CN108744054A - A kind of injection-type beauty and shaping facial bulking agent compositions gel and preparation method thereof - Google Patents
A kind of injection-type beauty and shaping facial bulking agent compositions gel and preparation method thereof Download PDFInfo
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- CN108744054A CN108744054A CN201810620176.5A CN201810620176A CN108744054A CN 108744054 A CN108744054 A CN 108744054A CN 201810620176 A CN201810620176 A CN 201810620176A CN 108744054 A CN108744054 A CN 108744054A
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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
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
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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
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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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- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
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Abstract
The invention discloses a kind of injection-type beauty and shaping facial bulking agent compositions gels and preparation method thereof, are used for shaping and beauty.The composition mainly includes the gel and optional particulate such as hydroxyapatite (CaHAP) particulate of non-crosslinked type Sodium Hyaluronate and cellulose ethers organic assembling.The injection-type beauty and shaping is uniform with facial bulking agent compositions quality, it particulate such as hydroxyapatite can be dispersed among gel steadily in the long term, with desired rheological behavior (high elastic modulus and high dynamic viscosity), while being easy to industrial filling and clinical injection.
Description
Technical field
The invention belongs to Cosmetic surgery fields, specifically, being related to a kind of injection-type beauty and shaping face filling
Agent composition gels and preparation method thereof.
Background technology
As Time fleets past, skin meeting nature relaxation and generation wrinkle, especially face contour aging can be aggravated increasingly,
Including visible wrinkle of skin, deep nasolabial groove, line of frowning, puppet line, cheek engagement line, mouth encloses wrinkle, temples collapses.Equally,
Because nasal bridge caused by congenital or wound and brow ridge, lower chin be not proper etc. all to have brought worried pain.It is beautiful
Beautiful is the target of the mankind's eternal topic and pursuit, how effective delay skin aging, beautification appearance be still that people constantly seek
With solve the problems, such as.
By inject the facial filler of beauty and shaping can the effective solution above problem, support the skin collapsed from internal
Skin.In recent years, shaping and beauty can be divided into 2 classes for the material of Soft-tissue operation in the market, and one kind is absorbable material, including but
It is not limited to collagen, hyaluronic acid, hydroxyapatite, l-lactic acid (PLLA)；Another kind of is nonabsorable material, is represented
Substance is silica gel, poly (methyl methacrylate) micro-sphere (PMMA).The product for Soft-tissue operation of U.S. FDA approval listing
In, the use of relatively broad example is at present crystallite porcelainIt includes hydroxyapatite micro-sphere, carboxymethyl fibre
The gel carrier and glycerine of dimension plain (CMC), international monopoly PCT/US2007/017131 also elaborate this.
Crystallite porcelain has high-caliber biocompatibility, and hydroapatite particles can the life of stimulation of endogenous collagen
Production.However the CMC carriers of crystallite porcelain are rapidly absorbed in the living body (in about 3 months), the elimination of collagen new life and CMC
It may not occur simultaneously, therefore cause the potential and of short duration reduction of filling effect.In addition, such as institute in some Science Reports
It states, these filled-type beauty products migrate frequent occurrence, lead to that expected cosmetic result cannot be reached, and there is presently no can
The antidote (reversal agent) of part reparation is carried out to CMC after the application of filler.
Hyaluronic acid is the fabulous bio-medical material of biocompatibility generally acknowledged at present, has been widely used in shaping
Beauty row, side effect is seldom after injection, and long-term complications are rare.In addition, if injection is not good enough, injection hyaluronidase can be passed through
To correct treatment.WO 2014/056723 describes a kind of viscoelastic gel comprising concentration between 1% and 4% (w/v) it
Between hydroxyapatite particle between 10% and 70% (w/v) of cross-linking type sodium hyaluronate and concentration.Cross-linking type hyalomitome
The long-term safety issue of sour residual cross-linker is still troubling, however, the residence time is short in vivo for single hyaluronic acid,
It needs to be injected repeatedly to maintain cosmetic result.
In addition, the above-mentioned injection-type gel containing cross-linking type sodium hyaluronate and particulate such as hydroxyapatite, in industrial production
In face 2 main problems：1) it is to ensure the injection-type gel bubble-free, need to be filling after vacuum outgas, it finds in the process solidifying
Glue is dehydrated, and two-phase section occurs, can not be filling；2) to avoid hydroapatite particles from being deposited at any time in its container, this is solidifying
Glue dynamic viscosity is larger so that extrusion force becomes larger, and is not easy to clinical injection, if reducing viscosity, hydroxyapatite deposition is being injected
Position will appear heterogeneous area.
Invention content
In view of this, the present invention provides a kind of injection-type beauty and shaping facial bulking agent compositions gels and its preparation
Method with excellent biocompatibility, persistence, high moisturizing power, while being kept as the facial filler of beauty and shaping
Desired machinery and the rheological equationm of state, so as to reach desired beauty and shaping effect.
In order to solve the above-mentioned technical problem, the invention discloses a kind of facial bulking agent compositions of injection-type beauty and shaping
Gel, including combined gels matrix and hydroxyapatite particles.
Optionally, the combined gels matrix includes aqueous solution for injection, cellulose ethers or/and Sodium Hyaluronate,
Wherein, cellulose ethers account for the 0.5%-15% of the weight total amount of aqueous solution for injection, and Sodium Hyaluronate accounts for aqueous solution for injection
Weight total amount 0.1%-10%.
Optionally, cellulose ethers account for the 1%-6% of the weight total amount of aqueous solution for injection, and Sodium Hyaluronate accounts for injection
The 0.1%-4% of the weight total amount of aqueous solution.
Optionally, the cellulose ethers are methylcellulose, sodium carboxymethylcellulose, ethyl cellulose, ethoxy
One or several kinds in cellulose, hydroxypropyl cellulose, hypromellose or cyanethyl cellulose.
Optionally, the aqueous solution for injection is that sodium chloride solution that mass concentration is 0.9% or phosphate-buffered are molten
Liquid.
Optionally, the average grain diameter of the hydroxyapatite particles is 5 μm -150 μm；The hydroxyapatite particles account for note
The 10%-70% of the facial bulking agent compositions gel weight total amount of emitting beauty and shaping.
Optionally, the average grain diameter of the hydroxyapatite particles is 20 μm -45 μm；The hydroxyapatite particles account for note
The 10%-50% of the facial bulking agent compositions gel weight total amount of emitting beauty and shaping.
Optionally, further include in anesthetic, polyalcohols, vitamin, bacteriostatic agent, antioxidant or mineral salts one
Kind is several.
Optionally, anesthetic is lidocaine, and anesthetic accounts for the facial bulking agent compositions gel of injection-type beauty and shaping
The 0.05%-1% of weight total amount；Polyalcohol includes but not limited to sorbierite, glycerine, mannitol, propylene glycol, erythrol, wood
One or more in candy alcohol, maltitol and lactose alcohol, polyalcohol accounts for the facial filler combination of injection-type beauty and shaping
The 0.1%-15% of object gel weight total amount；Vitamin includes but not limited to vitamin C, vitamin E, vitamin B complex, vitamin
Account for the 0.1mg/mL-5.0mg/mL of the facial bulking agent compositions gel weight total amount of injection-type beauty and shaping；Bacteriostatic agent includes
One or more of thimerosal, benzalkonium bromide, anesin, benzyl alcohol or trityl ester, bacteriostatic agent account for injection-type beauty
The 0.01%-0.5% of the facial bulking agent compositions gel weight total amount of shaping.
The invention also discloses a kind of injection-type beauty and shaping preparation methods of facial bulking agent compositions gel, including
Following steps：Combined gels matrix is added in aqueous solution for injection under slow stirring, fully wetting swelling stands 6h, obtains
Clear transparent solutions or gel；Clear transparent solutions are added in hydroxyapatite particles either to grind in gel or stirring
10min makes it be mixed into a uniform phase, and the facial bulking agent compositions gel of injection-type beauty and shaping is prepared.
Compared with prior art, the present invention can be obtained including following technique effect：
1) the facial filled compositions of the beauty and shaping in the present invention, exist with gel form, include mainly hyaluronic acid
Sodium (HA) and cellulose ether derivatives.Sodium Hyaluronate and cellulose ether derivatives are mixed according to special ratios, it can
To obtain the gel of high elastic modulus and high dynamic viscosity.Using the hyaluronic acid good biocompatibility of non-crosslinked type, with fibre
The organic assembling of the plain ether derivative of dimension, can improve the persistence in injection site.
2) the facial filled compositions of beauty and shaping further include particulate (such as hydroxyapatite (CaHAP) particulate),
Using above-mentioned combined gels as carrier, the filling no two-phase section of industrial vacuum occurs, and provides the possibility of industrial mass production.
Even if viscosity declines after moist heat sterilization, hydroxyapatite particles are still dispersed in combined gels for a long time, while the combination
Object is easy to clinical injection.
Certainly, it implements any of the products of the present invention it is not absolutely required to while reaching all the above technique effect.
Description of the drawings
Attached drawing described herein is used to provide further understanding of the present invention, and constitutes the part of the present invention, this hair
Bright illustrative embodiments and their description are not constituted improper limitations of the present invention for explaining the present invention.In the accompanying drawings：
Fig. 1 is the elasticity of the gel combination of 1 content 2% of the embodiment of the present invention, 2 content 4% of embodiment and embodiment 9
Modulus；
Fig. 2 is the hydroxyapatite deposition situation after the mixed gel of content 1% in the embodiment of the present invention 1 is placed 60 days；
Fig. 3 is content 4% in the embodiment of the present invention 2, embodiment 9, embodiment 13,3 content 3% of embodiment and embodiment
The extrusion force of combined gels in 5.
Specific implementation mode
Carry out the embodiment that the present invention will be described in detail below in conjunction with embodiment, thereby to the present invention how application technology hand
Section solves technical problem and reaches the realization process of technical effect to fully understand and implement.
Injection-type beauty and shaping in the present invention is provided with facial filled compositions relative to well known filler many excellent
Point, including excellent biocompatibility, can be absorbed by physical safety, is desired as the facial filler holding of beauty and shaping
Machinery and the rheological equationm of state, at the same can stable for extended periods of time a uniform phase, can industrial vacuum it is filling and clinical be easy to inject.
According to the present invention, injection-type beauty and shaping is gel with facial bulking agent compositions.As used herein, term is " solidifying
Glue " generally refers to the material for the mobility for having between liquid and solid at room temperature.In addition, term " gel " is intended to table
The material (i.e. " glue ") of water can be absorbed by showing.In the present invention, injection-type beauty and shaping generally comprises life with facial filler
Acceptable carrier fluid in reason, the isotonic buffer solution of such as non-pyrogenic, such as sodium chloride solution, the phosphorus of 0.9% (w/w)
Hydrochlorate buffer solution (PBS), it is therefore preferable to the sodium chloride solution of 0.9% (w/w).
The invention discloses a kind of injection-type beauty and shaping facial bulking agent compositions gels, including combined gels matrix
And particulate.
Optionally, the combined gels matrix includes aqueous solution for injection, cellulose ethers or/and Sodium Hyaluronate,
Wherein, cellulose ethers account for the 0.5%-15% of the weight total amount of aqueous solution for injection, and Sodium Hyaluronate accounts for aqueous solution for injection
Weight total amount 0.1%-10%.
Further, cellulose ethers account for the 1%-6% of the weight total amount of aqueous solution for injection, and Sodium Hyaluronate accounts for injection
With the 0.1%-4% of the weight total amount of aqueous solution.
Optionally, the cellulose ethers are methylcellulose, sodium carboxymethylcellulose, ethyl cellulose, ethoxy
One or several kinds in cellulose, hydroxypropyl cellulose, hypromellose or cyanethyl cellulose.
Further, the cellulose ethers are sodium carboxymethylcellulose or/and methylcellulose.
Wherein, the sodium carboxymethylcellulose uses Bu Shi viscositys agent (Brookfield spindle
Viscometer (model LVDVC), at 25 DEG C, rotary speed is 50 rotating speeds (rpm) per minute, and shaft size is No. 63, is made
It is measured with 1% aqueous solution, the viscosity with 950 to 1100 milli pascal seconds (mPas).The wherein methyl
Cellulose using the agent of Bu Shi viscositys (Brookfield spindle viscometer (model LVDVC), at 25 DEG C, rotary speed
For 100 rotating speeds (rpm) per minute, shaft size is No. 63, is measured using 2% aqueous solution, has 950 to 1000 millis
The viscosity of pascal second (mPas).
Wherein, heretofore described hyaluronic acid is non-crosslinked type hyaluronic acid, it is preferable that average molecular weight is 0.1
×106Da to 5 × 106Da, particularly preferred average molecular weight is between 1 × 106Da to 3 × 106Da measures viscosity and uses Bu Shi
(Brookfield spindle viscometer (model LVDVC), at 25 DEG C, rotary speed is 30 or 50 per minute for viscosity agent
Rotating speed (rpm), shaft size are No. 64, are measured using 1% aqueous solution, have 1700 to 15000 milli Pascals
The viscosity of second (mPas).
Optionally, the aqueous solution for injection is that sodium chloride solution that mass concentration is 0.9% or phosphate-buffered are molten
Liquid.
Optionally, the particulate is hydroxyapatite particles.
Further, the average grain diameter of the hydroxyapatite particles is 5 μm -150 μm；The hydroxyapatite particles account for
The 10%-70% of the facial bulking agent compositions gel weight total amount of injection-type beauty and shaping.
Further, the average grain diameter of the hydroxyapatite particles is 20 μm -45 μm；The hydroxyapatite particles account for
The 10%-50% of the facial bulking agent compositions gel weight total amount of injection-type beauty and shaping.
Optionally, the facial bulking agent compositions gel of the injection-type beauty and shaping further includes anesthetic, polyalcohols, dimension
One or more of raw element, bacteriostatic agent, antioxidant or mineral salts.
Further, anesthetic especially local anesthetic, preferably lidocaine, anesthetic account for injection-type beauty and shaping
With the 0.05%-1% of facial bulking agent compositions gel weight total amount；Preferably 0.2%-0.6%.Polyalcohol includes but not
It is limited to sorbierite, glycerine, mannitol, propylene glycol, erythrol, xylitol, maltitol and one kind or more in lactose alcohol
It plants, in the present invention preferred glycerine, as moisturizer and lubricant, polyalcohol accounts for the facial filler of injection-type beauty and shaping
The 0.1%-15% of composition gels weight total amount, it is therefore preferable to 1%-5%.
The presence of vitamin can stimulate and maintain cell metabolism, thus can promote the generation of collagen.In the present invention
The middle vitamin used includes but not limited to vitamin C, vitamin E, vitamin B complex, i.e., one or more vitamin B1s, B2,
B3, B5, B6, B7, B9 and B12.Specifically, the concentration of vitamin C or vitamin E or vitamin B complex is preferably from about 0.1mg/mL-
5.0mg/mL.The common bacteriostatic agent that can be used for injecting includes thimerosal, benzalkonium bromide, anesin, benzyl alcohol, benzene methyl
Class considers that the bacteriostatic agent being used in the present invention is parabens, preferably from safety and incompatibility
The one or two of methyl p-hydroxybenzoate or propylparaben, bacteriostatic agent account for injection-type beauty and shaping and are filled out with face
Fill the 0.01%-0.5% of agent composition gels weight total amount.
The facial bulking agent compositions gel of injection-type beauty and shaping that the present invention is prepared has in following characteristic
One or more characteristics：
1) at the frequency (f) of 0.1 hertz (Hz) and 25 DEG C, loss tangent (G "/G') is 0.3 to 0.75；
2) at the frequency (f) of 0.1 hertz (Hz) and 25 DEG C, elasticity modulus (G') is 100 pas (Pa) to 240,000Pa；
3) at the frequency (f) of 0.1 hertz (Hz) and 25 DEG C, viscosity is 100Pas to 140,000Pas；
4) pH value is 6.5 to 7.5；
5) extrusion force is equal to or more than 0.3Kg (kilogram).
The facial bulking agent compositions gel of injection-type beauty and shaping that the present invention is prepared has desired rheology special
Property, i.e. high elastic modulus and dynamic viscosity, for replacing or filling biological tissue or increase the volume of biological tissue to reach
Desired cosmetic result, while being also easy to clinical injection.
Quality in the facial bulking agent compositions gel of injection-type beauty and shaping being prepared is uniform i.e. optional micro-
Particle hydroxyapatite particles are uniformly scattered in the composition always, do not occur two phase stratification, can be filling with industrial vacuum.
In addition, the beauty and shaping of the present invention is " injection-type " with facial bulking agent compositions.This indicates beauty and shaping face
Portion's bulking agent compositions are suitable for being injected in subcutaneous tissue and deep layer and periosteum, play certain filling effect and supporting role.
" injection-type " composition in meaning of the present invention can under normal pressure apply from syringe in normal condition.
In the examples below, unless otherwise stated, Sodium Hyaluronate (HA), referred to as H；Sodium carboxymethylcellulose sodium
(CMC-Na), referred to as C；Methylcellulose (MC), referred to as M；Hydroxyapatite (CaHAP), referred to as P；Then contain transparent
The gel of matter acid and hydroxyapatite is referred to as HP gels, contains hyaluronic acid, sodium carboxymethylcellulose sodium and hydroxyl phosphorus
The gel of lime stone is then referred to as HCP gels, and so on.Sodium Hyaluronate, sodium carboxymethylcellulose and sodium carboxymethylcellulose pyce
Concentration be to account for the weight percent of physiological saline.Hydroxyapatite average particle size is between 20 μm to 45 μm, hydroxyl
A concentration of total weight percent for accounting for gel combination of base apatite.Physiological saline is the note of the final concentration of 0.09g/L of sodium chloride
It penetrates and uses aqueous solution, referred to as solution A.
Embodiment 1 is with 1%, 2%, 4% hyaluronic acid and with the single gel of 30% hydroxyapatite particles
The preparation (comparing gel) of composition (HP).
Prepare the HP gel combinations of Sodium Hyaluronate a concentration of 1%.
1gHA is added to 100.9g solution As under slow stirring, fully wetting swelling stands 6h, obtains clear transparent solutions
Or gel.The then grinding of addition 43.67g hydroxyapatites or stirring 10min, make it be mixed into a uniform phase.
Formula ratio HA, hydroxyapatite and solution A are weighed according to formula in 1 embodiment 1 of table, preparation method is saturating with 1%
The preparation method of the HP gel combinations of bright matter acid sodium.
Table 1：The formula composition of embodiment 1,2,3
Embodiment 2 is with 1%, 3%, 5% methylcellulose (MC) and with 30% hydroxyapatite (CaHAP) particle
The preparation (comparing gel) of the single gel composition (MP) of son.
Specific formula is shown in Table 1 embodiment 2, the HP gel combinations of 1% Sodium Hyaluronate during the preparation method is the same as that of Example 1
Sodium Hyaluronate is replaced with the sodium carboxymethylcellulose pyce in the present embodiment by preparation method.
Embodiment 3 is with 2%, 4%, 6% sodium carboxymethylcellulose (CMC-Na) and with hydroxyapatite (CaHAP)
The preparation (comparing gel) of the single gel composition (CP) of particulate
Specific formula is shown in Table 1 embodiment 3, the HP gel combinations of 1% Sodium Hyaluronate during the preparation method is the same as that of Example 1
Sodium Hyaluronate is replaced with the methylcellulose in the present embodiment by preparation method.
Combined gels composition (MHP) of the embodiment 4 with 1%MC and 4%HA and with 30%CaHAP particulates
It prepares
100.9g solution As are added in 1g MC and 4g HA under slow stirring, fully wetting swelling stands 6h, obtains clear
Clear clear solution or gel.The then grinding of addition 45.38g hydroxyapatites or stirring 10min, make it be mixed into uniformly
One phase.
Combined gels composition (MHP) of the embodiment 5 with 3%MC and 1%HA and with 30%CaHAP particulates
It prepares
Specific preparation method is shown in embodiment 4, and the concrete content of MC, HA, CaHAP and solution A is shown in Table in 2 embodiments 5
Formula composition.
The formula composition of 2 embodiment 5,6,7 of table
Combined gels composition (MHP) of the embodiment 6 with 5%MC and 2%HA and with 50%CaHAP particulates
It prepares
Specific preparation method is shown in embodiment 4, and the concrete content of MC, HA, CaHAP and solution A is shown in Table in 2 embodiments 6
Formula composition.
Combined gels composition (MHP) of the embodiment 7 with 2%MC and 1%HA and with 10%CaHAP particulates
It prepares
Specific preparation method is shown in embodiment 4, and the concrete content of MC, HA, CaHAP and solution A is shown in Table in 2 embodiments 7
Formula composition.
Combined gels composition of the embodiment 8 with 2%CMC-Na and 1%HA and with 10%CaHAP particulates
(CHP) preparation
100.9g solution As are added in 2g CMC-Na and 1g HA under slow stirring, fully wetting swelling stands 6h,
Obtain clear transparent solutions or gel.The then grinding of addition 11.54g hydroxyapatites or stirring 10min, make it be mixed into
An even phase.
The formula composition of 3 embodiment 9,10,11 of table
Combined gels composition of the embodiment 9 with 4%CMC-Na and 2%HA and with 30%CaHAP particulates
(CHP) preparation
Specific preparation method is shown in embodiment 8, and the concrete content of CMC-NA, HA, CaHAP and solution A is shown in Table 3 embodiments 9
In formula composition.
Combined gels composition of the embodiment 10 with 6%CMC-NA and 1%HA and with 30%CaHAP particulates
(CHP) preparation
Specific preparation method is shown in embodiment 8, and the concrete content of CMC-NA, HA, CaHAP and solution A is shown in Table 3 embodiments 10
In formula composition.
Combined gels composition of the embodiment 11 with 4%CMC-NA and 4%HA and with 50%CaHAP particulates
(CHP) preparation
Specific preparation method is shown in embodiment 8, and the concrete content of CMC-NA, HA, CaHAP and solution A is shown in Table 3 embodiments 9
In formula composition.
Embodiment 12 is with 3%CMC-Na, 1%HA, 1% glycerine and with the combined gels of 30%CaHAP particulates
The preparation of composition (CHP)
1g glycerine is added in 100.9g solution As, is stirred and evenly mixed spare.
3g CMC-Na and 1g HA are added under slow stirring in above-mentioned solution, fully wetting swelling stands 6h, obtains
Clear transparent solutions or gel.The then grinding of addition 45.38g hydroxyapatites or stirring 10min, make it be mixed into uniformly
A phase.
Embodiment 13 is combined with 4%MC, 2%HA, 3% glycerine and with the combined gels of 30%CaHAP particulates
The preparation of object (MHP)
3g glycerine is added in 100.9g solution As, is stirred and evenly mixed spare.
4g MC and 2g HA are added under slow stirring in above-mentioned solution, fully wetting swelling stands 6h, must clarify
Clear solution or gel.The then grinding of addition 47.1g hydroxyapatites or stirring 10min, make it be mixed into uniform one
Phase.
Embodiment 14 is with 3%CMC-Na, 1%HA, 5% glycerine and with the combined gels of 30%CaHAP particulates
The preparation of composition (CHP)
5g glycerine is added in 100.9g solution As, is stirred and evenly mixed spare.
3g CMC-Na and 1g HA are added under slow stirring in above-mentioned solution, fully wetting swelling stands 6h, obtains
Clear transparent solutions or gel.The then grinding of addition 47.1g hydroxyapatites or stirring 10min, make it be mixed into uniformly
A phase.
Combined gels composition of the embodiment 15 with 15%MC and 0.1%HA and with 70%CaHAP particulates
(MHP) preparation
100.9g solution As are added in 15g MC and 0.1g HA under slow stirring, fully wetting swelling stands 6h, obtains
Clear transparent solutions or gel.The then grinding of addition 270.67g hydroxyapatites or stirring 10min, make it be mixed into
An even phase；Wherein, the average grain diameter of hydroxyapatite particles is 5 μm.
Combined gels composition of the embodiment 16 with 0.5%MC and 10%HA and with 10%CaHAP particulates
(MHP) preparation
100.9g solution As are added in 0.5g MC and 10g HA under slow stirring, fully wetting swelling stands 6h, obtains
Clear transparent solutions or gel.The then grinding of addition 12.38g hydroxyapatites or stirring 10min, make it be mixed into uniformly
A phase；Wherein, the average grain diameter of hydroxyapatite particles is 150 μm.
17 viscosity of embodiment
Since increased viscosity will limit extension of the gel in soft tissue, and it also will be helpful to the increased effect of volume
Fruit, therefore viscosity is the important parameter of bulking agent compositions.In this embodiment, the viscosity number of detection combination gel and compare
The viscosity of combined gels and single gel.For this purpose, to above-described embodiment 1 to embodiment 16 carry out viscosity measurement (at 25 DEG C, frequency
From 0.1Hz to 1Hz, panel size PP35,2 μm of gap size, Haake rotational rheometer).It is found that (at 25 DEG C, under 0.1Hz),
Combined gels viscosity in embodiment 4 to embodiment 16 is equal to or is more than 120Pas, is all higher than under the conditions of same amount
Single gel (embodiment 1 to embodiment 3), as in table 4 embodiment viscosity compare.
Table 4
| Embodiment | Viscosity/Pas |
| Embodiment 3, content 4% | 541.2 |
| Embodiment 9 | 5118.4 |
| 2 content of embodiment is 3% | 172.8 |
| Embodiment 5 | 787.2 |
18 elasticity modulus of embodiment
Since the drawing that elasticity modulus influences filler puies forward ability, the maintenance of elasticity modulus is quite important.Implement herein
In example, the elasticity modulus of detection combination gel, the elasticity modulus of loss tangent and comparison combination gel and single gel.
Carrying out modulus measurements to above-described embodiment 1 to embodiment 16, (at 25 DEG C, frequency is from 0.1Hz to 1Hz, panel size PP35, gap
2 μm of size, Haake rotational rheometer).It is found that (at 25 DEG C, under 0.1Hz), the combined gels in embodiment 4 to embodiment 16
Elasticity modulus is equal to or is more than 100Pa, the single gel (embodiment 1 to embodiment 3) being all higher than under the conditions of same amount.
In addition, the elasticity modulus that increases combined gels of the cellulose ethers relative to hyaluronic acid by a relatively large margin in combined gels, is shown in
Fig. 1.Embodiment 4 to 16 combined gels of embodiment loss tangent between 0.3 to 0.75, show the combined gels simultaneously
Plasticity with good liquid fluidity and solid, can be used as good cosmetic filler.
19 vacuum filling of embodiment
By in embodiment 1 to embodiment 16 gel carry out vacuum outgas, exclude bubble to reach Clinical practice purpose, after
Embedding pressurize in syringe or in test tube.It has been found that the moisture in Vacuum Degassing Process of the independent gel in embodiment 1 is big
Amount is lost in, and heterogeneous area is occurred, that is, is divided into two-phase, and upper layer is pulverulent solids, is blocked encapsulating device, can not be carried out filling.It is real
The combined gels applied in example 4 to embodiment 16 do not occur the above situation, are all a uniform phase, table in entire potting process
The addition of light fibers element ethers enhances the water lock ability of the combined gels, which can be used for industrial mass production.
20 stability of embodiment
Hydroxyapatite can be intended to deposit with the time, and this deposition causes to obtain the hydroxyl phosphorus based on heterogeneous particle
Lime stone product, the product are unsatisfactory for the behavior (due to clog needle) by needle injected gel, are also unsatisfactory for preparation in injection site
Safety and performance (the notable risk of complication).Therefore to embedding gel high-pressure moist heat sterilization (121 in embodiment 18
DEG C, 15min), the deposition of 60 days observation hydroxyapatites is placed under the conditions of constant temperature (4 DEG C, 25 DEG C).It has been found that implementing
Example 4 to 16 combined gels of embodiment remain that a stable phase, hydroapatite particles are dispersed in wherein always.Implement
Content is 1%, 2% in example 1, and 2% gel of content finds two-phase section, i.e. hydroxyl in content 1% and embodiment 3 in embodiment 2
Apatite deposition, such as Fig. 2, Fig. 2 are the hydroxyapatite deposition after the mixed gel of content 1% in embodiment 1 is placed 60 days
Situation, it is observed that apparent two-phase section.
21 extrusion force of embodiment
Combined gels in the present invention are injection-type gel, and extrusion force is most important for Clinical practice.Therefore it detects real
Apply the extrusion force of the product in syringe of embedding in example 18.It is found that (1mL syringes, the syringe needle of 20G, rate of extrusion
100mm/min), the addition of hyaluronic acid reduces the extrusion force of cellulose ether gellike, and the addition of glycerine similarly reduces
The extrusion force of combined gels, is shown in Fig. 3.
Therefore, the experimental data that above-described embodiment is provided fully demonstrates the filled compositions in the present invention and can use
In clinical beautifying medical, persistence and La Ti abilities are provided, while can be used for industrial scale production.
Above description has shown and described several preferred embodiments of invention, but as previously described, it should be understood that invention is not
It is confined to form disclosed herein, is not to be taken as excluding other embodiments, and can be used for various other combinations, modification
And environment, and can be carried out by the above teachings or related fields of technology or knowledge in the scope of the invention is set forth herein
Change.And changes and modifications made by those skilled in the art do not depart from the spirit and scope of invention, then should all be weighed appended by invention
In the protection domain that profit requires.
Claims (10)
1. a kind of facial bulking agent compositions gel of injection-type beauty and shaping, which is characterized in that including combined gels matrix and
Hydroxyapatite particles.
2. the facial bulking agent compositions gel of injection-type beauty and shaping according to claim 1, which is characterized in that described
Combined gels matrix include aqueous solution for injection, cellulose ethers or/and Sodium Hyaluronate, wherein cellulose ethers account for note
The 0.5%-15% of the weight total amount with aqueous solution is penetrated, Sodium Hyaluronate accounts for the 0.1%- of the weight total amount of aqueous solution for injection
10%.
3. the facial bulking agent compositions gel of injection-type beauty and shaping according to claim 2, which is characterized in that fiber
Plain ethers accounts for the 1%-6% of the weight total amount of aqueous solution for injection, and Sodium Hyaluronate accounts for the weight total amount of aqueous solution for injection
0.1%-4%.
4. the facial bulking agent compositions gel of injection-type beauty and shaping according to claim 2, which is characterized in that described
Cellulose ethers be methylcellulose, sodium carboxymethylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose,
One or several kinds in hypromellose or cyanethyl cellulose.
5. the facial bulking agent compositions gel of injection-type beauty and shaping according to claim 2, which is characterized in that described
Aqueous solution for injection be sodium chloride solution or phosphate buffer solution that mass concentration is 0.9%.
6. the facial bulking agent compositions gel of injection-type beauty and shaping according to claim 2, which is characterized in that described
The average grain diameter of hydroxyapatite particles is 5 μm -150 μm；The hydroxyapatite particles account for injection-type beauty and shaping face
The 10%-70% of bulking agent compositions gel weight total amount.
7. the facial bulking agent compositions gel of injection-type beauty and shaping according to claim 2, which is characterized in that described
The average grain diameter of hydroxyapatite particles is 20 μm -45 μm；The hydroxyapatite particles account for injection-type beauty and shaping face
The 10%-50% of bulking agent compositions gel weight total amount.
8. the facial bulking agent compositions gel of injection-type beauty and shaping according to any one of claim 1 to 7,
It is characterized in that, further includes one kind or several in anesthetic, polyalcohols, vitamin, bacteriostatic agent, antioxidant or mineral salts
Kind.
9. the facial bulking agent compositions gel of injection-type beauty and shaping according to claim 8, which is characterized in that anesthesia
Agent is lidocaine, and anesthetic accounts for the 0.05%- of the facial bulking agent compositions gel weight total amount of injection-type beauty and shaping
1%；Polyalcohol include but not limited to sorbierite, glycerine, mannitol, propylene glycol, erythrol, xylitol, maltitol and
One or more in lactose alcohol, polyalcohol accounts for the facial bulking agent compositions gel weight total amount of injection-type beauty and shaping
0.1%-15%；Vitamin includes but not limited to vitamin C, vitamin E, vitamin B complex, and vitamin accounts for injection-type beauty and shaping
With the 0.1mg/mL-5.0mg/mL of facial bulking agent compositions gel weight total amount；Bacteriostatic agent include thimerosal, benzalkonium bromide,
One or more of anesin, benzyl alcohol or trityl ester, bacteriostatic agent account for the facial filler of injection-type beauty and shaping
The 0.01%-0.5% of composition gels weight total amount.
10. a kind of injection-type beauty and shaping preparation method of facial bulking agent compositions gel, which is characterized in that including following
Step：Combined gels matrix is added in aqueous solution for injection under slow stirring, fully wetting swelling stands 6h, must clarify
Clear solution or gel；Clear transparent solutions are added in hydroxyapatite particles either to grind in gel or stirring
10min makes it be mixed into a uniform phase, and the facial bulking agent compositions gel of injection-type beauty and shaping is prepared.
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110279889A (en) * | 2019-08-13 | 2019-09-27 | 福建拓烯新材料科技有限公司 | A kind of beauty pharmaceutical composition containing sodium hyaluronate |
| CN110292655A (en) * | 2019-07-18 | 2019-10-01 | 王月玲 | A kind of injection fillers preparation of hydroxyl apatite and preparation method thereof |
| CN110327497A (en) * | 2019-07-31 | 2019-10-15 | 易浦润（上海）生物技术有限公司 | A kind of injection gel and preparation method thereof containing microballoon |
| CN110787319A (en) * | 2019-11-19 | 2020-02-14 | 上海摩漾生物科技有限公司 | Implant for facial cosmetic lifting and application thereof |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1740233A1 (en) * | 2004-03-08 | 2007-01-10 | Dr.h.c. Robert Mathys Stiftung | Hydraulic cement based on calcium phosphate for surgical use |
| US20100172829A1 (en) * | 2009-01-03 | 2010-07-08 | Anderson Russell J | Enhanced carriers for the delivery of microparticles to bodily tissues and fluids |
| CN104130424A (en) * | 2014-05-30 | 2014-11-05 | 天津科技大学 | Preparation method for hyaluronic acid/bacterial cellulose composite hydrogel |
| CN104703582A (en) * | 2012-10-08 | 2015-06-10 | 安特易斯有限公司 | Injectable sterile aqueous formulation based on crosslinked hyaluronic acid and hydroxyapatite for aesthetic use |
| CN105330902A (en) * | 2015-11-20 | 2016-02-17 | 清华大学 | Hyaluronic acid-methyl cellulose composite hydrogel as well as preparation and application thereof |
| CN106421929A (en) * | 2016-09-22 | 2017-02-22 | 四川大学 | Injectable calcium phosphate/natural polymer composite material and preparation method and application thereof |
| CN107383397A (en) * | 2017-07-26 | 2017-11-24 | 武汉理工大学 | To aoxidize hydroxyethyl cellulose as derivatives of hyaluronic acids self-crosslinking hydrogel of crosslinking agent and preparation method thereof |
-
2018
- 2018-06-15 CN CN201810620176.5A patent/CN108744054A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1740233A1 (en) * | 2004-03-08 | 2007-01-10 | Dr.h.c. Robert Mathys Stiftung | Hydraulic cement based on calcium phosphate for surgical use |
| US20100172829A1 (en) * | 2009-01-03 | 2010-07-08 | Anderson Russell J | Enhanced carriers for the delivery of microparticles to bodily tissues and fluids |
| CN104703582A (en) * | 2012-10-08 | 2015-06-10 | 安特易斯有限公司 | Injectable sterile aqueous formulation based on crosslinked hyaluronic acid and hydroxyapatite for aesthetic use |
| CN104130424A (en) * | 2014-05-30 | 2014-11-05 | 天津科技大学 | Preparation method for hyaluronic acid/bacterial cellulose composite hydrogel |
| CN105330902A (en) * | 2015-11-20 | 2016-02-17 | 清华大学 | Hyaluronic acid-methyl cellulose composite hydrogel as well as preparation and application thereof |
| CN106421929A (en) * | 2016-09-22 | 2017-02-22 | 四川大学 | Injectable calcium phosphate/natural polymer composite material and preparation method and application thereof |
| CN107383397A (en) * | 2017-07-26 | 2017-11-24 | 武汉理工大学 | To aoxidize hydroxyethyl cellulose as derivatives of hyaluronic acids self-crosslinking hydrogel of crosslinking agent and preparation method thereof |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110292655A (en) * | 2019-07-18 | 2019-10-01 | 王月玲 | A kind of injection fillers preparation of hydroxyl apatite and preparation method thereof |
| CN110327497A (en) * | 2019-07-31 | 2019-10-15 | 易浦润（上海）生物技术有限公司 | A kind of injection gel and preparation method thereof containing microballoon |
| CN110279889A (en) * | 2019-08-13 | 2019-09-27 | 福建拓烯新材料科技有限公司 | A kind of beauty pharmaceutical composition containing sodium hyaluronate |
| CN110787319A (en) * | 2019-11-19 | 2020-02-14 | 上海摩漾生物科技有限公司 | Implant for facial cosmetic lifting and application thereof |
| CN111249189A (en) * | 2020-01-15 | 2020-06-09 | 陈勇 | An injectable facial filler composition for skin care and plastic, and its preparation method |
| WO2021156345A1 (en) * | 2020-02-06 | 2021-08-12 | Merz Pharma Gmbh & Co. Kgaa | Injectable composition for skin and soft tissue augmentation |
| CN111249525A (en) * | 2020-03-25 | 2020-06-09 | 宁波赛缪斯生物科技有限公司 | Injectable facial filler composition gel for cosmetic and plastic surgery and preparation method thereof |
| CN112294668A (en) * | 2020-06-30 | 2021-02-02 | 西安博和医疗科技有限公司 | Hyaluronic acid injection |
| CN112294668B (en) * | 2020-06-30 | 2024-04-02 | 西安博和医疗科技有限公司 | Hyaluronic acid injection |
| CN113230452A (en) * | 2021-05-28 | 2021-08-10 | 易生彬 | Face filler and preparation method thereof |
| CN115382011A (en) * | 2021-07-01 | 2022-11-25 | 意瑞生物科技(苏州)有限公司 | Skin injection filler gel and preparation process thereof |
| CN113941027A (en) * | 2021-10-21 | 2022-01-18 | 珠海美如初医疗美容有限公司 | Injectable facial filler composition gel for cosmetic and plastic surgery and preparation method thereof |
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