CN101757615A - Ointment for clearing nose planted staphylococcus aureus and preparing method thereof - Google Patents

Ointment for clearing nose planted staphylococcus aureus and preparing method thereof Download PDF

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Publication number
CN101757615A
CN101757615A CN200810044014A CN200810044014A CN101757615A CN 101757615 A CN101757615 A CN 101757615A CN 200810044014 A CN200810044014 A CN 200810044014A CN 200810044014 A CN200810044014 A CN 200810044014A CN 101757615 A CN101757615 A CN 101757615A
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China
Prior art keywords
ointment
chitosan
staphylococcus aureus
lysozyme
nose
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CN200810044014A
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Chinese (zh)
Inventor
黄青山
崔福英
陆婉英
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SHANGHAI GAOKE BIO-ENGINEERING Co Ltd
SHANGHAI GAOKE UNION BIOTECHNOLOGY DEVELOPMENT Co Ltd
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SHANGHAI GAOKE BIO-ENGINEERING Co Ltd
SHANGHAI GAOKE UNION BIOTECHNOLOGY DEVELOPMENT Co Ltd
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Priority to CN200810044014A priority Critical patent/CN101757615A/en
Publication of CN101757615A publication Critical patent/CN101757615A/en
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Abstract

The invention belongs to the technical field of medicines, and particularly relates to a biological preparation for clearing nose planted staphylococcus aureus (particularly MRSA) and a preparing method thereof. The preparation is prepared from the following components in percentage by weight: 0.0002-0.002% of staphylococcus lysozyme, 10-50% of Vaseline, 10-50% of emulsifying agent, 1-10% of fatty acid monoglyceride, 0.1-2% of protein stabilizing agent, and the balance of water. The prepared ointment preparation can obviously kill the staphylococcus aureus implanted in the nose, effectively control the cross infection in hospital due to the nose planted staphylococcus aureus (MRSA).

Description

Be used to remove the ointment machin its preparation method of nose planted staphylococcus aureus
Technical field
The invention belongs to medical technical field, relate to a kind of biological preparation of removing nose planted staphylococcus aureus and preparation method thereof that is used to specifically.
Background technology
Infection of staphylococcus aureus is popular one of strain the most widely in hospital and the community.Along with the increase of methicillin-resistant staphylococcus aureus (MRSA), MRSA has accounted for more than the 40-90% of golden Portugal bacterium infection in China's nosocomial infection, becomes a big problem that influences human health.Data show, at present the whole world have nearly 5,300 ten thousand people carry fatal " superbacteria "-MRSA (Lancet, 2006,874-885), MRSA is then even more serious in the infection of hospital and sanatorium.Any object in the hospital environment can be the source of infection, patient, health carrier, family numbers of patients, corpsman,hospital's nostril or all carry this pathogenic bacterium on hand.In the U.S., MRSA has become the skin of cross infection initiation in the community and primary pathogenic bacterium [the Invasive Methicillin-Resistant Staphylococcus aureus Infections in theUnited States of soft tissue bacterial infection, JAMA, 2007,298 (15): 1763-1771].Because vestibule of nose is the main habitat of MRSA, so all can carry MRSA in the gas of patient and medical personnel's exhalation.And traditional chemical disinfectant such as liquid chlorine, chlorine dioxide, bleaching powder or bleaching essence, ozone etc. can only be used for general environment disinfecteds such as ground, render a service very limited; Skin antiseptic such as povidone iodine, hibitane can not be directly used in the propagation with the blocking-up pathogen of oral cavity and nasal cavity, can not be used for wound surface and Mucocutaneous disinfection, thereby can't stop the main route of transmission of this nosocomial infection.Scholars have confirmed that the MRSA of nasal cavity field planting can cause severe infections, and the field planting rate that reduces MRSA can significantly reduce the incidence rate of cross infection in hospital MRSA.An example is that the infection of staphylococcus aureus rate is reduced to 0.71% from 11.7% of matched group after utilizing mupirocin ointment can make gastrointestinal surgery.Studies show that recently preventative intranasal uses mupirocin can reduce interpatient staphylococcus aureus cross infection in the hospital greatly.At present, Mupirocin Ointment (ointment that contains 2% mupirocin) is a kind of widely used antibiotic prescription drugs, can remove staphylococcus aureus in the vestibule of nose.Yet along with its large-scale use, MRSA shows stronger drug resistance to mupirocin, other several drugses such as neosporin ointment newly developed, and Polysporin ointment and bacitracin etc. are also relatively poor to the effect of MRSA.Therefore need the especially medicine of MRSA of the new staphylococcus aureus that can eradicate the nasal cavity field planting of exploitation
Summary of the invention
One of technical issues that need to address of the present invention provide a kind of ointment that is used to remove the nose staphylococcus aureus, to overcome the defective that existing product exists.
Another technical problem that the present invention need solve provides a kind of preparation method of removing the ointment of nose planted staphylococcus aureus.
Inventive concept of the present invention is such:
Staphylococcus lysozyme (lysostaphin) is that first was in isolating antibiotic enzyme from staphylococcus haemolyticus (Staphylococcusstaphylolyticus) in 1964.It is a kind of zinciferous metalloproteases, the glycine peptide bond of single-minded cracking gram-positive bacteria cell wall.Because the cell wall of staphylococcus aureus contains the glycine peptide bond of higher proportion, staphylococcus lysozyme can effectively cracking active growth and the staphylococcus aureus of rest period, comprises methicillin-resistant staphylococcus aureus (MRSA), rapid kill bacteria.It goes back other staphylococcus of cleavable, is difficult for producing drug resistance, and body is had no side effect.In addition, the antibacterial activity of fatty acid also is realized.They are to gram positive bacteria such as staphylococcus aureus and gram negative bacteria such as gonococcus, helicobacter pylori, and chlamydia trachomatis, incrusting type virus etc. all has antibacterial activity.Fatty acid and single glyceride thereof extensively are present in the plant, and nontoxic, and FDA classifies fatty acid mono glycidol as safe material.In conjunction with the antibacterial activity of staphylococcus lysozyme and glycerine monofatty ester, prepare the ointment formulation of novel removing nose planted staphylococcus aureus, will be expected to become the medicine of a kind of new anti-nasal cavity staphylococcus aureus that replaces mupirocin.
Because nasal cavity is very fast to foreign bodies removal, liquid and pressed powder are detained the half-life therein only 15min, and ointment formulation quality uniform and smooth, viscosity suitable, can the long period be stranded in na-sal cavity surfaces and not have nasal ciliary toxicity.And the ointment formulation of selecting for use suitable substrate adding medicine to make is easy to coat nasal mucosa.
Glycerine monofatty ester is a fat-soluble medicine, and therefore with stable in properties, the oleaginous base vaseline of chafe does not prepare ointment as substrate.But staphylococcus lysozyme and lysozyme are the protease materials, its in oiliness ointment, the character instability.Therefore selecting for use does not have the hydrophilic protein matter of influence or macromolecular material to form water parcel protease to keep the three dimensional structure of protease as protein stabiliser to the dissolving staphylococcal bacteria enzymatic activity, can avoid the destruction of other material.
Technical scheme of the present invention is as follows:
A kind of ointment that is used to remove nose planted staphylococcus aureus in weight percent, comprises staphylococcus lysozyme 0.0002-0.002%, vaseline 10-50%, emulsifying agent 10-50%, glycerine monofatty ester 1-10%, protein stabiliser 0.01-2%, water surplus.
The emulsifying agent of being addressed is a caprylic/capric triglyceride.
The glycerine monofatty ester of being addressed is more than one in glycerol monolaurate, single caprylin or lauric acid-sad monoglyceride.
The protein stabiliser of being addressed is more than one of collagen protein, albumin, chitosan or chitosan derivatives, sodium alginate, sodium carboxymethyl cellulose or Polyethylene Glycol.
The chitosan derivatives of being addressed is more than one in chitosan hydrochlorate, chitosan lactate, chitosan quaternary ammonium salt, glutamate, carboxymethyl chitosan or the using carboxyl chitosan.
The collagen protein of being addressed is more than one of I, II or III collagen type.
The Polyethylene Glycol of being addressed is a molecular weight 400,1500, more than one of 2000 or 4000 Polyethylene Glycol.
The ointment of the treatment nose infection of staphylococcus aureus of being addressed also comprises the lysozyme of percentage by weight 0.05-1%.
The ointment of the treatment nose infection of staphylococcus aureus of being addressed also comprises the Cera Flava of percentage by weight 0-10%.
The ointment of the treatment nose infection of staphylococcus aureus of being addressed also comprises the liquid paraffin of percentage by weight 0-10%.
The ointment of the treatment nose infection of staphylococcus aureus of being addressed also comprises the sodium benzoate of percentage by weight 0-0.5%.
Preferred ingredients and weight percentage comprise staphylococcus lysozyme 0.0005-0.0015%, lysozyme 0.05-0.3%, vaseline 20-50%, caprylic/capric triglyceride 20-40%, glycerol monolaurate 2-5%, Cera Flava 3-10%, sodium benzoate 0.3%, collagen protein 0.5-1.5%, water surplus.
The method of the ointment of the removing nose planted staphylococcus aureus that preparation is addressed is characterized in that, comprises the steps:
(1) staphylococcus lysozyme is dissolved in the protein stabiliser aqueous solution;
(2), stir cooling with emulsifying agent, vaseline and glycerine monofatty ester water-bath fusion; In the aqueous solution that adding step (1) makes, stir, make ointment.
The ointment formulation that the present invention makes can make staphylococcus lysozyme and the collaborative antibacterial action that plays of glycerine monofatty ester, thereby improves the sterilizing rate to staphylococcus aureus, widens its antimicrobial spectrum.Staphylococcus lysozyme is arranged in the water hydrophilic material of ointment, avoids directly contacting with liposoluble constituent, improves its stability, also can reduce in the nasal cavity hydrolytic enzyme to the degraded of staphylococcus lysozyme.Glycerine monofatty ester not only has bactericidal activity, can also cooperate with the emulsifying agent caprylic/capric triglyceride and strengthen emulsifying effectiveness, make that the staphylococcus lysozyme-protein stabilized agent solution and the oleaginous base compatibility of water are good, have suitable viscosity and stability, the raising medicine is in the action time of nose.The ointment formulation that the present invention makes also can be used for removing the staphylococcus aureus of the skin and the mucosa at other positions.The preparation method that is used to remove nose planted staphylococcus aureus ointment of the present invention is simple, is fit to large-scale production, and employed material is easy to get, and is with low cost, and product is easy to use.
The specific embodiment
The preparation of embodiment 1 ointment 1
Get 35g caprylic/capric triglyceride (caprylic/capric=60: 40, letter International Trading Company Ltd available from prestige), the single caprylin of 3g, 50g white vaseline, heating and melting, stir, after treating that substrate is cold slightly, to wherein adding the chitosan content be dissolved with the 0.0015g staphylococcus lysozyme is that aqueous solution to the total formulation weight amount of 1mg/ml is 100g, stirs and promptly gets the nose ointment formulation.
Embodiment 2 sterilizing rates are measured
With the nose ointment that makes among the embodiment 1 with contain Mycoderma (bacteria containing amount 10 7Cfu/ml), after the contact of spending the night, will contain Mycoderma dilution after, in the impouring flat board, 37 ℃, measuring sterilizing rate behind the 48h is 100%.
The preparation of embodiment 3 ointments 2
Get 30g caprylic/capric triglyceride, 5g glycerol monolaurate, 48g white vaseline, 3g Cera Flava heating and melting, stir, after treating that substrate is cold slightly, to the collagen content of staphylococcus lysozyme that wherein adds 0.0005g and 0.0995g lysozyme is that aqueous solution to the total formulation weight amount of 60mg/ml is 100g, stirs and promptly gets nose ointment formulation 2.
The preparation of embodiment 4 ointments 3
Get 30g caprylic/capric triglyceride, 5g glycerol monolaurate, 48g white vaseline, 3g Cera Flava heating and melting, stir, after treating that substrate is cold slightly, to wherein adding the collagen content be dissolved with 0.0015g staphylococcus lysozyme and 0.2985g lysozyme is that aqueous solution to the total formulation weight amount of 60mg/ml is 100g, stirs and promptly gets nose ointment formulation 3.
Embodiment 5 bactericidal effect comparative experimentss
With the nose ointment 2 in embodiment 3 and 4 and nose ointment 3 respectively with contain Mycoderma (10 7Cfu/ml), contact 2h and 4h respectively after, will contain Mycoderma dilution after, in the impouring flat board, 37 ℃, measure sterilizing rate behind the 48h, as seen along with the increase of time of contact, sterilizing rate has the trend of increase for result such as table 1..
Table 1 nose ointment sterilizing rate result
Figure G2008100440148D0000041
Embodiment 6 acid-base value are measured
Sample thief adds the water jolting, and the aqueous solution of gained is met phenolphthalein or the equal invariant color of methyl orange indicator.
Embodiment 7 acute infection of staphylococcus aureus rhinitis model experiments
Adopt the staphylococcus aureus yeast to increase the venom nasal drip and prepare rat rhinitis model, staphylococcus aureus strain MRSAI face fresh preparation of time spent (1 * 109cfu/ml), get 10ml bacterium liquid and add the 1g dry yeast.Each is organized rat and gives the staphylococcus aureus yeast and increase toxicity liquid 120ul/d collunarium, collunarium 4d modeling continuously.Rat increases venom collunarium bacterial infection through the antibacterial yeast, can comparatively fast cause bacterial infection, and bacterial infection increases the weight of rat uneasiness, rhinorrhea behind third and fourth day collunarium.After the modeling of last collunarium, be applied to rat nose ointment 3 once a day, get nasal mucosa with bamboo let after the administration for three days on end and do the antibacterial cultivation, do not detect staphylococcus aureus.

Claims (11)

1. an ointment that is used to remove nose planted staphylococcus aureus is characterized in that, in weight percent, comprise staphylococcus lysozyme 0.0002-0.002%, vaseline 10-50%, emulsifying agent 10-50%, glycerine monofatty ester 1-10%, protein stabiliser 0.01-2%, water surplus.
2. ointment as claimed in claim 1 is characterized in that the emulsifying agent of being addressed is a caprylic/capric triglyceride.
3. ointment as claimed in claim 1 is characterized in that, the glycerine monofatty ester of being addressed is more than one in glycerol monolaurate, single caprylin or lauric acid-sad monoglyceride.
4. ointment as claimed in claim 1 is characterized in that the protein stabiliser of being addressed is more than one of collagen protein, albumin, chitosan or chitosan derivatives, sodium alginate, sodium carboxymethyl cellulose or Polyethylene Glycol.
5. ointment as claimed in claim 4 is characterized in that, described chitosan derivatives is more than one in chitosan hydrochlorate, chitosan lactate, chitosan quaternary ammonium salt, glutamate, carboxymethyl chitosan or the using carboxyl chitosan.
6. ointment as claimed in claim 4 is characterized in that, described collagen protein is more than one of I, II or III collagen type, and Polyethylene Glycol is a molecular weight 400,1500, more than one of 2000 or 4000 Polyethylene Glycol.
7. as the arbitrary described ointment of claim 1-4, it is characterized in that, by weight percentage, also comprise the lysozyme of 0.05-1%.
8. as the arbitrary described ointment of claim 1-4, it is characterized in that, also comprise in Cera Flava, liquid paraffin or the sodium benzoate more than one.
9. ointment as claimed in claim 8 is characterized in that the mellisic weight percentage of being addressed is 0-10%, and the weight percentage of liquid paraffin is 0-10%, and the weight percentage of sodium benzoate is 0-0.5%.
10. ointment as claimed in claim 1, it is characterized in that, preferred ingredients and weight percentage comprise staphylococcus lysozyme 0.0005-0.0015%, lysozyme 0.05-0.3%, vaseline 20-50%, caprylic/capric triglyceride 20-40%, glycerol monolaurate 2-5%, Cera Flava 3-10%, sodium benzoate 0.3%, collagen protein 0.5-1.5%, water surplus.
11. prepare the method for ointment as claimed in claim 1, it is characterized in that, comprise the steps:
(1) staphylococcus lysozyme is dissolved in the protein stabiliser aqueous solution;
(2), stir cooling with emulsifying agent, vaseline and glycerine monofatty ester water-bath fusion; In the aqueous solution that adding step (1) makes, stir, make ointment.
CN200810044014A 2008-11-26 2008-11-26 Ointment for clearing nose planted staphylococcus aureus and preparing method thereof Pending CN101757615A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108721610A (en) * 2018-06-25 2018-11-02 济南瑞丰生物工程有限公司 A kind of nasal cavity wetting agent of chitosan-containing and preparation method thereof
CN111567565A (en) * 2020-05-28 2020-08-25 江苏雪豹日化有限公司 Lysozyme complex

Citations (3)

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Publication number Priority date Publication date Assignee Title
CN1528150A (en) * 2003-10-16 2004-09-15 上海高科生物工程有限公司 Biological agent for foot disinfection
CN1878536A (en) * 2003-09-09 2006-12-13 3M创新有限公司 Antimicrobial compositions and methods
CN101288769A (en) * 2006-12-18 2008-10-22 上海高科生物工程有限公司 Bactericide for pet and preparation method thereof

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
CN1878536A (en) * 2003-09-09 2006-12-13 3M创新有限公司 Antimicrobial compositions and methods
CN1528150A (en) * 2003-10-16 2004-09-15 上海高科生物工程有限公司 Biological agent for foot disinfection
CN101288769A (en) * 2006-12-18 2008-10-22 上海高科生物工程有限公司 Bactericide for pet and preparation method thereof

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杨信怡等: "溶葡球菌酶的抗菌活性研究进展", 《中国新药杂志》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108721610A (en) * 2018-06-25 2018-11-02 济南瑞丰生物工程有限公司 A kind of nasal cavity wetting agent of chitosan-containing and preparation method thereof
CN111567565A (en) * 2020-05-28 2020-08-25 江苏雪豹日化有限公司 Lysozyme complex

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Application publication date: 20100630