CA2510058A1 - Improved pharmaceutical botulinum toxin compositions - Google Patents
Improved pharmaceutical botulinum toxin compositions Download PDFInfo
- Publication number
- CA2510058A1 CA2510058A1 CA002510058A CA2510058A CA2510058A1 CA 2510058 A1 CA2510058 A1 CA 2510058A1 CA 002510058 A CA002510058 A CA 002510058A CA 2510058 A CA2510058 A CA 2510058A CA 2510058 A1 CA2510058 A1 CA 2510058A1
- Authority
- CA
- Canada
- Prior art keywords
- composition
- botulinum toxin
- units
- albumin
- sequestration agent
- 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.)
- Granted
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- 239000000203 mixture Substances 0.000 title claims abstract 55
- 108030001720 Bontoxilysin Proteins 0.000 title claims abstract 42
- 229940053031 botulinum toxin Drugs 0.000 title claims abstract 41
- 239000003795 chemical substances by application Substances 0.000 claims abstract 28
- 238000000034 method Methods 0.000 claims abstract 28
- 230000009919 sequestration Effects 0.000 claims abstract 28
- 108010088751 Albumins Proteins 0.000 claims abstract 22
- 102000009027 Albumins Human genes 0.000 claims abstract 22
- 208000018360 neuromuscular disease Diseases 0.000 claims abstract 5
- 208000002193 Pain Diseases 0.000 claims abstract 2
- 150000001720 carbohydrates Chemical class 0.000 claims abstract 2
- 235000014633 carbohydrates Nutrition 0.000 claims abstract 2
- 150000002632 lipids Chemical class 0.000 claims abstract 2
- 102000004169 proteins and genes Human genes 0.000 claims abstract 2
- 108090000623 proteins and genes Proteins 0.000 claims abstract 2
- 206010020852 Hypertonia Diseases 0.000 claims 4
- 208000012661 Dyskinesia Diseases 0.000 claims 3
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 claims 3
- 206010044074 Torticollis Diseases 0.000 claims 2
- 108010057266 Type A Botulinum Toxins Proteins 0.000 claims 2
- 206010005159 blepharospasm Diseases 0.000 claims 2
- 230000000744 blepharospasm Effects 0.000 claims 2
- 229940094657 botulinum toxin type a Drugs 0.000 claims 2
- 208000018197 inherited torticollis Diseases 0.000 claims 2
- 239000004005 microsphere Substances 0.000 claims 2
- 239000002245 particle Substances 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical group CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 claims 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical group CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 claims 1
- 229930182837 (R)-adrenaline Natural products 0.000 claims 1
- 208000008035 Back Pain Diseases 0.000 claims 1
- 241000193155 Clostridium botulinum Species 0.000 claims 1
- 102000008186 Collagen Human genes 0.000 claims 1
- 108010035532 Collagen Proteins 0.000 claims 1
- 208000027109 Headache disease Diseases 0.000 claims 1
- 208000019695 Migraine disease Diseases 0.000 claims 1
- 208000031481 Pathologic Constriction Diseases 0.000 claims 1
- 208000005392 Spasm Diseases 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 230000004075 alteration Effects 0.000 claims 1
- 230000002917 arthritic effect Effects 0.000 claims 1
- 229920001436 collagen Polymers 0.000 claims 1
- 239000002537 cosmetic Substances 0.000 claims 1
- 230000002638 denervation Effects 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 229960005139 epinephrine Drugs 0.000 claims 1
- 230000001815 facial effect Effects 0.000 claims 1
- 238000004108 freeze drying Methods 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 229940014041 hyaluronate Drugs 0.000 claims 1
- 230000004968 inflammatory condition Effects 0.000 claims 1
- 206010027599 migraine Diseases 0.000 claims 1
- 208000004296 neuralgia Diseases 0.000 claims 1
- 208000021722 neuropathic pain Diseases 0.000 claims 1
- 108010074523 rimabotulinumtoxinB Proteins 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 230000037303 wrinkles Effects 0.000 claims 1
- 150000003751 zinc Chemical class 0.000 claims 1
- 239000011701 zinc Substances 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 abstract 3
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 230000007012 clinical effect Effects 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 210000005036 nerve Anatomy 0.000 abstract 1
- 230000001537 neural effect Effects 0.000 abstract 1
- 210000000715 neuromuscular junction Anatomy 0.000 abstract 1
- 231100000614 poison Toxicity 0.000 abstract 1
- 239000002574 poison Substances 0.000 abstract 1
- 230000009885 systemic effect Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 239000003053 toxin Substances 0.000 abstract 1
- 231100000765 toxin Toxicity 0.000 abstract 1
- 108700012359 toxins Proteins 0.000 abstract 1
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
Abstract
Botulinum toxin, a well know systemic poison, produces favorable therapeutic effect by virtue of regionally attaching to nerves within the myoneural junction and possibly other tissues in a target region of a particular tissu e. The present invention provides compositions of botulinum toxin and a sequestration agent that increase sequestration and delivery of the botulinu m toxin to neural and associated tissues, as compared with available formulations of botulinum toxins, and thereby produce a beneficial clinical effect. The sequestration agents of the present invention include proteins, lipids and carbohydrates. A preferred composition of the present invention comprises a botulinum toxin and an albumin. The present invention also provides methods of treating neuromuscular diseases and pain using the disclosed compositions and methods of making the disclosed compositions.</SD OAB>
Claims (60)
1. A composition comprising botulinum toxin and a sequestration agent, wherein the sequestration agent is present in an amount between 550 and 550,000 µg sequestration agent per 100 LD50 units botulinum toxin.
2. The composition of claim 1, wherein the sequestration agent is present in an amount between 550 and 5,500 µg sequestration agent per 100 LD50 units botulinum toxin.
3. The composition of claim 1, wherein the sequestration agent is present in an amount between 5,500 and 13,000 µg sequestration agent per 100 LD50 units botulinum toxin.
4. The composition of claim 1, wherein the sequestration agent is present in an amount between 13,000 and 50,500 µg sequestration agent per 100 LD50 units botulinum toxin.
5. The composition of claim 1, wherein the sequestration agent is present in an amount between 50,500 and 505,000 µg sequestration agent per 100 LD50 units botulinum toxin.
6. The composition of claim 1, wherein the sequestration agent is formulated as encapsulated microspheres in an amount between 50,500 and 90,500 µg sequestration agent per 100 LD50 units botulinum toxin.
7. The composition of claim 1, wherein the botulinum toxin is selected from the group consisting of: botulinum toxin types A, B, C, D, E, F and G.
8. The composition of claim 7, wherein the botulinum toxin is botulinum toxin type A
from Hall strain Clostridium botulinum.
from Hall strain Clostridium botulinum.
9. The composition of claim 1, wherein the botulinum toxin comprises fractionated-light-chain botulinum toxin.
10. The composition of claim 1, wherein the botulinum toxin consists essentially of fractionated light chain botulinum toxin.
11. The composition of claim 1, wherein the botulinum toxin consists essentially of a mixture of hybrid and chain-translocated forms of botulinum toxin.
12. The composition of claim 1, wherein the botulinum toxin consists essentially of chimeric forms of botulinum toxin.
13. The composition of claim 1, wherein the botulinum toxin has a specific activity greater than or equal to 20 LD50 units per nanogram botulinum toxin.
14. The composition of claim 1, wherein the ratio of LD50 units of botulinum toxin to µg sequestration agent is less than or equal to 0.2 for botulinum toxin type A.
15. The composition of claim 1 wherein the ratio of LD50 units of botulinum toxin to µg sequestration agent is less than or equal to 10 for botulinum toxin type B.
16. The composition of claim 1 further comprising a pharmaceutically acceptable carrier.
17. The composition of claim 1, wherein the botulinum toxin is noncovalently bound to the asequestration agent.
18. The composition of claim 1, wherein the botulinum toxin is covalently bound to the sequestration agent.
19. A composition of claim 1 further comprising zinc or a zinc salt.
20. The composition of claim 1, wherein the sequestration agent is albumin.
21. The composition of claim 1, wherein albumin is present in an amount between 550 and 5,500 µg albumin per 100 LD50 units botulinum toxin.
22. The composition of claim 1, wherein albumin is present in an amount between 5,500 and 13,000 µg albumin per 100 LD50 units botulinum toxin.
23. The composition of claim 1, wherein albumin is present in an amount between 13,000 and 50,500 µg albumin per 100 LD50 units botulinum toxin.
24. The composition of claim 1, wherein albumin is present in an amount between 50,500 and 505,000 µg albumin per 100 LD50 units botulinum toxin.
25. The composition of claim 1, wherein albumin is formulated as encapsulated microspheres in an amount between 50,500 and 90,500 µg albumin per 100 LD50 units botulinum toxin.
26. The composition of claim 1, wherein the albumin is formulated as a solid albumin particle.
27. The composition of claim 1, wherein the albumin is recombinantly produced.
28. The composition of claim 20 further comprising one or more additional sequestration agents.
29. The composition of claim 1, wherein the sequestration agent is selected from the group consisting of: proteins, lipids and carbohydrates.
30. The composition of claim 29, wherein the sequestration agent is collagen.
31. The composition of claim 29, wherein the sequestration agent is hyaluronate.
32. The composition of claim 29, wherein the sequestration agent is epinephrine.
33. A method of localized denervation in a subject in need thereof, comprising administering an effective amount of the composition of claim 1.
34. The method of claim 33, wherein the subject suffers from a neuromuscular disease associated with increased muscle tone or involuntary movement.
35. The method of claim 34, wherein the neuromuscular disease associated with increased muscle tone with involuntary. movement is blepharospasm or torticollis.
36. The method of claim 35, wherein the neuromuscular disease associated with increased muscle tone with involuntary movement is blepharospasm.
37. The method of claim 36, wherein the effective amount is between 10-200 LD50 units.
38. The method of claim 35, wherein the neuromuscular disease associated with increased muscle tone with involuntary movement is torticollis.
39. The method of claim 38, wherein the effective amount is between 10 and units.
40. A method of treating a condition selected from the group consisting of facial wrinkles, rhytides and cosmetic alteration of lip and brow, in a subject in need thereof, comprising administering an effective amount of the composition of claim 1.
41. The method of claim 40, wherein the effective amount is between 2.5 and units.
42. A method of treating human headache disorders in a subject in need thereof, comprising administering an effective amount of the composition of claim 1.
43. The method of claim 42, wherein the effective amount is between 5 and 1,000 LD50 units.
44. A method of treating human migraine headache disorders in a subject in need thereof, comprising administering an effective amount of the composition of claim 1.
45. The method of claim 44, wherein the effective amount is between 5 and 1,000 LD50 units.
46. A method of treating human inflammatory conditions in a subject in need thereof, comprising administering an effective amount of the composition of claim 1.
47. The method of claim 46, wherein the effective amount is between 5 and 4,000 LD50 units.
48. A method of treating myopathic or neuropathic pain in a subject in need thereof, comprising administering an effective amount of the composition of claim 1.
49. The method of claim 48, wherein the effective amount is between 5 and 4,000 LD50 units.
50. A method of treating back pain or arthritic pain in a subject in need thereof, comprising administering an effective amount of the composition of claim 1.
51. The method of claim 50, wherein the effective amount is between 5 and 4,000 LD50 units.
52. A method of treating gastrointestinal spasm and strictures in a subject in need thereof, comprising administering an effective amount of the composition of claim 1.
53. The method of claim 52, wherein the effective amount is between 5 and 4,000 LD50 units.
54. A method of treating a hyperhyrosis syndrome in a subject in need thereof, comprising administering of the composition of claim 1.
55. The method of claim 54, wherein the effective amount is between 5 and 4,000 LD50 units.
56. A method of producing the composition of claim 1, comprising mixing albumin to botulinum toxin in a weight to weight ratio which exceeds 100 µg albumin to 1 ng of botulinum toxin.
57. A method of producing the composition of claim 1, comprising freeze drying or flash drying a mixture of a botulinum toxin and albumin in a weight to weight ratio of 100 µg albumin to 1 ng of botulinum toxin.
58. A method of producing the composition of claim 1, comprising lyophilizing a mixture of a botulinum toxin and albumin in a weight to weight ratio of 100 µg to 1 ng of botulinum toxin.
59. A composition comprising botulinum toxin and a sequestration agent, wherein the sequestration agent is present in an amount between 550 and 900,500 µg sequestration agent per 100 LD50 units botulinum toxin.
60. The composition of claim 59, wherein the albumin is formulated as a solid albumin particle.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US43590102P | 2002-12-20 | 2002-12-20 | |
US60/435,901 | 2002-12-20 | ||
PCT/IB2003/006145 WO2004060384A2 (en) | 2002-12-20 | 2003-12-22 | Pharmaceutical botulinum toxin compositions |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2510058A1 true CA2510058A1 (en) | 2004-07-22 |
CA2510058C CA2510058C (en) | 2010-03-16 |
Family
ID=32713047
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2510058A Expired - Lifetime CA2510058C (en) | 2002-12-20 | 2003-12-22 | Improved pharmaceutical botulinum toxin compositions |
Country Status (17)
Country | Link |
---|---|
US (2) | US7491403B2 (en) |
EP (1) | EP1594523B1 (en) |
JP (1) | JP2006519761A (en) |
KR (1) | KR20050094817A (en) |
CN (1) | CN100525831C (en) |
AT (1) | ATE426408T1 (en) |
AU (2) | AU2003300666A1 (en) |
BR (1) | BR0316871A (en) |
CA (1) | CA2510058C (en) |
CR (1) | CR9813A (en) |
DE (1) | DE60326887D1 (en) |
IL (1) | IL168745A0 (en) |
MX (1) | MXPA05006690A (en) |
NO (1) | NO20053424L (en) |
NZ (1) | NZ540425A (en) |
WO (1) | WO2004060384A2 (en) |
ZA (1) | ZA200504982B (en) |
Families Citing this family (60)
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US7780967B2 (en) * | 2000-02-08 | 2010-08-24 | Allergan, Inc. | Reduced toxicity Clostridial toxin pharmaceutical compositions |
US7763663B2 (en) * | 2001-12-19 | 2010-07-27 | University Of Massachusetts | Polysaccharide-containing block copolymer particles and uses thereof |
US7459164B2 (en) | 2002-05-28 | 2008-12-02 | Botulinum Toxin Research Associates, Inc. | Composition for therapeutic and cosmetic botulinum toxin |
US7691394B2 (en) * | 2002-05-28 | 2010-04-06 | Botulinum Toxin Research Associates, Inc. | High-potency botulinum toxin formulations |
DE60326887D1 (en) * | 2002-12-20 | 2009-05-07 | Botulinum Toxin Res Ass Inc | PHARMACEUTICAL COMPOSITIONS CONTAINING BOTULINUM TOXIN AND HUMAN SERUM ALBUMIN |
EP1599220B1 (en) * | 2003-03-06 | 2013-07-17 | Botulinum Toxin Research Associates, Inc. | Selection of patients with increased responsiveness to botulinum toxin |
US20040226556A1 (en) | 2003-05-13 | 2004-11-18 | Deem Mark E. | Apparatus for treating asthma using neurotoxin |
US7270826B2 (en) | 2004-01-05 | 2007-09-18 | Borodic Gary E | Methods of using Botulinum toxin for the treatment of hypervolemic lip deformity (lip ectropion) |
US9211248B2 (en) | 2004-03-03 | 2015-12-15 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
KR100852822B1 (en) * | 2004-07-26 | 2008-08-18 | 메르츠 파마 게엠베하 운트 코. 카가아 | Therapeutic composition with a botulinum neurotoxin |
US20060073208A1 (en) | 2004-10-01 | 2006-04-06 | Allergan, Inc. | Cosmetic neurotoxin compositions and methods |
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2003
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- 2003-12-22 EP EP03814518A patent/EP1594523B1/en not_active Revoked
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- 2003-12-22 KR KR1020057011339A patent/KR20050094817A/en not_active Application Discontinuation
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CN1729011A (en) | 2006-02-01 |
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JP2006519761A (en) | 2006-08-31 |
EP1594523A2 (en) | 2005-11-16 |
ZA200504982B (en) | 2007-05-30 |
IL168745A0 (en) | 2011-12-01 |
WO2004060384A2 (en) | 2004-07-22 |
AU2003300666A1 (en) | 2004-07-29 |
US20110293663A1 (en) | 2011-12-01 |
EP1594523B1 (en) | 2009-03-25 |
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CR9813A (en) | 2008-07-29 |
US20040151741A1 (en) | 2004-08-05 |
NZ540425A (en) | 2009-03-31 |
BR0316871A (en) | 2005-10-18 |
AU2010202062A1 (en) | 2010-06-10 |
CN100525831C (en) | 2009-08-12 |
NO20053424L (en) | 2005-09-16 |
WO2004060384A3 (en) | 2004-10-07 |
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