Ravimipoliitika 2030

Eesti Arst 2023; 102(2):73–7

3D printimine farmaatsias – tee uudsete ravimkandursüsteemideni

Väitekirja elektrooniline versioon ei sisalda publikatsioonePersonaal- ehk täppismeditsiini abil soovitakse haiguseid ennetada, diagnoosida ja ravida viisil, mis saavutaks parima tulemuse konkreetsel patsiendigrupil. Mitmekülgsete teadmiste kasutamine sobivaima raviaine, annuse ja ravimvormi valimisel aitab kaasa oodatud ravitulemuse saavutamisele. Neid teadmisi aitab rakendada kolmemõõtmeline (3D) printimine. Tegu on meetodiga, kus arvuti abil disainitud mudel ehitatakse kiht kihi haaval soovitud objektiks. Sõltuvalt kihi lisamise viisist jaguneb 3D printimine erinevateks meetoditeks. Meetodi valik aga omakorda võib seada materjalide valikule lisatingimusi. 3D printimine sai alguse 1980ndatel ning on viimastel aastatel jõudnud ka meditsiinivaldkonda. Kirjandusest leiab põhjalikke ülevaateid selle kasutamisest nt kardioloogias, hambaravis, plastilises kirurgias, bioprintimisel. Ravimitööstuses nähakse 3D printimises võimalikku abimeest personaliseeritud ravimite tootmisel. Aastal 2015 sai müügiloa esimene 3D prinditud ravim Spritam®. Doktoritöös kasutati mikroekstrusioonil ning sulatatud sadestusega modelleerimisel põhinevaid printimistehnoloogiaid. Mõlema meetodi jaoks disainiti sobilik ravi- ja abiainete kombinatsioon. Sobivateks kandurpolümeerideks osutusid polüetüleenoksiid ja polükaprolaktoon, raviaineteks indometatsiin ja teofülliin. Sarnaselt klassikalisele ravimiarendusele vajab ka uudsete tehnoloogiate kasutuselevõtt põhjalikku eeltööd, et õppida tundma kasutatavate materjalide omadusi ning võimalikke protsessi ajal toimuvaid muutuseid. Seetõttu uuritigi doktoritöös nii materjalide printimiseelseid omadusi, näiteks viskoossus, füüsikalised omadused, sobivus filamentide tootmiseks jt kui ka saadud ravimkandursüsteemi printimisjärgseid omadusi nagu raviaine vabanemine, reageerimine kuumutamisele ja kiiritamisele. Lisaks töötati välja uudne meetod pooltahkete materjalide 3D-prinditavuse hindamiseks. Töö tulemused kinnitavad, et 3D printimine on farmaatsiateaduse jaoks paljulubav abimees tulevikuravimite arendamisel.Precision medicine is an approach to enhance the prevention, diagnosis, and treatment of diseases to benefit a specific group of patients. Using this knowledge to select the most suitable active pharmaceutical ingredients (APIs) and doses enables us to achieve the optimal therapeutic efficiency. Three-dimensional (3D) printing is an additive manufacturing technique that has been proposed as tool for the application of these principles. In 3D printing, previously designed model is then layer-by-layer formed into desired object. 3D printing methods differ from each other based on layer formation and can dictate additional material considerations. 3D printing has been studied since 1980s and has been widely used in medicine these previous years. In pharmaceutics, 3D printing can be seen as a possible aid for fabricating personalised drug delivery systems. In 2015 the first 3D printed medicine Spritam® was authorised. In this dissertation, micro-extrusion-based and fused deposition modelling 3D printing methods were used. Suitable active substance and excipient(s) formulations were designed for both methods. Polymers used were polyethylene oxide and polycaprolactone, active substances indomethacin and theophylline. As classical does development, so does the implementation of novel technologies need thorough knowledge of material and process characteristics. Therefore, bulk material properties such as viscosity, physical characteristics, suitability for filament extrusion etc, and final drug delivery system characteristics such as drug release, reaction to heat and radiation were studied. In addition, a novel method for evaluating the 3D printability was designed. We can conclude from the results of this work, that 3D printing promises great aid in developing novel drug delivery systems.https://www.ester.ee/record=b548577

Stand up paddle board and windsurf based activities in Estonia

Magistritöö Loodusturismi õppekavalVeekogud pakuvad hulgaliselt erinevaid võimalusi aeru- ja purjelauaga sõitmiseks. Surfamise võib liigitada nii spordi, rekreatiivse tegevuse kui ka turismi alla, olles samal ajal tugevalt seotud elustiiliga. Eestis on võimalik surfamisega tegeleda aastaringselt, kevadest sügiseni vee peal ja talisurfates jääl ning lumel. Töö eesmärgiks on kaardistada Eesti aeru- ja purjelauateenuse pakkujate ja harrastajate profiil, peamised sihtkohad ning teadlikkus veeohutusest ja mõjudest looduskeskkonnale. Autor viis läbi 10 intervjuud aeru- ja purjelauateenuse pakkujatega ning küsitluses osales 55 harrastajat. Aeru- ja purjelauasõitjad on iseõppijad ning instruktoreid koolitatakse üldjuhul surfiklubides kohapeal. Surfamine sobib igas vanuses inimestele ning suurimaks sõitma õppimise eelduseks on soov ennast sel alal arendada. Purjelauasõitjad on Eestis kogunenud rannikualadele, aerulauasõitjaid võib näha väga erinevatel veekogudel. Aeru- ja purjelauasõitjad ning teenusepakkujad on keskkonnateadlikud inimesed ning kuna nad veedavad palju aega looduses on vajalik keskkonnakaitselistes küsimustes ka nende arvamusi kuulda võtta. Veeohutuses on tähtsal kohal ilmastikuolude jälgimine ja ohutusvesti kandmine.Different water bodies offer a wide range of opportunities for stand up paddleboarding (SUP) and windsurfing. Surfing can be classified as sport, recreational activity or tourism, while being strongly connected to lifestyle. In Estonia, it is possible to surf all year round. From spring to autumn on the water and on ice and snow in winter. The purpose of this study was to map the profile of Estonian SUP and windsurfing service providers and participants, the main destinations and awareness of water safety and impacts on the natural environment. The author interviewed 10 SUP and windsurfing service providers and in form got 55 participants replies. SUP and windsurfing are self-taught and instructors are usually trained in on-site surf clubs. Surfing is suitable for people of all ages, and the will to learn is the most important quality. Windsurfers gather mostly in coastal areas of Estonia, but stand up paddleboarders can be seen on very different bodies of water. SUP and windsurfing service providers are environmentally conscious people, and as they spend a lot of time in the natural environment, it is necessary to hear their views on environmental issues. On water safety it is important to pay attention to weather contitions and to wear PFD

Seminariteenuste arendamine maamajutusettevõttes Lepiku Külalistemaja näitel

https://www.ester.ee/record=b5168339*es

Effects of life-long exercise on circulating free fatty acids and muscle triglyceride content in ageing rats.

Regular physical exercise has emerged, together with dietary restriction, as an effective intervention in delaying degenerative diseases and augmenting life span in rodents. The mechanisms involved remain largely unknown, although a beneficial influence on the age-related alteration of insulin sensitivity has been hypothesized. As muscle triglyceride (TG) accumulation is considered a reliable index of muscle insulin resistance, in this study we explored muscle TG content in 23-month-old male Sprague-Dawley rats subjected to life-long training. Plasma glucose. insulin. free fatty acid (FFA) and leptin levels were also measured. Both voluntary running in wheels (RW) and forced training in treadmill (TM) were studied. As RW rats weighed less than controls, a cohort of untrained animals, fed to pair weight (PW) with RW, was added to discriminate the effect of exercise from that of food restriction. Sedentary ad libitum fed rats served as controls. In 23-month-old RW rats. muscle TG content was reduced by 50% with respect to age-matched sedentary controls, while in TM group this reduction was smaller but still highly significant, and occurred independently on the changes in body fat mass. In both the trained rat groups, there was a significant decrease in circulating FFA levels and a trend to reduced insulin levels. In PW rats, muscle TG levels decreased similarly to RW rats, while plasma parameters were less modified. In particular, RW training was more effective than PW in preventing the age-related increase in circulating leptin levels. Our results suggest that voluntary exercise effectively counteracts the development of insulin resistance in the muscles of ageing rats as well as other related changes such as hyperlipacidaemia and compensatory hyperleptinaemia. Forced training or moderate food restriction appear slightly less effective than voluntary exercise in preventing age-dependent alterations in nutrient distribution and/or utilization. (C) 2004 Elsevier Inc. All rights reserved

3D-printability of aqueous poly(ethylene oxide) gels

Printing technologies combined with a computer-aided design (CAD) have found an increasing number of uses in pharmaceutical applications. In extrusion-based printing, the material is forced through a nozzle to form a three-dimensional (3D) structure pre-designed by CAD. The aim of this study was to evaluate the 3D-printability of biocompatible aqueous poly(ethylene oxide) (PEO) gels and to investigate the effects of three formulation parameters on the 3D printing process. The impact of PEO concentration (gel viscosity), printing head speed and printing plate temperature was investigated at three different levels using a full factorial experimental design. The aqueous PEO gels were printed with a bench-top extrusion-based 3D printing system at an ambient room temperature. The viscosity measurements confirmed that the aqueous PEO gels follow a shear-thinning behaviour suitable for extrusion-based printing. Heating the printing plate allowed the gel to dry faster resulting in more precise printing outcome. With the non-heated plate, the gel formed a dumbbell-shaped grid instead of straight lines. Higher concentration and more viscous PEO gels formed the best structured 3D-printed lattices. In conclusion, the accuracy and precision of extrusion-based 3D printing of aqueous PEO gels is highly dependent on the formulation (PEO concentration) and printing parameters (printing head speed, plate temperature). By optimizing these critical process parameters, PEO may be suitable for printing novel drug delivery systems.Peer reviewe

Effects of crosslinking on the physical solid-state and dissolution properties of 3D-printed theophylline tablets

Peer reviewe

Modeling of failure mode in knee ligaments depending on the strain rate

BACKGROUND: The failure mechanism of the knee ligament (bone-ligament-bone complex) at different strain rates is an important subject in the biomechanics of the knee. This study reviews and summarizes the literature describing ligament injury as a function of stain rate, which has been published during the last 30 years. METHODS: Three modes of injury are presented as a function of strain rate, and they are used to analyze the published cases. The number of avulsions is larger than that of ligament tearing in mode I. There is no significant difference between the number of avulsions and ligament tearing in mode II. Ligament tearing happens more frequently than avulsion in mode III. RESULTS: When the strain rate increases, the order of mode is mode I, II, III, I, and II. Analytical models of ligament behavior as a function of strain rate are also presented and used to provide an integrated framework for describing all of the failure regimes. In addition, this study showed the failure mechanisms with different specimens, ages, and strain rates. CONCLUSION: There have been several a numbers of studies of ligament failure under various conditions including widely varying strain rates. One issue in these studies is whether ligament failure occurs mid-ligament or at the bone attachment point, with assertions that this is a function of the strain rate. However, over the range of strain rates and other conditions reported, there has appeared to be discrepancies in the conclusions on the effect of strain rate. The analysis and model presented here provides a unifying assessment of the previous disparities, emphasizing the differential effect of strain rate on the relative strengths of the ligament and the attachment

Time-dependent mechanical behavior of human amnion: Macroscopic and microscopic characterization

Characterizing the mechanical response of the human amnion is essential to understand and to eventually prevent premature rupture of fetal membranes. In this study, a large set of macroscopic and microscopic mechanical tests have been carried out on fresh unfixed amnion to gain insight into the time-dependent material response and the underlying mechanisms. Creep and relaxation responses of amnion were characterized in macroscopic uniaxial tension, biaxial tension and inflation configurations. For the first time, these experiments were complemented by microstructural information from nonlinear laser scanning microscopy performed during in situ uniaxial relaxation tests. The amnion showed large tension reduction during relaxation and small inelastic strain accumulation in creep. The short-term relaxation response was related to a concomitant in-plane and out-of-plane contraction, and was dependent on the testing configuration. The microscopic investigation revealed a large volume reduction at the beginning, but no change of volume was measured long-term during relaxation. Tension–strain curves normalized with respect to the maximum strain were highly repeatable in all configurations and allowed the quantification of corresponding characteristic parameters. The present data indicate that dissipative behavior of human amnion is related to two mechanisms: (i) volume reduction due to water outflow (up to ∼20 s) and (ii) long-term dissipative behavior without macroscopic deformation and no systematic global reorientation of collagen fibers