CN107213028A - A kind of collagen implant and preparation method thereof - Google Patents
A kind of collagen implant and preparation method thereof Download PDFInfo
- Publication number
- CN107213028A CN107213028A CN201710383159.XA CN201710383159A CN107213028A CN 107213028 A CN107213028 A CN 107213028A CN 201710383159 A CN201710383159 A CN 201710383159A CN 107213028 A CN107213028 A CN 107213028A
- Authority
- CN
- China
- Prior art keywords
- collagen
- preparation
- implant
- phosphoric acid
- crosslinking agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
-
- 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
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/08—Radiation
- A61L2/081—Gamma radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
Abstract
The invention provides a kind of collagen implant, in percentage by weight, including：The phosphoric acid physiological buffer of 2 8% collagen, 0.1 0.5% additive, and surplus.Present invention also offers the preparation method of the collagen implant, including：Collagen is dispersed in phosphoric acid physiological buffer, and adds additive；Then carry out emulsifying processing and obtain product.The collagen implant of the present invention is sterile, safe, is easy to use, the term of validity is long, good biocompatibility.
Description
Technical field
The present invention relates to medical and beauty treatment fields, in particular it relates to a kind of collagen implant and its preparation side
Method.
Background technology
With the raising of quality of life, people, which not only pursue, to live healthy, more pursues and lives beautiful.People find peace
Entirely, mode effectively, economic mitigates aging sign, reduces face wrinkles, changes appearance.Medical treatment relatively safe and effective in recent years
Beauty mode is in facial soft tissue direct injection filler, repairing skin tissue's defect.Injection beautifying technique has become soft
One of main project of tissue filling beauty treatment, it is not operated on, bloodless minimal invasive and the features such as easy to operate, instant effect
Praised highly by numerous people seeking beauties.
Collagen class product is divided into animal sources and Ren Yuan, and animal derived collagen may cause rejection, typically be both needed to elder generation
Allergy skin test is carried out, often has animal collagen implant product to cause bleeding spot, the complication report such as granulation knurl.People's self collagen is produced
Product, immunological rejection is low, it is not necessary to carry out skin test test, but the product manufacturing cycle of current patent report is longer, produces work
Skill is complex, and equipment requirement is higher, and product cost is higher, and the deficient validity.
The Chinese invention patent application of Application No. 200810007484.7 discloses a kind of using human hair keratin preparation
The method of soft tissue filling material, specifically by the use of human hair stage casing as raw material, through over cleaning, bleaching, attrition process, it is lyophilized,
Packaging, 60Coradiation processing, powder homogenate and liquid human hair keratin particle are prepared into by human hair.The invention raw material sources by
Limit, it is difficult to industrialize, protein body is larger, injection pain is obvious；And foreign protein do not carry out immunogenicity in terms of processing, make
There is higher-security risk for packing material.
The Chinese invention patent application of Application No. 200810147082.7 disclose a kind of long-acting type collagen and its
Manufacture method, be specifically by pigskin through striking off excess tissue, remove grease, swelling, digestion, centrifuge, saltout, collect under
Collagen can be obtained after layer sediment, freeze-drying, then the collagen is mixed with γ-poly- Vetsin (γ-PGA), together
When add and glutaraldehyde solution and stir, carry out first and be crosslinked, repeat the addition glutaraldehyde solution and stir, carry out the
After secondary cross-linking, you can obtain the long-acting type collagen, the problem of its RT that can solve collagen is too short, but must
Injection must be usually supplemented, the glutaraldehyde of residual high concentration is additionally, there may be, has the shortcomings that bio-toxicity can be detrimental to health.
The content of the invention
It is an object of the invention to the defect for prior art, there is provided a kind of collagen implant and its preparation side
Method.
On the one hand, the invention provides a kind of collagen implant, in percentage by weight, including：2-8% glue
The phosphoric acid physiological buffer of former albumen, 0.1-0.5% additive, and surplus.
Foregoing collagen implant, the collagen is the recombination human source collagen obtained using microbe fermentation method
Albumen.
Foregoing collagen implant, the collagen is to handle obtained modified collagen egg by chemical crosslink technique
In vain, and the degree of cross linking be 50-90%.
Foregoing collagen implant, the additive is sodium carboxymethylcellulose, sodium lactate, Sodium Hyaluronate, sea
Any one or more in mosanom.
Also contain 0.25-0.35% lidocaines in foregoing collagen implant, the phosphoric acid physiological buffer.
On the other hand, the invention provides the preparation method of collagen implant, including：Collagen is dispersed in phosphorus
In sour physiological buffer, and add additive；Implant is obtained with subsequent progress emulsifying processing.
Foregoing preparation method, the collagen is the recombination human source collagen obtained using microbe fermentation method.
Foregoing preparation method, before collagen is dispersed in phosphoric acid physiological buffer, first to the collagen egg
It is handled as follows in vain：
The collagen is added in crosslinking agent and carries out crosslinking Treatment, crosslinking agent and the modified adhesive to obtaining then is removed
Former albumen is washed.
Foregoing preparation method, the crosslinking agent is BDDE, glutaraldehyde, Geniposide or carbonization
Diimine；The concentration of the crosslinking agent is 0.05-0.5mol/L.
Foregoing preparation method, the crosslinking agent is with the collagen according to 5-10:1 is reacted.
Foregoing preparation method, the treatment temperature of the crosslinking Treatment is 18-28 DEG C, and processing time is 6-20 hours.
Foregoing preparation method, the washing is cleaned 3-5 times with purified water or phosphoric acid physiological buffer, each 10-15
Minute.
Foregoing preparation method, after emulsifying processing, further comprises：Implant is filling in pre- embedding injection
In device, then sterilizing, for disposable.
Foregoing preparation method, the sterilizing is to use Co 60 to carry out irradiation sterilization with 15-30kGy irradiation dose.
Relative to prior art, collagen implant of the invention and preparation method thereof has the advantages that：
1. the collagen that the present invention is used is with the recombination human source collagen of the method microbial fermentation acquisition of genetic engineering
Egg, its stability is good, purity is high, apyrogeneity risk.
2. processing is modified to collagen using chemical crosslink technique, improves product degradation resistance, increase clinic makes
Use advantage.
3. the product that inoculated is honored as a queen is sterilized using 60Coradiation ensures the sterile level (10 of product-6), it is ensured that use safety
Property.
Brief description of the drawings
Fig. 1 represents to carry out the knot obtained by pushing force test using the collagen implant sample of the embodiment of the present invention 1
Really, wherein, ordinate be pushing force size, unit N；Abscissa is propulsion time, unit s.
Fig. 2 is represented obtained by the collagen implant sample progress efficacy experiment using the embodiment of the present invention 1
Result, wherein, w represents all numbers, and such as 1w represents the 1st week, by that analogy.
Embodiment
In order to be fully understood by the purpose of the present invention, feature and effect, by following embodiments, detailed is made to the present invention
Describe in detail bright.The process of the present invention is in addition to the description below, and remaining is using the conventional method or device of this area.
According to an aspect of the present invention, the invention provides a kind of collagen implant, in percentage by weight,
Including：The phosphoric acid physiological buffer of 2-8% collagen, 0.1-0.5% additive, and surplus.Preferably, the collagen egg
White implant, in percentage by weight, including：3.5-5% collagen, 0.1-0.25% additive, and surplus
Phosphoric acid physiological buffer.
Wherein, the collagen that the present invention is used is preferably the recombination human source collagen egg obtained using microbe fermentation method
In vain, it is for instance possible to use following method is obtained：Pichia yeast engineering is built, the high expression Pichia yeast engineering of screening is carried out
Fermenting and producing, ultrafiltration system concentration and ion-exchange chromatography etc. carry out collagen purifying, and collagen solution is through 0.22um films
Freezed after filtering, it is the recombination human source collagen available for the present invention to obtain collagen sponge.Specifically refer to Application No.
The patent of invention Shen of the 201610388271.8th, entitled " a kind of recombination human source collagen and its encoding gene and preparation method "
Please, the patent application is integrally incorporated in the application by reference.This collagen activity is high, virus-free residual, nothing
Immunogenicity, endotoxin-free, are pure biological agents, will not also produce pyrogen risk, and good biocompatibility, safe.
It is highly preferred that foregoing recombination human source collagen, which first passes through chemical crosslink technique processing, obtains modified collagen albumen,
It is used further to afterwards in the present invention.Wherein, the degree of cross linking for handling obtained modified collagen albumen by chemical crosslink technique is 50-
90%, preferably 70-80%.
Inventor is had found by studying, when the degree of cross linking of modified collagen albumen is not less than 50%, its degraded in vivo
Time can reach 6 months or longer, also, by research, inventor sums up following rule：
| The degree of cross linking | Degradation time in vivo |
| 50% | 6~7 months |
| 60% | 7~August |
| 70% | 9~October |
| 80% | 10~December |
In addition, it is more white bright by modified collagen color and luster, and hydrophobicity enhancing, it is easy to later stage emulsifying.
Wherein, foregoing additive is sodium carboxymethylcellulose, sodium lactate, (preferred molecular weight is 160- to Sodium Hyaluronate
180kDa), any one or more in sodium alginate etc..Their main function be improvement and regulation implant viscosity with
And realize homogeneity and applicability etc..These materials can pass through conventional acquisition purchased in market.
Wherein, phosphoric acid physiological buffer is phosphate buffer or phosphate buffer (Phosphate Buffered
Saline, abbreviation PBS), it is a conventional cushioning liquid for biological study.It is contained in a kind of water base salting liquid
Sodium chloride, phosphate helps to maintain constant osmotic pressure and pH value, its main function is to make the pH value of collagen implant
It is suitable for implantation human body or animal body.In actual production, those skilled in the art can configure phosphoric acid physiology as needed and delay
Fliud flushing.Preferably, a certain amount of lidocaine is also contained in phosphoric acid physiological buffer, for example, the present invention, which can be used, contains 0.25-
The phosphoric acid physiological buffer of 0.35 weight % (0.3 weight %) lidocaine, lidocaine has the effect of local anaesthesia, had
The characteristics of anesthesia onset is fast, the appropriate lidocaine of present invention addition can be effectively increased product clinical applicability, reduce pain, just
Operated in user.
The collagen implant that the present invention is provided is applied to medical and beauty treatment fields, is primarily adapted for use in Soft-tissue operation neck
Domain, mainly for facial wrinkles (for example, glabella line, wrinkles on one's forehead and crow's feet etc.), scar and other soft tissues that need to be filled
Position etc., with easy to use, safe, the long advantage of the term of validity.
According to another aspect of the present invention, the invention provides the preparation method of above-mentioned collagen implant, including：
Collagen is dispersed in phosphoric acid physiological buffer by above-mentioned percentage by weight, and adds additive；Then carry out homogenized milk
Change processing obtains product.
Preferably, the collagen is the recombination human source collagen obtained using microbe fermentation method.It is highly preferred that
The recombination human source collagen is the modified collagen albumen handled by chemical crosslink technique, and the degree of cross linking is 50-90%.
In a kind of preferred embodiment, the preparation method of collagen implant of the invention, including：
(1) the recombination human source collagen for obtaining microbe fermentation method adds in crosslinking agent and carries out crosslinking Treatment, then
Remove crosslinking agent and obtained modified collagen albumen is washed, it is lyophilized to obtain collagen protein powder.
Wherein, crosslinking agent is BDDE, glutaraldehyde, Geniposide or carbodiimides；The present invention
In the crosslinking agent mentioned both refer to the cross-linking agent solution for being configured to solution, concentration is 0.05-0.5mol/L.
Wherein, the crosslinking agent and the collagen are according to 5-10:1 is reacted., it is, according to by 1 gram of collagen
The ratio that albumen is added in 5-10 milliliters of crosslinking agents.
Wherein, crosslinking Treatment is handled 6-20 hours at a temperature of 18-28 DEG C.
Wherein, it is to be separated off with 1000-10000rpm centrifugation rate by ultracentrifugal mode to remove crosslinking agent
Supernatant.
Wherein, washing is cleaned 3-5 times with purified water or phosphoric acid physiological buffer, each 10-15 minutes.
(2) according to the percentage by weight in first aspect present invention, collagen protein powder is dispersed in containing 0.3% benefit card
In the phosphoric acid physiological buffer of cause, and additive is added, be fully swelled and be uniformly mixing to obtain mixture.
Wherein, additive is any one in sodium carboxymethylcellulose, sodium lactate, Sodium Hyaluronate, sodium alginate etc.
Or it is a variety of.These materials can pass through conventional acquisition purchased in market.
(3) emulsifying processing and packing and sterilizing.
Emulsifying processing is carried out to said mixture using high pressure Microfluidizer and mulser, it is then filling in pre-
In encapsulated injector, pre-encapsulated injector syringe needle size uses 27-30G, the volume of pre-encapsulated injector can for 1ml, 2ml,
5ml etc..And use Co 60 to be sterilized with 15-30kGy irradiation dose, for disposable.The product that inoculated is honored as a queen is adopted
Sterilized with 60Coradiation and ensure the sterile level (10 of product-6), it is ensured that safety in utilization.
The sample good biocompatibility prepared according to the method for the invention, with good moistening effect；While product
Uniformity is reliable after homogenize process, is easy to clinician to operate with；The lidocaine of addition significantly reduces patient's pain；
Final technique uses aseptic process, and Product Safety is effectively ensured.
Embodiment
The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to described reality
Apply among a scope.The experimental method of unreceipted actual conditions in the following example, conventionally and condition, or according to business
Product specification is selected.The collagen used in the following example is to use Application No. 201610388271.8, entitled " one
What the method disclosed in the application for a patent for invention of kind recombination human source collagen and its encoding gene and preparation method " was prepared
Recombination human source collagen, by SEQ ID NO：Amino acid sequence composition shown in 1, confirms its molecular weight about 38kD, purity
About 99.2%.
Embodiment 1
The composition of the collagen implant of the present embodiment is following (% represents percentage by weight)：
Modified collagen albumen by crosslinking Treatment：4.5%, its degree of cross linking is 67%；Sodium Hyaluronate：0.1%；With it is remaining
The sodium phosphate buffer containing 0.3% lidocaine of amount.
The preparation method of the collagen implant of the present embodiment is as follows：
(1) by collagen with 1：10 (w/v) ratios add concentration in 0.1mol/L glutaraldehyde cross-linking agent solution, to hand over
Connection time 12h, 20 DEG C of operative temperature, the degree of cross linking of obtained modified collagen albumen is 67%；With 5000rpm speed in centrifuge
Rate is centrifuged and removes supernatant, then rinses modified collagen albumen with clear water, is rinsed 3 times altogether, each 15min；Using cold
Lyophilizer freezes modified collagen protein powder.
(2) 4.5% collagen protein powder is dispersed in the sodium phosphate buffer containing 0.3% lidocaine, added simultaneously
0.1% Sodium Hyaluronate, is fully swelled, and is uniformly mixing to obtain mixture；
(3) emulsifying processing is carried out to said mixture using high pressure Microfluidizer and mulser, it is then filling
In pre-encapsulated injector, the dosage of every is 1ml, and uses Co 60 to be sterilized with 15kGy irradiation dose, for once
Property is used.
Embodiment 2
The composition of the collagen implant of the present embodiment is following (% represents percentage by weight)：
Modified collagen albumen by crosslinking Treatment：3.5%, its degree of cross linking is 75%；Sodium carboxymethylcellulose：
0.15%；With the sodium phosphate buffer containing 0.3% lidocaine of surplus.
The preparation method of the collagen implant of the present embodiment is as follows：
(1) by collagen with 1：5 (w/v) ratios add the carbodiimide cross-linker solution that concentration is 0.2mol/L
In, crosslinking time 20h, 25 DEG C of operative temperature, the degree of cross linking of obtained modified collagen albumen is 75%；In centrifuge with
1000rpm speed is centrifuged and removes supernatant, then rinses modified collagen albumen with clear water, altogether rinsing 3 times, every time
15min；Modified collagen protein powder is freezed using freeze drier.
(2) 3.5% collagen protein powder is dispersed in the sodium phosphate buffer containing 0.3% lidocaine, added simultaneously
0.15% sodium carboxymethylcellulose, is fully swelled, and is uniformly mixing to obtain mixture；
(3) emulsifying processing is carried out to said mixture using high pressure Microfluidizer and mulser, it is then filling
In pre-encapsulated injector, the dosage of every is 2ml, and uses Co 60 to be sterilized with 20kGy irradiation dose, for once
Property is used.
Embodiment 3
The composition of the collagen implant of the present embodiment is following (% represents percentage by weight)：
Modified collagen albumen by crosslinking Treatment：5%, its degree of cross linking is 78%；Sodium lactate：0.1%；Hyaluronic acid
Sodium：0.15%；With the sodium phosphate buffer containing 0.3% lidocaine of surplus.
The preparation method of the collagen implant of the present embodiment is as follows：
(1) by collagen with 1：15 (w/v) ratios add concentration in 0.5mol/L Geniposide cross-linking agent solution, to hand over
Connection time 8h, 4 DEG C of operative temperature, the degree of cross linking of obtained modified collagen albumen is 78%；With 10000rpm speed in centrifuge
Rate is centrifuged and removes supernatant, then rinses modified collagen albumen with clear water, is rinsed 3 times altogether, each 15min；Using cold
Lyophilizer freezes modified collagen protein powder.
(2) 5% collagen protein powder is dispersed in the sodium phosphate buffer containing 0.3% lidocaine, added simultaneously
0.1% sodium lactate and 0.15% Sodium Hyaluronate, are fully swelled, are uniformly mixing to obtain mixture；
(3) emulsifying processing is carried out to said mixture using high pressure Microfluidizer and mulser, it is then filling
In pre-encapsulated injector, the dosage of every is 5ml, and uses Co 60 to be sterilized with 25kGy irradiation dose, for once
Property is used.
Embodiment 4-7
As shown in table 1, preparation method is similar with embodiment 1, difference for the composition of embodiment 4-7 collagen implant
Place simply adjusts specific crosslinking time and temperature according to the degree of cross linking.
Table 1
Effect detection embodiment
Collagen implant prepared by the various embodiments described above can be used for facial decree line, crow's feet, wrinkles on one's forehead or scar
And other feasible soft tissue position fillings etc., with easy to use, safe, the advantage such as term of validity length.While inventor
Also carry out that multinomial detection is security verified and validity to the implant of the present invention, it is specific as follows：
1) Sterility testing
Sterility testing is carried out to embodiment 1-7 collagen implant, it is specially sterile to take outer packing apart, it is inoculated with respectively
It is enough to submerge in the appropriate culture medium of test sample in each pipe, according to《Pharmacopoeia of People's Republic of China》(version in 2010) three annex
Method as defined in Ⅻ A is determined, and is as a result shown sterile.
2) cytotoxin is detected
The sample of the collagen implant of Example 1 is according to evaluation method specified in GB/T 16886.5-2003
Evaluated, be specially：The eugonic L929 cells collected by trypsinisation of 48-72h will be passed on, will be matched somebody with somebody with DMEM in high glucose culture medium
It is set to 1 × 104/ ml cell suspension, is seeded in 96 orifice plates, per the μ l of hole 200.Sample is according to 1:9 ratios extract (w/w), leaching
Matter is recommended for the DMEM in high glucose nutrient solution containing 10% NBCS, extraction temperature is 37 DEG C, and extraction time is 24h.Will experiment
Group, blank group and positive controls are separately added into cell suspension, are placed in 37 DEG C, 5%CO2, saturated humidity cell culture incubator
Culture, daily micro- Microscopic observation cellular morphology.When cultivating 5d, surveyed using enzyme-linked immunosorbent assay instrument under 490nm wavelength
Each hole absorbance (OD values), is returned to zero with blank zeroing hole OD values, averages and record.According to the absorbance average meter of each group
The relative appreciation rate of cell is calculated, as a result as shown in table 2.
Cell-cytotoxic reaction grade scale
Table 2
| Sample number into spectrum | 1 | 2 | 3 | 4 | 5 |
| Cell proliferation rate | 91% | 92% | 91% | 88% | 89% |
It can be seen from cell-cytotoxic reaction grade scale, cytotoxicity is 1 grade, illustrates that material safety is high, without substantially
Cytotoxicity.Inventor has also carried out above-mentioned cytotoxin detection, the similar result also obtained to embodiment 2-7 sample.
3) pushing force
The sample of the collagen implant of Example 1, with constant speed pushing syringe pushing ram, syringe needle
Head is 30G, and driving velocity 30mm/min, testing result is that pushing force is respectively less than 15N (as shown in Figure 1), meets surgical operation and fits
Chirality is required.Inventor has also carried out pushing force to embodiment 2-7 sample, the similar result also obtained.
4) efficacy
The intracutaneous implantation experiment of rat detects secure sample and validity, and specific method is：Rat back both sides carry out sample
Product are injected, and wherein experimental group uses the collagen implant sample of the embodiment of the present invention 1, and opposite side control group is double U.S. collagens
Albumen implant (from double beautiful (Sunmax) biotech inc in Taiwan, model is double U.S. No. 1 for purchase), each injection
Point is 0.1ml, is drawn materials respectively at 1w, 16w, 32w, opens observation material degradation situation on the inside of rat back corium, as a result
As shown in Figure 2.
Can be seen that by Fig. 2 results, control group degraded be significantly faster than that experimental group, control group Partial digestion during 16w, experimental group without
Obvious degradation, experimental group sample naked eyes are still high-visible during 32w, and control group material is degradable completely.Experimental result
Prove, the collagen implant term of validity of the invention is longer and good biocompatibility.
Above-described embodiment is the present invention preferably embodiment, but present aspect embodiment not by above-described embodiment
Limitation, other any Spirit Essences without departing from the present invention and the replacement made under principle, modification, combine, change, simplification
Deng should be equivalent substitute mode, be included within protection scope of the present invention.
Claims (14)
1. a kind of collagen implant, it is characterised in that in percentage by weight, including：2-8% collagen,
0.1-0.5% additive, and surplus phosphoric acid physiological buffer.
2. collagen implant according to claim 1, it is characterised in that the collagen is using microorganism hair
The recombination human source collagen that ferment method is obtained.
3. collagen implant according to claim 1 or 2, it is characterised in that the collagen is by chemistry
The modified collagen albumen that cross-linking method processing is obtained, and the degree of cross linking is 50-90%.
4. the collagen implant according to claim any one of 1-3, it is characterised in that the additive is carboxymethyl
Any one or more in sodium cellulosate, sodium lactate, Sodium Hyaluronate, sodium alginate.
5. the collagen implant according to claim any one of 1-4, it is characterised in that the phosphoric acid physiological buffer
In also contain 0.25-0.35% lidocaines.
6. the preparation method of the collagen implant described in claim any one of 1-5, it is characterised in that including：
Collagen is dispersed in phosphoric acid physiological buffer, and adds additive；
Then carry out emulsifying processing and obtain implant.
7. preparation method according to claim 6, it is characterised in that the collagen is obtained using microbe fermentation method
The recombination human source collagen obtained.
8. the preparation method according to claim 6 or 7, it is characterised in that delay collagen is dispersed in into phosphoric acid physiology
Before in fliud flushing, first the collagen is handled as follows：
The collagen is added in crosslinking agent and carries out crosslinking Treatment, crosslinking agent and the modified collagen egg to obtaining then is removed
Washed in vain.
9. preparation method according to claim 8, it is characterised in that the crosslinking agent is BDO 2-glycidyl
Ether, glutaraldehyde, Geniposide or carbodiimides；The concentration of the crosslinking agent is 0.05-0.5mol/L.
10. preparation method according to claim 8 or claim 9, it is characterised in that the crosslinking agent and the collagen according to
5-10:1 is reacted.
11. the preparation method according to claim any one of 8-10, it is characterised in that the treatment temperature of the crosslinking Treatment
It it is 18-28 DEG C, processing time is 6-20 hours.
12. the preparation method according to claim any one of 8-11, it is characterised in that the washing is to use purified water or phosphorus
Sour physiological buffer is cleaned 3-5 times, each 10-15 minutes.
13. the preparation method according to claim any one of 6-11, it is characterised in that after emulsifying processing, enter
One step includes：Implant is filling in pre-encapsulated injector, then sterilizing, for disposable.
14. preparation method according to claim 13, it is characterised in that the sterilizing uses Co 60 with 15-30kGy
Irradiation dose carries out irradiation sterilization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710383159.XA CN107213028A (en) | 2017-05-26 | 2017-05-26 | A kind of collagen implant and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710383159.XA CN107213028A (en) | 2017-05-26 | 2017-05-26 | A kind of collagen implant and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107213028A true CN107213028A (en) | 2017-09-29 |
Family
ID=59944612
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710383159.XA Pending CN107213028A (en) | 2017-05-26 | 2017-05-26 | A kind of collagen implant and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107213028A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823699A (en) * | 2017-11-17 | 2018-03-23 | 陕西慧康生物科技有限责任公司 | Bleeding stopping and adherence preventing film and preparation method thereof |
| CN113384748A (en) * | 2021-04-29 | 2021-09-14 | 尚诚怡美(成都)生物科技有限公司 | Collagen dermal implant and preparation method thereof |
| CN113768815A (en) * | 2021-09-13 | 2021-12-10 | 浙江崇山生物制品有限公司 | Collagen implant and preparation method thereof |
| CN114146223A (en) * | 2021-12-10 | 2022-03-08 | 三亚悦美科技有限公司 | Recombinant collagen compound injection and preparation method thereof |
| CN114848527A (en) * | 2022-06-02 | 2022-08-05 | 浙江珂瑞康生物医疗科技有限公司 | Collagen composite solution for injection and preparation method thereof |
| CN115317668A (en) * | 2022-08-19 | 2022-11-11 | 江苏东方妍美生物技术发展有限公司 | Long-acting particle type I collagen implant |
| CN115350328A (en) * | 2022-08-19 | 2022-11-18 | 江苏西宏生物医药有限公司 | Long-acting particle III type collagen implant |
| WO2023125686A1 (en) * | 2021-12-28 | 2023-07-06 | Shanghai Qisheng Biological Preparation Co., Ltd. | Soft tissue augmentation using injectable, neutral ph soluble collagen-glycosaminoglycan compositions |
| LU501530B1 (en) * | 2022-02-21 | 2023-08-21 | Ju Li | A method for preparing and implanting collagen |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102229705A (en) * | 2011-06-02 | 2011-11-02 | 陕西巨子生物技术有限公司 | Collagen temperature-sensitive hydrogel and preparation method thereof |
| CN103333508A (en) * | 2013-06-28 | 2013-10-02 | 陕西巨子生物技术有限公司 | Collagen hydrogel for injection and preparation method thereof |
| CN104055795A (en) * | 2013-03-06 | 2014-09-24 | 陕西瑞盛生物科技有限公司 | Injectable implant and preparation method thereof |
| CN105031726A (en) * | 2015-09-02 | 2015-11-11 | 长春博泰医药生物技术有限责任公司 | Medical collagen filling agent |
-
2017
- 2017-05-26 CN CN201710383159.XA patent/CN107213028A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102229705A (en) * | 2011-06-02 | 2011-11-02 | 陕西巨子生物技术有限公司 | Collagen temperature-sensitive hydrogel and preparation method thereof |
| CN104055795A (en) * | 2013-03-06 | 2014-09-24 | 陕西瑞盛生物科技有限公司 | Injectable implant and preparation method thereof |
| CN103333508A (en) * | 2013-06-28 | 2013-10-02 | 陕西巨子生物技术有限公司 | Collagen hydrogel for injection and preparation method thereof |
| CN105031726A (en) * | 2015-09-02 | 2015-11-11 | 长春博泰医药生物技术有限责任公司 | Medical collagen filling agent |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823699A (en) * | 2017-11-17 | 2018-03-23 | 陕西慧康生物科技有限责任公司 | Bleeding stopping and adherence preventing film and preparation method thereof |
| CN113384748A (en) * | 2021-04-29 | 2021-09-14 | 尚诚怡美(成都)生物科技有限公司 | Collagen dermal implant and preparation method thereof |
| CN113384748B (en) * | 2021-04-29 | 2022-04-26 | 尚诚怡美(成都)生物科技有限公司 | Collagen dermal implant and preparation method thereof |
| CN113768815A (en) * | 2021-09-13 | 2021-12-10 | 浙江崇山生物制品有限公司 | Collagen implant and preparation method thereof |
| CN113768815B (en) * | 2021-09-13 | 2022-08-09 | 浙江崇山生物制品有限公司 | Collagen implant and preparation method thereof |
| CN114146223A (en) * | 2021-12-10 | 2022-03-08 | 三亚悦美科技有限公司 | Recombinant collagen compound injection and preparation method thereof |
| WO2023125686A1 (en) * | 2021-12-28 | 2023-07-06 | Shanghai Qisheng Biological Preparation Co., Ltd. | Soft tissue augmentation using injectable, neutral ph soluble collagen-glycosaminoglycan compositions |
| LU501530B1 (en) * | 2022-02-21 | 2023-08-21 | Ju Li | A method for preparing and implanting collagen |
| CN114848527A (en) * | 2022-06-02 | 2022-08-05 | 浙江珂瑞康生物医疗科技有限公司 | Collagen composite solution for injection and preparation method thereof |
| CN115317668A (en) * | 2022-08-19 | 2022-11-11 | 江苏东方妍美生物技术发展有限公司 | Long-acting particle type I collagen implant |
| CN115350328A (en) * | 2022-08-19 | 2022-11-18 | 江苏西宏生物医药有限公司 | Long-acting particle III type collagen implant |
| CN115317668B (en) * | 2022-08-19 | 2023-12-29 | 北京西宏润美医药科技有限公司 | Long-acting microparticle type I collagen implant |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107213028A (en) | A kind of collagen implant and preparation method thereof | |
| JP5735965B2 (en) | Injectable composition combining filler and fibroblast growth medium | |
| Duranti et al. | Injectable hyaluronic acid gel for soft tissue augmentation: A clinical and histological study | |
| EP1734894B1 (en) | Particles for soft tissue augmentation | |
| JP6491199B2 (en) | Hyaluronic acid cross-linking method; injection hydrogel preparation method; resulting hydrogel; use of the resulting hydrogel | |
| CN104055795B (en) | A kind of injectable implant and preparation method thereof | |
| RU2648450C2 (en) | Acceptable for injections sterile water composition on the basis of stitched hyaluronic acid and hydroxyapatite for application in plastic surgery | |
| CN106902381A (en) | Recombination human source collagen stoste, dressing and their preparation method | |
| CN106176292A (en) | A kind of biodegradable injection molding process decorative material and preparation method thereof | |
| CN103179875A (en) | Cosmetic bio-cellulose mask pack sheet and method for manufacturing same | |
| CN111110623A (en) | Self-repairing small needle nutrient solution formula | |
| CN104546639B (en) | A kind of stem cell essence and preparation method thereof | |
| CN103071191A (en) | Preparation method of autologous platelet-factor-rich plasma (PFRP) preparation | |
| CN107998437B (en) | Nano cross-linked sodium hyaluronate gel and preparation method and application thereof | |
| CN110003360A (en) | The method for being used to prepare the hyaluronic acid product of crosslinking | |
| CN104117096A (en) | Novel composite biological dura mater | |
| CN106492276B (en) | A kind of injectable beauty and shaping material and preparation method thereof | |
| CN107929091A (en) | A kind of extracting method of high activity collagen and its application | |
| CN114146223A (en) | Recombinant collagen compound injection and preparation method thereof | |
| CN110327488A (en) | A kind of injection fillers microball preparation and preparation method thereof | |
| CN114099772A (en) | Material for facial shaping and filling and preparation method thereof | |
| CN106474569B (en) | A kind of preparation method of the critical hydrogel of carboxymethyl chitin | |
| CN114159341B (en) | Freeze-dried eye patch and preparation method thereof | |
| Hirsch et al. | Soft tissue augmentation | |
| CN114917403A (en) | Mussel-like mucin gel as well as preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170929 |