JP2014195626A - Nsaids-containing liquid drug - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an NSAIDs-containing liquid drug that enables an NSAIDs-containing internal fluid to be administered in a constant quantity by a simple operation, without bringing a container into contact with the affected part.SOLUTION: An NSAIDs-containing internal fluid is infilled into a pump spray container comprising a container body, an attachment cap, a pump dispenser, and a push-down head. Thus, an NSAIDs-containing liquid drug can be administered in a constant quantity by a simple operation, without bringing the container into contact with the affected part.

Description

  The present invention relates to an external liquid preparation that can administer a predetermined amount of an internal solution containing non-steroidal anti-inflammatory drugs (NSAIDs) without touching the affected area with a simple operation. About. More specifically, the present invention fills a pump spray container composed of a container main body, a mounting cap, a pump dispenser, and a push-down head with an internal solution containing NSAIDs, so that the container does not contact the affected part, and a certain amount. Is a liquid preparation containing NSAIDs that can be administered with a simple operation.

  In recent years, due to the rise in health consciousness, the population who performs light exercise such as walking, jogging and hiking is increasing. Light exercise increases health, but carries the risk of a fall accident, especially in older people with weakness in the legs and hips. These elderly people may suffer from musculoskeletal pain such as joint pain when a fall accident occurs. As for musculoskeletal pain, a cane or the like is sometimes used during walking, which causes a great hindrance to daily life such as walking, and therefore requires prompt treatment.

  The treatment of musculoskeletal pain is centered on the removal of pain by drugs, and NSAIDs are generally used as the first-line drug. NSAIDs were originally developed as oral preparations, and rapidly exhibit excellent anti-inflammatory analgesic effects. Therefore, NSAIDs are widely used for various pains including musculoskeletal pain.

  On the other hand, NSAIDs-containing oral preparations are known to cause side effects such as gastrointestinal disorders when used over a long period of time. In addition, when NSAIDs are used for a disease in which the affected area is local, such as musculoskeletal pain, more efficient treatment can be expected by selectively distributing the drug locally in the affected area. Therefore, NSAIDs-containing dosage forms that can avoid side effects such as gastrointestinal disorders and achieve selective drug distribution to the affected area have been desired for the treatment of musculoskeletal pain. Against this background, the route of administration of oral preparations was changed, and external preparations containing NSAIDs were developed.

  NSAIDs-containing external preparations are broadly classified into external application agents such as liquid agents disclosed in Patent Document 1 and external adhesive patches such as tape agents disclosed in Patent Document 2, and are used properly taking advantage of each advantage. It has been. An external application agent is less likely to be removed when administered to a joint or the like than an external patch, and has an advantage that drug delivery is not impaired. In particular, the liquid is superior in that the affected area does not become sticky after administration compared to other external preparations, so it is preferred for the treatment of musculoskeletal pain, but like other external preparations, Since it was necessary to administer the internal solution from the container, there was discomfort such as remaining in the hand. This unpleasant feeling is solved by filling a container provided with an application part with an internal solution and impregnating the application part with the internal solution, and using a liquid agent that can be administered to the affected part.

  However, this solution was not satisfactory in terms of the points described below because the application part directly contacts the affected part at the time of administration. That is, since the application part is contaminated by sweat, sebum, skin resident bacteria, etc., the cleanliness of the application part and the internal solution is impaired. In addition, when administered to a swollen affected area, it may be accompanied by severe pain due to physical stimulation of the application area. As described above, the contact of the application part with the affected part impairs cleanliness and, in some cases, causes severe pain, resulting in a decrease in feeling of use.

  Furthermore, it is difficult to adjust the amount of the internal solution impregnated in the coating part of this liquid agent, and there is a problem that a desired constant amount cannot be administered by a simple operation. Therefore, the user of this solution cannot easily grasp the dose, and there is a risk of causing side effects when an excessive amount is administered.

  Therefore, it has been desired to develop an NSAIDs-containing liquid agent that can administer a predetermined amount of an internal solution containing NSAIDs by a simple operation without causing the container to contact the affected part.

JP-A-6-199701 JP 2009-280509 A JP 2001-309986 A

  The object of the present invention has been made in view of the above-described circumstances, and provides an NSAIDs-containing liquid agent that can administer a predetermined amount of an internal solution containing NSAIDs by a simple operation without the container contacting the affected area. That is.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have filled a specific pump spray container with an internal solution containing NSAIDs, so that the container does not come into contact with the affected area, and a certain amount can be easily obtained. The present inventors have found that an NSAIDs-containing liquid that can be administered by operation can be obtained, and based on this finding, the present invention has been completed. That is, this invention is shown to the following (1)-(7).
(1) An internal liquid containing NSAIDs, which is an external liquid that can be administered in a simple amount with a simple operation without the container contacting the affected area,
The internal liquid is filled in a pump spray container composed of a container body, a mounting cap, a pump dispenser, and a push-down head,
The container body has an internal liquid filling space and an opened neck and neck,
A mounting cap has a ceiling wall portion with an opening at the center, a peripheral wall portion extending downward from the outer peripheral edge of the ceiling wall portion, and is disposed coaxially with the opening on the ceiling wall portion and facing upward. And a guide tube that guides the vertical movement of the push-down head,
The pump dispenser includes a cylinder, a piston member having a stem installed so as to be movable downward in an upward biased state, and a biasing member that biases the stem upward, and is filled through the mouth and neck of the container body. The piston member is built in the cylinder, the upper part of the stem protrudes upward from the upper end of the cylinder and the top wall of the mounting cap, and is disposed in the guide cylinder of the mounting cap. The cylinder has a mounting flange at the upper end, a pumping pipe at the lower end, and is attached to the mouth and neck of the container body with a mounting cap via packing,
The push-down head has a top wall portion, a mounting cylinder portion extending downward from the central portion of the lower surface of the top wall portion, and a mounting cylinder portion extending downward from the outer peripheral edge of the top wall portion. The outer peripheral wall part that surrounds from the outside in the direction and the spray port installed on the outer peripheral wall part, the mounting cylinder part has a function of fitting the upper end part of the stem, the spray port is an agar medium Without detecting bacteria that can form colonies in it,
The internal liquid is sprayed from the spray port through the conduction path formed inside by pushing the top wall portion of the depressing head and operating the pump dispenser, and the variation of the sprayed internal liquid amount is ± 10 of the standard. % NSAIDs-containing liquid agent, characterized by being not more than%.
(2) The NSAIDs-containing liquid according to (1) above, wherein the pump dispenser is an accumulator pump dispenser having an accumulator discharge valve.
(3) The NSAIDs-containing liquid according to (1) or (2) above, wherein the pump dispenser includes an adapter that enables operation in both an upright position and an inverted position.
(4) NSAIDs containing liquid agent in any one of said (1)-(3) whose capacity | capacitance of a container main body is 50-150 mL.
(5) The NSAIDs-containing liquid agent according to any one of (1) to (4), wherein the shape of the cross section of the container body is an oval shape.
(6) The NSAIDs-containing liquid agent according to any one of the above (1) to (5), wherein the amount of the internal liquid sprayed when the pump dispenser is operated once is 0.05 to 0.5 mL.
(7) When the pump dispenser is operated once and the internal liquid is sprayed toward a vertical plate surface 10 cm away, the maximum diameter of the wet portion on the plate surface is 5 cm to 30 cm, and the wet portion area is ^{10cm 2 ~700cm 2, (1)} NSAIDs containing liquid according to any one of the - (6).

  As described above, the present invention can provide an NSAIDs-containing liquid agent that can administer a predetermined amount of an internal solution containing NSAIDs by a simple operation without the container contacting the affected area.

It is the figure which showed the structural example of the NSAIDs containing liquid agent of this invention.

  Hereinafter, the NSAIDs-containing liquid agent of the present invention will be described in more detail with reference to the drawings. FIG. 1 schematically shows a configuration example of the NSAIDs-containing liquid agent of the present invention. Note that the examples described in the present specification do not particularly limit the present invention.

  The “cleanliness” of the present invention refers to the number of bacterial colonies (cfu :) observed with the naked eye after bringing the NSAIDs-containing liquid spray or application part into contact with a Luria-Bertani agar medium and leaving the agar medium at 37 ° C. for 24 hours. The determination was made by “cylony forming unit”. That is, when no colonies were observed, the container or internal solution after administration was “clean”, and when the number of colonies of 1 cfu or more was observed, the container or internal fluid after administration was “clean. It was not. "

  “Pain” of the present invention means suffering or pain caused by physical stimulation when an internal solution is administered to an affected area using a NSAIDs-containing solution. If the total score of the five subjects was less than 5 points when the pain was evaluated with a 5-level pain score, it was “no pain”, and if it was 5 points or more, “pain” With ".

  The “certain amount” of the present invention was determined by the relative standard deviation of the amount of the administered internal solution when five subjects administered the internal solution once per person using the NSAIDs-containing solution. That is, when the relative standard deviation was 0.1 or less, it was determined that “a certain amount could be administered”, and when it exceeded 0.1, “a certain amount could not be administered”.

  The NSAIDs-containing liquid agent of the present invention is one in which the internal liquid 1 is filled in a pump spray container. The pump spray container used in the present invention includes a container body A, a mounting cap B, a pump dispenser C, and a push-down head D.

  The material of the container body A, the mounting cap B, the pump dispenser C, and the push-down head D used in the present invention is, for example, polypropylene (PP), polyethylene (high density polyethylene: HDPE, low density polyethylene: LDPE), polyethylene terephthalate (PET) , Plastics such as polystyrene, metals such as aluminum, glass and the like can be used, and these can be used alone or in combination of two or more.

  The container main body A has a filling space for the internal liquid 1 and an open neck portion 2 on the inside. The mouth and neck 2 is provided with a screw 3 on the outer periphery. The shape of the container body A is not particularly limited, but a shape that is difficult to roll when rolled over is preferable from the viewpoint of preventing loss. That is, the container body A preferably has an oval cross-sectional shape or a shape having one or more corners. Further, considering the ease of holding the container, the container body A is particularly preferably oval. Moreover, the capacity | capacitance of the container main body A is although it does not restrict | limit in particular, If it is less than 50 mL, it is economically not preferable, and since a container is bulky and lacks portability when it exceeds 150 mL, it is preferable that it is 50-150 mL.

  The mounting cap B is disposed coaxially with the opening on the ceiling wall 4 having an opening at the center, the peripheral wall 5 extending downward from the outer peripheral edge of the ceiling wall 4, and the ceiling 4. And a guide tube 6 that extends upward and guides the vertical movement of the push-down head D. The peripheral wall portion 5 has a thread portion formed on the inner peripheral surface.

  The pump dispenser C includes a cylinder C1, a piston member C2 having a stem 7 built in the cylinder C1 and movably moved downward in an upward biased state, and a biasing member that biases the stem 7 upward. And is suspended in the filling space through the mouth neck 2 of the container body A. The upper portion of the stem 7 protrudes upward from the upper end of the cylinder C1 and the top wall 4 of the mounting cap B, and is disposed in the guide tube 6 of the mounting cap B. The cylinder C1 is provided with an attachment flange 8 at the upper end, and is attached to the mouth neck portion 2 of the container body A by screw engagement with a mounting cap B through a packing. A pumping pipe 9 is provided at the lower end of the cylinder C1. The pumping pipe 9 is arranged in the vicinity of the bottom surface of the container main body A.

  The push-down head D includes a top wall portion 10, a mounting cylinder portion extending downward from the center portion of the lower surface of the top wall portion 10, and a mounting portion extending downward from the outer peripheral edge of the top wall portion 10. The outer peripheral wall part 11 which surrounds a cylinder part from the radial direction outer side, and the spraying port 12 installed in the outer peripheral wall part 11 are provided. The mounting cylinder portion has a function of fitting the upper end portion of the stem 7. The outer diameter of the outer peripheral wall portion 11 is smaller than the inner diameter of the guide tube 6 of the mounting cap B. Therefore, the outer peripheral wall portion 11 can move up and down in the guide tube 6 as the push-down head D moves up and down. The spray port 12 communicates with the inside of the stem 7 through the inside of the outer peripheral wall portion 11. When the top wall portion 10 is pushed in, the pump dispenser C is activated, and the internal liquid 1 is sprayed from the spray port 12 through a conduction path formed inside.

  The pump dispenser C only needs to be capable of spraying a predetermined amount of the internal liquid 1 from the spray port 12 in accordance with the vertical movement of the push-down head D. That is, it is a general mechanism that includes a piston, a spring, and the like connected to the stem 7 and sucks, compresses, and pumps the internal liquid 1 through the pumping pipe 9, but is preferably disclosed in Japanese Patent No. 3614599. This is a pressure-accumulating pump dispenser equipped with a simple pressure-accumulating discharge valve. The accumulator pump dispenser has a mechanism capable of operating the pump dispenser C by moving the push-down head D up and down, and spraying a predetermined amount of the internal liquid 1 from the spray port 12 only at a liquid pressure equal to or higher than a predetermined pressure. Therefore, it is suitable when it is necessary to strictly manage the dose of NSAIDs.

  The NSAIDs-containing solution of the present invention may be used in an upright state or an inverted state depending on the administration site. Therefore, it is preferable to provide the pump dispenser C with an adapter that can be operated in both upright and inverted positions, as disclosed in JP-A-11-197562.

  The NSAIDs-containing liquid agent of the present invention can be equipped with an overcap E for the purpose of maintaining the cleanliness of the spray port 12. Since the overcap E only needs to cover the spray port 12, the overcap E may cover only the spray port 12, or may cover the spray port 12 and the push-down head D. In addition, the mounting cap B may be obscured, or the spray port 12, the push-down head D, the mounting cap B, and the container body A may be obscured. The attachment method can be freely selected from undercut engagement, screw engagement, or the like, and it is only necessary that the attachment method is detachably fixed. Examples of the material of the overcap E include PP, HDPE, LDPE, PET, polystyrene and other metals, metals such as aluminum, glass, and the like, and these can be used alone or in combination of two or more.

The NSAIDs-containing liquid preparation of the present invention is not particularly limited in the spray characteristics such as the amount of sprayed internal liquid, the shape and area of the sprayed internal liquid, and can be appropriately changed by adjusting the diameter of the spray port 12 and the like. Can do. However, if the amount of the internal liquid sprayed when the pump dispenser C is operated once is less than 0.05 mL, sufficient anti-inflammatory analgesic effect cannot be obtained, and if it exceeds 0.5 mL, Since the container main body A becomes large with increasing surface area and lacks portability, it is preferably 0.05 to 0.5 mL. Furthermore, since the NSAIDs-containing liquid preparation of the present invention is used for joint pain and the like, it is preferable that the internal liquid 1 is sprayed over the entire joint when the pump dispenser C is operated once. Therefore, when the internal liquid 1 is sprayed toward a vertical plate surface separated by 10 cm, the maximum diameter of the wet portion on the plate surface is 5 cm to 30 cm, and the area of the wet portion is 10 cm ^{2 to} 700 cm ² . Preferably there is. When the area of the wet portion is less than 10 cm ² , spraying cannot be performed in a desired range, and when the area exceeds 700 cm ² , spraying occurs outside the desired range and waste is generated, which is not preferable.

  Examples of NSAIDs used in the present invention include indomethacin, ibuprofen, ketoprofen, ibuprofen piconol, piroxicam, aspirin, felbinac, alclofenac, clidanac, salsalate, naproxen, fenbufen, flufenamic acid, flurbiprofen, methiadiic acid, mefenamic acid Examples thereof include acids, bendazac, bufexamac, ufenamate, loxoprofen and salts thereof, glycyrrhetinic acid and salts thereof, methyl salicylate, glycol salicylate and the like, and these can be used alone or in combination of two or more. If the content of NSAIDs is less than 0.01% by mass relative to the total amount of the internal solution, a sufficient anti-inflammatory analgesic effect cannot be obtained, and if it exceeds 5% by mass, the risk of developing side effects increases. Although it is preferable that it is 0.01-5 mass%, More preferably, it is 0.5-3.5 mass%.

  Examples of the alcohol used in the present invention include ethanol, absolute ethanol, various denatured ethanol, n-propanol, i-propanol, n-butanol, i-butanol and the like, and can be used alone or in combination of two or more. . If the alcohol content is less than 10% by mass relative to the total amount of the internal solution, it is difficult to sufficiently dissolve or disperse NSAIDs, and if it exceeds 60% by mass, the skin irritation becomes high. Although it is preferable that it is 10-60 mass%, More preferably, it is 20-40 mass%.

  Examples of the water used in the present invention include purified water, sterilized water, natural water, normal water, and water for injection. These can be used alone or in combination of two or more, but purified water is preferred.

  The NSAIDs-containing liquid preparation of the present invention includes various components that are acceptable for producing pharmaceuticals within the range not impairing the effects of the present invention, that is, a surfactant, a thickener, a moisturizer, an oil component, a pH adjuster, a chelate. An agent, a fragrance / cooling agent, an antioxidant, an antiseptic, an absorption accelerator, and the like can be appropriately blended.

  Examples of the surfactant include ether compounds such as polyoxyethylene alkyl ether and polyoxyethylene polypropylene alkyl ether, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin. Fatty acid esters, polyethylene glycol fatty acid esters, ester compounds such as sucrose fatty acid esters, nonionic surfactants such as polyoxyethylene castor oil / hardened castor oil, polyoxyethylene polyoxypropylene polymer, and alkylbetaines such as lauryl dimethyl betaine , Amphoteric surfactants such as alkylamide betaines such as coconut oil fatty acid amidopropylbetaine, alkylsulfobetaines and imidazolines Agents, saturated higher fatty acid salts, alkyl sulfonates, alkyl ether sulfonates, anionic surfactants such as alkyl ether sulfonates and the like, may be used alone or in combination of two or more.

  Examples of the thickener include cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose, carmellose, croscarmellose and methylcellulose, modified starches such as partially pregelatinized starch, polyvinyl alcohol, polyvinylpyrrolidone, crospovidone, polyethylene glycol, carboxy Vinyl polymers, acrylic acid / alkyl methacrylate copolymers, xanthan gum, carrageenan, sodium alginate, gum arabic, guar gum, locust bean gum, pullulan, gelatin, sodium polyacrylate, etc. are used alone or in combination of two or more. be able to.

  Examples of humectants include ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, dibutylene glycol, glycerin, diglycerin, polyglycerin, sugars such as sucrose, lactose, maltose, mannitol, erythritol, and xylitol, and sugar alcohols. Can be used alone or in combination of two or more.

  Examples of the oil component include unsaturated fatty alcohols such as palmitooleyl alcohol, oleyl alcohol, eicosonyl alcohol, elaidyl alcohol, and linoleyl alcohol, oleic acid, elaidic acid, linoleic acid, undecylenic acid, myristoleic acid, Unsaturated fatty acids such as palmitoleic acid, lindelic acid, lauroleic acid, tuzuic acid, peteroceric acid, bassenic acid, gondoic acid, glyceryl monooleate glycerin, dioleate, octyldodecyl oleate, oleyl oleate Fatty acid esters, oleyl alcohol, elidyl alcohol liquid paraffin, petrolatum, hydrocarbons such as microcrystalline wax, methylpolysiloxane, methylphenylpolysiloxane, dimethyl Silicon oils such as cyclopolysiloxane, waxes such as beeswax, higher alcohols such as cetyl alcohol and stearyl alcohol, sterols such as cholesterol, octyldodecyl oleate, oleyl oleate, cetyl octanoate, isopropyl myristate, myristine Examples include fatty acid esters such as acid myristyl, and metal soaps such as aluminum stearate and magnesium stearate, which can be used alone or in combination of two or more.

  Examples of pH adjusters include acetic acid, formic acid, lactic acid, tartaric acid, oxalic acid, glycolic acid, malic acid, citric acid, succinic acid, fumaric acid, phosphoric acid, hydrochloric acid, nitric acid, sulfuric acid and their salts, sodium hydroxide , Potassium hydroxide, calcium hydroxide, arginine, methylamine, ethylamine, propylamine, dimethylamine, diethylamine, dipropylamine, trimethylamine, triethylamine, tripropylamine, monomethanolamine, monoethanolamine, monopropanolamine, dimethanol Amine, diethanolamine, dipropanolamine, trimethanolamine, triethanolamine, isopropanolamine, diisopropanolamine, tripropanolamine, aqueous ammonia, guanidine carbonate, sodium bicarbonate Um, such as ammonium carbonate and the like, it may be used alone or in combination of two or more.

  Examples of the chelating agent include pyrophosphoric acid, hexametaphosphoric acid, gluconic acid and the like, and can be used alone or in combination of two or more.

  Examples of fragrances and refreshing agents include mint oil, mint oil, cinnamon oil, clove oil, fennel oil, castor oil, turpentine oil, eucalyptus oil, orange oil, lavender oil, lemon oil, rose oil, lemongrass oil, Fragrances such as daikyo oil, chimian oil, henoposi oil, yamadine oil, touka oil, bergamot oil, citronella oil, camphor oil, geranium oil, and plant extracts such as rosemary and sage, l-menthol, camphor, Cooling agents such as thymol, N-ethyl-p-menthane-carboxamide, p-menthane-3,8-diol, l-isopulegol, l-menthyl glyceryl ether, and the like may be used alone or in combination of two or more. Can do.

  Examples of the antioxidant include ascorbic acid, propyl gallate, butylhydroxyanisole, dibutylhydroxytoluene, nordihydroguaiaretic acid, tocopherol, and tocopherol acetate, which can be used alone or in combination of two or more. .

  Examples of preservatives include thymol, isopropylmethylphenol, benzoic acid, methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, benzyl alcohol, benzalkonium chloride, benzethonium chloride, and the like. It can be used alone or in combination of two or more.

  Examples of the absorption promoter include diisopropyl adipate, lecithin, squalane, squalene, azone, l-menthol, polyethylene glycol, isopropyl myristate, dimethyl sulfoxide, peppermint oil, eucalyptus oil, d-limonene, dl-limonene and the like. These can be used alone or in combination of two or more.

  The internal solution used in the present invention may be in a uniform state in which the above-described components are mixed and dissolved, or may be in a state of being uniformly dispersed as a fine powder.

  The NSAIDs-containing liquid preparation of the present invention can be produced by a conventionally known conventional method or a method newly provided in the future. As typical methods, NSAIDs and alcohol are sufficiently dissolved or dispersed in purified water, and further surfactants, thickeners, moisturizers, oil components, pH adjusters, chelating agents, fragrances / cooling agents, Antioxidants, preservatives, absorption accelerators and the like are added and dissolved or dispersed sufficiently to prepare an internal solution. The prepared internal solution can be filled into a pump spray container to produce the NSAIDs-containing solution of the present invention.

  Next, the usage aspect of the NSAIDs containing liquid agent of this invention is demonstrated. First, when the top wall portion 10 of the push-down head D is pushed by hand, the stem 7 moves downward. Following the movement of the stem 7, the piston member C2 moves downward. Thereby, the internal liquid 1 in the cylinder C1 is compressed and enters the stem 7, and moves upward in the stem 7. Then, the internal liquid 1 is sprayed to the outside from the spray port 12 through the inside of the outer peripheral wall portion 11. Thereafter, when the hand is released from the top wall portion 10 of the push-down head D, the piston member C2 is restored and moved upward by the upward biasing force of the biasing member. Thereby, the inside of the cylinder C1 is depressurized, and the internal liquid 1 filled in the container main body A is sucked into the cylinder C1 through the pumping pipe 9.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
Example 1
Based on the formulation shown in Table 1, it was prepared by the method of Preparation Method 1 described later to obtain the NSAIDs-containing liquid agent 1 of the present invention. As a result of conducting a cleanliness confirmation test according to Test Example 1 using the obtained NSAIDs-containing solution 1, the containers or internal liquid after administration were clean in all subjects. The results are shown in Table 2. Next, as a result of conducting a pain confirmation test according to Test Example 2, the total score was 0, and no pain was caused at the time of administration. The results are shown in Table 3. Moreover, as a result of conducting a fixed amount confirmation test according to Test Example 3, the relative standard deviation was 0.01, and a fixed amount could be administered. Furthermore, in Test Example 3, the amount of internal fluid administered to all subjects was ± 10% of the standard. The results are shown in Table 4.

(Preparation method 1)
A pump spray container in which the internal liquid obtained by sequentially adding felbinac, ethanol and glycerin to purified water, stirring and dissolving, the capacity of the container body is 100 mL, and the amount of internal liquid sprayed at one time is 0.1 mL To obtain an NSAIDs-containing liquid agent.

(Test Example 1)
Cleanliness confirmation test Using the NSAIDs-containing solution 1 of Example 1 and the solution 1 of Comparative Example 1 described later, a cleanness confirmation test was performed by the following method. For 5 subjects suffering from musculoskeletal pain, the internal solution was administered to the affected area using each NSAIDs-containing solution. After administration, the spray port or application part was brought into contact with Luria-Bertani agar medium, and the agar medium was allowed to stand at 37 ° C. for 24 hours. After 24 hours, the agar medium was observed with the naked eye, and the number of bacterial colonies was counted. When no colonies were observed, the container or internal solution after administration was “clean”, and when the number of colonies was 1 cfu or more, the container or internal solution after administration was “not clean. " The results are shown in Table 2.

(Test Example 2)
Pain confirmation test Using the NSAIDs-containing solution 1 of Example 1 and the solution 1 of Comparative Example 1 described later, a pain confirmation test was performed by the following method. Five subjects suffering from musculoskeletal pain were asked to administer the internal fluid to the affected area using each NSAIDs-containing solution, and the pain or pain caused by physical stimulation at the time of administration was evaluated with a five-level pain score. I was asked to. An unbearable suffering or pain was given 5 points, and as it became 4, 3, 2, 1 points, the suffering or pain became weaker, and 0 points were given when there was no suffering or pain at all. When the total score of 5 subjects was less than 5 points, it was “no pain”, and when it was 5 points or more, it was “pained”. The results are shown in Table 3.

(Test Example 3)
Fixed amount confirmation test Using the NSAIDs-containing solution 1 of Example 1 and the solution 1 of Comparative Example 1 described later, a certain amount confirmation test was performed by the following method. For five subjects suffering from musculoskeletal pain in the thigh, a test area of the same size was provided in the thigh of each person, and the internal fluid was administered into the test area. The NSAIDs-containing solution 1 of Example 1 was administered to the entire test area by pushing the push-down head once. In addition, the liquid 1 of Comparative Example 1 was administered to the entire test area by reciprocating three times within the test area. The amount of the administered internal solution was calculated by dividing the weight difference of the NSAIDs-containing solution before and after the start of administration by the specific gravity. For each NSAIDs-containing solution, the average value, standard deviation, and relative standard deviation are calculated. If the relative standard deviation is 0.1 or less, it is determined that “a certain amount could be administered”. Was “a fixed dose could not be administered”. The results are shown in Table 4.

(Comparative Example 1)
In Example 1, the same preparation method as in Example 1 was repeated except that the container filled with the internal liquid was changed from a pump spray container to a container having an application part, whereby Liquid 1 was obtained. As a result of conducting a cleanliness confirmation test according to Test Example 1 using the obtained solution 1, the container or internal solution was not clean in 4 subjects. The results are shown in Table 2. Next, as a result of conducting a pain confirmation test according to Test Example 2, the total score was 19 points, accompanied by pain at the time of administration. The results are shown in Table 3. Moreover, as a result of conducting a fixed amount confirmation test according to Test Example 3, the relative standard deviation was 0.61, and a fixed amount could not be administered. The results are shown in Table 4.

  The present invention fills NSAIDs-containing internal solution into a pump spray container composed of a container body, a mounting cap, a pump dispenser, and a push-down head, so that the container does not come into contact with the affected area and a certain amount can be easily operated. It relates to a liquid preparation containing NSAIDs that can be administered and can be used industrially.

A Container body B Mounting cap C Pump dispenser C1 Cylinder C2 Piston member D Push-down head
E Overcap 1 Internal liquid 2 Neck part 3 Screw 4 Top wall part 5 Peripheral wall part 6 Guide tube 7 Stem 8 Mounting flange 9 Pumping pipe 10 Top wall part 11 Peripheral wall part 12 Spray port

Claims (7)

An internal liquid containing NSAIDs is an external liquid that can be administered in a simple amount by a simple operation without the container coming into contact with the affected area,
The internal liquid is filled in a pump spray container composed of a container body, a mounting cap, a pump dispenser, and a push-down head,
The container body has an internal liquid filling space and an opened neck and neck,
A mounting cap has a ceiling wall portion with an opening at the center, a peripheral wall portion extending downward from the outer peripheral edge of the ceiling wall portion, and is disposed coaxially with the opening on the ceiling wall portion and facing upward. And a guide tube that guides the vertical movement of the push-down head,
The pump dispenser includes a cylinder, a piston member having a stem installed so as to be movable downward in an upward biased state, and a biasing member that biases the stem upward, and is filled through the mouth and neck of the container body. The piston member is built in the cylinder, the upper part of the stem protrudes upward from the upper end of the cylinder and the top wall of the mounting cap, and is disposed in the guide cylinder of the mounting cap. The cylinder has a mounting flange at the upper end, a pumping pipe at the lower end, and is attached to the mouth and neck of the container body with a mounting cap via packing,
The push-down head has a top wall portion, a mounting cylinder portion extending downward from the central portion of the lower surface of the top wall portion, and a mounting cylinder portion extending downward from the outer peripheral edge of the top wall portion. The outer peripheral wall part that surrounds from the outside in the direction and the spray port installed on the outer peripheral wall part, the mounting cylinder part has a function of fitting the upper end part of the stem, the spray port is an agar medium Without detecting bacteria that can form colonies in it,
The internal liquid is sprayed from the spray port through the conduction path formed inside by pushing the top wall portion of the depressing head and operating the pump dispenser, and the variation of the sprayed internal liquid amount is ± 10 of the standard. % NSAIDs-containing liquid agent, characterized by being not more than%.   The NSAIDs-containing liquid agent according to claim 1, wherein the pump dispenser is an accumulator pump dispenser having an accumulator discharge valve.   The NSAIDs-containing liquid according to claim 1 or 2, wherein the pump dispenser includes an adapter that enables operation in both an upright position and an inverted position.   The NSAIDs-containing liquid agent according to any one of claims 1 to 3, wherein the container body has a capacity of 50 to 150 mL.   The NSAIDs-containing liquid agent according to any one of claims 1 to 4, wherein a shape of a cross section of the container main body is an oval shape.   The NSAIDs-containing liquid agent according to any one of claims 1 to 5, wherein when the pump dispenser is operated once, the amount of the internal liquid sprayed is 0.05 to 0.5 mL. When the pump dispenser is operated once and the internal liquid is sprayed toward a vertical plate surface 10 cm away, the maximum diameter of the wet portion on the plate surface is 5 cm to 30 cm, and the area of the wet portion is a 10cm ² ~700cm ^2, NSAIDs containing liquid according to any one of claims 1-6.

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