal ingredients.

Thus, according to the present invention,
An external preparation for skin characterized by comprising an extract of spinach and camellia oil is provided.

The present invention also includes the following related inventions as specific embodiments thereof.
(1) The skin external preparation, wherein the camellia oil is Camellia japonica L. camellia oil.
(2) The skin external application content of the extract of the spinach is 1 to 20% by weight with respect to the skin external preparation, and the content of the camellia oil is 1% by weight or more with respect to the skin external preparation. Agent.
(3) The external preparation for skin, wherein the amount of the camellia oil is 0.05 to 0.5 times by weight with respect to the extract of the spinach.

  Each of the external preparations for skin according to the present invention is characterized by containing an extract of spinach and a camellia oil that are derived from natural products as main medicinal ingredients. As a result, there are few side effects and the duration of the pharmacological effect on the affected area is prolonged. For example, even for allergic persistent and chronic itch symptoms, the anti-itch effect can be fully enjoyed with a small number of doses. be able to. Therefore, because it is an external preparation for skin, many situations where it is difficult to administer medication in daily life can be assumed, such as moving, etc. According to the present invention, the number of medications can be reduced as much as possible due to the long duration of drug efficacy. Is possible. Therefore, it is possible to reduce a mental burden on the patient due to repeated complicated medication operations and to prevent excessive intake of drugs.

  Further, the external preparation for skin according to the present invention can take various forms such as gels, creams, and emulsions, and appropriately contains other medicinal ingredients derived from natural products having known anti-allergic and anti-inflammatory effects. Therefore, various external preparations can be provided. In particular, since it is desirable for atopic dermatitis to exclude a surfactant, a gel form that does not require a surfactant is particularly preferable.

Embodiments of the present invention will be described below.
The external preparation for skin according to the present invention comprises an extract of spinach, camellia oil and, if necessary, other ingredients.

  The spinach (scientific name; Impatiens balsamina L.) is an annual plant of the genus Periwinkle and is native to Southeast Asia. From late summer to mid-autumn, red, white and light red flowers are added to the leaves. In the external preparation for skin according to the present invention, any one or more of petals, leaves, stems, pericarps, or whole plants (hereinafter referred to as “active substance”) is cut, and an extract is extracted with a solvent. Is blended. The raw material may be undried or once dried, and the order of the drying step and the cutting step is not particularly limited. In addition, any color such as red, white, light red and purple can be suitably used regardless of the petal color. Even if the components of the extract from the petals of the spinach and the extract of the stem are different from each other, the extract of the spinach of the external preparation for skin according to the present invention contains at least one of the following medicinal components and is extracted at the same time. Those containing various components are preferred.

The extract of the spinach used as a component of the external preparation for skin according to the present invention preferably contains a medicinal component represented by the following structural formulas (I) to (XII).
That is,
2,2'-ethylidene-bis (3-hydroxy-1,4-naphthoquinone) (I),
2,2'-methylene-bis (3-hydroxy-1,4-naphthoquinone) (II),
2- (1-hydroxyethyl) -3-methoxy-1,4-naphthoquinone (III),
2-Hydroxy-1,4-naphthoquinone (sometimes called Lawson) (IV),
2-methoxy-1,4-naphthoquinone (V),
Kaempferol (VI),
Quercetin (VII),
Ferulic acid (VIII),
Scopoletin (IX),
p-Coumaric acid (X),
p-Hydroxybenzoic acid (XI),
Dinaphthofuranquinone derivatives (5-hydroxy-6-methoxy-dinaphtho [1,2-b: 2 ',
3'-d] furan-7,12-dione and 5-β-D-glucosyloxy-6-methoxy-dinaphtho
[1,2-b: 2 ', 3'-d] furan-7,12-dione) (XII)
Etc.

  The solvent for extracting the extract from the raw material of the spinach is not particularly limited as long as it can extract each of the above-mentioned active ingredients, and the type thereof is not particularly limited, and the temperature is also determined. Extraction is performed at room temperature or under heating.

  Water as the polar inorganic solvent, lower alcohols such as methanol, ethanol and butanol as the polar organic solvent, for example, monohydric alcohols having 1 to 8 carbon atoms, ethylene glycol, propylene glycol, ethylene glycol monomethyl ether, propylene glycol monoethyl C2-C6 polyhydric alcohols such as ethers and derivatives thereof, ketones such as acetone and methyl ethyl ketone, esters such as methyl acetate and ethyl acetate, ethers such as diethyl ether and methyl ethyl ether, chloroform, dichloromethane and the like Halogenated hydrocarbons and nonpolar organic solvents include hydrocarbons such as toluene and benzene. In addition, these solvents can be used by appropriately mixing them.

  Of the above-mentioned solvents, water, methanol, ethanol, 1,3-butylene glycol, or a mixed solution thereof is particularly preferably used for extracting the extract. Since these have few side effects on the human body and are substances that can be separately added to the external preparation for skin according to the present invention, they can be used as they are without completely removing the solvent in the extraction process of the extract.

  In order to suitably extract an active ingredient having an anti-itching effect from the active ingredient, when ethanol is used as the solvent, a 10-90% aqueous solution is preferably used, and a 30-70% aqueous solution is more preferably used. For the same reason, when 1,3-butylene glycol is used, a 10-90% aqueous solution is preferably used, and a 30-70% aqueous solution is more preferably used. Further, the solvent is preferably 1.5 to 5 times the weight of the original material or more. If the solvent weight is less than 1.5 times, it is difficult to completely extract the extract from the active ingredient, and if it exceeds 5 times, it takes a long time to remove the solvent later.

  The method of extracting the extract from the active ingredient is not particularly limited, and it is appropriately selected from a method in which the active ingredient is immersed in a solvent at room temperature or under heating, a method of heating and refluxing, a method of stirring with a stirrer and the like. You can choose. The extract after the extraction is then purified by appropriately selecting steps such as filtration and separation of impurities, liquid-liquid extraction with an anhydrous solvent, decolorization, and deodorization. Moreover, when removing a solvent from the extract after refinement | purification, although vacuum pressure reduction is common, it is not limited to this.

  The content of the extract of the spinach in the external preparation for skin is 0.1 to 50% by weight, preferably 1 to 20% by weight, based on the total weight of the external preparation for skin when converted to the dry weight of the extract. Preferably, it is 5 to 15% by weight. When the content does not reach 0.1% by weight, the content of the medicinal component is not sufficient, and a high anti-stagnation effect cannot be expected. Moreover, when it exceeds 50 weight%, a medicinal component becomes excess and the effect commensurate with an increase cannot be acquired.

  The above-mentioned content represents a preferred concentration of extract of the extract of the spinach when the external preparation for skin according to the present invention is applied to the affected area, and is concentrated or changed by changing the content of the base or the like. This is not the case when the external preparation for skin is distributed or supplied in a diluted state.

Next, camellia oil, which is an essential component for the external preparation for skin according to the present invention, will be described.
Camellia oil is a fatty oil obtained from the seeds of plants belonging to the Camellia family, and in particular, a fatty oil obtained from seeds excluding the seed coats of plants belonging to the Camellia family (Theaceae). Typical examples include Camellia japonica, Camellia reticulata, and Camellia sasanqua.

  Camellia oil is non-drying and stable against oxidation and generally contains 79 to 85% or more oleic acid (unit price unsaturated fatty acid) and 2 to 9% linoleic acid (polyunsaturated fatty acid). It is a feature. Specifically, for example, a camellia camellia oil contains about 85% oleic acid and about 4% linoleic acid, and a sasanqua camellia oil contains about 80% oleic acid and about 8% linoleic acid. It is common. In addition, the content of palmitic acid (saturated fatty acid), which is another component, is about 8% for camellia camellia oil and about 9% for southern camellia oil. It can be said that is harder to solidify.

  As the camellia oil used for maintaining the pharmacological effect of the extract of spinach longer and achieving the object of the present invention, it is not particularly limited among the above, but from the viewpoint of permeability to the skin and oxidation resistance Therefore, a camellia camellia oil having a high oleic acid content is particularly preferably used.

  Methods for obtaining camellia oil from camellia plants include crushing dried seeds, steaming and squeezing them with a mortar, or extracting them by dissolving the oil with a solvent and fractionating with a difference in boiling points, etc. Although there are a plurality, camellia oil used as a component of the external preparation for skin according to the present invention is not limited to any one, and can be arbitrarily selected and employed.

The content of camellia oil is 0.1% by weight or more, and the content of camellia oil is 0.1 to 10% by weight, more preferably 1 to 5% by weight, based on the total weight of the external preparation for skin. . Preferably, if the content of camellia oil does not reach 0.1% by weight, the effect of extending the medicinal sustainability of the spinach extract is not sufficiently obtained. The upper limit varies depending on the form of the external preparation for skin. For example, in the case of gel or cream, there is a problem that even if it exceeds 10% by weight, the effect corresponding to the increase is not obtained and the gel is broken. Moreover, it is preferable that a camellia oil is the ratio of 0.05 to 0.5 time by weight ratio with respect to the extract of spinach.

  The content of the camellia oil represents the preferred concentration of camellia oil when the external preparation for skin according to the present invention is applied to the affected area, and is concentrated by changing the blending ratio of the base and the like. Alternatively, when the external preparation for skin is distributed or supplied in a diluted state, this is not the same as in the case of the above-mentioned spinach extract.

  As other components to be blended in the external preparation for skin according to the present invention, the effects of the above-described extract of the spinach and camellia oil are not impaired, and as an ingredient generally used for constituting the external preparation for skin, an aqueous or oily base is used. Agents, various plant extracts, moisturizers, anti-inflammatory agents, purified water, thickeners, emulsifiers, gelling agents, emollients, pH regulators, preservatives, surfactants, UV absorbers, UV scattering agents, antioxidants , Fragrances, colorants and the like can be blended.

  Among these, for plant extracts, lemon, arnica, linden, scallop, carrot, rosemary, aloe, loofah, sasa, green tea, comfrey, button, mulberry, oxon, horsetail, hypericum, pine, peach, rose, loquat, seaweed The extract can be used by appropriately selecting from the kind. For example, a lemon is a fruit, an arnica is a flower and a leaf, a linden is a flower, a peach tree is a leaf, a carrot is a root, a rosemary is a flower and a leaf, an aloe is a leaf, a loofah is a ground part, and a sasa is Leaf, Green tea leaves, Comfrey leaves, Buttons peels, Mulberry rhizomes, Horsetails roots, Horsetails whole plants, Hypericum flowers, Pines fruits and leaves, Peach leaves Preferably, roses use flowers and loquats use leaves.

  The method for extracting the extract from these plants is not particularly limited, and can be appropriately selected from the extraction methods and solvents related to the extract of spinach. Moreover, when extracting an extract from these plants, it does not prevent performing the extraction work of a spinach extract simultaneously using a common solvent.

Hereinafter, the skin external preparation according to the present invention will be described more specifically with reference to Examples. However, the present invention is not limited to the following examples.
First, the spinach extract and camellia oil, which are essential components of the external preparation of the present invention, were obtained as follows.

(About extract of spinach extract)
15 kg of the whole botanical grass (but only the above-ground part) that had been sufficiently shade-dried and finely cut was immersed in 30 L of 35% ethanol aqueous solution and leached at room temperature for 2 weeks. In addition, it stirred 2 to 3 times a day. This was filtered to obtain an extract, and then concentrated by vacuum decompression and further dried to obtain 120 g of powdered spinach extract. This extraction operation was repeated according to the weight of the external preparation for skin necessary for the test.

(About camellia oil)
The cocoon oil made by Oshima Kaoru was used. This camellia oil is Camellia japonica-based camellia oil having a saponification number of 189.1, an oleic acid content of 79.5%, a linoleic acid content of 8.0%, and a palmitic acid content of 8.8%. .

Example 1
In addition to the above essential components, the components shown in Table 1 below were mixed in the blending amounts (% by weight) shown in Table 1 to prepare prototype gel 1. Table 7 shows the use conditions for evaluating the quality of the prototype gel 1, and Table 8 shows the answers to the questionnaire on the use results.

(Example 2)
In addition to the above essential components, the components shown in Table 2 below were mixed in the blending amounts (% by weight) shown in Table 1 to obtain prototype gel 2. Table 7 shows the usage conditions, and Table 8 shows the answers to the questionnaire on the usage results.

(Example 3)
In addition to the above essential constituents, the components shown in Table 3 below were mixed in the blending amounts (% by weight) shown in Table 1 to obtain prototype gel 3. Table 7 shows the usage conditions, and Table 8 shows the answers to the questionnaire on the usage results.

Example 4
In addition to the above essential components, the components shown in Table 4 below were mixed in the blending amounts (% by weight) shown in the same table to obtain prototype cream 1. Table 7 shows the usage conditions, and Table 8 shows the answers to the questionnaire on the usage results.

(Comparative Example 1)
Only the spinach extract was blended in zero, and the components shown in Table 5 below were mixed in the blending amounts (% by weight) shown in the same table to obtain a comparative product gel a. Table 7 shows the usage conditions, and Table 8 shows the answers to the questionnaire on the usage results.

(Comparative Example 2)
Only camellia oil was blended in an amount of zero, and the components shown in Table 6 below were mixed in the blending amounts (wt%) shown in the table to obtain a comparative product cream a. Table 7 shows the usage conditions, and Table 8 shows the answers to the questionnaire on the usage results.

(Evaluation methods)
The above-mentioned prototype gels 1 to 3, trial creams 1 to 3, comparative gels and creams are composed of a wide range of ages from 18 to 68 years including 4 years old infants, all of which are allergic to chronic allergies The use test was conducted by male and female subjects with symptoms (total of 6 men and women in each group). After each subject repeatedly used two types of external preparations alternately, a questionnaire regarding the comparison of efficacy was conducted. The details of the use conditions are shown in Table 7 below, and the results of questionnaire responses after the use test are shown in Table 8 below.

  The following is added to the results of the usage test. First of all, compared to Group 1, which compares Prototype Gel 1 (Example 1) and Prototype Gel 2 (Example 2), the effect of improving stagnation is clearly better for Gel 2, and the sustained efficacy is greater than this result. I found no difference. This is considered to be due to an increase in the blending amount of the spinach extract from 5.0% to 10.0%. There is no big difference in the response regarding the duration of the pharmacological effect, but this shows that the amount of camellia oil is about 2%, and the effect is sufficient. It is thought that it shows.

  From group 2, which compared prototype gel 1 (Example 1) and prototype gel 3 (Example 3), although it was found that gel 3 was slightly effective in improving itchiness, the same number of results were obtained for sustained drug efficacy. It was. The reason is that the blending amounts of the spinach extract and camellia oil are 5.0% and 2.0%, respectively. In addition, gel 3 was slightly better in terms of itch improvement, but this was presumably due to the effects of plant extracts other than spinach (Arnica extract, lemon extract, carrot extract, Chinese mugwort extract, linden extract, rosemary water). Is done. However, it is clear from this result and the following group 3 test results that the degree of pharmacological effect is not as good as that of the spinach extract.

  From the group 3 which compared the prototype gel 1 (Example 1) and the comparison target gel a (Comparative Example 1), the result that Gel 1 is overwhelmingly good in both the stagnation improvement effect and the medicinal sustainability was obtained. . Compared with the results of Group 2 in which the superiority and inferiority of the effects of Gel 1 and Gel 3 (Example 3) are antagonized, the gel a with the amount of the spinach extract blended to zero and the weight distributed to other plant extracts is the effect of improving itchiness. Is clearly inferior, and it is clear that this represents a difference in superiority or inferiority of the pharmacological effects between the spinach extract and other plant extracts.

  From the test results so far, gels 1 to 3 (Examples 1 to 3) show the effect of the present invention in both the stagnation-improving effect and the sustained efficacy, whereas gel a (Comparative Example 1) shows the effect. It was found that the pharmacological effect of the spinach extract and the blending amount increased within a predetermined range, and the effect of improving itchiness is enhanced.

From group 4 which compared cream 1 (Example 4) and cream a (Comparative Example 2), the amount of camellia oil blended to zero and the weight assigned to squalene cream a contains 2.0% camellia oil. As a result, the medicinal sustainability was inferior to that of Cream 1 to be performed. The itch improvement effect was the same. In addition, since both cream 1 and cream a contain a surfactant, no significant difference is shown in the effect of improving itchiness and sustaining medicinal effect. Note that both squalene and camellia oil, both of which are derived from natural products and are known to have a moisturizing effect on the skin, the latter has a superior effect of extending the duration of the pharmacological effect.
Moreover, in the comparative test by the group 5 of the gel 3 (Example 3) and the cream 1 (Example 4), the result that the gel was excellent was obtained.

  From the results of the above-mentioned use test, camellia oil has an excellent effect of extending the duration of the pharmacological effect, and by increasing the amount of camellia oil within a predetermined range, the medicinal sustainability is further extended. I found out that I can do it.

  From the use test by the above Examples and Comparative Examples, it can be said that the external preparation for skin according to the present invention can suitably obtain both the effect of improving itchiness by the extract of spinach extract and the effect of extending the medicinal durability by camellia oil.

  The present invention provides an external preparation for skin that suppresses itching caused by allergic dermatitis and the like and has a sustained pharmacological effect. However, the external preparation for skin according to the present invention provides skin inflammation, It is also effective against dryness, roughness, cracks, cracks and dandruff. In addition, the effect of extending the duration of the pharmacological effect of camellia oil is remarkable when used in combination with the extract of spinach, so that it is possible to provide a skin external preparation with a high pharmacological effect and excellent pharmacological effect. There are significant contributions in the manufacturing and therapeutic fields.

Claims (4)

An external preparation for skin comprising an extract of spinach and camellia oil. The skin external preparation according to claim 1, wherein the camellia oil is Camellia japonica L. camellia oil. The content of the extract of the spinach is 1 to 20% by weight with respect to the external preparation for skin, and the content of camellia oil is 1% by weight or more with respect to the external preparation for skin. The skin external preparation as described. The skin external preparation according to any one of claims 1 to 3, wherein the amount of the camellia oil is 0.05 to 0.5 times the weight ratio of the extract of the spinach.