1) Patent granted: Production of highly bioavailable iron encapsulating nano-liposomal vectors with continuous technique.

Since 2018 Eng4Life owns the patent “Process for preparing nanoliposomes comprising micronutrients and food products comprising said nanoliposomes”. The invention process object of the patent (n ° 102017000099627) realizes a contact between two flows, on the one hand the phospholipids, preferably consisting of phosphatidylcholine and cholesterol, in an alcoholic solution, and on the other, according to the invention, an aqueous solution containing iron (Fe (II)).

The contact takes place inside a tubular device in which interdiffusion phenomena between the two phases cause the formation of nanometric lipid vesicles, containing the salt of Fe (II) in association with the reducing compound. The invention aims to overcome the limitations of the most used techniques for the production of liposomes. These techniques require long times and high energies, high costs of microfabrication of the implant devices and low productivity. In order to overcome these limitations, the innovation object of the patent application has transposed the microfluidic techniques, of recent literature, to a millimeter scale, called microfluidic-like, an intermediate scale between the microfluidic and macrofluidic ones.

In particular, the invention consists in the design and development of a simple device suitable for a massive production of nanoliposomes, which allows to overcome the limits imposed by the previous devices. The equipment and devices that can be used for a microfluidic-like process are more common and less expensive than those needed for microfluidics, and the production flow rates involved in microfluidics are higher than those of microfluidics, allowing to work with a high control of the operating conditions consequent to the laminar motion regime.

The patent can be consulted at the following link.

 2) Patent granted: Continuous process for the coating of liposomal vectors Since 2019 Eng4Life owns the patent “Continuous process for coating liposomial vectors with polymer”.

The invention object of the patent (No. 102018000002631) concerns a process for the polymer coating of liposomal nano-carriers with a continuous, and therefore rapid, high-productivity technique. Through this process we aim to obtain nanoliposomes perfectly coated with chitosan, a natural biocompatible polymer designed to increase the stability of the nanostructures and the mucoadhesiveness.

The invention makes use of the “microfluidic-like” technique, conceived by the spin-off object of a previous patent application, with high productivity for the formation of nanoliposomes, coupled with ultrasounds for the homogenization of the nanoliposomes obtained. The production method allows to obtain nanoliposomes with an average size lower than or equal to 100nm and characterized by a low polydispersivity index. In the invention, a new method of polymeric coating of liposomes was devised which uses a similar microfluidic device for the massive production of polymer-lipid particles, consisting of liposomes uniformly coated with chitosan.

The technique proposed according to the invention is based on the contact between two streams: a suspension of nanoliposms, previously produced, and a chitosan solution, respectively fed by two volumetric pumps. It has been found that in these conditions the meeting between two phases, one consisting of nanoliposomes in hydroalcoholic suspension and the other consisting of an acidulous aqueous solution containing chitosan, produces nanometric-sized structures uniformly coated with polymer.

The flow rates and dimensions of the selected pipes play a key role in the production of stable and perfectly polymer coated liposomal systems, and ensure that the fluids always flow in a laminar flow regime. These fluid-handling conditions allow a continuous and uniform interaction between equal volumes of liposomes and chitosan, overcoming the limitations of discontinuous techniques. With the proposed invention, nanostructures covered with chitosan are obtained, of medium size and with a low polydispersivity index, therefore homogeneous in size.

The patent can be consulted at the following link.

3) Patent pending: Method and device for determining the alcohol content of aqueous solutions using gas sensors

In order to overcome the limitations of the prior art, according to a first aspect of the invention, a method has been developed capable of providing a rapid and precise evaluation of the ethanol content of hydroalcoholic solutions, including commercial beverages, by measuring the alcohol concentration in a corresponding vapor phase.

According to another aspect of the invention, the proposed method has been reproduced in practice thanks to a specially designed device, suitable to be used for the determination of the alcohol content of solutions and beverages of any strength. In the method of the invention, the solution to be analyzed is first diluted with water in the liquid phase, so as to minimize the partial pressure of the volatile organic compounds in the corresponding vapor phase.

The resulting vapor phase can then be aspirated by means of a device, such as a vacuum pump, and sent to a device capable of mixing this stream with air, such as a venturi injector. The alcohol-enriched air mixture can thus be sent to gas sensors for ethanol analysis, such as semiconductor sensors, to then be discharged into the environment. The dilution of the vapor phase with air has the advantages of bringing the alcohol content back into the measurement range of commercially available gas sensors and limiting the influence of the humidity of the current to be analyzed on the sensor response. By alternating loading phases, in which the air stream is mixed with alcohol vapors, and cleaning phases, in which the air stream is sent pure, and possibly heated, to the sensors, it is possible to alternate measurement stages with regeneration stages. sensors, if needed. Through the use of a calculation module equipped with analog and / or digital pins for output and input communications, such as a single board microcontroller and appropriate circuitry, it is possible to modulate the inlet air flow and the mixing ratio, and analyze the response of the sensors so as to be able to quantify the concentration of alcohol present in the gaseous phase.

The sensor response can be correlated to the alcohol concentration in the gas phase through calibration curves constructed from the analysis of solutions whose liquid phase has a known alcoholic concentration and whose concentration of ethanol in the vapor phase has been obtained by means of thermodynamic models and / or by means of known semi-empirical models. Therefore, for the analysis of a sample of unknown title, the sensor response is linked to the concentration in the gas phase, and then, by means of thermodynamic and / or semi-empirical models already mentioned, it is possible to calculate the unknown ethanol concentration in the liquid phase. In this way, the effect of volatile organic compounds is canceled, the effect of temperature is taken into account (through pure thermodynamic calculation or through the use of semi-empirical equations) and avoids having to dehumidify the current sent to the sensors.

4) Patent pending: Method and device for the simulation of gastric ph histories for dissolution and release tests of pharmaceutical formulations in vitro

In order to improve conventional drug release and dissolution tests, according to the present invention, a method and a device capable of simulating, faithfully reproducing them, the pH variations that occur over time in the gastric environment have been developed. represented by a buffer solution, used to test pharmaceutical dosage units for oral use. The proposed method makes use of the use of two simple solutions (acid and base), compatible with the rules of the pharmacopoeia, and the use of a stand-alone device capable of controlling the pH of the solution in feedback. Specifically, in the proposed method the dissolution medium is represented by the common saline solutions suggested by the various pharmacopoeias, such as PBS – Phospate Buffer Saline.

Thanks to the dosage of two solutions, one acidic and one basic, and by means of a feedback control based on the pH value measured by a probe, it is possible to simulate in vitro pH histories similar to those recorded in vivo, both with decreasing pH and increasing, thus being able to obtain release data of active ingredients more similar to the real ones. The device takes from two different tanks, through pumps, for example peristaltic, a basic or acid solution which have the purpose of correcting the pH following a reference value (set point) that varies over time. Non-limiting examples of such solutions can be distilled water and sodium hydroxide, and distilled water and hydrochloric acid.

The device takes from two different tanks, through pumps, for example peristaltic, a basic or acid solution which have the purpose of correcting the pH following a reference value (set point) that varies over time. Non-limiting examples of such solutions can be distilled water and sodium hydroxide, and distilled water and hydrochloric acid. The proposed device, in addition to the verification and feedback control of the pH of the aforementioned solution, allows accurate monitoring, instant by instant, of the volumes involved, thanks to an innovative system for determining the flow rate of the dosing pumps (for example peristaltic) which allows you to avoid adding flow meters to the device. In light of the current limitations of in vitro tests, the present invention therefore confers greater veracity to said tests, guaranteeing the simulation of pH histories comparable to those that are carried out in vivo.