TW201313204A - Dental implant with hydrophilic moisturized coating and method for manufacturing the same - Google Patents

Dental implant with hydrophilic moisturized coating and method for manufacturing the same Download PDF

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TW201313204A
TW201313204A TW101132790A TW101132790A TW201313204A TW 201313204 A TW201313204 A TW 201313204A TW 101132790 A TW101132790 A TW 101132790A TW 101132790 A TW101132790 A TW 101132790A TW 201313204 A TW201313204 A TW 201313204A
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dental implant
implant
hydrophilic
moisturizing film
coated
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TWI563985B (en
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Yong-Il Chung
ju-dong Song
Eun-Jung Kang
Tae-Gwan Eom
Kyoo-Ok Choi
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Osstem Implant Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
    • A61C8/0013Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy with a surface layer, coating
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/04Metals or alloys
    • A61L27/06Titanium or titanium alloys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/34Macromolecular materials

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dentistry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Ceramic Engineering (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The present invention relates to a dental implant on which a hydrophilic water-retaining layer is coated, and a manufacturing method thereof. More specifically, the dental implant in which a hydrophilic water-retaining layer is coated on the surface thereof, according to the invention, improves the blood protein adhesion ability and hemocompatibility of a dental implant, thereby enabling effective osseointegration. Therefore, the invention can be used for the manufacture of an implant having improved osseointegration while imparting hydrophilic surface properties by preventing the hydrophobization of the surface of the implant.

Description

具親水性保濕膜塗覆的牙科用植體及其製造方法 Dental implant coated with hydrophilic moisturizing film and manufacturing method thereof

本發明涉及表面塗覆有親水性保濕膜的牙科用植體及其製造方法。 The present invention relates to a dental implant having a surface coated with a hydrophilic moisturizing film and a method of producing the same.

牙科用植體(以下簡稱植體)是能夠用來永久代替缺損的牙齒的人工牙齒,要求在功能上能夠代替執行牙齒的功能。不僅如此,要製造成在咀嚼中能夠適當分散施加到牙齒的負荷而能夠長期使用,在美觀上也要求製作精細從而具有與實際的牙齒沒有太大的差別的形態和色澤。 Dental implants (hereinafter referred to as implants) are artificial teeth that can be used to permanently replace a defective tooth, and are required to be functionally capable of performing the function of the tooth. In addition, it is possible to manufacture a load that can be appropriately dispersed and applied to the teeth during chewing, and can be used for a long period of time, and it is also required to be finely made in appearance so as to have a form and a color which are not much different from the actual teeth.

植體移植到口腔內的生體組織,即齒槽骨內並被固定,在植入體內後隨著時間的流逝,由於體內組織液和體液或與體組織的接觸和摩擦,金屬植體的金屬離子溶出,因此腐蝕植體。此外,從金屬植體溶出的金屬離子損傷體內的巨噬細胞或侵入到體細胞中,成為產生炎症細胞和巨細胞的原因,因此植體的生體融合性要優秀。 The implant is transplanted into the living tissue in the oral cavity, that is, in the alveolar bone and fixed. After the implantation in the body, the metal of the metal implant is contacted and rubbed by the body fluid and the body fluid or the body tissue. The ions are dissolved, thus corroding the implant. In addition, metal ions eluted from metal implants damage macrophages in the body or invade into somatic cells, which cause inflammatory cells and giant cells. Therefore, the implant has excellent biocompatibility.

這種植體材料被嘗試使用多種金屬及合金而開發,但是使用對人體生體組織具有高度的生體親和性、高機械強度及生體惰性的鈦金屬及其合金為其目前發展趨勢。 This implant material has been developed using a variety of metals and alloys, but titanium metal and its alloys which have high biocompatibility, high mechanical strength and bio-inertity to human body tissues are currently in development.

另一方面,使用增加植體的表面粗糙度,增加與生體組織接觸的變面積的方法,從而使植體在生體內穩定的骨結合。增加植體表面積的代表性的處理方法-粒子噴射後酸處理法(Sandblasting with large grit and Acid treatment,以下簡稱SA法)是在植體表面噴射(blasting)氧化鋁(Al2O3)粒子,產生坑(crater)和微粒(micro-pit)後進行強酸(H2SO4/HCl)處理的方法,相比以往的吸收性噴射媒介法(resorbable blasting media,RBM)增加了40%以上的表面積,從而通過粒子噴射後酸處理方法製造的植體將種植手術後的平均治癒時間從12週縮短到6-8週。 On the other hand, a method of increasing the surface roughness of the implant and increasing the variable area in contact with the living tissue is used, thereby making the implant stable in bone binding in the living body. A typical treatment method for increasing the surface area of the implant - Sandblasting with large grit and acid treatment (SA method) is to blast the alumina (Al 2 O 3 ) particles on the surface of the implant to produce pits ( The method of treatment with strong acid (H2SO4/HCl) after crater and micro-pit increases the surface area by more than 40% compared with the conventional resorbable blasting media (RBM), so that after particle spraying The implants produced by the acid treatment method reduced the average healing time after implantation from 12 weeks to 6-8 weeks.

但是,通過SA法表面處理的親水性鈦表面,其具有在空氣中由於碳污染源的非可逆吸收而迅速疏水化的缺點。疏水化的表面妨礙骨細胞向植體表面滲入,從種植初期就開始減少骨和植體之間的接觸率,可能會成為初期種植手術失敗的潛在的理由。 However, the surface of the hydrophilic titanium surface-treated by the SA method has a drawback of being rapidly hydrophobized due to irreversible absorption of a carbon contamination source in the air. The hydrophobized surface prevents the infiltration of bone cells into the surface of the implant, and reducing the contact rate between the bone and the implant from the early stage of planting may be a potential reason for the failure of the initial implant surgery.

從而提出了防止SA方法製造的鈦植體表面在大氣中疏水化維持親水性的對策,其中代表性的有將鈦植體放到填充有水或惰性氣體的容器中包裝,從而阻斷與空氣的接觸。 Therefore, countermeasures against the hydrophobicity of the titanium implant surface manufactured by the SA method in the atmosphere to maintain hydrophilicity are proposed, and a representative example is that the titanium implant is packaged in a container filled with water or an inert gas, thereby blocking the air. s contact.

如上所述的包裝方法在維持鈦植體表面親水性的側面相當有效,但是近來的植體開發方向來看時可能伴隨使用上的限制。即,近來植體開發的一個大主流是在植體表面塗覆能夠促進骨結合(osseointegration)的化學物質、肽或蛋白質等,從而縮短種植手術期間,塗覆這些物質的植體用水包裹時,會對塗覆層產生什麼樣的影響並未得到驗證,如果產生有害影響,就需要能夠解決該問題的其他包裝媒介。 The packaging method as described above is quite effective in maintaining the hydrophilicity of the surface of the titanium implant, but the recent development of the implant may be accompanied by limitations in use. That is, a major mainstream of recent implant development is to coat the surface of the implant with chemicals, peptides or proteins that promote osseointegration, thereby shortening the time during the implantation operation, when the implants coated with these substances are wrapped with water. What effect on the coating is not verified, and if it has a detrimental effect, other packaging media that can solve the problem are needed.

從而,從與以往造成惰性環境的包裝方法全然不同的理念出發,需要開發一種能夠防止植體表面的疏水化,從而維持親水性表面特性,提高血液親和性,提高種植初期骨結合性能的新型植體。 Therefore, it is necessary to develop a new type of plant that can prevent the hydrophobization of the surface of the implant, thereby maintaining the hydrophilic surface characteristics, improving the blood affinity, and improving the osseointegration performance at the initial stage of planting, from the concept that the packaging method of the inert environment is completely different. body.

本發明的目的在於提供一種能夠維持利用SA法在鈦植體表面賦予的親水性,以形成親水性保濕膜的牙科用植體及其製造方法。 An object of the present invention is to provide a dental implant capable of maintaining hydrophilicity imparted to the surface of a titanium implant by the SA method to form a hydrophilic moisturizing film, and a method for producing the same.

本發明提供包括鈦或鈦合金材質之具有粗糙表面的牙科用植體;以及在所述牙科用植體形成保持所述表面的親水性且在常溫維持濕潤狀態的親水性保濕膜的牙科用植體。 The present invention provides a dental implant having a rough surface comprising a titanium or titanium alloy material; and a dental implant in the dental implant that forms a hydrophilic moisturizing film that maintains the hydrophilicity of the surface and maintains a wet state at a normal temperature. body.

另外,本發明還提供包括以下步驟的牙科用植體的製造方法:在鈦或鈦合金材質的牙科用植體表面形成粗糙的步驟;去除在形成所述粗糙的牙科用植體表面存在的有機污染源的步驟;以及將所述去除有機污染源的牙科用植體表面塗覆在常溫維持濕潤狀態的親水性保濕膜的步驟。 In addition, the present invention also provides a method of manufacturing a dental implant comprising the steps of: forming a rough surface on a dental implant surface of titanium or titanium alloy; removing organic substances present on the surface of the rough dental implant. a step of contaminating the source; and a step of applying the surface of the dental implant from which the organic contamination source is removed to a hydrophilic moisturizing film at a normal temperature and maintaining a wet state.

詳細說明根據本發明一較佳實施例的牙科用植體及其製備方法如下。 DETAILED DESCRIPTION OF THE INVENTION A dental implant according to a preferred embodiment of the present invention and a method of preparing the same are as follows.

首先,在本說明書中用於「植體(implant)」是表示能夠恢復喪失的人體組織的代替物,牙科用植體通常是指自然齒根脫落後齒槽骨中埋入固定裝置(fixture)以代替喪失的牙齒的齒根後,在其上部固定人工牙齒而恢復牙齒原來的功能的代替物。 First, the term "implant" as used in this specification refers to a substitute for human tissue that can recover loss. Dental implants usually refer to a fixture embedded in the alveolar bone after the natural tooth root is detached. In place of the tooth root of the lost tooth, the artificial tooth is fixed on the upper part of the tooth to restore the original function of the tooth.

特別是,在本說明書中牙科用植體的表面可以解釋為與齒槽骨結合的固定裝置的表面。具體本發明的牙科用植體可以是由鈦或者含有選自鋁、 鉭、鈮、釩、鋯、鉑、鎂中的一種以上和鈦的鈦合金形成。 In particular, the surface of the dental implant in this specification can be interpreted as the surface of the fixture associated with the alveolar bone. Specifically, the dental implant of the present invention may be made of titanium or contain aluminum, One or more of ruthenium, osmium, vanadium, zirconium, platinum, and magnesium are formed of a titanium alloy of titanium.

植體表面的性質是新生骨組織在植體表面融合的骨結合過程中的重要因素。在輕質組織內植體的穩定性決定性地由與植體表面及周邊組織邊界的相互作用和植體的形態來決定。例如,可以改變植體表面來提高對輕質組織的植體的固定性和植體的互溶性,強化植體的骨結合(osseointegration)來加速治癒過程。這種植體的骨結合可以透過植體表面的加工而改善,可以利用在植體表面形成粗糙的方法。所述粗糙通常可以以微米單位來形成。例如,微米單位的粗糙以0.1-50μm的範圍或1-30μm的範圍在植體表面形成。 The nature of the implant surface is an important factor in the process of osseointegration of new bone tissue on the surface of the implant. The stability of the implant in the light tissue is decisively determined by the interaction with the surface of the implant and the surrounding tissue and the morphology of the implant. For example, the implant surface can be altered to improve the fixation of the implants of the light tissue and the mutual solubility of the implants, and strengthen the osseointegration of the implants to accelerate the healing process. The osseointegration of the implant can be improved by processing the surface of the implant, and a rough method can be used on the surface of the implant. The roughness can generally be formed in micrometer units. For example, the roughness of the micro unit is formed on the surface of the implant in the range of 0.1-50 μm or in the range of 1-30 μm.

這種微米單位粗糙可以利用例如選自粒子噴射法(grit blasting)、吸收性噴射媒介法(resorbable blasting media)、酸蝕處理(acid etching)、鹼蝕處理(alkali etching)、鈦電漿噴塗(titanium plasma spray)、粒子噴射後酸處理法(sandblasting with large grit and acid treatment)、兩級氧化法(anodizing)、雷射表面加工法中的方法所形成。 Such micron unit roughness can be utilized, for example, selected from the group consisting of grit blasting, resorbable blasting media, acid etching, alkali etching, titanium plasma spraying ( Titanium plasma spray), sandblasting with large grit and acid treatment, two-stage oxidation (anodizing), and laser surface processing.

如上所述,經過粗面化而具有微米單位粗糙的植體的表面由於其表面積增加而具有提高植體骨結合的優點,但是具有在保存到種植手術之前的期間由於表面積大而可能增加空氣中各種污染源的污染的缺點。尤其,例如,二氧化碳、有機碳等空氣中存在的碳污染源在所述植體表面非可逆地被吸附,能夠使植體表面疏水化(hydrophobic)。植體的表面由於所述污染源被污染而疏水化的話,移植到生體內時存在於血液中的各種蛋白質無法附著到植體的表面而減少適應性,從而產生骨結合的問題,還可能誘發污染源引起的發炎反應。 As described above, the surface of the implant having a micron unit roughness after roughening has an advantage of improving the osseointegration of the implant due to an increase in its surface area, but may have an increase in air due to a large surface area during storage until the implantation operation. Disadvantages of pollution from various sources of pollution. In particular, for example, a carbon contamination source existing in air such as carbon dioxide or organic carbon is adsorbed irreversibly on the surface of the implant, and the surface of the implant can be hydrophobic. When the surface of the implant is hydrophobized due to the contamination of the contaminated source, various proteins existing in the blood when transplanted into the living body cannot adhere to the surface of the implant to reduce the adaptability, thereby causing a problem of osseointegration, and may also induce a source of contamination. The inflammatory reaction caused.

從而需要去除植體表面的有機污染源的必要,去除有機污染源的方法有,例如,向形成微米單位粗糙的植體表面照射紫外線的方法、利用電漿的方法、侵蝕方法等,其中較佳為使用照射紫外線的簡單方法。 Therefore, it is necessary to remove the organic pollution source on the surface of the implant, and the method for removing the organic pollution source is, for example, a method of irradiating ultraviolet rays to the surface of the implant having a micron unit roughness, a method using plasma, an etching method, etc., among which it is preferably used. A simple method of irradiating ultraviolet light.

根據本發明的一實施例,牙科用植體的表面形成常溫下維持濕潤狀態的親水性保濕膜,從而保存親水性。 According to an embodiment of the present invention, the surface of the dental implant forms a hydrophilic moisturizing film which maintains a wet state at normal temperature, thereby preserving hydrophilicity.

透過紫外線照射方法完全去除污染源後的植體的表面形成親水性保濕膜,在移植植體之後能夠提高與血液的親和性,從而提高與通過血液提供的各種血蛋白(例如,誘導骨結合的信號蛋白等)的親和性,最終導致提 高植體的骨結合的結果。 The surface of the implant after completely removing the pollution source by the ultraviolet irradiation method forms a hydrophilic moisturizing film, which can improve the affinity with blood after transplanting the implant, thereby improving various blood proteins (for example, inducing bone binding) provided by the blood. Affinity of protein, etc., ultimately leads to The result of osseointegration of high implants.

根據一具體實施例,所述親水性保濕膜是利用含有糖醇的溶液所形成,所述糖醇可以是選自甘油、山梨糖醇、木糖醇、甘露醇、麥芽糖醇、乳糖醇中的至少一種,親水性保濕膜可以透過將牙科用植體浸漬在親水性保濕膜中形成。 According to a specific embodiment, the hydrophilic humectant film is formed by using a solution containing a sugar alcohol, which may be selected from the group consisting of glycerin, sorbitol, xylitol, mannitol, maltitol, and lactitol. At least one, the hydrophilic moisturizing film can be formed by immersing the dental implant in a hydrophilic moisturizing film.

在此,所述溶液中包含的糖醇的總量至少為15重量%時,能夠長期維持親水性保濕膜。 Here, when the total amount of the sugar alcohol contained in the solution is at least 15% by weight, the hydrophilic moisturizing film can be maintained for a long period of time.

另外,所述溶液進一步可以含有選自由低聚殼聚糖、低聚透明質酸、膠原蛋白及凝膠所組成的群組中的功能性生物材料,藉此能夠進一步提高抗菌功能、骨形成和骨結合效能。 In addition, the solution may further contain a functional biomaterial selected from the group consisting of oligochitosan, oligomeric hyaluronic acid, collagen, and gel, thereby further enhancing antibacterial function, bone formation, and Bone binding efficacy.

根據本發明的形成有親水性保濕膜的牙科用植體及其製造方法,提高植體的血液親和性,使得有效的骨結合變得可能,因此具有能夠提高種植手術成功率,同時縮短手術期間的效果。 The dental implant formed with the hydrophilic moisturizing film according to the present invention and the method for producing the same improve the blood affinity of the implant, thereby making effective bone bonding possible, thereby improving the success rate of the implantation operation and shortening the operation period Effect.

以下藉由一個以上的具體實施例來詳細說明。但是這些實施例僅用於示例性說明,本發明的範圍並不由此限定。 The following is explained in detail by more than one specific embodiment. However, these examples are for illustrative purposes only, and the scope of the invention is not limited thereby.

實施例1:植體表面碳污染源的清除劑甘油溶液的塗覆 Example 1: Coating of carbonaceous contamination source on the surface of the implant

鈦成分植體的表面通常通過利用自動旋盤的機械加工來製造,此時表面平均粗糙約為0.2μm。在所述植體表面粒子噴射後利用酸處理(SA法)來將植體表面的平均粗糙調整為約20μm。 The surface of the titanium component implant is usually manufactured by mechanical processing using an automatic rotary disk, in which case the surface average roughness is about 0.2 μm. The average roughness of the implant surface was adjusted to about 20 μm by acid treatment (SA method) after the implant surface particles were sprayed.

之後,向形成所述粗糙的植體照射10分鐘的紫外線以清除碳污染源,將清除碳污染源的植體浸漬到50重量%的甘油溶液中取出,並在植體的固定部分均勻塗覆甘油。 Thereafter, the rough-formed implants were irradiated with ultraviolet rays for 10 minutes to remove the carbon contamination source, the plants from which the carbon contamination source was removed were immersed in a 50% by weight glycerin solution, and glycerin was uniformly coated on the fixed portion of the implant.

此時,用於正常老化實驗的植體和加速老化實驗的植體都維持相同的溶液溫度和周邊溫度、溶液濃度等的條件下,形成甘油保濕膜。 At this time, the implant for the normal aging test and the accelerated aging test were maintained under the same solution temperature, ambient temperature, solution concentration, etc., to form a glycerin humectant film.

另外,還準備了使用進一步含有5重量%的低聚殼聚糖的甘油溶液形成保濕膜的正常老化試驗用及加速老化實驗用植體。 Further, a normal aging test and an accelerated aging test implant using a glycerin solution further containing 5% by weight of oligochitosan to form a moisturizing film were prepared.

如上製造的塗覆有甘油溶液的植體在以下實施例2和4中使用。 The glycerin-coated implants manufactured as above were used in the following Examples 2 and 4.

實施例2:正常老化的塗覆有甘油保濕膜的植體的血液蛋白質附著能及 血液親和性實驗 Example 2: Blood protein adhesion of normally aged glycerin moisturizing film-coated implants and Blood affinity test

將所述實施例1中製造之用於正常老化實驗的塗覆有甘油溶液的植體及塗覆含有低聚殼聚糖的甘油溶液的植體分別在常溫(約25℃)下放置2週及4週後,浸漬到含有血液蛋白(白蛋白、球蛋白、血清)的溶液中,然後觀察附著到植體表面的血液蛋白的程度。 The implants coated with the glycerin solution and the glycerin solution containing the oligochitosan solution prepared in the above-mentioned Example 1 for normal aging experiments were respectively placed at room temperature (about 25 ° C) for 2 weeks. After 4 weeks, it was immersed in a solution containing blood proteins (albumin, globulin, serum), and then the extent of blood proteins attached to the surface of the implant was observed.

此時,對照組使用沒有塗覆甘油溶液但是清除了碳污染源的植體,對比實驗組使用塗覆蒸餾水並清除碳污染源的植體和清除碳污染源的植體表面均勻塗覆HEPES緩衝溶液的植體。 At this time, the control group used an implant that did not coat the glycerin solution but cleared the carbon contamination source. In the comparative experimental group, the implanted distilled water and the carbon contamination source were removed and the surface of the implant from which the carbon contamination source was removed was uniformly coated with the HEPES buffer solution. body.

如第1圖所示,即使經過4週長時間的老化,塗覆甘油溶液的植體及塗覆含有低聚殼聚糖的甘油溶液的植體維持血液蛋白質的附著能。 As shown in Fig. 1, the implant coated with the glycerin solution and the implant coated with the glycerin solution containing oligochitosan maintained the adhesion energy of blood proteins even after aging for 4 weeks.

相反,塗覆已知具有優異的水分保留能力的HEPES的植體隨著時間的推移血液蛋白的附著能減少。 In contrast, coating of HEPES known to have excellent moisture retention ability reduces the adhesion of blood proteins over time.

此處,第1圖的圖表中CC表示清除碳污染源的植體,DIW表示蒸餾水、GC表示甘油、OCS表示低聚殼聚糖。 Here, in the graph of Fig. 1, CC denotes an implant which removes a carbon contamination source, DIW denotes distilled water, GC denotes glycerin, and OCS denotes oligochitosan.

此外,將常溫下放置4週的所述植體分別浸漬到血液中,觀察了血液親和性。 Further, the implants placed at normal temperature for 4 weeks were each immersed in blood, and blood affinity was observed.

如第2圖所示,在塗覆甘油溶液的植體及塗覆含有低聚殼聚糖的甘油溶液的植體中,血液滲入到植體的固定部分上部,因此用肉眼就可以確認血液親和性高,而塗覆HEPES的植體肉眼觀察血液親和性相對不高。 As shown in Fig. 2, in the implant coated with the glycerin solution and the implant coated with the oligochitosan-containing glycerin solution, the blood penetrates into the upper portion of the fixed portion of the implant, so that blood affinity can be confirmed with the naked eye. The sex is high, while the HEPES-coated implants have a relatively low blood affinity observed by the naked eye.

實施例3:塗覆加速老化的甘油保濕膜的植體的血液蛋白附著能及血液親和性實驗。 Example 3: Blood protein adhesion energy and blood affinity test of an implant coated with an accelerated aged glycerin moisturizing film.

將實施例1中製造之用於加速老化實驗的塗覆甘油溶液的植體及塗覆含有低聚殼聚糖的甘油溶液的植體分別在高溫乾燥條件(55℃)下放置3週。這換算成常溫下正常老化時間的話相當於約6個月的老化時間。嗣後,將所述植體分別浸漬在含有與實施例2相同的血液蛋白的溶液中,觀察植體表面附著的血液蛋白質的程度。 The glycerin-coated implants prepared in Example 1 and the glycerin solution containing the oligochitosan solution were each placed under high temperature drying conditions (55 ° C) for 3 weeks. This is equivalent to an aging time of about 6 months when converted to normal aging time at normal temperature. After the sputum, the implants were each immersed in a solution containing the same blood protein as in Example 2, and the degree of blood protein attached to the surface of the implant was observed.

此時,對照組使用沒有清除碳污染源的植體,對照組使用沒有塗覆甘油溶液的清除碳污染源的植體。 At this time, the control group used an implant that did not have a carbon contamination source, and the control group used an implant that did not coat the glycerin solution to remove the carbon contamination source.

如第3a圖和第3b圖所示,即使在高溫乾燥加速老化條件下放置3週而表面老化,但是由於是濕潤狀態而能維持深灰色的表面顏色,確認塗覆甘 油溶液的植體和塗覆含有低聚殼聚糖的甘油溶液的植體能夠維持血液蛋白的附著能。 As shown in Fig. 3a and Fig. 3b, even if the surface is aged for 3 weeks under high temperature drying accelerated aging conditions, the surface color of the dark gray can be maintained due to the wet state, and it is confirmed that the coating is sweet. The implant of the oil solution and the implant coated with the glycerol solution containing the oligochitosan can maintain the adhesion energy of the blood protein.

相反,沒有塗覆甘油溶液而清除碳污染源的植體在加速老化的條件下放置後,確認蛋白的附著能幾乎消失。 On the contrary, after the implants which were not coated with the glycerin solution and the carbon contamination source were removed under accelerated aging conditions, it was confirmed that the adhesion energy of the protein almost disappeared.

另外,將在高溫條件下放置3週的所述植體分別浸在血液中觀察了血液親和性。 In addition, blood affinity was observed by immersing the implants placed under high temperature for 3 weeks in the blood.

如第4圖所示,塗覆甘油溶液的植體及塗覆含有低聚殼聚糖的甘油溶液的植體能夠確認與實施例2相同的高血液親和性,肉眼觀察到沒有塗覆甘油溶液而清除碳污染源的植體的血液親和性顯然不怎麼高。 As shown in Fig. 4, the implant coated with the glycerin solution and the implant coated with the glycerol solution containing the oligochitosan were able to confirm the same high blood affinity as in Example 2, and the glycerin solution was not observed by the naked eye. The blood affinity of the implants that remove carbon sources is clearly not very high.

實施例4:加速老化的維持或去除保濕膜的植體的鬆開力矩(removal torgue)的比較實驗 Example 4: Comparative experiment of releasing torgue of an implant that maintains or removes a moisturizing membrane

根據實施例2和實施例3,正常老化實驗和加速老化實驗模式中,確認了塗覆甘油溶液的植體及塗覆含有低聚殼聚糖的甘油溶液的植體能夠很好地維持血液蛋白附著能和血液親和性。 According to Example 2 and Example 3, in the normal aging test and the accelerated aging test mode, it was confirmed that the implant coated with the glycerin solution and the implant coated with the oligochitosan-containing glycerin solution can well maintain the blood protein. Adhesion energy and blood affinity.

但是,由於實施例2和實施例3是體外(in-vitro)實驗,因此為了驗證實際上塗覆甘油溶液的植體及塗覆含有低聚殼聚糖的甘油溶液的植體移植到人體內時是否發揮同等效果,需要做體內(in-vivo)實驗。即,需要對植體表面的保濕膜是否作為骨結合的阻礙因素而起作用進行驗證。 However, since Example 2 and Example 3 are in-vitro experiments, in order to verify that the implant actually coated with the glycerin solution and the implant coated with the oligochitosan-containing glycerin solution are implanted into the human body, Whether to play the same effect, you need to do an in-vivo experiment. That is, it is necessary to verify whether or not the moisturizing film on the surface of the implant functions as a hindrance factor for bone bonding.

實施例4中將塗覆有含10重量%、25重量%、50重量%的甘油的溶液的植體在高溫條件(約55℃)下放置80天和120天。這換算成常溫下正常老化時間的話相當於約2年和3年的老化時間。 In Example 4, the implant coated with a solution containing 10% by weight, 25% by weight, and 50% by weight of glycerin was allowed to stand under high temperature conditions (about 55 ° C) for 80 days and 120 days. This is equivalent to an aging time of about 2 years and 3 years when converted to normal aging time at normal temperature.

將經過這種加速老化過程的植體移植到微型豬的齒槽骨。此時,對照組使用沒有清除碳污染源的植體(SA)、對比實驗組使用沒有塗覆甘油溶液並清除碳污染源的SA植體(CC)移植到微型豬的齒槽骨中。 The implant undergoing this accelerated aging process is transplanted to the alveolar bone of the miniature pig. At this time, the control group used the implant (SA) which did not remove the carbon pollution source, and the comparative experiment group transplanted into the alveolar bone of the miniature pig using the SA implant (CC) which was not coated with the glycerin solution and cleared the carbon contamination source.

第5圖是去除種植手術後經過16天的骨結合時間的植體時測得的鬆開力矩的圖表,鬆開力矩越高說明植體的骨結合越好。 Figure 5 is a graph showing the release torque measured after removal of the implant for 16 days of osseointegration time after implantation. The higher the release torque, the better the bone binding of the implant.

如第5圖所示,除了清除碳污染源後在沒有額外的塗覆過程而經過加速老化過程的植體(CC,老化2年)和加速老化2年中保濕膜乾燥的塗覆含有10重量%的甘油的植體(CC+GC10,老化2年)之外,塗覆含有25重量%以上的甘油的保濕膜的植體都具有與清除碳污染源的植體(CC)相同水準的 鬆開力矩。 As shown in Fig. 5, the coating of the moisturizing film is dried in an amount of 10% by weight in the implant (CC, aging for 2 years) and accelerated aging for 2 years, except for the removal of the carbon source, after the accelerated aging process. In addition to the glycerol implant (CC+GC10, aged for 2 years), the implants coated with the humectant film containing 25% by weight or more of glycerin have the same level as the implant (CC) from which the carbon contamination source is removed. Loosen the torque.

以上述實驗結果為基礎,系統分析塗覆含有10重量%、25重量%、50重量%的甘油的植體之間的鬆開力矩的情況,能夠得到使用含有至少15重量%以上的甘油的溶液塗覆植體,能夠確保有效的親水性保濕膜性能。 Based on the above experimental results, the system analyzes the release torque between the implants containing 10% by weight, 25% by weight, and 50% by weight of glycerin, and it is possible to obtain a solution containing at least 15% by weight or more of glycerin. Coating the implant ensures an effective hydrophilic humectant film performance.

從而,確認塗覆甘油溶液形成的保濕膜能夠維持植體相當長時間的血液蛋白質附著能和血液親和性,也並不作為骨結合的阻礙要素而作用。 Therefore, it was confirmed that the moisturizing film formed by coating the glycerin solution can maintain the blood protein adhesion energy and blood affinity for the implant for a long period of time, and does not function as a barrier element of osseointegration.

第1圖是在常溫下正常老化一具體實施例之塗覆有保濕膜的植體的血液蛋白附著能的評價結果(其中,CC:清除碳、DIW:去離子水、HEPES:有機化學緩衝劑、GC:甘油、OCS:低聚殼聚糖、GC/OCS:甘油/低聚殼聚糖);第2圖是在常溫下正常老化一具體實施例之塗覆有保濕膜的植體的血液親和性的評價結果;第3a圖及第3b圖是在55℃下加速老化一具體實施例之塗覆有保濕膜的植體的血液蛋白附著能的評價結果;第4圖是在55℃下加速老化一具體實施例之塗覆有保濕膜的植體的血液親和性的評價結果;以及第5圖是在55℃下加速老化一具體實施例之塗覆有保濕膜的植體種植到微型豬下顎後經骨結合期間後評價鬆開力矩的動物實驗結果(GC10:10重量%甘油、GC25:25重量%甘油、GC50:50重量%甘油)。 Fig. 1 is a result of evaluation of blood protein adhesion energy of a moisturizing film-coated implant of a specific example at normal temperature (where CC: carbon removal, DIW: deionized water, HEPES: organic chemical buffer) , GC: glycerol, OCS: oligochitosan, GC/OCS: glycerol/oligomeric chitosan); Fig. 2 is the blood of a humectant-coated implant in a specific embodiment which is normally aged at normal temperature. Evaluation results of affinity; Figures 3a and 3b are evaluation results of blood protein adhesion energy of a moisturizing film-coated implant according to a specific example of accelerated aging at 55 ° C; Figure 4 is at 55 ° C Accelerated aging - evaluation of blood affinity of a humectant-coated implant of a specific embodiment; and Figure 5 is accelerated aging at 55 ° C. A specific embodiment of a humectant-coated implant is planted to a micro Animal test results of the release torque after the osseointegration of the pigs (GC10: 10% by weight glycerol, GC25: 25% by weight glycerol, GC50: 50% by weight glycerol).

Claims (11)

一種具親水性保濕膜塗覆的牙科用植體,包括:一鈦或鈦合金材質的粗糙表面的牙科用植體;以及在所述牙科用植體表面形成並保存所述表面的親水性,在常溫下維持濕潤狀態的親水性保濕膜。 A dental implant coated with a hydrophilic moisturizing film, comprising: a dental implant having a rough surface of titanium or titanium alloy; and forming and preserving hydrophilicity of the surface on the surface of the dental implant, A hydrophilic moisturizing film that maintains a wet state at normal temperature. 依據申請專利範圍第1項所述之具親水性保濕膜塗覆的牙科用植體,其中所述親水性保濕膜由含有糖醇的溶液所形成。 A dental implant coated with a hydrophilic moisturizing film according to claim 1, wherein the hydrophilic moisturizing film is formed of a solution containing a sugar alcohol. 依據申請專利範圍第2項所述之具親水性保濕膜塗覆的牙科用植體,其中所述糖醇係選自由甘油、山梨糖醇、木糖醇、甘露醇、麥芽糖醇與乳糖醇組成的群組中的至少一種。 A dental implant coated with a hydrophilic moisturizing film according to claim 2, wherein the sugar alcohol is selected from the group consisting of glycerin, sorbitol, xylitol, mannitol, maltitol and lactitol At least one of the groups. 依據申請專利範圍第3項所述之具親水性保濕膜塗覆的牙科用植體,其中所述溶液中含有的糖醇的總量至少為15重量%。 A dental implant coated with a hydrophilic moisturizing film according to claim 3, wherein the total amount of the sugar alcohol contained in the solution is at least 15% by weight. 依據申請專利範圍第2項所述之具親水性保濕膜塗覆的牙科用植體,其中所述溶液進一步含有選自由低聚殼聚糖、低聚透明質酸、膠原蛋白與凝膠所組成的群組中的物質。 A dental implant coated with a hydrophilic moisturizing film according to claim 2, wherein the solution further comprises a component selected from the group consisting of oligomeric chitosan, oligomeric hyaluronic acid, collagen and gel. The substance in the group. 一種具親水性保濕膜塗覆的牙科用植體的製造方法,該方法的步驟包括:在鈦或鈦合金材質的牙科用植體表面形成粗糙的步驟;去除在形成所述粗糙的牙科用植體表面存在的有機污染源的步驟;以及將所述去除有機污染源的牙科用植體表面塗覆在常溫維持濕潤狀態的親水性保濕膜的步驟。 A method for producing a dental implant coated with a hydrophilic moisturizing film, the method comprising the steps of: forming a rough surface on a dental implant surface of titanium or titanium alloy; removing the dental implant forming the roughness a step of presenting an organic contamination source on the surface of the body; and a step of applying the surface of the dental implant from which the organic contamination source is removed to a hydrophilic humectant film maintained at a normal temperature. 依據申請專利範圍第6項所述之具親水性保濕膜塗覆的牙科用植體的製造方法,其中所述親水性保濕膜係將所述牙科用植體浸漬到含有糖醇的溶液中形成。 A method for producing a dental implant coated with a hydrophilic moisturizing film according to claim 6, wherein the hydrophilic moisturizing film is formed by dipping the dental implant into a solution containing a sugar alcohol. . 依據申請專利範圍第7項所述之具親水性保濕膜塗覆的牙科用植體的製 造方法,其中所述糖醇係選自由甘油、山梨糖醇、木糖醇、甘露醇、麥芽糖醇與乳糖醇所組成群組中的至少一種。 Preparation of a dental implant coated with a hydrophilic moisturizing film according to claim 7 of the patent application scope The method, wherein the sugar alcohol is at least one selected from the group consisting of glycerin, sorbitol, xylitol, mannitol, maltitol and lactitol. 依據申請專利範圍第8項所述之具親水性保濕膜塗覆的牙科用植體的製造方法,其中所述溶液中含有的糖醇的總量至少為15重量%。 A method for producing a dental implant coated with a hydrophilic moisturizing film according to claim 8, wherein the total amount of the sugar alcohol contained in the solution is at least 15% by weight. 依據申請專利範圍第7項所述之具親水性保濕膜塗覆的牙科用植體的製造方法,其中所述溶液進一步含有選自由低聚殼聚糖、低聚透明質酸、膠原蛋白與凝膠所組成的群組中的物質。 A method for producing a dental implant coated with a hydrophilic moisturizing film according to claim 7, wherein the solution further comprises an oligochitosan, an oligomeric hyaluronic acid, a collagen and a condensed solution. The substance in the group consisting of glue. 依據申請專利範圍第6項所述之具親水性保濕膜塗覆的牙科用植體的製造方法,其中所述牙科用植體表面的粗糙可以利用粒子噴射法(grit blasting)、吸收性噴射媒介法(resorbable blasting media)、酸蝕處理(acid etching)、堿蝕處理(alkali etching)、鈦等離子噴塗(titanium plasma spray)、粒子噴射後酸處理法(sandblasting with large grit and acid treatment)、兩級氧化法(anodizing)或鐳射表面加工法中的方法形成。 A method for producing a dental implant coated with a hydrophilic moisturizing film according to claim 6, wherein the roughening of the surface of the dental implant can utilize a particle blasting method or an absorbent jet medium. Resorbable blasting media, acid etching, alkali etching, titanium plasma spray, sandblasting with large grit and acid treatment, two-stage Formed by anodizing or laser surface processing.
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