# US 5,703,126 A · Amphiphilic fluorine derivatives with telomeric structures

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 5,703,126 A
- Document ID: US5703126A
- Status: Granted
- Kind: A
- Application number: 08/465,412
- Filed: 1995-06-05
- Granted: 1997-12-30
- Earliest claimed: 1990-08-09
- Assignees: Alliance Pharmaceutical Corp.
- Inventors: Andre A. Pavia; Bernard Pucci; Jean G. Riess; Leila Zarif
- Web page: https://patentgrep.com/patent/US5703126A

## CPC

- A61K 9/0026: {Blood substitute; Oxygen transporting formulations; Plasma extender}
- A61K 8/06: Emulsions
- A61K 8/14: Liposomes; Vesicles
- A61K 8/22: Peroxides; Oxygen; Ozone
- A61K 8/70: containing perfluoro groups, e.g. perfluoroethers
- A61K 8/8158: {Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers}
- A61K 47/54: the modifying agent being an organic compound
- A61K 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine}
- A61K 47/6905: {the form being a colloid or an emulsion}
- A61Q 19/00: Preparations for care of the skin
- C08F 2/38: Polymerisation using regulators, e.g. chain terminating agents {, e.g. telomerisation}
- C08F 20/54: Amides {, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide}
- C08F 20/58: containing oxygen in addition to the carbonamido oxygen {, e.g. N-methylolacrylamide, N-acryloylmorpholine}
- C09K 23/28: Aminocarboxylic acids (proteins and protein hydrolysates C09K23/30)
- C09K 23/38: Alcohols, e.g. oxidation products of paraffins
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C09K: MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE

## Abstract

Fluorinated derivatives useful as surfactants or in the transport of drug or markers, or in drug targeting, and preparations containing the derivatives, for medical, cosmetic and veterinary uses, having the formula: ##STR1## wherein R.sub.F is a fluorinated radical, X is a linear or branched alkylene, R.sup.1 is H or CH.sub.3, R.sup.2 is a radical having at least one OH group, R.sup.3 is a radical derived from an amino acid or a peptide, 1.ltoreq.n.ltoreq.50 and 0.ltoreq.m.ltoreq.200 with 0.2.ltoreq.n/n+m.ltoreq.1. These derivatives can be used as prodrugs or in formulating pharmaceutical, cosmetic and veterinary preparations, in biology and medicine, notably in compositions acting as carriers of oxygen and other gases, of contrast agents, or as carriers of substances used in therapy, or as carriers of markers.

## Claims

### Claim 1

A formulation comprising
a physiologically acceptable carrier; and
a compound of the formula ##STR21## wherein R.sub.F is a C.sub.2 -C.sub.18 fluorinated radical;
X is an C.sub.1 -C.sub.24 alkylene or fluoroalkylene group, linear or branched, having at least one substituent independently selected from the group consisting of --CON(R')--, --SO.sub.2 N(R')--, --S--, --O-- or --N(R')-- wherein R' is H or a C.sub.1 to C.sub.6 alkyl or fluoroalkyl radical; and when X is branched, a part of X can be R.sub.F ;
R.sup.1 is H or CH.sub.3 ;
R.sup.2 is selected from the group consisting of the radicals (CH.sub.2).sub.p --C(CH.sub.2 OH).sub.3, wherein p=0 to 3; Z-R.sub.4, wherein Z is a monovalent or bivalent radical selected from the group consisting of --NH--, --(CH.sub.2).sub.r --N--(R.sup.1)--, --(CH.sub.2).sub.r --O--, or (CH.sub.2).sub.r --S--, wherein r=2 to 4, and R.sup.1 is as defined above; and
R.sup.4 is a monovalent radical derived from an ose, an oside or an amine derivative thereof;
R.sup.3 is an aminoacid residue obtained by removal of a hydrogen atom from the NH.sub.2 group thereof; and
n=1 to 50, provided that R.sup.2 is (CH.sub.2).sub.p --C(CH.sub.2 OH).sub.3 when n=1; and
m=0 or 1 to 200, provided that 0.2.ltoreq.n/n+m.ltoreq.1.

### Claim 2 (depends on 1)

A formulation according to claim 1 wherein said amphiphilic fluorinated compound is bound to a biologically active substance that can serve as a marker.

### Claim 3 (depends on 1, 2)

A formulation according to claim 1 or 2, in the form of a solution, gel, dispersion, liposomal formulation, emulsion, or microemulsion.

### Claim 4 (depends on 3)

The formulation of claim 3, wherein said amphiphilic fluorinated compound is incorporated into lipid vesicles or liposomes comprising natural or synthetic lipids.

### Claim 5 (depends on 1, 2)

A formulation according to claim 1 or 2, suitable for use as a carrier in the transport of gases.

### Claim 6 (depends on 1, 2)

A formulation according to claims 1 or 2, suitable for use as a contrast agent.

### Claim 7 (depends on 1, 2)

A formulation according to claim 1 or 2, suitable for use as a drug, or as a carrier for a drug.

### Claim 8 (depends on 1, 2)

A formulation according to claim 1 or 2, suitable for use as a marker.

### Claim 9 (depends on 1)

A formulation comprising at least one highly fluorinated compound together with at least one amphiphilic fluorinated compound according to claim 1.

### Claim 10 (depends on 9)

A formulation according to claim 9, wherein said highly fluorinated compound is selected from the group consisting of a bis(F-alkyl)-1,2-ethene; an F-isopropyl-1-F-hexyl-2-ethene; a bis(F-hexyl)-1,2-ethene; perfluorodecalin; perfluoromethydecalin; perfluorodimethydecalin; perfluoromethyladamantene or perfluorodimethyladamantene; a perfluorodi- or tri-methylbicyclo(3,3,1)nonane or a homologue thereof; an ether of the formula (CF.sub.3).sub.2 CFO(CF.sub.2 CF.sub.2).sub.2 OCF(CF.sub.3).sub.2 ; (CF.sub.3).sub.2 CFO(CF.sub.2 CF.sub.2).sub.3 OCF(CF.sub.3).sub.2 ; (CF.sub.3).sub.2 CFO(CF.sub.2 CF.sub.2).sub.2 F; (CF.sub.3).sub.2 CFO(CF.sub.2 CF.sub.2).sub.3 F; F(CF(CF.sub.3) CF.sub.2 O).sub.2 CHFCF.sub.3 ; F(CF(CF.sub.3)CF.sub.2 O).sub.3 CHFCF.sub.3, (C.sub.6 F.sub.13).sub.2 O, (C.sub.4 F.sub.9).sub.2 O, an amine selected from the group consisting of N (C.sub.3 F.sub.7).sub.3, a perfluoromethylquinolidine or a perfluoromethylisoquinolidine, a halogenated derivative selected from the group consisting of C.sub.6 F.sub.13 Br, C.sub.6 F.sub.13 CBr.sub.2 CH.sub.2 Br, 1-bromo, 4-perfluoroisopropyl cyclohexane, and .sub.8 F.sub.16 Br.sub.2.

### Claim 11 (depends on 9)

A formulation according to claim 9, wherein said highly fluorinated compound is selected from the group consisting of perfluorodecalin (F-decalin), bis(F-butyl)-1,2-ethene (F-44E) and heptadecafluorobromooctane, C.sub.8 F.sub.17 Br (PFOB).

### Claim 12 (depends on 9)

A formulation according to claim 9, further comprising a fluorinated or hydrocarbonated oil phase in a concentration of from about 10 to 125% w/v, wherein said amphiphilic fluorinated compound is present in a concentration of from about 0.01 to 30% w/v.

### Claim 13 (depends on 9)

A formulation according to claim 9 in the form of an emulsion, a microemulsion or liposomal formulation.