JP2004307515A - External anti-inflammatory preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an anti-inflammatory preparation which has anti-inflammatory effects equal to those in oral administration while reducing cutaneous stimulation in an ointment, a cream, or a liquid drug containing indomethacin. <P>SOLUTION: The preparation is an ointment, a cream, or a liquid drug contains 0.5-1.5 wt% indomethacin, 1-10 wt% percutaneous absorption accelerator such as diisopropyl adipate, and 0.5-5 wt% vitamin E or vitamin E acetate. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  Indomethacin, a non-steroidal anti-inflammatory analgesic, is generally used in the field of orthopedic surgery because of its excellent anti-inflammatory action. However, indomethacin may have severe side effects on the digestive tract in the case of oral administration and the rectum in the case of suppositories. Therefore, in order to reduce side effects of indomethacin, topically applied preparations such as ointments, liquid preparations, and poultices have been developed. These topical preparations contain fatty acid esters, alcohols, terpenes and the like as a transdermal absorption enhancer of indomethacin in order to obtain the same pharmacological effect as the oral preparations.

JP-A-2-142727 JP-A-2-196718

  Transdermal absorption enhancers enhance the transdermal absorbability of drugs, but these absorption enhancers have skin irritation properties because they reduce skin barrier properties. In general, the higher the effect of promoting percutaneous absorption, the higher the skin irritation. However, in order to obtain the same pharmacological effect as that of an oral preparation, it is necessary to incorporate a large amount of a transdermal absorption enhancer, and there is still a problem in practicality.

  The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, by adding vitamin E or vitamin E acetate to an anti-inflammatory analgesic external ointment, cream and solution containing indomethacin, the anti-inflammatory effect of indomethacin is improved. They have found that they can be used safely and have completed the present invention.

  That is, the present invention provides the same antiphlogistic and analgesic effect as in the case of oral administration by adding a transdermal absorption enhancer and vitamin E or vitamin E acetate to an antiphlogistic / analgesic external preparation containing indomethacin, and provides skin irritation. It provides a reduced formulation. The amount of indomethacin used in the present invention is preferably 0.5 to 1.5% by weight, and the amount of vitamin E or vitamin E acetate is preferably 0.5 to 5% by weight. Transdermal absorption enhancers include fatty acid esters such as isopropyl myristate, isopropyl palmitate, diethyl sebacate, diisopropyl sebacate, and diisopropyl adipate; alcohols such as ethanol, propylene glycol and polyethylene glycol; and terpenes such as menthol. can give. A more preferred transdermal absorption enhancer is diisopropyl adipate, and the compounding amount is desirably 1 to 10% by weight.

  The anti-inflammatory and analgesic external preparation containing indomethacin, vitamin E or vitamin E acetate and a transdermal absorption enhancer obtained by the present invention is excellent in percutaneous absorption and has no skin irritation, and has muscle pain, back pain, joint pain, tendonitis, bruise It is useful as a therapeutic agent in orthopedic fields such as sprains.

  Hereinafter, the present invention will be described specifically with reference to Examples and Test Examples.

Example 1
To 0.75 g of indomethacin, 2 g of vitamin E acetate, 3 g of diisopropyl adipate, 25 g of medium-chain fatty acid triglyceride, 6 g of Nichol (TS-10), 3 g of Nichol (SS-10) and 8 g of Nichol (MGS-DEX) were added, and the mixture was heated to 75 ° C. Heated to dissolve. Next, 10 g of propylene glycol, 0.1 g of citric acid and 0.05 g of sodium citrate were dissolved in 42.1 g of water, and this and the above solution were stirred until homogeneously emulsified to obtain a cream.

Example 2
To 0.75 g of indomethacin, 1 g of vitamin E acetate, 10 g of diisopropyl adipate, 4 g of Nichol (TS-10), 2 g of Nichol (TS-30), 3 g of Nichol (SS-10) and 0.1 g of dibutylhydroxytoluene were added, and 70 ° C. To dissolve. Next, 0.2 g of l-menthol was dissolved in a mixed solution of 35 g of ethanol and 43.95 g of water, and this solution and the above solution were stirred until homogeneously emulsified to obtain a liquid preparation.

Comparative Example 1
To 0.75 g of indomethacin, 3 g of 1-menthol, 5 g of Nikkor (TS-10), 5 g of diisopropyl adipate, and 10 g of isopropyl myristate were added and heated to 75 ° C. for dissolution. A liquid obtained by swelling 0.8 g of carboxyvinyl polymer in 65.05 g of water was added to this solution, and the mixture was stirred and emulsified. Next, 0.4 g of diisopropanolamine was dissolved in 10 g of water, and this and the above-mentioned emulsion were stirred until uniform to obtain a cream.

Comparative Example 2
To 3 g of liquid paraffin, 0.5 g of Nikkor (TS-10) was added and stirred at room temperature to dissolve. A liquid obtained by swelling 1 g of carboxyvinyl polymer in 85 g of water was added thereto, followed by stirring and emulsification. Next, a solution prepared by dissolving 0.5 g of diisopropanolamine in 9.25 g of water was added and stirred. Then, 0.75 g of indomethacin was added and the mixture was stirred until it was uniformly dispersed to obtain a cream.

Test example 1
The preparations obtained in Example 1 and Comparative Example 1 were subjected to a primary skin irritation test by the Draziz method (Hideoki Ogawa et al., New Physiology and Safety of Skin, 1983) using four rabbits. As a result, the skin primary irritation index of Example 1 and Comparative Example 1 was 0.5 and 0.9, respectively, and Example 1 had less skin irritation caused by the transdermal absorption enhancer than Comparative Example 1. I was

Test example 2
For the preparations obtained in Example 1, Comparative Example 1 and Comparative Example 2, bruise, sprain, muscle pain, back pain, joint pain, tendonitis (hand and wrist pain), elbow pain (tennis elbow, etc.), and stiff shoulder A clinical trial was conducted on 53 complaining patients. Instructed to apply an appropriate amount to the affected area several times a day, up to four times a day, as a dosage and administration. In addition, the administration period was basically 2 weeks. However, when healing was completed within 2 weeks, the treatment was terminated, and evaluation was performed at that time. The evaluation was based on four levels of "severe", "moderate", "mild", and "no symptoms" for spontaneous pain, tenderness, motor pain, swelling, local warmth, and exercise restriction due to pain as subjective and objective symptoms. After observation, the degree of improvement for each symptom at the end of the administration was compared with that at the start of the administration. The results are shown in Table 1 as the degree of overall improvement (%). Thus, Example 1 and Comparative Example 1 in which the percutaneous absorption promoter was blended were more effective than Comparative Example 2 in which no percutaneous absorption promoter was blended.

  The present invention relates to an anti-inflammatory and analgesic external preparation containing indomethacin as an active ingredient. More particularly, the present invention relates to an external preparation containing vitamin E or vitamin E acetate and exhibiting an excellent anti-inflammatory and analgesic effect.

Claims (1)

An antiphlogistic analgesic external preparation characterized by comprising vitamin E or vitamin E acetate in an ointment, cream or liquid containing indomethacin.