CH512246A - Antibiotic heparinates for topical use - Google Patents
Antibiotic heparinates for topical useInfo
- Publication number
- CH512246A CH512246A CH326370A CH326370A CH512246A CH 512246 A CH512246 A CH 512246A CH 326370 A CH326370 A CH 326370A CH 326370 A CH326370 A CH 326370A CH 512246 A CH512246 A CH 512246A
- Authority
- CH
- Switzerland
- Prior art keywords
- antibiotic
- heparinate
- heparinates
- aqs
- anticoagulant
- Prior art date
Links
- 229920000669 heparin Polymers 0.000 title claims abstract description 17
- 230000003115 biocidal effect Effects 0.000 title claims abstract description 12
- 230000000699 topical effect Effects 0.000 title claims description 8
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 claims abstract description 8
- 239000003146 anticoagulant agent Substances 0.000 claims abstract description 7
- 229940127219 anticoagulant drug Drugs 0.000 claims abstract description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 6
- 108010040201 Polymyxins Proteins 0.000 claims abstract description 6
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 6
- 229930193140 Neomycin Natural products 0.000 claims abstract description 5
- 229960004927 neomycin Drugs 0.000 claims abstract description 5
- 230000002035 prolonged effect Effects 0.000 claims abstract description 5
- 229960000318 kanamycin Drugs 0.000 claims abstract description 4
- 229930027917 kanamycin Natural products 0.000 claims abstract description 4
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 claims abstract description 4
- 229930182823 kanamycin A Natural products 0.000 claims abstract description 4
- 229960005322 streptomycin Drugs 0.000 claims abstract description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims abstract 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 230000002429 anti-coagulating effect Effects 0.000 claims description 3
- 235000019441 ethanol Nutrition 0.000 claims description 3
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000012736 aqueous medium Substances 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 229960001008 heparin sodium Drugs 0.000 claims 1
- 239000012429 reaction media Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 206010034133 Pathogen resistance Diseases 0.000 abstract 1
- 230000014508 negative regulation of coagulation Effects 0.000 abstract 1
- 229910021653 sulphate ion Inorganic materials 0.000 abstract 1
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 4
- 229960002897 heparin Drugs 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 229940053050 neomycin sulfate Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Antibiotic heparinates which have prolonged anticoagulant and antibacterial activity against gram-negative and antibiotic-resistant strains when applied topically are prped. by combining an aqs. soln. of sodium heparinate of pH 8.8.5 with an aqs. soln. of polymyxin, streptomycin, neomycin or kanamycin sulphate having a pH of 5-6 and separating and purifying the resulting difficulty soluble antibiotic heparinate with a mixture of 50 ml. of ethanol and 1250 ml. of acetone for each 250 - 300 ml. of aqs. medium.
Description
Procédé de préparation d'un héparinate d'antibiotique à action anticoagulante,
antibactérienne prolongée pour application topique
La présente invention a pour objet un procédé pour la préparation des héparinates d'antibiotiques à action anticoagulante, antibactérienne prolongée pour application topique.
Le traitement local des affections de la peau représente la modalité normale d'intervention dans la médication des affections de cet organe.
Par rapport à leurs actions antibactérienne ou anticoagulante, on connaît un important nombre de substances médicamenteuses à application topique.
Souvent, ces substances utilisées dans certaines maladies de la peau ont une action limitée en raison des propriétés du tissu lésé.
Tel est le comportement des antibiotiques administrés de cette manière. La présence d'un antibiotique est insuffisante pour assurer une action efficace à un tissu à circulation locale altérée par différentes causes.
La présente invention résout ce problème en ajoutant à l'antibiotique l'effet d'une substance anticoagulante.
Le choix de l'antibiotique et de l'anticoagulant a été fait de manière à assurer l'action retardée de ces produits.
Ainsi, on a remarqué que l'héparine - un anticoagulant connu et largement utilisé tant pour le traitement parentéral que topique - donne dans certaines conditions de réaction des sels insolubles avec les antibiotiques de types largement employés (polymyxine, néomycine.
kanamycine, streptomycine).
Cette propriété des héparinates d'antibiotiques susmentionnés permet leur emploi dans les conditions les meilleures, pour l'application topique où sont présents des germes sensibles aux respectifs antibiotiques.
Par la réduction de la solubilité de deux substances - l'antibiotique et l'anticoagulant autrement fortement solubles - on réalise une action topique simultanée et prolongée.
Les héparinates présentent une efficacité bactéricide spécifique pour germes Gram négatifs ainsi que ceux résistant aux autres antibiotiques.
Les doses efficaces sont non irritantes.
Exemple!
On dissout 15g d'héparine à 100-llOU.I./mg dans 150 ml d'eau distillée - la solution obtenue a un pH compris entre 8 et 8,5.
Séparément on dissout 10 g de sulfate de polymyxine dans 100 ml d'eau distillée. La solution a un pH compris entre 5 et 5,6.
Dans la solution d'héparine on introduit en fil mince et en agitant pendant environ 30 mn la solution de polymyxine. On obtient un précipité blanc floconneux, le pH de la suspension étant compris entre 7 et 7,5.
Dans la suspension formée on ajoute sous agitation 50 ml d'alcool éthylique et 1250 ml d'acétone. On continue d'agiter pendant environ 30 mn et ensuite on filtre le précipité et on le sèche dans un courant d'air chaud à environ 40O C. Après le séchage on obtient 22 g de sel de l'héparine avec la polymyxine.
Exemple il
On dissout 10g d'héparine sodique à 100U.I./mg dans 100 ml d'eau distillée: la solution obtenue a un pH compris entre 8 et 8,5.
Séparément on dissout 10 g de sulfate de néomycine dans 100 ml d'eau distillée: la solution obtenue a un pH compris entre 5,5 et 6.
Dans la solution d'héparine on introduit en fil mince et sous agitation la solution de néomycine. On obtient un précipité blanc floconneux, le pH de la suspension étant compris entre 6,5 et 7,5.
Dans la suspension formée on ajoute 5 volumes d'alcool éthylique et on continue d'agiter pendant environ 30 mn.
On filtre ensuite le précipité et on le sèche dans un courant d'air chaud à environ 400 C. Après le séchage on obtient 15 g de sel de l'héparine avec la néomycine.
Exemple Ill
On procède comme dans l'exemple II. On utilise comme antibiotique la kanamycine.
Exemple IV
On procède comme dans l'exemple II. On utilise comme antibiotique la streptomycine.
Process for preparing an antibiotic heparinate with anticoagulant action,
prolonged antibacterial for topical application
The present invention relates to a process for the preparation of heparinates of antibiotics with anticoagulant, prolonged antibacterial action for topical application.
The local treatment of skin conditions represents the normal modality of intervention in the medication of affections of this organ.
With respect to their antibacterial or anticoagulant actions, a large number of medicinal substances for topical application are known.
Often these substances used in certain skin diseases have limited action due to the properties of the damaged tissue.
This is the behavior of antibiotics administered in this way. The presence of an antibiotic is insufficient to ensure an effective action on a tissue with local circulation impaired by various causes.
The present invention solves this problem by adding to the antibiotic the effect of an anticoagulant substance.
The choice of antibiotic and anticoagulant was made so as to ensure the delayed action of these products.
Thus, it has been observed that heparin - a known anticoagulant widely used both for parenteral and topical treatment - gives, under certain reaction conditions, insoluble salts with antibiotics of widely used types (polymyxin, neomycin.
kanamycin, streptomycin).
This property of the above-mentioned antibiotic heparinates allows their use under the best conditions, for topical application where germs sensitive to the respective antibiotics are present.
By reducing the solubility of two substances - the antibiotic and the otherwise highly soluble anticoagulant - a simultaneous and prolonged topical action is achieved.
Heparinates exhibit specific bactericidal efficacy for Gram-negative bacteria as well as those resistant to other antibiotics.
The effective doses are non-irritant.
Example!
15 g of heparin at 100-llOU.I./mg are dissolved in 150 ml of distilled water - the solution obtained has a pH between 8 and 8.5.
Separately, 10 g of polymyxin sulfate is dissolved in 100 ml of distilled water. The solution has a pH between 5 and 5.6.
The polymyxin solution is introduced in a thin thread and with stirring for about 30 minutes into the heparin solution. A white fluffy precipitate is obtained, the pH of the suspension being between 7 and 7.5.
50 ml of ethyl alcohol and 1250 ml of acetone are added to the suspension formed with stirring. Stirring is continued for about 30 min and then the precipitate is filtered off and dried in a stream of hot air at about 40 ° C. After drying, 22 g of heparin salt with polymyxin are obtained.
Example he
10 g of sodium heparin at 100 I.U./mg are dissolved in 100 ml of distilled water: the solution obtained has a pH of between 8 and 8.5.
Separately, 10 g of neomycin sulfate is dissolved in 100 ml of distilled water: the solution obtained has a pH of between 5.5 and 6.
The neomycin solution is introduced in a thin wire and with stirring into the heparin solution. A white fluffy precipitate is obtained, the pH of the suspension being between 6.5 and 7.5.
5 volumes of ethyl alcohol are added to the suspension formed and stirring is continued for approximately 30 min.
The precipitate is then filtered off and dried in a stream of hot air at approximately 400 ° C. After drying, 15 g of heparin salt with neomycin are obtained.
Example Ill
The procedure is as in Example II. Kanamycin is used as an antibiotic.
Example IV
The procedure is as in Example II. Streptomycin is used as an antibiotic.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH326370A CH512246A (en) | 1970-03-05 | 1970-03-05 | Antibiotic heparinates for topical use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH326370A CH512246A (en) | 1970-03-05 | 1970-03-05 | Antibiotic heparinates for topical use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH512246A true CH512246A (en) | 1971-09-15 |
Family
ID=4252191
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH326370A CH512246A (en) | 1970-03-05 | 1970-03-05 | Antibiotic heparinates for topical use |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH512246A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5668119A (en) * | 1996-02-22 | 1997-09-16 | Medenica; Rajko D. | Topical pharmaceutical containing heparin and method of treatment |
-
1970
- 1970-03-05 CH CH326370A patent/CH512246A/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5668119A (en) * | 1996-02-22 | 1997-09-16 | Medenica; Rajko D. | Topical pharmaceutical containing heparin and method of treatment |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |