JP2007145793A - External preparation for promoting blood circulation, and cosmetic for skin and hair, and bathing agent containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation for promoting blood circulation, having excellent solubility and percutaneous absorption, hardly causing irritation and applicable to the whole body. <P>SOLUTION: The external preparation for promoting the blood circulation comprises a fatty acid ester represented by general formula (1) [wherein, R1 is a 5-10C alkyl group or a 5-10C alkenyl group both may have substituents, (with the proviso that an octyl group which does not have a substituent is excluded)]. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a blood circulation promoting external preparation, a cosmetic and a bath containing the same. More specifically, the present invention relates to a blood circulation promoting external preparation which is excellent in solubility and transdermal absorbability and can be applied to the whole body, and a skin / hair cosmetic and a bath preparation containing the same.

In recent years, with the spread of word processors and personal computers, the number of people who spend the same posture for a long time in the office has increased, thereby preventing microcirculation or local circulation and causing poor blood circulation such as swelling of the legs. Seasonal changes also change life activities. In winter, for example, poor circulation such as peripheral circulation causes skin troubles such as moistness and rough skin. Furthermore, various obstacles resulting from poor blood circulation are also brought about by a decrease in physical function due to aging, tension from stress and lack of sleep.
Swelling of the feet due to these blood circulation disorders, swollen eyelids, dull eyes and complexion are serious problems from a cosmetic point of view. Has been proposed.

  For example, a technique for improving swelling with a cosmetic containing a lipolytic agent such as gentian pepper extract (Patent Document 1), a technique for improving swelling with a lipolytic agent such as caffeine, jujuy extract, and fennel (Patent Document 2). Is mentioned. However, the swell targeted by these techniques is considered to indicate sag due to excessive accumulation of subcutaneous fat, unlike the swell due to poor blood circulation described above. Moreover, application to parts other than the face is not mentioned. In addition, these herbal ingredients have their own odors, and therefore have a drawback in that it is difficult to add an amount sufficient to exert an effect when blended into a cosmetic amount.

  On the other hand, capsaicin and various analogs thereof such as chili powder, chili tincture, chili extract, capsaicin, homocapsaicin, homodihydrocapsaicin, nonanoic acid vanillylamide are known as substances that give warm feeling during use and improve blood flow. ing. However, these blood flow improving agents represented by capsaicin and the like exhibit strong irritation and heat sensitivity that are painful to the skin even in a small amount. In addition, in order to alleviate these irritation properties, even when trying to be blended into various products in a state dissolved in an oily base material, it dissolves in alcohol but is extremely low in solubility in oily base materials commonly used in cosmetics, and crystals are precipitated. Therefore, it is difficult to obtain a stable blood flow improvement effect while relaxing the irritation by dissolving and diluting to an appropriate concentration locally. In order to solve such problems, synthesis of vanillyl alcohol alkyl ether derivatives such as vanillyl propyl ether, vanillyl butyl ether, vanillyl pentyl ether, and vanillyl hexyl ether (Patent Document 3) has also been studied. Although the sex has been improved, irritation and heat sensitivity to the skin are still strong, and a satisfactory blood circulation promoting external preparation applicable to the whole body has not yet been obtained.

  As mentioned above, it is well known that capsaicins (capsaicin, dihydrocapsaicin, etc., hereinafter simply referred to as “capsaicinoid”), which are the main components of chili, have a blood circulation promoting action, and some of the heat Although it is actually used in formulations such as ships and creams, capsaicins are problematic in terms of skin irritation, invasive action, or their poor solubility, and there are limits to their formulation in cosmetics (non-patented) Reference 1) has also been tried to improve solubility and irritation by using vanillyl alcohol alkyl ether derivatives, etc., but the effect is not sufficient, it has excellent solubility and transdermal absorbability, and irritation. The actual situation is that a blood circulation promoting external preparation applicable to the whole body, a skin / hair cosmetic and a bath preparation containing the same are not yet obtained.

JP 2001-199896 A JP 2000-119157 A JP 57-9729 A Pain (1999), 81 (1, 2), 135-145

  Therefore, an object of the present invention is to obtain a blood circulation promoting external preparation which is excellent in solubility and transdermal absorbability and which can be applied to the whole body and which can be applied to the whole body, and skin and hair cosmetics and bath preparations containing the same. It is in.

The present inventors have various physiological activities and capsinoid compounds (fatty acid esters of vanillyl alcohol, capsiate, which is a fatty acid ester that does not exhibit a pungent taste and has been studied for application to functional foods and pharmaceuticals by oral ingestion [ 4-hydoxy-3-methoxybenzyl (E) -8-methyl-6-nonenoate], dihydrocapsiate [4-hydroxy-3-methoxybenzyl 8-methylnonanoate], etc., see JP-A-11-246478 (hereinafter simply referred to as “capsinoid”). ) And focusing on the action when applied to the skin, surprisingly, the fatty acid ester is highly soluble in various cosmetic oil bases and transdermally. It has been found that it has excellent absorbability, and has almost no irritation and heat sensitivity even when applied to the skin, and has a blood circulation promoting effect applicable to the whole body.
That is, the present invention provides a blood circulation promoting external preparation applicable to the whole body using a fatty acid ester, a skin / hair cosmetic and a bath containing the same.
Conventionally, capsinoid, a kind of fatty acid ester, has been found to be present in other plants belonging to the genus Capsicum (Garden Society 58, 601-607) and confirmed to be an edible natural compound. ing. Such capsinoids are reported to have specific physiological activity such as immune activation, energy metabolism activation, obesity suppression, etc., without showing pungency, despite being a structural analogue of capsaicinoid. However, there is a report that it has no effect on the application to the skin, and it has not been examined in detail (Non-patent literature: Neuropharmacology (2003), 44 (7), 958-967). Therefore, the effects of the percutaneous absorption as a blood circulation promoting external preparation were first found by the present inventors.

（上記一般式（１）において、Ｒ１は、炭素数５から１０のアルキル基又は炭素数５から１０のアルケニル基を示し、置換基を有していてもよい。（ただし置換基を有しないオクチル基を除く））
（３）上記一般式（１）において、R１が、ヘキシル基、ヘプチル基、６−メチルヘプチル基、５−メチルヘプチル基、７−メチルオクチル基、６−メチルオクチル基、トランス−７−メチル−５−オクテニル基、ノニル基、８−メチルノニル基、７−メチルノニル基及びデシル基からなる群より選ばれる基である、（１）又は（２）のいずれか記載の血行促進外用剤。
（４）脂肪酸エステルがカプシエイト、ジヒドロカプシエイト、ノルジヒドロカプシエイト、バニリルデカノエイト、バニリルオクタノエイト、バニリルウンデカノエイト、バニリル９−メチルデカノエイト、バニリル６−メチルオクタノエイト、バニリル７−メチルノナノエイト、バニリル８−メチルデカノエイト及びこれらの混合物からなる群より選ばれるものである、（１）乃至（３）のいずれか記載の血行促進外用剤。
（５）（１）乃至（４）のいずれか記載の血行促進外用剤を含有してなる皮膚・毛髪用化粧料及び入浴剤。
（６）バニリルウンデカノエイト、バニリル９−メチルデカノエイト、バニリル６−メチルオクタノエイト、バニリル７−メチルノナノエイト、バニリル８−メチルデカノエイトから選択されるいずれかの化合物。 That is, the present invention includes at least the following contents.
(1) An external agent for promoting blood circulation, comprising a capsinoid compound.
(2) The blood circulation promoting external preparation according to (1), wherein the capsinoid compound is selected from compounds represented by the following general formula (1).

(In the general formula (1), R1 represents an alkyl group having 5 to 10 carbon atoms or an alkenyl group having 5 to 10 carbon atoms, and may have a substituent. (However, octyl having no substituent) Except group))
(3) In the above general formula (1), R1 is a hexyl group, heptyl group, 6-methylheptyl group, 5-methylheptyl group, 7-methyloctyl group, 6-methyloctyl group, trans-7-methyl- The blood circulation promoting external preparation according to any one of (1) and (2), which is a group selected from the group consisting of a 5-octenyl group, a nonyl group, an 8-methylnonyl group, a 7-methylnonyl group, and a decyl group.
(4) Fatty acid ester is capsiate, dihydrocapsiate, nordihydrocapsiate, vanillyl decanoate, vanillyl octanoate, vanillyl undecanoate, vanillyl 9-methyldecanoate, vanillyl 6-methyloctanoate, vanillyl The blood circulation promoting external preparation according to any one of (1) to (3), which is selected from the group consisting of 7-methylnonanoate, vanillyl 8-methyldecanoate, and a mixture thereof.
(5) A cosmetic for skin / hair and a bath containing the blood circulation promoting external preparation according to any one of (1) to (4).
(6) Any compound selected from vanillyl undecanoate, vanillyl 9-methyldecanoate, vanillyl 6-methyloctanoate, vanillyl 7-methylnonanoate, vanillyl 8-methyldecanoate.

  ADVANTAGE OF THE INVENTION By this invention, the blood circulation promotion external preparation which is excellent in solubility and transdermal absorbability, and can be applied to the whole body with little irritation is provided. In addition, by using skin / hair cosmetics and bath preparations containing this, there is less irritation and a high blood flow improvement effect. As a result, such as eyelid swelling, darkness, darkening of the complexion, etc. It is possible to provide cosmetics effective for improvement, hair cosmetics for promoting hair growth and hair growth, and bathing agents having a high fatigue recovery effect by improving blood flow throughout the body.

  By using the above-mentioned external preparation for promoting blood circulation according to the present invention, a cosmetic for skin and hair and a bath preparation excellent in improving effects such as swelling of the foot due to blood circulation disorder, swollen eyelids, dark eyes and complexion of complexion. Can be provided. Specific examples of the present invention will be described below.

（上記一般式（１）においてＲ１は、炭素数５〜１０のアルキル基又は炭素数５から１０のアルケニル基を示し、置換基を有していてもよい。（ただし置換基を有しないオクチル基を除く）） The capsinoid compound used as an active ingredient of the external agent for promoting blood circulation of the present invention refers to a vanillyl alcohol fatty acid ester, and representative examples thereof include capsiate and dihydrocapsiate, which have been confirmed as components contained in red peppers. , Nordihydrocapsiate, and various linear fatty acids such as vanillyl decanoate (4-hydroxy-3-methoxybenzyl decanoate (caprate)) and vanillyl octanoate [4-hydroxy-3-methoxybenzyl octanoate]. And fatty acid esters of vanillyl alcohol.
Therefore, the capsinoid compound can also be expressed as in the following general formula (1).

(In the general formula (1), R1 represents an alkyl group having 5 to 10 carbon atoms or an alkenyl group having 5 to 10 carbon atoms, and may have a substituent. (However, an octyl group having no substituent) except for))

  Here, the alkyl group having 5 to 10 carbon atoms represented by R1 may be linear or branched. For example, n-pentyl group, sec-pentyl group, tert-pentyl group, isopentyl group N-hexyl group, isohexyl group, heptyl group, nonyl group, decyl group, undecyl group and the like, and other various branched isomers. Since it is confirmed to exist in natural pepper, it is preferably a branched chain.

  The alkenyl group having 5 to 10 carbon atoms represented by R1 may be linear or branched, and the number of double bonds may be one or two, for example, Examples include a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, a nonenyl group, a decenyl group, an undecenyl group, and the like, and other various branched chain isomers. The double bond site may be either trans or cis, but is preferably trans.

  These groups may be optionally substituted with 1 to 4 substituents, and examples of the substituent include an alkyl group, a halogen atom, a haloalkyl group, an amino group, a hydroxyl group, an acyl group, a nitro group, a cyano group, Examples include thiol groups. Especially, the thing substituted by the C1-C4 short chain alkyl group is preferable. Examples of the alkyl having 1 to 4 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, t-butyl group, and isobutyl group. Among these substituents, a methyl group or an ethyl group is particularly preferable, and it is preferable that a hydrogen atom on the carbon atom at the 2nd or 3rd position as counted from the terminal methyl side is substituted.

  R1 is preferably a hexyl group, heptyl group, 6-methylheptyl group, 5-methylheptyl group, 7-methyloctyl group, 6-methyloctyl group, trans-7-methyl-5-octenyl group, nonyl group, Examples include an 8-methylnonyl group, a 7-methylnonyl group, and a decyl group.

  Of these, vanylyl undecanoate, vanillyl 9-methyldecanoate, wherein R1 is decyl group, 8-methylnonyl group, 5-methylheptyl group, 6-methyloctyl group and 7-methylnonyl group, Vanillyl 6-methyloctanoate, vanillyl 7-methylnonanoate and vanillyl 8-methyldecanoate are novel compounds synthesized for the first time by the present inventors. Accordingly, the present invention includes inventions relating to these compounds.

Among them, capsiate, dihydrocapsiate, nordihydrocapsiate are preferable because they are contained in spicy pepper as a component in a large amount. These compounds have the following structural formula:

  In addition, since it has the same activity as capsiate, vanillyl decanoate, vanillyl octanoate, vanillyl undecanoate, vanillyl 9-methyldecanoate, vanillyl 6-methyloctanoate, vanillyl 7- Methyl nonanoate, vanillyl 8-methyldecanoate, and the like are also preferable.

  Since the capsinoid compounds described above are contained in a large amount in plants belonging to the genus Capsicum, extraction, separation and purification from the plants and / or fruits of the plant belonging to the genus Capsicum (hereinafter referred to as “capsicum”). Can be prepared. Capsicum used for extraction may be derived from capsicin varieties having a strong pungent taste typified by `` Nikko '', `` Five colors '', etc., but those containing strong capsaicin are not preferred, `` CH-19 sweet '', It is preferable to use the conventional spicy varieties of chili peppers that contain a large amount of capsinoids such as “Manganji”, “Fushimi Amanaga”, shiso, green pepper and the like. Among them, “CH-19 sweet” which is a spicy varieties has a high content of the component and is particularly preferable as an extraction raw material. Here, the term “CH-19 sweet” includes “CH-19 sweet” and progeny related varieties derived from “CH-19 sweet”. In this specification, “CH-19 sweet” Is used to mean all of these. Extraction / separation / purification can be carried out by solvent extraction well known to those skilled in the art, various types of chromatography such as silica gel chromatography, high-performance liquid chromatography for preparation, etc. alone or in combination as appropriate, For example, the method described in JP-A-11-246478 can be used.

  The capsinoid compound described above can also be synthesized by a transesterification reaction using a corresponding fatty acid ester and vanillyl alcohol as starting materials based on, for example, JP-A No. 11-246478. Alternatively, it may be synthesized by other reaction methods well known to those skilled in the art based on the structural formula. Furthermore, a capsinoid compound can also be easily prepared by a synthetic method using an enzyme. For example, by utilizing the reverse reaction of lipase using a fatty acid ester corresponding to a desired compound and / or a compound such as triglyceride having the fatty acid and vanillyl alcohol as a substrate by the method described in JP-A-2000-312598 Thus, a desired fatty acid ester can be obtained.

  Capsinoids have a structure in which the amide bond of capsaicin is replaced with an ester bond, and thereby various characteristic differences different from capsaicin are expressed. That is, when administered orally or dermally to the human body, there is very little pungency or irritation compared to capsaicin, and conversely, the solubility in various organic solvents is remarkably increased. It becomes possible to improve applicability and transdermal absorbability. Such characteristics of capsinoids, when used as a blood circulation promoting external preparation, in skin and hair cosmetics, bathing agents, etc., demonstrate ease of formulation design and formulation, good usability, or intended blood flow improvement effect This is a particularly effective characteristic.

Conventionally used blood circulation promoters may be used in combination with the blood circulation promoter of the present invention. Examples of such blood circulation promoters include chili powder, chili tincture, chili extract, capsaicin, homocapsaicin, homodihydrocapsaicin. , Nonanoic acid vanillyl amide, capsaicin, ginger extract, red pepper extract, nicotinic acid, cucumber extract, ogi extract, citrus extract, koji extract, salamander extract, tangin extract, chixetsunjin extract, Ginseng extract, γ-aminobutyric acid (GABA), and the like.
Furthermore, various components that are generally used as cosmetics or external preparations for skin can be added to the blood circulation promoter of the present invention as long as the effects of the present invention are not impaired. Such components include oily substrates, surfactants, polymer substances, solvents, powder substances, antioxidants, anti-inflammatory agents, UV absorbers, whitening agents, cell activators, moisturizers, metal chelating agent dyes , Fragrances, transdermal absorption promoters and the like.

  Examples of the oily base material include hydrocarbons such as squalane, liquid paraffin, light liquid isoparaffin, heavy liquid isoparaffin, microcrystalline wax, solid paraffin, dimethicone, femethicone, cyclomethicone, amodimethicone, and polyether-modified silicone. Silicones, jojoba oil, carnauba wax, owl, beeswax, geiwa, octyldodecyl oleate, isopropyl myristate, esters such as neopentyl glycol diisostearate, diisostearate malate, stearic acid, lauric acid, Fatty acids such as myristic acid, palmitic acid, isostearic acid, isopalmitic acid, behenic acid, oleic acid, acyl glutamic acid, acyl glycine, acyl alanine, acyl sarcosine Acylamino acids, higher alcohols such as behenyl alcohol, cetanol, oleyl alcohol, octadecyl alcohol, castor oil, coconut oil, hydrogenated coconut oil, coconut oil, wheat germ oil, isostearic acid triglyceride, isooctanoic acid triglyceride, olive oil and other triglycerides And the like.

  Examples of the surfactant include sorbitan sesquioleate, sorbitan monooleate, sorbitan trioleate, sorbitan sesquistearate, sorbitan monostearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene stearate. , Polyoxyethylene oleate, polyoxyethylene glyceryl fatty acid ester, polyoxyethylene alkyl ether, nonionic surfactant such as polyoxyethylene hydrogenated castor oil, sodium lauryl stearate, polyoxyethylene alkyl sulfate, sulfosuccinate , Anionic surfactants such as acyl glutamate, acyl sarcosine, acyl glycine, and acyl alanine, and quaternary alkyl ammonium salts. On surfactants, amphoteric surfactants such as alkylbetaines, emulsifier include solubilizing agents, and the like.

  Examples of the solvent include lower alcohols such as ethanol, polyhydric alcohols such as 1,2-pentanediol, 1,2-hexylene glycol and isoprene glycol, ethers and other organic solvents, water, and the like. it can.

  Examples of the polymer substance include polyamino acids such as polyaspartic acid, ε-polylysine, γ-polyglutamic acid and derivatives thereof, natural polymer compounds such as collagen and elastin, and semisynthetic polymer compounds such as partially deacetylated chitin. And synthetic polymer compounds such as carboxymethylcellulose.

  Examples of the powder substance include organic powders such as crystalline cellulose, cross-linked methylpolysiloxane, polyethylene powder, acrylic resin powder, talc, mica, sericite, magnesium carbonate, calcium carbonate, titanium dioxide, iron oxide, and bitumen. Powders that may be surface treated such as ultramarine, titanium mica, titanium sericite, silica, etc., fine particle composite powder (hybrid fine powder), pearlescent pigments such as titanium dioxide coated mica, photochromic pigment, nylon powder And polymer powders such as N-ε-lauroyllysine.

  Examples of the dyes include legal tar dye first class, legal tar dye second class, legal tar dye third class, hair dye, natural dye, mineral dye, and the like.

  Examples of the fragrances include animal fragrances such as musk, plant fragrances such as jasmine oil, synthetic fragrances such as α-amylcinnamaldehyde, and blended fragrances.

  Examples of the transdermal absorption enhancer include urea, 2-pyrrolidone, 1-hexanol, 1-octanol, 1-decanol, 1-menthol, sodium lauryl sulfate, isopropyl myristate, n-hexyl acetate, oleic acid and the like. be able to.

  The external preparation for improving blood flow of the present invention can be used as a cosmetic for skin and hair, a bath agent, or a toiletry product by blending various other components as described above according to a conventional method, if necessary. There is no restriction | limiting in particular, Arbitrary dosage forms, such as solution form, paste form, gel form, solid form, and powder form, can be taken. For example, oil, lotion, cream, emulsion, gel, shampoo, hair rinse, hair conditioner, enamel, foundation, lipstick, funny, pack, ointment, granule, capsule, perfume, powder, cologne, toothpaste, soap , Aerosol, cleansing foam and the like. Furthermore, the external preparation for improving blood flow of the present invention is a pharmaceutical used for the prevention or improvement of various skin diseases such as a hair nourishing agent, an agent for improving skin aging prevention, a skin cosmetic solution, an agent for preventing and improving rough skin caused by chilli and cracks, and the like. It can also be used for quasi-drugs.

(Example)
The present invention will be described more specifically with reference to examples (and formulation examples), but the present invention is not limited to these examples. In these examples, the blending amount was expressed as wt%.

  The solubility of capsaicin at room temperature was compared with capsinoids for various oils (mixed products prepared by the method described in Reference Example (5) were used. The same applies hereinafter). As is clear from Table-1, capsaicin was not dissolved in various cosmetic oils, but crystals were precipitated, whereas capsinoid was originally a liquid at room temperature at room temperature, and prescribed amounts were added to various oils. It was confirmed that it was quickly and uniformly dissolved. From these results, it was found that capsinoids are easier to uniformly emulsify and disperse than capsaicin when blending cosmetics such as creams and emulsions, and are easy to adjust the concentration and manufacture.

Capsaiin (a mixture prepared by the method described in Reference Example (5) was used. The same applies hereinafter) and capsaicin were compared for vasodilator effects using hairless mouse auricles.
[Test Method] A sample was applied to the right ear of a hairless mouse (HR-1, female) and a control was applied to the left ear, and the presence or absence of erythema was visually evaluated.
Sample: (1) Capsinoid (1wt% and 5wt% dissolved in liquid paraffin)
(2) Capsaicin (1wt% and 5wt% dispersed in liquid paraffin)
Control: Liquid paraffin
[Results] As a result of visual determination, erythema was observed with capsaicin at 1 wt%, whereas erythema did not occur with capsinoid, and with 5 wt%, both capsaicin and capsinoid had clear auricles after 30 minutes from application. Erythema was confirmed. The erythema that developed disappeared completely after about 2 hours with capsinoids, whereas the erythema maintained its initial state after 2 hours even with the application of 1% by weight of capsaicin. On the other hand, no erythema was observed in the control liquid paraffin coating. Note that, as seen in the results of Example 1, capsaicin was not completely dissolved in liquid paraffin, and both 1 wt% and 5 wt% were evaluated in a dispersed state.
From these results, it was found that capsaicin has a strong blood circulation promoting action and long persistence, whereas capsinoid has moderate persistence and strength, and is a suitable blood circulation promoter for cosmetic use.

The vasodilatory effect and irritation of capsinoid (mixed product prepared by the method described in Reference Example (5), hereinafter the same) was evaluated using the human facial cheek.
[Test method]
Application site: Facial cheeks (per side of nose)
Sample: 30 wt% capsinoid (in isopropyl alcohol)
Control: Isopropyl alcohol volunteer: 5 males Test procedure: Based on the following procedure. Samples were prepared with a double blind, and the order of application and site (right cheek or left cheek) were also randomly performed.
(1) Remove the oil on the application site with ethanol before evaluation (2) Apply the sample to the right cheek (or left cheek) (use a cotton swab)
(3) Apply control to cheek opposite to (2) (use cotton swab)
(4) The following evaluation items are evaluated:
(A) The evaluator visually compares the degree of erythema with the control part and determines (b) The subject compares the intensity of the irritant feeling with the control part and answers [Result] The part where the sample is applied for both irritation and erythema Was confirmed.
About irritation:
There is no sense of irritation, but there is a sense of incongruity 3 people I feel a sense of irritation 1 person I feel a sense of irritation About 1 person
3 people with slight erythema 2 people with clear erythema

Despite being applied at a high concentration of 30 wt%, over half of the people felt a slight irritation and discomfort, and the sensation disappeared within 2 hours. On the other hand, with regard to erythema, an effect was observed in most subjects, and it was also confirmed in a test using a human face that capsinoid has a blood flow improving effect without giving a sense of irritation.

In the same manner as in Example 2, the vasodilatory effects of various capsinoid compounds prepared according to the method described in Reference Example were compared using hairless mouse auricles. All samples were dissolved in liquid paraffin.
Sample: (1) Vanillyl alcohol (5 wt% dissolved in liquid paraffin)
(2) Capsaicin (1wt% and 5wt% dissolved in liquid paraffin)
(3) Capsiate (1wt% and 5wt% dissolved in liquid paraffin)
(4) Dihydrocapsiate (1wt% and 5wt% dissolved in liquid paraffin)
(5) Nordihydrocapsiate (1wt% and 5wt% dissolved in liquid paraffin)
(6) Vanillyl octanoate (1wt% and 5wt% dissolved in liquid paraffin)
(7) Vanillyl decanoate (1wt% and 5wt% dissolved in liquid paraffin)
(8) Vanillyl undecanoate (1wt% and 5wt% dissolved in liquid paraffin)
(9) Vanillildo decanoate (1wt% and 5wt% dissolved in liquid paraffin)
(10) Vanillyl tridecanoate (1wt% and 5wt% dissolved in liquid paraffin)
(11) Vanillyl pentadecanoate (1wt% and 5wt% dissolved in liquid paraffin)
(12) Vanillyl octadecanoate (1wt% and 5wt% dissolved in liquid paraffin)
(13) Vanillyl oleate (1wt% and 5wt% dissolved in liquid paraffin)
(14) Vanillyl linoleate (1wt% and 5wt% dissolved in liquid paraffin)
(15) Vanillyl 9-methyldecanoate (1wt% and 5wt% dissolved in liquid paraffin)
(16) Vanillyl 6-methyloctanoate (1wt% and 5wt% dissolved in liquid paraffin)
(17) Vanillyl 7-methylnonanoate (1wt% and 5wt% dissolved in liquid paraffin)
(18) Vanillyl 8-methyldecanoate (1wt% and 5wt% dissolved in liquid paraffin)
Control: Liquid paraffin results are shown in Table 2. As a result, an effect of promoting blood circulation by external application was confirmed for a capsinoid compound having a side chain fatty acid having 11 or less carbon atoms. Moreover, it was confirmed that the capsinoid compound shows the same effect even if it is a mixture or a single component. Of these, vanillyl undecanoate, vanillyl 9-methyl decanoate, vanillyl 6-methyl octanoate, vanillyl 7-methyl nonanoate, vanillyl 8-methyl decano newly synthesized by the present inventors. The activity was also confirmed for Eight.

[Composition Example 1] Cream Capsiate 1.0wt%
Stearic acid 2.0
Polyoxyethylene (25) cetyl ether 3.0
Glyceryl monostearate 2.0
Octyldodecanol 10.0
Cetanol 6.0
Reduced lanolin 4.0
Squalane 9.0
1,3-butylene glycol 6.0
Polyethylene glycol (1500) 4.0
Preservatives Appropriate perfume Appropriate amount Antioxidant Appropriate amount

[Formulation Example 2] Emulsion Capsiate 2.0wt%
Sorbitan sesquioleate 2.0
Polyoxyethylene oleoyl ether 2.5
Stearyl alcohol 0.5
Hardened palm oil 3.0
Liquid paraffin 35.0
Dipropylene glycol 6.0
Polyethylene glycol (400) 4.0
Carboxyvinyl polymer (1% aqueous solution) 15.0
Preservative Appropriate amount of perfume Appropriate amount of purified water The remainder

[Formulation Example 3] Gelcapsiate 0.5 wt%
Liquid paraffin 12.0
Tri (2-ethylhexanoic acid) glyceryl 50.0
Sorbit 10.0
Polyethylene glycol (400) 5.0
Acylmethyl taurine 5.0
Polyoxyethylene (20) isocetyl ether 10.0
Perfume Appropriate amount Preservative Appropriate amount Purified water The rest

[Formulation Example 4] Essence liquid dihydrocapsiate 1.0 wt%
p-Methoxycinnamic acid-2-ethylhexyl 4.0
3,3 '-(1,4-phenylene dimethylidine)
Bis (7,7-dimethyl-2-oxo-
Bicyclo (2,2,1) heptane-1-methanesulfonic acid) 4.0
Polyoxyethylene cetyl ether 2.0
Glycerol monostearate 2.0
Stearic acid 3.0
Cetanol 1.0
Lanolin 3.0
Liquid paraffin 5.0
2-ethylhexyl stearate 3.0
1,3-butylene glycol 6.0
Perfume Appropriate amount Preservative Appropriate amount Purified water The rest

[Formulation 5] Toner lotion capsiate 3.0wt%
Glycerin 3.0
Sorbitol 2.0
Polyoxyethylene (20) oleyl ether 1.0
Ethanol 15.0
Zinc paraphenol sulfonate 0.2
Perfume Appropriate amount Preservative Appropriate amount Purified water The rest

[Composition Example 6] Hair restorer Capsiate 2.0 wt%
Assembly extract 0.1
Hyaluronic acid 0.2
Hinokitiol 0.2
Vitamin B6 0.5
Vitamin E 0.5
Urea 2.5
Propylene glycol 4.0
Ethanol 50.0
Perfume Appropriate amount Preservative Appropriate amount Purified water The rest

[Formulation Example 7] Jelly-like peel-off pack capsiate 2.0 wt%
Jojoba oil 1.0
Squalane 1.0
PEG400 5.0
Sorbitol 5.0
Ethanol 8.0
Polyvinyl alcohol 10.0
Polyvinyl acetate emulsion 15.0
Titanium oxide 5.0
Talc 10.0
POE sorbitan monostearate 1.0
Perfume Appropriate amount Preservative Appropriate amount Purified water The rest

[Formulation example 7] Milk bath capsiate 5.0 wt%
Liquid paraffin 55.0
Squalane 10.0
Macadamia nut oil 10.0
Sorbitan oleate 10.0
POE oleyl ether 10.0
Perfume Appropriate amount Preservative Appropriate amount

[Reference Example] Capsinoids used in capsinoid synthesis experiments were synthesized using fatty acid methyl esters or fatty acids according to the method described in Document 1 below or an improved method thereof. Typical examples are described below.
(1) Synthesis of vanillyl decanoate According to the method described in Reference 1 below, synthesis was performed as follows.
Decanoic acid methyl ester (2.13 ml, 10.5 mmol), vanillyl alcohol (1.62 g, 10.5 mmol), molecular sieves 4Å (10 g) and Novozyme 435 (2.5 g) were added to acetone (50 ml) and stirred at room temperature for 2 days. did. The reaction solution was filtered through celite, and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by silica gel chromatography to obtain 2.25 g (7.30 mmol, 73.0%) of vanillyl decanoate as a colorless oil.
¹ H-NMR (CDCl3, d): 0.87 (t, 3H, J = 7.1Hz), 1.18-1.30 (m, 12H), 1.55-1.65 (m, 2H), 2.33 (t, 2H, J = 7.7Hz ), 3.90 (s, 3H), 5.03 (s, 2H), 5.64 (br, 1H), 6.80-6.90 (m, 3H).
(2) Synthesis of Capsiate Using a trans-8-methyl-6-nonenoic acid methyl ester synthesized by the method described in Reference 2 below, synthesis was performed according to the method described in Reference 1 below.
¹ H-NMR (CDCl3, d): 0.95 (d, 6H, J = 6.74Hz), 1.33-1.40 (m, 2H), 1.59-1.67 (m, 2H), 1.94-1.99 (m, 2H), 2.18 -2.23 (m, 1H), 2.33 (t, 2H, J = 7.52Hz), 3.89 (s, 3H), 5.02 (s, 2H), 5.26-5.39 (m, 2H), 5.63 (br, 1H), 6.83-6.90 (m, 3H).
(3) Synthesis of dihydrocapsiate Commercially available 8-methylnonanoic acid was converted to a methyl ester, and was synthesized according to the method described in Document 1 below.
¹ H-NMR (CDCl3, d): 0.86 (d, 6H, J = 6.60Hz), 1.12-1.37 (m, 8H), 1.46-1.64 (m, 3H), 2.32 (t, 2H, J = 7.56Hz ), 3.89 (s, 3H), 5.02 (s, 2H), 5.63 (br, 1H), 6.83-6.90 (m, 3H).
(4) Synthesis of nordihydrocapsiate Using commercially available 7-methyloctanoic acid methyl ester, synthesis was performed according to the method described in Document 1 below.
¹ H-NMR (CDCl3, d): 0.86 (d, 6H, J = 5.64Hz), 1.10-1.16 (m, 2H), 1.22-1.32 (m, 4H), 1.42-1.68 (m, 3H), 2.33 (t, 2H, J = 7.68Hz), 3.90 (s, 3H), 5.02 (s, 2H), 5.63 (s, 1H), 6.83-6.90 (m, 3H).
(5) Synthesis of three capsinoid mixtures The three capsinoid mixtures used in the present invention were obtained by refluxing capsaicin in hydrous methanolic hydrochloric acid with reference to the method described in Reference 1 and vanilla. Enzymatically synthesized starting from ril alcohol was used. Specifically, the molar ratio of fatty acid methyl to vanillyl alcohol was 1: 5, the enzyme used was immobilized lipase (product name: Novozyme 435, manufactured by Novozyme), and the reaction conditions were 25 ° C. for 45 hours. The yield was 71.7%, the purity was 97.5% as capsinoid, and the abundance ratio of capsiate, dihydrocapsiate and nordihydrocapsiate was 62: 30: 7 by HPLC analysis.
(6) Synthesis of vanillyl octanoate A commercially available octanoic acid was used and synthesized according to the method described in Document 1 below.
¹ H-NMR (CDCl3, d): 0.88 (d, 3H, J = 7.10Hz), 1.20-1.35 (m, 8H), 1.60-1.70 (m, 2H), 2.35 (t, 2H, J = 7.40Hz ), 3.90 (s, 3H), 5.03 (s, 2H), 6.83-6.90 (m, 3H).
(7) Synthesis of vanillyl undecanoate Using commercially available undecanoic acid, it was synthesized according to the method described in the following document 1.
¹ H-NMR (CDCl3, d): 0.88 (d, 3H, J = 6.76Hz), 1.20-1.35 (m, 14H), 1.58-1.68 (m, 2H), 2.35 (t, 2H, J = 7.68Hz ), 3.90 (s, 3H), 5.03 (s, 2H), 6.83-6.90 (m, 3H).
(8) Synthesis of Vanillyl 9-methyldecanoate 9-Methyldecanoic acid was synthesized by a method improved from Reference 3 below and synthesized according to the method described in Reference 1.
¹ H-NMR (CDCl3, d): 0.86 (d, 6H, J = 6.64Hz), 1.12-1.35 (m, 10H), 1.45-1.55 (m, 1H), 1.50-1.60 (m, 2H), 2.34 (t, 2H, J = 7.44Hz), 3.89 (s, 3H), 5.03 (s, 2H), 6.83-6.90 (m, 3H).
(9) Synthesis of vanillyl 6-methyloctanoate 6-methyloctanoic acid was synthesized by a method improved from the following document 3 and synthesized according to the method described in document 1.
¹ H-NMR (CDCl3, d): 0.80-0.90 (m, 6H), 1.05-1.19 (m, 2H), 1.22-1.40 (m, 5H), 1.60-1.70 (m, 2H), 2.34 (t, 2H, J = 7.56Hz), 3.89 (s, 3H), 5.03 (s, 2H), 6.85-6.91 (m, 3H).
(10) Synthesis of vanillyl 7-methylnonanoate 7-methylnonanoic acid was synthesized by a method improved from the following document 3 and synthesized according to the method described in document 1.
¹ H-NMR (CDCl3, d): 0.80-0.90 (m, 6H), 1.05-1.20 (m, 2H), 1.20-1.38 (m, 7H), 1.60-1.70 (m, 2H), 2.34 (t, 2H, J = 7.72Hz), 3.90 (s, 3H), 5.03 (s, 2H), 6.85-6.91 (m, 3H).
(11) Synthesis of Vanillyl 8-methyldecanoate 8-Methyldecanoic acid was synthesized by a method improved from Reference 3 below and synthesized according to the method described in Reference 1.
¹ H-NMR (CDCl3, d): 0.80-0.90 (m, 6H), 1.02-1.20 (m, 2H), 1.20-1.40 (m, 9H), 1.60-1.70 (m, 2H), 2.34 (t, 2H, J = 7.72Hz), 3.90 (s, 3H), 5.03 (s, 2H), 6.85-6.91 (m, 3H).
(12) Synthesis of vanillyl n-tridecanoate, vanillyl n-pentadecanoate, vanillyl stearate, vanillyl oleate, vanillyl linoleate These compounds are commercially available n-tridecanoic acid, n-pentadecanoic acid, stearic acid, Using oleic acid and linoleic acid, they were synthesized according to the method described in the following document 1.
Reference 1
Enzymatic Synthesis of a Capsinoid by the Acylation of Vanillyl Alcohol with Fatty Acid Derivatives Catalyzed by Lipases.
Kenji Kobata, Manami Kawaguchi, and Tatsuo watanabe
Biosci. Biotechnol. Biochem., 66 (2), 319-327, 2002
Reference 2
A General and Stereoselective Synthesis of the Capsaicinoids via the Orthoester Claisen Rearrangement
Harumi Koga, Kouhei Goto, Tomiki Takahashi, Masao Hino, Takashi Tokuhashi and Kazuhiko Orito
Tetrahedoron, 52 (25), 8451-8470, 1996
Reference 3
A Short and Practical Synthesis of 8-Methylnonanoic Acid, a Synthon of Dihydrocapsaicin, via Grignard Coupling.
Sham A. Hassarajani, Seturam Mithran and Vasant R. Mamdapur
J. Chem. Research (S), 219, 1993

Claims (6)

  An agent for promoting blood circulation, comprising a capsinoid compound. The agent for promoting blood circulation according to claim 1, wherein the capsinoid compound is represented by the following general formula (1) or selected from compounds.

(In the general formula (1), R1 represents an alkyl group having 5 to 10 carbon atoms or an alkenyl group having 5 to 10 carbon atoms, and any of them may have a substituent (however, it does not have a substituent). Except octyl group)).   In the above general formula (1), R 1 is hexyl, heptyl, 6-methylheptyl, 5-methylheptyl, 7-methyloctyl, 6-methyloctyl, trans-7-methyl-5-octenyl. The blood circulation promoting external preparation according to claim 1 or 2, which is a group selected from the group consisting of a group, a nonyl group, an 8-methylnonyl group, a 7-methylnonyl group and a decyl group.   The capsinoid compound is capsiate, dihydrocapsiate, nordihydrocapsiate, vanillyl decanoate, vanillyl octanoate, vanillyl undecanoate, vanillyl 9-methyldecanoate, vanillyl 6-methyloctanoate, vanillyl 7- The blood circulation promoting external preparation according to any one of claims 1 to 3, which is selected from the group consisting of methylnonanoate, vanillyl 8-methyldecanoate, and a mixture thereof. A cosmetic for skin / hair and a bath containing the blood circulation promoting external preparation according to any one of claims 1 to 4. Any compound selected from vanillyl undecanoate, vanillyl 9-methyl decanoate, vanillyl 6-methyl octanoate, vanillyl 7-methyl nonanoate, vanillyl 8-methyl decanoate.