AT413334B - Medically usable solid dosage form comprises freeze-dried live lactic acid bacteria and an excipient powder mixture of inulin and lactose in the form of a directly compressed tablet - Google Patents
Medically usable solid dosage form comprises freeze-dried live lactic acid bacteria and an excipient powder mixture of inulin and lactose in the form of a directly compressed tablet Download PDFInfo
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- AT413334B AT413334B AT19272002A AT19272002A AT413334B AT 413334 B AT413334 B AT 413334B AT 19272002 A AT19272002 A AT 19272002A AT 19272002 A AT19272002 A AT 19272002A AT 413334 B AT413334 B AT 413334B
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- Prior art keywords
- lactic acid
- acid bacteria
- solid dosage
- inulin
- lactose
- Prior art date
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- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims abstract description 26
- 241000894006 Bacteria Species 0.000 title claims abstract description 17
- 239000004310 lactic acid Substances 0.000 title claims abstract description 16
- 235000014655 lactic acid Nutrition 0.000 title claims abstract description 16
- 229920001202 Inulin Polymers 0.000 title claims abstract description 9
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 title claims abstract description 9
- 229940029339 inulin Drugs 0.000 title claims abstract description 9
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 title claims abstract description 8
- 239000008101 lactose Substances 0.000 title claims abstract description 8
- 239000000546 pharmaceutical excipient Substances 0.000 title claims abstract description 8
- 239000007909 solid dosage form Substances 0.000 title claims abstract description 8
- 239000007891 compressed tablet Substances 0.000 title claims abstract 3
- 239000000843 powder Substances 0.000 title claims abstract 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 title abstract description 6
- 239000003826 tablet Substances 0.000 claims abstract description 38
- 238000009505 enteric coating Methods 0.000 claims abstract 3
- 239000002702 enteric coating Substances 0.000 claims abstract 3
- 240000001046 Lactobacillus acidophilus Species 0.000 claims description 13
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 claims description 13
- 229940039695 lactobacillus acidophilus Drugs 0.000 claims description 13
- 238000009472 formulation Methods 0.000 claims description 4
- 125000000129 anionic group Chemical group 0.000 claims 1
- 239000007888 film coating Substances 0.000 claims 1
- 238000009501 film coating Methods 0.000 claims 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims 1
- 125000005397 methacrylic acid ester group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 238000001035 drying Methods 0.000 abstract description 2
- 230000010534 mechanism of action Effects 0.000 abstract 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 22
- 239000000463 material Substances 0.000 description 12
- 239000000454 talc Substances 0.000 description 12
- 235000012222 talc Nutrition 0.000 description 12
- 229910052623 talc Inorganic materials 0.000 description 12
- 235000019359 magnesium stearate Nutrition 0.000 description 11
- 230000000968 intestinal effect Effects 0.000 description 6
- 230000007774 longterm Effects 0.000 description 4
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 235000021107 fermented food Nutrition 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 230000007407 health benefit Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000021262 sour milk Nutrition 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229920003139 Eudragit® L 100 Polymers 0.000 description 1
- 229920003136 Eudragit® L polymer Polymers 0.000 description 1
- 229920003141 Eudragit® S 100 Polymers 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 235000014048 cultured milk product Nutrition 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 235000015141 kefir Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
22
AT 413 334 BAT 413 334 B
Die vorliegende Erfindung betrifft feste Darreichungsformen mit lebenden Milchsäurebakterien.The present invention relates to solid dosage forms with living lactic acid bacteria.
Seit Jahrhunderten wird der Verzehr von fermentierten Lebensmitteln und vor allem von Sauermilchprodukten mit einem vielfältigen Nutzen für die Gesundheit des Menschen verknüpft. 5 Neben der Herstellung von fermentierten Sauermilchprodukten (Joghurt, Kefir und Frischkäse) werden Milchsäurebakterien als Biokonservierungsmittel (Fleisch, Brot) und zur Herstellung von fermentierten Lebensmitteln (fermentierte Wurst, Brot) eingesetzt. Sie liefern wichtige Vitamine (Vitamin C und B) und Enzyme (beta-Galactosidase) und können darüber hinaus durch aromabildende und konsistenzgebende Eigenschaften die Nahrung verbessern. 10For centuries, the consumption of fermented foods, and especially of sour milk products, has been linked to a variety of human health benefits. 5 In addition to the production of fermented sour milk products (yoghurt, kefir and cream cheese), lactic acid bacteria are used as bioconservatives (meat, bread) and for the production of fermented foods (fermented sausages, bread). They provide important vitamins (vitamins C and B) and enzymes (beta-galactosidase) and, in addition, can improve nutrition through their aroma-forming and restorative properties. 10
In den letzten zwei Jahrzehnten wurde eingehend die mögliche probiotische Wirkung durch den Verzehr von fermentierten Milchprodukten und den darin enthaltenden Milchsäurebakterien untersucht. 15 Unter "Probiotika" werden Nahrungsmittelzusätze verstanden, die lebende Mikroorganismen enthalten, die das Verhältnis intestinaler Mikroorganismen zueinander so beeinflussen, daß ein gesundheitlicher Nutzen für Mensch und Tier erwächst.In the last two decades, the potential probiotic effect of consuming fermented milk products and the lactic acid bacteria contained therein has been studied in detail. 15 " Probiotics " Food supplements are understood to contain living microorganisms that influence the relationship of intestinal microorganisms to one another in such a way that a health benefit for humans and animals is produced.
Aus den Patentveröffentlichungen WO 01/95918, WO 97/07822 und JP 4041434 sind Tabletten 20 mit getrockneten Milchsäurebakterien bekannt. Inulin und Lactose zählen zu den bekannten Preßhilfsstoffen und werden beispielsweise in den zuvor angeführten WO-Veröffentlichungen sowie in WO 98/46261 erwähnt. Die bekannten Tabletten mit einem Gehalt an lebenden Milchsäurebakterien lassen jedoch noch Raum für weitere Verbesserungen. 25 Ziel der Erfindung ist es, optimierte Tablettenmuster hinsichtlich Magensaftresistenz und Verhalten im artifiziellen Darmsaft zu schaffen und Langzeitstudien zur Ermittlung der Stabilität bei verschiedenen Temperaturstufen durchzuführen. Im speziellen sollte eine einfache, preiswerte und medizinisch verwendbare Applikationsform entwickelt werden. 30 Diese Ziele werden erfindungsgemäß mit den in den Ansprüchen gekennzeichneten Merkmalen erreicht.From the patent publications WO 01/95918, WO 97/07822 and JP 4041434 are known tablets 20 with dried lactic acid bacteria. Inulin and lactose are among the known pressing adjuvants and are mentioned, for example, in the previously cited WO publications and in WO 98/46261. However, the known tablets containing live lactic acid bacteria still leave room for further improvements. 25 The aim of the invention is to provide optimized tablet patterns in terms of enteric resistance and behavior in the artificial intestinal juice and to carry out long-term studies to determine the stability at different temperature levels. In particular, a simple, inexpensive and medically usable form of application should be developed. These objects are achieved according to the invention with the features characterized in the claims.
Hiezu wurden zwölf Milchsäurebakterien enthaltende Tablettenrezepturen entwickelt, die in 35 weiterer Folge als "Tablette 1" bis "Tablette 12" bezeichnet werden. Zusammensetzung der Tabletten 1 Material Menge (Gew.-%) Inulin 89,00 40 Lactobacillus acidophilus 74-2 10,00 Talkum 0,90 Magnesiumstearat 0,10 Zusammensetzung der Tabletten 2 45 Material Menge (Gew.-%) Eudragit® L100 89,00 Lactobacillus acidophilus 74-2 10,00 Talkum 0,90 50 Magnesiumstearat 0,10 Zusammensetzung der Tabletten 3 Material Menge (Gew.-%) Calciumhydrogenphosphat-Dihydrat 70,00 Avicel® PH. 101 19,00 55 Lactobacillus acidophilus 74-2 10,00 3To this end, twelve tablet formulations containing lactic acid bacteria were developed, which in further succession became known as " Tablet 1 " until " tablet 12 " be designated. Composition of the tablets 1 Material Amount (% by weight) Inulin 89.00 40 Lactobacillus acidophilus 74-2 10.00 Talc 0.90 Magnesium stearate 0.10 Composition of the tablets 2 45 Material Amount (% by weight) Eudragit® L100 89 , 00 Lactobacillus acidophilus 74-2 10.00 Talc 0.90 50 Magnesium stearate 0.10 Composition of the tablets 3 Material Quantity (% by weight) Calcium hydrogen phosphate dihydrate 70.00 Avicel® PH. 101 19,00 55 Lactobacillus acidophilus 74-2 10,00 3
AT 413 334 BAT 413 334 B
Talkum 0,90Talc 0.90
Magnesiumstearat 0,10Magnesium stearate 0.10
Menge (Gew.-%) 89.00 10.00 0,90 0,10Quantity (% by weight) 89.00 10.00 0.90 0.10
Menge (Gew.-%) 89.00 10.00 0,90 0,10Quantity (% by weight) 89.00 10.00 0.90 0.10
Zusammensetzung der Tabletten 4 5 Material MicroceLac®Composition of the tablets 4 5 Material MicroceLac®
Lactobacillus acidophilus 74-2 TalkumLactobacillus acidophilus 74-2 talc
Magnesiumstearat 10Magnesium Stearate 10
Zusammensetzung der Tabletten 5Composition of the tablets 5
Materialmaterial
Avicel® PH 101Avicel® PH 101
Lactobacillus acidophilus 74-2 15 TalkumLactobacillus acidophilus 74-2 15 talc
Magnesiumstearatmagnesium stearate
Zusammensetzung der Tabletten 6Composition of the tablets 6
Material Menge (Gew.-%) 20 Maisstärke Star-X® 89,00Material Quantity (% by weight) 20 Corn starch Star-X® 89,00
Lactobacillus acidophilus 74-2 10,00Lactobacillus acidophilus 74-2 10.00
Talkum 0,90Talc 0.90
Magnesiumstearat 0,10 25 Zusammensetzung der Tabletten 7 Material Hydroxypropylmethylcelluloseacetatsuccinat Lactobacillus acidophilus 74-2 Talkum 30 Magnesiumstearat Zusammensetzung der Tabletten 8 Material Hydroxypropylmethylcellulosephthalat HP-55 35 Lactobacillus acidophilus 74-2 Talkum Magnesiumstearat Zusammensetzung der Tabletten 9Magnesium stearate 0.10 25 Composition of tablets 7 Material Hydroxypropylmethylcellulose acetate succinate Lactobacillus acidophilus 74-2 Talc 30 Magnesium stearate Composition of tablets 8 Material Hydroxypropylmethylcellulose phthalate HP-55 35 Lactobacillus acidophilus 74-2 Talc Magnesium stearate Composition of tablets 9
Menge (Gew.-%) 89.00 10.00 0,90 0,10Quantity (% by weight) 89.00 10.00 0.90 0.10
Menge (Gew.-%) 89.00 10.00 0,90 0,10 40 Material Menge (Gew.-%) Inulin 79,00 Lactobacillus acidophilus 74-2 10,00 Lactose 10,00 Talkum 0,90 45 Magnesiumstearat 0,10Amount (wt.%) 89.00 10.00 0.90 0.10 40 Material Amount (wt.%) Inulin 79.00 Lactobacillus acidophilus 74-2 10.00 Lactose 10.00 Talc 0.90 45 Magnesium stearate 0.10
Zusammensetzung der Tabletten 10Composition of the tablets 10
Material Menge (Gew.-%)Material quantity (wt .-%)
Maisstärke Star-X® 88,00 so Lactobacillus acidophilus 74-2 10,00Corn starch Star-X® 88.00 Sun Lactobacillus acidophilus 74-2 10.00
Aerosil® 200 1,00Aerosil® 200 1.00
Talkum 0,90Talc 0.90
Magnesiumstearat 0,10 55Magnesium Stearate 0.10 55
Zusammensetzung der Tabletten 11 4Composition of the tablets 11 4
AT 413 334 BAT 413 334 B
Menge (Gew.-%) 89.00 10.00 0,90 0,10Quantity (% by weight) 89.00 10.00 0.90 0.10
Menge (Gew.-%) 99,00 0,50 0,50Amount (% by weight) 99.00 0.50 0.50
Material Eudragit® S100 Lactobacillus acidophilus 74-2 Talkum 5 MagnesiumstearatMaterial Eudragit® S100 Lactobacillus acidophilus 74-2 talcum 5 magnesium stearate
Zusammensetzung der Tabletten 12 MaterialComposition of the tablets 12 material
Lactobacillus acidophilus 74-2 io Talkum Λ Λ m η ΪΙ®Lactobacillus acidophilus 74-2 io talcum Λ Λ m η ΪΙ®
AerosilAerosil
Zur Herstellung der Tabletten wurde im wesentlichen wie folgt vorgegangen: Die Hilfsstoffe wurden in der Reibschale gut vermengt. Die Tablettenvormischungen wurden laut Rezeptur 1 15 bis 11 eingewogen und anschließend über Nacht im Trockenschrank bei 60°C getrocknet. Danach wurde das Milchsäurebakterien-Lyophilisat (10% Anteil) zugesetzt und die Mischung wurde im Kubusmischer 30 Minuten lang gemischt. Zur Verbesserung der Lagerstabilität der Milchsäurebakterien wurden die einzelnen Hilfsstoffe vorgetrocknet. Dadurch kann durch Feuchtigkeit verursachtes Auskeimen der Milchsäurebakterien verhindert werden. Anschließend 20 wurden die Tablettenmischungen auf einer Exzenterpresse mit unterschiedlicher Preßkraft zu Tabletten gepreßt.The tablets were prepared essentially as follows: The excipients were well mixed in the mortar. The tablet premixes were weighed according to recipe 1 15 to 11 and then dried overnight in a drying oven at 60 ° C. Thereafter, the lactic acid bacteria lyophilizate (10% portion) was added and the mixture was mixed in the cube mixer for 30 minutes. To improve the storage stability of the lactic acid bacteria, the individual adjuvants were predried. As a result, moisture-induced germination of the lactic acid bacteria can be prevented. Subsequently, the tablet mixtures were pressed on an eccentric press with different pressing force into tablets.
Zur Stabilitätsprüfung der Tabletten wurde durch Langzeitstudien die Überlebensrate der Milchsäurebakterien von ausgewählten Tabletten unter Temperaturbelastung ermittelt. Zu diesem 25 Zweck wurden die Tabletten 1 bis 11 unter Lichtschutz im Kühlschrank bei 10°C und in Wärmeschränken bei 20 und 30°C gelagert.To test the stability of the tablets, the survival rate of the lactic acid bacteria of selected tablets under temperature load was determined by long-term studies. For this purpose, tablets 1 to 11 were stored under light protection in the refrigerator at 10 ° C and in warming cabinets at 20 and 30 ° C.
Weiterhin wurde die Tablettenzerfallbarkeit in künstlichem Darmsaft überprüft, wobei während der Prüfdauer eine mögliche auftretende Keimzahlerniedrigung geprüft wurde. Dabei ergab 30 sich, daß insbesondere bei den Tabletten 1, 3 und 9 eine gute Magensaftresistenz nachgewiesen werden konnte. Die geringsten Keimzahlverluste wurden bei Tabletten gemäß Rezeptur 9 (Inulin und Lactose als Hilfsstoffgemisch) sowohl bei den Langzeitstabilitätstests als auch bei der simulierten Magen- und Darmpassage gefunden. 35 Bei einer Preßkraft von 4, 8, 25 und 50 kN wurden biplanare Tabletten mit einem Durchmesser von 10 mm und unterschiedlichem Tablettengewicht angefertigt. Je größer die Preßkraft war, desto größer war auch die Keimzahlreduktion. Allen Tablettenrezepturen war gemeinsam, daß bei einer Preßkraft von 4 und 8 kN eine Keimzahlreduktion von maximal 0,5 log-Einheiten gefunden werden konnte. 40Furthermore, the tablet disintegratability was checked in artificial intestinal juice, during the test period a possible germ reduction was examined. It was found that, in particular in the case of tablets 1, 3 and 9, a good resistance to gastric juice could be detected. The lowest number of microbial losses were found in tablets according to formulation 9 (inulin and lactose as excipient mixture) both in the long-term stability tests and in the simulated gastric and intestinal passage. 35 With a force of 4, 8, 25 and 50 kN biplanar tablets with a diameter of 10 mm and different tablet weights were made. The greater the pressing force was, the larger the germ count reduction was. All tablet recipes had in common that at a pressing force of 4 and 8 kN a number reduction of a maximum of 0.5 log units could be found. 40
Die geringsten Keimzahlverluste wurden bei Tabletten gemäß Rezeptur 9 (Inulin und Lactose als Hilfsstoffgemisch) sowohl bei den Langzeitstabilitätstests als auch bei der simulierten Magen- und Darmpassage gefunden. 45 Alle Tabletten zeigten nach ein- bzw. zweistündiger Inkubation in 0,1 N Salzsäure eine ausreichende Magensaftresistenz. Nach 20 Minuten im artifiziellen Darmsaft waren alle Tabletten zerfallen. Der rasche Zerfall stellt eine Voraussetzung der Wirksamkeit dar.The lowest number of microbial losses were found in tablets according to formulation 9 (inulin and lactose as excipient mixture) both in the long-term stability tests and in the simulated gastric and intestinal passage. All tablets showed adequate gastric juice resistance after incubation in 0.1 N hydrochloric acid for one or two hours. After 20 minutes in the artificial intestinal juice, all the tablets had disintegrated. Rapid disintegration is a prerequisite for effectiveness.
Insgesamt hat sich gezeigt, daß die mit Eudragit® L-Filmlackrezeptur überzogenen Lyo-50 Tabletten und die mit Inulin und Lactose hergestellten Tabletten in Hinsicht auf die Lagerfähigkeit und Magensaftresistenz die besten Ergebnisse aufweisen. 55Overall, it has been found that the Lyo-50 tablets coated with Eudragit® L film paint formulation and the tablets prepared with inulin and lactose have the best results in terms of shelf life and gastroresistant resistance. 55
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT19272002A AT413334B (en) | 2002-12-23 | 2002-12-23 | Medically usable solid dosage form comprises freeze-dried live lactic acid bacteria and an excipient powder mixture of inulin and lactose in the form of a directly compressed tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT19272002A AT413334B (en) | 2002-12-23 | 2002-12-23 | Medically usable solid dosage form comprises freeze-dried live lactic acid bacteria and an excipient powder mixture of inulin and lactose in the form of a directly compressed tablet |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ATA19272002A ATA19272002A (en) | 2005-07-15 |
| AT413334B true AT413334B (en) | 2006-02-15 |
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| Application Number | Title | Priority Date | Filing Date |
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| AT19272002A AT413334B (en) | 2002-12-23 | 2002-12-23 | Medically usable solid dosage form comprises freeze-dried live lactic acid bacteria and an excipient powder mixture of inulin and lactose in the form of a directly compressed tablet |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104095180A (en) * | 2013-04-12 | 2014-10-15 | 中国科学院烟台海岸带研究所 | Probiotics inulin sheet and preparation method thereof |
| CN109363183A (en) * | 2018-12-11 | 2019-02-22 | 大连民族大学 | A kind of inulin probiotic companion and preparation method thereof |
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| JPH0441434A (en) * | 1990-06-07 | 1992-02-12 | Asahi Breweries Ltd | Lactobacillus tablet provided with enteric coating |
| JPH08188535A (en) * | 1995-01-06 | 1996-07-23 | Kurorera Kogyo Kk | Probiotics |
| WO1997007822A1 (en) * | 1995-08-25 | 1997-03-06 | Wasa Medicals Ab | Method for the production of tablets by pressing and tablets produced by the method |
| WO1998046261A1 (en) * | 1997-04-11 | 1998-10-22 | Gynelogix, Inc. | Vaginal lactobacillus medicant |
| HU215970B (en) * | 1994-12-09 | 1999-04-28 | Balázs Dolhay | Solide water-soluble composition for producing solutions for vaginal irrigation |
| WO2001095918A1 (en) * | 2000-06-13 | 2001-12-20 | Yves Delatte | A process for producing and packaging lactic acid bacteria tablets |
| DE20202562U1 (en) * | 2002-02-19 | 2002-05-23 | Orthomol pharmazeutische Vertriebs GmbH, 40764 Langenfeld | Micronutrient combination product with probiotics and prebiotics |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0441434A (en) * | 1990-06-07 | 1992-02-12 | Asahi Breweries Ltd | Lactobacillus tablet provided with enteric coating |
| HU215970B (en) * | 1994-12-09 | 1999-04-28 | Balázs Dolhay | Solide water-soluble composition for producing solutions for vaginal irrigation |
| JPH08188535A (en) * | 1995-01-06 | 1996-07-23 | Kurorera Kogyo Kk | Probiotics |
| WO1997007822A1 (en) * | 1995-08-25 | 1997-03-06 | Wasa Medicals Ab | Method for the production of tablets by pressing and tablets produced by the method |
| WO1998046261A1 (en) * | 1997-04-11 | 1998-10-22 | Gynelogix, Inc. | Vaginal lactobacillus medicant |
| WO2001095918A1 (en) * | 2000-06-13 | 2001-12-20 | Yves Delatte | A process for producing and packaging lactic acid bacteria tablets |
| DE20202562U1 (en) * | 2002-02-19 | 2002-05-23 | Orthomol pharmazeutische Vertriebs GmbH, 40764 Langenfeld | Micronutrient combination product with probiotics and prebiotics |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104095180A (en) * | 2013-04-12 | 2014-10-15 | 中国科学院烟台海岸带研究所 | Probiotics inulin sheet and preparation method thereof |
| CN109363183A (en) * | 2018-12-11 | 2019-02-22 | 大连民族大学 | A kind of inulin probiotic companion and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| ATA19272002A (en) | 2005-07-15 |
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