CA1319871C

CA1319871C - Composite medical article including a medicinal substance onlay and methods for preparing the same

Info

Publication number: CA1319871C
Application number: CA000510358A
Authority: CA
Inventors: Philip N. Sawyer
Original assignee: Interface Biomedical Laboratories Corp
Current assignee: Interface Biomedical Laboratories Corp
Priority date: 1984-06-28
Filing date: 1986-05-29
Publication date: 1993-07-06
Anticipated expiration: 2010-07-06
Also published as: US4606910A

Abstract

ABSTRACT

COMPOSITE MEDICAL ARTICLE INCLUDING A MEDICINAL
SUBSTANCE ONLAY AND METHODS FOR PREPARING THE SAME

An improved composite medical article is made by fusing an onlay of a medicinal substance (27) to a porous body (28) which is already impregnated with the same or with a different medicinal substance. The medicinal substance may be a hemostatic agent comprising a collagen or collagen-like substance which has been modified by rendering the surface charge thereof effectively more positive than prior to modification.

Description

FIELD OF THE INVENTION

This invention relates to composite hemostatic articles and to methods of preparing the same.

BACKGROUND

In various prior patents, I have shown how certain modifications of collagen, collagen-like compounds and gelatin could augment the hemostatic properties of such compounds by manipulation of the surface charge and microstructure thereof.
In U.S. Patent 4,238,480, I disclosed that an improved hemostatic agent could be made by treating collagen or collagen-like substance to render the surface charge effectively more positive and that the thusly modified substance could be employed to control or terminate bleeding.

Other references relate to the provision of liquid absorbent patches, pads or the like to carry medicinal substances. For example, in U.S. Patent 4,022,203, Ackley discloses a liquid absorbable pad means containing a quantity of blood coagulating substance to reduce blood flow. In U.S.
Patents Nos. 4,390,519 and 4,404,970, I disclosed that a modified blood-soluble hemostatic agent could be combined with or incorporated into a porous or supporting body such as, for example, a gauze pad, a bandage, a laparotomy pad or sponge. By enbodying the improved hemostatic agent into such porous body, the resulting article itself becomes a hemostatic material possessing the properties of the agent and may be applied to an area of trauma or injury where such properties may be utilized.
I have discovered that there are certain additional advantages which result from the use of a composite medical article if an onlay of a medicinal substance can be fused to the face of an article which has already been impregnated with the same or a different substance so that the onlay is the first to come is contact with an area of trauma or injury.

SUMMARY OF THE INVENTION
_ _ The provision of a coating of a medicinal substance on a porous body which is already impregnated with the same or a different medicinal substance will have a number of advantages in clinical application over the composite medical articles known previously. The different porous materials in which medicinal substances may be incorporated -- gauze, sponge, tissue, etc. --have different absorbencies and different effects on the healing rate of a wound to which the materials may be applied. The provision of a coating of a medicinal substance which absorbs serum and plasma from an injured area on the surface of such materials will make the effects produced by use of the differing materials more uniform by mitigating any problems which may be encountered in dealing with a particular substrate in clinical use. In addition, if the coated medicinal substance is more absorbent of serum and plasma from an injured area than is the material which it coats, the provision of such coating has been found to relieve pain in a patient more rapidly than will the material without such coating. For example, a hemostatic agent as disclosed in my U.S. Patent 4,238,480 will have this effect.
Further, the provision of a layer of medicinal substance as a coat on the surface of a medical article can have a comfort effect on a patient by acting as a cushion between the wound and the article. By medical substance, what we mean is any agent having a therapeutic effect on cuts, burns, wounds, trauma, injuries and the like. These substances include both hemostatic agents, which are prepared by modifying a collagen or a collagen-like substance by dissolving it in water and then rendering the surface charge effectively more positive than prior to the modification while retaining the water solubility of the substance, generally in accordance with U.S. Patent No.
4,238,480.

It is an object of the invention to provide an improved composite medical article.

It is another object of the invention to provide an improved method for preparing such composite medical articles.

To achieve the above and other objects of the invention, there is provided a method comprising incorporating a first medical substance into a porous body to saturate the body with said substance, preparing a second medicinal substance with at least a portion thereof in liquid phase, affixing an onlay of said second medicinal substance to said saturated body so as to form an onlaid composite medical article, and drying the article.

According to one specific embodiment of the invention, the first and second medicinal substances may be of the same or substantially the same chemical composition. One or both may preferably be a hemostatic agent prepared by modifying either a collagen or a collagen-like substance in water and modifying the thusly dissolved substance to render the surface charge thereof effectively more positive than prior to modification while retaining the water solubility thereof.
According to a feature of the invention, the medicinal material is prepared by freezing the first medicinal substance in the porous body. The porous body may preferably be saturated with said first medicinal substance prior to said freezing step.
According to a preferred embodiment of the invention, the second medicinal substance is prepared with at least a portion thereof in liquid phase by first freezing said second hemostatic agent and then melting at least the surface of the thusly frozen second medicinal substance.

BRIEF DESCRIPTION OF THE DRAWINGS

Figs. 1-6 are schematic representations of a sequence of operations illustrating a method of the invention.

Fig. 7 is a diagrammatic view of an apparatus for use with the invention.

Fig. 8 is a diagrammatic view of another apparatus for use with the invention.

DETAILED DESCRIPTION

With reference to Fig. 1, a medicinal substance 2 is placed in a vessel 4 in liquid phase. In accordance with a preferred embodiment of the invention, the medicinal substance is a hemostatic agent and may comprise a collagen substance or a collagen-like substance which has been modified by dissolving the substance in water and modifying the thusly dissolved substance to render the surface charge thereof effectively more positive than prioi- to modification, in manners which are shown, for example, in our earlier Patent No. 4,238,430. Such modified collagen or collagen-like substance may be prepared as taught in said Patent 4,238,430 and may be freeze dried. The thusly modified and freeze dried hemostatic agent may be dissolved in water for use as the hemostatic agent(s) of the present invention.

As shown diagrammatically in Fig. 2, the hemostatic agent 2 in the vessel 4 may then be frozen into the solid phase.
Reference numeral 2' is used to designate the hemostatic agent in solid, as opposed to liquid, phase.

As shown in Fig. 3, a porous body 6 incorporating a medicinal substance such as a hemostatic agent 8 together form a hemostatic material 10 which is placed or prepared in a container 12. The hemostatic agent 8 may be of the same or of substantially the same chemical composition as the hemostatic agent 2 shown in Fig. 1. In other words, the hemostatic agent 8 may be prepared in accordance with the disclosure of, for example, U.S. Patent No. 4,238,480 by modifying a collagen or 131~871 collagen-like substance by dissolving it in water and rendering the surface charge thereof effectively more positive than prior to modification. Such hemostatic agent may be incorporated into a porous body such as, for example, a bandage, a small gauze sponge, a pad of surgical gauze, a laparotomy pad, a small sponge of natural or synthetic material or the like as shown, for example, in my earlier U.S. Patent No. 4,404,970. As shown in the said patent, the hemostatic agent 8 may be incorporated in the porous body by, for example, freezing and drying or vacuum drying the agent in the porous body.

Although lyophilization techniques are known, the following steps may be used relative to the above disclosure:

151. Dispense 50 ml amounts into plastic 100 mm petri dishes.

2. Shelf-freeze in lyophilizer (e.g.. Vitrus model 100 SRC-7) at minus 30 to minus 50 C. for 3 to 5 hours, or until eutectic point has been determined.

3. Set condenser for one to two hours; begin vacuum with no heat for three hours.

254. Set shelf heat to plus 30 C. and continue for 48 hours.

Gamma irradiation may be used for sterilization. The following may alternatively be used for sterilization:

301. Place in sterilization envelope and seal with indicator inside.

2. Gas sterilize with ethylene oxide through normal cycle.
(Alternatively gamma ray sterilization with Cobalt irradiation to 35greater than 20 megarads.) 3. Aerate thoroughly following exposure to ethylene oxide.

According to a preferred embodiment of the invention the porous body 6 will be saturated with medicinal substance 8 in liquid phase. The mixture of liquid medicinal substance 8 in porous body 6 may then be frozen as illustrated diagrammatically in Fig. 4.

Referring now to Fig. 5, the frozen material 10 with medicinal substance 8 incorporated thereinto is placed on top of frozen medicinal substance 2', in vessel 4. The surface of medicinal substance 2', is melted (melted portion designated by reference numeral 2) by methods will known in the art. The medicinal substance 2', is then fused to the material 10 by refreezing the melted portion 2 of medicinal substance 2' to material 10. The fused material-medicinal substance may then be freeze dried or vacuum dried to remove water from the resultant article. Fig. 6 shows a completed freeze-dried composite article wherein the medicinal substance 2 has been fused to the face of the material 10 and subsequently freeze dried or vacuum dried.
An apparatus for the application of an onlay of medicinal substance to a continuous strip of material in accordance with the principles of the invention will now be described. As shown in Fig. 7, the medicinal substance 2 can be applied in liquid form to a strip of material 28 by means, for example, of a spray applicator, indicated generally at reference numeral 20. Spray applicator 20 comprises a vat 22 containing medicinal substance 2 in liquid form. In a preferred embodiment of the invention, the medicinal substance is a hemostatic agent comprising from 0.25 to 1.5~ of an aqueous solution of a collagen or collagen-like substance which has been modified to render the surface charge of such substance effectively more positive than prior to modification in accordance with the teachings of U.S. Patent 4,238,480. The thickness of the onlay preferably is 2-3 mm. The agent 2 is discharged through nozzle 26 to deposit a layer of said agent 27 onto strip 28. Strip 28 comprises an already frozen, saturated mixture of hemostatic agent in, for example, a bandage. This preferably will be prepared in accordance with the teachings of U.S. Patent No. 4,390,519 or U.S. Patent No.
4,404,970. A continuous layer of agent 2 may be deposited onto strip 28 by moving the strip relative to nozzle 26. Valve 24 may be used for regulating the flow of hemostatic agent 2 through nozzle 26. A liquid layer of hemostatic agent 2 which is deposited on strip 28 may then be fused to said strip by passing said strip through a freezer dryer as indicated diagrammatically at 30.
An alternative apparatus for production of a continuous strip of a composite article such as a hemostatic article in accordance with the invention as shown in Fig. 8. A strip of hemostatic material 46 comprising a frozen, saturated mixture of a hemostatic agent in a bandage is passed by a rotating cold wheel 42. The wheel is rotated through a vessel 40 containing preferably 0.25 to 1.5% of an aqueous solution of hemostatic agent 2 which, for example, is prepared in accordance with the disclosure of U.S. Patent No. 4,238,480. The solution may alternatively comprise up to 10% of the agent 2. The wheel comprises a liquid absorbent surface 44 which is a sponge or felt material or the like. The sponge or felt material 44 of the surface picks up hemostatic agent from vessel 40 and brings it into contact with the surface of strip 46 where it is absorbed by the surface of the frozen material, as shown at 48. The strip of hemostatic material with an absorbed layer of hemostatic agent is then advanced into a thin mouth, small volume, high energy, freeze dryer as indicated diagrammatically at 50, to produce a composite bandage in a continuous strip. Cutting means, as indicated diagrammatically at 54, may also be supplied to cut the continuous strip into desired sizes.
There will now be obvious to those skilled in the art many modifications and variations of the above embodiments. These modifications and variations will not depart from the scope of the invention if defined by the following claims.

Claims

1. A method comprising incorporating a first medicinal substance into a porous body to for a medical material, preparing a second medicinal substance with at least a portion thereof in liquid phase, affixing an onlay of said second substance to said material by freezing the liquid portion of said second substance to said material whereby to form an onlaid medical article, and drying said article.

2. A method as claimed in Claim 1 wherein the first and second medicinal substances are substantially the same chemical composition.

3. A method as claimed in Claim 2 wherein the first and second medicinal substances are first and second hemostatic agents prepared by modifying one of the group consisting of a collagen or a collagen-like substance by dissolving the latter substance in water and modifying the thusly dissolved substance to render the surface charge thereof effectively more positive than prior to modification while retaining the water solubility of the collagen or collagen-like substance.

4. A method as claimed in Claim 3 wherein the second hemostatic agent is incorporated into said porous body in liquid phase and is subsequently frozen thereonto.

5. A method as claimed in Claim 3 wherein the medical material is prepared by freeze drying or vacuum drying the first hemostatic agent in said porous body.

6. A method as claimed in Claim 4 wherein the porous body is saturated with said first hemostatic agent.

7. A method as claimed in Claim 3 wherein the second hemostatic agent is prepared with at least a portion thereof in liquid phase by first freezing said second hemostatic agent and then melting at least the surface of the thusly frozen second agent.

8. A method as claimed in Claim 1 wherein the onlay of said second medicinal substance is affixed to said material by rotating a wheel applicator through a vessel containing said second substance and past said material respectively so that a quantity of said second substance is deposited first on said wheel applicator and subsequently on said material with at least a portion thereof in liquid phase, and freezing the liquid portion of said second substance to said material.

9. A method as claimed in Claim 8 wherein the liquid portion of said second substance is frozen to said material by passing said material with said second substance deposited thereon into a freezer.

10. A method as claimed in Claim 1 wherein the onlay of said second substance is affixed to said material by spraying.

11. A method as claimed in Claim 1 wherein the article is dried to remove water therefrom.

12. A hemostatic article comprising: a porous body; a first medicinal substance incorporated into said porous body; and a layer or coating of a second medicinal substance affixed to at least a portion of one surface of said porous body.

13. The hemostatic article of claim 12 wherein said second substance substantially covers said one surface of said porous body.

14. The hemostatic article of claim 12 wherein at least one of said first and second substances is a hemostatic agent formed of a modified collagen or collagen-like substance.

15. The hemostatic article of claim 12 wherein said porous body is a bandage, gauze, pad, strip or sponge, each of a natural of synthetic material.

16. A method for preparing a composite medical article which comprises: incorporating a first medicinal substance into a porous body; and affixing a layer of coating of a second medicinal substance upon at least a portion of one surface of said porous body and first hemostatic material.

17. The method of Claim 16 wherein the step of affixing a layer or coating of second medicinal substance comprises applying to said porous body, said second substance at least a portion or which is in liquid phase, and drying said liquid phase portion to affix said layer or coating of said second substance upon said portion of one surface of said porous body.

18. A method according to any of Claims 8, 9 and 10, wherein said first and second medicinal substances are hemostatic agents.

19. A method according to any of claims 16 and 17 wherein said first and second medicinal substances are hemostatic agents.

20. A hemostatic article prepared in accordance with any one of claims 3, 4 and 5.

21. A hemostatic article prepared in accordance with any one of claims 11, 16 and 17.