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US20030100574A1 - Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm-related clinical pathologies - Google Patents

Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm-related clinical pathologies Download PDF

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Publication number
US20030100574A1
US20030100574A1 US10/294,288 US29428802A US2003100574A1 US 20030100574 A1 US20030100574 A1 US 20030100574A1 US 29428802 A US29428802 A US 29428802A US 2003100574 A1 US2003100574 A1 US 2003100574A1
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United States
Prior art keywords
gonyautoxin
composition
mixture
saxitoxin
muscle
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Abandoned
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US10/294,288
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English (en)
Inventor
Nestor Wilson
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Phytotox SA
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Phytotox SA
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Publication date
Application filed by Phytotox SA filed Critical Phytotox SA
Assigned to PHYTOTOX S.A. reassignment PHYTOTOX S.A. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WILSON, NESTOR ANTONIO LAGOS
Publication of US20030100574A1 publication Critical patent/US20030100574A1/en
Priority to US11/338,156 priority Critical patent/US20060122200A1/en
Priority to US13/487,722 priority patent/US9301958B2/en
Priority to US14/043,634 priority patent/US8889681B2/en
Priority to US14/249,914 priority patent/US8871763B2/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • 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
    • 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
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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]

Definitions

  • This invention relates to pharmaceutical compositions containing heterocyclic guanidine-type compounds and uses thereof for blocking neuronal transmission. More specifically, this invention relates to tricyclic 3,4-propinoperhydropurines and uses thereof for blocking neuronal transmission.
  • Botulin A toxin is a neurotoxin that acts by chemiodenervation, or blocking the presynaptic release of the neurotransmitter acetylcholine in the neuromuscular plate, thus interfering with neuromuscular transmission, paralysing the muscle and preventing its contraction for a period of up to 4 months. Applied locally in the face of people, its effect is a facial rejuvenation that appears within 7-10 days after the toxin is applied, and has a duration of approximately 4 months. Botulin A toxin has been used for the treatment of diseases associated with muscular spasm, focal dystonia, sphincter relaxation (achalasia and anal fissure), hyperhydrosis and urinary bladder relaxation.
  • Botulin A toxin While Botulin A toxin is effective as a facial rejuvenate, it is an enzyme that is inherently unstable. This instability makes its use and handling complicated and less desirable. In fact, it requires freezing before using and must be used within four hours of opening the container. Because it is an enzyme, Botulin A toxin also generates antibodies that prevent its use in consecutive injections and can also induce an allergic response. In addition, its results are delayed 7-10 days, which is undesirable for patients wanting an immediate result. Accordingly, a need exists for a facial rejuvenate that is stable, fast-acting and that is not an enzyme.
  • compositions for interfering with neuronal transmission comprising an effective amount of at least one tricyclic 3,4-propinoperhydropurine are provided.
  • preparations for facial rejuvenation comprise an effective amount of the composition of the invention and a facial cream.
  • FIG. 1 is an illustration of an application pattern for the treatment of a human face.
  • compositions comprising heterocyclic guanidine-type compounds, and more specifically tricyclic 3,4-propinoperhydropurines, can be used for many cosmetic or clinical applications, without any surgery, side effects, allergies, immune rejection or hematoma.
  • the compositions of the invention may be used to treat conditions including, but not limited to blepharospasm, strabismus, focal dystonia, sphinceter relaxation (achalasia and anal fissure), hyperhydrosis, urinary bladder relaxation, muscular spasm-related pain management, muscular spasms, improved wound healing and facial wrinkling.
  • muscular relaxation is immediate, usually occurring in less than five minutes.
  • compositions of the invention comprise an effective amount of at least one tricyclic 3,4-propinoperhydropurine represented by the following structure:
  • R 1 and R 5 are independently H or OH; R 2 and R 3 are independently H or OSO 3 ; and R 4 is independently COONH 2 , OH, H, COONHSO 3 or COOCH 3 ; and a pharmacologically acceptable carrier.
  • These tricyclic 3,4-propinoperhydropurines may be purified from dinoflagellates, cyanobacterias and also may be accumulated by highly contaminated mollusks, which are also temporary muscular relaxants when locally injected. Any pharmacologically acceptable carrier may be used, including but not limited to water.
  • the compounds of the invention are generally diluted in a solution of acetic acid or 0.09% sodium chloride.
  • an effective amount is that amount sufficient to interfere with neuronal transmission by blocking the presynaptic release of the neurotransmitter acetylcholine in the neuromuscular plate, thus interfering with transmission, paralysing the muscle and preventing it from contracting, or producing a relaxation of contracted muscles.
  • an effective amount of the compositions of the invention may be a 100 to 800 microliter dose of forty units per milliliter solution of tricyclic 3,4-propinoperhydropurines.
  • the unit of activity is the amount of the composition of the invention necessary to block the muscular contractions of the crural biceps of a mouse leg for 1.5 to 2.0 hours.
  • the compounds of the invention are generally diluted with a 10 mM (millimolar), pH 4 solution of acetic acid.
  • the compositions of the invention comprise 40 units per milliliter of a 10 mM, pH 4 solution of acetic acid.
  • the pharmaceutical compositions of the invention comprise Saxitoxin.
  • the pharmaceutical compositions of the invention comprise Gonyautoxin 2.
  • the pharmaceutical compositions of the invention comprise Gonyautoxin 3.
  • the pharmaceutical compositions of the invention comprise Gonyautoxin 4.
  • the pharmaceutical compositions of the invention comprise Gonyautoxin 5.
  • the pharmaceutical compositions of the invention comprise neoSaxtoxin.
  • the pharmaceutical compositions of the invention comprise Gonyautoxin 1.
  • the pharmaceutical compositions of the invention comprise Decarbamoyl-Saxitoxin.
  • TABLE 1 Tricyclic 3,4-propinoperhydropurines Compound R 1 R 2 R 3 R 4 R 5 Saxitoxin H H H COONH 2 OH neoSaxitoxin OH H H COONH 2 OH Decarbamoyl- OH H H OH OH Saxitoxin Gonyautoxin OH H OSO ⁇ 3 COONH 2 OH 1 Gonyautoxin H H OSO ⁇ 3 COONH 2 OH 2 Gonyautoxin H OSO ⁇ 3 H COONH 2 OH 3 Gonyautoxin OH OSO ⁇ 3 H COONH 2 OH 4 Gonyautoxin H H H COONHSO ⁇ 3 OH 5
  • the pharmaceutical compositions comprise a mixture of tricyclic 3,4-propinoperhydropurines.
  • the compounds are purified and used individually and/or mixed together.
  • the pharmaceutical compositions of the invention comprise a mixture of Gonyautoxin 2, Gonyautoxin 3, and Saxitoxin.
  • the pharmaceutical compositions of the invention comprise a mixture of Gonyautoxin 4, Gonyautoxin 1, Gonyautoxin 5, Gonyautoxin 3 and Gonyautoxin 2.
  • the pharmaceutical compositions of the invention comprise neoSaxitoxin and Gonyautoxin 2.
  • compositions of the invention comprise a mixture of Saxitoxin, neoSaxitoxin, Decarbamoyl-Saxitoxin, Gonyautoxin 3 and Gonyautoxin 2. It should be understood by those of skill in the art that other mixtures and combinations of tricyclic 3,4-propinoperhydropurines are within the scope of this invention.
  • the compounds of the invention are used in combination with an effective amount of Botulin A toxin.
  • the pharmaceutical compositions of the invention comprise an effective amount of Botulin A toxin and an effective amount of at least one tricyclic 3,4-propinoperhydropurine.
  • the combination may be used in any cosmetic or clinical application in which the compounds of the invention, or Botulin A toxin are used, for example, blepharospasm, strabismus, focal dystonia, sphincter relaxation (achalasia and anal fissure), hyperhydrosis, urinary bladder relaxation, muscular spasm-related pain management, muscular spasms, improved wound healing, and facial wrinkle removal.
  • compositions of the invention may be used for many cosmetic and clinical applications including, but not limited to blepharospasm, strabismus, focal dystonia, sphincter relaxation (achalasia and anal fissure), hyperhydrosis, urinary bladder relaxation, muscular spasm-related pain management, muscular spasms, improved wound healing, and facial wrinkle removal.
  • the pharmaceutical compositions of the invention are applied locally in the form of preparations.
  • an effective amount of the pharmaceutical compositions of the invention are added to a facial cream complete with its coadjuvants.
  • these preparations are stable at room temperature, do not require refrigeration, are sterilizable, do not generate antibodies, are not peptide in nature, act immediately, and may be injected repeatedly without any side effects.
  • these compounds when applied locally, these compounds carry out their antispasmodic action by blocking the spreading of nervous impulse, or neuronal transmission, by reversibly binding to the sole biological molecular receptor, i.e. the voltage gated sodium channel, present in all neurons and excitable cells. By binding to this channel, there is no entry of sodium to the neuronal cell; depolarization does not occur and, therefore, propagation of the impulse is stopped.
  • This action mechanism blocks the presynaptic release of the neurotransmitter acetylcholine in the neuromuscular plate, thus interfering with neuromuscular transmission, paralysing the muscle and preventing it from contracting, or producing a relaxation of muscles contracted by pathological problems.
  • This mechanism is particularly efficient for cosmetic purposes, as it does not let some facial muscles contract, all of them associated with and responsible for the formation of wrinkles, thus producing the sought-after effect of facial rejuvenation.
  • the pharmaceutical preparations of the invention are applied locally around the muscle that is to be paralysed or prevented from contracting.
  • the application should be in amounts of no more than one milliliter in different places around the muscle, particularly around the areas of greatest innervations.
  • the unit of activity is the amount of the compositions of the invention necessary to block the contractions of the crural biceps of a mouse leg for 1.5 to 2 hours.
  • the preferred dosage rate is 100 to 800 microliters per injected point, depending on the size, irrigation and anatomical location of the muscle, while maintaining a concentration of 20-40 units/milliliter.
  • the effect is immediately apparent, generally occuring a maximum of thirty seconds after injection. The maximum effect may be seen within 15 minutes.
  • the injection may be accomplished by using a 1 milliliter, tuberculin-type disposable syringe with a twenty-seven to thirty gauge needle. In the case of strabismus, a dose of twenty to forty units in a volume of 50-100 microliters may be injected in the orbicular muscle.
  • Use of the pharmaceutical preparations of the invention is limited to individuals over twelve years old. There is no contraindication for pregnant women.
  • a photographic record is made of the person to be treated, first with her face resting and relaxed, and then, frowning and producing a maximum facial contraction. The person then places ice on their forehead and on the two lateral zones where the preparation is to be injected. With reference to FIG. 2, the application should follow a specific pattern.
  • a volume is injected alongside each black-dot injection point shown in FIG. 2.
  • a pharmaceutical composition comprising a (2:1:1 volume/volume) mixture of Gonyautoxin 2, Gonyautoxin 3 and Saxitoxin mixture is applied at a dose of 40 units/milliliter. Each injection is, made with a 1 milliliter, tuberculin-type disposable syringe with a 27-30 gauge needle. After injecting, the point of injection is disinfected with a gauze soaked in bi-alcohol or in any other disinfectant. The total amount required to complete the face treatment is 1.7 milliliters.
  • the expected result is an immediate inability to frown and to show lines when the face is resting.
  • the person experiences a feeling of facial stretching similar to that felt when applying a facial cream mask.
  • ice is applied on the injected zones for five minutes.
  • the patient gets used to the feeling of facial stretching.
  • the person walks out with no discernible wrinkles, a rejuvenated facial look, no face marks or hematoma, and completely normal.
  • the face recovers its normal color within twenty minutes, depending on how relaxed the injected patient has become.
  • the whole application procedure takes ten minutes at the most, and produces a very slight pain from the needle and the injected solution. The pain disappears as soon as the syringe is withdrawn.
  • the patient may be checked the next day and every fifteen days thereafter. At this dose, the effect lasts for one month. After the first month, the treatment may be repeated as often as necessary.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
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  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Dermatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Cosmetics (AREA)
US10/294,288 2001-11-15 2002-11-14 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm-related clinical pathologies Abandoned US20030100574A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US11/338,156 US20060122200A1 (en) 2001-11-15 2006-01-24 Use and application of a pharmaceutical composition containing a mixture of natural- origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm- related clinical pathologies
US13/487,722 US9301958B2 (en) 2001-11-15 2012-06-04 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine
US14/043,634 US8889681B2 (en) 2001-11-15 2013-10-01 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm-related clinical pathologies
US14/249,914 US8871763B2 (en) 2001-11-15 2014-04-10 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm- related clinical pathologies

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CL27642001 2001-11-15
CL2764-2001 2001-11-15

Related Child Applications (1)

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US11/338,156 Division US20060122200A1 (en) 2001-11-15 2006-01-24 Use and application of a pharmaceutical composition containing a mixture of natural- origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm- related clinical pathologies

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US20030100574A1 true US20030100574A1 (en) 2003-05-29

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Family Applications (5)

Application Number Title Priority Date Filing Date
US10/294,288 Abandoned US20030100574A1 (en) 2001-11-15 2002-11-14 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm-related clinical pathologies
US11/338,156 Abandoned US20060122200A1 (en) 2001-11-15 2006-01-24 Use and application of a pharmaceutical composition containing a mixture of natural- origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm- related clinical pathologies
US13/487,722 Expired - Fee Related US9301958B2 (en) 2001-11-15 2012-06-04 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine
US14/043,634 Expired - Fee Related US8889681B2 (en) 2001-11-15 2013-10-01 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm-related clinical pathologies
US14/249,914 Expired - Fee Related US8871763B2 (en) 2001-11-15 2014-04-10 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm- related clinical pathologies

Family Applications After (4)

Application Number Title Priority Date Filing Date
US11/338,156 Abandoned US20060122200A1 (en) 2001-11-15 2006-01-24 Use and application of a pharmaceutical composition containing a mixture of natural- origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm- related clinical pathologies
US13/487,722 Expired - Fee Related US9301958B2 (en) 2001-11-15 2012-06-04 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine
US14/043,634 Expired - Fee Related US8889681B2 (en) 2001-11-15 2013-10-01 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm-related clinical pathologies
US14/249,914 Expired - Fee Related US8871763B2 (en) 2001-11-15 2014-04-10 Use and application of a pharmaceutical composition containing a mixture of natural-origin heterocyclical guanidine, for cosmetology, wound healing, focal dystonia and muscular spasm- related clinical pathologies

Country Status (18)

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US (5) US20030100574A1 (fr)
EP (1) EP1443932B1 (fr)
JP (2) JP5331959B2 (fr)
KR (2) KR20100135884A (fr)
CN (2) CN1585642A (fr)
AU (1) AU2002348370B8 (fr)
BR (1) BR0214126A (fr)
CA (1) CA2466697C (fr)
EA (1) EA006739B1 (fr)
ES (1) ES2401570T3 (fr)
HU (1) HUP0402268A2 (fr)
IL (1) IL161949A0 (fr)
MX (1) MXPA04004543A (fr)
NO (1) NO20042475L (fr)
NZ (1) NZ533309A (fr)
PL (1) PL370686A1 (fr)
WO (1) WO2003047589A1 (fr)
ZA (1) ZA200403765B (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005110418A2 (fr) 2004-05-07 2005-11-24 Phytotox Limited Administration transdermique de phycotoxines
WO2005110275A1 (fr) 2004-05-07 2005-11-24 Phytotox Limited Methodes de traitement des plaies avec les gonyautoxines
WO2006119499A3 (fr) * 2005-05-05 2006-12-28 Phytotox Ltd Utilisation de phytotoxines pour applications veterinaires
WO2010109386A1 (fr) * 2009-03-24 2010-09-30 Proteus S.A. Procédé de purification industrielle de phycotoxines biologiquement actives
WO2011098539A1 (fr) * 2010-02-10 2011-08-18 Phytotox Limited Traitement de la perte du sens du toucher avec des dérivés de saxitoxine
US10920256B2 (en) 2016-02-12 2021-02-16 Vestlandets Innovasjonsseiskap AS Process

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20100135884A (ko) * 2001-11-15 2010-12-27 마이크로 알제 코포레이션 3, 4-프로피온퍼하이드로퓨린을 포함하는 약학 조성물 및 상기 조성물을 이용한 신경 전달의 블로킹 방법
JP2009177044A (ja) * 2008-01-28 2009-08-06 Panasonic Corp 電気ヒューズ回路
CA2760946C (fr) * 2009-05-07 2019-06-25 The Board Of Trustees Of The Leland Stanford Junior University Procedes et compositions pour etudier, visualiser par imagerie et traiter la douleur
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EP1802250A1 (fr) * 2004-05-07 2007-07-04 Phytotox Limited Methodes de traitement des plaies avec les gonyautoxines
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CA2466697C (fr) 2013-09-24
EA006739B1 (ru) 2006-04-28
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US9301958B2 (en) 2016-04-05
HUP0402268A2 (hu) 2005-02-28
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CA2466697A1 (fr) 2003-06-12
US20120238592A1 (en) 2012-09-20
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AU2002348370B8 (en) 2008-05-01
EP1443932B1 (fr) 2012-12-26
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US8889681B2 (en) 2014-11-18
WO2003047589A1 (fr) 2003-06-12
US20140221407A1 (en) 2014-08-07
JP5331959B2 (ja) 2013-10-30
US20060122200A1 (en) 2006-06-08
US20140163051A1 (en) 2014-06-12
US8871763B2 (en) 2014-10-28
EP1443932A4 (fr) 2007-11-28
JP2011068649A (ja) 2011-04-07
AU2002348370A1 (en) 2003-06-17
CN102349914A (zh) 2012-02-15
IL161949A0 (en) 2005-11-20
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