External pain relief agent containing ginger ingredients

Abstract

To produce a ginger extract with low odor and skin irritation, and to provide an external pain relief agent using the same.SOLUTION: The present invention is an external agent containing 50 wt.% or more of an extract obtained by extracting dried ginger (ZINGIBERIS PROCESSUM RHIZOMA) with vegetable oil, characterized by containing 10 to 200 ppm of 6-shogaol. It has little odor and skin irritation and particularly can be suitably used in relieving neuropathic pain and cold sensation by being used externally as a lotion or cream.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an external preparation for relieving pain, which contains a ginger component. [Background technology]

[0002] Ginger has been used as food since ancient times, and is also incorporated into herbal medicines as a cold medicine, stomachic, digestive, antiemetic, and analgesic. Its fever-inducing, sweat-inducing, and anti-inflammatory effects when taken orally are well known, and it is also used in cold medicines and health foods. Of these effects, the molecular biological mechanism of the anti-inflammatory effect has not been clear until now, but in recent years it has been reported that 6-shogaol has the effect of protecting nerve cells from oxidative stress (Non-Patent Document 1), and the possibility of such an effect due to protective action has been demonstrated. External preparations using ginger have also been developed, but are not common, and are expected to prevent skin aging by improving blood flow and improve moisturizing function (Patent Document 1).

[0003] Ginger is generally extracted by extraction with an organic solvent or steam distillation, as with other plant extracts. Ginger extract is generally obtained by extracting raw or dried ginger rhizomes with a hydrophilic organic solvent such as ethanol, and then concentrating the extract. Ginger essential oil is sold as an essential oil obtained by steam distillation of ginger rhizomes. These extracts are characterized by a very strong irritating odor. Ginger contains odorous components such as cineole and zingiberene, which are alcohol-soluble and low-boiling point compounds. Therefore, general extraction methods have the disadvantage that these odorous components are concentrated, which inevitably results in a strong irritating odor.

[0004] On the other hand, in the process of searching for a treatment for vitiligo vulgaris, we discovered a sesame oil extract of ginger (Patent Document 2), but this extract did not have the irritating odor of conventional extracts. It is presumed that the mechanism of improvement of vitiligo vulgaris is due in part to the action of 6-shogaol, one of the components contained in ginger, to protect melanocytes from oxidative stress (Non-Patent Document 2). Since melanocytes and nerve cells are similar cells, we thought that the action of protecting such cells from stress would also be effective in suppressing nerve inflammation and relieving pain, so we decided to investigate this. Many types of active ingredients such as ketoprofen and ibuprofen are known as topical agents for pain relief, but there are still few effective topical analgesics for neuropathic pain such as postherpetic neuralgia, so there is a considerable unmet need. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 2015-214519 [Patent Document 2] Patent Publication No. 2019-73448 [Non-patent literature]

[0006] [Non-Patent Document 1] Phtother.Res,Vol.27,ISSUE 12,2013,1795 [Non-Patent Document 2] Int.J.Mol.Sci,Vol.21,ISSUE10,2020,3537 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention provides a ginger extract that has little odor and skin irritation, and provides an external preparation for relieving pain using the extract. [Means for solving the problem]

[0008] As a result of extensive research, the inventors have found that by extracting dried ginger with vegetable oil, it is possible to obtain an extract with less odor and irritation, which can be suitably used for external preparations. This is believed to be because many of the compounds that are the source of ginger's odor are hydrophilic and therefore difficult to extract, and because the boiling point of vegetable oil is high, the diffusion of odorous components by mixed steam is unlikely to occur. The present invention has been completed based on this finding, and includes the following aspects. Item 1. An external preparation for relieving pain, which contains 50% by weight or more of an extract obtained by extracting dried ginger (kankyo) with vegetable oil, and contains 10 to 200 ppm of 6-shogaol. Item 2. The topical cream according to claim 1, which contains shea butter. Effect of the Invention

[0009] According to the present invention, an external preparation containing a ginger component with little odor can be obtained, which can be suitably used for purposes such as relieving neuropathic pain. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 summarizes the components of the topical pain-relieving preparation prepared in the examples. [Diagram 2] FIG. 2 summarizes the effects of the external preparations for pain relief prepared in the examples. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] 1. Topical agents The topical agent of the present invention contains an extract obtained by extracting dried ginger (Kankyo) with vegetable oil. From the viewpoint of extraction efficiency and storage stability, it is preferable to use dried powder of Kankyo as the extraction raw material. Dried powder of Kankyo can be easily procured from a Chinese medicine pharmacy in Japan.

[0012] The solvent for extraction is not particularly limited as long as it is a vegetable oil. Examples include olive oil, grape seed oil, sesame oil, etc., but sesame oil is preferred in terms of affinity with the skin, stability in terms of quality, and solidification point. The sesame oil is not limited, but it is preferable to use unroasted sesame oil. Since the components of roasted sesame oil are denatured by heating (about 150°C to 220°C) and deodorization processing, it is preferable to select oil that is not treated after extraction as much as possible.

[0013] In the present invention, it is preferable to heat-treat the vegetable oil to be used for about 10 to 30 minutes at 80 to 130° C. before carrying out the extraction operation. This treatment is expected to remove volatile components that may cause irritation.

[0014] The extract of the present invention can be obtained by soaking dried ginger in vegetable oil, leaving it at room temperature (about 15°C to 35°C) for about 30 minutes to 24 hours, preferably about 6 to 8 hours, and then removing solid matter by filtration to recover the liquid layer. The ratio of dried ginger to vegetable oil during extraction is preferably adjusted to 10 to 100 parts by weight of vegetable oil per 1 part by weight of dried ginger.

[0015] The concentration of the components extracted from dried ginger in the extract is positively correlated with the ratio of dried ginger to vegetable oil during extraction, but generally, if the ratio of solute to solvent is too large, the proportion remaining on the solute side increases, and the extraction efficiency decreases. If the ratio is too small, the amount of extracted components is too small, resulting in a low concentration of active ingredients, and if the ratio is too large, the extraction efficiency decreases and the active ingredients are not extracted very much, so the ratio is preferably about 1:10-100.

[0016] Since it is technically difficult to control all of the components extracted, it is preferable to control the compound concentration, which is an index of effectiveness, as a representative value. When 6-shogaol is used as a representative value as an index of concentration in the extract, its concentration is preferably 10 ppm or more and 200 ppm or less. The concentration of 6-shogaol depends on the amount contained in the raw material dried ginger and the amount ratio with the vegetable oil at the time of extraction, so management of each raw material is necessary. In addition, in the extraction method of the present invention, since concentration by volatilization of the solvent is technically difficult, there is an upper limit to the concentration of 6-shogaol contained in the extract. When the partition coefficient of 6-shogaol between dried ginger and general vegetable oil obtained by experiment and the literature value of 6-shogaol contained in dried ginger were examined, it was technically difficult to extract 6-shogaol exceeding 200 ppm by the extraction method of the present invention.

[0017] As mentioned above, 6-shogaol has been reported to protect nerve cells from damage such as oxidative stress, and is expected to reduce stress on nerve tissue caused by inflammation of nerve cells themselves or related cells, such as postherpetic neuralgia and arthralgia, and to alleviate pain. Although there are individual differences, the pain-relieving effect can be obtained within the above concentration range.

[0018] For example, it is possible to obtain a similar composition by mixing an alcohol extract or essential oil containing 6-shogaol with a carrier such as vegetable oil or ethanol, but these extracts and essential oils contain many irritating components including odorous components, resulting in a composition that is very irritating to the skin and is not suitable for practical use. For this reason, the topical agent of the present invention is obtained by directly extracting dried ginger with vegetable oil.

[0019] The topical preparation of the present invention can be prepared by using the above extract without diluting it or by mixing the above extract with the following base raw material. The topical preparation of the present invention can be in the form of a cream or liquid, preferably an oily cream.

[0020] The base material is preferably hydrophobic. The topical preparation of the present invention is expected to promote the penetration of the active ingredient into the skin by sesame oil. In addition, the hydrophobic base is expected to facilitate the active ingredient to pass through the barrier function of the skin. Therefore, in order not to interfere with these actions, it is preferable not to use excess water or a surfactant that emulsifies the water and the hydrophobic base material in the topical preparation of the present invention.

[0021] The base raw material of the topical preparation of the present invention is not particularly limited as long as it is one that can be used to prepare medicines, quasi-drugs, and cosmetics.

[0022] Base ingredients include oils and fats (avocado oil, camellia oil, rice bran oil, safflower oil, soybean oil, corn oil, rapeseed oil, apricot kernel oil, persic oil, sunflower oil, peach kernel oil, cottonseed oil, coconut oil, wheat germ oil, rice germ oil, evening primrose oil, hybrid sunflower oil, macadamia nut oil, meadowfarm oil, hazelnut oil, olive oil, castor oil, sesame oil, almond oil, grapeseed oil, shea butter, palm kernel oil, palm oil, coconut oil, cocoa butter, wood wax, argan oil, rosehip oil, mink oil, turtle back oil, etc.) Oil, egg yolk oil, beef tallow, milk fat, lard, horse oil, etc.), hydrocarbons (vegetable squalene, vegetable squalane, petrolatum, microcrystalline petrolatum, squalene, squalane, liquid paraffin, paraffin, soft isoparaffin, liquid isoparaffin, liquid polyisobutylene, hydrogenated polyisobutylene, ozokerite, ceresin, synthetic squalane, α-olefin oligomer, polybutene, polyethylene, etc.), fatty acid esters (isopropyl myristate, isopropyl palmitate, butyl stearate, ethyl oleate, cetyl palmitate, myristic Myristyl myristylate, octyldodecyl myristic acid, octyldodecyl oleate, cholesteryl stearate, cholesteryl hydroxystearate, tricaprylin, trimyristin, trioctanoin, isopropyl isostearate, ethyl isostearate, cetyl ethylhexanoate, stearyl ethylhexanoate, glyceryl triethylhexanoate, trimethylolpropane triethylhexanoate, etc., pentaerythrityl tetraethylhexanoate, glyceryl triisostearate, trimethylolpropane triisostearate, tetraisostearate, etc. Pentaerythrityl stearate, isocetyl isostearate, octyldodecyl dimethyloctanoate, myristyl lactate, cetyl lactate, trioctyldodecyl citrate, diisostearyl malate, etc.), waxes (beeswax, lanolin, reduced lanolin, jojoba oil, carnauba wax, candelilla wax, rice bran wax, orange roughy oil, shellac, montan wax, etc.), higher fatty acids (lauric acid, stearic acid, myristic acid, palmitic acid, behenic acid, oleic acid, linoleic acid, ethylhexanoic acid, isostearic acid, isopalmitic acid, isotridecanoic acid,isononanoic acid, pentadecanoic acid, etc.), higher alcohols (lauryl alcohol, stearyl alcohol, cetearyl alcohol, behenyl alcohol, oleyl alcohol, lanolin alcohol, cetanol, cholesterol, isocholesterol, sitosterol, stigmasterol, isostearyl alcohol, octyldodecanol, hexyldecanol, etc.), silicone oils, etc.

[0023] The base raw material is preferably at least one selected from the group consisting of oils and fats (avocado oil, camellia oil, rice bran oil, macadamia nut oil, hazelnut oil, olive oil, castor oil, sesame oil, almond oil, grape seed oil, shea butter, palm kernel oil, palm oil, coconut oil, cocoa butter, wood wax, argan oil, rosehip oil), hydrocarbons (vegetable squalene, vegetable squalane, petrolatum, microcrystalline petrolatum, squalene, squalane, synthetic squalane), and waxes (beeswax, lanolin, reduced lanolin, jojoba oil, carnauba wax, candelilla wax, rice bran wax). The base raw material is more preferably sesame oil, sweet almond oil, vegetable squalane, squalane, petrolatum, beeswax, shea butter, jojoba oil, etc. The base raw material is even more preferably shea butter. The softening point of shea butter is close to body temperature, making the mixture highly compatible with the skin and ideal for use.

[0024] When the extract is diluted with a base material, the content of the extract may be in the range of 50 to 80% by weight, assuming that the total amount of the topical preparation is 100% by weight. The purpose of dilution is to thicken the topical preparation to make it creamy, and by adding 20 to 50% by weight of a solid component such as shea butter or beeswax, it is possible to adjust the topical preparation to the desired viscosity and softening point.

[0025] Since the topical preparation of the present invention is based on vegetable oil, it is preferable to contain a vitamin E compound, which is an antioxidant. Examples of vitamin E compounds include tocopherol, tocopherol acetate, tocopherin, and tocopherin acetate. The content of the vitamin E compound may be in the range of 0.01 to 5% by weight, assuming that the total amount of the topical preparation is 100% by weight.

[0026] The topical preparation of the present invention may contain additives such as plant extracts (essential oils, leached oils, dried extracts, etc.) other than ginger that have anti-inflammatory effects, antibacterial effects, antifungal effects, wound healing effects, skin roughness prevention effects, sebum secretion suppression effects, etc., bactericides, preservatives, antioxidants, etc.

[0027] Other plant extracts besides dried ginger include calendula extract (flower essential oil, infused oil, tincture, extract, etc.), arnica extract (flower infused oil, etc.), sage extract (leaf essential oil, infused oil, tincture, extract, etc.), rosemary extract (leaf essential oil, infused oil, tincture, extract, etc.), tea tree extract (leaf essential oil, etc.), neem extract (neem oil squeezed from the kernel of the fruit using a press, etc.), burdock extract (root infused oil, extract, etc.), eucalyptus extract (leaf essential oil, etc.), lavender extract (flower essential oil, tincture, extract, etc. Examples of the extracts include ginger, aromatic distilled water, lemon balm extract (leaf essential oil, etc.), Houttuynia cordata extract (leaf tincture, extract, etc.), Job's tears extract (fruit extract, tincture, etc.), heather extract (flower extract, tincture, etc.), Ecceana extract (whole plant tincture, extract, etc.), Malva sylvestris extract (flower or leaf extract, tincture, etc.), German chamomile (extract flower essential oil, tincture, extract, etc.), marshmallow extract (root or leaf extract, etc.), yarrow extract (flower essential oil, extract, tincture, etc.). Preferred are calendula extract (particularly calendula oil), tea tree extract (leaf essential oil), Houttuynia cordata extract (particularly leaf tincture, extract), Job's tears extract (fruit extract, tincture, etc.), and particularly preferred is calendula oil. A small amount of ginger extract can be added for the purpose of adjusting the concentration of the active ingredient.

[0028] These plant extracts may be prepared according to known methods, but can also be purchased from Tree of Life Co., Ltd., Naturas Psychos (Herbal Index LLC), Neal's Yard Remedies, etc.

[0029] Examples of disinfectants or preservatives include benzoic acid, dehydroacetic acid, phenylethanol, phenoxyisopropyl alcohol, hydroxybenzoic acid esters, chlorcresol, benzalkonium chloride, benzethonium chloride, chlorhexidine, propylene glycol, paraoxybenzoic acid esters, sorbite acid, and thymol.

[0030] Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, arbutin, kojic acid, ellagic acid, rucinol, vitamin C and its derivatives, and linoleic acid.

[0031] When the extract is a dried extract, the content of the plant extract other than dried ginger may be in the range of 0.001 to 5% by weight when the total amount of the external preparation is taken as 100% by weight, and the lower limit of the content of the dried extract is preferably 0.01% by weight, more preferably 0.05% by weight. The upper limit of the content of the dried extract is preferably 2% by weight, more preferably 1% by weight.

[0032] In the case where the plant extract other than dried ginger is an infused oil, the plant extract may be contained in a range of 5 to 50 volumes when the total volume of the external preparation is 100 volumes, and the content can be adjusted within a range that can maintain the shape of the dosage form. The lower limit of the content of the plant infused oil is preferably 20 volumes. The upper limit of the content of the plant extract is preferably 50 volumes.

[0033] In the case where the plant extract other than dried ginger is an essential oil, the plant extract may be contained in a range of 0.01 to 1 volume when the total volume of the external preparation is 100 volumes, and the content can be adjusted within a range that can maintain the shape of the dosage form. The lower limit of the content of the plant-infused oil is preferably 0.1 volume. The upper limit of the content of the plant extract is preferably 0.3 volume.

[0034] Other additives may include ultraviolet absorbing agents (para-aminobenzoic acid and its derivatives, cinnamic acid and its derivatives, benzophenone and its derivatives, salicylic acid and its derivatives, etc.), ultraviolet scattering agents (titanium oxide, zinc oxide, etc.), and biological components (collagen, hyaluronic acid, ceramide, hormones, placenta extracts, etc.).

[0035] Furthermore, coloring materials, fragrances (essential oils such as those of rose, geranium, lavender, mint, lemon, neroli, grapefruit, orange, etc.), and pH adjusters (phosphoric acid, citric acid, sodium citrate, lactic acid, diisopropanolamine, acetic acid, sodium acetate, succinic acid, sodium succinate, malic acid, sodium malate, etc.) may be added to the topical preparation of the present invention as necessary.

[0036] Additives such as bactericides, preservatives, antioxidants, ultraviolet absorbers, and biological components can be added appropriately within the range of 0.00001 to 10% by weight of the topical agent. The content of each ingredient contained in the base of each dosage form can be appropriately set within a range that allows the dosage form to be prepared to be maintained.

[0037] 2. Preparation method for topical preparation The topical preparation of the present invention can be prepared by known methods. For example, the extract of the present invention is heated to about 60-80°C, the above-mentioned raw materials or other extracts are added, and the mixture is mixed for about 5-10 minutes. Addition of additives such as vitamin E compounds and essential oils is followed by stirring, and insoluble matters are filtered to obtain a liquid preparation. If a high melting point base material such as beeswax is added, a topical composition in the form of a cream or the like can be prepared after cooling.

[0038] 3. Use of topical preparations and treatment methods The topical preparation of the present invention can be used as a drug, a quasi-drug, or a cosmetic. Here, the term "cosmetics" includes medicated cosmetics (cosmetics containing active ingredients) as defined in the "Law on Ensuring Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, etc."

[0039] The topical preparation of the present invention is expected to relieve pain by protecting nerve cells due to the components contained in ginger, and to maintain moisturizing and skin function by increasing heat, sweating, and blood flow. EXAMPLES

[0040] Examples of the present invention will be described below, but the present invention is not limited to the following examples.

[0041] Preparation of topical preparations External preparations were formulated according to the following Examples 1 to 4 and Comparative Examples 1 and 2. The dried ginger used was purchased from a Chinese herbal medicine store, and the sesame oil was purchased from Summit Essential Oils Co., Ltd. Tocopherol and various essential oils were purchased from those generally available commercially as cosmetic raw materials.

[0042] Example 1 100g of sesame oil was preheated at 80℃ for 30 minutes. After that, heating was stopped, 1g of dried ginger powder was added, and the mixture was left to cool naturally for 24 hours. 0.3g of tocopherol was added to the obtained extract, and the mixture was dissolved by stirring at room temperature for 10 minutes. After dissolution, the extraction residue was removed using a filter capable of cutting 1μm particles, and topical agent 1 was obtained. The content of ginger-derived components in the obtained topical agent 1 was analyzed by high performance liquid chromatography at the Japan Food Analysis Center (foundation). As a result, the concentration of 6-shogaol was 17ppm.

[0043] Example 2 100g of sesame oil was preheated at 80℃ for 30 minutes. After that, heating was stopped, 10g of dried ginger powder was added, and the mixture was left to cool naturally for 24 hours. 0.3g of tocopherol was added to the extract, and the mixture was stirred at room temperature for 10 minutes to dissolve. After dissolution, the extraction residue was removed using a filter capable of cutting 1μm particles, and topical agent 2 was obtained. The concentration of 6-shogaol in the obtained topical agent 2 was 77ppm.

[0044] Example 3 100g of sesame oil was preheated at 80℃ for 30 minutes. After that, heating was stopped, 3g of dried ginger powder was added, and the mixture was left to cool naturally for 24 hours. 0.3g of tocopherol was added to the extract, and the mixture was stirred at room temperature for 10 minutes to dissolve. After dissolution, the extraction residue was removed using a filter capable of cutting 1μm particles, and topical agent 3 was obtained. The concentration of 6-shogaol in the obtained topical agent 3 was 35ppm.

[0045] Example 4 100 g of the topical agent 2 obtained in Example 3 was placed in a glass container, 15 g of shea butter and 15 g of beeswax were added, and the mixture was heated and stirred at 70°C for about 10 minutes until the shea butter and beeswax were completely dissolved, and then cooled to obtain a cream-like topical agent 4. The concentration of 6-shogaol in the obtained topical agent 4 was 60 ppm.

[0046] Comparative Example 1 100 g of sesame oil was preheated for 30 minutes at 80° C. 0.1 g of commercially available ginger essential oil (manufactured by Incent Co., Ltd.) was added to prepare Comparative Agent 1.

[0047] Comparative Example 2 100 g of sesame oil was preheated for 30 minutes at 80° C. 0.5 g of commercially available ginger essential oil (manufactured by Incent Co., Ltd.) was added to prepare Comparative Agent 2. The composition of each topical composition is shown in Figure 1. Evaluation method

[0048] Five volunteers were asked to apply the topical preparations of Examples 1 to 5 and Comparative Examples 1 to 2 to the painful area, and were asked to answer a questionnaire about whether they felt warm (warm sensation), the pain relieving effect, and whether there was an odor after use. As a result, for Example 1, three out of five people answered that they felt the effect, and two people answered that they did not feel the effect. For Examples 2 to 5, all people answered that they felt the effect. For the odor after use, for all Examples 1 to 5, they answered that "there is no odor" or "it doesn't bother me." On the other hand, for Comparative Examples 1 and 2, all people answered that they felt no effect and that there was a strong irritating odor after use. The results of the evaluation are shown in Figure 2.

[0049] Although it is difficult to attribute the effects of the results of this evaluation to a single component, the inventors believe that 6-shogaol is one of the active ingredients. Therefore, the concentration of 6-shogaol is the control item in the extraction. The extraction method of the present invention is characterized by a relatively small amount of components that cause irritating odors, and perhaps because of this, there were no side effects when used externally and the odor was at an unnoticeable level. Since the odor is low, it is possible to adjust the odor of the external agent by adding other essential oils. In addition, the base material is lipophilic, so it penetrates the skin quickly, and the effect was immediate.

Claims

1. An external preparation for relieving pain, comprising 50% by weight or more of an extract obtained by extracting dried ginger (kankyo) with vegetable oil, and containing 10 to 200 ppm of 6-shogaol.

2. 2. The topical cream according to claim 1, which contains shea butter.

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