CN106924809A - Filler under a kind of I-type collagen and liquid mucous membrane - Google Patents
Filler under a kind of I-type collagen and liquid mucous membrane Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2389/00—Characterised by the use of proteins; Derivatives thereof
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Abstract
The invention discloses filler under a kind of I-type collagen and liquid mucous membrane, wherein collagen has complete natural triple-helix structure, and wherein Hydroxyproline content is more than 11%.The I-type collagen and the I-type collagen powder prepared by described I-type collagen, it is particularly useful for making filler under liquid mucous membrane, filler can be used as the repair materials for swelling wound in agent and surgical procedure of focus in scope submucosa resection or scope submucosa decollement under gained liquid mucous membrane, supporting time length is reasonable, can be absorbed by tissue completely, have hemostasis concurrently simultaneously and repair energy function, application effect is very good.
Description
Technical field
The present invention relates to biomaterial field, under particularly a kind of I-type collagen, and liquid mucous membrane prepared therefrom
Filler.
Background technology
At present, the popularization of follow-up endoscopy, precancerous lesion gradually rises with early cancer recall rate.Scope submucosa is peeled off
Art (ESD) or scope submucosa resection (EMR) are increasingly becoming a kind of a kind of mark for cutting off alimentary canal precancerous lesion and early cancer
Quasi- minimally-invasive treatment means, it can be by lesion intactly en bloc resection, so as to greatly reduce the risk of tumor recurrence.
ESD operations there is also greater risk, it may occur however that some complication, mainly include Alimentary Tract Perforation and bleeding.Pin
There is this phenomenon of perforating to patient, in order that its more safe and convenience, majority scholar's research confirmation both at home and abroad at present, in hand
Carrying out submucosal injection before art excision can reduce the generation of such complication.
Studying the submucosal injection liquid being related at present has physiological saline, hypertonic saline, glucose, Glycerin Fructose, difference
Sodium Hyaluronate and hydroxymethyl cellulose, fibrinogen of concentration etc..But these submucosal injection liquid in clinical practice still
Come with some shortcomings.For example after physiological saline liquid is fast to surrounding tissue diffusion and maintains the time of lesion mucous membrane protuberance
It is short, most of local eminence shapes formed by physiological saline when resection operation has not been completed partial disappearance.
And can then there is different degrees of tissue damage effect in other parenteral solutions such as hypertonic saline.
Because in consideration of it, special propose the present invention.
The content of the invention
It is an object of the invention to provide a kind of new I-type collagen, the New function structure of I-type collagen is developed.
It is a further object of the present invention to provide new use of the above-mentioned new I-type collagen in terms of submucosal injection liquid is prepared
On the way.
Third object of the present invention is to provide a kind of new submucosal injection liquid, to overcome existing submucosal injection liquid
The problem for existing in use.
The present invention is achieved through the following technical solutions above-mentioned purpose：
The invention provides a kind of I-type collagen, collagen has complete natural triple-helix structure, wherein hydroxyl
Base proline content more than 11% (hydroxyproline accounts for the 9~13% of collagen in I-type collagen, referring to《The Chinese people
Republic's pharmaceuticals industry standard：The part of organizational project medical product the 6th：I-type collagen》).Research finds collagen heat
Good stability, space support persistent is moderate to focus protuberance action time length, it is not necessary to which the later stage takes out, and opponent
Oozing of blood plays timely anastalsis at art wound, contributes to the quick reparation of wound.
Based on these characteristics, the answering in filler under preparing liquid mucous membrane the invention provides above-mentioned I-type collagen
With.
Filler is to be injected into lesion submucosa under liquid mucous membrane, one is formed between lesion and muscularis propria and is sticked
Layer of liquid shim under film, lesion mucous membrane is held up, and the generation of perforation can be prevented when lesion mucous membrane is removed, anastalsis is played
And promote to be removed the healing on surface.Filler can be used at the digestive organs mucous membrane of generation lesion under liquid mucous membrane.
Although the biomaterial in the market with collagen as matrix is many, such as collagen protein sponge, absorbable collagen
Albumen suture, medical collagen membrane, collagen apply material, collagen implant (double U.S.s), medical collagen filler (skin U.S.A reaches)
Deng, but for ESD or EMR operations, both required under mucous membrane liquid cushion can during performing the operation continued support, require in hand again
Can be by tissue absorbed themselves without taking out to avoid causing secondary damage to patient, so existing collagen stroma after the completion of art
Biomaterial cannot all be applicable, and filler then meets such requirement under I-type collagen of the invention is prepared into liquid mucous membrane,
Duration is appropriate, and collagen can voluntarily degrade in vivo, and using effect is good.
Present invention also offers a kind of I-type collagen powder, it is best suited for preparing filler, preparation method under liquid mucous membrane
Specifically include following steps：
(1) during the I-type collagen described in claim 1 adds neutral buffered liquid, stir, be standing and soak for；
(2) formaldehyde is added, stirring carries out cross-linking reaction under the conditions of 35~39 DEG C；
(3) product is cleaned using neutral buffered liquid, then uses deionized water rinsing；
(4) freeze-drying, is crushed to grain diameter for 200~300 μm, obtains collagen protein powder.
Used as a kind of preferred scheme, above-mentioned I-type collagen powder, preparation method specifically includes following steps：
(1) during I-type collagen adds neutral buffered liquid, stir, be standing and soak for；
(2) formaldehyde is added, stirring carries out cross-linking reaction under the conditions of 35~39 DEG C；
(3) product is cleaned using neutral buffered liquid, then uses deionized water rinsing；
(4) freeze-drying, is crushed to grain diameter for 200~300 μm, obtains collagen protein powder.
Add neutral buffered liquid and be standing and soak for making the whole system of solution to be in the pH environment of stable homogeneous,
When being added thereto to the material of meta-acid or meta-alkali, certain cushioning effect can be played to its pH value, pH value is not caused very big
Change.
Because collagen is deposited certain hour and can be degraded in a liquid, cause the destruction of its triple-helix structure, make in fact
Border practical application weakens or loses.So needing to add formaldehyde to be crosslinked, can so extend its degradation time.It is not crosslinked
The filler for preparing of collagen from principle for also can to use, but because the collagen not being crosslinked drops in a liquid
Collagen after the relative crosslinking of solution is fast, therefore keeping life can be very short；Whether being crosslinked simultaneously can be to final liquid filler
Viscosity has some to influence.Neutral buffered liquid is cleaned and the purpose of deionized water rinsing is to remove the first do not participated in reaction and remain
Aldehyde.
Because collagen belongs to a kind of biomaterial very sensitive to temperature, will be denatured more than certain temperature, because
This crushes this material at present is carried out under the conditions of liquid nitrogen；Even if in addition under the conditions of liquid nitrogen, its toughness is still very big.Institute
With at present be liquid nitrogen under the conditions of grinding its average grain diameter can't be made to reach less than 150 μm.Therefore also need to described hereinafter
High-pressure homogeneous process.
The crosslinking temperature of I-type collagen is less than its denaturation temperature in the present invention, while after freeze-drying, at -196 DEG C
Hereinafter crushed, distinctive natural triple-helix structure retains in enabling I-type collagen, it is to avoid triple-helix structure is because of temperature
Too high generation denaturation of scattering, reaches more preferable using effect.
As a kind of preferred scheme, above-mentioned I-type collagen powder, the neutral buffered liquid by 0.01mol/L phosphoric acid hydrogen
Two sodium solutions and pH be 5~6 MES solution mix to pH be 7 after with deionized water dilute 20 times be prepared from.Because phosphoric acid hydrogen
Disodium solution concentration is too high or pH is too low, can cause collagenolysis, therefore using the disodium phosphate soln and pH of 0.01mol/L
Buffer solution is prepared for the MES solution mixing of 5-6.
Used as a kind of preferred scheme, above-mentioned I-type collagen powder, the quality of formaldehyde is used with step (1) in step (2)
Neutral buffered liquid volume ratio is 0.08%~0.30%.
Product does not have strict requirements for the degree of cross linking, but the suitably crosslinking of formaldehyde consumption can improve final liquid and fill out
The viscosity for filling agent extends the term of validity of product simultaneously.
Used as a kind of preferred scheme, above-mentioned I-type collagen powder, mixing speed is 180~300 revs/min in step (2),
Reaction time is 3~4h.Can make crosslinking more homogeneous under this reaction condition, reach more preferable cross-linking effect.
Used as a kind of preferred scheme, above-mentioned I-type collagen powder, freeze-drying is followed the steps below in step (4)：
A. precooling：Precooling 60min at prior to -40 DEG C, then at 150~180min of precooling at -20 DEG C, and keeps cold
The temperature of lyophilizer refrigerator is at -60~-50 DEG C；
B. dry：7h is dried prior to -10 DEG C, then 7h is dried in 0 DEG C, 8h is dried then at 5 DEG C, dry 8h in 10 DEG C, most
8h is dried after 1510 DEG C, 20h is dried in 20 DEG C；
Precooling and drying stage environment vacuum degree are 200~350 millitorrs.
First precooling is set, and re-dry can make the water content in the lyophilized sample of needs drop to less than 10%, so
The more conducively freeze grinding step of next step.
Used as a kind of preferred scheme, above-mentioned I-type collagen powder, the crushing of step (4) is crushed using freeze grinding, environment
Below -196 DEG C, grinding time is 10~12min to temperature.
Under extremely low temperature, sample can become fragile, it is easier to grind and reach required Particle size requirements；Enter at this temperature simultaneously
Row grinding makes the triple-helix structure of collagen not be subject to any destruction.
Present invention also offers filler under a kind of liquid mucous membrane, be by above-mentioned I-type collagen, or more any institute
The I-type collagen powder stated, is suspended in phosphate buffer or is suspended in physiological saline and be prepared from；Collagen in suspension
Average grain diameter be 50~150 μm.
Because clinically inject when need by institute matching used mucosectomy in conduit, need reach
Above-mentioned Particle size requirements.
As a kind of preferred scheme, filler under above-mentioned liquid mucous membrane, when using I-type collagen powder, first by I type glue
Former albumen powder is added in phosphate solution or physiological saline, below 0 DEG C of temperature, pressure be 800~1000bar under the conditions of enter
Row homogeneous to collagen particle diameter is down to 50~150 μm, obtains filler under liquid mucous membrane.
Temperature setting can ensure that albumen will not be denatured in preparation process below 0 DEG C；High pressure can reduce glue
The average grain diameter of former particle homogeneous.
Used as a kind of preferred scheme, filler under above-mentioned liquid mucous membrane, homogeneous is repeated 5~10 times.
Repeating homogeneous can make the average grain diameter of collagen particle collagen particle is preferably dispersed in solution in the lump
In.
The invention has the advantages that：
I-type collagen conduct of the present invention only containing natural triple-helix structure and Hydroxyproline content more than 11%
Raw material prepare filler under liquid mucous membrane, can be used as focus in scope submucosa resection or scope submucosa decollement
Protuberance agent, maintain sufficiently long time and smoothly implemented with ensureing to perform the operation and without multiple injection, surrounding tissue will not be caused
Damage, effectively reduce the complication such as bleeding and perforation；The repair materials of wound in surgical procedure are also used as, it is postoperative to send out
Blood, and the absorption that can be degraded in 30 days are born, without worrying that it produces harmful effect to tissue.
Specific embodiment
In order that those skilled in the art more fully understand the present invention program, below specific embodiment the present invention is made
It is further to describe in detail.
Embodiment one
The disodium phosphate soln of 0.01mol/L is taken, the MES solution of pH=6 is added thereto to, to pH of mixed to 7, will
20 times of mixed liquor deionized water dilution for being adjusted to neutrality is made neutral buffered liquid.
Take I-type collagen (the hydroxyproline content ＞ with natural triple-helix structure of 20g purity more than 99%
11%), it is placed in 600ml neutral buffered liquid, 5~10min is to uniform for stirring, is standing and soak for 1.5h.
To the formalin that 1.25ml 38.5% is added in neutral buffered liquid, stirring 7min makes to be well mixed, and is subsequently placed in
3h is crosslinked with 200 revs/min of speed stirring reaction in 37 DEG C of thermostat water baths.
Reaction takes out product after terminating, and washes 30min with buffer solution, then 1h is washed with deionized water.
Collagen after cleaning is carried out into freeze-drying, first the precooling 1h at -40 DEG C, then precooling 3h, phase at -20 DEG C
Between keep freeze drier refrigerator temperature at -60~-50 DEG C.
Freezing dry process dries 7h in -10 DEG C of dryings in 0 DEG C, and 8h is dried then at 5 DEG C, and 8h is dried in 10 DEG C, most after
15 DEG C dry 8h, and 20h is dried in 20 DEG C.Material moisture is 6% or so after drying.Environment vacuum in precooling and drying process
It is 200 millitorrs to spend.
Dried material is carried out into freeze grinding crushing below -196 DEG C, 10min is crushed, mesh screen is crossed, particle diameter is obtained
It is the I-type collagen powder of 200~300 μm of 0.08% formaldehyde crosslinking.
Embodiment two
The disodium phosphate soln of 0.01mol/L is taken, the MES solution of pH=6 is added thereto to, to pH of mixed to 7, will
20 times of mixed liquor deionized water dilution for being adjusted to neutrality is made neutral buffered liquid.
I-type collagen with natural triple-helix structure of the 20g purity more than 99% is taken, 600ml buffer solutions are placed in
In, 5~10min is to uniform for stirring, is standing and soak for 1.5h.
To the formalin that 1.56ml 38.5% is added in buffer solution, stirring 10min makes to be well mixed, and is subsequently placed in 37
3.5h is crosslinked with 220 revs/min of speed stirring reaction in DEG C thermostat water bath.
Collagen is taken out after end, washes 40min with buffer solution, then 1.5h is washed with deionized water.
Collagen is carried out into freeze-drying, the first precooling 1h at -40 DEG C, then the precooling 3h at -20 DEG C, period keeps cold
The temperature of lyophilizer refrigerator is at -60~-50 DEG C.
Freezing dry process dries 7h in -10 DEG C of dryings in 0 DEG C, and 8h is dried then at 5 DEG C, and 8h is dried in 10 DEG C, most after
15 DEG C dry 8h, and 20h is dried in 20 DEG C.Material moisture is 6% or so after drying.Environment vacuum in precooling and drying process
It is 300 millitorrs to spend.
Dried material is carried out into freeze grinding crushing below -196 DEG C, 11min is crushed, mesh screen is crossed, particle diameter is obtained
It is the I-type collagen powder of 200~300 μm of 0.1% formaldehyde crosslinking.
Embodiment three
The collagen powder obtained in 4g embodiments one or embodiment two is weighed, 100ml concentration is added to for 0.5mmol/L, pH
In=7.5 phosphate buffer, stir.
Then mixed liquor is carried out into cryogenic high pressure homogeneous, below 0 DEG C, homogenization pressure is 800bar to homogenizing temperature.Repeat
Homogenize 9 times.Collagen particle diameter is obtained at 50~150 μm, collagen concentration is filler under the liquid mucous membrane of 40mg/ml.
Example IV
The collagen powder obtained in 5g embodiments one or embodiment two is weighed, 100ml concentration is added to for 0.5mmol/L, pH
In=7.6 phosphate buffer, stir.
Then mixed liquor is carried out into cryogenic high pressure homogeneous, below 0 DEG C, homogenization pressure is 900bar to homogenizing temperature.Repeat
Homogenize 11 times.Collagen particle diameter is obtained at 50~150 μm, collagen concentration is filler under the liquid mucous membrane of 50mg/ml.
Embodiment five
The collagen powder obtained in 6g embodiments one or embodiment two is weighed, 100ml concentration is added to for 0.5mmol/L, pH
In=7.8 phosphate buffer, stir.
Then mixed liquor is carried out into cryogenic high pressure homogeneous, below 0 DEG C, homogenization pressure is 900bar to homogenizing temperature.Repeat
Homogenize 13 times.Collagen particle diameter is obtained at 50~150 μm, collagen concentration is filler under the liquid mucous membrane of 60mg/ml.
The different submucosal injection product filling effect contrast tables of table 1
Reference table 1, the other submucosal injection products of contrast for example physiological saline, hypertonic saline, glucose, Glycerin Fructose,
Sodium Hyaluronate and hydroxymethyl cellulose, fibrinogen of various concentrations etc., prepared by the type i collagen material that the present invention is provided
Filler plays the role of preferably hemostasis and promotes healing under liquid mucous membrane.Simultaneously because collagen is extracellular matrix
Filler also has bio-compatible under a kind of structural proteins, therefore the liquid mucous membrane of the type i collagen material preparation of present invention offer
Property, low immunogenicity, biodegradability.
Above to a kind of type i collagen material with triple-helix structure of high-purity provided by the present invention, one kind is by institute
Filler and preparation method thereof is described in detail under liquid mucous membrane prepared by the type i collagen material stated.It is used herein
Specific case is set forth to principle of the invention and implementation method, and the explanation of above example is only intended to help and understands this
The core concept of invention.It should be pointed out that for those skilled in the art, not departing from the principle of the invention
Under the premise of, some improvement and modification can also be carried out to the present invention, these are improved and modification also falls into the claims in the present invention
In protection domain.
Claims (10)
1. a kind of I-type collagen, it is characterised in that collagen has complete natural triple-helix structure, wherein hydroxyl
Proline content is more than 11%.
2. application of the I-type collagen described in claim 1 in filler under preparing liquid mucous membrane.
3. a kind of I-type collagen powder, preparation method specifically includes following steps：
(1) during the I-type collagen described in claim 1 adds neutral buffered liquid, stir, be standing and soak for；
(2) formaldehyde is added, stirring carries out cross-linking reaction under the conditions of 35~39 DEG C；
(3) product is cleaned using neutral buffered liquid, then uses deionized water rinsing；
(4) freeze-drying, is crushed to grain diameter for 200~300 μm, obtains collagen protein powder.
4. I-type collagen powder according to claim 3, it is characterised in that the neutral buffered liquid is by 0.01mol/L's
Disodium phosphate soln and pH be 5~6 MES solution mix to pH be 7 after with deionized water dilute 20 times be prepared from.
5. I-type collagen powder according to claim 3, it is characterised in that the quality and step of formaldehyde in step (2)
(1) neutral buffered liquid volume ratio used is 0.08%~0.30% in.
6. I-type collagen powder according to claim 3, it is characterised in that mixing speed is 180~300 in step (2)
Rev/min, the reaction time is 3~4h.
7. I-type collagen powder according to claim 3, it is characterised in that freeze-drying is according to following step in step (4)
Suddenly carry out：
A. precooling：Precooling 60min at prior to -40 DEG C, then at 150~180min of precooling at -20 DEG C, and keeps freezing dry
The temperature of dry machine refrigerator is at -60~-50 DEG C；
B. dry：7h is dried prior to -10 DEG C, then 7h is dried in 0 DEG C, 8h is dried then at 5 DEG C, 8h is dried in 10 DEG C, most after
15 DEG C dry 8h, and 20h is dried in 20 DEG C；
Precooling and drying stage environment vacuum degree are 200~350 millitorrs.
8. I-type collagen powder according to claim 3, it is characterised in that the crushing of step (4) uses freeze grinding powder
Broken, below -196 DEG C, grinding time is 10~12min to environment temperature.
9. filler under a kind of liquid mucous membrane, it is characterised in that as I-type collagen or claim described in claim 1
3~8 any described I-type collagen powder, are suspended in phosphate buffer or are suspended in physiological saline and be prepared from；It is outstanding
The average grain diameter of collagen is 50~150 μm in supernatant liquid.
10. filler under liquid mucous membrane according to claim 9, it is characterised in that when using I-type collagen powder,
During I-type collagen powder first is added into phosphate solution or physiological saline, below 0 DEG C of temperature, pressure be 800~
Carried out under the conditions of 1000bar it is high-pressure homogeneous be down to 50~150 μm to collagen average grain diameter, obtain filler under liquid mucous membrane.
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| CN201710167939.0A CN106924809B (en) | 2017-03-20 | 2017-03-20 | I type collagen and liquid submucosal filling agent |
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| CN201710167939.0A CN106924809B (en) | 2017-03-20 | 2017-03-20 | I type collagen and liquid submucosal filling agent |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107686517A (en) * | 2017-08-18 | 2018-02-13 | 北京华信佳音医疗科技发展有限责任公司 | The preparation of filler under a kind of liquid collagen mucous membrane |
| CN107812244A (en) * | 2017-10-25 | 2018-03-20 | 北京华信佳音医疗科技发展有限责任公司 | A kind of preparation of liquid collagen filler |
| CN112334164A (en) * | 2018-06-21 | 2021-02-05 | 联邦高等教育系统匹兹堡大学 | Use of ECM hydrogel of bladder as fluid cushion of esophageal submucosa |
| CN113133996A (en) * | 2020-01-20 | 2021-07-20 | 山东威高药业股份有限公司 | Use of acetylcysteine or its chemically acceptable salt/ester in preparation of isolated preparation of connective tissue |
| CN114366857A (en) * | 2022-02-08 | 2022-04-19 | 博纳格科技(天津)有限公司 | Preparation method of degradable artificial bone composite material |
| CN116115515A (en) * | 2022-05-18 | 2023-05-16 | 广州创尔生物技术股份有限公司 | Stable type I collagen-ionic matrix composite system and preparation method thereof |
| US12383243B2 (en) | 2018-06-21 | 2025-08-12 | University of Pittsburgh—of the Commonwealth System of Higher Education | Extracellular matrix (ECM) hydrogel as a submucosal fluid cushion |
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| US12383243B2 (en) | 2018-06-21 | 2025-08-12 | University of Pittsburgh—of the Commonwealth System of Higher Education | Extracellular matrix (ECM) hydrogel as a submucosal fluid cushion |
| CN113133996A (en) * | 2020-01-20 | 2021-07-20 | 山东威高药业股份有限公司 | Use of acetylcysteine or its chemically acceptable salt/ester in preparation of isolated preparation of connective tissue |
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| CN116115515A (en) * | 2022-05-18 | 2023-05-16 | 广州创尔生物技术股份有限公司 | Stable type I collagen-ionic matrix composite system and preparation method thereof |
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