CS269593B1 - Site preparation with antiphlogistic effect - Google Patents
Site preparation with antiphlogistic effect Download PDFInfo
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- CS269593B1 CS269593B1 CS884140A CS414088A CS269593B1 CS 269593 B1 CS269593 B1 CS 269593B1 CS 884140 A CS884140 A CS 884140A CS 414088 A CS414088 A CS 414088A CS 269593 B1 CS269593 B1 CS 269593B1
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- heparin
- parts
- weight
- beta
- escin
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- 238000002360 preparation method Methods 0.000 title claims description 3
- 230000001741 anti-phlogistic effect Effects 0.000 title description 2
- 229920000669 heparin Polymers 0.000 claims abstract description 18
- 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 15
- 229960002897 heparin Drugs 0.000 claims abstract description 14
- AXNVHPCVMSNXNP-IVKVKCDBSA-N (2s,3s,4s,5r,6r)-6-[[(3s,4s,4ar,6ar,6bs,8r,8ar,9r,10r,12as,14ar,14br)-9-acetyloxy-8-hydroxy-4,8a-bis(hydroxymethyl)-4,6a,6b,11,11,14b-hexamethyl-10-[(e)-2-methylbut-2-enoyl]oxy-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy]-4-hydroxy-3, Chemical compound O([C@@H]1[C@H](O[C@H]([C@@H]([C@H]1O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@]1(CO)C)C)(C)C[C@@H](O)[C@@]1(CO)[C@@H](OC(C)=O)[C@@H](C(C[C@H]14)(C)C)OC(=O)C(/C)=C/C)C(O)=O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O AXNVHPCVMSNXNP-IVKVKCDBSA-N 0.000 claims abstract description 13
- AXNVHPCVMSNXNP-GKTCLTPXSA-N Aescin Natural products O=C(O[C@H]1[C@@H](OC(=O)C)[C@]2(CO)[C@@H](O)C[C@@]3(C)[C@@]4(C)[C@@H]([C@]5(C)[C@H]([C@](CO)(C)[C@@H](O[C@@H]6[C@@H](O[C@H]7[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O7)[C@@H](O)[C@H](O[C@H]7[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O7)[C@@H](C(=O)O)O6)CC5)CC4)CC=C3[C@@H]2CC1(C)C)/C(=C/C)/C AXNVHPCVMSNXNP-GKTCLTPXSA-N 0.000 claims abstract description 13
- 229940093314 beta-escin Drugs 0.000 claims abstract description 13
- AXNVHPCVMSNXNP-BEJCRFBNSA-N beta-escin Natural products CC=C(/C)C(=O)O[C@H]1[C@H](OC(=O)C)[C@]2(CO)[C@H](O)C[C@@]3(C)C(=CC[C@@H]4[C@@]5(C)CC[C@H](O[C@H]6O[C@@H]([C@H](O[C@H]7O[C@H](CO)[C@@H](O)[C@H](O)[C@H]7O)[C@H](O)[C@@H]6O[C@@H]8O[C@H](CO)[C@@H](O)[C@H](O)[C@H]8O)C(=O)O)[C@](C)(CO)[C@@H]5CC[C@@]34C)[C@@H]2CC1(C)C AXNVHPCVMSNXNP-BEJCRFBNSA-N 0.000 claims abstract description 13
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 8
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 8
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 8
- 239000012049 topical pharmaceutical composition Substances 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 4
- 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 4
- 238000000034 method Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 230000008901 benefit Effects 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims 4
- OHJKXVLJWUPWQG-PNRHKHKDSA-N Heparinsodiumsalt Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](O)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O)[C@H](C(O)=O)O1 OHJKXVLJWUPWQG-PNRHKHKDSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 239000012620 biological material Substances 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 238000010348 incorporation Methods 0.000 claims 1
- 239000012266 salt solution Substances 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 238000003860 storage Methods 0.000 claims 1
- 238000004809 thin layer chromatography Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 230000036571 hydration Effects 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 241000157282 Aesculus Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 229920001499 Heparinoid Polymers 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 239000002554 heparinoid Substances 0.000 description 1
- 229940025770 heparinoids Drugs 0.000 description 1
- 235000010181 horse chestnut Nutrition 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Eiešenie sa týká topického přípravku vo formě gelu, kde rezorbciu účinných. . látok cez pokožku, beta-escínu a najma heparinu napomáhá vytvorenie okluzívneho filmu na pokožke pomocou gelotvornej látky, hydroxypropylcelulozy moiekulovej hmotnosti 100 000.The solution relates to a topical formulation in the form of a gel, where the resorption is effective. . substances through the skin, beta-escin and especially heparin aids in the formation of occlusive film on the skin using gel forming hydroxypropylcellulose weight 100,000.
Description
CS 259 593 B1 1EN 259 593 B1 1
Vynález sa týká topického přípravku s antiflogistickým účinkom v gelovej forměs obsahom beta-escínu a heparinu určeného najma na liečenie varikózneho syndromu, .achordb venózneho aparátu.BACKGROUND OF THE INVENTION The present invention relates to a topical anti-inflammatory agent in gel form containing beta-escin and heparin, especially for the treatment of varicose syndrome, venous apparatus.
Beta-eecín je známou účinnou látkou semien pagaštanu koňského, jedné sa o kyslytriterpenglykozid empirického vzorca C^^HgyOg^. Táto liečivá látka sa používá oddávnej minulosti v ludovom liečitelatve (A.Kukowa: Die Verwendung der Rosskaetanie"Aesculus hippocastanům" in der Medizin, Die Pharmazie, 9,(1), 44-46, 1954). Escínposobí proti abnormálnemu zvýšeniu permeability kapilár, tým priamo proti vzniku edé-mu, resp. k rýchlejšiemu hojeniu už vytvořených edémov (Ratschow M. Zuř Therapievon Permeabilitatstórungen bei Geffšsskrankheiten., Therapie der Gegenwart, 129, 1951).Beta-eecin is a known active ingredient of horse chestnut seeds, one of the acidtriterpenglycoside of the empirical formula C ^^HgyOgg.. This drug substance has been used for a long time in human therapy (A.Kukowa: Die Verwendung der Rosskaetanie "Aesculus hippocastan" in der Medizin, Die Pharmazie, 9, (1), 44-46, 1954). Essence acts against abnormal increase in capillary permeability, thereby directly counteracting edema, respectively. for faster healing of already formed edema (Ratschow M. Zuur Therapievon Permeabilitatstórungen bei Geffsskrankheiten., Therapie der Gegenwart, 129, 1951).
Druhou účinnou látkou předmětného vynálezu je heparin. Chemicky sa jedná o poly-mér zložený z dimérov, acetylovaného glukozamínu a kyseliny glukurónovej. Táto látkahrá velkú úlohu pri procese zrážania krvi a je látka tělu vlastná. Při transdermál-nom podaní pSsobl antiflogisticky a rozpúáta tromby a mikrotromby (Remingtone, Phar-maceutical Sciences, XIV, 834-835, 197O>. Spomínaným farmakologickým účinkom napomáháantiflogistickému, antiedematóznemu účinku beta-escínu najma v spomínaných indikáci-ách, kde sekundárné dochádza k poruche krvnej zrážanlivosti.The second active ingredient of the present invention is heparin. Chemically, it is a polymer composed of dimers, acetylated glucosamine and glucuronic acid. This substance plays a major role in the blood clotting process and is the substance of the body. In the transdermal administration of p-multiplex antiphlogistic and dissolving thrombi and microtrombi (Remington, Pharmaceutical Sciences, XIV, 834-835, 197O.). blood clotting disorder.
Kombinácia týchto dvoch účinných látok je dávno známa (Rotě Liste Ed.Cantor.Ays-burg,1987), avSak prináša aplikačné tažkosti z hladiska biologickéj dostupnosti. Akoje známe heparin je látkou vysokej molekulovej hmotnosti (nad 100 000), preto trans-dermálne vstrebávanie je obtiažne.The combination of these two active ingredients has long been known (Rote Liste Ed.Cantor.Asysburg, 1987), but has application difficulties in terms of bioavailability. As heparin is known to be a high molecular weight agent (above 100,000), transdermal absorption is therefore difficult.
Poměrně zložitým rieSením problému je Stiepenie (enzymatické) heparinu na tzv.heparinoidy s molekulovou hmotnostou medzi 10 000 až 20 000. V tomto případe je per-kutánne vstrebávanie a difúzia v tkánive podstatné ulahčená (Jakob,P.Fassbender,B.,Portschr.Med. 87, 893, 1969). Nevýhodou postupu je komplikovaná příprava účinnéj lát-ky s vysokým percentuálnym stupňom na d- a podhmotnostných fragmentov. Tento spfisobznačné predražuje hotovú liekovú formu. Výhodou riešenia rezorbcie účinných látok, najma heparinu je vytvorenie okluzívnehoobalu in šitu pomocou gelotvomej látky priamo na pokožke a tým po hydratácii stratůmcorneum dochádza k zvýšenému vstrebávaniu aktívnych látok.A relatively complex solution to the problem is the cleavage of (enzymatic) heparin to so-called heparinoids with a molecular weight of between 10,000 and 20,000. In this case, the percutaneous absorption and diffusion in the tissue is substantially facilitated (Jakob, P.Fassbender, B., Portschr. Med., 87, 893 (1969). A disadvantage of the process is the complicated preparation of the active substance with a high percentage of d- and sub-weight fragments. This distinctive price makes the finished pharmaceutical form more expensive. The advantage of the solution of the resorption of active substances, especially of heparin, is the formation of occlusal packaging in situ by means of a gel-forming substance directly on the skin and thus, upon hydration of the stratum corneum, there is an increased absorption of the active substances.
To, že hydratácia je podstatná pre vstrebávanie účinných látok, je známe už dáv-nejšie (Shelmire,J.B.: Arch.Dermatol., 82,24, 1960). Tento poznatok bol využívanýnajma u mastí s obsahom steroidov (McKenzie, A.W.,Stoughton,R.B.: Arch. Dermatol.,86,608, 1962) pre zvýšenie rezorbcie aktívnych látok.The fact that hydration is essential for the absorption of the active ingredients has been known for a long time (Shelmire, J.B .: Arch.Dermatol., 82, 24, 1960). This finding has been used in steroid-containing ointments (McKenzie, A.W., Stoughton, R.B .: Arch. Dermatol., 86,608, 1962) to enhance the resorption of the active ingredients.
Podstatou předloženého vynálezu je topický prípravok s antiflogistickým účinkomobsahujúci beta-escín a heparin, vyznačujúci sa tým, že obsahuje 0,5 hmotnostného die-lu beta-escínu, 5 000 medzinárodných jednotiek sodnej soli heparinu, 2,5 hmotnostnéhodielu hydroxypropylcelulózy s molekulovou hmotnostou 100 000 v. 1000 hmotnostných die-loch hotového gelu. Ďalej-podstatou vynálezu je nový poznatok, že správnou volbou ge-lotvornej látky, v tomto případe derivátom celulózy, je vytvořený okluzívny film napovrchu pokožky a tým napomáhá hydratácii podkožných partií a tým aj rezorbcii a vyč-šiemu účinku heparinu a beta-escínu z liekovej formy. Pravděpodobně mechanizmus účin-ku je taký, že zmes etanolu a vody pod okluzívnym obalom (etanol sa nemože odpariť) znáča pokožku, znižuje jej povrchové napatie a rozpúšta lipidickú bariéru. Týmto účinkomje ulahčená cesta pře vstrebanie hydrofilných látok ako ýe napr. heparin. Při klinických štúdióch sa ukázalo, že antiflogistické antiedenatózne účinky ge-lu vyhotoveného podlá predmetu předloženého vynálezu sú v porovnaní s gelom, ktoréhopomocná látka má okluzívne účinky, sú asi o 30 až 40 % vyššie. Lieková forma, ktorá jepredmetom vynálezu sa porovnávala s gelom, ktorý obsahoval beta-escín, biologicky štie-pený heparin a.polyakrylát ako gelotvomú látku (bchodná značka Reparil^-Madaus NSR).SUMMARY OF THE INVENTION The present invention provides a topical anti-inflammatory agent comprising beta-escin and heparin comprising 0.5 weight percent beta-escin, 5,000 international units of heparin sodium, 2.5 weight percent hydroxypropylcellulose having a molecular weight of 100,000 v. 1000 parts by weight of the finished gel. It is a further object of the present invention to provide an occlusive film on the surface of the skin by proper selection of the gelling agent, in this case a cellulose derivative, thereby assisting in the hydration of the subcutaneous parts and thereby resorbing and exerting the effect of heparin and beta-escin on the drug forms. Probably the mechanism of action is that the mixture of ethanol and water under the occlusive coating (ethanol can not evaporate) knows the skin, reduces its surface tension and dissolves the lipid barrier. This effect makes the route of absorption of hydrophilic substances such as heparin easier. In clinical trials, the anti-inflammatory antiedenatal effects of the gel of the present invention have been shown to be about 30-40% higher compared to the gel that has occlusive effects. The dosage form of the invention was compared with a gel containing beta-escin, biodegraded heparin and polyacrylate as a gelling agent (Reparil®-Madada NSR).
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS884140A CS269593B1 (en) | 1988-06-15 | 1988-06-15 | Site preparation with antiphlogistic effect |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS884140A CS269593B1 (en) | 1988-06-15 | 1988-06-15 | Site preparation with antiphlogistic effect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS414088A1 CS414088A1 (en) | 1989-09-12 |
| CS269593B1 true CS269593B1 (en) | 1990-04-11 |
Family
ID=5383480
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS884140A CS269593B1 (en) | 1988-06-15 | 1988-06-15 | Site preparation with antiphlogistic effect |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS269593B1 (en) |
-
1988
- 1988-06-15 CS CS884140A patent/CS269593B1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CS414088A1 (en) | 1989-09-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| IF00 | In force as of 2000-06-30 in czech republic | ||
| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20070615 |