Claims
- 1. An adjuvant composition comprising:
- (a) an immunopotentiating amount of an immunostimulating glycopeptide, wherein said glycopeptide is a compound of the formula ##STR4## wherein R and R.sup.1 are the same or different and are hydrogen or acyl containing from 1 to 22 carbon atoms;
- R.sup.2 is an unsubstituted or substituted alkyl radical containing from 1 to 22 carbon atoms, or a unsubstituted or substituted aryl radical containing from 6 to 10 carbon atoms;
- R.sup.3 is hydrogen, alkyl, or aryl of 7 to 10 carbon atoms;
- R.sup.4 is hydrogen or alkyl;
- X is an aminoacyl moiety selected from the group consisting of alanyl, valyl, leucyl, isoleucyl, .alpha.-aminobutyryl, threonyl, methionyl, cysteinyl, glutamyl, glutaminyl, aspartyl, phenylalanyl, tyrosyl, tryptophanyl, lysyl, ornithinyl, arginyl, histidyl, asparginyl, prolyl, hydroxyprolyl, seryl, or glycyl;
- R.sup.5 and R.sup.6 are the same or different and are a carboxyl group, a carboxyl group esterified with a lower alkanol, or a carbamoyl group, which, on the nitrogen atom, is unsubstituted or mono-substituted or di-substituted by alkyl, aryl, aralkyl, alkylidene, or carbamoylmethyl;
- (b) a multi-phase-forming amount between 0.2 and 49% by volume (v/v) of a non-toxic polyoxypropylene-polyoxyethylene block polymer, wherein said block polymer is liquid over a temperature range between about 15.degree.-40.degree. C., has a polyoxypropylene base of molecular weight between 2250 and 4300, and has polyoxyethylene in an amount between 1 and 30% of the block polymer;
- (c) a multi-phase-stabilizing amount between 0.05 and 2.5% by volume (v/v) of a glycol ether-based surfactant; and
- (d) buffered isoosmotic saline in a quantity sufficient to make volume.
- 2. The composition of claim 1 wherein said glycopeptide is present in an amount between 0.01 to 2% by weight/volume.
- 3. An adjuvant composition comprising:
- (a) an immunopotentiating amount of an immunostimulating glycopeptide, wherein said glycopeptide is a compound of the formula ##STR5## wherein R and R.sup.1 are the same or different and are hydrogen or acyl containing from 1 to 22 carbon atoms;
- R.sup.2 is unsubstituted or substituted alkyl radical containing from 1 to 22 carbon atoms, or an unsubstituted or substituted aryl radical containing from 6 to 10 carbon atoms;
- R.sup.3 is hydrogen, alkyl, or aryl of 7 to 10 carbon atoms;
- R.sup.4 is hydrogen or alkyl;
- X is an aminoacyl moiety selected from the group consisting of alanyl, valyl, leucyl, isoleucyl, .alpha.-aminobutyryl, threonyl, methionyl, cysteinyl, glutamyl, glutaminyl, aspartyl, phenylalanyl, tyrosyl, tryptophanyl, lysyl, ornithinyl, arginyl, histidyl, asparginyl, prolyl, hydroxyprolyl, seryl, or glycyl;
- R.sup.5 and R.sup.6 are the same or different and are a carboxyl group, a carboxyl group esterified with a lower alkanol, or a carbamoyl group, which, on the nitrogen atom, is unsubstituted or mono-substituted or di-substituted by alkyl, aryl, aralkyl, alkylidene, or carbamoylmethyl;
- (b) a multi-phase-forming amount between 0.2 and 49% by volume (v/v) of a non-toxic polyoxypropylene-polyoxyethylene block polymer, wherein said block polymer is liquid over a temperature range between about 15.degree.-40.degree. C., has a polyoxypropylene base of molecular weight between 2250 and 4300, and has polyoxyethylene in an amount between 1 and 30% of the block polymer;
- (c) a multi-phase-stabilizing amount between 0.05 and 2.5% by volume (v/v) of a glycol ether-based surfactant;
- (d) a metabolizable, non-toxic oil in an amount between 1 to 30% by volume (v/v); and
- (e) buffered isoosmotic saline in a quantity sufficient to make volume.
- 4. The composition of claim 3 wherein said glycopeptide is present in an amount between 0.01 to 2% by weight/volume.
- 5. The composition of claim 2 wherein said block polymer is comprised of a polyoxypropylene base of molecular weight between 3,250 and 4,000 and polyoxyethylene in an amount between 0.2 and 20% of said block polymer; and
- said saline is phosphate buffered saline.
- 6. The composition of claim 5 wherein the glycopeptide is a compound of Formula (I) wherein
- R and R.sup.1 are the same or different and are selected from the group consisting of hydrogen or an acyl radical containing from 1 to 22 carbon atoms;
- R.sup.2 is methyl;
- R.sup.3 is hydrogen;
- X is present in an amount between 0.01 and 1% (w/v) and is an aminoacyl moiety selected from the group consisting of L-seryl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, L-.alpha.-aminobutyryl, L-threonyl, L-methionyl, L-cysteinyl, L-phenylalanyl, L-tyrosyl, L-tryptophanyl, L-lysyl, L-ornithyl, L-arginyl, L-histidyl, L-glutamyl, L-glutaminyl, L-aspartyl, L-asparaginyl, L-prolyl, or L-hydroxyprolyl;
- said block polymer is prsent in an amount between 0.2 and 20% (v/v) and is comprised of polyoxypropylene base of molecular weight between 2,750 and 3,550 and polyoxyethylene in an amount between 5 and 20% of said block polymer; and
- said glycol ether-based surfactant is a polysorbate surfactant present in an amount between 0.2 and 1% (v/v).
- 7. The composition of claim 6 wherein said glycopeptide is a compound of Formula (I) wherein
- R, R.sup.1 and R.sup.3 are hydrogen;
- R.sup.2 is methyl;
- R.sup.4 is methyl or hydrogen;
- X is L-valyl, L-alanyl, L-seryl, L-threonyl or L-.alpha.-aminobutyryl;
- R.sup.5 is carboxyl, carbamoyl or n-butyl carboxylate; and
- R.sup.6 is carboxyl or carbamoyl.
- 8. The composition of claim 7 wherein said glycopeptide is N-acetylmuramyl-L-threonyl-D-isoglutamine, N-acetyl-L-.alpha.-aminobutyryl-D-isoglutamine, 6-O-stearoyl-N-acetylmuramyl-L-.alpha.-aminobutyryl-D-isoglutamine, or N-acetyldesmethylmuramyl-L-alanyl-D-isoglutamine present in an amount between 0.01 to 1% (w/v);
- said block polymer is present in an amount between 0.2 and 5% (v/v) and is comprised of a polyoxypropylene base of molecular weight 3250 and polyoxyethylene in an amount of 10% of said block polymer; and
- said polysorbate surfactant is polyoxyethylene 20 sorbitan monooleate.
- 9. The composition of claim 7 wherein said glycopeptide is n-butyl-N-acetylmuramyl-L-alanyl-D-glutaminate, N-acetylmuramyl-L-alanyl-D-isoglutamine, or N-acetylmuramyl-L-seryl-D-isoglutamine; and
- said block polymer is comprised of a polyoxypropylene base of molecular weight 3250 and polyoxyethylene in an amount of 10% of said block polymer.
- 10. The composition of claim 8 wherein said glycopeptide is N-acetylmuramyl-L-threonyl-D-isoglutamine present in an amount of 0.5% (w/v), and said block polymer is present in an amount of 2.5% (v/v).
- 11. The composition of claim 4 wherein said block polymer is comprised of a polyoxypropylene base of molecular weight between 3,250 and 4,000 and polyoxyethylene in an amount between about 0.2 and 20% of said block polymer; and
- said saline is phosphate buffered saline.
- 12. The composition of claim 11 wherein the glycopeptide of Formula (I) wherein
- R and R.sup.1 are the same or different and are selected from the group consisting of hydrogen or an acyl radical containing from 1 to 22 carbon atoms;
- R.sup.2 is methyl;
- R.sup.3 is hydrogen;
- X is present in an amount between 0.01 and 1% (w/v) and is an aminoacyl moiety selected from the group consisting of L-seryl, L-alanyl, L-valyl, L-leucyl, L-isoleucyl, L-.alpha.-aminobutyryl, L-threonyl, L-methionyl, L-cysteinyl, L-phenylalanyl, L-tyrosyl, L-tryptophanyl, L-lysyl, L-ornithyl, L-arginyl, L-histidyl, L-glutamyl, L-glutaminyl, L-aspartyl, L-asparaginyl, L-prolyl, or L-hydroxyprolyl;
- said block polymer is present in an amount between 0.2 and 20% (v/v) and is comprised of polyoxypropylene base of molecular weight between 2,750 and 3,550 and polyoxyethylene in an amount between 5 and 20% of said block polymer; and
- said glycol ether-based surfactant is a polysorbate surfactant present in an amount between 0.2 and 1% (v/v).
- 13. The composition of claim 12 wherein said glycopeptide is a compound of Formula (I) wherein
- R, R.sup.1 and R.sup.3 are hydrogen;
- R.sup.2 is methyl;
- R.sup.4 is methyl or hydrogen;
- X is L-valyl, L-alanyl, L-seryl, L-threonyl or L-.alpha.-aminobutyryl;
- R.sup.5 is carboxyl, carbamoyl or n-butyl carboxylate; and
- R.sup.6 is carboxyl or carbamoyl.
- 14. The composition of claim 13 wherein said glycopeptide is N-acetylmuramyl-L-threonyl-D-isoglutamine, N-acetyl-L-.alpha.-aminobutyryl-D-isoglutamine, 6-O-stearoyl-N-acetylmuramyl-L-.alpha.-aminobutyryl-D-isoglutamine, or N-acetyldesmethylmuramyl-L-alanyl-D-isoglutamine present in an amount between 0.01 and 1% (w/v);
- said block polymer is present in an amount between 0.2 and 5% (v/v) and is comprised of a polyoxypropylene base of molecular weight 3250 and polyoxyethylene in an amount of 10% of said block polymer; and
- said polysorbate surfactant is polyoxyethylene 20 sorbitan monooleate.
- 15. The composition of claim 13 wherein said glycopeptide is n-butyl-N-acetylmuramyl-L-alanyl-D-glutaminate, N-acetylmuramyl-L-alanyl-D-isoglutamine, or N-acetylmuramyl-L-seryl-D-isoglutamine; and
- said block polymer is comprised of a polyoxypropylene base of molecular weight 3250 and polyoxyethylene in an amount of 10% of said block polymer.
- 16. A composition according to claim 8 wherein said glycopeptide is N-acetylmuramyl-L-threonyl-D-isoglutamine present in an amount of 0.5% (w/v), and said block polymer is present in an amount of 2.5% (v/v).
Parent Case Info
This is a division of pending application Ser. No. 525,190, filed Aug. 22, 1983, now U.S. Pat. No. 4,606,918 incorporated herein by reference.
US Referenced Citations (24)
Foreign Referenced Citations (1)
Number |
Date |
Country |
3308458-A |
Sep 1984 |
DEX |
Non-Patent Literature Citations (4)
Entry |
Dukor et al, Annual Reports in Medicinal Chemistry-14, Chapter 15 (Immunostimulants) pp. 1416-1467. |
Hunter, et al., J. Immunol., 127, 1244 (1981). |
Hunter, et al., Rev. Cancer Res., 3, 279-286 (1980). |
Snippe, et al., Int. Archs. Allergy Appl. Immun., 65, 390-398 (1981). |
Divisions (1)
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Number |
Date |
Country |
Parent |
525190 |
Aug 1983 |
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