TW201216859A - Disinfectant and antiseptic formulation having reduced iodine content - Google Patents

Abstract

The invention is related to the use of the solution of elemental iodine prepared in an organosiloxane solvent as antiseptic or disinfectant agent and formulations suitable for such use.

Description

201216859 VI. INSTRUCTIONS OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to disinfecting and antiseptic formulations having reduced iodine content and exhibiting excellent tissue compatibility. The formulations of the present invention contain elemental forms rather than iodine in the form of ions or complexes. Another object of the invention is a method of preparing a disinfecting and antiseptic formulation of the invention. Another object of the invention is the use of an iodine solution prepared with a oxoxane as a disinfectant or preservative. [Prior Art] The disinfection, antiseptic and bactericidal activities of moths have long been known. Among the elements used for disinfection, hydrazine is the least active element. The elemental state is caused by the I knife, and the appearance is a light brown purple metallic luster. It is also known that iodine and iodine vapor are irritating purple smoke S (the name of iodine is the name of the genus: 1〇deS), which means "purple". Iodine is in the following organic non-polar liquids.../imitation, carbonized carbon, carbon disulfide (soluble benzene, color, color), ethanol, ether, acetone (the color of the solution is light brown = color:: = 1). In the solution of tetrahydrogen, tetracycline or complex human heart, iodine is partially or completely converted into ion complex: shape 2: difficult: in water and polar solvent, it produces an unstable solution containing ions and u. The halogen element (especially gas and her) Yan ion form (sub-ethnic /,) widely from its elemental form or its oxygen yin popular s dish, hypoxanthine sputum, m ^ l female for anti-corrosion purposes, only use touch. Yuan::) used as a disinfectant' However, the agent, which rapidly destroys bacteria in the test tube, and broad-spectrum broad-spectrum bactericidal 'bacteria, viruses and fungi, as well as some native 201216859 animals. After the use of the magnetic preparation known from the prior art, most of the microorganisms were destroyed within 1 minute. During this period, most of the damage occurred in about the first 15-30 seconds. The resistance to angina is unknown, and it is effective against a wide range of pathogens because iodine destroys Gram-positive f rTram乂.., λ (Gram_P〇sltlve) and Gram-negative bacteria, viruses and fungi, and some protozoa And its different stages of development. Bacteria, fungi, and spores of some viruses require longer periods of action to achieve inactivation. Destroying different pathogens requires different amounts of hardness. The individual sensitivity of the pathogenic strain/viral strain depends on the iodine form present in the formulation, its concentration, pH, temperature, exposure time. Therefore, when using 1% by weight of iodine, the 90% of bacteria are destroyed. The exposure time was 9 sec; in the case of a 7 wt% strength nail, this exposure time was reduced to 15 seconds. When the iodine solution having a concentration of 1 to 2% by weight is applied, the time required for the virus to be inactivated is 3 to 20 minutes. The general characteristics of the disinfecting and preservative efficacy in the prior art are the MIC value (minimum inhibitory concentration) of the active agent. The MIC value is the disinfectant/preservative concentration that prevents the visible growth of a given microorganism. For example, in the case of a yeast belonging to the genus Candida (genus C (10) heart), the MIC value measured for the polyvinylpyrrolidone iodine complex is between 〇.001 and 〇25 weight percent (RS Traboulsi, PK Mukherjee, MA Ghannoum: In vitro activity of inexpensive topical alternatives against Candida spp. isolated from the oral cavity of HIV-infected patients. Int. J. Antimicrob. Agents 3 1 (2008) pp. 272-276). Iodine solutions prepared in different solvents have been used for centuries as disinfectants 4 201216859 or preservatives. Most commonly, an alcohol solution of elemental iodine and potassium iodide is used, in which the element is hard in the form of a complex with a moth clock. The active disinfectant is elemental iodine released from the ionic form and the complex, respectively. However, the medical iodine produced in this manner is unstable, rapidly dried, and the object in contact with it is severely discolored, corrosive, and strongly irritating the tissue. Because of q, it has reduced the use of moths. ' Recently, a variety of pharmaceutical formulations (eg, solutions, suppositories, creams, foams, oral disinfectants) use a water-soluble complex of iodine formed with a high molecular weight polymer (eg, polyvinylpyrrolidone-iodine) in place of iodine. . The complexes contain iodine in an alcohol-free soluble form as an ionic complex. = Toxicity and preservative effects are produced by the action of iodine in the form of elements released from the complex (5 2 mg / 1 concentration). These formulations are more convenient and less iodine-free and can be washed away from the skin. A disadvantage of forming a dimer with a high molecular weight polymer is the lack of a stable H pH dependence, the necessity to use a large amount of stable excipients and the unpleasant sensation produced by the viscous film layer of the vehicle polymer remaining on the application area. According to the prior art, there are known hard-containing formulations containing a water-soluble iodide or an iodate-form moth dispersed in a viscous liquid or an elastic solid vehicle. These products are used for (four) charging of drinking water, and the content of strontium in sputum does not meet physiological requirements. The water soluble content of such products is released by long-term slow diffusion from a hydrophobic, viscous or crosslinked elastomeric matrix. A. The circumstance of the diagnosing patents No. 283407, No. 2834〇8, No. 284521, No. 285525, No. 357519, and No. The organic briquette elastomer 201216859 is dispersed in a viscous polyoxyxide oil. U.S. Patent No. 4,384,960 discloses the use of (IV) for water disinfection, for wound preservation, and for sputum supplementation, in which a liquid formulation is filled: there is a benefit of providing a fixed dose opening and a member for holding solid particles. During use, the container is filled with water and a hydrazine-containing formulation, and a granular formulation such as solid crystalline hydrazine or strontium is added. In this way, a small amount of hard is dissolved and a hard aqueous solution containing about 200-tog/m moth is formed. In this solution, ❹ 素 moth, Wei and citrate forms exist. The hard-containing pellets can be formed by dispersing moths in a polycalyx rubber (cautch) or a polyoxoelastomer. A disadvantage of this composition is that the solubility of iodine in water is low and significantly dependent on temperature. Therefore, the dissolution rate is low, and the concentration of the aqueous solution containing the moth will be regarded as the time when the magnetic solution is taken out from the composition, and then the temperature and the slave are used each time. This effect may make the use of the composition unnecessarily complicated and render the sterilization ineffective. The expansion and membrane/permeability of the iodine and iodine complexes in the two compartments separated by a polyoxynitride membrane have been investigated to optimize sustained release of the magnetically contained formulation (κ.

Takikawa, M. Nakano, T. Arita, Chem. Pharm. Bull. 26(3) pp. 874-879 [1978]). It has been found that g-type complexes exhibit significantly lower permeability than elemental angstroms. The solubility of iodine in organooxane and the corresponding thermodynamic processes (such as changes in solubility parameters) are studied in detail (H. Watanabe, T. Miyauchi, J-Chem. Eng. Japan, Vol. 6(2), 109-114 Page [1973]). The researchers found that the solubility of iodine in organic polyoxane at room temperature was about 5-7 g/l (〇·5-0.7 weight percent). By increasing the degree of polymerization, the solubility is lowered by 6 201216859, which is 0, and the night is although the hydrazine is soluble in many organic solvents and the solution is 2 = 'However, the solvent suitable for dissolving and filling is mostly for living organisms: 1: Living organisms are incompatible. Therefore, these solutions cannot be used as an anti-caries or preservatives. Because it contains a solution with "molecular enthalpy m:::," (where 峨...ΐ exists) by releasing the element 峨, it must contain higher than the effective concentration of the microorganism in the solution. A few times or even a ώ 之 之 Free 7L use machine ^ Shao S 3 orders of magnitude moth. Since the iodine-containing compound relies on the free element of the ruthenium compound, the product of the ruthenium compound lacks satisfactory stability, temperature activity, skin type, enthalpy and several other factors: π solution. Therefore, in order to achieve reliable disinfection or preservation, many times the complex is used to provide the necessary free concentration. The iodine on the surface of the body or the iodine transferred in the body in the form of a smear or a moth-like compound causes unnecessary harm to the environment, which causes skin, clothing and articles; It is well tolerated, but its long-term presence on the skin or presence at a second degree may result in excessive sensitivity and rash. Gas knives, the shortcomings of iodine-containing formulations known from the prior art are complex operations, rapid decomposition and short storage caused by the risk of soiling the body and clothing. Uncertain disinfection and antiseptic effects and environmental hazards. Sexual and physical storage period is inversely proportional to its efficacy. A formulation with a large stability that exhibits poor performance = a long period of release releases a significantly smaller amount of sputum, hence politics. Formulations that release their iodine contents faster provide a higher elemental 201216859 iodine concentration and exhibit good efficacy. However, its shelf life is therefore shorter. Therefore, there is a particular need for stable, effective, fast-acting and optionally long-acting disinfecting and anti-corrosive iodine formulations suitable for industrial production, in which iodine is used in a low concentration in a form different from its complex. The formulation can be used with minimal contamination and irritation risk and is suitable for minimizing tissue damage due to preservative treatment of areas where tissue damage has occurred, such as wounds. The goal of the research and development work of Sigma is to develop a sterilized and antiseptic formulation suitable for meeting the above requirements. The present invention has solved this object. The invention relies on the discovery of m people: by dissolving the element (4) in the trimeric organic polyoxo compound, a disinfection and antiseptic solution can be produced, which even exhibits excellent disinfection and antiseptic effect under the name of the agricultural degree, is stable, and does not lead. (iv) Discoloration and contamination' and most surprisingly, it is compatible with living organisms and shows little tissue damage, irritation or hypersensitivity. PREPARATION The prior art is not described for use as an antiseptic or disinfectant in an organopolyphosphorus or anthraquinone-type solvent. The present invention is directed to an agglomerated solvent which is more versatile than a polysulfide solvent and, where appropriate, other auxiliary forms; a solution of a volatile hydrazine is used for disinfection and as a preservative. In order to achieve this, you can transfer the solution in a solvent suitable for the bismuth oxy-type solvent to something to be treated. . The surface of the device is 'and when needed'. When it is suitable for processing: D dish or pack is removed. We have surprisingly found that the iodine solution prepared in the 虱 2012 8 201216859 虱 命 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 There is virtually no tissue damage or irritation in the situation. Another object of the present invention is a formulation containing elemental iodine in a cerium-oxygenated vehicle. [Embodiment] During use in accordance with the present invention, a solution prepared in a polyoxo-type solvent and having other components may be transferred to a surface to be treated by a brush (10) moistened with the solution, Or the object to be treated can be immersed in the solution of the invention. In this § §, the table is honest, "Life stone 々 r , . . . 2 」 或 或 或 或 或 或 或 或 或 或 或 或 或 或 或 或 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示 表示The polysubstituted polyoxosite can be linear (polysulfuric acid and _elastic rubber), cyclic, / knife-branched (- some poly-stone) or cross-linked (poly-stone) Resin)...The molecular weight of polylactic acid may exceed 700,000 g/m〇h The boiling temperature and viscosity of polysulfate are mainly determined by the degree of polymerization. Derivatives having a dimerization degree are volatile and free-flowing; # by increasing the concentration of 聚, 2, and the upper viscosity 仟 by k 冋. Exceeding a specific degree of polymerization limit or 9 into the parent's polyoxyl can be made in the form of an elastic, partially or fully solid polyoxyelastomer or a rubber. The body "hydrogen is replaced by a hydrolyzed group (4) (4) or a mixture thereof. For example, according to the published European Patent Application No. ninth method, hydrolysis of trimethyl gas sulphate in the presence of aqueous hydrochloric acid a mixture of polyoxopoly 201216859, which is purified and distilled by distillation. The use of polyoxin in medicine was previously due to sufficient purity for medical purposes and The burden of costing polyoxyxides is frustrated. For example, ophthalmic oxygen used in ophthalmology is often contaminated with monomers or oligomers, thereby damaging product quality and also causing health problems. The oil comprises a group of polyoxygenated oils. The high volatility polyoxyphthalic oil is a cosmetic or pharmaceutical excipient that volatilizes from human skin within a 6 hour period after application to the skin and is of a quality suitable for the manufacture of pharmaceutical formulations. The use of polyfluorene oxides with different degrees of polymerization in the formulation of cosmetic and pharmaceutical formulations and nutrients is known. High molecular weight oils and elastomeric rubbers are used as vehicles or film formers. In the form of a dispersing or stabilizing agent. According to the present invention, there is provided a preservative or disinfecting formulation comprising elemental iodine and a decyl oxane vehicle and optionally other active agents or excipients. Disinfecting and preserving iodine containing formulations are primarily In three forms. Rapid evaporative formulations (eg, aerosols, elixirs, solutions, soaks) have the general character of an iodine-containing solution that acts within seconds and evaporates from the surface within 1 minute. The formulations may be, for example, an aerosol. , an elixir, a solution, a foaming form, which is suitable for a surface which is easy or less accessible for antisepsis or disinfection (for example, an aerosol, an elixir, a solution) or a cavity (aerosol, foam). A preservative for the treatment of body surface damage or body cavity treatments. These fast-evaporating formulations are suitable as preservatives for medical preservatives, for first aid and for handling minor injuries. These formulations evaporate quickly from the skin and do not cause body or clothing. Dyeing 201216859 A medium-term, long-lasting effect that lasts for at least 1 minute but no more than 1 dose, or may be effective if needed. The characteristic is that the release of iodine to the surface is small. After the release of iodine, it is evaporated from the surface. The formulation of these formulations in a few minutes (solution, nail, cream, gel, ointment H powder, Suppositories, cotton swabs, etc.) The door is effective for more than 1 hour and can be removed by washing from the preservative or disinfecting treatment site. It has been surprisingly found that the stability of the solution of the iodine in the solvent of the present invention is uncertain. Different from the form of ions and complexes, in the decomposition stage = forming the element responsible for disinfection and antiseptic effect. The stability of the formulation of the invention: the limitation of the evaporation of the self-packaging material, and the heat sensitivity and instability; • The moth-containing formulation known from the prior art is born to lose efficacy immediately. It has also been surprisingly found that the formulation of the invention does not cause any acupuncture, irritation, tissue damage or any other discomfort. Administration The use of the formulation of the invention prevents the wound treatment material from sticking to the wound. The formulations of the present invention are themselves sterile (due to the disinfection and preservation of moths) and remain sterile for an indefinite period of time in a suitable package. The simplest form of the formulation of the invention consists of iodine dissolved in a suitable oxime. 'However, if desired, the formulation may contain other excipients or pharmaceutically active agents. The film former as an excipient prevents air and environmental effects from approaching the treated area, thereby reducing the risk of repeated infections. 1 The film forming agent includes, but is not limited to, a lipophilic polymer, preferably a polyoxygenated oil. Such as dimethyl polymethodone or dimethocone or organic compound of higher molecular weight. Formulations may contain additional anti-corrosion agents, 5G disinfectants, 201216859 cosmetic agents or suitable for handling healthy bites, such as promoting tissue regeneration or wounds, antibiotics, antivirals or antifungals. Pharmaceutical active ingredients on the surface of injured skin Healing agents. In fact, there is no limit to the quality or composition of the mixture of the diarrhea or the diarrhea used as a vehicle. Money burning products with different degrees of polymerization can be used for US or medical music applications. The individual compounds, products or mixtures thereof can be used in the preparation of the formulations of the invention. The evaporation rate of the formulation of the present invention depends on the composition of the vehicle, and is most dependent on the concentration of the volatile polyoxo component and the degree of polymerization. The octagonal oxygenated derivative having a higher polyoctave evaporates slowly and is simultaneously used as a film forming agent for the iodine-containing film on the treated surface. Preferably, the Oxygen-Oxide oligomer is hexamethyldiazepine, octamethyltrioxetane and decamethylcyclopentaoxane. "Our people have found that the antiseptic and disinfecting formulations of the present invention comprising angstroms dissolved in the shovel are effective against certain microorganisms at a concentration of 001.001 weight percent iodine. The iodine concentration can be 0.001 weight percent and iodine depending on the intended use. Between the saturated concentrations in the azide solvent used. For low molecular weight volatile siloxanes, the saturation concentration is in the range of 0 5 - 0. 8 weight percent, and at a constant temperature with the molecular weight of the oxirane and The degree of polymerization is significantly reduced and it has been found that formulations of the invention having a concentration of G.2-G.3 by weight angstroms are exposed to all test organisms at room temperature within 0.25 to 1 minute (co/z ·), Pseudomonas aeruginosa (~ (10) office (four) like aewgz · «read), Staphylococcus aureus ($ 师 / 〇 c〇c (10) suspicion), Bacillus subtilis (Bac (1) w ah mountain · all show antiseptic effect. Therefore, The formulation of the best embodiment of the invention of 201212859 contains 5% by weight, most typically 0.25 重量% iodine. In the case of rapid evaporation of the formulation, the iodine concentration should be set due to the shorter exposure time. Higher range regions. When a formulation of the invention having a medium or long-term effect is required, it is preferred to set the iodine concentration in the lower concentration range region for longer exposures. The formulation of the present invention may be based on pharmaceutical technology. Manufactured by known methods. Iodine and other active ingredients or excipients selected as appropriate are generally dispersed or dissolved in the lowest molecular anaerobic component under continuous agitation, and the resulting mixture and other groups of formulations are obtained. The homogenization was carried out together. Example 1 A quick-acting aerosol formulation containing iodine by weight of iodine dissolved in oxy- smoldering hexamethyldioxane octadecyl trioxane 峨 at room temperature After stirring, 79.85 g of 19.9 g 0.25 g was dissolved in hexamethyldiazepine. The addition of octadecyldioxane was obtained by the preparation of ^^π only 忖< In the aerosol bottle of the pump, and sealed. Example 2 3: 1% by weight of iodine and oxirane solvent to prepare iodine (immediately effective) composition 98.75 g octadecyl trioxane 13 201216859 Polyoxyalkylene 1〇g 0.25 g The iodine is dissolved in octadecyltrioxane at room temperature with stirring. Thereafter, dimethyl is added to the mixture and the mixture is dissolved and dissolved. The solution thus obtained is filled with Disperse or drip the bottle of the accessory and seal it. Example 3 Lipogel containing a 0.4% by volume of oxy-combustion (permanent action) Composition of octadecyltrioxane polyglycol Mixture of body with decamethylcyclopentanoxane (eg D〇W Corning ST Elastomer 10) 90.0 ε Iodine 0.25 g Iodine is dissolved in octamethyltrioxane at room temperature with stirring, β + The liquid helium gel base is mixed and homogenized at room temperature. The gel thus obtained is filled in a plastic test tube or a jar and sealed. Example 4 Test bacteriostatic efficacy in Escherichia coli (ATCC 8739, American Type Culture Collection, Manassas, Virgmia, USA), Green Pus g (ATCC9 () 27), Staphylococcus aureus (ATCC 6538), and Dry Grass (4) ( The bacteriostatic efficacy test of the s weekly ligand of the present invention was carried out in a mixed culture of ATCC 6633). A mixture of strain cultures after 24 hours of incubation (incubation temperature:) was used in the test. The experiment was carried out under aseptic conditions. Using a sterilized pipette, 5 ml of the test substance (with the composition of the present invention having a weight of 0.05-0.5 weight of stone octagonal alpha (containing 1 〇〇m of the present invention) and the field of the moon J (3 with (10) mg/) Mi povidone 峨 and the iodine concentration is 1〇·

The aliquot of the Betadine solution) was transferred to a 3 - 3 sterile test tube. The ά ά W h ^ g conjugate culture was added to each test tube. Dijon Start (4) exposure time, and broadcast a part of Chiang Kai-shek at 2 〇, 2 5 and 30 minutes exposure time to disinfect the sword 1 4 , only the 4, and 4 and the control preparations to treat each fine to contain neutralization After ^ 匕 液 液 液

Caso gravy medium (MAST). During the preparation of the subculture, the Caso broth medium was used in 10 ml of the wound, and the filling was filled with 1 ml of 20 詈 詈 ... 靖 靖 靖 靖 靖 靖 靖 靖 靖 靖 靖 靖 , , , , , , , , , , , , Test the antibacterial effect of the disinfectant). Subcultures were incubated at a temperature of 36 C for 72 hours. The subcultures in which bacterial growth was observed were inoculated to the fresh medium of the same composition by (10) 35_... liver pro-test, and the results were read after 48 hours. As a control solution, the bacterial culture was examined by inoculating a portion of the medium containing the neutralizing component but not using the test or control toxicant, corresponding to the tested disinfectant solution (etadine). No bacterial proliferation was observed in either the right primary or secondary culture, and the preservation and/or/shawl effect was considered satisfactory. If the bactericidal action occurs in the same incubation time or shorter incubation time as observed in the case of the control disinfectant (Betadin), the antiseptic/disinfection test formulation is judged to be suitable. Example 5 Test the bactericidal effect using the contact plate method 5 · 1 · Medium composition for use with contact plates 15 201216859 'The medium consisting of a sterile contact plate: 15.0 g 5.0 g 5.0 g 17.0 g 0.7 g 1.0 g Digestively digested protein soy peptone sodium chloride agar Phospholipid L-histamine sorbitan-monooleate 5. 〇g -TW6en 80 2.0 ml pH: 7·3±0·2 5 _2 _ Test method 〇·1 ml part of the mixture of Example 4 The fine g culture (after time) was transferred to the 3-3 contact plate and allowed to dry. Three plates were incubated at a temperature of 36 C for use as a positive pair of 0.2 ml aliquots of the test formulations of the present invention. ,: another 3 = treated with the same volume of Betadin solution on the surface of the antiplate. The plate was incubated at one degree 724:: the average sentence was dispersed at 5 · 3 · After the evaluation of the incubation period, the number of the test preparation was counted, and the result was White w η. ^ Right on the group Luo, 2 liquid treatment The results of the plates were compared to the mean initial = fall number calculated as the flat dilution of the number of colonies obtained using the positive control to form a continuous fine (four) and the number of colonies could not be counted, and the dilution was used to repeat the test. 16 201216859 [Simple description of the diagram] No [Main component symbol description] No 17

Claims (1)

201216859 VII. Scope of application for patents: •• Use of organic oxoane-type vehicle and, if appropriate, 1 use of its excipient or medical ingredient (IV) liquid, its use agent or preservative 2 The use of an elemental moth solution prepared with an organic 11 oxygen vehicle for the manufacture of a sterilized or preserved pharmaceutical preparation. 3. A disinfecting or preservative pharmaceutical formulation comprising an elemental quinone as an active agent and a stone m-oxygen compound as a vehicle, optionally mixed with other pharmaceutically active ingredients or excipients. 4. A formulation as claimed in claim 3, characterized in that the vehicle is a volatile oxane or a mixture of such compounds. 5. The formulation of claim 3, characterized in that the vehicle comprises a volatile oxyhydrogen or a mixture of such compounds, a polyoxygen oil or a sulphuric acid elastomer component or a mixture thereof. 6. If the application of the scope of patent application 帛i is used, the characteristic is that the element is 峨; the concentration in the solution prepared by using the oxy-oxygen-type solvent is 0001-08, and the weight is preferably 1-.1-0.5% by weight, most Advantageously 〇2 〇3 by weight. 7. The formulation according to any one of claims 3 to 5, characterized in that the concentration of elemental iodine in the formulation is 〇〇〇1〇_8 by weight, preferably 〇.1-0_5 by weight. The percentage, most advantageously 0.2 - 0.3 weight percent. 8. The formulation according to any one of claims 3 to 5, characterized in that the phthalocyanine agent is hexamethylene dioxane, A methyl trioxane 18 201216859, and ten A cyclopentaoxane or a mixture thereof. 9. The formulation of any one of claims 3 to 5 in the form of an aerosol, solution, gel, elixir, cream or foam. 10. The formulation of any one of claims 3 to 5, characterized in that the formulation contains other excipients. 11. The formulation of claim 1, which comprises a film former, preferably a polyoxyxene or a polyoxyxene elastomer, preferably dimethicone as the other component. 12. The formulation of any one of claims 3 to 5, characterized in that the formulation contains other pharmaceutically active ingredients, preferably another antiseptic or disinfectant, antibiotic, suitable for treating health or damage A cosmetic agent for skin, a pharmaceutically active ingredient, preferably a tissue regenerating agent or an agent for promoting wound healing. A method of preparing a formulation according to any one of claims 3 to 5, which comprises hardly dispersing or dissolving the element in the lowest molecular weight component of the composition used in the formulation, and The mixture thus obtained is homogenized together with the other ingredients of the pharmaceutical formulation. Eight, schema benefits *