MXPA99010582A - Use of low-molecular-weight heparins for preventing and treating central nervous system trauma - Google Patents
Use of low-molecular-weight heparins for preventing and treating central nervous system traumaInfo
- Publication number
- MXPA99010582A MXPA99010582A MXPA/A/1999/010582A MX9910582A MXPA99010582A MX PA99010582 A MXPA99010582 A MX PA99010582A MX 9910582 A MX9910582 A MX 9910582A MX PA99010582 A MXPA99010582 A MX PA99010582A
- Authority
- MX
- Mexico
- Prior art keywords
- molecular weight
- low molecular
- weight heparin
- dci
- trauma
- Prior art date
Links
- 229920000669 heparin Polymers 0.000 title claims abstract description 31
- 210000003169 Central Nervous System Anatomy 0.000 title claims abstract description 10
- 208000001738 Nervous System Trauma Diseases 0.000 title claims abstract description 8
- 206010022114 Injury Diseases 0.000 claims abstract description 22
- HTTJABKRGRZYRN-UHFFFAOYSA-N Enoxaparin 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 claims description 34
- 239000003055 low molecular weight heparin Substances 0.000 claims description 20
- 229960002897 Heparin Drugs 0.000 claims description 11
- ZFGMDIBRIDKWMY-PASTXAENSA-N Heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 claims description 11
- 230000002265 prevention Effects 0.000 claims description 9
- OHJKXVLJWUPWQG-IUYNYSEKSA-J (4S,6R)-6-[(2R,4R)-4,6-dihydroxy-5-(sulfonatoamino)-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,4-dihydroxy-5-sulfonatooxyoxane-2-carboxylate Chemical compound O[C@@H]1C(NS([O-])(=O)=O)C(O)O[C@H](COS([O-])(=O)=O)C1O[C@H]1C(OS([O-])(=O)=O)[C@@H](O)C(O)C(C([O-])=O)O1 OHJKXVLJWUPWQG-IUYNYSEKSA-J 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 229960000610 Enoxaparin Drugs 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 229960004969 Dalteparin Drugs 0.000 claims description 2
- 229960000899 Nadroparin Drugs 0.000 claims description 2
- 229940090880 ardeparin Drugs 0.000 claims description 2
- 229940107792 certoparin Drugs 0.000 claims description 2
- 229960003828 danaparoid Drugs 0.000 claims description 2
- 229940079593 drugs Drugs 0.000 claims description 2
- 229960004762 parnaparin Drugs 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- VKMGSWIFEHZQRS-NSHDSACASA-N (1R)-1-(3,4-dichlorophenyl)-2-(propan-2-ylamino)ethanol Chemical compound CC(C)NC[C@H](O)C1=CC=C(Cl)C(Cl)=C1 VKMGSWIFEHZQRS-NSHDSACASA-N 0.000 claims 9
- 150000001875 compounds Chemical class 0.000 claims 2
- XEKSTYNIJLDDAZ-JASSWCPGSA-D decasodium;(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5R,6R)-6-[(2R,3S,4S,5R,6R)-2-carboxylato-4-hydroxy-6-[(2R,3S,4R,5R,6S)-4-hydroxy-6-methoxy-5-(sulfonatoamino)-2-(sulfonatooxymethyl)oxan-3-yl]oxy-5-sulfonatooxyoxan-3-yl]oxy-5-(sulfonatoamino)-4-sulfonatooxy-2-(sul Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].O[C@@H]1[C@@H](NS([O-])(=O)=O)[C@@H](OC)O[C@H](COS([O-])(=O)=O)[C@H]1O[C@H]1[C@H](OS([O-])(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS([O-])(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS([O-])(=O)=O)O4)NS([O-])(=O)=O)[C@H](O3)C([O-])=O)O)[C@@H](COS([O-])(=O)=O)O2)NS([O-])(=O)=O)[C@H](C([O-])=O)O1 XEKSTYNIJLDDAZ-JASSWCPGSA-D 0.000 claims 1
- 229920001542 oligosaccharide Polymers 0.000 claims 1
- 150000002482 oligosaccharides Polymers 0.000 claims 1
- 229960005496 reviparin Drugs 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 208000005765 Traumatic Brain Injury Diseases 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000005194 fractionation Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 206010018987 Haemorrhage Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 230000000740 bleeding Effects 0.000 description 2
- 231100000319 bleeding Toxicity 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- KHIWWQKSHDUIBK-UHFFFAOYSA-M AC1L4ZKD Chemical compound [O-]I(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-M 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 206010001954 Amnestic disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101700044814 CYO2 Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N Carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N D-sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010015037 Epilepsy Diseases 0.000 description 1
- 229940012356 Eye Drops Drugs 0.000 description 1
- WZUVPPKBWHMQCE-VYIIXAMBSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@@]2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-VYIIXAMBSA-N 0.000 description 1
- 229960003132 Halothane Drugs 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N Halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 description 1
- 229940051866 Mouthwash Drugs 0.000 description 1
- 210000004400 Mucous Membrane Anatomy 0.000 description 1
- 229940100662 Nasal Drops Drugs 0.000 description 1
- 208000009025 Nervous System Disease Diseases 0.000 description 1
- 206010029305 Neurological disorder Diseases 0.000 description 1
- 241000283898 Ovis Species 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 239000004698 Polyethylene (PE) Substances 0.000 description 1
- 206010039203 Road traffic accident Diseases 0.000 description 1
- 208000008513 Spinal Cord Injury Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Vitamin C Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000240 adjuvant Effects 0.000 description 1
- 230000001058 adult Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000007068 beta-elimination reaction Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000003479 dental cement Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229950008597 drug INN Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 150000004676 glycans Polymers 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000000968 intestinal Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
- 230000001936 parietal Effects 0.000 description 1
- 238000009527 percussion Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- YOQDYZUWIQVZSF-UHFFFAOYSA-N sodium borohydride Substances [BH4-].[Na+] YOQDYZUWIQVZSF-UHFFFAOYSA-N 0.000 description 1
- ODGROJYWQXFQOZ-UHFFFAOYSA-N sodium;boron(1-) Chemical compound [B-].[Na+] ODGROJYWQXFQOZ-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960005062 tinzaparin Drugs 0.000 description 1
- 230000000699 topical Effects 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Abstract
The invention concerns the use of low-molecular-weight heparins for preventing and treating central nervous system trauma, in particular spinal, cranial or craniospinal trauma.
Description
USE DZ LOW MOLECULAR WEIGHT HEPARINS FOR THE PREVENTION AND TREATMENT OF TRAUMA TO THE NERVOUS SYSTEM
CENTRAL Background of the invention:
The present invention concerns the use of low molecular weight heparins for the prevention and treatment of central nervous system trauma, and especially spinal, cranial or cranio-spinal trauma. The invention also concerns the use of low molecular weight heparins for the preparation of a drug useful for the prevention and treatment of central nervous system trauma, and especially spinal, cranial or cranio-spinal trauma. Standard heparin is a sulfated polysaccharide, with an average molecular weight of 12,000 to 15,000 daltons, isolated from the intestinal mucous membranes of the cow, sheep or pig. Heparin is used clinically for the prevention and treatment of thromboembolic disorders, but sometimes causes bleeding. For about ten years, heparin has been progressively replaced by low molecular weight heparins, which do not present, or present to a lesser degree, the inconvenience of causing bleeding and do not need more than one injection per day, instead of 2. to 3 injections per day for standard heparin. These low molecular weight heparins are prepared REF .: 31874 especially by means of fractionation, controlled depolymerization of heparin or by means of chemical synthesis. They show an activity ratio of Xa / anti-activity activity greater than 2. It has now been found that low-molecular-weight heparins reduce the size of central nervous system trauma and especially spinal-cranial or cranio-spinal trauma - Central nervous system trauma (CNS trauma or neurotrau) include brain trauma , (brain trauma) and spinal cord trauma (spinal trauma). They are the result of a crash frequently at the level of the central nervous system (automobile accident, motorcycle, ski, swimming pool ...) but they are never accompanied by a fracture. The consequences of these traumas are neurological disorders such as epilepsy, altered consciousness, motor problems, amnesia, aggression and psycho-affective deficit. According to the invention, a low molecular weight heparin having an average molecular weight of between 1000 and 10000 daltons, especially between 1500 and 6000 daltons and, in particular, between 4000 and 5000 daltons, is preferably used. They can be prepared (low molecular weight heparins) by different procedures from heparin: - fractionation by means of solvents (FR2440376, US4692435); fractionation on anionic resin (FR2453875) - gel filtration (BARROWCLIFFE, Throm. Res. 12, 27-36 (1977)); - Affinity chromatography (US4401758); - Depolymerization controlled by means of a chemical agent: nitrous acid (EP14184, EP37319, EP76279,
EP623629, FR2503714, US4804652, 0813276), ß elimination from an ester of heparin (EP40144, US5389618), periodate (EP287477), sodium borohydride (EP347588, EP380943), ascorbic acid (US 4533549); hydrogen peroxide (US4629699, US4791195), quaternary ammonium hydroxide from a quaternary ammonium salt of heparin (US4981955), alkali metal hydroxide (EP380943, EP347588) or enzymatically (EP64452, US4396762, EP244235, EP244236; US 4826827; US 3766166); by means of irradiation (EP 269981). Some can also be prepared by chemical synthesis (US4801583, US4818816, EP165134, EP84999, FR2535306). Among the low molecular weight heparins, there may be mentioned, more particularly, enoxaparin (INN), marketed by RHONE-POULENC RORER; nadroparin (DCI), marketed by SANOFI; Parnaparin (DCI), marketed by OPOCRIN-ALFA; the reviparina (DCI), marketed by KNOLL; Dalteparin (DCI), marketed by KABI PHARMACIA; Tinzaparin (DCI), marketed by NOVO-NORDISK; the danaparoid (DCI), marketed by ORGANON; ardeparin (DCI), developed by YETH AYERST; certoparin (DCI), marketed by SANDOZ and the products under study, such as CYO2 from SANOFI-CHOAY (Thromb Hae ostasis, 58 (1), 553 (1987 eL c-aipu-sto SF9Q107 / CR631540 efe SMCF1-CK3? > CN (T ropfo Haamstasis, 74, 1468-1473 (3995)) Preferably, the low molecular weight heparins are constituted of oligoaccharides having a 2-O-sulfo-4-enopyranosuronic acid at one of its ends. A particularly advantageous low molecular weight heparin is obtained by means of the depolymerization of an ester of heparin, by means of a base such as soda.The effect of low molecular weight heparins on the trauma of the central nervous system is demonstrated in the rat, on the trauma induced according to the following technique: the male rats of the Sprague-Dawley strain (Charles River France), weighing 280-300 g (13 for the control group and 13 for the treatment group) are anesthetized with halothane (1.5%) in a N20 / 02 (70/30) mixture and are placed adas in stereotactic tension. The epicranium is incised and an orifice is made by means of a toothed punch, at the level of the right parietal cortex (coordinates: 3.5 mm anterior to 6 mm above the interaural line). A polyethylene tube of 3 mm internal diameter is placed on the hard mother, is fixed in the cranial cavity with dental cement and is linked to a solenoid valve (Danfoss Evsi 24V, 15 W). The hard mother remains intact. The valve is connected to an HPLC pump (alters 590). The system is filled with sterile water and when the pump has reached a pressure of 3.8 to 4 bar, a fluid percussion of moderate severity (1.6 to 1.8 bar) is induced by a short opening of the valve (20 ms). The tube is removed immediately, the incision is sutured and the animals are returned to their cage in a room heated to a temperature of 26 to 28 ° C. Low molecular weight heparins, dissolved in saline (0.9% NaCl), are administered as follows: - 2 hours after the injury: 0.5 mg / kg / 5 mL IV bolus; - 2 hours 15 minutes after the injury: 1 mg / kg / 5 mL SC; 6 hours after the injury: 1 mg / kg / 5 mL SC; 24 hours after the injury: 1 mg / kg / 5 mL SC; and 30 hours after the injury: 1 mg / kg / 5 mL SC. 5 mL / kg of saline solution (0.9% NaCl) are administered to the control group under the same conditions.
The animals are sacrificed one week after the trauma and the size of the trauma is evaluated histologically. The coronal sections are colored with a mixture of hematoxylin / eosin and the areas of trauma are measured with an image analyzer. In this test, low molecular weight heparins reduced the size of the brain trauma by at least 40%. Enoxaparin (LOVENOXR) reduced the size of brain trauma by 50%. The medicaments are constituted by a salt (sodium or calcium, preferably) of a low molecular weight heparin in the form of a composition in which it is associated with any other pharmaceutically compatible product, which may be inert or physiologically active. The medicaments according to the invention can be used intravenously, subcutaneously, orally, rectally, topically or pulmonally (inhalation). Sterile compositions, for intravenous or subcutaneous administration, are generally aqueous solutions. These compositions may also contain adjuvants, in particular wetting agents, isotonic acids, emulsifiers, dispersants and stabilizers. The sterilization can be carried out in various ways, for example, by aseptic filtration, incorporating sterilizing agents into the composition; by irradiation. They can also be prepared in the form of sterile solid compositions, which can be dissolved in sterile water at the time of use, or any other sterile injectable medium. As solid compositions for oral administration, tablets, pills, powders (gelatin capsules, tablets) or granules can be used. In these compositions, the active principle is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon. These compositions may also comprise substances additional to the diluents, for example, one or more lubricants such as magnesium stearate or talc; an agent that favors oral absorption; a colorant; a wrap (dragees); or a varnish. As liquid compositions for oral administration, pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents, such as water, ethanol, glycerol, vegetable oils or paraffin oil can be used. These compositions may comprise substances additional to the diluents, for example, the humectants, sweeteners, thickeners, flavorings or stabilizers. Compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semi-synthetic glycerides, or psyethylene glycols.
The compositions for topical administration can be, for example, creams, lotions, eye drops, mouthwash, nasal drops or aerosols. The doses depend on the effect sought, the duration of the treatment and the route of administration used; they are generally between 0.2 mg and 4 mg per kg, per day, subcutaneously, either 14 to 280 mg per day, per adult. In general, the doctor will determine the appropriate dosage according to age, weight and any other factors appropriate to the subject to be treated. The present invention also concerns a method for the prevention or treatment of central nervous system trauma, and especially of spinal, cranial or cranial-spinal trauma, in man, which comprises the administration of an effective amount of a low heparin. molecular weight.
It is noted that, in relation to this date, the best method known by the applicant to carry out the aforementioned invention is the conventional one for the manufacture of the objects or substances to which it refers.
Claims (20)
1. The use of a low molecular weight heparin, characterized in that it is for the preparation of a drug useful for the prevention and treatment of central nervous system trauma.
2. The use, according to claim 1, characterized in that it is for the prevention and treatment of spinal trauma.
3. The use, in accordance with the rei indication 1, characterized because it is for the prevention and treatment of cranial trauma.
4. The use, according to claim 1, characterized in that it is for the prevention and treatment of cranio-spinal trauma.
5- The use, according to claim 1, characterized in that the low molecular weight heparin has an average molecular weight between 1,000 and 10,000 daltons.
6. The use, according to claim 1, characterized in that the low molecular weight heparin has an average molecular weight between 1,500 and 6,000 daltons.
7. The use, according to claim 1, characterized in that the low molecular weight heparin has an average molecular weight between 4,000 and 5,000 daltons.
8. The use, according to any of claims 1 to 4, characterized in that the low molecular weight heparin is constituted by oligosaccharides having a 2 -O-sulfo-4-enopyranosuronic acid at one of its ends.
9. The use, according to any of claims 1 to 5, characterized in that the low molecular weight heparin is obtained by means of depolymerization of an ester of heparin, by means of a base.
10. The use, according to any of the rei indications 1 to 7, characterized in that the low molecular weight heparin is enoxaparin (DCI).
11. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin is nadroparin (DCI).
12. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin I is parnaparin (DCI).
13. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin is reviparin (DCI).
14. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin is dalteparin (DCI).
15. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin is the tínzaparina (DCI).
16. The use, according to any of the rei indications 1 to 7, characterized in that the low molecular weight heparin is danaparoid (DCI).
17. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin is ardeparin (DCI).
18. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin is certoparin (DCI).
19. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin is the compound CY222.
20. The use, according to any of claims 1 to 7, characterized in that the low molecular weight heparin is the compound SR90107 / ORG31540.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR97/06550 | 1997-05-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA99010582A true MXPA99010582A (en) | 2000-09-04 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20140113652A (en) | Non anti-coagulative glycosaminoglycans comprising repeating disaccharide unit and their medical use | |
| AU752322B2 (en) | Use of low-molecular-weight heparins for preventing and treating central nervous system trauma | |
| AP619A (en) | Use of hyaluronic acid or salt for the treatment of a human having a stroke or myocardial infarction. | |
| US5767106A (en) | Treatment of disease and conditions associated with macrophage infiltration | |
| MXPA99010582A (en) | Use of low-molecular-weight heparins for preventing and treating central nervous system trauma | |
| US6579858B1 (en) | Use of low-molecular-weight heparins for the prevention and treatment of cerebral edemas | |
| CA2868403A1 (en) | Treatment of postpartum haemorrhage with chemically modified heparin or heparan sulphate and a uterotonic agent | |
| NZ517119A (en) | Use of low-molecular-weight heparins for preventing and treating central nervous system (CNS) trauma | |
| MXPA99010595A (en) | Use of low-molecular-weight heparins for preventing and treating cerebral edemas | |
| NZ212097A (en) | Parenteral pharmaceutical composition comprising metoclopramide (4-amino-5-chloro-n-((2-diethylamino) ethyl)-2-methoxybenzamide) and optionally sodium metabisulphite |