Topical NO2 as a hairloss/impotence treatment: US Patent

[bornthisway]

Topical and oral delivery of arginine to cause beneficial effects

Abstract
The use of orally administered L-arginine in conjunction with a topical preparation for producing enhanced blood flow in tissue thus causing beneficial effects such as warming cold tissue of the hands and feet, promoting hair growth on bald scalp tissue, promoting healing of superficial Ilcers such as leg ulcers in persons with diabetes, and overcoming male erectile failure (impotence) is disclosed. Specifically, use of orally administered L-arginine in conjunction with this is topical preparation provides local delivery of the amino acid L-arginine, an important biological precursor to the main substance which is responsible for relaxation of blood vessels permitting enhancement of blood flow. In the preferred embodiments, the L-arginine is provided so that it can be topically applied to the cold tissue. The preparation also contains an agent which aids in the transfer of L-arginine into the tissue. In the preferred embodiments this agent overcomes the resistance to transfer caused by the high charge density of L-arginine. In the preferred embodiments this means is high ionic strength created by addition of sodium chloride. This preparation, when topically applied to cold tissue, warming begins within 10 to 45 minutes and is sustained for periods as long as 2 to 18 hours. Further this preparation when applied nightly to bald scalp tissue-for a period of time causes substantial growth of hair on the bald scalp, causes the healing of superficial ulcers such as leg ulcers and overcomes impotence.

Inventors: Fossel; Eric T. (South Hero, VT)
Assignee: New England Property Holdings, LLC (Burlington, VT)
Appl. No.: 734096
Filed: December 11, 2000

Current U.S. Class: 514/565; 424/401; 424/439; 424/450
Intern'l Class: A61K 031/195; A61K 006/00; A61K 047/00; A61K 009/127
Field of Search: 514/565 424/401,450,439

References Cited [Referenced By]

U.S. Patent Documents
5595753 Jan., 1997 Hechtman 424/436.
5629002 May., 1997 Weuffen et al. 424/401.
5925372 Jul., 1999 Berner et al. 424/448.

Other References
Cooper et al., "Transdermal Delivery of Drugs", vol. II, editors Kydonieus and Berner, CRC Press, Inc., Boca Raton, FL, 1987, pp. 57-52. (Library of Congress Card No. 86-2585).

Primary Examiner: Criares; Theodore J.
Attorney, Agent or Firm: Lorusso & Loud

Parent Case Text

CROSS REFERENCE TO RELATED APPLICATION

This is a Divisional application of U.S. Ser. No. 08/936,189, filed Sep. 17, 1997, now U.S. Pat. No. 6,207,713 the contents of which are incorporated herein by reference.

Claims

What is claimed is:

1. A method of promoting hair growth by delivering a nitric oxide releasing substance selected from a member of the group consisting of L-arginine, L-arginine salts and L-arginine derivatives comprising the step of orally administering to the body a delivery vehicle for the substance, said delivery vehicle containing an effective amount of the substance and a concentration of ionic salt sufficient to create a hostile biophysical environment which causes the substance to migrate from said delivery vehicle to the surrounding tissue where it is absorbed.

2. The method of claim 1 wherein the vehicle is selected from a member of the group consisting of capsules, tablets, and liquids containing the substance.

3. The method of claim 1 comprising the further step of topically applying a delivery vehicle containing an effective amount of the substance and a concentration of ionic salt sufficient to create a hostile biophysical environment which causes the substance to migrate from the vehicle to the selected area of skin where hair growth is desired.

4. The method of claim 3 wherein the delivery vehicle that is topically applied is selected from the group consisting of topical creams, topical liquids, topical lotions and topical ointments.

5. The method of claim 3 wherein the delivery vehicle that is topically applied is hydrophobic.

6. The method of claim 3 wherein a transdermal patch containing the delivery vehicle that is topically applied is applied to the selected area of the skin.

7. The method of claim 3 wherein the delivery vehicle that is orally administered further comprises L-arginine from 0.5-30 g/day and the delivery vehicle that is topically administered further comprises water from 20-80%, mineral oil from 3-18%, glyceryl stearate from 0.5-12%, squalene from 0.2-12%, cetyl alcohol from 0.1-11%, propylene glycol stearate from 0.1-11%, wheat germ oil from 0.1-6%, glyceryl stereate from 0.1-6%, isopropyl myristate from 0.1-6%, stearyl stearate from 0.1-6%, polysorbate from 60 0.1-5%, propylene glycol from 0.05-5%, tocopherol acetate from 0.05-5%, collagen from 0.05-5%, sorbitan stearate from 0.05-5%, vitamin A&D from 0.02-4%, triethanolamine from 0.01-4%, methylparaben from 0.01-4%, aloe vera extract from 0.01-4%, imidazolidinyl urea from 0.01-4%, propylparaben from 0.01-4%, bha from 0.01-4%, L-arginine hydrocholide from 0.25-25%, sodium chloride from 0.25-25%, and magnesium chloride from 0.25-25%.

8. The method of claim 7 wherein the delivery vehicle that is topically applied further includes choline chloride from 0.25-25%.

9. The method of claim 7 wherein the delivery vehicle that is topically applied further comprises L-arginine glutamate (0.25-25%).

10. A method of promoting hair growth by delivering a nitric oxide releasing substance selected from a member of the group consisting of L-arginine, L-arginine salts and L-arginine derivatives comprising the step of orally administering to the body a delivery vehicle for the substance, said delivery vehicle containing an effective amount of the substance and a concentration of ionic salt sufficient to create a hostile biophysical environment which causes the substance to migrate from said delivery vehicle to the surrounding tissue where it is absorbed, in conjunction with the step of topically applying to a selected area of skin a topical delivery vehicle containing an effective amount of the substance within a liposome, so that the liposome containing the substance migrates from the delivery vehicle into the skin where the substance is absorbed by tissue.

Description

BACKGROUND

1. Field of the Invention

This invention relates to the use of L-arginine orally alone or in conjunction with topical application of a cream, gel, or other vehicle which contains substances such as L-arginine which delivers these substances into tissue for the purpose of producing beneficial effects such as warming of cold or cool tissues, growth of hair on the scalp, healing of leg ulcers secondary to diabetes or confinement to bed, relief of impotence, as well as beneficial effects through restoration of natural mechanisms based on improvement of local blood supply.

2. Prior Art

Approaches to improving local blood flow have been many and consist of both systemic and topical approaches. Many beneficial effects could be obtained should improvement in local blood flow be achieved since impairment of local blood flow causes a variety of negative consequences. Among these are cold hands and feet, baldness, leg ulcers, certain forms of impotence, as well as a variety of other things. Approaches to warming cold tissue including cold hands, fingers, feet and toes constitute one section of the prior art. Many persons suffer from cold hands, feet or other body parts. This is often caused by insufficient blood flow in the cold tissue. Previously cold hands or feet have been treated by wearing warm socks or gloves, sometimes even socks or gloves which are mechanically heated. The use of hot packs and glove or shoe inserts which generate heat through chemical reactions has also been a potential solution. Certain liniments which are essentially irritants, such as those containing the red pepper derived substance, capsicum fall into this category. More recently, topical creams containing nitroglycerine have been used. See H. Natsuda et al., Ryumachi 34, 849 (1994). All of these approaches work at one level or another though are often extremely transient in nature. Nitroglycerine creams also have the disadvantage that nitroglycerine is a cardioactive drug, raising concerns of effects on the heart.

It has been recognized that deficiencies in blood flow in the scalp occur in male pattern baldness. See G. Duplechain et al., J. Lousiana State Med Soc. 146, 7 (1994); P Klemp et al., J Invests Dermatol 95, 725 (1989); S Toshitani et al., J Dermatol 17, 240 (1990). Topical minoxidil has been used as an agent for hair growth in male pattern baldness with varying results. Though the suggestion has been made that minoxidil operates through increase in the blood supply to the scalp, many investigators have failed to show such an effect. See E de Boer et al., Acta Dermato- Venereoligica 68, 271 (1988); C Bunker et al., British J Derm 117, 668 (1987).

 

[bornthisway]

The fundamental fact that cold tissue of the hands, fingers, feet and toes as well as other cold tissue is caused by insufficient blood flow to the tissue has been suggested. It has further been suggested by some that the use of increased blood flow through relaxation of blood vessels, particularly small and very small vessels may be of use in warming cold tissue. However reasonable this suggestion, many attempts to demonstrate warming by use of agents which produce vasodilation and therefore increased blood flow have produced negative results. See N Dietz et al., J Appl Physiol 76, 2047 (1994); S Whitmore et al., J Rheumatol 22, 50 (1995); S Singh et al., Eur J Clin Invest 25, 182 (1995). The only report of modest temporary success involved the use of nitroglycerine. See H Natsuda et al., Ryumachi 34, 849 (1994). The use of the nitric oxide precursors such as L-arginine to produce warming secondary to vasodilation has been suggested. And a variety of indirect and non-definitive experiments have been conducted using oral administration. See M. Sonntag et al., Pflugers Arch 420, 194 (1992); A. Agostoi et al., Int J Clin Lab Res 21, 202 (1991). Thus, while the literature contains suggestions that vasodilation by administration of oral L-arginine, the precursor of nitric oxide (endothelium ependent relaxing factor), no reports exist of success in producing warming of tissue using this agent. In fact Dietz (see N Dietz et al., J Appl Physiol 76, 2047 (1994)) concludes from his data that "These data suggest that NO (nitric oxide) does not play a major role in cutaneous vasodilation during body heating in humans." Further Singh (see S Singh et al., Eur J of Clin Invest 25, 182 (1995)) in a study of patients with Raynaud's phenomenon (severely cold hands and/or feet) concludes that L-arginine failed to cause vasodilation (and therefore warming) in patients with Raynaud's phenomenon.

The literature contains no suggestions or examples of the use of L-arginine in any mode of administration for the growth of hair in male pattern baldness, healing of ulcers of the skin, impotence or for any other purpose.

It has long been recognized that impaired blood flow to the penis is a major cause of erectile failure (impotence) in men. See A Moradian et al. Am J. Med 85, 748, (1988); T Hwang et al. J Formosan MedAssoc 89, 992 (1990). Further it has been recognized by using isolated tissue in vitro and in animal experiments that nitric oxide is an important mediator of relaxation of the vessels in penile cavernous tissue. See H Kirkeby et al. Acta Physiol Scand 149, 385 (1993). Topical nitroglycerine has been used in the treatment of impotence because of its ability to dilate vessels. The results were inconclusive and the treatment not well tolerated because of the cardiac response to nitroglycerine. See S Negelev J Urology 143, 586 (1990).

It was discovered that topical application of the nitric oxide precursor, L-arginine, in its various forms including orally alone or in conjunction with a variety of topical preparations, either by themselves or with other agents to aid in penetration such as a high ionic strength environment, neutralization of its charge in a complex or by other means, or included in a liposome or other biological carrier, when administered to cold or cool tissue causes a substantial and prolonged warming effect in the tissue, grow hair on bald scalp, facilitate healing of superficial ulcers such as leg ulcers and overcome impotence in many subjects.

In accordance with that invention, oral arginine by itself or in combination with a penetrating cream containing L-arginine at a concentration sufficient to produce an effect and sodium chloride or other salt at a concentration sufficient to create a hostile biophysical environment for the L-arginine in the cream is applied to the cold or cool tissue alone and/or in conjunction with oral arginine, exerts a warming effect which is prolonged, often lasting from 2-18 hours. In persons with very cold tissue (for example 22.degree. C.) this warming effect can have a magnitude of 10.degree. C. or more.

Further, in accordance with this invention, oral L-arginine alone or in conjunction with a penetrating cream containing L-arginine in a concentration sufficient to produce the desired effect along with sodium chloride or other salts at a concentration sufficient to produce a hostile biophysical environment when applied to bald areas of the scalp nightly either alone and/or in conjunction with oral arginine, produced growth of new hair within one month and substantial growth of hair within 3-4 months.

Yet further, in accordance with this invention, oral arginine alone or in conjunction with a penetrating cream containing L-arginine in a concentration sufficient to produce the desired effect along with sodium chloride or other salts at a concentration sufficient to produce a hostile biophysical environment when applied locally as the cream directly to the penis either alone and/or in conjunction with oral arginine, was effective in overcoming impotence.

Consequently, with the discovery of the present invention, a means to warm cold and cool tissue, a problem shared by many, was developed for improving this uncomfortable and often painful problem in human health has been found. Further with the discovery of the present invention, a means to restore hair growth on a bald portion of scalp has been found. Still further, with the discovery of the present invention, a means effect healing of superficial ulcers such as leg ulcers has been found. Yet further, with the discovery of the present invention, a means to overcome impotence in many men has been found.

These and other objects and features of the present invention will become apparent to those skilled in the art from reading the description of the invention, which follows.

SUMMARY OF THE INVENTION

Accordingly, several objects and advantages of the instant invention are to warm cold tissue in hands, feet or other tissue by increasing blood flow in the tissue means of enhancement of the body's natural mechanisms. It is further an object and advantage of the instant invention to prophylactically prevent tissue from becoming cold by use prior to entering into situations which induce cold hands and feet such as skiing or other winter outdoors activities. It is further an object and advantage of the instant invention to induce the growth of hair on bald portions of human scalp by means of enhancement of the body's natural mechanisms. It is yet another object of the instant invention to induce healing of superficial ulcers of the limbs by means of enhancement of the bodys natural mechanisms. It is still further another object of the instant invention to provide a means for overcoming impotence in many men.

In preferred embodiments, the delivery vehicles are capsules or tablets containing L-arginine used alone or in conjunction with a penetrating cream. In the cream the L-arginine is present as L-arginine hydrochloride in a concentration sufficient to produce the desired effect and the agent which creates the hostile biophysical environment is sodium chloride at a concentration sufficient to aid in tissue absorption.

PREFERRED EMBODIMENTS

The preferred embodiment consists tablets or capsules containing 200-500 mg of L-arginine to be used alone or in conjunction with a base cream with the properties of excellent absorption into the skin which also contains L-arginine hydrochloride (15% w/v) and sodium chloride (10% w/v). The components of the base cream may be those commonly found in hand creams. The purpose of L-arginine hydrochloride is to provide a precursor to the molecule, nitric oxide, NO. The purpose of the sodium chloride is to provide a high ionic strength environment for the highly charged molecule, L-arginine. The base cream containing L-arginine and sodium chloride is the agent which is applied to the hands and/or feet to produce to produce a warming effect in the tissue, to produce hair growth or to effect healing of ulcers such as leg ulcers, or directly to the penis in order to aid in overcoming impotence.

 

[bornthisway]

The treatment consisting of oral administration of capsules or tablets containing Larginine used alone or in conjunction with the cream acts effectively to warm cold tissue such as hands, fingers, feet, toes or other tissue when applied to the tissue and rubbed into the tissue to assure maximal absorption. The warming effect, caused by increased blood flow in the tissue is not instant but begins within 5 to 20 minutes. The effect is long lasting. Often the tissue remains warm for more than 2 to 18 hours. The treatment consisting of oral administration of capsules or tablets containing L-arginine used alone or in conjunction with the cream acts effectively to induce hair growth on bald human scalp when applied nightly to the bald area each night for several months. Hair growth is naturally a slow process. However, substantial hair growth is achieved over large areas of scalp with results becoming evident in a few weeks and substantial within several months. The cream further acts to promote healing of superficial ulcers such as those sometimes found on the legs of persons with severe diabetes. Application twice daily for a period. of two weeks causes substantial healing and in many cases complete healing is achieved within this time period or slightly longer (3-4 weeks). Further the treatment consisting of oral administration of L-arginine used alone or in conjunction with the cream when carried out daily for a period of 7-10 days and then maintained with daily administration causes substantial relief from impotence in many men.

Other Embodiments

Other Active Agents

While L-arginine hydrochloride is the preferred active agent because it is the agent in nature itself, it is non-toxic, is highly soluble and it is inexpensive, other agents could be used which are also precursors or donors of nitric oxide. These include the salt, arginine glutamate, the salt, arginine butyrate, and esters of arginine such as arginine ethyl ester or arginine butyl ester as well as other donors of nitric oxide. In the case an alternative active agent were used it would be simply substituted for L-arginine in a delivery preparation and the preparation used as in the case of the L-arginine preparation.

Other Means of Effecting Absorption

A variety of means for effecting absorption of the active agent from the topical cream might be envisioned. One principle behind the absorption of a highly charged molecule such as L-arginine into tissue is to either create a biophysically hostile environment in the delivery vehicle such that L-arginine would prefer to be in tissue, or to package L-arginine in such a way that it is carried into tissue or neutralize its charge by derivitization or forming a neutral salt. Examples of biophysically hostile environments, include but are not limited to, high ionic strength, high or low pH, and highly hydrophobic environments. Examples of packaging which would be carried into tissue includes liposomes or emulsions of collagen, collagen peptides or other components of skin or basement membrane. Examples of neutralization of charge include the salt, arginine glutamate which is electronically neutral.

In each case of creating a hostile biophysical environment for the active agent, the agent was added to an appropriate preparation. In the case of creating a high ionic strength ions such as but not limited to sodium chloride, potassium chloride, choline chloride, lithium chloride, alone or in combination were added in high concentration. Other highly charged molecules such as polylysine, polyglutamine, polyaspartate or copolymers of such charged amino acids may be used to create the hostile biophysical environment. Alternatively a hostile biophysical environment may be created by placing the highly charged L-arginine in an hydrophobic, oily environment such as in an oil-based cream containing little or no water.



EXAMPLE 1

In this example a person with very cold fingers was provided with the above warming cream consisting of a delivery vehicle of penetrating cream, L-arginine hydrochloride (15% w/v), and sodium chloride (10% w/v). The surface temperature of the subject fingers of the left hand varied from 21 to 24.degree. C. The warming cream was applied through rubbing into the skin. Surface temperatures of each finger were measured each 15 minutes for the initial hour. At 15 minutes following administration of the warming cream the effect had begun to occur with surface temperatures or various fingers rising to 26 to 29.degree. C. The maximal effect was reached by 45 minutes with surface temperatures of various fingers becoming 31 to 34.degree. C. The effect was sustained at least 4 hours.

EXAMPLE 2

In this example a 53 year old man with baldness consisting of a severely receding hairline as well as large "bald spot" on the top rear of his head was provided with a penetrating cream containing L-arginine hydrochloride (15% w/v) and sodium chloride (10% w/v). The cream was applied to the bald areas each night before going to bed and was rubbed in extensively for maximal absorption. New hair growth was noted within 2-3 weeks. Within 4 months the receding hairline (previously 4 cm of bald skin) had returned to normal and the "bald spot" previously more than 7 cm in diameter had been reduced to an area of less than 2 cm with even this area showing some new hair growth.

EXAMPLE 3

In a 54 year old man with a history of impotence administration of 1.5 g L-arginine daily in the form of oral capsules combined with twice daily administration of a penetrating cream containing L-arginine hydrochloride (15% w/v) and sodium chloride (10% w/v) directly to the penis for 7 days brought initial relief from the symptoms of impotence and allowed the subject to resume normal sexual activity.

This relief of symptoms was maintained by continuation of the treatment daily.

Accordingly, it can be seen that in the present invention I have provided a method and agents, which when applied to cold, and often painful tissue, an increase in skin temperature results through utilization of one of the body's own mechanisms for producing warmth. This effect is achieved by providing the biochemical substrate at the local site from which the controlling substance, nitric oxide, is produced. Nitric oxide causes increases in local blood flow which results in warming. Further, it can be seen that in the present invention I have provided a method and agents which when applied to bald scalp causes hair growth through utilization of one of the body's own mechanisms. This effect is achieved by providing the biochemical substrate at the local site from which the controlling substance, nitric oxide is produced. Nitric oxide causes increases in local blood flow which enables the growth of hair. Still further it can be seen that in the present invention I have provided a method and agents which when applied to leg ulcers cause healing through use of the body's own mechanisms. Yet still further, it can be seen that in the present invention I have provided a method and agents which when applied to a person with impotence causes overcoming of impotence by use of the body's own mechanisms. This effect is achieved by providing the biochemical substrate at the local site from which the controlling substance, nitric oxide is produced. Nitric oxide causes increases in local blood flow allowing the body's own healing cells and substances to reach the ulcer site.

Although the description above contains many specificities, these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the presently preferred embodiments of this invention. Various other embodiments and ramifications are possible within this scope. Thus the scope of the invention should be determined by the appended claims and their legal equivalents, rather than by the examples given.

 

[bornthisway]

I found this off of Regrowth, linked to BodyBuilding.com. Has anyone looked into this? The bald man (53 years of age) example had regrowth in 2-3 weeks, and hair line restoration in 4 months.

 

[indie85]

um, wow. If that example is for real...
Thats like up there with NEOSH101, but we can do this now...
I am tempted to try this, is there a good cream base thats not greasy? We can purchase salt and l-arginine easily 75mls of the cream, add 15 ml of l-arginine, 10ml of salt.
Only 4 weeks and signs of growth? wow, should be pretty quick to see if it works.

 

[Durandel]

I think there's already a couple of products that match this description, though not advertised for hairloss. Would either of these do the job?

http://www.amazon.com/Dorian-Yates-Appr ... B000G6870I
http://www.amazon.com/dp/B000ETNCS4?smi ... nkCode=asn

To be honest I'm almost tempted. If it works (ha ha ha) it'll be cheap to use and treatment can be stopped/reduced after regrowth. It might be worth a shot?

 

[bobs]

I'd sure like to see pics of that 53-year old man + more pics.
But it does seem promising. I'll check the other forums to see what they got on it.

 

[RaginDemon]

I'd sure like to see pics of that 53-year old man + more pics.
But it does seem promising. I'll check the other forums to see what they got on it.

Me too, I'd like to see some proof, it sounds way too good to be true.

 

[bornthisway]

The post was at least two years old on BodyBuilding.com... I figured someone would have tried this by now, but it was just recently mentioned on regrowth.. someone want to try using it for 3 or 4 weeks and let me know if it works. Or a local store I can buy it from maybe? I just bought VICCO Tumeric tonight (from a local middle eastern/indian store) which is a product mentioned lately on many hair loss forums.. I applied it to my scalp (and it does get on the hair.. I just rub it against the scalp then...) and left it on for over a hour, it washed out easily, no burning sensations or stinging, no staining... makes me wonder if it isn't powerful enough.. other people who used tumeric mentioned staining/stinging I think..

The product label is below:

Contents: Extract of tumeric 12% w/w
Excipients: q.s.
(In a non greasy base)
http://www.viccolabs.com

 

[Durandel]

I might buy some NO Infuse later this week and try it on my fully bald receded areas. That way there's no risk of shedding and any results (ha ha) will be indisputable.

I'm pretty new to the getting fit but work out most mornings now, so maybe I could try using it in conjunction with morning exercise as well as overnight. I don't know if any treatments have been evaluated in conjunction with increased cardio activity.

Even if it doesn't work for hair loss (virtual certainty) it might still come in handy for muscle recovery after the gym. God knows I could use some help there - it feels like someone's beaten me up right now.

 

[michael barry]

I have plenty of hair on my fingers and toes. Im hairy all over my body except the palms of my hands and the soles of my feet. Nitric Oxide sure as hell isn't keeping hair from growing on the backs of my hands and the tops of my feet despite the fact that I dont have good circulation in my hands and feet and they get quite cold at night and take a few minutes to "wake up" in the morning.


Ive read quite a few baldness hairloss patents. If you want to read a howler, look up the patent for castor oil and hairloss. Even though castor oil may/may not be beneficial, the reasoning behind the patent is ludicrious and sounds like the old anti-shampoo-GIB.us arguments---stress, modern life, chemicals all are the reasons we bald, etc. I was astounded reading that stuff in a patent application.


Arginine is in one of Dove's shampoos, as well as Peter Proctor's NANO. Its beneficial for hair growth, no doubt. Its also in a few other hairloss products whose ingredients Ive read------I think either Avacor or Hair Genesis. Im sure it helps get nitric Oxide to peripheral tissues and that would induce capillaries to grow as far as they could, despite years of apoptosis in the area, etc.



However, THIS:

EXAMPLE 2

In this example a 53 year old man with baldness consisting of a severely receding hairline as well as large "bald spot" on the top rear of his head was provided with a penetrating cream containing L-arginine hydrochloride (15% w/v) and sodium chloride (10% w/v). The cream was applied to the bald areas each night before going to bed and was rubbed in extensively for maximal absorption. New hair growth was noted within 2-3 weeks. Within 4 months the receding hairline (previously 4 cm of bald skin) had returned to normal and the "bald spot" previously more than 7 cm in diameter had been reduced to an area of less than 2 cm with even this area showing some new hair growth

......................................................................Doesn't mean anything without a picture. Tons of hairloss patents CLAIM to have been tested on one or two people and they always clairm regrowth, but they hardly ever post before and after photographic evidence, and if you think about it, that would be the best damn proof they could provide. One good picture of a bald spot filling in, and anyone thumbing through the patents would be almost guarnteed to read the patent through. But they hardly ever show you one, they just claim that someone regrew hair. Its infuriating.




My take, if hairloss or baldness was caused by lack of oxygen to peripheral tissues, hair transplants would not work but for a decade or so, and then the hair would fall out. But we know that doesn't happen as men who have had transplants back from the seventies and eighties still have all that plug hair growing up there, many times looking ridiculous and underneath toupees-----but still there. Lack of oxygen up front doesnt' effect them at all. The plug hairs cycle and go to the top of the dermis like any hair does, and then dive back down at the beginning of the next anagen phase and grow and grey or not grey just like the hair back in the donor area. Its characteristics in terms of circumference and color match the donor area exactly. Thirty years after the transplant................................baldness is in the hairs themselves, thats my take. Not the scalp.

 

[indie85]

Its been in shampoos and such, but has it ever been in a topical that you actively rub in and leave to absorb ala minoxidil? And to this concentrate in ionic delivery environoment?
I have only found one guy who has tried this on regrowth and he said he got peach fuzz regrowth but did not like the DMSO base he used so he stopped.
There must be a cream base thats not greasy.
I am tempted to try this purely by the timeline given -4 weeks sign of regrowth, it must be VERY powerful acting to promote growth in that time. Should be plainly obvious if it is working or not.

 

[Durandel]

My take, if hairloss or baldness was caused by lack of oxygen to peripheral tissues, hair transplants would not work but for a decade or so, and then the hair would fall out. But we know that doesn't happen as men who have had transplants back from the seventies and eighties still have all that plug hair growing up there, many times looking ridiculous and underneath toupees-----but still there.

Translanted folicles are taken from strong areas and so don't have the vunerability, so they survive in the "desert" areas. To me that says that for male pattern baldness sufferers the hairs in particular areas of the scalp either are or become vunerable to negative influences (ie DHT) as we get older. So the problem is in the hair folicle, but the cause of that problem may be elsewhere.

I don't think we're born with special areas of hair that's genetically pre-programmed to fall out at the first whiff of DHT. Instead, I think male pattern baldness is the result of a weakness in folicles imposed by indirect physical factors as we develp into adults. A genetic tendency toward a tighter scalp resulting in tissue compression, for example?

So (possibly): naturally tight scalp = compacted blood vessels = less oxygen/repair/nutrition = cumulative folicle damage = eventual male pattern baldness. By the time we start actually losing hair it's too late. The folicle is already irrepairably screwed so improving vascular activity and/or stimulating growth has little or no effect for most people. Whatever regrowth is achieved is dependent on perpetual treatment to keep the damaged folicle active.

To me that'd explain the patterns of baldness, explain why increasing the blood flow doesn't generally work, explain why the various other treatments are so hit & miss, explain why treatments have to be endlessly maintained, and explain how male pattern baldness is inheritied.

According to my theory the only really effective and sustainable solution is to grow or relocate healthy folicles, rather than endlessly trying to regrow and maintain the existing irrepairably damaged folicles. That's where hair transplant or HM would come in.

That's the way I see it, anyway. Of course, I could be horribly wrong.

 

[michael barry]

I don't think we're born with special areas of hair that's genetically pre-programmed to fall out at the first whiff of DHT. Instead, I think male pattern baldness is the result of a weakness in folicles imposed by indirect physical factors as we develp into adults. A genetic tendency toward a tighter scalp resulting in tissue compression, for example?

NOPE>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

Dr. Norman Oreintriech took hair FROM AN INCH BEHIND THE RECEEDING HAIRLINE AND TRANSPLANTED THEM TO THE BODY almost fifty years ago. Guess what? They began to miniaturize later when the hairs up on the head began to miniaturize that were formerly around them. The conclusion is that the haircycle clock keeps time no matter where the hairs are moved to.


When you are a fetus, in your moms first trimester, the skin grows over the scalp in just about the classic norwood pattern. Its in this time that scientists say that the individual hairs see their genetic response to male hormone be written in stone genetically. Balding men have less blood flow and less oxygen in their balding areas. "Tight" scalp might be from excessive collagenous deposition (which helps protect against sun damage to the skin in bald scalp and might very well have a purpose) might add to the "tightness" of the scalp, but there is no evidence that pre-bald and balding men have higher blood flow or any more tension in their scalps than anyone else. Nada.


Its "in the hairs" themselves, and that was determined in fetal development JUST LIKE THE RESEARCHES SAY.

 

[Durandel]

Shame. My theory seemed so neat and rational too. I'm still a bit confused though.

You're agreeing that "balding men have less blood flow and less oxygen in their balding areas", but saying that this is irrelevant because areas of scalp hair are genetically pre-determined to miniaturize away according to a personal haircycle clock? So are you then saying that male pattern baldness entirely testosterone driven and therefore the hair loss of those "suicide folicles" is inevitable without cutting back the very thing that makes us men?

I don't fancy that at all. Even if more zero-side-effect DHT treatments come out, to me it all seems to come down to the same thing. Either (a) endlessly try to keep failed & failing folicles active, or (b) replace the failed folicles by implanting or seeding healty ones.

Am I wrong?

 

[michael barry]

http://www.drvogelplasticsurgeon.com/bna/hair_08.html


I want you to look at that photo and think to yourself for a few seconds. That man had a hair transplant in the eighties (plug style done back then----awful looking). He balded over the next two decades through the plug field and now they stick out like a sore thumb, but they still grow and have the same color, texture, curl or no curl that the hair in the very back of the head has.


Here is another guy with the same situation, except you can still see the miniaturizing hair in the front thats going, http://www.drvogelplasticsurgeon.com/bn ... duce3.html , but isn't all gone yet.


Here is a whole page of similar repairs, http://www.drvogelplasticsurgeon.com/hair transplant ... corrective




Here is a picture of CHEST HAIR growing dark on a scalp of grey hair, http://www.fusehair.com/Bodyhairtransplant/Inlarge.htm

That is a picture of BLACK BODY HAIR that has been transplanted from the patients body to the scalp. It RETAINS ALL OF ITS INDIVIDUAL CHARACTERISTICS once placed on the scalp. Curl, calibre, color are the same. Hopefully, the growth phase length will elongate and the hair can attain roughly twice its usual length, but this only happens about half the time.

Body hair transplants have been good for one thing: showing that androgenic alopecia is "in the hairs" and not "in the scalp". Hair can grow fine on bald scalp if taken from somewhere else on the same human being.


Here is the info page on body hair transplants (which usually look pretty weak in my opinon because body hair is seldomly as good as head hair in appearance and thickness or size of follicular units), http://fusehair.com/Body%20hair%20transplant.htm




If lack of oxygen in balding scalp is what "flipped" head hairs response to androgens.............................then over time the transplanted hair would become susceptible to them also. The thing is that we have some men who had transplants in the 70's. Its been 35 years since their transplants, and the hair is growing up front just like it did back then-----it looks just like the hair in color, thickness, curl, health that is in the back of the head in the "donor area". The thing is though, most peope dont have enough donor hair to adequately cover the classic NW6 level bald area without looking "thin" up top or having to thin hair on the back and sides.


If you have any doubt about testosterone and its more bind-happy metabolite Dihydrotestsoetrone's direct effect on hair (by the way, DHT binds twice as readily to the androgen receptor as T, and has a five times slower dissassociation rate from the receptor, so it stays bound much longer and elicits the mitochondrial DNA response downstream of its transcription which is bad in head hair), look at this research from the University of Jena in Germany: http://alpecin.com/en/pdf/alpecin_research_3.pdf

Hairs given testosterone in test tubes that are from male pattern baldness-areas grow slower and more weakly. The same hairs from the male pattern baldness-area not given testosterone grow strongly.


We have discussed a mouse study on this site a year or two ago that took vellus hairs from male pattern baldness areas of balding men and put them on the backs of immuno-deficient mice. The vellus hairs grew as well in 22 weeks as hairs from the donor area of the same men that were also transplanted to the mice. There is an immuno component to balding if you didn't know. The testosterone gets the hair to grow more weakly, and then something about the negative growth factors secreted by the dermal papilla elicits an immune system response and the immunse system begins to attack the hair with varrying intensity as it apparently percieves the hairs as foreign bodies. However, the mouse study showed that vellus hairs, in the absence of testosterone, apparently have rejuvanitive capabilities. But finding an alpha five inhibitor for DHT and a receptor blocker that utterly and totally stops all male hormone (testosterone, androstenidione, DHEA, DHEAS, etc.) from binding is a pretty tall order. Nothing is probably that potent without side effects.


Waiting on cloning like everyone else........................................sigh

 

[michael barry]

................one more thingy, on oxygen levels and bald scalp et cetera. If you have a ton of hairs growing in an area, they all have capillary networks reaching down in the skin getting nourishment. This is much like a forrest of trees having root systems that go down far in the earth vs. a field of grass (vellus hair) that have small root systems that go down less than a foot. Of course there will be less blood up there and blood is what carries hemoglobin, which is what carries oxygen in that same blood. None of this is a suprise. Said that for years.

 

[bornthisway]

I still don't see why we're comparing NO2 on the hand with NO2 on the head? Since, hair loss doesn't occur on the hand, maybe the scalp is more blood flow/oxygen/whatever deprived due to the fact of gravity and whatever else.. I'm just making stuff up here but at the least I'd guess it's worth a try. If NANO has it, there probably is a good reason for it. Though, aside NO2, what are the opinions of VICCO's Tumeric 3 times a week?

 

[harold]

Shame. My theory seemed so neat and rational too. I'm still a bit confused though.

You're agreeing that "balding men have less blood flow and less oxygen in their balding areas", but saying that this is irrelevant because areas of scalp hair are genetically pre-determined to miniaturize away according to a personal haircycle clock? So are you then saying that male pattern baldness entirely testosterone driven and therefore the hair loss of those "suicide folicles" is inevitable without cutting back the very thing that makes us men?

I don't fancy that at all. Even if more zero-side-effect DHT treatments come out, to me it all seems to come down to the same thing. Either (a) endlessly try to keep failed & failing folicles active, or (b) replace the failed folicles by implanting or seeding healty ones.

Am I wrong?

There are factors that happen downstream from the androgen receptor and its binding to DHT. TGF-Beta production, Generation of ROS other inhibitory factors etc. These can all be altered (in theory) without the need to involve DHT. We have known this for ages - if DHT was "poison" for hair then men would not have beards and hairy chests.
hh

 

[michael barry]

Body and scalp hair are different as experiments prove conclusively.


No male hormone is necessary for head hair to grow just fine. I grows super well without it. Ask Bryan, as he's posted some of the experiments for years.


Body hair however, and especially beard hair, has to have male hormone. It will not grow without it.




The University of Jena in Germany took 600 follicles from balding men and tested caffeine against testsoterone, etc. They did use some control hairs and some hairs with just testosterone. Hairs with testosterone grew much more weakly. These are whole human hairs from thinning areas. Without the big T, they grew like any other hair would......................just fine.



The dermal papilla in male pattern baldness-hairs releases growth inhibitors. Some of which are known. One new one, that caffeine appears to bind, is called DKK-1, which suppresses the expression of any wnt which might be important, or not. TGF_beta is another, thrombospondin, FGF-5, and a few more. We dont know if we have discovered them all, but we do know that these substances slow cell growth in various hair cells through expermints with dermal papilla cells (which release the negative growth factors) and other cells of the hair follicle (epilithial, outer root sheath, keratinocyte, inner root sheath, etc.)

DHT- binds twice as readily to the human androgen receptor as Testosterone does, but has a FIVE TIMES SLOWER dissassociation rate. Testosterone has been shown by me via many photographs of Female-to-male transexuals to rapidly age the face and hair (and bald the heads of people genetically predisposed).


I suppose one could inhibit all the negative growth factors released by the dermal papilla with a TGF-beta inhibiting topical, caffeine topically, tocopherol or grape seed proanthocyandins for Protien Kinease C, Green tea for TNF-alpha, but one is stilll stuck with thrombosponding and FGF-5 to deal with. Would that be enough to keep the hair? Would the immuno attack still happen.

I'd love to see someone try to take this kinda approach and take good before and after photographs. I dont just LOVE taking finasteride, but hell, I know it works and have studies and pictures of study participants to back it up. Dutasteride, according to Korean scientists who studied it for baldness, appears to stop all hairloss and ever regrows a tid-bit of hair alone.


My personal opinion is that in some of us, DHT slows hair growth and an overabundance of one or two of the negative cytokines get the immune system to react to the hair as a foreign body, and the immuno attack and the natural effect of Testosterone on skin ages the area of the follicle and the dermis pretty badly. But we know spironolactone helps slow baldness (Bryan has a picture), and Ive seen three pictures of fluridil regrowth (one on a buzz cut that is pretty impressive)-----so we can say with certainty that just inhibiting androgen uptake at the receptor apparently keeps the downstream bad things from happening. Whats not to like about that except for the general pain-in-the-butt of having to deal with a topical?


Here is a little pub med on fluridil, a receptor blocker designed to degrade in water and that showed no side effects or absorption, http://www.ncbi.nlm.nih.gov/sites/entre ... stractPlus


Here are some pics, http://www.menspharma.com/results.htm
The first and third one are impressive to me. The third one shows frontal regrowth, which is damn hard to get. But maintenance from fluridil would seem pretty damn likely based on that.......................................and it just blocks or downregs the human androgen receptor. Someone adding finasteride on top of it might really see some impressive results over a few years.