WO1988001166A1 - Stimulation de l'angiogenese et promotion de l'endothelialisation - Google Patents
Stimulation de l'angiogenese et promotion de l'endothelialisation Download PDFInfo
- Publication number
- WO1988001166A1 WO1988001166A1 PCT/AU1987/000256 AU8700256W WO8801166A1 WO 1988001166 A1 WO1988001166 A1 WO 1988001166A1 AU 8700256 W AU8700256 W AU 8700256W WO 8801166 A1 WO8801166 A1 WO 8801166A1
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- WO
- WIPO (PCT)
- Prior art keywords
- inflammatory compound
- angiogenesis
- inflammatory
- proline
- composition
- Prior art date
Links
- 230000026341 positive regulation of angiogenesis Effects 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 26
- 230000033115 angiogenesis Effects 0.000 claims abstract description 25
- 230000002491 angiogenic effect Effects 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 17
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 230000004936 stimulating effect Effects 0.000 claims abstract description 9
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims abstract description 8
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims abstract description 7
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 claims abstract description 4
- BYHXLDZDSZVDJH-UHFFFAOYSA-N acetic acid;1,3-thiazole Chemical compound CC(O)=O.C1=CSC=N1 BYHXLDZDSZVDJH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 210000002889 endothelial cell Anatomy 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 13
- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 claims description 8
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical group OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
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- 238000009792 diffusion process Methods 0.000 claims description 5
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- IADUEWIQBXOCDZ-UHFFFAOYSA-N (2S)-azetidine-2-carboxylic acid Natural products OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 claims description 4
- OMGHIGVFLOPEHJ-BYPYZUCNSA-N (2s)-2,5-dihydro-1h-pyrrole-2-carboxylic acid Chemical compound OC(=O)[C@H]1NCC=C1 OMGHIGVFLOPEHJ-BYPYZUCNSA-N 0.000 claims description 4
- 101800003838 Epidermal growth factor Proteins 0.000 claims description 4
- 125000000174 L-prolyl group Chemical class [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims description 4
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 3
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- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims 3
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- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
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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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- 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
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/425—Thiazoles
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Definitions
- This invention relates to the control of angiogenesis, and methods and compositions therefor.
- a method for stimulating angiogenesis in a mammal characterized by the use of an anti-inflammatory agent.
- 3T3-cell derived growth factor McAuslan et al. , 1980
- tumor-derived growth factor Klagsbrun et al.. , 1982
- ECGF endothelial cell growth stimulator
- concentrations of copper ions can induce neovascularisation in the anterior eye chamber or corneal pocket and also migration of endothelial cells in culture (McAuslan, 1979; McAuslan and Gole, 1980; McAuslan and Reilly, 1980).
- an ideal agent for control of angiogenesis should have a direct action, and should itself be anti-inflammatory.
- a further limitation is imposed by the necessity for the agent to penetrate the target organ.
- NB also called hydratropic acids 2— henylpropanoic acids
- a method of stimulating angiogenesis in a mammal comprising the step of administering to that animal an anti-in lammatory compound.
- a method of stimulating endothelialisation in a mammal comprising the step of administering to that mammal an anti-inflammatory compound.
- the anti-inflammatory compound is preferably selected from the group which includes salicylic acid, anthranilic acid, phenyl acetic acid, and thiazole acetic acid, and their angiogenically-active analogues and derivatives.
- the anti-inflammatory compound has a directly-acting angiogenic effect.
- the compound comprises an aromatic carboxylic acid group.
- the compound is administered so as to achieve a diffusion gradient of concentration to which endothelial cells respond.
- Combinations of two or more compounds according to the invention may optionally be used.
- Combinations of one or more compounds according to the invention together with one or more other stimulators of angiogenesis may also optionally be used.
- Said second stimulator is suitably a modulator of collagen synthesis or of collagen fibril assembly.
- the modulator is an inhibitor of the ' activity of the enzyme proline hydroxylase.
- the inhibitory agent is selected from the group which includes cis-4-hyroxy-L-proline, 3, 4-dehydro-L-proline, L-azetidine-2-carboxylic acid, L-proline analogues, and their angiogenically-active analogues and derivatives.
- said second stimulator of angiogenesis is epidermal growth factor or a pharmacologically active analogue, fragment or derivative thereof.
- the compound according to the invention may optionally be administered in a slow-release form or in a biodegradable matrix.
- the corneal pocket assay in rabbits as described by Gimbrone et al. (1974) was used according to the modification of McAuslan and Gole (1981).
- McAuslan et al_. , 9183 it is extremely difficult to distinguish a directly acting angiogenic stimulus from one which is mediated by leukocytes (McAuslan et al_. , 9183).
- endothelial cell migration is a primary event in neovascularisation, and since there is a correlation between the ability of certain metal ions to induce vascularisation and their ability to cause migration of cultured cells, such migration has been suggested (McAuslan 1979) as the basis for a quantitative assay of angiogenic activity. There is comparatively little information on the correlation between this activity and neovascularising activity, and furthermore, a number of unrelated substances will induce migration of cultured endothelial cells and neovascularisation (McAuslan- 1979) Proliferation of endothelial cells is thought to be a response secondary to cell migration during new vessel formation. There are reports of low-molecular-weight neovasculogenic activities that can stimulate proliferation of cultured endothelial cells. However, the proliferative responses have been marginal and the reports are not in accord as to the minimal conditions or cell type necessary.
- Each polymer fragment is impregnated with approximately 0.5 mg of the solid agent to be tested, so that the agent diffuses out of the polymer and sets up a concentration gradient which changes with time.
- the corneal pocket assay of Gimbrone et. a _ (1974) as modified by Gole and McAuslan (1981) was used on New Zealand white rabbits of 2-3kg body weight. Opposite eyes of each animal were used as control and test, respectively. The results were documented photographically and histologically 10 days postoperation.
- Anti-inflammatory agents were tested for angiogenic activity in the subcutaneous implant assay in rabbits as described above. The results are shown in Table 2. Both flufenamic acid and diclofenac showed strong activity in stimulating vascularization. Only one of twelve controls showed any activity, giving a weak response.
- Elvax pellets contained 0.05* mg test'-agent per mm , i.e. equivalent to 2 x 10 -4M.
- Diclofenac 10 "5 M 145 31.31 10 " ⁇ M 111 33.60 10 ⁇ 7 M 76 28.i ⁇
- the present invention is capable of application in a wide variety of clinical fields.
- Stimulation of angiogenesis can be used to enhance the healing of burns and wounds, especially those involving large tissue defects, acceptance of skin or organ grafts, and can also be used in reconstructive and cosmetic surgery, including the use of subdermal implants, and in prosthetic surgery, particularly that involving vascular prostheses.
- Such stimulation may be used in any situation wherein endothelial cell migration and regeneration of endothelium are advantageous, or where an increase in blood flow is desirable, e.g., stroke, heart disease, or foetal blood insufficiency.
- the method according to the invention could be used in the following situations: a) Where development of a capillary network would be advantageous, e.g. Surgical repair, wound healing, b) Where stimulation of endothelialisation would be advantageous, . e.g. Synthetic or natural graft materials. c) Where healing may be enhanced by either angiogenic or anti-inflammatory action, e.g. ImpIantable prosthetic devices.
- This application excludes the use of Diclofenac as an anti-inflammatory agent which might improve the performance of cardiac pacemaker electrodes.
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Abstract
Un procédé, permettant de stimuler l'angiogénèse ou l'endothélialisation chez un mammifère, consiste à administrer audit mammifère un composé anti-inflammatoire. Celui-ci a de préférence un effet angiogène agissant directement; les composés préférés comportent de l'acide salicyclique, de l'acide anthranilique, de l'acide acétique de phényle et de l'acide acétique de thiazole. Un composé anti-inflammatoire peut être administré en même temps qu'un second stimulateur de l'angiogénèse. Des compositions et des articles sont également revendiqués.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPH752186 | 1986-08-18 | ||
AUPH7521 | 1986-08-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1988001166A1 true WO1988001166A1 (fr) | 1988-02-25 |
Family
ID=3771766
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/AU1987/000256 WO1988001166A1 (fr) | 1986-08-18 | 1987-08-10 | Stimulation de l'angiogenese et promotion de l'endothelialisation |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0318488A4 (fr) |
JP (1) | JPH01503705A (fr) |
WO (1) | WO1988001166A1 (fr) |
ZA (1) | ZA876079B (fr) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0424193A2 (fr) * | 1989-09-22 | 1991-04-24 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | L'utilisation de l'actinonin pour la fabrication d'un médicament pour l'inhibition de l'angiogenèse |
WO1998042329A1 (fr) * | 1997-03-21 | 1998-10-01 | Mitsubishi Chemical Corporation | Preventifs et/ou remedes destines a des affections provoquees par une neovascularisation anormale |
US6660283B2 (en) * | 1997-12-19 | 2003-12-09 | Societe L'oreal S.A. | Use of cinnamic acid, or of at least one of its derivatives in a cosmetic composition |
WO2004073717A1 (fr) * | 2003-02-21 | 2004-09-02 | Teikoku Seiyaku Co., Ltd. | Promoteur de la croissance de vaisseaux sanguins |
US8790646B2 (en) | 2004-04-14 | 2014-07-29 | Genentech Inc. | Compositions and methods for modulating vascular development |
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US2515189A (en) * | 1948-10-12 | 1950-07-18 | Samson | Preservation of leucocytes in blood |
GB1032253A (en) * | 1961-12-19 | 1966-06-08 | Fo We Forschungs Und Verwertun | Coumarin derivatives and process for the production thereof |
US3873715A (en) * | 1973-04-06 | 1975-03-25 | Univ Miami | Therapeutic agent for improving cardiovascular function |
US3928587A (en) * | 1974-08-16 | 1975-12-23 | Philip Nicholas Sawyer | Method of conditioning vascular systems by administering 3,5 dichloroaspirin and method of evaluating pharmaceutical compounds |
US4132787A (en) * | 1975-05-30 | 1979-01-02 | Science Union Et Cie | Pharmaceutical compositions containing a gamma-resorcylic acid derivative in the treatment of thrombosis |
US4545992A (en) * | 1981-08-14 | 1985-10-08 | Toko Yakuhin Industry Co., Ltd. | Pharmaceutical preparations |
AU560035B2 (en) * | 1983-04-18 | 1987-03-26 | Warner-Lambert Company | Meclofenamic acid topical pharmaceutical composition |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL74715A0 (en) * | 1984-03-27 | 1985-06-30 | Univ New Jersey Med | Biodegradable matrix and methods for producing same |
WO1987004925A1 (fr) * | 1986-02-18 | 1987-08-27 | Biota Scientific Management Pty. Ltd. | Stimulation de l'angiogenese |
-
1987
- 1987-08-10 EP EP19870905152 patent/EP0318488A4/fr not_active Withdrawn
- 1987-08-10 WO PCT/AU1987/000256 patent/WO1988001166A1/fr not_active Application Discontinuation
- 1987-08-10 JP JP62504759A patent/JPH01503705A/ja active Pending
- 1987-08-17 ZA ZA876079A patent/ZA876079B/xx unknown
Patent Citations (7)
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US2515189A (en) * | 1948-10-12 | 1950-07-18 | Samson | Preservation of leucocytes in blood |
GB1032253A (en) * | 1961-12-19 | 1966-06-08 | Fo We Forschungs Und Verwertun | Coumarin derivatives and process for the production thereof |
US3873715A (en) * | 1973-04-06 | 1975-03-25 | Univ Miami | Therapeutic agent for improving cardiovascular function |
US3928587A (en) * | 1974-08-16 | 1975-12-23 | Philip Nicholas Sawyer | Method of conditioning vascular systems by administering 3,5 dichloroaspirin and method of evaluating pharmaceutical compounds |
US4132787A (en) * | 1975-05-30 | 1979-01-02 | Science Union Et Cie | Pharmaceutical compositions containing a gamma-resorcylic acid derivative in the treatment of thrombosis |
US4545992A (en) * | 1981-08-14 | 1985-10-08 | Toko Yakuhin Industry Co., Ltd. | Pharmaceutical preparations |
AU560035B2 (en) * | 1983-04-18 | 1987-03-26 | Warner-Lambert Company | Meclofenamic acid topical pharmaceutical composition |
Non-Patent Citations (8)
Title |
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DERWENT ABSTRACT Accession No. 1983-727103, Class B04, SU,A1, 959784 (Mosc Medial Stomat) 23 September 1982 (23.09.82) * |
Derwent Soviet Inventions Illustrated, Vol. V, No. 49, issued 14 July 1975, Pharmaceuticals p. 7, SU 406393 (Tevlina) 10 July 1974 (10.07.74) * |
McAUSLAN, B.R. and G.A. GOLE (1980) Trans. Ophthalmol. Soc. U.K. 100 (3) 354-358 * |
PATENT ABSTRACTS OF JAPAN, C-105 page 35, JP,A, 57-024308 (NITTO DENKI KOGYO K.K.) 8 February 1982 (08.02.82) * |
PATENT ABSTRACTS OF JAPAN, C-249 page 9, JP,A, 59-116218 (KOUWA K.K.) 5 July 1984 (05.07.84) * |
PATENT ABSTRACTS OF JAPAN, C-316, page 68, JP,A, 60-139621 (GRELAN SEIYAKU K.K.) 24 July 1985 (24.07.85) * |
PATENT ABSTRACTS OF JAPAN, C-360, page 86, JP,A, 61-044811 (SS Pharmaceut Co. Ltd) 4 March 1986 (04.03.86) * |
See also references of EP0318488A4 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0424193A2 (fr) * | 1989-09-22 | 1991-04-24 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | L'utilisation de l'actinonin pour la fabrication d'un médicament pour l'inhibition de l'angiogenèse |
EP0424193A3 (en) * | 1989-09-22 | 1991-07-17 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | Use of actinonin for angiogenesis inhibition |
US5134156A (en) * | 1989-09-22 | 1992-07-28 | Zaidan Hojin Biseibutsu Kagaku Kai | Pharmaceutical composition and method for angiogenesis inhibition |
WO1998042329A1 (fr) * | 1997-03-21 | 1998-10-01 | Mitsubishi Chemical Corporation | Preventifs et/ou remedes destines a des affections provoquees par une neovascularisation anormale |
US6660283B2 (en) * | 1997-12-19 | 2003-12-09 | Societe L'oreal S.A. | Use of cinnamic acid, or of at least one of its derivatives in a cosmetic composition |
WO2004073717A1 (fr) * | 2003-02-21 | 2004-09-02 | Teikoku Seiyaku Co., Ltd. | Promoteur de la croissance de vaisseaux sanguins |
US8790646B2 (en) | 2004-04-14 | 2014-07-29 | Genentech Inc. | Compositions and methods for modulating vascular development |
Also Published As
Publication number | Publication date |
---|---|
ZA876079B (en) | 1988-06-29 |
EP0318488A4 (fr) | 1990-02-26 |
EP0318488A1 (fr) | 1989-06-07 |
JPH01503705A (ja) | 1989-12-14 |
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