Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2000-12-11
2002-10-01
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C424S401000, C424S439000, C424S450000
Reexamination Certificate
active
06458841
ABSTRACT:
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).
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° C.) this warming effect can have a magnitude of 10° 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 o
Criares Theodore J.
Lorusso & Loud
New England Property Holdings, LLC
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