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  • 1
    Electronic Resource
    Electronic Resource
    Clinical and microbiological effects of sustained release chlorhexidine in periodontal pockets (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of clinical periodontology 13 (1986), S. 0 
    Details
    ISSN: 1600-051X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract Previous studies have shown that a 3-day exposure of the pocket flora to the sustained release of chlorhexidine significantly reduced the relative numbers of spirochetes and motile rods in periodontal pockets to negligible amounts. By 14 days post-treatment, their numbers had returned to pre-treatment levels. The present study extended the exposure time of the pocket flora to the sustatined release of chlorhexidine in an attempt to prolong the suppression of the microbial flora for a clinically significant period of time. Clinical parameters were also studied. Sustained release devices (SRD) were inserted into 13 pockets from 8 patients. Pocket depth ranged between 5 and 8 mm. The SRD's were replaced every 3 days to give a total exposure of 9 days. Plaque index (P1I). bleeding on probing and pocket depth were measured, and bacterial samples taken for dark field microscopy and anaerobic culture.There was a marked decrease in the relative proportions of spirochetes and motile rods and the total anaerobic count post-treatment. Pocket depth was reduced in all 13 pockets. These results indicate that a prolonged exposure to chlorhexidine suppresses the pocket flora to negligible amounts and reduces pocket depth for up to 11 weeks post-treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-051X.1986.tb00882.x
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  • 2
    Electronic Resource
    Electronic Resource
    New sustained release dosage form of chlorhexidine for dental use (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of periodontal research 17 (1982), S. 0 
    Details
    ISSN: 1600-0765
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The purpose of this study was to develop a sustained release dosage form of chlorhexidine diacetate for topical use. Cast films of ethyl cellulose with or without polyethylene glycol containing 5, 10, and 20 % of the drug were prepared and exhibited sustained release. Chloroform and ethanol were used as casting solvents. Release rate of chlorhexidine from the film was measured by means of a UV spectrophotometer, and kinetics of release were found to conform to Higuchi's diffusional model. This study demonstrates that by embedding chlorhexidine in polymeric films it is possible to obtain sustained release of the drug for several months.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0765.1982.tb01160.x
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  • 3
    Electronic Resource
    Electronic Resource
    A New Route of Drug Administration: Intrauterine Delivery of Insulin and Calcitonin (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 828-833 
    Details
    ISSN: 1573-904X
    Keywords: drug administration ; drug delivery ; absorption ; controlled release ; drug implants ; peptides ; intrauterine ; calcitonin ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract High molecular weight drugs in general, and peptides in particular, are usually delivered by parenteral route because they are poorly absorbed or degraded in the gastrointestinal tract. To optimize therapy, it is desirable to search for nonparenteral routes of administration and to deliver the drug in a controlled-release fashion. We report here on the absorption and the systemic biological effect of two peptides, insulin and calcitonin, after instillation into the uterus of the rat. Intrauterine delivery was compared to subcutaneous injections in intact and ovariectomized rats. In addition, we describe results of a preliminary study on calcitonin absorption from controlled-release matrices inserted in the rat uterus. The amount and duration of the hypoglycemic and the hypocalcemic effects induced by intrauterine delivery of insulin and calcitonin, respectively, were equivalent to those obtained after subcutaneous injections. The results were similar in intact and ovariectomized rats. It is concluded that the intrauterine administration of both insulin and calcitonin is bioequivalent to subcutaneous injection. The therapy of a number of clinically important diseases could benefit from this discovery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018948924992
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  • 4
    Electronic Resource
    Electronic Resource
    Bisphosphonates and Tetracycline: Experimental Models for Their Evaluation in Calcium-Related Disorders (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 606-613 
    Details
    ISSN: 1573-904X
    Keywords: bisphosphonates ; tetracycline ; calcification ; hydroxyapatite ; bone resorption ; synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This work was aimed at synthesizing novel bisphosphonates (BPs) and examining them in comparison to clinically used BPs such as pamidronate and alendronate, and to tetracycline, in order to evaluate their potential as anticalcification and antiresorption agents. The correlation between the various models was examined in order to establish facile experimental models for pre-screening of potential compounds. Methods. Nitrogen-containing heterocyclic, novel BPs such as 2-(3-methylimidazolio) ethylidene-l,l-bisphosphonic acid betaine (VS-5b), 2-(2-dimethylamino-4-pyrazinio)ethylidene-1,1 -bisphosphonic acid betaine (VS-6b), and 2-(2-α-pyridylethylthio) ethylidene-1,1-bisphosphonic acid (ISA-225), were synthesized and evaluated in comparison to clinically used BPs, in various experimental models of resorption and calcification. Results. The physicochemical properties of the novel compounds are slightly different than the BPs in clinical use: the pKa values are lower, the affinity for hydroxyapatite is lower and the solubilities of the calcium salts are higher. The anticalcification potencies of the novel compounds were high and ranked as follows: alendronate = pamidronate 〉 VS-6b = VS-5b = ISA-225 〉 tetracycline. The in vivo antiresorption activity of VS-5b and VS-6b in comparison to that of the clinically employed, pamidronate, was shown to be similar and higher, respectively. Conclusions. The anticalcification activity of the novel compounds as well as that of tetracycline was lower than that of alendronate. The antiresorption activity of VS-6b was similar to that of pamidronate. A good correlation between the different models was found, enabling the facile screening of novel compounds. The activities of tetracycline and EDTA highlight the distinct behavior of BPs as "crystal poison”. In addition, tetracycline was found to be a potent anticalcification agent in the ectopic calcification model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011990129437
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  • 5
    Electronic Resource
    Electronic Resource
    Synthesis and Preclinical Pharmacology of 2-(2-Aminopyrimidinio) Ethylidene-1,1-Bisphosphonic Acid Betaine (ISA-13-1)-A Novel Bisphosphonate (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1399-1406 
    Details
    ISSN: 1573-904X
    Keywords: bisphosphonates (diphosphonates) ; calcium-related disorders ; bone-related disorders ; drug administration ; drug absorption tight junctions ; mannitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To validate our hypothesis that a bisphosphonate (BP) having a nitrogen-containing heterocyclic ring on the side chain, and with no hydroxyl on the geminal carbon would possess increased activity, and better oral bioavailability due to enhanced solubility of its calcium complexes/salts and weaker Ca chelating properties. Methods. A novel BP, 2-(2-aminopyrimidinio)ethylidene-l,l-bisphosphonic acid betaine (ISA-13-1) was synthesized. The physicochemical properties and permeability were studied in vitro. The effects on macrophages, bone resorption (young growing rat model), and tumor-induced osteolysis (Walker carcinosarcoma) were studied in comparison to clinically used BPs. Results. The solubility of the Ca salt of ISA-13-1 was higher, and the log βCa: BP stability constant and the affinity to hydroxyapatite were lower than those of alendronate and pamidronate. ISA-13-1 exhibited effects similar to those of alendronate on bone volume, on bone osteolysis, and on macrophages, following delivery by liposomes. ISA-13-1 was shown to have 1.5−1.7 times better oral absorption than the other BPs with no deleterious effects on the tight junctions of intestinal tissue. Conclusions. The similar potency to clinically used BPs, the increased oral absorption as well as the lack of effect on tissue tight junction of ISA-13-1 warrant its further consideration as a potential drug for bone diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018951025493
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  • 6
    Electronic Resource
    Electronic Resource
    Measurement of Serum [3H]Tetracycline Kinetics and Indices of Kidney Function Facilitate Study of the Activity and Toxic Effects of Bisphosphonates in Bone Resorption (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 1018-1023 
    Details
    ISSN: 1573-904X
    Keywords: bisphosphonates (diphosphonates) ; bisacylphosphonates ; bone resorption ; tetracycline ; mineralization ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The [3H]tetracycline ([3H]TC) model is based on the observation that TC is released from the bones of rats prelabeled with [3H]TC via first-order kinetics, a factor directly reflecting the kinetics of bone resorption. In the present paper we applied the [3H]TC elimination model to rats treated with antiresorptive drugs. The validity of this model was evaluated by examining the effect of the bisphosphonate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (ABP), and a novel bisphosphonate, dihydrogen disodium adipoylbisphosphonate (AdBP), on serum TC levels and the elimination rate constant. ABP and AdBP significantly inhibited the TC elimination rate. However, ABP treatment caused impairment of bone mineralization, renal dysfunction, and inhibition of somatic growth. It is concluded that antiresorptive effects of bisphosphonates could be evaluated by the [3H]TC model, but this model is limited to animals with normal kidney function. The experimental conditions provide a technically simple method which is sensitive enough to examine antiresorptive properties in a healthy animal and to detect adverse effects on the kidney. The activity of the novel bisacylphosphonate, AdBP, and lack of its adverse effects indicate the potential of this drug for clinical applications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015898226519
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  • 7
    Electronic Resource
    Electronic Resource
    Bisacylphosphonates Inhibit Hydroxyapatite Formation and Dissolution in Vitro and Dystrophic Calcification in Vivo (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 143-148 
    Details
    ISSN: 1573-904X
    Keywords: bisphosphonates ; phosphonates ; acylphosphonates ; ketophosphonates ; calcification ; calcinosis ; hydroxy apatite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Some geminal bisphosphonates are used clinically for a number of important bone/calcium related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bisacylphosphonates (e.g., adipoyl- and suberoylbisphosphonate). These compounds were found to inhibit significantly hydroxyapatite formation and dissolution in vitro and the calcification of bioprosthetic tissue implanted subdermally in rats. These are the first instances of nongeminal bisphosphonates [P–(C)n– P, n ≥ 2] that have been reported to be active in calcium-related disorders. The reported bisacylphosphonates possess apparent lower toxicity, and their calcium complexes/salts have improved solubility properties. Therefore, they are of potential importance for clinical applications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018956516640
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  • 8
    Electronic Resource
    Electronic Resource
    Controlled release of bisphosphonate from a biodegradable implant: Evaluation of release kinetics and anticalcification effect (1992)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Biomaterials 3 (1992), S. 23-28 
    Details
    ISSN: 1045-4861
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The present investigation describes the formulation and the in vivo efficacy of prolonged controlled-release chitosan matrices, containing the novel anticalcification agents adipoyland suberoylbisphosphonate (AdBP and SuBP). Chitosan matrices were prepared by the solvent-cast method and the role of several factors such as polymer molecular weight (MW), crosslinking, and drug load concentration, on the release rate profile have been examined. Crosslinking of chitosan films retarded degradation rate of the polymer but not the release rate of the embedded drug. Chitosan's MW and drug load concentration did not affect drug release rate. The release kinetics of the bisacylphosphonates were characterized by initial burst-effect and pseudo zero-order kinetics in the following release phase. AdBP/chitosan matrices (co-implanted subdermally in rats with the calcifiable bioprosthetic heart valve tissue) significantly inhibited tissue calcification after 15 and 30 days implantation (66.4 and 108.6 μg/mg Ca++ in comparison to 2.7 and 3.6 μg/mg Ca++, untreated and treated groups, respectively). No side effects were noted.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jab.770030105
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  • 9
    Electronic Resource
    Electronic Resource
    Structurally different bisphosphonates exert opposing effects on alkaline phosphatase and mineralization in marrow osteoprogenitors (1998)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 68 (1998), S. 186-194 
    Details
    ISSN: 0730-2312
    Keywords: osteoprogenitors ; marrow-stroma ; alkaline phosphatase ; bisphosphonates ; cell proliferation ; mineralization ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Bisphosphonates (BPs) are inhibitors of bone resorption and soft tissue calcification. The biological effects of the BPs in calcium-related disorders are attributed mainly to their incorporation in bone, enabling direct interaction with osteoclasts and/or osteoblasts through a variety of biochemical pathways. Structural differences account for the considerable differences in the pharmacological activity of BPs. We compared the effects of two structurally different compounds, alendronate and 2-(3′-dimethylaminopyrazinio)ethylidene-1,1-bisphosphonic acid betaine (VS-6), in an osteoprogenitor differentiation system. The BPs were examined in a bone marrow stromal-cell culture system, which normally results in osteoprogenitor differentiation. The drugs were present in the cultures from days 2 to 11 of osteogenic stimulation, a period estimated as being comparable to the end of proliferation and the matrix-maturation stages. We found that the two different BPs have opposing effects on specific alkaline phosphatase (ALP) activity, on stromal-cell proliferation, and on cell-mediated mineralization. These BPs differentially interact with cell-associated phosphohydrolysis, particularly at a concentration of 10-2 of ALP Km, in which alendronate inhibits whereas VS-6 did not inhibit phosphatase activity. VS-6 treatment resulted in similar and significantly increased mineralization at 10 and 1 μM drug concentrations, respectively. In contrast, mineralization was similar to control, and significantly decreased at 10 and 1 μM drug concentrations, respectively, under alendronate treatment. J. Cell. Biochem. 68:186-194, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Prevention of bioprosthetic heart valve tissue calcification by charge modification: Effects of protamine binding by formaldehyde3 (1991)
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 25 (1991), S. 85-98 
    Details
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Calcification is the principal cause of the clinical failure of bioprosthetic heart valves (BHV). Calcification occurs through an interaction of host and implant factors, mainly younger age and glutaraldehyde pretreatment, respectively. The hypothesis of this work was that an impaired balance between positively and negatively charged amino acids, due to the reaction with Lys and Hyl tissue-collagen residues, expose affinity sites to Ca++. We further hypothesized that regardless of the cause(s) of BHV calcification, positive charge modification of the tissues will prevent their propensity to calcify. Modification of BHV tissue was obtained by covalently binding protamine sulfate, a polybasic peptide, via formaldehyde and subsequent glutaraldehyde tissue crosslinking. Protamine-bound tissue exhibited stability properties (shrinkage temperature and resistance to collagenase digestion) similar to BHV tissue. Protamine-treated tissue was less permeable to Ca++, and reduced staining was observed with positively charged dyes, indicating the presence of positively charged functional groups in the modified tissue. Significant prevention of calcification was exhibited by the p-bound tissue in comparison to BHV tissue, 30.9 and 109 μg/mg calcium, respectively, after 30 days of subdermal implants in rats. The modification procedure resulted in stable, covalent links of approximately 10% w/w protamine with undiminished anticalcification properties, even after 1 year storage. The results support our hypotheses, and orthotopical heart valve replacements are required in order to completely evaluate the treatment efficacy and bio-compatibility.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jbm.820250107
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