CN106139172A - A kind of bactericidal medical ultrasonic couplant and preparation method thereof - Google Patents

A kind of bactericidal medical ultrasonic couplant and preparation method thereof Download PDF

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Publication number
CN106139172A
CN106139172A CN201610680816.2A CN201610680816A CN106139172A CN 106139172 A CN106139172 A CN 106139172A CN 201610680816 A CN201610680816 A CN 201610680816A CN 106139172 A CN106139172 A CN 106139172A
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China
Prior art keywords
locust bean
bean gum
medical ultrasonic
preparation
bactericidal
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Withdrawn
Application number
CN201610680816.2A
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Chinese (zh)
Inventor
王传秀
史维倩
郑宇然
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Qingdao Yuntian Biotechnology Co Ltd
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Qingdao Yuntian Biotechnology Co Ltd
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Priority to CN201610680816.2A priority Critical patent/CN106139172A/en
Publication of CN106139172A publication Critical patent/CN106139172A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/22Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/736Glucomannans or galactomannans, e.g. locust bean gum, guar gum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/74Synthetic polymeric materials
    • A61K31/765Polymers containing oxygen

Abstract

The invention discloses a kind of bactericidal medical ultrasonic couplant and preparation method thereof, wherein, this bactericidal medical ultrasonic couplant consists of the following composition: modified locust bean gum, Polyethylene Glycol, glycerol, L aspartic acid and the water of surplus;Described modified locust bean gum is that locust bean gum reacts obtain with 2 chloroethyl trimethyl silanes, diethylamine in the presence of sodium iodide.The bactericidal medical ultrasonic couplant that the present invention provides has strong bactericidal action and can promote that the contact surface of wound heals, and has huge market using value.

Description

A kind of bactericidal medical ultrasonic couplant and preparation method thereof
Technical field
The present invention relates to a kind of bactericidal medical ultrasonic couplant and preparation method thereof.
Background technology
Commonly use ultrasonic coupling agent in medical ultrasonic diagnosis and treatment as medium, be used for strengthening ultrasonic probe and human body skin it Between coupling and isolation ultrasonic probe and examined area skin between air, make in sound wave conductive process reduce decay, Result is checked accurately to obtain.Therefore, the definition of ultrasonic medical image and resolving power, except relevant to equipment, also with super The quality of acoustic couplant is closely related.In ultrasonic medical, owing to ultrasonic probe is carried out with person under inspection's body skin or tract mucosa Contact, during continuous ultrasound diagnosis and treatment, ultrasonic probe frequently contacts different patient, there is the potential danger of medical cross infection.
Public affairs in " hospital's ultrasonic probe and commercially available couplant product " (China's Disinfection magazine, 2012,29 (4), 209-291) Having opened Shen et al. and inspected multiple commercially available couplant product by random samples, total number of bacteria exceeding standard rate is 40%, and the detection of one of which couplant is green Pus bacillus.The a lot of formula of existing couplant realizes the effect of ultrasonic coupling agent sterilization, sterilization only by addition antibacterial Agent is the best with other components do match, and not only bactericidal effect is undesirable, and the even membership that adds of antibacterial affects whole ultrasonic coupling agent Performance, such as CN101658680B discloses a kind of ultrasonic coupling agent, this ultrasonic coupling agent uses iodine, potassium iodide, iodic acid Potassium, hydrogen peroxide cause the allergy even skin burn of skin as sterilization component, the membership that adds of strong oxidizing property antibacterial, and Affect the stability of ultrasonic coupling agent formulation.In ultrasonic coupling agent disclosed in it such as CN103007305B, CN105327369A All use " triclosan " (triclosan) to add to ultrasonic coupling agent as antibacterial, and triclosan has Liver and kidney poison Property, carcinogenecity, restriction has been made in all uses to triclosan of the U.S., European Union and China.Ultrasonic probe as precise part, one As processing method ultrasonic probe is had damage, hospital is commonly used not to disinfect.The medical of existing a large amount of use surpasses Acoustic couplant does not typically the most possess disinfecting and sterilizing functions, causes ultrasonic probe not reach sterilisation level.Especially, when ultrasonic spy When head contacts with the skin having wound or tract mucosa, disinfecting of ultrasonic probe itself becomes particularly important, as What develops a kind of skin being suitable for having wound or tract mucosa and the ultrasonic coupling that the contact surface of wound can be promoted to heal Agent is particularly important.
In view of the excellent treatment effect of medical ultrasound equipment and its be widely applied, this area needs exploitation one tool badly There are strong bactericidal action and the ultrasonic coupling agent that the contact surface of wound can be promoted to heal.
Summary of the invention
It is an object of the invention to overcome existing ultrasonic coupling agent bactericidal property the best and be not suitable for there is wound The defect of contact surface, it is provided that a kind of have strong bactericidal action and the antibacterial type ultrasonic coupling that the contact surface of wound can be promoted to heal Agent and preparation method thereof.
To achieve these goals, the present invention provides a kind of bactericidal medical ultrasonic couplant, wherein, this bactericidal medical Ultrasonic coupling agent consists of the following composition: modified locust bean gum, Polyethylene Glycol, glycerol, ASPARTIC ACID and surplus Water;Described modified locust bean gum is that locust bean gum reacts with 2-chloroethyl trimethyl silane, diethylamine in the presence of sodium iodide Arrive.
In the present invention, this bactericidal medical ultrasonic couplant weight percentage composition can be:
Modified locust bean gum 3~10%
Polyethylene Glycol 3~8%
Glycerol 3~12%
ASPARTIC ACID 0.3~0.7%
And the water of surplus.
In the present invention, the preparation method of described modified locust bean gum includes: under nitrogen protection, by locust bean gum, iodine Change sodium, chloromethyl trimethyl silane, diethylamine join in reaction bulb, and 50~55 DEG C are reacted 10~15 hours, are cooled to room temperature, Filtering, filtrate concentrates, and normal hexane is recrystallized to give modified locust bean gum.In the case of in the present invention, it is preferred to, at modified locust bean gum In the preparation method of glue, locust bean gum, sodium iodide, chloromethyl trimethyl silane, the consumption weight ratio of diethylamine be 1:0.3~ 0.4:0.4~0.5:0.2~0.3.It is further preferred that in the preparation method of modified locust bean gum, locust bean gum, iodate Sodium, chloromethyl trimethyl silane, the consumption weight ratio of diethylamine are 1:0.3:0.4:0.2.
The present invention also provides for the preparation method of a kind of above-mentioned bactericidal medical ultrasonic couplant, and this preparation method includes:
1) Polyethylene Glycol, glycerol and water are mixed, be heated to 75~85 DEG C, be incubated 10 minutes;
2) ASPARTIC ACID, modified locust bean gum are sequentially added into step 1) heat mixed solution in, filtered while hot;
3) by step 2) filtrate that is filtrated to get is cooled to room temperature, supersound process 5~10min, and obtain bactericidal medical and surpass Acoustic couplant.
It was found by the inventors of the present invention that by locust bean gum in the presence of sodium iodide with 2-chloroethyl trimethyl silane, diethyl Amine carries out reaction can obtain modified locust bean gum, and modified locust bean gum is organosilicon and quaternary ammonium salt-modified product, with poly-second Glycol, glycerol, ASPARTIC ACID and water cooperation are made colorless transparent gel shape medical ultrasonic coupling agent and can be sterilized by force And promote the contact surface healing of wound.The antibacterial type ultrasonic coupling agent of the present invention can comply fully with YY 0299-2008 mark Accurate.
Compared with prior art, advantages of the present invention is: the antibacterial type ultrasonic coupling agent of the present invention need not additionally add Antibacterial, it is to avoid be individually added into the antibacterial impact on ultrasonic coupling agent stability etc.;The ultrasonic coupling agent of the present invention is to work Do not stimulate with position;The antibacterial type ultrasonic coupling agent range of application of the present invention is wider, may be used for having the skin of wound, have wound Mucosa etc., and simultaneously have promote wound healing effect;The ultrasonic coupling agent attenuation quotient of the present invention is little, probe and Form good infiltration, not mummification after coating between skin, it is possible to keep viscosity, pop one's head in along the detection smooth and easy sliding in position, and in Water solublity, easy cleaning.The antibacterial type ultrasonic coupling agent preparation technology of the present invention is simple, is particularly suitable for large-scale production.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is expanded on further.But these embodiments be only limitted to illustrate the present invention and not It it is the further restriction to protection scope of the present invention.In the present invention, all statistics are all carried out in SPSS19.0 software, its In, measurement data independent samples t-test, ranked data rank test.
Preparation example 1
Under nitrogen protection, 100g locust bean gum, 30g sodium iodide, 40g chloromethyl trimethyl silane, 25g diethylamine are added Entering in reaction bulb, 55 DEG C are reacted 10 hours, are cooled to room temperature, filter, and filtrate concentrates, and it is modified that normal hexane is recrystallized to give 98g Locust bean gum G1.
Preparation example 2
Under nitrogen protection, 100g locust bean gum, 10g sodium iodide, 40g chloromethyl trimethyl silane, 40g diethylamine are added Entering in reaction bulb, 70 DEG C are reacted 10 hours, are cooled to room temperature, filter, and filtrate concentrates, and it is modified that normal hexane is recrystallized to give 82g Locust bean gum G2.
Embodiment 1
A kind of bactericidal medical ultrasonic couplant, its preparation method is as follows:
1) 5g Polyethylene Glycol, 12g glycerol and 75.7g water are mixed, be heated to 80 DEG C, be incubated 10 minutes;
2) 0.3g ASPARTIC ACID, 7g modification locust bean gum (preparation example 1G1) are sequentially added into step 1) heat mixed Close in solution, filtered while hot;
3) by step 2) filtrate that is filtrated to get is cooled to room temperature, supersound process 10min, and obtain colorless transparent gel shape and kill Bacterial type medical ultrasonic coupling agent S1.
Embodiment 2
A kind of bactericidal medical ultrasonic couplant, its preparation method is as follows:
1) 8g Polyethylene Glycol, 3g glycerol and 85.3g water are mixed, be heated to 80 DEG C, be incubated 10 minutes;
2) 0.7g ASPARTIC ACID, 3g modification locust bean gum (preparation example 1G1) are sequentially added into step 1) heat mixed Close in solution, filtered while hot;
3) by step 2) filtrate that is filtrated to get is cooled to room temperature, supersound process 10min, and obtain colorless transparent gel shape and kill Bacterial type medical ultrasonic coupling agent S2.
Embodiment 3
A kind of bactericidal medical ultrasonic couplant, its preparation method is as follows:
1) 3g Polyethylene Glycol, 7g glycerol and 79.5g water are mixed, be heated to 75 DEG C, be incubated 10 minutes;
2) 0.5g ASPARTIC ACID, 10g modification locust bean gum (preparation example 1G1) are sequentially added into step 1) heat In mixed solution, filtered while hot;
3) by step 2) filtrate that is filtrated to get is cooled to room temperature, supersound process 5min, and obtain colorless transparent gel shape and kill Bacterial type medical ultrasonic coupling agent S3.
Embodiment 4
Bactericidal medical ultrasonic couplant as described in Example 1, except that, use the G2 of identical weight to substitute G1, obtains colorless transparent gel shape medical ultrasonic coupling agent S4.
Comparative example 1
Ultrasonic coupling agent as described in Example 1, except that, in preparation method, use the Robinia pseudoacacia L. of identical weight Locust beam gum substitutes modified locust bean gum, obtains ultrasonic coupling agent DS1.
Comparative example 2
Ultrasonic coupling agent as described in Example 1, except that, in preparation method, do not use ASPARTIC ACID, To ultrasonic coupling agent DS2.
Test case
One, ultrasonic coupling agent performance test
Ultrasonic coupling agent S1-S4 and DS1, DS2 have been carried out performance test, and concrete outcome is as shown in table 1.
Table 1
The velocity of sound is measured under 35 DEG C and 4.0MHz according to the method for GB/T15261, and sample length is 6cm;
Viscosity is rotary viscous according to " Pharmacopoeia of People's Republic of China two " version annex VI G " viscosimetry " in 2010 Degree meter method is measured at 25 DEG C;
PH value is measured according to " Pharmacopoeia of People's Republic of China two " 2010 version annex VI H " pH value algoscopy ";
Acoustic attenuation measures by double sample methods under 35 DEG C and 4.0MHz according to the method in GB/T15261, and with sound in water Decay is modified, and the difference of two sample lengths is more than 5cm.
Two, ultrasonic coupling agent irritation test
1, Skin Irritation Test
Test method: (2.0 ± 0.2Kg, by Beijing Vital River Experimental Animals Technology Co., Ltd. to take 48 healthy rabbits There is provided), male and female half and half, at random rabbit is divided into 14 groups of (often group male and female half and half, 7 groups of intact skin groups, 7 groups of wounds according to sex Skin group), by hair cutting (the unilateral shaving area about 40cm of rabbit spinal column both sides2), and uniform application 10% sodium sulfide is de- Except residue hair stubble, observe the depilation equal not damaged of skin, carry out modeling.To trauma skin group, with sterilizing No. 16 syringe needles in unhairing Mark about 2cm on skin #4, not hinder corium, to have slight oozing of blood to be advisable.Test uses own control, and left side does not process and does On the right side of rabbit in blank, 6 groups of intact skin groups and 6 groups of trauma skin groups unhairing region smear respectively S1, S2, S3, S4, DS1, DS2, use distilled water to clean after 24 hours, after cleaning, position skin is smeared in 1h, 24h, 48h, 72h perusal Skin, and record the situation that erythema and edema occur.
Skin wound repair standards of grading such as table 2.
Table 2
Skin irritation intensity evaluation according to score value is: 0~0.5 is nonirritant;0.5~2.0 is minimal irritation;2.0 ~6.0 be moderate zest;6.0~8.0 is strong and stimulating.
The concrete result of the test of skin irritation is as shown in table 3.
Table 3
The ultrasonic coupling agent (the particularly ultrasonic coupling agent in embodiment 1-3) of the present invention is the most right as can be seen from the above table Intact skin is still to trauma skin all nonirritants.It addition, according to above-mentioned erythema and edema situation, find that the present invention's is ultrasonic Couplant to intact skin and trauma skin all without sensitization.
Three, ultrasonic coupling agent bactericidal effect test
S1-S4 and DS1, DS2 being applied to ultrasonic probe, detects after 2 minutes, testing result is as shown in table 4.
Table 4
Bactericidal property is carried out according to regulation C.3 in GB/T15979-2002 appendix C.
As can be seen from the above table, the ultrasonic coupling agent of the present invention all has superpower sterilization energy for various common bacterias Power, thus ensured that ultrasonic probe will not produce nosocomial infection to patient during frequently using.
Four, the coagulant blood of ultrasonic coupling agent and rush skin healing test
1, each to S1-S4 and DS1, DS2 1g is added separately in test tube, takes rabbit arteria auricularis blood, rapid injecting tube, Every test tube 1ml, shakes up after adding, timing immediately.1 blank test tube is additionally set, is not added with any ultrasonic coupling agent.Often group is flat Four tests of row, statistical result such as table 5.
Table 5
Start clotting time/s Complete setting time/the s of blood
S1 362±27 471±29
S2 371±32 474±40
S3 365±36 467±51
S4 384±42 511±43
DS1 402±33 547±40
DS2 422±27 564±43
Blank 451±37 577±45
2,28 healthy rabbits (1.8 ± 0.5Kg is provided) are taken by Beijing Vital River Experimental Animals Technology Co., Ltd., Male and female half and half, are divided into 7 groups (often group male and female half and half) at random, by ether inhalation anesthesia, slough by portion's hair according to sex by rabbit, raw With 2% iodine tincture, 75% ethanol successively sterilization after reason saline cleaning, drying, excise the circular full thickness skin of a diameter of 0.5cm.Its In 6 groups of respectively external application S1-S4 and DS1, DS2, remain one group and do not process, as blank group.Conventional raising, observes wound Mouth healing state, and record, concrete outcome is as shown in table 6.
Table 6
Smear Rabbit quantity/only Average scab forming time/h Average decrustation time/h
S1 4 23 156
S2 4 26 161
S3 4 25 162
S4 4 32 190
DS1 4 40 210
DS2 4 45 224
Blank 4 50 265
Scab forming time is the time occurring fiber protein yarn bottom test tube.
From table 5, table 6 it can be seen that the present invention bactericidal medical ultrasonic couplant also have promotion blood coagulation and The effect of wound healing.
To sum up, the invention provides a kind of bactericidal medical ultrasonic couplant, this bactericidal medical ultrasonic couplant has Strong bactericidal action and the ultrasonic coupling agent that the contact surface of wound can be promoted to heal.

Claims (6)

1. a bactericidal medical ultrasonic couplant, it is characterised in that this bactericidal medical ultrasonic couplant is by following component group Become: modified locust bean gum, Polyethylene Glycol, glycerol, ASPARTIC ACID and the water of surplus;Described modified locust bean gum is thorn Locust bean gum reacts obtain with 2-chloroethyl trimethyl silane, diethylamine in the presence of sodium iodide.
Bactericidal medical ultrasonic couplant the most according to claim 1, it is characterised in that this bactericidal medical ultrasonic couples Agent weight percentage composition is:
Modified locust bean gum 3~10%
Polyethylene Glycol 3~8%
Glycerol 3~12%
ASPARTIC ACID 0.3~0.7%
And the water of surplus.
Bactericidal medical ultrasonic couplant the most according to claim 1 and 2, it is characterised in that described modified locust bean gum Preparation method include: under nitrogen protection, locust bean gum, sodium iodide, chloromethyl trimethyl silane, diethylamine are joined instead Answering in bottle, in THF, 50~55 DEG C are reacted 10~15 hours, are cooled to room temperature, filter, and filtrate concentrates, and normal hexane is recrystallized to give Modified locust bean gum.
4. according to the bactericidal medical ultrasonic couplant described in claim 1-3, it is characterised in that in the system of modified locust bean gum In Preparation Method, locust bean gum, sodium iodide, chloromethyl trimethyl silane, the consumption weight ratio of diethylamine are 1:0.3~0.4:0.4 ~0.5:0.2~0.3.
Bactericidal medical ultrasonic couplant the most according to claim 4, it is characterised in that in the preparation of modified locust bean gum In method, locust bean gum, sodium iodide, chloromethyl trimethyl silane, the consumption weight ratio of diethylamine are 1:0.3:0.4:0.25.
6. the preparation method of bactericidal medical ultrasonic couplant described in any one in claim 1-5, it is characterised in that should Preparation method includes:
1) Polyethylene Glycol, glycerol and water are mixed, be heated to 75~85 DEG C, be incubated 10 minutes;
2) ASPARTIC ACID, modified locust bean gum are sequentially added into step 1) heat mixed solution in, filtered while hot;
3) by step 2) filtrate that is filtrated to get is cooled to room temperature, supersound process 5~10min, obtains bactericidal medical ultrasonic coupling Mixture.
CN201610680816.2A 2016-08-16 2016-08-16 A kind of bactericidal medical ultrasonic couplant and preparation method thereof Withdrawn CN106139172A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106729925A (en) * 2017-03-29 2017-05-31 邱发龙 The preparation method and gel spray of a kind of gel spray repaired for wound

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102512696A (en) * 2011-12-31 2012-06-27 戴新春 Medical ultrasonic couplant and preparation method thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102512696A (en) * 2011-12-31 2012-06-27 戴新春 Medical ultrasonic couplant and preparation method thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106729925A (en) * 2017-03-29 2017-05-31 邱发龙 The preparation method and gel spray of a kind of gel spray repaired for wound

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Application publication date: 20161123