Patent EP0061138A2 successfully refreshed from Google Patents.
EP0061138A2
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Angiotropins of leukocytes and inflamed tissue: a new class of natural chemotropic protein mitogens for specific induction of directional growth of blood vessels, neovascularization of tissues and morphogenesis of blood vessel patterns, process for their biotechnical preparation and pharmaceutical compositions
Assignee: Max-Planck-Gesellschaft zur Förderung der Wissenschaften eV
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Filing: 1982-03-17
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Granted: —
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Expires: 2002-03-17
Abstract
Abstract The invention relates to new angiotropins of leukocytes and inflamed tissue which have the biological and physicochemical porperties stated in the patent claims. The compounds selectively stimulate the direction growth of blood vessels and lead to a neovascularization of tissue. The invention also relates to a biotechnical process for preparing and isolating the angiotropins and to pharmaceutical compositions containing them.
Inventors
- 👤 Josef H. Dr. Wissler
- 👤 Wolfgang Prof. Dr. Schaper
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-10 01:29
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/515; C07K16/00; C07K16/18; C07K16/22; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
163 words
A ngiotropins of leukocytes and inflamed tissue, characterized by the following properties: a) biological activities in vivo and in vifro: - specific chemotropic action on blood vessels in vivo; - induction of directional growth (chemotropism) of blood vessels along its concentration gradient; - during vessel sprouting, tips of growing vessel capillaries have increased capillary permeability (figure 1); - induction of neovascularization of tissues by directional in-growth of blood vessels (fig. 1 and 2); - they are substantially free of other biological effects b) physico-chemical properties: - electrophoretic migration in acrylamide matrices at a pH of 7.40 is anodic; - soluble in aqueous media including in 20 % ethanol at a pH value of at least 4.0 to 10; - constant temperature coefficient of solubility in ammonium sulfate solutions between -10°C and + 50°C; - they absorb reversibly in structure and biological activity on anion and cation exchangers, calcium phosphate gel and hydroxyapatite and can be subjected in native form to volume partition chromatography.
Claim 2
Dependent Claim
163 words
A ngiotropins of leukocytes and inflamed tissue, characterized by the following properties: a) biological activities in vivo and in vifro: - specific chemotropic action on blood vessels in vivo; - induction of directional growth (chemotropism) of blood vessels along its concentration gradient; - during vessel sprouting, tips of growing vessel capillaries have increased capillary permeability (figure 1); - induction of neovascularization of tissues by directional in-growth of blood vessels (fig. 1 and 2); - they are substantially free of other biological effects b) physico-chemical properties: - electrophoretic migration in acrylamide matrices at a pH of 7.40 is anodic; - soluble in aqueous media including in 20 % ethanol at a pH value of at least 4.0 to 10; - constant temperature coefficient of solubility in ammonium sulfate solutions between -10°C and + 50°C; - they absorb reversibly in structure and biological activity on anion and cation exchangers, calcium phosphate gel and hydroxyapatite and can be subjected in native form to volume partition chromatography.
Claim 3
Dependent Claim
117 words
Angiotropin (Monocyto-angiotropin) according to claim 1, characterized in that it is obtainable from mononuclear leukocytes and possesses the following additional properties: - effective threshold dose in vivo: < 2,5 fmol - molecular weight of the native protein (primary structure); approximately 4,500 dalton; - no protein quaternary structure in the form of physically bound peptide subunits: each of the native proteins consists of'only one peptide unit - soluble in an ammonium sulfate solution at 90% saturation (3.6 mol/1); - it contains, amongst others, the amino acids tyrosine, phenylalanine, alanine, glycine, valine, cysteine and aspartic acid; - absorption spectrum (UV, visible and near IR- range) as given in Fig. 3; - extinction coefficients according to the following Table I:
Claim 4
Dependent Claim
95 words
Angiotropin (granulocyto-angiotropin) according to claim 1, characterized in that it is obtainable from granulocytes and possesses the following additional properties: - effective threshold dose in vivo: < 50 fmol - molecular weight of the native protein (primary structure): approximately 35,000 dalton; - insoluble in an ammonium sulfate solution at 35 % saturation (1.4 mol/1); - it contains, amongst others the amino acids tyrosine, phenylalanine, alanine, glycine, valine, cysteine, aspartic acid, proline and arginine; - absorption spectrum (UV, visible and near IR- range) according to Fig. 4; - extinction coefficient according to the following Table II:
Claim 5
Dependent Claim
37 words
Process for production and isolation of the angiotropins according to claims 1 to 3, characterized by homogenizing leukocytes or inflamed tissue or culturing leukocytes and isolating the resultant angiotropins from the homogenates or the supernatant culture solution.
Claim 6
Dependent Claim
116 words
Process according to claim 4, characterized in that for obtaining monocyto-angiotropin a mixed leukocyte population or only monocytes are cultured, the mitosis of the cells is induced by.CON during culturing, after termination of culturing ammonium sulfate is added to the culture solution up to a 90% saturation, the precipitated proteins-are separated from the ammonium sulfate-containing supernatant, the supernatant is concentrated and purified by preparative moleculare sieve filtration, an anion exchange chromatography step, a cation exchange chromatography step, chromatography on hydroxyapatite, . zone precipitation chromatography and cascade molecular sieve filtration and in that the monocyto-angiotropin is isolated in highly purified form in the eluate of the cascade molecular sieve filtration after separation of the accompanying foreign proteins.
Claim 7
Dependent Claim
121 words
Process according to claim 4, characterized in that for obtaining granulocyto-angiotropin a mixed leukocyte population or only granulocytes are cultured, the mitosis of the cells is optionally induced by CON during culturing, after termination of culturing ammonium sulfate is added to the culture solution up to a 35 % saturation, the precipitated proteins are separated from the ammonium sulfate-containing supernatant, are redissolved and purified by an anion exchange chromatography step, a preparative molecular sieve filtration, a cation exchange chromatography step, a chromatography on hydroxyapatite, a zone precipitation chromatography and a cascade molecular sieve filtration and in that the granulocyto-angiotropin is isolated in highly purified form in the eluate of the cascade molecular sieve filtration after separation of the accompanying foreign proteins.
Claim 8
Dependent Claim
46 words
Pharmaceutical composition for specifically influencing the angiogenesis and the vascular condition of a tissue of the body of mammalians, characterized by a content of at least one angiotropin according to claims 1 to 3 or of at least one anti-angiotropin-immunoglobulin and usual carriers, adjuvants and additives.
Claim 9
Dependent Claim
36 words
Use of at least one angiotropin according to claims 1 to 3 or of at least one anti-angiotropin immunoglobulin for specifically influencing the angiogenesis and the vascular condition of a tissue of the body of mammalians.
References Cited (Backward Citations)
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