JPS58162516A - Steroid-containing water-in-oil type emulsion - Google Patents

Abstract

PURPOSE:The titled emulsion for remedying skin diseases, having improved thermal stability, and long-term storage with scarcely found reduction in content due to decomposition of main drug, containing polyoxyethylene polyoxypropylenecetyl ether as an emulsifying agent. CONSTITUTION:A water-in-oil type emulsion of steroid-based drug (preferably corticosteroid such as budesonide, betamethasone valerate, etc.) containing polyoxyethylene polyoxypropylenecetyl ether as an emulsifying agent. The emulsion can stand long-term storage at high temperature. White vaseline, liquid paraffin, olive oil, stearic acid, stearyl alcohol, etc. is used as an oily phase component for the emulsion, and a common additive such as an antiseptic, stabilizer, solubilizer, humectant, pH adjustor, etc. may be added to the emulsion.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a water-in-oil emulsion of a steroid drug containing polyoxyethylene polyoxypropylene cetyl ether as an emulsifier. .

Anti-inflammatory nutroids are added to cream or ointment bases as agents for treating skin diseases and are widely applied to skin diseases. Different bases are used depending on the disease state of the skin, but when applying creams to difficult-to-treat skin diseases such as psoriasis, water-in-oil creams are preferred over oil-in-water creams because of the skin-sealing properties of the base. Creams have a higher therapeutic effect;
Therefore, it has been desired to develop a topical steroid preparation formulated as a water-in-oil cream.

However, compared to oil-in-water creams, water-in-oil creams have a continuous phase of oil, so even if a small amount of oil separates, it remains without volatilizing like water, reducing its commercial value. However, it has been difficult to obtain water-in-oil creams that are stable over a wide temperature range because of the limited number of types of emulsifiers that can be used.

As emulsifiers to improve these drawbacks, generally low HLB emulsifiers are used, such as sorbitan fatty acid esters, lanolin derivatives, glycerin fatty acid esters, polyglycerin fatty acid esters, glohylene glycol fatty acid esters, polyoxyethylene alkyl ethers, and polyoxyethylene alkyls. Phenyl ether has been used, and as an emulsification aid, for example, cholesterol, metal soap, or an emulsifying wax containing a mixture of these has been used.

When these emulsifiers and emulsification aids are used, at around room temperature,
Although a stable cream can be obtained, the cream tends to separate under high or low temperature conditions and has a tendency to be inferior in quality to oil-in-water creams.

Additionally, when the drug is a steroid, the stability of the drug itself is often compromised due to interactions with trace metals and emulsifiers, and therefore, compared to oil-in-water creams,
It has been extremely difficult to develop a water-in-oil cream containing steroids that can be put to practical use.

The inventors of this invention have discovered that when polyoxyethylene polyoxypropylene cetyl ether is used as an emulsifier,
It has been found that a water-in-oil emulsion with excellent thermal stability can be obtained, and the steroid drug contained in the emulsion is hardly decomposed.

The water-in-oil emulsion of the steroid drug of the present invention has a composition containing polyoxyethylene polyoxypropylene cetyl ether as an emulsifier.

Corticosteroids are preferred as the herbal medicines used in the emulsion of this invention, and specific examples include betamethacin nivalerate, fluocinonide, budesonide, fluocinolone acetonide, beclomethasone propionate, drocortisone butyrate, triamcinolone acetonide, Examples include diflucortolon valerate, betamethacin dipro←°onate, clobetasol propionate, hydrocortisone, hydrocortisone acetate, fluprednisolone, dexamethacin, and dexamethacin acetate.

? The emulsion of the jD invention has a composition containing an oil phase component and an aqueous phase component in addition to a steroid drug as a main drug and polyoxyethylene polyoxypropylene cetyl ether as an emulsifier.

The oil phase component may be one that is commonly used as an oil phase component of emulsions, and specifically includes fats and oils such as olive oil and corn oil, waxes such as beeswax, carnauba wax, and lanolin, liquid paraffin, and white oil. Hydrocarbons such as vaseline, paraffin, microcrystalline wax, and squalane, higher fatty acids such as stearic acid, palmitic acid, and behenic acid, higher alcohols such as nutaryl alcohol and behenyl alcoholonone, isopropyl myrinutate, and oleyl oleate. Examples include esters.

Further, distilled water is usually used as the aqueous phase component.

The proportion of polyoxyethylene polyoxypropylene cetyl ether added in the emulsion is appropriately determined depending on the types and amounts of the main drug, oil phase component, and aqueous phase component.

In addition to the above-mentioned components, the emulsion of the present invention contains commonly used additives such as preservatives, antioxidants, stabilizers, solubilizers, humectants, and pH adjusters. It's okay.

As is clear from the test examples described later, the emulsion of the present invention exhibits almost no decrease in content due to decomposition of the main ingredient even when stored at high temperatures for long periods of time, and the emulsion has excellent thermal stability. There is.

Reference Example 1 Pudesonide 0.0253F White Vaseline 35.0jF-
1 =) Stearyl Al Record” 8
．． 0 II cholesterol
2.0. F Sorbitan Sesquioleate
s,oy distilled water total amount 100.
The above ingredients are mixed and stirred in a conventional manner to form an emulsion.

Reference example 2 Budesonide 0.025P microcrystalline wax 6. Op liquid paraffin 1a, op Nuqualan
s, o y sorbitan monostearate) 4.011 isopropyl myristate 2. Op Magnesium Sulfate 0.79 Distilled Water
Total amount 100. Oj' The above components are mixed and stirred in a conventional manner to form an emulsion.

Reference example 3 Budesonide 0.025y Yuro
6.0 liquid paraffin
6.0y white petrolatum
55. OfCholesterol 2.01
monostearyl Δshun glycerin 2.0y sorbitan sesquioleate) 3. Oy distilled water total amount 100. OFThe above-mentioned components are mixed and stirred in a conventional manner to form an emulsion.

Test Examples Each emulsion obtained in the above reference example and the example below was
Table 1 shows the results of measuring the residual rate of the active ingredient using HPLC after storage at 40°C for 1 month, 40°C for 2 months, and 45°C for 1 month, and Table 2 shows changes in the appearance of the emulsion. Each is shown below.

Table 1 Table 2 A: No change k3: Almost no deterioration Next, this invention will be explained with reference to examples.

Example 1 Pudesopoid 0.025y liquid paraffin 200y colored vaseline
20. OF Yurou
5.0y distilled water total amount 10
0. OFThe above-mentioned components are mixed and stirred in a conventional manner to form an emulsion.

Example 2 Budesopoid 0.025F liquid paraffin 20. OjF white petrolatum 15. OF Monosteari Senjun Glycerin 3.0y Propylene Glyco/X15. Of distilled water Total amount 100.0P The above components are mixed and stirred in a conventional manner to form an emulsion.

Example 6 Pudesonide 0.025F liquid paraffin 6. Oy white wax
6. Oy white petrolatum
30.0P74 Crocrystalline wax
5. Oy Crotamiton
3. OF distilled water total amount 100. OF
The above components are mixed and stirred in a conventional manner to form an emulsion.

Patent applicant: Fujisawa Pharmaceutical Co., Ltd.

Claims (2)

[Claims] (1) A water-in-oil emulsion of a steroid drug, characterized by containing polyoxyethylene polyoxypropylene cetyl ether as an emulsifier. (2) The water-in-oil emulsion according to claim 1, wherein the steroid drug is a corticosteroid.