vitalys
Forum Replies Created
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They protect Stratum Corneum from TEWL - the major factor that defines the normal function of the entire skin and its normal physiology.
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Lively skin cells uses so called cellular respiration via the Citric Acid Cycle (or Krebs cycle). This process completely depends on the blood supply and microcirculation in the dermis, since the oxygen is brought from the blood vessels, not from the air. The better microcirculation defines the better skin condition and function. As @Pharma said, only gas exchange takes place in a contact with the air, but it can not be called “breathing”.
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@zetein Yes, but they compared “mildness”. I don’t think pH7 is something awfully dramatic for the skin unless the skin is healthy. Anyway, the buffering system recovers physiological pH quickly. However, the continuous use of surfactants with higher pH can affect skin.
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@Abdullah it’s from “Chemistry of human epidermis” by Wilkerson
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@ariepfadli Perfect explanation!
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@ccchem You are very welcome
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This old diagram explains the correlation between pH and electric charge.
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@Abdullah I doubt the formulations at pH7 could be milder in terms of “dryness” especially in long term perspective. The neutral and alkaline pH ( for the SC) inhibits important enzymes, including those that regulates lamellar bodies, which produce intercellular lipids. At the same time pH 7 and higher hydrates (not moisturizes) the Stratum Corneum for a short period of time. After that water evaporates quickly. Hyperhydration leads to disruption in corneocytes packing. I guess, authors considered short period of time of hyperhydration to be “milder”. Only buffering system of the skin helps to recover the normal (acidic) pH after use.
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I wonder what do authors of the study as well as the marketing leaflet consider to be “milder”?
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@ccchem I would have added to the list you posted the following aspects:
- Molecular weight of an active
- Hydrophilicity/ Lipophilicity of an active substance
- Condition of the Stratum Corneum and its barrier system
- Understanding what an active is going to do when it reaches a particular layer in the SC/the mode of action/biochemical transformation or utilization
All these factors along with those that you have mentioned above will have an impact on penetration and the delivery.
I can not tell any rule of thumb, because the system of the delivery will highly depend on a particular substance that you want to include in your formula.
For instance, keratolytic formulations with Urea are going to be more efficient in the presence of acids and polyols. -
@Graillotion It all depends on the final formulation and its efficacy you wish to achieve. The question is - whether is it going to be a clinical/OTC/prescribed formulation or just a regular moisturizer? I have not worked with mixtures, so it is hard to answer your question. I worked with pure ingredients, which helped to control the necessary ratio. I assume that the mixture you have mentioned is created for the regular moisturizer and the officially recommended percentage of this combo won’t be enough if you want to get something effective. It is not a secret that ceramides, cholesterol, etc are used as “claim” ingredients and they are used in neglectable amounts due to their price. In this case, the resulting formulation would work as a regular standard product. If you want to get something that could work for the skin barriers, you need 3 different pure ingredients. The starting point is 1% of ceramides based on pure substance.
I don’t think it requires microemulsion for extra performance. As I said - the best efficacy would be achieved with w/o emulsions based on polyglycerol emulsifiers or o/w emulsion with lamellar structure ( a combo of high and low emulsifiers).
One of the gold standards (as a product with clinical efficacy) is EpiCeram while CeraVe represents just another quality moisturizer with relatively standard properties, which can be achieved with many other regular ingredients. -
@Sincityfire Yes, it is a part of the ceramide mixture.
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@Perry Yes, he is probably the best in the area of polymer chemistry and coatings for cosmetic applications. I was happy to work with him for one of his books and articles.
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@Graillotion The ceramides physiologically can only be present at the the Stratum Corneum and they are not found at the levels of lively cells - granular or spinous layers. So they have nothing to do any deeper, as @Pattsi mentioned. Their main property is creating the lipid bilayers between keratinocytes to repair the impaired or continuously impaired barrier function of the skin, and they perform this function only when combined with other components of the lipid bilayers - fatty acids and cholesterol in equimolar ratio. This “rule” has been confirmed in many studies. Moreover, as a Dr. Elias et all wrote in his study - ” if the ceramide is
provided without the addition of the other 2 key physiologic lipids at an appropriate ratio, i.e., with cholesterol
and ≥1 fatty acids, barrier function deteriorates rather
than improves”. I have to admit from my experience it is true. Any other ratios don’t work. The measurable data such as TEWL confirm that too. A ceramide or a mixture of them when they are incorporated in the formula alone would work with the same efficacy as with let’s say… shea butter.
However, I can state that some emulsions work better in delivery of ceramides. Polyglycerol emulsifiers w/o are the best when formulating with ceramides in terms of efficiency. -
@chemicalmatt Of course, petrolatum, mineral oils or dimethicone can not be integrated. There have been few studies published and discussed recently. All of them are discussing the role of some ingredients in terms of altering the skin barriers, including lipid bilayers in SC during long term use, which in turn may lead to food allergies, etc. In one study they show that Olive, Sunflower and other natural oils may cause the symptoms of irritated skin and Atopic Dermatitis. Another article states that “…In 13 of the 17 emollients, at least 1 hapten was identified. The haptens found in the preparations were as follows: lanolin, isopropyl myristate, phenoxyethanol, benzyl alcohol, sorbitan oleate, sorbitan sesquioleate, tocopheryl acetate, tocopherol, sorbic acid, propylene glycol, panthenol, ethylhexyl glycerin, cetearyl alcohol, cetyl alcohol, and stearyl alcohol…”
Another work that shows that trilipid cream (ceramides, fatty acids and cholesterol) has more moisturizing potential than the regular mineral oil/petrolatum based moisturizers, but the article seems to be biased, since some authors declare a conflict of interests.
Here are some links to read more about the data and results:
Potentially harmful substances in moisturizers - Journal of Allergy and Clinical Immunology (jacionline.org) -
Water evaporation from the skin’s surface (which is TEWL - TransEpidermal Water Loss) is permanent, never ending process. If a moisturizer has occlusive ingredients in the formula, they prevent TEWL resulting in skin hydration. If additionally, the moisturizer has such ingredients as Urea, Lactic acid and its salts, polyols, etc, they will help retain water in epidermis.
Thus, the complete evaporation of “the surface water” is nonsense. -
@lovermanco I doubt HEMA would be sufficient as one and only component in your system. Regularly the products like this should contain a blend of components. I am pretty sure you will find answers if you go here:
Schoon Scientific and Regulatory Consulting Services
And if you ask Doug Schoon in person. He is one of the best in the nail industry/ formulations for artificial nails. -
@zetein Nice studies! The main points had been hypothesized many years ago before these studies revealed and showed scientifically that many moisturizers can be harmful to the human skin. Indeed, some ingredients or combinations are able to disrupt the structure of the Stratum Corneum and lead to unwanted issues, especially when they come into contacts with prone to sensitization skin. But let’s don’t forget about 3 major things - epidermal/dermal homeostasis, dosage and time - this system of homeostasis (including buffering system) works perfectly well to maintain the balance and protective properties of healthy skin.
Most likely, your own ceramides ( along with another important constituents of the lipid layers) won’t be solubilized - the lipid ingredients of the product will be incorporated into the lipid layers to some extend. However, frequent use of some mixtures may change the structure of those layers resulting in disrupting of epidermal barriers, which in turn will cause the inflammatory events. That is why the use of penetration enhancers should be so conscious since most of them just disrupt the barriers ( including the lipid barriers) in order to increase the permeability of skin. -
@em88 I don’t see any incompatibilities with Urea and SA. Formulating emulsions with them could become a pain but nice pleasant emulsions are possible to create, especially with low Urea concentrations ( up to 10-15%).
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Another marketing gimmick
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@Perry Re: “The long term use of the preparations with high Glycerin content leads to even more severe symptoms of xerosis and related inflammation, especially if Glycerin is the only humectant in the formulation.” - We all know Glycerol is a well studied substance, however, there are many effects of it deserve additional studies and many of the effects are still unknown. I can only share the results we (a groups of cosmetic chemists and dermatologists) we got after commercial studies for a company I used to work for. The company decided to launch the product for strictly professional use by dermatologists, podiatrists, etc. The formulation should contain 20-50% of Glycerin in a relatively simple formulation. Unfortunately, the results have remained unpublished because the company decided to keep it for its own records and use. The purpose of the study was to compare the regular and high Glycerin content to select the right formulation for the product as well as to use the results for marketing. The results were confirmed with corneometry, assessment of TEWL and clinical evaluation of the skin condition. We came to the following conclusions:
Formulations with high Glycerin content are highly efficient to achieve fast, immediate moisturizing effect for short term use. When it was used for a long period of time (2-3 months considering that the skin cells turnout is approx. 30 days), the sudden cessation in treatment caused the worsening of xerosis in 3-7 days. In contrast, the formulations with 7-12% of Glycerin didn’t show symptoms of the xerosis relapse. The addition of 7-10% of Urea (10% most preferable) was efficient in terms of symptoms relief. Addition of sugar alcohols (sorbitol and/or xylitol) was also highly efficient. We didn’t study the mechanisms that stood behind the effects, but of course we just could hypothesize. We ended with the final formulation with 10% of Glycerin, Urea, Sorbitol, Lactic acid, TMG Betaine in o/w carrier. Why 10% ? Because our results correlated with one study where “Four days of twice daily 10% glycerol applications completely reversed the hydration abnorm-alities in asebia J1 SC, and significantly, but incompletely, reversed the abnormality in asebia 2 J animals. Lower concentrations (i.e., from 0.1% to 5% glycerol) significantly increased SC hydration in asebia 2 J animals, but only concentrations above 1% exceeded the impact of the aqueous vehicle alone. In contrast, glycerol concentrations above 10% did not increase SC hydration further…” Again, unfortunately, the current studies don’t answer many questions regarding the Glycerin and its activity in skin.
Glycerol Regulates Stratum Corneum Hydration in Sebaceous Gland Deficient (Asebia) Mice - Journal of Investigative Dermatology (jidonline.org)
Re: “Water
Petrolatum
Glycerin
Mineral Oil”
I won’t dispute this notion is mistaken, since this basic formulation sounds axiomatic to me. I can say the Mineral oil is still the best unparalleled occlusive and emollient (to me). Glycerin is a dose dependent active and can be used even in high concentrations for rinse off formulations, for instance. Although, it ensures the skin hydration only due to occlusive effect effect of Petrolatum/Mineral Oil and Glycerin as only humectant. I assume it is still insufficient in terms of xerosis, the modern standpoint of knowledge about SC and long term use without additional components that I mentioned above. Those components may turn this basic formulation to a better solution because they impact the prime causes of the condition. In other words, the Mineral oil and Glycerin will only solve the symptoms where we can correct the possible source of the problem, e.g. impaired barrier function. -
I completely agree with Tobias that Urea is insoluble in any oil/lipid media.
@Nouranm However, you may make a mixture/paste, which is known in many pharmacopeias and among dermatologists. It includes micronized Urea and fatty base.
Another approach can be efficient - the Glycerin/Oil (waterless emulsion) or water/oil HIPE emulsion. It will look as a nice occlusive ointment. You may also find useful including Lactic acid along with some antimicrobial ingredients in this formulation since the chronic cracks are result of untreated infectious inflammation.
o/w emulsions with the same actives would be less effective. -
@Abdullah
@Graillotion Yes, all that true, but there is neither discrepancy nor conflict. The article you have posted has been based of multiple studies (both double-blind and “commercial”). Most of them show the results of the relatively short term use with different % of Glycerol. The thing is that the highly effective moisturizers actually become a lifelong remedy for people with clinical signs of xerosis or chronic skin dryness. The long term use of the preparations with high Glycerin content leads to even more severe symptoms of xerosis and related inflammation, especially if Glycerin is the only humectant in the formulation. Hypothetically it can be explained by forming that “reservoir” or a depo of Glycerol, which may work as undiluted compound with time, continuous altering of the vital structures in SC and osmotic stress at the moment when the treatment stops. Practically, according to my experience during several trials of highly concentrated Glycerin formulations, majority of people run into severer xerosis than they had before the long term treatment. I tend to call this literally “withdrawal syndrome” when one suddenly stops the cure. That was the reason why we reduced the Glycerol presence in the formulation at least in half.
As I said above, the most effective and safe moisturizer should contain more than one humectant and one occlusive component, and the mixture of actives should cover all aspects of the normal skin water content from aquaporins to NMF and the structure of the lipids. Inclusion of NMF components (Urea, lactates, ammonium salts), lipids (ceramides, sterols/cholesterol, some of fatty acids, squalene, etc) all they will ensure efficient product for xerotic skin conditions in a long term perspective. -
@Abdullah I assume 20% is too much for the moisturizing product. This high glycerin content will have opposite effect and the skin will become even drier.