JP2014234377A - Salicylic acid-containing formulation and production method thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a formulation of a salicylic acid-containing external preparation which has a high quick-drying property, applicability and preservability and a production method thereof.SOLUTION: A salicylic acid-containing formulation is obtained by filling a tube container with a salicylic acid-containing external preparation comprising 10 to 20 mass% of salicylic acid, 8.25 to 9.4 mass% of pyroxylin, ether and ethanol. A production method of the salicylic acid-containing formulation comprises the steps of: (a) producing the salicylic acid-containing external preparation at the temperature of 5 to 35°C; (b) filling the tube container with the salicylic acid-containing external preparation under an atmosphere of the temperature of 30°C or less; and (c) sealing the tube container.

Description

  The present invention relates to a salicylic acid-containing preparation and a method for producing the same, and more particularly, to a salicylic acid-containing preparation using a salicylic acid-containing external preparation having a specific composition and a method for producing the same.

  As an external preparation for treating skin diseases such as corn, octopus and warts, a salicylic acid-containing external preparation containing antibacterial activity against microorganisms and containing salicylic acid having a keratin softening action is known.

  As a dosage form of a salicylic acid-containing external preparation, salicylic acid, which is a drug, is dissolved in a solution of nitrocellulose, also called collodion, also known as piroxylin, that is, nitrocellulose, dissolved in a mixed solvent of ether and ethanol. A liquid agent (hereinafter sometimes referred to as “salicylic acid solution”) is known. One of the characteristics of this solution is that it has a film-forming property, and when applied to the affected area, the solvent evaporates to form a film on the skin, and the drug salicylic acid stays in the affected area for a long time. For example, Patent Document 1 discloses a preparation in which salicylic acid, which is a remedy for uronome, is contained in a solution obtained by dissolving nitrocellulose (pyroxylin) in a mixture of ether and ethanol (that is, collodion). Yes.

  In Patent Document 2, instead of using a mixed solvent of ethanol and ether, piroxylin is dissolved in a mixed solvent of acetone and a lower alcohol, and a medicinal component such as salicylic acid is dissolved. An external preparation for skin having excellent adhesion is disclosed, and as an example, 95 g of salicylic acid is disclosed in collodion prepared by dissolving 55 g of pyroxylin in 900 ml of alcohol and 100 ml of acetone.

  In Patent Document 3, a mixed solvent of acetone and a lower alcohol is used as a solvent containing a drug such as salicylic acid, and a predetermined ratio of piroxylin and polyvinylpyrrolidone as a film forming agent, that is, 1 to 8% by weight of piroxylin, An external preparation for skin is disclosed that is formulated so that piroxylin / polyvinylpyrrolidone = 3.5 to 0.5. It is described that the external preparation for skin disclosed in Patent Document 3 does not feel sticky at the time of use, and is excellent in quick-drying and adhesiveness to the skin.

  On the other hand, in Patent Document 4, salicylic acid is contained in a solvent such as ethanol, isopropanol, methanol, acetone, diethyl ether and propylene glycol in an amount of 15% by weight or more, preferably about 20% by weight or more, more preferably about 25% by weight or more. A liquid agent for locally applying a concentrated salicylic acid solution is disclosed. Further, as a conventional technique, a plaster containing 40% salicylic acid and an ointment containing 50% salicylic acid are disclosed.

  In salicylic acid-containing preparations using salicylic acid-containing external preparations, and organic solvents used in collodion are often highly volatile, they are usually stored and used in a sealed container. Among them, ether, which is a widely used organic solvent, has high corrosiveness to various plastics, and thus a glass bottle has been used as a storage container for a salicylic acid-containing preparation which is a solution of collodion.

  That is, a salicylic acid-containing external preparation, specifically, a salidilic acid collodion solution is filled in a storage container, which is a glass bottle provided with a lid, and stored with the lid closed. When applying salicylic acid-containing external preparations to skin diseases such as sea urchins, octopuses, warts, etc., the lid is opened and it is usually made of a rod (glass or polyethylene) attached to the lid. In many cases, hereinafter, it may be referred to as an “application bar”), an appropriate amount of a salicylic acid-containing external preparation is attached to the affected area and applied to the affected area. The affected part softened by applying an external preparation several times a day and continuing this for several days can be immersed in hot water and excised.

  However, in order to use a salicylic acid-containing external preparation for glass bottle storage containers, it is necessary to open and close the glass bottle cover many times, so that the organic solvent contained in the collodion is volatilized and the wall surface of the glass bottle In some cases, it may solidify at the inside of the lid, the application bar, or the like, or in some cases, the salicylic acid-containing external preparation (salicylic acid solution) remaining in the container cannot be taken out.

  In addition, acetone, which may be used as an auxiliary agent or an organic solvent for dissolving salicylic acid, has extremely high degreasing properties and has an irritating odor. Therefore, it is considered preferable for safety not to be blended with a salicylic acid-containing external preparation. Has come to be.

  Therefore, it has a high quick-drying property, and it has excellent applicability such that it can be applied directly to the affected area without causing stickiness or dripping during use to form a film containing salicylic acid, and the solvent is volatilized during storage and use. Therefore, it has been desired to provide a preparation of a salicylic acid-containing external preparation that does not solidify and has excellent storage stability, and a method for producing the same.

JP 60-64921 JP 47-39621 JP-A-5-58914 Special table 2000-504689

  An object of the present invention is to provide a preparation of a salicylic acid-containing external preparation having a high quick-drying property and excellent in applicability and storage stability, and a method for producing the same.

  As a result of diligent research on solving the above-mentioned problems, the present inventor found that the salicylic acid-containing external preparation having a specific composition is filled in a tube container to obtain a salicylic acid-containing preparation, and the present invention can be solved. Completed the invention.

  That is, according to the present invention, there is provided a salicylic acid-containing preparation in which a tube container is filled with a salicylic acid-containing external preparation containing 10 to 20% by mass of salicylic acid, 8.25 to 9.4% by mass of pyroxylin, and ether and ethanol. Is done.

Moreover, according to this invention, the salicylic acid containing formulation of the following (1)-(4) is provided as an embodiment.
(1) The said salicylic acid containing formulation whose ratio (mass ratio) of ether and ethanol is 1: 1-4: 1.
(2) The above-mentioned salicylic acid-containing preparation which does not contain acetone.
(3) The above-mentioned salicylic acid-containing preparation which does not contain any thickener, gelling agent or filler.
(4) The said salicylic acid containing formulation whose tube container is a product made from aluminum and whose aperture diameter is 0.3-3 mm.

Furthermore, according to the present invention, the following steps (a) to (c):
(A) a step of producing a salicylic acid-containing external preparation at a temperature of 5 to 35 ° C;
(B) a step of filling a tube container with a salicylic acid-containing external preparation in an atmosphere at a temperature of 30 ° C. or lower; and (c) a step of sealing the tube container;
A method for producing the above-mentioned salicylic acid-containing preparation comprising

  According to the present invention, a salicylic acid-containing preparation containing 10 to 20% by mass of salicylic acid, 8.25 to 9.4% by mass of piroxylin and ether and ethanol is a salicylic acid-containing preparation filled in a tube container. In addition, there is an effect that it is possible to provide a preparation of a salicylic acid-containing external preparation that has high quick-drying properties and is excellent in applicability and storage stability.

Moreover, according to the present invention, the following steps (a) to (c):
(A) a step of producing a salicylic acid-containing external preparation at a temperature of 5 to 35 ° C;
(B) a step of filling a tube container with a salicylic acid-containing external preparation in an atmosphere at a temperature of 30 ° C. or lower; and (c) a step of sealing the tube container;
With the above-described method for producing a salicylic acid-containing preparation, it is possible to easily provide a preparation of a salicylic acid-containing external preparation that has high quick-drying properties and is excellent in applicability and storage stability.

I. Salicylic acid-containing external preparation The salicylic acid-containing external preparation used in the salicylic acid-containing preparation of the present invention contains 10 to 20% by mass of salicylic acid, 8.25 to 9.4% by mass of pyroxylin, ether, and ethanol. In addition to being highly dry, it has excellent applicability such that it can be applied directly to the affected area without causing stickiness or dripping during use to form a film containing salicylic acid.

1. Salicylic acid Salicylic acid contained in a salicylic acid-containing external preparation is antibacterial against microorganisms and has a keratin softening action, so that it is used to treat skin diseases such as corn, octopus and warts. . The content of salicylic acid in the salicylic acid-containing external preparation is 10 to 20% by mass, preferably 12 to 18% by mass, more preferably 13 to 17% by mass, where the total composition of the salicylic acid-containing external preparation is 100% by mass. It is. If the salicylic acid content in the salicylic acid-containing external preparation is too small, the therapeutic effect on skin diseases may be insufficient. If the salicylic acid content is too high, the applicability of the external preparation may decrease, the skin disease or the skin around the disease may be irritated, or redness may occur.

2. Piroxylin Piroxylin is a nitrocellulose having nitrate esters in up to three places per glucose unit of cellulose, and is called collodion or shiojirin. )) It is a film-forming component that forms a film on the skin by applying the solvent in the form of an organic solvent solution and then volatilizing the solvent. The content of piroxylin in the salicylic acid-containing external preparation is 8.25 to 9.4 mass%, preferably 8.3 to 9.3 mass%, with the total composition of the salicylic acid-containing external preparation being 100 mass%. More preferably, it is 8.4 to 9.2 mass%. The salicylic acid-containing external preparation according to the present invention is characterized in that the content of piroxylin is higher than that of the liquid and in a narrow concentration range. If the content of piroxylin in the salicylic acid-containing external preparation is too small, the ability to form a film is insufficient, the drug salicylic acid cannot remain in the affected area for a long time, and the therapeutic effect for skin diseases may be insufficient. Depending on the case, the liquid may sag and may not form a film on the skin. When there is too much content of piroxylin, the applicability | paintability of an external preparation will fall, depending on the case, liquid drainage will worsen and the favorable application | coating to the affected part on skin may become difficult.

3. Ether The salicylic acid-containing external preparation used in the salicylic acid-containing preparation of the present invention uses ether as an organic solvent for forming a collodion that dissolves salicylic acid, that is, an organic solvent solution of piroxylin. As the ether, ethers usually used in collodion can be used, and diethyl ether, methyl ethyl ether and the like can be used, but diethyl ether is preferably used.

4). Ethanol The salicylic acid-containing external preparation used in the salicylic acid-containing preparation of the present invention is a collodion that dissolves salicylic acid, that is, the point of using ethanol together with ether as an organic solvent for forming an organic solvent solution of pyroxylin, that is, ether and It is characterized in that a mixed solvent with ethanol is used. The salicylic acid-containing external preparation used in the present invention contains ether and ethanol. The ratio (mass ratio) of ether and ethanol in the mixed solvent of ether and ethanol is not particularly limited, but is usually 0.5: 1 to 5: 1, preferably 1: 1 to 4: 1, more preferably. Is in the range of 1.2: 1 to 3.7: 1, more preferably 1.5: 1 to 3.5: 1. If the ether ratio is too large, the salicylic acid-containing external preparation has a high film-forming property, which may easily stain clothes, may cause poor liquid drainage and decrease applicability, and may increase the volatility of the solvent. Storage stability may be reduced. If the ether ratio is too small, the quick-drying property is lowered and the film-forming property may be lowered.

5. Other components The salicylic acid-containing external preparation used in the present invention is composed of 10% by mass of salicylic acid and 8.25 to 9.4% by mass of pyroxylin, ether and Although it contains ethanol, it can further contain other components as desired. For example, the salicylic acid-containing external preparation used in the present invention includes, as other components, other organic solvents such as acetone, methanol, isopropanol, methyl ethyl ketone, thickeners, gelling agents, fillers, stabilizers, oxidizing agents. You may contain other additives, such as a chemical | medical agent applied to other skin, such as an inhibitor, antiseptic | preservative, a pigment, a coloring agent, and a fragrance | flavor. The content of these other organic solvents and other additives is appropriately determined within a range that does not impair the quick-drying property, coating property, and storage property of the salicylic acid-containing external preparation (usually within 10% by mass). be able to. Considering quick-drying properties, it is preferable not to contain any thickener, gelling agent or filler.

6). Salicylic acid-containing external preparation It is desirable that the salicylic acid-containing external preparation used in the present invention does not use an organic solvent other than ether and ethanol from the viewpoints of film formation of collodion and applicability of the external preparation. In particular, it is often preferable that the salicylic acid-containing external preparation used in the present invention does not contain acetone from the viewpoint of degreasing and irritating odors. Similarly, it is often preferable not to contain any thickener, gelling agent or filler from the viewpoint of quick drying. Therefore, the salicylic acid-containing external preparation used in the present invention contains 10 to 20% by mass of salicylic acid and 8.25 to 9.4% by mass of pyroxylin, and a mixed solvent of ether and ethanol as the remaining component. In the salicylic acid-containing preparation in which the salicylic acid-containing external preparation is filled in the tube container, the salicylic acid-containing external preparation is applied to the diseased part without causing dripping or poor liquid drainage. be able to.

  In the salicylic acid-containing preparation of the present invention, as the salicylic acid-containing external preparation filled in the tube container, the tube container can be filled, discharged from the tube container, applied to the diseased affected area, a film is formed, and salicylic acid is applied to the affected area. The dosage form is not limited as long as it can be kept for a long time. For example, it can be a semisolid preparation such as an ointment, cream, paste, or gel, and preferably is an ointment dosage form . In particular, from the viewpoint of good film-forming properties, oleaginous ointments are preferred, and oleaginous ointments composed only of salicylic acid, pyroxylin, ether and ethanol are more preferred. The oily ointment usually has a water content of 1% by mass or less so as not to intentionally contain water in the production process.

II. Salicylic acid-containing preparation The salicylic acid-containing preparation of the present invention comprises salicylic acid-containing external preparation containing 10 to 20% by mass of salicylic acid and 8.25 to 9.4% by mass of pyroxylin, ether and ethanol in a tube container. It is a formulation.

1. Tube container As the tube container used in the salicylic acid-containing preparation of the present invention, a tube container conventionally used in a semi-solid preparation such as an ointment, cream, paste, or gel can be used. The tube container is usually provided integrally with a tube container body filled with a salicylic acid-containing external preparation and an outlet for the external preparation. The outlet tip may be sealed so that it can be easily destroyed during use. Since the outlet is the only place where it comes into contact with the outside air when the lid is removed, it is preferable that the aperture is small in order to suppress the volatilization of the solvent as much as possible. Therefore, the diameter of the outlet is preferably 0.3 to 3 mm, and more preferably 0.5 to 1.5 mm. Moreover, you may make it seal the bottom part (opposite side of an outlet) of a tube container main body, after filling a salicylic acid containing external preparation. As a material of the tube container, any of a metal such as aluminum or a resin such as polyethylene, polypropylene, and polyethylene terephthalate can be used. In the case of a metal tube container, in order to prevent the inner surface of the container from being altered, or to prevent dissolution or alteration of the inner surface of the container by components of the external agent, for example, an organic solvent It is preferable to coat with a resin such as polyethylene, polyethylene terephthalate, polyacrylonitrile, or epoxy resin, and it is particularly preferable to coat with an epoxy resin. The tube container is made of a material having flexibility (bending deformability and shape retention) and required elasticity so that the salicylic acid-containing external preparation filled in the tube container can be pushed out by hand. It is preferable. The tube container made of metal such as aluminum retains its shape when the tube is deformed in order to extrude the salicylic acid-containing external preparation by hand, and there is almost no air in the tube container. Are better. The most preferable tube container is a tube container made of aluminum and having a diameter of an outlet of 0.3 to 3 mm. Among them, an aluminum tube container in which an inner surface is further coated with an epoxy resin. The size (filling amount) of the tube container is not particularly limited, but is usually in the range of 1 to 15 g, and in many cases 2 to 10 g.

  The tip of the outlet of the tube container (opposite the bottom of the tube container main body) is covered with a lid (usually, the lid and the outlet are screwed) to obtain a salicylic acid-containing preparation. The lid can be of any material or shape that is normally used as a lid covering the outlet end of the tube container, and is not particularly limited, but salicylic acid-containing external preparations, especially ether and ethanol as organic solvents. In order not to be affected by the above, it is preferable to use a polyolefin such as polyethylene or polypropylene, and it can be produced by a normal molding method such as injection molding.

2. Characteristics of the salicylic acid-containing preparation The salicylic acid-containing preparation of the present invention is a salicylic acid-containing external preparation when the salicylic acid-containing preparation is used because the salicylic acid-containing external preparation of a specific composition is a salicylic acid-containing preparation filled in a tube container. Volatilization of ether and ethanol, which are organic solvents, can be prevented for a long time. As a result, the composition of the salicylic acid-containing external preparation can be maintained constant, and the therapeutic effect of the disease can be stably exhibited for a long period of time.

  In addition, the salicylic acid-containing preparation of the present invention is a composition of the salicylic acid-containing external preparation because the salicylic acid-containing external preparation filled in the tube container does not cause dripping or poor liquid drainage and is excellent in quick drying. Since it can be applied to the diseased part in a state where is kept constant, the therapeutic effect of the disease can be exhibited stably for a long period of time.

(Liquid dripping)
The dripping of the salicylic acid-containing external preparation in the salicylic acid-containing preparation can be evaluated and determined by the following method. That is, the salicylic acid-containing preparation in which the external preparation containing salicylic acid is filled in the tube container is removed with the lid removed, the tube container outlet is turned downward, and the tip of the tube container outlet is placed on the desired horizontal base. The tube container is supported by a desired jig so that the inverted state can be maintained at a distance of 5 cm. The tube container in an inverted state is allowed to stand for 1 minute in an atmosphere of a temperature of 23 ° C. and 50% RH, and the presence or absence of leakage of the salicylic acid-containing external preparation from the outlet is visually observed. If the salicylic acid-containing external preparation does not leak from the outlet until 1 minute has passed since the inverted state, it is determined that “no dripping”. The case where leakage of the salicylic acid-containing external preparation from the outlet is observed is determined as “Liquid dripping”, and the case where it leaks and falls as a droplet is determined as “Significant liquid dripping”. By determining that the salicylic acid-containing external preparation is “no dripping”, the salicylic acid-containing external preparation can be uniformly applied to the diseased area. If the salicylic acid-containing external preparation is judged to be “with dripping” or “with drastic dripping”, the concentration of piroxylin is too low to form a film, making it difficult to apply to the affected area. The salicylic acid-containing external preparation may be applied to normal skin other than the affected area.

[Out of liquid]
The liquid running out of the salicylic acid-containing external preparation in the salicylic acid-containing preparation can be evaluated and determined by the following method. That is, a salicylic acid-containing preparation filled with a salicylic acid-containing external preparation in a tube container is inverted with the outlet of the tube container facing down with the lid attached, and the tube is maintained with a desired jig so that the inverted state can be maintained. Support the container. A tube container supported in an inverted state and a separately prepared glass plate are allowed to stand for 30 minutes in an atmosphere at a temperature of 23 ° C. and 50% RH. Next, the lid is removed from the outlet of the tube container, and the tip of the outlet is immediately brought into contact with a glass plate placed on a horizontal base, and the tube container is linearly moved at a speed of 1 cm / second for 5 seconds (about 5 cm). ) Move on the glass plate, draw a straight line, and lift the tube container vertically. At this time, when the salicylic acid-containing external preparation remains only on the glass side and the liquid breakage between the glass and the tube container is good, it is determined that “the liquid breakage is good”. When the salicylic acid-containing external preparation is in a state of pulling the thread between the glass side and the tube container, it is determined that “liquid breakage is bad”, and when the state of pulling the thread is remarkable, “liquid breakage is extremely bad” judge. When the salicylic acid-containing external preparation is determined to be “good liquid drainage”, the salicylic acid-containing external preparation can be uniformly applied to the affected area of the disease. When the salicylic acid-containing external preparation is determined to be “poor liquid drainage” or “extremely poor liquid drainage”, the salicylic acid-containing external preparation cannot be applied to the diseased part in a predetermined amount, or in some cases, It may be necessary to apply an excessive squeezing pressure in order to apply a predetermined amount of the salicylic acid-containing external preparation to the affected area.

[Quick drying]
The quick-drying property of the salicylic acid-containing external preparation in the salicylic acid-containing preparation can be evaluated and determined by the following method. That is, the normal usage amount (about 0.015 g) of the salicylic acid-containing external preparation is approximately parallel from the outlet of the tube container on a polyester film placed on a horizontal table in an atmosphere of a temperature of 23 ° C. and 50% RH. Apply 5 points at regular intervals. Cover each piece of salicylic acid-containing external preparation that has been applied in a straight line every 1 minute. Cover it with high-quality paper from the top and press it with your fingers to sandwich the salicylic acid-containing external preparation (hereinafter referred to as “crimping operation”). ”Sometimes.) This crimping operation is sequentially performed at the five locations where the salicylic acid-containing external preparation is applied. Next, the high-quality paper covering the salicylic acid-containing external preparation is peeled off, and it is confirmed whether or not the salicylic acid-containing external preparation film is completely formed. Of the places where it was confirmed that the salicylic acid-containing external preparation film was formed, the elapsed time of the place where the elapsed time until the crimping operation was the shortest was measured, and “drying time of the external preparation” (unit: minutes) (The average value of n = 3 is obtained.) If the drying time of the external preparation is within 2 minutes, it can be said that the salicylic acid-containing external preparation is excellent in quick-drying, and a uniform film of the salicylic acid-containing external preparation is formed in a short time after applying a predetermined amount to the diseased part. Therefore, it is preferable. It is particularly preferable that the drying time of the external preparation is 1 minute since a uniform film of the salicylic acid-containing external preparation is formed in the diseased area in less than 1 minute after applying the salicylic acid-containing external preparation. On the other hand, when the drying time of the external preparation is 4 minutes or longer, the salicylic acid-containing external preparation is inferior in quick-drying property, and after applying a predetermined amount of the salicylic acid-containing external preparation to the diseased part, a uniform film of the external preparation is formed. It is necessary to expose the diseased part for a long time until it is unsatisfactory.

[Usage of salicylic acid-containing preparation]
The salicylic acid-containing preparation of the present invention does not require a separate application bar, and can be used by directly applying the salicylic acid-containing external preparation to the affected area from the distal end of the outlet, so that it has excellent applicability. In addition, since the volume of the air present in the tube container is extremely small, the volatilization of the organic solvent in the salicylic acid-containing external preparation is suppressed as much as possible by quickly closing the outlet cover after use, and the content contains salicylic acid. Since the preparation can be used up to the end without solidifying, it has excellent storage stability. Furthermore, for example, a salicylic acid-containing external preparation for normal skin can be obtained by affixing a ring-shaped patch using urethane foam or the like to the skin around the affected area so that the affected area is located in the space in the center of the ring. It can also be used to prevent adhesion.

III. Production method of salicylic acid-containing preparation The production method of the salicylic acid-containing preparation of the present invention is not particularly limited as long as the salicylic acid-containing external preparation having a specific composition can be filled in a tube container, and a normal ointment or other semisolid Can be produced by a method for producing an external preparation and a method for producing an external preparation prepared by filling a tube container with an ointment or other semisolid external preparation. According to the present invention, the following steps (a) to (c):
(A) a step of producing a salicylic acid-containing external preparation at a temperature of 5 to 35 ° C;
(B) a step of filling a tube container with a salicylic acid-containing external preparation in an atmosphere at a temperature of 30 ° C. or lower; and (c) a step of sealing the tube container;
The composition of the salicylic acid-containing preparation for preparation containing the salicylic acid is not changed during the production of the salicylic acid-containing preparation, and the salicylic acid-containing preparation is not altered during the production. A salicylic acid-containing preparation can be obtained, which is preferable.

[Step (a)]
Step (a) is a step of producing a salicylic acid-containing external preparation at a temperature of 5 to 35 ° C. That is, salicylic acid, piroxylin, ether and ethanol, and other components optionally contained (hereinafter, these may be collectively referred to as “components for external use”) are stirred to obtain a salicylic acid-containing topical product having a uniform composition. This is a step of obtaining an agent. The order of blending the components of the external preparation can be determined as appropriate, but first, piroxylin, ether and ethanol are mixed to obtain a uniform composition of piroxylin solution (ie, collodion), and then salicylic acid and other optionally contained By adding this component, a salicylic acid-containing external preparation can be obtained in a short time. In the step (a), heating or cooling may be performed as necessary. However, in the method for producing a salicylic acid-containing preparation of the present invention, the temperature is 5 to 35 ° C., preferably 10 to 32 ° C., more preferably 15 It is characterized in that the temperature is adjusted so as to be within a range of ˜30 ° C. Since the salicylic acid-containing external preparation of the present invention has a specific composition, it is mixed and stirred within a temperature range of 5 to 35 ° C. for a desired time, that is, usually 1 to 120 minutes, preferably 10 to 60 minutes. Thus, a salicylic acid-containing external preparation having a uniform composition can be obtained. Therefore, when manufacturing a salicylic acid-containing external preparation, it is not necessary to perform operations such as heat dissolution and melt stirring, which are usually performed. As a result, in the step of producing the salicylic acid-containing external preparation, the volatilization of the organic solvent is extremely small, and the composition of the resulting salicylic acid-containing external preparation can be made uniform. When the temperature at which the step (a) is carried out is less than 5 ° C., it takes a long time to stir the components of the external preparation and obtain a salicylic acid-containing external preparation having a uniform composition. The composition of the agent may not be uniform. If the temperature at which the step (a) is carried out exceeds 35 ° C., the organic solvent may be volatilized or the composition of the obtained salicylic acid-containing external preparation may not be uniform.

[Step (b)]
Next, the step (b) to be carried out is a step of filling the tube container with the salicylic acid-containing external preparation in an atmosphere at a temperature of 30 ° C. or lower. That is, the salicylic acid-containing external preparation obtained in the step (a) is filled by a generally employed method for filling a tube container. Specifically, the tube container with the outlet tip end closed and the tube body rear end (opposite the outlet) open is inverted and held (the tube body rear end upward). It is possible to employ a method in which a predetermined amount of a salicylic acid-containing external preparation is injected into a tube container. The step (b) is characterized in that the salicylic acid-containing external preparation is filled in an atmosphere at a temperature of 30 ° C. or lower, preferably 10 to 29 ° C., more preferably 15 to 28 ° C. Since the salicylic acid-containing external preparation of the present invention has a specific composition, it can be filled into a tube container in an atmosphere at a temperature of 30 ° C. or lower. Therefore, it is usually carried out when producing a salicylic acid-containing preparation. There is no need to perform operations such as heat-dissolution and heat-softening of salicylic acid-containing external preparations that may occur. As a result, in the step of producing the salicylic acid-containing preparation, the volatilization of the organic solvent is extremely small, and the composition of the salicylic acid-containing external preparation filled in the obtained salicylic acid-containing preparation can be made uniform. When step (b) is carried out in an atmosphere where the temperature exceeds 30 ° C., volatilization of the organic solvent may occur, or the composition of the salicylic acid-containing external preparation filled in the resulting salicylic acid-containing preparation may not be uniform. is there.

[Step (c)]
Then, the process of sealing a tube container is performed as a process (c). Specifically, 1) a method of hermetically sealing the rear end of the tube main body of a tube container into which a predetermined amount of a salicylic acid-containing external preparation has been injected, using a normal hip folding machine, or 2) A method can be employed in which a lid is attached to the distal end portion of the outlet of the tube container into which a predetermined amount of the salicylic acid-containing external preparation has been injected, and sealed by a method such as screwing. Step (c) may be carried out at room temperature, but may be carried out in an atmosphere having a temperature in the range of 5 to 35 ° C., preferably 10 to 32 ° C., more preferably 15 to 30 ° C., for example. By the step (c), a salicylic acid-containing preparation in which the tube container is filled with the salicylic acid-containing external preparation of the present invention can be obtained.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples and comparative examples, but the present invention is not limited to these examples.

[Example 1]
The salicylic acid-containing external preparation having the composition shown in Table 1 was produced at a temperature of 25 ° C. [Step (a)]. Specifically, a predetermined amount of salicylic acid was added to collodion manufactured by Showa Ether Co., Ltd., and stirred and mixed at a temperature of 25 ° C. (30 minutes) to prepare a salicylic acid-containing external preparation. The salicylic acid-containing external preparation is 15% by mass of salicylic acid and 9.1% by mass of pyroxylin, and the remainder is composed of diethyl ether and ethanol [diethyl ether / ethanol (mass ratio) = 2.5 / 1]. It was.

  Next, prepared as described above at the open rear end of a tube container with a screw cap (for filling 3 g) made of aluminum (thickness: about 100 μm) whose inner surface is coated with epoxy resin and having a diameter of 1.0 mm at the outlet. 3 g of the obtained salicylic acid-containing external preparation was injected and filled in an atmosphere at a temperature of 25 ° C. [step (b)]. Subsequently, the rear end of the tube container was sealed with a crease [step (c)] to obtain a salicylic acid-containing preparation.

  About the obtained salicylic acid-containing preparation, the results of the evaluation of dripping, running out of liquid and quick-drying, the concentration of salicylic acid in salicylic acid-containing external preparation (unit: mass%), the concentration of pyroxylin (unit: mass%), And ratio of diethyl ether and ethanol [mass ratio. Hereinafter, it may be referred to as “ether / ethanol (mass ratio)”. And in Table 1. The method for evaluating and evaluating the dripping, running out of liquid and quick drying was the method described above. In Table 1, “No dripping” or “Liquid draining is good” is indicated by “◯”, and “Liquid dripping” or “Liquid dripping is bad” is indicated by “△”. In the case where “there is significant dripping” or “the liquid is drastically bad”, it is indicated by “x”. The quick drying property indicates the “drying time of the external preparation” described above (unit: minutes). When the obtained salicylic acid-containing preparation was used and applied to the skin, the solvent was quickly volatilized and there was no stickiness. Furthermore, when the prepared salicylic acid-containing preparation was used and applied sequentially to five locations on the skin, it was confirmed that uniform films were formed respectively.

[Examples 2 to 5]
A salicylic acid-containing external preparation was prepared in the same manner as in Example 1 except that the composition of the salicylic acid-containing external preparation was changed as shown in Table 1, and then the salicylic acid-containing external preparation was prepared in the same manner as in Example 1. A formulation was obtained. About the obtained salicylic acid-containing preparation, the results of the evaluation of dripping, running out of liquid and quick-drying properties are shown in Table 1 together with the salicylic acid concentration, piroxylin concentration, and ether / ethanol (mass ratio) in the salicylic acid-containing external preparation. Shown in

  When the obtained salicylic acid-containing preparations of Examples 2 to 5 were used and applied to the skin, the solvent was volatilized quickly and there was no stickiness. Furthermore, when the salicylic acid-containing preparations prepared in Examples 2 to 5 were used and applied sequentially to the skin, it was confirmed that a uniform film was formed. In addition, although the salicylic acid containing preparation prepared in Example 4 did not sag, it was confirmed that the salicylic acid containing external preparation swelled in the form of droplets at the outlet of the tube container. Further, in the salicylic acid-containing preparation prepared in Example 5, after applying the salicylic acid-containing external preparation to the skin, some stringing was observed when the tube was separated from the application site.

[Comparative Examples 1 and 2]
A salicylic acid-containing external preparation was prepared in the same manner as in Example 1 except that the composition of the salicylic acid-containing external preparation was changed as shown in Table 1, and then the salicylic acid-containing external preparation was prepared in the same manner as in Example 1. A formulation was obtained. About the obtained salicylic acid-containing preparation, the results of the evaluation of dripping, running out of liquid and quick-drying properties are shown in Table 1 together with the salicylic acid concentration, piroxylin concentration, and ether / ethanol (mass ratio) in the salicylic acid-containing external preparation. Shown in

  From Table 1, the salicylic acid-containing preparations of Examples 1 to 5 in which a tube container was filled with a salicylic acid-containing external preparation containing 10 to 20% by mass of salicylic acid, 8.25 to 9.4% by mass of piroxylin, and ether and ethanol. Has no dripping of the salicylic acid-containing external preparation, has good liquid drainage, has excellent coating properties, and is quick-drying that can quickly form a uniform film by evaporating the solvent quickly. I understood that. In particular, it was found that the salicylic acid-containing preparations of Examples 1 to 3 having an ether / ethanol (mass ratio) of 1: 1 to 4: 1 are particularly excellent in performance regarding liquid dripping and liquid breakage.

  On the other hand, the salicylic acid-containing preparation in which the salicylic acid-containing external preparation of Comparative Example 1 having a concentration of 10% by mass as piroxylin is filled in the tube container has poor liquidity of the salicylic acid-containing external preparation and has good coating properties. It was found that the salicylic acid-containing preparation in which the salicylic acid-containing external preparation of Comparative Example 2 having a low concentration of piroxylin as low as 7.7% by mass was filled in a tube container was salicylic acid. It was found that there was a sag of the contained external preparation, and the applicability was not good.

  The present invention provides a salicylic acid-containing preparation in which a tube container is filled with a salicylic acid-containing external preparation containing 10 to 20% by mass of salicylic acid, 8.25 to 9.4% by mass of pyroxylin, and ether and ethanol. Since a preparation of a salicylic acid-containing external preparation having high dryness and excellent coating properties and storage stability can be provided, the industrial applicability is high.

Moreover, according to the present invention, the following steps (a) to (c):
(A) a step of producing a salicylic acid-containing external preparation at a temperature of 5 to 35 ° C;
(B) a step of filling a tube container with a salicylic acid-containing external preparation in an atmosphere at a temperature of 30 ° C. or lower; and (c) a step of sealing the tube container;
The salicylic acid-containing preparation for preparation can be easily provided with a salicylic acid-containing preparation for external use that has high quick-drying properties and excellent coating properties and storage stability. high.

Claims (6)

  A salicylic acid-containing preparation in which a tube container is filled with a salicylic acid-containing external preparation containing 10 to 20% by mass of salicylic acid, 8.25 to 9.4% by mass of pyroxylin, and ether and ethanol.   The salicylic acid-containing preparation according to claim 1, wherein a ratio (mass ratio) of ether to ethanol is 1: 1 to 4: 1.   The salicylic acid-containing preparation according to claim 1 or 2, which does not contain acetone.   The salicylic acid-containing preparation according to any one of claims 1 to 3, which does not contain any thickener, gelling agent or filler.   The salicylic acid-containing preparation according to any one of claims 1 to 4, wherein the tube container is made of aluminum and the diameter of the outlet is 0.3 to 3 mm. The following steps (a) to (c):
(A) a step of producing a salicylic acid-containing external preparation at a temperature of 5 to 35 ° C;
(B) a step of filling a tube container with a salicylic acid-containing external preparation in an atmosphere at a temperature of 30 ° C. or lower; and (c) a step of sealing the tube container;
The manufacturing method of the salicylic acid containing formulation of any one of Claims 1 thru | or 5 containing this.