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I will get in touch with them! Thanks.

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Blue skin might protect you from vampires / psychics? 

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Agree with Perry, from best to worst:

1. Reputable suppliers directly found through e.g. ulprospector (MOQs can be high)
2. Reputable repackagers like lotioncrafter or makingcosmetics, ideally with COAs (they buy from suppliers and repackage / rename the raws to sell them in smaller quantities at a 30-70% markup).
3. Amazon (there’s a review system and amazon has good return policies)
4. Ebay (poor return options, no product reviews)

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Very interesting Belassi, I’ve asked JUNGBUNZLAUER what grade they have has the least scent (they supply food grade, personal care grade en pharmaceutical grade).

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Basically I’m making the argument that extracts CAN work, and refuting that they can NEVER work.

C.  Inconsistent supply - you’re never able to buy exactly the same extract twice.
D.  Questionable supply - you have no reliable way to identify the composition of an extract. Is it licorice extract or propylene glycol spiked with brown food coloring?
…
are you suggesting there are no unscrupulous suppliers?

No I am sure you’re right that there are, but you were making too strong negative claims, that you can NEVER buy the same extract twice or that there is NO way of identifying what it contains. A combination of using reputable vendors and per-batch analysis of the extracts will get around the issue of supply consistency. This also holds true for willow bark extract and it still holds that I disputed your claim, given that you know the amount of salicin you’re getting. Extracts can work.

Where is a successful product on the market that is based only on an extract as its functional ingredient?

You can make a “successful product” with nothing than rebranded petrolatum, which wouldn’t prove anything. One example of a good product that uses licorice root extract (+AHA) is acne.org’s moisturizer, and they use enough to turn it pale yellow (if it’s not food coloring .

If you dig a bit you can find studies where extracts or purified components of them  were added to base formulas and tested against the base formula alone (amazing how often they fail to test against the same base! often likely due to manufacturers sponsoring the trials..), which is what I’ll be doing next, then you’ll want to find several such studies and see if they agree. 

Also, if you know salicylic acid is the functional ingredient why wouldn’t you just use that in your formulation instead of an extract that contains a small amount of it? Using the ingredient directly gives you much more control as a formulator.

One major reason is if you don’t want your formula to be an OTC or even Rx drug.

Why use Chamomile essential oil (37% Bisabolol) vs purified Bisabolol? You might want to use Chamomile EO if there are other useful constituents you want to include in your product or if you want the scent profile, OR use pure Bisabolol if the scent profile of Chamomile EO is too strong at the dose you’d need to use. Then there are marketing and price considerations.

Personally I just want whatever works.

Only through proper testing can we discover what is actually effective. Wouldn’t you agree?

I agree that the western method of testing efficacy is the best method we have to date, and that there is a lot of eastern medicine that’s not effective. There are however examples of eastern medicines that were effective, which was subsequently proven by western evidence standards and turned into drugs.

I also don’t understand how double blind studies are “western” standards? It seems to me they are just science. The same kind of science done by people in Japan, Korea, China, Thailand, etc. What am I missing? 

They’re western because we came up with them, now they’re of course used all over the world and traditional eastern medicine is being either verified or debunked by what’s our current best bet standard of truth. I’m not promoting traditional eastern medicine’s standard of evidence.

But there’s no such thing as just science when it comes to testing compounds, I alluded to some of the problems with our standard of evidence (based medicine) in my last post, these will continue to evolve and hopefully reduce the incidence of false positive and negative results (pre-registration of studies is another interesting requirement we could see in the future).

There’s also not such a thing as just medicine, evidence based medicine considers evidence of different strength, it’s not black and white:

• Level I: Evidence obtained from at least one properly designed randomized controlled trial.
• Level II-1: Evidence obtained from well-designed controlled trials without randomization.
• Level II-2: Evidence obtained from well-designed cohort studies or case-control studies, preferably from more than one center or research group.
• Level II-3: Evidence obtained from multiple time series designs with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.
• Level III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

https://en.wikipedia.org/wiki/Evidence-based_medicine

One hypothetical example of why Level III evidence should be considered: Treatments that one doctor found to work for his patients might work because they for example are all from Iceland, whereas RCT’s that found no effect were done on people with a different genotype or some other demographic difference.

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C & D.  Supply - It’s much easier to doctor natural ingredients than you know. People still sell and buy grapefruit seed extract as a preservative, even though it’s been fairly well demonstrated to only work because it is spiked with parabens. You may have more faith in the sincerity of suppliers than I do. I’ve just seen a lot of shenanigans that go on in the cosmetic industry.

Think e.g. Seppic or CLR-Berlin would risk their reputation by selling fake ingredients? I don’t think so, especially with the ease of which you can do analysis now to verify that you’re getting what you paid for.

you could dispute the claim by showing a product that uses only an extract as its main ingredient and the results from that. AFAIK there is no such product. 

Easy to prove you wrong here, look at any of the FDA approved OTC ingredients for various skin issues and then look for extracts that contain them, e.g. willow bark extract containing salicin which is metabolized to salicylic acid in the skin - you just need to make sure you’re using enough to get effects, which would require HPLC analysis of the extract and/or using standardized ones by reputable suppliers.

I would say no “eastern medicine” that hasn’t been proven by a double-blind study works. Similarly, no “western medicine” that hasn’t been proven by a double-blind study works either. There is no such thing as “alternative medicine.”  There are just things that work, and things that don’t.  Which eastern medicine “works” that hasn’t been incorporated into working medicine?

One example, Artemisinin contained in sweet wormwood which was used in eastern medicine for more than 2000 years to treat malaria, in 1969 an extract of the plant was found effective (using a similar cold extraction process recommended 340 BCE), later Arthemisinin was purified and sold as a drug. https://en.wikipedia.org/wiki/Artemisinin (naturally it’s best to have a standardized drug, but that doesn’t mean the herbal extracts didn’t work).

It’s seems arrogant to say that no eastern medicine that hasn’t been verified by our western standards has any effect, have we tested them all? No. Even double blinded placebo controlled trials are flawed and can loose signal in averages (if a treatment only works for people with a certain genetic makeup etc, creating false negatives), or can show statistically significant results with only weak effects with large enough n’s.

You can find more examples in 2011 “Evidence-based Medicine for Traditional Chinese Medicine: Exploring the Evidence from a Western Medicine Perspective”.

In Alzheimer’s treatment some doctors have started prescribing standardized and increased bioavailability versions of Curcumin as adjuvants made by reputable companies such as Now or Jarrows (companies that have been tested by Consumerlabs several times and always sold what they say they do).

I digress

Looks like I have some reading to do, Bisabolol and Dipotassium Glycyrrhizate were already on my list, the big questions are how they compare, whether they can be sourced from reputable vendors and whether they’re likely to have clinical effects at practical/affordable use levels.

Honestly if you wanted to do this right you’d need to assay their effects in the final product in vivo.

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Thanks for the detailed answer! Always healthy with a solid dose of skepticism when it comes to cosmeceuticals, but I think you may be too dismissive so not closing the thread for submissions just yet..

Counterarguments:

A.  Publication bias - no one publishes the studies where they found no effect
Applies to all research and not entirely true, there are still studies published showing no or little effect.

B.  Motivated researchers - most of the studies are published by people who want to find an effect.
Applies to all research, but possibly less true with natural ingredients that can’t easily be patented as there are less financial incentives.

C & D.  Inconsistent/questionable supply - you’re never able to buy exactly the same extract twice.
Non issue with a lot of extracts, will a thyme essential oil not contain thymol? Will NOW foods sell you brown scented food coloring? Very unlikely and hard to fake due to the scent. AFAIK the variability of constituents of essential oils also isn’t high enough to make any performance difference.

With more sensitive and low concentration constituents the extraction method could be critical, and you would have to get HPLC data to verify that your extract contains what you’re after both pre and post manufacture possibly for each batch.

1.  No extract works reliably enough to base a formula on it.
Bold claim that needs to be substantiated. It’s a bit like saying no eastern medicine works because nothing has gone through phase III trials.

2.  No, non-OTC ingredients are not better & they don’t work reliably.
Generally this is true, but not necessarily always. Depends on the degree of reliability, it’s not a black and white issue.

3.  No/yes - These are claims ingredients & they help convince people to buy your otherwise standard product.  But they can introduce unknown allergens and can actually cause problems with your product.
Definitely important to look at sensitization data if including something, yet not all extracts are made equal and some have very good tolerability profiles AFAIK.

(4). The reality is that if there was an extract that was effective, researchers would figure out which ingredient in that extract was responsible for the effect. That ingredient would be isolated and then that’s what would be recommended for use. Lots of the effective drugs we use today came from some plant extract. There is nothing special that the extract provides that a synthesized version of the active ingredient couldn’t.

Definitely, most of our drugs historically came from natural compounds, and researchers are isolating ingredients to see if they are effective and there is some evidence that they are (often fraught with methodological issues unfortunately, so it is indeed hard to draw solid conclusions).

They are also recommended for use and sold (sometimes with hplc data) by reputable suppliers, but there is a huge $ gap from that to getting them approved for treatment of diseases as an OTC or rx drug (we see a similar trend in supplements, companies making improved forms of e.g. curcumin to increase bioavailability or BBB penetration etc). Even getting studies done by third parties is expensive and difficult to do right (btw, only one such study showing any significant effect is all the EU needs for you to sell something as treatment!).

I’m however not set on using extracts vs purified or synthesized constituents of extracts.

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Guess it’s hard/near impossible to say if Montanov 202 would offer much of a performance benefit over Glyceryl Stearate.

Will make the base now with saccharide isomerate instead of sodium pca.

As for non glucoside emulsifiers Potassium Cetyl Phosphate looks interesting, but have 0 experience with it.

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Seems like replacing glyceryl stearate with Montanov 202 as a co-emuslifier could lead to some benefit? (at 5x the cost)

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@jemolian thanks, so we’re already using glyceryl stearate as a co-emulsifer, maybe Montanov L could be a drop in replacement here? But it’s still an alkyl glucoside so It will be as likely to trigger reactions as Montanov 82.

They do specify 82 for sunscreen applications, moisturization wise they L and 82 performs identically

They also claim 3% Aquaxyl nearly doubles this performance

@Cahterine have not tried dimethiconol! Are you saying to not use linoleic acid (in free fatty acid form)?

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Allergies to alkyl glucosides are uncommon, 30 cases in 11842 people or in 0.25% of people, but they are however more common in older women with a history of atopic dermatitis. https://onlinelibrary.wiley.com/doi/abs/10.1111/cod.12154

“Allergy to alkyl glucosides is more common in females than males, likely due to females’ higher use of personal care products.5,9 The median age of those sensitized is 49.6 years. Conditions such as atopic dermatitis (AD) and occupational irritation may increase the risk of ACD to alkyl glucosides by affecting the skin barrier and allowing greater penetration of the allergen(s).5 Furthermore, people with atopy or sensitive skin might self-select those products marketed for sensitive skin, many of which contain alkyl glucosides. ” https://www.the-dermatologist.com/article/update-alkyl-glucosides

What’s the best emulsifier then for such a formula?

Jojoba esters seem to offer around 2x better TEWL reduction performance than Shea Butter, at least if we are to believe floratech. So adding it and increasing the gum percentage could be an idea here.

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2% dimethicone (unknown CPS) showed some benefit, albeit it was not as long lasting as glycerin etc. Maybe using 2% is worth it? After all it doesn’t negatively affect skin feel even at 1000 CPS?

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Thanks! 

One thing the formula is missing is a thickening emollient, originally used 4% jojoba ester 60 but that was on the low side plus it’s a quite expensive ingredient. Any suggestions here? Cetyl alcohol? Some other natural petrolatum alternative? Or simply petrolatum?

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Want to stick with a base I know for now, since development resources are limited. Still o/w with a 10% oil phase (or do you mean just oil?) will not necessarily feel greasy?

What are the best elegant/long lasting moisturizers on the market in your opinion? Any w/o ones?

I’m a bit vary of polymers after I saw some evidence that sodium acrylate polymers seemed to increase TEWL over time (2006 Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial) and there’s very limited data on toxicity http://www.cir-safety.org/sites/default/files/ACTAPY122015rep.pdf

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Good point nga! And a very difficult question to answer, I don’t think you can generalize too much and it probably comes down the the individual emollient and etiology of acne/eczema in the person.

The goal with this moisturizer is to make an elegant and light formula that still gives long lasting moisturiziation, enabled by e.g the lipid/fatty acid combo, perhaps saccharide isomerate etc. 

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Thanks Perry!

We have some data to indicate a performance benefit from the lipids, and there’re several of studies supporting the amounts and ratios used, in some cases, taking one out nullifies the effect. In any case, that’s a separate discussion (i.e. what actives/special features to add and whether they are effective).

Focusing on the moisturizer base, glycerin is also used as a dispersion aid for the gum, but Sodium PCA could be replaced with Saccharide Isomerate if the latter gives a longer lasting effect, something to test that could be noticeable.

One major question is the value of using SqualEne over Capric/caprylic Triglycerides, if using the shark liver type cost would be comparable, trying to look into if squalene - which plausibly could work as an antioxidant unlike squalane, and is depleted in skin subjected to pollutants (opening for anti pollution marketing), is stable enough to work as a replacement.

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Thanks for the tips, the two worst offenders in terms of cost are cholesterol and ceramide 3 here which make up 66% of the total cost(!), don’t think there’re any easy ways to save there besides reducing the amounts used.

There might be marginal savings on the emulsifier and the linoleic acid source (which is in triglyceride form in natural oils, so they’re not equivalent AFAIK, very little free linoleic acid them).

@LincsChemist I don’t see any studies on saccharide isomerate, but seems like it’s a “second generation” humectant, have you seen any studies comparing it with glycerin et al? Any drawbacks with it? 

Here’s the pentavin discussion incl some references https://chemistscorner.com/cosmeticsciencetalk/discussion/5025/saccharide-isomerate

Here’s DSMs formula:

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Tried em all, dimethicone is 3x as good as the second best option.

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Thanks! Seems like rice bran wax could be an alternative to microcrystalline wax also.

Here’s some info https://formulabotanica.com/natural-cosmetic-waxes/

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2018 Imaging the distribution of skin lipids and topically applied compounds in human skin using mass spectrometry

tl;dr Topically applied ceramides do go into the Stratum Corneum. Wondering what the case is for cholesterol..

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@antmagn how much Gosulin IL did you use to reduce whitening?

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Thanks Vnnil. Why not higher cst? 1000 cst seems to work fine.

Bill: 5% Jojoba.

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@ngarayeva001 in that case it would be the emulsifier combined with stearic acid as we didn’t have the issue using stearic acid + ewax.

@crillz you’re right and I realize that “soaping” is the term for what I want to avoid, in another thread from 2014 some alternatives to dimethicone were proposed https://chemistscorner.com/cosmeticsciencetalk/discussion/781/natural-anti-soaping-whitening-effect-ingredients

2% CPS1000 dimethicone does indeed cut soaping in half or so, but Dicaprylyl Ether and Isoamyl Laurate was proposed as natural alternatives. Wondering if DOW 1400 or 1401 could work even better than dimethicone also.

Things to try:
1. Remove stearic acid
2. Try a different gelling agent
3. Add 2% dimethicone CPS1000
4. Add 4% Dicaprylyl Ether or Isoamyl Laurate.

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A contract is a very good idea if one can get a CMO to agree with it. Although isn’t an implicit agreement a bit of a contract too?

We do typically have quotes from other manufactures, still switching can take a lot of time and significant sales losses can occur from going out of stock.

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@gunther I appreciate your concern, but already done with one round of in-vivo SPF testing. It is however very true that it’s expensive to keep doing in-vivio test which AFAIK there is no substitute for with mineral sunscreens (with organics you can get comparable results in vitro).

@Bill_Toge I think the answer might be yes, Kobo claims that they’ve achieved 6.17 SPF pr % mineral (TiO2 + ZnO), so it might be possible to get to 3 with ZnO only. 

Sunscreen actives
TiO2 (40 nm) 3.54% 

ZnO (265 nm) 7.15%
Antioxidant/ Anti-inflammatory
Booster blend ATB 5.00% (Argan Oil, Tocopherol, Bisabolol)

UV absorber/Stabilizer 

Ethylhexyl Methoxycrylene 1.37% (Boosts PFA, might protect from mineral tox)

Butyloctyl salicyalte 4.48% 

Film former
Acrylates copolymer 1.5% 

Index Value SPF 66

Estimated value without boosters SPF 15 - 20 

PFA 21 Estimated PFA without boosters 5 

CW (nm) 380