CN102058608B - New application of glucosamine in treating dental ulcer - Google Patents
New application of glucosamine in treating dental ulcer Download PDFInfo
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- CN102058608B CN102058608B CN201010601958.8A CN201010601958A CN102058608B CN 102058608 B CN102058608 B CN 102058608B CN 201010601958 A CN201010601958 A CN 201010601958A CN 102058608 B CN102058608 B CN 102058608B
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- glucosamine
- ulcer
- oral
- disease
- medicine
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Abstract
The invention relates to new application of glucosamine in treating dental ulcer, wherein the chemical name of the glucosamine is 2amino-2-deoxidation-D-glucose, and the glucosamine is an in vivo synthesized substance. The glucosamine comprises pharmaceutically acceptable salts such as hydrochloride, nitrate, sulfate, phosphate, hydrobromide, mesylate, citrate, and the like. The effective dosage of the glucosamine for treating dental ulcer is 0.01-5g, which is preferable for 0.1-1g, and more preferable for 0.1-0.5g.
Description
Technical field:
The present invention relates to a kind of novelty teabag of medicine, particularly a kind of novelty teabag of glucosamine, this novelty teabag is mainly used in oral ulcer,
Background technology:
Glucosamine, chemical name: 2-amino-2-deoxy-D-Glucose is the material of synthesis in human body, and being the important nutrient forming chondrocyte, is the natural tissues composition of healthy articular cartilage.With advancing age, the shortage of the glucosamine in human body is more and more serious, and articular cartilage is constantly degenerated and worn and torn.The U.S., Europe and Japanese a large amount of medical researches show: glucosamine can help repair and safeguard cartilage, and can stimulate the growth of chondrocyte.
Glucosamine in treating function, 1, adapt to disease: degenerative osteoarthritis of the knee, 2, adapt to disease: hyperosteogeny, 3, adapt to disease: meniscus injury, 4, disease is adapted to: patella, malacosis, 5, adapt to disease: cervical spondylotic radiculopathy, 6, adapt to disease: cervical spondylosis myeloid form, 7, adapt to disease: Cervical Spondylosis, 8, disease is adapted to: cervical spondylosis adrenergic type, 9, adapt to disease: synovitis, 10, adapt to disease: bursitis, 11, adapt to disease: hands bone
,arthritis, 12, adapt to disease: sufficient bone, arthritis, 13, adapt to disease: scapulohumeral periarthritis, 14, adapt to disease: tenosynovitis, thecal cyst, 15, adapt to disease: prolapse of lumbar intervertebral disc, 16, adapt to disease: rheumatic
,arthritis.
Be suitable for the crowd of maintenance, 1, crowd's type: crowd's scapulohumeral periarthritis of bending over one's desk working for a long time, 2, crowd's type: highly intensive labour crowd, 3, crowd's type: sport people, 4, crowd's type: special occupation crowd glucosamine has 3 Main Functions: first, the articular cartilage that repairing (or reparation) had been worn and torn already and surrounding soft tissue thereof, make articular surface keep smooth; The second, impel pass internode to generate more knuckle synovia, thus alleviate interarticular frictional force when walking; 3rd, antiinflammation, can eliminate arthritic symptom
Commercially, glucosamine mainly contains D-glucosamine hydrochlorate and two kinds, D-glucosamine sulfate, and in the clinical trial of China, D-glucosamine sulfate is similar to hydrochlorate therapeutic effect.Aminoglucose saccharide osteoarthrosis product can be divided into two classes substantially: one is the glucosamine formulations adding chemical antibiotic medicine, is subject to the strict control of FDA.This kind of preparation mainly contains glucosamine+ibuprofen, glucosamine+piroxicam.Two is numerous aminoglucose saccharide health foods, manages by dietary supplement series products.Wherein, aminoglucose saccharide health food can be divided into 3 classes again: one is simple glucosamine component preparation; Two is compound formulations of glucosamine+chondroitin sulfate; Three is glucosamine+other compound products becoming to be grouped into, as glucosamine+MSM (the osteoarticular health substance of a kind of protection), glucosamine+bromelain, glucosamine+vitamin D3, glucosamine+hyaluronic acid etc.
It was reported that, glucosamine has antiinflammatory, analgesic effect, has good curative effect to treatment rheumatic arthritis and gastric ulcer; Liver and kidney removing toxic substances can be participated in, play antiinflammatory liver protection effect; Can the growth of anti-bacteria.Also be the primary raw material of synthesis cancer therapy drug and antibiotic etc.Also can be used for food, cosmetics and feed additive, purposes is quite extensive.
Oral ulcer, is also called " aphtha ", is the superficial ulcer occurred on oral mucosa, large I from the grain of rice to Semen Glycines size, circular or oval, ulcer surface is recessed, congested around.Ulcer has the features such as periodicity, recurrent and self limiting, is apt to occur in lip, cheek, lingual margin etc.The cause of disease and mechanism of causing a disease are still indefinite.Inducement may be local wound, psychentonia, food, medicine, hormonal readiness change and vitamin or trace element deficiency.Systemic disease, heredity, immunity and microorganism may play an important role in its generation, development.Treatment is main based on topical therapeutic, and severe patient needs whole body therapeutic.
At present, the medicine for the treatment of oral ulcer has the powders such as Chinese medicine XILEI SAN, BINGPENG SAN, and Western medicine has the membrane of gargarism, aureomycin hydrochloride crystalline ointment and some medicines.Medicine membrane for oral ulcer has sitoesterol film (pharmaceutical factory, the Yellow River), rifamoin membrane (Beijing the 6th pharmaceutical factory), bacteriolyze enzyme membrane (biological pharmaceutical factory, Wuhan), clotrimazole film, Lac regis apis serous coat (Wuhan the 3rd pharmaceutical factory), dexamethasone Chinese medicine and western medicine compound stomatocase-treating films etc., above product has all had necessarily curative effect.
Oral ulcer is one of commonly encountered diseases, frequently-occurring disease, though non-very serious, the course of disease is long, is difficult to cure, and impact feed is even spoken, and its sickness rate accounts for the 10-15% of the total case of Outpatient Service Stomatology.A kind of easy to use, eutherapeutic pharmaceutical dosage form is wished in numerous patient pole.
Summary of the invention:
The present invention finds unexpectedly, and glucosamine can have good therapeutical effect to oral ulcer, therefore the invention provides a kind of new therapeutic use of glucosamine.
The present inventor is through research conscientious for a long time, and beat all discovery glucosamine is prepared into subsides painting preparation in oral cavity can have good therapeutical effect to oral ulcer, and does not find its untoward reaction in this product experimentation, safely, effectively.Again because there is no the report of glucosamine oral administration preparation at present both at home and abroad, therefore the present invention provides the purposes of glucosamine in treating dental ulcer from another aspect.
Glucosamine of the present invention, comprise the pharmaceutically acceptable salt forms such as its hydrochlorate, nitrate, sulfate, phosphate, hydrobromate, mesylate, citrate, it can form arbitrary form, comprise the pharmaceutically acceptable forms such as crystal form (comprising with water of crystallization with without water of crystallization), hydrate forms, preferred glucosamine hydrochloride and sulfate.These salt and different forms can be prepared according to method well known in the art.
Effective dose of the present invention is that glucosamine is losing the amount ranges in infections experiment for oral cavity.The present inventor is through repeatedly studying discovery, and the effective dose being suitable for glucosamine in treating dental ulcer is 0.01g ~ 5g, preferred 0.1-1g, more preferably 0.1-0.5g.
Therefore the invention provides the application of glucosamine in the medicine of preparation treatment oral ulcer.
Medicine of the present invention take glucosamine as the pharmaceutical preparations composition that active constituents of medicine is prepared into.
Pharmaceutical composition of the present invention, can contain medicine acceptable carrier as required, and medicine acceptable carrier in the formulation shared percentage by weight can be 0.1-99.9%.Pharmaceutical composition of the present invention, exists in a unit, and described unit dosage form refers to the unit of preparation, as every sheet of tablet, and every capsules of capsule, every bottle of oral liquid, granule every bag, often propping up of injection, every note etc. of patch.
Pharmaceutical composition of the present invention can be any pharmaceutically useful dosage form, these dosage forms comprise: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, cream, spray, drop, drop pill, patch, eye drop, buccal bioadhesive tablet, pigmenta pro cavo qris, oral cavity powder, paste etc.
Pharmaceutical composition of the present invention, the preparation of its oral administration can containing conventional excipient, and such as binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, flavoring agent and wetting agent, can carry out coating to tablet if desired.
The filler be suitable for comprises cellulose, mannitol, lactose and other similar filler.Suitable disintegrating agent comprises starch, polyvinylpyrrolidone and starch derivatives, such as sodium starch glycollate.Suitable lubricant comprises, such as magnesium stearate.The suitable acceptable wetting agent of medicine comprises sodium lauryl sulphate.
By mixing, fill, the method that tabletting etc. are conventional prepares solid oral composition.Repeatedly mix and active substance can be made to be distributed in those compositionss of a large amount of filler of whole use.
The form of oral liquid can be such as aqueous or oily suspensions, solution, Emulsion, syrup or elixir, or can be the composite dry products of a kind of available water before use or other suitable carrier.This liquid preparation can containing conventional additive, such as suspending agent, such as sorbitol, syrup, methylcellulose, gelatin, hydroxyethyl-cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agent, such as lecithin, anhydro sorbitol monooleate or arabic gum; Non-aqueous carrier (they can comprise edible oil), the oily ester of the such as ester of almond oil, fractionated coconut oil, such as glycerol, propylene glycol or ethanol; Antiseptic, such as para hydroxybenzene methyl ester or propyl p-hydroxybenzoate or sorbic acid, and if need, can containing conventional flavouring agent or coloring agent.
For liquid preparation, the fluid unit dosage form of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, this compound can be suspended or dissolve.The preparation of solution is normally by being dissolved in a kind of carrier by active substance, filter-sterilized before being loaded a kind of suitable bottle or ampoule, then seals.Adjuvant such as a kind of local anesthetic, antiseptic and buffer agent also can be dissolved in this carrier.In order to improve its stability, by freezing for this compositions after loading bottle, and under vacuo water can be removed.
Pharmaceutical composition of the present invention, applicable medicine acceptable carrier is optionally added when being prepared into medicament, described medicine acceptable carrier includes but not limited to following material, be selected from: mannitol, sorbitol, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin C, EDETATE SODIUM, Ethylenediaminetetraacetic Acid Calcium Salt, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and its derivates, alginate, gelatin, polyvinylpyrrolidone, glycerol, POLYSORBATE 80, agar, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.
The preferred pharmaceutical composition of the present invention is pharmaceutical dosage forms, most preferably the dosage form of oral local administration, as buccal bioadhesive tablet, buccal tablet, collutory, paste, spray, containing agent, aerosol etc., oral preparation of the present invention can be liquid, suspendible, the form that the grade of dry powder is conventional, most preferably buccal bioadhesive tablet, buccal tablet.Its preparation is prepared according to galenic pharmacy routine techniques, preferred preparation method as:.
The preparation of mouth ulcer lozenge:
Buccal tablet of the present invention is processed by following composition and medicine acceptable carrier and is prepared from:
Glucosamine, binding agent, correctives, fluidizer, lubricant, above supplementary material, 1000 tablets of tablets made by mixing granulation tabletting.
The preparation of collutory
1. prescription composition forms with preparation: glucosamine, distilled water is appropriate.2. prepare: get glucosamine and be surely dissolved in appropriate hot distilled water, cooled and filtered, on filter, adding distil water is to 1000ml.
The preparation of patch:
Preparation method 1: macerated by PVA adding distil water, in a water bath heating for dissolving, make it expand, placement is spent the night, and makes rubber cement.Get glucosamine to pulverize, cross 180 mesh sieves, add in liquid, mix well gently.Leave standstill removing bubble, incline to and sterilize in advance and scribble on the glass plate of liquid paraffin, paint the uniform membrane of thickness, put (70-80 DEG C) drying, skinning in baking box, be cut into suitable size diaphragm, packaging.
Preparation method 2, by the PVA of commercially available commercial size more than 85% soak with ethanol 24h, is filtered, is pressed dry, then soaks 1 time, is filtered dry.Get the PVA processed and add appropriate distilled water, place and make a night it fully swelling, in the water-bath of putting 100 DEG C, heated and stirred is to fully dissolving, and filters for subsequent use; With legal system for PVA rubber cement liquid, glycerol adding 1ml, stirs, and adds water to enough, and insulation 10 ~ 20min in the water-bath of putting about 50 DEG C, removing bubble is for subsequent use.Separately be dissolved in appropriate distilled water by glucosamine, be dissolved in by cleum jecoris piscis concentratum in glycerol, to merge after two liquid slowly in impouring PVA rubber cement liquid, limit edged stirs and adds water to enough, and blank PVA rubber cement liquid removes bubble with method.Be applied to equably on the glass plate of sterilizing by this rubber cement liquid, rete is about 0.3mm, to put in drying baker after less than 60 DEG C dryings, not pastille PVA rubber cement liquid is coated with again, thick about 0.2mm, with the dry rear demoulding of method on film, to sterilize 1h with ultra violet lamp, draw lattice area as required, pack and get final product.
The preparation of paste:
(1) be first dissolved in by ethyl hydroxybenzoate in appropriate hot distilled water, (2) PVA-124 adds in appropriate hot distilled water, stirs evenly, puts in water-bath and heat peptization.(3) MC expands with appropriate cold distilled water and dissolves.(4) a small amount of 95% dissolve with ethanol of glucosamine, adds in glycerol and stirs evenly.(5) starch adds in appropriate distilled water, heating in water bath gelatinizing, (2) is added while hot and stirs evenly, and add (3) after slightly cold, (4) stir evenly, adding distil water, to full dose, stirs evenly, subpackage and get final product.
Compositions of the present invention, its formula is through screening and obtains, present invention employs different formula and compare screening, have found most preferred formula and formula of the present invention, the formula of the existing preparation of this recipe ratio have many advantages as good in: mouthfeel, do not stimulate, rapid-action, consumption is few, safety non-toxic easy to use.
Pharmaceutical composition of the present invention is in use according to the situation determination usage and dosage of patient.
Below by way of test data, beneficial effect of the present invention is described:
The experimentation of glucosamine being carried out to anti-experimental character oral ulcer is as follows.
Materials and methods
Material animal: SD rat 40, female, body weight 180 ~ 220g.Medicine and reagent: the suspension that glucosamine is made into, BINGPENG SAN,
Experimental technique
Set up experimental Oral ulcer model, get SD rat 40, be the glass tubing of 2mm with bottom diameter, built-in cotton pellet, make to put down with glass end opening bottom cotton pellet, then in pipe, instillation 90% carbolic acid solution, to just soaking into cotton pellet, is then placed on inside the lower lip of rat oral cavity and cheek mucosa burns 45s, be partially formed oral ulcer after 24h.
To the treatment of experimental oral ulcer rat with observe the basic, normal, high dosage group of suspension modeling rat being divided at random glucosamine and being made into, positive and model control group.To basic, normal, high dosage, be respectively 1g, 5g, 10g.The medicinal BINGPENG SAN of positive control, dosage is 0.25g/.I.e. administration after each group of modeling, after administration, every day observes the recovery situation in rat ulcer face, gets blood after administration 3d after eyeball, the anticoagulant heparin pipe that instillation is dried, for numeration of leukocyte.Successive administration, after 12 days, puts to death rat, takes its body weight, spleen weighs and chest gland weight, calculates spleen and thymus index.
Result: the suspension that glucosamine is made on oral cavity ulcer rat ordinary circumstance and oral ulcer healing days affect modeling success after, the activity of each group rat and food-intake are all than previously reducing to some extent.Continuous Observation 5 days after administration, activity and the food-intake of the suspension administration group that glucosamine is made into have obvious recovery compared with before administration, and the recovery situation of model group rats is obviously not as good as administration group.The 8th day upon administration, in each administration group, all have ulcer healing animal to occur, and model group rats began have healing animal to occur in the 11st day.
Glucosamine hydrochloride is to the therapeutic effect of 9 subject oral cavity ulcer:
Subjects: experimenter is totally 9 people, wherein male 4 people, women 5 people, all suffers from a place and above oral ulcer.
Test medication: glucosamine hydrochloride powder
Test method: after patient gargles, is applied to skin surface, every day 3-5 time by glucosamine hydrochloride powder 0.2g.3 days observation periods.
Evaluation criterion:
Effective: ulcer heals completely
Effective: after treatment, congestion and swelling pain alleviates, and ulcer surface reduces
Invalid: after treatment, congestion and swelling pain alleviates, and ulcer surface does not reduce
Result of the test:
In 3 days all effectively (9 people, 13 place's ulcer), belong to and heal completely, healing rate reaches 100% to all ulcer.
The present invention, according to modern pharmaceutical technique, aims at oral ulcer patient design.According to there being following advantage: mouthfeel is good, do not stimulate, rapid-action, consumption is few, safety non-toxic easy to use, the drug-induced drug resistance of antibiotic-free class, not containing hormone, without side effect, use pad pasting of the present invention, ulcer surface can not only be made to heal, reduce recurrence, and can effectively prevent gingival swelling and pain, angular cheilitis, pharyngitis, toothache etc.To above-mentioned disease once produce, use product of the present invention can effective mitigation symptoms.
Compositions of the present invention is effective to oral diseases such as the various oral ulcer such as red aphtha, whitish aphthae and laryngopharynx swelling and pain, sprays a little or is coated on affected part, within 1-3 days, can fully recover with this medicine, thus solves the difficult problem that oral ulcer disease is for a long time difficult to cure.
Detailed description of the invention:
By following specific embodiment, the invention will be further described, but not as limitation of the present invention.
Embodiment 1, buccal tablet
Glucosamine hydrochloride 100g, carboxymethyl cellulose 20g, steviol glycosides 50g, micropowder silica gel 10g.Get above supplementary material, mixing, granulate, 1000 tablets of tablets made by tabletting.
Embodiment 2, paste
(1) be first dissolved in by ethyl hydroxybenzoate in appropriate hot distilled water, (2) PVA-124 adds in appropriate hot distilled water, stirs evenly, puts in water-bath and heat peptization.(3) MC expands with appropriate cold distilled water and dissolves.(4) a small amount of 95% dissolve with ethanol of glucosamine sulfate, adds in glycerol and stirs evenly.(5) starch adds in appropriate distilled water, heating in water bath gelatinizing, (2) is added while hot and stirs evenly, and add (3) after slightly cold, (4) stir evenly, adding distil water, to full dose, stirs evenly, subpackage and get final product.
Claims (2)
1. the application of glucosamine hydrochloride in the medicine of preparation treatment oral ulcer, wherein said medicine is the buccal bioadhesive tablet that local uses, buccal tablet, collutory, paste, spray, and wherein the effective dose of glucosamine hydrochloride treatment oral ulcer is 0.1-0.5g.
2. application according to claim 1, is characterized in that, wherein the effective dose of glucosamine hydrochloride treatment oral ulcer is 0.2g.
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| CN201010601958.8A CN102058608B (en) | 2010-12-17 | 2010-12-17 | New application of glucosamine in treating dental ulcer |
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| CN102058608B true CN102058608B (en) | 2014-12-17 |
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| RU2542469C1 (en) * | 2014-02-25 | 2015-02-20 | Сергей Владимирович Сирак | Agent for local therapy of recurrent oral aphthae accompanying dental stomatitis and periodontitis |
| CN112385838B (en) * | 2019-10-16 | 2022-11-08 | 富诺健康股份有限公司 | Food containing anthocyanin and preparation method thereof |
| CN114191405B (en) * | 2021-11-06 | 2023-02-03 | 山东润德生物科技有限公司 | Preparation method and application of gel type glucosamine preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1470244A (en) * | 2002-07-22 | 2004-01-28 | 中国人民解放军第三军医大学 | Application of N-acetyl-D-glucosamine in the preparation of skin and mucous membrane microecological balance regulator medicine |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1470244A (en) * | 2002-07-22 | 2004-01-28 | 中国人民解放军第三军医大学 | Application of N-acetyl-D-glucosamine in the preparation of skin and mucous membrane microecological balance regulator medicine |
Non-Patent Citations (2)
| Title |
|---|
| 氨基葡萄糖抗炎功能的研究;杨艳等;《华东六省一市生物化学与分子生物学会2008年学术交流会议论文摘要汇编》;20080801;328 * |
| 福建省卫生厅医政处.口腔粘膜病.《常见病临床诊治常规(第三册)》.2001,(第1版),205-206. * |
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