SE465905B - DENTALS CONTAINING AN ACETATE OR GLUCONATE SALT OF AN ANTIMICROBIAL BISBIGUANIDE - Google Patents
DENTALS CONTAINING AN ACETATE OR GLUCONATE SALT OF AN ANTIMICROBIAL BISBIGUANIDEInfo
- Publication number
- SE465905B SE465905B SE8900915A SE8900915A SE465905B SE 465905 B SE465905 B SE 465905B SE 8900915 A SE8900915 A SE 8900915A SE 8900915 A SE8900915 A SE 8900915A SE 465905 B SE465905 B SE 465905B
- Authority
- SE
- Sweden
- Prior art keywords
- acetate
- copper
- bisbiguanide
- gluconate
- chlorhexidine
- Prior art date
Links
- 150000004287 bisbiguanides Chemical class 0.000 title claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 title claims description 9
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 title claims description 9
- 230000000845 anti-microbial effect Effects 0.000 title claims description 6
- 239000004599 antimicrobial Substances 0.000 title claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical group [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 23
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 claims description 20
- 229960003260 chlorhexidine Drugs 0.000 claims description 19
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical compound [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 claims description 8
- 229940108925 copper gluconate Drugs 0.000 claims description 8
- 229940050410 gluconate Drugs 0.000 claims description 6
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical class [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 5
- 239000000606 toothpaste Substances 0.000 claims description 5
- 229940034610 toothpaste Drugs 0.000 claims description 5
- 229940112822 chewing gum Drugs 0.000 claims description 4
- 235000015218 chewing gum Nutrition 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 238000002845 discoloration Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 6
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 5
- 229960003333 chlorhexidine gluconate Drugs 0.000 description 5
- -1 bisbiguanide salts Chemical class 0.000 description 4
- 239000000551 dentifrice Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 150000001879 copper Chemical class 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 241000186044 Actinomyces viscosus Species 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 230000017066 negative regulation of growth Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000001974 tryptic soy broth Substances 0.000 description 2
- 108010050327 trypticase-soy broth Proteins 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000014151 Stomatognathic disease Diseases 0.000 description 1
- 241000194019 Streptococcus mutans Species 0.000 description 1
- 241000122143 Streptococcus mutans serotype C Species 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 229910052976 metal sulfide Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004354 sulfur functional group Chemical group 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/43—Guanidines
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
465 905 2 Klorhexidin förhindrar också utvecklingen av redan uppkomna tandsjukdomar. Förutom att användas i sköljvätskor, kan klorhex- idin också användas i form av tandpasta eller gel för tandborst- ning, med samma effekt som tidigare angivits. 465 905 2 Chlorhexidine also prevents the development of already existing dental diseases. In addition to being used in rinsing liquids, chlorhexidine can also be used in the form of toothpaste or gel for brushing teeth, with the same effect as previously stated.
Man skulle tro att, på grund av de ovannämnda fördelaktiga egenskaperna, dessa klorhexidinsalter och liknande bisbiguanider borde ha funnit en omfattande användning inom odontologi och tandvård. En allvarlig begränsning med dessa preparat är emel- lertid den betydande missfärgning av tänderna som uppstår vid användning av klorhexidin eller andra liknande bisbiguanidsalter efter en viss tid. Missfärgningen uppstår särskilt mellan tän- derna, är mörkbrun till svart i färgen, och svår att avlägsna på grund av att den är förkalkad. Missfärgningen består troligen av förkalkat pellikelprotein som är missfärgat av metallsulfider, speciellt järn, som kommer från kosten. Missfärgningen uppstår sannolikt genom att pellikelproteinet, som täcker tandytorna med ett tunt skikt denatureras av bisbiguaniden. Därefter binder blottlagda svavelgrupper metaller som således missfärgas, var- efter hela pellikelmassan förkalkas på längre sikt.It would be believed that, due to the above beneficial properties, these chlorhexidine salts and similar bisbiguanides should have found widespread use in dentistry and dentistry. A serious limitation with these preparations, however, is the significant discoloration of the teeth which occurs with the use of chlorhexidine or other similar bisbiguanide salts after a certain time. The discoloration occurs especially between the teeth, is dark brown to black in color, and difficult to remove because it is calcified. The discoloration probably consists of calcified pellicle protein which is discolored by metal sulphides, especially iron, which comes from the diet. The discoloration is likely to be caused by the pellicle protein, which covers the tooth surfaces with a thin layer, being denatured by the bisbiguanide. Thereafter, exposed sulfur groups bind metals which are thus discolored, after which the entire pellicle mass is calcified in the longer term.
Det har länge varit ett önskemål att kunna utnyttja de goda plackhämmande egenskaperna hos klorhexidin och andra bisbigua- nidsalter samtidigt som den ovannämnda missfärgningen undvikes.It has long been a desire to be able to utilize the good plaque-inhibiting properties of chlorhexidine and other bisbiguanide salts while avoiding the above-mentioned discoloration.
Förhindring av missfärgning av tänderna får således icke ske på bekostnad av den antimikrobiella effekten.Thus, the discoloration of the teeth must not be prevented at the expense of the antimicrobial effect.
Det har nu visat sig att de goda plack-hämmande egenskaperna hos bisbiguanidsalter, såsom klorhexidin, i sin helhet kan utnyttjas samt uppkomsten av missfärgningar på tänderna reduce- ras om man till ett tandvårdsmedel, såsom en tandkräm, lösning, tablett, eller tuggummi, som innehåller ett acetat- eller gluko- natsalt av en antimikrobiell bisbiguanid, också sätter ett vattenlösligt, fysiologiskt godtagbart koppar(II)salt.It has now been found that the good plaque-inhibiting properties of bisbiguanide salts, such as chlorhexidine, can be utilized in their entirety and the occurrence of discoloration on the teeth is reduced if one uses a dentifrice, such as a toothpaste, solution, tablet, or chewing gum, contains an acetate or gluconate salt of an antimicrobial bisbiguanide, also adds a water-soluble, physiologically acceptable copper (II) salt.
Det har också överraskande visat sig att en kombination av bisbiguanid och koppar(II)salt såsom kopparacetat eller koppar- glukonat ger en synergistisk plackhämmande effekt, samtidigt som uppkomsten av missfärgningar är ringa och av en sådan karaktär att de lätt kan borstas bort av patienten medelst tandborstning vilket ej är möjligt vid missfärgningar som uppkommer i samband med användning av klorhexidin enbart.It has also surprisingly been found that a combination of bisbiguanide and copper (II) salt such as copper acetate or copper gluconate has a synergistic plaque inhibitory effect, while the appearance of discolorations is small and of such a nature that they can be easily brushed off by the patient by toothbrushing which is not possible for discolorations that occur in connection with the use of chlorhexidine alone.
För att åskådliggöra effekten av ett tandvårdsmedel enligt 3 465 905 uppfinningen framställdes en lösning innehållande 0,05 vikt-% klorhexidin och 0,04 vikt-% kopparacetat. En grupp på 15 friska försökspersoner deltog i en dubbel-blind cross over studie, där varje försöksperson deltog i tre studier som var och en varade i 3 veckor. Under varje treveckorsperiod utförde försökspersonerna ingen munhygien. Som positiv kontroll sköljde försökspersonerna med en 0,12 vikt% klorhexidinlösning i tre veckor och som nega- tiv kontroll sköljde de med fysiologisk koksaltlösning. Plack- och gingivalindex blev registrerat enligt kliniska standardme- toder, (Loe, H., J. of Periodontology 38:6l0-616, 1965, Loe, H., Theilade, E. och Jensen, S.B., J. of Periodontology 36:177-187, 1965). Resultatet av undersökningen har sammanställts i nedan- stående tabell 465 905 4 TABELL Försöks- Plackindex Gingivalindex person mfimminT- ** 3~51Y3ï°1°9ï3k Klorheßcidin* Klorhæcidin" Fysio- och Hfififl och käfl* nqqaraxnac _ mqgmnæxmac Hflfll 1 0,60 0,95 1,00 0,56 0,76 0,95 2 1,12 0,90 1,03 0,09 0,09 1,00 3 0,65 1,42 1,75 0,95 1,23 1,52 4 0,09 0,71 1,62 0,91 0,77 1,11 5 0,60 0,96 1,75 1,32 1,24 1,30 6 0,09 0 0,67 1,70 1,03 1,21 1,16 7 0,39 0,52 1,27 0,75 0,70 1,27 0 1,02 0,40 1,54 0,30 0,35 0,30 9 0,50 0,71 1,51 1,12 1,03 1,21 10 0,06 0,90 1,47 1,32 1,14 1,05 11 1,04 1,27 1,75 0,07 1,05 1,00 12 0,54 1,10 1,06 1,03 1,56 1,49 13 0,70 0,56 1,59 1,13 1,13 1,06 14 0,35 0,01 0,91 1,09 15 ~ I 1602160550 _ 0,74 0,07 1,59 0,94 1,01 1,12 X * lösning av 0.12 viktæ klornexiain 1 11,6 viktæ alkohol, pa 5,5 UPERIDEX” från Procter and Gamble) ** lösning av 0,04 vikt% koppar(II)acetat och 0,05 vikt% kloçhexidin i destillerat vatten framställd av 20% klorhexidinglukonat PHIBITANE” ) 5 465 905 Härav framgår att lösningen av klorhexidin och kopparacetat vad gäller inhibering av plackbildningen var jämförbar med lös- ningen av enbart klorhexidin, som förelåg i mer än den dubbla koncentrationen.To illustrate the effect of a dentifrice according to the invention, a solution containing 0.05 wt% chlorhexidine and 0.04 wt% copper acetate was prepared. A group of 15 healthy subjects participated in a double-blind cross-over study, where each subject participated in three studies, each lasting 3 weeks. During each three-week period, the subjects did not perform oral hygiene. As a positive control, the subjects rinsed with a 0.12% by weight chlorhexidine solution for three weeks and as a negative control, they rinsed with physiological saline. Plaque and gingival indices were recorded according to standard clinical methods, (Loe, H., J. of Periodontology 38: 610-616, 1965, Loe, H., Theilade, E. and Jensen, SB, J. of Periodontology 36: 177-187, 1965). The results of the study have been compiled in the following table 465 905 4 TABLE Experimental Plaque index Gingival index person m .95 1.00 0.56 0.76 0.95 2 1.12 0.90 1.03 0.09 0.09 1.00 3 0.65 1.42 1.75 0.95 1.23 1 , 52 4 0.09 0.71 1.62 0.91 0.77 1.11 5 0.60 0.96 1.75 1.32 1.24 1.30 6 0.09 0 0.67 1, 70 1.03 1.21 1.16 7 0.39 0.52 1.27 0.75 0.70 1.27 0 1.02 0.40 1.54 0.30 0.35 0.30 9 0 .50 0.71 1.51 1.12 1.03 1.21 10 0.06 0.90 1.47 1.32 1.14 1.05 11 1.04 1.27 1.75 0.07 1 .05 1.00 12 0.54 1.10 1.06 1.03 1.56 1.49 13 0.70 0.56 1.59 1.13 1.13 1.06 14 0.35 0.01 0.91 1.09 15 ~ I 1602160550 _ 0.74 0.07 1.59 0.94 1.01 1.12 X * solution of 0.12 wt. Chlornexiain 1 11.6 wt. Alcohol, pa 5.5 UPERIDEX ”from Procter and Gamble) ** solution of 0,04% by weight of copper (II) acetate and 0,05% by weight of clochexidine in distilled water prepared from 20% chlorhexidine gluconate PHIBITANE ') 5 465 905 The solution of chlorhexidine and copper acetate in inhibiting plaque formation was comparable to the solution of chlorhexidine alone, which was present in more than twice the concentration.
Dessa båda lösningar var i sin tur signifikant mer effektiva än salinlösningen. Det är vidare välkänt att en 0,05 % klorhexi- dinlösning ej ger någon klinisk effekt (Skorland et al, Scand.These two solutions were in turn significantly more effective than the saline solution. It is further well known that a 0.05% chlorhexidine solution has no clinical effect (Skorland et al, Scand.
J. Dent. Res. 86: 103-107, 1978).J. Dent. Res. 86: 103-107, 1978).
Den kliniska undersökningen gav också det överraskande resultatet att klorhexidin/kopparacetatlösningen gav mindre missfärgningar i jämförelse med ren klorhexidin och denna milda form av missfärgning kunde lätt avlägsnas med konventionell tandborstning.The clinical examination also gave the surprising result that the chlorhexidine / copper acetate solution gave less discoloration compared to pure chlorhexidine and this mild form of discoloration could be easily removed with conventional toothbrushing.
För att närmare belysa den synergistiska effekten mellan kop- paracetat och klorhexidin har mikrobiologiska försök in vitro utförts med Streptococcus mutans och Actinomyses viscosus, två mycket vanliga orala bakterier som anses väsentliga för uppkoms- ten av karies och parodontit. MIC (minimal inhibitory concentration) test utfördes med enbart klorhexidin eller kop- paracetat och olika kombinationer av dessa salter. Samtliga %-värden avser i det följande viktsprocent om ej annat anges.To further elucidate the synergistic effect between copper acetate and chlorhexidine, microbiological experiments have been performed in vitro with Streptococcus mutans and Actinomyses viscosus, two very common oral bacteria that are considered essential for the development of caries and periodontitis. MIC (minimal inhibitory concentration) test was performed with chlorhexidine or copper acetate alone and various combinations of these salts. All% values in the following refer to weight percent unless otherwise stated.
Streptococcus mutans serotyp C och Actinomyces viscosus isolat odlades i tryptikas sojabuljong (TSB) kompletterat med jästextrakt (YE) (0,5 %) i en 5 % C02-inkubator i 24 timmar. Kul- turerna skördades genom centrifugering, tvättades och resuspen- derades i TSB-YE av dubbla styrkan och ställdes på en lämplig optisk densitet under hänvisning till en förutbestämd standard- kurva. Seriespädningar av klorhexidinglukonat och kopparacetat gjordes i 0,15 M NaCl. Analysblandningarna utgjordes av en stan- dardiserad ymp av tvättade celler (slutkonc. 5 x 105 cfu/ml) och av samma volym av försöksföreningen. För bestämning av eventuell synergistisk effekt kombinerades olika koncentrationer av varje förening och ympades enligt ovan. Alla rör inkuberades i 24 h i 5 % C02 vid 37°C.Streptococcus mutans serotype C and Actinomyces viscosus isolate were grown in trypticase soy broth (TSB) supplemented with yeast extract (YE) (0.5%) in a 5% CO 2 incubator for 24 hours. The cultures were harvested by centrifugation, washed and resuspended in double strength TSB-YE and set to a suitable optical density with reference to a predetermined standard curve. Serial dilutions of chlorhexidine gluconate and copper acetate were made in 0.15 M NaCl. The assay mixtures consisted of a standardized inoculum of washed cells (final conc. 5 x 105 cfu / ml) and of the same volume of the test compound. To determine any synergistic effect, different concentrations of each compound were combined and inoculated as above. All tubes were incubated for 24 hours in 5% CO 2 at 37 ° C.
Resultaten framgår av figurerna 1 och 2. MIC-värdet för klorhexidin var 9,76 x 106% (vikt/volym) och för kopparacetat 0,02 % (vikt/volym).The results are shown in Figures 1 and 2. The MIC value for chlorhexidine was 9.76 x 106% (w / v) and for copper acetate 0.02% (w / v).
Vid den första serien av försök blandades olika koncentratio- ner av koppar(II)acetat med klorhexidinglukonat såsom visas i 465 905 6 Fig. 1. Den högsta använda koncentrationen av kopparacetat var 0,02 %, det tidigare bestämda MIC-värdet. Spädningar gjordes tills en slutkoncentration av 6,25 x 104 % uppnåddes. Klorhexi- dinkoncentrationen hölls konstant på 2,44 x 106 %, dvs 0,25 x MIC-värdet. Det bör påpekas att en signifikant inhibering av tillväxten (30 - 60%) erhölls med kombinationer av de två föreningarna vid koncentrationer som tillät tillväxt vid försök med endast en substans.In the first series of experiments, different concentrations of copper (II) acetate were mixed with chlorhexidine gluconate as shown in Fig. 1. The highest concentration of copper acetate used was 0.02%, the previously determined MIC value. Dilutions were made until a final concentration of 6.25 x 104% was reached. The chlorhexidine concentration was kept constant at 2.44 x 106%, ie 0.25 x the MIC value. It should be noted that a significant inhibition of growth (30 - 60%) was obtained with combinations of the two compounds at concentrations that allowed growth in experiments with only one substance.
Vid den andra serien av försök kunde en ändå mer uttalad ef- fekt iakttas då koppar(II)acetat i en koncentration av 0,125 x MIC-värdet blandades med klorhexidinglukonat i en koncentration varierande från MIC-värdet till 0,063 x MIC-värdet, så som visas i Fig. 2. Vid den lägsta undersökta koncentrationen, 0,125 x MIC-värdet för kopparacetat och 0,063 x MIC-värdet för klor- hexidínglukonat uppnåddes en inhibering av tillväxten på 30 - 40 %. Liknande resultat uppnåddes med A. viscosus isolat.In the second series of experiments, an even more pronounced effect could be observed when copper (II) acetate at a concentration of 0.125 x the MIC value was mixed with chlorhexidine gluconate at a concentration ranging from the MIC value to 0.063 x the MIC value, such as is shown in Fig. 2. At the lowest concentration examined, 0.125 x the MIC value for copper acetate and the 0.063 x MIC value for chlorhexidine gluconate, an inhibition of growth of 30-40% was achieved. Similar results were obtained with A. viscosus isolate.
Härav framgår således att en kombination av klorhexidin, och ett koppar(II)salt ger en synergistisk tillväxthämmande effekt på de undersökta bakteriestammarna.It thus appears that a combination of chlorhexidine and a copper (II) salt has a synergistic growth inhibitory effect on the bacterial strains examined.
Ett tandvårdsmedel enligt uppfinningen som omfattar en an- timikrobiell bisbiguanid i kombination med ett fysiologiskt god- tagbart kopparsalt uppvisar förutom en förbättrad plackinhibe- rande effekt vid lägre koncentration också en mindre grad av biverkningar i form av missfärgning av tänderna. En lösning kan lämpligen innehålla 0,5 - 5,5 mM bisbiguanid i kombination med 0,55 - 55 mM kopparsalt och en fast beredningsform lämpligen 2,1 - 21 mM bisbiguanid i kombination med 0,55 - 550 mM koppar- salt.A dentifrice according to the invention which comprises an antimicrobial bisbiguanide in combination with a physiologically acceptable copper salt exhibits not only an improved plaque inhibitory effect at lower concentration but also a minor degree of side effects in the form of discoloration of the teeth. A solution may suitably contain 0.5 - 5.5 mM bisbiguanide in combination with 0.55 - 55 mM copper salt and a solid dosage form suitably 2.1 - 21 mM bisbiguanide in combination with 0.55 - 550 mM copper salt.
Tandvårdsmedlet enligt uppfinningen kan föreligga i form av en sköljvätska, tandkräm eller gel samt även föreligga i en så- dan beredningsform som en tablett eller tuggummi. En sköljvätska kan innehålla 0,05 % - 0,5 viktprocent bisbiguanid som acetat eller glukonat och 0,01 - 1 % kopparacetat eller kopparglukonat.The dentifrice according to the invention may be in the form of a rinsing liquid, toothpaste or gel and may also be in a dosage form such as a tablet or chewing gum. A rinsing liquid may contain 0.05% to 0.5% by weight of bisbiguanide as acetate or gluconate and 0.01 to 1% of copper acetate or copper gluconate.
En tandkräm eller gel bör innehålla 0,2 - 2 viktprocent bisbi- guanid som acetat eller glukonat och 0,01 till 10 viktprocent kopparacetat eller kopparglukonat. En tablett eller tuggummi bör innehålla 0,2 - 2 viktprocent bisbiguanid som acetat eller glukonat och 0,01 till 10 viktprocent kopparacetat eller koppar- glukonat. (1A toothpaste or gel should contain 0.2 to 2% by weight of bisbiguanide as acetate or gluconate and 0.01 to 10% by weight of copper acetate or copper gluconate. A tablet or chewing gum should contain 0.2 to 2% by weight of bisbiguanide as acetate or gluconate and 0.01 to 10% by weight of copper acetate or copper gluconate. (1
Claims (6)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE8900915A SE465905B (en) | 1989-03-15 | 1989-03-15 | DENTALS CONTAINING AN ACETATE OR GLUCONATE SALT OF AN ANTIMICROBIAL BISBIGUANIDE |
| AU53515/90A AU5351590A (en) | 1989-03-15 | 1990-03-15 | Dental preparation |
| PCT/SE1990/000165 WO1990010434A1 (en) | 1989-03-15 | 1990-03-15 | Dental preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE8900915A SE465905B (en) | 1989-03-15 | 1989-03-15 | DENTALS CONTAINING AN ACETATE OR GLUCONATE SALT OF AN ANTIMICROBIAL BISBIGUANIDE |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| SE8900915D0 SE8900915D0 (en) | 1989-03-15 |
| SE8900915L SE8900915L (en) | 1990-09-16 |
| SE465905B true SE465905B (en) | 1991-11-18 |
Family
ID=20375350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8900915A SE465905B (en) | 1989-03-15 | 1989-03-15 | DENTALS CONTAINING AN ACETATE OR GLUCONATE SALT OF AN ANTIMICROBIAL BISBIGUANIDE |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU5351590A (en) |
| SE (1) | SE465905B (en) |
| WO (1) | WO1990010434A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19857151A1 (en) * | 1998-12-11 | 2000-06-15 | Degussa | Powdered, water-soluble chlorhexidine salt, useful e.g. as disinfectant in cosmetics, contains anion from specific sugar acids or their lactones |
| US20050191247A1 (en) * | 2004-03-01 | 2005-09-01 | David Drake | Chlorhexidine compositions |
| CZ308891B6 (en) | 2014-10-01 | 2021-08-11 | Wald Pharmaceuticals s.r.o | Application composition for increasing the effectiveness of antiseptics and / or disinfectants, application composition containing the application composition, and using this composition |
| CN113476386A (en) * | 2021-08-19 | 2021-10-08 | 杭州迅腾医疗器械有限公司 | Gargle and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU8342975A (en) * | 1974-08-09 | 1977-02-03 | Procter & Gamble | Oral compositions for plaque, caries and calculus retardationwith reduced staining tendencies |
| DE3065015D1 (en) * | 1980-04-29 | 1983-11-03 | Blendax Werke Schneider Co | Toothpaste |
| DE3532860C1 (en) * | 1985-09-14 | 1987-03-12 | Blendax Werke Schneider Co | Oral hygiene products |
| DE3600165A1 (en) * | 1986-01-07 | 1987-07-09 | Blendax Werke Schneider Co | AGENT FOR ORAL HYGIENE |
-
1989
- 1989-03-15 SE SE8900915A patent/SE465905B/en not_active IP Right Cessation
-
1990
- 1990-03-15 AU AU53515/90A patent/AU5351590A/en not_active Abandoned
- 1990-03-15 WO PCT/SE1990/000165 patent/WO1990010434A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO1990010434A1 (en) | 1990-09-20 |
| AU5351590A (en) | 1990-10-09 |
| SE8900915D0 (en) | 1989-03-15 |
| SE8900915L (en) | 1990-09-16 |
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