CN1935279A - Human soft tissue filler for injection and its preparing method - Google Patents
Human soft tissue filler for injection and its preparing method Download PDFInfo
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- CN1935279A CN1935279A CN 200610152104 CN200610152104A CN1935279A CN 1935279 A CN1935279 A CN 1935279A CN 200610152104 CN200610152104 CN 200610152104 CN 200610152104 A CN200610152104 A CN 200610152104A CN 1935279 A CN1935279 A CN 1935279A
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Abstract
The present invention relates to a human body soft-tissue filling agent. It is mainly formed from cell component and hyaluronic acid. In the filling agent for each milliliter of injection the cell component content is 10000000-50000000 and hyaluronic acid content is 2.0-30 mg. Besides, said invention also provides the preparation method of said human body soft tissue filling agent.
Description
Technical field
The present invention relates to a kind of tissue filling agent and preparation method thereof, more particularly, is a kind of human soft tissue filler for injection and preparation method thereof.
Background technology
The history that human body soft tissue is filled can be traced back to 19th-century.Initial injection is a foreign materials with the packing material that the human body filler adopts, and comprises paraffin and the siloxane solution abandoned because of side effect.Use extrinsic protein subsequently again as packing material, the collagen protein filler of cattle especially, this filler effect that can obtain medical treatment is is at once digested and assimilated but be organized in three to six months.Showed to using the proteic experimenter's investigation of bovine collagen that the effect of a processing procedure generally can only continue the 4-6 month, and anaphylaxis can appear in the extrinsic protein material.
The soft tissue filler that also occurred a kind of FIBREL of being called on the American market, it is the mixture of gelatin powder and glycine and patient's blood plasma, it is effective to the part patient, but is prone to problems such as injection site agglomerate and curative effect be not lasting.
Hyaluronic acid (Haluronic acid, the HA) approval that December obtained U.S. FDA on 12nd in 2003 of U.S. Q-Med Scandivavia company commodity Restyland by name is as the reduce wrinkle injection.Hyaluronic acid is a kind of glucosan aldehydic acid, extensively is present in tissues such as Placenta Hominis, crystalline lens, articular cartilage, dermal layer of the skin, and tissue and cell are played lubricated and nourishing effect, and anabolic body fluid environment is provided simultaneously.Hyaluronic advantage is a natural component, and safety has no side effect, but it is held time and generally has only 6 months.
Above-mentioned material in use directly is filled to desired area, and it has the advantages that to take effect rapidly, but has the safety issue of synthetic material, and the biological extraction material is absorbed by the body gradually and makes the treatment effect short problem of holding time.
Along with the development of tissue engineering technique, autologous tissue's living materials filler has appearred.
Disclose a kind of injection of Wrinkle-and scar-removing among the Chinese patent 03155833.X, used autologous skin,, be made in a kind of injection in the Glucose Liquid, treated cicatrix and dispel wrinkle through in-vitro separation, cultivation and amplification.Because the biomaterial that this technology is used is taken from the patient from body, no rejection, effect is lasting, but the weak point of this technology is, the collagen content that can bring into play the filling of human body soft tissue and repair function in the injection immediately is lower, cause being expelled to and take effect behind cicatrix and the wrinkle place slowlyer, generally take 4-6 month; In addition, use animal serum also may have the problem of safety aspect as the composition of culture fluid.
Autologous tissue's living materials filler is owing to contain the cell that can produce from the body collagen protein, and its effect is more lasting than the non-living body material, generally can reach 5-10, but because collagen protein is excretory gradually by cell, can not take effect immediately after the injection.
Up to now, do not find as yet in the prior art to take effect fast and the persistent human soft tissue filler for injection of curative effect.
Summary of the invention
In order to overcome the deficiency of above-mentioned human soft tissue filler for injection, the object of the present invention is to provide a kind ofly take effect fast, curative effect is lasting, operation receiveing person's satisfaction is higher human soft tissue filler for injection.
Another object of the present invention provides the preparation method of this injection filler.
For achieving the above object, the present invention is by the following technical solutions:
A kind of human soft tissue filler for injection, it mainly is made into by cell component and hyaluronic acid, and the content of cell component is ten thousand of 1000-5000 in every milliliter of injection filler, and hyaluronic content is the 2.0-30 milligram; Described cell component be meant adopt therapist from the skin of body through external low serum or serum-free culture and amplification, collect the corium that obtains and become the fiber stem cell, become at least a in fiber precursor, the fibroblast.
Preferably, in filler of the present invention, described through cultivate with amplification after the corium collected to become the fiber stem cell, become the ratio of fiber precursor, fibroblastic quantity be 10-20: 50-70: 20-30.
Being used for hyaluronic acid of the present invention can the animal derived material of right and wrong, also can be the hyaluronic derivant of extracting from animal tissue, and non-immunogenicity for the pharmaceutical grade product, is generally hyaluronate sodium, but preferred non-animal source hyaluronic acid.
Preferably, in filler of the present invention, hyaluronic content is 3 to 25 mg/ml injection filleies, further preferred 20 mg/ml injection filleies.
Filler of the present invention is except cell component and hyaluronic acid, can also contain some auxiliary elements, described auxiliary element can be this area common can join any or multiple composition in the filler, as from body collagen protein, vitamin, glucose, etc. ooze normal saline or the like.
The low blood serum medium that the present invention uses only need add 3%～5% hyclone, and traditional culture medium must add about 10% hyclone usually, low blood serum medium does not have harmful effect for cell growth, propagation, form, activity and function, even makes moderate progress.
In addition, the present invention also provides a kind of preparation method of described human soft tissue filler for injection, and this method comprises the following steps:
(1) adopts therapist to carry out external low serum or serum-free culture and amplification, resulting corium is become the fiber stem cell, becomes fiber precursor, fibroblast to collect from the skin of body;
(2) cell component and the hyaluronic acid of collecting is made into human soft tissue filler for injection.
The skin histology that the present invention gathered can be behind ear, cuts eye pouch, cut the resulting skin of eyebrow or other position, comprises epidermis and corium simultaneously.
In filler preparation method provided by the present invention, the a small amount of skin of therapist from body will be derived from, for example, the skin of 1-30 square millimeter, in low serum that has added somatomedin and active material or serum-free medium, carry out In vitro culture and amplification, obtain corium and become the fiber stem cell, become fiber precursor, fibroblast.
In described external low serum or serum-free culture and the amplification, the composition of described culture fluid can be this area basic culture solution commonly used.Preferably, in external low serum or serum-free culture and amplification procedure, also comprise somatomedin and active material in the culture fluid of use.Described somatomedin is epithelium growth factor, fibroblast growth factor; Described active material is hydrocortisone, heparin.The content of described epithelium growth factor in culture fluid can be preferably 3 nanograms/milliliter for 1 to 5 nanograms/milliliter; The content of described fibroblast growth factor in culture fluid can be preferably 10 nanograms/milliliter for 2 to 20 nanograms/milliliter; The content of described hydrocortisone in culture fluid can be preferably 1 mcg/ml for 0.2 to 2 mcg/ml; The content of described heparin in culture fluid can be preferably 10 mcg/ml for 2 to 20 mcg/ml.Above-mentioned culture fluid and somatomedin and active material can be the commercially available prod that is selected from a company or a plurality of company (as the Cascade company of the U.S., Sigma company, Hyclne company etc.).
In filler preparation method provided by the present invention, described In vitro culture and amplification can be adopted common any In vitro culture and the amplification method that obtains autogenous cell that be used in this area, as tissue digestion culture method, tissue mass cell culture etc., preferably adopt tissue mass cell culture.
Further describe filler preparation method provided by the present invention below, but therefore the present invention is not subjected to any restriction.
1, autologous skin is drawn materials
Disinfect the position of drawing materials in alcohol, carry out local surfaces anesthesia.Take off with cutisector or scalpel and surgical scissors epidermis and dermal tissue, put into tissue and preserve liquid the 1-30 square millimeter.Wound site is made one to three pin sew up, adhesive bandage covers.Also can adopt the unnecessary skin histology piece of facial plasty when operation excision, as the excision eye pouch or cut the resulting skin of eyebrow.
2, skin histology is cultivated pre-treatment
The skin histology piece is positioned in the culture dish cleans the epithelium position, remove subcutaneous tissue and fat then, skin histology is shredded skin chips into the 0.1-0.5 square millimeter, at last skin chips is tiled in the bottom surface of culture dish.In addition, for cut eye pouch by doing, cut that eyebrow operation or other position obtain greater than 4 square millimeters skin histology, can at first the skin histology piece be digested a period of time with trypsin solution, more postdigestive piece of tissue is shredded the bottom surface that is tiled in culture dish.
3, cells in vitro is cultivated
Comprise two steps of primitive cell culture and passage cell cultivation.
Former be commissioned to train foster: in the culture dish of the skin chips that tiles, add DMEM (Dulbecco ' sModified Eagle ' s Medium) and low serum or serum-free medium and cultivate, make the cell amplification cultivation of can going down to posterity to the culture dish bottom surface of 50%-90%.
The cultivation of going down to posterity: on the former foster basis of being commissioned to train, add somatomedin (as epithelium growth factor, fibroblast growth factor etc.) and active material (as hydrocortisone, heparin etc.), cultivate 2-8 week, approximately cultivate and be expanded to 15,000,000-200,000,000 cells.
The content of epithelium growth factor in culture fluid can be preferably 3 nanograms/milliliter for 1 to 5 nanograms/milliliter; The content of described fibroblast growth factor in culture fluid can be preferably 10 nanograms/milliliter for 2 to 20 nanograms/milliliter; The content of described hydrocortisone in culture fluid can be preferably 1 mcg/ml for 0.2 to 2 mcg/ml; The content of described heparin in culture fluid can be preferably 10 mcg/ml for 2 to 20 mcg/ml.
Adopt this area cell culture condition commonly used get final product, as can being 37 ℃ with above-mentioned low serum or serum-free medium in temperature with the hypodermal cell (containing into fiber stem cell, one-tenth fiber precursor and fibroblast) of turning out from piece of tissue, 5% CO
2Cultivate in the cell culture incubator, changed in every 3-4 days and to state culture fluid once, until the content that obtains required cell component.
4, filler preparation
To cultivate quantity and meet the requirements of cell and at first use trypsin to carry out digestion process, and make it break away from the culture dish bottom surface, clean for several times the removal exogenous growth factor and active substance at the DMEM that uses no extrinsic protein.Directly add in hyaluronic acid with a small amount of collagen protein the cell of collecting again, mixing, be made into the injection filler, perhaps with the cell collected with contain other suitable compositions such as glucose, vitamin and add hyaluronic acid again after mixed, total number of cell component is ten thousand of 1000-5000 in every milliliter of injection filler, and hyaluronic content is 2.0-30mg/ml.Described process for preparation can adopt this area conventional method, as under aseptic condition, hyaluronic acid is dissolved in the Cell sap.
Compared with prior art, human soft tissue filler for injection of the present invention has comprised a large amount of hyaluronic acids, produces fast at the injection part potential energy and fills reduce wrinkle and repairing effect; Subsequently, the cell component that contains in the injection filler can constantly secrete collagen protein, keeps the effect of filling and repairing.This human soft tissue filler for injection obvious filling and repairing effect can occur fast after injection, and curative effect is lasting.In addition, human soft tissue filler for injection of the present invention has used low serum or serum-free culture in preparation process, and exogenous immunogenic substance content is extremely low, greatly reduces injection postoperative infection zoonosis and danger hypersensitive takes place.And because the hyaluronic acid pair cell plays lubricated and the nourishing effect, but inducing cell generate collagen fabric and make tissue regeneration, make reduce wrinkle and repairing effect more natural.
Therefore, human soft tissue filler for injection of the present invention can be widely used in beauty treatment, improve in the filling and reparation of skin elasticity and gloss and other position and type, comprise and handle the various symptoms that cause owing to corium is damaged, for example facial wrinkles, depressed scar, striae gravidarum, the back of the hand wrinkle etc. also can be used for rich lip, strengthen dermis thickness and improve dermal matrix etc.
Description of drawings
Fig. 1 cultivates successful hypodermal cell morphology photo under 100 times of optical microscopes;
Fig. 2 is human soft tissue filler for injection morphology photo under 100 times of optical microscopes of a specific embodiment of the present invention;
Fig. 3 and Fig. 4 are the contrast photos before and after the specific embodiment treatment forehead stricture of vagina of the present invention;
Fig. 5 and Fig. 6 are that a specific embodiment of the present invention is treated the contrast photo of stricture of vagina front and back near the eyes;
Fig. 7 and Fig. 8 are the contrast photos before and after the specific embodiment treatment glabella stricture of vagina of the present invention;
Fig. 9 and Figure 10 are the contrast photos before and after the specific embodiment treatment depressed scar of the present invention;
Figure 11 and Figure 12 are the contrast photos before and after the specific embodiment treatment nasolabial fold of the present invention.
The specific embodiment
Further describe human soft tissue filler for injection provided by the present invention and preparation method thereof below, but therefore the present invention is not subjected to any restriction.
Embodiment 1: the preparation of human soft tissue filler
One. from the extraction of body healthy skin sample
Behind 70% alcohol disinfecting ear, use then 10% lignocaine and 100,000/ epinephrine carry out local surfaces anesthesia.With cutisector or scalpel and surgical scissors with the curer ear after 4 square millimeters epidermis and dermal tissue take off, put into tissue and preserve in the liquid (the DMEM cell-preservation liquid is available from U.S. Hyclone company), wound site is made a pin sews up, adhesive bandage covers.
Two. the preparation of cell suspension
1. skin histology is cultivated pre-treatment: the skin histology piece is positioned over cleans the epithelium position in the culture dish, remove subcutaneous tissue and fat then, skin histology is shredded skin chips into the 0.1-0.5 square millimeter, at last skin chips is tiled in the bottom surface of culture dish.
2. primitive cell culture: in the culture dish of the skin chips that tiles, add the hyclone of DMEM and 3%, put into Forma CO
2In the 3131 type incubators, at 37 ℃, 5%CO
2Condition under cultivate, changed every 2～3 days and state culture fluid once, go down to posterity after compiling when primary cell reaches 80%.
3. passage cell is cultivated: adding epithelium growth factor on the former foster basis of being commissioned to train is 3 nanograms/milliliter, fibroblast growth factor 10 nanograms/milliliter, hydrocortisone 1 mcg/ml, heparin 10 mcg/ml, changed in every 3-4 days and state culture fluid once, cultivated for 4 weeks, approximately cultivate and be expanded to 1,500 ten thousand cells.
4. preparation injection: will cultivate quantity and meet the requirements of cell and at first use trypsin to carry out digestion process, and make it break away from the culture dish bottom surface, and re-use the DMEM cleaning 3 times of no extrinsic protein.Cell and a small amount of collagen protein collected are directly added in the hyaluronic acid, and mixing is made into 1ml injection filler, and total number of cell component is 1,000 ten thousand in this injection filler, and hyaluronic content is 20mg/ml.Hyaluronic acid is available from U.S. Q-Med Scandivavia company, and commodity are called Restyland.
Virus detects: after skin histology cultivated for 4 weeks, get the culture fluid that 1ml contains cell and carry out the check of HIV and hepatitis virus, determine that this is virus-free cell.
The immunoreation test: the 4th week was carried out skin test (with penicillin skin test method), no immunoreation with the 0.1ml cell suspending liquid to the operation receiveing person.
Finished product detection:
1) outward appearance: this product is the pale suspension.
2) cell divide calibrating and hyaluronic content in this product:
Become the fiber stem cell: (Huang Hui relies southwest, Wang Zhengguo, Wang Lili, " material is to the effect of epidermal stem cells migration and expression of receptor in the wound healing " to adopt the Brdu TPPA; " Chinese wound magazine " 2004; 20 (3) 142-145.Utilize the nuclear label), 10% one-tenth fiber stem cell is arranged in the product.
Become the fiber precursor: adopt the morphocytology method to observe (do morphological observation under 100 times of optical microscopes, its standard type is tiny long strand), 70% one-tenth fiber precursor is arranged in the product.
Fibroblast: adopt the morphocytology method to observe (do morphological observation under 100 times of optical microscopes, its standard type is to be to touch prominent long rope shape cell) more, 20% fibroblast is arranged in the product.
20 milligrams every milliliter of hyaluronic acids.
3) sterility test: undertaken by " Chinese biological goods rules " (2000 editions) general rule " biological product sterility test rules " A/B item, the result meets aseptic requirement.
Three. treatment
Be used for the forehead wrinkle, canthus fishtail line, neck wrinkle, all wrinkle and tiny wrinkles facial and other body part such as striae gravidarum; Treat 25 examples.
1. check before the therapist art that every index is all normal, comprising: hematuria is routine, electrocardiogram, hepatic and renal function, HIV, HbsAg just.
With the injection site with 70% alcohol disinfecting, the lignocaine anesthesia of local injection 1%.
3. standby in the syringe with 1ml filler suction 1ml.
4. get No. 4.5 long syringe needles of 2.2cm, adopt multiple spot inclined-plane (20 °～45 ° of the angles of syringe needle and skin), when injecting,, it is turned white, make the injection site leave the disperse space during injection injection site epidermis tension injection cell in the injection site.。
The course of treatment: the injection site is injected 2 times altogether, at interval 2 weeks.
Four, clinical follow, nurse:
1. after the operation, apply injection place 2 hours with ice bag.
2. observe the situation of part and whole body: all are normal.
3. secondary oral vitamin C every day (each 200mg, every day is 400mg altogether) took 6 months.
4. postoperative was prevented tanning by the sun and the careful zest cosmetics of using in 3 days
Five, effect is described
Wrinkle disappears substantially in 2 weeks after injection or obviously shoals, and is respond well.Fig. 3 to Fig. 8 is seen in effect contrast before and after the injection.
Embodiment 2: the preparation of human soft tissue filler
One. from the extraction of body healthy skin sample
Behind 70% alcohol disinfecting ear, use then 10% lignocaine and 100,000/ epinephrine carry out local surfaces anesthesia.With cutisector or scalpel and surgical scissors with the curer ear after 4 square millimeters epidermis and dermal tissue take off, put into tissue and preserve in the liquid (DMEM cell-preservation liquid, U.S. Hyclone company), wound site is made two pins sews up, adhesive bandage covers.
Two. the preparation of cell suspension
1. skin histology is cultivated pre-treatment: the skin histology piece is positioned over cleans the epithelium position in the culture dish, remove subcutaneous tissue and fat then, skin histology is shredded skin chips into the 0.1-0.5 square millimeter, at last skin chips is tiled in the bottom surface of culture dish.
2. primitive cell culture: in the culture dish of the skin chips that tiles, add DMEM and serum-free medium, put into Forma CO
2In the 3131 type incubators, at 37 ℃, 5%CO
2Condition under cultivate, changed every 2～3 days and state culture fluid once, go down to posterity after compiling when primary cell reaches 70%.
3. passage cell is cultivated: add epithelium growth factor 4 nanograms/milliliter, fibroblast growth factor 8 nanograms/milliliter, hydrocortisone 0.8 mcg/ml, heparin 8 mcg/ml on the former foster basis of being commissioned to train, cultivate and be expanded to 9,000 ten thousand cells.
4. preparation injection: will cultivate quantity and meet the requirements of cell and at first use trypsin to carry out digestion process, and make it break away from the culture dish bottom surface, and clean 4 times the removal exogenous growth factor and active substance at the DMEM that uses no extrinsic protein.The cell of purification is directly added in the hyaluronic acid, and mixing is made into 3ml injection filler, and total number of cell component is 8,500 ten thousand in this injection filler, and hyaluronic content is 15mg/ml.
Virus detects: after skin histology was cultivated for 4 weeks, get the culture fluid that 1ml contains cell and carry out the check of HIV and hepatitis virus, determine that this is virus-free cell.
The immunoreation test: the 4th week was carried out skin test (with penicillin skin test method), no immunoreation with the 0.1ml cell suspending liquid to the operation receiveing person.
Finished product detection
1) outward appearance: this product is the pale suspension.
Cell divide calibrating and hyaluronic content in this product:
Become the fiber stem cell: adopt the Brdu TPPA to show that 15% one-tenth fiber stem cell is arranged in the effective ingredient of this collection.
Become the fiber precursor: adopt the morphocytology method to observe, 60% one-tenth fiber precursor is arranged in the effective ingredient of this collection.
Fibroblast: adopt the morphocytology method to observe, 25% fibroblast is arranged in the effective ingredient of this collection.
15 milligrams every milliliter of hyaluronic acids.
2) sterility test: undertaken by " Chinese biological goods rules " (2000 editions) general rule " biological product sterility test rules " A/B item, the result meets aseptic requirement.
Three, treatment
Be used for depressed scar after chickenpox, acne, the wound; Treat 15 examples.
1. check before the therapist art that every index is all normal, comprising: hematuria is routine, electrocardiogram, hepatic and renal function, HIV, HbsAg just.
With the injection site with 70% alcohol disinfecting, the lignocaine anesthesia of local injection 1%.
3. standby in the syringe with 3 1ml of 3ml cell suspension suction.
4. injection the time can be selected No. 4 half common syringe needles, along cicatrix major axis far-end inserting needle, peels off under the corium of cicatrix position, can have hemorrhage on a small quantity, treat stopped bleeding after, Cell sap is expelled to intradermal, injection volume is advisable can see that injection site limitation protuberance turns white.
The course of treatment: the injection site is injected 2 times altogether, at interval 2 weeks.
Four, clinical follow, nurse:
1. after the operation, apply injection place 2 hours with ice bag.
2. observe the situation of part and whole body: all are normal.
3. secondary oral vitamin C every day (each 200mg, every day is 400mg altogether) took 6 months.
4. postoperative was prevented tanning by the sun and the careful zest cosmetics of using in one week.
Five, effect is described
Depressed scar obviously shoals in 1 week after injection, and is respond well.Fig. 9 to Figure 10 is seen in effect contrast before and after the injection.
Though describe the present invention in detail with reference to specific embodiments, it is pointed out that these embodiments only are used for understanding better the present invention.It will be apparent to those skilled in that, under situation without departing from the spirit and scope of the present invention, can on basis of the present invention, make some variations and modification.The invention is intended to comprise all such changes and modifications.
Claims (9)
1. human soft tissue filler for injection, this filler mainly is made up of cell component and hyaluronic acid, and the content of cell component is ten thousand of 1000-5000 in every milliliter of this filler, and hyaluronic content is the 2.0-30 mg/ml; Described cell component is meant that the corium that therapist is collected after external low serum or serum-free culture and amplification from the skin of body becomes the fiber stem cell, becomes at least a in fiber precursor, the fibroblast.
2. human soft tissue filler for injection according to claim 1 is characterized in that: described hyaluronic acid is the non-animal source hyaluronic acid, and described hyaluronic content range is 3 to 25 mg/ml injection filleies.
3. human soft tissue filler for injection according to claim 2 is characterized in that: described hyaluronic content is 20 mg/ml injection filleies.
4. according to claim 1 or 3 described human soft tissue filler for injection, it is characterized in that: described through cultivate with amplification after the corium collected to become the fiber stem cell, become the ratio of fiber precursor, fibroblastic quantity be 10-20: 50-70: 20-30.
5. method for preparing any described human soft tissue filler for injection in the claim 1 to 4 may further comprise the steps:
(1) adopts therapist to carry out external low serum or serum-free culture and amplification, collect resulting corium and become the fiber stem cell, become fiber precursor, fibroblast from the skin of body;
(2) cell component and the hyaluronic acid of collecting is mixed with human soft tissue filler for injection; The content of cell component is ten thousand of 1000-5000 in every milliliter of this filler, and hyaluronic content is the 2.0-30 mg/ml.
6. preparation method according to claim 5 is characterized in that: tissue mass cell culture is adopted in described low serum or serum-free In vitro culture and amplification.
7. preparation method according to claim 6 is characterized in that: added somatomedin and active material in described external low serum or serum-free culture and the amplification; Described somatomedin is epithelium growth factor, fibroblast growth factor, and described active material is hydrocortisone, heparin.
8. preparation method according to claim 7 is characterized in that: the content of described epithelium growth factor in culture fluid is 1 to 5 nanograms/milliliter; The content of described fibroblast growth factor in culture fluid is 2 to 20 nanograms/milliliter; The content of described hydrocortisone in culture fluid is 0.2 to 2 mcg/ml; The content of described heparin in culture fluid is 2 to 20 mcg/ml.
9. preparation method according to claim 8 is characterized in that: described epithelium growth factor is 3 nanograms/milliliter in culture fluid; The content of described fibroblast growth factor in culture fluid is 10 nanograms/milliliter; The content of described hydrocortisone in culture fluid is 1 mcg/ml; The content of described heparin in culture fluid is for being 10 mcg/ml.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102625689A (en) * | 2009-05-04 | 2012-08-01 | 尼奥斯泰姆公司 | Method and composition for restoration of age-related tissue loss in the face or selected areas of the body |
| CN106727244A (en) * | 2017-01-10 | 2017-05-31 | 成都中科同体生物医学研究院 | Consubstantiality biological microsphere and the syringe for injecting the microballoon |
| CN113041397A (en) * | 2021-04-08 | 2021-06-29 | 红色未来科技(北京)有限公司 | A facial filler containing crosslinked dextran and its preparation method |
-
2006
- 2006-09-11 CN CN 200610152104 patent/CN1935279A/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102625689A (en) * | 2009-05-04 | 2012-08-01 | 尼奥斯泰姆公司 | Method and composition for restoration of age-related tissue loss in the face or selected areas of the body |
| CN106727244A (en) * | 2017-01-10 | 2017-05-31 | 成都中科同体生物医学研究院 | Consubstantiality biological microsphere and the syringe for injecting the microballoon |
| CN113041397A (en) * | 2021-04-08 | 2021-06-29 | 红色未来科技(北京)有限公司 | A facial filler containing crosslinked dextran and its preparation method |
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