The importance of purity and formula of N-acetylcarnosine - the importance of detail, in the correct manufacturing of pharmaceutical agents.

The importance of purity and formula of N-acetylcarnosine - the importance of detail, in the correct manufacturing of pharmaceutical agents.

At the 1st Paris Anti-Aging Conference, February, 2003, Dr. Babizhayev talked about the Russian breakthrough of N-acetylcarnosine for the treatment of senile cataract. IAS took the opportunity to interview Dr. Babizhayev further, about the precise role of N-acetylcarnosine and a number of important factors were raised in the discussion.

Phil: "Dr. Babizhayev, thank you very much for joining me here today, to discuss your important breakthrough of an eye-drop to treat, and possibly to prevent senile cataract. I know by the response that the readers of the IAS Anti-Aging Bulletin, enjoyed our previous discussion."

Dr. Babizhayev: "It's a pleasure to be in Paris with you Phil."

Phil: "As you know, we have already covered a lot in our previous article and interview, (Ed.- IAS Anti-Aging Bulletin, Winter 2001), about the development of N-acetylcarnosine and its role in combating the common aging-disease of senile cataract. We were made very aware in those, that there are significant differences between L-carnosine and n-acetylcarnosine, and we warned everyone then that they shouldn't use L-carnosine for eye-use. But tell us, are there any differences in N-acetylcarnosine itself?"

Dr. Babizhayev: We have developed a very precise product of N-acetylcarnosine, both from the point of view of purification, and its content of transition metal ions traces. This is because, rather uniquely, only certain types and levels of impurities enable the maintenance of the peculiar antioxidant activities of the released molecule, including those scavenging the hydroxyl radical, singlet oxygen, lipid peroxidase-like and ferroxidase-like activities. This very particular active product is responsible for the anti-cataract efficacy, and for the protection of the lens proteins from the singlet oxygen-induced oxidation of the lens protein, specifically the aminoacid tryptophan residues, which have been measured using chemiluminescenece technique and L-Gly-Tryptophan peptide. Some details of this were published in one of our papers. (Ed.- see reference 1 below).

Phil: "So, when you were experimenting with your different N-acetylcarnosines, was there a difference in their efficacy, or side effects?

Dr. Babizhayev: "Oh yes, sure! With either too much or too little metals side-effects were caused, or we saw less efficacy. The manifested lipid hydroperoxides scavenging activities of the released carnosine, and the ferroxidase activities of the final released product in the eye are all very important."

Phil: "Thus, I imagine, you must have decided upon a specific N-acetylcarnosine with a narrow range of purity, that was, in terms of its impurities, not-too-much, not-too-little. Is that form commonly available?

Dr. Babizhayev: "No, that form is not commonly available, and the information is kept proprietary. The specific N-acetylcarnosine in question, is manufactured by our Japanese partner under a cGMP specific know-how process. Therefore, this material is currently only available from one source, which is Innovative Vision Products, the patent holders."

Phil: "So how can people tell if they are using the correct material in their eye-drop?"

Dr. Babizhayev: "The packaging should clearly state that the formula is approved and patented by Innovative Vision Products/ IVP."

Phil: "Now we understand the importance of the type of carnosine and its purity for eye-drops. Are there any problems in the formula? By which I mean, what happens if you start to change the formula by adding additional ingredients etc?"

Dr. Babizhayev: "Innovative Vision Products, Inc. has conducted serious pharmacokinetic studies utilizing precise chromatographic techniques of analysis, and using the final formulated patented Can-C ® product and other various possible formulations. The ratio of carnosine/NAC concentrations upon the topical application of Can-C ® to the eye, is equal to 9 in the aqueous humor. This means that virtually all N-acetylcarnosine is converted to the more powerful antioxidant L-carnosine in the aqueous humor. This can then enter the lens tissue and epithelial cells, and act as the anti-cataract remedy.

The deacetylation of N-acetylcarnosine by N-acetylesterases and N-acetyltransferases, at the level of the cornea and the conjunctiva, can be inhibited with the voluntary addition of other substances to the ophthalmic formulation, substances such as vitamin E and vitamin A. This is because they are endowed with a branched hydrophobic hydrocarbon skeleton. Such formulas, that do not originate from the validated source of 1% N-acetylcarnosine, when applied, can be readily hydrolyzed at the peptide bond site and then allergic histamine is released because of the peptide hydrolysis with acid hydrolases in the tear fluid.

N-acetylcarnosine is a delicate molecule. The biotransformation of N-acetylcarnosine into L-carnosine in unsolicited external topical formulations, can be promptly inhibited. Active L-carnosine can not be detected in the aqueous humor after the topical installation of hydrophobic vitamin-loaded remedies after 15 minutes, at any significant doses. It is not apparent that when chemicals are mixed together, chemicals which, by themselves may have efficacy, that the sum is greater than the single parts. These chemicals interact with one another, and in the eye, these additional interactions could cause side effects or lose the efficacy of the original product."

Phil: "As I understand it, now we know that the amount of transformation of N-acetylcarnosine into L-carnosine, and the length of life/ activity of that L-carnosine in the aqueous humor are all essential elements in the efficacy of N-acetylcarnosine eye-drops. I therefore suspect that you must be concerned about copy-cat products that claim your research, but actually contain inferior N-acetylcarnosine and formulas that have little value?"

Dr. Babizhayev: "Yes, I fear that such inferior products will mar my entire research and maybe people will think that all N-acetylcarnosine is the same, and that eventually it will block even the correct product and formula from coming to market. However, myself and our shareholders are addressing this issue, and in those countries where such products are currently being used, our patents there will be in force later this year and we shall pursue them."

Phil: "I guess it's actually part of that old adage, when we say, the devil is in the detail."

Dr. Babizhayev: "Indeed it is Phil."

Phil: "I appreciate that it is still early days, but do you feel, or do you have any scientific reasoning, if N-acetylcarnosine will be useful in other eye-disorders?"

Dr. Babizhayev: "Yes, we believe that N-acetylcarnosine will have a role for glaucoma, especially when combined with some other substances that we are currently working on. In particular, we know that N-acetylcarnosine is efficacious for its anti-glare effect and improvement for color vision. So, for example, we envisage that this could lead to safer driving, especially night driving, and I am sadly reminded about the tragic death of Princess Diana whenever I think of this.

Another interesting, recent development is the fact that we have shown N-acetylcarnosine to prevent and reverse the acidosis in the corneal stroma due to the actions of accumulated lactic acid. This means that individuals can wear contact lenses, particularly soft contact lenses, which are not gas permeable, for longer and with more comfort."

Phil: "Have you enjoyed yourself here in Paris? I mean, professionally of course! What kind of response are you getting to your trials that show n-acetylcarnosine to be highly efficacious in the prevention and treatment of senile cataract?"

Dr. Babizhayev: "Yes, the response wherever I go is very favorable and I think that eventually the word about this breakthrough is going to spread worldwide. We are close to some arrangements that would probably mean the general media would know and report about this, when that happens I expect much will change quickly."

Phil: "I'm sure there will continue to be some resistance to this breakthrough, after-all, it always takes some time to accept new ideas, and especially for the mainstream media to start reporting on it. But then, that's why people read the IAS Anti-Aging Bulletin, to be ahead of the crowd, and keep up-to-date on the cutting-edge."

Dr. Babizhayev: "Yes, I believe it is a most worthy enterprise."

Phil: "Thank you for your time with us here today and enjoy the rest of your stay in Paris.

Dr. Babizhayev: "Thank you, I will."

References:

  1. Babizhayev MA, Lozovskaya EL, Makareyeva EN, Lulkin YA, Sapezhinskii II, "Photoprotector and antioxidant properties of histamine containing peptidomimetics in the photooxidation of glycyltryptophan." Biochemistry (Moscow), 1998 May;63(5):523-8.