WO2009003062A1

WO2009003062A1 - Methods of performing minimally invasive surgery

Info

Publication number: WO2009003062A1
Application number: PCT/US2008/068233
Authority: WO
Inventors: Clark Adams; Peter Friedman; Charles W. Kerber
Original assignee: Valor Medical
Priority date: 2007-06-26
Filing date: 2008-06-25
Publication date: 2008-12-31

Abstract

Various methods for performing minimally-invasive surgery are provided. One method comprises the steps of forming a channel into a tissue of a patient, utilizing an instrument extending into the channel, withdrawing the instrument, and injecting a polymerizable cyanoacrylate material into the channel to seal the channel.

Description

METHODS OF PERFORMING MINIMALLY INVASIVE SURGERY

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 60/946,346, filed on June 26, 2007, entitled "Methods of Performing Minimally Invasive Surgery."

BACKGROUND OF THE INVENTION Field of the Invention

[0002] The invention generally relates to methods of performing minimally invasive surgery utilizing the step of injecting a polymerizable cyanoacrylate material into a tissue channel to seal the channel.

Description of the Related Art

[0003] Cyanoacrylates can be represented by formula I:

O

H₂C=I COR

CN I wherein R is an alkyl or other suitable substituent. Such cyanoacrylates are disclosed in U.S. Patent Nos. 3,527,224; 3,591,676; 3,667,472; 3,995,641; 4,035,334; and 4,650,826; the contents of which are hereby incorporated by reference in their entirety. Typically, when applied onto living tissue, the R substituent is an alkyl of from 2 to 10 carbon atoms.

[0004] Generally, cyanoacrylate is an acrylic resin that undergoes rapid polymerization in the presence of water. Exposure to moisture, specifically hydroxide ions, forms a strong polymer with long chains. One important trait of cyanoacrylates is that the material sets quickly, often in less than a minute. Accelerators may also be used to trigger setting in a matter of two or three seconds. [0005] Topical administration of cyanoacrylates has been used in medicine to hold human tissue together and to seal wounds. Ideally, for treating open type wounds or surgical incisions, the alkyl cyanoacrylate compositions should be formulated to be stable against premature, unintended polymerization and be of suitable viscosity for application to the skin. Also, the alkyl cyanoacrylate composition should polymerize rapidly and cure within from about four seconds to about 2 minutes after application. The resulting cured polymer should possess sufficient flexibility such that the integrity of the polymer coating is not compromised by, for example, cracking, etc. Finally, the cyanoacrylate composition should be non-toxic when injected into the wound and applied to skin.

[0006] It is also known that alkyl cyanoacrylate compositions can be employed in surgical environments as suture replacements or hemostats. When employed in these surgical environments, the parameters of the alkyl cyanoacrylate composition often diverge from the compositional parameters for topical application. For example, surgical application of the alkyl cyanoacrylate composition is typically over very specific, small total surface area internal parts of the human body and, accordingly, parameters such as viscosity, curing time, flexibility, durability, etc., are often different for this application as opposed to the parameters required for topical application.

[0007] Due to the ability to bond to human and other tissue, there exists a continuing need to develop inventive methods and uses of cyanoacrylates in surgical procedures.

SUMMARY OF THE INVENTION

[0008] Described herein are methods for performing minimally-invasive surgery. In an embodiment, the method comprises the steps of forming a channel into a tissue of a patient, utilizing an instrument extending into the channel, withdrawing the instrument, and injecting a polymerizable cyanoacrylate into the channel to seal the channel. Injection of the cyanoacrylate monomer or oligomer may take place from the instrument itself or from a cannula that is separate from the instrument. The polymerizable cyanoacrylate can advantageously be a monomer or a polymerizable oligomer. [0009] Also described herein are uses of a polymerizable cyanoacrylate in the preparation of a medicament for the treatment of a mammal during minimally-invasive surgery in which an instrument is withdrawn from a channel formed in the body of the mammal and the cyanoacrylate is injected into the channel to seal the channel. Any use that is described herein of a polymerizable cyanoacrylate in the preparation of a medicament for the various treatments discussed falls within the scope of the invention.

[0010] The methods described herein may be used in conjunction with various types of medical instrumentation. For example, any type of instrument that is inserted into tissue and forms or requires a channel may be used. In an embodiment, the instrument is a visualization instrument. In an embodiment, the instrument is a laparoscopic surgery instrument.

[0011] The methods of treatment described herein can be used in conjunction with any minimally-invasive surgical procedure known in the art. Preferably, minimally- invasive surgical procedures avoid openly invasive surgery and comprise closed or local surgery with less trauma than an equivalent procedure. Such procedures can be carried out through the skin, through a body cavity, or through an anatomical opening.

BRIEF DESCRIPTION OF THE DRAWINGS [0012] Figure 1 shows the formation of a channel in a tissue of a patient while utilizing an instrument within the channel.

[0013] Figure 2 shows cyanoacrylate polymer that has sealed the channel in the tissue of the patient.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT [0014] As used herein the term "alkyl cyanoacrylate" refers to an adhesive compound or mixture of compounds based on cyanoacrylate monomers of formula I:

O

H₂C=I COR

CN I wherein R is selected from the group consisting of alkyl of one to sixteen carbon atoms. Partial polymers (i.e., oligomers) of such cyanoacrylates are also encompassed within this definition. Preferred R alkyl groups are from 4 to 8 carbon atoms and include, by way of example, n-butyl, isobutyl, pentyl, n-hexyl, 2-hexyl, n-heptyl, 2-heptyl, n-octyl and 2-octyl. More preferably, R is 2-hexyl, isobutyl, 2-heptyl and 2-octyl and most preferably, R is 2- hexyl.

[0015] As used herein the term "alkyl" refers to a carbon chain of one to sixteen carbon atoms, where the carbon atoms can be linear or branched.

[0016] As used herein the term "lower-alkyl" refers to a carbon chain of one to eight carbon atoms, where the carbon atoms can be linear or branched. Examples of lower- alkyl moieties include but are not limited to methyl, ethyl, n-butyl, isobutyl, pentyl, n-hexyl, 2-hexyl, n-heptyl, 2-heptyl, n-octyl and 2-octyl.

[0017] As used herein the term "branched alkyl" refers to a carbon chain of one to sixteen carbon atoms where the carbon chain contains at least one secondary or tertiary substituted carbon atom.

[0018] As used herein the term "branched lower-alkyl" refers to a carbon chain of one to eight carbon atoms where the carbon chain contains at least one secondary or tertiary substituted carbon atom, for example, 2-hexyl, isobutyl, 2-heptyl and 2-octyl.

[0019] As used herein the term "biocompatible plasticizer" refers to any material which is soluble or dispersible in alkyl cyanoacrylate, which increases the flexibility of the resulting polymer coating on the skin surface, and which is compatible with the skin as measured by the lack of skin irritation. Suitable plasticizers are well known in the art and include those disclosed in U.S. Pat. Nos. 2,784,127 and 4,444,933 the disclosures of both of which are incorporated herein by reference in their entirety. Specific stabilizers include, by way of example only, acetyl tri-n-butyl citrate, butyl benzyl phthalate, dibutyl phthalate, diethyl phthalate, dimethyl phthalate, dioctylphthalate, n-butyryl tri-n-hexyl citrate, benzoate esters of di- and poly-hydroxy branched aliphatic compounds, tri(p-cresyl) phosphate, and the like. The particular plasticizer employed is not critical provided that it does not produce skin irritation as measured by well known assays such as primary skin-irritation (rabbit) as described in Example 3. Preferred plasticizers for use in this invention are citrates. [0020] As used herein the terms "adhesion" or "adhesive" means the characteristic or tendency of a material to be attracted to the surface of a second material. Adhesion occurs as the result of interactions between two materials. Depending on the characteristics of the second material relative to the first material, adhesion may or may not occur. For a single material, e.g., the composition of the present invention, the presence of adhesion is demonstrated by joining together separated human or animal tissue.

[0021] As used herein the term "cohesion" or "cohesive" means the characteristic or tendency of a material to stick together to itself. For example, this characteristic is demonstrated by a material or composition remaining intact as a single mass when introduced into a stationary fluid, or a fluid stream in motion, such as, blood. Lack of cohesive integrity results in the composition breaking up into multiple smaller subunits.

[0022] As used herein the term "alkyl esterified fatty acid" means a fatty acid derivatized to form an ester functional group with a alkyl moiety, such as ethyl myristate. These compounds are formed with an alkyl moiety, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl; and carboxylic acids with alkyl side chains ranging from 1 carbon, i.e., acetic acid, through to and including 17 carbons atoms in length, such as, proprionic, butyric, isobutyric, valeric, isovaleric, pivalic, lauric, myristic, palmitic and stearic acids.

[0023] As used herein the term "opacifϊcant agent" is compound or composition which selectively absorbs or deflects radiation making the material visible under x-ray, or any like imaging technique. Typically such agents include, iodinated oils, and brominated oils, as well as commercially available compositions, such as Pantopaque, Lipiodol and Ethiodol. These commercially available compositions acts as opacificant agents, and also dilute the amount of liquid monomer thereby slowing the rate of polymerization. In addition certain metals, such as, gold, platinum, tantalum, titanium, tungsten and barium sulfate and the like, have properties enabling them to act as opacificant agents.

[0024] As used herein the term "polymerization" refers to the chemical process where identical monomer units react chemically to form larger aggregates of said monomeric units as oligomers or polymers. [0025] As used herein the term "polymerization retardant" means an agent that can stop or slow down the rate of polymerization. Examples of such agents are pure phosphoric acid, and 85% phosphoric acid. Certain opacificant agents, such as Pantopaque, Lipiodol and Ethiodol can also function as a polymerization retardant by diluting the amount of liquid monomer and hence slowing polymerization rate.

[0026] As used herein the term "stability" refers to the ability of a monomer component to resist degradation or polymerization after preparation but prior to use.

[0027] As used herein the term "inhibitor agent" refers to an agent which stabilizes a monomer composition by inhibiting polymerization. Within the context of the current invention, this term refers to agents that stabilize and inhibit polymerization by various mechanisms. By altering the amounts of one or more inhibitor agents, the rate of polymerization can be controlled. Inhibitor agents have different modes of activity, for example, hydroquinone acts primarily to inhibit high energy free radicals; p-methoxyphenol acts primarily to inhibit low energy free radicals; and phosphoric acid influences the rate of anionic polymerization.

[0028] In an embodiment, there is provided a method for performing minimally- invasive surgery, the method comprising forming a channel into a tissue of a patient; utilizing an instrument extending into the channel; withdrawing the instrument; and injecting a polymerizable material into the channel to seal the channel. In some embodiments the polymerizable material is water-polymerizable. In some embodiments, the polymerizable material is cyanoacrylate monomer or oligomer. In some embodiments, the injected cyanoacrylate monomer is hexyl cyanoacrylate monomer.

[0029] In one embodiment, the cyanoacrylate monomer or oligomer is injected from the instrument directly. In another embodiment, the cyanoacrylate monomer or oligomer is injected from a cannula that is separate from the instrument. In still another embodiment, the cyanoacrylate monomer or oligomer is injected from a syringe.

[0030] Various types of instruments may be used with the minimally-invasive surgery methods described herein. For example, any instrument that extends into a channel in the tissue may be used with the methods described herein. In an embodiment, the instrument is a visualization instrument. For example, an endoscope may be used as the instrument. In one embodiment, the instrument is a laparoscopic surgery instrument. In an embodiment, the instrument is a biopsy instrument.

[0031] A channel is typically formed within a tissue of a patient either via use of the instrument within the channel or via creation of the channel using another instrument. The channel formed within the tissue may be of various types. For example, the channel may be a visualization channel or a laparoscope channel or both. In an embodiment, the method for performing minimally-invasive surgery seals both a visualization channel and a laparoscope channel.

[0032] The polymerizable material may include a variety of other types of ingredients in addition to the cyanoacrylate monomer or oligomer. In one embodiment, the polymerizable material further includes a biocompatible plasticizer. In a further embodiment, the polymerizable material further includes a visualizable material. The visualizable material can, for example, be radiologically visible. In a different embodiment, the visualizable material is an optical marker, which can advantageously be a dye. In some embodiments, the polymerizable material further includes an opacifant agent. In other embodiments, the polymerizable material further includes a polymerization retardant. The polymerizable material may contain not only cyanoacrylate monomer, but also viscosity-modifying material, such as cyanoacrylate polymer.

[0033] Where the polymerizable material comprises a visualizable material, the visualizable material may serve as a marker for where the instrument was placed within the tissue. Thus, the location or the area of the tissue that had been previously examined or previously treated can be easily identified at a later point in time for follow-up examination(s) and/or treatment(s).

[0034] Figure 1 shows an embodiment of the method described herein. An instrument (10) enters into tissue (12) through a contact point (14) and forms a channel (16) within the tissue. Alternatively, the channel may be formed using another device that is separate from the instrument. For example, a leading insertion device may be used to form the channel. Where the channel (16) is formed from the instrument (10), the shape of the channel may generally be similar in size and shape to the instrument (10) that is utilized within the tissue (12). Polymerizable material, such as cyanoacrylate monomer, may be stored within the instrument (10) and is readily injectible into the tissue via an opening (18) in the instrument. Alternatively, the polymerizable material can be injected into the tissue via a separate cannula (not shown).

[0035] The polymerizable material may be injected into the channel (16) as the instrument (10) is withdrawn from the channel. In an embodiment, the polymerizable material turns into a polymer in the presence of blood. For example, as cyanoacrylate monomer is injected into the channel, it quickly polymerizes upon contact with the intrinsic moisture present in the tissue, thus forming a polymerized substance and sealing the channel.

[0036] Figure 2 shows the tissue site containing the polymerized cyanoacrylate (20) after the instrument has been removed from the tissue (22). The polymerized cyanoacrylate (20) may be present from the entry point (24) where the instrument formed the channel (26) in the tissue extending part or all of the way to the most distal point at which the instrument penetrated the tissue. The polymerized cyanoacrylate (20) seals the channel left behind by the instrument and prevents bodily flood, such as blood, from leaking out of the tissue.

[0037] All patents incorporated by reference herein are incorporated by reference herein only with respect to the particular embodiments, materials, processes of manufacture and methods of use described therein. These patent are not to be considered incorporated by reference to the extent any of these patents expresses an opinion or presents any representation, characterization, or definition (either expressly or by implication) that is inconsistent with the opinions, representations, characterizations or definitions expressly made herein.

[0038] While there have been described herein what are to be considered exemplary and preferred embodiments of the present invention, other modifications of the invention will become apparent to those skilled in the art from the teachings herein. It is therefore desired to be secured in the appended claims all such modifications as fall within the true spirit and scope of the invention. Accordingly, what is desired to be secured by Letters Patent is the invention as defined and differentiated in the following claims.

Claims

WHAT IS CLAIMED IS:

1. Use of a polymerizable cyanoacrylate in the preparation of a medicament for the treatment of a mammal during minimally-invasive surgery in which an instrument is withdrawn from a channel formed in the body of the mammal and the cyanoacrylate is injected into the channel to seal the channel.

2. The use of Claim 1, wherein polymerizable cyanoacrylate is a monomer or oligomer.

3. The use of Claim 2, wherein the cyanoacrylate is injected from the instrument.

4. The use of any of Claims 2 through 3, wherein the cyanoacrylate is injected from a cannula separate from the instrument.

5. The use of any of Claims 2 through 4, wherein the injected cyanoacrylate is hexyl cyanoacrylate.

6. The use of any of Claims 1 through 5, wherein the instrument is a visualization instrument.

7. The use of any of Claims 1 through 6, wherein the instrument is a laparoscopic surgery instrument.

8. The use of any of Claims 2 through 7, wherein the injection is performed to seal both a visualization channel and a laparoscope channel.

9. The use of any of Claims 1 through 8, wherein the cyanoacrylate further includes a visualizable material.

10. The use of Claim 9, wherein the visualizable material is radiologically visible.

11. The use of Claim 9, wherein the visualizable material is an optical marker.

12. The use of Claim 11 , wherein the optical marker is a dye.

13. The use of any of Claims 2 through 5 or 8 through 12, wherein the instrument is a biopsy instrument.

14. A method for performing minimally-invasive surgery, comprising: forming a channel into a tissue of a patient; utilizing an instrument extending into the channel; withdrawing the instrument; and injecting a polymerizable cyanoacrylate into the channel to seal the channel.

15. The method of Claim 14, wherein the cyanoacrylate is injected from the instrument.

16. The method of any of Claims 14 through 15, wherein the cyanoacrylate is injected from a cannula separate from the instrument.

17. The method of any of Claims 14 through 16, wherein the injected cyanoacrylate is hexyl cyanoacrylate.

18. The method of any of Claims 14 through 17, wherein the instrument is a visualization instrument.

19. The method of any of Claims 14 through 18, wherein the instrument is a laparoscopic surgery instrument.

20. The method of any of Claims 14 through 19, wherein the method is performed to seal both a visualization channel and a laparoscope channel.

21. The method of any of Claims 14 through 20, wherein the cyanoacrylate further includes a visualizable material.

22. The method of Claim 21, wherein the visualizable material is radiologically visible.

23. The method of Claim 21, wherein the visualizable material is an optical marker.

24. The method of Claim 23, wherein the optical marker is a dye.

25. The method of any of Claims 14 through 17 or 20 through 23, wherein the instrument is a biopsy instrument.