EP0245366A1 - Method and composition for blocking antigen-induced allergic responses - Google Patents
Method and composition for blocking antigen-induced allergic responsesInfo
- Publication number
- EP0245366A1 EP0245366A1 EP19860906675 EP86906675A EP0245366A1 EP 0245366 A1 EP0245366 A1 EP 0245366A1 EP 19860906675 EP19860906675 EP 19860906675 EP 86906675 A EP86906675 A EP 86906675A EP 0245366 A1 EP0245366 A1 EP 0245366A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- antigen
- subject
- induced allergic
- methylene
- allergic response
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000000427 antigen Substances 0.000 title claims abstract description 36
- 102000036639 antigens Human genes 0.000 title claims abstract description 36
- 108091007433 antigens Proteins 0.000 title claims abstract description 36
- 208000026935 allergic disease Diseases 0.000 title claims description 30
- 238000000034 method Methods 0.000 title claims description 21
- 230000000903 blocking effect Effects 0.000 title claims description 17
- 239000000203 mixture Substances 0.000 title claims description 13
- 239000005557 antagonist Substances 0.000 claims abstract description 6
- 208000010668 atopic eczema Diseases 0.000 claims description 13
- 208000003251 Pruritus Diseases 0.000 claims description 11
- 239000003401 opiate antagonist Substances 0.000 claims description 8
- 206010006482 Bronchospasm Diseases 0.000 claims description 7
- 208000024780 Urticaria Diseases 0.000 claims description 7
- 230000000172 allergic effect Effects 0.000 claims description 7
- 230000007885 bronchoconstriction Effects 0.000 claims description 7
- 208000028185 Angioedema Diseases 0.000 claims description 6
- 201000004624 Dermatitis Diseases 0.000 claims description 6
- 238000011010 flushing procedure Methods 0.000 claims description 6
- 206010039083 rhinitis Diseases 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 3
- 239000003887 narcotic antagonist Substances 0.000 abstract description 3
- 241001494479 Pecora Species 0.000 description 13
- 208000006673 asthma Diseases 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 4
- 229960004127 naloxone Drugs 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229940005483 opioid analgesics Drugs 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 241000244188 Ascaris suum Species 0.000 description 2
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229960001761 chlorpropamide Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical class C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 241000656145 Thyrsites atun Species 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- 229960005297 nalmefene Drugs 0.000 description 1
- 229960003086 naltrexone Drugs 0.000 description 1
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002627 tracheal intubation 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
Definitions
- the present invention is directed to a method and composition for blocking antigen-induced allergic responses. More particularly, the invention is concerned with blocking such responses through adminis ⁇ tration of a pure opioid antagonist.
- BACKGROUND OF THE INVENTION A large segment of the population suffers from antigen-induced allergies. Typical allergic responses include rhinitis, urticaria, eczema, skin flushing, pruritis, angioedema and bronchoconstriction (asthma) . A host of preparations are available to persons suffering from allergies. Desirable qualities for relief of allergic symptoms include effectiveness of relief, length of effective action and safety of active ingredient.
- naloxone mycosis funsoides, intractable pruritis and the like by injection of naloxone.
- Parenteral administration of naloxone for treating antigen-induced itch, asthma, urticaria and angioedema- is disclosed by S itz et al, Am. Intern. Med., 97(5), 788-9 (1982).
- a first aspect of this invention is directed to a metir ⁇ d for blocking an antigen-induced allergic response iir. a subject comprising administering to said subject an amount, of the compound 6- methylene-6-desoxy-n-cyclo- propylmethyl-14-hydroxydihydronormorphine in an amount sufficient to inhibit the antigen-induced allergic response.
- this invention provides a method for blocking an antigen-induced allergic response of the group consisting of bronchoconstriction, rhinitis, urticaria, eczema, skin flushing, angioedema and pruritis in a subje ⁇ t, comprising administering to the subject an amount of the compound 6-methylene-6- desoxy-n-cyclopro ⁇ ylmeth l-14-hydroxydihydronormorphine sufficient to inhibit the antigen-induced allergic response.
- a further embodiment includes a composition for blocking an antigen-induced allergic reponse in a subject, comprising: an amount of 6-methylene-6-desoxy-n-cyclopropyl- methyl-14-hydroxydihydronormorphine sufficient to inhibit the antigen-induced allergic response in the subject; and a pharmaceutically acceptable carrier therefor.
- Yet another aspect of the invention provides a method for blocking an antigen-induced allergic response in a subject, comprising orally administering to the subject a pure opioid antagonist in an amount sufficient to inhibit the antigen-induced allergic response.
- a still further embodiment is directed to an oral composition for blocking an antigen-induced allergic response in a subject comprising: an amount of pure opioid antagonist sufficient to block the antigen-induced allergic response in the subject; and a pharmaceutically acceptable oral carrier therefor.
- the present invention is directed to blocking antigen-induced allergic responses with an opioid antagonist.
- the antagonist may be administered prophyl- actically or remedially. Oral administration is preferred for its convenience, especially for prophylac ⁇ tic uses. It is preferred that a pure opioid antagonist be used, so that any opioid-like side effects are avoided.
- a preferred group of pure opioid antagonists is disclosed in U.S. Patents 3,814,768 and 3,896,226, the disclosures of which are incorporated herein by refer- ence.
- 6-methylene-6-desoxy- n-cyclopropylmethyl-14-hydroxydihydronormorphine USAN- nalmefene
- Other antagonists also are useful, such as naltrexone.
- the opioid antagonists are useful in blocking a wide variety of antigen-induced allergic responses. Such responses include bronchoconstriction, rhinitis, urticaria, eczema, skin flushing, angioedema and pruritis. Of these, bronchoconstriction is believed to be the most pervasive antigen-induced allergic response.
- the present invention is useful in both preventing and alleviating such responses.
- Oral administration is preferred for its conven- ience. However, faster action could be obtained through parenteral or pulmonary administration.
- Pulmonary administration preferably is accomplished through use of a metered dose inhaler and an inhalation device as disclosed in Sackner et. al. U.S. Patent 4,484,577, the disclosure of which is incorporated herein by reference.
- Oral administration may be through tablets or capsules formed from conventional formulating ingredients.
- the amount of active ingredient administered is about 1-60 mg per day, preferably about 2-20 mg per day, more- preferably about 10 mg per day.
- Oral dosage unit forms can contain suitable amounts of active ingredient to meet these dosages, preferably about 2-20 mg per dosage unit, more prefer ⁇ ably about 10 mg per dosage unit.
- the safety and efficacy of the active ingredient particularly when it is 6-methylene-6-desoxy-n-cyclopropylmethyl-14-hydroxy- dihydronormorphine, make the present invention useful in treating or preventing both mild and severe allergic responses.
- EXAMPLE Experiments are conducted on five adult sheep which are allergic to ascaris suum extract.
- the experimental method is from Abraham et al. (Am. Rev. Resp. Pis. 128:839-844). Allergic response to the antigen was confirmed by cutaneous reaction to the antigen injected dermally into each sheep. The antigen challenge to the lungs is delivered by aerosol.
- An aerosol containing ascaris suum extract (1:20) is generated with a disposable nebulizer. The output from the nebulizer is connected to an endo- tracheal tube located in the sheep's trachea. Specific resistance to airflow in the lung is determined before and after aerosol delivery of the antigen.
- Airflow resistance in the lung is measured as follows. The sheep remain unsedated with their heads restrained. The nasal passages treated with a two percent lidocaine local anesthetic. A balloon catheter is then threaded through one nostril and into the lower esophogus. Intubation is done with a cuffed endotra- cheal tube through the other nostril. The cuff of the tube is inflated only during measurements of airway mechanics. An esophageal balloon catheter provides for measurement of pleural pressure. Pressure in the trachea is measured from a side hole catheter at the distal tip of the nasal tracheal tube. A differential pressure transducer measures the transpulmonary pressure and the difference between tracheal pressure and pleural pressure.
- Airflow resistance is measured by connecting the nasal tracheal tube to a pneumotachograph. Trans ⁇ pulmonary pressure and flow are registered on an oscilloscope recorder. Five to ten breathes are used for each determination of airflow resistance, with resistance equalling pressure difference/flow. Baseline measurements of airflow resistance are made before and after intravenous injection of 6- methylene-6-desoxy-n-cyclopropylmeth l-14-hydroxydi- hydronormorphine. In two sheep, a dose of 0.05 mg/kg is used while in three other sheep the doses are 0.1, 0.2 and 0.5 mg/kg, respectively. Intravenous administration is used since the active ingredient does not show good bioavailability in sheep upon oral administration, despite the good oral bioavailability in humans.
- the opioid antagonist was effective in blocking antigen-induced bronchoconstric- tion. Near total block was provided in four of the five sheep. In the remaining sheep, the response in airway resistance was decreased by about 70%, from 726% to 233%.
Abstract
Des réactions allergiques provoquées par des antigènes sont inhibées par l'administration d'antagonistes opioïdes. Un antagoniste préféré est la 6-méthylène-6-désoxy-n-cyclopropylméthyle-14-hydroxydihydronormorphine. Une administration par voie orale est préférée.Allergic reactions caused by antigens are inhibited by the administration of opioid antagonists. A preferred antagonist is 6-methylene-6-deoxy-n-cyclopropylmethyl-14-hydroxydihydronormorphine. Oral administration is preferred.
Description
METHOD AND COMPOSITION FOR BLOCKING ANTIGEN-INDUCED ALLERGIC RESPONSES FIELD OF THE INVENTION The present invention is directed to a method and composition for blocking antigen-induced allergic responses. More particularly, the invention is concerned with blocking such responses through adminis¬ tration of a pure opioid antagonist.
BACKGROUND OF THE INVENTION A large segment of the population suffers from antigen-induced allergies. Typical allergic responses include rhinitis, urticaria, eczema, skin flushing, pruritis, angioedema and bronchoconstriction (asthma) . A host of preparations are available to persons suffering from allergies. Desirable qualities for relief of allergic symptoms include effectiveness of relief, length of effective action and safety of active ingredient.
It is known that opioids can precipitate asthma attacks in anesthetized patients, and that morphine and related opioids are to be avoided during asthma attacks. It also is known that morphine causes itching, which may be related to degranulation of mast cells. Degranula- tion of mast cells is believed to play a central role in causing allergic responses.
Bernstein and Swift (Arch. Dermatol. 115: 1366, Nov. 1979) showed that subcutaneous administration of naloxone blocked pruritis caused by primary bilary cirrhosis. Leslie, Bellamy and Pike (Br. Med. J. 280: 16-18, Jan. 5, 1980) showed that intravenous naloxone blocked, asthma precipitated by chloropropamide and alcohol. It is believed 'that chloropropamide and alco¬ hol cause release of endogenous opioids. The same article showed that administering an enkephalin analog with opioid-like activity precipitated asthma in one patient. Bernstein U.S. Patent 4,181,726 discloses treatment of itching associated with Hodgkin's disease.
mycosis funsoides, intractable pruritis and the like by injection of naloxone. Parenteral administration of naloxone for treating antigen-induced itch, asthma, urticaria and angioedema- is disclosed by S itz et al, Am. Intern. Med., 97(5), 788-9 (1982).
SUMMARY OF THE INVENTION A first aspect of this invention is directed to a metirαd for blocking an antigen-induced allergic response iir. a subject comprising administering to said subject an amount, of the compound 6- methylene-6-desoxy-n-cyclo- propylmethyl-14-hydroxydihydronormorphine in an amount sufficient to inhibit the antigen-induced allergic response.
In a second embodiment, this invention provides a method for blocking an antigen-induced allergic response of the group consisting of bronchoconstriction, rhinitis, urticaria, eczema, skin flushing, angioedema and pruritis in a subjeσt, comprising administering to the subject an amount of the compound 6-methylene-6- desoxy-n-cycloproρylmeth l-14-hydroxydihydronormorphine sufficient to inhibit the antigen-induced allergic response.
A further embodiment includes a composition for blocking an antigen-induced allergic reponse in a subject, comprising: an amount of 6-methylene-6-desoxy-n-cyclopropyl- methyl-14-hydroxydihydronormorphine sufficient to inhibit the antigen-induced allergic response in the subject; and a pharmaceutically acceptable carrier therefor.
Yet another aspect of the invention provides a method for blocking an antigen-induced allergic response in a subject, comprising orally administering to the subject a pure opioid antagonist in an amount sufficient to inhibit the antigen-induced allergic response.
A still further embodiment is directed to an oral
composition for blocking an antigen-induced allergic response in a subject comprising: an amount of pure opioid antagonist sufficient to block the antigen-induced allergic response in the subject; and a pharmaceutically acceptable oral carrier therefor.
DETAILED DESCRIPTION OF THE INVENTION The present invention is directed to blocking antigen-induced allergic responses with an opioid antagonist. The antagonist may be administered prophyl- actically or remedially. Oral administration is preferred for its convenience, especially for prophylac¬ tic uses. It is preferred that a pure opioid antagonist be used, so that any opioid-like side effects are avoided. A preferred group of pure opioid antagonists is disclosed in U.S. Patents 3,814,768 and 3,896,226, the disclosures of which are incorporated herein by refer- ence. Particularly preferred is 6-methylene-6-desoxy- n-cyclopropylmethyl-14-hydroxydihydronormorphine (USAN- nalmefene) , which has been found to be quite safe and highly effective, and exhibits a longer period of activity than other antagonists. Other antagonists also are useful, such as naltrexone.
The opioid antagonists are useful in blocking a wide variety of antigen-induced allergic responses. Such responses include bronchoconstriction, rhinitis, urticaria, eczema, skin flushing, angioedema and pruritis. Of these, bronchoconstriction is believed to be the most pervasive antigen-induced allergic response. The present invention is useful in both preventing and alleviating such responses.
Oral administration is preferred for its conven- ience. However, faster action could be obtained through parenteral or pulmonary administration. Pulmonary administration preferably is accomplished through use of
a metered dose inhaler and an inhalation device as disclosed in Sackner et. al. U.S. Patent 4,484,577, the disclosure of which is incorporated herein by reference. Oral administration may be through tablets or capsules formed from conventional formulating ingredients.
The amount of active ingredient administered is about 1-60 mg per day, preferably about 2-20 mg per day, more- preferably about 10 mg per day. Oral dosage unit forms,. e..g. , tablets or capsules, can contain suitable amounts of active ingredient to meet these dosages, preferably about 2-20 mg per dosage unit, more prefer¬ ably about 10 mg per dosage unit. The safety and efficacy of the active ingredient, particularly when it is 6-methylene-6-desoxy-n-cyclopropylmethyl-14-hydroxy- dihydronormorphine, make the present invention useful in treating or preventing both mild and severe allergic responses.
EXAMPLE Experiments are conducted on five adult sheep which are allergic to ascaris suum extract. The experimental method is from Abraham et al. (Am. Rev. Resp. Pis. 128:839-844). Allergic response to the antigen was confirmed by cutaneous reaction to the antigen injected dermally into each sheep. The antigen challenge to the lungs is delivered by aerosol. An aerosol containing ascaris suum extract (1:20) is generated with a disposable nebulizer. The output from the nebulizer is connected to an endo- tracheal tube located in the sheep's trachea. Specific resistance to airflow in the lung is determined before and after aerosol delivery of the antigen.
Airflow resistance in the lung is measured as follows. The sheep remain unsedated with their heads restrained. The nasal passages treated with a two percent lidocaine local anesthetic. A balloon catheter is then threaded through one nostril and into the lower esophogus. Intubation is done with a cuffed endotra-
cheal tube through the other nostril. The cuff of the tube is inflated only during measurements of airway mechanics. An esophageal balloon catheter provides for measurement of pleural pressure. Pressure in the trachea is measured from a side hole catheter at the distal tip of the nasal tracheal tube. A differential pressure transducer measures the transpulmonary pressure and the difference between tracheal pressure and pleural pressure. Airflow resistance is measured by connecting the nasal tracheal tube to a pneumotachograph. Trans¬ pulmonary pressure and flow are registered on an oscilloscope recorder. Five to ten breathes are used for each determination of airflow resistance, with resistance equalling pressure difference/flow. Baseline measurements of airflow resistance are made before and after intravenous injection of 6- methylene-6-desoxy-n-cyclopropylmeth l-14-hydroxydi- hydronormorphine. In two sheep, a dose of 0.05 mg/kg is used while in three other sheep the doses are 0.1, 0.2 and 0.5 mg/kg, respectively. Intravenous administration is used since the active ingredient does not show good bioavailability in sheep upon oral administration, despite the good oral bioavailability in humans.
The results of the tests are shown in the table below.
Table 1 PERCENT INCREASE IN AIR FLOW RESISTANCE IN RESPONSE TO ANTIGEN
Before Treatment Dose After Treatment
Sheep #1 144% 0.05 mg/kg 39%
Sheep #2 674% 0.05 mg/kg 0%
Sheep #3 726% 0.1 mg/kg 233%
Sheep #4 699% 0.2 mg/kg 6% S Shheeeepp ##55 4 49977%% 0 0..55 mmgg//kkgg 5%
It can be seen that the opioid antagonist was effective in blocking antigen-induced bronchoconstric-
tion. Near total block was provided in four of the five sheep. In the remaining sheep, the response in airway resistance was decreased by about 70%, from 726% to 233%. Although a detailed description of the present invention has been provided above, the invention is not limited thereto, but rather is defined by the following claims.
Claims
1. A method for blocking an antigen-induced allergic response in a subject, comprising administering to said subject the compound 6-methylene-6-desoxy-n- cyclopropylmethyl-14-hydroxydihydronormorphine sufficient to inhibit said antigen-induced allergic response.
2. The method of claim 1, wherein said 6- methylene-6-desoxy-n-cyclopropylmeth l-14-hydroxydi- hydronormorphine is administered orally.
3. The method of claim 1, wherein the amount administered is from about 1 to about 60 mg per day.
4. The method of claim 1, wherein the 6-methylene- 6-desoxy-n-cyclopropylmethyl-14-hydroxydihydronormor- phine is administered to the subject prophylactically.
5. The method of claim 1, wherein the 6-methylene- 6-desoxy-n-cyclopropylmethyl-14-hydroxydihydronormor- phine is administered to provide relief to a subject suffering from the antigen-induced allergic reponse.
6. A method for blocking an antigen-induced allergic response of the group consisting of broncho¬ constriction, rhinitis, urticaria, eczema, skin flushing, angioedema and pruritis in a subject, comprising administering to said subject an amount of the compound 6-methylene-6-desoxy-n-cyclopropylmethyl- 14-hydroxy-dihydronormorphine sufficient to inhibit the antigen-induced allergic response.
7. The method of claim 6, wherein said 6- methylene-6-desoxy-n-cyclopropylmethyl-14-hydroxydi- hydronormorphine is administered orally.
8. The method of claim 6, wherein the amount administered is from about 1 to about 60 mg per day.
9. The method of claim 8, wherein the amount is about 2 to about 20 mg per day.
10. The method of claim 9, wherein the amount is about 10 mg per day.
11. The method of claim 6, wherein the 6-methylene- 6-desoxγ-n-cyclopropylmethyl-14-hydroxydihydronormor- phine is administered prophylactically.
12. The method of claim 6, wherein the 6-methylene- 6-desoxy-n-cyclopropylmethyl-14-hydroxydihydronormor- phine is administered to provide relief to a subject suffering from the antigen-induced allergic reponse.
13. The method of claim 6, wherein the antigen- induced allergic response is bronchoconstriction.
14. A composition for blocking an antigen-induced " allergic reponse in a subject, comprising: an. amount of 6-methylene-6-desoxy-n-cyclopropyl- methyl-14-hydroxydihydronormorphine sufficient to inhibit the antigen-induced allergic response in the subject; and a pharmaceutically acceptable carrier therefor.
15. The composition of claim* 14, wherein said carrier is suitable for oral administration.
16. The composition of claim 15, wherein said composition is in a single dosage unit form.
17. The composition of claim 16, wherein the amount of 6-methylene-6-desoxy-n-cyclopropylmethyl-14-hydroxy- dihydronormorphine in the dosage unit is about 2-20 mg.
18. A method for blocking an antigen-induced allergic response in a subject, comprising orally administering to the subject a pure opioid antagonist in an amount sufficient to inhibit said antigen-induced allergic response.
19. The method of claim 18, wherein said antagonist is administered orally in the amount of about 1-60 mg per day.
20. The method of claim 18, wherein the antigen- induced allergic response is of the group consisting of bronchoconstriction, rhinitis, urticaria, eczema, skin flushing, and pruritis.
21. An oral composition for blocking an antigen- induced allergic response in a subject comprising: an amount of pure opioid antagonist sufficient to block the antigen-induced allergic response in the subject; and a pharmaceutically acceptable oral carrier therefor.
22. The composition of claim 21, wherein the amount of antagonist is about 2-20 mg.
23. The composition of claim 19, wherein the antigen—induced allergic response is of the group consisting: of bronchoconstric¬ tion, rhinitis, urticaria, eczema, skin flushing, angioedema and pruritis.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79258785A | 1985-10-29 | 1985-10-29 | |
| US792587 | 1985-10-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0245366A1 true EP0245366A1 (en) | 1987-11-19 |
Family
ID=25157410
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19860906675 Withdrawn EP0245366A1 (en) | 1985-10-29 | 1986-10-27 | Method and composition for blocking antigen-induced allergic responses |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0245366A1 (en) |
| JP (1) | JPS63501717A (en) |
| CA (1) | CA1287301C (en) |
| WO (1) | WO1987002586A2 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946848A (en) * | 1985-10-29 | 1990-08-07 | Baker Cumins Dermatologicals, Inc. | Method of treating pruritus with nalmefene and clonidine |
| US4880813A (en) * | 1988-07-22 | 1989-11-14 | Baker Cummins Pharmaceuticals, Inc. | Method of treatment for allergic rhinitis |
| US4877791A (en) * | 1988-11-01 | 1989-10-31 | Baker Cummins Pharmaceuticals, Inc. | Method of treatment for interestitial cystitis |
| US4923875A (en) * | 1989-07-10 | 1990-05-08 | Baker Cummins Pharmaceuticals, Inc. | Method for treatment of mast cell-mediated dermatologic disorders |
| US5057322A (en) * | 1990-08-10 | 1991-10-15 | Baker Cummins Dermatologicals, Inc. | Method of treating mast cell disease |
| US5116847A (en) * | 1991-01-25 | 1992-05-26 | The Procter & Gamble Company | Use of loperamide and related compounds for treatment of respiratory disease symptoms |
| GB9908921D0 (en) * | 1999-04-19 | 1999-06-16 | Britannia Pharmaceuticals Ltd | Spray dispenser for opiod antagonists |
| US7501433B2 (en) | 2002-05-17 | 2009-03-10 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US8017622B2 (en) | 2003-05-16 | 2011-09-13 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| CN102415993B (en) * | 2011-12-03 | 2013-01-09 | 武汉同源药业有限公司 | Pharmaceutical composition containing nalmefene hydrochloride and preparation method of same |
-
1986
- 1986-10-27 JP JP50591086A patent/JPS63501717A/en active Pending
- 1986-10-27 EP EP19860906675 patent/EP0245366A1/en not_active Withdrawn
- 1986-10-27 WO PCT/US1986/002268 patent/WO1987002586A2/en not_active Application Discontinuation
- 1986-10-28 CA CA000521587A patent/CA1287301C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63501717A (en) | 1988-07-14 |
| CA1287301C (en) | 1991-08-06 |
| WO1987002586A2 (en) | 1987-05-07 |
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