CN102379869A - Oral preparation containing saxagliptin and application thereof - Google Patents
Oral preparation containing saxagliptin and application thereof Download PDFInfo
- Publication number
- CN102379869A CN102379869A CN2010102671750A CN201010267175A CN102379869A CN 102379869 A CN102379869 A CN 102379869A CN 2010102671750 A CN2010102671750 A CN 2010102671750A CN 201010267175 A CN201010267175 A CN 201010267175A CN 102379869 A CN102379869 A CN 102379869A
- Authority
- CN
- China
- Prior art keywords
- sha gelieting
- pharmaceutically acceptable
- granule
- tablet
- gelieting
- 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.)
- Pending
Links
Abstract
The invention relates to a novel oral preparation, which consists of saxagliptin of 1swung dash40mg or pharmaceutically acceptable salt and carriers thereof, wherein the oral preparation is a tablet, a capsula, a dispersible tablet, a chewable tablet, a pill, granular formulation, a dry suspension, an orally disintegrating tablet, a soft capsule, a buccal tablet, an effervescent tablet, an oral solution, an oral suspension, a drop, a sustained release preparation or a controlled release preparation, and is used for treating diabetes mellitus or related diseases. Compared with the common tablets, the dispersible tablet has the characteristics of quick and uniform dispersing, short disintegrating time, quick medicine digestion, high bioavailability, fewer adverse effects and convenience in medicine taking.
Description
Technical field
The present invention relates to a kind of novel oral formulations, it is made up of the Sha Gelieting of 1～40mg or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier, is used to treat diabetes or relevant disease, belongs to medical technical field.
Background technology
Diabetes are a kind of common incretion metabolism diseases; Along with the change of life style and the acceleration of aging process; The prevalence of China's diabetes is being fast rise trend, becomes the important Chronic Non-Communicable Diseases of another serious harm people ' s health after cardiovascular and cerebrovascular disease, tumor.Its acute and chronic complication, especially the chronic disease complication is involved a plurality of organs, disables, fatality rate is high, has a strong impact on patient's physical and mental health, and brings white elephant (non-patent literature) for individual, family and society.
According to the suggestion of The World Health Organization (WHO) and expert group of IDF (IDF), diabetes can be divided into 4 kinds of I type, II type, other specific types and gestational diabetes.In recent years; Raising along with countries in the world The development in society and economy and resident living level; The sickness rate and the prevalence of diabetes raise year by year, become the great social problem that threatens people ' s health, cause national governments, hygiene department and numerous medical personnels' concern and attention.
Diabetes also are a kind of global epidemic diseases, and its prevalence increases day by day, and according to the estimation of WHO, the existing diabetics about 1.75 hundred million in the whole world will reach 300,000,000 to 2025 at present.China's diabetes prevalence is also sharply increasing, and has increased by 4～5 times from the eighties to the mid-90 in 20th century, estimates existing at present diabetics three or four thousand ten thousand.Think that in the past diabetes are diseases of person in middle and old age.Discovered in recent years, no matter in the west or China, along with increasing of child and teenager obesity, child and teen-age diabetes, particularly the type 2 diabetes mellitus number of patients also increases rapidly, has become the early stage big health problem of life.Therefore, the safe and effective antidiabetic medicine of development of new has become the problem that various countries press for solution.
Sha Gelieting or its pharmaceutically acceptable salt belong to one type of brand-new breakthrough innovation medicine-dipeptidyl peptidase-4 (DPP-4) inhibitor.It can improve the physiological mechanism of a kind of being called as " intestinal insulinotropic hormone ", regulates glucose level through the β cell and the α cell that influence in the pancreas.Have only when the β cell dysfunction to occur and cause that insulin level reduces or, when making glycogen produce uncontrolled increase, just can work through the inhibition dipeptidyl peptidase when α cell and β cell generation dysfunction.
Patent documentation 1～2 discloses provides the chemical compound that suppresses DPP IV (DP4).The method of treatment diabetes and relevant disease also is provided; Especially type ii diabetes and other diseases in this general introduction, this method are used the for example combination of metformin, glibenclamide, troglitazone, pioglitazone, Rui Gelie ketone and/or insulin and/or one or more hypolipidemics and/or anti-obesity medicine and/or other medicine of such DP4 inhibitor or such DP4 inhibitor and one or more another kind of antidiabetic drugs.
Patent documentation 3 discloses provides the physics of said chemical compound crystal structure: Sha Gelieting, comprises its free alkali monohydrate (H-1 form) and hydrochlorate thereof, comprises and contains 0.75 equivalent H
2The hydrochlorate of O (H0.75-3 form) and contain 2 equivalent H
2The hydrochlorate of O (H2-1 form) and hydrochlorate P-5 pattern preferably are pure basically form, and other forms as described herein; The pharmaceutical composition that contains compound I or IA structure, this preparation of drug combination method, employed intermediate in its preparation, and the method for using these structure treatment such as diseases such as diabetes.
Patent documentation 4 discloses coated tablet formulation; It comprises medicine for example DPP4-inhibitor saxaglipitin or its HCl salt that intramolecular cyclization be prone to take place; Said preparation comprises the label and other conventional excipients that contains one or more filleies; This label comprises the two-layer or multiwalled coating that comprises that encapsulates above that; The serve as reasons interior sealing coatings of one or more coating polymer formation of one deck at least wherein, wherein the second layer is by medicine (DPP4-inhibitor) and one or more coating polymer formation, and can select the 3rd external protection by one or more coating polymer formation that can not select for use but preferably select for use for use.The present invention also is provided for forming the method for coated tablet.
Patent documentation 5 discloses and has been used to produce method and the chemical compound based on the inhibitors of dipeptidyl IV of cyclopropyl-condensed pyrrolidine.
Oral formulations of the present invention, administration every day 1～2 time is preferably once a day, and the patient is very easy to use like this, has improved the compliance that the patient takes medicine, and improves patient's quality of life.
Non-patent literature: Ministry of Public Health Department of Disease Control, diabetology branch of Chinese Medical Association. Chinese diabetes control guide .2008,1-63
Patent documentation 1: Chinese patent CN1427826 (A)
Patent documentation 2: European patent EP 1261586 (B1)
Patent documentation 3: Chinese patent CN101687793 (A)
Patent documentation 4: Chinese patent CN1988891 (A)
Patent documentation 5: Chinese patent CN1791401 (A)
Summary of the invention
The oral formulations that the object of the present invention is to provide a kind of Sha Gelieting or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier by 1～40mg to form, wherein said oral formulations is tablet, capsule, dispersible tablet, chewable tablet, drop pill, granule, dry suspension, oral cavity disintegration tablet, soft capsule, buccal tablet, effervescent tablet, oral solution, oral suspensions, drop, slow releasing preparation or controlled release preparation.
Another object of the present invention also is to provide above-mentioned oral formulations to be used for treating the application of the medicine of diabetes or relevant disease in preparation.
The technical scheme that the present invention solves is following:
(1) a kind of oral formulations of treating diabetes or relevant disease is characterized in that, it is made up of the Sha Gelieting of 1～40mg or its pharmaceutically acceptable salt and at least a pharmaceutically acceptable carrier.
Diabetes of the present invention or relevant disease are type ii diabetes, type i diabetes, impaired glucose tolerance, obesity, hyperglycemia, X syndrome, dysbolismus syndrome, diabetic complication or hyperinsulinemia; Be preferably type ii diabetes, obesity, X syndrome, dysbolismus syndrome or diabetic complication; More preferably type ii diabetes, obesity or diabetic complication.Symptom, disease and disease that set is referred to as " diabetic complication " comprise that retinopathy, neuropathy, nephropathy change, vascular complication, cerebrovascular, osteoarthritis, oral disease and pedopathy become and other known diabetic complications.
Oral formulations of the present invention is tablet, capsule, dispersible tablet, chewable tablet, drop pill, granule, dry suspension, oral cavity disintegration tablet, soft capsule, buccal tablet, effervescent tablet, oral solution, oral suspensions, drop, enteric coated preparation, slow releasing preparation or controlled release preparation; Be preferably tablet, capsule, dispersible tablet, drop pill, granule, dry suspension, oral solution or oral suspensions; More preferably tablet, capsule, dispersible tablet, drop pill, granule or dry suspension.
The Sha Gelieting of 1～40mg of the present invention or its pharmaceutically acceptable salt are preferably: the hydrochlorate of Sha Gelieting; Trifluoroacetate; Hydrobromate; Nitrate; Ammonium sulfate; Tartrate; Fumarate; Benzoate; Mesylate; Benzene sulfonate; Butene dioic acid salt; Tosilate; Maleate; Sulfate; Phosphate; Fumarate; Succinate; Acetate; Malate; Hemifumarate; Citrate; Succinate; Perchlorate; Hydrofluoride; Hydriodate; Ascorbate; Acetate; Lactate; Malonate; Oxalates; Fluoroform sulphonate; Esilate; Glycinate; Lysinate; Arginine salt; Ornithine salt; Glutamate, Glu or aspartate; More preferably: the hydrochlorate of Sha Gelieting, trifluoroacetate, hydrobromate, nitrate, ammonium sulfate, tartrate, fumarate or benzoate; Further be preferably: the hydrochlorate of Sha Gelieting, trifluoroacetate or benzoate most preferably are the Sha Gelieting hydrochlorate.Wherein said 1～40mg is preferably 1～20mg, and more preferably 1～10mg further is preferably about 1.25mg, about 2.5mg, about 5mg or about 10mg.
Wherein said Sha Gelieting or its pharmaceutically acceptable salt can crystallizations, partially crystallizable or amorphous forms, solvate especially hydrate or polycrystalline form exist, also can laevoisomer, dextroisomer, raceme or optical isomer exist.Those that patent documentation CN1427826A, CN1213028C, CN1698601A, CN1791401A, EP1261586 (B1), EP1261586 (A2), US6395767 (B2), WO0168603 (A2), CN1988891A, US7420079 (B2), EP1753406 (A1), EP2137149 (A2), CN101687793 (A), US2005090539 (A1), US2009076118 (A1), WO2008131149 (A2), US2009054303 (A1), WO2005117841 (A1), US2005266080 (A1) are announced are incorporated herein by reference this at this in full.
The chemical name of wherein said Sha Gelieting is (1S; 3S, 5S)-2-[(2S)-2-amino-2-(3-hydroxyl three ring [3.3.1.13,7] last of the ten Heavenly stems-1-yl) acetyl group]-2-azabicyclic-[3.1.0] hexane-3-nitrile monohydrate; English name is saxagliptin, and molecular formula is C
18H
25N
3O
2H
2O, molecular weight are 333.43, and its chemical structural formula is suc as formula shown in (I):
Pharmaceutically acceptable carrier of the present invention is art-recognized; And refer to participate in to deliver or transport any theme composition or its component pharmaceutically acceptable material, component or carrier from the part of part to another organ or the health of an organ or health, like liquid or solid filler, diluent, excipient, solvent or encapsulating material.With theme composition and the compatible meaning of component thereof on, every kind of carrier must be acceptable and be harmless to the patient.Some instances that can be used as the material of pharmaceutically acceptable excipient comprise: (a) saccharide, like lactose, dextrose plus saccharose; (b) starch based is like corn starch and potato starch; (c) cellulose and derivant thereof are like sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (d) pulverous Tragacanth; (e) Fructus Hordei Germinatus; (f) gelatin; (g) Talcum; (h) excipient is like cupu oil and suppository wax; (i) oils is like Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, safflower oil, Oleum sesami, olive oil, Semen Maydis oil and soybean oil; (j) glycols is like propylene glycol; (k) polyalcohols is like glycerol, Sorbitol, mannitol and Polyethylene Glycol; (l) esters is like ethyl oleate and ethyl laurate; (m) agar; (n) buffer agent class is like magnesium hydroxide and aluminium hydroxide; (o) alginic acid; (p) pyrogen-free water; (q) isotonic saline solution; (r) fluid used of intravenous includes but not limited to Ringer's mixture, contains the water of 5% glucose and manages saline half a lifetime; (s) ethanol; (t) phosphate buffer; (v) used nontoxic compatible material in the other drug preparation.
Wherein said pharmaceutically acceptable carrier can be preferably from filler, disintegrating agent, binding agent, lubricant, fluidizer, wetting agent, correctives, aromatic, coloring agent, dissolubility promoter, surfactant or their combination.The amount of pharmaceutically acceptable every kind of carrier in pharmaceutical composition can change in the normal ranges of this area.
Suitable filler can be selected from microcrystalline Cellulose, optimize microcrystalline Cellulose, Powderd cellulose, pre-paying starch, lactose, mannitol, sorbitol, dextrin, Icing Sugar, starch, saccharide, sugar derivatives, Polyethylene Glycol, sodium bicarbonate, calcium carbonate, calcium sulfate, calcium hydrogen phosphate, Citric acid calcium or their combination;
Suitable disintegrants can be selected from carboxymethylstach sodium, crosslinked carboxymethylstach sodium, polyvinylpolypyrrolidone, primojel, L-hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, dried starch, hydroxypropyl starch, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate or their combination;
Suitable bonding can be selected from polyvidone, hypromellose, hydroxypropyl cellulose, Icing Sugar, syrup, rubber cement, starch slurry, methylcellulose, ethyl cellulose, sodium carboxymethyl cellulose or their combination; Polyvidone is preferably 30 POVIDONE K 30 BP/USP 30, starch slurry or hypromellose;
Examples of suitable lubricants can be selected from magnesium stearate, calcium stearate, stearic acid, calcium silicates, Talcum or their combination;
Suitable fluidizer can be selected from micropowder silica gel, Pulvis Talci, magnesium trisilicate, cellulose powder, starch or their combination;
Suitable wetting agent or solvent can be selected from water, ethanol, Polyethylene Glycol or ethanol water; Be preferably water or ethanol water; Ethanol water is preferably 30%～90% ethanol water;
Suitable correctives is selected from sucrose, Icing Sugar, sucralose, steviosin, saccharin sodium, aspartame, lactose or their combination;
Suitable aromatic is selected from water quality essence, emulsifying essence, Water/oil dual-purpose essence, panchromatic essence or their combination, and wherein water quality essence is selected from strawberry essence, apple essence, flavoring banana essence, flavoring pineapple essence, flavoring orange essence, honey peach essence, Fructus Citri Limoniae essence, fragrant citrus essence, hami melon essence, Fructus Fragariae Ananssae powdered flavor, Fructus Ananadis comosi powdered flavor or their combination;
Suitable coloring agent be selected from carmine, lemon yellow, sunset yellow, amaranth, erythrosine, newly red, red pigment of cowberry, capsanthin of red, indigo, light blue, beet red, lac, red rice is red or their combination;
Suitable dissolubility promoter or dissolution promoter can be selected from polyvinylpolypyrrolidone, polyvidone, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate or their combination;
Suitable surfactant can be selected from sodium lauryl sulphate, Polysorbate, poloxamer, span (Span), lecithin, dodecyl sodium sulfate or their combination.
Pharmaceutically acceptable salt of the present invention refers to can be according to normally used nontoxic salt in the pharmaceutical industries of method preparation well known in the art.On the one hand, based on inorganic acid salts such as the halogen acid salt of the preferred hydrofluoride of the salt of basic group, hydrochlorate, hydrobromate, hydriodate and so on, nitrate, perchlorate, sulfate, phosphate; Acylates such as the aromatic sulfonic acid salt of the lower alkane sulfonate of mesylate, fluoroform sulphonate, esilate and so on, benzene sulfonate, tosilate and so on, maleate, acetate, malate, fumarate, hemifumarate, succinate, citrate, succinate, Ascorbate, tartrate, acetate, trifluoroacetate, lactate, malonate, tosilate, oxalates; And the amino acid salts of glycinate, lysinate, arginine salt, ornithine salt, glutamate, Glu, aspartate and so on; On the other hand, based on alkali salt, the aluminum salt of the alkali metal salt of the salt particular certain cancers of acidic-group, potassium salt, lithium salts and so on, calcium salt, magnesium salt and so on, slaines such as iron salt; The inorganic salt of ammonium salt and so on, t-octanylamine salt, dibenzyl amine salt, alkylbenzyldimethylasaltsum saltsum, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-NMG salt, guanidinesalt, diethyl amine salt, triethylamine salt, hexanamine salt, N, the amine salt such as organic salt of N '-dibenzyl ethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl-1-phenylethylamine salt, piperazine salt, tetramethyl ammonium, three (methylol) aminomethane salt and so on; And the amino acid salts of glycinate, lysinate, arginine salt, ornithine salt, glutamate, Glu, aspartate and so on.Should be understood that described nontoxic salt comprises pharmaceutically acceptable pharmacological activity derivant; Or with the chemical compound of its significant correlation, include but not limited to mixture, crystallization, partially crystallizable, amorphous forms or polycrystalline form, solvate, hydrate, oxide, fragment or the radiosiotope of any ratio of salt, pharmaceutically acceptable salt, prodrug, active metabolite, various isomer or these isomers.
More preferably, the percentage by weight of wherein said Sha Gelieting or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier is: Sha Gelieting or its pharmaceutically acceptable salt 0.01%-90%, pharmaceutically acceptable carrier total amount 10%-99.99%; Be preferably Sha Gelieting or its pharmaceutically acceptable salt 0.05%-50%, pharmaceutically acceptable carrier total amount 50%-99.95%; More preferably Sha Gelieting or its pharmaceutically acceptable salt 0.1%-25%, pharmaceutically acceptable carrier total amount 75%-99.9%.
Oral formulations of the present invention can prepare with the conventional method in the pharmaceuticals industry; Can adopt wet granulation, dry granulation, fluidized bed granulation, spray-drying process, wet-mixed granulation, spherocrystal pelletize or solid dispersion to granulate; Also can adopt the direct powder compression tabletting; Packing after capsule can be granulated also can be with packing behind the direct mixing of supplementary material.
Like the described oral formulations of claim (1), it is characterized in that (2) described Sha Gelieting or its pharmaceutically acceptable salt are not the Sha Gelieting hydrochlorates; Be preferably: the trifluoroacetate of Sha Gelieting; Hydrobromate; Nitrate; Ammonium sulfate; Tartrate; Fumarate; Benzoate; Mesylate; Benzene sulfonate; Butene dioic acid salt; Tosilate; Maleate; Sulfate; Phosphate; Fumarate; Succinate; Acetate; Malate; Hemifumarate; Citrate; Succinate; Perchlorate; Hydrofluoride; Hydriodate; Ascorbate; Acetate; Lactate; Malonate; Oxalates; Fluoroform sulphonate; Esilate; Glycinate; Lysinate; Arginine salt; Ornithine salt; Glutamate, Glu or aspartate; More preferably: the trifluoroacetate of Sha Gelieting, hydrobromate, nitrate, ammonium sulfate, tartrate, fumarate or benzoate; Further be preferably: Sha Gelieting trifluoroacetate or Sha Gelieting benzoate; Most preferably be: the Sha Gelieting trifluoroacetate.
More preferably, the percentage by weight of described Sha Gelieting or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier is: Sha Gelieting or its pharmaceutically acceptable salt 0.01%-90%, pharmaceutically acceptable carrier total amount 10%-99.99%; Be preferably Sha Gelieting or its pharmaceutically acceptable salt 0.05%-50%, pharmaceutically acceptable carrier total amount 50%-99.95%; More preferably Sha Gelieting or its pharmaceutically acceptable salt 0.1%-25%, pharmaceutically acceptable carrier total amount 75%-99.9%; Wherein said Sha Gelieting or its pharmaceutically acceptable salt are not the Sha Gelieting hydrochlorates.
Like the described oral formulations of claim (1), it is characterized in that (3) described Sha Gelieting or its pharmaceutically acceptable salt are the Sha Gelieting hydrochlorate, wherein said oral formulations is dispersible tablet, drop pill, granule or dry suspension.
The Sha Gelieting hydrochlorate of 1～40mg of the present invention; Be preferably 1～20mg, more preferably 1～10mg further is preferably about 1.25mg, about 2.5mg, about 5mg or about 10mg.
Like the described oral formulations of claim (3), it is characterized in that (4) described oral formulations is a dispersible tablet.
Often because of disintegrate and the slow abundant absorption that influences medicine of medicine stripping, the patient of old man, child and dysphagia often takes and has any problem conventional tablet; Big or need once take the sheet number more for a long time when drug dose, specification, problem is particularly outstanding.Though the liquid preparation taking convenience, less stable, all inconvenience of packing, transportation, storage, and be difficult for accurately grasp taking dose.Dispersible tablet has the advantage of tablet and liquid preparation concurrently, has overcome both deficiencies; Compare with conventional tablet, dispersible tablet have disperse rapidly evenly, disintegration time is short, the medicine stripping is rapid, drug absorption is fast, bioavailability is high, untoward reaction is few and take characteristics easily.Dispersible tablet can add after the aqueous dispersion oral, also can dispersible tablet be contained in and suck clothes in the mouth or swallow.
The dispersible tablet listing is abroad promptly arranged in the eighties in last century.British Pharmacopoeia 1980 editions has promptly recorded dispersible tablet, and European Pharmacopoeia 2003 editions also records.At present; The dispersible tablet of a plurality of kinds of China national Drug Administration approved gets into clinical research and listing, for example Azithromycin dispersible tablet, roxithromycin dispersing tablet, Nateglinide dispersible tablet, amoxicillin dispersible tablet, cefaclor dispersible tablet and cefixime dispersible tablet.
Because the Sha Gelieting hydrochlorate is insoluble in water; Therefore the present invention processes dispersible tablet with the Sha Gelieting hydrochlorate; Not only meet the Chinese Pharmacopoeia requirement; And have the advantage faster than conventional tablet and capsule disintegrate, that the drug effect performance is faster, dissolution is high, the bioavailability significance improves, and brought convenience to clinical application, obtained beyond thought therapeutic effect.
Wherein said dispersible tablet can randomly carry out film coating or sweet tablet; Can be the gastric solubleness coating, also can be enteric coating.
(5) like claim (3), (4) each described dispersible tablet; It is characterized in that, can adopt wet granulation, dry granulation, fluidized bed granulation, spray-drying process, wet-mixed granulation, spherocrystal pelletize or solid dispersion granulation or direct compression process preparation; Be preferably wet granulation.
Dispersible tablet is applicable to common tablet producing technology, comprises wet granule compression tablet, dry granulation tabletting, powder/crystallization direct compression or freeze-drying.Method of granulating is preferably wet granulation, dry granulation, fluidized bed granulation, spray-drying process, wet-mixed granulation, spherocrystal pelletize or solid dispersion and granulates, and all can adopt appropriate method to process dispersible tablet.
(6) like claim (4), (5) each described dispersible tablet; It is characterized in that the percentage by weight of wherein said Sha Gelieting hydrochlorate and pharmaceutically acceptable carrier total amount is: Sha Gelieting hydrochlorate 0.1%-50%, pharmaceutically acceptable carrier total amount 50%-99.9%; Be preferably Sha Gelieting hydrochlorate 0.2%-25%, pharmaceutically acceptable carrier total amount 75%-99.8%; More preferably Sha Gelieting hydrochlorate 0.5%-25%, pharmaceutically acceptable carrier total amount 75%-99.5%.
(7) like the described drop pill of claim (3), granule or dry suspension; It is characterized in that the percentage by weight of wherein said Sha Gelieting hydrochlorate and pharmaceutically acceptable carrier total amount is: Sha Gelieting hydrochlorate 0.01%-90%, pharmaceutically acceptable carrier total amount 10%-99.99%; Be preferably Sha Gelieting hydrochlorate 0.05%-50%, pharmaceutically acceptable carrier total amount 50%-99.95%; More preferably Sha Gelieting hydrochlorate 0.1%-25%, pharmaceutically acceptable carrier total amount 75%-99.9%.
(8) a kind of method for preparing claim (3) to (6) each described dispersible tablet is characterized in that described method for preparing comprises:
(A) with Sha Gelieting hydrochlorate micronization, subsequent use;
(B) with the pulverizing of sieving respectively of various pharmaceutically acceptable carriers, filler that then will be wherein, in disintegrating agent, surfactant and/or correctives, aromatic, coloring agent mix homogeneously in mixing apparatus;
(C) with micronized Sha Gelieting, with the filler of mix homogeneously, in disintegrating agent, surfactant and/or correctives, aromatic, coloring agent mix homogeneously in mixing apparatus;
(D) take by weighing binding agent, process 2～15% adhesive solution in the water-soluble or ethanol-water solution, use as binding agent;
(E) will be the various supplementary materials of mix homogeneously add and make soft material in the above-mentioned adhesive solution, granulations of sieving, oven dry, granulate, adding fluidizer, lubricant and add disintegrating agent, mix homogeneously makes the Sha Gelieting granule, and is subsequent use;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate sheet;
(G) use tablet machine that the Sha Gelieting granule is pressed into dispersible tablet, get final product.
(9) a kind of method for preparing described granule of claim (3) or dry suspension is characterized in that described method for preparing comprises:
(A) with the pulverizing of sieving of Sha Gelieting hydrochlorate, subsequent use;
(B) with various pharmaceutically acceptable carriers sieve respectively pulverizing, mix homogeneously in mixing apparatus such as V-Mixer, trough type mixing machine or three-dimensional movement mixer then;
The Sha Gelieting hydrochlorate that (C) will sieve and various pharmaceutically acceptable carrier mix homogeneously in mixing apparatus such as V-Mixer, trough type mixing machine or three-dimensional movement mixer of mix homogeneously;
(D) get in the water-soluble or ethanol-water solution of the binding agent of recipe quantity, process 2～15% adhesive solution, use as binding agent;
(E) will be the various supplementary materials of mix homogeneously add and make soft material in the above-mentioned adhesive solution, granulations of sieving dried, granulate makes the Sha Gelieting granule, and is subsequent use;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate bag;
(G) use the granule racking machine that the Sha Gelieting granule is distributed into granule or dry suspension, get final product.
(10) be used for treating the application of the medicine of patient's diabetes or relevant disease in preparation like each described oral formulations of claim (1) to (7).
Term " patient " refers to animal, preferred mammal, and optimum is chosen, and comprises masculinity and femininity.
The specific embodiment
Specify the present invention below in conjunction with embodiment.
Embodiment 1: hydrochloric acid Sha Gelieting dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) | Dosage 4 (mg) |
| Hydrochloric acid Sha Gelieting | 1.40 | 2.79 | 5.58※ | 11.16 |
| Mannitol | 40.52 | 81.05 | 162.10 | 324.20 |
| The L-hydroxypropyl cellulose | 2.50 | 5.00 | 10.00 | 20.00 |
| 30 POVIDONE K 30 BP/USP 30 | 2.50 | 5.00 | 10.00 | 20.00 |
| Sodium lauryl sulphate | 0.10 | 0.20 | 0.40 | 0.80 |
| In add carboxymethylstach sodium | 1.32 | 2.64 | 5.28 | 10.56 |
| Add carboxymethylstach sodium | 0.66 | 1.32 | 2.64 | 5.28 |
| Micropowder silica gel | 0.50 | 1.00 | 2.00 | 4.00 |
| Magnesium stearate | 0.50 | 1.00 | 2.00 | 4.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount | In right amount |
| Sheet is heavy | 50.00 | 100.00 | 200.00 | 400.00 |
※ presses anhydride and calculates, and hydrochloric acid Sha Gelieting 5.58g is equivalent to Sha Gelieting 5.0g, down together.
Method for preparing:
(A) with hydrochloric acid Sha Gelieting micronization, particle diameter is controlled between 50～150 μ m, and is subsequent use;
(B) mannitol, L-hydroxypropyl cellulose, sodium lauryl sulphate, carboxymethylstach sodium (in add, add), micropowder silica gel and magnesium stearate are crossed 80 mesh sieves respectively and pulverize, then with mannitol, L-hydroxypropyl cellulose, in add carboxymethylstach sodium and sodium lauryl sulphate mix homogeneously in trough type mixing machine;
(C) with micronized hydrochloric acid Sha Gelieting, with the mannitol of mix homogeneously, L-hydroxypropyl cellulose, in add carboxymethylstach sodium and sodium lauryl sulphate in V-Mixer by the equivalent method mix homogeneously that progressively increases;
(D) take by weighing 30 POVIDONE K 30 BP/USP 30, be dissolved in and process 5% 30 POVIDONE K 30 BP/USP 30 alcoholic solution in 30% alcoholic solution, make adhesive and use;
(E) incite somebody to action the various supplementary materials of mix homogeneously, add and make soft material in above-mentioned 30 POVIDONE K 30 BP/USP 30 alcoholic solution, cross 30 mesh sieves and granulate; 60 ℃～80 ℃ oven dry add micropowder silica gel, add carboxymethylstach sodium and magnesium stearate, cross 18 mesh sieve granulate; Make the Sha Gelieting granule, subsequent use;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate sheet;
(G) use tablet machine that the Sha Gelieting granule is pressed into dispersible tablet, process 1000, get final product.
Embodiment 2: hydrochloric acid Sha Gelieting dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) | Dosage 4 (mg) |
| Hydrochloric acid Sha Gelieting | 1.40 | 2.79 | 5.58 | 11.16 |
| Mannitol | 40.52 | 81.05 | 162.10 | 324.20 |
| Polyvinylpolypyrrolidone | 2.50 | 5.00 | 10.00 | 20.00 |
| 30 POVIDONE K 30 BP/USP 30 | 2.50 | 5.00 | 10.00 | 20.00 |
| Sodium lauryl sulphate | 0.10 | 0.20 | 0.40 | 0.80 |
| In add carboxymethylstach sodium | 1.32 | 2.64 | 5.28 | 10.56 |
| Add carboxymethylstach sodium | 0.66 | 1.32 | 2.64 | 5.28 |
| Micropowder silica gel | 0.50 | 1.00 | 2.00 | 4.00 |
| Magnesium stearate | 0.50 | 1.00 | 2.00 | 4.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount | In right amount |
| Sheet is heavy | 50.00 | 100.00 | 200.00 | 400.00 |
Method for preparing:
(A) with hydrochloric acid Sha Gelieting micronization, particle diameter is controlled between 50～150 μ m, and is subsequent use;
(B) mannitol, polyvinylpolypyrrolidone, sodium lauryl sulphate, carboxymethylstach sodium (in add, add), micropowder silica gel and magnesium stearate are crossed 80 mesh sieves respectively and pulverize, then with mannitol, polyvinylpolypyrrolidone, in add carboxymethylstach sodium and sodium lauryl sulphate mix homogeneously in trough type mixing machine;
(C) with micronized hydrochloric acid Sha Gelieting, with the mannitol of mix homogeneously, polyvinylpolypyrrolidone, in add carboxymethylstach sodium and sodium lauryl sulphate in V-Mixer by the equivalent method mix homogeneously that progressively increases;
(D) take by weighing 30 POVIDONE K 30 BP/USP 30, be dissolved in and process 5% 30 POVIDONE K 30 BP/USP 30 alcoholic solution in 30% alcoholic solution, make adhesive and use;
(E) incite somebody to action the various supplementary materials of mix homogeneously, add and make soft material in above-mentioned 30 POVIDONE K 30 BP/USP 30 alcoholic solution, cross 40 mesh sieves and granulate; 60 ℃～80 ℃ oven dry add micropowder silica gel, add carboxymethylstach sodium and magnesium stearate, cross 24 mesh sieve granulate; Make the Sha Gelieting granule, subsequent use;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate sheet;
(G) use tablet machine that the Sha Gelieting granule is pressed into dispersible tablet, process 1000, get final product.
Embodiment 3: hydrochloric acid Sha Gelieting drop pill
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Hydrochloric acid Sha Gelieting | 0.56 | 1.12 | 2.24 |
| Polyethylene glycol 6000 | 8.44 | 16.88 | 33.76 |
| Polyoxyethylene sorbitan monoleate | 1.00 | 2.00 | 4.00 |
| Ball is heavy | 10.00 | 20.00 | 40.00 |
Method for preparing:
(A) with hydrochloric acid Sha Gelieting in 60 ℃ of dryings 6 hours, cross 100 mesh sieves and pulverize, subsequent use;
(B) PEG6000 and polyoxyethylene sorbitan monoleate mixing post-heating to 55 ℃～60 ℃ are made fusion;
The hydrochloric acid Sha Gelieting that (C) will sieve adds in the fused solution and stirs, and moves in the dropping funnel 55 ℃～60 ℃ insulations; Adjusting dropping funnel size, dimethicone with-20～-5 or liquid paraffin are the cooling phase, the system of dripping; Process 1000 balls, filter, wash, select ball, get final product.Once oral 5 balls, once-a-day.
Embodiment 4: hydrochloric acid Sha Gelieting granule
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) | Dosage 4 (mg) |
| Hydrochloric acid Sha Gelieting | 1.40 | 2.79 | 5.58 | 11.16 |
| Mannitol | 46.00 | 92.01 | 184.02 | 368.04 |
| 30 POVIDONE K 30 BP/USP 30 | 2.50 | 5.00 | 10.00 | 20.00 |
| Sucralose | 0.05 | 0.10 | 0.20 | 0.40 |
| The Fructus Fragariae Ananssae powdered flavor | 0.05 | 0.10 | 0.20 | 0.40 |
| 30% alcoholic solution | In right amount | In right amount | In right amount | In right amount |
| Bag is heavy | 50.00 | 100.00 | 200.00 | 400.00 |
Method for preparing:
(A) hydrochloric acid Sha Gelieting is crossed 80 mesh sieves and pulverize, subsequent use;
(B) mannitol and sucralose are crossed the pulverizing of 80 mesh sieves, mix homogeneously in trough type mixing machine more respectively;
The hydrochloric acid Sha Gelieting that (C) will sieve and the mannitol, sucralose of mix homogeneously in V-Mixer by the equivalent method mix homogeneously that progressively increases;
(D) 30 POVIDONE K 30 BP/USP 30 of getting recipe quantity is dissolved in the 30% an amount of alcoholic solution, processes 5% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution, as binding agent;
(E) incite somebody to action the various supplementary materials and the Fructus Fragariae Ananssae powdered flavor of mix homogeneously, add and make soft material in 5% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution, cross 24 mesh sieves and granulate, 16 order granulate are crossed in 80 ℃ of oven dry, make the Sha Gelieting granule;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate bag;
(G) use the granule racking machine that the Sha Gelieting granule is distributed into granule, process 1000 bags, promptly get.
Embodiment 5: hydrochloric acid Sha Gelieting dry suspension
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Hydrochloric acid Sha Gelieting | 2.79 | 5.58 | 11.16 |
| Sodium citrate | 8.00 | 16.00 | 32.00 |
| The fine little plain sodium of carboxymethyl | 9.00 | 18.00 | 36.00 |
| Mannitol | 27.56 | 55.12 | 110.24 |
| Sucralose | 0.10 | 0.20 | 0.40 |
| 30 POVIDONE K 30 BP/USP 30 | 2.50 | 5.00 | 10.00 |
| The Fructus Fragariae Ananssae powdered flavor | 0.05 | 0.10 | 0.20 |
| 30% alcoholic solution | In right amount | In right amount | In right amount |
| Bag is heavy | 50.00 | 100.00 | 200.00 |
Method for preparing:
(A) hydrochloric acid Sha Gelieting is crossed 80 mesh sieves and pulverize, subsequent use;
(B) sodium citrate, the fine little plain sodium of carboxymethyl, mannitol and sucralose are crossed 80 mesh sieves respectively and pulverize, then mix homogeneously in trough type mixing machine;
The hydrochloric acid Sha Gelieting that (C) will sieve and the fine little plain sodium of sodium citrate, carboxymethyl, mannitol, sucralose of mix homogeneously in V-Mixer by the equivalent method mix homogeneously that progressively increases;
(D) 30 POVIDONE K 30 BP/USP 30 of getting recipe quantity is dissolved in the 30% an amount of alcoholic solution, processes 5% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution, as binding agent;
(E) incite somebody to action the various supplementary materials and the Fructus Fragariae Ananssae powdered flavor of mix homogeneously, add and make soft material in 5% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution, cross 30 mesh sieves and granulate, 16 order granulate are crossed in 80 ℃ of oven dry, make the Sha Gelieting granule;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate bag;
(G) use the granule racking machine that the Sha Gelieting granule is distributed into dry suspension, process 1000 bags, promptly get.
Embodiment 6: trifluoroacetic acid Sha Gelieting dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) | Dosage 4 (mg) |
| Trifluoroacetic acid Sha Gelieting | 1.70 | 3.40 | 6.81※ | 13.62 |
| Mannitol | 40.22 | 80.44 | 160.87 | 321.74 |
| The L-hydroxypropyl cellulose | 2.50 | 5.00 | 10.00 | 20.00 |
| 30 POVIDONE K 30 BP/USP 30 | 2.50 | 5.00 | 10.00 | 20.00 |
| Sodium lauryl sulphate | 0.10 | 0.20 | 0.40 | 0.80 |
| In add carboxymethylstach sodium | 1.32 | 2.64 | 5.28 | 10.56 |
| Add carboxymethylstach sodium | 0.66 | 1.32 | 2.64 | 5.28 |
| Micropowder silica gel | 0.50 | 1.00 | 2.00 | 4.00 |
| Magnesium stearate | 0.50 | 1.00 | 2.00 | 4.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount | In right amount |
| Sheet is heavy | 50.00 | 100.00 | 200.00 | 400.00 |
※ presses anhydride and calculates, and trifluoroacetic acid Sha Gelieting 6.81g is equivalent to Sha Gelieting 5.0g.
Method for preparing:
(A) with trifluoroacetic acid Sha Gelieting micronization, particle diameter is controlled between 50～150 μ m, and is subsequent use;
(B) mannitol, L-hydroxypropyl cellulose, sodium lauryl sulphate, carboxymethylstach sodium (in add, add), micropowder silica gel and magnesium stearate are crossed 80 mesh sieves respectively and pulverize, then with mannitol, L-hydroxypropyl cellulose, in add carboxymethylstach sodium and sodium lauryl sulphate mix homogeneously in trough type mixing machine;
(C) with micronized trifluoroacetic acid Sha Gelieting, with the mannitol of mix homogeneously, L-hydroxypropyl cellulose, in add carboxymethylstach sodium and sodium lauryl sulphate in V-Mixer by the equivalent method mix homogeneously that progressively increases;
(D) take by weighing 30 POVIDONE K 30 BP/USP 30, be dissolved in and process 5% 30 POVIDONE K 30 BP/USP 30 alcoholic solution in 30% alcoholic solution, make adhesive and use;
(E) incite somebody to action the various supplementary materials of mix homogeneously, add and make soft material in above-mentioned 30 POVIDONE K 30 BP/USP 30 alcoholic solution, cross 30 mesh sieves and granulate; 60 ℃～80 ℃ oven dry add micropowder silica gel, add carboxymethylstach sodium and magnesium stearate, cross 18 mesh sieve granulate; Make the Sha Gelieting granule, subsequent use;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate sheet;
(G) use tablet machine that the Sha Gelieting granule is pressed into dispersible tablet, process 1000, get final product.
Embodiment 7: hydrochloric acid Sha Gelieting conventional tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) | Dosage 4 (mg) |
| Hydrochloric acid Sha Gelieting | 1.40 | 2.79 | 5.58 | 11.16 |
| Microcrystalline Cellulose | 42.10 | 84.21 | 168.42 | 336.84 |
| Polyvinylpolypyrrolidone | 1.50 | 3.00 | 6.00 | 12.00 |
| 30 POVIDONE K 30 BP/USP 30 | 2.50 | 5.00 | 10.00 | 20.00 |
| Carboxymethylstach sodium | 1.00 | 2.00 | 4.00 | 8.00 |
| Micropowder silica gel | 0.50 | 1.00 | 2.00 | 4.00 |
| Magnesium stearate | 1.00 | 2.00 | 4.00 | 8.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount | In right amount |
| Sheet is heavy | 50.00 | 100.00 | 200.00 | 400.00 |
Method for preparing:
(A) hydrochloric acid Sha Gelieting is crossed 80 mesh sieves and pulverize, subsequent use;
(B) microcrystalline Cellulose, polyvinylpolypyrrolidone, carboxymethylstach sodium, micropowder silica gel and magnesium stearate are crossed 80 mesh sieves respectively and pulverize, then with microcrystalline Cellulose and polyvinylpolypyrrolidone mix homogeneously in trough type mixing machine;
The hydrochloric acid Sha Gelieting that (C) will sieve, with the microcrystalline Cellulose of mix homogeneously and polyvinylpolypyrrolidone in V-Mixer by the equivalent method mix homogeneously that progressively increases;
(D) take by weighing 30 POVIDONE K 30 BP/USP 30, be dissolved in and process 5% 30 POVIDONE K 30 BP/USP 30 alcoholic solution in 30% alcoholic solution, make adhesive and use;
(E) incite somebody to action the various supplementary materials of mix homogeneously, add and make soft material in above-mentioned 30 POVIDONE K 30 BP/USP 30 alcoholic solution, cross 30 mesh sieves and granulate; 60 ℃～80 ℃ oven dry add micropowder silica gel, carboxymethylstach sodium and magnesium stearate, cross 18 mesh sieve granulate; Make the Sha Gelieting granule, subsequent use;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate sheet;
(G) use tablet machine that the Sha Gelieting granule is pressed into tablet, process 1000, get final product.
Embodiment 8: study on the stability
The oral formulations of getting the embodiment of the invention 1～7 preparation is that 40 ± 2 ℃, relative humidity are 75 ± 5% condition held 6 months in temperature; Carry out accelerated test; Respectively at sampling at 0,1,2,3,6 the end of month once, measure by the high spot reviews project, the result sees the following form 1:
Table 1 study on the stability result
Result of the test shows that the sample of the embodiment of the invention 1～2 preparation was about for 80 seconds disintegration, and dissolution reaches about 98%, and related substance has no significant change; The sample of embodiment 3～9 preparations, related substance also has no significant change.Explanation by the oral formulations of the present invention preparation improve drug bioavailability and stable aspect its superiority is arranged.
Embodiment 9: the dissolution rate of dispersible tablet and conventional tablet relatively
Get the dispersible tablet and the conventional tablet of the embodiment of the invention 1,2,6 and 7 preparations, investigate its dissolution rate and accumulation dissolution, result of the test sees the following form 2:
Table 2 dissolution rate is measured the result
Result of the test shows that in 10 minutes, dissolution promptly reaches 98%, explain that the dispersible tablet disintegrate of the present invention's preparation is rapid, be uniformly dispersed and the dissolution height, thereby significance ground improves bioavailability, has its superiority.
Obviously, the above embodiment of the present invention only be for clearly the present invention is described and is done for example, and be not to be qualification to embodiment of the present invention.For the those of ordinary skill in affiliated field, on the basis of above-mentioned explanation, can also make other multi-form variation or change.Here need not also can't give exhaustive to all embodiments.And these belong to conspicuous variation or the change that spirit of the present invention extended out and still are among protection scope of the present invention.
Claims (10)
1. an oral formulations of treating diabetes or relevant disease is characterized in that, it is made up of the Sha Gelieting of 1～40mg or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier.
2. oral formulations as claimed in claim 1 is characterized in that, described Sha Gelieting or its pharmaceutically acceptable salt are not the Sha Gelieting hydrochlorates.
3. oral formulations as claimed in claim 1 is characterized in that, described Sha Gelieting or its pharmaceutically acceptable salt are the Sha Gelieting hydrochlorate, and wherein said oral formulations is dispersible tablet, drop pill, granule or dry suspension.
4. oral formulations as claimed in claim 3 is characterized in that, described oral formulations is a dispersible tablet.
5. like claim 3,4 each described dispersible tablets; It is characterized in that described dispersible tablet can adopt wet granulation, dry granulation, fluidized bed granulation, spray-drying process, wet-mixed granulation, spherocrystal pelletize, solid dispersion to granulate or the direct compression process preparation.
6. like claim 4,5 each described dispersible tablets; It is characterized in that the percentage by weight of wherein said Sha Gelieting hydrochlorate and pharmaceutically acceptable carrier is: Sha Gelieting hydrochlorate 0.1%-50%, pharmaceutically acceptable carrier total amount 50%-99.9%.
7. drop pill as claimed in claim 3, granule or dry suspension; It is characterized in that the percentage by weight of wherein said Sha Gelieting hydrochlorate and pharmaceutically acceptable carrier is: Sha Gelieting hydrochlorate 0.01%-90%, pharmaceutically acceptable carrier total amount 10%-99.99%.
8. a method for preparing each described dispersible tablet of claim 3 to 6 is characterized in that, described method for preparing comprises:
(A) with Sha Gelieting hydrochlorate micronization, subsequent use;
(B) with the pulverizing of sieving respectively of various pharmaceutically acceptable carriers, filler that then will be wherein, in disintegrating agent, surfactant and/or correctives, aromatic, coloring agent mix homogeneously in mixing apparatus;
(C) with micronized Sha Gelieting hydrochlorate, with the filler of mix homogeneously, in disintegrating agent, surfactant and/or correctives, aromatic, coloring agent mix homogeneously in mixing apparatus;
(D) take by weighing binding agent, process 2～15% adhesive solution in the water-soluble or ethanol-water solution, use as binding agent;
(E) will be the various supplementary materials of mix homogeneously add and make soft material in the above-mentioned adhesive solution, granulations of sieving, oven dry, granulate, adding fluidizer, lubricant and add disintegrating agent, mix homogeneously makes the Sha Gelieting granule, and is subsequent use;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate sheet;
(G) use tablet machine that the Sha Gelieting granule is pressed into dispersible tablet, get final product.
9. method for preparing described granule of claim 3 or dry suspension is characterized in that described method for preparing comprises:
(A) with the pulverizing of sieving of Sha Gelieting hydrochlorate, subsequent use;
(B) with various pharmaceutically acceptable carriers sieve respectively pulverizing, mix homogeneously in mixing apparatus such as V-Mixer, trough type mixing machine or three-dimensional movement mixer then;
The Sha Gelieting hydrochlorate that (C) will sieve and various pharmaceutically acceptable carrier mix homogeneously in mixing apparatus such as V-Mixer, trough type mixing machine or three-dimensional movement mixer of mix homogeneously;
(D) get in the water-soluble or ethanol-water solution of the binding agent of recipe quantity, process 2～15% adhesive solution, use as binding agent;
(E) will be the various supplementary materials of mix homogeneously add and make soft material in the above-mentioned adhesive solution, granulations of sieving dried, granulate makes the Sha Gelieting granule, and is subsequent use;
(F) drug content in the mensuration Sha Gelieting granule, it is heavy to calculate bag;
(G) use the granule racking machine that the Sha Gelieting granule is distributed into granule or dry suspension, get final product.
10. be used for treating the application of the medicine of diabetes or relevant disease in preparation like each described oral formulations of claim 1 to 7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102671750A CN102379869A (en) | 2010-08-31 | 2010-08-31 | Oral preparation containing saxagliptin and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102671750A CN102379869A (en) | 2010-08-31 | 2010-08-31 | Oral preparation containing saxagliptin and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102379869A true CN102379869A (en) | 2012-03-21 |
Family
ID=45819977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102671750A Pending CN102379869A (en) | 2010-08-31 | 2010-08-31 | Oral preparation containing saxagliptin and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102379869A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102086172A (en) * | 2011-01-13 | 2011-06-08 | 廖国超 | Medicinal salts of saxagliptin and preparation methods of medicinal salts |
| WO2013171766A2 (en) * | 2012-05-15 | 2013-11-21 | Hetero Research Foundation | Saxagliptin solid dispersion |
| CN103893142A (en) * | 2014-03-18 | 2014-07-02 | 薛娟 | Onglyza dispersible tablet and preparation method thereof |
| WO2014102832A3 (en) * | 2012-12-31 | 2015-03-19 | Hetero Research Foundation | Saxagliptin hydrochloride solid dispersion |
| CN104644582A (en) * | 2014-12-14 | 2015-05-27 | 天津市康瑞药业有限公司 | Vildagliptin dropping pill and preparation method thereof |
| CN105168177A (en) * | 2015-09-24 | 2015-12-23 | 江苏威凯尔医药科技有限公司 | Saxagliptin capsule and preparation method thereof |
| CN105193772A (en) * | 2015-10-28 | 2015-12-30 | 陈跃坚 | Saxagliptin oral membrane and preparation method thereof |
| CN105520913A (en) * | 2014-09-28 | 2016-04-27 | 石药集团中奇制药技术（石家庄）有限公司 | Pellet containing saxalipitin and application and preparation method of pellet containing saxalipitin |
| CN105878219A (en) * | 2016-05-19 | 2016-08-24 | 广州迈达康医药科技有限公司 | Trajenta oral membrane agent and preparation method thereof |
| CN106913535A (en) * | 2015-12-25 | 2017-07-04 | 江苏万邦生化医药股份有限公司 | A kind of DDP-4 inhibitor medicaments oral disintegrating tablet and preparation method thereof |
| WO2023107082A1 (en) * | 2021-12-09 | 2023-06-15 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A film coated tablet of saxagliptin and at least one antioxidant processed with wet granulation |
-
2010
- 2010-08-31 CN CN2010102671750A patent/CN102379869A/en active Pending
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102086172A (en) * | 2011-01-13 | 2011-06-08 | 廖国超 | Medicinal salts of saxagliptin and preparation methods of medicinal salts |
| WO2013171766A2 (en) * | 2012-05-15 | 2013-11-21 | Hetero Research Foundation | Saxagliptin solid dispersion |
| WO2013171766A3 (en) * | 2012-05-15 | 2014-01-03 | Hetero Research Foundation | Saxagliptin solid dispersion |
| WO2014102832A3 (en) * | 2012-12-31 | 2015-03-19 | Hetero Research Foundation | Saxagliptin hydrochloride solid dispersion |
| CN103893142A (en) * | 2014-03-18 | 2014-07-02 | 薛娟 | Onglyza dispersible tablet and preparation method thereof |
| CN105520913A (en) * | 2014-09-28 | 2016-04-27 | 石药集团中奇制药技术（石家庄）有限公司 | Pellet containing saxalipitin and application and preparation method of pellet containing saxalipitin |
| CN105520913B (en) * | 2014-09-28 | 2020-06-23 | 石药集团中奇制药技术（石家庄）有限公司 | Pellet containing saxagliptin, application and preparation method thereof |
| CN104644582A (en) * | 2014-12-14 | 2015-05-27 | 天津市康瑞药业有限公司 | Vildagliptin dropping pill and preparation method thereof |
| CN105168177A (en) * | 2015-09-24 | 2015-12-23 | 江苏威凯尔医药科技有限公司 | Saxagliptin capsule and preparation method thereof |
| CN105193772A (en) * | 2015-10-28 | 2015-12-30 | 陈跃坚 | Saxagliptin oral membrane and preparation method thereof |
| CN106913535A (en) * | 2015-12-25 | 2017-07-04 | 江苏万邦生化医药股份有限公司 | A kind of DDP-4 inhibitor medicaments oral disintegrating tablet and preparation method thereof |
| CN105878219A (en) * | 2016-05-19 | 2016-08-24 | 广州迈达康医药科技有限公司 | Trajenta oral membrane agent and preparation method thereof |
| CN105878219B (en) * | 2016-05-19 | 2019-10-18 | 广州迈达康医药科技有限公司 | A kind of Li Gelieting pelliculae pro cavo oris and preparation method thereof |
| WO2023107082A1 (en) * | 2021-12-09 | 2023-06-15 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A film coated tablet of saxagliptin and at least one antioxidant processed with wet granulation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102379869A (en) | Oral preparation containing saxagliptin and application thereof | |
| AU2016213722B2 (en) | Solid dispersion of rifaximin | |
| JP6396980B2 (en) | Bendamustine solid dosage form | |
| EP3167876B1 (en) | Pharmaceutical tablet formulation for the veterinary medical sector, method of production and use thereof | |
| CN102078309A (en) | Dispersible tablet containing antipsychotic medicines and application thereof | |
| CN101516344A (en) | Pharmaceutical compositions comprising nilotinib or its salt | |
| CN104650091B (en) | The micronization of ticagrelor and crystal formation thereof, and preparation method and medicinal application | |
| CN1482903A (en) | Nateglinide-containing preparation | |
| JP2016166230A (en) | Nalbuphine-containing formulations and uses thereof | |
| US20110008428A1 (en) | Solid pharmaceutical composition comprising a non-peptide angiotensin ii receptor antagonist and a diuretic | |
| US20200376004A1 (en) | Amorphous onapristone compositions and methods of making the same | |
| CN102813664A (en) | Oral enteric preparation containing Grel drugs and aspirin | |
| WO2015114314A1 (en) | Pharmaceutical composition comprising abiraterone | |
| JP2011500811A (en) | Clavulanic acid pharmaceutical formulation | |
| JP6639368B2 (en) | Solid preparation for treating diabetes | |
| JP2020510625A (en) | Pharmaceutical composition containing celecoxib | |
| CN102125540A (en) | Pharmaceutically acceptable composition containing ambroxol in non-salt form | |
| JP2022524424A (en) | Compound forms and formulations thereof with improved bioavailability | |
| CN101940559A (en) | Orally-taken solid preparation containing gastric mucosa protective agent and application thereof | |
| CN101961319B (en) | Silybin meglumine enteric agent with high bioavailability and preparation method thereof | |
| CN102805749A (en) | Dispersible tablet comprising clopidogrel and aspirin | |
| RU2690685C2 (en) | Pharmaceutical compositions containing alpelisib | |
| CN102793718A (en) | Pharmaceutical composition including aspirin salt and aluminium magnesium salt | |
| EP3305282A2 (en) | Composition of pranlukast-containing solid preparation with improved bioavailability and method for preparing same | |
| CN115124419B (en) | Rhein and cytisine eutectic crystal, preparation method, composition and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120321 |