IP Library › Granted Patent US 12,426,594
Granted Patent B2
US 12,426,594 · App. 17/482,898 · Granted Sep 30, 2025

Cryoprotective compositions and methods for protection of a surgical site during cryosurgery

Inventors: Franz Schmidlin (Geneva, CH); John Bischof (St. Paul, MN); Paul A. Iaizzo (White Bear Lake, MN); Qi Shao (Plymouth, MN); Pegah Ranjbartehrani (Falcon Heights, MN); David A. Ramirez (St. Paul, MN)
Assignees: Everest Medical Innovation GmbH; Regents of the University of Minnesota
A01N1/125A01N1/128A61B18/02A61B2018/00547A61B2018/00577A61B2018/0088A61B2018/0293
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Quick Facts
Patent No.
US 12,426,594
App. No.
17/482,898
Granted
Sep 30, 2025
Kind
B2
Abstract

A cryoprotective composition configured to be applied during cryotreatment of a patient includes at least one biodegradable and/or bioerodible fluid agent and at least one non-toxic cryoprotectant agent. A therapeutically effective amount of the cryoprotective composition deposited in a body space of the patient in proximity to the cryotreatment remains within at least a portion of the body space for a duration of the cryotreatment. At least a portion of a body tissue proximate to the body space is viable after the cryotreatment. A method of protecting a surgical site during prostate cryosurgery is also provided. The method includes injecting a therapeutically effective amount of the cryoprotective composition into the body space, wherein the body space is a periprostatic space of a patient.

Claims (41)

1. A method of protecting a surgical site during prostate cryosurgery comprising injecting a therapeutically effective amount of a cryoprotective composition into a periprostatic space surrounding a neurovascular bundle (NVB) adjacent to a prostate of a patient in proximity to the cryosurgery in order to separate the NVB from the surgical site

wherein the cryoprotective composition comprises:

at least one biodegradable and/or bioerodible fluid agent comprising a gel comprising from about 1 weight percent to about 10 weight percent of the cryoprotective composition; and

at least one non-toxic cryoprotectant agent contained in the gel, the at least one non-toxic cryoprotectant agent comprising Dimethyl sulfoxide (DMSO) and trehalose,

wherein the therapeutically effective amount of the cryoprotective composition deposited in the periprostatic space remains within at least a portion of the periprostatic space for a duration of the cryosurgery in order to maintain separation of the body tissue to be protected from the surgical site for the duration of the cryosurgery, and

wherein a majority of nerves of the NVB remain viable when exposed to a temperature of negative 10° C. during the cryosurgery and with the majority of the nerves having at least about a 30% action potential recovery following the cryosurgery.

2. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent comprises from about 1 weight percent to about 10 weight percent of the cryoprotective composition.

3. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent comprises Dimethyl sulfoxide (DMSO) comprising from about 1 weight percent to about 5 weight percent of the cryoprotective composition.

4. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent is free of ethylene glycol.

5. The method of claim 1 , wherein the duration of the cryosurgery is from about 10 minutes to about 5 hours.

6. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent causes less than about a 30% decrease of viability compared to saline and/or causes less than a 30% decrease of action potential amplitude compared to Krebs solution.

7. The method of claim 1 , wherein the cryoprotective composition does not cause substantial nerve damage when positioned in the periprostatic space for the duration of the cryosurgery.

8. The method of claim 1 , wherein the cryoprotective composition inhibits freezing and/or crystallization of the NVB and surrounding body tissue proximate to the periprostatic space when cryotherapy agents are used for the cryosurgery.

9. The method of claim 1 , wherein the therapeutically effective amount of the cryoprotective composition comprises an amount of the cryoprotective composition sufficient to inhibit freezing and/or crystallization of the NVB and surrounding tissue proximate to the periprostatic space when cryotherapy agents are used for the cryosurgery.

10. The method of claim 1 , wherein, when applied to the NVB of the patient, the cryoprotective composition does not substantially inhibit generation of action potentials by nerves of the NVB.

11. The method of claim 1 , wherein the cryoprotective composition further comprises at least one of Krebs phosphate solution or phosphate-buffered saline.

12. The method of claim 1 , wherein the at least one biodegradable and/or bioerodible fluid agent comprises at least one of cellulose and/or hyaluronic acid.

13. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent comprises Dimethyl sulfoxide (DMSO) comprising from about 1 weight percent to about 5 weight percent of the cryoprotective composition, and

wherein the at least one biodegradable and/or bioerodible fluid agent comprises hydroxyethyl cellulose comprising from about 1 weight percent to about 4 weight percent of the cryoprotective composition.

14. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent comprises Dimethyl sulfoxide (DMSO) comprising from about 1 weight percent to about 5 weight percent of the cryoprotective composition and from about 0.2M to about 0.4M trehalose, and

wherein the at least one biodegradable and/or bioerodible fluid agent comprises hydroxyethyl cellulose comprising from about 1 weight percent to about 4 weight percent of the cryoprotective composition.

15. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent comprises Dimethyl sulfoxide (DMSO) comprising about 5 weight percent of the cryoprotective composition and about 0.2M trehalose, and

wherein the at least one biodegradable and/or bioerodible fluid agent comprises hydroxyethyl cellulose comprising from about 1 weight percent to about 4 weight percent of the cryoprotective composition.

16. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent comprises Dimethyl sulfoxide (DMSO) comprising from about 1 weight percent to about 5 weight percent of the cryoprotective composition and from about 0.2M to about 0.4M trehalose, and

wherein the at least one biodegradable and/or bioerodible fluid agent comprises hyaluronic acid comprising from about 1 weight percent to about 4 weight percent of the cryoprotective composition.

17. The method of claim 1 , wherein the at least one non-toxic cryoprotectant agent comprises Dimethyl sulfoxide (DMSO) comprising about 5 weight percent of the cryoprotective composition and about 0.2M trehalose, and

wherein the at least one biodegradable and/or bioerodible fluid agent comprises hyaluronic acid comprising from about 1 weight percent to about 2 weight percent of the cryoprotective composition.

18. The method of claim 1 , wherein a size of a needle used for the injection of the cryoprotective composition into the periprostatic space ranges from an 18 gauge needle to a 22 gauge needle.

19. The method of claim 18 , wherein the injection is performed with ultrasound visualization of the needle and the periprostatic space with the patient in a lithotomy position.

20. The method of claim 19 , wherein the ultrasound visualization is provided by a transrectal ultrasound.

21. The method of claim 1 , wherein the injection of the cryoprotective composition to the periprostatic space comprises:

inserting a tip of a syringe needle through a perineum of the patient,

under ultrasound guidance, advancing the tip of the needle from an insertion site in the perineum to perforate a Denonvillier's fascia of the periprostatic space distal to the prostate,

injecting a first amount of the cryoprotective composition to a portion of the periprostatic space between the prostate and rectum, thereby separating a portion of the prostate comprising the surgical site from the rectum, and

continuing to inject the cryoprotective composition from the tip of the needle while retracting the needle from a base of the prostate to an apex of the prostate.

22. The method of claim 21 , wherein the injection of the cryoprotective composition to the periprostatic space further comprises injecting a second amount of the cryoprotective composition to spaces surrounding the NVB adjacent to the prostate, thereby separating the portion of the prostate comprising the surgical site from the NVB.

23. The method of claim 1 , wherein the cryoprotective composition is injected into the periprostatic space between a base of the prostate and an apex of the prostate.

24. The method of claim 1 , wherein the injected cryoprotective composition substantially or fully envelops the NVB of the patient adjacent to the prostate.

25. The method of claim 1 , wherein the cryosurgical procedure comprises tumor ablation of a prostate tumor.

26. The method of claim 1 , wherein the gel has a viscosity at about 20° C. to about 25° C. suitable to be ejected from a needle cannula into the body space.

27. The method of claim 1 , wherein the at least one biodegradable and/or bioerodible fluid agent remains as a gel at the temperature of negative 10° C.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 19, 2023
From: SCHMIDLIN, FRANZ
To: EVEREST MEDICAL INNOVATION GMBH
Reel/Frame 062423/0341 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 15, 2022
From: IAIZZO, PAUL A.; RAMIREZ, DAVID A.; SHAO, QI; RANJBARTEHRANI, PEGAH; BISCHOF, JOHN
To: REGENTS OF THE UNIVERSITY OF MINNESOTA
Reel/Frame 060804/0110 →
Continuity (2)
Provisional Application 63082790 · Sep 24, 2020
Related Publication 20220087250A1 · Mar 24, 2022
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