CN103784438A

CN103784438A - Compound amino acid injection 15-HBC composition and preparation method thereof

Info

Publication number: CN103784438A
Application number: CN201410078313.9A
Authority: CN
Inventors: 李金屏; 甘周阳
Original assignee: HUBEI HALFSKY PHARMACEUTICALS CO Ltd
Current assignee: HUBEI HALFSKY PHARMACEUTICALS CO Ltd
Priority date: 2014-03-05
Filing date: 2014-03-05
Publication date: 2014-05-14
Anticipated expiration: 2034-03-05
Also published as: CN103784438B

Abstract

The invention belongs to the technical field of medicine, and particularly discloses a compound amino acid injection 15-HBC composition and a preparation method thereof. The composition contains the following components of isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, tryptophan, valine, alanine, arginine, histidine, proline, serine, glycine, cysteine hydrochloride, malic acid and water for injection. The composition does not contain sulfite-type antioxygen, the malic acid serves as a PH value conditioning agent or a metal ionchelating agent or a stabilizer and can further improve the bioavailability of various amino acids, the cysteine hydrochloride serves as antioxygen, nitrogenization is conducted in the whole production process so as to reduce residual oxygen in the product to enable the quality of the product to be superior to that of on-sale compound amino acid injection 15-HBC products of the same type, and therefore clinical use 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 technical field, 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 nutrition patient that can not satisfy 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, nutrition deterioration and immunologic function degression patient's nutritional support, 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, be the 4th 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; In the time that energy supply is sufficient, 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 organ physiological function and recovers.Basic amino acid in this product adopts acetate or free alkali, and chlorinty is low, in application, can reduce metabolic acidosis.Be applicable to that muscle catabolism under the stress state such as large-area burns and 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.

Some unsettled aminoacid 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 are declined and related substance increase, amino acid transfusion product clinical practice risk is increased.Amino Acid Compound Injection (15-HBC) belongs to infusion solutions product, necessary terminal sterilization, and in order to guarantee the stability of product, domestic a lot of enterprises add sodium pyrosulfite as antioxidant in product.

But, sodium pyrosulfite is harmful to human body, has reported clinically at present many untoward reaction, 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 has all added sodium pyrosulfite as antioxidant in product, although clearly stipulate in injection in " Chinese Pharmacopoeia " as use sodium pyrosulfite, 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 of production is protected.As long as the oxygen in system is thoroughly removed, just can not add sulphite in theory, be practically limited to technical conditions and oxygen content can only be reduced to low-down level.See and also have certain leak from its disclosed technique, can achieve the goal and also have uncertain factor.

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

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

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

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

Summary of the invention

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

Another object of the present invention is the preparation method that has been to provide a kind of described Amino Acid Compound Injection-HBC compositions; easy to implement the method; easy and simple to handle, whole process using nitrogen protection in process for preparation, can suppress or alleviate unstable amino acid whose degraded effectively.After fill completes, evacuation fills pure nitrogen gas, than the 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 exist in can chelate solution, reduces or suppresses the speed of metal ion catalysis amino-acid oxidase, or with unstable aminoacid on group effect and produce stabilizer function.Replace sodium pyrosulfite, thoroughly eliminated its side effect to human body.The antioxidation that cysteine hydrochloride self has, can further guarantee the stability of product.

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 ℃), pass into pure nitrogen gas, open and stir, for subsequent use, below all operations were all under nitrogen protection, carry out.

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

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

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

E, stir after, be cooled to 40～45 ℃, 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, through the de-charcoal of titanium rod filter circulating filtration, pump in dilute preparing tank and add to the full amount of water for injection, and 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 below remaining oxygen to 2% (volume fraction).

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

Some unsettled aminoacid 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 are declined and related substance increase, amino acid transfusion product clinical practice risk is increased.High temperature (115～121 ℃) sterilizing is the inevitable key production technology thereof of infusion solutions product, reduces residual oxygen and dissolved oxygen in product, and concentration of metal ions in solution, is the effective method that guarantees Amino Acid Compound Injection product quality.

Ultimate principle of the present invention is: before Amino Acid Compound Injection (compositions) preparation; in material-compound tank, pass into pure nitrogen gas to drain the dissolved oxygen in water; whole process using 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, regulator solution pH value is in 5.5～7.0 scopes on the one hand, 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 unstable aminoacid on group effect and produce stabilizer function.In addition, the antioxidation that cysteine hydrochloride self has, can further guarantee the stability of product.

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

1, whole process using 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 the nitrogen mode of the filling better effects if of routine, more can reduce the residual oxygen in product.

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

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

The specific embodiment

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, 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 ℃), pass into pure nitrogen gas, open and stir, for subsequent use; Following all operations were all carries out under nitrogen protection.

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

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

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

E, stir after, be cooled to 40 or 41 or 42 or 43 or 44 or 45 ℃, add successively cysteine hydrochloride, tryptophan, malic acid, 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, through the de-charcoal of titanium rod filter circulating filtration, pump in dilute preparing tank and add to the full amount of water for injection, and 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, jump a queue, roll lid, 115 or 117 or 121 ℃ 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, 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

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, and commercially available Amino Acid Compound Injection (15-HBC) (adds 0.02%(w/v) as a control group sodium pyrosulfite, with glacial acetic acid regulator solution pH value to 6.0 left and right).

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, by product respectively at placing 10 days under illumination 4500lx ± 500lx, 60 ℃ of conditions of high temperature, detect respectively at sampling in the 0th, 5,10 days, 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.

Result is investigated in table 1 Amino Acid Compound Injection (15-HBC) 4500lx ± 500lx contrast

Result is investigated in 60 ℃ of contrasts of table 2 Amino Acid Compound Injection (15-HBC)

Can find out 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) are investigated 10 days respectively under 4500lx ± 500lx and 60 ℃ of conditions, from the variation tendency of the aspects such as light transmittance, methionine, tryptophan and arginine content, the present composition is obviously stable than commercially available product, character, pH value and other amino acid contents of solution 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 of sample (anaphylaxis, blood vessel irritation and hemolytic):

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 specific safety test local, that whole body administration is relevant.0.9% sodium chloride injection is as negative control product, and 20% human albumin is as positive reference substance.

Test method and result:

1, vascular stimulation tests

1.1 test method

Get 3 of adult healthy white rabbit, test sample group is from the slow intravenous injection 10mL/kg of left ear edge test sample stock solution, and auris dextra edge constant speed identical size injection is penetrated sodium chloride injection.Be administered once every day, continuous 5 days.During administration, perusal administration every day local vascular has or not thrombosis, and surrounding tissue has or not the inflammatory reactions such as red and swollen blood stasis.After 48 hours, put to death animal in last administration, get rapidly its ear tissue (from entry point centripetal direction 2～3cm), 10% formalin is fixed, paraffin embedding, and conventional film-making, HE dyeing, light Microscopic observation blood vessel and tissue morphology change.

1.2 result of the test

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

Table 3 vascular stimulation tests perusal result

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

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

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

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

2, hypersensitive test

2.1 test method

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

2.2 result of the test

After test sample group and negative control treated animal intravenously administrable, 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: under above-mentioned experimental condition, systemic anaphylaxis does not appear 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, add successively 2% erythrocyte suspension and normal saline by table 7 proportional quantity, after mixing, place half an hour in 37 ± 0.5 ℃ of calorstats, then manage the test sample stock solution that adds respectively different volumes 1～No. 5, manage negative control tube No. 6 and add normal saline, manage positive contrast No. 7 and add water for injection, after shaking up, put in 37 ± 0.5 ℃ of calorstats.Start to observe once every 15min, after 1 hour, observed once every 1 hour, Continuous Observation 3 hours, as solution is transparent redness, 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 ℃ of insulation 15min, there is haemolysis in solution, and add 1～No. 5 pipe of need testing solution, commercially available control drug solution to manage for 8～No. 12, No. 6 sodium chloride injection pipe solution is not all 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 numbering

No. 1 pipe

No. 2 pipes

No. 3 pipes

No. 4 pipes

No. 5 pipes

No. 6 pipes

No. 7 pipes

37 ℃ of insulation 15min

-

+++

37 ℃ of insulation 30min

-

+++

37 ℃ of insulation 45min

-

+++

37 ℃ of insulation 1h

-

+++

37 ℃ of insulation 2h

-

+++

37 ℃ of insulation 3h

-

+++

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

By zest, haemolysis and allergy etc. and specific safety test local, that whole body administration is relevant, result show to adopt Amino Acid Compound Injection (15-HBC) that this prescription and preparation method produce to rabbit vein blood vessel without obvious irritation, rabbit erythrocyte is not caused to haemolysis and agglutination, be there is not to anaphylaxis in Cavia porcellus, clinical use safety.

Three, the study on the stability of sample:

For present composition steady quality is described, by the Amino Acid Compound Injection of preparing according to embodiment 1 (15-HBC) compositions, under room temperature condition, place, 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 the Amino Acid Compound Injection of preparing according to embodiment 2 (15-HBC) compositions, under 40 ℃ of conditions, place, 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) the room temperature investigation result that keeps sample

40 ℃ of investigation results that keep sample of table 10 Amino Acid Compound Injection (15-HBC)

As can be seen from Table 9, Amino Acid Compound Injection of the present invention (15-HBC) compositions is deposited after 24 months at ambient temperature, and the indexs such as character, pH value, light transmittance and amino acid content are without significant change.As can be seen from Table 10, Amino Acid Compound Injection of the present invention (15-HBC) compositions is deposited after 6 months under 40 ℃ of conditions, and 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 modifications or supplement or adopt similar mode to substitute described specific embodiment, but can't depart from spirit of the present invention or surmount the defined scope of appended claims.

Claims

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

Raw material content of starting materials consumption

Isoleucine 6.66-8.5g, leucine 12.78-15g,

Lysine acetate 4.8-7g, methionine 1.5-3.5g,

Phenylalanine 2.2-4.5g, threonine 1.0-3.5g,

Tryptophan 0.3-1.5g, valine 6.86-10.5g,

Alanine 2-7g, arginine 4.8-7.5g,

Histidine 1-2.5g, proline-4 .3-8.5g,

Serine 2.3-4.5g, glycine 2.3-4.5g,

Cysteine hydrochloride 0.1-0.4g, malic acid 0.3g ~ 3.0g,

Water for injection surplus;

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

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

Raw material content of starting materials consumption

Isoleucine 7-8g, leucine 13-14.5g,

Lysine acetate 5-6.5g, methionine 1.8-3.2g,

Phenylalanine 2.5-4.2g, threonine 1.4-3.2g,

Tryptophan 0.8-1.2g, valine 7.5-9g,

Alanine 3-6g, arginine 5-7g,

Histidine 1.2-2.2g, proline-4 .6-8.2g,

Serine 2.6-4.2g, glycine 2.8-4.2g,

Cysteine hydrochloride 0.15-0.35g, malic acid 0.8g ~ 2.5g,

Water for injection surplus;

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

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

Raw material content of starting materials consumption

Isoleucine 7.2-7.66g, leucine 13.5-14g,

Lysine acetate 5.5-6g, methionine 2-3g,

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

Tryptophan 0.9-1.1g, valine 8-8.86g,

Alanine 4-5g, arginine 5.5-6.5g,

Histidine 1.6-2g, proline 5.6-7.5g,

Serine 3-4g, glycine 3-4g,

Cysteine hydrochloride 0.19-0.3g, malic acid 1g ~ 2g,

Water for injection surplus;

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

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

Raw material content of starting materials consumption

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.

5. a preparation method for arbitrary described Amino Acid Compound Injection-HBC compositions in claim 1-4, 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, below the nitrogen protection of process for preparation whole process using;

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

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

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

E, stir after, be cooled to 40～45 ℃, 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, through the de-charcoal of titanium rod filter circulating filtration, pump in dilute preparing tank and add to the full amount of water for injection, and 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%;