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WO1994020115A2 - Acide hyaluronique utilise comme traitement contre le cancer - Google Patents

Acide hyaluronique utilise comme traitement contre le cancer Download PDF

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Publication number
WO1994020115A2
WO1994020115A2 PCT/US1994/002506 US9402506W WO9420115A2 WO 1994020115 A2 WO1994020115 A2 WO 1994020115A2 US 9402506 W US9402506 W US 9402506W WO 9420115 A2 WO9420115 A2 WO 9420115A2
Authority
WO
WIPO (PCT)
Prior art keywords
hyaluronic acid
dog
acid
preparation
tumor
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.)
Ceased
Application number
PCT/US1994/002506
Other languages
English (en)
Other versions
WO1994020115A3 (fr
Inventor
Karen K. Brown
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Corp
Original Assignee
Miles Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Miles Inc filed Critical Miles Inc
Priority to AU63625/94A priority Critical patent/AU6362594A/en
Publication of WO1994020115A2 publication Critical patent/WO1994020115A2/fr
Publication of WO1994020115A3 publication Critical patent/WO1994020115A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters

Definitions

  • Hyaluronic acid is a high molecular weight mucopolysaccharide which can be obtained from numerous sources (e.g. rooster combs, umbilical cords, skin, artificial fluids, and certain bacteria such as Streptococci) . All sources appear to produce the same molecule composed of polymers of n-acetylglucosamine and glucuronic acid. The only variation appears to be the molecular weight which can range from less than 100,000 to greater than 1,000,000. Most hyaluronic acid has a molecular weight of greater than 700,000.
  • Hyaluronic acid has been used therapeutically for a number of years as a replacement for the vitreous humor of the eye post eye surgery, and, more recently, as replacement for joint fluid in arthritic joints.
  • An extensive discussion of its various utilities is found in U.S. Pat. No. 4,141,973 to Balazs. The mode of action for the joint usage has been accepted as that of lubrication.
  • hyaluronic acid Since the 1970's, hyaluronic acid has been known for its moisturizing effect when placed onto the skin.
  • cosmetic preparations containing hyaluronic acid These always describe the mucopolysaccharide as a moisturizer which remains on the surface of the skin and which is generally mixed with other moisturizers, emolients, creams, or humectants to form a cosmetic to moisturize the skin.
  • Some of these patents even describe a preparation containing hyaluronic acid which is claimed to reduce wrinkles: U.S. Pat. Nos. 5,055,298; 4,900,550; 4,973,473; 4,839,162; and 4,826,828.
  • Such preparations are complex mixtures of moisturizers, humectants, softeners and cell-penetrating components such as protectants and sealers.
  • Hyaluronic acid is considered as a secondary moisturizer in this set of qualifiers.
  • hyaluronic acid is characterized as being pharmaceutically pure (pure enough for drug use) and of low viscosity for safety and injectibility. Any source hyaluronic acid is acceptable. HA with a molecular weight as determined by FPLC or HPLC as low as 100,000 kd has been used.
  • the preparation is administered intramuscularly but may be as effective when administered intravenously or subcutaneously.
  • Hyaluronic acid as extracted and purified from various sources, occurs typically in a molecular weight range of greater than 1 x IO 6 as measured by Fast Protein Liquid Chromatography (FPLC) .
  • FPLC Fast Protein Liquid Chromatography
  • Some producers of HA sell a dried preparation which is obtained as a dry powder.
  • Other producers provide HA as sterile liquid concentrates. Any type of HA preparation may be used as long a ⁇ it is pure enough for pharmaceutical use.
  • Hyaluronic acid from any source may also be used for the formulations claimed.
  • a powdered form of HA is used, an amount equivalent to 1 weight percent (wt/vol) is added to water for injection.
  • wt/vol weight percent
  • the viscosity of this preparation is reduced to less than 50 centistrokes per second (c/s) at 37°C, as measured by a Cannon-Manning Semi-micro viscometer.
  • the procedure for reduction of viscosity without dramatically reducing the molecular weight involves: 1) adjusting the pH to approximately 10 and 2) mixing this high pH solution at 37°C for 24 to 48 hours or until the viscosity is adequately reduced.
  • liquid concentrate hyaluronic acid is used for the formulation the viscosity is reduced using an identical procedure once the liquid is prepared as a 1% solution. If the liquid concentrate hyaluronic acid has a viscosity less than 50 c/s at 37°C the viscosity reduction step is by-passed.
  • hyaluronic acid After reduction of viscosity lipoteichoic acid is added if required and the pH of the hyaluronic acid mixture is lowered to less than 5.0. Lipoteichoic acid must be pure and of the highest quality.
  • the preparation is filtered through a protein-binding filter of a porosity of 0.2u or less. The pH is aseptically adjusted to between 6.8 and 7.5 with sodium hydroxide. After filtration, the 1% HA preparation is evaluated for hyaluronic acid concentration, protein content, and nucleic acid content. A UV spectrophotometer is used.
  • the analysis of the preparations must indicate that the HA is at least 1 wt % when measured against a standard which has been evaluated for HA concentration by at least one other method (preferably FPLC or HPLC) .
  • the protein concentration is determined by the optical density at 280 nm.
  • the protein content as measured by this method must be less that 5 mg/mL.
  • the nucleic acid concentration as measured by this method must be less that 10 ug/ L.
  • a 9-year old soft-coated wheaton terrier dog developed a suspicious tumor on the eyelid of the right eye.
  • This tumor was black (same color as the lid) with ragged edges. It was about the size of a pea. Since the owner is the inventor of this patent, a preparation of 1% hyaluronic acid plus 10 ug/ml of lipoteichoic acid was tried prior to any other treatment.
  • the dog was injected intramuscularly with 1.0 mL of the preparation. Within 24 hours the tumor appeared smaller. By 72 hours the tumor was almost gone. By 96 hours the only way one could detect the tumor was by careful palpitation. This effect lasted approximately one month.
  • the dog Upon enlargement of the tumor once again, the dog was taken to a veterinarian for a diagnosis.
  • the tumor was biopsied and determined to be a melanoma.
  • the prognosis was not good.
  • the location and length of time of involvement indicated that the brain might be involved.
  • the veterinarian estimated that the dog would probably survive only "a few months”.
  • the dog was again injected with the preparation described above. Again, the tumor essentially disappeared.
  • the dog was observed closely and was given a 1.0 mL injection on a once-monthly basis. Each time the injection was administered the tumor essentially disappeared only to return approximately 20-30 days later.
  • Four months after the initial treatment the dog began suffering seizures similar to Grand Mai epileptic seizures.
  • the veterinarian's diagnosis was melanoma metastasis to the brain.
  • a four-year old boxer dog began scratching uncontrollably.
  • the owner took the dog to her veterinarian who conducted a series of tests including analyses for allergies.
  • the veterinarian noticed multiple nodules within the der is, some of which were ulcerated. Further evaluation indicated that the nodules were mast-cell tumors which had metastasised to the draining lymph nodes. The prognosis was poor.
  • the dog was not expected to live two months.
  • the owner was given medication to calm the dog and keep it from scratching. This medication, however, caused the dog to sleep all the time.
  • the inventor of this patent gave the individual a preparation containing 1% hyaluronic acid and 10 ug/ml of lipoteichoic acid to try. The owner injected it as often as necessary (1.0 mL intramuscularly up to 3 times per day) .
  • the owner discontinued the use of the tranquilizer obtained from her veterinarian.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Préparations à base d'acide hyaluronique, qui soignent le cancer. Lesdites préparations peuvent contenir d'autres ingrédients tels que de l'acide lipotéichoïque et sont injectées de manière parentérale ou directement dans la tumeur. Toutes les préparations peuvent être utilisées de façon répétée sans effets secondaires toxiques.
PCT/US1994/002506 1993-03-10 1994-03-08 Acide hyaluronique utilise comme traitement contre le cancer Ceased WO1994020115A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU63625/94A AU6362594A (en) 1993-03-10 1994-03-08 Hyaluronic acid used as a cancer treatment

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2895793A 1993-03-10 1993-03-10
US08/028,957 1993-03-10

Publications (2)

Publication Number Publication Date
WO1994020115A2 true WO1994020115A2 (fr) 1994-09-15
WO1994020115A3 WO1994020115A3 (fr) 1994-11-10

Family

ID=21846439

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/002506 Ceased WO1994020115A2 (fr) 1993-03-10 1994-03-08 Acide hyaluronique utilise comme traitement contre le cancer

Country Status (2)

Country Link
AU (1) AU6362594A (fr)
WO (1) WO1994020115A2 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996023896A1 (fr) * 1995-01-30 1996-08-08 Peter Truog Preparations antitumorales et anticholesterol contenant un acide lipoteichoique tire de streptococcus
WO1997021344A1 (fr) * 1995-12-13 1997-06-19 Sumitomo Pharmaceuticals Company, Limited Animal pathologique atteint de pleuresie
WO1997040841A1 (fr) * 1996-04-29 1997-11-06 Hyal Pharmaceutical Corporation Emploi de formes d'acide hyaluronique (ha) pour therapie anticancereuse
US5902795A (en) * 1992-06-16 1999-05-11 Trustees Of Tufts College Oligosaccharides reactive with hyaluronan-binding protein and their methods of use
WO2001047561A1 (fr) * 1999-12-28 2001-07-05 Bioniche Life Sciences Inc. L'acide hyaluronique dans le traitement du cancer
EP1260227A1 (fr) * 2001-05-23 2002-11-27 Societe Des Produits Nestle S.A. L'acide lipoteichoique des bacteries lactiques et son utilisation pour moduler des responses immunitaites induites par des bacteries a gram negatif, gram positif
US10219997B2 (en) * 2006-09-22 2019-03-05 Kochi University Radiation sensitizer or anti-cancer chemotherapy sensitizer
US12109232B2 (en) 2013-02-15 2024-10-08 Kortuc Inc. Radiation/chemotherapy sensitizer to be used for intratumoral local injection and for controlled release of hydrogen peroxide with hydrogel as carrier

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4678773A (en) * 1983-08-26 1987-07-07 Chugai Seiyaku Kabushiki Kaisha Antitumor agent
JPS6117A (ja) * 1984-06-11 1986-01-06 Seikagaku Kogyo Co Ltd ムコ多糖系癌転移抑制剤
US4725585A (en) * 1985-04-26 1988-02-16 Pharmacia Ab Method of enhancing the host defense
FR2584606A1 (fr) * 1985-07-12 1987-01-16 Dropic Utilisation de poly- et oligosaccharides pour l'obtention de medicaments actifs dans les pathologies du tissu conjonctif
DK505488D0 (da) * 1987-12-21 1988-09-09 Bar Shalom Daniel Middel og anvendelse af samme
JP2667441B2 (ja) * 1988-05-18 1997-10-27 生化学工業株式会社 血管内皮細胞増殖抑制剤

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5902795A (en) * 1992-06-16 1999-05-11 Trustees Of Tufts College Oligosaccharides reactive with hyaluronan-binding protein and their methods of use
WO1996023896A1 (fr) * 1995-01-30 1996-08-08 Peter Truog Preparations antitumorales et anticholesterol contenant un acide lipoteichoique tire de streptococcus
CN1113102C (zh) * 1995-01-30 2003-07-02 彼得·特鲁格 抗肿瘤制剂
WO1997021344A1 (fr) * 1995-12-13 1997-06-19 Sumitomo Pharmaceuticals Company, Limited Animal pathologique atteint de pleuresie
WO1997040841A1 (fr) * 1996-04-29 1997-11-06 Hyal Pharmaceutical Corporation Emploi de formes d'acide hyaluronique (ha) pour therapie anticancereuse
US7125858B2 (en) 1999-12-28 2006-10-24 Bioniche Life Sciences Inc. Hyaluronic acid in the treatment of cancer
WO2001047561A1 (fr) * 1999-12-28 2001-07-05 Bioniche Life Sciences Inc. L'acide hyaluronique dans le traitement du cancer
EP1250152B1 (fr) * 1999-12-28 2013-05-15 Bioniche Urology IP Inc. Composition synergique contenant de l'acide hyaluronique dans le traitement du cancer
WO2002094296A1 (fr) * 2001-05-23 2002-11-28 Societe Des Produits Nestle S.A. Acide lipoteichoique tire de bacteries d'acide lactique et son utilisation en tant que modulateur de reponses immunitaires induites par des bacteries gram-negatives, des bacteries gram-positives potentiellement pathogenes
US8329190B2 (en) 2001-05-23 2012-12-11 Societe Des Produits Nestle S.A. Lipoteichoic acid from lactic acid bacteria and its use to modulate immune responses mediated by gram-negative bacteria, potential pathogenic gram-positive bacteria
EP1260227A1 (fr) * 2001-05-23 2002-11-27 Societe Des Produits Nestle S.A. L'acide lipoteichoique des bacteries lactiques et son utilisation pour moduler des responses immunitaites induites par des bacteries a gram negatif, gram positif
US10219997B2 (en) * 2006-09-22 2019-03-05 Kochi University Radiation sensitizer or anti-cancer chemotherapy sensitizer
US12109232B2 (en) 2013-02-15 2024-10-08 Kortuc Inc. Radiation/chemotherapy sensitizer to be used for intratumoral local injection and for controlled release of hydrogen peroxide with hydrogel as carrier

Also Published As

Publication number Publication date
WO1994020115A3 (fr) 1994-11-10
AU6362594A (en) 1994-09-26

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