Title of Invention	A HAND-HELD DRUG DELIVERY APPARATUS FOR USE IN THE PREVENTION AND MANAGEMENT OF PRIMARY AND SECONDARY FORMS OF PULMONARY HYPERTENSION
Abstract	A hand-held drug delivery apparatus for use for the treatment of asthma and other pulmonary disorders such as pulmonary hypertension and hypotoxic hypoxemic conditions is disclosed. The apparatus comprises a nebuliser (1) for generating an aerosol of a medicament, a hollow tubing (2) connected to said nebuliser (1) for the passage of aerosol, an atomiser (3) connected to said hollow tubing (2) for converting said aerosol into microglobules containing said medicament, a reservoir (7) connected to said atomiser (3) for allowing said atomised microglobules containing said medicament a predetermined resident time for said microglobules to achieve a predetermined size and humidity and result in complete delivery of the medicine to peripheral lung parenchyma and avoid significant deposition in oropharynx, trachea and stomach, when inhaled by the patient, a mouth piece (4) connected between said atomiser (3) and reservoir (7) for facilitating inhalation of said microglobules containing said medicament by said patient, and a valve (6) for controlling the passage of said atomised microglobules into either the mouthpiece (4) or reservoir (7).

Title of Invention

A HAND-HELD DRUG DELIVERY APPARATUS FOR USE IN THE PREVENTION AND MANAGEMENT OF PRIMARY AND SECONDARY FORMS OF PULMONARY HYPERTENSION

Abstract

A hand-held drug delivery apparatus for use for the treatment of asthma and other pulmonary disorders such as pulmonary hypertension and hypotoxic hypoxemic conditions is disclosed. The apparatus comprises a nebuliser (1) for generating an aerosol of a medicament, a hollow tubing (2) connected to said nebuliser (1) for the passage of aerosol, an atomiser (3) connected to said hollow tubing (2) for converting said aerosol into microglobules containing said medicament, a reservoir (7) connected to said atomiser (3) for allowing said atomised microglobules containing said medicament a predetermined resident time for said microglobules to achieve a predetermined size and humidity and result in complete delivery of the medicine to peripheral lung parenchyma and avoid significant deposition in oropharynx, trachea and stomach, when inhaled by the patient, a mouth piece (4) connected between said atomiser (3) and reservoir (7) for facilitating inhalation of said microglobules containing said medicament by said patient, and a valve (6) for controlling the passage of said atomised microglobules into either the mouthpiece (4) or reservoir (7).

Full Text	Field of the invention The present invention relates to a hand-held drug-delivery apparatus for use in the prevention and management of primary and secondary forms of pulmonary hypertension and specifically of all conditions afflicting pulmonary micro-vasculature 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. The aim is to attempt to dilate the pulmonary blood vessels by giving the drug orally or by injection. Drugs like prazocin, 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 very high dosage required in the blood causes serious side effects like low blood pressure and significant palpitation and heart problems and limits the use of this treatment. 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 for the treatment of 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% C02), nitric oxide inhalation therapy, and compressed/hyperbaric air administration. However, these therapies can only be given for short periods and in times 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. Local acting particulate aerosols 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 effect pulmonary tissue. These include widespread infection (viral or 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 systematic route and routine inhalation therapy is inadequate to meet the challenge though both continue to be used in absence of the better alternative. The present invention is being introduced as the alternative. Systematically acting drugs routed through the lungs For fast action and to bypass GIT deactivation, or hepatic first-pass effect, intravenous or intramuscular injections are given. Recently, delivery through buccal mucosa and lungs has been initiated with success for which higher deposition of the drug in the alveolar space is advantageous. 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. Objects of the invention It is therefore, an object of the present invention to provide a hand-held drug delivery apparatus that can be used 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 that increases the deposition of the drug delivered in the pulmonary parenchyma thereby enhancing the local pharmacological effect. It is yet another object of the present invention to provide a drug delivery apparatus that can increase the oxygen transport to the blood from the alveolar space. It is still another object of the present invention to provide a drug delivery apparatus that can help in the management of a special type of secondary pulmonary hypertension that occurs at high altitude including high altitude hypoxic hypoxemia, acute and chronic mountain sickness and high altitude pulmonary edema. It is another object of the present invention to provide a drug delivery apparatus wherein significant drug deposition in oropharynx, trachea, and stomach is evaded. It is still another object of the present invention to provide a drug delivery apparatus wherein the drugs being delivered include steroids, surfactants, antibiotics, antivirals, etc. It is a further object of the present invention to provide a drug-delivery apparatus which can be used in conditions where inhalation route is followed for administering drugs having systematic action including proteins, peptides, hormones, etc. It is another object of the present invention to provide a drug delivery apparatus that is cost-effective, non-hazardous, capable of being used with minimal infrastructure needs and easy to utilise at field level. Summary of the invention The above and other objects of the present invention are achieved by the present invention which is based on the unexpected finding that if atomised microglubules containing medicament of predetermines size are delivered into the lungs, there is an increase in the deposition of the drug delivered in the pulmonary parenchyma thereby enhancing the local pharmacological effect. Accordingly, the present invention provides a hand-held drug delivery apparatus for use for the treatment of asthma and other pulmonary disorders such as pulmonary hypertension and hypotoxic hypoxemic conditions which comprises a nebuliser (1) for generating an aerosol of a medicament, a hollow tubing (2) connected to said nebuliser (1) for the passage of aerosol, an atomiser (3) connected to said hollow tubing (2) for converting said aerosol into microglobules containing said medicament, a reservoir (7) connected to said atomiser (3) for allowing said atomised microglobules containing said medicament a predetermined resident time for said microglobules to achieve a predetermined size and humidity and result in complete delivery of the medicine to peripheral lung parenchyma and avoid significant deposition in oropharynx, trachea and stomach, when inhaled by the patient, a mouth piece (4) connected between said atomiser (3) and reservoir (7) for facilitating inhalation of said microglobules containing said medicament by said patient, and a single or multidirectional valve (6) for controlling the passage of said atomised microglobules into either the mouthpiece (4) or reservoir (7). In a preferred feature, said valve is a bi-directional valve, which in first direction permits passage of said microglobules containing said medicament into the said mouth piece and in a second direction permits passage of said microglobules containing said medicament into said reservoir. In a preferred feature, wherein said valve is a bi-directional valve, which in a first direction permits passage of said microglobules containing said medicament into the said mouth piece from said atomiser and in a second direction permits passage of said microglobules containing said medicament into said mouth piece from said reservoir. In a preferred feature, said atomiser is connected to said mouth piece and reservoir by means of post connecting tubes. In a preferred feature, the tubes are made of a flexible metal or a polymer. In a preferred feature, the length of said hollow tubing is in the range of 10-1500 cm. In a preferred feature, the internal diameter of said hollow tubing is in the range of 0.5-10 cm. In a preferred feature, said nebuliser is connected to or is integral with an air compressor. In a preferred feature, the working output of the air compressor is in the range of 5-20 litres/min. In a preferred feature, the size of the particles generated by the nebulizer is in the range of 0.5-10 microns. In a preferred feature, the capacity of said reservoir is in the range of 4-20 litres. In a preferred feature, reservoir comprises a polymer bag. In a preferred feature, the delivery end is fitted with an air filter. In a preferred feature, any polymer used is food grade polymer. In a preferred feature, the polymer bag has a built-in air/humidity filter. In a preferred feature, an air/humidity filter is attached onto or into said valve In a preferred feature, an inlet is provided in the hollow tubing for intake of hot/atmospheric air. Brief description of the accompanying drawings Figure 1 illustrates the hand-held drug-delivery apparatus of the present invention. Figure 2 shows the standard nuclear medicine perfusion scans performed on individuals before and after treatment using the present invention. Detailed description of the invention The present invention relates to a hand-held drug-delivery apparatus used in the prevention and management of primary and secondary forms of pulmonary hypertension and specifically of all conditions afflicting pulmonary microvasculature and pulmonary parenchyma. It is also useful for drugs that need to be administered through lungs for systematic effects. Thus, this 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 will also benefit in all conditions causing hypoxic hypoxemia. The construction of the apparatus ensures that the preferred site of drug delivery is the alveolar region rather than gastric and oropharynx deposition seen with known commercial nebulizer systems that are used for treating asthma and asthama-like conditions. 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. As shown in figure 1, the main body of the apparatus comprises of a nebuliser for 1 connected to a hollow tube (2) which forms the main body f the apparatus. The hollow tube (2) is preferably made of either a flexible metal or a polymer, (polymer being more preferred). Th tube (2) is preferably 10-500 cm long, and has an internal diameter of about 0.5-10 cm. The nebuliser (1) is preferably a standard nebulizer and includes an air compressor. The nebuliser (1), also referred to as aerosol generator (1) are fitted at one end of the tube, called the entry end. The air compressor preferably produces a directed air volume of 5-20 litres/min of hot or ambient temperature air. The nebulizer (1) preferably generates aerosols of size range 0.5-10 microns. A hole is preferably bored into the body of the tube near its entry end that can be used to draw in hot air or atmospheric air. The other end, called the delivery end, is connected to a fitting mouthpiece (4) (preferably through an air-filter) either directly or through a T-Junction or a V-junction valve (6) made preferably of a polymer material. One end of the valve is connected to the delivery-end, and the other two ends are connected to a fitting mouthpiece (4) and a polymer bag (7) respectively. This bag is preferably of the dimension in the range of 4-20 litres and has preferably a built-in air/humidity filter or attached into or onto the body of T-junction/V-junction valve (6). The T-junction, or the V-junction preferably has a mechanical system whereby the flow of the aerosols can be directed either into the mouthpiece (4) or the polymer bag (7). 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 is filled with an appropriate drug solution and all the connections of the apparatus are hermetically sealed. Upon starting the air compressor (1), the drug is released from the nebulizer (1) and the patient has to inhale it through the delivery end. The patient has to inhale and exhale into the system for the required beneficial effect. Further the MMAD of the inhalable products produced by the various embodiments of the invention are estimated using Laser Scattering and Handerson Impactor instruments as a part of regular quality control embedded within the invention. 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. In accordance to 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. The following is a non-limiting example of the present invention: Example A 70-cm long PP tube (with internal diameter 2.5 cm) is connected to one end to the nebulizer-air compressor assembly and to the other end to an in-built T-junction made of PVP plastic. The T-junction in turn is connected to a polythene bag of 10 litres capacity through a air filter with mean pore size 800 microns. The third end of the T-junction is connected to a PP mouthpiece through an air filter with maximum pore size less than 200 micron. MMAD of the nebulized product generated from the system was 0,6-0.8 micron. A nuclear medicine Ventilation scan was done on a volunteer using conventional procedures where 300 micro Ci Tc-99m was inhaled as part of the product. It was compared to a standard nuclear medicine perfusion scan was performed on appropriate individuals before and after treatment with the present invention to confirm increase in pulmonary circulation (Figure 2). Following such confirmations in the laboratory large clinical trials were conducted at various sites where most the advantages as mentioned in another section were confirmed, including significant increase in blood oxygen. Comparison with commercial systems used for treating asthma showed that commercial systems were not able to perform as well as the apparatus of the present invention. We Claim: 1. A hand-held drug delivery apparatus for use for the treatment of asthma and other pulmonary disorders such as pulmonary hypertension and hypotoxic hypoxemic conditions which comprises a nebuliser (1) for generating an aerosol of a medicament, a hollow tubing (2) connected to said nebuliser (1) for the passage of aerosol, an atomiser (3) connected to said hollow tubing (2) for converting said aerosol into microglobules containing said medicament, a reservoir (7) connected to said atomiser (3) for allowing said atomised microglobules containing said medicament a predetermined resident time for said microglobules to achieve a predetermined size and humidity and result in complete delivery of the medicine to peripheral lung parenchyma and avoid significant deposition in oropharynx, trachea and stomach, when inhaled by the patient, a mouth piece (4) connected between said atomiser (3) and reservoir (7) for facilitating inhalation of said microglobules containing said medicament by said patient, and a valve (6) for controlling the passage of said atomised microglobules into either the mouthpiece (4) or reservoir (7). 2. An apparatus as claimed in claim 1 wherein said valve is a bi-directional valve, which in first direction permits passage of said microglobules containing said medicament into the said mouth piece and in a second direction permits passage of said microglobules containing said medicament into said reservoir. 3. An apparatus as claimed in claim 1 or 2 wherein said valve is a bi-directional valve, which in a first direction permits passage of said microglobules containing said medicament into the said mouth piece from said atomiser and in a second direction permits passage of said microglobules containing said medicament into said mouth piece from said reservoir. 4. An apparatus as claimed in any preceding claim wherein said atomiser is connected to said mouth piece and reservoir by means of post connecting tubes. 5. An apparatus as claimed in any preceding claim wherein the tubes are made of a flexible metal or a polymer. 6. An apparatus as claimed in claim 1 wherein the length of said hollow tubing is in the range of 10-1500 cm. 7. An apparatus as claimed in claim 1 wherein the internal diameter of said hollow tubing is in the range of 0.5-10 cm. 8. An apparatus as claimed in any preceding claim wherein said nebuliser is connected to or is integral with an air compressor. 9. An apparatus as claimed in claim 8 wherein the working output of the air compressor is in the range of 5-20 litres/min. 10. An apparatus as claimed in any preceding claim wherein the size of the particles generated by the nebulizer is in the range of 0.5-10 microns. 11. An apparatus as claimed in any preceding claim wherein the capacity of said reservoir is in the range of 4-20 litres. 12. An apparatus as claimed in any preceding claim wherein reservoir comprises a polymer bag. 13. An apparatus as claimed in any preceding claim wherein the delivery end is fitted with an air filter. 14. An apparatus as claimed in any preceding claim wherein any polymer used is food grade polymer. 15. An apparatus as claimed in claim 12 wherein the polymer bag has a built-in air/humidity filter. 16. An apparatus as claimed in any preceding claim wherein an air/humidity filter is attached onto or into said val 17. An apparatus as claimed in any preceding claim wherein an inlet is provided in the hollow tubing for intake of hot/atmospheric air. 18. A hand-held drug delivery apparatus substantially as described hereinbefore and with reference to the accompanying drawings.

Full Text

Field of the invention
The present invention relates to a hand-held drug-delivery apparatus for use in the prevention and management of primary and secondary forms of pulmonary hypertension and specifically of all conditions afflicting pulmonary micro-vasculature 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. The aim is to attempt to dilate the pulmonary blood vessels by giving the drug orally or by injection. Drugs like prazocin, 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 very high dosage required in the blood causes serious side effects like low blood pressure and significant palpitation and heart problems and limits the use of this treatment.
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 for the treatment of 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% C02), nitric oxide inhalation therapy, and compressed/hyperbaric air administration. However, these therapies can only be given for short periods and in times 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.
Local acting particulate aerosols 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 effect pulmonary tissue. These include widespread infection (viral or 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 systematic route and routine inhalation therapy is inadequate to meet the challenge though both continue to be used in absence of the better alternative. The present invention is being introduced as the alternative. Systematically acting drugs routed through the lungs
For fast action and to bypass GIT deactivation, or hepatic first-pass effect, intravenous or intramuscular injections are given. Recently, delivery through buccal mucosa and lungs has been initiated with success for which higher deposition of the drug in the alveolar space is advantageous.
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. Objects of the invention
It is therefore, an object of the present invention to provide a hand-held drug delivery apparatus that can be used 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
that increases the deposition of the drug delivered in the pulmonary parenchyma thereby enhancing the local pharmacological effect.
It is yet another object of the present invention to provide a drug delivery apparatus that can increase the oxygen transport to the blood from the alveolar space.
It is still another object of the present invention to provide a drug delivery apparatus that can help in the management of a special type of secondary pulmonary hypertension that occurs at high altitude including high altitude hypoxic hypoxemia, acute and chronic mountain sickness and high altitude pulmonary edema.
It is another object of the present invention to provide a drug delivery apparatus wherein significant drug deposition in oropharynx, trachea, and stomach is evaded.
It is still another object of the present invention to provide a drug delivery apparatus wherein the drugs being delivered include steroids, surfactants, antibiotics, antivirals, etc.
It is a further object of the present invention to provide a drug-delivery apparatus which can be used in conditions where inhalation route is followed for administering drugs having systematic action including proteins, peptides, hormones, etc.
It is another object of the present invention to provide a drug delivery apparatus that is cost-effective, non-hazardous, capable of being used with minimal infrastructure needs and easy to utilise at field level. Summary of the invention
The above and other objects of the present invention are achieved by the present invention which is based on the unexpected finding that if atomised microglubules containing medicament of predetermines size are delivered into the lungs, there is an increase in the deposition of the drug delivered in the pulmonary parenchyma thereby enhancing the local pharmacological effect.
Accordingly, the present invention provides a hand-held drug delivery apparatus for use for the treatment of asthma and other pulmonary disorders such as pulmonary hypertension and hypotoxic hypoxemic conditions which comprises a nebuliser (1) for generating an aerosol of a medicament, a hollow tubing (2) connected to said nebuliser (1) for the passage of aerosol, an atomiser (3) connected to said hollow tubing (2) for converting said aerosol into microglobules containing said medicament, a reservoir (7) connected to said atomiser (3) for allowing said atomised microglobules containing said medicament a predetermined resident time for said microglobules to achieve a predetermined size and humidity and result in complete delivery of the medicine to
peripheral lung parenchyma and avoid significant deposition in oropharynx, trachea and stomach, when inhaled by the patient, a mouth piece (4) connected between said atomiser (3) and reservoir (7) for facilitating inhalation of said microglobules containing said medicament by said patient, and a single or multidirectional valve (6) for controlling the passage of said atomised microglobules into either the mouthpiece (4) or reservoir (7).
In a preferred feature, said valve is a bi-directional valve, which in first direction permits passage of said microglobules containing said medicament into the said mouth piece and in a second direction permits passage of said microglobules containing said medicament into said reservoir.
In a preferred feature, wherein said valve is a bi-directional valve, which in a first direction permits passage of said microglobules containing said medicament into the said mouth piece from said atomiser and in a second direction permits passage of said microglobules containing said medicament into said mouth piece from said reservoir.
In a preferred feature, said atomiser is connected to said mouth piece and reservoir by means of post connecting tubes.
In a preferred feature, the tubes are made of a flexible metal or a polymer.
In a preferred feature, the length of said hollow tubing is in the range of 10-1500 cm.
In a preferred feature, the internal diameter of said hollow tubing is in the range of 0.5-10 cm.
In a preferred feature, said nebuliser is connected to or is integral with an air compressor.
In a preferred feature, the working output of the air compressor is in the range of 5-20 litres/min.
In a preferred feature, the size of the particles generated by the nebulizer is in the range of 0.5-10 microns.
In a preferred feature, the capacity of said reservoir is in the range of 4-20 litres.
In a preferred feature, reservoir comprises a polymer bag.
In a preferred feature, the delivery end is fitted with an air filter.
In a preferred feature, any polymer used is food grade polymer.
In a preferred feature, the polymer bag has a built-in air/humidity filter.
In a preferred feature, an air/humidity filter is attached onto or into said valve
In a preferred feature, an inlet is provided in the hollow tubing for intake of
hot/atmospheric air.
Brief description of the accompanying drawings
Figure 1 illustrates the hand-held drug-delivery apparatus of the present invention.
Figure 2 shows the standard nuclear medicine perfusion scans performed on individuals before and after treatment using the present invention. Detailed description of the invention
The present invention relates to a hand-held drug-delivery apparatus used in the prevention and management of primary and secondary forms of pulmonary hypertension and specifically of all conditions afflicting pulmonary microvasculature and pulmonary parenchyma. It is also useful for drugs that need to be administered through lungs for systematic effects. Thus, this 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 will also benefit in all conditions causing hypoxic hypoxemia. The construction of the apparatus ensures that the preferred site of drug delivery is the alveolar region rather than gastric and oropharynx deposition seen with known commercial nebulizer systems that are used for treating asthma and asthama-like conditions. 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.
As shown in figure 1, the main body of the apparatus comprises of a nebuliser for 1 connected to a hollow tube (2) which forms the main body f the apparatus. The hollow tube (2) is preferably made of either a flexible metal or a polymer, (polymer being more preferred). Th tube (2) is preferably 10-500 cm long, and has an internal diameter of about 0.5-10 cm. The nebuliser (1) is preferably a standard nebulizer and includes an air compressor. The nebuliser (1), also referred to as aerosol generator (1) are fitted at one end of the tube, called the entry end. The air compressor preferably produces a directed air volume of 5-20 litres/min of hot or ambient temperature air. The nebulizer (1) preferably generates aerosols of size range 0.5-10 microns. A hole is preferably bored into the body of the tube near its entry end that can be used to draw in hot air or atmospheric air. The other end, called the delivery end, is connected to a fitting mouthpiece (4) (preferably through an air-filter) either directly or through a T-Junction or a V-junction valve (6) made preferably of a polymer material. One end of the valve is connected to the delivery-end, and the other two ends are connected to a fitting mouthpiece (4) and a polymer bag (7)
respectively. This bag is preferably of the dimension in the range of 4-20 litres and has preferably a built-in air/humidity filter or attached into or onto the body of T-junction/V-junction valve (6). The T-junction, or the V-junction preferably has a mechanical system whereby the flow of the aerosols can be directed either into the mouthpiece (4) or the polymer bag (7).
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 is filled with an appropriate drug solution and all the connections of the apparatus are hermetically sealed. Upon starting the air compressor (1), the drug is released from the nebulizer (1) and the patient has to inhale it through the delivery end. The patient has to inhale and exhale into the system for the required beneficial effect.
Further the MMAD of the inhalable products produced by the various embodiments of the invention are estimated using Laser Scattering and Handerson Impactor instruments as a part of regular quality control embedded within the invention. 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.
In accordance to 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.
The following is a non-limiting example of the present invention: Example
A 70-cm long PP tube (with internal diameter 2.5 cm) is connected to one end to the nebulizer-air compressor assembly and to the other end to an in-built T-junction made of PVP plastic. The T-junction in turn is connected to a polythene bag of 10 litres capacity through a air filter with mean pore size 800 microns. The third end of the T-junction is connected to a PP mouthpiece through an air filter with maximum pore size less than 200 micron.
MMAD of the nebulized product generated from the system was 0,6-0.8 micron. A nuclear medicine Ventilation scan was done on a volunteer using conventional procedures where 300 micro Ci Tc-99m was inhaled as part of the product. It was compared to a standard nuclear medicine perfusion scan was performed on appropriate individuals before and after treatment with the present invention to confirm increase in pulmonary circulation
(Figure 2). Following such confirmations in the laboratory large clinical trials were conducted at various sites where most the advantages as mentioned in another section were confirmed, including significant increase in blood oxygen. Comparison with commercial systems used for treating asthma showed that commercial systems were not able to perform as well as the apparatus of the present invention.

We Claim:
1. A hand-held drug delivery apparatus for use for the treatment of asthma and other pulmonary disorders such as pulmonary hypertension and hypotoxic hypoxemic conditions which comprises a nebuliser (1) for generating an aerosol of a medicament, a hollow tubing (2) connected to said nebuliser (1) for the passage of aerosol, an atomiser (3) connected to said hollow tubing (2) for converting said aerosol into microglobules containing said medicament, a reservoir (7) connected to said atomiser (3) for allowing said atomised microglobules containing said medicament a predetermined resident time for said microglobules to achieve a predetermined size and humidity and result in complete delivery of the medicine to peripheral lung parenchyma and avoid significant deposition in oropharynx, trachea and stomach, when inhaled by the patient, a mouth piece (4) connected between said atomiser (3) and reservoir (7) for facilitating inhalation of said microglobules containing said medicament by said patient, and a valve (6) for controlling the passage of said atomised microglobules into either the mouthpiece (4) or reservoir (7).
2. An apparatus as claimed in claim 1 wherein said valve is a bi-directional valve, which in first direction permits passage of said microglobules containing said medicament into the said mouth piece and in a second direction permits passage of said microglobules containing said medicament into said reservoir.
3. An apparatus as claimed in claim 1 or 2 wherein said valve is a bi-directional valve, which in a first direction permits passage of said microglobules containing said medicament into the said mouth piece from said atomiser and in a second direction permits passage of said microglobules containing said medicament into said mouth piece from said reservoir.
4. An apparatus as claimed in any preceding claim wherein said atomiser is connected to said mouth piece and reservoir by means of post connecting tubes.
5. An apparatus as claimed in any preceding claim wherein the tubes are made of a flexible metal or a polymer.
6. An apparatus as claimed in claim 1 wherein the length of said hollow tubing is in the range of 10-1500 cm.
7. An apparatus as claimed in claim 1 wherein the internal diameter of said hollow
tubing is in the range of 0.5-10 cm.
8. An apparatus as claimed in any preceding claim wherein said nebuliser is connected to or is integral with an air compressor.
9. An apparatus as claimed in claim 8 wherein the working output of the air compressor is in the range of 5-20 litres/min.
10. An apparatus as claimed in any preceding claim wherein the size of the particles generated by the nebulizer is in the range of 0.5-10 microns.
11. An apparatus as claimed in any preceding claim wherein the capacity of said reservoir is in the range of 4-20 litres.
12. An apparatus as claimed in any preceding claim wherein reservoir comprises a polymer bag.
13. An apparatus as claimed in any preceding claim wherein the delivery end is fitted with an air filter.
14. An apparatus as claimed in any preceding claim wherein any polymer used is food grade polymer.
15. An apparatus as claimed in claim 12 wherein the polymer bag has a built-in air/humidity filter.
16. An apparatus as claimed in any preceding claim wherein an air/humidity filter is attached onto or into said val
17. An apparatus as claimed in any preceding claim wherein an inlet is provided in the hollow tubing for intake of hot/atmospheric air.
18. A hand-held drug delivery apparatus substantially as described hereinbefore and with reference to the accompanying drawings.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=TO5xA3eMOyIvQ/DVePQfvw==&loc=+mN2fYxnTC4l0fUd8W4CAA==

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Patent Number

270274

Indian Patent Application Number

366/DEL/2005

PG Journal Number

50/2015

Publication Date

11-Dec-2015

Grant Date

08-Dec-2015

Date of Filing

21-Feb-2005

Name of Patentee

THE DIRECTOR GENERAL, DEFENCE RESEARCH AND 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	ASEEM BHATNAGAR	INMAS, LUCKNOW ROAD, DELHI-110 054
2	VIJAY PADMAN	C/O 56, APO,LEH,PIN-901205
3	ANUPAM MONDAL	INMAS, LUCKNOW ROAD, DELHI-110 054
4	AJAY KUMAR SINGH	INMAS, LUCKNOW ROAD, DELHI-110 054
5	MAHINDER KUMAR CHOPRA	INMAS, LUCKNOW ROAD, DELHI-110 054
6	SUSHEEL CHANDRA	INMAS, LUCKNOW ROAD, DELHI-110 054
7	RAVI KASHYAP	INMAS, LUCKNOW ROAD, DELHI-110 054
8	TURGA RAVINDRANATH	INMAS, LUCKNOW ROAD, DELHI-110 054

PCT International Classification Number

A61K31/00; A61P11/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA