CN101933922B - Amino acid composition containing new antioxidant - Google Patents
Amino acid composition containing new antioxidant Download PDFInfo
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- CN101933922B CN101933922B CN 201010275130 CN201010275130A CN101933922B CN 101933922 B CN101933922 B CN 101933922B CN 201010275130 CN201010275130 CN 201010275130 CN 201010275130 A CN201010275130 A CN 201010275130A CN 101933922 B CN101933922 B CN 101933922B
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Abstract
The invention discloses an amino acid composition containing a new antioxidant. The compound amino acid injection (18AA-VII) with different concentrations is characterized by being prepared from 9.10 g of isoleucine, 12.9 g of leucine, 10.00 g of lysine acetate, 4.40 g of methionine, 7.00 g of phenylalanine, 7.5 g of threonine, 1.30 g of tryptophan, 14.00 g of valine, 7.10 g of alanine, 9.00 g of arginine, 1.00 g of aspartic acid, 0.50 g of glutamic acid, 5.00 g of histidine, 5.00 g of proline, 1.70 g of serine, 0.40 g of tyrosine, 7.00 g of glycine 0.35 g of cysteine, 0.20-0.30 g of citric acid and a proper amount of pH regulator. The composition does not contain sulfite antioxidants, the harm of sulfites to human bodies is solved, and thus, the product becomes safer in clinic use. Detection results of accelerated tests show that the stability of the compound amino acid injection is better than or the same to that of like products.
Description
Technical field
The invention belongs to medical technical field, more specifically relate to a kind of amino acid composition that contains new antioxidant and preparation method thereof.
Background technology
Amino Acid Compound Injection (18AA-VII) is to add the formulated sterile water solution of adjuvant by 18 seed amino acids, and is clinical in amino acid supplements, the scalable nitrogen balance, and the promotion protein in body is synthetic and the healing of wound.
Because aminoacid is very unstable in solution, very easily oxidized and produce the harmful material of series of complex.From the sixties in 20th century Amino Acid Compound Injection put into production use, for guaranteeing the stability of product, must add the sulphite compounds with unique antioxidation, such as sodium sulfite, sodium pyrosulfite etc.
Up to the present, in the Amino Acid Compound Injection class medicine of national Bureau of Drugs Supervision approved list marketing, the quality standard of many kinds all contains sulphite, and equal unmatchful sulphite assay projects.Why the content of sulphite is not made stricter control, basic reason is the superior oxidation resistance that this material can not be substituted, and under present technical conditions, also can't produce the Amino Acid Compound Injection that does not contain sulphite.
Yet from the eighties in 20th century, along with the development of clinical pharmacy, pharmacology and medical science, people begin to recognize the toxic and side effects of sulfites material after having carried out comparatively deep research aspect the safety of sulphite.Simultaneously, the pharmaceutical control and administration authorities of western developed country also step up to collect the report of relevant clinical adverse.Modal relevant toxicity is that sulphite is irritated clinically, and symptom is bronchospasm, stridulate, and dyspnea, pernicious laryngeal edema, hypotension, shock, in addition dead.Research to the aspects such as pharmacology, molecular biology, toxicology and drug interaction of sulfites has confirmed that also sulfites is as the reality of infusion products antioxidant and potential danger.
Sulfites has special drug interaction in Amino Acid Compound Injection.The Amino Acid Compound Injection that contains sulphite can cause the degraded of some vitamin, and the speed of degraded has substantial connection with the concentration of sulphite.As add thiamine in the Amino Acid Compound Injection that contains the 500mg/l sodium sulfite, room temperature storage was almost all degraded after 24 hours; VB
1With folic acid be can obvious degradation after 24 hours in the vein total nutrient admixture of 100mg/l at sulfite concentration; When sulphite exists, the content of tryptophan approximately is reduced to 75% of normal value, people suspect that also 6 kinds of catabolites of tryptophan are to human liver's toxic action, because test find to accept to contain the hepatocyte tissue of rat of the Amino Acid Compound Injection injection of sulphite variation has occured, its liver enzyme, bilirubin and portal vein on every side fatty infiltration all have and increase.
The common indication that can observe on human body is blood plasma mesobilirubin and amino transaminase's decline.The impact of sulphite on multiple living matter also found in research.The irreversible reaction of the cystine linkage in sulphite and DNA (deoxyribonucleic acid) (DNA), adenylic acid, vitamin K3, uracil, cytosine and the protein may be the reason of sulphite side reaction, and the cross-linking reaction of chromosome and sulphite also may be the major reason of its side reaction in addition.
To the mid-80, sulfites is familiar with more fully to the toxic and side effects of human body.For this reason, countries in the world are limited its application in medicine and food one after another.Though pharmacopoeia of each country is variant to type and the consumption of additives in the injection, from security consideration, think that the consumption of additives is more few better.Permission daily intaking amount (ADI) such as sulphite in foods is restricted to approximately 0.7mgSO in western countries
2/ kg body weight, the people who is equivalent to 70 kg body weight takes in 80 milligrams of sodium sulfitees.
National drug standards WS1-(X-005)-2006Z regulation contains sodium sulfite 300mg in every liter of Amino Acid Compound Injection (18AA-VII), and international standard is also basic identical.
Standard Central Asia sulphates content is higher than the permission daily intaking amount, and its toxic and side effects is obviously to exist; Even sulphite content is lower than the permission daily intaking amount, can not get rid of sulphite to the potential hazard of human body, therefore the preparation that does not contain sulphite of the thorough elimination of development sulphite toxic and side effects is very necessary.
Up to the present, the Amino Acid Compound Injection (18AA-VII) that domestic enterprise produces all contains sulphite; Also have no the relevant Chinese patent application that does not contain the Amino Acid Compound Injection (18AA-VII) of sulphite.
Chinese patent CN1189167C discloses a kind of Amino Acid Compound Injection, it is characterized in that: the pyrosulfurous acid salt content as antioxidant in this injection is 10-30mg/L.
Chinese patent CN101120917A and CN101120918A disclose the Amino Acid Compound Injection that does not contain antioxidant, it is characterized in that the overall process nitrogen protection of producing.
As long as the oxygen in the system is thoroughly removed, just can not add antioxidant sulphite in theory, be practically limited to technical conditions and oxygen content can only be reduced to low-down level.See from its disclosed technique also to have leak, can achieve the goal also exists uncertain factor.It is worthy of note; the manufacturing enterprise of the present most Amino Acid Compound Injections of China does not also possess process conditions and the equipment of production overall process nitrogen protection; reach such requirement; that need to remould oneself thoroughly puts into the melting pot; not only drop into huge; and can achieve the goal and also have uncertain factor, can say that fully oxygen-free in the solution is impossible realize in actual production.
Therefore explore and produce the Amino Acid Compound Injection that does not contain the sulfites antioxidant, be worth research.
Summary of the invention
The object of the invention is to develop a kind of amino acid composition that contains new antioxidant.
Another object of the present invention is to provide preparation a kind of preparation method that contains the amino acid composition of new antioxidant.
In this Amino Acid Compound Injection, the content of sulfites is 0, therefore can thoroughly eliminate the toxic and side effects of sulfites to human body.
According to technical scheme of the present invention, a kind of amino acid composition that contains new antioxidant is the Amino Acid Compound Injection (18AA-VII) of being made variable concentrations by 18 seed amino acids and/or its salt and adjuvant in following parts by weight ratio:
Isoleucine 8.19-10.01g leucine 11.61-14.19g
Lysine acetate 9.00-11.00g methionine 3.96-4.84g
Phenylalanine 6.30-7.70g threonine 6.75-8.25g
Tryptophan 1.17-1.43g valine 12.60-15.40g
Alanine 6.39-7.81g arginine 8.10-9.90g
Aspartic Acid 0.90-1.10g glutamic acid 0.45-0.55g
Histidine 4.50-5.50g proline-4 .50-5.50g
Serine 1.53-1.87g tyrosine 0.36-0.44g
Glycine 6.30-7.70g cysteine 0.30-0.40g
Citric acid 0.10-1.00g water for injection is an amount of
The pH value regulator is an amount of
Total amount is 1000ml;
The pH value of described compositions is 6.8-7.8;
Described pH value regulator is hydrochloric acid solution, acetum, NaOH solution, Na
2CO
3A kind of in the solution or two kinds, concentration is 0.1mol/L;
According to technical scheme of the present invention, a kind of prescription parts by weight ratio that contains the amino acid composition of new antioxidant is:
Isoleucine 9.10g leucine 12.90g
Lysine acetate 10.00g methionine 4.40g
Phenylalanine 7.00g threonine 7.50g
Tryptophan 1.30g valine 14.00g
Alanine 7.10g arginine 9.00g
Aspartic Acid 1.00g glutamic acid 0.50g
Histidine 5.00g proline 5.00g
Serine 1.70g tyrosine 0.40g
Glycine 7.00g cysteine 0.35g
Citric acid 0.10-0.50g water for injection is an amount of
The pH value regulator is an amount of
Total amount is 1000ml;
The pH value of described compositions is 6.8-7.8;
Described pH value regulator is hydrochloric acid solution, acetum, NaOH solution, Na
2CO
3A kind of in the solution or two kinds, concentration is 0.1mol/L;
According to technical scheme of the present invention, a kind of preparation method that contains the amino acid composition of new antioxidant is characterized in that may further comprise the steps:
(1) takes by weighing each former, adjuvant by prescription;
(2) get the water for injection of full dose about 80%, be heated to more than 95 ℃, more than the logical nitrogen 30min of insulation, 80-85 ℃ of control water temperature is in the lower citric acid that adds of nitrogen current protection, dissolving;
(3) under the nitrogen current protection, add again Aspartic Acid, tyrosine, leucine, phenylalanine, glutamic acid, isoleucine, valine, methionine, histidine, alanine, threonine, serine, proline, glycine, arginine and lysine acetate, be stirred to dissolving;
(4) under the nitrogen current protection, medicinal liquid is cooled to about 50 ℃, continue to add tryptophan and cysteine, stirring and dissolving is regulated pH6.8 to 7.8, injects the water standardize solution to ormal weight, uniform stirring, add active carbon 0.5g by every 1000ml solution, then insulation absorption 15min returns more than the filter 15min;
(5) under nitrogen current protection, with coarse filtration liquid through 0.45um, the continuous fine straining of 0.22um micropore filter element;
(6) in nitrogen current protection is lower fine straining liquid is filled in the glass infusion bottle, every bottle of 100ml or 200ml, top plug rolls lid, in 115 ℃ of sterilization 30min, lamp inspection, and get final product.
(7) in nitrogen current protection is lower fine straining liquid is filled in the non-PVC multi-layer co-extruded transfusion bag, every bag of 100ml or 200ml, sealing, 115 ℃ of sterilization 30min, lamp inspection is put into oxygen-inhibiting agent again and is put outer bag, after the sealing, and get final product.
Carry out finding in a kind of amino acid composition research that contains new antioxidant at us, as long as the aminoacid that is in solution state with the oxygen of denier once contact, just can inspire amino acid whose oxidative decomposition, after this this chemical reaction just can go on automatically, might not need the continuous participation of extraneous oxygen, metal ion has catalytic action in this process.Therefore, although product solution is sealed in the infusion bottle, extraneous oxygen can't enter, and product can constantly decompose, until rotten can't the use.As long as the oxygen in the system is thoroughly removed, just can not add antioxidant sulfurous acids salt in theory, be practically limited to technical conditions and oxygen content can only be reduced to low-down level, can not solve amino acid whose oxidative decomposition problem fully.
Therefore will solve amino acid whose oxidative decomposition just need to be from two aspects: the one, and the aminoacid that reduces as far as possible solution state contacts with the oxygen of denier; The 2nd, the catalysis problem of solution trace metal ion.These two links solve well, just can cut off the generation of amino acid whose oxidative decomposition.
The ultimate principle of technical solution of the present invention is: by heating water for injection, drive away the micro amount of oxygen that is dissolved in the water; Under nitrogen protection, can suppress preferably dissolving in again of extraneous oxygen; Because the citric acid that adds has preferably chelating ability, suppress the catalytic action of trace metal ion in the solution simultaneously, solved preferably amino acid whose oxidized problem; In addition because the antioxidation that the cysteine in the compositions has has been cut off the oxygen contact of aminoacid with denier, with collaborative the stable of Amino Acid Compound Injection that keep of citric acid.
The invention has the advantages that:
1. by the method for heating, solved micro amount of oxygen problem soluble in water;
2. by omnidistance inflated with nitrogen protection, solved the oxygen in the technical process and dissolved in again problem;
3. by the chelation of citric acid, solved the problem that may be brought into the trace metal ion in the solution in the production process, we find that citric acid has good potentiation to the antioxidation of cysteine simultaneously;
4. the antioxidation that has by cysteine has been cut off the oxygen contact of aminoacid with denier;
5. owing to containing cysteine in the prescription, so do not need other increase.
Comprehensive function by above-mentioned advantage, stopped the technique leak that Amino Acid Compound Injection (18AA-VII) may exist in producing, therefore the product that the present invention produces does not contain the sulphite kind antioxidant fully, thoroughly solved the harm of sulfites to human body, made products obtained therefrom safer.The transformation that can greatly save simultaneously Amino Acid Compound Injection manufacturing enterprise drops into, and is fit to large-scale industrial production.
Below by related tests technical scheme of the present invention is described further:
One, the test of antioxidant Citric Acid Dosage
By prescription of the present invention and preparation technology, the different sample of preparation Amino Acid Compound Injection (18AA-VII) owing to containing cysteine in the prescription, need not to add cysteine hydrochloride again in the antioxidant, and Citric Acid Dosage sees Table 1 in the sample:
Antioxidant citric acid and cysteine hydrochloride consumption in table 1 sample
| Test group | ck | 1 | 2 | 3 | 4 | 5 |
| Citric acid (g/L) | 0 | 0.1 | 0.2 | 0.3 | 0.4 | 0.5 |
Blank: do not contain citric acid; Test 30 bottles every group, the sample of testing is placed 60 ℃ of calorstats, maintain the circulation of air, took a sample to check in the 0th, 5,10 day its character, light transmittance, pH value etc. are judged test effect with the 10th day check result, the results are shown in Table 2.
Table 2: the test situation table of Citric Acid Dosage
Result of the test shows: the product that does not contain citric acid is unstable at storage period.Citric Acid Dosage increases, and non-oxidizability improves, and when Citric Acid Dosage surpasses 0.3g/L, non-oxidizability improves not obvious; We think: citric acid is oxidized at inhibition aminoacid, and good effect has been brought into play in the stabilization formulations aspect, simultaneously the non-oxidizability of cysteine is had potentiation.Satisfying under the prerequisite of preparation stability, use less additives as far as possible, owing to containing cysteine in the preparation, therefore just do not need other interpolation.The results showed that the consumption of citric acid is that 0.1-0.5g/L has better antioxidant effect, the consumption of optimization citric acid is 0.2-0.3g/L.
Two. sample and the commercially available stable comparative test that contains the like product of sodium pyrosulfite
By prescription of the present invention and preparation technology, the different sample of preparation Amino Acid Compound Injection (18AA-VII):
Test group 1: contain citric acid 0.2g/L;
Test group 2: with reference to Chinese patent CN1189167C method, use the sodium pyrosulfite of minimum flow, contain sodium pyrosulfite 0.01g/L;
Test group 3: contain sodium sulfite 0.3g/L with reference to national drug standards WS1-(X-005)-2006Z regulation, identical with the contained sodium sulfite amount in present commercial like product.
For investigating the stability of prepared sample, we adopt accelerated test method, and the sample of testing is placed 60 ℃ of calorstats, improve its oxidation rate.If can keep stable under acceleration environment, the stability under 5-25 ℃ and shading condition will be better so.Produce 40 bottles for every group, get 10 bottles for every batch, put into respectively and place 60 ℃ of calorstats placements 5 days, 10 days, 30 days, maintain the circulation of air.
By the national drug standards WS1-of State Food and Drug Administration (X-005)-2006Z, the appearance character of test sample, light transmittance and pH value the results are shown in Table 3, table 4, table 5, table 6.
1, sample detected its character, light transmittance, pH value etc. in the time of 0 day, the results are shown in Table 3.
Table 3: sample is testing result in the time of 0 day
2, sample took out on the 5th day, checked its character, light transmittance, pH value etc., the results are shown in Table 4.
Table 4: sample was the 5th day testing result
With 0 day result relatively, but the logical oxidized degree of light rate response sample, logical light rate score is higher, the oxidized degree of interpret sample is less, the stability of sample is better.The result shows: 3 groups of test specimens the 5th day character, light transmittance, pH value there are no significant difference.
3, sample took out on the 10th day, checked its character, light transmittance, pH value etc., the results are shown in Table 5.
Table 5: sample was the 10th day testing result
Result of the test showed: with 0 day and result's comparison in 5 days, 3 groups of test specimens the 10th day character, light transmittance, pH value show subtle difference, experimental group 1,2,3 products obtained therefrom quality are all qualified through accelerated test, but experimental group 2 products obtained therefrom character are little yellow.
4, sample took out on the 30th day, checked its character, light transmittance, pH value etc., the results are shown in Table 6.
Table 6: sample was the 30th day testing result
Result of the test showed: with 0 day, 5 days, 10 days results relatively, 3 groups of test specimens the 30th day character, light transmittance, pH value have shown larger difference, experimental group 1,3 products obtained therefrom quality are all qualified through accelerated test, but experimental group 1 is better than the stability of experimental group 3, and experimental group 2 products obtained therefrom quality are defective through accelerated test.
Can find out character, light transmittance, the pH value of the sample that contains citric acid from experimental result, have the effect slightly excellent with the preparation that contains sodium sulfite 300mg/L, can replace the sodium sulfite that can cause serious toxic and side effects fully, its non-oxidizability meets the requirement of similar drug national standard fully.
Three, sample quality detects
Be to investigate the quality of product of the present invention, after we make respectively at product 0 month, January, February, in March, in June, test by the standard of the national drug standards WS1-of State Food and Drug Administration (X-005)-2006Z " Amino Acid Compound Injection (18AA-VII) ".
Testing result shows: the indices of Amino Acid Compound Injection (18AA-VII) sample that contains citric acid 0.2g/L is qualified, and product is qualified.Concrete testing result sees Table 7.
Table 7: Amino Acid Compound Injection of the present invention (18AA-VII) quality testing result
From above-mentioned testing result, each index of sample shows that without significant change sample quality is stable.Having good stability of product of the present invention, it is feasible also having reacted technical scheme of the present invention, effectively.
Below by embodiment technical solution of the present invention is described further, but technical solution of the present invention is not limited to embodiment.
Embodiment 1:
1, prescription:
Isoleucine 9.10g leucine 12.90g lysine acetate 10.00g
Methionine 4.40g phenylalanine 7.00g threonine 7.50g
Tryptophan 1.30g valine 14.00g alanine 7.10g
Arginine 9.00g Aspartic Acid 1.00g glutamic acid 0.50g
Histidine 5.00g proline 5.00g serine 1.70g
Tyrosine 0.40g glycine 7.00g cysteine 0.35g
Citric acid 0.1g water for injection is an amount of
Full dose 1000ml
2, preparation technology
(1) takes by weighing each former, adjuvant by prescription;
(2) get the water for injection of full dose about 80%, be heated to more than 95 ℃, more than the logical nitrogen 30min of insulation, 80-85 ℃ of control water temperature is in the lower citric acid that adds of nitrogen current protection, dissolving;
(3) under the nitrogen current protection, add again Aspartic Acid, tyrosine, leucine, phenylalanine, glutamic acid, isoleucine, valine, methionine, histidine, alanine, threonine, serine, proline, glycine, arginine and lysine acetate, be stirred to dissolving;
(4) under the nitrogen current protection, medicinal liquid is cooled to about 50 ℃, continue to add tryptophan and cysteine, stirring and dissolving, regulating pH with 0.1mol/L acetum and 0.1mol/L sodium carbonate liquor is 7.0 to 7.5, injects the water standardize solution to ormal weight, uniform stirring, add active carbon 0.5g by every 1000ml solution, then insulation absorption 15min returns more than the filter 15min;
(5) under nitrogen current protection, with coarse filtration liquid through 0.45 μ m, the continuous fine straining of 0.22 μ m micropore filter element;
(6) in the nitrogen current protection is lower fine straining liquid is filled in the glass infusion bottle, every bottle of 200ml, top plug roll lid, in 115 ℃ of sterilization 30min, and lamp inspection, and get final product.
Embodiment 2:
1, prescription:
Isoleucine 8.19g leucine 11.61g lysine acetate 9.00g
Methionine 3.96g phenylalanine 6.30g threonine 6.75g
Tryptophan 1.17g valine 12.60g alanine 6.39g
Arginine 8.10g Aspartic Acid 0.90g glutamic acid 0.45g
Histidine 4.50g proline-4 .50g serine 1.53g
Tyrosine 0.36g glycine 6.30g cysteine 0.32g
Citric acid 0.2g water for injection is an amount of
Full dose 1000ml.
2, preparation technology
(1) takes by weighing each former, adjuvant by prescription;
(2) get the water for injection of full dose about 80%, be heated to more than 95 ℃, more than the logical nitrogen 30min of insulation, 80-85 ℃ of control water temperature is in the lower citric acid that adds of nitrogen current protection, dissolving;
(3) under the nitrogen current protection, add again Aspartic Acid, tyrosine, leucine, phenylalanine, glutamic acid, isoleucine, valine, methionine, histidine, alanine, threonine, serine, proline, glycine, arginine and lysine acetate, be stirred to dissolving;
(4) under the nitrogen current protection, medicinal liquid is cooled to about 50 ℃, continue to add tryptophan and cysteine stirring and dissolving, regulating pH with 0.1mol/L acetum, 0.1mol/L sodium hydroxide solution is 7.2 to 7.6, inject the water standardize solution to ormal weight, uniform stirring adds active carbon 0.5g by every 1000ml solution, then insulation absorption 15min returns more than the filter 15min;
(5) under nitrogen current protection, with coarse filtration liquid through 0.45 μ m, the continuous fine straining of 0.22 μ m micropore filter element;
(6) in nitrogen current protection is lower fine straining liquid is filled in the non-PVC multi-layer co-extruded transfusion bag, every bag of 100ml, sealing, in 115 ℃ of sterilization 30min, lamp inspection is put into oxygen-inhibiting agent again and is put outer bag, after the sealing and get final product.
Embodiment 3:
1, prescription:
Isoleucine 91.0g leucine 129.0g lysine acetate 100.0g
Methionine 44.0g phenylalanine 70.0g threonine 75.0g
Tryptophan 13.0g valine 140.0g alanine 71.0g
Arginine 90.0g Aspartic Acid 10.0g glutamic acid 5.0g
Histidine 50.0g proline 50.0g serine 17.0g
Trorsine 14 .0g glycine 70.0g cysteine 3.5g
Citric acid 2.0g water for injection is an amount of
Full dose 10000ml
2, preparation technology
(1) takes by weighing each former, adjuvant by prescription;
(2) water for injection of adding 80% in blend tank, heating was filled nitrogen 30 minutes, and temperature remains on more than 85 ℃, adds citric acid under the inflated with nitrogen protection, stirs dissolving;
(3) under the nitrogen current protection, add again Aspartic Acid, tyrosine, leucine, phenylalanine, glutamic acid, isoleucine, valine, methionine, histidine, alanine, threonine, serine, proline, glycine, arginine and lysine acetate, be stirred to dissolving;
(4) under the nitrogen current protection, medicinal liquid is cooled to about 50 ℃, continue to add tryptophan and cysteine stirring and dissolving, regulating pH with 0.1mol/L acetum, 0.1mol/L sodium hydroxide solution is 6.8 to 7.3, inject the water standardize solution to ormal weight, uniform stirring adds active carbon 0.5g by every 1000ml solution, then insulation absorption 15min returns more than the filter 15min;
(5) under nitrogen current protection, with coarse filtration liquid through 0.45 μ m, the continuous fine straining of 0.22 μ m micropore filter element;
(6) in nitrogen current protection is lower fine straining liquid is filled in the non-PVC multi-layer co-extruded transfusion bag, every bag of 200ml, sealing, in 115 ℃ of sterilization 30min, lamp inspection is put into oxygen-inhibiting agent again and is put outer bag, after the sealing and get final product.
Embodiment 4:
1, prescription:
Isoleucine 100.1g leucine 141.9g lysine acetate 110.0g
Methionine 48.4g phenylalanine 77.0g threonine 82.5g
Tryptophan 14.3g valine 154.0g alanine 78.1g
Arginine 99.0g Aspartic Acid 11.0g glutamic acid 5.5g
Histidine 55.0g proline 55.0g serine 18.7g
Trorsine 14 .4g glycine 77.0g cysteine 3.8g
Citric acid 3.0g water for injection is an amount of
Full dose 10000ml
2, preparation technology
(1) takes by weighing each former, adjuvant by prescription;
(2) water for injection of adding 80% in blend tank, heating was filled nitrogen 30 minutes, and temperature remains on more than 85 ℃, adds citric acid under the inflated with nitrogen protection, stirs dissolving;
(3) under the nitrogen current protection, add again Aspartic Acid, tyrosine, leucine, phenylalanine, glutamic acid, isoleucine, valine, methionine, histidine, alanine, threonine, serine, proline, glycine, arginine and lysine acetate, be stirred to dissolving;
(4) under the nitrogen current protection, medicinal liquid is cooled to about 50 ℃, continue to add tryptophan and cysteine stirring and dissolving, regulating pH with 0.1mol/L acetum, 0.1mol/L sodium hydroxide solution is 7.0 to 7.5, inject the water standardize solution to ormal weight, uniform stirring adds active carbon 0.5g by every 1000ml solution, then insulation absorption 15min returns more than the filter 15min;
(5) under nitrogen current protection, with coarse filtration liquid through 0.45 μ m, the continuous fine straining of 0.22 μ m micropore filter element;
(6) in the nitrogen current protection is lower fine straining liquid is filled in the glass infusion bottle, every bottle of 200ml, top plug roll lid, in 115 ℃ of sterilization 30min, and lamp inspection, and get final product.
Embodiment 5:
1, prescription:
Isoleucine 91.0g leucine 129.0g lysine acetate 100.0g
Methionine 44.0g phenylalanine 70.0g threonine 75.0g
Tryptophan 13.0g valine 140.0g alanine 71.0g
Arginine 90.0g Aspartic Acid 10.0g glutamic acid 5.0g
Histidine 50.0g proline 50.0g serine 17.0g
Trorsine 14 .0g glycine 70.0g cysteine 3.5g
Citric acid 2.0g water for injection is an amount of
Full dose 10000ml
2, preparation technology
(1) takes by weighing each former, adjuvant by prescription;
(2) water for injection of adding 80% in blend tank, heating was filled nitrogen 30 minutes, and temperature remains on more than 85 ℃, adds citric acid under the inflated with nitrogen protection, stirs dissolving;
(3) under the nitrogen current protection, add again Aspartic Acid, tyrosine, leucine, phenylalanine, glutamic acid, isoleucine, valine, methionine, histidine, alanine, threonine, serine, proline, glycine, arginine and lysine acetate, be stirred to dissolving;
(4) under the nitrogen current protection, medicinal liquid is cooled to about 50 ℃, continue to add tryptophan and cysteine stirring and dissolving, regulating pH with the 0.1mol/L acetum is 6.8 to 7.3, inject the water standardize solution to ormal weight, uniform stirring adds active carbon 0.5g by every 1000ml solution, then insulation absorption 15min returns more than the filter 15min;
(5) under nitrogen current protection, with coarse filtration liquid through 0.45 μ m, the continuous fine straining of 0.22 μ m micropore filter element;
(6) in the nitrogen current protection is lower fine straining liquid is filled in the glass infusion bottle, every bottle of 100ml, top plug roll lid, in 115 ℃ of sterilization 30min, and lamp inspection, and get final product.
Embodiment 6:
1, prescription:
Isoleucine 91.0g leucine 129.0g lysine acetate 100.0g
Methionine 44.0g phenylalanine 70.0g threonine 75.0g
Tryptophan 13.0g valine 140.0g alanine 71.0g
Arginine 90.0g Aspartic Acid 10.0g glutamic acid 5.0g
Histidine 50.0g proline 50.0g serine 17.0g
Trorsine 14 .0g glycine 70.0g cysteine 3.5g
Citric acid 3.0g water for injection is an amount of
Full dose 10000ml
2, preparation technology
(1) takes by weighing each former, adjuvant by prescription;
(2) water for injection of adding 80% in blend tank, heating was filled nitrogen 30 minutes, and temperature remains on more than 85 ℃, adds citric acid under the inflated with nitrogen protection, stirs dissolving;
(3) under the nitrogen current protection, add again Aspartic Acid, tyrosine, leucine, phenylalanine, glutamic acid, isoleucine, valine, methionine, histidine, alanine, threonine, serine, proline, glycine, arginine and lysine acetate, be stirred to dissolving;
(4) under the nitrogen current protection, medicinal liquid is cooled to about 50 ℃, continue to add tryptophan and cysteine stirring and dissolving, regulating pH with the 0.1mol/L acetum is 7.2 to 7.6, inject the water standardize solution to ormal weight, uniform stirring adds active carbon 0.5g by every 1000ml solution, then insulation absorption 15min returns more than the filter 15min;
(5) under nitrogen current protection, with coarse filtration liquid through 0.45 μ m, the continuous fine straining of 0.22 μ m micropore filter element;
(6) in nitrogen current protection is lower fine straining liquid is filled in the non-PVC multi-layer co-extruded transfusion bag, every bag of 200ml, sealing, in 115 ℃ of sterilization 30min, lamp inspection is put into oxygen-inhibiting agent again and is put outer bag, after the sealing and get final product.
Claims (3)
1. amino acid composition that contains antioxidant is characterized in that prescription is:
The pH value regulator is an amount of
Total amount is 1000ml;
The pH value of described compositions is 6.8-7.8;
Described pH value regulator is hydrochloric acid solution, acetum, NaOH solution, Na
2CO
3A kind of in the solution or two kinds, concentration is 0.1mol/l.
2. according to claim 1 a kind of amino acid composition that contains antioxidant, its prescription is:
The pH value regulator is an amount of
Total amount is 1000ml;
The pH value of described compositions is 6.8-7.8.
3. according to claim 1 and 2 a kind of preparation method that contains the amino acid composition of antioxidant is characterized in that may further comprise the steps:
(1) takes by weighing each former, adjuvant by prescription;
(2) get the water for injection of full dose 80%, be heated to more than 95 ℃, more than the logical nitrogen 30min of insulation, 80-85 ℃ of control water temperature is in the lower citric acid that adds of nitrogen current protection, dissolving;
(3) under the nitrogen current protection, add again Aspartic Acid, tyrosine, leucine, phenylalanine, glutamic acid, isoleucine, valine, methionine, histidine, alanine, threonine, serine, proline, glycine, arginine and lysine acetate, be stirred to dissolving;
(4) under the nitrogen current protection, make medicinal liquid be cooled to 50 ℃, continue to add tryptophan and cysteine, stirring and dissolving is regulated pH6.8 to 7.8, injects the water standardize solution to ormal weight, uniform stirring, add active carbon 0.5g by every 1000ml solution, then insulation absorption 15min returns more than the filter 15min;
(5) under nitrogen current protection, with coarse filtration liquid through 0.45 μ m, the continuous fine straining of 0.22 μ m micropore filter element;
(6) in nitrogen current protection is lower fine straining liquid is filled in the glass infusion bottle, every bottle of 100ml or 200ml, top plug rolls lid, in 115 ℃ of sterilization 30min, lamp inspection, and get final product; Or in nitrogen current protection is lower fine straining liquid is filled in the non-PVC multi-layer co-extruded transfusion bag, every bag of 100ml or 200ml, sealing, 115 ℃ of sterilization 30min, lamp inspection is put into oxygen-inhibiting agent again and is put outer bag, after the sealing, and get final product.
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| CN 201010275130 CN101933922B (en) | 2010-09-08 | 2010-09-08 | Amino acid composition containing new antioxidant |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010275130 CN101933922B (en) | 2010-09-08 | 2010-09-08 | Amino acid composition containing new antioxidant |
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| CN101933922B true CN101933922B (en) | 2013-01-30 |
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| CN103006643B (en) * | 2011-09-28 | 2014-01-22 | 辽宁海思科制药有限公司 | Compound injection containing 18 amino acids and preparation method thereof |
| CN102631663B (en) * | 2012-05-02 | 2014-08-20 | 张风帆 | Compound amino acid composition and preparation for treatment of male sterility, impotence and premature ejaculation |
| CN102940628A (en) * | 2012-10-10 | 2013-02-27 | 八峰药化宜昌有限责任公司 | Compound amino acid injection and preparation method thereof |
| CN106361749A (en) * | 2016-10-24 | 2017-02-01 | 安徽富邦药业有限公司 | Preparation method of compound amino acid injection 18AA |
| CN109381423B (en) * | 2017-08-09 | 2022-11-25 | 湖北一半天制药有限公司 | Pharmaceutical composition containing 19 amino acids and preparation method thereof |
| CN110075062A (en) * | 2019-05-23 | 2019-08-02 | 广州绿十字制药有限公司 | A kind of nephrosis amino acid injection |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101439031A (en) * | 2008-12-29 | 2009-05-27 | 郑飞雄 | Pharmaceutical composition containing 18 kinds of amino acid |
| CN101439036A (en) * | 2008-12-22 | 2009-05-27 | 郑飞雄 | Pharmaceutical composition containing 18 kinds of amino acid |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101439036A (en) * | 2008-12-22 | 2009-05-27 | 郑飞雄 | Pharmaceutical composition containing 18 kinds of amino acid |
| CN101439031A (en) * | 2008-12-29 | 2009-05-27 | 郑飞雄 | Pharmaceutical composition containing 18 kinds of amino acid |
Non-Patent Citations (1)
| Title |
|---|
| 国家药典委员会.氨基酸注射液(18AA-Ⅶ).《国家药品标准（新药转正标准西药第六十九册）》.2008,X69-135页. * |
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