CN105079010A - Medicine composition of compound amino acid injection 18AA and application - Google Patents

Abstract

The invention provides a novel medicine composition of compound amino acid injection (18AA). The medicine composition has the advantages that the medicine composition can be applied to preparing medicine which are used for certain patients, can improve nutritional statuses of postoperative patients and can prevent or treat metabolic acidosis and the like, body metabolic requirements of the certain patients cannot be met by amino acid in the certain patients with deficiency of protein intake, absorption obstacle and the like, and accordingly the obtained medicine composition can be clinically used for novel intended population or is high in pertinence and clinical safety when clinically used.

Description

The pharmaceutical composition of Amino Acid Compound Injection 18AA and purposes

Technical field

The present invention relates to medical art, be specifically provided for the patient that the aminoacid such as protein Deficiency of Intake, malabsorption can not meet organism metabolism needs.Also for improving pharmaceutical composition and its preparation and the purposes of the Amino Acid Compound Injection (18AA) of the effects such as the nutriture of patients after surgery.Product of the present invention be more adapted to metabolic acidosis or high chlorine type metabolic acidosis etc. need the patient of supplementary 18AA amino acid injection under many diseases or symptom, product of the present invention has safety or more widely or the indication upgraded or adaptation population etc. on Clinical practice.

Background technology

Protein forms cyto-architectural main component, the elementary cell of protein structure is aminoacid, human body needs to take in a certain amount of protein to meet the needs of vital movement every day, when q.s cannot be taken in by gastrointestinal tract because of certain reason, just must input Freamine Ⅲ from vein and be supplemented.The control of proteinaceous nutrient to disease is significant, and particularly at surgical wound or postoperative, in patient's body, breaks down proteins or metabolism sharply increase, and occur negative nitrogen balance very soon, and the state of an illness is worsened further.It is reported in inpatient's death, have the immediate cause of 10 ~ 30% death or main cause to be malnutrition by title.Due to the use of intravenous hyperalimentation agent, many salvage grave patients are pulled through.At present, the intravenous hyperalimentation agent used clinically mainly contains hydrolyzed protein and aminoacids complex transfusion.Amino Acid Compound Injection containing 18 seed amino acids is very important amino acid supplements, plays an important role clinically.Amino Acid Compound Injection (18AA) is as Branchamin (Chinese Pharmacopoeia 2010 editions the second enlarged editions, p270), for protein Deficiency of Intake, the aminoacid such as malabsorption can not meet the patient of organism metabolism needs, also for improving the nutriture of patients after surgery, but existing preparation may cause acid base imbalance or other untoward reaction or indication to be restricted in certain situation input body, unexpected bad problem etc. is there is after causing some diseases not use or to use, or the clinical selectivity to this medicine maybe this kind of medicine is restricted, it is made to become pharmaceutics or pharmacology or and the focus of related discipline research or the object of research.

Summary of the invention

Existing Amino Acid Compound Injection (18AA) is not suitable for the patient of high chlorine type metabolic acidosis in other instances.Patients with Big Area Burn often mostly occurs high sodium, chloremia, during treatment burn patient, in acute stage or critical phase, for saving the life of patient, need can adopt amino acid transfusion during rapid supply nutrition, with the rapid recovery of the every function of gastrointestinal function and health ensureing patient.For above-mentioned patient, or occur that the symptom of patient of above-mentioned disease may not easily judge clinically, (18AA may increase the weight of the state of an illness or occur serious life danger input Amino Acid Compound Injection, this irrational situation is turned a blind eye to for a long time, this that is Amino Acid Compound Injection (18AA) there is serious defect.For example, set forth from the angle of philosophy, even if the high blood pressure disease that the common people generally know, the novel antihypertensive medicament not only having the common people in its medicine but also have medical worker not for knowing, the nineties Chinese Clinical pharmacy or medical expert more be do not approve of the different combination antihypertensives giving fixed dosage clinically to treat serious high blood pressure disease, the exploitation of past Chinese antihypertensive drug be perhaps dynamically the refraction of this situation.In logic, we also find the defect of other medicines or the not enough or part that haves much room for improvement for similar or broad sense.We find, comprise and under easily there is the multiple various disease situations such as metabolic acidosis, to inject existing Amino Acid Compound Injection (18AA) also not enough or the unsatisfactory or hidden danger that exists in various degree of existing defects, when life-and-death matter or more and more focus on individual character treatment, this reduces the safety of medication and convenience or adaptability to a great extent, therefore, we through research be the clinical pharmaceutical composition that new novel compound amino acid injection (18AA) is provided, the preparation of new pharmaceutical composition is provided, the drug combination preparation that the new existing preparation of ratio is more excellent is provided, not only reduce the untoward reaction of different situations, improve clinical therapeutic efficacy, new selection is provided for clinical, and meet clinical needs in varied situations.

The pharmaceutical composition of new Amino Acid Compound Injection 18AA of the present invention, is characterized in that: in every 1000ml solution containing principal agent component be:

Pharmaceutical composition 1: in every 1000ml solution containing principal agent component be:

Proline or L-PROLINE 0.80-1.20 gram;

Serine or Serine 0.80-1.20 gram;

Alanine or ALANINE 1.60-2.40 gram;

Isoleucine or ILE 2.816-4.23 gram;

Leucine or L-Leu 3.92-5.88 gram;

Aspartic Acid or L-ASPARTIC ACID 2.00-3.00 gram;

Tyrosine or TYR 0.20-0.30 gram;

Glutamic acid or Pidolidone 0.60-0.90 gram;

Phenylalanine or L-Phe 4.26-6.40 gram;

Arginine or L-arginine 3.31-4.96 gram, or Arginine acetate. or L-Arginine acetate. 4.45-6.68 gram;

Lysine acetate 3.89-5.83 gram or lysine 2.76-4.14 gram, or L-lysine acetate 3.89-5.83 gram or or 1B 2.76-4.14 gram;

Valine or Valine 2.88-4.32 gram;

Threonine or L-threonine 2.00-3.00 gram;

Histidine or L-Histidine 1.48-2.23 gram;

Tryptophan or L-Trp 0.72-0.96 gram;

Methionine or METHIONINE 1.80-2.70 gram;

Cystine or CYSTINE 0.08-0.12 gram;

Glycine 6.08-9.12 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Separately can contain adjuvant antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant or stabilizing agent 0-8.0 gram;

Or pharmaceutical composition 2: or in every 1000ml solution containing principal agent component be:

Proline or L-PROLINE 0.80-1.20 gram;

Serine or Serine 0.80-1.20 gram;

Alanine or ALANINE 1.60-2.40 gram;

Isoleucine or ILE 2.816-4.23 gram;

Leucine or L-Leu 3.92-5.88 gram;

Aspartic Acid or L-ASPARTIC ACID 2.00-3.00 gram;

Tyrosine or TYR 0.20-0.30 gram;

Glutamic acid or Pidolidone 0.60-0.90 gram;

Phenylalanine or L-Phe 4.26-6.40 gram;

Arginine or L-arginine 3.31-4.96 gram, or Arginine acetate. or L-Arginine acetate. 4.45-6.68 gram;

Lysine acetate 3.89-5.83 gram, or lysine 2.76-4.14 gram, or L-lysine acetate 3.89-5.83 gram or 1B 2.76-4.14 gram, or lysine hydrochloride or LYS 3.44-5.16 gram;

Valine or Valine 2.88-4.32 gram;

Threonine or L-threonine 2.00-3.00 gram;

Histidine hydrochloride or L-Histidine hydrochlorate (C ₆h ₉n ₃o ₂hClH ₂o) 2.00-3.00 gram;

Tryptophan or L-Trp 0.72-1.08 gram;

Methionine or METHIONINE 1.80-2.70 gram;

Cystine or CYSTINE 0.08-0.12 gram;

Glycine 6.08-9.12 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Separately can contain adjuvant antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant or stabilizing agent 0-8.0 gram;

Or pharmaceutical composition 3: or in every 1000ml solution containing principal agent component be:

Proline or L-PROLINE 0.80-1.20 gram;

Serine or Serine 0.80-1.20 gram;

Alanine or ALANINE 1.60-2.40 gram;

Isoleucine or ILE 2.816-4.23 gram;

Leucine or L-Leu 3.92-5.88 gram;

Aspartic Acid or L-ASPARTIC ACID 2.00-3.00 gram;

Tyrosine or TYR 0.20-0.30 gram;

Glutamic acid or Pidolidone 0.60-0.90 gram;

Phenylalanine or L-Phe 4.26-6.40 gram;

Arginine hydrochloride or L-arginine hydrochloride 4.00-6.00 gram;

Lysine acetate 3.89-5.83 gram, or lysine 2.76-4.14 gram, or L-lysine acetate 3.89-5.83 gram or 1B 2.76-4.14 gram;

Valine or Valine 2.88-4.32 gram;

Threonine or L-threonine 2.00-3.00 gram;

Histidine hydrochloride or L-Histidine hydrochlorate (C ₆h ₉n ₃o ₂hClH ₂o) 2.00-3.00 gram;

Tryptophan or L-Trp 0.72-1.08 gram;

Methionine or METHIONINE 1.80-2.70 gram;

Cystine or CYSTINE 0.08-0.12 gram;

Glycine 6.08-9.12 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Separately can contain adjuvant antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant or stabilizing agent 0-8.0 gram;

Or pharmaceutical composition 4: in every 1000ml solution containing principal agent component be:

Proline or L-PROLINE 0.80-1.20 gram;

Serine or Serine 0.80-1.20 gram;

Alanine or ALANINE 1.60-2.40 gram;

Isoleucine or ILE 2.816-4.23 gram;

Leucine or L-Leu 3.92-5.88 gram;

Aspartic Acid or L-ASPARTIC ACID 2.00-3.00 gram;

Tyrosine or TYR 0.20-0.30 gram;

Glutamic acid or Pidolidone 0.60-0.90 gram;

Phenylalanine or L-Phe 4.26-6.40 gram;

Arginine hydrochloride or L-arginine hydrochloride 4.00-6.00 gram;

Lysine acetate 3.89-5.83 gram, or lysine 2.76-4.14 gram, or L-lysine acetate 3.89-5.83 gram or 1B 2.76-4.14 gram;

Valine or Valine 2.88-4.32 gram;

Threonine or L-threonine 2.00-3.00 gram;

Histidine or L-Histidine 1.48-2.22 gram;

Tryptophan or L-Trp 0.72-1.08 gram;

Methionine or METHIONINE 1.80-2.70 gram;

Cystine or CYSTINE 0.08-0.12 gram;

Glycine 6.08-9.12 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Separately can contain adjuvant antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant or stabilizing agent 0-8.0 gram;

Or pharmaceutical composition 5:12% content, in every 1000ml solution containing principal agent component be:

Proline or L-PROLINE 1.92-2.88 gram;

Serine or Serine 1.92-2.88 gram;

Alanine or ALANINE 3.84-5.76 gram;

Isoleucine or ILE 6.76-10.14 gram;

Leucine or L-Leu 9.408-14.12 gram;

Aspartic Acid or L-ASPARTIC ACID 4.80-7.20 gram;

Tyrosine or TYR 0.48-0.72 gram;

Glutamic acid or Pidolidone 1.44-2.16 gram;

Phenylalanine or L-Phe 10.24-15.36 gram;

Arginine or L-arginine 7.938-11.91 gram, or Arginine acetate. or L-Arginine acetate. 10.67-16.02 gram;

Lysine acetate 9.32-14.00 gram or lysine 6.61-9.92 gram, or L-lysine acetate 9.32-14.00 gram or 1B 6.61-9.92 gram;

Valine or Valine 6.91-10.37 gram;

Threonine or L-threonine 4.80-7.20 gram;

Histidine or L-Histidine 3.55-5.33 gram, or histidine hydrochloride or L-Histidine hydrochlorate 4.80-7.20 gram;

Tryptophan or L-Trp 1.73-2.60 gram;

Methionine or METHIONINE 4.32-6.48 gram;

Cystine or CYSTINE 0.19-0.29 gram;

Glycine 14.59-21.89 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Separately can contain adjuvant antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant or stabilizing agent 0-8.0 gram;

Or pharmaceutical composition 6: in every 1000ml solution containing principal agent component be:

Proline or L-PROLINE 1.92-2.88 gram;

Serine or Serine 1.92-2.88 gram;

Alanine or ALANINE 3.84-5.76 gram;

Isoleucine or ILE 6.76-10.14 gram;

Leucine or L-Leu 9.408-14.12 gram;

Aspartic Acid or L-ASPARTIC ACID 4.80-7.20 gram;

Tyrosine or TYR 0.48-0.72 gram;

Glutamic acid or Pidolidone 1.44-2.16 gram;

Phenylalanine or L-Phe 10.24-15.36 gram;

Arginine hydrochloride or L-arginine hydrochloride 9.60-14.40 gram;

Lysine acetate 9.33-14.00 gram or lysine 6.61-9.92 gram, or L-lysine acetate 9.33-14.00 gram or 1B 6.61-9.92 gram;

Valine or Valine 6.92-10.37 gram;

Threonine or L-threonine 4.80-7.20 gram;

Histidine or L-Histidine 3.55-5.33 gram, or histidine hydrochloride or L-Histidine hydrochlorate 4.80-7.20 gram;

Tryptophan or L-Trp 1.73-2.60 gram;

Methionine or METHIONINE 4.32-6.48 gram;

Cystine or CYSTINE 0.19-0.29 gram;

Glycine 14.59-21.89 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Separately can contain adjuvant antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant or stabilizing agent 0-8.0 gram;

Or pharmaceutical composition 7: in every 1000ml solution containing principal agent component be:

Proline or L-PROLINE 1.92-2.88 gram;

Serine or Serine 1.92-2.88 gram;

Alanine or ALANINE 3.84-5.76 gram;

Isoleucine or ILE 6.76-10.14 gram;

Leucine or L-Leu 9.408-14.12 gram;

Aspartic Acid or L-ASPARTIC ACID 4.80-7.20 gram;

Tyrosine or TYR 0.48-0.72 gram;

Glutamic acid or Pidolidone 1.44-2.16 gram;

Phenylalanine or L-Phe 10.24-15.36 gram

Arginine hydrochloride or L-arginine hydrochloride 9.60-14.4 gram;

Lysine hydrochloride or LYS 8.26-12.39 gram;

Valine or Valine 6.92-10.37 gram;

Threonine or L-threonine 4.80-7.20 gram;

Histidine or L-Histidine 3.55-5.33 gram;

Tryptophan or L-Trp 1.73-2.60 gram;

Methionine or METHIONINE 4.32-6.48 gram;

Cystine or CYSTINE 0.19-0.29 gram;

Glycine 14.59-21.89 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Separately can contain adjuvant antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant or stabilizing agent 0-8.0 gram;

The pharmaceutical composition of Amino Acid Compound Injection 18AA of the present invention is more preferably as follows,

Pharmaceutical composition 8, in every 1000ml aqueous solution containing principal agent component is:

Proline or L-PROLINE 1.00 grams;

Serine or Serine 1.00 grams;

Alanine or ALANINE 2.00 grams;

Isoleucine or ILE 3.52 grams;

Leucine or L-Leu 4.90 grams;

Aspartic Acid or L-ASPARTIC ACID 2.50 grams;

Tyrosine or TYR 0.25 gram;

Glutamic acid or Pidolidone 0.75 gram;

Phenylalanine or L-Phe 5.33 grams;

Arginine or L-arginine 4.135 grams, or Arginine acetate. or L-Arginine acetate. 5.56 grams;

Lysine acetate or L-lysine acetate 4.855 grams, or lysine or 1B 3.45g;

Valine or Valine 3.60 grams;

Threonine or L-threonine 2.50 grams;

Histidine or L-Histidine 1.85 grams;

Tryptophan or L-Trp 0.90 gram;

Methionine or METHIONINE 2.25 grams;

Cystine or CYSTINE 0.10 gram;

Glycine 7.60 grams;

Sorbitol or xylitol or 50.00 grams, mannitol;

Separately can contain adjuvant antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant 0.01-3.0g gram;

Or pharmaceutical composition 9, in every 1000ml aqueous solution containing component be:

Proline or L-PROLINE 1.00 grams;

Serine or Serine 1.00 grams;

Alanine or ALANINE 2.00 grams;

Isoleucine or ILE 3.52 grams;

Leucine or L-Leu 4.90 grams;

Aspartic Acid or L-ASPARTIC ACID 2.50 grams;

Tyrosine or TYR 0.25 gram;

Glutamic acid or Pidolidone 0.75 gram;

Phenylalanine or L-Phe 5.33 grams;

Arginine or L-arginine 4.135 grams, or Arginine acetate. or L-Arginine acetate. 5.56 grams;

Lysine acetate or L-lysine acetate 4.86 grams, or lysine or 1B 3.45g;

Valine or Valine 3.60 grams;

Threonine or L-threonine 2.50 grams;

Histidine hydrochloride or L-Histidine hydrochlorate 2.50g gram;

Tryptophan or L-Trp 0.90 gram;

Methionine or METHIONINE 2.25 grams;

Cystine or CYSTINE 0.10 gram;

Glycine 7.60 grams;

Sorbitol or xylitol or 50.00 grams, mannitol;

Separately adjuvant can be contained, pharmaceutically acceptable antioxidant or stabilizing agent 0.01-3.0g gram;

Or compositions 10, in every 1000ml aqueous solution containing principal agent component be:

Proline or L-PROLINE 2.40 grams;

Serine or Serine 2.40 grams;

Alanine or ALANINE 4.80 grams;

Isoleucine or ILE 8.45 grams;

Leucine or L-Leu 11.76 grams;

Aspartic Acid or L-ASPARTIC ACID 6.00 grams;

Tyrosine or TYR 0.60 gram;

Glutamic acid or Pidolidone 1.80 grams;

Phenylalanine or L-Phe 12.80 grams;

Arginine hydrochloride or L-arginine hydrochloride 12.00 grams;

Lysine acetate 11.65 grams or lysine 8.26 grams, or L-lysine acetate 11.65 grams or 1B 8.26 grams;

Valine or Valine 8.64 grams;

Threonine or L-threonine 6.00 grams;

Histidine or L-Histidine 4.44 grams, or histidine hydrochloride or L-Histidine hydrochlorate 6.00 grams;

Tryptophan or L-Trp 2.16 grams;

Methionine or METHIONINE 5.40 grams;

Cystine or CYSTINE 0.24 gram;

Glycine 18.24 grams;

Sorbitol or xylitol or mannitol or xylose or glucose or 50 grams, fructose;

Separately adjuvant can be contained, pharmaceutically acceptable antioxidant or stabilizing agent 0.01-3.0g gram;

Or compositions 11, in every 1000ml aqueous solution containing principal agent component be:

Proline or L-PROLINE 2.40 grams;

Serine or Serine 2.40 grams;

Alanine or ALANINE 4.80 grams;

Isoleucine or ILE 8.45 grams;

Leucine or L-Leu 11.76 grams;

Aspartic Acid or L-ASPARTIC ACID 6.00 grams;

Tyrosine or TYR 0.60 gram;

Glutamic acid or Pidolidone 1.80 grams;

Phenylalanine or L-Phe 12.80 grams;

Arginine or L-arginine 4.135 grams, or Arginine acetate. or L-Arginine acetate. 5.56 grams;

Lysine acetate 11.65 grams or lysine 8.26 grams, or L-lysine acetate 11.65 grams or 1B 8.26 grams;

Valine or Valine 8.64 grams;

Threonine or L-threonine 6.00 grams;

Histidine or L-Histidine 4.44 grams, or histidine hydrochloride or L-Histidine hydrochlorate 6.00 grams;

Tryptophan or L-Trp 2.16 grams;

Methionine or METHIONINE 5.40 grams;

Cystine or CYSTINE 0.24 gram;

Glycine 18.24 grams;

Sorbitol or xylitol or 50 grams, mannitol;

In pharmaceutical composition of the present invention, the type of service of different component can be different, as: histidine hydrochloride or L-Histidine hydrochlorate can be use its crystalline hydrate (histidine hydrochloride 1 hydrate) (C ₆h ₉n ₃o ₂hClH ₂o), glucose comprises its hydrate, glucose 1 hydrate, the crystalline hydrate of sorbitol or xylitol or mannitol, if use its anhydride, its content or inventory can be converted accordingly according to molecular weight; This does not hinder other component use or do not use, and when deployed, can carry out according to chemistry or pharmacy or biomedical rule.

In pharmaceutical composition of the present invention, the amount of each component or the pharmaceutically acceptable form of difference (comprising its salt or hydrate) of each component can rationally change or adjust, to form different combinations in the certain limit that the present invention specifies.

The supplementary material that the present invention mentions or former, that adjuvant refers to different pharmaceutical properties component, divide from treatment or pharmacological function, with 18 kinds of different aminoacids, sorbitol or xylitol or mannitol or xylose or glucose, fructose for raw material or principal agent or principal agent component; Antioxidant or stabilizing agent, pH adjusting agent, water for injection and active carbon etc. are adjuvant.

The pharmaceutical composition of Amino Acid Compound Injection 18AA of the present invention, can contain pharmaceutically acceptable antioxidant or stabilizing agent in the solution of this pharmaceutical composition, antioxidant or stabilizing agent are selected from: tartaric acid or L-TARTARIC ACID or its salt pharmaceutically accepted, malic acid or L MALIC ACID or its salt pharmaceutically accepted, ascorbic acid and salt D-ascorbic acid thereof and L-AA and salt thereof, D-sodium ascorbate and L-AA sodium, citric acid or citric acid monohydrate compound or its salt pharmaceutically accepted, repeatedly fragrant acid, sodium sulfite, or sodium pyrosulfite, sodium ethylene diamine tetracetate calcium or sodium ethylene diamine tetracetate calcium 4 hydrate (Ca-EDTA sodium salt), disodiumedetate, EDETATE SODIUM dihydrate, ethylenediaminetetraacetic acid, aminotriacetic acid, diethylene-triamine pentaacetic acid (DTPA), glutathion, Cys, L-cysteine hydrochloride or L-cysteine hydrochloride 1 hydrate, Cys, L-threonine, L-arginine, L-Leu, 1B, L-Histidine, Valine, L-Trp, methionine or METHIONINE, etc. pharmaceutically acceptable racemization or optical activity, or DL, D or L-aminoacid or its salt pharmaceutically accepted, or one or more in its salt pharmaceutically accepted or its crystalline hydrate, containing antioxidant or stabilizing agent 0 ~ 8.0g in every 1000ml injection, more preferably form is, containing antioxidant or stabilizing agent 0.01g ~ 3.0g in every 1000ml injection.

The pH value of the solution of the pharmaceutical composition of Amino Acid Compound Injection 18AA of the present invention is 5.00-7.00.

In the preparation process of the solution of the pharmaceutical composition of Amino Acid Compound Injection 18AA of the present invention, its pH adjusting agent is selected from acetic acid, phosphoric acid, citric acid, citric acid monohydrate compound, tartaric acid, lactic acid or its salt pharmaceutically accepted, sodium hydroxide, sodium carbonate, sodium bicarbonate, meglumine, sodium bisulfate, sodium dihydrogen phosphate, sodium hydrogen phosphate or sodium hydrogen phosphate 7 hydrate or tertiary sodium phosphate, sodium acetate, sodium lactate, sodium bitartrate, sodium tartrate, one or more in the acid that trisodium citrate or trisodium citrate 2 hydrate etc. pharmaceutically accept or alkali or its crystalline hydrate, the acid pharmaceutically accepted or alkali are the lewis acid of broad sense or the lewis base of broad sense.Its pH adjusting agent pharmaceutically accepted can containing 0-20.00 gram or more at every 1000ml injection of the present invention, the pH adjusting agent used with its effective ingredient or molecular formula to calculate its weight or to calculate corresponding volume according to the data such as concentration or density.The pH adjusting agent used joins in the solution of compositions in form of an aqueous solutions in the process preparing preparation.When adopting alkaline solution to carry out adjust ph, (prepared by alkaline solution available bases, as sodium hydroxide, also can with one or more of trisodium citrate, sodium bisulfate etc.), once add excessive etc., available acid solution readjustment, to control a suitable pH value (pH is about about 5.00-7.00), vice versa.

The pharmaceutical composition of new Amino Acid Compound Injection 18AA of the present invention, its preparation method comprises:

Method one, in dispensing canister, adding appropriate water for injection, (water for injection is generally total amount 55-80%, can add time not enough), adopt evacuation and inflated with nitrogen replacement Treatment in process of production, reduce the content of oxygen in dispensing canister, under whole process fills nitrogen, to be about between 95 DEG C-50 DEG C successively or segmentation drops into supplementary material in water temperature: sorbitol or xylitol or mannitol or xylose or glucose or fructose, tyrosine, leucine, isoleucine, valine, methionine, phenylalanine, glutamic acid, Aspartic Acid, lysine or lysine acetate, threonine, glycine, arginine, alanine, proline, serine, cystine, histidine and tryptophan, be stirred to entirely molten, regulate pH to be about about 5.00-7.00 with appropriate one or more solution pharmaceutically accepting pH adjusting agent, inject and use water standardize solution to ormal weight, add 0.05-3% (w/v, w/v: grams per milliliter) medicinal carbon, uniform stirring, and keep 5-40 minute, de-charcoal circulation, again by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element, under nitrogen current protection, fine straining liquid is filled in non-PVC multi-layer co-extruded transfusion bag or infusion bottle (comprising glass infusion bottle or plastic infusion bottle), every bag or every bottle of 50ml or 100ml or 250ml or 500ml or 750ml or 1000ml or other arbitrary volume specification (200ml, 400ml, 600ml etc.), jump a queue in non-PVC multi-layer co-extruded transfusion bag sealing or infusion bottle, gland, roll aluminum lid, in 105-121 DEG C of sterilizing 8-40 minute, lamp inspection, can oxygen-inhibiting agent be put into again and put outer bag after non-PVC multi-layer co-extruded transfusion bag sealing, namely the pharmaceutical composition containing 18 seed amino acids of the present invention is obtained after sealing.If there is the loss of the components such as aminoacid in preparation process, corresponding aminoacid or sorbitol or xylitol or mannitol or xylose or glucose, fructose etc. can be added during the course by loss amount, meet prescription with the content of each component in the every 1000ml solution maintaining pharmaceutical composition of the present invention to specify or States Pharmacopoeia specifications or make its content in 90-110% or 85-115% of labelled amount or the scope of 80-110%, this is understandable in pharmaceutical field.

Method two, the preparation method of the pharmaceutical composition of Amino Acid Compound Injection 18AA of the present invention, also can comprise the following steps or method: (one): in dense preparing tank, adding appropriate water for injection, (water for injection is generally total amount 0.5-8%, can add time not enough), be filled with nitrogen and heat temperature raising, under nitrogen filled protection, add sorbitol or xylitol or mannitol or xylose or glucose, fructose, be stirred to dissolve, (2): in dense preparing tank, add appropriate water for injection, be filled with nitrogen and heat temperature raising, under nitrogen filled protection, add tyrosine, isoleucine, valine, leucine, methionine, stir and boil to whole dissolving, (3): under nitrogen protection, the lysate of (two) is lowered the temperature, add phenylalanine, glutamic acid, lysine or its salt, threonine, Aspartic Acid, glycine wherein, stirring and dissolving, (4): under nitrogen protection, the lysate of (three) is lowered the temperature, drop into proline, serine, alanine, arginine or its salt, histidine or its salt, tryptophan, cystine and antioxidant or stabilizing agent, stirring and dissolving, after stirring and dissolving, then add the solution of (one), measure pH, if pH is not between for 5.00-7.00, regulate pH to be about between 5.00-7.00 with appropriate one or more solution pharmaceutically accepting pH adjusting agent, and in this lysate, add appropriate pin charcoal carry out insulation absorption, circulate and take off charcoal, under nitrogen protection, solution is filtered to dilute preparing tank through titanium rod, is settled to full dose, add pin charcoal in the solution, be filtered to lysate clarification step by step through micropore filter after stirring, obtain the pharmaceutical composition medicinal liquid containing 18 seed amino acids, medicinal liquid is sub-packed in plastic infusion bottle or glass infusion bottle infusion bottle jumps a queue, gland, rolls in aluminium lid or non-PVC multi-layer co-extruded transfusion bag, nitrogen filled protection lower seal, in 121 DEG C of sterilizings 15 minutes or 115-117 DEG C of sterilizing 30 minutes, lamp inspection, packaging, obtain the drug combination injection product of 18 seed amino acids.Originally be prepared in layoutprocedure and whole process can rush nitrogen protection.

The preparation method of the pharmaceutical composition of method three, Amino Acid Compound Injection 18AA of the present invention, also can comprise the following steps or method: 1), in a mixer, add load weighted sorbitol or xylitol or mannitol or xylose or glucose, fructose, (water for injection is generally total amount 0.5-8% in right amount to add water for injection, can add time not enough), add 0.1-1% active carbon, agitating heating boils 15 minutes, is chilled to 65-80 DEG C, logical nitrogen 15-30 minute, stand-by; 2), dense join in cylinder to add be equivalent to the water for injection that total amount is about 50-70%, limit heating edge fills nitrogen 10-30 minute, add antioxidant or stabilizing agent during 100-90 DEG C, stir and make it dissolve, then add tyrosine, leucine, isoleucine, valine, methionine stirring and dissolving; 3), under nitrogen protection condition, to step 2) gained solution is cooled to 65-75 DEG C, add phenylalanine, glutamic acid, Aspartic Acid, lysine or its salt, threonine, glycine, arginine or its salt, alanine, proline, serine, stirring and dissolving; 4), under nitrogen protection condition, to step 3) gained solution is cooled to 45-65 DEG C, adds cystine, histidine or its salt, tryptophan, stirring and dissolving; 5), under nitrogen protection condition, to step 4) squeeze into step 1 in gained solution) solution, this solution filters de-carbon by titanium rod and squeezes into, and solution temperature is down to 36-48 DEG C, and then adds between acid or alkali adjust ph to 5.00-7.00; 6), under nitrogen protection condition, to step 5) inject in gained solution and use water standardize solution, add 0.01-1% (w/v) medicinal charcoal again to adsorb, uniform stirring, and keep 10-30 minute, de-charcoal circulation, then by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element; Conform with the regulations to visible foreign matters; after survey semi-finished product are qualified; under nitrogen current protection, fine straining liquid is filled in infusion bottle; every bottle of 50ml or 100ml or 250ml or 500ml or 750ml or 1000ml; jump a queue, gland, roll aluminium lid; 105-121 DEG C of sterilizing 8-40 minute, lamp inspection, packaging, obtain Amino Acid Compound Injection product of the present invention.

The preparation method of the pharmaceutical composition of method four, Amino Acid Compound Injection 18AA of the present invention, yet can comprise or according to following steps or method or describe according to following steps or method: (1) takes the various components meeting quality standard by every 1000ml prescription; (2) under the protection of nitrogen, with the dissolving of appropriate water for injection, (water for injection is generally about total amount 60-80%, can add time not enough), then the acceptable acid of pharmacy is used or/and alkali adjust ph to 5.0 ~ 7.0, and inject and make solution to full dose 1000ml with water, add active carbon after stirring; (3) after above-mentioned solution takes off charcoal, through filtrations such as 0.45um and 0.22um microfilter after elder generation, logical nitrogen is lower to be beaten and is circulated to visible foreign matters and conforms with the regulations, after survey semi-finished product are qualified, twice inflated with nitrogen fill is in infusion bottle, rear subpackage, jumps a queue in infusion bottle, gland, rolls in aluminium lid or non-PVC multi-layer co-extruded transfusion bag, nitrogen filled protection lower seal; (4) sterilizing 8 ~ 40 minutes at 105 ~ 121 DEG C.

The preparation method of the pharmaceutical composition of Amino Acid Compound Injection 18AA of the present invention, cystine can be appropriate diluted alkaline dissolve, be added in rare amino acid whose NaOH solution tank NaOH of joining again, or other aminoacid and sorbitol or xylitol or mannitol or xylose or glucose, fructose mixed solution in, then carry out charcoal treatment in the lump with other Freamine Ⅲ etc., this term or process are understandable in the preparation process of transfusion or amino acid transfusion.

In preparation pharmaceutical composition process of the present invention, the course of dissolution of sorbitol or xylitol or mannitol or xylose or glucose, fructose can dissolve by independent water for injection, first use separately the medicinal carbon of 0.05-3% (w/v) and keep 5-40 minute, for subsequent use after de-charcoal, and mix with Freamine Ⅲ in any one link, carry out associative operation in the lump again, whole process can rush nitrogen.In preparation process, the dissolved oxygen general control of water for injection is within 1mg/L, more excellent within 0.5mg/L.The inspection (meeting Chinese Pharmacopoeia 2005 editions or 2010 editions regulations) of visible foreign matters in preparation process, half-finished detection, can be normalization operation, can run through in each method.

In the preparation process of pharmaceutical composition of the present invention, reduce phlegm and internal heat source and degerming mode can be that the active carbon adding dosing amount 0.05-3.0% reduces phlegm and internal heat source or endotoxin, and the degerming and pressure sterilizing of microporous filter membrane, also can adopt heat sterilization, source of reducing phlegm and internal heat.The filtrations such as microporous filter membrane is degerming, general 0.45um and 0.22um microfilter.In hyperfiltration process, ultrafilter can select flat, rolling, tubular type, hollow fiber form and circle boxlike etc., preferred rolling and hollow fiber form ultrafilter, adopt retain relative molecular mass be 5 ten thousand to 30 ten thousand filter membrane remove most of heat generation material and antibacterial after, adopt the ultrafilter membrane removing residue thermal source retaining relative molecular mass 3000-60000 again, the ultrafilter membrane of preferred relative molecular mass 4000-30000.

In the preparation process of pharmaceutical composition of the present invention, the EDTA-2Na solution circulation of 0.05-0.5% (g/ml) can be used in advance to rinse rustless steel and to produce pipeline and production container 3-15 minute; Rinsing rustless steel with water for injection again and produce pipeline and production container, is 5.5-6.5 to flushing water pH value, to reduce the impact etc. that metal ion etc. is prepared medicinal composition solution of the present invention.

In the preparation method of the pharmaceutical composition of Amino Acid Compound Injection 18AA of the present invention, the step in diverse ways also can be intersected staggered or mutual or has been used alone the present invention, and this is not restriction the present invention.

The infusion bottle that the present invention uses or bag can be the infusion bottle or bag that leave enough spaces, so as to rush nitrogen displaced air protection medicinal liquid or Clinical practice process add other medicinal liquid as many as 20,50,100,200ml, 400ml, 500ml or more.To the sample of the multiple embodiments in the present invention, the investigation experiment that room temperature keeps sample 3 months is carried out according to the regulation of pharmacopeia, every preparation all meets the Chinese Pharmacopoeia regulation of 18AA Amino Acid Compound Injection, show that preparation method of the present invention is feasible, detection method is with reference to the regulation of the Amino Acid Compound Injection 18AA in 2010 editions Chinese Pharmacopoeia enlarged editions.

For the rule rounded up in the data of the amount of each component, pharmaceutically in intelligible scope or when science counts, the present invention illustrates further to this.The amount of each component in pharmaceutical composition of the present invention, for example, in a compositions, in 1000ml solution, the content of arginine or L-arginine can be 4.135 grams, also it can be 4.14 grams or 4.13 grams, or in another compositions, in 1000ml solution, the content of arginine or L-arginine can be 9.923098 grams, also can be 9.92 grams, also can be 9.93 grams, this can determine, all within range of error according to the regulation rounded up of specifying under different situations or work out or formulate or rule; In 1000ml solution, the content of the content of lysine acetate or L-lysine acetate can be the content of 4.855g can be 4.86g can be 4.85g, determine according to the regulation rounded up of specifying under different situations or work out or formulate or rule too, content in 1000ml solution can be L-Histidine or histidine 1.8504 grams or 1.85 grams, also all within range of error.Also the rest may be inferred for the amount of other all each component (such as histidine monohydrochloride, cystine, lysine etc.); Also more can analogize further according to the rule rounded up, according to the quantitative relation between the molecular weight of component itself or quality, extend on scale or in the figure place being accurate to different arithmetic point, for example, in these cases, when being accurate to six figure place after arithmetic point, in the present invention's compositions, in 1000ml solution, the content of lysine acetate or L-lysine acetate can be 11.6528705g or 11.652871g or 11.652870g.This is understandable on medicine.

The present invention not only provides sorbitol as the energy substance of human body, and provide D-glucitol or L-sorbitol, xylitol, mannitol, xylose, glucose, fructose or its crystalline hydrate as the energy substance of human body, more selection is provided, the effect maintaining heat can be played in different situations, after inputting with aminoacid simultaneously, can obviously improve amino acid whose metabolism, for the synthesis of protein provides the energy, suppress the different glycogenic waste of aminoacid, aminoacid can be utilized by body fully.Amino acid transfusion, when Power supply abundance, can enter histiocyte, participates in the anabolism of protein, obtains positive nitrogen balance, and generates enzyme, hormone, antibody, structural protein, promotes organization healing, recovers normal physiological function.

The usage and dosage of pharmaceutical composition of the present invention: be generally intravenous drip, a general 250 ~ 500ml, drip velocity generally 20 ~ 80 per minute, generally, one day can one to six times or look concrete condition increase and decrease, child's decrement.

Original new drug compositions of the present invention has numerous significant advantage or unexpected point, and this is out in the cold or do not perceiveed or more show the defect of prior art in the past.With existing Amino Acid Compound Injection 18AA product by contrast, pharmaceutical composition of the present invention more has advantage as follows:

1, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) of the new ratio containing new component lysine acetate, arginine, histidine is provided, the probability that during minimizing clinical administration, hyperchloremia occurs;

2, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) containing new component lysine acetate, arginic new ratio is provided, the probability that during minimizing clinical administration, hyperchloremia occurs;

3, the pharmaceutical composition of the new ratio containing new component lysine acetate is provided, the probability that during minimizing clinical administration, hyperchloremia occurs;

4, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) of the new ratio containing new component arginine, histidine is provided, the probability that during minimizing clinical administration, hyperchloremia occurs;

5, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) of the new ratio containing new component lysine acetate, histidine is provided, the probability that during minimizing clinical administration, hyperchloremia occurs;

6, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) containing the arginic new ratio of new component is provided, the probability that during minimizing clinical administration, hyperchloremia occurs;

Although the effect of the DL thing of methionine or DL-methionine and METHIONINE is close, can also often use with, but the DL thing of industrial alanine or DL-Alanine and ALANINE have significant difference, the DL thing of phenylalanine or DL-phenylalanine is same with L-Phe significant difference, there is half effectively can not utilize for body, be equivalent to the effective ingredient only having half in preparation; And the present invention also provides the amino acid whose pharmaceutical composition of L-type that all can absorb for human body, compare the d-isomer that generally can not effectively utilize, the selection of new selection provided by the invention or more more contributes to treatment or the rehabilitation of disease.

7, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) of the new ratio containing new component L-lysine acetate, L-arginine, L-Histidine is provided, the new nutrition supply contributing to absorbing combination is provided, more contribute to treatment or the rehabilitation of disease, the probability that when also contributing to reducing clinical administration, hyperchloremia occurs simultaneously;

8, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) of the new ratio containing new component L-lysine acetate, L-arginine is provided, the new nutrition supply absorbed combination is provided, more contribute to treatment or the rehabilitation of disease, the probability that when also contributing to reducing clinical administration, hyperchloremia occurs simultaneously;

9, the pharmaceutical composition of the new ratio containing new component L-lysine acetate is provided, the new nutrition supply absorbed combination is provided, more contributes to treatment or the rehabilitation of disease, also contribute to the probability reducing hyperchloremia generation simultaneously;

10, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) of the new ratio containing new component L-arginine, L-Histidine is provided, the new nutrition supply absorbed combination is provided, more contribute to treatment or the rehabilitation of disease, the probability that when also contributing to reducing clinical administration, hyperchloremia occurs simultaneously;

11, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) of the new ratio containing new component L-lysine acetate, L-Histidine is provided, the new nutrition supply absorbed combination is provided, more contribute to treatment or the rehabilitation of disease, the probability that when also contributing to reducing clinical administration, hyperchloremia occurs simultaneously;

12, the pharmaceutical composition of the Amino Acid Compound Injection (18AA) of the new ratio containing new component L-arginine is provided, the drug regimen of the new nutrition supply absorbed is provided, more contribute to treatment or the rehabilitation of disease, also contribute to the probability reducing hyperchloremia generation simultaneously;

13, the present invention not only provides the pharmaceutical composition containing sorbitol, and provides the pharmaceutical composition of the Amino Acid Compound Injection (18AA) containing xylitol or mannitol or glucose or fructose; The amino acid injection that the amino acid injection of the xylitol providing diabetics to use, ND use, the medicine composition injection needing the Amino Acid Compound Injection (18AA) of inducing diuresis to remove edema with cerebral edema, greatly widen the scope of application of original Amino Acid Compound Injection (18AA), this is also by being ignored in the past;

14, for there is not acidosic patient but body occur may cause potential impact and be difficult to or subtle when, there is provided a kind of preparation of pharmaceutical composition of safer Amino Acid Compound Injection (18AA), so that the balance of clinician uses;

15, when hyperpietic or dissimilar hyperpietic need Amino Acid Compound Injection (18AA), one or more are provided to use the pharmaceutical composition of Amino Acid Compound Injection (18AA) to hyperpietic or severe hypertension patient or salt form hyperpietic, this is more excellent than the past, this in the past or present clinical or clinical pharmacy ignore or get the brush-off;

16, for some patient or in some cases, appropriate or a small amount of chloride ion prevention of disease or treatment are also useful, the pharmaceutical composition of the 18AA Amino Acid Compound Injection of that the invention provides a kind of not chloride ion-containing or few in right amount chloride ion, there is provided a kind of pharmaceutical composition of more personalized or abundanter Amino Acid Compound Injection (18AA), the treatment made an allowance for different circumstances;

17, when clinical transfusion runs into more difficult judgement, give the pharmaceutical composition of new Amino Acid Compound Injection (18AA) of the present invention, better safety is obtained by making the treatment of patient, particularly necessary in some cases, be conducive to clinician and process the follow-up state of an illness further with normal saline or normal saline medicine at any time;

18, to the treatment of part Therapy of Intensive Craniocerebral Trauma, cerebral hemorrhage, trauma patient, hepatitis or liver cirrhosis or hepatic ascites patient etc., for reducing case fatality rate, its prognosis is improved, for clinical treatment provides a safer and more effective selection;

19, to suffer from infantile autism but need the patient of supplementary Amino Acid Compound Injection (18AA), provide the selection that is safer and more effective or more, perhaps this more current pharmacy or clinical ignore or have no promotion;

20, provide containing new antioxidant or stabilizing agent or do not contain or less containing the pharmaceutical composition of sodium sulfite, be conducive to reducing following potential adverse reaction rate;

21, based on relevant pharmacy or pharmacology or clinical, pharmaceutical composition of the present invention also has other advantage in various degree.

Detailed description of the invention

During except there being instruction in an embodiment and separately, in description and claims, all numerical value used should be understood to be in all examples and modify with term " about ", therefore, unless the contrary indication, numerical parameter given in this description and appending claims is approximation, it can change according to by character required for sought by present disclosure, at least, and not the application being intended to limit doctrine of equivalents right, each numerical parameter should consider that the number of significant digits and the routine method of rounding up are explained.

Although numerical range and the parameter of the wide region of setting disclosure are approximations.But numerical value given in a particular embodiment is as far as possible accurately reported, any number comprises some error certainly led to by the standard deviation found in their respective tests in essence.

Unless it is pointed out that in literary composition and illustrated in addition clearly, the singulative " " used in this specification and the appended claims, " one " and " being somebody's turn to do " comprise the plural form referring to thing, so, such as.If comprise the mixture of two or more compounds when mentioning the compositions containing " a kind of compound ", unless it should be noted that in addition and illustrate in addition clearly herein, term "or" generally includes "and/or".

As used herein, term " obtains " referring to that valuable content or purity level are separated the compound obtained, and described content or purity level include but not limited to be greater than 90%, the content of 95%, 96%, 97%, 98% and 99% or purity level.Described content or purity level can be measured by methods such as high performance liquid chromatography.

" solvate " that the present invention mentions refers to the crystal formation of molecule, atom and/or the ion also comprising the solvent molecule penetrated in crystal structure herein, the solvent molecule of solvate can be in regularly arranged and/or lack of alignment, the present invention mentions the hydrate that aminoacid or amino acid salts comprise aminoacid or amino acid salts, glucose comprises its hydrate, pharmaceutically acceptable pH adjusting agent comprises the crystalline hydrate of these pH adjusting agents, and antioxidant also comprises its crystalline hydrate or optical isomer or raceme.

Pharmaceutical composition: " pharmaceutical composition " used herein refers to the compositions of medicine, described pharmaceutical composition can contain the pharmaceutically acceptable carrier of at least one.

" pharmaceutically acceptable excipient " used herein refers to the pharmaceutical carrier or solvent that are applicable to the compound administration occasionally provided herein, and it comprises any examples of such carriers that well known to a person skilled in the art and be applicable to specific administration mode.

As non-limiting example, the pharmaceutical composition of Amino Acid Compound Injection 18AA can optionally mix by adjuvant pharmaceutically acceptable with one or more, and can with following form with sterile solution agent form parenteral.In the preparation transfusion of each embodiment or injection process, the system all will prepared infusion solutions and pipeline clean in advance, this be also necessity in Producing Process of Transfusion or normality, describe no longer one by one in embodiments.

Volume unit is milliliter (ml) or rises (L) etc., and unit of weight is gram (g) or kilogram (kg); Concentration unit is molar concentration (M or mol/L) or equivalent concentration (N) or percent concentration etc.

In order to understand the present invention further, below in conjunction with embodiment, the preferred embodiment of the invention is described, but should be appreciated that these describe just for further illustrating feature of the present invention or effect or advantage, instead of limiting to the claimed invention.

The preparation of embodiment 1, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 10.00 grams; Serine 10.00 grams; ALANINE 20.00 grams; ILE 35.2 grams; L-Leu 49.0 grams; L-ASPARTIC ACID 25.0 grams; TYR 2.50 grams; Pidolidone 7.5 grams; L-Phe 53.30 grams; L-arginine 41.35 grams; L-lysine acetate 48.55 grams; Valine 36.0 grams; L-threonine 25.0 grams; L-Histidine 18.5 grams; L-Trp 9.0 grams; METHIONINE 22.5 grams; CYSTINE 1.0 grams; Glycine 76.0 grams; Sorbitol 500.0 grams; Sodium sulfite 5.0 grams;

Preparation technology:

Each former, adjuvant is taken by prescription, in dispensing canister, add 8L water for injection, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in Agitation Tank, then under whole process fills nitrogen, between water temperature 96 DEG C-85 DEG C, drop into supplementary material successively: sorbitol, antioxidant (sodium sulfite), TYR, L-Leu, ILE, Valine, METHIONINE, is stirred to entirely molten, treats that temperature of liquid drops between 85C °-65 DEG C and drop into L-Phe successively in above-mentioned Agitation Tank, Pidolidone, L-ASPARTIC ACID, L-lysine acetate, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, is stirred to entirely molten, treats that solution temperature drops to 45-65 DEG C, add CYSTINE, L-Histidine and L-Trp, be stirred to entirely molten, pH is regulated to be about about 5.83 with the acetic acid of 0.2M and the sodium hydroxide solution of 0.2M, inject and use water standardize solution to ormal weight, add 4 grams of medicinal carbons, uniform stirring, and keep 15 minutes, de-charcoal circulation, then by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element, conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid is filled in infusion bottle, every bottle of 100ml or 250ml or 500ml, jump a queue, gland, roll aluminium lid, in 115 DEG C of sterilizing 30min, after the assay was approved, the medicine composition injection containing 18 seed amino acids of the present invention is obtained.

Each amino acid content in the pharmaceutical composition of the present invention adopting amino-acid analyzer mensuration room temperature to keep sample 3 months, find all in the scope of prescription labelled amount 80-120%, in addition, the content etc. of the character of solution, visible foreign matters, light transmittance, pH value, endotoxin, sorbitol all meets the regulation of 2010 editions Chinese Pharmacopoeia enlarged edition Amino Acid Compound Injection 18AA.

The preparation of embodiment 2, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 10.00 grams;

Serine 10.00 grams;

ALANINE 20.00 grams;

ILE 35.2 grams;

L-Leu 49.0 grams;

L-ASPARTIC ACID 25.0 grams;

TYR 2.5 grams;

Pidolidone 7.5 grams;

L-Phe 53.3 grams;

L-arginine 41.35 grams;

L-lysine acetate 48.55 grams;

Valine 36.0 grams;

L-threonine 25.0 grams;

L-Histidine 18.5 grams;

L-Trp 9.0 grams;

METHIONINE 22.5 grams;

CYSTINE 1.0 grams;

Glycine 76.0 grams;

Sorbitol 500.0 grams;

Calcium disodium edetate 0.5 gram (antioxidant);

2.0 grams, tartaric acid (antioxidant)

Preparation technology:

Each former, adjuvant is taken by prescription, in dispensing canister, add 7.5L water for injection, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in dispensing canister, then under whole process fills nitrogen, between water temperature 95 DEG C-85 DEG C, drop into the supplementary material of recipe quantity successively: sorbitol, antioxidant (calcium disodium edetate, tartaric acid), TYR, L-Leu, ILE, Valine, METHIONINE, is stirred to entirely molten, treats that temperature of liquid drops between 85C °-65 DEG C and drop into L-Phe successively in above-mentioned Agitation Tank, Pidolidone, L-ASPARTIC ACID, L-lysine acetate, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, is stirred to entirely molten, treats that solution temperature drops to 45-65 DEG C, add CYSTINE, L-Histidine and L-Trp, be stirred to entirely molten, regulate pH5.87 by the acetic acid of 0.16N and the NaOH solution of 0.16N, add 5 grams of medicinal carbons and keep 15 minutes, de-charcoal circulation, inject with water standardize solution to ormal weight, uniform stirring, and keep 15 minutes, de-charcoal circulation, again by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element, conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid is filled in infusion bottle, every bottle of 100ml or 250ml or 500ml, jump a queue, gland, roll aluminium lid, in 115 DEG C of sterilizing 30min, after the assay was approved, the medicine composition injection containing 18 seed amino acids of the present invention is obtained.

Each amino acid whose content in the pharmaceutical composition of the present invention adopting amino-acid analyzer mensuration room temperature to keep sample 3 months, find all in the scope of prescription labelled amount 80-120%, in addition, after testing, find that the content etc. of the character of solution, visible foreign matters, light transmittance, pH value, endotoxin, sorbitol all meets the relevant regulations of the Amino Acid Compound Injection 18AA in 2010 editions Chinese Pharmacopoeia enlarged editions.

The preparation of embodiment 3, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 11.00 grams; Serine 10.00 grams; ALANINE 20.00 grams; ILE 35.2 grams; L-Leu 49.0 grams; L-ASPARTIC ACID 25.0 grams; TYR 2.50 grams; Pidolidone 7.5 grams; L-Phe 53.30 grams; L-arginine 48.35 grams; L-lysine acetate 48.55 grams; Valine 36.0 grams; L-threonine 25.0 grams; L-Histidine 18.5 grams; L-Trp 9.0 grams; Methionine 25.2 grams; CYSTINE 1.0 grams; Glycine 76.0 grams; Xylitol 500.00 grams; Calcium disodium edetate 0.5 gram, citric acid 5 grams;

Preparation technology:

Each former, adjuvant is taken by prescription; 1), in a mixer, add the xylitol of recipe quantity, add fresh water for injection 1L, be stirred to dissolve, add 0.3 gram of active carbon, agitating heating boils 20 minutes, is chilled to 65-80 DEG C, logical nitrogen 20 minutes, stand-by; 2), join in cylinder dense the water for injection adding 7L, limit heating edge fills nitrogen, antioxidant (calcium disodium edetate, citric acid) is added during 95-90 DEG C, stirring makes it dissolve, then adds TYR, L-Leu, ILE, Valine, the methionine stirring and dissolving of recipe quantity; 3), under nitrogen protection condition, to step 2) gained solution is cooled to 65-75 DEG C, add the L-Phe of recipe quantity, Pidolidone, L-ASPARTIC ACID, L-lysine acetate, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, stirring and dissolving; 4), under nitrogen protection condition, to step 3) gained solution is cooled to 45-65 DEG C, adds CYSTINE, L-Histidine and L-Trp, stirring and dissolving; 5), under nitrogen protection condition, to step 4) squeeze into step 1 in gained solution) solution, this solution filters de-carbon by titanium rod and squeezes into, and solution temperature is down to 36-48 DEG C, and then the pH value of the acetic acid and NaOH solution adjustment solution that add 0.1M is to 5.82; 6), under nitrogen protection condition, to step 5) inject in gained solution and use water standardize solution, add 0.2% (w/v) medicinal charcoal and adsorb, uniform stirring, and keep 25 minutes, de-charcoal circulation, again by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element; Conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid is filled in infusion bottle; every bottle of 100ml or 250ml; jump a queue, gland, roll aluminium lid, 115 DEG C of sterilizings 30 minutes, after the assay was approved, obtain Amino Acid Compound Injection product of the present invention.

Each amino acid whose content in the pharmaceutical composition of the present invention adopting amino-acid analyzer mensuration room temperature to keep sample 3 months, find all in the scope of prescription labelled amount 80-120%, in addition, after testing, find that the character, visible foreign matters, light transmittance, pH value, endotoxin etc. of solution all meet the relevant regulations of 2010 editions Chinese Pharmacopoeia enlarged editions.

The preparation of embodiment 4, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 10.00 grams;

Serine 10.00 grams;

ALANINE 20.00 grams;

ILE 35.2 grams;

L-Leu 49.0 grams;

L-ASPARTIC ACID 25.0 grams;

TYR 2.5 grams;

Pidolidone 7.5 grams;

L-Phe 53.3 grams;

L-arginine 41.35 grams;

L-lysine acetate 48.55 grams;

Valine 36.0 grams;

L-threonine 25.0 grams;

L-Histidine hydrochlorate (C ₆h ₉n ₃o ₂hClH ₂o) 25.0 grams;

L-Trp 9.0 grams;

METHIONINE 22.5 grams;

CYSTINE 1.0 grams;

Glycine 76.0 grams;

Sorbitol 500.00 grams;

Sodium sulfite 5.0 grams;

Preparation technology:

Each former, adjuvant is taken by prescription, in dispensing canister, add 8L water for injection, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in dispensing canister, then under whole process fills nitrogen, between water temperature 95 DEG C-50 DEG C, drop into supplementary material successively: xylitol, TYR, L-Leu, ILE, Valine, sodium sulfite, METHIONINE, L-Phe, Pidolidone, L-ASPARTIC ACID, L-lysine acetate, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, CYSTINE, L-Histidine hydrochlorate and L-Trp, be stirred to entirely molten, be 5.83 by the acetic acid of 0.1M and NaOH solution adjust ph, add the medicinal carbon of 0.4% (w/v) and keep 15 minutes, de-charcoal circulation, inject with water standardize solution to ormal weight, uniform stirring, again by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element, conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid being filled to fine straining liquid is filled in infusion bottle, and every bottle of 250ml or 500ml, jumps a queue, gland, roll aluminium lid, in 121 DEG C of sterilizing 15min, after the assay was approved, obtain the pharmaceutical composition of 18 seed amino acids of the present invention.

Each amino acid whose content in the pharmaceutical composition of the present invention adopting amino-acid analyzer mensuration room temperature to keep sample 3 months, find all in the scope of prescription labelled amount 80-120%, in addition, after testing, find that the content etc. of the character of solution, visible foreign matters, light transmittance, pH value, endotoxin, sorbitol all meets the relevant regulations of the Amino Acid Compound Injection 18AA in 2010 editions Chinese Pharmacopoeia enlarged editions.

The preparation of embodiment 5, Amino Acid Compound Injection (18AA), prescription

L-PROLINE 10.00 grams;

Serine 10.00 grams;

ALANINE 20.00 grams;

ILE 35.2 grams;

L-Leu 49.0 grams;

L-ASPARTIC ACID 25.0 grams;

TYR 2.5 grams;

Pidolidone 7.5 grams;

L-Phe 53.3 grams;

L-arginine 41.35 grams;

1B 34.50 grams;

Valine 36.0 grams;

L-threonine 25.0 grams;

L-Histidine hydrochlorate (C ₆h ₉n ₃o ₂hClH ₂o) 25.0 grams

L-Trp 9.0 grams;

METHIONINE 22.5 grams;

CYSTINE 1.0 grams;

Glycine 76.0 grams;

Xylitol 500.00 grams;

Sodium sulfite 5.0 grams;

Preparation technology:

Each former, adjuvant is taken by prescription, in dispensing canister, add the water for injection of 8L, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in dispensing canister, then under whole process fills nitrogen, between water temperature 96 DEG C-50 DEG C, drop into supplementary material successively: xylitol, sodium sulfite, TYR, L-Leu, ILE, Valine, METHIONINE, L-Phe, Pidolidone, L-ASPARTIC ACID, 1B, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, CYSTINE, L-Histidine hydrochlorate and L-Trp, be stirred to entirely molten, when solution temperature about 40 DEG C, be 5.82 by the acetic acid of 0.1M and NaOH solution adjust ph, inject and use water standardize solution to ormal weight, add the medicinal carbon of 0.2% (w/v) and keep 25 minutes, uniform stirring, de-charcoal circulation, again by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element, conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid is filled in non-PVC multi-layer co-extruded transfusion bag, every bag of 250ml or 500ml, sealing, in 110-121 DEG C of sterilizing 5-40min, lamp inspection, then put into oxygen-inhibiting agent and put outer bag, sealing, after the assay was approved, the pharmaceutical composition containing 18 seed amino acids of the present invention is obtained.

The preparation of embodiment 6, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 10.00 grams; Serine 10.00 grams; ALANINE 20.00 grams; ILE 35.2 grams; L-Leu 49.0 grams; L-ASPARTIC ACID 25.0 grams; TYR 2.50 grams; Pidolidone 7.5 grams; L-Phe 53.30 grams; L-arginine 41.35 grams; LYS 43.00g gram; Valine 36.0 grams; L-threonine 25.0 grams; L-Histidine 18.5 grams; L-Trp 9.0 grams; Methionine 22.5 grams; CYSTINE 1.0 grams; Glycine 76.0 grams; Sorbitol 500.00 grams; Sodium sulfite 4.0g, calcium disodium edetate 0.5 gram,

Preparation technology:

Each former, adjuvant is taken by prescription, in dispensing canister, add 8L water for injection, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in Agitation Tank, then under whole process fills nitrogen, between water temperature 96 DEG C-85 DEG C, drop into supplementary material successively: sorbitol, calcium disodium edetate, sodium sulfite, TYR, L-Leu, ILE, Valine, is stirred to entirely molten, treats that temperature of liquid drops between 85C °-65 DEG C and drop into L-Phe successively in above-mentioned Agitation Tank, methionine, Pidolidone, L-ASPARTIC ACID, LYS, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, is stirred to entirely molten, treats that solution temperature drops to 45-65 DEG C, add CYSTINE, L-Histidine and L-Trp, be stirred to entirely molten, pH is regulated to be about about 5.85 with the acetic acid of 0.1M and the sodium hydroxide solution of 0.1M, inject and use water standardize solution to ormal weight, add the medicinal carbon of 0.09% (w/v), uniform stirring, and keep 15 minutes, de-charcoal circulation, then by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element, conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid is filled in defeated non-PVC multi-layer co-extruded transfusion bag, every bag of 250ml or 500ml, sealing, in 110 DEG C-121 DEG C sterilizing 5-40min, lamp inspection, then put into oxygen-inhibiting agent and put outer bag, sealing, after the assay was approved, the pharmaceutical composition containing 18 seed amino acids of the present invention is obtained.

The preparation of embodiment 7, Amino Acid Compound Injection (18AA), prescription

L-PROLINE 10.00 grams;

Serine 10.00 grams;

ALANINE 20.00 grams;

ILE 35.2 grams;

L-Leu 49.0 grams;

L-ASPARTIC ACID 25.0 grams;

TYR 2.5 grams;

Pidolidone 7.5 grams;

L-Phe 53.3 grams;

L-arginine hydrochloride 50.00 grams,

L-lysine acetate 48.55 grams;

Valine 36.0 grams;

L-threonine 25.0 grams;

L-Histidine 18.5 grams;

L-Trp 9.0 grams;

METHIONINE 22.5 grams;

CYSTINE 1.0 grams;

Glycine 76.0 grams;

500.0 grams, mannitol;

Sodium sulfite 5.0 grams

Preparation technology:

Each former, adjuvant is taken by prescription, 8L water for injection is added in dispensing canister, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in dispensing canister, then under whole process fills nitrogen, supplementary material is dropped into successively: mannitol between water temperature 100 DEG C-50 DEG C, TYR, L-Leu, ILE, Valine, METHIONINE, L-Phe, Pidolidone, L-ASPARTIC ACID, L-lysine acetate, L-threonine, glycine, L-arginine hydrochloride, ALANINE, L-PROLINE, Serine, CYSTINE, L-Histidine and L-Trp, be stirred to entirely molten, with acetic acid or the NaOH solution adjustment pH to 6.35 of 0.1M, add the medicinal carbon of 0.1% (w/v) and keep 15 minutes, de-charcoal circulation, inject with water standardize solution to ormal weight, uniform stirring, again by coarse filtration liquid through 0.45um, the continuous fine straining of 0.22um micropore filter element, under nitrogen current protection, fine straining liquid is filled in non-PVC multi-layer co-extruded transfusion bag, every bag of 100ml or 250ml or 500ml, sealing, in 110 DEG C-121 DEG C sterilizing 5-40min, lamp inspection, put into oxygen-inhibiting agent again and put outer bag, after sealing, namely obtaining a kind of pharmaceutical composition containing 18 seed amino acids of the present invention.

The preparation of embodiment 8, Amino Acid Compound Injection (18AA), prescription:

Proline 10.00 grams; Serine 10.00 grams; Alanine 20.00 grams; Isoleucine 35.2 grams; Leucine 49.0 grams; Aspartic Acid 25.0 grams; 2.5 grams, tyrosine; 7.5 grams, glutamic acid; Phenylalanine 53.3 grams; Arginine 41.35 grams; Lysine acetate 48.55 grams; Valine 36.0 grams; Threonine 25.0 grams; Histidine 18.5 grams; Tryptophan 9.0 grams; Methionine 22.5 grams; Cystine 1.0 grams; Glycine 76.0 grams; Sorbitol 500.00 grams; Sodium sulfite 5.0 grams;

Preparation technology: prepared by the preparation method with reference to embodiment 1, obtain the transfusion of Amino Acid Compound Injection of the present invention (18AA) pharmaceutical composition.

The preparation of embodiment 9, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 12.0 grams; Serine 12.0 grams; ALANINE 24.0 grams; ILE 40.2 grams; L-Leu 42.0 grams; L-ASPARTIC ACID 20.0 grams; TYR 2.8 grams; Pidolidone 6.2 grams; L-Phe 59.3 grams; L-arginine 41.35 grams; L-lysine acetate 48.55 grams; Valine 39.0 grams; L-threonine 27.0 grams; L-Histidine 15.5 grams; L-Trp 9.5 grams; METHIONINE 25.5 grams; CYSTINE 1.2 grams; Glycine 86.0 grams; Sorbitol 452.00 grams; Disodiumedetate 0.1g; Tartaric acid monohydrate 8.0 grams; Sodium tartrate 21.5 grams;

Preparation technology: take each former, adjuvant by prescription, appropriate water for injection is added in dispensing canister, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in dispensing canister, then under whole process fills nitrogen, supplementary material is dropped into successively: calcium disodium edetate between water temperature 100 DEG C-50 DEG C, tartaric acid monohydrate, sodium tartrate, sorbitol, TYR, L-Leu, ILE, Valine, METHIONINE, L-Phe, Pidolidone, L-ASPARTIC ACID, L-lysine acetate, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, CYSTINE, L-Histidine and L-Trp, be stirred to entirely molten, pH is regulated to be about about 6.20 with the lactic acid of 0.1M and the sodium citrate solution of 0.5M, add the medicinal carbon of 0.08% (w/v) and keep 25 minutes, de-charcoal circulation, inject with water standardize solution to ormal weight, uniform stirring, again by coarse filtration liquid through 0.45um, the continuous fine straining of 0.22um micropore filter element, under nitrogen current protection, fine straining liquid is filled in infusion bottle, every bottle of 100ml or 250ml or 500ml, jumps a queue, gland, roll aluminium lid, in 115 DEG C of sterilizing 30min, lamp inspection, sealing, after the assay was approved, Amino Acid Compound Injection of the present invention (18AA) pharmaceutical composition is obtained.

The preparation of embodiment 10, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 8.0 grams; Serine 8.0 grams; ALANINE 20.00 grams; ILE 35.2 grams; L-Leu 49.0 grams; L-ASPARTIC ACID 25.0 grams; TYR 2.5 grams; Pidolidone 7.5 grams; L-Phe 53.3 grams; L-arginine 49.5 grams; L-lysine acetate 66.5 grams; Valine 36.0 grams; L-threonine 25.0 grams; L-Histidine 18.5 grams; L-Trp 9.0 grams; METHIONINE 27.0 grams; CYSTINE 1.0 grams; Glycine 76.0 grams; Sorbitol 500.00 grams; Calcium disodium edetate 0.5g

Preparation technology: take each former, adjuvant by prescription, appropriate water for injection is added in dispensing canister, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in dispensing canister, then under whole process fills nitrogen, supplementary material is dropped into successively: sorbitol between water temperature 100 DEG C-50 DEG C, TYR, L-Leu, ILE, Valine, METHIONINE, L-Phe, Pidolidone, L-ASPARTIC ACID, L-lysine acetate, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, CYSTINE, L-Histidine and L-Trp, be stirred to entirely molten, with the acetic acid of 0.1M or/and the sodium hydroxide solution of 0.1M regulates pH to be about 5.40, add the medicinal carbon of 0.2% (w/v) and keep 20 minutes, de-charcoal circulation, inject with water standardize solution to ormal weight, uniform stirring, again by coarse filtration liquid through 0.45um, the continuous fine straining of 0.22um micropore filter element, under nitrogen current protection, fine straining liquid is filled in non-PVC multi-layer co-extruded transfusion bag, every bag of 250ml or 500ml, sealing, in 115 DEG C of sterilizing 30min, lamp inspection, then put into oxygen-inhibiting agent and put outer bag, namely obtain a kind of pharmaceutical composition containing 18 seed amino acids of the present invention after sealing.

The preparation of embodiment 11, Amino Acid Compound Injection (18AA), prescription:

Proline 1.00 grams; Serine 1.00 grams; ALANINE 2.00 grams; ILE 3.52 grams; L-Leu 4.90 grams; L-ASPARTIC ACID 2.50 grams; TYR 0.25 gram; Pidolidone 0.75 gram; L-Phe 5.33 grams; L-arginine 4.95 grams; L-lysine acetate 6.65 grams; Valine 3.60 grams; L-threonine 3.00 grams; L-Histidine 1.85 grams; L-Trp 0.90 gram; METHIONINE 2.70 grams; CYSTINE 0.10 gram; Glycine 7.60 grams; Xylitol 45.00 grams;

Preparation: prepared by the preparation method with reference to embodiment 2, obtain the transfusion of Amino Acid Compound Injection of the present invention (18AA) pharmaceutical composition.

The preparation of embodiment 12, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 1.00 grams; Serine 1.00 grams; ALANINE 2.00 grams; ILE 3.52 grams; L-Leu 4.90 grams; L-ASPARTIC ACID 2.50 grams; TYR 0.25 gram; Pidolidone 0.75 gram; L-Phe 5.33 grams; L-arginine 4.135 grams; L-lysine acetate 4.855 grams; Valine 3.60 grams; L-threonine 2.50 grams; L-Histidine 1.85 grams; L-Trp 0.90 gram; METHIONINE 2.25 grams; CYSTINE 0.10 gram; Glycine 7.60 grams; Sorbitol 55.00 grams; Sodium sulfite 0.40 gram;

Preparation method: prepared by the preparation method according to embodiment 1, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.

The preparation of embodiment 13, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 1.00 grams; Serine 1.00 grams; ALANINE 2.00 grams; ILE 3.52 grams; L-Leu 4.90 grams; L-ASPARTIC ACID 2.50 grams; TYR 0.25 gram; Pidolidone 0.75 gram; L-Phe 5.33 grams; L-arginine 4.14 grams; L-lysine acetate 4.86 grams; Valine 3.60 grams; L-threonine 2.50 grams; L-Histidine 1.85 grams; L-Trp 0.90 gram; Methionine 2.25 grams; CYSTINE 0.10 gram; Glycine 7.60 grams; Sorbitol 50.00 grams; Citric acid 0.40 gram, cysteine;

Prepared by the preparation method with reference to embodiment 3, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.

The preparation of embodiment 14, Amino Acid Compound Injection (18AA), prescription:

Proline 12.0 grams; Serine 12.0 grams; Alanine 24.0 grams; Isoleucine 40.2 grams; Leucine 42.0 grams; Aspartic Acid 20.0 grams; 2.8 grams, tyrosine; 6.2 grams, glutamic acid; Phenylalanine 59.3 grams; Arginine 41.35 grams; Lysine acetate 48.55 grams; Valine 39.0 grams; Threonine 27.0 grams; Histidine 15.5 grams; Tryptophan 9.5 grams; Methionine 25.5 grams; Cystine 1.2 grams; Glycine 86.0 grams; Sorbitol 452.00 grams; Antioxidant disodiumedetate 0.1g; L MALIC ACID 2.0 grams; 2.0 grams, L MALIC ACID sodium;

Preparation: prepared by the preparation method with reference to embodiment 1, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.

The preparation of embodiment 15, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 12.0 grams; Serine 12.0 grams; Alanine 24.0 grams; Isoleucine 40.2 grams; Leucine 42.0 grams; L-ASPARTIC ACID 20.0 grams; 2.8 grams, tyrosine; Pidolidone 6.2 grams; Phenylalanine 59.3 grams; Arginine 41.35 grams; Lysine acetate 48.55 grams; Valine 39.0 grams; Threonine 27.0 grams; L-Histidine 15.5 grams; L-Trp 9.5 grams; Methionine 25.5 grams; Cystine 1.2 grams; Glycine 86.0 grams; Sorbitol 452.00 grams; Antioxidant disodiumedetate 0.1g; Sodium ascorbate 2.0 grams, sodium pyrosulfite 2.0 grams;

Preparation: prepared by the preparation method with reference to embodiment 3, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.

The preparation of embodiment 16, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 24.0 grams;

Serine 24.0 grams;

ALANINE 48.0 grams;

ILE 84.5 grams;

L-Leu 117.6 grams;

L-ASPARTIC ACID 60.0 grams;

TYR 6.0 grams;

Pidolidone 18.0 grams;

L-Phe 128.0 grams;

L-arginine 99.23 grams;

L-lysine acetate 116.5 grams;

Valine 86.4 grams;

L-threonine 60.0 grams;

L-Histidine 44.4 grams;

L-Trp 21.6 grams;

METHIONINE 54.0 grams;

CYSTINE 2.4 grams;

Glycine 182.4 grams;

Sorbitol 500.00 grams;

Sodium sulfite 5.0 grams;

Preparation technology: take each former, adjuvant by prescription; 1), in a mixer, add the sorbitol of recipe quantity, add water for injection 1.5L, be stirred to dissolve, add 4 grams of needle-use activated carbons, agitating heating boils 20 minutes, is chilled to 65-80 DEG C, logical nitrogen 20 minutes, stand-by; 2), dense join in cylinder the water for injection adding 7L, limit heating edge fills nitrogen, adds the TYR of recipe quantity, L-Leu, ILE, Valine, L-Phe stirring and dissolving during 95-85 DEG C; 3), under nitrogen protection condition, to step 2) gained solution is cooled to 65-75 DEG C, add the Pidolidone of recipe quantity, L-ASPARTIC ACID, L-lysine acetate, L-threonine, methionine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, stirring and dissolving; 4), under nitrogen protection condition, to step 3) gained solution is cooled to 45-65 DEG C, adds CYSTINE, L-Histidine and L-Trp, stirring and dissolving; 5), under nitrogen protection condition, to step 4) squeeze into step 1 in gained solution) solution, this solution filters de-carbon by titanium rod and squeezes into, and solution temperature is down to 36-48 DEG C, and then the pH value of the acetic acid and NaOH solution adjustment solution that add 0.1M is to 5.80; 6), under nitrogen protection condition, to step 5) inject in gained solution and use water standardize solution, add 4 grams of medicinal charcoal and adsorb, uniform stirring, and keep 20 minutes, de-charcoal circulation, then by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element; Conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid is filled in infusion bottle; every bottle of 100ml or 250ml; jump a queue, gland, roll aluminium lid, at 115 DEG C of sterilizings 30 minutes, lamp inspection, after the assay was approved, obtain Amino Acid Compound Injection product of the present invention.

Each amino acid whose content in the pharmaceutical composition of the present invention adopting amino-acid analyzer mensuration room temperature to keep sample 3 months, find all in the scope of prescription labelled amount 80-120%, in addition, after testing, find that the content etc. of the character of solution, visible foreign matters, light transmittance, pH value, endotoxin, sorbitol all meets the regulation of 2010 editions Chinese Pharmacopoeia enlarged edition Amino Acid Compound Injection 18AA.

The preparation of embodiment 17, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 24.0 grams; Serine 24.0 grams; ALANINE 48.0 grams; ILE 84.5 grams; L-Leu 117.6 grams; L-ASPARTIC ACID 60.0 grams; TYR 6.0 grams; Pidolidone 18.0 grams; L-Phe 128.0 grams; L-arginine 99.23 grams; L-lysine acetate 116.5 grams; Valine 86.4 grams; L-threonine 60.0 grams; L-Histidine 44.4 grams; L-Trp 21.6 grams; Methionine 54.0 grams; CYSTINE 2.4 grams; Glycine 182.4 grams; Xylitol 500.00 grams;

Preparation: take each former, adjuvant by prescription; 1), in a mixer, add the xylitol of recipe quantity, add water for injection 900ml, be stirred to dissolve, add 3 grams of needle-use activated carbons, agitating heating boils 20 minutes, is chilled to 65-80 DEG C, logical nitrogen 20 minutes, stand-by; 2), dense join in cylinder the water for injection adding 7L, limit heating edge fills nitrogen, adds the TYR of recipe quantity, L-Leu, ILE, Valine, L-Phe stirring and dissolving during 95-85 DEG C; 3), under nitrogen protection condition, to step 2) gained solution is cooled to 65-75 DEG C, add the Pidolidone of recipe quantity, L-ASPARTIC ACID, L-lysine acetate, L-threonine, methionine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, stirring and dissolving; 4), under nitrogen protection condition, to step 3) gained solution is cooled to 45-65 DEG C, adds CYSTINE, L-Histidine and L-Trp, stirring and dissolving; 5), under nitrogen protection condition, to step 4) squeeze into step 1 in gained solution) solution, this solution filters de-carbon by titanium rod and squeezes into, and solution temperature is down to 36-48 DEG C, and then the pH value of the citric acid and NaOH solution adjustment solution that add 0.1M is to 5.86; 6), under nitrogen protection condition, to step 5) inject in gained solution and use water standardize solution, add 5 grams of medicinal charcoal and adsorb, uniform stirring, and keep 20 minutes, de-charcoal circulation, then by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element; Conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid is filled in infusion bottle; every bottle of 100ml or 250ml; jump a queue, gland, roll aluminium lid, in 115 DEG C of sterilizings 30 minutes, lamp inspection, packaging, obtain Amino Acid Compound Injection product of the present invention.

Each amino acid whose content in the pharmaceutical composition of the present invention adopting amino-acid analyzer mensuration room temperature to keep sample 3 months, find all in the scope of prescription labelled amount 80-120%, in addition, after testing, find that the character, visible foreign matters, light transmittance, pH value, endotoxin etc. of solution all meet the regulation of 2010 editions Chinese Pharmacopoeia enlarged editions.

The preparation of embodiment 18, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 28.0 grams; Serine 28.0 grams; ALANINE 48.0 grams; ILE 71.5 grams; L-Leu 137.6 grams; L-ASPARTIC ACID 70.0 grams; TYR 6.0 grams; Pidolidone 18.0 grams; L-Phe 128.0 grams; L-arginine 89.23 grams; L-lysine acetate 100.5 grams; Valine 76.4 grams; L-threonine 50.0 grams; L-Histidine 37.4 grams; L-Trp 18.6 grams; METHIONINE 64.0 grams; CYSTINE 2.0 grams; Glycine 162.4 grams; Sorbitol 450.00 grams; Sodium sulfite 5.0 grams; Calcium disodium edetate 0.5g;

Preparation: take each former, adjuvant by prescription, in dispensing canister, add 8L water for injection, heated and boiled, repeatedly adopt evacuation and inflated with nitrogen replacement Treatment, reduce the content of oxygen in dispensing canister, then under whole process fills nitrogen, between water temperature 95 DEG C-85 DEG C, drop into the supplementary material of recipe quantity successively: sorbitol, antioxidant (calcium disodium edetate, sodium sulfite), TYR, L-Leu, ILE, Valine, METHIONINE, is stirred to entirely molten, treats that temperature of liquid drops between 85C °-65 DEG C and drop into L-Phe successively in above-mentioned Agitation Tank, Pidolidone, L-ASPARTIC ACID, L-lysine acetate, L-threonine, glycine, L-arginine, ALANINE, L-PROLINE, Serine, is stirred to entirely molten, treats that solution temperature drops to 45-65 DEG C, add CYSTINE, L-Histidine and L-Trp, be stirred to entirely molten, with acetic acid and the NaOH solution adjustment pH5.72 of 0.1N, add 6 grams of medicinal carbons and keep 25 minutes, de-charcoal circulation, inject with water standardize solution to ormal weight, uniform stirring, and keep 15 minutes, de-charcoal circulation, again by coarse filtration liquid through the continuous fine straining of 0.45um, 0.22um micropore filter element, conform with the regulations to visible foreign matters, after survey semi-finished product are qualified, under nitrogen current protection, fine straining liquid is filled in infusion bottle, every bottle of 100ml or 250ml or 500ml, jumps a queue, gland, rolls aluminium lid, in 115 DEG C of sterilizing 30min, lamp inspection, obtains the medicine composition injection containing 18 seed amino acids of the present invention.

The preparation of embodiment 19, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 20.0 grams; Serine 20.0 grams; ALANINE 40.0 grams; ILE 99.5 grams; L-Leu 117.6 grams; Aspartic Acid 60.0 grams; TYR 6.0 grams; Pidolidone 18.0 grams; L-Phe 100.0 grams; Arginine 110.23 grams; L-lysine acetate 136.5 grams; Valine 100.4 grams; L-threonine 70.0 grams; L-histidine monohydrochloride 70.0 grams; L-Trp 24.6 grams; Methionine 45.0 grams; CYSTINE 2.9 grams; Glycine 210.4 grams; Sorbitol 550.00 grams; Sodium sulfite 2.0 grams; Citric acid 2 grams; Sodium citrate 3 grams;

Prepared by the preparation method with reference to embodiment 16, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.

The preparation of embodiment 20, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 2.40 grams; Serine 2.40 grams; ALANINE 4.80 grams; ILE 8.45 grams; L-Leu 11.76 grams; L-ASPARTIC ACID 6.00 grams; TYR 0.60 gram; Pidolidone 1.80 grams; L-Phe 12.80 grams; Arginine hydrochloride or L-arginine hydrochloride 12.00 grams; L-lysine acetate 11.65 grams; Valine 8.64 grams; L-threonine 6.00 grams; L-Histidine 4.44 grams; L-Trp 2.16 grams; Methionine 5.40 grams; CYSTINE 0.24 gram; Glycine 18.24 grams; Xylitol 520 grams;

Preparation: prepared by the preparation method with reference to embodiment 16, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.

The preparation of embodiment 21, Amino Acid Compound Injection (18AA), prescription:

Proline 24.0 grams; Serine 24.0 grams; Alanine 48.0 grams; Isoleucine 84.5 grams; Leucine 117.6 grams; Aspartic Acid 60.0 grams; 6.0 grams, tyrosine; 18.0 grams, glutamic acid; Phenylalanine 128.0 grams; Arginine 99.23 grams; Lysine acetate 116.5 grams; Valine 86.4 grams; Threonine 60.0 grams; Histidine 44.4 grams; Tryptophan 21.6 grams; Methionine 54.0 grams; Cystine 2.4 grams; Glycine 182.4 grams; Sorbitol 500.00 grams; Sodium sulfite 5.0 grams;

Preparation: prepared by the preparation method with reference to embodiment 16, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.

The preparation of embodiment 22, Amino Acid Compound Injection (18AA), prescription:

Proline 24.0 grams; Serine 24.0 grams; Alanine 48.0 grams; Isoleucine 84.5 grams; Leucine 117.6 grams; Aspartic Acid 60.0 grams; 6.0 grams, tyrosine; 18.0 grams, glutamic acid; Phenylalanine 128.0 grams; Arginine 99.23 grams; Lysine acetate 116.5 grams; Valine 86.4 grams; Threonine 60.0 grams; Histidine 44.4 grams; Tryptophan 21.6 grams; Methionine 54.0 grams; Cystine 2.4 grams; Glycine 182.4 grams; Sorbitol 500.00 grams; Sodium sulfite 5.0 grams;

Preparation: prepared by the preparation method with reference to embodiment 16, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.

The preparation of embodiment 23, Amino Acid Compound Injection (18AA), prescription:

L-PROLINE 10.00 grams; Serine 10.00 grams; ALANINE 20.00 grams; ILE 35.2 grams; L-Leu 49.0 grams; L-ASPARTIC ACID 25.0 grams; TYR 2.50 grams; Pidolidone 7.5 grams; L-Phe 53.30 grams; L-arginine 41.35 grams; L-lysine acetate 48.55 grams; Valine 36.0 grams; L-threonine 25.0 grams; L-Histidine 18.5 grams; L-Trp 9.0 grams; Methionine 22.5 grams; CYSTINE 1.0 grams; Glycine 76.0 grams; D-glucitol 500.0 grams; Sodium sulfite 4.0 grams;

Preparation: prepared by the preparation method with reference to embodiment 1, obtain the transfusion of Amino Acid Compound Injection (18AA) pharmaceutical composition.Each amino acid whose content in the pharmaceutical composition of the present invention adopting amino-acid analyzer mensuration room temperature to keep sample 3 months, find all in the scope of prescription labelled amount 80-120%, in addition, after testing, find that the character, visible foreign matters, light transmittance, pH value, endotoxin etc. of solution all meet the regulation of 2010 editions Chinese Pharmacopoeia enlarged editions.

Embodiment 23

Pharmacological experiment of the present invention is as follows:

Get the Wistar male rat 24 of healthy adult, body weight 190 ~ 230g, is divided into six groups at random: Normal group, model group, positive drug control group, each group of medicine of the present invention (three groups), often organizes four.Positive drug control group and medicine of the present invention are respectively organized and are raised drink 0.28mol/LNHC1 (535mg/kg respectively, deionized water is prepared) one day, average mark gives [list of references: Yuan Yuan 2 times, Deng, China's anesthesiology magazine, 2008,28 (6): 530-533, and this article pertinent literature], all the other two matched groups raise drink deionized water.Except Normal group, all the other each group with after 1% pentobarbital sodium (0.4ml/100g) intraperitoneal injection of anesthesia rat, back cropping, iodine tincture and alcohol disinfecting, then longitudinally cut the wound of long 8cm along back, simultaneously subcutaneously in buttocks both sides cut off the muscle accounting for its body weight 1%, and the 1 piece of polrvinyl chloride sponge of heeling-in immediately, sew up wound, simultaneously row Central catheterization art, whole operation process follows sterile working.Then, postoperative Normal group and model group give all to feed to without nitrogen feedstuff respectively, freely drink water; Marketed drugs matched group gives commercially available Amino Acid Compound Injection 18AA (Guangzhou Baite Jiaoguang Medical Product Co., Ltd); Medicine group of the present invention: adopt the drug combination preparation of the embodiment of the present invention (standby by embodiment 1 method, embodiment 2 method, embodiment 3 legal system respectively) intravenously administrable, each administration group and positive controls every rat amount of infusion every day are 70ml/kg, each treated animal all feed give without nitrogen feedstuff, freely drink water, continuous 7 days.Get blood plasma, low-temperature centrifugation, the centrifugal 10min of 3000r/min, abandon precipitation, get serum, by commercially available SOD, the description method of MDA corresponding reagent box, measure after modeling respectively and the SOD of successive administration after seven days in blood plasma, [MDA measures test kit and SOD measures test kit for MDA content or activity, the product of Bioengineering Research Institute is built up in Nanjing], [disposal of experiment and animal and administration, sample and material processed, the list of references of the mensuration of MDA and SOD etc. comprises: 1, Han Hui, Deng, Chengdu University of Traditional Chinese Medicine's journal, 2009, 32 (1): 76-78, 90), 2, " Pharmacological Test Method " third edition, Xu Shuyun, etc., chief editor, People's Health Publisher, 2002 years, 3, Yuan Yuan, etc., Chinese anesthesiology magazine, 2008,28 (6): 530-533, and this article pertinent literature, ], the results are shown in Table 1.

The impact (n=4) of MDA, SOD in each rat blood before and after wound respectively formed by table 1.

Malonaldehyde (MDA) is one of end product of lipid hyperoxygen, and its concentration can reflect membrane lipid peroxidatio degree; Oxygen-derived free radicals not only causes cell injury by the peroxidating of polyunsaturated fatty acid in biomembrane, but also the degree of cell injury is caused by the catabolite of lipid peroxide, sudismase (SOD) is oxygen free radical scavenger important in body; Malonaldehyde (MDA) and sudismase (SOD) are all the sensitive indicators evaluating body oxidative stress, in blood, MDA obviously raises and the decline of SOD content, obvious oxidativestress damage is there is in prompting blood and organ, the oxidativestress damage caused due to oxygen-derived free radicals is one of important pathogenesis of multiple organ dysfunction etc. after acidosis, severe trauma, being aided with free radical scavenger in early days in liquid resuscitation to maintain organ function, is the important content of control wound shock etc.In addition, MDA and SOD all has similar reaction in burn, the damage of scald, ischemic injuries, chemotherapy, liver cirrhosis, shock, heart failure, numerous process such as poisoning, and therefore, in the above-mentioned disease of prevention and therapy, pharmaceutical composition of the present invention has respective value.

Experiment shows, the rat body weight of Normal group becomes increase trend, but for trauma in rat, the rat body weight of model group is all decline situation, and positive controls and the present invention are controlled when administration seven days substantially by the rat body weight decline situation of reagent group.Result shows, and higher than Normal group, (P<0.01, SOD content is starkly lower than Normal group (P<0.01) to the MDA content of the single rat of model group or whole group; Each administration group MDA content is starkly lower than model group (P<0.01), and SOD is active in model group (P<0.01) and positive controls (P<0.05); The MDA content of the single sample of pharmaceutical composition group of the present invention is lower than positive control, and the SOD of single sample is active in positive controls; Pharmaceutical composition group MDA content of the present invention is starkly lower than positive controls (P<0.05), and pharmaceutical composition group SOD of the present invention is active in positive controls (P<0.05); This shows that composition medicine of the present invention can alleviate the generation of MDA in blood after on rear acidosis and bed, increases the activity of SOD, and this illustrates that medicine of the present invention has corresponding more excellent value to wound and the acidosic treatment that may occur or prevention.

Embodiment 24

The pharmaceutical composition safety testing result of Amino Acid Compound Injection of the present invention (18AA)

One, the pharmaceutical composition anaphylaxis test of Amino Acid Compound Injection of the present invention (18AA)

1, test objective

The pharmaceutical composition observing Amino Acid Compound Injection of the present invention (18AA) through Formulations for systemic administration with or without sensitization.

2, test material

2.1. animal subject: adult healthy albino guinea-pig, male, body weight 200-300g.

2.2. tested material: the pharmaceutical composition of Amino Acid Compound Injection of the present invention (18AA).

2.3. contrast medicine: ovalbumin, be diluted with distilled water into 5% ovalbumin before use for subsequent use.

3, test method

3.1. sensitization contact: get Cavia porcellus 32, be divided into 4 groups at random, is respectively Vehicle controls group, test medicine group and positive controls.Often organize 8 animals.The medicinal composition solution (embodiment 1, embodiment 2 legal system are standby) of capacity (0.5ml) 0.9% sodium chloride solutions such as each treated animal difference lumbar injection (ip), 18 seed amino acids of the present invention and 5% ovalbumin, the next day once, continuous 5 times.

3.2. provocative test: each treated animal is carried out excitability injection in the 12nd day after the administration of last sensitization.Vehicle controls group, test medicine group and positive controls Cavia porcellus are respectively through medicinal composition solution and the 5% ovalbumin 1ml of jugular vein 0.9% sodium chloride solution, Amino Acid Compound Injection of the present invention (18AA).Observe and at once to 15 after recording administration, 30,60,120 and 180min in animal have but symptoms of allergic.

4, result of the test

After the medicinal composition solution of Cavia porcellus abdominal cavity sensitizing injection 0.9% sodium chloride solution, 18 seed amino acids of the present invention and 5% ovalbumin sensitization, animal ordinary circumstance is good, diet, urinate and faecal condition normal.Animal carries out excitability injection in the 12nd day after the administration of last sensitization.At once to 15 after Vehicle controls group and test medicine treated animal excite administration, 30,60,120 and 180min in be showed no cough, roll up, the symptoms of allergic such as perpendicular hair, dyspnea are even dead, therefore be evaluated as anaphylaxis feminine gender.The phenomenons such as positive controls Cavia porcellus occurs after exciting administration that spasm is twitched all immediately, pants, dyspnea and cyanosis, and dead in 5min in exciting after administration, and anaphylaxis is the extremely strong positive, in table 2.

The pharmaceutical composition of table 2 18 seed amino acids of the present invention causes Cavia porcellus anaphylaxis and degree thereof

5, conclusion (of pressure testing)

The pharmaceutical composition of Cavia porcellus intravenous injection Amino Acid Compound Injection of the present invention (18AA), does not observe animal and coughs, rolls up, erects the anaphylaxis such as hair, dyspnea phenomenon.Show the pharmaceutical composition of 18 seed amino acids of the present invention to animal subject without sensitization.

Two, the pharmaceutical composition hemolytic reaction test of Amino Acid Compound Injection of the present invention (18AA)

1, test objective: the pharmaceutical composition observing Amino Acid Compound Injection (18AA) joins in red blood cell suspension whether produce haemolysis and hemagglutination.

2, test material

Test medicine: the pharmaceutical composition of Amino Acid Compound Injection of the present invention (18AA)

3, test method

3.1.2% red blood cell suspension preparation: get healthy human blood 6ml, anticoagulant heparin, constantly stirs blood with Glass rod.Add the normal saline of about 10 times amount, shake up, the centrifugal 15min of 1500rpm, removes supernatant, the erythrocyte of precipitation again with normal saline cyclic washing 3 ~ 4 times as stated above, to the aobvious redness of supernatant.Gained erythrocyte normal saline is made into the suspension of 2%, is for experiment.

3.2. test method: get clean tube 7, be numbered, No. 1-5 pipe is test sample pipe, and No. 6 pipes are negative control pipe, and No. 7 pipes are positive control pipe.By adding 2% red blood cell suspension 2.5ml and different volume of saline shown in table 4 successively, mixing, after 37 DEG C ± 0.5 DEG C incubation half an hour, 1-5 pipe adds the medicinal composition solution of not isometric Amino Acid Compound Injection of the present invention (18AA), 6th pipe adds normal saline 2.5ml, 7th pipe adds distilled water 2.5ml, after mixing, puts 37 DEG C ± 0.5 DEG C incubation immediately.Within 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours and 3 hours, respectively observe once.If solution is in clear and bright redness, at the bottom of pipe without or have a small amount of erythrocyte to remain, show have haemolysis to occur; If have brownish red or rufous flocculent deposit in solution, do not disperse after jolting, then further cell agglutination phenomenon is judged again.

4, result of the test

The results are shown in following table 3.Visible 1 ~ 5 pipe supernatant in observed 3 hours is all colourless bright, and without floccule.7th pipe solution is clear and bright redness, represents that positive control pipe has haemolysis to produce.

The pharmaceutical composition of table 318 seed amino acid is to the effect of human red blood cell suspension

5, conclusion (of pressure testing)

Pharmaceutical composition 0.1 ~ the 0.5ml of Amino Acid Compound Injection of the present invention (18AA) joins in 2% human red blood cell suspension, Continuous Observation 3 hours, there is haemolysis and hemagglutination in each Guan Junwei of result, shows that this medicine is without hemolytic reaction and hemagglutination.

Three, the pharmaceutical composition intravascular injection irritation test of Amino Acid Compound Injection (18AA)

1, test objective

Observe animal after the pharmaceutical composition of intravenous drip Amino Acid Compound Injection (18AA), the vascular stimulation response situation of generation.

2, test material

2.1. animal: the white Female rabbits of the large ear of adult healthy New Zealand, body weight 2.0 ~ 2.5kg.

2.2. tested material: the pharmaceutical composition of Amino Acid Compound Injection (18AA).

3, test method

Female rabbits 4.Do not use any medicine for 1st, make blank parallel control and observe.Another 3 medicinal composition solutions in auris dextra edge intravenous drip Amino Acid Compound Injection (18AA) (embodiment 1), drip velocity is 20 ~ 30/min; Left auricular vein gives to wait capacity 0.9% sodium chloride solution to compare, and drip velocity is identical with by reagent.Once a day, continuous drip 5 days.During instillation, every day, the irritative response of auricular vein was observed in naked eyes timing.Within 7th day, put to death rabbit, draw materials apart from 1.0cm ~ 1.5cm place, injection site at bilateral auricular vein proximal part, fix with formaldehyde, do conventional organization section, carry out pathological examination.

4, result of the test

4.1. naked eyes result: blood vessel lines is clear, has no the congestion of blood vessel rubescent, the inflammatory reactions such as peripheral tissue edema.

4.2. pathological examination:

Blank group: see under mirror that venous blood tube chamber is complete, have no narrow, its tube wall has no inflammatory cell infiltration.

Test medicine group of the present invention: see that venous blood tube chamber is complete under (right auricular vein, the medicinal composition solution of instillation Amino Acid Compound Injection (18AA)) mirror, its tube wall is shown in a little inflammatory cell infiltration.More than have no obvious pathological changes.

Normal saline group: see that venous blood tube chamber is complete under (left auricular vein, instil 0.9% sodium chloride solution) mirror, its tube wall is shown in a little inflammatory cell infiltration.More than have no obvious pathological changes.

5, conclusion (of pressure testing)

Rabbit auricular vein instiled the medicinal composition solution of Amino Acid Compound Injection of the present invention (18AA) after 5 days, and injection site is without finding of naked eye irritative response.Microscopic pathology check result shows, have no blood vessel structure exception, endothelial injury, thrombosis and other pathological change, this result is consistent with Vehicle controls group.Prompting: the pharmaceutical composition of Amino Acid Compound Injection (18AA) to blood vessel without obvious irritation.

This research Late Cambrian: Cavia porcellus intravenous injection medicinal composition solution of the present invention, do not observe animal to cough, roll up, erect the anaphylaxis such as hair, dyspnea phenomenon, show the pharmaceutical composition of Amino Acid Compound Injection (18AA) to animal subject without sensitization.Medicinal composition solution of the present invention to people without hemolytic reaction and hemagglutination.Rabbit auricular vein continuous drip pharmaceutical composition of the present invention, continuous drip five days, to the basic nonirritant of blood vessel, proves that medicinal composition solution of the present invention can intravenously administrable, for prevention or the treatment of relevant disease.

Industrial applicibility and explanation thereof:

Below through the specific embodiment and the embodiment to invention has been detailed description, but should understand, these explanations do not form any restriction to scope of the present invention, in the case of without departing from the spirit and scope of protection of the present invention, can carry out multiple modification, improvement and replacement to technical solutions and their implementation methods of the present invention, these are all because falling within the scope of protection of the present invention; Be appreciated that the change of a lot of details is possible, therefore this do not limit the scope of the invention and spirit, and the present invention is not limited to above-described embodiment.

Claims (11)

1. the pharmaceutical composition of Amino Acid Compound Injection 18AA, is characterized in that: in every 1000ml containing principal agent component be:

Pharmaceutical composition 1, containing principal agent component in every 1000ml:

Proline or L-PROLINE 0.80-1.20 gram;

Serine or Serine 0.80-1.20 gram;

Alanine or ALANINE 1.60-2.40 gram;

Isoleucine or ILE 2.816-4.23 gram;

Leucine or L-Leu 3.92-5.88 gram;

Aspartic Acid or L-ASPARTIC ACID 2.00-3.00 gram;

Tyrosine or TYR 0.20-0.30 gram;

Glutamic acid or Pidolidone 0.60-0.90 gram;

Phenylalanine or L-Phe 4.26-6.40 gram;

Arginine or L-arginine 3.31-4.96 gram, or Arginine acetate. or L-Arginine acetate. 4.45-6.68 gram;

Lysine acetate 3.89-5.83 gram or lysine 2.76-4.14 gram, or L-lysine acetate 3.89-5.83 gram or 1B 2.76-4.14 gram;

Valine or Valine 2.88-4.32 gram;

Threonine or L-threonine 2.00-3.00 gram;

Histidine or L-Histidine 1.48-2.23 gram;

Tryptophan or L-Trp 0.72-1.08 gram;

Methionine or METHIONINE 1.80-2.70 gram;

Cystine or CYSTINE 0.08-0.12 gram;

Glycine 6.08-9.12 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Or pharmaceutical composition 2, containing principal agent component in every 1000ml:

Proline or L-PROLINE 0.80-1.20 gram;

Serine or Serine 0.80-1.20 gram;

Alanine or ALANINE 1.60-2.40 gram;

Isoleucine or ILE 2.82-4.23 gram;

Leucine or L-Leu 3.92-5.88 gram;

Aspartic Acid or L-ASPARTIC ACID 2.00-3.00 gram;

Tyrosine or TYR 0.20-0.30 gram;

Glutamic acid or Pidolidone 0.60-0.90 gram;

Phenylalanine or L-Phe 4.26-6.40 gram;

Arginine or L-arginine 3.31-4.96 gram, or Arginine acetate. or L-Arginine acetate. 4.45-6.68 gram;

Lysine acetate 3.89-5.83 gram or lysine 2.76-4.14 gram, or L-lysine acetate 3.89-5.83 gram or 1B 2.76-4.14 gram, or lysine hydrochloride or LYS 3.44-5.16 gram;

Valine or Valine 2.88-4.32 gram;

Threonine or L-threonine 2.00-3.00 gram;

Histidine hydrochloride or L-Histidine hydrochlorate (C ₆h ₉n ₃o ₂hClH ₂o) 2.00-3.00 gram;

Tryptophan or L-Trp 0.72-1.08 gram;

Methionine or METHIONINE 1.80-2.70 gram;

Cystine or CYSTINE 0.08-0.12 gram;

Glycine 6.08-9.12 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Or pharmaceutical composition 3, containing principal agent component in every 1000ml:

Proline or L-PROLINE 0.80-1.20 gram;

Serine or Serine 0.80-1.20 gram;

Alanine or ALANINE 1.60-2.40 gram;

Isoleucine or ILE 2.82-4.23 gram;

Leucine or L-Leu 3.92-5.88 gram;

Aspartic Acid or L-ASPARTIC ACID 2.00-3.00 gram;

Tyrosine or TYR 0.20-0.30 gram;

Glutamic acid or Pidolidone 0.60-0.90 gram;

Phenylalanine or L-Phe 4.26-6.40 gram;

Arginine hydrochloride or L-arginine hydrochloride 4.00-6.00 gram;

Lysine acetate 3.89-5.83 gram or lysine 2.76-4.14 gram, or L-lysine acetate 3.89-5.83 gram or 1B 2.76-4.14 gram;

Valine or Valine 2.88-4.32 gram;

Threonine or L-threonine 2.00-3.00 gram;

Histidine hydrochloride or L-Histidine hydrochlorate (C ₆h ₉n ₃o ₂hClH ₂o) 2.00-3.00 gram;

Tryptophan or L-Trp 0.72-1.08 gram;

Methionine or METHIONINE 1.80-2.70 gram;

Cystine or CYSTINE 0.08-0.12 gram;

Glycine 6.08-9.12 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Or pharmaceutical composition 4, containing principal agent component in every 1000ml:

Proline or L-PROLINE 0.80-1.20 gram;

Serine or Serine 0.80-1.20 gram;

Alanine or ALANINE 1.60-2.40 gram;

Isoleucine or ILE 2.82-4.23 gram;

Leucine or L-Leu 3.92-5.88 gram;

Aspartic Acid or L-ASPARTIC ACID 2.00-3.00 gram;

Tyrosine or TYR 0.20-0.30 gram;

Glutamic acid or Pidolidone 0.60-0.90 gram;

Phenylalanine or L-Phe 4.26-6.40 gram;

Arginine hydrochloride or L-arginine hydrochloride 4.00-6.00 gram;

Lysine acetate 3.89-5.83 gram, or lysine 2.76-4.14 gram, or L-lysine acetate 3.89-5.83 gram or 1B 2.76-4.14 gram;

Valine or Valine 2.88-4.32 gram;

Threonine or L-threonine 2.00-3.00 gram;

Histidine or L-Histidine 1.48-2.22 gram;

Tryptophan or L-Trp 0.72-1.08 gram;

Methionine or METHIONINE 1.80-2.70 gram;

Cystine or CYSTINE 0.08-0.12 gram;

Glycine 6.08-9.12 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Or pharmaceutical composition 5, containing principal agent component in every 1000ml:

Proline or L-PROLINE 1.92-2.88 gram;

Serine or Serine 1.92-2.88 gram;

Alanine or ALANINE 3.84-5.76 gram;

Isoleucine or ILE 6.76-10.14 gram;

Leucine or L-Leu 9.408-14.12 gram;

Aspartic Acid or L-ASPARTIC ACID 4.80-7.20 gram;

Tyrosine or TYR 0.48-0.72 gram;

Glutamic acid or Pidolidone 1.44-2.16 gram;

Phenylalanine or L-Phe 10.24-15.36 gram;

Arginine or L-arginine 7.938-11.91 gram, or Arginine acetate. or L-Arginine acetate. 10.67-16.02 gram;

Lysine acetate 9.32-13.40 gram or lysine 6.61-9.92 gram, or L-lysine acetate 9.33-14.00 gram or 1B 6.61-9.92 gram;

Valine or Valine 6.91-10.37 gram;

Threonine or L-threonine 4.80-7.20 gram;

Histidine or L-Histidine 3.55-5.33 gram, or histidine hydrochloride or L-Histidine hydrochlorate 4.80-7.20 gram;

Tryptophan or L-Trp 1.73-2.60 gram;

Methionine or METHIONINE 4.32-6.48 gram;

Cystine or CYSTINE 0.19-0.29 gram;

Glycine 14.59-21.89 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Or pharmaceutical composition 6, containing principal agent component in every 1000ml:

Proline or L-PROLINE 1.92-2.88 gram;

Serine or Serine 1.92-2.88 gram;

Alanine or ALANINE 3.84-5.76 gram;

Isoleucine or ILE 6.76-10.14 gram;

Leucine or L-Leu 9.41-14.12 gram;

Aspartic Acid or L-ASPARTIC ACID 4.80-7.20 gram;

Tyrosine or TYR 0.48-0.72 gram;

Glutamic acid or Pidolidone 1.44-2.16 gram;

Phenylalanine or L-Phe 10.24-15.36 gram;

Arginine hydrochloride or L-arginine hydrochloride 9.60-14.4 gram;

Lysine acetate 9.33-14.00 gram or lysine 6.61-9.92 gram, or L-lysine acetate 9.33-14.00 gram or 1B 6.61-9.92 gram;

Valine or Valine 6.92-10.37 gram;

Threonine or L-threonine 4.80-7.20 gram;

Histidine or L-Histidine 3.56-5.33 gram, or histidine hydrochloride or L-Histidine hydrochlorate 4.80-7.20 gram;

Tryptophan or L-Trp 1.73-2.60 gram;

Methionine or METHIONINE 4.32-6.48 gram;

Cystine or CYSTINE 0.19-0.29 gram;

Glycine 14.59-21.89 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram;

Or pharmaceutical composition 7, containing principal agent component in every 1000ml:

Proline or L-PROLINE 1.92-2.88 gram;

Serine or Serine 1.92-2.88 gram;

Alanine or ALANINE 3.84-5.76 gram;

Isoleucine or ILE 6.76-10.14 gram;

Leucine or L-Leu 9.41-14.12 gram;

Aspartic Acid or L-ASPARTIC ACID 4.80-7.20 gram;

Tyrosine or TYR 0.48-0.72 gram;

Glutamic acid or Pidolidone 1.44-2.16 gram;

Phenylalanine or L-Phe 10.24-15.36 gram

Arginine hydrochloride or L-arginine hydrochloride 9.60-14.4 gram;

Lysine hydrochloride or LYS 8.26-12.39 gram;

Valine or Valine 6.92-10.37 gram;

Threonine or L-threonine 4.80-7.20 gram;

Histidine or L-Histidine 3.56-5.33 gram;

Tryptophan or L-Trp 1.73-2.60 gram;

Methionine or METHIONINE 4.32-6.48 gram;

Cystine or CYSTINE 0.19-0.29 gram;

Glycine 14.59-21.89 gram;

Sorbitol or xylitol or mannitol or xylose or glucose or fructose 45-55 gram.

2. the pharmaceutical composition of Amino Acid Compound Injection 18AA according to claim 1, is characterized in that, containing component in every 1000ml:

Proline or L-PROLINE 1.00 grams;

Serine or Serine 1.00 grams;

Alanine or ALANINE 2.00 grams;

Isoleucine or ILE 3.52 grams;

Leucine or L-Leu 4.90 grams;

Aspartic Acid or L-ASPARTIC ACID 2.50 grams;

Tyrosine or TYR 0.25 gram;

Glutamic acid or Pidolidone 0.75 gram;

Phenylalanine or L-Phe 5.33 grams;

Arginine or L-arginine 4.135 grams, or Arginine acetate. or L-Arginine acetate. 5.56 grams;

Lysine acetate or L-lysine acetate 4.855 grams, or lysine or 1B 3.45g;

Valine or Valine 3.60 grams;

Threonine or L-threonine 2.50 grams;

Histidine or L-Histidine 1.85 grams;

Tryptophan or L-Trp 0.90 gram;

Methionine or METHIONINE 2.25 grams;

Cystine or CYSTINE 0.10 gram;

Glycine 7.60 grams;

Sorbitol or xylitol or 50.00 grams, mannitol.

3. the pharmaceutical composition of Amino Acid Compound Injection 18AA according to claim 1, is characterized in that, containing component in every 1000ml:

Proline or L-PROLINE 1.00 grams;

Serine or Serine 1.00 grams;

Alanine or ALANINE 2.00 grams;

Isoleucine or ILE 3.52 grams;

Leucine or L-Leu 4.90 grams;

Aspartic Acid or L-ASPARTIC ACID 2.50 grams;

Tyrosine or TYR 0.25 gram;

Glutamic acid or Pidolidone 0.75 gram;

Phenylalanine or L-Phe 5.33 grams;

Arginine or L-arginine 4.135 grams, or Arginine acetate. or L-Arginine acetate. 5.56 grams;

Lysine acetate or L-lysine acetate 4.855 grams, or lysine or 1B 3.45g;

Valine or Valine 3.60 grams;

Threonine or L-threonine 2.50 grams;

Histidine hydrochloride or L-Histidine hydrochlorate 2.50g gram;

Tryptophan or L-Trp 0.90 gram;

Methionine or METHIONINE 2.25 grams;

Cystine or CYSTINE 0.10 gram;

Glycine 7.60 grams;

Sorbitol or xylitol or 50.00 grams, mannitol.

4. the pharmaceutical composition of Amino Acid Compound Injection 18AA according to claim 1, is characterized in that, containing principal agent component in every 1000ml:

Proline or L-PROLINE 2.40 grams;

Serine or Serine 2.40 grams;

Alanine or ALANINE 4.80 grams;

Isoleucine or ILE 8.45 grams;

Leucine or L-Leu 11.76 grams;

Aspartic Acid or L-ASPARTIC ACID 6.00 grams;

Tyrosine or TYR 0.60 gram;

Glutamic acid or Pidolidone 1.80 grams;

Phenylalanine or L-Phe 12.80 grams;

Arginine or L-arginine 9.923 grams;

Lysine acetate 11.65 grams or lysine 8.26 grams, or L-lysine acetate 11.65 grams or 1B or 8.26 grams;

Valine or Valine 8.64 grams;

Threonine or L-threonine 6.00 grams;

Histidine or L-Histidine 4.44 grams;

Tryptophan or L-Trp 2.16 grams;

Methionine or METHIONINE 5.40 grams;

Cystine or CYSTINE 0.24 gram;

Glycine 18.24 grams;

Sorbitol or xylitol or mannitol or xylose or glucose or 50 grams, fructose.

5. the pharmaceutical composition of Amino Acid Compound Injection 18AA according to claim 1, is characterized in that, containing principal agent component in every 1000ml:

Proline or L-PROLINE 2.40 grams;

Serine or Serine 2.40 grams;

Alanine or ALANINE 4.80 grams;

Isoleucine or ILE 8.45 grams;

Leucine or L-Leu 11.76 grams;

Aspartic Acid or L-ASPARTIC ACID 6.00 grams;

Tyrosine or TYR 0.60 gram;

Glutamic acid or Pidolidone 1.80 grams;

Phenylalanine or L-Phe 12.80 grams;

Arginine or L-arginine 9.923 grams;

Lysine acetate 11.65 grams or lysine 8.26 grams, or L-lysine acetate 11.65 grams or 1B 8.26 grams;

Valine or Valine 8.64 grams;

Threonine or L-threonine 6.00 grams;

Histidine hydrochloride or L-Histidine hydrochlorate 6.00 grams;

Tryptophan or L-Trp 2.16 grams;

Methionine or METHIONINE 5.40 grams;

Cystine or CYSTINE 0.24 gram;

Glycine 18.24 grams;

Sorbitol or xylitol or mannitol or xylose or glucose or 50 grams, fructose.

6. the pharmaceutical composition of Amino Acid Compound Injection 18AA according to claim 1, is characterized in that, containing component in every 1000ml:

Proline or L-PROLINE 2.40 grams;

Serine or Serine 2.40 grams;

Alanine or ALANINE 4.80 grams;

Isoleucine or ILE 8.45 grams;

Leucine or L-Leu 11.76 grams;

Aspartic Acid or L-ASPARTIC ACID 6.00 grams;

Tyrosine or TYR 0.60 gram;

Glutamic acid or Pidolidone 1.80 grams;

Phenylalanine or L-Phe 12.80 grams;

Arginine hydrochloride or L-arginine hydrochloride 12.00 grams;

Lysine acetate 11.65 grams or lysine 8.26 grams, or L-lysine acetate 11.65 grams or 1B 8.26 grams;

Valine or Valine 8.64 grams;

Threonine or L-threonine 6.00 grams;

Histidine or L-Histidine 4.44 grams, or histidine hydrochloride or L-Histidine hydrochlorate 6.00 grams;

Tryptophan or L-Trp 2.16 grams;

Methionine or METHIONINE 5.40 grams;

Cystine or CYSTINE 0.24 gram;

Glycine 18.24 grams;

Sorbitol or xylitol or mannitol or xylose or glucose or 50 grams, fructose.

7. the pharmaceutical composition of the Amino Acid Compound Injection 18AA in claim 1 to 6 described in arbitrary power requirement, it is characterized in that: this pharmaceutical composition can contain pharmaceutically acceptable antioxidant or stabilizing agent, pharmaceutically acceptable antioxidant or stabilizing agent are selected from: tartaric acid or its salt pharmaceutically accepted, malic acid or its salt pharmaceutically accepted, citric acid or its salt pharmaceutically accepted, repeatedly fragrant, sodium sulfite, or sodium pyrosulfite, sodium ethylene diamine tetracetate calcium, disodiumedetate, ethylenediaminetetraacetic acid, aminotriacetic acid, diethylene-triamine pentaacetic acid, one or more in one or more in DL-type or D-type or L-aminoacid or its salt pharmaceutically accepted or its crystalline hydrate, containing antioxidant or stabilizing agent 0 ~ 8.00g in every 1000ml injection.

8. the pharmaceutical composition of the Amino Acid Compound Injection 18AA described in requiring according to power arbitrary in claim 1 to 6, it is characterized in that, its preparation method is:

Appropriate water for injection is added in dispensing canister, heated and boiled, adopt evacuation and inflated with nitrogen replacement Treatment in process of production, reduce the content of oxygen in dispensing canister, under whole process fills nitrogen, between water temperature 96 DEG C-50 DEG C successively or segmentation drop into supplementary material: sorbitol or xylitol or mannitol or xylose or glucose or fructose, tyrosine, leucine, isoleucine, valine, methionine, phenylalanine, glutamic acid, Aspartic Acid, lysine or lysine acetate, threonine, glycine, arginine, alanine, proline, serine, cystine, histidine and tryptophan, antioxidant or stabilizing agent, be stirred to entirely molten, the pH of solution is regulated to be 5.00-7.00 with one or more solution of the appropriate pH adjusting agent pharmaceutically accepted, inject and use water standardize solution to ormal weight, add the medicinal carbon of 0.05-1% (w/v), uniform stirring, and keep 10-40 minute, de-charcoal circulation, then by coarse filtration liquid through 0.45um, 0.22um micropore filter element or the continuous fine straining of hyperfiltration process, under nitrogen current protection, fine straining liquid is filled in non-PVC multi-layer co-extruded transfusion bag or in infusion bottle, every bag or every bottle of 50ml or 100ml or 250ml or 500ml or 750ml or 1000ml, the sealing of non-PVC multi-layer co-extruded transfusion bag or infusion bottle, gland, roll aluminium lid, in 105-121 DEG C of sterilizing 5-40 minute, lamp inspection, for putting into oxygen-inhibiting agent again after non-PVC multi-layer co-extruded transfusion bag sealing and putting outer bag, sealing, obtains the pharmaceutical composition containing 18 seed amino acids of the present invention.

9. the pharmaceutical composition of the Amino Acid Compound Injection 18AA described in requiring according to power arbitrary in claim 1 to 6, it is characterized in that, the pH of the medicinal composition solution of Amino Acid Compound Injection 18AA is 5.00-7.00.

10. the pharmaceutical composition preparation method of Amino Acid Compound Injection 18AA according to claim 7, it is characterized in that, its pH adjusting agent is selected from acetic acid, phosphoric acid, citric acid, citric acid monohydrate compound, tartaric acid, lactic acid, sodium hydroxide, sodium carbonate, sodium bicarbonate, meglumine, sodium bisulfate, sodium dihydrogen phosphate, sodium hydrogen phosphate or sodium hydrogen phosphate 7 hydrate or tertiary sodium phosphate, sodium acetate, sodium lactate, sodium bitartrate, sodium tartrate, trisodium citrate or trisodium citrate 2 hydrate, or one or more in the acid pharmaceutically accepted or alkali or its crystalline hydrate, the acid pharmaceutically accepted or alkali are the lewis acid of broad sense or the lewis base of broad sense.

11. according to the pharmaceutical composition weighing the Amino Acid Compound Injection 18AA described in requiring arbitrary in claim 1 to 6, it is characterized in that, its purposes is: can not meet the application in the patient of organism metabolism needs, the nutriture improving patients after surgery and metabolic acidosis or high sodium, the prevention of hyperchloremia or the medicine for the treatment of for the preparation of aminoacid such as protein Deficiency of Intake, malabsorptions.