TWI252103B - Pharmaceutical compositions for the treatment of painful, inflammatory and ulcerative conditions of moist epithelial surfaces such as mucositis, stomatitis and Behcet's syndrome - Google Patents

Abstract

Pharmaceutical compositions comprising as active ingredients effective doses of hyaluronic acid, glycyrrhetinic acid and polyvinylopyrrolidone, for the treatment of painful, inflammatory and ulcerative conditions of moist epithelial surfaces such as mucositis, stomatitis and Behcet's syndrome.

Description

1252103 V. INSTRUCTIONS (1) About the use of hyaluronic acid, glycyrrhetinic acid and facial music composition to treat the pain and hairiness caused by the wet surface of the mouth, oropharynx: in mucositis m Besett's technique The two terms of background mucositis and angular keratitis often interact with each other. Mucositis is a description of an effect that affects the intestines. This inflammatory response may be caused by exposure to chemora. Mucositis usually presents erythema or appears scattered. From local to diffuse ulcer keratitis means an inflammatory reaction that affects oral mucus, but not necessarily ulceration. Through drug therapy, radiation may cause or develop angular cheilitis. Inflammatory keratitis can be distinguished from mild to severe; severe horny disease Many women will have ulcers in the genitals during the specific period of the menstrual cycle, especially when the genital ulcer is very serious, which will lead to closed urine, and need to be more ^ Agent. The most severe ulcer condition is called Bessel's syndrome. In the following description, the general word mucositis is also used to study the role of mucositis and support this application. After receiving chemotherapy or radiation, the erythema Appears, but it usually takes five to seven days to appear. It will develop into ulcerative mucositis, sometimes severe enough to require mesangitis to involve the mouth, oropharynx, and polypyrrole I from the mouth to the anus. Vaginal, rectal disorders (including but not, but still There are toxic inflammatory therapeutic agents in the stomach, or radiation, burning-like damage. This inflammation, especially the reaction, will cause a sore-free ulcer and a white pain relief group. The intestinal reaction may be chemotherapy or strong. Oral feeding. And in the same way. Sometimes the agent and analgesic itself. Wai. Will usually be treated within three days. Sticky stomach.

I2S2l〇3 V. Inventive Note (2) Here we will stick the 膣 Μ pharynx, esophagus and;: the disease is limited to more accessible parts such as mouth and mouth patients receiving chemotherapy, ancient degrees of mucositis, θ The ratio (from 3〇% to 40%) will result in treatment. Until now, there is no heart for you ^ ^ The need for an effective and convenient treatment is to try to use ^ ^ treatment is feasible, and solve the problem to alleviate the symptoms. Pain, sedatives and oral hygiene measures to go further, this is especially the case with a card; Western patients, AIDS patients, older and weaker patients, and heartless non-Hodgkin's lymphoma Mucositis is often found in patients with disease-induced necrosis factor (TNF) and dry-blood BRM treatments such as interleukin-2 and tumor therapy. The invention discloses that the activation of lymphocytes by Ba, and the present invention have been surprisingly found to be effective in the treatment of both human acid and polyethylene. The prevention of non-instrument and radiation is generally applicable to dentistry. Therefore, in the first aspect of the invention, hyaluronic acid, glycyrrhetinic acid and polyhedral in the form of -cm 1 are mixed, and the excipients and auxiliary ketones are mixed. In order to be active, the substance can be adsorbed on the epidermis, so <2, the material having the drillability and the slickness, for example, ... is suitable for topical application to the surface cells, 1 small 艮, oropharynx and esophagus and other parts. Another aspect of the invention relates to the use of pyrrolidone for the preparation of a medicament for the inflammation of the epidermis of the sputum of the sputum, the sputum, the sputum, the sputum, the sputum, the sputum, the sputum, the sputum, the sputum, the sputum, the sputum CODE\90-09\90118290.ptd 1252103 V. INSTRUCTIONS (3) Limited to oral mucosa, especially mucositis and angular cheilitis. The composition of the present invention is a type of slightly viscous liquid (colloid). Capable of forming on the epithelial surface, such as the oral mucosa The effect of film and coating, but not limited to the mouth-to-mouth mucosa. The weight percentage of hyaluronic acid in the composition is from 〇·〇1% to 5%, and · 〇·1% is better. Hyaluronic acid can also It is in the form of a sodium salt, preferably produced in a biotechnological manner, and has a molecular weight of 丨·6 χ 1 〇6~2 · 2 X i 〇6 Da 〇

Polyvinylpyrrolidone or polyallyl g (P Vp ) is a suspension and linking reagent widely used in the technology. In the formulation of the present invention, the weight percentage is from 1% to 2% by weight, preferably between 5% and 10,000%. The weight percentage of the glycyrrhetinic acid in the composition is preferably from 〇·〇1% to //weight. It is preferably used in the polymer of polyene acetone, for example, K_3 (^, jK-丨 acetone, preferably K-90 polyolefin) The same can be used for the composition of the present invention, for example, a topical application of a tackifier, a surface agent, a stabilizer, a preservative, a flavoring agent, Aroma, sweetener-bioadhesive

1252103 V. INSTRUCTIONS (4) A co-solvent These excipients include or different molecular weight polymeric sesame oil, EDTA, sodium sodium, aspartame, and the like. Any useful activity of the composition of the present invention, an anti-inflammatory agent, a town comprising a quaternary amine salt, for example, finally, a dosage form, a dosage form of the present invention, such as a sachet, a pharmaceutical drug, can be added. Dilution) It is best to eat after the meal. Treatment can be continued into the pharmaceutical composition without contraindications. The use of the hyaluronic acid in the formulation according to the invention has the effect of adhering to the formula, thereby reducing the wettability of the composition, such as an antibacterial agent or a chlorhexidine combination therapy: Almost formula can be lightly oxalic acid and oral mucosa, with a cellulose derivative, acrylic or mercapto propylene polymer, ethylene or propylene glycol, polyethoxylated hydrogenated bismuth sodium salt, sodium sorbate or Potassium, dextrin, and saccharin are generally used in the manufacture of mouthwashes and oral liquids to further contain other active ingredients, with complementary or agents/disinfectants, anti-fungal agents, analgesics, and the like. Effective antibacterial agents can be single or multiple dose water bottles, injection bottles, glass bottles, and the like. It will be determined by a number of factors, for example, depending on the severity of the disease, essentially taking 10 to 50 ml per day for 2-3 minutes, 3 times a day or more, to provide good treatment and preventive effects, usually 5 to 10 days. Because the hair is not toxic, the reason for the longer-term treatment to achieve good therapeutic results is the combination of polyvinylpyrrolidone and the protective membrane for the exposed nerve endings to promote the syndrome and treat the wound. Furthermore, it has beneficial effects, it can protect the mucous membrane from

\\312\2d-code\90-09\90118290.ptd Page 7 1252103 V. Invention Description (5) "" One - Further irritating damage. The following examples will explain the present invention in more detail. Qualitative-scheduled composition percentage sodium hyaluronate n 0. 06 9. 0 6.00 2. 94 0· 3 0· 3 1· 5 0. 27 0· 1 0. 5 0. 16 0· 1

Glycyrrhetinic acid PVP Maltodextrin propylene glycol sorbate sodium benzoate hydroxyhydroethyl cellulose hydrogenated hydrazine » sesame oil PEG - 4 0 disodium EDTA gas benzene killing spice (Glycyrrhiza compound 2717) saccharin sodium pure water At the time of preparation, the sodium maltodextrin 78. 44 water was first placed in a vortex emulsifier, and then a mixture of sodium sorbate and sodium EDTA was added, followed by addition of hyaluronic acid and stirring of the compound after each addition of one component. Until the additive is completely dissolved. Afterwards, PVP was slowly added under the scrambled Fengu &/ηΛ DVD pack and vacuum (30 mmHg) until completely dissolved. Then add the saccharin and hydrogen oxyethyl cellulose in the order of the main time. Place the mixture under the direct air, 廿 4士 A soil·*, 隹 直, /, and continue to stir until completely dissolved. again

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Page 8 V. Description of invention (6) t-ene = hydrogenated perennial oil PEG_4°, perfume, chlorpyrifos, and addition: = mixture of oxalic acid, added after the addition, until 30 minutes added After completion, the mixture is continuously stirred under vacuum. The concentrate is produced in a combination of 1 ml or 15 ml in a single-dose vial, diluted with 3 〇 50 ml of water, and then diluted. The ready-to-use product is prepared by purifying the above composition with a dilution of 50/° and taking a 200 ml or 30 ml device vial.

Bed test Patients from 30 to 60 years of age, one of whom was aged 3 to 4 years old, were evaluated for AIDS patients treated with anti-retroviral therapy. The patients have a number of causes of oral inflammation and toxin infection: 1 2 medical records for oropharyngeal mucositis; 4 medical records for oral aphthous injury; 4 medical records for trauma after trauma; 3 medical records for oral lichen planus癣; 3 medical records are stomatitis caused by radiation therapy;

Three medical records are side effects of oral surgery; one medical record is white spot disease. The composition of Example 1 containing 15 ml of the drug capsule was diluted 1:4 with water to treat the patient. The micro-viscous solution was left in the mouth for 2 to 3 minutes during which time it was evenly distributed over the entire surface of the oral mucosa by mouthwash and agitation. This solution was then spit out.

C:\2D-OODE\90-09\90118290.ptd Page 9 1252103 V. INSTRUCTIONS (7) The formula is used three times a day for 60 minutes before meals for seven consecutive days. At the end of treatment, the extent of inflammation and injury, the reduction or disappearance of solid and semi-solid foods and liquid pharyngeal difficulty, and the duration of activity of the product are assessed. After the first application, more than 80% of patients experienced pain relief within a few hours and were able to eat. This effect lasts for three or four hours. After 3-4 days of treatment, about 60% of the medical records of the oral mucosa have healed. The percentage reached 90% after the end of treatment. There was only one pathological symptom in the remaining 3 years of medical records, but the symptoms were significantly improved compared with before the start of treatment, which significantly improved the quality of life and restored a normal, changing diet. Example 3 Two patients with sore throat (sore with sore throat) cannot relieve pain by an analgesic or other local agent. The composition of Example 1 containing 15 ml of the drug capsule was diluted 1:4 with water to treat the patient. Leave the solution in the mouth for about one minute, during which time the mouth is made to make good contact with the throat tissue. The solution is then spit out. Within ten minutes, the patients felt that the symptoms of their sore throat were significantly reduced and lasted for hours.

C:\2D-CODE\90-09\90118290.ptd Page 10 1252103 Schematic description

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Claims (1)

1252103 : Case No. 90118290 Λ _ 5f a titiii 0 Amended on 92. 12. 1 1 » · Replacement of this six, the scope of the patent application 1. A treatment for the tide, the package is active pharmaceutical ethylene sputum application 2. If Tackifier, sweet 3 · For example, containing fiber ethylene or sodium, mountain 4 · such as more into a group of ketones. Application for special agents, odorants, application of special-derived propylene sulphate - Sodium citrate application, including the application of special agents, anti-profit range, biological range, propanol, poly or clock, other areas of profit The range of pain, inflammation and ulceration on the wet epithelial surface of the fungicide contains an effective dose of hyaluronic acid, glycyrrhetinic acid and a poly component, and is mixed with an excipient and an auxiliary drug, and is suitable for the pharmaceutical composition of the first item, and further encapsulating , stabilizers - preservatives, flavoring agents, flavoring agents, auxiliary solubilizers. The pharmaceutical composition according to item 2, which further comprises an enoxalic acid or a methacrylic acid polymer or copolymer, ethoxylated hydrogenated castor oil, EDTA, benzoic acid dextrin, sodium saccharin, and aspartame. The pharmaceutical composition according to any one of items 1 to 3, which has an active ingredient which has complementary or useful effects. A pharmaceutical composition according to item 4, which comprises an antibacterial agent, an analgesic agent, an anti-inflammatory agent, a sedative, and a topical 5. For example, a disinfectant anesthetic. 6. The pharmaceutical composition according to claim 1 of the patent scope, having the following composition percentage, urinary licorice PVP, malto succinate, sodium succinate, sodium citrate 0.10. 06 9.0 6. 00 2. 94 0. 3 \\A326\总档\90\90118290\90118290 (replace)-2, ptc Page 12 1252103 Fix 〇· 3 1· 5 〇. 27 〇· 1 〇· 5 0.16 Case No. 90118290 Patent application range benzoic acid nashydro oxyethyl cellulose hydrogenated E sesame oil PEG-40 disodium EDTA chlorinated pyridine herb (Glycyrrhiza compound 2717 ) Sodium saccharin pure water ' as claimed in claim 1 of the scope of the medical turtle. People ^. Treatment of oral mucosa and oropharynx and esophageal internal -,, and mouth 'is used for the treatment of membranous inflammation and sputum sputum, as well as for the treatment of vaginal and 'intestinal I 2 2 , especially sticky (including but not limited to vestibulitis) And the inflammatory disease of Besett's disease group