JPS5843913A - Production of fatty ointment containing steroidal active ingredient - Google Patents

Abstract

PURPOSE:When a fatty ointment containing steroids as active ingredients is prepared, hydroxyethyl salicylate is used as a solvent, thus permitting the production of the above stabilized and less skin-irritating ointment through simple operations. CONSTITUTION:Hydroxyethyl salicylate of the formula is used as a solvent and a steroid preparation such as betamethasone valerate is dissolved in the solvent. When necessary, an oil-soluble solvent such as isocetanol is added to increase the compatibility between the above solvent and the solid to semisolid ointment base. Then, the resultant solution is mixed with the fatty solid ointment base under heating by a usual method to give the objective fatty ointment containing steroids. The addition of the above solvent facilitates the preparation of ointment and cream, improves the percutaneous absorption, stability and skin irritation of the ointment and increases the analgesic and antiinflammatory effect.

Description

[Detailed description of the invention] It is about law.

Conventionally, preparations containing steroid threads, oil and fat properties,
How to blend a liquid surfactant into an oleaginous base and a solvent in the production of a liquid surfactant? A method of blending into an oleaginous base using

However, in the former case, the irritation to the skin is strong, and steroid thread crystals precipitate over time.
The product was not completely satisfactory.

In addition, when oil-based carriers are used as brood media, such as inocetanol, squalane, or teldodecanol, these solvents have low bath solubility for monosteroids, so the amount of water is reduced. Don't mix &tt'L,
In the case of oil-based softeners, the semi-solid component such as petrolatum and the adult component tend to separate, and the problem is that the rebound irritation is strong. In addition, as #1 medium, water-bathable M
94 J Fi 7' When using a bathing medium such as propylene glycol or polyethylene glycol, are these solvents transdermal absorbable? If it is lowered, it is highly irritating to the skin, and in the case of oil-based ointments, it is not compatible with oil and fat components, so it is necessary to mix both in production.
Salmon's advantage was that it was easy to separate even when blended.

Therefore, in order to eliminate these drawbacks, Fubenban et al. carried out extensive research91 with the aim of creating a stable steroid thread oil-based ointment that was not particularly irritating to the skin and found that ethylene glycol salicylate was added to the steroid thread. However, he discovered that it has extremely high solubility and relatively good compatibility with oil-based bases, and completed his invention.

Mtl. The present invention relates to a method for producing an oleaginous ointment containing steroid threads, which is characterized in that ethylene glycol salicylate is used as a solvent in producing the oleaginous ointment using one mulberry of steroid threads.

The present invention has made it possible to obtain a stable oil-based ointment that is easy to manufacture and has low skin irritation.

Examples of the steroid thread used in the present invention include petamethacin valerate, beclomethasone f-lobionate, hydrocortisone acetate, glednisolone, triamcinolone acetonide, fluorometholone, flurandrenolone, and the like.

Ethylene glycol salicylate used in the invention has a boiling point /AV"C ~ /0℃ (/corrr
mH/) colorless viscous paulownia liquid with p specific gravity α: 0 approx.
It is a substance with O1 and anti-inflammatory analgesic effect.

Hereinafter, the method for producing the mIli# soft material of the present invention will be explained.

First of all, is it a steroid drug that is a crude drug? salicylic acid fL/
7 Glycol is commonly understood. In this case, the steroid thread used is photodissolved in glycol salicylate. For example, in the case of betamethacin valerate, 0.0% betamethacin valerate per ml ethylene glycol salicylate. I29, for beclomethasone gropionate, ethylene glycol Q salicylate, g yil
vs. peclomethasone gropionate 0,02! ;
) 'The following appropriate amount of mulberry is dissolved. In addition, due to necessary expenses,
The amount of conventionally used oil-soluble heating media, such as isosetanol and squalane, is adjusted appropriately and used in combination with ethylene glycol salicylate to increase the compatibility between ethylene glycol salicylate and solid bases and semi-solid bases. be able to.

Next, the steroid thread liquid is added to an oil-based type 1 base, such as oils and fats (beeswax, yellow wax, lanolin, etc.), hydrocarbon mixture (fluid I4 rough-in, solid) 9 rough-in, vaseline, squalane, etc.) , higher fatty acids ()lumitic acid,
stearin i1 etc.), -grade alcohols (cetanol,
Stearyl alcohol, etc.) and esters (such as inopropyl lactate, cetyl lactate, etc.) are heated and mixed in a conventional manner to obtain an oil II blind flexure.

As described above, the oily ointment obtained by the uninvented method has a high solubility in steroid drugs of ethylene glycol salicylate, so that it can be easily made into an ointment or cream. Furthermore, since ethylene glycol salicylate ri has excellent transdermal absorption, the light ash absorption of the steroid thread was significantly improved.

In addition, since ethylene glycol salicylate is oil bath-compatible, it has good compatibility with other solid and hostile oil bases, and the stability of the ointment was improved.

Furthermore, since ethylene glycol salicylate has weak skin irritation, it does not use a solvent that is highly irritating to the skin, as is the case with conventional ointments, and the skin irritation can be significantly reduced.

Also, does ethylene glycol salicylate itself have anti-inflammatory and analgesic effects? Therefore, it has many advantages such as being able to enhance the effect of 10 inflammation pain along with the main mulberry steroid thread.

The following is an example of the invention! will be explained in detail.

Example/Ethylene glycol salicylate θ, jl, isosetanol g, ot, microcrystalline wax 3.0? ,
White petrolatum, weighing 173ft, 200m1
Pour it into a beaker, add the distilled beclomethasone propionate, oas'tw, and dissolve it in a water bath at θ℃. Stir to make it homogeneous, then remove it from the water bath, remove the stone, cool it to room temperature, and make it semi-solid and oily. I got the ointment.

Example: Ethylene glycol cosalicylate θ1g? , isosetanol t, Of, microcrystalline wax S, Ot,
White petrolatum gt, weighed on an ogvr scale, placed in a 200114 beaker, and petamethacin valerate 0 was accurately weighed into this.
．． /Ko? After adding it to the water temperature and stirring to make it homogeneous at around gO ℃, remove it from the water bath and leave it to cool to room temperature.
One oily ointment was obtained for the body.

Example 3 This example was obtained from Example 1 and Example λ, and fc? 11 shows a fatty softening action.

Kenzie Matsu (McKenzl@) et al. Archive Dermatology (^rch, Derm), 31. Volume, 60
This test was carried out in 2013 by a method similar to that of Cao Bishu. That is, the following samples ^, B, C, and D'i were applied to the upper backs of 10 healthy male adults, and the vasoconstriction effect was evaluated and determined as the Kinpaku phenomenon.

This judgment is 1-(-) with no reaction at all, slight pallor (±
), clearly one & R whitening meeting (+).

Sample ^: # in Example 1! Ointment B: Example/Ethylene glycol salicylate? Commercially manufactured ointment C: Ointment D manufactured in Example C = Actual implementation Ointment manufactured by removing cocosalicylic acid ethylene glycol Put it on the table.

EXAMPLE This example shows a test example of the skin stinging properties of the oily ointments produced in Example 1 and Example 2.

This test was conducted using the Nobutsuchi test. That is, the same sample as in Example 3 was patched on the upper backs of 70 healthy male adults for a period of 4 hours, and the degree of irritation to skin dandruff was observed after 4 hours and after 4 hours. I judged it. The test results are shown in Table λ.

In addition, the judgment and criteria were in accordance with the original Japanese standard.

No response (-) 0 points Slight erythema (±>O, S points Obvious erythema (+) 7 points Erythema + papules or edema (++) 1 point The score was calculated using the above formula.

As is clear from the table and table, the oil-based ointment obtained by the method of the present invention has an excellent vasoconstrictive effect and a skin-constricting effect. It was a weak irritant.

Claims (1)

[Claims] Is it possible to use ethylene glycol salicylate as a solvent when manufacturing an oil-based ointment using steroid thread as the main ingredient? A method for producing an oil-based ointment containing steroids, characterized by: