| 摘要 |
<p>#CMT# #/CMT# Biocompatible polymers having a molecular weight of at least 5000, comprising polymerized monomer with carboxyl and sulfate or sulfonate groups. #CMT# : #/CMT# The new polymers are of formula (I) A a-X x-Y y (I) A : a monomer; X : a carboxyl group fixed on monomer A and of formula R-COO-R'; R : a bond or aliphatic hydrocarbon chain which may be branched and/or unsaturated and which may contain one or more aromatic rings, other than benzylamine and benzylamine sulfonate; R' : H or a cation; Y : a sulfate or sulfonate group fixed on to A and of formula -R-O-SO 3-R', -R-N-SO 3-R'- or -R-SO 3-R'-; a : the number of units of monomer A, and is such as to give (I) a molecular weight of at least 5000; x : the degree of substitution of all monomers A by groups X and is 20 - 150%, preferably around 50%; y : the degree of substitution of all monomers A by groups Y and is 30 - 150%, preferably around 100% Preferably the monomers A are sugars, esters, alcohols, amino acids or nucleotides, glucose units being especially preferred. The groups R are preferably straight or branched alkyl, allyl, or aryl groups. The polymers may further contain groups Z, which are different to X and Y and which confer supplementary biological or physicochemical properties on the polymer, such as increased solubility or lipophilicity. Suitable such groups Z include amino acids, fatty acids and alcohols, ceramides, and nucleotide sequences. #CMT#USE : #/CMT# The polymers are regenerating agents, useful in therapy and diagnosis. The compounds may have any of the following actions: stabilizing and potentiating growth factors having an affinity for heparin, inhibiting proteases present in inflammatory processes, prevention and treatment of lesions and pain in tissues and organs, prevention and treatment of lesions in muscular, nervous and digestive tract tissues, cicatrization of cutaneous, corneal, flat bone and long bone tissues. In addition the polymers act to regenerate, protect, and age tissue and cells in vivo and ex vivo. In combination with superoxide dismutase the polymers may be used to prevent and treat the deleterious effects of ischemias, ionizing radiation, and oxidant products induced by pathologies, stress, or carried in the diet. They may be used to prevent and treat pathologies associated with hypnoxia, cellular degeneration, myopathias, hepatopathias, nephropathias, cardiopathias, and molecular peroxidation, cardiac and nervous disorders, anarchic cell growth and pathologies associated with angiogenesis. They may also be used in the conservation of tissues, organs and prostheses, in the prevention and treatment of pulmonary, renal, hepatic, cardiac, vascular, and dermatological pathologies, to aid the functional assimilation of grafts, to prevent oxidative stress and lesions etc. due to oxidizing agents, for the treatment of aging factors, the effects of diabetes, the treatment of leprosy, endotoxic shock, the effects of attack by pathogenic agents such as viral, microbial, parasitic agents and prions, as an adjunct to radiotherapy in the treatment of cancers, and for the treatment of hypertension. #CMT#ADVANTAGE : #/CMT# The polymers are easy to prepare and have a similar action to HBGFPP (heparin-binding growth factor protector and potentiator) but have a much broader field of application than the latter. #CMT#PHARMACEUTICALS : #/CMT# The polymers may be formulated with any pharmaceutically-acceptable vehicle for administration locally, intravenously, intra-arterially, intramuscularly, intra-peritoneally, intra-ocularly, into the cerebrospinal fluid or directly into the central nervous system, orally, percutaneously, subcutaneously, topically, and into all liquid-containing parts of the body. #CMT#ADMINISTRATION : #/CMT# The oral daily dose is 1 - 5000 mg/kg, the intramuscular dose is 0.2 - 500 mg/kg, and for intraperitoneal or intra-ocular use, or for administration into the cerebrospinal fluid or intracochlear fluid the daily dosage is 0.1 - 100 mg/kg. #CMT#EXAMPLE : #/CMT# A dextran of molecular weight 40,000 (37.37g) was dissolved in water (182 ml) and treated with sodium hydroxide (74g) in water (124 ml) at 4[deg]C. Monochloroacetic acid (76.2g) was added slowly keeping the temperature at 4 [deg]C, then it was allowed to rise to 21[deg]C. The mixture was then heated at 50 [deg]C for 40 minutes, cooled and neutralized with acetic acid. The carboxymethyl dextran formed was recovered by precipitation with ethanol, dried, ultrafiltered and lyophilized. This product (500 mg) was dispersed in dichloromethane (40 ml) and chlorosulfonic acid (0.5g) in dichloromethane (4 ml) was added. The resultant sulfated carboxymethyl dextran was filtered off.</p> |
