EP0318488A1 - Stimulation de l'angiogenese et promotion de l'endothelialisation - Google Patents

Stimulation de l'angiogenese et promotion de l'endothelialisation

Info

Publication number
EP0318488A1
EP0318488A1 EP87905152A EP87905152A EP0318488A1 EP 0318488 A1 EP0318488 A1 EP 0318488A1 EP 87905152 A EP87905152 A EP 87905152A EP 87905152 A EP87905152 A EP 87905152A EP 0318488 A1 EP0318488 A1 EP 0318488A1
Authority
EP
European Patent Office
Prior art keywords
inflammatory compound
angiogenesis
inflammatory
proline
composition
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.)
Withdrawn
Application number
EP87905152A
Other languages
German (de)
English (en)
Other versions
EP0318488A4 (fr
Inventor
Brian Richard Mcauslan
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.)
Biota Scientific Management Pty Ltd
Original Assignee
Biota Scientific Management Pty Ltd
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 Biota Scientific Management Pty Ltd filed Critical Biota Scientific Management Pty Ltd
Publication of EP0318488A1 publication Critical patent/EP0318488A1/fr
Publication of EP0318488A4 publication Critical patent/EP0318488A4/fr
Withdrawn legal-status Critical Current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
    • A61K31/60—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.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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.
EP19870905152 1986-08-18 1987-08-10 Stimulation de l'angiogenese et promotion de l'endothelialisation. Withdrawn EP0318488A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU7521/86 1986-08-18
AUPH752186 1986-08-18

Publications (2)

Publication Number Publication Date
EP0318488A1 true EP0318488A1 (fr) 1989-06-07
EP0318488A4 EP0318488A4 (fr) 1990-02-26

Family

ID=3771766

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19870905152 Withdrawn EP0318488A4 (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)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03109324A (ja) * 1989-09-22 1991-05-09 Microbial Chem Res Found 血管新生阻害剤
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
JP2004262776A (ja) * 2003-02-21 2004-09-24 Teikoku Seiyaku Co Ltd 血管新生促進剤
MXPA06011851A (es) 2004-04-14 2006-12-14 Genentech Inc Composiciones y metodos para moduilar el desarrollo vascular.

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2515189A (en) * 1948-10-12 1950-07-18 Samson Preservation of leucocytes in blood
BE626119A (fr) * 1961-12-19
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
GB1518333A (en) * 1975-05-30 1978-07-19 Science Union & Cie Pharmaceutical compositions containing a ypsilon-resorcylic acid derivative
JPS5829706A (ja) * 1981-08-14 1983-02-22 Toko Yakuhin Kogyo Kk 消炎鎮痛外用剤
CA1229554A (fr) * 1983-04-18 1987-11-24 Warner-Lambert Company Compose pharmaceutique topique d'acide meclofenamique
MX163953B (es) * 1984-03-27 1992-07-03 Univ New Jersey Med Procedimiento para preparar una matriz biodegradable a base de colageno
EP0294380A4 (fr) * 1986-02-18 1990-02-20 Biota Scient Management Stimulation de l'angiogenese.

Also Published As

Publication number Publication date
ZA876079B (en) 1988-06-29
EP0318488A4 (fr) 1990-02-26
WO1988001166A1 (fr) 1988-02-25
JPH01503705A (ja) 1989-12-14

Similar Documents

Publication Publication Date Title
Taylor et al. Protamine is an inhibitor of angiogenesis
US5552162A (en) Method for improvement of scar size and appearance
TWI257307B (en) Pharmaceutical composition for cardiac tissue repair
Barker et al. The time course of loss of dopaminergic neurons and the gliotic reaction surrounding grafts of embryonic mesencephalon to the striatum
Niall et al. The effect of epidermal growth factor on wound healing in mice
US6287606B1 (en) Methods of enhancing wound healing and tissue repair
US5155038A (en) Use of thrombospondin to promote wound healing
KR20050086949A (ko) 콜라졸리를 사용한 조성물 및 방법
US5036046A (en) Method for enhancing healing of corneal endothelial wounds
US5902609A (en) Composition for the control of wound scar production
Tripathi et al. Prospects for epidermal growth factor in the management of corneal disorders
CA2551525A1 (fr) Composition pharmaceutique pour derives peptidiques de la thrombine
US5051443A (en) Method for enhancing healing of corneal endothelial wounds
CA2246418A1 (fr) Inhibiteur de la neoformation de vaisseaux sanguins
CA2058597C (fr) Compositions cicatrisantes a base de facteur de croissance de fibroblaste et d'acide ascorbique
JP3149180B2 (ja) 瘢痕治療のためのカルシウム拮抗薬の使用
Sun et al. Localized propranolol delivery from a copper-loaded hydrogel for enhancing infected burn wound healing via adrenergic β-receptor blockade
EP0318488A1 (fr) Stimulation de l'angiogenese et promotion de l'endothelialisation
US6174541B1 (en) Skin aging and wound treatment using cell migration agents
Di-Silvio A novel application of two biomaterials for the delivery of growth hormone and its effect on osteoblasts
WO1989001489A1 (fr) Regulation de l'angiogenese et compositions et procedes prevus a cet effet
EP0294380A1 (fr) Stimulation de l'angiogenese
Fossum et al. TP508 (Chrysalin®) Reverses Endothelial Dysfunction and Increases Perfusion and Myocardial Function in Hearts With Chronic Ischemia
US5616576A (en) Controlling bone resorption with pyrroloquinoline quinone (PQQ) and related compounds
EA014296B1 (ru) Средство, активирующее стволовые клетки и/или клетки-предшественники

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19890216

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LI LU NL SE

A4 Supplementary search report drawn up and despatched

Effective date: 19900226

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19910301