CN1257432A - Preservation composition containing tea tree oil (TTO) - Google Patents

Preservation composition containing tea tree oil (TTO) Download PDF

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Publication number
CN1257432A
CN1257432A CN98805398A CN98805398A CN1257432A CN 1257432 A CN1257432 A CN 1257432A CN 98805398 A CN98805398 A CN 98805398A CN 98805398 A CN98805398 A CN 98805398A CN 1257432 A CN1257432 A CN 1257432A
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alcohol
days
antiseptic
tto
phenyl
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约翰·亚历山大·斯塔顿
詹姆斯·史蒂文·罗
唐纳德·查尔斯·普里斯特
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MAINSTAR ONE INVESTMENTS Pty Ltd
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MAINSTAR ONE INVESTMENTS Pty Ltd
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N65/00Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N65/00Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08Magnoliopsida [dicotyledons]
    • A01N65/28Myrtaceae [Myrtle family], e.g. teatree or clove
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/61Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/63Oleaceae (Olive family), e.g. jasmine, lilac or ash tree

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
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  • Botany (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Alternative & Traditional Medicine (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Agronomy & Crop Science (AREA)
  • Plant Pathology (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Cosmetics (AREA)

Abstract

A preservative composition including: (i) 0.10-2.0 % tea tree oil; (ii) 0.10-2.0 % phenyl substituted alcohol; and (iii) one or more solvents for the tea tree oil and the phenyl substituted alcohol. A preservative concentrate comprising: (i) 20-80 % tea tree oil; (ii) 20-80 % phenyl substituted alcohol; (iii) 0-80 % surfactant; and (iv) 0-80 % dispersing agent.

Description

The antiseptic composition that contains tea tree oil (TTO)
Invention field
The present invention relates to a kind of modified model antiseptic composition that contains tea tree oil, it can use in family, industry or the agricultural products of wide region, comprises personal-care supplies, cosmetics, medicine, disinfectant, cleaning formulation, paint and other product that comprises the rotten in order to the inhibition microorganism of anticorrosion or antimicrobial or breed.
The present invention also provides and can mix in vehicle or the solvent to form the antiseptic concentrate of family, industry or agriculture articles for use.
Background of invention
The tea tree oil (TTO) that obtains by distillation altemifolia Cortex Melaleucae leucadendrae (Melaleuca alternifolia) is a kind of known natural antiseptic agent or has anti-microbial properties.For example, document " Carson etc., 1996, J.Antimicrob.Chemother.37 (6) B 1177-1179 " shows, as TTO during as the partly sterilised agent of wound, it is effective to streptococcus.Another piece document " Raman etc.; 1995; Lett.Appl.Microbiol.21 (4) 242-5 " has been described the purposes of TTO and its main component terpinene-4-alcohol (terpinene-4-ol), α-terpinol and australene, as shows the antibacterial activity to staphylococcus aureus (Staphylococcus aureus), staphylococcus epidermidis (Staphylococcusepidermidis) and propionibacterium acnes (Propionibacterium acnes).
Document " Carson etc., 1995, J.Appl.Bacteriol.78 (3) 264-9 " points out that TTO becomes a kind of welcome natural antimicrobial agent just day by day.Point out also that in the document terpinene-4-alcohol, coriandrol and α-terpinol also can be used for this field.Document " Shapiro etc., 1994, Oral Microbiol.Immunol.9 (4) 202-208 " points out that also TTO has accurately and the selectivity antibacterial activity the anaerobism oral cavity bacterium.
Australian Patent 559001 relates to a kind of TTO of comprising, has the polyvinyl of carboxyl and the protective skin cream of alcohol or glycol, and it can be used for the local application of skin injury.
Document " Proserpio etc., 1996, Cosmet.Toiletries, Ed.Ital.17 (3) 11-13,16-19 " has pointed out that also TTO has antimicrobial acivity in cosmetics, thereby can be used as antiseptic.
The document (Don Priest) that is entitled as " natural anticorrosion (Preserving naturally with tea treeoil) that adopts tea tree oil " is disclosed in In-Cosmetics Exhib.Conf.Proc., 1995,405-411.The document clearly illustrates that Melaleuca alternifolia is a kind of Australian Myrtaceae kind (Myrtaceae species) plant that originates in, and in iso standard 4730, it also is referred to as " oil of Cortex Melaleucae leucadendrae, terpinene-4-alcohol type " sometimes.
Tea tree oil is made up of the mixture of monoterpene, sesquiterpene and terpenol.Separablely from tea tree oil go out to surpass 90 kinds of chemical constituents.The shown antimicrobial acivity that goes out of tea tree oil mainly is because terpinene-other composition of 4-alcohol then has the active of self or plays synergism.Iso standard shows minimum 30% pure and mild maximum 15% the eucalyptole of terpinene-4-.
At present, the cosmetics of selling on market, medicine and personal-care supplies have at least 0.5% TTO usually, certainly, some the time, pure products is also sold.These products adopt TTO and the solvent property with anti-microbial effect.The scope of cosmetics, medicine and personal-care supplies comprises medicated soap, liquid soap, deodorizer and anti-perspirant, shampoo and conditioner, toothpaste, collutory and skin care item, comprises hand cream, sunscreen cream and acne preparation.
TTO also can be clarifying aqueous solution supply with, it comprises non-ionic surface active agent, is called polysorbas20 as polysorbate (Polysorbate) 20 or in above-mentioned Priest document and as the disodiumedetate (disodium edatate) of chelating agen.The document also discloses that the hair conditioning agent formulation, its comprise wheat protein aminoacid, for the pantothenylol of trophic factors, vitamin E, PEG-7 glyceryl cocoate (glyceryl cocoate) or as the Cetiol of stabilizing agent, as Derma-Guard polydimethylsiloxane, citric acid, vitamin A palmitate, as the butanediol of wetting agent, as the cetostearyl alcohol (cetosteary alcohol) of emulsifying agent, as the hexadecanol of emulsifying modifier and as the hexadecyltrimethylammonium chloride of antiseptic.The document is also pointed out, when TTO was used in the moisturiser (moisturising cream), moisturiser also can comprise herbaceous plant blend, hydrolytic collagen, propylene glycol, butanediol, vitamin E, vitamin A palmitate, olive oil, simmondsia oil, Macadamia nut oil, octyl palmitate and the cetearyl glucoside of hexadecanol, disodiumedetate, aloe vera gel, plant extract.
But, when in above-mentioned document, in various cosmetics and personal-care supplies, adopting TTO as natural antiseptic agent, its customary amount is 0.5%w/v, it may be noted that, in the Priest document, comprise in the preparation of TTO at some, the content of TTO can not pass through British Pharmacopoeia (BP) 1993 (adnexa XVI C) greater than 0.5%, and this pharmacopeia is the choice criteria to the preservative efficacy of medicine, cosmetics and personal-care supplies.Also with reference to American Pharmacopeia XXII, promptly USP XXII tests in the Priest document, and it also is that definite preservative efficacy is calibrated standard really.
Antiseptic such as TTO be used for preparation particularly aqueous compositions to prevent or the restriction micro-organisms infection development.This preparation can be any medicine, personal-care supplies or cosmetics.If antiseptic does not add in this product, microbial contamination might take place, thereby, to the harm that the user of product can bring secure context, perhaps can cause product rotten.The effect of anti-microbial preservative can be passed through medicine, personal-care supplies or cosmetic active ingredient, perhaps strengthens or weakens by the preparation of product or by container or the packing that is used for product.
Thereby, being necessary to show that the antimicrobial acivity that adds or do not add the product of antiseptic can provide suitable protection to illeffects, this effect can be embodied in duration of storage and product contamination by micro or propagation between the operating period.Therefore, this is the major function of BP and USP test.These two comprise: the inoculum with specified suitable microorganism is attacked corresponding preparations, under specified temperature the preparation of inoculation is preserved, and takes out sample with specified time interval, and to the microorganism count in the sample.
If under experimental condition at the appointed time with temperature after in the preparation inoculated microbial numbers significantly reduce or do not increase, then the antiseptic property of this preparation is suitable.Reduce in time according to micro organism quantity, acceptable standard will change with different preparation types.The test microorganism generally includes: black aspergillosis (Aspergillus niger) (ATCC 16404), Candida albicans (Candida albicans) (ATCC 10231), Pseudomonas aeruginosa (Pseudomonas aeruginosa) (ATCC 9027) and staphylococcus aureus (Staphylococcus aureus) (ATCC 6538).Be appreciated that the BP test is a kind of than the more strict test of USP test, for example, for topical formulations, it need have 3 logarithms to reduce by antibacterial after 48 hours, for oral formulations, had 3 logarithms to reduce in the time of 14 days; And, then require after 14 days number of bacteria to be reduced to and be no more than 0.1% of initial concentration for the USP standard.
With regard to the production of antiseptic, more extremely important is that the preparation of formation can be consistently by USP and the test of BP preservative efficacy.If can not pass through, then not only need elapsed time, and cost greatly changes the percentage composition of every kind of component in the compositions so that compositions can be tested by USP test and BP consistently, perhaps needs to add other conventional preservatives, as p-Hydroxybenzoate.For example, when the percentage ratio of the related component of compositions and concordance " are distorted " or changed and the compositions that obtains also can be had problems by BP and USP the time, described compositions may have deleterious effects aspect considering toxicity or safety and product stability the time, and this can increase the commercial risks and the security risk of selling this compositions significantly.
With regard to the TTO preparation of routine, if the content of TTO in preparation surpasses 2.0% then can be by BP and USP test.But, under many situations, consider the performance of TTO, because TTO is not only expensive, and has outstanding convergence and intensive abnormal flavour, it is too high that such concentration seems.
Summary of the invention
Thereby, the purpose of this invention is to provide the antiseptic composition of a kind of TTO of comprising, this antiseptic composition should be able to be consistently by the test of BP preservative efficacy, therefore, compares with above-mentioned prior art and to have multiple advantage.
Antiseptic composition of the present invention comprises pure and mild optionally at least 10% water and other component that the phenyl of TTO, the 0.10-2.0% of 0.10-2.0% replaces, these components can comprise the solvent of the alcohol that is used for TTO and phenyl replacement, comprise water and polar organic solvent, as ethanol, methanol, propylene glycol, butanediol, ethylene glycol or other polyhydroxyalkanes.The alcohol that phenyl replaces comprises phenyl and moieties, in this scope, comprises phenyl-paraffin alcohols and phenoxy group alkanol.The alcohol that phenyl replaces also is dissolved in the natural oil, as olive oil, simmondsia oil or Macadamia nut oil.The alcohol that preferred phenyl replaces comprises phenylethanol, phenyl phenol and benzyl alcohol.The preferred benzyl alcohol of the alcohol that the phenyl that the present invention adopts replaces.The preferred benzyl alcohol of the alcohol that replaces.
Be appreciated that if above-mentioned concentration range can be used, then in compositions of the present invention, can adopt the natural extract of the alcohol that comprises the phenyl replacement.
Said composition can be used as family, industry or agriculture articles for use by conventionally form, comprises that cosmetics, medicine, personal-care supplies, disinfectant, paint, cleaning formulation or other needs are anticorrosion or has antibacterial action to suppress the product that microorganism is rotten or breed.When as cosmetics or personal-care supplies, said composition for example can be cream, glue rod, varnish, foam, ointment, lotion (lotion) or spray.Compositions also can be included in conventional additive and the excipient that adopts in the topical formulations, as emulsifying agent, surfactant (comprising ion, nonionic and amphoteric surfactant), thickening agent, isostearyl glyceryl pentaerythrityl ether, stabilizing agent and wetting agent.
According to the present invention, the maximum level that preferred composition comprises the alcohol of TTO and phenyl replacement is 2.0%, and the concentration of the alcohol that TTO and phenyl replace is 1.0%.More preferably, the maximum level that compositions comprises the alcohol of TTO and phenyl replacement is 1.0%, and the concentration of the alcohol that TTO and phenyl replace is 0.5%.
Be appreciated that from industrial point of view medicine, personal-care supplies or cosmetic composition should comprise alap antiseptic according to cost and market acceptance level.For example, if TTO concentration is too high, then it will bring distinguished abnormal flavour and quite expensive.
Be appreciated that TTO can use its native form, and a kind of or various active component form is used with it, for example terpinene-4-alcohol and/or australene.Used herein term " tea tree oil " is meant the TTO of native form, it is to belong to (Leptosper-mum species) by any Melaleuca or Bao Zimu to obtain, for example, M. alternifolia, M.linariifolia, M.dessitafolia with and the modification extract, comprise above-mentioned active component itself.
Can use the benzyl alcohol that obtains by commercial sources, for example, the benzyl alcohol that the reaction of sodium carbonate or potassium carbonate and benzyl chloride is obtained.But, also can use the crude benzene methanol that obtains from suitable source, as jasmine, hyacinth or Cananga odorata oil.
Compositions of the present invention can be used as transparent aqueous solution, and except TTO and benzyl alcohol, it can comprise surfactant, emulsifying agent or the solubilizing agent of 1-20%.More preferably, can adopt non-ionic surface active agent, as polysorbate.Other suitable surfactant also is described below.
Except above-mentioned surfactant, compositions of the present invention can comprise 1-10% isostearyl glyceryl pentaerythrityl ether its skin is moisturized, more preferably, comprise the isostearyl glyceryl pentaerythrityl ether of 1-5%.Suitable isostearyl glyceryl pentaerythrityl ether is CETIOL or PEG7 coconut triglyceride.Also can comprise 1-10%, the wetting agent of preferred 1-5%, as thickening agent or the viscosifier of glycerol or propylene glycol and 1-5%, as colloid, for example guar gum, Tragacanth, xanthan gum or galactomannan gum.The detergent that also can comprise 1-15% is as sodium laureth sulfate and/or ammonium lauryl sulfate.Also can provide the cleaning agent of 1-5%, as the cocoyl diglycollic amide.
When as cream, compositions of the present invention can comprise wax, as spermol or the stearyl alcohol of 1-5%.
Also can comprise quintessence oil, medical herbs, vitamin, as vitamin E or vitamin A, hydrolytic collagen, aminoacid, pantothenylol and other required trophic factors.
Below list the example of the present composition when as transparent aqueous solution, transparency liquid soap, moisturiser, pearly shampoo and hair conditioner with collagen and Chinese herbal medicine extract.(A) transparent aqueous solution
0.5%TTO, 0.5% benzyl alcohol, 1.6-3.2% polysorbate 20 or other suitable non-ionic surface active agent, 0.1% disodiumedetate or other suitable chelating agen and 0-5.0% butanediol, surplus is a pure water.(B) transparency liquid soap
0.5%TTO, 0.5% benzyl alcohol, 10.0% sodium laureth sulfate 70.0% (EmpicolESB 70), 5.0% ammonium lauryl sulfate 30.0% (Empicol ALS 30), 0.05% disodiumedetate, 1.5% Cortex cocois radicis betanin (cocobetaine) (Empigen BB), 1.9% coconut oil diethanol amide (coconut diethanolamide) (Empilan FD), 0.20% sodium chloride, concentration be 10.0% citric acid solution so that pH is 6.7, surplus is a pure water.(C) contain the moisturiser of collagen and herb extracts
0.5%TTO, 0.5% benzyl alcohol, 5.0% octyl palmitate, 1.0% olive oil, 4.0% simmondsia oil, 1.0% Macadamia nut oil, 4.0%cetearyl glucoside (Montanol 68), 0.3% natural Vitamin E (Covitol F1300), 0.075% vitamin A palmitate, 2.0% butanediol, 5.0% propylene glycol, 1.0% hydrolytic collagen (Crotein A), 1.0% medical herbs blend (cer-nica, Althaea officinalis, Fructus Cucumidis sativi, Fols sambuci williamsii, the equivalent extract of hazel and Citrus aurantium Linn. flower), 10.0% aloe vera gel, 0.1% disodiumedetate, spice 0.35%, surplus is a pure water, and pH 5.1.(D) pearly shampoo
0.5%TTO, 0.5% benzyl alcohol, 10% sodium lauryl tri(oxyethyl) sulfate, 0.05% disodiumedetate, 3.0% Cortex cocois radicis betanin, 3.0% coconut oil diethanol amide (Empilan FD), 0.10% season hydroxyethyl-cellulose (Polyquatemium) 10 (Polymer JR400), 3.0% pearling agent (Euperlan PK771), 0.20% sodium chloride, citric acid (10.0%) use the purified water balance to pH6.5.(E) hair conditioner
0.5%TTO, 0.5% benzyl alcohol, 3.0% cetostearyl alcohol, 0.15% polydimethylsiloxane vitamin E natural product (Covitol F1300), 0.05%PEG-7 glyceryl cocoate (Cetiol HE), 1.0% wheat protein aminoacid (Hydrotriticum WAA), 0.10% citric acid (10.0%), 0.10% pantothenylol and 1.0% hexadecyltrimethylammonium chloride 50.0% (Dehyquart A), surplus is a purified water.
On the other hand, the invention provides a kind of antiseptic concentrate, it comprises:
(i)20-80%TTO;
The (ii) alcohol that replaces of 20-80% phenyl;
(iii) 0-80% surfactant; With
(iv) 0-80% dispersant.
Preferably in this concentrate, provide the surfactant of 25-80% and the dispersant of 20-80%.More preferably, provide the surfactant of 35-45% and the dispersant of 20-50%.
Preferred concentrate comprises the alcohol that the phenyl of the TTO of 30-50% and 30-50% replaces.More preferably, the alcohol that TTO and phenyl replace can exist by isoconcentration, and concentration separately for example is 40%.
Surfactant can be an anion surfactant, as: carboxylate, sulfonate, sulfated alcohols or sulfated alcohols ethoxylate.Also can adopt cationic surfactant and amphoteric surfactant, but preferred surfactants is a non-ionic surface active agent, as polyoxyethylene surfactant or carboxylate, as glyceride, polyoxyethylene ester, sorbitan esters, natural fat, oil and wax and ethoxylation and glyceride fatty acid.
Preferred surfactants is those commercial surfactant of trade (brand) name ETOCAS or CREMOPHOR.
The effect of dispersant is to be convenient to the dispersion of TTO in concentrate.If there is no dispersant then is necessary very lentamente the alcohol that TTO and water and the phenyl that needs concentrate to form gel replace is mixed together.Adopt dispersant that the clear solution of concentrate also can be provided.Preferred dispersing agent is a propylene glycol, it will be appreciated, of course, that any other polyhydroxy-alcohol all can adopt, as glycerol, sorbitol or Polyethylene Glycol.Other alcohol also can adopt, as methanol, ethanol or isopropyl alcohol.
The preferred form of concentrate is the aqueous solution form, and it comprises TTO, 0.5g benzyl alcohol, 1.0g surfactant and the 0.5g propylene glycol of 0.5g.In this optimal way, the 2.5g concentrate of formation is dissolvable in water in 100g vehicle or the diluent.
In another embodiment, concentrate comprises the TTO of 0.5g, 0.5g benzyl alcohol and 1.0g propylene glycol.In this embodiment, obtain the concentrate of 2.0g, it is dissolvable in water in 100g vehicle or the diluent.This concentrate can be used in non-water vehicle or the solvent.
An example of the concentrate of producing according to the present invention comprises Etocas 35 (being Polyoxyl 35 Oleum Ricini) and 20% propylene glycol as surfactant of 20% TTO, 20% benzyl alcohol, 35-40%.The Etocas of this TTO, 1.0g and 0.5g propylene glycol corresponding to 0.5g benzyl alcohol, 0.5g.This concentrate is used for following products: (F) general facial cream
10%Emulgade 1000 NI, it is the colloid dispersed mixture (in the satisfied fatty acid macrogol ester) of cetyl stearyl alcohol and nonionic emulsifier, 5% Oleum Arachidis hypogaeae semen, 2.5% glycerol and 2.5% antiseptic concentrate, surplus is a pure water.(G) general lotion (Lotion)
15% glyceryl monostearate A-S, 3%Emulgin B1 (, having about 12 moles oxirane), 5% glycerol, 2% hexadecanol as the cetyl stearyl alcohol of nonionic emulsifier, 2.5% antiseptic concentrate, surplus is a purified water.(H) general gel preparation
3%Sepigel 305 (the isoparaffin dispersion of polyacrylamide solution), 2.5% antiseptic concentrate, 5% glycerol, surplus is a purified water.(I) general conditioner
2% hexadecanol, 3% cetostearyl alcohol, 3% Vantoc CC (hexadecyltrimethylammonium chloride), 5% CroquotL 5% (lauryl di-ammonium salts hydroxypropyl hydrolytic collagen), DiPanthenol 0.5%, antiseptic concentrate 2.5%, surplus is a purified water.
The step of preparation conditioner comprises: with the mixture heated to 70 of hexadecanol and hexadecanol octadecanol ℃.Vantoc CC is dissolved in the water, and is heated to 70 ℃.Two kinds of solution are merged, will be cooled to 40 ℃, at this moment, add CroquotL and mixing.Mixture is cooled to 35 ℃,, DiPanthenol is mixed with the antiseptic concentrate.Then, conditioner is stirred until cooling.
Experiment
Measure the test test organism of BP preservative efficacy
(i) (ATCC 16404, IP for black aspergillosis (Aspergillus niger) IMI 149 007
1431.83);
(ii) (ATCC 10231, IP for Candida albicans (Candida albicans) NCPF 3179
48.72);
(iii) Pseudomonas aeruginosa (Pseudomonas aeruginosa) NCIMB 8626 (ATCC
9027,CIP?82.118);
(iv) staphylococcus aureus (Staphylococcus aureus) NCTC 10788
(NCIMB?9518,ATCC?6538,CIP?4.83)。The inoculum preparation
Before test, tryptose soya agar plate that is used for antibacterial or the Sabouraud agar plate that is used for fungus are inoculated with the new cultivation stock culture of each specified microorganisms.30-35 ℃ of following culture of bacteria culture fluid 18-24 hour, cultivated the Candida albicans culture fluid 48 hours down at 20-25 ℃, 20-25 ℃ of following black aspergillosis culture fluid 7 days until obtaining good Sporulation.Be in its optimum state after microorganism is bringing back to life before, may need the cultivation of going down to posterity, still, the number of cultivating of recommending to go down to posterity keeps minimum.
In order to obtain antibacterial and Candida albicans culture fluid, adopt the aseptic suspension of the peptone of the sodium chloride that comprises 0.9%w/v and 0.1%, be used for disperseing and the transitional surface growth-gen enters in the suitable container.Add competent suspension to reduce microbial numbers to about 10 8/ ml.Comprise the sodium chloride of 0.9%w/v and the aseptic suspension of 0.05% polysorbate 80 for obtaining black aspergillosis culture fluid, adopting, add identical solution and count up to about 10 to regulate spore 8/ ml.
By plate counting or by membrane filtration, from each suspension, discharge suitable sample immediately and the number of the every ml colony-forming units in every kind of suspension is measured.This value is used for determining the inoculum and the benchmark of in test use.Suspension should use immediately.Process of the test
For microorganism variable in postvaccinal product is counted, be used for the gelose medium of the initial cultivation of microorganism separately.
Each is inoculated the content of a series of detected products with a kind of suspension in the test organism, obtains in every g or the every ml preparation 10 5-10 6The inoculation number of individual microorganism.The suspension vol of inoculum is no more than 1% of small product size.Fully mix to guarantee uniform distribution.
Postvaccinal product is remained under 20-25 ℃ the lucifuge protection.According to the type of product, at zero hour with from each container, take out suitable sample during at suitable interval, be generally 1-ml or 1-g quantity, measure the number of survival microorganism by plate counting or membrane filtration.Guarantee by dilution, filter or adopt the specific remaining antimicrobial acivity of inactivator elimination product.When adopting dilution, stay surplus with agreement for reducing sensitivity when reclaiming a small amount of survival microorganism.When using specific inactivator, it is suitable to come the affirmation system to have the ability to support the growth of test organisms in the same old way to adopt.
The test of USP preservative efficacy is adopted with similar and relevant with the test of BP preservative efficacy as mentioned above process and is carried out.
But, BP and USP to accept standard different.In BP, for topical formulations, for inoculum 10 in every g or the every ml preparation 5-10 6Antibacterial, this preparation will pass through BP, and then they must demonstrate 3 logarithms minimizings in the time of 48 hours, do not have recovery in the time of 7,14 and 28 days.For topical formulations, for inoculum 10 in every g or the every ml preparation 5-10 6Fungus, this preparation will pass through BP, and then they must demonstrate 2 logarithms minimizings in the time of 14 days, do not have recovery in the time of 28 days.Above-mentioned standard (also being referred to as standard A) shows the recommendation effect that will reach.
And for oral formulations, for 10 5-10 6The inoculum of antibacterial, they must demonstrate, and 3 logarithms reduce in the time of 14 days, do not have recovery in the time of 28 days.For 10 5-10 6Fungal inocula, they must demonstrate, and 1 logarithm reduces in the time of 14 days, does not have recovery in the time of 28 days.
By comparison, for USP, preparation must demonstrate by USP: (i) for antibacterial, the minimizing value of growth is no more than 0.1% of initial concentration in the time of 14 days; (ii) for fungus, during 14 days, concentration must remain on initial concentration or be lower than initial concentration.Under these situations, must show equally, for remaining 28 days duration of test, the concentration of every kind of test organism must keep above-mentioned (i) and level (ii) or be lower than this level.
Therefore, from aforementioned content as can be seen, the BP test standard is more stricter than USP standard.
Embodiment
Embodiment 1
Following preparation is carried out the test relevant with BP and USP, and described preparation comprises 0.2% benzyl alcohol, 0.5%TTO, Etocas 35 1.0%, propylene glycol 0.5%, and all the other are water, the results are shown in table 1.This preparation can not can not pass through USP by BP.
Embodiment 2
Prepare similar preparation as process as described in the embodiment 1, just the concentration of benzyl alcohol increases to 0.5%.The results are shown in table 2, the result shows that this preparation can be by BP and USP.
Embodiment 3
Prepare similar preparation as process as described in the embodiment 1, just the concentration of TTO reduces to 0.3%.The results are shown in table 3, the result shows that this preparation can not can not pass through USP by BP.
Embodiment 4
Prepare similar preparation as process as described in the embodiment 1, just the concentration of benzyl alcohol increases to 0.5%, and the concentration of TTO reduces to 0.3%.The results are shown in table 4, the result shows that this preparation can be by BP and USP.
Embodiment 5
Prepare similar preparation as process as described in the embodiment 1, just economize and omit TTO, and the concentration of benzyl alcohol is 0.5%.The results are shown in table 5, the result shows that this preparation can not can not pass through USP by BP.
Embodiment 6
Prepare similar preparation as process as described in the embodiment 1, just economize and omit benzyl alcohol, and the concentration of TTO is 0.3%.The results are shown in table 6, the result shows that this preparation can not pass through BP for topical formulations.More particularly, the fungus counting did not reduce 10 in 14 days 2Doubly.
Embodiment 7
Prepare similar preparation as process as described in the embodiment 1, just economize and omit benzyl alcohol, and the concentration of TTO is 0.5%.The results are shown in table 7, the result shows that this preparation can not pass through BP for topical formulations, because black aspergillosis counting did not reduce 10 in 14 days 2Doubly.
Embodiment 8
Contain the aqueous solution of 0.3%TTO and the preparation of 1.0%Etocas 35 and carry out BP and USP test respectively.Table 8 is the result show, this preparation can not can not pass through USP by BP, and particularly, it does not have an activity to Pseudomonas aeruginosa and black aspergillosis.
Embodiment 9
Only with regard to following preparation carry out with corresponding to the relevant test of the aspergillar BP local standard of black, described preparation comprises 0.2% benzyl alcohol, 1%Etocas 35,0.5% propylene glycol, all the other are water, the results are shown in table 9.This preparation can not pass through BP.Also said preparation has only been carried out the results are shown in table 10 corresponding to the test of the aspergillar USP of black.Show that this preparation can not pass through USP.
Embodiment 10
The preparation of embodiment 9 is modified concentration to 0.5% with independent increase benzyl alcohol, only to preparation carry out with corresponding to the relevant test of the aspergillar BP of black.The result of table 11 shows, the aspergillar effectiveness of black is significantly improved, and therefore, this preparation can pass through BP.
Embodiment 11
Repeat embodiment 10 fully, and test, the results are shown in 12, show experimental result similar to Example 10 with the USP standard.
Embodiment 12
The preparation of embodiment 9 is modified having the concentration of 1.0% benzyl alcohol, and simultaneously to only testing corresponding to aspergillar BP local standard of black and USP standard.These the results are shown in table 13 and 14, and aspergillar growth has had strong inhibitory effects to black to show benzyl alcohol.
Embodiment 13
Carry out test to comprising 0.2% phenyl phenol, 0.5%TTO and 1.0%Etocas 35 and all the other for the preparation of water with respect to the standard of BP part and USP.These the results are shown in the table 15, and the result shows that these preparations can pass through the requirement of BP (standard A) and USP.
Embodiment 14
Prepare similar preparation as process as described in the embodiment 13, just the concentration of phenyl phenol increases to 0.5%.The results are shown in table 16, the result shows that this preparation has passed through BP (standard A) and USP.
Embodiment 15
Prepare similar preparation as process as described in the embodiment 13, just the concentration of TTO reduces to 0.3%.The results are shown in table 17, the result shows that this preparation satisfies the requirement of the aspergillar BP of black (standard B) being tested and satisfies USP.
Embodiment 16
Prepare similar preparation as process as described in the embodiment 13, just the concentration of phenyl phenol increases to 0.5%, and the concentration of TTO reduces to 0.3%.The results are shown in table 18, the result shows that this preparation satisfies the requirement of BP (standard A) and USP.
Embodiment 17
Prepare similar preparation as process as described in the embodiment 13, just the concentration of phenyl phenol increases to 0.5%, economizes and omits TTO.The results are shown in table 19, the result shows, this preparation can not be by the requirement of BP, but can be by the requirement of USP.
Embodiment 18
Prepare similar preparation as process as described in the embodiment 13, just the concentration of phenyl phenol increases to 1.0%, economizes and omits TTO.The results are shown in table 20, the result shows that this preparation satisfies the requirement of BP (standard A) and USP.
Embodiment 19
Prepare similar preparation as process as described in the embodiment 13, just the concentration of phenyl phenol increases to 0.5%, economizes and omits TTO and Etocas 35.The results are shown in table 21, the result shows that this preparation can not satisfy the requirement of BP, but can be by the requirement of USP.
Embodiment 20
Prepare similar preparation as process as described in the embodiment 13, just the concentration of phenyl phenol increases to 1.0%, economizes and omits TTO and Etocas 35.The results are shown in table 22, the result shows that this preparation satisfies the requirement of BP (standard A) and USP.
Embodiment 21
Carry out test to comprising 0.2% phenyl phenol, 0.5%TTO, 1.0%Etocas 35 and 0.5% propylene glycol and all the other for the preparation of water with respect to BP and USP.These the results are shown in the table 23, and the result shows, this preparation can not can not be by USP to the aspergillar requirement of black by BP.
Embodiment 22
Prepare similar preparation as process as described in the embodiment 21, just the concentration of phenyl phenol increases to 0.5%.The results are shown in table 24, the result shows that this preparation satisfies the requirement of BP and USP.
Embodiment 23
Prepare similar preparation as process as described in the embodiment 21, just the concentration of TTO reduces to 0.3%.The results are shown in table 25, the result shows, this preparation can not be by BP and USP to the aspergillar requirement of black.
Embodiment 24
Prepare similar preparation as process as described in the embodiment 21, just the concentration of phenyl phenol increases to 0.5%, and the concentration of TTO reduces to 0.3%.The results are shown in table 26, the result shows that this preparation can be by the requirement of BP and USP.
Embodiment 25
Prepare similar preparation as process as described in the embodiment 21, just the concentration of phenyl phenol increases to 0.5%, economizes and omits TTO.The results are shown in table 27, the result shows, this preparation can not can not be by the requirement of USP by BP.
Embodiment 26
Prepare similar preparation as process as described in the embodiment 21, just the concentration of phenyl phenol increases to 1.0%, economizes and omits TTO.The results are shown in table 28, the result shows that this preparation can be by the requirement of BP and USP.
Embodiment 27
Prepare similar preparation as process as described in the embodiment 21, just the concentration of phenyl phenol increases to 0.5%, economizes and omits TTO and Etocas 35.The results are shown in table 29, the result shows that this preparation can be by the requirement of BP and USP.
Embodiment 28
Prepare similar preparation as process as described in the embodiment 27, just the concentration of phenyl phenol increases to 1.0%.The results are shown in table 30, the result shows that this preparation can be by the requirement of BP and USP.
Conclusion
From the foregoing description as can be seen, the preferred antiseptic of compositions comprises at least 0.3% TTO and 0.5% benzyl alcohol.Can find out that also aspergillar growth has more inhibition to benzyl alcohol for black, TTO is to its then no effect relatively.On the other hand, TTO is then more effective to the antibacterial that comprises Pseudomonas aeruginosa, and benzyl alcohol is then to this antibacterial relative nullity.
Table table 1
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.0×10 6 ????1.4×10 7 ???1.1×10 7 ???1.3×10 6 ????1.1×10 6
0 hour ????5.4×10 6 ????>2.5×10 7 ?????- ???3.6×10 6 ????8.0×10 5
48 hours ????>2.5×10 4 ????<10 ?????- ???????- ???????-
7 days ????>2.5×10 4 ????<10 ????<10 ????<10 ????3.5×10 5
14 days Cancellation ????17/9/96 ????1.3×10 5
21 days
28 days
Table 2
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.0×10 6 ????1.4×10 7 ????1.1×10 7 ????1.3×10 6 ????1.1×10 6
0 hour ????2.6×10 6 ????1.7×10 7 ??????- ????3.4×10 6 ????6.0×10 5
48 hours ????<10 ????<10 ??????- ???????- ???????-
7 days ????<10 ????<10 ????<10 ????<10 ????3.0×10 4
14 days ????<10 ????<10 ????<10 ????<10 ????<10
21 days ????<10 ????<10 ????<10 ????<10 ????<10
28 days ????<10 ????<10 ????<10 ????<10 ????<10
Table 3
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.0×10 6 ????1.4×10 7 ????1.1×10 7 ????1.3×10 6 ????1.1×10 6
0 hour ????2.9×10 6 ????>2.5×10 7 ???????- ????2.0×10 6 ????1.4×10 5
48 hours ????<10 ????<10 ???????- ???????- ???????-
7 days ????<10 ????<10 ????<10 ????1.1×10 3 ????2.3×10 5
14 days Cancellation ????17/9/96 ????1.9×10 5
21 days
28 days
Table 4
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.0×10 6 ????1.4×10 7 ????1.1×10 7 ????1.3×10 6 ????1.1×10 6
0 hour ????2.8×10 6 ????>2.5×10 7 ???????- ????4.1×10 6 ????7.0×10 5
48 hours ????<10 ????<10 ???????- ??????- ???????-
7 days ????<10 ????<10 ????<10 ????<10 ????1.5×10 5
14 days ????<10 ????<10 ????<10 ????<10 ????10
21 days ????<10 ????<10 ????<10 ????<10 ????<10
28 days ????<10 ????<10 ????<10 ????<10 ????<10
Table 5
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ?????3.7×10 6 ?????4.6×10 6 ????4.5×10 6 ?????8.3×10 5 ?????6.0×10 5
0 hour ?????3.4×10 6 ?????9.9×10 6 ???????- ?????8.5×10 5 ?????4.0×10 5
48 hours ?????>2.5×10 4 ????>2.5×10 4 ???????- ????????- ???????-
7 days ?????5.0×10 5 ????<100 ????3.0×10 6 ?????1.8×10 5 ?????9.0×10 4
14 days ?????>2.5×10 4 ????<100 ????>2.5×10 4 ?????2.9×10 4 ?????1.5×10 4
21 days ?????>2.5×10 4 ????<100 ????>2.5×10 4 ?????5.3×10 2 ?????4.0×10 2
28 days ?????2.0×10 4 ????<100 ????2.2×10 4 ????<100 ?????2.0×10 2
Table 6 is all results represent with cfu/g
Density Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.1×10 6 ????7.6×10 6 ????2.9×10 7 ????6.0×10 5
0 hour ????3.4×10 6 ????7.6×10 5 ????2.5×10 7 ????1.8×10 6
48 hours ????7.8×10 2 ????<10 ??????- ??????-
7 days ????<10 ????<10 ??????- ??????-
14 days ????<10 ????<10 ????2.8×10 6 ????6.0×10 5
28 days ????<10 ????<10 ????1.3×10 6 ????7.0×10 4
Table 7 is all results represent with cfu/g
Density Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.1×10 6 ????7.6×10 6 ????2.9×10 7 ?????6.0×10 5
0 hour ????2.5×10 6 ????2.8×10 6 ????2.9×10 7 ?????2.6×10 5
48 hours ????<10 ????<10 ???????- ???????-
7 days ????<10 ????<10 ???????- ???????-
14 days ????<10 ????<10 ????7.8×10 2 ?????5.6×10 5
28 days ????<10 ????<10 ????9.0×10 1 ?????1.1×10 5
Table 8 is all results represent with cfu/g
Density Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????7.3×10 5 ????2.6×10 6 ????4.1×10 6 ????4.8×10 5 ????9.0×10 5
0 hour ????6.8×10 5 ????2.2×10 6 ??????- ????4.2×10 5 ????9.0×10 5
48 hours ????<10 ????9.5×10 4 ??????- ???????- ???????-
7 days ????<10 ????>2.5×10 5 ????<10 ?????<10 ????7.0×10 1
14 days ????<10 ????1.9×10 6 ????<10 ?????<10 ????2.0×10 5
Table 9 is all results represent with cfu/g
Density/g Black aspergillosis ATCC16404
Inoculum ???????2.2×10 5
7 days ???????2.6×10 5
14 days ???????2.0×10 5
21 days ???????1.6×10 5
Table 10 is all results represent with cfu/g
Density/g Black aspergillosis ATCC16404
Inoculum ???????2.2×10 5
7 days ???????2.6×10 5
14 days ???????1.6×10 5
Table 11 is all results represent with cfu/g
Density/g Black aspergillosis ATCC16404
Inoculum ?????2.2×10 5
7 days ?????1.1×10 5
14 days ?????3.2×10 5
21 days ?????4.0×10 2
28 days Less than 100
Table 12 is all results represent with cfu/g
Density/g Black aspergillosis ATCC16404
Inoculum ????????2.2×10 5
0 hour ????????2.2×10 5
14 days ????????3.2×10 5
28 days Less than 100
Table 13 is all results represent with cfu/g
Density/g Black aspergillosis ATCC16404
Inoculum ?????????2.2×10 5
0 hour ?????????3.2×10 5
14 days Less than 100
28 days Less than 100
Table 14 is all results represent with cfu/g
Density/g Black aspergillosis ATCC16404
Inoculum ??????2.2×10 5
7 days Less than 100
14 days Less than 100
21 days Less than 100
28 days Less than 100
Table 15
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ???1.6×10 6 ????8.2×10 5 ????2.9×10 6 ????7.7×10 5 ????1.8×10 5
0 hour ???4.8×10 5 ????2.7×10 5 ???????- ????<100 ????3.0×10 4
48 hours ???<100 ????<100 ???????- ???????- ???????-
7 days ???<100 ????<100 ????<100 ????<100 ????3.8×10 3
14 days ???<100 ????<100 ????<100 ????<100 ????3.6×10 3
21 days ???<100 ????<100 ????<100 ????<100 ????3.0×10 3
28 days ???<100 ????<100 ????<100 ????<100 ????1.5×10 3
Table 16
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ???????1.6×10 6 ????8.2×10 5 ????2.9×10 6 ????7.7×10 5 ????1.8×10 5
0 hour ???????5.5×10 5 ????8.9×10 4 ??????- ????<100 ????7.0×10 4
48 hours ???????<100 ????<100 ??????- ??????- ??????-
7 days ???????<100 ????<100 ????<100 ????<100 ????3.0×10 2
14 days ???????<100 ????<100 ????<100 ????<100 ????<100
21 days ???????<100 ????<100 ????<100 ????<100 ????<100
28 days ???????<100 ????<100 ????<100 ????<100 ????<100
Table 17
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????1.6×10 6 ????8.2×10 5 ????2.9×10 6 ????7.7×10 5 ????1.8×10 5
0 hour ????8.9×10 5 ????3.2×10 5 ???????- ????6.2×10 5 ????1.2×10 5
48 hours ????<100 ????<100 ???????- ???????- ???????-
7 days ????<100 ????<100 ????<100 ????<100 ????1.2×10 4
14 days ????<100 ????<100 ????<100 ????<100 ????7.2×10 3
21 days ????<100 ????<100 ????<100 ????<100 ????6.5×10 3
28 days ????<100 ????<100 ????<100 ????<100 ????2.3×10 3
Table 18
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC016404
Inoculum ????1.6×10 6 ????8.2×10 5 ????2.9×10 6 ????7.7×10 5 ????1.8×10 5
0 hour ????7.8×10 5 ????7.6×10 4 ????????- ????4.6×10 4 ????6.0×10 4
48 hours ????<100 ????<100 ????????- ??????- ???????-
7 days ????<100 ????<100 ????<100 ????<100 ????2.0×10 3
14 days ????<100 ????<100 ????<100 ????<100 ????2.0×10 2
21 days ????<100 ????<100 ????<100 ????<100 ????<100
28 days ????<100 ????<100 ????<100 ????<100 ????<100
Table 19
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????1.6×10 6 ????8.2×10 5 ????2.9×10 6 ????7.7×10 5 ????1.8×10 5
0 hour ????5.4×10 5 ????4.0×10 5 ??????- ????5.7×10 3 ????1.4×10 5
48 hours ????3.9×10 4 ????7.9×10 4 ??????- ???????- ???????-
7 days ????<100 ????<100 ????<100 ????2.0×10 4 ????3.9×10 3
14 days ????7.0×10 3 ????<100 ????<100 ????5.3×10 4 ????2.9×10 3
21 days ????<100 ????<100 ????<100 ????4.6×10 3 ????1.2×10 3
28 days ????<100 ????<100 ????<100 ????5.0×10 2 ????2.5×10 2
Table 20
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????1.6×10 6 ????8.2×10 5 ????2.9×10 6 ????7.7×10 5 ????1.8×10 5
0 hour ????6.4×10 5 ????2.9×10 5 ??????- ????9.4×10 4 ????5.0×10 4
48 hours ????3.5×10 4 ????<100 ??????- ??????- ??????-
7 days ????<100 ????<100 ????<100 ????<100 ????<100
14 days ????<100 ????<100 ????<100 ????<100 ????<100
21 days ????<100 ????<100 ????<100 ????<100 ????<100
28 days ????<100 ????<100 ????<100 ????<100 ????<100
Table 21
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????1.6×10 6 ????8.2×10 5 ????2.9×10 6 ????7.7×10 5 ????1.8×10 5
0 hour ????7.6×10 5 ????5.6×10 5 ??????- ????5.8×10 5 ????7.0×10 4
48 hours ????5.0×10 4 ????8.5×10 3 ??????- ???????- ???????-
7 days ????<100 ????<100 ????<100 ????1.2×10 5 ????1.4×10 3
14 days ????5.3×10 3 ????<100 ????<100 ????1.5×10 4 ????3.0×10 3
21 days ????4.5×10 2 ????<100 ????<100 ????2.4×10 3 ????1.1×10 3
28 days ????4.5×10 2 ????<100 ????<100 ????1.0×10 2 ????<100
Table 22
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ???1.6×10 6 ????8.2×10 5 ????2.9×10 6 ????7.7×10 5 ????1.8×10 5
0 hour ???5.0×10 5 ????2.9×10 5 ???????- ????2.9×10 5 ????9.0×10 4
48 hours ???<100 ????<100 ???????- ??????- ??????-
7 days ???<100 ????<100 ????<100 ????<100 ????<100
14 days ???<100 ????<100 ????<100 ????<100 ????<100
21 days ???<100 ????<100 ????<100 ????<100 ????<100
28 days ???<100 ????<100 ????<100 ????<100 ????<100
Table 23
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.2×10 6 ????2.9×10 6 ???7.8×10 6 ????5.5×10 6 ????7.2×10 5
0 hour ????2.4×10 5 ????3.2×10 4 ??????- ????1.1×10 6 ????9.8×10 4
48 hours ????<100 ????<100 ??????- ??????- ???????-
7 days ????<100 ????<100 ????<100 ????<100 ????1.1×10 4
14 days ????<100 ????<100 ????<100 ????<100 ????3.1×10 4
21 days ????<100 ????<100 ????<100 ????<100 ????1.6×10 4
28 days ????<100 ????<100 ????<100 ????<100 ????4.2×10 4
Table 24
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.2×10 6 ???2.9×10 6 ????7.8×10 6 ????5.5×10 6 ????7.2×10 5
0 hour ????7.5×10 5 ???5.2×10 5 ??????- ????2.1×10 5 ????8.2×10 4
48 hours ????<100 ???<100 ??????- ??????- ??????-
7 days ????<100 ???<100 ????<100 ????<100 ????7.8×10 3
14 days ????<100 ???<100 ????<100 ????<100 ????1.1×10 3
21 days ????<100 ???<100 ????<100 ????<100 ????<100
28 days ????<100 ???<100 ????<100 ????<100 ????<100
Table 25
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.2×10 6 ????2.9×10 6 ????7.8×10 6 ????5.5×10 6 ????7.2×10 5
0 hour ????7.9×10 5 ????5.0×10 4 ??????- ????2.7×10 5 ????9.0×10 4
48 hours ????<100 ????<100 ??????- ???????- ???????-
7 days ????<100 ????<100 ????<100 ????1.9×10 3 ????1.0×10 4
14 days ????<100 ????<100 ????<100 ????<100 ????3.2×10 4
21 days ????<100 ????<100 ????<100 ????<100 ????2.1×10 4
28 days ????<100 ????<100 ????<100 ????<100 ????4.4×10 4
Table 26
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.2×10 6 ????2.9×10 6 ????7.8×10 6 ????5.5×10 6 ????7.2×10 5
0 hour ????2.9×10 5 ????3.0×10 4 ????????- ????5.0×10 5 ????6.2×10 4
48 hours ????<100 ????<100 ????????- ???????- ???????-
7 days ????<100 ????<100 ????<100 ????<100 ????8.1×10 3
14 days ????<100 ????<100 ????<100 ????<100 ????5.4×10 3
21 days ????<100 ????<100 ????<100 ????<100 ????2.2×10 3
28 days ????<100 ????<100 ????<100 ????<100 ????5.0×10 2
Table 27
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.2×10 6 ????2.9×10 6 ????7.8×10 6 ????5.5×10 6 ????7.2×10 5
0 hour ????9.2×10 5 ????1.9×10 5 ???????- ????6.2×10 5 ????5.4×10 4
48 hours ????<100 ????<100 ???????- ???????- ???????-
7 days ????1.0×10 3 ????<100 ????3.5×10 3 ????2.1×10 5 ????3.1×10 4
14 days ????<100 ????<100 ????2.0×10 2 ????5.5×10 3 ????7.6×10 3
21 days ????<100 ????<100 ????<100 ????3.8×10 4 ????2.8×10 3
28 days ????<100 ????<100 ????<100 ????1.9×10 5 ????2.0×10 3
Table 28
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.2×10 6 ????2.9×10 6 ????7.8×10 6 ????5.5×10 6 ????7.2×10 5
0 hour ????7.0×10 4 ????8.0×10 3 ???????- ????6.2×10 5 ????5.8×10 4
48 hours ????<100 ????1.3×10 3 ???????- ???????- ???????-
7 days ????<100 ????<100 ????<100 ????<100 ????9.0×10 2
14 days ????<100 ????<100 ????<100 ????<100 ????<100
21 days ????<100 ????<100 ????<100 ????<100 ????<100
28 days ????<100 ????<100 ????<100 ????<100 ????<100
Table 29
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.2×10 6 ????2.9×10 6 ????7.8×10 6 ????5.5×10 6 ????7.2×10 5
0 hour ????5.7×10 5 ????1.1×10 5 ???????- ????2.2×10 5 ????7.0×10 4
48 hours ????<100 ????<100 ???????- ???????- ????????-
7 days ????<100 ????<100 ????<100 ????1.4×10 5 ????7.1×10 3
14 days ????<100 ????<100 ????<100 ????1.7×10 3 ????3.7×10 3
21 days ????<100 ????<100 ????<100 ????<100 ????<100
28 days ????<100 ????<100 ????<100 ????<100 ????<100
Table 30
Time point Staphylococcus aureus ATCC6538 Pseudomonas aeruginosa ATCC9027 Escherichia coli ATCC8739 Candida albicans ATCC10231 Black aspergillosis ATCC16404
Inoculum ????3.2×10 6 ????2.9×10 6 ???7.8×10 6 ????5.5×10 6 ????7.2×10 5
0 hour ????7.2×10 4 ????3.0×10 2 ??????- ????3.7×10 5 ????7.0×10 4
48 hours ????<100 ????<100 ??????- ??????- ??????-
7 days ????<100 ????<100 ????<100 ????<100 ????<100
14 days ????<100 ????<100 ????<100 ????<100 ????<100
21 days ????<100 ????<100 ????<100 ????<100 ????<100
28 days ????<100 ????<100 ????<100 ????<100 ????<100

Claims (28)

1, a kind of antiseptic composition, it comprises:
(i) tea tree oil of 0.10-2.0%;
The (ii) alcohol that replaces of the phenyl of 0.10-2.0%; With
(iii) one or more are used for the solvent of the alcohol of tea tree oil and phenyl replacement.
2,, further comprise a kind of solvent that is used for the alcohol of tea tree oil and phenyl replacement according to the antiseptic composition of claim 1.
3, according to the antiseptic composition of claim 2, wherein, solvent is a water.
4, according to the antiseptic composition of claim 2, wherein, solvent is at least a kind of polar organic solvent.
5, according to the antiseptic composition of claim 4, wherein, solvent is at least a kind of in ethanol, methanol, propylene glycol, butanediol, ethylene glycol or other polyhydroxyalkanes.
6, according to the antiseptic composition of claim 2, wherein, solvent is a natural oil.
7, according to the antiseptic composition of claim 6, wherein, natural oil is olive oil.
8, according to the antiseptic composition of claim 6, wherein, natural oil is simmondsia oil.
9, according to the antiseptic composition of claim 6, wherein, natural oil is Macadamia nut oil.
10, according to the antiseptic composition of aforementioned each claim, wherein, the alcohol that phenyl replaces is benzyl alcohol.
11, according to each antiseptic composition of claim 1-9, wherein, the alcohol that phenyl replaces is phenethanol.
12, according to each antiseptic composition of claim 1-9, wherein, the alcohol that phenyl replaces is phenyl phenol.
13, according to the antiseptic composition of aforementioned each claim, wherein, the alcohol that phenyl replaces is natural extract.
14, according to the antiseptic composition of aforementioned each claim, wherein, TTO equates with the concentration of the alcohol that phenyl replaces.
15, according to each antiseptic composition of claim 1-13, wherein, the merging concentration of TTO and phenyl alcohol is 1%w/v.
16, according to the antiseptic composition of claim 14, wherein, the concentration of TTO is 0.5%w/v, and the concentration of phenyl alcohol is 0.5%w/v.
17, according to the antiseptic composition of claim 17, wherein, the concentration of TTO is 0.5%w/v, and the concentration of phenyl alcohol is 0.5%w/v.
18, according to the antiseptic composition of aforementioned each claim, wherein, contain 10% water at least.
19, a kind of antiseptic concentrate, it comprises:
(i) tea tree oil of 20-80%;
The (ii) alcohol that replaces of the phenyl of 20-80%;
The (iii) surfactant of 0-80%; With
The (iv) dispersant of 0-80%.
20, according to the antiseptic concentrate of claim 19, it comprises the surfactant of 25-80% and the dispersant of 20-80%.
21, according to the antiseptic concentrate of claim 19, the alcohol that its phenyl that comprises the TTO of 30-50% and 30-50% replaces.
22, according to the antiseptic concentrate of claim 19, the alcohol that its phenyl that comprises 40% TTO and 40% replaces.
23, according to the antiseptic concentrate of claim 19, wherein, the alcohol that phenyl replaces is selected from benzyl alcohol, phenyl phenol and phenethanol.
24, according to the antiseptic concentrate of claim 23, wherein, the alcohol that phenyl replaces is benzyl alcohol.
25, according to the antiseptic concentrate of claim 19, wherein, surfactant is a non-ionic surface active agent.
26, according to the antiseptic concentrate of claim 25, wherein, non-ionic surface active agent is a polyoxyethylene surfactant.
27, according to the antiseptic concentrate of claim 19, wherein, dispersant is a polyhydroxy-alcohol.
28, according to the antiseptic concentrate of claim 19, wherein, dispersant is a propylene glycol.
CN98805398A 1997-03-24 1998-03-24 Preservation composition containing tea tree oil (TTO) Pending CN1257432A (en)

Applications Claiming Priority (2)

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AUPO5835A AUPO583597A0 (en) 1997-03-24 1997-03-24 Preservative composition containing tea tree oil
AUPO5835 1997-03-24

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JP (1) JP2001517236A (en)
CN (1) CN1257432A (en)
AU (1) AUPO583597A0 (en)
CA (1) CA2284711A1 (en)
WO (1) WO1998042386A1 (en)
ZA (1) ZA982456B (en)

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CN105358125A (en) * 2013-06-28 2016-02-24 隆萨有限公司 Synergistic preservative blends

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NZ332694A (en) 1998-11-06 2001-03-30 Coast Biolog Ltd Antimicrobial composition containing manuka oil (leptospermum scoparium) and Australian tea tree oil (melaleuca alternifolia)
WO2002015864A2 (en) * 2000-08-25 2002-02-28 Unilever Plc A vehicle and concentrates for customized personal care products
WO2003045340A1 (en) * 2001-11-27 2003-06-05 Unilever Plc Hair treatment compositions
JP2009161585A (en) * 2007-12-28 2009-07-23 Yushiro Chem Ind Co Ltd Water-soluble metal working fluid composition
EP2295114A1 (en) 2009-09-10 2011-03-16 Dalli-Werke GmbH & Co. KG Cosmetic compound with antimicrobial effect
BR112012028279A2 (en) * 2010-05-05 2017-05-23 Biomor Israel Ltd "combinations of antifungal compounds and tea tree oil"
GB2523340A (en) * 2014-02-20 2015-08-26 Sheikha Fatima Al Thani Composition

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US5009890A (en) * 1987-08-10 1991-04-23 Trilling Medical Technologies, Inc. Burn treatment product
US5096709A (en) * 1988-05-09 1992-03-17 Melaleuca, Inc. Muscle relaxant and analgesic containing oil of Melaleuca, spp.
US5215748A (en) * 1990-10-22 1993-06-01 Mankovitz Roy J Topical preparation and method for suppression of skin eruptions caused herpes simplex virus

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100459972C (en) * 2006-11-07 2009-02-11 华南农业大学 Anti-acne moisturizing cream and preparation process thereof
CN105358125A (en) * 2013-06-28 2016-02-24 隆萨有限公司 Synergistic preservative blends
CN105358125B (en) * 2013-06-28 2018-07-06 隆萨有限公司 Cooperate with preservative blends

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AUPO583597A0 (en) 1997-04-24
CA2284711A1 (en) 1998-10-01
ZA982456B (en) 1998-09-23
EP0983092A1 (en) 2000-03-08
JP2001517236A (en) 2001-10-02
WO1998042386A1 (en) 1998-10-01

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