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WO1994008574A1 - Traitement de la cachexie et inhibition de l'activite de il-6 - Google Patents

Traitement de la cachexie et inhibition de l'activite de il-6 Download PDF

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Publication number
WO1994008574A1
WO1994008574A1 PCT/US1993/009527 US9309527W WO9408574A1 WO 1994008574 A1 WO1994008574 A1 WO 1994008574A1 US 9309527 W US9309527 W US 9309527W WO 9408574 A1 WO9408574 A1 WO 9408574A1
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Prior art keywords
cachexia
suramin
sulfate
result
infection
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Application number
PCT/US1993/009527
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English (en)
Inventor
Gideon Strassmann
Original Assignee
Otsuka America Pharmaceutical, 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
Priority to KR1020007015079A priority Critical patent/KR100360579B1/ko
Priority to KR1020007015080A priority patent/KR100344334B1/ko
Application filed by Otsuka America Pharmaceutical, Inc. filed Critical Otsuka America Pharmaceutical, Inc.
Priority to JP6510102A priority patent/JPH08502295A/ja
Priority to EP93923270A priority patent/EP0664700A1/fr
Priority to KR1019950701386A priority patent/KR950703336A/ko
Publication of WO1994008574A1 publication Critical patent/WO1994008574A1/fr

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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
    • A61K31/70—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
    • 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
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • 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
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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

Definitions

  • the present invention relates to a method for treating cachexia in a patient, particularly a human being, and a method for the inhibition of IL-6 activity.
  • Cachexia a potentially lethal syndrome afflicting mammals, frequently complicates the treatment of infection, inflammation and cancer. It is characterized by profound weight loss caused by wasting of body fat (adipose) and muscle (protein). Tracey et al., J. Ex . Med. , Vol. 167, 1211-1227 (Mar. 1988). Lawson et al. , Ann. Rev. Nutr. , 2:277-301 (1982). Anorexia, anemia, and weakness may also occur in cachexia. Tracey et al., supra. Cachexia may further be characterized by, inter alia, depression of glucose level (hypoglycemia) and elevation of triglyceride level (hypertriglyceridemia) .
  • Cachexia may result from diverse causes such as age, cancer, and infections by parasites and by microorganisms such as bacteria, fungi, viruses and protozoa. Both acute and chronic infections or illnesses frequently cause cachexia. In fact, most chronic, fatal, nonneoplastic diseases terminate in cachexia (e.g. chronic disseminated infections, or prolonged insufficiency of heart, lungs, liver, kidneys, or the small intestines). Lawson et al., Ann. Rev. Nutr. , 2:277-301 (1982). Moreover, the syndrome is not alleviated by adequate caloric uptake. Indeed, weight loss may continue in cachexia even while an adequate diet is consumed. Silva et al., J. General Microbiology. Vol. 134, 1629-1633 (1988).
  • TDM also known as cord factor (CF)
  • CF cord factor
  • TNF tumor necrosis factor
  • cachexia may be unrelated to tumor size or parasite load, and profound wasting has been observed in patients with tumor burdens of only 0.01 to 5.0% body mass. If not reversed, physiological changes associated with cachexia lead to immunological deficiencies, organ failure, and multiple metabolic abnormalities. Tracey et al. , J. Ex . Med. , 167, 1211-1227 (Mar. 1988). Theologides, Cancer, May Supplement, 43, 2004-2012 (1979). The physiological changes due to cachexia decrease the patient's tolerance to chemotherapy and radiation therapy, as well as increase the frequency of post-surgical complications. The nausea, vomiting, and anorexia induced by chemotherapeutic agents as well as radiation injury can be very severe. In addition, chemotherapy is a major factor in malnutrition. It is well recognized that therapy is often as debilitating as the cancer itself. The malnourished patient has a much narrower safe therapeutic margin for most oncologic therapy, van Eys, supra.
  • the present invention provides a method for treating cachexia, comprising the step of administering to a patient an amount of a sulfate-containing compound, such as suramin or a derivative thereof, effective for said treatment.
  • a sulfate-containing compound such as suramin or a derivative thereof
  • the invention contemplates treating all forms of cachexia, whether induced by infection, cancer, age or otherwise.
  • the present invention also provides a method for the inhibition of interleukin 6 ("IL-6") activity, comprising the step of administering to a patient an amount of a sulfate- containing compound, such as suramin or a derivative thereof, effective for said inhibition.
  • IL-6 interleukin 6
  • Figure 1 sets forth the time dependent inhibition of C- 26 cachexia with the use of suramin.
  • Figure 2 sets forth the lack of effect of suramin on tumor (C-26) growth in vivo.
  • Figure 3 sets forth the dose dependent inhibition of C- 26 cachexia with the use of suramin.
  • Figure 4 sets forth the prevention of turpentine-induced wasting with the use of suramin.
  • Figure 5 sets forth the inhibition of bioactivity of IL- 6 with the use of suramin.
  • Figure 6 sets forth the prevention of the binding of IL-6 to human myeloma cells with the use of suramin in a dose dependent manner.
  • the instant invention provides a method for treating cachexia resulting from infection, cancer, age or otherwise.
  • the claimed method can also be used to treat any of the symptoms associated with the cachexia syndrome.
  • the method of the instant invention may be employed to mitigate or completely eliminate weight loss due to wasting of body fat and muscle, hypertriglyceridemia, hypoglycemia, and anorexia.
  • the claimed invention may be used to prevent loss of tissue in vital organs.
  • the instant method is particularly useful in treating cachexia due to cancer or chronic infections.
  • the method of the instant invention may be used, for example, to treat cachexia arising as a result of infection, chronic or otherwise, caused by a unicellular or multicellular parasite, or microbe such as a bacteria, fungus, protozoa or virus, or a combination of these organisms.
  • the present invention contemplates treatment of cachexia due to: infections by gram-negative or gram-positive bacteria, such as gram-positive cocci (pneumococcal, staphylococcal and streptococcal infections) ,
  • enteric gram-negative bacilli coliform bacterial infections, typhoid fever, Salmonella infections, Shigella infections, cholera
  • spirochetal and rickettsial infections spirochetal and rickettsial infections, viral infections (influenza, hepatitis, Sendai, herpes), and
  • the method of the instant invention is also useful in treating cachexia resulting from cancer.
  • Treatment of cachexia resulting from either a TNF- or non-TNF-producing cancer is within the scope of the instant invention.
  • all forms of cachexia produced by carcinomas or leukemias are treatable by the instant method.
  • Treatment according to the claimed invention will mitigate or totally eliminate the symptoms of cachexia, such as wasting and other physiological changes. This treatment may allow the patient to better tolerate chemotherapy or radiation therapy, improving the patient's overall prognosis and quality of life.
  • IL-6 interleukin 6
  • IL-6 interleukin 6
  • the measurement of the bioactivity of IL-6 is known in the art and can be accomplished by a variety of methods including B-9 assay.
  • Cachexia is treated and the bioactivity of IL-6 is inhibited by the use of sulfate-containing compounds.
  • the sulfate-containing compounds to be used in the present invention can be any sulfate-containing compound which will inhibit the bioactivity of IL-6 and/or will be effective in the treatment of cachexia as described above.
  • sulfate-containing compound that is effective in the inhibition of IL-6 bioactivity and is also effective in the treatment of cachexia is suramin.
  • the suramin used in the present invention is also known as suramin sodium or 8-8'-[CarbonyIbis[imino-3,1- phenylenecarbonyl-imino(4-methyl-3,l- phenylene)carbonylimino] ]bis-l,3,5-naphtha-lenetrisulfonic acid hexasodiu salt.
  • Commercially available suramin is preferred and is known by the tradenames Bayer 205, 309F, Antrypol, Germanin, Moranyl, Naganol, Naganin, and Naphuride Sodium.
  • Derivatives of suramin can also be used in the present invention.
  • examples of such derivatives include, but are not limited to, the derivatives described in Baghdiguian et al., Cancer Letters, 60 (1991) pp. 213-219 which is incorporated herein by reference.
  • Other examples of effective sulfate- containing compounds include, but are not limited to, Pentosan polysulfate and Dextran sulfate or a combination of sulfate-containing compounds.
  • sulfate-containing compound for example, suramin or derivatives thereof, Dextran sulfate or Pentosan polysulfate, that provides the desired mitigation or total elimination of cachexia or the inhibition of IL-6 activity is contemplated within the present invention.
  • sulfate-containing compounds such as suramin or derivatives thereof, Dextran sulfate and Pentosan polysulfate
  • sulfate-containing compounds may be administered to patients in the commercially obtained form, or may be first formulated into pharmaceutical compositions comprising an effective amount of the sulfate-containing compound and one or more pharmacologically acceptable nontoxic carriers, diluents or adjuvants.
  • Such compositions are, for example, in the form of liquid preparations including solution, suspension, and emulsion preparations.
  • Such compositions may also be solid preparations given as is or reconstituted to a liquid for use by addition of a suitable carrier.
  • Pharmaceutical carriers may be sterile liquids, such as water and the like. Water is a preferred carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions may also be employed as liquid carriers, particularly for injectable solutions. Other suitable pharmaceutical excipients may be used. These compositions can take the form of solutions, suspensions, tablets, pills, capsules, powders, sustained-release formulations and the like. Suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences” by E.W. Martin.
  • Sulfate-containing compounds of the present invention may be administered in the appropriate form according to methods known to those skilled in the art, such as orally, intravenously, subcutaneously, intracutaneously or intramuscularly. Intravenously is the preferred method of administration.
  • sulfate- containing compounds of the present invention such as the suramin or derivatives thereof, according to the methods of the invention before, as well as after, the onset of cachexia or exposure to the factor giving rise to cachexia.
  • Dosages selected are those which mitigate or completely eliminate the symptoms associated with cachexia (e.g. weight loss) or dosages which inhibit IL-6 activity, which symptoms are familiar to those skilled in the art. Determination of the appropriate dosages for treatment are routinely made by those of ordinary skill in the art and are wirhin the array of tasks routinely performed by them without undue experimentation.
  • the amount of the sulfate-containing compound, such as suramin or derivatives thereof, to given in any form is not limited specifically, and can be .er- ined suitably according to the age and sex of the patient, the degree of disease, etc.
  • the sulfate-containing compound, for example, suramin or derivatives thereof may be administered, for example, at a dose of about 0.01 g to about 10 g per week, wherein a week is understood to be 5-7 days.
  • the dose may be given once per week or the dose may be divided and given daily, or the dose may be staggered throughout the week, e.g., biweekly, triweekly.
  • patient is used herein in its broadest sense to mean mammals, including humans, as well as other mammals such as farm and laboratory animals, for example, horses, cows, dogs, cats, guinea pigs, mice, and rats.
  • mice (CD)2F1 obtained from Charles Rivers Laboratories were weighed and then were inoculated with 0.5 X 10 C-26.IVX cells derived from the colon adenocarcinoma (by the procedure described in Strassmann et al., J. Clin. Invest. , 89, pp. 1681-84 (May 1992) which is incorporated herein by reference).
  • the day of inoculation was identified as day 0 (d0).
  • PBS phosphate buffered saline
  • mice On day 19, all the mice were sacrificed and the final total weight, the host weight, the tumor weight, epididymal fat, and dry weight were measured. Table 1 sets forth the results. As can be seen from the results, the average percent weight loss for the mice receiving suramin was 12.0 +/- 6.0% while with PBS alone the average percent weight loss of the mice was 30.5 +/- 4.8 %. Thus, suramin clearly prevented weight loss in comparison to control animals.
  • mice were Inoculated with 0.5x10" C-26.IVX cells on d 0. On d 7 and 13 mice received PBS or suramin I P. On d 19 mice were sacrificed and cachexia markers were measured. Results are expressed as mean iSD.
  • mice obtained from the same source as above were injected with 0.5 ml PBS intraperitoneally and eight other mice from the same source as above were injected with 100 mg/kg body weight of suramin intraperitoneally.
  • the injections were given on days 7 and 12.
  • the weight of the two groups was measured several times a week.
  • the suramin inhibited C- 26 mediated weight loss in a significant time dependent manner.
  • tumor volume was also measured and the results are set forth in Figure 2.
  • the suramin had no significant effect on the tumor (C-26) growth in-vivo except on day 19. This indicates that the treatment of the present invention affects the host directly.
  • EXAMPLE 3 EXAMPLE 3:
  • mice were obtained and injected with C-26 cells as set forth above for Example 1, and then were put into four groups of five mice each.
  • the mice were injected intraperitoneally with increasing amounts of suramin as indicated in Figure 3 except for the control mice.
  • the total weight of each group was compared to a control group of five mice which had been injected with 0.5 ml PBS intraperitoneally.
  • increasing concentrations of suramin resulted in decreased percentage of weight loss.
  • suramin inhibited wasting in a dose dependent manner.
  • Figure 4 sets forth results of treatment with suramin in the prevention of turpentine-induced wasting, an acute type of inflammation.
  • day -3 five male (CD)2F1 mice, obtained from Charles Rivers Laboratories, each received intraperitoneally 0.5 ml of PBS.
  • Five other mice obtained from the same source each received intraperitoneally 100 mg/kg body weight suramin diluted with 0.5 ml of PBS.
  • This experiment analyzed whether suramin inhibits IL-6 bioactivity by interfering with binding to the IL-6 receptor.
  • U266 indicator cells obtained from ATCC
  • a binding buffer made up of RPMI medium, 0.1 mg BSA and 25 uM Hepes, and 100,000 cpm (0.8 ng) of 125I-IL-6.
  • the tubes were divided into six groups of three tubes each and received suramin as follows: group 1 had
  • group 6 received excess unlabeled IL-6 without suramin for use in determining the background of binding in this assay. After 90 minutes of incubation at 4°C and the centrifugation of cells on oil (a standard radioreceptor assay) Strassmann, J. Immunol. , 147:1279-1289 (1991), the amount of radioactivity bound to the cells was determined. A can be seen in Figure 6, suramin prevents binding of the IL- to the U266 cells in a dose dependent manner.
  • mice received 5.0 mg/mouse of suramin intravenously and eight other mice received 0.2 ml PBS/mouse intravenously 0.5 hour. Thereafter, all sixteen o the mice received an injection of 300,000 cpm (2.4 ng) of
  • 125 I-IL-6 125 I-IL-6.
  • Four mice from each group were sacrificed 30 minutes after receiving the 125I-IL-6 and the remaining four mice from each group were sacrificed 60 minutes after receiving the 125I-IL-6.
  • the liver, kidney, and spleen were removed and measured for radioactivity (cpm).
  • cpm radioactivity
  • suramin injected mice had approximately 50% less radioactivity measured in the liver, indicating that suramin may prevent binding of radioactive IL-6 to the liver.
  • suramin may accelerate clearance of IL-6 from the body as indicated by the increase of radioactive IL-6 presen in the kidney.
  • IL-6 pathology for example, cachexia
  • Table 2 Modulation of 125I-IL-6 Sequestration by Suramin
  • Results are expressed as mean cpm + 0.5 range of 2 mice per point. Liver radioactivity is expressed as cpm/gm.
  • Example 5 The same procedures set forth in Example 5 was followed except that a different sulfate-containing compound, Pentosa polysulfate, was used. As set forth in Table 3, Pentosan polysulfate prevented the proliferation of B-9 cells in response to IL-6.
  • Pentosan polysulfate inhibits proliferation of B-9 cells in response to IL-6.
  • Example 6 The same procedure set forth in Example 6 was followed, except that Pentosan polysulfate was used instead of Suramin. As set forth in Table 4, increasing amounts of Pentosan polysulfate inhibited the binding of radioactive IL-6 to U266 human myeloma cells. Table 4: Pentosan polysulfate inhibits binding of radioactive IL-6 to U266 cells.
  • Example 5 The same procedure set forth in Example 5 was followed except in this example, Dextran sulfate and Dextran, were used instead of Suramin. As set forth in Table 5, Dextran sulfate prevented the proliferation of B-9 cells in response to IL-6. Also, as set forth in Table 5, Dextran did not prevent the proliferation of B-9 cells in response to IL-6. These combined results suggest that the sulfate in the Dextran sulfate is an active ingredient which prevented the proliferation of B-9 cells in response to IL-6. Table 5: Dextran sulfate but not dextran inhibit IL-6 dependent proliferation of B-9 cells.

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Abstract

L'invention concerne des procédés permettant de traiter la cachexie chez un patient et d'inhiber la bioactivité de IL-6. Ils consistent à administrer à un patient une quantité efficace d'un composé contenant du sulfate, par exemple la suramine, un dérivé de suramine, du polysulfate de pentosan, ou du sulfate de Dextran. L'invention est également efficace pour lutter contre les maladies associées à IL-6.
PCT/US1993/009527 1992-10-13 1993-10-12 Traitement de la cachexie et inhibition de l'activite de il-6 WO1994008574A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
KR1020007015079A KR100360579B1 (ko) 1992-12-21 1993-10-05 규소-탄소 중합체가 접착된 표면을 갖는 기판 적층물
KR1020007015080A KR100344334B1 (ko) 1992-12-21 1993-10-05 플라즈마 발생장치
JP6510102A JPH08502295A (ja) 1992-10-13 1993-10-12 悪液質の治療およびｉｌ−６活性の阻害
EP93923270A EP0664700A1 (fr) 1992-10-13 1993-10-12 Traitement de la cachexie et inhibition de l'activite de il-6
KR1019950701386A KR950703336A (ko) 1992-10-13 1993-10-12 악액질의 치료와 il-6 활성의 저해

Applications Claiming Priority (4)

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US95937192A 1992-10-13 1992-10-13
US13401993A 1993-10-08 1993-10-08
US08/134,019 1993-10-08
US07/959,371 1993-10-08

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JP (1) JPH08502295A (fr)
KR (1) KR950703336A (fr)
CA (1) CA2146988A1 (fr)
WO (1) WO1994008574A1 (fr)

Cited By (9)

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FR2808687A1 (fr) * 2000-04-27 2001-11-16 Goemar Lab Sa Medicament contenant des substances polysaccharidiques pour l'activation de l'apoptose
WO2002034292A1 (fr) * 2000-10-25 2002-05-02 Chugai Seiyaku Kabushiki Kaisha Agents preventifs ou therapeutiques contre le psoriasis renfermant l'antagoniste de l'il-6 comme substance active
EP0811384A4 (fr) * 1995-02-13 2002-09-18 Chugai Pharmaceutical Co Ltd Inhibiteur de decomposition des proteines musculaires contenant un anticorps du recepteur de l'interleukine-6
WO2002002189A3 (fr) * 2000-06-30 2002-09-19 Polydex Pharma Sulfate de cellulose et autres polysaccharides sulfates utilises dans la prevention ou le traitement de nombreuses infections, notamment l'infection par le virus du papillome
EP1557170A3 (fr) * 2000-06-30 2005-09-21 Polydex Pharmaceuticals Limited Sulfate de la cellulose et autres polysaccharides pour la prevention et traitment d'une infection par le virus du papillome et autres infections
EP1534303A4 (fr) * 2002-08-13 2008-03-19 Univ Monash Polymeres charges d'agents antimicrobiens presentant une resistance a la degradation lysosomiale lors de la filtration et du passage renaux, compositions et procede d'utilisation
WO2010016628A1 (fr) * 2008-08-04 2010-02-11 Sammy Opiyo Composés suramine-amino conjugués pour états médicaux
US9629856B2 (en) 2010-03-03 2017-04-25 Anteis Sa Compositions and methods for the treatment of skin diseases and disorders using antimicrobial peptide sequestering compounds
EP3402812B1 (fr) 2016-01-11 2024-03-27 Dignity Health Modulateurs des canaux cationiques activés par le zinc

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022114111A1 (fr) * 2020-11-27 2022-06-02 マルホ株式会社 Composition pharmaceutique ou cosmétique

Citations (1)

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EP0486809A2 (fr) * 1990-11-14 1992-05-27 FARMITALIA CARLO ERBA S.r.l. Utilisation de la suramine contre des maladies relatées au TNF

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EP0486809A2 (fr) * 1990-11-14 1992-05-27 FARMITALIA CARLO ERBA S.r.l. Utilisation de la suramine contre des maladies relatées au TNF

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Title
G. STRASSMANN ET AL.: "Suramin interferes with Interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo", J. CLIN. INVEST., vol. 92, no. 5, 1993, pages 2152 - 2159 *
R. SHIAO ET AL.: "Glucocorticoid and suramin inhibition of IL-6-stimulated immunoglobulin secretion in lymphoid tumor cells.", PROC. AM. ASSOC. CANCER RES. ANNU. MEET., vol. 32, no. 0, 1991, pages 55 *

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0811384A4 (fr) * 1995-02-13 2002-09-18 Chugai Pharmaceutical Co Ltd Inhibiteur de decomposition des proteines musculaires contenant un anticorps du recepteur de l'interleukine-6
WO2001080807A3 (fr) * 2000-04-27 2002-04-18 Goemar Lab Sa Medicament contenant des substances polysaccharidiques pour l'activation de l'apoptose
FR2808687A1 (fr) * 2000-04-27 2001-11-16 Goemar Lab Sa Medicament contenant des substances polysaccharidiques pour l'activation de l'apoptose
US7226914B2 (en) 2000-06-30 2007-06-05 Rush Presbyterian-St. Luke's Medical Center Cellulose sulfate and other sulfated polysaccharides to prevent and treat papilloma virus infection and other infections
US7235536B2 (en) 2000-06-30 2007-06-26 Rush Presbyterian-St. Luke's Medical Center Cellulose sulfate and other sulfated polysaccharides to prevent and treat papilloma virus infection and other infections
EP1557170A3 (fr) * 2000-06-30 2005-09-21 Polydex Pharmaceuticals Limited Sulfate de la cellulose et autres polysaccharides pour la prevention et traitment d'une infection par le virus du papillome et autres infections
EP1552823A3 (fr) * 2000-06-30 2005-09-21 Polydex Pharmaceuticals Limited Sulfate de la cellulose et autre polysaccharides pour la prevention et traitment d'une infection par le virus du papillome et autres infections
US7078392B2 (en) 2000-06-30 2006-07-18 Polydex Pharmaceuticals Limited Cellulose sulfate and other sulfated polysaccharides to prevent and treat papilloma virus infection and other infections
WO2002002189A3 (fr) * 2000-06-30 2002-09-19 Polydex Pharma Sulfate de cellulose et autres polysaccharides sulfates utilises dans la prevention ou le traitement de nombreuses infections, notamment l'infection par le virus du papillome
US7320792B2 (en) 2000-10-25 2008-01-22 Chugai Seiyaku Kabushiki Kaisha Preventives or remedies for psoriasis containing as the active ingredient IL-6 antagonist
WO2002034292A1 (fr) * 2000-10-25 2002-05-02 Chugai Seiyaku Kabushiki Kaisha Agents preventifs ou therapeutiques contre le psoriasis renfermant l'antagoniste de l'il-6 comme substance active
US8562990B2 (en) 2000-10-25 2013-10-22 Chugai Seiyaku Kabushiki Kaisha Method of treating psoriatic arthritis with an IL-6 receptor antibody
US8597644B2 (en) 2000-10-25 2013-12-03 Chugai Seiyaku Kabushiki Kaisha Method for treating psoriasis by administering an antibody to interleukin-6 receptor
EP1534303A4 (fr) * 2002-08-13 2008-03-19 Univ Monash Polymeres charges d'agents antimicrobiens presentant une resistance a la degradation lysosomiale lors de la filtration et du passage renaux, compositions et procede d'utilisation
WO2010016628A1 (fr) * 2008-08-04 2010-02-11 Sammy Opiyo Composés suramine-amino conjugués pour états médicaux
GB2474809A (en) * 2008-08-04 2011-04-27 Sammy Opiyo Conjugated suramin amino compounds for medical conditions
GB2474809B (en) * 2008-08-04 2013-03-13 Sammy Opiyo Suramin amino salts for medical conditions
US9629856B2 (en) 2010-03-03 2017-04-25 Anteis Sa Compositions and methods for the treatment of skin diseases and disorders using antimicrobial peptide sequestering compounds
EP3402812B1 (fr) 2016-01-11 2024-03-27 Dignity Health Modulateurs des canaux cationiques activés par le zinc

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KR950703336A (ko) 1995-09-20
JPH08502295A (ja) 1996-03-12
EP0664700A1 (fr) 1995-08-02

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