1. A composition comprising:
an effective disinfecting amount of stearyl dihydroxypropyldimonium oligosaccharide in an ophthalmically acceptable aqueous solution.
2. The composition of claim 1 wherein said effective disinfecting amount is about 0.0001 to about 10 weight percent.
3. The composition of claim 1 further comprising one or more aminoalcohol buffers and one or more tonicity agents.
4. The composition of claim 3 wherein said one or more aminoalcohol buffers
are selected from the group consisting of monoethanolamine, diethanolamine, triethanolamine, 2-amino-2-methyl-1,3-propanediol, 2-dimethylamino-2-methyl-1-propanediol, 2-amino-2-ethylpropanol, 2-amino-1-butanol and 2-amino-2-methyl-1-propanol.
5. The composition of claim 3 wherein said one or more aminoalcohol buffers
are present in about 0.02 to about 3.0 percent by weight.
6. The composition of claim 3 wherein said one or more tonicity agents are
selected from the group consisting of sodium chloride, potassium chloride, dextrose, mannose, glycerin, calcium chloride and magnesium chloride.
7. The composition of claim 3 wherein said one or more tonicity agents are
present in about 0.01 to about 3.0 percent by weight.
8. The composition of claim 3 wherein said one or more tonicity agents are
present in an amount to provide a final osmotic value of about 200 to about 450 mOsmkg.
9. A method of producing the composition of claim 1 comprising:
combining an effective disinfecting amount of stearyl dihydroxypropyldimonium oligosaccharide with water to form a solution, wherein the solution is ophthalmically safe.
10. The method of claim 9 wherein said effective disinfecting amount is about 0.0001 to about 10 weight percent.
11. The method of claim 9 further comprising one or more aminoalcohol buffers and one or more tonicity agents.
12. The method of claim 9 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more aminoalcohol buffers are selected from the group consisting of monoethanolamine, diethanolamine, triethanolamine, 2-amino-2-methyl-1,3-propanediol, 2-dimethylamino-2-methyl-1-propanediol, 2-amino-2-ethylpropanol, 2-amino-1-butanol and 2-amino-2-methyl-1-propanol.
13. The method of claim 9 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more aminoalcohol buffers are present in about 0.02 to about 3.0 percent by weight.
14. The method of claim 9 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more tonicity agents are selected from the group consisting of sodium chloride, potassium chloride, dextrose, mannose, glycerin, calcium chloride and magnesium chloride.
15. The method of claim 9 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more tonicity agents are present in about 0.01 to about 3.0 percent by weight.
16. The method of claim 9 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more tonicity agents are present in an amount to provide a final osmotic value of about 200 to about 450 mOsmkg.
17. The method of claim 9 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein an additional buffer or buffering system is present.
18. A solution comprising an amount of stearyl dihydroxypropyldimonium oligosaccharide and water wherein the solution is ophthalmically safe.
19. The solution of claim 18 wherein said effective disinfecting amount is about 0.0001 to about 10 weight percent.
20. The solution of claim 18 further comprising one or more aminoalcohol buffers and one or more tonicity agents.
21. The solution of claim 18 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more aminoalcohol buffers are selected from the group consisting of monoethanolamine, diethanolamine, triethanolamine, 2-amino-2-methyl-1,3-propanediol, 2-dimethylamino-2-methyl-1-propanediol, 2-amino-2-ethylpropanol, 2-amino-1-butanol and 2-amino-2-methyl-1-propanol.
22. The solution of claim 18 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more aminoalcohol buffers are present in about 0.02 to about 3.0 percent by weight.
23. The solution of claim 18 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more tonicity agents are selected from the group consisting of sodium chloride, potassium chloride, dextrose, mannose, glycerin, calcium chloride and magnesium chloride.
24. The solution of claim 18 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more tonicity agents are present in about 0.01 to about 3.0 percent by weight.
25. The solution of claim 18 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein said one or more tonicity agents are present in an amount to provide a final osmotic value of about 200 to about 450 mOsmkg.
26. The solution of claim 18 further comprising one or more aminoalcohol buffers and one or more tonicity agents wherein an additional buffer or buffering system is present.
27. A method of desinfecting a contact lens comprising:
contacting a contact lens with an ophthalmically safe aqueous solution comprising dihydroxypropyldimonium oligosaccharide for a period of time suitable to reduce or eliminate a microbial burden on said contact lens.
28. A composition for treating a contact lens comprising:
an effective amount of dihydroxypropyldimonium oligosaccharide in an ophthalmically safe aqueous solution.
29. The composition of claim 28 wherein said effective amount is about 0.0001 to about 10 weight percent.
30. A composition for disinfecting a contact lens comprising:
a disinfecting amount of dihydroxypropyldimonium oligosaccharide in an ophthalmically safe aqueous solution.
31. The composition of claim 30 wherein said disinfecting amount is about 0.0001 to about 10 weight percent.
32. A composition for preserving a contact lens comprising:
a preservative amount of dihydroxypropyldimonium oligosaccharide in an ophthalmically safe aqueous solution.
33. The composition of claim 32 wherein said preservative amount is about 0.0001 to about 10 weight percent.
34. The composition of claim 28, 30 or 32 further comprising one or more aminoalcohol buffers and one or more tonicity agents.
35. The composition of claim 28, 30 or 32 further comprising one or more aminoalcohol buffers selected from the group consisting of monoethanolamine, diethanolamine, triethanolamine, 2-amino-2-methyl-1,3-propanediol, 2-dimethylamino-2-methyl-1-propanediol, 2-amino-2-ethylpropanol, 2-amino-1-butanol and 2-amino-2-methyl-1-propanol.
36. The composition of claim 28, 30 or 32 further comprising one or more aminoalcohol buffers present in about 0.02 to about 3.0 percent by weight.
37. The composition of claim 28, 30 or 32 further comprising one or more tonicity agents selected from the group consisting of sodium chloride, potassium chloride, dextrose, mannose, glycerin, calcium chloride and magnesium chloride.
38. The composition of claim 28, 30 or 32 further comprising one or more tonicity agents present in about 0.01 to about 3.0 percent by weight.
39. The composition of claim 28, 30 or 32 further comprising one or more tonicity agents present in an amount to provide a final osmotic value of about 200 to about 450 mOsmkg.
40. The composition of claim 28, 30 or 32 further comprising a buffer or buffering system.
The claims below are in addition to those above.
All refrences to claims which appear below refer to the numbering after this setence.
The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
1. A method for determining the absolute rate of bone resorption, which comprises quantitating the concentration of peptide fragments in a body fluid, the peptide fragments being derived from bone collagen resorption and having a 3-hydroxypyridinium cross-link.
2. The method of claim 1, wherein the 3-hydroxypyridinium cross-link is lysyl pyridinoline.
3. The method of claim 1, wherein the 3-hydroxypyridinium cross-link is hydroxylysyl pyridinoline.
4. The method of claim 1, wherein the body fluid is urine.
5. The method of claim 1, wherein the quantitating step comprises contacting the body fluid with an immunological binding partner specific to a peptide fragment having a 3-hydroxypyridinium cross-link derived from bone collagen resorption.
6. The method of claim 5, further comprising, prior to the contacting step, purifying the body fluid.
7. The method of claim 6, wherein the purifying step comprises a procedure selected from the group consisting of cartridge adsorption and elution, molecular sieve chromatography, dialysis, ion exchange, alumina chromatography, and hydroxyapatite chromatography.
8. The method of claim 1, wherein the quantitating step comprises those selected from the group consisting of ultraviolet absorbance spectroscopy, natural fluorescence spectroscopy and electrochemical titration.
9. The method of claim 1, wherein the quantitating step comprises electrochemical titration.
10. The method of claim 9, further comprising prior to the electro-chemical titration step, purifying the body fluid.
11. The method of claim 10, wherein the purifying step comprises a procedure selected from the group consisting of dialysis, ion exchange chromatography, alumina chromatography, molecular sieve chromatography, and hydroxyapatite chromatography.
12. The method of claim 10, wherein the purifying step comprises adsorbing the body fluid on an ion-exchange adsorption filter, eluting the ion-exchange adsorption filter and collecting the eluate containing peptide fragments having a 3-hydroxypyridinium cross-link.
13. The method of claim 10, further comprising, after purifying the body fluid, resolving the peptide fragments having a 3-hydroxypyridinium cross-link.
14. The method of claim 1, wherein the quantitating step comprises fluorometric measurement.
15. The method of claim 14, further comprising, prior to the fluorometric measurement step, purifying the body fluid.
16. The method of claim 15, further comprising, after purifying the body fluid, hydrolyzing the peptide fragments thereby forming a hydrolyzate.
17. The method of claim 16, comprising, after hydrolyzing the peptide fragments, resolving the hydrolyzate.
18. The method of claim 17, wherein the resolving step comprises chromatographic resolution.
19. The method of claim 18, wherein the chromatographic resolution step comprises high performance liquid chromatography.
20. The method of claim 15, wherein the purifying step comprises:
(a) dialyzing an aliquot of urine against an aqueous buffered solution, thereby producing a partially purified peptide fragment containing non-diffusate,
(b) lyophilizing the non-diffusate,
(c) dissolving the lyophilized non-diffusate in an ion pairing solution,
(d) adsorbing the non-diffusate onto an affinity chromatography column,
(e) washing the adsorbed non-diffusate with a volume of ion pairing solution, and
(f) eluting the affinity column containing the peptide fragments with an eluting solution.
21. The method of claim 20, further comprising the step, prior to adsorbing the non-diffusate, contacting the non-diffusate with a molecular sieving column.
22. A peptide fragment derived from bone collagen and obtained from a body fluid, substantially free of other human peptides.
23. The peptide fragment of claim 22, containing a 3-hydroxypyridinium cross-link.
24. The peptide fragment of claim 22, containing a lysyl pyridinoline cross-link.
25. The peptide fragment of claim 22, containing a hydroxylysyl pyridinoline cross-link.
26. The peptide fragment of claim 22, comprising an amino acid sequence that derives from the aminoterminal telopeptide domain of bone type I collagen linked through a 3-hydroxypyridinium cross-link, the peptide fragment having an amino acid composition (Asx)2-(Glx)2-(Gly)5-Val-Tyr-Ser-Thr and having one residue of hydroxylysyl pyridinoline or lysyl pyridinoline.
where
Asx is the amino acid Asp or Asn, and
Glx is the amino acid Glu or Gln.
27. The peptide fragment of claim 22, comprising the amino acid sequence:
6
is hydroxylysyl pyridinoline or lysyl pyridinoline, and
Gln is glutamine or wholly cyclized pyrrolidone carboxylic acid.
28. The peptide fragment of claim 22, comprising an amino acid sequence that derives from the carboxyterminal telopeptide domain of bone type I collagen.
29. The peptide fragment of claim 28, wherein the amino acid sequence contains a lysyl pyridinoline cross-link.
30. The peptide fragment of claim 28, wherein the amino acid sequence contains a hydroxylysyl pyridinoline cross-link.
31. The peptide fragment of claim 28, comprising the amino acid sequence:
7
is hydroxylysyl pyridinoline or lysyl pyridinoline.
32. The peptide fragment of claim 22, wherein the body fluid is selected from the group consisting of urine, synovial fluid, and serum.
33. The peptide fragment of claim 32, wherein the body fluid is urine.
34. A fused cell hybrid which produces monoclonal antibodies specific for the peptide fragment of claim 22.
35. A monoclonal antibody produced by the fused cell hybrid of claim 34.
36. The monoclonal antibody of claim 35, coupled to a detectable marker.
37. The monoclonal antibody of claim 36, wherein the detectable marker is selected from the group consisting of enzymes, chromophores, fluorophores, coenzymes, enzyme inhibitors, chemiluminescent materials, paramagnetic metals, spin labels, and radionuclides.
38. A test kit for quantitating the amount of peptide fragments in a body fluid, the peptide fragment being derived from bone collagen resorption and having a 3-hydroxypyridinium cross-link, comprising the monoclonal antibody of claim 35.
39. The test kit of claim 38, wherein the monoclonal antibody is coupled to a detectable marker.