SEARCH · PubMed Health

Results for “beta-Cyclodextrins”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed1992

Chemical modification of cyclomaltodextrin glucanotransferase from Bacillus circulans var. alkalophilus.

Counting of integral numbers of cysteine residues of the reduced and denaturated form of cyclomaltodextrin glucanotransferase (CGTase) from Bacillus circulans var. alkalophilus (ATCC 21783) showed two cysteine residues per enzyme molecule. Titrations of the enzyme with 5,5'-dithiobis-(2-nitrobenzoic acid) led to the same result. No free SH-group was detected in denatured form of CGTase, indicating that the two cysteine residues are linked by one disulfide bridge. Cyclizing activity of the GdmCl-denaturated and reduced enzyme was 13% of that of the native one. Incubation of CGTase with diethylpyrocarbonate (DEP) showed a pseudo-first-order inhibition with second-order rate constant of 3.2 M-1 s-1. Reaction with hydroxylamine and spectroscopic studies implied that inactivation of CGTase by DEP is due to modification of one histidine residue concomitantly with a 50% decrease in the cyclizing activity (t1/2 = 10.8 min). The inhibition was partially reversible. CGTase was protected against inactivation by alpha- and beta-cyclodextrins suggesting that the modified histidine residue is at or near the active site. Conversion of starch with DEP-modified enzyme resulted in a decreased formation of cyclodextrins while the relative amount of reducing sugars increased. Preliminary results on modification of CGTase with other reagents, e.g., Woodward's reagent K, 2,3-butanedione and carbodiimide are included.

Cysteine↗

PubMedDate not supplied

The determination of the geometric isomers and related impurities of dothiepin in a pharmaceutical preparation by capillary electrophoresis.

The application of capillary zone electrophoresis in the assay of the tricyclic antidepressant drug, dothiepin, in tablets is discussed. The method developed for dothiepin which exists as the cis- and trans-isomers and contains two major related impurities, an 11-oxo compound and a propanamine, utilizes inclusion complexation with beta-cyclodextrin. For optimization of the method the structured procedure of factorial design was used; the electrolyte solution was 50 mM disodium hydrogen phosphate with 10 mM beta-cyclodextrin-propan-1-ol(90:10, v/v). Good precision (RSD = 1.06%, n = 6), linearity (y = 26.84x + 2.25), and correlation (r = 0.999, n = 7) was obtained for trans-dothiepin. The reproducibility of tablet extraction was also acceptable (RSD = 0.77%, n = 6); the recovery of the trans-isomer was 98% (w/w) and the level of cis-isomer in tablets of dothiepin (75 mg) was 5.58% (w/w).

Cyclodextrins↗

PubMedDate not supplied

Evaluation of six chiral stationary phases in LC for their selectivity towards drug enantiomers.

Six chiral stationary phases (CSP) were evaluated for their enantioselectivity towards a series of 45 drugs with different acidic, basic or neutral properties. These CSPs were: a polyacrylamide phase, Chiraspher; two polysaccharide-based phases, cellulose tris-3,5-dimethyl phenylcarbamate (Chiralcel OD) and the S-naphthylethylcarbamate derivative of beta-cyclodextrin (SN-beta-CD; Cyclobond I SN); and three protein-based CSPs--alpha 1-acid glycoprotein (Chiral-AGP), ovomucoid (OVM) and cellulase. A total of 28 different mobile phases were involved. Chiral-AGP, OVM and Chiralcel OD appeared to be the most promising CSPs for the enantio separation of the series of structurally different compounds evaluated. Cellulase and Chiralcel OD show particularly high enantioselectivity towards the group of beta-blocker drugs. The different protein-based CSPs were used in their usual reversed-phase mode. The other phases were used in combination with apolar mobile phases, except for SN-beta-CD, which was evaluated in both modes. Formal optimization strategies were not adopted, although the effect of organic modifier and eluent pH on enantioselectivity was briefly examined for the protein-based phases.

Adrenergic beta-Antagonists↗

PubMed1976

Comb-like derivatives of amylose having (1-6)-linked malto-oligosaccharide side-chains.

The preparation of acetylated glycosyl bromide derivatives of the higher malto-oligosaccharides was studied by using beta-cyclodextrin or linear malto-oligosaccharides of d.p. 6 and 7. The products were treated with 2,3-di-O-phenylcarbamoyl-6O-tritylamylose in the presence of silver perchlorate (reaction A), and with 2,3-di-O-phenylcarbamoylamylose in the presence of mercuric cyanide and mercuric bromide (reaction B). After removal of the substituents, the branched molecules were characterized by their iodine-binding properties, beta-amylolytic degradation, and their priming activity in phosphorolytic synthesis. The distance between the branch points of the backbone chain was 25-55 and 100-150 units in the products from reactions A and B, respectively. Thus, the frequency of branching was considerably lower than in the comb-like molecules having D-glucose side-chains previously described.

Binding Sites↗

PubMed1977

Evidence for intermediate formation in the mechanism of potato starch -hosphorylase from exchange of the ester and phosphoryl oxygens of alpha-D-glucopyranose 1-phosphate.

We have examined under a variety of conditions the ability of potato starch phosphorylase to cause exchange of the ester and phosphoryl oxygens of alpha-D-glucopyranose 1-phosphate (Glc-1-P). In the presence of phosphorylase and strach, under conditions where 40-50% of the glc-1-P is consumed in starch elongation, little if any exchange occurs that cannot be accounted for by accompanying starch phosphorolysis. Nor are the oxygens scrambled in the same or longer times by enzyme only when no release of inorganic phosphate occurs. But when D-maltotriose is used as a primer, or during primerless synthesis, and in the presence of phosphorylase and alpha- or beta-cyclodextrin, a large degree of scrambling does occur. We conclude that under these latter conditions a glucosyl cation or covalent glycosyl-enzyme intermediate in formed. If this same intermediate is formed in the absence of starch or its analogue, then the phosphate counterion is not free to rotate; if the intermediate is formed with starch, then again one must assume that the rotation of phosphate ion is hindered, or that formation of the intermediate is rate determining.

Alkaline Phosphatase↗

PubMed1975

Reversible inhibition of the fatty acid synthetase complex from Mycobacterium smegmatis by palmitoyl-coenzyme A.

Palmitoyl-CoA dissociates the fatty acid synthetase complex from Mycobacterium smegmatis into inactive subunits of molecular weight 250,000 as determined by sucrose density gradient centrifugation. Palmitoyl-CoA binds to the subunits but the binding can be prevented and reversed by the mycobacterial 3-O-methylmannose-containing polysaccharide. When the palmitoyl-CoA containing inactive subunits were isolated by gel filtration on Sepharose 6B, and then concentrated and dialyzed against 0.5 M phosphate buffer, pH 7.0, containing 3 mM of the complexing agent heptakis-(2,6-di-O-methyl)-beta-cyclodextrin, activity was regenerated to the level of 40 percent of a control sample. The reversibility of the dissociation and inactivation of the synthetase by palmitoyl-CoA suggests that this end product might play a regulatory role by acting as a feedback inhibitor.

Coenzyme A↗

PubMed1976

Cyclodextrin nephrosis in the rat.

The renal toxicity of the Schardinger dextrins, alpha and beta-cyclodextrin, is manifested as a series of alterations in the vacuolar organelles of the proximal convoluted tubule. These changes begin as an increase of apical vacuoles and the appearance of giant lysosomes. The giant lysosomes characteristic of cyclodextrin nephrosis are notable because of the prominent acicular microcrystals embedded in the lysosomal matrix. Giant vacuoles devoid of acid phosphatase reaction product are found in advanced lesions. The vacuolar apparatus shows advanced changes prior to manifestation of lesions in mitochondria and other organelles. These observations indicate a role of the vacuologenic apparatus in the nephrotic process. Intracellular concentration of toxin via the lysosomal pathway represents a perversion of the physiologic function of the proximal tubule which ultimately leads to cell death.

Animals↗

PubMed1976

Studies on the fatty acid inactivation of phosphofructokinase.

Investigation of phosphofructokinase in normal and regenerating livers led to the discovery of an inactivating factor in the extracts of these livers. The inactivating factor was found to be a mixture of free fatty acids. The fatty acid compositions of the normal and regenerating livers are the same, but the concentrations of most of the fatty acids are at least 3 to 4 times higher in the latter. Inactivation of phosphofructokinase by palmitate and oleate was investigated using purified rabbit muscle enzyme. Incubation of the enzyme with palmitate (250 muM) or oleate (50 muM) resulted in rapid inactivation of the enzyme with biphasic curves. The concentrations of oleate and palmitate required to produce 50% inactivation of the enzyme were 35 muM and 75 muM, respectively. Fructose-6-P (0.5 mM), MgATP, (1 mM), fructose-1,6-P2 (1 mM), AMP (1 mM), and cyclic adenosine 3':5'-monophosphate (20 muM) protected the enzyme against inactivation when these metabolites were incubated with the enzyme before the addition of fatty acid. Bovine serum albumin (100 muM) and beta-cyclodextrin (0.25 mM) also protected the enzyme against the inactivation. However, if the enzyme was inactivated by fatty acid, subsequent addition of the above metabolites or bovine serum albumin did not reactivate the enzyme. Binding studies with [3H]oleate revealed at least three types of binding sites. The first site binds 2 to 4 mol of oleate/mol of enzyme. Oleate binding to this site did not seem to affect the enzyme activity. The second binding site binds 5 to 15 mol of oleate/mol of enzyme resulting in complete loss of the activity. This is followed by an increase in oleate binding to the third site of the enzyme. Sucrose density gradient centrifugation of oleate-inactivated enzyme indicated that the enzyme dissociated to the dimeric form. Similarly, centrifugation of [3H]oleate-treated enzyme revealed that all polymeric forms of phosphofructokinase bound approximately 6 to 8 mol of oleate/mol of enzyme. In the presence of fructose-6-P, oleate is bound to the polymers to a lesser degree and therefore protects against the fatty acid inactivation. Various polymers which are cross-linked with dimethylsuberimidate are also inhibited by oleate.

Adenosine Monophosphate↗

PubMed1992

Complexation of steroid hormones with cyclodextrin derivatives: substituent effects of the guest molecule on solubility and stability in aqueous solution.

The inclusion complexation of homologous derivatives of steroid hormones with cyclodextrins and 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) was investigated with regard to underlying structure-interaction relationship. The interaction was studied by phase solubility analysis and stabilization effects of complex formation with 2-HP-beta-CD. The solubilizing and stabilizing abilities of 2-HP-beta-CD were generally more effective for testosterone derivatives than for estradiol esters. Within a homologous series of steroid hormones, the steepest linear solubility isotherms were found for 17-methyl and 3-methyl derivatives. The solubilization of steroid esters by 2-HP-beta-CD depended on the structure and length of the ester side chain. The interaction of 2-HP-beta-CD with the steroids was hindered by long-chain fatty acid ester groups. With increasing length of the side chain, a decline of the isotherms occurred and the phase solubility behavior changed from linear to exponential. Contrary to expectations, benzoylation of steroids considerably decreased the guest-host interaction. The observed rates of degradation of the steroid esters were significantly reduced by 2-HP-beta-CD, depending on the chain length, and correlated well with the order found in phase solubility analysis. The degradation showed no deviations from pseudo-first-order kinetics, and the degradation mechanism was not changed because of complexation. The results suggest that interaction of 2-HP-beta-CD with steroid esters involves the ester functions of the prodrugs and is more suitable for unsubstituted guest molecules.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1992

Endothelial cell migration and chemotaxis in angiogenesis.

Our goal has been to provide a quantitative analysis of the random motility and chemotaxis of microvessel endothelial cells (MEC) in order to understand the role of these functions in the development of new capillaries. A major difference of our work from previous investigations has been our use of mathematical analysis to interpret experimental results, and to relate in vitro migration measurements to in vivo angiogenesis observations. In this paper we present some of our methods and their rationale, with recent results from both experiment and mathematical models.

Adipose Tissue↗

PubMed1992

N.m.r. study on the formation and geometry of inclusion complexes of 6-O-(alpha-maltosyl)cyclomalto-hexaose and -heptaose with p-nitrophenol in aqueous solution.

The formation and molecular geometry of inclusion complexes of some branched cyclomaltaoses with p-nitrophenol in aqueous solution have been investigated by using high-resolution 1H-n.m.r. spectroscopy. 6-O-(alpha-Maltosyl)cyclomalto-hexaose and -heptaose were found to form 1:1 inclusion complexes with p-nitrophenol, and the dissociation constants for their complexes are quite similar to those for corresponding unbranched cyclomaltaose-p-nitrophenol complexes, indicating that formation of these inclusion complexes is not hampered by the maltosyl branch. From measurement of nuclear Overhauser enhancements, it was concluded that the maltosyl branch is not situated over the entrance of the cavity.

Carbohydrate Sequence↗

PubMed1992

The influence of sucrose, dextran, and hydroxypropyl-beta-cyclodextrin as lyoprotectants for a freeze-dried mouse IgG2a monoclonal antibody (MN12).

The influence of lyophilization on the stability of a monoclonal antibody (MN12) was investigated. MN12 was freeze-dried in different formulations [without lyoprotectant or in the presence of sucrose, dextran, or hydroxypropyl-beta-cyclodextrin (HP beta CD)] and under varying conditions (with or without secondary drying). Subsequently, the monoclonal antibody was stored for 18 or 32 days at various temperatures (4, 37, or 56 degrees C). For comparison, solutions of MN12 were stored under the same conditions. Regardless of the lyoprotectant used, precipitation and a concomitant reduction of the antigen-binding capacity by about 10% were observed upon reconstitution of lyophilized MN12. HP beta CD proved to be the most effective stabilizer to prevent degradation of lyophilized MN12 during storage. Compared with MN12 solutions, HP beta CD-containing lyophilized MN12 cakes were more resistant to heat-induced charge alterations and loss of antigen-binding capacity.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1992

Inhibitory effect of 2-hydroxypropyl-beta-cyclodextrin on crystal-growth of nifedipine during storage: superior dissolution and oral bioavailability compared with polyvinylpyrrolidone K-30.

To prevent the crystal-growth of nifedipine during storage, 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was employed as a hydrophilic drug carrier and compared with polyvinylpyrrolidone K-30 (PVP). Amorphous nifedipine powders were prepared by spray-drying with HP-beta-CyD or PVP, and their crystal-growing behaviour at accelerated storage conditions were examined by X-ray diffraction analysis and microscopy. Although PVP initially retarded the crystallization of nifedipine, it failed to control the increase of crystal size after prolonged storage at 60 degrees C, 75% r.h., resulting in a remarkable decrease in dissolution rate in water. In sharp contrast, a relatively fine and uniform size of nifedipine crystals was maintained in the HP-beta-CyD system even after accelerated storage conditions. The enhanced dissolution observed for all the HP-beta-CyD systems in a dissolution medium containing 0.1% non-ionic surfactant HCO-60 were clearly reflected in the in-vivo absorption of nifedipine following oral administration to dogs. These results suggest that HP-beta-CyD is particularly useful in solving problems encountered on storage of amorphous nifedipine in solid dosage forms.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1992

Improved transdermal delivery of prostaglandin E1 through hairless mouse skin: combined use of carboxymethyl-ethyl-beta-cyclodextrin and penetration enhancers.

The optimal prescription of transdermal preparations of prostaglandin E1 (PGE1) for treatment of peripheral vascular diseases has been investigated. The chemical stability of PGE1 in fatty alcohol/propylene glycol (FAPG) ointment was markedly improved by carboxymethyl-ethyl-beta-cyclodextrin (CME-beta-CyD). Application of a PGE1 ointment containing the penetration enhancer, 1-dodecylazacycloheptane-2-one (Azone) or 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), onto the skin of hairless mice showed the increase of blood flow in the skin due to the vasodilating action of PGE1. In particular, the ointment containing a PGE1-CME-beta-CyD complex supplemented with HPE-101 showed the most prominent increase of the blood flow. Compared with other ointments, this ointment was found to show significantly greater transfer of HPE-101 into in-vitro preparations of the skin of hairless mice. Transfer of PGE1 into the skin was thought to be facilitated by this increased transfer of HPE-101. These results suggest that a combination of CME-beta-CyD and HPE-101 is useful for designing PGE1 ointments for topical application with good chemical stability and percutaneous permeability.

Administration, Cutaneous↗

PubMedDate not supplied

Preparation and physical evaluation of microcapsules of hydrophilic drug-cyclodextrin complexes.

An emulsion-solvent evaporation method for preparation of microcapsules containing water-soluble 2-hydroxypropyl-beta-cyclodextrin complex of a lipophilic water-insoluble drug, hydrocortisone, is described. The release of the drug from the microcapsules was determined in simulated gastric fluid. The drug release rate from the microcapsules could be controlled by addition of a plasticizer and it was sustained over extended time. Addition of solubilizing compounds to the dissolution medium did not affect the drug release rate.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1992

[Studies and preparations of fufang danshen granules].

With the preparation of borneol-beta-cyclodextrin inclusion compound, the stability of the product was improved. In the studies on quality standards, TLC method was used in the identification of three medicinal ingredients and TLC-ultraviolet spectrophotometry was used in the content determination of the chemical constituent tanshinone II A in Salvia miltiorrhiza.

Abietanes↗

PubMed1992

Use of 2-hydroxypropyl-beta-cyclodextrin as an intrathecal drug vehicle with opioids.

2-Hydroxypropyl-beta-cyclodextrin (CDEX), a seven-membered glucose pyranose structure, forms reversible inclusion complexes with the lipophilic portion of a drug molecule by noncovalent bonding. This can increase the water solubility of lipid-soluble drugs and reduce the rate of clearance of such agents from the spinal cord into the vasculature after i.t. administration. In this study, opioids (morphine, lofentanil, alfentanil and sufentanil) with and without CDEX (20, 2, 0.2 and 0.02% w/v in sterile water) were administered spinally in rats prepared with chronic i.t. catheters. CDEX prolonged the duration of analgesia (52.5 degrees C hot plate) and reduced the incidence of catalepsy otherwise produced by a supermaximal i.t. dose of each of the opioids. The magnitude of the potentiating effect of CDEX on opioids was dependent upon concentration of the CDEX and varied with drug lipid partition coefficients. The highest concentration of CDEX alone (20%) had no effect upon the volume-evoked micturition reflex, blood pressure, heart rate, or spinal reflexes. Our data indicate that CDEX may be a useful i.t. vehicle for modifying the redistribution characteristics of highly diffusible molecules after their i.t. administration, and that for each drug there is an optimal CDEX concentration. In the present case, CDEX prolongs the spinal analgesic action and reduces the supraspinal actions of i.t. drugs.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1992

Interactions between epidurally and intrathecally administered sufentanil and bupivacaine in hydroxypropyl-beta-cyclodextrin in the rat.

The interaction between inactive doses of the opioid sufentanil and the local anesthetic bupivacaine after complexation in various concentrations of hydroxypropyl-beta-cyclodextrin (HP-B-CD) were studied after epidural and intrathecal administration in the rat. Whereas 0.125 microgram sufentanil and 80 micrograms bupivacaine produced only limited effects, a combination of the two compounds resulted in a profound surgical analgesia in all rats tested after epidural administration. Also intrathecally, a clear potentiation was present. The complexation of the same doses of sufentanil plus bupivacaine in HP-B-CD increased the duration of analgesia. Epidurally, a maximal potentiation of analgesia was present at 0.125 microgram sufentanil plus 80 micrograms bupivacaine in 20% HP-B-CD. Intrathecally, maximal potentiation of the analgesic activity was present starting from a complexation of both drugs in 10% hydroxypropyl-beta-cyclodextrin. Higher concentrations of hydroxypropyl-beta-cyclodextrin did not significantly further increase the duration of analgesia. These results indicate that for both routes of spinal administration, the complexation of sufentanil plus bupivacaine in HP-B-CD can produce a longer analgesia than either plain sufentanil, sufentanil combined with bupivacaine or sufentanil alone in HP-B-CD. The complexation of sufentanil plus bupivacaine in HP-B-CD did not diminish the increased safety observed to occur after complexation of sufentanil in HP-B-CD and after combination of sufentanil plus bupivacaine.

2-Hydroxypropyl-beta-cyclodextrin↗