Yohimbine Homebrew

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  1. Its always been like that here Cat.
    For answers to board issues, read the Suggestion and News forum at the bottom of the main page.


  2. Quote Originally Posted by Big Cat
    I can scan the whole studies for you guys in case you want to read them. You need the whole study anyway to see the ratio's they use anyway, although I posted them above. You can also look up Nimni's 1989 patent for free at the US patent website.

    I can also post some references showing where Par Deus ****ed up and why, as demonstrated in the literature, or why skulpt didn't work etc. Since you guys have a nice little homebrew thingy going here.

    I think we should do this more often, have like open source projects for homebrewers to discuss various strategies and improvements on products. Kinda like open source software codes.
    I think I speak for everyone when I say we'd love to read the rest of the study... especially if you'll hook it up without us having to buy it . I know I'd like to read it..... by the way, in the acne study cited w/ use of erythromycin...the prescription acne medication Benzamycin approved in 11/2000 (erythromycin 3%-benzoyl peroxide 5% topical gel) is really close to what Nimni used. It's highly effective...used it myself back in the day and it worked much better than RETIN-A and Differin... Fun facts..
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  3. Oh and while we are on the subject, couple of questions... It has been discovered that the "special delivery solvent" suggested in Par's write up is benzyl alcohol. I am making the assumption that benzyl alcohol is what he is referring to when discussing how lipoderm-Y is able to bypass systemic uptake of the dermal microvasculature. 1. Am I correct with the assumption? If so...2. Why is this the case?

  4. Ok,let me give you a short breakdown, I've read about 25 studies over the past week on percutaneous delivery alone, and my head is about to explode. I mean I spent 2 hours in the basement of the library digging up studies, some that predate 1950. Who would have though there was so much lit ?

    Anyway, Nimni's TPDS is based on the fact that subQ delivery had been demonstrated ( a nice review of this can be found in Maibach and Guy, 1982) and that the nutrients most prone to this were highly amphiphillic (both polar and unpolar), like for instance Thyroid hormones. This was before specific attempts for this type of delivery were made. Nimni based himself on research showing that benzyl can form a micelle together with an organic compound in an aqueous environment. Benzyl is an amphiphillic molecule, and if it can carry these unpolar molecules as a micelle, then they would technically be able to reach the subQ tissue.

    Nimni devised a trans-phase system consisting of two phases. The benzyl carrier, which is amphiphillic and has a high boiling point (less evaporation) and then a more volatile second phase, in Nimni's case a well chosen mix of isopropanol and acetone. Technically any volatile organic solvent would do, but what makes this a beautiful mix is that both isopropanol, and especially acetone, have been shown to enhance the permeability of the skin. Benzyl itself being amphiphillic, is a good penetration enhancer as well.

    When applied to the skin, the second phase evaporates and the compounds are funneled into the benzyl, forming amphiphillic micelles that pass the skin and reach the subQ tissue. The system as is, is simple, cheap, ingenious and quite effective.

    Of course enhancing it is a possibility, but this delivers a number of problems. First of all most penetration enhancers are either amphiphillic of fatty, and all of them good solvents for organic compounds. Since the PE's traverse the skin as well, they may dissolve the compound, meaning it doesn't have a benzyl carrier, resulting in systemic uptake. So the trick is really to find PE's that you can use in very minimal quantities, with maximum effect.

    Another difficulty is application. Ideally you would make it thicker, or work it into a gel, much like the aloe vera idea discussed here. makes sense, since occlusion can enehance skin permeation. But then you basically **** up the TPDS, because the second phase cannot evaporate resulting in the fact that it too traverses the skin to a larger degree, with a large portion of compound dissolved, and as a result, again, systemic delivery.

    These are basically the initial flaws anyone could pick out of the Lipoderm formulas. It contains glycerol and water. There is no evidence that glycerol absorbs, but lets assume it does. The idea is to create excess water in the skin to disturb the polar heads. Except excess water is rapidly taken up into the keratinocytes and has been shown to have no effect in and of itself (Suhone, Bouwstra, Urtti, 1999). So it wouldn't work. Now he adss water to it as well. Glycerol is hygroscopic and attaches to the water creating glycerol 3H2O, which DEFINITELY cannot pass the skin to any large degree. Together with the carbomers and the large volume of PE's, this basically ****s up your system since a lot goes systemic when its either dissolved in the PE's instead of the benzyl, or in the second phase, since that fails to evaporate properly.

    So basically inefficient, pricey PE's in a large volume that **** up the one revolutionary thing about this formula. That and the fact that he left out acetone, while it is a better enhancer of skin permeation than isopropanol is.

    Once you have this all worked out (add benzyl to compounds until completely dissolved, so you have enough benzyl, then add 50/50 mixture of acetone and isopropanol and if you want, any PE that can be used in very low concentrations.

    On to part two. We remember skulpt don't we ? Well, that didn't work. Why not ? DMSO is amphiphillic, it has been found in subQ tissue after apllication. Well basically since its not an effective carrier. the DMSO passes the skin first and then draws the compound through. Resulting in systemic uptake. However the same study that demonstrated this also demonstrated an assymetrical approach works better. Applying DMSO first and then the product, required less DMSO and resulted in greater uptake. So if you want, you can apply DMSO to the skin several minutes before applying your TPDS mixture and get enhanced benefits, much enhanced benefits, especially over time.

    Transdermal delivery has been shown to downregulate with time, but products using DMSO were less prone to this. Probably because resistance occurs in the lipids of the skin and DMSO like compounds are the only ones that affect the protein layer as well, thus experiencing less resistance. So this is definitely a smart idea.

    Just some thoughts to kick around. I'll see if I can scan the studies for you guys this weekend.

  5. Here is the study on indomethacin, the most interesting of the two. I'm sorry for the shabby work, I don't work with a scanner very often and if anybody can tell me how I can adobe professional to get all the scans into one file, that may help me to make the next one a tad easier to make. In the mean time enjoy.
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  6. I didn't see you adressing the points I made. So what are you going to do ? Duck and sling insults and defamations at me, or are you gonna stand up and be the man you claim you are ? Cause I have ****load more studies here that I know you would love to know about ...
    Yeah, that's what I thought ....

  7. Quote Originally Posted by Big Cat
    Yeah, that's what I thought ....
    Sorry, doood, completely forgot about you.

    We just released 5 new products and the sales and enthusiasm has been overwhelming, so it has taken all of my focus and all of my time.

    Pardon me for forgetting about a nobody, who has done nothing, but is trying to make a name for himself to pimp some products to be, by taking on the King.

    Get your free ads somewhere else -- anyone who wants to see how easily you are dealt with by yours truly can read the leptin/LeptiGen "debate".

  8. Quote Originally Posted by Par Deus
    Sorry, doood, completely forgot about you.

    We just released 5 new products and the sales and enthusiasm has been overwhelming, so it has taken all of my focus and all of my time.

    Pardon me for forgetting about a nobody, who has done nothing, but is trying to make a name for himself to pimp some products to be, by taking on the King.

    Get your free ads somewhere else -- anyone who wants to see how easily you are dealt with by yours truly can read the leptin/LeptiGen "debate".
    That's what I thought, wimp.

    yeah, I heard what's been keeping you busy these past days and it sure as hell wasn't the release of your products.

    I really love what you said about the ads too. Shall I start a thread on synthol so you can hijack it and tell all these lovely people about sytenhance ? Or will you be taking out a special 6-page ad report. No thank you, I prefer to let my brain speak for me, rather than pimping crap.

  9. Here is BC making an ass of himself with one of the other leptin experts and brilliant minds in our field, Lyle McDonald (just need to get bitch slapped by Spook, now)

    http://www.cuttingedgemuscle.com/For...&thread****9329





    Quote Originally Posted by Big Cat
    That's what I thought, wimp.

    yeah, I heard what's been keeping you busy these past days and it sure as hell wasn't the release of your products.

    I really love what you said about the ads too. Shall I start a thread on synthol so you can hijack it and tell all these lovely people about sytenhance ? Or will you be taking out a special 6-page ad report. No thank you, I prefer to let my brain speak for me, rather than pimping crap.

  10. Quote Originally Posted by Par Deus
    Here is BC making an ass of himself with one of the other leptin experts and brilliant minds in our field, Lyle McDonald (just need to get bitch slapped by Spook, now)

    http://www.cuttingedgemuscle.com/For...&thread****9329
    Hey, what's the matter ? You too chicken to discuss the matters at hand ? You want to keep running and hiding and posting **** that isn't relevant ?

    You fell off, ****er. You're nobody, you're so pitiful.

    So what's it gonna be ? You gonna show me what you are all about ? Or you want to hide some more.

    Wimp.

  11. Do you understand the concept of "waste of time"??

    That is what you are. You are no one, and I gain nothing from arguing with you.

    I abused you without mercy the other times you tried to show how smart you are.

    Am I really expected to address everything every single little nobody says, until the end of time, until THEY get tired of buzzing around my head?

    Get real.

    Do something significant, make yourself somebody in this industry, bring out 10+ badass, innovative products, run a successful company, get hand picked to do an article in Muscle and Fitness by their PhD from Yale science editor.

    Then, you will be worth my time, and we can have some fun.

    The fly does not tell me if I am going to swat him or not, and him viewing me as a "wimp" is merely good comedy.

    The fly just buzzes around until I decide to squish him.









    Quote Originally Posted by Big Cat
    Hey, what's the matter ? You too chicken to discuss the matters at hand ? You want to keep running and hiding and posting **** that isn't relevant ?

    You fell off, ****er. You're nobody, you're so pitiful.

    So what's it gonna be ? You gonna show me what you are all about ? Or you want to hide some more.

    Wimp.

  12. Quote Originally Posted by Par Deus
    Do you understand the concept of "waste of time"??

    That is what you are. You are no one, and I gain nothing from arguing with you.

    I abused you without mercy the other times you tried to show how smart you are.

    Am I really expected to address everything every single little nobody says, until the end of time, until THEY get tired of buzzing around my head?

    Get real.

    Do something significant, make yourself somebody in this industry, bring out 10+ badass, innovative products, run a successful company, get hand picked to do an article in Muscle and Fitness by their PhD from Yale science editor.

    Then, you will be worth my time, and we can have some fun.

    The fly does not tell me if I am going to swat him or not, and him viewing me as a "wimp" is merely good comedy.

    The fly just buzzes around until I decide to squish him.
    Do you realize how stupid you look now ?

    You are basically saying its a waste of time to adress genuine things that matter, but its not a waste of time to come and comment on my person ?

    Much as I like the attention you are giving me, I'm sure the AM members would be more interested in facts and science instead of your opinions of me.

    Chicken-**** bitch.

  13. Quote Originally Posted by Big Cat
    yeah, sorry about that on my part too, the dude just has a way of getting under my skin sometime.

    no pun intended?

  14. Quote Originally Posted by Big Cat
    yeah, sorry about that on my part too, the dude just has a way of getting under my skin sometime.
    no pun intended

  15. Hehe.

    Fine, I took the bait and went ahead and took you apart on bb.com.

    SQUISH:

    Par Said:


    1) Octopamine interferes with MAO, which breaks down norepinephrine, which is lipolytic, no??
    In addition, some will go deep to the adipose, into the muscle, where beta3 is moe useful in humans. Some will also go systemic, and make it to muscle, where beta 3 is more useful in humans. This is all in the write-up.

    2) Acetone was not included because it does not do much, IMO, for localization. Isopropyl still evaporates far faster than benzyl alcohol. It is gone long before the lag-time at the stratum corneum is over and everything actually starts partitioning. So is the water. It is a good penetration enhancers, but I have several great ones in the formula.

    Acetone would also increase the drying and irritation of the skin, which is bad for user compatability, but could also screw up penetration of hydrophillics, long-term

    3) Which are you referring to?? I surely hope you do not think a significant amount of water diffusses into the body across the skin barrier. If you do, you really need to do some real transdermal research. The rest are for penetration enhancement, not localization of delivery. And, with hydrophillic actives, excellent penetration enhancers are a must.

    4) Please look into the term "lag time" -- water and isopropyl alcohol are long gone before **** things starts penetrating.

    5) Glycerol increases the water content of the skin, which is most helpful with these pesky hydrophillic compounds. It is also useful for preventing dryness, irritation, etc.

    Thanks for playing, though






    quote:
    --------------------------------------------------------------------------------
    Originally posted by Big Cat


    Well these are some that Par has been dodging :

    1) Why does lipoderm ultra contain octopamine when it has been shown that subQ fat barely contains B3 receptors and that the B3 is downregulated when the A2 is blocked (as with yohimbine ?)

    2) Why does it not use Acetone as in Nimni's original design ? It was clearly demonstrated that acetone was a better permeation enhancer than isopropanol, and more volatile, creating an excellent combination for a two phase evaporation before the product is funneled into the benzyl and carried across ?

    3) Why is their such a large volume of relatively inactive, non-volatile permeation enhancers. A lot of these are good solvents for the active ingredients and do traverse the skin, reducing micellar formation with benzyl alcohol and a larger systemic uptake is the result

    4) Next to that volume, carbomers are added as well as glycerol+water. All resulting in occlusion, which may help permeability, but results in less evaporation of the primary phase, resulting in more systemic uptake since isopropanol, with active ingredients dissolved, is now traversing the skin.

    5) Why add glycerol at all , I've seen no evidence that it readily penetrates the skin, and its basically useless if you add water from the get go, since its so hygroscopic you would form a glycerol 3H2O complex that will have even more difficultly traversing the skin, decreases permeation and results, possibly, in more occlusion and less evaporation of the primary phase.

    Answers to these would be greately appreciated by the members at AM as well.



    Well i hope I managed to adress some, if you have more concerns, feel free to post them. [/B]

  16. Quote Originally Posted by Par Deus
    Hehe.
    1) Octopamine interferes with MAO, which breaks down norepinephrine, which is lipolytic, no??
    In addition, some will go deep to the adipose, into the muscle, where beta3 is moe useful in humans. Some will also go systemic, and make it to muscle, where beta 3 is more useful in humans. This is all in the write-up.
    [/b]

    This is all unproven, unsubstantiated and pulled right out of your ass. You know as well as I do it barely penetrates deeper layers in vivo.

    2) Acetone was not included because it does not do much, IMO, for localization. Isopropyl still evaporates far faster than benzyl alcohol. It is gone long before the lag-time at the stratum corneum is over and everything actually starts partitioning. So is the water. It is a good penetration enhancers, but I have several great ones in the formula.
    Of course it is gone swiftly, it evaporates in minutes, which is why Nimni used it. The fact remains that both merely make the skin more permeable, neither has a direct influence on local delivery, but acetone is the better enhancer (onken and moyer, 1963) and is the more volatile solvent, more conducive of the two-phase system. But probably better as Nimni envisioned it to have a dual system for the first phase that evaporates in two steps to ensure you get a funneling effect to the benzyl stage.

    That the isopropyl evaporates wasn't even the issue, your large pool of PE's doesn't evaporate and makes for a good solvent for the products as well, i'd worry about that more. So why bother taking out acetone ? Its cheap, its easy to get, enlighten me.

    Your Penetration enhancers basically suck. Even Patrick Arnold saw that. They are very ineffective and require larger amounts than is suited for the TPD system.

    Acetone would also increase the drying and irritation of the skin, which is bad for user compatability, but could also screw up penetration of hydrophillics, long-term


    Actually irritation of the skin makes it more permeable, you do realise that ? At the SC actions are mostly on the lipid layer, except if you use DMSO or related substances. The best course of action there is to dehydrate it. Water is the least penetrable substance to the stratum corneum. Which is why water influx and efflux was long used as a standard for permeation rates. Of course if you had bothered to read up on skin physiology and some of the older research you would know this.

    3) Which are you referring to?? I surely hope you do not think a significant amount of water diffusses into the body across the skin barrier. If you do, you really need to do some real transdermal research. The rest are for penetration enhancement, not localization of delivery. And, with hydrophillic actives, excellent penetration enhancers are a must.


    I don't, but apparently you do, seemingly so convinced that glycerol will result in hydration of the skin. That is if it could pass the skin to begin with, which it can't if you add water to it, since it is so hygroscopic it would immediately bond to the water leaving you with a large molecule that would never pass the skin. I'm also aware the rest are for penetratuon enhancement, the only thing pertaining to local delivery in your formula is the TPDS. You apparently didn't bother to read up on the fact that benzyl does not cause micellar formation in lipophillic environments, which means that if you have a substantial amount of lipophillic solvents, such as your PE's, then your ingredients remain dissolved, resulting in systemic uptake. You also cause a more substantial bodiful whole that is less conducive to the evaporation of the first phase, resulting small portions of isopropanol not evaporating and passing the skin, so that the ingredients in it are not funneled to the benzyl.

    4) Please look into the term "lag time" -- water and isopropyl alcohol are long gone before **** things starts penetrating.


    The isopropyl is, and one to look up for you is steam evaporation. Anything dissolved in water is, at least for a portion swept with the water upon evaporation. Since this is a stage in which you have micellar formation, that includes not only ingredients but benzyl alcohol as well.

    5) Glycerol increases the water content of the skin, which is most helpful with these pesky hydrophillic compounds. It is also useful for preventing dryness, irritation, etc.


    "Larger amounts of water are either absorbed in the corneocytes or exist as a separate phase in the SC intercellulare regions"

    "Later, however, it was postulated that SC hydration does not lead to an overall decrease in the intercellular lipid disorder"

    Quotes from Mak et al, 1991 and Suhonen et al, 1999.

    That is of course, if glycerol with water bound to it, as exists in Lipoderm, could even pass the skin, which is, as you yourself stated earlier, quite unlikely.

    [Thanks for playing, though
    Here's your ass bro I'm getting tired of handing it to you. But yes, I did enjoy playing. Better luck next time.

    You are so stupid to let me provoke you, you knew I was going to bury you.

  17. Alright Par, your move. You call BC a waste of time and a nobody, but he seems to raise some decent points in his argument. I invite both of you to continue this debate....lets refrain from insults as we have seen too many threads get side tracked a ruined for this reason alone. Keep this going, this is good stuff gentlemen.

  18. yeah, sorry about that on my part too, the dude just has a way of getting under my skin sometime.

  19. Ladies and gentlemen, so far the great Par Deus. But anyway, if there are any more questions, i'd be happy to give you an honest, correct and direct answer.

  20. I addressed his points.

    He knows **** all about this.

    Just like he knows **** all about leptin.

    Just like he knows **** all about VAT and cortisol disfunction.

    Like I said, do something worthwhile, make yourself somebody in our world, and it will be worth my time.

    If some of you believe him, fine. There is not a thing I can say or do to convince such people, at this point, because such people are wholly ignorant of this subject.

    Call me a ***** and declare yourself victorious.

    I don't ****in' care.

    It is 100% laughable to anyone who has a clue on these subjects.

    I consider you a joke.

    Lyle McDonald considers you a joke.

    Pat Arnold considers you a joke.

    Spook considers you a joke.

    Not one person of science in this industry considers you anything but a joke (if they have even heard of you)

    Guess why....?

    'Cause you are a joke.

    An incredibly insecure, ego-starved, borderline psychotic joke.

    The great Par Deus has proven himself over and over again.

    You haven't done a ****ing thing, except run your mouth.

    I am sorry that you do not like how I treat you, but I got no love for hoes.

    Never have.

    Never will.

    But, by all means, answer their questions

  21. Bitch Fight!!!!! Wahoooooooo

  22. so where can i get acetone?;-)

  23. Quote Originally Posted by wojo
    so where can i get acetone?;-)
    Local drug store.

  24. nice i love absolved and was researching syntehance..thank god i suscribed to this thread a long time ago i forgot it existed..looks like im gonna try a acetone iso and ba homebrew(ghetto version of syntehance) of 4-ad 1t..tooo broke for syntehance.

    thanx cat
    ur the man.

  25. Quote Originally Posted by Par Deus
    I addressed his points.

    He knows **** all about this.

    Just like he knows **** all about leptin.

    Just like he knows **** all about VAT and cortisol disfunction.

    Like I said, do something worthwhile, make yourself somebody in our world, and it will be worth my time.

    If some of you believe him, fine. There is not a thing I can say or do to convince such people, at this point, because such people are wholly ignorant of this subject.

    Call me a ***** and declare yourself victorious.

    I don't ****in' care.

    It is 100% laughable to anyone who has a clue on these subjects.

    I consider you a joke.

    Lyle McDonald considers you a joke.

    Pat Arnold considers you a joke.

    Spook considers you a joke.

    Not one person of science in this industry considers you anything but a joke (if they have even heard of you)

    Guess why....?

    'Cause you are a joke.

    An incredibly insecure, ego-starved, borderline psychotic joke.

    The great Par Deus has proven himself over and over again.

    You haven't done a ****ing thing, except run your mouth.

    I am sorry that you do not like how I treat you, but I got no love for hoes.

    Never have.

    Never will.

    But, by all means, answer their questions
    And this, my friends, is everything Par Deus stands for. He calls himself a person of science. He doesn't have a scientific bone in his body. He doesn't even have a degree remotely related to science, established himself in the least bit as a scientist or anything related. The only thing he does well, is read abstracts and compile a list a of references he's hardly even read (just look at his comprehension of isopropyl and acetone in the TPDS) whenever he thinks he has something new and exciting, not even caring if it will actually work, let alone be worth the money

    He is currently drowning, attacking anyone for an opinion that differs from his, because it may lose him one customer. Trolling message boards like bodybuilding.com like a common post-whore, in the hopes of slightly retaining some sort of clientele. Avantlabs, is drowning. And Caleb's pitiful reaction, and panicky accusation's prove it.

    You see, what he says is correct, all these people don't think much of me at all. I'm not going to hide the fact that I made mistakes in the past. I made a lot, and the further you go back, the more laughable they probably are. But now we are several years, many studies and one and a half (science) degrees later. Caleb is still the same pseudo-scientist he was then, while me, that same chump he refers to earlier, is now running circles around him. And he doesn't even realize that in ridiculing me, he ridicules himself, because I've already demonstrated i'm better now, and still growing.

    This lowly individual is so deluded he even thinks I would pimp something on this board. This board, which is known for its homebrewing, for people with knowledge, sharing information and helping each other find cheaper and more effective alternatives to the crap people like him put out. Give me a break.

    Unlike your own board Par, people here actually think and help each other, instead of kissing up to the great leader. The science has been posted, it has been discussed. I hadn't cried victory, Icried for more discussion, because that in the end, is what helps the sport. Remember ? That's what it used to be about. The science and helping people. But I doubt you remember. But I will cry victory now, this response shows you fell off. It tells me I'm finally at a level above you, and with so much room left to grow its amazing.

    So people, I presented you with the facts. Par can't even adress the facts, he would much rather insult me and bring up my past mistakes. Past mistakes that I made in a process of learning and helping others. Mistakes that made me the man that just handed him his ass. I'm not ashamed of where I came from, anymore than you are pitiful.

    So close this little chapter, and lets get back to discussing this topic. Do we have any other questions or issues that need to be adressed ?
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