US20140147502A1 - Hydrolysates made of plant extracts and antibacterial agent containing the same - Google Patents
Hydrolysates made of plant extracts and antibacterial agent containing the same Download PDFInfo
- Publication number
- US20140147502A1 US20140147502A1 US14/169,250 US201414169250A US2014147502A1 US 20140147502 A1 US20140147502 A1 US 20140147502A1 US 201414169250 A US201414169250 A US 201414169250A US 2014147502 A1 US2014147502 A1 US 2014147502A1
- Authority
- US
- United States
- Prior art keywords
- hydrolysate
- hydrolysate according
- primula
- extract
- ethanol
- 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.)
- Abandoned
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- 239000003242 anti bacterial agent Substances 0.000 title claims abstract description 18
- 239000000419 plant extract Substances 0.000 title claims description 11
- 239000000284 extract Substances 0.000 claims abstract description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 34
- 244000072254 Primula veris Species 0.000 claims abstract description 33
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 32
- 235000002343 Primula veris Nutrition 0.000 claims abstract description 31
- 239000000413 hydrolysate Substances 0.000 claims abstract description 31
- 239000000203 mixture Substances 0.000 claims abstract description 31
- 235000008995 european elder Nutrition 0.000 claims abstract description 28
- 241000196324 Embryophyta Species 0.000 claims abstract description 26
- 240000001519 Verbena officinalis Species 0.000 claims abstract description 26
- 240000006028 Sambucus nigra Species 0.000 claims abstract description 23
- 235000003142 Sambucus nigra Nutrition 0.000 claims abstract description 23
- 235000002873 Gentiana lutea Nutrition 0.000 claims abstract description 22
- 240000003409 Gentiana lutea Species 0.000 claims abstract description 22
- 235000018718 Verbena officinalis Nutrition 0.000 claims abstract description 21
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 19
- 210000002345 respiratory system Anatomy 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000463 material Substances 0.000 claims abstract description 10
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 5
- 210000005069 ears Anatomy 0.000 claims abstract description 5
- 238000000605 extraction Methods 0.000 claims abstract description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 5
- 239000011707 mineral Substances 0.000 claims abstract description 5
- 238000002481 ethanol extraction Methods 0.000 claims abstract description 3
- 238000003809 water extraction Methods 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 25
- 241000606768 Haemophilus influenzae Species 0.000 claims description 18
- 241000894006 Bacteria Species 0.000 claims description 16
- 241000588724 Escherichia coli Species 0.000 claims description 14
- 210000004400 mucous membrane Anatomy 0.000 claims description 12
- 208000015181 infectious disease Diseases 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 8
- 241000191967 Staphylococcus aureus Species 0.000 claims description 7
- 241000191963 Staphylococcus epidermidis Species 0.000 claims description 7
- 241000193998 Streptococcus pneumoniae Species 0.000 claims description 7
- 241000193996 Streptococcus pyogenes Species 0.000 claims description 7
- 239000002775 capsule Substances 0.000 claims description 7
- 229940047650 haemophilus influenzae Drugs 0.000 claims description 7
- 229940031000 streptococcus pneumoniae Drugs 0.000 claims description 7
- 241001071795 Gentiana Species 0.000 claims description 6
- 241000245063 Primula Species 0.000 claims description 5
- 235000000497 Primula Nutrition 0.000 claims description 5
- 238000010790 dilution Methods 0.000 claims description 5
- 239000012895 dilution Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 235000005291 Rumex acetosa Nutrition 0.000 claims description 4
- 240000007001 Rumex acetosella Species 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000012487 rinsing solution Substances 0.000 claims description 4
- 241001522957 Enterococcus casseliflavus Species 0.000 claims description 3
- 241000194032 Enterococcus faecalis Species 0.000 claims description 3
- 241000588747 Klebsiella pneumoniae Species 0.000 claims description 3
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 3
- 244000137827 Rumex acetosa Species 0.000 claims description 3
- 235000015761 Rumex acetosella Nutrition 0.000 claims description 3
- 235000021501 Rumex crispus Nutrition 0.000 claims description 3
- 240000007113 Rumex obtusifolius Species 0.000 claims description 3
- 235000009422 Rumex obtusifolius Nutrition 0.000 claims description 3
- 244000081923 Rumex patientia Species 0.000 claims description 3
- 235000008330 Rumex patientia Nutrition 0.000 claims description 3
- 244000207667 Rumex vesicarius Species 0.000 claims description 3
- 241000194019 Streptococcus mutans Species 0.000 claims description 3
- 229940032049 enterococcus faecalis Drugs 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
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- 238000003756 stirring Methods 0.000 claims description 3
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- 239000003826 tablet Substances 0.000 claims description 3
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- 239000002671 adjuvant Substances 0.000 claims description 2
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- 239000007940 sugar coated tablet Substances 0.000 claims description 2
- 244000052616 bacterial pathogen Species 0.000 abstract description 4
- 210000001331 nose Anatomy 0.000 abstract description 4
- 210000003800 pharynx Anatomy 0.000 abstract description 2
- 210000003491 skin Anatomy 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 18
- 210000003097 mucus Anatomy 0.000 description 12
- 230000001717 pathogenic effect Effects 0.000 description 12
- 241000588748 Klebsiella Species 0.000 description 11
- 230000007062 hydrolysis Effects 0.000 description 10
- 238000006460 hydrolysis reaction Methods 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 8
- 244000052769 pathogen Species 0.000 description 8
- 239000003172 expectorant agent Substances 0.000 description 7
- 230000003419 expectorant effect Effects 0.000 description 7
- 239000009583 Sinupret Substances 0.000 description 6
- 241000208829 Sambucus Species 0.000 description 5
- 210000004081 cilia Anatomy 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- ZKSZEJFBGODIJW-YOVYLDAJSA-N (S)-prunasin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H](C#N)C1=CC=CC=C1 ZKSZEJFBGODIJW-YOVYLDAJSA-N 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- 235000007212 Verbena X moechina Moldenke Nutrition 0.000 description 4
- 235000001594 Verbena polystachya Kunth Nutrition 0.000 description 4
- 235000007200 Verbena x perriana Moldenke Nutrition 0.000 description 4
- 235000002270 Verbena x stuprosa Moldenke Nutrition 0.000 description 4
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- 229930182470 glycoside Natural products 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 201000009890 sinusitis Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 241000738949 Primula halleri Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- -1 cinnamic acid glycosides Chemical class 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000003695 paranasal sinus Anatomy 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
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- 230000001681 protective effect Effects 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- 206010001076 Acute sinusitis Diseases 0.000 description 2
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- 241000588921 Enterobacteriaceae Species 0.000 description 2
- 238000002768 Kirby-Bauer method Methods 0.000 description 2
- 208000018569 Respiratory Tract disease Diseases 0.000 description 2
- 241000219053 Rumex Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 208000027157 chronic rhinosinusitis Diseases 0.000 description 2
- 229930182485 cyanogenic glycoside Natural products 0.000 description 2
- 150000008142 cyanogenic glycosides Chemical class 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 210000002850 nasal mucosa Anatomy 0.000 description 2
- ZKSZEJFBGODIJW-UHFFFAOYSA-N passiedulin Natural products OC1C(O)C(O)C(CO)OC1OC(C#N)C1=CC=CC=C1 ZKSZEJFBGODIJW-UHFFFAOYSA-N 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- QJVHTELASVOWBE-AGNWQMPPSA-N (2s,5r,6r)-6-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21.C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 QJVHTELASVOWBE-AGNWQMPPSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000008749 Caltha palustris Nutrition 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 235000001018 Hibiscus sabdariffa Nutrition 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 235000015924 Primula veris subsp veris Nutrition 0.000 description 1
- 235000016311 Primula vulgaris Nutrition 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010041925 Staphylococcal infections Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- 238000002829 antibacterial sensitivity test Methods 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 229940066493 expectorants Drugs 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 235000011957 flavonols Nutrition 0.000 description 1
- 210000001214 frontal sinus Anatomy 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 235000001545 hohe Schluesselblume Nutrition 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229930182489 iridoid glycoside Natural products 0.000 description 1
- 150000008145 iridoid glycosides Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
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- 239000002075 main ingredient Substances 0.000 description 1
- 210000004086 maxillary sinus Anatomy 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
- CDWVFJJMYKSVHM-HSMQXHTESA-N methyl 5-methoxy-2-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-[[(2s,3r,4s,5r)-3,4,5-trihydroxyoxan-2-yl]oxymethyl]oxan-2-yl]oxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@@H](O)[C@H](O)CO2)O)O1 CDWVFJJMYKSVHM-HSMQXHTESA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 1
- 229960001019 oxacillin Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
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- 235000000683 pigeons grass Nutrition 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
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- 235000003513 sheep sorrel Nutrition 0.000 description 1
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- 239000000725 suspension Substances 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 229930182493 triterpene saponin Natural products 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/51—Gentianaceae (Gentian family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/51—Gentianaceae (Gentian family)
- A61K36/515—Gentiana
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/85—Verbenaceae (Verbena family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention relates to a hydrolysate made of at least one extract from at least one plant material according to the preamble of claim 1 and to an antibacterial agent according to the preamble of claim 18 .
- Extracts from the five indigenous medicinal plants Extracts from the five indigenous medicinal plants:
- Rumicis herba Rumex acetosa L., Rumex acetosella L., Rumex obtusifolius L., Rumex patientia L., and Rumex crispus L.
- Verbena officinalis L. Sambucus nigra L.; Primula veris L. and Primula elatior (L.) Hill
- Gentiana lutea L. together have been known for more than 70 years as secretolytic agents for infections of the upper respiratory tracts, and specifically sinusitis under the brand name of SINUPRET® (registered trademark of BIONORICA).
- Rumicis Herba the active ingredients from the leaves and stems have an expectorant and an anti-inflammatory effect and a positive influence on the body's own defense mechanisms.
- Ingredients include, for example, flavonoids, oxalic acid and different tannins.
- Verbena officinalis (Common Verbena ) has an expectorant and an antiviral effect.
- the main ingredients of the medicinally used leaves and stems include iridoid glycosides, cinnamic acid glycosides, and flavonoids.
- the ingredients include different flavonol glycosides and sambunigrin as the main active ingredient, a cyanogenic glycoside, which has an antiviral effect.
- the ingredients include triterpene saponins and phenol glycosides, such as primulaverin.
- Primula veris and/or Primula elatior act as mild secretolytic agents and expectorants for the treatment of respiratory tract diseases.
- composition which can be used to achieve sufficient effects for medicinal purposes.
- the composition is preferably used for infections of the ear-nose-throat region and is specially suited for treating acute and chronic sinusitis.
- Sinusitis can occur in acute or chronic form. Both forms are frequent, wherein in three out of four cases sinusitis develops as a result of an infection of the mucous membrane from a head cold spreading to the paranasal sinuses.
- the paranasal sinuses are part of the upper respiratory tract.
- the respiratory tract extends from the primary nasal cavity with the different sinuses to the alveoli.
- the paranasal sinuses include the frontal sinuses, the ethmoidal air cells, the sphenoidal sinuses, and the maxillary sinuses. All bony cavities mentioned above are lined on the insides with mucous membranes and open into the primary nasal cavity through narrow openings, referred to as ostia.
- Dirt particles and pathogens such as viruses and bacteria which enter with the respiratory air, adhere to the protective mucous covering the surface of the respiratory tracts and are attacked and rendered harmless by the antibodies present in the mucous.
- the mucous In order to allow foreign bodies to be flushed out of the body, the mucous must be transported with the help of the cilia of the ciliated epithelium in the direction of the pharynx, where it can be swallowed.
- the mucous membrane In order to be able to fend off infection-related respiratory tract diseases, the mucous membrane must have unimpaired protective and cleaning mechanisms at its disposal. For this purpose, it is indispensable, when removing the mucous loaded with pathogenic agents that the cilia can work without impairment and, through the wavy movements thereof, can transport the mucous and that the mucous is fresh and has low viscosity.
- the protective and cleaning mechanisms of the mucous membrane are not longer fully functional.
- Viruses such as rhinoviruses, adenoviruses or coronaviruses trigger inflammatory reactions of the mucous membranes, thereby causing the mucous membrane to swell and produce an increased amount of mucus.
- the result is first a watery, later a viscous mucus flow.
- the ostia of the sinuses can swell shut and mucus can no longer flow into the nose. This creates congestion in the sinuses.
- the cilia can no longer move and stick together.
- the cleaning mechanism of the mucous membrane does not function any more.
- ENT-relevant pathogenic agents settling into the mucus include, for example, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae or Haemophilus influenzae.
- MRSA Staphylococcus aureas strain that is resistant to methicillin
- Standard antibiotics such as ⁇ -lactam antibiotics, for example oxacillin, penicillin and amoxicillin, no longer have an effect on this bacterium, because the excessive use of antibiotics, which do not fully destroy the pathogenic agents, have created resistivity.
- the ground raw drugs and ethanolic/aqueous extracts, or the dry extracts produced therefrom (produced, for example, by withdrawing the solvent/extracting agent at reduced pressure) made of Gentiana lutea, Rumicis herba, Verbena officinalis, Sambucus nigra , and Primula veris are already used in the pharmaceutical product SINUPRET® (as extract: in the formulation as drops; and as coated tablets containing the ground raw drugs) from BIONORICA as a secretolytic agent and has been successfully applied due to the exclusively plant-based healing power.
- BIONORICA achieves the consistent quality of the pharmaceutical product by employing optimally developed cultivation and harvest strategies and extremely stringent quality control.
- the ingredients of the composition used stimulates the formation of fresh, low-viscosity mucus.
- the accumulated mucus can be dissolved and discharged in the direction of the pharyngeal space.
- the inflammation of the nasal mucosa decreases, thereby causing the mucous membrane to go down and the sinuses to open.
- SINUPRET® gently restores the self-cleaning force of the respiratory tract.
- One characteristic of SINUPRET® is the good compatibility thereof, wherein the dosage determined by BIONORICA rarely produces side effects in the patient and no interactions with other pharmaceutical drugs are known.
- the main active ingredient in Sambucus nigra the cyanogenic glycoside sambunigrin, has an antiviral effect, which can be attributed to the fact that it covers the spikes of the flu viruses, by which they can penetrate cells and trigger infections, and blocks them (Grabovac, A. and Ullmer, A., ⁇ tschische maschiner-Verlagsgesellschaft m.b.H., 2003).
- German patent specification DE 10 2005 053 926 B3 describes a topical antibacterial effect of the above-mentioned individual drugs and the drug mixture.
- the invention relates in particular to a hydrolysate made of at least one extract, which is produced by extraction using ethanol/water from dried plant material:
- a) at least one of the plants selected from the group consisting of: Verbena officinalis L., Sambucus nigra L., Primula veris L., Primula elatior (L.) Hill and Gentiana lutea L.; and a mixture thereof; or b) a mixture of: Verbena officinalis L., Sambucus nigra L., Primula veris L., Gentiana lutea L. and Rumicis herba ; and subsequent removal of the ethanol/water extraction agent, wherein the hydrolysate can be obtained from the extract by way of hydrolytic treatment using a mineral acid.
- a preferred hydrolysate is characterized in that the extracts can be produced from the plant material using an extraction agent made of 50% by volume ethanol and 50% by volume water over 24 hours while stirring and subsequent vacuum evaporation of the solvent.
- a further preferred embodiment of the invention is a hydrolysate which can be obtained by the hydrolytic treatment of the plant extracts with hydrochloric acid as the mineral acid, in particular hydrochloric acid having a concentration of 1 M to 10 M, preferably 6 to 9 M, in particular approximately 8 M, at 80° C. to 100° C., particularly approximately 90° C., for 30 minutes to 120 minutes, in particular 40 minutes to 60 minutes, preferably approximately 45 minutes.
- hydrochloric acid as the mineral acid
- hydrochloric acid having a concentration of 1 M to 10 M, preferably 6 to 9 M, in particular approximately 8 M, at 80° C. to 100° C., particularly approximately 90° C., for 30 minutes to 120 minutes, in particular 40 minutes to 60 minutes, preferably approximately 45 minutes.
- ethanol in particular ethanol diluted with water, preferably 50% by volume ethanol.
- the extracts are evaporated to dryness after the acid treatment step, placed preferably in water, a buffer, or in diluted ethanol, and optionally neutralized with a pharmaceutically acceptable alkali.
- a pharmaceutically acceptable alkali Possible alkalis are, for example, NaOH, Na 2 CO 3 or Na 2 HPO 4 .
- the hydrolysate is preferably produced from an extract stemming from the following plant components:
- Rumicis herba Rumex acetosa L., Rumex acetosella L., Rumex obtusifolius L., Rumex patientia L. and Rumex crispus I.
- Leaves and stems Verbena officinalis : leaves and upper stem sections
- Sambucus nigra blossoms Primula veris and/or Primula eliator : blossoms and capsules
- Gentiana lutea roots.
- hydrolysate made of an extract of a mixture of:
- Gentiana lutea roots; Rumicis herba : leaves and stems; Verbena officinalis : leaves and upper stem sections; Sambucus nigra : blossoms; and Primula veris : blossoms and capsules; wherein the individual drugs are present in the extract to be hydrolyzed in particular in a mass ratio of 1:1:1:1:1 to 1:3:3:3:3.
- the hydrolysates of the present invention generally have a significant antibacterial effect, which in the scope thereof is comparable to an antibiotic control agent made of amoxicillin and clavulanic acid (mass ratio of 6:1). In contrast, non-hydrolytically treated pure extract exhibit only a low to no antibacterial activity in the test system used.
- the hydrolysates of the present invention can be used to produce agents having an antibacterial effect against skin and respiratory tract relevant bacteria, in particular gram positive cocci, especially Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus mutans and/or gram negative rod bacteria, in particular Haemophilus influenzae.
- gram positive cocci especially Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus mutans and/or gram negative rod bacteria, in particular Haemophilus influenzae.
- the hydrolysates were tested within the context of the present invention against the following skin, ENT and respiratory tract relevant pathogenic agents and found to be effective: Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Streptococcus pneumoniae (DSMZ 20566), Streptococcus pyogenes (DSMZ 20565), Streptococcus mutans (ATCC 35668), Haemophilus influenzae (DSMZ 4690), Klebsiella pneumoniae (ATCC 13883), and Enterococcus casseliflavus (VRE) (DSMZ 20680) as well as, against intestinal bacteria, Escherichia coli (ATCC 25922) and Enterococcus faecalis (VRE) (ATCC 19433).
- Staphylococcus aureus ATCC 25923
- Staphylococcus epidermidis ATCC 12228
- the hydrolysates of the present invention can advantageously and in manners which are known for producing an antibacterial agent.
- antibacterial agents can be used for the protection against and/or treatment of infections, or topically on the skin and mucous membranes in the form of a galenic formulation that corresponds to the applications thereof.
- the galenic formulations of the hydrolysates/antibacterial agents of the present invention are characterized in that the oral formulations comprises sugar-coated tablets, tablets, film-coated tablets, powders, capsules, or liquid dilutions, in particular drops, oral solutions or syrups.
- the tamponades mentioned above are also suited for dental applications.
- hydrolysates according to the invention are advantageously used in combination with physiological or hyperosmolar concentrations of salts or salt mixtures.
- a preparation present as a lyophilisate has many advantages, these being in particular storage and long-term stability.
- the antibacterial agents of the present invention can, of course, contain the pharmaceutically customary adjuvants.
- hydrolysates according to the invention have a broad, in part pronounced antibacterial effect against skin, respiratory tract and ENT-relevant pathogenic agents, which in corresponding tests with respect to the antibacterial effect were considerably more pronounced than was the case of non-hydrolyzed extracts.
- antibacterial sensitivity tests using the agar diffusion test according to Mueller-Hinton [Mueller, H. J. and Hinton, J. (1941): A protein-free medium for primary isolation of the Gonococcus and Meningococcus. Proc. Soc. Expt. Biol.
- the hydrolysates and the antibacterial agent of the present invention can therefore advantageously be used for the treatment of infections triggered by respiratory tract-relevant pathogenic agents.
- the expectorant and anti-inflammatory effects of the analyzed drugs and drug mixtures were supplemented by the additional antibacterial effect, whereby an infection of the upper respiratory tracts is not only reduced by dissolving the viscous, pathogen-loaded mucus, but is completely eliminated by destroying the bacterial pathogenic agents.
- the antibacterial agent of the present invention is effective in particular against the following pathogenic agents, exhibiting antibacterial efficacy in particular against gram positive cocci such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae , and against gram negative rod-shaped bacteria such as Klebsiella, Haemophilus influenzae, Pseudomonas aeruginosa as well as against Enterobacteriaceae faecalis (VRE), Enterobacteriaceae casseliflavus and E. coli.
- pathogenic agents exhibiting antibacterial efficacy in particular against gram positive cocci such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae
- gram negative rod-shaped bacteria such as Klebsiella, Haemophilus influenzae, Pseudomon
- the present invention also relates to the use of the hydrolysates and antibacterial agents according to the invention for producing a pharmaceutical product for the treatment of infections of the respiratory tract and ENT space triggered by respiratory tract and ENT-relevant pathogenic agents.
- EtOH/H 2 O v/v, approx. 1 g plant material for 20 ml solvent
- the mass ratio of the individual drugs was 1:1:1:1:1, 1:1:1:1, 1:1:1.
- Non-hydrolyzed extracts were present in 50% EtOH/H 2 O (see above), wherein optionally by evaporation the concentrations of the ingredients of the non-hydrolyzed and hydrolyzed extracts were aligned with each other. As a result, the extracted ingredients were present in the same volumes when the same masses of plant drugs were used.
- test solution 80 ⁇ l of the test solution (non-hydrolyzed or hydrolyzed) was placed on Muller Hinton agar plates or Muller Hinton Agar plates with 5% sheep blood containing an unknown concentration of the bacteria to be tested and incubated for 24 hours at 37° C.
- Spiral platter 80 ⁇ l of the test solution (non-hydrolyzed or hydrolyzed) was placed on Muller Hinton agar plates or Muller Hinton Agar plates with 5% sheep blood containing an unknown concentration of the bacteria to be tested and incubated for 24 hours at 37° C.
- a bacteria colony was suspended in 5 ml CASO-Bouillon and incubated for 24 hours at 37° C.
- the supernatant was removed after centrifuging the sample, washed with 0.9% NaCl, and diluted to a concentration of 10 7 cfu/ml (colony forming unit per milliliter).
- test solution non-hydrolyzed or hydrolyzed
- bacteria suspension for Pneumococcus and H. influenzae: 1:10, for the remaining pathogens 1:100. 0.9% NaCl was used for positive control purposes.
- the samples are plated with a Whitley Automatic Spiral Platter (WASP) after 0.4 and 8 hours and incubated for 24 hours at 37° C.
- WASP Whitley Automatic Spiral Platter
- aeruginosa (ATCC 27853), Streptococcus pneumoniae ( Pneumococcus ) (DSMZ 20566), Streptococcus pyogenes ( Strept. pyogenes )(DSMZ 20565), Klebsiella pneumoniae ( Klebsiella ) (ATCC 13883), Escherichia coli ( E. coli ) (A TCC 25922), Haemophilus influenzae ( H. influenzae ) (DSMZ 4690), Staphylococcus epidermidis ( Staph. epidermidis ) (ATCC 12228), Enterococcus faecalis (VRE) ( Ent.
- VRE Enterococcus casseliflavus
- VRE Ent. casseliflavus
- DSMZ 20680 5-plant Gentiana l. Sambucus n. Verbena o. Rumicis h. Primula v. extract Staph. aureus ⁇ ⁇ ⁇ + +M ⁇ P. aeruginosa ⁇ +B ⁇ +B ⁇ ⁇ Pneumococcus ⁇ ⁇ ⁇ +M +M ⁇ Strept. pyogenes ⁇ ⁇ ⁇ +M +M ⁇ Klebsiella ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ E.
- VRE epidermidis ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ Ent. faecalis (VRE) ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ Ent. casseliflavus ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ (VRE) RGP RGS RGV RVS GSP Staph. aureus + ⁇ ⁇ ⁇ ⁇ P. aeruginosa ⁇ ⁇ ⁇ ⁇ ⁇ Pneumococcus ⁇ ⁇ ⁇ ⁇ Strept. pyogenes ⁇ + ⁇ ⁇ ⁇ Klebsiella ⁇ ⁇ ⁇ ⁇ ⁇ E.
- VRE faecalis
- VRE faecalis
- VRE ++ (+) ++ Ent. casseliflavus
- VRE ++ ++ +++ Gentiana l .
- VRE casseliflavus
- VRE casseliflavus +++ +++ ++++++ Ex- Ex- Ex- Ex- Primula v . tract 1 tract 2 tract 3 tract 4 tract 5 Staph. aureus +++ (+) ++ (+) + P. aeruginosa ++++ +++ ++++ ++++++ ++++++++++++++++++++++++++ Pneumococcus ++++ (+) +++ +++ +++ +++ Strept. pyogenes ++++ +++ ++++++++ +++ Klebsiella +++ (+) ++++ + +++ E. coli + (+) +++ ++ + H. influenzae ++++ +++ ++++++++ ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Abstract
The present invention relates to an antibacterial agent and a hydrolysate made of at least one extract that has been produced by extraction using ethanol/water from dried plant material of: a) at least one of the plants selected from the group consisting of: Verbena officinalis L., Sambucus nigra L., Primula veris L., Primula elatior (L.) Hill, and Gentiana lutea L.; and a mixture thereof; or b) a mixture of: Verbena officinalis L., Sambucus nigra L., Primula veris L., Gentiana lutea L., and Rumicis herba; and subsequent removal of the ethanol/water extraction agent, wherein the hydrolysate can be obtained from the extract via hydrolytic treatment using a mineral acid. The hydrolyzates according to the invention show a pronounced antibacterial effect against germs relevant to the skin, ears, nose, and throat and respiratory systems.
Description
- This patent application is a continuation of application Ser. No. 12/740,396, filed on Sep. 10, 2010, the entire contents of which is incorporated by reference herein in its entirety. Application Ser. No. 12/740,396 is a national stage application under 35 U.S.C. §371 of PCT/EP08/09171, filed on Oct. 30, 2008, which claims priority of German patent application 10 2007 052 223.3, filed Oct. 31, 2007, which is incorporated by reference herein in its entirety.
- The present invention relates to a hydrolysate made of at least one extract from at least one plant material according to the preamble of claim 1 and to an antibacterial agent according to the preamble of claim 18.
- Extracts from the five indigenous medicinal plants:
- Rumicis herba (Rumex acetosa L., Rumex acetosella L., Rumex obtusifolius L., Rumex patientia L., and Rumex crispus L.);
Verbena officinalis L.;
Sambucus nigra L.;
Primula veris L. and Primula elatior (L.) Hill; and
Gentiana lutea L.
together have been known for more than 70 years as secretolytic agents for infections of the upper respiratory tracts, and specifically sinusitis under the brand name of SINUPRET® (registered trademark of BIONORICA). - Each individual drug contributes a part to the unique efficacy of the composition:
- From Gentiana lutea (Yellow Gentian), typically the root is used for medicinal purposes. The ingredients which have an expectorant effect also include several secoiridoid glycosides.
- In Rumicis Herba (sorrel herb), the active ingredients from the leaves and stems have an expectorant and an anti-inflammatory effect and a positive influence on the body's own defense mechanisms. Ingredients include, for example, flavonoids, oxalic acid and different tannins.
- Verbena officinalis (Common Verbena) has an expectorant and an antiviral effect. The main ingredients of the medicinally used leaves and stems include iridoid glycosides, cinnamic acid glycosides, and flavonoids.
- From Sambucus nigra (Black Elder), the blossoms are used and the ingredients thereof have an expectorant effect. The ingredients include different flavonol glycosides and sambunigrin as the main active ingredient, a cyanogenic glycoside, which has an antiviral effect.
- The active ingredients from the blossoms and capsules of Primula veris (Cowslip) and/or Primula elatior (L.) Hill (True oxlip) fight viruses and have an expectorant effect. The ingredients include triterpene saponins and phenol glycosides, such as primulaverin. Primula veris and/or Primula elatior act as mild secretolytic agents and expectorants for the treatment of respiratory tract diseases.
- By combining these five medicinal plants, a composition is obtained, which can be used to achieve sufficient effects for medicinal purposes. The composition is preferably used for infections of the ear-nose-throat region and is specially suited for treating acute and chronic sinusitis.
- Sinusitis can occur in acute or chronic form. Both forms are frequent, wherein in three out of four cases sinusitis develops as a result of an infection of the mucous membrane from a head cold spreading to the paranasal sinuses.
- The paranasal sinuses are part of the upper respiratory tract. The respiratory tract extends from the primary nasal cavity with the different sinuses to the alveoli. The paranasal sinuses include the frontal sinuses, the ethmoidal air cells, the sphenoidal sinuses, and the maxillary sinuses. All bony cavities mentioned above are lined on the insides with mucous membranes and open into the primary nasal cavity through narrow openings, referred to as ostia.
- Dirt particles and pathogens, such as viruses and bacteria which enter with the respiratory air, adhere to the protective mucous covering the surface of the respiratory tracts and are attacked and rendered harmless by the antibodies present in the mucous. In order to allow foreign bodies to be flushed out of the body, the mucous must be transported with the help of the cilia of the ciliated epithelium in the direction of the pharynx, where it can be swallowed.
- In order to be able to fend off infection-related respiratory tract diseases, the mucous membrane must have unimpaired protective and cleaning mechanisms at its disposal. For this purpose, it is indispensable, when removing the mucous loaded with pathogenic agents that the cilia can work without impairment and, through the wavy movements thereof, can transport the mucous and that the mucous is fresh and has low viscosity.
- During an infection, the protective and cleaning mechanisms of the mucous membrane are not longer fully functional.
- Viruses such as rhinoviruses, adenoviruses or coronaviruses trigger inflammatory reactions of the mucous membranes, thereby causing the mucous membrane to swell and produce an increased amount of mucus. The result is first a watery, later a viscous mucus flow. During the course of the inflammation of the nasal mucosa, the ostia of the sinuses can swell shut and mucus can no longer flow into the nose. This creates congestion in the sinuses. In the viscous mucus, the cilia can no longer move and stick together. The cleaning mechanism of the mucous membrane does not function any more.
- In such an environment marked by viscous mucus, the ubiquitously present bacteria fell particularly well. The mucus constitutes an optimal culture medium for bacteria, where they can rapidly multiply. In this way, acute sinusitis is the result of an initially simple cold in three out of four cases.
- If these unfavorable conditions, such as a swollen mucous membrane and sticky cilia due to viscous mucus, last for a longer period, the result can be chronic sinusitis, which can permanently damage the mucous membrane and cilia.
- ENT-relevant pathogenic agents settling into the mucus include, for example, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae or Haemophilus influenzae.
- Among them is also a Staphylococcus aureas strain that is resistant to methicillin, called MRSA. Standard antibiotics such as β-lactam antibiotics, for example oxacillin, penicillin and amoxicillin, no longer have an effect on this bacterium, because the excessive use of antibiotics, which do not fully destroy the pathogenic agents, have created resistivity. These germs represent an additional risk in surgical intensive care units, where they can cause pneumonia, wound infections, and blood poisoning.
- The ground raw drugs and ethanolic/aqueous extracts, or the dry extracts produced therefrom (produced, for example, by withdrawing the solvent/extracting agent at reduced pressure) made of Gentiana lutea, Rumicis herba, Verbena officinalis, Sambucus nigra, and Primula veris are already used in the pharmaceutical product SINUPRET® (as extract: in the formulation as drops; and as coated tablets containing the ground raw drugs) from BIONORICA as a secretolytic agent and has been successfully applied due to the exclusively plant-based healing power.
- The medicinal plants used in SINUPRET® are carefully selected, analyzed, and processes. BIONORICA achieves the consistent quality of the pharmaceutical product by employing optimally developed cultivation and harvest strategies and extremely stringent quality control.
- In the event of an obstruction of the upper respiratory tract by viscous mucus, the ingredients of the composition used (Gentiana lutea:Rumicis herba:Verbena officinalis:Sambucus nigra:Primula veris=1:3:3:3:3) stimulates the formation of fresh, low-viscosity mucus. In this way, the accumulated mucus can be dissolved and discharged in the direction of the pharyngeal space. The inflammation of the nasal mucosa decreases, thereby causing the mucous membrane to go down and the sinuses to open. In this way, SINUPRET® gently restores the self-cleaning force of the respiratory tract. One characteristic of SINUPRET® is the good compatibility thereof, wherein the dosage determined by BIONORICA rarely produces side effects in the patient and no interactions with other pharmaceutical drugs are known.
- The main active ingredient in Sambucus nigra, the cyanogenic glycoside sambunigrin, has an antiviral effect, which can be attributed to the fact that it covers the spikes of the flu viruses, by which they can penetrate cells and trigger infections, and blocks them (Grabovac, A. and Ullmer, A., Österreichische Apotheker-Verlagsgesellschaft m.b.H., 2003).
- The German patent specification DE 10 2005 053 926 B3 describes a topical antibacterial effect of the above-mentioned individual drugs and the drug mixture.
- This effect was surprising to the professional world, because it was believed until then that extracts from Rumicis herba, Verbena officinalis, Sambucus nigra, and Primula veris exhibit only secretolytic, but not antibacterial effects.
- In addition, it is known from the German patent application DE 103 41 579 A1 relating to Gentiana lutea extracts that they exhibit an antibacterial effect.
- While in both cases, there is a clinically highly interesting spectrum of efficacy against a plurality of clinically relevant germs, the necessary dosages are at times not very practical.
- Proceeding from the prior art disclosed in DE 10 2005 053 926 B43 of the SINUPRET® composition, it is therefore the object of the present invention to provide a material which exhibits improved antibacterial efficacy.
- The above object is achieved by the characterizing features of claims 1 and 18.
- The invention relates in particular to a hydrolysate made of at least one extract, which is produced by extraction using ethanol/water from dried plant material:
- a) at least one of the plants, selected from the group consisting of: Verbena officinalis L., Sambucus nigra L., Primula veris L., Primula elatior (L.) Hill and Gentiana lutea L.; and a mixture thereof; or
b) a mixture of: Verbena officinalis L., Sambucus nigra L., Primula veris L.,
Gentiana lutea L. and Rumicis herba; and
subsequent removal of the ethanol/water extraction agent, wherein the hydrolysate can be obtained from the extract by way of hydrolytic treatment using a mineral acid. - A preferred hydrolysate is characterized in that the extracts can be produced from the plant material using an extraction agent made of 50% by volume ethanol and 50% by volume water over 24 hours while stirring and subsequent vacuum evaporation of the solvent.
- A further preferred embodiment of the invention is a hydrolysate which can be obtained by the hydrolytic treatment of the plant extracts with hydrochloric acid as the mineral acid, in particular hydrochloric acid having a concentration of 1 M to 10 M, preferably 6 to 9 M, in particular approximately 8 M, at 80° C. to 100° C., particularly approximately 90° C., for 30 minutes to 120 minutes, in particular 40 minutes to 60 minutes, preferably approximately 45 minutes.
- It is preferred to carry out the hydrolytic treatment of the extracts in the presence of ethanol, in particular ethanol diluted with water, preferably 50% by volume ethanol.
- In order to ensure that the hydrolysates of the present invention have good physiological compatibility, the extracts are evaporated to dryness after the acid treatment step, placed preferably in water, a buffer, or in diluted ethanol, and optionally neutralized with a pharmaceutically acceptable alkali. Possible alkalis are, for example, NaOH, Na2CO3 or Na2HPO4.
- The hydrolysate is preferably produced from an extract stemming from the following plant components:
- Rumicis herba (Rumex acetosa L., Rumex acetosella L., Rumex obtusifolius L., Rumex patientia L. and Rumex crispus I.): leaves and stems
Verbena officinalis: leaves and upper stem sections
Sambucus nigra: blossoms
Primula veris and/or Primula eliator: blossoms and capsules
Gentiana lutea: roots. - Particularly preferred is a hydrolysate made of an extract of a mixture of:
- Gentiana lutea: roots;
Rumicis herba: leaves and stems;
Verbena officinalis: leaves and upper stem sections;
Sambucus nigra: blossoms; and
Primula veris: blossoms and capsules;
wherein the individual drugs are present in the extract to be hydrolyzed in particular in a mass ratio of 1:1:1:1:1 to 1:3:3:3:3. - It came as a complete surprise when it was found that the hydrolysates according to the invention exhibit an antibacterial effect.
- The hydrolysates of the present invention generally have a significant antibacterial effect, which in the scope thereof is comparable to an antibiotic control agent made of amoxicillin and clavulanic acid (mass ratio of 6:1). In contrast, non-hydrolytically treated pure extract exhibit only a low to no antibacterial activity in the test system used.
- The hydrolysates of the present invention can be used to produce agents having an antibacterial effect against skin and respiratory tract relevant bacteria, in particular gram positive cocci, especially Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus mutans and/or gram negative rod bacteria, in particular Haemophilus influenzae.
- The hydrolysates were tested within the context of the present invention against the following skin, ENT and respiratory tract relevant pathogenic agents and found to be effective: Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Streptococcus pneumoniae (DSMZ 20566), Streptococcus pyogenes (DSMZ 20565), Streptococcus mutans (ATCC 35668), Haemophilus influenzae (DSMZ 4690), Klebsiella pneumoniae (ATCC 13883), and Enterococcus casseliflavus (VRE) (DSMZ 20680) as well as, against intestinal bacteria, Escherichia coli (ATCC 25922) and Enterococcus faecalis (VRE) (ATCC 19433).
- The hydrolysates of the present invention can advantageously and in manners which are known for producing an antibacterial agent. Such antibacterial agents can be used for the protection against and/or treatment of infections, or topically on the skin and mucous membranes in the form of a galenic formulation that corresponds to the applications thereof.
- The galenic formulations of the hydrolysates/antibacterial agents of the present invention are characterized in that the oral formulations comprises sugar-coated tablets, tablets, film-coated tablets, powders, capsules, or liquid dilutions, in particular drops, oral solutions or syrups.
- When used for topical applications, in particular sprays, ointments, emulsions, powders, liquid or solid preparations for inhalation, compresses, wound and gum dressings, tamponades, tonsil brush solutions, gargling solutions, or rinsing solutions for the nose and ears are suited.
- The tamponades mentioned above are also suited for dental applications.
- In order to use the hydrolysates according to the invention as rinsing solutions for the nose and ears, they are advantageously used in combination with physiological or hyperosmolar concentrations of salts or salt mixtures.
- For the use as an antibacterial agent, it has been found that a preparation present as a lyophilisate has many advantages, these being in particular storage and long-term stability.
- The antibacterial agents of the present invention can, of course, contain the pharmaceutically customary adjuvants.
- During microbiological analyses conducted at the Institute for Analytical Chemistry and Radiochemistry at the University of Innsbruck, it was surprisingly found that the hydrolysates according to the invention have a broad, in part pronounced antibacterial effect against skin, respiratory tract and ENT-relevant pathogenic agents, which in corresponding tests with respect to the antibacterial effect were considerably more pronounced than was the case of non-hydrolyzed extracts. For example, antibacterial sensitivity tests using the agar diffusion test according to Mueller-Hinton [Mueller, H. J. and Hinton, J. (1941): A protein-free medium for primary isolation of the Gonococcus and Meningococcus. Proc. Soc. Expt. Biol. Med.; 48:330-333] showed that out of the five non-hydrolyzed individual drug extracts only Rumicis herba and Primula veris were effective against multiple pathogenic agents, and that the non-hydrolyzed mixture of Gentiana lutea, Sambucus nigra, Verbena officinalis, Rumicis herba, and Primula veris surprisingly showed practically no antibacterial effect against the bacteria reference panel tested in the agar diffusion test. Interestingly, the same findings, that is, that the antibacterial effect is aimed at one germ at most, was also found for the different combinations of at least three individual drugs among the five that are mentioned.
- This is analogous to the German patent specification DE 10 2005 053 926 B3, which indicates that the antibacterial effect of non-hydrolyzed individual drugs or combinations thereof can likewise only be observed for just a few germs. With respect to the pathogenic agents which exhibited an effect for the non-hydrolyzed extracts and the extent of the effect there is broad agreement between the prior art and the present invention.
- Initially, the finding that, after hydrolysis of the extracts of the individual drugs, the antibacterial effects thereof were in part reversed was all the more surprising: For example, a hydrolyzed extract according to the invention made of Rumicis herba practically exhibited no antibacterial activity any more, while the non-hydrolyzed extract had previously exhibited the most pronounced effect against most of the bacterial strains that were tested.
- The biggest surprise, however, was that a hydrolysate made of a mixture of Gentiana lutea, Sambucus nigra, Verbena officinalis, Primula veris, and Rumicis herba exhibits a significant antibacterial effect against all bacterial strains that were tested.
- The hydrolysates and the antibacterial agent of the present invention can therefore advantageously be used for the treatment of infections triggered by respiratory tract-relevant pathogenic agents. The expectorant and anti-inflammatory effects of the analyzed drugs and drug mixtures were supplemented by the additional antibacterial effect, whereby an infection of the upper respiratory tracts is not only reduced by dissolving the viscous, pathogen-loaded mucus, but is completely eliminated by destroying the bacterial pathogenic agents.
- Due to the medicinal effect on the basis of the five medicinal plants, that is Gentiana lutea, Rumicis herba, Verbena officinalis, Sambucus nigra, and Primula veris, a patient suffering from sinusitis will receive gentle treatment without synthetic-chemical components. In addition, the preparation is marked by good compatibility with respect to the interactions thereof with other drugs and with respect to side effects, which rarely occur.
- The antibacterial agent of the present invention is effective in particular against the following pathogenic agents, exhibiting antibacterial efficacy in particular against gram positive cocci such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, and against gram negative rod-shaped bacteria such as Klebsiella, Haemophilus influenzae, Pseudomonas aeruginosa as well as against Enterobacteriaceae faecalis (VRE), Enterobacteriaceae casseliflavus and E. coli.
- As a result, the present invention also relates to the use of the hydrolysates and antibacterial agents according to the invention for producing a pharmaceutical product for the treatment of infections of the respiratory tract and ENT space triggered by respiratory tract and ENT-relevant pathogenic agents.
- Additional advantages and characteristics of the present invention will be apparent from the description of the exemplary embodiments.
- The individual drugs Gentiana lutea, Rumicis herba, Verbena officinalis, Sambucus nigra, and Primula veris as well as mixed extracts thereof having variable drug compositions (5-plant extract, 4-plant extract, 3-plant extract) were extracted in 50% EtOH/H2O (v/v, approx. 1 g plant material for 20 ml solvent) for 24 hours at room temperature while stirring. For the mixed extracts, this means that from each plant, as stated above, approximately 1 g of material was used, wherein such a material mixture was extracted with a total of 20 ml of solvent. The mass ratio of the individual drugs was 1:1:1:1:1, 1:1:1:1, 1:1:1.
- 1.6 ml of the above-described extracts was mixed with 320 μl of 25% HCl (corresponds to 8.1 mol/L) and 80 μl 50% EtOH and hydrolyzed for 45 minutes at 90° C.
- For comparison purposes, in a second step, the hydrolysis was conducted with 1 ml extract under the same conditions, while adding 1 ml 25% HCl.
- After concentrating the extracts by evaporation, the residue was placed in 1 ml sterile water, and the test solution obtained in this way was tested for the antibacterial effect thereof.
- The effects of the hydrolysates were compared to the effects of the individual or mixed extracts prior to hydrolysis. Non-hydrolyzed extracts were present in 50% EtOH/H2O (see above), wherein optionally by evaporation the concentrations of the ingredients of the non-hydrolyzed and hydrolyzed extracts were aligned with each other. As a result, the extracted ingredients were present in the same volumes when the same masses of plant drugs were used.
- Analysis of the Antibacterial Effect Before and after Hydrolysis of the Plant Extracts Screening Method:
- 80 μl of the test solution (non-hydrolyzed or hydrolyzed) was placed on Muller Hinton agar plates or Muller Hinton Agar plates with 5% sheep blood containing an unknown concentration of the bacteria to be tested and incubated for 24 hours at 37° C. Spiral platter:
- A bacteria colony was suspended in 5 ml CASO-Bouillon and incubated for 24 hours at 37° C.
- The supernatant was removed after centrifuging the sample, washed with 0.9% NaCl, and diluted to a concentration of 107 cfu/ml (colony forming unit per milliliter).
- Also 80 μl test solution (non-hydrolyzed or hydrolyzed) was diluted 1:2, 1:20 and 1:200 and mixed with the bacteria suspension (for Pneumococcus and H. influenzae: 1:10, for the remaining pathogens 1:100). 0.9% NaCl was used for positive control purposes.
- The samples are plated with a Whitley Automatic Spiral Platter (WASP) after 0.4 and 8 hours and incubated for 24 hours at 37° C.
-
-
TABLE 1 Results of the analysis for antibacterial effects of the individual extracts Gentiana lutea (Gentiana l.), Sambucus nigra (Sambucus n.), Verbena officinalis (Verbena o.), Rumex herba (Rumex h.) and Primula veris (Primula v.) as well as a mixed extract made of all 5 plants (5 plant extract) against the pathogens Staphylococcus aureus (Staph. aureus) (A TCC 25923), Pseudomonas aeruginosa (P. aeruginosa) (ATCC 27853), Streptococcus pneumoniae (Pneumococcus) (DSMZ 20566), Streptococcus pyogenes (Strept. pyogenes)(DSMZ 20565), Klebsiella pneumoniae (Klebsiella) (ATCC 13883), Escherichia coli (E. coli) (A TCC 25922), Haemophilus influenzae (H. influenzae) (DSMZ 4690), Staphylococcus epidermidis (Staph. epidermidis) (ATCC 12228), Enterococcus faecalis (VRE) (Ent. faecalis (VRE) (ATCC 19433) and Enterococcus casseliflavus (VRE) (Ent. casseliflavus (VRE) (DSMZ 20680). 5-plant Gentiana l. Sambucus n. Verbena o. Rumicis h. Primula v. extract Staph. aureus Ø Ø Ø + +M Ø P. aeruginosa Ø +B Ø +B Ø Ø Pneumococcus Ø Ø Ø +M +M Ø Strept. pyogenes Ø Ø Ø +M +M Ø Klebsiella Ø Ø Ø Ø Ø Ø E. coli Ø Ø Ø Ø Ø Ø H. influenzae Ø Ø Ø Ø Ø Ø Staph. epidermidis Ø Ø Ø + Ø Ø Ent. faecalis (VRE) Ø Ø Ø + Ø Ø Ent. casseliflavus Ø Ø Ø +M Ø Ø (VRE) +M = antibacterial effect on Mueller Hinton Agar; +B = antibacterial effect on Mueller Hinton Agar with 5% sheep blood; + = effect on both plates.
Spiral Platter: Rumicis herba, Before Hydrolysis -
TABLE 2 Quantification of the antibacterial effect of Rumicis herba and Primula veris against the pathogens mentioned in Table 1 using spiral plating. The samples were quantified in 1:20 or 1:200 dilutions. Rumicis h. Primula v. 1:20 1-200 1:20 1-200 Staph. aureus +++ + ++ (+) P. aeruginosa Ø Ø Ø Ø Pneumococcus ++++ ++++ ++++ ++++ Strept. pyogenes ++++ ++++ ++++ ++ Klebsiella Ø Ø Ø Ø E. coli Ø Ø Ø Ø H. influenzae Ø Ø Ø Ø Staph. epidermidis ++ ++ Ø Ø Ent. faecalis (VRE) ++++ ++++ Ø Ø Ent. casseliflavus ++++ ++++ Ø Ø ++++ = 102 cfu/ml after 0 h, +++ = 102 cfu/ml after 4 h, ++ = 102 cfu/ml after 8 h, + = 103-104 cfu/ml after 8 hours, (+) = higher activity compared to control group -
-
TABLE 3 From the individual drugs mentioned in Table 1, 50% ethanolic mixed extracts comprising 5, 4, or 3 plants were produced and analyzed for the antibacterial effects thereof against the pathogens mentioned in Table 1 in screening tests. Gentiana lutea (G), Sambucus nigra (S), Verbena officinalis (V), Rumicis herba (R), and Primula veris (P). RGVS RVSP RGVP RGSP RGVS GVSP RVP VSP GVP GVSP RS Staph. aureus Ø + + + (+) (+) Ø Ø Ø Ø (+) P. aeruginosa Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Pneumococcus Ø Ø Ø Ø Ø Ø (+) Ø Ø Ø Ø Strept. pyogenes Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø + Klebsiella Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø E. coli Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø H. influenzae Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Staph. epidermidis Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ent. faecalis (VRE) Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ent. casseliflavus Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø Ø (VRE) RGP RGS RGV RVS GSP Staph. aureus + Ø Ø Ø Ø P. aeruginosa Ø Ø Ø Ø Ø Pneumococcus Ø Ø Ø Ø Ø Strept. pyogenes Ø + Ø Ø Ø Klebsiella Ø Ø Ø Ø Ø E. coli Ø Ø Ø Ø Ø H. influenzae Ø Ø Ø Ø Ø Staph. epidermidis Ø Ø Ø Ø Ø Ent. faecalis (VRE Ø Ø Ø Ø Ø Ent. casseliflavus Ø Ø Ø Ø Ø (VRE) + = effect on both plates (Müller Hinton Agar, MOiler Hinton Agar with 5% sheep blood), (+) = effect on one plate - Screening Tests: Individual Drugs/Mixed Extracts after Hydrolysis
-
TABLE 4 The extracts obtained of the plant drugs mentioned in Table 1 as well as a mixed extract comprising all five plants was hydrolyzed using hydrochloric acid and tested for the antibacterial effect against the pathogens listed in Table 1. After the hydrolysis was conducted, the extracts were evaporated to dryness and dissolved in sterile water. 5 plant Gentiana l. Sambucus n. Verbena o. Rumicis h. Primula v. extract Staph. aureus + + Ø Ø + + P. aeruginosa + (+) Ø Ø + + Pneumococcus + + + Ø + + Strept. pyogenes + + + Ø + + Klebsiella + (+) Ø Ø + + E. coli + Ø Ø Ø + + H. influenzae + + Ø Ø + + Staph. epidermidis + + + Ø + + Ent. faecalis (VRE) + Ø Ø Ø + + Ent. casseliflavus + Ø Ø Ø + + (VRE) +M = antibacterial effect on Mueller Hinton Agar; + = effect on both plates (Muller Hinton Agar, Muller Hinton Agar with 5% sheep blood), (+) = effect on one plate -
-
TABLE 5 Quantification of the hydrolysates obtained for the plant drugs mentioned in Table 1 as well as the 5-plant extract against the pathogens listed in Table 1 using a spiral platter. All solutions were measured in 1:20 dilutions. Gentiana Sambucus Verbena Primula 5-plant l. n. o. v. extract Staph. aureus (+) (+) + +++ (+) P. aeruginosa ++++ +++ ++++ ++++ ++++ Pneumococcus +++ + (+) ++++ Strept. pyogenes ++++ ++++ ++++ ++++ ++++ Klebsiella +++ ++ ++ +++ +++ E. coli +++ (+) (+) + + H. influenzae ++++ ++++ ++++ ++++ ++++ Staph. +++ +++ +++ ++++ +++ epidermidis Ent. +++ ++ + +++ +++ faecalis (VRE) Ent. +++ ++ +++ +++ +++ casseliflavus (VRE) ++++ = 102 cfu/ml after 0 h, +++ = 102 cfu/ml after 4 h, ++ = 102 cfu/ml after 8 h, + = 103-104 cfu/ml after 8 h, (+) = higher activity compared to control group -
-
TABLE 6 Study regarding the reproducibility of the antibacterial effect of several extracts of the same individual drugs (Sambucus nigra, Gentiana lutea, Primula veris). Quantification using spiral platter in 1:20 dilution of the sample. Sambucus n. Extract 1 Extract 2 Extract 3 Staph. aureus (+) (+) (+) P. aeruginosa +++ +++ ++++ Pneumococcus + ++ ++ Strept. pyogenes ++++ +++ +++ Klebsiella ++ (+) +++ E. coli (+) (+) H. influenzae ++++ ++++ Staph. epidermidis +++ ++ ++++ Ent. faecalis (VRE) ++ (+) ++ Ent. casseliflavus (VRE) ++ ++ +++ Gentiana l. Extract 1 Extract 2 Extract 3 Staph. aureus (+) (+) (+) P. aeruginosa ++++ ++++ ++++ Pneumococcus +++ ++++ ++++ Strept. pyogenes ++++ ++++ ++++ Klebsiella +++ +++ ++++ E. coli +++ + ++++ H. influenzae ++++ ++++ ++++ Staph. epidermidis +++ +++ ++++ Ent. faecalis (VRE) +++ ++ +++ Ent. casseliflavus (VRE) +++ +++ ++++ Ex- Ex- Ex- Ex- Ex- Primula v. tract 1 tract 2 tract 3 tract 4 tract 5 Staph. aureus +++ (+) ++ (+) + P. aeruginosa ++++ +++ ++++ ++++ ++++ Pneumococcus ++++ (+) +++ +++ +++ Strept. pyogenes ++++ +++ ++++ ++++ +++ Klebsiella +++ (+) ++++ + +++ E. coli + (+) +++ ++ + H. influenzae ++++ +++ ++++ ++++ ++++ Staph. epidermidis ++++ (+) +++ +++ +++ Ent. faecalis +++ (+) +++ + + (VRE) Ent. +++ ++ +++ +++ ++ casseliflavus (VRE) ++++ = 102 cfu/ml after 0 h, +++ = 102 cfu/ml after 4 h, ++ = 102 cfu/ml after 8 h, + = 103-104 cfu/ml after 8 h, (+) = higher activity compared to control group
Claims (20)
1. A hydrolysate made of at least one extract, which is produced by:
extraction using ethanol/water from dried plant material selected from:
a) one or more of the plants selected from the group consisting of: Verbena officinalis L., Sambucus nigra L., Primula veris L., Primula elatior (L.) Hill and Gentian lutea L.; or
b) a mixture of: Verbena officinalis L., Sambucus nigra L., Primula veris L., Gentiana lutea L. and Rumicis herba;
subsequent removal of the ethanol/water extraction agent, and
hydrolytic treatment of the extract using a mineral acid.
2. The hydrolysate according to claim 1 , wherein the extract is produced from the plant material using an extraction agent made of 50% by volume ethanol and 50% by volume water over 6 hours to 36 hours, while stirring and subsequently vacuum evaporating the solvent.
3. The hydrolysate according to claim 1 , wherein the hydrolysate is obtained by the hydrolytic treatment of the plant extracts with hydrochloric acid as the mineral acid having a concentration of 1 M to 10 M at 80° C. to 100° C. for 30 minutes to 120 minutes.
4. The hydrolysate according to claim 3 , wherein the hydrolytic treatment of the extracts is carried out in the presence of ethanol or ethanol diluted with water.
5. A hydrolysate according to claim 1 , wherein the hydrolysate is evaporated to dryness for producing a dry extract and optionally neutralized.
6. A hydrolysate according to claim 1 , wherein the plant material for producing the dry extract stems from the following plant components:
a) Rumicis herba (Rumex acetosa L., Rumex acetosella L., Rumex obtusifolius L., Rumex patientia L. and Rumex crispus I.): leaves and stems;
b) Verbena officinalis: leaves and upper stem sections;
c) Sambucus nigra: blossoms;
d) Primula veris and/or Primula eliator: blossoms and capsules; and
e) Gentiana lutea: roots.
7. The hydrolysate according to claim 6 , wherein the dry extract comprises a mixture of Gentiana lutea: roots, Rumicis herba: leaves and stems, Verbena officinalis: leaves and upper stem sections, Sambucus nigra: blossoms, and Primula veris: blossoms and capsules, wherein the individual drugs are present in a mass ratio of 1:1:1:1:1 to 1:3:3:3:3.
8. A hydrolysate according to claim 1 , wherein the hydrolysate exhibits an antibacterial effect.
9. The hydrolysate according to claim 8 , wherein the antibacterial effect is directed against skin, ENT and respiratory tract relevant bacteria and optionally wherein the bacteria are gram positive cocci, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus mutans, and/or gram negative rod bacteria, optionally Haemophilus influenzae.
10. The hydrolysate according to claim 9 , wherein the bacteria are selected from the group consisting of Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Streptococcus pneumoniae (DSMZ 20566), Streptococcus pyogenes (DSMZ 20565), Haemophilus influenzae (DSMZ 4690); Enterococcus casseliflavus (DSMZ 20680); Pseudomonas aeruginosa (ATCC 27853); Klebsiella pneumoniae (ATCC 13883); E. coli; Enterococcus faecalis; and mixtures thereof.
11. A hydrolysate according to claim 1 , wherein it is effective for the protection and/or treatment of infections orally or topically on the skin and mucous membranes and is in the form of a galenic formulation.
12. An oral formulation comprising the hydrolysate according to claim 11 , wherein the oral formulation is in the form of sugar-coated tablets, tablets, film-coated tablets, capsules, liquid dilutions, drops, oral solutions or syrups.
13. An article used for topical applications comprising the hydrolysate according to claim 11 , wherein the article is a spray, ointment, emulsion, powder, liquid or solid preparation for inhalation, compress, wound and gum dressing, tamponade, tonsil brush solution, gargling solution, or rinsing solution for the nose and ears
14. A tamponade used for dental applications, further comprising the hydrolysate according to claim 11 .
15. The article according to claim 13 , wherein the rinsing solutions for the nose and ears are present in combination with physiological or hyperosmolar concentrations of salts or salt mixtures.
16. The hydrolysate according to claim 1 , wherein the hydrolysate is in the form of a lyophilisate.
17. An antibacterial agent comprising a hydrolysate according to claim 1 .
18. The antibacterial agent according to claim 17 , wherein the antibacterial agent further comprises pharmaceutically common adjuvants.
19. A retard formulation comprising the antibacterial agent according to claim 17 .
20. An oral formulation comprising the hydrolysate according to claim 11 , wherein the oral formulation is in the form of drops, oral solutions or syrups.
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