ヒアルロン酸粉末の用途は何ですか?

ヒアルロン酸, also known as hyaluronic acid, is an acidic mucopolysaccharide that forms a viscoelastic substance when combined with water molecules [1]. Hyaluronic acid is mainly found in the skin and connective tissues of the human body, where it acts as an extracellular matrix for cellular insertion. In addition to providing a certain volume of extracellular matrix for the cells in the body, hyaluronic acid also influences the stability, binding and viscoelasticity of the tissues. のmolecular structure of all natural hyaluronic acids is the same, with virtually no species- or tissue-specific differences, so pure hyaluronic acid is not immunogenic [2].

Hyaluronic acid was first isolated from the vitreous body of the bovine eye by Meyer et al, Professor of Ophthalmology at Columbia University, USA, in 1934 [3]. Since Kendall et al. discovered that Streptococcus haemolyticus could produce hyaluronic acid in 1937, many scientists and scholars have been engaged in the study of hyaluronic acid production by microbial fermentation. In 1985, Shiseido of Japan first reported the production of hyaluronic acid by streptococcal fermentation. In 2003, the United States also approved a patent for the production of hyaluronic acid by fermentation [4].

Since then, there have been many studies on the selection and breeding of hyaluronic acid fermentation strains. For example, Fong et al. [5] obtained non-hemolytic and non-hyaluronidase-producing strains of Streptococcus zooepidemicus by mutagenicity with nitrosoguanidine. Up to now, the technology of hyaluronic acid production by microbial fermentation has been matured in foreign countries and has entered the industrialisation stage. In China, the production of hyaluronic acid by fermentation of Streptococcus faecalis has also become a research hotspot and has gradually entered into the industrialisation stage, and the development, production and application of hyaluronic acid has a very attractive prospect.

1ヒアルロン酸の物理的および化学的性質と生理学的機能

1.1物理的および化学的性質

ヒアルロン酸は水に溶け、その溶液はある負電荷を持つ酸性です。ヒアルロン酸の分子は、高分子polymerisation構成の多糖類されの二糖类ユニットをβ-D-glucuronic酸やβ-D-N-acetylglucosaminoglucose。

Hyaluronic acid is a major component of some bacterial pods such as Streptococcus and Pseudomonas aeruginosa. Unlike other mucopolysaccharides, hyaluronic acid is an acidic mucopolysaccharide and does not contain sulphur in its molecular structure. のspecific intermolecular configuration of hyaluronic acid gives it a high viscosity and moisturising effect. Hyaluronic acid molecules can carry about 500 times as much water as themselves, which is recognised as the best moisturising substance, and is therefore mass-produced and widely used in functional foods and cosmetics [6].

1.2な生体機能を

1.2.1保水機能:

Hyaluronic acid has strong water absorption and water retention. In higher concentration solution, hyaluronic acid has strong hydrophilicity, and its long molecular chains are interwoven in a grid shape, which are combined with water molecules through hydrogen bonding.

1.2.2红速保護:

The effect of hyaluronic acid on the skin depends on its molecular weight. Hyaluronic acid with large molecular weight is mainly used for skin moisturising. Hyaluronic acid coated on the skin surface can quickly form a breathable hydration film wrapped around the skin surface, which softens the skin'の角質層と、さらに皮膚の角質層による活性物質の吸収と利用を高め、このように肌を繊細で滑らかにします[7]。

・アンチエイジング机能:

ヒアルロン酸には、フリーラジカルを除去する働きがあるので、肌の老化を遅らせ、ダメージから肌を守ることができます。

1.2.4他の機能:

Hyaluronic acid has the function of drug-carrying, which can be used as a carrier to embed drugs, not only slow release but also promote drug absorption. Hyaluronic acid also has antibacterial and anti-inflammatory effects [8].

2ヒアルロン酸の応用

2.1健康食品におけるヒアルロン酸の応用

日本では1980年代にヒアルロン酸ベースの口腔衛生製品が普及しました[8]。機能性食品であるヒアルロン酸は、摂取後に直接健康機能を発揮するわけではありませんが、体内のヒアルロン酸合成の前駆体を増加させ、皮膚や他の組織におけるヒアルロン酸の合成を促進します[9]。

2.2化粧品におけるヒアルロン酸の応用

As mentioned earlier, hyaluronic acid has strong moisturising properties and is a naturally occurring substance found in a wide range of skin and other tissues. This property has led to its popularity in the cosmetic industry worldwide [9]. Currently, there are many cosmetic products containing hyaluronic acid in their formulations, such as toners, lotions, serum capsules, masks, body lotions, powders, lipsticks, shampoos, sunscreens, conditioners, mousses, and so on [10].

2.2.1 Moisturising:

保湿が主な機能です化粧品におけるヒアルロン酸。グリセリン、に比べ使われるhumectantsプロピレンなどに対しては、低いヒアルロン酸が最强吸湿性ことで相対湿度(33%未満)、理解されていなくて弱い力吸湿性相対湿度が高く(75%以上)、肌の保護ように適合される四季折々、としての要求はのmoisturising効果の化粧品别々の高温多湿な环境に(例えば、冬高温多湿夏ドライ)。つまり、ヒアルロン酸の保湿特性は周囲の相対湿度に影響されません[10]。

Of course, the moisturising property of hyaluronic acid is also related to its relative molecular weight, the larger the molecular weight, the stronger the moisturising property; the smaller the molecular weight, the weaker the moisturising property [10]. Hyaluronic acid as a moisturising agent is seldom used alone, but is often used in conjunction with other moisturising agents, so as to complement each other'の強みとより良いホワイトニングと保湿効果を実現します。

2.2.2皮膚栄養の補給:

Exogenous supplementation of hyaluronic acid can be used as a supplement to the skin'sの内因性ヒアルロン酸。関連化粧品を定期的に使用することは、皮膚の栄養素の伝達と代謝の老廃物の排出を促進し、皮膚の水分の一定レベルを維持し、皮膚の老化、美容、スキンケアを遅らせる効果を達成することができます。

2.2.3太陽の保護と損傷した皮膚の修復:

Hyaluronic acid has a certain effect on sun protection, but its mechanism of action is different from that of ordinary sunscreen. Sunscreens often include ultraviolet absorbers to achieve the purpose of sun protection; hyaluronic acid can largely reduce the transmittance of ultraviolet rays and repair skin damage caused by the small amount of ultraviolet rays that pass through. When the skin is exposed to sunlight, resulting in redness, burning pain, peeling, etc., cosmetics containing hyaluronic acid can be used to promote the proliferation and differentiation of epidermal cells, and hyaluronic acid can be used to remove the effect of oxygen free radicals to help the injured part of the skin to recover [10].

2.2.4潤滑性及び成膜性:

Hyaluronic acid has certain lubricating and film-forming properties, which can be used in cosmetics to enhance lubrication, increase the feel of skin care, and make the face feel good, and its film can be formed on the surface of the skin, which can improve the cosmetic effect of the skin, and make the skin have a good feeling of smoothness and moistness. When using shampoo and hair care products containing hyaluronic acid, it is equivalent to coating the surface of the hair with a protective film that lubricates and removes static electricity, which has the effect of making the hair easy to take care of and preventing it from falling off.

2.2.5シェーディング:

Hyaluronic acid has a certain viscosity after absorbing water, and the 1% concentration of aqueous solution is in the form of a gel, which can be added to water, creams and other cosmetics to increase the viscosity and stability.

2.3化粧品注射におけるヒアルロン酸の応用

外国であろうと国内の大都市であろうと、注射の化粧品技術は今日人気のある化粧品技術です。フィラーの皮下注射を通じて、皮膚のしわは、このような唇の増加、あごの増加、鼻形成術や他の美容整形手術は、一度充填剤としてコラーゲン溶液を使用したように、迅速に排除することができます。

Although natural collagen, like hyaluronic acid, is the main component of the extracellular matrix of animal connective tissues, the commercial collagen used in the cosmetic market is generally a protein extracted from animal tissues, and its structure and amino acid composition are not exactly the same as that of collagen in human tissues, so it has a certain degree of immunogenicity, and once injected subcutaneously, it will most likely cause immune response, leading to serious consequences and physical harm and economic losses to consumers. This can lead to serious consequences, causing bodily harm and economic loss to the consumer. Therefore, when using natural collagen as a cosmetic filler, it is necessary to conduct a ‘skin test’ [10].

Hyaluronic acid soft-tissue fillers can be injected or used surgically to eliminate crow'の足、鼻唇ひだ、およびある程度の他の顔のしわ。唇の拡大充填剤は、顔の萎縮やにきびや治癒痕などの顔の傷跡によって引き起こされる局所的な崩壊を減らすことができます。架橋ヒアルロン酸フィラーは永続的ではなく、数ヶ月後には組織に分解され吸収されるため、豊胸術には使用できません。

2.4ヒアルロン酸の整形外科アプリケーション

2.4.1関節疾患の治療におけるアプリケーション:

Hyaluronic acid is the main component of cartilage and synovial fluid, and its physiological properties play an irreplaceable role in the function of joints [10]. Abnormalities in the production and metabolism of hyaluronic acid in the joints can lead to the deterioration of osteoarthritis, rheumatoid arthritis, and other infectious and non-infectious joint diseases, as well as to the degradation and destruction of cartilage.

関節疾患の治療において、ヒアルロン酸を注入して滑膜液を補充し、代替することができます。主に外因性ヒアルロン酸を補充して、軟骨の修復を促進し、滑膜液の潤滑能力を回復させ、関節の機能を向上させます[11]。

2.4.2術後癒着の予防における適用:

Hyaluronic acid has been widely used to prevent postoperative tissue adhesions. As early as 1980, hyaluronic acid was first successfully used in the treatment of tendon repair in order to reduce postoperative adhesions. Numerous animal studies and clinical trials have shown that hyaluronic acid is a safe and effective substance for the prevention and reduction of post-surgical tissue adhesions [12].

2.5眼科治療におけるヒアルロン酸

2.5.1動物の眼におけるヒアルロン酸の分布と役割:

As an acidic mucopolysaccharide, hyaluronic acid is distributed in the intercellular matrix of various tissues in animals, and has the important physiological functions of maintaining a stable osmotic pressure in cells and bonding adjacent cells [13]. The content of hyaluronic acid in the vitreous humor of animal eyes is high, and the content of hyaluronic acid in the vitreous humor of adult animals is higher than that of juvenile animals. Of course, the distribution of hyaluronic acid in the vitreous body of the eye is not uniform, with a low level of hyaluronic acid in the middle of the vitreous body of the eye and a high level of hyaluronic acid in the vicinity of the ciliary body.

2.5.2ヒアルロン酸ナトリウムは眼科手術に使用される:

ヒアルロン酸は、主にその粘性、擬似可塑性、弾力性、接着性、コーティング性の性質のために眼科手術に広く応用されています。そのため、粘弾性クッション性、組織内剝離性、粘弾性閉塞性、粘弾性止血性、粘弾性クッション性、弾性固定性などの重要な機能があります[14]。

Currently, hyaluronic acid is used as a viscoelastic agent in many ophthalmic surgeries, such as retina-related surgeries, cataract-related surgeries, and artificial lens-related surgeries.

The ヒアルロン酸のナトリウム塩 plays a very important role in IOL implantation and cataract surgery. For example, hyaluronic acid-Na can be injected into the anterior chamber of the cornea in order to form a protective layer in the cornea'は、内皮細胞損失の速度を減少させるだけでなく、機械的せん断およびiolsの移植による内皮細胞への損傷の影響を減少させるだけでなく、内皮、;さらに、レンズを角膜に埋め込むために、前室にヒアルロン酸を注入することもできます。さらに、前房を深くしてレンズカプセルを開くことで、前房iolを前房内に容易にスライドさせ、円滑なレンズ移植を可能にする[15]。

By injecting hyaluronic acid into the anterior chamber, the normal depth of the anterior chamber can be maintained, the complications of insufficient aqueous secretion and choroidal detachment after glaucoma surgery can be reduced, the occurrence of shallow anterior chamber can be prevented, and the injection of hyaluronic acid-Na in the anterior chamber and subconjunctival valve can reduce the rate of haemorrhage, post-surgical scarring and post-surgical adhesion, and increase the rate of functional follicle formation. Therefore, the use of hyaluronan-Na in ophthalmic surgery can better prevent the formation of postoperative scarring, reduce intraocular pressure and the incidence of shallow anterior chamber and choroidal detachment, and is a safe, reliable, and effective treatment for glaucoma [16].

Hyaluronic acid-Na also plays an important role in corneal surgery, mainly in its protective effects on tissues, such as avoiding damage to intraocular tissues by surgical instruments, reducing astigmatism in the postoperative period, reducing the sudden loss of aqueous humor, avoiding postoperative adhesions, and facilitating postoperative recovery of epithelial tissues. The use of hyaluronic acid-Na in corneal transplantation can effectively protect the corneal tissue and promote the recovery of the transparency of the corneal implant [16].

2.5.3眼の潤滑におけるヒアルロン酸ナトリウムの役割:

Dry eye disease is a common comprehensive ophthalmic disease, which is mainly caused by the dysfunction of certain ocular gland cells, including various types of conjunctivitis. Hyaluronic acid-Na has a prolonged residence time in the eye due to its non-Newtonian fluid properties. Hyaluronic acid-Na also has more hydrophilic groups, which can combine with water molecules to achieve hydrophilicity and lubrication, so it can alleviate the symptoms of dry eyes to a certain extent. This is because when blinking, hyaluronic acid-Na has a certain degree of viscoelasticity like tear mucin, so it can replace the role of tear mucin and alleviate the discomfort of dry eyes [17].

2.5.4眼科製剤におけるヒアルロン酸の役割:

The properties of dilute solution of hyaluronic acid are close to those of tear fluid, which belongs to non-Newtonian fluid, and its viscosity and elasticity are the same as those of animal tear fluid, with good biotolerance. Therefore, hyaluronic acid solution can be used as a pharmaceutical medium to thicken ophthalmic preparations, and its effect is better than the general chemical thickeners.

Currently, hyaluronic acid-Na is also widely used as an ophthalmic agent to treat intraocular inflammation by intraocular injection of highly concentrated hyaluronic acid mixed with anti-inflammatory drugs in a gel. This method is different from systemic medications such as oral medications or intravenous injections, and it has the characteristics of quick effect and less frequent administration, which can reduce the pain of patients [17].

2.5.5眼科におけるヒアルロン酸の他の応用:

上記の応用に加えて、ヒアルロン酸は、眼の外傷、前室出血除去、眼球外筋手術、眼球形成手術など、眼科における多くの臨床応用においても役割を果たしています。

2.5.6弊害:

Increased intraocular pressure is a common complication following ophthalmic surgery due to blockage of ocular outflow pathways, e.g., tissue debris, tissue oedema, and tissue residue [17]. This complication occurs mainly a few hours after injection and peaks when the postoperative intraocular pressure normalises, and the peak intraocular pressure is related to the concentration of hyaluronan-Na. In order to reduce the postoperative increase in intraocular pressure and in patients with glaucoma, it is generally recommended that hyaluronan be aspirated or flushed out of the anterior chamber after surgery.

眼の手術で使用されるヒアルロン酸がに、ティミー・確信場合によって濁らせが生じてしまう24時間以内、ティミーも、数週間続けタンパク質などの不純物のせいが主や残留核酸ヒアルロン酸立案、ダメージ外科に楽器として、残差の組織破片で血液〔17〕措置を取らなかったのは、撤去させる。

2.6ヒアルロン酸の他の用途

2.6.1泌尿器科での応用:

Hyaluronic acid can be injected directly into the bladder as a temporary replacement for the lack of a protective layer of bladder epithelial glycosaminoglycans, thus achieving the purpose of treating interstitial cystitis [18]. Currently, hyaluronic acid is being used for a wider range of indications than just interstitial cystitis, which provides a broader market opportunity for hyaluronic acid products [19].

2.6.2疾患診断への応用:

体内のヒアルロン酸濃度が多くの疾患の発症に有意な増加を示していることを考えると、血清中のヒアルロン酸の測定を通じて、様々な疾患の変化を反映することが可能です。

3ヒアルロン酸の製造方法

ヒアルロン酸は、動物組織からの抽出と微生物発酵という2つの方法で製造されます。その中でも、現在のヒアルロン酸生産の主な方法は微生物発酵です。

3.1動物組織抽出

ヒアルロン酸は、ほとんどすべての動物組織に存在し、広く分布しています。ヒアルロン酸抽出に使用できる動物性素材としては、主に鶏冠やカウのガラス体が挙げられます#というように39の目、および人間のへその緒と。主な操作方法は以下の通りです。

Raw materials → acetone or ethanol to raw materials degreasing, dehydration, air drying → soaked in distilled water, filtration → aqueous sodium chloride and chloroform solution treatment → add trypsin insulation → ion exchange agent treatment, purification → refined hyaluronic acid.

動物組織の抽出法は、新鮮で安全でなければならない原料に対するより高い要件があります。原料动物の組織が高価なものを、しかもするのは難しいのは実の父のことは生育周期のが大きく影響していると四季動物や、での純度ヒアルロン酸动物組織は高くない原材料は、动物の抽出に増産は低い。、

The extraction of hyaluronic acid is complicated by the consumption of large amounts of organic solvents and hydrolytic enzymes, and the number of operating units increases the cost of hyaluronic acid extraction. In addition, due to the low purity of hyaluronic acid extracted from animal tissues, further refinement and purification of the product is more complicated, which limits the application of the product. The extraction method can no longer meet the current market needs, so fermentation has basically replaced the extraction method for the production of hyaluronic acid [20].

3.2微生物発酵

The production of hyaluronic acid by microbial fermentation has been studied since the 1930s. Since hyaluronic acid in the fermentation broth exists in a free state, it is easy to isolate and purify hyaluronic acid. Therefore, the production of hyaluronic acid by microbial fermentation method has more advantages than that by animal tissue extraction method, such as low production cost and unlimited scale of raw materials.

There are two types of streptococci that can produce hyaluronic acid: group A and group C. Group A mainly includes Streptococcus pyogenes, which is generally not used as a production strain because of its strong pathogenicity; group C includes Streptococcus zooepidemicus, Streptococcus equi, and Streptococcus equi, etc., which are all used in the production of hyaluronic acid, and are also used in the production of hyaluronic acid. Group C includes S. zooepidemicus, S. equi, S. equisimilis, etc., all of which are non-pathogenic bacteria, so they can be used as hyaluronic acid production strains [21]. Luo Ruiming et al. [22] isolated Streptococcus zooepidemicus strain NUF-035 from the lung fluid of sheep with pneumonia, and the yield of hyaluronic acid obtained by optimising the medium was 1.88 g/L. Feng Jiansheng et al.

feng jianjianら[23]は、streptococcus equi sh0を出発株として、物理的および化学的変異原法により、遺伝的に安定な非溶血ヒアルロニダーゼ欠損株sh0201を選択し、シェイクフラスコ発酵により相対分子量2.06×106 daのヒアルロン酸を得た。li zigangら[24]は、乳牛の鼻粘膜からstreptococcus faecalis株を単離し、uv変異誘発とニトロソグアニジン変異誘発後のヒアルロン酸の収率は6.94 g/ lに達した。

The quality and yield of hyaluronic acid produced by microbial fermentation are mainly affected by the following aspects: the selection of strains, the optimisation of medium and fermentation conditions, and the downstream technology of biotechnology, i.e., the extraction of hyaluronic acid [25-27]. So far, many scholars at home and abroad have conducted research on the production of hyaluronic acid by microbial fermentation.

Guo Xueping et al. [28] carried out research on the fermentation production process of hyaluronic acid, and carried out laboratory pilot and production workshop pilot studies; Chen Yonghao et al. [29] used γ-rays and ultraviolet rays in combination with irradiation for mutation breeding, and obtained non-haemolytic strains, so that the yield of hyaluronic acid and relative molecular mass has been further improved; Yang Li et al. Yang Li et al. [30] explored the factors affecting the molecular weight of hyaluronic acid, and obtained the relationship between the dissolved oxygen level and stirring speed and the molecular weight of hyaluronic acid; Fu Li et al. [31] screened a hyaluronic acid-producing bacterium from the natural world; Ye Hua et al. [32] studied the process of adding hyaluronic acid to the fermentation medium; Shi Peng [33] researched on the process of hyaluronic acid production and extraction by the fermentation method; Hao Ning et al. Hao Ning et al. [34] carried out genetic modification of hyaluronic acid producing bacteria, and the yield of hyaluronic acid produced by recombinant bacteria was greatly improved.

Holmstrm [35] and Johns [36] optimized the fermentation nutrient conditions of hyaluronic acid by shaking flasks and then fermenting in small fermentation tanks; Kim et al [37] selected Streptococcus zooepidemicus and optimized the cultivation conditions; Armstrong [38] and Chong [39] studied the fermentation conditions of hyaluronic acid. 38] and Chong [39] obtained the relationship between the culture conditions of hyaluronic acid-producing bacteria on the yield and molecular weight of hyaluronic acid.

The main process of hyaluronic acid fermentation production is as follows: slant seed → shake bottle seed → inoculation → fermentation culture → replenishment → tank placement → fermentation broth (crude extraction with ethanol) → crude extraction (add filter aid, activated carbon, adjust pH value) → filtration (remove impurities) → filtrate (ethanol precipitation) → precipitate (dehydration and drying) → product hyaluronic acid [40-41].

4展望

The market demand and sales of hyaluronic acid are increasing every year. The research and development of hyaluronic acid mainly focuses on the molecular modification of hyaluronic acid and the application of its derivatives in various industries. The selection of strains, optimisation of fermentation conditions, improvement of the extraction process and analytical modifications can expand the range of applications of hyaluronic acid and increase its economic value.

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