Patent US4416872A successfully refreshed from Google Patents.
US4416872A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Treatment of malaria with liposomes containing 8-aminoquinoline derivatives and glycoconjugates
Assignee: United States Department of the Army
•
Filing: 1982-03-17
•
Granted: 1983-11-22
•
Expires: 2002-03-17
Abstract
Abstract A novel treatment has been discovered for interrupting the life cycle of the malaria parasite during its development in the liver of the vertebrate host. The subject invention involves a method of chemotherapy against sporozoite-induced malaria by administering an 8-aminoquinoline drug, such as primaquine, encapsulated within liposomes containing glycoconjugates, to a vertebrate host which has been infected with sporozoites of the parasites. Preferred species of glycoconjugates have a terminal glucose or galactose moiety, such as present in glycosyl ceramide, galactosyl ceramide, lactosyl ceramide, or in glycoproteins.
Inventors
- 👤 Carl R. Alving
- 👤 Edgar A. Steck
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 10:23
CPC Classifications
A; A61; A61K; A61K31/00; A61K38/00; A61K38/16; A61K38/17; A61K38/1703; A61K38/1709; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; Y; Y02; Y02A; Y02A50/00; Y02A50/30
Claims Analysis
Total Claims: 66
Claim 1
Independent Claim
241 words
A An antimalarial composition comprising a glycoconjugate selected from the group consisting of: (a) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl; (b) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; (c) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; (d) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof; and (e) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 2
Dependent Claim
241 words
A An antimalarial composition comprising a glycoconjugate selected from the group consisting of: (a) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl; (b) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; (c) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; (d) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof; and (e) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 3
Dependent Claim
142 words
The composition of claim 1 wherein the glycoconjugate is selected from the group consisting of: (a) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl; (b) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipatic compound-containing liposome; and (c) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 4
Dependent Claim
26 words
The composition of claim 2 wherein the glycoconjugate is a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glycosyl, galactosyl and lactosyl.
Claim 5
Dependent Claim
51 words
The composition of claim 2 wherein the glycoconjugate is a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glycosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome.
Claim 6
Dependent Claim
74 words
The composition of claim 2 wherein the glycoconjugate is a glycolipid which contains a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a lipsome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 7
Dependent Claim
10 words
The composition of claim 3 wherein the glycolipid is ceramide.
Claim 8
Dependent Claim
10 words
The composition of claim 4 wherein the glycolipid is ceramide.
Claim 9
Dependent Claim
10 words
The composition of claim 5 wherein the glycolipid is ceramide.
Claim 10
Dependent Claim
11 words
The composition of claim 6 wherein the carbohydrate moiety is glucosyl.
Claim 11
Dependent Claim
11 words
The composition of claim 6 wherein the carbohydrate moiety is galactosyl.
Claim 12
Dependent Claim
11 words
The composition of claim 6 wherein the carbohydrate moiety is lactosyl.
Claim 13
Dependent Claim
11 words
The composition of claim 7 wherein the carbohydrate moiety is glucosyl.
Claim 14
Dependent Claim
10 words
The composition of claim 7 wherein the carbohydrate is galactosyl.
Claim 15
Dependent Claim
10 words
The composition of claim 7 wherein the carbohydrate is lactosyl.
Claim 16
Dependent Claim
10 words
The composition of claim 8 wherein the carbohydrate is glycosyl.
Claim 17
Dependent Claim
10 words
The composition of claim 8 wherein the carbohydrate is galactosyl.
Claim 18
Dependent Claim
10 words
The composition of claim 8 wherein the carbohydrate is lactosyl.
Claim 19
Dependent Claim
18 words
The composition of claim 16 wherein the liposome contains a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound.
Claim 20
Dependent Claim
20 words
The composition of claim 18 wherein the phospholipid is beta, gamma-dipalmitoylphosphatidylcholine and the charged (lipophilic) amphipathic compound is diacetyl phosphate.
Claim 21
Dependent Claim
11 words
The composition of claim 19 wherein the 8-aminoquinoline is primaquine diphosphate.
Claim 22
Dependent Claim
102 words
The composition of claim 1 wherein the glycoconjugate is selected from the group consisting of: (a) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a lipsome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; and (b) a glycoprotein selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 23
Dependent Claim
48 words
The composition of claim 21 wherein the glycoconjugate is a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome.
Claim 24
Dependent Claim
69 words
The composition of claim 21 wherein the glycoconjugate is a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome containins an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 25
Dependent Claim
31 words
The composition of claim 1 wherein the liposome is selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome.
Claim 26
Dependent Claim
13 words
The composition of claim 24 wherein the liposome contains a phospholipid and cholesterol.
Claim 27
Dependent Claim
22 words
The composition of claim 24 wherein the liposome contains a phospholipid, cholesterol and the additional charged lipid is a (lipophilic) amphipathic compound.
Claim 28
Dependent Claim
25 words
The composition of claim 25 wherein the phospholipid is selected from the group consisting of a phosphatidylcholine derivative, glycerophosphatide, a lysophosphatide, spingomyelin and mixtures thereof.
Claim 29
Dependent Claim
26 words
The composition of claim 26 wherein the phospholipid is selected from the group consisting of a phosphatidyl choline derivative, glycerophosphatide, a lysophosphatide, spingomyelin and mixtures thereof.
Claim 30
Dependent Claim
14 words
The composition of claim 26 wherein the charged amphipathic lipid compound is negatively charged.
Claim 31
Dependent Claim
14 words
The composition of claim 26 wherein the charged amphipathic lipid compound is positively charged.
Claim 32
Dependent Claim
27 words
The composition of claim 29 wherein the charged amphipathic lipid compound is selected from the group comprising a di(alkyl) phosphate, a phospholipid, phosphatidic acid, phosphatidylserine, and phosphatidylinositoyl.
Claim 33
Dependent Claim
22 words
The composition of claim 30 wherein the charged amphipathic lipid compound is selected from the group comprising long-chain alkylamines, stearylamine, and hexadecylamine.
Claim 34
Independent Claim
260 words
A method for treating malaria which comprises the step of administering to an infected animal a therapeutically effective amount of an antimalarial composition comprising a glycoconjugate selected from the group consisting of: (a) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl; (b) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of gucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; (c) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; (d) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glycosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof; and (e) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholip and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-quinoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 35
Independent Claim
260 words
A method for treating malaria which comprises the step of administering to an infected animal a therapeutically effective amount of an antimalarial composition comprising a glycoconjugate selected from the group consisting of: (a) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl; (b) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of gucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; (c) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; (d) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glycosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof; and (e) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholip and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-quinoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 36
Dependent Claim
131 words
The method of claim 33 wherein the glycoconjugate is selected from the group consisting of: (a) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl; (b) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; and (c) a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glycosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound containing liposome wherein each said liposome contains an 8-aminoquinoline selected
Claim 37
Dependent Claim
26 words
The method of claim 34 wherein the glycoconjugate is a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl.
Claim 38
Dependent Claim
51 words
The method of claim 34 wherein the glycoconjugate is a glycolipid having a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome.
Claim 39
Dependent Claim
74 words
The method of claim 34 wherein the glycoconjugate is a glycolipid which contains a terminal carbohydrate moiety selected from the group consisting of glucosyl, galactosyl and lactosyl encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 40
Dependent Claim
10 words
The method of claim 35 wherein the glycolipid is ceramide.
Claim 41
Dependent Claim
10 words
The method of claim 36 wherein the glycolipid is ceramide.
Claim 42
Dependent Claim
10 words
The method of claim 37 wherein the glycolipid is ceramide.
Claim 43
Dependent Claim
11 words
The method of claim 38 wherein the carbohydrate moiety is glucosyl.
Claim 44
Dependent Claim
11 words
The method of claim 38 wherein the carbohydrate moiety is galactosyl.
Claim 45
Dependent Claim
11 words
The method of claim 38 wherein the carbohydrate moiety is lactosyl.
Claim 46
Dependent Claim
11 words
The method of claim 39 wherein the carbohydrate moiety is glucosyl.
Claim 47
Dependent Claim
10 words
The method of claim 39 wherein the carbohydrate is galactosyl.
Claim 48
Dependent Claim
10 words
The method of claim 39 wherein the carbohydrate is lactosyl.
Claim 49
Dependent Claim
10 words
The method of claim 40 wherein the carbohydrate is glucosyl.
Claim 50
Dependent Claim
10 words
The method of claim 40 wherein the carbohydrate is galactosyl.
Claim 51
Dependent Claim
10 words
The method of claim 40 wherein the carbohydrate is lactosyl.
Claim 52
Dependent Claim
18 words
The method of claim 48 wherein the liposome contains a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound.
Claim 53
Dependent Claim
20 words
The method of claim 50 wherein the phospholip is beta, gamma-dipalmitoylphosphatidylcholine and the charged (lipophilic) amphipathic compound is diacetyl phosphate.
Claim 54
Dependent Claim
11 words
The method of claim 51 wherein the 8-aminoquinoline is primaquine diphosphate.
Claim 55
Dependent Claim
102 words
The method of claim 33 wherein the glycoconjugate is selected from the group consisting of: (a) a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome; and (b) a glycoprotein selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 56
Dependent Claim
48 words
The method of claim 53 wherein the glyconconjugate is a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome.
Claim 57
Dependent Claim
69 words
The method of claim 53 wherein the glyconconjugate is a glycoprotein selected from the group consisting of fetuin, asialofetuin, orosomucoid and asialoorosomucoid encapsulated within a liposome selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome wherein each said liposome contains an 8-aminoquinoline selected from the group consisting of primaquine and a pharmaceutically-acceptable acid addition salt thereof.
Claim 58
Dependent Claim
31 words
The method of claim 33 wherein the liposome is selected from the group consisting of a phospholipid and cholesterol-containing liposome, and a phospholipid, cholesterol and a charged (lipophilic) amphipathic compound-containing liposome.
Claim 59
Dependent Claim
13 words
The method of claim 56 wherein the liposome contains a phospholipid and cholesterol.
Claim 60
Dependent Claim
22 words
The method of claim 56 wherein the liposome contains a phospholipid, cholesterol and the additional charged lipid is a (lipophilic) amphipathic compound.
Claim 61
Dependent Claim
25 words
The method of claim 57 wherein the phospholipid is selected from the group consisting of a phosphatidylcholine derivative, glycerophosphatide, a lysophosphatide, spingamyelin and mixtures thereof.
Claim 62
Dependent Claim
26 words
The method of claim 58 wherein the phospholipid is selected from the group consisting of a phosphatidyl choline derivative, glycerophosphatide, a lysophosphatide, spingomyelin and mixtures thereof.
Claim 63
Dependent Claim
14 words
The method of claim 58 wherein the charged amphipathic lipid compound is negatively charged.
Claim 64
Dependent Claim
14 words
The method of claim 58 wherein the charged amphipathic lipid compound is positively charged.
Claim 65
Dependent Claim
27 words
The method of claim 61 wherein the charged amphipathic lipid compound is selected from the group comprising a di(alkyl) phosphate, a phospholipid, phosphatidic acid, phosphatidylserine, and phosphatidylinositol.
Claim 66
Dependent Claim
22 words
The method of claim 62 wherein the charged amphipathic lipid compound is selected from the group comprising long-chain alkylamines, stearylamine, and hexadecylamine.
References Cited (Backward Citations)
US3993754A
Cited
US4224179A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-11-21 | 1987-05-23 | 1987-11-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-11-21 | 1991-05-23 | 1991-11-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-11-21 | 1995-05-23 | 1995-11-22 | $7700.00 | Window Closed / Lapsed |