Aqueous radiation protecting formulations and methods for making and using them

• US 8,999,720 B2
• Filed: 10/25/2012
• Issued: 04/07/2015
• Est. Priority Date: 11/17/2011
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Kristensen, Jesper Svenning, Aasmul, Soren
• Primary Examiner(s): Mui, Christine T
• Application Number:
  US13/660,648
• Publication Number:
  US 20130130395A1
• Time in Patent Office: 894 Days
• Field of Search: 436/95, 436/94, 436/93, 436/91, 422/22, 422/1
• US Class Current: 436/95
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 2562/18 Shielding or protection of sensors from environmental influences, e.g. protection from mechanical damage
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61L 2/02 using physical phenomena
• CPC Class Codes: A61L 2/081 Gamma radiation
• CPC Class Codes: A61L 2/087 Particle radiation, e.g. electron-beam, alpha or beta radiation
• CPC Class Codes: A61L 2202/14 Means for controlling sterilisation processes, data processing, presentation and storage means, e.g. sensors, controllers, programs
• CPC Class Codes: A61L 2202/24 Medical instruments, e.g. endoscopes, catheters, sharps
• CPC Class Codes: G01N 2400/00 Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
• CPC Class Codes: G01N 2458/00 Labels used in chemical analysis of biological material
• CPC Class Codes: G01N 33/5308 for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: Y10T 436/14 Heterocyclic carbon compound [i.e. , O, S, N, Se, Te, as only ring hetero atom]
• CPC Class Codes: Y10T 436/142222 Hetero-O [e.g., ascorbic acid, etc.]
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

Medical devices are typically sterilized in processes used to manufacture such products and their sterilization by exposure to radiation is a common practice. Radiation has a number of advantages over other sterilization processes including a high penetrating ability, relatively low chemical reactivity, and instantaneous effects without the need to control temperature, pressure, vacuum, or humidity. Unfortunately, radiation sterilization can compromise the function of certain components of medical devices. For example, radiation sterilization can lead to loss of protein activity and/or lead to bleaching of various dye compounds. Embodiments of the invention provide methods and materials that can be used to protect medical devices from unwanted effects of radiation sterilization.

Claims

1. A method of inhibiting damage to a saccharide sensor that can result from a radiation sterilization process, the method comprising combining the saccharide sensor with an aqueous radioprotectant formulation during the sterilization process, wherein:

the saccharide sensor comprises a saccharide binding polypeptide having a carbohydrate recognition domain;

the aqueous radioprotectant formulation comprises a saccharide selected for its ability to bind the saccharide binding polypeptide; and

performing the sterilization process under conditions selected so that the saccharide binds the saccharide binding polypeptide, thereby inhibiting damage to the saccharide sensor that can result from the radiation sterilization process.

2. The method of claim 1, wherein the saccharide binding polypeptide comprises mannan binding lectin, concanavalin A or glucose oxidase.

3. The method of claim 1, wherein the saccharide comprises glucose, mannose, fructose, melizitose, N-acetyl-D-glucosamine, sucrose or trehalose.

4. The method of claim 1, wherein the aqueous radioprotectant formulation comprises an antioxidant selected from the group consisting of ascorbate, urate, nitrite, vitamin E, α

-tocopherol or nicotinate methylester.

5. The method of claim 1, wherein:

the saccharide sensor comprises a fluorophore; and

the aqueous radioprotectant formulation comprises a fluorophore quenching composition selected for its ability to quench the fluorophore.

6. The method of claim 1, wherein the aqueous radioprotectant formulation comprises a buffering agent.

7. The method of claim 6, wherein the buffering agent is selected from the group consisting of citrate, tris(hydroxymethyl)aminomethane (TRIS) and tartrate.

8. The method of claim 1, wherein the radiation sterilization process comprises a single dose of radiation.

9. The method of claim 1, wherein the radiation sterilization process comprises electron beam irradiation.

10. A composition of matter comprising:

a saccharide sensor comprising;

a saccharide binding polypeptide having a carbohydrate recognition domain; and

a fluorophore; and

an aqueous radioprotectant formulation comprising;

a saccharide, wherein the saccharide is bound to the carbohydrate recognition domain;

an antioxidant compound, wherein the antioxidant compound is selected from the group consisting of ascorbate, urate, nitrite, vitamin E, α

-tocopherol or nicotinate methylester; and

a fluorophore quenching composition.

11. The composition of claim 10, wherein the fluorophore quenching composition comprises acetaminophen.

12. The composition of claim 11, wherein the aqueous radioprotectant formulation comprises acetaminophen in a concentration of at least 1 mM to 50 mM.

13. The composition of claim 10, wherein the aqueous radioprotectant formulation comprises ascorbate in a concentration of at least 1 mM to 100 mM.

14. The composition of claim 10, wherein the saccharide is selected from the group consisting of glucose, mannose, fructose, melizitose, N-acetyl-D-glucosamine, sucrose or trehalose.

15. The composition of claim 14, wherein the aqueous radioprotectant formulation comprises mannose in a concentration of at least 1 mM to 100 mM.

16. The composition of claim 14, wherein the aqueous radioprotectant formulation comprises sucrose in a concentration of at least 10 mM to 1000 mM.

17. The composition of claim 10, wherein the aqueous radioprotectant formulation comprises a buffering agent;

and has a pH of 6 or below.

18. The composition of claim 17, wherein the buffering agent is selected from the group consisting of citrate, tris(hydroxymethyl)aminomethane (TRIS) and tartrate.

19. The composition of claim 10, wherein the aqueous radioprotectant formulation comprises a surfactant.