JPH01221313A - Sublimation-releasable medicine composition and releasing system thereof - Google Patents

Abstract

PURPOSE:To provide a sublimation-releasable medicine composition suitable for being absorbed from the mucosa of a nose, by impregnating or coating a solid substrate with a physiologically active substance having a sublimable property. CONSTITUTION:A physiologically active substance (e.g., peonol or caffeine) solid at ordinary temperature and capable of sublimating at 50-220 deg.C is dissolved in an organic solvent, etc., and a solid substrate such as asbestos, incense stick or porous synthetic rubber is impregnated with the prepared solution. The impregnated solid substrate is used as a medicine intactly or preferably after the organic solvent is removed to dry the sublimable substance. The medicine is mixed with an organic solvent, an adhesive substance, etc., to form a coating solution or paste, which is coated on a solid substrate. The peonol and the caffeine have a sedative action and an excitatory action, respectively, and the sublimation-releasable medicine composition is heated to scatter and release the physiologically active substance in air, thereby exhibiting the actions. The medicine composition, for example, prevents sleeping during driving a car and sedates the irritation of nerves due to traffic jams, etc.

Description

Detailed Description of the Invention This invention is a sublimation-release drug composition suitable for absorption through the nasal mucosa, particularly a sublimation-release drug composition obtained by impregnating or coating a solid substrate with a sublimable physiologically active substance. The present invention relates to sex drug compositions. Furthermore, the present invention relates to a delivery system for the above-mentioned sublimation-release drug composition.

Nasal drops are conventionally known as drugs that are administered to the nasal mucosa to treat inflammation, astringency, and sterilization of islet obstruction. This one-drop nasal solution is in liquid form and is used by applying it. Aerosol preparations are a special form of nasal administration, but these preparations are made by suspending herbal medicines, which are normally insoluble in liquefied gas, into a fine powder. Fine herbal medicine particles are obtained as an aerosol. On the other hand, caffeine is a physiologically active substance that is solid at room temperature but has sublimation properties, and has been administered as an oral preparation or an injection.

According to the present invention, there is provided a composition suitable for sublimating a sublimable physiologically active substance, such as paeonol, which has a sedative effect, and caffeine, which has an stimulant effect, and releasing it by scattering it into the air, as well as a system for releasing it. As a result, the present invention relates to formulations and systems that constitute release systems that are a far cry from the known uses of sublimable bioactive substances per se.

The present invention relates to a sublimation-releasing drug composition obtained by impregnating or coating a solid substrate with a sublimable physiologically active substance, and a drug release system in which the composition is heated and released by scattering into the air.

The sublimable physiologically active substance of the present invention is a substance that is solid at room temperature, can be sublimated at about 50°C to 220°C, and has physiological activity. A typical example is peonol (a substance present in peony bark: molecular formula: C0H-o
03. sublimation point 50°C), caffeine (C, H,, N,
02. sublimation point 178℃), menthol (Cl0H200
゜Sublimation point 42℃), Absunsic acid (C+5L.04.Sublimation point 120℃), Camphu 7 (C+otl+eO2
Sublimation point room temperature), borneol (C+oH=aO1 sublimation point 208°C), cinchonine (C1, H22N20. sublimation point 220°C), bergabutene (C, 2H,, O,, sublimation point 188°C), benzoic acid CC? l(,0,.

sublimation point 100°C), salicyl alcohol (C, H80
2° sublimation point 100°C), salicylic acid (C7H1103,
Angelic acid (CsHeO7, sublimation point 45°C), cantharidin (C1oH+zOa, sublimation point 110°C), chrysophane acid (C,,l(,,O,, sublimation point 196°C), aspidos Vermin (C2tHso
Examples include NtOt (sublimation point 180°C).

The solid substrate used in this invention refers to a solid substrate that can be impregnated with a physiologically active substance as a solution or suspension, or that can be coated with a physiologically active substance as a coating solution or paste. Solid substrates that can be impregnated include those that have porosity only on the surface or that penetrate through the interior. Further, the solid base material that can be coated may be any base material that has adhesion to the coating liquid or paste. The material of the base material may be either inorganic or organic, and is selected depending on the place of use. Examples of the base material include porous synthetic rubber, asbestos, shirasu, diatomaceous earth, superficially porous metal, natural or synthetic wood, and natural or synthetic fiber. The solid base material may be in the form of a powder, a rod, or a sheet.

When forming a sublimation-release drug composition into a sheet, it is preferable to use asbestos as the solid base material, and the size of the sublimation-release drug composition mainly depends on the location of use, the content of physiologically active substances, etc. Depending on the relationship:) be selected accordingly. Examples of sizes are 5x 5x O when used inside the house.
, 5cm (vertical x horizontal x thickness).

When the sublimation-releasing drug composition is formed into a rod shape, an incense stick can also be used as the base material.

When impregnating a solid substrate with the drug of this invention, the drug is used after being dissolved in an organic solvent with low pharmaceutical toxicity (eg, water, alcohol, acetone, ethyl acetate, hexane). Although the impregnated substrate may be left as is, it is generally preferable to remove the organic solvent to dry the sublimable substance.

On the other hand, when applying the agent of the present invention to a solid substrate, the agent is prepared by adding an adhesive substance to an organic solvent to form a solution or paste for application. The materials and techniques used to create this solution or paste can be those known in the relevant art.

The amount of the drug impregnated or applied to the base material is not particularly limited. However, the drug is released into the air and absorbed through the nasal mucosa to provide a sufficient amount to be physiologically active. For example, the amount of Paeonol that causes physiological effects on the human body is 200z9 to 1500% for an average body weight of 55.9%.
x9, and caffeine is 30,79-1100z.

The drug release system of the present invention consists of heating the above-mentioned sublimation-releasing drug composition to scatter and release the physiologically active substance into the air, which is usually carried out using heating means. The heating means is a heating medium that can obtain a temperature above the sublimation temperature (but below the decomposition point) of the physiologically active substance, and acts indirectly on the sublimation-releasing drug composition. It is.

Examples of drug release systems in which a heating medium is not directly applied to a sublimation-releasing drug composition include the following.

(1) A system that gradually sublimates physiologically active substances by igniting a sublimation-releasing drug composition formed into an incense stick and subjected to N combustion treatment.

(2) Equipped with a storage section for storing a sublimation-releasing drug composition molded into a temporary shape or sheet shape, and a meter heater whose capacity is set in consideration of the shape, size, etc. of the felled material. A system that sublimates physiologically active substances by filling the composition into a container and heating it with a heater. In addition, in this system, it is preferable that the heater 7) is obtained from an external source, and is preferably provided with a switch for turning on/off the operation of the heater and a temperature adjustment means for adjusting the temperature of the heater.

(3) A sublimation-releasing drug composition is applied to a woven fabric.The second is a system that avoids sublimation of physiological/lingual substances by impregnating the fabric and turning on power to a linear heater embedded in the woven fabric. .

An example of a drug release system in which a heating medium acts indirectly on a sublimation release drug composition is as follows. That is, it is a system in which a physiological substance is sublimated by placing a sublimation-releasing drug composition in an air outlet of a fan heater or the like that blows out heated air.

As described above, the drug release system requires a heating medium, and the heat and soot can be applied to the sublimation-releasing drug composition by a direct method or an indirect method.

Hereinafter, in FIG. 1, a preferred example of the drug release system will be shown and its details will be explained.

Figure 1 shows a drug release system configured so that it can be installed in a car. 1 is a main body made of a heat-resistant thermosetting resin or metal container, and 2 is a removable device on the top of the main body. 3 is a heater provided on the upper part of the main body 1 so as to be in contact with almost the entire bottom surface of the sublimation-releasing drug composition, and 4 is a switch for supplying 7L of electricity to the heater 3. /off switch, 5 is an indicator that lights up when the on/off switch 4 is in the on-state deaf state;
6 is a power supply coat with an L'b connector at the end that can be connected to a car's hemlock light. Reference numeral 7 denotes a suction cup provided on the bottom surface of the main body 1, which is used to removably attach the main body 1 to a vehicle board, console box, or the like. In addition, it is preferable to use a panel type heater as the heater 3 so that it can directly contact the sublimation-releasing drug composition 2.
FIG. 2 is a diagram showing the basic configuration of the electric circuit shown in FIG. 1.

In the figure, when 2V is directly applied from the outside (cigarette lighter) between the A terminal and the B terminal and the switch 4 is turned on, it is applied to the heater 3 via the fuse 10. jlt ZiL
flows and the heater 3 is heated. The heater 3 used has an exothermic temperature at which the sublimation-releasing drug composition 2 can be sublimed. Reference numeral 11 is a bimetal, and by adjusting the gap and setting the upper limit of the heat generation temperature of the heater 3, the heat generation temperature of the heater 3 is controlled to be maintained at a predetermined temperature. In addition, in FIG. 2, the drug j release system can be implemented at home by using an electric circuit having the same configuration as above, with the two external sources applied between terminals A and B being 100 AC.

Next, examples will be shown.

Example 1 Caffeine 29 was dissolved in chloroform 10:1C and D
Cm' is adsorbed onto the asbestos tape, and left to dry at room temperature to create a temporary caffeine-necked asbestos with the solvent completely evaporated. This was heated using an electric heat source controlled at 180°C with a thermostat, and the caffeine was gradually sublimated into the air.The caffeine was then inhaled by a person weighing 55 kg.After 2 minutes, the caffeine was heated in the peritoneal region of the body (left hand). When measuring the temperature distribution on the body surface using thermography, a color change from green to red, indicating a temperature increase of 0.5 to 0.75°C compared to before inhalation, appears on the screen, and it is clear that the obliterated area An increase in body surface temperature was observed. In addition, brain waves before inhalation and 20 minutes after inhalation are observed on an electrode oscillography using potential fluctuations amplified by an electroencephalogram amplifier (electroencephalograph), and are continuously photographed on bromide. The α (alpha) waves of the resting brain waves of 8 to 13 Hz (hertz) decrease after inhalation than on the inhalation side, and the alpha waves of the resting brain waves of 18 to 13 Hz (Hertz), which are observed in excitement, decrease.
Enhancement of β (beta) waves at 30 Hz (hertz) was observed. From this, it is clear that the method of the present invention sublimates caffeine into the air, and when inhaled by humans, its pharmacological effects of promoting blood circulation and causing arousal are also induced.

Example 2 5 g of Paeonol is dissolved in 2011:/, ethanol, adsorbed onto a 10 cm' asbestos board, and left to dry at room temperature to completely scatter the ethanol to create a Paeonol-adsorbed asbestos board. This was placed on an electric heat source controlled at 55℃ using a thermostat, and gradually heated to sublimate the paeonol into the air, resulting in a temperature of 55℃! ? 20 minutes later, when the temperature distribution on the body surface of the peripheral part (left hand) was measured using thermography, a temperature drop of 0.25 to 0.5 degrees Celsius was observed compared to before inhalation, and the brain wave amplifier When electroencephalogram (electroencephalograph) amplitude fluctuations are observed on an electrode oscillography and electroencephalograms are continuously photographed to detect fluctuations in the brain waves, an enhancement of alpha waves is observed, which clearly indicates a sedative effect. It became.

For example, when electrolysis is required, such as when driving a car, caffeine is sublimated and dispersed in the air to prevent sleep, and when you feel nervous due to traffic jams, etc. has a wide range of applications in aromatherapy, which utilizes the sublimation properties of physiologically active substances, such as sublimating and scattering paeonol into the interior of a car to provide sedation. It is thought that this will open up a new field of benefits for aromatherapy that is completely different from the use of aromatic properties.

[Brief explanation of the drawing]

Figure 2 is a perspective view showing an embodiment of the drug J release system of the present invention, and Figure 2 is an electrical circuit diagram of Figure 1. ■...Body, 2...Sublimation-releasing drug composition, 3...Heater, 4...
・On/off switch, 5...indicator,
6...power cord, 7...suction cup

Claims (1)

[Scope of Claims] 1. A sublimation-releasing drug composition obtained by impregnating or coating a solid substrate with a sublimable physiologically active substance. 2. The composition according to claim 1, wherein the physiologically active substance is paeonol or caffeine. 3. A drug release system comprising heating the sublimation-releasing drug composition of claim 1 to scatter and release the physiologically active substance into the air.