WO1998008532A1 - Methods of treating renal disease with a gastrin releasing peptide receptor antagonist - Google Patents
Methods of treating renal disease with a gastrin releasing peptide receptor antagonist Download PDFInfo
- Publication number
- WO1998008532A1 WO1998008532A1 PCT/US1997/015080 US9715080W WO9808532A1 WO 1998008532 A1 WO1998008532 A1 WO 1998008532A1 US 9715080 W US9715080 W US 9715080W WO 9808532 A1 WO9808532 A1 WO 9808532A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- receptor antagonist
- releasing peptide
- peptide receptor
- gastrin releasing
- renal disease
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- 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
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- This invention relates to a method of treating renal disease, preferably chronic renal disease, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a Gastrin Releasing Peptide Receptor (GRP-R) antagonist.
- GRP-R Gastrin Releasing Peptide Receptor
- GRP Gastrin releasing peptide
- GRP Val-Pro-Leu-Pro-Ala-Gly-Gly-Gly-Thr-Val-Leu-Thr-Lys-Met-Tyr-Pro-Arg-Gly- Asn-His-T -Ala-Val-Gly-His-Leu-Met-NH2- GRP is indicated as an autocrine factor in several types of cancer cells. Dietrich, J. B. Cell Mol. Bio. 40: 731 -746, (1994) and Cuttitta, F. et al.. Nature 316: 823-826, (1985). Specifically, GRP has been shown to stimulate proliferation of lung (Cuttitta, F. et al., Nature 316: 823- 826, (1985)), breast (Nelson, J.
- This invention relates to a method of treating renal disease, preferably chronic renal disease, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a Gastrin Releasing Peptide Receptor (GRP-R) antagonist.
- GRP-R Gastrin Releasing Peptide Receptor
- FIG. 1 depicts the competition of [1251] aGRP14-27 binding to rat mesangial cells by unlabeled GRP and NMB;
- FIG. 1 (bottom panel) depicts scatchard analysis of [1251] aGRP 14-27 binding to rat mesangial cells;
- FIG. 2 depicts the effect of GRP on (Ca++)i mobilization in rat mesangial cells
- FIG. 3 depicts the effect of GRP on mesangial cell proliferation
- FIG. 4 depicts the effect of GRP on TGF ⁇ l, fibronectin and osteopontin mRNA in mesangial cells.
- Gastrin Releasing Peptide Receptor antagonists and derivatives thereof, as used herein is meant an antibody, a peptide or a nonpeptide chemical compound which exhibits pharmaceutical activity by antagonizing the GRP Receptor.
- GRP Gastrin Releasing Peptide
- the filters were washed three times with buffer and counted in a gamma counter with an efficiency of 75%. Specific binding which was between 85-95% was calculated by subtracting non-specific binding from total binding. Competition binding experiments were performed by adding increasing concentrations of unlabeled ligands to membranes in the presence of indicated concentration of [** ⁇ I] Bombesin.
- Intracellular Calcium mobilization in response to GRP was determined by measuring the fluorescence of fura-2-loaded mesangial cells with a dual-wave length spectrofluorometer (University of Pennsylvania Biomedical Instruments Group) following the procedure of Albrightson et al. (1995).
- This invention discloses Gastrin Releasing Peptide Receptor antagonist and pharmaceutically acceptable salts or hydrates or solvates thereof as being useful for treating renal disease, preferably chronic renal disease, in mammals, including humans.
- a Gastrin Releasing Peptide Receptor antagonist or a pharmaceutically acceptable salt or hydrate or solvate thereof can be administered to a subject in a conventional dosage form prepared by combining a Gastrin Releasing Peptide Receptor antagonist or a pharmaceutically acceptable salt or hydrate or solvate thereof, with a conventional pharmaceutically acceptable carrier or diluent according to known techniques.
- a Gastrin Releasing Peptide Receptor antagonist or a pharmaceutically acceptable salt or hydrate or solvate thereof is administered to a mammal, including a human, in an amount sufficient to prevent or alleviate renal disease, preferably chronic renal disease.
- the route of administration of the Gastrin Releasing Peptide Receptor antagonist is not critical but is usually oral or parenteral, preferably oral.
- parenteral as used herein includes intravenous, intramuscular, subcutaneous, intranasal, intrarectal, transdermal, intravaginal or intraperitoneal administration.
- the subcutaneous and intramuscular forms of parenteral administration are generally preferred.
- the daily parenteral dosage regimen will preferably be from about 0.01 mg kg to about 50 mg/kg of total body weight, most preferably, from about 0.1 mg/kg to about 5 mg/kg.
- each parenteral dosage unit will contain the active ingredient in an amount of from about 0.5 mg to about 150 mg.
- the Gastrin Releasing Peptide Receptor antagonist which are active when given orally can be formulated as liquids, for example, syrups, suspensions or emulsions, tablets, capsules and lozenges.
- a liquid formulation will generally consist of a suspension or solution of the compound or pharmaceutically acceptable salt in a suitable liquid carrier(s) for example, ethanol, glycerine, non-aqueous solvent, for example polyethylene glycol, oils, or water with a suspending agent, preservative, flavoring or coloring agent.
- a composition in the form of a tablet can be prepared using any suitable pharmaceutical carrier(s) routinely used for preparing solid formulations. Examples of such carriers include magnesium stearate, starch, lactose, sucrose and cellulose.
- a composition in the form of a capsule can be prepared using routine encapsulation procedures.
- pellets containing the active ingredient can be prepared using standard carriers and then filled into a hard gelatin capsule; alternatively, a dispersion or suspension can be prepared using any suitable pharmaceutical carrier(s), for example aqueous gums, celluloses, silicates or oils and the dispersion or suspension then filled into a soft gelatin capsule.
- the daily oral dosage regimen will preferably be from about 0.01 mg/kg to about 50 mg/kg of total body weight.
- each oral dosage unit will contain the active ingredient in an amount of from about 0.5 mg to about 150 mg.
- an activate ingredient While it is possible for an activate ingredient to be administered alone, it is preferable to present it as a pharmaceutical formulation.
- Gastrin Releasing Peptide Receptor antagonist or a pharmaceutically acceptable salt or hydrate or solvate thereof given per day and duration of therapy can be ascertained by those skilled in the art using conventional course of treatment determination tests.
- the method of this invention of treating renal disease, preferably chronic renal disease, in mammals, including humans, comprises administering to a subject in need of such treatment an effective amount of a pharmaceutically active compound of the present invention.
- the invention also provides for the use of a Gastrin Releasing Peptide Receptor antagonist or a pharmaceutically acceptable salt or hydrate or solvate thereof in the manufacture of a medicament for use in treating renal disease, preferably chronic renal disease, in mammals, including humans.
- the invention also provides for a pharmaceutical composition for use in the treatment of renal disease, preferably chronic renal disease, which comprises a Gastrin Releasing Peptide Receptor antagonist or a pharmaceutically acceptable salt or hydrate or solvate thereof.
- the invention also provides for a process for preparing a pharmaceutical composition containing a Gastrin Releasing Peptide Receptor antagonist or a pharmaceutically acceptable salt or hydrate or solvate thereof which comprises bringing the Gastrin Releasing Peptide Receptor antagonist or a pharmaceutically acceptable salt or hydrate or solvate thereof into association with the pharmaceutically acceptable carrier or diluent.
- the compounds of the present invention can be co-administered with further active ingredients, such as compounds known to treat renal disease and particularly chronic renal disease.
- Example 1 Capsule Composition
- a oral dosage form for administering a Gastrin Releasing Peptide Receptor antagonist is produced by filing a standard two piece hard gelatin capsule with the ingredients in the proportions shown in Table I, below. Table I
- Example 2 Injectable Parenteral Composition
- An injectable form for administering a Gastrin Releasing Peptide Receptor antagonist is produced by stirring 1.5% by weight of a GRP Releasing Peptide antagonist in 10% by volume propylene glycol in water.
- Example 3 Tablet Composition
- sucrose, calcium sulfate dihydrate and a Gastrin Releasing Peptide Receptor antagonist shown in Table II below are mixed and granulated in the proportions shown with a 10% gelatin solution.
- the wet granules are screened, dried, mixed with the starch, talc and stearic acid, screened and compressed into a tablet.
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97939594A EP1007071A1 (en) | 1996-08-27 | 1997-08-27 | Methods of treating renal disease with a gastrin releasing peptide receptor antagonist |
JP10511880A JP2001500485A (en) | 1996-08-27 | 1997-08-27 | Method for treating renal disease using gastrin releasing peptide receptor antagonist |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2465396P | 1996-08-27 | 1996-08-27 | |
US60/024,653 | 1996-08-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998008532A1 true WO1998008532A1 (en) | 1998-03-05 |
Family
ID=21821712
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1997/015080 WO1998008532A1 (en) | 1996-08-27 | 1997-08-27 | Methods of treating renal disease with a gastrin releasing peptide receptor antagonist |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1007071A1 (en) |
JP (1) | JP2001500485A (en) |
WO (1) | WO1998008532A1 (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5215963A (en) * | 1989-10-24 | 1993-06-01 | Berlex Laboratories, Inc. | Solubilization and purification of the active gastrin releasing peptide receptor |
-
1997
- 1997-08-27 EP EP97939594A patent/EP1007071A1/en not_active Withdrawn
- 1997-08-27 WO PCT/US1997/015080 patent/WO1998008532A1/en not_active Application Discontinuation
- 1997-08-27 JP JP10511880A patent/JP2001500485A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5215963A (en) * | 1989-10-24 | 1993-06-01 | Berlex Laboratories, Inc. | Solubilization and purification of the active gastrin releasing peptide receptor |
Non-Patent Citations (2)
Title |
---|
LIFE SCIENCES, July 1995, Vol. 56, No. 7, MOODY et al., "BW2258U89: A GRP Receptor Antagonist Which Inhibits Small Cell Lung Cancer Growth", pages 521-529. * |
REGULATORY PEPTIDES, 21 October 1994, Vol. 53, DIETRICH et al., "Effects of BIM26226, A Potent and Specific Bombesin Receptor Antagonist, on Amylase Release and Binding of Bombesin-Like Peptides to AR4-2J Cells", pages 165-173. * |
Also Published As
Publication number | Publication date |
---|---|
EP1007071A1 (en) | 2000-06-14 |
JP2001500485A (en) | 2001-01-16 |
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