CN107261207A - A kind of collagen gel and preparation method thereof - Google Patents
A kind of collagen gel and preparation method thereof Download PDFInfo
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- CN107261207A CN107261207A CN201710505107.5A CN201710505107A CN107261207A CN 107261207 A CN107261207 A CN 107261207A CN 201710505107 A CN201710505107 A CN 201710505107A CN 107261207 A CN107261207 A CN 107261207A
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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
- A61L27/24—Collagen
-
- 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
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
-
- 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
- A61L27/52—Hydrogels or hydrocolloids
-
- 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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
-
- 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
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- 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
- A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
-
- 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
-
- 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
- C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
-
- 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
-
- 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
- C08J2467/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J2467/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
-
- 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
- C08J2489/00—Characterised by the use of proteins; Derivatives thereof
Abstract
The invention discloses a kind of collagen gel and preparation method thereof, the raw material of following mass percent is included:Collagen solution 20~80%, PCL microballoons 80~20% and lidocaine 0~1%.The raw material that uses of collagen gel of the present invention for Wholly-degradable material, it can be fully absorbed after implantation human body, and PCL degradation cycle is longer, its degradation time can be up to 2 years, make the effect duration of collagen gel long, reduce the frequency of use to collagen gel.
Description
Technical field
The present invention relates to tissue engineering material technical field, in particular to a kind of collagen gel and its preparation
Method.
Background technology
It can subtract with advancing age and/or as the consequence of some diseases, including the human body soft tissue of muscle and fat
It is few, influence appearance and/or function.Now, it is of interest as increasing consumer to inject micro-shaping based on beauty, wherein
Most of market is occupied with creotoxin and hyaluronic acid, and creotoxin sheet, as a kind of neurotoxin, its used in amounts will be controlled strictly
System, develops incomplete domestic market, it is easy to trigger serious safety risk in medical and beauty treatment industry each side;Hyaluronic acid sheet
Body soak time is fast, and the duration is short, generally requires multiple injection and can be only achieved Expected Results.In addition also have collagen class or
Biomaterial class injection, these injections can not all meet the characteristics of completely absorbable, the duration is long simultaneously.
The beauty injection of in the market has some non-fully to can absorb, and potential safety hazard can be left after implantation human body.
Other absorbable beauty injection completely, its on degradation time often in 1 year even within half a year,
Effect duration is short, adds the frequency of injection of user.
The content of the invention
In view of this, a kind of collagen gel that the present invention is provided and preparation method thereof, preferably overcomes above-mentioned existing
The problem of with the presence of technology and defect, the raw material that the collagen gel is used are implanted into after human body for the material of Wholly-degradable
It can fully absorb, and the degradation cycle of polycaprolactone (PCL) is longer, makes the effect duration of collagen gel long, reduces
To the frequency of use of collagen gel.
A kind of collagen gel, includes the raw material of following mass percent:Collagen solution 20~80%, PCL are micro-
Ball 80~20% and lidocaine 0~1%.
Further, the mass percent of the collagen is more than or equal to 40%, the mass percent of the PCL microballoons
Less than or equal to 60%.
Further, the mass percent of the collagen is more than or equal to 55%, the mass percent of the PCL microballoons
Less than or equal to 45%, and the mass percent of the lidocaine is more than or equal to 0.1%.
Further, the collagen solution is the aqueous solution of Atelocollagen albumen, the Atelocollagen albumen
Mass percentage concentration be 1~30%.
Further, the particle size of the PCL microballoons is 20~75 μm.
Further, the particle size of the PCL microballoons is 35~45 μm.
Present invention also offers a kind of preparation method of collagen gel, the collagen gel is above-mentioned collagen
Protein gel, the preparation method includes:Each raw material is well mixed.
Further, each raw material is well mixed using sonic oscillation.
Further, the ultrasonic time is 5~15min, and the ultrasonic frequency is 15~30Hz.
Further, the PCL microballoons are prepared using supersonic spraying or microfluidic method, prepare the PCL micro-
The viscosity for the PCL raw materials that ball is used prepares the surfactant that the PCL microballoons are used for 40000~100000mPa.s
For the emulsion of polyvinyl alcohol, methylcellulose or carboxymethyl cellulose.
Compared with prior art, a kind of beneficial effect of collagen gel of the invention and preparation method thereof is:
(1) raw material that collagen gel of the invention is used is the material of Wholly-degradable, and being implanted into can be complete after human body
Absorb, and PCL degradation cycle is longer, its degradation time can be up to 2 years, make the effect duration of collagen gel
It is long, reduce the frequency of use to collagen gel.
(2) preparation method of collagen gel of the invention is simple, can obtain granularity by a variety of preparation technologies equal
One PCL microballoons, the longer collagen gel of effect duration is mixed to get with collagen solution.
To enable the above objects, features and advantages of the present invention to become apparent, preferred embodiment cited below particularly makees detailed
It is described as follows.
Embodiment
For the ease of understanding the present invention, technical scheme is elaborated with reference to the mode of embodiment,
Many details are elaborated in the following description to fully understand the present invention.
But the invention can be embodied in many other ways as described herein, those skilled in the art can be with
Similar improvement is done in the case of without prejudice to intension of the present invention, therefore the present invention is not limited to the specific embodiments disclosed below.
Unless otherwise defined, all technologies used herein and scientific terminology have and the common skill of art of the present invention
The identical implication that art personnel are generally understood that.When there is contradiction, the definition in this specification is defined.
Term as used herein:
" by ... prepare " it is synonymous with "comprising".Term "comprising" used herein, " comprising ", " having ", " containing "
Or its any other deformation, it is intended that cover including for non-exclusionism.For example, composition, step, method comprising listed elements,
Product or device are not necessarily limited to those key elements, but can include not expressly listed other key elements or such a composition, step
Suddenly, method, product or the intrinsic key element of device.
Conjunction " by ... constitute " exclude any key element do not pointed out, step or component.If be used in claim,
This phrase will make claim be closed, it is not included the material in addition to materials of those descriptions, but relative
Except customary impurities.When phrase " by ... constitute " be rather than immediately following theme in the clause that appears in claim main body after
When, it is only limited to the key element described in the clause;Other key elements be not excluded as the overall claim it
Outside.
Equivalent, concentration or other values or parameter are excellent with scope, preferred scope or a series of upper limit preferred values and lower limit
During the Range Representation that choosing value is limited, this, which is appreciated that, specifically discloses by any range limit or preferred value and any scope
All scopes that any pairing of lower limit or preferred value is formed, regardless of whether whether the scope separately discloses.For example, when open
Scope " when 1~5 ", described scope should be interpreted as including scope " 1~4 ", " 1~3 ", " 1~2 ", " 1~2 and 4~
5 ", " 1~3 and 5 " etc..When number range is described herein, unless otherwise indicated, otherwise the scope is intended to include its end
Value and all integers and fraction within the range.
"and/or" is used to represent that one of illustrated situation or both may to occur, for example, A and/or B includes (A
And B) and (A or B);
The invention provides a kind of collagen gel, the raw material of following mass percent is included:
Collagen solution 20~80% such as 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,
65%th, 70%, 75% or 80% etc.;
PCL microballoons 80~20% such as 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%,
30%th, 25% or 20% etc.;
Lidocaine 0~1% such as 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%,
0.9% or 1% etc..
Collagen (Collagen) is a kind of very important protein of human body, is primarily present in connective tissue.
It has very strong stretch capability, is the main composition of ligament and the Main Ingredients and Appearance of tendon forceps, collagen or extracellular matrix
Composition.It makes skin keep elastic, and the aging of collagen, then skin wrinkle is occurred.Collagen is a kind of biological
Polymer substance, is a kind of white, opaque, unbranched fibroid protein.It can supplement the battalion needed for skin layers
Support, strengthen Collage Activitv in skin, there is the effects such as skin care, anti-aging, beauty, wrinkle-chasing, hair care.The collagen of the present invention
The preferred pig derived collagen albumen of albumen, it is 5162 such as to purchase from SIGMA production code member, or is purchased from Sangon Biotech's
CAS numberings are 9007-34-5.
The PCL microballoons of the present invention to PCL raw materials using microemulsion method, supersonic spraying or microfluidic method by being prepared into
Arrive, PCL microballoons and collagen solution have a good compatibility, and be can be degradable raw material.
Lidocaine be also known as lidocaine, xylocaine, lidocaine hydrochloride, Lidocainum, Lighocaine,
Lignocaine, is local anesthetics of amide derivatives.Lidocaine can promote K+ in cardiac muscle cell to outflow in low dosage, reduction cardiac muscle
Self-disciplining, with the effect of anti-ventricular arythmia, lidocaine serves as the effect of antibiotic in the present invention.
Further, the mass percent of the collagen is more than or equal to 40%, the mass percent of the PCL microballoons
Less than or equal to 60%.
Further, the mass percent of the collagen is more than or equal to 55%, the mass percent of the PCL microballoons
Less than or equal to 45%, and the mass percent of the lidocaine is more than or equal to 0.1%.
Preferably, the collagen solution is the aqueous solution of Atelocollagen albumen, the Atelocollagen albumen
Mass percentage concentration be 1~30% such as 1%, 3%, 5%, 8%, 10%, 12%, 15%, 18%, 20%, 23%, 25%,
28% or 30% etc..
Preferably, the mass percentage concentration of the Atelocollagen albumen is 5~20%.
Preferably, the mass percentage concentration of the Atelocollagen albumen is 5~10%.
It should be noted that the immunogenicity of collagen mostlys come from the end peptide of collagen, Atelocollagen egg
Immunogenicity is eliminated in vain, so as to reduce allergy rate.
Preferably, the particle size of the PCL microballoons is 20~75 μm such as 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μ
M, 50 μm, 55 μm, 60 μm, 65 μm, 70 μm or 75 μm etc..
Preferably, the particle size of the PCL microballoons is 35~45 μm.
Present invention also offers a kind of preparation method of collagen gel described above, including:Each raw material is mixed equal
It is even.
Preferably, each raw material is well mixed using sonic oscillation.
Preferably, the ultrasonic time is 5~15min such as 5min, 8min, 10min, 12min or 15min etc., described
The frequency of ultrasound is 15~30Hz such as 15Hz, 18Hz, 20Hz, 23Hz, 25Hz, 28Hz or 30Hz.
Preferably, the PCL microballoons are prepared using supersonic spraying or microfluidic method, prepare the PCL microballoons
The viscosity of the PCL raw materials used for 40000~100000mPa.s such as 400000mPa.s, 500000mPa.s,
600000mPa.s, 700000mPa.s, 800000mPa.s, 900000mPa.s or 100000mPa.s etc., different viscosity distributions can
Hardness and degradation time for adjusting final microballoon, the beauty injection product for forming different size;Prepare the PCL
The surfactant that microballoon is used for polyvinyl alcohol (PVA), methylcellulose (MC) or carboxymethyl cellulose (CMC) emulsification
Liquid.
The technique for preparing PCL microballoons using supersonic spraying is as follows:
(1) configuration PCL solution and the emulsion as acceptable solution.
Above-mentioned PCL solution be PCL be dissolved in the PCL solution that DCM is prepared, the PCL solution concentrations be 1~5wt.% such as
1wt.%, 2wt.%, 3wt.%, 4wt.% or 5wt.%, preferably 2~4wt.%, more excellent is 2.wt%.
Above-mentioned emulsion is the aqueous solution of polyvinyl alcohol (PVA), methylcellulose (MC) or carboxymethyl cellulose (CMC),
Most preferably with the aqueous solution of methylcellulose (MC), 0.2~2g/100ml of concentration such as 0.2g/100ml of the emulsion,
0.5g/100ml, 0.8g/100ml, 1g/100ml, 1.2g/100ml, 1.5g/100ml, 1.8g/100ml or 2g/100ml, it is excellent
Elect 0.5~1g/100ml as, more excellent is 1g/100ml;The emulsion is prepared from by high shear emulsifying instrument.
(2) emulsion is placed in below ultrasonic spray apparatus nozzle and be stirred continuously with given pace, then by PCL solution
Atomized drop is emitted into from nozzle with given pace by ultrasonic spray apparatus, atomized drop falls into emulsion and separated out, through from
The heart acts on forming microballoon, and stand makes solvent volatilize at a certain temperature, and freeze-drying produces PCL microballoons after refiltering.
The stir speed (S.S.) of above-mentioned emulsion be 500~2000rpm such as 500rpm, 800rpm, 1000rpm, 1200rpm,
1500rpm, 1800rpm or 2000rpm etc., more excellent is 700~1200rpm, is slightly adjusted according to PCL molecular size ranges, molecule
Amount is bigger, and stir speed (S.S.) is bigger, when PCL molecular weight is 8w, and more excellent stir speed (S.S.) is 1000rpm.
Above-mentioned spray atomization speed be 0.1~50ml/min such as 0.1ml/min, 1ml/min, 5ml/min, 10ml/min,
15ml/min, 20ml/min, 30ml/min, 40ml/min or 50ml/min etc., preferably 1~20ml/min, it is more excellent be 5~
10ml/min。
Above-mentioned supersonic frequency is 1.6~2.0MHz.
Above-mentioned temperature when making the solvent volatilize is room temperature~50 DEG C, and time of repose is 12h.
The technique for preparing PCL microballoons using microfluidic method refers to the processing step of existing microfluidic method.However, it is desirable to say
Bright, microfluidic method of the invention is prepared in the technique of PCL microballoons, and micro-channel chip is used as using T-shaped channel chip;Will
PCL is dissolved in DCM (dichloromethane) as oil phase, the concentration of the oil phase is 1~5wt.% such as 1wt.%, 2wt.%, 3wt.%,
4wt.% or 5wt.%, preferably 2~4wt.%, more excellent is 4.wt%, and the oil phase is also dispersed phase;By surfactant such as
Tween-20/40/60/80, polyvinyl alcohol, the aqueous solution of methylcellulose or carboxymethyl cellulose most preferably use first as aqueous phase
The aqueous solution of base cellulose is as aqueous phase, and the concentration of the aqueous phase is 0.2~2g/100ml such as 0.2g/100ml, 0.5g/
100ml, 0.8g/100ml, 1g/100ml, 1.2g/100ml, 1.5g/100ml or 2g/100ml etc., preferably 0.5~1g/
100ml, more excellent is 1g/100ml, and the aqueous phase is also continuous phase.
Wherein, the flow velocity of dispersed phase be 0.1~2ml/h such as 0.1ml/h, 0.3ml/h, 0.5ml/h, 1ml/h, 1.2ml/h,
1.5ml/h or 2ml/h etc., the flow velocity of continuous phase is 0.1~10ml/h such as 0.1ml/h, 0.5ml/h, 1ml/h, 2ml/h, 3ml/
H, 5ml/h, 8ml/h or 10ml/h etc..
The PCL microballoons of the present invention can also be prepared using microemulsion method, and microemulsion method prepares PCL microballoons and uses existing skill
Operating procedure in art, can refer to Chinese patent 201410177510.6, does not repeat herein.But, using microemulsion method
PCL microballoon complex process is prepared, the microsphere particle size homogeneity of formation is poor, and use prepared by supersonic spraying or microfluidic method
The granularity uniformity of PCL microballoons is more preferable.
For the ease of understanding the present invention, technical scheme is further illustrated with reference to embodiment.Applicant
Statement, the present invention is illustrated by the following examples detailed process equipment and the technological process of the present invention, but not office of the invention
It is limited to these specific process equipments and technological process, that is, does not mean that the present invention should rely on following detailed process equipments and technique
Flow could be implemented.Person of ordinary skill in the field is it will be clearly understood that any improvement in the present invention, each to product of the present invention
The equivalence replacement of raw material and the addition of auxiliary element, the selection of concrete mode etc., all fall within protection scope of the present invention and openly
Within the scope of.
Embodiment 1
A kind of collagen gel, includes the raw material of following mass percent:20% collagen solution and 80%PCL are micro-
Ball.
The preparation method of the collagen gel comprises the following steps:
(1) by preparing PCL microballoons using supersonic spraying to viscosity for 40000mPa.s PCL raw materials;
(2) collagen solution and PCL microballoons are obtained into collagen gel using sonic oscillation is well mixed;Wherein,
The time of ultrasound is 5min, and ultrasonic frequency is 15Hz.
Embodiment 2
A kind of collagen gel, includes the raw material of following mass percent:40% collagen solution and 60%PCL are micro-
Ball.
The preparation method of the collagen gel comprises the following steps:
(1) by preparing PCL microballoons using supersonic spraying to viscosity for 70000mPa.s PCL raw materials;
(2) collagen solution and PCL microballoons are obtained into collagen gel using sonic oscillation is well mixed;Wherein,
The time of ultrasound is 10min, and ultrasonic frequency is 18Hz.
Embodiment 3
A kind of collagen gel, includes the raw material of following mass percent:55% collagen solution and 45%PCL are micro-
Ball.
The preparation method of the collagen gel comprises the following steps:
(1) by preparing PCL microballoons using supersonic spraying to viscosity for 90000mPa.s PCL raw materials;
(2) collagen solution and PCL microballoons are obtained into collagen gel using sonic oscillation is well mixed;Wherein,
The time of ultrasound is 12min, and ultrasonic frequency is 20Hz.
Embodiment 4
A kind of collagen gel, includes the raw material of following mass percent:65% collagen solution and 35%PCL are micro-
Ball.
The preparation method of the collagen gel comprises the following steps:
(1) by preparing PCL microballoons using supersonic spraying to viscosity for 100000mPa.s PCL raw materials;
(2) collagen solution and PCL microballoons are obtained into collagen gel using sonic oscillation is well mixed;Wherein,
The time of ultrasound is 15min, and ultrasonic frequency is 23Hz.
Embodiment 5
A kind of collagen gel, includes the raw material of following mass percent:20% collagen solution, 79%PCL are micro-
Ball and 1% lidocaine.
The preparation method of the collagen gel comprises the following steps:
(1) by preparing PCL microballoons using supersonic spraying to viscosity for 50000mPa.s PCL raw materials;
(2) collagen solution, PCL microballoons and lidocaine are obtained collagen and coagulated using sonic oscillation is well mixed
Glue;Wherein, the ultrasonic time is 8min, and ultrasonic frequency is 25Hz.
Embodiment 6
A kind of collagen gel, includes the raw material of following mass percent:40% collagen solution, 59.5%PCL
Microballoon and 0.5% lidocaine.
The preparation method of the collagen gel comprises the following steps:
(1) by preparing PCL microballoons using supersonic spraying to viscosity for 60000mPa.s PCL raw materials;
(2) collagen solution and PCL microballoons are obtained into collagen gel using sonic oscillation is well mixed;Wherein,
The time of ultrasound is 10min, and ultrasonic frequency is 28Hz.
Embodiment 7
A kind of collagen gel, includes the raw material of following mass percent:55% collagen solution, 44.7%PCL
Microballoon and 0.3% lidocaine.
The preparation method of the collagen gel comprises the following steps:
(1) by preparing PCL microballoons using supersonic spraying to viscosity for 70000mPa.s PCL raw materials;
(2) collagen solution and PCL microballoons are obtained into collagen gel using sonic oscillation is well mixed;Wherein,
The time of ultrasound is 5min, and ultrasonic frequency is 15Hz.
Embodiment 8
A kind of collagen gel, includes the raw material of following mass percent:65% collagen solution, 34.9%PCL
Microballoon and 0.1% lidocaine.
The preparation method of the collagen gel comprises the following steps:
(1) by preparing PCL microballoons using supersonic spraying to viscosity for 80000mPa.s PCL raw materials;
(2) collagen solution and PCL microballoons are obtained into collagen gel using sonic oscillation is well mixed;Wherein,
The time of ultrasound is 12min, and ultrasonic frequency is 30Hz.
The raw material that collagen gel prepared by above-described embodiment 1~8 is used is implanted into people for the material of Wholly-degradable
It can be fully absorbed after body, and PCL degradation cycle is longer, its degradation time can be up to 2 years, make the effect of collagen gel
Duration is long, reduces the frequency of use to collagen gel.
The preferred embodiments of the present invention are above are only, are not intended to limit the invention, for those skilled in the art
For member, inventive formulation and preparation technology can have various modifications and variations.Within the spirit and principles of the invention, institute
Any modification, equivalent substitution and improvements of work etc., should be included in the scope of the protection.
Claims (10)
1. a kind of collagen gel, it is characterised in that:Include the raw material of following mass percent:Collagen solution 20~
80%th, PCL microballoons 80~20% and lidocaine 0~1%.
2. collagen gel according to claim 1, it is characterised in that:The mass percent of the collagen is more than
Equal to 40%, the mass percent of the PCL microballoons is less than or equal to 60%.
3. collagen gel according to claim 1, it is characterised in that:The mass percent of the collagen is more than
Equal to 55%, the mass percent of the PCL microballoons is less than or equal to 45%, and the mass percent of the lidocaine is more than
Equal to 0.1%.
4. collagen gel according to claim 1, it is characterised in that:The collagen solution is Atelocollagen
The aqueous solution of albumen, the mass percentage concentration of the Atelocollagen albumen is 1~30%.
5. collagen gel according to claim 1, it is characterised in that:The particle size of the PCL microballoons be 20~
75μm。
6. collagen gel according to claim 5, it is characterised in that:The particle size of the PCL microballoons be 35~
45μm。
7. a kind of preparation method of collagen gel, it is characterised in that:The collagen gel is appointed in claim 1-6
Collagen gel described in one, the preparation method includes:Each raw material is well mixed.
8. the preparation method of collagen gel according to claim 7, it is characterised in that:Each raw material is shaken using ultrasound
Swing well mixed.
9. the preparation method of collagen gel according to claim 8, it is characterised in that:The ultrasonic time is 5
~15min, the ultrasonic frequency is 15~30Hz.
10. the preparation method of collagen gel according to claim 7, it is characterised in that:The PCL microballoons are using super
Sound spray-on process or microfluidic method are prepared, prepare the viscosity for the PCL raw materials that the PCL microballoons are used for 40000~
100000mPa.s, prepares the surfactant that the PCL microballoons are used fine for polyvinyl alcohol, methylcellulose or carboxymethyl
Tie up the emulsion of element.
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CN110404109A (en) * | 2019-08-15 | 2019-11-05 | 深圳兰度生物材料有限公司 | Soft tissue filler and preparation method thereof |
CN110638684A (en) * | 2019-09-02 | 2020-01-03 | 深圳兰度生物材料有限公司 | Injectable collagen composition and preparation method thereof |
CN110559489A (en) * | 2019-09-25 | 2019-12-13 | 广州益诚生物科技有限公司 | Injection filler |
CN110559489B (en) * | 2019-09-25 | 2021-08-27 | 广州益诚生物科技有限公司 | Injection filler |
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