CN106496599A - High viscosity hyaluronic acid sodium gel and preparation method thereof - Google Patents
High viscosity hyaluronic acid sodium gel and preparation method thereof Download PDFInfo
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
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Abstract
The invention discloses high viscosity hyaluronic acid sodium gel and preparation method thereof.Specifically, high viscosity hyaluronic acid sodium gel of the invention includes the following component in terms of mass concentration：The Sodium Hyaluronate of 20～40g/L, the anionic surfactant of 0.01～0.05g/L, the rheology control agent of 0.3～1.0g/L, the glycerine of 0.5～1.5g/L, balance of water for injection, wherein：The molecular weight of the Sodium Hyaluronate is 200～4,000,000 dalton.The gel is mainly prepared from by the Sodium Hyaluronate of high concentration, HMW, by adding multiple auxiliary agents such as anionic surfactant, rheology control agent, glycerine, so that the gel has higher viscoplasticity and more preferable rheological properties, can effectively prevent or reduce postoperative adhesions problem, there is good application prospect in field of medicaments.
Description
Technical field
The invention belongs to pharmaceutical technology field, is related to a kind of high viscosity hyaluronic acid sodium gel and preparation method thereof.
Background technology
1934, Karl professors Mayer extracted hyaluronic acid first in bovine vitreous body.Grinding through many decades
Study carefully, it has been found which is widely present in people and other vertebrate connective tissues, such as space between cells, movable joint group
Knit, all contain hyaluronic acid in the tissue such as umbilical cord, skin, cartilage, vascular wall, synovia and cockscomb and organ.
Hyaluronic acid belongs to linear polymeric polysaccharide, contains disaccharides repetitive, the glucose in repetitive in structure
Aldehydic acid is connected with N-Acetyl-D-glucosamine by β -1,3 glycosidic bonds, and thousands of disaccharides repetitive passes through β-Isosorbide-5-Nitrae glycosidic bond
It is connected, forms whole macromolecule linear chain structure, its structure is as follows.
In physiological conditions, the carboxyl in hyaluronan molecule is combined rear as hyalomitome in free state with sodium ion
Sour sodium.Sodium Hyaluronate intramolecular do not contain sulfate group, also not with protein covalent bond, can be in the form of free chain in body
Interior free presence, and which is random coil state in the solution, and with good hydrodynamic characteristics, it is heavy that this gives which
The physical characteristic that wants, i.e. height viscoplasticity, plasticity, permeability and good biocompatibility so as in medicine
Unique effect is played.
Hyaluronic acid sodium gel is widely used in fields such as orthopaedics, ophthalmology, gynaecology and department of plastic surgery.Except as eye-drops preparations
Carrier and as eye-drops preparations beyond, Sodium Hyaluronate also has important application in ophthalmologic operation.With deepening continuously for research,
Sodium Hyaluronate application clinically expanded to cataract extraction, detachment of retina, corneal transplantation, ophthalmic crystal be implanted into,
Anti-glaucoma, cornea preset, cyclodialysis cleft and eye traumas etc. more than 20 plant operation.Sodium Hyaluronate or knuckle synovia and cartilage
Important composition composition, by improve joint in Sodium Hyaluronate content, can increase joint fluid toughness and lubrication work(
Can, protection cartilage is played, promoted joint healing and regeneration, pain of alleviation, increased the effect such as range of motion.Report both at home and abroad
Knee joint osseous arthritis, the periarthritis of shoulderjoint, Kaschin-Beck disease, rheumatoid is treated using Sodium Hyaluronate replacement therapy in road
Arthritis, Chondromalacia of patella, especially treat knee joint osseous arthritis in intraarticular injection Sodium Hyaluronate and have taken
Obtain significant curative effect.Hyaluronic acid and its sodium salt content in peritoneal fluid, uterine fluid and Oviductal Fluid is decide to a great extent
Abdominal cavity, uterus and oviducal physiological function, the viscoelasticity of liquid affect the physiological function of female genital tract and preventing for itself
Imperial ability, and the quality of these liquid and how many molecular weight and concentration for depending on wherein hyaluronic acid and its sodium salt.Therefore,
When using laparoscope, hysteroscope, the postoperative obstruction that may occur and adhesion can be reduced using hyaluronic acid and its sodium salt
Complication, and the reparation on acceleration of wound surface.Substantial amounts of zoopery and clinical practice show, are preventing and reducing gynemetrics's hand
In terms of the adhesion that art is caused, hyaluronic acid and its sodium salt are a kind of safe and effective desirable materials.
Research shows, when hyaluronan molecule is sufficiently large, it becomes possible to form network structure, which forms cancellated energy
Power is affected by molecular weight.The hyaluronic acid of low-molecular-weight is only capable of the network structure to form fragment shape in low concentration, and high
The hyaluronic acid of molecular weight can form the network structure for covering whole system.When being mixed in the hyaluronic acid solution of HMW
During the hyaluronic acid of low-molecular-weight, can greatly change the rheological property of hyaluronic acid solution.Hyaluronic acid is molten in low concentration
In liquid, its molecule can arbitrarily be crimped and form viscoplasticity transparent colloid, and then there is in highly concentrated solution stronger film forming
Property.Therefore, in the urgent need to a kind of high concentration of offer, the hyaluronic acid sodium gel of HMW, the gel should have higher gluing
Elastic and more preferable rheological properties, and then preferably application is played in field of medicaments.
Content of the invention
For above-mentioned situation, it is an object of the invention to provide a kind of high viscosity hyaluronic acid sodium gel and its preparation side
Method.Sodium Hyaluronate containing high concentration, HMW in the hyaluronic acid sodium gel of the present invention, and made by adding auxiliary agent
Obtain gel of the invention and there are higher viscoplasticity and more preferable rheological properties.
To achieve these goals, the present invention adopts following technical proposal：
A kind of high viscosity hyaluronic acid sodium gel, which includes the following component in terms of mass concentration：20～40g/L's is transparent
Matter acid sodium, the anionic surfactant of 0.01～0.05g/L, the rheology control agent of 0.3～1.0g/L, 0.5～1.5g/L
Glycerine, balance of water for injection, wherein：The molecular weight of the Sodium Hyaluronate is 200～4,000,000 dalton.In shearing speed
Rate is 0.01Hz, under conditions of temperature is 25 DEG C, the shear viscosity of above-mentioned high viscosity hyaluronic acid sodium gel can reach 2 ×
106More than mPa s.
Preferably, in above-mentioned high viscosity hyaluronic acid sodium gel, the Sodium Hyaluronate extract from animal tissue or
Person is produced by bacterial fermentation process.
Preferably, in above-mentioned high viscosity hyaluronic acid sodium gel, the anionic surfactant is alkyl phosphoric acid
Ester sylvite or alkyl sodium phosphate.
Preferably, in above-mentioned high viscosity hyaluronic acid sodium gel, the rheology control agent is Carbomer.
In a preferred embodiment, above-mentioned high viscosity hyaluronic acid sodium gel also includes osmotic pressure regulator (such as
Sodium chloride, potassium chloride, glucose, sodium citrate etc.), which adjusts the osmotic pressure of the gel to 250～350mOsmol L-1.
Preferably, in above-mentioned high viscosity hyaluronic acid sodium gel, the osmotic pressure regulator is sodium chloride.
In a preferred embodiment, above-mentioned high viscosity hyaluronic acid sodium gel also includes pH value regulator (such as hydrogen
Sodium oxide molybdena, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium carbonate, sodium acid carbonate, hydrochloric acid etc.), its by the pH value of the gel adjust to
6.8～7.8.
Preferably, in above-mentioned high viscosity hyaluronic acid sodium gel, the pH value regulator is disodium hydrogen phosphate/di(2-ethylhexyl)phosphate
Hydrogen sodium buffering is right.
A kind of preparation method of above-mentioned high viscosity hyaluronic acid sodium gel, which comprises the steps：
1) according to formula in consumption weigh various components；
2) anionic surfactant, rheology control agent, glycerine are added in water for injection, are carried out after being completely dissolved
Aseptic filtration and high pressure steam sterilization, obtain gel carrier；
3) by step 2) in obtain gel carrier cooling, under clean environment, add in the gel carrier transparent
Matter acid sodium is simultaneously stirred, until Sodium Hyaluronate is completely dissolved, obtains high viscosity hyaluronic acid sodium gel.
Preferably, in above-mentioned preparation method, step 2) described in aseptic filtration using sterilized 0.22 μm of filter core come
Complete.
Preferably, in above-mentioned preparation method, step 2) described in the temperature of high pressure steam sterilization be 121 DEG C, the time is
30 minutes.
Preferably, in above-mentioned preparation method, step 3) described in cool down after temperature be 40～60 DEG C.
Preferably, in above-mentioned preparation method, step 3) described in clean environment cleanliness factor more than hundred grades.
Preferably, in above-mentioned preparation method, step 3) described in stir and completed using agitator tank, mixing speed exists
Below 200rpm.
In a preferred embodiment, above-mentioned preparation method also include by the high viscosity hyaluronic acid sodium gel without
Bacterium filling into preparation the step of.
Preferably, in above-mentioned preparation method, before the sterile filling, first the high viscosity Sodium Hyaluronate is coagulated
Glue is heated to 60～80 DEG C, its object is to the viscosity for reducing immediately product, so that follow-up filling operation can be smoothed out.
Compared with prior art, there are following advantages using the present invention of above-mentioned technical proposal：
The hyaluronic acid of low-molecular-weight is only capable of the network structure to form fragment shape in low concentration, and HMW is transparent
Matter acid molecule can form the network structure for covering whole system.In low concentration solution, hyaluronan molecule arbitrarily can be rolled up
Bent and form viscoelastic transparent colloid, and then there is in highly concentrated solution stronger film forming.Transparent when HMW
Be mixed in matter acid solution low-molecular-weight hyaluronic acid when, can greatly change hyaluronic acid solution rheological property.Therefore,
High viscosity hyaluronic acid sodium gel provided by the present invention is mainly prepared from by the Sodium Hyaluronate of high concentration, HMW,
By adding multiple auxiliary agents such as anionic surfactant, rheology control agent, glycerine so that the gel has higher viscoelastic
Property and more preferable rheological properties, can effectively prevent or reduce postoperative adhesions problem, there is well application in field of medicaments
Prospect.In addition, gel process for preparing provided by the present invention has the advantages that simple and convenient, equipment requirement is low, raw material are easy to get,
Solve high concentration, high molecular weight sodium hyaluronate and finely dispersed problem is difficult in course of dissolution, be suitable for extensive work
Industry metaplasia is produced.
Specific embodiment
Below in conjunction with specific embodiments to the present invention in technical scheme make further description, but following enforcement
Example should not be considered as limiting protection scope of the present invention.In addition to specified otherwise, instrument used in the following example,
Reagent, material etc. can pass through conventional commercial means and obtain.
Embodiment 1：The preparation of high viscosity hyaluronic acid sodium gel preparation.
(1) water for injection 1000mL is added in container, be subsequently adding 1-isobutyl-3,5-dimethylhexylphosphoric acid sylvite 0.01g, card
Ripple nurse 0.3g, glycerine 0.5g, disodium hydrogen phosphate 0.45g, sodium dihydrogen phosphate 0.20g and sodium chloride 7.0g, with after being completely dissolved
0.22 μm of filter core of sterilizing carries out aseptic filtration, is placed in high-pressure steam sterilizing pan sterilizing 30 minutes in 121 DEG C, obtains gel
Carrier；
(2) above-mentioned gel carrier is cooled to 40 DEG C, under hundred grades of cleanliness factor environment, gel carrier is added to stirring first
In tank, under 40 DEG C of heat-retaining conditions, then degerming for Sodium Hyaluronate that molecular weight is 3,560,000 dalton dry powder 20.0g is slowly added
Enter in agitator tank, mixing speed is slowly improved to 200rpm, until Sodium Hyaluronate is completely dissolved, obtain high viscosity hyaluronic acid
Sodium gel；
(3) aseptically above-mentioned gel is carried out filling, filling front hyaluronic acid sodium gel is heated to 60 DEG C first,
After the completion of filling, high viscosity hyaluronic acid sodium gel preparation is obtained final product.
The pH of the high viscosity hyaluronic acid sodium gel prepared by said method is 7.2, and osmotic pressure is 289mOsmol L-1.It is 0.01Hz in shear rate, under conditions of temperature is 25 DEG C, the shear viscosity of the gel is 2.578 × 106mPa·s.
Embodiment 2：The preparation of high viscosity hyaluronic acid sodium gel preparation.
(1) water for injection 1000mL is added in container, be subsequently adding 1-isobutyl-3,5-dimethylhexylphosphoric acid sylvite 0.03g, card
Ripple nurse 0.6g, glycerine 1.0g, disodium hydrogen phosphate 0.45g, sodium dihydrogen phosphate 0.20g and sodium chloride 7.0g, with after being completely dissolved
0.22 μm of filter core of sterilizing carries out aseptic filtration, is placed in high-pressure steam sterilizing pan sterilizing 30 minutes in 121 DEG C, obtains gel
Carrier；
(2) above-mentioned gel carrier is cooled to 50 DEG C, under hundred grades of cleanliness factor environment, gel carrier is added to stirring first
In tank, under 50 DEG C of heat-retaining conditions, then degerming for Sodium Hyaluronate that molecular weight is 2,880,000 dalton dry powder 30.0g is slowly added
Enter in agitator tank, mixing speed is slowly improved to 200rpm, until Sodium Hyaluronate is completely dissolved, obtain high viscosity hyaluronic acid
Sodium gel；
(3) aseptically above-mentioned gel is carried out filling, filling front hyaluronic acid sodium gel is heated to 70 DEG C first,
After the completion of filling, high viscosity hyaluronic acid sodium gel preparation is obtained final product.
The pH of the high viscosity hyaluronic acid sodium gel prepared by said method is 7.3, and osmotic pressure is 305mOsmol L-1.It is 0.01Hz in shear rate, under conditions of temperature is 25 DEG C, the shear viscosity of the gel is 4.103 × 106mPa·s.
Embodiment 3：The preparation of high viscosity hyaluronic acid sodium gel preparation.
(1) water for injection 1000mL is added in container, be subsequently adding 1-isobutyl-3,5-dimethylhexylphosphoric acid sylvite 0.05g, card
Ripple nurse 1.0g, glycerine 1.5g, disodium hydrogen phosphate 0.45g, sodium dihydrogen phosphate 0.20g and sodium chloride 7.0g, with after being completely dissolved
0.22 μm of filter core of sterilizing carries out aseptic filtration, is placed in high-pressure steam sterilizing pan sterilizing 30 minutes in 121 DEG C, obtains gel
Carrier；
(2) above-mentioned gel carrier is cooled to 60 DEG C, under hundred grades of cleanliness factor environment, gel carrier is added to stirring first
In tank, under 60 DEG C of heat-retaining conditions, then degerming for Sodium Hyaluronate that molecular weight is 2,120,000 dalton dry powder 38.0g is slowly added
Enter in agitator tank, mixing speed is slowly improved to 200rpm, until Sodium Hyaluronate is completely dissolved, obtain high viscosity hyaluronic acid
Sodium gel；
(3) aseptically above-mentioned gel is carried out filling, filling front hyaluronic acid sodium gel is heated to 80 DEG C first,
After the completion of filling, high viscosity hyaluronic acid sodium gel preparation is obtained final product.
The pH of the high viscosity hyaluronic acid sodium gel prepared by said method is 7.3, and osmotic pressure is 323mOsmol L-1.It is 0.01Hz in shear rate, under conditions of temperature is 25 DEG C, the shear viscosity of the gel is 5.578 × 106mPa·s.
Embodiment 4：The preparation of high viscosity hyaluronic acid sodium gel preparation.
(1) water for injection 1000mL is added in container, be subsequently adding 1-isobutyl-3,5-dimethylhexylphosphoric acid sylvite 0.03g, card
Ripple nurse 0.6g and glycerine 1.0g, carries out aseptic filtration with sterilized 0.22 μm of filter core after being completely dissolved, is placed in high steam
Sterilize 30 minutes in 121 DEG C in autoclave, obtain gel carrier；
(2) above-mentioned gel carrier is cooled to 50 DEG C, under hundred grades of cleanliness factor environment, gel carrier is added to stirring first
In tank, under 50 DEG C of heat-retaining conditions, then degerming for Sodium Hyaluronate that molecular weight is 3,560,000 dalton dry powder 30.0g is slowly added
Enter in agitator tank, mixing speed is slowly improved to 200rpm, until Sodium Hyaluronate is completely dissolved, obtain high viscosity hyaluronic acid
Sodium gel；
(3) aseptically above-mentioned gel is carried out filling, filling front hyaluronic acid sodium gel is heated to 70 DEG C first,
After the completion of filling, high viscosity hyaluronic acid sodium gel preparation is obtained final product.
The high viscosity hyaluronic acid sodium gel prepared by said method is 0.01Hz in shear rate, and temperature is 25 DEG C
Under the conditions of shear viscosity be 3.875 × 106mPa·s.
Embodiment 5：The preparation of high viscosity hyaluronic acid sodium gel preparation.
(1) water for injection 1000mL is added in container, be subsequently adding 1-isobutyl-3,5-dimethylhexylphosphoric acid sylvite 0.03g, card
Ripple nurse 0.6g, glycerine 1.0g, disodium hydrogen phosphate 0.45g and sodium dihydrogen phosphate 0.20g, with sterilized 0.22 μm after being completely dissolved
Filter core carries out aseptic filtration, is placed in high-pressure steam sterilizing pan sterilizing 30 minutes in 121 DEG C, obtains gel carrier；
(2) above-mentioned gel carrier is cooled to 50 DEG C, under hundred grades of cleanliness factor environment, gel carrier is added to stirring first
In tank, under 50 DEG C of heat-retaining conditions, then degerming for Sodium Hyaluronate that molecular weight is 3,560,000 dalton dry powder 30.0g is slowly added
Enter in agitator tank, mixing speed is slowly improved to 200rpm, until Sodium Hyaluronate is completely dissolved, obtain high viscosity hyaluronic acid
Sodium gel；
(3) aseptically above-mentioned gel is carried out filling, filling front hyaluronic acid sodium gel is heated to 70 DEG C first,
After the completion of filling, high viscosity hyaluronic acid sodium gel preparation is obtained final product.
The pH of the high viscosity hyaluronic acid sodium gel prepared by said method is 7.1.It is 0.01Hz in shear rate, warm
Under conditions of spending for 25 DEG C, the shear viscosity of the gel is 3.955 × 106mPa·s.
Embodiment 6：The preparation of high viscosity hyaluronic acid sodium gel preparation.
(1) water for injection 1000mL is added in container, be subsequently adding 1-isobutyl-3,5-dimethylhexylphosphoric acid sylvite 0.03g, card
Ripple nurse 0.6g, glycerine 1.0g and sodium chloride 7.0g, carry out aseptic filtration, juxtaposition with sterilized 0.22 μm of filter core after being completely dissolved
Sterilize 30 minutes in 121 DEG C in high-pressure steam sterilizing pan, obtain gel carrier；
(2) above-mentioned gel carrier is cooled to 50 DEG C, under hundred grades of cleanliness factor environment, gel carrier is added to stirring first
In tank, under 50 DEG C of heat-retaining conditions, then degerming for Sodium Hyaluronate that molecular weight is 3,560,000 dalton dry powder 30.0g is slowly added
Enter in agitator tank, mixing speed is slowly improved to 200rpm, until Sodium Hyaluronate is completely dissolved, obtain high viscosity hyaluronic acid
Sodium gel；
(3) aseptically above-mentioned gel is carried out filling, filling front hyaluronic acid sodium gel is heated to 70 DEG C first,
After the completion of filling, high viscosity hyaluronic acid sodium gel preparation is obtained final product.
The osmotic pressure of the high viscosity hyaluronic acid sodium gel prepared by said method is 311mOsmol L-1.In shearing
Speed is 0.01Hz, and under conditions of temperature is 25 DEG C, the shear viscosity of the gel is 4.126 × 106mPa·s.
Claims (10)
1. a kind of high viscosity hyaluronic acid sodium gel, which includes the following component in terms of mass concentration：The hyalomitome of 20～40g/L
Sour sodium, the anionic surfactant of 0.01～0.05g/L, the rheology control agent of 0.3～1.0g/L, 0.5～1.5g/L
Glycerine, balance of water for injection, wherein：The molecular weight of the Sodium Hyaluronate is 200～4,000,000 dalton.
2. high viscosity hyaluronic acid sodium gel according to claim 1, it is characterised in that：
The anionic surfactant is potassium alkyl phosphate or alkyl sodium phosphate.
3. high viscosity hyaluronic acid sodium gel according to claim 1, it is characterised in that：
The rheology control agent is Carbomer.
4. high viscosity hyaluronic acid sodium gel according to any one of claim 1 to 3, it is characterised in that：
The high viscosity hyaluronic acid sodium gel also includes osmotic pressure regulator, and the osmotic pressure regulator is oozed the gel
Pressure is adjusted to 250～350mOsmol L thoroughly-1.
5. high viscosity hyaluronic acid sodium gel according to claim 4, it is characterised in that：
The osmotic pressure regulator is sodium chloride.
6. high viscosity hyaluronic acid sodium gel according to any one of claim 1 to 3, it is characterised in that：
The high viscosity hyaluronic acid sodium gel also includes pH value regulator, and the pH value of the gel is adjusted by the pH value regulator
Save to 6.8～7.8.
7. high viscosity hyaluronic acid sodium gel according to claim 6, it is characterised in that：
The pH value regulator is that disodium hydrogen phosphate/sodium dihydrogen phosphate buffering is right.
8. a kind of preparation method of high viscosity hyaluronic acid sodium gel according to any one of claim 1 to 3, which includes
Following steps：
1) according to formula in consumption weigh various components；
2) anionic surfactant, rheology control agent, glycerine are added in water for injection, are carried out after being completely dissolved degerming
Filter and high pressure steam sterilization, obtain gel carrier；
3) by step 2) in obtain gel carrier cooling, under clean environment, in the gel carrier add hyaluronic acid
Sodium is simultaneously stirred, until Sodium Hyaluronate is completely dissolved, obtains high viscosity hyaluronic acid sodium gel.
9. preparation method according to claim 8, it is characterised in that：
Step 2) described in aseptic filtration completed using sterilized 0.22 μm of filter core；The temperature of the high pressure steam sterilization is
121 DEG C, the time is 30 minutes.
10. preparation method according to claim 8, it is characterised in that：
Step 3) described in cool down after temperature be 40～60 DEG C；The cleanliness factor of the clean environment is more than hundred grades；Described stir
Mix and completed using agitator tank, mixing speed is in below 200rpm.
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| CN108261562A (en) * | 2017-08-11 | 2018-07-10 | 上海建华精细生物制品有限公司 | A kind of Sodium Hyaluronate skin sparing film and its preparation method and application |
| WO2023141614A1 (en) * | 2022-01-24 | 2023-07-27 | The Procter & Gamble Company | Skin care composition containing sodium hyaluronate and method of making the same |
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| CN101703454A (en) * | 2009-11-03 | 2010-05-12 | 广东名臣有限公司 | Washing-off type skin cleaning and nursing composite |
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Cited By (2)
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| CN108261562A (en) * | 2017-08-11 | 2018-07-10 | 上海建华精细生物制品有限公司 | A kind of Sodium Hyaluronate skin sparing film and its preparation method and application |
| WO2023141614A1 (en) * | 2022-01-24 | 2023-07-27 | The Procter & Gamble Company | Skin care composition containing sodium hyaluronate and method of making the same |
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Application publication date: 20170315 |