IE41628B1 - New erythromycin salt process for preparing it and compositions incorporating it - Google Patents
New erythromycin salt process for preparing it and compositions incorporating itInfo
- Publication number
- IE41628B1 IE41628B1 IE147275A IE147275A IE41628B1 IE 41628 B1 IE41628 B1 IE 41628B1 IE 147275 A IE147275 A IE 147275A IE 147275 A IE147275 A IE 147275A IE 41628 B1 IE41628 B1 IE 41628B1
- Authority
- IE
- Ireland
- Prior art keywords
- erythromycin
- pyroglutamate
- pharmaceutical composition
- water
- vehicle
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D207/28—2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
1485210 Compositions containing erythromycin pyroglutamate ROUSSEL-UCLAF 2 July 1975 [2 July 1974] 27809/75 Heading A5B [Also in Division C2] Pharmaceutical compositions having bacteriostatic and bactericidal activity comprise, as active ingredient, erythromycin pyroglutamate, in association with a suitable pharmaceutical vehicle and optionally other active ingredients such as erythromycin base and a colistin salt, e.g. the sulphate. They may be administered orally, perlingually, topically or transcutaneously in the form of tablets, capsules, injectable solutions or suspensions, creams or ointments.
Description
This invention relates to a new erythromycin salt, erythromycin pyroglutamate, which may be of use in human or veterinary medicine.
Thus, in one aspect this invention provides erythromycin 5 pyroglutamate.
The invention also provides a process for preparing erythromycin pyroglutamate, in which pyroglutamic acid is reacted with erythromycin base to give the desired erythromycin pyroglutamate.
Preferably this process is carried out by reacting the pyroglutamic acid with a stoichiometric quantity or an excess of erythromycin base, the pH of the reaction mixture being
7.1 or greater. The reaction is also most conveniently performed in a solvent such as distilled water, anhydrous acetone or methyl ethyl ketone saturated with water. Using these preferred conditions the partial degradation of the erythromycin into active anhydroerythromycin may be avoided.
When excess erythromycin base is used in the preparation, the unreacted erythromycin base may thereafter be removed by filtration, and a filtrate containing the desired pyroglutam ate recovered.
The erythromycin pyroglutamate may be isolated by the usual methods employed for compounds of this type, and the selection and operation of these isolation methods are believed to be within the competence of one skilled in the art. A preferred isolation technique is lyophilisation.
This invention provides, in addition, an alternative process for the preparation of erythromycin pyroglutamate, in which a soluble salt of erythromycin and a soluble salt of pyroglutamic acid are reacted to give, by double decomposition, the desired erythromycin pyroglutamate. This double decomposition is preferably carried in a medium consisting of water and an organic solvent not totally miscible with water. Examples of suitable organic solvents include lower alkyl (C^_g) acetates and chlorinated organic solvents.
This invention extends, of course, to erythromycin pyroglutamate whenever prepared by a process as described and claimed herein.
It has been found that erythromycin pyroglutamate is endowed with important bacteriostatic and bactericidal activity, lb especially against Gram (+) germs, an activity which may make it useful in human and veterinary medicine as a medicament.
The compound of the invention may be of particular use in the control of diseases caused by germs sensitive to erythromycin, such as gastroenteritis, infectious enteritis, intestinal diseases, septicemia, infections of the respiratory tract (for example, pneumonia), infections of the ear, nose and throat (for example, sinusitis), and streptococcal or staphylococcal skin infections (for example, boils).
While the dosages of erythromycin pyroglutamate in human therapy will, to a certain degree, depend upon the route of administration, the subject being treated and the complaint concerned, by way of illustration it may be said that in human therapy the useful dosage ranges from 100 mg to 2 g per day by oral route for an adult. In veterinary therapy, the useful dosage again, of course, varies according to the route of administration, the animal being treated and the complaint concerned, but may be, for example, from 50 mg to 1 g per day for a calf when administered by injection.
However, before any of the compounds of this invention are used in medicine, they are preferably formed into pharmac10 eutical compositions by association with suitable pharmaceutical vehicles.
The term pharmaceutical is used herein to exclude any possibility that the nature of the vehicle, considered of course, in relation to the route by which the composition is intended to be administered, could be harmful rather than beneficial. The choice of a suitable mode of presentation, together with an appropriate vehicle, is believed to be within the competence of those accustomed to the preparation of pharmaceutical formulations.
Accordingly, in another aspect, this invention provides pharmaceutical compositions containing, as active principle, erythromycin pyroglutamate, either alone or in combination with other active ingredients, in association with a suitable pharmaceutical vehicle.
The compositions of this invention may be administered orally, perlingually, topically or transcutaneously, and in respect of these modes, the pharmaceutical vehicle is preferably:4
a) the ingestible excipient of a tablet, coated tablet, sublingual table or pill; the ingestible container of a capsule or cachet; the ingestible pulverulent carrier of a powder; or the ingestible liquid medium of a syrup, solution, suspension or elixir;
b) the solid or liquid medium of a paste, lotion, salve, ointmeht or unguent; or
c) a sterile injectable liquid solution or suspension medium.
Whilst the modes of presentation and vehicle just listed represent those most likely to be employed, they do not necessarily exhaust the possibilities.
The compounds of this invention may preferably be administered in the form of tablets (particularly plain and sugar-coated tablets); of capsules (particularly gelatin capsules); of injectable solutions or suspensions; or of creams or ointments. For admi.nistration by a digestive or local route, the active principle may be incorporated with a vehicle made up of one or more excipients conventionally employed in such pharmaceutical compositions - for example, preferred excipients are talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, fatty substances of animal or vegetable origin, paraffin derivatives and glycols. Such compositions may also contain one or more wetting, dispersing or emulsifying agents, and/or preservatives.
The compositions of the invention may also be formulated for administration by the parenteral route. Injectable preparations of the compositions of the invention are preferably prepared extemporaneously by the addition of a sterile injectable solution to lyophilised erythromycin pyroglutamate.
Particularly preferred compositions of the invention includ compositions containing erythromycin pyroglutamate alone as active principle, as well as compositions containing other additional active ingredients - for example, compositions contain ing erythromycin pyroglutamate and erythromycin base; compositions containing erythromycin pyroglutamate and a colistin salt; and compositions containing erythromycin pyroglutamate, erythromycin base and a colistin salt. In compositions containing a colistin salt this ingredient is preferably present in the form of its sulphate.
Example of pharmaceutical compositions containing these additional active ingredients are set out hereinafter in the Formulations.
This invention will now be described, though only by way of illustration, with reference to the following Example and Formulations, which show preferred aspects of this invention.
Example
Preparation of Erythromycin pyroglatumate o
250 g of erythromycin base were suspended in 1550 cm of distilled water. The suspension was agitated, while a solution of 40 g of pyroglutamic acid in 1550 cm^ of distilled water was slowly introduced, so that the pH was always 7.1 or greater.
The pyroglutamic acid was added over a period of about one hour firty-five minutes.
The agitation was maintained for about one hour more and the solution obtained was then filtered on fritted glass. The filtrate and the waters from washing the filter were recovered, and 3.38 litres of an aqueous solution of erythromycin pyroglutamate were obtained.
The aqueous solution obtained was lyophilised and 271.94g of solvated erythromycin pyroglutamate containing 3.4% of water were recovered.
The product is present in the form of a white powder, soluble in water and melting at about 145-155°C.
Γαϊθ20 = -66.7° (c = 2% ethanol)
Bacteriological titre 880 γ/mg
Analysis: C^Hy^NgO·, θ = 863
Calculated: C% 58.45 H% 8.64 IU 3.24
Found: 58.3 8.4 3.0
Formulation 1
Gelatin capsules were prepared with the following composition:
2u erythromycin pyroglutamate 250 mg excipient (talc, starch, lactose) q.s.
for 1 gelatin capsule
Formulation 2
Injectable suspensions were prepared with the following composition:
erythromycin pyroglutamate {measured as erythromycin base) 500 mg colistin sulphate 2,400,000 units excipient q .s. to put into suspension extemporaneously, in 10 ml of water.
Formulation 3
Injectable suspensions were prepared with the following
Composition:
erythromycin base 50 mg erythromycin pyroglutamate (measured as erythromycin base) 50 mg mannitol 100 mg sodium mercurothiolactate 0. . 15 mg polysorbate 80 (sorbitan polyoxyethylene monooleate) 2 mg
colistin sulphate 240,000 units
The composition is intended to be put into suspension, extemporaneously, in 2 ml of water.
Claims (18)
1. Erythromycin pyroglutamate.
2. A process for preparing erythromycin pyroglutamate, in which pyroglutamic acid is reacted with erythromycin base.
3. A process as claimed in claim 2, in which the erythromycin base is present in a stoichiometric quantity or in excess, the pH of the reaction mixture being 7.1 or greater.
4. A process as claimed in claim 2 or claim 3, in which the reaction is carried out in distilled water, anhydrous acetone or methyl ethyl ketone saturated with water.
5. A process as claimed in any of claims 2 to 4, in which the desired erythromycin pyroglutamate is isolated by lyophilisation.
6. A process for preparing erythromycin pyroglutamate, in which a soluble salt of erythromycin and a soluble salt of pyroglutamic acid are reacted to give the desired erythromycin pyroglutamate.
7. A process as claimed in claim 6, in which the reaction is carried out in a medium consisting of water and an organic solvent not totally miscible with water.
8. A process as claimed in claim 7, in which an organic solvent is a lower alkyl acetate or a chlorinated organic solvent.
9. A process for the preparation of erythromycin pyroglutamate as claimed in any of claims 2 to 8, and substantially as described herein, with reference to the Example.
10. Erythromycin pyroglutamate, whenever prepared by a process as claimed in any of claims 2 to 9.
11. A pharmaceutical composition containing, as active principle, erythromycin pyroglutamate, either alone or in combination with other active ingredients, in association with a suitable pharmaceutical vehicle.
12. A pharmaceutical composition as claimed in claim 11, which contains erythromycin base as ah additional active ingredient
13. A pharmaceutical composition as claimed in claim 11 or claim 12, which contains colistin sulphate as an additional active ingredient.
14. A pharmaceutical composition as claimed in any of claims 11 to 13, in which the vehicle is made up ofone or more 10 of talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, fatty substances of animal or vegetable origin, paraffin derivatives and glycols.
15. A pharmaceutical composition as claimed inany of claims 11 to 14, which also contains one or more wetting, 15 dispersing or emulsifying agents and/or preservatives.
16. A pharmaceutical composition as claimed in any of claims 11 to 13, in which the vehicle is a sterile injectable solution.
17. A pharmaceutical composition as claimed in any of claims 11 to 16, and substantially as described herein, with reference
18. 20 to the Formulations.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR7423013A FR2302084A1 (en) | 1974-07-02 | 1974-07-02 | NEW ERYTHROMYCIN SALT, ITS PREPARATION PROCESS AND ITS APPLICATION AS A MEDICINAL PRODUCT |
Publications (2)
Publication Number | Publication Date |
---|---|
IE41628L IE41628L (en) | 1976-01-02 |
IE41628B1 true IE41628B1 (en) | 1980-02-13 |
Family
ID=9140790
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE147275A IE41628B1 (en) | 1974-07-02 | 1975-07-02 | New erythromycin salt process for preparing it and compositions incorporating it |
Country Status (11)
Country | Link |
---|---|
JP (1) | JPS5129217A (en) |
BE (1) | BE830842A (en) |
CA (1) | CA1025442A (en) |
CH (1) | CH599152A5 (en) |
DE (1) | DE2529538A1 (en) |
DK (1) | DK299375A (en) |
FR (1) | FR2302084A1 (en) |
GB (1) | GB1485210A (en) |
IE (1) | IE41628B1 (en) |
LU (1) | LU72866A1 (en) |
NL (1) | NL7507863A (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5633353A (en) * | 1979-08-20 | 1981-04-03 | Toray Ind Inc | Reeling-out method for thread |
ES2152322T3 (en) * | 1994-06-29 | 2001-02-01 | Meiji Seika Kaisha | COMPOSITION OF STAISTED COLISTINE SULPHATE. |
-
1974
- 1974-07-02 FR FR7423013A patent/FR2302084A1/en active Granted
-
1975
- 1975-06-30 BE BE157851A patent/BE830842A/en not_active IP Right Cessation
- 1975-06-30 CA CA230,434A patent/CA1025442A/en not_active Expired
- 1975-06-30 LU LU72866A patent/LU72866A1/xx unknown
- 1975-07-01 CH CH856875A patent/CH599152A5/xx not_active IP Right Cessation
- 1975-07-01 JP JP8055475A patent/JPS5129217A/en active Pending
- 1975-07-02 IE IE147275A patent/IE41628B1/en unknown
- 1975-07-02 DK DK299375A patent/DK299375A/en unknown
- 1975-07-02 DE DE19752529538 patent/DE2529538A1/en not_active Ceased
- 1975-07-02 NL NL7507863A patent/NL7507863A/en not_active Application Discontinuation
- 1975-07-02 GB GB2780975A patent/GB1485210A/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
CH599152A5 (en) | 1978-05-12 |
BE830842A (en) | 1975-12-30 |
IE41628L (en) | 1976-01-02 |
LU72866A1 (en) | 1976-04-13 |
DK299375A (en) | 1976-01-03 |
FR2302084B1 (en) | 1979-05-18 |
CA1025442A (en) | 1978-01-31 |
JPS5129217A (en) | 1976-03-12 |
DE2529538A1 (en) | 1976-01-22 |
FR2302084A1 (en) | 1976-09-24 |
GB1485210A (en) | 1977-09-08 |
NL7507863A (en) | 1976-01-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPS62215527A (en) | Alzheimer's sclerosis remedy | |
JPS59144779A (en) | (+)catechine salt | |
NL194240C (en) | Lincomycin and clindamycin analogues. | |
US3017323A (en) | Therapeutic compositions comprising polyhydric alcohol solutions of tetracycline-type antibiotics | |
JP2921124B2 (en) | Oxidized glutathione alkyl ester | |
US4110441A (en) | Gamma-l-glutamyl cholamine phosphate | |
US4772589A (en) | Etoposide solution in NMP | |
US3144387A (en) | Anti-inflammatory compositions | |
JPS6043360B2 (en) | Production method of new amino acid derivatives | |
IE41628B1 (en) | New erythromycin salt process for preparing it and compositions incorporating it | |
DE2941288A1 (en) | CYSTEIN DERIVATIVES | |
GB2577363A (en) | Liquid pharmaceutical composition for oral administration comprising paracetamol and codeine phosphate | |
US2841526A (en) | Fatty acid-resin adsorption product | |
US3250679A (en) | Penicillin derivative | |
US3459854A (en) | Tetracycline cyclohexyl sulphamate and process for preparation | |
US3998964A (en) | α-Amino-β-(N-benzylthiocarbamoylthio) propionic acid and therapeutic compositions | |
US4131678A (en) | Urapidil/furosemide compounds, compositions and use | |
JPS6163695A (en) | Purimycin salt, manufacture and medicinal composition | |
IL21955A (en) | Salts of fusidic acid and antibiotics of the tetracycline series | |
EP0431759B1 (en) | Process for the preparation of a ranitidine resin absorbate | |
US3000874A (en) | Sulfate salt of erythromycin monoester | |
US4005214A (en) | Water-soluble amoxicillin salts | |
US3013942A (en) | Therapeutic erythromycin ester compositions | |
JPS6119632B2 (en) | ||
GB2051818A (en) | Derivative of 1 ,25-dihydroxy-cholecalciferol |