CN101716137A - Entecavir injection - Google Patents
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- CN101716137A CN101716137A CN200910220604A CN200910220604A CN101716137A CN 101716137 A CN101716137 A CN 101716137A CN 200910220604 A CN200910220604 A CN 200910220604A CN 200910220604 A CN200910220604 A CN 200910220604A CN 101716137 A CN101716137 A CN 101716137A
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- entecavir
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Abstract
The invention relates to an Entecavir injection comprising a small-capacity injection, a large-capacity sterilized injection and a freeze-dry sterile powder injection. The Entecavir injection is characterized by being prepared from 0.1-2.5mg of single-dosage active Entecavir and an additive which comprises a solvent for injection, 0-10% of pH regulator, 0-10% of antioxidant, 0-60% of solubilizer, 0-20% of isotonic regulator, 0.1-20% of filler and 0.1-20% of filling scaffold agent, and the percentage is the percent of the total quality of the injection in the liquid volume. The Entecavir comprises the injection and the sterile powder injection and has favorable inhibited effect on hepatitis B and good stability.
Description
Technical field
The present invention relates to injection of a kind of Entecavir and preparation method thereof, specifically, be that intravital sterile solution, emulsion or suspension are injected in a kind of confession of being made by the Entecavir of activity form, and for facing with the solution that before is made into or the sterilized powder or the concentrated solution of suspension.
Background technology
Entecavir (Entecavir) is a kind of guanosine analog, chemistry 2-amino-9-[(1S by name, and 3R, 4S)-and 4-hydroxyl-3-methylol-2-methylene cyclopenta]-1,9-dihydro-6H-purine-6-one, molecular structural formula is as follows:
Molecular formula C
12H
15N
5O
3, molecular weight 277.3 contains a water of crystallization usually, its monohydrate molecular formula C
12H
15N
5O
3.H
2O, molecular weight 295.3.
U.S. Pat 5,206,244 disclose Entecavir and its purposes at the treatment hepatitis B.International publication WO98/09964 and WO2004,052310 disclose the synthetic method of two kinds of improved Entecavirs respectively.U.S. Patent application US-2001-0033864-A1 and PCT patent application WO 01/64421A1 disclose the preparation compositions that contains the low dosage Entecavir.
Hepatitis B virus (hepatitis B virus, HBV) infecting is a global health problem, the HBV chronic infection can cause chronic hepatitis B (chronic hepatitis B, CHB), liver cirrhosis (livercirrhosis, LC), and primary hepatoma (hepatocellulor carcinoma HCC) waits relevant disease.
Entecavir is a kind of 2 '-penta ring NSC 22837 analog of being developed in the nineties in 20th century by U.S. Shi Guibao company, its initial purpose is used for treating herpes simplex infections, finds that afterwards it has very strong anti-HBV ability and toxicity is relatively very low.Entecavir has very strong anti-HBV effect, to HBV, dna replication dna initial, reverse 3 stages such as disease and DNA normal chain is synthetic and all play inhibitory action, the action target spot of Entecavir is archaeal dna polymerase and the sick enzyme of counter-rotating of HBV, by suppressing these enzymes, thereby gene RNA reverses sick DNA minus strand of duplicating HBV before suppressing, and then suppress the synthetic of normal chain, thereby the extension and the assembling of the DNA chain of blocking-up HBV.
Entecavir is a kind of antiviral agent efficiently, and clinical research has shown that to the hepatitis B virus good inhibition effect because the activity of Entecavir hepatitis B virus is very high, low-down dosage just can reach the desired therapeutic effect.The pharmaceutical preparation of the Entecavir of listing is peroral dosage form both at home and abroad at present, as tablet and oral liquid, feed can cause the delay to the Entecavir absorption, and then cause malabsorption and declined bioavailability of oral administration, therefore this type of peroral dosage form is answered (medicine) being taken before meal usefulness, at least before the meal or latter two hour of eating take just and can reach drug absorption preferably.
Summary of the invention
The object of the present invention is to provide a kind of entecavir injection, comprise sterile solution and for facing lyophilized injectable powder or concentrated solution with preceding wiring solution-forming.
The technical scheme that adopts is:
Entecavir injection comprises small-volume injection, high capacity sterilization injection and freeze dry sterile powder injection, it is characterized in that this medicine is to add additives by the active Entecavir 0.1-2.5mg of single dose to be prepared into; Additives comprise solvent for injection, pH regulator agent 0-10%, antioxidant 0-10%, solubilizing agent 060%, etc. open regulator 0-20%, filler 0.120%, filling bracket agent 0.120%, above-mentioned percentage ratio accounts for the percentage ratio of liquor capacity for this medicine gross mass.
Described injection with small volume, be to add additives by active Entecavir to be prepared into, wherein active Entecavir solution concentration is 0.005-2.5mg/ml, pH regulator agent 0～10% in the additives, antioxidant 0～10%, solubilizing agent 0～60%, above-mentioned percentage ratio account for the percentage ratio of liquor capacity for this medicine gross mass.
Described high capacity sterile solution for injection is to add additives by active Entecavir to be prepared from, wherein active Entecavir solution concentration is that 0.005-0.5mg/ml, pH regulator agent are about 0～10%, antioxidant 0～10%, etc. open about 0%～20%, the solubilizing agent 0～60% of regulator, above-mentioned percentage ratio accounts for the percentage ratio of liquor capacity for this medicine gross mass.
Described freeze dry sterile powder injection is to be thought to be prepared into solution for the Ka Weijia additives by activity, packing, lyophilization forms, before the packing in the solution: the active Entecavir concentration of principal agent is that 0.005-2.5mg/ml, pH regulator agent are about 0～10%, filler 0.1-20%, filling bracket agent 0.1%～20%, antioxidant 0～10%, and above-mentioned percentage ratio accounts for the percentage ratio of liquor capacity for this medicine gross mass.
The preparation method of entecavir injection is:
1, process for preparation of injection of the present invention is: getting active Entecavir solution concentration is 0.0052.5mg/ml, add pH regulator agent 0～10%, antioxidant 0～10%, solubilizing agent about 0～60% and solvent for injection, heat, stir, take off charcoal, fine straining, fill, high temperature sterilize is made the sterilization injection with small volume.
2, process for preparation of injection of the present invention is: getting active Entecavir solution concentration is 0.005-2.5mg/ml, pH regulator agent 0～10%, antioxidant 0～10%, etc. open that regulator is about 0～20%, solubilizing agent 0～60%, solvent for injection, heat, stir, take off charcoal, fine straining, fill, high temperature sterilize is made the sterilization high-capacity injection.
3, process for preparation of injection of the present invention is: getting active Entecavir solution concentration is 0.005-2.5mg/ml, the pH regulator agent is about 0～10%, filler 0.1-20%, filling bracket agent 0.1%～20%, antioxidant 0～10%, solvent for injection, filter, the freeze dry sterile powder injection of injection is made in packing, lyophilization.
Described " active Entecavir " comprising: Entecavir and solvate thereof, hydrate, monocrystalline type, polymorphic, mixed crystal type, armorphous; The officinal salt that also comprises Entecavir, the biological effectiveness of finger reservation parent compound and characteristic, have with the pharmacological action of Entecavir equivalence, pharmaceutically acceptable medicinal acid addition salt, the hydrochlorate that for example comprises Entecavir, mesylate, oxalates, acetate, lactate, gluconate, tartrate, citrate, fumarate, succinate, malate, maleate, benzoate, and the solvate of above-mentioned salt, hydrate, monocrystalline type, polymorphic, mixed crystal type, the biological salts substances of armorphous Entecavir derivant, or the like.The above-described existence form that all is Entecavir as active component.
Solvent as injection of the present invention can be water for injection and non-water-soluble matchmaker, non-water-soluble matchmaker can be divided into oiliness solvent and the non-water-soluble matchmaker of water solublity, and the oiliness solvent comprises injection vegetable oil, ethyl oleate, triacetyl glycerine, ethyl acetate, ethyl carbonate, ethyl lactate, acetic acid butyl propionate, benzyl benzoate, Semen Myristicae isopropyl alcohol ester etc.The non-water-soluble matchmaker of water solublity comprises alcohols, for example ethanol, glycerol, propylene glycol, 1,3 butylene glycol, Macrogol 200, Liquid Macrogol, PEG400, Polyethylene Glycol 1600, phenylpropanol etc.; Amide-type, for example dimethyl formamide, dimethyl acetylamide, just-(beta-hydroxyethyl) lactamide, N, N-diethyl lactamide, N, N-diethyl-2-picolinamide etc.; The dioxolanes class, for example formal glycerine, 4-methylol-1,3-dioxolanes, 5-hydroxyl-1,3-dioxolanes, 2,2-dimethyl-1,3-dioxolanes-4-methanol etc. and sulfoxide class etc.
As the additives of injection of the present invention have antioxidant, metal chelating agent, noble gas, solubilising cosolvent, growth of microorganism inhibitor, pH regulator agent, etc. open regulator, analgesic, filling bracket agent etc.
The antioxidant of injection comprises sulfites antioxidant among the present invention, as sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, sodium formaldehyde sulphoxylate, sodium dithionite etc.; Thio-compounds is as thioglycerin, thiourea, 2 mercapto ethanol, dimercaptopropanol, BAL, 1-sulfo-sorbitol etc.; Polyatomic phenol is as hydroquinone, para-aminophenol, oxine etc.; Its acids of ammonia is as L-cysteine hydrochloride, L-methionine, L-lysine, L-propylhomoserin, L-arginine, L-leucine, L-isoleucine, L-tryptophan, L-glutathion etc.; Other classes, as in ethylenediaminetetraacetic acid, disodium edta, succinic acid, citric acid, hydroquinone, malic acid, ascorbic acid, sodium ascorbate, inositol, alpha-tocopherol, α-tocopheryl acetate, xylitol, the D-xylose one or more etc.
Metal chelating agent in the injection of the present invention comprises dicarboxylic acid compounds such as disodiumedetate, citric acid, tartaric acid.
Noble gas in the injection of the present invention comprises gases such as nitrogen, argon, neon, krypton and carbon dioxide; Flocculating agent comprises benzyl alcohol, phenethanol etc.
Growth of microorganism inhibitor in the injection of the present invention comprises bromo geramine 0.01%, phemerol chloride 0.01%, benzyl alcohol 1.0%, chlorobutanol 0.5%, chlorocresol 0.1% to 0.25%, cresol 0.3%, methyl hydroxybenzoate 0.18%, propylparaben 0.02%, phenol 0.5%, nitric acid or phenylmercuric acetate 0.02%, thimerosal 0.01%, phenethanol 0.25% to 0.5% etc.
PH regulator agent in the injection of the present invention comprises mineral acid and organic acid, and wherein mineral acid has sulphuric acid, hydrochloric acid, phosphoric acid and phosphate buffer, acetate buffer etc. according to Professional knowledge other mineral acids as can be known; Organic acid comprises acetic acid, lactic acid, methanesulfonic acid, citric acid, maleic acid and according to Professional knowledge other organic acid as can be known.
PH regulator agent in the injection of the present invention can also comprise all kinds of inorganic bases and organic base, wherein inorganic base comprises sodium hydroxide, potassium hydroxide and according to Professional knowledge other inorganic bases as can be known, organic base comprises triethanolamine and according to Professional knowledge other organic bases as can be known, preferred sodium hydroxide.
Grade in the injection of the present invention is opened regulator, comprises 5% glucose solution and 0.9% sodium chloride solution.
Filler in the injection of the present invention or filling bracket agent comprise one or more the mixture in lactose, sucrose, glucose, mannitol, sodium dihydrogen phosphate, sodium chloride, sodium hydrogen phosphate, cysteine, gelatin hydrolysate, glycine, sorbitol, calcium lactobionate., dextran, the polyvinylpyrrolidone.
Analgesic in the injection of the present invention comprises benzyl alcohol 1%, chlorobutanol 0.25% to 0.5%, procaine hydrochloride 0.5% to 2%, lignocaine 0.5% to 1.0%, urethane 6.25% etc.
Result of the present invention shows, injection steady quality of the present invention, and quality standard is controlled.Its detection index and method are as follows:
Related substance detects:
Related substance mainly is initiation material, intermediate, the side reaction product of bringing in the production process, and the catabolite in the storage etc.Its content back is answered pharmaceutical purity.
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is packed column; With the acetonitrile-water is mobile phase, and the detection wavelength is 254nm, and column temperature is a room temperature.
Algoscopy: test sample is made into need testing solution and contrast solution.Precision is measured contrast solution and is injected chromatograph of liquid, regulates detection sensitivity, makes the peak height of main constituent chromatographic peak be about 20% of full scale, and precision is measured above-mentioned two kinds of solution injection chromatograph of liquid again, and the record chromatogram is to 2 times of main constituent peak retention time.In the chromatogram of need testing solution as show impurity peaks, measure each impurity peak area and with the single impurity peak area of maximum, with contrast solution main constituent peak area ratio.With reference to chemicals impurity research guideline and " in two ones of the Chinese Pharmacopoeia versions in 2005 with the quality standard of veriety, the limit of this product is decided to be: the total impurities amount must not cross 2.0%, and single impurity level must not cross 0.5%.
Assay:
With reference to " with the quality standard of veriety, adopting the high effective liquid chromatography for measuring sample size in two ones of the Chinese Pharmacopoeia versions in 2005.Entecavir should be 90.0～110.0% of labelled amount.
Testing result sees Table lattice:
Table 1: Entecavir embodiment sample detection is table as a result
Entecavir of the present invention includes injection, sterile powder injection, and hepatitis B virus is had good inhibition effect, good stability.
The specific embodiment
Embodiment one
Entecavir 5mg
Sodium sulfite 0.2g
Water for injection adds to 1000mL
Embodiment two
Entecavir 0.1g
Propylene glycol 2mL
Sodium sulfite 0.2g
Water for injection adds to 1000mL
Embodiment three
Entecavir 1.0g
Propylene glycol 10mL
Sodium sulfite 0.4g
Water for injection adds to 1000mL
Embodiment four
Entecavir 2.5g
Propylene glycol 20ml
Sodium sulfite 0.5g
Water for injection adds to 1000mL
Above-mentioned Entecavir injection preparation technology: Entecavir is added in 60～80 ℃ of water, stirs, add cosolvent, Entecavir is all dissolved, be cooled to 40～50 ℃; Regulate pH4.0～9.0, add active carbon, stir 15min, leave standstill filtration, add antioxidant, add water for injection again to full dose, stir, fine straining is to qualified; Embedding, autoclaving promptly get entecavir injection.
Embodiment five
Entecavir 1.0g
Propylene glycol 10ml
Mannitol 100g
Water for injection adds to 1000mL
Above-mentioned Entecavir lyophilized injectable powder preparation method: Entecavir is added in 60～80 ℃ of water, adds propylene glycol, stir, Entecavir is all dissolved, add mannitol, stir, be cooled to 40～50 ℃; Add active carbon, stir 15min, filter while hot, add antioxidant, regulate pH4.0～9.0, fine straining, packing, lyophilization promptly gets the injection Entecavir.
Embodiment six
Entecavir 2.5g
Propylene glycol 20ml
Sodium chloride 9g
Glucose 45g
Water for injection adds to 1000mL
Above-mentioned Entecavir high-capacity injection preparation method: Entecavir is added in 60～80 ℃ of water, adds propylene glycol, stir, Entecavir is all dissolved, add sodium chloride, glucose, stir, be cooled to 40～50 ℃; Add active carbon, stir 15min, filter while hot, add antioxidant, regulate pH4.0～9.0, fine straining, packing promptly gets the Entecavir high-capacity injection.
The entecavir injection solution stability testing:
According to related content in 2005 editions two appendix of Chinese Pharmacopoeia " medicine stability test guideline ", respectively example 1, example 5 and 6 three batches of self-controls of example entecavir injection have been carried out study on the stability, with projects such as appearance character, content, related substances serves as to investigate index, the Entecavir injection is carried out quickening in 6 months to investigate and 12 months long term tests, the results are shown in following table:
Table 2: Entecavir injection accelerated test result (example 1)
Table 3: Entecavir injection long-term test results (example 1)
Table 4: injection Entecavir accelerated test result (example 5)
Table 5: the long-term accelerated test result of injection Entecavir (example 5)
Table 6: Entecavir high-capacity injection accelerated test result (example 6)
Table 7: Entecavir high-capacity injection long-term test results (example 6)
Claims (5)
1. entecavir injection comprises injection with small volume, high capacity sterile solution for injection, freeze dry sterile powder injection, it is characterized in that this medicine is to add additives by the active Entecavir 0.1-2.5mg of single dose to be prepared into; Additives comprise solvent for injection, pH regulator agent 0-10%, antioxidant 0-10%, solubilizing agent 0-60%, etc. open regulator 0-20%, filler 0.1-20%, filling bracket agent 0.1-20%, above-mentioned percentage ratio accounts for the percentage ratio of liquor capacity for this medicine gross mass.
2. entecavir injection according to claim 1, it is characterized in that described injection with small volume, be to add additives by active Entecavir to be prepared into, wherein active Entecavir solution concentration is 0.005-2.5mg/ml, pH regulator agent 0～10% in the additives, antioxidant 0～10%, solubilizing agent 0～60%, above-mentioned percentage ratio account for the percentage ratio of liquor capacity for this medicine gross mass.
3. entecavir injection according to claim 1, it is characterized in that described high capacity sterile solution for injection is to add additives by active Entecavir to be prepared from, wherein active Entecavir solution concentration is that 0.005-0.5mg/ml, pH regulator agent are about 0～10%, antioxidant 0～10%, etc. open about 0%～20%, the solubilizing agent 0～60% of regulator, above-mentioned percentage ratio accounts for the percentage ratio of liquor capacity for this medicine gross mass.
4. entecavir injection according to claim 1, it is characterized in that described freeze dry sterile powder injection is to add additives by active Entecavir to be prepared into solution, packing, lyophilization forms, before the packing in the solution: the active Entecavir concentration of principal agent is that 0.005-2.5mg/ml, pH regulator agent are about 0～10%, filler 0.1-20%, filling bracket agent 0.1%～20%, antioxidant 0～10%, and above-mentioned percentage ratio accounts for the percentage ratio of liquor capacity for this medicine gross mass.
5. entecavir injection according to claim 1 is characterized in that:
Described active Entecavir comprises: Entecavir and solvate thereof, hydrate, monocrystalline type, polymorphic, mixed crystal type, armorphous; The officinal salt that also comprises Entecavir, the pharmaceutically acceptable medicinal acid addition salt with the pharmacological action of Entecavir equivalence of having that refer to keep the biological effectiveness of parent compound and characteristic, the hydrochlorate that for example comprises Entecavir, mesylate, oxalates, acetate, lactate, gluconate, tartrate, citrate, fumarate, succinate, malate, maleate, benzoate, and the solvate of above-mentioned salt, hydrate, monocrystalline type, polymorphic, mixed crystal type, the biological salts substances of armorphous Entecavir derivant; The above-described existence form that all is Entecavir as active component;
The solvent of described injection is water for injection or non-water-soluble matchmaker, non-water-soluble matchmaker can be divided into oiliness solvent and the non-water-soluble matchmaker of water solublity, and the oiliness solvent comprises injection vegetable oil, ethyl oleate, triacetyl glycerine, ethyl acetate, ethyl carbonate, ethyl lactate, acetic acid butyl propionate, benzyl benzoate, Semen Myristicae isopropyl alcohol ester etc.; The non-water-soluble matchmaker of water solublity comprises alcohols, for example ethanol, glycerol, propylene glycol, 1,3 butylene glycol, Macrogol 200, Liquid Macrogol, PEG400, Polyethylene Glycol 1600, phenylpropanol etc.; Amide-type, for example dimethyl formamide, dimethyl acetylamide, just-(beta-hydroxyethyl) lactamide, N, N-diethyl lactamide, N, N-diethyl-2-picolinamide; The dioxolanes class, for example formal glycerine, 4-methylol-1,3-dioxolanes, 5-hydroxyl-1,3-dioxolanes, 2,2-dimethyl-1,3-dioxolanes-4-methanol etc. and sulfoxide class;
The additives of described injection have antioxidant, metal chelating agent, noble gas, solubilising cosolvent, growth of microorganism inhibitor, pH regulator agent, etc. open regulator, analgesic, filling bracket agent;
The antioxidant of described injection comprises sulfites antioxidant, as sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, sodium formaldehyde sulphoxylate, sodium dithionite; Thio-compounds is as thioglycerin, thiourea, 2 mercapto ethanol, dimercaptopropanol, BAL, 1-sulfo-sorbitol; Polyatomic phenol is as hydroquinone, para-aminophenol, oxine; Its acids of ammonia is as L-cysteine hydrochloride, L-methionine, L-lysine, L-propylhomoserin, L-arginine, L-leucine, L-isoleucine, L-tryptophan, L-glutathion; Other classes are as in ethylenediaminetetraacetic acid, disodium edta, succinic acid, citric acid, hydroquinone, malic acid, ascorbic acid, sodium ascorbate, inositol, alpha-tocopherol, α-tocopheryl acetate, xylitol, the D-xylose one or more;
Metal chelating agent in the described injection comprises dicarboxylic acid compounds such as disodiumedetate, citric acid, tartaric acid;
Noble gas in the described injection comprises nitrogen, argon, neon, krypton and carbon dioxide; Flocculating agent comprises benzyl alcohol, phenethanol;
Growth of microorganism inhibitor in the described injection comprises bromo geramine 0.01%, phemerol chloride 0.01%, benzyl alcohol 1.0%, chlorobutanol 0.5%, chlorocresol 0.1% to 0.25%, cresol 0.3%, methyl hydroxybenzoate 0.18%, propylparaben 0.02%, phenol 0.5%, nitric acid or phenylmercuric acetate 0.02%, thimerosal 0.01%, phenethanol 0.25% to 0.5%;
PH regulator agent in the described injection comprises mineral acid and organic acid, and wherein mineral acid has sulphuric acid, hydrochloric acid, phosphoric acid and phosphate buffer, acetate buffer according to Professional knowledge other mineral acids as can be known; Organic acid comprises acetic acid, lactic acid, methanesulfonic acid, citric acid, maleic acid and according to Professional knowledge other organic acid as can be known;
PH regulator agent in the described injection can also comprise all kinds of inorganic bases and organic base, wherein inorganic base comprises sodium hydroxide, potassium hydroxide and according to Professional knowledge other inorganic bases as can be known, organic base comprises triethanolamine and according to Professional knowledge other organic bases as can be known, preferred sodium hydroxide;
Regulator in the described injection comprises 5% glucose solution and 0.9% sodium chloride solution;
Filler in the described injection or filling bracket agent comprise one or more the mixture in lactose, sucrose, glucose, mannitol, sodium dihydrogen phosphate, sodium chloride, sodium hydrogen phosphate, cysteine, gelatin hydrolysate, glycine, sorbitol, calcium lactobionate., dextran, the polyvinylpyrrolidone;
Analgesic in the described injection comprises benzyl alcohol 1%, chlorobutanol 0.25% to 0.5%, procaine hydrochloride 0.5% to 2%, lignocaine 0.5% to 1.0%, urethane 6.25%.
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|---|---|---|---|
| CN200910220604A CN101716137A (en) | 2009-12-10 | 2009-12-10 | Entecavir injection |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013067769A1 (en) * | 2011-11-10 | 2013-05-16 | 陈小花 | Liquid composition of anti-hepatitis b virus |
| CN104490768A (en) * | 2014-12-01 | 2015-04-08 | 上海同仁药业有限公司 | Doramectin injection and preparation method thereof |
| KR20190043866A (en) * | 2017-10-19 | 2019-04-29 | 단국대학교 천안캠퍼스 산학협력단 | Stabilizing composition for aqueous suspension of entecavir fatty acid esters analogs |
| CN114224832A (en) * | 2022-02-11 | 2022-03-25 | 明度智云(浙江)科技有限公司 | Enzalutamide injection and preparation method and application thereof |
-
2009
- 2009-12-10 CN CN200910220604A patent/CN101716137A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013067769A1 (en) * | 2011-11-10 | 2013-05-16 | 陈小花 | Liquid composition of anti-hepatitis b virus |
| CN104490768A (en) * | 2014-12-01 | 2015-04-08 | 上海同仁药业有限公司 | Doramectin injection and preparation method thereof |
| KR20190043866A (en) * | 2017-10-19 | 2019-04-29 | 단국대학교 천안캠퍼스 산학협력단 | Stabilizing composition for aqueous suspension of entecavir fatty acid esters analogs |
| KR102197257B1 (en) | 2017-10-19 | 2020-12-31 | 단국대학교 천안캠퍼스 산학협력단 | Stabilizing composition for aqueous suspension of entecavir fatty acid esters analogs |
| CN114224832A (en) * | 2022-02-11 | 2022-03-25 | 明度智云(浙江)科技有限公司 | Enzalutamide injection and preparation method and application thereof |
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Open date: 20100602 |