CN102861011A - Medicine composition of 18 amino acids and preparation - Google Patents
Medicine composition of 18 amino acids and preparation Download PDFInfo
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- CN102861011A CN102861011A CN2012103845424A CN201210384542A CN102861011A CN 102861011 A CN102861011 A CN 102861011A CN 2012103845424 A CN2012103845424 A CN 2012103845424A CN 201210384542 A CN201210384542 A CN 201210384542A CN 102861011 A CN102861011 A CN 102861011A
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Abstract
The invention belongs to the technical field of medicines and particularly relates to a medicine composition of 18 amino acids and a preparation. The medicine composition adopts 1-thiosorbitol or 1-thiosorbitol and maleic acid as the antioxygen and contains no antioxygens like sulfite, and the medicine composition further has the effect of reducing content of pyroglutamic acid. Injection prepared by the medicine composition has excellent quality.
Description
Technical field
The invention belongs to medical technical field, be specifically related to pharmaceutical composition and preparation and the preparation method of 18 seed amino acids.
Background technology
Amino Acid Compound Injection (18AA) is by the formulated sterile water solution of 18 seed amino acids, has the human body protein of promotion Metabolism of Normal, corrects negative nitrogen balance, replenishes protein, the effect of accelerating wound.Be used for that muscle catabolism under the stress state such as large-area burns, wound and severe infections is hyperfunction, the patient's of digestive system function obstacle, nutrition deterioration and immunologic function degression nutritional support, also be used for patients after surgery, improve its nutritional status.Be used for the patient that the aminoacid such as protein Deficiency of Intake, malabsorption can not satisfy the organism metabolism needs.Also be used for improving the nutriture of patients after surgery.
Amino Acid Compound Injection (18AA) contains the easily oxidation aminoacid such as tryptophan, leucine, therefore, needs to add antioxidant in this medicine, and the antioxidant that uses in the now commercially available Amino Acid Compound Injection is sulphite.Development along with clinical pharmacy, pharmacology and medical science, studies show that, the sulfites material has certain toxic and side effects, sulphite can cause the degraded of some vitamin, the irreversible reaction of the cystine linkage in sulphite and DNA (deoxyribonucleic acid), adenylic acid, vitaminK-3, uracil, cytosine and the protein, sulphite and chromosome generation cross-linking reaction.Therefore, countries in the world are limited the application of sulphite in medicine and food one after another, and it is 0.7mgSO that the countries such as the U.S. limit the sulphite daily intaking amount
2/ kg, the people who is equivalent to 70 kilograms body weight takes in the 80mg sodium sulfite.Make the consumption of sodium sulfite be defined as 1.0g/L in China's Amino Acid Compound Injection, and the quantity of Amino Acid Compound Injection is 500-1000mL/ day, so intake is more than safe dose far away, therefore, study the Amino Acid Compound Injection of new antioxidant, significant.
Summary of the invention
For these reasons, the applicant is in research 18AA injection, determine by experimental study: adopt 1-sulfo-sorbitol, perhaps adopt 1-sulfo-sorbitol and maleic acid as antioxidant, do not contain the sulphite kind antioxidant in this pharmaceutical composition, the content effect that pharmaceutical composition of the present invention also has good reduction pyroglutamic acid (contains glutamic acid in the Amino Acid Compound Injection, glutamic acid can change into pyroglutamic acid under the conditions such as high temperature, and pyroglutamic acid is the carcinogen of bringing out cancer).
The objective of the invention is to be provides a kind of pharmaceutical composition that does not contain 18 seed amino acids of sulphite kind antioxidant for clinical.
Purpose of the present invention provides a kind of pharmaceutical compositions sulphite kind antioxidant, better 18 seed amino acids of safety that do not contain for clinical.
The objective of the invention is provides a kind of and can suppress the pharmaceutical composition that glutamic acid rotating changes into 18 seed amino acids of impurity pyroglutamic acid for clinical.
The present invention is achieved through the following technical solutions.
A kind of pharmaceutical composition of amino acid, wherein proline C
5H
9NO
20.90-1.10 weight portion, serine C
3H
7NO
30.90-1.10 weight portion, alanine C
3H
7NO
21.90-2.10 weight portion, isoleucine C
6H
13NO
23.40-3.60 weight portion, leucine C
6H
13NO
24.80-5.00 weight portion, Aspartic Acid C
4H
7NO
42.40-2.60 weight portion, tyrosine C
9H
11NO
30.20-0.30 weight portion, glutamic acid C
5H
9NO
40.70-0.80 weight portion, phenylalanine C
9H
11NO
25.20-5.40 weight portion, arginine hydrochloride C
6H
14N
4O
2HCL 4.90-5.10 weight portion, lysine hydrochloride C
6H
14N
2O
2HCL 4.20-4.40 weight portion, valine C
5H
11NO
23.50-3.70 weight portion, threonine C
4H
9NO
32.40-2.60 weight portion, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 2.40-2.60 weight portion, tryptophan C
11H
12N
2O
20.80-1.00 weight portion, methionine C
15H
11NO
2S 2.20-2.30 weight portion, cystine C
6H
12N
2O
4S
20.10 weight portion, glycine C
2H
5NO
27.50-7.70 weight portion, pharmaceutic adjuvant 0.04-0.07 weight portion.
The pharmaceutical composition of a kind of amino acid described above, wherein proline C
5H
9NO
21.00 weight portion, serine C
3H
7NO
31.00 weight portion, alanine C
3H
7NO
22.00 weight portion, isoleucine C
6H
13NO
23.52 weight portion, leucine C
6H
13NO
24.90 weight portion, Aspartic Acid C
4H
7NO
42.50 weight portion, tyrosine C
9H
11NO
30.25 weight portion, glutamic acid C
5H
9NO
40.75 weight portion, phenylalanine C
9H
11NO
25.33 weight portion, arginine hydrochloride C
6H
14N
4O
2HCL 5.00 weight portions, lysine hydrochloride C
6H
14N
2O
2HCL 4.30 weight portions, valine C
5H
11NO
23.60 weight portion, threonine C
4H
9NO
32.50 weight portion, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 2.50 weight portions, tryptophan C
11H
12N
2O
20.90 weight portion, methionine C
15H
11NO
2S 2.25 weight portions, cystine C
6H
12N
2O
4S
20.10 weight portion, glycine C
2H
5NO
27.60 weight portion, pharmaceutic adjuvant 0.055 weight portion.
The pharmaceutical composition of amino acid described above, wherein medicinal adjuvant is 1-sulfo-sorbitol in the pharmaceutical composition, or 1-sulfo-sorbitol and maleic acid.
The pharmaceutical composition of amino acid described above is prepared into ejection preparation.Its preparation method can be prepared according to prior art, is 201010513639.1 or following preparation method preparation such as number of patent application:
Get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride, when treating that medicinal liquid is cooled to 50 ℃, add tryptophan; when treating that medicinal liquid is cooled to 45 ℃; add cystine, add until completely dissolved the antioxidant of recipe quantity to fully dissolving, inject water to ormal weight; uniform stirring; 0.45 μ m filter element; 0.22 μ m filter element filtering is filled to filtrate in the non-PVC composite co-extruding film transfusion bag under nitrogen protection, sealing; sterilized 30 minutes, and get final product for 115 ℃.
The application of the pharmaceutical composition of amino acid described above in the medicine of the hypoproteinemia that serious amino acid starvation disease that preparation treatment operation, severe trauma, large-area burns cause and various diseases cause.
The pharmaceutical composition of a kind of amino acid described above, wherein the weight ratio of 1-sulfo-sorbitol and lemon maleic acid is 1: 0.5-0.8.
The pharmaceutical composition of a kind of amino acid described above, wherein the weight ratio of 1-sulfo-sorbitol and maleic acid is 1: 0.60.
The pharmaceutical composition of a kind of amino acid described above, wherein the weight ratio of 1-sulfo-sorbitol and maleic acid is 1: 0.70.
1-sulfo-sorbitol described above refers to sulfo-sorbitol or single sulfo-sorbitol (chief editor such as " Chinese pharmaceutic adjuvant " Luo Mingsheng, Chemical Industry Press, in April, 2006,143 pages)
Following test is on the test of many times basis, carries out the concluding test according to technical solutions according to the invention.
One, antioxidant screening test
Prescription: proline C
5H
9NO
210.0
g, serine C
3H
7NO
310.0g, alanine C
3H
7NO
220.0g, isoleucine C
6H
13NO
235.2g, leucine C
6H
13NO
249.0g, Aspartic Acid C
4H
7NO
425.0g, tyrosine C
9H
11NO
32.5g, glutamic acid C
5H
9NO
47.5g, phenylalanine C
9H
11NO
253.3g, arginine hydrochloride C
6H
14N
4O
2HCL 50.0g, lysine hydrochloride C
6H
14N
2O
2HCL 43.0g, valine C
5H
11NO
236.0, threonine C
4H
9NO
325.0g, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 25.0g, tryptophan C
11H
12N
2O
29.0g, methionine C
15H
11NO
2S 22.5g, cystine C
6H
12N
2O
4S
21.0g, glycine C
2H
5NO
276.0g, antioxidant.
Test 1 group: antioxidant citric acid 2.0g.
Test 2 groups: antioxidant EDTA0.2g.
Test 3 groups: antioxidant cysteine hydrochloride 2.0g.
Test 4 groups: antioxidant citric acid 0.2g, cysteine hydrochloride 2.0g
Test 5 groups: antioxidant Catergen .5g.
Test 6 groups: antioxidant fumaric acid 2.5g.
Test 7 groups: antioxidant EDTA0.2g,, cysteine hydrochloride 2.0g.
Test 8 groups: antioxidant 1-sulfo-sorbitol 0.55g.
Preparation method: get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride; when treating that medicinal liquid is cooled to 50 ℃; add tryptophan; when treating that medicinal liquid is cooled to 45 ℃, add cystine, add until completely dissolved the antioxidant of recipe quantity to fully dissolving; inject water to 10000ml; uniform stirring, 0.45 μ m filter element; 0.22 μ m filter element filtering is filled to filtrate in the non-PVC composite co-extruding film transfusion bag under nitrogen protection; sealing; sterilized 30 minutes, and namely got 40 bags, every bag of 250ml for 115 ℃.(40 bags of each test group)
Test method: different tests group preparation group is tested according to following quality standard.
Quality standard: Amino Acid Compound Injection (18AA)
[working out foundation] WS1-XG-002-2011 of State Food and Drug Administration's " national drug standards ".
[character] this product is colourless clear liquid to little Huang.
[inspection]
PH value should be 5.0～7.0 (two appendix VIH of Chinese Pharmacopoeia version in 2010).
Transmittance is got this product, according to ultraviolet visible spectrophotometry (two appendix IVA of Chinese Pharmacopoeia version in 2010), measures light transmittance at the wavelength place of 430nm, must not be lower than 97.0%.
Result of the test: see Table 1.
Table 1 antioxidant the selection result
The test brief summary: above-mentioned test shows, not that any antioxidant can replace sulphite to use as the antioxidant of Amino Acid Compound Injection, studies show that, test 2 groups, test 4 groups, test 6 groups, test 7 groups, 8 groups of antioxidant of test, determine that tentatively the antioxidant that can be used as Amino Acid Compound Injection uses.
With 2 groups of above-mentioned tests, 4 groups of tests, 6 groups of tests, 7 groups of tests, 8 groups of preparations of test respectively sample is placed high humidity (75% ± 5%), high temperature (60 ℃), high light (investigate 5 under 4500 ± 500LX) conditions, 10d, detect appearance character and light transmittance, result of the test sees Table 2, table 3, table 4:
Table 2 high humidity result of the test
Table 3 hot test result
Table semi-finals phototesting result
Test brief summary: by high temperature, high humidity, highlight test, test 2 groups and 4 groups antioxidant of test and do not meet quality standard, test 7 groups of 6 groups, test, test the antioxidant that 8 groups antioxidant can be used as Amino Acid Compound Injection and use.
Two, antioxidant screening test
On the basis of above-mentioned research, the applicant carries out deep research again, on 8 groups of bases of test, carries out deep research, and test method is as follows:
Prescription: proline C
5H
9NO
210.0g, serine C
3H
7NO
310.0g, alanine C
3H
7NO
220.0g, isoleucine C
6H
13NO
235.2g, leucine C
6H
13NO
249.0g, Aspartic Acid C
4H
7NO
425.0g, tyrosine C
9H
11NO
32.5g, glutamic acid C
5H
9NO
47.5g, phenylalanine C
9H
11NO
253.3g, arginine hydrochloride C
6H
14N
4O
2HCL 50.0g, lysine hydrochloride C
6H
14N
2O
2HCL 43.0g, valine C
5H
11NO
236.0, threonine C
4H
9NO
325.0g, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 25.0g, tryptophan C
11H1
2N
2O
29.0g, methionine C
15H
11NO
2S 22.5g, cystine C
6H
12N
2O
4S
21.0g, glycine C
2H
5NO
276.0g, antioxidant.
Test 9 groups: antioxidant is 1-sulfo-sorbitol 0.35g, maleic acid 0.20g.
Test 10 groups: antioxidant is 1-sulfo-sorbitol 0.34g, maleic acid 0.21g.
Test 11 groups: antioxidant is 1-sulfo-sorbitol 0.33g, maleic acid 0.22g.
Preparation method: get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride; when treating that medicinal liquid is cooled to 50 ℃; add tryptophan; when treating that medicinal liquid is cooled to 45 ℃, add cystine, add until completely dissolved the antioxidant of recipe quantity to fully dissolving; inject water to 10000ml; uniform stirring, 0.45 μ m filter element; 0.22 μ m filter element filtering is filled to filtrate in the non-PVC composite co-extruding film transfusion bag under nitrogen protection; sealing; sterilized 30 minutes, and namely got 40 bags, every bag of 250ml for 115 ℃.(40 bags of each test group)
Test method: different tests group preparation group is tested according to following quality standard.
Quality standard: Amino Acid Compound Injection (18AA)
[working out foundation] WS1-XG-002-2011 of State Food and Drug Administration's " national drug standards ".
[character] this product is colourless clear liquid to little Huang.
[inspection]
PH value should be 5.0～7.0 (two appendix VIH of Chinese Pharmacopoeia version in 2010).
Transmittance is got this product, according to ultraviolet visible spectrophotometry (two appendix IVA of Chinese Pharmacopoeia version in 2010), measures light transmittance at the wavelength place of 430nm, must not be lower than 97.0%.
Result of the test: see Table 5.
Table 5 antioxidant the selection result
With 9 groups of above-mentioned tests, 10 groups of tests, 11 groups of preparations of test respectively sample is placed high humidity (75% ± 5%), high temperature (60 ℃), high light (investigate 5 under 4500 ± 500LX) conditions, 10d, detect appearance character and light transmittance, result of the test sees Table 6, table 7, table 8:
Table 6 high humidity result of the test
Table 7 hot test result
The table phototesting result of the Final 8
Test Summary: test one studies show that with test two, antioxidant fumaric acid, antioxidant 1-sulfo-sorbitol, antioxidant EDTA and cysteine hydrochloride, antioxidant is 1-sulfo-sorbitol and maleic acid, the antioxidant that can be used as in the Amino Acid Compound Injection uses, with the Amino Acid Compound Injection of sulphite as antioxidant, has same quality.
Three, the amino acid pyroglutamic acid detects
Test preparation: test 6 groups to testing 11 groups of preparations in test one and the test two.
Reference substance: pyroglutamic acid, U.S. SIGMA company.
Ion exchange column: internal diameter 1.5cm, high 7cm, filler Dowex 50WX8 is through the 20mL water wash and suspend in water.
Detection method:
Chromatographic condition chromatographic column: Aglient ZORBAX SB-C18 (250mm * 4.6mm, 5 μ m) chromatographic column; Mobile phase: 0.01molL-1 ammonium dibasic phosphate solution (with phosphorus acid for adjusting pH to 1.6); Flow velocity: 1.0mLmin-1; Ultraviolet detection wavelength: 205nm; Column temperature: 15 ℃; Sample size: 50 μ L.
The preparation of reference substance solution: get the about 50mg of pyroglutamic acid reference substance, accurately weighed, put in the 100mL measuring bottle, thin up is to scale, product solution (1) in contrast, precision is measured reference substance solution (1) 5ml, 2ml, 0.5mL respectively, puts in the 10mL measuring bottle, thin up is to scale, in contrast product solution (2), (3), (4).
Assay method: precision is measured above-mentioned 4 kinds of reference substance solution and each 2mL of sample stock solution, adds in the ion exchange column, adds water wash, collects effluent in the 100mL measuring bottle, until effluent is to scale.Precision is measured in the effluent 50 μ L injection liquid chromatographies, and the record chromatogram is pressed peak height by pyroglutamic acid amount in the regression equation calculation sample.
Standard code: pyroglutamic acid content is less than or equal to 7mg/L in the sample.
Result of the test sees Table 9-table 11.
The content detection of the different preparation impurity of the high wet test of table 9
The content detection of the different preparation impurity of table 10 hot test
The content detection of the different preparation impurity of table 11 highlight test
Conclusion (of pressure testing): show by above-mentioned test, antioxidant is that EDTA and cysteine hydrochloride, antioxidant are that the pyroglutamic acid content of the Amino Acid Compound Injection of fumaric acid does not meet prescription, therefore, the applicant determines that antioxidant is 1-sulfo-sorbitol, perhaps 1-sulfo-sorbitol and maleic acid.
Preparation Example
Embodiment 1
A kind of pharmaceutical composition of amino acid, proline C
5H
9NO
29.0g, serine C
3H
7NO
39.0g, alanine C
3H
7NO
219.0g, isoleucine C
6H
13NO
23.40g, leucine C
6H
13NO
248.0g, Aspartic Acid C
4H
7NO
424.0g, tyrosine C
9H
11NO
32.0g, glutamic acid C
5H
9NO
47.0g, phenylalanine C
9H
11NO
252.0g, arginine hydrochloride C
6H
14N
4O
2HCL 49.0g, lysine hydrochloride C
6H
14N
2O
2HCL 42.0g, valine C
5H
11NO
235.0g, threonine C
4H
9NO
324.0g, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 24.0g, tryptophan C
11H
12N
2O
28.0g, methionine C
15H
11NO
2S 22.0g, cystine C
6H
12N
2O
4S
21.0g, glycine C
2H
5NO
275.0g, antioxidant 1-sulfo-sorbitol 0.4g.
Aforementioned pharmaceutical compositions is that supplementary material is prepared into injection; preparation method: get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride; when treating that medicinal liquid is cooled to 50 ℃, add tryptophan, when treating that medicinal liquid is cooled to 45 ℃; add cystine; add until completely dissolved the antioxidant of recipe quantity to fully dissolving, inject water to 10000ml, uniform stirring; 0.45 μ m filter element; 0.22 μ m filter element filtering; under nitrogen protection filtrate is filled in the non-PVC composite co-extruding film transfusion bag, sealing was sterilized 30 minutes for 115 ℃; namely get 40 bags, every bag of 250ml.
Embodiment 2
A kind of pharmaceutical composition of amino acid, wherein proline C
5H
9NO
211.0g, serine C
3H
7NO
311.0g, alanine C
3H
7NO
221.0g, isoleucine C
6H1
3NO
236.0g, leucine C
6H
13NO
250.0g, Aspartic Acid C
4H
7NO
426.0g, tyrosine C
9H
11NO
33.0, glutamic acid C
5H
9NO
48.0g, phenylalanine C
9H
11NO
254.0g, arginine hydrochloride C
6H
14N
4O
2HCL 51.0g, lysine hydrochloride C
6H
14N
2O
2HCL 44.0g, valine C
5H
11NO
237.0g, threonine C
4H
9NO
326.0g, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 26.0g, tryptophan C
11H
12N
2O
210.0g, methionine C
15H
11NO
2S 23.0g, cystine C
6H
12N
2O
4S
21.0g, glycine C
2H
5NO
277.0g, antioxidant 1-sulfo-sorbitol 0.7g.
Aforementioned pharmaceutical compositions is that supplementary material is prepared into injection; preparation method: get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride; when treating that medicinal liquid is cooled to 50 ℃, add tryptophan, when treating that medicinal liquid is cooled to 45 ℃; add cystine; add until completely dissolved the antioxidant of recipe quantity to fully dissolving, inject water to 10000ml, uniform stirring; 0.45 μ m filter element; 0.22 μ m filter element filtering; under nitrogen protection filtrate is filled in the non-PVC composite co-extruding film transfusion bag, sealing was sterilized 30 minutes for 115 ℃; namely get 40 bags, every bag of 250ml.
Embodiment 3
A kind of pharmaceutical composition of amino acid, wherein proline C
5H
9NO
210.0g, serine C
3H
7NO
310.0g, alanine C
3H
7NO
220.0g, isoleucine C
6H
13NO
235.2g, leucine C
6H
13NO
249.0g, Aspartic Acid C
4H
7NO
425.0g, tyrosine C
9H
11NO
32.5g, glutamic acid C
5H
9NO
47.5g, phenylalanine C
9H
11NO
253.3g, arginine hydrochloride C
6H
14N
4O
2HCL 50.0g, lysine hydrochloride C
6H
14N
2O
2HCL 43.0g, valine C
5H
11NO
236.0g, threonine C
4H
9NO
325.0g, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 25.0g, tryptophan C
11H
12N
2O
29.0g, methionine C
15H
11NO
2S 22.5g, cystine C
6H
12N
2O
4S
21.0g, glycine C
2H
5NO
276.0g, antioxidant 1-sulfo-sorbitol 0.55g.
Aforementioned pharmaceutical compositions is that supplementary material is prepared into injection; preparation method: get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride; when treating that medicinal liquid is cooled to 50 ℃, add tryptophan, when treating that medicinal liquid is cooled to 45 ℃; add cystine; add until completely dissolved the antioxidant of recipe quantity to fully dissolving, inject water to 10000ml, uniform stirring; 0.45 μ m filter element; 0.22 μ m filter element filtering; under nitrogen protection filtrate is filled in the non-PVC composite co-extruding film transfusion bag, sealing was sterilized 30 minutes for 115 ℃; namely get 40 bags, every bag of 250ml.
Embodiment 4
A kind of pharmaceutical composition of amino acid, wherein proline C
5H
9NO
21.00kg, serine C
3H
7NO
31.00kg, alanine C
3H
7NO
22.00kg, isoleucine C
6H
13NO
23.52kg, leucine C
6H
13NO
24.90kg, Aspartic Acid C
4H
7NO
42.50kg, tyrosine C
9H
11NO
30.25kg, glutamic acid C
5H
9NO
40.75kg, phenylalanine C
9H
11NO
25.33kg, arginine hydrochloride C
6H
14N
4O
2HCL5.00kg, lysine hydrochloride C
6H
14N
2O
2HCL 4.30kg, valine C
5H
11NO
23.60kg, threonine C
4H
9NO
32.50kg, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 2.50kg, tryptophan C
11H
12N
2O
20.90kg, methionine C
15H
11NO
2S 2.25kg, cystine C
6H
12N
2O
4S
20.10kg, glycine C
2H
5NO
27.60kg, antioxidant 1-sulfo-sorbitol 0.0344kg, maleic acid 0.0206kg.
Aforementioned pharmaceutical compositions is that supplementary material is prepared into injection; preparation method: get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride; when treating that medicinal liquid is cooled to 50 ℃, add tryptophan, when treating that medicinal liquid is cooled to 45 ℃; add cystine; add until completely dissolved the antioxidant of recipe quantity to fully dissolving, inject water to 1000L, uniform stirring; 0.45 μ m filter element; 0.22 μ m filter element filtering; under nitrogen protection filtrate is filled in the non-PVC composite co-extruding film transfusion bag, sealing was sterilized 30 minutes for 115 ℃; namely get 4000 bags, every bag of 250ml.
Embodiment 5
A kind of pharmaceutical composition of amino acid, wherein proline C
5H
9NO
21.00kg, serine C
3H
7NO
31.00kg, alanine C
3H
7NO
22.00kg, isoleucine C
6H
13NO
23.52kg, leucine C
6H
13NO
24.90kg, Aspartic Acid C
4H
7NO
42.50kg, tyrosine C
9H
11NO
30.25kg, glutamic acid C
5H
9NO
40.75kg, phenylalanine C
9H
11NO
25.33kg, arginine hydrochloride C
6H
14N
4O
2HCL5.00kg, lysine hydrochloride C
6H
14N
2O
2HCL 4.30kg, valine C
5H
11NO
23.60kg, threonine C
4H
9NO
32.50kg, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 2.50kg, tryptophan C
11H
12N
2O
20.90kg, methionine C
15H
11NO
2S 2.25kg, cystine C
6H
12N
2O
4S
20.10kg, glycine C
2H
5NO
27.60kg, antioxidant 1-sulfo-sorbitol 0.0324kg, maleic acid 0.0226kg.
Aforementioned pharmaceutical compositions is that supplementary material is prepared into injection; preparation method: get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride; when treating that medicinal liquid is cooled to 50 ℃, add tryptophan, when treating that medicinal liquid is cooled to 45 ℃; add cystine; add until completely dissolved the antioxidant of recipe quantity to fully dissolving, inject water to 1000L, uniform stirring; 0.45 μ m filter element; 0.22 μ m filter element filtering; under nitrogen protection filtrate is filled in the non-PVC composite co-extruding film transfusion bag, sealing was sterilized 30 minutes for 115 ℃; namely get 4000 bags, every bag of 250ml.
Embodiment 6
A kind of pharmaceutical composition of amino acid, wherein proline C
5H
9NO
21.00kg, serine C
3H
7NO
31.00kg, alanine C
3H
7NO
22.00kg, isoleucine C
6H
13NO
23.52kg, leucine C
6H
13NO
24.90kg, Aspartic Acid C
4H
7NO
42.50kg, tyrosine C
9H
11NO
30.25kg, glutamic acid C
5H
9NO
40.75kg, phenylalanine C
9H
11NO
25.33kg, arginine hydrochloride C
6H
14N
4O
2HCL5.00kg, lysine hydrochloride C
6H
14N
2O
2HCL 4.30kg, valine C
5H
11NO
23.60kg, threonine C
4H
9NO
32.50kg, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 2.50kg, tryptophan C
11H
12N
2O
20.90kg, methionine C
15H
11NO
2S 2.25kg, cystine C
6H
12N
2O
4S
20.10kg, glycine C
2H
5NO
27.60kg, antioxidant 1-sulfo-sorbitol 0.0306kg, maleic acid 0.0244kg.
Aforementioned pharmaceutical compositions is that supplementary material is prepared into injection; preparation method: get water for injection; heated and boiled; evacuation; inflated with nitrogen; drop into successively supplementary material 70 ℃-90 ℃ of water temperatures: tyrosine; leucine; isoleucine; valine; methionine; phenylalanine; Aspartic Acid; glutamic acid; arginine hydrochloride; lysine hydrochloride; threonine; serine; proline; glycine; alanine; simultaneously cooling; when treating that medicinal liquid is cooled to 60 ℃; add histidine monohydrochloride; when treating that medicinal liquid is cooled to 50 ℃, add tryptophan, when treating that medicinal liquid is cooled to 45 ℃; add cystine; add until completely dissolved the antioxidant of recipe quantity to fully dissolving, inject water to 1000L, uniform stirring; 0.45 μ m filter element; 0.22 μ m filter element filtering; under nitrogen protection filtrate is filled in the non-PVC composite co-extruding film transfusion bag, sealing was sterilized 30 minutes for 115 ℃; namely get 4000 bags, every bag of 250ml.
Claims (8)
1. the pharmaceutical composition of an amino acid is characterized in that: proline C
5H
9NO
20.90-1.10 weight portion, serine C
3H
7NO
30.90-1.10 weight portion, alanine C
3H
7NO
21.90-2.10 weight portion, isoleucine C
6H
13NO
23.40-3.60 weight portion, leucine C
6H
13NO
24.80-5.00 weight portion, Aspartic Acid C
4H
7NO
42.40-2.60 weight portion, tyrosine C
9H
11NO
30.20-0.30 weight portion, glutamic acid C
5H
9NO
40.70-0.80 weight portion, phenylalanine C
9H
11NO
25.20-5.40 weight portion, arginine hydrochloride C
6H
14N
4O
2HCL 4.90-5.10 weight portion, lysine hydrochloride C
6H
14N
2O
2HCL 4.20-4.40 weight portion, valine C
5H
11NO
23.50-3.70 weight portion, threonine C
4H
9NO
32.40-2.60 weight portion, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 2.40-2.60 weight portion, tryptophan C
11H
12N
2O
20.80-1.00 weight portion, methionine C
15H
11NO
2S 2.20-2.30 weight portion, cystine C
6H
12N
2O
4S
20.10 weight portion, glycine C
2H
5NO
27.50-7.70 weight portion, pharmaceutic adjuvant 0.04-0.07 weight portion.
2. the pharmaceutical composition of a kind of amino acid according to claim 1, wherein proline C
5H
9NO
21.00 weight portion, serine C
3H
7NO
31.00 weight portion, alanine C
3H
7NO
22.00 weight portion, isoleucine C
6H
13NO
23.52 weight portion, leucine C
6H
13NO
24.90 weight portion, Aspartic Acid C
4H
7NO
42.50 weight portion, tyrosine C
9H
11NO
30.25 weight portion, glutamic acid C
5H
9NO
40.75 weight portion, phenylalanine C
9H
11NO
25.33 weight portion, arginine hydrochloride C
6H
14N
4O
2HCL 5.00 weight portions, lysine hydrochloride C
6H
14N
2O
2HCL 4.30 weight portions, valine C
5H
11NO
23.60 weight portion, threonine C
4H
9NO
32.50 weight portion, histidine monohydrochloride C
6H
9N
3O
2HCLH
2O 2.50 weight portions, tryptophan C
11H
12N
2O
20.90 weight portion, methionine C
15H
11NO
2S 2.25 weight portions, cystine C6H
12N
2O
4S
20.10 weight portion, glycine C
2H
5NO
27.60 weight portion, pharmaceutic adjuvant 0.055 weight portion.
3. the pharmaceutical composition of a kind of amino acid according to claim 1 and 2, wherein medicinal adjuvant is 1-sulfo-sorbitol in the pharmaceutical composition, or 1-sulfo-sorbitol and maleic acid.
4. the pharmaceutical composition of a kind of amino acid according to claim 1 and 2 is prepared into ejection preparation.
5. the application of the pharmaceutical composition of a kind of amino acid according to claim 1 and 2 in the medicine of the hypoproteinemia that serious amino acid starvation disease that preparation treatment operation, severe trauma, large-area burns cause and various diseases cause.
6. the pharmaceutical composition of a kind of amino acid according to claim 3, wherein the weight ratio of 1-sulfo-sorbitol and maleic acid is 1: 0.5-0.8.
7. the pharmaceutical composition of a kind of amino acid according to claim 6, wherein the weight ratio of 1-sulfo-sorbitol and maleic acid is 1: 0.60.
8. the pharmaceutical composition of a kind of amino acid according to claim 6, wherein the weight ratio of 1-sulfo-sorbitol and maleic acid is 1: 0.70.
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|---|---|---|---|
| CN201210384542.4A CN102861011B (en) | 2012-10-12 | 2012-10-12 | Medicine composition of 18 amino acids and preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108289835A (en) * | 2015-09-28 | 2018-07-17 | Apr应用制药研究股份公司 | Modified release orally administered amino acid formulations |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101357118A (en) * | 2008-09-26 | 2009-02-04 | 郑飞雄 | Medicine composition containing 15 kinds of amino acid and preparation method thereof |
| 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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2012
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101357118A (en) * | 2008-09-26 | 2009-02-04 | 郑飞雄 | Medicine composition containing 15 kinds of amino acid and preparation method thereof |
| 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 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108289835A (en) * | 2015-09-28 | 2018-07-17 | Apr应用制药研究股份公司 | Modified release orally administered amino acid formulations |
| CN108289835B (en) * | 2015-09-28 | 2022-04-15 | Apr应用制药研究股份公司 | Modified release orally administered amino acid formulations |
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| Publication number | Publication date |
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| CN102861011B (en) | 2014-11-05 |
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