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CN113082289A - Composite preparation containing autologous collagen and application thereof - Google Patents

Composite preparation containing autologous collagen and application thereof Download PDF

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Publication number
CN113082289A
CN113082289A CN202110495488.XA CN202110495488A CN113082289A CN 113082289 A CN113082289 A CN 113082289A CN 202110495488 A CN202110495488 A CN 202110495488A CN 113082289 A CN113082289 A CN 113082289A
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autologous collagen
collagen
composite preparation
preparation
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白晋
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24Collagen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/12Phosphorus-containing materials, e.g. apatite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Biophysics (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The invention discloses a composite preparation containing autologous collagen, which comprises calcium hydroxyapatite and autologous collagen. The invention also discloses application of the composite preparation containing the autologous collagen. The composite preparation of the embodiment of the invention is injected into a body, autologous collagen is degraded and absorbed, meanwhile, fibroblast proliferation of the composite preparation can be stimulated, hydroxyapatite calcium is used as a bracket for fibroblast ingrowth to generate new collagen tissues, and the composite preparation of the embodiment of the invention has good biocompatibility, good stability, no wandering property, capability of keeping fixed volume and flexibility, difficult deformation under external force, ideal appearance and hardness of transplanted tissues and lasting nose augmentation effect.

Description

Composite preparation containing autologous collagen and application thereof
The application is a divisional application with application date of 2018, 08 and 27, application number of 201810978561.7, and invention name of 'a composite preparation containing autologous collagen and application thereof'.
Technical Field
The invention relates to the technical field of shaping and beautifying materials, in particular to a composite preparation containing autologous collagen and application thereof.
Background
With the improvement of social and economic levels and the rapid development of the major cosmetic and plastic professions, the beauty-seeking people have more and more demands on facial beauty. The nose is positioned in the center of the face of a person and is called as the soul of five sense organs, the outline and the stereoscopic impression of the face are directly influenced, the appearance of the nose of an Asian person is lower and flat compared with that of a western person, the nose is more round and blunt, and the nose shaping is carried out in order to have a straight nose. The nose augmentation operation is an operation for reshaping or improving the appearance of the nose, and is suitable for beauty seeking patients with low and flat nasal root or nasal back, round and flat nose, large nostrils, wide nasal base and the like, and patients with nasal collapse, nasal sadness, asymmetric nostrils or cleft lip and palate and the like.
The nose humping mode comprises operation and injection nose humping. The injection nose humping is to inject the filler into the subcutaneous part of the nose, so that the appearance of the skin nose humps and is beautiful, and the injection nose humping is favored by broad medical professionals and beauty lovers due to the advantages of convenient and fast method, no anesthesia, no need of opening a knife, easy shaping, repeatability, follow-up treatment and the like. With the demand for injection humps greatly increasing, more and more types of injection filling materials are used.
Currently, the mainstream augmentation nasal filling materials comprise silica gel, polytetrafluoroethylene, hyaluronic acid and autologous cartilage. Wherein: the silica gel has the advantages of high and low temperature resistance, good chemical stability, corrosion resistance and histocompatibility, no toxicity, no carcinogenesis and no distortion, but has the defects of unfixed property, easy sliding displacement and poor plasticity. Polytetrafluoroethylene is a soft graft material with a micropore structure, has better tissue compatibility than silicone rubber, is easy to shape, has softer material than silicone rubber, has smoother transition between prosthesis and surrounding tissues, has more natural appearance of a nose after operation, is an ideal material for humping the nose and improving the shape of the nose tip part, but has high price, and influences the popularization and the use of the material. Hyaluronic acid is a substance naturally existing in tissues, is one of components of human dermal tissues, has the advantages of safe materials, instant effect, short time and almost no recovery period after operation, but can be slowly absorbed, generally the hyaluronic acid nasal augmentation can be maintained for about 6-12 months, and repeated injection is needed. The autologous cartilage is mostly taken from costal cartilage, nasal septum cartilage and auricular cartilage, has the advantages of no rejection and strong anti-infection capability, and simultaneously has the defects of residual incision scars at the taking-out position of the material and partial absorption.
In view of this, the present disclosure is set forth.
Disclosure of Invention
In order to solve the problems of the prior art, the embodiments of the present invention are directed to providing a complex formulation comprising autologous collagen and applications thereof.
To achieve the above objects, a first aspect of embodiments of the present invention provides a complex formulation comprising autologous collagen, the complex formulation comprising calcium hydroxyapatite and autologous collagen.
Further, the particle size of the calcium hydroxyapatite is 25-45 μm.
Further, the preparation method of the autologous collagen comprises the following steps: blood is collected by a human body through blood collection, the blood enters a whole blood separator after being centrifuged for the first time, secondary centrifugation is carried out in the whole blood separator, the whole blood centrifugation is divided into three layers, a plasma layer, a white membrane layer and a red blood cell layer are sequentially arranged from top to bottom, liquid of the plasma layer, the white membrane layer and the red blood cell layer is respectively led into different storage units through catheters to be separately stored, a proper amount of plasma layer and white membrane layer liquid are taken out from the storage units to be mixed in proportion, preliminary purification is carried out through a chromatography unit, and the required autologous collagen is obtained through further purification of a diafiltration unit.
Further, the preparation method of the compound preparation comprises the following steps: adding hydroxyapatite calcium and autologous collagen into the binder, and uniformly dispersing by ultrasonic waves.
Furthermore, 0.01-0.02g of calcium hydroxyapatite and 0.02-0.06g of autologous collagen are added into each 10ml of the adhesive.
Further, the binder comprises sodium carboxymethylcellulose, mannitol and physiological saline in a weight ratio of 1: (1-3): (5-10)
A second aspect of embodiments of the present invention provides a use of the above-described complex formulation comprising autologous collagen for the preparation of a filling material for augmentation rhinoplasty.
The hydroxyapatite calcium is a polymer material containing micropores and forming human bones and teeth, has a larger theoretical density of 3.156g/cm < 3 >, a refractive index of 1.64-1.65 and a Mohs hardness of 5, is slightly soluble in water, is weakly alkaline (pH is 7-9), is easily soluble in acid and is hardly soluble in alkali. A large number of biocompatibility tests prove that the calcium hydroxyapatite can be firmly and chemically combined with bone formation, and has the advantages of good histocompatibility, no need of an allergy test and high viscosity.
The autologous collagen is prepared from autologous collagen which is extracted from human venous blood and is rich in a large number of platelets and collagen, the blood is divided into three layers by centrifugation, a plasma layer mainly comprises plasma, water, protein, salts, various ions and the like, a white membrane layer mainly comprises a platelet-rich area, a lymphocyte-rich area, a monocyte-rich area and a granulocyte-rich area, the erythrocyte layer can be simply divided into young erythrocytes and normal erythrocytes, and the mixed liquid of the extracted plasma layer and the white membrane layer contains a large number of collagen and is rich in platelets and various growth factors, so that after entering a superficial dermis, the autologous collagen, elastic fibers, colloid and the like can be stimulated to generate, and tissues can be regenerated.
Sodium carboxymethyl cellulose is a cellulose derivative with good biocompatibility, and the aqueous solution of the sodium carboxymethyl cellulose has certain viscosity, so that the sodium carboxymethyl cellulose can be used as an adhesive of tablets and a suspending agent of injections.
Mannitol, also known as D-mannitol, is an isomer with sorbitol. It is a non-hygroscopic, odorless, white or colorless crystalline powder. Mannitol, as a hexahydric sugar alcohol, has the characteristics of stable property, no need of insulin for physiological metabolism and the like, and also has unique physiological performance. Mannitol is freely filtered from the glomerulus after entering the body, and the renal tubules have a limited reabsorption mechanism for mannitol, are pharmacologically inactive, are poorly metabolized in the human body, and are not easily accessible to the tissues via the capillaries. After mannitol is injected into a body, mannitol molecules can only flow in blood vessels, so that osmotic gradient is generated between tissues and an intravascular system, liquid is promoted to flow from the tissues to the blood vessels, the osmotic pressure of plasma is rapidly increased, excessive water in the tissues is transferred to the plasma, and then the excessive water is discharged out of the body through a renal excretion system, so that the effects of diuresis and drainage are achieved.
The embodiment of the invention has the following advantages:
according to the embodiment of the invention, calcium hydroxyapatite and autologous collagen are used as filling components of the nose augmentation material, a mixture containing sodium carboxymethylcellulose, mannitol and normal saline is used as a dispersion carrier, the filling components can be stably dispersed in the dispersion carrier for a long time, and the nose augmentation material is convenient to inject, and has the characteristics of moderate degradation time, complete absorption of degradation products, no residue in a human body and high application safety.
The composite preparation provided by the embodiment of the invention is injected into a body, autologous collagen is degraded and absorbed along with the lapse of time, meanwhile, autologous collagen can stimulate the proliferation of fibroblasts, hydroxyapatite calcium is used as a scaffold for the inward growth of the fibroblasts to generate new collagen tissues in situ, and the composite preparation has the advantages of ideal tissue appearance and hardness and lasting nose augmentation effect.
The composite preparation has excellent biocompatibility, no rejection reaction and anaphylactic reaction after being applied to a human body, and is safer and more effective in application.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
Example 1
The preparation method of the composite preparation containing autologous collagen of the embodiment comprises the following steps: adding 0.012g of calcium hydroxyapatite with particle size of 40 μm and 0.04g of autologous collagen into 10ml of sodium acrylate, and uniformly dispersing by ultrasonic wave.
Wherein, the binder comprises sodium carboxymethylcellulose, mannitol and physiological saline, and the weight ratio of the sodium carboxymethylcellulose to the mannitol to the physiological saline is 1: 2: 6.
the preparation method of the autologous collagen comprises the following steps: blood is collected by a human body through blood collection, the blood enters a whole blood separator after being centrifuged for the first time, secondary centrifugation is carried out in the whole blood separator, the whole blood centrifugation is divided into three layers, namely a plasma layer, a white membrane layer and a red blood cell layer from top to bottom, the liquids of the plasma layer, the white membrane layer and the red blood cell layer are respectively led into different storage units through guide tubes to be stored separately, a proper amount of the liquids of the plasma layer and the white membrane layer are taken out from the storage units to be mixed according to the ratio of 1:1, and the liquids are subjected to primary purification through a chromatography unit and further purified through a diafiltration unit to obtain the required autologous collagen.
Example 2
The preparation method of the composite preparation containing autologous collagen of the embodiment comprises the following steps: adding 0.015g of hydroxyapatite calcium with the particle size of 25 mu m and 0.036g of autologous collagen into 10ml of sodium acrylate, and uniformly dispersing by ultrasonic waves.
Wherein, the binder comprises sodium carboxymethylcellulose, mannitol and physiological saline, and the weight ratio of the sodium carboxymethylcellulose to the mannitol to the physiological saline is 1: 3: 8.
the preparation method of the autologous collagen comprises the following steps: blood is collected by a human body through blood collection, the blood enters a whole blood separator after being centrifuged for the first time, secondary centrifugation is carried out in the whole blood separator, the whole blood centrifugation is divided into three layers, namely a plasma layer, a white membrane layer and a red blood cell layer from top to bottom, the liquids of the plasma layer, the white membrane layer and the red blood cell layer are respectively led into different storage units through guide tubes to be stored separately, a proper amount of the liquids of the plasma layer and the white membrane layer are taken out from the storage units to be mixed according to the ratio of 1:1, and the liquids are subjected to primary purification through a chromatography unit and further purified through a diafiltration unit to obtain the required autologous collagen.
Example 3
The preparation method of the composite preparation containing autologous collagen of the embodiment comprises the following steps: adding 0.01g of calcium hydroxyapatite with the particle size of 35 mu m and 0.06g of autologous collagen into 10ml of sodium acrylate, and uniformly dispersing by ultrasonic waves.
Wherein, the binder comprises sodium carboxymethylcellulose, mannitol and physiological saline, and the weight ratio of the sodium carboxymethylcellulose to the mannitol to the physiological saline is 1: 2: 7.
the preparation method of the autologous collagen comprises the following steps: blood is collected by a human body through blood collection, the blood enters a whole blood separator after being centrifuged for the first time, secondary centrifugation is carried out in the whole blood separator, the whole blood centrifugation is divided into three layers, namely a plasma layer, a white membrane layer and a red blood cell layer from top to bottom, the liquids of the plasma layer, the white membrane layer and the red blood cell layer are respectively led into different storage units through guide tubes to be stored separately, a proper amount of the liquids of the plasma layer and the white membrane layer are taken out from the storage units to be mixed according to the ratio of 1:1, and the liquids are subjected to primary purification through a chromatography unit and further purified through a diafiltration unit to obtain the required autologous collagen.
Example 4
The preparation method of the composite preparation containing autologous collagen of the embodiment comprises the following steps: adding 0.02g of hydroxyapatite calcium with the particle size of 45 mu m and 0.02g of autologous collagen into 10ml of sodium acrylate, and uniformly dispersing by ultrasonic waves.
Wherein, the binder comprises sodium carboxymethylcellulose, mannitol and physiological saline, and the weight ratio of the sodium carboxymethylcellulose to the mannitol to the physiological saline is 1: 3: 10.
the preparation method of the autologous collagen comprises the following steps: blood sampling is carried out to the human body through the blood sampling, and blood gets into the whole blood separator after centrifugation for the first time to carry out the secondary centrifugation in the whole blood separator, the whole blood centrifugation divide into the three-layer, and top-down is plasma layer, leucoderma layer and red blood cell layer in proper order, and the liquid with plasma layer, leucoderma layer and red blood cell layer is separately deposited through the different storage unit of pipe introduction respectively, takes out proper amount plasma layer and leucoderma layer liquid by the storage unit and according to 1:1, mixing, performing primary purification by a chromatography unit, and further purifying by a diafiltration unit to obtain the required autologous collagen.
Example 5
The preparation method of the composite preparation containing autologous collagen of the embodiment comprises the following steps: adding 0.011g of calcium hydroxyapatite with the particle size of 30 mu m and 0.05g of autologous collagen into 10ml of sodium acrylate, and uniformly dispersing by ultrasonic waves.
Wherein, the binder comprises sodium carboxymethylcellulose, mannitol and physiological saline, and the weight ratio of the sodium carboxymethylcellulose to the mannitol to the physiological saline is 1: 1: 5.
the preparation method of the autologous collagen comprises the following steps: blood sampling is carried out to the human body through the blood sampling, and blood gets into the whole blood separator after centrifugation for the first time to carry out the secondary centrifugation in the whole blood separator, the whole blood centrifugation divide into the three-layer, and top-down is plasma layer, leucoderma layer and red blood cell layer in proper order, and the liquid with plasma layer, leucoderma layer and red blood cell layer is separately deposited through the different storage unit of pipe introduction respectively, takes out proper amount plasma layer and leucoderma layer liquid by the storage unit and according to 1:1, mixing, performing primary purification by a chromatography unit, and further purifying by a diafiltration unit to obtain the required autologous collagen.
Example 6
The preparation method of the composite preparation containing autologous collagen of the embodiment comprises the following steps: adding 0.015g of hydroxyapatite calcium with the particle size of 45 mu m and 0.045g of autologous collagen into 10ml of sodium acrylate, and uniformly dispersing by ultrasonic waves.
Wherein, the binder comprises sodium carboxymethylcellulose, mannitol and physiological saline, and the weight ratio of the sodium carboxymethylcellulose to the mannitol to the physiological saline is 1: 2: 5.
the preparation method of the autologous collagen comprises the following steps: blood sampling is carried out to the human body through the blood sampling, and blood gets into the whole blood separator after centrifugation for the first time to carry out the secondary centrifugation in the whole blood separator, the whole blood centrifugation divide into the three-layer, and top-down is plasma layer, leucoderma layer and red blood cell layer in proper order, and the liquid with plasma layer, leucoderma layer and red blood cell layer is separately deposited through the different storage unit of pipe introduction respectively, takes out proper amount plasma layer and leucoderma layer liquid by the storage unit and according to 1:1, mixing, performing primary purification by a chromatography unit, and further purifying by a diafiltration unit to obtain the required autologous collagen.
Test examples
In order to demonstrate that the complex formulation of the present invention has a good nasal augmentation effect, the present invention conducted the following efficacy test.
1. General data
60 nasal patients who voluntarily receive nose augmentation in the mechanism in 5 months-2017 months in 2015 are selected as study objects, all patients have good health conditions and no other systemic diseases, and informed consent is signed before nose augmentation. Patients were randomized into trial 1-6 groups of 10 cases each, with trial 1 group: male 2 cases, female 8 cases, age 28 ± 8.2 years; test 2 groups: 3 cases in men, 7 cases in women, age 29 ± 7.6 years; run 3 groups: 2 cases in men, 8 cases in women, age 28 ± 7.0 years; run 4 groups: 1 male, 9 female, age 30 ± 6.8 years old; run 5 groups: 4 cases in men, 6 cases in women, age 29 ± 8.0 years; test 6 groups: male 2 cases, female 8 cases, age 27 ± 8.7 years. The patients in each group have no obvious difference in general data such as sex, age and the like, and have no statistical significance (P > 0.05).
2. Method of treatment
The injection hump nose adopts a tunnel injection method, namely, the injection hump nose is pushed while retreating after the needle is inserted, and the needle is pulled out without bringing the injection hump nose to the superficial layer of the dermis; the force is uniform and constant thumb pressure is maintained. Direct injection is required at the correct level of the skin, at 3 different levels, deep dermis, superficial subcutaneous layer and extraperiosteum.
Tests 1-6 the composite preparations prepared in examples 1-6 of the present invention were used for injection at a dose of 2 + -0.5 ml, and were fixed locally for 24 hours after injection.
3. Criteria for therapeutic effect
The effect is shown: after injection, the patient has very satisfactory nasal appearance and positive lateral effect, the nasal part has perfect continuity, and the naked eye has no visible defects.
The method has the following advantages: after injection, the shape of the nose is changed, such as the nasal root is raised, the nasal tip is rounded, but the defects of visual inspection, such as the misnormal axis of the middle nose and the discontinuous nasal line, still exist.
And (4) invalidation: the appearance of the nose is not changed before and after injection, and complications such as infection bleeding and the like appear after operation.
4. Results
After injection, at follow-up 12 months, the results of the treatment effect of the test groups 1-6 are shown in Table 1.
TABLE 1
Group of Show effect Is effective Invalidation Total effective rate
Test 1 group 6 4 0 100%
Test 2 groups 5 4 1 90%
Test 3 groups 7 3 0 100%
Test 4 groups 5 5 0 100%
Test 5 groups 6 3 1 90%
Test 6 groups 5 4 1 90%
The total effective rate of the test group reaches more than 90 percent, and the composite preparation of the embodiment of the invention has good biocompatibility, good stability, no wandering property, fixed volume and flexibility, difficult deformation under external force, ideal tissue appearance and hardness after transplantation and lasting nose augmentation effect.
Although the invention has been described in detail above with reference to a general description and specific examples, it will be apparent to one skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.

Claims (2)

1. A composite preparation comprising autologous collagen, wherein the composite preparation comprises calcium hydroxyapatite and autologous collagen;
the particle size of the hydroxyapatite calcium is 35 mu m;
the preparation method of the compound preparation comprises the following steps: adding hydroxyapatite calcium and autologous collagen into the binder, and uniformly dispersing by ultrasonic waves;
0.01g of hydroxyapatite calcium and 0.06g of autologous collagen are added into each 10ml of the adhesive;
the binder comprises sodium carboxymethyl cellulose, mannitol and physiological saline, wherein the weight ratio of the sodium carboxymethyl cellulose to the mannitol to the physiological saline is 1: 2: 7;
the preparation method of the autologous collagen comprises the following steps: blood sampling, blood gets into the whole blood separator after centrifugation for the first time to carry out the centrifugation of secondary in the whole blood separator, the whole blood centrifugation divide into the three-layer, and top-down is plasma layer, leucocyte layer and erythrocyte layer in proper order, and the liquid with plasma layer, leucocyte layer and erythrocyte layer is separately deposited through the different storage unit of pipe introduction respectively, takes out proper amount plasma layer and leucocyte layer liquid by the storage unit and according to 1:1, mixing, performing primary purification by a chromatography unit, and further purifying by a diafiltration unit to obtain the required autologous collagen.
2. Use of the complex formulation comprising autologous collagen according to claim 1 for the preparation of a material for nasal augmentation.
CN202110495488.XA 2018-08-27 2018-08-27 Composite preparation containing autologous collagen and application thereof Withdrawn CN113082289A (en)

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CN201810978561.7A CN109078220A (en) 2018-08-27 2018-08-27 A kind of compound formulation comprising autologous collagen albumen and its application
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