WO2016105084A2 - 당뇨병 치료용 약제학적 조성물 - Google Patents
당뇨병 치료용 약제학적 조성물 Download PDFInfo
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- WO2016105084A2 WO2016105084A2 PCT/KR2015/014096 KR2015014096W WO2016105084A2 WO 2016105084 A2 WO2016105084 A2 WO 2016105084A2 KR 2015014096 W KR2015014096 W KR 2015014096W WO 2016105084 A2 WO2016105084 A2 WO 2016105084A2
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- pharmaceutical composition
- dpp
- treating diabetes
- inhibitor
- cellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
Definitions
- the present invention relates to a pharmaceutical composition for treating diabetes, more specifically metformin and metepin (dipeptidyl peptidase 4, DPP-IV, hereinafter referred to as DPP-IV, an enzyme that plays an important role in the mechanism of diabetes). It relates to a pharmaceutical composition for treating diabetes comprising an inhibitor.
- DPP-IV inhibitors and metformin are pharmaceutical compounds for the treatment of diabetes well known in the art.
- Korean Patent Publication Nos. 2014-0021049 and 2008-0056171 disclose a pharmaceutical composition comprising a DPP-IV inhibitor and metformin and a method of preparing the same.
- the inventors of the present invention while developing a combination of a DPP-IV inhibitor and metformin, found that when the DPP-IV inhibitor and metformin are contacted on a single agent, they affect the stability of the DPP-IV inhibitor. . In addition, it was found that the amount, or ratio, of the isolation layer that inhibits contact of metformin with the DPP-IV inhibitor affects the stability of the DPP-IV inhibitor.
- the drug in the development of a combination, the drug must be released to the extent that the drug can be absorbed into the body, but the formulation of the combination is not easy because the physical and chemical properties of each substance are different. Even if a formulation having a desirable elution is developed, it may be difficult to apply due to problems such as cost or residual solvent.
- the inventors of the present invention completed the present invention while developing a formulation that can improve the stability of the DPP-IV inhibitor and exhibit a desired dissolution pattern in a pharmaceutical composition for treating diabetes containing both the DPP-IV inhibitor and metformin. .
- Patent Document 1 Republic of Korea Patent Publication No. 2008-0056171
- Patent Document 2 Republic of Korea Patent Publication No. 2014-0021049
- Non-Patent Document 1 Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2013: 6 187-95
- Another object of the present invention is to provide a pharmaceutical composition for treating diabetes that can achieve a desired dissolution pattern.
- compositions for treating diabetes comprising a metformin and a DPP-IV inhibitor, and comprising an isolation layer for blocking contact between the metformin and the DPP-IV inhibitor.
- the pharmaceutical composition for treating diabetes according to the present invention can block the contact between the DPP-IV inhibitor and metformin, the shelf life of the composition is increased and the amount of the flexible substance is reduced as well as the amount of the flexible substance.
- the rapid release of the DPP-IV inhibitor is possible, but also has the advantage of controlling the sustained release of metformin.
- Example 1 is a diagram showing the results of the DPP-IV inhibitor (tenerigliptin) dissolution test of the positive control group, Example 2 and Comparative Example 1.
- the present invention is metformin; It relates to a pharmaceutical composition for treating diabetes comprising a DPP-IV inhibitor, and comprising an isolation layer for blocking contact between the metformin and the DPP-IV inhibitor.
- Metformin is an agent for treating biguanide type 2 diabetes and increases sensitivity to insulin in human peripheral tissues. It is also involved in inhibiting the absorption of glucose in the intestine, inhibiting hepatic gluconeogenesis, and inhibiting fatty acid oxidation. Typical doses administered to diabetics are 250 mg to 1000 mg.
- DPP-IV dipeptidyl peptidase-IV
- the mechanism of the DPP-IV inhibitor is as follows.
- GLP-1 glucagon-like peptide-1
- GIP gastric inhibitory peptides
- methformin includes all of metformin or its pharmaceutically acceptable salts, crystalline forms, hydrates, solvates, diastereomers or enantiomers thereof.
- DPP-IV inhibitor includes all of the DPP-IV inhibitors or pharmaceutically acceptable salts thereof, crystalline forms, hydrates, solvates, diastereomers or enantiomers thereof.
- DPP-IV inhibitor also refers to all active metabolites and prodrugs thereof, including all active metabolites and prodrugs of DPP-IV inhibitors.
- the "metabolite” is an active derivative of a DPP-IV inhibitor produced when the DPP-IV inhibitor is metabolized, and the "prodrug” is metabolized to a DPP-IV inhibitor or the same metabolite as the DPP-IV inhibitor ( Are metabolized to
- DPP-IV inhibitors are known in the art.
- Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Anagliptin, Teneligliptin, Allogliptin (Alogliptin), Gemigliptin, Duogliptin, and the like and the most preferred DPP-IV inhibitor of the present invention is tenerliptin.
- Tenerigliptin has the advantage of achieving a desirable blood glucose reduction effect only once a day administration.
- the "pharmaceutically acceptable salts” refer to salts prepared using non-toxic or less organic or inorganic acids, or bases.
- the organic acid is, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid , Glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxy acetic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid salts.
- the above-mentioned acid addition salts may be a) directly mixing the compound of formula 1 and an acid, b) dissolving and mixing one of them in a solvent or a hydrous solvent, or c) solvent or submerging the compound of formula 1 It is prepared by a general salt preparation method which is placed in an acid in a solvent and mixed with them.
- salts that can be additionally salted are Gabar salt, Gabapentin salt, Pregabalin salt, Nicotinate, Adipate salt, Hemimalonate, Cysteine salt, Acetylcysteine salt, Methionine salt, Arginine salt, Lysine salt, Ornithine salt, Aspartate.
- Pharmaceutically acceptable base addition salts include, but are not limited to, salts consisting of sodium, potassium, calcium, ammonium, magnesium or organic amino.
- the inventors of the present invention have found that when the DPP-IV inhibitor and metformin are in physical contact with each other, the stability of the DPP-IV inhibitor is significantly reduced compared to otherwise.
- a pharmaceutical composition comprising both a DPP-IV inhibitor and metformin and then measured the stability of the two active ingredients, when the two active ingredients are not physically isolated by the isolation layer Remarkably lower levels of analogues were measured. In addition, the shelf life was expected to increase by more than 300% compared to the control (see Experimental Example 1).
- an isolation layer must exist to physically block the contact between the two to secure the stability.
- isolation layer is meant a means that can block the contact of the DPP-IV inhibitor with metformin, the embodiments encompassing all means that can be used in oral formulations in the art, such as membranes, walls, coatings.
- the oral dosage form is metformin in the inner layer
- the DPP-IV inhibitor is included in the outer layer and between the inner layer and the outer layer to form an intermediate layer between the two Formulations that block contact.
- metformin is slowly and incompletely absorbed by the gastrointestinal tract and is mainly absorbed in the upper intestine.
- the half-life of blood is known to be 2-6 hours, the solubility of the drug itself is very high, the absorption is very low, and the drug half-life is short. Therefore, it is necessary to formulate into a sustained release to release the drug slowly, for this purpose it is advantageous to dissolve the drug disposed on the inside rather than the outside of the oral formulation.
- the two active ingredients were isolated by the isolation layer.
- the dissolution rate was much higher than that of the case (see Experimental Example 2).
- an isolation layer must be present to prevent contact between them in order to obtain a desirable elution pattern.
- the inner layer containing metformin may further include a swellable polymer for sustained release.
- the swellable polymer is a high viscosity hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose sodium, cross-linked carboxymethyl cellulose and its derivatives, methyl cellulose, ethyl cellulose and salts or derivatives thereof, carboxy vinyl polymer, polyvinyl At least one selected from the group consisting of alcohols, polyethylene oxide (PEO), polymethacrylate polymers, and pharmaceutically acceptable biodegradable cellulose derivatives.
- the swellable polymer is effective to achieve the desired elution pattern of metformin contained in the inner layer.
- the swellable polymer has a viscosity of 1,000 to 200,000 centipoas (cps), preferably 4,000 to 200,000 centipoas (cps) is preferable for implementing excellent dissolution properties.
- the viscosity of all the polymers was measured using a viscometer commonly used in the art in an aqueous solution of 2% by weight.
- the viscosity of the swellable polymer is lower than 1000 centipoise or higher than 200,000 centipoise, it may be difficult to achieve a desired dissolution pattern when the pharmacokinetic behavior of metformin is followed.
- the high viscosity cellulose derivative is 20 to 50% by weight relative to the total weight of the pharmaceutical composition of the present invention to achieve a preferable dissolution pattern.
- the weight of the composition means dry weight.
- the swellable polymer is lower than 20% by weight or higher than 50% by weight relative to the total weight of the pharmaceutical composition of the present invention, it may be difficult to achieve the desired dissolution pattern when depending on the pharmacokinetic behavior of metformin.
- the inner layer may further comprise a pharmaceutically acceptable excipient well known in the art.
- a pharmaceutically acceptable excipient well known in the art.
- fillers, disintegrants, lubricants, binders and the like commonly used in the field to which the present invention pertains may further include within the scope of not impairing the object of the present invention.
- the pharmaceutical composition of the present invention is to be placed on the outside when the pharmaceutical composition of the present invention is to be prepared for oral use because the DPP-IV inhibitor drug must be shown to be fast-acting.
- the outer layer containing the DPP-IV inhibitor is hydroxypropylmethylcellulose (HPMC), carboxymethylcellulose (CMC), microcrystalline cellulose (MCC), polyvinyl alcohol, methylcellulose (MC), hydroxypropylcellulose (HPC) And at least one release controlling agent selected from the group consisting of cellulose acetate phthalate (CAP), hydroxypropyl methyl cellulose phthalate (HPMCP), hydroxypropyl methyl cellulose acetate succinate (HPMCAS), and polymethacrylate polymers. can do.
- the outer layer may also further comprise pharmaceutically acceptable excipients well known in the art.
- pharmaceutically acceptable excipients well known in the art.
- fillers, disintegrants, lubricants, binders and the like commonly used in the field to which the present invention pertains may further include within the scope of not impairing the object of the present invention.
- At least one water-soluble polymer selected from the group consisting of hydroxypropylmethylcellulose (HPMC), carboxymethylcellulose (CMC), polyvinyl alcohol and hydroxypropylcellulose (HPC), which blocks the contact of the DPP-IV inhibitor with metformin. It may further include.
- Such an intermediate layer may further include plasticizers, lubricants, coating aids, fillers, and the like, which are commonly used in the field of the present invention within the scope of not impairing the object of the present invention.
- the intermediate layer is preferably about 2 to 5% by weight based on the total weight of the pharmaceutical composition for treating diabetes of the present invention.
- the weight of the composition means dry weight.
- the segregation of the DPP-IV inhibitor and the metformin is not performed properly, resulting in stability of the DPP-IV inhibitor There was a problem that the deterioration, the stability of the DPP-IV inhibitor even when higher than 5% by weight.
- the pharmaceutical composition for treating diabetes of the present invention may be administered orally or parenterally, but it is more preferably prepared for oral use.
- Oral formulations have the advantages of easy administration, improved patient compliance, and reduced manufacturing and maintenance costs.
- compositions that can be administered orally include tablets, granules, pellets, pills, powders, suspensions, capsules, including uncoated tablets, film-coated tablets, dragees, enteric tablets, multi-layered tablets, chewed tablets, sublingual tablets, thin tablets, and the like. All oral forms that one of ordinary skill in the art would recognize, such as, troches, powders, and the like.
- the invention also comprises the steps of i) preparing an inner layer comprising metformin; ii) coating the inner layer surface with at least one water-soluble polymer selected from the group consisting of hydroxypropylmethylcellulose (HPMC), carboxymethylcellulose (CMC), and hydroxypropylcellulose (HPC) to prepare an intermediate layer; iii) preparing a pharmaceutical composition for treating diabetes, comprising preparing an outer layer comprising a DPP-IV inhibitor on the surface of the intermediate layer, and a more preferable method of such manufacturing method is related to the pharmaceutical composition. It is to be made the same as described.
- Examples 1 to 3 were prepared according to the compositions and doses listed in Table 1.
- metformin hydrochloride, hydroxypropylmethylcellulose 100,000 centipoise (cps) (measured in a 2% by weight aqueous solution), carboxymethylcellulose sodium and polyvinylpyrrolidone K-30 are mixed homogeneously in a mixer, and a certain amount of water is mixed It was added to obtain wet granules, and then the granules obtained by passing them through a 14 mesh sieve were dried in a fluid bed dryer. Magnesium stearate was added to the dried granules and mixed to obtain granules having excellent flowability and compressibility. Then, the metformin inner layer (coated tablet) was obtained according to a conventional tableting method.
- a coating solution was prepared to prepare an intermediate layer for blocking contact of metformin with a DPP-IV inhibitor.
- Example 1 Example 2
- Example 3 Hydroxypropylmethylcellulose 4.5cps 35.7 47.6 59.6
- Polyethylene glycol 6.8 9.1 11.3
- polyethylene glycol and purified water were mixed, and hydroxypropylmethylcellulose (4.5 cps) was added to the prepared polyethylene glycol aqueous solution, followed by mixing until a homogeneous drug coating solution.
- the coating solution prepared above was sprayed onto the inner layer containing metformin prepared in 1-a to form an intermediate layer.
- tenerigliptin, polyethylene glycol and hydroxypropylmethylcellulose (4.5 cps) were homogeneously dispersed in purified water and mixed until a homogeneous drug coating solution was obtained.
- the pharmaceutical solution of the present invention was prepared by spraying the coating solution prepared above on a tablet having an inner layer and an intermediate layer, followed by drying in a coating machine.
- Tablets were prepared in the same composition and method as in Examples 1 to 3, except that no intermediate layer was formed (the intermediate layer was absent).
- the formulations were prepared in the same compositions and methods as in Examples 1 to 3, except that the amount of interlayer coating was adjusted as described in Table 4 below.
- the stability comparison test was conducted under the conditions of the harsh test among the stability test methods specified by the International Harmonic Organization (ICH). Three days at 60 °C temperature, 75% relative humidity was measured, the results are shown in Table 5 below.
- ICH International Harmonic Organization
- compositions comprising both a DPP-IV inhibitor and metformin, it was determined how the presence of the sequestering layer affected the release properties of DPP-IV.
- Example 2 and Comparative Example 1 were tested according to the elution method described in USP (Method II) at 50 rpm in 900 ml eluate of pH 9.0 Tris buffer at 37 ° C., respectively, and the eluate was taken at each time period and the high pressure liquid chromatograph described in USP. According to the content of tenerigliptin was measured. Tenellinia tablets were used as a positive control.
- Example 2 (%) Comparative Example 1 (%) 10 71.6 81.1 68.7 15 92.2 88.7 78.2 30 103.3 94.2 86.8 45 103.8 95.6 88.9
- Example 2 having an intermediate layer separating two active ingredients of tenerliptin and metformin showed a dissolution pattern almost similar to that of the positive control group, whereas Comparative Example 1 having no intermediate layer was present. The pattern was different from that of the positive control group.
- the similarity factor (f2) was calculated according to the Drug Equivalence Test Standard for the Ministry of Food and Drug Safety (equivalence is recognized if the similarity factor is greater than 50). Same as 7.
- Example 2 was found to be equivalent to the positive control group, while Comparative Example 1 was found not to be recognized.
Abstract
Description
조성 | 용량 (mg) |
메트포르민 염산염 | 1000 |
하이드록시프로필메칠셀룰로오스 (100,000 cps) | 313 |
카르복시메칠셀룰로오스 소디움 | 50 |
폴리비닐피롤리돈 K-30 | 40 |
마그네슘 스테아레이트 | 15 |
조성 | 용량 (mg) | ||
실시예 1 | 실시예 2 | 실시예 3 | |
하이드록시프로필메칠셀룰로오즈 4.5cps | 35.7 | 47.6 | 59.6 |
폴리에칠렌글리콜 | 6.8 | 9.1 | 11.3 |
정제수 | 297.8 | 397.0 | 496.3 |
조성 | 용량 (mg) |
하이드록시프로필메칠셀룰로오즈 (4.5 cps) | 50 |
폴리에틸렌글리콜 | 10 |
테네리글립틴 | 31 |
정제수 | 630 |
조성 | 용량 (mg) | |
비교예 2 | 비교예 3 | |
하이드록시프로필메칠셀룰로오즈 4.5cps | 23.8 | 71.5 |
폴리에칠렌글리콜 | 4.8 | 13.6 |
정제수 | 198.5 | 595.6 |
대상 | 중간층 코팅량(중량%) | days | unknown | impurity-6 | impurity C | 예측 유효기간(월) |
비교예 1 | 0 | 0 | 0 | 0 | 0.052 | 6 |
3 | 1.222 | 0.588 | 0.368 | |||
비교예 2 | 1.8 | 0 | 0 | 0 | 0.052 | 18 |
3 | 0.522 | 0.195 | 0.29 | |||
실시예 1 | 2.7 | 0 | 0 | 0 | 0.052 | 24 |
3 | 0.458 | 0.183 | 0.252 | |||
실시예 2 | 3.6 | 0 | 0 | 0 | 0.052 | 28 |
3 | 0.385 | 0.155 | 0.226 | |||
실시예 3 | 4.4 | 0 | 0 | 0 | 0.052 | 24 |
3 | 0.358 | 0.201 | 0.253 | |||
비교예 3 | 5.3 | 0 | 0 | 0 | 0.052 | 18 |
3 | 0.388 | 0.2 | 0.291 |
용출시간(분) | 테네리글립틴의 용출률 | ||
양성대조군(%) | 실시예 2(%) | 비교예 1(%) | |
10 | 71.6 | 81.1 | 68.7 |
15 | 92.2 | 88.7 | 78.2 |
30 | 103.3 | 94.2 | 86.8 |
45 | 103.8 | 95.6 | 88.9 |
실시예 2 | 비교예 1 | |
유사성인자(f2) | 54.9 | 43.9 |
결과 | 동등 | 비동등 |
Claims (15)
- 메트포르민 및;DPP-IV 억제제를 포함하고,상기 메트포르민과 DPP-IV 억제제 사이의 접촉을 차단하기 위한 격리층을 포함하는 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제1항에 있어서,상기 DPP-IV 억제제가 시타글립틴(Sitagliptin), 빌다글립틴(Vildagliptin), 삭사글립틴(Saxagliptin), 리나글립틴(Linagliptin), 아나글립틴(Anagliptin), 테네리글립틴(teneligliptin), 알로글립틴(Alogliptin), 제미글립틴(Gemigliptin) 및 듀토글립틴(Dutogliptin)으로 이루어진 군으로부터 선택된 1종 이상인 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제1항에 있어서,상기 메트포르민이 내층에 포함되고,상기 DPP-IV 억제제가 외층에 포함되며,상기 격리층이 상기 내층과 외층 사이에 배치된 중간층을 형성하는 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제3항에 있어서,상기 내층이 팽윤성 고분자를 더 포함하는 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제4항에 있어서,상기 팽윤성 고분자가 고점도의 하이드록시프로필메칠셀룰로오스, 하이드록시에칠셀룰로오스, 카르복시메칠셀룰로오스 소디움, 교차결합된 카르복시메칠셀룰로오스 및 그 유도체, 메칠셀룰로오스, 에칠셀룰로오스 및 그 염 또는 유도체, 카르복시 비닐고분자, 폴리비닐알코올, 폴리에틸렌 옥사이드 (PEO), 폴리메타크릴레이트 중합체, 및 약제학적으로 허용가능한 생분해성 셀룰로오스 유도체들로 이루어진 군으로부터 선택된 1종 이상인 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제4항에 있어서,상기 팽윤성 고분자가 1,000 내지 200,000 센티포아스(cps)의 점도를 갖는 중합체인 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제6항에 있어서,상기 팽윤성 고분자가 4,000 내지 200,000 센티포아스(cps)의 점도를 갖는 중합체인 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제4항에 있어서,상기 팽윤성 고분자가 상기 약제학적 조성물 총 중량에 대하여 20 내지 50 중량%인 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제3항에 있어서,상기 외층이 하이드록시프로필메칠셀룰로오스(HPMC), 카르복시메칠셀룰로오스(CMC), 미세결정셀룰로오스(MCC), 폴리비닐알코올, 메칠셀룰로오스(MC), 하이드록시프로필셀룰로오스(HPC), 셀룰로오스아세테이트프탈레이트(CAP), 하이드록시프로필메칠셀룰로오스프탈레이트(HPMCP), 하이드록프로필시메칠셀룰로오스아세테이트숙씨네이트(HPMCAS), 및 폴리메타아크릴레이트 중합체로 이루어진 군으로부터 선택된 1종 이상의 방출조절제를 더 포함하는 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제3항에 있어서,상기 중간층이 하이드록시프로필메칠셀룰로오스(HPMC), 카르복시메칠셀룰로오스(CMC), 폴리비닐알코올 및 하이드록시프로필셀룰로오스(HPC)로 이루어진 군으로부터 선택된 1종 이상의 수용성 중합체인 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제3항에 있어서,상기 중간층이 상기 약제학적 조성물 총 중량에 대하여 2 내지 5 중량%인 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제1항에 있어서,상기 당뇨병 치료용 약제학적 조성물이 경구용인 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제1항에 있어서,상기 메트포르민이 250 mg 내지 1000 mg 포함된 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- 제1항에 있어서,상기 DPP-IV 억제제가 25 mg 내지 100mg 포함된 것을 특징으로 하는, 당뇨병 치료용 약제학적 조성물.
- i) 메트포르민을 포함하는 내층을 제조하는 단계,ii) 상기 내층 표면을 하이드록시프로필메칠셀룰로오스(HPMC), 카르복시메칠셀룰로오스(CMC), 및 하이드록시프로필셀룰로오스(HPC)로 이루어진 군으로부터 선택된 1종 이상의 수용성 중합체로 코팅하여 중간층을 제조하는 단계,iii) 상기 중간층 표면에 DPP-IV 억제제를 포함하는 외층을 제조하는 단계를 포함하는, 당뇨병 치료용 약제학적 조성물의 제조방법.
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MYPI2017702340A MY196438A (en) | 2014-12-23 | 2015-12-22 | Pharmaceutical Composition for Treating Diabetes |
SG11201705194XA SG11201705194XA (en) | 2014-12-23 | 2015-12-22 | Pharmaceutical composition for treating diabetes |
CN201580070627.7A CN107205969B (zh) | 2014-12-23 | 2015-12-22 | 糖尿病治疗用药物组合物 |
PH12017501184A PH12017501184A1 (en) | 2014-12-23 | 2017-06-22 | Pharmaceutical composition for treating diabetes |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106421794A (zh) * | 2016-09-27 | 2017-02-22 | 黑龙江珍宝岛药业股份有限公司 | 一种用于治疗ⅱ型糖尿病的药物组合物及其制备方法 |
WO2019132833A1 (en) * | 2017-12-26 | 2019-07-04 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | The modified release combination comprising linagliptin and metformin |
CN115715768A (zh) * | 2022-11-24 | 2023-02-28 | 浙江昂利泰制药有限公司 | 一种小型西格列汀-二甲双胍缓释片及其制备方法 |
WO2023059118A1 (ko) * | 2021-10-08 | 2023-04-13 | (주)셀트리온 | 안정성이 개선된 당뇨병 치료용 약학 조성물 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2020002312A (es) * | 2017-09-29 | 2020-09-17 | Hanmi Pharm Ind Co Ltd | Farmaceutica combinada que comprende dapagliflozina l-prolina y metformina. |
KR102500835B1 (ko) * | 2017-10-24 | 2023-02-17 | 한미약품 주식회사 | 리나글립틴 및 메트포르민을 포함하는 복합제제 및 그의 제조방법 |
CN113116846B (zh) * | 2019-12-31 | 2024-03-19 | 广州玻思韬控释药业有限公司 | 胃滞留片 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006080630A1 (en) * | 2004-09-23 | 2006-08-03 | Handok Pharmaceuticals Co., Ltd. | Pharmaceutical combination preparation for oral delivery for the treatment of diabetes mellitus |
KR100760430B1 (ko) * | 2004-12-31 | 2007-10-04 | 한미약품 주식회사 | 당뇨병 치료제의 경구 투여용 서방성 복합 제제 및 이의제조 방법 |
ES2390231T3 (es) * | 2005-06-03 | 2012-11-07 | Mitsubishi Tanabe Pharma Corporation | Agentes farmacéuticos concomitantes y su uso |
CA2633167A1 (en) * | 2005-12-16 | 2007-07-12 | Merck & Co., Inc. | Pharmaceutical compositions of combinations of dipeptidyl peptidase-4 inhibitors with metformin |
CN101168060B (zh) * | 2007-10-12 | 2012-06-13 | 重庆医药工业研究院有限责任公司 | 一种含双胍和磺酰脲的稳定的药物组合物及其制备方法 |
CN101168059A (zh) * | 2007-10-12 | 2008-04-30 | 重庆医药工业研究院有限责任公司 | 一种含有双胍、磺酰脲和噻唑烷二酮的稳定的药物组合物及其制备方法 |
EP2249643A4 (en) * | 2008-02-05 | 2013-10-09 | Merck Sharp & Dohme | PHARMACEUTICAL COMPOSITIONS OF A METFORMIN AND DIPEPTIDYL PEPTIDASE-IV INHIBITOR ASSOCIATION |
CN106177958A (zh) * | 2009-02-13 | 2016-12-07 | 勃林格殷格翰国际有限公司 | 包含dpp‑4抑制剂(利拉列汀)任选地组合其它抗糖尿病药的抗糖尿病药物 |
KR101942590B1 (ko) * | 2010-07-09 | 2019-01-25 | 비에이치브이 파르마, 인크. | 레모글리플로진을 포함하는 짧은 반감기 약제용의 즉시/지연 조합 방출 전달 시스템 |
AR085689A1 (es) * | 2011-03-07 | 2013-10-23 | Boehringer Ingelheim Int | Composiciones farmaceuticas de metformina, linagliptina y un inhibidor de sglt-2 |
US9555001B2 (en) * | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
KR101409330B1 (ko) * | 2012-05-11 | 2014-06-18 | 안국약품 주식회사 | 복용순응도가 향상된 서방성 당뇨병 치료용 복합제제 및 이의 제조방법 |
KR20140013436A (ko) * | 2012-07-24 | 2014-02-05 | 한미약품 주식회사 | 메트포르민 및 로수바스타틴을 포함하는 경구용 복합 제제 |
CN103285398B (zh) * | 2013-06-28 | 2015-07-22 | 青岛黄海制药有限责任公司 | 含有dpp-ⅳ抑制剂和第二种糖尿病药物的复方制剂及其制备方法 |
-
2014
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2015
- 2015-12-22 SG SG11201705194XA patent/SG11201705194XA/en unknown
- 2015-12-22 WO PCT/KR2015/014096 patent/WO2016105084A2/ko active Application Filing
- 2015-12-22 CN CN201580070627.7A patent/CN107205969B/zh active Active
- 2015-12-22 MY MYPI2017702340A patent/MY196438A/en unknown
- 2015-12-22 TW TW104143123A patent/TW201628602A/zh unknown
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106421794A (zh) * | 2016-09-27 | 2017-02-22 | 黑龙江珍宝岛药业股份有限公司 | 一种用于治疗ⅱ型糖尿病的药物组合物及其制备方法 |
WO2019132833A1 (en) * | 2017-12-26 | 2019-07-04 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | The modified release combination comprising linagliptin and metformin |
WO2023059118A1 (ko) * | 2021-10-08 | 2023-04-13 | (주)셀트리온 | 안정성이 개선된 당뇨병 치료용 약학 조성물 |
CN115715768A (zh) * | 2022-11-24 | 2023-02-28 | 浙江昂利泰制药有限公司 | 一种小型西格列汀-二甲双胍缓释片及其制备方法 |
Also Published As
Publication number | Publication date |
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KR101526825B1 (ko) | 2015-06-08 |
MY196438A (en) | 2023-04-11 |
CN107205969A (zh) | 2017-09-26 |
TW201628602A (zh) | 2016-08-16 |
CN107205969B (zh) | 2020-06-30 |
PH12017501184B1 (en) | 2017-12-18 |
WO2016105084A3 (ko) | 2016-09-09 |
PH12017501184A1 (en) | 2017-12-18 |
SG11201705194XA (en) | 2017-07-28 |
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