US 2381621 A
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Description (OCR text may contain errors)
Aug; 7, 1945.
F. c. SCHMELKES EIAL COMPOSITE THERAPEUTIC FILM FiIed Aug. 22, 1942 IN VEN TORS Want? 6: St/mal/fesayfimrnk 1a delmw FITTORNEY Patented Aug. 7, 1945 COMPOSITE THERAPEUTIC FILM Franz C. Schmelkes, Montclair, N. 1., and Frederik J. G. de Leeuw, East Aurora, N. E, as-
H signers to Wallace & Tiernan Products Inc.. a
corporation of New Jersey Application August 22, 1942 Serial No. 5,975
This invention relates to a therapeutic article in the form of a film and particularly to such an article adapted for applying to a moist lesion two or more medicinals which, while chemically incompatible, react with each other only relatively slowly.
' Application of two or more therapeutic agents at the same time or in sequence isoften desirable. Such instances are the use of two germicides, a germicide and a local anaesthetic, or an anti-bacterial substance and a tissue growth stimulant. Preparations such as solutions, jellies, and ointments containing two or more therapeutic agents are frequently impractical, particularly when chemical reaction between the various constituents reduces the shelf life oi such multiple preparations.
The present invention provides a stable medicating article containing two or more therapeutic agents that may be chemically incompatible and permits their simultaneous application in an effective, convenient and simple manner. I
The invention comprises a therapeutic article including a hydrophilic base material and a plurality of water soluble medicinal substances distributed in the base material. The major proportions and preferably, practically all of the said substances are isolated from each other by the base material extending between the said substances, this arrangement being particularly advantageous in those cases where the medicinal substances are slowly interreactive and injurious to each other on relatively long contact. In the preferred embodiment, the invention comprises loss of activity but that are not so quickly reactive as to destroy each other to anobjectionable I extent in the relatively short period of time dur ing which the incompatible substances are ditiusing from the composite and into-the body tissue when the composite is in use in a moist or weeping lesion.
The invention will be illustrated by descrip-- tion in connection with the drawing to which reference is made. v
Figs. 1, 2, 3 and 4 show sectional views of the article of the present invention, the thickness being somewhat exaggerated in comparison with the other dimensions.
a plurality of pliable substantially dry films and incompatible medicinals disposed separately in the several films so that no one film will contain substances that are incompatible with each other. In another embodiment, the invention comprises such a therapeutic film containing a spacing layer, as of fabric or a thin non-medicated plastic or cementing layer that is readily penetrated by water, extending between adjacent ones of the plurality of plies and maintaining the plies out of contact with each other. Preferably the one of the plies that is to be next to the lesion when the composite is in use is relatively very thin, so as to offer a minimum of resistance to diffusion between the other ply and the lesion.
With a composite of the kind described, excellent results have been obtained in the application of two or more medicating materials that, when maintained in long contact with each other as in solution in the same film, undergo There are shown in Fig. 1 a plurality of films 2 and 4 and in Fig. 2 like films with a cementing material 6 adhering the films together. In the structure of Fig. 3,,a spacing fabric 0 extends between'two adjacent plies and is united to each of the plies which it serves to space from each other. In the structure of Fig. 4 there is shown a relatively thin film w joined to a much thicker film l2, the thinner film being the one that is in direct contact with the lesion when the article is in use. Because this film i0 is relatively very thin, it makes possible diiiusion at a satisfactory rate of medicant from film l2 to the lesion. The cement 6 serves also as a spacing layer.
In the figures, the thicknesses are somewhat exaggerated in relation to other dimensions. The various film members that have been described as well as the cementing layer 6 must, be hydrophilic and, therefore, adapted to promote the diifusion of water and aqueous solutions of the medicants through the article. These films may be constituted largely or entirely of plastics that are hydrophilic and slowly soitenable by and ultimately soluble in water'as, for example, methyl. cellulose (of which a suitable grade is Methocel), polymerized vinyl alcoholoi plastic consistency, and a cellulose derivative such as an ether of cellulose and glycolic acid or a slowly soluble salt of it. The term hydrophilic" as applied to the films or base materials is used to mean that the films permit the ready diffusion of aqueous liquid therein.
In addition to the base materials of hydrophilic nature, the films include also the selected medicating material. chemically incompatible ones being separated from each other by the film forming material extending between the major proportions at least of such incompatible substances. Suitably the incompatible substances are disposed separately in the several films. Thus, a germicide containing available chlorine is contained in one of the individual films shown in the drawing and a germicide or local the relationship of any two of the films to eachother being as illustrated in the drawing.
The cementing material used may be simply portions of the film forming materials adhered to each other, say surface portions that have been initially softened by vaporized solvent and then pressed together. Or the cementing material may be some other hydrophilic, readily water 'penetrable cement such as a very thinfilm of any one of the film forming materials applied initially in a. suitable volatile solvent for such material, solvents for the film forming base materials disclosed being water, alcohol. acetone,
, or methanol, the organic solvents used contain ing some water.- A solution of '15 parts of water. I and 25 parts of alcohol is a particularly convenlent solvent for the cellulose ether. 1% use the word solvent to include any volatile liquid which may serve as a true solvent or as a medium for a dispersion. Wherever we use the word soluassaeat amples of which are sulfanilamide itself, sulfathiasole, and sulfapyridine. The asochloramide' destroys anti -sulfanilamide bodies known to be present in infected wounds. Before use. the alcchloramide and the sulfanilamide compounds, known to be mutually destructive, are kept isolated in separate films .of the composite article. Preferably the asochloramide is contained in the one of the films that is applied directly over the lesion when the article is in use. The asochloramidesodisposedreachestbetistue ofthe lesion first and prepares the site for the sulfa I drug. In this way the full activity of the sulfanilamide compound is preserved. It will be noted that the chemicals are extracted in their original form, that is, without losing their chemical identitles.
In general, the films are used in substantially drycondition. that is, of moisture content approximating that in equilibrium with the air or below that which causes development of objec- 'tlonable tackiness of the films. Also, the base tion, we include true solutions, colloidal solutions, and dispersions.
The films are cast in a manner suitable for the casting of films of plastic materials. Thus there is made a dope containing the desired film forming material, the selected medicating substance or compatible substances, and-a solvent for the base material and preferably also for the medicating material present. Thus, there may be used a solvent of the kind mentioned above in connection with the formation of the cement. The dope so formed and of concentration to give to it a freely flowing to syrupy consistency is cast upon plate glassor other smooth surface, the solvent evaporated, and the remaining film stripped from the casting surface and dried. The film is then plied with another film similarly made," for instance, containing a dififerent medicinal that is incompatible with that in the first film. Films made as, described are non-porous but water penetrable. c
When the spacing cloth is used, the preformed films may be pressed against the cloth sufficiently 0 contains medicant, is spread upon one side of the cloth and a like solution of the incompatible medicant is coated upon the other side in manner that is usual in the coating of bothsides of fabrics with such compositions as pyroxylin solutions.
When the films are preformed before assembly.
- they may be made of predetermined desiredthickness. When they are formed by spreading upon the fabric member and then evaporating the volatile solvent present, the film first formed is suitably made relatively thick. After such impregnation then the second film is applied as a rela-,
tively thin layer over one side of. the impregnated cloth, this thinner film being applied directly over s moist lesion when the ,article is in use.
The structure of the present invention is particularly useful in applying medication with azomaterial of the films is preferably non-metabolizable by microorganisms.
The invention will be further illustrated by detailed description in connection with specific examples of the practice of the invention.
,. Example 1 A homogeneous paste is prepared from the following materials: 27 parts Methocel, of viscosity 100 centipoises (cps.), 5.6 parts glycerin, 3.75 parts sulfanilamide, 250 parts water and 250 parts ethyl alcohol. This paste is applied to gauze using standard fabric coating equipment and the solvents removed by evaporation. The paste is applied in amounts sufficient to result in a weight of film of 1.5 to 2.0 ounces per square yard exclusive of the weight of the fabric.
A second homogeneous paste is prepared from 40 parts of Methocel, 100 cps., 10 parts triacetin, 1 part Azochloramide' (N,N'-dichloroazodicarbonamidine) and 500 parts of water. The above coated fabric is treated in a similar manner with the second paste at a rate sufiicient to result in the film weighing 0.2 to 0.3 ounce per square yard exclusive of the weight of fabric and sulfanilamide containing coating. The finished material is cut into the desired widths and used as a therapeutic film.
f Example 2 Sixty parts of polyvinyl alcohol (type B, medium viscosity), 12 parts glycerin, 8 parts sulfanilamide, 300 parts water and 400 parts ethyl alcoholare mixedto a homogeneous solution. This solution is poured into drying trays in thin layers and the solvent caused to'evaporate by the application of heat or exposure to dried air. To this dried film there is'added' a thin layer of a solution made from 30'parts Methocel, 4000 cps., 1 part Azochloramide, 10 parts triacetin, 300 parts water and 270 parts acetone. The solvents are removed by evaporation as before and the double layered film is stripped from the drying tray and cut .into
the desired size. Bufilcient liquid is poured into the trays to'give the sulfanilamide containing layer a weight of 2 ounces per square yard and the Azochloramide layer a weight of 0.2 to 0.3
ounce per square yard. This therapeutic film is normally used with the Azochloramide containing layer adjacent to the wound surface.
Example 3 A homogeneous paste made from 30 parts of polyvinyl alcohol (type 3 medium viscosity), 6 parts glycerin, 4 parts sulfadiazine, 150 parts ethyl alcohol, and 200 parts water is applied to Cellophane in a manner described in Example 1, at such a rate. that the dried film will have a weight of 1.5 to 1.8 ounce per square yard, exclusive of the weight of the Cellophane backer.
A second layer weighing 0.2 to 0.3 ounce per square yard after drying, is applied directly over the first layer. The paste used in the second layer is made from 25 parts of Methocel, 8 parts Azochloramide, 12 parts triacetin, 200 parts ethyl acetate and 250 parts acetone.
Example 4 parts of Methocel, 100 cps., 6 parts glycerine, 6 parts sulfathiazole, 200 parts methyl alcohol and 300 arts water are worked up into a homogeneous paste. This is applied to surgical gauze in a man-' ner described in Example 1, at the rate of 2.0 ounces per square yard.
A thin coating amounting to approximately 0.1 ounce per square yard is applied over this first coating. This second layer consists oi! unplasticized Methocel and is obtained by coating the previous material with a thin solution 01 Methocel in methyl alcohol. It provides a neutral separating layer.
A third layer is applied at such a rate so as to result in a layer weighing 0.2 to 0.4 ounce per square yard. The material used inpreparing this third layer consists of a homogeneous thin v paste composed of 50 parts Methocel 15 cps., 5
parts triacetin, 1 part succinchloramide, and 300 parts water.
Example 5 Films weighing 1.5 to 2.5 ounces to the square yard may be made, as described in any of the above numbered examples from a composition including an alkaline buffer in conjunction with a germicidal sulfanilamide compound, the buffer establishing the pH when the film is in use at a pH of about 8 to 10, at which pH the sulfanilamide The compositions applied are in solution in a mixture of alcohol and water, the non-volatile materials being as follows:
(1) '75 parts Methocel, 15 cps., 10 parts sulfanilamide, l0 parts'glycerin, 1 part calcium carbonate, and 0.2 part sodium carbonate.
(2) 75 parts Methocel, 100 cps., 8 parts su1fa-' thiazole, 10 parts glycerine, and 1.5 parts secondary sodium phosphate.
(3) 75 parts polyvinyl alcohol, 5 parts sulfadiazine, 15 parts glycerin, 0.2 part sodium carbonate, 1.0 part sodium bicarbonate and 1.0 part calcium carbonate.
(4) 60 parts Methocel, 4,000 cps., 10 parts sulfanilamide, 10 parts triacetin, 1 part calcium carbonate, 0.8 part borax, and 0.2 part boric acid.
It will 'be understood that films made as described are preferably sterilized before use, as, for example, by autoclaving with steam for a short period of time.
Certain subject matter herein disclosed but not claimed is covered in our copending application Ser. No. 456,458, flled on August 26, 1942, and enmum Sulfanilamide film.
It will be understood also that it is intended to coverall changes and modifications oi the ex-- A dressing for a liquid exuding lesion which comprises a plurality of plies, at least one of which is thin, of pliable, hydrophilic', non-porous but water penetrable material in fllm form, azochloramide distributed throughout the one of the said plies that is thin and that is to be in contact with the lesion when the dressing is in use, and a bacteriostatic sulianilamide compound distributed throughout another of said plies, so that the azochloramide is extracted and reaches the lesion first after application of the dressing to the lesion and prepares the site for the sulfanilamide compound in advance of contact of the sulfanilamide compound with the lesion.
FRANZ c. s. FREDERIKZ .1. n: narrow.