Biostable glucose permeable polymer

• US 9,848,805 B2
• Filed: 12/18/2015
• Issued: 12/26/2017
• Est. Priority Date: 12/18/2015
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Dang, Tri T., Egesborg, Henrik, Janting, Jakob, Shah, Rajiv, Aaskov, Daniel, Hall, Joseph F., Aasmul, Soren
• Primary Examiner(s): Wecker, Jennifer
• Application Number:
  US14/974,250
• Publication Number:
  US 20170172471A1
• Time in Patent Office: 739 Days
• CPC Class Codes: A61B 2090/306 using optical fibres
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: C08G 18/3221 hydroxylated esters of carboxylic acids other than higher fatty acids
• CPC Class Codes: C08G 18/4837 and other oxyalkylene units
• CPC Class Codes: C08G 18/5024 containing primary and/or secondary amino groups
• CPC Class Codes: C08G 18/758 containing two or more cycloaliphatic rings
• CPC Class Codes: C08G 71/02 Polyureas
• CPC Class Codes: C08L 75/00 Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer composition, and methods for making and using such sensor systems.

Claims

1. A glucose sensing system comprising:

a tubular housing having a first end and a second end, wherein;

the tubular housing comprises a polymeric composition formed by combining;

an isocyanate;

a polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol having an average molecular weight (M_r) of from about 600 to about 1200 Daltons; and

a terephthalate; and

the polymeric composition has a glucose permeability of at least 1×

10<sup>−

8</sup> cm²/s at 37°

C. in phosphate buffered saline.

2. The glucose sensing system of claim 1, wherein the polymeric composition is biostable such that the tubular housing has less than a 5% weight loss after 7 days of implantation in vivo.

3. The glucose sensing system of claim 1, wherein:

(a) the first end of the tubular housing is coupled to an optical fiber so as to form a seal with the first end; and

/or

(b) the second end of the tubular housing is coupled to a membrane or a cap, thereby forming an internal reservoir within the tubular housing.

4. The glucose sensing system of claim 3, wherein the tubular housing is coupled to the optical fiber and/or the cap by solvent bonding such that polymers in the polymeric composition and polymers in the optical fiber or polymers in the cap are entangled and attracted together by Van der Waals forces.

5. The glucose sensing system of claim 3, wherein the tubular housing comprises:

(a) an internal reservoir containing a glucose sensing complex comprising at least one glucose binding agent and at least one fluorophore; and

(b) the components of (a) are lyophilized.

6. The glucose sensing system of claim 1, wherein the tubular housing is between 80 microns and 300 microns in diameter.

7. The glucose sensing system of claim 3, wherein the internal reservoir comprises a hydrogel.

8. The glucose sensing system of claim 3, wherein the internal reservoir is disposed on a side of the tubular housing.

9. The glucose sensing system of claim 5, further comprising:

a processor, wherein the processor performs the steps of;

assessing optical signal data generated by the glucose sensing complex and transmitted by the optical fiber; and

computing a glucose concentration based upon the optical signal data.

10. A method for making a glucose sensor comprising the steps of:

(a) combining together an isocyanate, a polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol having an average molecular weight (M_r) of from about 600 to about 1200 Daltons; and

a terephthalate;

(b) allowing the combination of (a) to form a polymeric composition having a glucose permeability of at least 1×

10<sup>−

8</sup> cm²/s at 37°

C. in phosphate buffered saline;

(c) using an extrusion process to mold the polymeric composition into a tubular housing having a first end and a second end.

11. The method of claim 10, wherein the method comprises operatively coupling the first end of the tubular housing to an optical fiber so as to form a seal with the first end.

12. The method of claim 11, wherein the method comprises operatively coupling the second end of the tubular housing to a membrane or a cap so as to form a seal with the second end and an internal reservoir within the tubular housing.

13. The method of claim 12, further comprising disposing a hydrogel in the internal reservoir.

14. The method of claim 12, wherein the cap is formed from the polymeric composition and is coupled to the second end using a solvent to dissolve the polymeric composition and create adhesion between the cap and the second end of the tubular housing.

15. The method of claim 14, wherein the cap is coupled to the tubular housing using a solvent vapor.

16. The method of claim 10, wherein the method comprises disposing a lyophilized glucose sensing complex within the internal reservoir.

17. The method of claim 10, wherein the tubular housing is between 80 microns and 300 microns in diameter.

18. The method of claim 10, wherein the polymeric composition is formed to exhibit a less than a 10% weight loss after 7 days of implantation in vivo.

19. The method of claim 10, wherein the polymeric composition is formed from polymers having an average molecular weight of between 10,000 and 1,000,000 Daltons.

20. A hydrophilic polyurea composition shaped to form a tubular housing, and formed by combining:

an isocyanate,

a polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol having an average molecular weight (M_r) of from about 600 to about 1200 Daltons; and

a terephthalate;

wherein;

the hydrophilic polyurea composition has a glucose permeability of at least 1×

10<sup>−

8</sup> cm²/s at 37°

C. in phosphate buffered saline and

wherein the hydrophilic polyurea polymeric composition is biostable such that the tubular housing has less than a 5% weight loss after 7 days of implantation in vivo.