WO2013000143A1 - 免洗迅速灭毒制剂 - Google Patents
免洗迅速灭毒制剂 Download PDFInfo
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- WO2013000143A1 WO2013000143A1 PCT/CN2011/076628 CN2011076628W WO2013000143A1 WO 2013000143 A1 WO2013000143 A1 WO 2013000143A1 CN 2011076628 W CN2011076628 W CN 2011076628W WO 2013000143 A1 WO2013000143 A1 WO 2013000143A1
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/02—Acyclic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/23—Sulfur; Selenium; Tellurium; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/24—Phosphorous; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
Definitions
- the invention relates to a brand-new product which can quickly kill germ-inactivated virus and can be used for washing and cleaning skin. Specifically, it is a kind of virus which does not need water washing, rapidly inactivates skin surface by increasing ionic strength and quickly kills A no-clean hand cleaner for germs. Background technique
- the infection of the germ virus causes serious damage to human health.
- various antibiotics are produced, and the speed of antibiotic development cannot keep up with the speed of mutation.
- the bacteria in order to adapt to the environment to survive the result of constant variability leads to any superbug that cannot be controlled by any antibiotic, and this superbug is a genetic gene that can be transmitted, that is, in theory, any kind of germ It is possible to become a superbug.
- Once infected it will be completely dependent on human immunity, thus causing global panic.
- the virus because it relies on the body of the infected object to breed, once it enters the human body, the drug removal virus is very harmful to the human body. Therefore, the virus is a big challenge in front of human beings. Prevention of viral infections is further recognized as the most effective and reliable means of combating infectious diseases.
- the oxidative stress window theory provides a new way to quickly inactivate the virus without stimulating the skin.
- the high levels of oxidative stress formed by many substances are fatal to pathogenic viruses, etc.
- the protective effect of the stratum corneum on the surface of human skin makes such an environment with high levels of oxidative stress and has no shadow on human skin.
- to. 1985 Reference: Ji l Amaschinein, James L Hartley. Focus, 1985, Vol 7, No 4, 1-2
- human studies have found that microbial genetic material RNA or DNA in the presence of sodium acetate, ie At a certain ionic strength (higher oxidative stress level), denaturing precipitation occurs under the action of ethanol.
- RNA or DNA This method has become a classic method for extracting microbial genetic material RNA or DNA in textbooks.
- Ethanol has a suitable volatility, and because there is a layer of stratum corneum on the skin of the human hand, ethanol does not easily penetrate the stratum corneum of the skin into the active skin cells. The stimulating effect on the skin is in an acceptable range, and it also kills most germs. And the ability to inactivate some viruses, ethanol is generally used as the main ingredient in disposable cleansing products.
- the virus is generally classified into an enveloped virus and a non-enveloped virus.
- the outer shell of the enveloped virus is covered by a lipid bilayer membrane of a layer of protein, and the outer membrane is similar to the pathogen and is easily destroyed.
- the poliovirus and the like are non-enveloped viruses, and the inactivation rate using simple ethanol is very slow, and the use of ethanol alone cannot effectively inactivate some deadly viruses.
- a first object of the present invention is to obtain a leave-on sterilization composition capable of quickly and effectively killing germs and inactivating viruses without causing damage to the skin of the hand.
- a second object of the present invention is to obtain a leave-on sterilization preparation which is capable of quickly and effectively killing germs and inactivating viruses without causing damage to the skin of the hand.
- a third object of the present invention is to provide a method for preparing a leave-on sterilization preparation which is capable of quickly and effectively killing germs and inactivating viruses without causing damage to the skin of the hand.
- a leave-free rapid anti-toxic formulation composition comprising the following weight components:
- composition system 0.1 to 5 parts by weight of ions for increasing the ionic strength of the composition system;
- the ion parts by weight of 0. 1 ⁇ 1 parts by weight.
- the ion for increasing the ionic strength of the composition system is a monovalent ion, a divalent ion, a trivalent ion or a combination thereof, preferably a divalent ion or a trivalent ion, more preferably a trivalent ion.
- the ion is a monovalent cation, a monovalent anion, a divalent cation, a divalent anion, a trivalent cation, a trivalent anion or a combination thereof.
- the monovalent cation is sodium ion, potassium ion, ammonium ion or a combination thereof;
- the divalent cation is an alkaline earth metal ion, or a transition metal ion;
- the trivalent cation is a cerium ion, a cerium ion, or a cerium ion;
- the monovalent anion is a monovalent halogen anion, a monovalent oxygen-containing anion, or a monovalent organic ion;
- the divalent anion is a sulfate ion, a carbonate ion, or a diacid ion;
- the trivalent anion is a phosphate ion.
- the ion is a phosphate ion.
- the ionic strength of the composition system is between 16 and 500 mM
- the volatile alcohol is selected from the group consisting of ethanol, propanol, butanol, or a combination thereof.
- the ions are present in the form of soluble salts of the ions in water, or in an alcoholic solvent.
- a second aspect of the invention provides a formulation made from the composition of the invention.
- a third aspect of the invention provides a method of preparing a formulation of the invention, comprising the steps of:
- ions for increasing the ionic strength of the composition system are mixed with the volatile alcohol; the ions are present in the form of soluble salts of the ions in water or an alcohol solvent. .
- the ion is present in the form of a soluble salt of the ion in water or an alcohol solvent.
- the acid corresponding to the soluble salt may first be dissolved in water, and then the corresponding base is added to form the soluble salt for further subsequent steps. For example, an aqueous solution of the salt and an alcohol are mixed.
- the inventors have conducted extensive and intensive research to obtain a disposable sterilized product which can quickly and effectively kill germs and inactivate viruses without causing damage to the skin of the hand, and unexpectedly finds that it is specific. Its performance is particularly excellent at ionic strength.
- the present invention has been completed on this basis.
- the invention discloses a novel preparation for quickly killing germs and rapidly inactivating viruses, which does not contain small molecules of aldehydes, halogens, peroxides, antibiotics and antiviral drugs, and stimulates human skin. There is essentially no sex, and this preparation can be used to directly clean human skin without washing with water.
- wash-free means that the formulation is not irritating and toxic to human skin and therefore does not require washing.
- the "no irritation and toxicity to human skin” can be found in the skin irritation test in the examples.
- the "pathogen” includes an enveloped virus and a non-enveloped virus.
- Representative ions of the enveloped virus include, but are not limited to, herpes zoster virus, influenza virus, and HIV, etc.
- Representative examples of non-enveloped viruses include, but are not limited to, poliovirus, hepatitis A virus, hand, foot and mouth virus, and the like. Among them, poliovirus is the most difficult representative of inactivated virus, so the research test for inactivating virus ability is based on inactivation of poliovirus.
- rapid anti-virus means that the inactivation rate reaches 19.99% within 1 minute, that is, the logarithm value 4.
- a leave-free rapid anti-toxic formulation composition comprising the following weight components:
- composition system 0.1 to 5 parts by weight of ions for increasing the ionic strength of the composition system;
- the remaining components are water. 1 ⁇ 1 ⁇
- the ion parts by weight of 0. 1 ⁇ 1 parts by weight.
- Ethanol is a commonly used disposable hand cleaner, but it does not rapidly inactivate the virus, and is essentially ineffective against many common viruses such as hand, foot and mouth virus, poliovirus, and the like.
- the present inventors have found that a small molecule of alcohol can be used as a carrier to increase the ion concentration in the solution (increasing the ionic strength, that is, to increase the level of oxidative stress), thereby achieving rapid and effective killing of the pathogen and inactivation of the virus while not occupying the part.
- the effect of skin damage When the ion concentration is too low, the purpose of increasing the ionic strength cannot be achieved, thereby reducing the rate of killing the germ and inactivating the virus; when the ion concentration is too high, it will cause damage to human skin.
- the present invention does not employ specific reactive ions, but rather increases the ionic strength by using ions to achieve a high level of oxidative stress that is lethal to microorganisms including viruses.
- the present invention is the first in the world to provide a means and product for rapidly inactivating viruses by increasing the level of oxidative stress. Ions that increase the ionic strength of the composition system
- the ions of the present invention which increase the ionic strength of the composition system increase the level of oxidative stress by increasing the ionic strength of the composition system.
- the ion for increasing the ionic strength of the composition system is a monovalent ion, a divalent ion, a trivalent ion or a combination thereof, preferably a divalent ion or a trivalent ion, Trivalent ions are preferred.
- the ion is a monovalent cation, a monovalent anion, a divalent cation, a divalent anion, a trivalent cation, a trivalent anion or a combination thereof.
- ions for increasing the level of oxidative stress and killing the virus inactivated virus include all ions which are not irritating and toxic to human skin, including monovalent ions, divalent ions, and trivalent ions. ion. Since the amount of high-valent ion pair required to enhance the equivalent ionic strength is smaller than that of the low-valent ion, a high-valent ion is preferred.
- the ions used in the present invention may be cationic, including all ions that are stable and do not stimulate human skin.
- Monovalent cations include, but are not limited to, sodium ions, potassium ions, ammonium ions, and the like.
- Divalent cations include, but are not limited to, alkaline earth metal ions such as calcium ions, magnesium ions, transition metal ions such as zinc ions, iron ions, copper ions, and the like.
- Trivalent cations include, but are not limited to, cerium ions, cerium ions, cerium ions, and the like.
- the monovalent ion is a monovalent halogen anion such as chloride ion, a monovalent oxygen-containing anion such as an inorganic nitrate ion, a monovalent organic ion such as a formate ion, an acetate ion, a propionate ion or the like.
- Divalent anions include, but are not limited to, sulfate ions, carbonate ions, diacids such as succinate ions, and the like.
- Trivalent anions include, but are not limited to, phosphate ions and the like.
- the ions used in the present invention may be anions including all ions that are stable and do not stimulate human skin.
- Monovalent ions include, but are not limited to, monovalent halogen anions such as chloride ions, monovalent oxygenated anions such as inorganic nitrate ions, monovalent organic ions such as formate ions, acetate ions, propionate ions, and the like.
- the divalent anion includes, but is not limited to, a sulfate ion, a carbonate ion, a diacid such as a succinate ion, and the like.
- Trivalent anions include, but are not limited to, phosphate ions, and the like.
- the monovalent cation is sodium ion, potassium ion, ammonium ion or a combination thereof;
- the divalent cation is an alkaline earth metal ion, or a transition metal ion;
- the trivalent cation is a cerium ion, a cerium ion, or a cerium ion;
- the monovalent anion is a monovalent halogen anion, a monovalent oxygen-containing anion, or a monovalent organic ion;
- the divalent anion is a sulfate ion, a carbonate ion, or a diacid ion;
- the trivalent anion is a phosphate ion.
- the preferred high-valent ions of the present invention are phosphate ions, which are both high-valent ions and It is oxidizing and safe for the skin.
- High-priced metal ions generally have strong oxidizing properties, so they are not preferred.
- the ion is a phosphate ion.
- the ionic strength of the composition system is between 16 and 500 mM.
- the ions are present in the form of the ions in water, or alcohol. Soluble salts in solvent-like solvents.
- the ion parts by weight of 0. 1 ⁇ 1 parts by weight.
- the weight to volume ratio is the ratio of the weight of the ions to the volume of the composition system.
- the weight to volume ratio of ions in the product is, for example,
- the carrier of the product disclosed in the present invention is a small molecule alcohol having good volatility, preferably ethanol and isopropanol.
- the preferably volatile small molecule alcohol may be a C2 to C4 lower alcohol.
- the volatile alcohol is selected from the group consisting of ethanol, propanol, butanol, or a combination thereof.
- the amount of the alcohol is between 50 and 99 parts by weight. If calculated as a percentage by weight, it may be between 50% and 99% by weight, based on the total weight of the composition.
- the present invention provides a formulation made from the composition of the present invention.
- the invention can be made into a fluid dosage form product, and the aerosol product can also be made into a gel type product as long as it does not affect the efficacy of the product.
- the preparation method of the preparation of the invention comprises the following steps:
- ions for increasing the ionic strength of the composition system are mixed with the volatile alcohol; the ions are present in the form of soluble salts of the ions in water or an alcohol solvent. .
- the ions are present in the form of soluble salts of the ions in water, or in an alcoholic solvent.
- the acid corresponding to the soluble salt may first be dissolved in water, and then the corresponding base is added to form the soluble salt for further subsequent steps.
- an aqueous solution of the salt and an alcohol are mixed.
- the poliovirus is the most difficult representative of inactivated viruses, so the study of the ability to inactivate viruses is based on the inactivation of poliovirus.
- the examples are exemplified by three products, which are monovalent salts such as sodium acetate; divalent salts such as copper acetate; and trivalent salts such as sodium phosphate.
- the preparation method comprises the following steps: first dissolving the used acid in water, then adding an equivalent amount of a base such as sodium hydroxide or ammonia water, controlling the pH to not less than 3, mixing uniformly, cooling to room temperature, and then uniformly mixing with 95% of the alcohol.
- the final salt content is 0. 6+0. 2%, the formula is as follows:
- samples 1 to 10 correspond to Examples 1 to 10, respectively.
- the above examples increase the ionic strength by means of increasing the ion concentration, thereby causing a high level of oxidative stress to microorganisms.
- Samples 1, 2 use monovalent ions, ie acetate ions and sodium ions; samples 3, 4 are still monovalent ions, but cations are replaced with non-metal ions; the cations in samples 5, 6 are divalent ions; In samples 7, 8, 9, 10, trivalent ions were used.
- the components and concentrations of the neutralizing agent are: 5% sodium thiosulfate, 3. 0% Tween-80, 3 g/L lecithin PBS (phosphate buffer). 3% bovine serum albumin organic interfering substance, TSA (soybean trypsin) medium.
- the test temperature was 20 ° C ⁇ 1, and was repeated 3 times, and the result was an average value.
- the neutralizer was first tested and it was found that the neutralizer solution and the neutralized product solution did not affect the growth of E. coli.
- the efficacy test for killing E. coli was tested for 0.5 minutes, 1. 0 minutes, and 1.5 minutes, and the killing values were all greater than 5
- the components and concentrations of the neutralizing agent were: 5% sodium thiosulfate, 3. 0% Tween-80, and 3 g/L lecithin in PBS. 3% bovine serum albumin organic interfering substance, TSA medium.
- the test temperature was 20 ° C ⁇ 1, and was repeated 3 times, and the results were average values.
- the efficacy test for killing Staphylococcus aureus was tested at 0.5 min, 1. 0 min, and 1.5 min, respectively, and the kill log values were all greater than 5.
- Candida albicans ATCC10231 the components and concentrations of the neutralizer were: 5% sodium thiosulfate, 3. 0% Tween-80, and 3 g/L lecithin in PBS. 3% bovine serum albumin organic interfering substance, TSA medium. The test temperature was 20 ° C ⁇ 1, and was repeated 3 times, and the results were average values.
- the efficacy test for killing Staphylococcus aureus was tested at 0.5 min, 1. 0 min, 1. 5 min, and the kill log values were all greater than 4
- poliovirus type 1 vaccine strain, disinfection testing center of the Chinese Academy of Military Medical Sciences
- host cell VER0 cells Disinfection Testing Center of the Chinese Academy of Military Medical Sciences
- neutralizers For: 3. 0% Tween-80, 3g/L lecithin in PBS. 3% of bovine serum albumin organic interfering substances. The test temperature was 20 ° C ⁇ 1, and was repeated 3 times, and the results were average values.
- the virus suspension has a titer of 10 7 -10 8 TCID 5 .
- the PV-1 virus suspension was diluted with 3% of bovine serum albumin organic interference material, and it was found that the neutralizer solution and the neutralized product solution did not affect the activity of the poliovirus.
- the efficacy test for inactivating poliovirus was tested at 0.5 min, 1. 0 min, 1. 5 min, and the kill log values were all greater than 4
- Acute oral toxicity test in mice oral LD 5 . >5000mg/kg body weight, the toxicity rating is actually non-toxic.
- the toxic solution was prepared to be 300 mg/ml, and the infected volume was 0. 2 ml/10 g body weight once. The observation period was 14 days, and the animals showed no abnormalities, and no animals died.
- mice There are 50 Kunming outbred mice in Switzerland, half female, weighing 25-30g, animal room temperature 25 ° C, relative humidity 50%. Cyclophosphamide (CP) was used as a positive control. The test animals were set up in 3 dose groups, 5000, 2000, and 500 mg/kg body weight, and the positive control group was 40 mg/kg cyclophosphamide. Another negative control group was set up. 10 mice per group, half female.
- CP Cyclophosphamide
- the preparation of the drug is 5, 2, 0.5 g, respectively, adding distilled water to 20 ml, cyclophosphamide 20 mg plus physiological saline to 5 ml. Animals were exposed to oral administration for 30 hours, two doses were given 24 hours, and the second dose was taken 6 hours.
- the volume of the infection was 0. 2ml/10g body weight, and cyclophosphamide was intraperitoneally injected, 0, lml/10g body weight.
- the cervical vertebrae dislocation method kills the mouse, takes one side of the femur, removes the muscles, wipes the blood stains, and cuts the ends of the femur to expose the marrow cavity. The syringe was aspirated with 0.
- Subacute toxicity test No harmful dose (NOAEL) was observed at 1000 mg/kg body weight. There were 40 Wi star grade rats, 6-8 weeks old, half female, weighing 180-220 g, animal room temperature 25 ° C, relative humidity 50%. The test group consisted of 3 groups at doses of 1000, 500, 250 mg/kg body weight, and control group. The test solution was 25, 12. 5, and 6.25 g, and distilled water was added to 250 ml. Rats were inoculated with lml/100g body weight, and given the same amount of distilled water, they were exposed once a day for 28 days. Weigh once a week and adjust the dose according to the weight.
- the indicators were tested 24 h after the last exposure, and then the rats were sacrificed for histopathological examination.
- the blood analysis items are total red blood cells, total white blood cells, hematocrit, hemoglobin content, and total number of platelets; blood biochemical tests include AST, ALT, B ring, TP, ALB, GLU, CH0; organ weight measurement liver, kidney weight, and calculation Organ weight coefficient; pathology includes all internal organs.
- the novel product disclosed by the invention can quickly kill germs, fungi, and rapidly inactivate the virus, and at the same time, the product is not irritating to the skin and has no toxicity to the body.
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Abstract
一种免洗迅速灭毒制剂组合物,所述组合物包括以下重量组分:50〜99重量份的C2〜C4挥发性醇;0.01〜5重量份用于提高组合物体系离子强度的离子;其余组分是水。该免洗迅速灭毒制剂组合物通过升高离子强度从而提高化应激水平,从而达到免洗迅速灭毒的效果。
Description
免洗迅速灭毒制剂 技术领域
本发明涉及一种全新的迅速杀死病菌灭活病毒、可以用于免洗清洁皮肤的产 品, 具体的说, 是一种不需要水洗、 通过提高离子强度迅速灭活皮肤表面病毒和 迅速杀死病菌的一种免洗洁手产品。 背景技术
病菌病毒的感染对人类的健康造成严重的损害。 当前, 由于抗生素的滥用, 导致各种抗药菌的产生, 抗生素开发速度无法赶上病菌的变异速度。 同时, 由于 环境的严重污染, 病菌为了适应环境生存, 不断变异的结果导致任何抗生素都无 法控制的超级菌, 并且这种超级菌是可以传递的遗传基因, 即理论上说, 任何一 种病菌都有可能成为超级菌, 一旦感染, 将完全依赖于人类自身的免疫能力, 因 此造成全球的恐慌。 而病毒, 因为是依靠被感染客体的机体进行繁殖, 一旦进入 人体, 药物清除病毒对人体的伤害很大, 所以, 病毒更是摆在人类面前的一大挑 战。 预防病毒病菌感染, 人们进一步认识到是对抗传染病的最有效和可靠手段。
许多病菌病毒能够在人类的手表面存活长达几个小时。(参考文献 1 : Mbi thi JN, Springthorpe VS,等, Survival of hepati ti s A virus on human hands and i ts transfer on contact wi th animate and inanimate surfaces. J Cl in Microbiol 1992 ; 30 : 757-763 (肝炎 A病毒在人手上的存活期以及它们在活性及无 活性表面上的传染, 临床微生物学杂志, 1992年, 第 30期, 757-763页)。 参考 文献 2: Schurmann W, Eggers HJ. An experimental study on the epidemiology of enteroviruses: water and soap washing of pol iovirus type
1- contaminated hands, i ts effectiveness and kinetics. Med Microbiol Immunol 1985 ; 174 : 221-236) (肠道病毒传染性实验: 水和肥皂洗涤脊椎灰质炎 病毒污染手的功效性和动力学研究, 医药微生物免疫学, 1985年, 第 174期, 221-236页)
"病从口入"是很多传染病最主要的感染方式, 世界卫生组织 (WHO)、 美国 FDA和疾控中心(CDC)、 中国疾控中心等权威部门, 均明确指出, 清洁双手是切 断传播途径的最重要方法。除了传统的易感染区域例如医院环境外, 随着全球化 的不断深化,奔波在旅途中的人员迅速增加,清洁洗手用水难以得到保障。同时,
由于环境的污染导致病毒病菌的变异, 它们的致病性、甚至于致命性的破坏力迅 速增强, 最近几年的 SARS、 禽流感、 手足口病、 等等, 逐步明显。
市场上迄今为止还没有能够快速灭活病毒、 又不剌激皮肤的产品。 首先, 传 统的醛类(如戊二醛、 等)、 卤素类(如漂白粉、 碘酒、 等)、 及过氧化物(如双氧 水、 等)类等有效成分可以快速灭活致命性病毒, 例如脊椎灰质炎病毒, 但是, 这些有效成分对皮肤的剌激性很大, 无法用于免洗洁手产品。 其次, 人类合成的 各种灭活病毒的药物, 由于成本高昂、 对人体细胞危害大、 又会造成抗药性, 同 样无法用于皮肤的免洗灭活病毒。
氧化应激窗口期理论为快速灭活病毒、又不剌激皮肤提供了一个崭新的途径 。 许多物质形成的高氧化应激水平, 对病菌病毒等是致命的, 但是, 人类皮肤表 面的角质层的保护作用, 使如此高的氧化应激水平的环境, 对人类的皮肤基本没 有任何影口向。 1985年(参考文献: Ji l A Zeugin, James L Hartley. Focus, 1985, Vol 7, No 4, 1-2), 人类的研究发现, 微生物的遗传物质 RNA或 DNA在醋酸钠 的存在下, 即在一定的离子强度下(较高的氧化应激水平), 在乙醇的作用下会发 生变性沉淀, 此方法已经成为教科书中经典的提取微生物遗传物质 RNA或 DNA 的方法。 而乙醇具有合适的挥发性, 并且由于人手皮肤有一层角质层, 乙醇不易 透过皮肤角质层进入活性皮肤细胞, 对皮肤的剌激作用处于可以接受的范围, 并 且又具备杀死绝大多数病菌和灭活部分病毒的能力,乙醇一般用作免洗洁肤产品 的主要成分。病毒一般分为包膜(enveloped)病毒和无包膜(non-enveloped)病毒 。 包膜病毒的核心壳外被一层蛋白质的类脂双层膜覆盖, 外膜和病菌类似, 易于 被破坏。 脊椎灰质炎病毒等是无包膜(non-enveloped)病毒, 使用单纯乙醇的灭 活速度很慢, 单纯使用乙醇无法有效的灭活一些致命性病毒。
所以, 开发能够迅速杀死病菌并灭活所有病毒(全球对迅速灭活病毒的要求 是, 1分钟内, 99. 99%的病毒被灭活, 常表达为对数值为 4)的免水洗手的产品, 是当前人类急需攻克的难关。 因为, 免水洁手的产品必须满足两个基本要求, 一 是能够快速有效的杀死病菌和灭活病毒, 二是不能对手部皮肤造成伤害。
综上所述,本领域缺乏一种能够快速有效的杀死病菌和灭活病毒且不对手部 皮肤造成伤害的免洗杀菌灭病毒制品, 因此, 本领域迫切需要开发此种能够快速 有效的杀死病菌和灭活病毒且不对手部皮肤造成伤害的免洗杀菌灭病毒制品。 发明内容
本发明的第一目的在于获得一种能够快速有效的杀死病菌和灭活病毒且不 对手部皮肤造成伤害的免洗灭菌组合物。
本发明的第二目的在于获得一种能够快速有效的杀死病菌和灭活病毒且不 对手部皮肤造成伤害的免洗灭菌制剂。
本发明的第三目的在于获得一种能够快速有效的杀死病菌和灭活病毒且不 对手部皮肤造成伤害的免洗灭菌制剂的制备方法。 在本发明的第一方面, 提供了一种免洗迅速灭毒制剂组合物, 所述组合物包括 以下重量组分:
50〜99重量份 C2〜C4挥发性醇;
0. 01〜5重量份用于提高组合物体系离子强度的离子;
其余组分为水。 在一优选例中, 所述离子的重量份数为 0. 1〜1重量份。 在本发明的一个具体实施方式中, 所述提高组合物体系离子强度的离子为一价 离子、 二价离子、 三价离子或其组合, 优选二价离子或三价离子, 更优选三价离子
在本发明的一个具体实施方式中, 所述离子是一价阳离子、 一价阴离子、 二价 阳离子、 二价阴离子、 三价阳离子、 三价阴离子或其组合。 在本发明的一个具体实施方式中, 所述一价阳离子为钠离子、 钾离子、 铵离子 或其组合;
所述二价阳离子为碱土金属离子、 或过渡金属离子;
所述三价阳离子为钪离子、 钇离子、 或镧离子;
所述一价阴离子为一价卤素阴离子、 一价含氧负离子、 或一价有机离子; 所述二价阴离子为硫酸根离子、 碳酸根离子、 或双酸根离子;
所述三价阴离子为磷酸根离子。 在本发明的一个具体实施方式中, 所述离子为磷酸根离子。
在本发明的一个具体实施方式中, 所述组合物体系的离子强度为 16-500mM之间
在本发明的一个具体实施方式中, 所述挥发性醇选自乙醇、 丙醇、 丁醇、 或其 组合。 在本发明的一个具体实施方式中, 所述的离子的存在形式为所述离子在水中、 或醇类溶剂中的可溶性盐。 本发明的第二方面提供一种本发明所述的组合物制得的制剂。 本发明的第三方面提供一种本发明所述的制剂的制备方法, 其包括如下步骤:
(a)提供以下 50〜99重量份 C2〜C4挥发性醇;
(b)将 0. 01〜5重量份用于提高组合物体系离子强度的离子与所述挥发性醇混 合; 所述离子的存在形式为所述离子在水中、 或醇类溶剂中的可溶性盐。 在一优选例中, 所述离子的存在形式为所述离子在水中、 或醇类溶剂中的可溶 性盐。 具体地, 可首先将所述可溶性盐对应的酸溶解在水中, 然后加入对应的碱生 成所述可溶性盐, 以用于再进行后续步骤。 例如将所述盐的水溶液和醇混匀。 具体实施方式
本发明人经过广泛而深入的研究, 通过改进制备工艺, 获得了一种能够快 速有效的杀死病菌和灭活病毒且不对手部皮肤造成伤害的免洗灭菌制品,并意外 地发现在特定的离子强度下其性能特别优异。 在此基础上完成了本发明。
本发明揭示了一种全新的快速杀灭病菌、快速灭活病毒的制剂, 这种制剂不 含有小分子的醛、 卤素、 过氧化物、 不含抗生素和抗病毒药物, 对人体皮肤的剌 激性基本没有, 这种制剂可以用于直接清洁人类的皮肤, 且不用水洗涤。
本文中, 所述 "免洗"是指所述制剂对人类皮肤没有剌激性和毒性, 故此无需 洗去。 所述 "对人类皮肤没有剌激性和毒性"可参见实施例中的皮肤剌激性试验。
本文中, 所述 "病菌"包括包膜(enveloped)病毒和无包膜(non-enveloped)
病毒。 包膜病毒的代表离子包括但不限于: 带状疱疹病毒、 流感病毒、 和艾滋病 毒等; 无包膜病毒的代表例子包括但不限于脊椎灰质炎病毒、 甲肝病毒、 手足口 病毒等。 其中脊椎灰质炎病毒是最难灭活病毒的代表, 所以, 灭活病毒能力的研 究测试以灭活脊椎灰质炎病毒为标准。
本文中, 所述 "迅速灭毒"是指 1分钟内灭活率达到 99. 99%, 即对数值 4。 以下对本发明的各个方面进行详述:
免洗迅速灭毒制剂组合物
在本发明的第一方面, 提供了一种免洗迅速灭毒制剂组合物, 所述组合物包括 以下重量组分:
50〜99重量份 C2〜C4挥发性醇;
0. 01〜5重量份用于提高组合物体系离子强度的离子;
其余组分为水。 在一优选例中, 所述离子的重量份数为 0. 1〜1重量份。 乙醇是常用免洗洁手产品, 但是不能快速灭活病毒、 对很多常见病毒如手足口 病毒、 脊椎灰质炎病毒、 等等, 基本无效。
而本发明人发现, 以小分子的醇类为载体, 通过增加溶液中离子浓度(提高离 子强度即提升氧化应激水平)的方法可实现快速有效的杀死病菌和灭活病毒同时 不对手部皮肤造成伤害的效果。 当离子浓度太低时, 无法达到提高离子强度的目 的, 从而降低杀死病菌和灭活病毒的速率; 当离子浓度太高时, 会对人的皮肤带 来损害。
本发明不是采用特定的活性离子, 而是通过使用离子提高离子强度、 达到免洗 洁肤液体可以造成对微生物包括病毒致命的高氧化应激水平。本发明是全球第一个 通过提高氧化应激水平来快速灭活病毒的手段与产品。 提高组合物体系离子强度的离子
本发明的提高组合物体系离子强度的离子通过提高组合物体系离子强度从而提 高氧化应激水平。在本发明的一个具体实施方式中,所述提高组合物体系离子强度 的离子为一价离子、 二价离子、 三价离子或其组合, 优选二价离子或三价离子, 更
优选三价离子。
在本发明的一个具体实施方式中, 所述离子是一价阳离子、 一价阴离子、 二价 阳离子、 二价阴离子、 三价阳离子、 三价阴离子或其组合。
本发明揭示的产品中, 用于提高氧化应激水平、 杀死病菌灭活病毒的离子, 包括所有的对人类皮肤没有剌激性和毒性的离子, 包括一价离子、 二价离子、 三 价离子。 由于高价离子对增强同等离子强度所需的量比低价离子的用量少, 优选 高价离子。 本发明所使用的离子可以是阳离子, 包括所有稳定且不剌激人类皮肤的离子。 一价阳离子包括但不限于钠离子、 钾离子、 铵离子等。
二价阳离子包括但不限于碱土金属离子如钙离子、 镁离子, 过渡金属离子如锌 离子、 铁离子、 铜离子等。
三价阳离子包括但不限于钪离子、 钇离子、 镧离子等。
一价离子为一价卤素阴离子例如氯离子、 一价含氧负离子如无机硝酸根离子、 一价有机离子如甲酸根离子、 醋酸根离子、 丙酸根离子等。
二价阴离子包括但不限于硫酸根离子、 碳酸根离子、 双酸如丁二酸根离子等。 三价阴离子包括但不限于磷酸根离子等。
本发明所使用的离子可以是阴离子, 包括所有稳定且不剌激人类皮肤的离子 。 一价离子, 包括但不限于一价卤素阴离子例如氯离子、一价含氧负离子如无机 硝酸根离子、一价有机离子如甲酸根离子、 醋酸根离子、 丙酸根离子、 等。 二价 阴离子包括但不限于硫酸根离子、 碳酸根离子、 双酸如丁二酸根离子、 等。 三价 阴离子包括但不限于磷酸根离子、 等。 在本发明的一个具体实施方式中, 所述一价阳离子为钠离子、 钾离子、 铵离子 或其组合;
所述二价阳离子为碱土金属离子、 或过渡金属离子;
所述三价阳离子为钪离子、 钇离子、 或镧离子;
所述一价阴离子为一价卤素阴离子、 一价含氧负离子、 或一价有机离子; 所述二价阴离子为硫酸根离子、 碳酸根离子、 或双酸根离子;
所述三价阴离子为磷酸根离子。
需要注意的是, 本发明优选的高价离子为磷酸根离子, 其既是高价离子, 又没
有氧化性, 对皮肤安全。 而高价金属离子一般都具有较强的氧化性, 所以不优选。 因此, 在本发明的一个优选的具体实施方式中, 所述离子为磷酸根离子。 在本发明的一个具体实施方式中, 所述组合物体系的离子强度为 16-500mM之间 在本发明的一个具体实施方式中, 所述的离子的存在形式为所述离子在水中、 或醇类溶剂中的可溶性盐。
在一优选例中, 所述离子的重量份数为 0. 1〜1重量份。
为了方便起见, 也可以采用重量体积比进行投料。所述重量体积比是离子的 重量相对组合物体系的体积的比例。 离子在产品中的重量体积比例如为
0. 01%-5%之间, 优选 0. 1%到 1%之间。 挥发性醇
本发明揭示产品的载体为具有较好挥发性的小分子的醇, 优选乙醇和异丙醇 。 所述较好挥发性的小分子的醇可以是 C2〜C4的低级醇类。 在本发明的一个具 体实施方式中, 所述挥发性醇选自乙醇、 丙醇、 丁醇、 或其组合。
醇的用量介于 50〜99重量份之间。 若以重量百分比计算, 可以是 50重量%-99 重量%之间, 以组合物总重量计算。 制剂及其制备方法
本发明提供一种本发明所述的组合物制得的制剂。 本发明可以做成流体剂型 产品, 气雾剂产品、 也可以做成凝胶型产品, 只要不影响产品的功效即可。 本发明所述的制剂的制备方法包括如下步骤:
(a)提供以下 50〜99重量份 C2〜C4挥发性醇;
(b)将 0. 01〜5重量份用于提高组合物体系离子强度的离子与所述挥发性醇混 合; 所述离子的存在形式为所述离子在水中、 或醇类溶剂中的可溶性盐。 在优选例中, 所述离子的存在形式为所述离子在水中、 或醇类溶剂中的可溶性 盐。 具体地, 可首先将所述可溶性盐对应的酸溶解在水中, 然后加入对应的碱生成 所述可溶性盐, 以用于再进行后续步骤。 例如将所述盐的水溶液和醇混匀。
下面所给出的实施例是为了更好地说明本发明,并不是说本发明所揭示的内 容仅限于下面的实施例。 如无具体说明, 本发明的各种原料均可以通过市售得到; 或根据本领域的常 规方法制备得到。除非另有定义或说明, 本文中所使用的所有专业与科学用语与 本领域技术熟练人员所熟悉的意义相同。此外任何与所记载内容相似或均等的方 法及材料皆可应用于本发明方法中。
本发明的其他方面由于本文的公开内容,对本领域的技术人员而言是显而易 见的。
下面结合具体实施例, 进一步阐述本发明。 应理解, 这些实施例仅用于说明 本发明而不用于限制本发明的范围。 下列实施例中未注明具体条件的实验方法, 通常按照常规条件, 或按照制造厂商所建议的条件进行。 除非另外说明, 否则所 有的份数为重量份, 所有的百分比为重量百分比, 所述的聚合物分子量为数均分 除非另有定义或说明,本文中所使用的所有专业与科学用语与本领域技术熟 练人员所熟悉的意义相同。此外任何与所记载内容相似或均等的方法及材料皆可 应用于本发明方法中。
实施例中涉及的测试方法和标准如下:
中华人民共和国*** 《消毒技术规范》 2002. 11, 第 2. 1. 1. 5. 5条, 和第 2. 1. 1. 7. 4条。 实施例 1〜: 10 : 产品配方
脊椎灰质炎病毒是最难灭活病毒的代表, 所以, 灭活病毒能力的研究测试以 灭活脊椎灰质炎病毒为标准。
实施例以三种产品为例, 分别为一价盐、 如醋酸钠; 二价盐, 如醋酸铜; 三 价盐, 如磷酸钠。 配制方法为先将使用的酸溶解于水中, 然后加入等当量的碱如 氢氧化钠或者氨水, 控制 pH值不小于 3, 混合均匀后, 冷却到室温, 然后再和 95%的醇混合均匀,最后的盐含量为总体积中的重量含量 0. 6+0. 2%,配方如下表:
活性成分 盐的用量 醇用量 产品外观
样品 1 醋酸钠 0. 6% 68%乙醇 透明清液
样品 2 醋酸钠 0. 6% 68%异丙醇 透明清液 样品 3 醋酸铵 0. 6% 68%乙醇 透明清液 样品 4 醋酸铵 0. 6% 68%异丙醇 透明清液 样品 5 醋酸铜 0. 6% 68%乙醇 透明清液 样品 6 醋酸铜 0. 6% 68%异丙醇 透明清液 样品 7 磷酸钠 0. 6% 68%乙醇 透明清液 样品 8 磷酸钠 0. 6% 68%异丙醇 透明清液 样品 9 磷酸钠 0. 6% 58%乙醇 透明清液 样品 10 磷酸钠 0. 6% 58%异丙醇 透明清液 讨论:
上述的样品 1〜10分别对应于实施例 1〜10。上述实施例通过提高离子浓度 的手段提高离子强度、 从而造成对微生物而言很高的氧化应激水平。 样品 1,2 使用一价离子, 即醋酸根离子和钠离子; 样品 3, 4虽然使用的仍然是一价离子, 但是阳离子换为非金属离子; 样品 5, 6中的阳离子是二价离子; 样品 7, 8, 9, 10 中, 使用了三价离子。
而从下面的功效性试验结果显示, 快速杀菌灭活病毒的功效, 随离子的价升
1¾而提! ¾。 杀灭大肠杆菌功效
使用大肠杆菌 8099 (中国人民解放军军事医学科学院消毒检测中心), 中和 剂的组分和浓度为: 5%的硫代硫酸钠、 3. 0%的吐温 -80、 3g/L卵磷脂的 PBS (磷酸 盐缓冲液)。 3%的牛血清蛋白有机干扰物质, TSA (大豆胰蛋白胨)培养基。 试验温 度为 20° C±1, 重复 3次, 结果为平均值。
首先测试中和剂, 发现中和剂溶液和中和产物溶液不影响大肠杆菌的生长。 杀灭大肠杆菌的功效试验, 分别测试了 0. 5分钟、 1. 0分钟、 1. 5分钟, 杀 灭对数值全部大于 5
0. 5分钟 1. 0分钟 1. 5分钟
样品 1 >5. 00 >5. 00 >5. 00
样品 2 >5. 00 >5. 00 >5. 00
样品 3 >5. 00 >5. 00 >5. 00
样品 4 >5. 00 >5. 00 >5. 00
样品 5 >5. 00 >5. 00 >5. 00
样品 6 >5. 00 >5. 00 >5. 00
样品 7 >5. 00 >5. 00 >5. 00
样品 8 >5. 00 >5. 00 >5. 00
样品 9 >5. 00 >5. 00 >5. 00
样品 10 >5. 00 >5. 00 >5. 00 杀灭金黄色葡萄球菌功效
使用金黄色葡萄球菌 ATCC6538 , 中和剂的组分和浓度为: 5%的硫代硫酸钠、 3. 0%的吐温 -80、 3g/L卵磷脂的 PBS。 3%的牛血清蛋白有机干扰物质, TSA培养 基。 试验温度为 20° C±1, 重复 3次, 结果为平均值。
测试发现中和剂溶液和中和产物溶液不影响金黄色葡萄球菌的生长。
杀灭金黄色葡萄球菌的功效试验, 分别测试了 0. 5分钟、 1. 0分钟、 1. 5分 钟, 杀灭对数值全部大于 5。
0. 5分钟 1. 0分钟 1. 5分钟
样品 1 >5. 00 >5. 00 >5. 00
样品 2 >5. 00 >5. 00 >5. 00
样品 3 >5. 00 >5. 00 >5. 00
样品 4 >5. 00 >5. 00 >5. 00
样品 5 >5. 00 >5. 00 >5. 00
样品 6 >5. 00 >5. 00 >5. 00
样品 7 >5. 00 >5. 00 >5. 00
样品 8 >5. 00 >5. 00 >5. 00
样品 9 >5. 00 >5. 00 >5. 00
样品 10 >5. 00 >5. 00 >5. 00 杀灭白色念珠菌功效
使用白色念珠菌 ATCC10231 ,中和剂的组分和浓度为: 5%的硫代硫酸钠、 3. 0% 的吐温 -80、 3g/L卵磷脂的 PBS。 3%的牛血清蛋白有机干扰物质, TSA培养基。 试验温度为 20° C±1, 重复 3次, 结果为平均值。
测试发现中和剂溶液和中和产物溶液不影响金黄色葡萄球菌
(Staphyloccocus aureus Rosenbach)的生长。
杀灭金黄色葡萄球菌的功效试验, 分别测试了 0. 5分钟、 1. 0分钟、 1. 5分 钟, 杀灭对数值全部大于 4
0. 5分钟 1. 0分钟 1. 5分钟
样品 1 >4. 00 >4. 00 >4. 00 样品 2 >4. 00 >4. 00 >4. 00 样品 3 >4. 00 >4. 00 >4. 00 样品 4 >4. 00 >4. 00 >4. 00 样品 5 >4. 00 >4. 00 >4. 00 样品 6 >4. 00 >4. 00 >4. 00 样品 7 >4. 00 >4. 00 >4. 00 样品 8 >4. 00 >4. 00 >4. 00 样品 9 >4. 00 >4. 00 >4. 00 样品 10 >4. 00 >4. 00 >4. 00 灭活脊椎灰质炎病毒功效
使用脊椎灰质炎病毒 1型 (PV-I, 疫苗株, 中国人民解放军军事医学科学院 消毒检测中心), 宿主细胞 VER0细胞(中国人民解放军军事医学科学院消毒检测 中心), 中和剂的组分和浓度为: 3. 0%的吐温 -80、 3g/L卵磷脂的 PBS。 3%的牛血 清蛋白有机干扰物质。 试验温度为 20° C±1, 重复 3次, 结果为平均值。
病毒悬液为滴度为 107-108TCID5。的 PV-1病毒悬液与 3%的牛血清蛋白有机干 扰物质对倍稀释备用,测试发现中和剂溶液和中和产物溶液不影响脊椎灰质炎病 毒的活性。
灭活脊椎灰质炎病毒的功效试验, 分别测试了 0. 5分钟、 1. 0分钟、 1. 5分 钟, 杀灭对数值全部大于 4
0. 5分钟 1. 0分钟 1. 5分钟
样品 1 2. 6 3. 1 3. 8
样品 2 2. 3 3. 2 3. 7
样品 3 2. 5 2. 9 3. 7
样品 4 2. 5 3. 1 3. 9
样品 5 3. 2 3. 8 4. 1
样品 6 3. 1 3. 6 3. 9
样品 7 4. 1 5. 5 6. 4
样品 8 4. 2 5. 4 6. 3
样品 9 3. 9 4. 8 6. 1
样品 10 4. 1 4. 9 5. 9 发明产品的安全性
安全性试验分别使用了
1、 小鼠急性经口毒性试验: 经口 LD5。>5000mg/kg体重, 毒性分级属实际 无毒。 瑞士种昆明远交系小鼠 20只, 体重 18-22克, 雌性各半, 动物房温度 25 ° C, 相对湿度为 50%。 剂量分组 6000mg/kg体重, 染毒前动物禁食过夜, 自由饮 水, 染毒液配制为 300毫克 /毫升, 染毒体积为 0. 2ml/10g体重一次灌胃。 观测 期为 14天, 动物未见任何异常, 更没有动物死亡。
2、 多次完整皮肤剌激试验: 总积分平均值为 0, 皮肤剌激指数〈0. 5, 剌 激强度属无剌激性。 日本大耳白家兔 3只, 均为雌性, 体重 2-2. 5kg, 动物房温 度 25° C, 相对湿度为 50%。 试验前 24h, 将动物背部两侧的毛剪掉, 去毛范围左 右各 3cmX3cm。 次日将受测原液 0. 5ml直接滴于面积为 2. 5cmX2. 5cm大小的 2层 纱布上, 并敷贴在一侧的皮肤表面, 然后用一层无剌激油纸覆盖, 再用无剌激胶 布固定。 另一侧为空白对照, 作用 4h, 然后用温水洗去残留物, 每天一次, 连 续 14天, 结果显示, 3只家兔给药侧皮肤均未见红斑和水肿。
3、 小鼠骨髓嗜多染红细胞微核试验: 对小鼠骨髓嗜多染红细胞无致微核 作用。 瑞士种昆明远交系小鼠 50只, 雌性各半, 体重 25-30g, 动物房温度 25° C, 相对湿度为 50%。 环磷酰胺(CP)为阳性对照。 受试动物设 3个剂量组, 5000、 2000、 和 500mg/kg体重, 阳性对照组环磷酰胺 40mg/kg, 另设一个阴性对照组,
每组 10只小鼠, 雌性各半。 药物配制为 5、 2、 0. 5g, 分别加蒸馏水至 20毫升, 环磷酰胺 20mg加生理盐水至 5ml。 动物染毒用经口灌胃 30h染毒法, 两次染毒 间隔 24h, 第二次染毒后 6h取材。 染毒体积为 0. 2ml/10g体重, 环磷酰胺为腹 腔注射, 0, lml/10g体重。 颈椎脱臼法杀鼠, 取一侧股骨, 剥除肌肉, 擦净血污, 切断股骨两端暴露骨髓腔。 注射器吸取 0. lml小牛血清, 冲洗骨髓腔, 用冲洗液 常规涂片, 自然晾干。 将已干涂片, 甲醇中固定 5-10min, Giemsa 染液染色 10-15min, 缓冲液冲洗, 晾干。 选细胞分布均匀、 完整、 着色适当的区域, 在油 镜下计数含微核的嗜多染红细胞(PCE), 每只动物计数 1000 个 PCE, 观测 PCE/NCE (成熟红细胞)的比例, 微核细胞率全部小于千分之 0. 6 (和阴性对照相 同), 阳性对照微核细胞率为千分之 41。
4、 亚急毒性试验: 最大未观测到有害作用剂量(NOAEL) lOOOmg/kg体重。 Wi star贰级大鼠 40只, 6-8周龄, 雌性各半, 体重 180-220g, 动物房温度 25° C, 相对湿度为 50%。 受试组为 3组, 剂量为 1000、 500、 250mg/kg体重, 和对 照组。 受试液 25、 12. 5、 6. 25g, 分别加蒸馏水至 250ml。 大鼠 lml/100g体重灌 胃染毒, 对照着给等量的蒸馏水, 每天染毒一次, 连续 28天。 每周称重一次, 根据重量调整给药量。末次染毒后 24h检测各项指标, 然后杀鼠做组织病理学检 査。 血液分析项目为红细胞总数、 白细胞总数、 红细胞比积、 血红蛋白含量、 血 小板总数; 血生化检测包括 AST、 ALT, B環、 TP、 ALB、 GLU、 CH0; 脏器重量测 肝、 肾重量, 并计算脏器重量系数; 病理学检测包括所有内脏。
本发明揭示的新产品, 可以迅速杀死病菌、 真菌, 并迅速灭活病毒, 同时, 产品对皮肤没有剌激性, 对机体没有任何毒性。
以上所述仅为本发明的较佳实施例而已, 并非用以限定本发明的实质技术内 容范围, 本发明的实质技术内容是广义地定义于申请的权利要求范围中, 任何他 人完成的技术实体或方法, 若是与申请的权利要求范围所定义的完全相同, 也或 是一种等效的变更, 均将被视为涵盖于该权利要求范围之中。
在本发明提及的所有文献都在本申请中引用作为参考, 就如同每一篇文献被 单独引用作为参考那样。 此外应理解, 在阅读了本发明的上述内容之后, 本领域 技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权 利要求书所限定的范围。
Claims
1.一种免洗迅速灭毒制剂组合物, 其特征在于, 所述组合物包括以下重量组分: 50〜99重量份 C2〜C4挥发性醇;
0. 01〜5重量份用于提高组合物体系离子强度的离子;
其余组分为水。
2. 如权利要求 1所述的组合物, 其特征在于, 所述提高组合物体系离子强度的 离子为一价离子、 二价离子、 三价离子或其组合, 优选二价离子或三价离子, 更优 选三价离子。
3. 如权利要求 2所述的组合物, 其特征在于, 所述离子是一价阳离子、 一价阴 离子、 二价阳离子、 二价阴离子、 三价阳离子、 三价阴离子或其组合。
4. 如权利要求 3所述的组合物, 其特征在于,
所述一价阳离子为钠离子、 钾离子、 铵离子或其组合;
所述二价阳离子为碱土金属离子、 或过渡金属离子;
所述三价阳离子为钪离子、 钇离子、 或镧离子;
所述一价阴离子为一价卤素阴离子、 一价含氧负离子、 或一价有机离子; 所述二价阴离子为硫酸根离子、 碳酸根离子、 或双酸根离子;
所述三价阴离子为磷酸根离子。
5. 如权利要求 3所述的组合物, 其特征在于, 所述离子为磷酸根离子。
6. 如权利要求 1所述的组合物, 其特征在于, 所述组合物体系的离子强度为 16-500mM之间。
7. 如权利要求 1所述的组合物, 其特征在于, 所述挥发性醇选自乙醇、 丙醇、 丁醇、 或其组合。
8. 如权利要求 1所述的组合物, 其特征在于, 所述的离子的存在形式为所述离 子在水中、 或醇类溶剂中的可溶性盐。
9. 一种如权利要求 1所述的组合物制得的制剂。
10. 一种如权利要求 9所述的制剂的制备方法, 其特征在于, 包括如下步骤:
(a)提供以下 50〜99重量份 C2〜C4挥发性醇;
(b)将 0. 01〜5重量份用于提高组合物体系离子强度的离子与所述挥发性醇混 合; 所述离子的存在形式为所述离子在水中、 或醇类溶剂中的可溶性盐。
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JP2007217394A (ja) * | 2006-02-16 | 2007-08-30 | I-Nage:Kk | 医薬組成物 |
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US6136771A (en) * | 1999-06-23 | 2000-10-24 | The Dial Corporation | Compositions containing a high percent saturation concentration of antibacterial agent |
JP2007217394A (ja) * | 2006-02-16 | 2007-08-30 | I-Nage:Kk | 医薬組成物 |
CN101579203A (zh) * | 2008-05-14 | 2009-11-18 | 王传 | 一种新型点钞水湿巾及其生产方法 |
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