Understanding Barrier Repair with Dr. Carl Thornfeldt of Epionce

26:02Do you think that that matters after a certain point? Or do you think that we need to have like more, I don't know, balanced formulations or like, you know, more holistic formulations? Yeah, I absolutely believe in the holistic is formulations are really important because what our goal in trying to understand all this was going on, as I said, we didn't set out for it to develop an anti-aging product. We set out to understand how the skin operates optimally and how it repairs itself from injury, how it prevents the diseases that occurred and occur as we age, which means that the skin, when it is insulted, it doesn't just strip itself off, do this massive exfoliation or anything like that.

26:44No, it starts triggering production of the three key barrier oils. It starts activating or inhibiting the chronic inflammation pathways with other signaling molecules. And it repairs itself gently and quietly. And then you end up with the supple skin and soft skin. So one of the fallacies is people think that, as I've mentioned, more is better. And that's not really the case, okay? So you need to have the optimum concentration. And as I said, there's no place in the body where a single antioxidant works. No, all the microenvironments, there's the combination of the multiple antioxidants. A matter of fact, five clinical studies with looking at different diseases, different types of cancers and heart disease, they found that high dose of a single antioxidant, including a study that was done with vitamin C, actually triggered increased heart disease and they stopped the clinical study over a year earlier because the increased incidence of the heart attacks occurred.

27:40They stopped the study on prostate cancer with selenium because the increased incidence of prostate cancer. They stopped the high dose vitamin A on colon cancer because the colon cancer rates went up. In other words, we have examples in the human body that have been published in not just dermatology literature, but in other literature clearly showing that high concentrations of a single antioxidant is in fact damaging. And that's not how they occur in your body. And there's over 8 ,000 compounds that in the laboratory have shown to be antioxidant effect. About 150 have actually been studied in humans.

28:16Of those, half of those showed minimal to mild benefit. The others, half showed no benefit at all. They actually showed increased toxicity. So that's the antioxidant story, but it's a kind of a dirty little secret that people don't want to talk about in the molecular arena. Although there have been a number of functional medicine doctors that have been reporting about how high-dose antioxidants in and of themselves or disease causing it. And that's absolutely been demonstrated in the scientific literature. Yeah, that's fascinating. I didn't know that. I mean, honestly, it's interesting now then to look at what is actually being marketed because we went from, for example, vitamin C to glutathione, which glutathione just never even made sense to me.

28:58Topically applying glutathione didn't make any sense. But we have an entire industry that's snowballing on these buzzwords that are coming from molecular biology and they keep doing it. And I just wonder, like, you know, when it comes to cell signaling, I'd love for you to speak a little bit more to our listeners about cell signaling, because this is something I wish people spoke about in terms of what cells actually interact with and how they actually respond. Because I don't think anyone really talks about that, you know, like in terms of like when you have a ligand binding to a receptor that elicits a response, what that means for all the other cells downstream, that's a whole conversation that never happens.

29:35So like when When we're thinking about the skin, what are some things that we should understand in that arena? First of all, with glutathione being an enzyme, when it's put on the skin topically, the various types of proteinases will usually destroy it. So it doesn't really get down to actually have any benefit. And it goes back to the green tea stories where they showed some benefit on the forums of elderly man, but no other place in the body have they actually proven that high-dose green tea extract actually works in reducing precancers and reversing photoaging. So that's a similar situation with the glutathione.

30:08And there are a lot of these ingredients out there that people are talking about, but they're looking at it from a lens of just a particular molecule. They don't seem to be thinking about how does it fit in the complex story? And then if you're going to modulate all these different signals, how do you actually do that? So I was excited to see the quorum type of technology being developed where that's how the cell interacts with the quorums. And now that they're actually have discovered these, that was a great breakthrough. So there are some raw materials that you can get that have some ingredients with that.

30:43But again, can you prove that it actually works and it works safely? That's what patients want. I mean, the problem with the whole vitamin C issue, one critical thing that people forget. And I went to Oregon State. Why is that important? Linus Pauling, the Nobel Prize for discovering vitamin C in 1954, happened to be a professor there. Okay. And so I know a lot about that. Okay. And he, in his original, when he would come back and give lectures to the chemistry department, he always talked about how the vitamin C, it's not just the L-ascorbic acid. You also have to have the ascorbate as well, which is very transient type of molecule.

31:21But to actually trigger collagen synthesis, you also have to have iron. And now we also know in the last few years, as has been shown, you also need to have some zinc as well to cause a synthesis of collagen. So you can put high doses of vitamin C on, but unless you got the iron component there, you're not going to get collagen synthesis. But people say, well, my wrinkles are better. Okay. Why is that? Oh yeah, you're getting irritation. You know, the original study that was published on vitamin C was published in the ENT literature. And the problem was one third of the patients dropped out because of visible contact dermatitis.

31:55Well, if you have a contact dermatitis, the wrinkles are going to look better. Skin's going to look more swollen. But the fact of the matter is of those patients who still completed the study, 65 % had erythema and edema. And they said, oh, well, the vitamin C works in wrinkles. Yeah, not really. Okay. It produced an irritation reaction. And what's going to happen with that? The chronic irritation reaction then triggers the matrix metalloproteinases to produce destruction of the skin and trigger pre-malignant cells and destroy the collagen and elastin, prevent barrier repair and a whole series of processes that occur from that triggering of the inflammation.

32:34And so, again, I think it's people are looking for a simplistic marketing piece of information rather than really saying, look, this is a complex organ system and you need to understand how all these things work and you need to understand how they work in formulation. And the only way you can tell that is, in fact, with double-blind, prospective, controlled clinical trials with a finished formulation conducted by a third-party research after it's been institutional review board approved with a statistically significant number of patients. Then you can tell whether or not it works because the odds are any type of herbal product or any other type of ingredient you put in 15 out of 16 times, it won't work.

33:15That makes sense. That makes sense. And this leads me to wonder because we had a movement of like natural-based skincare, you know, and plant-based skincare. And we still see that, you know, like I brought up exosomes a little bit earlier about how we're making plant exosome products, you know, and it's like, what is the purpose of this? Like what the skin is not going to react. So I'd love for you to speak on this idea of biomimetic ingredients for the skin and why that matters, because that's where I feel like the marketing, it's a snowball at this point, And it's like we just keep going down this road.

33:49So can you speak to us about that in terms of true biomimetic ingredients? Yeah, the biomimetic ingredients, they are claiming that because of certain structure and molecular makeup, that in fact they work identically to the way the human body does. And yes, it does depend on the specific molecule. But the question is, do the plant-based ones in fact actually have the same functionality? And the reason I bring that up is because one of the things that had always interested me was about the issue about why do basically plant extracts that are the tonics, why do they work better than the individual ingredients as you go down and fractionate it more normal and get it down to a couple of key hero ingredients, so to speak?

34:31Why do the tonics work better? Well, it turns out in plants, you have a group of compounds and elements that basically enhance the delivery and the stability of the active molecules. and those are called the entourage components. And as we did research in that, what we found is that the entourage components not only enhance the functionality and the stability of the main secondary metabolite, which is what the active ingredients are primarily in plants, but it also even increased it enough that there were additional abnormalities that were modulated by the entourage ingredients. And so I think one of the fallacies is that they're saying they're taking them from plants, but they are only using a particular molecule, which may have some variation in architecture enough that it's not going to be able to bind to the key.

35:22But certainly it does not have the entourage elements, molecules, and ions that are going to protect it and help maintain its stability. Consequently, there's a very rapid breakdown of many of those biomimetics because the metabolic pathways are there and they destroy it. But I don't see studies coming out actually looking at how are these molecules tabulized because your body needs to have a way to catabolize so you don't get buildup molecules, particularly when you're looking at like fat soluble vitamins and so on because then like vitamin A and vitamin K because you can end up with toxicity issues with that.

35:59So the biomimetics in my mind, they're claiming that it has this same kind of benefit, but from what our research showed in plants and what other very bright investigators have found, that in fact, it's not just the individual secondary metabolite, it's also the other components in there that allow it to provide that functionality. And to my knowledge, I have not seen anything in the literature that these biomimetics actually have those additional molecules to improve their stability. So you put them in, then you need to have a system to actually a delivery system to take it to the right strata.

36:33It has to target the specific cell. It has to be able to bind to the receptor in a proper way and sufficient enough to fully trigger functionality because that's the other problem. A lot of these biomimetics, they will increase functionality, but these signaling molecules have multiple steps like a tree that has the branches. And so there's multiple aspects of functionality they modulate And you've got oftentimes several different molecules are involved in producing a specific downstream pathway. And you need to have all those to work. It's like for pigmentation, there's 31 steps. And if you want to have something that's truly hyperpigmentation, and that's why things just inhibit tyrosinase or block one of the other two or three steps, which is all we do today, why would you expect to get complete clearance?

37:20100%. Yeah, it doesn't make sense. And this is so fascinating because it really opens up that conversation of how the skin is a very, very dynamic arena. Like you have to really understand all of the moving pieces. And, you know, one of the biggest questions I think that comes up is in terms of like, for example, retinoids. There's a lot of drugs in dermatology that I think they've been around for a long time, you know, and they're still being marketed and they're still being pushed as this is the one and done solution. But I know for a fact, like, for example, hydroquinone or tretinoin, they don't work for a lot of people, you know.

37:51And they end up causing a lot of other downstream effects that are then you need to manage those. So what is your opinion on that in terms of people, for example, if somebody is utilizing tretinoin for anti-aging benefits, photo damage control, how can we understand the true potential of this drug in our skincare routine versus just what we've been kind of marketed to for a long time? So, tretinoin was developed because they found that that was the final component of the vitamin A metabolic pathway that actually would trigger functionality within the skin and other membranes. So, that's why it's used in different parts of the body as well.

38:30The thing is, though, that it only works on three of the eight pathways. So, you have five pathways that you have to upregulate. Tretinoin doesn't really work in any of those other than it has some effect in thickening the total epidermis. but doesn't improve barrier function at all. And back 20 years ago, 30 years ago, 10 years ago, people understood that those agents, the tretinoids and the retinoids are photosensitive, but that seemed to disappear from the literature about a dozen years ago. And I've been surprised at how many young dermatologists were not aware that that was actually an issue.

39:05Now, my background with that, we'd done work with that with Dr. Stoughton at UC San Diego in some work for anti-cancer effect of the retinoids. And the retinoids are powerful. But as I said, when you look at the skin pathways, you've got 13 pathways that need to be modulated and it works on three of them. And then the other problem is, is that how does it work? Well, it increases proliferation. And with doing that, you can speed up the proliferation enough, you'll actually can have higher incidences of various types of abnormalities and pre-cancers and so on occurring. And I was at the meeting in Cannes, France in February of 1985 when Dr.

39:43Kligman presented the first information about anti-aging effect of tretinoin. The speaker before him talked about how the use of the tretinoin increased the incidence of sun-induced precancers. All the publicity went for the anti-wrinkling effect that Dr. Kligman talked about. And so I was a very big retinoid user. Within a couple of years, I was the biggest retinoid user in Oregon. And because I was trying to get rid of all these precancers, particularly in younger people, young adults, I was just stunned at how the frequency was. And that was one reason why we did all the research. I wanted to help reduce the incidence of precancers and skin cancers in young people.

40:20So I was taking melanomas off of six-year-olds, squamous cell carcinomas off 11-year-olds. I mean, things that, you know, you just don't normally see in most of the population. So anyway, it was then we started seeing that early on there would be benefit. but then there would be increased incidence over time. And that was one of the issues that made me think about, we need to look at this differently because we did know that it had an impact adversely on the stratum corneum and the photosensitivity. And so the benefit, it walked a very fine therapeutic line or to true knife edge as far as producing too much activity.

40:57And so I think there's a reason why, well, I know there's a reason why they are telling people now that use them for a certain period of time, six to 12 months, and you need to go to a maintenance dose of one to two times a week and so on. And the reason for that is, is because adverse reactions started occurring and you started seeing increased incidence of other aspects, like increased incidence of sun-induced precancers, increased incidence of skin sensitivity, increased reactions. I mean, the incidence of contact reactions in the last 12 years to cosmetics has increased from 17 % to 55%. Oh my goodness.

41:34Okay. The incidence of sensitive skin is over 50 % in several races and all the races, it's at least 30%. Okay. So that tells you that there's abnormalities occurring. So how much of that is actually related to the skincare regimens and that, which I think it clearly has. And I think the use of high dose vitamin C and high dose vitamin A is a big contributor. Yeah, no, that really, really clarifies a lot for me actually because tretinoin right now, there's just a lot of conversation around retinoids in general. And I know a lot of companies are marketing, for example, retinol. I know Bakuchiol became a thing.

42:12That's been one of my biggest questions is that we look at vitamin A, we look at it in leukemias, we look at it in actual very serious cancers. And yes, we understand that it can repopulate an entire cell population, but do we want to be doing that every single day on our skin for years and years and years? That's right. Interesting about Bakuchiol, there was a Cochrane report just last year showing when they looked at the 15 clinical trials with Bakuchiol, basically there was no benefit. Even though people are saying, oh, it has this activity, the reality is it didn't. There were no randomized controlled trials done.

42:52The trials were very poor quality and the conclusion was, no, a coochial doesn't work. But again, that's an example of somebody discovering something of, hey, what can we do for the marketing story? And I think that's where I primarily diverge from many of the other thought leaders in the area of dermatology. I am first and foremost a physician. I want to make sure products are safe and effective. That's why we were the first ones to do those RCTs against prescription products. And we were also the first ones to start doing the repeat insult patch test safety study on all of our products. And I know it was important because people, I got attacked for raising the bar and for changing how we look at cosmetics and so on.

43:38And a cosmeceutical, the definition is it has impacts on structure and function temporarily like a drug, but it's got the elegance of a cosmetic. But there's not really any federal regulation around that area. It's not like in Japan where you have quasi-drugs that are well-regulated and so on, and like our OTC, FDA-approved monographed ingredients and that sort of thing. No, no, it's really, really fascinating. And I think that's why I want you to speak about the way that you've built Epionce because you haven't strayed from this idea of focusing on what really the skin needs. And I would love for you to speak on carrying that integrity forward as obviously, I mean, you are a physician and the science is always first, but even in the entrepreneurial space, I'd love for you to offer some advice in this industry because I don't understand why, I don't want to sound mean when I say this to anyone listening, but there are a lot of physicians right now that I wonder, where is your brain, you know, when you're making some of these products?

44:37Because they're not meant to do what they're claiming to do. You know, you're putting 18 ingredients into a bottle and claiming that this is going to fix like what we were talking about earlier, hyperpigmentation or wrinkles or whatever it might be. It's just not plausible. That's just not plausible, obviously, in a formula, but also everything you've discussed here, your skin doesn't work like that. You know, there are things like receptor saturation. There are things like too much exposure to certain ingredients and factors. And so I'd love for you to offer this advice on that entrepreneurial scale, you know, of like, how can people still innovate, but not lose sight of what's actually going to move the needle for the skin?

45:11That's a very good question and a dilemma that I think all skin professionals wrestle with to some degree. In my situation, because I was first and foremost a physician, my goal was to prevent, as I mentioned earlier, pre-cancers in young people to prevent the diseases that occur as we mature and the diseases that occur with activation from environmental insults. And also, I wanted to get clear from my dermatitis and stay clear and not have the reactions to the various medications that were being used. So we really had that five foundation and having the investigator's mind because I'd done multiple phase three clinical trials when I was a resident and I had already patented azelaic acid for treatment of rosacea, which became Phenation.

45:58As I mentioned, 22 patents, but it was always looking at understanding the underlying of biochemistry and the molecular level. I used to think that all doctors thought like that. I was so surprised when I found that's not the case. A lot of them don't think like that. And also because of variety of economic issues and so on, they may have a different desire for what they're trying to develop. Our goal was to make products that were safe and effective and worked on the foundational problems. So for example, if we look at eczema patients and treated this as comparison with a megapotent topical cortosteroid clobidazole, used twice a day, all the patients were cleared within three weeks.

46:39Problem was when they stopped the treatment, they all rebounded within four weeks. Using the barrier repair technology, it took seven weeks for them to completely clear, even though they started noticing significant benefit within two days. But there was no recurrence of any lesions for eight and a half months, which tells you we were really working on the foundational problem. Okay. And that's what drives me is producing that long-term benefit. But because our goal was very different and because I came out of the pharmaceutical industry, I needed to start a company and do the research ourselves and then build upon that.

47:16And if we could find things that would result in products, terrific. But we needed to do the understanding research. And as I mentioned, the relationship with Peter Elias and his great team. So we did that nine years of the basic research, and then we needed to prove efficacy and safety. So we did that with clinical studies. In 2003, we took on tretinoin 0.05 % emollient combined with their lactic acid moisturizer. And we were twice as good in rejuvenating the epidermis and the dermis. And we had no irritation. Oh yeah, we got rid of 97 % of the visible precancers as well. Oh, and 38 % of the hyperpigmentation went away, even though we had no depigmentors in our product line.

47:55Wow. Okay. And so when other companies come out and say, oh, well, we've combined a retinoid and hydroxy acid, so this is a big breakthrough. Yeah, actually we showed over 20 years ago that that's not the case, that we were better. But I think the differentiating point was I focused so much on the research early on rather than spending money on marketing. Because, as I said, I thought doctors thought like I did and realized that a lot of them didn't. And so having been a lineman on championship teams in football, I knew the importance of having the team. And so I went out and found a group of people that would buy off on the vision and had skill sets that I lacked.

48:39I'm really good at a few things, but I really suck at a lot of things. So I needed to bring people in that could overcome my deficiencies. And together, we were able to produce what we have as EpiOnts today. There was also a learning process for that, and it took risk. I mean, twice, I second mortgaged my house. I completely exhausted all my retirement funds to finance the original research and all these sorts of things. So I took big risk. And fortunately, my wife of almost 53 years agreed to do that. And so we were able to be a successful company. In other words, from the very beginning, our philosophy was different than others.

49:17And having sat on scientific advisory boards for several cosmetic companies, I had a pretty good idea what kind of products they would not be producing, but what kind of products I needed in my practice to help me be a better doctor, okay, to reach the five goals. And so I had a concept of 14 products. We have completed 13 of those. The 14th is in process now. And so we've been successful in focusing in that particular area. As we grew organically, we were able to decrease cost of individual SKUs, as we were able to increase volume of usage. And we were also able to add more SKUs based on more research, able to do more clinical trials.

49:58We just finished our 37th clinical trial last year. Okay. And more than 15 of those have been RCTs. And so that's what our major focus has been over the time. And I'm very proud of how our marketing team and so on has been doing now. And as we're building the company and spending more money and effort in the marketing arena, but we were the first in so many aspects of it. And as I said, first for safety studies, first for blinded trials against prescription products. And incidentally, we've taken on 13 prescriptions. We've beaten them all in efficacy and safety. Okay. 13 gold standard products.

50:34So we've accomplished a lot. And so I'm very gratified to be able to stand here and say, yes, we have been able to accomplish a lot. I was hoping that this technology and the concepts would spread throughout the entire world, but I realized that there's only a portion of people who absolutely are really driven by optimum skin health. They're willing to pay the price in their lifestyle and so on to make the changes to optimize their health. That's really what we're trying to do. You'll have maximum beauty with optimum skin health. You're going to have the best health span. In other words, the years of quality living before you move into your terminal stages, that's lengthened.

51:14And the Framingham study showed that people who were pleased with the appearance of their skin actually lived longer, had higher survival of heart surgeries, had lower incidence of use of prescription medications than those that did not. So we know there's tremendous health benefits for having healthy skin. And that's what our major driver is, optimize health. And what that means is we have to look past what is the fad products. We don't use fad ingredients because when we did studies looking at them, they weren't that effective. or we couldn't deliver them at the therapeutic concentration, or they weren't stable when we mixed them with other ingredients.

51:51So it's really been really science-focused, and I've just stuck with that. And as long as I'm in control of the company, which I am, we will continue focusing on that. Now, as new technologies come out, because there's so many bright innovators out there, some of them, they're just incredible things. The quorum issue, the microbiome issue, all these are really important. That's cell signaling, the exosomes. But the key, I think, for the whole story with a lot of these signaling systems and including with like growth factors, you know, how are they actually working? Well, they're working by second messengers.

52:27Well, how can you assume that that second messenger is going to have normal structure and function and go to the right receptor if the cell and the structure is damaged? Aging skin is damaged skin. You can't assume it's going to be able to create the right second messengers that are going to consistently produce the right signaling or the right message on the particular cells. So there's a lot of other factors that people overlook because it's not amenable to short marketing bursts, is my opinion on this. And I'm not a marketeer, and I have learned a lot about this whole aspect over the years.

53:02But as you know, and with all your different degrees, you have to be a continual learner. And if you don't have that attitude is that, you know, you can always learn from somebody else. There's always bright people out there coming in. You're going to go backwards. You know, you really need to continue to be a learner. So I do evaluate new technologies are coming out. We do a significant amount of literature searches. And my research assistant actually had been my senior nurse for 32 years. And so she knows how I think that she's seen EpiAus from the very beginning and so on. So we're able to work very well.

53:33And I have a great team here and I'm just very thankful for the group we have and we wouldn't be where we are without the whole team. I love that. And I cannot truly like applaud you enough for sticking to your guns with the science. Like I really admire that. And I think that we can learn so much from your approach and what you've accomplished in this entire space of dermatology, of skin health. And I really hope that, you know, the future of skincare is going to be more of leaning into this direction that you've already established, you know, because I do wonder, you know, I've interviewed a lot of brands on this podcast and some of the technologies, although they sound very interesting and, you know, exciting, the physiologist in me is always like, yeah, you know, this is very cool.

54:14But the mechanism and the data and the proof, it's just never there. And I feel like we're putting that cart before the horse so many times, you know, in this space. So I absolutely agree. And so it's so refreshing to hear you share that there are other people like me that think along those same lines and how important it is. And that's one reason why we do all of our own manufacturing as well. We don't farm anything else because I want to make absolutely sure that we have all the ingredients and the formulations are made properly. So it's an exciting world and I've been incredibly blessed and I've been in the industry long enough.

54:44I've seen concepts come and go and failed for a lot of reasons. And most of it is they could never prove that they actually worked with the finished products. Yeah, I think that's the biggest hurdle. And you know, it's funny because I started this, I mean, I'm just telling you off the books, I started the seal. It's like a validation seal, you know, it's like basically show me your data kind of thing. Like show me the proof of the final product that you've shown, you've proven that it works, you know, and I kid you not the amount of brands that have said, yeah, I'm interested in the seal, but then you ask them for the data and they're just like, no, like I'm, I'm not showing you anything.

55:16It's disheartening because I aligned with what you've explained in this whole podcast, you know, I really aligned with that as a scientist and also a consumer. And it's sad to see that companies don't want to be more transparent about their science, you know, and say like, we put in the time in the right place, you know, in the right research, and we can prove that, you know, at the end of the day, I hope that that shifts at some point, you know, and people start realizing like, yeah, you're selling a product, but you're also selling an adjunct health solution for so many people. Like there are people in rural parts of this country that have no access to dermatologists.

55:49They have no access to proper healthcare. And their only option is over-the-counter products, you know, consumer-based products. And it's like, where is that duty then at the end of the day on the behalf of these brands that you have to serve that consumer? You have to serve that, you know, like in the same way that we learn in healthcare and in medicine, do no harm, that kind of thing. So, yeah. Thank you so much, doc. This has been, I can't tell you how much of a breath of fresh air this conversation has been for me. I can't thank you enough for your time. This is amazing. Well, thank you so much for giving me this opportunity to share.

56:22And it is exciting and it's been a long road, but it's been worth it. The impact and the patients that I have are the people that tell me about how it's changed their lives. I mean, just the other day I had a person said, oh, you're the Dr. Thornfeld that invented this. This product has changed the life of my family and myself. It's incredible, you know, And just to have those kinds of positive results is just so gratifying. I want to ask you one more thing, though. I want to ask you, you mentioned azelaic acid. You patented azelaic acid. Yeah, I did the original research on that. And the reason was that I was using it.

56:57We were making ricin at the time to attach to monoclonal antibodies to treat terminal melanoma with a company called Hybridon. So the first biotech company in San Diego. And so I was extracting that from the castor bean. and it had about a 70 % prolongation of life for a year. But I wondered why wasn't the castor being destroyed because the ricin was such a potent weapon to mass destruction. And it was because it was bound to the azelaic acid. And so I really started looking at the azelaic acid and found that it had some very potent type of effects when I looked at veterinary medicine, cellular biology, all these different disciplines out there, but nobody really put it together for dermatology.

57:35And because it was a lipid, and we had done all this work with Dr. Stoughton and was involved with the development of diprolene and alkalometasone. Those were a couple of those projects I worked on and getting those invented. I had a very good basis in lipid biology already of the skin. And so I found that the azelaic acid not only was very potent for anti-inflammatory, but it was also broad spectrum anti-inflammatory, also broad spectrum antimicrobial was also prevented metaplasia that occurred. And even as a drug delivery agent for 5-FU, we were able to turn down the incidence of contact reactions and improve the killing of actinic keratosis, particularly hypertrophic actinic keratosis using the azelaic acid as a carrier for 5-FU.

58:19So I had a number of patents with azelaic acid, including the original patents for rosacea, seborrheic dermatitis, and actinic keratosis. And so back in 1986. Yeah. So. That's so impressive. Like I'm just so blown away with all of your discoveries. That's amazing. Yeah, I see it everywhere now. Everyone's trying to get behind using it as more and more. And so it's interesting to see the drug come up more in conversation now. But that's profound. Yeah, the key with that more than anything is its formulation system. There's very specific things that you need to do. And that's why we have it in so many of our products, because I know what it does.

58:58And I know that it also transports some of these very difficult architecturally irregular molecules to deliver them to the right strata. Wow. Well, thank you so much. This has been this is amazing. I'd love to have you back. I was wondering. I'd love to come back. Thank you. There's so much more to talk about along. Once again, thank you so much for taking the time. This has been a real pleasure. So this is my first true podcast. So. Oh, you did amazing. This was wonderful. I think this is one of my best podcasts I've recorded this year. So. Yeah. Great. Thank you so much. Thank you so much.