- 09-22-2003, 04:24 PM
The Benzyl A. should disolve the Yohim. fine. I found that all I need to do is disolve the yohim and whatever other ingrediants in the Iso Prop. and then add it to the aloge gell. This would work even better with the BA. I think we should try a homebrew of Lipoderm Ultra.
This is what im thinking:
Same Yoihim homebrew formula but instead of DMSO add 2% BA. Also drop some of the ISO and add 3-4% more BA. BA is the main ingrediant which causes the localized delivery. This is what we want, we want as little system uptake as possible.
Now .... for every 4oz of homebrew add
3.5 grams Yohim. HCL
1gram Of Green Tea Extract
1 Gram caffein Anhy.
1 Gram Aclar
You may want to bump up the caffeine to 2 grams. There should be not systematic sides form the caffeine as it will work as a localized diruetic for the water retention from the Yohim HCL.
Im going to try and tweak the actual gel formula little....I want to design a carrier that will deliever mostly hydrophilic substances but also will deliver a substantial amount of lipohilic ones also. Par says the carrier for Lipo Ultra will eb abel to deliver andrgoens, and other lipophylics along witht he Yohim and caffeine.
- 10-05-2003, 01:33 AM
I got this from Kitchen Chemist @ Alchemy
"Do not use that recipe for those, you want it to be for localized fat and the above recipe is designed to get into your blood stream. Here's the recipe i use for yohimbine, i'm not sure how well the other stuff will dissolve in it though.
Original instructions were
55% Aloe Gel (100%)
8% menthol solution
Y-hcl 3.5g 1 month supply
I couldn't get that to work as i was using 6g of yohim per 240ml, the solution kept screwing up and the yoh wouldn't stay mixed, so here's what i did :
Take two identical bottles that you know what the spray volume is or pump volume is.
With a accurate syringe, fill one with water till its 240ml. Mark the line on the bottle at that point. Now in these steps, Put :
6g Y-hcl in unmarked bottle
Add 20ml of iso/menthol combo
Add 5ml of dmso
Add 24ml of pg
Add 40ml IPM
Put the above ingredients in hot water for 15-30 minutes to let yohimbine dissolve.
Fill bottle to 240ml line with aloe gel.
Shake like crazy and you're done.There is no water in this as i found that to cause all the clumping probs.
For the iso/menthol combo, i took 100ml of iso and dumped 66g of menthol in it and heated till crystals were dissolved."
It looks good. I didn't know menthol type things pushed things to fat cells...
what you guys think?
10-09-2003, 03:31 AM
60% aloe to make it a gel
10% propylene glycol(a must for hydrphilic substances)
10% d-limonene( shown to be a good penetrant for hydroliphics)
8% water (It will promote absorption of hydroliphics)
Is this the final agreed Formula??
10-09-2003, 01:37 PM
thats not what I would reccomend. I would go with a higher BA % as this is the real localizing agent. If it isnt localized, there is no point to making a topical. Maybe drop some of the aloe gel and add a little more water and BA. Jsut my opinion..
11-25-2003, 10:12 PM
My topical Yohimbe Formula
How's this look fellas?
55% Aloe Gel
10% Prop Glycol
My question is, how should it be mixed? I was also wondering if d-limonene would work as well as menthol crystals. If so, how would I dissolve the crystals to make it at the correct potency? I wil also add 2 grams of caffeine as well as 7 grams of Yohimbe HCL to make a 240ml bottle. What are your thoughts on this?
11-26-2003, 12:16 AM
I HIGHLY HIGHLY doubt that the Yohimbine will come close to dissolving in that combo of ingredients bro.
11-26-2003, 04:53 AM
Why don't you think that yohimbe will dissolve in this combination of ingredients? All of the other formulas in this forum are similar to this one. What do you think I could do to make things work better?
01-11-2004, 12:54 AM
it has been a couple of weeks and I'm curious as to what is best? yohimbe localized should be the goal. what's the easiest formula for hormones without an ester? anybody?
03-04-2004, 04:58 PM
wow, if I knew it was such a big mystery I would have posted this sooner. If you want to make something better than Lipoderm, you could start by using the trans phase delivery system Par Deus tries his best to conceal, but then use it correctly. Marcel Nimni designed the TPDS in 1989 and patented it. It consists of 10% benzyl alcohol, 40% acetone and 50% isopropanol. But the idea is to create a two-phase system, one with a high boiling point that is very stable to carry the product (BA) and one that evaporates easily (acetone and isopropanol). BA is well suited since it dissolves most organic materials, and is moderately hydrophyllic, so it dissipates slowly through the epidermis and dermis and even the underlying tissues.
So Basically what you do is determine how much product you need, then add BA until it completely dissolves, then you fill up to the volume you want with a mixture of 4 parts acetone and 5 parts isoprop, or any mixture of organic solvents that evaporates easily.
The need of further penetration enhancement at that point is not required, the BA itself is tipped as a much better PE than for instance propylene glycol. If you do decide to add other PE's, add only ones that work on the stratum corneum, anything that works beyond that will speed up delivery and make you get more systemic uptake. DO NOT add Glycerol and water. Contrary to what you may have been told that principally leaves BA/yohi mixture on the skin, and you get a larger loss of product. That's not me talking, but marcel Nimni.
For those who want more information, there are 3 or 4 studies on TPDS and anyone can get the patent application off the net completely free (pat nr 4820724). Or just ask.
Basically, localized delivery is in its early steps, there is so much room for improvement, Lipoderm will look like placebo in a short while.
03-08-2004, 10:42 PM
03-09-2004, 02:55 AM
03-09-2004, 01:30 PM
I forgot this thread existed. I thought this died a long time ago. Par is the information wrong or just outdated?
For answers to board issues, read the Suggestion and News forum at the bottom of the main page.
03-09-2004, 03:43 PM
Originally Posted by Bobo
He is correct that benzyl alcohol is the special carrier, and not totally out there on the homebrew instructionjs, but I have not exactly gone out of my way to hide it -- it is referenced in the ****ing write-up.
The rest he seems to have pulled from his arse, as he is known to do.
03-09-2004, 05:49 PM
yeah, I'm clueless, and that's why you don't want to dignify that. Get a ****ing life. I can name several problems with Lipoderm.
First of all you left out acetone. Not only is acetone better at increasing the permeability of the skin, it also evaporates easier than isopropanol making passing of the active product to the benzyl carrier more likely and more accurate, but heck, nimni didn't know what he was doing right ? Why did you leave it out ? I hope it wasn't because of patent considerations, because the 1989 patent clearly states one or more volatile solvents, so if he found out he'd be all over you anyway.
Second problem is that you seem to keep forgetting that this evaporation is crucial for the trans-phase to occur. You employ a lot of penetration enhancers that require significant quantities. However if you had bothered to do some column chromatography on your product you'd know that benzyl only solidly maintains its micellar protection on ingredients in aqueous surroundings. Its much less likely to do so in lipophillic surrounding. With your current product a lot of the product would make it through without transferring to the benzyl phase, resulting in greater systemic loss of products. Something that was painfully obvious with ab-solved apparently, since the more lipophillic ingredient readily dispersed across the larger volume of PE's.
Thirdly you added glycerol and water. glycerol would bind to the water and the resulting glycerol 3H2O compound would not easily traverse the skin. What it would do is prevent evaporation, prevent action of many of your lipophillic PE's etc. The point I assume is to increase water content in the skin, but excess water is drawn into the keratinocytes and the increase in permeability resulting from the disruption of the polar heads was found to be minor, even in the 4-5 time increase of hydration after occlusion.
Occlusion is very good to discuss of course too, as the glycerol 3H2O and carbomers would no doubt cause some occlusion preventing evaporation of the primary phase of TPDS, again resulting in less localized uptake.
Sounds to me like you didn't really do your homework on this one. Something you later proved by adding octopamine to a product containing yohimbine that targets local subq tissue ....
03-09-2004, 07:20 PM
I first need to note the utter humor of a guy playing expert, when less than two years ago, he did not even think passage of actives across the skin was possible -- a guy who proclaimed the superiority of oral 4-AD -- and a guy was not afraid to state such idiocy as fact in his prohormone article on bb.com
Remember that, sunshine?
Or how about before that when you went on and on telling people how 1-AD would not work and got smacked about by Pat Arnold.
Or your theory on how ONE+ localized delivery because it made your traps and shoulders grow faster than other parts.
You have a long-existing tendency to state nonsense and ignorance as fact, that is for sure.
You are in so very, very far over you head on this (just as you were with leptin/LeptiGen and VAT/cortisol/Ab-Solved), despite your ability to quote and randomly intersperse jargon.
Lipo Ultra is a whole different animal from original LipoDerm, as far as the carrier complex. But, you do not understand how avoidance of systemic uptake is avoided in general -- hints: 1) it ain't by slowing down diffussion and 2) Nimni gives his theory in one of the papers -- so, it is moot to distinguish it from your attempt based on that misunderstanding in regard to LipoDerm-Y.
If, and when, you make a product with all of your "knowledge" (which you seem to be trying to pave the way for), it will get ****ing buried by Lipo Ultra, just like Tren-X got buried by ONE+ and just like anything else you could try to do that involves matching minds with me.
Stick to being an above average intelligence bodybuilder -- it suits you far better.
03-09-2004, 07:35 PM
Yes I most certainly do. Its mistakes like that which taught me the relevance of doing full and complete research, precious. Which is why now, two years later, you are resorting to digging up dirt instead of hitting the library.Originally Posted by Par Deus
Nothing random about quoting the facts and proving you wrong.You are in so very, very far over you head on this (just as you were with leptin/LeptiGen and VAT/cortisol/Ab-Solved), despite your ability to quote and randomly intersperse jargon.
Its not by slowing down diffusion, I figured that one out on my own by now, and admittedly was wrong in stating such. Before you go around "assuming" what nimni said you need to reread those studies, as well as the references in those studies. Including the patent.Lipo Ultra is a whole different animal from original LipoDerm, as far as the carrier complex. But, you do not understand how avoidance of systemic uptake is avoided in general -- hints: 1) it ain't by slowing down diffussion and 2) Nimni gives his theory in one of the papers -- so, it is moot to distinguish it from your attempt based on that misunderstanding in regard to LipoDerm-Y.
I just pointed out several inferiorities in your product, which is only one thing. I not only did the research to work out the kinks, I also managed to dig up some research that basically makes lipoderm look like a placebo. But that's future talk isn't it ?If, and when, you make a product with all of your "knowledge" (which you seem to be trying to pave the way for), it will get ****ing buried by Lipo Ultra, just like Tren-X got buried by ONE+ and just like anything else you could try to do that involves matching minds with me.
I'm not a bodybuilder, don't have the heart for it and wouldn't want to insult those that do by calling myself one. I am a trainer of bodybuilders, and a damn good one, as I intend to prove at the IFBB world championships. I'm also a molecular biologist that is currently adding a lot of practical experience with his biomedical and biopharmaceutical technology studies. Which, I believe, is more education than you ever enjoyed in this department. But please, correct me if i'm wrong.Stick to being an above average intelligence bodybuilder -- it suits you far better.
Which leaves me with but one thing to say :
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 ...
03-10-2004, 10:35 PM
In case you all are interested...
Delivery of erythromycin to subcutaneous tissues in rats by means of a trans-phase delivery system.
Peng L, Nimni ME.
University of Southern California School of Medicine, Department of Surgery, Los Angeles 90033, USA.
Topical administration of antibiotics is associated with reduced risk of systemic side-effects and alteration of gut microflora, and results in higher concentrations of antibiotics at the site of application (and so a lower dose of the drug is required). In conditions such as acne vulgaris, infiltration of the antibiotics into the infected subcutaneous layers is highly desirable. A trans-phase delivery system (TPDS), a mixture of benzyl alcohol, acetone and isopropanol, has been shown to enhance the effective transport of the antibiotic erythromycin across the epidermal barrier and enhance accumulation in the dermis. Two formulations containing N-methyl[14C]erythromycin were compared, a TPDS solution and a propylene glycol solution. They were applied to the dorsal areas of 4-6 week old Fischer rats and tissues were removed for analysis of radioactivity after 2, 4, 8, 12 or 24 h and skin was biopsied and sectioned for autoradiography. The erythromycin dissolved in the TPDS solvent mixture penetrated the stratum corneum and a relatively high concentration was maintained in adjacent tissues for up to 24 h. Penetration was very effective and the erythromycin was detected in significant amounts in the underlying muscle, various organs and later in the urine. In contrast the propylene glycol carrier, probably because of its primarily hydrophilic character, caused the erythromycin to traverse tissue barriers rapidly and appear in the urine. Microautoradiographs qualitatively revealed progressive disappearance of radioactivity from the surface; this correlated with results obtained by direct isotope counting. The route of penetration, in addition to following the interkeratinocyte spaces, seemed to include the perimeter of the pilosebaceous glands and their appendages before diffusion into the capillaries. The propylene glycol solution seemed to traverse the epidermis and the papillary and reticular dermis more rapidly, which might explain its rapid appearance in the urine. These data suggest that the different solutions penetrate the skin by different mechanisms.
03-10-2004, 10:37 PM
Transdermal delivery and accumulation of indomethacin in subcutaneous tissues in rats.
Mikulak SA, Vangsness CT, Nimni ME.
Department of Biochemistry & Molecular Biology, School of Medicine, University of Southern California, Los Angeles 90033, USA.
Oral non-steroidal anti-inflammatory drugs (NSAIDs) are effective pharmacotherapy for a wide variety of painful, inflammatory disorders. Development of an efficient means of topical administration of NSAIDs could increase local soft-tissue and joint concentrations while reducing systemic distribution of the drug, thereby reducing side-effects. With this in mind we studied the effects of a novel topical penetration enhancer for lipophilic compounds, a trans-phase delivery system (TPDS), a solution of benzyl alcohol, isopropanol and acetone, on the distribution of indomethacin in various tissues locally and remote from the site of application. We compared the TPDS with a 50:50 (v/v) mixture of propylene glycol and ethanol, a commonly used penetration enhancer, and with oral administration. We found that the TPDS was significantly superior to the other approaches at achieving high local-tissue concentrations in the vicinity of the site of application. In addition, comparison of these two carrier systems seems to clarify the different aqueous and hydrophobic pathways of drug penetration which emerge from various experimental findings and theoretical considerations. Our results suggest that this non-aqueous solvent system, and benzyl alcohol in particular, because of its unique physicochemical and solvating characteristics, might be able to deliver therapeutic levels of indomethacin to tissues close to the site of application in a safer and more effective manner than presently accepted forms of delivery.
03-11-2004, 10:14 AM
03-11-2004, 02:37 PM
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.
03-11-2004, 08:03 PM
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.
03-11-2004, 08:58 PM
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..Originally Posted by Big Cat
03-11-2004, 10:03 PM
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?
03-12-2004, 02:44 PM
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.
03-13-2004, 02:36 PM
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.
03-22-2004, 09:42 AM
Yeah, that's what I thought ....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 ...
03-22-2004, 11:18 AM
Sorry, doood, completely forgot about you.Originally Posted by Big Cat
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".
03-22-2004, 12:18 PM
That's what I thought, wimp.Originally Posted by Par Deus
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.
03-22-2004, 01:12 PM
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)
Originally Posted by Big Cat
03-22-2004, 01:58 PM
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 ?Originally Posted by Par Deus
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.
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