Methods of treatment comprising administration of Substance P

Details Methods of treatment comprising administration of Substance P Methods of treatment comprising administration of Substance P

2000-11-28

2002-08-20

Carlson, Karen Cochrane (Department: 1653)

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

11 to 14 amino acid residues in defined sequence

C530S327000, C530S300000, C514S002600, C514S015800

Reexamination Certificate

active

06437093

ABSTRACT:

BACKGROUND OF THE INVENTION
Substance P is a protein naturally occurring in the body. It is a tachykinin which induces contraction of smooth muscle and appears in humans and other mammals at highest concentrations in brain, intestine, spinal ganglia.
Since the late 1970's, studies have shown that Substance P has a variety of biological activities including acting as a vasodilator, stimulates salivation, can cause increased gut permeability. Of particular interest to the present invention is the observation that Substance P can, at different concentrations, cause analgesia or hyperalgesia. Although its biological activity can be difficult to measure, its activity as a systemic signal is highly stable at ambient and refrigerated temperatures.
Substance P can act as a neurotransmitter or a hormone (particularly in the gut as a hormone). The vasodilation caused by Substance P is a result of its direct inhibitory effect on arteriolar smooth muscle. This effect is mediated by receptors. that appear specific to Substance P versus other vasodialators. Of interest to the present invention is that those receptors appear to be identical to those specific for rubeola virus. While Substance P inhibits contraction of arteriolar smooth muscle, it stimulates contraction of intestinal, bronchial and venous smooth muscle. Substance P can also cause diuresis and natriuresis in kidneys. These observations suggest that there could be more than one type of Substance P receptor.
SUMMARY OF THE INVENTION
The present invention relates to the observation that Substance P appears to be a signal for the mediation of neurogenic pain and that it would appear to be a candidate as a therapeutic agent for those types of pain which are most difficult to control, especially peripheral neuropathy.
The present invention provides methods for treatment of disease states selected from the group consisting of respiratory dysfunction and pain comprising administration of an effective amount of Substance P. The invention also provides pharmaceutical compositions for treatment of respiratory dysfunction and pain comprising an effective amount of Substance P in combination with a suitable carrier.
It is believed that Substance P may function in the treatment of pain by having a direct effect on pain receptors. Moreover, while not wishing to be bound by any particular theory of the invention, Substance P may operate in treatment of certain respiratory conditions such as Reactive Upper Airway Dysfunction (RUDS) through a mechanism of treatment of neuropathy. Specifically, RUDS has been described as a cranial nerve neuropathy involving the 10th cranical nerve (vagus). Accordingly, it may be that Substance P treats respiratory conditions such as RUDS through a mechanism which treats neuropathies associated with those diseases.
An effective amount of Substance P according to the invention is an amount which results in a reduction in the symptoms of a respiratory disease or of pain symptoms. Amounts of Substance P ranging from 10
−7
to 10
−2
mg are contemplated to be effective according to the invention. While preferred dosages include those ranging from 10
−5
to 10
−4
mg Substance P and 8×10
−5
mg has been found to be particulary effective when administered from one to six times daily in the form of sublingual drops, those of ordinary skill would be capable of adjusting the dosage amounts and schedule by observation of the effectiveness of treatment. Accordingly, it is contemplated that the range in dosage for the application could be several logs higher or lower than the optimum above. While the preferred route of administration is sublingual administration, it would be apparent to those of skill in the art that other routes would also be suitable for treatment according to the invention including subcutaneous administration, intramuscular, intravenous administration and the like. The invention also provides pharmaceutical compositions for treatment of respiratory conditions and pain comprising Substance P in combination with a suitable carrier such as saline or other pharmaceutically acceptable excipients.


REFERENCES:
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patent: 5633232 (1997-05-01), Matsuo et al.
patent: 5945508 (1999-08-01), Witten et al.
Frederickson et al., Dual Actions of Substance P on Nociception: Possible Role of Endogenous Opiods. Science 199, 1359-1362 (1978).*
Oehme et al., Substance P: Does It Produce Analgesia or Hyperalgesia? Science 208, 305-307 (1980).*
Cross et al., “Further characterisation of substance P induced histamine release from human bronchoalveolar lavage mast cells”Inflamm Res 45, Supplement 1:S11-S12 1996.
Henry, “Substance P and inflammatory pain: potential of substance P antagonists as analgesics”,Inflammatory Disease Therapypp. 75-87 (1993).
Meggs, “Rads and Ruds—The toxic induction of asthma and rhinitis”,Clinical Toxicology, 32(5), 487-501 (1994).
Tomlinson, et al., “Neurotrophins and peripheral neuropathy”,Phil. Trans. R. Soc. Loud, B351 455-462 (1996).

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