JPH038781B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Application Field> The present invention relates to a menthol-containing mask useful for preventing and improving combing, nasal discharge, and nasal congestion caused by colds, rhinitis, allergies, and the like. <Conventional technology> Dry rash caused by cold, rhinitis, allergies, etc.
Pharmaceuticals for preventing and improving nasal discharge and congestion include antihistamines such as diphenhydramine, antipyretic/analgesic and antiinflammatory agents such as aspirin, and antiallergic agents such as diclofenac sodium, ketotifen, and tranilast. oral formulation,
It is administered in the form of injections, etc. However, these forms of administration generally exhibit their effects as systemic effects, and therefore are insufficient in terms of immediate efficacy, such as weak local improvement effects or a long time required for the effects to appear. Furthermore, it may be accompanied by side effects such as drowsiness and gastrointestinal ulcers, so a preparation that is immediately effective and free of side effects is expected. One way to improve this is by spraying an antiallergic agent such as diclofenac sodium into the nasal cavity in the form of an aqueous solution or suspension. This preparation is for administering the drug locally, ie, directly to an inflamed area such as the nasal mucosa. Therefore, compared to the above-mentioned oral preparations and injection preparations, it has a more immediate effect and can be expected to have a high improvement effect. However, since it is a liquid drug, when administered into the nose, the aqueous solution or suspension tends to flow out of the nasal cavity, the effect generally does not last long, and handling is troublesome, making it unsatisfactory as a preparation. It was hot. In addition, as another improvement measure, there is a mask with a drug-impregnated member, in which a drug-impregnated member such as menthol or camphor is inserted into the mask (Utility Model No. 55
-Refer to specification No. 40873). However, since this mask is simply a mask made of ordinary fibers impregnated with menthol, zero-order release of menthol does not occur, and as a result,
It was not possible to effectively treat cold symptoms. <Problems to be Solved by the Invention> As described above, in the prior art, formulations such as oral preparations and injection preparations have had problems such as taking time to develop their effects and being accompanied by side effects. Also,
Sprays such as aqueous solutions and suspensions have problems such as lack of long-lasting effects and cumbersome handling. In view of the problems of the prior art, the purpose of the present invention is to provide a method for preventing combing, nasal discharge, and nasal congestion that has immediate effect, is long-lasting, and is easy to handle.
and to provide a menthol-containing mask useful for improvement. <Means for Solving the Problems> The present inventors have developed a method for preventing combing, nasal discharge, and nasal congestion that has immediate effect, long-lasting effect, and is easy to handle.
and methods of improvement. As a result, menthol, which has pain and anti-pruritic effects and is used in topical preparations such as poultices and is also frequently used as a fragrance, has been found to be effective against sneezing, runny nose, and nasal discharge caused by colds, rhinitis, allergies, etc. It was also found to be effective against blockages. However, since menthol has the property of gradually sublimating at room temperature, only a temporary effect can be obtained with normal administration forms. Therefore, as a result of further intensive studies, the present inventors found that an immediate and sustained effect of menthol can be obtained by using a menthol-containing mask equipped with a menthol sustained release holder that vaporizes this menthol at a predetermined rate. The present invention was developed based on the knowledge that Accordingly, the present invention provides a fibrous material comprising microporous hollow fibers containing menthol in at least a portion of the mask, the menthol being vaporized at a rate of 0.2 to 10 mg/hour at about 30°C. This is a menthol-containing mask equipped with a menthol sustained release holder. In the present invention, a menthol sustained release holder is provided in the mask. This allows the vaporized menthol to be applied directly to the nasal mucosa, thereby providing immediate effect, which is one of the objectives of the present invention. In the present invention, it is important to supply a sufficient amount of menthol to improve the above-mentioned symptoms, so the evaporation rate of menthol is controlled and the
It is especially necessary to ensure that the gas is released at a vaporization rate of 0.2 to 10 mg/hour. Further, it is desirable that this vaporization rate be as constant as possible immediately after use of the mask and after use, and that it be sustained for one hour or more. In other words, the vaporization rate of menthol is about 30℃.
At doses below 0.2 mg/hour, there was a menthol scent, but it had little effect on improving symptoms such as combing, runny nose, and stuffy nose. On the other hand, the vaporization rate of menthol is 10
If it exceeds mg/hour, the stimulation becomes too strong,
Also, if you come into contact with menthol in this state for a long time, side effects such as fatigue will occur. Therefore, the preferred vaporization rate for a fast-acting menthol-containing mask varies somewhat depending on the severity of symptoms such as combing, nasal discharge, nasal congestion, etc., but the average value per hour is 0.2 to 10 mg, particularly 1 to 5 mg. is preferred. Further, if the above-mentioned vaporization rate was not sustained for more than one hour, or if a constant vaporization rate was not maintained over time, sufficient improvement of symptoms was not observed. In the menthol sustained release carrier of the present invention,
By controlling the material, surface area, thickness, etc. of the holder, it is possible to control the vaporization rate of menthol. Furthermore, in order to control the vaporization rate of menthol and maintain it for a long period of time, it is necessary to increase the amount of drug per unit area, and therefore it is desirable that the voids in the carrier are large. In addition, when the menthol sustained-release holder is attached to and removed from the mask, and when worn, it is constantly subjected to stress due to bending and stretching, so if menthol crystals are simply attached, they will fall off every time the mask is bent and stretched. This can seriously damage the image, and the powdered menthol that falls off can be inhaled when exhaled, causing major local irritation. Therefore, the fibrous material made of microporous hollow fibers of the present invention, such as a cotton-like material, or a sheet material such as cloth, paper, or nonwoven fabric containing menthol, can control the vaporization rate, Most preferred from the viewpoint of sustainability, ease of handling, etc. In other words, most of the menthol is contained in the hollow part of the hollow fibers, so menthol does not fall out at all under normal stress.
Furthermore, the amount of menthol that can be contained is large. A further advantage of using this hollow fiber is that the vaporization rate of menthol is almost zero-order release. In order for the vaporization of menthol to be a zero-order release, it is sufficient that the vaporization at the rate-determining stage is constant, but when menthol is contained in these hollow fibers, the actual menthol release surface is the surface of the hollow fibers. This is the total area obtained by multiplying the cross-sectional area of the through-hole opened by the number of holes in the through-hole, and it is not important how much menthol is filled in the hollow part.
To do this, put a volatile liquid in a beaker, cover the entire wide mouth of the beaker with a drug-impermeable film such as polyethylene, and check the amount of volatilization of the liquid by making a needle hole at one point in the polyethylene film. This is a result that can be expected from the test. However, the rate-limiting step of vaporization of menthol from a sustained-release carrier obtained by woven or knitted hollow fibers, folded or laminated fibrous materials, or coated with a menthol-impermeable membrane is In some cases, the surface area of the holding body is provided to allow menthol to escape from the sustained-release holding body, but even in this case, if the vaporization from such hollow fibers is zero-order release, then the Vaporization from a holding body is also a zero-order emission. The hollow fibers having holes penetrating in the outer circumferential direction used in the present invention are scattered over the entire surface of the hollow fibers,
Hollow fibers having micropores arranged in the fiber axis direction and at least some of which communicate with the hollow portion are preferred. Both the outer shape and the shape of the hollow portion in the cross section of the hollow fiber of the present invention may be arbitrary. For example, the outer shape and the hollow part may both be approximately circular, one of the outer shape and the hollow part may be approximately circular and the other irregularly shaped, or both the outer shape and the hollow part may have similar or dissimilar irregular shapes. . Further, there is no particular restriction on the size of the external shape. The hollowness ratio of the hollow fiber of the present invention may be arbitrary, but it is particularly preferably 5% or more, and the ratio of the holes penetrating in the outer circumferential direction to the cross-sectional area of the fiber is 0.001 of the cross-sectional area of the fiber excluding the hollow portion. ~70% is preferred, particularly 0.01~50%, and more preferably 1~50%. In the present invention, such hollow fibers may be used as long fibers, may be used rolled up like a ball, or may be cut into lengths of 5 to 1000 mm. In particular, when used in the form of a tissue such as a woven fabric, knitted fabric, or non-woven fabric, it is preferable because it provides good handling properties, a good feel on the skin, and an excellent sustained drug release effect. Among these, knitted fabrics are particularly preferred because they have high elasticity and cause less discomfort when applied to humans as a holder. The weight of knitting is 5~
2000 g/m ² , especially 10 to 1000 g/m ² is preferred. Materials for the hollow fibers used in the present invention include, for example, polyesters such as polyethylene terephthalate; polyolefins such as polyethylene and polypropylene; polyamides such as nylon 6 and nylon 66; polyurethane, cellulose acetate, polyacrylonitrile, polyvinyl chloride, and polyvinyl acetate. etc., you can choose anything you like. Among these, polyesters are preferred, and polyethylene terephthalate is particularly preferred from the viewpoint of good thermal stability, chemical stability, little interaction with drugs, and safety as a formulation. The hollow fiber used in the present invention is, for example,
-20612 Publication, JP-A-56-20613, JP-A-Sho
It can be produced by the method described in JP 56-43420 and the like. In the present invention, the above-described hollow fibers containing a drug in the hollow portions of the hollow fibers having holes penetrating in the outer circumferential direction are used. The drug may exist alone in the hollow portion, or may exist together with an adhesive described below, or may contain commonly used excipients, dissolution aids, diffusion aids, and absorption promoters. It may also be present together with other agents.
The drug can be loaded into the hollow portion of the hollow fiber by any method. For example, hollow fibers may be immersed in a solution containing a drug, then taken out and the solvent removed, or the drug may be mixed with excipients, solubilizing agents, diffusion aids, absorption enhancers, etc. and then dissolved in a solution. A method is used in which the hollow fibers are immersed in or brought into contact with the hollow fibers. Means such as heating, pressurization, vacuum depressurization, ultrasonic vibration, etc. can also be used to aid in the penetration of the drug or drug mixture into the hollow portion of the hollow fiber. In the present invention, a sustained release menthol holder containing such menthol is used by being attached to a mask. The size of commercially available masks is 9cm x
It is approximately 12 cm in length, and outside air is inhaled and exhaled air is exhausted from this area. If the holder is air-permeable, its size may be the same as that of the mask, or the mask itself may be the holder, but the purpose of the present invention is to control and sustain the vaporization rate of menthol. Above, the effective surface area of the holder when worn, that is, the area of both the front and back sides, excluding the area covered with a menthol-impermeable film to prevent menthol from vaporizing.
Preferably, it is 90 cm ² or less. That is, if menthol can be vaporized from both the front and back sides of the holder, the area of one side is 45 cm ² or less. The menthol sustained-release holder can be attached to a mask by sandwiching the holder between the gauze of a mask, which usually consists of several pieces of gauze or layered gauze, or by sewing it onto the mask. Although any other method can be used, if an adhesive layer is provided on a part or the entire surface of the holder, it can be attached to the mask very easily. Menthol easily permeates through a normal adhesive layer, so the location of the adhesive layer is simply a matter of prioritizing ease of attachment when attaching the holder to the mask and efficiency when producing the holder. Just think about it. In particular, the thinner the adhesive layer is, 30 μm or less, the more preferable it is because when the holder is attached to the mask and only the holder is removed from the mask after use, the adhesive does not stick to the mask, so-called adhesive residue. The menthol used in the present invention is preferably -menthol, but may also be dl-menthol. In addition to menthol, the sustained release menthol carrier of the present invention may contain fragrances such as vanillin and other components. The present invention will be explained in more detail with reference to Examples below. Parts in Examples and Reference Examples indicate parts by weight. Reference example 1 Preparation of hollow fiber sample 297 parts of dimethyl terephthalate, 265 parts of ethylene glycol, 53 parts of sodium 3,5-di(carbomethoxy)benzenesulfonate (11.7 mol% based on dimethyl terephthalate), manganese acetate 4 water 0.084 parts of salt and 1.22 parts of sodium acetate trihydrate were placed in a glass flask equipped with a rectifying column, and a transesterification reaction was carried out according to a conventional method. After the theoretical amount of methanol had been distilled out, the reaction product was placed in a glass flask equipped with a rectifying column. Add a 56% aqueous solution of orthophosphoric acid as a stabilizer to the condensation flask.
0.090 parts and antimony trioxide as polycondensation catalyst
Add 0.135 parts and heat to 30mm at 275℃ for 20 minutes under normal pressure.
The reaction was carried out for 15 minutes under reduced pressure of Hg. The resulting copolymer had an intrinsic viscosity of 0.405 and a softening point of 200°C. After the reaction was completed, the copolymerized polymer was made into chips according to a conventional method. 15 parts of chips and intrinsic viscosity of this copolymer
0.640 polyethylene terephthalate chips 85
After mixing for 5 minutes in a Nauta mixer (manufactured by Hosokawa Iron Works), the mixture was heated at 110°C for 2 hours in a nitrogen stream.
After further drying at 150℃ for 7 hours, the chips were melt-kneaded at 290℃ using a twin-screw extruder to form chips.The intrinsic viscosity of these chips was 0.520, and the softening point was 0.520.
It was 262℃. The chips are dried in a conventional manner and placed in a spinneret.
A circular slit of 0.05 mm and a diameter of 0.6 mm with two closed arcuate openings was used and spun according to a conventional method to obtain hollow fibers (hollow fibers) with a ratio of outer diameter to inner diameter of 2:1. rate of 25%). This raw yarn was 300 denier/24 filaments, and was drawn in a conventional manner at a draw ratio of 4.2 times to obtain a multifilament of 71 denier/24 filaments. This multifilament was knitted into a knitted fabric, and after being scoured and dried by a conventional method, it was treated with a 1% caustic soda aqueous solution at boiling temperature for 2 hours to achieve an alkali loss rate of 15%, a water absorption rate of 3 seconds, a water absorption rate of 82%, and a basis weight.
A fabric weighing 135 g/m ² was obtained. Incidentally, the water absorption rate and water absorption rate were measured by the following method. (a) Water absorption rate test method (according to JIS-L1018) The above-mentioned fabric was washed with a 0.3% aqueous solution of anionic detergent Zab (manufactured by Kao Soap Co., Ltd.) in a household electric washing machine for 40 minutes.
Wash the sample for 30 minutes at ℃ for 10 times, then dry it. Place the resulting sample horizontally and drop 1 drop (0.04 cc) of water from a height of 1 cm above the sample to ensure that the water is completely absorbed by the sample. Measure the time until reflected light is no longer observed. (b) Water absorption measurement method A sample obtained by drying a fabric is immersed in water for at least 30 minutes, and then dehydrated for 5 minutes in a dehydrator of a household electric washing machine. It was calculated from the weight of the dry sample and the weight of the sample after dehydration using the following formula. Water absorption rate = (sample weight after dehydration - dry sample weight) /
Dry sample weight (%) The hollow fibers obtained by the method described above are hollow fibers having micropores that are scattered over the entire surface of the hollow fibers and arranged in the fiber direction, and at least a part of which is in communication with the hollow part. It was hot. Reference Example 2 Creation of adhesive solution and adhesive layer 97.4 parts of 2-ethylhexyl acrylate, 2.5 parts of methacrylic acid, 0.1 part of polyethylene glycol (degree of polymerization 14) dimethacrylate, 1.0 part of benzoyl peroxide and 100 parts of ethyl acetate were cooled under reflux. vessel,
The mixture was placed in a reaction vessel equipped with a stirrer and polymerization was continued for 9 hours at 60°C under a nitrogen atmosphere with gentle stirring. The polymerization addition rate was 99.9%. 500 parts of ethyl acetate was added to the obtained polymer solution to adjust the solid content concentration to about 20% to obtain an adhesive solution. An ethyl acetate solution containing the adhesive was applied onto a silicone-coated release paper to a thickness of 20 μm in a dryer, and dried at 90° C. for 10 minutes to obtain an adhesive layer. Example 1 - 100 parts of a solution obtained by mixing 65 parts of menthol and 35 parts of acetone was added to the hollow fiber sample obtained in Reference Example 1.
After impregnation by dropping onto 100 parts, the acetone was removed by air drying to obtain a fabric containing 86 g/m ² of -menthol. This cloth was cut into circles with a diameter of 22 mm to obtain a menthol sustained release carrier containing 33 mg of menthol in one preparation. This holder was placed in a hot air dryer with a temperature controlled at 30°C, and the amount of menthol sublimated over time was examined. It lasted for a long time. When this holder was sewn into a mask and worn by a person suffering from nasal congestion due to a cold,
The stuffy nose went away after 20 minutes. Example 2 The adhesive layer obtained in Reference Example 2 was attached to one side of the circular sustained release menthol support with a diameter of 22 mm containing 33 mg of menthol obtained in Example 1, and the adhesive layer obtained in Reference Example 2 was further attached to the free surface of this adhesive layer. 6μ thick on the curved side
A polyethylene terephthalate film was attached, and an adhesive layer was attached to the free surface of the film. The sustained release menthol carrier obtained in this way is
- It has a structure in which a layer of hollow fiber cloth containing menthol, an adhesive layer, a film layer, and an adhesive layer are laminated in this order. When this holder was placed in a hot air dryer controlled at a temperature of 30°C and the amount of menthol sublimated was examined over time, it was found that - menthol sublimated at a nearly constant rate of 2.3 mg/hour over 14 hours. It lasted. This holder could be easily attached and detached into an ordinary mask using an adhesive layer. When this holder was attached to a mask and worn by a person suffering from nasal congestion due to a cold, the nasal congestion disappeared after about 60 minutes. This holder could be easily removed from the mask when not in use. Comparative Example 1 - 100 parts of a solution obtained by mixing 20 parts of menthol and 80 parts of acetone was added to the hollow fiber sample obtained in Reference Example 1.
After impregnation by dropping onto 100 parts, the acetone was removed by air drying to obtain a fabric containing 26 g/m ² of menthol. This cloth was cut into circles with a diameter of 40 mm to obtain sustained release menthol carriers each containing 33 mg of menthol. This holder was placed in a hot air dryer controlled at a temperature of 30°C, and the amount of sublimation of menthol was examined over time. - Menthol sublimated at a nearly constant rate of 16.1 mg/hour over a period of 2 hours. It was released. When the main holder was sewn into a mask and worn by a person, the irritation was too strong and the mask felt uncomfortable. Comparative Example 2 An adhesive layer was laminated by pressure bonding on the entire exposed surface of the menthol-containing hollow fiber cloth surface of the menthol sustained release support obtained in Example 2, and then the adhesive layer was laminated on the entire exposed surface of the hollow fiber cloth surface containing menthol. A 70 μm thick film made of ethylene-vinyl acetate copolymer was attached onto the free surface to obtain a menthol sustained release carrier. This holder was placed in a hot air dryer controlled at a temperature of 30°C, and the amount of sublimation of menthol was examined over time.The vaporization rate of menthol was 0.18.
mg/hour. This holder was attached to a mask and worn by a person suffering from nasal congestion due to a cold, but no improvement in nasal congestion was observed even after 2 hours. Comparative Example 3 0.5 g of ointment containing 5% menthol in white petrolatum was applied to a mask so that the area had a diameter of 22 mm, and the mask was placed in a hot air dryer controlled at a temperature of 30°C and dried over time. The amount of sublimation of menthol was investigated based on the remaining amount of menthol, and the results were as shown in Table 1.

[Table] In this test, masks coated with Vaseline could not be reused.

Claims (1)

[Scope of Claims] 1. At least a portion of the mask is a fibrous material made of microporous hollow fibers containing menthol, the menthol being heated to 0.2 to 10% at about 30°C.
A menthol-containing mask equipped with a menthol sustained release holder that vaporizes at a rate of mg/hour. 2 A fibrous material consisting of microporous hollow fibers is
The menthol-containing mask according to claim 1, which is a cotton-like material, or a sheet material such as cloth, paper, or nonwoven fabric. 3. The menthol-containing mask according to claim 2, wherein an adhesive layer is provided on one or both sides of the planar body. 4. The menthol-containing mask according to any one of claims 1 to 3, wherein the microporous hollow fibers are polyester hollow fibers.