US4603124A
Expired / Lapsed
US
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Surfactant and pharmaceutical compositions containing same
Assignee: TT Pharmaceuticals Inc
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Filing: 1984-02-27
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Granted: 1986-07-29
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Expires: 2004-02-27
Abstract
Abstract A surfactant having the capacity of reducing the surface tension in pulmonary alveoli significantly is provided. The surfactant consists essentially of, based on the total weight of the surfactant, 50.6-85.0% of a chlorine phosphogylceride, 4.5-37.6% of an acid phospholipid, 4.6-24.6% of a fatty acid or its analogue and 0.1-10.0% of a lipoprotein derived from the lung of a mammal. These components cooperate to form a kind of film at a gas-liquid interface within pulmonary alveoli and reduce the surface tension. A pharmaceutical composition comprising the surfactant is useable for the clinical treatment of respiratory distress syndrome.
Inventors
- 👤 Tsunetomo Takei
- 👤 Yosaku Kanazawa
- 👤 Kazuo Masuda
- 👤 Yuji Tanaka
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 21:57
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/007; A61K9/0082; A61K38/00; A61K38/16; A61K38/17; A61K38/1703; A61K38/1709; A61K38/395; A61K9/0073; A61P; A61P11/00
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
181 words
A surfactant consisting essentially of (1) a choline phosphoglyceride, (2) an acid phospholipid, (3) a fatty acid or its analogue, and (4) a lipoprotein derived from cattle or pig lungs, the lipoprotein being composed of 47.9 to 70.2%(w/w) of phospholipid part, 23.4 to 48.0%(w/w) of protein part, 1.8 to 5.0%(w/w) of water and 1.4 to 2.4%(w/w) of unknown component parts and having a molecular weight of 30,000 to 38,000, characterized in that the content of the choline phosphoglyceride (1) is 50.6 to 85.0%(w/w), the content of the acid phospholipid (2) is 4.5 to 37.6%(w/w), the content of the fatty acid or its analogue (3) is 4.6 to 24.6%(w/w), the content of the lipoprotein (4) is 0.1 to 10.0%(w/w), all based on the total weight of the surfactant, and characterized in that, when the surfactant is added dropwise to the surface of physiological saline at 37° C. in an amount of 0.8 to 1.5 μg per square centimeter of the surface area, the surfactant gives an equilibrium surface tension of 23.9 to 35.0 dynes/cm in a time of 30 to 100 seconds.
Claim 2
Dependent Claim
181 words
A surfactant consisting essentially of (1) a choline phosphoglyceride, (2) an acid phospholipid, (3) a fatty acid or its analogue, and (4) a lipoprotein derived from cattle or pig lungs, the lipoprotein being composed of 47.9 to 70.2%(w/w) of phospholipid part, 23.4 to 48.0%(w/w) of protein part, 1.8 to 5.0%(w/w) of water and 1.4 to 2.4%(w/w) of unknown component parts and having a molecular weight of 30,000 to 38,000, characterized in that the content of the choline phosphoglyceride (1) is 50.6 to 85.0%(w/w), the content of the acid phospholipid (2) is 4.5 to 37.6%(w/w), the content of the fatty acid or its analogue (3) is 4.6 to 24.6%(w/w), the content of the lipoprotein (4) is 0.1 to 10.0%(w/w), all based on the total weight of the surfactant, and characterized in that, when the surfactant is added dropwise to the surface of physiological saline at 37° C. in an amount of 0.8 to 1.5 μg per square centimeter of the surface area, the surfactant gives an equilibrium surface tension of 23.9 to 35.0 dynes/cm in a time of 30 to 100 seconds.
Claim 3
Dependent Claim
31 words
A surfactant as claimed in claim 1 wherein the lipoprotein has a specific rotatory power [α] D 23 of -40° to -85° at a concentration of 0.1%(w/v) in sodium dodecyl sulfate.
Claim 4
Dependent Claim
45 words
A surfactant as claimed in claim 1 wherein the choline phosphoglyceride is a member selected from the group consisting of a 1,2-diacylglycero-(3)-phosphocholine, a 1-alkyl-2-acylglycero-(3)-phosphocholine, a 1,2-dialkylglycero-(3)-phosphocholine, mixtures of two or more 1,2-diacylglycero-(3)-phosphocholines with two acyl groups having 14 to 24 carbon atoms and mixtures thereof.
Claim 5
Dependent Claim
26 words
A surfactant as claimed in claim 3 wherein the 1,2-diacylglycero-(3)-phosphocholine is a member selected from the group consisting of 1,2-dipalmitoylglycero-(3)-phosphocholine, 1,2-distearoylglycero-(3)-phosphocholine, 1-palmitoyl-2-stearoylglycero-(3)-phosphocholine, 1-stearoyl-2-palmitoylglycero-(3)-phosphocholine and mixtures thereof.
Claim 6
Dependent Claim
22 words
A surfactant as claimed in claim 3 wherein the 1-alkyl-2-acylglycero-(3)-phosphocholine is a member selected from the group consisting of 1-hexadecyl-2-palmitoylglycero-(3)-phosphocholine and 1-octadecyl-2-palmitoylglycero-(3)-phosphocholine.
Claim 7
Dependent Claim
12 words
A surfactant as claimed in claim 3 wherein the 1,2-dialkylglycero-(3)-phosphocholine is 1,2-dihexadecylglycero-(3)-phosphocholine.
Claim 8
Dependent Claim
53 words
A surfactant as claimed in claim 3,4,5 or 6 wherein the optical isomer due to the asymmetric carbon atom at the 2-position of the glycerol residue of the choline phosphoglyceride is a member selected from the group consisting of D-isomer, L-isomer and mixture thereof, when the said choline phosphoglyceride is a simple compound.
Claim 9
Dependent Claim
25 words
A surfactant as claimed in claim 1 wherein the acid phospholipid is a member selected from the group consisting of 1,2-diacyl-sn-glycero-(3)-phosphate, 1,2-diacyl-sn-glycero-(3)-phospho-L-serine, 1,2-diacyl-sn-glycero-(3)-phospho-sn-glycerol and 1,2-diacyl-sn-glycero-(3)-phospho-(1)-L-myoinositol.
Claim 10
Dependent Claim
24 words
A surfactant as claimed in claim 8 wherein the acyl groups are the same or different acyl groups having 14 to 24 carbon atoms.
Claim 11
Dependent Claim
61 words
A surfactant as claimed in claim 1 wherein the fatty acid or its analogue is a member selected from the group consisting of a free fatty acid, an alkali metal salt of a fatty acid, an alkyl ester of a fatty acid, a glyceride of a fatty acid, a fatty acid amide, a fatty alcohol, an aliphatic amine and mixtures thereof.
Claim 12
Dependent Claim
28 words
A surfactant as claimed in claim 10 wherein the free fatty acid is a member selected from the group consisting of palmitic acid, stearic acid and oleic acid.
Claim 13
Dependent Claim
29 words
A surfactant as claimed in claim 10 wherein the alkali metal salt of fatty acid is a member selected from the group consisting of sodium palmitate and sodium stearate.
Claim 14
Dependent Claim
17 words
A surfactant as claimed in claim 10 wherein the alkyl ester of fatty acid is ethyl palmitate.
Claim 15
Dependent Claim
25 words
A surfactant as claimed in claim 10 wherein the glyceride of fatty acid is a member selected from the group consisting of monopalmitin and monostearin.
Claim 16
Dependent Claim
16 words
A surfactant as claimed in claim 10 wherein the fatty acid amide is palmitic acid amide.
Claim 17
Dependent Claim
25 words
A surfactant as claimed in claim 10 wherein the fatty alcohol is a member selected from the group consisting of hexadecyl alcohol and octadecyl alcohol.
Claim 18
Dependent Claim
13 words
A surfactant as claimed in claim 10 wherein the aliphatic amine is hexadecylamine.
Claim 19
Dependent Claim
65 words
A surfactant as claimed in claim 1 wherein the content of phospholipid part is estimated by multiplying its phosphorus content by 25; the content of protein part is expressed in terms of bovine serum albumin; and the content of the unknown component parts is determined by substracting the sum of the phospholipid part, protein part and water contents from the total weight of the lipoprotein.
Claim 20
Dependent Claim
21 words
A surfactant as claimed in claim 1 wherein the molecular weight is measured according to a method based on SDS-gel electrophoresis.
Claim 21
Dependent Claim
42 words
A pharmaceutical composition useable for the treatment of respiratory distress syndrome in adult patients comprising an effective amount of from 400 to 4000 mg of a surfactant as set forth in claim 1 as a unit dosage and a pharmaceutically acceptable carrier.
Claim 22
Dependent Claim
42 words
A pharmaceutical composition useable for the treatment of respiratory distress syndrome in premature infants comprising an effective amount of from 40 to 500 mg of a surfactant as set forth in claim 1 as a unit dosage and a pharmaceutically acceptable carrier.
Claim 23
Dependent Claim
24 words
A pharmaceutical composition as claimed in claim 20 or 21 wherein the carrier is selected from the group consisting of water and physiological saline.
Claim 24
Dependent Claim
19 words
A pharmaceutical composition as claimed in claim 22 wherein the dosage form of the composition is a suspension form.
Claim 25
Dependent Claim
37 words
A method for treating respiratory distress syndrome in adult patients or premature infants comprising instilling or spraying a pharmaceutical composition as set forth in claim 20 or 21 into the airway of the corresponding patient or infant.
Claim 26
Dependent Claim
32 words
A method as claimed in claim 24 wherein, for an adult patient, the treatment is carried out one to ten times within 120 hours before or after the onset of respiratory disturbance.
Claim 27
Dependent Claim
26 words
A method as claimed in claim 24 wherein, for a premature infant, the treatment is carried out one to four times within 72 hours after birth.
References Cited (Backward Citations)
US4338301A
Cited
US4312860A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-07-28 | 1990-01-27 | 1990-07-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-07-28 | 1994-01-27 | 1994-07-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-07-28 | 1998-01-27 | 1998-07-29 | $7700.00 | Window Closed / Lapsed |