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Salmon Calcitonin (salmon + calcitonin)

Distribution by Scientific Domains

Medical Sciences	75%
Chemistry	25%

Selected Abstracts

Bioavailability and Biological Efficacy of a New Oral Formulation of Salmon Calcitonin in Healthy Volunteers,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2002
Thierry Buclin
Abstract Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 ,g of SCT orally, a placebo, and a 10-,g (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5,1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 ,g exceeding those of 10 ,g intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases. [source]

Effect of ipriflavone on pain due to recent osteoporotic vertebral crush fracture

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2002
Mohammad M. Rahman
Abstract Aim:,Ipriflavone conserves bone mass in postmenopausal osteoporosis. Salmon calcitonin and alendronate, two other anti-resorptive drugs, have been found to have analgesic effects in osteoporotic acute vertebral fracture. This study aimed to determine if ipriflavone also possesses such an effect. Methods:,Thirty-two women with recent osteoporotic vertebral fractures were randomly assigned to ipriflavone treatment or placebo groups. Ipriflavone was given at the dose of 200 mg three times a day. Non-steroidal anti-inflammatory drugs were given ad libitum in both groups. Calcium carbonate (1 g daily) was administered to all subjects. Intensity of pain at rest, on movement and on pressure, pain rating on a 10-point visual analogue scale, degree of mobility impairment, and supplementary analgesic were assessed at the end of a 3-month period in both groups to assess the analgesic effect of ipriflavone. Results:,Fourteen subjects in the ipriflavone group and 12 in the placebo group completed the trial. After 3 months, all pain variables had decreased significantly in both groups. Intensity of pain at rest and on pressure and supplementary analgesic use were significantly lower in the ipriflavone group compared to the placebo group. Conclusion:,The study shows that ipriflavone has an analgesic adjuvant effect in acute osteoporotic vertebral fracture. [source]

Bioavailability and Biological Efficacy of a New Oral Formulation of Salmon Calcitonin in Healthy Volunteers,

Direct Measurement of Hormone-Induced Acidification in Intact Bone

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2000
Glenn S. Belinsky
Abstract Previous findings have shown that osteoblasts respond to parathyroid hormone (PTH) with an increase in extracellular acidification rate (ECAR) in addition to the known effect of PTH to increase local acidification by osteoclasts. We, therefore, investigated use of the Cytosensor to measure the ECAR response of whole intact bone to PTH employing microphysiometry. The Cytosensor measures a generic metabolic increase of cells to various agents. Using neonatal mouse calvaria, we found that the area surrounding the sagittal suture was particularly responsive to PTH. In this bone, the increase in ECAR was slower to develop (6 minutes) and more persistent than in cultured human osteoblast-like SaOS-2 cells and was preceded by a brief decrease in ECAR Salmon calcitonin also produced an increase in ECAR in this tissue but with a different pattern than that elicited by PTH. Because PTH stimulates osteoclastic bone resorption in mouse calvaria via a cyclic adenosine monophosphate (cAMP)-mediated mechanism, we showed that the adenylyl cyclase activator forskolin also stimulated ECAR in this tissue. When the protein kinase A (PKA) pathway was activated by maintaining a high intracellular concentration of cAMP using N6 -2,-0-dibutyryladenosine-cAMP (db-cAMP), there was a reduction of PTH-induced acidification, while isobutylmethylxanthine pretreatment potentiated the PTH-induced acidification, consistent with a PKA-mediated pathway. Thapsigargin and the protein kinase C (PKC) activator phorbol myristate acetate had no effect on the PTH-induced increase in ECAR in calvaria, indicating that PKC does not play a major role in the ECAR response in intact bone. These results indicate the utility of using microphysiometry to study ECAR responses in intact tissue and should enable elucidation of the relative importance of extracellular acidification by osteoblasts and osteoclasts to the anabolic and catabolic activities of PTH, respectively. [source]

Synthesis, characterization and in vivo activity of salmon calcitonin coconjugated with lipid and polyethylene glycol

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2009
Weiqiang Cheng
Abstract An irreversible lipidized salmon calcitonin (sCT) analog, Mal-sCT, was previously shown to have comparable hypocalcemic activity to sCT in vivo. This study reports on the synthesis, characterization and pharmacological activity of novel PEGylated Mal-sCT analogs. Mal-sCT, prepared by conjugating sCT via thio-ether bonds with aqueous-soluble palmitic acid derivative at Cys 1 and Cys 7, was reacted with mPEG-succinimide (mPEG-Suc, 5 kDa). The products were purified and then identified by MALDI-TOF MS and HPLC. Mal-sCT was conjugated with 1 (1PEG-Mal-sCT) or 2 (2PEG-Mal-sCT) PEG chains at Lys 11 and Lys 18, the former being the preferred site of conjugation at higher mPEG-Suc/Mal-sCT ratio. Circular dichroism analysis showed the PEGylated Mal-sCT analogs to possess a robust helical conformation, while size measurement by dynamic light scattering indicated a propensity of the peptides to self-aggregate in aqueous solutions. Both 1PEG-Mal-sCT and 2PEG-Mal-sCT were more stable in rodent intestinal fluids than sCT or Mal-sCT. However, 1PEG-Mal-sCT had comparable hypocalcemic activity to Mal-sCT when injected subcutaneously in the rat, while 2PEG-Mal-sCT was inactive. 1PEG-Mal-sCT was inactive when administered orally in the rat. This study suggested PEGylation of Mal-sCT increased the stability of the lipidized peptide to enzyme degradation, but did not enhance its hypocalcemic activity. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1438,1451, 2009 [source]

Cytotoxicity evaluation of enzyme inhibitors and absorption enhancers in Caco-2 cells for oral delivery of salmon calcitonin

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2004
Rakhi B. Shah
Abstract The usefulness of enzyme inhibitors and absorption enhancers with least mucosal cell cytotoxicity was evaluated on Caco-2 cell monolayers. The temporal cytotoxicity of several protease inhibitors at 500 ,g/mL (e.g., turkey and chicken ovomucoids, aprotinin, and Protease Inhibitor Cocktail) and absorption enhancers [e.g., cholate (3%), glycocholate (3%), glycosursodeoxycholate (3%), ethylenediaminetetraacetic acid (EDTA, 0.1%), hydroxypropyl-,-cyclodextrin (HP-,-CD, 5%), hydroxypropyl-,-cylcodextrin (HP-,-CD, 5%), ,-cylcodextrin (,-CD, 5%), tetradecyl-,- D -maltoside (0.25%), octylglucoside (0.25%), citric acid (10%), glycyrrhetinic acid (0.34 mM), and Tween-80® (0.1%)] was measured by monitoring their effect on Caco-2 cell viability. Cell viability was measured by mannitol permeability measurements, transepithelial electrical resistance (TEER) measurements, DNA-propidium iodide staining assay, and WST-1 assay (tetrazolium salt based assay). Sodium dodecyl sulfate (0.1%), a potent surfactant, was used as a positive control. Chicken and turkey ovomucoids were nontoxic to cells as evaluated by all the methods used. Aprotinin decreased the TEER, whereas plasma membrane damage was seen with Protease Inhibitor Cocktail after a 24-h period. With respect to the absorption enhancers, the toxicity increased directly as a result of an increase in the time of incubation. The enhancers EDTA and HP-,-CD can be used safely for a short period of time, whereas glycosursodeoxycholate, glycyrrhetinic acid, octylglucoside, HP-,-CD, and ,-CD can be used for a longer period. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 1070,1082, 2004 [source]

Design, synthesis, characterization and in-vivo activity of a novel salmon calcitonin conjugate containing a novel PEG-lipid moiety

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2010
Weiqiang Cheng
Abstract Objectives The aim of the study was to explore (1) the synthesis of a novel poly(ethylene glycol) modified lipid (PEG-lipid, PL) containing a chemically active tri-block linker, ,-maleimido lysine (Mal), and its conjugation with salmon calcitonin (sCT), and (2) the biophysical properties and activity of the resulting conjugate, Mal-PL-sCT, relative to the control, 2PEG-Mal-sCT, which comprises sCT conjugated with ,-palmitoyl- N -,-maleimido- l -lysine at cysteine 1 and cysteine 7, and PEG moieties at lysine 11 and lysine 18 via a conventional stepwise method. Methods The PEG-lipid was obtained by condensing palmitic acid derivative of ,-maleimido lysine with methoxy poly(ethylene glycol) amine. Under reductive conditions, the PEG-lipid readily reacted with sCT to yield the resultant compound, Mal-PL-sCT. Key findings Dynamic light scattering analyses suggested that Mal-PL-sCT and 2PEG-Mal-sCT exhibited robust helical structures with a high tendency to aggregate in water. Both compounds were more stable against intestinal degradation than sCT, although Mal-PL-sCT was less stable than 2PEG-Mal-sCT. However, 2PEG-Mal-sCT did not possess hypocalcaemic activity while Mal-PL-sCT retained the hypocalcaemic activity of sCT when it was subcutaneously injected in the rat model. Multiple functional groups may be conjugated to a peptide via a tri-block linker without the risk of obliterating the intrinsic bioactivity of the peptide. Conclusions The resultant novel PEG-lipid has a potential role to optimize protein and peptide delivery. [source]

Effect of chitosan on the intranasal absorption of salmon calcitonin in sheep

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2005
Michael Hinchcliffe
The effects of a chitosan-based delivery system on the pharmacokinetics of intranasally administered salmon calcitonin (sCT) were investigated in a sheep model. In particular, the feasibility of producing a formulation with a comparable or improved bioavailability and/or less variability than the currently marketed nasal product (Miacalcin nasal spray, Novartis Pharmaceuticals) was assessed. A comparator (control) formulation comprising sCT solution was also tested. Sheep (n = 6) were dosed intranasally according to a randomized crossover design. The intranasal sCT dose was 1100 IU (equivalent to approximately 17 IU kg,1). After completion of the nasal dosing legs, five of the sheep received 300 IU sCT (equivalent to approximately 5 IU kg,1) by subcutaneous injection to estimate relative bioavailability. After intranasal or subcutaneous dosing, serial blood samples were taken and plasma separated by centrifugation before measuring sCT concentrations by ELISA. Pharmacokinetic (non-compartmental) and statistical (analysis of variance or non-parametric alternative) analyses were performed. No systemic or local adverse effects were observed following intranasal or subcutaneous administration of sCT. The mean relative bioavailability of sCT from the chitosan solution was improved twofold compared with Miacalcin nasal spray and threefold compared with sCT control solution. Inter-animal variability in sCT absorption appeared to be lower with use of the chitosan-based solution compared with the control solution or commercial product. Based on the reported sheep data, a chitosan delivery system could offer the potential to significantly improve the intranasal absorption of sCT and reduce the variability in absorption. In the clinical setting, this may allow relatively lower doses of the drug to be given intranasally and/or lead to improvements in the efficacy or quality of intranasal therapy. [source]

Gelatin Microspheres as a Pulmonary Delivery System: Evaluation of Salmon Calcitonin Absorption

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2000
KAZUHIRO MORIMOTO
The use of negatively and positively charged gelatin microspheres for pulmonary delivery of salmon calcitonin was examined in rats. The microspheres were prepared using acidic gelatin (isoelectric point (IEP):, 5.0) and basic gelatin (IEP, 9.0) for the negatively and positively charged microspheres, respectively. The average diameters of positively charged gelatin microspheres in the dry state were 3.4, 11.2, 22.5 and 71.5 ,m, and that of negatively charged gelatin microspheres was 10.9 ,m. Neither positively nor negatively charged gelatin microspheres underwent any degradation in pH 7.0 PBS and there was less than 8% degradation in bronchoalveolar lavage fluid (BALF) after 8 h. In in-vitro release studies in pH 7.0 PBS, salmon calcitonin was rapidly released from positively charged gelatin microspheres within 2 h, and its cumulative release was approximately 85%. In addition, the release profiles were not influenced by particle sizes. The release rates of salmon calcitonin from negatively charged gelatin microspheres were lower than that from positively charged gelatin microspheres. The cumulative release was approximately 40% after 2 h, but there was no evidence of any sustained release. The pulmonary absorption of salmon calcitonin from gelatin microspheres was estimated by measuring its hypocalcaemic effect in rats. The pharmacological availability after administration of salmon calcitonin in positively and negatively charged gelatin microspheres was significantly higher than that in pH 7.0 PBS. The pharmacological availability after administration of salmon calcitonin in positively charged gelatin microspheres was significantly higher than that in negatively charged gelatin microspheres. Administration of salmon calcitonin in positively charged gelatin microspheres with smaller particle sizes led to a higher pharmacological availability. The pharmacological availability after pulmonary administration of salmon calcitonin in positively charged gelatin microspheres with particle sizes of 3.4 and 11.2 ,m was approximately 50%. In conclusion, the gelatin microspheres have been shown to be a useful vehicle for pulmonary delivery of salmon calcitonin. [source]

Influence of calcitonin administration on ultimobranchial and parathyroid glands of pigeon, Columba livia

MICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2009
Seema Yadav
Abstract Pigeons were divided into two numerically equal groups (A and B) containing 30 specimens each. Birds from group A were intraperitoneally injected daily with 0.1 mL/100 g body wt of vehicle (0.1 M acetate buffer, pH 4.3 containing 0.1% gelatin). Specimens from group B were intraperitoneally injected daily with 1 ,g/100 g body wt of salmon calcitonin. Six birds were sacrificed from each group 2 h after the last injection on 1st, 3rd, 5th, 10th, and 15th day of the experiment. After collection of blood samples, ultimobranchial and parathyroid glands were fixed for histological studies. In calcitonin-treated C. livia, the plasma calcium levels exhibit a progressive decline from day 1 till day 5. On day 15, the levels become more or less similar to the control value. No change has been noticed on day 1 in the plasma phosphate levels of calcitonin-treated C. livia. The levels decrease progressively from day 3 to day 5; thereafter, it exhibits an elevation so that on day 15, normal plasma phosphate levels is achieved. The ultimobranchial gland of C. livia exhibits no change up to day 5 following calcitonin treatment. The nuclear volume of ultimobranchial cells exhibits a decrease on day 10. This response progresses up to day 15. Few degenerating cells are also discerned following 15 days calcitonin treatment. The parathyroid gland of calcitonin-treated C. livia exhibits no histological alteration up to day 3. The nuclear volume of parathyroidal cells exhibits a progressive increase from day 3 till the close of the experiment (day 15). Moreover, the gland exhibits more compactness on day 10 and day 15. Few degenerating cells are encountered after day 15 following calcitonin treatment. Microsc. Res. Tech. 2009. © 2008 Wiley-Liss, Inc. [source]

Oral salmon calcitonin reduces Lequesne's algofunctional index scores and decreases urinary and serum levels of biomarkers of joint metabolism in knee osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 10 2006
Daniel-Henri Manicourt
Objective To evaluate the effects of oral salmon calcitonin (sCT) on Lequesne's algofunctional index scores and on biomarkers of joint metabolism in knee osteoarthritis. Methods In this randomized, double-blind trial, patients received either placebo (n = 18), 0.5 mg of sCT (n = 17), or 1 mg of sCT (n = 18) daily for 84 days. Biomarkers included C-telopeptide of type II collagen (CTX-II), type II collagen neoepitope C2C, collagenases (matrix metalloproteinase 1 [MMP-1], MMP-8, and MMP-13), stromelysin (MMP-3), tissue inhibitors of metalloproteinases 1 and 2, and hyaluronan. Statistical analysis included nonparametric tests. Results A total of 41 patients completed the study (13 in the group receiving 0.5 mg of sCT and 14 in each of the other 2 other groups). Although, on day 84, patients in both the placebo group and the group receiving 1 mg of sCT exhibited a similar significant decrease in pain scores, a significant reduction in the function score was observed only in the 2 sCT groups. On day 84, there was no significant decrease in biomarker levels in the placebo group, whereas significant reductions in the levels of both MMP-3 and hyaluronan were observed in the 2 sCT groups. The group of patients receiving 1 mg of sCT exhibited significant decreases in the levels of CTX-II, C2C, and MMP-13. Conclusion By improving functional disability and by reducing levels of biomarkers that are thought to be predictive of joint space narrowing (and thus cartilage loss), oral sCT at a dose of 1 mg might be a useful pharmacologic agent in human knee OA. [source]

Novel Secondary Structure of Calcitonin in Solid State as Revealed by Circular Dichroism Spectroscopy

CHINESE JOURNAL OF CHEMISTRY, Issue 7 2002
Hai-Ning Du
Abstract The solid-state circular dichroic study reveals that salmon calcitonin presents a typical ,-helical structure while human calcitonin appears to form a ,-sheet in solid state, although both of them adopt random coil structures in aqueous solution. [source]