protect against enzymatic deamidation during production and/or storage ofa vaccine formulation. If the interpretation above is reasonably correct, then a complex or intermittent covalent bond between stabilizer and labile site would also be expected to limit enzymatic deamidation, by a sort of com- petitive inhibition at the labile site. Enzymatic deamidation is believed to occur in certain hepatitis vaccines, for example. 

Hemoglobin is known to undergo nonenzymatic deamida› tion, and while it is not a traditional active pharmaceutical ingredient, it is being investigated as a key ingredient in artificial blood (blood substitute), and thus formulations con› taining hemoglobin or related heme protein for blood substi› tutes are within the scope ofthis invention. 

Embodiments of the current invention can be used for many routes of administration compatible with peptide or protein delivery, including but not limited to parenteral, intra› venous, intraperitoneal, intrathecal, intramuscular, subcuta› neous, intra-arterial, rectal, intravaginal, sublingual, intraocular, transdermal, intranasal, via inhalation, in a sup› pository, ophthalmic, and others. Oral delivery of peptides and proteins is currently a largely unsolved problem, although several promising approaches have made progress, and the invention may be compatible with some such formu› lations. 

It should be noted that while the primary function of the current invention is to minimize or prevent deamidation, other degradation reactions occurring in the formulations of the invention might also be concomitantly reduced by the stabilizing anion(s). This is particularly true for other base› catalyzed reactions involving carbonyl groups. 

A deamidation-prone decapeptide with two labile aspar› aginyl residues was shown in this Example to be stabilized against deamidation by the current invention; the Example also shows the destabilizing effect of anions such as acetate and phosphate. To begin with, a decapeptide was synthesized by request at the Protein Facility of the Iowa State University Office of Biotechnology, using standard peptide synthesis methodology. The peptide had the sequence RCNSGR› FNGG-NH2 (Arg-Cys-Asn-Ser-Gly-Arg-Phe-Asn-Gly-Gly, terminal amide). Literature on peptide degradation by deami› dation at asparagine sites shows by overwhelming consensus that the FNG and CNS subsequences are prone to degrada› tion. 

Samples containing this decapeptide were prepared under eight different conditions at two different pH values, pH 7 and 4. The 200 mM arginine/I 00 mM phosphate buffer was only prepared at pH 7. The preparation of these samples is now described. The ratios indicated are molar ratios of organic anion to decapeptide. 

HCI-Control. 

Into a sterile 15 mL plastic centrifuge tube (Coming Incor› porated, Coming, N.Y.) was placed 0.0021 g decapeptide (Iowa State University, Ames, Iowa) and 7.0 g sterile water (Spectrum Chemicals Mfg. Corp., Gardena, Calif.). The pH was adjusted using I .ON HCl (Spectrum Chemicals Mfg. Corp., Gardena, Calif.)to a pH of 4. Into anew 15 mL plastic centrifuge tube was placed 3 .5 mL of a pH 4 solution. The pH was adjusted using only the necessary amount of I .ON NaOH (Spectrum Chemicals Mfg. Corp., Gardena, Calif.) to a final pHof7. 

Saccharin:Decapeptide, 1: 1 

## EXAMPLES 

## Example 1 

( anion:asparaginyl molar ratio). Into a sterile 15 mL plastic centrifuge tube was placed 0.0021 g decapeptide, 0.0011 g sodium saccharin (Spectrum Chemicals Mfg. Corp., Gar› dena, Calif.) and 7.0 g sterile water. The pH was adjusted using only the necessary amount of saccharin (Spectrum Chemicals Mfg. Corp., Gardena, Calif.) to a pH of 4. Into a new 15 mL plastic centrifuge tube was placed 3 .5 mL of a pH 4 solution. The pH was adjusted using only the necessary amount of I .ON Na OH to a final pH of 7. 

Saccharin:Decapeptide, 3: 1 

Into a sterile 15 mL plastic centrifuge tube was placed 0.0021 g decapeptide, 0.0029 g sodium saccharin and 7.0 g sterile water. The pH was adjusted using only the necessary amount of saccharin to a pH of 4. Into a new 15 mL plastic centrifuge tube was placed 3 .5 mL of a pH 4 solution. The pH was adjusted using only the necessary amount of 1.0NNaOH to a final pH of 7. 

Saccharin:Decapeptide, 10: 1. 

Into a 15 mL plastic centrifuge tube was placed 0.0021 g decapeptide, 0.0095 g sodium saccharin and 7.0 g sterile water. The pH was adjusted using only the necessary amount of acid saccharin to a pH of 4. Into a new 15 mL plastic centrifuge tube was placed 3 .5 mL of a pH 4 solution. The pH was adjusted using only the necessary amount of 1.0NNaOH toafinalpHof7. 

Acetate:Decapeptide, 3: 1. 

Into a sterile 15 mL plastic centrifuge tube was placed 0.0021 g decapeptide, 0.0016 g sodium acetate (Spectrum Chemicals Mfg. Corp., Gardena, Calif.) and 7.0 g sterile water. The pH was adjusted using only the necessary amount of acetic acid (Spectrum Chemicals Mfg. Corp., Gardena, Calif.) to a pH of 4. Into a new 15 mL plastic centrifuge tube was placed 3.5 mL of a pH 4 solution. The pH was adjusted using only the necessary amount of I .ON NaOH to a final pH of7. 

Acetate/Saccharin:Decapeptide, 3/10: 1. 

Into a sterile 15 mL plastic centrifuge tube was placed 0.0021 g decapeptide, 0.0016 g sodium acetate, 0.0094 g sodium saccharin and 7 .0 g sterile water. The pH was adjusted using only the necessary amount of acid saccharin to a pH of 4. Into a new 15 mL plastic centrifuge tube was placed 3 .5 mL of a pH 4 solution. The pH was adjusted using only the necessary amount of I .ON Na OH to a final pH of 7. 

Into a sterile 1.5 mL microcentrifuge tube was placed a 0.5 g portion of each sample condition and were placed at -18° C. This was the initial sample. The remaining pH 4 samples were placed at 65° C. until completion of the experiment. The remaining pH 7 samples were placed at 40° C. until comple› tion of the experiment. Into a sterile 1.5 mL microcentrifuge tube was placed a 0.5 g portion of each sample condition on "day 1", 24 hours after preparation, and were placed at -18° C. This was the day 1 sample. The frozen initial and day 1 samples were thawed to room temperature, and assayed using HPLC. 

Chromatographic analysis. 

The samples at the various timepoints were then analyzed with HPLC using the following conditions. 

System: Schimadzu SCL-l0A VP with diode array detector 

Colunm: Phenomenex C18 Luna 5 um, 250x4.6 mm 

Mo bile Phase: Isocratic 90% ( 0 .1 % ) TF A in water, 10% (0.08%) TFA in acetonitrile 

Flow Rate: 1.0 mL/min 

Wavelength: 214 nm 

The potency (mg/mL of intact peptide) was determined by integrating under this peak (performed by the instrument), and normalizing according to a standard run of the decapep› tide. The relative potency was then calculated by dividing the 

