EP0147428A1 - Capsules vaginales - Google Patents
Capsules vaginalesInfo
- Publication number
- EP0147428A1 EP0147428A1 EP84902197A EP84902197A EP0147428A1 EP 0147428 A1 EP0147428 A1 EP 0147428A1 EP 84902197 A EP84902197 A EP 84902197A EP 84902197 A EP84902197 A EP 84902197A EP 0147428 A1 EP0147428 A1 EP 0147428A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- capsule
- starch
- viscosity
- oil
- capsule according
- 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- Withdrawn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
- 239000002775 capsule Substances 0.000 title claims abstract description 116
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 69
- 241000894006 Bacteria Species 0.000 claims abstract description 48
- 239000012141 concentrate Substances 0.000 claims abstract description 38
- 240000001046 Lactobacillus acidophilus Species 0.000 claims abstract description 35
- 239000004310 lactic acid Substances 0.000 claims abstract description 35
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 35
- 229920002472 Starch Polymers 0.000 claims abstract description 26
- 235000019698 starch Nutrition 0.000 claims abstract description 26
- 239000008107 starch Substances 0.000 claims abstract description 26
- 230000000694 effects Effects 0.000 claims abstract description 25
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 23
- 239000012530 fluid Substances 0.000 claims abstract description 23
- 230000001580 bacterial effect Effects 0.000 claims abstract description 21
- 239000007903 gelatin capsule Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 27
- 239000003921 oil Substances 0.000 claims description 27
- 235000019198 oils Nutrition 0.000 claims description 27
- 229920002261 Corn starch Polymers 0.000 claims description 26
- 239000008120 corn starch Substances 0.000 claims description 26
- 206010046914 Vaginal infection Diseases 0.000 claims description 20
- 229940099259 vaseline Drugs 0.000 claims description 17
- 239000005662 Paraffin oil Substances 0.000 claims description 16
- 235000019486 Sunflower oil Nutrition 0.000 claims description 15
- 239000002600 sunflower oil Substances 0.000 claims description 15
- KKEBXNMGHUCPEZ-UHFFFAOYSA-N 4-phenyl-1-(2-sulfanylethyl)imidazolidin-2-one Chemical compound N1C(=O)N(CCS)CC1C1=CC=CC=C1 KKEBXNMGHUCPEZ-UHFFFAOYSA-N 0.000 claims description 8
- 244000199885 Lactobacillus bulgaricus Species 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 241000194020 Streptococcus thermophilus Species 0.000 claims description 6
- 239000004615 ingredient Substances 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 241000894007 species Species 0.000 claims description 6
- 241000186660 Lactobacillus Species 0.000 claims description 5
- 239000004698 Polyethylene Substances 0.000 claims description 5
- 150000001720 carbohydrates Chemical class 0.000 claims description 5
- 235000014633 carbohydrates Nutrition 0.000 claims description 5
- 238000011049 filling Methods 0.000 claims description 5
- -1 polyethylene Polymers 0.000 claims description 5
- 229920000573 polyethylene Polymers 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 241000194017 Streptococcus Species 0.000 claims description 4
- 150000001719 carbohydrate derivatives Chemical class 0.000 claims description 4
- 229940039696 lactobacillus Drugs 0.000 claims description 4
- 238000007789 sealing Methods 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 241001603151 Philus Species 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 244000057717 Streptococcus lactis Species 0.000 claims description 3
- 229910021536 Zeolite Inorganic materials 0.000 claims description 3
- 239000000440 bentonite Substances 0.000 claims description 3
- 229910000278 bentonite Inorganic materials 0.000 claims description 3
- 235000012216 bentonite Nutrition 0.000 claims description 3
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims description 3
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims description 3
- 239000006185 dispersion Substances 0.000 claims description 3
- 229910021485 fumed silica Inorganic materials 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000002480 mineral oil Substances 0.000 claims description 3
- 235000019426 modified starch Nutrition 0.000 claims description 3
- 239000000454 talc Substances 0.000 claims description 3
- 229910052623 talc Inorganic materials 0.000 claims description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 3
- 239000008158 vegetable oil Substances 0.000 claims description 3
- 239000010457 zeolite Substances 0.000 claims description 3
- 244000199866 Lactobacillus casei Species 0.000 claims description 2
- 241000186673 Lactobacillus delbrueckii Species 0.000 claims description 2
- 241000186840 Lactobacillus fermentum Species 0.000 claims description 2
- 240000006024 Lactobacillus plantarum Species 0.000 claims description 2
- 241000166315 Vulcaniibacterium thermophilum Species 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 235000010446 mineral oil Nutrition 0.000 claims 2
- 241000193830 Bacillus <bacterium> Species 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 240000002605 Lactobacillus helveticus Species 0.000 claims 1
- 241001674646 Lepeophtheirus bifidus Species 0.000 claims 1
- 241000222122 Candida albicans Species 0.000 abstract description 15
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 229940039695 lactobacillus acidophilus Drugs 0.000 abstract description 6
- 229940095731 candida albicans Drugs 0.000 abstract description 5
- 208000015181 infectious disease Diseases 0.000 abstract description 5
- 238000000338 in vitro Methods 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 2
- 239000004264 Petrolatum Substances 0.000 abstract 1
- 238000010790 dilution Methods 0.000 abstract 1
- 239000012895 dilution Substances 0.000 abstract 1
- 229940066842 petrolatum Drugs 0.000 abstract 1
- 235000019271 petrolatum Nutrition 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 229940099112 cornstarch Drugs 0.000 description 24
- 210000001215 vagina Anatomy 0.000 description 20
- 241000501458 Cultus Species 0.000 description 15
- 229940032147 starch Drugs 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 8
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 7
- 238000009826 distribution Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 244000005700 microbiome Species 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000035899 viability Effects 0.000 description 6
- 235000010633 broth Nutrition 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000004062 sedimentation Methods 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 239000000969 carrier Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 210000004877 mucosa Anatomy 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 230000000306 recurrent effect Effects 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 201000008100 Vaginitis Diseases 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000004599 antimicrobial Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 244000000010 microbial pathogen Species 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 235000013960 Lactobacillus bulgaricus Nutrition 0.000 description 2
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000224526 Trichomonas Species 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000001332 colony forming effect Effects 0.000 description 2
- 235000013365 dairy product Nutrition 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 229940004208 lactobacillus bulgaricus Drugs 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000007493 shaping process Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 241000207202 Gardnerella Species 0.000 description 1
- 108010010803 Gelatin Proteins 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
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- 241000194034 Lactococcus lactis subsp. cremoris Species 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 241000364057 Peoria Species 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241001478215 Sphingobacterium faecium Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 108010038836 acidolin Proteins 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SMDHCQAYESWHAE-UHFFFAOYSA-N benfluralin Chemical compound CCCCN(CC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O SMDHCQAYESWHAE-UHFFFAOYSA-N 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000010909 chemical acidification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 235000014048 cultured milk product Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
- 229960001348 estriol Drugs 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 239000004407 iron oxides and hydroxides Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000020442 loss of weight Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000003821 menstrual periods Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005706 microflora Species 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 239000004223 monosodium glutamate Substances 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 description 1
- 235000019982 sodium hexametaphosphate Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 235000019832 sodium triphosphate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Definitions
- the present invention relates to a method and a capsule for control ⁇ ling vulvo-vaginal infections .
- antibiotic treatment has proved to be disadvantageous as antibiotics tend to kill the desi red microflora in the vagina as well, whereby the natu ral healthy microbial balance of the vagina is disturbed . This in turn often results in the condition becoming re-occurring as the pathogenic microorganisms often re-in ⁇ vade the vaginal environment without other microorganisms to check their growth .
- a more preferred way of controlling vulvo-vaginal infections is to employ lactic acid bacteria so as to simulate the normal vaginal envi- ronment.
- infections occu r when the pH of the vagina is too high such as at menstruation, or when the hor ⁇ monal balance is disturbed because of pregnancy or when taking oral contraceptives, thus promoting the growth of potentially pathogenic microorganisms such as Candida albicans, Trichomon ⁇ s vaginalis, Staphyfococcus aureus, Gardnerella, - Streptococci and various anaer ⁇ obic microorganisms which, conversely, were not assumed to th rive under the normal, slightly acidic conditions in the vagina .
- pathogenic microorganisms such as Candida albicans, Trichomon ⁇ s vaginalis, Staphyfococcus aureus, Gardnerella, - Streptococci and various anaer ⁇ obic microorganisms which, conversely, were
- lactic acid bacteria In the known use of lactic acid bacteria, either a fermented milk product containing Lactobaciili is introduced manually, or a slurry of dried Lactobacillus acidophilus (e.g . the product known as Floranorm, marketed by Danapharm) is introduced by means of a suitable applica ⁇ tor such as a disposable syringe.
- a suitable applica ⁇ tor such as a disposable syringe.
- the non-encapsuled products suffer from the disadvantage that their application is uneven, i . e. the distribution of the lactic acid bacteria in the vagina is not homogeneous .
- the application me- thod may also be found to be inconvenient.
- the products are rather fluid, they tend to run out of the vagina so that they do not have the desired effect.
- a disadvantage of the product known from US Patent No. 3.639.566 is that the bacteria incorporated in the capsules are likely to have a limited stability, due to the content of moisture absorbed by the starch incorporated in the capsule so that the capsules may only be stored for limited periods of time. Further ⁇ more, when applied in the vagina, the capsule wilt take up moisture for which reason the capsule content tends to get lumpy; this may result in an uneven distribution over the vaginal area and probably a reduced effect.
- the present invention provides capsules which are superior with respect to efficient introduction and distribution of an effective a- mount of lactic acid bacteria into the vagina, and correspondingly provides an efficient method for controlling vulvo-vaginal infections .
- the capsules of the invention are improved over the known art by containing stabilized cells of lactic acid bacteria, which means that they may be stored at room temperature for several months while maintaining a high percentage of viability.
- one aspect of the invention relates to a soluble capsule for controlling vulvo-vaginal infections which contains a stable, dried, viable concentrate of lactic acid bacteria dispersed in a pharmaceuti ⁇ cally acceptable fluid carrier.
- the term “dried” indicates that the concen ⁇ trate has a water activity (a ) of not more than 0.2, calculated w according to the formula described by e. g . D . Demeyer, Fleischwirt- schaft 59(7) , 1979, p. 940.
- the capsule is preferably a gelatin capsule, in particular a soft gelatin capsule.
- the capsule may, however, also be a hard, but soluble gelatin capsule.
- the capsule may be of any suitable shape such as a spherical or oblong shape, but for easy application it is preferred that the capsule be oval or egg-shaped .
- the volume of the capsule is in the range of about 0.2-5.0, preferably about 1 .2 ml .
- the capsule volume is in fact rather critical as the physical proper ⁇ ties of the paste vide below) set limits to the amount of paste mate ⁇ rial and thus the amount of bacteria per capsule which may adhere or be adsorbed to the vaginal mucosa without causing any significant discharge problems .
- the capsules preferred for use according to the invention are those produced substantially according to the disclosu re of US Patents Nos . 1 ,970,396, 2, 152, 101 , 2,234,479 and 2, 288,327.
- the count of viable lactic acid bacteria is at least 1 x 10 s , preferably at least 1 10 7 , more - preferably at least 1 x 10 s and most preferably in the range between about 1 10 9 and 1 10 11 , such as about 1 x 10 9 and 1 10 l ⁇ per capsule.
- the dried, stabilized bacterial concentrate when incorporated in the capsules of the invention, is not totally moisture-free, but contains some internal moisture. I n order to obtain a stable, dried concentrate with such a high cell count of viable bacteria, it is, however, desi ⁇ rable that the water activity of the concentrate is in the range of 0.00-0.2, preferably in the range of 0.00-0.1 .
- a suitable instrument for determining water activity is available from Novasima AG, Zurich, Switzerland .
- the concentrate is mixed with a fluid car- rier.
- a fluid car- rier it has been found that particular types of fluid carrier are extremely well suited both for an even distribution in the vagina and for maintaining a high stability (i . e. long-term viability) of the concentrate.
- the carrier is thus primarily so selected that it will protect the freeze-dried bacterial culture from physical and/or chemical reactions which have a negative effect on cell stability (expressed as a loss of viability) . It has been found that the most important single factor for maintaining the stability of the concentrate is the low water activity of the culture/carrier mixture for the reasons stated above.
- the carrier should also have a water activity in the range of 0.00-0.2, preferably 0.00-0.1 .
- the carrier is preferably a non-hygroscopic carrier to substantially prevent water uptake th rough the capsule wall which would decrease bacterial stability.
- the fluid carrier should also be one which secures a homogeneous distribution of the bacteria in the vagina and an optimal contact with the vaginal mucosa upon the release of the carrier from the partly- dissolved capsule but which, on the other hand, does not cause the carrier material to run from the vagina immediately after application .
- a carrier containing a bacterial concentrate has a certain thixotropicity, i . e.
- the viscosity of the carrier within the capsule is sufficiently high to ensu re that there is little movement of the carrier during handling or transportation of the capsules, thereby avoiding any movement of the dried concentrate which might increase the exposu re of the concentrate to the inner capsule wall and thus increase the possibility that the cultu re might receive moistu re from the su rroundings .
- This emphasis on a certain viscosity of the fluid carrier distinguishes the capsule of the inven ⁇ tion from capsules intended for oral administration , which contain lactic acid bacteria in a fluid carrier (e. g .
- LactofloraTM marketed by Camette ApS, Esbjerg, Denmark
- the fluid carrier in the known capsules does not have a sufficient viscosity to prevent sedimentation of the bacteria and possible uptake of moisture so that cell stability is likely to be impai red .
- the capsule of the invention should contain a fluid car ⁇ rier with a viscosity of at least 2000 cps at a temperatu re of 20°C, as this viscosity is sufficient to secu re a satisfactory cell stability, while not being too high to prevent a "melting down" in the vagina to ob- tain a sufficiently low viscosity at the vaginal temperature for the above-mentioned homogeneous distribution to take place.
- the carrier has a viscosity of at least 3000 cps, in particular at least 4000 cps at 20°C, it will still have a behaviou r with respect to consistency which is very well suited for effective distribu ⁇ tion of the bacterial culture under the conditions prevailing in the vagina .
- a capsule containing such a carrier with a concentrate of lactic acid bacteria may suitably be administered when the patient goes to bed.
- the capsule will disintegrate to such an extent that it releases its carrier content which is then distributed in the vagina, causing an even distribution of the concentrate of viable lactic acid bacteria which adhere to the vaginal wall and, in the conditions prevailing in the vagina, such as temperature and moisture, will become biologically active and multiply.
- any remainder of the carrier will tend to leave the vagina, but will not give rise to noteworthy discomfort.
- the fluid carrier is a sub ⁇ stantially anhydrous paste preferably comprising a substantially non- hygroscopic oil which is either inherently of a suitable viscosity, e.g . comprises a mixture of oil and fat, such as cocoa butter, or which may include a particulate or dissolved or polymeric viscosity-increasing agent to obtain a suitable viscosity.
- a suitable viscosity e.g . comprises a mixture of oil and fat, such as cocoa butter, or which may include a particulate or dissolved or polymeric viscosity-increasing agent to obtain a suitable viscosity.
- the viscosity-increasing agent may be selected from solid or semi- solid hydrocarbons capable of forming a homogeneous system with the oil, such as vaseline or polyethylene, particulate inorganic substances such as fumed silica, talc, zeolite or bentonite, and carbohydrates or carbohydrate derivatives, preferably high molecular weight carbo ⁇ hydrates such as starch and starch derivatives . It is, however, believed to be necessary that the viscosity-increasing agents employed should have as low a water activity as possible; preferably the a does not exceed 0.1 . This means that the viscosity-increasing agent should have a certain , but limited hygroscopicity .
- an oil and corn starch mixtu re is the preferred carrier because it has been found that there is a synergism between a sub ⁇ stantially anhydrous oil and corn starch with respect to preserving the viability of lactic acid bacteria .
- the synergism is a combined effect of 1 ) the fact that the corn starch (which is prefe ⁇ rably in a freeze-dried or dehydrated form prior to its incorporation in the oil so as to have a water activity of almost 0: 00) has a balan ⁇ ced water activity which tends to attract water from the oil in the final system, thus competing with the dried bacterial cultu re (which is very hygroscopic in the freeze-dried state) which will also have a tendency to absorb any small amount of free water present in the oil, and 2) the starch such as corn sta rch in particular may have an inherent stabilizing effect on lactic acid bacteria .
- the starch may advantageously be admixed with vaseline in an amount of about 10-50% by weight of the starch .
- a combination of a sub- stantially anhydrous oil and the starch such as corn starch or, especially, the starch/vaseline mixtu re, e. g . a weight ratio in the range from about 2: 5 to about 5: 2, preferably about 1 : 1 , has been found to be a most suitable carrier for efficiently intravaginal ly administering lactic acid bacteria .
- useful oils may be mentioned mineral or vegetable oils such as paraffin or sunflower oil .
- the lactic acid bacteria concentrate incorporated in the capsules according to the invention may be comprised of any type of bacteria which produce lactic acid, such as bacteria belonging to the genus Streptococcus or Lactobacillus .
- the species of Lactobacillus employed according to the invention are principally L . acidophilus, L . bulgari- cus, L . lactls, L . hefveticus, L . bifid us, L . casei , L. plantarum, L. delbrueckii , L . thermophilus or L . fermentum.
- Preferred among Streptococcus species are S. lactis, S. cremoris, S. diacetylactis, S. thermophilus or S.
- the lactic acid bacteria may also be incorporated in the form of a mixture of two or more of these species . Lactic acid bacteria of the species L . acidophilus have proved particu ⁇ larly advantageous . The strain of L . acidophilus which has proved to be particularly advantageous has been deposited in the Northern Regional Research Center, Peoria, USA under the accession number NRRL No. B-15260 and is publicly available.
- the conditions treated by administering the capsule according to the invention are vulvo-vaginal infections caused by, i . a . , microorganisms such as Candida alb leans, Trichomonas vaginal is and Staphylococcus aureus as well as various anaerobic microorganisms .
- the capsule of the invention has been found to be particularly advantageous in the treatment of recurrent vulvo-vaginal infections which has hitherto been difficult to cu re with conventional preparations such as anti ⁇ biotics.
- a particularly advantageous species of lactic acid bacteria is L . acidophilus, as described in Example 5. The superior qualities of L .
- acidophilus are most likely due to the fact that this species not only produces lactic acid (a decrease of pH is often not enough to control or reduce the growth of pathogenic micro ⁇ organisms) , but has also been found to produce one or more antimi ⁇ crobial metabolites described as acidophilin r vide e. g. Shahani, K. M. et al : "Natural Antibiotic Activity of Lactobacillus acidophilus and bulgaricus. 2. Isolation of Acidophilin from L, acidophilus” , Cult. Dairy Prod. J. 12, 1977, p. 8. ) , acidolin Cvide e. g . "Lactobacillus acidophilus I I . Antimicrobial agents. Cult.
- vulvo-vaginal infections may suitably be treated by administering 1 -2 capsules a day for 3-6 days, or a similar dosage may be administered prophylactically for a few days after each men-
- a suitable dosage in more severe cases may be 1 capsule a day until the first menstrual period, and for a 7-day period after each menstruation .
- the capsule may be inserted with the fingers or by means of a suitable applicator.
- the capsules may be produced by homogeneously dispersing a dried, viable, stable culture of lactic acid bacteria in a substantially an ⁇ hydrous fluid carrier, filling the resulting dispersion into soft gelatin capsules and drying the capsules after sealing.
- the paste in order to make the mixing of the ingredients re- latively easy, especially if the paste is to include a viscosity-in ⁇ creasing agent, it is preferred to add the culture to the paste ingre ⁇ washer which has the lowest viscosity followed by adding the viscosi ⁇ ty-increasing agent in the form of other dry matter or optionally a more highly viscous ingredient.
- This proceedu re saves time which is vital with respect to the amount of moisture taken up by the cultu re from the air.
- an inert and dry gas may be exposed to the mixing su rface.
- the admixture of the cultu re and optionally other dry matter and the oil may, for instance, be performed by means of a slowly operating mixer. I n this way, the uptake of air in the mixtu re is minimized, thus minimizing the risk of uptake of moistu re and oxygen which are detrimental to bacterial stability . I n order to fu rther reduce the moisture content of the final product, the ingredients are incorpo ⁇ rated in the oil in a dry state.
- the freeze-dried bacterial concentrate has a water activity not exceeding 0.2 and preferably a far lower water activity, and when the viscosity-increasing agent employed is a starch such as corn starch , it is preferably subjected to freeze-drying prior to use, substantially to a water activity of 0.00.
- a finely dispersed and homogeneous product is not obtained by merely mixing the ingredients as described above, and is provided e. g . by dispersing the cultu re by means of a roller mill operating at the pressu re and friction by which a fi ne division of the bacterial
- OMPI culture is secured without, on the other hand, heating the paste or killing the bacteria .
- the space between the rollers will normally be between 150 and 300 ⁇ m.
- the resulting particle size will be about 100 urn.
- the paste is gently stirred in order to impart homogeneity to the paste which is important to obtain in order to make it possible to dose accurate amounts of bacteria into each capsule.
- the paste is then incorporated in gelatin capsules, preferably soft gelatin capsules, by a process described in US Patents Nos . 1 ,970,396, 2, 152, 101 , 2,234,479 and 2,288,327.
- the capsules may be washed with an agent which prevents intercapsular adhesion, such as perchloroethylene, to which a lubricant such as lecithin has optionally been added whereby intercapsular adhesion and deformation of the capsules during the subsequent drying process are avoided .
- the drying itself may be performed in a two-stage process .
- the still wet capsules may be subjected to a strong air-flow, normally with ordinary atmospheric air with a relative humidity of about 20-60%.
- a strong air-flow normally with ordinary atmospheric air with a relative humidity of about 20-60%.
- the drying is continued on trays with ventilation for up to several days until the desired hardness and loss of humidity have been obtained .
- the final product is preferably stored at a temperature below 20°C, such as at a refrigeration temperature of about 3-5°C.
- a dry, stable, viable concentrate of L. acidophilus was prepared according to the procedures described in US Patents Nos. 4,115,199 and 3,897,307.
- the strain of L. acidophilus used is deposited with the Northern Regional Research Center and is publicly available under the accession number NRRL No. B-15260.
- the bacterial concentrate was dried by freeze-drying after adjusting the pH to 6.0-6.2, and the addition of 16 g L-ascorbic acid, 10 g inositol and 10 g monoso- dium glutamate per 100 g of the dry concentrate.
- the resulting stabilized, dry concentrate contains about 1.00 x 10 11 CFU (colony- forming units) per gramme.
- compositions stated below were prepared according to the method described above with the exception of composition C.
- the amount of paste material varies according to the desired number of cells in the finished capsules and thus the amount of bacterial con ⁇ centrate incorporated, in order to obtain the desired viscosity.
- Composition A A:
- Paraffin oil of low viscosity 1 5.5 kg Freeze-dried corn starch CPC 3401 4.5 kg Freeze-dried L. acidophilus culture (1.05 x 10 1X CFU/g) 1.0 kg
- VflPO This composition is presently preferred .
- Composition B
- Paraffin oil of low viscosity 1 7.0 kg yellow vaseline 2 6.0 kg L . acidophilus culture
- Composition C is a composition having Composition C:
- the carrier for the bacterial cultu re has as low an uptake of water as possible, and pre ⁇ ferably no uptake of water at all .
- hygroscopicity analyses were made of the following mate ⁇ rials and mixtures of materials as shown in Table 1 .
- the materials were spread on petri dishes with a diameter of 9 cm, and a thickness of the material of 7-8 mm, the materials having a substantially smooth surface.
- Sunflower oil Commercial edible oil purchased from Irma. Corn starch Globe® 03401 purchased from CPC, freeze-dried to an A of 0.00. w
- Vaseline Vaselinum Ph. Nord. 63 purchased from Meco ⁇ benzon.
- the "white" star indicates the L . acidophilus culture alone
- the square with the filled-in ci rcle indicates oil and viscosity- increasing agent (paraffin oil and corn starch in Fig . 1 , sunflower oil and corn starch in Fig . 2, paraffin oil and vaseline in Fig . 3)
- the square indicates the viscosity-increasing agent alone (corn starch in Figs . 1 and 2, vaseline in Fig . 3)
- the filled-in ci rcle indicates the oil (paraffin oil in Figs . 1 and 3)
- the filled-in star indicates "Plastibase” (as defined above)
- "log CFU” indicates the logarithm of colony-forming units per gramme of carrier.
- the curves may be compared among themselves, especially with respect to the slope of the first, straight line and "breakpoint" (45°) , i. e. the temperature at which the curve changes its course (usually at 59-60°C for cultures with a satisfactory stability; indicated by the dotted line in Figs . 1 -3) .
- the capsules have a half life of about 4 months at 20°C at which time the capsules still contain an effective amount of bacteria . Due to the improved storability at 5°C, it is, however, preferred that the capsules be stored at about 5°C or less .
- Soft gelatin capsules were prepared according to US Patents Nos . 1 ,970,396, 2, 152, 101 , 2,234,479 and 2,288,327.
- the capsule material may vary in composition within certain limits .
- the composition pre ⁇ ferred for the present purpose is shown in Table 3.
- the capsules After shaping the capsules and filling them with the dispersion of bacterial cultu re incorporated in the paste and sealing, the capsules were washed in perchloroethylene to which had been added a limited amount of lecithin in order to avoid intercapsular adhesion and defor ⁇ mation of the capsules during drying .
- the capsules were dried for 2 hours in a rotary drier with 6-8 com ⁇ partments by a strong ai r-flow with ordinary atmospheric air with a relative humidity of about 20%. I n this manner, the capsules were dried to an extent corresponding to a loss of weight of about 40-45%. The capsules had then become sufficiently hard for continued drying
- OMPI sy wipo to be performed on trays in a closed, ventilated cupboard at about 20°C (relative humidity 20%) for up to 4-6 days, until a suitable hardness and dessication had been obtained.
- Each of the strains was inoculated in growth flasks with 100 ml MRS- broth to a cell count of 1 -5 x 10 s CFU/ml .
- To some of these flasks as well as to some flasks which had not previously been inoculated were simultaneously added one of two cultu res of Candida albicans which were freshly grown from women with yeast infections (vulvo-vaginal infections) .
- MRS-broth was inoculated with L . acidophi ⁇ lus in an amount of 5 x 10 s CFU/ml and incubated at 37°C for 24 hours after which the living cells were centrifugated off and the supernatant were finally filtered under sterile conditions .
- the final pH was 4.18.
- This broth was inoculated with one of the Candida cultures . All flasks were incubated at 37°C, and the broths were plated for the specific microorganism after 0 hours, 24 hours and 48 hours
- the dotted lines represent the growth of L. acido ⁇ philus (expressed as cell count), the filled-in star indicating the growth of L. acidophilus when grown alone, and the square indicating the growth of L. acidophilus when grown together with C. albicans (two different strains in 4 a and 4 b). It appears that the growth of L. acidophilus. is not inhibited by the presence of Candida.
- the full lines represent the growth of C. albicans, the "white” star indicating the growth of Candida when grown alone, and the circle indicating the growth of Candida when grown together with L. acidophilus. It appears that both Candida cultures are significantly inhibited (ap- prox. 4 log,,, units) when inoculated together with the L. acidophilus strain used.
- Figs. 5 and 6 are analogous with Fig. 4 with the exception that Fig. 5 shows the use of L. bulgaricus and Fig. 6 the use of S. thermo ⁇ philus instead of L. acidophilus. From the graphs, it appears that neither L. bulgaricus nor S. thermophilus (the dotted lines) are inhibited by the growth of C. albicans. It appears from Fig. 5 that there is a slight inhibition of C. albicans when grown together with L. bulgaricus. From Fig. 6 it appears that S. thermophilus does not exert any inhibitory effect against C. albicans.
- Fig. 7 shows that, when a broth is acidified (to a pH of 4.18 by means of the selected strain of L. acidophilus) and physically sterili ⁇ zed as described above, the C. albicans culture (indicated by the "white” circle) cannot tolerate the concentration of the antimicrobial metabolites, i.e. the cell counts drop during the first 24 hours peri- od.
- the growth of C. albicans in normal broth is indicated by the filled-in circle.
- a chemical acidification of MRS-broth with lactic and phosphoric acid to a pH 4-4.2 has no influence, or only very little influence, on the growth of C. albicans.
- the study was performed at the dermatological clinic of Odense Sygehus, Denmark, involving 8 women of ages between 18 and 30 years (23 years on average) suffering from vulvo-vaginal infections, who had been referred to the clinic for treatment.
- the test comprised administering one capsule twice daily for 7 days so that four of the patients received the capsule of the invention and four of the patients received a placebo capsule used as control.
- a subjec ⁇ tive as well as objective evaluation of the condition of the patients was carried out, comparing it to their condition before treatment.
- the criteria of evaluation were: recovery (scored as 1), improvement (2), no change (3), and deterioration (4).
- the capsule according to the invention was administered once a day for 2-6 months (4 months on average) .
- the capsule of the invention is also useful in the treatment of women suffering from severe, ch ronic or recurrent vaginitis .
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Abstract
Des capsules de gélatine solubles pour effectuer la régulation d'infections vulvo-vaginales contiennent un concentré viable, séché, stable, tel qu'un concentré lyophilisé, de bactéries d'acide lactique, en particulier le Lactobacillus acidophilus, dispersées dans un porteur fluide pharmaceutiquement actif possédant une viscosité d'au moins 2000 cps, de préférence 3000 cps, et en particulier 4000 cps. Le nombre de bactéries par capsule est d'au moins 1 x 106, de préférence au moins 1 x 107. L'activité de dilution (aw) du concentré bactérien et du porteur fluide se situe entre 0,00 et 0,2. Le porteur fluide est de préférence une huile non-hygroscopique contenant un agent d'accroissement de la viscosité comme l'amidon et/ou la vaseline. On a découvert que les capsules résultantes possédaient une activité d'inhibition envers Candida albicans in vitro et in vivo.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK2420/83 | 1983-05-27 | ||
DK2420/83A DK242083D0 (da) | 1983-05-27 | 1983-05-27 | Vaginalkapsler |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0147428A1 true EP0147428A1 (fr) | 1985-07-10 |
Family
ID=8112249
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP84902197A Withdrawn EP0147428A1 (fr) | 1983-05-27 | 1984-05-22 | Capsules vaginales |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0147428A1 (fr) |
JP (1) | JPS60501160A (fr) |
AU (1) | AU3018684A (fr) |
DK (1) | DK242083D0 (fr) |
WO (1) | WO1984004675A1 (fr) |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
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US4670256A (en) * | 1985-09-23 | 1987-06-02 | V. Valhalla Corp. | Vaginal conditioning for sexual activity |
US5804179A (en) * | 1985-12-31 | 1998-09-08 | Research Corporation Technologies, Inc. | Lactobacillus compositions and methods for treating urinary tract infections |
CH674150A5 (fr) * | 1987-10-30 | 1990-05-15 | 2 Oi Mo G Med I Im N I Pirogov | |
IT1227154B (it) * | 1988-08-05 | 1991-03-19 | A Tosi Farmaceutici S R L Nova | Composizioni farmaceutiche per uso ginecologico a base di lattobacilli |
JPH0761949B2 (ja) * | 1990-04-25 | 1995-07-05 | フロイント産業株式会社 | 腸内有用細菌含有組成物 |
DE4123330A1 (de) * | 1991-07-15 | 1993-01-21 | Gerhard Netz | Verfahren zur peranalen keimapplikation |
GB2261372A (en) * | 1991-11-15 | 1993-05-19 | Gregor Reid | Lactobacillus and skim milk compositions for prevention of urogenital infection |
ZA942302B (en) * | 1993-12-03 | 1995-09-29 | Lafor Lab Ltd | Viracidal bactericidal and spermicidal vaginal suppository |
GB2310375A (en) * | 1996-02-21 | 1997-08-27 | Vanessa Clare Mcclafferty | Pessaries for treating vaginal infections |
US6093394A (en) * | 1997-04-11 | 2000-07-25 | Gynelogix, Inc. | Vaginal lactobacillus medicant |
ATE223199T1 (de) * | 1997-04-14 | 2002-09-15 | Tosi A Farma Srl | Pharmazeutische zusammensetzungen mit laktobazillen zur transmucosalen verabreichung |
SE519648C2 (sv) | 1998-03-06 | 2003-03-25 | Essum Ab | Ny stam av Lactobacillus plantarum |
CN1304313A (zh) * | 1998-06-05 | 2001-07-18 | 若素制药株式会社 | 含乳酸菌的组合物、药物和食物 |
DE19922537A1 (de) * | 1999-05-10 | 2000-11-16 | Roland Bodmeier | Darreichungsform zur Applikation in Körperöffnungen |
MXPA03002056A (es) * | 2000-09-12 | 2003-07-24 | Pharmacia & Upjohn Company | Composicion farmaceutica con actividad de agua especifica. |
SE518097C2 (sv) * | 2000-10-03 | 2002-08-27 | Ellen Ab | Förfarande för framställning av en absorberande sanitetsartikel som innefattar mjölksyraproducerande bakterier samt sådant alster |
US7214370B2 (en) | 2000-12-18 | 2007-05-08 | Probiohealth, Llc | Prebiotic and preservative uses of oil-emulsified probiotic encapsulations |
US20040033968A1 (en) * | 2002-08-16 | 2004-02-19 | Lin Shun Y. | Optimal volume of intra-vaginal semisolid dosage forms for treating vaginal infections |
US20040071679A1 (en) * | 2002-10-15 | 2004-04-15 | Claudio De Simone | Identifying and treating vaginal infections |
WO2006045347A1 (fr) * | 2004-10-22 | 2006-05-04 | Medinova Ag | Souche de lactobacillus helveticus utile dans le traitement ou la prevention d'infections engendrees par des pathogenes urogenitaux |
WO2006080035A1 (fr) * | 2004-12-23 | 2006-08-03 | Actial Farmacêutica Lda. | Dispositif et methode d'identification et de traitement des affections vaginales |
WO2007073265A1 (fr) * | 2005-12-22 | 2007-06-28 | Sca Hygiene Products Ab | Article absorbant |
EP1962756B1 (fr) | 2005-12-22 | 2012-10-03 | Sca Hygiene Products Ab | Element support impermeable a la vapeur d'eau destine a etre utilise dans un article absorbant |
US20090036849A1 (en) * | 2005-12-22 | 2009-02-05 | Sca Hygiene Products Ab | Absorbent Article |
ITMI20062286A1 (it) * | 2006-11-28 | 2008-05-29 | Anidral Srl | Una composizione per la somministrazione di principi biologicamente attivi in ambito ginecologico e rettale nonche' i suoi usi |
US20100136210A1 (en) * | 2007-06-21 | 2010-06-03 | Sca Hygiene Products Ab | Sanitary article comprising lactobacilli in a hydrophilic carrier |
EP2173856A1 (fr) * | 2007-06-28 | 2010-04-14 | Chr. Hansen A/S | Traitement de suspension de cellules |
BRPI0812647A2 (pt) * | 2007-07-13 | 2014-09-30 | Unilever Nv | "composição e método para produzir a composição" |
EP2158916A1 (fr) * | 2008-08-27 | 2010-03-03 | Ellen Aktiebolag | Unité d'administration contenant des bactéries produisant de l'acide lactique |
FR2992973B1 (fr) | 2012-07-09 | 2015-12-18 | S P M D | Nouvelle souche de lactobacillus crispatus |
FR2992861B1 (fr) | 2012-07-09 | 2014-10-17 | Probionov | Utilisation de thiosulfate pour potentialiser l'effet anti-pathogene des lactobacilles |
US20140271837A1 (en) * | 2013-03-15 | 2014-09-18 | Warner Chilcott Company, Llc | Pharmaceutical soft gelatin capsule dosage form |
FR3048361B1 (fr) | 2016-03-01 | 2020-12-18 | Biose | Compositions pour le traitement des candidoses |
US20210401879A1 (en) * | 2020-06-30 | 2021-12-30 | Vireo Systems, Inc. | Compositions for controlling odor and itch and methods of and devices for administering same |
WO2022172285A1 (fr) * | 2021-10-18 | 2022-08-18 | Nutra Grace | Capsule vaginale à base d'huile de graines de neem pour le traitement de pertes vaginales anormales |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE605803C (de) * | 1931-06-26 | 1934-11-19 | Iwan Arbatsky | Kapsel fuer Mittel zur Bekaempfung von Faeulnisprozessen im Dickdarm |
DK127268A (fr) * | 1970-01-12 | 1900-01-01 | ||
BG19633A1 (fr) * | 1973-10-11 | 1975-10-10 | ||
DE2738652C3 (de) * | 1977-08-26 | 1981-02-19 | Seiken Kai Foundation Juridical Person, Tondabayashi, Osaka (Japan) | Lactobacillus-Präparat und seine Verwendung bei der Bekämpfung bakterieller Infektionen und Entzündungen |
-
1983
- 1983-05-27 DK DK2420/83A patent/DK242083D0/da not_active Application Discontinuation
-
1984
- 1984-05-22 EP EP84902197A patent/EP0147428A1/fr not_active Withdrawn
- 1984-05-22 WO PCT/DK1984/000042 patent/WO1984004675A1/fr not_active Application Discontinuation
- 1984-05-22 AU AU30186/84A patent/AU3018684A/en not_active Abandoned
- 1984-05-22 JP JP59502258A patent/JPS60501160A/ja active Pending
Non-Patent Citations (1)
Title |
---|
See references of WO8404675A1 * |
Also Published As
Publication number | Publication date |
---|---|
JPS60501160A (ja) | 1985-07-25 |
AU3018684A (en) | 1984-12-18 |
WO1984004675A1 (fr) | 1984-12-06 |
DK242083D0 (da) | 1983-05-27 |
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