US20030064932A1 - Methods of treatment comprising administration of Substance P - Google Patents
Methods of treatment comprising administration of Substance P Download PDFInfo
- Publication number
- US20030064932A1 US20030064932A1 US10/223,579 US22357902A US2003064932A1 US 20030064932 A1 US20030064932 A1 US 20030064932A1 US 22357902 A US22357902 A US 22357902A US 2003064932 A1 US2003064932 A1 US 2003064932A1
- Authority
- US
- United States
- Prior art keywords
- substance
- pain
- treatment
- subject
- administration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 title claims abstract description 39
- 102100024304 Protachykinin-1 Human genes 0.000 title claims abstract description 39
- 101800003906 Substance P Proteins 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 17
- 208000002193 Pain Diseases 0.000 claims abstract description 19
- 230000036407 pain Effects 0.000 claims abstract description 19
- 208000024891 symptom Diseases 0.000 claims abstract description 8
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 230000004064 dysfunction Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 206010011224 Cough Diseases 0.000 description 5
- 230000000241 respiratory effect Effects 0.000 description 5
- 210000002460 smooth muscle Anatomy 0.000 description 4
- 230000008602 contraction Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 206010002953 Aphonia Diseases 0.000 description 1
- 206010013952 Dysphonia Diseases 0.000 description 1
- 208000010473 Hoarseness Diseases 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 208000035154 Hyperesthesia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 description 1
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000003141 Tachykinin Human genes 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000014826 cranial nerve neuropathy Diseases 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000773 effect on pain Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 210000000929 nociceptor Anatomy 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000012495 positive regulation of renal sodium excretion Effects 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/046—Tachykinins, e.g. eledoisins, substance P; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
Definitions
- 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.
- Substance P has a variety of biological activities including acting as a vasodilator, stimulates salivation, can cause increased gut permeability.
- Substance P can, at different concentrations, cause analgesia or hyperalgesia.
- 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.
- 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.
- 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.
- RUDS Reactive Upper Airway Dysfunction
- 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.
- 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.
- the subject was treated by sublingual administration of Substance P according to the method of Example 1 and she experienced almost immediate pain relief. As a result, the subject was able to discontinue narcotics, and continues well with continued Substance P treatment.
- a 44 year old female presented with a diagnosis of chronic sciatic pain that was disabling and of several years duration.
- Analgesics helped reduce the pain.
- the subject was treated by sublingual administration of Substance P according to the method of Example 1.
- the first sublingual drop of Substance P instantly and dramatically “turned off” the pain.
- the Patient continued over several months to use daily doses of Substance P with continued control of pain.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A method for treatment of symptoms of a respiratory disease or pain in a subject comprising administering to said subject a Substance P in an amount effective to alleviate those symptoms.
Description
- 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.
- 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.
- According to this example, a male presented with upper airway distress who had a persistent cough triggered by exposure to volatile chemicals. His disease appeared to be initiated by chronic exposure to floor stripper which caused RUDS (Reactive Upper Airway Dysfunction). This cough was stopped almost immediately by treatment with Substance P which was administered by sublingual drop (0.05 ml/drop) at one drop per hour for three hours and then one drop four times daily. Each drop contained 8×10 −5 mg synthetic Substance P (Sigma) in phosphate buffered saline.
- According to this example, an 8 year old boy presented with a repetitive, almost tic-like, exaggerated cough that was disruptive to his classmates and teacher. Several physicians were consulted without success and with no apparent cause found for the cough. Substance P was administered by sublingual administration according to the method of Example 1 and stopped the cough within minutes. Practice of the method of the invention continued to control this disorder after more than a year.
- According to this example, a 49 year old female presented RUDS that manifested as severe hoarseness or even aphonia if exposed to volatile chemicals, and especially to fragrances. She had suffered for several years after being exposed to fragrances from several co-workers using multiple perfumes. Her airway problem was reduced only by complete avoidance of any exposure to volatile chemicals which dramatically changing her lifestyle. Sublingual administration of Substance P according to the method of Example 1 provided significant improvement and has allowed her to return to more normal living. Her RUDS continues to be controlled by taking one drop of Substance P four times daily, or more frequently if needed.
- According to this example, a 63 year old woman presented with a history of numbness, tingling and severe pain in feet and legs eight years earlier. During the year immediately preceding her first office visit, the discomfort had spread to her hands. She had a history of familial diabetes, but she did not test diabetic. No cause of her discomfort could be determined, and the only relief she obtained was from narcotic analgesics.
- The subject was treated by sublingual administration of Substance P according to the method of Example 1 and she experienced almost immediate pain relief. As a result, the subject was able to discontinue narcotics, and continues well with continued Substance P treatment.
- According to this example, a 69 year old woman presented with severe sciatic-like pain of the hip of long duration. The subject also presented with a diagnosis of diabetes. The subject was treated by sublingual administration of Substance P according to the method of Example 1 which reduced the pain dramatically. She continues well for over two years.
- According to this example, a 44 year old female presented with a diagnosis of chronic sciatic pain that was disabling and of several years duration. Analgesics helped reduce the pain. The subject was treated by sublingual administration of Substance P according to the method of Example 1. The first sublingual drop of Substance P instantly and dramatically “turned off” the pain. The Patient continued over several months to use daily doses of Substance P with continued control of pain.
- According to this example, a 59 year old woman with arthritis-like pain and inflammation of the knuckles but who tested negative for rheumatoid factor. Pain was not significantly reduced by over the counter formulations or prescription drugs. The subject was treated by sublingual administration of Substance P according to the method of Example 1. After three days of Substance P sublingual drop therapy, the patient reported “remarkable” improvement that continued after two months.
- Numerous modifications and variations in the practice of the invention are expected to occur to those skilled in the art upon consideration of the presently preferred embodiments thereof Consequently, the only limitations which should be placed upon the scope of the invention are those which appear in the appended claims.
Claims (9)
1. A method for the treatment of symptoms of a respiratory disease or pain in a subject comprising administering to said subject a Substance P in an amount effective to alleviate those symptoms.
2. The method of claim 1 wherein said respiratory disease is Reactive Upper Airway Dysfunction.
3. The method of claim 1 wherein the disease is neurogenic pain.
4. The method of claim 1 wherein the disease is peripheral neuropathy.
5. The method of claim 1 wherein Substance P is administered by a route selected from the group consisting of sublingual administration and subcutaneous administration.
6. The method of claim 5 wherein Substance P is administered by sublingual administration.
7. The method of claim 6 wherein Substance P is administered at a dosage of from 10−5 to 10−4 mg one to six times daily.
8. A pharmaceutical composition for treatment of symptoms of a respiratory disease or pain in a subject comprising Substance P in an amount effective to alleviate those symptoms and a suitable carrier.
9. The pharmaceutical composition of claim 8 wherein the Substance P is present in a dosage of from 10−5 to 10−4 mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/223,579 US20030064932A1 (en) | 2000-11-28 | 2002-08-19 | Methods of treatment comprising administration of Substance P |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/723,699 US6437093B1 (en) | 2000-11-28 | 2000-11-28 | Methods of treatment comprising administration of Substance P |
| US10/223,579 US20030064932A1 (en) | 2000-11-28 | 2002-08-19 | Methods of treatment comprising administration of Substance P |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/723,699 Continuation US6437093B1 (en) | 2000-11-28 | 2000-11-28 | Methods of treatment comprising administration of Substance P |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20030064932A1 true US20030064932A1 (en) | 2003-04-03 |
Family
ID=24907313
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/723,699 Expired - Lifetime US6437093B1 (en) | 2000-11-28 | 2000-11-28 | Methods of treatment comprising administration of Substance P |
| US10/223,579 Abandoned US20030064932A1 (en) | 2000-11-28 | 2002-08-19 | Methods of treatment comprising administration of Substance P |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/723,699 Expired - Lifetime US6437093B1 (en) | 2000-11-28 | 2000-11-28 | Methods of treatment comprising administration of Substance P |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US6437093B1 (en) |
| EP (1) | EP1337265A4 (en) |
| JP (1) | JP3916563B2 (en) |
| AU (1) | AU2001273228A1 (en) |
| CA (1) | CA2428026A1 (en) |
| IL (1) | IL155819A0 (en) |
| WO (1) | WO2002043748A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6437093B1 (en) * | 2000-11-28 | 2002-08-20 | Milkhaus Laboratory, Inc. | Methods of treatment comprising administration of Substance P |
| EP1809104A4 (en) * | 2004-09-23 | 2009-04-29 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
| KR100593397B1 (en) * | 2004-10-27 | 2006-06-28 | 한국원자력연구소 | Wound healing or wound healing promoters containing mesodermal stem cells and / or P substances, or cell therapeutics |
| AU2007221135A1 (en) * | 2006-02-27 | 2007-09-07 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
| KR20130092470A (en) * | 2012-02-09 | 2013-08-20 | 경희대학교 산학협력단 | Composition for preventing or curing neuropathic pain comprising substance p |
| DE102014200499B4 (en) * | 2014-01-14 | 2017-03-30 | Robert Bosch Gmbh | Microfluidic system and apparatus and method for conducting fluid in a microfluidic system |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5420297A (en) * | 1990-10-24 | 1995-05-30 | Fujisawa Pharmaceutical Co., Ltd. | Peptides having substance P antagonistic activity |
| US5998376A (en) * | 1996-07-23 | 1999-12-07 | Witten; Mark L. | Substance P treatment for immunostimulation |
| US6437093B1 (en) * | 2000-11-28 | 2002-08-20 | Milkhaus Laboratory, Inc. | Methods of treatment comprising administration of Substance P |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4059693A (en) * | 1976-06-11 | 1977-11-22 | University Patents, Inc. | Analgesic action of substance P |
| US4680283A (en) * | 1984-09-26 | 1987-07-14 | Merck & Co., Inc. | Analogs of substance P and eledoisin |
| US5616562A (en) * | 1990-04-27 | 1997-04-01 | Murphy; Christopher J. | Methods and compositions using substance P to promote wound healing |
| US5137873A (en) * | 1990-07-27 | 1992-08-11 | The Children's Medical Center Corporation | Substance p and tachykinin agonists for treatment of alzheimer's disease |
| US5891842A (en) * | 1993-04-09 | 1999-04-06 | Trustees Of Tufts College | Methodology for eliciting an analgesic response in a living subject |
| US6063758A (en) * | 1997-07-09 | 2000-05-16 | Advanced Targeting Systems, Inc. | Substance P-Saporin (SP-SAP) conjugates and methods of use thereof |
-
2000
- 2000-11-28 US US09/723,699 patent/US6437093B1/en not_active Expired - Lifetime
-
2001
- 2001-07-06 JP JP2002545718A patent/JP3916563B2/en not_active Expired - Fee Related
- 2001-07-06 AU AU2001273228A patent/AU2001273228A1/en not_active Abandoned
- 2001-07-06 IL IL15581901A patent/IL155819A0/en not_active IP Right Cessation
- 2001-07-06 WO PCT/US2001/021414 patent/WO2002043748A1/en not_active Ceased
- 2001-07-06 CA CA002428026A patent/CA2428026A1/en not_active Abandoned
- 2001-07-06 EP EP01952484A patent/EP1337265A4/en not_active Withdrawn
-
2002
- 2002-08-19 US US10/223,579 patent/US20030064932A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5420297A (en) * | 1990-10-24 | 1995-05-30 | Fujisawa Pharmaceutical Co., Ltd. | Peptides having substance P antagonistic activity |
| US5633232A (en) * | 1990-10-24 | 1997-05-27 | Fujisawa Pharmaceutical Co., Ltd. | Tachykinin antagonist dipeptides |
| US5998376A (en) * | 1996-07-23 | 1999-12-07 | Witten; Mark L. | Substance P treatment for immunostimulation |
| US6437093B1 (en) * | 2000-11-28 | 2002-08-20 | Milkhaus Laboratory, Inc. | Methods of treatment comprising administration of Substance P |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3916563B2 (en) | 2007-05-16 |
| WO2002043748A1 (en) | 2002-06-06 |
| US6437093B1 (en) | 2002-08-20 |
| AU2001273228A1 (en) | 2002-06-11 |
| EP1337265A1 (en) | 2003-08-27 |
| IL155819A0 (en) | 2003-12-23 |
| CA2428026A1 (en) | 2002-06-06 |
| JP2004514698A (en) | 2004-05-20 |
| EP1337265A4 (en) | 2004-01-14 |
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