CN1370524A - Lovamin and its prepn process - Google Patents
Lovamin and its prepn process Download PDFInfo
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- CN1370524A CN1370524A CN 02112730 CN02112730A CN1370524A CN 1370524 A CN1370524 A CN 1370524A CN 02112730 CN02112730 CN 02112730 CN 02112730 A CN02112730 A CN 02112730A CN 1370524 A CN1370524 A CN 1370524A
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Abstract
The present invention belongs to one mixed amino acid injection containing 18 kinds of amino acids and is named Lovamin. Its main components includes 18 kinds of amino acids in 8.5 wt% or 11.4 wt%, sulfite in 0.001-0.003 wt% and glacial acetic acid in small amount other than injection water. Its preparation process includes the steps of compounding of injection, filling and disinfecting in a steam sterilizer. Compared with similar product, the present invention has less side effect.
Description
Technical field
The invention belongs to a kind of Amino Acid Compound Injection that contains 18 seed amino acids---be commonly called as Novamin and manufacture method thereof.
Background technology
Protein is to form cyto-architectural main component, is biocatalyst, and is the important regulating and controlling person of gene expression.The elementary cell of protein structure is an aminoacid.Human body need be taken in a certain amount of protein every day satisfying the needs of vital movement, when can't just importing Freamine from vein and be replenished when gastrointestinal tract be taken in q.s because of certain reason.The Amino Acid Compound Injection that contains 18 seed amino acids is very important amino acid supplements, plays an important role clinically.
Aminoacid is very unstable in solution, and is very easily oxidized and produce the harmful material of a series of complexity.From the sixties in 20th century amino acid put into production use, for guaranteeing the stability of product, must add sulphite compounds, as sodium sulfite, sodium pyrosulfite etc. with unique antioxidant properties.Because people did not understand the harm of this class material to human body at that time, thereby manufacturing enterprise is for guaranteeing the stability of product, and without stint adds in a large number usually.Yet from the eighties in 20th century, along with the development of clinical pharmacy, pharmacology and medical science, people begin to recognize the side effect of sulfites material and carried out comparatively deep research aspect the safeties 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 clinically relevant side reaction is a sulphite allergy, and symptom is a bronchospasm, stridulates dyspnea, pernicious, laryngeal edema, hypotension, shock even death.
Research to the aspects such as pharmacology, molecular biology, toxicology and drug interaction of sulphite has also confirmed reality and the potential danger of sulfites as the infusion products antioxidant.
Sulphite has special drug interaction in amino acid transfusion.The Freamine that contains sulphite can cause the degraded of some vitamin, and the speed of degraded has substantial connection with the concentration of sulphite.As adding thiamine in the amino acid injection that contains the 500mg/l sodium sulfite, room temperature storage is after 24 hours, almost all degradeds, and VB1 and folic acid are 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 especially suspect the toxic action of 6 kinds of converted products of tryptophan to the human liver, because test find to accept to contain the hepatocyte tissue of rat of the Freamine injection of sulphite variation has taken place, all fatty infiltrations of its liver enzyme, bilirubin and portal vein all have and increase.The decline that the observed common indication of energy is blood plasma mesobilirubin and amino transaminase on human body.
The influence of sulphite to multiple living matter also found in research.The irreversible reaction of the cystine linkage in sulphite and DNA (deoxyribonucleic acid) (DNA), the plain nucleotide of adenine, vitaminK-3, 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, sulphite is familiar with more fully to the side effect of human body.It is limited one after another in medicine and Application in Food in countries in the world for this reason.Permission daily intaking amount (ADI) as sulphite in foods is restricted to about 0.7mg SO in western countries
2/ kg body weight, the people who is equivalent to 70 kilogram weights takes in 80 milligrams of sodium sulfitees.China is to containing the 300-500 milligram in the per 1000 milliliters of products of being defined as of compound recipe 18 amino acid injection Central Asia sulphates contents, and international standard is also basic identical.
Per day for adults need be imported 500-1000 milliliter amino acid injection can satisfy physiological need.With the sodium sulfite that contains 500mg/l in the Freamine is example, is forced to simultaneously to have accepted Duo 6～7 times sulphite than oral permission intake in that 1000 milliliters of inputs are amino acid whose.Therefore, patient and doctor selection in the face of facing a difficult choice: or for the generation that reduces side effect reduces the dosage of Freamine, but curative effect can not guarantee; For guaranteeing curative effect, accept to know deleterious too much sulphite perfectly well, thereby face the danger of side effect.This situation has limited the clinical practice of this important medicine of Amino Acid Compound Injection greatly.
Why the drug quality national standard does not do stricter control to the content of sulphite, basic reason is the superior oxidation resistance that this material can not be substituted, under the prior art condition, also can't produce and do not contain or contain the few Amino Acid Compound Injection of sulphite.
Summary of the invention
The objective of the invention is to develop a kind of novel Amino Acid Compound Injection---Novamin and manufacture method thereof, in this injection, the content of sulphite is controlled in seldom the safety range, makes this injection be reduced to bottom line to the side effect of human body.
Its main technical schemes is that the main component of described Novamin is: contain 8.5% or 11.4% compound recipe 18 seed amino acids, contain sulphite and the micro-glacial acetic acid of 0.001-0.003%, all the other compositions are water for injection.Unit is the weight percentage by volume.
Described sulphite is sodium sulfite or sodium pyrosulfite, and can form the anionic sulfites material of bisulfite in aqueous solution.
A kind of method feature of making Novamin is: a, preparation, in container, add 85 grams or pulverous compound recipe 18 seed amino acids of 114 grams, 0.01～0.03 gram sulphite, open vacuum pump, make the interior vacuum of container reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure, and repeatable operation 3 times, make the interior oxygen content of container be lower than 0.1%, constantly filling nitrogen, be under the barotropic state, in container, adding the glacial acetic acid of water for injection 940 grams or 921 grams and trace to keep container;
B, embedding, the above-mentioned solution for preparing after filtering, 0.22 micron filter is poured in the suitable infusion bottle, must be in filtration and embedding with nitrogen protection with starvation, adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue again to infusion bottle, after press aluminium lid, must not ingress of air at whole embedding process herb liquid;
Steam autoclave is adopted in c, sterilization, sterilizes 10～40 minutes down at 115～125 ℃.
Name of product of the present invention is a Novamin, is a kind of Amino Acid Compound Injection that contains 18 seed amino acids.According to amino acid whose concentration in the product, be divided into and contain aminoacid 8.5% and 11.4% two kind of specification, be i.e. Novamin 8.5% and Novamin 11.4%.Novamin and existing market are sold and the difference of the like product that uses is that the content of wherein contained sulfites antioxidant only is 1/50th to 1/10th of like product, thereby have better safety, lower side effect.
Meaning of the present invention has been invented a kind of sulphite content well below national standard, and safe enough is arranged, and can be the compound recipe 18 seed amino acid injection of the fine tolerance of patient.In this product, the content of sulphite is 0.001-0.003%, promptly contains the 10-30 milligram in 1000 ml solns, is equivalent to 50 to 1/10th of national standard.In 1000 milliliters of this product of per day for adults input, the intake of sulphite only is the 10-30 milligram, far below the day permission intake of 80 milligrams in developed country.Thereby improved security of products widely.Patient can accept sufficient dosage this product treatment and needn't worry to take place toxic and side effects, life and the quality of life that guarantees patient had significant meaning.
Creativeness of the present invention is that this product is not to replace sulphite with another kind of antioxidant simply, but fundamentally solved the key reason that influences amino acid injection stability---the influence of oxygen, thus solved a puzzlement amino acid injection manufacturing industry difficult problem for many years.The inventor finds under study for action, if 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.Therefore, although product solution is sealed in the infusion bottle, extraneous oxygen can't enter, and product can constantly decompose, and can't use until rotten.
Oxygen content when the addition of experiment discovery sulphite begins with production in the production system is directly related.Production system comprises all raw materials, the production equipment that contacts with product and packaging material.We be sure of that the unique antioxidation of sulphite in Freamine just is to stop inspiring or interrupt it and carrying out automatically of chemical reaction thus.As long as the oxygen in the 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, therefore still must add the sulphite of 0.001-0.003%, to stop inspiring of reaction according to practical situation.Also may further reduce its dosage under the experiment condition, but, there is no need to do further improvement because this dosage to the human body safe enough, can be applied to suitability for industrialized production as early as possible for making invention.
The prescription and the production method of Novamin are described below.
The prescription contrast of Novamin and existing product is as follows.
Per 1000 milliliters of products contain:
| Composition | Novamin 8.5% | Novamin 11.4% | Compound recipe 18 amino acid injections |
| 18 seed amino acids such as L-alanine | 85 grams | 114 grams | 85 or 114 grams |
| Sulphite (sodium sulfite or sodium pyrosulfite | 0.01-0.03 gram | 0.01-0.03 gram | 0.3-0.5 gram |
| Glacial acetic acid | 2.5 milliliter | 2.75 milliliter | 2.5-2.75 milliliter |
| Water for injection | 940 grams | 921 grams | The 940-921 gram |
Wherein 18 seed amino acids such as L-alanine are main active, the aminoacid that provides human body to need.
Sulphite (sodium sulfite or sodium pyrosulfite etc.) is antioxidant, and protection aminoacid oxidation Decomposition not the stability of product is played a crucial role, but itself has side effect to human body.
Glacial acetic acid is the pH regulator agent, and product is had and the suitable pH value of human body.
Water for injection is solvent, is used to dissolve various raw materials to form injection.
Novamin is compared with other compound recipe 18 amino acid injections, and key difference is that the content of sulphite is significantly different, and the content in the Novamin is lower 10 to 50 times than other products.Because the unique effect of sulphite in product, make Novamin in the safety of clinical use, be better than other products far away, greatly expand the scope of application and the clinical safety dosage of Amino Acid Compound Injection, in the production of aminoacid product and clinical practice, had epoch making significance.
The specific embodiment
Example one contains 8.5%, 1000 milliliter of the Novamin of 0.001% sodium sulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 85 grams |
| Sodium sulfite | 0.01 gram |
| Glacial acetic acid | 2.5 milliliter |
| Water for injection | 940 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.01 gram sodium sulfitees such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 940 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 121 ℃ of sterilizations 12 minutes.
Example two contains 8.5%, 1000 milliliter of the Novamin of 0.002% sodium sulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 85 grams |
| Sodium sulfite | 0.02 gram |
| Glacial acetic acid | 2.5 milliliter |
| Water for injection | 940 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.02 gram sodium sulfitees such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 940 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 125 ℃ of sterilizations 10 minutes.
Example three contains 8.5%, 1000 milliliter of the Novamin of 0.003% sodium sulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 85 grams |
| Sodium sulfite | 0.03 gram |
| Glacial acetic acid | 2.5 milliliter |
| Water for injection | 940 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.03 gram sodium sulfitees such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 940 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 115 ℃ of sterilizations 40 minutes.
Example four contains 11.4%, 1000 milliliter of the Novamin of 0.001% sodium sulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 114 grams |
| Sodium sulfite | 0.01 gram |
| Glacial acetic acid | 2.75 milliliter |
| Water for injection | 921 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.01 gram sodium sulfitees such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 921 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 120 ℃ of sterilizations 15 minutes.
Example five contains 11.4%, 1000 milliliter of the Novamin of 0.002% sodium sulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 114 grams |
| Sodium sulfite | 0.02 gram |
| Glacial acetic acid | 2.75 milliliter |
| Water for injection | 921 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.02 gram sodium sulfitees such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 921 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 118 ℃ of sterilizations 20 minutes.
Example six contains 11.4%, 1000 milliliter of the Novamin of 0.003% sodium sulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 114 grams |
| Sodium sulfite | 0.03 gram |
| Glacial acetic acid | 2.75 milliliter |
| Water for injection | 921 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.03 gram sodium sulfitees such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 921 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 119 ℃ of sterilizations 16 minutes.
Example seven contains 8.5%, 1000 milliliter of the Novamin of 0.001% sodium pyrosulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 85 grams |
| Sodium pyrosulfite | 0.01 gram |
| Glacial acetic acid | 2.5 milliliter |
| Water for injection | 940 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.01 gram sodium pyrosulfite such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 940 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 121 ℃ of sterilizations 12 minutes.
Example eight contains 8.5%, 1000 milliliter of the Novamin of 0.002% sodium pyrosulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 85 grams |
| Sodium pyrosulfite | 0.02 gram |
| Glacial acetic acid | 2.5 milliliter |
| Water for injection | 940 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.02 gram sodium pyrosulfite such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 940 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 124 ℃ of sterilizations 11 minutes.
Example nine contains 8.5%, 1000 milliliter of the Novamin of 0.003% sodium pyrosulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 85 grams |
| Sodium pyrosulfite | 0.03 gram |
| Glacial acetic acid | 2.5 milliliter |
| Water for injection | 940 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.03 gram sodium pyrosulfite such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 940 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 122 ℃ of sterilizations 13 minutes.
Example ten contains 11.4%, 1000 milliliter of the Novamin of 0.001% sodium pyrosulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 114 grams |
| Sodium pyrosulfite | 0.01 gram |
| Glacial acetic acid | 2.75 milliliter |
| Water for injection | 921 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.01 gram sodium pyrosulfite such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 921 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 116 ℃ of sterilizations 35 minutes.
Example 11 contains 11.4%, 1000 milliliter of the Novamin of 0.002% sodium pyrosulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 114 grams |
| Sodium pyrosulfite | 0.02 gram |
| Glacial acetic acid | 2.75 milliliter |
| Water for injection | 921 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.02 gram sodium pyrosulfite such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 921 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 122 ℃ of sterilizations 14 minutes.
Example 12 contains 11.4%, 1000 milliliter of the Novamin of 0.003% sodium pyrosulfite
Prescription:
| Composition | Quantity |
| 18 seed amino acids such as L-alanine | 114 grams |
| Sodium pyrosulfite | 0.03 gram |
| Glacial acetic acid | 2.75 milliliter |
| Water for injection | 921 grams |
Production method:
1. preparation
The capacity of getting is 2000 to 3000 milliliters a three-necked bottle, is associated with vacuum system, nitrogen pipeline, the water for injection pipeline of the control of band valve respectively, and is furnished with magnetic stirring apparatus.In this three-necked bottle, add 18 seed amino acids, 0.03 gram sodium pyrosulfite such as the pulverous L-alanine of 85 grams.Open vacuum pump, make a bottle interior vacuum reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure.Repeatable operation three times guarantees that oxygen content is lower than 0.1% in the bottle.Guaranteeing constantly to fill nitrogen, keeping direct draught in the bottle and add anaerobic water for injection 921 grams.Dissolved oxygen content must not be higher than 0.1ppm in the water for injection.Stirring and dissolving, and constantly fill nitrogen.Add 2.5 milliliters of glacial acetic acid.The solution preparation is finished.
2. embedding
Solution pours in the suitable infusion bottle after 0.22 micron filter filters.Must be in filtration and the embedding with nitrogen protection with starvation.Adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue to infusion bottle.After press aluminium lid.Attention must not ingress of air at whole embedding process herb liquid.
3. sterilization
Adopt steam autoclave, 115 ℃ of sterilizations 30 minutes.
Claims (3)
1, a kind of Novamin is characterized in that the composition of this Novamin is: contain 8.5% or 11.4% compound recipe 18 seed amino acids, contain sulphite and the micro-glacial acetic acid of 0.001-0.003%, all the other compositions are water for injection, and unit is the weight percentage by volume.
2, Novamin according to claim 1 is characterized in that sulphite is sodium sulfite or sodium pyrosulfite and can forms the anionic sulfites material of bisulfite in aqueous solution.
3, the manufacture method of Novamin according to claim 1 is: a, preparation, in container, add 85 grams or pulverous compound recipe 18 seed amino acids of 114 grams, 0.01～0.03 gram sulphite, open vacuum pump, make the interior vacuum of container reach-0.085～-0.09 MPa, charge into purity and be 99.999% nitrogen to normal pressure, and repeatable operation 3 times, make the interior oxygen content of container be lower than 0.1%, constantly filling nitrogen, be under the barotropic state, in container, adding the glacial acetic acid of water for injection 940 grams or 921 grams and trace to keep container;
B, embedding, the above-mentioned solution for preparing after filtering, 0.22 micron filter is poured in the suitable infusion bottle, must be in filtration and embedding with nitrogen protection with starvation, adopt the tamponade equipment of band evacuation-fill nitrogen function to jump a queue again to infusion bottle, after press aluminium lid, must not ingress of air at whole embedding process herb liquid;
Steam autoclave is adopted in c, sterilization, sterilizes 10～40 minutes down at 115～125 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021127301A CN1189167C (en) | 2002-03-06 | 2002-03-06 | Lovamin and its prepn process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021127301A CN1189167C (en) | 2002-03-06 | 2002-03-06 | Lovamin and its prepn process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1370524A true CN1370524A (en) | 2002-09-25 |
| CN1189167C CN1189167C (en) | 2005-02-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021127301A Expired - Lifetime CN1189167C (en) | 2002-03-06 | 2002-03-06 | Lovamin and its prepn process |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302489A (en) * | 2011-07-14 | 2012-01-04 | 青岛华仁药业股份有限公司 | Preparation method of compound amino acid injection |
| CN102743378A (en) * | 2012-07-30 | 2012-10-24 | 李慧 | Composition containing eighteen amino acids |
| CN103340853A (en) * | 2013-06-21 | 2013-10-09 | 广东利泰制药股份有限公司 | Compound 18-amino acid injection containing little amount of antioxidant and preparation method thereof |
-
2002
- 2002-03-06 CN CNB021127301A patent/CN1189167C/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302489A (en) * | 2011-07-14 | 2012-01-04 | 青岛华仁药业股份有限公司 | Preparation method of compound amino acid injection |
| CN102743378A (en) * | 2012-07-30 | 2012-10-24 | 李慧 | Composition containing eighteen amino acids |
| CN103340853A (en) * | 2013-06-21 | 2013-10-09 | 广东利泰制药股份有限公司 | Compound 18-amino acid injection containing little amount of antioxidant and preparation method thereof |
| CN103340853B (en) * | 2013-06-21 | 2014-12-10 | 广东利泰制药股份有限公司 | Compound 18-amino acid injection containing little amount of antioxidant and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1189167C (en) | 2005-02-16 |
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Address after: 214092 No. 16 North Gate Road, Mashan, Jiangsu, Wuxi Patentee after: Fresenius Cabi Huarui Pharmaceutical Co. Ltd. Address before: 214092 No. 16 North Gate Road, Mashan, Jiangsu, Wuxi Patentee before: Sino-Swed Pharmaceutical Co., Ltd. |
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