The medicine is formulated from organic germanium compounds and glucosamine compounds.

Abstract

The invention relates to a drug composed of an organic germanium compound and a glucosamine compound characterized by: (1) that the drug is a highly water-soluble salt composed of an organic germanium compound and a glucosamine compound suitable for the formulation of various beneficial pharmaceutical formulations; and (2) that the drug containing this salt retains the biochemical properties, pharmacological properties and medicinal efficacy of its constituent components. In addition, due to the pharmacological properties of its components being medically complementary, the drug is of superior efficacy in many medical applications, including but not limited to promoting wound healing.

Description

Medicine prepared from organic germanium compound and glucosamine compound and use thereof Technical Field

[0001] The present invention relates to a drug prepared from an organic germanium compound and a glucosamine compound and its use, and in particular to a drug having analgesic, anti-inflammatory, antioxidant, anti-hypoxia, immunomodulatory, antiviral, antibacterial, coagulation, cell proliferation acceleration and other effects, which can stimulate an organism to secrete interferon and derive transforming growth factor, as well as its medical applications including but not limited to promoting the healing of various wounds. Background Art

[0002] Research on the biochemical activity and medical application of organogermanium compounds has a history of several decades, and some of them have been found to have analgesic, anti-inflammatory, antioxidant, antihyproxic, immunomodulating, and antiviral effects (VG Lakhtin et al., "Synthesis and application of organogermanium compounds", Polymer Science Series D, Vol. 4, Iss. 3, pp 221-227, 2011-07-01; DW Niesel, CB Hess, YJ Cho, KD Klimpel and GR Klimpel, Infection and Immunity, June 1986, Vol. 52, No. 3, pp 828-833; LG Menchikov and MA Ignatenko, "Biological Activity of Organogermanium Compounds-A Review", Pharmaceutical Journal of Medicine, 1996, 46(2): 115-116). Chemistry Journal, Vol. 46, No. 11, February, 2013), among which bis(2-carboxyethylgermanium) sesquioxide (Ge-132) and its derivatives are the most widely and deeply studied among organogermanium sesquioxides.Bis-carboxyethylgermanium sesquioxide (Ge-132) and its derivatives have been widely studied and applied in anti-cancer, anti-hypertension, liver disease prevention, anti-rheumatic (Pronai, L. and Arimori, S., "Decreased Plasma Superoxide Scavenging Activity in Immunological Disorder—Carboxyethylgermanium sesquioxide (Ge-132) as a Promoter of Prednisolone", Biotherapy, 1992, 4, 1-8), anti-cataract (Unaka, N.J. et al., 1995, "Effect of Germanium-132 on Galactose Cataracts and Glycation in Rats", Experimental Eye Research, 61, 155-164), osteoporosis inhibition, and inflammation treatment. They are also used in the manufacture of cosmetics and nutritional supplements. Although recent research (Robin A. Reddeman et al., "A Toxicological Evaluation of Germanium Sesquioxide (Organic Germanium)", Hindawi, Journal of Toxicology, Vol. 2020, Article ID 6275625, 17 pages) has determined the No Observable Adverse Effect Level (NOAEL) of Ge-132 to be 2000 mg / kg body weight / day, making it a very low-toxic substance, it can be contaminated with germanium dioxide (GeO2), leading to severe nephrotoxicity. Therefore, avoiding this contamination has become a key issue in the preparation of organic germanium pharmaceuticals. Preparing organic germanium in liquid form is an effective method to avoid contamination with solid germanium dioxide and the limitations of its application due to its low water solubility, which is also one of the objectives of the present invention.

[0003] In addition to organogermanium sesquioxides and their derivatives, other types of organogermanium compounds, including germanes, germatranes, spirogermanium compounds, germanium porphyrines, and germanocenes, have also been shown to exhibit biological activities similar to those of bis-carboxyethylgermanium sesquioxide (LG Menchikov and MA Ignatenko, “MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION: Biological Activity of Organogermanium Compounds (A Review)”, Pharmaceutical Chemistry Journal, Vol. 46, No. 11, February 2013).

[0004] Numerous studies have also demonstrated that organic germanium compounds can stimulate the secretion of interferon-γ and derive transforming growth factor (TGF) in the body, suggesting an effective approach for promoting wound healing. Wounds are caused by many factors. In addition to skin wounds such as trauma, lacerations, abrasions, knife wounds, burns, scalds, sunburn, acne, diabetic ulcers, and bedsores caused by prolonged bed rest, internal ulcers are also common. Wound healing is a complex and slow process. New epithelial and connective tissues are formed through the migration and proliferation of cells during wound healing. Therefore, promoting cell migration, differentiation, and proliferation can aid wound healing. Previous studies (Paul Martin, "Wound Healing - Aiming for Perfect Skin Regeneration", pp. 75-81, SCIENCE, Vol. 276, April 4, 1997) have shown that the so-called "epidermal growth factor family," including epidermal growth factor (EGF), transforming growth factor-α (TGF-α), and heparin-binding epidermal growth factor (HB-EGF), are released in large quantities at the site of epidermal injury. These factors play a key role in regulating keratinocyte formation and cell proliferation at the wound edge. Furthermore, studies have also found that exogenous EGF and TGF-α applied to burns on pig backs enhance epidermal cell regeneration (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 can act as cell migration factors (motogens) and cell division factors (mitogens) to drive wound closure (Y. Barrandon and H. Green, Cell 50, 1131 (1987)).

[0005] Previous in vitro studies on the effects of various cytokines and peptide growth factors on intestinal epithelial cell recovery have shown that four factors, namely transforming growth factor-α, epidermal growth factor, interleukin-1β (IL-1β) and interferon-γ (IFN-γ), promoted the production of biologically active TGF-β1 peptide on injured IEC-6 intestinal monolayer membranes and enhanced the recovery of intestinal epithelial cell wounds by 2.3 to 5.5 times (Diagnass, AU, Podolsky, DK, Gastroenterology, 105(5), 1323-1332 (1993)).

[0006] In the prior art, some wound healing agents use growth factors as their primary ingredients. However, the use of exogenous growth factors for wound treatment has the following disadvantages: (1) Growth factors are unstable proteins that easily degrade during storage. When administered orally, they are digested and destroyed before entering the bloodstream; (2) Growth factors are slowly absorbed by the body and rapidly degraded, resulting in limited effectiveness of topical growth factor ointments; and (3) Many growth factors are species-specific. If administered parenterally, they may be recognized as foreign and rejected, triggering a dangerous immune response. For these reasons, exogenous growth factors are not ideal wound healing agents. Other literature indicates that there is no evidence that exogenous growth factors administered parenterally reach the skin, connective tissue, and supporting tissues. Therefore, endogenous growth factors are truly effective in promoting wound healing. The preparation of drugs that produce endogenous growth factors is the primary objective of the present invention.

[0007] H. Matsumoto et al. tested the wound healing effect of an isotonic solution containing 1.8% Ge-132 on rats (H. Matsumoto at al., “Restorative effect of organic germanium compound (Ge-132) on dermal injury”, Wound Medicine 15, 6–10 (2016)). The results showed that the wound-shrinking effect of the isotonic solution was not significantly different from that of saline. The experimental results are shown in Comparative Example 1, Figure 1. While the solution showed wound-shrinking effect, it was not significantly different from the saline control group and was significantly inferior to the effect of the present invention. One of the objectives of the present invention is to develop a wound-healing drug that has a higher wound-healing effect and can inhibit exudate production.

[0008] Another ingredient for preparing the drug of the present invention is a glucosamine compound containing an active amine group, including glucosamine monosaccharides, disaccharides, polysaccharides of various polymerization degrees (such as chitosan oligosaccharides, chitosan), and derivatives thereof. Glucosamine is a compound in which one of the hydroxyl groups in glucose is replaced by an amine group and is a natural amino monosaccharide. A large amount of the glucosamine derivative N-acetylglucosamine is present in the chitin in the shells of arthropods such as shrimp and crabs. Therefore, by deacetylation of the chitin in the shells of shrimp and crabs, polyglucosamine, commonly known as chitosan or chitosan (chito-NH2), can be obtained. Its molecular structure is shown in Formula (I):

[0009] Formula (I): Chemical structure of chitosan

[0010] Generally, commercially available chitosan is not completely deacetylated. Therefore, as shown in formula (I), it has different contents of N-acetamide groups due to differences in the degree of deacetylation.

[0011] Chitosan is a polysaccharide that can be further depolymerized and subsequently deacetylated by methods such as chemical hydrolysis, enzymatic degradation, or high-energy impact, yielding oligosaccharides with a lower degree of polymerization (DP) and a higher degree of deacetylation, known as chitooligosaccharides (COS-NH2). Aside from their lower DP and higher DP, chitooligosaccharides share a similar chemical structure to chitosan. For clarity, some literature defines chitosan as polyglucosamines with a DP ≤ 20 and an average molecular weight ≤ 3900 Daltons (Da) (VK Mourya, NN Inamdar, and YM Choudhari, "Chitooligosaccharides: Synthesis, Characterization and Applications," Polymer Science, Ser. A, 2011, Vol. 53, No. 7, pp. 583–612).

[0012] Glucosamine monosaccharide can also be obtained by further depolymerization of chitosan or chitosan oligosaccharides, which is also the main method for preparing glucosamine monosaccharide. Among them, the enzymatic depolymerization method is favored due to its mild reaction conditions, high yield and specificity, and the fact that it does not change the structure of glucosamine (Pan et al., "Preparation of glucosamine by hydrolysis of chitosan with commercial α-amylase and glucoamylase", J. Zhejiang Univ-Sci B (Biomed & Biotechnol) 2011, 12(11):931-934). Glucosamine monosaccharide has a molecular weight of 179.17 and a degree of polymerization of 1. In the preparation and application of the drug of the present invention, it has similar properties to chitosan oligosaccharides.

[0013] Chitosan is a bioabsorbable polymer that has found widespread application in various industries, including food, materials, healthcare, agriculture, and environmental protection. Due to its excellent biocompatibility and non-toxicity, chitosan is used as a gene delivery vector for gene therapy. Its superior adhesion properties facilitate the transport of various drugs across cell membranes, leading to its use in controlled-release drug delivery systems for the treatment of various diseases, including cancer. Furthermore, due to its physiological functions, such as antibacterial, blood coagulation, cell proliferation acceleration, skin tissue repair, tissue adhesion prevention, scar inhibition, and joint cartilage protection, it is also used in hemostasis and wound healing.

[0014] Chitosan is insoluble in water, but its application, whether as a hydrosol, hydrogel, solid particle, film, or fiber, must be achieved through dissolution. Therefore, developing a method for preparing chitosan solutions that is simple, fast, requires no external solvents, and avoids contamination by toxic components has long been a challenge for its medical applications. Addressing this issue is the purpose of the present invention.

[0015] Unlike chitosan, chitosan oligosaccharides have a higher degree of deacetylation, a lower degree of polymerization, a lower molecular weight, and a higher viscosity. They are also highly water-soluble and possess more significant pharmacological properties, such as antibacterial, antioxidant, anti-inflammatory, antihypertensive, and drug / DNA delivery properties. Furthermore, chitosan oligosaccharides have demonstrated anti-diabetic, anti-obesity, anti-HIV-1, anti-Alzheimer's, cholesterol-lowering, calcium absorption-enhancing, and hemostatic effects. They also possess superior cellular transduction properties compared to chitosan and are fully absorbed through the intestinal epithelium. Therefore, they have been shown to be suitable for tissue engineering, drug or gene delivery, and combating multidrug resistance in chemotherapy. Their medical applications rival, and may even surpass, those of chitosan. To date, no evidence has been found that chitosan and chitosan oligosaccharides can induce the secretion of interferons or derived growth factors in the body. However, studies have shown that chitosan can induce the release of platelet-derived growth factor-AB (PDGF-AB) and transforming growth factor-β1 (TGF-β1) from platelets (He Liu et al., "A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing," RSC Adv., 2018, 8, 7533). The above research results on glucosamine compounds and organic germanium compounds clearly demonstrate that the pharmacological properties of glucosamine compounds and organic germanium compounds complement each other, exerting a synergistic effect in medical efficacy, resulting in the excellent efficacy of the drug of the present invention.

[0016] Summary of the Invention

[0017] The present invention provides a drug prepared from an organic germanium compound and a glucosamine compound, and its use. The present invention also has the following objectives, including: (1) preparing a liquid organic germanium drug that is convenient to use and free from contamination by solid germanium dioxide; (2) developing a method for preparing chitosan solutions that is simple, has a short reaction time, and is free from contamination by toxic components; (3) preparing a drug that combines the biochemical properties and medical effects of organic germanium and glucosamine compounds; and (4) preparing a drug that can produce endogenous transforming growth factor in humans and animals, promote rapid wound healing, and inhibit wound exudate production.

[0018] To achieve one, some, or all of the above-mentioned objectives, or other objectives, the present invention involves reacting an organic germanium compound containing a carboxylic acid group (-COOH) with a glucosamine compound. The protonation of the reactive amine group (-NH2) of the glucosamine compound by the hydrogen ion of the carboxylic acid group of the organic germanium compound results in the preparation of a water-soluble salt drug. The salt drug is highly water-soluble, dissociates in tissue fluid, and exhibits the biochemical, pharmacological, and therapeutic properties of its components. These biochemical, pharmacological, and therapeutic properties include analgesic, anti-inflammatory, antioxidant, anti-hypoxic, immunomodulatory, antiviral, and interferon secretion-inducing, transforming growth factor-binding, effects derived from the organic germanium compound, as well as antibacterial, antioxidant, anti-inflammatory, antihypertensive, drug / DNA delivery, antidiabetic, anti-obesity, anti-HIV-1, anti-Alzheimer's, cholesterol-lowering, calcium absorption enhancement, hemostatic, cell transduction, and complete intestinal epithelial absorption derived from the glucosamine compound. The complementary nature of these effects gives the present drug a wide range of remarkable medical benefits, including, but not limited to, promoting wound healing (including trauma, lacerations, abrasions, knife wounds, burns, scalds, sunburn, acne, diabetic ulcers, and bedsores caused by prolonged bed rest). The following examples demonstrate the excellent medical effects of the present drug, using Ge-132 with chitosan and chitosan oligosaccharides, and its use in promoting wound healing.

[0019] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention, which can be implemented in accordance with the contents of the specification, and to make the above and other purposes, features and advantages of the present invention more obvious and easy to understand, the following specifically cites preferred embodiments and describes them in detail with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] FIG1 shows the time-dependent changes in the wound size ratio of rats in Comparative Example 1.

[0021] FIG2 shows the time-dependent changes in the wound size ratio of rabbits in Example 1.

[0022] FIG3 shows the time-dependent changes in the wound size ratio of rabbits in Example 2.

[0023] FIG4 shows the time-dependent changes in the wound size ratio of rabbits in Example 3. DETAILED DESCRIPTION

[0024] Organic germanium compounds with a carboxylic acid group suitable for preparing the drug of the present invention include, but are not limited to, organogermanium sesquioxide, germanes, germatranes, spirogermanium compounds, germanium porphyrines, and germanocenes. The most typical of these is bis-carboxyalkyl germanium sesquioxide, the chemical formula of which is shown in Formula (II):

[0025] In the formula, R1, R2, and R3 can be H, substituted or unsubstituted lower alkyl groups such as methyl or ethyl, aryl, or hetaryl, or substituted or unsubstituted amino or amido groups; X can be H, K, Na, a basic amino group, aryl, or hetaryl group. When R1, R2, R3, and X in formula (II) are H, the product is bis(carboxyethyl)germanium sesquioxide, a solid polymer with the molecular formula n(GeO 1.5 When X in formula (II) is K, Na, a basic amino group, an aryl group, or a heteroaryl group, acidification and crystallization with concentrated hydrochloric acid yield a white Ge-132 powder. Furthermore, the chemical formula of hetero-nitrogen germanium tricyclic compounds (germatranes) is shown in formula (IV):

[0026] In the formula, R is a cinnamic acid group [-CH(C6H4OH)CH2COOH], a caffeic acid group [-CH(C6H3(OH)2)CH2COOH] or one of their derivatives. The spiro-germanium compound is at least one selected from the following: 3-(2,8,9-trioxa-aza-1-germatricyclo-[3,3,3,0]-undecane-1-yl)caffeic acid, 3-(2,8,9-trioxa-aza-1-germatricyclo-[3,3,3,0]-undecane-1-yl)-10-hydroxy-decanoic acid, acid), 3-(2,8,9-trioxa-aza-1-germatricyclo-[3,3,3,0]-undecane-1-yl)-10-methoxy-decanoic acid), 3-(2,8,9-trioxa-aza-1-germatricyclo-[3,3,3,0]-undecane-1-yl)-10-methoxy-decanoic acid, acid), 3-(2,8,9-trioxa-aza-1-germatricyclo-[3,3,3,0]-undecane-1-yl)-10-phenyl-decanoic acid.

[0027] Ge-132 is the most representative bis-carboxyalkyl germanium sesquioxide, and its structural formula is shown in formula (III):

[0028] Ge-132 is soluble in water. The reaction when it dissolves in water is shown in formula (1): n(GeO 1.5 CH2CH2COOH)2+3nH2O=2nGe(OH)3CH2CH2COOH (1)

[0029] When Ge-132 dissolves in water, it forms a carboxylic acid called 3-(trihydroxygermyl)propanoic acid (THGP), whose chemical formula is Ge(OH)3CH2CH2COOH.

[0030] Description of drug preparation principles

[0031] Chitosan is one of the glucosamine compounds used in the present invention and is used as an example. As shown in Formula (I), chitosan's chemical structure contains three common reactive functional groups: an amino group, a primary hydroxyl group, and a secondary hydroxyl group. This makes it more reactive than typical polysaccharides, but it is insoluble in water. Chitosan's various medical applications primarily involve forming it into sols, gels, films, or fibers. Liquefaction is a primary challenge in producing these pharmaceutical formulations. Previous studies have revealed that chitosan is soluble only in acidic solutions. This solubility is due to the protonation of its reactive amine groups by hydrogen ions. Its solubility is affected by the degree of deacetylation, the distribution of acetyl groups on the molecular chain, the pH of the acid, the acid molecular structure, and other ions present. Consequently, studies have shown that the maximum pH at which chitosan can dissolve ranges from pH 6 to pH 6.5 (Domard A. "pH and cd Measurements on a Fully Deacetylated Chitosan: Application to CuII-polymer Interactions" Int. J. Biol. Macromol., 9, 98, 1987; JW Park and HK Choi, "Acid-Base Equilibria and Related Properties of Chitosan" Bull. Korean Chem. Soc., Vol. 4, No. 8, 1983; Rinaudo, M.; Pavlov, G.; Desbrières, J. "Solubilization of Chitosan in Strong Acid" Medium" Int. J. Polym. Anal. Charact. 5, 267–276, 1999), in which Rinaudo et al. further pointed out that when more than 50% of the reactive amine groups in the chitosan molecule are protonated, chitosan is in a dissolved state.

[0032] The carboxylic acid THGP formed when Ge-132 dissolves in water is a weak acid. According to experiments conducted by Sara M. Ogwapit et al. ("Analysis of Ge-132 and development of a simple oral anticancer formulation", Bioscience Horizons, vol. 4, No. 2, June 2011), the solubility of Ge-132 in 25°C water is 1.28 g / 100 ml. At this concentration, the pH of the solution is 3.06-3.12. Experiments conducted in the present invention show that THGP solutions, like acetic acid solutions, have a good solubility for chitosan. This solubility is due to the protonation of the reactive amine groups (-NH2) of chitosan by the hydrogen ions of the carboxylic acid groups of THGP. The reaction is shown in Equation (2).

[0033] The product of the reaction of formula (2) is chitosan-N-3-trihydroxygermyl propionate (chito-N-THGP), a water-soluble salt compound in the form of a polycationic polymer. It dissociates in water into 3-(trihydroxygermyl) propionate anion (Ge(OH)3CH2CH2COO-) and protonated chitosan cation (chito-NH3 + ), thus revealing the biochemical properties of this plasma.

[0034] Experiments conducted by the present invention show that the reaction of formula (2) is a gentle process. When chitosan is added to a 3-(trihydroxygermanyl)propionic acid solution, the chitosan is protonated to produce a pale orange-yellow, viscous reaction solution containing chito-N-THGP, which is a colloidal solution. As the amount of chitosan added increases, the pH and viscosity of the reaction solution increase accordingly. According to experiments conducted by the present invention, when preparing a drug using chitosan with a degree of deacetylation of 91.35% and a molecular weight of 100-130 kDa, the viscosity (at 25°C) rises to approximately 15,000 cp when the dissolved chitosan reaches 5% of the total weight of the reaction solution. When the chitosan addition reaches a certain level, the carboxylic acid group hydrogen ions of THGP are depleted, and the reaction of formula (2) terminates. The chitosan no longer dissolves, and the reaction solution becomes turbid, no longer clear and transparent, with a pH of approximately 6.

[0035] Chitosan's degree of polymerization, degree of deacetylation, and molecular weight are subject to variability, which can affect its solubility and make drug quality difficult to control. Therefore, the present invention utilizes acids with good chitosan solubility, including but not limited to acetic acid, formic acid, hydrochloric acid, or sulfuric acid, as pH adjusters. This eliminates the need for 3-(trihydroxygermyl)propionic acid to dissolve chitosan. This allows the dissolution of each functional raw material to be achieved within the desired desired ratio while ensuring the drug's stable appearance and properties. In addition to being ideal pH adjusters, these acidic agents can also replace the role of 3-(trihydroxygermyl)propionic acid, allowing the amounts of chitosan and 3-(trihydroxygermyl)propionic acid to be freely adjusted during drug preparation, without being restricted by reaction equivalents. Therefore, pH adjusters not only help prepare pH-stable, transparent, and clear drug solutions, but also serve as viscosity regulators. The drug can achieve the desired viscosity without the need for an external thickener, ensuring the purity of the drug ingredients and reducing contamination. Similarly, the addition of alkaline pH adjusters, including but not limited to ammonium hydroxide or alkali metal and alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, and calcium hydroxide, can promote the dissolution of organic germanium compounds with carboxylic acids, freeing their content in the drug solution from being limited by their reaction equivalent with chitosan. This not only adjusts the pH, but also allows the drug of the present invention to further contain highly water-soluble salts formed by these alkaline agents and the organic germanium compounds, which helps increase the concentration of 3-(trihydroxygermanyl)propionate (Ge(OH)3CH2CH2COO-) in the drug and the corresponding medical efficacy, which is also part of the present invention. According to the present invention, the salts formed by the above-mentioned alkaline agents and Ge-132 all have a good effect on promoting wound healing. Because calcium ions also have a hemostatic effect, when calcium hydroxide is used as the alkaline agent, the prepared medicine can also help stop wound bleeding. This will be experimentally demonstrated in the examples.

[0036] The chito-N-THGP-containing solution prepared from chitosan has similar typical properties to other chitosan organic acid solutions, including: (1) the solution is in a sol state (i.e., a sol solution) when acidic and transforms into a gel state when neutral or alkaline; (2) the salt compound (chito-N-THGP) generated by the reaction is insoluble in organic solvents, including alcohol. Therefore, in addition to being able to prepare the sol solution into ointments or liquids, these properties can also be utilized to prepare it into other forms for use. For example, the sol solution may be prepared by making it neutral or alkaline and gelling it to form a hydrogel. The hydrogel may be dispersed in 95% alcohol or an organic solvent to obtain a precipitate, which may then be filtered and dried under low-temperature vacuum to form a powder. Alternatively, the sol solution, alone or in combination with other suitable polymers such as, but not limited to, polyvinyl alcohol (PVA), may be electrospun using electrospinning technology to form fibers, fiber membranes (El-Refaie Kenawy et al., Journal of Controlled Release 81 (2002) 57–64; Zheng-Ming Huang et al., Composites Science and Technology 63 (2003) 2223–2253; Y. Liu et al., J. Biomed. Mater. Res. Part B: Appl Biomater. 90B: 492–502, 2009), or nonwoven fabrics. Furthermore, experiments conducted by the present invention have shown that the sol has good miscibility with glycerin. By mixing it evenly with an appropriate amount of glycerin (boiling point 290°C), applying it in a thin layer, and then heating it to remove moisture, a soft, transparent film can be formed. Therefore, in addition to liquids, ointments, and emulsions, the present drug can also be formulated into powders, films, fibers, fiber membranes, or non-woven fabrics. The present drug can optionally contain at least one auxiliary agent and is suitable for both in vivo and in vitro administration.

[0037] In addition to chitosan, the present invention also utilizes chitosan oligosaccharides and 3-(trihydroxygermanyl)propionic acid for pharmaceutical preparation. Experimental results using chitosan oligosaccharides with an average molecular weight of 1270 Da, obtained by enzymatic degradation, showed that aqueous chitosan solutions exhibited a weak acidity, with a pH of 5.4 at 25°C for a 1% solution. Concentration had a minimal effect on pH, with no significant change in pH when the concentration increased from 1% to 10%. However, temperature had a significant effect on pH. Increasing temperature decreased pH. For example, in a 10% chitosan oligosaccharide solution, the pH decreased from 5.65 to 4.49 as the temperature increased from 20°C to 55°C, demonstrating a nearly linear pH change.

[0038] The protonation reaction of chitosan oligosaccharide with 3-(trihydroxygermyl) propionic acid can also be represented by formula (2). The product of the reaction is N-3-(trihydroxygermyl) propionate chitosan oligosaccharide (COS-N-3-trihydroxygermyl propionate, COS-N-THGP), which is also a salt compound. It will dissociate into 3-(trihydroxygermyl) propionate anion (Ge(OH)3CH2CH2COO-) and protonated chitosan oligosaccharide (COS-NH3 + ) cations and therefore possess the biochemical properties of both.

[0039] The preparation of drugs using chitosan oligosaccharides follows the same procedure as that using chitosan. When chitosan oligosaccharides are added to a solution of 3-(trihydroxygermanyl)propionic acid, they dissolve immediately, forming a brown reaction solution. Because chitosan oligosaccharides are highly water-soluble, their dissolution is not entirely controlled by protonation of the amine group. Furthermore, the pH of the reaction solution is significantly lower than that of drugs prepared using chitosan oligosaccharides. The protonation reaction with chitosan oligosaccharides consumes more Ge-132, promoting its dissolution. Therefore, similar to the dissolution of chitosan, the concentration of 3-(trihydroxygermanyl)propionate in the reaction solution can be higher than its saturation concentration in a Ge-132 aqueous solution. Because chitosan oligosaccharides have a low degree of polymerization and molecular weight, the viscosity of the reaction solution is also low, eliminating the problem of high viscosity affecting handling and the need to lower the pH to aid dissolution of the chitosan oligosaccharides. Instead, an alkaline solution, including but not limited to ammonia or alkali metal and alkaline earth metal hydroxides such as sodium hydroxide and calcium hydroxide, can be added as needed to moderately raise the pH or, if necessary, to aid dissolution of Ge-132, thereby increasing the concentration of 3-(trihydroxygermanyl)propionate in the drug as described above. When calcium hydroxide is used as a pH adjuster, it can also help hemostasis of wounds due to the hemostatic effect of calcium ions. The drug of the present invention prepared from chitosan oligosaccharides can also be formulated into liquids, ointments, or powders by adding appropriate excipients and additives. Chitosan gel can also be added to form films for use. However, due to its high hygroscopicity, moisture-proof treatment is required when formulating the powder to prevent sticking.

[0040] Based on the above description, the preparation steps of the drug of the present invention are summarized as follows: (1) Material Preparation: Based on the quantity and composition of the drug to be prepared, the required raw materials are prepared, including an organic germanium compound such as Ge-132, a glucosamine compound such as chitosan or chitosan oligosaccharide, a pH adjuster, and deionized water. (2) Pre-heating with Water and Stirring: The required amount of deionized water is placed in a heated stirring reaction tank and stirred, with or without heating as appropriate. (3) Adding the Organic Germanium Compound: The required organic germanium compound is measured by dry weight into the reaction tank and dispersed and dissolved in the water under stirring. , to produce 3-(trihydroxygermanyl)propionic acid; (iv) adding the glucosamine compound: when the water temperature reaches a predetermined temperature, the glucosamine compound is introduced into the reaction tank, and excessive introduction is avoided to avoid poor dispersion of the solid powder particles; (v) continuously stirring to complete the protonation reaction: after the addition of the glucosamine compound is completed, heating is stopped (if any) at an appropriate time, and the pH of the reaction solution is continuously observed until it stabilizes to confirm the completion of the protonation reaction; (vi) adjusting the pH: adjusting the reaction solution to a predetermined pH using a pH adjuster; (vii) adjusting the weight: adding deionized water to adjust the weight to a predetermined value to complete the preparation.

[0041] The above steps are simple and easy to perform. The following are some key considerations for operational efficiency and drug quality control: In step (1), because chitosan and chitosan oligosaccharides are hygroscopic, they must be stored in a moisture-proof manner. The water content must be determined before preparing the materials. The reaction equivalent varies depending on the molecular structure, so batch-by-batch analysis is required. In step (2), the amount of water placed in the reaction tank must be sufficient to allow for the subsequent addition of a pH adjuster solution (although the amount used is small). Heating can be used with or without heating. Heating can promote the dissolution of Ge-132 and accelerate the reaction, but subsequent cooling is time-consuming. If the room temperature is below 25°C, heating is recommended, but preferably should not exceed 50°C. In step (3), the organic germanium compound can be added all at once or in portions. It can be added before or after the water is heated. In step (4), chitosan or chitosan oligosaccharides are added in batches according to the desired drug composition. When chitosan is used to prepare the drug, the viscosity of the reaction solution increases with the addition of chitosan, and the flow pattern of the solution during stirring may also change. Therefore, excessive addition should be avoided, which may result in poor particle dispersion. A stirrer suitable for high-viscosity fluids should also be used. When chitosan oligosaccharides are used to prepare the drug, due to their high water solubility and low viscosity, viscosity does not affect the operation. In step (5), a stable pH is measured, indicating that the protonation reaction is complete and the subsequent steps can be performed. Because the pH of the solution is affected by temperature, temperature correction is required during measurement. In step (6), temperature correction is required during pH adjustment, and attention must be paid to the potential damage to the pH electrode caused by the viscosity of the drug solution to prevent this from affecting the measurement accuracy. In step (seven), the adjustment of the ingredients should be based on weight to avoid the influence of temperature changes and can be carried out without waiting for the temperature to drop.

[0042] The above-mentioned drug is first disclosed in the present invention. To make the features, objectives, and advantages of the present invention more clearly understood, the use of the drug in promoting wound healing is specifically cited below as an example, and detailed description is provided with reference to the accompanying drawings. This example should not be construed as limiting the types of drugs disclosed in the present invention or their use in other medical applications.

[0043] Comparative Example 1 of Wound Healing Effect: According to the literature, Hiroko Matsumoto et al. used Ge-132 solution, also known as 3-(trihydroxygermanyl) propionic acid solution, to conduct a study on the healing of skin wounds in rats (Hiroko Matsumoto et al., "Restorative effect of organic germanium compound (Ge-132) on dermal injury", Wound Medicine, Vol. 15, Dec. 2016, P6-10). The rats were treated with an isotonic solution containing 1.8 wt% Ge-132 and compared with a normal saline solution as a control group. The study found that on days 1, 3, 7, and 14, the sizes of the treated wounds were 1.45 ± 0.23 cm2, respectively. 2 )、1.45±0.13cm 2 、0.780±0.124cm 2 and 0.050±0.013cm 2 The wound sizes of the control group treated with physiological saline solution (PS) were 1.77±0.36cm 2 、1.73±0.13cm 2 、0.942±0.150cm 2 and 0.108±0.049cm 2 For the sake of clear comparison, based on the above results, the wound size ratios on days 1, 3, 7, and 14 were compared, with the median of the wound area on day 1 being 100%. The results are shown in Figure 1. The two curves representing the changes in wound size ratios in the treated and control groups during the treatment period are very close, indicating that the Ge-132 isotonic solution does not have a particularly significant effect on promoting wound healing.

[0044] Example 1: Example 1 is a wound healing treatment using the drug of the present invention to demonstrate the advancement of the present invention. The drugs used in the present invention include: (1) containing 3 wt% Ge-132 equivalents and 4.5% chitosan equivalents (code: 3% Ge-CTS), (2) containing 3% Ge-132 equivalents and 4.5% chitosan equivalents (code: 3% Ge-COS), and (3) containing 1.5% Ge-132 equivalents and 2.25% chitosan equivalents (code: 1.5% Ge-CTS), which is obtained by diluting 3% Ge-CTS with deionized water. For comparison with Comparative Example 1, the organic germanium components of the above experimental drugs are measured based on the Ge-132 equivalents contained. The so-called 3% Ge-132 equivalents means that the weight of Ge-132 used in the preparation of the drug is 3% of the weight of the produced drug. According to the molecular weight of Ge-132 (339.4222), the molecular weight of 3-(trihydroxygermanyl)propionic acid (199.75), and the reaction equivalence relationship of formula (1), a 3% Ge-132 content is equivalent to a 3.531% 3-(trihydroxygermanyl)propionic acid content, or a 1.284% germanium content (atomic weight 72.64).

[0045] These examples are intended to demonstrate the wound healing effects of the present invention and should not be construed as limiting the scope of the present invention. Furthermore, to understand and compare the wound healing effects of different Ge-132 salts, wound healing experiments were conducted using a 3% Ge-132 equivalent calcium 3-(trihydroxygermanyl) propionate solution (codenamed: 3% Ge-Ca). This was used as Example 2 to examine the wound healing effects of Ge-132 alkaline earth metal salts.

[0046] Preparation of experimental drugs:

[0047] Prepare according to the above methods and steps.

[0048] Material preparation:

[0049] The organic germanium compound used was Ge-132. Commercially available Ge-132 powder with a purity of at least 99.95% was dissolved in 95°C deionized water to form a saturated aqueous solution. The solution was then filtered through Whatman No. 3 qualitative filter paper. The filtrate was collected in a beaker and stirred, cooled to room temperature to allow the Ge-132 to crystallize. The crystalline slurry was then vacuum filtered, and the filter cake was washed with deionized water and dried to a moisture content of 0.15%. Finally, it was crushed into a powder for later use. The glucosamine compounds used were chitosan and chitosan oligosaccharides, both commercially available products (Chengli Industrial Co., Ltd.). Chitosan had a degree of deacetylation of 91.35%, a molecular weight of 100-130 kDa, and a moisture content of 9.47 wt%. Chitosan oligosaccharides had a degree of deacetylation of 91.35%, an average molecular weight of 1270 Da, and a moisture content of 8.32 wt%. The pH adjuster used was a 10 wt% aqueous solution of glacial acetic acid. Because chitosan is hygroscopic, it was dried to remove water and then weighed for dry weight.

[0050] Preparation of experimental drug 3% Ge-CTS:

[0051] The preparation is carried out as follows: (1) 180 g of deionized water is placed in a 500 ml beaker, 6 g of dry weight Ge-132 powder is added, electric stirring is started, and the mixture is heated to 50°C; (2) 9 g of dry weight chitosan (i.e., 1.5 times the weight of Ge-132) is slowly added to the stirring Ge-132 solution; (3) After the chitosan is added, stirring is continued and the temperature is maintained for 30 minutes, then heating is stopped and the temperature is allowed to drop to 25°C. The pH of the resulting solution is measured to be 6.03; (4) The pH of the resulting solution is adjusted to 5.81 using a pH regulator; (5) Deionized water is added to adjust the weight to 200 g, and the mixture is mixed to obtain a light orange-yellow viscous solution. The 9 g of chitosan (1.5 times the weight of Ge-132) used in the above preparation was determined to be the weight required for the protonation reaction with 6 g of Ge-132.

[0052] Preparation of experimental drug 3% Ge-COS:

[0053] Preparation was performed using the same procedure and temperature as for the 3% Ge-CTS, using the same Ge-132, but without a pH adjuster. The resulting 3-(trihydroxygermanyl) propionic acid chitosan oligosaccharide solution was a low-viscosity, brown solution containing 3 wt% Ge-132 equivalents and 4.5 wt% chitosan oligosaccharide equivalents. Its pH was measured at 3.02 at 25°C. To facilitate comparison with chitosan, the weight of chitosan oligosaccharide used was also 1.5 times that of Ge-132.

[0054] Preparation of experimental drug 3% Ge-Ca:

[0055] (1) 180 g of water was placed in a 500 ml beaker and stirred with an electromagnetic heating stirrer. 6.01 g of Ge-132 powder (6 g dry weight) was then added to the water. (2) 1.31 g of Merck GR grade Ca(OH)2 powder was added to the beaker and heated to 45°C to dissolve the Ge-132 and Ca(OH)2 powders. After 30 minutes, water was added to adjust the total weight of the solution to 200 g. The solution was then filtered through Whatman No. 3 qualitative filter paper to obtain an experimental drug 3% Ge-Ca containing 3 wt% of Ge-132 equivalent. The pH at 25°C was measured to be 7.04.

[0056] Animal tests on wound healing:

[0057] The experimental animals were 100-day-old New Zealand minimally diseased (MD) white rabbits weighing between 2.3 and 2.5 kg. Two days prior to the experiment, the rabbits were accustomed to wearing a lick-resistant back cover. The cover prevented licking but did not interfere with defecation. It could be easily removed for drug application and observation and photography. On the day of the experiment, the rabbits' mid-back area was shaved. Then, one or two wounds measuring 1.5 cm x 1.5 cm (actual size based on measurement) were made on either side of the spine in the shaved area, with the wound edges spaced 4 cm apart. After anesthesia was achieved by injecting Xylestesin-A at the designated wound site, the wound was created using a biopsy punch and scalpel. The skin and flesh above the fascia were removed, and the wound was pressed with medical gauze to stop bleeding. The wound was then cleaned with saline and dried with a medical cotton ball before drug application.

[0058] The wound dosage was 0.3 ml per wound for the first 7 days. After 7 days, the dosage was halved due to wound shrinkage. After application, the wounds were covered and secured with 3M breathable polyurethane film (Tegaderm™ Film, St. Paul, MN). Treatment was repeated every 24 hours, and wound size was measured using the area measurement function in Photoshop after photographing. The control group wounds were treated identically, except that no treatment was applied.

[0059] Comparison between Example 1 and Example 2:

[0060] Example 1 used two drugs, 3% Ge-CTS and 3% Ge-COS, while Example 2 used 3% Ge-Ca. All three drugs contained a 3% Ge-132 equivalent concentration. Three rabbits were treated with each drug, in which two wounds were created on either side of the spine according to the above method. Three replicates of the same conditions were performed for each drug, along with a control group that received no drug. The wound sizes were measured on days 1, 3, 7, and 14. Table 1 shows the experimental results for Example 1 using two drugs, 3% Ge-132 and 3% Ge-COS, Example 2 using 3% Ge-Ca, and the control group. The data includes wound size and, for comparison purposes, the proportional change in wound size relative to the wound size on day 1 (i.e., 100%).

[0061] Table 1: Experimental results of Example 1 and Example 2

[0062] Generally speaking, surgical wounds, regardless of whether or not they're treated with medication, are likely to heal within about two weeks. When a medication promotes healing, the wound shrinks significantly faster in the initial stages of the experiment than in the untreated control group. Figure 2 shows the experimental results for three rabbits treated with each medication in Example 1 on days 1, 3, 7, and 14. The two curves represent the proportional change in average wound size between the treated and control groups, respectively, and the distance between the two curves represents the difference in wound shrinkage.

[0063] Figure 2 shows that regardless of whether 3% Ge-CTS or 3% Ge-COS was applied, the wounds shrank rapidly in the initial phase of treatment and maintained a significantly faster healing rate than the control group wounds throughout the treatment. The wound shrinkage rates for 3% Ge-CTS and 3% Ge-COS were very similar, with no significant difference. The control group wounds showed significant enlargement on the third day, which can be attributed to the occurrence of inflammation, while the treated wounds did not experience this phenomenon. The experimental results of Example 1 fully demonstrate that Ge-CTS and Ge-COS have a very significant promoting effect on wound healing, which can be attributed to the production of transforming growth factor and the inhibition of inflammation by the drugs.

[0064] Example 2: Wound healing experiment of Ge-132 alkaline earth metal salts

[0065] The proportional change in average wound size in Example 2, performed with 3% Ge-Ca, is shown in Figure 3. Both the wounds treated with 3% Ge-Ca and the control group expanded on day three, but the extent of expansion in the treated group was significantly less than in the untreated control group. The wound shrinkage rate in the treated group was superior to that in the control group and also superior to the comparative example of 1.8% Ge-132 isotonic solution shown in Figure 1, but inferior to the effect of 3% Ge-CTH and 3% Ge-COS in Example 1.

[0066] Example 3: Healing effect experiment of low concentration Ge-CTS

[0067] To understand the effect of the concentration of the present invention's drug on wound healing, wound healing experiments were conducted on three rabbits, numbered D, E, and F, using 1.5% Ge-CTS. The wounds were created using the same method as in Example 1, with each rabbit receiving a wound measuring approximately 1.5 cm x 1.5 cm (the actual size is subject to measurement) on either side of the dorsal spine. 1.5% Ge-CTS was applied to one wound at the same dosage as in Example 1, while the other wound remained untreated, serving as a control. The experimental results are shown in Table 2.

[0068] Table 2: Experimental results of Example 3

[0069] Figure 4 shows the changes in the average wound area ratio on days 1, 3, 7, and 14 in Table 2 (with day 1 as 100%), indicating that the wounds treated with 1.5% Ge-CTS were significantly smaller than those of the untreated control group within the first 7 days. This is comparable to the effect of 3% Ge-CTS in Example 1, and is significantly better than the effect of 3% Ge-Ca in Comparative Example 1. This indicates that even at half the concentration, Ge-CTS still has a significant effect in promoting wound healing, and is significantly better than the 1.8% Ge-132 isotonic solution in Comparative Example 1.

[0070] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment, it is not intended to limit the present invention. Any technician familiar with the present profession can make slight changes or modifications to equivalent embodiments of equivalent changes using the methods and technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A drug, characterized in that The drug contains a water-soluble salt compound, which is prepared from an organic germanium compound with a carboxylic acid group and a glucosamine compound with a reactive amine group, and is prepared by protonating the reactive amine group of the glucosamine compound through the hydrogen ion of the carboxylic acid group of the organic germanium compound; wherein the glucosamine compound is selected from at least one of the following: glucosamine monosaccharide, chitosan oligosaccharide, and chitosan polysaccharide.

2. The drug according to claim 1, characterized in that The drug is a drug with biological activity and medical use derived from organic germanium components and glucosamine components contained in the drug.

3. The drug according to claim 2, characterized in that The medical uses of organic germanium components are any of the following: anti-inflammatory effect, antiviral effect, effect of inducing secretion of interferon, effect of deriving transforming growth factor, and effect of healing wounds.

4. The drug according to claim 2, characterized in that The medical uses of glucosamine are any of the following: antibacterial effect, anti-inflammatory effect, and hemostatic effect.

5. The drug according to claim 1, characterized in that The organic germanium compound with a carboxylic acid group is at least one selected from the following: organic germanium sesquioxide, germanane compound, hetero-nitrogen germanium tricyclic compound, spiro-germanium compound, germanoporphyrin compound and diocene germanium compound.

6. The drug according to claim 1, characterized in that The molecular weight of the chitosan oligosaccharide is less than 3,900 Da, and the degree of deacetylation is greater than 90%. The molecular weight of the chitosan polysaccharide is less than 130 kDa, and the degree of deacetylation is greater than 90%.

7. The drug according to claim 5, characterized in that The monomer chemical formula of the organic germanium sesquioxide is shown in formula (II): In the formula, R1, R2, and R3 can be H, substituted or unsubstituted lower alkyl groups such as methyl or ethyl, aryl, heteroaryl, substituted or unsubstituted amine or amide, etc.; X can be H, K, Na, a basic amine, aryl, or heteroaryl, etc.

8. The drug according to claim 7, characterized in that The organic germanium sesquioxide is bis-carboxyethyl germanium sesquioxide (Ge-132).

9. The drug according to claim 5, characterized in that The chemical formula of the hetero-nitrogen germanium tricyclic compound is shown in formula (IV): In the formula, R is a cinnamic acid group [-CH(C6H4OH)CH2COOH], a caffeic acid group [-CH(C6H3(OH)2)CH2COOH] or any other group containing a carboxylic acid group.

10. The drug according to claim 5, characterized in that The spiro-germanium compound is at least one selected from the following: 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl) caffeic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl)-10-hydroxy-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl)-10-methoxy-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl)-10-ethoxy-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl)-10-phenyl-decanoic acid.

11. The drug according to claim 1, characterized in that The drug is administered in any of the following forms: solution, emulsion, ointment, hydrogel, powder, film, non-woven fabric.

12. The drug according to claim 1, characterized in that The medicine further contains at least one additive selected from the following: antibiotics, wetting agents, vitamins, thickeners, excipients, and pH regulators.

13. The drug according to claim 12, characterized in that The pH adjuster is at least one of the following: acetic acid, formic acid, hydrochloric acid, sulfuric acid, ammonia water, sodium hydroxide, calcium hydroxide, and magnesium hydroxide.

14. A wound healing drug prepared by the following steps: Providing an organic germanium compound having a carboxylic acid group; A glucosamine compound is provided, wherein the glucosamine compound has an active amine group capable of undergoing a protonation reaction and is selected from at least one of the following: glucosamine monosaccharide, chitosan oligosaccharide, chitosan polysaccharide; The organic germanium compound and the glucosamine compound are mixed in water to allow the carboxylic acid group to protonate the active amine group to form a drug solution; The pH and weight adjustments of the drug solution were performed, as well as the addition of excipients.

15. The wound healing medicament according to claim 14, characterized in that The organic germanium compound with a carboxylic acid group is at least one selected from the following: organic germanium sesquioxide, germanane compound, hetero-nitrogen germanium tricyclic compound, spiral germanium compound, germanium porphyrin compound and dicyclopentadienyl germanium compound.

16. The wound healing medicament according to claim 14, characterized in that The molecular weight of the chitosan oligosaccharide is less than 3,900 Da, and the degree of deacetylation is greater than 90%. The molecular weight of the chitosan polysaccharide is less than 130 kDa, and the degree of deacetylation is greater than 90%.

17. The wound healing medicament according to claim 15, characterized in that: The monomer chemical formula of the organic germanium sesquioxide is shown in formula (II): In the formula, R1, R2, and R3 can be H, substituted or unsubstituted lower alkyl groups such as methyl or ethyl, aryl, heteroaryl, substituted or unsubstituted amine or amide, etc.; X can be H, K, Na, a basic amine, aryl, or heteroaryl, etc.

18. The wound healing medicament according to claim 17, characterized in that The organic germanium sesquioxide is bis-carboxyethyl germanium sesquioxide (Ge-132).

19. The wound healing medicament according to claim 15, characterized in that: The chemical formula of the hetero-nitrogen germanium tricyclic compound is shown in formula (IV): In the formula, R is a cinnamic acid group [-CH(C6H4OH)CH2COOH], a caffeic acid group [-CH(C6H3(OH)2)CH2COOH] or any other group containing a carboxylic acid group.

20. The wound healing medicament according to claim 15, characterized in that The spiro-germanium compound is at least one selected from the following: 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl) caffeic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl)-10-hydroxy-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl)-10-methoxy-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undecane-1-yl)-10-ethoxy-decanoic acid, 3-(2,8,9-Trioxa-aza-1-germanetricyclo-[3,3,3,0]-undec-1-yl)-10-phenyl-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanetricyclo-[3,3,3,0]-undec-1-yl)-hydroxycinnamic acid.

21. The wound healing medicament according to claim 14, characterized in that: The step of adjusting the pH value of the drug solution further comprises using at least one pH adjusting agent selected from the group consisting of acetic acid, formic acid, hydrochloric acid, ammonia water, sodium hydroxide, and magnesium hydroxide.

22. The wound healing medicament according to claim 14, characterized in that This medicine is used to treat any of the following wounds: trauma, lacerations, abrasions, knife wounds, burns, scalds, sunburn, acne, pressure sores, diabetic ulcers, etc.

23. The wound healing medicament according to claim 14, characterized in that: The drug is prepared and used in any of the following forms: solution, emulsion, ointment, hydrogel, powder, film, non-woven fabric.

24. A wound healing drug, characterized in that: The wound healing medicine contains salts formed by an organic germanium compound with a carboxylic acid group and at least one compound selected from the following: glucosamine monosaccharide, chitosan oligosaccharide, chitosan, ammonium hydroxide, alkali metal hydroxide, and alkaline earth metal hydroxide.

25. The wound healing medicament according to claim 24, characterized in that The alkali metal hydroxide is at least one selected from the following: sodium hydroxide, potassium hydroxide, lithium hydroxide; the alkaline earth metal hydroxide is at least one selected from the following: calcium hydroxide, magnesium hydroxide.

26. The wound healing medicament according to claim 24, characterized in that The organic germanium compound with a carboxylic acid group is selected from at least one of the following: organic germanium sesquioxide, germanane compound, hetero-nitrogen germanium tricyclic compound, spiral germanium compound, germanium porphyrin compound and dicyclopentadienyl germanium compound.

27. The wound healing medicament according to claim 26, characterized in that The organic germanium sesquioxide is bis-carboxyethyl germanium sesquioxide (Ge-132).

28. The wound healing medicament according to claim 26, characterized in that The chemical formula of the hetero-nitrogen-germanium tricyclic compound is shown in formula (IV): In the formula, R is cinnamic acid [-CH(C6H4OH)CH2COOH], caffeic acid [-CH(C6H3(OH)2)CH2COOH] or any other group containing a carboxylic acid group.

29. The wound healing medicament according to claim 26, characterized in that The spiro-germanium compound is at least one selected from the following: 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undec-1-yl) caffeic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undec-1-yl)-10-hydroxy-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undec-1-yl)-10-methoxy-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undec-1-yl)-10-ethoxy-decanoic acid, 3-(2,8,9-trioxa-aza-1-germanium tricyclo-[3,3,3,0]-undec-1-yl)-10-phenyl-decanoic acid.