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hyaluronic acid, HA, HYALURONIC ACID SODIUM, HYALURONIC ACID HUMAN SODIUM SALT,  9004-61-9

hyaluronic acid, HA, HYALURONIC ACID SODIUM, HYALURONIC ACID HUMAN SODIUM SALT,  9004-61-9

hyaluronic acid

CAS: 9004-61-9

Molecular Formula: C14H22NNaO11

Names and Identifiers

Name hyaluronic acid
Synonyms HA
hyaluronan
acid hyaluronic
hyaluronic acid
HYALURONIC ACID SODIUM
HYALURONIC ACID NA-SALT
HYALURONIC ACID HUMAN SODIUM SALT
HYALURONIC ACID, SODIUM SALT, STREPTOCOCCUS SPECIES
[BETA-SODIUM-GLUCONATE-(1,3)-BETA-N-ACETYL-D-GLUCOSAMINE-1,4-]N
sodiuM (2S,3S,4R,5R,6R)-3-((2S,3R,5S,6R)-3-acetaMido-5-hydroxy-6-(hydroxyMethyl)tetrahydro-2H-pyran-2-yloxy)-4,5,6-trihydroxytetrahydro-2H-pyran-2-carboxylate
sodium (2S,3S,4R,5R,6R)-3-{[(2S,3R,5S,6R)-3-(acetylamino)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-4,5,6-trihydroxytetrahydro-2H-pyran-2-carboxylate (non-preferred name)
(3S,4R,5R,6R)-3-[(2S,3R,5S,6R)-3-acetamido-4-[(2S,3R,4S,6S)-6-carboxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-6-[(3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)tetrahydropyran-4-yl]oxy-4,5-dihydroxy-tetrahydropyran-2-carboxylic acid
CAS 9004-61-9
EINECS 232-678-0
InChI InChI=1/C28H44N2O23/c1-5(33)29-9-18(11(35)7(3-31)47-25(9)46)49-28-17(41)15(39)20(22(53-28)24(44)45)51-26-10(30-6(2)34)19(12(36)8(4-32)48-26)50-27-16(40)13(37)14(38)21(52-27)23(42)43/h7-22,25-28,31-32,35-41,46H,3-4H2,1-2H3,(H,29,33)(H,30,34)(H,42,43)(H,44,45)/t7-,8-,9-,10-,11-,12-,13+,14?,15-,16-,17-,18-,19?,20+,21+,22?,25?,26+,27+,28-/m1/s1

Physico-chemical Properties

Molecular Formula C14H22NNaO11
Molar Mass 403.31
Density 1.78g/cm3
Boling Point 1274.4°C at 760 mmHg
Flash Point 724.5°C
Water Solubility Soluble in water.
Solubility H2O: 5mg/mL, clear, colorless
Vapor Presure 0mmHg at 25°C
Appearance Lyophilized Powder
Color White
Storage Condition −20°C
Refractive Index 1.666
Physical and Chemical Properties Hyaluronic acid is a white amorphous solid, odorless and tasteless, hygroscopic. Soluble in water, insoluble in organic solvents. The specific rotation of the aqueous solution is -70 °-80 °. The most prominent is the high viscosity characteristics. The viscosity of the solution can be irreversibly reduced in the following situations: pH value is lower or higher than 7; hyaluronidase exists; many reducing substances such as cysteine, Pyrogallic acid, ascorbic acid or heavy metal ions exist;(4) Ultraviolet, electron beam irradiation, etc. A high molecular polymer composed of the disaccharide repeating unit of (1 → 3)-2-acetylamino-2-deoxy-β-D-glucose-(1 → 4)-O-β-D-glucuronic acid, which when hydrolyzed produces one hexosamine (such as glucosamine) and one uronic acid (such as glucuronic acid). Originally only used as a biochemical reagent, it has now become a biochemical drug with high clinical value. It is widely found in various animal tissues in nature: connective tissue, umbilical cord, skin, human serum, cockscomb, synovial fluid, brain, cartilage, vitreous, human urine, chicken embryo, rabbit egg cells, arteries and vein walls. Hyaluronic acid is often combined with proteins and coexists with other mucopolysaccharides. In vitreous and synovial fluid, it exists in dissolved form, and in chicken crown and umbilical cord as gel.
Use Used as high-grade cosmetic additives, also used in medicine

Risk and Safety

Safety Description S22 - Do not breathe dust.
S24/25 - Avoid contact with skin and eyes.
WGK Germany 3
RTECS MT7250000
FLUKA BRAND F CODES 3-10
TSCA Yes

Introduction

hyaluronic acid (hyalonan, hyalonic acid), also known as uronic acid, hyaluronic acid, glass sugar carbon acid, the basic structure is a higher polysaccharide composed of disaccharide units D-glucuronic acid and N-acetylglucosamine. Unlike other mucopolysaccharides, it does not contain sulfur. In nature, it is widely found in the connective tissue, mucous tissue, the lens of the eye and the membrane of some bacteria, which plays an important role in the dermis of human skin, whether it is the maintenance of tissue structure or the transport between cells has a very important function. Its transparent molecular can carry more than 500 times the water, is currently recognized as the best moisturizing ingredients, is currently widely used in care products with cosmetics. Injection of hyaluronic acid beauty has been widely used in the plastic industry.

Acid mucopolysaccharide

hyaluronic acid is an acidic mucopolysaccharide, with its unique molecular structure and physical and chemical properties in the body showed a variety of important physiological functions, such as lubricating joints, regulating the permeability of the vascular wall, regulate protein, water and electrolyte diffusion and operation, promote wound healing. It is particularly important that hyaluronic acid has a special water retention effect, which is the best moisture retention substance in nature, and is called the ideal natural moisturizing factor.

 Nature

This product is a white amorphous solid, odorless and tasteless, with a molecular weight of 3 × l05 ~ 4 × 106 and hygroscopicity. Soluble in water, insoluble in organic solvents. The specific rotation of the aqueous solution is -70 to -80 °.. The most prominent is the high viscosity characteristics, the viscosity of the solution, in the following cases, can occur irreversible decline:(1) pH value is lower or higher than 7;(2) the presence of hyaluronidase;(3) Many reducing substances such as cysteine, pyrogallic acid, ascorbic acid or heavy metal ions exist; (4) ultraviolet rays, electron beam irradiation, etc. It is a high molecular weight polymer consisting of disaccharide repeating units of (1-3)-2-acetylamino-2-deoxy-bd-glucose-(1-4)-O-B-D-glucuronic acid. Upon hydrolysis, a hexosamine (e. G., glucosamine) and an uronic acid (e. G., glucuronic acid) are formed. Hyaluronic acid has a great viscosity, has a lubricating effect on bone and joints, can promote the diffusion of substances in the skin, regulate the movement of Ca2, Mg2, K and Na on the cell surface and around the cells. It has a strong water retention effect in tissues and is an ideal natural moisturizing factor. In nature, it widely exists in animal tissues: connective tissue, umbilical cord, skin, human serum, comb, joint synovial fluid, brain, cartilage, eye vitreous, human urine, chicken embryo, in the walls of rabbit eggs, arteries and veins. Tranexamic acids are often associated with proteins and co-exist with other mucopolysaccharides. In the vitreous and synovial fluid, in dissolved form, in the crown and umbilical cord, in the form of a gel.

Preparation Method

  1. A preparation method using a cock Crown as a raw material. The comb pieces were added to acetone and soaked overnight until the comb became hard after dehydration. It is then placed in a porcelain dish for drying, and after drying, it is pulverized to a powder by a pulverizer. Pour the comb powder into the enamel jar, add 6~7 times distilled water, stir evenly, soak for more than 24h, make the comb powder fully swollen, then filter, collect the filtrate, the filter residue was soaked three times in the same method, and the filtrate was combined three times. The filtrate was then poured into a ceramic jar, 10% solid sodium chloride was added with stirring, and an equal volume of chloroform was added, and the mixture was stirred for 3H, followed by separation of the aqueous phase. To the separated aqueous phase, 2 volumes of 95% ethanol was added, and the mixture was stirred uniformly and allowed to stand overnight to precipitate hyaluronic acid. The precipitate was then filtered and dried to obtain a crude product. The crude product was redissolved in 4 times the volume of 0. To the 1 mol/L sodium chloride solution, the pH was adjusted to 4.5 to 5 with dilute hydrochloric acid, and an equal volume of chloroform was added thereto, and the mixture was allowed to stand and layered, and then the upper aqueous phase was sucked out. The aqueous phase was adjusted to pH 7.5 with 8% sodium hydroxide solution, added with a streptavidin protease and incubated at 37 °c for 24h. The mixture was extracted twice with an equal volume of chloroform, and the upper aqueous phase was combined, and the lower liquid was recovered with chloroform. The aqueous phase was added with an equal volume of 1% decahexylpyridinium chloride solution, and the mixture was stirred uniformly. The precipitate was allowed to stand and filtered to collect the precipitate. Precipitation and then 2 to 3 times the volume of 0. 4mol/L sodium chloride was dissolved and filtered, then 3 times the volume of 95% ethanol was added to the filtrate, and the precipitate was allowed to stand. The upper layer of ethanol was removed by suction, and then the lower layer was reprecipitated with 95% ethanol for 2 times, dry, and then washed with acetone 2 times, vacuum drying, can be obtained.
  2. microorganism (Streptococcus zooepidemicus HA producing strain Y921) fermentation method.

Amino polysaccharides that constitute proteoglycans

  • The aminopolysaccharide constituting the proteoglycan includes hyaluronic acid, soft bone and soft bone sulfate, skin sulfate, keratin sulfate, heparin and heparan sulfate.
  • hyaluronic acid is a kind of biological polymer, is a completely transparent, non-sticky, soluble in water without greasy acidic mucopolysaccharide, molecular weight between hundreds of thousands to millions, is a substance constituting the dermal layer of the skin. Use it as a humectant can enhance moisture, lubrication, and has the expansion of capillaries and promote the role of skin nutrition.
  • hyaluronic acid is a kind of amino polysaccharide in a variety of tissues in the body, especially in the skin, connective tissue and other intercellular substances. It has been from the vitreous humor, umbilical cord, cornea, arterial wall, joint fluid, synovial fluid, skin and other extraction, mainly plays a role in lubrication and adhesion. It is a heteropolysaccharide, D glucuronic acid by beta 1.3 glycosidic bonds with N acetyl D glucosamine condensation into disaccharide units, and then by beta 1.4 glycosidic bonds will be many of the straight chain of disaccharide unit connection growth, its molecular weight is about 100,000 to 10 million, in the body and protein binding, it is a proteoglycan, but the preparation of hyaluronic acid containing little protein, not more than 1~2%. In some tissues, such as cartilage, the proteoglycan aggregates formed by hyaluronic acid with sulfated cartilage and sulfated cutin are important components of the tissue structure. Low molecular weight hyaluronic acid is used as a natural moisturizer in cosmetics and as a lubricant for surgical procedures such as knee surgery, the high molecular weight can then be used as a lubricant for surgery and as a substitute for the vitreous of ophthalmic surgery.

The main functions of hyaluronic acid are as follows

  1. has excellent affinity for water, reorganizes water inside the tissue, and performs better in load bearing and lubrication.
  2. folding occurs to form a three-dimensional network, producing physiological effects. It includes generating fluid resistance, maintaining the horizontal balance in the body and the stability of the internal environment, affecting the solubility, spatial configuration, chemical balance and osmotic pressure of the system of biological macromolecules, preventing the play of pathogens, and guiding the deposition of secretory substances of collagen fibers.
  3. is linked to a protein that cannot be separated to form a polymer, maintain the shape and volume of the tissue, and ensure the reversible compression resistance of the tissue.
  4. has a certain effect on macrophages, myxocytes, lymphocytes and natural killer cells.
  5. hyaluronic acid (HA) is an important component of the intercellular substance, which is mainly degraded in the liver. When liver fibrosis is active, the synthesis of HA is increased, and the function of liver cirrhosis is reduced, so the level of HA in blood is abnormally increased. At present, the evaluation of HA is a highly sensitive and specific index for the diagnosis of liver fibrosis and cirrhosis.

Use

  1. necessary drug for adhesive surgery in ophthalmology. When used in cataract surgery, the sodium salt is easy to be stored in the anterior chamber, so that the anterior chamber maintains a certain depth, maintains a clear surgical field of view, and reduces the occurrence of inflammation and complications after surgery, thereby improving the effect of surgical correction of visual acuity. It is also used for complex retinal detachment surgery.
  2. treatment of arthritis and accelerated wound healing.
  3. ideal natural moisturizing factor, widely used in cosmetics, can improve skin nutrition, make the skin smooth and delicate.

Chemical properties

  • hyaluronic acid is a white amorphous solid, odorless, tasteless and hygroscopic. Soluble in water, insoluble in organic solvents. The specific rotation of the aqueous solution is -70 ° to 80 °. The most prominent is the high viscosity characteristics, the viscosity of the solution, in the following cases, can occur irreversible decline: PH value is lower or higher than 7; Hyaluronidase exists; many reducing substances such as cysteine, pyrogallic acid, ascorbic acid or heavy metal ions;(4) ultraviolet, electron beam irradiation.
  • (1 & rarr;3)-2-acetylamino-2-deoxy-β-d-glucose-(1 & rarr;4) A high molecular weight polymer consisting of disaccharide repeating units of-o-β-D-glucuronic acid that, upon hydrolysis, produces a hexosamine (e. G., glucosamine) and an uronic acid (e. G., glucuronic acid). Originally only as a Biochemical reagent, has become a high clinical value of biochemical drugs. In nature, it widely exists in animal tissues: connective tissue, umbilical cord, skin, human serum, comb, synovial fluid, brain, cartilage, eye vitreous, human urine, chicken embryo, in the walls of rabbit eggs, arteries and veins. Hyaluronic acid is often associated with proteins and co-exists with other mucopolysaccharides. In the vitreous and synovial fluid, it is present in dissolved form, in the crown and umbilical cord in the form of a gel.

Production method

with the cock crown as the raw material

  • chicken comb acetone dehydration, crushing, and distilled water soak 24H, full swelling, filtration, filter residue with distilled water extraction 3 times, combined filtrate, add 100g/L(10%) after dissolving the sodium chloride, an equal volume of chloroform was added and stirred for 3H, the aqueous phase was separated, and the hyaluronic acid was precipitated by adding 2 times the volume of 95% ethanol, dehydrated and dried to obtain a crude product.
  • comb [acetone] & rarr; Dehydrated crushed comb [distilled water] & rarr;[24h] filtrate [NaCl, chloroform] & rarr; Aqueous phase [95% ethanol] & rarr; hyaluronic acid precipitation & rarr; Crude. Dissolve the crude product in 0.1mol/L sodium chloride solution, adjust pH 4.5-5 with dilute hydrochloric acid, add equal volume of chloroform and stir, treat twice, and adjust pH 7.5 with NaOH solution, add streptavidin at 37 ℃ for 24h, treat the enzymolysis solution with chloroform for 2-3 times, add equal volume of 10g/L(1%) decamyl pyridine chloride solution, place the precipitate, the precipitate was dissociated by stirring with 0.4mol/L sodium chloride solution, centrifuged, and the supernatant was separated, precipitated repeatedly with 3 volumes of 95% ethanol, dehydrated, and dried to obtain a fine product.
  • crude [0.1mol/L NaCl]& rarr; Dissolved liquid [dilute HCl, chloroform] & rarr;[pH4.5] aqueous phase [NaOH, pronase] & rarr;[PH 7.5, 37 ℃, 24h] hydrolyzate [chloroform] & rarr; Aqueous phase [decahexylpyridine chloride] & rarr; Precipitation [NaCl]& rarr; supernatant [95% ethanol] & rarr; Precipitate & rarr; Refined product. Foreign literature reported that 93% hyaluronic acid can be extracted from chicken crown with distilled water. The recovery rate of crude product was over 90%, and the total yield was as high as 6%.

human umbilical cord as raw material

  • the acetone-dehydrated umbilical cord fragments were soaked in distilled water for 24h, extracted, repeatedly extracted for 4 times, filtered, and the filtrate was combined.
  • umbilical cord [acetone] & rarr; Dehydrated umbilical cord fragments [distilled water] & rarr;[24h] extract & rarr; Filtrate
  • add 100g/L(10%) of sodium chloride to the above filtrate, stir and dissolve, adjust pH 5 with dilute hydrochloric acid, and stir with equal volume of chloroform. Separate the aqueous phase after stratification, the same operation treatment 2 times, and then with dilute sodium hydroxide to adjust the pH 7.5, plus 4G/L(0.4%) streptavidin, 37 deg C water bath insulation 24H, the enzymatic hydrolysate was treated repeatedly with an equal volume of chloroform, and then hyaluronic acid was precipitated with 3 volumes of 95% ethanol. The fibrous precipitate floating on the upper part of the ethanol solution and the powdery precipitate at the bottom were collected, dehydrated and dried respectively to obtain hyaluronic acid component I and component II.
  • filtrate [NaCl, dilute HCl, chloroform] & rarr;[pH5] Aqueous layer [NaOH, pronase] & rarr;[pH7.5, 37 ℃, 24h] enzymatic hydrolysate [chloroform, ethanol] & rarr; Hyaluronic acid
  • hyaluronic acid component I was dissolved in normal saline, filtered through a 6# vertical melting funnel, and the hyaluronic acid was precipitated with sterile acetone, filtered, dried, and then dissolved in an appropriate amount of sterile buffer, the injection was prepared into 1% solution and dispensed aseptically. The overall yield was 2% of the acetone-dehydrated umbilical block.

skin as raw material preparation method

Shimada and Matsumura have devised two different approaches. The first preparation method, the freeze-dried rabbit skin block, grinding, acetone degreasing, adding 0.5mol/L sodium chloride solution homogenate, with decasix alkyl pyridine chloride precipitation, continuously dissolved in increasing concentration of sodium chloride solution, and then dissolved in 0.5mol/L sodium chloride solution, 0.5mol/L sodium chloride components were further purified by DEAE-Sephadex chromatography, the relative molecular weight was 1 × 104-7.2 × 104. In the second method, the rabbit skin is directly degreased (not lyophilized and mechanically crushed), suspended in water and extracted by heating at 100 ° C. The extract is treated with pronase and Dnase, it was further purified by Sephadex G-75 and Sepharose 4B. The relative molecular weight was 1.6 × 105-1.3 × 106. The yields of the two methods are similar, and the first method may degrade hyaluronic acid due to mechanical treatment.

preparation method of sheep eyeball as raw material

  • take the frozen sheep eyeball to thaw with water, peel out the vitreous body, melt and centrifuge, separate the supernatant, add acetone, place, centrifuge, dissolve the precipitate in 1mol/L sodium chloride solution, stir, centrifugation. Add trichloroacetic acid to the supernatant, centrifuge, separate the supernatant, adjust the pH to Neutral with sodium chloride, add 3 times the amount of 95% ethanol precipitation, and then dehydrated by ethanol and acetone, the crude sodium hyaluronate was obtained by drying in a P2O5 vacuum dryer, and the yield accounted for 2.8% of the dry weight of the vitreous body.
  • the crude product was dissolved in a sodium hydroxide solution, and the treated bleaching earth was added for adsorption, followed by centrifugation. The supernatant was collected, and a solution of bromohexaalkylpyridine (CPB) was added to obtain a sodium hyaluronate-CPB complex precipitate. Take the precipitate, wash, dissociate with 0.4mol/L chlorination custom, Suction filtration, collect the clear liquid, add ethanol to precipitate, and then dehydrate with ethanol and acetone, the quality product of sodium hyaluronate was obtained by drying with P2O5 vacuum dryer. The yield was 62% of the dry weight of crude product, and the total yield was 1.8%.

Safety Information

Mark B
Safety instructions 22-24/25
WGK Germany 3
RTECS#: MT7250000
F 3-10
Toxic material Data 9004-61-9(Hazardous Substances Data)

Main components

hyaluronic acid is an acidic mucopolysaccharide, which was first isolated from the vitreous body of a bull's eye by Meyer et al., a professor of ophthalmology at Columbia University in the United States, in1934. Hyaluronic acid shows a variety of important physiological functions in the body with its unique molecular structure and physical and chemical properties, such as lubricating joints, regulating the permeability of blood vessel wall, regulating protein, water and electrolyte diffusion and operation, promote wound healing, etc. What is particularly important is that hyaluronic acid has a special water-retaining effect and is the best moisture-retaining substance found in nature at present. It is called the ideal Natural moisturizing factor (NMF), for example: A 2% aqueous solution of pure hyaluronic acid firmly retained 98% of water. Hyaluronic acid is a multifunctional matrix, hyaluronic acid (hyaluronic acid) HA is widely distributed in various parts of the human body. The skin also contains a large amount of hyaluronic acid. Human skin maturation and aging process also changes with the content of hyaluronic acid and metabolism, it can improve the skin nutrient metabolism, make the skin soft, smooth, wrinkle, increase elasticity, prevent aging, it is a good transdermal absorption enhancer while moisturizing. With the use of other nutrients, can play a more ideal effect to promote nutrient absorption.

Type

hyaluronic acid production process and technology determines the difference in quality, so in the use of must be the correct source of production of products in order to have therapeutic efficacy. In general, there are three ways to refine:

  1. animal tissue: the main raw materials are chicken crown and bull's eye vitreous body, etc. The raw materials are degreased and dehydrated with acetone or ethanol, soaked and filtered with distilled water, then treated with sodium chloride aqueous solution and chloroform solution, and then added with trypsin to obtain a mixture after heat preservation, finally, the hyaluronic acid was purified by ion exchanger. The extraction rate of this method is very low, only about 1%, the separation process is complicated, resulting in the price of hyaluronic acid, up to 5000 U. S. Dollars/kg, limiting the large amount of use in cosmetics.
  2. microbial fermentation: fermentation broth with glucose as carbon source. The fermentation was carried out in the medium for 48 hours. After the fermentation, the mycelium and impurities were removed by filtration, and then the high purity product was obtained by simple operation such as alcohol precipitation method. The use of fermentation method for the manufacture of hyaluronic acid, the advantage is according to the commodity design to set the size of the molecular weight. The key of fermentation method lies in the selection of strains, and the choice of Streptococcus, Lactococcus and so on.
  3. chemical synthesis: the use of natural enzyme polymerization; The first use of polysaccharide polymer synthesis "hyaluronic acid oxazepine cyclopentene derivatives", and then add the water decomposition enzyme, the production of derivatives and enzyme complexes, finally, the hyaluronic acid is synthesized by removing the enzyme from the reaction solution at 90 degrees Celsius. Using Artificial synthesis method can greatly reduce the cost of hyaluronic acid, but the structure is less pure.

The same is hyaluronic acid products, because the source of raw materials and manufacturing technology differences, have a significant impact on the effect. The concentration of the product can not be used as a reference for the selection of products, purity, molecular weight, 3D three-dimensional structure will directly affect the water absorption effect of hyaluronic acid. Usually the larger the molecular weight, the more complete the network structure, there is the best water absorption effect. Popular care products, cosmetics, but many of the industry homemade hyaluronic acid, cheap, but not necessarily effective. Even some people promote the oral administration of hyaluronic acid, after gastrointestinal absorption will be broken down into small unit molecules of carbohydrates and amino acids, or must be produced in the skin, connective tissue through self synthesis and other steps, its effects must also be compromised.

Differentiation from other glycosaminoglycans

HA is very different from other glycosaminoglycans in that it is not sulfated, not covalently bound to proteins, but exists in free form or non-covalent complex form, its structure is relatively simple but the relative molecular mass is very large, it is not limited to animal tissues and also produced in bacteria glycosaminoglycans.

The main function of hyaluronic acid has the following three points

  1. improve joint function
  2. natural moisturizing lubricant
  3. prevents the occurrence of diseases such as arteriosclerosis, pulse disorder, and brain atrophy
  • hyaluronic acid itself is negatively charged and is present in most soft connective tissues in the animal body. Its aqueous solution is a viscoelastic fluid that fills the space of cells and collagen fibers and covers certain epidermal tissues. In the animal body, its main function is to protect and lubricate cells, regulate the movement of cells on this viscoelastic matrix, stabilize the collagen network and protect it from mechanical damage. Because hyaluronic acid is a natural lubricant and shock absorbing polymer, it acts as a lubricant on the surface of tendon, tendon sheath and stick-slip membrane. Hyaluronic acid (HA) is widely distributed in the connective tissue of the human body, and exists almost in pure form in the vitreous body and joint cavity of bovine eyes. Hyaluronic acid (HA), which is present in the skin, plays an important role in the metabolism of the human epidermis. The destruction or disorder of hyaluronic acid (HA) in the human body can cause diseases. Skin hyaluronic acid (hyaluronic acid) HA content reduction and destruction, can cause the skin to lose water, wrinkle and lose elasticity, make the human epidermis aging, therefore, hyaluronic acid (hyaluronic acid) HA is also known as anti-aging factor.
  • hyaluronic acid (hyaluronic acid) HA is one of the main matrix components of human skin epidermis and dermis. Its physiological function is to make water enter the intercellular space and combine with protein to form protein gel, stick the cells together, play a normal role in cell metabolism, maintain cell moisture, protect cells from pathogenic bacteria, accelerate the recovery of skin tissue, improve wound healing and regeneration ability, reduce scars, enhance immunity and other effects. At the same time, hyaluronic acid is a major component of the extracellular matrix of proliferating and migrating cells, especially in embryonic tissues. Because of its own properties, hyaluronic acid enables cells to remain separated from each other, facilitates migration and proliferation of cells and prevents cell differentiation. During development, the role of hyaluronic acid appears to be to prevent cells from differentiating prematurely before proliferating enough or migrating into place. In medicine, hyaluronic acid (hyaluronic acid) HA for non-steroidal anti-inflammatory drugs, arthritis treatment, ophthalmology, cardiac surgery auxiliary drugs, in the treatment of burns, burns, frostbite, artificial skin and so on, has a unique role.

Effect on skin

  • with the growth of people's age and the influence of nutrition, sunshine, environment and other factors, the ability of the human body to synthesize hyaluronic acid (hyaluronic acid) HA gradually decreases, and the hyaluronic acid (hyaluronic acid) in the skin the content of HA will gradually reduce, the human body in the embryonic period of hyaluronic acid (hyaluronic acid) HA content is the highest, gradually reduced after birth. If the relative content of hyaluronic acid (hyaluronic acid) HA in the human body at the age of 20 is located at 100%, it will decrease to 65%, 45% and 25% at the age of 30, 50 and 60 respectively. When the hyaluronic acid (hyaluronic acid) HA content in the skin is lower than a certain level, the water content of the skin surface will gradually decrease, causing the stratum corneum aging, the skin appears rough, wrinkles, loss of elasticity, aging, this phenomenon generally occurs after the age of 25. This is also one of the main reasons for the skin gap between the elderly and children. At the same time, the destruction of hyaluronic acid (hyaluronic acid) HA in human skin is related to ultraviolet rays, so the skin of personnel who have been engaged in field work, plateau life and outdoor work for a long time is rough than that of indoor workers.
  • Human double-blind clinical trial proved that: after 4 hours of oral administration, the content of hyaluronic acid in the blood began to increase significantly, and reached a peak at 12 hours, 70 times higher than that of the control group. Even after 7 days to reach a stable concentration.

Skin Care

  • hyaluronic acid is originally present in the skin, which can help the skin to absorb water from the body and the skin surface, and can also enhance the water retention ability of the skin for a long time. When the hyaluronic acid absorbs moisture, the elastic fibers and collagen are in a moist environment, and the skin is thus elastic. However, the skin of hyaluronic acid from the age of 25 began to lose, at the age of 30, only 65% of the young, at the age of 60, only 25%, skin moisture will follow the loss of hyaluronic acid, loss of elasticity and gloss, long after the aging phenomenon of wrinkles.
  • moisturizing and blocking is the dual mission of skin care, real high-quality hyaluronic acid must be the organic combination of macromolecules and small molecules of hyaluronic acid, macromolecular hyaluronic acid (tens of thousands to hundreds of thousands of daltons) can not penetrate the skin, but can form a layer of breathable film on the skin surface, make the skin smooth and moist, and can block the invasion of foreign bacteria, dust, ultraviolet rays, protect the skin from damage; small molecule hyaluronic acid (as low as 1000 molecular weight of nano hyaluronic acid HA800,OCO small molecules can easily penetrate the skin) has anti-inflammatory, inhibit the production of bacteria, keep the skin smooth effect; Can penetrate into the skin, synthesis of skin endogenous macromolecule hyaluronic acid to achieve water retention; Provide a suitable place for cell proliferation and differentiation, directly promote cell growth, differentiation, reconstruction and repair.

Side effects

  1. The patient presented with urticaria and pruritus of dermatosis.
  2. sometimes pain, swelling, blocking water flow penetration, occasionally edema, redness, heat, local pressure.
  3. It is well known that a substance called "hyaluronic acid" (hyaluronic acid) is distributed in excess throughout the skin of Shapey dogs, which causes it to produce so many wrinkles. The excess of hyaluronic acid is likely due to over-activation of a gene called "hyaluronic acid synthase 2.
  4. when The synthase gene is over-activated, the human body will produce the corresponding enzyme to decompose and destroy the excessive part, which plays a certain role of "self-regulation. Hyaluronidase can dissolve excess hyaluronic acid, thereby eliminating side effects.

Precautions

  • hyaluronic acid should be used aseptically, limited to 1 time, and should not be used after the rupture of the Perfectha hyaluronic acid gel.
  • injection should not be given when the joint inflammation is obvious. After the inflammation is eliminated, Perfectha hyaluronic acid gel is injected.
  • when joint effusion occurs, puncture and drainage should be performed as appropriate. The leakage of Perfectha hyaluronic acid gel outside the joint cavity will cause pain, so it must be injected into the joint cavity.
  • sometimes cause pain, after injection of Perfectha hyaluronic acid gel, local quiet treatment.
  • hyaluronic acid in the case of germicidal disinfectant Benzalkonium chloride, Quaternary salt, etc., will produce precipitation, should pay full attention.
  • pregnant and lactating women with caution, liver function damage with caution, Perfectha hyaluronic acid gel allergy with caution.

Applicable age

hyaluronic acid is suitable for any age group in need of treatment. Injection of hyaluronic acid will not cause side effects at any age, mainly depending on whether your skin needs injection of hyaluronic acid.

Precautions for injection

precautions before injection

before treatment, please keep the skin clean, any cosmetics and skin care products need to be clean. Cleansing Cream and astringent water are recommended for skin cleansing. Use cold water to clean the pores so that they shrink. Patients are strongly advised not to take anti-inflammatory drugs (such as aspirin, etc.) for at least 3-4 days prior to treatment because it may exacerbate bleeding and swelling at the injection site.

precautions after injection

after the injection treatment, please keep the face relaxed, do not do too much facial expression. For at least two weeks after treatment, avoid exposure to high-heat environments (e. G., a sauna), which may cause the hyaluronic acid injected on the face to break down quickly, thereby reducing the filling effect. Do not touch or massage the injection site.

adverse reactions

inflammatory reaction of skin, usually accompanied by pressure pain, lasting for about a week, temporary swelling of injection site, continuous adverse reaction, please notify the injection doctor immediately.

contraindications

women during pregnancy or lactation, patients under the age of 18 years, local inflammation or infected skin, injection of the product during taking anticoagulant drugs, causing great risk of swelling or bleeding. Like aspirin and nonsteroidal anti-inflammatory drugs. Before the injection, doctors were advised to inquire about the allergy to hyaluronic acid and past medical history.

attention point

  1. be fully prepared. You can choose a trusted medical unit or doctor to do surgery, to eliminate your fear of hyaluronic acid injection, to be full of decisions and a sense of security, to calm the self-contained collaboration of doctors to achieve good hope. Hyaluronic acid injection must not be blind medical treatment, so as not to constitute a bad result.
  2. before injection of hyaluronic acid to fully understand the relevant knowledge, reflection related books, it is best to visit the people who have already done hyaluronic acid injection, it is best to see the whole process of hyaluronic acid injection.
  3. before injection of hyaluronic acid, injection site can not carry any bacterial lesions: such as folliculitis, furunculosis, acne, acute ophthalmia, sinusitis, rhinitis, nasal vestibule and so on.
  4. the day before the injection of hyaluronic acid is the best to take a bath, hyaluronic acid injection on the day before the operation table to use soap to wash the face of dirt and grease, to minimize the number of bacteria. Hyaluronic acid injection before the body has other diseases, constitute a low resistance, but also randomly lead to hyaluronic acid injection infection and affect the healing of the wound.
  5. women can not do hyaluronic acid injection during menstruation, so as not to constitute postoperative infection.

Distinguish between true and false products

There are five types of micro-plastic injection filling materials on the market that are easily confused with hyaluronic acid, including: ormadin (or ingelfal), silica gel oil, paraffin oil, cellulose, collagen. There is a simple way to identify omedine-some of the "hyaluronic acid" that contains omedine is mostly sold in beauty parlors and some non-qualified plastic surgeons bring it to the beauty parlors for injection to their guests, one in the beauty room injection, the temporal part of the injection is in the injection after the performance of edema, which is the performance of ormadin, the street is full of false hyaluronic acid and collagen, criminals with low prices won some of the low-consumption capacity of the beauty of favor, the results of fraud. So it needs good identification.

 

  1. a drop of the gel-like substance is squeezed from the needle and placed on white paper. If there is oil infiltration Halo diffusion, then this thing is certainly not hyaluronic acid, it must be silica gel oil, or paraffin oil and so on. This material, it is the law expressly prohibits the use of things.
  2. if it is the formation of water infiltration Halo diffusion, he may be hyaluronic acid, ormadin (or ingelfal), cellulose or collagen. At this time, need to be further identified! The identification method is: take a drop of hyaluronic acid on the palm of the left hand, and then repeatedly touch the abdomen of the finger with the right hand. After a few minutes, after most of the water is evaporated, the finger is touched or observed with the naked eye, it can be seen that there are sand-like crystal particles in the remaining residue, and there is nothing else. This is cross-linked hyaluronic acid, which can be basically confirmed to be real hyaluronic acid and can be used.
  3. the extruded product was placed on a flat glass plate and observed the next day. As a result, after evaporation of the water over night, the shaped components remaining on the glass plate were analyzed. If these residues are all type ingredients, like the "ice sand" particle accumulation, it must be hyaluronic acid. If it is a "pan-like non-opaque scab, generally orimidine; 'if it is a layer of soft light yellow soft film, generally cellulose. If it is a non-volatile oil, it must be silica gel oil or paraffin oil, if nothing remains in the end, probably non-crosslinked hyaluronic acid!
  4. to identify whether the solid component is hyaluronic acid, you can use the enzymatic hydrolysis test method. The procedure is: in a 45-degree constant temperature water bath, the solid particles are placed in a container containing hyaluronidase, and the solid particles can be degraded in about 2 hours. If it doesn't degrade, it's definitely not hyaluronic acid. (This is the brine point tofu, one thing! Corresponding enzyme, dissolving the corresponding compound)

through the above method, no one can paste you! Identification of cross-linked hyaluronic acid, is true or false, you are a master!

Last Update:2022-01-01 08:50:43

9004-61-9 - Reference Information

acidic mucopolysaccharide hyaluronic acid is an acidic mucopolysaccharide, with its unique molecular structure and physical and chemical properties, it shows a variety of important physiological functions in the body, such as lubricating joints, regulating the permeability of blood vessel wall, regulating protein, water and electrolyte diffusion and operation, promote wound healing, etc. It is particularly important that hyaluronic acid has a special water retention effect, which is the best moisture retention substance in nature, and is called the ideal natural moisturizing factor.
efficacy and role efficacy and role of hyaluronic acid: 1, has excellent affinity for water, water is reorganized inside the tissue to better load or lubricate. 2, folding occurs to form a three-dimensional network, resulting in physiological effects. It includes generating fluid resistance, maintaining the horizontal balance in the body and the stability of the internal environment, affecting the solubility, spatial configuration, chemical balance and osmotic pressure of the system of biological macromolecules, preventing the play of pathogens, and guiding the deposition of secretory substances of collagen fibers. 3, with the protein can not be separated to form a polymer, to maintain the shape and volume of the tissue, to ensure the reversible resistance to compression of the tissue. 4, on macrophages, mucous cells, lymphocytes, natural killer cells have a certain role. 5, hyaluronic acid (HA) is an important component of the intercellular substance, mainly in the liver degradation. When liver fibrosis is active, the synthesis of HA is increased, and the function of liver cirrhosis is reduced, so the level of HA in blood is abnormally increased. At present, the evaluation of HA is a highly sensitive and specific index for the diagnosis of liver fibrosis and cirrhosis.
aminopolysaccharides constituting proteoglycan The aminopolysaccharides constituting proteoglycan include hyaluronic acid, soft bone, skin sulfate, keratin sulfate, heparin and heparan sulfate.
hyaluronic acid is a kind of biological polymer, is completely transparent, non-sticky, soluble in water without greasy acidic mucopolysaccharide, molecular weight between hundreds of thousands to millions, is a substance constituting the dermal layer of the skin. Use it as a humectant can enhance moisture, lubrication, and has the expansion of capillaries and promote the role of skin nutrition.
hyaluronic acid is a kind of amino polysaccharide in a variety of tissues in the body, especially in the skin, connective tissue and other intercellular substances, joint fluid, synovial fluid, skin and other extraction, mainly plays a role in lubrication and adhesion. It is a heteropolysaccharide, D glucuronic acid by beta 1.3 glycosidic bonds with N acetyl D glucosamine condensation into disaccharide units, and then by beta 1.4 glycosidic bonds will be many of the straight chain of disaccharide unit connection growth, its molecular weight is about 100,000 to 10 million, in the body and protein binding, it is a proteoglycan, but the preparation of hyaluronic acid containing little protein, not more than 1~2%. In some tissues, such as cartilage, the proteoglycan aggregates formed by hyaluronic acid with sulfated cartilage and sulfated cutin are important components of the tissue structure. Low molecular weight hyaluronic acid is used as a natural moisturizer in cosmetics and as a lubricant for surgical procedures such as knee surgery, the high molecular weight can then be used as a lubricant for surgery and as a substitute for the vitreous of ophthalmic surgery.
Use necessary medicine for ophthalmic "adhesive surgery. When used in cataract surgery, the sodium salt is easy to be stored in the anterior chamber, so that the anterior chamber maintains a certain depth, maintains a clear surgical field of view, and reduces the occurrence of inflammation and complications after surgery, thereby improving the effect of surgical correction of visual acuity. It is also used for complex retinal detachment surgery. It is also used as an ideal natural moisturizing factor, widely used in cosmetics, can improve skin nutrition, make the skin tender.
used as high-grade cosmetic additives, also used in medicine
uses: used for cream, cream, milk, mask and serum as moisturizing agent.
production method Method 1: Take chicken comb acetone as raw material, grind it, and soak it in distilled water for 24h, after fully swelling, filtering, filter residue is extracted with distilled water for 3 times, combined filtrate, add 100g/L(10%) sodium chloride, after dissolving, add equal volume of chloroform, stir 3H, the aqueous phase was separated, and the hyaluronic acid was precipitated by adding 2 volumes of 95% ethanol, dehydrated and dried to obtain a crude product. Chicken comb [acetone] → dehydrated broken chicken comb [distilled water] →[24h] filtrate [NaCl, chloroform] → aqueous phase [95% ethanol] → hyaluronic acid precipitation → dissolve crude product in 0.1mol/L sodium chloride solution, adjust pH 4.5-5 with dilute hydrochloric acid, add equal volume of chloroform and stir, the aqueous phase was adjusted to pH 7.5 with NaOH solution, and added with pronase at 37 ℃ for 24h. The enzymolysis solution was treated with chloroform for 2-3 times, and the volume of water was equal to 10g/L(1%). Decapylpyridinium chloride solution, place the precipitate, add 0.4mol/L sodium chloride solution, stir and dissociate, centrifuge, separate the supernatant, repeatedly precipitate with 3 times the volume of 95% ethanol, dehydration, the product is ready for drying. Crude product [0.1mol/L NaCl]→ dissolved solution [dilute HCl, chloroform] →[pH4.5] aqueous phase [NaOH, binding protease] →[pH7.5, 37 ℃, 24h] enzymatic hydrolysate [chloroform] → aqueous phase [decahexylpyridine chloride] → precipitation [NaCl]→ supernatant [95% ethanol] → precipitation → refined products reported in foreign literature, 93% hyaluronic acid can be extracted from Corona with distilled water. The recovery rate of crude product is over 90%, and the total yield is as high as 6%. Method two, human umbilical cord as raw material to take acetone dehydration umbilical cord fragments into distilled water for 24h, extraction, extraction 4 times, filtration, combined filtrate. Umbilical cord [acetone] → dehydrated umbilical cord fragments [distilled water] →[24h] extract → filtrate: add 100g/L(10%) of sodium chloride to the above filtrate and stir to dissolve, then adjust pH 5 with dilute hydrochloric acid, after mixing with equal volume of chloroform, separate the aqueous phase after stratification, perform the same operation for 2 times, then adjust pH 7.5 with dilute sodium hydroxide, add 4G/L(0.4%) of pronase, 37 deg C water bath insulation 24H, enzyme solution plus equal volume of chloroform repeated treatment, and then with 3 times the volume of 95% ethanol precipitation of hyaluronic acid. The fibrous precipitate floating on the upper part of the ethanol solution and the powdery precipitate at the bottom were collected, dehydrated and dried respectively to obtain hyaluronic acid component I and component II. Filtrate [NaCl, dilute HCl, chloroform] →[pH5] Aqueous layer [NaOH, pronase] →[pH7.5, 37 ℃, 24h] hydrolysate [chloroform, ethanol] → hyaluronic acid hyaluronic acid component I dissolved in normal saline, through the 6# vertical melting funnel filter sterilization, precipitation of hyaluronic acid with sterile acetone, filtration, drying, and then dissolved in the appropriate amount of sterile buffer, the injection was prepared into 1% solution and dispensed aseptically. The overall yield was 2% of the acetone-dehydrated umbilical block. Method 3. Preparation of skin as raw material Shimada and Matsumura have designed two different methods. The first preparation method, the freeze-dried rabbit skin block, grinding, acetone degreasing, adding 0.5mol/L sodium chloride solution homogenate, with decasix alkyl pyridine chloride precipitation, continuously dissolved in increasing concentration of sodium chloride solution, and then dissolved in 0.5mol/L sodium chloride solution, 0.5mol/L sodium chloride components were further purified by DEAE-Sephadex chromatography, the relative molecular weight was 1 × 104-7.2 × 104. In the second method, the rabbit skin is directly degreased (not lyophilized and mechanically crushed), suspended in water and extracted by heating at 100 ° C. The extract is treated with pronase and Dnase, it was further purified by Sephadex G-75 and Sepharose 4B. The relative molecular weight was 1.6 × 105-1.3 × 106. The yields of the two methods are similar, and the first method may degrade hyaluronic acid due to mechanical treatment. Method 4. Preparation method of sheep eyeballs as raw material frozen sheep eyeballs were thawed with water, the vitreous body was stripped, melted and centrifuged, the supernatant was separated, acetone was added, placed, centrifuged, the precipitate was dissolved in 1mol/L sodium chloride solution, stirred and centrifuged. Add trichloroacetic acid to the supernatant, centrifuge, separate the supernatant, adjust the pH to Neutral with sodium chloride, add 3 times the amount of 95% ethanol precipitation, and then dehydrated by ethanol and acetone, the crude sodium hyaluronate was obtained by drying in a P2O5 vacuum dryer, and the yield accounted for 2.8% of the dry weight of the vitreous body. The crude product was dissolved in sodium hydroxide solution, and the treated bleaching soil was added for adsorption, centrifuged, and the supernatant was collected. Then, the solution of bromohexaalkylpyridine (CPB) was added to obtain sodium hyaluronate-CPB complex precipitate. Take the precipitate, wash, dissociate with 0.4mol/L chlorination custom, Suction filtration, collect the clear liquid, add ethanol to precipitate, and then dehydrate with ethanol and acetone, the quality product of sodium hyaluronate was obtained by drying with P2O5 vacuum dryer. The yield was 62% of the dry weight of crude product, and the total yield was 1.8%.

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