US20050112146A1 - Botulinum toxin neurotoxic components formulations - Google Patents
Botulinum toxin neurotoxic components formulations Download PDFInfo
- Publication number
- US20050112146A1 US20050112146A1 US10/976,507 US97650704A US2005112146A1 US 20050112146 A1 US20050112146 A1 US 20050112146A1 US 97650704 A US97650704 A US 97650704A US 2005112146 A1 US2005112146 A1 US 2005112146A1
- Authority
- US
- United States
- Prior art keywords
- botulinum toxin
- toxin type
- botulinum
- sterile
- toxin
- 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
Links
Classifications
-
- 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
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
- A61K38/4893—Botulinum neurotoxin (3.4.24.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/24—Metalloendopeptidases (3.4.24)
- C12Y304/24069—Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention relates to the treatment of cerebral palsy in a juvenile patient and in particular to the promotion of normal muscle growth in a juvenile patient suffering from dynamic contractures caused by cerebral palsy.
- Cerebral palsy is a collective name given to a range of conditions caused by brain injury caused at or around the time of birth, or in the first year of an infant's life.
- the brain injury may be caused, for example, by trauma during delivery. It may also arise through such causes as trauma due to road traffic accidents or meningitis during the first year of life. It has been found that there is an increased risk of cerebral palsy in prematurely born babies and, as a result of the improvements in technology which enable premature babies to be kept alive from a much earlier age, the incidence of cerebral palsy in many countries is actually increasing rather than falling.
- a bacterial toxin, botulinum toxin has been used in the treatment of a number of conditions involving muscular spasm, for example blepharospasm, spasmodic torticollis (cervical dystonia), oromandibular dystonia and spasmodic dysphonia (laryngeal dystonia).
- the toxin binds rapidly and strongly to presynaptic cholinergic nerve terminals and inhibits the exocytosis of acetylcholine by decreasing the frequency of acetyl choline release. This results in paralysis, and hence relaxation, of the muscle afflicted by spasm.
- the neurotoxic component of botulinum toxin has a molecular weight of about 150 kilodaltons and is thought to comprise a short polypeptide chain of about 50 kD which is considered to be responsible for the toxic properties of the toxin, and a larger polypeptide chain of about 100 kD which is believed to be necessary to enable the toxin to penetrate the nerve.
- the “short” and “long” chains are linked together by means of disulphide bridges.
- the neurotoxic polypeptide component is present in a complex with non-toxic proteins and haemagglutinins, the molecular weight of the complex being in the region of 900 kD.
- Botulinum toxin is obtained commercially by establishing and growing cultures of C. botulinum in a fermenter and then harvesting and purifying the fermented mixture in accordance with known techniques.
- botulinum toxin is currently available commercially from several sources, for example from Porton Products Ltd UK under the tradename “DYSPORT”, and from Allergan Inc, Irvine, Calif. under the trade name “OCULINUM”.
- the present invention provides a method of treating a juvenile patient suffering from arrested muscle growth arising from the presence of dynamic contractures of the muscle, which method comprises administering to the patient a therapeutically effective amount of a substance which blocks the release of synaptic vesicles containing acetylcholine.
- the present invention also provides a method of treating a juvenile patient suffering from cerebral palsy, which method comprises administering to the patient a therapeutically effective amount of a substance which blocks the release of synaptic vesicles containing acetylcholine.
- the invention provides a method of treating a juvenile patient suffering from arrested muscle growth arising from the presence of dynamic contractures of the muscle, which method comprises administering to the patient a therapeutically effective amount of a presynaptic neurotoxin, for example a bacterial neurotoxin such as botulinum toxin.
- a presynaptic neurotoxin for example a bacterial neurotoxin such as botulinum toxin.
- the invention provides a method of treating a juvenile patient suffering from arrested muscle growth due to cerebral palsy, which method comprises administering a presynaptic neurotoxin (for example a bacterial neurotoxin such as botulinum toxin) to the patient in a non toxic amount sufficient to reduce muscle tone and promote improved muscle growth.
- a presynaptic neurotoxin for example a bacterial neurotoxin such as botulinum toxin
- the botulinum toxin used according to the present invention preferably is Botulinum toxin A.
- Botulinum toxin A is available commercially from Porton Products Limited, UK, and from Allergan Inc, Irvine, Calif.
- Administration of the toxin preferably is by means of intramuscular injection directly into a spastic muscle, in the region of the neuromuscular junction, although alternative types of administration (e.g. sub-cutaneous injection) which can deliver the toxin directly to the affected muscle region may be employed where appropriate.
- the toxin can be presented as a sterile pyrogen-free aqueous solution or dispersion and as a sterile powder for reconstitution into a sterile solution or dispersion.
- tonicity adjusting agents such as sodium chloride, glycerol and various sugars can be added.
- Stabilisers such as human serum albumin may also be included.
- the formulation may be preserved by means of a suitable pharmaceutically acceptable preservative such as a paraben, although preferably it is unpreserved.
- the toxin is formulated in unit dosage form, for example it can be provided as a sterile solution in a vial, or as a vial or sachet containing a lyophilised powder for reconstituting a suitable carrier such as water for injection.
- the toxin e.g. botulinum toxin A is formulated in a solution containing saline and pasteurised human serum albumin, which stabilises the toxin.
- the solution is sterile filtered (0.2 micron filter), filled into individual vials and then vacuum dried to give a sterile lyophilised powder.
- the powder can be reconstituted by the addition of sterile unpreserved normal saline (sodium chloride 0.9% for injection).
- administration of the botulinum toxin should commence before the child has completed its growing period and fixed myostatic contracture has occurred.
- the benefits of the invention can be maximised by administering the botulinum toxin to the child at an early stage in its growing period, for example before the child reaches the age of six.
- the dose of toxin administered to the patient will depend upon the severity of the condition e.g. the number of muscle groups requiring treatment, the age and size of the patient and the potency of the toxin.
- the potency of the toxin is expressed as a multiple of the LD 50 value for the mouse, one “unit” of toxin being defined as being the equivalent amount of toxin that kills 50% of a group of mice.
- the definition of potency as used hereinafter is the definition currently used in relation to the product marketed by Porton Products Limited. According to this definition, the potency of the botulinum toxin A available from Porton Products Ltd is such that one nanogram contains 40 mouse units (units).
- the dose administered to the patient will be up to about 1000 units, for example up to about 500 units, and preferably in the range from about 80 to about 460 units per patient per treatment, although smaller or larger doses may be administered in appropriate circumstances.
- the potency of botulinum toxin, and its long duration of action, means that doses will tend to be administered on an infrequent basis.
- both the quantity of toxin administered, and the frequency of its administration will be at the discretion of the physician responsible for the treatment, and will be commensurate with questions of safety and the effects produced by the toxin.
- the criteria for inclusion in the study were the presence of dynamic contractures interfering with function, without clinical evidence of fixed myostatic contracture.
- the children entering the study were suffering from spastic tetraplegia, diplegia, hemiplegia or monoplegia.
- the hamstrings and/or calf muscles of each patient were injected with a sterile solution containing the botulinum toxin A (obtained from Porton Products Limited, UK). Total patient doses ranged from 80 units to 460 units (one unit being equivalent to the murine LD 50 ).
- the aim was given to the anatomy of the muscle group, the aim being to inject the area with the highest concentration of neuromuscular junctions.
- the position of the needle in the muscle was confirmed by putting the muscle through its range of motion and observing the resultant motion of the needle end.
- General anaesthesia, local anaesthesia and sedation were used according to the age of the patient, the number of sites to be injected and the particular needs of the patient.
- mice were sacrificed at maturity and the hind limbs dissected to allow measurement of the muscle and bones.
- the spastic mice had a 13% failure of longitudinal muscle growth compared with their normal siblings.
- the muscles of the spastic mice injected with Botulinum had growth identical to that of their normal siblings. There was no difference in growth between normal mice injected with saline or Botulinum.
- Botulinum toxin A has been illustrated by reference to Botulinum toxin A but it should be understood that the invention is not limited to the use of this toxin.
- Botulinum toxins may be employed.
- other presynapnatic neurotoxins e.g. of bacterial origin
- synthetic analogues of the botulinum toxins may be envisaged wherein the 50 kd chain and/or the 100 kd chain are subjected to amino acid insertions, deletions and/or substitutions and, provided that such analogues retain the general type of activity exhibited by Botulinum toxin A, their use in the manner described hereinbefore is embraced by the present invention.
- the invention is also considered to embrace the use of substances structurally dissimilar to Botulinum toxin A, provided that such substances possess a prolonged ability to inhibit or block release of the synaptic vesicles containing acetylcholine.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention provides for the use of a presynaptic neurotoxin (for example a bacterial neurotoxin such as botulinum toxin A) for the manufacture of a medicament for the treatment of cerebral palsy in juvenile patients. The juvenile patients are preferably juveniles of up to 6 years in age.
Description
- The present invention relates to the treatment of cerebral palsy in a juvenile patient and in particular to the promotion of normal muscle growth in a juvenile patient suffering from dynamic contractures caused by cerebral palsy.
- Cerebral palsy is a collective name given to a range of conditions caused by brain injury caused at or around the time of birth, or in the first year of an infant's life. The brain injury may be caused, for example, by trauma during delivery. It may also arise through such causes as trauma due to road traffic accidents or meningitis during the first year of life. It has been found that there is an increased risk of cerebral palsy in prematurely born babies and, as a result of the improvements in technology which enable premature babies to be kept alive from a much earlier age, the incidence of cerebral palsy in many countries is actually increasing rather than falling.
- Although the brain injury causing cerebral palsy is a non-progressive injury, its effects may change as the sufferer grows older. The largest group of sufferers from cerebral palsy suffer from spastic cerebral palsy. Spastic cerebral palsy is characterised by dynamic contractures of the muscles which impair or inhibit completely the sufferer's ability to use his or her muscles. Moreover, muscle growth is impaired such that the longitudinal muscles become shorter relative to their associated bones as the infant grows older. Where the leg muscles are affected, the mobility of the sufferer can be severely reduced. Conventional attempts to cure this defect and to restore a measure of normal mobility typically have involved surgical intervention to alter the lengths of the tendons once the stage has been reached at which the knee joint can no longer be straightened or the sufferer can only walk on tiptoe.
- There remains a need for a treatment which allows the longitudinal muscles to grow normally, thereby removing, or at least minimising the need to resort to surgical intervention. Moreover, there remains a need for a treatment which can augment surgical intervention to improve the mobility of the sufferer.
- A bacterial toxin, botulinum toxin, has been used in the treatment of a number of conditions involving muscular spasm, for example blepharospasm, spasmodic torticollis (cervical dystonia), oromandibular dystonia and spasmodic dysphonia (laryngeal dystonia). The toxin binds rapidly and strongly to presynaptic cholinergic nerve terminals and inhibits the exocytosis of acetylcholine by decreasing the frequency of acetyl choline release. This results in paralysis, and hence relaxation, of the muscle afflicted by spasm.
- The term Botulinum toxin as used herein is a generic term embracing the family of toxins produced by the anaerobic bacterium Clostridium botulinum and, to date, seven immunologically distinct toxins have been identified. These have been given the designations A, B, C, D, E, F and G. For further information concerning the properties of the various botulinum toxins, reference is made to the article by Jankovic & Brin, The New England Journal of Medicine, pp 1186-1194, No 17, 1991 and to the review by Charles L Hatheway, Chapter 1 of the book entitled Botulinum Neurotoxin and Tetanus Toxin Ed. L. L. Simpson, published by Academic Press Inc. of San Diego Calif. 1989, the disclosures in which are incorporated herein by reference.
- The neurotoxic component of botulinum toxin has a molecular weight of about 150 kilodaltons and is thought to comprise a short polypeptide chain of about 50 kD which is considered to be responsible for the toxic properties of the toxin, and a larger polypeptide chain of about 100 kD which is believed to be necessary to enable the toxin to penetrate the nerve. The “short” and “long” chains are linked together by means of disulphide bridges.
- The neurotoxic polypeptide component is present in a complex with non-toxic proteins and haemagglutinins, the molecular weight of the complex being in the region of 900 kD.
- Botulinum toxin is obtained commercially by establishing and growing cultures of C. botulinum in a fermenter and then harvesting and purifying the fermented mixture in accordance with known techniques.
- The “A” form of botulinum toxin is currently available commercially from several sources, for example from Porton Products Ltd UK under the tradename “DYSPORT”, and from Allergan Inc, Irvine, Calif. under the trade name “OCULINUM”.
- It has now been found by the present inventor that children suffering from cerebral palsy related dynamic muscle contractures exhibit improvements in function following treatment with botulinum toxin and that such functional improvements persist when the tone reducing effects of the toxin have worn off.
- It has also been found that by administering botulinum toxin to a juvenile spastic mammal during its growth phase, the consequent reduction in tone of the spastic muscle enables increased longitudinal growth of the muscle to take place.
- In a first aspect, the present invention provides a method of treating a juvenile patient suffering from arrested muscle growth arising from the presence of dynamic contractures of the muscle, which method comprises administering to the patient a therapeutically effective amount of a substance which blocks the release of synaptic vesicles containing acetylcholine.
- The present invention also provides a method of treating a juvenile patient suffering from cerebral palsy, which method comprises administering to the patient a therapeutically effective amount of a substance which blocks the release of synaptic vesicles containing acetylcholine.
- In a further aspect the invention provides a method of treating a juvenile patient suffering from arrested muscle growth arising from the presence of dynamic contractures of the muscle, which method comprises administering to the patient a therapeutically effective amount of a presynaptic neurotoxin, for example a bacterial neurotoxin such as botulinum toxin.
- In a still further aspect the invention provides a method of treating a juvenile patient suffering from arrested muscle growth due to cerebral palsy, which method comprises administering a presynaptic neurotoxin (for example a bacterial neurotoxin such as botulinum toxin) to the patient in a non toxic amount sufficient to reduce muscle tone and promote improved muscle growth.
- The botulinum toxin used according to the present invention preferably is Botulinum toxin A. Botulinum toxin A is available commercially from Porton Products Limited, UK, and from Allergan Inc, Irvine, Calif.
- Administration of the toxin preferably is by means of intramuscular injection directly into a spastic muscle, in the region of the neuromuscular junction, although alternative types of administration (e.g. sub-cutaneous injection) which can deliver the toxin directly to the affected muscle region may be employed where appropriate. The toxin can be presented as a sterile pyrogen-free aqueous solution or dispersion and as a sterile powder for reconstitution into a sterile solution or dispersion.
- Where desired, tonicity adjusting agents such as sodium chloride, glycerol and various sugars can be added. Stabilisers such as human serum albumin may also be included. The formulation may be preserved by means of a suitable pharmaceutically acceptable preservative such as a paraben, although preferably it is unpreserved.
- It is preferred that the toxin is formulated in unit dosage form, for example it can be provided as a sterile solution in a vial, or as a vial or sachet containing a lyophilised powder for reconstituting a suitable carrier such as water for injection.
- In one embodiment the toxin, e.g. botulinum toxin A is formulated in a solution containing saline and pasteurised human serum albumin, which stabilises the toxin. The solution is sterile filtered (0.2 micron filter), filled into individual vials and then vacuum dried to give a sterile lyophilised powder. In use, the powder can be reconstituted by the addition of sterile unpreserved normal saline (sodium chloride 0.9% for injection).
- In order for the benefits of the invention to be realised, administration of the botulinum toxin should commence before the child has completed its growing period and fixed myostatic contracture has occurred. The benefits of the invention can be maximised by administering the botulinum toxin to the child at an early stage in its growing period, for example before the child reaches the age of six.
- The dose of toxin administered to the patient will depend upon the severity of the condition e.g. the number of muscle groups requiring treatment, the age and size of the patient and the potency of the toxin. The potency of the toxin is expressed as a multiple of the LD50 value for the mouse, one “unit” of toxin being defined as being the equivalent amount of toxin that kills 50% of a group of mice. The definition of potency as used hereinafter is the definition currently used in relation to the product marketed by Porton Products Limited. According to this definition, the potency of the botulinum toxin A available from Porton Products Ltd is such that one nanogram contains 40 mouse units (units).
- Typically, the dose administered to the patient will be up to about 1000 units, for example up to about 500 units, and preferably in the range from about 80 to about 460 units per patient per treatment, although smaller or larger doses may be administered in appropriate circumstances. The potency of botulinum toxin, and its long duration of action, means that doses will tend to be administered on an infrequent basis. Ultimately, however, both the quantity of toxin administered, and the frequency of its administration will be at the discretion of the physician responsible for the treatment, and will be commensurate with questions of safety and the effects produced by the toxin.
- The invention will now be illustrated in greater detail by reference to the following non-limiting examples which describe the results of clinical studies with botulinum toxin A:
- Thirty three children suffering from cerebral palsy, having a mean age of seven years and an age range of two to seventeen years, were selected for participation in a clinical study.
- The criteria for inclusion in the study were the presence of dynamic contractures interfering with function, without clinical evidence of fixed myostatic contracture. Before entering the study, all children underwent clinical evaluation, physiotherapist's assessment and parental assessment. All ambulatory patients underwent gait analysis using electrogoniometers. The children entering the study were suffering from spastic tetraplegia, diplegia, hemiplegia or monoplegia.
- The hamstrings and/or calf muscles of each patient were injected with a sterile solution containing the botulinum toxin A (obtained from Porton Products Limited, UK). Total patient doses ranged from 80 units to 460 units (one unit being equivalent to the murine LD50). Before injecting any muscle group, careful consideration was given to the anatomy of the muscle group, the aim being to inject the area with the highest concentration of neuromuscular junctions. Before injecting the muscle, the position of the needle in the muscle was confirmed by putting the muscle through its range of motion and observing the resultant motion of the needle end. General anaesthesia, local anaesthesia and sedation were used according to the age of the patient, the number of sites to be injected and the particular needs of the patient.
- Following injection, it was noted that the onset of effects was complete within thirty six to seventy two hours and lasted from six to eighteen weeks. There were no systemic or local side-effects. All but one patient had some reduction in muscle tone; the one failure occurred early in the study and was probably the result of the toxin dosage administered (75 units) being sub-therapeutic. None of the patients developed extensive local hypotonicity. The majority of children had an improvement in function both subjectively and when measured objectively with gait analysis.
- Following injection of the calf muscle groups, an assessment was made of the passive dorsiflexion at the ankle. It was found that the younger children displayed a marked improvement in passive dorsiflexion, but that for children over six years there was little improvement. This was probably due to the dynamic contracture being replaced by a fixed contracture which was unresponsive to any amount of paresis.
- Case Study 1
- A five year old girl with moderate right hemiplegia underwent gait analysis and, on examination, was found to have dynamic contractures of her calf and hamstrings. Gait analysis recordings of saggital plane movements (with 95% confidence limits) were made prior to injection and these revealed that throughout the gait cycle, the knee was in excessive flexion. Gait analysis also indicated that she was in equinus throughout the gait cycle.
- Following injection, the knee could be extended nearly to neutral during stance and the gait analysis pattern, although still abnormal was much improved. The ankle traces recorded indicated that she was able to dorsiflex her ankle in gait and had developed a normal range of movements.
- Gait analysis was also undertaken at four months. At this stage the effects of the toxin had clinically worn off and it was found that the knee flexed to the same extent in swing that it did prior to injection. However, the gain of extension in stance was largely preserved. At the ankle, there was some relapse but there was still a lesser degree of equinus.
- Case Study 2
- Measurements were made of the maximal extension of the knee in a group of patients who underwent hamstring injection. Prior to injection, they all had some degree of dynamic knee flexion contracture. Four weeks following injection, this showed a highly significant improvement. However, the one patient who was least affected developed recurvatum at the knee following injection. After this, all patients who had a dynamic knee flexion contracture of less than fifteen degrees were excluded from hamstring injection. Only one local side-effect from the treatment was noted and this was a small subcutaneous haematoma which resolved itself in a few days.
- In cerebral palsy there is frequently a failure of muscle growth leading to fixed muscular contracture. This failure has also been demonstrated in the hereditary spastic mouse (Wright J and Rang M The Spastic Mouse. And the search for an animal model of spasticity in human beings) Clin. Orthop. 1990, 253, 12-19.
- A study has been carried out to ascertain the effect of Botulinum Toxin A on the growth of longitudinal muscle in the spastic mouse compared with normal siblings. Groups of spastic mice at six days old had one calf muscle injected with either 1.2 units of Botulinum toxin A or normal saline.
- The mice were sacrificed at maturity and the hind limbs dissected to allow measurement of the muscle and bones.
- In the control group, the spastic mice had a 13% failure of longitudinal muscle growth compared with their normal siblings. However, the muscles of the spastic mice injected with Botulinum had growth identical to that of their normal siblings. There was no difference in growth between normal mice injected with saline or Botulinum.
- It can be concluded that the injection of intramuscular Botulinum toxin during the growth period of the hereditary spastic mouse allows normal longitudinal muscle growth to take place and it is believed that this finding may have significance in the management of cerebral palsy.
- The invention has been illustrated by reference to Botulinum toxin A but it should be understood that the invention is not limited to the use of this toxin. For example, other Botulinum toxins may be employed. Moreover, other presynapnatic neurotoxins (e.g. of bacterial origin) which act in a manner similar to botulinum toxin may also be used. Also, synthetic analogues of the botulinum toxins may be envisaged wherein the 50 kd chain and/or the 100 kd chain are subjected to amino acid insertions, deletions and/or substitutions and, provided that such analogues retain the general type of activity exhibited by Botulinum toxin A, their use in the manner described hereinbefore is embraced by the present invention. The invention is also considered to embrace the use of substances structurally dissimilar to Botulinum toxin A, provided that such substances possess a prolonged ability to inhibit or block release of the synaptic vesicles containing acetylcholine.
Claims (4)
1-16. (canceled)
17. A vacuum dried, sterile, lyophilised, powdered formulation for therapeutic use in humans comprising:
(a) the neurotoxic component of a botulinum toxin purified from a complex of non-toxic proteins and haemagglutinins, wherein the neurotoxic component has a molecular weight of about 150 kilodaltons and comprises a short polypeptide chain of about 50 kD and a larger polypeptide chain of about 100 kD;
(b) saline, and;
(c) pasteurised human serum albumin.
18. A method for making a neurotoxic component botulinum toxin formulation comprising the steps of:
(a) establishing a culture of an anaerobic bacterium of Clostridium botulinum;
(b) growing a culture of the Clostridium botulinum in a fermenter;
(c) harvesting a botulinum toxin type A mixture from the fermenter, wherein the botulinum toxin type A harvested comprises;
(i) a neurotoxic polypeptide component with
(1) a molecular weight of about 150 kilodaltons,
(2) a short polypeptide chain of about 50 kD, and
(3) a larger polypeptide chain of about 100 kD,
(4) the two chains being linked together by a disulphide bridge,
(ii) a complex comprising
(5) non-toxic proteins and
(6) haemagglutinins,
(7) the complex having a molecular weight of about 900 kD;
(d) purifying the botulinum toxin type A neurotoxic component from the fermented mixture;
(e) adding human serum albumin as a stabilizer to the botulinum toxin type A;
(f) adding saline as a tonicity adjusting agent to the botulinum toxin type A to form a solution;
(g) sterile filtering the solution;
(h) vacuum drying the solution to form a powder;
(i) reconstituting the powder with sterile unpreserved normal saline to form a sterile, pyrogen-free aqueous solution or dispersion of a botulinum toxin type A neurotoxic component.
19. A product made by the method of claim 18.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/976,507 US20050112146A1 (en) | 1991-09-24 | 2004-10-29 | Botulinum toxin neurotoxic components formulations |
US11/752,096 US7378389B2 (en) | 1991-09-24 | 2007-05-22 | Botulinum toxin neurotoxic component for treating juvenile cerebral palsy |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9120306.7 | 1991-09-24 | ||
GB919120306A GB9120306D0 (en) | 1991-09-24 | 1991-09-24 | Method and compositions for the treatment of cerebral palsy |
US10/155,280 US20020142010A1 (en) | 1991-09-24 | 2002-05-22 | Method and compositions for the treatment of cerebral palsy |
US10/976,507 US20050112146A1 (en) | 1991-09-24 | 2004-10-29 | Botulinum toxin neurotoxic components formulations |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/155,280 Continuation US20020142010A1 (en) | 1991-09-24 | 2002-05-22 | Method and compositions for the treatment of cerebral palsy |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/752,096 Continuation US7378389B2 (en) | 1991-09-24 | 2007-05-22 | Botulinum toxin neurotoxic component for treating juvenile cerebral palsy |
Publications (1)
Publication Number | Publication Date |
---|---|
US20050112146A1 true US20050112146A1 (en) | 2005-05-26 |
Family
ID=10701881
Family Applications (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/211,352 Expired - Fee Related US6395277B1 (en) | 1991-09-24 | 1992-09-16 | Method and compositions for the treatment of cerebral palsy |
US09/900,380 Expired - Lifetime US6448231B2 (en) | 1991-09-24 | 2001-07-06 | Method and compositions for the treatment of cerebral palsy |
US10/155,280 Abandoned US20020142010A1 (en) | 1991-09-24 | 2002-05-22 | Method and compositions for the treatment of cerebral palsy |
US10/976,690 Abandoned US20050142150A1 (en) | 1991-09-24 | 2004-10-29 | Botulinum toxin formulations |
US10/976,507 Abandoned US20050112146A1 (en) | 1991-09-24 | 2004-10-29 | Botulinum toxin neurotoxic components formulations |
US11/752,096 Expired - Fee Related US7378389B2 (en) | 1991-09-24 | 2007-05-22 | Botulinum toxin neurotoxic component for treating juvenile cerebral palsy |
US12/111,904 Abandoned US20080206224A1 (en) | 1991-09-24 | 2008-04-29 | Muscle contraction treatment utilizing botulinum toxin |
Family Applications Before (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/211,352 Expired - Fee Related US6395277B1 (en) | 1991-09-24 | 1992-09-16 | Method and compositions for the treatment of cerebral palsy |
US09/900,380 Expired - Lifetime US6448231B2 (en) | 1991-09-24 | 2001-07-06 | Method and compositions for the treatment of cerebral palsy |
US10/155,280 Abandoned US20020142010A1 (en) | 1991-09-24 | 2002-05-22 | Method and compositions for the treatment of cerebral palsy |
US10/976,690 Abandoned US20050142150A1 (en) | 1991-09-24 | 2004-10-29 | Botulinum toxin formulations |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/752,096 Expired - Fee Related US7378389B2 (en) | 1991-09-24 | 2007-05-22 | Botulinum toxin neurotoxic component for treating juvenile cerebral palsy |
US12/111,904 Abandoned US20080206224A1 (en) | 1991-09-24 | 2008-04-29 | Muscle contraction treatment utilizing botulinum toxin |
Country Status (13)
Country | Link |
---|---|
US (7) | US6395277B1 (en) |
EP (1) | EP0605501B2 (en) |
JP (2) | JP3535872B2 (en) |
AT (1) | ATE178799T1 (en) |
AU (1) | AU666334B2 (en) |
CA (1) | CA2119562C (en) |
DE (1) | DE69228938T3 (en) |
DK (1) | DK0605501T5 (en) |
ES (1) | ES2131073T5 (en) |
GB (1) | GB9120306D0 (en) |
GR (1) | GR3030418T3 (en) |
NO (2) | NO312747B1 (en) |
WO (1) | WO1993005800A1 (en) |
Cited By (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030229034A1 (en) * | 2000-07-21 | 2003-12-11 | Essentia Biosystems, Inc. | Multi-component biological transport systems |
US20040014663A1 (en) * | 1993-12-28 | 2004-01-22 | Aoki Kei Roger | Botulinum toxin treatment for cervical dystonia |
US20040028703A1 (en) * | 2000-07-19 | 2004-02-12 | Hans Bigalke | Protein complex serving as a vehicle for orally administerable medicaments |
US20040126396A1 (en) * | 1993-12-28 | 2004-07-01 | Allergan, Inc. | Botulinum toxin treatment for strabismus |
US20040126397A1 (en) * | 1993-12-28 | 2004-07-01 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating various disorders and conditions and associated pain |
US20040151741A1 (en) * | 2002-12-20 | 2004-08-05 | Gary Borodic | Pharmaceutical botulinum toxin compositions |
US20040220100A1 (en) * | 2000-07-21 | 2004-11-04 | Essentia Biosystems, Inc. | Multi-component biological transport systems |
US20050196414A1 (en) * | 2004-03-03 | 2005-09-08 | Essentia Biosystems, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US20050239705A1 (en) * | 2004-03-03 | 2005-10-27 | Essentia Biosystems, Inc | Compositions and methods for topical diagnostic and therapeutic transport |
US20060182767A1 (en) * | 2002-05-28 | 2006-08-17 | Borodic Gary E | High-potency botulinum toxin formulations |
US20070116724A1 (en) * | 2005-11-17 | 2007-05-24 | Revance Therapeutics, Inc. | Compositions and Methods of Topical Application and Transdermal Delivery of Botulinum Toxins without Reduced Non-Toxin Proteins |
US20070202129A1 (en) * | 1993-12-28 | 2007-08-30 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for the treatment of pain associated with muscle activity or contracture |
US7378389B2 (en) | 1991-09-24 | 2008-05-27 | Allergan, Inc. | Botulinum toxin neurotoxic component for treating juvenile cerebral palsy |
US20080226551A1 (en) * | 2006-12-29 | 2008-09-18 | Revance Therapeutics, Inc. | Transport Molecules Using Reverse Sequence HIV-TAT Polypeptides |
US20080233152A1 (en) * | 2006-12-29 | 2008-09-25 | Revance Therapeutics, Inc. | Compositions and Methods of Topical Application and Transdermal Delivery of Botulinum Toxins Stabilized with Polypeptide Fragments Derived from HIV-TAT |
US20090087457A1 (en) * | 2005-03-03 | 2009-04-02 | Revance Therapeutics, Inc. | Compositions and Methods for Topical Application and Transdermal Delivery of Botulinum Toxins |
US20090247464A1 (en) * | 2005-03-03 | 2009-10-01 | Revance Therapeutics, Inc. | Compositions and Methods for Topical Application and Transdermal Delivery of an Oligopeptide |
US20100124559A1 (en) * | 2008-11-20 | 2010-05-20 | Allergan, Inc. | Early Treatment and Prevention of Increased Muscle Tonicity |
US20140044695A1 (en) * | 2005-08-01 | 2014-02-13 | Allergan, Inc. | Botulinum toxin compositions |
US9211248B2 (en) | 2004-03-03 | 2015-12-15 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US9901627B2 (en) | 2014-07-18 | 2018-02-27 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
US9950042B2 (en) | 2008-12-04 | 2018-04-24 | Revance Therapeutics, Inc. | Extended length botulinum toxin formulation for human or mammalian use |
US10857215B2 (en) | 2012-04-12 | 2020-12-08 | Revance Therapeutics, Inc. | Use of botulinum toxin for the treatment of cerebrovascular disease, renovascular and retinovascular circulatory beds |
WO2022075785A1 (en) * | 2020-10-07 | 2022-04-14 | 주식회사 프로톡스 | Vacuum drying method for botulinum toxin |
US11484580B2 (en) | 2014-07-18 | 2022-11-01 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
Families Citing this family (92)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996012802A1 (en) * | 1989-10-31 | 1996-05-02 | Ophidian Pharmaceuticals, Inc. | Vaccine and antitoxin for treatment and prevention of c. difficile disease |
US5919665A (en) | 1989-10-31 | 1999-07-06 | Ophidian Pharmaceuticals, Inc. | Vaccine for clostridium botulinum neurotoxin |
US7384918B2 (en) * | 1991-09-24 | 2008-06-10 | Allergan, Inc. | Botulinum toxin for treating muscle contracture |
US6939852B2 (en) * | 1991-09-24 | 2005-09-06 | Allergan, Inc. | Methods and compositions for the treatment of cerebral palsy |
AU4646393A (en) * | 1992-06-23 | 1994-01-24 | Interactive Biologics Associates | Pharmaceutical composition containing botulinum b complex |
ES2194025T3 (en) * | 1993-06-10 | 2003-11-16 | Allergan Inc | MULTIPLE BOTULINIC TOXINS TO TREAT DISORDERS AND NEUROMUSCULAR DISEASES. |
EP1099445A3 (en) * | 1993-06-10 | 2001-09-05 | Allergan, Inc. | Treatment of neuromuscular disorders and conditions with different botulinum serotype |
US5437291A (en) * | 1993-08-26 | 1995-08-01 | Univ Johns Hopkins | Method for treating gastrointestinal muscle disorders and other smooth muscle dysfunction |
AU2007202480B2 (en) * | 1993-12-28 | 2009-01-29 | Allergan, Inc. | Method for treating pain associated with a muscle disorder |
EP2027872B1 (en) * | 1993-12-28 | 2010-07-14 | Allergan, Inc. | Neurotoxic component of a botulinum toxin for treating tardive dyskinesia |
US5766605A (en) * | 1994-04-15 | 1998-06-16 | Mount Sinai School Of Medicine Of The City University Of New York | Treatment of autonomic nerve dysfunction with botulinum toxin |
US5670484A (en) * | 1994-05-09 | 1997-09-23 | Binder; William J. | Method for treatment of skin lesions associated with cutaneous cell-proliferative disorders |
PT1086702E (en) * | 1994-05-09 | 2005-08-31 | William J Binder | PRE-SYNAPTIC NEUROTOXINS FOR THE TREATMENT OF CABBAGE PAIN DUE TO ENXAQUECA |
EP1053014A4 (en) | 1998-01-26 | 2004-11-10 | Univ Massachusetts | BIOLOGICALLY ACTIVE HEMAGGLUTININ FROM TYPE A $i(CLOSTRIDIUM BOTULINUM) AND METHODS OF USE |
TW574036B (en) | 1998-09-11 | 2004-02-01 | Elan Pharm Inc | Stable liquid compositions of botulinum toxin |
US6337075B1 (en) * | 2000-01-11 | 2002-01-08 | Allergan Sales, Inc. | Methods for treating diabetes |
US20040033241A1 (en) * | 2000-06-02 | 2004-02-19 | Allergan, Inc. | Controlled release botulinum toxin system |
US20040170665A1 (en) * | 2000-06-02 | 2004-09-02 | Allergan, Inc. | Intravitreal botulinum toxin implant |
US6306403B1 (en) | 2000-06-14 | 2001-10-23 | Allergan Sales, Inc. | Method for treating parkinson's disease with a botulinum toxin |
MXPA03000014A (en) * | 2000-06-28 | 2004-09-13 | Ira Sanders | Methods for using tetanus toxin for benificial purposes in animals (mammals). |
US7691983B2 (en) * | 2000-07-21 | 2010-04-06 | Allergan, Inc. | Chimera botulinum toxin type E |
US20040219619A1 (en) * | 2000-07-21 | 2004-11-04 | Ester Fernandez-Salas | Methods of identifying compounds that alter toxin persistence and/or protease activity |
US6903187B1 (en) * | 2000-07-21 | 2005-06-07 | Allergan, Inc. | Leucine-based motif and clostridial neurotoxins |
US7491799B2 (en) * | 2000-07-21 | 2009-02-17 | Allergan, Inc. | Modified botulinum neurotoxins |
ITUD20010002A1 (en) * | 2001-01-05 | 2002-07-05 | Univ Degli Studi Udine | USE OF BOTULIN TOXIN FOR THE SOLUTION OF JOINT PATHOLOGIES, IN PARTICULAR OF COXARTROSIS, EPICONDYLITIS AND PATHOLUS |
JP4707254B2 (en) * | 2001-04-24 | 2011-06-22 | クミアイ化学工業株式会社 | Granular composition and method for producing the same |
CN102349914B (en) | 2001-11-15 | 2015-01-28 | 微观藻类公司 | Pharmaceutical compositions containing 3, 4-propinoperhydropurines and uses thereof for blocking neuronal transmission |
US7763663B2 (en) * | 2001-12-19 | 2010-07-27 | University Of Massachusetts | Polysaccharide-containing block copolymer particles and uses thereof |
US20050163809A1 (en) * | 2002-03-29 | 2005-07-28 | Ryuji Kaji | Remedy for hypermyotonia |
US6776991B2 (en) | 2002-06-26 | 2004-08-17 | Allergan, Inc. | Methods for treating priapism |
US20040086532A1 (en) * | 2002-11-05 | 2004-05-06 | Allergan, Inc., | Botulinum toxin formulations for oral administration |
US7238357B2 (en) | 2002-11-05 | 2007-07-03 | Allergan, Inc. | Methods for treating ulcers and gastroesophageal reflux disease |
MXPA05009425A (en) * | 2003-03-06 | 2006-02-10 | Botulinum Toxin Res Ass Inc | Treatment of sinusitis related chronic facial pain and headache with botulinum toxin. |
US7393537B2 (en) * | 2003-04-25 | 2008-07-01 | Allergan, Inc. | Botulinum toxin for treatment of obsessive compulsive finger biting disorder |
US7393538B2 (en) * | 2003-04-25 | 2008-07-01 | Ackerman Alan H | Clostridial toxin treatment for dermatillomania |
US7396535B2 (en) * | 2003-04-25 | 2008-07-08 | Ackerman Alan H | Therapy for obsessive compulsive head banging |
US7422753B2 (en) * | 2003-04-25 | 2008-09-09 | Allergan, Inc. | Methods for treating trichotillomania |
US7390496B2 (en) * | 2003-04-25 | 2008-06-24 | Allergan, Inc. | Therapeutic treatments for repetitive hand washing |
US6838434B2 (en) * | 2003-05-02 | 2005-01-04 | Allergan, Inc. | Methods for treating sinus headache |
US20040226556A1 (en) | 2003-05-13 | 2004-11-18 | Deem Mark E. | Apparatus for treating asthma using neurotoxin |
US7220422B2 (en) | 2003-05-20 | 2007-05-22 | Allergan, Inc. | Methods and compositions for treating eye disorders |
US20040253274A1 (en) * | 2003-06-11 | 2004-12-16 | Allergan, Inc. | Use of a clostridial toxin to reduce appetite |
US20050013850A1 (en) * | 2003-07-15 | 2005-01-20 | Caers Jan K. | Device to assist hyperhydrosis therapy |
US8609113B2 (en) | 2003-10-29 | 2013-12-17 | Allergan, Inc. | Botulinum toxin treatments of depression |
US8617572B2 (en) * | 2003-10-29 | 2013-12-31 | Allergan, Inc. | Botulinum toxin treatments of depression |
US8734810B2 (en) | 2003-10-29 | 2014-05-27 | Allergan, Inc. | Botulinum toxin treatments of neurological and neuropsychiatric disorders |
US8609112B2 (en) | 2003-10-29 | 2013-12-17 | Allergan, Inc. | Botulinum toxin treatments of depression |
US7172764B2 (en) * | 2003-11-17 | 2007-02-06 | Allergan, Inc. | Rescue agents for treating botulinum toxin intoxications |
US20050129677A1 (en) * | 2003-12-10 | 2005-06-16 | Shengwen Li | Lipid rafts and clostridial toxins |
US20050148935A1 (en) * | 2003-12-29 | 2005-07-07 | Rozalina Dimitrova | Botulinum toxin injection guide |
US20050206225A1 (en) * | 2004-03-18 | 2005-09-22 | Ford Global Technologies, Llc | Method and apparatus for predicting the position of a trailer relative to a vehicle |
EP1824488B1 (en) * | 2004-05-07 | 2017-08-09 | Algenis SpA | Phycotoxins and uses thereof |
CA2607206C (en) * | 2004-05-07 | 2016-06-14 | Phytotox Limited | Transdermal administration of phycotoxins |
US20080045889A1 (en) * | 2004-07-21 | 2008-02-21 | Gerondale Scott J | Botoxo Needle Injector |
US20060024794A1 (en) * | 2004-07-30 | 2006-02-02 | Shengwen Li | Novel methods for production of di-chain botulinum toxin |
US20080274195A1 (en) | 2005-07-18 | 2008-11-06 | University Of Massachusetts Lowell | Compositions and Methods for Making and Using Nanoemulsions |
US10052465B2 (en) | 2005-07-22 | 2018-08-21 | The Foundry, Llc | Methods and systems for toxin delivery to the nasal cavity |
US9511210B2 (en) * | 2006-05-19 | 2016-12-06 | The Foundry, Llc | Apparatus for toxin delivery to the nasal cavity |
WO2007014003A2 (en) | 2005-07-22 | 2007-02-01 | The Foundry Inc. | Systems and methods for delivery of a therapeutic agent |
US7910116B2 (en) | 2005-08-24 | 2011-03-22 | Allergan, Inc. | Use of a botulinum toxin to improve gastric emptying and/or to treat GERD |
PT3144013T (en) | 2005-12-01 | 2019-02-07 | Univ Massachusetts Lowell | Botulinum nanoemulsions |
US9486408B2 (en) | 2005-12-01 | 2016-11-08 | University Of Massachusetts Lowell | Botulinum nanoemulsions |
US7794386B2 (en) | 2006-03-15 | 2010-09-14 | Allergan, Inc. | Methods for facilitating weight loss |
US7811586B2 (en) | 2006-05-02 | 2010-10-12 | Allergan, Inc. | Methods for alleviating testicular pain |
US10792344B2 (en) | 2006-06-29 | 2020-10-06 | Merz Pharma Gmbh & Co. Kgaa | High frequency application of botulinum toxin therapy |
AR061669A1 (en) | 2006-06-29 | 2008-09-10 | Merz Pharma Gmbh & Co Kgaa | HIGH FREQUENCY THERAPY APPLICATION WITH BOTULIN TOXIN |
US20080092910A1 (en) * | 2006-10-18 | 2008-04-24 | Allergan, Inc. | Apparatus and method for treating obesity using neurotoxins in conjunction with bariatric procedures |
US20080113051A1 (en) * | 2006-11-13 | 2008-05-15 | Allergan, Inc. | Methods for alleviating tattoo pain |
US20100150994A1 (en) | 2006-12-01 | 2010-06-17 | Anterios, Inc. | Amphiphilic entity nanoparticles |
CA2671133C (en) * | 2006-12-01 | 2015-11-24 | Anterios, Inc. | Peptide nanoparticles and uses therefor |
CN101765423B (en) | 2007-05-31 | 2014-08-06 | 安特里奥公司 | Nucleic acid nanoparticles and uses therefor |
US8483831B1 (en) | 2008-02-15 | 2013-07-09 | Holaira, Inc. | System and method for bronchial dilation |
US8470337B2 (en) * | 2008-03-13 | 2013-06-25 | Allergan, Inc. | Therapeutic treatments using botulinum neurotoxin |
WO2009137819A1 (en) | 2008-05-09 | 2009-11-12 | Innovative Pulmonary Solutions, Inc. | Systems, assemblies, and methods for treating a bronchial tree |
WO2009158687A1 (en) * | 2008-06-26 | 2009-12-30 | Anterios, Inc. | Dermal delivery |
WO2010029554A1 (en) | 2008-09-11 | 2010-03-18 | I.B.R. Israeli Biotechnology Research Ltd. | Leucojum bulb extracts and use thereof |
US8506970B2 (en) * | 2008-10-14 | 2013-08-13 | Dt Scimed, Llc | Dose and localization of botulinum toxins in skin and muscle |
JP4697289B2 (en) | 2008-11-05 | 2011-06-08 | ソニー株式会社 | Imaging apparatus and display control method for imaging apparatus |
US8147848B2 (en) | 2009-08-26 | 2012-04-03 | Allergan, Inc. | Method for treating premature ejaculation with a botulinum neurotoxin |
WO2011056684A2 (en) | 2009-10-27 | 2011-05-12 | Innovative Pulmonary Solutions, Inc. | Delivery devices with coolable energy emitting assemblies |
KR101820542B1 (en) | 2009-11-11 | 2018-01-19 | 호라이라 인코포레이티드 | Systems, apparatuses, and methods for treating tissue and controlling stenosis |
US8911439B2 (en) | 2009-11-11 | 2014-12-16 | Holaira, Inc. | Non-invasive and minimally invasive denervation methods and systems for performing the same |
US8992941B2 (en) | 2011-07-08 | 2015-03-31 | Allergan, Inc. | Method for treatment of esophageal spasm |
AU2012282873B2 (en) | 2011-07-08 | 2016-03-31 | Allergan, Inc. | Method for treatment of autonomic nervous system disorders |
JP6092205B2 (en) | 2011-07-14 | 2017-03-08 | アラーガン、インコーポレイテッドAllergan,Incorporated | How to treat incontinence related to sexual activity |
CN103702681A (en) | 2011-07-20 | 2014-04-02 | 阿勒根公司 | Botulinum toxins for use in a method for treatment of adipose deposits |
WO2014048740A1 (en) | 2012-09-25 | 2014-04-03 | Haldor Topsøe A/S | Steam reforming catalyst and method of making thereof |
US9398933B2 (en) | 2012-12-27 | 2016-07-26 | Holaira, Inc. | Methods for improving drug efficacy including a combination of drug administration and nerve modulation |
US10149893B2 (en) | 2013-09-24 | 2018-12-11 | Allergan, Inc. | Methods for modifying progression of osteoarthritis |
EP3319603B1 (en) | 2015-07-08 | 2021-11-17 | Gilrose Pharmaceuticals, LLC | Use of methylphenidate for the treatment of gait and limb impairment secondary to pre-frontal cortex processing disorder |
BR112019010131A2 (en) | 2016-11-21 | 2019-10-08 | Eirion Therapeutics Inc | transdermal delivery of large agents |
EP3801581A4 (en) * | 2018-05-24 | 2022-04-06 | Children's Hospital Medical Center | Compositions and methods for the treatment of muscle contractures |
Citations (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2373454A (en) * | 1943-07-09 | 1945-04-10 | Squibb & Sons Inc | Method of preparing tetanus toxin |
US2719102A (en) * | 1949-10-28 | 1955-09-27 | Corn States Serum Company | Clostridium perfringens toxoid and process of making the same |
US3132995A (en) * | 1961-10-20 | 1964-05-12 | Carter Prod Inc | Endotoxin fractions and method for producing same |
US4234566A (en) * | 1979-06-29 | 1980-11-18 | Packman Elias W | Antihistamine and methods for use thereof |
US4713240A (en) * | 1985-04-04 | 1987-12-15 | Research Corporation | Vaccines based on insoluble supports |
US4720494A (en) * | 1984-11-05 | 1988-01-19 | The Gillette Company | Anticholinergic eucatropine esters and antiperspirant use thereof |
US4932936A (en) * | 1988-01-29 | 1990-06-12 | Regents Of The University Of Minnesota | Method and device for pharmacological control of spasticity |
US4935969A (en) * | 1987-12-02 | 1990-06-26 | Farnsworth Orin J | Method and device for the controlled disposal of human waste |
US5055302A (en) * | 1990-02-22 | 1991-10-08 | Trustees Of The University Of Pennsylvania | Neuropeptide control of ocular growth |
US5055291A (en) * | 1986-11-04 | 1991-10-08 | Baylor College Of Medicine | Compositions for preventing secondary cataracts |
US5056291A (en) * | 1989-10-19 | 1991-10-15 | Skilland Engineering, Ltd. | Modular system for space frame structures |
US5183462A (en) * | 1990-08-21 | 1993-02-02 | Associated Synapse Biologics | Controlled administration of chemodenervating pharmaceuticals |
US5401243A (en) * | 1990-08-21 | 1995-03-28 | Associated Synapse Biologics | Controlled administration of chemodenervating pharmaceuticals |
US5437291A (en) * | 1993-08-26 | 1995-08-01 | Univ Johns Hopkins | Method for treating gastrointestinal muscle disorders and other smooth muscle dysfunction |
US5512547A (en) * | 1994-10-13 | 1996-04-30 | Wisconsin Alumni Research Foundation | Pharmaceutical composition of botulinum neurotoxin and method of preparation |
US5562907A (en) * | 1993-05-14 | 1996-10-08 | Arnon; Stephen S. | Method to prevent side-effects and insensitivity to the therapeutic uses of toxins |
US5696077A (en) * | 1992-06-23 | 1997-12-09 | Associated Synapse Biologics | Pharmaceutical composition containing botulinum B complex |
US5766605A (en) * | 1994-04-15 | 1998-06-16 | Mount Sinai School Of Medicine Of The City University Of New York | Treatment of autonomic nerve dysfunction with botulinum toxin |
US6113915A (en) * | 1999-10-12 | 2000-09-05 | Allergan Sales, Inc. | Methods for treating pain |
US20010018415A1 (en) * | 1993-12-28 | 2001-08-30 | Aoki K. Roger | Method for treating tardive dyskinesia with botulinum toxin type B |
US6306403B1 (en) * | 2000-06-14 | 2001-10-23 | Allergan Sales, Inc. | Method for treating parkinson's disease with a botulinum toxin |
US6395277B1 (en) * | 1991-09-24 | 2002-05-28 | Allergan | Method and compositions for the treatment of cerebral palsy |
US20020102275A1 (en) * | 1991-09-24 | 2002-08-01 | Allergan Sales, Inc. | Methods and compositions for the treatment of cerebral palsy |
US6500436B2 (en) * | 2000-01-19 | 2002-12-31 | Allergan, Inc. | Clostridial toxin derivatives and methods for treating pain |
US20030118598A1 (en) * | 2000-02-08 | 2003-06-26 | Allergan, Inc. | Clostridial toxin pharmaceutical compositions |
US6623742B2 (en) * | 2001-09-17 | 2003-09-23 | Allergan, Inc. | Methods for treating fibromyalgia |
US20040014663A1 (en) * | 1993-12-28 | 2004-01-22 | Aoki Kei Roger | Botulinum toxin treatment for cervical dystonia |
US20040126397A1 (en) * | 1993-12-28 | 2004-07-01 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating various disorders and conditions and associated pain |
US20040126396A1 (en) * | 1993-12-28 | 2004-07-01 | Allergan, Inc. | Botulinum toxin treatment for strabismus |
US6872397B2 (en) * | 1993-06-10 | 2005-03-29 | Allergan, Inc. | Method for treating neuromuscular disorders and conditions with botulinum toxin types A and B |
US6986893B2 (en) * | 1993-12-28 | 2006-01-17 | Allergan, Inc. | Method for treating a mucus secretion |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0262396A3 (en) | 1986-09-20 | 1989-08-23 | Heinz Dipl.-Ing. Hölter | Process for the preparation of calcium sulphate dihydrate during flue-gas desulfurization |
US5053005A (en) * | 1989-04-21 | 1991-10-01 | Gary E. Borodic | Chemomodulation of curvature of the juvenile spine |
US7384918B2 (en) * | 1991-09-24 | 2008-06-10 | Allergan, Inc. | Botulinum toxin for treating muscle contracture |
FR2692475B1 (en) | 1992-06-19 | 2000-04-21 | Montpellier Chirurgie | TOTAL KNEE PROSTHESIS. |
JPH06192296A (en) | 1992-10-28 | 1994-07-12 | Chiba Pref Gov | Production of crystal a type botulinus toxin as medicine for therapy |
WO1994015629A1 (en) | 1993-01-15 | 1994-07-21 | Associated Synapse Biologics | Method for treating myofascial pain syndrome |
ES2194025T3 (en) | 1993-06-10 | 2003-11-16 | Allergan Inc | MULTIPLE BOTULINIC TOXINS TO TREAT DISORDERS AND NEUROMUSCULAR DISEASES. |
EP2027872B1 (en) | 1993-12-28 | 2010-07-14 | Allergan, Inc. | Neurotoxic component of a botulinum toxin for treating tardive dyskinesia |
PT1086702E (en) | 1994-05-09 | 2005-08-31 | William J Binder | PRE-SYNAPTIC NEUROTOXINS FOR THE TREATMENT OF CABBAGE PAIN DUE TO ENXAQUECA |
TWI243265B (en) | 2002-02-27 | 2005-11-11 | Chi Mei Optoelectronics Corp | Method for forming a reflection-type light diffuser |
-
1991
- 1991-09-24 GB GB919120306A patent/GB9120306D0/en active Pending
-
1992
- 1992-09-16 CA CA002119562A patent/CA2119562C/en not_active Expired - Lifetime
- 1992-09-16 US US08/211,352 patent/US6395277B1/en not_active Expired - Fee Related
- 1992-09-16 JP JP50589693A patent/JP3535872B2/en not_active Expired - Lifetime
- 1992-09-16 DK DK92919570T patent/DK0605501T5/en active
- 1992-09-16 AT AT92919570T patent/ATE178799T1/en active
- 1992-09-16 WO PCT/GB1992/001697 patent/WO1993005800A1/en active IP Right Grant
- 1992-09-16 AU AU25664/92A patent/AU666334B2/en not_active Expired
- 1992-09-16 EP EP92919570A patent/EP0605501B2/en not_active Expired - Lifetime
- 1992-09-16 DE DE69228938T patent/DE69228938T3/en not_active Expired - Lifetime
- 1992-09-16 ES ES92919570T patent/ES2131073T5/en not_active Expired - Lifetime
-
1994
- 1994-03-23 NO NO19941065A patent/NO312747B1/en not_active IP Right Cessation
-
1999
- 1999-06-03 GR GR990401502T patent/GR3030418T3/en unknown
-
2001
- 2001-07-06 JP JP2001206187A patent/JP2002097154A/en active Pending
- 2001-07-06 US US09/900,380 patent/US6448231B2/en not_active Expired - Lifetime
- 2001-07-30 NO NO20013727A patent/NO324159B1/en not_active IP Right Cessation
-
2002
- 2002-05-22 US US10/155,280 patent/US20020142010A1/en not_active Abandoned
-
2004
- 2004-10-29 US US10/976,690 patent/US20050142150A1/en not_active Abandoned
- 2004-10-29 US US10/976,507 patent/US20050112146A1/en not_active Abandoned
-
2007
- 2007-05-22 US US11/752,096 patent/US7378389B2/en not_active Expired - Fee Related
-
2008
- 2008-04-29 US US12/111,904 patent/US20080206224A1/en not_active Abandoned
Patent Citations (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2373454A (en) * | 1943-07-09 | 1945-04-10 | Squibb & Sons Inc | Method of preparing tetanus toxin |
US2719102A (en) * | 1949-10-28 | 1955-09-27 | Corn States Serum Company | Clostridium perfringens toxoid and process of making the same |
US3132995A (en) * | 1961-10-20 | 1964-05-12 | Carter Prod Inc | Endotoxin fractions and method for producing same |
US4234566A (en) * | 1979-06-29 | 1980-11-18 | Packman Elias W | Antihistamine and methods for use thereof |
US4720494A (en) * | 1984-11-05 | 1988-01-19 | The Gillette Company | Anticholinergic eucatropine esters and antiperspirant use thereof |
US4713240A (en) * | 1985-04-04 | 1987-12-15 | Research Corporation | Vaccines based on insoluble supports |
US5055291A (en) * | 1986-11-04 | 1991-10-08 | Baylor College Of Medicine | Compositions for preventing secondary cataracts |
US4935969A (en) * | 1987-12-02 | 1990-06-26 | Farnsworth Orin J | Method and device for the controlled disposal of human waste |
US4932936A (en) * | 1988-01-29 | 1990-06-12 | Regents Of The University Of Minnesota | Method and device for pharmacological control of spasticity |
US5056291A (en) * | 1989-10-19 | 1991-10-15 | Skilland Engineering, Ltd. | Modular system for space frame structures |
US5055302A (en) * | 1990-02-22 | 1991-10-08 | Trustees Of The University Of Pennsylvania | Neuropeptide control of ocular growth |
US5183462A (en) * | 1990-08-21 | 1993-02-02 | Associated Synapse Biologics | Controlled administration of chemodenervating pharmaceuticals |
US5298019A (en) * | 1990-08-21 | 1994-03-29 | Associated Synapse Biologics | Controlled administration of chemodenervating pharmaceuticals |
US5401243A (en) * | 1990-08-21 | 1995-03-28 | Associated Synapse Biologics | Controlled administration of chemodenervating pharmaceuticals |
US6395277B1 (en) * | 1991-09-24 | 2002-05-28 | Allergan | Method and compositions for the treatment of cerebral palsy |
US6939852B2 (en) * | 1991-09-24 | 2005-09-06 | Allergan, Inc. | Methods and compositions for the treatment of cerebral palsy |
US6448231B2 (en) * | 1991-09-24 | 2002-09-10 | Allergan, Inc. | Method and compositions for the treatment of cerebral palsy |
US20020102275A1 (en) * | 1991-09-24 | 2002-08-01 | Allergan Sales, Inc. | Methods and compositions for the treatment of cerebral palsy |
US5696077A (en) * | 1992-06-23 | 1997-12-09 | Associated Synapse Biologics | Pharmaceutical composition containing botulinum B complex |
US5562907A (en) * | 1993-05-14 | 1996-10-08 | Arnon; Stephen S. | Method to prevent side-effects and insensitivity to the therapeutic uses of toxins |
US6872397B2 (en) * | 1993-06-10 | 2005-03-29 | Allergan, Inc. | Method for treating neuromuscular disorders and conditions with botulinum toxin types A and B |
US5437291A (en) * | 1993-08-26 | 1995-08-01 | Univ Johns Hopkins | Method for treating gastrointestinal muscle disorders and other smooth muscle dysfunction |
US6683049B1 (en) * | 1993-12-28 | 2004-01-27 | Allergan, Inc. | Method for treating a cholinergic influenced sweat gland |
US20040126396A1 (en) * | 1993-12-28 | 2004-07-01 | Allergan, Inc. | Botulinum toxin treatment for strabismus |
US6986893B2 (en) * | 1993-12-28 | 2006-01-17 | Allergan, Inc. | Method for treating a mucus secretion |
US6974578B1 (en) * | 1993-12-28 | 2005-12-13 | Allergan, Inc. | Method for treating secretions and glands using botulinum toxin |
US6887476B2 (en) * | 1993-12-28 | 2005-05-03 | Allergan, Inc. | Method for treating pain with botulinum toxin type B |
US6290961B1 (en) * | 1993-12-28 | 2001-09-18 | Allergan, Inc. | Method for treating dystonia with botulinum toxin type B |
US20010018415A1 (en) * | 1993-12-28 | 2001-08-30 | Aoki K. Roger | Method for treating tardive dyskinesia with botulinum toxin type B |
US20050084504A1 (en) * | 1993-12-28 | 2005-04-21 | Allergan, Inc. | Methods for treating various disorders with a neurotoxic component of a botulinum toxin |
US6319505B1 (en) * | 1993-12-28 | 2001-11-20 | Allergan Sales, Inc. | Method for treating dystonia with botulinum toxin types C to G |
US6841156B2 (en) * | 1993-12-28 | 2005-01-11 | Allergan, Inc. | Method for treating muscle spasm with botulinum toxin type B |
US20040014663A1 (en) * | 1993-12-28 | 2004-01-22 | Aoki Kei Roger | Botulinum toxin treatment for cervical dystonia |
US20040151740A1 (en) * | 1993-12-28 | 2004-08-05 | Aoki Kei Roger | Botulinum toxin treatment for blepharospasm |
US20040126397A1 (en) * | 1993-12-28 | 2004-07-01 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating various disorders and conditions and associated pain |
US5766605A (en) * | 1994-04-15 | 1998-06-16 | Mount Sinai School Of Medicine Of The City University Of New York | Treatment of autonomic nerve dysfunction with botulinum toxin |
US5512547A (en) * | 1994-10-13 | 1996-04-30 | Wisconsin Alumni Research Foundation | Pharmaceutical composition of botulinum neurotoxin and method of preparation |
US6113915A (en) * | 1999-10-12 | 2000-09-05 | Allergan Sales, Inc. | Methods for treating pain |
US6372226B2 (en) * | 1999-10-12 | 2002-04-16 | Allergan Sales, Inc. | Intraspinal botulinum toxin for treating pain |
US6333037B1 (en) * | 1999-10-12 | 2001-12-25 | Allergan Sales Inc. | Methods for treating pain with a modified neurotoxin |
US6500436B2 (en) * | 2000-01-19 | 2002-12-31 | Allergan, Inc. | Clostridial toxin derivatives and methods for treating pain |
US20030118598A1 (en) * | 2000-02-08 | 2003-06-26 | Allergan, Inc. | Clostridial toxin pharmaceutical compositions |
US6306403B1 (en) * | 2000-06-14 | 2001-10-23 | Allergan Sales, Inc. | Method for treating parkinson's disease with a botulinum toxin |
US6623742B2 (en) * | 2001-09-17 | 2003-09-23 | Allergan, Inc. | Methods for treating fibromyalgia |
Cited By (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7378389B2 (en) | 1991-09-24 | 2008-05-27 | Allergan, Inc. | Botulinum toxin neurotoxic component for treating juvenile cerebral palsy |
US8557256B2 (en) | 1993-12-28 | 2013-10-15 | Allergan, Inc. | Treatment for cervical dystonia with the neurotoxic component of a botulinum toxin |
US20070202129A1 (en) * | 1993-12-28 | 2007-08-30 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for the treatment of pain associated with muscle activity or contracture |
US20040014663A1 (en) * | 1993-12-28 | 2004-01-22 | Aoki Kei Roger | Botulinum toxin treatment for cervical dystonia |
US20040126397A1 (en) * | 1993-12-28 | 2004-07-01 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating various disorders and conditions and associated pain |
US8052980B2 (en) | 1993-12-28 | 2011-11-08 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating arthritis |
US20090318360A1 (en) * | 1993-12-28 | 2009-12-24 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating arthritis |
US8187612B2 (en) | 1993-12-28 | 2012-05-29 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating a spastic muscle |
US20040126396A1 (en) * | 1993-12-28 | 2004-07-01 | Allergan, Inc. | Botulinum toxin treatment for strabismus |
US20080107762A1 (en) * | 1993-12-28 | 2008-05-08 | Allergan, Inc. | Neurotoxin component treatment for spasticity |
US8216995B2 (en) | 1993-12-28 | 2012-07-10 | Allergan, Inc. | Botulinum toxin treatments |
US7501130B2 (en) | 1993-12-28 | 2009-03-10 | Allergan, Inc. | Methods for treating myofascial pain |
US20080107763A1 (en) * | 1993-12-28 | 2008-05-08 | Allergan, Inc. | Use of the neurotoxic component of a botulinum toxin for treating a spastic muscle |
US20040028703A1 (en) * | 2000-07-19 | 2004-02-12 | Hans Bigalke | Protein complex serving as a vehicle for orally administerable medicaments |
US20030229034A1 (en) * | 2000-07-21 | 2003-12-11 | Essentia Biosystems, Inc. | Multi-component biological transport systems |
US7807780B2 (en) | 2000-07-21 | 2010-10-05 | Revance Therapeutics, Inc. | Multi-component biological transport systems |
US20040220100A1 (en) * | 2000-07-21 | 2004-11-04 | Essentia Biosystems, Inc. | Multi-component biological transport systems |
US20060182767A1 (en) * | 2002-05-28 | 2006-08-17 | Borodic Gary E | High-potency botulinum toxin formulations |
US7691394B2 (en) | 2002-05-28 | 2010-04-06 | Botulinum Toxin Research Associates, Inc. | High-potency botulinum toxin formulations |
US7491403B2 (en) * | 2002-12-20 | 2009-02-17 | Botulinum Toxin Research Associates | Pharmaceutical botulinum toxin compositions |
US20040151741A1 (en) * | 2002-12-20 | 2004-08-05 | Gary Borodic | Pharmaceutical botulinum toxin compositions |
US20080038203A1 (en) * | 2004-03-03 | 2008-02-14 | Revance Therapeutics, Inc. | Compositions and Methods for Topical Diagnostic and Therapeutic Transport |
US8974774B2 (en) | 2004-03-03 | 2015-03-10 | Revance Therapeutics, Inc. | Compositions and methods for topical diagnostic and therapeutic transport |
US8092788B2 (en) | 2004-03-03 | 2012-01-10 | Revance Therapeutics, Inc. | Compositions and methods for topical diagnostic and therapeutic transport |
US8404249B2 (en) | 2004-03-03 | 2013-03-26 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US8398997B2 (en) | 2004-03-03 | 2013-03-19 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US10172877B2 (en) | 2004-03-03 | 2019-01-08 | Revance Therapeutics, Inc. | Compositions and methods for topical diagnostic and therapeutic transport |
US20050239705A1 (en) * | 2004-03-03 | 2005-10-27 | Essentia Biosystems, Inc | Compositions and methods for topical diagnostic and therapeutic transport |
US20050196414A1 (en) * | 2004-03-03 | 2005-09-08 | Essentia Biosystems, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US9211248B2 (en) | 2004-03-03 | 2015-12-15 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US9180081B2 (en) | 2005-03-03 | 2015-11-10 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US20090087457A1 (en) * | 2005-03-03 | 2009-04-02 | Revance Therapeutics, Inc. | Compositions and Methods for Topical Application and Transdermal Delivery of Botulinum Toxins |
US10744078B2 (en) | 2005-03-03 | 2020-08-18 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US10080786B2 (en) | 2005-03-03 | 2018-09-25 | Revance Therapeutics, Inc. | Methods for treating pain by topical application and transdermal delivery of botulinum toxin |
US20090247464A1 (en) * | 2005-03-03 | 2009-10-01 | Revance Therapeutics, Inc. | Compositions and Methods for Topical Application and Transdermal Delivery of an Oligopeptide |
US8022179B2 (en) | 2005-03-03 | 2011-09-20 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of an oligopeptide |
US9314416B2 (en) | 2005-03-03 | 2016-04-19 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
US9629904B2 (en) * | 2005-08-01 | 2017-04-25 | Allergan, Inc. | Botulinum toxin compositions |
US20140044695A1 (en) * | 2005-08-01 | 2014-02-13 | Allergan, Inc. | Botulinum toxin compositions |
US20090163412A1 (en) * | 2005-11-17 | 2009-06-25 | Revance Therapeuticals, Inc. | Compositions and Methods of Topical Application and Transdermal Delivery of Botulinum Toxins with Reduced Non-Toxin Proteins |
US8568740B2 (en) | 2005-11-17 | 2013-10-29 | Revance Therapeutics, Inc. | Compositions and methods of topical application and transdermal delivery of botulinum toxins with reduced non-toxin proteins |
US8518414B2 (en) | 2005-11-17 | 2013-08-27 | Revance Therapeutics, Inc. | Compositions and methods of topical application and transdermal delivery of botulinum toxins with reduced non-toxin proteins |
US20070116724A1 (en) * | 2005-11-17 | 2007-05-24 | Revance Therapeutics, Inc. | Compositions and Methods of Topical Application and Transdermal Delivery of Botulinum Toxins without Reduced Non-Toxin Proteins |
US20080233152A1 (en) * | 2006-12-29 | 2008-09-25 | Revance Therapeutics, Inc. | Compositions and Methods of Topical Application and Transdermal Delivery of Botulinum Toxins Stabilized with Polypeptide Fragments Derived from HIV-TAT |
US20080226551A1 (en) * | 2006-12-29 | 2008-09-18 | Revance Therapeutics, Inc. | Transport Molecules Using Reverse Sequence HIV-TAT Polypeptides |
US20100093639A1 (en) * | 2006-12-29 | 2010-04-15 | Revance Therapeutics, Inc. | Transport Molecules Using Reverse Sequence HIV-TAT Polypeptides |
US20100124559A1 (en) * | 2008-11-20 | 2010-05-20 | Allergan, Inc. | Early Treatment and Prevention of Increased Muscle Tonicity |
US9950042B2 (en) | 2008-12-04 | 2018-04-24 | Revance Therapeutics, Inc. | Extended length botulinum toxin formulation for human or mammalian use |
US10857215B2 (en) | 2012-04-12 | 2020-12-08 | Revance Therapeutics, Inc. | Use of botulinum toxin for the treatment of cerebrovascular disease, renovascular and retinovascular circulatory beds |
US9901627B2 (en) | 2014-07-18 | 2018-02-27 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
US11484580B2 (en) | 2014-07-18 | 2022-11-01 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
WO2022075785A1 (en) * | 2020-10-07 | 2022-04-14 | 주식회사 프로톡스 | Vacuum drying method for botulinum toxin |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6395277B1 (en) | Method and compositions for the treatment of cerebral palsy | |
US6939852B2 (en) | Methods and compositions for the treatment of cerebral palsy | |
US7384918B2 (en) | Botulinum toxin for treating muscle contracture | |
ES2329232T3 (en) | TREATMENT OF NEUROMUSCULAR DISORDERS AND AFFECTIONS WITH A DIFFERENT BOTULINIC SEROTYPE. | |
ES2347384T3 (en) | NEUROTOXIC COMPONENT OF A BOTULINIC TOXIN TO TREAT LATE DYSCINESIA. | |
EP0702559B1 (en) | Multiple botulinum toxins for treating neuromuscular disorders and conditions | |
US20210299213A1 (en) | Treatment of lower limb spasticity | |
ES2354166T3 (en) | USE OF BOTULINUM TOXIN TO TREAT MIOFASCIAL PAIN. | |
KR20240032688A (en) | Botulinum toxin formulations with reduced tolerance and methods relating thereto |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: ALLERGAN, INC., CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:MERZ PHARMA GMBH & CO. KGAA;MERZ PHARMACEUTICALS GMBH;REEL/FRAME:019831/0865 Effective date: 20070831 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- AFTER EXAMINER'S ANSWER OR BOARD OF APPEALS DECISION |