691 replies to this topic

[Logic]

Progress report, plans and thoughts on this group buy:

 

I have been gathering quotes on Nilotinib Hydrochloride Monohydrate, as used in the Parkinson's study.

 

Prices are in the region of $6000 for a minimum of 500 grams.
ie: $ 12.00 / gram = $ 54.00 - $ 108.00 per month at 150 - 300 mg per day.

 

I want to add the cost of 3rd party analysis to the Group Buy before it even starts and pay via an escrow account, pending the satisfactory outcome of this analysis.

(Escrow companies are trusted, registered companies that hold the payment on behalf of the buyer and seller until a certain condition is met.  

In this case; the Nilotinib passing a Mass Spectrometry purity test successfully.

They also settle any disputes that may arise.

Costs seems to be in the region of $ 163.00 = ~ $20 per person atm)

https://www.escrow.com/

 

I have found Tandem Mass Spectrometry data for Nilotinib, probably making the acquisition of a known sample unnecessary and will report back once this is confirmed to be usable.  

 

I am getting advice on testing from K. Moody of Ichor Therapeutics who is doing the 'Free C60oo quality control' tests as well as cancer and lifespan studies with C60oo:

http://www.longecity...r-therapeutics/

As K. Moody does not have  a Mass Spectrometry machine, the lab that will be used is still undecided.

If you have any suggestions as to this; plz post.

 

I am also looking at using a drop shipper to aliquot, package and ship Nilotinib as I am in South Africa where the postal service is ...unpredictable and shipping to and from somewhere so far away from most parties would  add to the cost unnecessarily.

Finding one thats reliable and deals with meds seems impossible!?
So I may have to find members in the different countries, willing to do this.
Please post if you are willing to help with aliquoting, packaging and shipping Nilotinib in your country.

 

Nilotinib is a powerful anti cancer drug that can cause sudden death in very rare cases and should not be taken lightly.
Please read the various warnings and recommendations before taking this or giving it to someone you know with Parkinson's:
http://hcp.novartis....roducts/tasigna
http://www.tasigna.c...-of-product.pdf
https://www.novartis...rtfolio/tasigna

 

People who have expressed interest in this group buy so far:

( Including Escrow costs, Excluding shipping and testing costs)

 

resveratrol_guy            - 100 g     = $ 1 220.00 
Der Springende Punkt  - 75 g       = $ 920.00 
LongLife                       - 100 g     = $ 1220.00
themadscientist            - 50 g       = $ 620.00
rikelme                         - 50 g       = $ 620.00
ceridwen                      - 100 g     = $ 1220.00
geo12the                     - ??? g     = $ ???
roydeman                    - 50-100g = $ 620.00 - 1220.00
Logic                           - 30 g        = $ 380.00 
                                     ________
                                     555-605 + g

 

Please post or PM me the country to which you would like your Nilotinib sent if you are still interested at this new price for Nilotinib Hydrochloride Monohydrate, as used in the Parkinson's study people.

 

Assuming everyone is still interested at:
$ 12.00 / gram = $ 54.00 - $ 108.00 per month at 150 - 300 mg per day + Escrow + testing + Shipping
We have enough people to set the ball rolling!

Edited by Logic, 13 January 2016 - 03:01 PM.

[ceridwen]

I've changed my mind. I really don't have that much money. Willing to settle for 30mg instead. Really sorry about that

[Logic]

I've changed my mind. I really don't have that much money. Willing to settle for 30mg instead. Really sorry about that

 

That's fine ceridwen.  
As the price for the Nilotinib Hydrochloride Monohydrate as used in the Parkinson's study is higher; one can't expect the people who committed at Noot in the sky's lower price to stay so.

I assume you mean 30 grams and not milligrams though?
That is still over 6 months worth at 150 mg per day and I wouldn't even take it that often in your case.

[themadscientist]

I wasn't expecting it to be that much. At this moment in time, 20 grams is all I can afford. 

[ceridwen]

Yes I'll just take it when I have difficulty talking and walking basic stuff like that.

[deetown]

In for 20 grams

 

[Logic]

I am having more trouble than I expected finding a lab that will test the Nilotinib even though it's not a controlled substance and:
 

Products currently covered by valid US Patents can be bought for R&D use in accordance with 35 USC 271(e) +A13(1).

Any patent infringement and resulting liability is solely at buyer risk.

If anyone here knows of a reputable lab that will test N for a reasonable price please post.

Also plz go and vote to have group buy substances tested through Longecity here:
http://www.longecity...ments-programe/

 

I get the impression that those that do know of labs make money out of selling supps etc and don't want to share what they consider to be their IP, or want the above Longecity initiative to succeed!?  

[resveratrol_guy]

Wait a sec... why are we aliquotting? Wouldn't it be cheaper and just more convenient to pill pack?

Edited by resveratrol_guy, 22 January 2016 - 01:42 AM.

[LongLife]

LOGIC:

 

The price is more than double what we were seeing earlier. I will not be able to afford this at $12/gram, as much as I would like to have a try with it. Also the death rate is a concern, as I have not found anyone willing to give it a try...who has Parkinson...even though they know the end product of Parkinson; death.

[resveratrol_guy]

Death rate? Do we really have a good handle on that? From Logic's posts, it sounds like there are isolated reports of heart failure in very unhealthy individuals, but after all, as you said, the alternative is death by Parkinson's. My impression is that the risk/reward ratio for Parkinson's patients with reasonable cardiac function is skewed in their favor. But I admit that the numbers are hard to gather here.

[ceridwen]

Think I want to go for 12 too. It really is very expensive

[Logic]

LOGIC:

 

The price is more than double what we were seeing earlier. I will not be able to afford this at $12/gram, as much as I would like to have a try with it. Also the death rate is a concern, as I have not found anyone willing to give it a try...who has Parkinson...even though they know the end product of Parkinson; death.

 

Noot got a quote on Nilotinib.  I got a quote on Nilotinib Hydrochloride Monohydrate, as used in the Parkinson's study Longlife.
I have subsequently found other labs selling it and will hopefully be able to get a better price with some haggling, but 1st I need to organise a lab to test the product.

This is proving difficult as it seems my 'New South African ...brothers' have stolen the copper phone lines again, leaving me without internet. I am currently typing this on a friend in a different suburb's computer.

 

Paying via escrow account pending the success of said testing also adds to the cost, but at least you get your money back, minus about $20 if its not as advertised.

 

Note that the standard, Novartis  price works out at around  $ 416 per gram..!    

 

I will get on this again when I am online again.

SOZ for the delay.

[Logic]

Soz for the long delay:

Between the spotty internet connectivity here and labs running for the hills when Nilotinib, not from Novartis and to be used in humans is mentioned; I thought that my vision of a proper group buy was dead in the water.

Fortunately; due to some.. carefully worded Emails, Labs have been getting back to me and things are progressing well again:

 

This is the most probable synthetic method used for Nilotinib's production:

http://www.google.co...tents/US9061028

 

A read through of the patent in search of solvents and heavy metals used in Nilotinib's production and  likely to be left the substance, yielded:

• thionyl chloride (dangerous/toxic)
• propyl phosphonic anhydride (may be used. toxic)
• Cyanamide (moderately toxic)
• stannous chloride (ok)
• n-butanol (ok)
• chloroform (ok)

These are the substances that will be tested for.

 

The required tests; in order of importance are:

• Tandem MS, will identify N as N and show up any serious discrepancies and contaminants.
• HPLC with a UV detector to look for traces of the most common and dangerous (residual) solvents etc, as gleaned from the patent above.
• Heavy metal testing is not needed for synthetic substances.

The substance should pass the USP standard for drug products:
http://www.usp.org/s...c232-usp-39.pdf

before our funds are released from an escrow account to the manufacturer.

 

I am currently discussing the required tests with a number of labs and expect to receive quotes before the end of the week.

My thanks to Niner and K. Moody for their advice with the above.

 

 

Finding a reliable and properly registered and accredited and reasonably priced escrow service is also taking some doing due to every scammer and his mother putting up fake escrow service sites lately.  It seems to be the latest craze!  

I am doing the above checks and whittling down the list and have begun talking to some services regarding accepting funds from multiple buyers.

 

All this has/is taking longer than anticipated, due to the nature of the product (IP issues etc) and the fact that I intend to see this group buy to proceed without the chaos and mud slinging that usually occurs.

 

I hope to post another update soon.

 

[resveratrol_guy]

Soz for the long delay:

Between the spotty internet connectivity here and labs running for the hills when Nilotinib, not from Novartis and to be used in humans is mentioned; I thought that my vision of a proper group buy was dead in the water.

Fortunately; due to some.. carefully worded Emails, Labs have been getting back to me and things are progressing well again:

 

This is the most probable synthetic method used for Nilotinib's production:

http://www.google.co...tents/US9061028

 

A read through of the patent in search of solvents and heavy metals used in Nilotinib's production and  likely to be left the substance, yielded:

• thionyl chloride (dangerous/toxic)
• propyl phosphonic anhydride (may be used. toxic)
• Cyanamide (moderately toxic)
• stannous chloride (ok)
• n-butanol (ok)
• chloroform (ok)

These are the substances that will be tested for.

 

The required tests; in order of importance are:

• Tandem MS, will identify N as N and show up any serious discrepancies and contaminants.
• HPLC with a UV detector to look for traces of the most common and dangerous (residual) solvents etc, as gleaned from the patent above.
• Heavy metal testing is not needed for synthetic substances.

The substance should pass the USP standard for drug products:
http://www.usp.org/s...c232-usp-39.pdf

before our funds are released from an escrow account to the manufacturer.

 

I am currently discussing the required tests with a number of labs and expect to receive quotes before the end of the week.

My thanks to Niner and K. Moody for their advice with the above.

 

 

Finding a reliable and properly registered and accredited and reasonably priced escrow service is also taking some doing due to every scammer and his mother putting up fake escrow service sites lately.  It seems to be the latest craze!  

I am doing the above checks and whittling down the list and have begun talking to some services regarding accepting funds from multiple buyers.

 

All this has/is taking longer than anticipated, due to the nature of the product (IP issues etc) and the fact that I intend to see this group buy to proceed without the chaos and mud slinging that usually occurs.

 

I hope to post another update soon.

 

Nice work. Your proposed list of substances to test sounds reasonable.
 

[involuted]

Pharmacology noob here. What exactly is the mechanism of action of this drug?

 

[resveratrol_guy]

Pharmacology noob here. What exactly is the mechanism of action of this drug?

 

It upregulates autophagy within neurons and other cells. In high doses, this effectively causes the cell to digest itself, hence its applicability to tumor destruction. In lower doses with chronic delivery, it seems capable of dissolving the alpha synuclein plaque which underlies Parkinson's, Lewy body dementia, and to some extent Huntington's.
 

Macroautophagy, however, is not upregulated, meaning that plaque in the intercellular matrix is likely unaffected. For that, at least in the brain, we need to activate the microglia. I don't know of any easy way to do this, although various Alzheimer's vaccine candidates are attempting to do so. The drug GMCSF is probably the most promising candidate we have, although it's prohibitively expensive; oddly enough, contracting rheumatoid arthritis may release GMCSF endogenously, leading to protection against dementia, as discussed in the forums here. Meanwhile BioViva hypothesizes that its proposed TERT therapy for Alzheimer's prevention will activate the microglia and thereby reduce these extracellular protein aggregates. In a word, we don't have a financially and biologically viable therapy yet.

 

[ceridwen]

No more than 1g it's so expensive

[Logic]

 

Pharmacology noob here. What exactly is the mechanism of action of this drug?

 

It upregulates autophagy within neurons and other cells. In high doses, this effectively causes the cell to digest itself, hence its applicability to tumor destruction. In lower doses with chronic delivery, it seems capable of dissolving the alpha synuclein plaque which underlies Parkinson's, Lewy body dementia, and to some extent Huntington's.
 

Macroautophagy, however, is not upregulated, meaning that plaque in the intercellular matrix is likely unaffected. For that, at least in the brain, we need to activate the microglia. I don't know of any easy way to do this, although various Alzheimer's vaccine candidates are attempting to do so. The drug GMCSF is probably the most promising candidate we have, although it's prohibitively expensive; oddly enough, contracting rheumatoid arthritis may release GMCSF endogenously, leading to protection against dementia, as discussed in the forums here. Meanwhile BioViva hypothesizes that its proposed TERT therapy for Alzheimer's prevention will activate the microglia and thereby reduce these extracellular protein aggregates. In a word, we don't have a financially and biologically viable therapy yet.

 

 

Quite so.  Thx RG.  

I would like to add that the reason for my, and our, great interest in this substance is due to the miraculous effect Nilotinib had on Parkinson's sufferers.

Those tested went from being rigid and bedridden to talking and getting up and going to the kitchen to make themselves something to eat etc!

IIRC there was only one lady withdrawn from the study...  By her husband.  He preferred her being unable to speak!  

 

You will find links to the pilot study a page or 2 back.

 

It seems to be most effective for those with Lewy Body dementia.  whose symptoms are like a combo of parkinson's and Alzheimer's.

 

There are other, less drastic ways to upregulate PARKIN and thus auto/microphagy that. more conservative, healthy individuals can try as a means of preventing dementia,  but if you have parkinson's or Lewy Body dementia;  Nilotinib is your best bet by far atm.

Edited by Logic, 04 February 2016 - 07:34 AM.

[Logic]

No more than 1g it's so expensive

 

Yes it is expensive ceridwen  :(

But a hell of a lot cheaper than Novartis's price.
I will haggle with the different labs a bit, but don't them them cutting corners in its production and thus quality.
I am also hoping that one of the cheaper escrow services pan out.

 

I would say that at 150 mg per day; 4,5 grams (= a 1 month supply) would be the minimum to consider.

You may well see effects from 6 or 7 doses, but don't recall a timeframe for effects to be seen mentioned anywhere.

 

http://www.dailymail...ancer-drug.html

Mentions 6 months, but that was for advanced stage Parkinson's sufferers.

As you are unsure of the reason/s for your mental decline; perhaps you might find Sarcosine interesting:
http://www.longecity...ine-users-read/

http://www.longecity...-schizophrenia/

http://www.longecity...tor-co-agonist/

Edited by Logic, 04 February 2016 - 08:07 AM.

[csimon02]

Interested. Not sure how much I would be in for, but definitely interested.

[csimon02]

Did the Georgetown study reveal how many milligrams the patients were given?

[Logic]

Did the Georgetown study reveal how many milligrams the patients were given?

 

150 - 300 mg per day.

About half the dosage used for cancer, which apparently resulted in there being no side effects from N.

Apparently..? 

[stefan_001]

Anybody any idea whether this would it through customs in Europe?

Logic are you planning to simply send it be mail? I am somewhat intrigued although my brain is fine.... But there maybe not so many chances to get some either for myself or family. Any ideas on shell life?

[Logic]

The different crystalline Forms A, B, C and amorphous have been characterized. Form A corresponds to a dihydrate form. Form B and Form C are monohydrate forms obtained after desolvation of different solvates.  Form B, isolated from the synthetic process and used in the medicinal product, is the most stable form. It shows the least hygroscopic behaviour of all the three crystalline forms A, B, and C. No transformation was observed after storing these three forms at room temperature even for several months

 

All batches have been placed on long term testing at 25°C/60% RH and 30°C/75% RH, accelerated testing at 40°C/75% RH, as well as testing at other temperatures (e.g. -20°C, 5°C and 50°C) and special tests (e.g. photostability and microbial limit tests). Up to 12 months of stability data for the pilot batches and up to 6 months for the full scale production batches are presented in this application. Batches stored in the three different blister packaging but data were presented only for two of them. Parameters investigated: Assay, degradation products, appearance, mean mass, dissolution and microbiological purity.

 

No change for the chemical results has been observed over 3 months at 50°C. Regarding the physical data, no change has been observed for the appearance and the mean mass.

 

http://www.ema.europ...WC500034398.pdf

 

We are getting the less hygroscopic (the ability of a material to absorb humidity from the air) monohydrate form

I would add a silica gel packet to the container and store it in a cool dry place.

The problem with storing stuff in the freezer is that when you take it out and open it; the low temperature attracts/condenses water from the air onto the cold surface/substance.

 

As Nilotinib is something that Parkinson's sufferers have to take for life; I intend to do a group buy once every 1-3 months, so no reason to stock up.

Also prices should drop as trust is built with the supplier and the need for escrow services and testing abates.

 

I am busy vetting escrow services atm.

 

[stefan_001]

Thanks for that info, appreciated. I will keep following with interest.

Edited by stefan_001, 07 February 2016 - 03:35 PM.

[csimon02]

In for 50g.

 

Thanks for doing this.

[geo12the]

If someone had a genetic predisposition to Parkinson's (my husband does- an LRRK2 GtoS mutation) but is asymptomatic what would be a reasonable  prophylactic dose regime? Could a low dose (25 or 50 mg/day) be sufficient for a prophylactic effect?

 

I am in for 25g

 

 

[Logic]

If someone had a genetic predisposition to Parkinson's (my husband does- an LRRK2 GtoS mutation) but is asymptomatic what would be a reasonable  prophylactic dose regime? Could a low dose (25 or 50 mg/day) be sufficient for a prophylactic effect?

 

I am in for 25g

 

This is a question on a lot of minds I think geo12the.

I have looked into it some; without any luck so far.

There are no response graphs form the parkinson's study as everybody got either 150 or 300 mg by the looks of it.  It may have been doses between 150 & 300 mg. but still no dosage response curves I can find.    

 

I will recommend starting with small doses and working your way up, so there will be anecdotal reports of immediate/ish, noticeable effects soon.

(The chinese new year has interrupted negotiations around escrow payment atm.  Where have I heard that before!?    )

 

I also plan to recommend a number of steps to be taken before starting as well as a way to boost the clearance of N if one's pulse becomes irregular.

N is not aspirin..!

 

I have found a number of things that are safer than N that one could try, but how would one know if they are working before the onset of the disease..?

[Logic]

Macroautophagy, however, is not upregulated, meaning that plaque in the intercellular matrix is likely unaffected. For that, at least in the brain, we need to activate the microglia. I don't know of any easy way to do this, although various Alzheimer's vaccine candidates are attempting to do so. The drug GMCSF is probably the most promising candidate we have, although it's prohibitively expensive; oddly enough, contracting rheumatoid arthritis may release GMCSF endogenously, leading to protection against dementia, as discussed in the forums here. Meanwhile BioViva hypothesizes that its proposed TERT therapy for Alzheimer's prevention will activate the microglia and thereby reduce these extracellular protein aggregates. In a word, we don't have a financially and biologically viable therapy yet.

 

 

Thx RG

 

You may find some leads, or at least some prophylactics here:

http://biofoundations.org/?p=4107

[Logic]

Progress report:

 

I am afraid that my plans for the perfect group buy, using an escrow account for payment and a drop shipper are not going to work out.
I am proposing changing the plan to a normal buy with the assistance of members for local shipping:

 

Escrow just won't work for us:

 

After much negotiating it is evident that none of the legitemate Escrow services, except escrow.com will accept payments via Paypal for some reason.

But Escrow.com:

• Refuses to accept payments from multiple parties.
• Has hidden egregious fees (disbursement etc) that are 'hidden' elsewhere on their site:

Their fee calculator page calculates gave the fee on a $6000 transaction as $ 165.10

But further down on the page:

• "Transactions with a Buyer outside the United States will be charged an additional $25.00"

Elsewhere on the site (ie: not even on the fees page):

• "Credit card and PayPal payments are accepted only for Premier Service level...and are subject to Escrow.com approval."

Now the 'premier service' is not charged @ 3.25% but 6.3%..!

 

Further research uncovered the fact that Escrow.com has been bought by Matt Barrie of freelancer.com, which has less than flattering reviews on the internet!
https://omnipresentw...com-complaints/

 

In Summary:

IMHO the only escrow service that may have worked has  egregious, hidden fees that we would be obliged to pay once they had received the initial 'hook amount' from us, making me 'as popular as baked beans on a bus trip' if we had taken that route on my recommendation!

 

The manufacturers I have received quotes from, on the other hand, do seem to have pretty good reputations on Longecity and elsewhere.
So I now propose we go with a normal buy and just send the whole package to the lab (in America) to be tested.
If the lab discovers that the Nilotinib is unfit for our consumption due to residual solvents etc; they will be able to purify it further by a process called recrystallization.
This will mean an additional cost, but at least we won't have lost all our money.

Shipping:

There just aren't any drop shippers that will aliquot and ship medications.

Most all 'drop shippers' have their own product line consisting of knockoffs and dildos etc, where you essentially sign up to be a salesman for them, at your cost..!
ie:  It was a huge waste of my time to even look.

 

I have arranged to have the Nilotinib shipped as far as the lab in Baltimore.
I hope that someone close to Baltimore can then receive the package divide it up and package it properly, and then post off the Nilotinib to everyone for an appropriate small fee?

This packaging and shipping fee would depend on the container that the chosen person chose to use and on the distance that the parcel had to go.

This still has to be worked worked out and is not included in the cost below, but it looks to be about $20.

(I can do this myself, except I am far away from everyone here in South Africa, which would add to cost, and the postal system here is ...'unreliable' nowadays.

There are one or two respected, qualified moderators I will approach about doing us this favour, if no-one in the group buy is keen or agreeable to everyone.)

Cost:
I have managed to negotiate a small discount with the manufacturer, but dont think its a good idea to 'push it' as they may then cut corners in their manufacturing process to lower their costs.

 

The cost of the 500 grams of stable Nilotinib Hydrochloride Monohydrate, as used in the Parkinson's study, should remain at $ 6000 IMHO.

But this now includes shipping to the lab in America, plus $100? for the shipper/packager and packaging.

ie: A cost of $ 12.00 / gram = $ 54.00 - $ 108.00 per month at 150 - 300 mg per day.
Plus ~$ 70 for testing and shipping.

The cost of the lab tests is $ 600 for LC-MS, LC-MS/MS and GC-MS.

That cost will be shared evenly between the members of the group buy, so the more members the better. 

ie:  If you know anyone who might be interested; put on you salesman hat!  
I will look for appropriate threads to post in too.

So far the following people are interested:

 

Person                            # of grams    Price USD    Testing and shipping
resveratrol_guy              100 g            1200             ~70
LongLife                         100 g            1200             ~70
themadscientist              20 g              240               ~70
rikelme                           50 g              600                ~70
ceridwen                        30 g ?           360 ?             ~70
roydeman                      50-100g        600 - 1200     ~70
Logic                              30 g              360                ~70
deetown                         20 g              240                ~70 
geo12the                       25 g              300                ~70
csimon02                       50 g              600                ~70
stefan_001                    ?? g               ???                ~70

 

That works out to 550 - 600 grams excluding stefan_001

 

People please confirm:

• That you are happy with the above so far (hopefully   ) by posting here again.
• Add your country for shipping cost calculations.

Please let us know if you are willing to receive the package divide it up and package it properly, and then post off the Nilotinib to everyone for an appropriate small fee? (Preferably someone close to Baltimore)