Method of preparing total parenteral nutrition solutions

• US 5,278,149 A
• Filed: 01/17/1992
• Issued: 01/11/1994
• Est. Priority Date: 01/17/1992
• Status: Expired due to Fees

• Current Assignee: Beth Israel Deaconess Medical Center, Inc. (Beth Israel Lahey Health, Inc.)
• Original Assignee: New England Deaconess Hospital Corporation
• Inventors: Provost, Pamela S., Driscoll, David F., Bistrian, Bruce R.
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US07/822,526
• Time in Patent Office: 725 Days
• Field of Search: 514/23, 514/938, 514/921, 141/63, 141/114, 210/647, 604/50, 424/450
• US Class Current: 514/23
• CPC Class Codes: A23L 33/17 Amino acids, peptides or proteins
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/295 Iron group metal compounds
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/7004 Monosaccharides having only carbon, hydrogen and oxygen atoms
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof

Abstract

A method of preparing TPN solutions, which is particularly well adaptable to computerized control, has been developed. These methods can assist the pharmacist or physician in the preparation of three-in-one TPN solutions containing lipid, dextrose and amino acids. The method includes a series of criteria for concentrations of lipid, dextrose, amino acids, and ions as well as eliminating the possibility of certain deleterious interactions.

Claims

1. A method of controlling the preparation of a three-in-one total parenteral nutrition solution containing lipid, dextrose, and amino acid components to ensure that said solution meets safety and stability criteria necessary for physiological compatibility and storage requirements comprising the steps of:

1) forming an emulsion of said lipid, said dextrose and said amino acids, the concentrations of each component being selected such that the following tests are met;

a) if straight chain amino acids are used,

space="preserve" listing-type="equation">2%≦

A≦

10%

space="preserve" listing-type="equation">5%≦

D≦

25%

space="preserve" listing-type="equation">2%≦

L≦

6%; and

b) if branched chain amino acids are used,

space="preserve" listing-type="equation">2%≦

A≦

5%

space="preserve" listing-type="equation">5%≦

D≦

15%

space="preserve" listing-type="equation">2%≦

L≦

4%; and

where A is the concentration of amino acids, D is the concentration of dextrose, and L is the concentration of lipid;

2) adding multivalent cations, or their derivatives, in concentrations that do not destabilize said emulsion;

3) adding a salt, if needed, to achieve physiological alkalinization of said emulsion without destabilization, said salt being selected from the group consisting of salts compatible with lipids, steroid drugs and acetate;

4) adding any other ionic materials and drugs to be incorporated in said emulsion in amounts such that the final concentrations in said emulsion do not exceed physiological safety limits;

5) confirming the compatibility of all drugs and additives incorporated into said emulsion; and

6) testing the osmoticity of said emulsion to meet physiologically compatible osmoticity limits.

2. The method of claim 1 wherein said amino acids are solely straight chain amino acids, said adding step comprising adding said amino acids in the form of solution having 3.5-15% amino acids.

3. The method of claim 1 wherein said amino acids comprise branched chain amino acids, said adding step comprising adding branched chain amino acids in the form of solutions having 6.5-8.0% amino acids.

4. The method of claim 1 wherein said adding step comprises adding lipids in the form of emulsions having 10-30% lipids.

5. The method of claim 1 wherein said multivalent cations or their derivatives, are selected from the group consisting of iron ions, iron dextran, calcium ion, zinc ions, calcium gluconate, magnesium ion, and mixtures thereof.

6. The method of claim 1 wherein said step of adding drugs comprises adding drugs selected from the group consisting of steroid drugs, heparin, cimetidine, metoclopramide and mixtures thereof.

7. A computerized method of controlling the preparation of a three-in-one total parenteral nutrition solution containing lipid, dextrose, and amino acid components to ensure that said solution meets safety and stability criteria necessary for physiological compatibility and storage requirements comprising the steps of:

1) generating computer signals to an automatic mixing machine to form an emulsion of said lipid, said dextrose and said amino acids, the concentrations of each component being selected such that the following criteria are met;

a) if straight chain amino acids are used,

space="preserve" listing-type="equation">2%≦

A≦

10

space="preserve" listing-type="equation">5%≦

D≦

25%

space="preserve" listing-type="equation">2≦

L≦

6%; and

b) if branched chain amino acids are used,

space="preserve" listing-type="equation">2%≦

A≦

5%

space="preserve" listing-type="equation">5%≦

D≦

15%

space="preserve" listing-type="equation">2%≦

L≦

4%; and

where A is the final concentration of amino acids, D is the final concentration of dextrose, and L is the final concentration of lipid;

2) generating computer signals to input devices on said mixing machine to control the addition of multivalent cations, or their derivatives, such that said multivalent cations, or their derivatives, are added in concentrations that do not destabilize said emulsion;

3) computer controlling the addition of a selected salt, if needed, to achieve a clinical response from said emulsion, said salt being selected from the group consisting of salts compatible with lipids, steroid drugs and acetate;

4) computer controlling the amounts added of any other ionic materials and drugs to be incorporated in said emulsion such that the final concentrations of said ionic materials and drugs in said emulsion do not exceed physiological safety limits;

5) confirming the compatibility of all drugs and additives to be incorporated into said emulsion; and

6) testing the osmoticity of said emulsion to meet physiologically compatible osmoticity limits.

8. The method of claim 7 wherein said amino acids are solely straight chain amino acids, said adding step comprising adding said amino acids in the form of solutions having 3.5-15% amino acids.

9. The method of claim 7 wherein said amino acids comprise branched chain amino acids, said adding step comprising adding branched chain amino acids in the form of solutions having 6.5-8.0% amino acids.

10. The method of claim 7 wherein said adding step comprises adding lipids in the form of emulsions having 10-30% lipids.

11. The method of claim 7 wherein said multivalent cations or their derivatives, are selected from the group consisting of iron ions, iron dextran, calcium ion, zinc ions, calcium gluconate, magnesium ion, and mixtures thereof.

12. The method of claim 7 wherein said step of adding drugs comprises adding drugs selected from the group consisting of steroid drugs, heparin, cimetidine, metoclopramide and mixtures thereof.