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BETA CYCLODEXTRIN
β cyclodextrin = beta-Cyclodextrin = beta-CD
CAS Number:7585-39-9
EC Number:231-493-2
General description
β cyclodextrin is a cyclic oligosaccharide consisting of seven glucose subunits joined by α-(1,4) glycosidic bonds forming a truncated conical structure.
β cyclodextrin is widely used in food, pharmaceutical, cosmetics, and chemicals industries.
Application
β cyclodextrin is used as a complexing agent in drug delivery because it forms an inclusion complex with a drug molecule.
β cyclodextrin complex of cyclodextrin increases the aqueous solubility, dissolution rate and bioavailability of poorly water-soluble drugs, which is useful for the delivery of β cyclodextrin medical agent to a biological system.
Packaging
25, 100, 500 g in poly bottle
Molecular Formula: C42H70O35
Formula Weight: 1135.0
Possible impurities: Other cyclodextrins, linear oligomers
Solubility: (in 100 cm3 solvent, at 25 °C) : Water: < 2.0 g
Methanol: < 1.0 g
DMSO: > 10 g
CAS Number:7585-39-9
Molecular Weight:1134.98
Beilstein/REAXYS Number:78623
EC Number:231-493-2
MDL number:MFCD00078139
PubChem Substance ID:24892722
Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds.
Cyclodextrins are produced from starch by enzymatic conversion.
They are used in food, pharmaceutical, drug delivery, and chemical industries, as well as agriculture and environmental engineering.
Cyclodextrins are composed of 5 or more α-D-glucopyranoside units linked 1->4, as in amylose (a fragment of starch).
β cyclodextrin largest cyclodextrin contains 32 1,4-anhydroglucopyranoside units, while as a poorly characterized mixture, at least 150-membered cyclic oligosaccharides are also known.
Typical cyclodextrins contain a number of glucose monomers ranging from six to eight units in a ring, creating a cone shape:
α (alpha)-cyclodextrin: 6 glucose subunits
β (beta)-cyclodextrin: 7 glucose subunits
γ (gamma)-cyclodextrin: 8 glucose subunits
Synonym(s):
Schardinger β-Dextrin,
Cyclomaltoheptaose,
Cycloheptaamylose,
beta-Cyclodextrin,
Caraway
beta-CYCLODEXTRIN
Betadex
Cyclomaltoheptaose
Cycloheptaglucan
7585-39-9
Cycloheptaamylose
Cycloheptaglucosan
Kleptose
b-Cyclodextrin
beta-Cycloamylose
Cycloheptapentylose
Kleptose B
Rhodocap N
Ringdex B
Ringdex BL
beta-CD
beta-cyclodextrine
UNII-JV039JZZ3A
.beta.-Cyclodextrin
JV039JZZ3A
Caraway
CHEBI:495055
Schardinger beta-dextrin
NCGC00090771-01
DSSTox_CID_358
DSSTox_RID_75536
DSSTox_GSID_20358
beta-Cyclodextrins
CAS-7585-39-9
Dextrin, beta-cyclo
CCRIS 651
ss-Cyclodextrin
Cyclodextrin B
Beta cyclodextrin
Betadex [USAN:INN:BAN:NF]
Abbreviation: BCD
CAS Number: 7585-39-9
Product Number: 33
Cyclodextrin type: Native, neutral
Quality: pharma grade
Drug delivery
Cyclodextrins are ingredients in more than 30 different approved medicines.
With a hydrophobic interior and hydrophilic exterior, cyclodextrins form complexes with hydrophobic compounds.
Alpha-, beta-, and gamma-cyclodextrin are all generally recognized as safe by the U.S. FDA.
They have been applied for delivery of a variety of drugs, including hydrocortisone, prostaglandin, nitroglycerin, itraconazol, chloramphenicol.
β cyclodextrin cyclodextrin confers solubility and stability to these drugs.
The inclusion compounds of cyclodextrins with hydrophobic molecules are able to penetrate body tissues, these can be used to release biologically active compounds under specific conditions.
In most cases the mechanism of controlled degradation of such complexes is based on pH change of water solutions, leading to the loss of hydrogen or ionic bonds between the host and the guest molecules.
Alternative means for the disruption of the complexes take advantage of heating or action of enzymes able to cleave α-1,4 linkages between glucose monomers.
Cyclodextrins were also shown to enhance mucosal penetration of drugs.
Chromatography
β-cyclodextrins are used to produce stationary phase media for HPLC separations.
Other
Cyclodextrins bind fragrances. Such devices are capable of releasing fragrances during ironing or when heated by human body.
Such a device commonly used is a typical 'dryer sheet'.
The heat from a clothes dryer releases the fragrance into the clothing.
They are the main ingredient in Febreze which claims that the β-cyclodextrins "trap" odor causing compounds, thereby reducing the odor.
Cyclodextrins are also used to produce alcohol powder by encapsulating ethanol.
The powder produces an alcoholic beverage when mixed with water.
Structure
γ-CD toroid structure showing spatial arrangement.
Typical cyclodextrins are constituted by 6-8 glucopyranoside units.
These subunits are linked by 1,4 glycosidic bonds.
The cyclodextrins have toroidal shapes, with the larger and the smaller openings of the toroid exposing to the solvent secondary and primary hydroxyl groups respectively.
Because of this arrangement, the interior of the toroids is not hydrophobic, but considerably less hydrophilic than the aqueous environment and thus able to host other hydrophobic molecules.
In contrast, the exterior is sufficiently hydrophilic to impart cyclodextrins (or their complexes) water solubility.
They are not soluble in typical organic solvents.
Synthesis
Cyclodextrins are prepared by enzymatic treatment of starch.
Commonly cyclodextrin glycosyltransferase (CGTase) is employed along with α-amylase.
First starch is liquified either by heat treatment or using α-amylase, then CGTase is added for the enzymatic conversion.
CGTases produce mixtures of cyclodextrins, thus the product of the conversion results in a mixture of the three main types of cyclic molecules, in ratios that are strictly dependent on the enzyme used: each CGTase has its own characteristic α:β:γ synthesis ratio.
Purification of the three types of cyclodextrins takes advantage of the different water solubility of the molecules: β-CD which is poorly water-soluble (18.5 g/l or 16.3mM) (at 25C) can be easily retrieved through crystallization while the more soluble α- and γ-CDs (145 and 232 g/l respectively) are usually purified by means of expensive and time consuming chromatography techniques.
As an alternative a "complexing agent" can be added during the enzymatic conversion step: such agents (usually organic solvents like toluene, acetone or ethanol) form a complex with the desired cyclodextrin which subsequently precipitates.
β cyclodextrin complex formation drives the conversion of starch towards the synthesis of the precipitated cyclodextrin, thus enriching its content in the final mixture of products.
Wacker Chemie AG uses dedicated enzymes, that can produce alpha-, beta- or gamma-cyclodextrin specifically.
β cyclodextrin is very valuable especially for the food industry, as only alpha- and gamma-cyclodextrin can be consumed without a daily intake limit.
Crystal structure of a rotaxane with an α-cyclodextrin macrocycle.
Derivatives
Interest in cyclodextrins is enhanced because their host–guest behavior can be manipulated by chemical modification of the hydroxyl groups.
O-Methylation and acetylation are typical conversions.
Propylene oxide gives hydroxypropylated derivatives.
β cyclodextrin primary alcohols can be tosylated. The degree of derivatization is an adjustable, i.e. full methylation vs partial.
Both β cyclodextrin and methyl-β-cyclodextrin (MβCD) remove cholesterol from cultured cells.
β cyclodextrin methylated form MβCD was found to be more efficient than β cyclodextrin.
The water-soluble MβCD is known to form soluble inclusion complexes with cholesterol, thereby enhancing its solubility in aqueous solution.
MβCD is employed for the preparation of cholesterol-free products: the bulky and hydrophobic cholesterol molecule is easily lodged inside cyclodextrin rings.
MβCD is also employed in research to disrupt lipid rafts by removing cholesterol from membranes.
Research
In supramolecular chemistry, cyclodextrins are precursors to mechanically interlocked molecular architectures, such as rotaxanes and catenanes.
Illustrative, α-cyclodextrin form second-sphere coordination complex with tetrabromoaurate anion ([AuBr4]-).
Beta cyclodextrin complexes with certain carotenoid food colorants have been shown to intensify color, increase water solubility and improve light stability.
History
Space filling model of β cyclodextrin.
Cyclodextrins, as they are known today, were called "cellulosine" when first described by A. Villiers in 1891.
Soon after, F. Schardinger identified the three naturally occurring cyclodextrins -α, -β, and -γ.
These compounds were therefore referred to as "Schardinger sugars".
For 25 years, between 1911 and 1935, Pringsheim in Germany was the leading researcher in this area, demonstrating that cyclodextrins formed stable aqueous complexes with many other chemicals.
By the mid-1970s, each of the natural cyclodextrins had been structurally and chemically characterized and many more complexes had been studied.
Since the 1970s, extensive work has been conducted by Szejtli and others exploring encapsulation by cyclodextrins and their derivatives for industrial and pharmacologic applications.
Among the processes used for complexation, the kneading process seems to be one of the best.
Safety
Cyclodextrins are of wide interest in part because they are nontoxic.
The LD50 (oral, rats) is on the order of grams per kilogram.
Nevertheless, attempts to use β cyclodextrin for the prevention of atherosclerosis, age-related lipofuscin accumulation and obesity encounter an obstacle in the form of damage to the auditory nerve and nephrotoxic effect
β cyclodextrin (β-CD) is a cone-shaped molecule.
β cyclodextrin is hydrophilic at the outer surface of the cavity for many hydroxyl groups, but hydrophobic in the cavity.
So β-CD is soluble in water, and a variety of hydrophobic guest molecules can be encapsulated in its non-polar cavity.
Such a characteristic has been widely applied in the fields of drug-controlled release,32 separation33 and adsorption.
Lee et al.35 used formic acid as a catalyst to copolymerize N-methylol-acrylamide (NMA) and (β-CD) (CD-NMA).
The CD-NMA was grafted onto the cotton fibers by using CAN as an initiator.
It demonstrates that 40 °C is the optimum temperature, and above this temperature the graft yield decreases.
The optimum graft yield can be acquired from adjusting grafting time, reaction temperature, and CAN concentration.
CD-NMA grafted cellulose fibers can be used in the aroma finishing of cotton. The fragrance of CD-NMA grafted cellulose fibers treated with vanillin was retained even after prolonged storage, initially at room temperature for 7 days following at 80 °C for 7 days.
β cyclodextrin untreated cotton fibers retained the fragrance for less than 2 days.
poly(isopropyl acrylamide-co-maleic anhydride-β cyclodextrin), with pH and temperature sensitivity plus molecular inclusion function.
This novel hydrogel was obtained using free radical polymerization in aqueous solution.
A reactive β-CD-based monomer carrying vinyl carboxylic acid functional groups was synthesized via the reaction of β-CD with maleic anhydride (MAH) in N,N-dimethylformamide (DMF) at 80 °C.
The poly(NIPAAm-co-MAH-β-CD) was obtained by copolymerization of the monomer with NIPAAm.
Figure 8.25 shows the synthesis route.
β cyclodextrin equilibrium swelling ratio of the hydrogel was affected by pH and temperature.
β cyclodextrin can be seen that the equilibrium swelling ratio of hydrogel increased with the increase in pH.
At a certain pH, the equilibrium swelling ratio decreased with rising temperature; it descended drastically near the phase transition temperature.
he temperature/pH dual-sensitive hydrogel has a great potential application in the smart fabrics field.
If temperature/pH dual-sensitive hydrogel is grafted on to the fiber or fabric surface, the fabrics will become environmentally sensitive.
β cyclodextrin is anticipated that the fragrance molecules included in β-CD are capable of being released in a sustainable fashion by changing the temperature or pH.
Novel deodorant fabrics could be developed by loading the fragrance molecules into the β-CD.
PVA membranes containing β-cyclodextrin (CD) (PVA/CD membrane) were prepared and the permeation and separation characteristics for propanol isomers through the PVA/CD membranes were investigated by PV and EV.368 EV was more effective for the separation of propanol isomers through the PVA/CD membrane than PV.
The PVA/CD membrane preferentially permeated 1-propanol rather than 2-propanol from their
In particular, a mixture of 10 wt.% 1-propanol concentration was concentrated to about 45 wt.% through the PVA/CD membrane.
The permeation mechanism of propanol isomers through the PVA/CD membrane was discussed based on the solution–diffusion model.
MMMs were prepared by incorporating ZSM-5 zeolite particles into polydimethylsiloxane.
A uniform dispersion of the zeolite in the membrane was obtained.
β cyclodextrin membranes were characterized with SEM, and the effects of zeolite loading on membrane performance were evaluated.
β cyclodextrin was found that 80 wt.% ZSM-5 loading was optimal for selectivity.
Further increase in the zeolite loading either improved the selectivity slightly or even lowered the membrane selectivity while the membrane permeability was consistently reduced.
The improved separating performance of the filled membranes was attributed to the filler–polymer interactions, and the mass transfer contribution of surface flow through the zeolite pores.
The advantage of the improved membrane performance was demonstrated in a simulated continuous operation enriching 2,3-butanediol in a mixture with 1-butanol from 5 to 99.5 wt.% as a retentate using both the filled and unfilled PDMS membranes.
Results showed that the filled PDMS membrane improved the recovery of 2,3-butanediol significantly while achieving the same product purity.369
MMMs comprising polyamide–imide (PAI) and α-, β- or γ-cyclodextrin (CD) have been investigated experimentally and computationally for isomeric n-butanol/tert-butanol (n-BuOH/t-BuOH) separation via PV.
Consistent with molecular simulation, experimental results show that the CD inclusion ability and butanol discrimination ability are dependent on both CD cavity size and butanol molecular size.
β cyclodextrin PAI membrane incorporated with α-CD has the smallest cavity and has the highest discrimination ability for the n-BuOH/t-BuOH pair but with a low butanol flux.
β cyclodextrin MMM embedded with γ-CD has the lowest selectivity and the highest flux.
β cyclodextrin PAI/β-CD membrane has a comparable selectivity and flux and exhibits preferential sorption and diffusion selectivity toward n-BuOH.
A maximum separation factor of 1.53 with a corresponding flux of 4.4 g/(m2 h) are obtained at an optimal β-CD loading of 15 wt.%.
Further increments in the CD content eventually lead to a decrease in separation performance because of CD agglomeration and severe phase separation.
To better understand the influence of CD on the separation performance of MMMs, SEM, FTIR, and XRD have been employed for membrane characterizations.
The effect of n-butanol/t-butanol ratio in the feed composition has also been studied.
It is found that both flux and separation factor decrease with increasing n-butanol content in the feed.
The decline is attributed to the change in total vapor pressure at the upstream and the mutual drag effect of isomeric butanol molecules.370
A novel cyclodextrin (CD) derivative, m-xylenediamine-β-cyclodextrin (m-XDA-β-CD), has been synthesized and used to graft β-CD on membrane surface for the PV separation of butanol isomers.
The reaction mechanisms for the m-XDA-β-CD synthesis and the membrane surface grafting are confirmed by FTIR and TGA.
β cyclodextrin as-fabricated novel CD-grafted polyamide-imide (PAI) membranes show homogeneous morphology and significant improved separation performance as compared to the unmodified PAI membranes and PAI/CD MMMs made of physical blends.
β cyclodextrine effects of chemical modification time and dope concentration on the asymmetric membrane have been studied.
β cyclodextrin optimal separation performance can be found with the CD-grafted PAI membrane cast from a 22 wt.% dope concentration, which exhibits a total butanol flux of 15 g/(m2 h) and a separation factor of 2.03.
This newly developed membrane with surface-immobilized CD may open new perspective for the development of next-generation high-performance PV membranes for liquid separations.
Complex formation
β cyclodextrin, a cyclic oligosaccharide consisting of seven glucose units joined as α-(1 → 4) isomers, is nontoxic, edible, nonhygroscopic, chemically stable, and easily separable.
β cyclodextrin has a cavity at the center of the molecular arrangement and can thus form a stable insoluble inclusion complex with cholesterol.
The effectiveness of cholesterol adsorption is dependent on the adsorbent concentration, stirring time, speed, temperature, and centrifugation conditions.
Starch-containing products also seem to form stable complexes.
All of these complexes are stable in aqueous solutions, which allow removal of cholesterol from the lipid phase.
Incidentally, β cyclodextrin can be fermented by human colonic flora.
The safety aspect of residual β cyclodextrin from egg was studied in rats in a subchronic toxicity study and indicated no toxicity.
Extracted β cyclodextrin can be recovered by heating or by the addition of increasing amounts of sodium chloride, but the recovery of β-cyclodextrin from dairy products is ineffective since considerable amounts are needed for removal of cholesterol, which leads to high costs.
To overcome these problems, β cyclodextrin can be cross-linked with adipic acid or immobilized on a solid support.
A maximal level of β cyclodextrin of 5 mg kg-1 per day in foods is recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).
β cyclodextrin is ‘generally recognized as safe’ (GRAS) in the United States and a ‘natural product’ in Japan.
Cyclodextrins are a family of cyclic oligosaccharides with widespread usage in medicine, industry and basic sciences owing to their ability to solubilize and stabilize guest compounds. In medicine, cyclodextrins primarily act as a complexing vehicle and consequently serve as powerful drug delivery agents.
Recently, uncomplexed cyclodextrins have emerged as potent therapeutic compounds in their own right, based on their ability to sequester and mobilize cellular lipids. β cyclodextrin particular, 2-hydroxypropyl-β-cyclodextrin (HPβCD) has garnered attention because of its cholesterol chelating properties, which appear to treat a rare neurodegenerative disorder and to promote atherosclerosis regression related to stroke and heart disease.
Despite the potential health benefits, use of HPβCD has been linked to significant hearing loss in several species, including humans.
Evidence in mice supports a rapid onset of hearing loss that is dose-dependent.
Ototoxicity can occur following central or peripheral drug delivery, with either route resulting in the preferential loss of cochlear outer hair cells (OHCs) within hours of dosing.
Inner hair cells and spiral ganglion cells are spared at doses that cause ~85% OHC loss; additionally, no other major organ systems appear adversely affected.
Evidence from a first-to-human phase 1 clinical trial mirrors animal studies to a large extent, indicating rapid onset and involvement of OHCs.
All patients in the trial experienced some permanent hearing loss, although a temporary loss of function can be observed acutely following drug delivery.
The long-term impact of HPβCD use as a maintenance drug, and the mechanism(s) of ototoxicity, are unknown.
β-cyclodextrins preferentially target membrane cholesterol, but other lipid species and proteins may be directly or indirectly involved.
Moreover, as cholesterol is ubiquitous in cell membranes, it remains unclear why OHCs are preferentially susceptible to HPβCD.
β cyclodextrin is possible that HPβCD acts upon several targets—for example, ion channels, tight junctions (TJ), membrane integrity, and bioenergetics—that collectively increase the sensitivity of OHCs over other cell types.
β cyclodextrin is also possible to minimize the level of cholesterol in animal fat with an aqueous solution of bile salts and one or several glyceryl esters or with cyclic anhydrides such as succinic anhydride.
β cyclodextrin cholesterol-containing aqueous phase is then separated or the final product of the reaction with cyclic anhydrides is extracted with aqueous alkali.
In another method, animal fat is brought into contact with phospholipid or anionic polysaccharides.
β cyclodextrin formed sterol-reduced fat is then removed from the aqueous mixture.
Saponins such as quillaja powder (a commercial preparation of saponins from the bark of Quillaja saponaria), which are accepted for food processing and have received the GRAS list status in the United States, and also polymer-supported saponins such as digitonin (consisting of the aglycone digitogenin linked to a pentasaccharide) or tomatine (composed of a polycyclic steroidal secondary amine, tomatidine, and a tetrasaccharide) form insoluble cholesterol complexes, which can be removed by filtration or centrifugation.
The polymers may be regenerated by benzene extraction, which restores the original cholesterol-binding capacity.
Host–guest inclusion complexes of β-cyclodextrin with two vitamins viz., nicotinic acid and ascorbic acid in aqueous medium have been explored by reliable spectroscopic, physicochemical and calorimetric methods as stabilizer, carrier and regulatory releaser of the guest molecules.
Job’s plots have been drawn by UV-visible spectroscopy to confirm the 1:1 stoichiometry of the host-guest assembly.
Stereo-chemical nature of the inclusion complexes has been explained by 2D NMR spectroscopy.
Surface tension and conductivity studies further support the inclusion process.
Association constants for the vitamin-β-CD inclusion complexes have been calculated by UV-visible spectroscopy using both Benesi–Hildebrand method and non-linear programme, while the thermodynamic parameters have been estimated with the help of van’t Hoff equation.
Isothermal titration calorimetric studies have been performed to determine the stoichiometry, association constant and thermodynamic parameters with high accuracy.
β cyclodextrin outcomes reveal that there is a drop in ΔSo, which is overcome by higher negative value of ΔHo, making the overall inclusion process thermodynamically favorable.
β cyclodextrin association constant is found to be higher for ascorbic acid than that for nicotinic acid, which has been explained on the basis of their molecular structures.
Cyclodextrins (CDs) are the cyclic oligosaccharides containing six (α-CD), seven (β-CD) and eight (γ-CD) glucopyranose units, bound by α-(1–4) linkages forming a truncated conical structure.
Thus because of their unique structure, i.e., fairly rigid and well-defined hydrophobic cavities and hydrophilic rims having primary and secondary –OH groups (Fig. 1) they are of particular interest in the modern science.
CDs are used for controlled delivery of organic, inorganic, biological and pharmaceutical molecules due to their ability to form inclusion complexes with diverse guest molecules by encapsulating the non-polar part of the guest into its hydrophobic cavity and stabilizing the polar part by the polar rims.
β cyclodextrin use of CDs already has a long history in pharmaceuticals, pesticides, foodstuffs etc. for the solubility, bioavailability, safety, stability and as a carrier of the guest molecules.
CDs have been widely employed as not only excellent receptors for molecular recognition but also excellent building blocks to construct functional materials, where they could be applied to construct stimuli-responsive supramolecular materials.
Series of external stimuli, e.g., enzyme activation, light, temperature, changes in pH or redox and competitive binding may be employed to operate the release of guest molecules from the inclusion composites.
Recently cyclodextrin modified nanoparticles are of great interest as these supramolecular macrocycles significantly combines and enhances the characteristics of the entities, such as the electronic, conductance, thermal, fluorescence and catalytic properties expanding their potential applications as nanosensors, drug delivery vehicles and recycling extraction agents.
Different sophisticated probes based on semiconductor nanocrystals and other nanoparticles have been designed for this purpose, because of their potential applications in the fabrication of molecular switches, molecular machines, supramolecular polymers, chemosensors, transmembrane channels, molecule-based logic gates and other interesting host−guest systems.
In this article the studied two vitamins, e.g., nicotinic acid and ascorbic acid (Fig. 1) are the essential human nutrients with many important functions in biological systems.
Nicotinic acid is used to treat hypercholesterolemia and pellagra while its deficiency causes nausea, skin and mouth lesions, anemia, headaches, and tiredness.
On the other hand scurvy, fatigue, depression, and connective tissue defects are the common syndromes caused by deficiency of ascorbic acid.
Thus to protect these important bio-molecules from external effects (e.g., oxidation, structural modification etc.) and for their regulatory release, it is crucial to investigate whether these molecules can be encapsulated into the CD molecule and to explore the thermodynamic aspect of the process.
Guorong et al., Okazaki et al. and Delicado et al. showed different interactions of ascorbic acid with CD, while Manzanares et al., Silva et al., Pardave et al. and Hu et al. indicated the formation of inclusion complexes between ascorbic acid with β-CD by different electro and physicochemical methods.
On the other hand Terekhova et al. demonstrated nicotinic acid-CD interactions by volumetric and heat capacity studies.
In this present work the formation of host-guest inclusion complexes of these two vitamins with β-CD (the cavity dimension of which is more appropriate than other CDs to encapsulate a great variety of molecules) have been explored particularly towards their formation, stabilization, carrying and controlled release without chemical modification by different dependable methods like 2D ROESY NMR, UV-Vis spectroscopy, surface tension, conductivity and isothermal titration calorimetric studies, which primarily focuses on the encapsulation of the bio-molecules into the cavity of β-CD.
The stoichiometry, association constants and thermodynamic parameters for the inclusion complexes have been determined to communicate a quantitative data regarding the encapsulation of the vitamins by β-CD.
Cyclodextrins (CDs) are oligosaccharides used as complexing agents to increase the water solubility of lipophilic compounds and bio-availability of medicinal products.
Due to their cyclic structure, cyclodextrins can form inclusion complexes when they interact with hydrophobic drug substances; as a result, they demonstrate higher aqueous solubility than that of comparable acyclic saccharides.
cyclodextrins are made up of six, seven or eight dextrose units, forming α-, β-, and γ-Cyclodextrins respectively, with different cavity sizes.
Cavity size is the major determinant for the suitability cyclodextrins in complexations.
cyclodextrins have multiple applications. A great number of different pharmaceutical products containing cyclodextrins are currently on the market worldwide, mostly tablets, aqueous parenteral solutions, nasal sprays and eye drop solutions.
Examples of the use of cyclodextrins in medicines on the European market are β-CD in Cetirizine tablets and Cisapride suppositories, and γ-CD in Minoxidil solution.
SBE-β-CD has been designed to maximize safety and optimize interaction with drug molecules to improve the solubility, stability, bioavailability or lessen volatility, irritation, smell or taste of the drug.
For β-CD, which itself has a relatively low aqueous solubility, substitution of any of the hydrogen bond-forming hydroxyl groups, even by lipophilic functions, results in a dramatic improvement in the aqueous solubility of the SBE-β-CD derivative.
Cyclodextrins, and expecially beta ones, are widely used in the pharmaceutical field for their ability of improving the solubility and the stability of drugs by complex formation at the solid state.
Such phenomenon occurs only when cyclodextrin has a certain water content, being the removal of water from internal cavity essential for the interaction between the drug and the excipient.
Anyway, the dehydration of beta cyclodextrin leads to a product with peculiar properties, which is reported to be not able to form inclusion complex at the solid state, but is very effective in increasing the rate of complex formation in solution with a consequent strong influence on dissolution performances of drugs.
This approach is extremely interesting for obtaining fast dissolving tablets of drugs that are able for their own characteristics, to form stable solid inclusion complexes only in solution, but not at the solid state.
β cyclodextrin formulation process is extremely simple and of low cost involving only the physical mixing of the drug with the excipients before tableting or other pharmaceutical processes.
Cyclodextrins are cyclic oligosaccharides used for the improvement of water-solubility and bioavailability of drugs.
Because of the diverse types of application of cyclodextrins, several types of medicinal products may contain cyclodextrins.
β cyclodextrin are used for example in tablets, aqueous parenteral solutions, nasal sprays and eye drop solutions.
Examples of the use of cyclodextrins in medicines on the European market are β-CD in cetirizine tablets and cisapride suppositories, γ-CD in minoxidil solution, and examples of the use of β-cyclodextrin derivatives are SBE-β-CD in the intravenous antimycotic voriconazole, HP-β-CD in the antifungal itraconazole, intravenous and oral solutions, and RM-β-CD in a nasal spray for hormone replacement therapy by 17β-estradiol.
In Germany and Japan there are infusion products on the market, containing alprostadil (prostaglandin E1, PGE1) with α-CD.
Cyclodextrins are currently not included in the European Commission Guideline on excipients in the label and package leaflet of medicinal products for human use Both α-CD (Alphadex) and β-CD (Betadex) are listed in the European Pharmacopoeia (Ph.Eur.) and γCD is referenced in the Japanese Pharmaceutical Codex (JPC) and will be included in the Ph.Eur. A monograph for HP-β-CD (Hydroxypropyl-betadex) is available in the Ph.Eur.
In 2000-2004, α-CD, β-CD and γ-CD were introduced into the generally regarded as safe (GRAS) list of the FDA for use as a food additive.
Alpha- and beta-CD are approved as novel food ingredients by the Commission.
Beta-CD is approved in Europe as a food additive (E459) with an ADI (acceptable daily intake) of 5 mg/kg/day.
SBE-β-CD and HP-β-CD are cited in the FDA's list of Inactive Pharmaceutical Ingredients.
A novel approach for drug design based on the oral carbapenem analog tebipenem pivoxil (TP) has been proposed.
The formation of the tebipenem pivoxil-β-cyclodextrin (TP-β-CD) complex resulted in changes concerning physicochemical properties of TP, which is significant for planning the development of an innovative pharmaceutical formulation as well as in the modifications of biological activity profile of the studied delivery system.
The inclusion of TP into β-cyclodextrin (β-CD) was confirmed by spectral (infrared and Raman spectroscopies) and thermal method (differential scanning calorimetry). Precise indications of TP domains responsible for interaction with β-CD were possible through a theoretical approach.
The most important physicochemical modifications obtained as an effect of TP inclusion were changes in solubility and its rate depending on acceptor fluids, and an increase in chemical stability in the solid state.
Biologically essential effects of TP and β-CD interactions were decreased TP permeability through Caco–2 cell monolayers with the use of efflux effect inhibition and increased antibacterial activity.
β cyclodextrin proposed approach is an opportunity for development of the treatment in resistant bacterial infections, in which along with physicochemical modifications induced by a drug carrier impact, a carrier synergy with a pharmacological potential of an active pharmaceutical substance could be used.
β-Cyclodextrin is made of homogeneous cyclic α1,4-linked D-glucopyranose units in a seven member ring.
Forms clathrates and suitable for use with dansyl chloride to form water-soluble complexes for fluorescent labeling of proteins.
Beta cyclodextrin (βCD) is well-known as a potent drug carrier improving drug solubility, stability, and bioavailability.
The water layer adjacent to the membrane surface and lipophilic domain itself are a controlling barrier for drug transport.
However, the molecular details of the interaction between βCD and the lipid membrane has not yet been clearly explained.
Here, molecular dynamics simulations were performed to visualize the interaction process of the βCD molecule with the lipid bilayer for six microseconds in total.
Our results show that βCD passively diffuses into the lipid bilayer by pointing its open secondary rim toward the lipid polar groups and then remains at the phosphate and glycerol-ester groups with hydrogen bond formation.
The information obtained from this study may suggest that the association of βCD at the cellular membrane plays an important role for the transfer of drug and the extraction of cholesterol.
β cyclodextrin unsustainable nature of carbon-based fuels has prompted scientists and engineers to investigate alternative sources of energy.
Silver nanoparticle networks (AgNPNs) were synthesized using beta-cyclodextrin for applications in hydrogen evolution reactions from sodium borohydride (NaBH4).
The identities of the AgNPNs were confirmed using ultraviolet–visible spectroscopy, X-ray diffraction, and Transmission electron microscopy (TEM).
β cyclodextrin catalytic activity of the hydrogen evolution reactions was measured using a gravimetric water displacement system.
β cyclodextrin data collected show an increase in the efficiency of the hydrogen generation reaction with the addition of AgNPN.
β cyclodextrin silver nanoparticle network catalyst performed best at 22 °C with an increased concentration of NaBH4 producing hydrogen at a rate of 0.961 mL∙min−1∙mLcat−1. The activation energy was calculated to be 50.3 kJ/mol.
Introduction
β cyclodextrin carbapenems, which belong to the β-lactam antibiotics, are unique because of the broad spectrum of bacteriostatic activity due to the relative resistance to hydrolysis by most β-lactamases.
Therefore, carbapenems are antibiotics which nowadays, in the era of widespread antibiotic resistance, can be used as one of the very few options to treat severe hospital-acquired infections .
The greatest limitations of their application are:
(1) carbapenem resistance, mainly among Gram-negative pathogens, which involve active expulsion out of the periplasmic space after their entrance into bacteria,
(2) low bioavailability connected with hydrophilic properties, and
(3) significant degradation in the gastric environment in the solid state.
Due to the above-mentioned limitations, especially susceptibility to gastric environment, all carbapenem analogs, excluding tebipenem pivoxil (TP), must be administered parenterally.
TP is the first carbapenem analog recommended for oral administration as a prodrug.
TP shows activity against the majority of Gram-positive and Gram-negative bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes and Pseudomonas aeruginosa .
Esterification of the acidic group at C-2 bicycle 4:5 fused rings in tebipenem increases the lipophilicity of a molecule and also constitutes a priority location for acid catalyzed hydrolysis.
After the administration of tebipenem pivoxil, 54–75% of the dose is excreted in the urine as tebipenem.
Tebipenem pivoxil is considered to exhibit higher intestinal absorption than other β-lactam prodrugs (e.g. cefditoren pivoxil, cefcapene pivoxil, and cefetamet pivoxil).
The mechanism of drug permeability through biological barriers includes passive diffusion, active transport, paracellular and efflux pathways.
Knowledge about the absorption of β-lactam antibiotics provided information that their hydrophilic forms are absorbed through passive diffusion, while prodrugs also need peptide transporters.
Kato et al. suggested that tebipenem pivoxil is transported by OATP1A2 and OATP2B1 (organic anion transporting polypeptides) and not by MDR1 action (P-glycoprotein), as reported for other β-lactam prodrugs.
A significant chemical instability of carbapenems, including TP, has been confirmed by susceptibility to acid-base hydrolysis as well as thermolysis in the research concerning accelerated stability studies in the solid state.
β cyclodextrin was confirmed that the main degradation products of TP in the solid state were: a product resulting from the condensation of the substituents of 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinyl] sulphanyl, both acid and ester forms of tebipenem with an open β-lactam ring observed in dry air at an increased temperature (RH = 0%, T = 393 K), acid and ester forms of tebipenem with an open β-lactam ring observed at an increased relative air humidity and increased temperature (RH = 90%, T = 333 K).
During acid-base hydrolysis, tebipenem was also formed as the principal degradation product.
Although the chemical instability of tebipenem pivoxil is lower than reported for acidic forms of carbapenems, it is still a significant limitation of its use.
At the same time, the uncontrolled degradation of tebipenem pivoxil in the gastrointestinal tract promotes the formation of resistant strains related to the presence of its active form—tebipenem.
Moreover, in light of the proven catalytic effect of selected compounds (HCO3-) on the degradation of selected carbapenems (e.g. meropenem), it might appear that there are only a limited number of excipients which fulfill the criteria of valuable stabilizers of carbapenem analogs .
Carbapenem analogs stabilization with the simultaneous preservation of their antibacterial activity is of great importance considering current constraints in terms of severe bacterial infections and can constitute a precious solution for future therapies.
Considering that β cyclodextrin is necessary to stabilize carbapenem analogs and improve their permeability and antibacterial activity, cyclodextrins (CDs) may be recommended as auxiliary substances.
Cyclodextrins are biopolymers that contain six, seven or eight glucose monomers, linked by α-1,4-glucose bonds, referred to as α-, β- or γ-cyclodextrins, respectively. β cyclodextrin has been reported in a number of studies that CDs are able to form inclusion (host-guest) complexes with several antibiotics .
When used as complexing agents, CDs can also increase antibiotic’s solubility and enhance drug permeability through the membrane barrier, thus improving the bioavailability of the guest molecule, and modifying the antibacterial activity and chemical stability.
The effect of β-CD on aqueous solubility and dissolution rate was evaluated in the case of cefpodoxime proxetil .
β cyclodextrin was confirmed that the presence of β-CD effectively enhanced the aqueous solubility of cefpodoxime proxetil.
With regards to the influence of CDs on permeability, it was noted that hydroxypropyl β cyclodextrin and β cyclodextrin inclusion complexes significantly (p<0.01) increased the apparent intestinal permeability of trimethoprim by 39.8% and 56.1% respectively, when apparent permeability coefficients were determined using a Caco-2 permeability assay.
Antibacterial activity of cyclodextrin-included antibiotics was increased (especially for hydrophobic antibiotics), particularly against Gram-negative clinical strains.
β cyclodextrin was also reported that the formation of a meropenem β cyclodextrin inclusion complex increased meropenem chemical stability (during stability studies in the solid state at increased relative air humidity) of meropenem, which is important for the preparation and administration of its parenteral solutions.
Therefore, the aim of the present work was to prepare and characterize a tebipenem pivoxil inclusion complex with β cyclodextrin in order to achieve changes in the solubility, dissolution, chemical stability, Caco-2 permeability and antibacterial activity.
ß cyclodextrin is a cyclic heptamer composed of seven glucose units joined "head-to-tail" by alpha-1,4 links.
ß cyclodextrin is produced by the action of the enzyme, cyclodextrin glycosyl transferase (CGT), on hydrolyzed starch syrups.
CGT is obtained from Bacillus macerans, B. circulans or related strains of Bacillus.
As a result of its cyclic structure, ß-cyclodextrin has the ability to form inclusion compounds with a range of molecules, generally of molecular mass of less than 250.
β cyclodextrin may serve as a carrier and stabilizer of food flavours, food colours and some vitamins.
In take of ß-cyclodextrin from use as a food additive has been estimated at 1-1.4 g/day.
Other applications in decaffeination of coffee/tea and in reducing the cholesterol content of eggs by complexation followed by separation of the complex would make a much lower contribution to intakes.
Following a request from the European Commission, the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to re-evaluate the safety of β-cyclodextrin (E 459) when used as a food additive.
The Panel was not provided with a newly submitted dossier and based its evaluation on previous evaluations and reviews, additional literature that became available since then and the data available following a public call for data.
The Panel noted that not all original studies on which previous evaluations were based were available for the re-evaluation by the Panel.
β cyclodextrin (E 459) is authorised as a food additive in the European Union (EU) in accordance with Annex II and Annex III to Regulation (EC) No 1333/2008 on food additives and specific purity criteria have been defined in the Commission Regulation (EU) No 231/2012.
The Scientific Committee on Food (SCF) evaluated β-cyclodextrin (E 459) in 1996 and established an acceptable daily intake (ADI) of 0–5 mg/kg body weight (bw) per day based on a no observed adverse effect level (NOAEL) of 1.25% in the diet, equivalent to an intake of 466 mg/kg bw per day (based on urinalysis findings) in a 1-year dog study and applying an uncertainty factor of 100.
The Joint FAO/WHO Expert Committee on Food Additives (JECFA) evaluated β cyclodextrin (E 459) in 1993 and 1995 and in the latest evaluation established an ADI of 0–5 mg/kg bw per day from the 1-year study in dogs.
In animals and humans, β cyclodextrin (E 459) is hydrolysed by the gut microflora and endogenous amylases in the colon to maltose and glucose, which can be absorbed. Therefore, concentrations of β-cyclodextrin in tissues and serum are low (< 1%).
Urinary excretion varies with species but is in most cases less than 5% of the oral dose.
Introduction
Oral bioavailability of poorly aqueous soluble drugs remains one of the most challenging aspects for researchers in formulation development of dosage forms.
Nearby, 70 % of existing new drug molecules are poorly aqueous soluble and require a suitable candidate for enhancing oral bioavailability and solubility.
Drugs having the water solubility of <10 mg/ml over the pH range of 1-7 at 37°C show bioavailability issues.
According to Biopharmaceutical Classification System (BCS), drugs which are poorly soluble but highly permeable falls under BCS class II category.
These poorly aqueous soluble drug molecules exhibit slow drug absorption leading to poor and erratic bioavailability and finally causes GI mucosal toxicity.
Low solubility, poor dissolution rate and compromised oral absorption are the major problems of BCS Class II drugs and hence enhancing solubility of such actives is a major challenge for the pharmaceutical and academic researchers.
Cyclodextrins (CDs) represents one of the pharmaceutical excipient in overcoming this challenge.
CDs are molecules of natural origin, discovered earlier by Villiers in 1891.
The interest in application of CDs was later on studied by Austrian microbiologist Franz Schardinger in the twentieth century which became the most important topic of interest in pharmaceutical and other fields since from late 1970s to later on.
He described about two crystalline compounds isolated from bacterial digest of potato starch called α-dextrin and β-dextrin which were later and now called as α-CD and β-CD.
Over the span of time, CDs have created a quality platform for various applications like increasing drug solubility and stability, masking odors and tastes, enhancing drug absorption, controlling drug release profiles, alleviating local and systemic toxicity, and improving drug permeability across biological barriers.
CDs containing formulations have been delivered through various delivery systems like oral, ocular, nasal, dermal and rectal.
From application point of view, CDs offers various advantages like non-toxic, low cost, safety (recognized by safety health authorities) and easily available. Various published reports demonstrate wide application of CDs to enhance oral bioavailability of poorly aqueous soluble drugs.
Structure of CDs
CDs are cyclic oligosaccharides obtained from starch degradation by cycloglycosyl transferase amylases produced by various bacilli (Bacillus macerans and B circulans). Depending on the exact reaction conditions, three main types of CDs are obtained, α-, β-, and γ-CD, each comprises six to eight dextrose units respectively.
CDs are ring molecules which lack free rotation at the level of bonds between glucopyranose units, they are not cylindrical rather they are toroidal or cone shaped.
CDs consists of hollow tapered cavity consist of 0.79 nm in depth in which the active molecule is incorporated.
The primary hydroxyl groups are located on the narrow side whereas the secondary groups are on the wider side.
The properties of CDs can be modified by substituting different functional groups on the CDs rim.
Substituting the hydroxyl group of CD by chemical and enzymatic reactions by variety of substituting groups like hydroxypropyl-, methyl-, carboxyalkyl-, thio-, tosyl-, amino-, maltosyl-, glucosyl-, and sulfobutyl ether-groups to β-CD can increase the solubility.
Solubility of nonpolar solutes occurs due to the nonpolar nature (lipophilic) of the internal cavity of CDs whereas, the polar nature (hydrophilic) of CDs external part helps in solubilising the CDs and drug in aqueous solution.
Due to this characteristics nature, CDs have attained a great interest as a solubilising candidate and has overcome the biopharmaceutical deficiencies of various drugs in the recent years.
CDs are widely soluble in some polar, aprotic solvents, but insoluble in most organic solvents.
Although, CDs exhibit higher solubility in some of the organic solvents than in water, inclusion complexes do not take place in non-aqueous solvents because of the increased affinity of guest molecule for the solvent compared to its affinity for water.
Strong acids such as hydrochloric acid and sulfuric acid can hydrolyze CDs.
This hydrolysis rate depends upon temperature and concentration of the acid.
CDs are stable against bases.
β cyclodextrin hydrophobic cavity in CDs can partially accommodate low molecular lipophilic drug molecule and polymers.
Hydrophilic drug-CD complexes are formed by inclusion of lipophilic drug or lipophilic drug molecule in the central cavity.
β cyclodextrin lipophilic cavity thus protects the lipophilic guest molecule from aqueous environment, while the outer polar surface of the CD provides the solubilizing effect.
β cyclodextrin (β-CD) is a compound of great application for pharmaceutical and food industries, and is generally produced by starchy substrates by cyclomaltodextrin glucanotransferase (CGTase) action.
The objective of this study was to produce β-CD using an alternative source of starch, such as jackfruit seed (Artocarpus intergrifolia L.) bran (JSB) by a commercial CGTase.
The highest productivity of β-CD (52.10 µM/h.g) was obtained from 10 g of JSB in 100 mL of citrate buffer (10 mM / pH 6.0), with 17 % (v/v) of ethanol and 1.34 U/g of CGTase, at 59 °C for 4 hours.
These same conditions were applied to starches extracted from the JSB (SJSB) and ginger (SG) and also, potato starch (SP).
The SJSB and SG performances were similar to SP, and resulted in productivities around 2.7 times higher in relation to JSB.
Thus, it is possible to conclude that both JSB and SJSB are promising substrates for β-CD production.
Background. The research results of fat-soluble vitamin D3 (cholecalciferol) encapsulation with β cyclodextrin have been presented in this work.
β cyclodextrin vitamin D3 inclusion complex with β cyclodextrin was obtained under microwave radiation.
β cyclodextrin surface morphology of obtained clathrate inclusion complexes was described with the help of a scanning electron microscope.
β cyclodextrin thermographic measurement results on a differential scanning calorimeter have been presented.
β cyclodextrin activation energy of the β cyclodextrin : vitamin D3 clathrate complex thermal oxidative destruction reaction was calculated.
β cyclodextrin clathrate thermal destruction kinetic parameters were determined.
β cyclodextrin inclusion complex spectral properties were characterized by IR-Fourier and 1H and 13C NMR spectroscopy.
β cyclodextrin existence of β cyclodextrin inclusion complex with vitamin D3 in a 2 : 1 ratio was confirmed by the experimental results.
β cyclodextrin activation energy of thermal destruction of the inclusion complex of β-cyclodextrin with vitamin D3 was calculated using four different methods.
Herein, a novel biocompatible and stimuli-responsive network gel has been developed by grafting and crosslinking poly(N-isopropyl acrylamide) and poly(methacrylic acid) on cyclic oligosaccharide β cyclodextrin [β-CD-cl-(PNIPAm-co-PMAc)].
Various characterizations (such as NMR spectroscopy, CHN analysis, LCST measurement, and FESEM analysis) have been performed to confirm the formation of copolymer.
Swelling characteristics reveal that the developed hydrogel demonstrates dual responsive behaviour (pH and thermo-responsive).
β cyclodextrin copolymer shows viscoelastic properties and is characterized with excellent yield stress as well as compressive stress.
β cyclodextrin network hydrogel displays a non-cytotoxic nature towards MG-63 cell lines.
β cyclodextrin simultaneous in vitro release of metronidazole and ofloxacin from the gel endorses that it released both the colonic drugs simultaneously at the preferred pH (colonic pH 7.4) and body temperature (37 °C) at a desired rate.
Finally, the β-CD-cl-(PNIPAm-co-PMAc) gel is probable to be promising for targeted and sustained release of metronidazole and ofloxacin as is obvious from in vivo analysis.
Niemann-Pick type C disease (NPC) is a lysosomal storage disorder causing accumulation of unesterified cholesterol in lysosomal storage organelles.
Recent studies have shown that hydroxypropyl β cyclodextrin injections in npc1−/− mice are partially effective in treating this disease.
Using cultured fibroblasts, we have investigated the cellular mechanisms responsible for reduction of cholesterol accumulation.
We show that decreased levels of cholesterol accumulation are maintained for several days after removal of cyclodextrin from the culture medium.
This suggests that endocytosed cyclodextrin can reduce the cholesterol storage by acting from inside endocytic organelles rather than by removing cholesterol from the plasma membrane.
To test this further, we incubated both NPC1 and NPC2 mutant cells with cholesterol-loaded cyclodextrin for 1 h, followed by chase in serum-containing medium.
Although the cholesterol content of the treated cells increased after the 1-h incubation, the cholesterol levels in the storage organelles were later reduced significantly.
β cyclodextrin covalently coupled cyclodextrin to fluorescent dextran polymers.
These cyclodextrin–dextran conjugates were delivered to cholesterol-enriched lysosomal storage organelles and were effective at reducing the cholesterol accumulation.
β cyclodextrin demonstrate that methyl β cyclodextrin is more potent than hydroxypropyl-β cyclodextrin in reducing both cholesterol and bis(monoacylglycerol) phosphate accumulation in NPC mutant fibroblasts.
Brief treatment of cells with cyclodextrins causes an increase in cholesterol esterification by acyl CoA:cholesterol acyl transferase, indicating increased cholesterol delivery to the endoplasmic reticulum.
These findings suggest that cyclodextrin-mediated enhanced cholesterol transport from the endocytic system can reduce cholesterol accumulation in cells with defects in either NPC1 or NPC2.
Cyclodextrins are commonly used as a safe excipient to enhance the solubility and bioavailability of hydrophobic pharmaceutical agents.
Their efficacies and mechanisms as drug-delivery systems have been investigated for decades, but their immunological properties have not been examined.
β cyclodextrin this study, we reprofiled hydroxypropyl β cyclodextrin (HP-β-CD) as a vaccine adjuvant and found that it acts as a potent and unique adjuvant.
HP-β-CD triggered the innate immune response at the injection site, was trapped by MARCO+ macrophages, increased Ag uptake by dendritic cells, and facilitated the generation of T follicular helper cells in the draining lymph nodes.
β cyclodextrin significantly enhanced Ag-specific The and IgG Ab responses as potently as did the conventional adjuvant, aluminum salt (alum), whereas its ability to induce Ag-specific IgE was less than that of alum.
At the injection site, HP-β-CD induced the temporary release of host dsDNA, a damage-associated molecular pattern.
DNase-treated mice, MyD88-deficient mice, and TBK1-deficient mice showed significantly reduced Ab responses after immunization with this adjuvant.
Finally, we demonstrated that HP-β-CD–adjuvanted influenza hemagglutinin split vaccine protected against a lethal challenge with a clinically isolated pandemic H1N1 influenza virus, and the adjuvant effect of HP-β-CD was demonstrated in cynomolgus macaques.
Our results suggest that HP-β-CD acts as a potent MyD88- and TBK1-dependent T follicular helper cell adjuvant and is readily applicable to various vaccines.
Is Beta-cyclodextrin a Veterinary Medicine/Drug?
β cyclodextrin is a point when a carbohydrate is also a drug.
β cyclodextrin is when its use is put to a medical purpose in its own right, with verifiable facts to support its activity.
The definitions vary to some extent: ‘Therapeutic agent; any substance, other than food, used in the prevention, diagnosis, alleviation, treatment, or cure of disease.
And from the Oxford Dictionary; ‘Medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body.
Beta cyclodextrin is a carbohydrate which essentially is not digested by mammalian digestive enzymes.
Nor is it absorbed.
Beta-cyclodextrin as a therapeutic agent acts within the intestinal tract to provide a treatment for cryptosporidiosis (in calves).
As KRYPTADE and EXAGEN are marketed with therapeutic claims it is not classed as nutraceutical, but as a medicine.
β cyclodextrin medical claim is not related to its prebiotic function, which is a nutraceutical feature of the compound.
In the New Zealand veterinary market any medical claims made, need to meet a scientific standard of performance.
How does beta cyclodextrin work as an anti cryptosporidial active ingredient?
There are at least three hypothetical methods by which beta-cyclodextrin is thought to support oocystocidal activity and reduce oocyst output.
More research is needed to prove and define these but studies do show a direct link between beta cyclodextrin and loss on oocyst infectivity as described below.
What is interesting, is its effects could be having a wide variety of different actions; from direct effects on the oocyst, to reducing a cofactor of excystment, and also interference with attachment it self.
One key feature of beta-cyclodextrin is not only its insolubility in water but rather its very strong tendency to dissolve in cholesterol.
β cyclodextrin is over 1000 more soluble in cholesterol than water.
Direct Effect on Oocysts:
β cyclodextrin the more scientific supported studies, where there is direct contact between beta cyclodextrin and oocysts, there is evidence of rapid loss of infectivity on oocysts (Castro-Hermida et al).
These studies also show a direct effect of alpha-cyclodextrin on oocyst survival.
Indirect Effects on Ex-cystment:
There is also indirect evidence of interaction between bile-salts and beta-cyclodextrin; bile salts are cofactors that aid the excystment of oocysts.
Bile salts have similar characteristics to cholesterol, which have cholesterol as its base.
In theory at least β cyclodextrin is possible beta cyclodextrin could be interfering with the excystment process, reducing the overall infectivity of oocysts.
Host‐guest inclusion complex (IC) of vitamin C with β cyclodextrin (β‐CD) in aqueous medium has been explored by spectroscopic, physicochemical and calorimetric methods as stabilizer, carrier and regulatory releaser.
Job plot has been drawn by UV‐visible spectroscopy to confirm the 1:1 stoichiometry of the host‐guest assembly.
Stereo‐chemical nature of the inclusion complex has been explained by two‐dimensional (2D) NMR spectroscopy.
Surface tension and conductivity studies
