JPH08169839A - Non-irritant and non-metal-corrosive aromatic neutral resin oil extracted from evergreen shrub of cypress or hiba arborvitae family, and wound-curative agent and epithelialization promoter, medical auxiliary, surface activity promoter, and miteproofing and antimicrobial material containing the same as main component - Google Patents

Abstract

PURPOSE: To obtain the subject non-irritant and non-metal-corrosive resin oil by extraction, from HINOKI (Chamaecyparis Spach) as an evergreen shrub by removing tar and acidic components, and to obtain a wound curative agent and epithelialization promoter each containing this resin oil. CONSTITUTION: This aromatic neutral resin oil is obtained by extracting the trunks, leaves, wood chips, etc., of evergreen shrubs of Thujopsis dolabrata Sieb. et Zucc (ASUNARO) or Chamaecyparis Spach (HINOKI) family as a raw material through steam distillation. To remove tar component and acidic component such as thujaplicin, an alkali solution (e.g. of NaOH) is added to the extraction system followed by heating and agitation. This resin oil which is non-irritant and noncorrosive to metals has body temperature holding and humectant effect and blood circulation-improving action, has wound-curative and epithelialization promotive action as well as antibacterial and miteproofing effect.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to Cupressa (Cupressa).
Ceae) Resin neutral oils extracted from evergreen shrubs that are not corrosive or irritating to metal, and wound healing agents with antibacterial properties and aromatic neutral resin oils that promote epithelial formation The present invention relates to agents, medical auxiliary products, surface-active agents, anti-mitic and antibacterial materials.

[0002]

2. Description of the Related Art The evergreen shrubs of the cypress family have strong aroma and have characteristic aroma and stimulative properties in each genus, while the extracted resin oil contains tempels and tsuyapurisin. Taxonomy, Kiyohiko Watanabe, Kazama Shobo, 1976), and in particular, the antibacterial and bactericidal effects of tsuyaprisin are known, and the technology utilizing the effects is also known (Japanese Patent Publication No. 33-8518). In addition, natural disinfectant and bactericide (Japanese Patent Publication No. 02-3
2241), rot disease control agent (Japanese Patent Publication No. 02-32242), white crotch feather control agent (Japanese Patent Publication No. 02-32243), purple crest feather disease control agent (Japanese Patent Publication No. 02-32244), etc. Yes, it has been used as a bactericidal insecticide derived from natural products. As a method for purifying such tsuyapurisin (hinokitiol), a method of separating and purifying as a crystal of alkali hinokitiolate is disclosed in Pharmaceutical Journal (64: 181-185, 1944) by reacting tsuyapurisin-containing vegetable oil with alkali such as caustic soda. It is also known, but the conventional extraction method was mainly aimed at separating and purifying tsuyapurisin from Taiwan cypress and so-called Aomori Hiba. Also, for the purpose of utilizing the unique aroma of the evergreen shrub of the Cypress family, so-called cypress, small pieces of Hiba wood, sawdust is also disclosed as a method of immersing it in a bathtub as a cloth bag (Japanese Patent Laid-Open No. 5-112444). However, it is often described and registered incorrectly as a plant taxonomy. In addition, acid substances such as alkali and hinokitiolate are removed from resin oil extracted from so-called Hiba, which is considered to be Hinoki asunaro of the genus Asunaro, which is one of the genus of evergreen shrubs of the Cypressaceae family. A scented cleaning agent using a resin oil obtained by fractional distillation through an organic solvent such as ether has been disclosed (Japanese Patent Publication No. 02-26679). Conventionally, the utilization status of oil content collected from so-called Hiba cypress asnaro is mainly focused on the antiseptic action and antibacterial action of tsuyapurisin contained in the oil, and the residual waste oil of by-product when tsuyapurisin is extracted is It is highly stimulating.

[0003] However, even though the cypress family evergreen shrub has a scent, each genus species has a specific odor, and depending on the extraction method, unpleasant irritating components are mixed in. Is. On the other hand, providing a comfortable and hygienic living space to humans in a state close to the natural environment is strongly desired in the present situation where the advancement of social civilization and the arrival of an aging society are expected. Therefore, it provides an aroma and a hygienic living space that bring comfort to humans without stimulating the human special sensation (olfactory, visual, etc.) system and pain sensation widely distributed on the skin, etc. When the skin that is in contact with the external environment has skin defects such as trauma, burns, and pressure sores, bacterial infection is also likely to occur,
Although improvement of skin defects and antibacterial treatment are strongly expected, few of them are derived from natural products and have the above-mentioned effects, and their proposal is extremely important.

In the present invention, it is inferred from the historical process that the common names such as cypress and hiba transform the contribution of human beings from the natural world to the human being, such as industrial activities, and their exact significance. For the scientific future industrial development utilizing natural resources from the natural world, the plant classification names in the present invention are as follows (Japanese Botanical Journal (Kaika Hen) Oi Jisaburo, Shibundou, 1972). According to the cypress family (Cupressa
ceae) genus of cypress such as evergreen shrub (Chamaecyparis Spach),
It was described as Asunaro (Thujopsis Sieb. Et Zucc.).
Cypress (Hinoki Chameacyparis obtusa, Sawala Cha
(Maecyparis pisifera etc.) is a tree that has been planted and nurtured and preserved since ancient times, and this lumber of the cypress genus has long been used in Japan as an expensive building material, food storage, bathtub, etc. No specific studies have been conducted on the wound healing and epithelial formation promoting effects of resin oils of the cypress family, which are widely clustered in Japan, and have bactericidal and acaricidal effects, as well as warm bath effects such as heat retention, skin moisturizing effects, and aromaticity. No specific and unified study has been conducted on the effects of substances contained in and on the comfort of humans (including the effect of improving physiological functions) and the effect of promoting health. Furthermore, even if you try to use resin oil of evergreen shrubs such as cypress, Asunaro etc. as an antibacterial agent, acaricide, bactericidal disinfectant, of course, metal appliances using strongly acidic components such as Tsuyapurisin that shows strong acidity, There is a serious drawback that not only the metal that is sterilized (for example, furniture, medical devices, bathrooms, and other metals) is corroded, but also the nascent and regenerative effects of epithelial cells of the skin tissue of the living body are adversely affected. .

[0005]

Therefore, the present invention has been made to solve the above-mentioned problems, and an object of the present invention is to solve the problem of metal corrosion among resin oils extracted from resin oil of evergreen shrubs of the cypress family. The purpose is to use aromatic neutral resin oils that are not irritating or irritating. Another object of the present invention is to provide a wound healing and epithelialization-promoting agent containing an aromatic neutral resin oil as a main component and also having an antibacterial and antiseptic effect. In addition, when this aromatic neutral resin oil is used as a hot bath, cream or ointment, it has the effect of improving physiological functions such as heat retention and moisturizing properties, providing an excellent feeling of comfort as well as human living space. It is characterized in that there is no drawback that it corrodes metal equipment used in bathrooms and kitchens and medical equipment that requires sterilization.

[0006]

[Means for Solving the Problems] As a result of intensive studies conducted by the present inventors on the above problems, the tar content of evergreen shrubs of the cypress family (commonly not limited to cypress) and the acidity of tsuyapurisin, etc. It has been found that the neutral oil component from which the components have been removed achieves the above object, and the present invention has been completed.

The present invention will be described in detail below. Non-irritating and non-irritating and neutral aromatic resin oils according to the present invention include, for example, a tree component of a generic name Kiso cypress which is a typical name tree of the Japanese cypress family evergreen shrub in Japan. It is obtained by placing a raw material such as wood chips such as sawdust on a steel pressure cooker for generation and a copper mesh through which steam passes, and extracting by a known direct steam distillation method. This aromatic neutral resin oil is chemically neutral in nature, but when using tree components (branches, knots) with a large amount of acidic components such as tsuyapurisin and tree components of the genus Asunaro such as Aomori Hiba, they are directly steam distilled. Or, in order to further remove the residual acidic components after dry distillation, add a small amount of alkaline solution and heat to remove the acidic substances contained in the resin components such as tsuyapurisin and have non-irritating and aromatic properties. Obtain a resin oil.

When it is used as a cream or a hot bath, it has a heat retaining effect and a moisturizing effect. Especially, in the hot bath, a neutral oil component containing a natural non-irritating aromatic component causes a problem when taking a bath. It has the effect of improving physiological functions and has no metal corrosiveness. When these are used not only by healthy people but also by people with wounds and people with wound infections, they have bactericidal action, wound healing, and epithelial formation promoting action. This bactericidal action is not limited to indigenous bacteria such as Escherichia coli, Staphylococcus aureus, and Streptococcus, but also drug-acquired bacteria (for example, methicillin-resistant Staphylococcus aureus (hereinafter referred to as M
It also has an effect on acid-fast bacilli, Pseudomonas aeruginosa and fungi.

When the neutral resin oil of the present invention is used as a wound healing agent, an epithelialization promoting agent, a disinfectant bactericidal / anti-mite agent or a hot bath agent, the neutral resin oil such as cypress trees should be hydrophilic. You can also For example, alcohols, fatty acid esters, soap solutions, cyclodextrin, chitosan, surfactants, emulsifiers, wetting agents, foaming agents and the like, respectively.

In the method of using the neutral resin oil of the present invention as a wound healing, epithelialization-promoting agent, antibacterial / bactericidal agent or hot bath agent, a neutral resin oil such as cypress trees is adsorbed on an appropriate one to form a rod shape. It may be molded into a granular shape, a powder shape, a sheet shape, a capsule shape or the like, or may be solid. For example, gelatin, pullulan, sugar, porous starch, pregelatinized starch,
Soluble substances such as detergents, wood chips, sawdust, charcoal, building materials, natural and synthetic fibers, polymer synthetic membranes, sheets, and films.

The neutral resin oil of the present invention can be directly applied to the surface of a wound such as a burn, a pressure sore or an infected wound, or can be used in combination with a pharmaceutically acceptable carrier. Examples of the pharmaceutically acceptable carrier include polyoxyalkylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, polyvinylpyrrolidone, hydrocarbon, paraffin, alcohol, polyhydric alcohol, alcohol ester, polyhydric alcohol ester, fatty acid or Included are biologically acceptable carriers such as metal salts of fatty acids.

When the neutral resin oil of the present invention is used in combination with a pharmaceutically acceptable carrier, it has a generally known dosage form,
For example, creams, ointments, plasters, poultices, emulsions, suspensions, linitomen, lotions, aerosols, liquids and tapes can be used in various forms depending on the treatment form. A solubilizing agent, a tonicity agent, a pH adjusting agent, a deodorant, a preservative or a flavoring agent may be added.

The neutral resin oil of the present invention is infused or surface-treated not only with trees that grow in forests that are affected by core rot caused by decay fungi but also as raw materials for building materials, furniture, furniture and household products. By doing so, it is possible to obtain antibacterial, antibacterial, antifungal and insect repellent effects such as termites. Further, as a resin wax for home electric appliances, daily necessities, household articles, etc., from the environmental hygiene perspective, it can be expected to be effective in preventing slime of paper, pulp, etc., and in waste disposal.

The neutral resin oil of the present invention is a surface active agent for converting physical properties such as foaming, wetting, reduction of surface tension, emulsification (formation of emulsion), solubilization, formation of micelles and detergency of a surfactant. It can also be used as a promoter. The activator molecule is generally in the form of a long and thin rod, and is characterized in that one end has an affinity for water molecules and the other end has a property of keeping water molecules away. This feature occurs because surface tension works. The degree of surface activity is related to the critical micelle formation concentration, solubilization, Kraft point, and the like. The shorter the chain (rod) portion of the active agent molecule, the lower the Kraft point and the larger the value of the critical micelle formation concentration. Therefore, rather than making a detergent with only one type of molecule, mixing the molecules of various lengths gives a greater surfactant effect. When the aromatic neutral oil of the present invention is mixed with soap, detergent, shampoo, etc., the length of each activator molecule is different, so that the effect of the surface activity becomes larger than that of the non-mixed ones.

When the neutral resin oil of the present invention is mixed with an anionic, cationic, or nonionic surfactant, antibacterial and antifungal effects are obtained, and it is neutral and hard and water resistant. It has an excellent effect of promoting epithelial formation, and also has a hair-growth effect for hairy parts of the body, especially for hair. Therefore, it can be added to cosmetics such as cleansing cream, shampoo, conditioner, hair conditioner, hair restorer and the like. Other than that, antistatic agents for fibers and plastics, softening agents for fibers, foaming agents for aerosols, dyeing aids, household (tableware, furniture, household appliances, bath lavatory products, toilet bowls, kitchen) detergents, vehicle detergents. It can be used for

As described above, the non-irritating aromatic neutral resin oil extracted from evergreen shrubs such as cypress trees of the present invention is used for healing of wounds and infectious wounds and epithelium formation caused physically and chemically. It promotes (including hair-growth and hair-growth effects), has a pleasant fragrance without irritating odor in human olfactory sensation test, and has antibacterial, antifungal, bactericidal and disinfectant properties as well as anti-mitic effect. Furthermore, it has heat retention and moisture retention, and no metal corrosiveness is observed. In addition, an effective surface active state can be obtained.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION Next, the present invention will be described in detail with reference to the embodiments of the present invention, but the present invention is not limited thereto.

1 L of distilled water was placed in a pressure cooker, and a copper 5 cm mesh layer was worked on top of it so that water vapor could pass through (this is a device to make the electron transfer state in water vapor effective). The transition metal used for this is F
e, Ni, Co, Cu, Ti, etc., but not limited to these), dried cypress cypress cypress (produced in Kisoyama system, Nagano Prefecture) on the upper part of its copper mesh stem material (100 years old) -300 years old sawdust 250g
And put the lid on the pressure cooker. The lid of the pressure cooker has a small hole with a diameter of about 1 millimeter so that water vapor can flow out through the sawdust layer. Distilled steam from the small holes is put into Kolben of about 1 liter, and saturated distilled steam in Kolben is cooled and condensed through a cooling pipe to obtain a distillate. At this time, the distillate is separated into a lower water layer component and an upper oil layer component (average 5-6 milliliters). The oil component of this upper layer has an average pH of 7.1.
Is. It is also one of the features of the present invention that there is no need to extract the distillate using an organic solvent such as petroleum ether, and thus there is little adverse effect on the human body that may be caused by organic compounds and reaction products thereof. .

When the trunk, leaves, branches, etc. of cypress trees are mixed and the Asunaro tree, which has a large amount of acidic oil component, is used as a raw material, the crude resin oil obtained by the above method is acidic (pH
4.5-5.5), it is possible to add 5-10 milliliters of 0.1N sodium hydroxide solution to 100 milliliters of crude resin oil and stir with heating to remove acidic substances such as tsuyapurisin. Leave it in the water layer.

The above-mentioned cypress family cypress
Gas chromatographic method on cypress neutral oil obtained by steam distillation from Aris obutusa) (Model: Shimadzu G
C-3BF type chromatograph, measurement condition: used column O
V-17, inner diameter 3 mm, 5% SP-1200 +
1.75% Bentone 34 On, Chrom
osorb W. Then, after holding for 1 minute at the infusion temperature of 270 ° C. and the column oven temperature of 50 ° C., the content components were examined under the condition of heating at 5 ° C./minute to 260 ° C. and holding, as shown in FIG. The characteristic that there was no peak rising within minutes and 30 minutes or more was observed. Two
The component ratio of the peak rising within 30 minutes from the minute differs depending on the raw material (age, tree species, etc.).

<Minimum Sensitive Concentration of Aroma and Sensory Response Test> Healthy human adult (18-47 years old, same number of men and women) 2
About the minimum sensitivity test in suspended water and the sensation of aroma, 0 people gave hinoki neutral oil and Asunaro hinoki asunaro (T
hujopsis dolabtata) and a neutral oil extracted from it. As a result, the minimum sensitive concentration of cypress neutral oil is 1/1
It was 5,000, none complained of discomfort or irritation, and 90% answered "hinoki" scent. On the other hand, according to a known method such as Japanese Patent Publication No. 02-26679,
The minimum amount of neutral oil obtained by removing alkaline substances and hinokitiolates and other acidic substances from resin oil extracted from Asunaro hinoki asunaro, washing residual residual oil with water, and distilling water Sensitive density is 1 / 25,00
It was 0, 25% complained of discomfort, 65% complained of irritating odor, 30% complained of burnt odor, and 0% answered "hiba" scent. From these results, it was found that the cypress neutral oil is a non-irritating aromatic neutral oil that does not cause discomfort. Therefore, by appropriately diluting it, it can be used as a scent of cypress.

<Wound healing and epithelialization> After anesthetizing a white rabbit, a circular full-thickness skin defect with a diameter of 10 millimeters was created on the back and hinoki neutral oil (50 microliters) was added together with the target group. Each skin defect was treated every other day, and changes in the area of the skin defect were examined. As a result, when treated with cypress neutral oil, the area of the skin defect part was reduced by 65% compared to the control group one week after the operation (see Fig. 2), and the boundary with normal skin was clear by macroscopic observation. The epithelial formation was restored to such an extent. 3 (a) and 3 (b) show respective tissue specimen images. Further, after making a similar skin defect, 0.2 milliliter of concentrated hydrochloric acid was added to the skin defect to make a chemical burn. When treated with cypress neutral oil, the area of the skin defect portion was reduced by 50% one week after the operation compared with the control group (see FIG. 2). Furthermore, after creating a similar skin defect, fecal fluid was applied to the skin defect to create a natural infection wound model of the wound. When treated with cypress neutral oil, the area of the skin defect portion was reduced by 20% one week after the operation compared with the control group (see FIG. 2). Observation of each skin defect with an optical microscope revealed that the wound surface in the target group was irregularly swelled due to abnormal granulation tissue formation, and no epithelial formation was observed on the surface of the skin defect center, indicating an inflammatory reaction. The infiltration of neutrophils appearing in the mouse was remarkable. On the other hand, in the group treated with cypress neutral oil, abnormal granulation tissue formation was not observed, neutrophil infiltration was small, and epithelial formation on the wound surface was good. The effect of neutral oil from hinoki asunaro was that the neutrophil infiltration was suppressed as in the case of hinoki neutral oil, but the area of skin defect and the degree of epithelial formation were poor. This result shows that neutral oils of cypress family resin (especially cypress family resin) have effective repairing and epithelialization-promoting effects on physical and chemical skin damage and contaminated wounds. It has been shown to be effective against intractable skin damage.

<About antibacterial and bactericidal action> Using 5 Mesillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Trichophyton, which were taken from a septic patient and subcultured, the antibacterial action of cypress neutral oil at 5 microliters was confirmed. When the disc method was used to examine ordinary agar, BHI medium and Sabouraud medium, a sufficient size of inhibition circle was confirmed after 24 hours for each bacterium. The number of grown colonies (CFU) was measured after culturing for 24 hours at 37 ° C. with 10 ⁶ bacteria in each strain. MRSA in untreated group
CFU of 6 was grown to 10 ⁷ after 6 hours and 10 ¹⁰ after being cultured for 24 hours, but the number of bacteria was reduced to 10 ³ by treatment with 1 microliter of the culture solution of cypress neutral oil 5 microliters. After further culturing for 24 hours, CFU was zero (FIG. 4).
reference). In addition, in the treatment of MRSA with 1 milliliter of culture medium and 10 microliters of cypress neutral oil, CFU was zero 6 hours after the culture. Inhibition of growth of other bacterial species was observed in a volume-dependent inhibitory effect in the range of 1-50 microliters, and the minimum inhibitory concentration after 24 hours of culture was M
5 microliters of cypress neutral oil for 1 milliliter of culture medium for RSA, 4 microliters of cypress neutral oil for culture medium of 1 milliliter for Escherichia coli, and 1 milliliter culture medium of tinea The cypress neutral oil was 3 microliters. From these results, it was revealed that the neutral oil of the cypress family resin of the present invention has an antibacterial and bactericidal action against at least Gram-negative bacteria, Gram-positive bacteria and fungi.

Further, an antibacterial action was recognized against acid-fast bacilli and Pseudomonas aeruginosa at a minimum inhibitory concentration of 5 microliters of hinoki neutral oil in a culture of 1 milliliter. Attaching 20 microliters of cypress neutral oil to the surface of a 1 x 1 cm piece of building material (plywood or plastic) or fiber (acrylic or polyester), forming an inhibition circle on the agar medium of each pathogen. When observed, the formation of a remarkable inhibition circle was observed.

<About the antibacterial action of the vaporizing component> Mesicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Trichophyton, taken from a patient with sepsis and subcultured, were used to extract 50-100 microliters of hinoki neutral oil. The antibacterial action at the concentration was examined by the disc method using ordinary agar, BHI medium and Sabouraud medium. A filter paper disc in which the sample was dipped was placed on the bottom of the petri dish, and the medium in which each bacterium was inoculated was used as the ceiling of the petri dish so that the sample did not come into contact with the medium, and the growth state of each bacterium after 24 hours was observed.
As a result, no bacterial growth was observed at a concentration of 200 microliters. This result shows that the volatile components of cypress neutral oil also have an antibacterial effect.

<On turbidity in the bathtub and bacterial growth> Using the bath water of three healthy families who are engaged in daily life after bathing, we examined the growth inhibitory effect of pathogenic bacteria on ordinary agar and BHI agar medium. As a result, cypress neutral oil significantly inhibited the growth of pathogenic bacteria in a concentration-dependent manner, and the hot and cold water in the bathtub did not become turbid for 5 days or longer, and no precipitate was observed. Moreover, the effect of hinoki asunaro neutral oil was almost the same as that of hinoki neutral oil, but comfort was not recognized due to its strong aroma. This result is based on the bathing conditions used by many unspecified people, the high humidity environment,
For reuse and effective use of water resources, the cypress family resin of the present invention (particularly the cypress family resin) neutral oil is not accompanied by an unpleasant sensation due to aroma, and rather produces a pleasant scent of cypress
It was found that a sterilizing effect can be realized.

<About heat retention and moisturizing effect> Room temperature 2
In a small room kept at 2 ° C ± 2 ° C and 50% humidity, the forearms of five adult subjects (19 to 21 years old) were put on hinoki cypress neutral oil 10 ^-3.
And hot water (41-42 ° C) with a concentration of 10 ^-4 for 5 minutes, the skin temperature and skin hemodynamics before and after that were measured with hot water without addition of cypress neutral oil.
The temperature retention condition and blood circulation improvement condition were measured by ICS Inc. TUS2000), and the moisture retention condition was measured by the skin impedance method. As a result, the skin temperature was significantly elevated in the hot water containing hinoki cypress neutral oil at a concentration of 10 ^-3 and 10 ^-4 even after 2 hours from the loading, but in the hot water without the additive, After loading 1
After 5 minutes, the condition was restored to the state before the load (see FIG. 5, FIG. 5 is a graph in which the digitized temperature display was digitized from the thermographic photograph of the subject's forearm). Skin blood flow also increased over 30 minutes (see Figure 6). This result shows that the cypress neutral oil of the present invention has a heat retaining effect and a peripheral circulation improving effect. Moreover, the skin impedance was significantly increased over 1 hour or more (see FIG. 7). Moreover, the effect of the hinoki asunaro neutral oil was almost the same as that of the hinoki neutral oil, but many people (3 people, 60%) complained of discomfort to the test subjects due to the strongly irritating aroma. The results show that the cypress family resin (particularly cypress family resin) neutral oil has a heat retaining effect and a moisturizing effect without causing discomfort.

<Regarding the anti-mite effect> The mite mite and the mite mite were placed in a petri dish and the running state of each mite was observed by video shooting (13 times magnification) without the lid. In the state where cypress neutral oil was not attached, each mite moved irregularly in the petri dish and had a moving speed of 0.5-1.5 millimeters per second.
Diameters of the cypress neutral oil soaked in concentrations of 0 ^-3 and 10 ^-5 .
Immediately after placing the 8-millimeter circular filter paper on the petri dish, the mites began to escape from the filter paper in the centrifugal direction, and at a concentration of 10 ^-3 , the running speed was as fast as 2.8-3.7 millimeters / second, and about 1. After 2 hours, the presence of mites was not confirmed around the filter paper, and a valley ring was formed at a position about 3 cm away from the filter paper (see FIG. 8). This result indicates that cypress neutral oil has an anti-mite effect.

<Effects on Blood Pressure, Heart Rate, Capillary Diameter, and Sympathetic Nerve Activity> Blood pressure, heart rate, capillary diameter, and renal sympathetic nerve activity were measured using hybrid dogs under artificial anesthesia under anesthesia. . The cypress neutral oil was sprayed on the nasal mucosa of dogs. Blood pressure, heart rate, and renal sympathetic nerve activity are general electrophysiological methods. Furthermore, the capillary diameter is video-recorded under the in-vivo microscope (Nihon Kohden, Macroscope IVY 1100) to record the changes in mesenteric capillaries. Blood vessel (100-
The diameter and the blood flow velocity of 150 micrometers) were observed.
As a result, the systolic pressure was increased for 3 minutes after spraying on the nasal mucosa, the diastolic pressure was significantly decreased about 15 minutes after spraying, and the pulse pressure was also increased (see FIG. 9).
There was no significant difference in heart rate (see FIG. 10), and sympathetic nerve activity was reduced (see FIG. 11). Furthermore, the capillaries in the mesentery have a higher flow velocity than 2-3 minutes after spraying,
It continued even after a minute (see FIG. 12). In addition, the effect of cypress asunaro neutral oil was less likely to show a certain reaction than cypress neutral oil, and an unstable physiological reaction appeared. These results show that olfactory stimulation of the hinoki cypress neutral oil of the present invention causes vasodilation and has a stable olfactory stimulating effect as compared with the hinoki asunaro neutral oil.

<Non-Metal Corrosion> No metal corrosion was observed even after immersing a 2 × 5 millimeter iron piece in cypress neutral oil for 1 week or longer, and in a 1% tsuyapurisin solution as a target reagent. Oxidized iron pieces were observed after 1 day, and the degree of oxidation increased with the passage of days. This result indicates that cypress neutral oil does not have metal corrosiveness.

<Regarding the Effect of Promoting Surfactant Activity> 10 microliters of hinoki neutral oil was added to 10 milliliters of a kitchen detergent containing a fatty acid alkanolamide as a surfactant, with or without addition of animal oils. Comparing the cleaning effect of tableware soiled with, when adding cypress neutral oil, there was no sticky feeling, fine foaming occurred, good drainage, and more effective action as a cleaning agent. It was Furthermore, the surfactant is composed of sodium alkyl ether sulfate, fatty acid alkanolamide, polyoxyethylene alkyl ether, and the like, and a commercially available kitchen detergent (trade name Charming, Lion Co., Ltd .: trade name Natella, Lion Co., Ltd .: Product name Moa, Kao Co., Ltd., lauryl sulphate, paraben, cetanol, edetate, propylene glycol, polyoxyethylene lauryl ether sulphate, etc. for shampooing hair (trade name Pantene, Max Factor Inc.): The effect was examined by adding 50 microliters of cypress neutral oil to 20 milliliters of each of product name Lux Styling, Nippon Reaver Co., Ltd .: Product name Essential Styling, Kao Co., Ltd.). Each of the added detergents and shampoos had better foaming, fine bubbles, and oily stains could be easily washed with water, and an extremely small amount of water was sufficient for washing. By the addition, no major change was observed in the appearance such as color tone and gloss of each detergent and shampoo,
Viscosity (Vismetron VEA-
L, manufactured by Shibaura System Co., Ltd., the values were higher than those without addition of any inspection data (see Table 1). Moreover, the relationship between shear rate and shear stress was also increased by the addition. This indicates that the effects such as the surface activity of detergents and shampoos can be improved by adding hinoki neutral oil to commercially available detergents and shampoos.

[Table 1]

<Functions of Polymer on Physical Properties> Physical properties of polymers (changes in gloss and gloss, accuracy of boundaries in template formation, surface smoothness and uniformity, transparency, fineness, quantity The effects of cypress neutral oil on the changes (eg changes) were confirmed. Each of the following substances (all purchased from Wako Pure Chemical Industries)
Add 100 microliters of cypress neutral oil per 10 grams, heat it until it dissolves in a water tank, pour each solution into a tooth filling model of caries for dental treatment, and cool it until it becomes solid. It was taken out from the mold and observed with a magnifying glass of 2-5 times. Octadecanol and stearic acid reduce the surface smoothness, fineness and transparency, and lauric acid shows the appearance of smoothness and transparency. Dodecanol (lauryl alcohol) is so soluble that it is difficult to maintain its shape at room temperature. increased. With palmitic acid, softness and smoothness appeared, and with myristic acid, the appearance of boundary sharpness, smoothness and uniformity was remarkable. Hexadecanol reduced the fineness and transparency. Polyethylene glycol 1000 improves boundary sharpness and smoothness, and polyethylene glycol 1540 also improves smoothness, uniformity, and transparency, while polyethylene glycol 2
000, polyethylene glycol 4000, the sharpness of the border is slightly worse.
At 00, an increasing tendency of gloss was recognized. In addition, N-isopropyl acrylamide (Wisconsin, USA,
(Manufactured by Aldrich Chemical Co.), gloss, boundary sharpness, surface uniformity, transparency and fineness were recognized. These results indicate that cypress neutral oil can improve the physical properties of polymers used for medical, household and industrial applications.

Next, the validity of macroscopic observation was determined by examining the results of microscopic observation of changes in the physical properties of each polymer. Changes in physical properties of the polymer were examined by a differential scanning calorimeter (DSC-50, manufactured by Shimadzu Corporation). The results with palmitic acid and polyethylene glycol 1000 are illustrated in FIG. When a neutral resin oil was added to palmitic acid, the melting point was lowered, and in the polyethylene glycol 1000, the endothermic reaction portion around 40 ° C disappeared, and the endothermic portion around 150 ° C moved to 120 ° C. This indicates that the thermodynamic properties have changed. Further, when the expandability of polyvinyl chloride was examined with a thermomechanical analyzer (TMA-50, manufactured by Shimadzu Corporation), no increase in volume was observed at around 310 ° C. (see FIG. 14).

[0034]

EXAMPLES The composition of the present invention will be specifically described with reference to examples of ointment formulations, but the present invention is not limited to these examples. The mixing ratio is% by weight.

Formulation Example 1 [Cream (vanishing type)] Cypress neutral oil (0.3), cetanol (8.5), stearic acid (10.0) solid paraffin (2.0), octyldodecyl mistynate (5.0), isopropyl myristate (5.0), glyceryl monooleate (0.
The oil phase components of 5) are weighed and mixed, and dissolved by heating at about 80 ° C. On the other hand, citric acid. Monohydrate (0.
5), the water phase components of distilled water (67.7) are weighed and mixed, and heated to about 80 ° C. While stirring the oil phase component, the water phase component is gradually added to this and emulsification is performed. If you gradually cool it with stirring, burnishing cream (O
/ W emulsion).

Formulation Example 2 [Ointment type] Tosufloxacin tosylate and 0.2 milliliter of cypress neutral oil are added to liquid paraffin and stirred. When this is added to Plastibase and thoroughly mixed with stirring, a hinoki neutral oil ointment (lipophilic ointment) is obtained.

Formulation Example 3 [Ointment type] 1 part of cetanol, stearyl alcohol, and vaseline.
A hinoki cypress neutral oil ointment (hand cream) is obtained by making 50 grams of cream in a weight ratio of 1: 5, adding 0.4 milliliters of cypress neutral oil to this, and thoroughly mixing with stirring.

Formulation Example 4 [Detergent type] 500 microliters of cypress neutral oil was added to 1 liter of a 30% surfactant (polyoxyethylene alkyl ether, sodium alkyl ether sulfate ester, fatty acid alkanolamide) solution. If you mix well with stirring, you can get a hinoki neutral oil detergent.

Example: When the above hand cream was subjected to the same treatment as a hand cream conventionally used once a day to a housewife with intractable cutaneous dysfunction on his hands, daily work as a housewife Even after doing it, he was completely cured one week later. Also,
A 47-year-old man who had refractory leukoplakia on his sole for more than 20 years healed after a week. In addition, steroids cannot be used in refractory atopic dermatitis 20
When used on an old man, the healing effect was noticed after 3 days,
It was objectively recognized. Also, 10x on the buttocks due to cerebrovascular disorder
72 with a refractory pressure sore that reached 8 cm of periosteum
When this ointment was used in a year-old man, an increase in fresh granulation in the ulcer area and a decrease in exudate due to infection were observed in one week, and the ulcer area was reduced (7 × 5 cm) in two weeks.
Was recognized. In addition, in the cases of males and females aged 18 to 47 years old, itching and redness immediately after being bitten by insects such as mosquitoes disappeared by applying this cream to the affected area. No side effects were observed in any of the above cases. In addition, in a 48-year-old man in whom hair loss of the forehead, so-called baldness, has progressed, a shampoo is prepared by adding 300 microliters of cypress neutral oil to 300 milliliters of commercially available shampoo that is regularly used daily. Hair shampooing with this new shampoo is carried out in the same manner as in the case where the patient has been washing hair before taking a bath (about 3
-5 milliliters / once) was carried out for one month, a large number of soft and thin hairs of 1-2 millimeters were observed in the hair loss portion, and after two months, each hair that grew was long. The thickness also increased, and a reduction in the hair loss part on the appearance was observed (see FIG. 15). Thus, not only the effect of promoting epithelial formation but also the effect of increasing hair growth can be obtained by the simple method of shampoo for washing hair as in this example.

(Medical-physiological concept of comfort (physiological function improving effect) and significance of the present invention) Various protective functions exist in the living body. Above all, the functions of the nervous system and endocrine system are the same as those of the immune system. It is an important physiological regulation mechanism along with the function. The elucidation of the functions of the autonomic nervous system, endocrine system, and immune system among the defense function systems of these living bodies is a long history of medical research including physiology. Therefore, many research results have been accumulated in this field, and the functional regulation (endocrine system, autonomic nervous system) that operates in the human body unconsciously in daily life has been elucidated. (Reference: Koyama, Hypotension-Pathophysiology for Clinicians-
Fujita Publishing Project, 1994). The "comfort level" of the living body shows a complex aspect due to unconscious function control of the endocrine system and autonomic nervous system. In Japan, since it has been used for living spaces (building materials, bathtubs, etc.) since ancient times, and is still highly valuable, by using a non-irritating aromatic neutral resin oil extracted from natural cypress (Kiso cypress), etc. Not only when humans are in a medically morbid state (for example, stress, infection, trauma, etc.), but also from the scientific thinking aimed at improving the quality of life space in healthy humans. It is considered that the significance of the present invention in terms of the relationship between human beings and nature is significant in terms of the history of ecological civilization and the history of scientific methodologies of the present invention, and the significance of the present invention is described here.

[Brief description of drawings]

FIG. 1 is a non-irritating and non-corrosive aromatic neutral resin oil extracted from evergreen shrubs of the genus Cypress or Asunaro according to the present invention, which is one embodiment of cypress neutral oil. It is a gas-chromatographic-analysis figure of.

FIG. 2 is a graph showing the results of wound healing of the cypress neutral oil of FIG.

3 (a) and 3 (b) are tissue specimen images showing the state of wound healing epithelial formation of the cypress neutral oil of FIG. 1, respectively.

FIG. 4 is a diagram showing the antibacterial action of the cypress neutral oil of FIG. 1 on MRSA.

FIG. 5 is a diagram showing a heat retaining effect of the cypress neutral oil of FIG. 1.

FIG. 6 is a diagram showing the blood circulation promoting effect of the cypress neutral oil of FIG. 1.

FIG. 7 is a view showing a moisturizing effect of the cypress neutral oil of FIG. 1.

8 (a) and 8 (b) are diagrams showing the anti-mite effect of the cypress neutral oil of FIG. 1, respectively.

FIG. 9 is a diagram showing the effect of the hinoki cypress neutral oil of FIG. 1 on blood pressure.

FIG. 10 is a graph showing the effect of the cypress neutral oil of FIG. 1 on heart rate.

FIG. 11 is a graph showing the effect of the cypress neutral oil of FIG. 1 on sympathetic nerves.

FIG. 12 is a diagram showing the effect of the cypress neutral oil of FIG. 1 on the capillary diameter.

FIG. 13 is a chemical substance (paltimic acid and polyethylene glycol 10 added with the cypress neutral oil of FIG. 1).
It is the figure which showed the measurement result of the heat quantity change of (00).

FIG. 14 is a diagram showing the measurement results of the volume change of the polymer (polyvinyl chloride) to which the cypress neutral oil of FIG. 1 is added.

FIG. 15 is a view showing a hair-growing effect by the shampoo to which the cypress neutral oil of FIG. 1 is added.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI Technical indication location A61K 7/02 A 7/06 7/50 C11B 9/00 Z (54) [Title of invention] Hinoki Aromatic neutral resin oil extracted from evergreen shrubs of the genus or Asunaro and not having metal corrosiveness, and a wound healing agent and an epithelialization promoter containing the aromatic neutral resin oil as a main component, Medical aids, surfactants, mites and antibacterial materials

Claims (7)

[Claims] 1. A non-irritating, non-corrosive aromatic medium extracted from an evergreen shrub of the genus Hinoki or Asunaro, which is extracted from evergreen shrubs of the genus Hinoki or Asunaro excluding tar and acidic components. Resin oil. 2. A non-irritating aromatic neutral resin oil extracted from the evergreen shrub of the genus Cypress or Asunaro according to claim 1 extracted by a steam distillation method. 3. A non-irritating aromatic neutral resin oil extracted from the evergreen shrub of the genus Cypress or Asunaro according to claim 2, which does not use any organic solvent in the fractionation process. . 4. A non-irritating and metal extracted from the evergreen shrub of the genus Hinoki or Asunaro according to claim 1, obtained by adding an alkaline solution to a vegetable oil containing an acidic substance such as tsuyaprisin and heating and stirring the mixture. Aromatic neutral resin oil that is not corrosive. 5. A wound healing agent and an epithelialization-promoting agent prepared by mixing the aromatic neutral resin oil according to any one of claims 1 to 4 with a pharmaceutically acceptable carrier. 6. A medical auxiliary product or a surface-active promoter containing or added to the aromatic neutral resin oil according to any one of claims 1 to 4. 7. An anti-mite and antibacterial material containing or added to the aromatic neutral resin oil according to any one of claims 1 to 4.