WO1987000005A1 - A COMPOSITION FOR DISINFECTION OF THE VAGINAL AND OTHER MUCOUS MEMBRANES WITH LOW pH - Google Patents

A COMPOSITION FOR DISINFECTION OF THE VAGINAL AND OTHER MUCOUS MEMBRANES WITH LOW pH Download PDF

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Publication number
WO1987000005A1
WO1987000005A1 PCT/SE1986/000310 SE8600310W WO8700005A1 WO 1987000005 A1 WO1987000005 A1 WO 1987000005A1 SE 8600310 W SE8600310 W SE 8600310W WO 8700005 A1 WO8700005 A1 WO 8700005A1
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WO
WIPO (PCT)
Prior art keywords
chlorhexidine
vaginal
tris
composition
salt
Prior art date
Application number
PCT/SE1986/000310
Other languages
French (fr)
Inventor
Karen Kvist Christensen
Poul Christensen
Tomas Laszlo
Original Assignee
Dermaci Ab
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Filing date
Publication date
Application filed by Dermaci Ab filed Critical Dermaci Ab
Publication of WO1987000005A1 publication Critical patent/WO1987000005A1/en
Priority to NO870839A priority Critical patent/NO870839L/en
Priority to DK105587A priority patent/DK105587A/en

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44—Guanidine; Derivatives thereof

Definitions

  • the present invention relates to compositions for disinfection of the vaginal and other mucous membra ⁇ nes with low pH and to the use of such compositions.
  • Chlorhexidine solutions are widely used for dis- infection of the vagina before operation and delivery. Nevertheless, the documentation concerning the use of chlorhexidine in the vagina is very scarce (1-6), in contrast to other applications of chlorhexidine.
  • Chlorhexidine was developed during the 1950ties and has since proved effective as a disinfection agent for skin and mucosas.
  • GBS are bacteria causing infections in mothers and infants in connection with pregnancy and delivery.
  • the killing kinetics for GBS depends on the chlor ⁇ hexidine concentration as well as on the time of contact between the agent and GBS. For example, 7 hours' ex- position was required at a concentration of 63 mg chlorhexidine/1 , whereas only one hour was required at 500 mg/1 (1) .
  • chlorhexidine is approxi ⁇ mately 100 times less effective at pH 5 compared to pH 7 (7).
  • the pH of the vagina of healthy non-pregnant women of fertile age is generally between 3 and 4. During pregnancy, the pH is somewhat higher (see below).
  • the buffering capacity of the chlorhexi- 5 dine solutions currently on the market is extremely low (7).
  • the present invention thus relates to a composi ⁇ tion for disinfection of the vaginal and other mucous membranes with low pH, which composition comprises a salt of chlorhexidine (N,N"-bis-(chlorophenyl)-3,12- -diimino-2,4,11,13-tetraazatetradecandiimidamid) and an ethoxylated alkyl phenol, which composition is buffered to a pH of at least 7.
  • Chlorhexidine is used at a salt, for instance acetate, hydrochloride or gluconate of chlorhexidine. Synonyms to chlorhexidine are:
  • N'-diguanido)-hexane 1,6-di(4'-chloro-phenyldiguanido)- hexan; (Hibitane; Nolvasan; Rotersept; Sterilon; Hibiscrub; Hibisol; Chlorhexamed; Corsodyl; Gibitan; Soretol; Chlorohex; Fi eil; Hexadol; Tubulicid; Disteryl; Abacil; Septeal).
  • composition according to the present invention is preferably buffered with a TRIS buffer.
  • TRIS buffer Synonyms to TRIS buffer are: Tromethamine (2-amino-2-hydroxymethyl-l,3-propanediol) ; trimethylol aminomethane; TRIS (hydroxymethyl) amino- methane; trisamine; aminotris (hydroxymethyl) methane; methanamine; aminotrimethylomethane; tris (hydroxy ⁇ methyl)methanamine; tris buffer; trometamol; Tromet ane; THAM; TRIS; Talatrol; Tham-E; Tris Amino; Tris-steril; Trizma; Pehanorm; Tutofusin tris; Addex-Tham; Trisa inol; Triladye) .
  • an ethoxy ⁇ lated alkyl phenol is incorporated.
  • An example of ethoxylated alkylphenols is nonoxynol-9 conforming to the formula
  • n is the number of ethylene oxid (EO) moities, varying from 5 to 18 with an average of 9.
  • Synonyms to nonoxynol-9 are: Ethylene glycol nonyl phenyl ether, Nonylphenoxypoly- ethoxyethanol, Nonylphenoxy polyethoxy ethanol, PEG nonyl phenyl ether, Polyethylene glycol nonyl phenyl ether, Poly (ethylene glycol) p-nonylphenyl ether, Polyoxyethylene nonylphenyl ether, Nonylphenyl poly- ethylene glycol ether, p-Nonylphenyl poly(oxyethylene)- ether, Nonylphenoxypoly(ethyleneoxy)ethanol, Nonyl- phenol ethoxylate.
  • the composition may be present as an aqueous solution or in form of a vaginal tablet, powder, cream or ointment.
  • the composition is an aqueous solution comprising 0.1-20 g/1 of the salt of chlor ⁇ hexidine, 1-40 g/1 of the ethoxylated alkyl phenol and which solution is buffered with 0.01-1 M TRIS buffer to a pH of at least 7.
  • the ion concentra ⁇ tion is equivalent to a solution of sodium chloride of not more than a 0.1%.
  • the concentration of the ingredients are: 0.1-20 g/kg of the salt of chlorhexi ⁇ dine, 1-40 g/kg of the ethoxylated alkyl phenol and 0.01 M TRIS buffer, respectively.
  • the invention also comprises a method of disin ⁇ fecting the vaginal or other mucous membranes by con- tacting said membranes with a composition comprising a salt of chlorhexidine and an ethoxylated alkyl phenol, which composition is buffered to a pH of at least 7.
  • a composition comprising a salt of chlorhexidine and an ethoxylated alkyl phenol, which composition is buffered to a pH of at least 7.
  • the accompanying drawing shows a diagram of the effect of addition of TRIS buffer to chlorhexidine on the killing of group B streptococci suspended in a solution of pH 5. COMPATIBILITY TESTS
  • the pH of the solutions was adjusted to 8.0 using 1 M acetic acid.
  • the chemical stability of chlorhexidine was tested by gas chromatographic analysis through extraction and derivation as described in reference no. 9. No chemical alteration of the chlorhexidine molecule was detected.
  • white sediments were noted in all solutions with nonoxynol-9 concentration lower than 5 g/1, thus proving that the presense of an ethoxylated alkyl phenol makes the composition more stable.
  • Chlorhexidine digluconate 10 g/1 or chlorhexidine diacetate 5 g/1, 2 g/1, 1 g/1 or 0.1 g/1 was mixed with TRIS buffer 1 M, 0.1 M, 0.05 M or 0.01 M.
  • Series of two-fold dilutions of each mixture were prepared in sterile distilled water.
  • One milliliter of each chlorhexidine preparation was then mixed with 1 ml of each of the above bacterial cultures.
  • At diffe ⁇ rent -intervals after mixing 2 ⁇ l of each suspension were streaked on a conventional blood agar plate, which was then incubated at 37°C for 48 hours. The plates were inspected for appearance of bacterial colonies.

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  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The composition comprises a salt of chlorhexidine and an ethoxylated alkyl phenol and is buffered to a pH of at least 7. A method of disinfecting the vaginal or other mucous membranes with the use of the composition is also described.

Description

A COMPOSITION FOR DISINFECTION OF THE VAGINAL AND OTHER MUCOUS MEMBRANES WITH LOW pH
The present invention relates to compositions for disinfection of the vaginal and other mucous membra¬ nes with low pH and to the use of such compositions.
Chlorhexidine solutions are widely used for dis- infection of the vagina before operation and delivery. Nevertheless, the documentation concerning the use of chlorhexidine in the vagina is very scarce (1-6), in contrast to other applications of chlorhexidine.
Chlorhexidine was developed during the 1950ties and has since proved effective as a disinfection agent for skin and mucosas. A study has been made regarding the possibility of suppressing group B streptococci (GBS) in the vagina by washing vaginally with chlorhexi¬ dine. GBS are bacteria causing infections in mothers and infants in connection with pregnancy and delivery. In in vitro experiments, it has been demonstrated that the killing kinetics for GBS depends on the chlor¬ hexidine concentration as well as on the time of contact between the agent and GBS. For example, 7 hours' ex- position was required at a concentration of 63 mg chlorhexidine/1 , whereas only one hour was required at 500 mg/1 (1) .
In in vivo experiments, it has been shown that at least 1 hour of contact between the mucosa and chlorhexidine was reguired to suppress the growth of GBS in the vagina (2). When chlorhexidine is used preoperatively or for example before insertion of an intrauterine device, the operation or application is started immediately after the chlorhexidine washing. It is therefore evident that chlorhexidine is without effect in these situations.
It has been shown that chlorhexidine is approxi¬ mately 100 times less effective at pH 5 compared to pH 7 (7). The pH of the vagina of healthy non-pregnant women of fertile age is generally between 3 and 4. During pregnancy, the pH is somewhat higher (see below). Furthermore, the buffering capacity of the chlorhexi- 5 dine solutions currently on the market is extremely low (7).
In order to investigate the effect of a non-buffered chlorhexidine solution on the vaginal pH, the pH of the vaginal ucosa of pregnant women was determined 10 before and after vaginal washing with chlorhexidine diacetate, 2 g/1, in connection with a clinical study in which the washing was performed as previously de¬ scribed (2). The results were
15 pH before washing: 5.30 - 6.10 (average 5.7) pH immediately after washing 5.70 - 6.30 (average 5.9) pH 30 min after washing 5.49 - 6-10 (average 5.7)
No statistically significant differences (Student's t-Test) were detected between the pH values before, immediately after, and 30 min after washing. It was concluded that the pH values did not change with the use of the currently available chlorhexidine solution.
^ 75 It should also be notified that the pH value in healthy, non-pregnant women of fertile age is even lower. The effect of chlorhexidine diacetate on the pH of the vagina in 10 such women was also studied. All pH values were below 5 immediately after washing.
30 Surprisingly, it has now been found that a mixture of chlorhexidine and a buffer will exhibit a superior capacity to suppress and eradicate microorganisms in the vagina when compared to currently available chlorhexidine solutions.
->5 The present invention thus relates to a composi¬ tion for disinfection of the vaginal and other mucous membranes with low pH, which composition comprises a salt of chlorhexidine (N,N"-bis-(chlorophenyl)-3,12- -diimino-2,4,11,13-tetraazatetradecandiimidamid) and an ethoxylated alkyl phenol, which composition is buffered to a pH of at least 7. Chlorhexidine is used at a salt, for instance acetate, hydrochloride or gluconate of chlorhexidine. Synonyms to chlorhexidine are:
( ,N"-Bis(4-chlorophenyl)-3 ,12-diimino-2,4,11,13-tetra- azatetradecandiimidamide; 1,1'-hexamethylenebis[5-(p- -chlorophenyl)biguanide]; l,6-bis-(N -p-chlorophenyl-
N'-diguanido)-hexane; 1,6-di(4'-chloro-phenyldiguanido)- hexan; (Hibitane; Nolvasan; Rotersept; Sterilon; Hibiscrub; Hibisol; Chlorhexamed; Corsodyl; Gibitan; Soretol; Chlorohex; Fi eil; Hexadol; Tubulicid; Disteryl; Abacil; Septeal).
The composition according to the present invention is preferably buffered with a TRIS buffer. Synonyms to TRIS buffer are: Tromethamine (2-amino-2-hydroxymethyl-l,3-propanediol) ; trimethylol aminomethane; TRIS (hydroxymethyl) amino- methane; trisamine; aminotris (hydroxymethyl) methane; methanamine; aminotrimethylomethane; tris (hydroxy¬ methyl)methanamine; tris buffer; trometamol; Tromet ane; THAM; TRIS; Talatrol; Tham-E; Tris Amino; Tris-steril; Trizma; Pehanorm; Tutofusin tris; Addex-Tham; Trisa inol; Triladye) .
In order to stabilise the composition, an ethoxy¬ lated alkyl phenol is incorporated. An example of ethoxylated alkylphenols is nonoxynol-9 conforming to the formula
CgH19(OCH2CH2)nOH
wherein n is the number of ethylene oxid (EO) moities, varying from 5 to 18 with an average of 9. Synonyms to nonoxynol-9 are: Ethylene glycol nonyl phenyl ether, Nonylphenoxypoly- ethoxyethanol, Nonylphenoxy polyethoxy ethanol, PEG nonyl phenyl ether, Polyethylene glycol nonyl phenyl ether, Poly (ethylene glycol) p-nonylphenyl ether, Polyoxyethylene nonylphenyl ether, Nonylphenyl poly- ethylene glycol ether, p-Nonylphenyl poly(oxyethylene)- ether, Nonylphenoxypoly(ethyleneoxy)ethanol, Nonyl- phenol ethoxylate.
All the above compounds are known per se.
The toxicologies of chlorhexidine, TRIS and the ethoxylated alkyl phenols (in particular nonoxynol-9) have been extensively reviewed, and the compounds are all well known as very little toxic.
The composition may be present as an aqueous solution or in form of a vaginal tablet, powder, cream or ointment. Preferably, the composition is an aqueous solution comprising 0.1-20 g/1 of the salt of chlor¬ hexidine, 1-40 g/1 of the ethoxylated alkyl phenol and which solution is buffered with 0.01-1 M TRIS buffer to a pH of at least 7. In another preferred embodiment the ion concentra¬ tion is equivalent to a solution of sodium chloride of not more than a 0.1%.
When the composition is in the form of a tablet, powder, cream or ointment, the concentration of the ingredients are: 0.1-20 g/kg of the salt of chlorhexi¬ dine, 1-40 g/kg of the ethoxylated alkyl phenol and 0.01 M TRIS buffer, respectively.
The invention also comprises a method of disin¬ fecting the vaginal or other mucous membranes by con- tacting said membranes with a composition comprising a salt of chlorhexidine and an ethoxylated alkyl phenol, which composition is buffered to a pH of at least 7. The accompanying drawing shows a diagram of the effect of addition of TRIS buffer to chlorhexidine on the killing of group B streptococci suspended in a solution of pH 5. COMPATIBILITY TESTS
The compatibility between a chlorhexidine salt and different buffers has been investigated. In a series of repeated experiments, chlorohexidine gluco- nate 10 g/1 and 1 g/1, as well as chlorhexidine acetate
2 g/1 and 0.1 g/1 were mixed with buffer substances in concentrations of 1, 0.1 or 0.01 M. The pH of the solutions was 7.5. After one hour at 22°C, the mixtures were inspected for sedimentation with the naked eye. Buffer Occurrence of a white sediment
Potassium phosphate yes
Sodium phosphate yes
Sodium borate yes
Sodium citrate yes Sodium carbonate yes
Sodium bicarbonate yes
Sodium lactate yes
TRIS ' no
As is evident, TRIS did not cause any formation of sediment together with a salt of chlorhexidine in this experiment.
In further compatibility experiments, mixtures of a chlorhexidine salt and TRIS in the above mentioned concentrations were placed alternatively at -15°C and +45°C for periods of 12 hours each. Already after one freezing period, a white sediment became visible to the naked eye. STABILITY TESTS In other experiments, a salt of chlorhexidine, TRIS buffer and ethoxylated alkyl phenol, represented by nonoxynol-9, were mixed, using the following con¬ centrations of the compounds:
A. Chlorhexidine digluconate 20 g/1 and 10 g/1 or chlorhexidine diacetate 5 g/1, 2 g/1, 1 g/1 and
0.1 g/1.
B. TRIS buffer 1 M, 0.1 M, 0.05 M and 0.01 M.
C. Nonoxynol-9 40 g/1, 20 g/1, 10 g/1, 5 g/1, 2 g/1 and 1 g/1. The pH of the solutions was adjusted to 8.0 using 1 M acetic acid. The chemical stability of chlorhexidine was tested by gas chromatographic analysis through extraction and derivation as described in reference no. 9. No chemical alteration of the chlorhexidine molecule was detected. In experiments with alternating temperatures as described above, white sediments were noted in all solutions with nonoxynol-9 concentration lower than 5 g/1, thus proving that the presense of an ethoxylated alkyl phenol makes the composition more stable. ANTI-MICROBIAL TEST
The anti-microbial effect of mixtures of a salt of chlorhexidine and TRIS was studied in vitro. Cultures of 10 different bacterial strains of Staphylococcus aureus, 10 different Escherichia coli and 10 GBS, all of which strains had been isolated from the vagina of women, were prepared by inoculating the strains - for 18 hours at 37°C on Todd Hewitt broth. The pH was then adjusted to 5.0 in all broths, using 1 M acetic acid.
Chlorhexidine digluconate 10 g/1 or chlorhexidine diacetate 5 g/1, 2 g/1, 1 g/1 or 0.1 g/1 was mixed with TRIS buffer 1 M, 0.1 M, 0.05 M or 0.01 M. Series of two-fold dilutions of each mixture were prepared in sterile distilled water. One milliliter of each chlorhexidine preparation was then mixed with 1 ml of each of the above bacterial cultures. At diffe¬ rent -intervals after mixing, 2 μl of each suspension were streaked on a conventional blood agar plate, which was then incubated at 37°C for 48 hours. The plates were inspected for appearance of bacterial colonies.
In all cases, the solutions containing TRIS buffer could be diluted more than the solutions containing the same concentrations of the salt of chlorhexidine alone and still kill the bacteria more rapidly. The figure shows one such example with a GBS strain. The original concentration of chlorhexidine digluconate was 10 g/1 in this experiment with an addition of 0.01 M TRIS. At the dilutions corresponding to chlor- hexidine concentrations 0.5 g/1 - 15 mg/1, a much more rapid killing was obtained in the presence of TRIS. It can also be deduced from the figure that the socalled minimal bactericidal concentration of chlorhexidine dropped from 0.125 g/1 to 0.031 g/1 in this example. EXAMPLE 1
5 g chlorhexidine diacetate and 9.1 g TRIS were mixed in 850 ml distilled water during stirring. 31.25 g of 64% nonoxynol-9 was then added, followed by further stirring, resulting in a clear solution. The pH was adjusted to 8.0 using 1 M acetic acid (appoximately 53 ml). The total volume was increased to 1000 ml with distilled water. EXAMPLE 2 A solution of similar concentrations as in Example 1 of chlorhexidine diacetate and TRIS at pH 8.0 was prepared in distilled water but without nonoxynol-9. Living suspensions of the bacterial strains described above were prepared. Furthermore, a pair of correspon- ding solutions containing 2 g chlorhexidine diacetate/1 instead of 5 g/1 were made.
Mixtures of test solutions and bacteria were prepared and subcultures made after various contact times. An example of the effect of nonoxynol-9 with a group B streptococcal strain is shown in the following Table, but similar results were obtained with the other bacteria. Thus, nonoxynol-9 did not reduce the effect of chlorhexidine diacetate. In contrast, a slight but significant increase in anti-bacterial effect was detected when nonoxynol-9 was present. Table . Killing cinetics for a group B streptococcal strain of, mixtures of chlorhexidine-, di¬ acetate, TRIS and nonoxynol-9 as compared to mixtures of chlorhexidine diacetate and TRIS alone
Disinfecting pre¬ Time after mixing Effect of dilution of the preparations tested paration tested bacteria and disin¬ (volume preparation: volume bacteria) fectant
5:1 1:1 0.25:1 0.06:1
A
(5g chlorhexidine +
TRIS + nonoxynol-9) immediately after ( +) 0 0 0
B
(5g chlorhexidine +
TRIS 0 0 0 0
A 30 min 0 0 0 B (+) 0 0 0 A 60 min + 0 0 B (+) 0 0 A 2 hours 0 0 B 0 0 A 3 hours (+) 0 B (+) 0 A 4 hours (+) 0 B (+) 0
Table (cont. ) .
C
(2g chlorhexidine +
TRIS + nonoxynol-9) immediately after
0 o o 0
D
(2g chlorhexidine +
TRIS) 0 0 0 0
C 30 min 0 0 0
D
(+) 0 0 0
C 60 min
(+) 0 0
D
0 0 0
C 2 hours
0 0
D
(+) 0 0
C 3 hours
0 0
D
(+) 0 0
C 4 hours
0
D
0
0 = no effect
(+) = impaired growth of bacteria
+ - no growth of bacteria
Using the three compounds, it is possible to design isotonic solutions. The above-mentioned mixture of 5 mg/ml of 0.05 M TRIS, 20 g/1 of nonoxynol-9 and 20-30 ml acetic acid to 1 litre distilled water is an example of such an isotonic solution.
References
1. Christensen KK, Christensen P, Dykes A-K, Kahlmeter G, Kurl DN & Linden V : Chlorhexidine for prevention of neonatal colonization with group B streptococci. I.
In vitro effect of chlorhexidine on group B streptococ¬ ci. Europ J Obstet Gynec reprod Biol. 16:157-165, 1983.
2. Dykes A-K, Christensen KK, Christensen P & Kahlmeter G : Chlorhexidine for prevention of neonatal colonization with group B streptococci. II. Chlorhexidine concentra¬ tions and recovery of group B streptococci following vaginal washing in pregnant women. Europ J Obstet Gynec reprod Biol. 16:167-172, 1983.
3. Christensen KK, Christensen P, Dykes A-K & Kahlmeter G : Chlorhexidine for prevention of neonatal colonization with group B streptococci. III. Effect of vaginal washing with chlorhexidine before rupture of the membranes. Europ J Obstet Gynec- reprod Biol. 19:231-236, 1985.
4. Christensen KK, Dykes A-K & Christensen P : Reduced colo¬ nization of newborns with group B streptococci following vaginal washing of the birth canal with chlorhexidine.
J Perinat Med. 13:239-243, 1985.
5. Vorherr H, Vorherr UF, Mehta P, Ulrich JA & Messer RH : Antimicrobial effect of chlorhexidine and povidoneiodine on vaginal bacteria. Journal of Infection 8:195-199, 1984.
6. Christensen KK & Christensen P : Chlorhexidine for pre¬ vention of neonatal colonization with GBS. In: Christen¬ sen KK, Christensen P & Ferrieri P : Neonatal group B streptococcal infections. Antibiot Chemother. 35:296- 302, Karger, Basel 1985. 7. Hellstrδm H, Cardell B, Loven G, Nilehn B & Persson A-L : Antimikrobiell effekt av klorhexidin i olika preparationsformer. Lakarsallskapets riksstamma, 28- 30 Nov. 1984 (8P).

Claims

1. A composition for disinfection of the vaginal and other mucous membranes with low pH, c h a r a c ¬ t e r i z e d in that it comprises a salt of chlorhexi¬ dine (N,N"-bis(4-chlorophenyl)3,12-diimino-2,4,11,13- -tetraazatetradecandiimidamid) and an ethoxylated alkyl phenol and in that it is buffered to a pH of at least 7.
2. A composition according to claim 1, c h a ¬ r a c t e r i z e d in that it is an aqueous solution, which comprises 0.1-20 g/1 of the salt of chlorhexi¬ dine, 1-40 g/1 of the ethoxylated alkyl phenol and which is buffered with 0.01-1 M TRIS buffer (tris(hydroxy¬ methyl)aminomethane.
3. A composition according to claim 2, c h a r a c - t e r i z e d in that it has an ion concentration which is equivalent to a solution of sodium chloride of not more than 0.1% by weight.
4. A composition according to claim 1, c a r a c ¬ t e r i z e d in that it is in the form of a vaginal tablet, powder, cream or ointment.
5. A composition according to any one of claims 1-4, c h a r a c t e r i z e d in that the salt of chlorhexidine is chlorhexidine gluconate, chlorhexi¬ dine hydrochloride or chlorhexidine diacetate.
6. A method of disinfecting the vaginal or other mucous membranes with low pH, said method comprising contacting said membranes with a composition, which comprises a salt of chlorhexidine (N,N"-bis(4-chloro- phenyl)-3,12-diamino-2,4,11,13-tetraazatetradecandi- imidamid) and an ethoxylated alkyl phenol, and which is buffered to a pH of at least 7.
PCT/SE1986/000310 1985-07-01 1986-06-26 A COMPOSITION FOR DISINFECTION OF THE VAGINAL AND OTHER MUCOUS MEMBRANES WITH LOW pH WO1987000005A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
NO870839A NO870839L (en) 1985-07-01 1987-02-27 MATERIAL FOR DISINFINING THE VAGINA MASK AND OTHER LOW PH.
DK105587A DK105587A (en) 1985-07-01 1987-02-27 MEDICINE FOR DISINFECTION OF VAGINAL AND OTHER LOW PH MASTERS

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8503256A SE8503256L (en) 1985-07-01 1985-07-01 MIXTURE OF CHLOREXIDE AND TRIS BUFFER FOR USE IN THE VAGINA, SKIN AND OTHER MUSCLES WITH ADDED PH
SE8503256-3 1985-07-01

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Publication Number Publication Date
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EP0356264A2 (en) * 1988-08-22 1990-02-28 Becton, Dickinson and Company Cleansing composition for topical disinfection
DE4005784A1 (en) * 1990-02-23 1991-08-29 Schuelke & Mayr Gmbh Disinfectant concentrates effective against mycobacteria and viruses - contg. phenoxy-ethanol or -propanol, guanidinium or quat. ammonium cpd., nonionic surfactant, and N-base as synergist
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EP0631472A1 (en) * 1992-03-18 1995-01-04 The Trustees of Columbia University in the City of New York Antiviral contraceptive devices, particularly condoms
GR1003598B (en) * 2000-07-05 2001-06-14 Santa Ν.Μπαλανος Αβεε Technical description of an "oral solution of chlorhexidine and phenoxyethanol in the correct proportions so as to ensure synergistic antimicrobial action

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GB8630823D0 (en) * 1986-01-16 1987-02-04 Ici Plc Antiseptic compositions

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Cited By (9)

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Publication number Priority date Publication date Assignee Title
GB2191942B (en) * 1985-09-23 1989-12-06 Affiliated Innovat Manag Inc Vaginal conditioning for sexual activity
EP0356264A2 (en) * 1988-08-22 1990-02-28 Becton, Dickinson and Company Cleansing composition for topical disinfection
EP0356264A3 (en) * 1988-08-22 1991-03-06 Becton, Dickinson and Company Cleansing composition for topical disinfection
DE4005784A1 (en) * 1990-02-23 1991-08-29 Schuelke & Mayr Gmbh Disinfectant concentrates effective against mycobacteria and viruses - contg. phenoxy-ethanol or -propanol, guanidinium or quat. ammonium cpd., nonionic surfactant, and N-base as synergist
EP0555116A2 (en) * 1992-01-22 1993-08-11 Hutchinson Compositions based on antiseptics and their applications
EP0555116B1 (en) * 1992-01-22 1999-04-14 Hutchinson Compositions based on antiseptics and their applications
EP0631472A1 (en) * 1992-03-18 1995-01-04 The Trustees of Columbia University in the City of New York Antiviral contraceptive devices, particularly condoms
EP0631472A4 (en) * 1992-03-18 1995-06-21 Univ Columbia Antiviral contraceptive devices, particularly condoms.
GR1003598B (en) * 2000-07-05 2001-06-14 Santa Ν.Μπαλανος Αβεε Technical description of an "oral solution of chlorhexidine and phenoxyethanol in the correct proportions so as to ensure synergistic antimicrobial action

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SE8503256L (en) 1987-01-02
DK105587D0 (en) 1987-02-27
AU6126886A (en) 1987-01-30
SE8503256D0 (en) 1985-07-01

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