This application discloses subject matter related to our copending U.S. patent application Ser. Nos. 08/838,078 and 08/839,614 both filed Apr. 14, 1997, to patent application Ser. No. 08/946,364 filed Oct. 7, 1997 and to patent application Ser. No. 09/037,160 filed Mar. 9, 1998, to a patent application Ser. No. 09/302,726 filed Apr. 30, 1999 and entitled xe2x80x9cGAS-DRIVEN SPRAYING OF MIXED SEALANT AGENTSxe2x80x9d all naming Gordon H. Epstein as first inventor, and to an international PCT patent application in the name of the assignee of all interest of the instant application, Biosurgical Corporation, Application No. PCT/US99/09663 also entitled xe2x80x9cGAS-DRIVEN SPRAYING OF MIXED SEALANT AGENTSxe2x80x9d. The disclosures of the aforementioned United States patent applications, and one international PCT patent application, xe2x80x9cthe related applicationsxe2x80x9d, are hereby incorporated herein by reference thereto. Continuation status is not claimed.
(Not applicable.)
1. Field of the Invention
The present invention relates to an applicator and method for spray application of a non-Newtonian fluid to a work surface. The invention is particularly, although not exclusively, useful for applying tissue sealant agents containing a polymer such, for example, as fibrinogen, to biological tissue to effect hemostasis or achieve other therapeutic results. More particularly, it relates to spray application of tissue sealants from a hand-held applicator.
2. Description of Related Art Including Information Disclosed under 37 CFR 1.97 and 37 CFR 1.98
Use of tissue sealants and other biological materials is an important emerging surgical technique, well adapted for the operating room or field environments such as the doctor""s office or mobile medical units. Preferred sealants include fibrin sealants which are formed from blood plasma components and comprise, on the one hand, a first agent containing fibrinogen and Factor XIII and on the other hand a second agent which usually includes thrombin, and calcium ions. The fibrinogen is capable of a polymerizing and being cross-linked to form a solid fibrin clot when the agents are mixed. The necessary additional factors to simulate relevant portions of the natural blood coagulation cascade are suitably distributed between the fibrinogen and thrombin agents.
High levels of protection against transmission of infections or induction of immunological reactions can be assured by using an autologous or single-donor source for both agents. Such sealants are highly effective, are biologically degraded without residue and may promote wound healing.
They may be dispensed from hand-held applicators which can generally be classified as droplet applicators or spray applicators. Droplet applicators dispense a continuous stream or single line of droplets from a cannula, or other dispensing tube. Spray applicators generate one or more patterns of atomized fluid that can be applied to a work surface so as to cover a wider area than the output from droplet applicators. In many cases the applicators comprise dual syringes providing reservoirs for two sealant agents which are dispensed by manually operated plungers which drive the fluids out of the reservoirs to be mixed internally or externally. Some examples of such applicators, especially ones that address the problems of mixing sealant agents internally, are disclosed in the related applications.
Capozzi et al. U.S. Pat. No. 5,116,315 discloses a spray applicator that outputs a mixture of two sealant agents which applicator is provided with replaceable spray orifices so that when they become clogged with sealant, the user can remove the clogged orifice and replace it with a new one. Changing the clogged orifices is inconvenient and may be difficult and inconvenient during surgery. Fibrin sealants can coagulate very quickly, in a matter of seconds. Accordingly, such a spray applicator can easily become clogged between applications if it is set down for a minute or two. The need to change the spray orifices during a surgical procedure, and to have replacement orifices available, may be quite disruptive or impractical.
Furthermore, the momentum of the spray droplets leaving the applicator is derived from manually applied pressure to the sprayed liquid. Naturally, the pressure with which the liquid is applied to the spray orifice, and therefore the momentum with which the droplets are discharged from the spray orifice, is subject to variation, caused by the mechanics of the dispensing mechanism or simple inability of a human operator to apply constant pressure throughout a range of manual movement. Accordingly with the Capozzi spray applicators, it is difficult to produce an even spray having a consistent spray pattern. It is also difficult to discharge the droplets from the applicator with a constant momentum, as would be desirable for consistent application of materials such as a surgical sealant.
Another approach to this problem has been to entrain the individual sealant agents in separate gas streams, providing overlapping spray patterns, with the intention that the agents will mix in the air or on the tissue surface. Thus, for example, Redl U.S. Pat. No. 4,359,049 discloses a dual syringe tissue adhesive applicator for dispensing two adhesive agents, which applicator employs a disposable mixing needle to provide a mixed sealant output a in the form of a liquid stream or a series of droplets. To provide a spray output, FIGS. 4 and 5 of Redl disclose the use of two pressurized gas streams emerging from outlets 50,51 in the region of the valves 43,44 of conveying channels 41,40 which separately supply adhesive agents from syringe bodies 1 and 2. (See column 3, lines 45-47.) Two spray patterns are generated and, according to Redl xe2x80x9cunite at a distance of about 10 to 20 cm, rapidly forming a thin uniform adhesive film on the surface to be adhered or sealed.xe2x80x9d, see column 4 lines 1-3. As taught in the related application filed Apr. 30, 1999 application Ser. No. 09/302,726, such external mixing of separate sprays provides ineffective mixing and the resultant sealant may lack adhesive or cohesive strength.
Furthermore, depending upon the potency of the particular formulations employed, coagulation of the sealant may take place very rapidly, once the necessary sealant agents are mixed, yielding a gel within perhaps 5 or 20 seconds of mixing. Though often desirable for surgical reasons, such fast-acting properties may aggravate difficulties with atomization, when a mixed sealant is sprayed, and can lead to fouling or clogging of the spray applicator.
Surprisingly, we have found that many known spray applicators exhibit poor spray quality when applying fibrinogen, even spray applicators specifically intended for fibrinogen application, such as those referenced above. Studies we have conducted, pursuant to the present invention, have shown that a fibrinogen agent tends to stream instead of spray when dispensed through conventional spray applicator nozzles, which is wasteful and ineffective. Such drawbacks may render the applicator quite unsuitable for surgical use. The possibility of such streaming is particularly unsatisfactory for many surgical applications where a thin film of sealant is desired. In some cases, thick layers of sealant can be a barrier to the blood supply of connected tissues. To meet the need for a thin layer of deposited sealant, it is desirable for a spray applicator to be capable of generating a consistent, fine spray.
Pursuant to our studies, it appears that because the fibrinogen agent is a polymer solution containing a dissolved long-chain polymer, the fibrinogen molecule, a molecule which has a molecular weight of about 400,000 daltons, the fluid characteristics of the fibrinogen agent may be non-Newtonian. Thus, the viscosity of the fibrinogen agent fluid may vary with shear rate. In particular, the elongational viscosity, which is the resistance of the fluid to being stretched or drawn, increases as the elongational strain rate increases. Consequently, the liquid resists normal atomization forces that are effective to extrude conventional Newtonian fluids, for example water, into thin columns which can quickly break up into a desired fine mist of droplets. Such non-Newtonian properties of fibrinogen solutions or dispersions, attributable to the polymeric character of fibrinogen, renders their behavior unpredictable when subjected to atomizing or nebulizing forces, and may explain why fibrinogen sealants can be difficult to spray.
As taught by Walters in Rheometry (Chapman and Hall Ltd., 1975) at page 25, some non-Newtonian liquids including suspensions of starch, and polymer solutions, exhibit shear-thickening behavior, wherein the viscosity increases with shear rate.
Such systems can display startling phenomena not found in conventional Newtonian liquids. One such phenomenon is the Weissenberg rod-climbing effect wherein certain non-Newtonian liquids subjected to mixing with a rod, may climb up the mixing rod. Lodge in Elastic Liquids, An Introductory Vector Treatment of Finite-strain Polymer Rheology, (Academic Press, 1964) describes, at page 242, a die-swell effect where a non-Newtonian extruded through a die may increase in diameter as it leaves the die. Pursuant to the invention disclosed herein, it is apparent that both effects may be of interest to the problem of spraying a sealant comprising a mixture of fibrinogen and an activator such as thrombin, because of the non-Newtonian nature of the fibrinogen component. Since the sealant agents comprising the mixture must be both mixed and sprayed both the rod-climbing and die-swell phenomena may manifest themselves, to hinder the process.
A still further problem arises from an observation reported by Lodge, that atomization of polymer solutions is particularly difficult because they form unusually stable liquid jets, which may extend a considerable distance from the nozzle before surface tension effects cause the jets to break up into separate drops.
Whereas many mathematically derived analytic solutions are available for predicting the fluid behavior of conventional Newtonian fluids, for example water and aqueous solutions of small molecule substances, for polymer solutions, few analytical solutions exist. Henry Green, in Industrial Rheology and Rheological Structures (John Wiley and Sons, Inc., 1949) notes that empirical solutions are the only recourse and teaches that when no yield value for an applied stress exists, and the molecules align on flow, then neither Newtonian nor Bingham concepts can be developed into satisfactory instrumental equations. No fundamental concept exists that will define such a material rheologically and lead to a valid instrumental equation of flow. Accordingly, theoretical considerations may explain why there is difficulty in spraying a non-Newtonian fluid, but a offer no help in solving the problem.
Our related patent application filed Apr. 30, 1999 Ser. No. 09/302,726 disclosed and claimed delivery of at least two sealant agents to a gas stream to generate a spray containing the at least two sealant agents but did not address the problems of spraying non-Newtonian fluids. There is accordingly a need for a spray applicator, and method of spraying that will generate a good spray with non-Newtonian fluids such as polymer solutions, and especially with a fibrinogen agent.
The present invention solves the problem of providing a spray applicator, and method of spraying that are effective with liquids that are difficult to spray, for example non-Newtonian fluids, such as polymer solutions, especially an aqueous fibrinogen agent.
To solve this problem, the invention provides, in one aspect, a spray applicator having a spray nozzle comprising:
a) a liquid-dispensing aperture providing a source of a liquid to be sprayed;
b) a spray plate disposed to be impacted by liquid dispensed from the dispensing aperture; and
c) a gas nozzle to provide a stream of carrier gas;
wherein the carrier gas stream can carry dispensed liquid away from the spray plate to form a spray.
The liquid can be manually dispensed from the dispensing applicator as a jet or stream and wherein the spray plate has an impact surface disposed to intercept the jet or stream. Preferably, the spray plate acts to thin the dispensed liquid and has a shear edge, the carrier gas stream drawing dispensed liquid away from the shear edge.
The spray applicator according to the invention is surprisingly effective in generating a high-quality, fine spray even when the liquid is a non-Newtonian liquid. While the invention is not limited by any particular theory, it appears that the spray plate is effective in converting kinetic energy of the dispensed liquid into a dispersing force and that this dispersing action is augmented by thinning of the liquid on the spray plate and shearing at the shear edge.
In preferred embodiments, the liquid can be an aqueous polymer solution, for example a coagulable sealant, such as a fibrinogen sealant agent, or a mixture of a fibrinogen agent and a thrombin agent.
Optionally, the applicator comprises a suction-applying member extending distally of the spray nozzle and wherein the spray is discharged from the spray nozzle in the direction of the suction-applying member. The suction applying member can prepare the work surface, for example surgical tissue for the application of a sprayed sealant. Also, a preferred embodiment of spray applicator comprises a fibrinogen agent reservoir, a thrombin agent reservoir, a manual actuator to drive the agents from the reservoirs, a dispensing cannula terminating in the liquid dispensing aperture, a mixing chamber to mix the agents and deliver the mixed agents to the dispensing cannula, a suction source and a suction clearing device to apply suction to the mixing chamber and dispensing cannula to clear residual material therefrom.
In another aspect, the invention provides a method of spraying a non-Newtonian liquid comprising manually dispensing the liquid through a dispensing applicator as a jet or a stream, impacting the dispensed liquid on a spray plate and entraining the liquid impacting the spray plate into a gas stream to provide a spray.
Preferably, although not necessarily, the sealant is a biological sealant, for example a tissue adhesive, and the work surface is a biological tissue subject to surgery. The sealant agents can comprise a first, structural agent capable of gelling, and preferably of solidification and a second, activation agent which activates such gelling and, optionally, solidification. More preferably, the sealant is a tissue sealant and the first agent comprises fibrinogen and the second agent comprises, or can generate a fibrinogen activator, especially thrombin or an equivalent thereof.
USPTO Backgrounds
USPTO Backgrounds