CN106389313A - Baclofen oral liquid composition - Google Patents
Baclofen oral liquid composition Download PDFInfo
- Publication number
- 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
- Authority
- CN
- China
- Prior art keywords
- baclofen
- oral liquid
- solution
- essence
- purified water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610876029.5A CN106389313A (en) | 2016-10-08 | 2016-10-08 | Baclofen oral liquid composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610876029.5A CN106389313A (en) | 2016-10-08 | 2016-10-08 | Baclofen oral liquid composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106389313A true CN106389313A (en) | 2017-02-15 |
Family
ID=59228096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610876029.5A Pending CN106389313A (en) | 2016-10-08 | 2016-10-08 | Baclofen oral liquid composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106389313A (en) |
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 |
-
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 |
|---|
| 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 | Novel mouse embryo zona pellucida removing 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 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6952143B2 (en) | Topical formulation of JAK inhibitor | |
| ES2640572T3 (en) | Enhanced parenteral formulations of lipophilic pharmaceutical agents and methods of preparation and use thereof | |
| JP3569916B2 (en) | Pharmaceutical products for the treatment of tumors and methods for their production | |
| CN103893186B (en) | For treating cancer and Other diseases or the medical composition of illness | |
| US11116811B2 (en) | Pharmaceutical composition comprising refined indigo naturalis extracts and the use thereof | |
| BR112013004698B1 (en) | Pharmaceutical compositions comprising poh derivatives | |
| CN103702975B (en) | ENCLO metabolite and uses thereof | |
| BR112013015107B1 (en) | Pharmaceutical composition, use of an isoperyl alcohol or an isoperyl alcohol carbamate and process for producing an isoperyl alcohol carbamate | |
| US11897875B2 (en) | Deuterated Alpha5 subunit-selective negative allosteric modulators of gamma-aminobutyric acid type a receptors as fast acting treatment for depression and mood disorders | |
| CN106389313A (en) | Baclofen oral liquid composition | |
| CN105078909B (en) | Cisatracurium besilate freeze-dried composition for injection and preparation method thereof | |
| KR101189763B1 (en) | Composition comprising linalool for prevention, treatment, or improvement of central nervous system disorders | |
| CN102892289B (en) | Pharmaceutical compositions comprising monoterpenes | |
| EP2389171A2 (en) | Use of pterosin compounds for treating diabetes and obesity | |
| CN105814072B (en) | A kind of pentacyclic triterpene structure modified compound and its preparation method and application | |
| CN114555056B (en) | Small molecule PI4KIII alpha inhibitor composition, preparation method and application thereof | |
| CN110927279B (en) | Method for separating imidapril hydrochloride related substances | |
| IL276838A (en) | Oral formulation and suspension of an oncology drug | |
| CN110139641B (en) | External composition | |
| CN107049936B (en) | Amplification production method of the benzene sulphur containing preservative along atracurium injection | |
| CN106692039B (en) | Agomelatine oral liquid preparation and preparation method and application thereof | |
| EP2886125B1 (en) | Pharmaceutical composition increasing cyclic amp content and availability in vivo, and preparation method thereof | |
| BE1025934A1 (en) | PHARMACEUTICAL SUSPENSION OF METHYLPREDNISOLONE | |
| CN103896743B (en) | A kind of preparation method of 2,6 diisopropyl, 4 fluorophenol | |
| CN107753481A (en) | A kind of western smooth class pharmaceutical composition containing buffer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170215 |
|
| WD01 | Invention patent application deemed withdrawn after publication |