Discharge container-packed medical solution

Abstract

To provide a medical solution having excellent flowability capable of spreading over the entire wound surface and retentivity capable of staying in an affected part as medical solution for treating bedsore or damaged skin.SOLUTION: A medical solution for treating bedsore or damaged skin contains medicine for treating bedsore or damaged skin, temperature-responsive polymers which cause gelatinization of the medical solution when the medical solution is exposed to a body temperature of an affected part, and solvent, and is used to be applied to the affected part in a foam state.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to a liquid medicine contained in a dispensing container. [Background technology]

[0002] A pressure ulcer is a condition in which continuous pressure is applied to a certain area of ​​the skin, cutting off blood flow to the skin and causing irreversible ischemic damage, resulting in necrosis of the skin. Pressure ulcers occur when a patient is bedridden, and are also called bed sores. Pharmacological treatments using topical medications are used to control infection and exudate within the pressure ulcer. Such pharmacotherapy plays a central role in the treatment of pressure ulcers. Ointments are mainly used as topical medications for the treatment of pressure ulcers (e.g., Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2004 / 078186 Summary of the Invention [Problem to be solved by the invention]

[0004] The present inventors have noticed that ointments cannot fully exert their therapeutic effect on bedsores due to the following problem: When a bedsore has a wound cavity (pocket) that is larger than the skin defect or when the wound surface has a complex shape, it is difficult to spread the ointment over the entire wound surface. Furthermore, in addition to the complex shape of the wound surface, the affected area of ​​a bedsore can be deformed by the influence of sagging skin in elderly people and external forces on the wound, which can result in the filled ointment not remaining in the wound and leaking onto the skin surrounding the affected area.

[0005] In order to maximize the therapeutic effect of a topical medication for bedsores, it is necessary for the medication to spread over the entire wound surface (fluidity) and remain at the affected area without flowing onto the surrounding skin (retention). Therefore, the object of the present invention is to provide a medicinal solution for treating bedsores or damaged skin that has excellent fluidity to spread over the entire wound surface and retention to remain at the affected area. [Means for solving the problem]

[0006] According to one aspect of the present invention, there is provided a medicinal solution for treating bedsores or damaged skin, comprising: a medicament for treating pressure sores or damaged skin; a temperature-responsive polymer that causes the medicinal solution to gel when exposed to the body temperature of the affected area; Solvent and and a medicinal solution for application to said affected area in the form of a foam, said medicinal solution comprising:

[0007] According to another aspect of the present invention, a medicament for treating pressure sores or damaged skin; a temperature-responsive polymer that causes the medicinal solution to gel when exposed to the body temperature of the affected area; Solvent and a medicinal solution for treating bedsores or damaged skin, comprising: a discharge container that stores the liquid medicine and discharges the liquid medicine in the form of foam; The present invention provides a medicinal liquid in a discharge container, which comprises the above-mentioned components and is used to apply the medicinal liquid to an affected area in the form of foam. [Effects of the Invention]

[0008] According to the present invention, a medicinal liquid for treating bedsores or damaged skin can be provided that has excellent fluidity that allows it to spread over the entire wound surface and excellent retention that allows it to remain in the affected area. [Brief explanation of the drawings]

[0009] [Figure 1]FIG. 10 is a cross-sectional view showing a state in which the medicinal liquid is discharged in the form of foam onto the affected area of ​​a bedsore. [Figure 2] FIG. 10 is a cross-sectional view showing a state in which the medicinal liquid discharged in the form of foam onto the affected area of ​​a bedsore gels at body temperature. [Figure 3] FIG. 2 is a cross-sectional view showing the liquid medicine contained in the dispensing container according to the embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0010] The following describes embodiments of the present invention. The embodiments described below are more specific embodiments of any of the above aspects. The following features can be incorporated into each of the above aspects, either singly or in combination.

[0011] <1> chemical solution The chemical solution is a medicament for treating pressure sores or damaged skin; a temperature-responsive polymer that causes the medicinal solution to gel when exposed to the body temperature of the affected area; Solvent and The medicinal solution for treating bed sores or damaged skin comprises: the medicinal solution being for application to the affected area in the form of a foam.

[0012] The medicinal solution can be contained in a discharge container that discharges foam, and can be used by discharging the foam from the discharge container onto the affected area. In this specification, a product in which a medicinal solution is contained in a discharge container is referred to as a "medicinal solution contained in a discharge container." In the technical field, a product in which a medicinal solution is contained in a discharge container is also referred to as a "foam preparation" or a "foam spray."

[0013] <1.1> When the medicinal solution is applied to the affected area of ​​a bedsore The medicinal liquid is preferably a medicinal liquid for treating bedsores. The case where the medicinal liquid is applied to an affected area of ​​a bedsore will be described with reference to Figs.

[0014] Figure 1 shows a schematic diagram of a medicinal solution being dispensed in the form of foam onto a bedsore. In Figure 1, a wound cavity, i.e., a pocket 400, which is wider than the defect in the epidermis 300a, has been formed in the bedsore. The pocket 400 is formed in the area where the bone 300e protrudes. In terms of depth, the pocket 400 extends beyond the skin (composed of the epidermis 300a, dermis 300b, and subcutaneous tissue 300c) to the muscle 300d. The pocket 400 is formed when necrotic tissue dissolves and is expelled.

[0015] FIG. 1 shows a state in which a liquid medicinal solution 200a is discharged in the form of foam from a dispensing container 100 onto an affected area accompanied by such skin damage. In FIG. 1, the medicinal solution in the form of foam is indicated by the symbol 200b. The medicinal solution 200b in the form of foam can be filled into the wound so as to reach the entire wound surface of the pocket 400. The pocket 400 has a deep recess 400a, and the medicinal solution 200b in the form of foam can also be filled into this recess 400a. Even if the wound surface of the pocket 400 has a complex shape in this way, because the medicinal solution is in the form of foam, it can be filled into the wound so as to reach the entire wound surface (i.e., every corner of the wound surface). Here, for example, a pump former or an aerosol can can be used as the dispensing container 100.

[0016] Thereafter, the medicinal solution 200b in foam form gels when exposed to the body temperature of the affected area because it contains a temperature-responsive polymer. The body temperature of the affected area is usually within the range of 35 to 37°C. Figure 2 shows the medicinal solution dispensed in foam form onto the affected area of ​​a bedsore and gelling at body temperature. In Figure 2, the gelled medicinal solution is indicated by the symbol 200c. The medicinal solution 200b in foam form mixes with the exudate seeping out of the bedsore, defoams, and gels in a shape that conforms to the wound surface. As a result, the gelled medicinal solution 200c can remain at the affected area without flowing out onto the skin surrounding the affected area.

[0017] <1.2> Composition of the chemical solution Next, the composition of the chemical solution will be described.

[0018] (drug) The drug contained in the medicinal solution can be an active ingredient of a drug currently on the market for treating wounds, including bedsores and skin ulcers. Preferably, the drug contained in the medicinal solution can be an active ingredient of a drug currently on the market for treating bedsores. That is, the drug is preferably a drug for treating bedsores.

[0019] Preferably, the drug may be at least one selected from the group consisting of an antibacterial agent, a cell growth promoter, and a tissue removing agent. More preferably, the drug may be at least one selected from the group consisting of an antibacterial agent and a cell growth promoter. The drug may be one type or two or more types.

[0020] For example, the following drugs can be used as drugs. The main effects of the drugs exemplified below are described in parentheses.

[0021] (A) Antibacterial agent A combination of refined white sugar and povidone-iodine (wound healing and antiseptic properties) A combination of carmellose sodium and iodine (antibacterial and exudate absorbing properties) Cadexomer iodine (antibacterial and exudate absorbing properties) Silver sulfadiazine (antibacterial effect)

[0022] (B) Cell proliferation promoter Tretinoin, tretinoin tocopheryl (promotes granulation and skin damage healing) Trafermin (promotes wound healing and granulation) Alprostadil alfadex (promotes epidermal formation and wound healing) Bucladesine sodium (promotes granulation and epidermal formation)

[0023] (C) Debriding agent Bromelain (decomposes, removes, and cleanses necrotic tissue on the wound surface, and promotes wound healing)

[0024] The above-mentioned drugs are currently used in dosage forms other than foam formulations (e.g., ointments or atomized sprays) as active ingredients in drugs for treating wounds, including bedsores and skin ulcers. Therefore, the content of the drug in the drug solution can be the same concentration as the concentration of the drug in the currently used drug (drug in a dosage form other than foam formulations).

[0025] For example, when the drug is povidone-iodine, the content of povidone-iodine in the drug solution can be, for example, within the range of 0.1 to 10% by mass. When the drug is tretinoin, the content of tretinoin in the drug solution can be, for example, within the range of 0.1 to 10% by mass. When the drug is trafermin, the content of trafermin in the drug solution can be, for example, within the range of 0.1 to 10% by mass. The drug concentration is not limited to the above ranges and can be appropriately set based on pharmacological efficacy tests.

[0026] (Temperature-responsive polymer) The temperature-responsive polymer induces gelation (i.e., sol-gel transition) of the drug solution when the drug solution is exposed to the body temperature of the affected area. Preferably, the temperature-responsive polymer induces thermoreversible gelation of the drug solution when the drug solution is exposed to the body temperature of the affected area. The temperature-responsive polymer may also be referred to as a temperature-responsive gelling agent.

[0027] The temperature-responsive polymer can also function as a foaming agent. The temperature-responsive polymer preferably has low foaming properties. A low-foaming temperature-responsive polymer is preferred because the drug solution easily defoams between the time the drug solution is discharged in the form of foam and the time the drug solution gels.

[0028] As the temperature-responsive polymer, for example, a Pluronic surfactant can be used. The Pluronic surfactant has the following formula: HO-(EO)m-(PO)n-(EO)mH In this general formula, EO represents ethylene oxide, PO represents propylene oxide, m represents the degree of polymerization of ethylene oxide, and n represents the degree of polymerization of propylene oxide. m represents an integer of, for example, 95 to 105, and n represents an integer of, for example, 54 to 60. In other words, Pluronic surfactants are polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymers.

[0029] Various Pluronic surfactants are commercially available, differing in the degree of polymerization of ethylene oxide and propylene oxide. The number-average molecular weight of Pluronic surfactants is preferably in the range of about 5,000 to about 15,000, more preferably about 10,000 to about 15,000. The ethylene oxide content of Pluronic surfactants is preferably in the range of about 50 to about 90% by weight, more preferably about 60 to about 80% by weight. The number-average molecular weight of polypropylene oxide in Pluronic surfactant molecules is preferably in the range of about 2,000 to about 5,000, more preferably about 3,000 to about 5,000.

[0030] For example, poloxamer 407 can be used as a temperature-responsive polymer. Poloxamer 407 is included in the Pluronic surfactants. In the case of poloxamer 407, m is 101 and n is 56 in the above formula. Poloxamer 407 has a chemical structure similar to Pluronic (registered trademark) F-127. Poloxamer 407 has a number-average molecular weight of approximately 12,600, an ethylene oxide content in the molecule of approximately 70% by mass, and a number-average molecular weight of polypropylene oxide in the molecule of approximately 4,000. Poloxamer 407 is known to have low foaming properties. Poloxamer 407 is available, for example, from BASF Japan Ltd. under the trade name Corifol (registered trademark) P407.

[0031] From the above, it is possible to use polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymers as temperature-responsive polymers.

[0032] Temperature-responsive polymers are not limited to Pluronic surfactants or polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymers. In other words, other materials that have been reported to undergo sol-gel transitions in response to temperature changes, similar to Pluronic surfactants, can also be used as temperature-responsive polymers. For example, poly(N-alkylacrylamide), polyethylene glycol block copolymers, hydroxypropylmethylcellulose, methylcellulose, and mixtures of poly(ethylene glycol) and chitosan can also be used as temperature-responsive polymers.

[0033] The temperature-responsive polymer can be contained in the drug solution at a concentration of, for example, 12.5 to 31.0 mass %, preferably 15.0 to 30.0 mass %, more preferably 17.5 to 27.0 mass %, and even more preferably 20.0 to 26.0 mass %. The above concentration range of the temperature-responsive polymer is suitable for inducing a sol-gel transition of the drug solution. In addition, the above concentration range of the temperature-responsive polymer is suitable for inducing a sol-gel transition of the drug solution at a concentration of 0.5 g / cm. 3 It is suitable for discharging foam having the following foam density from the dispensing container: When the concentration of the temperature-responsive polymer in the chemical solution increases, the viscosity of the chemical solution increases, and the foam density tends to increase.

[0034] When the drug is povidone-iodine, the content of the temperature-responsive polymer in the drug solution can be preferably within the range of 20.0 to 26.0% by mass. When the drug is tretinoin, the content of the temperature-responsive polymer in the drug solution can be preferably within the range of 15.0 to 27.0% by mass. When the drug is trafermin, the content of the temperature-responsive polymer in the drug solution can be preferably within the range of 17.5 to 30.0% by mass.

[0035] Because the medicinal solution contains a temperature-responsive polymer, it may gel if placed at temperatures above body temperature. Since the medicinal solution is applied to the affected area in the form of a foam, it must be in liquid (sol) form at the time of application. Therefore, it is desirable to maintain the medicinal solution in its liquid (sol) form by placing it at a temperature that will prevent the medicinal solution from gelling, at least immediately before use. For example, it is desirable to store the medicinal solution at a temperature of 2 to 20°C until use. Furthermore, it is desirable to store the medicinal solution at a temperature of 2 to 8°C until use.

[0036] (solvent) The solvent may be any solvent commonly used in foam formulations for topical skin applications, and is preferably purified water.

[0037] The drug solution may further contain additives for liquid formulations, as needed, such as antioxidants, preservatives, pH adjusters, stabilizers, solubilizers, foaming agents, antifoaming agents, and gelling agents.

[0038] The medicinal solution can be applied to the affected area in the form of foam so that it can be distributed over the entire affected area. When the medicinal solution is contained in a foam-discharging container, the medicinal solution can be applied to the affected area by a single discharge, or by multiple discharges (e.g., 2 to 5 times). The amount of foam discharged from the foam-discharging container can be, for example, within the range of 0.5 to 1.0 g. The number of discharges can be determined appropriately depending on the size and severity of the affected area.

[0039] <1.3> Physical properties of chemical solutions The physical properties of the drug solution are described below. The following physical property values ​​refer to values ​​measured according to the procedures described in the Examples.

[0040] (Viscosity of the drug in liquid form) The liquid medicine can have any viscosity as long as it can be discharged in the form of foam from a discharge container that discharges the medicine in the form of foam. The liquid medicine has a viscosity, for example, in the range of 20 to 160 mPa·s (see Tables 2, 8, and 14 described below). If the viscosity of the medicine is within the above range, fine bubbles can be discharged when the medicine is discharged from the discharge container. As the viscosity of the medicine increases, the bubble density tends to increase.

[0041] In this specification, the viscosity of a chemical solution refers to a value measured using a Brookfield viscometer. In this specification, unless a temperature is specified for the viscosity of a chemical solution, the viscosity refers to the viscosity of the chemical solution at 5°C.

[0042] (Foam density of the drug solution in foam form) The foam density of the liquid medicine varies slightly depending on the type of discharge container, but is, for example, 0.1 to 0.5 g / cm 3 , preferably 0.1 to 0.4 g / cm 3 (See Tables 3, 9, and 15 below.) Thus, when the drug solution is discharged in the form of foam from the discharge container, the foam density (0.1 to 0.5 g / cm) is generally defined as the foam density. 3 ) can be shown.

[0043] (Physical properties of gelled drug solution) When a medicinal solution in the form of a foam and Ringer's solution (a substitute for exudate) are mixed in a mass ratio of 10:3 and the mixture is allowed to gel at 37°C, the resulting gel can exhibit the following physical properties:

[0044] The loss factor (tan δ) at a strain of 0.1% is, for example, in the range of 0.01 to 0.3, preferably 0.01 to 0.2 (see Tables 4, 10, and 16 below). The loss factor (tan δ) is a value calculated by the formula: loss modulus (G") / storage modulus (G'), and therefore a loss factor (tan δ) value of less than 1 indicates that the properties of a solid are dominant. Therefore, when a medicinal solution is discharged in the form of foam from a discharge container and then gels at a temperature around body temperature, it can form a gel in which the properties of a solid are dominant.

[0045] The yield value measured by a parallel plate viscometer is, for example, 7000 dyn / cm 2 Less than 5000 dyn / cm 2 Less than or equal to 3000 dyn / cm 2 The yield value is as follows (see Tables 5, 11, and 17 below). The smaller the yield value, the softer and more easily spreadable the gel is. Therefore, when the medicinal liquid is discharged in the form of foam from the discharge container and then gelled at a temperature close to body temperature, it can form a soft and easily spreadable gel.

[0046] The adhesiveness value measured by a texture analyzer is, for example, 40 J / m 2 Less than or equal to 30 J / m 2 Less than or equal to 20 J / m 2 The adhesiveness values ​​are as follows (see Tables 6, 12, and 18 below). The smaller the adhesiveness value, the less likely the medicinal liquid is to adhere to the affected area to which it is applied. Therefore, when the medicinal liquid is discharged in the form of foam from the discharge container and then gels at a temperature close to body temperature, it can form a gel that has low adhesiveness to the affected area.

[0047] <1.4> Effects The medicinal solution described above is applied to the affected area in the form of a foam, and therefore has excellent fluidity, can be easily spread over the entire affected area, and can be easily applied over a wide area. Therefore, the medicinal solution described above can be applied so that it reaches the entire wound surface (i.e., every corner of the wound surface) even if the wound surface has a complex shape. Furthermore, when the medicinal solution described above is applied to the affected area, it is exposed to the body temperature of the affected area and converted into a gel. Therefore, the medicinal solution remains at the affected area without flowing out onto the skin surrounding the affected area, and the medicinal effect of the medicinal solution can be exerted for a long period of time. Therefore, according to the present invention, a medicinal solution for treating bedsores or damaged skin can be provided that has excellent fluidity that allows it to reach the entire wound surface and excellent retention that allows it to remain at the affected area.

[0048] <2> Chemical solution in a discharge container As described above, the medicinal liquid can be stored in a discharge container that discharges foam, and can be used by discharging the foam from the discharge container to the affected area. Therefore, according to another aspect, there is provided a product in which the medicinal liquid is stored in a discharge container, i.e., a medicinal liquid contained in a discharge container.

[0049] The chemical solution in the discharge container is a medicament for treating pressure sores or damaged skin; a temperature-responsive polymer that causes the medicinal solution to gel when exposed to the body temperature of the affected area; Solvent and a medicinal solution for treating bedsores or damaged skin, comprising: a discharge container that stores the liquid medicine and discharges the liquid medicine in the form of foam; and is used to apply the medicinal liquid in the form of foam to the affected area.

[0050] The liquid medicine in the discharge container is, for example, 0.1 to 0.5 g / cm 3 , preferably 0.1 to 0.4 g / cm 3 It is possible to discharge foam at a foam density within the range of

[0051] The medicinal liquid in the discharge container is discharged in the form of foam onto the affected area of ​​a bedsore or damaged skin, and therefore can achieve the same effects as those of the medicinal liquid described above in the section "<1.4> Effects." That is, when the medicinal liquid in the discharge container is discharged in the form of foam onto the affected area of ​​a bedsore or damaged skin, the medicinal liquid can be applied so that it reaches the entire wound surface (i.e., every corner of the wound surface), and the medicinal liquid can be retained at the affected area without flowing out onto the skin around the affected area.

[0052] The discharge container can be of any shape as long as it can discharge the liquid medicine in the form of foam. Examples of discharge containers that can be used include pump formers and aerosol cans. When the nozzle of a pump former is pressed, the liquid contents are mixed with air, and the mixture passes through a porous body, thereby discharging the contents in the form of foam. In an aerosol can, the liquid contents and liquefied gas or compressed gas are filled in a pressure-resistant container, and when the spray button is pressed, the contents are sprayed out in foam due to the pressure of the gas.

[0053] The discharge container (pump former) according to one embodiment is: a container body containing a drug solution; a discharge device attached to the container body; Equipped with The discharge device is a pump unit having an air chamber, a liquid chamber, and a mixing chamber therein, and performing a foam generating operation in which the chemical liquid obtained from the container body into the liquid chamber and the air in the air chamber are supplied to the mixing chamber during a pumping operation to generate foam consisting of the chemical liquid and the air, and a preparatory operation in which the chemical liquid is obtained from the container body into the liquid chamber and air in an external space is introduced into the air chamber; a nozzle unit having an internal discharge flow path through which the foam passes and discharging the foam; a porous body including one or more meshes that is placed in the discharge flow path and through which the bubbles pass; It is equipped with:

[0054] The liquid medicine contained in the discharge container having the discharge container according to the embodiment is shown in Fig. 3. Fig. 3 is a cross-sectional view showing the liquid medicine contained in the discharge container.

[0055] The medicinal solution in a discharge container 10A shown in Fig. 3 includes a discharge container 1 and a medicinal solution 200. As described above, the medicinal solution 200 includes a drug, a temperature-responsive polymer, and a solvent. The medicinal solution in a discharge container 10A is used to apply the medicinal solution 200 in the form of a foam to an affected area of ​​a bedsore or damaged skin.

[0056] The configuration and operation of the discharge container 1 will be described below.

[0057] <2.1> Configuration of the discharge container The dispensing container 1 includes a container body 2, a dispensing device 3, and a tube 4. The dispensing container 1 is a so-called hand pump that dispenses the medicinal liquid 200 contained in the container body 2 in the form of foam by the dispensing device 3. In the following description, the container body 2 side of the dispensing container 1 is referred to as the bottom, and the nozzle unit 16 side of the dispensing device 3 is referred to as the top.

[0058] The container body 2 is cylindrical and has a bottom. The container body 2 is open at its upper end. The upper end of the container body 2, including this opening, includes a cylindrical first fixing portion 11. The first fixing portion 11 has a male screw portion 12 on its outer circumferential surface.

[0059] The discharge device 3 includes a support member 15, a nozzle unit 16, a pump unit 17, and a porous body 18. The discharge device 3 is fixed to the container body 2 by the support member 15.

[0060] The support member 15 includes a first fixed portion 21 and a second fixing portion 23. The support member 15 is, for example, an integrally molded product made of resin.

[0061] The first fixed part 21 has a cylindrical shape with a constant diameter at one opening side and a diameter decreasing toward the other opening side. The part of the first fixed part 21 at one opening side is located below the part at the other opening side. The inner peripheral surface of the part of the first fixed part 21 at one opening side faces the outer peripheral surface of the first fixed part 11. This inner peripheral surface has a female screw part 25 that screws into the male screw part 12 of the first fixed part 11. In this way, the first fixed part 21 is fixed to the first fixed part 11 of the container body 2.

[0062] The second fixing portion 23 has a cylindrical shape. The second fixing portion 23 is located inside the first fixing portion 21. The upper end of the second fixing portion 23 is continuous with the upper end of the first fixing portion 21.

[0063] The outer cylinder portion 31 of the nozzle unit 16 is inserted into the second fixed portion 23. The inner peripheral surface of the second fixed portion 23 protrudes inward along its entire circumference at its upper end. This protrusion constitutes the first guide portion 22 that guides the nozzle unit 16 when it moves up and down.

[0064] The nozzle unit 16 includes an outer cylinder 31, an inner cylinder 32, a top plate 33, and a nozzle 36. The nozzle unit 16 is an integrally molded product made of, for example, resin. The nozzle unit 16 has a discharge flow path 34 within the inner cylinder 32 and the nozzle 36, through which the chemical solution 200 passes.

[0065] The outer cylinder 31 is inserted into a ring formed by the first guide part 22. The inner cylinder 32 is installed inside the outer cylinder 31 so that its outer peripheral surface faces the inner peripheral surface of the outer cylinder 31. The inner cylinder 32 has therein a cylindrical first flow path part 35 that forms part of the discharge flow path 34.

[0066] The top plate portion 33 closes the upper openings of the outer cylinder portion 31 and the inner cylinder portion 32. The top plate portion 33 forms a part of the nozzle portion .

[0067] The nozzle portion 36 has a tubular shape, for example, a cylindrical shape, protruding obliquely upward from the upper end of the outer tubular portion 31. The nozzle portion 36 has a second flow path portion 39 therein that communicates with the first flow path portion 35 of the inner tubular portion 32.

[0068] The pump unit 17 includes a cylinder unit 41, a piston 42, a valve portion 43, and a biasing member 44. The pump unit 17 has a first air chamber 45, a second air chamber 46, a liquid chamber 47, and a mixing chamber 48 inside.

[0069] The cylinder unit 41 includes a first cylinder portion 51, a second cylinder portion 52, a second fixed portion 53, and an attachment portion 54. The cylinder unit 41 is, for example, an integrally molded product made of resin.

[0070] Each of the first cylinder portion 51, the second cylinder portion 52, the second fixed portion 53, and the mounting portion 54 has a cylindrical shape and is installed so that one opening faces upward and the other opening faces downward. The first cylinder portion 51, the second cylinder portion 52, the second fixed portion 53, and the mounting portion 54 are arranged coaxially.

[0071] A through-hole 51a is provided in the wall of the first cylinder portion 51, which connects the internal space of the first cylinder portion 51 with the internal space of the container body 2. The through-hole 51a is located below the opening of the container body 2 and above the liquid level of the medicinal solution 200.

[0072] The upper end of the first cylinder portion 51 is continuous with the lower end of the second fixed portion 53 .

[0073] The second fixed part 53 is fitted with the second fixed part 23 so that the second fixed part 53 is positioned outside the second fixed part 23. The second fixed part 53 has a flange part 53b on its outer circumferential surface. The flange part 53b is pressed upward by the first fixed part 11 via the seal member 53a. In this way, the cylinder unit 41 is fixed to the container body 2 and the support member 15.

[0074] The second cylinder portion 52 has a smaller diameter than the first cylinder portion 51. The upper end of the second cylinder portion 52 is continuous with the lower end of the first cylinder portion 51.

[0075] The upper end of the mounting portion 54 is continuous with the lower end of the second cylinder portion 52. The upper end of the mounting portion 54 has a constant diameter that is smaller than the diameter of the lower end of the second cylinder portion 52. As a result, a step including an annular seat surface 52a is formed on the inner surface of the cylinder unit 41 at the connection between the mounting portion 54 and the second cylinder portion 52.

[0076] The lower end of the mounting portion 54 has a constant diameter, which is smaller than the diameter of the upper end of the mounting portion 54.

[0077] The diameter of the middle part of the attachment part 54 decreases from top to bottom, and the inner surface of this middle part forms a first valve seat 55 that tapers from top to bottom.

[0078] The piston 42 includes a rod portion 61, a first piston portion 62, and a second piston portion 63. The combination of the rod portion 61 and the first piston portion 62 is, for example, an integrally molded product made of resin.

[0079] The rod portion 61 includes a first fitting portion 65 , a second fitting portion 67 , and a mixing portion 66 .

[0080] The first fitting portion 65 is one end of the rod portion 61. The first fitting portion 65 has a cylindrical shape. The first fitting portion 65 fits into the lower end of the inner cylindrical portion 32 so that one end of the first fitting portion 65 is located inside the inner cylindrical portion 32. The first fitting portion 65 has a protrusion 65a on its outer surface spaced a predetermined distance from the upper end. The protrusion 65a abuts against the lower end face of the inner cylindrical portion 32.

[0081] The second fitting portion 67 is the other end of the rod portion 61. The second fitting portion 67 has a cylindrical shape. The diameter of the second fitting portion 67 is larger than that of the first fitting portion 65. One bottom surface of the second fitting portion 67 is continuous with the lower end of the first fitting portion 65. The second fitting portion 67 has a through hole extending from one bottom surface to the other bottom surface. A groove is provided in the side wall of this through hole between a second fitted portion 81 (described later) and the second fitting portion 67, forming a flow path that connects the first air chamber 45 and the mixing chamber 48.

[0082] The mixing portion 66 is a protrusion that protrudes upward from the upper surface of the second fitting portion 67 within the first fitting portion 65. Specifically, the mixing portion 66 has a cylindrical shape with a bottom. The bottom of the mixing portion 66 is located above the opening. The mixing portion 66 has an internal space as the mixing chamber 48. A through hole 66a is provided in the bottom of the mixing portion 66, connecting the external space with the mixing chamber 48. The mixing portion 66 has a plurality of protrusions 66b on its inner surface.

[0083] The first piston portion 62 includes a first sliding portion 71 and a connecting portion 72 .

[0084] The first sliding portion 71 has a cylindrical shape that is narrowed at the middle position in the height direction. The narrowed portion of the first sliding portion 71 is a body portion 71a, and the portions positioned above and below the body portion 71a are end portions 71b.

[0085] The first sliding portion 71 is installed inside the first cylinder portion 51. Each end portion 71b of the first sliding portion 71 is in contact with the inner circumferential surface of the first cylinder portion 51 over its entire circumference. The body portion 71a is spaced apart from the inner circumferential surface of the first cylinder portion 51. The first sliding portion 71 is slidable in the up and down direction relative to the first cylinder portion 51.

[0086] The connecting portion 72 connects the first sliding portion 71 to the second fitting portion 67. The connecting portion 72 has a cylindrical shape. The connecting portion 72 surrounds the second fitting portion 67. The connecting portion 72 and the second fitting portion 67 are continuous at their upper ends, and a cylindrical groove 74 is formed between them. The connecting portion 72 has a flange portion at its lower end. The outer periphery of the flange portion is continuous with the inner periphery of the first sliding portion 71. A through hole 73 is provided in this flange portion near the groove 74.

[0087] The second piston portion 63 includes a second fitted portion 81, a second sliding portion 82, and a flange portion.

[0088] The second piston portion 63 has a cylindrical shape. The second piston portion 63 includes a second fitted portion 81 at one end and a second sliding portion 82 at the other end.

[0089] The second fitted portion 81 is fitted into the second fitting portion 67. The upper portion of the inner circumferential surface of the second fitted portion 81 has a diameter that decreases from top to bottom, and forms the second valve seat 83. As described above, the groove provided in the side wall of the through hole of the second fitting portion 67 forms a flow path between the second fitted portion 81 and the second fitting portion 67 that connects the first air chamber 45 and the mixing chamber 48.

[0090] The second sliding portion 82 has an outer peripheral surface at least at its lower end portion that contacts the inner peripheral surface of the second cylinder portion 52 over the entire circumference. The second sliding portion 82 is slidable relative to the second cylinder portion 52 in the up and down direction.

[0091] The inner diameter of the upper end of the second sliding portion 82 is smaller than the inner diameter of the lower end of the second fitted portion 81. As a result, a step including the annular first seating surface portion 84 is formed on the inner surface of the second piston portion 63 at the connection portion between the second fitted portion 81 and the second sliding portion 82.

[0092] The flange portion of the second piston portion 63 is provided at the upper end of the second sliding portion 82. The upper surface of this flange portion is a third valve seat 85.

[0093] The valve portion 43 includes a first valve body 91 , a second valve body 92 , a third valve body 93 , and a second guide portion 94 .

[0094] The first valve body 91 is a sphere made of, for example, metal or resin. The first valve body 91 is installed in a recess formed by the first valve seat 55. The first valve body 91 is in annular contact with the first valve seat 55 due to its own weight or the like. When a flow of the chemical solution 200 occurs from the attachment part 54, the first valve body 91 moves away from the first valve seat 55.

[0095] The second valve body 92 is a poppet valve made of resin. The second valve body 92, together with the second valve seat 83, forms a discharge portion that discharges the chemical liquid 200 from the liquid chamber 47.

[0096] The second valve body 92 includes a valve body portion 92a and a shaft body 92b.

[0097] The valve body portion 92a has a shape that conforms to the second valve seat 83. The valve body portion 92a is recessed at the top, forming an internal space that tapers downward. The outer circumferential surface of the valve body portion 92a abuts against the second valve seat 83. When the nozzle unit 16 is operated, the second piston portion 63 moves following the nozzle unit 16, and the second valve seat 83 moves away from the valve body portion 92a.

[0098] The upper end of the shaft body 92b is continuous with the lower end of the valve body portion 92a. A protrusion 92c having a diameter larger than that of the shaft body 92b is provided at the lower end of the shaft body 92b.

[0099] The third valve body 93 includes a fixed body 93a, a first on-off valve 93b, and a second on-off valve 93c. The third valve body 93 is an integrally molded product made of an elastically deformable material such as rubber.

[0100] The fixed body 93a has a cylindrical shape. The fixed body 93a is fitted into a groove 74 provided in the connecting portion 72. In this way, the third valve body 93 is fixed to the first piston portion 62.

[0101] The first on-off valve 93b is provided on the outer periphery of the lower end of the fixed body 93a. The first on-off valve 93b abuts against the lower surface of the connecting portion 72, thereby closing the through-hole 73.

[0102] The second on-off valve 93c is provided on the inner periphery of the lower end of the fixed body 93a. The second on-off valve 93c abuts against the third valve seat 85 of the second piston portion 63, thereby closing the flow path connecting the first air chamber 45 and the mixing chamber 48.

[0103] The second guide portion 94 is made of, for example, resin, and includes a cylindrical portion, a second seating surface portion 94a, and a protrusion portion 94c.

[0104] The cylindrical portion of the second guide portion 94 extends in the length direction within the second cylinder portion 52. A plurality of slits 94b are provided in the wall of the cylindrical portion, each extending in the length direction of the cylindrical portion. The second seating surface portion 94a protrudes in an annular shape from the outer periphery of the lower end of the cylindrical portion. The protrusion 94c protrudes in an annular shape from the inner periphery of the upper end of the cylindrical portion. The protrusion 94c abuts against the protrusion 92c of the second valve body 92, thereby restricting the movement of the second valve body 92.

[0105] The biasing member 44 is a coil spring made of metal. The biasing member 44 is installed between the first seating surface portion 84 and the second seating surface portion 94a. The biasing member 44 biases the second piston portion 63 and the second guide portion 94 in directions separating them from each other via the first seating surface portion 84 and the second seating surface portion 94a.

[0106] The first air chamber 45 is a space surrounded by the first cylinder portion 51, the first piston portion 62, and the second piston portion 63. The volume of the first air chamber 45 changes with the reciprocating motion of the first piston portion 62. The first air chamber 45 communicates with the second air chamber 46 via the through hole 73, and also communicates with the mixing chamber 48 via a flow path formed by the groove of the second fitting portion 67.

[0107] The second air chamber 46 is made up of a space sandwiched between the outer cylinder portion 31 and the inner cylinder portion 32, and a space surrounded by the second fixed portion 23, the first cylinder portion 51, the rod portion 61, and the first piston portion 62. The second air chamber 46 communicates with the outside space via the gap between the first guide portion 22 and the outer cylinder portion 31. Furthermore, when the end portion 71b of the first piston portion 62 is positioned below the through-hole 51a of the first cylinder portion 51, the second air chamber 46 communicates with the space inside the container body 2 via this through-hole 51a.

[0108] The liquid chamber 47 is a space surrounded by the second cylinder portion 52, the second piston portion 63, the first valve body 91, and the second valve body 92. The volume of the liquid chamber 47 changes with the reciprocating motion of the second piston portion 63. When the first valve body 91 moves away from the first valve seat 55, the liquid chamber 47 communicates with the interior of the container body 2 via the attachment portion 54 and the tube 4. When the valve body portion 92a of the second valve body 92 moves away from the second valve seat 83 of the second piston portion 63, the liquid chamber 47 communicates with the mixing chamber 48.

[0109] The mixing chamber 48 is a space within the mixing section 66. The mixing chamber 48 is in communication with the secondary-side discharge flow path 34 via the through-hole 66a. The mixing chamber 48 mixes the air and the chemical solution 200, and supplies the chemical solution 200 mixed with air to the secondary side via the through-hole 66a.

[0110] The porous body 18 includes a holder 18a, a first mesh 18b, and a second mesh 18c. The chemical solution 200 is mixed with air in the mixing chamber 48 to form bubbles, and the size of each bubble decreases as the chemical solution passes through the porous body 18.

[0111] The holder 18a has a cylindrical shape and is fitted into the first fitting portion 65.

[0112] The upper and lower openings of the holder 18a each have an opening area of ​​0.2 to 0.7 cm 2 Preferably, the thickness is in the range of 0.3 to 0.4 cm 2 It is more preferable that the opening area of ​​the upper opening of the holder 18a and the opening area of ​​the lower opening of the holder 18a are in the range of 1 / 2.0 mm to 1 / 4.0 mm. Although the opening areas of the upper opening and the lower opening of the holder 18a may be different, it is preferable that they have the same opening area.

[0113] The first mesh 18b is a porous sheet and is placed in the opening below the holder 18a.

[0114] The mesh number M1 of the first mesh 18b is preferably in the range of 60 to 330, and more preferably in the range of 90 to 260. The mesh number is the number of meshes per inch. For example, the mesh number M2 of the second mesh 18c is in the same range as the mesh number M1 of the first mesh 18b. The mesh number M2 of the second mesh 18c is preferably equal to or greater than the mesh number M1 of the first mesh 18b.

[0115] The wire diameter R1 of the first mesh 18b is preferably in the range of 30 to 80 μm, and more preferably in the range of 40 to 70 μm. The wire diameter R2 of the second mesh 18c is equal to the wire diameter R1 of the first mesh 18b.

[0116] The second mesh 18c is a porous sheet and is placed in the opening above the holder 18a.

[0117] The distance from the first mesh 18b to the second mesh 18c is preferably in the range of 10 to 20 mm, and more preferably in the range of 12 to 16 mm.

[0118] The discharge flow path 34 is made up of the through-hole 66a, the internal space of the holder 18a, the first flow path portion 35, and the second flow path portion 39. The discharge flow path 34 forms a flow path that leads from the mixing chamber 48 to the opening at the tip of the nozzle portion 36.

[0119] The tube 4 is flexible. One end of the tube 4 is fitted into the attachment portion 54, and the other end is located near the bottom of the container body 2.

[0120] The discharge container 1 has a volume V1 (cm ) of air discharged under atmospheric pressure in a foam generating operation described later. 3 ) but 4 to 30 cm 3 It is preferable that the mass V2 (g) of the medicinal liquid 200 discharged in this foam generating operation is in the range of 0.3 to 15 g.

[0121] <2.2> Operation of the discharge container Next, the discharge of the chemical solution 200 using the discharge container 1 will be described. In the discharge container 1 before the start of the foam generating operation, the biasing member 44 biases the second piston portion 63 in a direction away from the second guide portion 94. Therefore, the nozzle unit 16 and the piston 42 are maintained at the top dead center.

[0122] When the nozzle unit 16 and the piston 42 are positioned at top dead center, the first air chamber 45 and the liquid chamber 47 each have a maximum volume. Furthermore, when the nozzle unit 16 and the piston 42 are positioned at top dead center, the first valve body 91, the second valve body 92, and the third valve body 93 are in a closed state. That is, the first air chamber 45 and the second air chamber 46 are isolated from each other, the first air chamber 45 and the mixing chamber 48 are isolated from each other, and the liquid chamber 47 and the mixing chamber 48 are isolated from each other.

[0123] The foam generating operation is initiated by pressing the nozzle unit 16 in a direction that brings the nozzle unit 16 closer to the container body 2. When the nozzle unit 16 is pressed, the piston 42 moves from the top dead center toward the bottom dead center. Specifically, the first piston portion 62 and the second piston portion 63 move toward the bottom dead center, and the volumes of the first air chamber 45 and the liquid chamber 47 gradually decrease.

[0124] At this time, the air in the first air chamber 45 is compressed by the first piston portion 62 and becomes higher in pressure than atmospheric pressure. As a result, the second on-off valve 93c is pressed by the air in the first air chamber 45 and moves in a direction away from the third valve seat 85, becoming open. At the same time, the first on-off valve 93b becomes closed. As a result, the first air chamber 45 communicates with the mixing chamber 48 via the groove of the second fitting portion 67, and the air in the first air chamber 45 flows into the mixing chamber 48.

[0125] At this time, as the volume of the liquid chamber 47 decreases, the pressure of the liquid chemical 200 and air in the liquid chamber 47 also becomes higher than atmospheric pressure. As a result, the first valve body 91 is pressed toward the first valve seat 55 by the liquid chemical 200 in the liquid chamber 47. The valve body portion 92a is also pressed in a direction away from the second valve seat 83, and the second valve body 92 is set to an open state. As a result, the liquid chamber 47 communicates with the mixing chamber 48, and the liquid chemical 200 in the liquid chamber 47 flows into the mixing chamber 48.

[0126] In this way, the air in the first air chamber 45 and the chemical solution 200 in the liquid chamber 47 flow into the mixing chamber 48, whereby the chemical solution 200 is mixed with the air. The chemical solution 200 mixed with the air in the mixing chamber 48 passes through the porous body 18, whereby each of the bubbles made of the chemical solution 200 and the air is broken down into fine particles and the bubbles are homogenized. The chemical solution 200 in the form of bubbles thus generated is discharged from the opening of the nozzle portion 36.

[0127] The foam generating operation ends when the first piston portion 62 and the second piston portion 63 reach bottom dead center. When the first piston portion 62 and the second piston portion 63 reach bottom dead center, the volumes of the first air chamber 45 and the liquid chamber 47 become minimum. When the first piston portion 62 and the second piston portion 63 are located at bottom dead center, the biasing member 44 is pressed and compressed by the first seating surface portion 84 of the second piston portion 63.

[0128] After the nozzle unit 16 and the piston 42 have moved to the bottom dead center, the pressure on the nozzle unit 16 is released, thereby starting the preparation operation. When the pressure on the nozzle unit 16 is released, the compressed biasing member 44 expands due to its restoring force and biases the second piston portion 63 via the first seating surface portion 84. As a result, the nozzle unit 16 and the piston 42 move toward the top dead center. As the first piston portion 62 and the second piston portion 63 move toward the top dead center, the volumes of the first air chamber 45 and the liquid chamber 47 gradually increase.

[0129] When the first air chamber 45 increases, the air pressure in the first air chamber 45 becomes lower than atmospheric pressure. When the air pressure in the first air chamber 45 becomes lower than the air pressure in the second air chamber 46, the first on-off valve 93b is pressed by the air in the second air chamber 46 and moves in a direction away from the connecting portion 72, becoming open. At the same time, the second on-off valve 93c becomes closed. This allows the first air chamber 45 and the second air chamber 46 to communicate with each other, and the air in the second air chamber 46 flows into the first air chamber 45.

[0130] Furthermore, when the volume of the liquid chamber 47 increases, the pressure of the liquid medicine 200 in the liquid chamber 47 becomes lower than atmospheric pressure. When the second piston portion 63 moves toward top dead center, the second valve seat 83 and the valve body portion 92a come into contact. Therefore, the second valve body 92 is in a closed state. Then, when the pressure of the liquid medicine 200 in the liquid chamber 47 becomes lower than atmospheric pressure, the pressure of the liquid medicine 200 in the tube 4 separates the first valve body 91 from the first valve seat 55, and the first valve body 91 is in an open state. This allows the liquid medicine 200 in the container body 2 to flow into the liquid chamber 47.

[0131] Thereafter, when the first piston portion 62 and the second piston portion 63 reach the top dead center, the volumes of the first air chamber 45 and the liquid chamber 47 reach their maximums, thereby completing the preparation operation.

[0132] If the medicinal liquid 200 in the liquid chamber 47 after the preparatory operation has not reached the specified amount, the subsequent foam generation operation will not be able to discharge foam or will discharge an insufficient amount of medicinal liquid 200. In this case, for example, a pumping operation (priming) including the foam generation operation and the preparatory operation is repeated until the medicinal liquid 200 in the liquid chamber 47 after the preparatory operation reaches the specified amount, and the foam discharged by the subsequent foam generation operation is applied to the affected area of ​​the bedsore or damaged skin. [Example]

[0133] Examples of the present invention are described below: Three drugs were used: povidone-iodine, tretinoin, and trafermin.

[0134] [1] Example of using povidone-iodine as a drug [1-1] Material Drug: 10% (w / v) povidone-iodine solution (specific gravity: approximately 1.0) (Iwaki Pharmaceutical) Temperature-responsive polymer: Corifol P407 (abbreviation: P407) (BASF Japan) Solvent: Purified water Discharge container 1: Pump former (Daiwa Can Co., Ltd., F7 type, mesh 100 / 100) Discharge container 2: Aerosol can (Yamato Can Co., Ltd., aluminum monoblock can)

[0135] [1-2] Preparation of the drug solution in the discharge container Purified water was added to a 10% povidone-iodine solution, and Corifol P407 was added to this mixture in small amounts while stirring in an ice bath to avoid clumping, to prepare a drug solution containing 3% povidone-iodine by mass. The composition of the prepared drug solution is shown below.

[0136] [Table 1]

[0137] The liquid medicine was filled into a pump former to prepare a liquid medicine contained in a pump former, and on the other hand, the liquid medicine was filled into an aerosol can to prepare a liquid medicine contained in an aerosol can.

[0138] [1-3] Evaluation method (pH of the chemical solution) The pH of the chemical solution was measured using a pH meter (desktop pH meter F-71, HORIBA). The chemical solution at 5°C was used for pH measurement.

[0139] (Viscosity of the chemical solution) The viscosity of the liquid was measured using a B-type viscometer (TVB-10 viscometer, Toki Sangyo Co., Ltd.). The liquid was at 5°C for viscosity measurement. The measurement was performed using an L / A rotor at a rotation speed of 3.0 rpm.

[0140] (Foam density of the drug solution in foam form) The drug solution was dispensed in the form of foam from the dispenser. The foam was then poured into a container of known volume (3.0 cm 3) was filled to the brim, and the mass of the foam was measured to calculate the foam density.

[0141] (Dynamic viscoelasticity of gel) The foam discharged from the discharge container and Ringer's solution were mixed in a mass ratio of 10:3 and stirred overnight to eliminate the foam. The resulting mixture was then left to stand overnight in a thermostatic bath at 37°C to gel. The storage modulus (G') and loss modulus (G") of the resulting gel were measured using a rheometer (Thermo Scientific HAAKE MARS40, Thermo Fisher Scientific), and the loss factor (tanδ = G" / G') was calculated.

[0142] The measurements were carried out under the following conditions. Frequency: 1Hz Distortion: 0.1% Gap: 1mm Temperature: 37℃.

[0143] As a comparative example, a gel was prepared in the same manner as above, except that iodine coated ointment (Teikoku Pharmaceuticals) was used instead of the foam discharged from the discharge container, and the dynamic viscoelasticity of the gel was measured.

[0144] (Gel spreadability) The spreadability of the gel obtained according to the above procedure was measured using a parallel plate viscometer (Spreadmeter 419, Rigosha Co., Ltd.) to determine the yield value S0 [dyn / cm 2 Specifically, the evaluation was carried out by calculating the 3 The sample diameter D [cm] was measured visually, and the diameter D at the final measurement point after 60 seconds was ∞ [cm] to yield value S0 [dyn / cm 2 ] was calculated.

[0145] Yield value S0=48PVG / π 2 ×D ∞ 5 G: Gravitational acceleration (980cm / s 2 ) P: Mass of the glass plate (115.4g) V: sample volume (0.5 cm 3 ) D ∞ :Diameter at the final measurement point (cm) Measurements were performed at a temperature of 25±2°C and a humidity of 49-71%.

[0146] (gel adhesion) The adhesiveness of the gel obtained according to the above procedure was evaluated using a texture analyzer (TENSIPRESSER MyBoy2 SYSTEM, Taketomo Electric Co., Ltd.). Specifically, the gel was filled into an aluminum cup, and a breaking strength test was performed using a plunger (diameter 30 mm). The measurement was performed under the following conditions. Clearance: 0.5mm Compression speed: 2mm / s Pulling speed: 2mm / s.

[0147] [1-4] Evaluation results (pH and viscosity of the chemical solution) The measurement results of the pH and viscosity of the chemical solution are shown below.

[0148] [Table 2]

[0149] The pH of the drug solution was weakly acidic. The concentration of the temperature-responsive polymer in the drug solution had almost no effect on the pH of the drug solution. However, as the concentration of the temperature-responsive polymer in the drug solution increased, the viscosity of the drug solution tended to increase.

[0150] (Foam density of the drug solution in foam form) The measurement results of the bubble density of the chemical solution discharged from the discharge container are shown below.

[0151] [Table 3]

[0152] Foam density is 0.13~0.39g / cm 3This is within the range of foam density generally defined as foam (0.1 to 0.5 g / cm). 3 ) was within.

[0153] (Dynamic viscoelasticity of gel) The results of measuring the dynamic viscoelasticity of the gel are shown below.

[0154] [Table 4]

[0155] When any of the medicinal solutions 1A, 1B, and 1C was used, the storage modulus (G') was greater than the loss modulus (G"). Furthermore, the storage modulus (G') of each of the medicinal solutions 1A, 1B, and 1C was greater than that of the iodine-coated ointment (G'). The loss factors of the medicinal solutions 1A, 1B, and 1C were in the range of 0.02 to 0.27, which was smaller than that of the iodine-coated gel formed using the iodine-coated ointment. These results indicate that the medicinal solution of the present invention formed a gel with predominantly solid properties compared to the iodine-coated gel formed using the iodine-coated ointment. Furthermore, the results of the foam density and dynamic viscoelasticity indicate that the medicinal solution of the present invention can be dispensed onto the affected area in the form of a foam and subsequently gelled at temperatures near body temperature.

[0156] (Gel spreadability) The results of measuring the spreadability of the gel are shown below.

[0157] [Table 5]

[0158] The smaller the yield value, the softer and more easily spreadable the gel. When using any of medicinal solutions 1A, 1B, and 1C, the yield value was smaller than when using iodine-coated ointment. These results indicate that the medicinal solution of the present invention formed a gel that was softer and more easily spreadable than iodine-coated ointment. From these results, it is believed that the gel formed by the medicinal solution of the present invention is more likely to follow the movement of the affected area.

[0159] (gel adhesion) The results of measuring the adhesiveness of the gel are shown below.

[0160] [Table 6]

[0161] When any of the drug solutions 1A, 1B, and 1C was used, the adhesiveness values ​​were smaller than when iodine-coated ointment was used. These results indicate that the drug solutions of the present invention formed gels with lower adhesiveness than iodine-coated ointment.

[0162] [2] Example of using tretinoin as a drug The following experiment was carried out in the same manner as above, except that tretinoin was used instead of povidone-iodine.

[0163] [2-1] Material Drug: Tretinoin (Tokyo Chemical Industry Co., Ltd.) Temperature-responsive polymer: Corifol P407 (abbreviation: P407) (BASF Japan) Solvent: Purified water Discharge container 1: Pump former (Daiwa Can Co., Ltd., F7 type, mesh 100 / 100) Discharge container 2: Aerosol can (Yamato Can Co., Ltd., aluminum monoblock can)

[0164] [2-2] Preparation of the drug solution in the discharge container A drug solution containing 0.25% by mass of tretinoin was prepared according to the same procedure as described in section [1-2]. The composition of the prepared drug solution is shown below.

[0165] [Table 7]

[0166] The liquid medicine was filled into a pump former to prepare a liquid medicine contained in a pump former, and on the other hand, the liquid medicine was filled into an aerosol can to prepare a liquid medicine contained in an aerosol can.

[0167] [2-3] Evaluation method Each evaluation was carried out according to the same procedures as those described in [1-3].

[0168] [2-4] Evaluation results (pH and viscosity of the chemical solution) The measurement results of the pH and viscosity of the chemical solution are shown below.

[0169] [Table 8]

[0170] The pH of the drug solution was neutral. The concentration of the temperature-responsive polymer in the drug solution had almost no effect on the pH of the drug solution. However, as the concentration of the temperature-responsive polymer in the drug solution increased, the viscosity of the drug solution tended to increase.

[0171] (Foam density of the drug solution in foam form) The measurement results of the bubble density of the chemical solution discharged from the discharge container are shown below.

[0172] [Table 9]

[0173] Foam density is 0.12~0.36g / cm 3 This is within the range of foam density generally defined as foam (0.1 to 0.5 g / cm).3 ) was within.

[0174] (Dynamic viscoelasticity of gel) The results of measuring the dynamic viscoelasticity of the gel are shown below.

[0175] [Table 10]

[0176] When any of the medicinal solutions 2A, 2B, and 2C was used, the storage modulus (G') was greater than the loss modulus (G"). Furthermore, the storage modulus (G') of all of the medicinal solutions 2A, 2B, and 2C was greater than the storage modulus (G') of iodine-coated ointment. The loss factors of the medicinal solutions 2A, 2B, and 2C were in the range of 0.01 to 0.09, which was smaller than when iodine-coated ointment was used. These results indicate that the medicinal solutions of the present invention formed a gel in which the properties of a solid were predominant, compared to iodine-coated ointment. Furthermore, the results of foam density and dynamic viscoelasticity show that the medicinal solution of the present invention can be discharged to the affected area in the form of a foam and then gelled at a temperature close to body temperature.

[0177] (Gel spreadability) The results of measuring the spreadability of the gel are shown below.

[0178] [Table 11]

[0179] The smaller the yield value, the softer and more easily spreadable the gel. When using any of medicinal solutions 2A, 2B, and 2C, the yield value was smaller than when using iodine-coated ointment. These results indicate that the medicinal solution of the present invention formed a gel that was softer and more easily spreadable than iodine-coated ointment. From these results, it is believed that the gel formed by the medicinal solution of the present invention is more likely to follow the movement of the affected area.

[0180] (gel adhesion) The results of measuring the adhesiveness of the gel are shown below.

[0181] [Table 12]

[0182] When any of the drug solutions 2A, 2B, and 2C was used, the adhesiveness values ​​were smaller than when iodine-coated ointment was used. These results indicate that the drug solutions of the present invention formed gels with lower adhesiveness than iodine-coated ointment.

[0183] [3] Example of using trafermin as a drug The following experiment was carried out in the same manner as above, except that trafermin was used instead of povidone-iodine.

[0184] [3-1] Material Drug: Fiblast Spray freeze-dried product (i.e., Trafermin) (Kaken Pharmaceutical Co., Ltd.) Temperature-responsive polymer: Corifol P407 (abbreviation: P407) (BASF Japan) Solvent: Purified water Discharge container 1: Pump former (Daiwa Can Co., Ltd., F7 type, mesh 100 / 100) Discharge container 2: Aerosol can (Yamato Can Co., Ltd., aluminum monoblock can)

[0185] [3-2] Preparation of the drug solution in the discharge container A drug solution containing 0.00025% by mass of trafermin was prepared according to the same procedure as described in section [1-2]. The composition of the prepared drug solution is shown below.

[0186] [Table 13]

[0187] The liquid medicine was filled into a pump former to prepare a liquid medicine contained in a pump former, and on the other hand, the liquid medicine was filled into an aerosol can to prepare a liquid medicine contained in an aerosol can.

[0188] [3-3] Evaluation method Each evaluation was carried out according to the same procedures as those described in [1-3].

[0189] [3-4] Evaluation results (pH and viscosity of the chemical solution) The measurement results of the pH and viscosity of the chemical solution are shown below.

[0190] [Table 14]

[0191] The pH of the drug solution was neutral. The concentration of the temperature-responsive polymer in the drug solution had almost no effect on the pH of the drug solution. However, as the concentration of the temperature-responsive polymer in the drug solution increased, the viscosity of the drug solution tended to increase.

[0192] (Foam density of the drug solution in foam form) The measurement results of the bubble density of the chemical solution discharged from the discharge container are shown below.

[0193] [Table 15]

[0194] Foam density is 0.12~0.34g / cm 3 This is within the range of foam density generally defined as foam (0.1 to 0.5 g / cm). 3 ) was within.

[0195] (Dynamic viscoelasticity of gel) The results of measuring the dynamic viscoelasticity of the gel are shown below.

[0196] [Table 16]

[0197] When any of the medicinal solutions 3A, 3B, and 3C was used, the storage modulus (G') was greater than the loss modulus (G"). Furthermore, the storage modulus (G') of all of the medicinal solutions 3A, 3B, and 3C was greater than the storage modulus (G') of iodine-coated ointment. The loss factors of the medicinal solutions 3A, 3B, and 3C were in the range of 0.02 to 0.07, which was smaller than when iodine-coated ointment was used. These results indicate that the medicinal solutions of the present invention formed a gel that was predominantly solid in properties compared to iodine-coated ointment. Furthermore, the results of foam density and dynamic viscoelasticity show that the medicinal solution of the present invention can be dispensed onto the affected area in the form of a foam and then gelled at temperatures near body temperature.

[0198] (Gel spreadability) The results of measuring the spreadability of the gel are shown below.

[0199] [Table 17]

[0200] The smaller the yield value, the softer and more easily spreadable the gel. When using any of medicinal solutions 3A, 3B, and 3C, the yield value was smaller than when using iodine-coated ointment. These results indicate that the medicinal solution of the present invention formed a gel that was softer and more easily spreadable than iodine-coated ointment. From these results, it is believed that the gel formed by the medicinal solution of the present invention is more likely to follow the movement of the affected area.

[0201] (gel adhesion) The results of measuring the adhesiveness of the gel are shown below.

[0202] [Table 18]

[0203] When any of the drug solutions 3A, 3B, and 3C was used, the adhesiveness values ​​were smaller than when iodine-coated ointment was used. These results indicate that the drug solutions of the present invention formed gels with lower adhesiveness than iodine-coated ointment.

[0204] The present invention is not limited to the above-described embodiments, and various modifications can be made in the implementation stage without departing from the spirit of the invention. Furthermore, the embodiments may be implemented in appropriate combinations, in which case the combined effects can be obtained. Furthermore, the above-described embodiments include various inventions, and various inventions can be extracted by combining selected elements from the disclosed elements. For example, if the problem can be solved and the desired effect can be obtained even if some elements are deleted from all elements shown in the embodiments, the configuration from which these elements are deleted can be extracted as an invention. [Explanation of symbols]

[0205] 100...Discharge container, 200a...Medicinal solution in liquid form, 200b...Medicinal solution in foam form, 200c...Gelated medical solution, 300a...Epidermis, 300b...Dermis, 300c...Subcutaneous tissue, 300d...Muscle, 300e...Bone, 400...Pocket, 400a...Recess, 1...discharge container, 2...container body, 3...discharge device, 4...pipe, 10A...chemical solution contained in discharge container, 10B...chemical solution contained in discharge container, 11...first fixing portion, 12...male screw portion, 15...support member, 16...nozzle unit, 17...pump unit, 18...porous body, 18a...holder, 18b...first mesh, 18c...second mesh, 21...first fixed portion, 22...first guide portion, 23...second fixing portion, 25...female screw portion, 31...outer cylinder portion, 32...inner cylinder portion, 33...top plate portion, 34...discharge flow path, 35...first flow path portion, 36...nozzle portion, 39...second flow path portion, 41...cylinder unit, 42...piston, 43...valve portion, 44...urging member, 45...first air chamber, 46...second air chamber, 47...liquid chamber, 48...mixing chamber, 51...first cylinder portion, 51a...through hole, 52...second cylinder portion, 52a...seat surface, 53...second fixed portion, 53a...sealing member, 53b...flange portion, 54...mounting portion, 55...first valve seat, 61...rod portion, 62...first piston portion, 63...second piston portion, 65...first fitting portion, 65a...projection portion, 66...mixing portion, 66a ...through hole, 66b...projection portion, 67...second fitting portion, 71...first sliding portion, 71a...body portion, 71b...end portion, 72...connecting portion, 73...through hole, 74...groove, 81...second fitted portion, 82...second sliding portion, 83...second valve seat, 84...first seating surface portion, 85...third valve seat, 91...first valve body, 92...second valve body, 92a...valve body portion, 92b...shaft body, 92c...projection portion, 93...third valve body, 93a...fixed body, 93b...first on-off valve, 93c...second on-off valve, 94...second guide portion, 94a...second seating surface portion, 94b...slit, 94c... Projection portion, 101...discharge container, 102...container body, 103...discharge device, 104...pipe, 118...porous body, 118a...holder, 118b...first mesh, 118c...second mesh, 143...first support member, 143a...first through hole, 143b...second through hole, 143c...third through hole, 148...mixing chamber, 149...projection piece, 154...second support member, 161...third support member, 161a...fourth through hole, 193...valve body, 193a...fixed body, 193b...first on-off valve, 193c...second on-off valve, 200...chemical solution.

Claims

1. A medicinal solution for treating bedsores or damaged skin, comprising: a medicament for treating pressure sores or damaged skin; a temperature-responsive polymer that causes the medicinal solution to gel when exposed to the body temperature of the affected area; Solvent and a medicinal solution for application to the affected area in the form of a foam, comprising:

2. 2. The drug solution according to claim 1, wherein the temperature-responsive polymer is at least one selected from the group consisting of pluronic surfactants, polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymers, poly(N-alkylacrylamide), polyethylene glycol block copolymers, hydroxypropylmethylcellulose, methylcellulose, and a mixture of poly(ethylene glycol) and chitosan.

3. The chemical solution according to claim 1 , wherein the temperature-responsive polymer is contained in the chemical solution at a concentration in the range of 12.5 to 31.0 mass %.

4. The medicinal solution according to claim 1 , wherein the medicinal agent is a medicinal agent for treating bedsores.

5. The drug solution according to claim 1, wherein the drug is at least one selected from the group consisting of an antibacterial agent and a cell growth promoter.

6. The medicinal solution according to any one of claims 1 to 5, wherein the medicinal solution is a medicinal solution for treating bedsores.

7. a medicament for treating pressure sores or damaged skin; a temperature-responsive polymer that causes the medicinal solution to gel when exposed to the body temperature of the affected area; Solvent and a medicinal solution for treating bedsores or damaged skin, comprising: a discharge container that stores the liquid medicine and discharges the liquid medicine in the form of foam; The medicinal solution in a discharge container is used to apply the medicinal solution in the form of foam to an affected area.

8. The foam is 0.1 to 0.5 g / cm ３ The liquid medicine contained in the dispensing container according to claim 7, which is dispensed with a foam density within the range of 1000 to 10000.

9. The medicinal solution in a discharge container according to claim 7, wherein the temperature-responsive polymer is at least one selected from the group consisting of Pluronic surfactants, polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymers, poly(N-alkylacrylamide), polyethylene glycol block copolymers, hydroxypropylmethylcellulose, methylcellulose, and a mixture of poly(ethylene glycol) and chitosan.

10. 8. The chemical solution in a discharge container according to claim 7, wherein the temperature-responsive polymer is contained in the chemical solution at a concentration in the range of 12.5 to 31.0% by mass.

11. The medicinal liquid in a discharge container according to claim 7, wherein the medicinal liquid is a medicinal liquid for treating bedsores.

12. 8. The medicinal solution in a discharge container according to claim 7, wherein the medicinal agent is at least one selected from the group consisting of an antibacterial agent and a cell growth promoter.

13. 13. The liquid medicine in a dispensing container according to claim 7, wherein the liquid medicine is a liquid medicine for treating bedsores.

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