Ready-to-use parenteral nutrition formulation
The present disclosure relates to a terminally heat-sterilized ready-to-use parenteral nutrition formulation comprising all macronutrients and micronutrients required to meet the clinical guidelines for parenteral nutrition, wherein all said micronutrients and macronutrients are provided in one multi-chamber bag (MCB). The disclosure is also directed to a parenteral nutrition formulation comprising all such macronutrients and micronutrients. More specifically, the present disclosure is directed to a MCB comprising at least five chambers containing a carbohydrate formulation in a first chamber, an amino acid formulation in a second chamber, a lipid formulation in a third chamber, a fourth chamber comprising a vitamin formulation and a fifth chamber comprising a trace element formulation, wherein the carbohydrate formulation, amino acid formulation and/or the lipid formulation may also contain certain vitamins and certain trace elements that can be stably accommodated therein.
1 . A terminally heat-sterilized multi-chamber container comprising at least:
(a) a first chamber comprising a carbohydrate formulation and vitamins;
(b) a second chamber comprising an amino acid formulation and vitamins, wherein the vitamins in the second chamber comprise at least one of vitamin B8 or vitamin B9;
(c) a third chamber comprising a lipid formulation;
(d) a fourth chamber comprising a trace element formulation; and
(e) a fifth chamber comprising a vitamin formulation,
wherein the vitamin formulation of the fifth chamber is a lipid emulsion having a pH of from 5.0 to 7.0, and comprises vitamin B12, vitamin B2, vitamin B5, vitamin A and optionally further comprises vitamin D, vitamin E, and/or vitamin K, wherein the trace element formulation comprises at least selenium (Se), wherein the terminally heat-sterilized multi-chamber container was sterilized at a temperature of 121° C. for at least 8 minutes, and wherein the vitamin formulation does not comprise glucose, does not comprise vitamin B1, and does not comprise vitamin C.
2 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the trace element formulation further comprises zinc (Zn), copper (Cu) and manganese (Mn).
3 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the multi-chamber container further comprises at least one electrolyte selected from the group of electrolytes consisting of sodium (Na + ), chloride (Cl − ), potassium (K + ), magnesium (Mg 2+ ), calcium (Ca 2+ ), hydrogen phosphate (HPO 4 − ), glycerophosphate (C 3 H 7 O 6 P 2− ), acetate (CH 3 COO − ) and hydrogen carbonate (HCO 3 − ).
4 . The terminally heat-sterilized multi-chamber container of claim 3 , wherein the at least one electrolyte is provided in the amino acid formulation.
5 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the carbohydrate formulation or the trace element formulation comprises calcium.
6 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the carbohydrate formulation comprises glucose and at least one vitamin selected from the group of vitamins consisting of vitamin B1, vitamin B3 and vitamin B6.
7 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the carbohydrate formulation is an aqueous solution having a pH of from 3.2 to 5.5 and comprises
(a) from 24 g to 411 g glucose,
(b) from 0.1 g to 1.5 g calcium,
(c) from 1.1 mg to 10.0 mg vitamin B1,
(d) from 16 mg to 115 mg vitamin B3, and
(e) from 0.5 mg to 10.5 mg vitamin B6.
8 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the vitamins in the second chamber further comprise vitamin C.
9 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the amino acid formulation is an aqueous solution having a pH of from 4.5 to 7.0, and comprises:
(a) from 8 g to 223 g amino acids,
(b) from 17 μg to 125 μg vitamin B8,
(c) from 120 μg to 1000 μg vitamin B9,
(d) from 60 mg to 340 mg vitamin C, and
(e) optionally one or more electrolytes selected from the group consisting of sodium, potassium, glycerophosphate, magnesium, calcium, acetate, and chloride.
10 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the trace element formulation is an aqueous solution having a pH of from 2.0 to 4.0 and comprises:
(a) from 580 μg to 7000 μg zinc,
(b) from 10 μg to 120 μg selenium,
(c) from 80 μg to 800 μg copper,
(d) from 1 μg to 350 μg manganese, and optionally
(e) from 0 μg to 3000 μg iron,
(f) from 0 μg to 25 μg chromium,
(g) from 5 μg to 200 μg iodine,
(h) from 0 μg to 1500 μg fluorine, and/or
(i) from 1 μg to 30 μg molybdenum.
11 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the trace element formulation further comprises an organic acid selected from the group of organic acids consisting of malic acid, tartaric acid, citric acid, maleic acid, and fumaric acid in a concentration of from 50 mM to 400 mM.
12 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the vitamin formulation comprises:
(a) from 0.5 mg to 6.0 mg vitamin B2,
(b) from 4.3 mg to 45.0 mg vitamin B5, and
(c) from 0.7 μg to 35.0 μg vitamin B12.
13 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the vitamin formulation comprises vitamin A, vitamin D, vitamin K and vitamin E.
14 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the vitamin formulation comprises an aqueous phase, and 1% to 20% by weight of an oil phase based on the total weight of the lipid emulsion.
15 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the vitamin formulation contains no more than 1.5 ppm of dissolved oxygen.
16 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the multi-chamber container comprises a sixth chamber comprising:
(a) a lipid emulsion having a pH of from 5.0 to 9.0 which comprises an aqueous phase and 1% to 20% by weight of an oil phase based on the total weight of the lipid emulsion, and contains less than 1.5 ppm of dissolved oxygen,
(b) vitamin A, and
(c) optionally at least one of the vitamins selected from the group of vitamins consisting of vitamin D, vitamin K and vitamin E.
17 . The terminally heat-sterilized multi-chamber container of claim 16 , wherein the vitamin formulation of the fifth chamber further comprises less than 1.5 ppm dissolved oxygen.
18 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the lipid formulation comprises an aqueous phase and about 5% to about 35% by weight of an oil phase.
19 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the lipid formulation comprises vitamin A and optionally at least one vitamin selected from the group of vitamins consisting of vitamin D, vitamin K and vitamin E.
20 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the vitamin formulation comprises fat-soluble vitamins and the fat-soluble vitamins are present in an amount of
(a) from 215 IU to 6600 IU vitamin A,
(b) from 400 IU to 1700 IU vitamin D,
(c) from 8 IU to 40 IU vitamin E, and
(d) from 30 μg to 650 μg vitamin K, respectively.
21 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the multi-chamber container is terminally heat-sterilized by moist heat.
22 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the chambers of the multi-chamber container are separated from each other by non-permanent seals.
23 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the fourth and fifth chambers, and optionally a sixth chamber each have a volume of from 2.5 mL to 50 mL.
24 . The terminally heat-sterilized multi-chamber container of claim 1 , wherein the formulations of the at least five chambers can be reconstituted by breaking non-permanent seals separating the chambers from each other.
25 . The terminally heat-sterilized multi-chamber container of claim 1 for providing parenteral nutrition to a patient when oral or enteral nutrition is impossible, insufficient, or contraindicated.
26 . The terminally heat-sterilized multi-chamber container according to claim 25 , wherein the patient is an adult patient.
27 . The terminally heat-sterilized multi-chamber container according to claim 1 for providing total parenteral nutrition (TPN) or partial parenteral nutrition (PPN).
28 . The terminally heat-sterilized multi-chamber container according to claim 1 for providing total parenteral nutrition (TPN) or partial parenteral nutrition (PPN) to home parenteral nutrition (HPN) patients.
29 . The terminally heat-sterilized multi-chamber container of claim 9 , wherein the pH of the amino acid formulation is from 6.0 to 7.0.