JPH04308530A - Steroid ointment - Google Patents

Abstract

PURPOSE:To obtain an ointment having excellent transcutaneous absorbability and low irritation by compounding a steroidal antiinflammatory agent in combination with a triglyceride and/or a lactic acid ester in an oily ointment base. CONSTITUTION:The objective ointment can be prepared by compounding an oily ointment base with (A) 0.01-2.00wt.% (preferably 0.02-1.00wt.%) of a steroidal antiinflammatory agent such as prednisolone, hydrocortisone, dexamethasone and triamcinolone acetonide (especially preferably dexamethasone acetate) and (B) 0.5-20wt.% (preferably 5-15wt.%) of a 6-12C medium-chain fatty acid triglyceride (preferably straight-chain saturated fatty acid triglyceride) and/or 0.1-20wt.% (preferably 0.5-5wt.%) of a lactic acid ester of a 12-18C aliphatic alcohol (preferably cetyl lactate).

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a steroid ointment that has excellent transdermal absorption and is less irritating.

0002

[Prior Art] Steroid anti-inflammatory drugs do not dissolve in petrolatum, etc., so conventionally they have been prepared as solid dispersion ointments, or as solutions dissolved in glycols, alcohols, etc., dispersed in oily bases. It was used as a droplet-dispersed ointment.

0003

[Problems to be Solved by the Invention] However, solid dispersion ointments have the problem of poor absorption of steroids, which are the main drugs, and low effectiveness, and droplet ointments have problems with skin irritation caused by glycols or alcohols. Stimulation was the problem. Since steroidal anti-inflammatory drugs are often used for skin diseases such as atopic dermatitis, a non-irritating ointment has been particularly desired.

0004

[Means for Solving the Problems] As a result of extensive research to solve the above problems, the present inventors have discovered that a steroidal anti-inflammatory drug is an ester of neutral fatty acid triglyceride and fatty alcohol and lactic acid. The present invention was completed based on the knowledge that they dissolve well and also mix well with oil-based ointment bases.

[0005] The present invention provides an oily ointment base containing 0.01 to 2.00% by weight of a steroid anti-inflammatory drug and 6 to 12 carbon atoms.
A steroid ointment characterized by containing 0.5 to 20% by weight of medium fatty acid triglyceride and/or 0.1 to 20% by weight of an ester of lactic acid with an aliphatic alcohol having 12 to 18 carbon atoms. .

[0006] Examples of steroidal anti-inflammatory drugs used in the present invention include prednisolone, hydrocortisone, dexamethasone, triamcinolone acetonide, fluocinolone acetonide, betamethasone and its esters, with dexamethasone acetate being particularly preferred. The amount of steroid anti-inflammatory drug added is 0.01 to 0.01 of the total weight of the preparation.
2.00% by weight, preferably 0.02-1.00% by weight
It is.

As the medium fatty acid triglyceride having 6 to 12 carbon atoms, linear saturated fatty acid triglycerides, particularly tri(caprylic/capric acid) glycerin, tricaprylic acid glycerin, etc. are preferably used. The amount added is 0
．． 5 to 20% by weight, preferably 5 to 15% by weight. Examples of the ester of an aliphatic alcohol having 12 to 18 carbon atoms and lactic acid include lauryl lactate, myristyryl lactate, cetyl lactate, stearyl lactate, and oleyl lactate, with cetyl lactate being particularly preferred. The blending amount is 0.1 to 20% by weight, preferably 0.5 to 5% by weight.
It is.

[0008] In the ointment of the present invention, either the triglyceride or the lactic acid ester described above can be used, or both can be used in combination.

The oil base used in the present invention is preferably a higher hydrocarbon, such as liquid paraffin, vaseline, paraffin,
Preferably used are ceresin, microcrystalline wax, squalene, or liquid paraffin gelled with polyethylene or dextrin fatty acid ester. The amount used is the remaining amount of the total amount of the steroid anti-inflammatory drug, the triglyceride, and the lactic acid ester.

The ointment of the present invention is prepared by a melt method according to conventional methods. That is, the steroidal anti-inflammatory drug is mixed with the triglyceride and/or the lactic acid ester, heated and dissolved, and then an oily ointment base is added thereto, melted, and gradually cooled while stirring. .

[0011]

Effects of the Invention In the ointment of the present invention, the steroidal anti-inflammatory agent is dissolved in the triglyceride and the lactic acid ester, and this dissolved substance is well mixed with the oil-based ointment base. Excellent absorption through the skin. Furthermore, since the ointment of the present invention does not contain glycols or alcohols, it does not irritate the skin.

0012

EXAMPLES Next, the present invention will be explained in more detail with reference to Examples and comparative test examples.

Example 4 Dexamethasone acetate
0.025g
myristyl lactate
5g
Add white petrolatum to make a total of 1
00g.

Example 5 Fluocinolone acetonide
0.025g
myristyl lactate
5g
Add purified petrolatum to make a total of 100g
shall be.

Example 6 Clobetasol propionate
0.05g
Cetyl lactate
10g
Add white petrolatum to make a total amount of 100 g. Ointments having the formulations shown in Examples 1 to 6 were prepared by the melting method described above.

(Irritation Test) An irritation test was conducted on the ointment of the present invention and a comparative formulation having the following formulation. This preparation is a droplet-dispersed ointment (Pharmacology, vol.
50, 279-291).

Comparative Example 2 A 20% propylene glycol aqueous solution irritation test was carried out by Tetsuro Sugai, "Skin" Vol. 26, No. 4,
The test was performed using the human open chain patch test described on page 767 (1984).

Specifically, samples were applied to the flexor side of the left arm of 20 healthy male volunteers for 48 hours using a patch test plaster (Fin Chamber: Taisho Pharmaceutical Co., Ltd.), and 30 minutes and 24 hours after removal. After a period of time, the measurement was carried out according to the following criteria. No baseline reaction: - slight erythema: ± obvious erythema
:+erythema and edema
:++ Erythema, infiltration, papule, small vesicle: +++ The results were accumulated for each sample, and the positive rate for each determination time is shown in Table 1.

[0019]

[Math 1]

[0020]

[Table 1]

As is clear from the results in Table 1, the ointment of the present invention was found to be a formulation with extremely low irritation.

(Absorption Test) An absorption test of the main drug was carried out according to the test method based on vasoconstriction reaction (Mackenzie test) described in "Today's Skin External Preparations" by Masahiko Takano, Nanzando, 1981, p. 528.

Examples 1 and 2, Comparative Example 1 and Control Ointment (
Approximately 0.02 g of the formulation of Example 1 excluding the main drug)
were randomly placed on a patch plaster (manufactured by Torii Pharmaceutical) and applied to the flexor side of the left arm of 5 healthy men, peeled off after 20 hours, wiped with alcohol cotton, and then applied again after 1, 4 and 8 hours. Judgment was made using the following criteria. FIG. 1 shows a graph in which the vertical axis represents the sum of the scores obtained by each preparation after the evaluation, and the horizontal axis represents the elapsed time after peeling.

In FIG. 1, ◯ indicates the absorbability of Example 1, □ indicates Example 2, ● indicates Comparative Example 1, and △ indicates the absorbability of the control formulation.

[0025] As shown in Figure 1, the ointment of the present invention maintains its anti-inflammatory effect even after 8 hours have elapsed after the patch ointment is removed, and has a better transdermal effect than the ointment of the comparative example. It showed absorbency.

[Brief explanation of drawings]

FIG. 1 is a graph showing transdermal absorption of steroids in steroid ointments.

Claims (1)

[Claims] Claim 1: An oily ointment base containing 0.01 to 2.00% by weight of a steroidal anti-inflammatory drug, 0.5 to 20% by weight of a moderate fatty acid triglyceride having 6 to 12 carbon atoms, and/or the number of carbon atoms. A steroid ointment characterized by containing 0.1 to 20% by weight of an ester of a 12 to 18 aliphatic alcohol and lactic acid.