JP6967482B2 - Formulation for skin application - Google Patents

Description

The present invention relates to a skin-applied formulation filled in a roll-on container.

Roll-on containers with sponge-made application parts and rotating balls have been developed and used as containers that allow pharmaceuticals and cosmetics to be applied directly to the skin without picking them up with hands or fingers. Among them, the roll-on container has the advantage that physical stimulation is applied by pressing the affected area with the spherical coating part, blood circulation is promoted, and the user can feel like a massage. (Patent Documents 1 to 7) have been reported in which a liquid agent containing the above is filled in a roll-on container. However, the contents of these formulations are liquid, and when used, the contents are discharged from the container due to gravity, causing dripping, and to prevent dripping, it is difficult to discharge the contents, which makes it difficult to apply a blank coat. There was a problem that coating unevenness occurred. In order to solve this, it has been reported that a structure for preventing dripping and empty coating is provided (Patent Documents 6 and 7), and the contact angle and wettability of the liquid with a metal-coated ball material are controlled (Patent Document 2). ).

Japanese Unexamined Patent Publication No. 2013-215448 Japanese Unexamined Patent Publication No. 2013-63961 Japanese Unexamined Patent Publication No. 2014-34572 Japanese Unexamined Patent Publication No. 2014-210716 Japanese Unexamined Patent Publication No. 2014-129295 Japanese Unexamined Patent Publication No. 2005-186997 Japanese Unexamined Patent Publication No. 2013-75710

However, all of these findings are based on liquids with good fluidity, and there are no findings on viscous cream-like or gel-like contents that are not easily discharged from the container due to gravity. When the present inventor filled a roll-on container with a viscous cream or gel-like composition into a roll-on container used in existing pharmaceutical products and examined direct application to the skin, it was not possible to uniformly apply the contents. could not.
Therefore, an object of the present invention is to provide a skin-applying preparation filled in a roll-on container capable of directly applying a cream-like or gel-like content uniformly and while giving an appropriate stimulus.

Therefore, the present inventor has excellent points such as excellent usability, relatively low irritation to the skin and mucous membranes as compared with the liquid preparation, and good percutaneous absorption of the components contained in the contents on the skin. As a result of investigating a preparation in which a cream-like or gel-like highly viscous composition known as described above is filled in a roll-on container and the contents can be uniformly and easily applied onto the skin, the contents The present invention has been completed by finding that the above-mentioned problems can be solved by setting the viscosity of the above to a certain range and setting the two factors of the strength of the container body and its shape restoration property to a certain range.

That is, the present invention provides the following inventions [1] to [3].

[1] A composition for which the viscosity at 25 ° C. is adjusted to 1,000 to 200,000 mPa · s is a preparation for skin application filled in a tubular roll-on container in which a rotating ball is arranged at the mouth of the container. Put 80% of the contents of the container in the container and close it so that the contents do not leak. When a 5 mm cylindrical probe is reciprocated at a constant speed to a certain distance, the pressing strength κ (N / mm ³ ) obtained by the following equation (1) is 0.01 <κ <1 and the following equation (1). A preparation for skin application, wherein the shape restoration rate R (%) obtained in 2) is 15 <R.
F ₁ = κL ... (1)
(F ₁ is the stress during the pressing operation (N / mm ² ), L is the compression distance (mm), and the slope of the straight line region when the compression curve M is drawn is the pressing strength κ (N / mm ³ ). .)

(F ₁ is the stress during the pressing operation (N / mm ² ), F ₂ is the stress during the shape restoration operation (N / mm ² ), L is the compression distance (mm), and the shape with respect to the total stress during the pressing operation. The ratio of the total stress during the restoration operation is defined as the shape restoration rate R (%).)
[2] The formulation according to [1], wherein 1 to 7 rotating balls are arranged.
[3] The preparation according to [1] or [2], wherein the composition has a viscosity at 25 ° C. of 4,000 to 180,000 mPa · s.

By using the skin-applying preparation of the present invention, a cream-like or gel-like drug or cosmetic can be uniformly and easily applied to a desired portion on the skin. In addition, since the container is applied with a certain pressure at the time of application, a skin massage effect can be obtained.

An example of the compression curve M when 1 <κ is shown. An example of the compression curve M in the case of 0.01 <κ <1 and R <15 is shown. An example of the compression curve M when 0.01 <κ <1, 15 <R is shown. It is a figure which shows one form of the roll-on container of this invention.

The content of the preparation for skin application of the present invention is a cream or gel which is a semi-solid preparation having a viscosity different from that of a liquid having good fluidity. Creams and gels are usually produced by adding a viscous agent such as a water-soluble polymer compound to a base such as water to thicken the mixture so as to have a predetermined viscosity. The viscosity is 1,000 to 200,000 mPa · s at a shear rate of 1.0 (1 / s) at 25 ° C. from the viewpoint of no dripping and good coatability. preferable. Compositions with a viscosity of less than 1,000 mPa · s are fluid and easily drip by pressing the roll-on container, and when the viscosity exceeds 200,000 mPa · s, dischargeability from the roll-on container Is significantly reduced. It is more preferably 4,000 to 180,000 mPa · s, further preferably 6,000 to 160,000 mPa · s, and particularly preferably 6,500 to 155,000 mPa · s. Here, the viscosity can be measured using a Brookfield viscometer cone plate type.

Examples of the composition having such a viscosity include an emulsified composition and a gel-like composition. The emulsified composition includes both an oil-in-water emulsified composition and a water-in-oil emulsified composition.

As the composition, both pharmaceuticals and cosmetics can be mentioned, but it is more preferable to apply the composition to pharmaceuticals. As the pharmaceutical product, an emulsified composition or a gel-like composition containing an anti-inflammatory analgesic, a moisturizer, a blood circulation promoter and the like is preferable. In addition to the active ingredient, the composition may contain additives commonly used in pharmaceutical products. As an example, an aqueous base, an oily base, a surfactant, a viscous agent, a preservative, a pH adjuster, a fragrance and the like can be contained.

Examples of the aqueous base include water, polyhydric alcohols, lower alcohols and the like. Examples of the polyhydric alcohol include glycerin, ethylene glycol, propylene glycol and 1,3-butylene glycol. Examples of the lower alcohol include ethanol and isopropanol. These can be used alone or in combination.

Examples of the oily base include ester oils, hydrocarbon oils, silicone oils, higher alcohols, triglycerides and the like. Examples of the ester oil include isopropyl myristate, isopropyl palmitate, cetyl palmitate, ethyl oleate and the like. Examples of the hydrocarbon oil include squalane, white petrolatum, liquid paraffin, gel hydrocarbon and the like. Examples of the higher alcohol include cetanol, behenyl alcohol, stearyl alcohol and the like. Examples of the triglyceride include glycerin trihexaneate, glycerin trioctanoate, glycerin triisooctanoate, glycerin tridecanoate, glycerin tridodecanoate and tri (capril capric acid) glyceryl. These components can also be used alone or in combination.

Examples of the surfactant include a cationic surfactant, an anionic surfactant, an amphoteric surfactant, and a nonionic surfactant, and in particular, an anionic surfactant or a nonionic surfactant. preferable. Examples of the anionic surfactant include sodium lauryl sulfate, hydrotriethanolammonium laurate, sodium polyoxyethylene lauryl ether phosphate, sodium polyoxyethylene cetyl ether phosphate and the like, and nonionic surfactants. Examples thereof include monofatty acid glycerin, polyoxyethylene monofatty acid glycerin, monofatty acid polyethylene glycol, difatty acid polyethylene glycol, sorbitan fatty acid ester, sucrose fatty acid ester, polyoxyethylene alkyl ether and the like, and these may be used alone or in combination. Can be used.

Examples of the viscous agent include polysaccharides, water-soluble polymers and the like. Examples of the polysaccharide include xanthan gum, carrageenan, pectin and the like. Examples of the water-soluble polymer include hypromellose (hydroxypropylmethylcellulose), hydroxypropylcellulose, polyethylene glycol, carboxyvinyl polymer and the like. These components can also be used alone or in combination.

The container filled with the composition is a roll-on container including a container mouth portion and a container body portion. Here, the portion that holds the rotating ball and has the strength to move the ball is referred to as a container mouth portion, and the other portion is referred to as a container body portion. The material of the container mouth portion and the container body portion may be the same or different materials.

The container is a roll-on container in which one or a plurality of rotating balls are arranged at the mouth of the container, and the contents are distributed on the surface of the rotating balls and applied to a desired portion. The ball may be made of metal or resin. The number of balls may be 1 to a plurality, preferably 1 to 7, and more preferably 2 to 5 from the viewpoint of obtaining a massage effect.

The container body is preferably tubular so that the highly viscous contents can be applied via a rotating ball by pressing. The material of the container body is preferably a single-layer or multi-layer tube mainly made of plastic and / or rubber in order to ensure flexibility and shape restoration. Specifically, a single-layer and multilayer tube composed of a single composition such as polyethylene, polypropylene, and polystyrene, or a plurality of compositions in which these are combined, a resin such as polyethylene, polypropylene, and polystyrene, an ethylene vinyl alcohol copolymer, and nylon. Examples thereof include a multi-layer tube having a multi-layer structure by stacking a resin having barrier performance such as, and a laminated tube in which a metal film such as aluminum foil is laminated on a resin such as polyethylene, polypropylene, and polystyrene.

Two factors, the strength of the container body and its shape restoration, are important in that the contents are uniformly and easily applied to the desired site. Put 80% of the contents of the container and close it so that the contents do not leak. When the probe is reciprocated at a constant speed to a certain distance, the pressing force κ (N / mm ³ ) obtained by the following formula (1) is 0.01 <κ <1 and is obtained by the following formula (2). The shape restoration rate R (%) is 15 <R.
F ₁ = κL ... (1)
(F ₁ is the stress during the pressing operation (N / mm ² ), L is the compression distance (mm), and the slope of the straight line region when the compression curve M is drawn is the pressing strength κ (N / mm ³ ). .)

(F ₁ is the stress during the pressing operation (N / mm ² ), F ₂ is the stress during the shape restoration operation (N / mm ² ), L is the compression distance (mm), and the shape with respect to the total stress during the pressing operation. The ratio of the total stress during the restoration operation is defined as the shape restoration rate R (%).)

Here, the compression tester is a device that can apply a load by compressing the test piece and measure the stress applied to the test piece under the compressive load, and is a device that manually compresses or automatically compresses. There is. Specifically, a device generally called a compression tester or a universal tester can be used.

As for the test conditions of the compression test, the reciprocating speed of the cylindrical probe is preferably 10 mm / min , and the distance is preferably 10 mm. The pressing strength κ (N / mm ³ ) is preferably 0.02 to 1.0, more preferably 0.02 to 0.8, and even more preferably 0.02 to 0.5. The shape restoration rate R (%) is preferably 15 to 90%, more preferably 20 to 90%, and even more preferably 20 to 80%.
When the pressing strength and the shape restoration rate are within the above ranges, the container body can be appropriately pressed to apply the contents, and the pressed container returns to the original shape after use. The viscous content can be easily and uniformly applied directly to the desired site on the skin repeatedly and with appropriate irritation from the roll-on container.

The shape of the container body for obtaining the above-mentioned pressing strength and shape restoration rate is not particularly limited, but consideration is given to ease of application to a desired site on the skin, ease of holding and squeezing that affect the massage effect. Then, the content, size and its balance must be set appropriately.

Specifically, a tube having an internal volume of 2 mL to 300 mL is preferable, a tube having a content of 5 mL to 200 mL is more preferable, and a tube having a content of 20 to 150 mL is further preferable. The diameter thereof is preferably 10 to 100 mm, more preferably 20 to 80 mm, and even more preferably 20 to 60 mm.

The diameter of the container mouth is generally determined by the size of the container body, but it can hold a rotating ball and can be freely set so that the ball can move. The gap between the ball and the ball receiving portion at the container mouth may be set in consideration of the holding property of the ball, the mobility of the ball, and the viscosity of the contents passing through the gap, but when applied to the skin, it may be set. , 0.01-200 μm is preferable.

Next, the present invention will be described in more detail with reference to examples.

Test Example 1: Strength of container body and its shape resilience and coatability Example 1 to Example 6, Comparative Example 1 to Comparative Example 3
The emulsified compositions of the formulations shown in Table 1 below were filled in various containers in an amount of 80% (48-80 g) based on the total volume (60-100 mL) of the container.

Close the container so that the contents do not leak, and use a compression tester to place a cylindrical probe with a diameter of 5 mm at a constant speed of 10 mm / min from the container mouth to the center of 1/3 of the total length of the container body. It was reciprocated to 10 mm. The pressing strength κ (N / m ³ ) and the shape restoration rate R (%) at this time were determined.
F ₁ = κL ・ ・ ・ (1)
(F ₁ is the stress during the pressing operation (N / mm ² ), L is the compression distance (mm), and the slope of the straight line region when the compression curve M is drawn is the pressing strength κ (N / mm ³ ). .)

(F ₁ is the stress during the pressing operation (N / mm ² ), F ₂ is the stress during the shape restoration operation (N / mm ² ), L is the compression distance (mm), and the shape with respect to the total stress during the pressing operation. The ratio of the total stress during the restoration operation is defined as the shape restoration rate R (%).)
The results are shown in Table 2. Note that FIG. 1 shows a compression curve M when 1 <κ, and FIG. 2 shows a compression curve M when 0.01 <κ <1, but R <15. FIG. 3 shows the compression curve M when 0.01 <κ <1, 15 <R.
Table 2 also shows the results of evaluation of the ease of application when the container was repeatedly squeezed by five panelists.
◯: All panelists evaluated that it was easy to grip and apply.
Δ: Three panelists evaluated that it was easy to grip and easy to apply.
X: All panelists evaluated that it was difficult to grip and apply.

Test Example 2: Viscosity and coatability of the contents Examples 7 to 13 and Comparative Examples 4 to 5
The roll-on container (content volume 100 mL) of Example 1 was filled with 80 g of various commercially available cream-like or gel-like pharmaceutical compositions A to I having different viscosities, and the ease of application was evaluated. The roll-on container used is shown in FIG. 1, and the evaluation results are shown in Table 3.

Five panelists evaluated the ease of application during the application operation.
◯: All panelists evaluated that it was easy to apply.
Δ: Three panelists evaluated that it was easy to apply.
X: All panelists evaluated that it could not be applied.

Claims (3)

The composition whose viscosity at 25 ° C. was adjusted to 4,000 to 180,000 mPa · s is a skin application product filled in a tubular roll-on container in which a rotating ball is arranged at the container mouth. Put 80% of the contents of the total capacity of the container in the container and close it so that the contents do not leak. When the cylindrical probe is reciprocated at a speed of 10 mm / min to a distance of 10 mm, the pressing strength κ (N / mm ³ ) obtained by the following equation (1) is 0.01 <κ <1 and the following. A product for skin application, wherein the shape restoration rate R (%) obtained by the formula (2) is 15 <R.
F ₁ = κL ・ ・ ・ (1)
(F ₁ is the stress during the pressing operation (N / mm ² ), L is the compression distance (mm), and the slope of the straight line region when the compression curve M is drawn is the pressing strength κ (N / mm ³ ). .)

(F ₁ is the stress during the pressing operation (N / mm ² ), F ₂ is the stress during the shape restoration operation (N / mm ² ), L is the compression distance (mm), and the shape with respect to the total stress during the pressing operation. The ratio of the total stress during the restoration operation is defined as the shape restoration rate R (%).) The product according to claim 1, wherein 1 to 7 rotating balls are arranged. Product according to claim 1 or 2, wherein viscosity of 6,000~160,000 mPa · s at 25 ° C. of the composition.

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