#12

Update:

I gave David Weinstein, the founder of Rivertown (now at Apellis Pharmaceuticals), a call to talk about what happened at Rivertown. He’s a very genial and talkative fellow and was happy to answer my questions and very enjoyable to discuss this with. (we ended up going on a long tangent discussing rapamycin).

He said the key issue was that it is very hard to get funding around a combination product (with generic drugs as key parts of the combination) in the cosmeceutical market space. I suspect that behind this may be the issue of how defensible any patent would be in this area, and of course the cost of large clinical trials is very significant to get FDA approval.

He said there is ongoing research with these compounds he is involved in (he is the PI) at the University Alabama which is also focused on hair color reversal, and he remains very confident about the results of this formulation.

David said that they had tested it with 40 to 50 people during the course of his efforts with Rivertown the past few years, and there were very high rates of efficacy. Anytime you stimulate the renewed hair cycle he said, you will get return of the hair color. Only if you have had a completely bald head for a significant period of time does he think it will not work at all.

The medical name for the process of hair going gray is, David informed me, achromotrichia. Put simply, ‘achromotrichia’ is defined as the absence or loss of pigmentation in the hair.

I discussed with David Weinstein the differences between the compound which he had identified in the lab (which only later did he discover had also been identified by Guilford Pharmaceuticals independently) and tacrolimus.

Tacrolimus, he said is very similar to GPI 1485 (GPI 1485 is actually derived of tacrolimus), but GPI 1485 is not an immunosuppressant. David said he was apprehensive around the idea of ongoing use of an immunosupressant even in topical form. (though in the study of topical rapamycin cream for skin aging, there was no systemic take-up of topically applied rapamycin, so I think his concern may be overblown).

David commented on how the research behind GPI 1485 (and what he saw) is that its very effective in increasing speed of wound healing. He commented on how tacrolimus, as an immunosuppressant, likely slows wound healing. So, he suggested while tacrolimus may have some of the same effects as GPI 1485, it also has some risks and downsides. So, in an ideal world, you probably want to use GPI 1485, if you can get it.

For people looking for this chemical, here are the identifiers:

GPI-1485

CAS No. : 186268-78-0

More on the molecule:

And David Weinstein’s research that led him, accidentally, to the hair formulation:

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#13

Did ITP ever test pulsed tacromlimus, cyclosporin or any other calcineurine inhibitors?

#14

No - you can see the list of tested compounds here:

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#15

I wonder if there is a synergistic effect. You know what I’ll get a tube of tacromlimus ointment and apply it to half my face and see what happens

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#16

RapAdmin, So, you used crushed pills and Transcutol only in your skin cream? I thought pure Transcutol on the skin would be too harsh, but maybe not. Do you mind sharing your exact formula of rapamycin pills and Transcutol in terms of milligrams of rapamycin and grams or ounces of Transcutol? And, you apply with a dropper. Does it spread smoothly? Do you wash your hands afterward. Yes, it does seem less complicated, but do you see any good results? Thanks for any response.

#17

Oh no - I started with raw rapamycin powder from a lab supply house, then mixed it with Transcutol (I forget exactly how much - a small amount, perhaps 20 or 30 ml). Blended that for a while in a metal bowl with my blender. Then added Cetaphil (or something similar) to the mixture - a large tub, approx. 500 grams), and blended that together in the same metal bowl for about 5 minutes to get it fully mixed.
When I was using the rapamycin skin cream - I’d apply it typically morning and evening, just like any moisturizer. It definitely has an effect - but its not life-changing (perhaps similar in effect size to retin-A creams).

I was just referring to the general technique more broadly.

Gray Hair Reversal Recipe

For the RiverTown anti-gray hair serum it will start the same (but I’m going to use tablets this time, not the lab-supply powder). Something like the following (I’m still working on this, will do a full writeup in the next week):

For a 100 gram (3.5 oz) batch of the formulation I think I’ll use something like:

  • 120 mg cyclosporin (approx. 5 of the 25mg tablets, powdered)
  • 500 mg of minoxidil (approx. 50 of the 10mg tablets, powdered)
  • 100 mg of tacrolimus (approx. 50 of the 2mg tablets, powdered) * note - this seems to be a mistake and too high - see details below in thread where the paper was corrected):

mix up in 20ml or so of transcutol, then add the other liquids to dilute it.
In the Rivertown formula they use the ratio: 50:30:20 of propylene glycol : ethanol : H2O.

I’ve had problems in the past with the topical minoxidil liquid mix causing scalp rash problems (not sure if it is the propylene glycol or the ethanol that is the issue) - so I’m evaluating other options and would appreciate any input here that people might have.

I might try just transcutol and see how it works on my skin as a first effort.

What might be some reasonable other options for mixing into the formulation? please comment if you have any ideas, and provide links to the literature that have made you think these other compounds might be good to replace the propylene glycol or ethanol for the hair serum.

General Hair Growth Serum Compounds

If you are very interested in the hair growth aspect (more so than just the gray hair reversal aspect) then you probably want to look at the minoxidil tablet successes that have been covered in The NY Times (Minoxidil Pills, An Old Medicine Grows New Hair for Pennies Per Day) and elsewhere recently.

And there are many other compounds that could be added to a hair growth serum that look like the have potential (and that have been discussed in depth in the "Rapamycin for Hair / Pigmentation / Skin anti-aging thread). These compounds for topical use include:

  • Rapamycin
  • Dutasteride or finasteride
  • Metformin
  • Tofacitinib
  • Ketoconazole
  • bimatoprost
  • ECGC
  • Rapamycin
  • valproic acid

Tretinoin (topical Mixture - Gel form) - this is a little more complex because I can only seem to find tretinoin gel that would work, not something I can readily mix with the rest of the compounds, so perhaps this needs to be a separate step / application layer.

And if you want to get really fancy, you could also do micro-needling to your scalp (with appropriate precautions). Micro-needling info here: Rapamycin-Loaded Microneedles Reverse Hair Loss in Mice

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#18

I have not done enough research to know about other options at this time. Will post if I find something.

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#19

Looking forward to your post after you formulate your batch. Which pharmacy do you prefer when your order is many disparate products along with your (preferably Zydus) rapamycin (I have a large order coming up with at least 10 different drugs for myself and family- many I have lazily just ordered from alldaychemist in the past, but their prices on many things are 2-4x what you’d get direct)?

You (and @Agetron too!) should really do a youtube video of your process making your concoction. You could film just the counter with your hands to preserve anonymity. For many of us (hand raised), watching somebody do this is infinitely more helpful/motivating than reading about it. Often I’ll read something and think “wow, this sounds complicated and difficult”. Then I’ll find a youtube video and it’s “that’s way easier than I thought- hell, I can do that”.

And, yes- the propylene glycol in the Kirkland (and all) topical minoxidil causes problems for a lot of people. There are people that sell minoxidil at 5x the price who compound it with something else for just that reason. Derek, the moreplatesmoredates bro-science entrepreneur sells it, among others.

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#20

I don’t have any preferred pharmacy, in fact quite the opposite, I spread my orders across all the different reliable online pharmacies so I get a feel for the different prices, and service level of the vendors. So far, they all seem pretty similar but prices vary significantly (but they seem to price based on perceived demand and supply).

Interesting idea about the video. I’ll consider it. I don’t have a video camera, so it would just be the cell phone - and I’m not sure that would be very good quality for a YouTube video. But, I’ll try when I do make the formula.

Regarding the replacement for the propylene glycol … good to know I’m not the only one who doesn’t like that. I’ve heard from others beside you also on this issue.

Alternative Excipients (to replace propylene glycol)

I’m going to look around and see what other groups use. I notice that the Formulation 82M that was mentioned in The NY Times article about Minoxidil tablets, has this formulation:

82M is a customized compounded prescription solution that contains the FDA-approved hair growth medication Minoxidil 5%, Tretinoin 0.01% for enhanced penetration and hair growth effect, the anti-inflammatory Fluocinolone 0.01%, an organic anti-androgen Oleanolic Acid and a sophisticated blend of powerful antioxidants, scalp conditioners and hair conditioners in a non-irritating propylene glycol-free base.

Source: Formula 82M - Compounded Minoxidil Formula - 3 Month Supply — Bauman Medical

I think I saw somewhere that this formula uses a product called “Trichosol” - but I may have seen it in another product. I’m looking at it as a potential replacement for the propylene glycol. See website here: TrichoConcept™ - Uni-Chem

I saw this comment on another forum:

Another option is Minoxidil in Trichosol, sold by Farmacia Andorra.

Trichosol is non-alcoholic solvent for hair medications, and it doesn’t have PG but it’s indeed minimally greasy due to essential oils. I apply trichosol with syringe or pipette directly onto the scalp and it’s cosmetically acceptable.

Formula 82F is similar:

82F is a topical compounded prescription solution containing the FDA-approved hair growth medications finasteride 0.25% and minoxidil 5%, as well as retinoic acid for enhanced penetration of minoxidil and sebum reduction, a mild low-dose anti-inflammatory, oleanolic acid—a mild anti-androgen, and other beneficial ingredients such as powerful antioxidant algae extracts without any propylene glycol (a common irritant) at a neutral pH. Finasteride is the active ingredient in the FDA-approved drug Propecia.

The website notes:

Why Compounded Minoxidil Formula 82M?

Unfortunately, despite the hair growth properties of minoxidil, the over-the-counter Rogaine, Rogaine Foam or generic versions can often come with unwanted side effects like itchy scalp, scalp irritation, sticky and oily or greasy residues that interfere with hairstyling and more.

How is Minoxidil Formula 82M applied?

Dr. Bauman recommends that at least 20-30 drops of Formula 82M should be applied twice daily to the entire scalp, focusing primarily in the areas of concern. For maximum effect, minoxidil should be spread evenly and allowed to absorb for at least three hours before showering, swimming or participating in heavy physical activity. A special ‘droptainer’ bottle allows for the accurate application of Formula 82M directly where you need it… on the scalp, not on your hair.

Formula 82M is a topical product that deeply penetrates the scalp with a blend of 5% minoxidil, vitamin E, biotin, retinoic acid, a 5-alpha reductase inhibitor, and several other active ingredients not found in over-the-counter formulas. This powerful blend of ingredients is capable of slowing hair loss and thickening hair.

The combination of minoxidil and tretinoin has been proven to increase the efficacy of minoxidil by increasing percutaneous absorption threefold. One study showed that tretinoin alone increased hair growth by 58%, while the combination of minoxidil and tretinoin increased hair growth in 66% of individuals.

Here is another formulation:

follikle formula

  • Finasteride 0.25%
  • Minoxidil 8%
  • Retinoic Acid 0.01%
  • Hydrocortisone 1%

Other compound ideas I’m coming across as I search the web: (Alternatives to propylene glycol) from the /Tressless subreddit:

ell-cranell, it has propanol, glycerol and myo-inositol in addition to alfatradiol.

My guess is that any kind of cosmetic solvent would do the trick and the solvent doesn’t react with finasteride chemically. How about glycerine or hyaluronic acid? I am guessing water would be too viscous.

KB solution or stemoxydine.

Minoxidilmax sells premixed RU solution without propylene glycol. Haven’t tried it yet but you might consider it

minoxidil and finasteride with trichosol in a compounding pharmacy is by far the best option in the world

you can check this formulation l, has PEG, but only at 5%.
https://www.reddit.com/r/tressless/comments/uj78ay/a_topical_finasteride_solution_for_those_with/?utm_medium=android_app&utm_source=share

Humectants by their very nature will make hair greasy. Glycerin will be somewhat less greasy than PG though

DMSO might be a little bit too effective without something like a humectant or oleic acid to keep the drug in the dermis a little longer. Speaking of, oleic acid might be of interest to you:
Oleic Acid: Its Effects on Stratum Corneum in Relation to (Trans)Dermal Drug Delivery | SpringerLink

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#21

Video from any relatively recent phone (even low/mid-range phones, not just flagships) is on par with, if not superior to, expensive stand-alone video of 10 years ago. Many are 4k (overkill for youtube), and ALL are 1080 HD - which is very good/normal quality for youtube videos.

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#22

I wouldn’t mind giving this a try. I’ve just started going grey, it might be interesting to see if it had any effect as it’s not too advanced.

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#23

In the mean time I’ll start doing half my face with tacromlimus ointment 0.1%. I’ll also make photos of my beard but I’ll let it grow out a bit more first

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#24

Any idea for a dosing schedule? Half life of the ointment is 65-75h and it has some nasty potential side effects one of which follicutitis I am already quite prone to… I think once a week seems like a safe starting schedule but might not be enough for the benefits either…

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#25

Good enough for an initial pic?

20220829_143146
20220829_143146858×1207 297 KB

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#26

In the published study linked to in the first post, they used this dosing schedule: “mice were gently shaved along their lower back and treated twice daily with the indicated solutions”

You’ll have to find a dosing schedule that works for you, if this type of schedule causes causes undesirable side effects.

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#27

Since the half life is quite long (75h) I think I will start with once maybe twice weekly initially for a few months. I can always increase the dose later.

#28

Yes - a reasonable strategy it to start more slowly and increase dosing if side effects are not a problem. One other consideration is how frequently you wash your scalp / face, etc. If you shower each morning, and it washes the formulation off your head each morning, perhaps application each evening makes sense. If you’re showering every 2 days, then perhaps every two days makes sense.

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#29

ok. I’ll take part in this challenge. I would love to fix my beard. It’s greying, and patchy… which is an awful combo. I’ll take a ‘before’ pic in the coming week, and I’ll come up with my final regimen by then as well. However, I won’t be taking my concoction twice a day… I tried that once before with minox 5%, and it gave me heart palps.

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#30

If you are already taking Low Dose Oral Minoxidil, any guesses on what effect might occur from topical application of cyclosporin and tacrolimus?

#31

I don’t know - I was wondering the same thing. Seems like a good example where a personal clinical trial n of 1 is appropriate. Make two versions of formulation - one with minoxidil and one without. Try each for a month or two and see if there is a noticeable difference.

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