CN110279888A - A kind of injection Ago-Gel agent and preparation method thereof - Google Patents
A kind of injection Ago-Gel agent and preparation method thereof Download PDFInfo
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- CN110279888A CN110279888A CN201910650285.6A CN201910650285A CN110279888A CN 110279888 A CN110279888 A CN 110279888A CN 201910650285 A CN201910650285 A CN 201910650285A CN 110279888 A CN110279888 A CN 110279888A
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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
- A61L27/20—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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Abstract
The present invention relates to a kind of injection Ago-Gel agent and preparation method thereof, belong to medical cosmetology and bio-medical technology field.Injection Ago-Gel agent provided by the invention, it is comprised the following components in parts by weight: 0.5~5 part of agarose, 0.1~1.0 part of hyaluronic acid, 95~100 parts of buffer solution.Gelling agent is prepared using agarose prepared by method of the invention, improves the physical property and syringeability of agarose, in vivo degradable absorption, the duration is long in human body, and sterilized packaging, doctor can be used directly, it is easy to use, quick without secondary dissolution.
Description
Technical field
The invention belongs to medical cosmetologies and bio-medical technology field, and in particular to a kind of injection Ago-Gel agent and
Preparation method.
Background technique
Soft tissue defect is corrected by shaping and beauty technology and repairs the skin of aging shrinkage, keeps the perfection of facial shape
A kind of universal phenomenon is had become with the youth.In various shaping and beauty technologies, injection beautifying technique accounts for the largest percentage, and accounts for about whole
The 40% of a beauty market.Injection beautifying technique is to carry out local modification to human body by way of injection, reaches local form
The beautifying technique that exquisite, configuration is coordinated.The technology has the characteristics that zero restores, is quick and highly-safe, is that beauty needs
The first choice for the person of asking.
Injection beauty is one kind of non-operating shaping beauty, life that can be artificial synthesized by biomaterial using the method for injection
The good Material injection of object compatibility enters skin corium or subcutaneous, is reached by the different mechanism of action and reduces skinfold or moulding
A kind of shaping and beauty method.
The key for injecting beauty is injection material.Material currently used for injecting beauty is broadly divided into absorbable and can not inhale
Two major classes are received, the high molecular material of nonabsorable is mainly polymethyl methacrylate etc., such as " Artecoll " of Holland；It is absorbable
Material mainly has collagen, hyaluronic acid, polylactic acid etc., as " double beauty " injection fillers agent of TaiWan, China, Sweden it is " auspicious
Orchid ", " Sculptra " in the U.S. etc..
Above-mentioned different materials have some defects and need to solve: polymethyl methacrylate can not in human body due to it
It decomposes and cannot be absorbed by tissue, easily form firm fibrocyst in injection site, increase and position movement and thorn occurs
Swash the risk of autoimmune disorder, thus is gradually substituted by absorbable material.
Collagen will not can cause the serious rejection of body, but injection molding process agent as other exogenous implants
Collagen sources in xenogeneic skin, the protein of heterologous can cause allergic reaction in theory, as local skin is red
Spot, swelling, hardening and/or itch etc..It is serious to may occur in which constitutional symptom such as fever, headache, courbature, nausea, malaise
Or there is nettle rash or other fash or various immunity diseases in dizzy, whole body.So pure broken collagen might have
Acute and chronic allergic reaction.And since collagen molecules amount is smaller so that its inject enter human skin after, in some months
Interior to be completely absorbed degradation, curative effect is held time shorter.
Single hyaluronic acid injections are to increase molecular weight by method chemically or physically mostly, clinically
Hyaluronic acid is after entering blood in injection process, it is possible to blood vessel distal be caused to recycle embolism, cutaneous necrosis, retina
The severe complications such as arterial embolism and heart and brain arterial embolism, therefore there is very big safety issue.And without chemically or physically side
The maintenance effect time of the hyaluronic acid that method was crosslinked in vivo is shorter, only 3~4 months or so, it is crosslinked after hyalomitome
Acid is held time also only 6~8 months in vivo, and curative effect is held time short.
The action time of polylactic acid-based product is long, and particles of polylactic acid can stimulate injection site subcutaneous tissue to increase
It is raw, therefore wrinkle effect still can be played after degrading.But existing poly-lactic acid products have hydrophobicity, are unfavorable for protein suction
It receives, and then influences cell adhesion, and be prone to the sedimentation of particles of polylactic acid in clinical manipulation, operation skill is required high.
The use of more " Sculptra " being at present lyophilized preparation, needs solubilizer to be redissolved before use, the process time is long,
48 hours need to be shifted to an earlier date and prepared, be not easy to operate.
104774337 A of Chinese patent CN discloses injection containing the micro-sphere crosslinked hyaluronic acid sodium gel of agar and preparation
Method, using the characteristic of Sodium Hyaluronate and agarose, by Sodium Hyaluronate and agarose microbeads by with 1,2,7,8- bis- rings
Injection cross-linking sodium hyaluronate gel containing agarose microbeads is made after merging in the mode of oxygen octane co-crosslinking.It is well known that
The crosslinking agent has certain bio-toxicity or potential carcinogenicity, although to take stringent control measure true for each manufacturer
The safety of product is protected, but cross-linking sodium hyaluronate gel is to be chronically implanted intracorporal three classes medical instrument, the toxicity of crosslinking agent
It is still factor in need of consideration.
Summary of the invention
The purpose of the present invention is on the basis of existing technology, provide a kind of injection Ago-Gel agent.System of the present invention
Standby injection Ago-Gel agent, it is easy to use, the duration is long, degradable absorption in vivo.
It is a further object of the present invention to provide a kind of preparation methods of above-mentioned injection Ago-Gel agent.
Technical scheme is as follows:
A kind of injection Ago-Gel agent, it is comprised the following components in parts by weight: 0.5~5 part of agarose, non-crosslinked
0.1~1.0 part of bright matter acid, 95~100 parts of buffer solution.
Injection Ago-Gel agent prepared by the present invention, it is comprised the following components in parts by weight: agarose 1.0~4.0
Part, 0.2~0.6 part of non-crosslinked hyaluronic acid, 95~100 parts of buffer solution.
Agarose is extract from Bostrychia montagnei, is a kind of linear polymer, and basic structure is the β-D- of 1,3 connections
Galactolipin and the 3,6- inner ether-L galactolipin of 1,4 connections alternately connect more next long-chain.Agarose is dissolved in hot water, and cooling is made solidifying
Glue.Ago-Gel has preferable biocompatibility, and nodal cell and bodily tissue have good tolerance, will not generate
The reaction of foreign body reaction or immune system.In vivo, agarose is to be removed by the effect of macrophage from application site.
Hyaluronic acid (also known as sodium hyaluronate, abbreviation HA) or its sodium salt are a kind of natural polymer mucopolysaccharide substances, extensively
It is distributed in the connective tissue, cockscomb and streptococcic folder film etc. of mammal, due to not having kind and organspecific, by
Gelling agent made from hyaluronic acid as filler transplant or inject human body all show good human body compatibility, play it is crease-resistant,
Breast augmentation is filled the effects of pad, and without side-effects to human body.
The hyaluronic acid that the present invention uses is preferably non-crosslinked hyaluronic acid, wherein the molecular weight of non-crosslinked hyaluronic acid
It is 500 000~3 000 000, preferably 750 000~2 000 000, more preferably 1 000 000~1 500 000.
The pH for the buffer solution that the present invention refers to is 4.5~7.5；It is preferred that pH is 5.0~7.0.
In a preferred embodiment, the buffer solution that the present invention uses is molten for acetate buffer solution or phosphate-buffered
Liquid.Wherein, phosphate buffer solution is the mixed solution of sodium dihydrogen phosphate, disodium phosphate soln or both.
The acetate buffer solution of above-mentioned submission is selected from the acetate buffer solution that pH is 4.5~7.5；Phosphate-buffered is molten
Liquid, can selected from pH be 4.5~7.5 sodium dihydrogen phosphate, pH be 4.5~7.5 disodium phosphate soln or pH be
4.5~7.5 sodium dihydrogen phosphate and the mixed solution of disodium phosphate soln.
Further, the acetate buffer solution of above-mentioned submission is selected from the acetate buffer solution that pH is 5.0~7.0；Phosphorus
Hydrochlorate buffer solution, can selected from pH be 5.0~7.0 sodium dihydrogen phosphate, pH be 5.0~7.0 disodium hydrogen phosphate it is molten
The mixed solution of sodium dihydrogen phosphate and disodium phosphate soln that liquid or pH are 5.0~7.0.
The present invention also provides the preparation methods of above-mentioned injection Ago-Gel agent, it is mainly comprised the steps that fine jade
Lipolysaccharide, non-crosslinked hyaluronic acid are mixed with buffer solution, after 70~100 DEG C are stirred to react, be down to room temperature to get.
The preparation method of above-mentioned injection Ago-Gel agent, it may include step in further detail below:
(1) prepared by gel: agarose, non-crosslinked hyaluronic acid being mixed with buffer solution, are stirred at 70~100 DEG C
After reaction, it is down to room temperature, prepares gel.
(2) filling: the gel inoculated that step (1) prepares is filled in prefilled syringe；
(3) it sterilizes: being sterilized using gamma-ray irradiation；
(4) it packs: the syringe equipped with gel, syringe needle and the syringe assist handle (boost motor) after sterilizing is filled together
Enter aluminium bag and seal, then uses ethylene oxide sterilizing.
The molecular weight for the non-crosslinked hyaluronic acid that the present invention uses is 500 000~3 000 000, preferably 750 000
~2 000 000, more preferably 1 000 000~1 500 000.
When preparing gel, agarose, non-crosslinked hyaluronic acid are mixed with buffer solution, are stirred at 70~100 DEG C
Reaction, reaction time are 20~90min；Preferably 30~45min.
The pH for the buffer solution that the present invention refers to is 4.5~7.5；It is preferred that pH is 5.0~7.0.
In a preferred embodiment, the buffer solution that the present invention uses is molten for acetate buffer solution or phosphate-buffered
Liquid.Wherein, phosphate buffer solution is the mixed solution of sodium dihydrogen phosphate, disodium phosphate soln or both.
The acetate buffer solution of above-mentioned submission is selected from the acetate buffer solution that pH is 4.5~7.5；Phosphate-buffered is molten
Liquid, can selected from pH be 4.5~7.5 sodium dihydrogen phosphate, pH be 4.5~7.5 disodium phosphate soln or pH be
4.5~7.5 sodium dihydrogen phosphate and the mixed solution of disodium phosphate soln.
Further, the acetate buffer solution of above-mentioned submission is selected from the acetate buffer solution that pH is 5.0~7.0；Phosphorus
Hydrochlorate buffer solution, can selected from pH be 5.0~7.0 sodium dihydrogen phosphate, pH be 5.0~7.0 disodium hydrogen phosphate it is molten
The mixed solution of sodium dihydrogen phosphate and disodium phosphate soln that liquid or pH are 5.0~7.0.
Agarose does not absorb water, and manufactured gel does not also absorb water after being injected in vivo.And hyaluronic acid is hydrophilic, note
It can absorb water from tissue after penetrating.When the present invention prepares gel using agarose, hyaluronic acid is added, improves agarose
Physical property and syringeability, and overall absorption rate is not influenced, the two is complementary to one another, and plays synergistic effect.
Non-crosslinked hyaluronic acid maintains the effect time shorter in vivo, and duration is even in corium or tissue
It does not exceed 4 months.And in the present invention, uncrosslinked hyaluronic acid cooperates with agarose to play one mainly as a kind of auxiliary agent
It the effects of kind hydrophilic, water suction, holds time depending on agarose.Injection Ago-Gel agent prepared by the present invention, in vivo
Maintaining effect to hold time is 8~12 months.
Existing " Sculptra " is lyophilized preparation, needs solubilizer to be redissolved before use, need to shift to an earlier date 48 hours and prepare,
It is not easy to operate.Injection Ago-Gel agent prepared by the present invention, sterilized packaging, doctor can be used directly, without secondary
Dissolution is easy to use, quick.
Compared with 104774337 A of Chinese patent CN, product of the present invention is had the following characteristics that
(1) dosage is different, and main body is different.In 104774337 A of Chinese patent CN, Sodium Hyaluronate dosage be 15~
25mg/ml, agarose dosage are 1~5mg/ml, and main body is Sodium Hyaluronate, that is, the substance to play a major role is hyaluronic acid
Sodium.In the present invention, Sodium Hyaluronate dosage is 1~10mg/ml, and agarose dosage is 5~50mg/ml, is played a major role
For agarose, i.e. main body is agarose.
(2) production technology is different.In 104774337 A of Chinese patent CN, main body is Sodium Hyaluronate, but hyalomitome
Sour sodium degradation in vivo speed is fast, therefore a certain amount of agarose and 1,2,7,8- diepoxyoctane of crosslinking agent is added, will be transparent
Matter acid sodium is crosslinked with agarose, to extend the time of Sodium Hyaluronate in vivo.In the present invention, main body is agar
Sugar, the characteristic and dosage of agarose are the key factor of the degradation time of product of the invention in vivo.Biomaterial agarose
It is metabolized in vivo without native enzyme, there is good persistence；Agarose is slowly inhaled by the effect of macrophage by body
It receives, is eliminated in pentose cycle eventually by interior rete cutaneum.
(3) injection site is different.The crosslinking containing agarose microbeads of the injection of 104774337 A of Chinese patent CN preparation is saturating
Bright matter acid sodium gel, for the filling in plastic and aesthetic surgery for shallow-layer skin.Product of the present invention is deeper injection, such as with note
It penetrates under corium, organized on subcutaneous tissue or bone.For decree line, crow's feet, glabella line, eye rill, puppet line, forehead line,
Plentiful, depth volume filling of nasolabial groove, cheek chin recess, middle deep etc..
Injection Ago-Gel agent prepared by the present invention, has characteristics that
Appearance: tasteless, pale yellow transparent viscous liquid is visible by naked eyes impurity.
Specification: product loading amount is 0.5ml, 1.0ml, 1.5ml, 2.0ml, franchise ± 10%.
PH value: 5.0~7.5.
Shear viscosity: 40000-60000Cp (25 ± 0.2 DEG C, shear rate 10S-1)。
Osmotic pressure: 280~350mOsmol/L.
Protein content: less than 0.1%.
Content of beary metal: less than 10ppm.
It is sterile: sterile.
Bacterial endotoxin: less than 0.1EU/ml.
Hemolytic test: not haemolysis.
Skin irritatin: nothing.
Delayed hypersensitivity reaction: nothing.
Genetoxic: nothing.
Cytotoxicity: it is not more than first order reaction.
Using technical solution of the present invention, advantage is as follows:
Agarose provided by the invention prepares gelling agent, improves the physical property and syringeability of agarose, in vivo
Degradable absorption, the duration is long in human body, and it is 8~12 months that effect, which is held time, is subcutaneously implanted 6 months, fibrous connective
Organize fully wrapped around, filling effect is obvious, surrounding tissue variation without exception.
It is lyophilized preparation, injection Ago-Gel agent prepared by the present invention, through going out relative to existing " Sculptra "
Bacterium bag dress, doctor can be used directly, and be not necessarily to secondary dissolution, easy to use, quick.
Specific embodiment
The following description is intended to explain the principle of the present invention and main feature, not to the raw material group in the present invention
There is specific restriction effect at, ratio.
The molecular weight for the non-crosslinked hyaluronic acid that the present invention uses is 500 000~3 000 000, preferably 750 000
~2 000 000, more preferably 1 000 000~1 500 000.
Embodiment 1
25g agarose and the non-crosslinked hyaluronic acid of 5g (molecular weight ranges 1 000 000~1 500 000) are added
In 1000g phosphate buffer solution (pH 6.8), 80 DEG C are heated to, 30min is stirred, lets cool to room temperature, filling, gamma-rays spoke
According to sterilizing (dosage 25kGy).
Embodiment 2
15g agarose and the non-crosslinked hyaluronic acid of 8g (molecular weight ranges 1 000 000~1 500 000) are added
In 1000g phosphate buffer solution (pH 5.5), 75 DEG C are heated to, 45min is stirred, lets cool to room temperature, filling, gamma-rays spoke
According to sterilizing (dosage 25kGy).
Embodiment 3
By 50g agarose and the non-crosslinked hyaluronic acid of 1g (molecular weight ranges 1 000 000~1 500 000), mixing is equal
It is even, it is added in 1000g phosphate buffer solution (pH 5.0), is heated to 90 DEG C, stir 60min, let cool to room temperature, filling, γ
X ray irradiation x sterilizes (dosage 25kGy).
Embodiment 4
35g agarose and the non-crosslinked hyaluronic acid of 4g (molecular weight ranges 1 000 000~1 500 000) are added
In 1000g phosphate buffer solution (pH 6.0), 85 DEG C are heated to, 45min is stirred, lets cool to room temperature, filling, gamma-rays spoke
According to sterilizing (dosage 25kGy).
Embodiment 5
Heating in 1000g phosphate buffer solution (pH 7.5) is added in 5g agarose and the non-crosslinked hyaluronic acid of 10g
To 80 DEG C, 45min is stirred, is let cool to room temperature, filling, gamma-ray irradiation sterilizes (dosage 25kGy).
Table 1 lists the related test results for the product that embodiment 1-5 is prepared by the method for the present invention.
Comparative example 1
It is slow that 1000g phosphate is added in the non-crosslinked hyaluronic acid of 15g (molecular weight ranges 1 000 000~1 500 000)
(pH 6.8) is rushed in solution, is heated to 80 DEG C, 45min is stirred, lets cool to room temperature, filling, gamma-ray irradiation sterilizing (dosage
25kGy)。
Comparative example 2
It is that 1 200 000 hyaluronic acids are dissolved in 200ml diluted sodium hydroxide solution (1mol/L) by 5g average molecular weight, adds
Enter 2g glycidol ether, stirs to get cross-linked-hyaluronic acid.The cross-linked-hyaluronic acid phosphate buffer solution that pH is 7.4 is soaked
Bubble 3 times, 8 hours every time, stirring was sieved (40 mesh), obtains cross-linked hyaluronic acid gel.It is filling, gamma-ray irradiation sterilizing (dosage
25kGy)。
1 product testing result of table
In conclusion injection Ago-Gel agent disclosed in this invention is easy to use, the duration is long, can drop in vivo
Solution, and using safe, adverse reaction happen that rate is low, and no severe complication happens；Non-carcinogenesis, without hereditary poison
Property, cytotoxicity meets national sector standard to the regulation of bio-medical material no more than I grades.
External degradation test
Test specimen: Examples 1 to 5, comparative example 1 (non-crosslinked hyaluronic acid derivatives) and 2 (cross-linked-hyaluronic acid of comparative example
Gel) obtained by sample.
Test sample 1.5g is weighed, addition has 50mL pH7.4KH2PO4The test tube of 2NaOH buffer, respectively at 37.0 ±
1.0 DEG C of progress Degrading experiments periodically sample.
Have studied influence of the in-vitro simulated Degrading experiment to made sample under the conditions of pH7.4 and 37 ± 1 DEG C.
The results show that comparative example 1 (non-crosslinked hyaluronic acid derivatives) sample starts to degrade, molecular weight after test carries out 2 weeks
It is decreased obviously with initial phase ratio, solution ph reduces.
After test carries out 2 months, under cross-linking hyaluronic acid sodium molecular weight starts in comparative example 2 (cross-linked hyaluronic acid gel)
Drop, solution ph reduce.
After test carries out 2 weeks, the non-crosslinked hyaluronan molecule amount in Examples 1 to 5 sample is begun to decline, but agarose
Microballoon has no significant change.After experiment carries out 8 months, agarose microbeads surface starts small hole occur, under molecular weight starts
Drop, the degradation of agar agarose microbeads is complete at 12 months.
It is subcutaneously implanted effect
Take respectively 1~5 Ago-Gel of the 0.5ml embodiment of the present invention and comparative example 1 (non-crosslinked hyaluronic acid derivatives) and
Comparative example 2 (cross-linked hyaluronic acid gel), is implanted into subcutaneous rat respectively, observation.
After 2 sample injection of Examples 1 to 5 sample, comparative example 1 and comparative example, the reaction such as red, swollen, livid purple is not found.
It being subcutaneously implanted 1 month, for 1 sample implant site of comparative example substantially without filling effect, comparative example 2 has part effect,
Examples 1 to 5 sample filling effect is obvious, surrounding tissue variation without exception.
It is subcutaneously implanted 6 months, Examples 1 to 5 is fully wrapped around by fibrous connective tissue, and filling effect is obvious, surrounding tissue
Variation without exception；2 filling effect of comparative example gradually decreases.
In order to verify the effect (be used as dermal filler) of product of the present invention, following trial test is carried out:
Subject:
40,30~60 one full year of life of age, health, face has obvious decree line, crow's feet, glabella line, eye rill, volume
Head line, lower eyelid recess and other Facial Depression persons etc., male or female.
Test method:
It takes the embodiment of the present invention 1 to prepare resulting product, is injected with 25G needle or 27G syringe needle, injection depth and dosage
Depending on position and degree.By needle in about 30 ° of angle insertion corium deep layer, inclined-plane downward, to reduce to the maximum extent
Implantation material deposits to more superficial face.By applying mild, continuous pressure on plunger rod come injected gel, while slowly taking out
Syringe needle out, thus organizing the formation of single uniform injected gel line.When correcting deeper wrinkle, should be carried out below wrinkle
It is placed in parallel.After the completion of injection, gently massage therapy region, it is ensured that gel is evenly distributed, and gel is moulded into tissue contours.?
After treatment in 24 hours, subject should carry out cold compress using ice bag to treatment region, to reduce rubescent, swelling and stimulation.
Conclusion:
Injection is observed after 48 hours, and in 40 people, 40 people injection sites do not occur the symptoms such as redness, ecchymosis, and no allergy is anti-
It answers.
Injection is observed after 3 months, is had 33 people's wrinkles or recess to completely disappear in 40 people, is reached and fill and lead up effect, accounting
82.5%；There are 5 people's wrinkles or recess to improve obvious, reaches satisfied and fill and lead up effect, but wrinkle or recess naked eyes are still seen, accounting
12.5%；There are 1 people's wrinkle or recess to have a degree of improvement, but improve result and be unsatisfied with, wrinkle or recess are more obvious, account for
Than 2.5%；There are 1 people's wrinkle or recess preceding without significant change, wrinkle or high-visible, the accounting 2.5% that is recessed with injection.
Verified, product of the present invention is safe to the human body effectively, and total effective rate is up to 97.5%.
The above embodiments are merely illustrative of the technical solutions of the present invention, rather than its limitations；Although with reference to the foregoing embodiments
Invention is explained in detail, those skilled in the art should understand that: it still may be to aforementioned each implementation
Technical solution documented by example is modified or equivalent replacement of some of the technical features；And these modification or
Replacement, the range for technical solution of various embodiments of the present invention that it does not separate the essence of the corresponding technical solution.
Claims (10)
1. a kind of injection Ago-Gel agent, which is characterized in that it is comprised the following components in parts by weight: agarose 0.5~5
Part, 0.1~1.0 part of non-crosslinked hyaluronic acid, 95~100 parts of buffer solution.
2. injection Ago-Gel agent according to claim 1, which is characterized in that it includes the group of following parts by weight
Point: 1.0~4.0 parts of agarose, 0.2~0.6 part of non-crosslinked hyaluronic acid, 95~100 parts of buffer solution.
3. injection Ago-Gel agent according to claim 3, which is characterized in that the molecular weight of non-crosslinked hyaluronic acid
It is 500 000~3 000 000, preferably 750 000~2 000 000, more preferably 1 000 000~1 500 000.
4. injection Ago-Gel agent according to claim 1, which is characterized in that the pH of the buffer solution is 4.5
~7.5；It is preferred that pH is 5.0~7.0.
5. injection Ago-Gel agent according to claim 4, which is characterized in that the buffer solution is slow for acetate
Rush solution or phosphate buffer solution.
6. the preparation method of injection Ago-Gel agent described in claim 1, which is characterized in that it mainly includes following step
It is rapid: agarose, non-crosslinked hyaluronic acid are mixed with buffer solution, after 70~100 DEG C are stirred to react, are down to room temperature,
To obtain the final product.
7. the preparation method of injection Ago-Gel agent according to claim 6, which is characterized in that described non-crosslinked
The molecular weight of bright matter acid is 500 000~3 000 000, preferably 750 000~2 000 000, more preferably 1 000 000
~1,500 000.
8. the preparation method of injection Ago-Gel agent according to claim 6, which is characterized in that the buffer solution
PH be 4.5~7.5；It is preferred that pH is 5.0~7.0.
9. the preparation method of injection Ago-Gel agent according to claim 6, which is characterized in that the buffer solution
For acetate buffer solution or phosphate buffer solution.
10. the preparation method of injection Ago-Gel agent according to claim 6, which is characterized in that the reaction time is
20~90min；Preferably 30~45min.
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| CN201910650285.6A CN110279888A (en) | 2019-07-18 | 2019-07-18 | A kind of injection Ago-Gel agent and preparation method thereof |
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| CN201910650285.6A CN110279888A (en) | 2019-07-18 | 2019-07-18 | A kind of injection Ago-Gel agent and preparation method thereof |
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| CN113117143A (en) * | 2020-01-14 | 2021-07-16 | 北京四环制药有限公司 | Application of hyaluronic acid in preparing composition for reducing injection irritation of PLLA |
| CN115414276A (en) * | 2022-06-24 | 2022-12-02 | 辽宁德玛生物科技有限公司 | Agarose gel for injection and its preparing method |
| CN117398518B (en) * | 2023-12-15 | 2024-05-03 | 湘潭格莱威医疗科技有限公司 | Agarose water gel material and application thereof |
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| CN117398518B (en) * | 2023-12-15 | 2024-05-03 | 湘潭格莱威医疗科技有限公司 | Agarose water gel material and application thereof |
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Application publication date: 20190927 |