히알루론산 분말의 용도는 무엇인가요?

루 론 산, 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. 이molecular 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.

히알루론산의 물리적, 화학적 성질과 생리적 기능 1

물리적, 화학적 성질 1.1

히알루론산은 물에 용해되며 용액은 일정한 음전하를 띤 산성이다.루 론 산은 높은 분자 다당류의 분자의 disaccharide 단위의 결합에 의해 형성 된 β 산과 β-D-glucuronic-D-N-acetylglucosaminoglucose다.

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. 이specific 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 생리적 기능

1.2.1 물 보유 기능:

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 피부 보호:

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's 각질층 그리고 피부의 각질층에 의한 활성물질의 흡수와 활용을 더욱 향상시켜 [7] 피부를 연약하고 매끄럽게 해준다.

1.2.3 안티 에이징 기능:

히알루론산은 활성산소를 제거하는 기능이 있기 때문에 피부 노화를 늦추고 손상으로부터 피부를 보호할 수 있다.

1.2.4기타 기능:

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].

히알루론산 적용 2

2.1 히알루론산의 건강식품 활용

1980년대 일본에서 히알루론산을 원료로 한 구강 건강 제품이 인기를 끌었다 [8].기능성 식품으로서 히알루론산은 섭취 후 직접적으로 건강 기능을 발휘하지는 않지만, 체내에서 히알루론산의 합성을 위한 전구체를 증가시키고 피부와 기타 조직에서 히알루론산의 합성을 촉진한다 [9].

화장품의 히알루론산 활용 2.2

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 보습:

보습은의 주요 기능이다화장품에 들어있는 히알루론산다.히알루론산은 글리세롤, 프로필렌 글리콜 등 일반적으로 사용되는 휴메트렉트제와 비교하여 낮은 상대습도 (33% 이하)에서 가장 강한 흡습성을 보이고 높은 상대습도 (75% 이상)에서 가장 약한 흡습성을 나타내 계절별 피부보호에 적합하며, 습한 환경 (예:건조한 겨울과 습한 여름)에 따라 화장품의 보습 효과에 대한 요구량이 다르기 때문이다.즉, 히알루론산의 보습 특성은 주변 환경의 상대 습도에 영향을 받지 않는다 [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's 강점 및 더 나은 미백 및 보습 효과를 얻습니다.

2.2.2 피부 영양의 보충:

Exogenous supplementation of hyaluronic acid can be used as a supplement to the skin's 내인성 히알루론산.관련 화장품을 규칙적으로 사용하면 피부 노화를 지연시키는 효과, 미용 및 피부 관리 효과를 얻기 위해 피부 영양소의 이동과 대사 노폐물 배출, 피부 내 일정 수준의 수분 함량을 유지하는 데 도움이 된다.

2.2.3자외선 차단 및 손상된 피부 회복:

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 윤활 및 필름 형성 특성:

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.

2.2.5이 두 꺼 워 졌다:

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.

화장품 주사의 히알루론산 활용 2.3

외국이든 국내 대도시든 주사 성형 기술은 오늘날 인기 있는 성형 기술이다.일단 콜라겐 용액을 필러로 사용한 입술확대술, 턱확대술, 코성형술 등 성형수술시 필러의 피하주사를 통해 피부 주름을 빠르게 없앨 수 있다.

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's 발, 팔자주름, 기타 얼굴 주름이 어느 정도.입술 확대 필러는 얼굴 위축과 여드름 및 치유 흉터와 같은 일부 얼굴 흉터로 인한 국소 붕괴를 줄일 수 있습니다.교차 연결된 히알루론산 필러는 영구적이지 않고 몇 개월 후 분해되어 조직에 흡수되므로 가슴 확대 수술에 사용할 수 없습니다.

히알루론산의 정형외과 응용 2.4

2.4.1 관절질환 치료에 적용:

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.

관절 질환 치료에서는 히알루론산을 주입하여 활액을 보충하고 대체하는데, 주로 외인성 히알루론산의 보충을 통해 연골의 회복을 촉진하고 활액의 윤활능력을 회복시켜 관절의 기능을 향상시킨다 [11].

2.4.2 수술 후 유착 예방에 적용:

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].

안과 치료시 히알루론산 2.5

2.5.1 동물 눈에서의 히알루론산의 분포와 역할:

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 히알루론산나트륨은 안과 수술에 사용됩니다:

히알루론산은 주로 점도, 가성성, 탄성, 접착력, 코팅성 등의 성질로 인해 점탄성 완충, 조직 내 박리, 점성 차단, 점성 지혈, 점탄성 쿠션, 탄성 고정 등과 같은 중요한 기능을 가지게 되어 안과수술에 다양하게 응용된다 [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 히알루론산의 소금 나트륨 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'는 내피세포 손실 속도를 감소시킬 뿐만 아니라 기계적 전단 및 IOLs의 착상으로 인해 내피세포에 미치는 해로운 영향을 감소시키는 s 내피;뿐만 아니라 각막에 수정체를 이식하기 위해서는 히알루론산을 전방으로 주입할 수 있다.또한, 전방을 깊게하고 렌즈 캡슐을 열어 전방 IOL이 손쉽게 전방으로 미끄러져 들어가 매끄러운 렌즈 착상을 할 수 있도록 하는 것도 사용할 수 있다 [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 눈 윤활에서 히알루론산 나트륨의 역할:

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 안과 조제에서 히알루론산의 역할:

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 안과에서 히알루론산의 기타 응용:

위의 응용 외에도 히알루론산은 안구 외상, 전방 출혈 제거, 외안근 수술 및 안구 성형 수술과 같은 안과의 다른 많은 임상 응용 분야에서도 역할을 합니다.

2.5.6 부작위:

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.

히알루론산을 안구수술에 사용할 경우 간혹 24시간 이내에 염증반응과 수용액 혼탁이 일어날 수 있으며, 일부 염증반응은 수주 동안 지속될 수 있는데, 이는 주로 히알루론산 제형의 단백질이나 핵산 잔류 등의 불순물과 수술 기구의 손상, 잔류 조직 잔해, 혈액을 제때 제거하지 못한 것 [17] 등이 원인이 된다.

히알루론산의 기타 용도 2.6

2.6.1 비뇨기과의 응용:

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 질병 진단에의 응용:

체내의 히알루론산 수치가 많은 질병의 발병시 현저한 증가를 보인다는 점을 감안할 때, 혈청 내 히알루론산 측정을 통해 다양한 질병의 변화를 반영할 수 있다.

히알루론산의 생산 방법 3

히알루론산은 동물 조직 추출과 미생물 발효의 두 가지 방법으로 생성할 수 있습니다.그 중 미생물 발효는 현재 히알루론산 생산의 주요 방법이다.

3.1 동물 조직 추출

히알루론산은 거의 모든 동물의 조직에 존재하며 널리 분포되어 있다.히알루론산 추출에 사용할 수 있는 동물성 소재로는 주로 치킨크라운과 카우&의 유리체 등이 있다#39;의 눈, 그리고 인간의 탯줄 등등.주요 작동 절차는 다음과 같습니다:

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.

동물 조직 추출 방법은 신선하고 안전해야 하는 원료에 대한 요구사항이 더 높습니다.동물 조직의 원료는 비싸며, 일부를 얻기 어려워 동물의 성장 주기와 계절에 큰 영향을 받기 때문에 동물 조직 원료 중 히알루론산의 순도가 높지 않고, 추출 수율이 낮다.

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 미생물 발효

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.

풍장자 등 23은 Streptococcus equi SH0을 출발균주로 사용하고 물리적, 화학적 돌연변이 발생에 의해 유전적으로 안정하고 용혈성이 없고 히알루로니다제가 부족한 균주 SH0201을 선발하여 쉐이크 플라스크 발효에 의해 상대분자량이 2.06×106 Da인 히알루론산을 얻었다.이지강 등 [24]은 젖소의 코 점막에서 Streptococcus faecalis 균주를 분리하였으며, 히알루론산의 생산량은 자외선 돌연변이 발생 및 니트로소구아니딘 돌연변이 발생 후 6.94 g/L에 도달할 수 있었다.

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 전망

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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