DE69627137T2 - Verwendung von pentosan polysulfat zur behandlung von narben in chronischer fortschreitender gefässerkrankungen - Google Patents
Verwendung von pentosan polysulfat zur behandlung von narben in chronischer fortschreitender gefässerkrankungenInfo
- Publication number
- DE69627137T2 DE69627137T2 DE69627137T DE69627137T DE69627137T2 DE 69627137 T2 DE69627137 T2 DE 69627137T2 DE 69627137 T DE69627137 T DE 69627137T DE 69627137 T DE69627137 T DE 69627137T DE 69627137 T2 DE69627137 T2 DE 69627137T2
- Authority
- DE
- Germany
- Prior art keywords
- pps
- pps according
- disease
- medicament
- pharmaceutically acceptable
- 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.)
- Expired - Fee Related
Links
- 229940043138 pentosan polysulfate Drugs 0.000 title claims description 89
- 208000019553 vascular disease Diseases 0.000 title claims description 11
- 230000000750 progressive effect Effects 0.000 title claims description 10
- 208000032544 Cicatrix Diseases 0.000 title claims description 7
- 231100000241 scar Toxicity 0.000 title claims description 7
- 230000037387 scars Effects 0.000 title claims description 7
- 238000011282 treatment Methods 0.000 title description 16
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 230000001684 chronic effect Effects 0.000 claims description 11
- 239000002552 dosage form Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 210000003734 kidney Anatomy 0.000 claims description 10
- 230000037390 scarring Effects 0.000 claims description 10
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 230000003902 lesion Effects 0.000 claims description 7
- 239000003826 tablet Substances 0.000 claims description 6
- 206010016654 Fibrosis Diseases 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 230000004761 fibrosis Effects 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 210000004204 blood vessel Anatomy 0.000 claims description 4
- 201000006370 kidney failure Diseases 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000006186 oral dosage form Substances 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 208000022461 Glomerular disease Diseases 0.000 claims description 3
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 208000020832 chronic kidney disease Diseases 0.000 claims description 3
- 238000000502 dialysis Methods 0.000 claims description 3
- 208000028208 end stage renal disease Diseases 0.000 claims description 3
- 201000000523 end stage renal failure Diseases 0.000 claims description 3
- 230000003176 fibrotic effect Effects 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 3
- 231100000852 glomerular disease Toxicity 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 230000036262 stenosis Effects 0.000 claims description 3
- 208000037804 stenosis Diseases 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000007894 caplet Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000007903 gelatin capsule Substances 0.000 claims description 2
- 239000007937 lozenge Substances 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000007939 sustained release tablet Substances 0.000 claims description 2
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 238000004090 dissolution Methods 0.000 claims 1
- 235000015424 sodium Nutrition 0.000 claims 1
- 102000008186 Collagen Human genes 0.000 description 26
- 108010035532 Collagen Proteins 0.000 description 26
- 229920001436 collagen Polymers 0.000 description 26
- 108020004999 messenger RNA Proteins 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 18
- 230000002860 competitive effect Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 239000002299 complementary DNA Substances 0.000 description 11
- 229920000669 heparin Polymers 0.000 description 11
- 229960002897 heparin Drugs 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- 102000007469 Actins Human genes 0.000 description 9
- 108010085238 Actins Proteins 0.000 description 9
- 238000002944 PCR assay Methods 0.000 description 8
- 239000003102 growth factor Substances 0.000 description 8
- 210000003584 mesangial cell Anatomy 0.000 description 8
- 238000003752 polymerase chain reaction Methods 0.000 description 8
- 241000699660 Mus musculus Species 0.000 description 7
- 239000003651 drinking water Substances 0.000 description 7
- 235000020188 drinking water Nutrition 0.000 description 7
- 238000010839 reverse transcription Methods 0.000 description 7
- 238000011830 transgenic mouse model Methods 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 208000034189 Sclerosis Diseases 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 102000029816 Collagenase Human genes 0.000 description 5
- 108060005980 Collagenase Proteins 0.000 description 5
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 4
- 102000007547 Laminin Human genes 0.000 description 4
- 108010085895 Laminin Proteins 0.000 description 4
- 102000005741 Metalloproteases Human genes 0.000 description 4
- 108010006035 Metalloproteases Proteins 0.000 description 4
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 4
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000013059 nephrectomy Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000001434 glomerular Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000008177 pharmaceutical agent Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 150000004804 polysaccharides Chemical class 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 102000004266 Collagen Type IV Human genes 0.000 description 2
- 108010042086 Collagen Type IV Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 239000012807 PCR reagent Substances 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000012197 amplification kit Methods 0.000 description 2
- 229920006318 anionic polymer Polymers 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 108010006025 bovine growth hormone Proteins 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000010820 immunofluorescence microscopy Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 208000037821 progressive disease Diseases 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 201000010174 renal carcinoma Diseases 0.000 description 2
- 239000003161 ribonuclease inhibitor Substances 0.000 description 2
- 230000002784 sclerotic effect Effects 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 229920001221 xylan Polymers 0.000 description 2
- -1 xylan sulfate Chemical class 0.000 description 2
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-OFKYTIFKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(tritiooxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO[3H])O[C@H]1N1C(=O)NC(=O)C(C)=C1 IQFYYKKMVGJFEH-OFKYTIFKSA-N 0.000 description 1
- WCOXQTXVACYMLM-UHFFFAOYSA-N 2,3-bis(12-hydroxyoctadecanoyloxy)propyl 12-hydroxyoctadecanoate Chemical compound CCCCCCC(O)CCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC(O)CCCCCC)COC(=O)CCCCCCCCCCC(O)CCCCCC WCOXQTXVACYMLM-UHFFFAOYSA-N 0.000 description 1
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 241001070947 Fagus Species 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229920001499 Heparinoid Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 208000005615 Interstitial Cystitis Diseases 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical class COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 101001075372 Mus musculus Gamma-glutamyl hydrolase Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102100037968 Ribonuclease inhibitor Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102000007000 Tenascin Human genes 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102100030859 Tissue factor Human genes 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- PYMYPHUHKUWMLA-VPENINKCSA-N aldehydo-D-xylose Chemical compound OC[C@@H](O)[C@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-VPENINKCSA-N 0.000 description 1
- 229930094280 aldehydo-D-xylose Natural products 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000964 angiostatic effect Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000001736 capillary Anatomy 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 210000005257 cortical tissue Anatomy 0.000 description 1
- MSJQCBORNZDNDU-UHFFFAOYSA-D decasodium 3-methoxy-6-[2-(6-methoxy-4,5-disulfonatooxyoxan-3-yl)oxy-5-[5-(5-methoxy-3,4-disulfonatooxyoxan-2-yl)oxy-3,4-disulfonatooxyoxan-2-yl]oxy-4-sulfonatooxyoxan-3-yl]oxy-4,5-disulfonatooxyoxane-2-carboxylate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].COC1COC(OC2COC(OC3COC(OC4COC(OC)C(OS([O-])(=O)=O)C4OS([O-])(=O)=O)C(OC4OC(C(OC)C(OS([O-])(=O)=O)C4OS([O-])(=O)=O)C([O-])=O)C3OS([O-])(=O)=O)C(OS([O-])(=O)=O)C2OS([O-])(=O)=O)C(OS([O-])(=O)=O)C1OS([O-])(=O)=O MSJQCBORNZDNDU-UHFFFAOYSA-D 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 229940043249 elmiron Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 210000003904 glomerular cell Anatomy 0.000 description 1
- 229960002849 glucosamine sulfate Drugs 0.000 description 1
- 150000004676 glycans Polymers 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 239000002554 heparinoid Substances 0.000 description 1
- 229940025770 heparinoids Drugs 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 108010024226 placental ribonuclease inhibitor Proteins 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003214 pyranose derivatives Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001180 sulfating effect Effects 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 230000008364 tissue synthesis Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000012762 unpaired Student’s t-test Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 150000004823 xylans Chemical class 0.000 description 1
- 238000007805 zymography Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/478,347 US5643892A (en) | 1995-06-07 | 1995-06-07 | Method of treating chronic progressive vascular diseases |
PCT/US1996/008367 WO1996040158A1 (en) | 1995-06-07 | 1996-06-03 | Method of treating chronic progressive vascular diseases |
Publications (2)
Publication Number | Publication Date |
---|---|
DE69627137D1 DE69627137D1 (de) | 2003-05-08 |
DE69627137T2 true DE69627137T2 (de) | 2003-12-04 |
Family
ID=23899571
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE69627137T Expired - Fee Related DE69627137T2 (de) | 1995-06-07 | 1996-06-03 | Verwendung von pentosan polysulfat zur behandlung von narben in chronischer fortschreitender gefässerkrankungen |
Country Status (7)
Country | Link |
---|---|
AR (1) | AR003957A1 (da) |
AT (1) | ATE235908T1 (da) |
DE (1) | DE69627137T2 (da) |
DK (1) | DK0809505T3 (da) |
HK (1) | HK1005497A1 (da) |
PT (1) | PT809505E (da) |
RU (1) | RU2196589C2 (da) |
-
1996
- 1996-06-03 DK DK96917917T patent/DK0809505T3/da active
- 1996-06-03 RU RU97116166A patent/RU2196589C2/ru not_active IP Right Cessation
- 1996-06-03 AT AT96917917T patent/ATE235908T1/de not_active IP Right Cessation
- 1996-06-03 DE DE69627137T patent/DE69627137T2/de not_active Expired - Fee Related
- 1996-06-03 PT PT96917917T patent/PT809505E/pt unknown
- 1996-06-06 AR ARP960102973A patent/AR003957A1/es not_active Application Discontinuation
-
1998
- 1998-06-01 HK HK98104683A patent/HK1005497A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
DK0809505T3 (da) | 2003-07-07 |
DE69627137D1 (de) | 2003-05-08 |
PT809505E (pt) | 2003-08-29 |
AR003957A1 (es) | 1998-09-30 |
RU2196589C2 (ru) | 2003-01-20 |
HK1005497A1 (en) | 1999-01-15 |
ATE235908T1 (de) | 2003-04-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Gambaro et al. | Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats | |
DE3856321T2 (de) | Sulfatierte Polysaccharide mit antiinflammatorischer Aktivität | |
DE69431433T2 (de) | Zusammensetzungen und verfahren zur reparatur und vorbeugung fibrotischer verletzungen | |
DE69928410T2 (de) | Selenium enthaltende zusammensetzung zur behandlung von systemischen entzündungssyndromen | |
DE69731386T2 (de) | Verfahren zur behandlung von asthma mit o-desulfatisiertem heparin | |
DE69212620T2 (de) | Verwendung von Glycosaminoglycanen zur Behandlung von diabetischer Nephropathie und diabetischer Neuropathie | |
DE69731610T2 (de) | Orale verabreichung wirksamer mengen von hyaluronsäure | |
DE69833333T2 (de) | Pharmazeutische zusammensetzung enthaltend geweihextrakte von cervus nippon mit wachstumsstimulierender aktivität auf hematopoietische stammzellen und megakaryozyten | |
WO1998001143A1 (de) | Verwendung von artischocken-(cynara)-extrakten | |
DE69012620T2 (de) | Unterdrückung der Synthese und der Sekretion des Nebenschilddrüsenhormons mit Vitamin D3-Derivaten. | |
DE2635065C2 (de) | Verfahren zur halbkontinuierlichen Behandlung von Gesamtblut zur Herstellung von biologisch aktiven hämatopoetischen Chalonextrakten | |
DE69617415T2 (de) | Kanzeröse metastasenbildung unterdrückendes antikrebsmittel | |
DE69521388T2 (de) | Verwendung von Glycosaminoglycanen zur Herstellung eines Arzneimittels zur Behandlung des chronischen Nierenversagens | |
DE69917796T2 (de) | Decursin-enthaltende pharmazeutische zusammensetzungen | |
EP0809505B1 (en) | Use of pentosan polysulfate for the resolution of scars in chronic progressive vascular diseases | |
DE112009005041T5 (de) | Verfahren der Extraktzubereitung aus Longankern und die Anwendung des Longankernextrakts | |
AU750182B2 (en) | Method of treating chronic progressive vascular scarring diseases | |
DE69627137T2 (de) | Verwendung von pentosan polysulfat zur behandlung von narben in chronischer fortschreitender gefässerkrankungen | |
CH639560A5 (en) | Pharmaceutical preparation having a prolonged uniform active compound release | |
EP1047434A2 (de) | Verwendung von glykosaminoglykanen zur herstellung von pharmazeutischen zubereitungen zur behandlung von mit diabetes assoziierten augenkrankheiten | |
DE2201669C3 (de) | Pyrogenfreier Blutplasmaersatz | |
DE69421174T2 (de) | Verwendung von adenosin zur herstellung eines arzneimittels zur behandlung entzüdlicher reaktionen der lunge | |
EP1244442B1 (de) | Verfahren zur auffindung von nukleotidsyntheseinhibitoren mit weniger nebenwirkungen | |
DE2162343A1 (de) | Antipeptisch wirksames arzneimittel | |
EP1044007B1 (de) | Mannose zur bekämpfung der proteinverlust-enteropathie |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
8364 | No opposition during term of opposition | ||
8339 | Ceased/non-payment of the annual fee |