CN101036667A - Gelatin for preventing conglutination in the surgical and the method for preparing the same - Google Patents
Gelatin for preventing conglutination in the surgical and the method for preparing the same Download PDFInfo
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- CN101036667A CN101036667A CN 200710014413 CN200710014413A CN101036667A CN 101036667 A CN101036667 A CN 101036667A CN 200710014413 CN200710014413 CN 200710014413 CN 200710014413 A CN200710014413 A CN 200710014413A CN 101036667 A CN101036667 A CN 101036667A
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Abstract
The invention discloses an anti-blocking gel used in surgery and a method for preparing the same. The anti-blocking gel comprises 1 weight% carboxymethyl chitosan having molecular weight of 300000-700000 dalton and 20-30 weight% water for injection, which dynamics viscosity is 800~3000 centipoise. The preparing method comprises: removing impurity protein pyrogen from the raw material; carboxymethyl-modification of chitin; purifying the carboxymethyl chitosan; preparing the anti-blocking gel and the preparation thereof. Accordingly, the anti-blocking gel has exellent biological barrier performance and histocompatibility, after applied on tissue wound surface, can prevent tissue tissue adhesion postoperation, which intermediary metabolite and final metabolite in human body are normal metabolites facilitating to be absorbed by the human body, without toxicity and acrimony. The anti-blocking gel has abundance material sources with low cost and simple process, thus has broad application prospects in clinical medicine art.
Description
(1) technical field
The present invention relates to a kind of surgical operation anti-adhesion gel and preparation method thereof, belong to surgery medical material technical field.
(2) background technology
The tissue adhesion is a great problem that clinical medicine faces always behind the surgical operation, the tissue adhesion of taking place behind surgical operations such as human abdomen, cardiovascular, spinal column, osteoarthrosis, tendon portion, gynecological's pelvic cavity not only brings great misery to the patient, and causes enormous economic loss.For solving the tissue adhesion problem, relevant scientific worker both domestic and external carries out unremitting effort always, and up to the present, the multiple adherence preventing material of having attempted can be divided into the three generations substantially.First generation material is the nondegradable mechanical barrier material of human body, as sheet metal, silk, sheet rubber, politef etc.; Second filial generation material is the barrier material that human body is difficult to absorb, as mineral oil, dextran, chitin etc.; Third generation material is the biomaterial that human body is easy to absorb, as hyaluronic acid, chitosan, polylactic acid etc.Wherein, first and second in generation material because of exist some can not degraded and absorbed, tissue is had stimulation, easily causes that defectives such as infection are eliminated by market gradually.Third generation material obtains the permission of FDA at present mostly, has obtained extensive use clinically, and still, these products more or less exist some purity and degradation speed to be difficult to weak points such as control.
(3) summary of the invention
The present invention is directed to the deficiency that prior art surgical postoperative adherence preventing material exists, a kind of surgical operation anti-adhesion gel and preparation method thereof is provided.
The present invention also provides a kind of surgical operation anti-adhesion gel preparation.
Technical scheme of the present invention is as follows:
1, surgical operation anti-adhesion gel
A kind of surgical operation anti-adhesion gel is refining carboxymethyl chitosan 1 weight portion of 30-70 ten thousand dalton and water for injection 20-30 weight portion by molecular weight, anti-adhesion gel dynamic viscosity 800-3000 centipoise; Described carboxymethyl chitosan molecular weight is 30-70 ten thousand dalton, and molecular structure unit is:
Wherein: R
1For hydrogen (H) or carboxymethyl (CH
2COOH), R
1Its content is 50%～80% mol ratio during for carboxymethyl,
R
2Be hydrogen (H), acetyl group (COCH
3) or carboxymethyl (CH
2COOH), R
2Its content during for carboxymethyl＞10% mol ratio, R
1, R
2Have at least one to be carboxymethyl, R
3For hydrogen (H) or carboxymethyl (CH
2COOH).
Above-mentioned refining carboxymethyl chitosan is that the chitin warp is obtained carboxymethyl chitosan except that foreign protein, carboxymethyl-modification, carboxymethyl chitosan is made through apirogen water dissolving, filtration, dehydrated alcohol flocculation final vacuum drying again.
2, the preparation of surgical operation anti-adhesion gel
The preparation method of a kind of surgical operation anti-adhesion gel of the present invention, step is as follows, is weight portion:
(1) removes foreign protein pyrogen in the chitin raw material
Take by weighing molecular weight greater than 1 part of 700,000 daltonian chitin, the sodium hydrate aqueous solution that adds 3～6 times of its weight, sodium hydrate aqueous solution concentration are 20%～40% (w/v), stir 30-60min down at 50 ℃～80 ℃, with apirogen water chitin is washed the neutrality to pH, dry standby.
Described chitin is the commercially available prod.
(2) carboxymethyl-modification of chitin
Taking by weighing 1 part of the chitin handled through step (1), is that the sodium hydrate aqueous solution of 45%～50% (w/v) soaks 0.5～5h with 3～4 parts of concentration at room temperature, and 100～120rpm rotating speed is fully stirring down.Add 15～25 parts of isopropyl alcohols, continuation is 5～10 parts of the dirty aqueous isopropanols that adds monoxone of stirring condition, this solution monoxone concentration is 60%～80% (w/w), under 0 ℃～10 ℃ conditions, reacted 23～25 hours, centrifugal filtration reaction mash obtains solid then, with 75%～80% washing with alcohol solid 2～6 times, is neutralized to pH neutrality with dilute hydrochloric acid in the washing process, get carboxymethyl chitosan, dry standby.
(3) refining carboxymethyl chitosan
Under aseptic condition, above-mentioned carboxymethyl chitosan is fully dissolved with the aseptic apirogen water of 80～100 times of volumes, the elimination insoluble matter, with molecular cut off is the carboxymethyl chitosan sugar aqueous solution is filtered and the dialyses operations of 70-30 ten thousand daltonian films, with the progressively dilute filtration degerming of carboxymethyl chitosan sugar aqueous solution in the bag filter, being diluted to final strength of fluid is 0.1%w/v then.With the dehydrated alcohol flocculation carboxymethyl chitosan of 2～4 times of volumes of this solution,, get purified carboxymethyl chitosan then with the carboxymethyl chitosan vacuum drying after the flocculation.
Preferably, 0.22 μ m filter membrane is adopted in above-mentioned dilute filtration degerming.
Preferably, above-mentioned flocculation dehydrated alcohol is through 0.22 μ m membrane filtration.
Through the refining carboxymethyl chitosan that above step makes, aseptic, apyrogeneity, molecular weight 30～700,000 dalton.
(4) preparation anti-adhesion gel
Under aseptic condition, take by weighing the refining carboxymethyl chitosan of step (3), prepare the anti-adhesion gel of anti-adhesion gel dynamic viscosity 800～3000 centipoises according to following ratio with pyrogen-free utensil:
1 part of refining carboxymethyl chitosan
Water for injection 20-30 part.
3, the preparation of surgical operation anti-adhesion gel preparation
Under aseptic condition, above-mentioned anti-adhesion gel is stirred, fully swelling is canned then in the Dispoable medical syringe, gets the anti-adhesion gel preparation, preserves under 0 ℃ of-10 ℃ of condition.
Above-mentioned anti-adhesion gel is canned in the Dispoable medical syringe, 1 milliliter～20 milliliters of loading amount specifications.
The technical characterstic of anti-adhesion gel of the present invention is to have adopted refining carboxymethyl chitosan, select molecular weight greater than 700,000 daltonian chitin raw materials, the molecular weight that guarantees finished product is greater than 300,000 dalton, by using alkali concn, alkali charge, R is guaranteed in the preferred control of process conditions such as soak time, monoxone consumption, reaction temperature, response time
1, R
2, R
3Molar content in described scope.By dialysis operation to the carboxymethyl chitosan sugar aqueous solution, molecular weight is removed less than 300,000 daltonian small molecular weight impurities, make refining aseptic, the apyrogeneity of carboxymethyl chitosan, molecular weight 30～700,000 dalton.
Excellent results of the present invention is as follows:
Anti-adhesion gel of the present invention has adopted refining carboxymethyl chitosan, selects suitable molecular weight and carboxymethyl content, has good biological barrier performance and histocompatibility, is applied to and organizes wound surface, prevents the postoperative tissue adhesion.Anti-adhesion gel of the present invention intermediate supersession in human body is the normal metabolite of human body with final metabolite, is easy to human body and absorbs avirulence and zest.In addition, these anti-adhesion gel raw material sources are abundant, and cheap, preparation technology is simple, has broad application prospects at clinical medicine domain.
Anti-adhesion gel of the present invention can overcome the defective of existing adherence preventing material effectively, has the product purity height, water solublity and good biocompatibility, lower-price characteristic, and anti-adhesion gel preparation of the present invention is easy to use, and specification is optional.The preparation method of anti-adhesion gel of the present invention, easy and simple to handle, be easy to suitability for industrialized production, have favorable industrial application prospect.
(4) specific embodiment
Embodiment 1
A kind of surgical operation anti-adhesion gel is refining modified carboxy methyl chitosan 1 weight portion of 35-40 ten thousand dalton and water for injection 30 weight portions by molecular weight, anti-adhesion gel dynamic viscosity 900 centipoises; The preparation method step is as follows:
(1) removes pyrogen such as foreign protein in the chitin raw material
Take by weighing molecular weight about 750,000 daltonian commercially available chitin 2kg, add the 6kg sodium hydrate aqueous solution, sodium hydrate aqueous solution concentration is 20% (w/v), stirs 6 hours under 70oC, with apirogen water chitin is washed the neutrality to pH, dries standby.
(2) carboxymethyl-modification of chitin
Taking by weighing the chitin 1kg that step (1) is handled, is that the sodium hydrate aqueous solution of 45% (w/v) soaked 3 hours with 3kg concentration at room temperature, and 100～120rpm rotating speed is fully stirring down.Add the 18kg isopropyl alcohol, continuation is at the dirty aqueous isopropanol 5kg that adds monoxone of stirring condition, this solution concentration is 60% (w/w), reaction is 23 hours under 5 ℃ of conditions, centrifugal filtration reaction mash obtains solid then, with 75% washing with alcohol solid 3 times, be neutralized to pH neutrality with dilute hydrochloric acid in the washing process, dry the carboxymethyl chitosan that obtains standby.Gained carboxymethyl chitosan molecular weight 35-40 ten thousand dalton.
(3) refining carboxymethyl chitosan
Above-mentioned modified carboxy methyl chitosan is fully dissolved with the apirogen water of 80 times of volumes, the elimination insoluble matter, with molecular cut off is after 450,000 daltonian films filter the carboxymethyl chitosan sugar aqueous solution, collect filtrate, the reuse molecular cut off is 300,000 daltonian films to the operation of dialysing of this filtrate, then with the progressively dilute filtration degerming of carboxymethyl chitosan sugar aqueous solution in the bag filter (0.22 μ m film), then with the dehydrated alcohol of 3 times of volumes of this solution flocculation carboxymethyl chitosan, this dehydrated alcohol is used 0.22 μ m membrane filtration in advance, and the purified carboxymethyl chitosan vacuum drying in back that will flocculate is standby.
(4) preparation anti-adhesion gel
Under aseptic condition, take by weighing the purified carboxymethyl chitosan of step (3), prepare anti-adhesion gel with pyrogen-free utensil according to following ratio:
Refining carboxymethyl chitosan 0.5kg
Water for injection 15kg
Anti-adhesion gel dynamic viscosity 900 centipoises.
Above-mentioned anti-adhesion gel is stirred, and fully swelling is canned in the Dispoable medical syringe under aseptic condition, gets the anti-adhesion gel preparation, and the loading amount specification can be preserved under 0 ℃～10 ℃ conditions from 5 milliliters/to 15 milliliters/.
Embodiment 2
A kind of surgical operation anti-adhesion gel is refining modified carboxy methyl chitosan 1 weight portion of 60-65 ten thousand dalton and water for injection 20 weight portions by molecular weight, anti-adhesion gel dynamic viscosity 2800 centipoises; Its preparation methods steps is as follows:
(1) except that pyrogens such as foreign proteins in the raw material
Take by weighing molecular weight about 900,000 daltonian commercially available chitin 2kg, add the 10kg sodium hydrate aqueous solution, sodium hydrate aqueous solution concentration is 25% (w/v), stirs 5 hours down at 80 ℃, with apirogen water chitin is washed the neutrality to pH, dries standby.
(2) carboxymethyl-modification of chitin
Taking by weighing above-mentioned chitin 1kg, is that the sodium hydrate aqueous solution of 50% (w/v) soaked 5 hours with 4kg concentration at room temperature, and 100～120rpm rotating speed fully stirs down.Add the 25kg isopropyl alcohol, continuation is at the dirty aqueous isopropanol 10kg that adds monoxone of stirring condition, this solution concentration is 60% (w/w), reaction is 25 hours under 6 ℃ of-10 ℃ of conditions, centrifugal filtration reaction mash obtains solid then, with 80% washing with alcohol solid 6 times, be neutralized to pH neutrality with dilute hydrochloric acid in the washing process, dry the carboxymethyl chitosan that obtains standby.Gained carboxymethyl chitosan molecular weight is 60-65 ten thousand dalton.
(3) refining carboxymethyl chitosan
Above-mentioned carboxymethyl chitosan is fully dissolved with the apirogen water of 100 times of volumes, the elimination insoluble matter, with molecular cut off is after 650,000 daltonian films filter the carboxymethyl chitosan sugar aqueous solution, collect filtrate, the reuse molecular cut off is 600,000 daltonian films to the operation of dialysing of this filtrate, then with the progressively dilute filtration degerming of carboxymethyl chitosan sugar aqueous solution in the bag filter (0.22 μ m film), use dehydrated alcohol (this dehydrated alcohol is used 0.22 μ m membrane filtration in advance) the flocculation carboxymethyl chitosan of 4 times of volumes of this solution then, the purified carboxymethyl chitosan vacuum drying in back that will flocculate is standby.
(4) preparaton and fill
Under aseptic condition, take by weighing the refining carboxymethyl chitosan of step (3), prepare the anti-adhesion gel preparation with pyrogen-free utensil according to following ratio:
Refining carboxymethyl chitosan 0.5kg
Water for injection 10kg
Anti-adhesion gel dynamic viscosity 2800 centipoises
The anti-adhesion gel of aforementioned proportion stirs, and fully swelling is canned in the Dispoable medical syringe under aseptic condition, and the loading amount specification can be preserved standby under 0 ℃-10 condition from 2 milliliters/to 5 milliliters/.
Embodiment 3
Under aseptic condition, take by weighing the carboxymethyl chitosan of refining after drying among the embodiment 2, prepare the anti-adhesion gel preparation with pyrogen-free utensil according to following ratio:
Refining carboxymethyl chitosan 0.1kg
Water for injection 2.5kg
Anti-adhesion gel dynamic viscosity 1600 centipoises
Above-mentioned anti-adhesion gel fully stirs, and fully swelling is canned in the Dispoable medical syringe under aseptic condition, and 2 milliliters/of loading amount specifications are preserved under 0 ℃-10 condition, and are standby.
Comparative test example one:
Anti-adhesion gel for preparing in the foregoing description and commercially available hyaluronic acid are comparing aspect the external enzymolysis property, and the degradation rate comparative result is as shown in table 1.
Table 1: external enzymolysis 72 hours and 120 hours degradation rates are relatively
Above-mentioned external enzymolysis test concrete grammar is as follows:
1, purpose:
Observe the situation of adherence preventing material, study the biodegradation character of this series products at the external use bio-enzyme degradation.
2, material:
1 of electronic balance, lysozyme (SIGMA company) 1g, the phosphate buffer of PH7.4,1 of 100mL volumetric flask, 2 in 10mL suction pipe, 100mL beaker 2 each, each 20 of the triangular flasks of 300mL, 1 of constant temperature oscillator, 2 of vacuum desiccators.
3, method:
(1) preparation of lysozyme liquid: take by weighing lysozyme 500mg with electronic balance, put into the 100mL volumetric flask, be settled to 100mL with the phosphate buffer (PBS) of PH7.4, the preparation lysozyme soln, this lysozyme concentration is 5mg/mL.
(2) get high concentration (30mg/mL) sample and each 10mL of low concentration (15mg/mL) sample with suction pipe, add respectively in the different triangular flask (50mL), labelling is finished writing in 10 bottles of repetitions of every kind of sample.
(3) add lysozyme liquid 10mL, mixing with suction pipe in the bottle to respectively shaking.
(4) all are shaken bottle and be placed on the constant temperature shaking table temperature: 37 ℃, shaking speed: 60 rev/mins.
4, analyzing and testing:
(1) after cultivating 48 hours on the shaking table, get the bottle that shakes of two kinds of samples and handle for 2 bottles, earlier 50mL is shaken in the triangular flask that bottle liquid changes 300mL respectively over to, add dehydrated alcohol 80mL respectively, thoroughly shake up, left standstill 20 minutes.
(2) the liquid 6000rpm in each bottle is centrifugal, supernatant discarded is collected solid content.
(3) solid content is put into the beaker vacuum drying to constant weight, respectively with scales/electronic balance weighing and record.
(4) every 72 hours, the bottle that shakes of getting two kinds of samples respectively carried out above same operation for each 2 bottles after.
5, result treatment:
(1) sample degraded situation is represented with degradation rate:
Annotate: sample dry matter weight before gross weight before the reaction=reaction+lysozyme dry matter weight
(2) each institute gets two and shakes a bottle individual processing, and the meansigma methods of getting both then is as real degradation rate.
(3) the sample dry matter weight is meant before the reaction: outturn sample is precipitated with the dehydrated alcohol of its 4 times of volumes, and collecting precipitation carries out the weight of the material of gained behind the vacuum drying.
Comparative test example two:
Anti-adhesion gel for preparing in the foregoing description and commercially available hyaluronic acid are in the comparison (concrete experimental technique is asked for an interview adnexa 2) that experimentizes aspect the adhesion of prevention rat intestine, and adhesion degree comparative result is as shown in table 2.
Table 2: prevention rat intestine adhesion test comparative result
Above-mentioned rat intestine adhesion test method is as follows:
1, experiment material
1) animal: 72 of healthy rats, male, body weight 250～270g, random packet, 12 every group.
2) anti formulation samples at different levels; Normal saline solution is as blank, and positive control is selected hyaluronate sodium for use.
3) experiment equipment: dissect and sterilize standby with operating theater instruments two covers, dry gauze (60-90 fritter, 2～4 bulks), dissecting pan; Ethanol for disinfection or iodine tincture.Operation suture silk (No. 1)
4) medicine: pentobarbital sodium (2%, lumbar injection dosage 30mg/kg)
2, experimental technique
1) anesthesia: all animals adopts pentobarbital sodium intraperitoneal injection of anesthesia (30mg/kg).When the animal peace and quiet, breathe steady balance, blood pressure is normal, abdominal wall muscle is lax, corneal reflex is blunt, can carry out every experimental implementation when no anoxia shows.
2) dorsal position is fixed after the Animal Anesthesia, the cropping sterilization, take off median abdominal incision under the sterile working, be about 2-3cm, find out ileocecus after opening the abdominal cavity, get one section long ileum of 10cm apart from ileocecus 5cm place, with dry gauze repeatedly gently wiping tunica serosa intestini tenuis layer make impaired (the about 0.4cm * 10cm) of serous coat, there is the tip-like petechia on the surface, and gauze is dyed pale red.
3) the branch group to wound surface coated sample 2ml, and reference substance be 2ml, the coating scope is whole wound surface, then it is put back to the abdominal cavity, successively closes abdomen, sews up.
4) postoperative animal fasting 12h, sub-cage rearing, feedstuff are full nutrition rat pellet.
5) behind the 14d again anesthesia or put to death rat after, open the abdomen check, draw materials, judge the adhesion grade.
3, experimental result
1) observation item
(1) intra-abdominal adhesions diagnostic criteria
Divide the adhesion situation that grade standard is determined rat equally according to Zhong Jian.0 grade: do not have adhesion fully; The I level: the local slight adhesion in 1-2 place, with finger easily separately; II level: the adhesion of two places above I level sample is arranged; III level: adhesion is widely arranged, the part separation difficulty; The IV level: intestinal tube each other or closely adhesion between the peritoneum, mesentery, tangle agglomerating, separation difficulty.
(2) om observation: every group of wound site intestinal tube 0.5cm that gets 3 rats at random, specimens paraffin embedding slices, serous coat wound repair situation is observed in H-E dyeing.
Claims (6)
1. a surgical operation anti-adhesion gel is refining carboxymethyl chitosan 1 weight portion of 30～700,000 dalton and water for injection 20～30 weight portions by molecular weight, anti-adhesion gel dynamic viscosity 800～3000 centipoises; Described refining carboxymethyl chitosan molecular structure unit is:
Wherein: R
1For hydrogen (H) or carboxymethyl (CH
2COOH), R
1Its content is 50%～80% mol ratio during for carboxymethyl, R
2Be hydrogen (H), acetyl group (COCH
3) or carboxymethyl (CH
2COOH), R
2Its content during for carboxymethyl＞10% mol ratio, R
1, R
2Have at least one to be carboxymethyl, R
3For hydrogen (H) or carboxymethyl (CH
2COOH);
Above-mentioned refining carboxymethyl chitosan is that the chitin warp is got carboxymethyl chitosan except that foreign protein, carboxymethyl-modification, makes through apirogen water dissolving, filtration, dehydrated alcohol flocculation final vacuum drying again.
2. the preparation method of a surgical operation anti-adhesion gel, step is as follows, is weight portion:
(1) removes foreign protein pyrogen in the chitin raw material
Take by weighing molecular weight greater than 1 part of 700,000 daltonian chitin, the sodium hydrate aqueous solution that adds 3～4 times of its weight, sodium hydrate aqueous solution concentration are 20%～40%w/v, stir 30～60min down at 50 ℃～80 ℃, with apirogen water chitin is washed the neutrality to pH, dry;
(2) carboxymethyl-modification of chitin
Take by weighing 1 part of the chitin handled through step (1), at room temperature the sodium hydrate aqueous solution that is 45%～50%w/v with 3～4 parts of concentration soaks 0.5～5h, 100～120rpm rotating speed fully stirs down, add 15～25 parts of isopropyl alcohols, continuation is 5～10 parts of the dirty aqueous isopropanols that adds monoxone of stirring condition, this solution monoxone concentration is 60%～80%w/w, under 0 ℃～10 ℃ conditions, react 23～25h, centrifugal filtration reaction mash obtains solid then, with 75%～80% washing with alcohol solid 2～6 times, be neutralized to pH neutrality with dilute hydrochloric acid in the washing process, get carboxymethyl chitosan, dry;
(3) refining carboxymethyl chitosan
Under aseptic condition, above-mentioned carboxymethyl chitosan is fully dissolved with the aseptic apirogen water of 80～100 times of volumes, the elimination insoluble matter, with molecular cut off is 300,000 daltonian films to the operation of dialysing of carboxymethyl chitosan sugar aqueous solution, then with the progressively dilute filtration degerming of carboxymethyl chitosan sugar aqueous solution in the bag filter, final strength of fluid dilution is 0.1%w/v, then with the dehydrated alcohol of 2～4 times of volumes of this solution flocculation carboxymethyl chitosan, with the carboxymethyl chitosan vacuum drying after the flocculation, get purified carboxymethyl chitosan;
(4) preparation anti-adhesion gel
Under aseptic condition, take by weighing the refining carboxymethyl chitosan of step (3), prepare the anti-adhesion gel of anti-adhesion gel dynamic viscosity 800～3000 centipoises according to following ratio with pyrogen-free utensil:
1 part of refining carboxymethyl chitosan
20～30 parts of waters for injection.
3. the preparation method of surgical operation anti-adhesion gel as claimed in claim 2 is characterized in that, (degerming of dilute filtration described in the step 3) is to adopt 0.22 μ m filter membrane.
4. the preparation method of surgical operation anti-adhesion gel as claimed in claim 2 is characterized in that, (flocculates with dehydrated alcohol through 0.22 μ m membrane filtration described in the step 3).
5. surgical operation anti-adhesion gel preparation is characterized in that the described anti-adhesion gel of claim 1 is stirred, and abundant swelling then under aseptic condition, cannedly makes in the Dispoable medical syringe, preserves under 0 ℃～10 ℃ conditions.
6. surgical operation anti-adhesion gel preparation as claimed in claim 5 is characterized in that, described anti-adhesion gel canned in the Dispoable medical syringe loading amount specification be 1 milliliter～20 milliliters.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100144135A CN100490822C (en) | 2007-04-24 | 2007-04-24 | Gelatin for preventing conglutination in the surgical and the method for preparing the same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100144135A CN100490822C (en) | 2007-04-24 | 2007-04-24 | Gelatin for preventing conglutination in the surgical and the method for preparing the same |
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| Publication Number | Publication Date |
|---|---|
| CN101036667A true CN101036667A (en) | 2007-09-19 |
| CN100490822C CN100490822C (en) | 2009-05-27 |
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|---|---|---|---|
| CNB2007100144135A Expired - Fee Related CN100490822C (en) | 2007-04-24 | 2007-04-24 | Gelatin for preventing conglutination in the surgical and the method for preparing the same |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102258800A (en) * | 2010-05-25 | 2011-11-30 | 上海建华精细生物制品有限公司 | Compound wound-healing gel |
| CN102949754A (en) * | 2012-05-25 | 2013-03-06 | 江西圣济药业有限公司 | Uterine cavity hemostasis anti-adhersion temperature-sensitive gel and preparation method thereof |
| CN104337834A (en) * | 2014-11-10 | 2015-02-11 | 河北爱能生物科技有限公司 | Carboxymethyl chitosan clysis liquid |
| CN108159508A (en) * | 2018-01-03 | 2018-06-15 | 东南大学 | A kind of preparation method of anti-adhesion medical hydrogel material |
| CN112043879A (en) * | 2020-09-15 | 2020-12-08 | 山东奥能医疗科技有限公司 | Carboxymethyl chitosan surgical anti-adhesion gel and preparation method thereof |
| CN113332236A (en) * | 2020-03-03 | 2021-09-03 | 杭州协合医疗用品有限公司 | Preparation method of carboxymethyl chitosan anti-adhesion flushing fluid for surgical operation |
| CN116173316A (en) * | 2023-03-28 | 2023-05-30 | 赛克赛斯生物科技股份有限公司 | Anti-adhesion preparation, device, preparation method and application thereof |
-
2007
- 2007-04-24 CN CNB2007100144135A patent/CN100490822C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102258800A (en) * | 2010-05-25 | 2011-11-30 | 上海建华精细生物制品有限公司 | Compound wound-healing gel |
| CN102258800B (en) * | 2010-05-25 | 2015-04-08 | 上海建华精细生物制品有限公司 | Compound wound-healing gel |
| CN102949754A (en) * | 2012-05-25 | 2013-03-06 | 江西圣济药业有限公司 | Uterine cavity hemostasis anti-adhersion temperature-sensitive gel and preparation method thereof |
| CN104337834A (en) * | 2014-11-10 | 2015-02-11 | 河北爱能生物科技有限公司 | Carboxymethyl chitosan clysis liquid |
| CN104337834B (en) * | 2014-11-10 | 2017-06-30 | 河北爱能生物科技股份有限公司 | A kind of carboxymethyl chitosan Enema liquid |
| CN108159508A (en) * | 2018-01-03 | 2018-06-15 | 东南大学 | A kind of preparation method of anti-adhesion medical hydrogel material |
| CN113332236A (en) * | 2020-03-03 | 2021-09-03 | 杭州协合医疗用品有限公司 | Preparation method of carboxymethyl chitosan anti-adhesion flushing fluid for surgical operation |
| CN112043879A (en) * | 2020-09-15 | 2020-12-08 | 山东奥能医疗科技有限公司 | Carboxymethyl chitosan surgical anti-adhesion gel and preparation method thereof |
| CN116173316A (en) * | 2023-03-28 | 2023-05-30 | 赛克赛斯生物科技股份有限公司 | Anti-adhesion preparation, device, preparation method and application thereof |
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| Publication number | Publication date |
|---|---|
| CN100490822C (en) | 2009-05-27 |
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