CN103784438B - A kind of Amino Acid Compound Injection-HBC composition and method of making the same - Google Patents

Abstract

The invention belongs to medical art, specifically disclose a kind of Amino Acid Compound Injection-HBC composition and method of making the same, containing following component in said composition: isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, tryptophan, valine, alanine, arginine, histidine, proline, serine, glycine, cysteine hydrochloride, malic acid and water for injection.Said composition is not containing sulphite kind antioxidant, malic acid is as pH value regulator, metal ion chelation agent or stabilizing agent, also can improve various amino acid whose bioavailability, cysteine hydrochloride is as antioxidant, in production process, whole process fills nitrogen, to reduce residual oxygen in product, the like product Amino Acid Compound Injection-HBC making product quality be better than having gone on the market, Clinical practice is safer.

Description

A kind of Amino Acid Compound Injection-HBC composition and method of making the same

Technical field

The invention belongs to medical art, more specifically relate to a kind of Amino Acid Compound Injection (15-HBC) compositions, also relate to the preparation method of a kind of Amino Acid Compound Injection (15-HBC) compositions simultaneously.The present invention is applicable to can not be oral or through intestinal supply nutrition, and the patient that nutrition can not be satisfied the demand, can this compositions of venoclysis to meet the needs of body synthetic protein, hyperfunction for muscle catabolism under the stress state such as large-area burns, wound and severe infections, digestive system function obstacle, the nutritional support of nutrition deterioration and immunologic function degression patient, and for the improvement of patients after surgery nutrition.

Background technology

Amino Acid Compound Injection (15-HBC) is parenteral nutrition medicine, has special consequence in clinical practice.Its prescription, according to stress wound Plasma Amine Acid feature design, is forth generation high concentration branched-chain amino acid.The first-selected nutritional preparation of various stress state and critical patient clinically now.

This product, containing the branched-chain amino acid of high concentration, can suppress the decomposition of muscle protein after patient's infusion of severe trauma, infection, stress state; When energy is in liberal supply, this product participates in the anabolism of protein, improves nitrogen balance and is beneficial to repair in trauma and infection; Under stress state, this product can provide energy, reduces fall and the negative nitrogen balance of weight in patients, is conducive to wound healing and the recovery of organ physiological function.Basic amino acid in this product adopts acetate or free alkali, and chlorinty is low, can reduce metabolic acidosis in application.Be applicable to that muscle catabolism under large-area burns and the stress state such as wound and severe infections is hyperfunction, the nutritional support of digestive system obstacle and nutrition deterioration and immuuoeorapromised host, also can be used for patients after surgery and improve nutritional status.

The aminoacid of some instability in amino acid transfusion product, as tryptophan, methionine, glutamic acid etc., under the effects such as high temperature, oxygen, metal ion, can degrade, and solution colour flavescence, amino acid content decline and related substance are increased, amino acid transfusion product clinical practice risk is increased.Amino Acid Compound Injection (15-HBC) belongs to infusion solutions product, and necessary terminal sterilization, in order to ensure the stability of product, domestic a lot of enterprise adds sodium pyrosulfite in the product as antioxidant.

But, sodium pyrosulfite is harmful to human body, has reported many untoward reaction clinically at present, and modal is sulphite allergy (especially asthma patient), symptom is bronchospasm, stridulate, dyspnea, pernicious laryngeal edema, and hypotension, shock are even dead.In addition, also have some research reports, sulphite may cause damage to chromosome and DNA, and the irreversible reaction etc. of cystine linkage in protein.

At present, nearly all Amino Acid Compound Injection (15-HBC) manufacturer all with the addition of sodium pyrosulfite in the product as antioxidant, although as used sodium pyrosulfite in " Chinese Pharmacopoeia " middle clear stipulaties injection, general concentration is 0.1% ~ 0.2%, but the risk of clinical practice still inevitably exists.

Chinese patent CN101120917A discloses a kind of not containing the Amino Acid Compound Injection of antioxidant, it is characterized in that the overall process nitrogen produced is protected.As long as thoroughly removed by the oxygen in system in theory, just can not add sulphite, be practically limited to technical conditions and oxygen content can only be reduced to low-down level.Viewed from technique disclosed in it, also there is certain leak, can achieve the goal and also there is uncertain factor.

A kind of Amino Acid Compound Injection and preparation method thereof is disclosed in Chinese patent CN102940628A; it is characterized in that not containing sulphite kind antioxidant; have employed cysteine and calcium disodium edetate as antioxidant and metal ion chelation agent, then adopt nitrogen protection in production process and realize.We find, calcium disodium edetate has stronger chelation of metal ion, although obviously can not affect blood calcium concentration, may affect other microelement concentrations in blood, make clinical application aspect there is certain risk.

A kind of compositions containing 18 seed amino acids is disclosed in Chinese patent CN101439036A; it is characterized in that not containing sulphite kind antioxidant; have employed cysteine hydrochloride and citric acid as antioxidant and metal ion chelation agent, then adopt nitrogen protection in production process and realize.We find, citric acid also has good antioxidation unlike described in patent application document, and citric acid, may with cysteine hydrochloride synergism with the stability of protected amino acid as metal ion chelation agent or stabilizing agent.

Malic acid has the chelation of metal ion same with citric acid or stabilizer function, participates in tricarboxylic acid cycle equally, and in addition, malic acid may have identical with citric acid or better physiological action: A, can improve amino acid whose bioavailability.B, cancer therapy drug can be reduced to Normocellular infringement, for the ancillary drug after cancer Radiotherapy chemotherapy.C, can promote ammonia metabolism, reduce ammonia concentration, have protective effect to liver, be treatment hepatic insufficiency, liver failure, the hepatocarcinoma especially good medicine of hyperammonemia that causes of hepatic insufficiency.D, can be used as one for the treatment of heart disease basal liquid composition, for K ⁺, Mg ²⁺supplement, keep cardiac muscle energy metabolism, the ischemic myocardium of myocardial infarction is played a protective role.E, can improve the energy metabolism of cerebral tissue, neurotransmitter in adjustment brain, is conducive to the recovery of learning and memory function, improves significantly to learning and memory.F, can be used for disease such as treatment anemia, hypoimmunity, uremia, hypertension etc.

Therefore, explore and produce not containing the Amino Acid Compound Injection of sulphite kind antioxidant, be worth research.

Summary of the invention

For the deficiencies in the prior art, first object of the present invention there are provided a kind of Amino Acid Compound Injection-HBC compositions, formula is reasonable, easy to use, this compositions, containing high concentration branched-chain amino acid, can suppress severe trauma, infection, stress state patient muscle protein to decompose, participate in protein synthesis, improve nitrogen balance, in order to repair in trauma and infection.With strong points clinically, contain the special formulation of high side chain and low aromatic amino acid (phenylalanine, tryptophan) in prescription, have the effect correcting Plasma Amine Acid disorder, to treatment hepatic coma, hepatic encephalopathy has certain effect, supplements nutrition simultaneously.Injection 15-HBC of the present invention, while guarantee product stability, thoroughly can eliminate the side effect of sulfites to human body.

Another object of the present invention is the preparation method that there are provided a kind of described Amino Acid Compound Injection-HBC compositions; easy to implement the method; easy and simple to handle, in process for preparation, omnidistance employing nitrogen protection, can suppress or alleviate unstable amino acid whose degraded effectively.After fill completes, evacuation fills pure nitrogen gas, than nitrogen mode of the filling better effects if of routine, more can reduce the residual oxygen in product.The metal ion that malic acid may be able to exist in chelate solution, reduces or suppresses the speed of metal ion catalysis amino-acid oxidase, or with the group effect on unstable aminoacid and produce stabilizer function.Instead of sodium pyrosulfite, completely eliminate its side effect to human body.The antioxidation that cysteine hydrochloride self has, can ensure the stability of product further.

In order to realize above-mentioned object, the present invention adopts following technical measures:

A kind of Amino Acid Compound Injection-HBC compositions, is characterized in that, every 1000mL injection 15-HBC compositions composed as follows:

The pH value of described injection 15-HBC compositions is 5.5 ~ 7.0.

A kind of Amino Acid Compound Injection-HBC compositions, is characterized in that, (preferable range) composed as follows of every 1000mL injection 15-HBC compositions:

The pH value of described injection 15-HBC compositions is 5.5 ~ 7.0.

A kind of Amino Acid Compound Injection-HBC compositions, is characterized in that, (the more excellent scope) composed as follows of every 1000mL injection 15-HBC compositions:

The pH value of described injection 15-HBC compositions is 5.5 ~ 7.0.

A kind of Amino Acid Compound Injection-HBC compositions, is characterized in that, (optimum formula) composed as follows of every 1000mL injection 15-HBC compositions:

The pH value of described injection 15-HBC compositions is 6.0.

A preparation method for above-mentioned each formula Amino Acid Compound Injection-HBC compositions, its step is as follows:

A, in dense preparing tank, add proper amount of fresh water for injection (accounting for injecta composition cumulative volume 60%-80%), boil (100 DEG C), pass into pure nitrogen gas, open and stir, for subsequent use, following all operations carries out all under nitrogen protection.

B, be cooled to 85 ~ 90 DEG C, add leucine, isoleucine, valine, methionine successively, stirring and dissolving.

C, be cooled to 75 ~ 80 DEG C, add phenylalanine, lysine acetate, threonine, glycine successively, stirring and dissolving.

D, be cooled to 60 ~ 65 DEG C, add arginine, alanine, proline, serine, histidine successively.

E, stir after, be cooled to 40 ~ 45 DEG C, add cysteine hydrochloride, tryptophan, malic acid, stirring and dissolving.

F, add medicinal carbon (0.05% ~ 0.2%, w/v), stirring and adsorbing 30 ~ 60 minutes.

G, solution take off charcoal through titanium rod filter circulating filtration, and pump in dilute preparing tank and add to the full amount of water for injection, intermediate mensuration is carried out in sampling, qualified rear fine straining is to clear and bright, fill is in glass infusion bottle, and evacuation fills pure nitrogen gas, controls remaining oxygen to 2% (volume fraction) below.

H, to jump a queue, roll lid, 115 ~ 121 DEG C of moist heat sterilizations 8 ~ 30 minutes, to obtain final product.

The aminoacid of some instability in amino acid transfusion product, as tryptophan, methionine, glutamic acid etc., under the effects such as high temperature, oxygen, metal ion, can degrade, and then solution colour flavescence, amino acid content decline and related substance are increased, amino acid transfusion product clinical practice risk is increased.High temperature (115 ~ 121 DEG C) sterilizing is the inevitable key production technology thereof of infusion solutions product, reduces residual oxygen and dissolved oxygen in product, and the concentration of metal ions in solution, is the effective method ensureing Amino Acid Compound Injection product quality.

Ultimate principle of the present invention is: before Amino Acid Compound Injection (compositions) preparation; pure nitrogen gas is passed into drain the dissolved oxygen in water in material-compound tank; omnidistance employing nitrogen protection in process for preparation; after fill completes; evacuation fills the residual oxygen in pure nitrogen gas control product, suppresses or alleviates unstable amino acid whose degraded.Add malic acid simultaneously, regulate solution ph on the one hand in 5.5 ~ 7.0 scopes, the metal ion that may exist in chelate solution on the other hand, reduces or suppresses the speed of metal ion catalysis amino-acid oxidase, or with the group effect on unstable aminoacid and produce stabilizer function.In addition, the antioxidation that cysteine hydrochloride self has, can ensure the stability of product further.

The present invention compared with prior art, has the following advantages and effect:

1, omnidistance employing nitrogen protection in process for preparation, can suppress or alleviate unstable amino acid whose degraded effectively.

2, after fill completes, evacuation fills pure nitrogen gas, than nitrogen mode of the filling better effects if of routine, more can reduce the residual oxygen in product.

3, the malic acid metal ion that may be able to exist in chelate solution, reduces or suppresses the speed of metal ion catalysis amino-acid oxidase, or with the group effect on unstable aminoacid and produce stabilizer function.Instead of sodium pyrosulfite, completely eliminate its side effect to human body.

4, the antioxidation that has of cysteine hydrochloride self, can ensure the stability of product further.

Detailed description of the invention

Below in conjunction with specific embodiment, product of the present invention and method are described in further detail.

Embodiment 1:

A kind of Amino Acid Compound Injection-HBC compositions, it is characterized in that, every 1000mL injecta composition is composed as follows:

The pH value of described injection 15-HBC compositions is 6.0.

The preparation method of Amino Acid Compound Injection (15-HBC) compositions of above-mentioned formula, the steps include:

A, in dense preparing tank, add 700mL fresh water for injection, boil (100 DEG C), pass into pure nitrogen gas, open and stir, for subsequent use; Following all operations carries out all under nitrogen protection.

B, be cooled to 85 or 86 or 87 or 88 or 89 or 90 DEG C, add leucine, isoleucine, valine, methionine successively, stirring and dissolving.

After C, stirring and dissolving, be cooled to 75 or 76 or 77 or 78 or 79 or 80 DEG C, add phenylalanine, lysine acetate, threonine, glycine successively, stirring and dissolving.

After D, stirring and dissolving, be cooled to 60 or 61 or 62 or 63 or 64 or 65 DEG C, add arginine, alanine, proline, serine, histidine successively.

E, stir after, be cooled to 40 or 41 or 42 or 43 or 44 or 45 DEG C, add cysteine hydrochloride, tryptophan, malic acid successively, stirring and dissolving.

F, add 767 type needle-use activated carbons (0.05 or 0.08 or 0.1 or 0.14 or 0.17 or 0.2%, w/v), stirring and adsorbing 30 or 35 or 40 or 45 or 50 or 55 or 60 minutes.

G, solution take off charcoal through titanium rod filter circulating filtration, and pump in dilute preparing tank and add to the full amount of water for injection, intermediate mensuration is carried out in sampling, qualified rear fine straining is to clear and bright, and its pH value is 6.0, and fill is in glass infusion bottle, evacuation fills pure nitrogen gas, controls below remaining oxygen to 2%.

H, to jump a queue, roll lid, 115 or 117 or 121 DEG C of moist heat sterilizations 8 or 12 or 16 or 21 or 24 or 27 or 30 minutes, obtain product.

Embodiment 2-7:

A kind of Amino Acid Compound Injection-HBC compositions, it is characterized in that, every 1000mL injecta composition is composed as follows, and for simplicity, the pH value of each compound composition writes on last column:

Component and pH

Embodiment 2

Embodiment 3

Embodiment 4

Embodiment 5

Embodiment 6

Embodiment 7

Malic acid

0.3g

2.5g

1.0g

1.3g

1.8g

2.2g

Cysteine hydrochloride

0.1g

0.4g

0.18g

0.26g

0.29g

0.33g

Isoleucine

6.66g

8.5g

6.9g

7.4g

7.9g

8.2g

Leucine

12.78g

15.0g

13.0g

13.4g

13.9g

14.5g

Lysine acetate

4.8g

7.0g

5.2g

5.9g

6.2g

6.7g

Methionine

1.5g

3.5g

1.8g

2.2g

2.9g

3.1g

Phenylalanine

2.2g

4.5g

2.5g

2.9g

3.2g

4.0g

Threonine

1.0g

3.5g

1.3g

1.9g

2.4g

3.0g

Tryptophan

0.3g

1.5g

0.5g

0.9g

1.3g

1.4g

Valine

6.86g

10.5g

7.0g

7.3g

8.1g

8.9g

Alanine

2.0g

7.0g

2.3g

2.9g

3.4g

4.0g

Arginine

4.8g

7.5g

5.2g

5.9g

6.4g

7.0g

Histidine

1.0g

2.5g

1.4g

1.8g

2.0g

2.1g

Proline

4.3g

8.5g

4.6g

5.1g

5.6g

6.4g

Serine

2.3g

4.5g

2.8g

3.1g

3.3g

4.1g

Glycine

2.3g

4.5g

2.5g

2.9g

3.6g

4.0g

Water for injection

Surplus

Surplus

Surplus

Surplus

Surplus

Surplus

PH value

6.7

5.8

6.5

6.3

6.2

6.1

Its preparation method is all identical with embodiment 1.

By following related tests, technical scheme of the present invention is described further:

One, the stability comparative test of embodiment 1 products obtained therefrom and the commercially available like product containing sodium pyrosulfite:

Embodiment 1 products obtained therefrom is test group, commercially available Amino Acid Compound Injection (15-HBC) (adds 0.02%(w/v) as a control group sodium pyrosulfite, about regulating solution ph to 6.0 with glacial acetic acid).

The prescription of the commercially available Amino Acid Compound Injection (15-HBC) containing sodium pyrosulfite is as follows:

In order to investigate the stability of test group and control sample, product is placed 10 days respectively under illumination 4500lx ± 500lx, high temperature 60 DEG C of conditions, detect respectively at sampling in the 0th, 5,10 day, measure the projects such as its character, pH value, light transmittance, visible foreign matters, amino acid content.Assay adopts high performance liquid chromatograph or FDAC amino-acid analyzer to carry out separation determination (amino acid content is sign content, all calculates according to each aminoacid input amount, is mainly used in observing changes of contents situation), the results are shown in Table 1 ~ 2.

Table 1 Amino Acid Compound Injection (15-HBC) 4500lx ± 500lx contrasts and investigates result

Result is investigated in table 2 Amino Acid Compound Injection (15-HBC) 60 DEG C contrast

As can be seen from upper watch test result, Amino Acid Compound Injection of the present invention (15-HBC) compositions and commercially available Amino Acid Compound Injection (15-HBC) investigate 10 days respectively under 4500lx ± 500lx and 60 DEG C condition, from the variation tendency of the aspects such as light transmittance, methionine, tryptophan and arginine content, the present composition is obviously stablized than commercially available product, the character of solution, pH value and other amino acid contents are without significant change, show the steady quality of injection of the present invention, and quality is better than commercially available same veriety.

Two, the safety testing (anaphylaxis, blood vessel irritation and hemolytic) of sample:

In order to investigate the safety of the present composition, for clinical research provides safety reference information, embodiment 1 products obtained therefrom, as test sample group, carries out zest, haemolysis and allergy etc. and tests to local, specific safety that Formulations for systemic administration is relevant.0.9% sodium chloride injection is as negative controls, and 20% human albumin is as positive reference substance.

Test method and result:

1, vascular stimulation tests

1.1 test method

Get adult healthy white rabbit 3, test sample group is from left ear edge slow intravenous injection 10mL/kg test sample stock solution, and auris dextra edge constant speed identical size injection penetrates sodium chloride injection.Every day is administered once, continuous 5 days.During administration, perusal administration every day local vascular is with or without thrombosis, and surrounding tissue is with or without inflammatory reactions such as red and swollen blood stasis.Put to death animal in last administration after 48 hours, get rapidly its ear tissue (from entry point centripetal direction 2 ~ 3cm), 10% formalin is fixed, paraffin embedding, conventional film-making, and HE dyes, and light Microscopic observation blood vessel and tissue morphology change.

1.2 result of the test

Perusal, has no the obviously symptom such as red, swollen, blood stasis during the administration of each group rabbit auricular vein injection site.Test sample group compares with matched group and has no obvious difference.The results are shown in Table 3.

Table 3 vascular stimulation tests visual results

Note: without thrombosis (-) microthrombus 1-4mm(+) middle thrombosis 5-14mm(++) large thrombosis (+++)

NIP change (-) mild inflammation 3cm scope (+) moderate inflammation scope 1/3 auricular concha (++)

Intensity inflammation scope 1/2 auricular concha-full ear (+++)

Histological findings: test sample and matched group to rabbit blood vessel without obvious irritation.

2, hypersensitive test

2.1 test method

Get body weight 250g ~ 350g healthy guinea pig 20, be divided at random 3 groups (test sample group, negative control group, positive controls), wherein test sample group 8, other often organize 6.Continuous 3 times, the next day lumbar injection need testing solution, sodium chloride injection and 20% human albumin 0.5mL/ only carry out sensitization.After final injection, vein on the 12nd is injected need testing solution, sodium chloride injection and 20% human albumin 1mL/ respectively and is only excited, at once to 30min after intravenous injection, by table 4, the reaction that symptom observes every Cavia porcellus is in detail described, the appearance of symptom and extinction time, the longest observation 3 hours.And the evaluation criterion of pressing table 5 evaluates anaphylaxis occurrence degree.Calculate anaphylaxis incidence rate.Comprehensive descision is carried out according to reaction incidence rate and symptoms of allergic.Must not there is anaphylaxis in negative control group Cavia porcellus, positive controls Cavia porcellus all should occur anaphylaxis.

2.2 result of the test

After test sample group and the administration of negative control group animals iv, in 30min all there is not anaphylaxis in all Cavia porcelluss of each group, after 20% human albumin's intravenously administrable all there is the symptoms such as sneeze, cough, dyspnea, instability of gait, spasm in 6 Cavia porcelluss, and have 2 Cavia porcellus death.The results are shown in Table 6.

Table 4 symptoms of allergic

Table 5 whole body sensitization evaluation criterion

Result: at the conditions of the experiments described above, there is not systemic anaphylaxis in test sample Amino Acid Compound Injection (15-HBC).

Table 6 Amino Acid Compound Injection (15-HBC) Hypersensitive tests result

3, hemolytic test

3.1 test method

Get 7, test tube, 2% erythrocyte suspension and normal saline is added successively by table 7 proportional quantity, after mixing, half an hour is placed in 37 ± 0.5 DEG C of calorstats, then 1 ~ No. 5 pipe adds the test sample stock solution of different volumes respectively, and No. 6 pipe adds normal saline for negative control pipe, manages as positive control adds water for injection for No. 7, after shaking up, put in 37 ± 0.5 DEG C of calorstats.Start to observe once every 15min, after 1 hour, observed once every 1 hour, Continuous Observation 3 hours, redness as transparent in solution, namely represents haemolysis.As there being brownish red flocculent deposit in solution, indicate erythroagglutination.

Table 7 Amino Acid Compound Injection (15-HBC) hemolytic test proportional quantity (mL)

3.2 result of the test

No. 7 pipes are at 37 DEG C of insulation 15min, namely there is haemolysis in solution, and add 1 ~ No. 5 pipe, No. 8 ~ 12, the commercially available control drug solution pipe of need testing solution, No. 6 sodium chloride injection pipe solution all not transparent redness in official hour, there is not brownish red flocculent deposit yet, show that Amino Acid Compound Injection (15-HBC) does not cause haemolysis and agglutination to rabbit erythrocyte, the results are shown in Table 8.

Table 8 Amino Acid Compound Injection (15-HBC) hemolytic test result

Test tube is numbered

No. 1 pipe

No. 2 pipes

No. 3 pipes

No. 4 pipes

No. 5 pipes

No. 6 pipes

No. 7 pipes

37 DEG C of insulation 15min

-

-

-

-

-

-

+++

37 DEG C of insulation 30min

-

-

-

-

-

-

+++

37 DEG C of insulation 45min

-

-

-

-

-

-

+++

37 DEG C of insulation 1h

-

-

-

-

-

-

+++

37 DEG C of insulation 2h

-

-

-

-

-

-

+++

37 DEG C of insulation 3h

-

-

-

-

-

-

+++

Note: +++ complete hemolysis; ++ part haemolysis; + coagulation;-not haemolysis, also there is not coagulation

Tested to local, specific safety that Formulations for systemic administration is relevant by zest, haemolysis and allergy etc., result shows to adopt the Amino Acid Compound Injection (15-HBC) of this prescription and preparation method production to rabbit vein blood vessel without obvious irritation, haemolysis and agglutination are not caused to rabbit erythrocyte, anaphylaxis be there is not to Cavia porcellus, Clinical practice safety.

Three, the study on the stability of sample:

In order to present composition steady quality is described, by Amino Acid Compound Injection (15-HBC) compositions prepared according to embodiment 1, place under room temperature condition, detect respectively at sampling in 3,6,9,12,18,24 months, measure the projects such as its character, pH value, light transmittance, visible foreign matters and amino acid content, the results are shown in Table 9.By Amino Acid Compound Injection (15-HBC) compositions prepared according to embodiment 2, place under 40 DEG C of conditions, detect respectively at sampling in 1,2,3,6 month, (amino acid content is sign content to measure the projects such as its character, pH value, light transmittance, visible foreign matters and amino acid content, all calculate according to each aminoacid input amount, be mainly used in observing changes of contents situation), the results are shown in Table 10.

Table 9 Amino Acid Compound Injection (15-HBC) room temperature keeps sample investigation result

Table 10 Amino Acid Compound Injection (15-HBC) 40 DEG C keeps sample investigation result

As can be seen from Table 9, after Amino Acid Compound Injection of the present invention (15-HBC) compositions deposits 24 months at ambient temperature, the indexs such as character, pH value, light transmittance and amino acid content are without significant change.As can be seen from Table 10, after Amino Acid Compound Injection of the present invention (15-HBC) compositions deposits 6 months under 40 DEG C of conditions, the indexs such as character, pH value, light transmittance and amino acid content, without significant change, show that present composition quality stability is better.

Specific embodiment described in this description is only to the explanation for example of the present invention's spirit.Those skilled in the art can make various amendment or supplement or adopt similar mode to substitute to described specific embodiment, but can't depart from spirit of the present invention or surmount the scope that appended claims defines.

Claims (1)

1. an Amino Acid Compound Injection-HBC compositions, is characterized in that, every 1000mL injection 15-HBC compositions composed as follows:

Raw material dosage raw material dosage

Isoleucine 7.66g, leucine 13.78g,

Lysine acetate 5.8g, methionine 2.5g,

Phenylalanine-3,4-quinone .2g, threonine 2.0g,

Tryptophan 0.9g, valine 8.86g,

Alanine 4.0g, arginine 5.8g,

Histidine 1.6g, proline 6.3g,

Serine 3.3g, glycine 3.3g,

Cysteine hydrochloride 0.2g, malic acid 2.0g,

Water for injection surplus;

The pH value of described injection 15-HBC compositions is 6.0;

The preparation method of described Amino Acid Compound Injection-HBC compositions, its step is as follows:

A, in dense preparing tank, add proper amount of fresh water for injection, boil, pass into pure nitrogen gas, open and stir, for subsequent use, following process for preparation whole process adopts nitrogen protection;

B, be cooled to 85 ~ 90 DEG C, add leucine, isoleucine, valine, methionine successively, stirring and dissolving;

C, be cooled to 75 ~ 80 DEG C, add phenylalanine, lysine acetate, threonine, glycine successively, stirring and dissolving;

D, be cooled to 60 ~ 65 DEG C, add arginine, alanine, proline, serine, histidine successively;

E, stir after, be cooled to 40 ~ 45 DEG C, add cysteine hydrochloride, tryptophan, malic acid, stirring and dissolving;

F, add 0.05% ~ 0.2% medicinal carbon, stirring and adsorbing 30 ~ 60 minutes;

G, solution take off charcoal through titanium rod filter circulating filtration, and pump in dilute preparing tank and add to the full amount of water for injection, intermediate mensuration is carried out in sampling, and qualified rear fine straining is to clear and bright, and fill is in glass infusion bottle, and evacuation fills pure nitrogen gas, controls below remaining oxygen to 2%;

H, to jump a queue, roll lid, 115 ~ 121 DEG C of moist heat sterilizations 8 ~ 30 minutes, to obtain final product.