32 replies to this topic

[Daniel Cooper]

Based on this paper Rosmarinic Acid Restores Complete Transparency of Sonicated Human Cataract Ex Vivo and Delays Cataract Formation In Vivo and the absence of any commercial eye drop containing rosmarinic acid (RA), I'm toying with the idea of making my own DIY RA eye drops to address some early cataract formation.

This isn't something I take lightly. There's no clinical data whatsoever on topical RA for cataracts in humans, and I've very aware of the need to follow sterile procedures when making the preparation.

I'm thinking of making a 1% w/v solution. Clearly I'll need sterile distilled water and rosmarinic acid and a good scale. I suspect I'll also want to add a buffering agent to keep the pH in an acceptable range (say 6.0 - 8.0). Does anyone have any suggestions for a buffer agent? Clearly we don't want to neutralize the rosmarinic acid but we also don't want the pH going too low. I do have a digital pH meter and calibration solutions. 

 

Suggestions would be welcome.
 

 

[Daniel Cooper]

Forgot to add.  RA is only slightly soluble in water. It is well soluble in most organic solvents and I believe it can be reasonably soluble in water if the right buffer agent is used.

 

I can't think of many organic solvents that I want to put in my eye, except maybe a very dilute solution of water + DMSO (which has actually been used at least experimentally in the eye in the past).  I suppose you might suspend it in olive oil or castor oil, however I would bet you'd get better permeability into the lens capsule with H20 + buffer or H20 + DMSO.

 

Again, comments from better chemists than I would be appreciated. 

 

 

 

[Rays]

Interesting experiment.
Why not add some NMN?
Will you experiment on one eye only? To judge whether it has any effect?

[Daniel Cooper]

I'm a little reluctant to just throw in things that "seem like a good idea" unless I have some evidence for effectiveness for cataracts.  

 

I could see that NR/NMN might be useful topically in the eye, but it would be nice to know that for sure.  I doubt it would hurt anything however.

 

And yes, I'd certainly start in one eye till I was comfortable with safety.  However, I think whether is effective will probably be obvious.  Either the cataract regresses or not.  They rarely (though not never) regress on their own.

 

 

[nickdino]

Interesting test man! Please keep us informed

[Oakman]

Interesting DIY. I used this as a base for some DIY eye drop experiment I did previously. Since it already has been shown (from reviews) harmless in the eye, I think it would be a good starting point. Good luck and keep us informed of your progress.

Edited by Oakman, 09 August 2019 - 04:22 PM.

[Rays]

How's it going, Daniel? Did you start your experiment?

 

[Rays]

Interesting DIY. I used this as a base for some DIY eye drop experiment I did previously. Since it already has been shown (from reviews) harmless in the eye, I think it would be a good starting point. Good luck and keep us informed of your progress.

 

The link didn't work; it went back to the same page. Can you post it again?

[Oakman]

The link didn't work; it went back to the same page. Can you post it again?

 

https://www.amazon.c...e?ie=UTF8&psc=1

[Daniel Cooper]

My biggest issue right now is -

 

• I'm having trouble sourcing rosmarinic acid.  Rosemary extract I can find, but it may have other constituents that I don't want to put in my eye.
• I need a buffer to make the rosmarinic acid more soluble in water.  I'm thinking a phosphate buffer but my knowledge in this area needs some work.

  

[smithx]

Feeling helpful tonight. This is not an endorsement of the idea, since I haven't even read the paper yet:

 

 

Sources of rosmarinic acid:

https://www.caymanch...m/catalog/70900

https://www.sigmaald...ace=CAS No.&N=0

https://www.phytopur...acid-p-290.html

https://us.vwr.com/s...marinic-acid-97

http://www.kaimosi.com/n.html - Chinese - "free sample"

 

Solubility

Soluble in: water, 1425 mg/L @ 25 °C (est)

http://www.thegoodsc.../rw1372331.html

0.14% (ish)

 

Soluble in ethanol, DMSO or dimethyl formamide to approximately 25 mg/mL

https://pubchem.ncbi...tion=Color-Form
 
 

Rosmarinic  acid  is  supplied  as  a  crystalline  solid.  A  stock  solution  may  be  made  by  dissolving  the  rosmarinic acid in an organic solvent. Rosmarinic acid is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide. The solubility of rosmarinic acid in these solvents is approximately 25 mg/ml.Further  dilutions  of  the  stock  solution  into  aqueous  buffers  or  isotonic  saline  should  be  made  prior  to  performing biological experiments. Ensure that the residual amount of   organic solvent is   insignificant, since organic solvents may have physiological effects at low concentrations. Organic solvent-free aqueous solutions  of  rosmarinic  acid  can  be  prepared  by  directly  dissolving  the  crystalline  compound  in  aqueous  buffers. The solubility of rosmarinic acid in PBS (pH 7.2) is approximately 15 mg/ml. We do not recommend storing the aqueous solution for more than one day

https://www.caymanch.../pdfs/70900.pdf

 

 

 

PBS - Phosphate Buffered Saline - 7.2pH

https://www.thermofi...roduct/20012027

 

But:

 

Eye:May cause eye irritation.

http://www.uccaribe....ered-saline.pdf

 

So how about:

 

Sensitive Eyes Saline Solution

Boric Acid, Sodium Borate, Potassium Chloride, Sodium Chloride, Polyaminopropyl Biguanide, Edetate Disodium

https://www.walgreen...1684212-product

 

[VivienGFFR]

https://www.coc.it/e...dose-containers

 

 

[YOLF]

https://www.amazon.c...e?ie=UTF8&psc=1

MSM drops? Or did the Amazon seller change the listing to something else?

Edited by YOLF, 20 January 2020 - 01:11 AM.

[YOLF]

https://www.coc.it/e...dose-containers

 

This eye drop looks interesting. From a contract manufacturer too. Sounds like a business opportunity.

[Oakman]

MSM drops? Or did the Amazon seller change the listing to something else?

 

No they haven't changed. read the 2nd bullet in the listing. Says eye drops, yes? Yes.

[Daniel Cooper]

https://www.coc.it/e...dose-containers

 

I would love to get ahold of some of that. But can't justify starting up a business to try to import it.

[VivienGFFR]

I emailed them to ask for a sample but nothing. Maybe I will try LEF Brite Eye III for my corticotherapy induced cataract and give it a try before regular surgery as this would be a bit tricky in my case.

[Daniel Cooper]

I emailed them to ask for a sample but nothing. Maybe I will try LEF Brite Eye III for my corticotherapy induced cataract and give it a try before regular surgery as this would be a bit tricky in my case.

 

 

I tried Brite Eye III for three months and nothing.  The problem is that all the research showing a positive effect on cataracts from those N-Acetylcarnosine drops was done by the same Russian group that holds the patent.  I've seen no independent research that shows it is effective so far.

[VivienGFFR]

I tried Brite Eye III for three months and nothing.  The problem is that all the research showing a positive effect on cataracts from those N-Acetylcarnosine drops was done by the same Russian group that holds the patent.  I've seen no independent research that shows it is effective so far.

 

Ok thanks for sharing your experience. So you would preferably recommand a rosmarinic acid product ?

[Daniel Cooper]

Ok thanks for sharing your experience. So you would preferably recommand a rosmarinic acid product ?

 

 

Oh heaven no.  The only thing I know is that rosmarinic acid solutions cleared cloudy lens in vitro. I haven't seen an animal or human study.  I don't think anyone's done one yet. I just think I can make a relatively weak rosmarinic acid solution that is very unlikely to be harmful that might help with cataracts.  

 

At this point the only opinion I have is on what doesn't work. From my experience, N-Acetylcarnosine drops don't work (or at least didn't for me) nor did Lanosterol eye drops work.  

 

Rosmarinic acid shows one of the strongest cataract reversal effects in vitro. Whether or not that would translate into an in vivo effect is anyone's guess.  But, when you're trying to reverse or at least delay cataracts, there aren't many games in town.  As long I think it won't hurt me, I'm willing to give it a try.  But what I'm willing to try should have no influence on you.  I'm not a doctor after all.

 

The only other thing out there that is under clinical study is EV-06, aka dioptin, aka UNR844, aka lipoic acid choline ester.  It's being developed by Novartis for presbyopia.  It works by breaking disulfide bonds which cause the lens to stiffen as we age so that we lose focal accommodation.  It is believed that the formation of these same disulfide bonds also leads to cataracts, so in theory this compound may work for this as well.

 

It's in FDA trials at the moment and I haven't figured out exactly where it is in the process.  Maybe it will pop out as an approved drug you can buy in a few years.  Sigh.

Edited by Daniel Cooper, 22 January 2020 - 08:22 PM.

[Rays]

EV-06, aka dioptin, aka UNR844, aka lipoic acid choline ester.  It's being developed by Novartis for presbyopia.

 

In their Investor Presentation of July 18, 2019, I read that they plan to file UNR844 in 2022. (See link below.) It would be great if we could make the stuff ourselves.

The latest trial ended in December 2019. They plan to publish in ASCRS (ascrs.org).

In Eyeworld magazine of December 2019 there's some discussion about presbyopia eyedrops.

Page 48:

http://digital.eyewo...84-dec-2019/50?

 

 

https://www.novartis...resentation.pdf

[Daniel Cooper]

I got a quote on lipoic acid choline ester and it was crazy expensive.  Something like $6000~$8000/gram.

 

We could try alpha lipoic acid which is of course dirt cheap.

 

 

[smithx]

I thought that in Post # 11 (https://www.longecit...ts/#entry878772) I found enough info to make the rosmarinic acid eye drops you wanted.

 

Was that actually not a good idea after all?

 

 

[NickNick]

Forgot to add.  RA is only slightly soluble in water. It is well soluble in most organic solvents and I believe it can be reasonably soluble in water if the right buffer agent is used.

 

I can't think of many organic solvents that I want to put in my eye, except maybe a very dilute solution of water + DMSO (which has actually been used at least experimentally in the eye in the past).  I suppose you might suspend it in olive oil or castor oil, however I would bet you'd get better permeability into the lens capsule with H20 + buffer or H20 + DMSO.

 

Again, comments from better chemists than I would be appreciated. 

I had the same idea for treating my own cataracts after reading that article. The problem is that they used lenses that have been extracted from cataracts patients. To get the rosmarinic acid to the lens in the eye, it has to pass through several membranes and gel like layer. Some layers are lipophilic some are hydrophilic. Rosmarinic acid is lipophilic. It can be made hydrophilic by dissolving in water with cyclodextrin. This hydrophilic rosmarinic acid will probably only pass through the fist layer, then it might separate from the cyclodextrin, become lipophilic and pass through the next layer. Then it probably won't be able to travel any further. 

 

Have a search for 'cyclodextrin drug delivery eyes'

 

I actually made some eye drops this way and nothing happened. I used a low concentration though because I couldn't find a ph buffer, and I didn't want to irritate my eyes with the ph being too low.

 

It would probably work if the rosmarinic acid could be injected close to the lens. Don't know how we could find someone to do this. 

[NickNick]

Oh heaven no.  The only thing I know is that rosmarinic acid solutions cleared cloudy lens in vitro. I haven't seen an animal or human study.  I don't think anyone's done one yet. I just think I can make a relatively weak rosmarinic acid solution that is very unlikely to be harmful that might help with cataracts.  

 

At this point the only opinion I have is on what doesn't work. From my experience, N-Acetylcarnosine drops don't work (or at least didn't for me) nor did Lanosterol eye drops work.  

 

Rosmarinic acid shows one of the strongest cataract reversal effects in vitro. Whether or not that would translate into an in vivo effect is anyone's guess.  But, when you're trying to reverse or at least delay cataracts, there aren't many games in town.  As long I think it won't hurt me, I'm willing to give it a try.  But what I'm willing to try should have no influence on you.  I'm not a doctor after all.

 

The only other thing out there that is under clinical study is EV-06, aka dioptin, aka UNR844, aka lipoic acid choline ester.  It's being developed by Novartis for presbyopia.  It works by breaking disulfide bonds which cause the lens to stiffen as we age so that we lose focal accommodation.  It is believed that the formation of these same disulfide bonds also leads to cataracts, so in theory this compound may work for this as well.

 

It's in FDA trials at the moment and I haven't figured out exactly where it is in the process.  Maybe it will pop out as an approved drug you can buy in a few years.  Sigh.

I am interested in this as well. It is the reason I don't want cataracts surgery. An artificial lens can't be made flexible enough for focusing, but my natural one might be able to have its flexibility restored with the right drugs.  

 

It would be interesting to know how they are doing the drug delivery. 

 

Another possible new treatment for cataracts, someone (I can't find the article anymore) was using a laser to reverse cataracts. The problem is if you use a search engine to find this study, it just come up with use of lasers in cataracts surgery. They are used to make the incision to remove the lens. I will keep searching and let you know.

[Daniel Cooper]

I thought that in Post # 11 (https://www.longecit...ts/#entry878772) I found enough info to make the rosmarinic acid eye drops you wanted.

 

Was that actually not a good idea after all?

 

 

Just saw this today.  I'm out of the game as I'm getting cataract surgery in a few weeks.  Basically I can tell you what doesn't work.

 

If this were three years ago I'd probably be trying Alpha Lipoic Acid eye drops as a best substitute for Lipoic Acid Choline Ester (LACE) drops.  

 

I think ALA might be useful.  It is both fat and water soluble so it might make it through the capsular bag and into the lens.  Encore Vision decided to develop with LACE on the notion it did a better job of permeating to the lens, but I've seen other papers that contradict that and it may well be that they simply have a better patent claim with LACE.

 

As always, our FDA slows new medical technology development to a crawl.  Not only do I not get to try something that might have slowed the progression or possibly even reversed the cataracts, I am stuck with IOL technology that is at least a decade behind where it should be.  I'm getting monofocal lenses set up for "mini-monovision" when I should be getting a truly accommodative optics or at least a really good Extended Depth of Field IOL.

 

Thanks bunches FDA.

 

Of course, when I get these IOLs placed there's no going back so I'm stuck with what is available in the US as of 2020.  But, I can no longer function with this level of vision so I have no other option.

 

 

 

Edited by Daniel Cooper, 09 March 2020 - 05:07 PM.

[NickNick]

Just saw this today.  I'm out of the game as I'm getting cataract surgery in a few weeks.  Basically I can tell you what doesn't work.

 

If this were three years ago I'd probably be trying Alpha Lipoic Acid eye drops as a best substitute for Lipoic Acid Choline Ester (LACE) drops.  

 

I think ALA might be useful.  It is both fat and water soluble so it might make it through the capsular bag and into the lens.  Encore Vision decided to develop with LACE on the notion it did a better job of permeating to the lens, but I've seen other papers that contradict that and it may well be that they simply have a better patent claim with LACE.

 

As always, our FDA slows new medical technology development to a crawl.  Not only do I not get to try something that might have slowed the progression or possibly even reversed the cataracts, I am stuck with IOL technology that is at least a decade behind where it should be.  I'm getting monofocal lenses set up for "mini-monovision" when I should be getting a truly accommodative optics or at least a really good Extended Depth of Field IOL.

 

Thanks bunches FDA.

 

Of course, when I get these IOLs placed there's no going back so I'm stuck with what is available in the US as of 2020.  But, I can no longer function with this level of vision so I have no other option.

Do you know if the studies with ALA specifically used R-ALA? Common synthetic ALA is a 50/50 mix of 2 enantiomers S-ALA and R-ALA. R-ALA is the one found in nature, but apparently in it's pure form in polymerises at room temperature. If R-ALA is required for eye drops, it sounds quite tricky to get hold of and would need to be stored at low temperature.

[Daniel Cooper]

The study that I read used racemic ALA.  The R enantiomer would be at least a good or twice better.  I'm not sure that you'd need the R enantiomer as it's just breaking disulfide bonds.  It's not being used inside the cell.  But, it certainly isn't going to hurt you.

 

When I was getting ready to do this I purchased R-ALA, but not long after my ophthalmologist did an exam said it was a grade 3 cataract so I went ahead and scheduled surgery.  I think there is little chance that anything I would have access to would reverse a cataract that advanced and at this point my vision is becoming non-functional. 

 

 

 

 

[NickNick]

The study that I read used racemic ALA.  The R enantiomer would be at least a good or twice better.  I'm not sure that you'd need the R enantiomer as it's just breaking disulfide bonds.  It's not being used inside the cell.  But, it certainly isn't going to hurt you.

 

When I was getting ready to do this I purchased R-ALA, but not long after my ophthalmologist did an exam said it was a grade 3 cataract so I went ahead and scheduled surgery.  I think there is little chance that anything I would have access to would reverse a cataract that advanced and at this point my vision is becoming non-functional. 

I am interested to know about R-ALA. I found a supplier in China but I don't know if R-ALA is stable as a powder. What is your experience with it, did you buy it as a powder? 

[Daniel Cooper]

I am interested to know about R-ALA. I found a supplier in China but I don't know if R-ALA is stable as a powder. What is your experience with it, did you buy it as a powder? 

 

I wouldn't even begin to consider buying R-ALA from a direct supplier in China when I can get it from any number of reasonably reputable vendors.  A number of well know supplement makers sell it in capsule form and Bulk Supplements sells it in powder form starting at 10g quantities and going up.  If you want to make eye drops out of it, 10g is going to last you a long time.  For eye drops I would definitely start with bulk powder as I assume that capsules are going to have fillers and excipients which you don't want in your eye.

 

To me, buying off Alibaba is a last resort.