ULTRASOUND MECHANIC EFFECT APPLIED FOR INCREASING THE SOLUBILITY OF THE PURINIC ALKALOIDS

Transcription

1 ULTRASOUND MECHANIC EFFECT APPLIED FOR INCREASING THE SOLUBILITY OF THE PURINIC ALKALOIDS Alina-Elena ALUCULESEI Mihaela-Cristina ANTON V.S. GHERMAN Dana-Ortansa DOROHOI Al.I.Cuza University, Faculty of Physics, Iaşi Introduction In the propagation process, ultrasounds produce periodical movements of the component particles which are transmitted by the interactions between neighbouring particles, forming mechanic waves. The ultrasound waves are characterized by frequency, propagation seed and transported energy as well as by acceleration and speed of the particles which are in an oscillatory movement. The acceleration of the oscillations has great magnitude, therefore induces important forces able to produce substance dislocations and dispersion, broking of the chemical or quasi-chemical bonds at the biopolymer level as well as at the supramolecular or cellular level. In the propagation process, a part of the energy transported by the ultrasound can transform itself in mechanic labour of the friction forces, contributing at the heating of the environment and/or at the intensification of the disorganised thermal motion of the component particles in the propagation medium. Used in medical purposes, the ultrasounds require a good knowledge regarding the propagation process and their effects on the biological environment in order to avoid their destructive action on some tissues from the organism. The main effects of the ultrasounds propagating in condensed mediums are: the mechanic effect the ultrasound imprints to the particles oscillatory movements whose characteristics depend on the nature of the propagation medium, on frequency and the transported energy. the caloric effect the transformation of one part of the energy transported by the ultrasound into internal energy of the propagation medium the chemical effect the ultrasounds are able to provoke or catalyse chemical or biological reactions; they can change the biological structure of the biochemical components by polymerizations and depolymerization.

2 the optical effect ultrasounds can produce the cavitation phenomenon; involved in light signals emission. These signals have a very short duration and reduced intensity. the electrical effect the processes which accompany the ultrasound cavitations produce ionic crushes in the irradiated medium, accompanied by the apparition of some potential differences between distinct zones in the ultrasound field. the biological effect ultrasounds of small and moderate energy have a biopozitive effect because they ensure the increase in the reproduction rate of micro organisms. Material and methods The purinic alkaloids used in this study are: teobromine, caffeine, teofiline. Water, ethylic alcohol, clorophom have been used as solvents. The solution preparation and the method which we used: A certain quantity of teobromina, caffeine or teofiiline was homogenised with solvent for obtaining a solution with a precise concentration (standard solution). Solutions with decreasing concentrations were obtained by repeated dilutions of the initial solution. The ultrasounds used were characterized by a frequency of 1MHz and an emissive power of 10-3 W. Solutions was exposed to the ultrasound action for different intervals of time between 0 and 10 minutes. The solubility increasing as a result of ultrasound action has been controlled by a Carl Zeiss Jena spectrophotometer. The intensity of the absorption electronic bands in [ ] cm -1 spectral range has been measured. Fig. no. 1 The optical scheme of SPECORD UV-VIS spectrophotometer Carl Zeiss Jena; 1 and 2 UV and visible source; 3, 4, 6, 9, 8, 12, 15, 17, 16, 17 and 20 mirrors; 10 dispersive system in Littrow arrangement; 18 and 19 identical cells; 21 photomultiplicator Results and discussion The purinic alkaloids have a reduced solubility in water (1:1800 for teobromine; 1:180 teophiline; 1:150 caffeine and so on), ethylic alcohol

3 and chloroform. They are frequently used in treating different kinds of diseases, but they can not be administrated by injections because the optimal concentration necessary is not achieved in normal conditions. By their mechanical effect the ultrasound waves produce the fragmentation of the microcrystal of the purinic alkaloids, transforming them in isolated molecules. This effect is cumulative and irreversible. The solubility of purinic alkaloid in solutions of water, ethylic alcohol or chloroform is increased by ultrasound action, enssuring the optimal dozes necessary for the treatment. The spectral control on the solubility increasing has been made on the basis of Lambert-Beer law: I( x) = I(0) e εcx (1) In relation (1): I(x) the intensity of the radiation transmitted by the cell containing the analysed solutions; I (0) the intensity of the radiation transmitted by the cell containing the solvent; ε is molar coefficient of the extinction; x the width of the cell; c the concentration of the active spectrally substance in solution. From Lambert Beer law one can obtain the transmission factor: I( x) T = I(0) (2) and the absorptivity expressed in relation (3): ln 1 ln I(0) E = cx T = I ( x =ε ) (3) Some homogenous solutions with certain concentrations of purinic alkaloids were used for obtaining the calibration curve permitting the estimation of purinic alkaloids concentration in solutions exposed to ultrasound action (Fig 2). In the saturated solution of purinic alkaloids the concentration can not be controlled, the spectral measurements controlling only the increasing of the spectrally active substance concentration.

4 Fig. no. 2 The calibration curve for teobromine in ethanol with a lower concentration than in the saturated solution From fig. 3 it results that for different time intervals of the ultrasound action, the extinction is modified and increases with the increasing of the irradiation time. Fig. no. 3 The absorptivity of teobromine solution in ethanol for increasing interval of ultrasound action; C 1, t 1 =0; C 2, t 2 =1; C 3, t 3 =3; C 4, t 4 =5; C 5, t 5 =10 minutes The time intervals of ultrasound action varied between 0 and 10 minutes. The results obtained by measuring the electronic band absorptivity at different intervals of time in which the solutions were subdued to the action of ultrasounds are represented in Fig. 4. Fig. no. 4 The dependence of extinction measured in the maximum of the electronic absorption band versus the time of ultrasounds action on teobromine saturated solutions. The spectral absorptivity depends linearly on the duration of the ultrasound action. This permits us to appreciate if the Lambert-Beer law is applicable.

5 From Fig. 2 and 4 we observe that in the supersaturated solutions of teobromine the concentration is of about mol/l. The ultrasounds action for 10 minutes increases the concentration up to mol/l. This experiment shows that the saturated solutions subdued to the ultrasound action became more concentrated. Conclusion The spectral absorptivity of the solutions increases with the time interval of the ultrasound action. The aspects of absorption bands are not modified and this shows us that the substance does not change its chemical structure after interacting with ultrasounds. The salvation process is cumulative and irreversible. The increasing rate of the concentration of purinic alkaloids in solutions depends on their chemical nature. Bibliography 1. Manolescu, E., Farmacologie, Ediţia a II-a, Bucureşti, Editura Didactică şi Pedagogică, Goodman, L.S., Gilman, A., Bazele farmacologiei în tratament, Ediţia a II-a, Bucureşti, Editura Medicală, Diaconu, I., Dorohoi, D., Ultrasunetele. Aplicaţii în medicină, Iaşi, Editura Tehnopress, Profire, L., Costuleanu, M., Bumbu, G.G., Dănilă, Gh., Dorohoi, D., Vasile, C., 1 st International Pharmaceutical Congress, Aprilie, 2001, Atena, Grecia 5. Aluculesei, A., Gherman, V., Dorohoi, D., Controlul spectral al creşterii solubilităţii unor substanţe cu acţiune farmaceutică prin ultrasonare articol FTEM, Iaşi, mai, Aluculesei, A., Gherman, V., Profirie, E., Dorohoi, D., Spectral control on the methyl-xantines solubility increasing by ultrasound action. În: Conference National de Physic Applicant, Galaţi, July, 2005