Patent Grant
8985100
The present invention relates to an inhalation therapy device for use in premature babies and infants.
Premature babies of less than 34 weeks gestation suffer from a surfactant deficiency syndrome. Synonyms for this disease are: HMD (Hyaline Membrane Disease), respiratory distress syndrome in premature babies, IRDS (Infant Respiratory Distress Syndrome). Surfactant replacement therapy is already well established and belongs to the standard methods of therapy in neonatology (the branch of medicine concerned with premature babies and newborns). In order to indicate the scale of the field of use of an inhalation therapy device according to the invention, reference is made to the fact that in Switzerland, approximately 550 children are born each year before reaching the 35th week of pregnancy, and thus potentially have an immature lung for which surfactant replacement therapy is advisable. In other countries, for example in Germany, ten times as many premature babies can be expected.
Surfactant replacement therapy occurs whilst the premature babies/infants are in so-called incubators, i.e. in an environment with controlled temperature and humidity since the premature babies are not yet able to maintain their own body temperature. The surfactant is directly instilled into the trachea in liquid form via a tube. Intubation itself carries various risks, for example injury to the glottis or the trachea, pneumothorax, etc. Furthermore, mechanical ventilation, which generally accompanies instillation, can lead to additional damage to the lungs. However, many premature babies/infants make sufficient respiratory effort of their own and do not need to be intubated against this background. However, in order to deposit the surfactant in the lungs, intubation is the means of choice for instillation of the surfactant.
Whereas surfactant replacement therapy has been researched intensively and is already being widely used, nebulisation of the surfactant is problematic since the surfactant often has a low surface tension, a viscosity that is unfavourable for nebulisation and a tendency to foam. The physical properties of the surfactant have led to almost no consideration being given to nebulisation and administration of the surfactant in the form of an aerosol. Furthermore, a surfactant is generally very expensive, and thus the high deposition losses often observed during aerosol therapy have led to this manner of administering a surfactant not being researched further.
Against this background, the present invention aims to disclose a way of administering surfactant to premature babies and infants as part of an aerosol therapy.
This aim is achieved with an inhalation therapy device having the following features:
The invention combines three essential aspects for the particular field of use, namely the precise generation of an aerosol particularly suitable for administration to premature babies and infants, the application of a slight (optionally pulsatile) positive pressure to the airways/lungs in accordance with the CPAP/BIPAP principle, and the largely loss-free supply of an aerosol via a tapering nebulising chamber and an intubation tube which is expediently designed for this use, in which the nebulising chamber ends. It must furthermore be taken into consideration that owing to the fact that it is possible to realise overall very small distances and dimensions relating to the nebulising chamber, only a very small dead volume advantageously exists. The aerosol to be administered is thus available very early on at the start of a respiratory cycle and reaches deep into the airways and lungs of the child.
An inhalation therapy device according to the invention is therefore, however, also basically suitable for other uses.
It may thereby be expedient to adapt the dimensions, in particular of the intubation tube.
As can be seen from the description below, further aspects can be added in order to improve efficiency and effectiveness. Reference is made in this regard in particular to the heating and humidifying of the respiratory air, to the application of a pressure oscillation to the respiratory air flow, to the heating of the liquid to be nebulised and to the sheath-like flow surrounding the generated liquid droplets.
The invention will be described in more detail in the following by means of embodiments. Reference is thereby made to the figures, in which
a shows an enlarged view of a part of the embodiment according to
Provided in the embodiment of an inhalation therapy device according to the invention as shown in
In view of the use in premature babies and infants, the size of the liquid droplets (MMD) in an inhalation therapy device according to the invention is between 1.5 and 3 μm. These guidelines can be adhered to with a particularly high degree of accuracy in an aerosol generating device 1 comprising an aerosol generator 11, as already addressed above, with a membrane 13 for generating liquid droplets. An aerosol generating device having a membrane aerosol generator is thus a preferred embodiment of the invention.
The embodiment of an inhalation therapy device according to the invention as shown in
A maximum pressure of 4 to 7 mbar and a tidal volume of approximately 5 ml per kg of body weight are to be used as suitable guidelines for premature babies and infants. Adhering to these guidelines, ventilation of the premature babies/infants is carried out against the background of the ability to breathe independently in accordance with the CPAP principle (Continuous Positive Airway Pressure). The ability of the patient to breathe is always a requirement for the use of CPAP ventilation, however in premature babies and infants, it is advantageously achieved owing to the CPAP positive pressure that the lungs are inflated slightly in advance and the collapse of already ventilated alveoli is prevented. Other methods, such as, for example, according to the BIPAP principle (Biphasic Positive Airway Pressure) can also be used. The pressures that can be applied are dependent on the specific circumstances and can reach, and even exceed, values of 10 mbar (CPAP) and 15 mbar (BIPAP).
The embodiment of an inhalation therapy device according to the invention as shown in
Supply of the respiratory air flow 4 takes place via a respiratory air supply opening 51 of the nebulising chamber 5, at which the supply line 32 of the respiratory air flow generating means 3 is disposed. Supply preferably takes place in such a manner that a turbulent flow forms when the respiratory air 4 enters the nebulising chamber 5. It is ensured in this manner that there is a potential lack of flow through only minimal dead spaces of the nebulising chamber 5 close to the respiratory air supply opening 51, whereby ensuring the best possible supply of oxygen-containing fresh air to the premature/newborn baby. However, the turbulent flow generally ensures that there is flow though the entire or almost the entire nebulising chamber 5. As will be explained below, means are provided in a preferred embodiment of the invention, which convert the turbulent flow into a largely directed flow.
The liquid droplets 2 and the respiratory air 4 mix in the nebulising chamber 5 and, as shown in
According to the invention, the embodiment shown in
In order to ensure a largely deposit-free transport of the liquid droplet/respiratory air mixture through the intubation means, a tube having an inner diameter of 2 to 3.5 mm is expediently used. To again minimise deposition losses, the entire length of the tubular intubation means should not exceed 50 cm. Very good results, which could not be expected in view of the passages for the aerosol that seem comparatively small, are surprisingly achieved if these guidelines are adhered to. This is all the more true in the case of a surfactant as the liquid to be nebulised, whose physical properties do not give rise to the anticipation that if certain guidelines are adhered to and suitable nebulisation is carried out, an aerosol administration of a surfactant to premature babies and infants is possible by way of inhalation.
The second end of the intubation means 6 is designed for endotracheal/endopharyngeal intubation, with design being advantageously carried out according to the invention such that in the case of orotracheal intubation via the mouth, the second end can be positioned behind the vocal folds of the patient, and in the case of nasopharyngeal intubation via the nose, the second end can be positioned behind the nasal cavity in the pharynx of the patient. Owing to the position-ability according to the invention of the second end 6b of the tubular intubation means 6, it is ensured that the liquid droplet/respiratory air mixture conveyed via the intubation means arrives behind the respective regions of the respiratory tract of the patient which carry out intense filtering. In the case of application via the nose, it is necessary to bridge the nasal area and release the liquid droplet/respiratory air mixture in the pharynx of the patient, whereas in the case of application via the mouth, the liquid droplet/respiratory air mixture is preferably released behind the glottis. As regards the design of the intubation end 6b according to the invention, emphasis is consequently on the length of this area since the length of the second end 6b of the intubation means 6 determines at which point of the patient's respiratory tract the liquid droplet/respiratory air mixture (of the aerosol) is released. In premature babies and infants, a length of approximately 15 cm is expedient.
Owing to the cooperation of the individual components of the inhalation therapy device according to the invention as shown in
It is thus possible, as mentioned above, to administer surfactant to premature babies and infants using an inhalation therapy device according to the invention. Surfactant reduces the surface tension in the alveoli and thus makes breathing easier for the children, which leads to an improved oxygen uptake. The positive effect of treatment with-surfactant is frequently described in literature. However, the administration of a surfactant aerosol that can be administered by means of the inhalation therapy device according to the invention is not known. This possibility is created by the invention since the overall concept of the inhalation therapy device according to the invention, which consists of several aspects, leads to the provision of a therapy device which makes it possible to administer a surfactant in this manner.
It must be stated with regard to the embodiment shown in
In order to assist conversion of the respiratory air flow into a largely laminar flow, the through-holes 16 can be equipped with respiratory air guides 16a, as is shown in
Provided in the second embodiment, as shown in
The respiratory air heating means 33 is preferably controlled by the respiratory air control apparatus 34 in such a manner that the respiratory air supplied to the patient via the intubation means is heated to 35° C. to 37° C. The respiratory air control apparatus 34 controls the temperature of the respiratory air so that it is within a narrow range irrespective of the external conditions. The respiratory air control apparatus 34 can thereby be connected with the air conveying means 31 and can control its ventilator in consideration of the measured values supplied to the respiratory air control apparatus 34 by measuring sensors 35, 35′ and/or 35″.
Finally, a connection between the aerosol generating device 1, more precisely the controller 14 thereof, and the respiratory air control apparatus 34 may be expedient so that the start of nebulisation of the liquid is taken into consideration when controlling the respiratory air heating means 33. The reason for this is that owing to the generation of the liquid droplets 2 in the nebulising chamber 5, cooling of the respiratory air that is present in the nebulising chamber 5 and mixes with the liquid droplets occurs since the liquid droplets are dried by the respiratory air. This drying effect is basically desirable since it is thereby possible to influence the size of the liquid droplets so that the guidelines (see above) can be complied with more accurately. By way of an appropriate control of the heating means 33, it is thus ultimately possible to set the temperature and droplet size (by controlled drying) of the aerosol, in particular if a sensor 35″ is placed in the vicinity of the outlet 53 of the nebulising chamber 5. A heating means for the liquid stored in the aerosol generator, which heats the stored liquid, can be provided as a supportive measure. The heating means is preferably controlled by the controller 14.
As an alternative or in addition to the respiratory air heating means 33 shown in
As a modification of the first embodiment, the inhalation therapy device according to the invention in
Prominent in the fourth embodiment is the respiratory air pulsation means 70, shown in
The pulsation means 70, which is schematically shown in
In accordance with this aspect,
As can be seen from all of the figures and the embodiments shown therein, the inhalation therapy device according to the invention comprises an aerosol generating device 1, a respiratory air flow generating means 3 and a nebulising chamber 5 to which a tubular intubation means 6 is connected. The nebulising chamber 5 not only comprises a tapering area that ends in the intubation means, but rather also allows the mixing of the supplied respiratory air 4 and the liquid droplets 2, which are supplied to the nebulising chamber 5 by the respiratory air flow generating means 3 and the aerosol generating device 1, respectively. In a particularly advantageous design shown in
In the above description of the invention, reference was made in particular to the administration of a surfactant. However, it is also apparent from the description of the invention that an inhalation therapy system according to the invention is basically suitable for the inhalational administration of medicaments of any type, in order to provide newborn or premature babies with a topical or systemic medicinal therapy using the inhalation therapy system according to the invention, characterised in that bodily functions and/or an unnatural or abnormal state are transformed back into a normal state and suffering is alleviated or cured.
The medicinal therapy is characterised in that using the inhalation therapy system according to the invention, medicaments of any type and class from animal, bacterial, human or synthetic material can be administered particularly advantageously by way of inhalation, such as, for example,
These substances can be used in the form of acids or alkalis as pharmaceutically common salts or complexes, prodrugs or their optically active antipodes, stereoisomers, enantiomers alone or in combinations.
Particularly suitable medicament formulations are characterised in that they can be nebulised as aqueous preparations in volumes of 0.3 to 10 ml and particularly preferred in volumes of 0.5 to 5 ml, and, with the inhalation therapy system according to the invention, an aerosol having a mass median diameter (MMD) of less than 5 μm, particularly preferred of less than 3.5 μm, and a narrowband particle distribution can be generated, which is distinguished by a geometric standard deviation of less than 2 and particularly preferred of less than 1.6, whereby an in vitro lung dose of >20% and particularly preferred of >25% is achieved in a cast model, which is more than those of conventional inhalation therapy systems with jet nozzle nebulisers.
The inhalational medicament therapy using the innovative inhalation therapy system is characterised in that respiratory clinical symptoms, such as infantile pulmonary diseases, pulmonary distress symptoms, asthma, obstructive bronchitis, bacterial and non-bacterial inflammations, coughs, pulmonary hypertension, parenchymal diseases, genetic defects such as, for example, mucoviscidosis, infantile diabetes, etc., can preferably be treated therewith.
From another perspective, the inhalation therapy system according to the invention can be deemed suitable for the improved inhalational administration of medicaments using an innovative nebuliser concept, which is adapted, in particular, to the requirements of the treatment of premature babies and also normal infants.
In order to achieve a particularly high efficiency, the administration of medicaments can take place using different administration strategies. Since the administration strategy suitable for a particular case depends on various limiting conditions, e.g. on the medicament or medicament combination to be administered, on the structural details of the inhalation therapy system, on the patient group to be treated, etc., a representative example will be explained in the following, which portrays in more detail a field that can be influenced by an administration strategy. Against the background of experimental results showing that if an output rate of the aerosol generator is too high, efficiency is lower than in the case of a reduced output rate, an administration strategy which takes these results into account is suitable. Reduction or adjustment of the output rate of the aerosol generator is essential for the administration strategy explained here as an example, as a result of which the administration strategy leads to increased efficiency. The reduction/adjustment of the output rate can be achieved in a particularly flexible manner by alternately switching on/off the aerosol generator since the output rate can be determined (set) in wide ranges by adjusting/modifying the on/off switching phases.
In order not to compromise the effectiveness of the therapy or to cause a delayed onset thereof, a phase with an increased output rate can precede the phase with a reduced output rate in a specific design of the administration therapy. It is thereby accepted that the efficiency during this preceding phase is lower and a greater amount of medicament must be used than is the case with an optimised output rate. However, it can be achieved by means of the intentionally increased output rate having lower efficiency that the desired effect of the medicament commences at a desired earlier point in time than could be achieved in the case of administration with a reduced output rate from the outset. A reduced output rate can be used with an optimising effect as regards the utilisation of the active substance (=efficiency of administration, minimised loss of active substance in the system). It is obvious that an effective therapy can be combined very flexibly with high efficiency and effectiveness by means of suitable administration strategies.
This aspect shall be explained again in an exemplary manner using the example of the aforementioned surfactant. If, in a first phase of the administration strategy, the surfactant is administered to the premature baby at a high output rate using the inhalation therapy system according to the invention, the stabilising effect of the surfactant on the lungs and an improvement in lung function will be rapidly achieved. Once the lung function of the premature baby has stabilised, the output rate can be reduced in a second phase of the administration strategy with the aim of now optimising use of the surfactant in respect of efficiency, whereby achieving improved utilisation of the valuable active substance, which does not only have to be the aforementioned surfactant.
It is very obvious that a membrane nebuliser is exceptionally suitable as an aerosol generator for implementing the administration strategy explained above. The reason for this is that a membrane nebuliser can be switched on and off in a particularly suitable manner by way of the activation signal to the piezo-oscillator that causes the membrane to oscillate. The pulsed operation, in which aerosol generating phases alternate with resting phases, can be realised very precisely and without any problems. Optimisation for each expedient/required administration strategy can be realised and optimised in this manner.
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