Coal Tar...............alpha five reductase inhibitor

[michael barry]

This is what you get when you are up at one-thirty in the morning reading obscure hair patents. I outta have my head examined.


Lookie here: http://www.patentstorm.us/patents/56098 ... ption.html



"[LCD functions as an inhibitor of enzyme catalytic activity by suppressing the conversion of testosterone to dihydrotestosterone through its ability to deactivate the co-enzyme NADP which is required by 5a-reductase in the above conversion process.

/i]


LCD stands for "Liquor Carbonis Detergens" or Coal tar.





Here is the whole suggested formula with the patent:

Component Parts of solution
%
______________________________________
Liquor carbonis detergens (coal tar)
8 4.4
Salicylic acid 2 1.1
Spirits of Camphor 30 16.7
Castor Oil (or similar oil)
2 1.1
Isopropyl alcohol 138 76.7
Perfume (Range)
*Adjuvents
total 180 100.0
______________________________________
*such as, Minoxidil, RetinA, CPA (Cyproterone acetate), growth stimulatin
factors (supernatants), sulfates, pyrimidines, hexosaccharic acid, salts
and esters thereof, pyroglutamic acid and esters thereof, and
antiandrogens, which can be factored in as desired






On in the literature, the authors explain what each ingredient supposedly would do against alopecia.

-------"LCD functions as an inhibitor of enzyme catalytic activity by suppressing the conversion of testosterone to dihydrotestosterone through its ability to deactivate the co-enzyme NADP which is required by 5a-reductase in the above conversion process.

Salicylic acid works as a blood flow stimulant and as a keratolytic agent, bactericide and an adjunct in fungal infections which may be present on the scalp and inhibiting the normal functioning of the hair root bulb. Salicylic acid also serves to dissolve skin oils and reduce their viscosity within the sebaceous glands and ducts.

Spirits of Camphor (dissolved crystals) is a mild rubefacient, analgesic, antiseptic and antipruritic with mildly irritating and stimulating properties affecting capillary

Isopropyl Alcohol (Isopropanol) serves as a solvent of surface oils, antiseptic, stimulant of blood flow, and media in which the other ingredients are dissolved.

Oil of Ricine (castor oil) is used to improve the regrowth or epithelialization of skin cells by reducing premature epithelial desiccation and cornification. It also acts as a protective covering to the irritated surface skin cells. "




The "Long Version" of how Coal Tar inhibits DHT formation is given further in the patent here:

"An initial comparative study of published findings on alopecia and review of coal tar applications for dermatological disease treatment revealed no explanation for the activity cited above to i.e., the inhibition of the conversion of testosterone to dihydrotestosterone. However, the study of the co-enzymes required for this reaction, namely the interaction of 5a-reductase and NADP (nicotinamide adenine dinucleotide phosphate) revealed a mechanism of action that would explain lower levels of DHT is patients regularly applying the LCD solution. The conversion of testosterone to DHT is catalyzed by 5a-reductase which serves to donate the extra hydrogen atom carried by DHT. To release this atom, 5a-reductase requires the presence of the co-enzyme NADP.

To clarify this point, it may be helpful to review the role of enzymes in human metabolism. Enzymes are protein molecules of high molar mass which serve to catalyze reactions, making it possible for changes to occur faster and/or with reduced levels of energy. Most enzymes contain a non-protein element called a co-enzyme that must be present if the enzyme is to fulfill its function. In some cases, the co-enzyme is a metal cation such as Zn2+, Cu2+ or Co2+. In others, it is an organic molecule, most often a vitamin (such as the B vitamin niacin). DHT is a ligand. Ligands are molecules which are bonded to the central metal in a complex ion (ligands can also be defined as any molecule with an unshared pair of electrons). DHT requires an extra hydrogen atom to convert from testosterone. If this extra hydrogen atom is not available, the conversion cannot occur. Testosterone uses 5a reductase as its substrate. This substrate is one of the family of dehydrogenases, a class of enzymes which serve to remove two electrons and two hydrogen ions from the substrate. Dehydrogenases are very specific to their substrate. The electron acceptor for some dehydrogenases is NADP+, others Use NAP+. If this acceptor is deactivated by the presence of LCD, as is generally recognized (See U.S. Pat. No. 4,102,0995 to Peter Hebborn, Jul. 25, 1978, entitled Tar Gel Formulation, cited below), then the catalytic function of 5a-reductase is inhibited.

Coal tar is credited with an inhibitory action on the pentose cycle in cellular metabolism, which is particularly active in psoriasis. As a result there is a reduction in the activity of the enzymes G6PD and NADP. This inhibitory action is said to reduce DNA and RNA synthesis, resulting in the inhibition of mitotic activity and protein synthesis. A reduction of mitosis, or cell division, is beneficial to the psoriasis patient because . . . one of the factors in psoriasis is the extreme acceleration of epidermal cell production.

The patent excerpt above concerned itself with tar gel formulation and makes reference to the inhibition of the co-enzyme NADP found in coal far as the mechanism of action for the retardation of excessive skin cell reproduction occurring in psoriasis conditions. LCD, a liquid, diluted form of coal tar gel, is likely to have the same or similar inhibiting action on NADP within the cellular metabolism of the hair follicle cells and sebaceous glands. With the deactivation of NADP, 5a-reductase is disabled as the catalyst for T/DHT conversion. The diagram below details the metabolic pathway in human skin of testosterone to dihydrotestosterone.1 ##STR1##

1 The importance of the role of dehydrogenase activity within the sebaceous glands of scalp tissue exhibiting androgenic alopecia is documented by Marty E. Sawaya, et. al., in her published article, "-- 5-3?-Hydroxysteroid Dehydrogenase Activity in Sebaceous Glands of Scalp in Male-Pattern Baldness" (The Society for Investigative Dermatology, December 1987). Their work suggests that bald areas of the scalp have a greater propensity for converting testosterone into DHT through the heightened activity of another dehydrogenase, -- 5-3?-Hydroxysteroid"






Me again...........................I think I now know why the coal tar shampoo group in the finasteride study has such an awkwardly good response now.

 

[vq0]

wouldn't inhibiting NADP be a bad thing?

 

[Bryan]

I'll add here just as a footnote that Sawaya once said in reference to the use of topical zinc, that it _may_ reduce DHT, not so much by directly inhibiting 5a-reductase, but by reducing the amount of the necessary co-factor NADPH.

 

[michael barry]

The Sawaya info is interesting. The authors of this patent try to explain why NADP might be somewhat integral to alpha five's ability to transform testosterone to DHT.


(NOTE: I have no idea whether this REALLY works or not, its just a patent somebody took the time to file-----so Im pretty sure they think it works, and we have that peculiar coal tar shampoo data from that finasteride trial to 'sort of' commend their assertionss).

FURTHERMORE----I tried a coal tar shampoo a couple of years or so ago. Man, the smell is tough. It smells.................well, its hard to describe, but it ain't cosmetic thats for sure. If you could imagine "medicinal + motor oil" that would be about it.



Here is the author's verbiage on NADP embedded in some explanatory language about how alpha five reductase makes DHT, why DHT is so negative to the follicle as compared to DHT, and how inhibiting NADP might 'interfere' with DHT being produced:


"The isolation of a causative factor in the hormonal imbalance which occurs in the balding scalp has led this investigator to pursue the theory that the conversion of the circulating androgen testosterone (T) and dehydroepiandrosterone (DHA), which is secreted by the adrenal cortex, to dihydrotestosterone (DHT) is the primary causative factor in destructive protein expression. Testosterone does not have a high affinity (or attraction) to the binding sites of cells in the sebaceous glands or dermal papilla regions. However, once it is converted to DHT this proclivity to attach or bind rises exponentially (20 to 50 times). In alopecia patients DHT signals the DNA to express, through RNA transcription, a hair protein (shaft) that is thinner, weaker and less capable of sustaining the anagen phase. With age and the repetition of this process, the hair shaft continues to weaken until it finally can no longer sustain pigment, visible growth or significant mass.

It is this investigator's finding that a specific co-enzyme present in LCD serves to block the conversion of DHA and testosterone to DHT.

The formulation of the topical solution referenced above was developed to facilitate the delivery of LCD to the cell membranes of the sebaceous glands adjacent to the hair shaft and to the dermal papilla and contiguous cellular areas. In vivo studies demonstrated that hair loss was significantly retarded with regular application of a LCD formulation.

An initial comparative study of published findings on alopecia and review of coal tar applications for dermatological disease treatment revealed no explanation for the activity cited above to i.e., the inhibition of the conversion of testosterone to dihydrotestosterone. However, the study of the co-enzymes required for this reaction, namely the interaction of 5a-reductase and NADP (nicotinamide adenine dinucleotide phosphate) revealed a mechanism of action that would explain lower levels of DHT is patients regularly applying the LCD solution. The conversion of testosterone to DHT is catalyzed by 5a-reductase which serves to donate the extra hydrogen atom carried by DHT. To release this atom, 5a-reductase requires the presence of the co-enzyme NADP.

To clarify this point, it may be helpful to review the role of enzymes in human metabolism. Enzymes are protein molecules of high molar mass which serve to catalyze reactions, making it possible for changes to occur faster and/or with reduced levels of energy. Most enzymes contain a non-protein element called a co-enzyme that must be present if the enzyme is to fulfill its function. In some cases, the co-enzyme is a metal cation such as Zn2+, Cu2+ or Co2+. In others, it is an organic molecule, most often a vitamin (such as the B vitamin niacin). DHT is a ligand. Ligands are molecules which are bonded to the central metal in a complex ion (ligands can also be defined as any molecule with an unshared pair of electrons). DHT requires an extra hydrogen atom to convert from testosterone. If this extra hydrogen atom is not available, the conversion cannot occur. Testosterone uses 5a reductase as its substrate. This substrate is one of the family of dehydrogenases, a class of enzymes which serve to remove two electrons and two hydrogen ions from the substrate. Dehydrogenases are very specific to their substrate. The electron acceptor for some dehydrogenases is NADP+, others Use NAP+. If this acceptor is deactivated by the presence of LCD, as is generally recognized (See U.S. Pat. No. 4,102,0995 to Peter Hebborn, Jul. 25, 1978, entitled Tar Gel Formulation, cited below), then the catalytic function of 5a-reductase is inhibited."





AGAIN...............................I (Michael Barry) don't know if these guys are right, but they think that they are. The good news is that coal tar shampoos (I imagine one would have to shampoo and leave it in for a minute or so) might be of some extra benefit to our finasteride and other treatments. They do help for certain if you have psoriasis or dandruff as that is well established if you can deal with the smell. It might call for a extra spray of good old' Halston ZX-14 Panty-remover cologne out of the half-gallon bottle to mask that smell though......

 

[blaze]

Nizoral probably is still the best shampoo for Androgenetic Alopecia. I use it everday, the 1% version that is.

 

[Sahar]

http://www.hairlosstalk.com/interact/viewtopic.php?f=11&t=32940

:whistle:

 

[wookster]

Crudoleum :mrgreen:

http://hairloss.about.com/od/hairlosscu ... de_Oil.htm

If someone told you that pure, unrefined Pennsylvania crude oil could restore your hair, would you try it?

[...]

The crude oil concept has since spawned an entire line of Crudoleum® hair products, including a hair rinse, hair conditioner and hair cream.

Literature on Cayce’s original Crudoleum® Hair Treatment says that it’s “no miracle cure†but should be used for several months to fully stimulate growth. Although the balding man I spoke with wasn’t exactly living proof of Crudoleum’s effectiveness, he did point out a study of 45 Crudoleum® users conducted in 1972:

The Stats
*4% reported complete hair restoration, 7% reported considerable hair restoration, 18% reported considerable hair restoration, 18% reported moderate restoration, while 42% reported little restoration and 29% none.

Apparently these numbers are enough to convince the loyal followers of Edgar Cayce. Let’s just hope that none of them smokes.

 

[CCS]

I'll add here just as a footnote that Sawaya once said in reference to the use of topical zinc, that it _may_ reduce DHT, not so much by directly inhibiting 5a-reductase, but by reducing the amount of the necessary co-factor NADPH.

"Forty-four ketoconazole users and forty-three zinc pyrithione users completed the 6 month study period. Analysis of the different parameters shows that the hair diameter gradually increases with chronic ketoconazole use (+8.46%) over a 6 month period, whereas the diameter shows a trend to decrease with zinc pyrithione use over the same period (-2.28%). The sebum excretion rate is reduced with ketoconazole (-6.54%) while it increases with zinc pyrithione (+8.2%) over the same period of time. The number of hair shed over a 24-hour period is reduced by 16.46% with ketoconazole and 6.02% with zinc pyrithione after 6 months. Finally, the percentage hairs in anagen phase increased by 6.4% and 8.4% respectively during the study time. Except for the percentage of hairs in anagen, which showed no difference between the two groups, all other parameters were significantly different in favor of the ketoconazole shampoo."

- http://www.hairlosshelp.com/html/nizoral1study.cfm

 

[blaze]

Speaking of Head And Shoulders,

You can get one that contains menthol now. Menthol comes from peppermint I think. From all reports peppermint is anti-androgenic and should be good for Androgenetic Alopecia.

 

[michael barry]

Blaze,

Menthol can be synthetic or derived from peppermint oil. There is the rub, which is it? The real stuff might be good, but the synthetic may or may not be. Thats why I worry about "menthol". I hope its "derived" of course.

 

[michael barry]

Wook,

I dont think coal tar is from crude oil:


Coal tar
From Wikipedia, the free encyclopedia
• Learn more about using Wikipedia for research •Jump to: navigation, search
Coal tar is a brown or black liquid of high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal is carbonized to make coke or gasified to make coal gas. Coal tars are complex and variable mixtures of phenols, polycyclic aromatic hydrocarbons (PAHs), and heterocyclic compounds. [1]

Contents [hide]
1 Applications
2 Safety
3 See also
4 References



[edit] Applications
Being flammable, coal tar is sometimes used for heating or to fire boilers. Like most heavy oils, it must be heated before it will flow easily.

It can be used in medicated shampoo, soap and ointment, as a treatment for dandruff and psoriasis, as well as being used to kill and repel head lice. When used as a medication in the U.S., coal tar preparations are considered an OTC (over-the-counter drug) pharmaceutical and are subject to regulation by the United States Food and Drug Administration. Name brands include Balnetar, Psoriasin, and Tegrin.


[edit] Safety
According to the International Agency for Research on Cancer, preparations that include more than 5 percent of crude coal tar are Group 1 carcinogen.

Despite this, the National Psoriasis Foundation claims coal tar is a valuable, safe and inexpensive treatment option for millions of people with psoriasis and other scalp conditions, [2] the FDA agrees with this and states that coal tar concentrations between 0.5% and 5% are safe and effective for psoriasis and that no scientific evidence suggests that the coal tar in the concentrations seen in non-prescription treatments is carcinogenic. The NPF states that coal tar contains approximately 10,000 different chemicals, of only about 50% have been identified [3], and the composition of coal tar varies with its origin and type of coal (eg: lignite, bituminous or anthracite) used to make it, so much further research remains to be done on coal tar and its derivatives.



Funny, I was thinking for some reason that it was from burning pine wood and it was part of the black chalky gunk that was left over myself.

 

[liquidfirex]

So just buy some T-Gel? I always liked that shampoo!

 

[CCS]

how powerful of an 5ar inhibitor is coal tar? I'd rather just add some licorice extract to my shampoos.

 

[CCS]

Speaking of Head And Shoulders,

You can get one that contains menthol now. Menthol comes from peppermint I think. From all reports peppermint is anti-androgenic and should be good for Androgenetic Alopecia.

Head & Shoulders Dandruff Shampoo, Refresh
23.7 fl oz (700 ml) $8
Refresh A Cooling Sensation For Normal Hair
Pyrithione Zinc Dandruff Shampoo
* Starts working in 1 wash
* Proven dandruff protection
* H&S HydraZinc formula helps eliminate flakes and relieves scalp dryness, itch, and irritation.
* A refreshing sensation & clean, manageable hair
* Contains natural mint for a cool refreshing sensation and leaves hair clean and manageable
* Gentle and pH balanced for everyday use - even on permed or color-treated hair.


It is cheap enough I might use it as a pre-wash. I don't have problems with lathering though, so I don't need pre-washes. I might get driness from too much shampooing.




Active Ingredients: Pyrithione Zinc (1%) (Anti-Dandruff)

Inactive Ingredients: Water, Sodium Laureth Sulfate, Sodium Lauryl Sulfate, Cocamide MEA, Zinc Carbonate, Glycol Distearate, Fragrance, Dimethicone, Cetyl Alcohol, Guar Hydroxypropyltrimonium Chloride, Menthol, Magnesium Sulfate, Sodium Benzoate, Magnesium Carbonate Hydroxide, Ammonium Laureth Sulfate, Benzyl Alcohol, Sodium Chloride, Methylchloroisothiazolinone, Methylisothiazolinone, Sodium Xylene Sulfonate, Blue 1, Red 4

Why don't you guys just put a few drops of peppermint oil into your other shampoos?

 

[CCS]

I still say zinc is not that strong stopping DHT production, since it did not stop the 1% zinc group from losing hair.

"Forty-four ketoconazole users and forty-three zinc pyrithione users completed the 6 month study period. Analysis of the different parameters shows that the hair diameter gradually increases with chronic ketoconazole use (+8.46%) over a 6 month period, whereas the diameter shows a trend to decrease with zinc pyrithione use over the same period (-2.28%). The sebum excretion rate is reduced with ketoconazole (-6.54%) while it increases with zinc pyrithione (+8.2%) over the same period of time. The number of hair shed over a 24-hour period is reduced by 16.46% with ketoconazole and 6.02% with zinc pyrithione after 6 months. Finally, the percentage hairs in anagen phase increased by 6.4% and 8.4% respectively during the study time. Except for the percentage of hairs in anagen, which showed no difference between the two groups, all other parameters were significantly different in favor of the ketoconazole shampoo."

- http://www.hairlosshelp.com/html/nizoral1study.cfm

I wish there was a placebo group. Are they refering to baseline here?

 

[michael barry]

The licorice oil in shampoo might be a good idea since the smell is going to be notieceable.

I suppose a peppermint oil/purified water mix could be a good spray later.


Like the other poster said, and linked with the Science Direct abstract,,,The evidence really does look good that we have found something that can truly be anti-androgenically useful.

 

[CCS]

Like the other poster said, and linked with the Science Direct abstract,,,The evidence really does look good that we have found something that can truly be anti-androgenically useful.

the licorice or the zinc?

 

[CCS]

1 The importance of the role of dehydrogenase activity within the sebaceous glands of scalp tissue exhibiting androgenic alopecia is documented by Marty E. Sawaya, et. al., in her published article, "-- 5-3?-Hydroxysteroid Dehydrogenase Activity in Sebaceous Glands of Scalp in Male-Pattern Baldness" (The Society for Investigative Dermatology, December 1987). Their work suggests that bald areas of the scalp have a greater propensity for converting testosterone into DHT through the heightened activity of another dehydrogenase, -- 5-3?-Hydroxysteroid".

I'm pretty sure 5-3?-Hydroxysteroid Dehydrogenase it the enzyme that BREAKS DOWN DHT. Makes me question those researchers.

And just how effective is T-Gel at inhibiting NADPH+? How fast is that stuff regenerated? If we don't have seb problems, will we slow the growth of good cells? Is the NADPH+ needed for other enzymes? Coal tar and zink are both supposed to inhibit it, but the zinc shampoo study showed an increase in sebum, and no reduction in hair loss.

 

[CCS]

http://books.google.com/books?id=9Ob_nj ... E89J4Wg_MA

it says here that coal tar can cause acne. not a good sign.

 

[CCS]

would someone post a link to the study with the coal tar shampoo? thanks.