CN115569113B - Valganciclovir hydrochloride oral solution - Google Patents
Valganciclovir hydrochloride oral solution Download PDFInfo
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- CN115569113B CN115569113B CN202211147621.3A CN202211147621A CN115569113B CN 115569113 B CN115569113 B CN 115569113B CN 202211147621 A CN202211147621 A CN 202211147621A CN 115569113 B CN115569113 B CN 115569113B
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- valganciclovir hydrochloride
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- oral solution
- hydrochloride oral
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- ZORWARFPXPVJLW-MTFPJWTKSA-N [2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]-3-hydroxypropyl] (2s)-2-amino-3-methylbutanoate;hydron;chloride Chemical compound Cl.N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 ZORWARFPXPVJLW-MTFPJWTKSA-N 0.000 title claims abstract description 134
- 229960004983 valganciclovir hydrochloride Drugs 0.000 title claims abstract description 133
- 229940100688 oral solution Drugs 0.000 title claims abstract description 88
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 79
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 56
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 56
- 239000003814 drug Substances 0.000 claims abstract description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 40
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 36
- 229930195725 Mannitol Natural products 0.000 claims abstract description 36
- 239000000594 mannitol Substances 0.000 claims abstract description 36
- 235000010355 mannitol Nutrition 0.000 claims abstract description 36
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims abstract description 29
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 28
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims abstract description 28
- 239000004376 Sucralose Substances 0.000 claims abstract description 28
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 28
- 235000011187 glycerol Nutrition 0.000 claims abstract description 28
- 235000010445 lecithin Nutrition 0.000 claims abstract description 28
- 239000000787 lecithin Substances 0.000 claims abstract description 28
- 229940067606 lecithin Drugs 0.000 claims abstract description 28
- 239000011780 sodium chloride Substances 0.000 claims abstract description 28
- 239000000600 sorbitol Substances 0.000 claims abstract description 28
- 235000010356 sorbitol Nutrition 0.000 claims abstract description 28
- 235000019408 sucralose Nutrition 0.000 claims abstract description 28
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims abstract description 28
- 235000002906 tartaric acid Nutrition 0.000 claims abstract description 28
- 239000011975 tartaric acid Substances 0.000 claims abstract description 28
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 26
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 26
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims abstract description 24
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims abstract description 24
- 229910001868 water Inorganic materials 0.000 claims abstract description 22
- 239000004289 sodium hydrogen sulphite Substances 0.000 claims abstract description 14
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims abstract description 11
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 11
- 235000002639 sodium chloride Nutrition 0.000 claims abstract description 10
- 229960004756 ethanol Drugs 0.000 claims abstract description 7
- 229960005150 glycerol Drugs 0.000 claims abstract description 7
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 7
- 208000030507 AIDS Diseases 0.000 claims description 6
- 241000701022 Cytomegalovirus Species 0.000 claims description 6
- 206010038910 Retinitis Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000003860 storage Methods 0.000 abstract description 6
- 239000007788 liquid Substances 0.000 description 42
- 238000003756 stirring Methods 0.000 description 31
- 230000000052 comparative effect Effects 0.000 description 21
- 239000008213 purified water Substances 0.000 description 18
- 239000011259 mixed solution Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 15
- 229920000139 polyethylene terephthalate Polymers 0.000 description 15
- 239000005020 polyethylene terephthalate Substances 0.000 description 15
- 239000012528 membrane Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 12
- 238000011835 investigation Methods 0.000 description 10
- 238000009472 formulation Methods 0.000 description 6
- -1 polyethylene terephthalate Polymers 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 5
- 238000005286 illumination Methods 0.000 description 4
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 4
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 4
- WPVFJKSGQUFQAP-GKAPJAKFSA-N Valcyte Chemical compound N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 WPVFJKSGQUFQAP-GKAPJAKFSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- 229960002149 valganciclovir Drugs 0.000 description 3
- 230000001133 acceleration Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A61P27/02—Ophthalmic agents
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A61P31/12—Antivirals
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- A61P31/22—Antivirals for DNA viruses for herpes viruses
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to a valganciclovir hydrochloride oral solution. The valganciclovir hydrochloride oral solution comprises valganciclovir hydrochloride, ethanol, glycerol, polyethylene glycol 400, sucralose, sorbitol, mannitol, lecithin, polyvinyl alcohol, tartaric acid, sodium bisulphite, sodium chloride and water. The valganciclovir hydrochloride oral solution disclosed by the invention has excellent stability, so that the valganciclovir hydrochloride oral solution has excellent storage and transportation stability, the quality of a medicine is ensured, and the medication safety of the valganciclovir hydrochloride oral solution is further effectively ensured.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a valganciclovir hydrochloride oral solution.
Background
Valganciclovir hydrochloride (CAS number 175865-59-5) is useful for treating patients with acquired immunodeficiency syndrome (AIDS) complicated with Cytomegalovirus (CMV) retinitis, and for preventing CMV infection in high risk solid organ transplant patients, and has the following structural formula:
the existing valganciclovir hydrochloride dosage forms are mainly solid preparations such as tablets, however, the solid preparations such as tablets relate to dissolution of medicines, have slower effect, are inconvenient for patients with difficult swallowing, and lead to poor compliance of the patients. The oral liquid preparation can be prepared by simple batch filling, is suitable for administration by patients with difficult swallowing, and has strong patient compliance. However, valganciclovir hydrochloride has the problem of poor stability in water and is easily influenced by various factors such as illumination, heat and the like, so that the valganciclovir hydrochloride oral solution has poor stability, and is unfavorable for storage and transportation stability of the valganciclovir hydrochloride oral solution, thereby adversely affecting the quality of the valganciclovir hydrochloride oral solution and further limiting the application of the valganciclovir hydrochloride oral solution.
Accordingly, there is a need in the art to develop an oral solution of valganciclovir hydrochloride having excellent stability.
Disclosure of Invention
The invention aims to provide valganciclovir hydrochloride oral solution with excellent stability.
In a first aspect of the present invention, there is provided an oral solution of valganciclovir hydrochloride comprising valganciclovir hydrochloride, ethanol, glycerol, polyethylene glycol 400, sucralose, sorbitol, mannitol, lecithin, polyvinyl alcohol, tartaric acid, sodium bisulphite, sodium chloride and water.
Preferably, the valganciclovir hydrochloride is 1 to 10 parts by weight, preferably 3 to 7 parts by weight, more preferably 4 to 6 parts by weight, most preferably 5.0 parts by weight.
Preferably, the valganciclovir hydrochloride is present in an amount of 1-10g/100ml, preferably 3-7g/100ml, more preferably 4-6g/100ml, most preferably 5.0g/100ml.
Preferably, the ethanol is 20-40 parts by weight, preferably 25-35 parts by weight, more preferably 28-32 parts by weight, most preferably 30 parts by weight.
Preferably, the ethanol content is 20-40g/100ml, preferably 25-35g/100ml, more preferably 28-32g/100ml, most preferably 30g/100ml.
Preferably, the glycerol is 1-10 parts by weight, preferably 4-8 parts by weight, more preferably 5-7 parts by weight, most preferably 6 parts by weight.
Preferably, the glycerol is present in an amount of 1-10g/100ml, preferably 4-8g/100ml, more preferably 5-7g/100ml, most preferably 6g/100ml.
Preferably, the polyethylene glycol 400 is 1 to 10 parts by weight, preferably 3 to 7 parts by weight, more preferably 4 to 6 parts by weight, and most preferably 5.0 parts by weight.
Preferably, the polyethylene glycol 400 is present in an amount of 1-10g/100ml, preferably 3-7g/100ml, more preferably 4-6g/100ml, most preferably 5.0g/100ml.
Preferably, the sucralose is 0.02 to 0.15 parts by weight, preferably 0.06 to 0.10 parts by weight, more preferably 0.07 to 0.09 parts by weight, and most preferably 0.08 parts by weight.
Preferably, the sucralose is present in an amount of 0.02 to 0.15g/100ml, preferably 0.06 to 0.10g/100ml, more preferably 0.07 to 0.09g/100ml, most preferably 0.08g/100ml.
Preferably, the sorbitol is 1-3 parts by weight, preferably 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, most preferably 2.0 parts by weight.
Preferably, the sorbitol is present in an amount of 1-3g/100ml, preferably 1.5-2.5g/100ml, more preferably 1.8-2.2g/100ml, most preferably 2.0g/100ml.
Preferably, the mannitol is 0.5 to 3 parts by weight, preferably 1 to 2 parts by weight, more preferably 1.3 to 1.7 parts by weight, most preferably 1.5 parts by weight.
Preferably, the mannitol is present in an amount of 0.5-3g/100ml, preferably 1-2g/100ml, more preferably 1.3-1.7g/100ml, most preferably 1.5g/100ml.
Preferably, the lecithin is present in an amount of 0.1 to 0.5 parts by weight, preferably 0.2 to 0.3 parts by weight, more preferably 0.23 to 0.27 parts by weight, and most preferably 0.25 parts by weight.
Preferably, the lecithin is present in an amount of 0.1-0.5g/100ml, preferably 0.2-0.3g/100ml, more preferably 0.23-0.27g/100ml, most preferably 0.25g/100ml.
Preferably, the polyvinyl alcohol is 0.2 to 3 parts by weight, preferably 0.5 to 1.5 parts by weight, more preferably 0.8 to 1.2 parts by weight, and most preferably 1.0 part by weight.
Preferably, the polyvinyl alcohol is present in an amount of 0.2 to 3g/100ml, preferably 0.5 to 1.5g/100ml, more preferably 0.8 to 1.2g/100ml, most preferably 1.0g/100ml.
Preferably, the tartaric acid is 3 to 5 parts by weight, preferably 3.5 to 4.5 parts by weight, more preferably 3.8 to 4.2 parts by weight, and most preferably 4.0 parts by weight.
Preferably, the tartaric acid is present in an amount of 3-5g/100ml, preferably 3.5-4.5g/100ml, more preferably 3.8-4.2g/100ml, most preferably 4.0g/100ml.
Preferably, the sodium bisulfite is in the range of 0.02 to 0.2 parts by weight, preferably 0.02 to 0.1 parts by weight, more preferably 0.04 to 0.08 parts by weight, and most preferably 0.06 parts by weight.
Preferably, the sodium bisulphite is present in an amount of 0.02 to 0.2g/100ml, preferably 0.02 to 0.1g/100ml, more preferably 0.04 to 0.08g/100ml, most preferably 0.06g/100ml.
Preferably, the sodium chloride is 0.05 to 1.0 parts by weight, preferably 0.1 to 0.5 parts by weight, more preferably 0.1 to 0.3 parts by weight, most preferably 0.2 parts by weight.
Preferably, the sodium chloride is present in an amount of 0.05-1.0g/100ml, preferably 0.1-0.5g/100ml, more preferably 0.1-0.3g/100ml, most preferably 0.2g/100ml.
Preferably, the water is 50 to 70 parts by weight, preferably 55 to 65 parts by weight, more preferably 57 to 62 parts by weight, most preferably 58 to 60 parts by weight.
Preferably, the water comprises purified water.
Preferably, the parts by weight are in g.
Preferably, the valganciclovir hydrochloride oral solution comprises:
preferably, the valganciclovir hydrochloride oral solution comprises:
| component (A) | Dosage of |
| Valganciclovir hydrochloride | 4-6 parts by weight |
| Ethanol | 28-32 parts by weight |
| Glycerol | 5-7 parts by weight |
| Polyethylene glycol 400 | 4-6 parts by weight |
| Sucralose | 0.06-0.10 part by weight |
| Sorbitol | 1.5 to 2.5 parts by weight |
| Mannitol (mannitol) | 1-2 parts by weight |
| Lecithin | 0.2 to 0.3 part by weight |
| Polyvinyl alcohol | 0.8-1.2 parts by weight |
| Tartaric acid | 3-5 parts by weight |
| Sodium bisulfite | 0.04 to 0.08 part by weight |
| Sodium chloride | 0.1 to 0.3 weight portions; and |
| water and its preparation method | 57-62 parts by weight. |
Preferably, the valganciclovir hydrochloride oral solution comprises:
| component (A) | Dosage of |
| Valganciclovir hydrochloride | 5.0g |
| Ethanol | 30g |
| Glycerol | 6.0g |
| Polyethylene glycol 400 | 5.0g |
| Sucralose | 0.08g |
| Sorbitol | 2.0g |
| Mannitol (mannitol) | 1.5g |
| Lecithin | 0.25g |
| Polyvinyl alcohol | 1.0g |
| Tartaric acid | 4.0g |
| Sodium bisulfite | 0.06g |
| Sodium chloride | 0.2g |
| Purified water | To 100ml. |
In a second aspect of the present invention, there is provided a process for preparing an oral solution of valganciclovir hydrochloride according to the first aspect of the present invention, said process comprising the steps of:
and mixing the valganciclovir hydrochloride, ethanol, glycerol, polyethylene glycol 400, sucralose, sorbitol, mannitol, lecithin, polyvinyl alcohol, tartaric acid, sodium bisulphite, sodium chloride and water to obtain the valganciclovir hydrochloride oral solution.
Preferably, the method comprises:
(1) Mixing 75-85% of water with ethanol, glycerol and polyethylene glycol 400, dissolving, adding valganciclovir hydrochloride into the mixed solution, and stirring, mixing and dissolving to obtain liquid medicine 1;
(2) Adding lecithin and polyvinyl alcohol into the liquid medicine 1, stirring, mixing and dissolving, adding sucralose, sorbitol, mannitol, tartaric acid, sodium bisulphite and sodium chloride into the mixed solution, stirring, mixing and dissolving to obtain liquid medicine 2;
(3) Adding water into the liquid medicine 2 to fix the volume to the dosage volume, stirring and mixing uniformly, and filtering to obtain the valganciclovir hydrochloride oral solution.
Preferably, the method comprises:
(1) Mixing 75-85% of water with ethanol, glycerol and polyethylene glycol 400 at 40-50deg.C, adding valganciclovir hydrochloride into the mixture, and stirring at 40-50deg.C to obtain liquid medicine 1;
(2) Adding lecithin and polyvinyl alcohol into the liquid medicine 1, stirring, mixing and dissolving at 40-50 ℃, adding sucralose, sorbitol, mannitol, tartaric acid, sodium bisulphite and sodium chloride into the mixed solution, stirring, mixing and dissolving at 40-50 ℃ to obtain liquid medicine 2.
(3) Adding water into the liquid medicine 2 to fix the volume to the dosage volume, stirring and mixing uniformly, and filtering to obtain the valganciclovir hydrochloride oral solution.
Preferably, the filtration is performed by a microporous filter membrane.
Preferably, the filtration comprises filtration through a 0.45 μm and a 0.22 μm microporous filter membrane in sequence.
In a third aspect of the present invention, there is provided a kit comprising a transparent container and an oral solution of valganciclovir hydrochloride according to the first aspect of the present invention.
Preferably, the valganciclovir hydrochloride oral solution according to the first aspect of the invention is packaged in the transparent container.
Preferably, the transparent container comprises a transparent plastic container or a transparent glass container.
Preferably, the transparent container comprises a transparent PET bottle.
In a fourth aspect of the present invention there is provided the use of an oral solution of valganciclovir hydrochloride according to the first aspect of the present invention for the preparation of a medicament for the treatment of acquired immunodeficiency syndrome (AIDS) combined with Cytomegalovirus (CMV) retinitis.
It is understood that within the scope of the present invention, the above-described technical features of the present invention and technical features specifically described below (e.g., in the examples) may be combined with each other to constitute new or preferred technical solutions.
Detailed Description
The invention provides a valganciclovir hydrochloride oral solution, which comprises valganciclovir, ethanol, glycerol, polyethylene glycol 400, sucralose, sorbitol, mannitol, lecithin, polyvinyl alcohol, tartaric acid, sodium bisulfate, sodium chloride and water. The valganciclovir hydrochloride oral solution disclosed by the invention has excellent stability, so that the valganciclovir hydrochloride oral solution has excellent storage and transportation stability, the quality of a medicine is ensured, and the medication safety of the valganciclovir hydrochloride oral solution is further effectively ensured.
Terminology
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
As used herein, the terms "comprising," "including," and "containing" are used interchangeably, and include not only closed-form definitions, but also semi-closed-form and open-form definitions. In other words, the term includes "consisting of … …", "consisting essentially of … …".
As used herein, the term "PET" refers to polyethylene terephthalate, english name Poly (ethylene Terephthalate).
As used herein, the term "polyethylene glycol 400" is abbreviated PEG-400, and the english name Poly (ethylene glycol) 400.
As used herein, the english language of the term "polyvinyl alcohol" is Polyvinyl Alcohol, CAS number: 9002-89-5.
As used herein, the english language of the term "Lecithin" is Lecithin, CAS no: 8002-43-5.
As used herein, the term "parts by weight" may be any fixed weight in milligrams, grams, or kilograms (e.g., 1mg, 1g, or 1kg, etc.). For example, a composition comprising 1 part by weight of component a and 9 parts by weight of component b may be a composition comprising 1 gram of component a+9 gram of component b, or 10 grams of component a+90 gram of component b, etc. In the valganciclovir hydrochloride oral solution, the percentage content of a certain component = (the sum of parts by weight of the component/parts by weight of all components) ×100%, and therefore, in the composition composed of 1 part by weight of component a and 9 parts by weight of component b, the content of component a is 10%, and the content of component b is 90%.
Oral solution
The valganciclovir hydrochloride oral solution provided by the invention has excellent stability.
The valganciclovir hydrochloride oral solution comprises valganciclovir hydrochloride, ethanol, glycerol, polyethylene glycol 400, sucralose, sorbitol, mannitol, lecithin, polyvinyl alcohol, tartaric acid, sodium bisulphite, sodium chloride and water.
In a preferred embodiment of the present invention, the valganciclovir hydrochloride is 1 to 10 parts by weight, preferably 3 to 7 parts by weight, more preferably 4 to 6 parts by weight, most preferably 5.0 parts by weight.
Preferably, the valganciclovir hydrochloride is present in an amount of 1-10g/100ml, preferably 3-7g/100ml, more preferably 4-6g/100ml, most preferably 5.0g/100ml.
In a preferred embodiment of the present invention, the ethanol is 20 to 40 parts by weight, preferably 25 to 35 parts by weight, more preferably 28 to 32 parts by weight, most preferably 30 parts by weight.
Preferably, the ethanol content is 20-40g/100ml, preferably 25-35g/100ml, more preferably 28-32g/100ml, most preferably 30g/100ml.
In a preferred embodiment of the invention, the glycerol is 1-10 parts by weight, preferably 4-8 parts by weight, more preferably 5-7 parts by weight, most preferably 6 parts by weight.
Preferably, the glycerol is present in an amount of 1-10g/100ml, preferably 4-8g/100ml, more preferably 5-7g/100ml, most preferably 6g/100ml.
In a preferred embodiment of the present invention, the polyethylene glycol 400 is 1 to 10 parts by weight, preferably 3 to 7 parts by weight, more preferably 4 to 6 parts by weight, and most preferably 5.0 parts by weight.
Preferably, the polyethylene glycol 400 is present in an amount of 1-10g/100ml, preferably 3-7g/100ml, more preferably 4-6g/100ml, most preferably 5.0g/100ml.
In a preferred embodiment of the present invention, the sucralose is 0.02 to 0.15 parts by weight, preferably 0.06 to 0.10 parts by weight, more preferably 0.07 to 0.09 parts by weight, and most preferably 0.08 parts by weight.
Preferably, the sucralose is present in an amount of 0.02 to 0.15g/100ml, preferably 0.06 to 0.10g/100ml, more preferably 0.07 to 0.09g/100ml, most preferably 0.08g/100ml.
In a preferred embodiment of the invention, the sorbitol is 1-3 parts by weight, preferably 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, most preferably 2.0 parts by weight.
Preferably, the sorbitol is present in an amount of 1-3g/100ml, preferably 1.5-2.5g/100ml, more preferably 1.8-2.2g/100ml, most preferably 2.0g/100ml.
In a preferred embodiment of the invention, the mannitol is 0.5-3 parts by weight, preferably 1-2 parts by weight, more preferably 1.3-1.7 parts by weight, most preferably 1.5 parts by weight.
Preferably, the mannitol is present in an amount of 0.5-3g/100ml, preferably 1-2g/100ml, more preferably 1.3-1.7g/100ml, most preferably 1.5g/100ml.
In a preferred embodiment of the invention, the lecithin is present in an amount of 0.1 to 0.5 parts by weight, preferably 0.2 to 0.3 parts by weight, more preferably 0.23 to 0.27 parts by weight, and most preferably 0.25 parts by weight.
Preferably, the lecithin is present in an amount of 0.1-0.5g/100ml, preferably 0.2-0.3g/100ml, more preferably 0.23-0.27g/100ml, most preferably 0.25g/100ml.
In a preferred embodiment of the present invention, the polyvinyl alcohol is 0.2 to 3 parts by weight, preferably 0.5 to 1.5 parts by weight, more preferably 0.8 to 1.2 parts by weight, most preferably 1.0 part by weight.
Preferably, the polyvinyl alcohol is present in an amount of 0.2 to 3g/100ml, preferably 0.5 to 1.5g/100ml, more preferably 0.8 to 1.2g/100ml, most preferably 1.0g/100ml.
In a preferred embodiment of the present invention, the tartaric acid is 3 to 5 parts by weight, preferably 3.5 to 4.5 parts by weight, more preferably 3.8 to 4.2 parts by weight, and most preferably 4.0 parts by weight.
Preferably, the tartaric acid is present in an amount of 3-5g/100ml, preferably 3.5-4.5g/100ml, more preferably 3.8-4.2g/100ml, most preferably 4.0g/100ml.
In a preferred embodiment of the present invention, the sodium bisulfite is in the range of 0.02 to 0.2 parts by weight, preferably 0.02 to 0.1 parts by weight, more preferably 0.04 to 0.08 parts by weight, and most preferably 0.06 parts by weight.
Preferably, the sodium bisulphite is present in an amount of 0.02 to 0.2g/100ml, preferably 0.02 to 0.1g/100ml, more preferably 0.04 to 0.08g/100ml, most preferably 0.06g/100ml.
In a preferred embodiment of the invention, the sodium chloride is present in an amount of 0.05 to 1.0 parts by weight, preferably 0.1 to 0.5 parts by weight, more preferably 0.1 to 0.3 parts by weight, most preferably 0.2 parts by weight.
Preferably, the sodium chloride is present in an amount of 0.05-1.0g/100ml, preferably 0.1-0.5g/100ml, more preferably 0.1-0.3g/100ml, most preferably 0.2g/100ml.
In a preferred embodiment of the invention, the water is 50-70 parts by weight, preferably 55-65 parts by weight, more preferably 57-62 parts by weight, most preferably 58-60 parts by weight.
Preferably, the water comprises purified water.
Preferably, the parts by weight are in g.
Typically, the valganciclovir hydrochloride oral solution comprises:
typically, the valganciclovir hydrochloride oral solution comprises:
| component (A) | Dosage of |
| Valganciclovir hydrochloride | 4-6 parts by weight |
| Ethanol | 28-32 parts by weight |
| Glycerol | 5-7 parts by weight |
| Polyethylene glycol 400 | 4-6 parts by weight |
| Sucralose | 0.06-0.10 part by weight |
| Sorbitol | 1.5 to 2.5 parts by weight |
| Mannitol (mannitol) | 1-2 parts by weight |
| Lecithin | 0.2 to 0.3 part by weight |
| Polyvinyl alcohol | 0.8-1.2 parts by weight |
| Tartaric acid | 3-5 parts by weight |
| Sodium bisulfite | 0.04 to 0.08 part by weight |
| Sodium chloride | 0.1 to 0.3 weight portions; and |
| water and its preparation method | 57-62 parts by weight. |
Typically, the valganciclovir hydrochloride oral solution comprises:
Method
the invention provides a preparation method of valganciclovir hydrochloride oral solution, which comprises the following steps:
and mixing the valganciclovir hydrochloride, ethanol, glycerol, polyethylene glycol 400, sucralose, sorbitol, mannitol, lecithin, polyvinyl alcohol, tartaric acid, sodium bisulphite, sodium chloride and water to obtain the valganciclovir hydrochloride oral solution.
In a preferred embodiment of the invention, the method comprises:
(1) Mixing 75-85% of water with ethanol, glycerol and polyethylene glycol 400, dissolving, adding valganciclovir hydrochloride into the mixed solution, and stirring, mixing and dissolving to obtain liquid medicine 1;
(2) Adding lecithin and polyvinyl alcohol into the liquid medicine 1, stirring, mixing and dissolving, adding sucralose, sorbitol, mannitol, tartaric acid, sodium bisulphite and sodium chloride into the mixed solution, stirring, mixing and dissolving to obtain liquid medicine 2;
(3) Adding water into the liquid medicine 2 to fix the volume to the dosage volume, stirring and mixing uniformly, and filtering to obtain the valganciclovir hydrochloride oral solution.
Representatively, the method includes:
(1) Mixing 75-85% of water with ethanol, glycerol and polyethylene glycol 400 at 40-50deg.C, adding valganciclovir hydrochloride into the mixture, and stirring at 40-50deg.C to obtain liquid medicine 1;
(2) Adding lecithin and polyvinyl alcohol into the liquid medicine 1, stirring, mixing and dissolving at 40-50 ℃, adding sucralose, sorbitol, mannitol, tartaric acid, sodium bisulphite and sodium chloride into the mixed solution, stirring, mixing and dissolving at 40-50 ℃ to obtain liquid medicine 2.
(3) Adding water into the liquid medicine 2 to fix the volume to the dosage volume, stirring and mixing uniformly, and filtering to obtain the valganciclovir hydrochloride oral solution.
Preferably, the filtration is performed by a microporous filter membrane.
Preferably, the filtration comprises filtration through a 0.45 μm and a 0.22 μm microporous filter membrane in sequence.
Medicine box
The invention also provides a medicine box, which comprises a transparent container and the valganciclovir hydrochloride oral solution.
In a preferred embodiment of the present invention, the valganciclovir hydrochloride oral solution of the present invention is packaged in the transparent container.
The transparent container according to the present invention may comprise a transparent plastic container or a transparent glass container. For example, the transparent container includes a transparent PET bottle.
The main excellent technical effects of the invention include:
1. the valganciclovir hydrochloride oral solution has excellent stability, so that the valganciclovir hydrochloride oral solution has excellent storage and transportation stability, ensures the quality of medicines, and further effectively ensures the medication safety of the valganciclovir hydrochloride oral solution.
2. The valganciclovir hydrochloride oral solution developed by the invention has high safety and strong oral compliance of patients.
The invention will be further illustrated with reference to specific examples. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. The experimental procedure, in which specific conditions are not noted in the examples below, is generally followed by conventional conditions.
EXAMPLE 1 valganciclovir hydrochloride oral solution
The formulation of valganciclovir hydrochloride oral solution of this example 1 is shown in table 1:
TABLE 1 prescription composition of valganciclovir hydrochloride oral solution (specification: 5g/100 ml)
| Component (A) | Dosage of |
| Valganciclovir hydrochloride | 5.0g |
| Ethanol | 30g |
| Glycerol | 6.0g |
| Polyethylene glycol 400 | 5.0g |
| Sucralose | 0.08g |
| Sorbitol | 2.0g |
| Mannitol (mannitol) | 1.5g |
| Lecithin | 0.25g |
| Polyvinyl alcohol | 1.0g |
| Tartaric acid | 4.0g |
| Sodium bisulfite | 0.06g |
| Sodium chloride | 0.2g |
| Purified water | To 100ml |
The preparation method of valganciclovir hydrochloride oral solution of this example 1 is as follows:
(1) After 80% of the purified water with the prescription amount, ethanol with the prescription amount, glycerin with the prescription amount and polyethylene glycol 400 with the prescription amount are stirred, mixed and dissolved at 45 ℃, valganciclovir hydrochloride with the prescription amount is added into the mixed solution, and the mixed solution is stirred, mixed and dissolved at 45 ℃ to obtain the liquid medicine 1.
(2) Adding a prescribed amount of lecithin and a prescribed amount of polyvinyl alcohol into the liquid medicine 1, stirring, mixing and dissolving at 45 ℃, adding a prescribed amount of sucralose, a prescribed amount of sorbitol, a prescribed amount of mannitol, a prescribed amount of tartaric acid, a prescribed amount of sodium bisulfate and a prescribed amount of sodium chloride into the mixed liquid, stirring, mixing and dissolving at 45 ℃, and obtaining liquid medicine 2.
(3) Adding boiled and cooled purified water into the liquid medicine 2 to a fixed volume to prepare a medicine, stirring and mixing uniformly, filtering sequentially through a microporous filter membrane with the size of 0.45 mu m and a microporous filter membrane with the size of 0.22 mu m to obtain valganciclovir hydrochloride oral solution, and packaging the valganciclovir hydrochloride oral solution into transparent PET (polyethylene terephthalate) bottles, wherein the specification of valganciclovir hydrochloride in each bottle is 5g/100ml.
Comparative example 1 valganciclovir hydrochloride oral solution
The formulation of valganciclovir hydrochloride oral solution of this comparative example 1 is shown in table 2:
TABLE 2 prescription composition of valganciclovir hydrochloride oral solution (specification: 5g/100 ml)
| Component (A) | Dosage of |
| Valganciclovir hydrochloride | 5.0g |
| Ethanol | 30g |
| Glycerol | 6.0g |
| Polyethylene glycol 400 | 5.0g |
| Sucralose | 0.08g |
| Sorbitol | 4.0g |
| Mannitol (mannitol) | 1.5g |
| Lecithin | 0.25g |
| Polyvinyl alcohol | 1.0g |
| Tartaric acid | 2.0g |
| Sodium bisulfite | 0.06g |
| Sodium chloride | 0.2g |
| Purified water | To 100ml |
The preparation method of valganciclovir hydrochloride oral solution of the comparative example 1 is as follows:
(1) After 80% of the purified water with the prescription amount, ethanol with the prescription amount, glycerin with the prescription amount and polyethylene glycol 400 with the prescription amount are stirred, mixed and dissolved at 45 ℃, valganciclovir hydrochloride with the prescription amount is added into the mixed solution, and the mixed solution is stirred, mixed and dissolved at 45 ℃ to obtain the liquid medicine 1.
(2) Adding a prescribed amount of lecithin and a prescribed amount of polyvinyl alcohol into the liquid medicine 1, stirring, mixing and dissolving at 45 ℃, adding a prescribed amount of sucralose, a prescribed amount of sorbitol, a prescribed amount of mannitol, a prescribed amount of tartaric acid, a prescribed amount of sodium bisulfate and a prescribed amount of sodium chloride into the mixed liquid, stirring, mixing and dissolving at 45 ℃, and obtaining liquid medicine 2.
(3) Adding boiled and cooled purified water into the liquid medicine 2 to a fixed volume to prepare a medicine, stirring and mixing uniformly, filtering sequentially through a microporous filter membrane with the size of 0.45 mu m and a microporous filter membrane with the size of 0.22 mu m to obtain valganciclovir hydrochloride oral solution, and packaging the valganciclovir hydrochloride oral solution into transparent PET (polyethylene terephthalate) bottles, wherein the specification of valganciclovir hydrochloride in each bottle is 5g/100ml.
Comparative example 2 valganciclovir hydrochloride oral solution
The formulation of valganciclovir hydrochloride oral solution of this comparative example 2 is shown in table 3:
TABLE 3 prescription composition of valganciclovir hydrochloride oral solution (specification: 5g/100 ml)
| Component (A) | Dosage of |
| Valganciclovir hydrochloride | 5.0g |
| Ethanol | 30g |
| Glycerol | 6.0g |
| Polyethylene glycol 400 | 5.0g |
| Sucralose | 0.08g |
| Sorbitol | 2.0g |
| Mannitol (mannitol) | 1.5g |
| Polyvinyl alcohol | 1.0g |
| Tartaric acid | 4.0g |
| Sodium bisulfite | 0.06g |
| Sodium chloride | 0.2g |
| Purified water | To 100ml |
The preparation method of valganciclovir hydrochloride oral solution of the comparative example 2 is as follows:
(1) After 80% of the purified water with the prescription amount, ethanol with the prescription amount, glycerin with the prescription amount and polyethylene glycol 400 with the prescription amount are stirred, mixed and dissolved at 45 ℃, valganciclovir hydrochloride with the prescription amount is added into the mixed solution, and the mixed solution is stirred, mixed and dissolved at 45 ℃ to obtain the liquid medicine 1.
(2) Adding a prescribed amount of polyvinyl alcohol into the liquid medicine 1, stirring, mixing and dissolving at 45 ℃, adding a prescribed amount of sucralose, a prescribed amount of sorbitol, a prescribed amount of mannitol, a prescribed amount of tartaric acid, a prescribed amount of sodium bisulfate and a prescribed amount of sodium chloride into the mixed liquid, stirring, mixing and dissolving at 45 ℃, and obtaining the liquid medicine 2.
(3) Adding boiled and cooled purified water into the liquid medicine 2 to a fixed volume to prepare a medicine, stirring and mixing uniformly, filtering sequentially through a microporous filter membrane with the size of 0.45 mu m and a microporous filter membrane with the size of 0.22 mu m to obtain valganciclovir hydrochloride oral solution, and packaging the valganciclovir hydrochloride oral solution into transparent PET (polyethylene terephthalate) bottles, wherein the specification of valganciclovir hydrochloride in each bottle is 5g/100ml.
Comparative example 3 valganciclovir hydrochloride oral solution
The formulation of valganciclovir hydrochloride oral solution of this comparative example 3 is shown in table 4:
TABLE 4 prescription composition of valganciclovir hydrochloride oral solution (specification: 5g/100 ml)
| Component (A) | Dosage of |
| Valganciclovir hydrochloride | 5.0g |
| Ethanol | 30g |
| Glycerol | 6.0g |
| Polyethylene glycol 400 | 5.0g |
| Sucralose | 0.08g |
| Sorbitol | 2.0g |
| Mannitol (mannitol) | 1.5g |
| Lecithin | 0.25g |
| Tartaric acid | 4.0g |
| Sodium bisulfite | 0.06g |
| Sodium chloride | 0.2g |
| Purified water | To 100ml |
The preparation method of valganciclovir hydrochloride oral solution of the comparative example 3 is as follows:
(1) After 80% of the purified water with the prescription amount, ethanol with the prescription amount, glycerin with the prescription amount and polyethylene glycol 400 with the prescription amount are stirred, mixed and dissolved at 45 ℃, valganciclovir hydrochloride with the prescription amount is added into the mixed solution, and the mixed solution is stirred, mixed and dissolved at 45 ℃ to obtain the liquid medicine 1.
(2) Adding a prescribed amount of lecithin into the liquid medicine 1, stirring, mixing and dissolving at 45 ℃, adding a prescribed amount of sucralose, a prescribed amount of sorbitol, a prescribed amount of mannitol, a prescribed amount of tartaric acid, a prescribed amount of sodium bisulphite and a prescribed amount of sodium chloride into the mixed liquid, stirring, mixing and dissolving at 45 ℃, and obtaining liquid medicine 2.
(3) Adding boiled and cooled purified water into the liquid medicine 2 to a fixed volume to prepare a medicine, stirring and mixing uniformly, filtering sequentially through a microporous filter membrane with the size of 0.45 mu m and a microporous filter membrane with the size of 0.22 mu m to obtain valganciclovir hydrochloride oral solution, and packaging the valganciclovir hydrochloride oral solution into transparent PET (polyethylene terephthalate) bottles, wherein the specification of valganciclovir hydrochloride in each bottle is 5g/100ml.
Comparative example 4 valganciclovir hydrochloride oral solution
The formulation of valganciclovir hydrochloride oral solution of this comparative example 4 is shown in table 5:
TABLE 5 prescription composition of valganciclovir hydrochloride oral solution (specification: 5g/100 ml)
| Component (A) | Dosage of |
| Valganciclovir hydrochloride | 5.0g |
| Ethanol | 30g |
| Glycerol | 6.0g |
| Polyethylene glycol 400 | 5.0g |
| Sucralose | 0.08g |
| Sorbitol | 0.5g |
| Mannitol (mannitol) | 1.5g |
| Lecithin | 0.25g |
| Tartaric acid | 4.0g |
| Sodium bisulfite | 0.06g |
| Sodium chloride | 0.2g |
| Purified water | To 100ml |
The preparation method of valganciclovir hydrochloride oral solution of the comparative example 4 is as follows:
(1) After 80% of the purified water with the prescription amount, ethanol with the prescription amount, glycerin with the prescription amount and polyethylene glycol 400 with the prescription amount are stirred, mixed and dissolved at 45 ℃, valganciclovir hydrochloride with the prescription amount is added into the mixed solution, and the mixed solution is stirred, mixed and dissolved at 45 ℃ to obtain the liquid medicine 1.
(2) Adding a prescribed amount of lecithin into the liquid medicine 1, stirring, mixing and dissolving at 45 ℃, adding a prescribed amount of sucralose, a prescribed amount of sorbitol, a prescribed amount of mannitol, a prescribed amount of tartaric acid, a prescribed amount of sodium bisulphite and a prescribed amount of sodium chloride into the mixed liquid, stirring, mixing and dissolving at 45 ℃, and obtaining liquid medicine 2.
(3) Adding boiled and cooled purified water into the liquid medicine 2 to a fixed volume to prepare a medicine, stirring and mixing uniformly, filtering sequentially through a microporous filter membrane with the size of 0.45 mu m and a microporous filter membrane with the size of 0.22 mu m to obtain valganciclovir hydrochloride oral solution, and packaging the valganciclovir hydrochloride oral solution into transparent PET (polyethylene terephthalate) bottles, wherein the specification of valganciclovir hydrochloride in each bottle is 5g/100ml.
Stability of valganciclovir hydrochloride oral solutions prepared in example 1 and comparative examples 1 to 4 were examined
1. Stability investigation of illumination factor
The valganciclovir hydrochloride oral solutions prepared in example 1 and comparative examples 1 to 4 were placed under light conditions (4500 lx,25 ℃) for 0 days, 10 days and 30 days, and the light stability of the valganciclovir hydrochloride oral solutions prepared in example 1 and comparative examples 1 to 4 was examined according to the guidelines of the stability test of the chinese pharmacopoeia preparations.
Light factor stability investigation index: valganciclovir content (%) and related substances content (%) of valganciclovir hydrochloride oral solutions at different investigation time points under the illumination condition were determined by high performance liquid chromatography.
The results of the light factor investigation of valganciclovir hydrochloride oral solutions prepared in example 1 and comparative examples 1-4 at different investigation time points are shown in table 6:
TABLE 6 investigation of the stability of the oral solutions of valganciclovir hydrochloride prepared in example 1 and comparative examples 1-4 with respect to the light factor (4500 lx,25 ℃)
From Table 6, the valganciclovir hydrochloride oral solution prepared in example 1 has excellent light stability and strong light stability, and can be simply packaged in a transparent container for storage and transportation.
2. Accelerated stability investigation
The valganciclovir hydrochloride oral solutions prepared in example 1 and comparative examples 1 to 4 were placed at a temperature of 40±2 ℃ and a relative humidity of RH75±5% for 0 days, 1, 3 and 6 months, and the accelerated stability of the valganciclovir hydrochloride oral solutions prepared in example 1 and comparative examples 1 to 4 was examined according to the guidelines of the stability test of the formulation in chinese pharmacopoeia.
Acceleration stability investigation index: valganciclovir content (%) and related substances content (%) of valganciclovir hydrochloride oral solutions at different investigation time points under the illumination condition were determined by high performance liquid chromatography.
The accelerated stability test results of valganciclovir hydrochloride oral solutions prepared in example 1 and comparative examples 1-4 at different test time points are shown in table 7:
TABLE 7 accelerated stability investigation of valganciclovir hydrochloride oral solutions prepared in example 1 and comparative examples 1-4 at 40.+ -. 2 ℃ and RH 75.+ -. 5%
From table 7, it is seen that the valganciclovir hydrochloride oral solution prepared in example 1 has excellent high temperature and high humidity acceleration stability, so that the valganciclovir hydrochloride oral solution has excellent storage and transportation stability, ensures the quality of medicine, and further effectively ensures the medication safety of the valganciclovir hydrochloride oral solution.
While the invention has been described in terms of one embodiment, it should be noted that modifications could be made without departing from the principles of the invention, which would be apparent to those skilled in the art, would also be considered to be within the scope of the invention.
Claims (5)
1. The valganciclovir hydrochloride oral solution is characterized by comprising the following components:
2. the valganciclovir hydrochloride oral solution of claim 1, wherein the valganciclovir hydrochloride oral solution consists of the following components:
3. the valganciclovir hydrochloride oral solution of claim 1, wherein the valganciclovir hydrochloride oral solution consists of the following components:
4. a process for preparing an oral solution of valganciclovir hydrochloride according to claim 1, said process comprising the steps of:
and mixing the valganciclovir hydrochloride, ethanol, glycerol, polyethylene glycol 400, sucralose, sorbitol, mannitol, lecithin, polyvinyl alcohol, tartaric acid, sodium bisulphite, sodium chloride and water to obtain the valganciclovir hydrochloride oral solution.
5. Use of valganciclovir hydrochloride oral solution according to claim 1 for the preparation of a medicament for the treatment of acquired immunodeficiency syndrome (AIDS) combined with Cytomegalovirus (CMV) retinitis.
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|---|---|---|---|---|
| CN110934823A (en) * | 2019-12-27 | 2020-03-31 | 湖北康源药业有限公司 | Valganciclovir hydrochloride oral solution and preparation method thereof |
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