| UPDATE | 04.00 |
| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | 11.04.00 |
| PATENT TITLE |
Method of collagen therapy using relaxin |
| PATENT ABSTRACT |
A method of treating involuntary muscle dysfunctions includes administering a therapeuticaly effective amount of relaxin to a patient. Involuntary muscle dysfunctions amenable to treatment with relaxin include fibromyalgia, myofascial pain syndrome, chronic fatigue syndrome, dystonia, pelvic floor dysfunction, irritable bowel syndrome, and others. |
| PATENT INVENTORS | This data is not available for free |
| PATENT FILE DATE | 19.11.98 |
| PATENT REFERENCES CITED |
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Colon et al., "Relaxin Secretion into Human Semen is Independent of Gonadotropin Stimulation", Biology of Reporudction, vol. 50, pp. 187-192, 1994. B.A. Evans et al., "Characterization of Two RElaxin Genes in the Chimpanzee", Journal of Endocrinology, 1994, vol. 140, pp. 385-392. Mari S. Golub et al., "Effect of Short-Term Infusion of Recombinant Human Relaxin on Blood Pressure in the Late-Pregnant Rhesus Macaque (Macaca mulatta)", Obstetrics & Gynecology, vol. 83, No. 1, Jan. 1994, pp. 85-88. Eric Jauniaux et al., "The Role of Relaxin in the Development of the Uteroplacental Circulation in Early Pregnancy", Obstetrics & Gynecology, pp. 338-342 (missing pp. 339 and 341). M.R. Johnson et al., "The Regulation of Plasma Relaxin Levels During Human Pregnancy", Journal of Endocrinology, 1994, vol. 142. pp. 261-265. Bernard Lane et al., "Decidualization of Human Endometrial Stromal Cells In Vitro: Effects of Progestine and Relaxin on the Ultrastructure and production of decidual Secretory Proteins", Human Reproduction, vol. 9, No. 2. pp. 259-266, 1994. Francesco Lanzafame et al.. "Pharmacological Stimulation of Sperm Motility". Human Reproduction. vol. 9. No. 2. pp. 192-199, 1994. Lone Kjeld Petersen et al., "Normal Serum RElaxin in Women with Disabiling Pelvic Pain During Pregnancy". Gynecol Obstet Invest. 1994. vol. 38, pp. 21-23. G.N. Stemmermann et al., "Immunocytochemical Identification of a Relaxin-Like Protein in Gastrointestinal Epithelium and Carcinoma: A Preliminary Report", Journal of Endocrinology, 1994, vol. 140, pp. 321-325. L.S. Tashima et al., "Human Relaxins in Normal, Benign and Neoplastic Breast Tissue", Journal of Molecular Endocrinology, 1994, vol. 12, pp. 351-364. R.J. Winn et al., "Individual and Combined Effects of Relaxin, Estrogen, and Progesterone in Ovariectomized Gilts. I. Effects on the Growth, Softening, and Histological Properties of the Cervix", Endocrinology, 1994, vol. 135. No. 3, pp. 1241-1249. Seth Guller et al., "Negative Regulation of Placental Fibronectin Expression by Glucocorticoids and Cyclic Adenosine3',5'-Monophosphate.sup.a,b ", Annals New York Academy of Sciences, pp. 132-142, Sep. 1994. Alastair H. MacLennan et al., "Ripening of the Human Cervix and Induction of Labor with Intracervical Purified Porcine Relaxin", Obstetrics & Gynecology, vol. 68, No. 5, Nov. 1986, pp. 598-601. A.M. Poisner et al., "Relaxin Stimulats The Synthesis and Release of Prorenin from Human Decidual Cells: Evidence for Autocrine/Paracrine Regulation", Journal of Clinical Endocrinology and Metabolism, vol. 70, No. 6, pp. 1765-1767, 1990. E. Bullesbach et al., "Total Synthesis of Human RElaxin and Human RElaxin Derivatives by Solid-phase Peptide Synthesis and Site-directed Chain Combination", The Journal of Biological Chemistry, vol. 266, No. 17, Issue of Jun. 15, pp. 10754-10761, 1991. M.B. O'Day-Bowman et al., Hormonal Control of the Cervix in Pregnant Gilts. III. Relaxin's Influence on Cervical Biochemical Properties in Ovariectomized Hormone-Treated Gilts, Endocrinology, 1991, vol. 129, No. 4, pp. 1967-1976. Letten F. Saugstad, "Persistent Pelvic Pain and Pelvic Joint Instability", European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 41, 1991, pp. 197-201. Erika Bullesback et al., The Receptor-Binding Site of Human Relaxin II, The Journal of Biological Chemistry, vol. 267, No. 32, Issue of Nov. 15, pp. 22957-22960, 1992. Jeffrey A. Hall et al., "Influence of Ovarian Steroids on Relaxin-Induced Uterine Growth in Ovariectomized Gilts". Endocrinology. 1992, vol. 130, No. 6, pp. 3159-3166. Douglas Kibblewhite et al., "The Effect of Relaxin on Tissue Expansion", Arch. Otolaryngol Head Neck Surg.. vol. 118, Feb. 1992, pp. 153-156. A.B. Lee et al., "Monoclonal Antibodies Specific for Rat Relaxin. IV. Passive Immunization with Monoclonal Antibodies throughout the Second Half of Pregnancy Disrupts Histological Changes Associated with Cervical Softening at Parturition in Rats", Endocrinology. 1992. vol. 130, No. 4, pp. 2386-2391. Robin J. Bell et al., "A Randomized. Double-Blind. Placebo-Controlled Trial of the Safety of Vaginal Recombinant Human Relaxin for Cervical Ripening", Obstetrics & Gynecology, vol. 82, No. 3. Sep. 1993. pp. 328-333. Gillian D. Bryant-Greenwood et al., "Sequential Appearance of RElaxin. Prolactin and IGFBP-1 During Growth and Differentiation of the Human Endometrium", Molecular and Cellular Endocrinology, vol. 95, 1993, pp. 23-29. Sharon A. Chen et al.. "The Pharmacokinetics of Recombinant Human Relaxin in Nonpregnant Women After Intravenous, Intravaginal. and Intracervical Administration", Pharmaceutical Research. vol. 10. No. 6, 1993 pp. 834-838. C. Huang, et al., "Stimulation of Collagen Secretion by Relaxin and Effect of Oestrogen on Relaxin Binding in Uterine Cervical Cells of Pigs", Journal of Reproduction and Fertility, 1993, vol. 98. pp. 153-158. Phyllis L. Osheroff et al., "Expression of Relaxin mRNA and Relaxin Receptors in Postnatal and Adult Rat Brains and Hearts", The Journal of Biological Chemistry, vol. 268, No. 2, Issued Jul. 15, pp. 15193-15199, 1993. Pramod R. Saxena et al., "Cardiac Effects of Relaxin", TiPS, Jun. 1993, vol. 14, pp. 231-232. Don L. Goldenberg, "Medications/Clinical Trials in Fibromyalgia", Journal of Musculoskeletal Pain, vol. 2, No. 3, 1994, pp. 135-142. Frederick Wolfe, MD, "When to Diagnose Fibromyalgia", Diagnostic Issues: 20/2, 1994, pp. 485-501. Yunus et al., "Primary Fibromyalgia Syndrome and Myofascial Pain Syndrome: Clinical Features and Muscle Pathology", Arch Phys Med Rehabil, vol. 69, Jun. 1988. Bruce Rothschild et al., "Retrospective Assessment of Fibromyalgia Therapeusis", Comprehensive Therapy, 1994, vol. 20(10): pp. 545-549. Frederick Wolfe, "Post-traumatic Fibromyalgia: A Case Report Narrated by the Patient", Arthritis Care and Research, vol. 7(3), pp. 161-165, Sep. 1994. Testimony to the U.S. Senate Appropriations Subcommittee on Labor, Health & Human Services, and Education, Mar. 31, 1995. Patient Information Sheet, ILETIN.RTM. I, II, III, Eli Lilly and Company, 1989, 5 pages. Patient Information Sheet, HUMULIN.RTM. R, 5 pages, Jul. 1994. Patient Information Sheet, HUMULIN.RTM. L, 4 pages, Jul. 1994. Patient Information Sheet, HUMULIN.RTM. N, 4 pages, Oct. 1994. Patient Information Sheet, Novolin.RTM. R, 4 pages, Dec. 1993. Patient Information Sheet, Novolin.RTM. N, 4 pages, Dec. 1993. Patient Information Sheet, Catapres-TTS.RTM., 6 pages, Oct. 1992. Patient Information Sheet, Estraderm.RTM.. Rev. Dec. 1992, 2 pages. Patient Information Sheet, Transderm-Nitro.RTM. Rev. Oct. 1989, 3 pages. Patient Information Sheet, Prochlorperazine Suppositories, USP, 4 pages. Jul. 1993. Patient Information Sheet, TERAZOL.RTM. 3, Rev. Feb. 1991. Ortho Pharmaceutical Corporation, 4 pages, Feb. 1991. Patient Information Sheet, MONISTAT.RTM. 7, Rev. Nov. 1992, Advanced Care Products, 3 pages. Patient Information Sheet, Hydrocortisone Acetate Suppositories 25 mg. Paddock Laboratories. Inc., Oct. 1994. Karl G. Henriksson, "Pathogenesis of Fibromyalgia", Journal of Musculoskeletal Pain, vol. 1, No. 3/4, 1993. pp. 3-16. Alfonse T. Masi, "Review of the Epidemiology and Criteria of Fibromyalgia and Myofascial Pain Syndromes: Concepts of Illness in Populations as Applied to Dysfunctional Syndromes", Journal of Musculoskeletal Pain. vol. 1, No. 3/4, 1993, pp. 113-136. Israel A. Posner, "Treatment of Fibromyalgia Syndrome with Intravenous Lidocaine: A Prospective, Randomized Pilot Study", Journal of Musculoskeletal Pain. vol. 2(4). 1994, pp. 55-65. Robert M. Bennett, "Fibromyalgia Review", Journal of Musculoskeletal Pain. vol. 2(4). 1994, pp. 99-112. Russell I. Jon, "Foreword: NIH Conference on Fibromyalgia", Journal of Musculoskeletal Pain, vol. 2, No. 3, 1994 pp. xiii-xv. Muhammad B. Yunus, "Fibromyalgia Syndrome: Clinical Features and Spectrum", Journal of Musculoskeletal Pain. vol. 2, No. 3, 1994, pp. 5-21. Frederick Wolfe, "Fibromyalgia: On Criteria and Classification", Journal of Musculoskeletal Pain, vol. 2. No. 3. 1994, pp. 23-39. Frederick Wolfe, "Aspects of the Epidemiology of Fibromyalgia", Journal of Musculoskeletal Pain, vol. 2, No. 3, 1994, pp. 65-77. I. Jon Russell, "Biochemical Abnormalities in Fibromyalgia Syndrome", Journal of Musculoskeletal Pain, vol. 2, No. 3, 1994, pp. 101-115. R.J. Winn et al., "Individual and Combined Effects of Relaxin, Estrogen, and Progesterone in Ovariectomized Gilts. II. Effects on Mammary Development", Endocrinology, 1994, vol. 135, No. 3, pp. 1250-1255. Gillian D. Bryant-Greenwood et al., "Human RElaxins: Chemistry and Biology", Endocrine Reviews, vol. 15, No. 1, pp. 5-26, 1994. MR Johnson et al., "Relationship Between Ovarian Steroids, Gonadotrophins and Relaxin During the Menstrual Cycle", Acta Endocrinologica 1993, vol. 129, pp. 121-125. KJ Berkley et al., "Muscle Pain Thresholds in Dysmenorrheic Versus Normal Women: Variations as a Function of Segmental Site and Monthly Cycle", Abstract from the 3rd Wrold Congress on Myofascial Pain & Fibromyalgia San Antonio, Tx. Jul. 30-Aug. 3, 1995. Masi, Alfonse T., "Review of the Epidemiology and Criteria of Fibromyalgia and Myofascial Pain Syndromes: Concepts of Illness on Populations as Applied to Dysfunctional Syndromes," Journal of Musculoskeletal Pain, vol. 1, No. 3/4, 1993, pp. 113-136. |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A method for remodelling collagen fibers, comprising applying topically to the epidermis of the skin a composition comprising effective amounts of relaxin hormone in an emollient vehicle in a program of maintenance therapy, whereby the skin substantially regains and maintains its firmness, turgor, and elasticity during said therapy, said composition and amounts of human relaxin hormone, being selected to provide a therapeutically effective dose of relaxin hormone. 2. The method of claim 1 wherein the skin is human facial skin. 3. The method of claim 1 wherein the skin is mammary gland skin. |
| PATENT DESCRIPTION |
BACKGROUND OF THE INVENTION The present invention relates to the treatment of involuntary muscle dysfunctions. In particular, the present invention relates to the treatment of involuntary muscle dysfunction with relaxin hormone. Involuntary muscle dysfunction plagues a large portion of the chronic pain and chronic fatigue patient population. Two prominent conditions involving involuntary muscle dysfunction include fibromyalgia and myofascial pain syndrome, amongst others. Fibromyalgia is identified by the main symptoms of generalized chronic pain occurring mainly in the muscles and hyperalgesia, i.e. multiple tender points spread out over the body. The full range of symptoms include generalized pain, hyperalgesia, sleep disturbance, fatigue, muscle stiffness, hypersthesias, tension-type headaches, decreased muscle endurance and muscle weakness. Fibromyaglia has also been associated with irritable bowel syndrome, chronic fatigue syndrome, temporomandibular dysfunction syndrome, migraines, primary dysmenhorrea (painful menstruation) and others conditions including Raynaud's phenomenon. See Yunnus, Fibromyalgia Syndrome: Clinical Features and Spectrum, The Fibromyalgic Syndrome: Current Research and Future Directions in Epidemiology, Pathogenesis, and Treatment, 1994, pp. 5-21. See also Wolfe, When to Diagnose Fibromyalgia, Rheumatic Disease Clinics Of North America, Vol. 20, Number 2, May 1994. See Henriksson, Pathogenesis of Fibromyalgia, Journal of Musculoskeletal Pain, 1993, Vol. 1, pp. 3-16. Fibromyalgia is the second or third most common disorder seen in community practice. The economic effects of fibromyalgia are substantial. In one study, it was reported that only 60% of fibromyalgia patients were employed, 30% of patients changed jobs because of fibromyalgia, 10% of patients considered themselves disabled, and 6% received disability payments. See Rothschild et al, Retrospective Assessment of Fibromyalgia Therapeusis, Comprehensive Therapy 1994, Vol. 20, pp 545-549. Fibromyalgia also appears to be concentrated amongst the female patient population. It is estimated that about 80 to 90% of fibromyalgia patients are women. In addition, most patients are reported to fall in the 40 to 50 year age range. However, some studies have identified an archetypical patient as being a young women between the ages of 20 and 40. See Masi, A., Review of The Epidemiology and Criteria of Fibromyalgia and Myofascial Pain Syndromes: Concepts of Illness in Populations as Applied to Dysfunctional Syndromes, Journal of Musculoskeletal Pain, 1993, Vol. 1, pp. 113-116. See also Yunnus, supra, page 6. While there is no current cure for fibromyalgia, it has been reported that some patients have responded to therapy with Halcion.RTM. and hypnosis. See Rothschild et al. However, these treatment modalities primarily address sleep disturbance and do not squarely address the cause of fibromyalgia or its full range of symptoms. Moreover, the use of Halcion.RTM. is not suitable for long-term treatment. While Halcion.RTM. induces sleep, Halcion also inhibits the patient's ability to achieve rapid eye movement (REM) sleep, which is necessary for therapeutic sleep. Other conventional treatments of fibromyalgia include treating localized pain and muscle tension with intramuscular application of botulinum toxin as well as treatments including relaxation medication, exercise, and physical therapy. These latter treatment methods are aimed at relaxing and elongating the affected muscles. However, none of these previous attempts at alleviating the symptoms of fibromyalgia and related involuntary muscle dysfunctions are effective. Moreover, these methods do not address the cause of fibromyalgia and other involuntary muscle dysfunctions. In addition, many patients suffer from one or several of the symptoms (e.g., dysmenorrhea) associated with fibromyalgia without actually having fibromyalgia or the full range of symptoms. No single treatment is currently available for treating most or all of these symptoms. SUMMARY OF THE INVENTION The present invention is based on the recognition that the involuntary muscle dysfunctions associated with fibromyalgia, myofascial pain syndrome, dystonia, chronic fatigue syndrome, and other condition is the result of a deficiency of relaxin hormone or a suppression of relaxin's effect in the bloodstream. This lack of relaxin in the blood stream may be congenital or the result of another mechanism which suppresses the normal production or action of relaxin. Accordingly, a method of the present invention of treating involuntary muscle dysfunction comprises administering to a patient exhibiting symptoms associated with these conditions a therapeutically effective amount of relaxin hormone. The relaxin hormone will alleviate these conditions since relaxin acts to effect collagen formation and remodelling, thereby causing tissue changes of the type associated with parturition, i.e., smooth muscle relaxation, elongation of tendons and ligaments, etc. This recognition is based on clinical observations by the inventor of the symptoms reported by female patients with fibromyalgia or myofascial pain syndrome when these patients are pregnant or in menopause. In particular, the basic observation is that fibromyalgia patients and myofascial pain syndrome patients do not report or exhibit the same symptoms (generalized pain, fatigue, inflexibility) when they are pregnant that they report or exhibit when they are not pregnant. In short, many or all of the symptoms associated with these conditions (e.g., fibromyolgia, myofascial pain, etc.) disappear when these patients are pregnant. Specifically, a large number of fibromyalgia patients (and patients with other involuntary muscle dysfunction maladies) report that their pain-related symptoms subside during pregnancy and return after pregnancy. This relationship is significant since the vast majority of fibromyalgia patients are women. The disappearance of fibromyalgia symptoms in these patients when pregnant is explained by the relatively high elevation of relaxin during pregnancy. This recognition of relaxin as the primary causal agent in involuntary muscle dysfunction is confirmed by clinical observations by the inventor of patients with premenstrual pain syndrome (PMS). Women that have fibromyalgia or myofascial pain syndrome frequently have dysmenorrhea, reporting that their symptoms are aggravated just before and during the menstrual period. It is known in the art that the level of relaxin typically rises in women about 7-10 days after the midcycle surge of the luteinizing hormone and when conception does not occur, the level falls precipitously about one week before the menstrual period begins. The inventor has observed that female patients with PMS, fibromyaglia or myfascial pain syndrome with dysmenorrhea, all report an increase or beginning of their painful symptoms and muscle tension and discomfort one week before and during the menstrual period. Specifically, the inventor has observed that the precipitously falling level of the circulating relaxin corresponds to the beginning or increase in the level of patients' pain and discomfort one week before and during the menstrual period. Administering relaxin to patients with fibromyalgia, myofascial pain syndrome and related involuntary muscle dysfunctions is expected to significantly alleviate the core symptoms of these conditions, e.g., generalized pain and tenderness, as well as alleviate specific secondary symptoms such as dysmenorrhea. |
| PATENT EXAMPLES | This data is not available for free |
| PATENT PHOTOCOPY | Available on request |
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