CN102512420A - Officinal composite using Rebamipide officinal salt as active ingredient - Google Patents
Officinal composite using Rebamipide officinal salt as active ingredient Download PDFInfo
- Publication number
- CN102512420A CN102512420A CN2011103881322A CN201110388132A CN102512420A CN 102512420 A CN102512420 A CN 102512420A CN 2011103881322 A CN2011103881322 A CN 2011103881322A CN 201110388132 A CN201110388132 A CN 201110388132A CN 102512420 A CN102512420 A CN 102512420A
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- Prior art keywords
- rebamipide
- salt
- officinal
- pharmaceutical composition
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229950004535 rebamipide Drugs 0.000 title claims abstract description 81
- ALLWOAVDORUJLA-UHFFFAOYSA-N Rebamipida Chemical compound C=1C(=O)NC2=CC=CC=C2C=1CC(C(=O)O)NC(=O)C1=CC=C(Cl)C=C1 ALLWOAVDORUJLA-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 150000003839 salts Chemical class 0.000 title claims abstract description 31
- 239000004480 active ingredient Substances 0.000 title abstract 2
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- LUPNKHXLFSSUGS-UHFFFAOYSA-M sodium;2,2-dichloroacetate Chemical compound [Na+].[O-]C(=O)C(Cl)Cl LUPNKHXLFSSUGS-UHFFFAOYSA-M 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an officinal composite using a Rebamipide officinal salt as an active ingredient, wherein the officinal salt comprises choline salts, arginine salt, heme-L-lysinate, trometamol salt, sodium salt, calcium salt, zinc salt, magnesium salt and the like. The Rebamipide officinal salt can be combined with a pharmaceutic adjuvant to produce solid preparations, wherein the solid preparations comprise particles, tablets, capsules, chewable tablets, orally distegrating tablets, effervescent tablets, dispersible tablets, sustained-release tablets, sustained-release capsules and the like; the Rebamipide officinal salt also can be combined with the pharmaceutic adjuvant to produce liquid preparations, wherein the liquid preparations comprise eye drops and the like; and the Rebamipide officinal salt is used for treating peptic ulcer and dry eye syndrome.
Description
Technical field
The present invention is the Pharmaceutical composition of active component for a kind of pharmaceutical salts with rebamipide, belongs to medical technical field.
Background technology
PUD comprises gastric duodenal ulcer, is clinical common disease.Sickness rate at Chinese peptic ulcer improves (more than 10%) year by year, and some areas have had a strong impact on patient's quality of life up to 13-28%.The medicine of present treatment peptic ulcer mainly contains proton pump inhibitor and the H2 receptor is picked up anti-agent; These medicines all are to improve the various symptoms that ulcer causes rapidly through strong gastric acid inhibitory secretion; But because effect is very fast; So have ulcer to be prone to the problem of recurrence, the back 1 year relapse rate that heals is up to 60-70%.Nineteen ninety, Tarna wski at first proposes the notion of ulcer healing quality, thinks that the healing of peptic ulcer should only not paid close attention to ulcer healing speed, more should pay attention to the ulcer healing quality, i.e. really healing fully of ulcer from the gastric mucosa 26S Proteasome Structure and Function.Focus on the aggressive factor of minimizing gastric mucosa at present clinically for the treatment of peptic ulcer,, just causing clinicist's attention and be directed against the treatment of strengthening the gastric mucosa reparation as according to helicobacter pylori and gastric acid inhibitory secretion.
It is different with proton pump inhibitor antiulcer mechanism that rebamipide and H2 receptor are picked up anti-agent; Mainly be to synthesize and links such as gastric mucus secretion, removing oxygen-derived free radicals through increase gastric mucosal blood flow, PGE2; The improvement of facilitating digestion road ulcer healing and inflammation; Reduce ulcer recurrence, and can improve eradication rate helicobacter pylori.Not only gastritis, gastric ulcer are had good efficacy, and can alleviate NSAIDs, the microbial gastric mucosa injury of helicobacter pylorus.Rebamipide has become the first-selected medication of gastric mucosal protection at present, and supply falls short of demand for product.Rebamipide listing at present have only tablet and capsule because its soluble,very slightly in ethanol or methanol is insoluble in water,, and have certain restriction for the exploitation of rebamipide liquid preparation so its oral bioavailability is had certain influence.
Summary of the invention
The present invention is the Pharmaceutical composition of active component for a kind of pharmaceutical salts with rebamipide, and wherein pharmaceutical salts comprises: choline salt, arginine salt, lysinate, amino butanetriol salt, sodium salt, calcium salt, zinc salt, magnesium salt etc.The method for preparing of its pharmaceutical salts is seen embodiment
The pharmaceutical salts of rebamipide of the present invention can be processed solid preparation with the pharmaceutic adjuvant combination; Comprise granule, tablet, capsule, chewable tablet, oral cavity disintegration tablet, effervescent tablet, dispersible tablet, slow releasing tablet, slow releasing capsule etc.; Wherein the unit consumption of the pharmaceutical salts of rebamipide is (in rebamipide) 25-400mg; Preferred 100mg can be used for the treatment of peptic ulcer.The pharmaceutical salts of rebamipide also can be processed liquid preparation with the pharmaceutic adjuvant combination, comprises eye drop etc.; Wherein the concentration of the pharmaceutical salts of rebamipide is (in rebamipide) every 100ml: 0.2-10g, preferred 100ml: 2g; Be used for the treatment of xerophthalmia.
The present invention is the Pharmaceutical composition of active component for a kind of pharmaceutical salts with rebamipide, and the pharmaceutical salts of rebamipide can be processed solid preparation and ophthalmic preparation with suitable adjuvant.
The example of the adjuvant that solid preparation can use comprises: excipient, and lubricant, disintegrating agent, binding agent, surfactant, plasticizer, acidic flavoring agent, sweeting agent etc. are applicable to the carrier of this area.
The concrete example of excipient comprises crystalline cellulose, potato starch, dextrin, corn starch, lactose, sucrose, mannitol, Pulvis Talci, calcium carbonate etc.The concrete example of lubricant comprises magnesium stearate, stearic acid etc.The concrete example of disintegrating agent comprises carboxymethyl starch sodium, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone etc.The concrete example of binding agent comprises arabic gum, hydroxypropyl cellulose, gelatin, polyvinylpyrrolidone, polyvinyl alcohol etc.The concrete example of surfactant comprises sodium lauryl sulphate etc.The concrete example of plasticizer comprises oils such as polyoxyethylene sorbitan monoleate, oil with hydrogenated soybean, castor oil hydrogenated, hydrogenated tallow; Brazil wax, wax classes such as Cera Flava; Higher hydrocarbons such as paraffin, ceresine, microwax; Perhaps their mixture.The concrete example of acidic flavoring agent comprises acidic flavoring agent such as ascorbic acid, tartaric acid, L-arginine, malic acid.The concrete example of sweeting agent comprises sucralose, be selected from by form at least a of thaumatin, Folium Stevlae Rebaudianae and Fructus Momordicae extract and as sweeting agent.
The adjuvant example that ophthalmic preparation can use comprises: emulsion stabilizer, metal salt compound, PH regulator, antiseptic, surfactant etc.
The concrete example of emulsion stabilizer comprises polyvinyl alcohol; Metal salt compound comprises the water-soluble metal salt compound that medically is fit to, and concrete example comprises sodium chloride, potassium chloride, sodium dihydrogen phosphate, sodium succinate, Soluble tartar., sodium tartrate, sodium hydroxide, calcium chloride, magnesium chloride, magnesium hydroxide, calcium hydroxide, calcium carbonate etc.The concrete example of PH regulator comprises citric acid, hydrochloric acid, phosphoric acid, acetic acid etc.The concrete example of antiseptic comprises methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, edetate sodium etc.The concrete example of surfactant comprises sodium lauryl sulphate etc.
The specific embodiment
Embodiment 1:: rebamipide choline salt
With rebamipide and choline solution is raw material, at first rebamipide is dissolved in the alcoholic solution, and to wherein adding 1.5 normal choline solutions, room temperature stirred 1-3 hour down then, and through filtering, drying obtains product rebamipide choline salt.
Embodiment 2:: rebamipide amino butanetriol salt
With rebamipide and trometamol is raw material, at first rebamipide is dissolved in the alcoholic solution, then to wherein adding the normal trometamol of 1-1.1; Room temperature stirred 1-3 hour down, add activated carbon decolorizing after, through filtering; Drying obtains product rebamipide amino butanetriol salt.
Embodiment 3: the rebamipide arginine salt
With rebamipide and arginine is raw material, and rebamipide is dissolved in the methanol solution, adds the normal arginine powder of 1-1.1, room temperature reaction, and through filtering, drying process obtains product rebamipide arginine salt.
Embodiment 4: the rebamipide lysinate
With rebamipide and lysine is raw material; Rebamipide is dissolved in the methanol solution; Add the normal dl-lysine solution of 1-1.5 (mass percentage concentration is 25%～30%), room temperature reaction is cooled to 10 ℃ with interior crystallize; Through filtering, drying process obtains product rebamipide lysinate again.
Embodiment 5: the rebamipide sodium salt
At first rebamipide is dissolved in the methanol, adds the NaOH aqueous solution of 1M, the equivalent proportion that makes rebamipide and NaOH is 1: 1.5, and 5-10 ℃ is reacted to the raw material complete obiteration, and through filtering, drying obtains product rebamipide sodium salt.
Embodiment 6: the rebamipide calcium salt
At first rebamipide is dissolved in the methanol, adds 1.5 normal solid CaO, after the complete obiteration of room temperature reaction to raw material, through filtering, drying obtains product rebamipide calcium salt.
Embodiment 7:: rebamipide zinc salt
At first rebamipide is dissolved in the methanol, adds 1.5 normal solid ZnO, after the complete obiteration of room temperature reaction to raw material, through filtering, drying obtains product rebamipide zinc salt.
Embodiment 8: the rebamipide magnesium salt
At first rebamipide is dissolved in the methanol, adds 1.5 normal solid MgO, after the complete obiteration of room temperature reaction to raw material, through filtering, drying obtains product rebamipide sodium salt.
Embodiment 9: the preparation of dry suspension
Method for preparing:
1. each supplementary material pulverize separately of writing out a prescription is crossed 100 orders, and is subsequent use,
2. with the abundant mix homogeneously of each supplementary material, packing gets final product.
Embodiment 10: the preparation of granule
| The rebamipide sodium salt | 100 | 100 | 100 |
| Lactose | 185 | 185 | 185 |
| Polyvinylpyrrolidone | 15 | 15 | 15 |
| Water | In right amount | In right amount | In right amount |
| Sucrose | 68 | 68 | 68 |
| Mannitol | 15 | 15 | 15 |
| Sucralose | 5 | 5 | 5 |
Method for preparing:
1. each supplementary material of recipe quantity joins in the wet mixing pelletizer mixing and stirring.
2. add purified water and in right amount above mixture is mediated, granulate, dry packing gets final product.
Embodiment 11: the preparation of tablet
| The rebamipide choline salt | 100 | 100 | 100 |
| Lactose | 185 | 185 | 185 |
| Corn starch | 51 | 51 | 51 |
| Carboxymethyl starch sodium | 15 | 15 | 15 |
| Cross-linking sodium carboxymethyl cellulose | 9 | 9 | 9 |
| Water | In right amount | In right amount | In right amount |
| Dextrin | 68 | 68 | 68 |
| Polyoxyethylene sorbitan monoleate | 2 | 2 | 2 |
| Magnesium stearate | 10 | 10 | 10 |
1. recipe quantity rebamipide choline salt, lactose, corn starch, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, dextrin, polyoxyethylene sorbitan monoleate, acidic flavoring agent and sweeting agent join in the wet mixing pelletizer, mixing and stirring.
2. add purified water and in right amount above mixture is mediated, utilize the screen cloth extrusion granulator machine in 0.6 micron in aperture is housed, the mixture that obtains is granulated, utilize spheroidal particle to process sphere then.
3. the dry granule that obtains, collection has 0.355～1mm size particles as nuclear particle.To contain the mixture of 100g ethanol and 36g water, add an amount of mannitol, stirring makes it suspendible and obtains coating solution.
4. above-mentioned nuclear particle is put in the fluidised bed granulator, intake air temperature 50 degree are regulated feed liquor speed 20g/ minute, spray coating solution to the surface of nuclear particle.
5. behind the coating,, carry out granulate with 1180 microns screen clothes with granule 50 degree oven dry.
6. the recipe quantity magnesium stearate is joined in the above-mentioned granule mix homogeneously, tabletting.
Embodiment 12: the preparation of capsule
The granule of embodiment 10 gained is encapsulated, promptly get.
Embodiment 13: eye is with the preparation of agent
| Rebamipide (rebamipide choline salt) | ?100 |
| The polyvinyl alcohol of partial hydrolysis | ?1000 |
| Sodium citrate | ?146 |
| Propyl p-hydroxybenzoate | ?15 |
| Methyl parahydroxybenzoate | ?60 |
| Edetate sodium | ?50 |
| Sodium chloride | ?715 |
| Potassium chloride | ?180 |
| Sodium hydroxide | (with adjustment PH to 6) in right amount |
| Hydrochloric acid | (with adjustment PH to 6) in right amount |
| Purified water | In right amount |
| Total amount | ?100L |
Method for preparing:
1. recipe quantity rebamipide stirring and dissolving is sterilized in the polyvinyl alcohol of partial hydrolysis;
2. residue antiseptic, PH regulator, metallic compound heating for dissolving are filtered through sterilizing filter in purified water;
3. above-mentioned rebamipide through disinfecting action is joined in the filtrate, stir with magnetic stirrer through mixture and obtain aqueous suspension;
Above-mentioned aqueous suspension thing is aseptic subpackaged in the 5-15ml plastic bottle 4., promptly get.
Embodiment 14: the rebamipide pharmaceutical salts is to the experiment of gastric ulcer mice gastric mucosal protective effect
Experimental technique:
40 of cleaning level Male Kunming strain mice, body weight 18g～22g is divided into 4 groups at random: ethanol ulcer model group; The rebamipide group; Rebamipide choline salt group, rebamipide sodium salt group, 10 every group.
Ethanol ulcer model group: the mice drinking-water of normally taking food, irritate stomach give 0.85% sodium chloride solution 0.2ml/ only/day, continuous 5 days.
The 6th day, mice freely drank water, behind the fasting 24h, irritate stomach give dehydrated alcohol (1ml/ only) after 1 hour the cervical vertebra dislocation put to death mice.
Each treatment group: the mice drinking-water of normally taking food, irritate stomach give corresponding rebamipide class medicine 0.2ml/ only/day, continuous 5 days.The 6th day, mice freely drank water, behind the fasting 24h, irritate stomach give dehydrated alcohol (1ml/ only) after 1 hour the cervical vertebra dislocation put to death mice.More than each group mice is cut open the belly, the ligation pyloric part, 1% neutral formalin solution 1ml irritates stomach, the ligation pars cardiaca, free stomach, and after putting 10% neutral formalin solution 10min, cutting off along greater gastric curvature, 0.85% sodium chloride solution washes away content, flattening.The only light microscopic histology's variation of observation gastric mucosa down of normal control group.All the other each set of calculated UI and suppression ratio, and light microscopic is observed the histologyization of gastric mucosa down.Ulcer inhibition rate: (averaging model group-average experimental group)/averaging model group UI.Experimental result: compare with ethanol damage ulcer model, rebamipide and pharmaceutical salts thereof all can obviously suppress ethanol to the mice gastric mucosal damage, and the pharmaceutical salts effect of rebamipide is more remarkable.
Table 1 rebamipide pharmaceutical salts causes the influence of gastric mucosa injury mice UI and suppression ratio to ethanol
| Group | UI | Suppression ratio (%) |
| Ethanol ulcer model group | 42.45±9.56 | |
| The rebamipide group | 19.54±6.54 | 54.0 |
| Rebamipide choline salt group | 12.34±5.49 | 70.9 |
| Rebamipide sodium salt group | 11.65±6.04 | 72.6 |
Mice gastric mucosa injury and mucosa tissue are observed:
Ethanol causes mice gastric mucosa injury light microscopic finding: the mucous layer layer of structure is clear, and epithelium is imperfect, and local gland structure is disorderly, and the many places band shape is damaged, and deep lamina propria and tela submucosa have than multi-lymphocytes.And under the rebamipide pharmaceutical salts administration group mice gastric mucosa light microscopic: epithelium is imperfect, and it is more neat that body of gland is arranged, a small amount of exfoliative cyte fragment in the lumen of gland, the visible a small amount of lymphocyte in lamina propria deep.
Embodiment 15: the rebamipide pharmaceutical salts is to the experiment of the therapeutical effect of xerophthalmia
Experimental technique: 40 of purebred NZws, body weight 2.5～3.0kg, 4～May of age; Eyes drip Gernebcin eye drops before the art, and after continuous 3 times, choosing right eye is experimental eye; Operation is taken except that rabbit right eye lachrymal gland, behind Harder gland and the instant embrane, smears apart from bulbar conjunctiva beyond the limbus of corneae 3mm with 50% trichloroacetic acid; Process the rabbit dry eye model, begin in the 3rd week of postoperative to observe, 40 rabbits are divided into the blank group at random; The rebamipide group; Rebamipide choline salt group, rebamipide sodium salt group, 10 every group.The treatment group is with rebamipide and various pharmaceutical salts, and the blank group is used the artificial tears, respectively local eye dripping treatment rabbit model xerophthalmia; Put drops in one's eyes 3 times/day; 2/inferior,, check 1 time weekly and suffer from the wet length of canthus conjunctiva Schirmerl test 5 weeks of logotype; Breakup time of tear film and brave red colouring situation are estimated curative effect.
Experimental result: rabbit model trouble eye wet length of Schirmerl test and the brave red colored spots number average of angle conjunctiva are significantly improved than matched group after 3 weeks of observation group's treatment and 6 weeks, and the therapeutical effect of rebamipide pharmaceutical salts is more remarkable.See table 1 and table 2.
Two groups of rabbits of table 1 treatment different times suffer from the red painted comparison of counting (
is individual) of the average tiger of eye
| Group | 0 week | 3 weeks | 6 weeks |
| Artificial tears's matched group | 76.58±9.54 | 59.76±5.44 | 42.68±6.24 |
| The rebamipide group | 75.58±4.59 | 41.56±4.76 | 33.45±3.46 |
| Rebamipide choline salt group | 75.54±6.14 | 34.42±7.26 | 21.55±4.10 |
| Rebamipide sodium salt group | 17.84±5.89 | 35.68±6.01 | 19.72±5.11 |
Table 2 a liang group rabbit suffers from schirmerl experiment wet long relatively (
mm)
| Group | 0 week | 3 weeks | 6 weeks |
| Artificial tears's matched group | 5.84±0.68 | 8.56±0.61 | 10.01±0.56 |
| The rebamipide group | 5.69±0.71 | 13.48±0.71 | 15.64±0.49 |
| Rebamipide choline salt group | 5.85±0.64 | 17.49±0.55 | 20.64±0.81 |
| Rebamipide sodium salt group | 5.73±0.59 | 16.58±0.49 | 19.69±0.62 |
Claims (7)
1. the pharmaceutical salts with rebamipide is the Pharmaceutical composition of active component, it is characterized in that pharmaceutical salts comprises: choline salt, arginine salt, lysinate, amino butanetriol salt, sodium salt, calcium salt, zinc salt, magnesium salt etc.
2. the described Pharmaceutical composition of claim 1 is characterized in that, the pharmaceutical salts of rebamipide can be processed solid preparation with the pharmaceutic adjuvant combination, comprises granule, tablet, capsule, chewable tablet, oral cavity disintegration tablet, effervescent tablet, dispersible tablet, slow releasing tablet, slow releasing capsule etc.
3. the described Pharmaceutical composition of claim 1 is characterized in that, the pharmaceutical salts of rebamipide can be processed liquid preparation with the pharmaceutic adjuvant combination, comprises eye drop etc.
4. the described Pharmaceutical composition of claim 2 is characterized in that, the unit consumption of the pharmaceutical salts of rebamipide is (in rebamipide) 25-400mg, preferred 100mg.
5. the described Pharmaceutical composition of claim 3 is characterized in that, the concentration of the pharmaceutical salts of rebamipide is (in rebamipide) every 100ml: 0.2-10g, preferred 100ml: 2g.
6. the described Pharmaceutical composition of claim 2 is used for the purposes of digestive ulcer medicament in preparation.
7. the described Pharmaceutical composition of claim 3 is used for the purposes of xerophthalmia medicine in preparation.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103881322A CN102512420A (en) | 2011-11-29 | 2011-11-29 | Officinal composite using Rebamipide officinal salt as active ingredient |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103881322A CN102512420A (en) | 2011-11-29 | 2011-11-29 | Officinal composite using Rebamipide officinal salt as active ingredient |
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|---|---|
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|---|---|---|---|
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103360354A (en) * | 2012-12-04 | 2013-10-23 | 广东中科药物研究有限公司 | New compound for preparation of eye drops |
| WO2014051163A1 (en) * | 2012-09-28 | 2014-04-03 | Otsuka Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising rebamipide |
| CN105012267A (en) * | 2015-08-19 | 2015-11-04 | 海南科进生物制药有限公司 | Rebamipide tablet and preparation method thereof |
| CN108136036A (en) * | 2015-10-01 | 2018-06-08 | 三进制药株式会社 | Novel ophthalmic composition comprising Rebamipide and preparation method thereof |
| CN108815175A (en) * | 2018-04-26 | 2018-11-16 | 北京蓝丹医药科技有限公司 | A kind of spray that eye is applied outside |
| CN112603899A (en) * | 2020-12-23 | 2021-04-06 | 南京友杰医药科技有限公司 | Rebamipide enteric-coated tablet and preparation method thereof |
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2011
- 2011-11-29 CN CN2011103881322A patent/CN102512420A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2014051163A1 (en) * | 2012-09-28 | 2014-04-03 | Otsuka Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising rebamipide |
| CN103360354A (en) * | 2012-12-04 | 2013-10-23 | 广东中科药物研究有限公司 | New compound for preparation of eye drops |
| CN105012267A (en) * | 2015-08-19 | 2015-11-04 | 海南科进生物制药有限公司 | Rebamipide tablet and preparation method thereof |
| CN108136036A (en) * | 2015-10-01 | 2018-06-08 | 三进制药株式会社 | Novel ophthalmic composition comprising Rebamipide and preparation method thereof |
| EP3355929A4 (en) * | 2015-10-01 | 2019-06-19 | Samjin Pharmaceutical Co., Ltd. | Novel ophthalmic composition comprising rebamipide and method for preparing the same |
| US10918725B2 (en) | 2015-10-01 | 2021-02-16 | Samjin Pharmaceutical Co., Ltd. | Ophthalmic composition comprising rebamipide and method for preparing the same |
| CN108815175A (en) * | 2018-04-26 | 2018-11-16 | 北京蓝丹医药科技有限公司 | A kind of spray that eye is applied outside |
| CN112603899A (en) * | 2020-12-23 | 2021-04-06 | 南京友杰医药科技有限公司 | Rebamipide enteric-coated tablet and preparation method thereof |
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Application publication date: 20120627 |