CN106389313A - Baclofen oral liquid composition - Google Patents
Baclofen oral liquid composition Download PDFInfo
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- CN106389313A CN106389313A CN201610876029.5A CN201610876029A CN106389313A CN 106389313 A CN106389313 A CN 106389313A CN 201610876029 A CN201610876029 A CN 201610876029A CN 106389313 A CN106389313 A CN 106389313A
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- Prior art keywords
- baclofen
- oral liquid
- solution
- essence
- purified water
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- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 229960000794 baclofen Drugs 0.000 title claims abstract description 49
- 239000007788 liquid Substances 0.000 title claims abstract description 39
- 239000000203 mixture Substances 0.000 title claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000008213 purified water Substances 0.000 claims abstract description 15
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims abstract description 9
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims abstract description 9
- 229960002216 methylparaben Drugs 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 239000004376 Sucralose Substances 0.000 claims abstract description 8
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims abstract description 8
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims abstract description 8
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims abstract description 8
- 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 8
- 235000019408 sucralose Nutrition 0.000 claims abstract description 8
- 239000000243 solution Substances 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 9
- 239000007853 buffer solution Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 239000012467 final product Substances 0.000 claims description 4
- 239000003002 pH adjusting agent Substances 0.000 claims description 4
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 claims description 4
- HFEWAGKDZLEFCT-UHFFFAOYSA-L C(C)C(COP(=O)(OCC(CCCC)CC)[O-])CCCC.P(=O)(O)([O-])O.[Na+].[Na+] Chemical compound C(C)C(COP(=O)(OCC(CCCC)CC)[O-])CCCC.P(=O)(O)([O-])O.[Na+].[Na+] HFEWAGKDZLEFCT-UHFFFAOYSA-L 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 2
- 240000009088 Fragaria x ananassa Species 0.000 claims description 2
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 claims description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 claims description 2
- 240000006365 Vitis vinifera Species 0.000 claims description 2
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 2
- -1 disodium hydrogen Chemical class 0.000 claims description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- GHEZNRQAMLNCNT-UHFFFAOYSA-N C(=O)OCCC.OC1=CC=CC=C1 Chemical compound C(=O)OCCC.OC1=CC=CC=C1 GHEZNRQAMLNCNT-UHFFFAOYSA-N 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 claims 1
- 239000002304 perfume Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 238000011282 treatment Methods 0.000 description 5
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 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 description 1
- 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 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010019468 Hemiplegia Diseases 0.000 description 1
- 208000031361 Hiccup Diseases 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010041415 Spastic paralysis Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- JKCNXKXYMRTCQZ-UHFFFAOYSA-N pentane-1-sulfonic acid;sodium Chemical compound [Na].CCCCCS(O)(=O)=O JKCNXKXYMRTCQZ-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000012201 sexual and gender identity disease Diseases 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
Classifications
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- 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
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- 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
- A61K47/26—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
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a baclofen oral liquid composition and a preparation method thereof. Baclofen oral liquid contains baclofen, methylparaben, propyl p-hydroxybenzoate, sucralose, a pH regulator, aromatics and purified water. The baclofen oral liquid has the advantages of simple process, good taste and good stability.
Description
Technical field
The present invention relates to a kind of baclofen oral liquid compositionss and preparation method thereof, belong to technical field of medicine.
Background technology
Baclofen is researched and developed by Medtronic company of the U.S., lists in the U.S. first within 1992, is first and is applied to face
The selectivity GABA beta receptor agonist of bed.Hemiplegia that baclofen causes after cerebrovascular disease and apoplexy, spinal cord injury convulsion
Good therapeutic effect is obtained in the clinical treatments such as the central spastic paralysiss that the disease such as contraction and multiple sclerosiss causes.Also
Have many other applications, such as treatment central intractable singultuss and neuropathic pain, treatment dysfunctional urinate and spinal cord injury after
Urinary function sexual disorders, treatment reduces to the dependency of the addicted substances such as tobacco and wine and morphine, treatment non-acid gastroesophageal reflux
Property cough etc..
The dosage form of baclofen selection of clinical has tablet, injection and oral liquid.Its oral liquid lists in multiple country of European Union,
Safely and effectively.Due to baclofen poorly water-soluble, tablet is difficult to dissolution, so that medicine does not reach due therapeutical effect.And mouth
Then bioavailability is high to take solution, and is particularly suitable for child and dysphagia patien's use.But baclofen is in liquid preparation
Stability poor, research worker was attempted adding some stabilizers strengthening the stability of baclofen, but effect is undesirable, or
There is degradation impurity.
Oral liquid is to be suitable for child and dysphagia patients（As old man）The dosage form using, but find no in prior art
The development report of baclofen oral liquid.In addition, there is prescription complexity in the baclofen oral liquid of European Union's listing（As containing substantial amounts of mountain
Pears alcohol, propylene glycol, hydroxyethyl cellulose or sodium carboxymethyl cellulose etc.）, poor taste, stability difference the shortcomings of.Therefore, select
Appropriate adjuvant, overcomes the deficiencies in the prior art, prepares a kind of in good taste, baclofen of Functionality, quality and appealing design, good stability, process is simple
Oral liquid is to need those skilled in the art to put forth effort the technical problem solving.
Content of the invention
Through numerous studies, it has been surprisingly found that baclofen and sucralose, suitable preservative and edible essence phosphorus
Sour disodium hydrogen-phosphate sodium dihydrogen buffer solution adjusts pH value, and to be that the baclofen oral liquid made after 5.8～6.3 has good steady
Qualitative and mouthfeel.Particularly, the baclofen oral liquid of the present invention in the range of certain content for each component has close to beverage
Mouthfeel and high quality and stability.
Based on this, we are prepared in good taste, Functionality, quality and appealing design, good stability baclofen oral liquid, achieve unexpected
Effect, and then complete the present invention.
The first object of the present invention is to provide a kind of baclofen oral liquid compositionss, and specific technical scheme is as follows：
A kind of baclofen oral liquid compositionss, including baclofen, methyl parahydroxybenzoate, propyl p-hydroxybenzoate, trichlorine
Sucrose, pH adjusting agent, aromatic and purified water composition；Wherein pH adjusting agent is disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution,
And pH value is 5.8～6.3；In addition, aromatic is edible essence, selected from strawberry essence, Fructus Citri tangerinae essence, grape essence, NINGMENGXIANG
One of essence, essence for organi juice or its mixture；More specifically, this baclofen oral liquid compositions, every 100ml by baclofen 100mg,
Methyl parahydroxybenzoate 20～30mg, propyl p-hydroxybenzoate 20～30mg, sucralose 40～60mg, edible essence 10
～20mg, disodium hydrogen phosphate-appropriate phosphate sodium dihydrogen buffer solution and suitable quantity of water composition.
The second object of the present invention is the preparation method providing above-mentioned baclofen oral liquid, and specific technical scheme is as follows：
1）Appropriate purified water is heated to 70 ± 5 DEG C, adds methyl parahydroxybenzoate, propyl p-hydroxybenzoate stirring molten
Solution；
2）Baclofen is added in appropriate 70 ± 5 DEG C of purified water, stirs into suspension solution；
3）Under agitation, by step 1）Solution be slowly added to step 2）Solution in, with appropriate disodium hydrogen phosphate-di(2-ethylhexyl)phosphate
Hydrogen sodium buffer adjusts pH value to being completely dissolved；
4）To step 3）Solution in add sucralose and edible essence, be cooled to room temperature, plus purified water, to full dose, use phosphoric acid
Disodium hydrogen-phosphate sodium dihydrogen buffer solution regulation pH value to 5.8～6.3；
5）By step 4）Solution, filtered with 0.45 μm of plate filter, fill, sterilizing, obtain final product baclofen oral liquid.
The baclofen oral liquid scientific formula of the present invention, rationally, drastically increases the stability of baclofen oral liquid, produces
Give birth to unforeseeable technique effect.Additionally, the present invention does not contain the thickening agent such as hydroxyethyl cellulose, sodium carboxymethyl cellulose and third
The cosolvents such as glycol, preparation process is simple, cost is relatively low.
Specific embodiment
Specific embodiment only further explains and describes the present invention, is not necessarily to be construed as any limit to the present invention
System.If no special instructions, in following examples, method therefor is conventional method.
The preparation of embodiment 1～8 baclofen oral liquid
Prescription：
Specification 100ml/ bottle, makes 1000 bottles
Embodiment preparation technology：
1）Appropriate purified water is heated to 70 ± 5 DEG C, adds methyl parahydroxybenzoate, propyl p-hydroxybenzoate stirring molten
Solution；
2）Baclofen is added in appropriate 70 ± 5 DEG C of purified water, stirs into suspension solution；
3）Under agitation, by step 1）Solution be slowly added to step 2）Solution in, with appropriate disodium hydrogen phosphate-di(2-ethylhexyl)phosphate
Hydrogen sodium buffer adjusts pH value to being completely dissolved；
4）To step 3）Solution in add sucralose and edible essence, be cooled to room temperature, plus purified water, to full dose, use phosphoric acid
Disodium hydrogen-phosphate sodium dihydrogen buffer solution regulation pH value to 5.8～6.3；
5）By step 4）Solution, filtered with 0.45 μm of plate filter, fill, sterilizing, obtain final product.
Comparative examples preparation technology：
1）Appropriate purified water is heated to 70 ± 5 DEG C, adds methyl parahydroxybenzoate, propyl p-hydroxybenzoate stirring molten
Solution；
2）Baclofen is added in appropriate 70 ± 5 DEG C of purified water, stirs into suspension solution；
3）Under agitation, by step 1）Solution be slowly added to step 2）Solution in, add recipe quantity hydroxyethyl cellulose,
Sodium carboxymethyl cellulose, Sorbitol, propylene glycol stir to being completely dissolved；
4）To step 3）Solution in add edible essence, be cooled to room temperature, plus purified water be to full dose,
5）By step 4）Solution, filtered with 0.45 μm of plate filter, fill, sterilizing, obtain final product.
The stability study of embodiment 9 baclofen oral liquid
Required according to 2015 editions two annex XIX C stability test guidelines of Chinese Pharmacopoeia, investigate embodiment 1～8 and be obtained
Baclofen oral liquid stability, adopt high performance liquid chromatography about material and content【Method：Use octadecylsilane key
Conjunction silica gel is filler（4.6mm × 250mm, 5 μm or the suitable chromatographic column of efficiency）, with 0.3mo1/L glacial acetic acid solution one methanol
One 0.36mo1/L pentanesulfonic acid sodium solution (550：440：20) it is mobile phase, Detection wavelength is 265nm, column temperature is 30 DEG C, impurity
A and third peak of 4-HBA fly separating degree and are not less than 5.0】, the results are shown in Table 1～3：
Table 0 day testing result of 1 baclofen oral liquid：
Table 2 baclofen oral liquid accelerated test result（Simulation commercially available back, 2 DEG C of 40 DEG C of scholars of temperature, relative humidity 75% scholar
5%, place 6 months）
Table 3 baclofen oral liquid long-term stable experiment result（Simulation commercially available back, 2 DEG C of 25 DEG C of scholars of temperature, relatively wet
Spend 60% scholar 10%, place 12 months）
In summary, in acceleration and in terms of long-time stability, the baclofen oral liquid of the present invention（Embodiment 1～6 is substantially excellent
In reference examples 7～8）.
Claims (6)
1. a kind of baclofen oral liquid compositionss are it is characterised in that include baclofen, methyl parahydroxybenzoate, para hydroxybenzene
Propyl formate, sucralose, pH adjusting agent, aromatic and purified water composition.
2. baclofen oral liquid compositionss according to claim 1 are it is characterised in that described pH adjusting agent is phosphoric acid hydrogen
Disodium-phosphate sodium dihydrogen buffer solution.
3. baclofen oral liquid compositionss according to claim 1 are it is characterised in that the pH of described oral liquid compositionss
It is worth for 5.8～6.3.
4. baclofen oral liquid compositionss according to claim 1 are it is characterised in that described aromatic is edible perfume
Essence, selected from one of strawberry essence, Fructus Citri tangerinae essence, grape essence, Fructus Citri Limoniae essence, essence for organi juice or its mixture.
5. a kind of baclofen oral liquid compositionss described in claim 1 are it is characterised in that every oral liquid group described in 100ml
Compound is by baclofen 100mg, methyl parahydroxybenzoate 20～30mg, propyl p-hydroxybenzoate 20～30mg, sucralose
40～60mg, edible essence 10～20mg, disodium hydrogen phosphate-appropriate phosphate sodium dihydrogen buffer solution and suitable quantity of water composition.
6. the preparation method of the baclofen oral liquid described in any one of Claims 1 to 5 is it is characterised in that comprise the steps：
1）Appropriate purified water is heated to 70 ± 5 DEG C, adds methyl parahydroxybenzoate, propyl p-hydroxybenzoate stirring molten
Solution；
2）Baclofen is added in appropriate 70 ± 5 DEG C of purified water, stirs into suspension solution；
3）Under agitation, by step 1）Solution be slowly added to step 2）Solution in, with appropriate disodium hydrogen phosphate-di(2-ethylhexyl)phosphate
Hydrogen sodium buffer adjusts pH value to being completely dissolved；
4）To step 3）Solution in add sucralose and edible essence, be cooled to room temperature, plus purified water, to full dose, use phosphoric acid
Disodium hydrogen-phosphate sodium dihydrogen buffer solution regulation pH value to 5.8～6.3；
5）By step 4）Solution, filtered with 0.45 μm of plate filter, fill, sterilizing, obtain final product baclofen oral liquid.
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| CN201610876029.5A CN106389313A (en) | 2016-10-08 | 2016-10-08 | Baclofen oral liquid composition |
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| CN201610876029.5A CN106389313A (en) | 2016-10-08 | 2016-10-08 | Baclofen oral liquid composition |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107034174A (en) * | 2017-06-15 | 2017-08-11 | 重庆市畜牧科学院 | A kind of novel mouse zona pellucida removes reagent and its preparation method and application |
| WO2020242543A1 (en) * | 2019-05-27 | 2020-12-03 | Slayback Pharma Llc | Liquid pharmaceutical compositions of baclofen for oral administration |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105473131A (en) * | 2013-06-05 | 2016-04-06 | 法奈克斯公司 | Stable oral solutions for combined API |
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2016
- 2016-10-08 CN CN201610876029.5A patent/CN106389313A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105473131A (en) * | 2013-06-05 | 2016-04-06 | 法奈克斯公司 | Stable oral solutions for combined API |
Non-Patent Citations (1)
| Title |
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| ALLEN,LOYD V.JR ET AL.: ""Stability of baclofen, captopril, diltiazem hydrochloride, dipyridamole, and flecainide acetate in extemporaneously compounded oral liquids"", 《AM J HEALTH-SYST PHARM》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107034174A (en) * | 2017-06-15 | 2017-08-11 | 重庆市畜牧科学院 | A kind of novel mouse zona pellucida removes reagent and its preparation method and application |
| CN107034174B (en) * | 2017-06-15 | 2020-07-28 | 重庆市畜牧科学院 | A novel mouse embryo zona removal reagent and preparation method and application thereof |
| WO2020242543A1 (en) * | 2019-05-27 | 2020-12-03 | Slayback Pharma Llc | Liquid pharmaceutical compositions of baclofen for oral administration |
| US10952981B2 (en) | 2019-05-27 | 2021-03-23 | Slayback Pharma Llc | Liquid pharmaceutical compositions of baclofen for oral administration |
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