JPH0244350B2 - - Google Patents

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 have various problems. For example, in aerosol suspensions, it is generally difficult to sufficiently suspend and disperse a solid powder such as a drug intended for spray application in a liquefied propellant, and the stability of the suspended 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 to maintain this state stably, thereby preventing the particles from settling. It is necessary to prevent floating, agglomeration, etc., adhesion to container walls, formation of precipitates, and adhesion of precipitates. 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) Suspend solids in the liquefied propellant using a liquid nonionic surfactant that has an HLB (hydrophilicity/lipophilic balance value) of approximately 10 or less and is insoluble in the liquefied propellant. Method (see Japanese Patent Publication No. 36-14397). (2) A method of dispersing insoluble solids in a liquefied propellant using lecithin, lanolin, cholesterol, or a derivative thereof dissolved in an ester of a lower alcohol and a higher fatty acid (Tokuko Showa)
(See Publication No. 40-28956). (3) Using natural phospholipids and phosphoric acid esters that are soluble in liquefied propellants, and higher alcohols with 11 to 20 carbon atoms that are liquid at room temperature and have linear side chains, solid materials can be A method of suspending in propellant (see Japanese Patent Publication No. 14804/1983). (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 Japanese Patent Publication No. 41-409) . 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 palmitate has been mainly used as the ester, but these have disadvantages such as strong irritation to the skin, a pungent odor, and stickiness. There is. As a result of various studies to improve this point, the present inventor discovered a suspending agent that can suspend and disperse many types of solids and also provide a stable suspension, and completed the present invention. did. The present invention provides an aerosol suspension characterized by containing a liquefied propellant, a solid powder insoluble therein, and octyldodecyl oleate, octyldodecyl ricinoleate, and/or octyldodecyl myristate as a suspending agent. It is. The aerosol suspension of the present invention may optionally be prepared using a solvent such as ethanol, a compressed gas such as carbon dioxide, or a compressed gas such as carbon dioxide.
It may contain nitrogen, nitrogen monoxide, helium, etc. When containing a solvent, the composition of the suspending agent is 0.5 to 15% by weight of solid powder, 0.05 to 15% by weight of suspending agent,
Especially 0.1 to 7% by weight, liquefied propellant 50 to 95% by weight,
5 to 40% by weight of solvent is preferred. Octyldodecyl oleate (A) and octyldodecyl ricinoleate (B) used as suspending agents
and octyldodecyl myristate (C) is represented by the following formula. R in these formulas is shows. CH ₃ −(CH ₂ ) ₇ −CH=CH−(CH ₂ ) ₇ −COO−R
(A) _CH3- ( _CH2 ) ₁₂ -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 an excellent feel when applied to the skin, is non-sticky, has excellent spreadability, feels crisp and absorbent, blends well, has a porosity effect, and is stable on the skin and decomposes. There is no odor, almost no color,
Does not change color or change odor over time. The viscosity is moderately low, the price is economical, there is no decomposition by microorganisms on the skin, there is a high solubility in fragrances, and since it is a solvent with a large molecular weight, the epidermal barrier permeation is slow, and fragrances do not irritate the skin. Helpful for relief. There is no rancidity that occurs in cosmetic oils used for skin, mucous membranes, hair, scalp, etc., and temperature,
It is stable against light and has good heat resistance. It is also possible to mix them by applying them to a pair of solvents. In particular, it prevents color separation of pigments and has excellent spreadability. In particular, it is liquid at room temperature and has a low freezing point.
It has a high boiling point and flash point, and 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, talc, aluminum chlorohydroxide powder, titanium oxide, magnesium carbonate,
Magnesium silicate, fish scale foil, titanium mica, mica, starch, synthetic polymers such as nylon, polyethylene, etc., magnesium salts, calcium salts, aluminum salts of stearic acid, 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 30 microns. Examples of liquefied propellants include trichlorofluoromethane (F11), dichlorodifluoromethane (F12), chlorofluoromethane (F22), 1,2-
Dichloro-1,1,2,2-tetrafluoroethane (F114), 1,1,2-trichloro-1,2,
2-trifluoroethane (F113), 1-chloro-
1,1-difluoroethane (F142b), dimethyl ether (DME), liquefied petroleum gas (LPG), 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, powder particles will not settle or float.
Almost no aggregation occurs. 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. In other words, octyldodecyl oleate, octyldodecyl ricinoleate, and octyldodecyl myristate, which are used as suspending agents, are mild to the skin, have no phototoxicity or hazardous toxicity, are not irritating to the eye mucous membranes, and are safe for the human body. It is harmless or non-toxic. 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, flowability and valve clogging tests were conducted using the preparations. The redispersibility is 5% in an atmosphere with a temperature of 35℃ and a humidity of 60%.
After leaving it for a month, the degree of dispersion was determined as follows. ◎: Uniformly dispersed △: Strong tendency to agglomerate ×: Strong agglomerates formed locally Fluidity is determined by shaking the glass bottle filled with the sample lightly in an upright position, and determining the fluidity of the contents as follows: did. ◎: The contents move a lot △: Slightly move ×: Not move The valve clogging test used 50 samples, and the number of valve clogging is shown in the table. Suspending agent A in the table represents octyldodecyl oleate, B represents octyldodecyl ricinoleate, and C represents octyldodecyl myristate.

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Claims (1)

[Scope of Claims] 1. An aerosol suspension characterized by containing a liquefied propellant, a solid powder insoluble therein, and octyldodecyl oleate, octyldodecyl ricinoleate, and/or octyldodecyl myristate as a suspending agent. Clouding agent. 2 Liquefied propellant 50-95% by weight, solid powder 0.5-95% by weight
15% by weight of suspending agent, 0.05-15% by weight of suspending agent and optionally 5-40% by weight of solvent.