CA2150462C - Syrup containing n-acetyl-cysteine - Google Patents
Syrup containing n-acetyl-cysteine Download PDFInfo
- Publication number
- CA2150462C CA2150462C CA002150462A CA2150462A CA2150462C CA 2150462 C CA2150462 C CA 2150462C CA 002150462 A CA002150462 A CA 002150462A CA 2150462 A CA2150462 A CA 2150462A CA 2150462 C CA2150462 C CA 2150462C
- Authority
- CA
- Canada
- Prior art keywords
- nac
- solution
- sodium
- syrup
- agent
- 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.)
- Expired - Lifetime
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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
- A61K9/0087—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
- A61K31/185—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/12—Mucolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Jellies, Jams, And Syrups (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
Abstract
A syrup containing N-acetyl-cysteine, stable for at least two years having pleasant taste and smell, consists of an aqueous solution of NAC, a sweetening agent and a thickening agent. The solution can also contain a flavouring agent and a preservative. The pH is between and 8.
Description
SYRUP CONTAINING N-ACETYL-CYSTEINE
The present invention relates to a composition in the form of a syrup containing N-acetyl-cysteine as active ingredient.
N-acetyl-cysteine (hereinafter briefly referred to as NAC) is a pharmacological properties, compound endowed with several useful making it a widely used drug.
In the treatment of cold diseases, NAC showed to be useful thanks to its mucolytic properties.
One of the pharmaceutical forms largely used in the therapy of cold diseases is syrup, particularly suitable also for pediatric use.
NAC is available in several pharmaceutical forms, however the high reactivity of the molecule, the relative instability and the characteristic sulphureous smell and taste make extremely troublesome the achievement of liquid forms for oral use which are time-stable and with a good palatability.
The preparation of a syrup provides, practically in ail the cases, the use of a disaccharide (sucrose) or of a simple sugar as a sweetening and thickening agent of the aqueous solution of the drug.
However, the interaction of NAC with sugars gives to the solution an unacceptable brown colouring and the titre of NAC decreases.
Thus, it is not possible to leave NAC in solution for a long time in the presence of sucrose.
Similarly, the reactions giving brown colour and causing bad smell take place also between NAC and the monosaccharides whose use is described in the French patent application No. 2631831 in the name of Calco Anstalt.
' As far,as we know, the only syrup formulation containing NAC on the market consists in a composition to be prepared at the moment of use by dissolution in water of a granulate.
After preparation, the extemporaneous syrup must be used within 3 x weeks. ' We have now surprisingly found that it is possible to prepare a time-stable NAC syrup having a pleasant taste without using sugars.
Therefore, object of the present invention is a composition in the form of a syrup containing (each 100 ml>:
- N-acetyl-cysteine 2 -4.2 g/100 mi - a sweetening agent 0.02-0.3 g/100 ml - a thickening agent selected among:
sodium carboxymethylcellulose and hydroxypropylmethylcellulose or mixtures thereof 0.1 -4 g/100 mI
and optionally:
- a flavouring agent 0.1 -0.4 g/100 mi ~5 - a preservative 0.05-0.5 g/100 ml and further - water q.s. to 10o ml pH being settled within the interval 5-8. .
The above solution results to be stable in a closed bottle under inert gas for at least 2 years under environmental conditions. When the bottle is opened, the solution shows to have a pleasant taste and to be free from bad smells; NAC maintains the initial titre and the open syrup results to be stable for at least 5 weeks.
For sweetening agent we mean a substance able to give a sweet taste to the solution but wick does not contain sugars. Specific examples of sweetening agents are saccharin, sodium saccharin and cyclamates or mixtures thereof.
The amount of sweetening agent will be the minimum amount sufficient to give a pleasant taste to the solution.
The thickening agent is selected among sodium carboxymethyicelluiose O 94/12168 ~ ~ ~ PCTIEP93/03280 methylcellulose and hydroxypropylmethyleellulose or mixtures thereof. Surprisingly, these substances showed to be compatible with NAC and to be able to give to the solution a thickness suitable for the usual palatability of a syrup.
To these three base components cNAC, sweetening agent and thickening agent) water can~be added up to the selected volume, by optionally rectifying the resultant pH so that it is maintained within the interval from 5 to 8. Preferably, pH will be from b.5 to 7.
The syrup could also, but not necessarily, contain a flavouring agent in order to improve the palatability, especially for pediatric use.
Since the syrup is generally manufactured in absence of asepsis, pharmacopoeiae require the compulsory presence of a preservative.
The preservative is further required to assure the microbioiogicai quality during the time of use by the patient.
In this case, preservatives selected among sodium benzoate, methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate and mixtures thereof will be preferably used.
With the double function of preservative and of metal cheiating agent also sodium EDTA could be used in addition to or in partial substitution of the above preservatives.
The preparation of the syrup according to the present invention is carried out under inert gas by simple dissolution of the substances in the predetermined amount of water.
The resultant solution is shared into multidose bottles or in single-dose containers.
The packaging of multi-dose bottles could provide the contemporaneous supplying of a graduated measure for the correct dosage of the single doses for grown-up people (for example 10 ml> or for children (for example 5 ml).
In order to better illustrate the present invention the following examples are now given.
Example 1 f liters of a syrup containing teach 100 ml>:
NAC 2.1 g Saccharin 0.04 g Sodium carboxymethylcellulose 0.2 g 10 Sodium benzoate 0.15 g Sodium edetate 0.1 g Raspberry flavour 0.25 g Water q.s. to 100 ml were prepared by simple dissolution of the substancespurified in and de-aerated water under nitrogen atmosphere.
The pH of the resultant solution was rectified to the correct vdiue 6.5 by addition of sodium hydroxide.
The solution was shared at the rate of 150 ml/bottle.
The bottles were stored for 2 years at room temperature.
After this period, the titre of NAC resulted to than 95i be higher of the initial one.
Such a titre resulted to be higher than 90r, of one also the initial after 5 weeks from the opening of the bottle.
The syrup, also after 2 years of storage, showed pleasant to have a taste and smell and a good general palatability.
Example 2 10 1 of a syrup having the following composition mi>:
(each 100 NAC 2.1 g Sodium saccharin 0.04 g Hydroxypropylmethylcellulose 0.2 g O 94/12168 , ~ PCT/EP93/03280 Methyl 4-hydroxybenzoate 0.1 g Sodium edetate 0.1 g Apricot flavour 0.1 g Water q.s. to 100 ml were prepared by dispersion of hydroxypropylmethylceilulose in a part of boiling water which was cooled to room temperature. After hydration of hydroxypropylmethylcellulose, it was poured into a solution obtained by dissolving all the remaining substances in purified and de-aerated water, under nitrogen atmosphere.
The pH of the solution was rectified to pH b,5 with sodium hydroxide.
The solution was shared into single-dose sachets of 10 mi each containing about 200 mg of NAC.
~5 Example 3 10 1 of a syrup having the following composition (each 100 mi>:
NAC 2.1 g Sodium saccharin 0.04 g Hydroxypropylmethylcellulose 0.2 g Sodium edetate o.1 g Apricot flavour 0.1 g Water q.s. to 100 ml were prepared by dispersion of hydroxypropylmethylcellulose in a part of boiling water which was cooled to room temperature. After hydration of hydroxypropylmethylcellulose, it was poured into a solution obtained by dissolving all the remaining substances in ' purified and de-aerated water, under nitrogen atmosphere.
The pH of the solution was rectified to pH b.5 with sodium hydroxide.
The solution was shared into single-dose glass vials of 10 mi with rubber stopper each containing about 200 mg of NAC.
Example 4 By working as described in Example 1, 10 1 of syrup having the following composition (each 100 ml> were prepared: , 4.2 g NAC
Sodium saccharin 0~08 g Sodium carboxymethylcelluiose 0.20 g Sodium benzoate 0.15 g Sodium edetate 0.10 g Raspberry flavour 0.4 g Water q.s. to 100 ml The pH of the solution was rectified to pH 6.5 with sodium hydroxide.
The solution was shared into bottles at the rate of 150 ml each bottle.
Example 5 By working as described in Example 2, 10 1 of syrup having the following composition (each 100 ml) were prepared:
20 NAC 2.1o g Saccharin 0.04 g Hydroxypropylmethylcellulose 0.40 g Methyl 4-hydroxybenzoate 0.10 g Banana flavour 0.4 g 25 Water q.s. to 100 ml G
The pH of the solution was rectified to pH 7 with sodium hydroxide.
The solution was shared into bottles at the rate of 450 mI each ' bottle.
The present invention relates to a composition in the form of a syrup containing N-acetyl-cysteine as active ingredient.
N-acetyl-cysteine (hereinafter briefly referred to as NAC) is a pharmacological properties, compound endowed with several useful making it a widely used drug.
In the treatment of cold diseases, NAC showed to be useful thanks to its mucolytic properties.
One of the pharmaceutical forms largely used in the therapy of cold diseases is syrup, particularly suitable also for pediatric use.
NAC is available in several pharmaceutical forms, however the high reactivity of the molecule, the relative instability and the characteristic sulphureous smell and taste make extremely troublesome the achievement of liquid forms for oral use which are time-stable and with a good palatability.
The preparation of a syrup provides, practically in ail the cases, the use of a disaccharide (sucrose) or of a simple sugar as a sweetening and thickening agent of the aqueous solution of the drug.
However, the interaction of NAC with sugars gives to the solution an unacceptable brown colouring and the titre of NAC decreases.
Thus, it is not possible to leave NAC in solution for a long time in the presence of sucrose.
Similarly, the reactions giving brown colour and causing bad smell take place also between NAC and the monosaccharides whose use is described in the French patent application No. 2631831 in the name of Calco Anstalt.
' As far,as we know, the only syrup formulation containing NAC on the market consists in a composition to be prepared at the moment of use by dissolution in water of a granulate.
After preparation, the extemporaneous syrup must be used within 3 x weeks. ' We have now surprisingly found that it is possible to prepare a time-stable NAC syrup having a pleasant taste without using sugars.
Therefore, object of the present invention is a composition in the form of a syrup containing (each 100 ml>:
- N-acetyl-cysteine 2 -4.2 g/100 mi - a sweetening agent 0.02-0.3 g/100 ml - a thickening agent selected among:
sodium carboxymethylcellulose and hydroxypropylmethylcellulose or mixtures thereof 0.1 -4 g/100 mI
and optionally:
- a flavouring agent 0.1 -0.4 g/100 mi ~5 - a preservative 0.05-0.5 g/100 ml and further - water q.s. to 10o ml pH being settled within the interval 5-8. .
The above solution results to be stable in a closed bottle under inert gas for at least 2 years under environmental conditions. When the bottle is opened, the solution shows to have a pleasant taste and to be free from bad smells; NAC maintains the initial titre and the open syrup results to be stable for at least 5 weeks.
For sweetening agent we mean a substance able to give a sweet taste to the solution but wick does not contain sugars. Specific examples of sweetening agents are saccharin, sodium saccharin and cyclamates or mixtures thereof.
The amount of sweetening agent will be the minimum amount sufficient to give a pleasant taste to the solution.
The thickening agent is selected among sodium carboxymethyicelluiose O 94/12168 ~ ~ ~ PCTIEP93/03280 methylcellulose and hydroxypropylmethyleellulose or mixtures thereof. Surprisingly, these substances showed to be compatible with NAC and to be able to give to the solution a thickness suitable for the usual palatability of a syrup.
To these three base components cNAC, sweetening agent and thickening agent) water can~be added up to the selected volume, by optionally rectifying the resultant pH so that it is maintained within the interval from 5 to 8. Preferably, pH will be from b.5 to 7.
The syrup could also, but not necessarily, contain a flavouring agent in order to improve the palatability, especially for pediatric use.
Since the syrup is generally manufactured in absence of asepsis, pharmacopoeiae require the compulsory presence of a preservative.
The preservative is further required to assure the microbioiogicai quality during the time of use by the patient.
In this case, preservatives selected among sodium benzoate, methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate and mixtures thereof will be preferably used.
With the double function of preservative and of metal cheiating agent also sodium EDTA could be used in addition to or in partial substitution of the above preservatives.
The preparation of the syrup according to the present invention is carried out under inert gas by simple dissolution of the substances in the predetermined amount of water.
The resultant solution is shared into multidose bottles or in single-dose containers.
The packaging of multi-dose bottles could provide the contemporaneous supplying of a graduated measure for the correct dosage of the single doses for grown-up people (for example 10 ml> or for children (for example 5 ml).
In order to better illustrate the present invention the following examples are now given.
Example 1 f liters of a syrup containing teach 100 ml>:
NAC 2.1 g Saccharin 0.04 g Sodium carboxymethylcellulose 0.2 g 10 Sodium benzoate 0.15 g Sodium edetate 0.1 g Raspberry flavour 0.25 g Water q.s. to 100 ml were prepared by simple dissolution of the substancespurified in and de-aerated water under nitrogen atmosphere.
The pH of the resultant solution was rectified to the correct vdiue 6.5 by addition of sodium hydroxide.
The solution was shared at the rate of 150 ml/bottle.
The bottles were stored for 2 years at room temperature.
After this period, the titre of NAC resulted to than 95i be higher of the initial one.
Such a titre resulted to be higher than 90r, of one also the initial after 5 weeks from the opening of the bottle.
The syrup, also after 2 years of storage, showed pleasant to have a taste and smell and a good general palatability.
Example 2 10 1 of a syrup having the following composition mi>:
(each 100 NAC 2.1 g Sodium saccharin 0.04 g Hydroxypropylmethylcellulose 0.2 g O 94/12168 , ~ PCT/EP93/03280 Methyl 4-hydroxybenzoate 0.1 g Sodium edetate 0.1 g Apricot flavour 0.1 g Water q.s. to 100 ml were prepared by dispersion of hydroxypropylmethylceilulose in a part of boiling water which was cooled to room temperature. After hydration of hydroxypropylmethylcellulose, it was poured into a solution obtained by dissolving all the remaining substances in purified and de-aerated water, under nitrogen atmosphere.
The pH of the solution was rectified to pH b,5 with sodium hydroxide.
The solution was shared into single-dose sachets of 10 mi each containing about 200 mg of NAC.
~5 Example 3 10 1 of a syrup having the following composition (each 100 mi>:
NAC 2.1 g Sodium saccharin 0.04 g Hydroxypropylmethylcellulose 0.2 g Sodium edetate o.1 g Apricot flavour 0.1 g Water q.s. to 100 ml were prepared by dispersion of hydroxypropylmethylcellulose in a part of boiling water which was cooled to room temperature. After hydration of hydroxypropylmethylcellulose, it was poured into a solution obtained by dissolving all the remaining substances in ' purified and de-aerated water, under nitrogen atmosphere.
The pH of the solution was rectified to pH b.5 with sodium hydroxide.
The solution was shared into single-dose glass vials of 10 mi with rubber stopper each containing about 200 mg of NAC.
Example 4 By working as described in Example 1, 10 1 of syrup having the following composition (each 100 ml> were prepared: , 4.2 g NAC
Sodium saccharin 0~08 g Sodium carboxymethylcelluiose 0.20 g Sodium benzoate 0.15 g Sodium edetate 0.10 g Raspberry flavour 0.4 g Water q.s. to 100 ml The pH of the solution was rectified to pH 6.5 with sodium hydroxide.
The solution was shared into bottles at the rate of 150 ml each bottle.
Example 5 By working as described in Example 2, 10 1 of syrup having the following composition (each 100 ml) were prepared:
20 NAC 2.1o g Saccharin 0.04 g Hydroxypropylmethylcellulose 0.40 g Methyl 4-hydroxybenzoate 0.10 g Banana flavour 0.4 g 25 Water q.s. to 100 ml G
The pH of the solution was rectified to pH 7 with sodium hydroxide.
The solution was shared into bottles at the rate of 450 mI each ' bottle.
Claims (7)
1. A composition in the form of a syrup containing (each 100 ml):
- N-acetyl-cysteine ~~~~2 - 4.2 g/100ml - a sweetening agent ~~~0.02 - 0.3 g/100ml - a thickening agent selected among:
sodium carboxymethylcellulose and hydroxypropylmethylcellulose or mixtures thereof ~~~~0.1 - 4 g/100ml and further - water q.s. to 100 ml pH being settled within the interval 5-8.
- N-acetyl-cysteine ~~~~2 - 4.2 g/100ml - a sweetening agent ~~~0.02 - 0.3 g/100ml - a thickening agent selected among:
sodium carboxymethylcellulose and hydroxypropylmethylcellulose or mixtures thereof ~~~~0.1 - 4 g/100ml and further - water q.s. to 100 ml pH being settled within the interval 5-8.
2. A composition according to claim 1, wherein said composition further contains a flavouring agent in an amount of (0.1 - 0.4 g/100ml).
3. A composition according to claim 1, wherein said composition further contains a preservative in an amount of (0.05 - 0.5 g/100ml).
4. A composition according to claim 1, wherein said composition further contains a flavouring agent in the amount of (0.1 - 0.4 g/100ml) and a preservative in the amount of (0.05 - 0.5 g/100ml).
5. A composition according to claim 3 or claim 4, wherein said preservative is selected from the group consisting of sodium edetate, sodium benzoate, methyl hydroxybenzoate, propyl 4-hydroxybenzoate and mixtures thereof.
6. A composition according to any one of claims 1 to 5, wherein said sweetening agent is selected from the group consisting of saccharin, sodium saccharin, and cyclamates or mixtures thereof.
7. A composition according to any one of claims 1 to 6, wherein the pH is between 6.5 and 7.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI92A002758 | 1992-12-02 | ||
| ITMI922758A IT1256616B (en) | 1992-12-02 | 1992-12-02 | SYRUP CONTAINING N-ACETYL-CISTEIN |
| PCT/EP1993/003280 WO1994012168A1 (en) | 1992-12-02 | 1993-11-23 | Syrup containing n-acetyl-cysteine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2150462A1 CA2150462A1 (en) | 1994-06-09 |
| CA2150462C true CA2150462C (en) | 2005-04-19 |
Family
ID=11364395
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002150462A Expired - Lifetime CA2150462C (en) | 1992-12-02 | 1993-11-23 | Syrup containing n-acetyl-cysteine |
Country Status (23)
| Country | Link |
|---|---|
| JP (1) | JPH08503703A (en) |
| AT (1) | AT407113B (en) |
| AU (1) | AU667611B2 (en) |
| BE (1) | BE1006799A3 (en) |
| CA (1) | CA2150462C (en) |
| CH (1) | CH685371A5 (en) |
| CZ (1) | CZ282550B6 (en) |
| DE (2) | DE4396086B3 (en) |
| DK (1) | DK176247B1 (en) |
| ES (1) | ES2070806B1 (en) |
| FR (1) | FR2698545B1 (en) |
| GB (1) | GB2288977B (en) |
| HU (2) | HU221484B (en) |
| IT (1) | IT1256616B (en) |
| LU (1) | LU88618A1 (en) |
| MD (1) | MD1714G2 (en) |
| NL (1) | NL194957C (en) |
| NO (1) | NO314018B1 (en) |
| NZ (1) | NZ258544A (en) |
| RU (1) | RU2108777C1 (en) |
| SE (1) | SE520834C2 (en) |
| UA (1) | UA27142C2 (en) |
| WO (1) | WO1994012168A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10502355A (en) * | 1994-06-23 | 1998-03-03 | ザ、プロクター、エンド、ギャンブル、カンパニー | Topical composition containing N-acetyl-L-cysteine |
| JP4501023B2 (en) * | 2002-11-14 | 2010-07-14 | 小林製薬株式会社 | Composition with reduced bitterness and odor of cysteines |
| JP4501024B2 (en) * | 2002-11-14 | 2010-07-14 | 小林製薬株式会社 | Composition with reduced bitterness and odor of cysteines |
| US8148356B2 (en) * | 2005-08-24 | 2012-04-03 | Cumberland Pharmaceuticals, Inc. | Acetylcysteine composition and uses therefor |
| CN102233139B (en) * | 2010-04-21 | 2012-09-05 | 重庆健能医药开发有限公司 | Acetylcysteine effervescent tablet and preparation method and application thereof |
| RU2611411C1 (en) * | 2016-01-11 | 2017-02-21 | Общество с ограниченной ответственностью "Трейдсервис" | Dispersible in water acetylcysteine tablet and method of manufacturing thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB905197A (en) * | 1960-01-01 | 1962-09-05 | Lab Francais Chimiotherapie | Anti-viral compositions comprising 1-phenyl-2-amino-propane-1,3-diol derivatives |
| CA1239349A (en) * | 1983-10-10 | 1988-07-19 | Eberhard F. Gottwald | Pharmaceutical composition containing cimetidine |
| BE901885A (en) * | 1985-03-06 | 1985-07-01 | Bruschettini Srl | Stable ophthalmic soln. contg. N-acetyl-cysteine - prepd. in nitrogen satd. aq. buffer free of metal ions |
| CH667590A5 (en) * | 1986-07-24 | 1988-10-31 | Inpharzam Int Sa | WATER-SOLUBLE EFFERVESCENT PHARMACEUTICAL COMPOSITION CONTAINING N-ACETYL-CISTEIN. . |
| CH666814A5 (en) * | 1986-07-24 | 1988-08-31 | Inpharzam Int Sa | WATER-SOLUBLE PHARMACEUTICAL COMPOSITION CONTAINING N-ACETYL-CISTEIN. |
| US4861797A (en) * | 1987-10-15 | 1989-08-29 | Oratech Pharmaceutical Development Corporation | Liquid ibuprofen compositions and methods of making them |
| CH674940A5 (en) * | 1988-05-05 | 1990-08-15 | Ibsa Inst Biochimique Sa | |
| IT1234194B (en) * | 1988-05-31 | 1992-05-06 | Magis Farmaceutici | SYRUP PHARMACEUTICAL COMPOSITIONS CONTAINING PENTITLES AS VEHICULATING AGENTS |
| ATE87476T1 (en) * | 1988-11-10 | 1993-04-15 | Ciba Geigy Ag | LIQUID ORAL FORMULATION. |
| IT1231012B (en) * | 1989-07-27 | 1991-11-08 | Zambon Spa | PHARMACEUTICAL COMPOSITION FOR ORAL USE CONTAINING NAC. |
| IT1248998B (en) * | 1990-06-26 | 1995-02-11 | Iscofar Sas | COMPOSITION OF RUBBER TO BE CHEWED FOR THE PREVENTION AND TREATMENT OF DENTAL PLATE |
| DK0481294T4 (en) * | 1990-10-19 | 2001-06-18 | Spirig Ag | Solid, fast-soluble drug preparation containing N-acetylcysteine |
-
1992
- 1992-12-02 IT ITMI922758A patent/IT1256616B/en active IP Right Grant
-
1993
- 1993-11-23 JP JP6512747A patent/JPH08503703A/en active Pending
- 1993-11-23 CH CH2423/94A patent/CH685371A5/en not_active IP Right Cessation
- 1993-11-23 RU RU95114406A patent/RU2108777C1/en active
- 1993-11-23 CZ CZ951367A patent/CZ282550B6/en not_active IP Right Cessation
- 1993-11-23 AT AT0906093A patent/AT407113B/en not_active IP Right Cessation
- 1993-11-23 DE DE4396086A patent/DE4396086B3/en not_active Expired - Lifetime
- 1993-11-23 AU AU56266/94A patent/AU667611B2/en not_active Expired
- 1993-11-23 GB GB9509822A patent/GB2288977B/en not_active Expired - Lifetime
- 1993-11-23 WO PCT/EP1993/003280 patent/WO1994012168A1/en active IP Right Grant
- 1993-11-23 ES ES09450021A patent/ES2070806B1/en not_active Expired - Fee Related
- 1993-11-23 MD MD96-0265A patent/MD1714G2/en unknown
- 1993-11-23 NZ NZ258544A patent/NZ258544A/en not_active IP Right Cessation
- 1993-11-23 NL NL9320052A patent/NL194957C/en not_active IP Right Cessation
- 1993-11-23 CA CA002150462A patent/CA2150462C/en not_active Expired - Lifetime
- 1993-11-23 UA UA95062994A patent/UA27142C2/en unknown
- 1993-11-23 HU HU9501586A patent/HU221484B/en unknown
- 1993-11-23 DE DE4396086T patent/DE4396086T1/en active Pending
- 1993-12-01 BE BE9301326A patent/BE1006799A3/en not_active IP Right Cessation
- 1993-12-02 FR FR9314443A patent/FR2698545B1/en not_active Expired - Lifetime
-
1994
- 1994-05-24 LU LU88618A patent/LU88618A1/en unknown
-
1995
- 1995-05-31 DK DK199500614A patent/DK176247B1/en not_active IP Right Cessation
- 1995-06-01 NO NO19952183A patent/NO314018B1/en not_active IP Right Cessation
- 1995-06-01 SE SE9502001A patent/SE520834C2/en not_active IP Right Cessation
- 1995-06-29 HU HU95P/P00579P patent/HU211912A9/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20131125 |