TW202202145A - Medicine of organogermanium for wound healing and method of using the same - Google Patents

Medicine of organogermanium for wound healing and method of using the same Download PDF

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TW202202145A
TW202202145A TW109123489A TW109123489A TW202202145A TW 202202145 A TW202202145 A TW 202202145A TW 109123489 A TW109123489 A TW 109123489A TW 109123489 A TW109123489 A TW 109123489A TW 202202145 A TW202202145 A TW 202202145A
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wound healing
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promoting wound
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黃慶村
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Abstract

A medicine for wound healing, which promotes wound healing by inducing interferon production of a body. Forms of the medicine include powders, ointments, emulsions, liquids, etc., which can promote rapid healing of various skin wounds and ulcers in the body. There is no obvious exudate from the wound during the healing process. The tissue surface recovers and is smooth after the healing process, and almost no scar is left. The invention also discloses a method of using the above-mentioned medicine.

Description

促進傷口癒合的有機鍺藥物及其使用方法Organic germanium medicine for promoting wound healing and using method thereof

本發明涉及一種促進傷口癒合的藥物,可用於治療手術切口、創傷、撕裂傷、磨損傷、刀傷、燒傷、燙傷、褥瘡以及潰瘍等的癒合。The invention relates to a medicine for promoting wound healing, which can be used for the healing of surgical incisions, wounds, lacerations, abrasion injuries, cuts, burns, scalds, bedsores and ulcers.

造成傷口的原因很多,除了創傷、撕裂傷、磨損傷、刀傷、燒傷、燙傷、糖尿病潰瘍以及長期臥床所引起的褥瘡等皮膚傷口外,體內的潰瘍也是常見的傷口。There are many reasons for wounds. In addition to skin wounds such as wounds, lacerations, abrasion injuries, knife wounds, burns, scalds, diabetic ulcers and bedsores caused by long-term bed rest, ulcers in the body are also common wounds.

傷口的癒合是一個複雜而緩慢的過程,新的上皮組織和結締組織是由治療中的創傷細胞的遷移和增殖所形成,因此促進細胞遷移、分化和增殖等的作用,有助於傷口的癒合。先前研究表明,包括表皮生長因子(epidermal growth factor, EGF)、轉化生長因子-α (transforming growth factor-α,TGF-α)以及肝素結合表皮生長因子(HB-EGF)等的所謂「表皮生長因子族群(EGF family)」,被認為是在傷口邊緣調節角質形成細胞增殖的關鍵(Paul Martin,”Wound Healing-Aiming for Perfect Skin Regeneration”, p75-81, SCIENCE, Vol.276,4 April,1997),會在表皮損傷部位大量釋放。Wound healing is a complex and slow process. New epithelial tissue and connective tissue are formed by the migration and proliferation of wound cells during treatment, thus promoting cell migration, differentiation and proliferation, etc., which are helpful for wound healing. . Previous studies have shown that so-called "epidermal growth factors" including epidermal growth factor (EGF), transforming growth factor-α (TGF-α), and heparin-binding epidermal growth factor (HB-EGF), etc. "EGF family", considered to be the key to regulating keratinocyte proliferation at the wound edge (Paul Martin, "Wound Healing-Aiming for Perfect Skin Regeneration", p75-81, SCIENCE, Vol.276, 4 April, 1997) , will be released in large quantities at the site of epidermal damage.

此外,研究也發現,外源性的表皮生長因子和轉化生長因子-α應用到豬背的燒傷部位,會增強其表皮細胞的再生(G. L. Brown et al., J. Exp. Med. 163, 1319 (1986); G.S. Schultz et al., Science 235, 350 (1987))。這些生長因子作用於表皮時,可作為細胞移動原(motogens)與促細胞分裂原(mitogens)而驅動傷口的閉合(Y. Barrandon and H. Green, Cell 50, 1131 (1987))。In addition, studies have also found that exogenous epidermal growth factor and transforming growth factor-α applied to the burn site of pig back can enhance the regeneration of epidermal cells (GL Brown et al., J. Exp. Med. 163, 1319 (1986); GS Schultz et al., Science 235, 350 (1987)). When these growth factors act on the epidermis, they act as motogens and mitogens to drive wound closure (Y. Barrandon and H. Green, Cell 50, 1131 (1987)).

先前關於各種細胞因子(cytokine)和肽生長因子(peptide growth factors)對腸上皮細胞(intestinal epithelial cell)復原的體外模型研究(Diagnass, A. U., Podolsky, D. K., Gastroenterology, 1993, 105(5):1323-1332)結果顯示:轉化生長因子-α、表皮生長因子、白細胞介素-1β (interleukin -1β,IL-1β)和干擾素-γ (interferon-γ,IFN-γ)等4因子,促進了具生物活性的TGF-β1肽(bioactive TGF-β1 peptide)在受傷的IEC-6腸單層細胞膜上的產生,並使腸上皮細胞傷口的復原增強了2.3倍至5.5倍。Previous in vitro model studies on the recovery of intestinal epithelial cells by various cytokines and peptide growth factors (Diagnass, AU, Podolsky, DK, Gastroenterology, 1993, 105(5):1323 -1332) results showed that four factors, including transforming growth factor-α, epidermal growth factor, interleukin-1β (interleukin-1β, IL-1β) and interferon-γ (interferon-γ, IFN-γ), promoted the Production of bioactive TGF-β1 peptide on wounded IEC-6 intestinal monolayer cell membranes enhanced intestinal epithelial wound healing by 2.3- to 5.5-fold.

在先前的技藝中,一些促進傷口癒合的藥劑是以生長因子為主要成分,但外源性的生長因子治療傷口存在以下的缺點:(一)生長因子是不穩定的蛋白質,儲存時即容易分解,採用口服給藥時,在進入血液之前即會被消化和破壞;(二)生長因子被人體吸收的速率緩慢,並會被迅速分解,因此,外敷的軟膏劑之使用效果也有限;(三)許多生長因子是特定性物種(species specific),如由腸胃外給藥,會被識別為外來物種而被排斥,引發危險的免疫反應。居於以上原因,外源性的生長因子並不是理想的傷口癒合藥物。有文獻也指出:沒有證據表明通過胃腸外給藥的生長因子會到達皮膚、結締組織和支持組織。In the prior art, some agents for promoting wound healing are mainly composed of growth factors, but exogenous growth factors have the following disadvantages in the treatment of wounds: (1) Growth factors are unstable proteins that are easily decomposed during storage , when administered orally, it will be digested and destroyed before entering the blood; (2) the growth factor is absorbed slowly by the human body, and will be rapidly decomposed, therefore, the use effect of externally applied ointment is also limited; (3) ) Many growth factors are species specific and, if administered parenterally, are recognized as foreign and rejected, triggering a dangerous immune response. For the above reasons, exogenous growth factors are not ideal wound healing drugs. The literature also states that there is no evidence that parenterally administered growth factors reach the skin, connective and supportive tissues.

本發明提供一種促進傷口癒合的藥物,其可誘發體內產生干擾素-γ (interferon gamma,IFN-γ),促進體內產生TGF-β1肽,並進而加速傷口癒合。The invention provides a medicine for promoting wound healing, which can induce the production of interferon-γ (IFN-γ) in vivo, promote the production of TGF-β1 peptide in vivo, and then accelerate wound healing.

本發明還提供一種使用前述藥物使其促進傷口癒合的效果得以有效發揮的方法。The present invention also provides a method for effectively exerting the effect of promoting wound healing by using the aforementioned medicament.

本發明所提供的促進傷口癒合的藥物其係以能刺激體內產生干擾素的有機鍺化合物為主要成分。The medicine for promoting wound healing provided by the present invention is mainly composed of an organic germanium compound which can stimulate the production of interferon in the body.

本發明因採用有機鍺化合物,而有機鍺化合物具有抗菌、消炎、鎮痛等作用,因此施用於傷口癒合治療時,可以同時產生消毒、消炎、鎮痛的作用。本發明還可以解決外源性生長因子癒合傷口所遭遇的困難。而經證實,本發明促進傷口癒合的藥物與先前的藥劑比較具有以下的效益:(一)可抑制滲出液的產生,傷口易於保持乾淨,大幅減少醫護的負擔與患者的痛苦;(二)適合對開放性或較大傷口的癒合治療,並且癒合迅速;(三)幾乎不留疤痕,適合於醫學美容手術傷口的癒合;(四)適合因糖尿病或長期臥床所引起的皮膚傷口癒合之促進。Because the present invention adopts organic germanium compound, and the organic germanium compound has antibacterial, anti-inflammatory, analgesic and other effects, so when applied to wound healing treatment, it can simultaneously produce the effects of disinfection, anti-inflammatory and analgesic. The present invention can also solve the difficulties encountered by exogenous growth factors in healing wounds. And it has been confirmed that the medicine for promoting wound healing of the present invention has the following benefits compared with the previous medicines: (1) it can inhibit the production of exudate, the wound is easy to keep clean, and the burden of medical care and the pain of patients is greatly reduced; (2) it is suitable for Healing treatment of open or large wounds, and the healing is rapid; (3) It leaves almost no scars, suitable for the healing of medical cosmetic surgery wounds; (4) It is suitable for the promotion of skin wound healing caused by diabetes or long-term bed rest.

為讓本發明之上述和其他目的、特徵和優點能更明顯易懂,下文特舉實施例,並配合所附圖式,作詳細說明如下。In order to make the above-mentioned and other objects, features and advantages of the present invention more obvious and easy to understand, the following specific embodiments are given and described in detail in conjunction with the accompanying drawings.

本發明揭示具上述傷口癒合藥理的藥物包括但不限於以下幾種類型之有機鍺化合物:(一) 雙-羧烷基鍺倍半氧化物(bis-carboxyalkyl germanium sesquioxide)與其衍生物、(二) 鍺烷化合物(germanes)、(三) 雜氮三環鍺化合物(germatranes)、(四) 螺旋鍺化合物(spirogermanium compound)、(五) 鍺卟啉化合物(germanium porphyrines)以及(六) 二茂鍺化合物(germanocenes)。(一)~(四)進一步說明如下。The drugs with the above-mentioned wound healing pharmacology disclosed in the present invention include but are not limited to the following types of organic germanium compounds: (1) bis-carboxyalkyl germanium sesquioxide and its derivatives, (2) Germane compounds (germanes), (three) azatricyclic germanium compounds (germatranes), (four) spirogermanium compounds, (five) germanium porphyrines and (six) germanocene compounds (germanocenes). (1) to (4) are further explained as follows.

(一) 雙-羧烷基鍺倍半氧化物(bis-carboxyalkyl germanium sesquioxide)與其衍生物: 此類有機鍺化合物之化學代表式如下:

Figure 02_image001
上式中之R1、R2、R3為H、取代或未取代的低碳烷基(alkyl)如甲基(methyl)或乙基(ethyl)等、芳基(aryl)、雜芳基(hetaryl)、取代或未取代的胺基(amino group)或醯胺基(amido group)等;X為羥基(OH)、O-Na、O-K、鹼性胺基(basic amino group)、芳基(aryl)或雜芳基(hetaryl)等。(1) bis-carboxyalkyl germanium sesquioxide and its derivatives: The chemical representation of such organic germanium compounds is as follows:
Figure 02_image001
R1, R2, R3 in the above formula are H, substituted or unsubstituted lower alkyl (alkyl) such as methyl (methyl) or ethyl (ethyl), etc., aryl (aryl), heteroaryl (hetaryl) , substituted or unsubstituted amino group (amino group) or amide group (amido group), etc.; X is hydroxyl (OH), O-Na, OK, basic amino group (basic amino group), aryl (aryl) Or heteroaryl (hetaryl) and the like.

此類有機鍺化合物中最具代表性、最被廣泛研究與應用的是雙-羧乙基鍺倍半氧化物(bis-carboxyethyl germanium sesquioxide,Ge-132),其具有高水溶性及免疫活性。Among such organic germanium compounds, the most representative and most widely studied and applied is bis-carboxyethyl germanium sesquioxide (Ge-132), which has high water solubility and immunological activity.

(二) 鍺烷化合物(germanes): 代表分子式如下:

Figure 02_image002
式中之R1、R2、R3為H、取代或未取代的低碳烷基(alkyl)如甲基(methyl)或乙基(ethyl)等;R4為烷基;X為取代或未取代的醣苷基(glycosyl group)。(2) Germane compounds (germanes): The representative molecular formula is as follows:
Figure 02_image002
R1, R2, R3 in the formula are H, substituted or unsubstituted lower alkyl (alkyl) such as methyl (methyl) or ethyl (ethyl), etc.; R4 is alkyl; X is substituted or unsubstituted glycoside base (glycosyl group).

此類化合物中最具代表性的是代號GeOH的6-O-3-三甲基鍺烷-丙基-β-D-吡喃葡萄醣苷(6-O-[3-(trimethyl-germyl)propyl]-β-D- glucopyranoside),研究表明其水溶性與免疫活性均高於Ge-132。The most representative of such compounds is 6-O-3-trimethylgermane-propyl-β-D-glucopyranoside (6-O-[3-(trimethyl-germyl)propyl) codenamed GeOH. ]-β-D-glucopyranoside), studies have shown that its water solubility and immune activity are higher than Ge-132.

(三) 雜氮三環鍺化合物(germatranes): 具免疫活性的雜氮三環鍺化合物,其分子結構代表式包括但不限於下式:

Figure 02_image003
式中之R為苯基(benzyl group)或苯溴基(bromobenzyl group)、肉桂酸基([-CH(C6 H4 OH)CH2 COOH])、咖啡酸基([-CH(C6 H3 (OH)2 )CH2 COOH])等,這些雜氮三環鍺化合物也皆已被證明具有低毒性和良好的免疫活性。(3) Aza-azatricyclic germanium compounds (germatranes): immunologically active aza-azatricyclic germanium compounds, the representative formula of its molecular structure includes but is not limited to the following formula:
Figure 02_image003
R in the formula is phenyl group (benzyl group) or phenyl bromide group (bromobenzyl group), cinnamic acid group ([-CH(C 6 H 4 OH)CH 2 COOH]), caffeic acid group ([-CH(C 6 ) H 3 (OH) 2 )CH 2 COOH]), etc., these aza-tricyclic germanium compounds have also been proved to have low toxicity and good immune activity.

(四) 螺旋鍺化合物(spirogermanium compound): 具免疫刺激性之螺旋鍺化合物,包括但不限於3-(2, 8, 9-trioxa-aza-1-germatricyclo [3. 3. 3. 0] undecane-1-yl)-caffeic Acid、4,4-dialkyl-4-germacyclohexanon或8,8-dialkyl-8-germaazaspiro(4,5)decan等。(4) Spirogermanium compound: Immunostimulatory helical germanium compounds, including but not limited to 3-(2, 8, 9-trioxa-aza-1-germatricyclo[3.3.3.0] undecane-1-yl)-caffeic Acid, 4, 4-dialkyl-4-germacyclohexanon or 8,8-dialkyl-8-germaazaspiro(4,5)decan etc.

以上各種有機鍺化合物((一)~(六))的抗腫瘤、免疫調節、干擾素誘導等特性一直倍受注目。其中雙-羧乙基鍺倍半氧化物以及其衍生物早就被發現具有鎮痛作用(analgesic action)、抗炎作用(anti-inflammatory action)、抗氧化(antioxidant effect)作用與抗缺氧作用(antihyproxic effect) (V. G. Lakhtin , N. G. Komalenkova, V. G. Bykovchenko, G. N. Yakovleva, E. A. Chernyshev, Synthesis and application of organogermanium compounds, Polymer Science Series D, Volume 4, Issue 3 , pp 221-227, 2011-07-01)、免疫調節作用(immunomodulating action)、抗病毒作用(antiviral action)作用(L. G. Menchikov1 and M. A. Ignatenko, Biological Activity of Organogermanium Compounds (A Review), Pharmaceutical Chemistry Journal, Vol. 46, No. 11, February, 2013;D. W. Niesel、C. B. Hess、Y. J. Cho、K. D. Klimpel and G. R. Klimpel,Infection and Immunity, June 1986, p. 828-833 Vol. 52, No. 3)。The above-mentioned various organogermanium compounds ((1)-(6)) have been attracting much attention for their anti-tumor, immunomodulatory, and interferon-inducing properties. Among them, bis-carboxyethylgermanium sesquioxide and its derivatives have long been found to have analgesic action, anti-inflammatory action, antioxidant effect and antihypoxia effect ( antihyproxic effect) (VG Lakhtin, NG Komalenkova, VG Bykovchenko, GN Yakovleva, EA Chernyshev, Synthesis and application of organogermanium compounds, Polymer Science Series D, Volume 4, Issue 3, pp 221-227, 2011-07-01), Immunology Immunomodulating action, antiviral action (LG Menchikov1 and MA Ignatenko, Biological Activity of Organogermanium Compounds (A Review), Pharmaceutical Chemistry Journal, Vol. 46, No. 11, February, 2013; DW Niesel , CB Hess, YJ Cho, KD Klimpel and GR Klimpel, Infection and Immunity, June 1986, p. 828-833 Vol. 52, No. 3).

研究表明,讓小鼠口服劑量300 mg / kg 的Ge-132後,在20小時的小鼠血清中檢測到顯著水平的干擾素活性,在24小時時干擾素活性達到最大值320U/ml(Hisashi ASO;Fujio SUZUKI;Takahiro YAMAGUCHI; Yoshiro HAYASHI;Takusaburo EBINA and Nakao ISHIDA, Microbiol. Immunol. Vol. 29 (1), 65-74, 1985)。Ge-132基本上不具毒性(Asai K., Miracle Cure: Organic Germanium. New York: Japan Publications/ Kodansha International via Harper and Row, 1980;Stephen A. Levine, Journal of Orthomolecular Medicine, (1987) Vol. 2 No. 2, 83-87;Takashi Nakamura、Taizo Nagura、Katsuyuki Sato and Masao Ohnishi, Biosci. Microbiota Food Health, 31(2): 37–45 (2012)),相對於其他有機鍺化合物具有較高的水溶性,是最具代表性,並被廣泛研究與使用的有機鍺化合物,除已被使用作為消炎劑、鎮痛劑(日本公開特許公報昭62-93293)、熱傷治療劑(日本特開2002–193802)、免疫刺激劑等外,也被用為身體健康補充劑,廣泛添加於保健品與化妝品中。雖然如此,但此前從未曾被當作促進傷口癒合的主要藥劑。Studies have shown that after giving mice an oral dose of 300 mg/kg of Ge-132, significant levels of interferon activity were detected in mouse serum at 20 hours, and the interferon activity reached a maximum of 320 U/ml at 24 hours (Hisashi ASO; Fujio SUZUKI; Takahiro YAMAGUCHI; Yoshiro HAYASHI; Takusaburo EBINA and Nakao ISHIDA, Microbiol. Immunol. Vol. 29(1), 65-74, 1985). Ge-132 is not substantially toxic (Asai K., Miracle Cure: Organic Germanium. New York: Japan Publications/ Kodansha International via Harper and Row, 1980; Stephen A. Levine, Journal of Orthomolecular Medicine, (1987) Vol. 2 No. . 2, 83-87; Takashi Nakamura, Taizo Nagura, Katsuyuki Sato and Masao Ohnishi, Biosci. Microbiota Food Health, 31(2): 37–45 (2012)), high water solubility relative to other organogermanium compounds , is the most representative and widely studied and used organogermanium compound, except that it has been used as an anti-inflammatory agent, analgesic (Japanese Patent Publication Sho 62-93293), and heat injury therapeutic agent (Japanese Patent Publication 2002-193802) , immune stimulants, etc., are also used as health supplements, widely added in health care products and cosmetics. Nonetheless, it has never before been used as a primary agent for promoting wound healing.

除了Ge-132以外,其他三氧化二鍺衍生物(germanium sesquioxides)也陸續被研究,有的已被證明具有比Ge-132更佳的誘發干擾素-γ的能力 (Sumi Choi、Changwon Oh、Jeongsoo Han、Jina Park、Jee Hye Choj、Na Young Min、Kwang-Ho Lee、Ae Ja Park、Yeo Jin Kim、Su Jeong Jan, Synthesis and biological evaluation of water-soluble organogermanium,European Journal of Medicinal Chemistry 45 (2010) 1654–1656)。其他的有機者化合物,如雜氮三環鍺化合物(germatranes)、螺旋鍺合物(spiro germanium compounds)、卟啉鍺化合物、二茂鍺化合物等皆已被證明具有免疫與抗腫瘤的活性,而這些藥理活性是源自其誘發產生干擾素-γ的特性 (F. Suzuki、R. R. Brutkiewicz and R.B. Pollard,Br. J. Cancer (1985), 52, 757-763;N. Kakimoto, K. Miyao, M. Akiba, in "Frontiers of Organogermanium, -Tin, Lead Chemistry", E. Lukevics, L. Ignatovich eds., Latvian Institute of Organic Synthesis, 1993;Marcel Gielen Edward R.T. Tiekink,  Metallotherapeutic Drugs And Metal-Based Diagnostic Agents:The Use Of Metals In Medicine, John Wiley & Sons Ltd., 2005)。In addition to Ge-132, other germanium trioxide derivatives (germanium sesquioxides) have also been studied, and some have been shown to have better ability to induce interferon-γ than Ge-132 (Sumi Choi, Changwon Oh, Jeongsoo Han, Jina Park, Jee Hye Choj, Na Young Min, Kwang-Ho Lee, Ae Ja Park, Yeo Jin Kim, Su Jeong Jan, Synthesis and biological evaluation of water-soluble organogermanium, European Journal of Medicinal Chemistry 45 (2010) 1654 –1656). Other organic compounds, such as germana tricyclic germanium compounds (germatranes), spiro germanium compounds, porphyrin germanium compounds, germanocene compounds, etc., have all been proved to have immune and antitumor activities, and These pharmacological activities are derived from their properties that induce the production of interferon-gamma (F. Suzuki, RR Brutkiewicz and RB Pollard, Br. J. Cancer (1985), 52, 757-763; N. Kakimoto, K. Miyao, M. . Akiba, in "Frontiers of Organogermanium, -Tin, Lead Chemistry", E. Lukevics, L. Ignatovich eds., Latvian Institute of Organic Synthesis, 1993; Marcel Gielen Edward RT Tiekink, Metallotherapeutic Drugs And Metal-Based Diagnostic Agents: The Use Of Metals In Medicine, John Wiley & Sons Ltd., 2005).

雖然上述的有機鍺化合物具有誘發干擾素-γ,刺激體內產生轉化生長因子-β1的特性,但至今尚未被用做傷口癒合的主要藥劑,可能之原因是其效果不易顯現,因為經過腸道吸收或體內注射所產生的轉化生長因子不容易到達傷口的表層黏膜,尤其是在一般醫用的低劑量給藥情況下。Although the above-mentioned organogermanium compounds have the properties of inducing interferon-γ and stimulating the production of transforming growth factor-β1 in the body, they have not been used as the main agent for wound healing so far. Or the transforming growth factor produced by in vivo injection cannot easily reach the superficial mucosa of the wound, especially in the case of low-dose administration for general medical purposes.

本發明的藥物使用方法解決了上述問題,使藥物對傷口癒合的促進效果得以充分地展現,方法包括:(一) 直接在傷口部位施用藥物,使藥物在傷口表層處被吸收,並在傷口表層組織中刺激干擾素-γ的產生,也使轉化生長因子-β1在傷口表層中產生,使其促進傷口癒合的效果得以發揮;(二)施用高濃度甚至是純的藥物,以產生足夠的轉化生長因子-β1,使傷口癒合的效果得以顯現;(三) 提高藥物吸收,例如選用液態的藥物,或水溶性較高的固態藥物並保持傷口處適當的濕潤以促進藥物的溶解,以利組織的吸收。The drug use method of the present invention solves the above-mentioned problems, so that the promoting effect of the drug on wound healing can be fully exhibited. Stimulates the production of interferon-γ in the tissue, and also causes the production of transforming growth factor-β1 in the wound surface layer, so that the effect of promoting wound healing can be exerted; (2) The application of high concentrations or even pure drugs to produce sufficient transformation Growth factor-β1, so that the effect of wound healing can be manifested; (3) Improve drug absorption, such as choosing liquid drugs or solid drugs with higher water solubility and keeping the wound properly moist to promote the dissolution of drugs, so as to facilitate the tissue Absorption.

以上本發明的藥物使用方法,使得有機鍺化合物促進傷口癒合的優良效果得以被揭示。因為有機鍺化合物已被證明毒性極低,因此並無造成體內過高藥物劑量之虞。再者,因藥物劑量受制於藥物的吸收速率,因此可以通過調節藥物的溶解(固體藥物)以及施用的藥物總量加以限制。尤其在傷口部位的局部施藥,藥物劑量過高的風險完全可以排除。本發明的藥物除可以單獨包括有機鍺化合物外,也可以進一步包括其他的輔助劑、添加物;藥物的型態可以是粉劑、膏劑、乳劑或液劑。使用膏劑、乳劑或液劑時則可直接塗抹;使用粉劑時,可將藥劑定量散撒在傷口,再於傷口噴灑水霧使藥劑濕潤,以便於塗抹均勻,並幫助藥劑溶解,以利組織吸收。The above medicine using method of the present invention enables the excellent effect of organogermanium compound to promote wound healing to be revealed. Because organogermanium compounds have been shown to be extremely low-toxic, there is no risk of causing excessive drug doses in the body. Furthermore, since the drug dose is subject to the rate of absorption of the drug, it can be limited by adjusting the dissolution of the drug (solid drug) and the total amount of drug administered. Especially for topical application at the wound site, the risk of excessive drug doses can be completely ruled out. In addition to the organic germanium compound alone, the medicament of the present invention can also further include other adjuvants and additives; the form of the medicament can be powder, ointment, emulsion or liquid. When using ointment, emulsion or liquid, you can apply it directly; when using powder, you can scatter the medicine quantitatively on the wound, and then spray water mist on the wound to moisten the medicine, so as to spread the medicine evenly, and help the medicine dissolve for tissue absorption. .

經採取以上的藥物以及使用方法,進行皮膚傷口癒合的實驗(於實施例詳述),觀察到本發明以下的效果:(一) 傷口的癒合速率十分快速,比施用市售傷口癒合藥膏明顯快速很多;(二) 在未施用消毒藥劑的情況下,傷口在癒合過程中沒有發炎現象;(三) 傷口的滲出液大幅降低,且施用高濃度藥劑能有效抑制滲出液產生;(四) 沒有結痂現象,傷口癒合後皮膚呈現平滑的外觀。After taking the above medicine and method of use, carry out the experiment of skin wound healing (detailed in the embodiment), observe the following effects of the present invention: (1) the healing rate of the wound is very fast, obviously faster than applying commercially available wound healing ointment (2) In the absence of antiseptics, the wound did not become inflamed during the healing process; (3) The exudate of the wound was greatly reduced, and the application of high concentrations of the drug could effectively inhibit the production of exudate; (4) There was no contamination. The scab phenomenon, the smooth appearance of the skin after the wound has healed.

本發明藥物的使用方式除了以上用外敷方式促進體外傷口的癒合外,也不排除在限制劑量下採用口服或注射方式用於體內潰瘍傷口癒合的促進。本發明進一步提供以所述藥物為主要成分而型態為粉劑、膏劑、乳劑或液劑的內用或外用藥劑。In addition to promoting the healing of external wounds by external application, the use of the medicament of the present invention does not exclude the use of oral or injection methods for promoting the healing of ulcers and wounds in vivo under limited doses. The present invention further provides an internal or external medicament with the medicament as the main component and in the form of powder, ointment, emulsion or liquid.

實施例: 以下本發明的實施例是為了示範本發明的效果,不能作為對本發明申請專利範圍的限制。Examples: The following examples of the present invention are intended to demonstrate the effects of the present invention, and cannot be used as a limitation on the scope of the patent application of the present invention.

(1) 試驗藥劑 傷口癒合試驗是以雙-羧乙基鍺倍半氧化物(Ge-132)進行,是購自市販的純Ge-132細粉,並先用100 mesh的篩網過篩後使用。為了比較起見,試驗採用以下三種組合進行,並以生理食鹽水作為傷口清洗劑,其中A劑為不含其他添加物的純Ge-132粉末;B劑為混合粉末,含5 wt% Ge-132,其餘95 wt%為醫藥級ZnO (純度 > 99.9%);C劑為市售之銀胺劑乳膏,每克乳膏含10毫克磺胺嘧啶銀 (siliver sulfadazine);D劑為醫用凡士林,當作對照組。(1) Test drug The wound healing test was performed with bis-carboxyethylgermanium sesquioxide (Ge-132), which was a pure Ge-132 fine powder purchased from the market, and was first sieved with a 100-mesh sieve before use. For comparison, the experiment was carried out with the following three combinations, and normal saline was used as the wound cleaning agent, wherein agent A was pure Ge-132 powder without other additives; agent B was mixed powder containing 5 wt% Ge-132 132, the remaining 95 wt% are pharmaceutical grade ZnO (purity > 99.9%); agent C is a commercially available silver amine cream, each gram of cream contains 10 mg of silver sulfadiazine (silver sulfadazine); agent D is medical vaseline , as the control group.

(2) 試驗用動物 試驗之動物為出生95天的紐西蘭白兔兩隻,分別重2.35公斤與2.42公斤。實驗前先將兔子注射Acetylpromazine (3 mg/kg)進行麻醉,然後再以Octocaine®50進行浸潤。然後在兔子後背中間區域除毛,完成後用預熱500℃之1 cm x 1.5 cm之長方形烙鐵,在除毛區域的脊椎兩側,每側各選擇二處,分別接觸三秒鐘,造成四個燒燙傷口。(2) Experimental animals The test animals were two New Zealand white rabbits born at 95 days, weighing 2.35 kg and 2.42 kg respectively. The rabbits were anesthetized by injection of Acetylpromazine (3 mg/kg) before the experiment, and then infiltrated with Octocaine®50. Then remove the hair in the middle area of the rabbit's back. After completion, use a rectangular soldering iron of 1 cm x 1.5 cm preheated to 500°C. Select two spots on each side of the spine in the hair removal area, and touch them for three seconds respectively, causing four A burning wound.

(3) 試驗方法 於兔子的燒焦表皮以生理食鹽水清洗後,再以醫用棉球擦拭,然後施用試驗藥劑。其中A劑和B劑為粉劑,先秤取預定使用的粉劑(重量以每cm2 傷口使用0.01克粉劑計算),然後將粉劑分散撒在傷口範圍內,再以噴霧瓶向傷口噴水霧,使粉劑適度濕潤,最後再以玻璃塗抹棒將濕潤的粉劑塗抹均勻;C劑為藥膏,依照出品廠商的用藥指示塗抹在傷口;D劑為凡士林,塗抹覆蓋傷口作為對照組。施藥期間每天施藥1次。施藥前,先將傷口以生理食鹽水清洗,並以醫用棉球擦拭後再照相,以量測傷口大小及觀察變化情況,然後再進行施藥,施藥後以醫用紗布遮蓋傷口。傷口大小是照相後使用PHOTOSHOP軟體之面積量測功能進行量測。(3) Test method The burnt epidermis of the rabbit was washed with physiological saline, then wiped with a medical cotton ball, and then the test agent was applied. Wherein agent A and agent B are powders, first weigh the powder to be used (the weight is calculated by using 0.01 g of powder per cm 2 wound), then disperse the powder in the wound area, and then spray water mist to the wound with a spray bottle to make The powder is moderately moistened, and finally the moistened powder is spread evenly with a glass applicator; Agent C is ointment, applied to the wound according to the manufacturer's instructions; Agent D is Vaseline, smeared to cover the wound as a control group. Apply once a day during the application period. Before applying the medicine, first wash the wound with physiological saline, wipe it with a medical cotton ball, and then take a picture to measure the size of the wound and observe the change. The size of the wound is measured using the area measurement function of the PHOTOSHOP software after taking a photo.

(4) 試驗結果 試驗結果包含:1) 傷口外觀變化;2) 傷口大小變化與比較。(4) Test results The test results include: 1) changes in wound appearance; 2) changes and comparisons in wound size.

1) 傷口外觀變化之觀察 本試驗以兩隻兔子進行兩組條件重復的試驗,兔子燒傷部位之表皮呈現焦黑的咖啡色,施藥結果顯示兩組試驗的外觀變化差異不大。分別說明兩組結果如下:1) Observation of changes in wound appearance In this experiment, two rabbits were used to carry out two sets of repeated experiments. The skin of the rabbit's burn area was charred brown, and the results showed that there was little difference in appearance between the two groups of experiments. The two sets of results are described as follows:

第一組試驗結果: A劑處理之傷口:初期時燒焦表皮外觀無明顯變化;第14天,燒焦之表皮一次性完全脫離,傷口面積僅剩中間區域,面積為原傷口的9.56%,癒合部分之新表皮表面平滑(請參圖2A),沒有發炎與結痂現象;施藥至第20天,傷口完全癒合(請參圖3A)。傷口癒合的過程沒有發炎現象,僅在最後癒合的中間部分出現極輕微幾乎可以忽視的疤痕,皮毛也隨之逐漸長出; B劑處理之傷口:在第14天時(即A劑處理時燒焦表皮完全脫離之時點),燒焦表皮之周圍部分脫離,經剪除周圍已脫離之燒焦表皮後,中間區域38.62%的面積尚未癒合(請參圖2B);施藥至第20天時(即A劑處理時傷口完全癒合之時點), 傷口縮小為6.12%的面積(請參圖3B);第25天時,傷口完全癒合。傷口癒合的過程沒有發炎現象,但有輕度的結痂現象,傷口癒合之後表皮平滑度較施用A劑者差; C劑處理之傷口:第14天時(即A劑處理時燒焦表皮完全脫離之時點),燒焦之表皮周圍部份脫離,傷口面積則擴大為原傷口的132.83%(請參圖2C);第20天時(即A劑處理時傷口完全癒合之時點),燒焦表皮始完全脫離,尚未癒合之傷口為原傷口面積的98.45%(請參圖3C);第43天時,傷口完全癒合。傷口癒合的過程有明顯發炎現象,施藥期間傷口面積一度擴大,結痂的現象遠比施用B劑者明顯,燒焦部位癒合後之表皮平滑度也較施用B劑者差; D劑處理之對照傷口:在第14天時(即A劑處理時燒焦表皮完全脫離之時點),傷口周圍部分之燒焦表皮有部分脫離,經剪除周圍部分脫離之表皮後,中間區域65.84%的面積尚未癒合(請參圖2D);第18天時,燒焦表皮始完全脫離;第20天時(即A劑處理時傷口完全癒合之時點),傷口縮小為原面積的7.62%(請參圖3D);第36天時,傷口完全癒合。傷口癒合的過程有輕微的發炎現象,結痂現象比施用B劑明顯,燒焦部位癒合後之表皮平滑度比施用B劑者差,但比施用C劑者佳。The first set of test results: Wounds treated with agent A: There was no obvious change in the appearance of the scorched epidermis at the initial stage; on the 14th day, the scorched epidermis was completely detached at one time, leaving only the middle area of the wound, which was 9.56% of the original wound, and the surface of the new epidermis of the healed part It was smooth (see Figure 2A), without inflammation and scabbing; the wound was completely healed on the 20th day of application (see Figure 3A). There is no inflammation in the process of wound healing, only a very slight and almost negligible scar appears in the middle part of the final healing, and the fur gradually grows; Wounds treated with agent B: On the 14th day (that is, the point when the scorched epidermis was completely detached when treated with agent A), the surrounding part of the scorched epidermis was detached. The area has not healed yet (see Figure 2B); on the 20th day (that is, when the wound was completely healed when agent A was treated), the area of the wound was reduced to 6.12% (see Figure 3B); on the 25th day, the wound was fully healed. There is no inflammation in the process of wound healing, but there is mild scabbing, and the smoothness of the epidermis after the wound is healed is worse than that of the agent A; The wound treated with agent C: On the 14th day (that is, the point when the scorched epidermis was completely detached during the treatment with agent A), the surrounding part of the scorched epidermis was detached, and the wound area expanded to 132.83% of the original wound (please refer to Figure 2C) ; On the 20th day (that is, when the wound was completely healed when the agent A was treated), the scorched epidermis was completely detached, and the unhealed wound was 98.45% of the original wound area (please refer to Figure 3C); on the 43rd day, the wound was completely heal. There is obvious inflammation in the process of wound healing. During the application, the wound area once expanded, and the phenomenon of scabbing is far more obvious than that of the B agent. Control wound treated with agent D: on the 14th day (that is, the point when the scorched epidermis was completely detached during agent A treatment), the scorched epidermis in the surrounding part of the wound was partially detached. % of the area has not healed (please refer to Figure 2D); on the 18th day, the scorched epidermis was completely detached; on the 20th day (that is, when the wound was completely healed when the agent A was treated), the wound was reduced to 7.62% of the original area ( See Figure 3D); on day 36, the wound was completely healed. In the process of wound healing, there is slight inflammation, and the scab phenomenon is more obvious than that of the B agent.

第二組試驗結果 第二組的試驗結果顯示,燒焦表皮完全脫離之天數與傷口完全癒合之天數雖與第一組差異甚小,各藥劑在發炎情況、結痂情況與癒合後表皮平滑度等的表現,優劣次序與第一組相同。兩組實驗之結果詳如表一。 表一:傷口外觀變化觀察 組別 傷口特性觀察 施用藥劑 A劑 B劑 C劑 D劑 第 一 組 燒焦表皮完全脫離之天數 14 18 20 18 傷口完全癒合之天數 20 25 43 36 發炎情況 X 結痂情況 X 癒合後表皮平滑度 X 第 二 組 燒焦表皮完全脫離之天數 13 17 22 18 傷口完全癒合之天數 19 23 48 38 發炎情況 X 結痂情況 X 癒合後表皮平滑度 X 註:◎優良;○良;△普通;X不良。The test results of the second group The test results of the second group showed that although the days for the burnt epidermis to be completely detached and the days for the wound to heal completely were little different from those of the first group, the inflammation, scab and the smoothness of the healed epidermis of each agent were significantly different. and so on, the order of pros and cons is the same as that of the first group. The results of the two groups of experiments are shown in Table 1. Table 1: Observation of changes in wound appearance group Observation of wound characteristics administer the drug Agent A Agent B Agent C Agent D First group Number of days until the burnt epidermis is completely detached 14 18 20 18 Days to complete wound healing 20 25 43 36 Inflammation X scab X Epidermal smoothness after healing X Second Group Number of days until the burnt epidermis is completely detached 13 17 twenty two 18 Days to complete wound healing 19 twenty three 48 38 Inflammation X scab X Epidermal smoothness after healing X Note: ◎excellent; ○good; △fair; X poor.

2) 傷口大小變化 傷口大小的比較是以A劑處理時燒焦表皮完全脫離以及傷口完全癒合之時點為取樣日,並以取樣傷口與原傷口進行大小比較,以百分比(%)表示之,結果如表二所示。 表二:傷口大小變化比較 組 別 施藥天數 對照於原傷口大小之比例(%) A劑 B劑 C劑 D劑 第一組 0 100 100 100 100 14 9.56 38.62 132.83 68.54 20 0 6.12 98.45 7.62 第二組 0 100 100 100 100 13 8.92 39.03 146.60 71.37 19 0 6.56 115.75 9.03 2) Changes in wound size The comparison of wound size is based on the time point when the burnt epidermis is completely detached and the wound is completely healed when the agent A is treated as the sampling day, and the size of the sampled wound is compared with the original wound, expressed as a percentage (%), the result As shown in Table 2. Table 2: Comparison of changes in wound size group Application days The ratio of control to original wound size (%) Agent A Agent B Agent C Agent D First group 0 100 100 100 100 14 9.56 38.62 132.83 68.54 20 0 6.12 98.45 7.62 Second Group 0 100 100 100 100 13 8.92 39.03 146.60 71.37 19 0 6.56 115.75 9.03

表二的試驗結果顯示,第一組中施用A劑者,在第14天時燒焦的表皮完全脫離,傷口面積縮小為原傷口面積的9.56%(請參圖2A),此時施用其他藥劑的各傷口對照於原傷口之比例為:B劑為原傷口面積的38.62%(請參圖2B)、C劑為132.83%(請參圖2C), D劑 (對照組)為68.54%(請參圖2D)。第二組的實驗結果呈現與第一組類似的癒合情況,其中A劑組在第13天時燒焦表皮完全脫離,第19天時傷口完全癒合,同樣時點的B劑、C劑、D劑等之未癒合傷口與原傷口之面積比也如表二所記載,與第一組的變化情況接近。The test results in Table 2 show that the scorched epidermis completely detached from the scorched epidermis on the 14th day in the first group administered agent A, and the wound area was reduced to 9.56% of the original wound area (please refer to Figure 2A), and other agents were administered at this time The ratio of each wound control to the original wound is: agent B is 38.62% of the original wound area (please refer to Figure 2B), agent C is 132.83% (please refer to Figure 2C), agent D (control group) is 68.54% (please refer to Figure 2C) See Figure 2D). The experimental results of the second group showed a similar healing situation to the first group. The burnt epidermis was completely detached in the A group on the 13th day, and the wound was completely healed on the 19th day. At the same time point, the B, C and D agents The area ratio of the unhealed wound to the original wound is also recorded in Table 2, which is close to the changes in the first group.

以上實驗結果顯示,施用包括雙-羧乙基鍺倍半氧化物的有機鍺化合物的藥物時,不論A劑或B劑對傷口癒合皆有顯著的促進效果,也有抑制發炎、結痂輕微、在癒合的過程傷口幾乎無滲出液(exudate)產生且保持乾淨,以及癒合後表面平滑且無疤痕等現象,其中A劑的效果明顯優於B劑,顯示藥物濃度愈高對傷口癒合的促進效果愈佳。本實驗亦證實以有機鍺化合物為單一藥物即可同時發揮傷口消毒、消炎、滅菌以及抑制滲出液產生等效果,惟可理解的是,這不意謂需要排除其他藥物或添加物如抗生素、止痛劑、麻醉劑、維生素等的共用。The above experimental results show that when the drug containing the organogermanium compound of bis-carboxyethylgermanium sesquioxide is administered, either agent A or agent B has a significant promoting effect on wound healing, and also inhibits inflammation, mild scabbing, and During the healing process, the wound has almost no exudate (exudate) and is kept clean, and the surface is smooth and scar-free after healing. The effect of agent A is significantly better than that of agent B, showing that the higher the drug concentration, the better the effect of promoting wound healing. good. This experiment also confirms that using organic germanium compound as a single drug can simultaneously exert the effects of wound disinfection, anti-inflammatory, sterilization and inhibition of exudate production, but understandably, this does not mean that other drugs or additives such as antibiotics and analgesics need to be excluded. , anesthetics, vitamins, etc.

本發明還提供一種促進傷口癒合及/或治療傷口的方法,包括使用前述之藥物。使用方法包括以外敷、口服、注射等方式投予患者前述之藥物。藥物還可以例如粉劑或其水漿、膏劑、乳劑等型態用於外敷,以溶液、粉末懸浮液等型態用於口服或注射,然不以此為限。The present invention also provides a method for promoting wound healing and/or treating wounds, comprising using the aforementioned medicament. The methods of use include external application, oral administration, injection, etc. to administer the aforementioned drugs to patients. The drug can also be used for external application in the form of powder or its water slurry, ointment, emulsion, etc., and oral or injection in the form of solution, powder suspension, etc., but it is not limited to this.

雖然本發明已以實施例揭露如上,然其並非用以限定本發明,本發明所屬技術領域中具有通常知識者,在不脫離本發明之精神和範圍內,當可作些許之更動與潤飾,因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。Although the present invention has been disclosed as above with examples, it is not intended to limit the present invention. Those with ordinary knowledge in the technical field to which the present invention pertains can make some changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention should be determined by the scope of the appended patent application.

without

圖1:施藥後第7天之傷口情況。 圖2:施藥後第14天之傷口情況。 圖3:施藥後第20天之傷口情況。Figure 1: Wound condition on day 7 after application. Figure 2: Wound condition on day 14 after application. Figure 3: Wound condition on day 20 after application.

Claims (18)

一種促進傷口癒合的藥物,其包括能刺激體內產生干擾素的一有機鍺化合物為主要成分。A medicine for promoting wound healing, which comprises an organic germanium compound which can stimulate the production of interferon in the body as the main component. 如請求項1所述之促進傷口癒合的藥物,其中該有機鍺化合物選自以下之至少一種:雙-羧烷基鍺倍半氧化物(bis-carboxyalkyl germanium sesquioxide)、雙-羧烷基鍺倍半氧化物之衍生物、鍺烷化合物(germanes)、雜氮三環鍺化合物(germatranes)、螺旋鍺化合物(spirogermanium compounds)、鍺卟啉化合物(germanium porphyrines)以及二茂鍺化合物(germanocenes)。The medicine for promoting wound healing according to claim 1, wherein the organic germanium compound is selected from at least one of the following: bis-carboxyalkyl germanium sesquioxide, bis-carboxyalkyl germanium sesquioxide, bis-carboxyalkyl germanium sesquioxide Derivatives of semi-oxides, germanes, germana tricyclic germanium compounds (germatranes), spirogermanium compounds, germanium porphyrines and germanocenes. 如請求項2所述之促進傷口癒合的藥物,其中該雙-羧烷基鍺倍半氧化物之分子代表式為:
Figure 03_image001
式中之R1、R2、R3為以下反應基:H、取代或未取代的低碳烷基(alkyl)如甲基(methyl)或乙基(ethyl)、芳基(aryl)、雜芳基(hetaryl)、取代或未取代的胺基(amino group)或醯胺基(amido group)之一; X為羥基(OH)、O-Na、O-K、鹼性胺基(basic amino group)、芳基(aryl)或雜芳基(hetaryl)之一。
The medicine for promoting wound healing as claimed in claim 2, wherein the molecular formula of the bis-carboxyalkyl germanium sesquioxide is:
Figure 03_image001
R1, R2, R3 in the formula are the following reactive groups: H, substituted or unsubstituted lower alkyl (alkyl) such as methyl (methyl) or ethyl (ethyl), aryl (aryl), heteroaryl ( hetaryl), substituted or unsubstituted amino group (amino group) or one of amido group (amido group); X is hydroxyl (OH), O-Na, OK, basic amino group (basic amino group), aryl group (aryl) or one of heteroaryl (hetaryl).
如請求項2所述之促進傷口癒合的藥物,其中該雙-羧烷基鍺倍半氧化物為雙-羧乙基鍺倍半氧化物(Ge-132)。The medicine for promoting wound healing according to claim 2, wherein the bis-carboxyalkylgermanium sesquioxide is bis-carboxyethylgermanium sesquioxide (Ge-132). 如請求項2所述之促進傷口癒合的藥物,其中該鍺烷化合物之分子代表式為:
Figure 03_image002
式中之R1、R2、R3為H、取代或未取代的低碳烷基(alkyl)如甲基(methyl)或乙基(ethyl)之一;R4為烷基;X為取代或未取代的醣苷基(glycosyl group)之一。
The medicine for promoting wound healing as claimed in claim 2, wherein the molecular formula of the germane compound is:
Figure 03_image002
R1, R2 and R3 in the formula are one of H, substituted or unsubstituted lower alkyl such as methyl or ethyl; R4 is alkyl; X is substituted or unsubstituted One of the glycosyl groups.
如請求項5所述之促進傷口癒合的藥物,其中該鍺烷化合物為6-O-3-三甲基鍺烷-丙基-β-D-吡喃葡萄醣苷(6-O-[3-(tri-methylgermyI)propyl]-β-D-glucopyranoside (GeOH))。The medicine for promoting wound healing according to claim 5, wherein the germane compound is 6-O-3-trimethylgermane-propyl-β-D-glucopyranoside (6-O-[3- (tri-methylgermyI)propyl]-β-D-glucopyranoside (GeOH)). 如請求項2所述之促進傷口癒合的藥物,其中該雜氮三環鍺化合物(germatranes)之分子代表式為:
Figure 03_image004
式中之R為苯基(benzyl group)、苯溴基(bromobenzyl group)、肉桂酸基[-CH(C6 H4 OH)CH2 COOH]、咖啡酸基[-CH(C6 H3 (OH)2 )CH2 COOH]之一。
The medicine for promoting wound healing according to claim 2, wherein the molecular formula of the aza-tricyclic germanium compound (germatranes) is:
Figure 03_image004
R in the formula is phenyl group (benzyl group), phenyl bromide group (bromobenzyl group), cinnamic acid group [-CH(C 6 H 4 OH)CH 2 COOH], caffeic acid group [-CH(C 6 H 3 ( One of OH) 2 )CH 2 COOH].
如請求項2所述之促進傷口癒合的藥藥,其中該螺旋鍺化合物為3-(2, 8,9-trioxa-aza-1-germatricyclo-[3,3,3,0]-undecane-1-yl)caffeic Acid、4,4-dialkyl-4-germa-cyclohexano 或 8,8-dialkyl-8-germaazaspiro(4,5)decan。The medicine for promoting wound healing according to claim 2, wherein the spiro germanium compound is 3-(2,8,9-trioxa-aza-1-germatricyclo-[3,3,3,0]-undecane-1 -yl)caffeic Acid, 4,4-dialkyl-4-germa-cyclohexano or 8,8-dialkyl-8-germaazaspiro(4,5)decan. 如請求項2所述之促進傷口癒合的藥物,其中該二茂鍺化合物為十苯基二茂鍺化合物(decaphenylgermanocenes)。The medicine for promoting wound healing according to claim 2, wherein the germanocene compound is decaphenylgermanocenes. 如請求項2所述之促進傷口癒合的藥物,其中該鍺卟啉化合物(germanium porphyrines)為二烷基-5,10,15,20-四-[30,50二(三級丁基)苯基]卟啉鍺(dialkyl-5,10,15,20-tetra-[30,50-bis-(t-butyl)phenyl]-porphynatogermanium)。The medicine for promoting wound healing according to claim 2, wherein the germanium porphyrines is dialkyl-5,10,15,20-tetra-[30,50bis(tertiary butyl)benzene base] porphyrin germanium (dialkyl-5,10,15,20-tetra-[30,50-bis-(t-butyl)phenyl]-porphynatogermanium). 如請求項1所述之促進傷口癒合的藥物,其為以下型態之一:溶液、粉末懸浮液、乳劑、膏劑以及粉劑。The medicine for promoting wound healing according to claim 1, which is in one of the following forms: solution, powder suspension, emulsion, ointment and powder. 如請求項1所述之促進傷口癒合的藥物,其中該有機鍺化合物的濃度為0.3 wt%以上。The medicine for promoting wound healing according to claim 1, wherein the concentration of the organic germanium compound is 0.3 wt% or more. 如請求項12所述之促進傷口癒合的藥物,其中該有機鍺化合物的濃度為1 wt%以上。The medicine for promoting wound healing according to claim 12, wherein the concentration of the organic germanium compound is 1 wt% or more. 如請求項13所述之促進傷口癒合的藥物,其中該有機鍺化合物的濃度為2 wt%以上。The medicine for promoting wound healing according to claim 13, wherein the concentration of the organic germanium compound is 2 wt% or more. 如請求項1所述之促進傷口癒合的藥物,更包括以下至少一種之添加物:滅菌劑、抗生素、潤濕劑、維生素、添充劑以及其他皮膚傷口癒合劑。The medicine for promoting wound healing as described in claim 1 further includes at least one of the following additives: sterilant, antibiotic, wetting agent, vitamin, supplement and other skin wound healing agent. 如請求項1所述之促進傷口癒合的藥物,其使用至少為以下方式之一:外敷、口服以及注射。The medicine for promoting wound healing as claimed in claim 1, which is used in at least one of the following ways: external application, oral administration and injection. 一種如請求項1~16任一項所述之促進傷口癒合的藥物在製備一治療傷口之藥劑的用途,其中該治療傷口之藥劑的投予方式選自外敷、口服以及注射。A use of the medicament for promoting wound healing according to any one of claims 1 to 16 in preparing a medicament for treating wounds, wherein the administration mode of the medicament for treating wounds is selected from external application, oral administration and injection. 如請求項1~15任一項所述之促進傷口癒合的藥物,其以粉劑投予時,係將粉劑直接塗抹在傷口,並適時噴水霧使傷口保持適度濕潤。When the medicine for promoting wound healing according to any one of claims 1 to 15, when it is administered as powder, the powder is directly applied to the wound, and water mist is sprayed at appropriate time to keep the wound moderately moist.
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