DIY Rapamycin Toothpaste and Flossing Paste

[RapAdmin]

This post is to continue on the theme of the Do it Yourself (DIY) type of effort that was documented in the rapamycin skin cream post: DIY Rapamycin skin cream

and has been initiated because of this research: New Study Funded: Towards reversing periodontal disease using Rapamycin

Following is my overview of the step by step process I used for creating my rapamycin toothpaste and flossing paste (my plan is to dip my floss sticks into the formulation prior to flossing, and then I will brush my teeth with the same toothpaste formulation).

Periodontal disease (periodontitis) is a chronic oral disease impacting over 70% of older adults, where inflammation of the tissues supporting the teeth results in loss of connective tissue attachment, bone, and ultimately the tooth. The greatest underlying risk factor for periodontitis is age, and its association with other age-related diseases, such as heart disease, diabetes, and even muscle loss, and alzheimers disease, strongly suggests the importance of oral health.

I’m trying this, based on the research done previously on rapamycin and oral health: New Study: Rapamycin Rejuvenates Oral Health in Aging Mice

And, because of the new clinical trial trying to further increase oral health with topical rapamycin toothpaste, etc, as outlined in this new initiative: New Study Funded: Towards reversing periodontal disease using Rapamycin

My plan will be to check with dentist measures of tooth pocket depth and compare over time, pre and post treatment.

Step 1. Gather up the Ingredients and tools.

Total Time requirement: 10 minutes to 15 minutes
Total Approx. Cost: $23.90
Rapamycin: $10.00 (at specified dose. This can vary significantly depending on dose)
Toothpaste: $11.90
Transcutol: $1.00

Ingredients:

• Rapamycin (I used 10 X 1 mg zydus sirolimus tablets). Note: This dosing of 10mg rapamycin to 100 gram total solution translates to .01% rapamycin dosing. Nobody currently knows the “right” dosing yet and people are trying from .01% all the way up to 2.0%. Anywhere in this range is a reasonable place to start. I started low dose, partly just because I wanted to get going on this effort and don’t have lot of rapamycin on-hand right now. When I have more rapamycin I’ll likely increase the dosing to 1.0%, or 100mg rapamycin per 100grams of toothpaste.
• Transcutol (DEGEE)
• Toothpaste (93 gram jar of toothpaste for easy removal, mixture and replacement of toothpaste)

Tools:

• Mortar and Pestle for crushing the tablets
• Mixing Tool / Stir tool (power tool/cordless mini mixer)
• Mixing Bowl (note, a smaller mixing bowl would be better than the large one I used, as shown)
• 5ML Measuring Test tube (or other measuring device)

Step 2. Crush Tablets

Step 3. Mix powder with transcutol

1. Measure out approx. 5ML to 10ML of transcutol
2. Poor into mixing bowl, add powder from Mortar / Pestle bowl
3. Mix thoroughly (approximately 5 minutes of mixing).
   There are some small white flecks from the surface material of the tablets. I ground those up as much as possible in the mortar/pestle and then again in the mixing bowl with the powered stirring tool. I don’t care too much about these small white flecks, as I think they are not the active part of the rapamycin tablet, just the external coating.

Step 4. Take toothpaste out of jar, put into mixing bowl with transcutol mixture, and remix formulation

I scooped the toothpaste out of the jar it comes in, and placed the toothpaste into the bowl with the transcutol/rapamycin mixture. Then began mixing the combined solution with the cordless mini mixer.

Note: the inexpensive cordless mini mixer tool really had problems with the thickness of the toothpaste. I would not recommend this product; its the cheapest Amazon.com power stirring mini mixer tool that I could find, and it performs as such. It would be fine for the skin cream mixing, but not the toothpaste formulation. I ended up mixing it initially with a spoon, and then after the transcutol mixture was reasonably well mixed with the toothpaste the solution was lower viscosity and could more easily be stirred with the power stirring tool. Still, not an ideal tool for this.

Step 5. Scoop the new Rapamycin Toothpaste mixture back into original Toothpaste Jar

Use the spoon to again scoop up the well-mixed rapamycin toothpaste mixture and put it back into original toothpaste jar. It should fit without a problem. I used a rubber spatula to do the final collection of the toothpaste from the bowl, and transferred it into the jar.

Sources of all the ingredients and tools used in this DIY formulation:

Rapamycin Sourced from: 在线购买雷帕霉素 - 可靠药店列表

Where you can order / buy Transcutol :
LotionCrafters: Transcutol / Ethoxydiglycol
Laballey.com: Transcutol / Diethylene Glycol Monoethyl Ether

Jar of Toothpaste

https://www.amazon.com/Nelson-Naturals-Spearmint-Fluoride-Toothpaste/dp/B079G8NTF5

Mortar / Pestle

Amazon.com: Tera 18/8 Stainless Steel Mortar and Pestle with Brush,Pill...

Mixer

https://www.amazon.com/Badger-Air-Brush-Co-121-Paint/dp/B000BROV02/

The one below is what I used, but it was not a good solution for mixing the thick toothpaste:

https://www.amazon.com/dp/B06XHLPZ45/

Measuring Cylinder / Testtube

https://www.amazon.com/ULAB-Scientific-Measuring-Hexagonal-Graduation/dp/B07FDXQCMX/

https://www.amazon.com/4oz-Graduated-Cylinder-Measuring-Versatile/dp/B094CCXPTJ/

Transcutol Safety Background (oral and topical applications)

Transcutolsullivan2014.pdf (369.6 KB)

[TimePie]

@RapAdmin

Transcutol

I’m kind of curious. Why do we use transcutol here?

[RapAdmin]

I used transcutol because its a well proven and frequently used solvent/excipient for mixing of drugs being used topically, and even in food ingredient manufacturing. Rapamycin is also very soluble in Transcutol so will disolve well, and it seems safe, and effective. And it improves the absorption of the drug into the skin. I saw it referenced frequently in a number of applications for topical skin / drug formulations.

And I have a half-liter of it left over from when I made the skin cream, so I thought I’d use it here also.

Just mixing the rapamycin powder into the toothpaste by itself is obviously an option, but I thought its probably going to be more effective (at penetrating my gums and around my teeth) if I mix the powder by disolving it in a solution (the transcutol) thoroughly, and then mix that liquid into the toothpaste thoroughly.

There is also the issue that in any given 1mg tablet of rapamycin / sirolimus most of the tablet is filler, etc. If I just powdered the tablet and mixed that powder into the toothpaste I think the 1mg of rapamycin would likely be clumped together with the filler, and not well distributed in the toothpaste, for maximum benefit to the teeth and gums. The rapamycin is quite soluble in transcutol, so I think it and most of the filler, with good mixing, likely disolves well (and this does infact seem to be the case in my two times I’ve done made rapamycin/transcutol mixtures) and then is easier to mix well with the toothpaste in the final mixing step.

And - I’ll use the rapamycin toothpaste on my toothbrush, and also dip my flossing sticks into it before I floss at night. This seems like the best way to get the best penetration. Of course, at the end of brushing and flossing I spit out most of the toothpaste, so I’m not too concerned about ingesting much of the transcutol.

I’m not a compounding pharmacist… so take my opinion on this with a grain of salt, and hopefully someone with more knowledge than I can confirm or refute this approach and information.

From one other paper:

We then assessed different safe ingredients usable for topical application. Table 1 shows rapamycin solubility in three ingredients. The best candidate was Transcutol® that solubilizes rapamycin extemporaneously, whereas the drug was only slightly soluble in other ingredients. Transcutol®, i.e. diethylene glycol monoethyl ether, is already used in marketed medicines. Furthermore, Transcutol® has been shown to be a drug penetration enhancer in the skin (Mura et al., 2000). This property appeared very interesting to exploit, as it could improve treatment of angiofibromas. The rest of the study was therefore performed with Transcutol®

Source: Formulation and characterization of a 0.1% rapamycin cream for the treatment of Tuberous Sclerosis Complex-related angiofibromas - PubMed

Excipient

[EnrQay]

I wish I had done that gum pocket depth measurement before I starting using my rapa toothpaste about 6 months ago. Good idea about using it with flossing–I haven’t done that yet.

I have used a rapamycin proportion similar to what has used in Dr. Green’s skin cream and the transcutol at 2%, similar to what I saw in skin products. This meant I used double the rapamycin you used and about half the transcutol. How did you decide on the ingredient proportions?

The white flecks can be eliminated by putting the powdered rapamycin through a tea strainer, with almost no loss of powder. This is especially useful for the rapamycin skin cream.

[RapAdmin]

@EnrQay

How did you decide on the ingredient proportions?

Most of the topical rapamycin creams I’ve seen papers on used pretty low dosing, .01% to 1.0% rapamycin by weight. So, I went on the low end of the dosing. part of this is simply because I wanted to get going and I don’t have a ton of rapamycin on hand right now so didn’t want to use it all up in one shot here. Plus, I can always add more rapamycin to the toothpaste later if I want to.

Typically they use 5% transcutol by weight in solution formulations - so I was targeting that, but then the toothpaste was so thick and difficult to mix with that I decided to increase the transcutol to make the entire solution a little more fluid and easier to mix.

So - tell me how many tablets / mg of rapamycin and the total volume of toothpaste used to make your formulation. Obviously - there is no hard and fast rules here right now - we’re all just testing things out to see if the animal research translates to humans. Now that you bring it up - I’ll likely increase the potency (rapamycin %) of the toothpaste when I get my next shipment of rapamycin.

[EnrQay]

28g toothpaste + 0.01% (3mg) rapa + 2% transcutol (0.6g). I might go to 5 mg rapa in the future based on Dr. Green’s skin cream recipe. See

New Study Funded: Towards reversing periodontal disease using Rapamycin

Me. I’m going to mix up a small batch at 0.01%. I picked this percentage based on the higher level in Dr. Green’s skin recipe of about 0.016%. Since we are talking about mucus membranes in the mouth, I figure absorption would be better, so lower the %. If I am doing my math right today, a 3.5oz (almost 100,000mg) tube of toothpaste would need 10mg rapamycin

[shc]

Any thoughts on using DMSO instead of transcutol? The latter is a bit hard to find right now for me.

[RapAdmin]

Sorry, I don’t know much about DMSO, and have no experience with it. Perhaps people here who do can add their thoughts. Or, do some google research on what has been published in terms of using DMSO for oral / topical applications.

[shc]

Alight, thanks I’ll look into it and report what i find. I just presumed that you’d considered DMSO as well and decided against it for a reaso.

[RapAdmin]

@shc

I just presumed that you’d considered DMSO

No - I was making some rapamycin skin cream and read this paper below and it mentioned transcutol as a good excipient/solvent for rapamycin, so I purchased and used it. And I’m just trying to repurpose the 500ML I still have left. I have not done a comparison between DMSO and transcutol.

Formulation and characterization of a 0.1% rapamycin cream for the treatment...

[Sassenfeld]

Great article, thanks.
Where do you purchase the transcutol?
Helmut

[Pat25]

Same question as Helmut: where to buy the Transcutol? Has any member in Europe been able to find a source to buy Transcutol?

[RapAdmin]

@Sassenfeld

Where do you purchase the transcutol?

I assume you saw the pointers above to some transcutol sources in the US, so you must be outside the US. Here are all the different identifiers / names for transcutol. Googling on the CAS # might be helpful, or any of the other names:

Transcutol has a number of different chemical names/identifiers. Here is a list:

• 2-(2-Ethoxyethoxy)ethanol: Ethoxydiglycol, 3,6-dioxa-1-octanol,
• DEGEE, diethylene glycol monoethyl ether,
• Carbitol,
• Carbitol Cellosolve,
• Transcutol,
• Dioxitol,
• Polysolv DE,
• Dowanal DE

Chemical Identifier: CAS Number 111-90-0

Examples of Where you can order / buy Transcutol from in the USA:
LotionCrafters: Transcutol / Ethoxydiglycol
Laballey.com: Transcutol / Diethylene Glycol Monoethyl Ether

[Bicep]

I’ve used DMSO quite a bit for arthritis and have “The DMSO Handbook for Physicians” Lol, good luck finding a doctor that will work with it.

Anyway it says to use 30% to 50% solution (with distilled water) for mouthwash or brushing. You’ll want to dissolve the Rapa in the pure stuff. It will be a solution about like water, so I would get a spray bottle of some sort and spray it onto the brush. I would try this tonight, but don’t know how much Rapa to use.

How much will be absorbed in the mouth with DMSO? How much is safe? Should you do it daily? I’m not worried about the DMSO at all, just the Rapa.

I had a molar pulled about a year ago and packed cotton swabs with 50% DMSO into the hole. It healed right up.

[Jay]

Hmmm … that sounds interesting. I usually rinse after brushing. I wonder if mixing rapamycin with my rinse solution would be just as effective?

[LaraPo]

I was also thinking about it. If it were possible to dissolve rapamycin completely in rinsing solution, it could be used with water pic to reach deep pockets.

[Jay]

LaraPo, Of course, there is the solubility problem to be dealt with if using a rinsing solution.

[LaraPo]

Sure that some genius will figure out how to do that. Waiting…

[RapAdmin]

@Jay

solubility problem to be dealt with if using a rinsing solution.

I think if you first dissolved the rapamycin in transcutol, then mixed the solution with your rinsing solution (and I love the idea of using it in the water pic) - it would work well.

[CTStan]

or ethanol:
“DIY mouthwash: The Discovery Channel show “MythBusters” confirmed that vodka can be used as a mouthwash .”

Mythbusters Vodka myths