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WO1997040841A1 - Emploi de formes d'acide hyaluronique (ha) pour therapie anticancereuse - Google Patents

Emploi de formes d'acide hyaluronique (ha) pour therapie anticancereuse Download PDF

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Publication number
WO1997040841A1
WO1997040841A1 PCT/CA1997/000283 CA9700283W WO9740841A1 WO 1997040841 A1 WO1997040841 A1 WO 1997040841A1 CA 9700283 W CA9700283 W CA 9700283W WO 9740841 A1 WO9740841 A1 WO 9740841A1
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WO
WIPO (PCT)
Prior art keywords
hyaluronic acid
sodium hyaluronate
dosage
cancer
administration
Prior art date
Application number
PCT/CA1997/000283
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English (en)
Inventor
Rudolf Edgar Falk
Original Assignee
Hyal Pharmaceutical Corporation
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 Hyal Pharmaceutical Corporation filed Critical Hyal Pharmaceutical Corporation
Priority to AU25644/97A priority Critical patent/AU2564497A/en
Publication of WO1997040841A1 publication Critical patent/WO1997040841A1/fr

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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
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid

Definitions

  • This invention relates to the use of forms of hyaluronic acid for example, hyaluronic acid and pharmaceutically acceptable salts thereof such as sodium hyaluronate for the treatment of cancer.
  • hyaluronic acid for example, hyaluronic acid and pharmaceutically acceptable salts thereof such as sodium hyaluronate for the treatment of cancer.
  • BACKGROUND OF THE INVENTION Forms of hyaluronic acid have been disclosed for different purposes. In this regard, see, for example, United States Patent 4,141,973 and European Patent 0 197718B1.
  • Hyaluronic acid has been previously used for the transportation /delivery of medicines and therapeutic agents to sites in need of treatment in the body for the treatment of cancer (see International Publication WO 91/04058) which teaches as follows:
  • combinations and formulations for example an injectable formulation
  • a mammal for the treatment of a disease or condition
  • combinations or formulations employ or incorporate as the case may be a therapeutically effective non-toxic amount of a medicinal and /or therapeutic agent to treat the disease or condition (for example a free radical scavenger (for example ascorbic acid
  • Vitamin C for the treatment of mononucleosis
  • an anti-cancer agent e.g. chemotherapeutic agent
  • anti-viral agents for example a nonionic surfactant, e.g. nonoxynol-9 [nonylphenoxy polyethoxy ethanol] found in DelfenTM contraceptive cream, and anionic surfactants (e.g. cetyl pyridinium chloride) and cationic surfactants (e.g.
  • benzalkonium chloride non-steroidal anti-inflammatory drugs (NSAID) for example indomethacin, naproxen and (+/-) tromethamine salt of ketorolac (sold under the trademark ToradolTM) and steroidal anti-inflammatory drugs, anti-fungal agent, detoxifying agents (for example for administration rectally in an enema), analgesic, bronchodilator, anti-bacterial agent, antibiotics, drugs for the treatment of vascular ischemia (for example diabetes and Berger' s disease), anti-body monoclonal agent, minoxidil for topical application for hair growth, diuretics (for example furosemide (sold under the trademark LasixTM)), immunosuppressants (for example cyclosporins), lymphokynes (such as interleukin - 2 and the like), alpha- and- ⁇ -interferon and the like) administered with, or carried in, an amount of hyaluronic acid and /or salts thereof (for example the sodium salt) and
  • the formulation can be administered among other methods, intravenously, intra arterially, intraperitoneally, intrapleurally, transdermally, on the skin (topically), rectally, orally or by direct injection (for example into a tumor, into an abscess or similar disease focus) or put on a patch to be secured to the skin of the patient.
  • the hyaluronic acid and /or salts thereof and the agent can be administered separately but are administered in sufficient amounts and in an immediate time sequence or interval (preferably concurrently and more preferably simultaneously), preferably at the identical site (e.g. one given intravenously and the other "piggy backed"), to treat the disease or condition.”
  • hyaluronic acid and salts thereof and other forms with different chemicals and drugs alters their distribution and performance in the human body and produces an unusual targeting for underperf fused tissue and /or pathological tissue.
  • ascorbic acid Vitamin C
  • hyaluronic acid sodium hyaluronate
  • the hyaluronic acid enhances the anti-neoplastic activity and effect of the ascorbic acid.
  • NSAID for example indomethacin (dissolved in n-methyl glucamine) or other NSAID is administered with greater than 200mg hyaluronic acid for 1 - 2 mg/kg body weight of the NSAID (in one instance indomethacin and NMG)
  • no major toxic side effects occur such as gastro-intestinal distress, neurological abnormalities, depression, etc., even at elevated amounts of indomethacin (if necessary).
  • the amount of hyaluronic acid is decreased below that amount, the usual side effects may begin to reoccur.
  • the responses that have been observed are superior when the NSAID (for example IndocidTM) is combined with hyaluronic acid demonstrating clearly that the combination is now "targeting" to the pathological tissue even when administered by the systemic intravenous route.
  • neoplastic diseases when receiving in addition to other chemicals (for example ascorbic acid [Vitamin C], phloretin and anti-cancer drugs), 50 - 200 mg NSAID - hyaluronic acid (sodium hyaluronate) (for example indomethacin and hyaluronic acid) experience dramatic relief of pain immediately. This is followed within a short period of time by a resolution and resorbtion of neoplastic lesions with an improvement of pulmonary, and liver function if there is tumor present in these organs.
  • chemicals for example ascorbic acid [Vitamin C], phloretin and anti-cancer drugs
  • 50 - 200 mg NSAID - hyaluronic acid sodium hyaluronate
  • indomethacin and hyaluronic acid experience dramatic relief of pain immediately. This is followed within a short period of time by a resolution and resorbtion of neoplastic lesions with an improvement of
  • the dead tumor material and the debris and tumor toxins appear to be better eliminated by the body through the action of the macrophages whose activity is enhanced by the addition of the NSAID (or a steroidal anti- inflammatory drug) administered with hyaluronic acid (or salt or other form thereof).
  • the addition of the NSAID for example with hyaluronic acid (sodium hyaluronate) deblocks the macrophages by preventing enzymatic production of prostaglandin synthetase which blocks macrophage functioning.
  • the hyaluronic acid (and salt and other forms) not only enhance the activity of the NSAID but also reduce any side effects and toxicity that is associated with the use of the prostaglandin synthesis inhibitors.
  • agents suitable for use as chemotherapeutic agents are novantrone (Mitoxantrone), Methotrexate, 5-FU (5-Fluorouracil), carboplatinum, methyl CCNU administered orally and Mitomycin C.” (iv) at page 26, lines 32 to 37:
  • the hyaluronic acid and salts thereof may be utilized at varying doses - 10 to 1000 mg/70 kg person with the optimal doses tending to range between 50 and 350 mg/70 kg individual. As there is no toxicity, the hyaluronic acid can obviously be administered in a dose excess (for example 3000 mg/70 kg individual) without any adverse effects.” (v) and, at page 33, line 37 to page 35, line 30:
  • Cancer increasing activity free radical scavenger, of macrophages superoxide dismutase, ascorbic acid(Vitamin C) anti-cancer drugs, NSAID, Chemotherapeutic Agents, detoxifying Agents (e.g. cholestyramine)
  • nonionic surfactants e.g., shingles nonoxynol-9 and anionic, (e.g. cetyl pyridinium chloride) and cationic (e.g. benzalkonium chloride), surfactants
  • NSAID e.g. (toxins and debris), diclofenac, decreasing side effects, indomethacin, piroxicam, relief of pain (e.g. ibuprofen, tromethamine salt back pain) of Ketorolac, naproxen,
  • Bronchodilation bronchodilators e.g. beclo- methasone diproprionate (sodium cromogiycate although not specifically a broncho- dialator), theophylline
  • Vascular ischemia treat limbs in respect of diabetes, Berger's disease, etc with suitable medicine e.g. Trental
  • HIV DMSO
  • Vitamin C e.g. indomethacin, naproxen, ketorolac tromethamine
  • interferon VibramycinTM
  • doxcycline e.g. indomethacin, naproxen, ketorolac tromethamine
  • Blockers e.g. atenolol, propranolol
  • Hyaluronic acid has not been used for the treatment of cancer by itself.
  • Applicant is aware of International Publication No. WO 94/20115 (by Miles, Inc.) which purports to teach preparations containing hyaluronic acid for the treatment of cancer.
  • the hyaluronic acid preparations for the treatment of cancer include lipoteichoic acid. This is clear from the examples of treatment taught.
  • Example 1 a nine year old terrier dog was treated with dosages of 1% hyaluronic acid and lO ⁇ g/ml of lipoteichoic acid administered regularly until four months after treatment when the dog began suffering seizures from what the veterinarian diagnosed as melanoma metastasis to the brain.
  • Example 2 a four year old boxer dog was treated.
  • Hyaluronan Receptor RHAMM
  • H-ras Transformation proposes that hyaluronan may be used in certain neoplastic transformation situations to alter the function of abnormal cells.
  • cytotoxic agents are used to treat cancer
  • the use of cytotoxic agents and other agents subjects the patient to the effects of the cytotoxic agents in the body.
  • an NSAID agent with in excess of 200 mg./70 kg. person of hyaluronic acid (taught in WO 91/04058) causing the side effects normally accompanying the use of the NSAID, such as gastro ⁇ intestinal distress, neurological abnormalities, depression, etc., to disappear even at elevated amounts of the NSAID, the NSAID is still present.
  • a cytotoxic agent is present, even if the form of HA reduces the side effects of the cytotoxic agent's use the body is still subjected to the medicine.
  • cancer is a disease which weakens the body and its immune response, where possible, the additional medicines if not needed should be deleted so as not to overly tax the patient's bodily functions.
  • a novel process for the treatment of cancer comprising the oral or systemic (intravenous preferably) administration of a form of hyaluronic acid as the active agent selected from the group consisting of hyaluronic acid and pharmaceutical ⁇ acceptable salts thereof in amounts and over such period of time to permit the successful treatment of cancer - either remission or full elimination or, at least, until such time and for such duration to stop or reduce the growth of the cancer cells so that the patient's condition does not deteriorate further.
  • the administration is of hyaluronic acid as the active agent in a suitable diluent (such as saline or sterile water) without any further active agents to treat the cancer in amounts that are usually considered, by persons skilled in the art, larger amounts of hyaluronic acid in each dosage for example, exceeding 750 mg. per 70 kg. person and preferably, exceeding 1 g. per 70 kg. person for each dosage given.
  • a suitable diluent such as saline or sterile water
  • the dosages consist only of a form of hyaluronic acid for example, hyaluronic acid and /or a pharmaceutically acceptable form thereof (for example, sodium hyaluronate) as the active agent without any other active, in a diluent.
  • Hyaluronic acid in such amounts can also be, if preferable or desirable, administered with agents which detoxify the patient (see for example, WO91/04058 which teaches such detoxification and whose teachings are incorporated herein by reference) or the use of an NSAID for inhibiting prostaglandin synthesis if suitable or with a cytotoxic agent (chemotherapeutic agent) such as 5-FU (5-Fluorouracil).
  • chemotherapeutic agent chemotherapeutic agent
  • 5-FU 5-FU
  • a novel method for the treatment of cancer of a patient comprising administration of at least two courses of therapy, one course comprising administration of a form of hyaluronic acid as the active agent selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof as the active agent in amounts exceeding about 750 mg/70 kg person and preferably exceeding lgm/70 kg person for each dosage given, in a suitable diluent for a period of time for the patient to be effected thereby (for example, the patient receiving such amounts over such a period of time for remission or reduction, of the cancer, and thereafter after a further period of time, administering another course of therapy (stage of therapy) comprising the administration of dosages to the patient, each dosage comprising an effective dosage amount of a cytotherapy (chemotherapy such as 5-FU (5-Fluorouracil)) for a further period of time.
  • chemotherapy such as 5-FU (5-Fluorouracil
  • the period between the one stage (course) of therapy (administration of dosages of hyaluronic acid as the only active agent in a diluent) and the second stage (course) (administration of the course of therapy of dosages, each dosage comprising an effective dosage amount of chemotherapy (for example, 5-FU (5-Fluorouracil)) can be in the order of 6-9 weeks.
  • the patient may be given dosage amounts of chemotherapy first (for example, the usual dosage amounts of chemotherapy such as 5-FU (5- Fluorouracil)) for a specified period of time followed by the period when nothing is administered (for example 6-9 weeks) then followed by the course of therapy of the forms of hyaluronic acid in the amounts and for such period of time suitable for such treatment.
  • chemotherapy for example, the usual dosage amounts of chemotherapy such as 5-FU (5- Fluorouracil)
  • 5-FU 5-FU
  • a novel method of treatment comprising administering orally and /or systemically at least a two-stage course of cancer treatment, one of the courses comprising administering orally or systemically effective dosage amounts of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof as an active therapeutic agent in a suitable diluent over a suitable time period and, another course of therapy comprising administering orally or systemically effective dosage amounts of a chemotherapeutic agent (anti ⁇ cancer agent) over a suitable time period wherein a time period (rest period) of no administration of either course is provided between the stoppage of the administration of one of the courses of administration and the beginning of the other (for example second) course of administration.
  • a chemotherapeutic agent anti ⁇ cancer agent
  • the said method comprises the course of administration comprising the form of hyaluronic acid being administered before the course comprising the chemotherapeutic agent.
  • the said method comprises the course of administration comprising the chemotherapeutic agent being administered before the course of administration comprising the form of hyaluronic acid.
  • the period of time between the end of the administration of one course of cancer treatment (hyaluronic acid and cytotherapy) and the commencement of another course of cancer treatment (the other of cytotherapy and hyaluronic acid) is between about 6-9 weeks.
  • 3000 mg. or more of the form of hyaluronic acid may be even given patients in each dosage for the treatment without adverse effect for example, upon either oral or intravenous administration of the form of hyaluronic acid.
  • the effective dose may vary with the route of administration and with the tumor type, location, and the bulk and activity of the tumor.
  • hyaluronic acid and/or pharmaceutically acceptable salts thereof also suitable for use with Applicant's invention is an amount having the following specifications / characteristics:
  • Another such form of hyaluronic acid may comprise:
  • Another such amount is available from Hyal Pharmaceutical Corporation and comes in a 15 ml vial of Sodium hyaluronate 20mg/ml (300mg/vial - Lot 2F3).
  • the sodium hyaluronate amount is a 2% solution with a mean average molecular weight of about 225,000 daltons.
  • the amount also contains water q.s. which is triple distilled and sterile in accordance with the U.S. P. for injection formulations.
  • the vials of hyaluronic acid and/or salts thereof may be carried in a Type 1 borosilicate glass vial closed by a butyl stopper which does not react with the contents of the vial.
  • the amount of hyaluronic acid and /or salts thereof may also comprise the following characteristics: a purified, substantially pyrogen-free amount of hyaluronic acid obtained from a natural source having at least one characteristic selected from the group (and preferably all characteristics) consisting of the following: i) a molecular weight within the range of 150,000-225,000; ii) less than about 1.25% sulphated mucopolysaccharides on a total weight basis; iii) less than about 0.6% protein on a total weight basis; iv) less than about 150 ppm iron on a total weight basis; v) less than about 15 ppm lead on a total weight basis; vi) less than 0.0025% glucosamine; vii) less than 0.025% glucuronic acid; viii) less than 0.025% N-acetylglucosamine; ix) less than 0.0025% amino acids; x) a UV extinction coefficient at 257 nm
  • the hyaluronic acid is mixed with sterile water and the amount of hyaluronic acid has a mean average molecular weight within the range of 150,000- 225,000 daltons. More preferably, the amount of hyaluronic acid comprises at least one characteristic selected from the group (and preferably all characteristics) consisting of the following characteristics: i) less than about 1% sulphated mucopolysaccharides on a total weight basis; ii) less than about 0.4% protein on a total weight basis; iii) less than about 100 ppm iron on a total weight basis; iv) less than about 10 ppm lead on a total weight basis; v) less than 0.00166% glucosamine; vi) less than 0.0166% glucuronic acid; vii) less than 0.0166% N-acetylglucosamine; viii) less than 0.00166% amino acids; x) a UV extinction coefficient at 257 nm of less than about
  • UV/Vis Scan 190-820nm Matches reference scan OD, 260nm ⁇ 0.25 OD units
  • Hyaluronan HA-M5070 Another amount of sodium hyaluronate proposed to be used is sold under the name Hyaluronan HA-M5070 by Skymart Enterprises, Inc. having the following specifications:
  • hyaluronic acid and /or its salts may be chosen from other suppliers and those described in prior art documents provided they are suitable.
  • Canadian Letters Patent 1,205,031 (which refers to United States Patent 4,141,973 as prior art) refers to hyaluronic acid fractions having average molecular weights of from 50,000 to 100,000; 250,000 to 350,000; and 500,000 to 730,000 and discusses processes of their manufacture.
  • hyaluronic acid or salts
  • it may have to be diluted to permit administration and ensure no coagulation or blockage. It may also have to autoclaved to reduce the molecular weight for successful administration.
  • the form of hyaluronic acid may be administered in doses in excess of 40 mg/kg, for example, 3000 mg/70 kg person or greater without adverse toxic effects.
  • a novel method of treatment of patients with cancer may now consist of administering an effective amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof, such as sodium hyaluronate, all having a molecular weight of less than 750,000 daltons in a suitable diluent (sterile water or saline) for such period of time as required.
  • a suitable diluent sterile water or saline
  • the treatments may provide periods where the treatments are weekly for a number of months, decreasing or increasing as required, adjusting each dosage up or down as required as to the amount of the form of hyaluronic acid (hyaluronan).
  • hyaluronic acid selected from hyaluronic acid and pharmaceutically acceptable salts thereof (sodium hyaluronate) is provided for the treatment of cancer wherein the form of hyaluronic acid is the active component.
  • a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof, for example, sodium hyaluronate
  • the form of hyaluronic acid is the active component for treating cancer and exceeds about 750 mg. per 70 kg. person and preferably, exceeds 1 g. of the form of hyaluronic acid per 70 kg. person per dosage in a pharmaceutically acceptable diluent such as sterile water or saline.
  • This patient was diagnosed with cancer of the rectum.
  • This patient was first seen with wide spread metastatic cancer of the breast in May 1995. She had been initially diagnosed with breast cancer and treated for local disease. She subsequently developed metastases approximately 4 years from diagnosis. When first assessed at our clinic, the patient had wide spread metastases, including lung, liver, bone, local and cutaneous recurrence. Based on the laboratory measurement assessment that her platelets were low (40,000 per unit assessment), it was the opinion of three clinical consultants that she had bone marrow involvement.
  • This patient was diagnosed with metastatic gastric cancer - adenocarcinoma type November 30th, 1995. She was subsequently operated on and had a laparotomy done which showed diffuse metastatic cancer involving the stomach and other abdominal organs. This was biopsied. A gastrotomy tube was placed to decompress the stomach as it was anticipated the patient would within the near future, develop gastric obstruction which would necessitate decompression.
  • oral HA hyaluronic acid
  • body weight 70 kg
  • the patient continues on oral and intravenous hyaluronan.
  • This patient represents a case of diffuse and metastatic adenocarcinoma of the stomach in the abdomen with initially a projected survival time of 1-3 months. Currently, she would appear to be in complete remission.
  • This patient had a carcinoma of the breast resected in October 1992 with reconstructive surgery. There was lymph node involvement. She was treated at another centre throughout this and was placed in a randomized study series but apparently drew a no-treatment arm and did not have any treatment. She then developed multiple liver metastases. Her estrogen and progesterone receptors were both positive suggesting a hormone sensitive tumor.
  • the patient has always determined her own therapy and the timing of any intervention and has not been treated. She was re-assessed in mid- April, 1996 and is clinically in complete remission.
  • This patient was diagnosed with poorly differentiated adenocarcinoma - giant cell component of the lung on September 5th, 1995. He had his left lung resected. In the pathological specimen, it was noted that the tumor had extended through to the pleural lining of the lung and that all lymph nodes that were biopsied were positive for tumor. This is classified as a non-curative resection.
  • This patient illustrates a response to intravenous and oral HA, treated subsequently only with oral HA. It again indicates the frequency of dosing required orally to maintain a response.

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  • General Health & Medical Sciences (AREA)
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  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

L'invention a trait à une méthode thérapeutique anticancéreuse consistant à administrer, par voie orale ou par voie générale, intraveineuse de préférence, une quantité efficace d'une forme posologique d'acide hyaluronique choisi dans le groupe constitué par l'acide hyaluronique et ses sels, acceptables du point de vue pharmaceutique, comme seul agent thérapeutique, dans un diluant, selon des quantités appropriées et pendant un laps de temps suffisant pour permettre une fructueuse thérapie anticancéreuse.
PCT/CA1997/000283 1996-04-29 1997-04-28 Emploi de formes d'acide hyaluronique (ha) pour therapie anticancereuse WO1997040841A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU25644/97A AU2564497A (en) 1996-04-29 1997-04-28 Use of formes f hyaluronic acid (ha) for the treatment of cancer

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CA002175282A CA2175282A1 (fr) 1996-04-29 1996-04-29 Utilisation de diverses formes d'acide hyaluronique (ah) pour le traitement du cancer
CA2,175,282 1996-04-29

Publications (1)

Publication Number Publication Date
WO1997040841A1 true WO1997040841A1 (fr) 1997-11-06

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AR (1) AR006892A1 (fr)
AU (1) AU2564497A (fr)
CA (1) CA2175282A1 (fr)
WO (1) WO1997040841A1 (fr)
ZA (1) ZA973622B (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
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WO2000054762A3 (fr) * 1999-03-15 2001-03-08 Univ Boston Inhibition d'une angiogenese
GB2368525A (en) * 2000-07-14 2002-05-08 Meditech Res Ltd Hyaluronan as a cytotoxic agent, drug pre-sensitizer and chemo-sensitizer in the treatment of disease
WO2003018062A1 (fr) * 2001-08-27 2003-03-06 Meditech Research Limited Protocoles therapeutiques ameliores
AU760404B2 (en) * 2000-07-14 2003-05-15 Alchemia Oncology Pty Limited Hyaluronan as a cytotoxic agent, drug pre-sensitizer and chemo-sensitizer in the treatment of disease
US6911436B2 (en) * 1994-05-12 2005-06-28 Dermal Reserach Laboratories, Inc. Pharmaceutical composition of complex carbohydrates and essential oils and methods of using the same
AU2002325635B2 (en) * 2001-08-27 2007-04-05 Alchemia Oncology Pty Limited Improved therapeutic protocols
EP1311276A4 (fr) * 2000-07-31 2007-09-12 Dermal Res Lab Inc Procedes servant a prevenir ou a traiter des maladies et des etats au moyen de glucides complexes
EP2045270A2 (fr) 2002-10-18 2009-04-08 FIDIA FARMACEUTICI S.p.A. Taxanes à liaison covalente pour acide hyaluronique ou dérivés d'acide hyaluronique
US7879824B2 (en) 2001-07-31 2011-02-01 Dermal Research Laboratories, Inc. Methods of preventing or treating diseases and conditions using complex carbohydrates
US8003782B1 (en) 1999-02-01 2011-08-23 Dermal Research Laboratories, Inc. Pharmaceutical composition of complex carbohydrates and essential oils and methods of using the same
US8623354B2 (en) 2005-09-07 2014-01-07 Alchemia Oncology Pty Limited Therapeutic compositions comprising hyaluronan and therapeutic antibodies as well as methods of treatment
US8741970B2 (en) 1999-01-13 2014-06-03 Alchemia Oncology Pty Limited Composition and method for the enhancement of the efficacy of drugs
US20140271620A1 (en) * 2013-03-14 2014-09-18 National Cheng Kung University Modified hyaluronan and uses thereof in cancer treatment
US8937052B2 (en) 2005-07-27 2015-01-20 Alchemia Oncology Pty Limited Therapeutic protocols using hyaluronan
US9066919B2 (en) 2000-07-14 2015-06-30 Alchemia Oncology Pty Limited Hyaluronan as a chemo-sensitizer in the treatment of cancer
US11090330B2 (en) 2014-05-26 2021-08-17 Songyuan Chen Pharmaceutical solution having a toxicity-reducing effect for antitumor drugs, and pharmaceutical composition comprising same

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JPS6117A (ja) * 1984-06-11 1986-01-06 Seikagaku Kogyo Co Ltd ムコ多糖系癌転移抑制剤
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WO1995030423A2 (fr) * 1991-07-03 1995-11-16 Norpharmco Inc. Traitement du cancer et prevention des metastases

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JPS6117A (ja) * 1984-06-11 1986-01-06 Seikagaku Kogyo Co Ltd ムコ多糖系癌転移抑制剤
WO1992001003A1 (fr) * 1990-07-10 1992-01-23 Board Of Regents, The University Of Texas System Derives de glycosaminoglycan et leur emploi en tant qu'inhibiteurs d'invasion de tumeurs ou de profusion metastatique-ii
US5464942A (en) * 1990-07-24 1995-11-07 Seikagaku Kogyo Kabushiki Kaisha Phospholipid- or lipid-linked glycosaminoglycan and process for producing the same
WO1995030423A2 (fr) * 1991-07-03 1995-11-16 Norpharmco Inc. Traitement du cancer et prevention des metastases
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Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6911436B2 (en) * 1994-05-12 2005-06-28 Dermal Reserach Laboratories, Inc. Pharmaceutical composition of complex carbohydrates and essential oils and methods of using the same
US8741970B2 (en) 1999-01-13 2014-06-03 Alchemia Oncology Pty Limited Composition and method for the enhancement of the efficacy of drugs
US8003782B1 (en) 1999-02-01 2011-08-23 Dermal Research Laboratories, Inc. Pharmaceutical composition of complex carbohydrates and essential oils and methods of using the same
US9220290B2 (en) 1999-02-01 2015-12-29 Dermal Research Laboratories, Inc. Pharmaceutical composition of complex carbohydrates and essential oils and methods of using the same
US6472379B1 (en) 1999-03-15 2002-10-29 Trustees Of Boston University Angiogenesis inhibition
WO2000054762A3 (fr) * 1999-03-15 2001-03-08 Univ Boston Inhibition d'une angiogenese
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AU2564497A (en) 1997-11-19
ZA973622B (en) 1997-11-25
CA2175282A1 (fr) 1997-10-30
AR006892A1 (es) 1999-09-29

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