CN105521481A - Parenteral nutritional composition for injection and preparation method thereof - Google Patents
Parenteral nutritional composition for injection and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a medium- and long-chained fat emulsion (OO)/amino acid (16) dipeptide (2)/glucose electrolyte parenteral nutritional composition, containing following ingredients: three cavities of liquid: a first cavity of medium- and long-chained fat emulsion injection (OO) 250 ml; a second cavity of compound amino acid (16) dipeptide (2) injection 500 ml; a third cavity of glucose electrolyte injection 500 ml. The parenteral nutritional composition for injection has the advantage that a formulation of the three cavities and products produced by the preparation process can meet the requirement on all-in-one stability, can also meet the requirements of patients on fat, proteins, carbohydrates and trace elements and are particularly suitable for patients with high catabolism.
Description
Technical field
The present invention relates to medical art, relate to long chain fat emulsion/aminoacid (15) two peptide (2) in one/glucose electrolyte injection parenteral nutrition composition and method of making the same specifically.
Background technology
Parenteral nutrition should with the mode infusion of " All-In-One ".So-called " All-In-One " nutritional solution infusion is by various nutrient substance, and scientifically mixed configuration is in same container to comprise fat milk, aminoacid, glucose and trace element etc., and infusion is to the method for patient simultaneously.In this infusion methods at home and abroad clinical, be proved to be the correct parenteral nutrition infusion of current parenteral nutrition.According to above theory, hospital, when carrying out parenteral nutrition, first should mix various nutrient before infusion, be mixed with total nutrient admixture, then input through vein with the form of mixed liquor, this is the most rational parenteral nutrition implementing measure, good effect, side reaction is few.And total nutrient admixture also brings another benefit, that is exactly that the nutrient mixing rear high concentrations is diluted.The final osmotic pressure of total nutrient admixture is only equivalent to 10% Glucose Liquid, can input through PeV completely, makes Clinical practice more convenient.
Glutamine, a kind of non essential amino acid, plays an important role in many metabolic pathways.It accounts for more than 50% ~ 60% in body free amino acid storehouse, is the precursor substance of nucleic acid and glutathione.Glutamine is the nitrogenous source vehicle in body, and it flows between different organ and tissue, and is called as " the carrying nitrogen car " of transporting fuel, shuttles back and forth in tissue and between small intestine cells, colon cell, lymphocyte and regenerative cell.Remove ammonia metabolic wastes on the one hand, on the other hand for the synthesis of protein and DNA provides nitrogenous source.Glutamine causes intestinal function and immunologic function etc. impaired when lacking, and the ability of particularly defending antibacterial and endotoxin in intestinal to enter portal vein circulation declines.Stress, infect and in the contour catabolic situation of wound, blood plasma and intracellular glutamine concentration decline, body relies on the muscular tissue of decomposing self to produce a large amount of glutamine and utilizes for body.If the glutamine of input external source, the decomposition of muscle can be alleviated, this prognosis to patient and survive relevant.Therefore glutamine is considered to again " conditionally essential amino acid ", namely under normal circumstances, in body, enough glutamine can be synthesized, and at stress state such as heating, wound and operations, in body, synthesis can not meet metabolism needs; If supplement without the external world, the glutamine continued causing body is exhausted and long-term catabolism state.But because glutamine is insoluble in water, and because unstable in aqueous, easily decompose and generate the harmful pyroglutamic acid of body and ammonia.Thus limit its use clinically.
The two peptide formula of amino acid of current Clinical practice, solves critical technological point and the absorption problem that venous transfusion made by glutamine.Glycylglutamine and Glycyl tyrosine naturally dissolve in water, and can tolerate 121 DEG C of heat sterilizations and not decompose, good stability, enter in body and are played a role by being hydrolyzed to rapidly glycine, glutamine and tyrosine.The two peptide of glutamine and tyrosine and Gly-Glu (Gly-Gln) and Gly-Tyr pair peptide (Gly-Tyr), by most clinical trial confirmation safely, effectively, there is vast potential for future development, will play a very important role in surgery and the clinical support of critical nutrition from now on.
In current patent documentation, there is special All-In-One parenteral nutrition three Room bag product composition, as Chinese patent 201410008861.4 " in one long chain fat emulsion/aminoacid (16)/glucose (16%) composition for injection ", Chinese patent 200710020197.5 " composition and method of making the same of the fat milk of packed with three-cavity bag, aminoacid and glucose injection ", Chinese patent 200710020740.1 " composition and method of making the same of the structural fatty milk of packed with three-cavity bag, aminoacid and glucose injection ".Also do not find the All-In-One parenteral nutrition preparation containing glutamine.
Under physical stress state, glutamine is conditionally essential amino acid, is small intestinal mucosa cell sole energy source and the most important nutrient substance of intestinal regeneration.Various wound, hands art, burn, during the stress state such as critical illness disease, body hypermetabolism starts that namely energy demand occurs to be increased, protein synthesis declines, decompose and increase, intestinal mucosa cells, lymphocyte, phagocyte is one of tissue of being exceedingly fast of body renewal speed, a large amount of glutamines is needed during cell regeneration, and now glutamine metabolism and flow abnormalities in body, in body, glutamine is consumed in a large number, blood plasma glutamine concentration is declined, cause the proliferation and function of these fast proliferating cells obviously suppressed, body's immunity declines, exogenous supplementary glutamine can make its plasma concentration recover, thus maintain the normal proliferative of these cells.
Summary of the invention
The object of the present invention is to provide long chain fat emulsion in one (OO)/aminoacid (16) two peptide (2)/glucose electrolyte injection parenteral nutrition compositions, another object of the present invention is to provide the preparation technology of this composition for injection.
The technical solution adopted in the present invention is as follows:
Long chain fat emulsion (OO) in one/aminoacid (16) two peptide (2)/glucose electrolyte parenteral nutrition composition for injection, every bag (1250ml) this parenteral nutrition composition for injection comprises following composition:
Be made up of three Room liquid:
First Room is medium and long chain fat emulsion injection (OO) 250 milliliters, wherein containing olive oil 22.5 ~ 27.5g, median chain triglyceride oil 22.5 ~ 27.5g, glycerol 5.625 ~ 6.875g, Ovum Gallus domesticus Flavus lecithin 2.7 ~ 3.3g, enuatrol 0.0675 ~ 0.0825g;
Second Room is amino acid (16) two peptide (2) injection 500ml, wherein containing alanine 7.2 ~ 8.8g, arginine 5.085 ~ 6.215g, Aspartic Acid 1.53 ~ 1.87g, glutamic acid 2.52 ~ 3.08g, histidine 3.06 ~ 3.74g, isoleucine 2.52 ~ 3.08g, leucine 3.555 ~ 4.345g, lysine acetate 5.715 ~ 6.985g, methionine 2.52 ~ 3.08g, phenylalanine 2.632 ~ 3.218g, proline 3 .06 ~ 3.74g, serine 2.025 ~ 2.475g, threonine 2.52 ~ 3.08g, tryptophan 0.855 ~ 1.045g, valine 3.285 ~ 4.015g, taurine 0.45 ~ 0.55g, one hydration glycylglutamine 13.622 ~ 16.648g, two hydration Glycyl tyrosine 1.552 ~ 1.898g,
3rd Room is glucose electrolyte injection 500ml, wherein containing Dextrose Monohydrate 198.0 ~ 242.0g, sodium chloride 1.053 ~ 1.287g, calcium chloride dihydrate 0.261 ~ 0.319g, magnesium chloride hexahydrate 0.549 ~ 0.671g, zinc chloride 0.005 ~ 0.006g.
On the basis of such scheme, in the first described Room medium and long chain fat emulsion injection, containing the sodium hydroxide that this injection pH value can be adjusted to 8.5 ~ 9.0.
On the basis of such scheme, in the second described Room amino acid (16) two peptide (2) injection, containing the citric acid that this injection pH value can be adjusted to 5.5 ~ 6.0.
The preparation method of long chain fat emulsion (OO) in one/aminoacid (16) two peptide (2)/glucose electrolyte injection parenteral nutrition compositions, comprises following steps:
(1) dosing:
The preparation of a, medium and long chain fat emulsion injection (OO):
Take each component according to quantity, prepare as follows:
Prepared by oil phase: under nitrogen protection, add olive oil, median chain triglyceride oil heating in water bath to 60 ~ 80 DEG C in container, add Ovum Gallus domesticus Flavus lecithin and make it disperse, be prepared into oil phase under 3000 ~ 10000 revs/min of high-speed stirred;
Prepared by aqueous phase: the water of 2/3 volume is heated to 60 ~ 80 DEG C, is placed in container, adds glycerol, enuatrol stirring and evenly mixing through 0.45 μm of membrane filtration, be prepared into aqueous phase.
Prepared by colostrum: in nitrogen protection; under 3000 ~ 20000 revs/min of high-speed stirred, oil phase is poured in aqueous phase and stir 5 ~ 30 minutes, make colostrum, and regulate pH to be 8.5 ~ 9.0 with sodium hydroxide; add water to full dose to stir evenly, be cooled to rapidly 20 ~ 40 DEG C of laggard horizontal high voltages homogeneous.
Homogenizing: under hermetic container and nitrogen protection, moves into two step homogenizer low pressure homogeneous (160/80bar) 10 ~ 30 minutes by obtained colostrum, then through high pressure homogenization (700/80bar) 2 ~ 10 times.Obtain middle long chain fat emulsion (OO) injection.
The preparation of b, amino acid (16) two peptide (2) injection:
Take each component according to quantity, prepare as follows:
Densely to join: in container, add 75 ~ 85 DEG C, the water of 9/20 volume, stir, pass into nitrogen and continue 15 ~ 30 minutes; Drop into leucine, isoleucine, valine; Stir 40 ~ 50 minutes; after dissolving; be cooled to 65 ~ 75 DEG C; drop into alanine, arginine, histidine, Aspartic Acid, methionine, glutamic acid, serine, lysine acetate, threonine, proline, phenylalanine, taurine again; stir 30 ~ 40 minutes; dropping into a hydration glycylglutamine, two hydration Glycyl tyrosines after dissolving, stirring 10 ~ 15 minutes to dissolving.Add 0.05%(W/V-dense part after dissolving to amass) active carbon measured, be incubated 55 ~ 65 DEG C, stir, absorption 15 minutes.Filter carbon removal and be circulated to medicinal liquid clarification;
Rarely to join: stir the clear liquor after dense joining, add tryptophan, stirring and dissolving; Add 45 ~ 55 DEG C of water to full dose, with citric acid adjusted to ph to 5.5 ~ 6.0, continue to pass into nitrogen control dissolved oxygen to 3% ~ 5%(and terminate to fill); Medicinal liquid final temperature 40 ~ 55 DEG C;
The preparation of c, glucose electrolyte injection:
Take each component according to quantity, prepare as follows:
In container, add 50 ~ 60 DEG C, the water of 3/5 volume, add Dextrose Monohydrate, sodium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, zinc chloride successively afterwards, stirring and dissolving; Add 40 ~ 50 DEG C of water to full dose, medicinal liquid final temperature 40 ~ 50 DEG C;
(2) bag-making loading; Long chain fat emulsion (OO) injection, aminoacid (16) two peptide (2) injection, glucose electrolyte injection in preparing are connected on the filling machine of three pipelines and filling element respectively by liquid medicine filter, online bag-making loading, sealing of jumping a queue.
(3) moist heat sterilization: carry out sterilizing immediately after fill, fills nitrogen sterilizing, and shading is protected, sterilizing parameter 115 DEG C ~ 122 DEG C, 8 ~ 30 minutes;
(4) lamp inspection: carry out lamp inspection under 2000 ~ 3000lx light background;
(5) pack: after lamp inspection is qualified, by outer for product high-barrier bag packaging, in the middle of interior outer bag, add a deoxidizer, vacuum nitrogen filling during packaging, after qualified, load corresponding package case.
Advantage of the present invention and effect as follows:
Long chain fat emulsion (OO) in one of the present invention/aminoacid (16) two peptide (2)/glucose electrolyte injection parenteral nutrition compositions wherein Room fat milk contains olive oil and median chain triglyceride oil, can be oxidized fast and effectively and energy is provided, and the immunologic function infringement of soybean oil can be avoided to reduce oxidation risk; Play an important role in many metabolic pathways containing Gly-Glu (Gly-Gln) and two its metabolite glutamine of peptide (Gly-Tyr) of Gly-Tyr in two Room amino acid (16) two peptide (2) injection, there is stronger protective effect containing Mechanisms of Taurine on Cardiaovascular System, and have effects such as strengthening myocardial cell function; Containing trace zinc element in three Room glucose electrolyte injections, be beneficial to patient wound's healing and immunity enhancing that major part accepts parenteral nutrition.According to the product that prescription and the preparation technology of this product three chambers produce, the requirement of All-In-One stability can be met, and the demand of patient to fat, protein, carbohydrate and trace element can be met simultaneously, be particularly useful for the patient of Metabolism.
Detailed description of the invention
The water used in embodiment is fresh water for injection.
Embodiment 1
(1) dosing:
A, medium and long chain fat emulsion injection (OO)
| Composition | Content in every 1000ml |
| Olive oil | 100g |
| Median chain triglyceride oil | 100g |
| Glycerol | 22.5g |
| Ovum Gallus domesticus Flavus lecithin | 12g |
| Enuatrol | 0.3g |
Prepared by oil phase: under nitrogen protection, add recipe quantity olive oil, median chain triglyceride oil, heating in water bath to 70 DEG C in container, add Ovum Gallus domesticus Flavus lecithin and make it disperse, be prepared into oil phase under 8000 revs/min of high-speed stirred.
Prepared by aqueous phase: the water of another 2/3 volume is heated to 75 DEG C, is placed in container, adds glycerol, enuatrol stirring and evenly mixing through 0.45 μm of membrane filtration, be prepared into aqueous phase.
Prepared by colostrum: in nitrogen protection, is poured into by oil phase in aqueous phase and stirs 25 minutes, make colostrum under 10000 revs/min of high-speed stirred, and regulates pH to be 8.5 with sodium hydroxide, adds water to full dose and stirs evenly, be cooled to rapidly 30 DEG C of laggard horizontal high voltages homogeneous.
Homogenizing: under hermetic container and nitrogen protection, moves into two step homogenizer low pressure homogeneous (160/80bar) 20 minutes by obtained colostrum, then through high pressure homogenization (700/80bar) 4 times.Obtain middle long chain fat emulsion (OO) injection.
The preparation of b, amino acid (16) two peptide (2) injection:
| Composition | Content in every 1000ml |
| Alanine | 16.0g |
| Arginine | 11.3g |
| Aspartic Acid | 3.4g |
| Glutamic acid | 5.6g |
| Histidine | 6.8g |
| Isoleucine | 5.6g |
| Leucine | 7.9g |
| Lysine acetate | 12.7g |
| Methionine | 5.6g |
| Phenylalanine | 5.85g |
| Proline | 6.8g |
| Serine | 4.5g |
| Threonine | 5.6g |
| Tryptophan | 1.9g |
| Valine | 7.3g |
| Taurine | 1.0g |
| Glycyl-L-glutamine H 2O | 30.27g |
| Glycyl-L-tyrosine 2H 2O | 3.45g |
Densely to join: in container, add 80 DEG C, the water of 9/20 volume, stir, pass into nitrogen and continue 20 minutes.Drop into leucine, isoleucine, valine; Stir 40 minutes; after dissolving; be cooled to 75 DEG C; drop into alanine, arginine, histidine, Aspartic Acid, methionine, glutamic acid, serine, lysine acetate, threonine, proline, phenylalanine, taurine; stir 40 minutes; dropping into a hydration glycylglutamine, two hydration Glycyl tyrosines after dissolving, stirring 15 minutes to dissolving.Add 0.05%(W/V-dense part after dissolving to amass) active carbon measured, 65 DEG C of insulations, stirring, absorption 15 minutes.Filter carbon removal and be circulated to medicinal liquid clarification.
Rarely to join: stir the clear liquor after dense joining, add tryptophan, stirring and dissolving.Add 45 DEG C of water to full dose, with citric acid adjusted to ph to 5.5, continue to pass into nitrogen control dissolved oxygen and terminate to fill to 5%().Medicinal liquid final temperature 45 DEG C.
The preparation of c, glucose electrolyte injection:
| Composition | Content in every 1000ml |
| Dextrose Monohydrate | 440.0g |
| Sodium chloride | 2.338g |
| Calcium chloride dihydrate | 0.588g |
| Magnesium chloride hexahydrate | 1.22g |
| Zinc chloride | 0.011g |
In container, add 60 DEG C, the water of 3/5 volume, add Dextrose Monohydrate, sodium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, zinc chloride successively afterwards, stirring and dissolving.Add 50 DEG C of water to full dose, medicinal liquid final temperature 50 DEG C.
(2) bag-making loading:
Long chain fat emulsion (OO) injection 250ml, aminoacid (16) two peptide (2) injection 500ml, glucose electrolyte injection 500ml in preparing are connected on the filling machine of three pipelines and filling element respectively by liquid medicine filter, online bag-making loading, sealing of jumping a queue.
(3) moist heat sterilization: carry out sterilizing immediately after fill, fills nitrogen sterilizing, and shading is protected, sterilizing parameter 115 DEG C, 30 minutes.
(4) lamp inspection: lamp inspection after sterilizing.Lamp inspection is carried out under 2000 ~ 3000lx light background.
(5) pack: sample sterilizing lamp inspection immediately after offeing for sale, pack immediately after qualified. by outer for product high-barrier bag packaging, in the middle of interior outer bag, adds a deoxidizer, vacuum nitrogen filling during packaging, after qualified, load corresponding package case.
Embodiment 2:
(1) dosing:
A, medium and long chain fat emulsion injection (OO) 1000ml prepare
Prepared by oil phase: under nitrogen protection, add olive oil 105.0g, median chain triglyceride oil 105.0g, heating in water bath to 80 DEG C in container, add Ovum Gallus domesticus Flavus lecithin 11.0g and make it disperse, be prepared into oil phase under 8000 revs/min of high-speed stirred.
Prepared by aqueous phase: the water of 2/3 volume is heated to 80 DEG C, is placed in container, add glycerol 23.0g, enuatrol 0.35g, stirring and evenly mixing also through 0.45 μm of membrane filtration, is prepared into aqueous phase.
Prepared by colostrum: in nitrogen protection, is poured into by oil phase in aqueous phase and stirs 10 minutes, make colostrum under 20000 revs/min of high-speed stirred, and regulates pH to be 9.0 with sodium hydroxide, adds to the full amount of water for injection and stirs evenly, be cooled to rapidly about 35 DEG C laggard horizontal high voltages homogeneous.
Homogenizing: under hermetic container and nitrogen protection, moves into two step homogenizer low pressure homogeneous (160/80bar) 25 minutes by obtained colostrum, then through high pressure homogenization (700/80bar) 6 times.Obtain middle long chain fat emulsion (OO) injection.
B, amino acid (16) two peptide (2) injection 1000ml prepare:
Densely to join: in container, add 75 DEG C, the water of 9/20 volume, stir, pass into nitrogen and continue 15 minutes.Drop into leucine 7.90g, isoleucine 5.60g, valine 7.30g; Stir 40 minutes; after dissolving; be cooled to 75 DEG C; drop into alanine 16.0g, arginine 11.3g, histidine 6.80g, Aspartic Acid 3.40g, methionine 5.60g, glutamic acid 5.60g, serine 4.50g, lysine acetate 12.7g, threonine 5.60g, proline 6.80g, phenylalanine 5.85g, taurine 1.0g; stir 40 minutes; dropping into glycylglutamine 30.27g, Glycyl tyrosine 3.45g after dissolving, stirring 15 minutes to dissolving.Add 0.05%(W/V-dense part after dissolving to amass) active carbon measured, 65 DEG C of insulations, stirring, absorption 15 minutes.Filter carbon removal and be circulated to medicinal liquid clarification.
Rarely to join: stir the clear liquor after dense joining, add tryptophan 1.90g, stirring and dissolving.Add 45 DEG C of waters for injection to full dose, with citric acid adjusted to ph to 6.0, continue to pass into nitrogen control dissolved oxygen and terminate to fill to 3%().Medicinal liquid final temperature 50 DEG C.Obtain amino acid (16) two peptide (2) injection.
C, glucose electrolyte injection 1000ml prepare:
In container, add 60 DEG C, the water of 3/5 volume, add Dextrose Monohydrate 220.0g, sodium chloride 2.338g, calcium chloride dihydrate 0.588g, magnesium chloride hexahydrate 1.22g, zinc chloride 0.011g, stirring and dissolving.Add 50 DEG C of waters for injection to full dose, medicinal liquid final temperature 50 DEG C.Obtain glucose electrolyte injection.
(2) bag-making loading:
Long chain fat emulsion (OO) injection 250ml, aminoacid (16) two peptide (2) injection 500ml, glucose electrolyte injection 500ml in preparing are connected on the filling machine of three pipelines and filling element respectively by liquid medicine filter, online bag-making loading, sealing of jumping a queue.
(3) moist heat sterilization: should carry out sterilizing immediately after filling, fill nitrogen sterilizing, shading is protected, sterilizing parameter 115 DEG C, 30 minutes.
(4) lamp inspection: lamp inspection after sterilizing.Lamp inspection is carried out under 2000 ~ 3000lx light background.
(5) pack: sample sterilizing lamp inspection immediately after offeing for sale, pack immediately after qualified. by outer for product high-barrier bag packaging, in the middle of interior outer bag, adds a deoxidizer, vacuum nitrogen filling during packaging, after qualified, load corresponding package case.
Embodiment 3:
(1) dosing:
A, medium and long chain fat emulsion injection (OO) 1000ml prepare
Prepared by oil phase: under nitrogen protection, add recipe quantity olive oil 110.0g, median chain triglyceride oil 110.0g, heating in water bath to 65 DEG C in container, add Ovum Gallus domesticus Flavus lecithin 13.0g and make it disperse, be prepared into oil phase under 9000 revs/min of high-speed stirred.
Prepared by aqueous phase: the water of 2/3 volume is heated to 65 DEG C, is placed in container, adds glycerol 23.7g, enuatrol 0.33g stirring and evenly mixing through 0.45 μm of membrane filtration, be prepared into aqueous phase.
Prepared by colostrum: in nitrogen protection, is poured into by oil phase in aqueous phase and stirs 30 minutes, make colostrum under 15000 revs/min of high-speed stirred, and regulates pH to be 8.7 with sodium hydroxide, adds to the full amount of water for injection and stirs evenly, be cooled to rapidly about 25 DEG C laggard horizontal high voltages homogeneous.
Homogenizing: under hermetic container and nitrogen protection, moves into two step homogenizer low pressure homogeneous (160/80bar) 15 minutes by obtained colostrum, then through high pressure homogenization (700/80bar) 8 times.Obtain middle long chain fat emulsion (OO) injection.
B, amino acid (16) two peptide (2) injection 1000ml prepare:
Densely to join: in container, add 83 DEG C, the water of 45% volume, stir, pass into nitrogen and continue 30 minutes.Drop into leucine 8.20g, isoleucine 6.10g, valine 8.00g; Stir 50 minutes; after dissolving; be cooled to 70 DEG C; drop into alanine 17.0g, arginine 12.0g, histidine 7.40g, Aspartic Acid 3.70g, methionine 6.10g, glutamic acid 6.10g, serine 4.90g, lysine acetate 13.90g, threonine 6.10g, proline 7.40g, phenylalanine 6.40g, taurine 1.1g; stir 35 minutes; dropping into glycylglutamine 33.0g, Glycyl tyrosine 3.70g after dissolving, stirring 13 minutes to dissolving.Add 0.05%(W/V-dense part after dissolving to amass) active carbon measured, 60 DEG C of insulations, stirring, absorption 15 minutes.Filter carbon removal and be circulated to medicinal liquid clarification.
Rarely to join: stir above-mentioned clear liquor, add tryptophan 2.00g, stirring and dissolving.Add 50 DEG C of waters for injection to full dose, with citric acid adjusted to ph to 5.8, continue to pass into nitrogen control dissolved oxygen and terminate to fill to 4%().Medicinal liquid final temperature 50 DEG C.Obtain amino acid (16) two peptide (2) injection.
C, glucose electrolyte injection 1000ml prepare:
In container, add 60 DEG C, the water of 60% volume, add Dextrose Monohydrate 480.0g, sodium chloride 2.500g, calcium chloride dihydrate 0.630g, magnesium chloride hexahydrate 1.300g, zinc chloride 0.010g, stirring and dissolving.Add 40 DEG C of waters for injection to full dose, medicinal liquid final temperature 40 DEG C.Obtain glucose electrolyte injection.
(2) bag-making loading:
Long chain fat emulsion (OO) injection 250ml, aminoacid (16) two peptide (2) injection 500ml, glucose electrolyte injection 500ml in preparing are connected on the filling machine of three pipelines and filling element respectively by liquid medicine filter, online bag-making loading, sealing of jumping a queue.
(3) moist heat sterilization: should carry out sterilizing immediately after filling, fill nitrogen sterilizing, shading is protected, sterilizing parameter 121 DEG C, 15 minutes.
(4) lamp inspection: lamp inspection after sterilizing.Lamp inspection is carried out under 2000 ~ 3000lx light background.
(5) pack: sample sterilizing lamp inspection immediately after offeing for sale, pack immediately after qualified. by outer for product high-barrier bag packaging, in the middle of interior outer bag, adds a deoxidizer, vacuum nitrogen filling during packaging, after qualified, load corresponding package case.
Embodiment 4:
(1) dosing:
A, medium and long chain fat emulsion injection (OO) 1000ml prepare:
Prepared by oil phase: under nitrogen protection, add recipe quantity olive oil 95.0g, median chain triglyceride oil 95.0g, heating in water bath to 78 DEG C in container, add Ovum Gallus domesticus Flavus lecithin 10.8g and make it disperse, be prepared into oil phase under 5000 revs/min of high-speed stirred.
Prepared by aqueous phase: the water of 2/3 volume is heated to 72 DEG C, is placed in container, adds glycerol 25.0g, enuatrol 0.30g stirring and evenly mixing through 0.45 μm of membrane filtration, be prepared into aqueous phase.
Prepared by colostrum: in nitrogen protection, is poured into by oil phase in aqueous phase and stirs 27 minutes, make colostrum under 18000 revs/min of high-speed stirred, and regulates pH to be 8.6 with sodium hydroxide, adds to the full amount of water for injection and stirs evenly, be cooled to rapidly about 30 DEG C laggard horizontal high voltages homogeneous.
Homogenizing: under hermetic container and nitrogen protection, moves into two step homogenizer low pressure homogeneous (160/80bar) 30 minutes by obtained colostrum, then through high pressure homogenization (700/80bar) 10 times.Obtain middle long chain fat emulsion (OO) injection.
B, amino acid (16) two peptide (2) injection 1000ml prepare:
Densely to join: in dense dispensing container, add 77 DEG C, the water of 45% volume, open and stir, pass into nitrogen and continue 23 minutes.Drop into leucine 8.50g, isoleucine 5.50g, valine 7.50g; Stir 43 minutes; after dissolving; be cooled to 68 DEG C; drop into alanine 15.0g, arginine 11.5g, histidine 7.20g, Aspartic Acid 3.20g, methionine 5.50g, glutamic acid 5.50g, serine 4.20g, lysine acetate 12.5g, threonine 5.50g, proline 6.50g, phenylalanine 5.50g, taurine 1.0g; stir 40 minutes; dropping into glycylglutamine 28.2g, Glycyl tyrosine 3.60g after dissolving, stirring 14 minutes to dissolving.Add 0.05%(W/V-dense part after dissolving to amass) active carbon measured, 55 DEG C of insulations, stirring, absorption 15 minutes.Filter carbon removal and be circulated to medicinal liquid clarification.
Rarely to join: stir clarification medicinal liquid, add tryptophan 1.80g, stirring and dissolving.Add 50 DEG C of water to full dose, with citric acid adjusted to ph to 5.9, continue to pass into nitrogen control dissolved oxygen and terminate to fill to 5%().Medicinal liquid final temperature 50 DEG C.Obtain amino acid (16) two peptide (2) injection.
C, glucose electrolyte injection 1000ml prepare:
In container, add 53 DEG C, the water of 60% volume, add Dextrose Monohydrate 470.0g, sodium chloride 2.422g, calcium chloride dihydrate 0.550g, magnesium chloride hexahydrate 1.120g, zinc chloride 0.011g, stirring and dissolving.Add 50 DEG C of waters for injection to full dose, medicinal liquid final temperature 50 DEG C.Obtain glucose electrolyte injection.
(2) bag-making loading:
Long chain fat emulsion (OO) injection 250ml, aminoacid (16) two peptide (2) injection 500ml, glucose electrolyte injection 500ml in preparing are connected on the filling machine of three pipelines and filling element respectively by liquid medicine filter, online bag-making loading, sealing of jumping a queue.
(3) moist heat sterilization: should carry out sterilizing immediately after filling, fill nitrogen sterilizing, shading is protected, sterilizing parameter 121 DEG C, 30 minutes.
(4) lamp inspection: lamp inspection after sterilizing.Lamp inspection is carried out under 2000 ~ 3000lx light background.
(5) pack: sample sterilizing lamp inspection immediately after offeing for sale, pack immediately after qualified. by outer for product high-barrier bag packaging, in the middle of interior outer bag, adds a deoxidizer, vacuum nitrogen filling during packaging, after qualified, load corresponding package case.
Above-described embodiment is illustrative instead of determinate, can list several embodiments, therefore in the change do not departed under general plotting of the present invention and amendment, should belong within protection scope of the present invention according to institute's limited range.
Claims (4)
1. long chain fat emulsion (OO) in/aminoacid (16) two peptide (2)/glucose electrolyte parenteral nutrition composition for injection, it is characterized in that, every bag of parenteral nutrition composition for injection, comprises following composition:
Be made up of three Room liquid:
First Room is medium and long chain fat emulsion injection (OO) 250 milliliters, wherein containing olive oil 22.5 ~ 27.5g, median chain triglyceride oil 22.5 ~ 27.5g, glycerol 5.625 ~ 6.875g, Ovum Gallus domesticus Flavus lecithin 2.7 ~ 3.3g, enuatrol 0.0675 ~ 0.0825g;
Second Room is amino acid (16) two peptide (2) injection 500ml, wherein containing alanine 7.2 ~ 8.8g, arginine 5.085 ~ 6.215g, Aspartic Acid 1.53 ~ 1.87g, glutamic acid 2.52 ~ 3.08g, histidine 3.06 ~ 3.74g, isoleucine 2.52 ~ 3.08g, leucine 3.555 ~ 4.345g, lysine acetate 5.715 ~ 6.985g, methionine 2.52 ~ 3.08g, phenylalanine 2.632 ~ 3.218g, proline 3 .06 ~ 3.74g, serine 2.025 ~ 2.475g, threonine 2.52 ~ 3.08g, tryptophan 0.855 ~ 1.045g, valine 3.285 ~ 4.015g, taurine 0.45 ~ 0.55g, one hydration glycylglutamine 13.622 ~ 16.648g, two hydration Glycyl tyrosine 1.552 ~ 1.898g,
3rd Room is glucose electrolyte injection 500ml, wherein containing Dextrose Monohydrate 198.0 ~ 242.0g, sodium chloride 1.053 ~ 1.287g, calcium chloride dihydrate 0.261 ~ 0.319g, magnesium chloride hexahydrate 0.549 ~ 0.671g, zinc chloride 0.005 ~ 0.006g.
2. long chain fat emulsion (OO) in one according to claim 1/aminoacid (16) two peptide (2)/glucose electrolyte injection parenteral nutrition compositions, it is characterized in that, in the first described Room medium and long chain fat emulsion injection, containing the sodium hydroxide that this injection pH value can be adjusted to 8.5 ~ 9.0.
3. long chain fat emulsion (OO) in one according to claim 2/aminoacid (16) two peptide (2)/glucose electrolyte injection parenteral nutrition compositions, it is characterized in that, in the second described Room amino acid (16) two peptide (2) injection, containing the citric acid that this injection pH value can be adjusted to 5.5 ~ 6.0.
4. a preparation method for long chain fat emulsion (OO) in the one according to any one of claim 1-3/aminoacid (16) two peptide (2)/glucose electrolyte injection parenteral nutrition compositions, is characterized in that: comprise following steps:
(1) dosing:
The preparation of a, medium and long chain fat emulsion injection (OO):
Take each component according to quantity, prepare as follows:
Prepared by oil phase: under nitrogen protection, add olive oil, median chain triglyceride oil heating in water bath to 60 ~ 80 DEG C in container, add Ovum Gallus domesticus Flavus lecithin and make it disperse, be prepared into oil phase under 3000 ~ 10000 revs/min of high-speed stirred;
Prepared by aqueous phase: the water of 2/3 volume is heated to 60 ~ 80 DEG C, is placed in container, adds glycerol, enuatrol stirring and evenly mixing through 0.45 μm of membrane filtration, be prepared into aqueous phase;
Prepared by colostrum: in nitrogen protection, under 3000 ~ 20000 revs/min of high-speed stirred, oil phase is poured in aqueous phase and stir 5 ~ 30 minutes, make colostrum, and regulate pH to be 8.5 ~ 9.0 with sodium hydroxide, add water to full dose to stir evenly, be cooled to rapidly 20 ~ 40 DEG C of laggard horizontal high voltages homogeneous;
Homogenizing: under hermetic container and nitrogen protection, moves into two step homogenizer low pressure homogeneous (160/80bar) 10 ~ 30 minutes by obtained colostrum, then through high pressure homogenization 700/80bar, 2 ~ 10 times, obtains middle long chain fat emulsion (OO) injection;
The preparation of b, amino acid (16) two peptide (2) injection:
Take each component according to quantity, prepare as follows:
Densely to join: in container, add 75 ~ 85 DEG C, the water of 9/20 volume, stir, pass into nitrogen and continue 15 ~ 30 minutes; Drop into leucine, isoleucine, valine; Stir 40 ~ 50 minutes, after dissolving, be cooled to 65 ~ 75 DEG C, drop into alanine, arginine, histidine, Aspartic Acid, methionine, glutamic acid, serine, lysine acetate, threonine, proline, phenylalanine, taurine again, stir 30 ~ 40 minutes, dropping into a hydration glycylglutamine, two hydration Glycyl tyrosines after dissolving, stirring 10 ~ 15 minutes to dissolving; Add 0.05%(W/V-dense part after dissolving to amass) active carbon measured, be incubated 55 ~ 65 DEG C, stir, absorption 15 minutes, filter carbon removal and be circulated to medicinal liquid clarification;
Rarely to join: stir the clear liquor after dense joining, add tryptophan, stirring and dissolving; Add 45 ~ 55 DEG C of water to full dose, with citric acid adjusted to ph to 5.5 ~ 6.0, continue to pass into nitrogen and control dissolved oxygen to 3% ~ 5%, terminate to fill; Medicinal liquid final temperature 40 ~ 55 DEG C;
The preparation of c, glucose electrolyte injection:
Take each component according to quantity, prepare as follows:
In container, add 50 ~ 60 DEG C, the water of 3/5 volume, add Dextrose Monohydrate, sodium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, zinc chloride successively afterwards, stirring and dissolving; Add 40 ~ 50 DEG C of water to full dose, medicinal liquid final temperature 40 ~ 50 DEG C;
(2) bag-making loading; Long chain fat emulsion (OO) injection, aminoacid (16) two peptide (2) injection, glucose electrolyte injection in preparing are connected on the filling machine of three pipelines and filling element respectively by liquid medicine filter, online bag-making loading, sealing of jumping a queue;
(3) moist heat sterilization: carry out sterilizing immediately after fill, fills nitrogen sterilizing, and shading is protected, sterilizing parameter 115 DEG C ~ 122 DEG C, 8 ~ 30 minutes;
(4) lamp inspection: carry out lamp inspection under 2000 ~ 3000lx light background;
(5) pack: after lamp inspection is qualified, by outer for product high-barrier bag packaging, in the middle of interior outer bag, add a deoxidizer, vacuum nitrogen filling during packaging, after qualified, load corresponding package case.
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