#31

better to take it with 200 to 400 mg ketoconazole available(unless they are out of stock) from india like Reliable… where i bought mine.

#32

even though rapamycin has greater solubility in benzyl alcohol i have read that it is not as readily released from that as it is using some other agents in which it has a lower solubility than benzyl

#33

FWIW use DMSO dissolved and carry the rapamycin.

#34

yes i have been making an injectable solution or whatever u want to call it from powder from China.Trying to make nano micellar solutions. Have read that Nanoemulsions are even better though difficult and need be much more precise than just micellar solutions. Seems to me that just taking it orally esp if using just the straight powder is a real waste and doubt that sublingual is going to be any help either.

#35

just how would u go about looking for signs of cytotoxity or whatever without a lot of expense and going thru a royal pain in the ass ! ALso to the remark
" I wouldn’t recommend injections whatsoever. " Studies done with mice say just putting it with their food had no effect at all while intraperiontal injections which are not really suitable for humans i would not think because for one - horrible unbearable pain, had much effect. But for sure subcutaneous, im or iv if u can do it yourself - like i mean hit a vein which i can’t, injections would all be way better than oral and save u money as rapamycin even as wholesale powder is NOT cheap.

’

1 Like
#36

So, to address your first response regarding benzyl alcohol - yes, it has slower release time. This is because “like dissolves like” applies here.

The more similar a compound’s kinetics and properties are to its solvent (i.e. lipophilicity, surface charge/area, viscosity), the more readily it will dissolve in said solvent and reject others. This is the basis for most long-acting injections like testosterone, which is usually esterified into compounds like testosterone cypionate, which is many times more lipophilic than plain testosterone and thus will separate more slowly from its preferred solvent, oil.

Now, whether or not you want sustained, gradual release of rapamycin like this is debatable. I have no idea about the pharmacokinetics of such an injectable preparation of rapamycin, but if it ends up being similar to a long-acting injectable, you’d essentially be replicating a daily dosing regimen that cancer/transplant patients use, which has its own issues.

To address your second reply regarding nanoemulsions, I think you may be misunderstanding the purpose of such preparations. They are not typically intended for injection.

Injectable preparations are considered 100% bioavailable. This is because you use a parenteral route, bypassing saliva, bile acids, and liver metabolism. In other words, you avoid anything that could potentially degrade or inactivate your active drug.

Nanoemulsions are intended to make up for the limited bioavailability of oral preparations. Most drugs have poor solubility in aqueous solvents, especially so for rapamycin, so the idea is to encapsulate them in a carrier lipid which is also miscible with water; this allows the drug to be more readily absorbed by the intestines.

Creating nanoemulsions, or even micellar ones, requires very precise and controlled laboratory conditions. It isn’t something that can be achieved at home, unless you bootleg some specialized lab equiment (which you usually need a license for, even secondhand).

So, for IM and SC, nanoemulsions wouldn’t make much sense since you’re not injecting into aqueous environments. For IV, it would matter since blood is aqueous, so you may see nanoemulsions used here in order to bridge the aqueous solubility issue. Most people here seem to be aiming for IM or SC, which is far easier to prepare and use than IV. Furthermore, IV preparations need to be used fresh every time since aqueous solvents have very short shelf lives, so it would be extremely difficult to do at home.

And yes, taking the raw powder orally, even when packed into a capsule, is basically like ingesting nothing. Most of it will be destroyed in bile acids, and most capsules marketed as “enteric-coated” are actually fake, since you’d need a pharmaceutical license to make enteric capsules due to regulations in the US. However, I do have methods for preparing enteric-coated tablets at home which can bypass the stomach acids, so let me know if you’d like a how-to for that. I can’t guarantee that it’d have the same performance as the factory-prepared ones, but you can get pretty damn close.

Just keep in mind… making your own medicine is illegal. So, if you purchase any medicine-making equipment, it will put you on a list. The FDA and DEA do not fuck around with homemade drugs. If they suspect you are making drugs of any kind, be wary of getting raided. Usually most people will fly under their radar, but if you have an online record of buying pharmaceutical equipment (ESPECIALLY tablet/pill presses) without a license… yeah… they might start monitoring you. Buying the ingredients is fine, but buying equipment implicates you as a manufacturer and/or distributor.

When your tissues start to necrose, deteriorate, or other similar effect. Cytotoxic just means that cells begin to malfunction and die. I’m assuming you’re talking with regard to DMSO, which is generally safe when kept to a concentration of 10% or lower. However, even at 100%, you should be fine as long as you rotate sites and keep injection volume low. It just tends to sting like a bitch, but tolerance can vary between individuals such as with MAC, who has no reaction to it. Cytotoxicity really only appears if the same site is exposed repeatedly over a long period of time. To date, only a few cases of this have been reported from people drinking bottles of the stuff for some reason.

This is just a disclaimer that I usually have to put because of my background. The pharmacokinetics of injectable rapamycin in humans, aside from a few IV trials, has not been well-investigated. We have no idea how IM or SC administration would perform. Therefore, I cannot recommend it.

The reason I still give advice is because of harm-reduction. That is, if people are going to self-experiment anyways, they should at least know how to do it properly in order to reduce the overall risk.

I suppose the economics of it would be better, but keep in mind what I mentioned earlier regarding pharmacokinetics. Saving money per dose is a rather tiny detail compared to the overall unknown of such a radical treatment. I’d be more concerned about the impact on your overall health rather than price per bioavailable dose, since the former can end up costing you far more than you’d save on a kilo of powder.

2 Likes
Are low weekly doses like 1mg or 2mg, helping with longevity?
#37

most all tests with animals are injections and much about the success of that way but very little or none the other way being oral. people are animals/whats good for the goose is good for the gander to put it in old simplified wise tales language.

#38

Dan - almost all the rapamycin mouse studies have been using oral dosing of rapamycin. We have a full list of the studies here if you want to learn about them: List of all the Mouse Studies Showing Rapamycin Lifespan Extension

You really don’t seem to understand much about rapamycin and the risks that you are taking, and don’t seem to have much interest in learning about them. You are taking extremely high risks and the outcome is not likely to be good, or a longer life. I think what you are doing is really reckless. The contributor who posted above is a biochemist who works in this field and works daily with these types of drug issues he discusses above. If you don’t want to listen to educated, thoughtful feedback from people on rapamycin use, this may not be the forum for you. We don’t want to see anyone hurt or die from reckless rapamycin use.

2 Likes
#39

i have been doing it for a year or so and from the many articles on internet i use propylene glycol, polysorbate 80=tween 80 and alcohol of which i use isopropyl as it is cheaper but u can use either that or ethyl if u want to pay more. I NEVER ever had any plans to do it orally since it is much more effective and superior and sensible to do it by injection as most all animal and mice/rat tests are done by injection and compared to oral its a no brainer. I also bought mine from a chinese supplier of which i trust from buying other chemicals etc. for over 8 years; i have had results and side effects and blood tests results just as to be expected from internet reports so i feel confident my rapa is sufficiently good . if u insist on doing it the inferior oral way i have briefly read similar scientific reports on internet which have shown directly how to formulate it to be significantly superior to the commercial rapammune or however u spell it oral product… i also do mine with 200mg ketoconazole every 5 days averaging about 20 to 30mg rapa with some breaks and delays because of the horrible mainly mouth sores problem enough so as to even make it quite difficult to eat. Finally i said well i am going to wait till all these mouth sores are gone before doing any more which took over 2 months. i can just imagine what these mice and rats are going thru since scaling to them they were doing much more than my measly 20 to 30 mg. and not only that every day! Now even so i am planning to cut back and have to say only 7 to 10mg every 5 days with ketoconazole. Even that measly tiny amount has been enough to still get mouth sores though at least for me.

,

#40

i have read articles on mouse studies and most all of them were intra-periontal injections which are usually not done to humans. The foremost article i read when they just put it with their food by what’s the word ‘gavage’ or something and the results were not effective. so i guess it just depends upon what articles u choose to read. My thinking is always rational and logical and scientific and relative probabilities. The chinese company i use i have dealt with them for over 8 years buying other chemicals so i am confident enough with them. Sure some people have had bad luck from chinese vendors but china is a huge huge country so ofcourse there are going to be some undesirable but i will bet if u take those who have had success is much much greater. To you and others i guess u just don’t trust any foreign country. Do u go thru all that testing etc etc from products from usa vendors - i doubt it. Anyway using sensible probabilities i would say i am taking less chance of undesirable issues than someone who risks death and serious injury from driving an automobile over 10,000 miles a year. As far as scientific and doctors etc who u seem to think know much more why don’t ask one of them the answer to the simple question of 2nd derivative of exp(sqrt(x)) wrt x. And see how many of these ‘bright’ doctors can’t answer that right off the bat or in small amount of time. Yea they are really bright.! Anyway i am not saying anyone else has to do the rapamycin the way i do it. I am just giving my take on the issue. And i even said if u insist on doing orally then go ahead. And i am only doing it for myself only and NOT selling or propose to ever sell it to anyone else.

9x(

#41

If your rapamycin powder is accurately measured, 7 to 10mg with ketoconazole it could be equivalent to up to 40mg to 56mg every 5 days, so an average of almost 10mg/day. This is much higher than the transplant organ patients use (and more at the levels used in cancer studies) and so you are likely getting very significant immune system suppression on an ongoing basis. This is very high risk.

Below are some examples in a high dose (e.g. 10mg/day) everolimus study for cancer patients where there were multiple life-threatening situations, including a relatively sudden death of a 27 year old woman due to e-coli sepsis.

Rapamycin is not a risk-free drug, especially as you increase doses above the regular 5 to 8mg dosing once per week level.

The most common Adverse Effects (AEs) of everolimus therapy were laboratory abnormalities (100% of patients) and infection complications (83 episodes in 15 patients). Infectious episodes of pharyngitis (67%), diarrhea (44%), stomatitis (39%), and bronchitis (39%) were the most common infections. They were mostly mild or moderate in severity (grade 1–2).

In two cases, life-threatening conditions related to mTOR inhibitor treatment were encountered. The first was classified as grade 4 pleuropneumonia and Streptococcus pneumoniae sepsis, whereas the second was classified as death related to AE (grade 5) Escherichia coli sepsis.

A 27-year-old woman with TSC was started on everolimus
treatment because of AML of the left kidney
(60 Å~ 48 Å~ 36mm in size). The other signs of TSC were
facial angiofibroma, hypomelanotic macules of the skin,
and shagreen patch. The diagnosis of TSC was made
12 years earlier when the patient underwent nephrectomy
because of a large tumor of the right kidney. The
patient received everolimus at a dose 10 mg/day and the
trough concentrations of the drug ranged from 4.08 to
5.08 ng/ml. After 3 months of everolimus therapy, a
reduction in AML was observed (40 Å~ 31 Å~ 20mm in
size). During treatment, hypercholesterolemia (309 mg/
dl) and transient leukopenia (3.2 Å~ 109/l) with neutropenia
(1.34 Å~ 109/l) was observed. She also reported
oligomenorrhea. After a gynecological consultation, a
functional ovarian cyst was identified and contraceptives
were prescribed. However, 2 weeks later, she was
admitted to the gynecological unit because of subabdominal
pain and an ovarian cyst (64 Å~ 53mm in seize)
on ultrasound examination. Torsion of the ovarian cyst
was suspected. On the day of admission, WBC was
9.2 Å~ 109/l, the absolute neutrophil count (ANC) was
6.6 Å~ 109/l, the hemoglobin level was 10.8 mg/dl, the
PLT count was − 275 Å~ 109/l, and the C-reactive protein
concentration was 8.0 mg/dl (normal < 5.0 mg/dl). The
patient was advised to continue intake of contraceptives
and everolimus. The next day, the general condition of
the patient aggravated. Her blood pressure was low (85-
/50mmHg). Her WBC and ANC decreased (WBC
−2.4 Å~ 109/l, ANC − 1.8 Å~ 109/l), whereas the hemoglobin
level (11.0 g/dl), the PLT count (185 Å~ 109/l), and coagulation
tests were normal. Computed tomography of the
abdomen and pelvis showed AML of the left kidney (size
as in the previous examination), an ovarian cyst measuring
65 Å~ 50 Å~ 40 mm, and fluid in the retroperitoneal
space with density of the blood. Further aggravation of
her general condition was observed. The patient was
transferred to the ICU and she died after 2 h with
symptoms of shock and multiorgan failure. Blood and
urine cultures collected when she was in the ICU were
positive for Escherichia coli.

Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening

https://sci-hub.se/10.1097/CAD.0000000000000207

#42

What the hell… you’re injecting with “cheap” isopropanol?
Dear God, when you say “cheap” I hope you don’t mean you’re injecting yourself with the grocery store rubbing alcohol. That is NOT intended for injection! I hope you are aware of the different standards for chemical production. The grocery store isopropanol has tons of contaminants that, when used superficially on skin, don’t cause any issues. However, once ingested or injected, these contaminants can bioaccumulate in your tissues. Not good stuff.

Please attempt to source pharmaceutical ethanol. Your other ingredients are fine provided that they are sterilized and are of pharmaceutical/USP grade, but isopropanol is just horrible to use as an injection. For one, it’s toxic; this is not going to be great for your health even at low doses.

I can think of exactly zero pharmaceutical companies that make anything injectable for humans that contains isopropanol.

You’re flying completely blind. There have been absolutely no studies in humans of the pharmacokinetics of injectable rapamycin. Furthermore, your excipients can drastically alter the pharmacokinetics in ways you cannot possibly predict without a laboratory environment.

Furthermore, as RapAdmin says, most of the mice studies are not injected - they are fed it in chow. Even among mice, injections are sparse since it is quite labor intensive to inject hundreds of mice each and every day of the study.

It is by no means a “no-brainer,” because you have completely nil data on how it will work in your body.

Furthermore, how are you ensuring your injections are sterile? I see no mention of your procedures at all. I hope you aren’t doing it in a non-sterile manner, as that risks horrific infections. Given that you state you get your advice from the “internet,” I have a bad feeling about your answer…

I seriously doubt the credibility of both your vendor and your supposed test results.
Side effects and blood test results can only go so far in determining your overall health. The question is what blood tests, and what side effects. Most people, for instance, feel perfectly fine inhaling carbon monoxide, until they pass out immediately after. How you “feel” and what you “believe” are never good measures of how you actually are.

Oral routes are not inferior. They are simply different routes of administration. Injections simply increase bioavailability and/or release profiles. In my opinion, there really isn’t a reason to opt for injections when you can achieve a therapeutic dose via the oral route just as effectively. This, of course, depends on what your end goal is, but I suspect your goal isn’t based on any scientific rationale, but rather dollars per dose. That is not a healthy nor safe way to look at this.

Never briefly read. Thoroughly read. Skimming details leads to disastrous consequences, especially for homebrewed medicine.

Dear Lord! You’re taking 20 to 30 milligrams!? And not only that, but injecting it? No wonder you have mouth sores so severe you cannot eat! That is a serious side effect, not a minor one!

The reason mouth sores appear is partly due to immune suppression, where viruses in your mouth become opportunistic. It’s an indicator that your immune system may be severely compromised. This is not ideal at all.

Furthermore, your dose is many times higher than even the most dire cases of organ transplant patients! How did you arrive at a 20-30 mg dose? What kind of papers are you reading!?

Repeat that last part, but slowly.

The fact that you did not take the time to even Google the definition of gavage before posting concerns me, as that says to me you aren’t really reading or understanding these scientific papers well.

That is not how it works at all. You don’t choose what to read. You. Just. Read.
You can’t cherry pick articles that support what you want to believe. That’s not science, that’s confirmation bias.

I don’t even know how to respond to this.
I’m not even sure you fully understand how ridiculous “relative probabilities” sounds.

Don’t trust, verify. Self-medication is not a “just trust me bro” thing. Not at all.

Not just some people. A damn lot of people.
You’re forgetting that different countries have different laws. And Chinese laws are certainly not up to the standards of pharmaceutical standards elsewhere in the world.

US vendors must pass through far more strict and controlled regulations and quality standards than that of other countries. Even with India, the products that are exported to Europe or the US have to be held to a much higher standard than what is sold within India or other non-western markets. It just isn’t comparable.

How the F did you come up with that math? Sensible probabilities? Brother, you don’t even know what you’re doing to your own body.

That doesn’t even make any damn sense! Knowing basic calculus doesn’t mean you automatically know how to prepare sterile pharmaceutical preparations, let alone know how such an experimental regimen will affect your body.

In addition, nearly every pharmaceutical expert knows how to do that basic derivation. That’s high school calculus, I mean come on! Knowing it off the bat is not impressive.

What is impressive is whether or not you can do this on the fly:

image

Now you don’t need to solve this. None of us do this by hand, we use calculators. However, do you recognize this formula? I’ll give you some credit if you at least know what it is.

In any case, I think you should look up a guy named David D. and his friend Justin K. But I doubt you can figure out what I mean by that.

4 Likes
#43

He dose not have a brain.

This person is shot, he is attempting to commit suicide by chemical injections.

#44

I am well aware rapa is not a risk free drug. As far as that equivalence u get when taking it with ketoconazole is not necessarily that simple and equivalent to the as high of doses u quote in every way. In any event your multiplication factor used with ketoconazole is way too high. As i have read the multiplication factor is less for injections compared to oral. And for injections 200mg keto… gave at most a 3 to 1 ratio factor as i recall in reading. A couple or so times i forgot to take the ket… and as i recall one of those times after 2 or 3 days i noticed about the highest exacerbation of side effects mainly mouth sores ever. And if you have read all the posts here and the articles they quote and attach then i don’t know how many times it is stressed that overdoses of rapa are usually NOT serious or some words to that effect atleast for those with no disease - have read like that at least 4 different places and some cases they were speaking of over 200mg. I know it suppresses immune system as i have witnessed. i would not attempt nanoemulsions as it is just too difficult and requires some ‘exactness’ etc. And as far as a prior comment about …not using iso-propanol for injections i am afraid u are wrong. For example just google
’ Rapamycin-Loaded, CapryolTM 90 and Oleic Acid Mediated Nanoemulsions: Formulation Development’ though u could likely find the article with less words. Anyway just read that article and u will see they are always using iso-propyl and not ethyl. and i am sure there are many more instances of using iso-propyl in other injections. And now i cannot believe how nit picky one can possibly be - afraid to inject isopropyl rubbing alcohol from wal-mart in small percentage with other substances. Would not even think twice about something of that high of purity as wal-mart would have for rubbing alcohol with nothing else but water ! you are talking about a multi-billion dollar company with very high credentials ! You can be nearly 100% sure they are not going to put anything the least bit harmful in that to be done topically or injected in small percentage with water for example.
How did i arrive at 20 to 30mg injection. For one from the published mouse studies articles periontally(maybe spelling error) injections which showed the most impressive results at 10 to 15mg per kilogram. Using the published 12.3 factor for mice and rats compared to human then that translates to around 1 mg per kg for human and i am like around 70kg so i should be using 70mg and what’s more than that the mice/rats were getting that every day not just every 5th day. Ok for that formula you wrote for one you did not define the parameters or whatever such as K,D,Vd,r,t nor the subscripted. Anyway i would very much doubt that over 95% of doctors would not be familiar with that on the fly’ (eg perhaps double negative incorrect grammar but think u know what is meant) “How the F did you come up with that math? Sensible probabilities? Brother, you don’t even know what you’re doing to your own body.” that could likely be true but neither does anyone else know either. If it was even 10% as bad as what these posters proclaim then i would be a hell of a lot worse off than i am of which as far as i can tell is about average normal aging.

Anyone trying something a little more edgy?
#45

only put them in the capsules right when u are ready to take them. Even though acid resistant they are still fragile so don’t store them for any any long time - like less than an hour for sure unless u know otherwise.

#46

Yes, thats exactly what I’m doing. Keeping the solution in a dropper bottle in the fridge and making up a capsule for immediate use. So far so good. One or two minor side effects as I’ve been very slowly increasing dose - only just reached 5mg/week.
Good thing about having some rapa in solution is that its been very convenient to add to moisturiser cream and toothpaste.

1 Like
#47

Please don’t listen to Dan’s advice.

This man injects himself with non-sterile tap water from the Philippines, rubbing alcohol literally from Walmart, and has abused more drugs than I can list in the goddamned USP formulary.

If you want more accurate advice, I’ll give you a breakdown:

Most capsules sold on the market to consumers is not of pharmaceutical grade. In other words, when they are marketed as being enteric coated (meaning they resist bile acids and allow the capsule to pass into the small intestine), they don’t actually achieve this.

Enteric coatings are tightly regulated by the FDA in the US, and by the EU’s equivalent in Europe. As such, only licensed pharmaceutical vendors can acquire and/or manufacture true enteric coatings.

You can test this by filling your capsules with a colorant such as food dye and submerging it in vinegar. If it dissolves in less than 2 hours, or if leaking is visible, it’s no good.

Furthermore, there is a reason why you don’t see many enteric coated capsules sold by pharmaceutical companies - which is that they tend to float rather than sink. Almost all use the enteric-coated tablet form for that reason.

Your strategy of putting a size 0 cap into a larger 000 cap, assuming the 000 cap is truly enteric-coated (which it is likely not), may stay afloat in your bile acids rather than sinking due to entrapped air. Again, you’d have to test this yourself, and you might need to pack the pills with some filling powder in order to make it sink. Also keep in mind that stomach fluids are quite thick, so what sinks in water may not sink in such fluids.

Furthermore, you should not store your rapamycin solution in a fridge, but rather a freezer. This will better preserve your solution. In addition, the shelf life of rapamycin in solution is much shorter than in dessicated powder form, another reason why pharmacy prefers the tablet form. If you continue with the liquid form, be cognizant about making batches in small volumes and using it up fairly quickly.

Ultimately, I think you may not be receiving the full rapamycin dose that you intend with how you are preparing the capsules. You might want to explore creating tablets at home with your own enteric coating. I can provide a guide on that if you’d like to know, but be warned that purchasing equipment to make tablets can get you into trouble with the DEA, which is why I don’t readily post information about it. There are ways around this, however.

P.S. Yes, I recognize the absurdity that the FDA/DEA regulates tablet presses more so that injectable formulations. AFAIK, it’s because tablet presses can “mass-produce” pills for distribution, whereas injections aren’t easily scaled up like that.

4 Likes
Rapamycin for my Cats?
#48

Thanks for all that. Yes , I did wonder if the capsules would float!
Ultimately I think I’ll end up buying enteric coated pills at some point in the future.
For the time being I’ll use my existing supply, slowly increasing dose and understand that not all of this may be getting utilised.
I will however try storing the solution in the freezer. I was concerned about solubility at low temps but will try with the next batch.
Also may try packing the gap between capsules with sodium alginate as an additional protective measure!

1 Like
#49

Hey, that’s a neat idea!

Assuming you can pack each pill tightly, you could put a smaller size 0 capsule (with your rapamycin), pack the 000 pill lightly with sodium alginate, and then press and compact the size 0 capsule into the size 000 capsule.

This might actually create an enteric capsule, even if the capsules themselves are not enteric! Alginate is being used now as a natural enteric coating alternative to the usual artifical plasticizers.

In any case, here is a paper I’ve found regarding sodium alginate being used as an enteric coating. However, it seems to be a paper directly from a private company, and it doesn’t seem to be published in any journal, so I’m unsure of its legitimacy.

And there does seem to be a patent on a sodium alginate and shellac solution for enteric coatings:

In any case, sodium alginate is much easier to source and work with than food-grade shellac, so this is quite exciting to me.

4 Likes
#50

For your information I have now bought ethanol 95% from Philippines as they don’t put any or not as much extra ‘duty’ on it as in usa which makes it quite more expensive here. NOt to say isopropanol was any problem. I am sure those who wrote that article were aware of ethanol but they found isopropanol better for that particular case and if they had any inclination that isoprop… was too toxic or etc. they would have mentioned that. I am even considering going to oral myself because of eg. at best ‘sterile abscesses at injection site’ .See article
‘Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs’ NOt to say that all mine were sterile as atleast one or more in philippines were NOT sterile but likely not sterile but infectious. Those articles that proclaimed better than rapamune were NOT homebrew but professional ::Solid Sirolimus Self-microemulsifying Drug Delivery System: Development and Evaluation of Tablets with Sustained Release Property , another 'Optimized formulation of solid self-microemulsifying sirolimus delivery systems ’ and The influence of co-solvents on the stability and bioavailability of rapamycin formulated in self-microemulsifying drug delivery systems ’ All of those show better than rapamune eg the last says "AUC (i presume means area under curve?) values…than those of Rapamune. Does it mean or did i imply I can formulate as in home brew, NO very likely not esp doing things the way those pro’s do. Especially i cannot do microemulsions either as they are quite critical and difficult even for pro’s.