CN1565450A - Naloxone Hydrochloride Injection and its preparation method - Google Patents
Naloxone Hydrochloride Injection and its preparation method Download PDFInfo
- Publication number
- CN1565450A CN1565450A CN 03143204 CN03143204A CN1565450A CN 1565450 A CN1565450 A CN 1565450A CN 03143204 CN03143204 CN 03143204 CN 03143204 A CN03143204 A CN 03143204A CN 1565450 A CN1565450 A CN 1565450A
- Authority
- CN
- China
- Prior art keywords
- injection
- naloxone hydrochloride
- add
- sodium
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a Naloxone hydrochloride injection and powder injection, and the process for preparation, wherein middle aperture fiber film hyperfiltration technology is employed to remove the impurities, thus diminishing the damage of main medicaments and improving the quality of products.
Description
Technical field
The present invention relates to a kind of opiate receptor pure antagonist, have medicine-naloxone hydrochloride injecting medicine-feeding form with the complete opposite pharmacological action of morphine and preparation method thereof.
Background technology
Naloxone hydrochloride (Naloxone hydrochloride) is the opiate receptor specific antagonist, not exciting this receptor itself, but with the affinity of this receptor greater than morphine and enkephalin, can block or replace combining of opioid and endogenous opiatepeptide and receptor competitively, remove morphine class drug intoxication, the inhibition of antagonism respiratory center, and waken effect.China's Ministry of Public Health is ratified its little liquid drugs injection in nineteen ninety, and (specification: 1ml: 0.4mg) go on the market, be used for morphine class combined anesthesia medicine postoperative with intramuscular injection or intravenous injection mode, remove respiration inhibition, waken and acute alcoholism, each consumption is no more than 1.2 mg.But over this product was gone on the market surplus in the of 10 year, clinical effectiveness was good, and its indication and usage and dosage also have bigger variation than the scope of nineteen ninety Ministry of Public Health approval.Clinical use shows that this medicine using priciple is emphasized " continuing medication in early days, in right amount, ".Table 1 has gathered present clinical indication and the usage and dosage of naloxone hydrochloride.Because this product only has little liquid drugs injection (specification: 1ml: 0.4mg) for clinical use so far, often to from several even tens of ampoules, get liquid to be used for injection, or add in the transfusion with intravenous drip, complex operation not only, and increased greatly that medicine contacts with air and other vessel and the chance polluted, thereby make user produce infusion reaction,, even jeopardize patient's life as symptoms such as having a fever, feel sick, feel cold, heart beating is unusual.As seen present naloxone hydrochloride dosage form and dosage specification bring very big inconvenience and medical hidden danger for numerous doctors and patient, and are difficult to meet this medicine using priciple.
Little liquid drugs injection clinical indication of table 1. naloxone hydrochloride and usage and dosage
| Purposes | Usage and dosage |
| Cerebral ischemia/cerebral infarction | 2.0-4.0 milligram adds 5% glucose or 250 milliliters of intravenous drips of 0.9% sodium chloride transfusion, 2 times on the one, the 10-15 days course of treatment. |
| Subarachnoid space/cerebral hemorrhage | 2.0-4.0 milligram adds 5% glucose or 0.9% sodium chloride transfusion vein instils, 10 days courses of treatment. |
| Dizzy | 0.4-0.8 milligram/day, intramuscular injection.Or add the injection of 20-40 milliliter 50% glucose injection medium-sized vein, 0.4-0.8 milligram/day, 3 days courses of treatment. |
| Sudden deafness | Add 5% glucose or 0.9% sodium chloride transfusion iv drip, 0.8 milligram/day, 20 days courses of treatment. |
| Craniocerebral injury | 1. intravenous drip: 28 milligrams/day, change 14 milligrams/day into after 3 days, change 7 milligrams/day into after 7 days; 2. intrathecal injection: 2.0-4.0 milligram/day; 3. lavation in the art: flushing is 2-3 time in 20 milliliter of 0.9% sodium chloride injection of 10-20 milligram adding. |
| Acute spinal cord injury | First dose 5.4 milligrams, intravenous injection (finishing in 15 minutes); After 45 minutes, 0.28 milligram/hour, intravenous drip was kept 23 hours; Later 4-6 milligram/day, intravenous drip. |
| Stupor | The 0.8-2.0 milligram adds quiet notes in 20 milliliter of 5% glucose first, adds with 4 milligrams subsequently and keeps quiet in the 250-50 milliliter glucose infusion liquid until clear-headed. |
| Cardio-pulmonary-cerebral resuscitation | In the cardio-pulmonary resuscitation process, in case venous access foundation, 2.0 milligrams of quiet notes as early as possible.Later per 30 minutes 2.0 milligrams of quiet notes.The child is cut down according to the circumstance. |
| Shock | The first dose of quiet notes of 0.8-2.0 milligram, then the 2-8 milligram adds in 250 milliliters of glucose infusion liquids quiet, press the low adjustment of hypertension. |
| Respiratory failure | Acute: 0.8-2.0 milligram vein is slowly injected, and repeats once in per 2 hours or until breathing steadily according to the state of an illness.Chronic: 2.0 milligrams add 250 milliliter of 0.9% sodium chloride transfusion iv drip, every day 2 times, 10 days courses of treatment. |
| Pulmonary encephalopathy | The first dose of quiet notes/intramuscular injection of 0.4-1.2 milligram can repeat once after 30 minutes, and the 1.6-3.2 milligram is kept quiet. |
| Opium poisping | 0.4-0.8 milligram/2 hours quiet notes are until clear-headed. |
| Tranquilizing soporific class medicine is poisoned | Slight 0.4-0.8 milligram, severe 0.8-2.0 milligram, intramuscular injection or slow quiet notes. |
| Organophosphor severe | Respiration inhibition person adds with 1.2 milligrams of quiet notes.3 per hour quiet notes 0.8-1.2 milligrams in case of necessity are until clear-headed. |
| Acute alcoholism | Slightly: 0.4 milligram, quiet notes; Moderate: the quiet notes of 0.4-0.8 milligram; Severe: the first dose of quiet notes of 0.8-1.6 milligram, quiet again notes 0.4-0.8 milligram after 0.5 hour is until clear-headed. |
| The psychosis acute poisoning | 0.8-10 milligram, quiet notes, intramuscular injection or subcutaneous injection were kept 7 days. |
| The general anesthesia postoperative wakens | 0.2-0.8 quiet notes of milligram or go into kettle and drip soon. |
| Acute pancreatitis | Edema: add in 500 milliliter of 5% glucose infusion liquid quiet, 2.0-4.0 milligram/day, 7 days courses of treatment; Hemorrhagic necrosis: add in 500 milliliter of 5% glucose infusion liquid quiet, 2.0-4.0 milligram/day, 14 days courses of treatment. |
| Withdrawal | 0.8-2 milligram/day, quiet notes, intramuscular injection or subcutaneous injection, 7 days courses of treatment. |
Summary of the invention
The present invention only has little liquid drugs injection at existing naloxone hydrochloride injection just, and (specification: 1ml: 0.4mg) dosage form, the defective that is difficult to meet clinical needs provides that a kind of property easy to use, safe is good, steady quality, naloxone hydrochloride injection type evident in efficacy.Pharmaceutical dosage form of the present invention is naloxone hydrochloride injection (each basic packing unit is 5 milliliters to 500 milliliters, hydrochloric Allylnoroxymorphone 0.4-10 milligram) and powder ampoule agent for injection (every hydrochloric Allylnoroxymorphone 0.4-10 milligram).
Injection of the present invention is the aqueous solution for injection of naloxone hydrochloride, wherein can contain in sodium chloride, potassium chloride, sodium lactate, xylitol, sorbitol, maltose, glucose, fructose, dextran or the glycine etc. one or more with as osmotic pressure regulator; Can contain simultaneously one or more and EDTA disodium, EDTA calcium sodium or the two use in conjunction in sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, the vitamin C etc. as stabilizing agent.
Injectable powder of the present invention can contain one or more in mannitol, sorbitol and/or sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, the vitamin C etc., and one or more (pH value that every finished powder pin is added after the dissolving of 10 milliliters of waters for injection are 3.0～5.0) in the alkali-metal phosphate of monovalence, acetate, carbonate and hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid and each seed amino acid, to play dispersion, hydrotropy or effect such as stable.
50 milliliters of infusion solutions to 500 milliliters of specifications in the injection of the present invention can be directly used in venoclysis, have stopped potential safety hazard; 5 milliliters to 40 milliliters injection, because of drug loading increases greatly, injection in the time of can being directly used in intrathecal injection or other and need increasing dosage, do not need from several the little liquid drugs injections of low dosage, to get it filled to be used for injection, thereby avoided the secondary pollution of medication process, and because of its volume is little, be easy to packing and transportation, can reduce the cost of its production and transportation greatly; Injectable powder of the present invention, be dissolved in appropriate solvent during use, not only can be used for venoclysis, but also can be used for intramuscular injection, subcutaneous injection and intrathecal injection, flexible and convenient to use, applicable to the various situations in the table 1, and significantly reduced loss and inconvenience in drug packaging, the transportation, simultaneously in use with the touch opportunity of air and other vessel much smaller than the little liquid drugs injection of existing naloxone hydrochloride, greatly reduce potential safety hazard.
In a word, the drug loading of medicine of the present invention and form of administration, remedied the deficiency that the little liquid drugs injection of existing naloxone hydrochloride can not satisfy its clinical indication and usage and dosage needs far away, more can meet the principle of medication that naloxone hydrochloride " continues medication " in early days, in right amount,, and naloxone hydrochloride is in solid state in the injectable powder, also makes stability of drug obviously be better than existing little aqueous injection.Cost an arm and a leg because of this product crude drug simultaneously, in the preparation process, containing drug solns adopts mesopore fibrous membrane ultrafiltration new technique to remove impurity, not only reduced the absorption of needle-use activated carbon to effective ingredient, remove the impurity effect and be better than needle-use activated carbon, improved product quality, and, made its stability obviously improve because of the minimizing of impurity in the product.No matter be injection or injectable powder, its quality and stability all are better than existing little aqueous injection.
Therefore say, though the present invention's manufacture method is easy, based on prior art, but obtained beyond thought good result, more meet the using priciple that naloxone hydrochloride " continues medication " in early days, in right amount,, and, further reduced safety of clinical administration hidden danger because of having improved product quality and stability.
The preparation method of the injection of the present invention of Ti Chuing is in view of the above: prepare isotonic agent or additives concentrated wiring liquid 1.: get isotonic agent, stabilizing agent etc. and add 3 times of amount waters for injection, stirring and dissolving, add 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride and add 20 times of amount waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add to the full amount of water for injection again,, measure intermediate content and pH value with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, qualified after 0.22 μ m filtering with microporous membrane, fill, conventional sterilization, pack the qualified back of quality inspection.
The preparation method of the injectable powder of the present invention of Ti Chuing is in view of the above: get naloxone hydrochloride and add 20 times of amount waters for injection, stirring makes dissolving, add 10～100 times dispersant, stirring and dissolving, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 the degerming of μ m microporous filter membrane, fill, lyophilization get lyophilized injectable powder.
When the present invention prepared injection, the isoosmotic adjusting agent of adding can be that in sodium chloride, potassium chloride, sodium lactate, xylitol, sorbitol, maltose, glucose, fructose, dextran or the glycine etc. one or more are united use.The additives that add can be stabilizing agent such as antioxidant, the complexing of metal ion agent etc. on the pharmaceutics, and antioxidant can be that in sodium pyrosulfite (0.1%～0.2%), sodium sulfite (0.1%～0.2%), sodium thiosulfate (0.1%), cysteine hydrochloride (0.00015%～0.05%), TGA (0.005%), methionine (0.05%～0.1%), the vitamin C (0.2%) etc. one or more are united use; The complexing of metal ion agent can be EDTA disodium, EDTA calcium sodium or the two use in conjunction.
When the present invention prepares injectable powder, before the filter membrane degerming, remove and in medicinal liquid, add dispersant (as mannitol, sorbitol etc., 10～100 times of principal agent amount) outside, also can add antioxidant (as sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, in the vitamin C etc. one or more are united use, the same injection of consumption) and pH regulator agent (the alkali-metal phosphate of monovalence, acetate, carbonate or its aqueous solution and hydrochloric acid, acetic acid, sulphuric acid, in phosphoric acid and each seed amino acid one or more mix to use, and making every finished powder pin add 10 milliliters of pH value after the waters for injection dissolving is 3.0～5.0) wait the additives on the pharmaceutics to stablize or effects such as dispersion to play.Technological process also can be under aseptic condition, after the filter membrane degerming, uses the deep bid lyophilization earlier, is sub-packed in the cillin bottle after crushed.
Preparation method of the present invention is simple, general, is fit to industrialized great production.Injection or injectable powder product meet every requirement of injection.In addition, all up to specification through its hemolytic test sensitivity test of animal experiment and local irritation test.
1. the external hemolytic test of naloxone hydrochloride chloride injection:
1.1 test material:
1.1.1 test sample: naloxone hydrochloride chloride injection (specification: 50ml: naloxone hydrochloride 8mg and sodium chloride 0.45g, lot number: 020406)
1.1.2 control sample: 0.9% sodium chloride injection lot number: 030422 is produced by Siyao Co., Ltd., Shijiazhuang.
1.1.3 animal: Japan large ear rabbit, body weight 2.5 ± 0.2kg is provided by Hebei province's Experimental Animal Center.
1.2 test method
1.2.1 the preparation of red cell suspension: get rabbit, from heart extracting blood 10ml, put triangular flask (in bead is arranged) jolting, defibrinate to remove, add chlorination sodium injection 20ml, stir, centrifugal (2000rpm) 5 minutes removes supernatant, add chlorination sodium injection 20ml again, centrifugal, the same method operation is the water white transparency shape until supernatant for several times repeatedly, takes off layer erythrocyte and is made into 2% red blood cell suspension with sodium chloride injection.
1.2.2 operating procedure:
Get 7 test tubes, add 2% red blood cell suspension, sodium chloride injection, naloxone hydrochloride sodium chloride injection and sterilized water respectively by table 3.Each pipe jog is even, put 37 ℃ of insulation 1h, observe and write down 0.25,0.5,0.75,1,2,3, each pipe situation of 4hr, judge its result by table 2 standard.
Table 2, hemolytic test be criterion as a result
The contents of a project
Full haemolysis solution is red for clarification, and the no erythrocyte in test tube bottom is residual
Part haemolysis solution is clarification redness or peony, and the test tube bottom has a small amount of erythrocyte residual
The cohesion erythrocyte does not break, but cohesion occurs, and erythrocyte can not redispersion after the jolting
No lyse red blood cell all sinks, the supernatant achromaticity and clarification
Table 3, hemolytic test result
Pipe numbers 1234567
2% red blood cell suspension (ml) 2.5 2.5 2.5 2.5 2.5 2.5 2.5
0.9% sodium chloride injection (ml) 2.0 2.1 2.2 2.3 2.4 2.5 0
Naloxone hydrochloride sodium chloride injection (ml) 0.5 0.4 0.3 0.2 0.1 00
Sterilized water (ml) 0000000
As a result 0.25h------+
0.5h???????????-????-????-????-????-????-?????+
0.75h??????????-????-????-????-????-????-?????+
1.0h???????????-????-????-????-????-????-?????+
2.0h???????????-????-????-????-????-????-?????+
3.0h???????????-????-????-????-????-????-?????+
4.0h???????????-????-????-????-????-????-?????-
(illustrate :-: be no haemolysis, no coagulation; +: be haemolysis or coagulation)
1.2.3 result:
As seen from Table 2,1-5 number pipe be for test sample, manages negative contrast No. 6, manages positive contrast No. 7,1-6 number the pipe supernatant is colourless, and erythrocyte sinks, and erythrocyte disperses again after the jolting, no haemolysis, No. 7 red and clarifications of pipe solution, the no erythrocyte in test tube bottom, all haemolysis.
1.2.4 conclusion: naloxone hydrochloride sodium chloride injection 0.1-0.5ml does not produce haemolysis and cohesion to erythrocyte in 4h, have good blood compatibility.It is generally acknowledged: person's injection for intravenous is used but the 0.3ml injection does not produce the haemolysis in 2h.
2. hypersensitive test:
2.1 test material:
2.1.1 test sample: the naloxone hydrochloride chloride injection, the same
2.1.2 reference substance: 0.9% sodium chloride injection is the same
Egg white solution: new fresh hen egg (commercially available), get Ovum Gallus domesticus album, to filter, filtrate adds equivalent physiologic dose brine dilution.
2.1.3 animal: Cavia porcellus: outbreeding group strain, male and female half and half are provided by Hebei province's Experimental Animal Center.
2.2 test method:
Get 18 of healthy guinea pigs, be divided into 3 groups at random, 6 every group, male and female half and half are respectively administration group, normal saline group and positive controls (egg white solution).Lumbar injection naloxone hydrochloride sodium chloride injection 0.5ml next day of the administration treated animal, totally 3 times, be divided into two groups of A, B then, A organizes the fortnight after injection first, attack for reagent 2ml by vena femoralis injection, observing animal has or not anaphylaxiss such as grabbing nose, perpendicular hair, dyspnea, spasm, shock even death, B to organize after injecting first the 21st day to attack and observe with method; Negative control group and positive controls are injected and are observed with method.
2.3 result:
Twice intravenous reaction of Cavia porcellus sees Table 4, and all in back 15 minutes of injection, anaphylaxis progression is 0 for naloxone hydrochloride sodium chloride injection and normal saline; And behind the double injection positive control egg white solution 15 minutes, allergic phenomenas such as perpendicular hair, dyspnea, tic and death all appear in 6 Cavia porcelluss, and anaphylaxis progression is 4 grades.
Table 4, hypersensitive test result
Anaphylaxis progression
Group animal attack time (my god) 01234
Normal saline group 1 14 0
2????????14?????????0
3????????14?????????0
4????????21?????????0
5????????21?????????0
6????????21?????????0
Naloxone hydrochloride 1 14 0
Change sodium injection group 2 14 0
3????????14?????????0
4????????21?????????0
5????????21?????????0
6????????21?????????0
Egg white solution group 1 14 4
2????????14?????????????????????????????4
3????????14?????????????????????????????4
4????????21?????????????????????????????4
5????????21?????????????????????????????4
6????????21?????????????????????????????4
Annotate: grade scale: 0 grade: no significant reaction
1 grade: only have and slightly grab nose, tremble or erect hair
2 grades: cough is several times arranged, grab nose or perpendicular hair
3 grades: repeatedly or continuously cough, with dyspnea or spasm, tic etc.
4 grades: spasm, tic, gatism, shock
2.4 conclusion: the test of naloxone hydrochloride sodium chloride injection systemic anaphylaxis, animal do not have any anaphylaxis and take place, and anaphylaxis progression is 0 grade.
3. blood vessel irritation test:
3.1 test material
3.1.1 test sample: the naloxone hydrochloride chloride injection, the same.
Reference substance: 0.9% sodium chloride injection, the same.
3.1.2 animal: rabbit is the same.
3.2 test method:
Get 6 of healthy rabbits, male and female half and half, from rabbit left side auricular vein injection naloxone hydrochloride sodium chloride injection, dosage is 10ml/kg by the sterile working; Auris dextra edge intravenous injection sodium chloride injection, dosage is 10ml/kg, once a day, injects continuously 6 days.Last was injected back 24 hours, observed the injection site and had or not erythema, edema.Then rabbit is put to death, respectively ear injection site, rabbit left and right sides front end 2-3cm is cut, the tissue of getting comprises auricular vein, uses 10% formaldehyde fixed, routine pathology section, dyeing, light microscopy checking.
3.3 result:
Injected back 24 hours at last, skin erythema and edema are not seen in the perusal injection site.Pathological section is the result show, test sample and reference substance injection back rabbit ear edge vein there is no irritant reaction such as blood vessel injury, tissue degeneratiaon or necrosis.
3.4 conclusion:
Intravenous injection naloxone hydrochloride sodium chloride injection does not produce obvious irritation to rabbit auricular vein blood vessel.So think that this product local excitation test is up to specification.
4. injection quality control index of the present invention
[character] this product is colourless or almost colourless clear liquid.
[discriminating] is the positive reaction of naloxone hydrochloride and hydrochlorate.
[inspection] pH value: 3.5～7.5.
Related substance: adopt the HPLC-Self-control method to measure, impurity content must not cross 0.5%.
Aseptic: press two appendix XI of Chinese Pharmacopoeia version in 2000 H check, should be up to specification.
Bacterial endotoxin: press two appendix XI of Chinese Pharmacopoeia version in 2000 E check, should be up to specification.
Other: should meet every requirement by two appendix I of Chinese Pharmacopoeia version in 2000 B injection general rule.
[assay] adopts HPLC-external standard method, hydrochloric Allylnoroxymorphone (C
19H
21NO
4HCl) should be 90.0～110.0% of labelled amount.
5. injectable powder quality control index of the present invention
[character] this product is the lyophilizing block or the powder of white or off-white color.
[discriminating] is the positive reaction of naloxone hydrochloride and hydrochlorate.
[inspection] pH value: get this product,, survey pH value, should be 3.0～5.0 with 10 milliliters of cold distilled water dissolvings of newly boiling.
Related substance: adopt the HPLC-Self-control method to measure, impurity content must not cross 0.5%.
Aseptic: press two appendix XI of Chinese Pharmacopoeia version in 2000 H check, should be up to specification.
Bacterial endotoxin: press two appendix XI of Chinese Pharmacopoeia version in 2000 E check, should be up to specification.
Other: should meet every requirement by two appendix I of Chinese Pharmacopoeia version in 2000 B injection general rule.
[assay] adopts HPLC-external standard method, hydrochloric Allylnoroxymorphone (C
19H
21NO
4HCl) should be 90.0～110.0% of labelled amount.
6. stability of drug products of the present invention is investigated the result:
According to Chinese Pharmacopoeia version in 2000 two appendix XI XC " medicine stability guideline " requirement, to medicine of the present invention and commercially available little liquid drugs injection 6 months (being equivalent to room temperature 2 years) of accelerated test under 40 ℃ of conditions, stablizing contrast and investigate, the results are shown in Table 5.As seen, medicine stability of the present invention is better than commercially available little liquid drugs injection.
The result is investigated in the contrast of table 5 naloxone hydrochloride injection accelerated test
| Sample | The examination project | Standing time (moon) | ||||
| ??0 | ??1 | ??2 | ????3 | ????6 | ||
| Powder pin (1.6mg) | Outward appearance | White lyophilizing block | White lyophilizing block | White lyophilizing block | White lyophilizing block | White lyophilizing block |
| PH value | ??4.36 | ??4.27 | ??4.30 | ??4.36 | ??4.38 | |
| Clarity | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Related substance (%) | ??0.04 | ??0.04 | ??0.06 | ??0.05 | ??0.06 | |
| Naloxone hydrochloride content (%) | ??99.41 | ??99.52 | ??100.07 | ??99.13 | ??99.57 | |
| Transfusion (250ml: 1.2mg) | Outward appearance | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid |
| PH value | ??4.11 | ??4.14 | ??4.15 | ??4.31 | ??4.38 | |
| Clarity | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| 5-HMF (trap) | ??0.121 | ??0.129 | ??0.128 | ??0.132 | ??0.137 | |
| Related substance (%) | ??0.08 | ??0.06 | ??0.07 | ??0.08 | ??0.09 | |
| Naloxone hydrochloride content (%) | ??99.65 | ??99.72 | ??98.56 | ??98.04 | ??97.85 | |
| Glucose content (%) | ??99.67 | ??99.25 | ??98.84 | ??98.84 | ??98.42 | |
| Liquid drugs injection (20ml: 2 mg) | Outward appearance | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid |
| PH value | ??3.92 | ??3.93 | ??3.93 | ??4.03 | ??3.93 | |
| Clarity | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Related substance (%) | ??0.07 | ??0.08 | ??0.06 | ??0.08 | ??0.07 | |
| Naloxone hydrochloride content (%) | ??100.83 | ??99.81 | ??98.98 | ??98.52 | ??98.22 | |
| Commercially available little liquid drugs injection (1ml: 0. 4mg) | Outward appearance | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid | Colourless transparent liquid |
| PH value | ??4.52 | ??4.93 | ??5.03 | ??5.12 | ??5.33 | |
| Clarity | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | |
| Related substance (%) | ??0.40 | ??0.87 | ??1.72 | ??2.14 | ??3.76 | |
| Naloxone hydrochloride content (%) | ??100.83 | ??98.81 | ??98.18 | ??95.52 | ??93.22 | |
The specific embodiment
Embodiment 1:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sodium chloride 900mg 900g
Water for injection adds to 100ml 100L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 900 grams, add 2700 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.2 grams, add 24 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 100 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 2:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 0.4mg 0.4g
Glucose 5g 5000g
Sodium thiosulfate 0.1g 100g
EDTA calcium sodium 0.01g 10g
Water for injection adds to 100ml 100L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get glucose 5000 grams, sodium thiosulfate 100 grams and EDTA calcium sodium 10 grams, add 15000 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through the excellent filtering decarbonization of sand filtration, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 0.4 gram, add 8 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 100 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 3:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 0.8mg 0.8g
Sodium chloride 900mg 900g
Water for injection adds to 50ml 50L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 900 grams, add 2700 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 0.8 gram, add 16 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 50 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 4:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.6mg 1.6g
Glucose 2.5g 2500g
Sodium sulfite 0.05g 50g
EDTA disodium 0.005g 5g
Water for injection adds to 50ml 50L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get glucose 2500 grams, sodium sulfite 50 grams and EDTA calcium sodium 5 grams, add 15000 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through the excellent filtering decarbonization of sand filtration, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.6 grams, add 32 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 50 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 5:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 0.4mg 0.4g
Sodium chloride 2.25g 2250g
Vitamin C 0.5g 500g
EDTA calcium sodium 0.025g 25g
Water for injection adds to 250ml 250L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 2250 grams, vitamin C 500 grams and EDTA calcium sodium 25 grams, add 15000 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through the excellent filtering decarbonization of sand filtration, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 0.4 gram, add 8 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 250 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 6:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Mannitol 20g 20000g
Sodium sulfite 0.1g 100g
EDTA calcium sodium 0.01g 10g
Water for injection adds to 100ml 100L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get mannitol 20000 grams, sodium sulfite 100 grams and EDTA calcium sodium 10 grams, add 600000 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through the excellent filtering decarbonization of sand filtration, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.2 grams, add 24 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 100 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 7:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sodium chloride 450mg 450g
Water for injection adds to 50ml 50L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 450 grams, add 1350 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.2 grams, add 24 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 50 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 8:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sodium chloride 1800mg 1800g
Water for injection adds to 200ml 200L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 1800 grams, add 5400 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.2 grams, add 24 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 200 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 9:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sodium chloride 2250mg 2250g
Water for injection adds to 250ml 250L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 2250 grams, add 6750 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.2 grams, add 24 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 250 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 10:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sodium chloride 4500mg 4500g
Water for injection adds to 500ml 500L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 4500 grams, add 13500 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.2 grams, add 24 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 500 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 11:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sodium chloride 900mg 900g
Water for injection adds to 100ml 100L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 900 grams, add 2700 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.2 grams, add 24 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 100 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 12:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 0.8mg 0.8g
Glucose 12.5g 12500g
Water for injection adds to 250ml 250L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get glucose 12500 grams, add 37500 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 0.8 gram, add 16 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 250 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 13:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 0.8mg 0.8g
Mannitol 40mg 40g
Preparation method: get naloxone hydrochloride 0.8g, add 16g water for injection, stirring makes dissolving, with mannitol 40g, add water for injection 300ml, stirring and dissolving is with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 the degerming of μ m microporous filter membrane, 1000 of fills, lyophilization get lyophilized injectable powder.
Embodiment 14:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sorbitol 120mg 120g
Preparation method: get naloxone hydrochloride 1.2g, add 24g water for injection, stirring makes dissolving, adds sorbitol 120g, adds water for injection 500ml, stirring and dissolving, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 μ m microporous filter membrane degerming, 1000 of fills, lyophilization gets lyophilized injectable powder.
Embodiment 15:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sorbitol 40mg 40g
Preparation method: get naloxone hydrochloride 1.2g, add 24g water for injection, stirring makes dissolving, adds sorbitol 40g, adds water for injection 300ml, stirring and dissolving, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 μ m microporous filter membrane degerming, 1000 of fills, lyophilization gets lyophilized injectable powder.
Embodiment 16:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.6mg 1.6g
Sorbitol 25mg 25g
Mannitol 25mg 25g
Preparation method: get naloxone hydrochloride 1.6g, add 32g water for injection, stirring makes dissolving, add sorbitol 25g, mannitol 25g, add water for injection 300ml, stirring and dissolving is with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 the degerming of μ m microporous filter membrane, 1000 of fills, lyophilization get lyophilized injectable powder.
Embodiment 17:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 0.4mg 0.4g
Mannitol 40mg 40g
Preparation method: get naloxone hydrochloride 0.4g, add 8g water for injection, stirring makes dissolving, with mannitol 40g, adds water for injection 300ml, stirring and dissolving, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 μ m microporous filter membrane degerming, deep bid lyophilization are pulverized, 1000 of packing get lyophilized injectable powder.
Embodiment 18:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 10mg 10g
Sorbitol 25mg 25g
Mannitol 35mg 35g
Preparation method: get naloxone hydrochloride 10g, add 200g water for injection, stirring makes dissolving, adds sorbitol 25g, mannitol 35g, adds water for injection 200ml, stirring and dissolving, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 μ m microporous filter membrane degerming, deep bid lyophilization are pulverized, 1000 of packing get lyophilized injectable powder.
Embodiment 19:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 4mg 4g
Sorbitol 120mg 120g
Preparation method: get naloxone hydrochloride 4g, add 80g water for injection, stirring makes dissolving, add sorbitol 120g, add water for injection 500ml, stirring and dissolving is with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 the degerming of μ m microporous filter membrane, 1000 of fills, lyophilization get lyophilized injectable powder.
Embodiment 20:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 8mg 8g
Sodium chloride 450mg 450g
Water for injection adds to 50ml 50L
Preparation method: 1. prepare the isotonic agent concentrated wiring liquid: get sodium chloride 450 grams, add 1350 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 8 grams, add 160 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution being merged, add injection water to 50 liter again, is 4.5 with the hydrochloric acid adjust pH, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 21:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.2mg 1.2g
Sodium thiosulfate 5mg 5g
EDTA calcium sodium 0.05mg 0.05g
Water for injection adds to 5ml 5L
Preparation method: 1. prepare the additives concentrated wiring liquid: get sodium thiosulfate 5 grams and EDTA calcium sodium 0.05 gram, add 15 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.2 grams, add 24 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 5 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 22:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 4mg 4g
Sodium pyrosulfite 0.02g 20g
EDTA calcium sodium 2mg 2g
Water for injection adds to 20ml 20L
Preparation method: 1. prepare the additives concentrated wiring liquid: get sodium pyrosulfite 20 grams and EDTA calcium sodium 2 grams, add 66 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 4 grams, add 80 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 20 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 23:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.6mg 1.6g
Vitamin C 0.04g 40g
EDTA calcium sodium 0.002g 2g
Water for injection adds to 20ml 20L
Preparation method: 1. prepare the additives concentrated wiring liquid: get vitamin C 40 grams and EDTA calcium sodium 2 grams, add 126 gram waters for injection, stirring and dissolving, adding 0.3% needle-use activated carbon boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly get 2. preparation naloxone hydrochloride concentrated wiring liquids: get naloxone hydrochloride 1.6 grams, add 32 gram waters for injection, stirring makes dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 20 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Embodiment 24:
The present embodiment prescription is as follows:
Per 1000 consumptions of per 1 consumption
Naloxone hydrochloride (is pressed C
19H
21NO
4The HCl meter) 1.6mg 1.6g
TGA 0.5mg 0.5g
EDTA calcium sodium 1mg 1g
Water for injection adds to 10ml 10L
Preparation method: 1. prepare the additives concentrated wiring liquid: get TGA 0.5 gram and EDTA calcium sodium 1 gram, add 45 gram waters for injection, stirring and dissolving adds 0.3% needle-use activated carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2. prepare the naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride 1.6 grams, add 32 gram waters for injection, stir and make dissolving, promptly.3. above-mentioned two solution are merged, add injection water to 10 liter again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, 1000 of fills, conventional sterilization, the qualified back of quality inspection packing.
Claims (6)
1, a kind of injecting medicine-feeding form of naloxone hydrochloride is characterized in that principal agent is the injection or the powder ampoule agent for injection of naloxone hydrochloride.
2, the injecting medicine-feeding form of naloxone hydrochloride according to claim 1, each the basic packing unit that it is characterized in that said injection is 5 milliliters to 500 milliliters, hydrochloric Allylnoroxymorphone 0.4-10 milligram; Every hydrochloric Allylnoroxymorphone 0.4-10 milligram of said injectable powder.
3, the injecting medicine-feeding form of naloxone hydrochloride according to claim 1 and 2 is characterized in that can containing in the said injection a kind of in sodium chloride, potassium chloride, sodium lactate, xylitol, sorbitol, maltose, glucose, fructose, dextran or the glycine or several make isoosmotic adjusting agent; Can also contain one or more and EDTA disodium and/or EDTA calcium sodium used as stabilizers in sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, the vitamin C.
4, the injecting medicine-feeding form of naloxone hydrochloride according to claim 1 and 2, it is characterized in that in the said injectable powder also having mannitol and/or sorbitol, and can contain in one or more and/or the alkali-metal phosphate of monovalence, acetate, carbonate or its aqueous solution and hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid and the aminoacid in sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, the vitamin C one or more.
5, the preparation method of the injecting medicine-feeding form of claim 1 or 2 described naloxone hydrochlorides, it is characterized in that this method may further comprise the steps: 1.. preparation isotonic agent or additives concentrated wiring liquid: get isotonic agent, stabilizing agent etc. and add 3 times of amount waters for injection, stirring and dissolving, adding 0.3% needle-use activated carbon boiled 30 minutes, through sand filtration rod filtering decarbonization, promptly; 2.. preparation naloxone hydrochloride concentrated wiring liquid: get naloxone hydrochloride and add 20 times of amount waters for injection, stir and make dissolving, promptly.3.. above-mentioned two solution are merged, add to the full amount of water for injection again, with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, measure intermediate content and pH value, qualified after 0.22 μ m filtering with microporous membrane, fill, conventional sterilization, the qualified back of quality inspection packing gets injection.The naloxone hydrochloride concentrated wiring liquid adds the dispersant of 10～100 times of amounts, stirs, and makes dissolving, and with hollow fiber ultrafiltration membrane (aperture is not more than 100,000) ultrafiltration, 0.22 μ m microporous filter membrane degerming, fill, lyophilization get lyophilized injectable powder.
6, according to the preparation method of the injecting medicine-feeding form of the described naloxone hydrochloride of claim 5, when it is characterized in that making injectable powder, medicinal liquid through the deep bid lyophilization, after the pulverizing, is filled into cillin bottle again after the filter membrane degerming.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03143204 CN1565450A (en) | 2003-06-27 | 2003-06-27 | Naloxone Hydrochloride Injection and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03143204 CN1565450A (en) | 2003-06-27 | 2003-06-27 | Naloxone Hydrochloride Injection and its preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1565450A true CN1565450A (en) | 2005-01-19 |
Family
ID=34471297
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03143204 Pending CN1565450A (en) | 2003-06-27 | 2003-06-27 | Naloxone Hydrochloride Injection and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1565450A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021012686A1 (en) * | 2019-07-19 | 2021-01-28 | 广东奇方药业有限公司 | Naloxone hydrochloride injection and preparation method therefor |
-
2003
- 2003-06-27 CN CN 03143204 patent/CN1565450A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021012686A1 (en) * | 2019-07-19 | 2021-01-28 | 广东奇方药业有限公司 | Naloxone hydrochloride injection and preparation method therefor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1174557A (en) | Keratan sulfate oligosaccharide fraction and drug containing the same | |
| CN1671367A (en) | Aqueous 2,6-diisopropylphenol pharmaceutical compositions | |
| CN1915222A (en) | Composition of liposome, and preparation method | |
| CN101049324A (en) | Composition of medication prepared from ginkgo leaves and puerarin | |
| CN1565450A (en) | Naloxone Hydrochloride Injection and its preparation method | |
| CN101058567A (en) | Novel pharmacology acceptable salt for cinepazide | |
| CN100341492C (en) | Ginseng-astragalus blood-sugar lowering soft capsule, and its preparing and detecting method | |
| CN1739561A (en) | Application of high permeability medicine composition in preparing pre-nacrosis medicine | |
| CN1709269A (en) | Medicinal composition containing polydatin and its use | |
| CN1615296A (en) | Carboxamidine derivatives and their use in the treatment of vascular diseases | |
| CN101049293A (en) | Medication composition of acetyl cysteine or its pharmaceutical salt and asarin | |
| CN1876004A (en) | A medicament for treating cerebrovascular disease | |
| CN1709436A (en) | Yinzhihuang tablet of oriental wormwood, cape jasmine and baicalin, and its preparing and detecting method | |
| CN101058565A (en) | Stable cinepazide water-soluble salt | |
| CN1857200A (en) | Medicinel liquid containing proton pump inhibitor | |
| CN1190223C (en) | Recipe of Chinese medicine with treating and health care functions | |
| CN1709238A (en) | Power for intravenous injection with liver-protecting action, and its preparation and quality control method | |
| CN1533806A (en) | Liver cell growing promotor injection and its preparation method and application | |
| CN1493289A (en) | Hydroxy camptothecin emulsion and its preparation method | |
| CN1895219A (en) | Bendalysine eye gel preparation and its making method | |
| CN1586604A (en) | Zedoary injection preparation and its preparing method | |
| CN1194678C (en) | Tiopronin freeze-dried powder injection | |
| CN1235580C (en) | Total gambogic acid preparation and its preparing method | |
| CN1034570C (en) | Tri-lower alkoxy benzene derivatives | |
| CN1175817C (en) | Oral liquid of sodium fructose-biphosphate and preparing process thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |