|Publication number||US2504482 A|
|Publication date||Apr 18, 1950|
|Filing date||Jun 17, 1949|
|Priority date||Jun 17, 1949|
|Publication number||US 2504482 A, US 2504482A, US-A-2504482, US2504482 A, US2504482A|
|Original Assignee||Premo Pharmaceutical Lab Inc|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (3), Referenced by (46), Classifications (9)|
|External Links: USPTO, USPTO Assignment, Espacenet|
Apnl 18, 1950 R. GOLDMAN 2,504,482
DRAIN-CLEAR CONTAINER FOR AQUEOUS-VEHICLE LIQUID PHARMACEUTICAL PREPARATIONS Filed June 17, 1949 THIN TRRNSPI-fkavr Sll. ICONE Fu. M
J'NVENTOR. Ragsnr GOLDMHN BY Patented Apr. 18,. 1950 FlCE DRAIN-CLEAR CONT GUS-VEHICLE LIQ PREPARATIONS Robert Goldman, Brooklyn, N.
Premo Pharmaceutical South Hackensack, N. J., a corporation of York mm FOR AQUE- UID PHARMACEUTICAL Y., assignor to Laboratories, Inc., New
Application June 17, 1949, Serial No. 99,888
1 Claim. 1
This invention relates to drain free containers for aqueous liquid pharmaceutical preparations (hereinafter referred to as aqueous pharmaceuticals) It is well known that when an aqueous pharmaceutical is emptied from a container a film of the pharmaceutical adheres to the container walls.
The wastage represented by the retained film may tity of the aqueous pharmaceutical to make certain that the prescribed dosage would be dispensed. For example, for a dosage of 1 cc. of procaine penicillin to be given parenterally, it was customary to add to the pharmaceutical in the 4 cc. vial or ampoule an extra -25% to be sure that a 1 cc. injection would be obtained. In this instance, about 17% of the extra quantity was present because of the retained film, the remainder of the extra quantity being present for other reasons with which the present invention is not concerned. The same practice of providing an extra percentage of the pharmaceutical was followed with multiple dosage containers so that the user could withdraw from the container the full amount which the label indicated.
Another disadvantage of the retained film is that it makes the container unattractive and creates difficulty in determining the amount of pharmaceutical remaining.
It is an object of my invention to provide for aqueous pharmaceuticals a container having none of the foregoing disadvantages.
More specifically, it is an object of my invention to provide a clear-draining container for aqueous pharmaceuticals.
Other objects of my invention will in part be obvious and in part will be pointed out hereinafter.
In the accompanying drawing, in which is shown one of the various possible embodiments of my invention, the single figure is a plan view, partially broken away, of a bottle constructed in accordance with my invention.
In general, I carry out my invention by providing a pharmaceutical container with an internal surface which has been rendered waterrepellent by silicone treatment. By pharmaceutical container, I refer to any type of enclosure which can receive and hold an aqueous pharmaceutical. Typical of such containers are vials, bottles, ampoules, hypodermic syringes, pipettes and burettes. By silicones, I refer to organopolysiloxanes, i. e. organo-silicon oxide polymers.
In practicing the invention, a silicone carried in a vaporizable liquid vehicle is applied to the internal surfaces to be treated, as for example by rinsing the inside of a container with a liquid constituting a silicone dissolved or dispersed in a liquid vehicle. Thereafter the vehicle is evaporated, thus leaving a very thin transparent film of the silicone. Said film is water-repellant, so that when a container thus treated, and containing an aqueous pharmaceutical, has its contents emptied, the film which normally would remain on its internal surfaces contracts into globules which fall toward the bottom of the container and leave the walls clean.
More specifically, the invention is achieved by dissolving a silicone in an organic solvent such as chloroform or ether. The composite fiuid, solvent and solute, is introduced into a container. Thereafter the composite fluid is drained out leaving a film thereof on the inner wall of the container. The solvent in this film is permitted to evaporate. Optionally, the evaporation may proceed at room temperatures, and satisfactory results are secured in such fashion. However,
particularly good results are obtained where the solvent not only is evaporated but the residual film of silicone is heat treated to bake the same. Such heat treatment consists in elevating the temperature of the container to any point above room temperature and below a temperature at which the silicone vaporizes from the container surface. In general, the higher the temperature employed, the less time is required for baking. The actual temperature used is not critical. It is believed that the silicone layer is molecularly fused to the walls of the container, particularly when the container is glass.
Organo-polysiloxanes which function satisfactorily in the practice of my invention are of the formula where n is any integral number and R is any single alkyl or aryl group or combination thereof, that is to say different R groups may be combined in a single organo-polysiloxane to add up to the total number of R groups required by the formula. The alkyl groups may be saturated or unsaturated and examples thereof are methyl, ethyl, propyl, butyl, amyl, hexyl, heptyl, octyl,-decyl., dodecyl, vinyl and allyl. Examples of the aryl group are phenyl, toluyl and naphthyl.
Satisfactory silicones are:
Hexamethyl disiloxane (CH3)eSi2O Dodecamethyl pentasiloxane (CHs)12Si5O4 Methylphenylpolysiloxane (CH3) :(CsHs) (21l+2)-.'lsinonl so where :c is any integral number less than 2n+2.
Other satisfactory silicones have the same formulae except that for the methyl groups in the first two silicones and for the methyl and phenyl groups in the last silicone any other aryl or al-' kyl groups can be substituted. Actual listing of these other silicones has been omitted for the sake of brevity.
It may be mentioned that in commercial silicones n reaches very high values and the chain is so long that the values of n are not used to denote the compounds, but rather physical properties are employed for this purpose. The physical property commonly employed is viscosity. I have found silicones of all viscosities to be operable in the practice of my invention-even as high as 100,000 centistokes.
By way of example and without limiting my invention thereto, the following constitutes a specific embodiment of a composite fluid with which I have secured very good results:
1 part by weight methyl silicone fluid viscosity 50 centistokes 99 parts by weight of chloroform A suitable baking time is one-half hour at 300 C. or nine hours at 180" C.
Where other silicones are employed the same percentage by weight can be used and the same baking temperature and time provided that the temperature does not exceed that at which the silicone will vaporize from the container surface.
Inasmuch as the water-repellent silicone film is transparent, the best visual results are obtained when the container likewise is transparent, being fabricated, for example from glass. This permits the contents of a partially empty container always to be very clearly visible and is in particularly marked contrast to the appearance of similar untreated containers. It should be observed that drain-clear containers are specially useful in connection with pharmaceutical preparations, due to the high price which usually prevails for such preparations and to the large amounts of such preparations that are packaged throughout a year.
A film applied in the manner described is so thin that its thickness is measured in hundreds of molecules.
When a drain-clear container is employed, a manufacturer can materially reduce the extra amount of pharmaceutical added to a container in order to/make certain that the physician, technician or patient will withdraw the proper amount when the entire contents of the container is to be used as a single dose. Moreover. the user is able to secure a highly accurate dosage which up to now could not be done without measurement, inasmuch as the actual percentage retained in the bottle by way of a film varies widely with the particular constitution of the preparation and with the temperature. The manufacturer likewise can eliminate the addition of the amount normally added to multidose containers because of a retained film.
By way of example, through the use of my invention the excess percentage of aqueous suspension procaine penicillin for a 15 cc. vial containing 5 one cc. doses can be reduced from 22% to and for a 4.5 cc. vial containing one 1 cc. dose from 22% to 5%.
An alternative method of applying a trans parent silicone layer is to wet the interior surface of a container and then expose said surface to vapors of organo-silicon halides.
More specifically, this alternative procedure is effected by first exposing the interior surface of a container, e. g. a glass vial, to moisture, for
instance by steaming the vial. While the inside 5 ol' the bottle still is moist, a vapor of methylchlorosilane is introduced as a pure or substantially pure gas. The absorbed moisture in the glass reacts with the methylchlorosilane to liberate methyl silicone which forms as a thin layer on the interior surface of the container. Hydrogen chloride is formed as a by-product.
This process can be carried out by limiting introduction of the steam and methylchlorosilane vapor to the interior of the container or, alternatively, by placing the container in a closed chamber where water vapor and methylchlorosilane vapor successively are introduced.
It may be noted that in the latter case the external as well as the internal surface of the container is rendered water-repellent and in such case, unless a portion of the external surface previously is treated, as by the application of a protective layer of a substance which subsequently is stripped off, it will be difiicult, if not impossible, thereafter to adhere a label or the like to this surface.
If it is desired to reuse a container whose internal surface has been silicone treated in accordance with any of the foregoing processes, the same may be washed either with water, or soap and water, without affecting the transparent silicone film.
In the drawing, I have shown a pharmaceutical container constituting a transparent bottle I0 whose internal surface has been coated, as aforesaid, with a thin. transparent silicone film l2, so as to render the interior water-repellent. As noted heretofore, the film is extremely thin. However, its thickness has been increased, as illustrated in the drawing, so that a reference numeral can be applied thereto. The bottle is filled with an opaque, aqueous-vehicle liquid pharmaceutical l4, such for example as procaine penicillin in aqueous suspension.
It thus will be seen that I have provided a container which achieves the several objects of my invention and is well adapted to meet the conditions of practical use.
As various possible embodiments maybe made of the above invention, and as various changes might be made in the embodiment above set forth, it is to be understood that all matter herein described is to be interpreted as illustrative and not in a limiting sense.
Having thus described my invention, I claim as new and desire to secure by Letters Patent:
A clear draining dispensing container of transparent material filled with an opaque aqueousvehicle liquid pharmaceutical preparation, said 00 container having a thin transparent silicone film on its internal surface whereby when said pharmaceutical preparation is dispensed the container will drain clear.
REFERENCES CITED The following references are of record in the file of this patent:
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|U.S. Classification||604/403, 206/524.3, 260/DIG.470, 215/DIG.600|
|Cooperative Classification||Y10S215/06, Y10S260/47, B65D23/02|