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What is the TA Sciences TA-65 molecule ?

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jc101

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Sep 28, 2007, 2:22:34 PM9/28/07
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Wondering if the active TA-65 in the TA Sciences product is a
manufactured chemical, cycloastrogenol, made as described in their
patent app from astragaloside IV in the concentrated astragalus
extract :

COMPOSITIONS AND METHODS FOR INCREASING TELOMERASE ACTIVITY
http://v3.espacenet.com/textdes?DB=EPODOC&IDX=KR20060034237&F=0&QPN=KR20060034237
or http://tinyurl.com/29pswy

>From this patent app "Astragaloside IV (designated herein as (1) was
also obtained by the present authors from Ai Chunmei, Chengdu 610041,
P. R. China. Cycloastragenol (2) can be prepared by treatment of
astragaloside IV (1) with methanolic HCl, followed by neutralization,
standard workup, and purification by chromatography..."
--------------
It bothered me that none of TA-65 was found in other astragalus and
astragalus extract samples at limit of detection of 1 ppm even though
TA-65 is supposed to be a "naturally occurring molecule"
http://www.tasciences.com/pdf/dalton_pharma_01.pdf

"...There the base material is further processed to yield the single
TA-65 molecule...." from http://tinyurl.com/358gna

So I maybe this is an acid process in methanol where the astragaloside
molecule is converted to cycloastragenol - a common ring closing
reaction. If so, this is why none of the commercial samples from other
vendors showed any TA-65, it also would mean that this is a
synthesized rather than extracted molecule, thus illegal to sell as a
dietary supplement, actually it would be an unapproved new drug.

Probably why they have to have a physician prescribe it in their
"Patton Protocol". Wonder if their physician is aware that this would
constitute prescription of an unapproved new drug, if TA-65 were
actually cycloastragenol ?
-----------------
At any rate, the naturally occuring astragaloside IV molecule is less
potent than the cycloastragenol. The patent app above shows the
relative potency vis telomerase for all of these molecules, so should
be able to expect equal results from the other astragalus extract
molecules (dosed equivalently per the patent app relative potency to
equal the 5 mg TA-65 dosage effect). Their clinical results should be
repeatable for the rest of us using this equivalency as shown in the
patent application.

>From the patent app " .... cycloastragenol is administered at a
level of at least 1 mg/day, preferably at least 5 mg/day; or the
compound designated herein as astragaloside IV is administered at a
level of at least 50 mg/day, preferably at least 100 mg/day."
--------------------
I think of no other explanation for the absence of TA-65 in other
astragalus samples. There would only naturally be a tiny miniscule
undetectable amount of cycloastragenol in Astragalus naturally,
without acid processing to convert the astragalosides to the cyclo-
ring compounds.
-----------------------------
Here is the simple synthesis and data for cycloastragenol from the
patent app:
" Example 1. Conversion of astragaloside IV(1) to cycloastragenol(2)
To astragaloside IV (1) (5.00 g, mmol) was added"HCl-MeOH 10" (TCI
America) (500 mL) and the mixture was stirred at room temperature for
7 days. The reaction mixture was concentrated to about half volume
under reduced pressure at 20 C (do not heat). The mixture was
partitioned into aqueous sodium bicarbonate and ethyl acetate.

The aqueous layer was extracted with ethyl acetate again. The organic
layers were combined, washed with saturated sodium chloride, dried on
anhydrous sodium sulfate, and concentrated under reduced pressure. The
residue was purified by column chromatography (20:1-14 : 1 chloroform/
methanol). In order to replace the residual solvent with ethanol, the
purified material was dissolved in ethanol and the solvent was removed
under reduced pressure to afford 2 (2.1 g, 64%).

1H NMR (CDCl3) # (ppm) 0. 34 (d, J= 4.7 Hz, 1H), 0. 48 (d, J= 4.3 Hz,
1H), 0.92 (s, 3H), 0.93 (s, 3H), 1.0-1. 8 (m, 13H), 1.11 (s, 3H), 1.
19 (s, 3H), 1.22 (s, 6H), 1.27 (s, 3H), 1.9-2. 0 (m, 4H), 2.30 (d, J=
7.8 Hz, 1H), 2.54 (q, J= 11.8 Hz, 1H), 3.27 (m, 1H), 3.50 (m, 1H),
3.72 (t, J= 7.4 Hz, 1H), 4.65 (q, J= 7.4 Hz, 1H). ESI-MS m/z Positive
491 (M+H)+, Negative 549 (M+AcO)'. TLC (Merck, Kieselgel 60) Rf = 0.33
(6: 1 chloroform/methanol "
----------------
Feel free to cross post this.
-----------------
JLC

Paul Antonik Wakfer

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Sep 29, 2007, 11:26:06 PM9/29/07
to
On Sep 28, 2:22 pm, jc101 <uniqueprodu...@comcast.net> wrote:
> Wondering if the active TA-65 in the TA Sciences product is a
> manufactured chemical, cycloastrogenol, made as described in their
> patent app from astragaloside IV in the concentrated astragalus
> extract :

[snip detail]

> I think of no other explanation for the absence of TA-65 in other
> astragalus samples. There would only naturally be a tiny miniscule
> undetectable amount of cycloastragenol in Astragalus naturally,
> without acid processing to convert the astragalosides to the cyclo-
> ring compounds.

There is no question that cycloastragenol does exist within naturally
occurring astralagus root (whether it is lost in some/most/all
extracting processes, or at least not concentrated, is another
question).
http://tinyurl.com/2mkmla

I think that the contract manufacturer for TA Sciences is effectively
"enhancing" this natural occurrence by their processing methods (by a
mechanism as you have described). Since cycloastragenol does occur
naturally, I do not think this would be classified as a manufactured
drug any more than, for example, making synthetic vitamin C rather
then extracting it from plant sources is classified as drug
manufacturing.

Therefore, I think that all someone needs to do is perfect the same
process as you have described and they will have cycloastragenol which
they can sell openly on the market.
I have been waiting patiently for many months now to see some
supplement company bring out a high potency astragaloside IV product.
There are many Chinese sources of up to 99% purity available and a
few other non-Chinese sources - one is Dalton Pharma -
http://dalton.com/astragaloside.htm - the same company that did the
testing to which you referred and is likely the contract manufacturer
of TA-65, IMO. Therefore, it should be easy enough for some other
manufacturer to start with a highly pure astragaloside IV and end up
with a TA-65 knock-off for sale at a much lower price.

If it is well done and adequately tested, I will be one of the first
buyers, and I know several others who would also grab the chance.

Who wants to do it first?

--Paul Wakfer

MoreLife for the rational - http://morelife.org
Reality based tools for more life in quantity and quality
The Self-Sovereign Individual Project - http://selfsip.org
Self-sovereignty, rational pursuit of optimal lifetime happiness,
individual responsibility, social preferencing & social contracting

jc101

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Sep 30, 2007, 7:56:13 PM9/30/07
to
On Sep 29, 10:26 pm, Paul Antonik Wakfer <p...@morelife.org> wrote:
> On Sep 28, 2:22 pm, jc101 <uniqueprodu...@comcast.net> wrote:
>
> > Wondering if the active TA-65 in the TA Sciences product is a
> > manufactured chemical, cycloastrogenol, made as described in their
> > patent app from astragaloside IV in the concentrated astragalus
> > extract :
>
> [snip detail]
>
> > I think of no other explanation for the absence of TA-65 in other
> > astragalus samples. There would only naturally be a tiny miniscule
> > undetectable amount of cycloastragenol in Astragalus naturally,
> > without acid processing to convert the astragalosides to the cyclo-
> > ring compounds.
>
> There is no question that cycloastragenol does exist within naturally
> occurring astralagus root (whether it is lost in some/most/all
> extracting processes, or at least not concentrated, is another
> question).http://tinyurl.com/2mkmla

>
> I think that the contract manufacturer for TA Sciences is effectively
> "enhancing" this natural occurrence by their processing methods (by a
> mechanism as you have described). Since cycloastragenol does occur
> naturally, I do not think this would be classified as a manufactured
> drug any more than, for example, making synthetic vitamin C rather
> then extracting it from plant sources is classified as drug
> manufacturing.
>
> Therefore, I think that all someone needs to do is perfect the same
> process as you have described and they will have cycloastragenol which
> they can sell openly on the market.
> I have been waiting patiently for many months now to see some
> supplement company bring out a high potency astragaloside IV product.
> There are many Chinese sources of up to 99% purity available and a
> few other non-Chinese sources - one is Dalton Pharma -http://dalton.com/astragaloside.htm- the same company that did the

> testing to which you referred and is likely the contract manufacturer
> of TA-65, IMO. Therefore, it should be easy enough for some other
> manufacturer to start with a highly pure astragaloside IV and end up
> with a TA-65 knock-off for sale at a much lower price.
>
> If it is well done and adequately tested, I will be one of the first
> buyers, and I know several others who would also grab the chance.
>
> Who wants to do it first?
>
> --Paul Wakfer
>
> MoreLife for the rational -http://morelife.org

> Reality based tools for more life in quantity and quality
> The Self-Sovereign Individual Project -http://selfsip.org

> Self-sovereignty, rational pursuit of optimal lifetime happiness,
> individual responsibility, social preferencing & social contracting

Synthetic Vitamin C is not an apt analogy as vitamins are expressly
allowed under DSHEA http://www.cfsan.fda.gov/~dms/dietsupp.html
regardless of whether synthetic or natural. Astragalosides extracted
from plant material would be allowed as "constituents" or "extracts"
or "concentrates" by the same regulation.

However, if a concentrated astragaloside extract were chemically
processed with acid to make synthetic cycloastragenol, is that
allowable just because there exists an extremely minute amount of
cycloastragenol in the original plant ? I tend to think not. It is not
an extract nor a concentrate any longer after chemical synthesis. Is
it a "constituent" ? Not if it wasn't cycloastragenol in the plant to
start with. If this were the case, then any naturally occurring
molecule in any plant could be synthesized and sold as a "dietary
supplement." Big risk to a marketer.

The matter is academic as far as practical usage. It will always be
less expensive to just use 10x or 20x as much of the astragaloside IV.
It is effective clearly from the patent application http://tinyurl.com/29pswy
. Similar to just using twice as much cheap 50% resveratrol knotweed
extract, rather than very expensive synthetic resveratrol. Effects are
the same, costs way less to double up on the natural product. So, just
use 100 mg astragaloside IV, that should be plenty to equal 5 mg
TA-65. Or cheaper yet, 500 mg of a 20% astragaloside IV extract.

Shouldn't confuse % purity with the usefulness of the product. If it
is weaker, just take more of it. You just have to check each lot
against a standard at a lab to see just how much astragaloside IV is
actually present, as this varies, and the claims of the Chinese mfg
cannot be trusted.

If anyone has some links to astragaloside IV extract sources, pls
post..

I tend to think this treatment of the telomeres is far too early and
risky for anyone who is not over 65 or 70 years old, when fast rate of
cell loss due to telomere insufficiency ensues.

If someone had a TA-65 capsule, they could check the peaks against the
cycloastragenol standard and see for sure what is in it.
JLC

rj...@my-deja.com

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Oct 4, 2007, 5:31:53 PM10/4/07
to
> > few other non-Chinese sources - one is Dalton Pharma -http://dalton.com/astragaloside.htm-the same company that did the

> > testing to which you referred and is likely the contract manufacturer
> > of TA-65, IMO. Therefore, it should be easy enough for some other
> > manufacturer to start with a highly pure astragaloside IV and end up
> > with a TA-65 knock-off for sale at a much lower price.
>
> > If it is well done and adequately tested, I will be one of the first
> > buyers, and I know several others who would also grab the chance.
>
> > Who wants to do it first?
>
> > --Paul Wakfer
>
> > MoreLife for the rational -http://morelife.org
> > Reality based tools for more life in quantity and quality
> > The Self-Sovereign Individual Project -http://selfsip.org
> > Self-sovereignty, rational pursuit of optimal lifetime happiness,
> > individual responsibility, social preferencing & social contracting
>
> Synthetic Vitamin C is not an apt analogy as vitamins are expressly
> allowed under DSHEAhttp://www.cfsan.fda.gov/~dms/dietsupp.html

> regardless of whether synthetic or natural. Astragalosides extracted
> from plant material would be allowed as "constituents" or "extracts"
> or "concentrates" by the same regulation.
>
> However, if a concentrated astragaloside extract were chemically
> processed with acid to make synthetic cycloastragenol, is that
> allowable just because there exists an extremely minute amount of
> cycloastragenol in the original plant ? I tend to think not. It is not
> an extract nor a concentrate any longer after chemical synthesis. Is
> it a "constituent" ? Not if it wasn't cycloastragenol in the plant to
> start with. If this were the case, then any naturally occurring
> molecule in any plant could be synthesized and sold as a "dietary
> supplement." Big risk to a marketer.
>
> The matter is academic as far as practical usage. It will always be
> less expensive to just use 10x or 20x as much of the astragaloside IV.
> It is effective clearly from the patent applicationhttp://tinyurl.com/29pswy

> . Similar to just using twice as much cheap 50% resveratrol knotweed
> extract, rather than very expensive synthetic resveratrol. Effects are
> the same, costs way less to double up on the natural product. So, just
> use 100 mg astragaloside IV, that should be plenty to equal 5 mg
> TA-65. Or cheaper yet, 500 mg of a 20% astragaloside IV extract.
>
> Shouldn't confuse % purity with the usefulness of the product. If it
> is weaker, just take more of it. You just have to check each lot
> against a standard at a lab to see just how much astragaloside IV is
> actually present, as this varies, and the claims of the Chinese mfg
> cannot be trusted.
>
> If anyone has some links to astragaloside IV extract sources, pls
> post..
>
> I tend to think this treatment of the telomeres is far too early and
> risky for anyone who is not over 65 or 70 years old, when fast rate of
> cell loss due to telomere insufficiency ensues.
>
> If someone had a TA-65 capsule, they could check the peaks against the
> cycloastragenol standard and see for sure what is in it.
> JLC

>From the patent app " .... cycloastragenol is administered at a


level of at least 1 mg/day, preferably at least 5 mg/day; or the
compound designated herein as astragaloside IV is administered at a
level of at least 50 mg/day, preferably at least 100 mg/day."

Thus it seems 50 mg astragaloside IV is equipotent to 1 mg of
cycloastragenol. I think this will remain a less expensive
alternative for hte foreseeable future.

144pe...@gmail.com

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Nov 6, 2012, 4:01:45 AM11/6/12
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Five years later, I see your post. If you are still interested in TA-65 I can supply it at a portion of the cost. In fact, I think that I am very close to a significant improvement over the existing product.

Regards
Peter
144pe...@gmail.com

144pe...@gmail.com

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Nov 6, 2012, 4:02:11 AM11/6/12
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