Icariin - A promising treatment for various cancers, neurological diseases, and more, and a possible treatment for my uncle

Ground Up
1

What is Icariin?

Icariin is a major bioactive pharmaceutical constituent isolated from Chinese medicine Horny Goat Weed. It is classified as a prenylated flavonol glycosid. It has a wide range of potential applications in preventing cancer, cardiovascular disease, osteoporosis, delaying the effects of Alzheimer’s disease, treating erectile dysfunction, etc

My situation

My uncle was recently diagnosed with stage 3 pancreatic cancer and I've been looking for any way I can help. For a long while before the diagnosis I've been interested in icariin for it's wide array of therapeutic applications. Now, I have a family member in immediate need who could benefit from it. So, I've decided to post about it here on F4200.

Why I post here

I see this forum as a community of incredibly bright, talented, and kind people, and I think many of you may carry the knowledge (and equipment) needed to create icariin formulations with optimized bioavailability which my uncle and many others could benefit from. Some of you create nanoemulsions with Delta 8 and other cannabinoids to improve water solubility and I think something like that is exactly whats needed to improve icariins bioavailability.


I want to help in any way I can, and at the very least I hope this thread can begin the discussion around an incredibly versatile substance that could improve millions of lives.

A couple applications of Icariin

--- Cancer ---

--- Neurological Diseases ---

Alzheimers , Parkinsons, ischemic stroke, depressive disorder, multiple sclerosis, glioblastoma, hereditary spastic paraplegias

Poor bioavailability and improving it

To my understanding, a major roadblock with icariin is it’s poor bioavailability. So, in order for this to be a viable treatment, it’s bioavailability must be improved. There are many existing strategies to accomplish this which you can read about here: Bioavailability Improvement Strategies for Icariin and Its Derivates: A Review

In this study Development of an Icariin-Loaded Bilosome-Melittin Formulation with Improved Anticancer Activity against Cancerous Pancreatic Cells they improve bioavailability through a formulation with bilosome salts while possibly imrpoving effectiveness against cancer cells by including melittin. This may be the optimal solution, but I believe many of the bioavailability improvement strategies in the literature review mentioned above would be quite effective on their own.

Going forward

If we could create one of these bioavailaibilty improving formulations, the general public would benefit greatly. Are the strategies used to improve icariin's bioavailability at all similar to the nanoemulsions people are performing with Delta 8? and if so is it possible someone could help me create one of these formulations? It'd be a godsend
10 Likes
2

Do you’ve the compound with you, in its pure form? If it’s a pure compound, something can be tried. If it’s in the form of an extract, it’ll be difficult.

1 Like
3

98%+ icariin extracted from epimedium is attainable. Is that workable?

4

Yes. I’ll send you details on DM.

5

Best wishes to your uncle. You’re a good nephew. :peace_symbol:

From glossing over the first study you shared, the bioavailability issues seem similar to those of cannabinoids.

A monoglyceride carrier oil would be a good choice for nanoemulsion, SEDDS, etc. (a microemulsion wouldn’t be a good choice). Specifically, one rich in long-chain triglycerides with a very low HLB (extremely low water solubility). For example, winterized glyceryl/glycerol monolinoleate like Maisine CC. Additionally or optionally, LCT vegetable oils are commonly used to increase bioavailability by reducing first pass metabolism and increasing emulsion stability by impeding Ostwald ripening; organic high oleic sunflower is an optimal choice and is easy to source. Along with other bioavailability enhancers, and without knowing anything about icariin, piperine, curcumin, and resveratrol could be examples.

Particle size matters, so for a nanoemulsion using minimal dispersed phase (<10%) microfluidization, HPH, or UHPH would be best (going for the highest possible pressure). HSM (high shear mixing) using a high shear rotor-stator is an option, but it’s challenging to achieve <50 nm particle size with <0.2 PDI and long-term stability when relying on natural emulsifiers. It’s not impossible with HSM; it just takes proper formation and preparation.

A non-aqueous nanoemulsion could be a good option rather than an O/W nanoemulsion. Placed into a dopper and added to a beverage for administration because when adequately formulated, they retain their nanoparticle size when diluted. This isn’t the same as SEDDS because those only form <50 nm particles once diluted into bile and lighted agitated by the microflora; plus, SEDDS typically require a considerable concentration of synthetic emulsifiers.

Some studies worth checking out, there are many others you could reivew:

Development of a Novel Nano­emulsion Formulation to Improve Intestinal Absorption of Cannabidiol

6 Likes
6

Do you have homogenization and lab equipment?

7

I don’t. What equipment is needed to create nanoemulsions? I have a lab close to me which specializes in nanoemulsions of cannabinoids and terpenes and I’ve been talking to them, but the lab manager is pretty busy as is so any progress is slow

I’ll do my best reading the studies, but it’s difficult for me to gain meaningful knowledge from them due to a lack of background in chemistry / biology. Do you have any recommendations on reading material to help me better understand them?

1 Like
8

Considering your uncle is stage 3, without knowing if the tumor is regional, resectable, or its classification, he may not have time for you to learn these topics. Even for me and people with greater knowledge and experience, these topics are complex, and much R&D is required to optimize the final products. So the aphorism “perfect is the enemy of good” should probably dictate your course of action.

In other words, it’s probably better to have a product that will provide the icariin with some bioavailability improvement, even if it’s not optimized, because some is better than none. And once you start the icariin treatment, the delivery method can be optimized while treating him with the ‘good enough product.’

First and foremost: did you discuss your plan with your uncle and his doctors? You want to ensure that icariin and the product you wish to make aren’t contraindicated.

Because I empathize with you and your wish to help your uncle, and it’s in my nature to help someone suffering, I would be honored to design an icariin nanoemulsion for your uncle for free. With the primary goal of now, not later, as a ‘good enough’ formulation and SOP based on HSM processing. Other high-energy homogenization methods are superior but are significantly more expensive, with a greater learning curve.

If you’re interested, I would initially choose easily and quickly sourced ingredients that will significantly increase the bioavailability of icarrin while producing a stable product. Ideally, by working with your uncle’s doctors to ensure the ingredients don’t concern them. After that, if you are willing to do R&D testing, I would work with you to optimize the nanoemulsion for even greater bioavailability and reduced onset time.

You only need $2-3K and 2-3 weeks to make this project a reality. The 33,000 RPM Cat X 1000D high-shear homogenizer and T17 shaft with fine rotor-stator (60426-000F) is an ideal choice for cost savings and <200 nm droplet size. The greater diameter of the 60426-000F provides more significant turbulence and shear vs. the 60423-000F, providing for smaller droplet size. You can purchase that setup from the mfg for about $1,300, including shipping (which takes five days).

If you cannot afford to spend that much right now, maybe @QMA would loan or rent you an X 1000, and you can buy a shaft and fine rotor-stator (~$600 incl. shipping from mfg). AFAIK, @QMA only has the viscous rotor-stator, which isn’t deal for nanoemulsions. Another option is to buy the used X 1000 listed in the classified section by @Eastcoaststrange. But the asking price of $1,200 is high, considering you can buy a brand new X 1000D for ~$1,300 (including shipping). Maybe @Eastcoaststrange would be willing to come down on the price, accept payments, or loan the unit to you.

You also need a heated magnetic stirrer plate with thermo probe, cheese pH meter (e.g., Apera or Hanna), tall form beakers, accurate 0.01 g scale, and class A graduated cylinders. Nice to haves include an overhead mixer (min 5,000 RPM) with a high shear sawtooth impeller and 250-500 mL sep funnel.

I believe that health care is a human right and shouldn’t exclude people without means. So, my only requirement would be an NDA and a contractual agreement that you wouldn’t seek to monetize my work. If it’s efficacious, I would file a PPA and then open-source the project. The PPA would help prevent others from attempting to monetize the work (stronger than claiming prior art). And open-sourcing the project would allow anyone to make it themselves, including people in counties lacking high-quality health care.

9 Likes
9

He is selling a kit that would cost ~2200 new. I hate how @goldleaf_scientific markets their motors by themselves, as customers still need to purchase rotors (~$7-800 dollars) stands (~$100) and tools (~$100)

1 Like
10

I wasn’t referring to GoldLeaf. I’m talking about buying from Cat in Germany:

  • Stand and cross-over clamp $205.07
  • Both wrenches $57.55
  • X 1000D motor $733.76
  • One shaft and stator $426.25
  • Five-day shipping and export fees $202.63
  • Total is ~$1,625.26

Sourcing the stand and cross-over clamp from amazon for ~$60 reduces the total price from Germany to $1,479.56.

Without shipping, just the motor and one shaft/stator are $1,160.01 directly from Cat. Including shipping the total is $1,362.64.

Would you be willing to accept payments, or rent or loan an X 1000 homogenizer motor to @TraphouseFish for this project if he cannot afford to buy a unit outright? That way he could get the motor from you and buy the correct shaft/stator from Germany.

11

Unfortunately, neither I nor Cat Ing have any motors or shafts in stock. Even so, I would not loan out the motor or shaft as it is not the right tool for the job, as you noted previously. He would be better off with a sonicator.

12

Daniel from Cat didn’t mention a lack of stock last week. So I assume they have stock now. Maybe you’re referring to a previous lack of stock?

Rotor-stator HSM is undoubtedly an acceptable method to create a nanoemulsion at <200 nm; or even <100 nm, although that’s difficult. It’s all about selecting the correct stator (narrow slits as possible and the widest diameter), a suitable motor (highest RPM), proper formulation of the NE (which I won’t go into detail about here), and optimized SOP.

For this project, it’s the best option due to its low cost and ease of use for a suitably bioavailable icariin or cannabinoid NE. It’s true that microfludizaiton, HPH, or UHPH would be much better. Still, the rotor-stator will work well to get the job done, considering the time constraints with a guy who may otherwise die within 0.5-2 years.

Ultrasonic isn’t an optimal choice for NEs in most situations. USH is typically selected because it’s cheaper than microfludizaiton, HPH, or UHPH, especially at scale. Ultrasonic is like the halfway point between HSM and high-pressure methods.

13

He may have not mentioned it, but that is because of his shortcomings as a supplier. I would know as I have orders that have been sitting paid and undelivered since august. Check your invoice for delivery date and add 3 weeks to the estimate.

Come check my work in a dm with @anon56994712.

1 Like
14

Thanks, I will email Daniel to inquire about the delivery date. The invoice shows a delivery date five days after the purchase date.

No need to check your work; I trust your word about the lack of stock.

15

If there is any rush I can assure you Daniel from CAT is not the way I am 5 weeks out on a little 300$ dk30

Ralf would any of these fit his requirement? My connection in China recommended this factory to me

1 Like
16

Why would he need to produce the final product? You have already stated the you would be willing to help. I (and many others) would be more than happy to produce an NE for him free of charge if he is able to source the input material. It seems our focus should be less on equipment acquisition and more on material acquisition.

4 Likes
17

Damn, that’s a while to wait for the DK30. Sorry to hear that. Thanks for the link! That lab scale homogenizer wouldn’t suffice because the RPM is too low, and I’m unsure of the slit sizing. But Chinese high-shear is a great idea.

It was under the assumption that he would have to produce the emulsion himself. It would be fantastic if you or others made it for him!

I would, but my lab is broken down right now, so I can’t make the product. I agree that the focus should be on getting the materials and formulation, not equipment.

Even better if someone willing to help has an ultrasonic or high-pressure system! The high-shear suggestion was to save him money and time (if he had to source the funds), assuming he would make the product.

18

What’s the product consist of? I have lab hot plates, x1000, x1740 and sunflower oil

2 Likes
19

Like your generosity, my thanks for you are endless. I have not yet discussed it with my uncle or his doctors because until you’ve started responding I could’ve only hoped to make this possible. Thank you for changing that

I’ll talk to him about it within the next few days but it’s a bit difficult because I’m in Norway and there’s a large time difference. He’s not going to move forward blindly, so I’ll have to read over the studies again. Depending on what he thinks we can open a line of communication with his doctors then hopefully you can work with them to ensure the ingredients don’t concern them and we can move forward onto R&D.

I think I could put the money together to buy or rent the equipment, but ideally we could work together with someone who already has it. Either way I’ll do whatever is in my power to make this happen. An NDA and contractual agreement are totally fine by me, I’m not looking to profit off this medication. I just want to help my uncle and the many others who could benefit from it’s use.

In the meantime until I talk to my uncle about it I’ll be sourcing the icariin. Currently I know LiftMode and many suppliers in China carries (allegedly) 98% icariin. Do you have the capability to test the purity of icariin samples via HPLC or some other method?

1 Like
20

Just icariin and whatever carrier is used. Optimally we would also include melittin (see here).