A non-invasive phototherapy device for the treatment of respiratory distress syndrome in infants and adults and for surfactant production

Abstract

The invention relates to a non-invasive phototherapy device for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults, and in the in vivo / in vitro surfactant production. In the non-invasive device of the invention, the non-invasive application is performed outside the body using an infrared LED or laser light source at adjustable treatment durations. In the device of the invention, some complications emerging due to surfactant and the administration route of the surfactant during the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults are prevented. The device of the invention provides a non-invasive treatment of Respiratory Distress Syndrome (RDS) in both infants and adults. The invention provides a non-invasive device, which is inexpensive, feasible and safe for use by families at home, for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults.

Description

[0001] A NON-INVASIVE PHOTOTHERAPY DEVICE FOR THE TREATMENT OF RESPIRATORY DISTRESS SYNDROME IN INFANTS AND ADULTS AND FOR SURFACTANT PRODUCTION

[0002] Technical Field of the Invention

[0003] The invention relates to a non-invasive phototherapy device for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults, and in the in vivo / in vitro surfactant production.

[0004] State of the Art

[0005] Respiratory distress syndrome is one of the most common and important diseases of premature newborns. Respiratory Distress Syndrome (RDS) is a respiratory distress syndrome caused by lung immaturity and surfactant deficiency. In other words, RDS is caused by the inability to produce surfactant due to insufficient lung development in premature newborns. Surfactant is a surface tension activator that keeps the lung alveoli open. Classically, it is a disease characterized by tachypnea, dyspnea, intercostal retractions, moaning, nasal breathing, cyanosis and increased oxygen demand in infants beginning in the first hours after birth. RDS and related complications constitute the most important cause of mortality and morbidity in premature infants[1]. RDS in premature newborns is a picture of pulmonary insufficiency that begins at birth or within a short period of time after birth and progressively worsens in the first two days of life. RDS is still a disease that can result in serious morbidity and mortality for premature infants despite significant advances in its treatment. The frequency of RDS increases with decreasing gestational age. The infants born before the thirtieth week of gestation have a high risk of RDS. In a study conducted by the Turkish Neonatology Society in 2016-2017, the incidence rate was 70.3% below 32 weeks and 86.5% at 28 weeks and below. Acute Respiratory Distress Syndrome (ARDS) is an acute, life-threatening condition covering both lungs, characterized by capillary endothelial damage, diffuse pulmonary infiltration and hypoxemia resistant to oxygen therapy[2]. In the state of the art, surfactant, which is a surface tension activator that keeps the lung alveoli open in patients with Respiratory Distress Syndrome (RDS), is of great importance and frequently used to reduce mortality and morbidity. Surfactant can be administered through a catheter during nasal ventilation with the INSURE method (intubate, give surfactant, extubate), LISA (Less Invasive Surfactant Administration) or MIST (Minimally Invasive Surfactant Therapy) method when failure develops in infants on nasal mode support. Although MIST and LISA methods are less invasive methods, studies on pharyngeal instillation, laryngeal mask, nebulizer and surfactant applications as non-invasive application methods are still ongoing[3]. In the state of the art, surfactant preparations are mainly divided into two groups: natural and synthetic. Natural surfactant preparations are derived from pig, bovine and calf lung extracts. Synthetic preparations comprise only phospholytes, while new generation preparations also comprise recombinant surfactant proteins or synthetic peptides. Natural (animal- derived) surfactants are said to be more effective in preventing air leakage and mortality. Surfactant should be administered in the neutral position with attention to aseptic methods. The patient should be closely monitored during and after surfactant administration. The patient should be closely monitored for obstruction in the endotracheal tube, apnea, desaturation, bradycardia, tachycardia, surfactant reflux, volutrauma, pulmonary hemorrhage, surfactant going to one lung, pneumothorax, patent ductus arteriosus and increased need for treatment. Tracheal aspiration should not be performed for 1-6 hours after application. In premature infants, the target saturation should be 90-94%. Exogenous surfactant administration can also be applied to the newborns with refractory pulmonary hypertension, mecaonium aspiration syndrome, neonatal pneumonia and brochiolitis, congenital diaphragmatic hernia, pulmonary hemorrhage and bronchopulmonary dysplasia, in addition to premature infants[3]. In conclusion, surfactant administration is an invasive procedure, whether it is a natural or synthetic preparation. Surfactant preparations can be administered to the newborn infant invasively with the help of an endotracheal tube. Apart from the invasive administration of surfactant by endotracheal tube, less invasive methods such as aerosolization, nebulization or in utero, laryngeal mask and catheter insertion into the trachea without direct intubation are still in the experimental stage[3]. In addition, some complications may develop depending on the route of administration and surfactant. The currently most commonly used route of administration of surfactant preparations is endotracheal tube. Endotracheal tube placement is known to have side effects such as secretion aspiration, esophageal intubation, ventricular arrhythmia, dangerous agitation, cardiovascular collapse, hypoxemia, cardiac arrest and death. Less invasive methods have the same side effects but only slightly fewer. In addition, the invasive surfactant applications cannot be performed in every healthcare institution, but can be performed in well-equipped hospitals with intensive care units and under sterile conditions[5].

[0006] Side effects of exogenous surfactant use include bradycardia, hypoxemia, a rapid change in gas exchange followed by dramatic changes in static pulmonary compliance and blockage of the endotracheal tube, and insufficient surfactant material reaching the alveoli. The frequency of pulmonary hemorrhage may increase after surfactant therapy. In the long term, circulating immune complexes directed against surfactant proteins have been reported in these infants. It has also been reported that the caution should be taken in surfactant preparations in terms of microbiological safety[5]. This situation prolongs the length of hospitalization of infants in intensive care, increases the cost of care for infants, and leads to social and physiological trauma for the family and the newborn infant.

[0007] In the patent document no. US10293023B2, which is in the state of the art, there is a device for use in the treatment of Respiratory Distress Syndrome, which arranges the active cell-cell junction integrity of the extracellular matrix (extracellular matrices, ECM) by physical changes and thus regulates vascular tension.

[0008] Due to the reasons such as limitations and inadequacies of devices for use in the treatment of Respiratory Distress Syndrome (RDS) in the state of the art, insufficient quantity the surfactant applied by the used methods reaching the lungs, adverse effects due to invasive surfactant administration, including bradycardia, hypoxemia, dramatic changes in static pulmonary compliance following rapid changes in gas exchange, and blockage of the endotracheal tube, adverse effects from invasive endotracheal tube insertion such as secretion aspiration, esophageal intubation, ventricular arrhythmia, dangerous agitation, cardiovascular collapse, hypoxemia, cardiac arrest and death, the fact that these limitations, inadequacies, complications and side effects are due to the fact that surfactant applications are invasive procedures regardless of natural or synthetic in the current technique, and the fact that this situation brings some complications and in addition, these complications prolong the length of stay of the infants in the intensive care unit, it has become necessary to introduce a device for use in the treatment of Respiratory Distress Syndrome (RDS) in which all these problems are eliminated.

[0009] Summary and Objects of the Invention

[0010] In the invention, a non-invasive phototherapy device for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults, and in the in vivo / in vitro surfactant production is described.

[0011] An object of the invention is to provide a non-invasive treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults. In the invention, the infrared light delivered to the patient outside the skin increases endogenous surfactant production, allowing the disease to heal rapidly in its natural course. The non-invasive treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults is enabled by the photobiomodulation effects (enhancing cell growth and regulating cell damage repair) of the infrared light on biological tissues in the invention. In the non-invasive device of the invention, the non-invasive application is performed outside the body using an infrared LED or laser light source at adjustable treatment durations.

[0012] Another object of the invention is to provide a non-invasive device in which some complications emerging due to surfactant and the administration route of the surfactant during the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults are prevented. These complications are prevented by the photobiomodulation effects (enhancing cell growth and regulating cell damage repair) of infrared light applied externally to biological tissues in the non-invasive device of the invention.

[0013] Another object of the invention is that the same method can be applied naturally on bovine and porcine lungs or lung cells by infrared light with the photobiomodulation method, resulting in less animal waste and more surfactant production. In other words, the surfactant production is increased in the laboratory environment. The device of the invention provides a non-invasive treatment of Respiratory Distress Syndrome (RDS) in both infants and adults. The fact that the device of the invention enables the non-invasive treatment of Respiratory Distress Syndrome (RDS) in both infants and adults is provided by the small version of the device that can be used for infants and the dose-adjusted large version that can be used for adults, wherein the device acts by photobiomodulation in the invention. There are even experimental and laboratory versions of the invention that can be applied to cells and tissues.

[0014] The invention provides a non-invasive device, which is inexpensive, feasible and safe for use by families at home and in every health institution, for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults. The safe use of the device of the invention is ensured by electrical isolation control circuits, cooling blocks / circuits to absorb the heat generated and timer circuits with application time setting. The application of infrared light with the photobiomodulation technique used in the device of the invention makes it possible to increase surfactant production in the laboratory and provides a safe non- invasive method and device that can be used in RDS diseases seen in premature infants or other newborns and ARDS diseases in adults.

[0015] In the device of the invention, there is no invasive intervention to the patient and no substance or material is invasively delivered into the body. The patient is illuminated from a certain distance, i.e. outside the body, with a non-ionizing infrared LED / laser that covers certain wavelengths. It is known that the remote infrared light does not harm biological systems at certain doses and durations. The infrared light to be provided with the device increases endogenous surfactant production, allowing the disease to heal rapidly in its natural course. The method and technique used in the device of the invention do not have any side effects and complications at the doses and durations applied. In addition, while the existing methods can only be applied in hospitals with intensive care and equipped hospitals and only under sterile conditions, the device of the invention and the method and technique related to the device can be applied in every health institution. In addition, the device of the invention can even be applied at home by families under the supervision of a physician. The device of the invention can be used in adult pneumonia, meaning that it can also be adapted to ARDS syndromes and can be easily applied. Another positive aspect of the device of the invention is that the device can be adapted for use in the production and reproduction of organic surfactants in experimental and laboratory environments, either in vivo or in vitro. This enables the production and reproduction of surfactant in the laboratory. Organic surfactant preparations used in the invasive or less invasive surfactant applications of the device of the invention comprise surfactant B and C. However, the surfactant A, B, C, D are produced in human lung alveoli and the surfactant A and D are involved in cellular phagocytosis and cellular defense activities. The device of the invention is very important in cleaning cellular waste and fighting infections in RDS and ARDS diseases. The non-invasive photobiomodulation technique used in the device of the invention also enables the endogenous production of all forms of surfactant (A, B, C, D) in the alveoli.

[0016] Description of the Drawings

[0017] Fig. 1 Infant and adult treatment model.

[0018] Fig. 2 Surfactant production model in the cell.

[0019] Fig. 3 Control panel in treatment, cell and experimental model.

[0020] Fig. 4 Oven cooling system in the surfactant production model in the cell.

[0021] Fig. 5 Laser experimental application model.

[0022] Fig. 6 LED experimental application model.

[0023] Description of the References in Figures

[0024] 1 . Light source

[0025] 2. Aluminum cooling mini block / blocks

[0026] 3. Eye and face protection screen

[0027] 4. Hinge

[0028] 5. Porous bottom plate

[0029] 6. Remote and control panel

[0030] 7. Cell container cover

[0031] 8. Multiple cell container 9. Microcontroller circuit

[0032] 10. Display

[0033] 11 . Direct current power supply

[0034] 12. Relay circuit

[0035] 13. RTC module

[0036] 14. Fans

[0037] 15. Radiator

[0038] 16. Liquid storage tank and hose

[0039] 17. Pump

[0040] 18. Laser

[0041] 19. LED / laser lens

[0042] 20. Foot

[0043] 21 . Driver circuit

[0044] Detailed Description of the Invention

[0045] The invention relates to a non-invasive phototherapy device for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults, and in the in vivo / in vitro surfactant production. In the non-invasive device of the invention, the non-invasive application is performed outside the body using an infrared LED or laser light source at adjustable treatment durations. In the device of the invention, the complications emerging due to surfactant and the administration route of the surfactant during the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults are prevented. The device of the invention provides a non-invasive treatment of Respiratory Distress Syndrome (RDS) in both infants and adults. The invention provides a non-invasive device, which is inexpensive, feasible and safe for use by families at home, for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults.

[0046] A non-invasive device of the invention for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults, and in the in vivo / in vitro surfactant production comprises

[0047] • a light source (1 ), • 2 driver circuits (21) that operate the light sources stably by supplying constant current to the light sources,

[0048] • a LED / laser lens (19) for the photomodulation function in treatment and experimental studies,

[0049] • a microcontroller circuit (9) that manages the operation of the device,

[0050] • a touch display (10) as an interface for the user to control the device,

[0051] • a direct current power supply (11 ) that supplies electricity to the circuits,

[0052] • at least 4 feet (20) for the delivery of LED and laser light from a distance of 1 -50 cm.

[0053] Here, said light source (1) is LED or laser.

[0054] In an embodiment of the invention, a non-invasive device of the invention for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults, and in the in vivo / in vitro surfactant production comprises

[0055] • 2-500 light sources (1 ) with a wavelength of 630-1070 nm,

[0056] • 2 driver circuits (21) that operate the light sources stably by supplying constant current to the light sources,

[0057] • 2-500 LED / laser lenses (19) for the photomodulation function in treatment and experimental studies,

[0058] • a microcontroller circuit (9) that manages the operation of the device,

[0059] • a touch display (10) as an interface for the user to control the device,

[0060] • a direct current power supply (11 ) that supplies electricity to the circuits,

[0061] • at least 4 feet (20) for the delivery of LED and laser light from a distance of 1 -50 cm.

[0062] Here, said light source (1 ) is LED or laser.

[0063] The form of the device of the invention to be used for experimental animals, newborn infants and adults is equipped only with aluminum cooling blocks. The laboratory form of the device of the invention is equipped with a liquid cooling system module for stable operation in closed, extremely hot and humid environments. This liquid cooling system module consists of an aluminum liquid cooling block, a radiator (15), radiator fans (14), a direct current power supply (11 ), a pump (17), a liquid storage tank and hose (16). The cooling block is arranged close to the light sources (1 ), which generate heat energy. The cooling block is responsible for taking the heat from the liquid passing therethrough and transporting it to the radiator (15). The hot liquid transported to the radiator (15) is cooled by the radiator fan (14). Thanks to the pump (17) and hose (16), the cooling process is carried out by advancing the coolant in the closed system.

[0064] An operation method for the non-invasive device of the invention for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults, and in the in vivo / in vitro surfactant production comprises the process steps of i. receiving the user’s treatment commands from the touch display (10) and transmitting them to the microcontroller circuit (9), ii. calculating the start and end time of the treatment with the time information received from the real time clock circuit by the microcontroller circuit (9), iii. triggering the switching element by the microcontroller circuit (9), iv. after triggering, transmitting electricity to the drive circuit (21 ) by the relay circuit (12), thereby energizing the drive circuit (21 ), v. regulating the electricity and producing a constant current by the energized driver circuit (21 ), vi. transmitting the constant current generated to the light source (1) and realizing the light exposure (illumination) required for the treatment, vii. terminating the microcontroller circuit (9) at the specified end time.

[0065] Said light source (1 ) here is a LED or laser; in addition, the wavelength of said light source (1) is in the range 630-1070 nm. In addition, a total of 2-500 light sources (1) are used.

[0066] References

[0067] [1] Qekilmez E. K, Yildizba§ HY, Ozlu F. (2013, December 1). Respiratuar distres Sendromu Ve Komplikasyonlan. Ar§iv Kaynak Tarama Dergisi.

[0068] [2] Diamond M, Peniston Feliciano HL, Sanghavi D, Mahapatra S. Acute respiratory distress In: StatPearls. [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 .

[0069] [3] Sweet DG, Turner MA, Stranak Z, Plavk, R, Clarke P, Stenson BJ, Singer D, Goelz R, Fabbri L, Varol, G, Piccinno A, Santoro D, Spee, CP. 2017. “A first-in-human clinical study of a new SP-B and SP- C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome", Arch Dis Child Fetal Neonatal Ed., 102(6), F497-F503.

[0070] [4] Kultursay N, Uygur O, Yalaz M. (2014 1) Yenidogan doneminde surfaktan kullanimi-bilinenler, halen ara§tinlanlar, ara§tinlmasi gerekenler. Turk Pediatri Ar§ivi.

[0071] [5] Gundogan K, Co§kun R, Guven M, Sungur M. (2011, Eylul 1). Yogun Bakimda Endotrakeal Entubasyon Komplikasyonlan. Yogun Bakim Dergisi.

Claims

CLAIMS1 . A non-invasive phototherapy device for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults, and in the in vivo / in vitro surfactant production, characterized in that it comprises• a light source (1),• 2 driver circuits (21) that operate the light sources stably by supplying constant current to the light sources,• a LED / laser lens (19) for the photomodulation function in treatment and experimental studies,• a microcontroller circuit (9) that manages the operation of the device,• a touch display (10) as an interface for the user to control the device,• a direct current power supply (11) that supplies electricity to the circuits,• at least 4 feet (20) for the delivery of LED and laser light from a distance of 1-50 cm.

2. A non-invasive phototherapy device according to claim 1 , characterized in that it comprises• 2-500 light sources (1 ) with a wavelength of 630-1070 nm,• 2 driver circuits (21) that operate the light sources stably by supplying constant current to the light sources,• 2-500 LED / laser lenses (19) for the photomodulation function in treatment and experimental studies,• a microcontroller circuit (9) that manages the operation of the device,• a touch display (10) as an interface for the user to control the device,• a direct current power supply (11) that supplies electricity to the circuits,• at least 4 feet (20) for the delivery of LED and laser light from a distance of 1-50 cm.

3. A non-invasive phototherapy device according to claim 1 or 2, characterized in that said light source (1) is LED or laser.

4. An operation method of a non-invasive phototherapy device for use in the treatment of Respiratory Distress Syndrome (RDS) in preterm infants and Acute Respiratory Distress Syndrome (ARDS) in adults and in the in vivo / in vitro surfactant production, characterized in that it comprises the process steps of i. receiving the user’s treatment commands from the touch display (10) and transmitting them to the microcontroller circuit (9), ii. calculating the start and end time of the treatment with the time information received from the real time clock circuit by the microcontroller circuit (9), iii. triggering the switching element by the microcontroller circuit (9), iv. after triggering, transmitting electricity to the drive circuit (21) by the relay circuit (12), thereby energizing the drive circuit (21), v. regulating the electricity and producing a constant current by the energized driver circuit (21 ), vi. transmitting the constant current generated to 2-500 LED or laser light sources (1 ) with a wavelength of 630-1070 nm and realizing the light exposure (illumination) required for the treatment, vii. terminating the microcontroller circuit (9) at the specified end time.

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