US5179079A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Nasal formulation and intranasal administration therewith
Assignee: Novo Nordisk AS
•
Filing: 1991-11-27
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Granted: 1993-01-12
•
Expires: 2011-11-27
Abstract
Abstract The systemic absorption after intranasal administration of certain drugs, in particular pharmacologically active polypeptides is enhanced in the presence of a phospholipid, such as a phosphatidylcholine (a lecithin), preferably admixed with a vegetable oil.
Inventors
- 👤 Philip E. Hansen
- 👤 Anders R. Sorensen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:38
CPC Classifications
A; A61; A61K; A61K47/00; A61K47/06; A61K47/24; A61K47/44; A61K9/00; A61K9/0012; A61K9/0043
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
87 words
A preparation for intranasal administration characterized by containing a pharmaceutically active polypeptide and an absorption enhancing system containing a fatty oil and at least one phospholipid of the formula I ##STR2## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 2
Dependent Claim
87 words
A preparation for intranasal administration characterized by containing a pharmaceutically active polypeptide and an absorption enhancing system containing a fatty oil and at least one phospholipid of the formula I ##STR2## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 3
Dependent Claim
10 words
The preparation according to claim 1, wherein R'" is 2-(trimethylammonio)ethyl.
Claim 4
Dependent Claim
22 words
The preparation of claim 2, wherein each of R' and R" is alkyl or alkylcarbonyl containing from 4 to 12 carbon atoms.
Claim 5
Dependent Claim
12 words
The preparation of claim 3, wherein R' and R" each represents nonylcarbonyl.
Claim 6
Dependent Claim
12 words
The preparation of claim 2, wherein either R' or R" is hydrogen.
Claim 7
Dependent Claim
33 words
The preparation according to claim 1, wherein the fatty oil is a vegetable oil, selected from the group consisting of soybean oil, peanut oil, coconut oil, maize oil, olive oil and sunflower oil.
Claim 8
Dependent Claim
27 words
The preparation according to claim 1, wherein the content of phospholipid of formula I is in the range of from 0.01 to 10% (w/v) of the preparation.
Claim 9
Dependent Claim
25 words
The preparation according to claim 1, wherein the content of fatty oil is in the range of from 0.01 to 50% (w/v) of the preparation.
Claim 10
Dependent Claim
88 words
A preparation for intranasal administration characterized by containing a pharmaceutically active polypeptide and an absorption enhancing system containing from about 0.5-5% w/v of at least one phospholipid of the formula I ##STR3## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 11
Dependent Claim
88 words
A preparation for intranasal administration characterized by containing a pharmaceutically active polypeptide and an absorption enhancing system containing from about 0.5-5% w/v of at least one phospholipid of the formula I ##STR3## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 12
Dependent Claim
10 words
The preparation of claim 9, wherein the polypeptide is glucagon.
Claim 13
Dependent Claim
104 words
A preparation for intranasal administration characterized by containing insulin, an insulin derivative, a mixture of insulin and at least one insulin derivative, or a mixture of insulin derivatives and an absorption enhancing system containing from about 0.5-5% w/v of at least one phospholipid of the formula I ##STR4## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 14
Dependent Claim
104 words
A preparation for intranasal administration characterized by containing insulin, an insulin derivative, a mixture of insulin and at least one insulin derivative, or a mixture of insulin derivatives and an absorption enhancing system containing from about 0.5-5% w/v of at least one phospholipid of the formula I ##STR4## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 15
Dependent Claim
26 words
A preparation according to claim 11 having an insulin activity content in the range of from 5 to 1000 international units per ml of the preparation.
Claim 16
Dependent Claim
91 words
A treatment method which comprises intranasally administering to one in need of treatment a preparation containing a pharmaceutically active peptide and from about 0.1-10% w/v of at least one phospholipid of the formula I ##STR5## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 17
Dependent Claim
91 words
A treatment method which comprises intranasally administering to one in need of treatment a preparation containing a pharmaceutically active peptide and from about 0.1-10% w/v of at least one phospholipid of the formula I ##STR5## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 18
Dependent Claim
13 words
The method of claim 13 wherein the preparation further contains a fatty oil.
Claim 19
Dependent Claim
32 words
The method of claim 14 wherein the fatty oil is a vegetable oil selected from the group consisting of soybean oil, peanut oil, coconut oil, maize oil, olive oil and sunflower oil.
Claim 20
Dependent Claim
24 words
The method of claim 13 wherein the pharmaceutically active peptide is selected from the group consisting of glucagon and insulin or an insulin derivative.
Claim 21
Independent Claim
105 words
A method for treating a diabetic which comprises intranasally administering thereto a preparation containing insulin, an insulin derivative, a mixture of insulin and at least one insulin derivative, or a mixture of insulin derivatives and from about 0.01-10% w/v of at least one phospholipid of the formula I ##STR6## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
Claim 22
Independent Claim
105 words
A method for treating a diabetic which comprises intranasally administering thereto a preparation containing insulin, an insulin derivative, a mixture of insulin and at least one insulin derivative, or a mixture of insulin derivatives and from about 0.01-10% w/v of at least one phospholipid of the formula I ##STR6## wherein R' and R" are the same or different each representing hydrogen, alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl or alkatetraenylcarbonyl containing not more than 14 carbon atoms with the proviso that both R' and R" are not hydrogen, and R'" represents a hydrophilic group selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxypropyl or 2,3,4,5,6-pentahydroxycyclohexyl.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1996-01-12 | 1996-07-13 | 1997-01-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-01-12 | 2000-07-13 | 2001-01-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-01-12 | 2004-07-13 | 2005-01-12 | $7700.00 | Window Closed / Lapsed |