CN109381479A - A kind of surgical operation anti-sticking flush fluid - Google Patents
A kind of surgical operation anti-sticking flush fluid Download PDFInfo
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- CN109381479A CN109381479A CN201710672681.XA CN201710672681A CN109381479A CN 109381479 A CN109381479 A CN 109381479A CN 201710672681 A CN201710672681 A CN 201710672681A CN 109381479 A CN109381479 A CN 109381479A
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- 239000012530 fluid Substances 0.000 title claims abstract description 29
- 239000002253 acid Substances 0.000 claims abstract description 39
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims abstract description 37
- 238000004945 emulsification Methods 0.000 claims abstract description 33
- 239000002502 liposome Substances 0.000 claims abstract description 33
- 238000002360 preparation method Methods 0.000 claims abstract description 32
- 229920002643 polyglutamic acid Polymers 0.000 claims abstract description 28
- 229920001661 Chitosan Polymers 0.000 claims abstract description 27
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 27
- 238000003756 stirring Methods 0.000 claims abstract description 27
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 25
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 25
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000004473 Threonine Substances 0.000 claims abstract description 23
- 239000011259 mixed solution Substances 0.000 claims abstract description 23
- 229960002898 threonine Drugs 0.000 claims abstract description 23
- 239000008215 water for injection Substances 0.000 claims abstract description 23
- 230000001954 sterilising effect Effects 0.000 claims abstract description 16
- 230000010355 oscillation Effects 0.000 claims abstract description 14
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 15
- 229960004275 glycolic acid Drugs 0.000 claims description 12
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 11
- 239000004626 polylactic acid Substances 0.000 claims description 11
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 9
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 9
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- 239000005642 Oleic acid Substances 0.000 claims description 9
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 9
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 9
- 241000894006 Bacteria Species 0.000 claims description 5
- 150000002632 lipids Chemical class 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 claims 1
- 210000002706 plastid Anatomy 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 230000000052 comparative effect Effects 0.000 description 21
- 238000004659 sterilization and disinfection Methods 0.000 description 12
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 9
- 230000015556 catabolic process Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 208000031737 Tissue Adhesions Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 230000002980 postoperative effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 206010000050 Abdominal adhesions Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000011010 flushing procedure Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 2
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- 238000002474 experimental method Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical group CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 208000031650 Surgical Wound Infection Diseases 0.000 description 1
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
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- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
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- 229950003499 fibrin Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 208000008384 ileus Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic 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 or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/717—Celluloses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of surgical operation anti-sticking flush fluids, preparation method includes the following steps: (1) sodium carboxymethylcellulose being added in water for injection, then gamma-polyglutamic acid and L-threonine is added to dissolving in stirring, mixed solution is stirred to get, it is spare；(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphasic liposomes, is then added into mixed solution obtained by step (1)；(3) be added carboxymethyl chitosan, supersonic oscillations, sterilizing to get.Anti-sticking flush fluid preventing adhesiving effect of the invention is good, degradable, and has preferable bactericidal property.
Description
Technical field
The present invention relates to field of medical technology, more particularly to a kind of surgical operation anti-sticking flush fluid.
Background technique
Surgical site infections are very easy to that tissue adhesion occurs, and so-called adhesion refers to connective fiber band and adjacent tissue
Or organ is combined together and the anomaly sxtructure that is formed, this is the process that patient is subjected in agglutination after surgery.If
There is adhesion in the operation such as abdominal cavity or pelvic cavity bone, serious complication will be caused, such as: abdomen, pelvic cavity etc. can draw
Adhesive ileus is played, recurrent nerve injury is caused after thyroid operation and because pelvic tissue adhesion leads to atocia in turn
Disease etc..
Organize the initiation reason of adhesion very much, such as: the wound formed in surgical procedure, ischaemic cause inflammation, body
Inside there is foreign matter, at bleeding or the bacterium infection of exposure wound.
At present other than the barrier film of medical mechanical domain, the most common method for preventing postoperative tissue adhesion is to pass through drug
Mitigate inflammatory reaction and solution fibrin, develops diversified adherence preventing material in recent years, but for the material that prevents adhesion
For material, on the basis of preventing adhesion, fast degradation and internal residual should can be reduced to the greatest extent, and present product effect is simultaneously
It is undesirable.
Summary of the invention
Present invention aim to provide a kind of surgical operation anti-sticking flush fluid.
To achieve the above object, the present invention is achieved by the following scheme:
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine stirs to get mixed solution, spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (1)；
(3) be added carboxymethyl chitosan, supersonic oscillations, sterilizing to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid are more
The mass volume ratio of phase liposome, carboxymethyl chitosan and water for injection be 0.01~0.02g:0.06~0.08g:0.03~
0.05g:0.02~0.03g:2~3g:0.08~0.1g:100mL.
One of as a preferred technical scheme, in step (1), the weight average molecular weight of gamma-polyglutamic acid is 1000~
1200kDa。
One of as a preferred technical scheme, in step (1), after gamma-polyglutamic acid and L-threonine is added, stirring 5~8
Hour.
One of as a preferred technical scheme, in step (2), the weight average molecular weight of poly lactide-glycolide acid is
120~150kDa.
One of as a preferred technical scheme, in step (2), poly lactide-glycolide acid be by mass ratio 1:2~
3 polylactic acid and hydroxyacetic acid is polymerized.
One of as a preferred technical scheme, in step (2), the process conditions of ultrasonic emulsification are as follows: ultrasonic frequency is
80~100kHz, emulsification times are 5~8 hours.
One of as a preferred technical scheme, in step (3), the weight average molecular weight of carboxymethyl chitosan is 400~
450kDa。
One of as a preferred technical scheme, in step (3), the supersonic oscillations time is 12~24 hours.
One of as a preferred technical scheme, in step (3), 121 DEG C of moist heat sterilizations of the use that sterilizes.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
The beneficial effects of the present invention are:
1, load medicine matrix of the invention is made sodium carboxymethylcellulose is soluble in water, is had certain viscosity, is helped to rush
Drug adhesion is rinsing position after washing lotion is rinsed, and then plays the therapeutic effect to prevent adhesion, and facilitate the fast prompt drop of each ingredient
Solution.
2, gamma-polyglutamic acid has stronger adsorptivity and biological degradability, and after L-threonine is added, the two collaboration increases
Mobility between tissue prevents tissue adhesion.
3, using polyphase liposome multiphasic liposomes are made in poly lactide-glycolide acid by the present invention, to wound
The capillary of discharge surface plays the role of covering, reduces blood or tissue fluid exudation, and then play the role of preventing adhesion.
4, the present invention is finally also added into carboxymethyl chitosan, with excellent biological barrier performance and tissue compatible
Property, it is cooperateed with sodium carboxymethylcellulose and plays bacteriostasis property.
Specific embodiment
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Embodiment 1
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine, stirring obtains mixed solution in 5 hours, spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (1)；
(3) be added carboxymethyl chitosan, supersonic oscillations 12 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid are more
The mass volume ratio of phase liposome, carboxymethyl chitosan and water for injection is 0.01g:0.06g:0.03g:0.02g:2g:
0.08g:100mL.
Wherein, in step (2), poly lactide-glycolide acid is gathered by the polylactic acid and hydroxyacetic acid of mass ratio 1:2
It closes.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 80kHz, emulsification times are 5 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Embodiment 2
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine, stirring obtains mixed solution in 8 hours, spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (1)；
(3) be added carboxymethyl chitosan, supersonic oscillations 24 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid are more
The mass volume ratio of phase liposome, carboxymethyl chitosan and water for injection is 0.02g:0.08g:0.05g:0.03g:3g:0.1g:
100mL。
Wherein, in step (2), poly lactide-glycolide acid is gathered by the polylactic acid and hydroxyacetic acid of mass ratio 1:3
It closes.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 100kHz, emulsification times are 8 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Embodiment 3
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine, stirring obtains mixed solution in 5 hours, spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (1)；
(3) be added carboxymethyl chitosan, supersonic oscillations 24 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid are more
The mass volume ratio of phase liposome, carboxymethyl chitosan and water for injection is 0.01g:0.08g:0.03g:0.03g:2g:0.1g:
100mL。
Wherein, in step (2), poly lactide-glycolide acid is gathered by the polylactic acid and hydroxyacetic acid of mass ratio 1:2
It closes.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 100kHz, emulsification times are 5 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Embodiment 4
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine, stirring obtains mixed solution in 8 hours, spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (1)；
(3) be added carboxymethyl chitosan, supersonic oscillations 12 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid are more
The mass volume ratio of phase liposome, carboxymethyl chitosan and water for injection is 0.02g:0.06g:0.05g:0.02g:3g:
0.08g:100mL.
Wherein, in step (2), poly lactide-glycolide acid is gathered by the polylactic acid and hydroxyacetic acid of mass ratio 1:3
It closes.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 80kHz, emulsification times are 8 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Embodiment 5
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine, stirring obtains mixed solution in 6 hours, spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (1)；
(3) be added carboxymethyl chitosan, supersonic oscillations 18 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid are more
The mass volume ratio of phase liposome, carboxymethyl chitosan and water for injection is 0.015g:0.07g:0.04g:0.025g:2.5g:
0.09g:100mL.
Wherein, in step (2), poly lactide-glycolide acid is the polylactic acid and hydroxyacetic acid by mass ratio 1:2.5
It is polymerized.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 90kHz, emulsification times are 7 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Comparative example 1
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid is added to dissolving in stirring, stir
Obtain mixed solution within 6 hours, it is spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (1)；
(3) be added carboxymethyl chitosan, supersonic oscillations 18 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, poly lactide-glycolide acid, polyphase liposome,
The mass volume ratio of carboxymethyl chitosan and water for injection is 0.015g:0.07g:0.025g:2.5g:0.09g:100mL.
Wherein, in step (2), poly lactide-glycolide acid is the polylactic acid and hydroxyacetic acid by mass ratio 1:2.5
It is polymerized.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 90kHz, emulsification times are 7 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Comparative example 2
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine, stirring obtains mixed solution in 6 hours, spare；
(2) poly lactide-glycolide acid is added while stirring；
(3) be added carboxymethyl chitosan, supersonic oscillations 18 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, carboxymethyl
The mass volume ratio of chitosan and water for injection is 0.015g:0.07g:0.04g:0.025g:0.09g:100mL.
Wherein, in step (2), poly lactide-glycolide acid is the polylactic acid and hydroxyacetic acid by mass ratio 1:2.5
It is polymerized.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 90kHz, emulsification times are 7 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Comparative example 3
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine, stirring obtains mixed solution in 6 hours, spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (1)；
(3) supersonic oscillations 18 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid are more
The mass volume ratio of phase liposome and water for injection is 0.015g:0.07g:0.04g:0.025g:2.5g:100mL.
Wherein, in step (2), poly lactide-glycolide acid is the polylactic acid and hydroxyacetic acid by mass ratio 1:2.5
It is polymerized.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 90kHz, emulsification times are 7 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Comparative example 4
A kind of preparation method of surgical operation anti-sticking flush fluid, comprising the following steps:
(1) sodium carboxymethylcellulose is added in water for injection, then gamma-polyglutamic acid and L- is added to dissolving in stirring
Threonine stirs 6 hours；
(2) carboxymethyl chitosan is added, stirs to get mixed solution；
(3) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase
Liposome is then added into mixed solution obtained by step (2)；Supersonic oscillations 18 hours, 121 DEG C of moist heat sterilizations to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid are more
The mass volume ratio of phase liposome, carboxymethyl chitosan and water for injection is 0.015g:0.07g:0.04g:0.025g:2.5g:
0.09g:100mL.
Wherein, in step (2), poly lactide-glycolide acid is the polylactic acid and hydroxyacetic acid by mass ratio 1:2.5
It is polymerized.The process conditions of ultrasonic emulsification are as follows: ultrasonic frequency 90kHz, emulsification times are 7 hours.
A kind of surgical operation anti-sticking flush fluid, is prepared by the preparation method.
Test example
1, sterilization test:
One ring of slant culture of staphylococcus aureus, Pseudomonas aeruginosa is taken to be inoculated in broth bouillon respectively, 37 DEG C
After culture 24 hours, respectively takes 0.2mL to be inoculated in 8 plating mediums, take 3 institute of Examples 1 to 5 or comparative example of equivalent respectively
The flushing liquor of preparation is dripped respectively in 8 plating mediums；Sterilization rate is detected after acting on 1min, 2min, 3min respectively；Knot
Fruit such as table 1.
1. sterilizing rate comparative test of table
As shown in Table 1, the flushing liquor of Examples 1 to 5 has good bactericidal effect, and processing can be killed big after 1 minute
Part bacterium, it is rapid-action, it is possible to prevente effectively from bacterium infection；Comparative example 3 omits the carboxymethyl chitosan in step (3), kills
Bacterium effect is obviously deteriorated, this is because carboxymethyl chitosan is cooperateed with sodium cellulose glycolate plays bactericidal effect, omits carboxylic first
Bactericidal property is had a greatly reduced quality after base enclosure glycan.
2, external proteolysis assay
External proteolysis assay is carried out according to the method in patent CN200710014412.0, investigates Examples 1 to 5 and right
The external enzymolysis property of the antiblocking liquor of ratio 2 and comparative example 4, the results are shown in Table 2.
Table 2. digests 48 hours in vitro and 96 hours degradation rates compare
| 48 hours degradation rates (%) | 96 hours degradation rates (%) | |
| Embodiment 1 | 93 | 100 |
| Embodiment 2 | 93 | 100 |
| Embodiment 3 | 95 | 100 |
| Embodiment 4 | 94 | 100 |
| Embodiment 5 | 96 | 100 |
| Comparative example 2 | 42 | 79 |
| Comparative example 4 | 65 | 86 |
As shown in Table 2, the antiblocking liquor of Examples 1 to 5 can degrade rapidly, 48 hours degradable major parts, reduce
Residual in vivo, 96 hours can be degradable.Lipid is not made in poly lactide-glycolide acid in the step of comparative example 2 (2)
Body, comparative example 4 have overturned the feeding sequence of step (2) and step (3), and the external degradation rate that digests is substantially reduced, and may bring
Safety issue.
3, animal experiment
Experimental method investigation is prevented adhesion for the postoperative of male SD rat according to the animal surgery of patent CN105963801A
Coating gel therein is replaced with and rinses hand using the flushing liquor of Examples 1 to 5 or comparative example 1~4 respectively by intestinal adhesion situation
The art surface of a wound, every group of quantity using male SD rat are 10, and postoperative intestinal adhesion the results are shown in Table 3.
3. postoperative intestinal adhesion evaluation of result of table
| (divide) after 2 weeks | (divide) after 3 weeks | |
| Embodiment 1 | 2 | 0 |
| Embodiment 2 | 1 | 0 |
| Embodiment 3 | 1 | 0 |
| Embodiment 4 | 1 | 0 |
| Embodiment 5 | 1 | 0 |
| Comparative example 1 | 8 | 15 |
| Comparative example 2 | 12 | 20 |
| Comparative example 3 | 7 | 16 |
| Comparative example 4 | 10 | 18 |
As shown in Table 3, polylactic acid-in the step of comparative example 1 omits the L-threonine in step (1), comparative example 2 (2)
Liposome is not made in co-glycolic acid, and comparative example 3 omits the carboxymethyl chitosan in step (3), and comparative example 4 is reverse
The feeding sequence of step (2) and step (3), preventing adhesiving effect is obviously deteriorated, much worse than Examples 1 to 5.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.
In addition, it should be understood that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
It considers the specification as a whole, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
The other embodiments being understood that.
Claims (10)
1. a kind of preparation method of surgical operation anti-sticking flush fluid, which comprises the following steps:
(1) by sodium carboxymethylcellulose addition water for injection, then gamma-polyglutamic acid and L- Soviet Union ammonia is added to dissolving in stirring
Acid stirs to get mixed solution, spare；
(2) poly lactide-glycolide acid is added into polyphase liposome, ultrasonic emulsification handles to obtain multiphase lipid
Body is then added into mixed solution obtained by step (1)；
(3) be added carboxymethyl chitosan, supersonic oscillations, sterilizing to get；
Wherein, sodium carboxymethylcellulose, gamma-polyglutamic acid, L-threonine, poly lactide-glycolide acid, oleic acid multiphase rouge
The mass volume ratio of plastid, carboxymethyl chitosan and water for injection is 0.01~0.02g:0.06~0.08g:0.03~0.05g:
0.02~0.03g:2~3g:0.08~0.1g:100mL.
2. preparation method according to claim 1, which is characterized in that in step (1), the Weight-average molecular of gamma-polyglutamic acid
Amount is 1000~1200kDa.
3. preparation method according to claim 1, which is characterized in that in step (1), gamma-polyglutamic acid and L- Soviet Union is added
After propylhomoserin, stir 5~8 hours.
4. preparation method according to claim 1, which is characterized in that in step (2), poly lactide-glycolide acid
Weight average molecular weight be 120~150kDa.
5. preparation method according to claim 1, which is characterized in that in step (2), poly lactide-glycolide acid
It is to be polymerized by the polylactic acid and hydroxyacetic acid of mass ratio 1:2~3.
6. preparation method according to claim 1, which is characterized in that in step (2), the process conditions of ultrasonic emulsification
Are as follows: ultrasonic frequency is 80~100kHz, and emulsification times are 5~8 hours.
7. preparation method according to claim 1, which is characterized in that in step (3), the Weight-average molecular of carboxymethyl chitosan
Amount is 400~450kDa.
8. preparation method according to claim 1, which is characterized in that in step (3), the supersonic oscillations time is 12~24
Hour.
9. preparation method according to claim 1, which is characterized in that in step (3), 121 DEG C of the use that sterilizes are damp and hot to go out
Bacterium.
10. a kind of surgical operation anti-sticking flush fluid is prepared by preparation method according to any one of claims 1 to 9
It obtains.
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