AMENDMENT TO PROMISSORY NOTES

Exhibit 4.1

AMENDMENT TO PROMISSORY NOTES

This Amendment to Promissory Notes (this “Amendment”) is made as of this 10^th day of July, 2009 by and among Cardium Therapeutics, Inc., a Delaware corporation (the “Company”), and the Holders (as defined below) of the senior subordinated secured promissory notes issued pursuant to the terms of that certain Note and Warrant Purchase Agreement dated February 27, 2009 (“Purchase Agreement”). Capitalized terms used but not defined herein shall have the meanings ascribed to such terms in the Notes.

W I T N E S SE T H

WHEREAS, the Holders purchased an aggregate principal amount of $3,500,000 of senior subordinated secured promissory notes pursuant to the Purchase Agreement, of which an aggregate principal amount of $2,550,000 of Notes are dated February 27, 2009 and an aggregate principal amount of $950,000 of Notes are dated March 5, 2009, and each of which were amended by that certain Amendment to Promissory Notes dated as of June 23, 2009 by and among the Company and the Holders (such senior subordinated secured promissory notes as amended are referred to herein as the “Notes”);

WHEREAS, Section 10 of the Notes provides that the terms of all of the Notes may be amended with the written consent of the Company and the Requisite Holders; and

WHEREAS, Company and the Holders executing a signature page hereto, who collectively qualify as the Requisite Holders under the Notes (the “Consenting Holders”), desire to amend the terms of all of the Notes as set forth herein.

NOW, THEREFORE, for good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto hereby agree as follows:

1. Amendments. The Company and the Consenting Holders agree that, effective as of the date first above written, Section 5(a)(i) of the Notes is hereby amended to delete the words “fourteen (14) days” and in place thereof insert the words “twenty-three (23) days” so that Section 5(a)(i) of the Note shall read in its entirety as follows:

(i) any indebtedness under this Note is not paid when and as the same shall become due and payable, whether at maturity, by acceleration, thirty-five (35) days following notice of prepayment or otherwise, and any such amount shall remain unpaid for a period of twenty-three (23) days after the due date thereof;

2. Execution in Counterparts. This Amendment may be executed in any number of counterparts, each of which when so executed and delivered shall be deemed an original, and such counterparts together shall constitute one instrument. Delivery by facsimile or other electronic means of an executed counterpart hereof shall have the same force and effect as delivery of an originally executed counterpart hereof.

[Signatures on next page]

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IN WITNESS WHEREOF, the undersigned, by their duly authorized representatives, have executed this Amendment as of the date first above written.

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