KR20230067034A - Method for producing lactoferrin derivative having functions such as antioxidant, whitening, anti-inflammatory and skin protection, and skin treatment ointment and cosmetic composition comprising the same - Google Patents
Method for producing lactoferrin derivative having functions such as antioxidant, whitening, anti-inflammatory and skin protection, and skin treatment ointment and cosmetic composition comprising the same Download PDFInfo
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- KR20230067034A KR20230067034A KR1020210152679A KR20210152679A KR20230067034A KR 20230067034 A KR20230067034 A KR 20230067034A KR 1020210152679 A KR1020210152679 A KR 1020210152679A KR 20210152679 A KR20210152679 A KR 20210152679A KR 20230067034 A KR20230067034 A KR 20230067034A
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- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical class C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims abstract description 39
- 239000002537 cosmetic Substances 0.000 title claims description 20
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- 230000002087 whitening effect Effects 0.000 title abstract description 7
- 230000006870 function Effects 0.000 title abstract description 5
- 239000003963 antioxidant agent Substances 0.000 title abstract description 4
- 230000003110 anti-inflammatory effect Effects 0.000 title abstract description 3
- 230000003078 antioxidant effect Effects 0.000 title abstract description 3
- 239000002674 ointment Substances 0.000 title description 5
- 229940078795 lactoferrin Drugs 0.000 claims description 50
- 108010063045 Lactoferrin Proteins 0.000 claims description 39
- 235000021242 lactoferrin Nutrition 0.000 claims description 37
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 27
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical class CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 18
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 12
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- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 3
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/79—Transferrins, e.g. lactoferrins, ovotransferrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
Abstract
본 발명은 락토페린 유도체를 포함하는 조성물 및 이의 제조방법에 관한 것으로, 본 발명에 의해 항산화, 미백, 항염증, 피부보호 등의 기능을 가지고, 화학적으로 안정하며, 생리활성이 뛰어난 락토페린 유도체를 포함한 조성물을 제공할 수 있다. The present invention relates to a composition containing a lactoferrin derivative and a method for preparing the same. The composition containing the lactoferrin derivative has antioxidant, whitening, anti-inflammatory, and skin protection functions, is chemically stable, and has excellent physiological activity. can provide.
Description
본 발명은 락토페린 유도체를 포함하는 조성물 및 이의 제조방법에 관한 것으로, 본 발명에 의해 항산화, 미백, 항염증, 피부보호 등의 기능을 가지고, 화학적으로 안정하며, 생리활성이 뛰어난 락토페린 유도체를 포함한 조성물을 제공할 수 있다.The present invention relates to a composition containing a lactoferrin derivative and a method for preparing the same. The composition containing the lactoferrin derivative has antioxidant, whitening, anti-inflammatory, and skin protection functions, is chemically stable, and has excellent physiological activity. can provide.
피부는 외부 환경과 항상 접하고 있는 기관으로서, 수분 손실을 막는 보호 장벽으로서의 역할을 수행하는 것이 일반적이다. 이러한 피부 수분의 건조를 막기 위하여, 피부는 표피층에서 분화 과정을 통하여 수분을 함유하면서 얇은 각질층으로 발달하게 된다. The skin is an organ that is always in contact with the external environment, and generally serves as a protective barrier preventing water loss. In order to prevent such drying of skin moisture, the skin develops into a thin stratum corneum while containing moisture through a differentiation process in the epidermal layer.
각질층은 외부 환경과 직접 접촉하는 피부 최외각층으로서 기계적, 화학적으로 유해한 성분의 침입을 방지하고, 생체 내보다 건조한 외부환경으로 부터 내부 수분이 손실되는 것을 막아주는 동시에, 각질층 자신도 적당한 수분을 보유하여, 유연성을 유지하고 있으나, 강한 자외선, 과도한 세안제 사용, 스트레스 및 자연적인 노화 현상이 발생한다.The stratum corneum is the outermost layer of the skin that is in direct contact with the external environment. It prevents mechanically and chemically harmful ingredients from entering, and prevents loss of internal moisture from the external environment drier than the living body. , but maintains flexibility, strong ultraviolet rays, excessive use of face wash, stress, and natural aging occur.
이러한 피부 손상을 예방, 개선 또는 치료하기 위하여 다양한 생리활성의 기능을 가지는 락토페린(Lactoferrin; LF)이 화장품 또는 외용제를 위한 용도로 연구되어 왔으나, 분자량이 80kDa으로 거대하여 피부침투가 용이하지 않은 문제점이 있다. In order to prevent, improve, or treat such skin damage, Lactoferrin (LF), which has various physiologically active functions, has been studied for use in cosmetics or external preparations, but has a problem of not easy skin penetration due to its huge molecular weight of 80 kDa. there is.
따라서, 본 발명은 상기한 실정을 고려하여 종래 기술들에서 야기되는 여러 가지 결점 및 문제점들을 해결하고자 하는 것으로서, 락토페린(Lactoferrin)에 피부침투가 용이한 히아루론산(Hyaluronic acid)을 결합한 Hyaluronoyl lactoferrin을 합성하여, 히아루론산과 락토페린의 기능성을 제고시키는 것을 목적으로 한다. Therefore, the present invention is to solve various drawbacks and problems caused by the prior art in consideration of the above situation, by synthesizing Hyaluronoyl lactoferrin, which is a combination of hyaluronic acid that is easily penetrated into the skin to lactoferrin. , It aims to improve the functionality of hyaluronic acid and lactoferrin.
또한, 본 발명이 해결하고자 하는 과제들은 이상에서 언급된 과제로 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 통상의 기술자에게 명확하게 이해될 수 있을 것이다. In addition, the problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.
상기와 같은 목적을 달성하기 위하여 본 발명의 일 실시예에 따르면, 락토페린 유도체를 유효성분으로 포함하는, 염증성 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.According to one embodiment of the present invention in order to achieve the above object, it is to provide a pharmaceutical composition for preventing or treating inflammatory diseases, containing a lactoferrin derivative as an active ingredient.
또한 본 발명에서, 상기 락토페린 유도체는 화학식 1 및 2에서 선택된 어느 하나 이상의 단위를 포함하는 축합중합체인 것이다.Also, in the present invention, the lactoferrin derivative is a condensation polymer containing at least one unit selected from Chemical Formulas 1 and 2.
[화학식 1][Formula 1]
[화학식 2][Formula 2]
상기 화학식 1에서 M+은 금속 양이온이고, 상기 화학식 1 및 2에서 LF는 락토페린을 포함하는 것이다.In Formula 1, M + is a metal cation, and LF in Formulas 1 and 2 includes lactoferrin.
또한 본 발명에서, 상기 축합중합체는 화학식 3으로 표시될 수 있는 단위를 더 포함하는 것이다.In the present invention, the condensation polymer further includes a unit represented by Chemical Formula 3.
[화학식 3][Formula 3]
본 발명의 다른 실시예에 따르면, 락토페린 유도체를 유효성분으로 포함하는, 피부 개선용 화장료 조성물에 관한 것일 수 있다.According to another embodiment of the present invention, it may relate to a cosmetic composition for skin improvement containing a lactoferrin derivative as an active ingredient.
본 발명의 또 다른 실시예에 따르면, 히아루론산에 시료를 첨가하는 단계; 락토페린을 첨가하는 단계; 및 정제 용매를 첨가하여 정제하는 단계;를 포함하는, 락토페린 유도체를 제조하는 방법에 관한 것일 수 있다.According to another embodiment of the present invention, adding a sample to hyaluronic acid; adding lactoferrin; It may relate to a method for preparing a lactoferrin derivative, including; and purifying by adding a purification solvent.
본 발명의 락토페린 유도체는 락토페린(Lactoferrin)에 피부침투가 용이한 히아루론산(Hyaluronic acid)을 결합한 히아루로닐 락토페린(Hyaluronoyl lactoferrin)으로, 히아루론산과 락토페린의 높은 기능성을 제고시킬 수 있다. The lactoferrin derivative of the present invention is hyaluronoyl lactoferrin obtained by combining lactoferrin with hyaluronic acid, which is easily penetrated into the skin, and can improve the high functionality of hyaluronic acid and lactoferrin.
본 발명의 효과들은 이상에서 언급된 효과로 제한되지 않으며, 언급되지 않은 또 다른 효과들은 아래의 기재로부터 통상의 기술자에게 명확하게 이해될 수 있을 것이다.The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.
도 1은 본 발명의 일 실시예에 따른 oxidized Hyaluronic Acid와 Lactoferrin이 couping 시약을 사용하여 아미드 결합한 형태를 나타낸 것이다.
도 2는 본 발명의 일 실시예에 따른 oxidized Hyaluronic Acid와 Lactoferrin이 Imine을 형성한 후 환원된 형태를 나타낸 것이다.
도 3은 본 발명의 일 실시예에 따라, N-Hyaluronyl-Lactoferrin(NHL) 및 oxHA-lactoferrin(oxi-HLF)의 처리 시 세포에 미치는 독성을 알아보기 위하여 피부각질형성세포주 HaCaT의 증식률을 MTT assay를 이용하여 측정한 결과이다.
도 4는 본 발명의 일 실시예에 따라, N-Hyaluronyl-Lactoferrin(NHL) 및 oxHA-lactoferrin(oxi-HLF)의 처리 농도에 따른 UVB에 의한 세포 사멸 억제 효과를 알아보기 위하여 피부각질형성세포주 HaCaT의 증식률을 MTT assay를 이용하여 측정한 결과이다.
도 5는 본 발명의 일 실시예에 따라, N-Hyaluronyl-Lactoferrin(NHL) 및 oxHA-lactoferrin (oxi-HLF)의 처리 시 농도에 따른 활성산소(Reactive Oxygen Species) 감소 효과를 확인하기 위하여 UVB를 조사한 후 흡광도를 측정해 비교한 결과이다.
도 6은 본 발명의 일 실시예에 따라, N-Hyaluronyl-Lactoferrin(NHL) 및 oxHA-lactoferrin(oxi-HL)의 처리 시 세포의 염증 반응에 미치는 영향을 알아보기 위하여 콜라겐분해효소 MPP-1의 유전자 발현을 실시간 유전자증폭기(PCR)를 이용하여 확인한 결과이다.
도 7은 본 발명의 일 실시예에 따라, N-Hyaluronyl-Lactoferrin(NHL) 및 oxHA-lactoferrin(oxi-HL)의 처리 시 세포의 염증 반응에 미치는 영향을 알아보기 위하여 종양괴사인자 TNF-α의 유전자 발현을 실시간 유전자증폭기(PCR)를 이용하여 확인한 결과이다.
도 8은 본 발명의 일 실시예에 따라, N-Hyaluronyl-Lactoferrin(NHL) 및 oxHA-lactoferrin(oxi-HLF)의 처리 시 세포의 미백에 미치는 영향을 알아보기 위하여 B16F10 흑색종 세포의 멜라닌 합성 감소 효과를 측정한 결과이다.1 shows an amide bond between oxidized Hyaluronic Acid and Lactoferrin using a coupling reagent according to an embodiment of the present invention.
2 shows a reduced form after oxidized Hyaluronic Acid and Lactoferrin form Imine according to an embodiment of the present invention.
3 is an MTT assay of the proliferation rate of the skin keratinocyte cell line HaCaT to determine the toxicity to cells upon treatment with N-Hyaluronyl-Lactoferrin (NHL) and oxHA-lactoferrin (oxi-HLF) according to an embodiment of the present invention. This is the result measured using
4 is a skin keratinocyte cell line HaCaT in order to examine the effect of inhibiting cell death by UVB according to the treatment concentrations of N-Hyaluronyl-Lactoferrin (NHL) and oxHA-lactoferrin (oxi-HLF) according to an embodiment of the present invention. This is the result of measuring the proliferation rate using the MTT assay.
5 is UVB to confirm the effect of reducing reactive oxygen species according to the concentration upon treatment of N-Hyaluronyl-Lactoferrin (NHL) and oxHA-lactoferrin (oxi-HLF) according to an embodiment of the present invention. This is the result of measuring and comparing absorbance after irradiation.
Figure 6 shows the effect of collagenase MPP-1 on the inflammatory response of cells upon treatment with N-Hyaluronyl-Lactoferrin (NHL) and oxHA-lactoferrin (oxi-HL) according to an embodiment of the present invention. This is the result of confirming gene expression using real-time gene amplification (PCR).
Figure 7 shows the effect of tumor necrosis factor TNF-α on the inflammatory response of cells upon treatment with N-Hyaluronyl-Lactoferrin (NHL) and oxHA-lactoferrin (oxi-HL) according to an embodiment of the present invention. This is the result of confirming gene expression using real-time gene amplification (PCR).
8 is a decrease in melanin synthesis in B16F10 melanoma cells in order to examine the effect on cell whitening when N-Hyaluronyl-Lactoferrin (NHL) and oxHA-lactoferrin (oxi-HLF) are treated according to an embodiment of the present invention. This is the result of measuring the effect.
이하, 상기와 같은 목적을 달성하기 위하여 본 발명에 대하여 상세히 설명하기로 한다. 이에 앞서, 본 명세서 및 특허청구범위에 사용된 용어 또는 단어는 통상적이거나 사전적인 의미로 한정해서 해석되어서는 아니되며, 발명자는 그 자신의 발명을 가장 최선의 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다. 따라서, 본 명세서에 기재된 실시예에 기재된 구성은 본 발명의 가장 바람직한 일 실시예에 불과할 뿐이고 본 발명의 기술적 사상을 모두 대변하는 것은 아니므로, 본 출원시점에 있어서 이들을 대체할 수 있는 다양한 균등물과 변형예들이 있을 수 있음을 이해하여야 한다.Hereinafter, the present invention will be described in detail in order to achieve the above object. Prior to this, terms or words used in this specification and claims should not be construed as being limited to ordinary or dictionary meanings, and the inventor appropriately uses the concept of terms in order to describe his/her invention in the best way. It should be interpreted as a meaning and concept consistent with the technical spirit of the present invention based on the principle that it can be defined in the following way. Therefore, the configuration described in the embodiments described in this specification is only one of the most preferred embodiments of the present invention and does not represent all of the technical ideas of the present invention, so various equivalents and equivalents that can replace them at the time of this application It should be understood that variations may exist.
한편, 본 명세서에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 명세서에서 개시된 다양한 요소들의 모든 조합이 본 출원의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.
Meanwhile, each description and embodiment disclosed in this specification may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed herein fall within the scope of this application. In addition, it cannot be seen that the scope of the present invention is limited by the specific descriptions described below.
본 발명에서, “락토페린(Lactoferrin; LF)”은 락토트랜스페린(lactotransferrin; LTF)이라고도 하며, 트랜스페린 패밀리의 다기능성 단백질 중 하나이며, 우유, 타액, 눈물 및 코 분비와 같은 다양한 분비액에서 광범위하게 나타나는 약 80 kDa의 분자 질량을 갖는 구형 당단백질이다.In the present invention, “Lactoferrin (LF)”, also referred to as lactotransferrin (LTF), is one of the multifunctional proteins of the transferrin family, and is a drug that is widely present in various secretions such as milk, saliva, tears and nasal secretions. It is a globular glycoprotein with a molecular mass of 80 kDa.
본 발명에서, 상기 락토페린은 인간, 소, 말, 염소 또는 양에서 유래하고 서열번호 1 내지 6에서 선택된 어느 하나 이상의 아미노산 서열을 포함하는 것이거나, 합성된 것일 수 있으나, 그 유래는 특별히 한정되지 않는다.In the present invention, the lactoferrin is derived from humans, cows, horses, goats or sheep and includes any one or more amino acid sequences selected from SEQ ID NOs: 1 to 6, or may be synthesized, but its origin is not particularly limited. .
본 발명에서, 락토페린 유도체는 피부침투가 용이한 히아루론산과 결합된 것일 수 있고, 상기 결합으로 상기 락토페린 및 상기 히아루론산의 기능성이 시너지를 발휘할 수 있다.In the present invention, the lactoferrin derivative may be combined with hyaluronic acid, which is easily penetrated into the skin, and the functionalities of the lactoferrin and the hyaluronic acid can exhibit synergy through the combination.
본 발명에서, 상기 “히아루론산(Hyaluronic acid)”은 동물의 조직 속에 들어 있는 산성 다당류의 하나인 것일 수 있다.In the present invention, the "Hyaluronic acid" may be one of acidic polysaccharides contained in animal tissues.
본 발명에서, “축합(condensation)” 내지 “축합 반응”은 유기화합물의 2분자 또는 그 이상의 분자가 반응하여 간단한 분자가 제거되면서 새로운 화합물을 만드는 반응으로, 본 발명에서는 에스터화(esterification)된 것, 펩타이드 결합(peptide bond)이 형성된 것 또는 이민(Imine)이 생성되는 것일 수 있고, 본 발명의 축합중합체는 에스터화된 상기 히아루론산 또는 상기 히아루론산과 공유 결합된 상기 락토페린 유도체를 의미하는 것일 수 있다.
In the present invention, “condensation” or “condensation reaction” is a reaction in which two or more molecules of an organic compound react to form a new compound while simple molecules are removed. In the present invention, esterification , A peptide bond may be formed or an imine may be formed, and the condensation polymer of the present invention may mean the esterified hyaluronic acid or the lactoferrin derivative covalently bonded to the hyaluronic acid.
본 발명의 일 구현 예에 따르면, 락토페린 유도체를 유효성분으로 포함하는 조성물을 제공하는 것이다.According to one embodiment of the present invention, a composition containing a lactoferrin derivative as an active ingredient is provided.
본 발명에서, 상기 락토페린 유도체는 화학식 1 및 2에서 선택된 어느 하나 이상의 단위를 포함하는 축합중합체인 것일 수 있다.In the present invention, the lactoferrin derivative may be a condensation polymer containing at least one unit selected from Chemical Formulas 1 and 2.
[화학식 1][Formula 1]
[화학식 2][Formula 2]
상기 화학식 1에서 M+는 금속 양이온이고, 상기 화학식 1 및 2에서 LF는 락토페린을 포함하는 것이다. 상기 M+의 예시로는 Na+, K+, 0.5Mg2+, 0.5Ca2+ 등이 포함될 수 있으나, 이에 제한되지는 않는다.In Formula 1, M + is a metal cation, and LF in Formulas 1 and 2 includes lactoferrin. Examples of M + may include Na + , K + , 0.5Mg 2+ , 0.5Ca 2+ , and the like, but are not limited thereto.
본 발명에서, 상기 축합중합체는 화학식 3으로 표시될 수 있는 단위를 더 포함하는 것일 수 있다.In the present invention, the condensation polymer may further include a unit represented by Chemical Formula 3.
[화학식 3][Formula 3]
본 발명의 화학식 1 내지 3에서, 상기 O1/2은 상기 축합중합체를 이루는 단위 및 인접 단위가 산소 원자 1개와 각각 공유결합 하고 있는 구조를 나타내는 것이다.In Chemical Formulas 1 to 3 of the present invention, O 1/2 represents a structure in which a unit constituting the condensation polymer and an adjacent unit are covalently bonded to one oxygen atom, respectively.
본 발명의 일 예시에서, 상기 축합중합체는 하기 화학식 4와 같이 나타낼 수 있는 것일 수 있다.In one example of the present invention, the condensation polymer may be represented by Formula 4 below.
[화학식 4][Formula 4]
상기 화학식 4에서 M+은 금속 양이온이고, LF는 락토페린을 포함하는 것이다.
In Formula 4, M+ is a metal cation, and LF includes lactoferrin.
본 발명의 다른 구현 예에 따르면, 히아루론산에 시료를 첨가하는 단계; 락토페린을 첨가하는 단계; 및 정제 용매를 첨가하여 정제하는 단계;를 포함하는, 락토페린 유도체를 제조하는 방법에 관한 것일 수 있다.According to another embodiment of the present invention, adding a sample to hyaluronic acid; adding lactoferrin; It may relate to a method for preparing a lactoferrin derivative, including; and purifying by adding a purification solvent.
본 발명에서, 상기 시료는 산화제 또는 커플링제인 것일 수 있다. 상기 산화제는 상기 히아루론산을 산화시켜 상기 락토페린과 이민(Imine)이 형성되도록 할 수 있고, 상기 커플링제는 상기 히아루론산과 커플링이 되어 상기 락토페린과 축합 반응이 일어나도록 할 수 있다.In the present invention, the sample may be an oxidizing agent or a coupling agent. The oxidizing agent can oxidize the hyaluronic acid to form the lactoferrin and imine, and the coupling agent can couple with the hyaluronic acid to cause a condensation reaction with the lactoferrin.
본 발명에서, 상기 정제하는 단계는 특별히 한정되는 것은 아니며 본 발명이 속하는 기술 분야에서 통상적으로 사용되는 다양한 추출 방법을 이용할 수 있다. 예를 들면, 정제수, 메탄올, 에탄올, 글리세린, 에틸아세테이트, 부틸렌글리콜, 프로필렌글리콜, 디클로로메탄, 헥산의 용매를 각각 단독으로 또는 이들을 2종 이상 혼합한 용매를 정제 용매로 이용하여 정제할 수 있고, 다양한 크로마토그래피에 의한 분리 등 추가로 실시된 다양한 정제 방법도 포함할 수 있다.
In the present invention, the purification step is not particularly limited, and various extraction methods commonly used in the art to which the present invention pertains may be used. For example, purified water, methanol, ethanol, glycerin, ethyl acetate, butylene glycol, propylene glycol, dichloromethane, and hexane solvents each alone or a mixture of two or more of these solvents can be used as a purification solvent for purification. , various additional purification methods such as separation by various chromatographies may also be included.
본 발명의 또 다른 구현 예에 따르면, 본 발명의 조성물은 약학적 조성물인 것일 수 있다. 상기 약학적 조성물은 염증성 질환의 예방 또는 치료용 약학적 조성물일 수 있고, 바람직하게는 피부에 존재하는 염증성 질환의 예방 또는 치료용 약학적 조성물에 관한 것일 수 있다.According to another embodiment of the present invention, the composition of the present invention may be a pharmaceutical composition. The pharmaceutical composition may be a pharmaceutical composition for preventing or treating inflammatory diseases, and preferably may relate to a pharmaceutical composition for preventing or treating inflammatory diseases present in the skin.
본 발명에서, "예방"은 본 발명의 약학적 조성물을 이용하여 본 발명에 기재된 질환들의 증상을 차단하거나, 그 증상을 억제 또는 지연시키는 모든 행위라면 제한없이 포함할 수 있다. In the present invention, "prevention" may include without limitation any act of blocking, suppressing or delaying the symptoms of the diseases described in the present invention using the pharmaceutical composition of the present invention.
본 발명에서, "치료"는 본 발명의 약학적 조성물을 이용하여 상기 열거된 질환들의 증상이 호전 또는 이롭게 변경되는 모든 행위라면 제한없이 포함할 수 있다. In the present invention, "treatment" may include without limitation any action that improves or beneficially changes the symptoms of the diseases listed above using the pharmaceutical composition of the present invention.
본 발명에서, "약학적 조성물"은 캡슐, 정제, 과립, 주사제, 연고제, 분말 또는 음료 형태임을 특징으로 할 수 있으며, 상기 약학적 조성물은 인간을 대상으로 하는 것을 특징으로 할 수 있다. 상기 약학적 조성물은 이들로 한정되는 것은 아니지만, 각각 통상의 방법에 따라 산제, 과립제, 캡슐, 정제, 수성 현탁액 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. In the present invention, the "pharmaceutical composition" may be in the form of capsules, tablets, granules, injections, ointments, powders or beverages, and the pharmaceutical composition may be intended for humans. The pharmaceutical compositions are not limited to these, but may be formulated and used in the form of oral formulations such as powders, granules, capsules, tablets, aqueous suspensions, external preparations, suppositories and sterile injection solutions, respectively, according to conventional methods. .
본 발명의 약학적 조성물은 약제적으로 허용 가능한 담체를 포함할 수 있다. 약제학적으로 허용되는 담체는 경구 투여 시에는 결합제, 활탁제, 붕해제, 부형제, 가용화제, 분산제, 안정화제, 현탁화제, 색소, 향료 등을 사용할 수 있으며, 주사제의 경우에는 완충제, 보존제, 무통화제, 가용화제, 등장제, 안정화제 등을 혼합하여 사용할 수 있으며, 국소투여용의 경우에는 기제, 부형제, 윤활제, 보존제 등을 사용할 수 있다. 본 발명의 약제학적 조성물의 제형은 상술한 바와 같은 약제학적으로 허용되는 담체와 혼합하여 다양하게 제조될 수 있다. 예를 들어 용액, 현탁액, 정제, 캡슐, 서방형 제제 등으로 제형할 수 있다.The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers may include binders, lubricants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, pigments, flavors, etc. for oral administration, and buffers, preservatives, and painless agents for injections. A topical, solubilizing agent, isotonic agent, stabilizer, etc. may be mixed and used, and in the case of topical administration, a base, excipient, lubricant, preservative, etc. may be used. The dosage form of the pharmaceutical composition of the present invention may be variously prepared by mixing with a pharmaceutically acceptable carrier as described above. For example, it may be formulated as a solution, suspension, tablet, capsule, sustained release formulation, and the like.
한편, 제제화에 적합한 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말디톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유 등이 사용될 수 있다. 또한, 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다.On the other hand, examples of carriers, excipients and diluents suitable for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil and the like can be used. In addition, fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, and the like may be further included.
본 발명의 약학적 조성물은 사용된 특정 화합물의 활성, 연령, 체중, 일반적인 건강, 성별, 정식, 투여시간, 투여경로, 배출율, 약물 배합 및 예방 또는 치료될 특정 질환의 중증을 포함한 여러 요인에 따라 다양하게 변할 수 있고, 상기 약학적 조성물의 투여량은 환자의 상태, 체중, 질병의 정도, 약무형태, 투여경로 및 기간에 따라 다르지만 당업자에 의해 적절하게 선택될 수 있고, 1일 0.0001mg/kg 내지 50mg/kg 또는 0.001mg/kg 내지 50mg/kg으로 투여할 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명에 따른 약학적 조성물은 환제, 당의정, 캡슐, 액제, 겔, 시럽, 슬러리, 현탁제로 제형될 수 있다.The pharmaceutical composition of the present invention depends on various factors including the activity of the specific compound used, age, body weight, general health, sex, diet, administration time, route of administration, excretion rate, drug combination and severity of the specific disease to be prevented or treated. It can vary widely, and the dosage of the pharmaceutical composition varies depending on the patient's condition, body weight, degree of disease, drug form, administration route and period, but can be appropriately selected by those skilled in the art, and is 0.0001 mg/kg per day. to 50 mg/kg or 0.001 mg/kg to 50 mg/kg. Administration may be administered once a day, or may be administered in several divided doses. The dosage is not intended to limit the scope of the present invention in any way. The pharmaceutical composition according to the present invention may be formulated as a pill, dragee, capsule, liquid, gel, syrup, slurry, or suspension.
본 발명에서, 상기 외용제는 화장품학 또는 피부과학적으로 허용가능한 매질 또는 기제를 함유하여 제형화 될 수 있다. 이는 국소적용에 적합한 모든 제형으로서, 예를 들면, 용액, 겔, 고체, 반죽 무수 생성물, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구 또는 이온형(리포좀) 및 비이온형의 소낭 분산제의 형태인 것이거나, 크림, 스킨, 로션, 파우더, 연고, 스프레이 또는 콘실 스틱의 형태로 제공될 수 있 다. 또한 포말(foam)의 형태로 또는 압축된 추진제를 더 함유한 에어로졸 조성물의 형태로도 사용될 수 있다. 이들 조성물은 당해 분야의 통상적인 방법에 따라 제조될 수 있다. In the present invention, the external preparation may be formulated by containing a cosmetically or dermatologically acceptable medium or base. These are all formulations suitable for topical application, such as solutions, gels, solids, pasty anhydrous products, emulsions obtained by dispersing an oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or ionic forms (liposomes) and It may be in the form of an ionic follicular dispersant, or may be provided in the form of a cream, toner, lotion, powder, ointment, spray or conceal stick. It can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant. These compositions can be prepared according to conventional methods in the art.
또한, 상기 외용제는 지방 물질, 유기용매, 용해제, 농축제, 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제, 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질소낭 또는 화장품에 통상적으로 사용되는 임의의 다른 성분과 같은 화장품학 또는 피부과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 상기 보조제는 화장품학 또는 피부과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다.In addition, the external preparations include fatty substances, organic solvents, solubilizers, thickeners, gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers , fillers, sequestering agents, chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredient commonly used in cosmetics; or It may contain adjuvants commonly used in the field of dermatology. The adjuvant may be introduced in an amount generally used in the field of cosmetology or dermatology.
또한, 상기 외용제는 효과를 증가시키기 위하여 피부 흡수 촉진 물질을 함유할 수 있다. 또한, 상기 외용제는 상기 추출물 외에 본 발명의 목적을 손상시키지 않는 범위 내에서, 바람직하게는 상기 효과에 상승 효과를 줄 수 있는 다른 성분들을 함유할 수 있다.
In addition, the external preparation may contain a substance that promotes skin absorption in order to increase the effect. In addition, the external preparation may contain, in addition to the extract, other components capable of giving a synergistic effect to the above effect, preferably within a range not impairing the object of the present invention.
본 발명의 또 다른 구현 예에 따르면, 본 발명의 약학적 조성물을 목적하는 개체에 약학적 유효량으로 투여하는 단계를 포함하는, 염증성 질환의 예방 또는 치료 방법에 관한 것이다.According to another embodiment of the present invention, it relates to a method for preventing or treating inflammatory diseases, comprising administering the pharmaceutical composition of the present invention in a pharmaceutically effective amount to a target subject.
본 발명에서 “개체”란, 염증 질환 또는 피부 질환의 예방 또는 치료가 필요한 개체로서, 포유동물 및 비-포유동물을 모두 포함할 수 있다. 여기서, 상기 포유동물의 예로는 인간, 비-인간 영장류, 예컨대 침팬지, 다른 유인원 또는 원숭이 종; 축산 동물, 예컨대 소, 말, 양, 염소, 돼지; 사육 동물, 예컨대 토끼, 개 또는 고양이; 실험 동물, 예를 들어 설치류, 예컨대 래트, 마우스 또는 기니아 피그 등을 포함할 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the term "individual" is an individual in need of prevention or treatment of an inflammatory disease or skin disease, and may include both mammals and non-mammals. Here, examples of the mammal include humans, non-human primates such as chimpanzees, other apes or monkey species; livestock animals such as cattle, horses, sheep, goats, pigs; domesticated animals such as rabbits, dogs or cats; Laboratory animals, such as rodents, such as rats, mice, or guinea pigs, may be included, but are not limited thereto.
본 발명에서 “투여”란, 임의의 적절한 방법으로 개체에게 본 발명의 유효성분을 도입하는 과정을 의미하는 것으로서, 본 발명의 상기 치료 방법에서 투여 방법은 피부를 통해 투여될 수 있으나, 이에 제한되지는 않는다.In the present invention, "administration" refers to a process of introducing the active ingredient of the present invention into a subject by any suitable method, and in the treatment method of the present invention, the administration method may be administered through the skin, but is not limited thereto. does not
본 발명의 목적상, 목적하는 개체에 대한 구체적인 약학적 유효량은 달성하고자 하는 반응의 종류와 정도, 경우에 따라 다른 제제가 사용되는지의 여부를 비롯한 구체적 상기 유효성분을 포함하는 조성물, 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 상기 유효성분을 포함하는 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다.For the purpose of the present invention, the specific pharmaceutically effective amount for the target subject is the type and degree of response to be achieved, the composition containing the specific active ingredient, including whether other agents are used, depending on the case, the patient's age, Body weight, general health condition, sex and diet, administration time, route of administration, and secretion rate of the composition containing the active ingredient, treatment period, various factors including drugs used together with or concurrently used with the specific composition, and well known in the medical field It is preferable to apply differently according to similar factors.
본 발명에서, 생략된 나머지 기재들은 앞서 기재된 약학적 조성물의 기재와 마찬가지로 해석될 수 있다.
In the present invention, the remaining descriptions omitted can be interpreted in the same way as the description of the pharmaceutical composition described above.
본 발명의 다른 구현 예에 따르면, 본 발명의 조성물은 화장료 조성물인 것일 수 있다. 상기 화장료 조성물은 피부 개선용 화장료 조성물일 수 있다.According to another embodiment of the present invention, the composition of the present invention may be a cosmetic composition. The cosmetic composition may be a cosmetic composition for skin improvement.
본 발명에서, 상기 "피부 개선"은 피부의 내재적 요인 또는 외인적인 요인에 의하여 유발되는 피부의 손상을 치료, 경감, 완화시키는 과정 또는 그의 효과 등을 포괄적으로 의미하는 것으로, 보다 상세하게는 피부 미백, 주름 개선, 탄력 증진, 피부 재생, 피부 보습, 노화 방지, 피부 자극 완화, 여드름 개선 및 아토피 개선 효과에서 선택된 하나 이상인 것을 포함할 수 있고, 상기 손상은 자외선, 염증 및 활성산소에서 선택된 어느 하나 이상에서 선택된 것일 수 있다.In the present invention, the "skin improvement" comprehensively means the process of treating, reducing, alleviating damage to the skin caused by intrinsic or extrinsic factors of the skin, or its effect, and more specifically, skin whitening. , Wrinkle improvement, elasticity enhancement, skin regeneration, skin moisturizing, anti-aging, skin irritation relief, acne improvement and atopy may include one or more selected from the effects, wherein the damage is any one or more selected from ultraviolet rays, inflammation and active oxygen may be selected from
본 발명의 화장품은 유화제, 보존제, 용매, 점증제, 보습제, 향료, 생리 활성 성분 및 방부제로 이루어진 군으로부터 선택되는 하나 이상을 포함하는 것일 수 있다. The cosmetic of the present invention may contain one or more selected from the group consisting of an emulsifier, a preservative, a solvent, a thickener, a moisturizer, a fragrance, a physiologically active ingredient, and a preservative.
본 발명에서, 상기 유화제는 폴리올을 포함하는 것일 수 있고, 상기 폴리올은 2개 이상의 수산화기를 가지고 탄소수 3 내지 8의 지방족 폴리올인 것일 수 있다. 상기 폴리올(polyol)은 같은자리 디올(Geminal diol), 비시널 디올(Vicinal diol), 1,3-디올, 1,4-디올, 1,5-디올 또는 트리올(Triol)인 것일 수 있고, 글리세린(Glycerol, Glycerine), 부틸렌글리콜(Butanediol), 프로필렌글리콜(Propylene glycol), 소르비톨(Sorbitol), 펜타에리트리톨(Pentaerythritol) 및 자일리톨(Xylitol)에서 선택된 어느 하나 이상인 것일 수 있다.In the present invention, the emulsifier may include a polyol, and the polyol may be an aliphatic polyol having 3 to 8 carbon atoms and having two or more hydroxyl groups. The polyol may be geminal diol, vicinal diol, 1,3-diol, 1,4-diol, 1,5-diol or triol, It may be at least one selected from glycerol, glycerine, butanediol, propylene glycol, sorbitol, pentaerythritol, and xylitol.
본 발명의 일 실시예에 따른 화장료 조성물은, 글리세린, 부틸렌글리콜, 프로필렌글리콜, 폴리옥시에틸렌 경화피마자유, 에탄올, 트리에탄올아민, 밀납, 폴리솔베이트 60, 솔비탄 세스퀴올레이트, 유동 파라핀, 소르비탄 스테아레이트, 친유형 모노스테아린산 글리세린, 스테아린산, 글리세릴스테아레이트/피이지-400 스테아레이트, 카르복시폴리머, 시토스테롤, 폴리에틸렌 글리콜, 세라마이드, 스테아르산, 콜레스테롤, 디세틸포스페이트, 마카다미아 오일, 카르복시비닐폴리머, 신탄검, 잔탄검, 소이빈포스포리피드, 하이드록시에틸셀룰로오즈 및 히아루론산염으로 이루어진 군에서 선택된 1종 이상을 더 포함하는 것일 수 있고, 바람직하게는 상기 군에서 선택된 3종 이상을 더 포함하는 것일 수 있고, 더욱 바람직하게는 상기 군에서 선택된 4종 이상을 더 포함하는 것일 수 있는데, 상기 구성의 조합을 통하여 상기 축합중합체가 화장료 조성물에 잘 혼합될 수 있고, 그 결과 본 발명의 화장료 조성물은 현저히 뛰어난 피부 개선 효과를 가질 수 있다. The cosmetic composition according to an embodiment of the present invention includes glycerin, butylene glycol, propylene glycol, polyoxyethylene hydrogenated castor oil, ethanol, triethanolamine, beeswax,
본 발명의 상기 락토페린 유도체 100 중량부에 대하여, 상기 글리세린은 400 내지 800 중량부, 상기 부틸렌글리콜은 200 내지 600 중량부, 상기 프로필렌글리콜은 100 내지 300 중량부 및 상기 트리에탄올아민은 5 내지 30 중량부인 것일 수 있다.Based on 100 parts by weight of the lactoferrin derivative of the present invention, the glycerin is 400 to 800 parts by weight, the butylene glycol is 200 to 600 parts by weight, the propylene glycol is 100 to 300 parts by weight, and the triethanolamine is 5 to 30 parts by weight may be denying
본 발명의 상기 락토페린 유도체 100 중량부에 대하여, 상기 글리세린은 400 내지 800 중량부, 상기 부틸렌글리콜은 200 내지 600 중량부, 상기 프로필렌글리콜은 100 내지 300 중량부 및 상기 트리에탄올아민은 5 내지 30 중량부인 것일 수 있다.Based on 100 parts by weight of the lactoferrin derivative of the present invention, the glycerin is 400 to 800 parts by weight, the butylene glycol is 200 to 600 parts by weight, the propylene glycol is 100 to 300 parts by weight, and the triethanolamine is 5 to 30 parts by weight may be denying
본 발명의 상기 락토페린 유도체 100 중량부에 대하여, 상기 밀납은 100 내지 300 중량부, 상기 폴리솔베이트 60은 50 내지 400 중량부, 상기 솔비탄 세스퀴올레이트는 50 내지 150 중량부, 상기 소르비탄 스테아레이트는 100 내지 300 중량부, 친유형 모노스테아린산 글리세린은 50 내지 150 중량부, 상기 스테아린산은 150 내지 400 중량부, 상기 글리세릴스테아레이트/피이지-400 스테아레이트는 100 내지 300 중량부, 상기 프로필렌글리콜은 300 내지 800 중량부, 상기 카르복시폴리머는 100 내지 30 중량부 및 상기 트리에탄올아민은 20 내지 60 중량부인 것일 수 있다.Based on 100 parts by weight of the lactoferrin derivative of the present invention, the beeswax is 100 to 300 parts by weight, the
그 밖에 본 발명의 화장료 조성물은 화장료 조성물의 제조에 통상적으로 사용하는 용매나, 적절한 담체, 부형제 또는 희석제를 더 포함할 수 있고, 조성물은 고형, 젤형, 액상형, 에어로졸 형 등의 제형인 것일 수 있다.In addition, the cosmetic composition of the present invention may further include a solvent commonly used in the manufacture of a cosmetic composition, or an appropriate carrier, excipient, or diluent, and the composition may be in a solid, gel, liquid, or aerosol type formulation. .
본 발명에서, 상기 화장료 조성물은 특별히 제한되지는 않으나 화장수, 미스트, 로션, 에멀젼, 세럼, 에센스, 영양 크림, 나이트 크림, 연고, 팩, 패치, 마스크 시트, 연고, 앰플, 헤어 제품, 향수 제품, 비누, 클렌징 폼, 클렌징 크림, 클렌징 오일, 클렌징 워터, 손세정제, 두피세정제, 헤어린스, 바디워시, 미용 목욕물 첨가제 및 미용 제품 중에서 선택된 어느 하나 이상인 것일 수 있다.
In the present invention, the cosmetic composition is not particularly limited, but lotion, mist, lotion, emulsion, serum, essence, nourishing cream, night cream, ointment, pack, patch, mask sheet, ointment, ampoule, hair product, perfume product, It may be at least one selected from soap, cleansing foam, cleansing cream, cleansing oil, cleansing water, hand sanitizer, scalp cleaner, hair rinse, body wash, beauty bath water additives, and beauty products.
이하, 본 발명의 실시예를 통해 본 발명을 더욱 상술하나 하기 실시예에 의해 본 발명이 제한되지 아니함은 자명하다.
Hereinafter, the present invention is further detailed through examples of the present invention, but it is obvious that the present invention is not limited by the following examples.
<실험예 1> N-Hyaluronoyl Lactoferrin(NHL)의 제조<Experimental Example 1> Preparation of N-Hyaluronoyl Lactoferrin (NHL)
도 1에 따른 NHL을 제조하였다. 구체적으로는 Hyalurononic acid에 커플링 시약(coupling reagent)인 EDC(1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide)와 NHS(N-Hydroxysuccinimide)를 넣어 교반하고 Lactoferrin을 첨가하였다. 정제방법으로는 Acetone의 최종농도가 50 ~ 90%가 되도록 Acetone을 첨가하여 침전한 후 70%, 80%, 90%, 95%, 100% Ethanol을 이용하여 건조하였다.
An NHL according to FIG. 1 was prepared. Specifically, EDC (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide) and NHS (N-Hydroxysuccinimide), which are coupling reagents, were added to hyalurononic acid, stirred, and lactoferrin was added. As a purification method, after precipitating by adding acetone to a final concentration of 50 to 90%, drying was performed using 70%, 80%, 90%, 95%, and 100% Ethanol.
<실험예 2> oxHA-lactoferrin(oxi-HLF)의 제조<Experimental Example 2> Preparation of oxHA-lactoferrin (oxi-HLF)
도 2에 따른 oxi-HLF를 제조하였다. 구체적으로는 Hyalurononic acid에 산화제인 NaIO4를 첨가하여 산화시키고 Latoferrin을 첨가한 후 상온에서 2~5일 교반하였다. 정제방법으로는 Acetone의 최종농도가 50-90%가 되도록 Acetone을 첨가하여 침전한 후 70%, 80%, 90%, 95%, 100% Ethanol을 이용하여 건조하였다.
Oxi-HLF was prepared according to FIG. 2 . Specifically, NaIO 4 , an oxidizing agent, was added to hyalurononic acid to oxidize it, and after adding Latoferrin, the mixture was stirred at room temperature for 2 to 5 days. As a purification method, after precipitating by adding acetone to a final concentration of 50-90%, drying was performed using 70%, 80%, 90%, 95%, and 100% Ethanol.
<실험예 3> 세포 독성 실험<Experimental Example 3> Cytotoxicity test
케라틴 세포주 HaCaT을 24 well plate에 4X104 cells/well의 농도로 분주하여 24시간 동안 37℃, 5% CO2조건으로 항온배양 하였다. 무혈청배지에 합성-LF, HA, NLF를 농도별(250, 1000 μg/ml)로 처리하여 24시간 동안 배양하였다. 다음으로 PBS로 세척 후 100μl의 MTT(3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazoliumbromide, SIGMA, USA) (5mg/ml in DPBS)를 각 well에 분주하여 37 ℃에서 3시간 동안 반응하였다. MTT 제거 후 100μL의 DMSO(Dimethyl sulfoxide, SIGMA, USA)를 첨가하여 15분 동안 반응시킨 후 MTT가 환원되어 생성된 MTT formazan 흡광도를 ELISA를 이용하여 570nm에서 측정하였고, 그 결과를 도 3에 나타내었다. The keratin cell line HaCaT was dispensed in a 24 well plate at a concentration of 4X10 4 cells/well and incubated for 24 hours at 37°C and 5% CO 2 conditions. The serum-free medium was treated with synthetic-LF, HA, and NLF at different concentrations (250 and 1000 μg/ml) and cultured for 24 hours. Next, after washing with PBS, 100μl of MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazoliumbromide, SIGMA, USA) (5mg/ml in DPBS) was dispensed into each well and incubated at 37 °C. After removing MTT, 100 μL of DMSO (Dimethyl sulfoxide, SIGMA, USA) was added and reacted for 15 minutes. is shown in Figure 3.
도 3에 나타난 것처럼, HaCat 세포는 저농도에서 고농도까지 처리한 시료에 의한 세포수의 감소는 관찰되지 않았으며, 세포들의 현미경적인 관찰에서도 별다른 변화가 관찰되지 않았다.
As shown in FIG. 3, HaCat cells were not observed to decrease in the number of cells in samples treated from low concentration to high concentration, and no significant change was observed in microscopic observation of the cells.
<실험예 4> NHL 및 oxi-HLF의 처리 농도에 따른 UVB에 의한 세포 사멸 억제 효과 확인<Experimental Example 4> Confirmation of cell death inhibitory effect by UVB according to treatment concentrations of NHL and oxi-HLF
HaCaT 세포를 24 well plate에 4X104 cells/well의 농도로 분주하여 24시간 동안 37℃, 5% CO2조건으로 항온배양 하였다. 배양 배지를 제거한 후 5% BSA(SIGMA, USA)가 첨가된 무혈청 저농도 포도당(free serum low glucose) DMEM(Gibco, USA)배지에 대조군으로 DMSO를 첨가하고, 실험 및 비교군으로 시료(DMSO, LF, HA, NLF, oxi-HLF)를 각각 농도별 (0, 31, 63, 125, 250, 500, 1000 μg/ml)로 첨가하여 세포에 처리하고 10시간 동안 37℃, 5% 배양기에서 배양하였다. CL-1000 ultraviolet crosslinker를 이용하여 30mJ/cm2 UVB를 조사하고 CO2 인큐베이터에 12시간 배양한 후 배지를 제거하고 각 well에 100μl의 MTT(5mg/ml in DPBS)를 분주하여 37℃에서 3시간 동안 반응하였다. MTT 제거 후 100μL의 DMSO(Dimethyl sulfoxide, SIGMA, USA)를 첨가하여 15분 동안 반응시킨 후 MTT가 환원되어 생성된 MTT formazan 570nm 흡광도에 대하여, ELISA를 이용하여 측정하여, 그 결과를 도 4에 나타내었다. 이 흡광도는 MTT가 세포에 의해서 환원된 양을 나타내며, 따라서 각 웰에 존재하는 생존 세포수와 비례한다.HaCaT cells were dispensed in a 24 well plate at a concentration of 4X10 4 cells/well and incubated for 24 hours at 37°C and 5% CO 2 conditions. After removing the culture medium, DMSO was added as a control to serum-free low glucose DMEM (Gibco, USA) medium to which 5% BSA (SIGMA, USA) was added, and samples (DMSO, LF, HA, NLF, and oxi-HLF) were added at concentrations (0, 31, 63, 125, 250, 500, and 1000 μg/ml) to the cells and cultured in a 37°C, 5% incubator for 10 hours. did Irradiate 30mJ/cm 2 UVB using CL-1000 ultraviolet crosslinker, incubate in a CO2 incubator for 12 hours, remove the medium, and dispense 100μl of MTT (5mg/ml in DPBS) into each well for 3 hours at 37℃. reacted. After removing MTT, 100 μL of DMSO (Dimethyl sulfoxide, SIGMA, USA) was added and reacted for 15 minutes. Then, the absorbance at 570 nm of MTT formazan produced by reducing MTT was measured using ELISA, and the results are shown in FIG. 4 was This absorbance indicates the amount of MTT reduced by the cells and is therefore proportional to the number of viable cells present in each well.
도 4에 나타난 것처럼, 측정시 공시료는 DMSO로 하였고 생존율(%)은 (시료처리군의 흡광도/대조군의 흡광도)x100으로 계산하였다. 그 결과, 대조군인 DMSO에 비교하여 LF, NLF에서 UVB에 의한 세포 사멸을 억제하였다.
As shown in Figure 4, the blank sample was DMSO at the time of measurement, and the survival rate (%) was calculated as (absorbance of sample treatment group / absorbance of control group) x 100. As a result, UVB-induced apoptosis was inhibited in LF and NLF compared to the control, DMSO.
<실험예 5> NHL 및 oxi-HLF의 처리 농도에 따른 활성산소 변화<Experimental Example 5> Changes in reactive oxygen species according to treatment concentrations of NHL and oxi-HLF
자외선이 피부를 침투하게 되면 활성산소종(reactive oxygen species; ROS)이 형성되어 피부세포를 사멸시키며 피부노화가 진행된다. HaCaT 세포를 96 well black plate에 4X104 cells/well의 농도로 분주하여 37℃, 5% CO2 조건으로 24시간 동안 항온 배양하였다. 배양 배지를 제거한 후 5% BSA(SIGMA, USA)가 첨가된 무혈청 저농도 포도당(free serum low glucose) DMEM(Gibco, USA)배지에 실험 및 비교군으로 시료(DMSO, LF, HA, NLF, oxi-HLF)를 각각 농도별(500, 1000 μg/ml)로 첨가하여 세포에 처리하고 10시간 동안 37 ℃, 5% 배양기에서 배양하였다. CL-1000 ultraviolet crosslinker를 이용하여 30mJ/cm2 UVB를 조사하고 CO2 인큐베이터에 2시간 동안 배양한 후 배지를 제거하고 PBS로 세척한 후 각 well에 50uM의 DCFDA(dichlorodihydrofluorescein diacetate)를 분주하여 37℃에서 20분간 반응시켰다. DCFDA는 ROS에 의해 형광성이 높은 DCF로 산화되며, 이러한 형광 광도의 변화를 ELISA를 이용하여 485nm 및 530nm에서 측정하여, 그 결과를 도 5에 나타내었다.When UV rays penetrate the skin, reactive oxygen species (ROS) are formed to kill skin cells and cause skin aging. HaCaT cells were dispensed in a 96 well black plate at a concentration of 4X10 4 cells/well, and incubated at 37°C, 5% CO 2 for 24 hours. After removing the culture medium, samples (DMSO, LF, HA, NLF, oxi -HLF) was added at each concentration (500, 1000 μg/ml) to treat the cells and incubated in a 37° C., 5% incubator for 10 hours. After irradiating 30mJ/cm 2 UVB using a CL-1000 ultraviolet crosslinker, incubating in a CO 2 incubator for 2 hours, removing the medium, washing with PBS, and dispensing 50uM DCFDA (dichlorodihydrofluorescein diacetate) into each well and heating it to 37°C. reacted for 20 minutes. DCFDA is oxidized to highly fluorescent DCF by ROS, and the change in fluorescence intensity was measured using ELISA at 485 nm and 530 nm, and the results are shown in FIG. 5 .
도 5에 나타난 것처럼, LF, NLF, oxi-HLF를 처리한 세포에서 ROS 제거 효과가 비례하여 증가하는 것을 확인하였다.
As shown in FIG. 5 , it was confirmed that the ROS removal effect increased proportionally in the cells treated with LF, NLF, and oxi-HLF.
<실험예 6> NHL 및 oxi-HLF의 처리에 따른 세포의 염증 반응 확인<Experimental Example 6> Confirmation of inflammatory response of cells according to treatment of NHL and oxi-HLF
NHL 및 oxi-HLF의 처리에 따른 세포의 염증 억제 효과를 확인하기 위하여, 콜라겐분해효소 MPP-1 및 종양괴사인자 TNF-α의 유전자발현을 확인하였다. 구체적으로는 HaCaT세포를 6 well plate에 2X105 cells/well의 농도로 분주하여 37℃, 5% CO2 조건으로 24시간 동안 항온 배양하였다. 배지를 제거한 후 5% BSA(SIGMA, USA)가 첨가된 무혈청 저농도 포도당(free serum low glucose) DMEM(Gibco, USA)배지에 실험 및 비교군으로 시료(DMSO, LF, HA, NLF, oxi-HLF)를 첨가하여 세포에 처리하고 10시간 동안 37℃, 5% 배양기에서 배양하였다. CL-1000 ultraviolet crosslinker를 이용하여 30 mJ/cm2 UVB를 조사하고 CO2 인큐베이터에 12시간 동안 추가 배양한 후, 멸균된 PBS로 2회 세척 후 트리졸 시약(TRIzol reagent, Life Technologies, Rockville, MD, USA)으로 전체 RNA를 추출하였다. RNA를 정량한후, cDNA는 추출된 1μg의 RNA로 합성하였다. 역전사효소키트를 사용하여 각 cDNA를 제조하여 실시간 PCR에 사용하였다. 특정 유전자에 대한 동량의 cDNA 및 프라이머를 SYBR-Green(Bio-Rad, Richmond, CA)와 혼합하고 실시간 PCR 기구를 사용하여 증폭시켰다. 여기서 β-actin은 유전자들을 검지하기 위한 유전자로 사용되었고, 각 유전자에 대한 정방향 프라이머(forward primer; F) 및 역방향 프라이머(reverse primer; R)는 하기 표 1에 나타난 서열에 해당하는 것을 사용하였다.
In order to confirm the effect of inhibiting cell inflammation according to the treatment of NHL and oxi-HLF, gene expression of the collagenase MPP-1 and the tumor necrosis factor TNF-α was confirmed. Specifically, HaCaT cells were dispensed in a 6-well plate at a concentration of 2X10 5 cells/well and incubated at 37° C. under 5% CO 2 conditions for 24 hours. After removing the medium, samples (DMSO, LF, HA, NLF, oxi- HLF) was added to treat the cells and cultured in a 37°C, 5% incubator for 10 hours. After irradiating 30 mJ/cm 2 UVB using a CL-1000 ultraviolet crosslinker, incubating in a CO 2 incubator for 12 hours, washing twice with sterilized PBS and using TRIzol reagent (Life Technologies, Rockville, MD) , USA) to extract total RNA. After RNA was quantified, cDNA was synthesized from 1 μg of extracted RNA. Each cDNA was prepared using a reverse transcriptase kit and used for real-time PCR. Equal amounts of cDNA and primers for specific genes were mixed with SYBR-Green (Bio-Rad, Richmond, Calif.) and amplified using a real-time PCR instrument. Here, β-actin was used as a gene for detecting genes, and forward primers (F) and reverse primers (R) for each gene corresponding to the sequences shown in Table 1 below were used.
열 사이클 조건은 95℃에서 10분, 95℃에서 20초, 65℃에서 30초, 72℃에서 20초 동안 40 사이클만큼 증폭였고, 각 샘플의 CT(cycle of threshold)를 측정하였다. 미지 샘플의 유전자 발현 수준은 상대 CT 정량법(comparative CT method)을 사용하여 정량하였다. ΔCT는 하기 식 1과 같이 계산하였고, 발현 시 상대적 폴드-변화는 하기 식 2 및 3과 같이 계산하였으며, MMP-1 발현에 대한 결과를 도 6에 나타내었고, TNF-α 발현에 대한 결과를 및 도 7에 나타내었다. Thermal cycle conditions were amplification by 40 cycles of 95°C for 10 minutes, 95°C for 20 seconds, 65°C for 30 seconds, and 72°C for 20 seconds, and the CT (cycle of threshold) of each sample was measured. Gene expression levels of unknown samples were quantified using the comparative CT method. ΔCT was calculated as in Equation 1 below, and the relative fold-change upon expression was calculated as in Equations 2 and 3 below, and the results for MMP-1 expression were shown in Figure 6, and the results for TNF-α expression and 7 shows.
[식 1][Equation 1]
ΔCT = CT(표적 유전자) - CT (내인성 참조 유전자, β-actin)ΔCT = CT (target gene) - CT (endogenous reference gene, β-actin)
[식 2][Equation 2]
ΔΔCT = CTtreatment - CTcontrol ΔΔCT = CT treatment - CT control
[식 3][Equation 3]
(상대적 폴드-변화) = 2-ΔΔCT (relative fold-change) = 2 -ΔΔCT
도 6 및 도 7에 나타난 것처럼, 타입I 콜라겐(collagen-I)을 분해하는 효소인 MMP-1(Matrix metalloproteinase-1)과 종양괴사인자 TNF-α의 유전자 발현이 LF, NLF, oxi-HLF에 의하여 감소되었음을 확인하였다.
As shown in FIGS. 6 and 7 , gene expression of matrix metalloproteinase-1 (MMP-1), an enzyme that degrades type I collagen, and tumor necrosis factor TNF-α, were found in LF, NLF, and oxi-HLF. It was confirmed that it was reduced by
<실험예 7> NHL 및 oxi-HLF의 처리 시 세포의 미백에 미치는 영향<Experimental Example 7> Effect on cell whitening when treated with NHL and oxi-HLF
B16F10 세포를 6 well plate에 2X104 cells/well의 농도로 분주하여 37℃, 5% CO2 조건으로 24시간 동안 항온 배양하였다. DMSO처리 대조군, DMSO와 a-MSH을 200uM 첨가한 대조군 그리고 α-MSH 200uM과 각 시료(LF, HA, NLF, oxi-HLF)를 처리하여 48시간 동안 배양하였다. PBS(pH 7.4)으로 세척 후 세포를 회수하여 원심분리 하여 세포 침전물을 얻었다. 다음으로 10% DMSO가 첨가된 1N NaOH 용액 130μL를 첨가하고 80°C에서 1시간 용해시킨 후 405nm에서 흡광도를 측정하여 도 8에 나타내었다. 이때 멜라닌(Melanin) 정량은 대조군의 Melanin 양에 대한 백분율로 계산하여 산출하였다. B16F10 cells were dispensed at a concentration of 2X10 4 cells/well in a 6-well plate and incubated at 37° C. under 5% CO 2 conditions for 24 hours. A DMSO-treated control group, a control group containing 200uM of DMSO and a-MSH, and 200uM of α-MSH were treated with each sample (LF, HA, NLF, and oxi-HLF) and cultured for 48 hours. After washing with PBS (pH 7.4), the cells were collected and centrifuged to obtain a cell precipitate. Next, 130 μL of 1N NaOH solution with 10% DMSO was added, dissolved at 80 ° C for 1 hour, and absorbance was measured at 405 nm, as shown in FIG. 8 . At this time, the amount of melanin (Melanin) was calculated by calculating as a percentage of the amount of melanin in the control group.
도 8에 나타난 것처럼, Melanin 양은 LF, NLF, oxi-HLF 처리군에서 대조군에 비해 유의적으로 줄어드는 것을 확인하였다.
As shown in FIG. 8, it was confirmed that the amount of melanin was significantly reduced in the LF, NLF, and oxi-HLF treated groups compared to the control group.
<제조예 1> NHL 및 oxi-HLF 유도체를 포함하는 화장수 제조<Preparation Example 1> Preparation of lotion containing NHL and oxi-HLF derivatives
상기 실험예 1 또는 2에서 제조된 NHL 또는 oxi-HLF 유도체를 함유한 화장수(스킨로션)를 하기의 표 2의 함량으로 1kg을 제조하였다.
1 kg of lotion (skin lotion) containing the NHL or oxi-HLF derivative prepared in Experimental Example 1 or 2 was prepared in the contents shown in Table 2 below.
구체적인 제조 방법으로는, 상기 표 2에서 11번 물질에 2, 3, 4, 8번 물질을 순서대로 반응용기에 투입하고 교반하여 용해시킨 후, 5번 물질을 60℃ 정도로 가열하여 용해시켰다. 다음으로 10번 물질을 반응용기에 투입하여 용해한 후 11번 물질에 투입하였다. 마지막으로 1, 6, 7, 9번 물질을 투입하여 충분히 교반시킨 뒤 25℃에서 3일간 숙성시켜 본 발명의 화장수를 제조하였다.
As a specific manufacturing method, materials No. 2, 3, 4, and 8 were added to the material No. 11 in Table 2 in order into the reaction vessel and stirred to dissolve, and then material No. 5 was dissolved by heating to about 60 ° C. Next, the material No. 10 was put into the reaction vessel to dissolve, and then the material No. 11 was added. Finally, substances 1, 6, 7, and 9 were added, sufficiently stirred, and aged at 25° C. for 3 days to prepare the lotion of the present invention.
<제조예 2> NHL oxi-HLF 유도체를 포함하는 영양 로션 제조<Preparation Example 2> Preparation of nutritional lotion containing NHL oxi-HLF derivative
상기 실험예 1 및 2에서 제조된 NHL 또는 oxi-HLF 유도체를 함유한 하이드로좀 영양로션을 하기의 표 2의 함량으로 1kg을 제조하였다.
1 kg of the hydrosome nutrient lotion containing the NHL or oxi-HLF derivative prepared in Experimental Examples 1 and 2 was prepared with the contents shown in Table 2 below.
구체적인 제조 방법으로는, 상기 표 3에서 번호 10, 11, 13, 16번 물질을 혼합 교반 하면서 80 ~ 85℃ 사이로 가열하여 제조부에 투입한 후 유화기를 작용시키고 2, 3, 4, 5, 6, 7, 8, 9, 12번 물질을 80 ~ 85℃ 사이로 가열 용해한 후 유화시켰다. 유화가 끝나면 교반기를 이용하여 교반하면서 50℃까지 냉각한 뒤 15번 물질을 투입하고 45℃까지 냉각한 뒤 14번 물질을 투입하고 35℃에서 1번 물질을 투입하여 25℃까지 냉각한 뒤 25℃에서 3일간 숙성시켜 본 발명의 영양로션을 제조하였다.
As a specific manufacturing method, materials No. 10, 11, 13, and 16 in Table 3 are heated between 80 and 85 ° C. while mixing and stirring, and then introduced into the manufacturing unit, followed by operation of an emulsifier and 2, 3, 4, 5, 6 , Nos. 7, 8, 9, and 12 were heated and dissolved at 80 to 85 ° C and then emulsified. After emulsification is finished, cool to 50℃ while stirring using a stirrer, add material No. 15, cool to 45℃, add material No. 14, add material No. 1 at 35℃, cool to 25℃, and cool to 25℃. The nutritional lotion of the present invention was prepared by aging for 3 days.
<제조예 3> NHL oxi-HLF 유도체를 포함하는를 포함하는 영양 세럼 제조<Preparation Example 3> Preparation of nutritional serum containing an NHL oxi-HLF derivative
상기 실험예 1 및 2에서 제조된 NHL 또는 oxi-HLF 유도체를 함유한 하이드로좀 영양세럼을 표 4의 함량으로 1kg을 제조하였다.
1 kg of the hydrosome nutritional serum containing the NHL or oxi-HLF derivatives prepared in Experimental Examples 1 and 2 was prepared in the contents shown in Table 4.
구체적인 제조 방법으로는, 상기 표 4에서 2, 3, 5번 물질을 혼합 교반 하면서 40 ~ 45℃ 사이로 가열하여 제조부에 투입한 후 유화기를 작용시키고 4, 6, 7번 물질을 제조부에 투입하고 유화시켰다. 유화가 끝나면 교반기를 이용하여 교반 하면서 35℃까지 냉각하고 1번 물질을 투입하여 25℃까지 냉각한 뒤 25℃에서 3일간 숙성시켜 본 발명의 영양 세럼을 제조하였다.
As a specific manufacturing method, materials No. 2, 3, and 5 in Table 4 are heated between 40 and 45 ° C. while mixing and stirring, and then introduced into the manufacturing unit, and then the emulsifier is operated and materials No. 4, 6, and 7 are introduced into the production unit. and emulsified. After emulsification was completed, the mixture was cooled to 35 ° C. while stirring using a stirrer, and after cooling to 25 ° C., material No. 1 was added and aged at 25 ° C. for 3 days to prepare the nutritional serum of the present invention.
<제조예 4> NHL 유도체를 포함하는 에센스 제조<Preparation Example 4> Preparation of essence containing NHL derivatives
상기 실험예 1 및 2에서 제조된 NHL 및 oxi-HLF 유도체를 함유한 하이드로좀 에센스를 하기의 표 5의 함량으로 1kg을 제조하였다.
1 kg of the hydrosome essence containing the NHL and oxi-HLF derivatives prepared in Experimental Examples 1 and 2 was prepared in the contents shown in Table 5 below.
구체적인 제조 방법으로는, 상기 표 5의 2, 3, 4, 5 및 6번 물질을 일정한 온도에서 균질화하여 비이온계 양친매성 지질을 제조하였다. 이 비이온계 양친매성 지질과 1, 7, 8 및 14번 물질을 혼합하고 일정한 온도에서 균질화하여 마이크로플루이다이져를 통과시키고 이어 9번 물질을 50 ~ 60℃로 가온하여 서서히 첨가하여 균질화한 후 다시 마이크로플루이다이져에 재차 통과시켰다. 그 후, 10, 11, 12, 13번 물질을 투입하여 분산시켜 안정화하고 25℃에서 3일간 숙성시켜 본 발명의 에센스를 제조하였다.
As a specific preparation method, materials 2, 3, 4, 5 and 6 in Table 5 were homogenized at a constant temperature to prepare nonionic amphiphilic lipids. The nonionic amphiphilic lipid and materials 1, 7, 8, and 14 were mixed and homogenized at a constant temperature to pass through a microfluidizer, followed by heating the material No. 9 to 50 ~ 60 ° C. After homogenization by gradually adding It was passed through the microfluidizer again. After that, materials No. 10, 11, 12, and 13 were added, dispersed, stabilized, and aged at 25° C. for 3 days to prepare the essence of the present invention.
상기와 같이, 제조된 화장료 조성물의 경우 피부 회복, 주름 개선, 미백 및 피부결 정돈 효과에 매우 뛰어난 것을 확인할 수 있었다.
As described above, in the case of the prepared cosmetic composition, it was confirmed that the skin recovery, wrinkle improvement, whitening and skin texture adjustment effects were very excellent.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수 있다. The above description of the present invention is for illustrative purposes, and those skilled in the art can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined form.
본 발명의 범위는 청구범위에 의하여 나타내어지며, 청구범위 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present invention is indicated by the claims, and all changes or modifications derived from the meaning and scope of the claims and equivalent concepts should be construed as being included in the scope of the present invention.
<110> LEE, Huisu <120> A composition containing lactoferrin derivative and manufacturing method thereof <130> P213190 <160> 12 <170> KoPatentIn 3.0 <210> 1 <211> 710 <212> PRT <213> Homo sapiens <400> 1 Met Lys Leu Val Phe Leu Val Leu Leu Phe Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Gly Arg Arg Arg Ser Val Gln Trp Cys Ala Val Ser Gln 20 25 30 Pro Glu Ala Thr Lys Cys Phe Gln Trp Gln Arg Asn Met Arg Lys Val 35 40 45 Arg Gly Pro Pro Val Ser Cys Ile Lys Arg Asp Ser Pro Ile Gln Cys 50 55 60 Ile Gln Ala Ile Ala Glu Asn Arg Ala Asp Ala Val Thr Leu Asp Gly 65 70 75 80 Gly Phe Ile Tyr Glu Ala Gly Leu Ala Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Val Tyr Gly Thr Glu Arg Gln Pro Arg Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Gly Ser Phe Gln Leu Asn Glu Leu 115 120 125 Gln Gly Leu Lys Ser Cys His Thr Gly Leu Arg Arg Thr Ala Gly Trp 130 135 140 Asn Val Pro Ile Gly Thr Leu Arg Pro Phe Leu Asn Trp Thr Gly Pro 145 150 155 160 Pro Glu Pro Ile Glu Ala Ala Val Ala Arg Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Gly Ala Asp Lys Gly Gln Phe Pro Asn Leu Cys Arg Leu Cys 180 185 190 Ala Gly Thr Gly Glu Asn Lys Cys Ala Phe Ser Ser Gln Glu Pro Tyr 195 200 205 Phe Ser Tyr Ser Gly Ala Phe Lys Cys Leu Arg Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Ile Arg Glu Ser Thr Val Phe Glu Asp Leu Ser Asp Glu 225 230 235 240 Ala Glu Arg Asp Glu Tyr Glu Leu Leu Cys Pro Asp Asn Thr Arg Lys 245 250 255 Pro Val Asp Lys Phe Lys Asp Cys His Leu Ala Arg Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asn Gly Lys Glu Asp Ala Ile Trp Asn 275 280 285 Leu Leu Arg Gln Ala Gln Glu Lys Phe Gly Lys Asp Lys Ser Pro Lys 290 295 300 Phe Gln Leu Phe Gly Ser Pro Ser Gly Gln Lys Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Ile Gly Phe Ser Arg Val Pro Pro Arg Ile Asp Ser Gly 325 330 335 Leu Tyr Leu Gly Ser Gly Tyr Phe Thr Ala Ile Gln Asn Leu Arg Lys 340 345 350 Ser Glu Glu Glu Val Ala Ala Arg Arg Ala Arg Val Val Trp Cys Ala 355 360 365 Val Gly Glu Gln Glu Leu Arg Lys Cys Asn Gln Trp Ser Gly Leu Ser 370 375 380 Glu Gly Ser Val Thr Cys Ser Ser Ala Ser Thr Thr Glu Asp Cys Ile 385 390 395 400 Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Met Ser Leu Asp Gly Gly 405 410 415 Tyr Val Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Leu Ala Glu 420 425 430 Asn Tyr Lys Ser Gln Gln Ser Ser Asp Pro Asp Pro Asn Cys Val Asp 435 440 445 Arg Pro Val Glu Gly Tyr Leu Ala Val Ala Val Val Arg Arg Ser Asp 450 455 460 Thr Ser Leu Thr Trp Asn Ser Val Lys Gly Lys Lys Ser Cys His Thr 465 470 475 480 Ala Val Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Leu Phe 485 490 495 Asn Gln Thr Gly Ser Cys Lys Phe Asp Glu Tyr Phe Ser Gln Ser Cys 500 505 510 Ala Pro Gly Ser Asp Pro Arg Ser Asn Leu Cys Ala Leu Cys Ile Gly 515 520 525 Asp Glu Gln Gly Glu Asn Lys Cys Val Pro Asn Ser Asn Glu Arg Tyr 530 535 540 Tyr Gly Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asn Ala Gly Asp 545 550 555 560 Val Ala Phe Val Lys Asp Val Thr Val Leu Gln Asn Thr Asp Gly Asn 565 570 575 Asn Asn Glu Ala Trp Ala Lys Asp Leu Lys Leu Ala Asp Phe Ala Leu 580 585 590 Leu Cys Leu Asp Gly Lys Arg Lys Pro Val Thr Glu Ala Arg Ser Cys 595 600 605 His Leu Ala Met Ala Pro Asn His Ala Val Val Ser Arg Met Asp Lys 610 615 620 Val Glu Arg Leu Lys Gln Val Leu Leu His Gln Gln Ala Lys Phe Gly 625 630 635 640 Arg Asn Gly Ser Asp Cys Pro Asp Lys Phe Cys Leu Phe Gln Ser Glu 645 650 655 Thr Lys Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Arg Leu 660 665 670 His Gly Lys Thr Thr Tyr Glu Lys Tyr Leu Gly Pro Gln Tyr Val Ala 675 680 685 Gly Ile Thr Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala 690 695 700 Cys Glu Phe Leu Arg Lys 705 710 <210> 2 <211> 708 <212> PRT <213> Bos taurus <400> 2 Met Lys Leu Phe Val Pro Ala Leu Leu Ser Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Ala Pro Arg Lys Asn Val Arg Trp Cys Thr Ile Ser Gln 20 25 30 Pro Glu Trp Phe Lys Cys Arg Arg Trp Gln Trp Arg Met Lys Lys Leu 35 40 45 Gly Ala Pro Ser Ile Thr Cys Val Arg Arg Ala Phe Ala Leu Glu Cys 50 55 60 Ile Arg Ala Ile Ala Glu Lys Lys Ala Asp Ala Val Thr Leu Asp Gly 65 70 75 80 Gly Met Val Phe Glu Ala Gly Arg Asp Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Ile Tyr Gly Thr Lys Glu Ser Pro Gln Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Ser Asn Phe Gln Leu Asp Gln Leu 115 120 125 Gln Gly Arg Lys Ser Cys His Thr Gly Leu Gly Arg Ser Ala Gly Trp 130 135 140 Ile Ile Pro Met Gly Ile Leu Arg Pro Tyr Leu Ser Trp Thr Glu Ser 145 150 155 160 Leu Glu Pro Leu Gln Gly Ala Val Ala Lys Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Cys Ile Asp Arg Gln Ala Tyr Pro Asn Leu Cys Gln Leu Cys 180 185 190 Lys Gly Glu Gly Glu Asn Gln Cys Ala Cys Ser Ser Arg Glu Pro Tyr 195 200 205 Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Gln Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Val Lys Glu Thr Thr Val Phe Glu Asn Leu Pro Glu Lys 225 230 235 240 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asn Asn Ser Arg Ala 245 250 255 Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Gln Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asp Gly Lys Glu Asp Leu Ile Trp Lys 275 280 285 Leu Leu Ser Lys Ala Gln Glu Lys Phe Gly Lys Asn Lys Ser Arg Ser 290 295 300 Phe Gln Leu Phe Gly Ser Pro Pro Gly Gln Arg Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Leu Gly Phe Leu Arg Ile Pro Ser Lys Val Asp Ser Ala 325 330 335 Leu Tyr Leu Gly Ser Arg Tyr Leu Thr Thr Leu Lys Asn Leu Arg Glu 340 345 350 Thr Ala Glu Glu Val Lys Ala Arg Tyr Thr Arg Val Val Trp Cys Ala 355 360 365 Val Gly Pro Glu Glu Gln Lys Lys Cys Gln Gln Trp Ser Gln Gln Ser 370 375 380 Gly Gln Asn Val Thr Cys Ala Thr Ala Ser Thr Thr Asp Asp Cys Ile 385 390 395 400 Val Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Asn Leu Asp Gly Gly 405 410 415 Tyr Ile Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Leu Ala Glu 420 425 430 Asn Arg Lys Ser Ser Lys His Ser Ser Leu Asp Cys Val Leu Arg Pro 435 440 445 Thr Glu Gly Tyr Leu Ala Val Ala Val Val Lys Lys Ala Asn Glu Gly 450 455 460 Leu Thr Trp Asn Ser Leu Lys Asp Lys Lys Ser Cys His Thr Ala Val 465 470 475 480 Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Ile Val Asn Gln 485 490 495 Thr Gly Ser Cys Ala Phe Asp Glu Phe Phe Ser Gln Ser Cys Ala Pro 500 505 510 Gly Ala Asp Pro Lys Ser Arg Leu Cys Ala Leu Cys Ala Gly Asp Asp 515 520 525 Gln Gly Leu Asp Lys Cys Val Pro Asn Ser Lys Glu Lys Tyr Tyr Gly 530 535 540 Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asp Val Gly Asp Val Ala 545 550 555 560 Phe Val Lys Asn Asp Thr Val Trp Glu Asn Thr Asn Gly Glu Ser Thr 565 570 575 Ala Asp Trp Ala Lys Asn Leu Asn Arg Glu Asp Phe Arg Leu Leu Cys 580 585 590 Leu Asp Gly Thr Arg Lys Pro Val Thr Glu Ala Gln Ser Cys His Leu 595 600 605 Ala Val Ala Pro Asn His Ala Val Val Ser Arg Ser Asp Arg Ala Ala 610 615 620 His Val Lys Gln Val Leu Leu His Gln Gln Ala Leu Phe Gly Lys Asn 625 630 635 640 Gly Lys Asn Cys Pro Asp Lys Phe Cys Leu Phe Lys Ser Glu Thr Lys 645 650 655 Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Lys Leu Gly Gly 660 665 670 Arg Pro Thr Tyr Glu Glu Tyr Leu Gly Thr Glu Tyr Val Thr Ala Ile 675 680 685 Ala Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys Ala 690 695 700 Phe Leu Thr Arg 705 <210> 3 <211> 695 <212> PRT <213> Equus caballus <400> 3 Leu Gly Leu Cys Leu Ala Ala Pro Arg Lys Ser Val Arg Trp Cys Thr 1 5 10 15 Ile Ser Pro Ala Glu Ala Ala Lys Cys Ala Lys Phe Gln Arg Asn Met 20 25 30 Lys Lys Val Arg Gly Pro Ser Val Ser Cys Ile Arg Lys Thr Ser Ser 35 40 45 Phe Glu Cys Ile Gln Ala Ile Ala Ala Asn Lys Ala Asp Ala Val Thr 50 55 60 Leu Asp Gly Gly Leu Val Tyr Glu Ala Gly Leu His Pro Tyr Lys Leu 65 70 75 80 Arg Pro Val Ala Ala Glu Val Tyr Gln Thr Arg Gly Lys Pro Gln Thr 85 90 95 Arg Tyr Tyr Ala Val Ala Val Val Lys Lys Gly Ser Gly Phe Gln Leu 100 105 110 Asn Gln Leu Gln Gly Val Lys Ser Cys His Thr Gly Leu Gly Arg Ser 115 120 125 Ala Gly Trp Asn Ile Pro Ile Gly Thr Leu Arg Pro Tyr Leu Asn Trp 130 135 140 Thr Gly Pro Pro Glu Pro Leu Gln Lys Ala Val Ala Asn Phe Phe Ser 145 150 155 160 Ala Ser Cys Val Pro Cys Ala Asp Gly Lys Gln Tyr Pro Asn Leu Cys 165 170 175 Arg Leu Cys Ala Gly Thr Glu Ala Asp Lys Cys Ala Cys Ser Ser Gln 180 185 190 Glu Pro Tyr Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Glu Asn Gly 195 200 205 Ala Gly Asp Val Ala Phe Val Lys Asp Ser Thr Val Phe Glu Asn Leu 210 215 220 Pro Asp Glu Ala Asp Arg Asp Lys Tyr Glu Leu Leu Cys Pro Asp Asn 225 230 235 240 Thr Arg Lys Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Arg Val 245 250 255 Pro Ser His Ala Val Val Ala Arg Ser Val Asp Gly Arg Glu Asp Leu 260 265 270 Ile Trp Arg Leu Leu His Arg Ala Gln Glu Glu Phe Gly Arg Asn Lys 275 280 285 Ser Ser Ala Phe Gln Leu Phe Lys Ser Thr Pro Glu Asn Lys Asp Leu 290 295 300 Leu Phe Lys Asp Ser Ala Leu Gly Phe Val Arg Ile Pro Ser Gln Ile 305 310 315 320 Asp Ser Gly Leu Tyr Leu Gly Ala Asn Tyr Leu Thr Ala Thr Gln Asn 325 330 335 Leu Arg Glu Thr Ala Ala Glu Val Ala Ala Arg Arg Glu Arg Val Val 340 345 350 Trp Cys Ala Val Gly Pro Glu Glu Glu Arg Lys Cys Lys Gln Trp Ser 355 360 365 Asp Val Ser Asn Arg Lys Val Ala Cys Ala Ser Ala Ser Thr Thr Glu 370 375 380 Glu Cys Ile Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Asn Leu 385 390 395 400 Asp Gly Gly Phe Ile Tyr Val Ala Gly Lys Cys Gly Leu Val Pro Val 405 410 415 Leu Ala Glu Asn Gln Lys Ser Gln Asn Ser Asn Ala Pro Asp Cys Val 420 425 430 His Arg Pro Pro Glu Gly Tyr Leu Ala Val Ala Val Val Arg Lys Ser 435 440 445 Asp Ala Asp Leu Thr Trp Asn Ser Leu Ser Gly Lys Lys Ser Cys His 450 455 460 Thr Gly Val Gly Arg Thr Ala Ala Trp Asn Ile Pro Met Gly Leu Leu 465 470 475 480 Phe Asn Gln Thr Gly Ser Cys Lys Phe Asp Lys Phe Phe Ser Gln Ser 485 490 495 Cys Ala Pro Gly Ala Asp Pro Gln Ser Ser Leu Cys Ala Leu Cys Val 500 505 510 Gly Asn Asn Glu Asn Glu Asn Lys Cys Met Pro Asn Ser Glu Glu Arg 515 520 525 Tyr Tyr Gly Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Lys Ala Gly 530 535 540 Asp Val Ala Phe Val Lys Asp Val Thr Val Leu Gln Asn Thr Asp Gly 545 550 555 560 Lys Asn Ser Glu Pro Trp Ala Lys Asp Leu Lys Gln Glu Asp Phe Glu 565 570 575 Leu Leu Cys Leu Asp Gly Thr Arg Lys Pro Val Ala Glu Ala Glu Ser 580 585 590 Cys His Leu Ala Arg Ala Pro Asn His Ala Val Val Ser Gln Ser Asp 595 600 605 Arg Ala Gln His Leu Lys Lys Val Leu Phe Leu Gln Gln Asp Gln Phe 610 615 620 Gly Gly Asn Gly Pro Asp Cys Pro Gly Lys Phe Cys Leu Phe Lys Ser 625 630 635 640 Glu Thr Lys Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Glu 645 650 655 Leu Gln Gly Lys Thr Thr Tyr Glu Gln Tyr Leu Gly Ser Glu Tyr Val 660 665 670 Thr Ser Ile Thr Asn Leu Arg Arg Cys Ser Ser Ser Pro Leu Leu Glu 675 680 685 Ala Cys Ala Phe Leu Arg Ala 690 695 <210> 4 <211> 708 <212> PRT <213> Capra hircus <400> 4 Met Lys Leu Phe Val Pro Ala Leu Leu Ser Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Ala Pro Arg Lys Asn Val Arg Trp Cys Ala Ile Ser Leu 20 25 30 Pro Glu Trp Ser Lys Cys Tyr Gln Trp Gln Arg Arg Met Arg Lys Leu 35 40 45 Gly Ala Pro Ser Ile Thr Cys Ile Arg Arg Thr Ser Ala Leu Glu Cys 50 55 60 Ile Arg Ala Ile Ala Gly Lys Asn Ala Asp Ala Val Thr Leu Asp Ser 65 70 75 80 Gly Met Val Phe Glu Ala Gly Leu Asp Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Ile Tyr Gly Thr Glu Lys Ser Pro Gln Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Ser Asn Phe Gln Leu Asp Gln Leu 115 120 125 Gln Gly Gln Lys Ser Cys His Met Gly Leu Gly Arg Ser Ala Gly Trp 130 135 140 Asn Ile Pro Val Gly Ile Leu Arg Pro Phe Leu Ser Trp Thr Glu Ser 145 150 155 160 Ala Glu Pro Leu Gln Gly Ala Val Ala Arg Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Cys Val Asp Gly Lys Ala Tyr Pro Asn Leu Cys Gln Leu Cys 180 185 190 Lys Gly Val Gly Glu Asn Lys Cys Ala Cys Ser Ser Gln Glu Pro Tyr 195 200 205 Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Gln Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Val Lys Glu Thr Thr Val Phe Glu Asn Leu Pro Glu Lys 225 230 235 240 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asn Asn Thr Arg Ala 245 250 255 Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Gln Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asp Gly Lys Glu Asn Leu Ile Trp Glu 275 280 285 Leu Leu Arg Lys Ala Gln Glu Lys Phe Gly Lys Asn Lys Ser Gln Ser 290 295 300 Phe Gln Leu Phe Gly Ser Pro Glu Gly Arg Arg Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Leu Gly Phe Val Arg Ile Pro Ser Lys Val Asp Ser Ala 325 330 335 Leu Tyr Leu Gly Ser Arg Tyr Leu Thr Ala Leu Lys Asn Leu Arg Glu 340 345 350 Thr Ala Glu Glu Leu Lys Ala Arg Cys Thr Arg Val Val Trp Cys Ala 355 360 365 Val Gly Pro Glu Glu Gln Ser Lys Cys Gln Gln Trp Ser Glu Gln Ser 370 375 380 Gly Gln Asn Val Thr Cys Ala Thr Ala Ser Thr Thr Asp Asp Cys Ile 385 390 395 400 Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Ser Leu Asp Gly Gly 405 410 415 Tyr Ile Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Met Ala Glu 420 425 430 Asn Arg Lys Ser Ser Lys Tyr Ser Ser Leu Asp Cys Val Leu Arg Pro 435 440 445 Thr Glu Gly Tyr Leu Ala Val Ala Val Val Lys Lys Ala Asn Glu Gly 450 455 460 Leu Thr Trp Asn Ser Leu Lys Gly Lys Lys Ser Cys His Thr Ala Val 465 470 475 480 Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Ile Ala Asn Gln 485 490 495 Thr Gly Ser Cys Ala Phe Asp Glu Phe Phe Ser Gln Ser Cys Ala Pro 500 505 510 Gly Ala Asp Pro Lys Ser Ser Leu Cys Ala Leu Cys Ala Gly Asp Asp 515 520 525 Gln Gly Leu Asp Lys Cys Val Pro Asn Ser Lys Glu Lys Tyr Tyr Gly 530 535 540 Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asp Val Gly Asp Val Ala 545 550 555 560 Phe Val Lys Asn Asp Thr Val Trp Glu Asn Thr Asn Gly Glu Ser Ser 565 570 575 Ala Asp Trp Ala Lys Asn Leu Asn Arg Glu Asp Phe Arg Leu Leu Cys 580 585 590 Leu Asp Gly Thr Thr Lys Pro Val Thr Glu Ala Gln Ser Cys Tyr Leu 595 600 605 Ala Val Ala Pro Asn His Ala Val Val Ser Arg Ser Asp Arg Ala Ala 610 615 620 His Val Glu Gln Val Leu Leu His Gln Gln Ala Leu Phe Gly Lys Asn 625 630 635 640 Gly Lys Asn Cys Pro Asp Gln Phe Cys Leu Phe Lys Ser Glu Thr Lys 645 650 655 Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Lys Leu Gly Gly 660 665 670 Arg Pro Thr Tyr Glu Lys Tyr Leu Gly Thr Glu Tyr Val Thr Ala Ile 675 680 685 Ala Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys Ala 690 695 700 Phe Leu Thr Arg 705 <210> 5 <211> 708 <212> PRT <213> Ovis aries <400> 5 Met Lys Leu Phe Val Pro Ala Leu Leu Ser Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Ala Pro Arg Lys Asn Val Arg Trp Cys Ala Ile Ser Pro 20 25 30 Pro Glu Gly Ser Lys Cys Tyr Gln Trp Gln Arg Arg Met Arg Lys Leu 35 40 45 Gly Ala Pro Ser Ile Thr Cys Val Arg Arg Thr Ser Ala Leu Glu Cys 50 55 60 Ile Arg Ala Ile Ala Gly Lys Lys Ala Asp Ala Val Thr Leu Asp Ser 65 70 75 80 Gly Met Val Phe Glu Ala Gly Leu Asp Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Ile Tyr Gly Thr Glu Lys Ser Pro Gln Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Ser Asn Phe Gln Leu Asp Gln Leu 115 120 125 Gln Gly Gln Lys Ser Cys His Thr Gly Leu Gly Arg Ser Ala Gly Trp 130 135 140 Asn Ile Pro Met Gly Ile Leu Arg Pro Phe Leu Ser Trp Thr Glu Ser 145 150 155 160 Ala Glu Pro Leu Gln Gly Ala Val Ala Arg Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Cys Val Asp Gly Lys Ala Tyr Pro Asn Leu Cys Gln Leu Cys 180 185 190 Lys Gly Val Gly Glu Asn Lys Cys Ala Cys Ser Ser Gln Glu Pro Tyr 195 200 205 Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Gln Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Val Lys Glu Thr Thr Val Phe Glu Asn Leu Pro Glu Lys 225 230 235 240 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asn Asn Thr Arg Ala 245 250 255 Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Gln Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asp Gly Lys Glu Asn Leu Ile Trp Glu 275 280 285 Leu Leu Arg Lys Ala Gln Glu Lys Phe Gly Lys Asn Lys Ser Pro Arg 290 295 300 Phe Gln Leu Phe Gly Ser Pro Gln Gly Gln Lys Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Leu Gly Phe Val Arg Ile Pro Ser Lys Val Asp Ser Ala 325 330 335 Leu Tyr Leu Gly Ser Arg Tyr Leu Thr Ala Leu Lys Asn Leu Arg Glu 340 345 350 Thr Ala Glu Glu Val Lys Ala Arg Cys Thr Arg Val Val Trp Cys Ala 355 360 365 Val Gly Pro Glu Glu His Ser Lys Cys Gln Gln Trp Ser Glu Gln Ser 370 375 380 Gly Gln Asn Val Thr Cys Ala Thr Ala Ser Thr Thr Asp Asp Cys Ile 385 390 395 400 Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Ser Leu Asp Gly Gly 405 410 415 Tyr Ile Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Met Ala Glu 420 425 430 Asn Arg Glu Ser Ser Lys Tyr Ser Ser Leu Asp Cys Val Leu Arg Pro 435 440 445 Thr Glu Gly Tyr Leu Ala Val Ala Val Val Lys Lys Ala Asn Glu Gly 450 455 460 Leu Thr Trp Asn Ser Leu Lys Gly Lys Lys Ser Cys His Thr Ala Val 465 470 475 480 Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Ile Ala Asn Gln 485 490 495 Thr Gly Ser Cys Ala Phe Asp Glu Phe Phe Ser Gln Ser Cys Ala Pro 500 505 510 Gly Ala Asp Pro Lys Ser Ser Leu Cys Ala Leu Cys Ala Gly Asp Asp 515 520 525 Gln Gly Leu Asn Lys Cys Val Pro Asn Ser Lys Glu Lys Tyr Tyr Gly 530 535 540 Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asp Val Gly Asp Val Ala 545 550 555 560 Phe Val Lys Asn Asp Thr Val Trp Glu Asn Thr Asn Gly Glu Ser Ser 565 570 575 Ala Asp Trp Ala Lys Asn Leu Asn Arg Glu Asp Phe Arg Leu Leu Cys 580 585 590 Leu Asp Gly Thr Thr Lys Pro Val Thr Glu Ala Gln Ser Cys Tyr Leu 595 600 605 Ala Val Ala Pro Asn His Ala Val Val Ser Arg Ser Asp Arg Ala Ala 610 615 620 His Val Glu Gln Val Leu Leu His Gln Gln Ala Leu Phe Gly Lys Asn 625 630 635 640 Gly Lys Asn Cys Pro Asp Gln Phe Cys Leu Phe Lys Ser Glu Thr Lys 645 650 655 Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Val Lys Leu Gly Gly 660 665 670 Arg Pro Thr Tyr Glu Lys Tyr Leu Gly Thr Glu Tyr Val Thr Ala Ile 675 680 685 Ala Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys Ala 690 695 700 Phe Leu Thr Arg 705 <210> 6 <211> 708 <212> PRT <213> Ovis aries <400> 6 Met Lys Leu Phe Val Pro Ala Leu Leu Ser Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Ala Pro Arg Lys Asn Val Arg Trp Cys Ala Ile Ser Pro 20 25 30 Pro Glu Gly Ser Lys Cys Tyr Gln Trp Gln Arg Arg Met Arg Lys Leu 35 40 45 Gly Ala Pro Ser Ile Thr Cys Val Arg Arg Thr Ser Ala Leu Glu Cys 50 55 60 Ile Arg Ala Ile Ala Gly Lys Lys Ala Asp Ala Val Thr Leu Asp Ser 65 70 75 80 Gly Met Val Phe Glu Ala Gly Leu Asp Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Ile Tyr Gly Thr Glu Lys Ser Pro Gln Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Ser Asn Phe Gln Leu Asp Gln Leu 115 120 125 Gln Gly Gln Lys Ser Cys His Met Gly Leu Gly Arg Ser Ala Gly Trp 130 135 140 Asn Ile Pro Met Gly Ile Leu Arg Pro Phe Leu Ser Trp Thr Glu Ser 145 150 155 160 Ala Glu Pro Leu Gln Gly Ala Val Ala Arg Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Cys Val Asp Gly Lys Ala Tyr Pro Asn Leu Cys Gln Leu Cys 180 185 190 Lys Gly Val Gly Glu Asn Lys Cys Ala Cys Ser Ser Gln Glu Pro Tyr 195 200 205 Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Gln Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Val Lys Glu Thr Thr Val Phe Glu Asn Leu Pro Glu Lys 225 230 235 240 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asn Asn Thr Arg Ala 245 250 255 Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Gln Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asp Gly Lys Glu Asn Leu Ile Trp Glu 275 280 285 Leu Leu Arg Lys Ala Gln Glu Lys Phe Gly Lys Asn Lys Ser Gln Arg 290 295 300 Phe Gln Leu Phe Gly Ser Pro Gln Gly Gln Lys Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Leu Gly Phe Val Arg Ile Pro Ser Lys Val Asp Ser Ala 325 330 335 Leu Tyr Leu Gly Ser Arg Tyr Leu Thr Ala Leu Lys Asn Leu Arg Glu 340 345 350 Thr Ala Glu Glu Val Lys Ala Arg Cys Thr Arg Val Val Trp Cys Ala 355 360 365 Val Gly Pro Glu Glu His Ser Lys Cys Gln Gln Trp Ser Glu Gln Ser 370 375 380 Gly Gln Asn Val Thr Cys Ala Met Ala Ser Thr Thr Asp Asp Cys Ile 385 390 395 400 Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Ser Leu Asp Gly Gly 405 410 415 Tyr Ile Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Met Ala Glu 420 425 430 Asn Arg Glu Ser Ser Lys Tyr Ser Ser Leu Asp Cys Val Leu Arg Pro 435 440 445 Thr Glu Gly Tyr Leu Ala Val Ala Val Val Lys Lys Ala Asn Glu Gly 450 455 460 Leu Thr Trp Asn Ser Leu Lys Gly Lys Lys Ser Cys His Thr Ala Val 465 470 475 480 Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Ile Ala Asn Gln 485 490 495 Thr Gly Ser Cys Ala Phe Asp Glu Phe Phe Ser Gln Ser Cys Ala Pro 500 505 510 Gly Ala Asp Pro Lys Ser Ser Leu Cys Ala Leu Cys Ala Gly Asp Asp 515 520 525 Gln Gly Leu Asn Lys Cys Val Pro Asn Ser Lys Glu Lys Tyr Tyr Gly 530 535 540 Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asp Val Gly Asp Val Ala 545 550 555 560 Phe Val Lys Asn Asp Thr Val Trp Glu Asn Thr Asn Gly Glu Ser Ser 565 570 575 Ala Asp Trp Ala Lys Asn Leu Asn Arg Glu Asp Phe Arg Leu Leu Cys 580 585 590 Leu Asp Gly Thr Thr Lys Pro Val Thr Glu Ala Gln Ser Cys Tyr Leu 595 600 605 Ala Val Ala Pro Asn His Ala Val Val Ser Arg Ser Asp Arg Ala Ala 610 615 620 His Val Glu Gln Val Leu Leu His Gln Gln Ala Leu Phe Gly Lys Asn 625 630 635 640 Gly Lys Asn Cys Pro Asp Gln Phe Cys Leu Phe Lys Ser Glu Thr Lys 645 650 655 Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Lys Leu Gly Gly 660 665 670 Arg Pro Thr Tyr Glu Lys Tyr Leu Gly Thr Glu Tyr Val Thr Ala Ile 675 680 685 Ala Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys Ala 690 695 700 Phe Leu Thr Arg 705 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> forward primer <400> 7 catgactttc ctggaattgg 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> reverse primer <400> 8 cctgcagttg aaccagctat 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> forward primer <400> 9 agcccatgtt gtagcaaacc 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> reverse primer <400> 10 ggaagacccc tcccagatag 20 <210> 11 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> forward primer <400> 11 cactgtgccc atctacg 17 <210> 12 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> reverse primer <400> 12 cttaatgtca cgcacgattt c 21 <110> LEE, Huisu <120> A composition containing lactoferrin derivative and manufacturing method thereof <130> P213190 <160> 12 <170> KoPatentIn 3.0 <210> 1 <211> 710 <212> PRT <213> Homo sapiens <400 > 1 Met Lys Leu Val Phe Leu Val Leu Leu Phe Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Gly Arg Arg Arg Ser Val Gln Trp Cys Ala Val Ser Gln 20 25 30 Pro Glu Ala Thr Lys Cys Phe Gln Trp Gln Arg Asn Met Arg Lys Val 35 40 45 Arg Gly Pro Pro Val Ser Cys Ile Lys Arg Asp Ser Pro Ile Gln Cys 50 55 60 Ile Gln Ala Ile Ala Glu Asn Arg Ala Asp Ala Val Thr Leu Asp Gly 65 70 75 80 Gly Phe Ile Tyr Glu Ala Gly Leu Ala Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Val Tyr Gly Thr Glu Arg Gln Pro Arg Thr His Tyr Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Gly Ser Phe Gln Leu Asn Glu Leu 115 120 125 Gln Gly Leu Lys Ser Cys His Thr Gly Leu Arg Arg Thr Ala Gly Trp 130 135 140 Asn Val Pro Ile Gly Thr Leu Arg Pro Phe Leu Asn Trp Thr Gly Pro 145 150 155 160 Pro Glu Pro Ile Glu Ala Ala Val Ala Arg Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Gly Ala Asp Lys Gly Gln Phe Pro Asn Leu Cys Arg Leu Cys 180 185 190 Ala Gly Thr Gly Glu Asn Lys Cys Ala Phe Ser Ser Gln Glu Pro Tyr 195 200 205 Phe Ser Tyr Ser Gly Ala Phe Lys Cys Leu Arg Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Ile Arg Glu Ser Thr Val Phe Glu Asp Leu Ser Asp Glu 225 230 235 240 Ala Glu Arg Asp Glu Tyr Glu Leu Leu Cys Pro Asp Asn Thr Arg Lys 245 250 255 Pro Val Asp Lys Phe Lys Asp Cys His Leu Ala Arg Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asn Gly Lys Glu Asp Ala Ile Trp Asn 275 280 285 Leu Leu Arg Gln Ala Gln Glu Lys Phe Gly Lys Asp Lys Ser Pro Lys 290 295 300 Phe Gln Leu Phe Gly Ser Pro Ser Gly Gln Lys Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Ile Gly Phe Ser Arg Val Pro Pro Arg Ile Asp Ser Gly 325 330 335 Leu Tyr Leu Gly Ser Gly Tyr Phe Thr Ala Ile Gln Asn Leu Arg Lys 340 345 350 Ser Glu Glu Glu Val Ala Ala Arg Arg Ala Arg Val Val Trp Cys Ala 355 360 365 Val Gly Glu Gln Glu Leu Arg Lys Cys Asn Gln Trp Ser Gly Leu Ser 370 375 380 Glu Gly Ser Val Thr Cys Ser Ser Ala Ser Thr Thr Glu Asp Cys Ile 385 390 395 400 Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Met Ser Leu Asp Gly Gly 405 410 415 Tyr Val Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Leu Ala Glu 420 425 430 Asn Tyr Lys Ser Gln Gln Ser Ser Asp Pro Asp Pro Asn Cys Val Asp 435 440 445 Arg Pro Val Glu Gly Tyr Leu Ala Val Ala Val Val Arg Arg Ser Asp 450 455 460 Thr Ser Leu Thr Trp Asn Ser Val Lys Gly Lys Lys Ser Cys His Thr 465 470 475 480 Ala Val Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Leu Phe 485 490 495 Asn Gln Thr Gly Ser Cys Lys Phe Asp Glu Tyr Phe Ser Gln Ser Cys 500 505 510 Ala Pro Gly Ser Asp Pro Arg Ser Asn Leu Cys Ala Leu Cys Ile Gly 515 520 525 Asp Glu Gln Gly Glu Asn Lys Cys Val Pro Asn Ser Asn Glu Arg Tyr 530 535 540 Tyr Gly Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asn Ala Gly Asp 545 550 555 560 Val Ala Phe Val Lys Asp Val Thr Val Leu Gln Asn Thr Asp Gly Asn 565 570 575 Asn Asn Glu Ala Trp Ala Lys Asp Leu Lys Leu Ala Asp Phe Ala Leu 580 585 590 Leu Cys Leu Asp Gly Lys Arg Lys Pro Val Thr Glu Ala Arg Ser Cys 595 600 605 His Leu Ala Met Ala Pro Asn His Ala Val Val Ser Arg Met Asp Lys 610 615 620 Val Glu Arg Leu Lys Gln Val Leu Leu His Gln Gln Ala Lys Phe Gly 625 630 635 640 Arg Asn Gly Ser Asp Cys Pro Asp Lys Phe Cys Leu Phe Gln Ser Glu 645 650 655 Thr Lys Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Arg Leu 660 665 670 His Gly Lys Thr Thr Tyr Glu Lys Tyr Leu Gly Pro Gln Tyr Val Ala 675 680 685 Gly Ile Thr Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala 690 695 700 Cys Glu Phe Leu Arg Lys 705 710 <210> 2 <211> 708 <212> PRT <213> Bos taurus <400> 2 Met Lys Leu Phe Val Pro Ala Leu Leu Ser Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Ala Pro Arg Lys Asn Val Arg Trp Cys Thr Ile Ser Gln 20 25 30 Pro Glu Trp Phe Lys Cys Arg Arg Trp Gln Trp Arg Met Lys Lys Leu 35 40 45 Gly Ala Pro Ser Ile Thr Cys Val Arg Arg Ala Phe Ala Leu Glu Cys 50 55 60 Ile Arg Ala Ile Ala Glu Lys Lys Ala Asp Ala Val Thr Leu Asp Gly 65 70 75 80 Gly Met Val Phe Glu Ala Gly Arg Asp Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Ile Tyr Gly Thr Lys Glu Ser Pro Gln Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Ser Asn Phe Gln Leu Asp Gln Leu 115 120 125 Gln Gly Arg Lys Ser Cys His Thr Gly Leu Gly Arg Ser Ala Gly Trp 130 135 140 Ile Ile Pro Met Gly Ile Leu Arg Pro Tyr Leu Ser Trp Thr Glu Ser 145 150 155 160 Leu Glu Pro Leu Gln Gly Ala Val Ala Lys Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Cys Ile Asp Arg Gln Ala Tyr Pro Asn Leu Cys Gln Leu Cys 180 185 190 Lys Gly Glu Gly Glu Asn Gln Cys Ala Cys Ser Ser Arg Glu Pro Tyr 195 200 205 Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Gln Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Val Lys Glu Thr Thr Val Phe Glu Asn Leu Pro Glu Lys 225 230 235 240 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asn Asn Ser Arg Ala 245 250 255 Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Gln Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asp Gly Lys Glu Asp Leu Ile Trp Lys 275 280 285 Leu Leu Ser Lys Ala Gln Glu Lys Phe Gly Lys Asn Lys Ser Arg Ser 290 295 300 Phe Gln Leu Phe Gly Ser Pro Pro Gly Gln Arg Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Leu Gly Phe Leu Arg Ile Pro Ser Lys Val Asp Ser Ala 325 330 335 Leu Tyr Leu Gly Ser Arg Tyr Leu Thr Thr Leu Lys Asn Leu Arg Glu 340 345 350 Thr Ala Glu Glu Val Lys Ala Arg Tyr Thr Arg Val Val Trp Cys Ala 355 360 365 Val Gly Pro Glu Glu Gln Lys Lys Cys Gln Gln Trp Ser Gln Gln Ser 370 375 380 Gly Gln Asn Val Thr Cys Ala Thr Ala Ser Thr Thr Thr Asp Asp Cys Ile 385 390 395 400 Val Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Asn Leu Asp Gly Gly 405 410 415 Tyr Ile Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Leu Ala Glu 420 425 430 Asn Arg Lys Ser Ser Lys His Ser Ser Leu Asp Cys Val Leu Arg Pro 435 440 445 Thr Glu Gly Tyr Leu Ala Val Ala Val Val Lys Lys Ala Asn Glu Gly 450 455 460 Leu Thr Trp Asn Ser Leu Lys Asp Lys Lys Lys Ser Cys His Thr Ala Val 465 470 475 480 Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Ile Val Asn Gln 485 490 495 Thr Gly Ser Cys Ala Phe Asp Glu Phe Phe Ser Gln Ser Cys Ala Pro 500 505 510 Gly Ala Asp Pro Lys Ser Arg Leu Cys Ala Leu Cys Ala Gly Asp Asp 515 520 525 Gln Gly Leu Asp Lys Cys Val Pro Asn Ser Lys Glu Lys Tyr Tyr Gly 530 535 540 Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asp Val Gly Asp Val Ala 545 550 555 560 Phe Val Lys Asn Asp Thr Val Trp Glu Asn Thr Asn Gly Glu Ser Thr 565 570 575 Ala Asp Trp Ala Lys Asn Leu Asn Arg Glu Asp Phe Arg Leu Leu Cys 580 585 590 Leu Asp Gly Thr Arg Lys Pro Val Thr Glu Ala Gln Ser Cys His Leu 595 600 605 Ala Val Ala Pro Asn His Ala Val Val Ser Arg Ser Asp Arg Ala Ala 610 615 620 His Val Lys Gln Val Leu Leu His Gln Gln Ala Leu Phe Gly Lys Asn 625 630 635 640 Gly Lys Asn Cys Pro Asp Lys Phe Cys Leu Phe Lys Ser Glu Thr Lys 645 650 655 Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Lys Leu Gly Gly 660 665 670 Arg Pro Thr Tyr Glu Glu Tyr Leu Gly Thr Glu Tyr Val Thr Ala Ile 675 680 685 Ala Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys Ala 690 695 700 Phe Leu Thr Arg 705 <210> 3 <211> 695 <212> PRT <213> Equus caballus <400> 3 Leu Gly Leu Cys Leu Ala Ala Pro Arg Lys Ser Val Arg Trp Cys Thr 1 5 10 15 Ile Ser Pro Ala Glu Ala Ala Lys Cys Ala Lys Phe Gln Arg Asn Met 20 25 30 Lys Lys Val Arg Gly Pro Ser Val Ser Cys Ile Arg Lys Thr Ser Ser 35 40 45 Phe Glu Cys Ile Gln Ala Ile Ala Ala Asn Lys Ala Asp Ala Val Thr 50 55 60 Leu Asp Gly Gly Leu Val Tyr Glu Ala Gly Leu His Pro Tyr Lys Leu 65 70 75 80 Arg Pro Val Ala Ala Glu Val Tyr Gln Thr Arg Gly Lys Pro Gln Thr 85 90 95 Arg Tyr Tyr Ala Val Ala Val Val Lys Lys Gly Ser Gly Phe Gln Leu 100 105 110 Asn Gln Leu Gln Gly Val Lys Ser Cys His Thr Gly Leu Gly Arg Ser 115 120 125 Ala Gly Trp Asn Ile Pro Ile Gly Thr Leu Arg Pro Tyr Leu Asn Trp 130 135 140 Thr Gly Pro Pro Glu Pro Leu Gln Lys Ala Val Ala Asn Phe Phe Ser 145 150 155 160 Ala Ser Cys Val Pro Cys Ala Asp Gly Lys Gln Tyr Pro Asn Leu Cys 165 170 175 Arg Leu Cys Ala Gly Thr Glu Ala Asp Lys Cys Ala Cys Ser Ser Gln 180 185 190 Glu Pro Tyr Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Glu Asn Gly 195 200 205 Ala Gly Asp Val Ala Phe Val Lys Asp Ser Thr Val Phe Glu Asn Leu 210 215 220 Pro Asp Glu Ala Asp Arg Asp Lys Tyr Glu Leu Leu Cys Pro Asp Asn 225 230 235 240 Thr Arg Lys Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Arg Val 245 250 255 Pro Ser His Ala Val Val Ala Arg Ser Val Asp Gly Arg Glu Asp Leu 260 265 270 Ile Trp Arg Leu Leu His Arg Ala Gln Glu Glu Phe Gly Arg Asn Lys 275 280 285 Ser Ser Ala Phe Gln Leu Phe Lys Ser Thr Pro Glu Asn Lys Asp Leu 290 295 300 Leu Phe Lys Asp Ser Ala Leu Gly Phe Val Arg Ile Pro Ser Gln Ile 305 310 315 320 Asp Ser Gly Leu Tyr Leu Gly Ala Asn Tyr Leu Thr Ala Thr Gln Asn 325 330 335 Leu Arg Glu Thr Ala Ala Glu Val Ala Ala Arg Arg Glu Arg Val Val 340 345 350 Trp Cys Ala Val Gly Pro Glu Glu Glu Arg Lys Cys Lys Gln Trp Ser 355 360 365 Asp Val Ser Asn Arg Lys Val Ala Cys Ala Ser Ala Ser Thr Thr Glu 370 375 380 Glu Cys Ile Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Asn Leu 385 390 395 400 Asp Gly Gly Phe Ile Tyr Val Ala Gly Lys Cys Gly Leu Val Pro Val 405 410 415 Leu Ala Glu Asn Gln Lys Ser Gln Asn Ser Asn Ala Pro Asp Cys Val 420 425 430 His Arg Pro Pro Glu Gly Tyr Leu Ala Val Ala Val Val Val Arg Lys Ser 435 440 445 Asp Ala Asp Leu Thr Trp Asn Ser Leu Ser Gly Lys Lys Ser Cys His 450 455 460 Thr Gly Val Gly Arg Thr Ala Ala Trp Asn Ile Pro Met Gly Leu Leu 465 470 475 480 Phe Asn Gln Thr Gly Ser Cys Lys Phe Asp Lys Phe Phe Ser Gln Ser 485 490 495 Cys Ala Pro Gly Ala Asp Pro Gln Ser Ser Leu Cys Ala Leu Cys Val 500 505 510 Gly Asn Asn Glu Asn Glu Asn Lys Cys Met Pro Asn Ser Glu Glu Arg 515 520 525 Tyr Tyr Gly Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Lys Ala Gly 530 535 540 Asp Val Ala Phe Val Lys Asp Val Thr Val Leu Gln Asn Thr Asp Gly 545 550 555 560 Lys Asn Ser Glu Pro Trp Ala Lys Asp Leu Lys Gln Glu Asp Phe Glu 565 570 575 Leu Leu Cys Leu Asp Gly Thr Arg Lys Pro Val Ala Glu Ala Glu Ser 580 585 590 Cys His Leu Ala Arg Ala Pro Asn His Ala Val Val Ser Gln Ser Asp 595 600 605 Arg Ala Gln His Leu Lys Lys Val Leu Phe Leu Gln Gln Asp Gln Phe 610 615 620 Gly Gly Asn Gly Pro Asp Cys Pro Gly Lys Phe Cys Leu Phe Lys Ser 625 630 635 640 Glu Thr Lys Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Glu 645 650 655 Leu Gln Gly Lys Thr Thr Tyr Glu Gln Tyr Leu Gly Ser Glu Tyr Val 660 665 670 Thr Ser Ile Thr Asn Leu Arg Arg Cys Ser Ser Ser Pro Leu Leu Glu 675 680 685 Ala Cys Ala Phe Leu Arg Ala 690 695 <210> 4 <211> 708 <212> PRT <213> Capra hircus < 400>4 Met Lys Leu Phe Val Pro Ala Leu Leu Ser Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Ala Pro Arg Lys Asn Val Arg Trp Cys Ala Ile Ser Leu 20 25 30 Pro Glu Trp Ser Lys Cys Tyr Gln Trp Gln Arg Arg Met Arg Lys Leu 35 40 45 Gly Ala Pro Ser Ile Thr Cys Ile Arg Arg Thr Ser Ala Leu Glu Cys 50 55 60 Ile Arg Ala Ile Ala Gly Lys Asn Ala Asp Ala Val Thr Leu Asp Ser 65 70 75 80 Gly Met Val Phe Glu Ala Gly Leu Asp Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Ile Tyr Gly Thr Glu Lys Ser Pro Gln Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Ser Asn Phe Gln Leu Asp Gln Leu 115 120 125 Gln Gly Gln Lys Ser Cys His Met Gly Leu Gly Arg Ser Ala Gly Trp 130 135 140 Asn Ile Pro Val Gly Ile Leu Arg Pro Phe Leu Ser Trp Thr Glu Ser 145 150 155 160 Ala Glu Pro Leu Gln Gly Ala Val Ala Arg Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Cys Val Asp Gly Lys Ala Tyr Pro Asn Leu Cys Gln Leu Cys 180 185 190 Lys Gly Val Gly Glu Asn Lys Cys Ala Cys Ser Ser Ser Gln Glu Pro Tyr 195 200 205 Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Gln Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Val Lys Glu Thr Thr Val Phe Glu Asn Leu Pro Glu Lys 225 230 235 240 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asn Asn Thr Arg Ala 245 250 255 Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Gln Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asp Gly Lys Glu Asn Leu Ile Trp Glu 275 280 285 Leu Leu Arg Lys Ala Gln Glu Lys Phe Gly Lys Asn Lys Ser Gln Ser 290 295 300 Phe Gln Leu Phe Gly Ser Pro Glu Gly Arg Arg Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Leu Gly Phe Val Arg Ile Pro Ser Lys Val Asp Ser Ala 325 330 335 Leu Tyr Leu Gly Ser Arg Tyr Leu Thr Ala Leu Lys Asn Leu Arg Glu 340 345 350 Thr Ala Glu Glu Leu Lys Ala Arg Cys Thr Arg Val Val Trp Cys Ala 355 360 365 Val Gly Pro Glu Glu Gln Ser Lys Cys Gln Gln Trp Ser Glu Gln Ser 370 375 380 Gly Gln Asn Val Thr Cys Ala Thr Ala Ser Thr Thr Asp Asp Cys Ile 385 390 395 400 Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Ser Leu Asp Gly Gly 405 410 415 Tyr Ile Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Met Ala Glu 420 425 430 Asn Arg Lys Ser Ser Lys Tyr Ser Ser Leu Asp Cys Val Leu Arg Pro 435 440 445 Thr Glu Gly Tyr Leu Ala Val Ala Val Val Lys Lys Ala Asn Glu Gly 450 455 460 Leu Thr Trp Asn Ser Leu Lys Gly Lys Lys Ser Cys His Thr Ala Val 465 470 475 480 Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Ile Ala Asn Gln 485 490 495 Thr Gly Ser Cys Ala Phe Asp Glu Phe Phe Ser Gln Ser Cys Ala Pro 500 505 510 Gly Ala Asp Pro Lys Ser Ser Leu Cys Ala Leu Cys Ala Gly Asp Asp 515 520 525 Gln Gly Leu Asp Lys Cys Val Pro Asn Ser Lys Glu Lys Tyr Tyr Gly 530 535 540 Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asp Val Gly Asp Val Ala 545 550 555 560 Phe Val Lys Asn Asp Thr Val Trp Glu Asn Thr Asn Gly Glu Ser Ser 565 570 575 Ala Asp Trp Ala Lys Asn Leu Asn Arg Glu Asp Phe Arg Leu Leu Cys 580 585 590 Leu Asp Gly Thr Thr Lys Pro Val Thr Glu Ala Gln Ser Cys Tyr Leu 595 600 605 Ala Val Ala Pro Asn His Ala Val Val Ser Arg Ser Asp Arg Ala Ala 610 615 620 His Val Glu Gln Val Leu Leu His Gln Gln Ala Leu Phe Gly Lys Asn 625 630 635 640 Gly Lys Asn Cys Pro Asp Gln Phe Cys Leu Phe Lys Ser Glu Thr Lys 645 650 655 Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Lys Leu Gly Gly 660 665 670 Arg Pro Thr Tyr Glu Lys Tyr Leu Gly Thr Glu Tyr Val Thr Ala Ile 675 680 685 Ala Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys Ala 690 695 700 Phe Leu Thr Arg 705 <210> 5 <211> 708 <212> PRT <213> Ovis aries <400> 5 Met Lys Leu Phe Val Pro Ala Leu Leu Ser Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Ala Pro Arg Lys Asn Val Arg Trp Cys Ala Ile Ser Pro 20 25 30 Pro Glu Gly Ser Lys Cys Tyr Gln Trp Gln Arg Arg Met Arg Lys Leu 35 40 45 Gly Ala Pro Ser Ile Thr Cys Val Arg Arg Thr Ser Ala Leu Glu Cys 50 55 60 Ile Arg Ala Ile Ala Gly Lys Lys Ala Asp Ala Val Thr Leu Asp Ser 65 70 75 80 Gly Met Val Phe Glu Ala Gly Leu Asp Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Ile Tyr Gly Thr Glu Lys Ser Pro Gln Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Ser Asn Phe Gln Leu Asp Gln Leu 115 120 125 Gln Gly Gln Lys Ser Cys His Thr Gly Leu Gly Arg Ser Ala Gly Trp 130 135 140 Asn Ile Pro Met Gly Ile Leu Arg Pro Phe Leu Ser Trp Thr Glu Ser 145 150 155 160 Ala Glu Pro Leu Gln Gly Ala Val Ala Arg Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Cys Val Asp Gly Lys Ala Tyr Pro Asn Leu Cys Gln Leu Cys 180 185 190 Lys Gly Val Gly Glu Asn Lys Cys Ala Cys Ser Ser Gln Glu Pro Tyr 195 200 205 Phe Gly Tyr Ser Gly Ala Phe Lys Cys Leu Gln Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Val Lys Glu Thr Thr Val Phe Glu Asn Leu Pro Glu Lys 225 230 235 240 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asn Asn Thr Arg Ala 245 250 255 Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Gln Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asp Gly Lys Glu Asn Leu Ile Trp Glu 275 280 285 Leu Leu Arg Lys Ala Gln Glu Lys Phe Gly Lys Asn Lys Ser Pro Arg 290 295 300 Phe Gln Leu Phe Gly Ser Pro Gln Gly Gln Lys Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Leu Gly Phe Val Arg Ile Pro Ser Lys Val Asp Ser Ala 325 330 335 Leu Tyr Leu Gly Ser Arg Tyr Leu Thr Ala Leu Lys Asn Leu Arg Glu 340 345 350 Thr Ala Glu Glu Val Lys Ala Arg Cys Thr Arg Val Val Trp Cys Ala 355 360 365 Val Gly Pro Glu Glu His Ser Lys Cys Gln Gln Trp Ser Glu Gln Ser 370 375 380 Gly Gln Asn Val Thr Cys Ala Thr Ala Ser Thr Thr Asp Asp Cys Ile 385 390 395 400 Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Ser Leu Asp Gly Gly 405 410 415 Tyr Ile Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Met Ala Glu 420 425 430 Asn Arg Glu Ser Ser Lys Tyr Ser Ser Leu Asp Cys Val Leu Arg Pro 435 440 445 Thr Glu Gly Tyr Leu Ala Val Ala Val Val Lys Lys Ala Asn Glu Gly 450 455 460 Leu Thr Trp Asn Ser Leu Lys Gly Lys Lys Ser Cys His Thr Ala Val 465 470 475 480 Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Ile Ala Asn Gln 485 490 495 Thr Gly Ser Cys Ala Phe Asp Glu Phe Phe Ser Gln Ser Cys Ala Pro 500 505 510 Gly Ala Asp Pro Lys Ser Ser Leu Cys Ala Leu Cys Ala Gly Asp Asp 515 520 525 Gln Gly Leu Asn Lys Cys Val Pro Asn Ser Lys Glu Lys Tyr Tyr Gly 530 535 540 Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asp Val Gly Asp Val Ala 545 550 555 560 Phe Val Lys Asn Asp Thr Val Trp Glu Asn Thr Asn Gly Glu Ser Ser 565 570 575 Ala Asp Trp Ala Lys Asn Leu Asn Arg Glu Asp Phe Arg Leu Leu Cys 580 585 590 Leu Asp Gly Thr Thr Lys Pro Val Thr Glu Ala Gln Ser Cys Tyr Leu 595 600 605 Ala Val Ala Pro Asn His Ala Val Val Ser Arg Ser Asp Arg Ala Ala 610 615 620 His Val Glu Gln Val Leu Leu His Gln Gln Ala Leu Phe Gly Lys Asn 625 630 635 640 Gly Lys Asn Cys Pro Asp Gln Phe Cys Leu Phe Lys Ser Glu Thr Lys 645 650 655 Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Val Lys Leu Gly Gly 660 665 670 Arg Pro Thr Tyr Glu Lys Tyr Leu Gly Thr Glu Tyr Val Thr Ala Ile 675 680 685 Ala Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys Ala 690 695 700 Phe Leu Thr Arg 705 <210> 6 <211> 708 <212> PRT <213> Ovis aries <400> 6 Met Lys Leu Phe Val Pro Ala Leu Leu Ser Leu Gly Ala Leu Gly Leu 1 5 10 15 Cys Leu Ala Ala Pro Arg Lys Asn Val Arg Trp Cys Ala Ile Ser Pro 20 25 30 Pro Glu Gly Ser Lys Cys Tyr Gln Trp Gln Arg Arg Met Arg Lys Leu 35 40 45 Gly Ala Pro Ser Ile Thr Cys Val Arg Arg Thr Ser Ala Leu Glu Cys 50 55 60 Ile Arg Ala Ile Ala Gly Lys Lys Ala Asp Ala Val Thr Leu Asp Ser 65 70 75 80 Gly Met Val Phe Glu Ala Gly Leu Asp Pro Tyr Lys Leu Arg Pro Val 85 90 95 Ala Ala Glu Ile Tyr Gly Thr Glu Lys Ser Pro Gln Thr His Tyr Tyr 100 105 110 Ala Val Ala Val Val Lys Lys Gly Ser Asn Phe Gln Leu Asp Gln Leu 115 120 125 Gln Gly Gln Lys Ser Cys His Met Gly Leu Gly Arg Ser Ala Gly Trp 130 135 140 Asn Ile Pro Met Gly Ile Leu Arg Pro Phe Leu Ser Trp Thr Glu Ser 145 150 155 160 Ala Glu Pro Leu Gln Gly Ala Val Ala Arg Phe Phe Ser Ala Ser Cys 165 170 175 Val Pro Cys Val Asp Gly Lys Ala Tyr Pro Asn Leu Cys Gln Leu Cys 180 185 190 Lys Gly Val Gly Glu Asn Lys Cys Ala Cys Ser Ser Gln Glu Tyr Pro Tyr 195 200 205 Phe Gly Ser Gly Ala Phe Lys Cys Leu Gln Asp Gly Ala Gly Asp 210 215 220 Val Ala Phe Val Lys Glu Thr Thr Val Phe Glu Asn Leu Pro Glu Lys 225 230 235 240 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asn Asn Thr Arg Ala 245 250 255 Pro Val Asp Ala Phe Lys Glu Cys His Leu Ala Gln Val Pro Ser His 260 265 270 Ala Val Val Ala Arg Ser Val Asp Gly Lys Glu Asn Leu Ile Trp Glu 275 280 285 Leu Leu Arg Lys Ala Gln Glu Lys Phe Gly Lys Asn Lys Ser Gln Arg 290 295 300 Phe Gln Leu Phe Gly Ser Pro Gln Gly Gln Lys Asp Leu Leu Phe Lys 305 310 315 320 Asp Ser Ala Leu Gly Phe Val Arg Ile Pro Ser Lys Val Asp Ser Ala 325 330 335 Leu Tyr Leu Gly Ser Arg Tyr Leu Thr Ala Leu Lys Asn Leu Arg Glu 340 345 350 Thr Ala Glu Glu Val Lys Ala Arg Cys Thr Arg Val Val Trp Cys Ala 355 360 365 Val Gly Pro Glu Glu His Ser Lys Cys Gln Gln Trp Ser Glu Gln Ser 370 375 380 Gly Gln Asn Val Thr Cys Ala Met Ala Ser Thr Thr Asp Asp Cys Ile 385 390 395 400 Ala Leu Val Leu Lys Gly Glu Ala Asp Ala Leu Ser Leu Asp Gly Gly 405 410 415 Tyr Ile Tyr Thr Ala Gly Lys Cys Gly Leu Val Pro Val Met Ala Glu 420 425 430 Asn Arg Glu Ser Ser Lys Tyr Ser Ser Leu Asp Cys Val Leu Arg Pro 435 440 445 Thr Glu Gly Tyr Leu Ala Val Ala Val Val Lys Lys Ala Asn Glu Gly 450 455 460 Leu Thr Trp Asn Ser Leu Lys Gly Lys Lys Ser Cys His Thr Ala Val 465 470 475 480 Asp Arg Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Ile Ala Asn Gln 485 490 495 Thr Gly Ser Cys Ala Phe Asp Glu Phe Phe Ser Gln Ser Cys Ala Pro 500 505 510 Gly Ala Asp Pro Lys Ser Ser Leu Cys Ala Leu Cys Ala Gly Asp Asp 515 520 525 Gln Gly Leu Asn Lys Cys Val Pro Asn Ser Lys Glu Lys Tyr Tyr Gly 530 535 540 Tyr Thr Gly Ala Phe Arg Cys Leu Ala Glu Asp Val Gly Asp Val Ala 545 550 555 560 Phe Val Lys Asn Asp Thr Val Trp Glu Asn Thr Asn Gly Glu Ser Ser 565 570 575 Ala Asp Trp Ala Lys Asn Leu Asn Arg Glu Asp Phe Arg Leu Leu Cys 580 585 590 Leu Asp Gly Thr Thr Lys Pro Val Thr Glu Ala Gln Ser Cys Tyr Leu 595 600 605 Ala Val Ala Pro Asn His Ala Val Val Ser Arg Ser Asp Arg Ala Ala 610 615 620 His Val Glu Gln Val Leu Leu His Gln Gln Ala Leu Phe Gly Lys Asn 625 630 635 640 Gly Lys Asn Cys Pro Asp Gln Phe Cys Leu Phe Lys Ser Glu Thr Lys 645 650 655 Asn Leu Leu Phe Asn Asp Asn Thr Glu Cys Leu Ala Lys Leu Gly Gly 660 665 670 Arg Pro Thr Tyr Glu Lys Tyr Leu Gly Thr Glu Tyr Val Thr Ala Ile 675 680 685 Ala Asn Leu Lys Lys Cys Ser Thr Ser Pro Leu Leu Glu Ala Cys Ala 690 695 700 Phe Leu Thr Arg 705 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> forward primer <400> 7 catgactttc ctggaattgg 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223 > reverse primer <400> 8 cctgcagttg aaccagctat 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> forward primer <400> 9 agcccatgtt gtagcaaacc 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> reverse primer <400> 10 ggaagacccc tcccagatag 20 <210> 11 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> forward primer < 400> 11 cactgtgccc atctacg 17 <210> 12 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> reverse primer<400> 12 cttaatgtca cgcacgattt c 21
Claims (9)
A pharmaceutical composition for preventing or treating inflammatory diseases, comprising a lactoferrin derivative as an active ingredient.
상기 락토페린 유도체는 화학식 1 및 2에서 선택된 어느 하나 이상의 단위를 포함하는 축합중합체인, 염증성 질환의 예방 또는 치료용 약학적 조성물:
[화학식 1]
[화학식 2]
상기 화학식 1에서 M+는 금속 양이온이고,
상기 화학식 1 및 2에서 LF는 락토페린을 포함하는 것이다.
According to claim 1,
The lactoferrin derivative is a condensation polymer comprising at least one unit selected from Formulas 1 and 2, a pharmaceutical composition for preventing or treating inflammatory diseases:
[Formula 1]
[Formula 2]
In Formula 1, M + is a metal cation,
In Formulas 1 and 2, LF includes lactoferrin.
상기 축합중합체는 화학식 3으로 표시될 수 있는 단위를 더 포함하는 것인, 염증성 질환의 예방 또는 치료용 약학적 조성물:
[화학식 3]
According to claim 2,
The condensation polymer further comprises a unit that may be represented by Formula 3, a pharmaceutical composition for preventing or treating inflammatory diseases:
[Formula 3]
A cosmetic composition for skin improvement comprising a lactoferrin derivative as an active ingredient.
상기 락토페린 유도체는 화학식 1 및 2에서 선택된 어느 하나 이상의 단위를 포함하는 축합중합체인, 피부 개선용 화장료 조성물:
[화학식 1]
[화학식 2]
상기 화학식 1에서 M+은 금속 양이온이고,
상기 화학식 1 및 2에서 LF는 락토페린을 포함하는 것이다.
According to claim 4,
The lactoferrin derivative is a condensation polymer comprising at least one unit selected from Formulas 1 and 2, a cosmetic composition for improving skin:
[Formula 1]
[Formula 2]
In Formula 1, M + is a metal cation,
In Formulas 1 and 2, LF includes lactoferrin.
상기 축합중합체는 화학식 3으로 표시될 수 있는 단위를 더 포함하는 것인, 피부 개선용 화장료 조성물:
[화학식 3]
According to claim 5,
The condensation polymer further comprises a unit represented by Formula 3, a cosmetic composition for improving skin:
[Formula 3]
글리세린, 부틸렌글리콜, 프로필렌글리콜, 폴리옥시에틸렌 경화피마자유, 에탄올, 트리에탄올아민, 밀납, 폴리솔베이트 60, 솔비탄 세스퀴올레이트, 유동 파라핀, 소르비탄 스테아레이트, 친유형 모노스테아린산 글리세린, 스테아린산, 글리세릴스테아레이트/피이지-400 스테아레이트, 카르복시폴리머, 시토스테롤, 폴리에틸렌 글리콜, 세라마이드, 스테아르산, 콜레스테롤, 디세틸포스페이트, 마카다미아 오일, 카르복시비닐폴리머, 신탄검, 잔탄검, 소이빈포스포리피드, 하이드록시에틸셀룰로오즈 및 히아루론산염으로 이루어진 군에서 선택된 4 이상을 더 포함하는 것인, 피부 개선용 화장료 조성물.
According to claim 4,
Glycerin, butylene glycol, propylene glycol, polyoxyethylene hydrogenated castor oil, ethanol, triethanolamine, beeswax, polysorbate 60, sorbitan sesquioleate, liquid paraffin, sorbitan stearate, lipophilic monostearate glycerin, stearic acid, Glyceryl Stearate/PEG-400 Stearate, Carboxypolymer, Sitosterol, Polyethylene Glycol, Ceramide, Stearic Acid, Cholesterol, Dicetyl Phosphate, Macadamia Oil, Carboxyvinyl Polymer, Syntan Gum, Xanthan Gum, Soybean Phospholipid, A cosmetic composition for skin improvement that further comprises 4 or more selected from the group consisting of hydroxyethyl cellulose and hyaluronic acid salts.
상기 락토페린 유도체 100 중량부에 대하여, 상기 글리세린은 400 내지 800 중량부, 상기 부틸렌글리콜은 200 내지 600 중량부, 상기 프로필렌글리콜은 100 내지 300 중량부 및 상기 트리에탄올아민은 5 내지 30 중량부인 것인, 피부 개선용 화장료 조성물.
According to claim 7,
Based on 100 parts by weight of the lactoferrin derivative, the glycerin is 400 to 800 parts by weight, the butylene glycol is 200 to 600 parts by weight, the propylene glycol is 100 to 300 parts by weight, and the triethanolamine is 5 to 30 parts by weight , A cosmetic composition for skin improvement.
락토페린을 첨가하는 단계; 및
정제 용매를 첨가하여 정제하는 단계;를 포함하고,
상기 시료는 산화제 또는 커플링제인, 락토페린 유도체를 제조하는 방법.
Adding a sample to hyaluronic acid;
adding lactoferrin; and
Purifying by adding a purification solvent; Including,
Wherein the sample is an oxidizing agent or a coupling agent, a method for producing a lactoferrin derivative.
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| Application Number | Priority Date | Filing Date | Title |
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| KR1020210152679A KR20230067034A (en) | 2021-11-09 | 2021-11-09 | Method for producing lactoferrin derivative having functions such as antioxidant, whitening, anti-inflammatory and skin protection, and skin treatment ointment and cosmetic composition comprising the same |
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| Application Number | Priority Date | Filing Date | Title |
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| KR1020210152679A KR20230067034A (en) | 2021-11-09 | 2021-11-09 | Method for producing lactoferrin derivative having functions such as antioxidant, whitening, anti-inflammatory and skin protection, and skin treatment ointment and cosmetic composition comprising the same |
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2021
- 2021-11-09 KR KR1020210152679A patent/KR20230067034A/en not_active Application Discontinuation
Non-Patent Citations (2)
| Title |
|---|
| Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization, L. Tang, 2010. |
| The therapeutic potential of lactoferrin, Eugene D Weinberg, 2013. |
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