JPS63208518A - Novel tolnaftate-containing gelatinous emulsion - Google Patents

Abstract

PURPOSE:To obtain a stable tolnaftate-containing gelatinous emulsion useful as an antitrichophytial agent for external use, by adding a polyhydric alcohol ester of a fatty acid, oily ingredient, emulsifying agent, water-soluble high polymer and water to tolnaftate and crotamiton and emulsifying the resultant blend. CONSTITUTION:A stabilized tolnaftate-containing gelatinous emulsion, obtained by adding (C) a polyhydric alcohol ester of a fatty acid, e.g. glycerol ester of a fatty acid, propylene glycol ester of a fatty acid or a mixture thereof, (D) an oily ingredient, (F) an emulsifying agent and (F) water to (A) tolnaftate and (B) crotamiton, emulsifying the resultant blend and adding (G) a water-soluble high polymer to the aqueous phase in the process to increase the viscosity of the aqueous phase and useful as an antitrichophytial agent as a quasi-drug for external use without causing deposition of tolnaftate crystals with time and further separation of a base for a long period.

Description

[Detailed description of the invention] 〔Technical field〕 TECHNICAL FIELD The present invention relates to an antiwhitening agent as an external medicine.

More specifically, the present invention relates to a stabilized tolnaftate-containing gel emulsion in which tolnaftate crystals do not precipitate at all. The present invention relates to an anti-white hemorrhoid agent for external use containing a resin and water.

[Prior art]

Tolnaftate (N-methyl-N-(3-tolyl)diocarbamic acid 2-naphthyl ester) is used as an anti-whitening agent for the treatment of leukemia, stubbornness, patchy varicose albinism, and strangles. Currently, it is frequently used in various dosage forms such as liquid, ointment, and powder.

When formulating tolnaftate-containing ointment preparations, tolnaftate itself is almost insoluble in water, poorly soluble in methanol and ethanol, and contains chloroform, acetone,
Because tolnaftate is easily soluble in carbon tetrachloride, it has been difficult to create stable formulations in which tolnaftate crystals do not precipitate over a long period of time using emulsions or gels containing water.

Conventionally known emulsions and gels for topical use of tolnaftate include those that use diethyl sebacate and diethyl phthalate as solubilizing agents for tolnaftate (
(see JP-A No. 54-119023), and those using di-lower alkyl esters of phthalic acid, succinic acid, maleic acid, adipic acid, and sepacic acid (see JP-A-54-119023).
0-33366), those using methyl ethyl ketone (see JP-A-55-45662), and those using propyl carbonate (JP-A-61-187).
(see Publication No. 16) is known.

Although emulsion-type bases generally have better permeability of active ingredients into the skin than ointments and liquids, emulsions have lower base stability than other ointments and liquids. However, it is often seen that the base material separates into an aqueous phase and an oil phase due to the influence of temperature and other factors.

[Disclosure of the invention]

The present inventors have discovered that when tolnaftate is dissolved and emulsified by containing an oily component, an emulsifier, and water, tolnaftate crystals do not precipitate over time.
Furthermore, as a result of intensive research aimed at developing substances to create stable emulsions that do not cause base separation over long periods of time, we found that tolnaftate and crotamiton were combined with polyhydric alcohol fatty acid esters, such as glycerin fatty acid esters, propylene glycol fatty acid esters, and propylene glycol fatty acid esters. , and emulsify the mixture by adding an oily component, an emulsifier, and water.
Furthermore, it has been found that a stable emulsion can be obtained by adding a water-soluble polymer resin to the aqueous phase to increase the viscosity of the aqueous phase. At high temperatures (60°C), some commercially available external emulsions for athlete's foot already show a separation phenomenon after 2 days, while commercially available products with a water-soluble base containing tolnaftate liquefy at 60°C and turn yellow over time. ~There are products that turn brown, and in the case of water-soluble bases, when the base is returned to room temperature and left to stand, a phenomenon of non-uniform agglomeration was observed, but for the tolnaftate-containing gel emulsion according to the present invention, The product was completely stable at 60° C. for a long period of time, with no change in appearance color and no separation of the base. In addition, some commercially available emulsions containing tolnaftate show tolnaftate crystals when observed under a microscope, and even in products where no crystals are observed, crystals precipitate when left at low temperatures (2°C) for 4 days. Although there are products in which this phenomenon is observed, the tolnaftate-containing gel emulsion according to the present invention did not show precipitation of tolnaftate crystals when left at 2° C. for a long period of time.

Crotamiton, or N-ethyl-N-[2-methylphenyl]-2-butynamide, is a colorless to pale yellow oily substance that is easily soluble in water and miscible with ethanol, ether, and benzene. External preparations containing 10% crotamiton are used to treat eczema, measles, neurodermatitis, skin pruritus, and the like.

Therefore, when the crotamiton used in the present invention is used within the range of 10% in the base, it not only acts as a solubilizer for tolnaftate, but also exhibits the unique effects of crotamiton, such as an antipruritic effect.

To illustrate the method for producing the tolnaftate-containing gel emulsion according to the present invention, 1% by weight of tolnaftate is mixed with 5% crotamiton.
~10% by weight and glycerin Qhin4 = m f
-y ;, I+, +: l-re -1'
M L, 'L'/ & I+ -+
ILn is dissolved in 10 to 20% by weight of a fatty acid ester or a mixture thereof, and 10 to 20% of the oily component is dissolved therein.
Add 20% by weight of emulsifier and 5 to IO weight% of emulsifier, then add a water phase component prepared by mixing a solution of 1 to 5% by weight of a water-soluble polymer resin and a water-soluble component in 30 to 60% of purified water. It is manufactured by emulsifying it. Examples of the glycerin fatty acid ester used here include glycerin laurate, glycerin myristate,
Examples include glycerin palmitate, glycerin stearate, and glycerin oleate, and these may be used alone or in a mixture thereof. Specifically, for example, the product name Miglyol (manufactured by Guinamit Nobel Chemicals), 5efso1318,
338, 618, 668 (manufactured by Nikko Chemicals)
. Examples of the propylene glycol fatty acid ester include propylene glycol laurate, propylene glycol myristate, propylene glycol palmitate, propylene glycol stearate, propylene glycol oleate, etc. These may be used alone or in mixtures thereof. used as Specifically, for example, the product name is 5erso.
1 22g, 220 (manufactured by Nikko Chemicals Co., Ltd.), and oily ingredients include beeswax, paraffin wax, stearic acid, stearyl alcohol, cetanol, biphenyl alcohol, isopropyl myristate, liquid paraffin, lanolin, etc. These are used alone or in an appropriate combination of two or more. Furthermore, as an emulsifier, for example, polyoxyethylene fatty acid ester, higher fatty acid glycerin ester, sugar ester, polyoxyethylene sorbitan higher fatty acid ester (trade name: Tween Atlas Co., Ltd.), sorbitan higher fatty acid ester (trade name: Span Atlas Co., Ltd.) These can be used alone or in an appropriate combination of two or more. Examples of water-soluble polymer substances include sodium carboxymethyl cellulose (trade name Hibiswako, manufactured by Wako Pure Chemical Industries, Ltd.), carboquinovinyl polymer (trade name Carbobol, manufactured by Chugai Boeki Co., Ltd.), brown algae extract (trade name For products that require pH adjustment, the pH must be adjusted in advance with an organic or inorganic base substance.
used.

The tolnaftate-containing gel emulsion according to the present invention may optionally contain other drugs, such as local anesthetics, keratin softeners, bactericidal agents, and as stabilizers, preservatives, antioxidants, and preparations of external drugs such as fragrances and pigments. It can contain excipients commonly used in chemical preparations. Examples of the present invention are shown below.

Example l Crotamiton 5% by weight and glycerin fatty acid ester 15
After adding and dissolving 1% by weight of tolnaftate, oil phase components of 5% by weight of stearic acid, 1% by weight of biphenyl alcohol, 1% by weight of Sarashimitsu 0, 8% by weight of isopropyl myristate, and polyoxyethylene. Add emulsifiers of 2% by weight of monostearate and 5% of glyceryl monostearate, and dissolve by heating at 80°C.

Separately, purified water 50.3% by weight, alda colloid 1.5% by weight, propylparaben 0.1% by weight, methylparaben 0
．． 1% by weight was added and dissolved by heating, and the aqueous phase component to which 5% by weight of propylene glycol was added was heated to 85°C, gradually added to the previously prepared oil phase to emulsify, and while cooling with water. After cooling to 25-30° C., the mixture is left to stand to obtain a tolnaftate-containing gel emulsion (wt % is based on the weight of the emulsion obtained).

In Examples 2.3 and 4 shown in the table below, tolnaftate-containing gel emulsions were obtained by following the manufacturing method of Example 1 according to the indicated formulations.

Tolnaftate solubilizer Crotamiton glycerin fatty acid ester propylene glycol fatty acid ester emulsifier Polyoxyethylene monostearate monostearate glycerin oil phase component Biphenyl stearate alcohol salicylic beeswax isopropyl myristate moisturizer Propylene glycol glycol
Serine Water-soluble polymer substance Algecolloid Sodium carboxymethyl cellulose Purification Water preservative Propylparaben Methylparaben

Claims (1)

[Claims] A stabilized tolnaftate-containing gel emulsion obtained by emulsifying tolnaftate and crotamiton, containing a polyhydric alcohol fatty acid ester, an oily component, an emulsifier, a water-soluble polymer substance, and water.