JPS59217784A - Aerosol suspension - Google Patents

Abstract

PURPOSE:The titled suspension having improved suspending and dispersing properties, and stability in a wide temperature range, containing a liquefied propellant, solid powder insoluble in it, octyldodecyl oleate, octyldodecyl ricinoleate, etc. as a suspension. CONSTITUTION:The desired suspension containing preferably 50-95wt% liquefied propellant (e.g., trichlorofluoromethane, etc.), 0.5-15wt% solid powder (e.g., talc, benzethonium chloride, etc.) insoluble in it, 0.05-15wt% octyldodecyl oleate shown by the formula I (R is group shown by the formula II), octyldodecyl ricinoleate shown by the formula III and/or octyldodecyl myristate shown by the formula IV as a suspension, and, if necessary, 5-40wt% solvent, to give the desired suspension. EFFECT:Mild to the skin, free from optical toxicity and dangerous toxicity, having no irritation to eye mucosa. USE:Drugs, guasi-drugs, cosmetic, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an aerosol suspension with improved suspension dispersibility.

A solid powder that is insoluble in the liquefied propellant is suspended and dispersed in the liquefied propellant using a surfactant or a suspending agent, and this is filled into a pressure-resistant container and fired from the injection hole or nozzle of the container. It is known to inject. However, aerosol products filled with aerosol suspension agents, -! , there are various problems. For example, in niazole suspensions, it is generally difficult to sufficiently suspend and disperse solid powders such as drugs intended for spray application in the liquefied propellant, and the stability of the suspension state is low. Suspended particles become sedimented, suspended or agglomerated. As a result, injection holes, nozzles, valves, or actuators become clogged, or uniform spraying becomes obstructed, and the efficacy of the drug is also significantly affected, making it impossible to obtain the desired medicinal efficacy. This tendency becomes more pronounced when the amount of solid powder to be suspended is large. This is because solid powder particles immediately separate or agglomerate after the suspension operation, except in special cases.

Therefore, in aerosol suspensions, it is necessary to sufficiently suspend and disperse the solid powder using an appropriate suspending agent and maintain that state stably. It is necessary to prevent adhesion to container walls, formation of precipitates, and adhesion of precipitates.
÷There is.

The following methods are known for obtaining an aerosol suspension by suspending a solid substance that is insoluble or poorly soluble in a liquefied propellant.

(1) Hrfi (,'-aqueous, lipophilic equilibrium value)
A method of suspending a solid substance in a liquefied systemic agent using a liquid non-ionic surfactant whose angle is about 1° or less and which is not the same as that of a liquefied propellant (Japanese Patent Publication No. 14697/1983) reference)
.

(2) A method of dispersing insoluble solids in a liquefied propellant using lecithin, lanolin, cholesterol, or their derivatives dissolved in lower alcohol and higher fatty acid esters (Japanese Patent Publication No. 40-28956) reference).

(6) Using natural phospholipids and 6-phosphate esters that are soluble in liquefied propellant, and a higher alcohol having a linear side chain and having 11 to 20 carbon atoms and which is liquid at room temperature,
A method of suspending a solid substance in a propellant (“Special Publication Act
(See Publication No. 804).

(4) A method of suspending insoluble solids in a liquefied propellant using a liquid acetylated product of a partial ester with a long chain fatty acid of a polyhydric alcohol
(See Publication No. 409).

However, none of these methods produces satisfactory results. These methods do not always provide a sufficiently stable suspension/dispersion state, and the types of suspending agents and solid materials that can actually be used are limited. Therefore, it is often difficult to apply conventional methods to aerosols for the human body, which should avoid the use of substances that are highly irritating to the skin. For example, when solid particles are suspended and dispersed with an ester, isopropyl myristate or isopropyl illumitate has been mainly used as the ester, but these are highly irritating to the skin, have a pungent odor, and are sticky. There are drawbacks.

In order to improve this point, the present inventor conducted various studies and found a suspending agent that can suspend and disperse many types of solids and provide a stable suspension. completed.

The present invention provides liquid/condensed propellant, self-insoluble solid powder,
and an aerosol suspension characterized by containing octyldodecyl oleate, octyldodecyl lysyloleate, and/or octyldodecyl myristate as a suspending agent.

The aerosol suspension of the present invention may optionally contain a solvent such as ethanol, a compressed gas such as carbon dioxide, nitrogen, -nitrogen oxide, helium, etc. When containing a solvent, the composition of the suspending agent is 0.5 to 15% by weight of solid powder;
Suspending agent 0° is preferable.

Octyldodecyl oleate (A), octyldodecyl lysylinate (B) and octyldodecyl myristate (C) used as suspending agents are represented by the following formula. R in these formulas is CH2-C,H.

-CH2-CH-C, oH2□ shows.

CH3-(CH2)7-cH=cH-(CH2)7-c
oo-R(A)CH CH3-(CH2), -CH-CH2-CH=CH-(
CH2)7-Coo-R(B)CH3-(CH2),2
-Coo-R' (C) In addition to being excellent as a suspending agent, these compounds have the following characteristics. It causes almost no skin irritation, provides lubricity and flexibility to the skin, and has anti-aging and bactericidal effects. It also has a very good feel when applied to the skin, is non-sticky, has excellent spreadability, is light and has an absorption window, blends well, has a porosity effect, is stable on the skin, and decomposes. It has almost no odor or color, and does not change color or odor over time. It has a moderately low viscosity, is economical, and is not decomposed by microorganisms on the skin (and has low solubility in fragrances. Because it is a large solvent with a high molecular weight, it has a slow permeability through the epidermal barrier and is useful for alleviating the skin irritation caused by fragrances.

It does not become rancid as seen in cosmetic oils used for the skin, mucous membranes, hair, scalp, etc., and is stable against temperature and light, and has good heat resistance. It is also possible to mix pairs of solvents. In particular, it prevents color separation of pigments and has excellent spreadability.

In particular, it is liquid at room temperature, has a low freezing point, and high boiling and flashing points (it is stable even in air without being oxidized).

Examples of the solid powder include the following.

Prednisolone, hydrocortisone and their derivatives, dexamethasone, tetrahydrozoline hydrochloride, fradiomycin sulfate, benzethonium chloride, aluminum powder, kaolin, Merck, aluminum chlorohydroxide powder, titanium oxide, magnesium carbonate, magnesium silicate, fish scale foil , mica titanium, mica,
Starch, synthetic polymers such as nylon, polyethylene, etc., stearic acid magnesium salts, calcium salts, aluminum salts, etc., iron oxides such as red iron oxide, bentonite, colored pesto, silver powder, etc. These powders preferably have a particle size of 100 microns or less, particularly 5 to 60 microns.゛As the liquefied propellant, for example, trichlorofluoromethane (Fll), dichlorodifluoromethane (Fl2), chlorofluoromethane (-F22), 1,2-dichloro-1,1,2,2
-Tetrafluoroethane (Fll4), 1,1.2-)
Dichloro-1,2,2-)lifluoroethane (Fl 1
3), 1-chloro-1,1-difluoroethane (F1
42b), dimethyl ether (DME), liquefied petroleum gas (LP()), etc. are used.

The aerosol suspension of the present invention can be obtained by filling a fine solid powder and a suspending agent together with a liquefied propellant under pressure in a pressure-resistant container and thoroughly mixing them. In this case, appropriate auxiliaries or additives may also be added.

The aerosol suspension of the present invention is extremely stable, and even if left for a long time, the powder particles hardly settle, float, or aggregate. In addition, solid matter can be easily dispersed, and a stable suspension and dispersion state can be maintained over a wide temperature range.

The aerosol suspension of the present invention is suitable as an aerosol for human bodies such as medicines, quasi-drugs, and cosmetics. That is, octyldodecyl oleate used as a suspending agent,
Octyldodecyl lysylpentate and octyldodecyl myristate are mild to the skin, have no phototoxicity or dangerous toxicity, are not irritating to the eye mucous membrane, and are harmless or non-toxic to the human body. In addition, it is non-sticky to the skin, spreads well, provides lubricity and flexibility, and has anti-aging, moisturizing, and bactericidal effects. Its compatibility with the skin is superior to lanolin and the like, and it is odorless and does not cause discomfort.

Examples 1 to 15 Aerosol suspension preparations containing the ingredients shown in the table below were manufactured, and redispersibility, fluidity, pulp and clogging tests were conducted using the preparations.

The redispersibility is 5% in a low atmosphere at a temperature of 35°C and a humidity of 60%.
After being left for a month, the degree of dispersion was determined as follows.

◎: Uniformly dispersed △: Strong tendency to agglomerate ×: Strong agglomerates were formed in some parts ′ Fluidity was determined by shaking a glass bottle filled with the sample in an upright position, and determining the fluidity of the contents as follows. .

◎: Content moves a lot △: Slight movement ×: Does not move 50 samples were used in the pulp clogging test, and the number of pulp clogging is shown in the table.

Suspending agent A in the table is oleic octyldodecyl, B
represents octyldodecyl lysylinate, and C represents octyldodecyl myristate.

-15- Applicant: Toyo Air Sol Industrial Co., Ltd.

Claims (1)

[Scope of Claims] 1. An aerosol containing a liquefied propellant, a solid powder insoluble therein, and octyldodecyl oleate, octyldodecyl lysylinate, and/or octyldodecyl myristate as a suspending agent. Suspending agent. 2. Liquefied propellant 50-95% by weight, solid powder 0°5
15. An aerosol suspension according to claim 1, containing from 15% to 15% by weight of a suspending agent, from 0.05 to 15% by weight of a suspending agent and optionally from 5 to 40% by weight of a solvent.