US 2507244 A
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Patented May 9, 1950 SURGICAL GELATIN DUSTIN G POWDER AND PROCESS FOR PREPARING SAME John T. Correll, Kalamazoo, Mich., assignor to The Upjohn Company, Kalamazoo, Mich., a corporation of Michigan No Drawing. Application April 14, 1947, Serial No. 741,419
Claims. (Cl. 260-117) This invention relates to a powder, suitable for surgical use, which is absorbable by the bodies of living animals.
The technique of surgery, as developed through years of experience, requires the surgeon, after having thoroughly disinfected his hands, to wear rubber gloves during the actual manipulative performance. These rubber or surgical gloves are of a special construction, which is necessary according to the nature of their use. To allow snug fitting of the hand, the gloves must be extremely thin. This thinness, however, is disadvantageous in that it renders the gloves weak from a mechanical standpoint so that they are not capable of withstanding extensive pulling or stretching. To obviate tearing while they are in the process of being put on just before surgery, experience has shown that the gloves must be lubricated.
The most common lubricant for this use, until the present invention, has been a special sterile powdered inorganic talc. This talc, which is water-soluble and, by the nature of its physical structure, lubricating, allows the tight-fitting gloves to be fitted to the hand, and removed therefrom, without their rupture, and is therefore satisfactory for the surgeons immediate purpose, viz, donning the gloves Without their rupture or contamination. However, this talc is not entirely satisfactory from the standpoint of ulterior physiological effects upon the patient being treated.
It is well known that inert substances, foreign in composition to the body, exert a deleterious effect when allowed to remain in contact with the healing surfaces of an incision. This reaction, called a foreign-body reaction, instigates a permanent and progressive inflammation which may cause many complications, such as adhesions. Inert foreign bodies in the incision may also cause granulomatous lesions of the peritoneum, draining sinuses, scar nodules, and malfunctioning intestinal stomas.
It has been shown (Seelig, Verda, and Kidd, Jour. Am. Med. Assoc. 123, 950, 1943; Seelig, The Surgical Clinics of No. Am., Oct. 1944, Barnard Hospital Number; Seelig and Verda, Jour. Mount Sinai Hospital XII N0. 1, May-June 1945; Seelig, Jour. So. Med. Assoc. 38, 4'70, 1945; Lichtman, McDonald, Dixon, and Mann, Surg. Gync. and Obst. 83, 531, 1946; Antopol, Arch. Path. 16, 326, 1933; Erb, Surg. Gym. and. Obst. 60, 40, 1935) that the talc commonly used in surgical procedures acts as a foreign body, with the above-mentioned undesirable results. The need for a lubricant which can be used in the same manner as talc, but
which does not have the attendant undesirable properties of talc, has been recognized in the references already given. These references further show that various attempts to solve this problem have been made, but no success is indicated.
It is, therefore, an object of the present invention to provide a powder which is suitable for use as a lubricant of such surgical devices as rubber gloves, but which, being absorbable by the body fluids, does not effect complications which arise from the employment of an inert material. As the new powder is water-insoluble, it is neither dissolved by perspiration nor made tacky or sticky by exposure thereto. The product of this invention is a water-insoluble, sterile, non-toxic, non-antigenic, non-tissue irritating hardened gelatin powder which is absorbable by the animal body without residue or untoward side reactions, and which is capable of safe and satisfactory lubrication of rubber articles such as the aforementioned surgical gloves.
The proteolytically digestible powder of the invention is prepared by suitably hardening a gelatin, either before or after reduction to a powder. A gelatin solution may first be hardened either by the use of a chemical hardening agent, such as an aldehyde, or by heat, and thereafter subjected in either flake, slab, or powder form, to the synergistic action of a high-temperature treatment. Gelatin flake may be suitably hardened by merely heating the same, in its flake form or after further reduction to a powder, at a temperature above about 145 degrees centigrade for a period of time between about 20 and about hours.
The degree to which the gelatin is changed or hardened is of critical importance, for, if the change from the original gelatin is not sufficient, the resulting product will be water-soluble or partially water-soluble and the powder will lose a certain proportion of its lubricating properties when exposed to moisture. On the other hand, if the change or hardening be carried too far, the product will no longer be susceptible to proteolytie disintegration and absorption by the body fluids, and thus, not being absorbable by the body, will cause the formation of granulomas and adhesions in the same manner as any other foreign substance. Accordingly, to determine whether the product has been suitably hardened, it should be found to be water-insoluble and proteolytically digestible. The digestion time may be determined in a manner similar to that employed for determining the proteolytic absorbability of cat gut sutures, such as, for example, by exposure to either a 5.0 or 0.5 per cent pepsin solution, in which case proteolytic digestibility is usually satisfactory if complete within a period of about one-half hour and about six hours, respectively, for the two concentrations given. Beyond these limits, the product may. be unsuited. for the pre.-. scribed use.
The powder should not comprise any ingredients of an antigenic nature, but, while pure gelae tin with or without a minor; proportion. of aldehydic hardening agent is presentlynzonsidered' the; most satisfactory composition, other non-antigenic, sterile ingredients may beaddedjfi' l chi addition is considered desirable;
The hardening agent, if such is employed, may be of any suitable type, formaldehyde bein Dre, ferred. This aldehydic hardening agent may be; present in an amount not to exceed about three per cent by weight in the powdered product. Any other method of hardening a gelatin solution may be'employed, p ioy dedbnly thatthe, de.- sired water-insoluble., non-antigenic, vproteolytically-digestible powder be: produced: thereby; Circulation of air having :a: relative i humidity of: ten per centror. less ata; temperature; between aboutaZOrrand about135. de rees: centigrade, most desirably. at: about;.3.0 degrees centigrade'his' a. satisfactory. method ,of' drying partially-solidified, gelatin slabs, but spray-dryingbefore gelation of. the solution i is..complete-.may; be employedrif dc;- sired, and insome instances: is.:preferred.
While the. starting; material .folithepreparation of; the new gelatin; powder; maycomprise. either;- a gelatin'solutlon or gelatinfiake, fillilWhilQfihBf particular. starting, material may-be dried anct'.
hardened in any suitable manner, the-synergistic; effects of drying at-relatively higher temperatures as astep forthe attainment of-the proper 'physia cal properties is requisite. 'Ihis step; comprises: subjecting the. dry gelatin .flake or powder, to .a'. relatively high temperature above about Hide:- greescentigrade, for a;,relatively,len thy-period of time, e;g., fromaboutf20 to lyhours,.,preerly at 1 a temperaturebBtWeengabput ;1,62.:and; 191;. degrees .centigrade; (32.0; to 3f75 degrees Fahr en.-- heit) This treatmentzhas been found. to; pro
duce the. mostsuitably hardenedzor; denatured: gelatin powder; when; used: alone; or in. combine: tion with other steps. A combination. oi; the: formaldehyde treatment and: this heat denatur ing is .avery practioalmarmer of :producingthei product offthe presentinvention. The: finely" ivideo". gelatinpowder, whendesired to be. used:
as a lubricant for. rubber articles demandingsterility, should of course be sterilized, and such. isusually. accomplishedaby. heatin at ,elevated temperatures as-.illustrated in theexamples;
The following. examplesare given to-illustrate: the preparation of the-product ofthise-invention, but are in .no. way to be construed'as-limiting.
Example 1 One kilogram t :skimgelatin fiake is dissolved; in liters of warm water to make a 10-;per-centv gelatin solution. The solution .iscooled to -about 40 degrees centigrade and 10 milliliters-got-U. S,.-.P-.-'. 40 per. centformaldehydesolution is addedwith stirring. The solution isallowedto stand-at room temperature until a stiff gel;forins whereafter;
the jelly is cut into ;slabs,;of suitable size, preferablyless than oneinch thick, and-dried by; circu: lation of air -of;-l0 per; cent or:-less relativeqhumideity at a temperaturegof abeut,30degreesrcenti rad The; dried. hardened; elatin flakes.- are--.
at a temperature of about 145 degrees centigrade for between 15 and hours. This powder is finely pulverized and bolted to the desired particle size, less than 50 microns in diameter. After packaging in a. suitable container, the powder is sterilized. by heating in; dry air at degrees centigrade for four hours. The powdered product is biologically absorbable and causes no foreign body reaction in surgical use.
Example 2 powder-was then further pulverized and bolted= to the desired size, preferably 50 microns or less' in diameter, and packaged in suitable containers and sterilized, e;g., by heating in dry air to a temperature of 145' degreescentigrade fora period of" about four hours. The powder is suitably biologically absorbable and non-irritating 7 to incised human tissue.
Various modifications maybe made in the in-- vention without departing from thespiritor scope thereof; and it'is' to-be" understood that I- limit myself only as defined intheappended claims.
1. A sterile, substantially; water-insoluble, nonantigenic, completely proteolytically digestible powder suitable forsurgical lubrication consisting essentially of gelatin that has been hardened to the-stage of substantial wa-ter-insolubility' and that has'thereafter been pulverized and subjected to heat treatment, whichpowderedmateria'l'is completely digestible within approximately 0.5
hour in 21' 5 percent' and within-approximately6- hours in-a 0 .5 percent-aqueous pepsin solution.-
2; A sterile, substantially water-insoluble, nonantigenic, completely proteolytically digestible:- powder suitable for-surgical lubrication consistingessentially-of gelatin that has been hardenedby" treatment withlessthan approximately 3 percent by weight of formaldehyde in aqueous solution, thereafterdried'and pulverized and'subjected-to heat treatment until theproductis no' longersubstantially-soluble in water but still is scempletely digestible within approximately 0.5- hour: in a E'percent and-Within approximately 6' lio-ursina 0.5 percentaqueous solution of pepsin;
3". A-sterilepowder suitable for surgical lubri-- cation as-defined-inelaim Zand further charac terizeddn thatthe. individual particles thereof are of size: less than approximately 50 microns in diameter.
4: A pr sees-for the production of asubstantially water-insoluble; non-antigenic, completely proteolyticallydigestible powder suitable for sur-- gical" lubrication: which comprises: hardening" gelatin to a-state'of substantial water-insolubility andithereafter heating saidproductat a tem peraturebetween approximatelylS degrees and ;.approximately 191' degreescentigrade for" such period. that ,the product is :substantially waterinsolubler but still is completely: proteolyticallydigestible '1 5;- .A'. procession-the; production :of a-substamtheneround; toc ifine; powder. which-.-is;heated ugtiallyzwater=ins0lub1e;..n0n-1antigenic,: completely- REFERENCES crrnn The following references are of record in the file of this patent:
UNITED STATES PATENTS Number Name Date 658,747 Altschul Oct. 2, 1900 659,204 Brat Oct. 9, 1900 1,021,674 Horowitz Mar. 26, 1912 FOREIGN PATENTS Number Country Date 555,718 Germany July 27, 1932 Certificate of Correction Patent No. 2,507,244 May 9 1950: i 'f JOHN T. CORRELL It is hereby certified that error appears in the printed specification of the above numhered patent requiring correction as follows:
Column 1, line 22, for the hyphenated Word Water-soluble read water-insoluble THOMAS F. MURPHY,
Assistant Commissioner of Patents.