Ejection liquid, ejection method, method of making droplets from liquid, cartridge and ejection device

Abstract

The present invention provides a liquid composition, as an ejection liquid used for stably ejecting liquid droplets, including at least one kind of a protein and a peptide, and a compound having a betaine skeleton by application of thermal energy to the liquid; a method of making droplets form the liquid; and an ejection method and an ejection device suitable for utilizing protein liquid droplets. By adding a compound having a betaine skeleton to an aqueous solution of at least one kind of a protein and a peptide, the liquid composition is improved in stability for ejection by application of thermal energy. Further, a surfactant may be further added to the liquid composition containing the compound having a betaine skeleton, and in this case the effect of stable ejection can be obtained.

Description

TECHNICAL FIELD[0001]The present invention relates to a liquid composition containing at least one kind of a protein and a peptide suitable for making droplets form the liquid composition, to a method of making droplets form the liquid composition, and to an ejection device using the method of making droplets form the liquid composition.BACKGROUND ART[0002]In these years, many attempts of using a protein solution as droplets have been made. Examples of such attempts include a transmucosal administration as a drug delivery method, and applications to a biochip or a biosensor because they need only a trace amount of protein. In addition, a method of using protein liquid microdroplets has also attracted attention in the field of screening a bioactive substance (Japanese Patent Application Laid-Open No. 2002-355025; Allain L R, et al., “Fresenius J. Anal. Chem.” 2001, Vol. 371, p. 146-150; and Howard E I, Cachau R E “Biotechniques” 2002, Vol. 33, p. 1302-1306).[0003]Recently, protein, p...

AI Technical Summary

Benefits of technology

[0024]According to the present invention, an ejection liquid which can be stably ejected after thermal energy has been applied thereto can be provided, by adding a compound having a betaine skeleton to a solution containing at least one kind of a protein and a peptide. In addition, it is further possible to eject a protein solution with a higher concentration by further adding a surfactant to the ejection liquid, because the addition provides a synergistic effect of stabilizing ejection. When at least one kind of a protein and a peptide is a pharmaceutically effective ingredient, at least one kind of the protein and peptide of the pharmaceutically effective ingredient arrives at a lung by ejecting the ejection liquid from a portable ejection device to convert it into liquid droplets, and inhaling the droplet, and the pharmaceutically effective ingredient can be absorbed by the lung. The above-described method can be also used for the preparation of a biochip or a biosensor, sensing, and screening for a biological substance, by ejecting at least one kind of the protein and peptide onto a substrate with the method.

Problems solved by technology

However, the inhaler has a problem that the size of a droplet in the above-described range is not sufficiently controlled, and besides, the pressure carrier may not be good for health.

Accordingly, it is theoretically possible for the atomising method to control a atomised amount by specifying a fluid volume of the liquid formulation supplied into such a capillary flow path, but is difficult to control the diameter of the droplet.

For this reason, it is structurally difficult to vary a quantity (density) of the microdroplets floating in airflow for transportation according to a purpose.

The liquid droplet formation of the above-described protein and peptide on the basis of a principle of the ink jet system has a problem that the protein has a frail spatial configuration and therefore may cause the aggregation and decomposition of the protein when the configuration has been destroyed.

They make the configuration of most of proteins unstable (When the thermal ink jet system is employed, heat is added thereto in addition to them).

The liquid droplet formation particularly on the basis of the principle of the ink jet system has the problem that storage in a long period is unstable, and further that the above-described physical force is extremely higher than the shear force and thermal energy applied in normal stirring and heat treatment.

For this reason, protein tends to become much more unstable than in a process of normally treating protein, so that there has been a case where a conventionally-used technology of stabilizing the protein is insufficient.

Once the problem happens, proteins aggregate while the droplets are formed, which causes clogging in a nozzle and makes the droplets hardly ejected.

Furthermore, a size of a droplet suitable for lung inhalation is 1 to 5 μm, which is very smaller than a droplet of about 16 μm used in a currently commercially available printer, and results in applying larger surface energy and shear force onto the droplet.

For this reason, it is extremely difficult to eject protein as microdroplets suitable for the lung inhalation.

However, the pamphlet does not describe the stability of ejection, furthermore, the addition of a surfactant and a water-soluble polymer shows the insufficient effect when the concentration of protein and peptide is high, and there was a case where an additive in itself aggravated the stability of the ejection.

In addition, many surfactants do not have an effect on the stability of the ejection at all, and in other words, surface tension, viscosity or a moisture retention effect does not control the stability of the ejection.

The oscillation type using the piezoelectric element has limitation in miniaturization for the piezoelectric element to be used, and accordingly in the number of installed ejection orifices per unit area.

In addition, a necessary cost for producing an ejection device sharply increases with the increase of the number of arranged ejection orifices per unit area.

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