WO1994015629A1 - Procede de traitement du syndrome de costen - Google Patents
Procede de traitement du syndrome de costen Download PDFInfo
- Publication number
- WO1994015629A1 WO1994015629A1 PCT/US1994/000626 US9400626W WO9415629A1 WO 1994015629 A1 WO1994015629 A1 WO 1994015629A1 US 9400626 W US9400626 W US 9400626W WO 9415629 A1 WO9415629 A1 WO 9415629A1
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- WO
- WIPO (PCT)
- Prior art keywords
- muscle
- pain
- agent
- patient
- syndrome
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the invention relates to a method for treating the symptoms of myofascial pain syndrome by specific partial, reversible chemical denervation of the myofascial pain source.
- Myofascial pain syndrome is a chronic pain condition with often widespread pain complaints, trigger points and tender points.
- Trigger points in particular are characteristic of the syndrome.
- a trigger point is an area which, when pressed by a pressure gauge or finger, produces pain in a distribution in which the symptoms appear to occur.
- Tender points are areas of the muscle that, when pressed, create pain at the site of compression. Tender points differ from trigger points in that pressure on a tender point does not reproduce or "trigger" the distribution of pain associated with the original complaint.
- Muscles afflicted with myofascial pain often demonstrate tender tight bands upon palpation. The pain is usually localized to the muscular area and is not associated with tenderness over bone articulation or anatomic areas occupied by tendon structures.
- Myofascial syndrome sometimes is misdiagnosed as fibromyalgia or fibrositis syndrome. These terms in older literature may have been interchangeable with chronic muscular pain; therefore, myofascial pain sometimes can be viewed as localized fibromyalgia.
- Fibromyalgia is a generalized syndrome characterized by tenderness within diffuse distribution of muscle groups and associated systemic complaints such as sleep disturbances, generalized fatigue, chronic headaches and irritable bowel symptoms. These characteristics distinguish it from myofascial pain syndrome.
- Localized fibromyalgia also has been referred to as "fibrositis", which may be considered almost the same as fibromyalgia.
- a palpable trigger point is essential to the diagnosis of myofascial pain syndrome.
- Pain referred from the trigger point is usually described as a subcutaneous location with slightly blurred edges; 2.
- Several muscles including the deltoid, gluteus maximus, oseratus posterior/inferior) refer pain locally in the immediate vicinity of the trigger point;
- Trigger points in the limb muscles refer pain distally rather than proximally;
- Pain occurring in certain muscles is referred into adjacent joints, occasionally mimicking arthritis
- Aching pain in the pltysma muscle secondary to myofascial causes is described as a "prickling" sensation
- Trigger points may refer hypesthesia (numbness) or anesthesia instead of pain.
- Myofascial pain syndrome often is associated with reduced range of motion. The pain complaint can be reproduced by digital pressure or by needle penetration of the trigger point. Pain is thought to be caused by unusual tension, tone and afferent receptors within muscle which carry the impulse perception of pain. These pain receptors have been termed “nociceptors. " Nociceptors are microanatomic elements within muscle which sense stretch and perhaps pain. Myofascial pain syndrome can be a cause of post ⁇ operative pain. For example, myofascial pain syndrome may arise after temporomandibular joint surgery or acoustic neuroma surgery.
- Myofascial pain is specifically distinguishable from pain arising from joint and bone by the absence of arthritis or other forms of joint pathology, as demonstrated on routine radiographs, computerized tomography (CT) or magnetic resonance imaging (MRI).
- CT computerized tomography
- MRI magnetic resonance imaging
- the trigger points in myofascial pain are clearly within the palpable body of the muscle. Tight bands are palpable in muscles demonstrating this particular syndrome, which often are associated with trigger points. Electrophysiologic measurement of changes at the trigger points have been attempted, but the results have not been consistent. Durett et al.. Am J Phys Med Rehabil, 70(3) :154-156 (1991); Fricton et al. , Arch Phys Med Rehabil, 66(5) ;314-317 (1985)
- the following represents a summary of clinical criteria for diagnosing myofascial pain syndrome caused by active trigger points.
- the five major criteria include:
- the history of therapy for myofascial syndrome has included the use of oral analgesics such as aspirin and acetominophen, the use of non-steroidal anti- inflammatory systemic drugs such as ibuprofen, injection of a local anesthetic such as LidocaineTM , physical therapy, biofeedback, and use of sensory stimulating devices such as acupuncture or TENS units for blocking sensory pain and reducing immobilization.
- oral analgesics such as aspirin and acetominophen
- non-steroidal anti- inflammatory systemic drugs such as ibuprofen
- injection of a local anesthetic such as LidocaineTM
- physical therapy such as a local anesthetic
- biofeedback a local anesthetic
- sensory stimulating devices such as acupuncture or TENS units for blocking sensory pain and reducing immobilization.
- the present invention relates to a method for alleviating pain and other symptoms associated with myofascial pain syndrome.
- the method comprises administering locally to a muscle of the patient affected by the syndrome an amount of a chemodenervating agent sufficient to alleviate the symptoms of the syndrome, wherein the chemodenervating agent deactivates impulse transmission at the neural motor endplates in the muscle.
- the present method provides localized relief from myofascial pain which is sustained over a period of time.
- the invention in another aspect, relates to producing an analgesic effect in a patient experiencing myofascial pain by administering locally to a muscle of the patient an analgesically effective amount of the chemodenervating agent.
- the analgesic effect so produced is sustained for a prolonged period of time, e.g., for at least 7 days, generally for between 2 and 12 weeks, and up to as long as about 16 weeks.
- Chemodenervating agents useful in the present invention are agents which specifically block release of acetylcholine from the neural motor end plates of the treated muscle.
- Botulinum-derived toxins are preferred agents for this purpose.
- Botulinum toxins block release of acetylcholine from neural motor endplates, resulting in induction of muscle fiber atrophy and muscle weakness, while retaining muscle function.
- Botulinum toxin affects the axonal terminal of motor nerves without having any known effect on the sensory nervous system.
- collateral axonal sprouting accour, and new neuromuscular junctions are established in the muscle, generally over a 10 to 12 week period.
- the effects of botulinum toxin are temporary and generally run a course of about 12 weeks. After the twelve week period, normal innervation returns to the muscle and there is regeneration of muscle fiber size. Another round of treatment can be administered at this time, if necessary or desirable.
- a therapeutic amount of a botulinum toxin preparation is administered locally to a muscle of a patient suffering from myofascial pain syndrome.
- the toxin preparation is injected directly into the muscle or muscles affected by the syndrome.
- a dose in the range of from about 5 to about 1000 IU of botulinum-derived toxin generally is effective for this purpose.
- the present method provides a therapy which confers localized, sustained relief from myofascial pain over a period of several weeks or months.
- the method has several advantages over traditional treatments for myofascial pain. For example, it avoids the need for surgery or other invasive procedures, which carry considerable risk, and avoids the use of systemic drugs, which may have undesirable side effects.
- Chemodenervating pharmaceuticals such as botulinum toxin
- central nervous system functions such as cognitive reasoning, sleep patterns, appetite, affective disposition or other central nervous system functions.
- the present invention is distinctly different from all prior therapies in that blockage of neuromuscular transmission is the only effect of the toxin without sensory and neural effects. Reduction in tone, resting tension, and contractility in the muscle creates a secondary effect at the nociceptors resulting in decreased afferent "pain" output to the central nervous system.
- the present method provides a therapeutic treatment for alleviating pain having a myofascial origin by chemically inducing denervation of a muscle or muscles.
- myofascial refers to a sheet of fibrous tissue (the "fascia") which encloses muscles or groups of muscles and separates muscular layers or groups.
- Myofascial pain syndrome is a well-defined syndrome having a characteristic set of symptoms, as set out in detail hereinabove.
- the term “myofascial pain syndrome” may include disorders diagnosed as localized fibromyalgia or localized fibrositis. The term is intended to include any disorders which meet the diagnostic criteria characteristic of myofascial pain syndrome.
- the present method involves administering to a muscle of a patient afflicted with myofascial pain syndrome an amount of a chemical denervating agent which specifically denervates the neural motor endplates in the muscle sufficient to alleviate the pain symptoms.
- the present method produces a localized, sustained analgesic effect in a patient experiencing myofascial pain by administering locally to the afflicted muscle or muscles an analgesically effective amount of a chemical denervating agent sufficient to denervate neural motor endplates of the afflicted muscle.
- Chemical denervating agents which are effective for this purpose are agents which specifically denervate neural motor endplates of the affected muscles, for example, by blocking the release of acetylcholine from the endplates.
- the chemical denervating agent induces a number of changes in the muscle, including diffuse muscular atrophy, elongation of muscle fiber units and a decrease in the output of afferent impulses from the treated muscle. Injection of the denervating agent causes the treated muscle to loosen and elongate and decreases its resting tone, thereby increasing the amount of passive stretch in the muscle. Without wishing to be bound by theory, it is believed that decreasing the resting tone within muscle by chemodenervation reduces the afferent impulses transmitted to the central nervous system.
- the chemical denervating agent loosens muscle tone and contractility which in turn influences nociceptors in the affected muscles, thereby blocking transmission of the pain impulses.
- the effects of the denervating agent are sustained for a period of time which can be influenced by several factors, including the amount of the agent administered, it's extent of diffusion in the muscle, the amount and type of diluent and the patient's individual reaction to the agent. The effect in most patients will last for at least 7 days, and typically up to about 12 weeks, thus affording prolonged pain relief.
- Botulinum toxins are a family of toxins derived from Clostridium botulinum. There are seven known serotypes of botulinum toxins, designated types A through G. Pharmaceutical grade type A toxin is commercially available from Allergan Pharmaceuticals, Inc. under the tradename Oculinum . However, the method of the invention can be practiced using any physiologically acceptable injectable substance which interrupts neuromuscular transmission at the neuromuscular junction.
- the chemodenervating agents of this invention can be processed in accordance with conventional methods of pharmacy to produce medicinal agents for administration to patients, e.g., humans.
- the agents typically are employed in admixture with conventional excipients and/or diluents, i.e., pharmaceutically acceptable carrier substances suitable for injection which do not deleteriously affect the active agent.
- suitable carriers include, but are not limited to, water, salt solutions, and physiologic buffers. For parenteral application, injectable sterile solutions are preferred.
- the agent can be administered by any method suitable for locally administering a drug, including, for example, transdermal diffusion, transcutaneous injection, intramuscular injection or implantation of a device which releases the substance into the desired area.
- Transcutaneous injection directly into the afflicted muscle is the preferred method.
- a botulinum toxin preparation is injected into a muscle of a patient afflicted with myofascial pain syndrome. Injection of a botulinum toxin preparation into the muscle deposits a bolus of the material at the injection point which diffuses outwardly. The distance of diffusion is not clearly understood and seems to depend upon a number of factors, including the nature and amount of diluent, the mass of the toxin molecule, the population of presynaptic receptors about the site of the injection and the physiological condition of the patient.
- the therapeutic and analgesic effects are achieved at dosage levels in the range of about 5 international units (IU) to about 1000 IU of the chemodenervating agent.
- a preferred dosage for this purpose is less than 500 IU, and most preferably about 300 IU or less.
- the dosage preferably is administered as a plurality of injections about the trigger point in the afflicted muscle or muscle group.
- An international unit is defined as the LD 5Q for a standard 20 gram white mouse. Dosages also can be administered based upon the volume of muscle denervated by a unit quantity of a chemodenervating agent as described in above-referenced patent application USSN 07/570,395.
- active compound in a specific case will vary according to the agent utilized, the particular compositions formulated and the particular site and patient being treated. Dosages for a given patient can be determined using customary, clinical practices. Botulinum toxin preparations have been used in the past to treat certain spasmodic conditions of muscle. However, these preparations have not been indicated for the management of specific pain syndromes. The present invention demonstrates that chemodenervating agents such as botulinum toxins can be applied for the localized, sustained relief of pain resulting from myofascial pain syndrome.
- the present method can be used to treat any muscle or muscle group in a patient afflicted with myofascial pain syndrome.
- Anatomic regions in which myofascial pain syndrome has been described include, but are not limited to, the following muscles with associated restrictions in range of motion and/or referred pain:
- Lateral pterygoid Refers pain to ears, temporomandibular joint, cheek and jaw
- Medial pterygoid Refers pain to ears and temporomandibular joint, cheek, jaw, throat and front of neck
- Multifidi Refers pain to back of neck Occipitalis Refers pain to back of head and eye area
- Orbicularis oculi Refers pain to eye area, cheek and jaw
- Temporalis Refers pain to back of head, temporal area, eye area and teeth
- Zygomaticus major Refers pain to front of head, cheek and jaw
- the present method can be used to treat post operative myofascial pain.
- Myofascial pain syndrome is a principal component of post operative complaints.
- Traditional treatments for post-operative pain include physical therapy and non-steroidal anti-inflammatory medications, which have met with varying degrees of success.
- the present method is effective in post ⁇ operative relieving myofascial pain syndrome and has the advantage of providing localized refief to the pain source without administering systemic drugs which may induce unwanted side effects.
- An example of the efficacy of the present method in treating post ⁇ operative myofascial pain is shown in Example 2.
- E.C. is an otherwise healthy 26 year old woman with a history of chronic pain.
- the pain has been characterized as a dull ache primarily within the region of the left shoulder that has been radiating up the posterior aspect of her skull and down towards the mid position of the low back.
- the pain has been very severe and has prevented the patient from maintaining gainful employment for approximately two years. She has undergone extensive evaluation at the Pain Clinic at the University of Massachusetts Hospital, Massachusetts General Hospital and Spaulding Rehabilitation Hospital.
- the pain was characterized as radiating to the inner aspect of her arm as well as to the region of the left portion of her neck. Although there was no posture abnormality associated with the pain, the patient felt stiffness in her neck movement when trying to make rotation excursions to the right and left. There was no evidence of dystonia or involuntary movement present.
- Tense bands were palpated within her left trapezius muscle in a region of a consistent trigger point. Some generalized increase in muscle tone was also noted in this region. Pressing on the trigger point produced pain in the same region which the pain was spontaneously present. Pressing on the trigger point also produced pain in the same quality as that experienced by the patient. Extensive neuroradiographic work-up of the cervical spine, cervical dorsal and lumbar spine failed to show any substantial bone or joint pathology.
- botulinum A toxin Allergan Pharmaceuticals, Inc.
- the patient underwent a second injection receiving a 5 point injection of botulinum toxin at a total dose of 100 IU over the left trapezius muscle.
- the patient was able to increase her activity to part-time employment and increase her demands of physical therapy.
- Her physical therapist noticed a clear improvement in her ability to function and noted that there had been clear progress after the injections.
- the patient noticed increased strength in her muscles and experienced less headache pain.
- LF LF is an unfortunate 36 year old woman with a 15 year history of temporomandibular joint disease and chronic pain along the masseter and temporalis muscles. Fifteen years prior to evaluation she noted increased immobility of the jaw associated with pain and jaw opening and closing and tenderness along each side of the face. The left side was originally thought to be worse than the right. She was diagnosed as having temporomandibular joint (TMJ) dysfunction with subluxation of the joint and was treated with surgical orthoplasty meniscusectomy and condyle resection.
- TMJ temporomandibular joint
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- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
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- Neurology (AREA)
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- Pain & Pain Management (AREA)
- Gastroenterology & Hepatology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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Abstract
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP94906673A EP0679090A1 (fr) | 1993-01-15 | 1994-01-13 | Procede de traitement du syndrome de costen |
JP51636094A JP4381477B2 (ja) | 1993-01-15 | 1994-01-13 | 筋膜疼痛症候群の治療方法 |
AU60304/94A AU6030494A (en) | 1993-01-15 | 1994-01-13 | Method for treating myofascial pain syndrome |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US005,040 | 1979-01-22 | ||
US504093A | 1993-01-15 | 1993-01-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994015629A1 true WO1994015629A1 (fr) | 1994-07-21 |
Family
ID=21713832
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1994/000626 WO1994015629A1 (fr) | 1993-01-15 | 1994-01-13 | Procede de traitement du syndrome de costen |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0679090A1 (fr) |
JP (1) | JP4381477B2 (fr) |
AU (1) | AU6030494A (fr) |
CA (1) | CA2153781A1 (fr) |
WO (1) | WO1994015629A1 (fr) |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995028171A1 (fr) * | 1994-04-15 | 1995-10-26 | Mount Sinai School Of Medicine Of The City University Of New York | Traitement de la dystonie neurovegetative avec du botulinum |
WO1996033273A1 (fr) * | 1995-04-21 | 1996-10-24 | The Speywood Laboratory Limited | Derives de la toxine botulinique capables de modifier les fonctions des afferents peripheriques |
EP0758900A1 (fr) * | 1994-05-09 | 1997-02-26 | BINDER, William J. | Procede de reduction des maux de tete |
EP0770395A1 (fr) * | 1993-12-28 | 1997-05-02 | Allergan | L'utilisation de la toxine de botulinum pour soulager les maux de tête |
WO1997034624A1 (fr) * | 1996-03-20 | 1997-09-25 | Allergan Sales, Inc. | Traitement injectable destine a maitriser les spasmes musculaires et la douleur liee a des spasmes musculaires |
US6113915A (en) * | 1999-10-12 | 2000-09-05 | Allergan Sales, Inc. | Methods for treating pain |
US6306423B1 (en) | 2000-06-02 | 2001-10-23 | Allergan Sales, Inc. | Neurotoxin implant |
US6423319B1 (en) | 2000-10-04 | 2002-07-23 | Allergan Sales, Inc. | Methods for treating muscle injuries |
US6464986B1 (en) | 2000-04-14 | 2002-10-15 | Allegan Sales, Inc. | Method for treating pain by peripheral administration of a neurotoxin |
US6565870B1 (en) | 2000-04-28 | 2003-05-20 | Allergan, Inc. | Methods for treating bone tumors |
US6623742B2 (en) | 2001-09-17 | 2003-09-23 | Allergan, Inc. | Methods for treating fibromyalgia |
US7255866B2 (en) | 2001-09-17 | 2007-08-14 | Allergan, Inc. | Botulinum toxin therapy for fibromyalgia |
US7255865B2 (en) | 2000-12-05 | 2007-08-14 | Allergan, Inc. | Methods of administering botulinum toxin |
US7378389B2 (en) | 1991-09-24 | 2008-05-27 | Allergan, Inc. | Botulinum toxin neurotoxic component for treating juvenile cerebral palsy |
US7479281B1 (en) | 2000-12-05 | 2009-01-20 | Allergan, Inc. | Botulinum toxin for treating postherpetic neuralgia |
US7491799B2 (en) | 2000-07-21 | 2009-02-17 | Allergan, Inc. | Modified botulinum neurotoxins |
US7501130B2 (en) | 1993-12-28 | 2009-03-10 | Allergan, Inc. | Methods for treating myofascial pain |
US7534863B2 (en) | 2000-07-21 | 2009-05-19 | Allergan, Inc. | Leucine-based motifs and enhanced biological persistence of clostridial neurotoxins |
US7691983B2 (en) | 2000-07-21 | 2010-04-06 | Allergan, Inc. | Chimera botulinum toxin type E |
US8187612B2 (en) | 1993-12-28 | 2012-05-29 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating a spastic muscle |
US8557256B2 (en) | 1993-12-28 | 2013-10-15 | Allergan, Inc. | Treatment for cervical dystonia with the neurotoxic component of a botulinum toxin |
US10441641B2 (en) | 2005-06-14 | 2019-10-15 | Revance Therapeutics, Inc. | Botulinum toxin and the treatment of primary disorders of mood and affect |
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1994
- 1994-01-13 JP JP51636094A patent/JP4381477B2/ja not_active Expired - Fee Related
- 1994-01-13 WO PCT/US1994/000626 patent/WO1994015629A1/fr not_active Application Discontinuation
- 1994-01-13 EP EP94906673A patent/EP0679090A1/fr not_active Withdrawn
- 1994-01-13 CA CA002153781A patent/CA2153781A1/fr not_active Abandoned
- 1994-01-13 AU AU60304/94A patent/AU6030494A/en not_active Abandoned
Patent Citations (3)
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US5053005A (en) * | 1989-04-21 | 1991-10-01 | Gary E. Borodic | Chemomodulation of curvature of the juvenile spine |
US5183462A (en) * | 1990-08-21 | 1993-02-02 | Associated Synapse Biologics | Controlled administration of chemodenervating pharmaceuticals |
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Cited By (65)
Publication number | Priority date | Publication date | Assignee | Title |
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US7378389B2 (en) | 1991-09-24 | 2008-05-27 | Allergan, Inc. | Botulinum toxin neurotoxic component for treating juvenile cerebral palsy |
US7501130B2 (en) | 1993-12-28 | 2009-03-10 | Allergan, Inc. | Methods for treating myofascial pain |
EP1366770A2 (fr) * | 1993-12-28 | 2003-12-03 | Allergan, Inc. | Utilisation de la toxine botulinique pour le traitement de la douleur liée à des troubles musculaires |
EP0770395A1 (fr) * | 1993-12-28 | 1997-05-02 | Allergan | L'utilisation de la toxine de botulinum pour soulager les maux de tête |
JP2010202659A (ja) * | 1993-12-28 | 2010-09-16 | Allergan Inc | 筋肉に関連する痛みを処置するためのボツリヌス毒素の神経毒成分 |
EP1757325A1 (fr) * | 1993-12-28 | 2007-02-28 | Allergan, Inc. | Utilisation de la toxine botulinique pour traiter les douleurs myofasciales |
EP1366770A3 (fr) * | 1993-12-28 | 2004-03-17 | Allergan, Inc. | Utilisation de la toxine botulinique pour le traitement de la douleur liée à des troubles musculaires |
US8052980B2 (en) | 1993-12-28 | 2011-11-08 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating arthritis |
EP1502600A1 (fr) * | 1993-12-28 | 2005-02-02 | Allergan, Inc. | Utilisation de la toxine botulinique pour le traitement de maladies liées aux muscles lisses |
EP1103267A1 (fr) * | 1993-12-28 | 2001-05-30 | Allergan Sales, Inc. | Toxines botulinum utilisées dans le traitement de divers troubles, et douleurs associées |
US8557256B2 (en) | 1993-12-28 | 2013-10-15 | Allergan, Inc. | Treatment for cervical dystonia with the neurotoxic component of a botulinum toxin |
US8187612B2 (en) | 1993-12-28 | 2012-05-29 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating a spastic muscle |
EP1486214A1 (fr) * | 1993-12-28 | 2004-12-15 | Allergan, Inc. | Toxine botulinique pour le traitement des spasmes musculaires |
WO1995028171A1 (fr) * | 1994-04-15 | 1995-10-26 | Mount Sinai School Of Medicine Of The City University Of New York | Traitement de la dystonie neurovegetative avec du botulinum |
EP0758900A4 (fr) * | 1994-05-09 | 1997-05-21 | William J Binder | Procede de reduction des maux de tete |
EP1086702A3 (fr) * | 1994-05-09 | 2001-04-04 | BINDER, William J. | Toxines de botulinum pour le traitement des cephalées de la migraine |
EP1086702A2 (fr) * | 1994-05-09 | 2001-03-28 | BINDER, William J. | Toxines de botulinum pour le traitement des cephalées de la migraine |
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Also Published As
Publication number | Publication date |
---|---|
AU6030494A (en) | 1994-08-15 |
CA2153781A1 (fr) | 1994-07-21 |
JPH08508241A (ja) | 1996-09-03 |
EP0679090A1 (fr) | 1995-11-02 |
JP4381477B2 (ja) | 2009-12-09 |
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