CA2104462A1 - Oral and personal hygiene articles containing active agents bonded to the surface thereof - Google Patents
Oral and personal hygiene articles containing active agents bonded to the surface thereofInfo
- Publication number
- CA2104462A1 CA2104462A1 CA002104462A CA2104462A CA2104462A1 CA 2104462 A1 CA2104462 A1 CA 2104462A1 CA 002104462 A CA002104462 A CA 002104462A CA 2104462 A CA2104462 A CA 2104462A CA 2104462 A1 CA2104462 A1 CA 2104462A1
- Authority
- CA
- Canada
- Prior art keywords
- article
- active agent
- polymeric material
- group
- propyl
- 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
Links
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
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/34—Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
-
- 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
- A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
Abstract
2104462 9215198 PCTABS00016 An article suitable for oral or personal hygiene use, such as a toothbrush, toothpick, dental floss, denture, razor, eye glasses, contact lens, hair brush or comb, and comprised of polymeric material, has one or more chemically or biologically active agent(s) bonded to the surface thereof.
Description
W O 92/15198 21~ 4 ~ 6 2 PC~r/~S91/09116 ORAL & PERSONAL HYGIENE ARTICLES
CONTAINING ACTIVE AGENTS
BONDED TO THE SURFACE THEREOF
SUMMARY OF T~E I~ENTION
This invention relates to articles suitable for oral and personal hygiene use and comprised of polymeric material wherein the articles have bonded to the surface thereof one or more chemically or biologically active agent(s). Some examples of suitable articles include eye glasses, contact lens, toothbrushes, tooth picks, dentures, dental floss, razors, hair brushes and combs.
The polymeric material is selected from the group 15 consisting of polyamides, polystyrenes, styrene-acrylonitrile copolymers, acrylonitrile-butadiene-styrene copolymers, polyacrylates, polyesters and polypropylenes;
preferably nylon and cellulose acetate propionate. The active agent preferably is a quaternary ammonium 20 compound, such as 3-(trimethoxysilyl) propyldimethyloctadecyl ammonium chloride.
This invention also relates to a method for applying a coating of chemically or biologically active agent(s) to an oral or personal hygiene article comprised of 25 polymeric material by (a) directly permanently bonding said active agent to the surface of said article, or (b) tl) contacting said articles with an acid, alkaline hydroxide or organic solvent and (2) subsequently permanently bonding said active agent(s) to the surface 30 of sàid article.
The invention yields oral and personal hygiene articles which have anti-bacterial and/or anti-microbial coatings and/or coatings of active agents useful in retarding or preventing plague, gingivitis, 3-periodontitis, tooth and gum pain and diseases and infections of the skin, hair, scalp and eyes.
.. - :- - : : . :: . - ,: ., ,. . , ' ' : : :. ' ' ' :: : -' ~ ' ' ':: :' .
2l ~ 62 - 2 -BACKGROUND OF THE INVENTION AND INFORMATION DISCLOSUR' Oral and personal hygiene articles, such as toothbrushes and dental floss and the like, are constantly being improved for more effective cleaning and other benefits. Some of the benefits include the delivery of active agents to the teeth and gums and disinfectant properties of the oral hygiene articles.
8ecause toothbrushes, hair brushes and combs, in particular, can be a haven for bacterial and/or microbial growth, it would be especially beneficial to provide a toothbrush or other oral and personal hygiene articles which inhibit or prevent the growth of bacteria and/or other microbes thereon. Thus, it is an object of this invention to provide oral and personal hygiene articles 15 which have one or more active agents bonded to the surface thereof. It is a further object of this invention to provide oral and personal hygiene articles which possess permanent or long-lasting anti-bacterial and/or anti-microbial activity. It is another object of 20 this invention to provide an easy and efficient method for applying a coating of active agent(s) to an oral or personal hygiene article by (a) directly permanently bonding the active agent(s) to the surface of the article or (b) by contacting it with an acid, alkaline base or 25 organic solvent and subsequently permanently bonding the active agent(s) to the surface of the article.
Many references in the art describe antibacterial compositions and the use of these to treat various surfaces. US Patent No. 4,866,192 describes 30 organosilicone quaternary ammonium antimicrobial compounds to treat rayon fabric and other surfaces. US
Patent No. 4,371,577 describes antimicrobial carpet which has been treated with an amino acid type surfactant and an organosilicone quaternary ammonium salt. US Patent 35 No. 4,621,120 describes antibacterial compositions comprising vinyl copolymers having quaternary nitrogen groups. These compositions are disclosed as being useful in mouthwashes, toothpastes and dental creams.
US Patent No. 3,170,90l describes quaternary ammonium compounds and polymers thereof which are useful in treating paper and textile fabrics for imparting ,, ~ - . . .: . : -, --~ ~'- -. ' ':
- , . ~
.. ' ' ' , ' ~ 3 -2l ~q62 WO92/15198 PCT~US91/09116 - increase wet strength, water repellency, and resistance to shrinkage. US Patent No. 4,025,617 describes antimicrobial quaternary--ammonium copolymers formed by the condensation of at least two di-functional tertiary amines and 1,4-dihalo-2-butene. These copolymers are i described as being useful for the antimicrobial treatment of circulatory and standing waters.
US Patent No. 4,482,680 discloses poly(vinylbenzyl quaternary ammonium) halides which are useful as preservatives for cosmetic and pharmaceutical compositions and as disinfectant cleansers. US Patent No. 4,161,518 describes dentifrice compositions containing a quaternary ammonium organosilicone. US
Patent No. 4,394,378 describes certain silyl quaternary ammonium salts, such as 3-(trimethoxylsilyl) propyldidecylmethyl ammonium chloride, which is useful for antimicrobial treatment of textile fibers, siliceous-materials, rnetals, leather, wood and plastics.
US Patent No. 4,161,518 describes dentifrice 20 compositiOns containing a quaternary ammonium organosiloxane which is useful in inhibiting plaque formation on teeth. US Patent No. 4,615,937 describes antimicrobially-active web and wet wipes containing an organosilicone quaternary ammonium salt. US Patent No.
CONTAINING ACTIVE AGENTS
BONDED TO THE SURFACE THEREOF
SUMMARY OF T~E I~ENTION
This invention relates to articles suitable for oral and personal hygiene use and comprised of polymeric material wherein the articles have bonded to the surface thereof one or more chemically or biologically active agent(s). Some examples of suitable articles include eye glasses, contact lens, toothbrushes, tooth picks, dentures, dental floss, razors, hair brushes and combs.
The polymeric material is selected from the group 15 consisting of polyamides, polystyrenes, styrene-acrylonitrile copolymers, acrylonitrile-butadiene-styrene copolymers, polyacrylates, polyesters and polypropylenes;
preferably nylon and cellulose acetate propionate. The active agent preferably is a quaternary ammonium 20 compound, such as 3-(trimethoxysilyl) propyldimethyloctadecyl ammonium chloride.
This invention also relates to a method for applying a coating of chemically or biologically active agent(s) to an oral or personal hygiene article comprised of 25 polymeric material by (a) directly permanently bonding said active agent to the surface of said article, or (b) tl) contacting said articles with an acid, alkaline hydroxide or organic solvent and (2) subsequently permanently bonding said active agent(s) to the surface 30 of sàid article.
The invention yields oral and personal hygiene articles which have anti-bacterial and/or anti-microbial coatings and/or coatings of active agents useful in retarding or preventing plague, gingivitis, 3-periodontitis, tooth and gum pain and diseases and infections of the skin, hair, scalp and eyes.
.. - :- - : : . :: . - ,: ., ,. . , ' ' : : :. ' ' ' :: : -' ~ ' ' ':: :' .
2l ~ 62 - 2 -BACKGROUND OF THE INVENTION AND INFORMATION DISCLOSUR' Oral and personal hygiene articles, such as toothbrushes and dental floss and the like, are constantly being improved for more effective cleaning and other benefits. Some of the benefits include the delivery of active agents to the teeth and gums and disinfectant properties of the oral hygiene articles.
8ecause toothbrushes, hair brushes and combs, in particular, can be a haven for bacterial and/or microbial growth, it would be especially beneficial to provide a toothbrush or other oral and personal hygiene articles which inhibit or prevent the growth of bacteria and/or other microbes thereon. Thus, it is an object of this invention to provide oral and personal hygiene articles 15 which have one or more active agents bonded to the surface thereof. It is a further object of this invention to provide oral and personal hygiene articles which possess permanent or long-lasting anti-bacterial and/or anti-microbial activity. It is another object of 20 this invention to provide an easy and efficient method for applying a coating of active agent(s) to an oral or personal hygiene article by (a) directly permanently bonding the active agent(s) to the surface of the article or (b) by contacting it with an acid, alkaline base or 25 organic solvent and subsequently permanently bonding the active agent(s) to the surface of the article.
Many references in the art describe antibacterial compositions and the use of these to treat various surfaces. US Patent No. 4,866,192 describes 30 organosilicone quaternary ammonium antimicrobial compounds to treat rayon fabric and other surfaces. US
Patent No. 4,371,577 describes antimicrobial carpet which has been treated with an amino acid type surfactant and an organosilicone quaternary ammonium salt. US Patent 35 No. 4,621,120 describes antibacterial compositions comprising vinyl copolymers having quaternary nitrogen groups. These compositions are disclosed as being useful in mouthwashes, toothpastes and dental creams.
US Patent No. 3,170,90l describes quaternary ammonium compounds and polymers thereof which are useful in treating paper and textile fabrics for imparting ,, ~ - . . .: . : -, --~ ~'- -. ' ':
- , . ~
.. ' ' ' , ' ~ 3 -2l ~q62 WO92/15198 PCT~US91/09116 - increase wet strength, water repellency, and resistance to shrinkage. US Patent No. 4,025,617 describes antimicrobial quaternary--ammonium copolymers formed by the condensation of at least two di-functional tertiary amines and 1,4-dihalo-2-butene. These copolymers are i described as being useful for the antimicrobial treatment of circulatory and standing waters.
US Patent No. 4,482,680 discloses poly(vinylbenzyl quaternary ammonium) halides which are useful as preservatives for cosmetic and pharmaceutical compositions and as disinfectant cleansers. US Patent No. 4,161,518 describes dentifrice compositions containing a quaternary ammonium organosilicone. US
Patent No. 4,394,378 describes certain silyl quaternary ammonium salts, such as 3-(trimethoxylsilyl) propyldidecylmethyl ammonium chloride, which is useful for antimicrobial treatment of textile fibers, siliceous-materials, rnetals, leather, wood and plastics.
US Patent No. 4,161,518 describes dentifrice 20 compositiOns containing a quaternary ammonium organosiloxane which is useful in inhibiting plaque formation on teeth. US Patent No. 4,615,937 describes antimicrobially-active web and wet wipes containing an organosilicone quaternary ammonium salt. US Patent No.
2~ 4,721,511 describes antimicrobial fabrics having a bioactive amount of a silicone quaternary amine. US
Patent No. 4,282,366 describes natural and synthetic fabrics impregnated with organosilicone quaternary ammonium compounds as antimicrobial agents.
A method for preparing antimicrobial foams containing guaternary ammonium salts of silanes is described in US Patent No. 4,631,297. US Patent No.
4,408,996 describes a process for dying bioactive cellulosic fabrics by applying a mixture of
Patent No. 4,282,366 describes natural and synthetic fabrics impregnated with organosilicone quaternary ammonium compounds as antimicrobial agents.
A method for preparing antimicrobial foams containing guaternary ammonium salts of silanes is described in US Patent No. 4,631,297. US Patent No.
4,408,996 describes a process for dying bioactive cellulosic fabrics by applying a mixture of
3~ organosilicone polymer, a dye and a silyl quaternary amine.
US Patent No. 3,730,701 describes a method for controlling the growth of algae in water by adding certain silyl quaternary amines. US Patent No. 4,847,088 describes synergistic antimicrobial compositions comprising a quaternary ammonium compound and an acid : .. . .. . . :
.. . : . , :
. - . - . : ' . , :' , . :
.. . : : . . . . . .
.
WO92/15198 ~0 4 ~ 6 2 PCT/US91/09116 which are useful in treating carpets, fabrics, walls and furnishings.
Articles, such as "Disinfection of Water with Quaternary Ammonium Salts Insolubilized on a Porous Glass Surface," Nakagawa et al, A~plied and Environmental Microbioloay, March 1984, p-513-518; and "Algicidal Activity of a Surface-Bonded Organosilicone Quaternary Ammonium Chloride," Walters et al, AP~lied MicrobioloqY, Feb. 1973, P. 253~256 describe the antimicrobial activity ~0 of bound quaternary ammonium salts.
' :, , - : ~ , ~1 ~Lll~ 6 2 WO92/15198 PCT/US91/09]16 DETAILED DESCRI_TION
The present invention relates to personal and oral hygiene products which have been treated to bond active agent(s)to their surfaces. Specifically, the present invention involves an article comprised of polymeric material having bonded to the surface thereof one or more chemically or biologically active agent(s), wherein said article is suitable for oral or personal hygiene use, and said active agent is substantially l0 non-leachable from the surface of said article in a water-based medium.
Articles covered by this invention include any article of manufacture which is suitable for oral or personal hygiene use. Oral hygiene as used herein means useful for cleaning and caring for the teeth, gums, dentures or any other parts of the oral cavity. Personal hygiene as used herein means useful for cleaning and caring for the hair, scalp, skin, ears, nose, eyes and other parts of the face and head. Preferred articles 20 within the scope of this invention include a toothbrush, dental floss, toothpick, comb, hair brush, razor, eyeglass lens and frames and contact lens.
Suitable articles according to this invention may be composed partly or entirely of a polymeric material or 2~ have an exterior surface comprised of a polymeric material. The polymeric material can be a natural or synthetic polymer. The polymeric material preferably is polyamides, polyacrylates, polyesters, polypropylenes, polystyrenes, styrene-acryl-onitrile copolymers, acrylonitrile-butadien-estyrene copolymers, cellulose esters and blends andcombinations thereof. The most preferred polymeric materials are nylon and cellulose acetate propionate.
3- An essential feature of this invention is that the article has permanently bonded to the polymeric surface thereof one or more chemically or biologically active agent(s). These active agent(s) are bonded to the polymeric surfaces of the article, such that the agent(s) are substantially non-leachable from the surface of said article in a water-based medium. Suitable active agents : :. ' . . .: .
,. . .
: . ~ -. : . . . ~ .
,, :,,;~ : ~ ' . ., :
' ! ' .
21i0~46~ - 6 -W092/1~198 PCT/US91/091]6 would include any compound(s) having antimicrobial activity and which are capable of being bonded to the polymeric surfaces of the article. Preferred active agents include the quaternary ammonium compounds, ; organosilicone quaternary ammonium compounds, cetyl pyridinium compounds, guanidine compounds, bis-guanidine compounds and isothiouronium halide compounds.
Preferred quaternary ammonium compounds useful for this invention have the formula:
~ r 1 1 ~
R3 - N+ - R4-Y X
Wherein Rl is CH2-phenyl or an alkyl group containing about 8-22 carbon atoms; R2 is methyl, ethyl or an alkyl group containing about 8-22 carbon atoms; R3 is methyl or ethyl; R4 is an alkyl group containing about 1-6 carbon atoms; X is an anion; and Y is a group having the structure:
-Z, -OH, -OR5, -OC(O)R6, -CN, O O O
D D
25O-S-OQ, -C-O-R7 -C_CH, -S-R8, -S-Rg, O
-S-Rl -N-Rll ~ ANl;s -CH=CH2, 5~ R6~ R7~ R5~ Rg, Rlo, Rll, R12, are alkyl groups containing about 1-12 carbon atoms or phenyl; Z is halogen and Q is hydrogen or a cation.
3~
.
- ~ ~
s W092/15198 2 1 ~ `~ 4 6 ~ PCT/US91/09116 The more preferred organosilicone quaternary ammonium compounds useful for this invention have the formula:
CH30)3 Si(CH2)n I R3 ~
wherein Rl, R2, and ~3 are as described above, X is an anion and n is an integer from about 1-6 (preferably 3-6).
The most preferred organosilicone quaternary .;
15 ammonium compounds are n-octadecyldimethyl[3-(trimethoxysilyl)propyl] ammonium chloride, n-tetradecyldimethyl [3-(trimethoxysilyl) propyl] ammonium chloride, n-decyldimethyl[3-(trimethoxy-silyl)propyl] ammonium chloride, n-didodecylmethyl[3-(tri-methoxysilyl)propyll ammonium chloride, and n-dodecyldi-2~ methyl¦3-(trimethoxysilyl)propyl] ammonium chloride. . :
Other active agents can include the nitrogen as part ~-of a heterocyclic system, such as a cetyl pyridinium compound. The preferred.cetyl pyridinium compound is 30 2-(3-trimethoxy-æilylpropyl)-N-cetyl pyridinium bromide.
The isothiouronium halide compounds are also suitable for use as active agents according to this invention. The preferred isothiouronium halide compound for u~e in this invention is (trimethoxysilylpropyl) isothiouronium chloride.
The articles of this invention have the active agent(s) bonded to the polymeric surfaces of the ... . , . , : , , :: .
- ~ . : :, . :
,, : .. : :
W092/15198 ~10 4 4 6 2 PCT/US91/09116 articles, such that the active agent(s) is permanently attached to the articles. To be suitable for oral and personal hygiene use, the articles must have the active agent(s) bonded to the polymeric surfaces thereof such that the agent(s) is substantially non-leachable in an aqueous medium. Thus, the articles have a polymeric surface which has permanent antibacterial and/or antimicrobial activity which can not be leached out by saliva, shampoos, shaving creams, toothpastes and other aqueous-containing mediums.
The active agents can be permanently attached to the polymeric surfaces of the articles by any suitable means, ~uch as chemical linking using multifunctional reactive -organics (such as bis-carbenes or bis-nitrenes), silane coupling systems, plasma activation, flame activation, chemical treatment and other polymer grafting techniques.
The preferred attachment mechanism is a silane coupling system. It is believed, although Applicant does 2~ not intend to be limited thereby, that the alkoxysilyl end of the active agent is hydrolyzed to the corresponding hydroxy component in the presence of water.
This component then reacts with the active -OH, amide or 30 other reactive sites on the polymeric material. Although the active agent can be bonded to the polymeric surface of the article by any type of bonding, it is preferred that the agent be covalently bonded to the polymeric surface of the article.
The present invention also includes a method for applying a coating of chemically or biologically active agent to an oral or personal hygiene article comprised of polymeric material. This method can involve permanently , :", .
W092~15198 ~ 4 6 2 PCT/US91/09116 bonding the active agent directly to the untreated surface of the article. The method can also comprise the steps of:
l. contacting said article with a solvent selected from the group consisting of an aqueous-based organic or inorganic acid, an aqueous-based alkaline hydroxide or an organic solvent, and 2. subsequently bonding said active agent to the surface of said article.
The invention also includes articles which have been treated by the above ~ethods.
l~ It iQ believed, although Applicant does not intend to be bound or limited hereby, that treating the polymeric surface sf the article with the solvent exposes or forms reactive sites on the polymeric surface to which the active agents can bond. Preferably, the polymeric surface of the article has greater than about 2% of the surface area containing active sites for bonding of the 2~ active agent; more preferably greater than about 5%.
Thus, suitable solvents for treating the polymeric surfaces of the article include any material which would expose or form reactive -OH, amide, or other reactive 30 sites on the polymeric surfaces for bonding of the active agents. Some examples of suitable solvents include aqueous-based organic and inorganic acids, aqueous-based alkaline hydroxides and organic solvents. The preferred acids are sulfuric and acetic acid. The preferred alkaline hydroxides are potassium hydroxide and sodium hydroxide. Preferred organic solvents include methanol, ethanol, isopropanol, acetone and ethyl acetate.
" " ~', ~
:' ' ` ', . . ' ' ' ' ' .' ~ ', ' " ;' ' ' " ' ' . ' ~ , : ' WO 92/15198 ~ 4 ~ 2 PCI`/US91/09116 The polymeric surfaces of the articles are contacte~
with the solvent for a sufficient time ranging anywhere from a few minutes to several hours. The solvents can be u~ed alone, in combination or sequentially.
In bonding the active agent to the polymeric surface of the article, the article can be contacted with the active agent for a sufficient time for the active agent 10 to bond to the surface. Preferably, the active agent is in a solution of water or other suitable solvent. The solution can contain the active agent in any concentration, but preferably contains from about 1% to about 4% wt./vol. of the active agent. After contacting the article with the solution of active agent for a sufficient period of time (preferably about 30 minutes or longer), the article can be dried, rinsed and c~red at an elevated temperature (preferably about 50-125C). The drying and curing conditions,such as temperature, time and humidity, should be selected such that the 2S dimensional stability of the article is not adversely affected.
The articles of this invention are effective against a wide variety of microbial species, and they 30 continuously inhibit the growth of microbial organi~ms on the surface thereof. The articles have demonstrated antimicrobial activity against Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Streptococcus mutans/faecalis and Klebsiella pneumoniae.
The following examples are presented to help demonstrate the present invention. The examples are intended to be illustrative and not in a limitative ,.
WO92/15198 ~ 4 4 6 ~
sense. This invention includes the embodiments described and exemplified herein and all equivalents thereof. All parts and percentages used in the examples are on a weight basis unless otherwise indicated.
~0 ~0 , . :~ . . ~ ,: ~ :, WO92/15198 2 1 ~ 6 2 PCT/US91/09116 EXAMPLE I
Various treatment solutions were prepared within the scope of this invention containing 1%, 2% and 4%
wt./vol., respectively, of the active agent. Each solution was prepared by mixing lO ml. of concentrated acetic acid and 2 grams of surfactant (Zonyl FSN from DuPont Co.) with deionized water, followed by either lO, 20 or 40 grams of the active agent, to make one liter of each solution. The solution is agitated for about 30 minute~ to hydrolyze the active agent.
These solutions are presented in Table I below:
~ .
TABLE I
Solution Active Aqent Amt. (Wt.~Vol.) Sample l n-octadecyldimethyl 13-(trimethoxy-silyl)propyl] ammonium chloride 1%
20 Sample 2 " 2%
Sample 3 " 4%
Sample 4 n-tetradecyldimethyl ]3-trimethoxy-silyl)propyl] ammonium chloride 1%
2~ Sample 5 " 2%
Sample 6 " 4%
Sample 7(trimethoxysilylpropyl) isothiouronium chloride 1%
Sample 8 " 2%
30 Sample 9 " 4%
Sample lO2-(3-trimethoxysilylpropyl)-N-cetyl pyridinium bromide 1%
Sample ll " 2%
Sample 12 ~ 4%
3~
~. ..
.
. ~ .
- 13 ~ 21~4~62 WO92/1519~ PCT/US91/09116 EXAMPLE II
Nylon toothbrush bristle fibers were treated with the solutions of samples 1-3 by agitating the bristles in the respective solutions for about 30 minutes. The bristle fibers were removed from the solutions and dried at ambient conditions for about 3 hours. The fibers were then rinsed with deionized water and heated in an oven for about lO minutes at about 125C. The fibers were cooled at room temperature and the samples were place in inocula of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, respectively. The fibers were then removed from the inocula. One sample from each inoculum wa~ placed immediately in Letheen Broth, agitated, and a sample of the broth was then plated onto plate count agar via spiral plater. The numbers of colony forming units per milliliter were measured. Other samples from each inoculum were allowed to dry for l hour or 23 hours-before being placed in the Letheen Broth as described above. Bristle fibers not treated with the active agent 20 solutions were used as a control and evaluated in tandem with the treated bristles. The results are presented in Table II below.
: , ... ..
.
- ~
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. ~ .. ..
W O 92/15198 PCT~US91/09116 2~0~ 2 -Microorganism: Staphylococcus sureus SAMPLEINITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONTROL 2.7 X 1052.1 X 105-22.2 3.7 X 105 +37.0 ..
SAMPLE 3 2.4 X 1052.2 X 10~ -8.3 7.1 X 103 -97.0 SAMPLE 2 1.8 X 1051.4 X 105-22.2 1.2 X 104 -93.3 . _ SAMPLE 1 3.3 X 1052.6 X 105-21.2 6.5 x 104 -80.3 Microorganism: Pseudomonas aeruginosa S S
CONTROL 8.0 X 104.6 X 10 -42.5 1.9 X 103 -99.8 SAMPLE 3 5.5 X 103.1 X 10 -43.6 7.1 x lol -99 9 1~SAMPLE 2 3.6 X 1053.3 X 105 -8.3 5.4 X 10 -99.9 5 e SAMPLE 1 4.9 X 104.7 X 10~ -4.1 1.85 X 10 -99.9 Microorganlsm: Candida albicans - CONTROL 3.9 X 104 3.9 X 104 o 2.1 X 103 -94.6 SAMPLE 3 3.9 X 1044.1 X 104+5.1 9.8 x 10l -99.8 . _ SAMPL~ 2 5.9 X 1046.5 X 104+10.2 8.7 X 102 -98.5 SAMPLE 1 4.2 X 1043.2 X 104-23.8 3.1 X 103 -92.6 * (Colony forming units per ml.) - 15 - 21~4~2 EXAMPLE III
Following the procedures of Example II, toothbru-qh headq comprisçd of cellulose acetate propionate were treated with the solutions of Samples 1-3 and evaluated for antimicrobial activity. The r~sults are presented in Table III below.
TABLE III
Microorganism: Staphylococcus sure~s SAMPLE INITIAL* 1 H0UR* % CHANGE 23 HOUR* % CHANGE
CONTROL 12.0 X 1061.6 X 106 -20.0 1.9 X 106-5.0 CONTROL 22.0 X 1061.6 X 106 -20.0 1.8 X 10-10.0 SAHPLE 32.0 X 10 5.7 X 105 -71.5 8.7 X 10-99.9 .
SAMPLE 22.0 X 1066.7 X 105 -66.5 1.5 X lo2_99 9 SAMPLE 12.0 X 1065.5 X 105 -72.5 2.0 x 1o2_99.9 Microorganlsm: Pseudomonas aeruginosa : . -CONTROL 11.7 X 1061.2 X 106 -29.4 6.0 X 105-64.7 CONTR~L 21.7 X 1061.1 X 106 -35.3 3.8 x 105-77.7 SAMPLE 31.6 X 1061.2 X 106 -25.0 1.4 x 105-91.3 SAMPLE 21.7 X 1061.2 X 106 -29.4 5.0 X 104-97.1 2~ 5AMPLE 11.7 X 1061.2 X 10 -29.4 3.2 X 10-81.2 Microorganism: Candida albicans
US Patent No. 3,730,701 describes a method for controlling the growth of algae in water by adding certain silyl quaternary amines. US Patent No. 4,847,088 describes synergistic antimicrobial compositions comprising a quaternary ammonium compound and an acid : .. . .. . . :
.. . : . , :
. - . - . : ' . , :' , . :
.. . : : . . . . . .
.
WO92/15198 ~0 4 ~ 6 2 PCT/US91/09116 which are useful in treating carpets, fabrics, walls and furnishings.
Articles, such as "Disinfection of Water with Quaternary Ammonium Salts Insolubilized on a Porous Glass Surface," Nakagawa et al, A~plied and Environmental Microbioloay, March 1984, p-513-518; and "Algicidal Activity of a Surface-Bonded Organosilicone Quaternary Ammonium Chloride," Walters et al, AP~lied MicrobioloqY, Feb. 1973, P. 253~256 describe the antimicrobial activity ~0 of bound quaternary ammonium salts.
' :, , - : ~ , ~1 ~Lll~ 6 2 WO92/15198 PCT/US91/09]16 DETAILED DESCRI_TION
The present invention relates to personal and oral hygiene products which have been treated to bond active agent(s)to their surfaces. Specifically, the present invention involves an article comprised of polymeric material having bonded to the surface thereof one or more chemically or biologically active agent(s), wherein said article is suitable for oral or personal hygiene use, and said active agent is substantially l0 non-leachable from the surface of said article in a water-based medium.
Articles covered by this invention include any article of manufacture which is suitable for oral or personal hygiene use. Oral hygiene as used herein means useful for cleaning and caring for the teeth, gums, dentures or any other parts of the oral cavity. Personal hygiene as used herein means useful for cleaning and caring for the hair, scalp, skin, ears, nose, eyes and other parts of the face and head. Preferred articles 20 within the scope of this invention include a toothbrush, dental floss, toothpick, comb, hair brush, razor, eyeglass lens and frames and contact lens.
Suitable articles according to this invention may be composed partly or entirely of a polymeric material or 2~ have an exterior surface comprised of a polymeric material. The polymeric material can be a natural or synthetic polymer. The polymeric material preferably is polyamides, polyacrylates, polyesters, polypropylenes, polystyrenes, styrene-acryl-onitrile copolymers, acrylonitrile-butadien-estyrene copolymers, cellulose esters and blends andcombinations thereof. The most preferred polymeric materials are nylon and cellulose acetate propionate.
3- An essential feature of this invention is that the article has permanently bonded to the polymeric surface thereof one or more chemically or biologically active agent(s). These active agent(s) are bonded to the polymeric surfaces of the article, such that the agent(s) are substantially non-leachable from the surface of said article in a water-based medium. Suitable active agents : :. ' . . .: .
,. . .
: . ~ -. : . . . ~ .
,, :,,;~ : ~ ' . ., :
' ! ' .
21i0~46~ - 6 -W092/1~198 PCT/US91/091]6 would include any compound(s) having antimicrobial activity and which are capable of being bonded to the polymeric surfaces of the article. Preferred active agents include the quaternary ammonium compounds, ; organosilicone quaternary ammonium compounds, cetyl pyridinium compounds, guanidine compounds, bis-guanidine compounds and isothiouronium halide compounds.
Preferred quaternary ammonium compounds useful for this invention have the formula:
~ r 1 1 ~
R3 - N+ - R4-Y X
Wherein Rl is CH2-phenyl or an alkyl group containing about 8-22 carbon atoms; R2 is methyl, ethyl or an alkyl group containing about 8-22 carbon atoms; R3 is methyl or ethyl; R4 is an alkyl group containing about 1-6 carbon atoms; X is an anion; and Y is a group having the structure:
-Z, -OH, -OR5, -OC(O)R6, -CN, O O O
D D
25O-S-OQ, -C-O-R7 -C_CH, -S-R8, -S-Rg, O
-S-Rl -N-Rll ~ ANl;s -CH=CH2, 5~ R6~ R7~ R5~ Rg, Rlo, Rll, R12, are alkyl groups containing about 1-12 carbon atoms or phenyl; Z is halogen and Q is hydrogen or a cation.
3~
.
- ~ ~
s W092/15198 2 1 ~ `~ 4 6 ~ PCT/US91/09116 The more preferred organosilicone quaternary ammonium compounds useful for this invention have the formula:
CH30)3 Si(CH2)n I R3 ~
wherein Rl, R2, and ~3 are as described above, X is an anion and n is an integer from about 1-6 (preferably 3-6).
The most preferred organosilicone quaternary .;
15 ammonium compounds are n-octadecyldimethyl[3-(trimethoxysilyl)propyl] ammonium chloride, n-tetradecyldimethyl [3-(trimethoxysilyl) propyl] ammonium chloride, n-decyldimethyl[3-(trimethoxy-silyl)propyl] ammonium chloride, n-didodecylmethyl[3-(tri-methoxysilyl)propyll ammonium chloride, and n-dodecyldi-2~ methyl¦3-(trimethoxysilyl)propyl] ammonium chloride. . :
Other active agents can include the nitrogen as part ~-of a heterocyclic system, such as a cetyl pyridinium compound. The preferred.cetyl pyridinium compound is 30 2-(3-trimethoxy-æilylpropyl)-N-cetyl pyridinium bromide.
The isothiouronium halide compounds are also suitable for use as active agents according to this invention. The preferred isothiouronium halide compound for u~e in this invention is (trimethoxysilylpropyl) isothiouronium chloride.
The articles of this invention have the active agent(s) bonded to the polymeric surfaces of the ... . , . , : , , :: .
- ~ . : :, . :
,, : .. : :
W092/15198 ~10 4 4 6 2 PCT/US91/09116 articles, such that the active agent(s) is permanently attached to the articles. To be suitable for oral and personal hygiene use, the articles must have the active agent(s) bonded to the polymeric surfaces thereof such that the agent(s) is substantially non-leachable in an aqueous medium. Thus, the articles have a polymeric surface which has permanent antibacterial and/or antimicrobial activity which can not be leached out by saliva, shampoos, shaving creams, toothpastes and other aqueous-containing mediums.
The active agents can be permanently attached to the polymeric surfaces of the articles by any suitable means, ~uch as chemical linking using multifunctional reactive -organics (such as bis-carbenes or bis-nitrenes), silane coupling systems, plasma activation, flame activation, chemical treatment and other polymer grafting techniques.
The preferred attachment mechanism is a silane coupling system. It is believed, although Applicant does 2~ not intend to be limited thereby, that the alkoxysilyl end of the active agent is hydrolyzed to the corresponding hydroxy component in the presence of water.
This component then reacts with the active -OH, amide or 30 other reactive sites on the polymeric material. Although the active agent can be bonded to the polymeric surface of the article by any type of bonding, it is preferred that the agent be covalently bonded to the polymeric surface of the article.
The present invention also includes a method for applying a coating of chemically or biologically active agent to an oral or personal hygiene article comprised of polymeric material. This method can involve permanently , :", .
W092~15198 ~ 4 6 2 PCT/US91/09116 bonding the active agent directly to the untreated surface of the article. The method can also comprise the steps of:
l. contacting said article with a solvent selected from the group consisting of an aqueous-based organic or inorganic acid, an aqueous-based alkaline hydroxide or an organic solvent, and 2. subsequently bonding said active agent to the surface of said article.
The invention also includes articles which have been treated by the above ~ethods.
l~ It iQ believed, although Applicant does not intend to be bound or limited hereby, that treating the polymeric surface sf the article with the solvent exposes or forms reactive sites on the polymeric surface to which the active agents can bond. Preferably, the polymeric surface of the article has greater than about 2% of the surface area containing active sites for bonding of the 2~ active agent; more preferably greater than about 5%.
Thus, suitable solvents for treating the polymeric surfaces of the article include any material which would expose or form reactive -OH, amide, or other reactive 30 sites on the polymeric surfaces for bonding of the active agents. Some examples of suitable solvents include aqueous-based organic and inorganic acids, aqueous-based alkaline hydroxides and organic solvents. The preferred acids are sulfuric and acetic acid. The preferred alkaline hydroxides are potassium hydroxide and sodium hydroxide. Preferred organic solvents include methanol, ethanol, isopropanol, acetone and ethyl acetate.
" " ~', ~
:' ' ` ', . . ' ' ' ' ' .' ~ ', ' " ;' ' ' " ' ' . ' ~ , : ' WO 92/15198 ~ 4 ~ 2 PCI`/US91/09116 The polymeric surfaces of the articles are contacte~
with the solvent for a sufficient time ranging anywhere from a few minutes to several hours. The solvents can be u~ed alone, in combination or sequentially.
In bonding the active agent to the polymeric surface of the article, the article can be contacted with the active agent for a sufficient time for the active agent 10 to bond to the surface. Preferably, the active agent is in a solution of water or other suitable solvent. The solution can contain the active agent in any concentration, but preferably contains from about 1% to about 4% wt./vol. of the active agent. After contacting the article with the solution of active agent for a sufficient period of time (preferably about 30 minutes or longer), the article can be dried, rinsed and c~red at an elevated temperature (preferably about 50-125C). The drying and curing conditions,such as temperature, time and humidity, should be selected such that the 2S dimensional stability of the article is not adversely affected.
The articles of this invention are effective against a wide variety of microbial species, and they 30 continuously inhibit the growth of microbial organi~ms on the surface thereof. The articles have demonstrated antimicrobial activity against Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Streptococcus mutans/faecalis and Klebsiella pneumoniae.
The following examples are presented to help demonstrate the present invention. The examples are intended to be illustrative and not in a limitative ,.
WO92/15198 ~ 4 4 6 ~
sense. This invention includes the embodiments described and exemplified herein and all equivalents thereof. All parts and percentages used in the examples are on a weight basis unless otherwise indicated.
~0 ~0 , . :~ . . ~ ,: ~ :, WO92/15198 2 1 ~ 6 2 PCT/US91/09116 EXAMPLE I
Various treatment solutions were prepared within the scope of this invention containing 1%, 2% and 4%
wt./vol., respectively, of the active agent. Each solution was prepared by mixing lO ml. of concentrated acetic acid and 2 grams of surfactant (Zonyl FSN from DuPont Co.) with deionized water, followed by either lO, 20 or 40 grams of the active agent, to make one liter of each solution. The solution is agitated for about 30 minute~ to hydrolyze the active agent.
These solutions are presented in Table I below:
~ .
TABLE I
Solution Active Aqent Amt. (Wt.~Vol.) Sample l n-octadecyldimethyl 13-(trimethoxy-silyl)propyl] ammonium chloride 1%
20 Sample 2 " 2%
Sample 3 " 4%
Sample 4 n-tetradecyldimethyl ]3-trimethoxy-silyl)propyl] ammonium chloride 1%
2~ Sample 5 " 2%
Sample 6 " 4%
Sample 7(trimethoxysilylpropyl) isothiouronium chloride 1%
Sample 8 " 2%
30 Sample 9 " 4%
Sample lO2-(3-trimethoxysilylpropyl)-N-cetyl pyridinium bromide 1%
Sample ll " 2%
Sample 12 ~ 4%
3~
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.
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- 13 ~ 21~4~62 WO92/1519~ PCT/US91/09116 EXAMPLE II
Nylon toothbrush bristle fibers were treated with the solutions of samples 1-3 by agitating the bristles in the respective solutions for about 30 minutes. The bristle fibers were removed from the solutions and dried at ambient conditions for about 3 hours. The fibers were then rinsed with deionized water and heated in an oven for about lO minutes at about 125C. The fibers were cooled at room temperature and the samples were place in inocula of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, respectively. The fibers were then removed from the inocula. One sample from each inoculum wa~ placed immediately in Letheen Broth, agitated, and a sample of the broth was then plated onto plate count agar via spiral plater. The numbers of colony forming units per milliliter were measured. Other samples from each inoculum were allowed to dry for l hour or 23 hours-before being placed in the Letheen Broth as described above. Bristle fibers not treated with the active agent 20 solutions were used as a control and evaluated in tandem with the treated bristles. The results are presented in Table II below.
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W O 92/15198 PCT~US91/09116 2~0~ 2 -Microorganism: Staphylococcus sureus SAMPLEINITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONTROL 2.7 X 1052.1 X 105-22.2 3.7 X 105 +37.0 ..
SAMPLE 3 2.4 X 1052.2 X 10~ -8.3 7.1 X 103 -97.0 SAMPLE 2 1.8 X 1051.4 X 105-22.2 1.2 X 104 -93.3 . _ SAMPLE 1 3.3 X 1052.6 X 105-21.2 6.5 x 104 -80.3 Microorganism: Pseudomonas aeruginosa S S
CONTROL 8.0 X 104.6 X 10 -42.5 1.9 X 103 -99.8 SAMPLE 3 5.5 X 103.1 X 10 -43.6 7.1 x lol -99 9 1~SAMPLE 2 3.6 X 1053.3 X 105 -8.3 5.4 X 10 -99.9 5 e SAMPLE 1 4.9 X 104.7 X 10~ -4.1 1.85 X 10 -99.9 Microorganlsm: Candida albicans - CONTROL 3.9 X 104 3.9 X 104 o 2.1 X 103 -94.6 SAMPLE 3 3.9 X 1044.1 X 104+5.1 9.8 x 10l -99.8 . _ SAMPL~ 2 5.9 X 1046.5 X 104+10.2 8.7 X 102 -98.5 SAMPLE 1 4.2 X 1043.2 X 104-23.8 3.1 X 103 -92.6 * (Colony forming units per ml.) - 15 - 21~4~2 EXAMPLE III
Following the procedures of Example II, toothbru-qh headq comprisçd of cellulose acetate propionate were treated with the solutions of Samples 1-3 and evaluated for antimicrobial activity. The r~sults are presented in Table III below.
TABLE III
Microorganism: Staphylococcus sure~s SAMPLE INITIAL* 1 H0UR* % CHANGE 23 HOUR* % CHANGE
CONTROL 12.0 X 1061.6 X 106 -20.0 1.9 X 106-5.0 CONTROL 22.0 X 1061.6 X 106 -20.0 1.8 X 10-10.0 SAHPLE 32.0 X 10 5.7 X 105 -71.5 8.7 X 10-99.9 .
SAMPLE 22.0 X 1066.7 X 105 -66.5 1.5 X lo2_99 9 SAMPLE 12.0 X 1065.5 X 105 -72.5 2.0 x 1o2_99.9 Microorganlsm: Pseudomonas aeruginosa : . -CONTROL 11.7 X 1061.2 X 106 -29.4 6.0 X 105-64.7 CONTR~L 21.7 X 1061.1 X 106 -35.3 3.8 x 105-77.7 SAMPLE 31.6 X 1061.2 X 106 -25.0 1.4 x 105-91.3 SAMPLE 21.7 X 1061.2 X 106 -29.4 5.0 X 104-97.1 2~ 5AMPLE 11.7 X 1061.2 X 10 -29.4 3.2 X 10-81.2 Microorganism: Candida albicans
4 5 C0NTROL 12.0 X 106.0 X 10 -70.0 7.8 X 10+290.0 CONTROL 21.9 X 1056.4 X 104 -66.3 4.3 x 105+126.3 30 SAMPLE 32.4 X 1055.1 X 104 -78.8 1.5 x 103-99.4 .
SA~PLE 2_1.6 X 1053.4 X 104 -78.8 1.6 X 101_99 9 SAMPLE 11.7 X 1055.5 X 104 -67.7 Z.4 X lo2_99 9 * (Colony forming units per ml.) - .: .
- : '' ,, , ' ' ' ~ : '' :~ :
WO92/15198 21~62 16 - PCT/US91/09]16 EX~MPLE IV
Following the procedures of Example II, toothbrush headR compri~ed of cellulose acetate propionate were treated with the solutions of samples 4-6 and evaluated for antimicrobial activity. The results are present in Table IV below.
TABLE IV
Microorganism: Staphylococcus aureas SAMPLE INITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONIROL 5.1 X 105 7.5 X 105 +47.1 4.9 X 105-3.9 . _ SAMPLE 6 4.2 X 105 8.8 X 104 -79.1 1.5 X lo2-99 9 _ ~3 SAHPLE 5 5.4 X 10 3.~ X 105 -35.2 1.8 X 105-66.7 -SAMPLE 4 3.3 X 105 2.9 X 105 -12.1 1.1 x 103-99.7 Microorganism: Pseudomonas Aeruginosa CONTROL 7.9 X 105 5.9 X 105 -25.3 1 8 X 102-99 9 ---SAHPLE 6 7.5 X 105 6.1 X 105 -18.7 6.4 x lo2-99 9 SAMPLE 5 7.9 X 105 6.9 X 105 -12.7 1.8 X 103-99.8 .
SAMPLE 4 8.0 X 105 6.6 X 105 -17.5 1.6 X 102_99.9 Microorgan$sm: Candlda albicans CONTROL 5.5 X 10 5.5 X 10 01.1 X 10 -98.0 SAMPLE 6 1.1 X 10 6.7 X 103 -39.1 0 -100.0 . _ . _ . _ SAMPLE 5 1.5 X 10 9.5 X 103 -36.7 7.1 X 101 -99.5 30 ~AMPLE 4 8.5 X 103 5.7 X 103 -32.9 0 -100.0 * (Colony forming units per ml.) ~ - . , ,:, : ..
,: , .: ': ' . ~ : ~
. . . : :. -: .,;~ :
- 17 ~ 2 1 ~4~2 W O 92/15198 ` PCT/US91/09116 E~MPLE V
Following the procedures of Example II, toothbrush heads comprised of cellulose acetate propionate were treated with the ~olutions of Samples 7-9 and evaluated for antimicrobial activity. The results are presented in Table V below.
TABLE V
~0 Microorganism: Stsphylococcus aureas SAMPLE INITIAL* 1 HOUR*% CHANGE 23 HOUR* % CHANGE
CONTROL 5.7 X 105 4.9 X 105 -13.6 1.2 X 106 +102.4 :
SAMPLE 9 5.7 X 105 4.0 X 10-93.0 5.2 X 103-99.1 1~ SAMPLE 8 6.6 X 105 1.8 X 104 -97.3 1.9 X 104 -97.1 SAMPLE 7 6.9 X 105 4.8 X 105 -99.3 9.8 x 105 +41.0 .
Microorganlsm: Pseudomonas aeruginosa CONTROL 2.1 X 106 2.2 X 106 +5.3 2.3 X 105 -88.7 SAMPLE 9 2.2 X 106 2.1 X 10-3.2 4.4 x lol-99 9 SAMPLE 8 2.2 X 106 2.1 X 106 -5.5 7.3 X 104 -96.6 SAMPLE 7 2.2 X 106 2.2 X 106 0 3.8 X 103 -99.8 _ 2~ Microorganism: Candida albicans CONTROL 1.4 X 10 6.4 X 10-54.5 2.1 X 10-85.1 SAMPLE 9 6.3 X 10 4.6 X 102 -92.7 1.1 X 101 -99.8 SAMPLE 8 1.5 X 104 2.0 X 103 -86.5 1.1 X 103 -92.7 30 SAMPLE 7 2.4 X 104 7.1 X 104 +195.43.3 X 104 +37.9 . . .
* tColonY forming units per ml.) f -' - ~'., ' .
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WO92/15198 2 1 0 ~ ' ~ '' PCT/US91/09116 _ ~ J h EXAMPLE VI
Following the procedur~s of Example III, toothbrush heads compri~ed of cellulose acetate propionate were treated with the solutions of Samples 10-12 and evaluated for antimicrobial activity. The results are pre~ented in Table VI below.
TAB~ VI
Microorganism: Staphylococcus aureas 10 SAHpLE INITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONTROL 2.9 X 105 2.0 X 105 -31.02.2 X 105 -24.1 .
SAMPLE 12 2.7 X 105 1.4 X 105 -48.11.7 X 104 -93.7 .
SAMPLE 11 3.1 X 105 2.1 X 105 -32.32.0 X 104 -93.6 ''SAMPLE 10 3.2 X 105 2.4 X 105 -25.04.8 x 104 -85.0 Microorganism: Pseudomonas aeruginosa . .
CONTROL 6.7 X 105 6.4 X 105 -4.5 2.7 X 103 -99.6 SAMPLE 12 6.8 X 105 6.9 X 105 +1.5 3.9 x lo2 -99 9 SAHPLE 11 6.0 X 105 4.5 X 105 -25.0 7.1 X 103 -99.9 SAMPLE 10 8.7 X 105 6.7 X 105 -23.0 2.1 X 103 -99.8 . _ Microorganism: Candida albicans 2~CONTROL 3.5 X 10 3.1 X 10 -11.41.4 X 10 -99.6 .
SAMPLE 12 4.4 X 10~ 2.5 X 104 -43.22.9 X lo2 -99 3 SAMPLE 11 3.3 X 104 3.2 X 104 -3.0 6.0 X 102 -98.2 SAHPLE 10 4.0 X 104 3.4 X 104 -15.09.7 X 102 -99.6 30 - _ * (Colony forming units per ml.) :. . : .
, - , : . :
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- 19 - 21 ~ 62 W092/lS198 PCT/US91/Ogll6 EXAMPLE VII
Toothbrush heads comprised of cellulose acetate propionate,and treated with the solution of Sample 3 according to the procedures of Example II, were evaluated for leachability of the active agent. Some of these treated toothbrush heads were washed several times with water, while others were unwashed.
The washed and unwashed toothbrush heads were evaluated for leachability using a bromophenol blue 10 colorimetric analytical method. A bromophenol blue solution was prepared by mixing 0.1125 grams bromophenol blue, 450 grams of deionized water and 0.75 ml. of 10%
Na2C03. Two of the washed toothbrush heads were placed in a 4-ounce french square bottle along with 50 ml. of the bromophenol blue solution and 2 ml. of 2% Triton X-100 wetting agent. Two of the unwashed toothbrush heads were also placed in a similar bottle with 50 ml. of the bromophenol blue solution and Triton wetting agent.
The bottles were shaken for about 20 minutes and allowed to sit. After periods of 1-hour, 12-hours and 24-hours, solution from each bottle was poured into cuvets and the transmittance measured on a spectrophotometer at 589 nanometers.
In the procedure, the blue dye reacts with the bound 2~ active agent on the toothbrush heads, causing a decrease in the bromophenol blue solution's color intensity. This loss of color intensity is a quantitative measure of the amount of active agent bonded to the surface of the toothbrush heads.
~0 The results of the evaluation are presented in Table VII below.
(Absorbance Units) Sampling Time in Hours SamDle (0) (1) (12) (24) A. Washed Toothbrush Heads 0.32 0.30 0.31 0.33 B. Unwashed Toothbrush Heads 0.31 0.30 0.33 0.33 C. Bromophenol Blue Solution 0.53 0.53 0.53 0.53 Control (sample to sample variation is less than ~ 0.02 absorbance units) , ,. . , : ~ - .
,.
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', , ' ,: . ........ . .. , . . , , . , ' , ' WO92/15198 2 1 0 ~ ~ 6 2 - 20 - PCT/US91/09116 The above results show no significant differenc between the washed and unwashed toothbrush heads, indicating no leaching of the active agent initially or over time.
i SUBSTITUTE SHEET
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SA~PLE 2_1.6 X 1053.4 X 104 -78.8 1.6 X 101_99 9 SAMPLE 11.7 X 1055.5 X 104 -67.7 Z.4 X lo2_99 9 * (Colony forming units per ml.) - .: .
- : '' ,, , ' ' ' ~ : '' :~ :
WO92/15198 21~62 16 - PCT/US91/09]16 EX~MPLE IV
Following the procedures of Example II, toothbrush headR compri~ed of cellulose acetate propionate were treated with the solutions of samples 4-6 and evaluated for antimicrobial activity. The results are present in Table IV below.
TABLE IV
Microorganism: Staphylococcus aureas SAMPLE INITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONIROL 5.1 X 105 7.5 X 105 +47.1 4.9 X 105-3.9 . _ SAMPLE 6 4.2 X 105 8.8 X 104 -79.1 1.5 X lo2-99 9 _ ~3 SAHPLE 5 5.4 X 10 3.~ X 105 -35.2 1.8 X 105-66.7 -SAMPLE 4 3.3 X 105 2.9 X 105 -12.1 1.1 x 103-99.7 Microorganism: Pseudomonas Aeruginosa CONTROL 7.9 X 105 5.9 X 105 -25.3 1 8 X 102-99 9 ---SAHPLE 6 7.5 X 105 6.1 X 105 -18.7 6.4 x lo2-99 9 SAMPLE 5 7.9 X 105 6.9 X 105 -12.7 1.8 X 103-99.8 .
SAMPLE 4 8.0 X 105 6.6 X 105 -17.5 1.6 X 102_99.9 Microorgan$sm: Candlda albicans CONTROL 5.5 X 10 5.5 X 10 01.1 X 10 -98.0 SAMPLE 6 1.1 X 10 6.7 X 103 -39.1 0 -100.0 . _ . _ . _ SAMPLE 5 1.5 X 10 9.5 X 103 -36.7 7.1 X 101 -99.5 30 ~AMPLE 4 8.5 X 103 5.7 X 103 -32.9 0 -100.0 * (Colony forming units per ml.) ~ - . , ,:, : ..
,: , .: ': ' . ~ : ~
. . . : :. -: .,;~ :
- 17 ~ 2 1 ~4~2 W O 92/15198 ` PCT/US91/09116 E~MPLE V
Following the procedures of Example II, toothbrush heads comprised of cellulose acetate propionate were treated with the ~olutions of Samples 7-9 and evaluated for antimicrobial activity. The results are presented in Table V below.
TABLE V
~0 Microorganism: Stsphylococcus aureas SAMPLE INITIAL* 1 HOUR*% CHANGE 23 HOUR* % CHANGE
CONTROL 5.7 X 105 4.9 X 105 -13.6 1.2 X 106 +102.4 :
SAMPLE 9 5.7 X 105 4.0 X 10-93.0 5.2 X 103-99.1 1~ SAMPLE 8 6.6 X 105 1.8 X 104 -97.3 1.9 X 104 -97.1 SAMPLE 7 6.9 X 105 4.8 X 105 -99.3 9.8 x 105 +41.0 .
Microorganlsm: Pseudomonas aeruginosa CONTROL 2.1 X 106 2.2 X 106 +5.3 2.3 X 105 -88.7 SAMPLE 9 2.2 X 106 2.1 X 10-3.2 4.4 x lol-99 9 SAMPLE 8 2.2 X 106 2.1 X 106 -5.5 7.3 X 104 -96.6 SAMPLE 7 2.2 X 106 2.2 X 106 0 3.8 X 103 -99.8 _ 2~ Microorganism: Candida albicans CONTROL 1.4 X 10 6.4 X 10-54.5 2.1 X 10-85.1 SAMPLE 9 6.3 X 10 4.6 X 102 -92.7 1.1 X 101 -99.8 SAMPLE 8 1.5 X 104 2.0 X 103 -86.5 1.1 X 103 -92.7 30 SAMPLE 7 2.4 X 104 7.1 X 104 +195.43.3 X 104 +37.9 . . .
* tColonY forming units per ml.) f -' - ~'., ' .
~. .
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WO92/15198 2 1 0 ~ ' ~ '' PCT/US91/09116 _ ~ J h EXAMPLE VI
Following the procedur~s of Example III, toothbrush heads compri~ed of cellulose acetate propionate were treated with the solutions of Samples 10-12 and evaluated for antimicrobial activity. The results are pre~ented in Table VI below.
TAB~ VI
Microorganism: Staphylococcus aureas 10 SAHpLE INITIAL* 1 HOUR* % CHANGE 23 HOUR* % CHANGE
CONTROL 2.9 X 105 2.0 X 105 -31.02.2 X 105 -24.1 .
SAMPLE 12 2.7 X 105 1.4 X 105 -48.11.7 X 104 -93.7 .
SAMPLE 11 3.1 X 105 2.1 X 105 -32.32.0 X 104 -93.6 ''SAMPLE 10 3.2 X 105 2.4 X 105 -25.04.8 x 104 -85.0 Microorganism: Pseudomonas aeruginosa . .
CONTROL 6.7 X 105 6.4 X 105 -4.5 2.7 X 103 -99.6 SAMPLE 12 6.8 X 105 6.9 X 105 +1.5 3.9 x lo2 -99 9 SAHPLE 11 6.0 X 105 4.5 X 105 -25.0 7.1 X 103 -99.9 SAMPLE 10 8.7 X 105 6.7 X 105 -23.0 2.1 X 103 -99.8 . _ Microorganism: Candida albicans 2~CONTROL 3.5 X 10 3.1 X 10 -11.41.4 X 10 -99.6 .
SAMPLE 12 4.4 X 10~ 2.5 X 104 -43.22.9 X lo2 -99 3 SAMPLE 11 3.3 X 104 3.2 X 104 -3.0 6.0 X 102 -98.2 SAHPLE 10 4.0 X 104 3.4 X 104 -15.09.7 X 102 -99.6 30 - _ * (Colony forming units per ml.) :. . : .
, - , : . :
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- 19 - 21 ~ 62 W092/lS198 PCT/US91/Ogll6 EXAMPLE VII
Toothbrush heads comprised of cellulose acetate propionate,and treated with the solution of Sample 3 according to the procedures of Example II, were evaluated for leachability of the active agent. Some of these treated toothbrush heads were washed several times with water, while others were unwashed.
The washed and unwashed toothbrush heads were evaluated for leachability using a bromophenol blue 10 colorimetric analytical method. A bromophenol blue solution was prepared by mixing 0.1125 grams bromophenol blue, 450 grams of deionized water and 0.75 ml. of 10%
Na2C03. Two of the washed toothbrush heads were placed in a 4-ounce french square bottle along with 50 ml. of the bromophenol blue solution and 2 ml. of 2% Triton X-100 wetting agent. Two of the unwashed toothbrush heads were also placed in a similar bottle with 50 ml. of the bromophenol blue solution and Triton wetting agent.
The bottles were shaken for about 20 minutes and allowed to sit. After periods of 1-hour, 12-hours and 24-hours, solution from each bottle was poured into cuvets and the transmittance measured on a spectrophotometer at 589 nanometers.
In the procedure, the blue dye reacts with the bound 2~ active agent on the toothbrush heads, causing a decrease in the bromophenol blue solution's color intensity. This loss of color intensity is a quantitative measure of the amount of active agent bonded to the surface of the toothbrush heads.
~0 The results of the evaluation are presented in Table VII below.
(Absorbance Units) Sampling Time in Hours SamDle (0) (1) (12) (24) A. Washed Toothbrush Heads 0.32 0.30 0.31 0.33 B. Unwashed Toothbrush Heads 0.31 0.30 0.33 0.33 C. Bromophenol Blue Solution 0.53 0.53 0.53 0.53 Control (sample to sample variation is less than ~ 0.02 absorbance units) , ,. . , : ~ - .
,.
. ~ - ,. . . . ~
... . ~ . .
', , ' ,: . ........ . .. , . . , , . , ' , ' WO92/15198 2 1 0 ~ ~ 6 2 - 20 - PCT/US91/09116 The above results show no significant differenc between the washed and unwashed toothbrush heads, indicating no leaching of the active agent initially or over time.
i SUBSTITUTE SHEET
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Claims (33)
1. An article comprised of polymeric material having bonded to the surface thereof one or more chemically or biologically active agent, wherein said article is suitable for oral or personal hygiene use, and said active agent is substantially non-leachable from the surface of said article by a water-based medium.
2. The article of Claim 1 wherein said polymeric material is selected from the group consisting of polyamides, polyacrylates, polyesters, polypropylenes, cellulose esters, polystyrenes, styrene-acrylonitrile copolymers, acrylonitrile-butadiene-styrene copolymers and mixtures thereof.
3. The article of Claim 2 wherein said polymeric material is nylon.
4. The article of claim 2 wherein said polymeric material is cellulose acetate propionate.
5. The article of claim 1 wherein said active agent is covalently bonded to the polymeric surface thereof.
6. The article of claim 1 where said article is a toothbrush.
7. The article of claim 1 wherein said article is dental floss.
8. The article of claim 1 wherein said article is a toothpick.
9. The article of claim 1 wherein said article is a comb.
10. The article of claim 1 wherein said article is a hair brush.
11. The article of claim 1 wherein said article is razor.
12. The article of claim 1 wherein said article is a contact lens.
13. The article of claim 1 wherein said article is eye glasses.
14. The article of claim 1 wherein said active agent is a quaternary ammonium compound.
15. The article of claim 14 wherein said active agent is a quaternary ammonium compound having the formula:
wherein R1 is CH2-phenyl or an alkyl group containing about 8-22 carbon atoms; R2 is methyl, ethyl or an alkyl group containing about 8-22 carbon atoms; R3 is methyl or ethyl; R4 is an alkyl group containing about 1-6 carbon atoms; X is an anion;
and Y is a group having the structure:
-Z, -OH, -OR5, -OC(O)R6, -CN, , -C?CH, -S-R8, , , , AND -CH=CH2, wherein R5, R6, R7, R8, R9, R10, R11, R12 are alkyl groups containing about 1-12 carbon atoms or phenyl;
Z is halogen and Q is hydrogen or a cation.
wherein R1 is CH2-phenyl or an alkyl group containing about 8-22 carbon atoms; R2 is methyl, ethyl or an alkyl group containing about 8-22 carbon atoms; R3 is methyl or ethyl; R4 is an alkyl group containing about 1-6 carbon atoms; X is an anion;
and Y is a group having the structure:
-Z, -OH, -OR5, -OC(O)R6, -CN, , -C?CH, -S-R8, , , , AND -CH=CH2, wherein R5, R6, R7, R8, R9, R10, R11, R12 are alkyl groups containing about 1-12 carbon atoms or phenyl;
Z is halogen and Q is hydrogen or a cation.
16. The article of claim 1 wherein said active agent is organosilicone quaternary ammonium compound.
17. The article of claim 16 wherein said organosilicone quaternary ammonium compound has the formula:
wherein R1 is -CH2-phenyl or an alkyl group having from about 8-22 carbon atoms, R2 is a methyl, ethyl or an alkyl group containing about 8-22 carbon atoms, R3 is methyl or ethyl, X is an anion and n is an integer from about 1-6.
wherein R1 is -CH2-phenyl or an alkyl group having from about 8-22 carbon atoms, R2 is a methyl, ethyl or an alkyl group containing about 8-22 carbon atoms, R3 is methyl or ethyl, X is an anion and n is an integer from about 1-6.
18. The article of claim 16 wherein said organosilicone quaternary ammonium compound is n-octadecyldimethyl [3-(trimethoxysilyl)propyl] ammonium chloride
19. The article of claim 16 wherein said organosilicone quaternary ammonium compound is n-tetradecyldimethyl [3-(trimethoxysilyl) propyl] ammonium chloride.
20. The article of claim 1 wherein said active agent is (trimethoxysilylpropyl) isothiouronium chloride.
21. The article of claim 1 wherein said active agent is 2-(3-trimethoxysilylpropyl)-N-cetyl pyridinium bromide. 22. The article of claim 1 wherein said polymeric material is treated by contact with a solvent selected from the group consisting of an aqueous-based organic or inorganic acid, an aqueous-based alkaline hydroxide and an organic solvent, and subsequently said active agent is bonded to the surface of said treated polymeric material.
WO 92/15198 PCT/US91/09116
23. The article of claim 22 wherein said acid is selected from the group consisting of sulfuric acid and acetic acid.
24. The article of claim 22 wherein said alkaline hydroxide is elected from the group consisting of potassium hydroxide and sodium hydroxide.
25. The article of claim 22 wherein said organic solvent is selected from the group consisting of methanol, ethanol, isopropanol, acetone and ethyl acetate.
26. The article of claim 22 wherein said active agent is selected from the group consisting of n-octadecyldimethyl[3-(trimethoxysilyl)propyl]
ammonium chloride, n-tetradecyldimethyl [3-(trimethoxysilyl) propyl] ammonium chloride, 2-(3-trimethoxysilylpropyl)-N-cetyl pyridinium bromide, and (trimethoxysilylpropyl) isothiouronium chloride.
ammonium chloride, n-tetradecyldimethyl [3-(trimethoxysilyl) propyl] ammonium chloride, 2-(3-trimethoxysilylpropyl)-N-cetyl pyridinium bromide, and (trimethoxysilylpropyl) isothiouronium chloride.
27. A method for applying a coating of chemically or biologically active agent to an oral or personal hygiene article comprised of polymeric material comprising permanently bonding said active agent to the surface of said article.
28. The method of claim 27 comprising the steps of:
1) contacting said article with a solvent selected from the group consisting of an aqueous-based organic or inorganic acid, an aqueous-based alkaline hydroxide and an organic solvent; and 2) subsequently bonding said active agent to the surface of said article.
1) contacting said article with a solvent selected from the group consisting of an aqueous-based organic or inorganic acid, an aqueous-based alkaline hydroxide and an organic solvent; and 2) subsequently bonding said active agent to the surface of said article.
29. The method of claim 27 wherein said article is selected from the group consisting of toothbrushes, toothpicks, dental floss, dentures, hair combs, hair brushes, razors, eye glasses and contact lens.
30. The method of claim 27 where said polymeric material is nylon.
31. The method of claim 27 wherein said polymeric material is cellulose acetate propionate.
32. The method of claim 27 wherein said active agent is selected from the group consisting of n-octadecyldi-methyl[3-(trimethoxysilyl)propyl] ammonium chloride, n-tetradecyldimethyl [3-(trimethoxysilyl) propyl]
ammonium chloride, n-dodecyldimethyl[3-(trimethoxy-silyl)propyl] ammonium chloride, n-didodecylmethyl [3-(trimethoxysilyl)propyl] ammonium chloride, 2-(3-trimethoxysilylpropyl)-N-cetyl pyridinium bromide, and (trimethoxysilylpropyl) isothiouronium chloride.
ammonium chloride, n-dodecyldimethyl[3-(trimethoxy-silyl)propyl] ammonium chloride, n-didodecylmethyl [3-(trimethoxysilyl)propyl] ammonium chloride, 2-(3-trimethoxysilylpropyl)-N-cetyl pyridinium bromide, and (trimethoxysilylpropyl) isothiouronium chloride.
33. The method of claim 28 wherein said solvent is selected from the group consisting of sulfuric acid, acetic acid, potassium hydroxide, sodium hydroxide, methanol, ethanol, isopropanol, acetone and ethyl acetate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US66287091A | 1991-03-01 | 1991-03-01 | |
| US662,870 | 1991-03-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2104462A1 true CA2104462A1 (en) | 1992-09-02 |
Family
ID=24659580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002104462A Abandoned CA2104462A1 (en) | 1991-03-01 | 1991-12-05 | Oral and personal hygiene articles containing active agents bonded to the surface thereof |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0586384A1 (en) |
| JP (1) | JPH06506197A (en) |
| AU (1) | AU1259892A (en) |
| BR (1) | BR9107297A (en) |
| CA (1) | CA2104462A1 (en) |
| MX (1) | MX9200893A (en) |
| NZ (1) | NZ241780A (en) |
| WO (1) | WO1992015198A1 (en) |
| ZA (1) | ZA921537B (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2695800B1 (en) * | 1992-09-23 | 1996-03-08 | Inst Textile De France | ANTISEPTIC COMPOUND. |
| US5340583A (en) * | 1993-05-06 | 1994-08-23 | Allergan, Inc. | Antimicrobial lenses and lens care systems |
| FR2718330B1 (en) * | 1994-04-07 | 1998-10-02 | Transphyto Sa | Antiseptic items. |
| US6295733B1 (en) | 1994-08-03 | 2001-10-02 | Warner-Lambert Company | Changeable color shaving aid |
| DE19643019C1 (en) * | 1996-10-18 | 1998-04-16 | Georg Wiegner | toothbrush |
| JP4103175B2 (en) * | 1998-05-20 | 2008-06-18 | 東レ株式会社 | Production method of polymer for ophthalmic lens |
| US6592814B2 (en) | 1998-10-02 | 2003-07-15 | Johnson & Johnson Vision Care, Inc. | Biomedical devices with antimicrobial coatings |
| JP4392773B2 (en) * | 2000-03-16 | 2010-01-06 | 富士フイルム株式会社 | Photoelectric conversion element and photoelectrochemical cell |
| US8172395B2 (en) | 2002-12-03 | 2012-05-08 | Novartis Ag | Medical devices having antimicrobial coatings thereon |
| DE102007054133A1 (en) | 2007-11-14 | 2009-05-20 | Mitsubishi Polyester Film Gmbh | Antimicrobially finished, coated, biaxially oriented polyester film |
| MY159356A (en) | 2008-06-04 | 2016-12-30 | Colgate Palmolive Co | Oral care implement with cavitation system |
| WO2013079957A1 (en) * | 2011-11-30 | 2013-06-06 | Coventry University | Antimicrobial animal product |
| CN110194889B (en) * | 2018-02-27 | 2022-11-15 | 嘉丰工业科技（惠州）有限公司 | Method for preparing modified thermoplastic plastic and product with microorganism adhesion resistance and composition for preparing modified thermoplastic plastic |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2938814A (en) * | 1954-07-19 | 1960-05-31 | Gallowhur Chemical Corp | Method of producing antiseptic articles |
| FR1274388A (en) * | 1957-10-31 | 1961-10-27 | Du Pont | Biologically active graft copolymer, and method of preparation thereof |
| US4035146A (en) * | 1975-10-20 | 1977-07-12 | Schwarz Services International Ltd. | Binding of antimicrobial compounds to a hydroxyl containing substrate with cyanuric chloride |
| US4259103A (en) * | 1979-03-12 | 1981-03-31 | Dow Corning Corporation | Method of reducing the number of microorganisms in a media and a method of preservation |
| US4472327A (en) * | 1983-01-31 | 1984-09-18 | Neefe Charles W | Method of making hydrogel cosmetic contact lenses |
| US4615937A (en) * | 1985-09-05 | 1986-10-07 | The James River Corporation | Antimicrobially active, non-woven web used in a wet wiper |
| DE3720555A1 (en) * | 1987-06-22 | 1989-01-05 | Henkel Kgaa | USE OF INSOLUBLE, POLYFUNCTIONAL QUARTAINE AMMONIUM COMPOUNDS FOR ADSORPTIVE BINDING OF MICROORGANISMS |
| WO1989004330A1 (en) * | 1987-11-06 | 1989-05-18 | Ioptex Research, Inc. | Surface modified optical lens and method of surface modification |
| CA1334506C (en) * | 1988-08-22 | 1995-02-21 | William Curtis White | Method of inhibiting the spread of disease and infection in structures |
| JP2608131B2 (en) * | 1989-03-14 | 1997-05-07 | サンスター株式会社 | toothbrush |
-
1991
- 1991-12-05 JP JP4505234A patent/JPH06506197A/en active Pending
- 1991-12-05 BR BR9107297A patent/BR9107297A/en unknown
- 1991-12-05 WO PCT/US1991/009116 patent/WO1992015198A1/en not_active Application Discontinuation
- 1991-12-05 CA CA002104462A patent/CA2104462A1/en not_active Abandoned
- 1991-12-05 AU AU12598/92A patent/AU1259892A/en not_active Abandoned
-
1992
- 1992-02-28 NZ NZ241780A patent/NZ241780A/en unknown
- 1992-02-28 ZA ZA921537A patent/ZA921537B/en unknown
- 1992-02-28 MX MX9200893A patent/MX9200893A/en unknown
- 1992-09-19 EP EP92904862A patent/EP0586384A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO1992015198A1 (en) | 1992-09-17 |
| EP0586384A1 (en) | 1994-03-16 |
| AU1259892A (en) | 1992-10-06 |
| ZA921537B (en) | 1992-11-25 |
| NZ241780A (en) | 1994-11-25 |
| JPH06506197A (en) | 1994-07-14 |
| MX9200893A (en) | 1992-09-01 |
| BR9107297A (en) | 1994-06-14 |
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