TW201114450A - Preservative system for emulsion-based therapeutic topical formulations - Google Patents

Abstract

A topical formulation that inhibits the growth of microorganisms comprises an effective amount of an insecticide dissolved in an oil phase comprising a water-miscible or water-soluble surface active agent, a suspending agent, and a non-ionic surfactant, and an aqueous phase comprising one or more preservatives, where the aqueous phase is buffered to a specific pH. The overall antimicrobial efficacy in an emulsion formulation can be enhanced by buffering the aqueous phase of the emulsion to a pH at which the preservative system inhibits growth for a wider variety of microorganism types in the formulation relative to the equivalent formulation in which the aqueous phase is not buffered.

Description

201114450 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates generally to the field of formulation chemistry. Further, the accompanying invention of the 10n-based therapeutic topical preparation relates to an improved emulsion of bacteriocin=sex:==r, in the said: the production of the same emulsion of the production of m ^ no buffer . . The shelf life (shdflife), and the oxidative isomerization is also inhibited. , '',, ° [Prior Art] Milk Qi; use, local delivery of therapeutic active agents are extensive:). The emulsion is a combination of an oil phase and an aqueous phase (_〇_〇夕卜的单流, which has several water-based or oil-based groups = the advantage that the kg cannot provide. First, by the oil phase and water II :: It is possible to formulate hydrophilic and hydrophobic ingredients in a single "and", followed by an oil component, but the milk is from the consumer's = because it does not have a pure oil-based formulation - a greasy feel : ί 'And can' be the most important for topical therapy, the emulsion has a flow = sex (rh_gy) 'which is stable at rest, but exhibits a decreasing viscosity when applied with increasing shear stress. This will facilitate local Apply, but after application, the emulsion no longer flows or drip, and remains in the application area where the therapeutic treatment is required. This is particularly beneficial for topical compositions used in the treatment of heads. The time to effectively eradicate the head lice must be securely retained at the application site. Watery products will quickly flow down the forehead and crotch, making the application uncomfortable and ineffective. The emulsion should remain stable to retain its location. Need for rheological properties. Separation from the water component will reduce the viscosity and produce a product that has oil (iv) and will not be retained when applied, in a suitable location, easy to drip, easy-flowing products. The emulsion-based topical treatment product should be in its intended life (useful life) It remains stable. The active agent must also remain stable. It is known that avermectin undergoes catalytic isomerization to form 2-epimer impurities, which are substantially more comparable to the basic products. Low biological activity. Moreover, oils and other emulsion components suitable for topical application act as microbial feedstocks such as fungi and fine g. If left unchecked, the growth of microorganisms in the sword will be given to the head. The injected patient poses a risk of infection. Furthermore, the resulting microbial biomass has an unpleasant odour and appearance and can & otherwise render the product unsuitable for skin contact. There is a need for improved emulsion preservation systems. SUMMARY OF THE INVENTION A bribe service organism grows a resistant topical preparation, said microbacteria, yeast, fungi, mold, and the like. The i dose generally comprises an effective amount of insecticidal Solution to the oil phase and the aqueous phase, or the water-soluble surfactant, suspending agent and non-separating agent's description of the aqueous phase including - preservatives and buffered τ, (4) the aqueous phase is unbuffered υ π read Compared with the four-effect preparation, the resistance to microbial growth reaches 201114450 -/TV~TA ptx, or the other is microbicidal (micr〇bicidai). The insecticide preferably includes avermectin, such as Ivy. Ivermectin, doramectin, selamectin or abamectin' or a combination thereof. Preferably, ivermectin. Insecticides may include Spinosyn, such as Shibayouxin factors a, b, c, d, e, f, g, h, j, k, l, m, spinosad is a better Sbnosin . Ivermectin may be included at a concentration of from about 0.1% to about 1% by weight of the formulation. When ivermectin and spinosad are used, the combined concentration may range from about 0.1% to about 5% by weight of the formulation. The pH is preferably buffered in the range of from about 4.5 to about 6.2. Preferably, the buffering agent comprises or comprises citric acid and/or sodium citrate, which may range from about 0.01% to about 1% citric acid and from about 1% to about 125% sodium citrate by weight of the formulation. Farming is added. The oil phase may comprise from 20% to 35% of the suspending agent by weight of the formulation, and the suspending agent may comprise olive oil, shea butter or a combination thereof. The eucalyptus oil may comprise from 25% to 28% by weight of the formulation, and the shea oil may comprise from 1% to 5% by weight of the formulation. The oil phase may comprise from 15% to 45% of the nonionic surfactant by weight of the formulation and the nonionic surfactant may comprise oleyl alcohol, lanolin (lan〇lin alc〇h〇1) , sorbitan tristearate, or a combination thereof. The oil phase may comprise from 10% to 20% water-miscible or water-soluble surfactants by weight of the formulation' and the water-miscible or water-soluble surfactant may comprise 6 201114450 polysorbate 80, acetic acid Cetyl acetate, acetylated lanolin alcohol, inferior combination. The formulation preferably comprises a preservative such as methylparaben and propylparaben, which may be present in the formulation at a combined concentration of from 0.01% to 2% by weight of the formulation. . The formulation may include a conditioner such as cyclomethicone. The concentration of the conditioning agent may range from 1% to 5% by weight of the formulation. The present invention also provides a method of enhancing the resistance of a topical emulsion to the growth of microorganisms. The method of microbial growth comprises -, money, and/or yeast growth. The method generally comprises buffering an aqueous phase of the emulsion to a value, In pH i, the larger amount of microbial growth is repressed in the equivalent formulation of the unprepared or buffered, neutral or pH value of the aqueous phase. Preferably, the emulsions described herein are included. The pH field is flushed to an aqueous phase of m η ^ -! ^ k ^ in an amount of from about 4.5 to about 6.2, including an effective amount of a buffering agent for citric acid and/or sodium citrate. Preferably, in the method of a, ❹ includes the preparation of imipenem, the isomerization of oxytocin. Alternatively or as an alternative - inhibition of base catalysis, the invention also provides a method of susceptibility or resistance to infection. In general, the treatment of an individual (such as a human) caused by a head strain that is susceptible to infection is characterized by a method of locally administering an effective amount to the individual. If: more = /: each use is shorter or better than 5 to 9 days.乐贝j母: The time between people giving music [Embodiment] (4) In the scope of application for patents, various terms related to the invention and its aspects are used. Unless the term is used in its ordinary meaning in the art. The singular forms "-" and "said" are used in the singular and "s" As used herein, the term "about" is intended to encompass a change from a specified value or ± 10%, more preferably ± 5%, even more preferably ± 1% and even more preferably ± 〇 1%. In accordance with the present invention, it has been observed that by buffering the aqueous phase to between about 4.5 and about pH 6.2, the antimicrobial properties of the emulsion will be enhanced. Accordingly, the present invention provides a topical emulsion comprising a preservative, wherein the resistance of the formulation to microbial growth is unbuffered or buffered to a more acidic, neutral relative to the aqueous phase when the aqueous phase of the emulsion is correspondingly applied. A similar formulation having an alkaline pH is enhanced. The invention also provides a method of enhancing the microbial resistance and/or antimicrobial properties of a topical emulsion. The topical preparation of the present invention may be an aqueous dispersion containing an oil phase of a therapeutically active ingredient. The aqueous dispersion can be prepared as a water-in-oil emulsion or an oil-in-water emulsion depending on the rheological properties desired by the product formulator. Formulation technicians familiar with personal care products such as Wash 8 201114450 JHVJHlpll shampoo and hair conditioner will understand how to formulate the ingredients disclosed herein into a water-in-oil or oil-in-water emulsion. The formulations of the invention are particularly suitable for topical application of therapeutically active ingredients which are hydrophobic and poorly water soluble. Accordingly, the therapeutically active ingredient is preferably dissolved in a suitable reagent to improve the stability of the active ingredient in water. These agents are preferably readily soluble in water or water miscible and comprise, for example, a surfactant comprising a water a or water miscible surfactant. Water-soluble and water-miscible The surface active age contains a compound which can dissolve the active ingredient in the active ingredient domain and is stable in water. A particularly preferred topical emulsion comprises an oil phase and an aqueous phase, wherein the active ingredient is dissolved in the oil phase. The oil phase preferably comprises three components: a solubilizer, a nonionic surfactant, and a suspending agent. The active agent r · U ^ car is also known as a pesticide or insecticide (msectief), and more preferably can kill good insecticides.

This "four" is about Avi Time #A which is suitable for use as an infection agent. It is easy to be infected or resistant to treatment U. The infection (4) can be prescribed for treatment or main 22, insecticide, In particular, the usual "Ai" contains Yi-resistant people. Suitable for shame, avermectin, ^=素^: serramycin, eprinomectin and aba _. Epinocin It is preferred that the preparation be in the form of a vitamin 8. One or more of the various concentrations of the A. vivax 201114450, for example, by weight of the preparation, about 0 005% to about 5% β, for example, containing 1% avidin The formulation will contain 1 gram (gram, g) of avermectin per ml, ml). In some aspects, the concentration of avermectin is from about 0.1% to about 2% by weight of the formulation. In the present invention, it has been observed that the concentration of ivermectin in 〇25%, 〇5%, and 1% promotes the effective killing of the permethrin-resistant cockroach cultivar. It can be utilized in more than 8〇% of 22,23_ Dihydroavermectin

a mixture of Bla and 22,23-dihydroavermectin Bib of less than 20 〇/〇, preferably up to 90% of 22,23-dihydroavermectin, and less than 1% by weight of 22,23 - Iphone in the form of a mixture of hydrogen and abbinib. For example, the preparation may be dissolved in about 5% to 5% by weight, about 〇1: 里:重重量%, or about 2525.5% to 1% by weight of avermectin, such as Ivermite Prime. ^ 4 Preparations may include at least one species of avermectin, lighter and less sympathetic, 1 benoxin, 0.00 0.005% to about 5% (heavy weight of the ^^, for example, the ratio of 100% in the preparation) Different concentrations exist. Take 0.1% to 5 Yuandan. / Solution has about 0. 05% by weight to 5% by weight, and about: 2: 2. Weight% to 2% by weight or about. _25 C, D history 3 Xin but not limited to) Individual Spanosin * A, Β, T'U'V> W^>J'K'L'M'N'〇'P>Q^Rs^ Xin factor (four) section, killing technology Shibino history #辛Α accounted for about 85% and Shibinoxin (four) about ^ ice 201714450 ipu combination of Sibenoxin and avermectin can account for the weight of the preparation to,,, The scoop is 2% by weight, and preferably 〇.5% to 3〇/〇 of the weight of the formulation. It is especially preferred that the insecticide or insecticide combination has been dissolved and maintained in the oil phase. Preferably, the active agent does not precipitate out of solution. The oil phase of the solubilized emulsion d may comprise one or more solubilizers. The solubilizing agent may comprise a synthetic or water miscible surfactant, or a combination thereof. The water-soluble or water-soluble granules may comprise at least about (7)% by weight of the formulation. In one such sample, the reagent comprises from about 1% to about 5% by weight of the formulation, and in some cancers, the agent comprises from about 2% to about 5% by weight of the formulation. In the preferred state & this reagent comprises from about 10% to about 20% by weight of the formulation. Any suitable water-soluble or water-miscible surfactant can be used. , non-limiting '! The raw examples include polysorbate 〇 8 〇, acetic acid vinegar and ethylene lanolin alcohol, or a combination thereof. Crodalan AWS is available from Cr〇da Chemicals and is a suitable reagent including polysorbate 8 oxime, cetyl acetate and acetylated lanolin alcohol. The polysorbate 8 oxime may be present in the formulation from about 5% by weight to about 25% by weight, from about 10% by weight to about 15% by weight, and preferably from about 11.25% by weight to 13.5% by weight, based on the weight of the formulation. From about G. 5 wt% to 1 wt%, from about 1 wt% to 4 wt%, and preferably from about 1.50 wt% to 375% wt% of cetyl acetate may be present in the formulation, based on the weight of the formulation. It may be present in the formulation in an amount of from about 1% by weight to about 3% by weight, based on the weight of the formulation, from about 0.5% by weight to about! % by weight and preferably 〇 15% by weight to 〇 % by weight 11 201114450 % of acetaminophen. In some of these, there is a water-soluble or water-miscible surfactant that can ensure that the active ingredient is stable at the aqueous level of the emulsion. In this aspect, fine shots may be present in an amount less than 30% by weight 'such as less than 25%, or below 鸠, or below 15%', or below 1G%' or below 5 % of the pharmaceutically acceptable diol to make the treatment live (iv) read any diol, especially propylene glycol or polyethylene glycol. The oil phase of the 匕3 suspending agent can include one or more suspending agents. In some aspects, a combination of j fatty oil and/or fat can be used as a suspending agent. Examples of suspending agents include, but are not limited to, eucalyptus oil, shea butter, cocoa butter, vegetable oils, and their analogs. The two fatty acids are linked to the glycerol backbone, and the tallow is added to the glycerol backbone. Tree oil is mainly made of palmitic acid, stearic acid, oleic acid, linoleic acid and floral acid fatty acid. Although these fatty acids have been used as "homeremedy" to remove head lice from the scalp, they do not kill head lice. Olive 'sole' is a viscous material that slows the movement of adult lice to remove it better. The combination of olive oil and shea oil is the preferred suspending agent. The content of the olive oil present in the preparation is set to be about 20% to 30%, and preferably about 25% to 28% by weight (j female, '27.5% by weight) based on the weight of the preparation. The amount of shea butter present in the formulation may range from about 1% to about 5%, and preferably about 2% by weight. Other known suspending agents useful in the formulations and related methods include ( But not 12 201114450

Limited to) coconut oil, palm oil, cottonseed oil, vegetable oil, soybean oil, eucalyptus oil, peanut oil, corn oil, sunflower oil, safflower oil, jojoba oil (j〇j〇ba oil), canola oil ( Canola oil), shea butter, cocoa butter, milk fat, amaranth oil, apricot 〇il, argan oil, avocado oil (avocad π), Babassu 〇il, ben oil, carob oil (aiga_r〇ba 〇ii), coriander seed oil, linseed oil (faise f|ax), grape seed oil , hemp oil, kap〇k seed oil, meadowfoam seed oil, okra seed oil (〇kra seed 〇u ), perilla seed oil ), poppy seed oil (p〇ppy _ 〇n ), prune kernel oil, pumpkin seed oil, quinoa oil ramtil oil, rice bran oil (such as _ (8))' camellia Camellia oil, thistle 〇il, wheat germ oil (heart coffee plus oil): and combinations thereof. Fatty acid glycerin vinegar can be used and is known to be used as a skin moisturizer. Nonionic surfactant The oil phase of the emulsion may include one or more nonionic surfactants. The non-3 surfactants are contained in the water Hx and the water-oil interface by the combination of the wettability, emulsion stability, foaming ability, rheology, lubricity and surface conditioning properties of the two. · Alcohol or fat _ mixing = agent. In addition to the active ingredient, the active ingredient conditioner (shamp〇0-conditi〇ner) / / : road 5, hair essence _, non-μ work ^ 之 called the final product used in the preparation of the W Non-ionic interface activity _ plays a variety of 13 201114450 role in the surface chemistry of the formulation. In addition to its surface-active properties, fatty alcohols are emollients that make the skin smoother, and they act at the water-air and water-oil interfaces, thereby enhancing the wetting ability, emulsion stability, and foaming ability of the formulation. , rheology, antistatic, lubricity and surface conditioning properties. Emollients contain compounds that soften and smooth the skin by preventing the skin from losing moisture. Examples of suitable nonionic surfactants include, without limitation, oleyl alcohol, lanolin alcohol, sorbitan tristearate, erucyl alcohol, ricinolyl alcohol, arachidyl alcohol (arachidyl alcohol), capryl alcohol, capric alcohol, behenyl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, Stearyl alcohol, isostearyl alcohol, oleyl alcohol, paimit〇ieyi alcohol, linoleyl alcohol, 9E-octadecene-1·ol (eiaidyl) Alcohol), 9E, 12E-elaidolinoleyl alcohol, linolenyl alcohol, 9E, 12E, 15E-elaidolinolenyl alcohol, and combinations thereof. In some preferred aspects, the formulation comprises a combined concentration of from about 10% to about 35%, or preferably from about 15% to about 24%, and more preferably from about 18% to about 24% by weight of the formulation. % of nonionic surfactant. Nonionic surfactants preferably include oleyl alcohol, lanolin alcohol, and sorbitan tristearate. In some aspects, from about 5% to 15% by weight, and preferably from about 1% by weight, of oleyl alcohol may be present in the formulation, based on the weight of the formulation. From about 3% by weight to about 15% by weight, more preferably about 5, by weight, from 201114450% to 10% by weight, and more preferably about 8% by weight, of lanolin alcohol may be present in the formulation. Dehydrated sorbitan distearate is commercially available as Glycomul® TS (Lonza) or as SPAN 65 sold by Merck Schuchardt OHG. Dehydrated Sorbitol tristearate is a low hydrophilic-lipophilic balance (HLB) ester-based surfactant and has many uses in the food and cosmetic industries. The chemical structure of sorbitan tristearate is defined by a five-membered cyclic ether having a hydroxyl group and three fatty acid side chains. About 0.1% by weight to 3% by weight, preferably about 0.5% by weight, of sorbitan tristearate may be present in the formulation based on the weight of the formulation. Conditioning Agents Polyoxyxides can be added to the formulation, and in some aspects, preferably added to the oil phase of the emulsion for use as a skin or hair conditioning agent. Conditioning agents can alter the texture, feel, and appearance of a person's hair. Other conditioning agents other than polyoxyxides can also be used. In some aspects, the polyoxyxene compound can be selected from the group consisting of volatile polyoxyxides, one of which is cyclomethicone. The cyclic polyoxyalkylene can act as a conditioning agent in a formulation intended for application to hair, such as shampoo-conditioner. It leaves the hair silky smooth and evaporates quickly, leaving very little residue. The formulation may comprise from about 1% to about 5% by weight, and preferably about 3 parts by weight, based on the weight of the formulation, of a cyclopentanol. Examples of useful conditioning agents include, but are not limited to, guanidine I, oxysulfonation, dimethicone, hexamethyldisil0Xane, octamethyltrisiloxane (octamethyltrisiloxane). ), decamethyltetrasiloxane, dodecamethylpentasiloxane, polydimethylsiloxanes, and combinations thereof. The preservative formulation preferably includes a preservative to inhibit the growth of the microorganism and/or to prevent chemical breakdown of the formulation. In one such hybrid, the preservative may be selected from the group of compounds in the paraben family. The ^hydroxybenzoate preferably comprises decyl p-hydroxybenzoate, propyl p-hydroxybenzoate or a combination thereof. The preservative is preferably water soluble and is preferably included in the aqueous phase of the emulsion. In some aspects, the concentration of the preservative in the formulation is from about 0.05% to about 2% by weight of the formulation. The formulation may contain from about 0.01% to about 2% by weight, preferably from about 3% by weight to about 3% by weight, and more preferably about 0.2% by weight, based on the weight of the formulation. The agent may be present in an amount of from about 0.01% by weight to about 9% by weight, and more preferably from about 〇 〇 to about 〇5 by weight. More preferably, from about 5% by weight to about 5% by weight, and more preferably about 0.1% by weight. The pair of benzoic acid (four). Other suitable preservatives include, but are not limited to, for the purpose of the benzoic acid, for the benzoic acid, for the phenyl hydrazine, for the butyl phthalate, for the butyl vinegar, for the benzene. The pH of the isopropyl formate, the benzoic acid benzoate and the salt iso pH adjusting agent and the buffer preparation are preferably from about 1 Torr to about 65. Preferably, the positive value is between about 4.0 and about 6.5, the pH is preferably between about 4 and about 5, the pH is preferably between about 4.5 and about 6 Torr, and the pH is preferably between about 5 Torr. Between about 6.0 and pH is even better between about 5 3 and about $8. 201114450 Especially good for the pH value of human skin. Buffers capable of buffering the aqueous phase to a pH between about 4 5 and about 6.2 are very common and readily identifiable to those skilled in the art. Such buffers include, for example, citrate buffers, acetate buffers, dishate buffers, tartrate buffers, fumarate buffers, dimercaptoglutarate buffers. , succinate buffer, phthalate buffer, maleate buffer, and mixtures thereof. Preferably, the agent comprises a biologically acceptable carboxylate capable of buffering the aqueous phase of the emulsion, non-limiting examples of which are described in the foregoing list. The combination of citric acid and sodium citrate, preferably the beta pH adjuster, may be incorporated directly into the formulation in its solid form or may be added as part of a liquid or solid buffer comprising a plurality of reagents. In some aspects, the formulation comprises from about 0.01% to about 0.1% by weight, and preferably from about 55% by weight, of citric acid, based on the weight of the formulation. In some aspects, the concentration of the citric acid is from about 1% by weight to about 1.25 % by weight based on the weight of the formulation, preferably about 1 〇 99% by weight of citric acid. The amount of citric acid and/or sodium citrate may vary depending on the desired pH to be achieved by the formulation. In a particularly preferred aspect, about 55% by weight of citric acid is used in combination with about 1.099% by weight or about 1.1% by weight sodium citrate. These agents can provide antimicrobial activity by themselves independent of the preservative and, in some aspects, can be used in place of a separate preservative. Sodium phosphate and/or sodium monohydrogen phosphate and sodium dihydrogen can also be used in combination with citric acid and/or sodium citrate. Other suitable buffers include those comprising acetic acid and/or acetic acid. In some aspects, when avermectin is used as a therapeutically active ingredient, a buffer can also be used to prevent isomerization of avermectin to the 2-epimer. Other suitable preservatives include sodium benzoate, imidazolidinyl urea (such as the GERMALL preservative family, including GERMALLPLUS), sequestering agents (such as ethylenediamine tetraacetic), either alone or in combination with the free acid. Acid, EDTA)) and related compounds at various stages of protonation, as well as citric acid and its sodium salt. Other suitable preservatives present in the formulation may be present in the same concentration range as the parahydroxybenzoate, for example, in an amount of from about 0.01% to 2% 'or from about 0.1% by weight to about 5% by weight (e.g., 0.05% by weight) ◦/〇). Humectant In some aspects, the formulation may further comprise a humectant. Humectants are hygroscopic materials intended to prevent the formulation from drying out during use and before being washed away from the skin, hair or scalp. Humectants can also act as moisturizers in shampoo and conditioner formulations. The humectant is generally a molecule having a number of hydrophilic groups such as a hydroxyl group, an amine, a carboxylic acid group and an ester thereof which enables the molecule to form a hydrogen bond with water molecules. In some aspects, other components of the formulation have the dual function of acting as a humectant, such as many nonionic surfactants including, but not limited to, oleyl alcohol, lanolin alcohol, acetylated lanolin alcohol, and the like. . In another embodiment, the humectant is selected from the group consisting of glycerin, triacetin, sorbitol, xylitol 'maltitol, polydextrose, quillaia, lactic acid, urea, and the like, and mixture. Water dissolved with therapeutically active ingredients, suspending agents, solubilizing agents and non-ionic interfaces 201114450 jw^fipir The active oil-based compound can be separated from the water t, or dispersed in the oil phase. In some aspects, the water is deionized. Water acts as a carrier and is approved for use in any individual gamma. Illustrated as a towel, the formulation may be present in an amount of from about 30% to about 4% by weight, preferably from about 3% by weight to about 33% by weight, based on the weight of (iv). And preferably about 32% by weight water. Adding an oil phase comprising a therapeutically active ingredient to deionized water produces a live, component-like suspension 'where the micelles form mice mie e) and which are made to make the boundary (tetra) agent hydrophilic, _ with solvent water ^' Contact the hydrophobic tail of the surfactant with the active ingredient. This, 1 Temple is suitable for the therapeutic activity of shower gel and shampoo hair conditioner. Hair conditioner - conditioner, which makes the product easy to wash off and flow, so that the hair is in good condition. / The formulation of the present invention will utilize, but is not limited to, the one disclosed in the table: agent::: Ming. The consistency of this formulation is in combination with shampoo-conditioner or ointment in this formulation, water, suspending agent, interfacial activity (W/V). The concentration of the pulse-correcting line 11 is 0.50%. This skill is a standard money 3, and it does not limit the scope of the invention used by the invention. 19 201114450 Table % (by weight) 0.50 31.75 27.75 15 0.055 1.099 10 8 3 2 0.50 0.25 0.10 Ingredients therapeutic active USP grade deionized water NF grade olive oil AWS grade Crodalan USP grade citric acid USP grade sodium citrate NF grade oil Alcohol NF-grade lanolin alcohol NF-grade cyclic oxime polyoxane avocado oil sorbitan tristearate NF-grade hydroxybenzoic acid oxime ester NF-grade hydroxybenzoic acid propyl ester content component, known Equivalent components, combinations of components, and individual concentrations can be readily adjusted to provide alternative formulations for the purposes disclosed herein. Therefore, those skilled in the art will appreciate that the weight of any component can be adjusted to compensate for the concentration, texture or rheology of the active ingredient of the topical formulation and to represent it as a water-in-oil emulsion. (d) (e.g., wash = revolution), and the components may be added at different concentrations, or may be substituted with or with equivalent components, thereby providing an exemplary embodiment as described herein. A topical preparation similar to the sputum preparation. Invention = Skills; = Understanding 'Additional useful agents can be added to the present hair, which include, without limitation, vitamins, vitamins, and . A formulation or a combination thereof such that at least one useful agent does not eliminate the useful aspects of the formulation by 201114450 J4U41pir. The present invention also provides a formulation for enhancing the growth of microorganisms. The resistance to microbial growth is described herein and/or exemplified. η The method is large #2, and the anti-microbial value of the formulation is additionally enhanced, at the pH. The value of the anti-mite includes buffering the amount of the emulsion to a certain amount of yang than the pH value of the unbuffered or slow-reducing agent in the microorganism growth system _ comparison _:;: true etc. sex, agent, can be Qiu The value is adjusted to the assay and the aqueous phase is buffered to buffer to an acidic pH. Using a higher or lower pH ^ ΐ P . 5 to about pH 6.2, but also 6, or any other p; phase described herein buffered to about pH 5 to about yang plus (d) an effective amount of citric acid and / or the sodium sulphate additive === the amount of effect can vary, and is preferably sufficient to make the 'aqueous phase can include, by weight of the formulation, about H and about 1% to about L25, lemon Sodium. These agents provide antimicrobial activity by themselves and, in some aspects, are used in place of preservatives. In the case of the above-mentioned methods, the method is applied to inhibit the activity of the catalytic activity such that the preparation is buffered to inhibit the isomerization of the active ingredient (in time, square, and element). For example, when the formulation comprises ivermectin can include buffering the formulation to a pH sufficient to inhibit base-catalyzed isomerization of ivermectin 21 201114450. For composite liquids, such as the formulations described and exemplified herein, it is not previously known whether the pH of the buffered aqueous phase will affect the stability of the components of the oil phase, given that the oil phase component is transiently exposed to the aqueous phase. Since the pH value induces avermectin isomerization (pivnidmy, JV et al. (1988): Γ· Agric·Food Chem 36: 826-8), it is now known to dissolve avermectin. Acidification of the pH of the aqueous phase of the emulsion in the oil phase will prevent or reduce the isomerization of the avidin. Therefore, the aqueous phase is preferably buffered. The pH sufficient to inhibit the isomerization of the base catalyzed active agent may vary depending on the particular active agent employed. For example, in the case of ivermectin, the aqueous phase is preferably buffered to a pH of from about pH 4.0 to about pH 6.5, including the ipH values described and illustrated herein, and more preferably buffered to the pH of human skin. For example, the oil phase and the water phase can be separately prepared by separately preparing the oil phase and the water phase (for example, by mixing the components of the phases together) according to any suitable means in the art. To prepare a topical preparation. It can be used to mix the oil phase with the water phase under various conditions (e.g., temperature X, heating and cooling rates, and the like) to ensure proper dispersion and stability of the resulting emulsion. & The init step of the present invention comprises the prevention or elimination of the head which is susceptible to infection or anti-treatment = the resistance of the formula can be riding on the current market, or in other aspects", any of the cephalosporin treatments known in the 'Technology' Health, such as marathon resistance or baijisheng (Μ-) resistance, pyrethrum (pyrethrum) resistance. The method utilizes the preparation of avidin and sinuoxin in a topical preparation. Included in the description or exemplification 22 201114450 A, the effective amount of the local package (4) requires (4) the treatment of the topical topical enhancement preparation or preparation; the topical emulsion includes aqueous phase buffer to be able to treat and better, 'Xiao (4) The anti-microbial properties continue to be sufficient for the treatment of a single dose of the coffee. The PH H is suitable for the individual to use multiple doses of Ϊ; =, according to the individual or the physician's decision, the preparation of the South contains 2 doses, 3 doses, 4 or more doses. 1 can be shampoo and conditioner) for 1 / person in about 7 days (for example, between day 1 and about day 5 and day 9), 9 Second day of the day (application started on the first day, followed by the second and third times in about 5 days to about + main interval) Or the 4th time. Each time the preparation is given and the infection site (such as the scalp) is kept for about 1 minute ^ ί f ' or about 3 minutes to about 3 minutes, then washed with warm water, can be used; Parts (such as the scalp) are guaranteed for $minutes to minutes' and (four) minutes for 15 minutes. Especially for about ι〇 minutes. Make the hair to keep the hair in good condition, and secret the secrets of the goods, turn the cranes and the farm Alternatively, it may be changed by changing the concentration of avermectin or sibinoxin as described above, or by increasing the amount of the topical preparation of the scalp of the individual, although Iveg and Schnauzer (d) with =, but also covers other known A-sin, other than I-su, and other known Sloan, except for killing, and can be used as a live-off of the present invention. 23 201114450 Despite the dose range Varying, but administration "single: a single application amount (dosage) === =) to juice to about 75 liters, more preferably about 50 liters to about 19n, and more preferably about 100 From milliliters to about 丨, depending on the amount and/or length of the hair. Therefore::, root can require a larger dose. Longer hair may, in some aspects, apply at least about 6 body saturation and effectively cover the entire scalp area. Practitioners 匕:: The concentration of i and smuggling, and / or bureau (four) _ the effective amount of ivermectin and spinosad administered by the individual. Inventive Nursing The additional cancerous form of the invention is a plurality of administrations of the avermectin (presence or absence of a sinnoxin) or ivermectin (presence or absence of a spinosad) base preparation of the present invention. The multiple doses may include at least one '2, 3 or 4 additional doses other than the initial dose, with one or possibly two external doses being preferred. It is known in the art that a similar treatment regimen can currently be used to treat not only the first infection, but also the infection of the wind (pUbiCHCe) or body wind (by (Jy lice) infection. Therefore, it is obvious that the present invention contains The preparation of avermectin can not only effectively treat head lice, but also treat sputum and body sputum infections of the human body. The preparation of the invention can be used for treating vaginal and/or body lice infections, and can change the core components in the preparation, To provide a formulation having the consistency of a cream rinse or lotion, which can be applied to the affected area, retaining a period of time expected for the treatment of the head, and then washed away. As described herein in relation to 24 201114450 Multiple administrations are also contemplated as contemplated by the formulations disclosed herein. The following examples are provided to describe the exemplary aspects of the invention in more detail. It is intended to illustrate and not to limit the invention. Formulation of shampoo conditioner can be prepared as a topical shampoo-conditioner as a topical shampoo-conditioner as follows: ivermectin is weighed and weighed to Pre-dissolved in a container containing a water-miscible surfactant (hereinafter referred to as phase A), that is, 15.00% w/v polysorbate S 80. While mixing, 'heating the phase at a constant temperature of 65 ° C Until ivermectin is completely dissolved in the surfactant. Subsequently, phase A is poured into a container containing phase B from the suspending agent 'preservatives, nonionic surfactants, humectants and conditioning agents Composition. Phase B consists of 27.25% w/v olive oil, 2.00% w/v shea butter, 8.00% w/v lanolin alcohol, 3.00% w/v cyclophosphazene, 〇5〇% w/ v sorbitan distearate, 0.20% w/v for hydrazinyl hydrazide and 0.05% w/v for propyl benzoate, while mixing, at a constant temperature of π Lower phase A and phase B until all components are dissolved and/or melted. At the same time, at a constant temperature of 85 °c, phase c is heated from 0.055% w/v citric acid and 丨〇99 w/v Sodium citrate buffered water = s. While vigorously mixing, phase A and phase B are slowly added to phase c. At room temperature or near room temperature, mixing is continued until a uniform and homogeneous formation is formed, followed by Line packaging # 25 201114450 Example 2 Preparation of ivermectin emulsion Weigh ivermectin and dissolve it in water miscible surfactant Aws grade Crodalan and oleyl alcohol, and heat the resulting solution (phase A) to 60 to 65 °C. Combine suspending agent, nonionic surfactant and conditioning agent (Phase B) and while mixing, 'heat it to 75 to 80 ° C, and make sure all ingredients are dissolved, the suspending agent, nonionic interface activity The agents and conditioners are respectively composed of: 27.25% w/v eucalyptus oil and 2.00% w/v shea butter, 8.00% w/v lanolin alcohol and 0.50% w/v sorbitan tristearate And 3.00% w/v cyclophosphazene. At the same time, thoroughly mix phase c and heat to 75 to 80 ° C, the phase C consists of water buffered with 0.055% w/v citric acid and 1.099% w/v sodium citrate, and methyl and hydroxybenzoate. It consists of propyl acetonate. Phase A is premixed with phase b, followed by vigorous addition of phase C. Mixing is continued until a homogeneous and homogeneous blend is formed. The mixture was allowed to cool to room temperature with continued mixing, after which the compounded formulation was packaged. Example 3 USP Antimicrobial Utility Test A topical ivermectin emulsion comprising an augmenting agent, a nonionic surfactant, and a suspending agent was prepared and according to the United States Pharmacopoeia (us pharmac〇p〇da, USP) Chapter 31, Section 51 (2008) (incorporated herein by reference), screening for antimicrobial efficacy. As shown in Table 2 below, one part of a preservative containing a benzoic acid-based preservative or a detoxified formic acid preservative with citric acid and a lemon-like emulsion was formulated. For "containing citric acid or rubbing sample 26 201114450 jw^ipir acid sodium. Table 2: ivermectin preparation control group 1 6 8 9 component% w/w % w/w % w/w % w/w % w /w USP grade pure water 33.00 31.85 26.85 31.75 32.85 Ivermectin 0.50 0.50 0.50 0.50 0.50 AWS grade Crodalan 15.00 15.00 15.00 15.00 15.00 NF grade oleyl alcohol 10.00 10.00 10.00 10.00 10.00 NF grade lanolin alcohol 8.00 8.00 8.00 8.00 8.00 8.00 grade EF olive Oil 27.75 27.75 27.75 27.75 27.75 Shea butter 2.00 2.00 2.00 2.00 2.00 sorbitan tristearate 0.50 0.50 0.50 0.50 0.50 NF grade cyclic oxime polyoxane 3.00 3.00 3.00 3.00 3.00 NF grade hydroxybenzoate 0.20 0.20 0.20 0.25 0.25 NF-grade propyl paraben 0.05 0.05 0.05 0.10 0.10 USP grade propylene glycol X NF grade butyl paraben X 0.05 USP grade citric acid USP grade sodium citrate X 0.055 0.055 0.055 X 1.099 1.099 1.099 Disodium Aminotetraacetate X Sodium Benzoate X Germall Plus Powder X USP Grade Glycerin X 5.00 Total 100.00 100.00 100.00 100.00 100.00 Table 2 (Continued) 12 14 17 20 25 26 Composition % w/w % w/w % w/w % w/w % w/w % w/w USP grade pure water 31.75 31.65 31.70 32.90 30.85 30.85 Ivermectin 0.50 0.50 0.50 0.50 0.50 0.50 27

201114450 1 piA AWS Grade Crodalan 15.00 15.00 15.00 15.00 15.00 15.00 NF grade oleyl alcohol 10.00 10.00 10.00 10.00 10.00 10.00 NF grade lanolin alcohol 8.00 8.00 8.00 8.00 8.00 8.00 8.00 NF grade eucalyptus oil 27.75 27.75 27.75 27.75 27.75 27.75 Shea oil 2.00 2.00 2.00 2.00 2.00 2.00 sorbitan tristearate 0.50 0.50 0.50 0.50 0.50 0.50 NF grade cyclomethicone 3.00 3.00 3.00 3.00 3.00 3.00 NF grade p-hydroxybenzoic acid methyl ester 0.20 0.25 0.20 0.20 0.20 0.20 NF grade经 曱 0.05 0.05 0.05 0.1 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Disodium acetate 0.10 0.10 Sodium benzoate 0.15 Germall Plus powder 0.10 USP grade glycerol 1.00 Total 100.00 100.00 100.00 100.00 100.00 100.00 According to USP, the compendial articles are divided into 4 categories, see Table 3. The standards for antimicrobial efficacy of these products vary with the route of administration. Table 3. Formulation Drug Categories Category Product Description 1 Injectables, other non-enteral preparations, otic products, sterile nasal products and ophthalmic products made from aqueous bases or vehicles. 2 A topical product made of an aqueous base or vehicle, a sterile nasal preparation, including those applied to the mucosa. Hole 3 An antacid made of an aqueous base, made of an aqueous base or vehicle. —— 28 201114450 USP test requires the cultivation of the following microorganisms: Candida albicans (a/Mca-like) (ATCC No. 10231), Black bacillus (J(10) mger) (ATCC No. 16404), Escherichia coli (along along c/^n'c) Coz_〇 (ATCC No. 8739), P. aeruginosa (Zero (9) also (10) like (10) such as) (atCC No. 9027) and Staphylococcus aureus (Aureus) (ATCC No. 6538) 'and the microorganisms used in this test are not available Different from the original ATCC culture for more than 5 generations. Inoculate each container with a prepared and standardized organism and mix. The volume of the inoculum suspension (suspensi〇n inoculum) used in the volume of the preparation is between 〇.5 Between % and 1%. After inoculation, the concentration of the test microorganism added to the preparation is between 1 〇 1〇5 per 1 ml of product and 10 菌 10 colony forming units (c〇lony_f〇rmingun worry, cfu) The inoculated containers were incubated according to the conditions described in Table 4. Each container was sampled at appropriate intervals as described in Table 5. The plate count procedure was used to determine the efu present in each test formulation at each applicable time interval. The number of uses At the beginning of the test, the concentration of cfu per ml was calculated, and the change of the 〇 〇 value per ml of cfu concentration at the applicable test interval was calculated, and the change was expressed according to the log reduction. Table 4. Culture conditions of the inoculum preparation Biological appropriate medium incubation temperature inoculum incubation time microbial recovery incubation time E. coli (ATCC No. 8739) Soybean Casein Digest Broth; soy casein digest agar 32.5 soil 2.5° 18 to 24 hours 3 To 5 days 29 201114450

3 to 5 days of Staphylococcus aureus (ATCC No. 6538) Candida albicans (ATCC No. 10231) Soybean casein digestion medium; Soybean cool protein digest agar 33⁄43⁄4 sugar agar (Sabouraud Dextrose Agar); Sabouraud glucose culture solution (Sabouraud Dextrose Broth) 32.5 ± 2.5. 22.5 ± 2.5° black bacillus (ATCC No. 16404) Sabouraud dextrose agar; Sabouraud dextrose broth 22.5 2.5° ± 18 to 24 hours 44 to 52 hours 6 to 10 days 3 to 5 days 3 to 5 days 3 to 7 days J table:! If the stated criteria are met, then the increase in resistance to micro-generation is defined as being no more than 0.5 loglO early than the previously measured value. Table 5. Standards for tested microorganisms

Yeast and mold 3 ΐ 1 gas reduction is not less than 2.q (four), and on the 28th day and 苐 28 days, compared to the initial count of the count did not increase, the following Table 6 provides the preparation selected from Table 2 Results of the USP antimicrobial efficacy test. Since the "control" preparation (see Table 2) was stored for several months under controlled 30 201114450 ipil laboratory conditions, mold growth was observed, even in the absence of specific inoculum, so it was determined that the preparation was unsuitable. Vaccination (data not shown). For Candida albicans, it was subsequently found that a small number of variants of the control formulation failed conventionally to pass the USP antimicrobial efficacy test. (Table 6: Ec = E. coli; Pa = Pseudomonas aeruginosa; Sa = Staphylococcus aureus; Ca = Candida albicans; An = Melanium). Table 6. Antimicrobial efficacy 7 days 14 days 28 days Formulation number organism / Dil CFU / g CFU / g CFU / g 8 Ec / 1 < 10 < 10 Pa / -1 < 10 < 10 Sa / -1 <10 <10 Ca/-1 235 <10 An/-4 6.5 x 105 3.0 x 103 17 Ec/-1 <10 <10 <10 Pa/-1 <10 <10 <10 Sa/-1 <10 <10 <10 Ca/-1 <10 <10 <10 <10 An/-4 1.6 x 105 1.2 x 103 30 9 Ec/-4 2.6 x 105 4.5 x 103 TNTC, TNTC Pa/-1 475 3.9 x 103 TNTC, TNTC Sa/-4 1.2 x 106 3.5 x 104 2.6 x 104 Ca/-4 8.4 x 105 45 TNTC, TNTC An/-4 4.4 x 105 2.3 x 105 9.5 x 104 20 Ec/-1 <10 <10 <10 Pa/-1 <10 <10 <10 Sa/-1 <10 <10 <10 <10 Ca/-1 80 <10 150 An/-1 <10 <10 <10 31 201114450 25 Ec/-1 <10 <10 <10 Pa/-1 <10 <10 <10 Sa/-1 <10 <10 <10 <10 Ca/-1 285 <10 <10 <10 An/-4 6.1 x 105 3.8 x 104 1.5 x 104 26 Ec/-1 <10 <10 <10 Pa/-1 < 10 <10 <10 Sa/-1 <10 <10 <10 Ca/-1 <10 <10 <10 An/-4 5.8 x 10^ 1.6 x 104 9.5 x 10J 6 Ec/-1 <10 <10 <10 Pa/-1 <10 <10 <10 Sa/-1 <10 <10 <10 Ca /-1 885 <10 <10 An/-4 9.0 x 105 1.5 x 10' 2.4 x 104 12 Ec/-1 <10 <10 <10 Pa/-1 <10 <10 < 10 Sa/-1 <10 <10 <10 Ca/-1 465 <10 <10 An/-4 3.8 xlO' 8.5 x 103 9.5 x 10 J 14 Ec/-1 <10 <10 <10 Pa/-1 <10 <10 <10 Sa/-1 <10 <10 <10 Ca/-1 475 <10 <10 <10 An/-4 4.6 x 105 5.0 x 10 ^ 8.0 x 103 1 Ec/-1 3.5 x 105 <10 <10 Pa/-1 7.3 x 105 <10 <10 Sa/-1 5.5 x 105 <10 <10 Ca/-1 1.3 x 10^ <10 <10 An/-4 5.0 x 10" 1.2 x 103 3.0 x 103 TNTC: The quantity is too large to count these data, indicating that the dispersed aqueous phase of the emulsion can be buffered to a 32 201114450 JHUHipil The pH at which the preservation system inhibits the growth of microorganisms in the formulation more than in the unbuffered equivalent formulation of the aqueous phase to enhance the overall antimicrobial efficacy of the emulsion. The invention is not limited to the above described and exemplified embodiments, and variations and modifications can be made within the scope of the appended claims. [Simple diagram description] None [Main component symbol description] None 33

Claims (1)

201114450 VII. Scope of Application: L. A topical preparation for inhibiting the growth of microorganisms, comprising an effective insecticide dissolved in (4) a towel and an aqueous phase, said water-miscible or water-soluble surfactant, suspending agent and rotor a surfactant, and the aqueous phase comprises one or more preservatives, wherein the aqueous phase is buffered to a pH at which the formulation inhibits microbial growth by an amount greater than the aqueous phase The equivalent formulation of the buffer is large. The topical preparation of claim 1, wherein the killing agent comprises avermectin. Azinc, such as: the topical preparation described in the scope of claim 2, wherein the cytocin is ivermectin, doramectin d〇rameCtm, sdamectm or Abamectin, or a combination thereof. The local preparation according to the second aspect of the patent application, wherein the "the insecticide further includes Spin〇Syn. 5_" Topical preparation, D, from: group consisting of: Sbynoxin factors A, B, C, u E, F, G, H, J, K, L, M, N, 〇, P, n are U, V, W and Υ, or a combination thereof Q, R, S, T, 6. For example, the i-PH value of the patent application range is from about 4.5 to about 6.2. 7. The scope of application of the first aqueous phase is to include citric acid. And/or a lemon according to the above-mentioned item, wherein the topical preparation described in the item, wherein the sodium citrate buffer is buffered. Wherein the aqueous phase comprises from about 1% to about 0.1% citric acid and from about 1.0% to about 125% sodium citrate, based on the weight of 34 201114450 %I]. "9" as claimed The topical preparation according to Item 1, wherein the suspension comprises an oil of eucalyptus oil, shea butter or a combination thereof. The topical preparation of claim 1, wherein the nonionic interface activity comprises oleyl alcohol, wool, sorbitan tristearate or a combination thereof. The topical formulation of claim 3, wherein the water or water-soluble surfactant comprises a polysorbate (10), cetyl acetate, acetaminophen, or a combination thereof. 12. The topical formulation of claim 1, wherein the insecticide comprises ivermectin at a concentration of from about 0.1% to about 1% by weight of the formulation. 13. The topical formulation of claim 4, wherein the pesticide comprises a combined concentration of from about 1% to about 5% of ivermectin and is smothered by weight of the formulation. (Spin〇sad). The topical formulation of claim 1, wherein the oil phase comprises from 20% to 35% of the suspending agent, by weight of the formulation. 15. The topical formulation of claim 1, wherein the oil phase comprises from 10% to 2% by weight of the formulation of the water-miscible or water-soluble surfactant. 16. The topical formulation of claim 1, wherein the oil phase comprises from 15% to 45% by weight of the formulation of the nonionic surfactant. The topical preparation of claim 9, wherein the suspending agent comprises from 25% to 28% by weight of the preparation of olive oil, and up to 5% by weight of the preparation. Avocado oil. 18. The topical formulation of claim 1, wherein the preservative comprises methyl p-hydroxybenzoate at a combined concentration of from 1% to 2% per hydrazine, based on the weight of the formulation. Propyl p-hydroxybenzoate. 19. The topical formulation of claim 1, further comprising a conditioning agent. The topical formulation of claim 19, wherein the conditioning agent comprises cyclomethicone at a concentration of 1% by weight of the formulation. 21. A method of enhancing the resistance of an emulsion to microbial growth, comprising buffering an aqueous phase of the emulsion to a value at which the sheath inhibits microbial growth by a greater amount than the aqueous phase The equivalent formulation without buffer is large. 22. The method of claim 21, wherein the preparation is a preparation as described in claim 1 of the patent application. The method of claim 21, wherein the pH is from about 4.5 to about 6.2. The method of claim 21, wherein the guide and the 7 phase are buffered by an effective amount of citric acid and/or sodium citrate. The method described in claim 24, wherein the method is in the range of $A Y. The aqueous phase comprises from about 0.01% to about 0.1% by weight. Citric acid 2 is from about 1% to about U5% sodium citrate. The method of claim 23, wherein the emulsion comprises ivermectin and the pH inhibits the ivermectin isomerization. 27. A method for treating a subject by a susceptible or anti-therapeutic head lice, wherein the method comprises the step of administering the effective amount of the health of the individual, as described in claim 1 of the patent scope. , the duration - is sufficient to treat the time of the head lice infection. 28. The method of claim 27, wherein the individual is administered a single dose of the formulation to the individual. The method of claim 27, wherein the time # is again from about 1 minute to about 6 minutes. = The method of claim 2, which comprises the topical administration of 2, 3 or 4 doses to the individual, wherein the interval between administrations is 5 to 9 days. 31. The topical preparation as described in the application of the patent item i is an emulsion suitable for topical administration. VIII. 32. The emulsion as described in claim 31 of the patent application includes a water-in-oil emulsion. 33. The insecticide according to claim 32, wherein the insecticide is dissolved in the oil phase of the water-in-oil emulsion, wherein the emulsion is as described in the scope of claim Including an oil-in-water emulsion. The tincture, wherein the insecticide is dissolved in the oil phase of the oil-in-water emulsion (9), wherein 37 201114450 J^UHipiI 4. Designation of representative drawings: (1) Designated representative figure of the case: None (2) Simple description of the symbol of the representative figure: No. 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: No 201114450 Correction Date: July 19, 1999 - No. 10133 Chinese manual without line correction page〇 Especially good for the pH of human skin. Buffers capable of buffering the aqueous phase to a pH between about 45 and about 6.2 are extremely common and readily identifiable to those skilled in the art. Such buffers include, for example, a naphthate buffer, an acetate buffer, a salt buffer, a tartrate buffer, an anti-succinate buffer, a methyl glutarate buffer, and a s-salt salt. Buffering agent, phthalic acid squirting agent, cis-tenic acid granules and mixtures thereof. Preferably, the agent comprises a biologically acceptable decanoate capable of buffering the aqueous phase of the emulsion, non-limiting examples of which are described in the foregoing list. The combination of citric acid and citric acid is preferred. The pH adjusting agent may be directly added by a solid mixing needle or may be added as a part of a liquid or solid buffer comprising a plurality of reagents. In some g-forms, a bar-like acid comprising about 1 to about 〇, 1% by weight, and preferably about 5% by weight, based on the weight of the formulation, is produced. At one nt, the concentration of the citric acid is combined with the weight of the formulation. / 彼J 〇 / ° to about 1,25% by weight sodium citrate, preferably about (10) 9 weight two ^ nano. The amount of nucleic acid and/or sodium citrate may vary depending on the intended value of the preparation. In a particularly preferred embodiment, a combination of about 5% by weight of 055% by weight, (10) 9% by weight, or about 1.1% by weight of citrate can provide antimicrobial activity independent of the preservative, in m-form. , 'can be used instead of a separate preservative. Monthly/Wars and/or sodium monohydrogenate and sodium dihydrogen phosphate can also be used in combination with citric acid and /3⁄4. Other suitable buffers include those comprising acetic acid and/or sodium acetate. In some cases, 'when avermectin is used as a therapeutically active ingredient, 17 201114450 is the Chinese manual of No. 99110133. There is no scribe correction page. The date of July 19, 1999 buffer can also be used to prevent Avi. The bacteriocin is isomerized to the 2_epimer. Other suitable preservatives include sodium benzoate, imidazolidinyl urea (such as the GERMALL preservative family, including GERMALLPLUS), sequestering agents (such as ethylenediamine tetraacetic), either alone or in combination with the free acid. Add, EDTA)) and related compounds at various stages of protonation, as well as citric acid and its sodium salt. Other suitable preservatives present in the formulation may be at a concentration ranging from about 0.01% to 2%, or from about 0.01% to about 5% by weight (e.g., 0.05% by weight), for example, from about 0.01% to about 2%. ). Humectant In some aspects, the formulation may further comprise a humectant. Humectants are hygroscopic materials intended to prevent the formulation from drying out during use and before being washed away from the skin, hair or scalp. Humectants can also act as moisturizers in shampoo and conditioner formulations. The humectant is generally a molecule having a number of hydrophilic groups such as a hydroxyl group, an amine, a carboxylic acid group and an ester thereof which enables the molecule to form a hydrogen bond with water molecules. In some aspects, the other components of the formulation have the dual function of acting as a humectant, such as many nonionic surfactants, including but not limited to oleyl alcohol lanolin alcohol, acetylated lanolin alcohol, and the like. . In another embodiment, the humectant is selected from the group consisting of glycerin, triacetin, sorbitol, xylitol, maltitol, polydextrose, quillaia, lactic acid, urea, and the like, and mixture. The water is dissolved with a therapeutically active ingredient, a suspending agent, a solubilizing agent, and a non-ionic interface. 18 201114450 The micro-growth of the growth enhances the pH of the emulsion. At the pH value, the type of the storage system inhibits the organism from being unbuffered than the aqueous phase. The overall anti-microbial effect of the equivalent sword. The present invention is not limited to the above described and exemplified embodiments, and can be modified and modified within the scope of the appended claims and equivalents. None [Main component symbol description] None 33 201114450 The Chinese patent scope of No. 99110133 is not underlined. Amendment date: July 19, 1999. VII. Patent application scope: 1. A topical preparation for inhibiting the growth of microorganisms, which comprises an effective amount of an insecticide dissolved in oil. In the phase and the aqueous phase, the oil phase comprises water miscible or water; a gluten surfactant, a suspending agent and a nonionic surfactant, and the aqueous phase comprises one or more preservatives, wherein the aqueous phase Buffered to a pH at which the amount of microbial growth inhibited by the formulation is greater than the equivalent formulation of the unbuffered aqueous phase. 2. The topical preparation of claim 1, wherein the insecticide comprises avermectin. Jin ^ 3. The topical preparation according to item 2 of the patent application, wherein avermectin is ivermectin, dora+, (dommectin), serracin (selamectin) or bismuth (abamectin) ), or a combination thereof. 4. The topical insecticide as described in item 2 of the patent application scope further includes nunoxin ( _ (Ning). 5. The partial remedy as described in item 4 of the patent application scope, Sbynosin is selected from the group consisting of: Sbynosin, eight escapes D, E, F, G, H, j, K, L, M, N, 〇, p A, B, C, u, v , w and γ, or a combination thereof. y R, S, T, wherein: 6. The local pH as described in the application for full-time enclosure i is from about 4.5 to about 6.2. 7. If the application of the special Wei Wei Di Xiang Wei part of the aqueous phase is to include the citric acid and / or lemon - as described in the patent application, as described in item 7 of the scope of the topic, which is 34 201114450 Amendment period: July 19, 1999, 0.01% to approximately 〇.1% citric acid is the Chinese patent scope of @10133__^^ The weight of the preparation ΐ5's escaped water phase includes about 1.0% Up to about 1.25% sodium citrate. The topical preparation of claim 1, wherein the suspension comprises eucalyptus oil, shea butter or a combination thereof. 10. The topical preparation of claim i, wherein the nonionic interfacial phlegm, wool, dehydrated (tetra) stearate or a combination thereof. π fresh one, which is 80, acetic acid The topical preparation as described in claim 1, wherein the water-miscible or water-soluble surfactant comprises polysorbate cetyl ester, acetylated lanolin alcohol, or a combination thereof. 12. The topical formulation of the i-th summary, wherein the insecticide comprises ivermectin at a concentration of 1%, by weight of the formulation. ./. The topical preparation of claim 4, wherein the insecticide comprises ivermectin and spines at a combined concentration of about 5% by weight of the formulation. The topical preparation of the invention of claim 5, wherein the oil phase comprises from 2% to 35% by weight of the formulation. 15. The topical formulation of claim 1, wherein the oil phase comprises from 1% to 2% by weight of the formulation of the water-miscible or water-soluble surfactant. / / 16. The topical formulation of claim 1, wherein the oil phase comprises from 15% to 45% by weight of the formulation of the nonionic surfactant. 35 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 The weighting is from 25% to 28% by weight of the plucking oil, and from 1% to 5% by weight of the formulation of shea butter. The topical preparation of claim 1, wherein the preservative comprises a combined concentration of up to 2% of methyl p-hydroxybenzoate and propyl p-hydroxybenzoate, based on the weight of the formulation. 19. The topical preparation of claim 1, wherein the bean further comprises a conditioning agent. , 20. The topical formulation of claim 19, wherein the conditioning agent comprises cyclomethicone at a concentration of from 1% to 5% by weight of the system. 21. If the local gamma described in the __丨 item is used, the topical preparation is an emulsion suitable for topical administration. 22. The emulsions described in claim 21 include water-in-oil emulsions. I d >, A 2 on the application of full-time _22 described in the local _, said killing agent is dissolved in the oil phase of the water-in-oil emulsion. , and 24. The emulsions described in claim 21 include oil-in-water emulsions. The elixirs are as described in claim 1, wherein the insecticide is dissolved in the oil phase of the oil-in-water emulsion. 'A method for enhancing the growth of microorganisms by augmenting the emulsion to buffer the aqueous phase of the emulsion to a certain pH value, the method of which comprises the preparation of the shaft-making micro-small material. 36 201114450 Revision date: 99 years 7 On the 19th of the month, the scope of the Chinese patent of $110133 was corrected without a scribe. 27. The method of claim 5, wherein the preparation is a preparation as described in claim 2 of the patent application. 28. The method of claim 26, wherein the pH is from about 4.5 to about 6.2. The method of claim 26, wherein the aqueous phase of the emulsion is buffered with an effective amount of citric acid and/or sodium citrate. The method of claim 29, wherein the aqueous phase comprises about 0.01% simple 0.1%# citric acid and about 1% to about 1.25% lemon by weight of the formulation. Sodium. The method of claim 28, wherein the milk comprises ivermectin and the pH inhibits the catalysis of the Ivermella. a topical preparation, which is dissolved in the oil phase and the aqueous phase in the treatment of the individual's body. The oil phase includes water mixed with water and a nonionic surfactant, a certain PH# or a humic agent. Wherein the aqueous phase is buffered to a level that is greater than the aqueous phase; the agent inhibits the growth of the microorganisms. 34. The individual is administered to the individual for about 1 minute to ° ^ as in the 32nd paragraph of the patent application. Its #includes 5. The partial system described in item 32 of the patent application scope. 37 Revision date: July 19, 1999, 19, 2011, 144, 00, 00, 00, 00, 00, 00, 00, 00, 00, 00 The preparation is administered in two, three or four doses, wherein the time interval between each administration is from 5 to 9 days.