CN1374874A - Use of fatty acid/amino acid soaps to enhance antimicrobial effectiveness of topical pharmaceutical compositions - Google Patents

Use of fatty acid/amino acid soaps to enhance antimicrobial effectiveness of topical pharmaceutical compositions Download PDF

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CN1374874A
CN1374874A CN00813117A CN00813117A CN1374874A CN 1374874 A CN1374874 A CN 1374874A CN 00813117 A CN00813117 A CN 00813117A CN 00813117 A CN00813117 A CN 00813117A CN 1374874 A CN1374874 A CN 1374874A
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fatty acid
acid
amino acid
agent
raising
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E·J·卡斯特罗
S·H·格尔森
W·W·汉
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Alcon Vision LLC
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Alcon Laboratories Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Ophthalmology & Optometry (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Fatty acid/amino acid soaps are used to enhance antimicrobial effectiveness in topically administrable pharmaceutical compositions containing at least one active ingredient, a cationic preservative and an anionic polyelectrolyte, such as a carboxyvinyl polymer, xanthan gum, polystyrene sulfonic acid polymer or cationic exchange resin.

Description

Use fatty acid/acid/amino acid soaps to improve the antibacterial efficacy of local medicine composition
The application requires the rights and interests of the common unsettled U.S. Provisional Application serial number 60/105,855 of submission on October 27th, 1998.
Invention field
The present invention relates generally to the preservation of pharmaceutical composition.But the present invention is specifically related to use fatty acid/acid/amino acid soaps to prevent or reduces the antibacterial components and combining of contained other components wherein of the pharmaceutical composition of topical, thereby improves the antibacterial efficacy of this based composition.
In recent years, proposed many ophthalmic compositions, it contains various components, as carboxy vinyl polymer (as Carbopol ), ion exchange resin is (as Amberlite ) or other big polyelectrolyte, these components provide the lasting release of ophthalmic remedy, and have increased patient's comfortableness.This based composition for example is described in US4, among 911,920 (people such as Jani).Although these compositionss are comfortable and have lasting release characteristics, the cationic antibacterial agent that the antiseptic of this based composition of Chang Zuowei adds is tending towards combining with the anionic polyelectrolyte that exists in the preparation as Benasept (BAC), causes the forfeiture of antibacterial efficacy.
Sarcosinate surfactant is made up of the acidylate sarcosine.Sarcosine (CH 3-NH-CH 2-COOH) be the aminoacid of finding in a kind of be everlasting Asterias amurensis Lutken and the Hemicentrotus seu Strongylocentrotus, with glycine (NH 2-CH 2-COOH) chemistry is relevant, and the latter is the basic amino acid in the mammal.The common fatty acids and the derivant thereof that are used to make sarcosinate surfactant are lauric acid, oleic acid and myristic acid and ester and halogenide.Because its character gentleness, sarcosinate surfactant has been used for shampoo, collutory, skin detergents, sunscreen, aerosol have a shave foam and other personal care products.Up to now, the main application of this class surfactant is in cosmetics industry.For example, transfer Procter ﹠amp; The european patent application 0 194 097 of Gamble (people such as Schmidt) is mentioned sodium lauroyl sarcosine and is used for aerosol skin detergents and humidification mousse (moisturizer mousse) as gentle anion surfactant.
United States Patent (USP) 5,520,920 people such as () Castillo disclose the antibacterial efficacy that uses some modification sarcosinate and lactate (lactylate) to improve ophthalmic composition, especially in cationic preservative otherwise can with the bonded situation of anionic polyelectrolyte under.The modification sarcosinate has following formula: Wherein: R 1=C 4-C 27Saturated or unsaturated hydrocarbons;
M=H or officinal salt; With
N=1,2 or 3.
Representational modification sarcosinate comprises with Hamposyl Those that trade name is sold are as Hamposyl L (Hamposyl L), N-Oleoylsarcosine (Hamposyl O), myristoyl-N-methylaminoacetic acid (Hamposyl M), Cortex cocois radicis acyl group (cocoyl) sarcosine (Hamposyl C), Hamposyl S (Hamposyl S) and nonanoyl (pelargodoyl) sarcosine (Hamposyl P).Representative lactate comprises decoyl sodium lactate (Pationic 122A).
But need be to other solutions of cationic preservative-anionic polyelectrolyte in the pharmaceutical composition of topical in conjunction with this problem.
Fatty acid/acid/amino acid soaps is known and comprises for example with Aminosoap Trade name (the Ajinomoto Co. of Tokyo, Inc.) those surfactants of Xiao Shouing.Produce handbook, Aminosoap according to it Surfactant is used for hair and body care (hair shampoo, bath gel and bath bubble), facial-care (facial cleansing agent, foaming mousse cleanser, Cleansing Foam (creme) and makeup removing liquid) and domestic and health care.
Summary of the invention
But the invention provides the method for antiseptic effect of pharmaceutical composition that a kind of raising contains the topical of anionic polyelectrolyte and cationic preservative.According to the inventive method, but fatty acid/acid/amino acid soaps is added in the pharmaceutical composition of topical.
Although the applicant does not wish to be confined to specific theory, it is believed that and to cause bonded cationic preservative being discharged from anionic polyelectrolyte in fatty acid/acid/amino acid soaps adding compositions by forming loose and reversible surfactant-antiseptic coordination compound.This surfactant-antiseptic coordination compound has antibacterial efficacy.In addition, this soap class self may have antibacterial activity.
No matter mechanism how, but fatty acid/acid/amino acid soaps of the present invention has improved the antiseptic effect of the pharmaceutical composition of topical.Therefore, but the invention still further relates to the pharmaceutical composition of the topical that contains one or more pharmaceutically active agents, anionic polyelectrolyte, cationic preservative and fatty acid/acid/amino acid soaps.Detailed Description Of The Invention
Except as otherwise noted, all formula components amounts of representing with percent are w/w.
Fatty acid/the acid/amino acid soaps that can be used in the protective system of the present invention is more such, and wherein fatty acid component is derived from C 8-C 24Fatty acid and amino acid composition are selected from lysine and arginine.The preferred fat acid constituents is selected from Cortex cocois radicis acyl group, inferior oleoyl, lauroyl, myristoyl, stearyl, oleoyl and pelargonyl group (pelargodoyl) fatty acid residue.This type of fatty acid/acid/amino acid soaps is commercially available or can be prepared by known method.For example wherein fatty acid component be Cortex cocois radicis acyl group and amino acid composition be derived from arginic soap can AMINOSOAP AR-12 available from Ajinomoto Co., Inc. (Tokyo).Wherein to be that Cortex cocois radicis acyl group and amino acid composition are derived from the soap of lysine can AMINOSOAP LYC-12 commercial for fatty acid component.
Usually, the amount of fatty acid/acid/amino acid soaps in the present composition is about 1% for about 0.001%-, and preferably about 0.01%-is about 0.2%, and most preferably from about 0.03%-about 0.12%.For topical ophthalmic, the concentration of fatty acid/acid/amino acid soaps should be not high to causing serious discomfort.
The present composition comprises cationic antibacterial agent and anionic polyelectrolyte.Cationic antibacterial agent comprises quaternary ammonium compound, as Benasept and Onamer M (polyquaternium-1).Anionic polyelectrolyte comprises that high molecular weight anionic plan mucosa (mucomimetic) polymer is (as carboxy vinyl polymer, as Carbopol ), polystyrolsulfon acid polymer, cation exchange resin (Amberlite for example Or Dowex ) etc.
The molecular weight that high molecular weight anionic is intended the mucosa polymer is about 50,000-6,000,000.These polymer are characterised in that to have the carboxylic-acid functional base and each functional group is preferably contained 2-7 carbon atom.Proper polymer amount anionic polymer is a carboxy vinyl polymer, preferably is called those of Carbomer, as Carbopol (B.F.Goodrich Co., Cleveland, Ohio).Preferred especially Carbopol 934P, Carbopol 974P and Carbopol 940.Other proper polymer amount anionic polymers comprise: alginate, carrageenin, natural gum (xanthan gum, karaya and tragacanth gum) and carboxymethyl cellulose.This base polymer uses with the amount of about 0.05%-about 6% usually, depends on desired composition viscosity.Transfusible fluid composition comprises this polymer of about 0.05%-about 2% usually.
Cation exchange resin is characterised in that highly acid, as has sulfonic acid or sulphuric acid degree of functionality those, or faintly acid, as has carboxylic functionality those.This resinoid is easy to from for example Rohm ﹠amp; (Philadelphia is Pennsylvania) with title Amberlite for Haas With (Midland is Michigen) with title Dowex from Dow Chemical Co. Buy.The particle mean size of these commercial resins is about 40-150 micron.But the granularity of this resin is vital to the ophthalmic composition of topical.Therefore, but for the ophthalmic composition of topical, the commercial resins granule is reduced to about 20 microns or lower granularity by known technology such as ball milling, so that particle mean size is smaller or equal to 10 microns, and preferably reduces to about 10 microns or lower granularity.Ion exchange resin uses with the amount of about 0.05%-about 10% usually.
Anion plan mucosa polymer and cation exchange resin discuss in more detail in 911,920 (mandates on March 27 nineteen ninety) at US4, and its whole disclosure is hereby incorporated by reference.
The polystyrolsulfon acid polymer (and salt) that can be used in the present composition comprises following repetitive: wherein: W=H or CH 3With
It is about 10 that x=makes the molecular weight of polystyrolsulfon acid polymer, 000-1,600,000 integer.
In preferred formula I polystyrolsulfon acid polymer, W=H and molecular weight are about 500, and 000-about 1,000,000, preferred about 600,000.If be present in the present composition, the polystyrolsulfon acid polymer of formula I accounts for and is lower than approximately 8%, preferably is lower than about 5%.
But can be included in eye medication, dermatosis medication, ear medication or nose medication that one or more composition activity compositions in the present composition comprise all local applications.For example, this class eye medication includes, but is not limited to: Betimol, as beta blocker (as betaxolol and timolol), muscarine medicine (muscarinics) (as pilocarpine), prostaglandin, carbonic anhydrase inhibitors (as acetazolamide, methazolamide and ethoxyzolamide), dopaminergic agonist and antagonist, and alpha adrenergic receptor agonists is as to amino clonidine (being also referred to as Apraclonidine) and brimonidine tartrate; Anti-infective is as ciprofloxacin; Non-steroid class and steroidal anti-inflammatory drugs are as suprofen, ketorolac, dexamethasone, rimexolone and Tetrahydrocortisol; Protein; Somatomedin is as EGF; And antiallergic agent, as disodium cromoglycate, Daren and Ao Luopatating (olopatadine).The present composition also can comprise the combination of active component.But the ophthalmic composition of topical most preferably.
The present composition also can comprise other components, as pharmaceutically acceptable buffer agent; Reinforcing agent (tonicity agent); Comfortable Booster; Add soluble additive; The pH regulator agent; Antioxidant and stabilizing agent.Compositions also can contain extra antiseptic (with above-mentioned cationic preservative combination).To understand as those skilled in the art, compositions can variously be suitable for dosage form (comprising solution, suspension, emulsion and the gel) preparation of topical.
The following example is used to illustrate other each side of the present invention, but does not limit the scope of the invention.
Embodiment 1
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Amberlite?IRP-69???????????????????0.25
Carbopol?974P??????????????????????0.45
AMINOSOAP LYC-12 *0.03
Boric acid 0.4
Mannitol 4.5
Disodiumedetate 0.01
Benasept 0.01
NaOH and/or HCl are in right amount to pH6.5
Pure water is in right amount to 100
*Aminosoap LYC-12 preparation:
0.42g betaxolol hydrochloride, 0.375gAmberlite IRP69 resin, 0.60g boric acid, 6.75g mannitol, 0.015gEDTA disodium are mixed in 40ml water and stirred 30 minutes.To 30% solution that wherein adds 1.06g1%BAC liquid storage, 33.8g2%Carbopol 974P oleo stock and 0.15g Cortex cocois radicis acyl-lysine (available from the Aminosoap LYC-12 of Ajinomoto).By adding the 2.2ml5N sodium hydroxide pH is transferred to 6.5 and add entry to make final inventory be 150ml.In the high pressure baking oven, preparation was sterilized 60 minutes in 121 ℃.
Embodiment 2
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Amberlite?IRP-69????????????????????0.25
Carbopol?974P???????????????????????0.45
AMINOSOAP LYC-12 *0.03
Boric acid 0.4
Mannitol 4.5
Disodiumedetate 0.01
Benasept 0.01+10%xs
Tromethane is in right amount to pH6.5
Pure water is in right amount to 100
*Aminosoap LYC-12 preparation:
0.84g betaxolol hydrochloride and 0.75gAmberlite IRP69 resin are mixed in about 30ml water and stirred 30 minutes.To wherein (with shown in order) add 67.5g2%Carbopol974P oleo stock, 13.5g mannitol, 0.03gEDTA disodium, 1.20g boric acid and 2.97g1.11% Benasept liquid storage.To wherein adding 25ml10% tromethane solution and mixture being stirred 2 hours.Add entry and make preparation reach 260g, and by dripping 10% tromethane solution with pH regulator to 6.0.30% solution that in preparation, adds 0.3g Cortex cocois radicis acyl-lysine (available from the Aminosoap LYC-12 of Ajinomoto).By dripping 10% tromethane solution pH is transferred to 6.5 and add entry to make final inventory be 300g.In the high pressure baking oven in 121 ℃ to preparation steam sterilization 60 minutes.
The preparation of finding embodiment 2 has following properties.
% labelling (label) Benasept 110% (be prepared into and contain excessive 10%)
% is combined chloride zephiran 0.76% not
% labelling betaxolol 100%
% is not in conjunction with betaxolol 28%
Mole osmotic pressure (osmolality) 312mOsm/Kg
Viscosity 138cps
Embodiment 3
Representative formulations
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Amberlite?IRP-69???????????????????0.25
Carbopol?974P??????????????????????0.45
AMINOSOAP LYC-12 *0.06
Boric acid 0.4
Mannitol 4.5
Disodiumedetate 0.01
Benasept 0.01
NaOH and/or HCl are in right amount to pH7.2
Pure water is in right amount to 100
*Aminosoap?LYC-12
Embodiment 4
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Amberlite?IRP-69???????????????????0.25
Carbopol?974P??????????????????????0.45
AMINOSOAP AR-12 *0.03
Boric acid 0.4
Mannitol 4.15
Disodiumedetate 0.01
Benasept 0.01+10%xs
Tromethane is in right amount to pH6.5
Pure water is in right amount to 100
*Aminosoap?AR-12
Embodiment 5
Representative formulations
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Brinzolamide???????????????????????1
Amberlite?IRP-69???????????????????0.25
Carbopol?974P??????????????????????0.45
Boric acid 0.4
Mannitol 4.5
AMINOSOAP LYC-12 *0.06
Disodiumedetate 0.01
Benasept 0.01
NaOH and/or HCl are in right amount to pH6.5
Pure water is in right amount to 100
*Aminosoap?LYC-12
Comparative Examples 1
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Amberlite?IRP-69???????????????????0.25
Carbopol?974P??????????????????????0.45
Boric acid 0.4
Mannitol 4.5
Disodiumedetate 0.01
Benasept 0.01
NaOH and/or HCl are in right amount to pH6.5
Pure water is in right amount to 100
Comparative Examples 2
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Benasept 0.01
Carbopol?974P??????????????????????0.45
Amberlite?IRP-69???????????????????0.25
Triethanolamine Cortex cocois radicis acyl glutamate *0.03
Boric acid 0.4
Mannitol 4.5
Disodiumedetate 0.01
NaOH and/or HCl are in right amount to pH6.5
Pure water is in right amount to 100
*Amisoft?CT-12
Comparative Examples 3
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Benasept 0.01+10%xs
Sodium lauroyl glutamate *0.03
Carbopol?974P??????????????????????0.45
Amberlite?IRP-69???????????????????0.25
Boric acid 0.4
Mannitol 4.15
Disodiumedetate 0.01
Tromethane is in right amount to pH6.5
Pure water is in right amount to 100
*Amisoft?LS-11
Comparative Examples 4
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Benasept 0.01+10%xs
The myristoyl sodium glutamate *0.03
Carbopol?974P??????????????????????0.45
Amberlite?IRP-69???????????????????0.25
Boric acid 0.4
Mannitol 4.15
Disodiumedetate 0.01
Tromethane is in right amount to 6.5
Pure water is in right amount to 100
*Amisoft?MS-11
Comparative Examples 5
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Benasept 0.01+10%xs
The stearyl sodium glutamate *0.03
Carbopol?974P??????????????????????0.45
Amberlite?IRP-69???????????????????0.25
Boric acid 0.4
Mannitol 4.15
Disodiumedetate 0.01
Tromethane is in right amount to pH6.5
Pure water is in right amount to 100
*Amisoft?HS-11
Comparative Examples 6
Constituent concentration (%)
Betaxolol hydrochloride 0.28
Benasept 0.01+10%xs
Carbopol?974P??????????????????????0.45
Triethanolamine Cortex cocois radicis acyl glutamate *0.03
Amberlite?IRP-69???????????????????0.25
Boric acid 0.4
Mannitol 4.5
Disodiumedetate 0.01
Tromethane is in right amount to pH6.5
Pure water is in right amount to 100
*Amisoft?CT-12
Comparative Examples 7
Constituent concentration (%)
Benasept 0.01
Mannitol 5
Pure water is in right amount to 100
Comparative Examples 8
Constituent concentration (%)
Benasept 0.01
Boric acid 0.4
Mannitol 4.9
Tromethane 0.726
Disodiumedetate 0.01
Pure water is in right amount to 100
Embodiment 6
Use organism to infect the antibiotic antiseptic effect of test determination according to the method described in American Pharmacopeia (USP) and the European Pharmacopoeia (Ph.Eur.).One or more following organism inoculation samples with known level: Gram-positive (staphylococcus aureus (Staphylococcus aureus) ATCC6538) and Gram-negative (Pseudomonas aeruginosa ATCC9027 and escherichia coli (Escherichia coli) ATCC8739) nutrition (vegetative) antibacterial, yeast (candida albicans (Candida albicans) ATCC10231) and mycete (aspergillus niger (Aspergillun niger) ATCC16404).Cultivate (pull) sample to determine whether antibiotic protective system can kill or suppress to introduce intentionally the organic propagation in the prescription with specific interval then.Press USP and/or Ph.Eur. preservative efficacy standards and measure the antibacterial activity level of ophthalmic preparation.
The concise and to the point antiseptic standard of ophthalmic preparation is as follows:
For antibacterial:
The logarithm (Log) of organism propagation reduces
Incubation time ????USP Ph.Eur. A (target) ??Ph.Eur. ??B(Min)
6 hours ????- ????2 ????-
24 hours ????- ????3 ????1
7 days ????- ????- ????3
14 days ????3 ????- ????-
28 days ????NI ????NR ????NI
For fungus:
Incubation time ????USP Ph.Eur. A (target) ??Ph.Eur. ??B(Min)
7 days ????- ????2 ????-
14 days ????NI ????- ????1
28 days ????NI ????NI ????NI
NR=is not recovered to organism
NI=maybe should cultivate the back when this is cultivated do not have increase
-=failed call when this is cultivated
The results are shown in following table 1 and 2 of microbial infection test.
Table 1:
The antiseptic effect standard
Prescription ????USP Ph.Eur. B (minimum) Ph.Eur. A (target)
Embodiment 1 * Qualified Qualified Defective
Embodiment 2 Qualified Qualified Defective
Embodiment 4 * Qualified Qualified Defective
Comparative Examples 1 Qualified Defective Defective
*Based on S.aureus, P.aeruginosa and A.niger data computing result
Table 2:
Organism (result-logarithm reduced in 7 days)
Prescription ?S.aureus ?P.aeruginosa ?E.coli ?C.albicans ??A.niger
Comparative Examples 2 ????2.9 ????5.0 ??-- ??????-- ????1.3
Comparative Examples 3 ????0.0 ????5.0 ??-- ??????-- ????2.9
Comparative Examples 4 ????1.5 ????5.0 ??-- ??????-- ????3.5
Comparative Examples 5 ????2.1 ????5.0 ??-- ??????-- ????3.6
Comparative Examples 6 ????0.5 ????5.0 ??5.0 ??????1.6 ????2.0
Comparative Examples 7 ????4.8 ????4.7 ??4.9 ??????4.7 ????2.5
Comparative Examples 8 ????4.8 ????4.7 ??4.9 ??????4.7 ????3.7
Its wideer aspect, above the present invention is not limited to shown in and described detail.Do not deviating from the principle of the invention and do not sacrificing under the situation of its advantage and can the scope of appended book changed.

Claims (19)

1. but the method for the antibacterial efficacy of the pharmaceutical composition of improvement or raising topical, this pharmaceutical composition comprises cationic antibacterial agent, anionic polyelectrolyte and active component, wherein this method comprises the fatty acid/acid/amino acid soaps that adds the antibiotic amount of raising in said composition, and described soap class has the C of being derived from 8-C 24The fatty acid component of fatty acid and be selected from lysine and arginic amino acid composition.
2. the process of claim 1 wherein that fatty acid component is selected from Cortex cocois radicis acyl group, inferior oleoyl, lauroyl, myristoyl, stearyl, oleoyl and pelargonyl group fatty acid residue.
3. the method for claim 2, wherein fatty acid component is the Cortex cocois radicis acyl group.
4. the process of claim 1 wherein that the antibiotic amount of raising of fatty acid/acid/amino acid soaps is about 0.001%-about 1%.
5. the method for claim 4, wherein the antibiotic amount of the raising of fatty acid/acid/amino acid soaps is about 0.01%-about 0.2%.
6. the method for claim 5, wherein the antibiotic amount of the raising of fatty acid/acid/amino acid soaps is about 0.03%-about 0.12%.
7. the process of claim 1 wherein that anionic polyelectrolyte is selected from carboxy vinyl polymer; Xanthan gum; The polystyrolsulfon acid polymer; And cation exchange resin.
8. the process of claim 1 wherein that but the pharmaceutical composition of topical further comprises one or more and is selected from a medication; The dermatosis medication; The active component of ear medication and nose medication.
9. the method for claim 8, but wherein the pharmaceutical composition of topical comprises and is selected from Betimol; Anti-infective; Non-steroid class and steroidal anti-inflammatory drugs; Protein; Somatomedin; Eye medication with antiallergic agent.
10. the method for claim 8, but wherein the pharmaceutical composition of topical further comprises one or more and is selected from pharmaceutically acceptable buffer agent; Reinforcing agent; Comfortable Booster; Add soluble additive; The pH regulator agent; The composition of antioxidant and stabilizing agent.
11. but the pharmaceutical composition of the topical of a fatty acid/acid/amino acid soaps that comprises cationic antibacterial agent, anionic polyelectrolyte, active component and the antibiotic amount of raising, described soap class has the C of being derived from 8-C 24The fatty acid component of fatty acid and be selected from lysine and arginic amino acid composition.
12. the compositions of claim 11, wherein fatty acid component is selected from Cortex cocois radicis acyl group, inferior oleoyl, lauroyl, myristoyl, stearyl, oleoyl and pelargonyl group fatty acid residue.
13. the compositions of claim 12, wherein fatty acid component is the Cortex cocois radicis acyl group.
14. the method for claim 11, wherein the antibiotic amount of the raising of fatty acid/acid/amino acid soaps is about 0.001%-about 1%.
15. the method for claim 14, wherein the antibiotic amount of the raising of fatty acid/acid/amino acid soaps is about 0.01%-about 0.2%.
16. the method for claim 15, wherein the antibiotic amount of the raising of fatty acid/acid/amino acid soaps is about 0.03%-about 0.12%.
17. the method for claim 11, wherein anionic polyelectrolyte is selected from carboxy vinyl polymer; Xanthan gum; The polystyrolsulfon acid polymer; And cation exchange resin.
18. the method for claim 11, but wherein the pharmaceutical composition of topical comprises and is selected from Betimol; Anti-infective; Non-steroid class and steroidal anti-inflammatory drugs; Protein; Somatomedin; Eye medication with antiallergic agent.
19. the method for claim 11, but wherein the pharmaceutical composition of topical further comprises one or more and is selected from pharmaceutically acceptable buffer agent; Reinforcing agent; Comfortable Booster; Add soluble additive; The pH regulator agent; The composition of antioxidant and stabilizing agent.
CN00813117A 1999-09-21 2000-09-11 Use of fatty acid/amino acid soaps to enhance antimicrobial effectiveness of topical pharmaceutical compositions Pending CN1374874A (en)

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US39901399A 1999-09-21 1999-09-21
US09/399,013 1999-09-21

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CN1374874A true CN1374874A (en) 2002-10-16

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CN101175474B (en) * 2005-03-10 2011-09-07 3M创新有限公司 Methods of reducing microbial contamination

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US6444710B1 (en) 1998-10-27 2002-09-03 Alcon Manufacturing, Ltd. Use of certain fatty acid/amino acid soaps to enhance antimicrobial effectiveness of topically administrable pharmaceutical compositions
TWI231759B (en) 2001-06-27 2005-05-01 Alcon Inc Olopatadine formulations for topical administration
US7977376B2 (en) 2001-06-27 2011-07-12 Novartis Ag Olopatadine formulations for topical nasal administration
FR2837710B1 (en) * 2002-03-26 2005-07-08 Innovations Pharma Ag TOPICAL COMPOSITION BASED ON ION-EXCHANGE RESINS, IN PARTICULAR FOR THE TREATMENT OF ERYTHEMES
US20130149394A1 (en) * 2010-08-27 2013-06-13 Wakamoto Pharmaceutical Co., Ltd. Aqueous ophthalmic composition

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DE4209722C3 (en) * 1992-03-25 1997-06-19 Medproject Pharma Entwicklungs Dripable gel for ophthalmology
US5520920A (en) * 1992-08-28 1996-05-28 Alcon Laboratories, Inc. Use of certain anionic surfactants to enhance antimicrobial effectiveness of ophthalmic compositions
US5504113A (en) * 1994-03-02 1996-04-02 Allergan, Inc. Enhancement of benzalkonium chloride preservative activity in formulations containing an incompatible drug
JPH0977725A (en) * 1995-09-13 1997-03-25 Ajinomoto Co Inc Production of lysine salt of fatty acid
CA2340225A1 (en) * 1998-10-27 2000-05-04 Wesley Wehsin Han Preservative system for topically administrable pharmaceutical compositions containing a fatty acid/amino acid soap

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101175474B (en) * 2005-03-10 2011-09-07 3M创新有限公司 Methods of reducing microbial contamination

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AU7363700A (en) 2001-04-24
BR0014117A (en) 2002-05-14
EP1214094A1 (en) 2002-06-19
TR200200724T2 (en) 2002-06-21

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