NO304725B1 - Therapeutically applicable cream of the oil-in-water type containing potassium aluminum sulfate - Google Patents
Therapeutically applicable cream of the oil-in-water type containing potassium aluminum sulfate Download PDFInfo
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- NO304725B1 NO304725B1 NO924671A NO924689A NO304725B1 NO 304725 B1 NO304725 B1 NO 304725B1 NO 924671 A NO924671 A NO 924671A NO 924689 A NO924689 A NO 924689A NO 304725 B1 NO304725 B1 NO 304725B1
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- Prior art keywords
- cream
- oil
- weight
- water
- potassium aluminum
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- 239000006071 cream Substances 0.000 title claims description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims description 27
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 title claims description 9
- 238000002360 preparation method Methods 0.000 claims description 23
- 239000012071 phase Substances 0.000 claims description 15
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 14
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 claims description 12
- 239000008346 aqueous phase Substances 0.000 claims description 5
- 206010046996 Varicose vein Diseases 0.000 description 25
- 229940037003 alum Drugs 0.000 description 23
- 208000027185 varicose disease Diseases 0.000 description 18
- 239000000243 solution Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 230000006872 improvement Effects 0.000 description 12
- 239000003792 electrolyte Substances 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 7
- 210000002414 leg Anatomy 0.000 description 7
- 238000005185 salting out Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- -1 polyoxyethylene Polymers 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- 239000004166 Lanolin Substances 0.000 description 5
- 239000003995 emulsifying agent Substances 0.000 description 5
- 230000035876 healing Effects 0.000 description 5
- 235000019388 lanolin Nutrition 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 229940039717 lanolin Drugs 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 235000019271 petrolatum Nutrition 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 239000002280 amphoteric surfactant Substances 0.000 description 3
- 239000003945 anionic surfactant Substances 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- 239000003093 cationic surfactant Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 239000002736 nonionic surfactant Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000003883 ointment base Substances 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 150000003626 triacylglycerols Chemical class 0.000 description 3
- 230000036269 ulceration Effects 0.000 description 3
- 239000003871 white petrolatum Substances 0.000 description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
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- 229920001219 Polysorbate 40 Polymers 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229940030225 antihemorrhagics Drugs 0.000 description 2
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940117583 cocamine Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000002874 hemostatic agent Substances 0.000 description 2
- 239000010512 hydrogenated peanut oil Substances 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000019612 pigmentation Effects 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- CSHOPPGMNYULAD-UHFFFAOYSA-N 1-tridecoxytridecane Chemical compound CCCCCCCCCCCCCOCCCCCCCCCCCCC CSHOPPGMNYULAD-UHFFFAOYSA-N 0.000 description 1
- HMFKFHLTUCJZJO-OQUNMALSSA-N 2-[(2R)-2-[(2R,3R,4R)-3,4-bis(2-hydroxyethoxy)oxolan-2-yl]-2-(2-hydroxyethoxy)ethoxy]ethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOC[C@@H](OCCO)[C@H]1OC[C@@H](OCCO)[C@H]1OCCO HMFKFHLTUCJZJO-OQUNMALSSA-N 0.000 description 1
- MWEOKSUOWKDVIK-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOCCOCCOCCOCCOCCOCCOCCO MWEOKSUOWKDVIK-UHFFFAOYSA-N 0.000 description 1
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 description 1
- CTXGTHVAWRBISV-UHFFFAOYSA-N 2-hydroxyethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCO CTXGTHVAWRBISV-UHFFFAOYSA-N 0.000 description 1
- CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 206010017543 Fungal skin infection Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 206010052891 Skin bacterial infection Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004163 Spermaceti wax Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- SJLAFUFWXUJDDR-KTKRTIGZSA-N [3-[3-(2,3-dihydroxypropoxy)-2-hydroxypropoxy]-2-hydroxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)COCC(O)COCC(O)CO SJLAFUFWXUJDDR-KTKRTIGZSA-N 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- NTGGOTYRTOXKMQ-UHFFFAOYSA-K aluminum;potassium;phosphate Chemical compound [Al+3].[K+].[O-]P([O-])([O-])=O NTGGOTYRTOXKMQ-UHFFFAOYSA-K 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000021302 avocado oil Nutrition 0.000 description 1
- 239000008163 avocado oil Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- BUOSLGZEBFSUDD-BGPZCGNYSA-N bis[(1s,3s,4r,5r)-4-methoxycarbonyl-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 2,4-diphenylcyclobutane-1,3-dicarboxylate Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1C(C=2C=CC=CC=2)C(C(=O)O[C@@H]2[C@@H]([C@H]3CC[C@H](N3C)C2)C(=O)OC)C1C1=CC=CC=C1 BUOSLGZEBFSUDD-BGPZCGNYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 239000003916 calcium stearoyl-2-lactylate Substances 0.000 description 1
- OEUVSBXAMBLPES-UHFFFAOYSA-L calcium stearoyl-2-lactylate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O.CCCCCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O OEUVSBXAMBLPES-UHFFFAOYSA-L 0.000 description 1
- 235000010957 calcium stearoyl-2-lactylate Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
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- 238000006297 dehydration reaction Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- 208000028659 discharge Diseases 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 229940021013 electrolyte solution Drugs 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
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- 238000005189 flocculation Methods 0.000 description 1
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- 238000010438 heat treatment Methods 0.000 description 1
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- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
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- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 1
- 229940042472 mineral oil Drugs 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 230000002746 orthostatic effect Effects 0.000 description 1
- 239000008385 outer phase Substances 0.000 description 1
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- 229940032041 peg-8 laurate Drugs 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 208000001297 phlebitis Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
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- 230000002035 prolonged effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007632 sclerotherapy Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940045870 sodium palmitate Drugs 0.000 description 1
- IDXHDUOOTUFFOX-UHFFFAOYSA-M sodium;2-[2-hydroxyethyl-[2-(tetradecanoylamino)ethyl]amino]acetate Chemical compound [Na+].CCCCCCCCCCCCCC(=O)NCCN(CCO)CC([O-])=O IDXHDUOOTUFFOX-UHFFFAOYSA-M 0.000 description 1
- GGXKEBACDBNFAF-UHFFFAOYSA-M sodium;hexadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCC([O-])=O GGXKEBACDBNFAF-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
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- 210000000689 upper leg Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Foreliggende oppfinnelse angår et nytt, terapeutisk effektivt preparat, nærmere bestemt en kaliumaluminiumsulfat-inneholdende krem av typen olje-i-vann som er anvendelig for behandling av åreknuter. Kremen er kjennetegnet ved at oljefasen omfatter farmasøytisk akseptable lipidlignende salvebasiser og at vannfasen omfatter vann, cetyltrimetylammonium-bromid og/eller cetyltrimetylammoniumklorid. The present invention relates to a new, therapeutically effective preparation, more specifically a potassium aluminum sulphate-containing cream of the oil-in-water type which is useful for the treatment of varicose veins. The cream is characterized by the oil phase comprising pharmaceutically acceptable lipid-like ointment bases and the water phase comprising water, cetyltrimethylammonium bromide and/or cetyltrimethylammonium chloride.
Åreknuter er en sykdomstilstand som utvikles som en konsekvens av endringene i det venøse blodåresystem under huden og påvirker 15 til 17 % av den voksne befolkning. De viktigste symptomer i forbindelse med åreknuter er: Forlengede vener med et slynget mønster under huden på lår og legger, hvilke er godt synlige i ortostatisk stilling. Sekundære endringer er: Fortynning og brunaktig pigmentering av huden, omfattende opphovning, fibrose og en distal, ytre sårdannelse på benene. Varicose veins are a disease condition that develops as a consequence of the changes in the venous blood vessel system under the skin and affects 15 to 17% of the adult population. The most important symptoms in connection with varicose veins are: Elongated veins with a sinuous pattern under the skin on the thighs and calves, which are clearly visible in an orthostatic position. Secondary changes are: Thinning and brownish pigmentation of the skin, extensive swelling, fibrosis and a distal, external ulceration of the legs.
Angående komplikasjonene kan den ytre sårdannelse som utvikles etter fortynning av huden, og som til slutt utvides til åreknutene, være kilden til en sterk blødning. De akutte eller mindre akutte former av årebetennelse, såvel som tromboemboliske komplikasjoner, er hyppige. Sopp- eller bakteriell dermatitt forbundet med blodkarforstyrrelser kan også nevnes. Regarding the complications, the external ulceration that develops after thinning of the skin, and which eventually extends to the varicose veins, can be the source of heavy bleeding. The acute or less acute forms of phlebitis, as well as thromboembolic complications, are frequent. Fungal or bacterial dermatitis associated with blood vessel disorders may also be mentioned.
Åreknuter behandles på kirurgisk eller ikke-kirurgisk måte, eller ved medisinsk behandling. Den kirurgiske behandling består av avsperring og fjerning av åreknuten, såvel som defekte, perforerte vener. For å forhindre et tilbakefall er det viktigste element ved det kirurgiske inngrep en nøyaktig lokalisering og fullstendige fremskaffelse av legg-lårforbind-elsesstedet. Skleroterapi ved kompresjon som induserer en til-stoppelse og forlenget fibrose i de kollapsede vener, repre-senterer en overgang mellom kirurgiske og ikke-kirurgiske løsninger. Varicose veins are treated surgically or non-surgically, or by medical treatment. The surgical treatment consists of blocking and removing the varicose vein, as well as defective, perforated veins. In order to prevent a recurrence, the most important element of the surgical intervention is an accurate localization and complete procurement of the calf-femoral joint site. Compression sclerotherapy, which induces a blockage and prolonged fibrosis in the collapsed veins, represents a transition between surgical and non-surgical solutions.
En generell behandling som består av samtidig anvendelse av ikke-kirurgiske metoder er mest anvendelig i den tidlige fase av sykdommen før utviklingen av åreknuter, og for å forhindre sekundære skader. Den kan anvendes på eldre personer og på personer som ønsker å utsette operasjon, såvel som ved de tilfeller av en mild form for åreknuter uten lidelser. Denne type behandling inkluderer f.eks.: bruk av elastiske strømper og bandasjer sentralt på foten og på benet; eller å plassere benene høyt, en metode for å redusere venetrykket, noe som også er en fornuftig terapi. A general treatment consisting of the simultaneous application of non-surgical methods is most applicable in the early phase of the disease before the development of varicose veins, and to prevent secondary damage. It can be used on elderly people and on people who want to postpone surgery, as well as in cases of a mild form of varicose veins without suffering. This type of treatment includes, for example: the use of elastic stockings and bandages centrally on the foot and on the leg; or placing the legs high, a method of reducing venous pressure, which is also a sensible therapy.
Det er kun kjent noen få løsninger for medisinsk behandling av denne sykdomstilstand. En av de best kjente av disse er den topiske anvendelse av kaliumaluminiumsulfat som fører til en betydelig forbedring av de ubehagelige symptomer som ledsager åreknuter. Only a few solutions are known for the medical treatment of this disease state. One of the best known of these is the topical application of potassium aluminum sulfate which leads to a significant improvement in the unpleasant symptoms that accompany varicose veins.
Kaliumaluminiumsulfat (1:1:2) [A1K(S04)212H20], dvs. alun (USP XXII) er et materiale som lenge har vært anvendt terapeutisk. På grunn av materialets sterke astringerende og betydelige antiseptiske virkninger anvendes det i bred ut-strekning i fast form som et blodstillende middel (hemostatisk middel) og som et skyllemiddel i oppløsning [Martindale: The Extra Pharmacopoeia, 19. Ed. The Pharmaceutical Press, London Potassium aluminum sulfate (1:1:2) [A1K(SO4)212H20], i.e. alum (USP XXII) is a material that has long been used therapeutically. Due to the material's strong astringent and significant antiseptic effects, it is widely used in solid form as a hemostatic agent (hemostatic agent) and as a rinsing agent in solution [Martindale: The Extra Pharmacopoeia, 19th Ed. The Pharmaceutical Press, London
(1989)]. (1989)].
Når det anvendes topisk benyttes en oppløsning av 0,5 til 5 % alun som forskjellige hud- og slimhinnelotions, såvel som gurglemidler, skyllemidler og lignende. When used topically, a solution of 0.5 to 5% alum is used as various skin and mucous membrane lotions, as well as gargles, rinses and the like.
Preparater for behandling av åreknuter inneholdende kaliumaluminiumsulfat er kommersielt tilgjengelige fra Florin Company (Szeged, Ungarn) under varemerkene "Varikopax B<R>" og "Varikopax-super"". Disse preparater inneholder mer enn 10 % alun inkorporert i en kjent salvebasis. Deres anvendelse er komplisert fordi alun er til stede i disse preparater i form av et fast materiale (pulver) og ikke i en oppløsning, og derfor kan den aktive bestanddel ikke virke på hudoverflaten etter påføringen av pastaen uten at det foretas en etterbehandling. Ifølge de oppgitte instruksjoner for bruk av disse preparater må pastaen fortynnes med vann på hudoverflaten, noe som fører til dannelse av en oppløsning som sikrer den terapeutiske effekt. Preparations for the treatment of varicose veins containing potassium aluminum sulfate are commercially available from the Florin Company (Szeged, Hungary) under the trade names "Varikopax B<R>" and "Varikopax-super". These preparations contain more than 10% alum incorporated in a known ointment base. Their application is complicated because alum is present in these preparations in the form of a solid material (powder) and not in a solution, and therefore the active ingredient cannot act on the skin surface after the application of the paste without a post-treatment. instructions for the use of these preparations, the paste must be diluted with water on the skin surface, which leads to the formation of a solution that ensures the therapeutic effect.
Denne sistnevnte prosedyre er uvanlig ved en salve-terapi, den er ubekvem for pasienten og behandlingen gjøres ytterst komplisert ved denne anvendelse. This latter procedure is unusual for an ointment therapy, it is uncomfortable for the patient and the treatment is made extremely complicated by this application.
En viktig mangel ved preparatene angitt ovenfor består i at kun en del av det faste alun oppløses fra pastaen som påføres på hudoverflaten, og derfor er alunets biologiske An important shortcoming of the preparations indicated above is that only part of the solid alum dissolves from the paste that is applied to the skin surface, and therefore the alum's biological
tilgjengelighet ytterst lav. availability extremely low.
Ved inngnidning kan den fortynnede hud skades og en blødning kan induseres av alunpartiklene som utfelles fra pastaen. When rubbed in, the thinned skin can be damaged and a bleed can be induced by the alum particles that precipitate from the paste.
Målet for foreliggende oppfinnelse var å utvikle en krem inneholdende kaliumaluminiumsulfat som er lett å vaske bort med vann, som ikke besitter manglene til de kjente preparater og som inneholder kaliumaluminiumsulfat i en oppløst, og ikke i en fast form, hvorved virkningen direkte kan utøves uten noen etterbehandling, og på grunn av kremens mykhet blir behandlingen lett og enkel for pasienten. The aim of the present invention was to develop a cream containing potassium aluminum sulphate which is easy to wash off with water, which does not have the shortcomings of the known preparations and which contains potassium aluminum sulphate in a dissolved, and not in a solid form, whereby the effect can be directly exerted without any post-treatment, and due to the softness of the cream, the treatment is easy and simple for the patient.
Det viktigste problem ved å fremstille en emulsjon inneholdende en alunoppløsning er å finne et emulgeringsmiddel som sikrer stabiliteten av det dispergerte system i lang tid (dvs. flere år). Fra litteraturen er det kjent at sterke elektrolytter som alun, på grunn av deres utsaltningseffekt, berøver hydratlaget fra emulgeringsmidlet, noe som induserer flokkulering av de dispergerte partikler. The most important problem in producing an emulsion containing an alum solution is to find an emulsifier that ensures the stability of the dispersed system for a long time (ie several years). It is known from the literature that strong electrolytes such as alum, due to their salting-out effect, deprive the hydrate layer of the emulsifier, which induces flocculation of the dispersed particles.
Utsaltningsprosessen er basert på at de eksisterende vann/ionebindinger i elektrolyttoppløsninger er sterkere enn de opprinnelige vann/vannbindinger, og at vannets struktur brytes ved å forhindre dannelsen av hydrogenbindinger mellom ionene og de neste vannmolekyler [Emulsions and Emulsion Technology, Part I, utg. ved K. J. Lissant, Marcel Dekker INC., New York (1974)]. The salting-out process is based on the fact that the existing water/ion bonds in electrolyte solutions are stronger than the original water/water bonds, and that the structure of the water is broken by preventing the formation of hydrogen bonds between the ions and the next water molecules [Emulsions and Emulsion Technology, Part I, ed. by K.J. Lissant, Marcel Dekker INC., New York (1974)].
Elektrolytters utsaltningseffekt på nøytrale molekyler, slik som forskjellige overflateaktive midler, er definert ved lengden av ioneradien til utsaltningskomponenten, såvel som ved konsentrasjon av elektrolytten. The salting-out effect of electrolytes on neutral molecules, such as various surfactants, is defined by the length of the ionic radius of the salting-out component, as well as by the concentration of the electrolyte.
For å oppnå en nyttig virkning må den aluninneholdende krem anvendt for behandling av åreknuter fremstilles i en konsentrasjon som vesentlig overstiger elektrolyttkonsentra-sjonen i de kjente kosmetiske eller terapeutiske kremer. Alunets utsaltningseffekt må følgelig betraktes som mer viktig enn det som er vanlig ved fremstilling av kremer. In order to achieve a useful effect, the alum-containing cream used for the treatment of varicose veins must be prepared in a concentration which substantially exceeds the electrolyte concentration in the known cosmetic or therapeutic creams. The salting out effect of the alum must therefore be considered more important than is usual in the production of creams.
Under undersøkelsene utført ved foreliggende oppfinnelse med formålet å utvikle en stabil krem inneholdende alun, er grupper av ikke-ioniske, anioniske, kationiske og amfoteriske overflateaktive midler testet som emulgeringsmidler. De During the investigations carried out by the present invention with the aim of developing a stable cream containing alum, groups of non-ionic, anionic, cationic and amphoteric surfactants have been tested as emulsifiers. The
følgende materialer er således testet. the following materials have thus been tested.
Ikke-ioniske overflateaktive midler: glyserylmono-stearat, tetraglyserylmonooleat, sukrose-mono-, di- eller triacylat, PEG-8-laurat, PEG-400-monolaurat, polyoksyetylen-(8)monolaurat, polysorbat 40, sorbimakrogolpalmitat 300, polyoksyetylen( 20 )sorbitanmonopalmitat, PEG-1000 cetyleter,PEG-20 cetyleter, polyoksyetylen(20 )cetyleter, polyoksyetylen-(3)tridecyleter, polypropylenglykol(18)butyleter, polyoksy-propylen(18)butyleter og Poloxamer 401. Nonionic surfactants: glyceryl mono-stearate, tetraglyceryl monooleate, sucrose mono-, di- or triacylate, PEG-8 laurate, PEG-400 monolaurate, polyoxyethylene (8) monolaurate, polysorbate 40, sorbimacrogol palmitate 300, polyoxyethylene (20 ) sorbitan monopalmitate, PEG-1000 cetyl ether, PEG-20 cetyl ether, polyoxyethylene (20 ) cetyl ether, polyoxyethylene (3) tridecyl ether, polypropylene glycol (18) butyl ether, polyoxy-propylene (18) butyl ether and Poloxamer 401.
Anioniske overflateaktive midler: natriumpalmitat, kalsiumstearoyl-2-laktylat, natriumlaurylsulfat, dioktyl-natriumsulfosuccinat, og dietanolammoniumpolyoksyetylen(10)-oleyleterfosfat. Anionic surfactants: sodium palmitate, calcium stearoyl-2-lactylate, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, and diethanolammonium polyoxyethylene(10)-oleyl ether phosphate.
Kationiske overflateaktive midler: PEG-15 kokamin, cetyltrimetylammonium-bromid og -klorid (henholdsvis CTAB og Cationic surfactants: PEG-15 cocamine, cetyltrimethylammonium bromide and chloride (CTAB and
CTAC). CTAC).
Amfoteriske overflateaktive midler: 1,2-diacyl-L-fosfatidylkolin og myristoamfoacetat. Amphoteric surfactants: 1,2-diacyl-L-phosphatidylcholine and myristoamphoacetate.
Ved undersøkelse av stabiliteten av aluninneholdende emulsjoner, fremstilt ved anvendelse av de ovenfor angitte overflateaktive midler, er det påvist at det foreligger en uforenlighet mellom alun og de anioniske overflateaktive midler, og derfor er de overflateaktive midler av denne gruppe uegnede for fremstilling av dispersjoner. When examining the stability of alum-containing emulsions, prepared using the above-mentioned surfactants, it has been demonstrated that there is an incompatibility between alum and the anionic surfactants, and therefore the surfactants of this group are unsuitable for the preparation of dispersions.
Resultatene erholdt ved anvendelse av ikke-ioniske overflateaktive midler viste at dispersjoner kan fremstilles ved anvendelse av emulgeringsmidler av denne gruppe, men på grunn av alunets utsaltningseffekt foregikk en gradvis atskillelse av fasene i disse dispersjoner etter noen få ukers lagring. The results obtained using non-ionic surfactants showed that dispersions can be prepared using emulsifiers of this group, but due to the alum's salting-out effect, a gradual separation of the phases in these dispersions took place after a few weeks of storage.
Det samme fenomen er også observert med de undersøkte amfoteriske overflateaktive midler, såvel som med PEG-15-kokamin som tilhører gruppen av kationiske overflateaktive midler. The same phenomenon has also been observed with the investigated amphoteric surfactants, as well as with PEG-15-cocamine which belongs to the group of cationic surfactants.
Under stabilitetsundersøkelser utført på henholdsvis CTAB og CTAC, er det imidlertid overraskende funnet at emulsjoner inneholdende en alunoppløsning fremstilt ved anvendelse av CTAB eller CTAC, opprettholdt sin opprinnelige struktur selv etter to år, dvs. at det ikke foregikk noen dehydratiser- ing av det overf lateaktive middel i det således erholdte system. During stability studies carried out on CTAB and CTAC, respectively, it has surprisingly been found that emulsions containing an alum solution prepared using CTAB or CTAC maintained their original structure even after two years, i.e. that no dehydration of the surfactant took place agent in the system thus obtained.
Den ovenfor angitte erkjennelse er også overraskende fordi det i litteraturen foreligger flere angivelser av elektrolytters utsaltningseffekt overfor forskjellige overflateaktive midler, noe som er et fenomen som forekommer mellom en elektrolytt og nøytrale molekyler; det er imidlertid ikke funnet noen referanse som angår den resistens overfor elektrolytter som utvises av CTAB og CTAC, beskrevet i foreliggende patentsøknad. [Emulsion Science, utg. av P. Sherman, Academic Press, London og New York (1968)]. The above-mentioned realization is also surprising because in the literature there are several indications of the salting-out effect of electrolytes against various surface-active agents, which is a phenomenon that occurs between an electrolyte and neutral molecules; however, no reference has been found relating to the resistance to electrolytes exhibited by CTAB and CTAC, described in the present patent application. [Emulsion Science, ed. by P. Sherman, Academic Press, London and New York (1968)].
Ved hjelp av de ovenfor angitte overflateaktive midler, og ved anvendelse av noen farmasøytisk akseptable additiver, er en krem av typen olje-i-vann fremstilt. Verken fysiske eller kjemiske endringer er observert etter lagring av eksperimentpreparåtene i 2 år ved en isotermisk temperatur på henholdsvis 5 °C eller 25 °C. By means of the above-mentioned surfactants, and by using some pharmaceutically acceptable additives, an oil-in-water type cream is prepared. Neither physical nor chemical changes have been observed after storage of the experimental preparations for 2 years at an isothermal temperature of 5 °C or 25 °C respectively.
De således fremstilte kremer er myke og lette å på-føre på hudoverflaten. The creams produced in this way are soft and easy to apply to the skin surface.
Når eksperimentpreparatene fremstilt ved anvendelse av henholdsvis CTAB og CTAC ble underkastet grundige kliniske forsøk, ble det etter behandling observert både hos utepasienter og innepasienter at deres subjektive lidelser på grunn av de utvidete, middels alvorlige former av primære åreknuter i leggene ble moderert; de smertefulle, brennende og kløende følelser ble betydelig svekket. De objektive symptomer (tegn på omgivende inflammasjon, tilbøyelighet til ødemdann-else, utsondringsfenomener) viste en forbedring på tilnærmet 85 %. Det ble verken funnet ugunstige bivirkninger eller komplikasjoner i noen av disse tilfeller. På grunn av kremens mykhet og avkjølende virkning ble den lett akseptert av pasientene. When the experimental preparations prepared using CTAB and CTAC respectively were subjected to thorough clinical trials, after treatment it was observed both in outpatients and inpatients that their subjective disorders due to the enlarged, medium-severe forms of primary varicose veins in the legs were moderated; the painful, burning and itching sensations were significantly weakened. The objective symptoms (signs of surrounding inflammation, tendency to edema formation, secretion phenomena) showed an improvement of approximately 85%. Neither adverse side effects nor complications were found in any of these cases. Because of the cream's softness and cooling effect, it was easily accepted by the patients.
Basert på de ovenfor angitte resultater angår foreliggende oppfinnelse en ny, terapeutisk anvendelig krem av typen olje-i-vann, omfattende en vandig oppløsning av kalium-aluminiumfosfat som den vandige fase. Oljefasen inneholder farmasøytisk akseptable salvebasiser som: hydrokarboner, f.eks. mineralolje eller petrolatum; triglyserider, f.eks. kokosolje, palmeolje, kokossmør, avokadoolje, lakserolje, syntetiske fettsyreestere av glyserol (f.eks. Miglyol-810, -812, -818, -840, Dynamit Nobel AG, Troisdorf Oberlal, Tysk-land); hydrogenerte triglyserider, f.eks. hydrogenert peanøtt-olje; høymolekylære alkoholer, f.eks. laurylalkohol, myri-stylalkohol, cetylalkohol, stearylalkohol, cetylstearylalkohol, oktyldodekanol, oleylalkohol; lanolinalkohol; vokser, f.eks. bivoks, ullvoks, spermacettvoks; fettsyrer, f.eks. stearinsyre; etoksylerte triglyserider, f.eks. etoksylert lakserolje, eller en blanding derav. Based on the results stated above, the present invention relates to a new, therapeutically applicable cream of the oil-in-water type, comprising an aqueous solution of potassium aluminum phosphate as the aqueous phase. The oil phase contains pharmaceutically acceptable ointment bases such as: hydrocarbons, e.g. mineral oil or petrolatum; triglycerides, e.g. coconut oil, palm oil, coconut butter, avocado oil, castor oil, synthetic fatty acid esters of glycerol (eg, Miglyol-810, -812, -818, -840, Dynamit Nobel AG, Troisdorf Oberlal, Germany); hydrogenated triglycerides, e.g. hydrogenated peanut oil; high molecular weight alcohols, e.g. lauryl alcohol, myristylyl alcohol, cetyl alcohol, stearyl alcohol, cetylstearyl alcohol, octyldodecanol, oleyl alcohol; lanolin alcohol; growing, e.g. beeswax, wool wax, spermaceti wax; fatty acids, e.g. stearic acid; ethoxylated triglycerides, e.g. ethoxylated castor oil, or a mixture thereof.
Kremen ifølge foreliggende oppfinnelse inneholder fra 0,1 til 5,0 vekt% cetyltrimetylammoniumbromid og/eller cetyltrimetylammoniumklorid som emulgeringsmiddel. The cream according to the present invention contains from 0.1 to 5.0% by weight of cetyltrimethylammonium bromide and/or cetyltrimethylammonium chloride as an emulsifier.
Preparatet ifølge foreliggende oppfinnelse inneholder den vandige fase i en mengde fra 20 til 90 vekt%, fortrinnsvis fra 40 til 90 vekt%, beregnet i forhold til salven. The preparation according to the present invention contains the aqueous phase in an amount from 20 to 90% by weight, preferably from 40 to 90% by weight, calculated in relation to the ointment.
Den vandige fase inneholder fra 1 til 15 vekt%, fortrinnsvis fra 3 til 7 vekt% alun, uttrykt som A1K(S04)212H20 og 0 til 10 vekt% propylenglykol. The aqueous phase contains from 1 to 15% by weight, preferably from 3 to 7% by weight of alum, expressed as AlK(SO4)212H2O and 0 to 10% by weight of propylene glycol.
Kremen ifølge foreliggende oppfinnelse kan fremstilles ved oppløsning av alun i vann ved romtemperatur, hvilket danner salvens ytre fase, og oppløsning av cetyltrimetylammoniumbromid og/eller cetyltrimetylammoniumklorid i den således erholdte oppløsning, etterfulgt av blanding av propylenglykol i oppløsningen og oppvarming til 55-75 °C. Kompo-nentene i oljefasen blandes deretter og oppvarmes til 55-75 °C. De varme oljefaser og vannfaser kombineres i en kremblander og homogeniseres ved omrøring. The cream according to the present invention can be produced by dissolving alum in water at room temperature, which forms the outer phase of the ointment, and dissolving cetyltrimethylammonium bromide and/or cetyltrimethylammonium chloride in the thus obtained solution, followed by mixing propylene glycol in the solution and heating to 55-75 °C . The components in the oil phase are then mixed and heated to 55-75 °C. The hot oil phases and water phases are combined in a cream mixer and homogenized by stirring.
Etter blanding av de to faser fortsettes omrøringen inntil temperaturen i emulsjonen er sunket til 25-30 °C. Kremen som dannes etter avkjølingen fylles opp (suppleres) med vann for å justere dens sluttvekt. After mixing the two phases, stirring is continued until the temperature in the emulsion has dropped to 25-30 °C. The cream that forms after cooling is filled up (supplemented) with water to adjust its final weight.
Preparatet underkastes en gjentatt homogenisering og fylles deretter på hermetisk lukkede, elektrolyttresistente tuber eller beholdere. The preparation is subjected to repeated homogenization and then filled into hermetically sealed, electrolyte-resistant tubes or containers.
I overensstemmelse med denne fremgangsmåte kan det således fremstilles en stabil, aluninneholdende krem som besitter god biologisk tilgjengelighet og fordelaktige fysi-kalske egenskaper, ved anvendelse av vanlige anvendte farma-søytisk akseptable additiver. In accordance with this method, a stable, alum-containing cream can thus be produced which possesses good biological availability and advantageous physical properties, by using commonly used pharmaceutically acceptable additives.
Foreliggende oppfinnelse illustreres i detalj ved hjelp av de følgende eksempler. The present invention is illustrated in detail by means of the following examples.
Eksempel 1 Example 1
Kremen formuleres fra de ovenfor angitte bestanddeler på følgende måte. The cream is formulated from the above-mentioned ingredients in the following way.
Cetylstearylalkohol, etoksylert lakserolje, lanolinalkohol, oktyldodekanol og hvit petrolatum, veid og blandet i det ovenfor definerte forhold, oppvarmes til 60 °C. Alun og CTAC oppløses i vann ved romtemperatur og deretter oppvarmes oppløsningen til 62 °C. Begge faser kombineres i en kremblander og homogeniseres ved omrøring. Under omrøring avkjøles kremen til tilnærmet 30 °C og vekten suppleres med renset vann som angitt i formuleringen. Deretter homogeniseres kremen på nytt ved omrøring og fylles deretter på en elektrolyttresistent lagringsflaske. Cetyl stearyl alcohol, ethoxylated castor oil, lanolin alcohol, octyldodecanol and white petrolatum, weighed and mixed in the ratio defined above, are heated to 60°C. Alum and CTAC are dissolved in water at room temperature and then the solution is heated to 62 °C. Both phases are combined in a cream mixer and homogenized by stirring. While stirring, the cream is cooled to approximately 30 °C and the weight is supplemented with purified water as specified in the formulation. The cream is then re-homogenized by stirring and then filled into an electrolyte-resistant storage bottle.
Eksempel 2 Example 2
Kremen formuleres fra de ovenfor angitte bestanddeler på følgende måte. The cream is formulated from the above-mentioned ingredients in the following way.
Hvit petrolatum, cetylstearylalkohol og mineralolje, veid og blandet i det ovenfor definerte forhold, oppvarmes til 70 °C. White petrolatum, cetyl stearyl alcohol and mineral oil, weighed and mixed in the ratio defined above, are heated to 70 °C.
Alun og CTAB oppløses vann ved romtemperatur og opp-løsningen oppvarmes til 72 °C. Begge faser kombineres i en kremblander og homogeniseres ved omrøring. Under omrøring av-kjøles kremen til tilnærmet 30 "C og vekten suppleres med renset vann som angitt i formuleringen. Deretter homogeniseres kremen ved omrøring og fylles så på en elektrolyttresistent lagringsflaske. Alum and CTAB are dissolved in water at room temperature and the solution is heated to 72 °C. Both phases are combined in a cream mixer and homogenized by stirring. While stirring, the cream is cooled to approximately 30 °C and the weight is supplemented with purified water as indicated in the formulation. The cream is then homogenized by stirring and then filled into an electrolyte-resistant storage bottle.
Eksempel 3 Example 3
Kremen formuleres fra de ovenfor angitte bestanddeler på følgende måte. The cream is formulated from the above-mentioned ingredients in the following way.
Hvit petrolatum, mineralolje, lanolin, lanolinalkohol og bivoks, veid og blandet i det ovenfor definerte forhold, oppvarmes til 70 °C. Alun og CTAB oppløses i vann ved romtemperatur og oppløsningen oppvarmes til 72 °C. Begge faser kombineres i en kremblander og homogeniseres ved omrøring. White petrolatum, mineral oil, lanolin, lanolin alcohol and beeswax, weighed and mixed in the ratio defined above, are heated to 70 °C. Alum and CTAB are dissolved in water at room temperature and the solution is heated to 72 °C. Both phases are combined in a cream mixer and homogenized by stirring.
Under omrøring avkjøles kremen til tilnærmet 25 "C og vekten suppleres med demineralisert vann, som angitt i formuleringen. Deretter homogeniseres kremen ved omrøring og fylles så på elektrolyttresistente lagringsflasker. While stirring, the cream is cooled to approximately 25 "C and the weight is supplemented with demineralized water, as indicated in the formulation. The cream is then homogenized by stirring and then filled into electrolyte-resistant storage bottles.
Eksempel 4 Example 4
Kremen formuleres fra de ovenfor angitte bestanddeler på følgende måte. The cream is formulated from the above-mentioned ingredients in the following way.
Hydrogenert peanøttolje og cetylalkohol, veid og blandet i det ovenfor definerte forhold, oppvarmes til 55 °C. Alun, CTAC og CTAB oppløses i vann ved romtemperatur, propylenglykol tilsettes i den ovenfor definerte mengde og oppløsningen oppvarmes til 57 °C. Hydrogenated peanut oil and cetyl alcohol, weighed and mixed in the ratio defined above, are heated to 55 °C. Alum, CTAC and CTAB are dissolved in water at room temperature, propylene glycol is added in the amount defined above and the solution is heated to 57 °C.
Begge faser kombineres i en kremblander og homogeniseres ved omrøring. Under omrøring avkjøles kremen til tilnærmet 30 "C og vekten suppleres med renset vann som angitt i formuleringen. Both phases are combined in a cream mixer and homogenized by stirring. While stirring, the cream is cooled to approximately 30 °C and the weight is supplemented with purified water as indicated in the formulation.
Deretter homogeniseres kremen ved omrøring og fylles så på elektrolyttresistente flasker. The cream is then homogenised by stirring and then filled into electrolyte-resistant bottles.
Klinisk rapport for den åreknutehelbredende krem ifølge foreliggende oppfinnelse Clinical report for the varicose vein healing cream according to the present invention
Den ovenfor angitte krem ble klinisk testet, delvis på utepasienter, delvis på innepasienter. Primær åreknutedannelse i leggene ble behandlet med de helbredende preparater, først ved hjelp av den dobbelte hypotetiske metode og deretter ved hjelp av kremen inneholdende den kjente aktive bestanddel. Blant pasientene ble årebetennelsestilfeller, som er alvorlige tilstander på grunn av akutte inflammasjonssymptomer, ute-lukket . The above mentioned cream was clinically tested, partly on outpatients, partly on inpatients. Primary varicose veins in the calves were treated with the healing preparations, first by means of the double hypothetical method and then by means of the cream containing the known active ingredient. Among the patients, cases of varicose veins, which are serious conditions due to acute inflammation symptoms, were excluded.
Preparatene ble anvendt på 50 pasienter (den yngste 19 år, den eldste 76 år, gjennomsnitt 48,6 år) og disse tester viste at den åreknutehelbredende krem er egnet til både å redusere subjektive lidelser og til effektiv behandling av objektive symptomer. Positive rapporter ble mottatt vedrørende subjektive lidelser (den brennende, kløende følelse opphørte, smerten ble redusert og tretthetsfølelsen avtok) i hvert til-felle. Det ble observert forbedringer av objektive symptomer (redusert åreknutedannelse, redusert tendens til ødemer, redusert svelling, ytterligere forbedring av andre kosmetiske faktorer) på tilnærmet 85 %. The preparations were used on 50 patients (the youngest 19 years, the oldest 76 years, average 48.6 years) and these tests showed that the varicose vein healing cream is suitable for both reducing subjective disorders and for effective treatment of objective symptoms. Positive reports were received regarding subjective complaints (the burning, itching sensation ceased, the pain was reduced and the feeling of fatigue decreased) in each case. Improvements in objective symptoms (reduced varicose vein formation, reduced tendency to oedema, reduced swelling, further improvement of other cosmetic factors) of approximately 85% were observed.
På basis av alle disse resultater, og fordi det ikke ble observert noen bivirkninger eller komplikasjoner, kan preparatet anvendes regelmessig. On the basis of all these results, and because no side effects or complications were observed, the preparation can be used regularly.
Klinisk rapport for " Revena", åreknutehelbredende krem Clinical report for "Revena", varicose vein healing cream
Fra 1. september til 7. oktober 1991 ble det utført kliniske tester med "Revena", åreknutehelbredende krem, ved kirurgisk avdeling nr. 2, Semmelweis Medisinske Universitet, delvis på innepasienter, delvis på utepasienter. From 1 September to 7 October 1991, clinical tests were carried out with "Revena", varicose vein healing cream, at the Department of Surgery No. 2, Semmelweis Medical University, partly on inpatients, partly on outpatients.
Preparatet ble anvendt på 50 pasienter med primære åreknuter i leggene. Pasientenes gjennomsnittsalder var 48,6 år; den yngste var 19 år, den eldste var 76 år. 24 pasienter, av 36 kvinner og 14 menn, hadde åreknuter i begge legger. I disse tilfeller ble det utført behandling på den leggen som hadde de alvorligste endringer. The preparation was used on 50 patients with primary varicose veins in the legs. The patients' average age was 48.6 years; the youngest was 19, the oldest was 76. 24 patients, out of 36 women and 14 men, had varicose veins in both legs. In these cases, treatment was carried out on the leg with the most severe changes.
Graden av endringer ble klassifisert fra 1 til 4, fra de små isolerte endringer, gjennom omfattende åreknuter i store vener og opp til sykdommer som påvirket det totale over-flatevenesystem. The degree of changes was classified from 1 to 4, from the small isolated changes, through extensive varicose veins in large veins and up to diseases affecting the total superficial venous system.
Åreknutenes alvorlighetsgrad ble delt i tre grupper, fra utvidelse av vener innenfor huden gjennom moderat opp-svulmede veneslynger og opp til de betydelig forlengede og ut-videde åreknutetyper i underhuden. The severity of the varicose veins was divided into three groups, from dilation of veins within the skin through moderately swollen venous loops and up to the significantly elongated and enlarged varicose vein types in the subcutaneous tissue.
De mest typiske subjektive lidelser ble bedømt på basis av pasientens rapport. Blant disse er tretthet, svelling, brennende følelse og smerte også angitt i den opp-summerende tabell. Objektive symptomer som er sekundære endringer er også angitt i tabellen. The most typical subjective disorders were assessed on the basis of the patient's report. Among these, fatigue, swelling, burning sensation and pain are also indicated in the summary table. Objective symptoms that are secondary changes are also indicated in the table.
Klassifisering av inflammasjonssymptomer: Classification of inflammation symptoms:
0 = det foreligger ingen omgivende inflammasjon, 1 = moderate utsondringssymptomer, 2 = inflammasjon på et middels stadium. Tilfellene med alvorlige årebetennelsessykdommer ble elimi-nert. 0 = there is no surrounding inflammation, 1 = moderate discharge symptoms, 2 = inflammation at an intermediate stage. The cases with serious varicose veins were eliminated.
Indurasjon og pigmentering av huden er også indikert. Klassifisering av hudskader forårsaket av forstyrrelser i den tropiske mekanisme: 0 = ingen endring, 1 = atropisk, fortynnet hud, 2 = sårdannelse i huden. Induration and pigmentation of the skin is also indicated. Classification of skin damage caused by disturbances in the tropic mechanism: 0 = no change, 1 = atropic, thinned skin, 2 = ulceration of the skin.
Ved kontroll av de ovennevnte faktorer i løpet av én-måneds perioden ble det erfart meget gunstige resultater. Forbedring av objektive symptomer ble observert hos 42 pasienter; By controlling the above-mentioned factors during the one-month period, very favorable results were experienced. Improvement of objective symptoms was observed in 42 patients;
1 15 tilfeller var resultatet en avgjort forbedring, i 27 tilfeller ble det funnet moderate forbedringer angående sekundære symptomer. I 8 tilfeller ble det ikke observert objektive 1 In 15 cases the result was a decided improvement, in 27 cases moderate improvements were found regarding secondary symptoms. In 8 cases no objective was observed
resultater i den ovenfor angitte tidsperiode. Avgjorte forbedringer ble hovedsakelig observert i mer alvorlige tilfeller med sekundære endringer. Alle 50 pasienter rapporterte reduk-sjon av deres subjektive lidelser. I 26 tilfeller var forbed-ringen vesentlig, i 24 tilfeller moderat. (Både objektive og subjektive resultater ble klassifisert med tallene 0; 1; 2, med betydningen: 0 = ingen forbedring, 1=moderat forbedring, 2 = betydelig forbedring). results in the time period indicated above. Definite improvements were mainly observed in more severe cases with secondary changes. All 50 patients reported a reduction in their subjective complaints. In 26 cases the improvement was substantial, in 24 cases moderate. (Both objective and subjective results were classified with the numbers 0; 1; 2, meaning: 0 = no improvement, 1 = moderate improvement, 2 = significant improvement).
Det ble ikke i noen tilfeller observert skadelige bivirkninger eller ubehagelige erfaringer under anvendelse av kremen. (Det skal anmerkes at pasientene ble gitt råd om en fordelaktig diett, og under anvendelsestiden benyttet de også elastiske bandasjer). Resultatene stammer følgelig fra en sammensatt terapi, men uten anvendelse av andre adjuvans-produkter. In no case were harmful side effects or unpleasant experiences observed while using the cream. (It should be noted that the patients were advised on a beneficial diet, and during the application period they also used elastic bandages). The results therefore derive from a compound therapy, but without the use of other adjuvant products.
Claims (5)
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NO924671A NO304725B1 (en) | 1992-12-04 | 1992-12-04 | Therapeutically applicable cream of the oil-in-water type containing potassium aluminum sulfate |
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NO924671A NO304725B1 (en) | 1992-12-04 | 1992-12-04 | Therapeutically applicable cream of the oil-in-water type containing potassium aluminum sulfate |
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NO924689D0 NO924689D0 (en) | 1992-12-04 |
NO924689L NO924689L (en) | 1994-06-06 |
NO304725B1 true NO304725B1 (en) | 1999-02-08 |
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