CA2382567A1 - Use of at least one substance based on nicotine and/or a substance produced from said one substance for the manufacture of a medicament, and a method for treatment of obstructive lung disease - Google Patents
Use of at least one substance based on nicotine and/or a substance produced from said one substance for the manufacture of a medicament, and a method for treatment of obstructive lung disease Download PDFInfo
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- CA2382567A1 CA2382567A1 CA002382567A CA2382567A CA2382567A1 CA 2382567 A1 CA2382567 A1 CA 2382567A1 CA 002382567 A CA002382567 A CA 002382567A CA 2382567 A CA2382567 A CA 2382567A CA 2382567 A1 CA2382567 A1 CA 2382567A1
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- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 title claims abstract description 54
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 229960002715 nicotine Drugs 0.000 title claims abstract description 49
- 239000000126 substance Substances 0.000 title claims abstract description 38
- 239000003814 drug Substances 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 15
- 208000011623 Obstructive Lung disease Diseases 0.000 title claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 6
- 206010014561 Emphysema Diseases 0.000 claims abstract description 13
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 9
- 241001465754 Metazoa Species 0.000 claims abstract description 8
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 8
- 239000008280 blood Substances 0.000 claims abstract description 7
- 210000004369 blood Anatomy 0.000 claims abstract description 7
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 5
- 230000002146 bilateral effect Effects 0.000 claims description 9
- 239000011230 binding agent Substances 0.000 claims description 6
- 206010010356 Congenital anomaly Diseases 0.000 claims description 5
- 239000007857 degradation product Substances 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 description 26
- 210000000621 bronchi Anatomy 0.000 description 14
- 210000002345 respiratory system Anatomy 0.000 description 14
- 230000000391 smoking effect Effects 0.000 description 14
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 230000006378 damage Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 201000003144 pneumothorax Diseases 0.000 description 8
- 206010061688 Barotrauma Diseases 0.000 description 7
- 230000002685 pulmonary effect Effects 0.000 description 7
- 239000003570 air Substances 0.000 description 6
- 210000004400 mucous membrane Anatomy 0.000 description 4
- 230000029058 respiratory gaseous exchange Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 210000004224 pleura Anatomy 0.000 description 3
- 230000008092 positive effect Effects 0.000 description 3
- 230000005586 smoking cessation Effects 0.000 description 3
- 239000007910 chewable tablet Substances 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000002633 protecting effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 239000000779 smoke Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 208000003898 Mediastinal Emphysema Diseases 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 206010050184 Pneumomediastinum Diseases 0.000 description 1
- 206010048731 Pneumopericardium Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- 239000012080 ambient air Substances 0.000 description 1
- 208000002352 blister Diseases 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 201000000260 interstitial emphysema Diseases 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- -1 nicotine compound Chemical class 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000004796 pathophysiological change Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 210000003456 pulmonary alveoli Anatomy 0.000 description 1
- 230000005801 respiratory difficulty Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/465—Nicotine; Derivatives thereof
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention refers to a use of at least one substance based on nicotine and/or a substance produced from said one substance for the manufacture of a medicament to be supplied to an individual of a human being or an animal for the purpose of counteracting, in a prophylactic or therapeutic manner, obstructive lung diseases, in particular pulmonary emphysema. The medicament is intended to be supplied via the blood path and to be administered via the gastrointestinal tract, transdermally, intravascularly, intranasally or intravaginally. The invention also refers to a method for prophylactic or therapeutic treatment of obstructive lung diseases of an individual of a human being or an animal, wherein said individual is supplied with a nicotine-based substance.
Description
Use of at least one substance based on nicotine andlor a substance produced from said one substance for the manufacture of a medicament, and a method for treatment of obstructive lung diseases THE BACKGROUND OF THE INVENTION AND PRIOR ART
The present invention refers to a use of at least one substance based on nicotine andlor a substance produced from said one substance for the manufacture of a medicament to be supplied to an individual of a human being or an animal. The invention also refers to a method for prophylactic or therapeutic treatment of obstructive lung diseases of in individual of a human being or an animal.
Pulmonary emphysema is a common disease, which in particular affects smokers. The disease is characterised by a permanent expansion and destruction of the finest bronchi and the walls of the alveoli. Pulmonary emphysema is a very serious disease and the destruction process is irreversible so that the disease leads to increasing respiratory difficulties.
Pulmonary emphysema belongs to a group of diseases usually called obstructive lung diseases due to the fact that the disease obstructs the flow in the respiratory tracts. The obstruction is the underlying cause also to pulmonary barotrauma, including spontaneous pneumothorax. These diseases have symptoms and localised effects to the lung tissue similar to pulmonary emphysema.
During normal inhalation the bronchi are expanded, which counteracts the obstruction to a certain extent. During the following exhalation the lung tissue is compressed, including the bronchi, and wo oms6s~ pcris~ooroi6a3 a somewhat smaller gas volume may therefore flow through the respiratory tract. This leads to a valve effect when a certain balance arises. By a certain overpressure in the respiratory tracts and the lung, the obstruction may be overcome and the inhaled gas volume be emptied. The pressure in the lung is however not sufficient for completely emptying the lung. There is always a certain amount of air (residual volume; normally about 500 ml of an adult) in the lung after the first breath. This balance depends inter alia on and is influenced by the ambient air pressure; the more the weaker the respiratory tracts, especially for early born, immature children.
During smoking the mucous membrane in the respiratory tracts and bronchi is irritated, which leads to a swelling of the mucous membrane. This swelling decreases the lumen of the respiratory tracts, i.e. the obstruction arises and thus the air flow in the respiratory tracts is restrained. This leads to an increase of the so-called valve effect, to a higher pressure in the respiratory tracts and the lung, and to a larger residual volume in the lung. The increase also leads to a destruction of tissue, which further reduces the gas exchange, i.e. the breathing capacity. If nicotine or nicotine-like substances are supplied, not via the respiration, a vessel contracting, decongestant effect, which reduces the obstruction, is obtained.
Pulmonary barotrauma appears due to such a tissue destruction by the inner pressure. Pulmonary barotrauma may principally refer to one single alveolus or a smallest respiratory tract, or several small alveoli within the lung. If this tissue destruction process is expanded to the whole lung it is called pulmonary emphysema. In the cases when air is collected diffusely in the lung tissue proper, we have an interstitial emphysema or in a delimited way, a bulls (blister). If the air is collected adjacent to the pleura in a delimited manner we have a subpleural bleb. The air may also come to the intrapulmonary space and we have a so-called pneumomediastinum or into the heart sack; pneumopericardium. If the tissue destruction is expanded so that the pleura is destroyed, we have a spontaneous pneumothorax (SP). With regard to the fact that pathophysiological changes in the lung are documented in case of SP, it is not any longer relevant to call SP a disease of the pleura.
The obstruction leads to an expansion in a lung part and thus to a compression of the surrounding lung part. Such an expansion and compression is irreversible for a smoker even if he would stop smoking. If the surrounding compressed lung part is very large, surgery could be considered for removing a large significant blister and thus create space for the respiratory work. However, it is very rare that a patient is suitable for such an operation, whereby an expected effect is far from being optimal.
The destruction of tissue may be localised to the upper part of the lung, due to bronchial anomaly at spontaneous pneumothorax or to the lower part of the lung at alfa-1-antitrypsin AAT-deficiency. AAT
is an enzyme protecting the elastic fibres of the lung. The fibres are subjected to the largest load in the lower part, where the largest expansion of the lung takes place when we breathe. if the protecting effect ceases, the elasticity is lost and this can be easily seen on the most stressed tissue part.
The destruction may also be general without anomaly or AAT-deficiency due to smoking.
Bilateral bronchial anomaly is an anatomical congenital obstruction with a characteristically changed branching structure of the respiratory tracts and this obstruction may be increased by smoking. Bilateral bronchial anomaly may today be shown by diagnostic methods known per se, for instance by means of X-ray pictures disclosing the bronchial structure of a patient. The respiratory tracts consist of bronchi, which from the main bronchus are divided to smaller and smaller bronchi. The first bronchus forms the bronchus of the first generation, the bronchi after the first division are called the bronchi of the second generation, after the second division the bronchi of the third generation, etc. Bilateral bronchial anomaly means that the bronchi of the third generation are missing in an individual and are replaced by very characteristic, WO 01/15697 PC'IYSEOOI01683 irregular narrowing connections. The air exchange to and especially from the alveoli will thus be hampered by this defect bronchial structure, which is identifiable.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a means, which counteracts such obstructive lung diseases in a prophylactic or therapeutic manner.
This object is obtained by the use of at least one substance based on nicotine and/or a substance produced from said one substance for the manufacture of a medicament to be supplied to an individual of a human being or an animal for the purpose of counteracting obstructive lung diseases in a prophylactic or therapeutic manner.
The applicant has realised that nicotine, if it is not supplied via the respiration, has an inhibitory effect on the development of respiratory tract obstruction followed by the irreversible substance loss, elasticity loss and expansion of the lung tissue, i.e. the negative effects arising from pulmonary emphysema, pulmonary barotrauma and spontaneous pneumothorax. By supplying nicotine to the body of the persons suffering by pulmonary emphysema, it is thus possible to prevent or delimit the development of the disease.
Nicotine also ought to have a prophylactic effect, i.e. the origin of pulmonary emphysema of persons having a risk to be effected by this disease, for instance smokers, which have stopped smoking, may be prevented by the supply of nicotine, however not via the bronchi, respiratory organs.
The definition at least one substance based on nicotine andlor a substance produced from said one substance is to be given a broad interpretation and in this definitian are included substantially pure nicotine, nicotine compounds, nicotine related compounds, nicotine derivatives, intermediate metabalites of nicotine and/or nicotine compounds, degradation products from nicotine or nicotine compounds with completely or partly identical, similar effects.
WO 01!15697 PCT/SE00/01683 Nicotine acts via nicotine receptors partly in the vegetative system and partly in the muscles. The nicotine has firstly an irritating (vasoconstrictive) effect on the blood vessels. The vasoconstriction 5 leads to a decongestion of the mucous membrane in the respiratory tracts, which counteracts the obstruction. If nicotine is supplied in significantly higher doses than intended by the present invention, a paralysis (vessel relaxion) arises via the vegetative ganglions and the central nervous system.
According to an embodiment of the invention, the nicotine is to be supplied via the blood. It is essential that the nicotine reaches the lungs via the blood and not via the respiration. The positive effect of nicotine to the disease pulmonary emphysema can thus not be obtained if nicotine is supplied via tobacco smoke. However, it is not excluded that nicotine has a positive effect if it is supplied to the blood immediately at the same time as the patient is smoking even if the positive effect in this case will be reduced.
According to a further embodiment of the invention, the nicotine may be administered via the gastrointestinal tract, transdermally, intravascularly, intranasally or intravaginally. The nicotine may thus be supplied in various manners except via the respiratory tracts and the lungs. For instance, the nicotine may be supplied by means of plasters, spray, suppository, pills to be swallowed or in the form of chewable tablets or oral tablets, which are known in connection with smoking cessation. According to a further example, the nicotine may be administered by means of inhalation in such a way that most of the nicotine is taken up by the mucous membranes in the mouth (gastrointestinal tract).
According to a further embodiment of the invention, said substance based on nicotine and/or substances produced by said one substance are absorbed in a binding agent. Such a binding agent may permit a slow administration of the active nicotine substance, so-called "slow release".
WV Ul/1~0Y7 YC:~1~/J1GUU/U10~
According to a further embodiment of the invention, the use is intended for said individual, which has a congenital bilateral bronchial anomaly. As mentioned initially, the destruction of the lung tissue, due to smoking, may be general without anomaly or due to AAT-deficiency. The applicant has however realised that the risk of serious obstructions in the lungs, which leads to pulmonary barotrauma, such as spontaneous pneumothorax and pulmonary emphysema, is substantially higher for smokers having a congenital bilateral bronchial anomaly than for smokers not having such an anomaly. This risk ought to be in the order of 2000-3000 % higher for smokers with, than smokers without bilateral bronchial anomaly.
The formed structure of a bilateral bronchial anomaly is associated with a different function, such as ventilation, perfusion, and a high sensibility for external factors, such as smoking.
The object is also obtained by a method for prophylactic or therapeutic treatment of obstructive lung diseases of an individual of a human being or an animal, wherein said individual is supplied with a nicotine-based substance.
DESCRIPTION OF EMBODIMENTS OF THE INVENTION
Investigations have been made showing an inverted correlation between smoking habits of pregnant women and the risk of pulmonary barotrauma of the new-born children of the women.
Thus, new-born children of smoking women have a lower predisposition to get pulmonary barotrauma than new-born children of women which are not smoking. Investigations also show that foetuses of women which smoke have nicotine in the blood. This inverted relation thus indicates that nicotine may counteract obstructive lung diseases.
It is known to use nicotine, i.e. 3-(1-metyl-2-pyrrolidyl) pyridine for smoking cessation, i.e. for reducing the abstinence complaints. The use now proposed according to the present invention may thus be regarded as a second medical indication. The medical effect mentioned above may be obtained for smokers which are smoking, '7 smokers which are giving up their smoking, smokers which have giving up their smoking until this disease risk is reduced, individuals with a lung obstruction and when one wishes to reduce the obstruction in remaining parts of the lungs andlor no other treatment is available.
It is of course important that the quantity of nicotine supplied is adapted to the individual to receive the medicament. A suitable dosing for obtaining the desired effect may be 1-100 mgl24h, preferably 5-50 mgl24h, for instance 7mg/24h, 14mg/24h or 21 mg/24h. These doses refer to a medicament with nicotine in substantially pure form.
Such a dose may for instance be obtained by means of tablets of the type called "slow release". Such tablets may contain a binding agent permitting a slow release of the active nicotine substance.
The tablets are suitably designed in such a way that the patient may take one or two tablets per 24h. The dose may also be obtained by the plasters mentioned above or chewable tablets which also may contain flavouring substances, consistency agents and/or any binding agent having an ability to bind nicotine and permit the release thereof at a suitable speed. The nicotine may be present in a substantially free form in such a binding agent, be chemically bounded to any substance or any nicotine compound or as a nicotine derivative.
In contrast to the medicament for smoking cessation, there is no desire of the present invention to obtain any quick addition when the patient suffers from abstinence but rather a slow and over the time uniform dosing speed in order to obtain an equal plasma concentration and bioavailability.
The invention is not limited to the examples given but may be varied and modified within the scope of the following claims.
The present invention refers to a use of at least one substance based on nicotine andlor a substance produced from said one substance for the manufacture of a medicament to be supplied to an individual of a human being or an animal. The invention also refers to a method for prophylactic or therapeutic treatment of obstructive lung diseases of in individual of a human being or an animal.
Pulmonary emphysema is a common disease, which in particular affects smokers. The disease is characterised by a permanent expansion and destruction of the finest bronchi and the walls of the alveoli. Pulmonary emphysema is a very serious disease and the destruction process is irreversible so that the disease leads to increasing respiratory difficulties.
Pulmonary emphysema belongs to a group of diseases usually called obstructive lung diseases due to the fact that the disease obstructs the flow in the respiratory tracts. The obstruction is the underlying cause also to pulmonary barotrauma, including spontaneous pneumothorax. These diseases have symptoms and localised effects to the lung tissue similar to pulmonary emphysema.
During normal inhalation the bronchi are expanded, which counteracts the obstruction to a certain extent. During the following exhalation the lung tissue is compressed, including the bronchi, and wo oms6s~ pcris~ooroi6a3 a somewhat smaller gas volume may therefore flow through the respiratory tract. This leads to a valve effect when a certain balance arises. By a certain overpressure in the respiratory tracts and the lung, the obstruction may be overcome and the inhaled gas volume be emptied. The pressure in the lung is however not sufficient for completely emptying the lung. There is always a certain amount of air (residual volume; normally about 500 ml of an adult) in the lung after the first breath. This balance depends inter alia on and is influenced by the ambient air pressure; the more the weaker the respiratory tracts, especially for early born, immature children.
During smoking the mucous membrane in the respiratory tracts and bronchi is irritated, which leads to a swelling of the mucous membrane. This swelling decreases the lumen of the respiratory tracts, i.e. the obstruction arises and thus the air flow in the respiratory tracts is restrained. This leads to an increase of the so-called valve effect, to a higher pressure in the respiratory tracts and the lung, and to a larger residual volume in the lung. The increase also leads to a destruction of tissue, which further reduces the gas exchange, i.e. the breathing capacity. If nicotine or nicotine-like substances are supplied, not via the respiration, a vessel contracting, decongestant effect, which reduces the obstruction, is obtained.
Pulmonary barotrauma appears due to such a tissue destruction by the inner pressure. Pulmonary barotrauma may principally refer to one single alveolus or a smallest respiratory tract, or several small alveoli within the lung. If this tissue destruction process is expanded to the whole lung it is called pulmonary emphysema. In the cases when air is collected diffusely in the lung tissue proper, we have an interstitial emphysema or in a delimited way, a bulls (blister). If the air is collected adjacent to the pleura in a delimited manner we have a subpleural bleb. The air may also come to the intrapulmonary space and we have a so-called pneumomediastinum or into the heart sack; pneumopericardium. If the tissue destruction is expanded so that the pleura is destroyed, we have a spontaneous pneumothorax (SP). With regard to the fact that pathophysiological changes in the lung are documented in case of SP, it is not any longer relevant to call SP a disease of the pleura.
The obstruction leads to an expansion in a lung part and thus to a compression of the surrounding lung part. Such an expansion and compression is irreversible for a smoker even if he would stop smoking. If the surrounding compressed lung part is very large, surgery could be considered for removing a large significant blister and thus create space for the respiratory work. However, it is very rare that a patient is suitable for such an operation, whereby an expected effect is far from being optimal.
The destruction of tissue may be localised to the upper part of the lung, due to bronchial anomaly at spontaneous pneumothorax or to the lower part of the lung at alfa-1-antitrypsin AAT-deficiency. AAT
is an enzyme protecting the elastic fibres of the lung. The fibres are subjected to the largest load in the lower part, where the largest expansion of the lung takes place when we breathe. if the protecting effect ceases, the elasticity is lost and this can be easily seen on the most stressed tissue part.
The destruction may also be general without anomaly or AAT-deficiency due to smoking.
Bilateral bronchial anomaly is an anatomical congenital obstruction with a characteristically changed branching structure of the respiratory tracts and this obstruction may be increased by smoking. Bilateral bronchial anomaly may today be shown by diagnostic methods known per se, for instance by means of X-ray pictures disclosing the bronchial structure of a patient. The respiratory tracts consist of bronchi, which from the main bronchus are divided to smaller and smaller bronchi. The first bronchus forms the bronchus of the first generation, the bronchi after the first division are called the bronchi of the second generation, after the second division the bronchi of the third generation, etc. Bilateral bronchial anomaly means that the bronchi of the third generation are missing in an individual and are replaced by very characteristic, WO 01/15697 PC'IYSEOOI01683 irregular narrowing connections. The air exchange to and especially from the alveoli will thus be hampered by this defect bronchial structure, which is identifiable.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a means, which counteracts such obstructive lung diseases in a prophylactic or therapeutic manner.
This object is obtained by the use of at least one substance based on nicotine and/or a substance produced from said one substance for the manufacture of a medicament to be supplied to an individual of a human being or an animal for the purpose of counteracting obstructive lung diseases in a prophylactic or therapeutic manner.
The applicant has realised that nicotine, if it is not supplied via the respiration, has an inhibitory effect on the development of respiratory tract obstruction followed by the irreversible substance loss, elasticity loss and expansion of the lung tissue, i.e. the negative effects arising from pulmonary emphysema, pulmonary barotrauma and spontaneous pneumothorax. By supplying nicotine to the body of the persons suffering by pulmonary emphysema, it is thus possible to prevent or delimit the development of the disease.
Nicotine also ought to have a prophylactic effect, i.e. the origin of pulmonary emphysema of persons having a risk to be effected by this disease, for instance smokers, which have stopped smoking, may be prevented by the supply of nicotine, however not via the bronchi, respiratory organs.
The definition at least one substance based on nicotine andlor a substance produced from said one substance is to be given a broad interpretation and in this definitian are included substantially pure nicotine, nicotine compounds, nicotine related compounds, nicotine derivatives, intermediate metabalites of nicotine and/or nicotine compounds, degradation products from nicotine or nicotine compounds with completely or partly identical, similar effects.
WO 01!15697 PCT/SE00/01683 Nicotine acts via nicotine receptors partly in the vegetative system and partly in the muscles. The nicotine has firstly an irritating (vasoconstrictive) effect on the blood vessels. The vasoconstriction 5 leads to a decongestion of the mucous membrane in the respiratory tracts, which counteracts the obstruction. If nicotine is supplied in significantly higher doses than intended by the present invention, a paralysis (vessel relaxion) arises via the vegetative ganglions and the central nervous system.
According to an embodiment of the invention, the nicotine is to be supplied via the blood. It is essential that the nicotine reaches the lungs via the blood and not via the respiration. The positive effect of nicotine to the disease pulmonary emphysema can thus not be obtained if nicotine is supplied via tobacco smoke. However, it is not excluded that nicotine has a positive effect if it is supplied to the blood immediately at the same time as the patient is smoking even if the positive effect in this case will be reduced.
According to a further embodiment of the invention, the nicotine may be administered via the gastrointestinal tract, transdermally, intravascularly, intranasally or intravaginally. The nicotine may thus be supplied in various manners except via the respiratory tracts and the lungs. For instance, the nicotine may be supplied by means of plasters, spray, suppository, pills to be swallowed or in the form of chewable tablets or oral tablets, which are known in connection with smoking cessation. According to a further example, the nicotine may be administered by means of inhalation in such a way that most of the nicotine is taken up by the mucous membranes in the mouth (gastrointestinal tract).
According to a further embodiment of the invention, said substance based on nicotine and/or substances produced by said one substance are absorbed in a binding agent. Such a binding agent may permit a slow administration of the active nicotine substance, so-called "slow release".
WV Ul/1~0Y7 YC:~1~/J1GUU/U10~
According to a further embodiment of the invention, the use is intended for said individual, which has a congenital bilateral bronchial anomaly. As mentioned initially, the destruction of the lung tissue, due to smoking, may be general without anomaly or due to AAT-deficiency. The applicant has however realised that the risk of serious obstructions in the lungs, which leads to pulmonary barotrauma, such as spontaneous pneumothorax and pulmonary emphysema, is substantially higher for smokers having a congenital bilateral bronchial anomaly than for smokers not having such an anomaly. This risk ought to be in the order of 2000-3000 % higher for smokers with, than smokers without bilateral bronchial anomaly.
The formed structure of a bilateral bronchial anomaly is associated with a different function, such as ventilation, perfusion, and a high sensibility for external factors, such as smoking.
The object is also obtained by a method for prophylactic or therapeutic treatment of obstructive lung diseases of an individual of a human being or an animal, wherein said individual is supplied with a nicotine-based substance.
DESCRIPTION OF EMBODIMENTS OF THE INVENTION
Investigations have been made showing an inverted correlation between smoking habits of pregnant women and the risk of pulmonary barotrauma of the new-born children of the women.
Thus, new-born children of smoking women have a lower predisposition to get pulmonary barotrauma than new-born children of women which are not smoking. Investigations also show that foetuses of women which smoke have nicotine in the blood. This inverted relation thus indicates that nicotine may counteract obstructive lung diseases.
It is known to use nicotine, i.e. 3-(1-metyl-2-pyrrolidyl) pyridine for smoking cessation, i.e. for reducing the abstinence complaints. The use now proposed according to the present invention may thus be regarded as a second medical indication. The medical effect mentioned above may be obtained for smokers which are smoking, '7 smokers which are giving up their smoking, smokers which have giving up their smoking until this disease risk is reduced, individuals with a lung obstruction and when one wishes to reduce the obstruction in remaining parts of the lungs andlor no other treatment is available.
It is of course important that the quantity of nicotine supplied is adapted to the individual to receive the medicament. A suitable dosing for obtaining the desired effect may be 1-100 mgl24h, preferably 5-50 mgl24h, for instance 7mg/24h, 14mg/24h or 21 mg/24h. These doses refer to a medicament with nicotine in substantially pure form.
Such a dose may for instance be obtained by means of tablets of the type called "slow release". Such tablets may contain a binding agent permitting a slow release of the active nicotine substance.
The tablets are suitably designed in such a way that the patient may take one or two tablets per 24h. The dose may also be obtained by the plasters mentioned above or chewable tablets which also may contain flavouring substances, consistency agents and/or any binding agent having an ability to bind nicotine and permit the release thereof at a suitable speed. The nicotine may be present in a substantially free form in such a binding agent, be chemically bounded to any substance or any nicotine compound or as a nicotine derivative.
In contrast to the medicament for smoking cessation, there is no desire of the present invention to obtain any quick addition when the patient suffers from abstinence but rather a slow and over the time uniform dosing speed in order to obtain an equal plasma concentration and bioavailability.
The invention is not limited to the examples given but may be varied and modified within the scope of the following claims.
Claims (20)
1. Use of at least one substance based on nicotine and/or a substance produced from said one substance for the manufacture of a medicament to be supplied to an individual of a human being or an animal for the purpose of counteracting obstructive lung diseases in a prophylactic or therapeutic manner.
2. Use according to claim 1, wherein the medicament is supplied via the blood path.
3. Use according to claim 2, wherein the medicament is intended to be administered via the gastrointestinal tract.
4. Use according to claim 2, wherein the medicament is intended to be administered transdermally.
5. Use according to claim 2, wherein the medicament is intended to be administered intravascularly.
6. Use according to claim 2, wherein the medicament is intended to be administered intranasally.
7. Use according to claim 2, wherein the medicament is intended to be administered intravaginally.
8. Use according to any one of the preceding claims, wherein said purpose is to counteract pulmonary emphysema.
9. Use according to any one of the preceding claims, wherein said nicotine-based substance includes substantially pure nicotine.
10. Use according to any one of the preceding claims, wherein said nicotine-based substance includes nicotine derivative, intermediate metabolites of nicotine or degradation products of nicotine.
11. Use according to any one of the preceding claims, wherein said one substance based on nicotine and/or substances produced from said one substance are absorbed by a binding agent.
12. Use according to any one of the preceding claims, wherein said individual has a congenital bilateral bronchial anomaly.
13. A method for prophylactic or therapeutic treatment of obstructive lung diseases of in individual of a human being or an animal, wherein said individual is supplied with a nicotine-based substance.
14. A method according to claim 13, wherein the medicament is supplied via the blood path.
15. A method according to claim 14, wherein the medicament is intended to be administered via the gastrointestinal tract.
16. A method according to claim 14, wherein the medicament is intended to be administered transdermally.
17. A method according to claim 14, wherein the medicament is intended to be administered intravascularly.
18. A method according to claim 14, wherein the medicament is intended to be administered intranasally.
19. A method according to claim 14, wherein the medicament is intended to be administered intravaginally.
20. A method according to any one of claims 13 to 19, wherein said individual has a congenital bilateral bronchial anomaly.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9903085A SE516807C2 (en) | 1999-09-01 | 1999-09-01 | Use of nicotine based substances to treat obstructive lung diseases |
SE9903085-0 | 1999-09-01 | ||
SE0001075A SE0001075D0 (en) | 1999-09-01 | 2000-03-27 | Use of at least one nicotine-based substance and / or substance derived from this substance for the manufacture of a medicament and method for the treatment of obstructive pulmonary diseases |
SE0001075-1 | 2000-03-27 | ||
PCT/SE2000/001683 WO2001015697A1 (en) | 1999-09-01 | 2000-09-01 | Use of at least one substance based on nicotine and/or a substance produced from said one substance for the manufacture of a medicament, and a method for treatment of obstructive lung diseases |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2382567A1 true CA2382567A1 (en) | 2001-03-08 |
Family
ID=26655041
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002382567A Abandoned CA2382567A1 (en) | 1999-09-01 | 2000-09-01 | Use of at least one substance based on nicotine and/or a substance produced from said one substance for the manufacture of a medicament, and a method for treatment of obstructive lung disease |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1207883A1 (en) |
AU (1) | AU7047700A (en) |
CA (1) | CA2382567A1 (en) |
SE (1) | SE0001075D0 (en) |
WO (1) | WO2001015697A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006005195A1 (en) * | 2004-07-15 | 2006-01-19 | UNIVERSITé LAVAL | Nicotinic receptor agonists for the treatment of inflammatory diseases |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2341952A1 (en) | 2001-03-23 | 2002-09-23 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory pulmonary diseases |
US8039459B2 (en) | 2004-07-15 | 2011-10-18 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
US8557804B2 (en) | 2002-03-25 | 2013-10-15 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001511159A (en) * | 1997-02-07 | 2001-08-07 | シナプス・ファーマシューティカルズ・インターナショナル・インコーポレイテッド | Pharmaceutical composition for treating synaptic dysfunction containing oxime |
-
2000
- 2000-03-27 SE SE0001075A patent/SE0001075D0/en unknown
- 2000-09-01 CA CA002382567A patent/CA2382567A1/en not_active Abandoned
- 2000-09-01 EP EP00959096A patent/EP1207883A1/en not_active Withdrawn
- 2000-09-01 AU AU70477/00A patent/AU7047700A/en not_active Abandoned
- 2000-09-01 WO PCT/SE2000/001683 patent/WO2001015697A1/en not_active Application Discontinuation
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006005195A1 (en) * | 2004-07-15 | 2006-01-19 | UNIVERSITé LAVAL | Nicotinic receptor agonists for the treatment of inflammatory diseases |
KR100860903B1 (en) * | 2004-07-15 | 2008-09-29 | 유니버시티 라발 | Nicotinc Receptor Agonists for the Treatment of Inflammatory Diseases |
AU2005262174B2 (en) * | 2004-07-15 | 2009-10-08 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
AU2005262174C1 (en) * | 2004-07-15 | 2010-05-06 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
CN101001843B (en) * | 2004-07-15 | 2014-08-27 | 拉瓦尔大学 | Nicotinic receptor agonists for the treatment of inflammatory diseases |
Also Published As
Publication number | Publication date |
---|---|
SE0001075D0 (en) | 2000-03-27 |
WO2001015697A1 (en) | 2001-03-08 |
EP1207883A1 (en) | 2002-05-29 |
WO2001015697A8 (en) | 2002-01-03 |
AU7047700A (en) | 2001-03-26 |
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Legal Events
Date | Code | Title | Description |
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EEER | Examination request | ||
FZDE | Discontinued | ||
FZDE | Discontinued |
Effective date: 20070904 |
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FZDE | Discontinued |
Effective date: 20070904 |