CN1092937A - A kind of antiviral coating that can be used for the latex viral barrier items such barrier item - Google Patents

Abstract

A kind of antiviral emulsion or lotion that is applied to mammal skin, be used for as under the skin protection utensils such as surgical glove or sheath, contain very a spot of a kind of alkylbenzene methyl quaternary ammonium halide disinfectant that skin can tolerate, acceptable nonionic of the skin that a kind of amount is very little or cationic surfactant, a kind of thickener such as ultrasonic coupling agent, a kind of softening agent such as G ﹠ W.

Description

A kind of antiviral coating that can be used for the latex viral barrier items such barrier item

The present invention relates to antiviral composition, relate in particular to the antiviral composition that is exclusively used in mammal skin appearance topical application.

One of main path of propagating between health of virus causes because of the contact of solid table and body fluid mix, as viruses such as liver viroids, herpes virus, HID all whereby approach propagate.Especially the working healthily personnel have the danger that suffers this type of virus disseminating, and as these type of personnel such as rescue personnel, nurse, doctor, operation theater workers, they must participate in and often continuously be engaged in Body contact with the virus infections person.So far, the mode of the most normal recommended anti-this type of virus infections is that protection skin screen is defended the doctrine always, and just the emgloves that is used by the healthcare worker and those are exposed to the latex prophylactic that the viral personnel that spread through sex intercourse use.

Yet still there is to a certain degree worry in people to the usefulness of this class skin protection utensil.If this appliances in use requires to reach the sensitivity of being allowed, just must be as thin as a wafer.This latex utensil is thin more, and the danger that they are subjected to mechanical damage is just big more, and they are also big more to danger that the virion that is comprised has infiltration in various degree.In addition, no matter how carefully make and preserve this class barrier item, still usually exist the risk that too much hole can appear in the utensil situation.

Purpose of the present invention is the effect that will strengthen this type of latex skin barrier item, to prevent the propagation of harmful virus between human body.

The invention provides one and unite the antivirus gel prescription of use with viral barrier item and emgloves and sheath.This prescription and a kind of and be with water base skin can accept carrier mass to be mixed with semi-solid gel, but it contains the strong disinfectant or the antibacterial material of the skin receiving amount of minute quantity, and this prescription is applied on the mammalian skin under viral barrier item such as emgloves and the sheath.This disinfectant or antibacterial material even can accept to kill harmful virus of contact under the required necessary low concentration of composition of the present invention at skin.Thereby the user is provided a kind of duplicate protection, with resist must contact the virus infections of infected individuals, this duplicate protection is viral barrier item and is coated in antibacterial agent or disinfectant gel below it.

Therefore, according to the present invention, from an aspect, a kind of latex barrier item that is applicable to certain position of health that is provided has suppressed virus and has propagated to the there, above-mentioned latex utensil has an outer surface and an inner surface that contacts with body part, above-mentioned inner surface has one deck semisolid, antivirus gel or missible oil, it contains 0.005～0.1%(weight of having an appointment) alkylbenzene methyl quaternary ammonium halide disinfectant, about 0.01～0.1%(weight) nonionic or cationic surfactant, and a kind of lubricated nontoxic abnormal former water-soluble thickener and water, wherein amounts of thickener should make that composition has semisolid, the missible oil denseness.

Being used for alkylbenzene methyl quaternary ammonium halide disinfectant of the present invention is a kind of compound known, in the past a variety of sterilisation purposes of being sold and being used for non-skin contact application in this compounds.Thereby the purpose of selling this compounds is to be used to make wash the local detergent with sterilizing of floor, wall, operating table surface or the like, avoids strong warning that it is contacted with skin as far as possible but often have prompting.In the time of as class brute force skin antiseptic, they also have strong toxicity and skin irritation.By the present invention, when this compounds was present in the prescription with the acceptable low concentration of skin, they can be killed as hepatitis, herpe simplex 1 type and 2 types and HIV virus.In fact, be independent of and be not difficult to be killed when outside body fluid or secretion exist when running into these viruses.May effectively have been killed hardly and after they have infected body of mammals and have begun to duplicate in somatic cell, just become.If be captured and handle in the process that virus can be propagated, just be subjected to killing of general disinfectant easily, as the compound that uses in the present invention between human body.

For avoiding occurring skin irritatin, strong disinfectant is preferably in the present composition and uses, and measures the weight ratio into 0.005-0.5%(); Optimum amount is the 0.005-0.001%(weight ratio).The concrete representation compound of the strong disinfectant of this class of Shi Yonging comprises alkyl-dimethyl benzyl ammonium chloride and alkyl dimethyl ethylbenzylammonium chloride in the present invention, and wherein the moieties chain length is C ₁₂-C ₁₈, comprise its mixture and myristylbenzalkonium chloride.The appropriate mixture of these compounds can have been bought from the market, and its commodity are called MAQUAT MQ2525M-50%, the registration of Si Zhou Chicago, Illinois Mason (Mason) chemical company; Another commodity are called BTC 2125M Illinois Si Zhou, North Field, Stepan register of company.

Also comprised a kind of a spot of nonionic or cationic surfactant in the present composition, it plays a kind of disinfectant lubricant, and it has increased disinfectant sending out in the dermal application zone.Prescription consumption and disinfectant that surfactant suits are approaching, i.e. the 0.01-0.1%(weight ratio), be preferably the 0.01-0.05%(weight ratio).The useful concrete representative of surfactant of this class comprise the polyoxyethylene fundamental mode as octoxynol series, belong to Polyethylene Glycol P-isooctylphenyl, octoxynol-9(Triton X-100); And nonoxynol series, they are the polyoxyethylene nonyl phenylates with various number ethylene oxide units, as nonoxydol 9 and nonoxydol 10.The advantage of this class material is that it uses in the present invention and kills sperm cell characteristics in addition.The polyoxyethylene groups non-ionic surface active agent that another type is suitable for is a polyoxy ethanol, as the compound of commercially available commodity " Siponic " by name.But " non-ionic surface active agent " Dekker that the selection reference standard reference book W.J.Schick of other surfactant writes, New York, 1967.Most important selection criteria be on selected consumption can with skin and selected strong disinfectant can be miscible.

Other component in the present composition is a kind of non-toxicity time abnormal former water-soluble thickener and water, and its proportioning should be suitable for providing a kind of gel semi-solid products that is similar to the denseness of wiping hand missible oil that has.Many these class thickeners have commercially available, are generally used in the preparation industry of cosmetics and medicine.They are known to those skilled in the art.Various cellulose derivativess are suitable for this purposes, for example methylcellulose and various sodium carboxymethylcellulose, and as carbomer 910,934,934p, 940,941 and 1342; And carbopels 940,941 and 930(Goodyear provide).Preferably also can provide the to a certain degree compound of lubrication for final composition.Preferential especially is ultrasonic coupling agent, a kind of usually on diasonograph as the gel combination that contact with skin, this suitable 1-80%(weight that comprises), preferred 20-80%(weight), the composition of 30-40%(weight most preferably).Consumption can be selected according to desired denseness of final products and the concrete thickener of selecting (thickening power that some of them are stronger than having of other).

Various other components also can add in the composition of the present invention to improve proterties, make that people are glad to use.Thereby wherein can contain one or more softening agents such as glycerine, lanolin, aloe black false hellebore, paraffin oil, glycerine monoester, myrj compound, tween, DEG compound, with dodecyl sodium sulfate etc. or two or more mixture wherein, with the lubricity of improving composition and general oiliness.Can add various pastils and colouring agent if desired; The all necessary and skin-compatible of the combination of any use has the inertia to mobile component, nature, and its usage amount can not cause the instability of integral formulation emulsion denseness.

Can use the cosmetics of standard or medicine gel preparation steps and equipment to be prepared by prescription of the present invention.The adding of component, mixing temperature etc. are not had special key request, if can obtain a kind of uniformly, have an end-product of quite stable.

According to the concrete most preferably prescription of the present invention following formation (by weight) is arranged:

Water 53.74

Ultrasonic coupling agent (aquasonic gel) 42.50

Glycerine 2.27

Aloe black false hellebore oil 1.19

Triton X-100 0.10（octoxynol-9）

MQ2525-50% 0.05

Aromatic (Vanilla plant extracts) 0.15

The present invention is further described and illustrates in following concrete, non-limiting example.

Embodiment 1

According to the present invention, the emulsion formulations of a kind of semisolid, emulsion form thickness constitutes (percentage by weight) by following ingredients:

EDTA tetrasodium salt 0.05

octoxynol-9（TritonX-100） 0.02

BTC-2125 0.05

Glycerine 0.05

Methylcellulose (4000 cps) 1.0

Siponic c-20 5.0

Water 93.83

Preparation is at room temperature carried out, and said components is mixed in a container simply, tests its antiviral efficacy to human herpes 1 type and 2 type viruses then in vitro.

The bleb of Mi Nisi suddenly 1 type that obtains and the concrete clinical separation strain of 2 types virus are:

1 type separated strain 103,104,105,117.

2 type separated strains 109,106,142.

Viral suspension behind low-speed centrifugal, clarify and-70 ℃ frozen, its appeal is titrated and represent with TCID 50/0.1ml.

Virus with volume adds in the test formulations with the given concentration of result in the following form.Thereby emulsion is 10% adding virus back Cmax.

The mixed liquor that moves into virus was cultivated 10 minutes down at 22 ℃, soon with 10 times of dilutions of solvent of cooling off, use 4 solencyte cultures to determine residual infection power to every pipe dilution factor then, the result expresses with TCID 50/0.1ml, uses the solvent of no test formulations to organize in contrast.

After the cultivation, test formulations concentration is 10,5,2.5,1 in all test formulations/virus mixture, and 0.5,0.05% o'clock, test formulations residue virus activity was reduced to the level that can not detect.Solvent-laden control group activity is equivalent to 3.0 and 4.0log ¹⁰TCID 50/0.1ml.With concentration be 105,2.5,1,0.5, after the contact of 0.05% test formulations, the reduction amount of titration of virus surpasses 2log ¹⁰TCID ₃₀

For confirming above-mentioned experiment, test formulations/viral mixture was cultivated 10 minutes down at 37 ℃, was obtained the result of same inactivation by two types of exanthema virus.

Embodiment 2-Study on Virulence

The identical component that emulsion is described by above-mentioned example 1 is prepared with same relative scale.

The arm of 10 mouse is shaved hair expose epidermis, and be coated with emulsion in the exposed region part of each mouse, and observed 48 hours, the result is as follows:

The result

Mouse number of applications virulence

1 1 -

2 1 -

3 1 -

4 1 -

5 1 -

6 4 ^*-

7 4 -

8 4 -

9 4 -

(connecting table)

10 4 -

There is sign in-indication no visible virulence in 48 hours.

* emulsion served as to amount at interval to be coated with 4 times with 4 hours.

Embodiment 3

In metamorphosis test and failure test, according to above-mentioned this effect detailed, that prepreerence emulsion formulations is tested its anti-viruses of human hepatitis B that gives.

Viruses of human hepatitis B (HBD) liquid forms (Gilbralter biology laboratory by 5.0% calf serum (40ml) and 760 μ l HBD mixed preparing, Inc, HBV storehouse 11GBL reference number 018-272A-153) 2ml emulsion formulations and 0.2ml HBV prescription liquid are injected in 25 * 150mm glass tube the violent vortex of mixture 1 minute.Add 18ml and contain the trypticase soya broth cessation reaction of 2% serum, fully vortex and put and use ice bath.The virus control group is added to the same manner preparation of 2.0ml phosphate buffered saline(PBS) (PBS) by absorption 0.2ml HBV.Reactant mixture concentrates after with suitable sucrose gradient ultracentrifugation, and supernatant discards gently, and the precipitation agglomerate suspends again with 0.5ml PBS, and similar agglomerate is merged.The HBV particle is 60～65%.(sucrose) is with (late-zonal) ultracentrifugation purifying and fractionated under the linear gradient through late.The Dane particle fragment of refractive index between 1.396 and 1.404 is saved and concentrates standby.

Positive staining is used for the virion number that quantitatively destroyed by test formulations, and operating procedure is to add 2% potassium permanganate and inhale and go, and adds deionized water and inhales and go, and adds 1.5% uranium acetate, and inhales and go., count under 50,000 multiplication factors from 20 foursquare 10 visuals field of selecting at random with the Karen Phillips transmission electron microscope observing.Do not detect virion.Relatively control group confirms destroyed in 1 minute above 40,000 virion.

Negative staining is used for detecting the virion that changes on the form.The method in this step is to use the 5% uranium acetate aqueous solution of pH3.5, and suction is gone.In 30 or the more visual field of Karen Phillips transmission electron microscope from 6 squares of selecting at random, observe and thoroughly count four covert APO, APO ₁, APO ₂And AP ₃In each is covert.At AP ₂And AP ₃Go up mutually, the virion that is observed is all impaired on form, and is the height metamorphosis, and these viruses have not had appeal.On the contrary, contrast is marked on AP ₀Or AP ₁Can be observed obvious int virion on form in a large number mutually, and have contagiosity.

The mechanism of action of the present composition may be breaking of virosomal membrane.

Embodiment 4

Concrete according to the present invention, most preferred prescription carries out the inactivation of the MIV in vitro test of emulsion.

People T-chronic myeloid leukemia 1 type virus permanent cell line (MT-2) is stored in (Dulbecco's improvement Eagle's medium on the growth medium, contain 15% heat inactivation hyclone, the 2mm glutamine, the streptomycin of the penicillin of every ml 100iu and every ml 100 μ g).

HIV-1(III B) the prototype experiment strain is to obtain from H9 infection cell culture supernatant, is concentrated to 1000 times by tape transport in sucrose.The Strain that filters is by whole branch and be stored in-85 ℃ until application.Strain is determined with a kind of end last titration of MT-2 cell on one 96 hole microtitre slab construction eventually.Strain contains TCID 50 virus titers of 5.50log10 TCID 50/ml, adopts the Reed-Muench method to calculate.

For carrying out Study of cytotoxicity, the MT-2 cell just is exposed to various dilution compounds in the initial growth phase, and after 4 days, cell survival rate is estimated by the Tryptan-Glu exclusive method, and compared with no medicine.

Strain is melted the back and is diluted to obtain the necessary required virus quantity of inactivation method test with phosphate buffered saline(PBS).Untreated virus is as the TCID of this test ₅₀Contrast was exposed to HIV-this compound after 1 minute, handled and untreated virus, and contrast is with the continuous 10 times of dilutions of PBS liquid, and every part of dilution is used to infect the MT-2 cell with the method for past description.Expressing viral is monitored by the existence of plasomidum structure.The plasomidum that HIV induces is formed on to cultivate and uses a kind of plasomidum formation detection method to assess after 6 days.

When be exposed to (23-27 ℃) under room temperature untreated control group after 1 minute relatively the time, make the HIV appeal reduce by The compounds of this invention greater than 2.5log10TCID 50/ml.

Embodiment 5

By compare the most preferably emulsion effect of prescription that assessment the present invention is concrete with commercially available surgery emgloves.

By above-mentioned prescription, patient's both hands are coated with double emulsion, and every hand consumption approximately is 2 1/2 CC'S, and both hands are put on surgical glove more then.Under a kind of situation, the emulsion gloves are containing residual starch based powdered lubricant under the form usually.Another situation, gloves do not contain crocus.Gloves were stayed the user 16 hours on hand.

Remove gloves, centrifugal, the liquid/semi-solid content (remaining emulsion, user's sweat, crocus precipitation etc.) in the gloves is got rid of in the fingerstall.Extract these liquid residue after the merging, by the serial dilution technology of anti-HIV prototype experiment strain, carry out external HIV inactivation experiment, the virus titer of this anti-HIV prototype experiment strain uses MT-2 cell and 10 times of serial dilutions as described in the example 4.

The emgloves residue and the emgloves residue that contains crocus that do not contain crocus all show to make the log virus titer reduce greater than 3.0.As the emulsion effect of carrying out the emgloves test.And then proof is still kept it under at least 16 hours the situation and is made the virally inactivated characteristic of HIV mixing with emgloves by composition of the present invention.

Claims (14)

1, is applicable to and is placed on a health part to suppress the latex barrier item of virus to the propagation of this place, above-mentioned latex barrier item have an outer surface and with the inner surface of Body contact, should one deck semisolid be arranged interior table surface, antivirus gel or missible oil wherein contain the alkylaryl quaternary ammonium halide disinfectant of the 0.005-0.1% that has an appointment (weight);

A kind of nonionic or cationic surfactant, content are 0.01-0.1% (weight);

A kind of nonionic time abnormal former and mixable thickener of water, its content is 1-80% (weight).

2,, mean a kind of latex surgical glove or a kind of latex prophylactic according to the latex barrier item of claim 1.

3, according to the latex barrier item of claim 2, wherein exist the disinfectant that accounts for the about 0.005-0.05% of weight.

4,, wherein exist the disinfectant of 0.005-0.01% amount by weight percentage according to the latex barrier item of claim 3.

5, according to the latex barrier item in the claim 3, wherein used disinfectant is selected from zephiran, and wherein alkyl is C ₁₂-C ₁₈Alkyl; And the alkyl dimethyl ethylbenzylammonium chloride, wherein alkyl is C ₁₂-C ₁₈Alkyl; And their mixture.

6, according to the latex protective device of claim 4, wherein the content of surfactant is 0.01-0.05%(weight).

7, according to the latex barrier item of claim 6, wherein surfactant is a kind of non-ionic surface active agent of polyethylene glycol oxide fundamental mode.

8, according to the latex barrier item of claim 7, wherein surfactant is oxtorynol-9.

9, according to the latex barrier item of claim 3, wherein thickener is a ultrasonic coupling agent.

10, according to the latex barrier item of claim 9, wherein the content of ultrasonic coupling agent is 30-40%(weight).

11, according to the latex barrier item of claim 3, wherein antivirus gel or emulsion contain softening agent.

12, according to the latex barrier item of claim 11, wherein softening agent is a glycerine.

13, a kind of semi-solid antivirus gel or emulsion compositions that is applied to mammiferous local skin under the viral barrier item, said composition contains a kind of alkyl benzyl quaternary ammonium halide disinfectant, and application quantity is the 0.005-0.1% percentage by weight;

A kind of nonionic or cationic surfactant, content are with restatement 0.01-0.1%;

A kind of nonionic time abnormal former and mixable thickener of water, accounting for weight is 1-80%;

And water.

14, composition according to claim 13, wherein disinfectant is selected from zephiran, and wherein alkyl is C ₁₂-C ₁₈Alkyl;

Alkyl dimethyl Ethylbenzyl chlorination thing, wherein alkyl is C ₁₂-C ₁₈Alkyl;

With and composition thereof.