Title of Invention	"A table-top drug-delivery apparatus for alveolar drug delivery for prevention & management of primary & secondary forms of pulmonary hypertension"
Abstract	A table-top drug-delivery apparatus for alveolar drug delivery is disclosed. The apparatus comprises an aerosol generator, a reservoir having an inlet end and an outlet end, a nebuliser for containing medicament located at or connected to said reservoir at said inlet end thereof, said nebuliser being connected to said aerosol generator, so that when the aerosol generator is in an operative state, it causes said medicament in said nebuliser to be converted into fine droplets and deliver it to the inlet end of said reservoir, a mouth piece connected to said outlet end of said reservoir for receiving said fine droplets of the medicament, the inlet end and outlet end being so positioned that the time lag between receiving the nebulised medicament at the inlet end and delivery thereof to said outlet end is between 30 to 90 seconds so that fine droplets of said nebulised medicament of suitable for use as pulmonary dose are created and delivered to said mouth piece.

Title of Invention

"A table-top drug-delivery apparatus for alveolar drug delivery for prevention & management of primary & secondary forms of pulmonary hypertension"

Abstract

A table-top drug-delivery apparatus for alveolar drug delivery is disclosed. The apparatus comprises an aerosol generator, a reservoir having an inlet end and an outlet end, a nebuliser for containing medicament located at or connected to said reservoir at said inlet end thereof, said nebuliser being connected to said aerosol generator, so that when the aerosol generator is in an operative state, it causes said medicament in said nebuliser to be converted into fine droplets and deliver it to the inlet end of said reservoir, a mouth piece connected to said outlet end of said reservoir for receiving said fine droplets of the medicament, the inlet end and outlet end being so positioned that the time lag between receiving the nebulised medicament at the inlet end and delivery thereof to said outlet end is between 30 to 90 seconds so that fine droplets of said nebulised medicament of suitable for use as pulmonary dose are created and delivered to said mouth piece.

Full Text	Field of the Invention The present invention relates to a table-top drug-delivery apparatus used for the prevention and management of primary and secondary forms of pulmonary hypertension, all conditions afflicting pulmonary microvasculature and pulmonary parenchyma. Background of the Invention Pulmonary hypertension Pulmonary hypertension can be primary (cause unknown) or secondary to a number of lung diseases. Primary pulmonary hypertension has no successful treatment and leads to mortality in the long run. Secondary pulmonary hypertension almost always complicates a number of diseases that lead to alveolar hypoxia. The present medical management appears inadequate to meet the challenge of this common and frequently a fatal or uncontrolled problem. One of the main treatment modalities is systematically delivered vasodilators. Drugs like prazoin, nifedipine, phentolamine and sildenafin are among the variety of drugs tried for the purpose. The main problem with systematic delivery is that a high dosage in the circulation is required for the desired effect because the drug is distributed throughout the body fluids but beneficial effect is limited to the target organ-microvasculature of the lungs. The high dosage required in the blood limits the use of this treatment as use of such high dosages causes serious side effects like low blood pressure, significant palpitation and heart problems. Further, this limits the duration of treatment only in severe cases and that also for few days or weeks only, while most of the diseases with which pulmonary hypertension is associated are chronic and mild in nature and may require treatment for years or even for life. There may not be any benefit at all if regional blood supply is blocked significantly due to thrombosis in the lung microvasculature. Systematic vasodilators are therefore now considered an inadequate treatment in pulmonary hypertension but continue to be given in absence of a better treatment choice. Other methods of treatment include oxygen inhalation (with or without 5% CO2), Nitric Oxide inhalation therapy, and compressed/ hyperbaric air administration. However, these therapies can only be given for short periods in time of emergency. Secondly, these are costly and mostly require infrastructural facilities for continuous administration. Thirdly, they almost immobilize the patient for the duration of the therapy. Thus, though highly effective, these therapies are useful only as hospital-based treatment for a short period. Inhalable aerosols of vasodilating substances have not been used for treating pulmonary hypertension clinically. The main cause of this has been the inability of the commercially available aerosol/nebulizer/dispersion systems to deliver pharmacological dose to the pulmonary level. These systems are basically designed to act at bronchi-trachea level and are not useful for managing pulmonary hypertension. Drugs acting locally in alveolar space Apart from pulmonary hypertension, there are many other diseases that affect pulmonary tissue causing hypoxic hypoxemia and problem in oxygen transfer to blood. These include widespread infection (viral, bacterial or fungal), acute inflammations (diffuse bronchiolitis/alveolitis/ ARDS/allergic conditions) or chronic inflammations (all lung conditions leading to fibrotic changes), such as interstitial lung diseases and cancers. All these require higher concentration of drugs like antibiotics, antiviral substances, steroids, detergent/surfactants and anticancer drugs in the local space as compared to other tissues to enhance pharmacological effect and lower down side effects. For the same reasons as mentioned above systemic route and routine inhalation therapy is inadequate to meet the challenge though both continue to be used in absence of the better alternative. Systematically acting drugs routed through the lungs Recently, delivery through buccal mucosa and lungs has been initiated for which higher deposition of the drug in the alveolar space is advantageous. Wider use or higher success rate has not been possible till now because alveoli are not automatically the preferred site of deposition of drugs inhaled though various commercially available methods and devices. Considering the widespread nature of the disease (primary or secondary pulmonary hypertension), its fatal or incapacitating nature, and further considering the inadequacy of the present line of management with respect to control or cure, relief of symptoms, side effects, cost-effectiveness, patient comfort or availability, it is realized that a new treatment concept and methodology is urgently required. It is also realized that unconscious or highly breathless individuals may have some different requirements for inhalable drugs and routinely available methods and devices may not be sufficiently effective. Objects of the Invention It is therefore, an object of the present invention to provide a new drug-delivery system apparatus for treating or preventing primary or secondary pulmonary hypertension and any hypoxic hypoxemic states. It is another object of the present invention to provide a drug-delivery apparatus for depositing a higher amount of drug in the alveolar space for better pharmacological action. It is yet another object of the present invention to provide a drug-delivery apparatus that, upon combination with an air compressor and a nebulizer is capable of being used for prevention or treatment of the conditions as mentioned above, either independently or concurrently with other treatments, and can be used at home as well as hospital. It is yet another object of the present invention to provide a drug-delivery apparatus that is capable of being for aerosolization of drugs using commercially available respirable solutions. It is a further object of the present invention to provide a drug-delivery apparatus for treating pulmonary hypertension and hypoxic hypoxemia states that is reusable, lightweight, transportable, easily operable without much training and easy to dismantle and store. It is yet another object of the present invention to provide a drug-delivery apparatus for treating pulmonary hypertension and hypoxic hypoxemia states that does not require a big infrastructure for operation and can be used in remote places. Summary of the invention The above and other objects of the present invention are achieved by the apparatus of the present invention, which is based on the surprising finding that if the time lad between the formation of nebulised medicament and delivery thereof to the patient is maintained between 30 to 90 seconds, a perfect dosage suitable for pulmonary level is achieved. Accordingly, the present invention provides a table-top drug-delivery apparatus for alveolar drug delivery which comprises an aerosol generator, a reservoir having an inlet end and an outlet end, a nebuliser for containing medicament located at or connected to said reservoir at said inlet end thereof, said nebuliser being connected to said aerosol generator, so that when the aerosol generator is in an operative state, it causes said medicament in said nebuliser to be converted into fine droplets and deliver it to the inlet end of said reservoir, a mouth piece connected to said outlet end of said reservoir for receiving said fine droplets of the medicament, the inlet end and outlet end being so positioned that the time lag between receiving the nebulised medicament at the inlet end and delivery thereof to said outlet end is between 30 to 90 seconds so that fine droplets of said nebulised medicament of suitable for use as pulmonary dose are created and delivered to said mouth piece. In a preferred feature, said time lag is about 45 seconds. In a preferred feature, said nebuliser is connected to said aerosol generator by means of pre-connecting tubes. In a preferred feature, said reservoir is of a metal or a polymer. In a preferred feature, said polymer is a food-grade polymer. In a preferred feature, the capacity of the container is in the range of 1-50 litres. In a preferred feature, said reservoir has a volume in the range of 8-14 litres. In a preferred feature, the working output of the external air compressor is in the range of 1-50 litres/min. In a preferred feature, said reservoir has one or more further inlets receiving atmospheric or hot air. In a preferred feature, a gas mask or an oxygen source is connected between said outlet and said mouth piece. In a preferred feature, said outlet end is fitted with an air filter. In a preferred feature, the outflow portal or the outlet end is fitted with an air valve, preferably, one-way air valve. In a preferred feature, an air filter is are connected between said outlet end and mouth piece, said air filters having a maximum pore size of about 220 microns. Brief description of the accompanying Drawings Figure 1 illustrates a conventional apparatus used for inhalation of drugs. Figure 2 illustrates the novel drug-delivery apparatus according to the present invention. Description of the Invention The present invention relates to a novel drug-delivery apparatus for the management (prevention and treatment) of primary and secondary hypertension. Thus, the present invention is also beneficial in a number of lung diseases that include chronic obstructive airway disease and its variants, bronchial asthma, diffuse tuberculosis, emphysema, interstitial lung diseases, Adult Respiratory Distress Syndrome and pulmonary edema and various high altitude diseases associated with pulmonary hypertension. The present invention is also useful in the treatment of all conditions causing hypoxic hypoxemia. The mechanism of the apparatus is such that a majority of inhalable drug particles produced are significantly smaller than the preferred range presently available for treating asthma and asthma-like conditions. Referring to Figure 1, the conventional system used for the purpose of inhalation of drugs comprises of an external air compressor (1) which is connected to an atomizer (3) by means of pre-connecting tubes (2) for creating fine droplets containing the medicament. The atomizer (3) is further connected to the mouthpiece (6) via post-connecting tubes (5) to facilitate inhalation of the medicament by he patient. During usage of this apparatus, the drug is atomized and then inhaled by the patient through the mouthpiece via the post-connecting tubes. The main disadvantage of the conventional inhaler is that the droplets created by the nebuliser and delivered to the patient are of such size that they are more suited for treatment of conditions at bronchi-tracheal level and are incapable of delivering dose to the pulmonary level. Therefore, such conventional apparatus is found to be extremely wanting for the management of pulmonary hypertension. The present invention successfully addresses the problem associated with the prior art device. As shown in Figure 2, the device in accordance with the present invention comprises of a main body of the apparatus consists of a sealed container reservoir (13). The reservoir (13) is preferably of a volume ranging from 1-50 litres. In a preferred feature, the container (13) is capable of being compressed into a lesser volume for storage and transport purposes. The container may be metal or polymer-based and it is preferred that it is made from a flexible food grade polymer. The container (13) has an opening (not shown) that can be sealed on requirement and can be used for filling and servicing of the container (13). A standard nebulizer (12) is connected to or located inside said container (13) in an appropriately fixed position with the nebulizer's inflow portel (16) protruding out for connection to an external air compressor or power operated aerosol generator (10). The external air compressor or operated aerosol generator (10) preferably has a working output of 1-50 litres/min of hot or ambient temperature air. The nebulizer (12) preferably generates aerosols of size range 0.5-20 microns (MMAD). The container (13) has an outflow portal or delivery end (17) which is connected either to a fitting mouthpiece (15) or to a breathing mask or to oxygen carrying tubing, through post-connecting tubes and preferably through an air-filter. The delivery end is preferably fitted with a one-way air valve (not shown) operating in this range of air flow. The inflow portal (16) and the delivery end (17) are spaced in a manner so that the time taken for flow of the drug from the inlet (16) to the delivery end (17) through the container is in the range of 30-90 seconds, preferably 45 seconds. This surprisingly and most unexpectedly achieves a pharmacological dose to the pulmonary level and is extremely useful for managing pulmonary hypertension. One or more holes are preferably bored into the body of the container that can be used to draw in hot air or atmospheric air using appropriate attachments. The main body of the apparatus may be kept warm or hot by any other supportive apparatus. All the polymers used are preferably food grade polymers. To bring the drug-delivery apparatus to the functioning stage, the nebulizer (12) is filled with an appropriate drug solution and all the connections of the apparatus are hermetically sealed. Upon starting the air compressor or aerosol generator (10), the drug is released from the nebulizer (12) and the patient has to inhale it through the delivery end. The time lag between the inlet end (16) and delivery end (17) of the container (13) is in the range of 30 to 90 seconds which ensures that the size of the aerosols is efficacious for the treatment of pulmonary hypertension.. Exhalation may be performed into the delivery pipe or the atmosphere. In accordance with the preferred embodiment of the present invention, the sequence and methodology of the manufacture process may be changed in a manner not detrimental to the stability and efficacy of the medical product. An advantage of the present invention is higher local deposition and lower systemic dose. Thus the pharmacological effect is higher, systematic side effects are reduced and cost is reduced. Upon nebulization and inhalation, the nebulized drug is preferably delivered to the peripheral lung parenchyma, evading significant deposition in oropharynx, trachea, and stomach. These drugs include steroids, surfactants, antibiotics, antivirals, amongst others. Further, the apparatus of the present invention is advantageous in conditions where inhalation route is followed for administering drugs having systematic action. These drugs include proteins, peptides and hormones amongst others. The apparatus can also be operated upon unconscious or semiconscious patients and those with severe dyspnoea and can be managed at home along with or without other support systems. Certain quality control measures are embedded within the process of manufacture of the medical device. One is characterization of the size of aerosols produced by such means as Laser Light Scattering and Handerson Impactor instruments. Further, the beneficial effects of the inhalable products produced by the various embodiments of the invention are estimated and confirmed by such nuclear medicine procedures and blood oxygen estimations. The total fraction of drug available for inhalation in comparison to the inflow should not be less than 40%. The device may still function below this fraction but drug wastage may render the exercise costly or even uneconomic, particularly if the inhalable drug is costly. The following are non-limiting examples of the apparatus according to the present invention. Examples Example 1 A cubical food grade Perspex/plastic polymer container of 10-litre capacity was fitted with a plastic-body nebulizer whose inlet was fixed outside the body of the container. This inlet was connected to the air compressor with capacity of 12 litres/min. A hole was bored into the body to create the delivery end for connecting it to the outlet pipe pre-fitted with an air-filter. MMAD of the product passing through an appropriate spacer was 0.3 micron. A nuclear medicine Ventilation scan was done on a volunteer using conventional procedures where 300 microCi Tc-99m was inhaled as part of the product. It was compared to a standard nuclear medicine Ventilation scan. The distribution of radioactivity in respiratory tract confirmed deep penetration and preferred deposition of the aerosol in the lung. It also confirmed less than 15% drug wastage when used for more than 90 seconds. A Tc-99m MAA nuclear medicine perfusion scan was performed on appropriate individuals before and after treatment with the present invention to confirm increase in pulmonary circulation. Following such confirmations in the laboratory small clinical trials were done on patients using the product where most the advantageous as mentioned in another section were confirmed or clarified using appropriate instrumentation. As part of further quality control the same measures were carrying out on commercially available nebulizer assemblies meant for treating asthma. The tests confirmed the essential differences in stated parameters indicating that the current devices cannot function in place of the present invention. The present embodiment is reusable for many weeks/months after sufficient cleaning. Example 2 In another embodiment of the present invention a foldable polybag of food-grade material of 18-litre internal dimension was machined over a plastic nebulizer in such a way that a cut corner of the polybag was attached in an airtight fashion over the inlet of the nebulizer with its body inside the bag cavity. The opposite end of the polybag was machined over a food-grade plastic/metallic tube of 3-inches length and internal diameter of 1/2 inches. This plastic tube was either connected to an air filter of similar dimensions or itself constituted the inflow end of an air filter. A connecting tube attached the airflow filter either to the mouth-piece/air mask or to the outflow gas tube of the respirator in case of unconscious patients. This embodiment is meant to be disposed after a single or a few operations made with 24 hours. Following this time limit there is a risk of infection though there is no loss of utility. Drug wastage was less than 25% after the first 100 seconds. MMAD was 0.1 micron. The apparatus was able to increase blood oxygen level by 4-12% in different patients on 3-minute use upon nebulisation of commercially available salbutamol sulphate respiratory solution. We Claim: 1. A table-top drug-delivery apparatus for alveolar drug delivery which comprises an aerosol generator (10), a reservoir (13) having an inlet end (16) and an outlet end (17), a nebuliser (12) for containing medicament located at or connected to said reservoir (13) at said inlet end (16) thereof, said nebuliser (12) being connected to said aerosol generator (10), so that when the aerosol generator (10) is in an operative state, it causes said medicament in said nebuliser to be converted into fine droplets and deliver it to the inlet end (16) of said reservoir (13), a mouth piece (15) connected to said outlet end (17) of said reservoir (13) for receiving said fine droplets of the medicament, the inlet end (16) and outlet end (17) being so positioned that the time lag between receiving the nebulised medicament at the inlet end (16) and delivery thereof to said outlet end (17) is between 30 to 90 seconds so that fine droplets of said nebulised medicament of suitable for use as pulmonary dose are created and delivered to said mouth piece (17). 2. An apparatus as claimed in claim 1 wherein said time lag is about 45 seconds. 3. An apparatus as claimed in claim 1 or 2 wherein said nebuliser (12) is connected to said aerosol generator (10) by means of pre-connecting tubes (11). 4. An apparatus as claimed in any preceding claim wherein said reservoir (13) is of a metal or a polymer. 5. An apparatus as claimed in claim 5 wherein said polymer is a food-grade polymer. 6. An apparatus as claimed in any preceding claim wherein the capacity of the container is in the range of 1-50 litres. 7. An apparatus as claimed in claim 6 wherein said reservoir (13) has a volume in the range of 8-14 litres. 8. An apparatus as claimed in claim 1 wherein the working output of the external air compressor is in the range of 1-50 litres/min. 9. An apparatus as claimed in any preceding claim wherein said reservoir (13) has one or more further inlets receiving atmospheric or hot air. 10. An apparatus as claimed in any preceding claim wherein a gas mask or an oxygen source is connected between said outlet (17) and said mouth piece (15). 11. An apparatus as claimed in any preceding claim wherein said outlet end (17) is fitted with an air filter. 12. An apparatus as claimed in claim 1 wherein the outflow portal is fitted with a oneway air valve. 13. An apparatus as claimed in claim 1 wherein an air filter is connected between said outlet end (17) and mouth piece (15) said air filter having a maximum pore size of about 220 microns. 14. A table-top drug-delivery apparatus substantially as described hereinbefore and with reference to figure 2 of the accompanying drawings.

Full Text

Field of the Invention
The present invention relates to a table-top drug-delivery apparatus used for the prevention and management of primary and secondary forms of pulmonary hypertension, all conditions afflicting pulmonary microvasculature and pulmonary parenchyma.
Background of the Invention Pulmonary hypertension
Pulmonary hypertension can be primary (cause unknown) or secondary to a number of lung diseases. Primary pulmonary hypertension has no successful treatment and leads to mortality in the long run. Secondary pulmonary hypertension almost always complicates a number of diseases that lead to alveolar hypoxia. The present medical management appears inadequate to meet the challenge of this common and frequently a fatal or uncontrolled problem.
One of the main treatment modalities is systematically delivered vasodilators. Drugs like prazoin, nifedipine, phentolamine and sildenafin are among the variety of drugs tried for the purpose. The main problem with systematic delivery is that a high dosage in the circulation is required for the desired effect because the drug is distributed throughout the body fluids but beneficial effect is limited to the target organ-microvasculature of the lungs. The high dosage required in the blood limits the use of this treatment as use of such high dosages causes serious side effects like low blood pressure, significant palpitation and heart problems.
Further, this limits the duration of treatment only in severe cases and that also for few days or weeks only, while most of the diseases with which pulmonary hypertension is associated are chronic and mild in nature and may require treatment for years or even for life.
There may not be any benefit at all if regional blood supply is blocked significantly due to thrombosis in the lung microvasculature. Systematic vasodilators are therefore now considered an inadequate treatment in pulmonary hypertension but continue to be given in absence of a better treatment choice.
Other methods of treatment include oxygen inhalation (with or without 5% CO2), Nitric Oxide inhalation therapy, and compressed/ hyperbaric air administration. However, these therapies can only be given for short periods in time of emergency. Secondly, these are costly and mostly require infrastructural facilities for continuous administration. Thirdly, they almost immobilize the patient for the duration of the
therapy. Thus, though highly effective, these therapies are useful only as hospital-based treatment for a short period.
Inhalable aerosols of vasodilating substances have not been used for treating pulmonary hypertension clinically. The main cause of this has been the inability of the commercially available aerosol/nebulizer/dispersion systems to deliver pharmacological dose to the pulmonary level. These systems are basically designed to act at bronchi-trachea level and are not useful for managing pulmonary hypertension. Drugs acting locally in alveolar space
Apart from pulmonary hypertension, there are many other diseases that affect pulmonary tissue causing hypoxic hypoxemia and problem in oxygen transfer to blood. These include widespread infection (viral, bacterial or fungal), acute inflammations (diffuse bronchiolitis/alveolitis/ ARDS/allergic conditions) or chronic inflammations (all lung conditions leading to fibrotic changes), such as interstitial lung diseases and cancers. All these require higher concentration of drugs like antibiotics, antiviral substances, steroids, detergent/surfactants and anticancer drugs in the local space as compared to other tissues to enhance pharmacological effect and lower down side effects. For the same reasons as mentioned above systemic route and routine inhalation therapy is inadequate to meet the challenge though both continue to be used in absence of the better alternative. Systematically acting drugs routed through the lungs
Recently, delivery through buccal mucosa and lungs has been initiated for which higher deposition of the drug in the alveolar space is advantageous. Wider use or higher success rate has not been possible till now because alveoli are not automatically the preferred site of deposition of drugs inhaled though various commercially available methods and devices.
Considering the widespread nature of the disease (primary or secondary pulmonary hypertension), its fatal or incapacitating nature, and further considering the inadequacy of the present line of management with respect to control or cure, relief of symptoms, side effects, cost-effectiveness, patient comfort or availability, it is realized that a new treatment concept and methodology is urgently required. It is also realized that unconscious or highly breathless individuals may have some different requirements for inhalable drugs and routinely available methods and devices may not be sufficiently effective.
Objects of the Invention
It is therefore, an object of the present invention to provide a new drug-delivery system apparatus for treating or preventing primary or secondary pulmonary hypertension and any hypoxic hypoxemic states.
It is another object of the present invention to provide a drug-delivery apparatus for depositing a higher amount of drug in the alveolar space for better pharmacological action.
It is yet another object of the present invention to provide a drug-delivery apparatus that, upon combination with an air compressor and a nebulizer is capable of being used for prevention or treatment of the conditions as mentioned above, either independently or concurrently with other treatments, and can be used at home as well as hospital.
It is yet another object of the present invention to provide a drug-delivery apparatus that is capable of being for aerosolization of drugs using commercially available respirable solutions.
It is a further object of the present invention to provide a drug-delivery apparatus for treating pulmonary hypertension and hypoxic hypoxemia states that is reusable, lightweight, transportable, easily operable without much training and easy to dismantle and store.
It is yet another object of the present invention to provide a drug-delivery apparatus for treating pulmonary hypertension and hypoxic hypoxemia states that does not require a big infrastructure for operation and can be used in remote places. Summary of the invention
The above and other objects of the present invention are achieved by the apparatus of the present invention, which is based on the surprising finding that if the time lad between the formation of nebulised medicament and delivery thereof to the patient is maintained between 30 to 90 seconds, a perfect dosage suitable for pulmonary level is achieved.
Accordingly, the present invention provides a table-top drug-delivery apparatus for alveolar drug delivery which comprises an aerosol generator, a reservoir having an inlet end and an outlet end, a nebuliser for containing medicament located at or connected to said reservoir at said inlet end thereof, said nebuliser being connected to said aerosol generator, so that when the aerosol generator is in an operative state, it causes said medicament in said nebuliser to be converted into fine droplets and deliver
it to the inlet end of said reservoir, a mouth piece connected to said outlet end of said reservoir for receiving said fine droplets of the medicament, the inlet end and outlet end being so positioned that the time lag between receiving the nebulised medicament at the inlet end and delivery thereof to said outlet end is between 30 to 90 seconds so that fine droplets of said nebulised medicament of suitable for use as pulmonary dose are created and delivered to said mouth piece.
In a preferred feature, said time lag is about 45 seconds.
In a preferred feature, said nebuliser is connected to said aerosol generator by means of pre-connecting tubes.
In a preferred feature, said reservoir is of a metal or a polymer.
In a preferred feature, said polymer is a food-grade polymer.
In a preferred feature, the capacity of the container is in the range of 1-50 litres.
In a preferred feature, said reservoir has a volume in the range of 8-14 litres.
In a preferred feature, the working output of the external air compressor is in the range of 1-50 litres/min.
In a preferred feature, said reservoir has one or more further inlets receiving atmospheric or hot air.
In a preferred feature, a gas mask or an oxygen source is connected between said outlet and said mouth piece.
In a preferred feature, said outlet end is fitted with an air filter.
In a preferred feature, the outflow portal or the outlet end is fitted with an air valve, preferably, one-way air valve.
In a preferred feature, an air filter is are connected between said outlet end and mouth piece, said air filters having a maximum pore size of about 220 microns. Brief description of the accompanying Drawings
Figure 1 illustrates a conventional apparatus used for inhalation of drugs.
Figure 2 illustrates the novel drug-delivery apparatus according to the present invention. Description of the Invention
The present invention relates to a novel drug-delivery apparatus for the management (prevention and treatment) of primary and secondary hypertension. Thus, the present invention is also beneficial in a number of lung diseases that include chronic obstructive airway disease and its variants, bronchial asthma, diffuse tuberculosis, emphysema, interstitial lung diseases, Adult Respiratory Distress Syndrome and
pulmonary edema and various high altitude diseases associated with pulmonary hypertension. The present invention is also useful in the treatment of all conditions causing hypoxic hypoxemia. The mechanism of the apparatus is such that a majority of inhalable drug particles produced are significantly smaller than the preferred range presently available for treating asthma and asthma-like conditions.
Referring to Figure 1, the conventional system used for the purpose of inhalation of drugs comprises of an external air compressor (1) which is connected to an atomizer (3) by means of pre-connecting tubes (2) for creating fine droplets containing the medicament. The atomizer (3) is further connected to the mouthpiece (6) via post-connecting tubes (5) to facilitate inhalation of the medicament by he patient. During usage of this apparatus, the drug is atomized and then inhaled by the patient through the mouthpiece via the post-connecting tubes. The main disadvantage of the conventional inhaler is that the droplets created by the nebuliser and delivered to the patient are of such size that they are more suited for treatment of conditions at bronchi-tracheal level and are incapable of delivering dose to the pulmonary level. Therefore, such conventional apparatus is found to be extremely wanting for the management of pulmonary hypertension.
The present invention successfully addresses the problem associated with the prior art device. As shown in Figure 2, the device in accordance with the present invention comprises of a main body of the apparatus consists of a sealed container reservoir (13). The reservoir (13) is preferably of a volume ranging from 1-50 litres. In a preferred feature, the container (13) is capable of being compressed into a lesser volume for storage and transport purposes. The container may be metal or polymer-based and it is preferred that it is made from a flexible food grade polymer. The container (13) has an opening (not shown) that can be sealed on requirement and can be used for filling and servicing of the container (13). A standard nebulizer (12) is connected to or located inside said container (13) in an appropriately fixed position with the nebulizer's inflow portel (16) protruding out for connection to an external air compressor or power operated aerosol generator (10). The external air compressor or operated aerosol generator (10) preferably has a working output of 1-50 litres/min of hot or ambient temperature air. The nebulizer (12) preferably generates aerosols of size range 0.5-20 microns (MMAD). The container (13) has an outflow portal or delivery end (17) which is connected either to a fitting mouthpiece (15) or to a breathing mask or to oxygen carrying tubing, through post-connecting tubes and preferably through an
air-filter. The delivery end is preferably fitted with a one-way air valve (not shown) operating in this range of air flow. The inflow portal (16) and the delivery end (17) are spaced in a manner so that the time taken for flow of the drug from the inlet (16) to the delivery end (17) through the container is in the range of 30-90 seconds, preferably 45 seconds. This surprisingly and most unexpectedly achieves a pharmacological dose to the pulmonary level and is extremely useful for managing pulmonary hypertension. One or more holes are preferably bored into the body of the container that can be used to draw in hot air or atmospheric air using appropriate attachments.
The main body of the apparatus may be kept warm or hot by any other supportive apparatus. All the polymers used are preferably food grade polymers. To bring the drug-delivery apparatus to the functioning stage, the nebulizer (12) is filled with an appropriate drug solution and all the connections of the apparatus are hermetically sealed. Upon starting the air compressor or aerosol generator (10), the drug is released from the nebulizer (12) and the patient has to inhale it through the delivery end. The time lag between the inlet end (16) and delivery end (17) of the container (13) is in the range of 30 to 90 seconds which ensures that the size of the aerosols is efficacious for the treatment of pulmonary hypertension.. Exhalation may be performed into the delivery pipe or the atmosphere.
In accordance with the preferred embodiment of the present invention, the sequence and methodology of the manufacture process may be changed in a manner not detrimental to the stability and efficacy of the medical product.
An advantage of the present invention is higher local deposition and lower systemic dose. Thus the pharmacological effect is higher, systematic side effects are reduced and cost is reduced. Upon nebulization and inhalation, the nebulized drug is preferably delivered to the peripheral lung parenchyma, evading significant deposition in oropharynx, trachea, and stomach. These drugs include steroids, surfactants, antibiotics, antivirals, amongst others.
Further, the apparatus of the present invention is advantageous in conditions where inhalation route is followed for administering drugs having systematic action. These drugs include proteins, peptides and hormones amongst others. The apparatus can also be operated upon unconscious or semiconscious patients and those with severe dyspnoea and can be managed at home along with or without other support systems.
Certain quality control measures are embedded within the process of manufacture of the medical device. One is characterization of the size of aerosols
produced by such means as Laser Light Scattering and Handerson Impactor instruments. Further, the beneficial effects of the inhalable products produced by the various embodiments of the invention are estimated and confirmed by such nuclear medicine procedures and blood oxygen estimations. The total fraction of drug available for inhalation in comparison to the inflow should not be less than 40%. The device may still function below this fraction but drug wastage may render the exercise costly or even uneconomic, particularly if the inhalable drug is costly.
The following are non-limiting examples of the apparatus according to the present invention. Examples Example 1
A cubical food grade Perspex/plastic polymer container of 10-litre capacity was fitted with a plastic-body nebulizer whose inlet was fixed outside the body of the container. This inlet was connected to the air compressor with capacity of 12 litres/min. A hole was bored into the body to create the delivery end for connecting it to the outlet pipe pre-fitted with an air-filter.
MMAD of the product passing through an appropriate spacer was 0.3 micron. A nuclear medicine Ventilation scan was done on a volunteer using conventional procedures where 300 microCi Tc-99m was inhaled as part of the product. It was compared to a standard nuclear medicine Ventilation scan. The distribution of radioactivity in respiratory tract confirmed deep penetration and preferred deposition of the aerosol in the lung. It also confirmed less than 15% drug wastage when used for more than 90 seconds. A Tc-99m MAA nuclear medicine perfusion scan was performed on appropriate individuals before and after treatment with the present invention to confirm increase in pulmonary circulation. Following such confirmations in the laboratory small clinical trials were done on patients using the product where most the advantageous as mentioned in another section were confirmed or clarified using appropriate instrumentation.
As part of further quality control the same measures were carrying out on commercially available nebulizer assemblies meant for treating asthma. The tests confirmed the essential differences in stated parameters indicating that the current devices cannot function in place of the present invention.
The present embodiment is reusable for many weeks/months after sufficient cleaning.
Example 2
In another embodiment of the present invention a foldable polybag of food-grade material of 18-litre internal dimension was machined over a plastic nebulizer in such a way that a cut corner of the polybag was attached in an airtight fashion over the inlet of the nebulizer with its body inside the bag cavity. The opposite end of the polybag was machined over a food-grade plastic/metallic tube of 3-inches length and internal diameter of 1/2 inches. This plastic tube was either connected to an air filter of similar dimensions or itself constituted the inflow end of an air filter. A connecting tube attached the airflow filter either to the mouth-piece/air mask or to the outflow gas tube of the respirator in case of unconscious patients.
This embodiment is meant to be disposed after a single or a few operations made with 24 hours. Following this time limit there is a risk of infection though there is no loss of utility.
Drug wastage was less than 25% after the first 100 seconds. MMAD was 0.1 micron. The apparatus was able to increase blood oxygen level by 4-12% in different patients on 3-minute use upon nebulisation of commercially available salbutamol sulphate respiratory solution.

We Claim:
1. A table-top drug-delivery apparatus for alveolar drug delivery which comprises an aerosol generator (10), a reservoir (13) having an inlet end (16) and an outlet end (17), a nebuliser (12) for containing medicament located at or connected to said reservoir (13) at said inlet end (16) thereof, said nebuliser (12) being connected to said aerosol generator (10), so that when the aerosol generator (10) is in an operative state, it causes said medicament in said nebuliser to be converted into fine droplets and deliver it to the inlet end (16) of said reservoir (13), a mouth piece (15) connected to said outlet end (17) of said reservoir (13) for receiving said fine droplets of the medicament, the inlet end (16) and outlet end (17) being so positioned that the time lag between receiving the nebulised medicament at the inlet end (16) and delivery thereof to said outlet end (17) is between 30 to 90 seconds so that fine droplets of said nebulised medicament of suitable for use as pulmonary dose are created and delivered to said mouth piece (17).
2. An apparatus as claimed in claim 1 wherein said time lag is about 45 seconds.
3. An apparatus as claimed in claim 1 or 2 wherein said nebuliser (12) is connected to said aerosol generator (10) by means of pre-connecting tubes (11).
4. An apparatus as claimed in any preceding claim wherein said reservoir (13) is of a metal or a polymer.
5. An apparatus as claimed in claim 5 wherein said polymer is a food-grade polymer.
6. An apparatus as claimed in any preceding claim wherein the capacity of the container is in the range of 1-50 litres.
7. An apparatus as claimed in claim 6 wherein said reservoir (13) has a volume in the range of 8-14 litres.
8. An apparatus as claimed in claim 1 wherein the working output of the external air compressor is in the range of 1-50 litres/min.
9. An apparatus as claimed in any preceding claim wherein said reservoir (13) has one or more further inlets receiving atmospheric or hot air.
10. An apparatus as claimed in any preceding claim wherein a gas mask or an oxygen source is connected between said outlet (17) and said mouth piece (15).
11. An apparatus as claimed in any preceding claim wherein said outlet end (17) is fitted with an air filter.
12. An apparatus as claimed in claim 1 wherein the outflow portal is fitted with a oneway air valve.
13. An apparatus as claimed in claim 1 wherein an air filter is connected between said outlet end (17) and mouth piece (15) said air filter having a maximum pore size of about 220 microns.
14. A table-top drug-delivery apparatus substantially as described hereinbefore and with reference to figure 2 of the accompanying drawings.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=t0MBgzfz8WYswSfbzw+OUQ==&loc=+mN2fYxnTC4l0fUd8W4CAA==

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Patent Number

270901

Indian Patent Application Number

367/DEL/2005

PG Journal Number

05/2016

Publication Date

29-Jan-2016

Grant Date

27-Jan-2016

Date of Filing

21-Feb-2005

Name of Patentee

DIRECTOR GENERAL, DEFENCE RESEARCH & DEVELOPMENT ORGANISATION

Applicant Address

MINISTRY OF DEFENCE, GOVT OF INDIA, WEST BLOCK-VIII, WING 1, SEC-1, RK PURAM, NEW DELHI 110066

Inventors:

#	Inventor's Name	Inventor's Address
1	SUSHEEL CHANDRA	INMAS, LUCKNOW ROAD, DELHI-110 054
2	MAHINDER KUMAR CHOPRA	INMAS, LUCKNOW ROAD, DELHI-110 054
3	AJAY KUMAR SINGH	INMAS, LUCKNOW ROAD, DELHI-110 054
4	ASEEM BHATNAGAR	INMAS, LUCKNOW ROAD, DELHI-110 054

PCT International Classification Number

A61K9/00M20B; A61K9/14H6

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA