EP1513501A2 - Simple and multiple emulsions for decontamination of an organism or surfaces - Google Patents
Simple and multiple emulsions for decontamination of an organism or surfacesInfo
- Publication number
- EP1513501A2 EP1513501A2 EP03756050A EP03756050A EP1513501A2 EP 1513501 A2 EP1513501 A2 EP 1513501A2 EP 03756050 A EP03756050 A EP 03756050A EP 03756050 A EP03756050 A EP 03756050A EP 1513501 A2 EP1513501 A2 EP 1513501A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- approximately
- aqueous phase
- organic phase
- extractant
- mass
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000000839 emulsion Substances 0.000 title claims abstract description 123
- 238000005202 decontamination Methods 0.000 title abstract description 3
- 230000003588 decontaminative effect Effects 0.000 title abstract description 3
- 239000012074 organic phase Substances 0.000 claims abstract description 67
- 231100000331 toxic Toxicity 0.000 claims abstract description 27
- 230000002588 toxic effect Effects 0.000 claims abstract description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- 230000002496 gastric effect Effects 0.000 claims abstract description 6
- 230000000699 topical effect Effects 0.000 claims abstract description 5
- 239000008280 blood Substances 0.000 claims abstract description 4
- 210000004369 blood Anatomy 0.000 claims abstract description 4
- 239000004033 plastic Substances 0.000 claims abstract description 3
- 239000008346 aqueous phase Substances 0.000 claims description 96
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 66
- 239000004094 surface-active agent Substances 0.000 claims description 57
- 239000002253 acid Substances 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- SWZDQOUHBYYPJD-UHFFFAOYSA-N tridodecylamine Chemical compound CCCCCCCCCCCCN(CCCCCCCCCCCC)CCCCCCCCCCCC SWZDQOUHBYYPJD-UHFFFAOYSA-N 0.000 claims description 21
- 239000012071 phase Substances 0.000 claims description 18
- 238000001784 detoxification Methods 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 14
- -1 organophosphates Chemical class 0.000 claims description 13
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 claims description 12
- 229940057995 liquid paraffin Drugs 0.000 claims description 12
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000003792 electrolyte Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- XTAZYLNFDRKIHJ-UHFFFAOYSA-N n,n-dioctyloctan-1-amine Chemical compound CCCCCCCCN(CCCCCCCC)CCCCCCCC XTAZYLNFDRKIHJ-UHFFFAOYSA-N 0.000 claims description 10
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 9
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 9
- 229920001577 copolymer Polymers 0.000 claims description 9
- 231100000566 intoxication Toxicity 0.000 claims description 9
- 230000035987 intoxication Effects 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000000129 anionic group Chemical group 0.000 claims description 8
- 150000002430 hydrocarbons Chemical class 0.000 claims description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 229920000768 polyamine Polymers 0.000 claims description 8
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 7
- 229940085262 cetyl dimethicone Drugs 0.000 claims description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 7
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 150000002334 glycols Chemical class 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 229960005489 paracetamol Drugs 0.000 claims description 6
- 229920001296 polysiloxane Polymers 0.000 claims description 6
- 150000003512 tertiary amines Chemical class 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 5
- 125000002091 cationic group Chemical group 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 5
- KUYLHALFMPOMKK-UHFFFAOYSA-N hydroxy-sulfanylidene-bis(2,4,4-trimethylpentyl)-$l^{5}-phosphane Chemical compound CC(C)(C)CC(C)CP(O)(=S)CC(C)CC(C)(C)C KUYLHALFMPOMKK-UHFFFAOYSA-N 0.000 claims description 5
- 230000007935 neutral effect Effects 0.000 claims description 5
- 239000007764 o/w emulsion Substances 0.000 claims description 5
- 235000000346 sugar Nutrition 0.000 claims description 5
- GBBSUAFBMRNDJC-MRXNPFEDSA-N (5R)-zopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-MRXNPFEDSA-N 0.000 claims description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 4
- 150000002191 fatty alcohols Chemical class 0.000 claims description 4
- 239000004310 lactic acid Substances 0.000 claims description 4
- 235000014655 lactic acid Nutrition 0.000 claims description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid group Chemical group C(CCC(=O)O)(=O)O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 4
- 229960000820 zopiclone Drugs 0.000 claims description 4
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 230000000536 complexating effect Effects 0.000 claims description 3
- 229940093915 gynecological organic acid Drugs 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 150000008163 sugars Chemical class 0.000 claims description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 2
- 229920002367 Polyisobutene Polymers 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- JOPOVCBBYLSVDA-UHFFFAOYSA-N chromium(6+) Chemical class [Cr+6] JOPOVCBBYLSVDA-UHFFFAOYSA-N 0.000 claims description 2
- 229960001484 edetic acid Drugs 0.000 claims description 2
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000001384 succinic acid Substances 0.000 claims description 2
- 150000003462 sulfoxides Chemical class 0.000 claims description 2
- RTFZIQFXMOVJSL-UHFFFAOYSA-N CCCCCCSP(CC)CC Chemical compound CCCCCCSP(CC)CC RTFZIQFXMOVJSL-UHFFFAOYSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 abstract description 3
- 239000002184 metal Substances 0.000 abstract description 3
- 239000012530 fluid Substances 0.000 abstract 1
- 238000007911 parenteral administration Methods 0.000 abstract 1
- 238000011200 topical administration Methods 0.000 abstract 1
- 238000000605 extraction Methods 0.000 description 29
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 12
- 229960001138 acetylsalicylic acid Drugs 0.000 description 10
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 10
- 231100000167 toxic agent Toxicity 0.000 description 8
- 239000003440 toxic substance Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 239000007762 w/o emulsion Substances 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 101100514056 Rhodobacter capsulatus modD gene Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 240000000736 Amomum maximum Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- RCDRLKFSBNGVHE-UHFFFAOYSA-N CCCCCC(CC)(CC)P(O)=S Chemical compound CCCCCC(CC)(CC)P(O)=S RCDRLKFSBNGVHE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 208000003870 Drug Overdose Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000002879 Lewis base Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010058667 Oral toxicity Diseases 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
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 229940068372 acetyl salicylate Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 231100001133 acute intoxication condition Toxicity 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000019621 digestibility Nutrition 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 231100000725 drug overdose Toxicity 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920006007 hydrogenated polyisobutylene Polymers 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003295 industrial effluent Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000007527 lewis bases Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 231100000418 oral toxicity Toxicity 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000002957 persistent organic pollutant Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/113—Multiple emulsions, e.g. oil-in-water-in-oil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the subject of the invention is new simple water-in-oil emulsions, or multiple water-in-oil-in-water emulsions, and their use for detoxifying the body or surfaces.
- Acute intoxication represents, at the start of this millennium, one of the main causes of hospitalization in developed countries and death of individuals under the age of thirty in developing countries.
- the invention makes it possible to provide an original and effective alternative in the essential treatments intended for industrial, military emergencies, hospital, domestic and environmental.
- the invention aims to allow the treatment of oral poisoning which originates from the ingestion of pharmaceutical and non-pharmaceutical products, but also skin intoxication of domestic, industrial or military origin.
- the present invention aims to use very stable emulsions due to the presence in these emulsions of polymeric surfactants.
- the present invention relates to the use of single or multiple emulsions comprising in their organic phase one or more extracting compounds capable, when said emulsions are brought into contact with a medium, also designated external medium, either biological such as gastric liquid, skin or blood, either artificial or metallic or plastic surfaces, to extract from said medium specific toxic molecules capable of binding to said or said extractants, for the preparation of pharmaceutical compositions intended for the prevention or treatment of intoxication by oral, topical or parenteral, or for detoxifying surfaces by simple application to the aforementioned surfaces.
- a medium also designated external medium, either biological such as gastric liquid, skin or blood, either artificial or metallic or plastic surfaces
- the present invention relates to the use as mentioned above, of simple water in oil emulsions, or multiple water in hujle in water emulsions, the internal aqueous phase of which comprises one or more de-extracting compounds, trapping the toxic molecules extracted from the external medium .
- extracting compound is meant a molecule which will react chemically with the complex formed by the toxic molecule and the extractant, which on the one hand makes it possible to regenerate the extractant, and on the other hand, to trap the molecule toxic.
- the present invention also relates to the abovementioned use, characterized in that the extractant is chosen from:
- - amino derivatives such as primary, secondary or tertiary amines or quaternary ammonium salts, comprising one or more carbon chains each comprising around 1 to 18 carbon atoms, in particular trioctylamine or trilaurylamine, when the toxic molecule to be eliminated has an acid or anionic character,
- organic acids such as organophosphorus acids, thiophosphorus acids, carboxylic acids, comprising one or more carbon chains each comprising from approximately 1 to 18 carbon atoms, when the toxic molecule to be eliminated has a basic or cationic character
- the solvating molecules such as alcohols, organophosphates, phosphine oxides, organosulfides or sulfoxides, comprising one or more carbon chains each comprising about 1 to 18 carbon atoms, when the toxic molecule to be eliminated has a neutral character.
- molecule having an acid character designates in the broad sense a - Lewis acid (electron acceptor) such as a weak acid, in particular acetic acid, lactic acid, citric acid, acetylsalicylic acid or hydrocyanic acid.
- a - Lewis acid electron acceptor
- molecule having an anionic character designates an aqueous anion such as for example cyanide, fluoride or chloride ions, or anionic metal complexes such as for example FeC-U " or AuCLf-
- molecule having a basic character designates in the broad sense a Lewis base (electron donor) having for example a nitrogen atom (protonable) such as Toxin, urea, ammonia, quinine or amphetamines, or having a sulfur atom (protonable) such as for example the sulfide ion or the sulfite ion.
- molecule having a cationic character designates an aqueous cation such as for example the ammonium ion or the metal cations.
- molecule having a neutral character designates a molecule having no marked electron exchange properties, such as for example alcohols (ethanol), ketones, ethers, paracetamol, etc.
- a preferred organophosphorus acid, among the extractants, is di-2-ethylhexylphosphoric acid.
- octanol or decanol are preferably used as extractants.
- the present invention relates to the use as defined above, characterized in that the deextractant is chosen from: - bases such as NaOH, KOH, Na 2 CO 3 , when the toxic molecule to be eliminated has an acid or anionic character,
- oxidoreductive or complexing character such as chromium (VI) salts, thiourea, ethylene diamine tetracetic acid, chlorinated or fluorinated derivatives, ascorbic acid, when the toxic molecule to be eliminated has a neutral character.
- compounds with an oxidoreducing or complexing character designates compounds capable of reducing or oxidizing the toxic agent or of forming with it a lipophobic complex.
- the invention relates to the use of simple water-in-oil emulsions comprising:
- One or more extractants as defined above, the mass fraction of the extractant (s) relative to the organic phase being between approximately 0.1 and approximately 20%,
- One or more ether-bonded lipophilic surfactants such as al-kyldimethicone copolyols, or amine-bonded surfactants such as long chain condensed polyamines, or sorbitan or glycol esters, the mass fraction of the lipophilic surfactant (s) relative to the organic phase being between approximately 0.5 and approximately 20%,
- hydrocarbons such as liquid paraffins, perhydrosqualene or silicones or synthetic esters
- an internal aqueous phase containing one or more deextractants as defined above, and optionally an additive such as an electrolyte or a sugar, the mass ratio of the internal aqueous phase relative to the emulsion being between approximately 1 and about 80%, preferably between about 20% and about 70%.
- the invention relates to the use of multiple water-in-oil-in-water emulsions comprising: an external aqueous phase containing one or more hydrophilic surfactants with ether bond such as copolymers of ethylene oxide and propylene oxide, oxyethylenated fatty alcohols, or hydrophilic surfactants with ester bond such as polyoxyethylenated sorbitan esters , the mass fraction of these surfactants relative to the external aqueous phase being between approximately 0.1 and approximately 10%.
- hydrophilic surfactants with ether bond such as copolymers of ethylene oxide and propylene oxide, oxyethylenated fatty alcohols, or hydrophilic surfactants with ester bond such as polyoxyethylenated sorbitan esters
- One or more extractants as defined above, the mass fraction of the extractant (s) relative to the organic phase being between approximately 0.1 and approximately 20%,
- one or more lipophilic surfactants with ether bond such as alkyldimethicone copolyols, or with amino bond such as condensed polyamines with long chains, or sorbitan or glycol esters, the mass fraction of the lipophilic surfactant (s) relative to the phase organic being between approximately 0.5 and approximately 20%,
- hydrocarbons such as liquid paraffins, perhydrosqualene or silicones or synthetic esters
- the invention relates to the use as mentioned above, of single or multiple emulsions, for the detoxification of acid molecules, such as acetylsalicylic acid, characterized in that the extractant is a tertiary amine, in particular trioctylamine or trilaurylamine, and in that the deextractant is sodium hydroxide NaOH.
- the invention relates to the use as mentioned above, of simple water-in-oil emulsions, for the detoxification of acid molecules, such as acetylsalicylic acid, comprising:
- Cetyldimethicone copolyol as lipophilic surfactant at a rate of approximately 1 to approximately 10% by mass relative to the external organic phase
- an internal aqueous phase containing, as deextractant, sodium hydroxide, at a concentration such that the pH is greater than or equal to 13, the mass ratio between the aqueous phase and the total emulsion being between approximately 10% and approximately 70%, and preferably equal to about 50%.
- the invention relates to the use as mentioned above, of multiple water-in-oil-in-water emulsions, for the detoxification of acid molecules, such as acetylsalicylic acid, comprising:
- Cetyldimethicone copolyol as lipophilic surfactant at a rate of approximately 1 to approximately 10% by mass relative to the total mass of the organic phase,
- an internal aqueous phase containing, assupplementaryextractant, soda, at a concentration such that the pH is greater than or equal to 13, and magnesium sulfate, from about 2 to about 6% 'by weight relative to the total mass of the internal aqueous phase, the mass ratio between the internal aqueous phase and the organic phase being between approximately 25% and approximately 200%, and preferably equal to approximately 100%, and the mass ratio between the phase external aqueous and the primary single emulsion being between approximately 10% and approximately 90%, and preferably equal to approximately 25%.
- the invention relates to the use as mentioned above, of single or multiple emulsions, for the detoxification of -composites of very weak acid-base character, such as paracetamol, characterized in that the extractant used is a long-chain alcohol, in particular octanol, and in that the deextractant is NaOH.
- the invention relates to the use as mentioned above, of simple water in oil emulsions comprising:
- a polyamine condensed on succinic acid substituted with a polyisobutene chain such as ECA 4360, as lipophilic surfactant, in a proportion of approximately 1 to approximately 10% by mass relative to the external organic phase ,
- an internal aqueous phase containing, as a de-extractant, sodium hydroxide at a concentration such that the pH is greater than 13, the mass ratio between the aqueous phase and the total emulsion being between approximately 10% and approximately 70%, and preferably equal to about 50%.
- the invention relates to the use as mentioned above, of single or multiple emulsions, for the detoxification of compounds such as zopiclone ND , characterized in that the extractant used is an acid long-chain organothiophosphorus, in particular di-ethylhexyl-monothiophosphinic acid (Cyanex 302), and in that the deextractant is hydrochloric acid.
- the extractant used is an acid long-chain organothiophosphorus, in particular di-ethylhexyl-monothiophosphinic acid (Cyanex 302), and in that the deextractant is hydrochloric acid.
- the invention relates to the use as mentioned above, of simple water in oil emulsions comprising:
- ECA 4360 as lipophilic surfactant, at a rate of approximately 1 to approximately 10% by mass relative to the organic phase
- the present invention relates more particularly to the use of single or multiple emulsions as defined above, for the preparation of compositions intended for the decontamination of surfaces.
- the present invention more particularly relates to the use of single or multiple emulsions as defined above, for the preparation of pharmaceutical compositions intended for the prevention or treatment of intoxication by oral, topical or parenteral route.
- the present invention also relates to the use of single or multiple emulsions as defined above, for the preparation of medical devices intended for the prevention or treatment of intoxication by oral, topical or parenteral route.
- the present invention also relates to a pharmaceutical composition characterized in that it comprises a single or multiple emulsion as defined above, where appropriate in combination with a pharmaceutically acceptable vehicle.
- An advantageous pharmaceutical composition according to the invention is characterized in that it is in a form which can be administered by the oral route, single or repeated, in particular at a rate of approximately 10 to approximately 500 g.
- An advantageous pharmaceutical composition according to the invention is characterized in that it is in a form which can be administered topically, in particular at a rate of approximately 2 to approximately 50 mg / cm 2 of skin.
- An advantageous pharmaceutical composition according to the invention is characterized in that it is in a form which can be used for the parenteral route by an extracorporeal circulation, in particular at a rate of approximately 500 to approximately 1000 g.
- the present invention also relates to any multiple water-in-oil-in-water emulsion comprising in its organic phase one or more extracting compounds as defined above.
- the invention relates to any multiple emulsion as defined above, comprising in its organic phase one or more lipophilic surfactants as defined above.
- An advantageous multiple emulsion of the present invention comprises in its internal aqueous phase one or more deextracting compounds as defined above, and optional additives such as electrolytes or sugars.
- the preferred electrolytes are sodium chloride or magnesium sulfate.
- the preferred sugars are glucose or sucrose.
- An advantageous multiple emulsion of the present invention comprises in its external aqueous phase one or more hydrophilic surfactants as defined above.
- an external aqueous phase containing one or more hydrophilic ether-surfactants such as copolymers of ethylene oxide and propylene oxide, oxyethylenated fatty alcohols, or hydrophilic surfactants with ester bond such as polyoxyethylenated sorbitan esters , the mass fraction of these surfactants relative to the external aqueous phase being between approximately 0.1 and approximately 10%.
- hydrophilic ether-surfactants such as copolymers of ethylene oxide and propylene oxide, oxyethylenated fatty alcohols, or hydrophilic surfactants with ester bond such as polyoxyethylenated sorbitan esters
- One or more extractants as defined above, the mass fraction of the extractant (s) relative to the organic phase being between approximately 0.1 and approximately 20%,
- one or more lipophilic surfactants with ether bond such as alkyldimethicone copolyols, or with amino bond such as condensed polyamines with long chains, or sorbitan or glycol esters, the mass fraction of the lipophilic surfactant (s) relative to the phase organic being between approximately 0.5 and approximately 20%,
- hydrocarbons such as liquid paraffins, perhydrosqualene or silicones or synthetic esters
- the present invention also relates to a multiple emulsion as defined above, for the detoxification of acid molecules, such as acetylsalicylic acid, comprising:
- Cetyldimethicone copolyol as lipophilic surfactant at a rate of approximately 1 to approximately 10% by mass relative to the total mass of the organic phase,
- an internal aqueous phase containing, as a de-extractant, sodium hydroxide, at a concentration such that the pH is greater than or equal to 13, and magnesium sulphate, at a rate of approximately 2 to approximately 6% by mass relative to total mass of the internal aqueous phase, the mass ratio between the internal aqueous phase and the organic phase being between approximately 25% and approximately 200%, and preferably equal to approximately 100%, and the mass ratio between the external aqueous phase and the primary single emulsion being between approximately 10% and approximately 90%, and preferably equal to approximately 25%.
- the principle of the extraction of toxic molecules by an emulsified system (water in oil emulsion or water in oil in water emulsion) consists of:
- system I a simple water in oil emulsion
- system II a multiple water in oil in water emulsion
- a simple water-in-oil emulsion is prepared.
- This simple emulsion is stabilized by a lipophilic surfactant of low HLB (Hydrophilic / Lipophilic Balance) and contains fine droplets of internal aqueous phase with a diameter of 0.5 to 1 ⁇ m. It is presented as a relatively viscous milk.
- HLB Hydrophilic / Lipophilic Balance
- the toxic compound will pass through the organic solution to be collected and trapped in the droplets of internal aqueous phase.
- the originality and the efficiency of the process of the present invention are based on two particularly important aspects: the presence in the organic solution of a molecule (transporter or extractant) capable of helping the transport of the toxic compound in this phase and the presence in the internal aqueous phase of a trapping agent (de-extractant) which destroys the toxic-transporter complex and reacts with the latter to transform it into a very lipophobic species.
- a trapping agent de-extractant
- Acetylsalicylic acid will be denoted HA for the sake of simplification.
- the transporter is a long chain tertiary amine (R 3 N), a molecule with a weak basic character, which is very slightly soluble in water.
- the R 3 .NHA molecule is much more lipophilic than HA and therefore facilitates its solubilization in the organic phase.
- the trapping agent introduced into the internal aqueous phase is sodium hydroxide.
- the following chemical reaction takes place:
- Such a chemical system is also valid for other toxic molecules with an acidic character.
- organic acids such as lactic acid, ascorbic acid or citric acid
- mineral acids such as hydrochloric acid, nitric acid.
- sulfuric acid, hydrofluoric acid or hydrocyanic acid such as sulfuric acid, hydrofluoric acid or hydrocyanic acid.
- Primary, secondary and tertiary amines can be used as the carrier, provided they have one or more long carbon chains (to minimize their solubility in water). However, tertiary amines are the most effective because they are the most basic.
- the internal aqueous solution is a basic solution, consisting of a strong base like soda or potash or a weak base like sodium carbonate or potassium carbonate.
- strong bases are the most effective.
- trioctylamine C 8 H 1 ) 3 N or trilaurylamine (C 12 H 25 ) 3 N
- emulsions are prepared containing the following components:
- NaOH of different concentrations 50% (thereafter, all percentages represent mass ratios)
- TLA trilaurylamine
- the optimum content of the surfactant is therefore of the order of 3 to 5% of Abil.
- the following emulsions, containing trioctylamine (TOA) are prepared:
- composition of the emulsion prepared is as follows Dodecane: 47.1% TOA: 0.9% ABIL: 2% NaOH 0.1 mol.L "1 : 50% The extraction percentages obtained are as follows
- Arlatone F127G copolymer of ethylene oxide and propylene oxide
- the primary emulsion is prepared by heating the internal aqueous phase and the organic phase to 70-80 ° C using a water bath.
- the aqueous phase is incorporated into the oily phase with vigorous stirring at 3000 rpm using a Rayneri centripetal turbine for 30 minutes.
- the primary emulsion is slowly introduced into the external aqueous phase.
- This second emulsification is carried out by the same turbine with stirring of 500 rpm.
- the duration of agitation depends on the formulation and can vary from 5 to 45 minutes.
- solvating transporter for very weak acid-base toxic molecules (alcohol, glycol; paracetamol for example), a solvating transporter and an internal aqueous phase capable of reacting with the toxic agent to trap it in a lipophobic form (oxidant, strong base) will be considered. ..).
- Symmetrical systems are envisaged for extracting toxic substances of a basic nature by using as carrier a acid organic molecule (organophosphorus acid, carboxylic acid) very poorly soluble in water; the internal aqueous solution will be an acid solution.
- a acid organic molecule organic molecule (organophosphorus acid, carboxylic acid) very poorly soluble in water; the internal aqueous solution will be an acid solution.
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Abstract
Description
EMULSIONS SIMPLES ET MULTIPLES DESTINÉES À LA DÉTOXICATION DE L'ORGANISME OU DE SURFACES SINGLE AND MULTIPLE EMULSIONS FOR THE DETOXICATION OF THE ORGANISM OR SURFACES
L'invention a pour objet de nouvelles emulsions simples eau dans huile, ou multiples eau dans huile dans eau, et leur utilisation pour la détoxication de l'organisme ou de surfaces.The subject of the invention is new simple water-in-oil emulsions, or multiple water-in-oil-in-water emulsions, and their use for detoxifying the body or surfaces.
Les intoxications aiguës représentent, en ce début de millénaire, l'une des premières causes d'hospitalisation dans les pays développés et de mort d'individus de moins de trente ans dans les pays en voie de développement.Acute intoxication represents, at the start of this millennium, one of the main causes of hospitalization in developed countries and death of individuals under the age of thirty in developing countries.
Le traitement des intoxications orales est souvent très délicat à mettre en œuvre, car il est généralement difficile d'obtenir l'historique de l'intoxication par le patient lui- même. Le clinicien doit essentiellement porter son attention sur les symptômes pour pouvoir identifier le composé toxique ingéré et ainsi établir le traitement adéquat. Ce dernier dépendra essentiellement de la nature de la (ou des) molécule(s) toxique(s), du sujet, de l'heure d'ingestion, de la gravité de l'intoxication et des signes cliniques.The treatment of oral intoxication is often very difficult to implement, since it is generally difficult to obtain the history of intoxication by the patient himself. The clinician must essentially focus on the symptoms in order to identify the toxic compound ingested and thus establish the appropriate treatment. The latter will essentially depend on the nature of the toxic molecule (s), the subject, the time of ingestion, the severity of the poisoning and the clinical signs.
Dans le cas des intoxications orales, les traitements mis en œuvre à l'heure actuelle pour éviter le passage des toxiques dans le sang recourent soit au lavage gastrique (qui est proscrit dans le cas de produits corrosifs et qui présente des risques au plan respiratoire), soit au charbon actif (dont l'efficacité n'a pas été indiscutablement démontrée et qui, pour cette raison est utilisé faute de mieux et de manière variable selon les hôpitaux).In the case of oral intoxication, the treatments implemented at present to avoid the passage of toxins in the blood resort to either gastric lavage (which is prohibited in the case of corrosive products and which presents respiratory risks) , or with activated charcoal (whose effectiveness has not been incontestably demonstrated and which, for this reason is used for lack of better and in a variable way according to the hospitals).
Dans le cas des intoxications cutanées, il n'existe à l'heure actuelle aucun médicament universel bien toléré et ayant une action rapide.In the case of skin intoxication, there is currently no universal drug that is well tolerated and has rapid action.
Le phénomène d'extraction de composés toxiques par; des emulsions simples et multiples est déjà connu depuis plusieurs années. L'utilisation des emulsions simples huile/eau pour la purification des effluents industriels par extraction a déjà été mise en œuvre sur de nombreux polluants métalliques ou organiques, en utilisant un couple extractant/désextractant adapté. Mais l'utilisation thérapeutique de ces emulsions simples n'a jamais été envisagée. En outre, ces systèmes présentent une durée de vie volontairement très limitée (nécessaire pour une récupération et un recyclage rapides des constituants) qui les rendent complètement inadaptés à une telle application. Par ailleurs, l'administration orale des emulsions simples eau/huile et des emulsions multiples eau/huile/eau pour le traitement d'overdoses de médicaments a été envisagée il y a une vingtaine d'années, uniquement au niveau de la recherche. Mais ces systèmes -émulsionnés ne renferment pas d'extractant, réduisant ainsi de façon sensible la vitesse de capture. En outre, les emulsions multiples eau/huile/eau qui ont déjà été envisagées présentent une stabilité précaire.The phenomenon of extraction of toxic compounds by; single and multiple emulsions has already been known for several years. The use of simple oil / water emulsions for the purification of industrial effluents by extraction has already been implemented on many metallic or organic pollutants, using a suitable extractant / deextractant couple. However, the therapeutic use of these simple emulsions has never been envisaged. In addition, these systems have a deliberately very limited lifetime (necessary for rapid recovery and recycling of the constituents) which make them completely unsuitable for such an application. In addition, oral administration of single water / oil emulsions and multiple water / oil / water emulsions for the treatment of drug overdoses was considered some twenty years ago, solely at the research level. But these systems -emulsified do not contain extractant, thereby significantly reducing the speed of capture. In addition, the multiple water / oil / water emulsions which have already been envisaged have precarious stability.
Devant ce constat de relative inefficacité des traitements mis en œuvre actuellement et compte tenu des implications évidentes dans le domaine de la santé publique, l'invention permet de fournir une alternative originale et efficace dans les traitements de première nécessité destinés aux urgences industrielles, militaires, hospitalières, domestiques et environnementales.Faced with this observation of the relative ineffectiveness of the treatments currently implemented and taking into account the obvious implications in the field of public health, the invention makes it possible to provide an original and effective alternative in the essential treatments intended for industrial, military emergencies, hospital, domestic and environmental.
Ainsi, l'invention a pour but de permettre le traitement des intoxications orales qui ont pour origine l'ingestion de produits pharmaceutiques et non pharmaceutiques, mais aussi les intoxications cutanées d'origine domestique, industrielle ou militaire.Thus, the invention aims to allow the treatment of oral poisoning which originates from the ingestion of pharmaceutical and non-pharmaceutical products, but also skin intoxication of domestic, industrial or military origin.
La présente invention a pour but l'utilisation d'émulsions très stables en raison de la présence dans ces emulsions de tensioactifs polymères.The present invention aims to use very stable emulsions due to the presence in these emulsions of polymeric surfactants.
La présente invention concerne l'utilisation d'émulsions simples ou multiples comprenant dans leur phase organique un ou plusieurs composés extractants capables, lorsque lesdites emulsions sont mises en contact avec un milieu, encore désigné milieu externe, soit biologique tel que le liquide gastrique, la peau ou le sang, soit artificiel tel que des surfaces métalliques ou plastiques, d'extraire dudit milieu des molécules toxiques déterminées susceptibles de se lier audit ou auxdits extractants, pour la préparation de compositions pharmaceutiques destinées à la prévention ou au traitement d'intoxications par voie orale, topique ou parentérale, ou pour la détoxication de surfaces par simple application sur les surfaces susmentionnées.The present invention relates to the use of single or multiple emulsions comprising in their organic phase one or more extracting compounds capable, when said emulsions are brought into contact with a medium, also designated external medium, either biological such as gastric liquid, skin or blood, either artificial or metallic or plastic surfaces, to extract from said medium specific toxic molecules capable of binding to said or said extractants, for the preparation of pharmaceutical compositions intended for the prevention or treatment of intoxication by oral, topical or parenteral, or for detoxifying surfaces by simple application to the aforementioned surfaces.
La présente invention concerne l'utilisation telle que mentionnée ci-dessus, d'émulsions simples eau dans huile, ou multiples eau dans hujle dans eau, dont la phase aqueuse interne comprend un ou plusieurs composés désextractants, piégeant les molécules toxiques extraites du milieu externe.The present invention relates to the use as mentioned above, of simple water in oil emulsions, or multiple water in hujle in water emulsions, the internal aqueous phase of which comprises one or more de-extracting compounds, trapping the toxic molecules extracted from the external medium .
Par "composé désextractant", on désigne une molécule qui va réagir chimiquement avec le complexe formé par la molécule toxique et l'extractant, ce qui d'une part permet de régénérer l'extractant, et d'autre part, de piéger la molécule toxique.By "deextracting compound" is meant a molecule which will react chemically with the complex formed by the toxic molecule and the extractant, which on the one hand makes it possible to regenerate the extractant, and on the other hand, to trap the molecule toxic.
La présente invention concerne également l'utilisation susmentionnée, caractérisée en ce que l'extractant est choisi parmi :The present invention also relates to the abovementioned use, characterized in that the extractant is chosen from:
- les dérivés aminés, tels que les aminés primaires, secondaires ou tertiaires ou les sels d'ammonium quaternaire, comportant une ou plusieurs chaînes carbonées -comprenant chacune d'environ 1 à 18 atomes de carbone, notamment la trioctylamine ou la trilaurylamine, lorsque la molécule toxique à éliminer présente un caractère acide ou anionique,- amino derivatives, such as primary, secondary or tertiary amines or quaternary ammonium salts, comprising one or more carbon chains each comprising around 1 to 18 carbon atoms, in particular trioctylamine or trilaurylamine, when the toxic molecule to be eliminated has an acid or anionic character,
- les acides organiques, tels que les acides organophosphorés, les acides thiophosphorés, les acides carboxyliques, comportant une ou plusieurs chaînes carbonées comprenant chacune d'environ 1 à 18 atomes de carbone, lorsque la molécule toxique à éliminer présente un caractère basique ou cationique,organic acids, such as organophosphorus acids, thiophosphorus acids, carboxylic acids, comprising one or more carbon chains each comprising from approximately 1 to 18 carbon atoms, when the toxic molecule to be eliminated has a basic or cationic character,
- les molécules solvatantes, telles que les alcools, les organophosphates, les oxydes de phosphine, les organosulfures ou les sulfoxydes, comportant une ou plusieurs chaînes carbonées comprenant chacune d'environ 1 à 18 atomes de carbone, lorsque la molécule toxique à éliminer présente un caractère neutre.- the solvating molecules, such as alcohols, organophosphates, phosphine oxides, organosulfides or sulfoxides, comprising one or more carbon chains each comprising about 1 to 18 carbon atoms, when the toxic molecule to be eliminated has a neutral character.
L'expression "molécule présentant un caractère acide " désigne au sens large un - acide de Lewis (accepteur d'électrons) tel qu'un acide faible, notamment l'acide acétique, l'acide lactique, l'acide citrique, l'acide acétylsalicylique ou l'acide cyanhydrique.The expression “molecule having an acid character” designates in the broad sense a - Lewis acid (electron acceptor) such as a weak acid, in particular acetic acid, lactic acid, citric acid, acetylsalicylic acid or hydrocyanic acid.
L'expression "molécule présentant un caractère anionique" désigne un anion aqueux tel que par exemple les ions cyanure, fluorure ou chlorure, ou des complexes anioniques métalliques tels que par exemple FeC-U" ou AuCLf-The expression "molecule having an anionic character" designates an aqueous anion such as for example cyanide, fluoride or chloride ions, or anionic metal complexes such as for example FeC-U " or AuCLf-
L'expression "molécule présentant un caractère basique" désigne au sens large une base de Lewis (donneur d'électrons) possédant par exemple un atome d'azote (protonable) telle que Toxine, l'urée, l'ammoniaque, la quinine ou les amphétamines, ou possédant un atome de soufre (protonable) comme par exemple l'ion sulfure ou l'ion sulfite.The expression “molecule having a basic character” designates in the broad sense a Lewis base (electron donor) having for example a nitrogen atom (protonable) such as Toxin, urea, ammonia, quinine or amphetamines, or having a sulfur atom (protonable) such as for example the sulfide ion or the sulfite ion.
L'expression "molécule présentant un caractère cationique" désigne un cation aqueux tel que par exemple l'ion ammonium ou les cations métalliques.The expression “molecule having a cationic character” designates an aqueous cation such as for example the ammonium ion or the metal cations.
L'expression "molécule présentant un caractère neutre" désigne une molécule ne présentant pas de propriétés échangeuses d'électrons marquées, telle que par exemple les alcools (éthanol), les cétones, les éthers, le paracétamol...The expression “molecule having a neutral character” designates a molecule having no marked electron exchange properties, such as for example alcohols (ethanol), ketones, ethers, paracetamol, etc.
Un acide organophosphoré préféré, parmi les extractants, est l'acide di-2- éthylhexylphosphorique.A preferred organophosphorus acid, among the extractants, is di-2-ethylhexylphosphoric acid.
Parmi les alcools, on utilise de préférence, à titre d' extractants, l'octanol ou le décanol.Among the alcohols, octanol or decanol are preferably used as extractants.
La présente invention concerne l'utilisation telle que définie ci-dessus, caractérisée en ce que le désextractant est choisi parmi : - les bases telles que NaOH, KOH, Na2CO3, lorsque la molécule toxique à éliminer présente un caractère acide ou anionique,The present invention relates to the use as defined above, characterized in that the deextractant is chosen from: - bases such as NaOH, KOH, Na 2 CO 3 , when the toxic molecule to be eliminated has an acid or anionic character,
- les sels ioniques tels que NaCl, -NEUCl ou NaNO3, lorsque la molécule toxique à éliminer présente un caractère anionique,- ionic salts such as NaCl, -NEUCl or NaNO 3 , when the toxic molecule to be eliminated has an anionic character,
- les acides tels que l'acide chlorhydrique ou l'acide lactique, lorsque la molécule toxique à éliminer présente un caractère basique ou cationique,- acids such as hydrochloric acid or lactic acid, when the toxic molecule to be eliminated has a basic or cationic character,
- les composés à caractère oxydo-réducteur ou complexant, tels que les sels de chrome(VI), la thiourée, l'acide éthylène diamine tétracétique, des dérivés chlorés ou fluorés, l'acide ascorbique, lorsque la molécule toxique à éliminer présente un caractère neutre.- compounds with an oxidoreductive or complexing character, such as chromium (VI) salts, thiourea, ethylene diamine tetracetic acid, chlorinated or fluorinated derivatives, ascorbic acid, when the toxic molecule to be eliminated has a neutral character.
L'expression "composés à caractère oxydo-réducteur ou complexant" désigne des composés capables de réduire ou d'oxyder le toxique ou de former avec lui un complexe lipophobe.The expression "compounds with an oxidoreducing or complexing character" designates compounds capable of reducing or oxidizing the toxic agent or of forming with it a lipophobic complex.
Selon un mode de réalisation avantageux de la présente invention, l'invention concerne l'utilisation d'émulsions simples eau dans huile comprenant :According to an advantageous embodiment of the present invention, the invention relates to the use of simple water-in-oil emulsions comprising:
- une phase organique externe contenant :- an external organic phase containing:
• un ou plusieurs extractants, tels que définis ci-dessus, la fraction massique du ou des extractants par rapport à la phase organique étant comprise entre environ 0,1 et environ 20%,One or more extractants, as defined above, the mass fraction of the extractant (s) relative to the organic phase being between approximately 0.1 and approximately 20%,
• un ou plusieurs tensioactifs lipophiles à liaison éther, comme les al-kyldiméthicone copolyols, ou à liaison aminé tels que des polyamines condensées à longues chaînes, ou des esters de sorbitanne ou de glycol, la fraction massique du ou des tensioactifs lipophiles par rapport à la phase organique étant comprise entre environ 0,5 et environ 20%,One or more ether-bonded lipophilic surfactants, such as al-kyldimethicone copolyols, or amine-bonded surfactants such as long chain condensed polyamines, or sorbitan or glycol esters, the mass fraction of the lipophilic surfactant (s) relative to the organic phase being between approximately 0.5 and approximately 20%,
• des hydrocarbures (qsp) tels que des paraffines liquides, du perhydrosqualène ou des silicones ou des esters synthétiques,• hydrocarbons (qs) such as liquid paraffins, perhydrosqualene or silicones or synthetic esters,
- une phase aqueuse interne contenant un ou plusieurs désextractants tels que définis ci-dessus, et éventuellement un additif tel qu'un électrolyte ou un sucre, le rapport massique de la phase aqueuse interne par rapport à l'émulsion étant compris entre environ 1 et environ 80%, de préférence entre environ 20% et environ 70%.an internal aqueous phase containing one or more deextractants as defined above, and optionally an additive such as an electrolyte or a sugar, the mass ratio of the internal aqueous phase relative to the emulsion being between approximately 1 and about 80%, preferably between about 20% and about 70%.
Selon un mode de réalisation avantageux de la présente* invention, l'invention concerne l'utilisation d'émulsions multiples eau dans huile dans eau comprenant : - une phase aqueuse externe contenant un ou plusieurs tensioactifs hydrophiles à liaison éther tels que des copolymères d'oxyde d'éthylène et d'oxyde de propylène, des alcools gras oxyéthylénés, ou des tensioactifs hydrophiles à liaison ester tels que des esters de sorbitanne polyoxyéthylénés, la fraction massique de ces tensioactifs par rapport à la phase aqueuse externe étant comprise entre environ 0,1 et environ 10%.According to an advantageous embodiment of the present invention, the invention relates to the use of multiple water-in-oil-in-water emulsions comprising: an external aqueous phase containing one or more hydrophilic surfactants with ether bond such as copolymers of ethylene oxide and propylene oxide, oxyethylenated fatty alcohols, or hydrophilic surfactants with ester bond such as polyoxyethylenated sorbitan esters , the mass fraction of these surfactants relative to the external aqueous phase being between approximately 0.1 and approximately 10%.
- une émulsion simple interne telle que définie ci-dessus, comprenant :- a simple internal emulsion as defined above, comprising:
* une phase organique séparant la phase aqueuse externe ci-dessus et la phase aqueuse interne ci-dessous, cette phase organique contenant :* an organic phase separating the above external aqueous phase and the below internal aqueous phase, this organic phase containing:
• un ou plusieurs extractants, tels que définis ci-dessus, la fraction massique du ou des extractants par rapport à la phase organique étant comprise entre environ 0,1 et environ 20%,One or more extractants, as defined above, the mass fraction of the extractant (s) relative to the organic phase being between approximately 0.1 and approximately 20%,
• un ou plusieurs tensioactifs lipophiles à liaison éther, comme les alkyldiméthicone copolyols, ou à liaison aminé tels que des polyamines condensées à longues chaînes, ou des esters de sorbitanne ou de glycol, la fraction massique du ou des tensioactifs lipophiles par rapport à la phase organique étant comprise entre environ 0,5 et environ 20%,• one or more lipophilic surfactants with ether bond, such as alkyldimethicone copolyols, or with amino bond such as condensed polyamines with long chains, or sorbitan or glycol esters, the mass fraction of the lipophilic surfactant (s) relative to the phase organic being between approximately 0.5 and approximately 20%,
• des hydrocarbures tels que des paraffines liquides, du perhydrosqualène ou des silicones ou des esters synthétiques,• hydrocarbons such as liquid paraffins, perhydrosqualene or silicones or synthetic esters,
* une phase aqueuse interne contenant un ou plusieurs désextractants tels que définis ci-dessus, la phase aqueuse externe représentant environ 1 à environ 80% en masse de l'émulsion simple, et de préférence d'environ 20% à environ 70%.* an internal aqueous phase containing one or more de-extractants as defined above, the external aqueous phase representing approximately 1 to approximately 80% by mass of the simple emulsion, and preferably from approximately 20% to approximately 70%.
Selon un mode de réalisation avantageux, l'invention concerne l'utilisation telle que mentionnée ci-dessus, d'émulsions simples ou multiples, pour la détoxication de molécules acides, telle que l'acide acétylsalicylique, caractérisée en ce que l'extractant est une aminé tertiaire, notamment la trioctylamine ou la trilaurylamine, et en ce que le désextractant est la soude NaOH.According to an advantageous embodiment, the invention relates to the use as mentioned above, of single or multiple emulsions, for the detoxification of acid molecules, such as acetylsalicylic acid, characterized in that the extractant is a tertiary amine, in particular trioctylamine or trilaurylamine, and in that the deextractant is sodium hydroxide NaOH.
Selon un mode de réalisation avantageux, l'invention concerne l'utilisation telle que mentionnée ci-dessus, d'émulsions simples eau dans huile, pour la détoxication de molécules acides, telle que l'acide acétylsalicylique, comprenant :According to an advantageous embodiment, the invention relates to the use as mentioned above, of simple water-in-oil emulsions, for the detoxification of acid molecules, such as acetylsalicylic acid, comprising:
- une phase organique externe contenant :- an external organic phase containing:
• de la paraffine liquide, • de la trilaurylamine à titre d'extractant, à raison d'environ 0,1% à environ 3% en masse par rapport à la phase organique externe,• liquid paraffin, • trilaurylamine as an extractant, at a rate of approximately 0.1% to approximately 3% by mass relative to the external organic phase,
• du cétyldiméthicone copolyol à titre d'agent tensioactif lipophile, à raison d'environ 1 à environ 10% en masse par rapport à la phase organique externe,Cetyldimethicone copolyol as lipophilic surfactant, at a rate of approximately 1 to approximately 10% by mass relative to the external organic phase,
- une phase aqueuse interne contenant, à titre de désextractant, de la soude, à une concentration telle que le pH soit supérieur ou égal à 13, le rapport massique entre la phase aqueuse et l'émulsion totale étant compris entre environ 10% et environ 70%, et de préférence égal à environ 50%.an internal aqueous phase containing, as deextractant, sodium hydroxide, at a concentration such that the pH is greater than or equal to 13, the mass ratio between the aqueous phase and the total emulsion being between approximately 10% and approximately 70%, and preferably equal to about 50%.
Selon un mode de réalisation avantageux, l'invention concerne l'utilisation telle que mentionnée ci-dessus, d'émulsions multiples eau dans huile dans eau, pour la détoxication de molécules acides, telle que l'acide acétylsalicylique, comprenant :According to an advantageous embodiment, the invention relates to the use as mentioned above, of multiple water-in-oil-in-water emulsions, for the detoxification of acid molecules, such as acetylsalicylic acid, comprising:
- une phase aqueuse externe contenant un copolymère d'oxyde d'éthylène et d'oxyde de propylène à titre d'agent tensioactif hydrophile, à raison d'environ 0,5 à environ 2% en masse par rapport à la masse totale de la phase aqueuse externe,an external aqueous phase containing a copolymer of ethylene oxide and propylene oxide as hydrophilic surfactant, at a rate of approximately 0.5 to approximately 2% by mass relative to the total mass of the external aqueous phase,
- une phase organique séparant la phase aqueuse externe ci-dessus et la phase aqueuse interne ci-dessous, et contenant :an organic phase separating the above external aqueous phase and the below internal aqueous phase, and containing:
• de la paraffine liquide,• liquid paraffin,
• de la trilaurylamine à titre d'extractant, à raison d'environ 0,1% à environ 3% en masse par rapport à la masse totale de la phase organique,• trilaurylamine as an extractant, at a rate of approximately 0.1% to approximately 3% by mass relative to the total mass of the organic phase,
• du cétyldiméthicone copolyol à titre d'agent tensioactif lipophile, à raison d'environ 1 à environ 10% en masse par rapport à la masse totale de la phase organique,Cetyldimethicone copolyol as lipophilic surfactant, at a rate of approximately 1 to approximately 10% by mass relative to the total mass of the organic phase,
- une phase aqueuse interne contenant, à titre de désextractant, de la soude, à une concentration telle que le pH soit supérieur ou égal à 13, et du sulfate de magnésium, à raison d'environ 2 à environ 6%' en masse par rapport à la masse totale de la phase aqueuse interne, le rapport massique entre la phase aqueuse interne et la phase organique étant compris entre environ 25% et environ 200%, et de préférence égal à environ 100%, et le rapport massique entre la phase aqueuse externe et l'émulsion simple primaire étant compris entre environ 10% et environ 90%, et de préférence égal à environ 25%.- an internal aqueous phase containing, as désextractant, soda, at a concentration such that the pH is greater than or equal to 13, and magnesium sulfate, from about 2 to about 6% 'by weight relative to the total mass of the internal aqueous phase, the mass ratio between the internal aqueous phase and the organic phase being between approximately 25% and approximately 200%, and preferably equal to approximately 100%, and the mass ratio between the phase external aqueous and the primary single emulsion being between approximately 10% and approximately 90%, and preferably equal to approximately 25%.
Selon un mode de réalisation avantageux, l'invention concerne l'utilisation telle que mentionnée ci-dessus, d'émulsions simples ou multiples, pour la détoxication de -composés à caractère acido-basique très peu marqué, tels que le paracétamol, caractérisée en ce que l'extractant utilisé est un alcool à longue chaîne, notamment l'octanol, et en ce que le désextractant est NaOH.According to an advantageous embodiment, the invention relates to the use as mentioned above, of single or multiple emulsions, for the detoxification of -composites of very weak acid-base character, such as paracetamol, characterized in that the extractant used is a long-chain alcohol, in particular octanol, and in that the deextractant is NaOH.
Selon un mode de réalisation avantageux, l'invention concerne l'utilisation telle que mentionnée ci-dessus, d'émulsions simples eau dans huile comprenant :According to an advantageous embodiment, the invention relates to the use as mentioned above, of simple water in oil emulsions comprising:
- une phase organique externe contenant :- an external organic phase containing:
• de la paraffine liquide,• liquid paraffin,
• de l'octanol à titre d'extractant, à raison d'environ 0,1% à environ 20% en masse par rapport à la phase organique externe,• octanol as an extractant, at a rate of approximately 0.1% to approximately 20% by mass relative to the external organic phase,
• une polyamine condensée sur de l'acide succinique substituée par une chaîne polyisobutène, telle que l'ECA 4360, à titre d'agent tensioactif lipophile, à raison d'environ 1 à environ 10% en masse par rapport à la phase organique externe,• a polyamine condensed on succinic acid substituted with a polyisobutene chain, such as ECA 4360, as lipophilic surfactant, in a proportion of approximately 1 to approximately 10% by mass relative to the external organic phase ,
- une phase aqueuse interne contenant, à titre de désextractant, de la soude à une concentration telle que le pH soit supérieur à 13, le rapport massique entre la phase aqueuse et l'émulsion totale étant compris entre environ 10% et environ 70%, et de préférence égal à environ 50%.an internal aqueous phase containing, as a de-extractant, sodium hydroxide at a concentration such that the pH is greater than 13, the mass ratio between the aqueous phase and the total emulsion being between approximately 10% and approximately 70%, and preferably equal to about 50%.
Selon un mode de réalisation avantageux, l'invention concerne l'utilisation telle que mentionnée ci-dessus, d'émulsions simples ou multiples, pour la détoxication de composés tels que la zopicloneND, caractérisée en ce que l'extractant utilisé est un acide organothiophosphoré à longue chaîne, notamment l'acide di-éthylhexyl- monothiophosphinique (Cyanex 302), et en ce que le désextractant est l'acide chlorhydrique.According to an advantageous embodiment, the invention relates to the use as mentioned above, of single or multiple emulsions, for the detoxification of compounds such as zopiclone ND , characterized in that the extractant used is an acid long-chain organothiophosphorus, in particular di-ethylhexyl-monothiophosphinic acid (Cyanex 302), and in that the deextractant is hydrochloric acid.
Selon un mode de réalisation avantageux, l'invention concerne l'utilisation telle que mentionnée ci-dessus, d'émulsions simples eau dans huile comprenant :According to an advantageous embodiment, the invention relates to the use as mentioned above, of simple water in oil emulsions comprising:
- une phase organique externe contenant :- an external organic phase containing:
• de la paraffine liquide,• liquid paraffin,
• du Cyanex 302 à titre d'extractant, à raison d'environ 0,1% à environ 5% en masse par rapport à la phase organique externe,• Cyanex 302 as an extractant, at a rate of approximately 0.1% to approximately 5% by mass relative to the external organic phase,
• de l'ECA 4360 à titre d'agent tensioactif lipophile, à raison d'environ 1 à environ 10% en masse par rapport à la phase organique,ECA 4360 as lipophilic surfactant, at a rate of approximately 1 to approximately 10% by mass relative to the organic phase,
- une phase aqueuse interne contenant de l'acide chlorhydrique à une concentration supérieure à 0,2 mol.L"1, à titre de désextractant, le rapport massique entre la phase aqueuse et l'émulsion totale étant compris entre environ 10% et environ 70%, et de préférence égal à environ 50%.an internal aqueous phase containing hydrochloric acid at a concentration greater than 0.2 mol.L "1 , as a de-extractant, the mass ratio between the aqueous phase and the total emulsion being between approximately 10% and approximately 70%, and preferably equal to approximately 50%.
La présente invention concerne plus particulièrement l'utilisation d'émulsions simples ou multiples telle que définies ci-dessus, pour la préparation de compositions destinées à la décontamination de surfaces.The present invention relates more particularly to the use of single or multiple emulsions as defined above, for the preparation of compositions intended for the decontamination of surfaces.
La présente invention a plus particulièrement pour objet l'utilisation d'émulsions simples ou multiples telle que définies ci-dessus, pour la préparation de compositions pharmaceutiques destinées à la prévention ou au traitement d'intoxications par voie orale, topique ou parentérale.The present invention more particularly relates to the use of single or multiple emulsions as defined above, for the preparation of pharmaceutical compositions intended for the prevention or treatment of intoxication by oral, topical or parenteral route.
La présente invention a également pour objet l'utilisation d'émulsions simples ou multiples telles que définies ci-dessus, pour la préparation de dispositifs médicaux destinés à la prévention ou au traitement d'intoxications par voie orale, topique ou parentérale.The present invention also relates to the use of single or multiple emulsions as defined above, for the preparation of medical devices intended for the prevention or treatment of intoxication by oral, topical or parenteral route.
La présente invention concerne également une composition pharmaceutique caractérisée en ce qu'elle comprend une emulsion simple ou multiple telle que définie ci-dessus, le cas échéant en association avec un véhicule pharmaceutiquement acceptable.The present invention also relates to a pharmaceutical composition characterized in that it comprises a single or multiple emulsion as defined above, where appropriate in combination with a pharmaceutically acceptable vehicle.
Une composition pharmaceutique avantageuse selon l'invention est caractérisée en ce qu'elle se présente sous une forme pouvant être administrée par voie orale, unique ou réitérée, notamment à raison d'environ 10 à environ 500 g.An advantageous pharmaceutical composition according to the invention is characterized in that it is in a form which can be administered by the oral route, single or repeated, in particular at a rate of approximately 10 to approximately 500 g.
Une composition pharmaceutique avantageuse selon l'invention est caractérisée en ce qu'elle se présente sous une forme pouvant être administrée par voie topique, notamment à raison d'environ 2 à environ 50 mg/cm2 de peau.An advantageous pharmaceutical composition according to the invention is characterized in that it is in a form which can be administered topically, in particular at a rate of approximately 2 to approximately 50 mg / cm 2 of skin.
Une composition pharmaceutique avantageuse selon l'invention est caractérisée en ce qu'elle se présente sous une forme pouvant être utilisée pour la voie parentérale par une circulation extracorporelle, notamment à raison d'environ 500 à environ 1000 g.An advantageous pharmaceutical composition according to the invention is characterized in that it is in a form which can be used for the parenteral route by an extracorporeal circulation, in particular at a rate of approximately 500 to approximately 1000 g.
La présente invention concerne également toute emulsion multiple eau dans huile dans eau comprenant dans sa phase organique un ou plusieurs composés extractants tels que définis ci-dessus.The present invention also relates to any multiple water-in-oil-in-water emulsion comprising in its organic phase one or more extracting compounds as defined above.
Selon un mode de réalisation avantageux de la présente invention, l'invention concerne toute emulsion multiple telle que définie ci-dessus, comprenant dans sa phase organique un ou plusieurs tensioactifs lipophiles tels que définis ci-dessus. Une emulsion multiple avantageuse de la présente invention comprend dans sa phase aqueuse interne un ou plusieurs composés désextractants tels que définis ci- dessus, et d'éventuels additifs tels que des électrolytes ou des sucres.According to an advantageous embodiment of the present invention, the invention relates to any multiple emulsion as defined above, comprising in its organic phase one or more lipophilic surfactants as defined above. An advantageous multiple emulsion of the present invention comprises in its internal aqueous phase one or more deextracting compounds as defined above, and optional additives such as electrolytes or sugars.
Les électrolytes préférés sont le chlorure de sodium ou le sulfate de magnésium.The preferred electrolytes are sodium chloride or magnesium sulfate.
Les sucres préférés sont le glucose ou le saccharose.The preferred sugars are glucose or sucrose.
Une emulsion multiple avantageuse de la présente invention comprend dans sa phase aqueuse externe un ou plusieurs tensioactifs hydrophiles tels que définis ci- dessus.An advantageous multiple emulsion of the present invention comprises in its external aqueous phase one or more hydrophilic surfactants as defined above.
Une emulsion multiple particulièrement avantageuse de la présente invention est une emulsion multiple qui comprend :A particularly advantageous multiple emulsion of the present invention is a multiple emulsion which comprises:
- une phase aqueuse externe contenant un ou plusieurs tensioactifs hydrophiles à liaison éther tels que des copolymères d'oxyde d'éthylène et d'oxyde de propylène, des alcools gras oxyéthylénés, ou des tensioactifs hydrophiles à liaison ester tels que des esters de sorbitanne polyoxyéthylénés, la fraction massique de ces tensioactifs par rapport à la phase aqueuse externe étant comprise entre environ 0,1 et environ 10%.an external aqueous phase containing one or more hydrophilic ether-surfactants such as copolymers of ethylene oxide and propylene oxide, oxyethylenated fatty alcohols, or hydrophilic surfactants with ester bond such as polyoxyethylenated sorbitan esters , the mass fraction of these surfactants relative to the external aqueous phase being between approximately 0.1 and approximately 10%.
— une emulsion simple interne telle que définie ci-dessus, comprenant :- a simple internal emulsion as defined above, comprising:
* une phase organique séparant la phase aqueuse externe ci-dessus et la phase aqueuse interne ci-dessous, cette phase organique contenant :* an organic phase separating the above external aqueous phase and the below internal aqueous phase, this organic phase containing:
• un ou plusieurs extractants, tels que définis ci-dessus, la fraction massique du ou des extractants par rapport à la phase organique étant comprise entre environ 0,1 et environ 20%,One or more extractants, as defined above, the mass fraction of the extractant (s) relative to the organic phase being between approximately 0.1 and approximately 20%,
• un ou plusieurs tensioactifs lipophiles à liaison éther, comme les alkyldiméthicone copolyols, ou à liaison aminé tels que des polyamines condensées à longues chaînes, ou des esters de sorbitanne ou de glycol, la fraction massique du ou des tensioactifs lipophiles par rapport à la phase organique étant comprise entre environ 0,5 et environ 20%,• one or more lipophilic surfactants with ether bond, such as alkyldimethicone copolyols, or with amino bond such as condensed polyamines with long chains, or sorbitan or glycol esters, the mass fraction of the lipophilic surfactant (s) relative to the phase organic being between approximately 0.5 and approximately 20%,
• des hydrocarbures tels que des paraffines liquides, du perhydrosqualène ou des silicones ou des esters synthétiques,• hydrocarbons such as liquid paraffins, perhydrosqualene or silicones or synthetic esters,
* une phase aqueuse interne contenant un ou plusieurs désextractants tels que définis ci-dessus, la phase aqueuse externe représentant environ 1 à environ 80% en masse de l'émulsion simple, et de préférence d'environ 10% à environ 70%. La présente invention concerne également une emulsion multiple telle que définie ci-dessus, pour la détoxication de molécules acides, telle que l'acide acétylsalicylique, comprenant :* an internal aqueous phase containing one or more de-extractants as defined above, the external aqueous phase representing approximately 1 to approximately 80% by mass of the simple emulsion, and preferably from approximately 10% to approximately 70%. The present invention also relates to a multiple emulsion as defined above, for the detoxification of acid molecules, such as acetylsalicylic acid, comprising:
- une phase aqueuse externe contenant un copolymère d'oxyde d'éthylène et d'oxyde de propylène à titre d'agent tensioactif hydrophile, à raison d'environ 0,5 à environ 2% en masse par rapport à la masse totale de la phase aqueuse externe,an external aqueous phase containing a copolymer of ethylene oxide and propylene oxide as hydrophilic surfactant, at a rate of approximately 0.5 to approximately 2% by mass relative to the total mass of the external aqueous phase,
- une phase organique séparant la phase aqueuse externe ci-dessus et la phase aqueuse interne ci-dessous, et contenant :an organic phase separating the above external aqueous phase and the below internal aqueous phase, and containing:
• de la paraffine liquide,• liquid paraffin,
• de la trilaurylamine à titre d'extractant, à raison d'environ 0,1% à environ 3% en masse par rapport à la masse totale de la phase organique,• trilaurylamine as an extractant, at a rate of approximately 0.1% to approximately 3% by mass relative to the total mass of the organic phase,
• du cétyldiméthicone copolyol à titre d'agent tensioactif lipophile, à raison d'environ 1 à environ 10% en masse par rapport à la masse totale de la phase organique,Cetyldimethicone copolyol as lipophilic surfactant, at a rate of approximately 1 to approximately 10% by mass relative to the total mass of the organic phase,
- une phase aqueuse interne contenant à titre de désextractant de la soude, à une concentration telle que le pH soit supérieur ou égal à 13, et du sulfate de magnésium, à raison d'environ 2 à environ 6% en masse par rapport à la masse totale de la phase aqueuse interne, le rapport massique entre la phase aqueuse interne et la phase organique étant compris entre environ 25% et environ 200%, et de préférence égal à environ 100%, et le rapport massique entre la phase aqueuse externe et l'émulsion simple primaire étant compris entre environ 10% et environ 90%, et de préférence égale à environ 25%. an internal aqueous phase containing, as a de-extractant, sodium hydroxide, at a concentration such that the pH is greater than or equal to 13, and magnesium sulphate, at a rate of approximately 2 to approximately 6% by mass relative to total mass of the internal aqueous phase, the mass ratio between the internal aqueous phase and the organic phase being between approximately 25% and approximately 200%, and preferably equal to approximately 100%, and the mass ratio between the external aqueous phase and the primary single emulsion being between approximately 10% and approximately 90%, and preferably equal to approximately 25%.
PARTIE EXPÉRIMENTALEEXPERIMENTAL PART
Le principe de l'extraction de molécules toxiques par un système émulsionné (emulsion eau dans huile ou emulsion eau dans huile dans eau) consiste :The principle of the extraction of toxic molecules by an emulsified system (water in oil emulsion or water in oil in water emulsion) consists of:
1) à introduire dans la phase organique une molécule lipophile qui va jouer le rôle d'un extractant en réagissant chimiquement avec la molécule toxique à l'interface avec la phase aqueuse externe, et en formant avec celle-ci un composé liposoluble qui traverse la membrane organique, sous l'effet de son gradient de concentration.1) to introduce into the organic phase a lipophilic molecule which will play the role of an extractant by reacting chemically with the toxic molecule at the interface with the external aqueous phase, and by forming with the latter a liposoluble compound which crosses the organic membrane, under the effect of its concentration gradient.
2) à incorporer dans la phase aqueuse interne une molécule qui va réagir chimiquement à l'interface interne avec le complexe lipophile précédemment formé, ce qui, d'une part, permet de régénérer l'extractant et, d'autre part, de piéger la molécule toxique en phase interne.2) to incorporate into the internal aqueous phase a molecule which will react chemically at the internal interface with the lipophilic complex previously formed, which, on the one hand, makes it possible to regenerate the extractant and, on the other hand, to trap the toxic molecule internally.
Définition et préparation des systèmesDefinition and preparation of systems
Deux systèmes sont envisagés : une emulsion simple eau dans huile (système I) et une emulsion multiple eau dans huile dans eau (système II).Two systems are envisaged: a simple water in oil emulsion (system I) and a multiple water in oil in water emulsion (system II).
La préparation du système I s'effectue en deux phases :System I preparation takes place in two phases:
1) au cours de la première phase, on prépare une emulsion simple eau dans huile. Cette emulsion simple est stabilisée par un tensioactif lipophile de faible HLB (Hydrophile/Lipophile Balance) et contient de fines gouttelettes de phase aqueuse interne de diamètre 0,5 à 1 μm. Elle se présente comme un lait relativement visqueux.1) during the first phase, a simple water-in-oil emulsion is prepared. This simple emulsion is stabilized by a lipophilic surfactant of low HLB (Hydrophilic / Lipophilic Balance) and contains fine droplets of internal aqueous phase with a diameter of 0.5 to 1 μm. It is presented as a relatively viscous milk.
2) au cours de la seconde phase, l'émulsion simple obtenue précédemment est dispersée à son tour dans la solution contenant le composé tonique. Cette seconde étape requiert l'intervention d'une agitation modérée, fournie par un agitateur magnétique, dans l'étude in vitro.2) during the second phase, the simple emulsion obtained previously is in turn dispersed in the solution containing the tonic compound. This second step requires the intervention of moderate agitation, provided by a magnetic stirrer, in the in vitro study.
La préparation du système II s'effectue également en deux phases :System II is also prepared in two phases:
1) une première phase identique à celle mise en œuvre pour le système I,1) a first phase identical to that implemented for system I,
2) une seconde phase au cours de laquelle l'émulsion simple (appelée primaire) est dispersée dans une solution aqueuse contenant un tensioactif hydrophile. L'émulsion multiple ainsi obtenue est ensuite dispersée dans la solution contenant le composé toxique. Principe de l'extraction2) a second phase during which the simple emulsion (called primary) is dispersed in an aqueous solution containing a hydrophilic surfactant. The multiple emulsion thus obtained is then dispersed in the solution containing the toxic compound. Principle of extraction
Au cours du contact entre le système émulsionné et la solution, le composé toxique va traverser la solution organique pour être recueilli et piégé dans les gouttelettes de phase aqueuse interne.During the contact between the emulsified system and the solution, the toxic compound will pass through the organic solution to be collected and trapped in the droplets of internal aqueous phase.
L'originalité et l'efficacité du procédé de la présente invention reposent sur deux aspects particulièrement importants : la présence dans la solution organique d'une molécule (transporteur ou extractant) capable d'aider au transport du composé toxique dans cette phase et la présence dans la phase aqueuse interne d'un agent piégeant (désextractant) qui détruit le complexe transporteur-toxique et réagit avec ce dernier pour le transformer en une espèce très lipophobe. Le transporteur ainsi régénéré diffuse pour réagir avec une nouvelle molécule de composé toxique.The originality and the efficiency of the process of the present invention are based on two particularly important aspects: the presence in the organic solution of a molecule (transporter or extractant) capable of helping the transport of the toxic compound in this phase and the presence in the internal aqueous phase of a trapping agent (de-extractant) which destroys the toxic-transporter complex and reacts with the latter to transform it into a very lipophobic species. The transporter thus regenerated diffuses to react with a new molecule of toxic compound.
EXEMPLE DE L'ASPIRINE (ACIDE ACETYLSALICYLIQUE)EXAMPLE OF ASPIRIN (ACETYLSALICYLIC ACID)
I - Rappel théorique :I - Theoretical reminder:
L'acide acétylsalicylique sera noté HA par souci de simplification. Dans ce cas, le transporteur est une aminé tertiaire à longue chaîne (R3N), molécule à caractère basique faible, qui est très peu soluble dans l'eau.Acetylsalicylic acid will be denoted HA for the sake of simplification. In this case, the transporter is a long chain tertiary amine (R 3 N), a molecule with a weak basic character, which is very slightly soluble in water.
A la première interface entre la phase aqueuse externe et la phase organique, la réaction chimique suivante se produit : j At the first interface between the external aqueous phase and the organic phase, the following chemical reaction takes place: j
HAaq + R3Norg R3NHAorg HA aq + R 3 N org R 3 NHA org
La molécule R3.NHA est beaucoup plus lipophile que HA et facilite donc sa solubilisa-ion dans la phase organique.The R 3 .NHA molecule is much more lipophilic than HA and therefore facilitates its solubilization in the organic phase.
L'agent piégeant introduit dans la phase aqueuse interne est la soude. A la deuxième interface entre la phase organique et la phase aqueuse interne, il se produit la réaction chimique suivante :The trapping agent introduced into the internal aqueous phase is sodium hydroxide. At the second interface between the organic phase and the internal aqueous phase, the following chemical reaction takes place:
R3N-HAorg + OH-aq > R3Norg + Naq + H2O L'acide acétylsalicylique est ainsi transformé en ion acétylsalicylate, totalement insoluble dans la phase organique. L'aspirine est ainsi piégée dans la phase interne et R3N, régénéré, repart pour un nouveau cycle.R 3 N-HAo rg + OH- aq > R 3 N org + N aq + H 2 O Acetylsalicylic acid is thus transformed into acetylsalicylate ion, completely insoluble in the organic phase. Aspirin is thus trapped in the internal phase and R 3 N, regenerated, sets out again for a new cycle.
Un tel système chimique est également valable pour d'autres molécules toxiques à caractère acide. L'efficacité de tels systèmes a été démontrée pour des acides organiques tels que l'acide lactique, l'acide ascorbique ou l'acide citrique, et pour des acides minéraux forts ou faibles, tels que l'acide chlorhydrique, l'acide nitrique, l'acide sulfurique, l'acide fluorhydrique ou l'acide cyanhydrique. On peut employer, comme transporteur, des aminés primaires, secondaires et tertiaires, pourvu qu'elles aient une ou plusieurs longues chaînes carbonées (pour minimiser leur solubilité dans l'eau). Cependant, les aminés tertiaires sont les plus efficaces car elles sont les plus basiques.Such a chemical system is also valid for other toxic molecules with an acidic character. The effectiveness of such systems has been demonstrated for organic acids such as lactic acid, ascorbic acid or citric acid, and for strong or weak mineral acids, such as hydrochloric acid, nitric acid. , sulfuric acid, hydrofluoric acid or hydrocyanic acid. Primary, secondary and tertiary amines can be used as the carrier, provided they have one or more long carbon chains (to minimize their solubility in water). However, tertiary amines are the most effective because they are the most basic.
La solution aqueuse interne est une solution basique, constituée d'une base forte comme la soude ou la potasse ou d'une base faible comme le carbonate de sodium ou le carbonate de potassium. Cependant, les bases fortes sont les plus efficaces.The internal aqueous solution is a basic solution, consisting of a strong base like soda or potash or a weak base like sodium carbonate or potassium carbonate. However, strong bases are the most effective.
II - Evaluation des propriétés d'extraction de l'acide acétylsalicylique par les emulsions simples (système I) selon la nature et la concentration des constituants :II - Evaluation of the properties of extraction of acetylsalicylic acid by simple emulsions (system I) according to the nature and the concentration of the constituents:
Différents composants de l'émulsion ont été étudiés :Different components of the emulsion have been studied:
- Solvant organique apolaire : dodécane ou polyisobutène hydrogéné (parleam)- Apolar organic solvent: dodecane or hydrogenated polyisobutene (parleam)
- extractant organique : trioctylamine (C8H1 )3N ou trilaurylamine (C12H25)3N- organic extractant: trioctylamine (C 8 H 1 ) 3 N or trilaurylamine (C 12 H 25 ) 3 N
- tensioactif : ECA 4630 ou Abil EM 90- surfactant: ECA 4630 or Abil EM 90
- phase interne de l'émulsion : soude- internal phase of the emulsion: soda
A) Préparation des emulsions :A) Preparation of emulsions:
Les deux phases sont émulsifiées pendant 3 minutes grâce à un Ulfraturrax tournant à 13 500 tours/min. Le diamètre moyen des gouttes de l'émulsion ainsi obtenue est de l'ordre de 0,5 à 1 μm. B) Extraction in vitro :The two phases are emulsified for 3 minutes using an Ulfraturrax rotating at 13,500 rpm. The average diameter of the drops of the emulsion thus obtained is of the order of 0.5 to 1 μm. B) In vitro extraction:
On met en contact, dans un bêcher, sous agitation mécanique, 50 mL d'émulsion avec 100 mL d'une solution aqueuse contenant 0,02 ou 0,01 mol.L"1 d'aspirine et on suit au cours du temps la concentration résiduelle de l'aspirine dans la phase aqueuse externe. On en déduit alors le pourcentage d'extraction, qui est un paramètre permettant la comparaison de l'efficacité des différentes emulsions préparées.50 ml of emulsion are brought into contact in a beaker, with mechanical stirring, with 100 ml of an aqueous solution containing 0.02 or 0.01 mol.L "1 of aspirin and the time is monitored. residual concentration of aspirin in the external aqueous phase, which gives the percentage of extraction, which is a parameter allowing the comparison of the effectiveness of the various emulsions prepared.
1) Influence de la sonde1) Influence of the probe
Pour déterminer l'influence de la soude, on prépare des emulsions contenant les composants suivants :To determine the influence of soda, emulsions are prepared containing the following components:
Dodécane 46,5 %Dodecane 46.5%
TLA 2,5 %TLA 2.5%
Abil 1 %Abil 1%
NaOH de différentes concentrations : 50 % (par la suite, tous les pourcentages représentent des rapports en masse)NaOH of different concentrations: 50% (thereafter, all percentages represent mass ratios)
Après 3 minutes de contact, on obtient les résultats suivants :After 3 minutes of contact, the following results are obtained:
On observe ainsi l'importance de la présence de soude dans la phase interne. Au- delà de 0,1 mol.L"1, la concentration n'a plus d'effet, dans la mesure où la quantité stœchiométrique OHVaspirine est respectée.We thus observe the importance of the presence of soda in the internal phase. Above 0.1 mol.L "1 , the concentration has no effect, as long as the stoichiometric quantity OHVaspirin is respected.
2) Influence de la concentration de l'extractant2) Influence of the extractant concentration
Afin de déterminer le rôle de la concentration de l'extractant, les 3 formulations suivantes sont comparées ; elles contiennent toutes 2 % d'Abil et 50 % de NaOH 0,1 mol.L"1 et : In order to determine the role of the extractant concentration, the following 3 formulations are compared; they all contain 2% Abil and 50% NaOH 0.1 mol.L "1 and:
On trouve ci-après le pourcentage d'extraction en fonction du temps pour les 3 emulsions :The extraction percentage as a function of time is given below for the 3 emulsions:
On constate donc que les performances sont très nettement supérieures en présence de l'extractant. En effet, l'extraction est totale en moins de 3 minutes en présence de TOA, alors qu'il faut attendre 8 minutes pour avoir plus de 90% d'extraction sans TOA.It can therefore be seen that the performances are very clearly superior in the presence of the extractant. Indeed, the extraction is complete in less than 3 minutes in the presence of TOA, while it is necessary to wait 8 minutes to have more than 90% extraction without TOA.
Dans le cas de la TLA, on prépare les emulsions suivantes :In the case of TLA, the following emulsions are prepared:
On constate que les résultats obtenus sont similaires : We note that the results obtained are similar:
3) Influence de la concentration du tensioactif3) Influence of the concentration of the surfactant
Pour déterminer l'influence de la concentration du tensioactif, on prépare les emulsions suivantes, contenant de la trilaurylamine (TLA) :To determine the influence of the concentration of the surfactant, the following emulsions are prepared, containing trilaurylamine (TLA):
On obtient les résultats suivants au bout de trois minutésThe following results are obtained after three minutes
La teneur optimale du tensioactif est donc de l'ordre de 3 à 5% d'Abil. De même, on prépare les emulsions suivantes, contenant de la trioctylamine (TOA) :The optimum content of the surfactant is therefore of the order of 3 to 5% of Abil. Likewise, the following emulsions, containing trioctylamine (TOA), are prepared:
On compare l'efficacité de l'extraction au bout de 2 minutes, et on obtient les résultats suivants :The efficiency of the extraction is compared after 2 minutes, and the following results are obtained:
L'optimum est moins net, mais existant, aux alentours de 7% d'Abil.The optimum is less clear, but existing, around 7% of Abil.
4) Influence de la quantité d'emulsion4) Influence of the amount of emulsion
Pour 100 mL de solution d'aspirine contenant 0,01 mol.L"1, différents volumes d'emulsion ont été utilisés : 15, 33 et 50 mL, ce qui correspond à des rapports volumiques de 6,5 ; 3 et 2.For 100 mL of aspirin solution containing 0.01 mol.L "1 , different volumes of emulsion were used: 15, 33 and 50 mL, which corresponds to volume ratios of 6.5, 3 and 2.
La composition de l'émulsion préparée est la suivante Dodécane : 47,1 % TOA : 0,9 % ABIL : 2 % NaOH 0,1 mol.L"1 : 50 % Les pourcentages d'extraction obtenus sont les suivantsThe composition of the emulsion prepared is as follows Dodecane: 47.1% TOA: 0.9% ABIL: 2% NaOH 0.1 mol.L "1 : 50% The extraction percentages obtained are as follows
Dans le cas du rapport 6,5, l'excès de soude est relativement faible ce qui peut expliquer le ralentissement du transfert. Ainsi, on a fait un essai avec le même rapport, mais avec de la soude à 0,16 mol.L"1. L'extraction devient quasi-totale en 8 minutes, mais elle est plus lente qu'avec des rapports volumiques plus faibles (aire interfaciale plus faible lors de l'extraction lorsque le rapport volumique augmente).In the case of the ratio 6.5, the excess sodium hydroxide is relatively small, which may explain the slowing of the transfer. Thus, we did a test with the same ratio, but with 0.16 mol.L "1 soda. The extraction becomes almost complete in 8 minutes, but it is slower than with more volume ratios. weak (lower interfacial area during extraction when the volume ratio increases).
Le tableau ci-après présente des exemples d'émulsions performantes, avec un rapport volumique égal à 2 :The table below presents examples of high-performance emulsions, with a volume ratio equal to 2:
Toutes ces emulsions révèlent un taux de rupture inférieur à 1 % au bout de 15 minutes d'agitation, attestant de leur stabilité au cours de leur utilisation. III - Généralisation et optimisation dans le cas des emulsions multiples (système II) :All these emulsions reveal a rupture rate of less than 1% after 15 minutes of agitation, attesting to their stability during use. III - Generalization and optimization in the case of multiple emulsions (system II):
La formule type retenue contient les composants suivants :The standard formula chosen contains the following components:
Emulsion primaire :Primary emulsion:
- Solvant organique apolaire : paraffine liquide (Primol 352)- Apolar organic solvent: liquid paraffin (Primol 352)
- Extractant organique : Trilaurylamine (C12H25)3N- Organic extractant: Trilaurylamine (C 12 H 25 ) 3 N
- Primol 352 + TLA : 30 %- Primol 352 + TLA: 30%
- Tensioactif : Cétyldiméthicone copolyol (Abil EM 90) : 6 %- Surfactant: Cetyldimethicone copolyol (Abil EM 90): 6%
- Agent piégeant : Soude- Trapping agent: Soda
- Electrolyte : Sulfate de magnésium (MgSO )- Electrolyte: Magnesium sulfate (MgSO)
Emulsion multiple :Multiple emulsion:
- tensioactif hydrophile : Arlatone F127G (copolymère d'oxyde d'éthylène et d'oxyde de propylène) : 1%- hydrophilic surfactant: Arlatone F127G (copolymer of ethylene oxide and propylene oxide): 1%
- emulsion primaire : 80% dans l'émulsion multiple- primary emulsion: 80% in the multiple emulsion
Ces constituants, ainsi que les valeurs indiquées des concentrations, ont été retenus en considérant les études menées avec les emulsions simples, dans la perspective de la capture de l'acide acétylsalicylique, ainsi que des résultats antérieurs obtenus sur la stabilité des emulsions multiples. Certaines modifications par rapport aux formules d'émulsions simples ont cependant été apportées, pour les raisons suivantes :These constituents, as well as the indicated values of the concentrations, were retained by considering the studies carried out with the simple emulsions, with a view to the capture of acetylsalicylic acid, as well as previous results obtained on the stability of multiple emulsions. Certain modifications compared to the formulas of simple emulsions were however made, for the following reasons:
Concernant le choix de l'huile, des études comparatives ont permis de montrer que l'efficacité d'extraction à travers la membrane lipidique était pratiquement inchangée pour la plupart des solvants. Cependant, une paraffine liquide a été préférée en raison de son innocuité bien connue par voie orale et de sa non-digestibilité. De même, le choix de l'extractant organique s'est porté sur la trilaurylamine en raison de sa moindre toxicité par voie orale.Regarding the choice of oil, comparative studies have shown that the extraction efficiency through the lipid membrane was practically unchanged for most solvents. However, a liquid paraffin was preferred because of its well-known oral safety and non-digestibility. Similarly, the choice of organic extractant fell on trilaurylamine because of its lower oral toxicity.
Un électrolyte (sulfate de magnésium) a d'autre part été introduit en phase aqueuse interne, pour stabiliser l'interface entre les microglobules aqueux et la phase organique. Des études antérieures menées sur les emulsions multiples ont en effet montré le rôle stabilisateur de certains électrolytes. Enfin, puisque le système contient deux interfaces, il a été nécessaire d'introduire un tensioactif hydrophile dans la phase aqueuse externe de l'émulsion multiple. La concentration de ce tensioactif a été fixée à 1 %, en raison d'études antérieures qui ont établi que cette valeur assurait une. stabilité maximale.An electrolyte (magnesium sulfate) was also introduced in the internal aqueous phase, to stabilize the interface between the aqueous microglobules and the phase organic. Previous studies carried out on multiple emulsions have indeed shown the stabilizing role of certain electrolytes. Finally, since the system contains two interfaces, it was necessary to introduce a hydrophilic surfactant into the external aqueous phase of the multiple emulsion. The concentration of this surfactant has been set at 1%, due to previous studies which have established that this value provides a. maximum stability.
A) Préparation des emulsions multiples :A) Preparation of multiple emulsions:
L'émulsion primaire est préparée en chauffant la phase aqueuse interne et la phase organique à 70-80°C à l'aide d'un bain-marie. La phase aqueuse est incorporée dans la phase huileuse sous une agitation vigoureuse de 3000 tpm à l'aide d'une turbine Rayneri de type centripète pendant 30 minutes. Ensuite, après refroidissement à température ambiante, l'émulsion primaire est introduite lentement dans la phase aqueuse externe. Cette seconde émulsification est assurée par la même turbine sous une agitation de 500 tpm. La durée d'agitation est fonction de la formulation et peut varier de 5 à 45 minutes.The primary emulsion is prepared by heating the internal aqueous phase and the organic phase to 70-80 ° C using a water bath. The aqueous phase is incorporated into the oily phase with vigorous stirring at 3000 rpm using a Rayneri centripetal turbine for 30 minutes. Then, after cooling to room temperature, the primary emulsion is slowly introduced into the external aqueous phase. This second emulsification is carried out by the same turbine with stirring of 500 rpm. The duration of agitation depends on the formulation and can vary from 5 to 45 minutes.
B) Etude de l'influence de la concentration de l'extractant, de l'agent piégeant et de l'électrolyte sur l'extraction in vitro de l'acide acétylsalicylique :B) Study of the influence of the concentration of the extractant, the trapping agent and the electrolyte on the in vitro extraction of acetylsalicylic acid:
On utilise la même procédure que pour le système I. On met en contact dans un bêcher, sous agitation mécanique, 10 mL d'emulsion avec 50 mL d'une solution aqueuse contenant 0,02 mol.L"1 d'aspirine ; on suit au cours du temps la concentration résiduelle de l'aspirine dans la phase aqueuse externe. On en déduit le pourcentage d'extraction, paramètre permettant la comparaison de l'efficacité des emulsions.The same procedure is used as for system I. 10 ml of emulsion is brought into contact in a beaker, with mechanical stirring, with 50 ml of an aqueous solution containing 0.02 mol.L "1 of aspirin; the residual concentration of aspirin in the external aqueous phase is monitored over time and the percentage of extraction is deduced therefrom, a parameter enabling the effectiveness of the emulsions to be compared.
De façon à obtenir une référence comparative, les taux d'extraction à différents temps ont d'abord été mesurés en utilisant une emulsion "blanche", ainsi dénommée parce qu'elle ne renferme aucun des constituants dont l'action est supposée être indispensable à une bonne extraction, à savoir les agents extractant et piégeant. La formule de cette emulsion blanche, ainsi que les taux d'extraction sont donnés par les tableaux ci-après (par la suite, les pourcentages sont calculés par rapport à l'émulsion primaire) :In order to obtain a comparative reference, the extraction rates at different times were first measured using a "white" emulsion, so called because it does not contain any of the constituents whose action is supposed to be essential to good extraction, namely extracting and trapping agents. The formula of this white emulsion, as well as the extraction rates are given by the tables below (thereafter, the percentages are calculated relative to the primary emulsion):
1) Influence de la concentration de l'agent piégeant (NaOH)1) Influence of the concentration of the trapping agent (NaOH)
On prépare 3 emulsions, différant seulement par leur concentration de NaOH3 emulsions are prepared, differing only in their NaOH concentration
On obtient les résultats suivants :The following results are obtained:
On observe donc une augmentation de l'efficacité d'extraction avec la concentration de l'agent piégeant, et cela même au-delà de la concentration 0,1 mol.L"1. Cela peut paraître surprenant puisque les résultats obtenus sur les emulsions simples avaient permis de montrer que le taux d'efficacité maximal était atteint à partir de 0,1 mol.L"1, concentration pour laquelle l'égalité de la concentration stœchiométrique OHVaspirine était obtenue. An increase in the extraction efficiency is therefore observed with the concentration of the trapping agent, and this even beyond the concentration 0.1 mol.L "1. This may seem surprising since the results obtained on the emulsions simple had shown that the maximum efficiency rate was reached from 0.1 mol.L "1 , concentration for which the equality of stoichiometric concentration OHVaspirin was obtained.
2) Influence de la concentration de l' électrolyte (MgSO )2) Influence of the electrolyte concentration (MgSO)
On prépare les 3 formules suivantes, qui diffèrent seulement par leur concentration de MgSO4 :The following 3 formulas are prepared, which differ only in their concentration of MgSO 4 :
On trouve ci-dessous le pourcentage d'extraction en fonction du temps pour les 3 emulsions :The extraction percentage as a function of time is given below for the 3 emulsions:
On observe que l'extraction est maximale pour une concentration de l' électrolyte de 2 %. Cependant, on note que le taux d'extraction reste encore relativement faible, bien qu'il soit significativement plus élevé que celui de l'émulsion blanche (45 %). 3) Influence de la concentration de l'extractant (TLA)It is observed that the extraction is maximum for a concentration of the electrolyte of 2%. However, we note that the extraction rate is still relatively low, although it is significantly higher than that of the white emulsion (45%). 3) Influence of the extractant concentration (TLA)
4 formules sont comparées, qui diffèrent seulement par leur concentration de4 formulas are compared, which differ only in their concentration of
TLAYOU'RE HERE
On trouve ci-dessous le pourcentage d'extraction en fonction du temps pour les 4 emulsions :The extraction percentage as a function of time is given below for the 4 emulsions:
De même qu'avec le système I, on observe que les performances sont très nettement supérieures lorsque l'extractant présente une concentration adaptée, non pas tant sur le plan de la vitesse d'extraction que de son efficacité. Alors que le taux d'extraction ne dépasse pas 65 % lorsque la concentration de TLA est de 0,3 %, il atteint des valeurs de l'ordre de 90 % lorsqu'elle est comprise entre 1 et 1,5 %. Il apparaît nettement que la concentration optimale est voisine de 1,5 %. Il est à noter qu'au-delà de 1,5 % de TLA, la stabilité de l'émulsion multiple diminue, ce qui entraîne une réduction de l'efficacité. Exemple d'emulsion multiple performante (rapport volumique 2)As with system I, it is observed that the performances are very clearly superior when the extractant has an appropriate concentration, not so much in terms of the extraction speed as in its efficiency. While the extraction rate does not exceed 65% when the TLA concentration is 0.3%, it reaches values of the order of 90% when it is between 1 and 1.5%. It clearly appears that the optimal concentration is close to 1.5%. It should be noted that above 1.5% of TLA, the stability of the multiple emulsion decreases, which leads to a reduction in efficiency. Example of a high performance multiple emulsion (volume ratio 2)
Puisque l' administration orale est envisagée, il est évidemment essentiel de s'assurer que les systèmes émulsionnés considérés conserveront leur stabilité en milieu gastrique et intestinal. Des études in vitro portant sur des emulsions multiples blanches (en absence d'un couple extractant et piégeant) dans des phases aqueuses présentant la même composition que les milieux gastrique et intestinal, ont d'ores et déjà démontré une remarquable stabilité vis à vis des enzymes digestives.Since oral administration is envisaged, it is obviously essential to ensure that the emulsified systems considered will maintain their stability in the gastric and intestinal medium. In vitro studies on multiple white emulsions (in the absence of an extracting and trapping couple) in aqueous phases having the same composition as the gastric and intestinal mediums, have already demonstrated remarkable stability with respect to digestive enzymes.
EXEMPLE DU PARACETAMOLEXAMPLE OF PARACETAMOL
Pour des molécules toxiques à caractère acido-basique très faible (alcool, glycol ; paracétamol par exemple), on envisagera un transporteur solvatant et une phase aqueuse interne capable de réagir avec le toxique pour le piéger sous une forme lipophobe (oxydant, base forte...).For very weak acid-base toxic molecules (alcohol, glycol; paracetamol for example), a solvating transporter and an internal aqueous phase capable of reacting with the toxic agent to trap it in a lipophobic form (oxidant, strong base) will be considered. ..).
Des expériences ont été effectuées dans le cadré de la détoxication du paracétamol.Experiments were carried out as part of the detoxification of paracetamol.
L'émulsion suivante a été préparéeThe following emulsion has been prepared
phase organique octanol : 20%octanol organic phase: 20%
ECA 4360 (tensioactif) : 3% dodécane qsp phase aqueuse interneECA 4360 (surfactant): 3% dodecane qs internal aqueous phase
NaOH 0,5 molX"1 0.5 molX NaOH "1
On obtient une efficacité d'extraction de 80%o en moins de 5 minutes.An extraction efficiency of 80% is obtained in less than 5 minutes.
EXEMPLE DE LA ZOPICLONEZOPICLONE EXAMPLE
Des systèmes symétriques sont envisagés pour extraire des toxiques à caractère basique en utilisant comme transporteur une molécule organique acide (acide organophosphoré, acide carboxylique) très peu soluble dans l'eau ; la solution aqueuse interne sera une solution acide.Symmetrical systems are envisaged for extracting toxic substances of a basic nature by using as carrier a acid organic molecule (organophosphorus acid, carboxylic acid) very poorly soluble in water; the internal aqueous solution will be an acid solution.
Les réactions mises enjeu seront les suivantes ; par exemple pour l'ammoniaque :The reactions involved will be as follows; for example for ammonia:
1èr6 interface : NH3aq + HRorg <- N-FXRorg1 èr6 interface: NH 3aq + HRo rg <- N-FXRorg
2ème interface : NH4R0rg+ 11 <-» HRorg + NH4 + aq 2nd interface: NH 4 R 0rg + 11 <- »HR org + NH 4 + aq
Des expériences ont été effectuées dans le cadre de la détoxication de la zopiclone, qui est une molécule à caractère basique.Experiments have been carried out in the context of the detoxification of zopiclone, which is a molecule with a basic character.
L'émulsion suivante a été préparée :The following emulsion was prepared:
phase organiqueorganic phase
Cyanex 302 : 2% ,'Cyanex 302: 2%, '
EGA 4360 (tensioactif) : 10% dodécane qspEGA 4360 (surfactant): 10% dodecane qs
phase aqueuse interne HC1 1 molX"1 internal aqueous phase HC1 1 molX "1
On obtient une efficacité d'extraction de 90% en 5 minutes. An extraction efficiency of 90% is obtained in 5 minutes.
Claims
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| FR0206849A FR2840218B1 (en) | 2002-06-04 | 2002-06-04 | SINGLE AND MULTIPLE EMULSIONS FOR DETOXICATION OF THE ORGANISM OR SURFACES |
| FR0206849 | 2002-06-04 | ||
| PCT/FR2003/001674 WO2003101426A2 (en) | 2002-06-04 | 2003-06-04 | Simple and multiple emulsions for decontamination of an organism or surfaces |
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| US3934007A (en) * | 1973-06-25 | 1976-01-20 | American Cyanamid Company | Method of removing toxic substances from the intestinal tract by the use of a surfactant and a sorbent |
| CA1045976A (en) * | 1974-05-02 | 1979-01-09 | William J. Asher | Liquid membrane encapsulated medicinals and uses thereof |
| US4259318A (en) * | 1978-03-02 | 1981-03-31 | University Of Houston, Central Campus | Poison ivy relief composition |
| FR2419730A1 (en) * | 1978-03-13 | 1979-10-12 | Armines | Selective purificn. of body fluid contg. toxic prods. - using liq. membranes in emulsion |
| US4191812A (en) * | 1978-09-19 | 1980-03-04 | Rohm And Haas Company | Ion exchange process involving emulsion ion exchange resins |
| US4806354A (en) * | 1984-04-06 | 1989-02-21 | Green James P | Health food composition |
| EP0236883B1 (en) * | 1986-03-06 | 1992-06-03 | Odenwaldwerke Rittersbach GmbH Fahrzeugbau und Katastrophenschutzsysteme | Device for producing a detoxicating emulsion for combat agents |
| DE3638625A1 (en) * | 1986-11-12 | 1988-05-26 | Bundesrep Deutschland | Detoxifying emulsion and process, apparatus and check on results for preparation of the emulsion |
| FR2761607A1 (en) * | 1997-04-04 | 1998-10-09 | Boots Co Plc | DERMATOLOGICAL COMPOSITION FOR THE TREATMENT OF SKIN AGING SYMPTOMS |
| WO2002076392A2 (en) * | 2001-03-21 | 2002-10-03 | Madash Llc | Thermally reversible water in oil in water emulsions |
-
2002
- 2002-06-04 FR FR0206849A patent/FR2840218B1/en not_active Expired - Fee Related
-
2003
- 2003-06-04 EP EP03756050A patent/EP1513501A2/en not_active Withdrawn
- 2003-06-04 US US10/516,914 patent/US20050244438A1/en not_active Abandoned
- 2003-06-04 AU AU2003255635A patent/AU2003255635A1/en not_active Abandoned
- 2003-06-04 WO PCT/FR2003/001674 patent/WO2003101426A2/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO03101426A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003255635A1 (en) | 2003-12-19 |
| FR2840218A1 (en) | 2003-12-05 |
| US20050244438A1 (en) | 2005-11-03 |
| FR2840218B1 (en) | 2004-08-13 |
| WO2003101426A2 (en) | 2003-12-11 |
| AU2003255635A8 (en) | 2003-12-19 |
| WO2003101426A3 (en) | 2004-04-08 |
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