The present invention relates to a skin moisturizer and a blood circulation promoter. The present invention further relates to external preparations for the skin comprising the skin moisturizer or the blood circulation promoter and thus having excellent moisturizing effects or blood circulation-promoting effects.
The water content of the horny layer of the skin is closely connected with the condition of the skin. To maintain healthy bare skin, an appropriate amount of water needs to be retained in the horny layer. It is known that natural moisturizing factors (NMF) greatly contribute to the water retention of the horny layer (see Non-patent Document 1). In particular, amino acids, which are the main components of NMF, are considered to be deeply involved in the water retention of the horny layer. However, it has been reported that the amount of amino acids in the horny layer decreases with age or is reduced due to the external environment, which results in reduced water retention function of the horny layer (see Non-Patent Documents 2 and 3). This reduction in the water retention function of the horny layer is one of the factors that cause wrinkles to be formed because of reduced skin moisture and reduced elasticity with age.
To improve such water retention function and enhance the moisture retention of the skin, various types of moisturizers (such as glycerin, propylene glycol, sorbit, trehalose, 1,3-butylene glycol, hyaluronic acid, and sodium salts thereof) have been developed, and made commercially available. By application to the skin, such moisturizers inhibit transepidermal water loss (TEWL) and retain the water content of the skin, thus providing skin moisturizing effects. Urea is one of the components of NMF, and is widely used as a moisturizer. As part of the moisturizing mechanism of urea in the horny layer, “hydrogen bonding” is considered to retain water in the horny layer and prevent the skin from drying.
There have been various natural product-derived components proposed for use as moisturizers, such as plant extracts and bacteria cell extracts (see, for example, Patent Documents 1 to 6). Patent Documents 1 to 6 specifically describe that extracts of banyan and plants of the families Cunoniaceae, Welwitschiaceae, Hydrophyllaceae and Fouquieriaceae are effective as moisturizers and bacteria cell activators.
Patent Document 7 describes that extracts of plants belonging to the genus Blechnum of the family Blechnaceae of the order Filicales and plants belonging the genus Polystichum of the family Dryopteridaceae have cell-activating properties and are effective as antioxidants.
Many attempts have been made to utilize plant extracts as moisturizers or cell activators, as described above. However, such moisturizers and cell activators do not have sufficient effects, and are far from being completely satisfactory. Thus, an object of the present invention is to find a natural-product component having excellent moisturizing effects and a natural-product component capable of promoting blood flow to activate cells, and provide a skin moisturizer and a blood circulation promoter each utilizing such an excellent component. Another object is to provide external preparations for the skin utilizing the moisturizing effects of the skin moisturizer and the blood circulation-promoting effects (blood flow-enhancing effect) of the blood circulation promoter.
To achieve the above objects, the present inventors conducted extensive research, and found that a plant belonging to the genus Litsea of the family Lauraceae has excellent skin-moisturizing effects and blood circulation-promoting effects. As a result of this research, the inventors confirmed that a processed product of the above-mentioned plant can be used as an active ingredient of external preparations for the skin that have moisturizing effects and blood circulation-promoting effects. The present invention has been accomplished, based on this finding.
Thus, the present invention provides the following items:
The present invention can provide a skin moisturizer having excellent moisturizing effects, and provide a blood circulation promoter having blood flow-promoting effects. The skin moisturizer can be effectively used as a moisturizing component of external preparations for the skin that have moisturizing effects (such as cosmetics and external pharmaceuticals), particularly cosmetics. The blood circulation promoter can be used as a blood circulation-promoting component of external preparations for the skin that have blood flow-promoting effects (such as external pharmaceuticals and cosmetics).
The present invention can provide external preparations for the skin (such as cosmetics and external pharmaceuticals) containing the above skin moisturizer as an active ingredient and thus having excellent moisturizing effects. Further, the present invention can provide external preparations for the skin (such as cosmetics and external pharmaceuticals) containing the above blood circulation promoter as an active ingredient and thus promoting blood flow in the face, head, limbs or the whole body to prevent and ameliorate disorders (such as skin dullness, age spots, wrinkles, hair loss, and thinning hair due to reduced metabolism) and pathologic conditions (such as suffering from sensitivity to cold due to poor circulation, stiff shoulders associated with poor circulation, congestion, bedsores, Raynaud's disease, and economy-class syndrome), all caused by blood circulation disorders.
Any plant that belongs to the genus Litsea of the family Lauraceae can be used as the plant in the present invention. Specific examples thereof include Litsea acuminata, Litsea lancifolia (Sieb. et Zucc.) F. Vills., Litsea japonica, Litsea calicaris, Litsea cubeba, Litsea ichangensis, Litsea citrata, Litsea polyantha, and the like. Litsea polyantha is preferable.
Any portion of the plant can be used in the present invention. The whole plant or a part of the plant (such as leaves, flowers, seeds, roots, stems, and buds) may be used. The leaves, roots, stems, barks, and seeds are preferable from the viewpoint of the ease of availability. Using the leaves or seeds, particularly leaves, is preferable from the viewpoint of efficacy.
Examples of the processed products of the present invention include crushed products, pulverized products, juices, and extracts of the whole plant or a part of the plant. Such crushed products or pulverized products may be used as is or after being dried.
The whole plant or a part of the plant, as is or after being dried, may be subjected to solvent extraction. Considering extraction efficiency, the whole plant or a part of the plant is preferably subjected to extraction after processing such as slicing and pulverization. The extraction may be performed by immersion in an extractant or by supercritical fluid extraction or subcritical fluid extraction. Stirring or homogenization in the extractant may be performed to enhance extraction efficiency. The extraction temperature is not particularly limited. For example, a temperature in the range of about 5° C. to a temperature not higher than the boiling point of the extractant may be used. The extraction time may vary according to the type of extractant and the extraction temperature used. The extraction time is usually about 1 hour to about 14 days.
Examples of extractants include water; lower alcohols such as methanol, ethanol, propanol, and isopropanol; polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, and dipropylene glycol, and glycerin; ethers such as ethyl ether, and propyl ether; esters such as butyl acetate, and ethyl acetate; ketones such as acetone, and ethyl methyl ketone; chloroform, dichloromethane, and like organic solvents. Organic solvents that are capable of extracting a lipid-soluble fraction from the above-mentioned plant are preferably used. The extractants may be used singly or as a mixture of two or more thereof. Examples of such solvent mixtures include a mixture of chloroform with methanol or ethanol. One or more kinds of supercritical fluids or subcritical fluids such as carbon dioxide, ethylene, propylene, ethanol, methanol, and ammonia may be used.
As the processed product of the invention, the thus obtained solvent extract of a plant of the genus Litsea may be used as is, or the extract may further be concentrated or dried, dissolved again in a nonpolar solvent, and used. As long as the effects of the present invention are not impaired, the extract may be subjected to purification, such as decolorization, deodorization, and desalting, or fractionated by column chromatography, etc., and the obtained fraction may be used as a processed product of the invention. The extract of a plant of the genus Litsea, processed products thereof, and fractionated products thereof may be lyophilized, and dissolved when used.
The processed product of a plant of the genus Litsea has excellent moisturizing effects as shown in Experiment 1 below, and therefore can be used as an active ingredient of skin moisturizers, particularly skin moisturizers in an epidermally administrable form. More specifically, the present invention can provide a skin moisturizer in an epidermally administrable form containing the processed product of a plant of the genus Litsea as an active ingredient.
The proportion of the processed product of a plant of the genus Litsea in the skin moisturizer of the invention is not particularly limited, as long as the obtained skin moisturizer has moisturizing effects. The proportion can be appropriately selected from the range of 0.1 to 100 wt. %, preferably 1 to 100 wt. %, and more preferably about 2.5 to 100 wt. %, based on the total weight.
The form of the moisturizer is not particularly limited, as long as the moisturizer is epidermally administrable. Examples of such forms include liquids, emulsions, creams, ointments, gels, aerosols, and patches such as packs.
The skin moisturizer of the invention can be used as an active ingredient of external preparations for the skin having moisturizing effects. Such an external preparation for the skin contains the skin moisturizer as an essential ingredient and may further contain other components usually contained in external preparations for the skin (such as drugs, quasi drugs, skin cosmetics, hair cosmetics, washes). Examples of such components include surfactants (such as emulsifiers), oily components, alcohols, solubilizers, thickeners, antioxidants, chelating agents, pH adjusters, Flavoring agents, coloring matter, UV absorbers, UV-scattering agents, vitamins, amino acids, and preservatives.
Other moisturizers may be incorporated as long as the effects of the present invention are not impaired. Any moisturizer may be used, and examples of usable moisturizers include polyhydric alcohols, such as glycerol, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerols, polyethylene glycol, and dipropylene glycol; NMF components such as amino acids, sodium lactate, and sodium pyrrolidone carboxylate; and water-soluble high polymers, such as hyaluronic acid, collagen, mucopolysaccharides, and chondroitin sulfate.
The proportion of the skin moisturizer of the invention in the external preparation for the skin is not particularly limited, as long as the obtained external preparation for the skin has moisturizing effects attributable to the skin moisturizer of the invention. In general, the proportion can be appropriately selected from the range of 0.1 to 100 wt. %, preferably 1 to 100 wt. %, and more preferably 2.5 to 100 wt. %, based on the dry weight of the plant of the genus Litsea.
The form of the external preparation for the skin is not particularly limited. Examples of such forms include lotions (liquids, dispersions), emulsions, creams, ointments, aerosols, foams, patches such as poultices and packs, external pharmaceuticals, skin cosmetics, scalp cosmetics, and hair cosmetics (such as hair growth stimulants, hair conditioners), and washes (such as body washes, hair washes, and facial washes).
The processed product of a plant of the genus Litsea has excellent blood circulation-promoting effects as shown in Experiment Example 2 below, and therefore can be used as an active ingredient of blood circulation promoters that have blood flow-promoting effects. More specifically, the present invention can provide a blood circulation promoter in an epidermally administrable form containing a processed product of a plant of the genus Litsea as an active ingredient.
The proportion of the processed product of a plant of the genus Litsea in the blood circulation promoter of the invention is not particularly limited, as long as the obtained blood circulation promoter has blood flow-promoting effects. The proportion can be appropriately selected from the range of 0.1 to 100 wt. %, preferably 1 to 100 wt. %, and more preferably 2.5 to 100 wt. %, based on the total weight.
The form of the blood circulation promoter is not particularly limited, as long as the promoter is epidermally administrable. Examples of such forms include liquids, emulsions, creams, ointments, gels, aerosols, and patches such as packs.
The blood circulation promoter of the invention can also be used as an active ingredient of external preparations for the skin that have blood flow-promoting effects. Such an external preparation for the skin contains the blood circulation promoter as an essential ingredient, and optionally contains other components usually contained in external preparations for the skin (such as drugs, quasi drugs, skin cosmetics, scalp cosmetics, and washes). Examples of such components include surfactants (such as emulsifiers), oily components, alcohols, solubilizers, thickeners, antioxidants, chelating agents, pH adjusters, Flavoring agents, coloring matters, UV absorbers, UV-scattering agents, vitamins, amino acids, and preservatives.
Other blood circulation promoters may be incorporated, as long as the effects of the invention are not impaired. Any blood circulation promoter may be used, and examples of promoters that can be incorporated include capsicum tincture, γ-orizanol, and the like.
The proportion of the blood circulation promoter of the invention in the external preparation for the skin is not particularly limited, as long as the obtained external preparation for the skin has blood circulation-promoting effects attributable to the blood circulation promoter of the invention. In general, the proportion can be appropriately selected from the range of 0.1 to 100 wt. %, preferably 1 to 100 wt. %, and more preferably 2.5 to 100 wt. %, based on the dry weight of the plant of the genus Litsea.
The form of the external preparation for the skin is not particularly limited. Examples of such forms include lotions (liquids, dispersions), emulsions, creams, ointments, aerosols, foams, patches such as poultices, and packs, external pharmaceuticals, skin cosmetics, scalp cosmetics, and hair cosmetics (such as hair growth stimulants and hair conditioners), and washes (such as body washes, hair washes and facial washes). The external skin preparation, which contains the blood flow promoter of the invention as an active ingredient, can promote blood flow in the face, head, limbs or the whole body to thereby prevent or ameliorate disorders (such as skin dullness, age spots, wrinkles, hair loss, and thinning hair due to reduced metabolism) and pathologic conditions (such as suffering from sensitivity to cold due to poor circulation, stiff shoulders associated with poor circulation, congestion, bedsores, Raynaud's disease, and economy-class syndrome), all caused by blood circulation disorders.
The following Experimental Examples serve to illustrate the invention in more detail, without limiting the scope of the invention. In the Examples, all percentages are by weight unless otherwise specified.
Urea was dissolved in an equal amount of water, and the resulting solution was mixed with a base cream (ingredients: dipropylene glycol, cetanol, 1,3-butylene glycol, stearyl alcohol, glyceryl stearate, stearic acid, polyethylene glycol-75, steareth-20, ceteth-20, jojoba oil, hydrogenated polyisobutene, ethoxydiglycol behenate, phenoxyethanol, ethylparaben, and methylparaben) to prepare a cream containing 10 wt. % of urea (a urea-containing cream).
Male Wister rats housed under a constant cycle of 12 hours of light (lights on from 7:00 to 19:00 at 80 lux) and 12 hours of darkness (19:00 to 7:00) for 1 week (body weight: 250 to 300 g) were used as experimental subjects (non-human subjects). Before the experiment, food (“MF” type; product of Oriental Yeast) and water were freely available to the rats.
To prevent the effect of smell stimulus on the sympathetic nerve, every day, starting from five days before the experiment, a 1% aqueous zinc sulfate solution was applied to the nasal mucosa of each experimental subject under pentobarbital anesthesia (30mg/kg) and allowed to stand for 10 minutes for anosmia treatment (Kolunie J M. Stern J M: Horm Behav 1995, 29:492-518).
After the rats were subjected to fasting for 6 hours, 2 g of the urea-containing cream or the base cream as a control was applied to the tail of each rat under urethane anesthesia (with an aqueous solution of urethane being intraperitoneally administered in an amount of 1 g/kg of body weight). The changes in nerve activity (electrical activity) of the efferent branches of the cutaneous arterial sympathetic nerves were measured for 60 minutes, immediately after application.
More specifically, the measurement of electrical activity in the cutaneous arterial sympathetic nerve (efferent branch) was performed by hooking up efferent branch of cutaneous arterial sympathetic nerve fibers of each rat with a pair of silver-wire electrodes under a stereoscopic microscope. To prevent drying, the electrodes were immersed in a mixture of liquid paraffin and a mixture of warm vaseline. The obtained electrical activity in the nerve was amplified with a differential amplifier and monitored using an oscilloscope. To detect nerve activity in the cutaneous arterial sympathetic nerve, noise signals were separated by a window discriminator, and converted to spike signals. The obtained spike signals were counted, based on the number of spikes per 5 seconds, using a rate meter, then subjected to A/D (analog/digital) conversion, and recorded on a personal computer (see
The above results show that application of a 10% urea-containing cream to the skin reduces activity in the sympathetic nerve that controls the cutaneous artery. In contrast, when the base cream was applied to the tail of rat (control rat), no substantial change was observed in the nerve activity (electrical activity) of the skin sympathetic nerve, compared to the activity before application of the cream, and such a reduction as seen in the test rat was not observed.
160 mg of the 10% urea-containing cream prepared in Reference Experimental Example (I) was applied to a skin area of 2×6 cm (12 cm2) on the left side of the back of male HWY (Hairless Wistar Yagi) rats weighing about 250 g, without using anesthesia, whereas 160 mg of a base cream as a control was applied to a skin area of 2×6 cm (12 cm2) on the right side of the back of the same. Eighteen hours and twenty-four hours after application, a portable evaporimeter (“VapoMeter”, product of Delfin Technologies Ltd) was pressed against each skin area thus treated to measure the transepidermal water loss (TEWL).
The experimental results confirmed that the application of a cream containing 10% of urea known as a moisturizer (urea-containing cream) to the skin reduces the transepidermal water loss (Experiment (II)) and concurrently reduces activity (electrical activity) in the cutaneous arterial sympathetic nerve. The results show that there is a correlation between the moisturizing effect on the skin and activity (electrical activity) in the cutaneous arterial sympathetic nerve, so that by measuring the activity (electrical activity) in the cutaneous arterial sympathetic nerves and using the reduction of such activity as an index, the moisturizing effects of test substances on the skin can be evaluated.
The electrical activity in cutaneous arterial sympathetic nerves (efferent branches) and the transepidermal water loss were measured according to the methods described in (I) and (II) of the Reference Experimental Examples, using as test samples pulverized leaves and solvent extracts of the leaves of Litsea polyantha (hereinafter simply referred to as “Litsea”), that is a plant belonging to the genus Litsea of the family Lauraceae.
Two grams each of a base cream (ingredients: dipropylene glycol, cetyl alcohol, 1,3-butylene glycol, stearyl alcohol, glyceryl stearate, stearic acid, polyethylene glycol-75, steareth-20, ceteth-20, Jojoba oil, hydrogenated polyisobutene, ethoxydiglycol behenate, phenoxyethanol, ethylparaben, and methylparaben) was mixed with each of the pulverized leaves of Litsea and the solvent extracts of the leaves of Litsea to prepare creams containing Litsea (Litsea-containing creams) as test samples.
A lipid-soluble fraction and a water-soluble fraction obtained in the methods described below were used as the solvent extracts.
Each of the Lipid-soluble fraction and the water-soluble fraction was mixed with 2 g each of the base cream, and used as test samples (a lipid-soluble fraction sample and a water-soluble fraction sample).
These results clearly show that when the base cream (control) was applied to the tails of the rats, the activity (electrical activity) in the cutaneous arterial sympathetic nerve hardly changed, compared to that before application of the base cream; in contrast, when the Listea-containing cream was applied to the tails of the rats, the activity of the cutaneous arterial sympathetic nerve was significantly reduced. The application of the Litsea-containing cream to the skin reduced the activity of the sympathetic nerves that control the cutaneous arteries (
The results show that Litsea, which is a plant belonging to the genus Litsea of the family Lauraceae, has an effect of inhibiting water loss from the skin and thereby enhancing the moisture retention of the skin (moisturizing effect).
These results clearly show that when the cream containing the lipid-soluble fraction of Litsea was applied to the tails of the rats, the activity in the cutaneous arterial sympathetic nerve was reduced; in contrast, the application of the water-soluble fraction of Litsea did not reduce the activity (electrical activity) in the cutaneous arterial sympathetic nerve. These results suggest that the lipid-soluble fraction of Litsea is a fraction with skin-water retention activity, and the fraction contains an active ingredient for producing moisturizing effects.
Two grams of the Litsea-containing cream containing pulverized leaves of Litsea (50 mg/2 g)(see Experiment Example 1) or the base cream (control) was applied to the tails and hairless portions of male Wistar rats (body weight: about 350 g). A tip of a laser blood flowmeter (“ADVANCE LASER FLOWMETER ALF21”, product of Advance) was attached to a fixed point of the stem of the tail using surgical tape, and the blood flow was measured. The values measured in terms of ml/min/100 g of the tissue were expressed as percentages, with the measured value before the cream application being defined as 100%. The absolute values, that are the 0 min values, were in the range of 3 to 5 ml/min/100 g of the tissue.
Cutaneous arteries are controlled by the sympathetic nerve, and noradrenaline emitted from sympathetic nerve endings constricts cutaneous blood vessels via α1 and α2 adrenergic receptors (W. F. Ganon, Review of Medical Physiology, Lange Medical Books, pp. 227, 2005). In contrast, there is no report disclosing that the cutaneous arteries are controlled by parasympathetic nerves. Thus, if the sympathetic nerve activity that controls a cutaneous artery is reduced, the cutaneous blood vessel is expanded so that blood flow increases. The results obtained in Experimental Examples 1 and 2 exactly reflect this biological reaction. More specifically, the results show that Litsea is capable of reducing cutaneous sympathetic nerve activity and, thus, has blood flow-increasing (blood circulation-promoting) effects. It is considered that the moisturizing effects of Litsea demonstrated in Experiment Example 1 were achieved because increased blood flow increased the supply of oxygen and nutrients to skin cells.
Embodiments of external preparations for skin of the present invention are described below. The lipid-soluble fraction of Litsea leaves obtained in Experimental Example 2 was used as the “processed product of a plant of the genus Litsea”.
Number | Date | Country | Kind |
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2007-297334 | Nov 2007 | JP | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/JP08/71064 | 11/13/2008 | WO | 00 | 5/14/2010 |