CN113164511A

CN113164511A - Foaming external composition

Info

Publication number: CN113164511A
Application number: CN201980083678.1A
Authority: CN
Inventors: 桑原强志; 加茂骏介
Original assignee: Nitto Kitako Co ltd
Current assignee: Nitto Kitako Co ltd; Nitto Medic Co Ltd
Priority date: 2018-12-19
Filing date: 2019-12-18
Publication date: 2021-07-23
Also published as: JP6781358B1; KR20210106405A; JP2020176148A; KR102584365B1; WO2020130035A1; JPWO2020130035A1

Abstract

The present invention provides an external composition which contains a polymeric surfactant as a foaming component and forms foam when used. The topical compositions of the present application are provided filled, for example, in a pump foamer container or an extruded foamer container.

Description

Foaming external composition

Technical Field

The present invention relates to a composition for external use which forms bubbles at the time of use.

Background

In recent years, aerosol preparations which are ejected in a foam form using a foamable liquid and a propellant have been developed from the viewpoint of excellent usability such as ease of application without sagging and smooth spreading. However, since this aerosol type preparation uses a liquefied gas such as liquefied propane as a propellant, there are problems in terms of environmental aspects such as the control of volatile organic compounds and the inability to reuse used cans, and recently, a non-gaseous type preparation in a bubble form at the time of discharge using a pump foamer container, an extrusion foamer container, or the like has been developed.

In general, a surfactant is known as a component for forming bubbles. Anionic surfactants are considered to have a high foaming power but have irritativeness, and nonionic surfactants are considered to have low irritativeness but have low foaming power, and thus a formulation having satisfactory foaming power and satisfactory safety cannot be obtained by one surfactant. It is reported that safe and good foams can be formed by combining a polyoxyethylene alkyl ether and/or a polyoxyethylene alkenyl ether with a polyoxyethylene fatty acid ester and/or a polyoxyethylene hydrogenated castor oil as a nonionic surfactant (patent document 1).

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open publication No. 2017-214407.

However, in order to further reduce the burden on the skin, it is preferable to use a smaller amount of the additive, and development of a novel foaming external composition which can produce a more favorable foam quality, a moderate foam-sustaining feeling (foam-sustaining feeling) without sagging, and a foam having a favorable feeling in use with a smaller amount of the additive is strongly desired.

Disclosure of Invention

Problems to be solved by the invention

The invention provides a foaming external composition which can generate more favorable foam quality, does not drop, has proper foam lasting feeling and favorable use feeling.

Means for solving the problems

In view of such circumstances, the present inventors have intensively studied to find that: the desired object can be achieved by using a polymeric surfactant as a foaming agent. That is, the present invention relates to an external composition which contains a polymeric surfactant as a foaming component and forms foam at the time of use.

Effects of the invention

As is evident from the results of the examples described below: according to the formulation of the present invention, a novel composition for external use having a better foam quality, a moderate foam-sustaining feeling without sagging, and a good feeling of use can be obtained, and particularly, the composition can be used as a non-gaseous preparation in which a pumping foamer container or an extrusion foamer container requiring no gas is in a bubble form at the time of discharge, and is suitable for the treatment of skin diseases such as atopic dermatitis.

Drawings

FIG. 1 is a photograph showing the result (bubble formation) of example 1.

FIG. 2 is a photograph showing the results of example 2 (persistence of foam (evaluation with polyurethane)).

FIG. 3 is a photograph showing the result of example 2 (persistence of bubbles (evaluated by Kimtosel)).

FIG. 4 is a photograph showing the results (dripping of bubbles) of example 2.

Detailed Description

The composition for external use of the present invention can be used as a spray for forming a bubble of the stock solution and spraying it on the skin at the time of use, or as a base thereof. The stock solution is a foamable liquid composition. The composition for external use of the present invention can be used by using a foam discharging container that sprays the stock solution in the container by a pump without using a propellant. The foam discharge container is not particularly limited as long as it can discharge the composition of the present invention in a foamed state by mixing it with air, and for example, a pump spray (pump foamer) container discharged by an extrusion pump, an extrusion foamer container which extrudes a tube portion of a flexible container, or the like can be suitably used.

The polymer surfactant of the present invention is at least one selected from cellulose derivatives such as ethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose (hypromellose), carboxymethyl cellulose, sodium carboxymethyl cellulose, and carboxymethyl ethyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, and polyacrylic acid. Preferably at least one selected from the group consisting of cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol and polyacrylic acid, more preferably at least one selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol and polyacrylic acid, and particularly preferably hydroxypropylmethylcellulose (hypromellose). As the hypromellose, hypromellose having a substitution degree type of 2906 or 2910 prescribed in japanese pharmacopoeia is suitably used. Can be exemplified by: the high molecular surfactant is contained in an amount of 0.01 to 10 wt%, preferably 0.1 to 5 wt%, more preferably 0.2 to 3 wt%, particularly about 0.5 wt%, about 0.75 wt%, or about 1 wt% based on the total amount of the composition. It is to be noted that, in the present specification and claims, where "about" is mentioned in relation to a numerical value, a value up to ± 20%, or ± 10% or ± 5% of the indicated numerical value is included. According to the present invention, even if only 1 kind of polymeric surfactant is used, a desired effect can be achieved.

The composition of the present invention may further contain, in addition to the above-mentioned polymeric surfactant, other surfactants which can be used in the fields of medicines and cosmetics, such as anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants, as necessary. Examples of the anionic surfactant include: N-acyl-N-methylglycinate, sodium alkylsulfonate, sodium alkylsulfate, polyoxyethylene alkyl ether carboxylate, sodium lauryl sulfate, and the like; as the cationic surfactant, for example, there can be exemplified: benzalkonium chloride, benzethonium chloride, aliphatic amine salts, aliphatic quaternary ammonium salts, and the like; as the amphoteric surfactant, for example, there can be exemplified: lauryl dimethyl glycine betaine, stearyl dimethyl glycine betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryl dimethyl amine oxide, lauramidopropyl betaine, cocamidopropyl betaine, lauryl hydroxysulfobetaine, etc.; as the nonionic surfactant, for example, there can be exemplified: polyoxyethylene alkyl ethers, polyoxyethylene alkenyl ethers, polyoxyethylene hydrogenated castor oils, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid glycerides, polyoxypropylene polyoxyethylene alkyl ethers, polyoxypropylene polyoxyethylene alkenyl ethers, and the like.

Alcohols may be included in the compositions of the present invention. As the alcohol, there can be exemplified: monohydric alcohols such as ethanol and isopropanol; polyhydric alcohols such as polyethylene glycol, glycerol, 1, 3-butanediol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerol, isoprene glycol, 1, 2-pentanediol, 2, 4-hexanediol, 1, 2-hexanediol, and 1, 2-octanediol may include 1 or 2 or more. In particular, examples may be suitable: glycerin, propylene glycol, polyethylene glycol, and 1, 3-butylene glycol. The total content of the alcohol is 5 to 60 wt%, preferably 10 to 50 wt%, and more preferably 15 to 40 wt%.

The composition of the present invention preferably has a pH value in the range of 3 to 12. More preferably, the pH value is 4 to 10. As pH adjusters for adjusting the composition to a pH value within the above range, as pH adjusters used for adjusting to a low pH range, there are exemplified: examples of the pH adjusting agent used for adjusting to a high pH range include potassium dihydrogen phosphate and citric acid: sodium hydroxide, potassium hydroxide, sodium lactate, sodium citrate, L-arginine, diisopropanolamine, and the like. Particularly preferred pH adjusting agents include: potassium dihydrogen phosphate, potassium hydroxide, sodium citrate, citric acid, diisopropanolamine, sodium edetate, etc.

The liquid composition according to the present invention may contain additives commonly used in external preparations for skin, such as a preservative (preservative), an antioxidant, a humectant, a stabilizer, and an ultraviolet absorber, in addition to the above components.

Examples of the preservative include: parabens (Parabens) such as methyl paraben, ethyl paraben and propyl paraben, sodium benzoate, phenoxyethanol and the like. The preservative may be used alone or in combination of two or more. The content of the preservative in the composition is preferably in the range of 0.01 to 1% by weight, and more preferably in the range of 0.1 to 0.5% by weight.

The composition of the present invention may be blended with a pharmaceutically active ingredient or may be provided as a cosmetically active ingredient in the form of a base for use in the manufacture of a pharmaceutical or cosmetic product, and may further comprise a pharmaceutically active ingredient. Compositions comprising pharmaceutically active ingredients are also one of the aspects of the present invention.

The composition of the present invention is suitable as an external preparation to be applied to the skin, and is suitable for skin diseases such as inflammation of the skin, eczema, atopic dermatitis, psoriasis, acne, scar, bedsore, acne, and the like (including curing, symptom improvement, exacerbation prevention, disease prevention, and the like), and is suitable for not only the skin but also hairy parts such as the scalp.

The active ingredient to be incorporated in the composition of the present invention is not particularly limited as long as it is an active ingredient that is applied to the skin and supplied, and examples thereof include: steroids, non-steroidal anti-inflammatory drugs, bactericides, antibacterial agents, antifungal agents, vitamins, immunosuppressants, mucopolysaccharides, cAMP derivatives, fibroblast growth factors, naphthoic acid derivatives, benzoyl peroxide and the like. The steroid is not particularly limited as long as it has a steroid skeleton, and examples thereof include: cortisone, hydrocortisone, fludrocortisone acetate, prednisolone, methylprednisolone, dexamethasone, betamethasone, clobetasol and derivatives thereof; as the above-mentioned non-steroidal anti-inflammatory drugs, there can be exemplified: indomethacin, suprofen, ketotifen, allantoin, dipotassium glycyrrhizinate, etc.; as the above-mentioned bactericide, there can be exemplified: chlorhexidine gluconate, benzalkonium chloride, and the like; as the above antibacterial agent, there may be exemplified: tetracycline hydrochloride, chloramphenicol, neomycin sulfate, nadifloxacin, clindamycin phosphate, ozenoxacin, oxytetracycline hydrochloride, polymyxin B sulfate, gentamicin sulfate, sodium fusidate, and the like; as the antifungal agents, there may be exemplified: terbinafine, butenafine, bifonazole, ketoconazole, and the like; examples of the vitamins include: vitamin a or a derivative thereof (e.g., vitamin a oil), vitamin B or a derivative thereof (e.g., panthenol), vitamin C or a derivative thereof, vitamin D or a derivative thereof (e.g., active vitamin D3), vitamin E or a derivative thereof (e.g., tocopherol acetate), vitamin K or a derivative thereof, and the like; as the above-mentioned immunosuppressant, there can be exemplified: tacrolimus, cyclophosphamide, and the like; examples of the mucopolysaccharides include: heparin analogues or hyaluronic acid and salts thereof; as cAMP derivatives, there may be exemplified: sodium braddigesin, and the like; as the fibroblast growth factor, there can be exemplified: trafosmin, and the like; as naphthoic acid derivatives, there can be exemplified: adapalene, and the like. The content of these is 0.001 to 10% by weight, preferably 0.01 to 10% by weight, and more preferably 0.01 to 5% by weight. In particular, examples may be suitable: a composition for external use containing mucopolysaccharides such as heparin analogues, hyaluronic acid and salts thereof.

In particular, the foamable composition containing heparin analogues is also suitable as a composition for treating dry skin diseases, asteatosis, progressive palmar and palmar keratoderma, chilblain, hypertrophic scars/keloids, pain and inflammatory diseases due to blood circulation disorders (induration and pain after injection), thrombophlebitis (including hemorrhoids), swelling/hematoma/tenosynovitis/myalgia/arthritis after trauma (bump, sprain, contusion), myotorticollis, and the like, because heparin analogues have a blood coagulation inhibitory action, a blood flow increasing action, a hematoma regression promoting action, a horny water retention enhancing action, and a fibroblast proliferation inhibitory action.

The present invention will be described in more detail below with reference to experimental examples to explain the effects of the present invention, but these are merely examples, and the scope of the present invention is not limited to these experimental examples.

Examples

Example 1

The prepared sample was filled in a pump foamer container according to the following formulation, and whether or not foam was formed when discharged from the container was evaluated (table 1, fig. 1).

It should be noted that samples A to I and N are polymeric surfactants.

[ Table 1]

The source of each sample used in this example is as follows.

[ Table 2]

Therefore, the following steps are carried out: the polymeric surfactants incorporated in the foamable external composition of the present invention are each effective as a foaming agent alone.

Example 2

The prepared sample was filled in a pump foamer container according to the following formulation, and the presence or absence of foam formation, foam quality, foam retention time and the presence or absence of dripping were measured (tables 3 and 4). Under condition a, a pad made of a polyurethane material was used as a material close to healthy human skin, and under condition B, kimtopel, which is supposed to be relatively heavy and dry skin, was discharged thereon (fig. 2 and 3). After being discharged onto a pad of polyurethane material, the sheet was tilted at about 45 ℃ to observe whether or not there was any dripping (fig. 4).

[ Table 3]

[ Table 4]

The hypromellose alone formed a good quality and stable foam that remained after 5 minutes, and no dripping was observed after 3 minutes. This effect is further improved by combining polyols. On the other hand, the preparation in which polyoxyethylene cetyl ether or polyoxyethylene lauryl ether is combined with polyoxyethylene hydrogenated castor oil 60 does not form bubbles, or even if bubbles are formed, the elasticity is low and the retention time is short, and even if the polyol is mixed, the elasticity and retention time are inferior to those of the preparation using hypromellose in dropping.

Example 3

The presence or absence of foam formation based on concentration was evaluated using hypromellose of different viscosity. The evaluation criteria for the foam quality were the same as in example 1.

[ Table 5]

Regardless of the viscosity of hypromellose, bubbles form at concentrations above 0.2%.

Example 4

2 compositions containing heparin analogues at a concentration of 0.1 or 0.3% in the formulations shown in the material name 2 of Table 2 of example 2 were prepared and filled in a pump foamer container, and the presence or absence of foam formation, foam retention time and the presence or absence of dripping were measured (Table 5).

[ Table 6]

As shown in table 5, using the composition of the present invention, a heparin analogue-containing pharmaceutical composition having a favorable texture and favorable bubble quality in elasticity and having a moderate foam retention without sagging was obtained.

Claims

1. A composition for external use, which comprises a polymeric surfactant as a foaming component and forms foam upon use.

2. The composition according to claim 1, wherein the polymeric surfactant is at least one selected from the group consisting of cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycol, and polyacrylic acid.

3. The composition according to claim 2, wherein the cellulose derivative is at least one selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose and methylcellulose.

4. The composition of claim 3, wherein the cellulose derivative is hydroxypropyl methylcellulose.

5. The composition of any one of claims 1 to 4, further comprising a polyol.

6. The composition of claim 5, wherein the polyol is 1, 3-butanediol.

7. The composition according to any one of claims 1 to 6, wherein the hydroxypropyl methylcellulose is contained in an amount of 0.2 to 3% by weight and the 1, 3-butanediol is contained in an amount of 15 to 40% by weight, based on the total amount of the composition.

8. A composition as claimed in any one of claims 1 to 7, which comprises at least one pharmaceutically active ingredient.

9. The composition according to claim 8, wherein the pharmaceutically active ingredient is mucopolysaccharide.

10. The composition according to claim 8 or 9, wherein the content of the pharmaceutically active ingredient is 0.01 to 5% by weight relative to the total amount of the composition.

11. The composition according to claim 10, which comprises a heparin analogue and/or hyaluronic acid or a salt thereof as a pharmaceutically active ingredient.

12. A composition formed by filling the composition of any of claims 1-11 in a pump foamer container or an extrusion foamer container.

13. A composition as claimed in any one of claims 1 to 12 for use in the treatment of a skin disorder.