TW201014616A - Miglitol medicine composition - Google Patents

Abstract

The present invention relates to a Miglitol medicine composition and a manufacturing method thereof. The Miglitol medicine composition provided by the present invention is composed of: Miglitol of 100 parts of weight, bonding agent of 0.05-20 parts of weight, disintegrant of 15-60 parts of weight, diluent of 50-200 parts of weight, and lubricant of 0.05-20 parts of weight. The Miglitol medicine composition provided by the present invention features less number of constituent components, easy manufacturing, an effect of prolonged release to reduce the side effect of stomachache and gastronitestinal distension, and the same medical effect as the traditional medicines.

Description

201014616 IX. Description of the Invention: [Technical Field to Which the Invention Is Applicable] The present invention relates to a therapeutic composition and a green medicinal composition thereof. , species /, have the effect of reducing the role of abdominal steel [prior art]

With the social civilization, the living standards of ancient > sexually ill patients have increased rapidly, especially, the proportion of people and slow-moving, 3⁄4 ancient & 厶搂~, diabetes is the most threatening. In 2002, more than 10% of the elderly population aged between the ages of the elderly and the elderly were suffering from diabetes. In 1998, there were more than 8 diabetes patients in Taiwan. Ten thousand people, the cost of treating diabetes is more than 30 billion, accounting for 5% of health care medical expenses. 2〇〇1年 In the United States, 157 million people suffer from type 11 diabetes, which is the sixth leading cause of death in the United States. It consumes $44 billion in medical expenses and consumes 540 dollars.

Billion dollars of economic productivity. It is estimated that after 2, 1 year, it will become a high risk ^^, which will increase to 221 million. Miglit is a new type of diabetes-reducing drug developed by Bayer Pharmaceuticals in Germany in the early 1980s. The chemical name of the Miglit compound is [2 Min 311,411,58]-1-(2-hydroxyethyl)-2-(hydroxymethyl)-3,4,5-trihydroxypiperidine triol It is a deoxynojirimycin derivative. Miglitide is a new inhibitor of small intestinal α-glucosidase, which is suitable for the treatment of type 2 diabetes with diet control. The main mechanism of action is to reversibly inhibit α-glucosidase in the small intestine and reduce the breakdown of sugar into glucose. And can delay the absorption of glucose in the small intestine, and to reduce the increase in blood glucose after meals. 201014616 Miglit's plasma elimination half-life is approximately 2 hours. On average, after 2 to 3 hours of administration, the maximum plasma concentration of the plasma can be reached. After oral administration, more than 95% of the dose is discharged through the urine within 24 hours, but a small amount of unabsorbed drug is excreted by the feces. The main side effects of Miglit are gastrointestinal qi and abdominal pain. The original Glyset® product is known to be composed of nine components, and the product description shows that 962 patients have been found to have u.7% abdominal pain and 41.5°/ via clinical trials. For flatulence; in Diabetes Care, V17, N1, 1994: 20-29, the literature describes the treatment of MiGlite for 6 diabetes patients and found that • 50 mg of MiGlite has a side effect of flatulence. %, and the side effects of 100 mg of MiGlite are gastrointestinal flatulence, which means that the greater the dose, the greater the side effects. This side effect can easily cause discomfort to the patient. The rest are in Diabetes

Care V24 'N5 ' 2001 . 989-94 ; Diabetes Research and Clinical Practice ' 52, 2001 : 205-213 ; Journal of Clinical Endocrinology and Metabolism V83, N5, 1998 : 1515-1522 and other documents also present data to illustrate Glyset® products Although blood glucose can be effectively controlled, the side effect response data of this formula is also explained. In addition to the formulation of the GLYSET® product, there is a lactic acid orally disintegrating tablet for the treatment of type 2 diabetes, which is disclosed in the Continental Patent Publication No. CN 1615862A. This method is to change the release form of the dosage form. The main technical features are the composition and preparation method of the main drug and the excipient, wherein 'recipe one: 5 to 5 % of MiGlite, each part is 1 to 200 mg' and added Excipient formulations include: fillers 5 to 3 %, helper disintegrating agents to 30 to 30%, disintegrants 5 to 45%, and micronized gums (u to 3%: mixed after the powder is directly compressed into tablets) Temperature 18 to 26. (:, relative temperature control 45 to 65%; Formula 2: Miglilet 5 to 50 〇 / 〇, each tablet content is 1 〇 to 2 〇〇 mg, and first add filler 5 to 30 〇/〇, aiding disintegrating agent 5 to 3〇% mixed and then adding binder 5 to 15〇/〇 to make soft material 'and granulating, driers, granules, then adding disintegrant after 201014616 5 to 45% and other lubricants such as 0.1 to 3% of the lubricant, after mixing, tableting, the temperature between the tablets is 18 to 26. (: 'Relative temperature control 45 to Qing; 7 And the two formulations and processes can also add a sweetener 〇〇 5 to 1% or / and ^ 0. 〇 5% to 10%, and make an orally disintegrating tablet. The purpose of this invention ^ oral disintegration The tablets are not chewable, and the medicine is placed on the tongue. In the case of saliva (9) seconds, the small particles can be quickly dissolved. Therefore, it is beneficial to the elderly, swallowing difficulties or taking the patient in a special environment to take the patient's medication. , and sexual inhibition of heart (four) sugar _ 'reduction of the class in the stomach, intestinal degradation, = absorption from the effective riding of the urine patient blood sugar concentration peak, ^ control blood sugar. However, the shortcoming of the orally disintegrating tablet is collapse ', the side effects of stomach ups and downs are still obvious, causing discomfort and/or bitterness of the user = the adverse reactions of gastrointestinal tract in Miglitt can not be improved.,; GLYSET@ or the secret of the stomach (4) paste, two pull 梓 _ (four) side effects of the stomach tract therefore 'we look forward to the development of a new type of MiGlite doctor, reduce the dissolution in a short time after oral administration ' ' - after the set time to achieve the same dissolution rate as traditional medicine Medicine 1 in the content of the invention ΐ ΐ 2: missing 'the invention The purpose is to develop - a novel gastrointestinal = bell has a reduced rate of dissolution, to = traditional agent - like, can be achieved - after dissolution of 6g minutes, the dissolution rate is the same as the traditional agent, two: 4 mesh: = put the effect, music Physical dynamics data comparison has bioequivalence in efficacy (BE; 201014616)

Bioequivalence). To achieve the above object, the MiGlite pharmaceutical composition of the present invention comprises: parts by weight of milaginate; 〇. 〇 5 to 20 parts by weight of a binder; 15 to 6 parts by weight of a disintegrating agent; 50 to 200 a diluent of parts by weight; and a lubricant of 5 to 2 parts by weight, wherein the disintegrating agent is selected from the group consisting of microcrystalline cellulose, sodium cellulose, powdered cellulose, starch, and mixtures thereof. . Work Soil The binder referred to in the present invention is used to reduce the dissolution rate of the MiGlite 2 low. In the implementation secret, the aforementioned bonding ship includes but is not limited to -, syrup, methyl cellulose, propyl cellulose, (tetra) methyl cellulose, ^ based cellulose, guar gum, miscellaneous ribs, division, poly E women's money gathers B ^ Wei 旋 spin ride or its age. Difficult, aging age _ propyl sulphate invention system of the choice of disintegration agent, when the use of specific disintegration of the base age, fan impurities, impurities or powder also has a binder and thin _ Wei, can achieve delay collapse In addition to the ship's office, the type of the bulk type can be used for the first time (such as carboxy, sodium starch), which has a reduced dissolution rate to reduce various side effects; :i has the same dissolution rate as the traditional pharmaceutical agent to maintain the same Huazhong weight fraction of the two-dimensional Suina, Jiaohe methyl fiber fine, cross-linked polyethylene-converted _ joint == 201014616 t wave ^ Kelly potassium , pre-gelatinized starch, slow-drying base powder sodium, sodium alginate, = B @夂' temple powder or a mixture thereof. Preferably, the aforementioned disintegrating agent is carboxymethyl amide. The invention is referred to as a thin side which provides the mobility, lubricity, compressibility of the prepared composition (4), and the release property of the collateral with the aforementioned disintegrating agent. In one embodiment, the diluent comprises: 撼i, starch, pregelatinized starch, carbonic acid, calcium sulphate, glucosinolate, dextrose, dicalcium phosphate dihydrate , tricalcium phosphate, strontium magnesium, magnesium oxide, maltodextrin, mannitol, polydecyl propylene dihydrate 2, powdered cellulose, sodium carbonate, sorbitol, talc or its mouth. Preferably, the aforementioned diluent is mannitol. Lubricants, as they are referred to, reduce the adhesion to hard impurities after oral administration of the drug. In the implementation of the towel, the former (4) contains but not limited to, glyceryl palmitate stearate, magnesium oxide, Prosham polyethylene glycol, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, bismuth Preferably, the aforementioned lubricant is magnesium stearate. m. The oral pharmaceutical composition may be in the form of a tablet, a capsule or a powder. In the preferred embodiment, the invention comprises: lion weight parts of milaglin; 80 to the package of microcrystalline cellulose; The weight of the drug, to the severely wounded methylation powder sodium; and 410 parts by weight. More preferably, the aforementioned slip agent is a town of stearic acid. In the above preferred embodiment, the above-mentioned microcrystals can be used as the main diluent for the _, _, and _t == samples, and also have the function of disintegrating the 201014616 agent. However, since the disintegration rate of microcrystalline cellulose is very slow (3 〇 minutes), when combined with sodium carboxymethyl starch which is a rapid disintegrating agent (5 m in can be disintegrated), such a combination can be After oral administration, there is a reduced rate of dissolution at the beginning to reduce various side effects, but at! After the hour, it has the same effect as the traditional medicine: the speed of the valley to maintain the same effect. The pharmaceutical composition comprising the MiGril in the present invention can reduce abdominal pain, flatulence, etc. when administered orally to a patient in need of treatment for diabetes, and at the same time, can reduce manufacturing cost and reduce sales by reducing the addition of the excipient component. price. [Embodiment] The above-described preferred embodiments of the present invention are not intended to limit the modifications and minor modifications of the present invention in the scope of the present invention. The scope of the invention should be determined by the scope of the appended claims. The pharmaceutical composition for treating diabetes and or losing weight of the present invention comprises: 100 parts by weight of MiGlite; 5 to 20 parts by weight of a binder of 15 to 60 parts by weight of a disintegrating agent; 200 parts by weight of a diluent; and 〇〇5 to = parts by weight of a lubricant, wherein the disintegrating agent is selected from the group consisting of microcrystalline fibers" via methylcellulose, powdered cellulose, starch, and mixtures thereof. The binders, disintegrating agents, diluents and lubricants suitable for use in the present invention are as described. Preferably, the present invention may also be used for Miglitle, mannitol, hydroxypropylmethylcellulose and others. The excipient is wet-made together, and the formulation has the same effect as the original process by the conventional process. The propylmethylcellulose material, the agent, the dispersant, the thickener, and the film coating material are utilized. The characteristics of the preparation of the music into a mixed material sustained release tablets, sustained release capsules, hydrophilic gel sustained release = sustained release advantages of control agents can reduce plasma drug concentration fluctuations, reduce paper drug heart 201014616 J: efficacy, reduce adverse reactions. Miglit Pharmaceutical Group of the present invention The composition comprises: 8 to 120 parts by weight of the diluent in the sample; 20 to 50 parts by weight of the lining; to 1 part by weight of the propylmethylcellulose; 2 to 8 by weight; 1% nanocapsule; and 1 to 10 parts by weight of a lubricant. More preferably, methyl phyllo-oligosaccharide; the aforementioned m-stearic acid town. W replenishing agent is gans ❹ 述In the aspect, 'the aforementioned mannitol is the main and slightly sputum! The vitamin can be used as a disintegrating agent, a binder, and a diluent. In the dilute H sample, the main function of the aforementioned microcrystalline cellulose is ς = energy. _ 嶋 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四In the sample, the MiGlite pharmaceutical composition of the present invention can release slowly at this minute (release rate is slower than the original factory), and can produce side effects of flatulence and abdominal pain, but after dissolving 6 knives, Dissolved (four) and the original - like 'can achieve the effect of complete release, and can be found that the BE data is roughly the same as the traditional agent The same effect, therefore, has the same effect. The specific composition of the tablet has fewer types of components, shortens (4) and the time on the process, and prepares the customs, no special equipment and technical conditions. The technical characteristics of the soil invention are through various The parts by weight are formulated to achieve the advantages as described, and the preparation process is a conventional preparation process, such as, but not limited to, the following: Preparation method:: 100 g of Miglit 1G7g of mannitol, 5g dream! Propyl mercapto cellulose, 30g microcrystalline cellulose, mixing the above three components in a high shear mixer to form a powder mixture, and then adding water or alcohol to the powder 11 201014616 it The alcohol or the nickname is dissolved to form a granule mixture, and dried at a temperature of yu lion C to obtain dry granules, which are sieved with magnesium mound (10) ί i particles. The granules of about 5 s grades of methyl sulphate and about 1% of stearic acid are added to the pulverized particles, and then uniformly mixed, and the granules after the pulverization are compressed to prepare a troche. , alcohol, f 2: 100g of MiGlite, 85g parts by weight of mannose, 2 (the trowel, Kunming Μ mixed the above two components to form a powder mixture. Connected (4) and 35g of microcrystalline fiber _ join Mix water or alcohol "ethanol, n-propanol or isopropanol to dissolve evenly, then propyl group in powder. The solvent of the cellulose is prepared to form a wet granule mixture, and dried at a temperature of J) C to 1 GG ° C to obtain dry granules, which are removed by a sieve = 1$. 6 g of the solution base powder was applied to 4 g of stearic acid to record the sieved particles, which were then uniformly mixed, and the pellets after the grinding were compressed to prepare a tablet. Method 3: 100 g of Miglilet, 80 g of mannitol, and 45 g of glutamic acid are mixed in the high shear mixing 11 to form a powder. Then add 20g of propylmethylcellulose to water or alcohol (such as B-trans, η-alcohol or isopropanol) and mix and dissolve evenly. Add the powder containing interesting propyl carbaryl to the powder. The surface-aged material was prepared and dried at a temperature of = to 100 ° C to obtain dry granules which were subjected to a sieve removal by a sieve. 5 g of magnesium stearate was added together to the milled granules, and the mixture was uniformly mixed. Then, the milled granules were allowed to shrink to form a bond. A preparation method 4: 100 g of Miglit, 89 g of glycerol was mixed in the south shear mixer to form a powder mixture. Mixing the propyl f-based cellulose of the female with 3Gg of the microcrystalline cellulose into water or an alcohol (such as ethanol, η-propanol or isopropanol) to dissolve the homogeneous liquid A mixture of wet granules was prepared in the powder and carried out at 5 Torr. 〇到1〇〇 It 12 201014616 It is further sieved with r to remove large particles =: Then proceed with the preparation method five: 100g of Megley microcrystalline cellulose, in high cut, Ύώ, θ people $心甘路楯知与45g "Shipping material from (four) miscellaneous, silk (four) floating liquid type spray drying under the dry button, the material used _ then mixed mixed sentence, New Zealand will be crushed particles after the two (2) agent. Reference preparation method 6 is: mixing the propyl fluorenyl cellulose of hydrazine with % microcrystalline cellulose = human water or lysine (such as ethanol, n__ or iso (tetra)) to dissolve the suspension liquid evenly to the secret of lGGg Lit powder. Add 90g of ganol to the high shear mixer and mix it with the above-mentioned floating liquid spray to the green stalk to prepare the wet granules, and dry at 5 (rc to (10).c to obtain dry granules. And sifting it with a sieve to remove large particles. About 3 g of carboxymethyl phosphatide and about 10 g of magnesium stearate are added together to grind the granules, followed by mixing uniformly, and then grinding the granules The tablet can be prepared by compression. Preparation method VII. 3 g of hydroxypropyl fluorenyl cellulose is added to water or an alcohol (such as ethanol, η-propanol or isopropanol) and the mixture is uniformly sprayed to the suspension. 100g of MiGlite powder. Add 13% mannitol and 15g of microcrystalline cellulose to the high shear mixer and spray the suspension onto the MiGlite to prepare the wet granules. Drying is carried out at a temperature of from 50 ° C to 10 ° C to obtain dry granules. The granules are sieved to remove large granules. lg ^ 13 201014616 曱, sodium starch and about lg of magnesium stearate Co-add the pulverized granules together, then mix them evenly, then grind them The granules can be compressed to form a tablet. Preparation method 8: 100 g of Miglit, 89 g of mannitol, 2 g of hydroxypropyl decyl cellulose, 5 g of sodium carboxymethyl starch, 3 The microcrystalline cellulose of 〇g is mixed with the above five components in a shearing shear mixer to form a powder mixture, and then a solvent of water or an alcohol such as ethanol, η-propanol or isopropanol is added to the powder to form Wet the mixture of particles and carry out drying at 50 ° (: to 1 〇〇 to obtain dry granules, which are sieved to remove large particles. 5 g of carboxymethyl silicate and sodium powder are hardened The magnesium sulphate is added to the pulverized granules together, and then uniformly mixed, and then the pulverized granules are compressed to prepare a troche. Preparation Method 9: 50 g of MiGlite, i 〇〇g of mannose Alcohol, i〇g of hydroxypropyl decyl cellulose, 30 g of microcrystalline cellulose, 5 g of sodium carboxymethyl starch, 5 g of magnesium stearate, mixed with the above six components in a high shear mixer to form a Prepare a powder mixture. Put the mixture into a dry granulator to dry the granules to form irregular shapes. Granular material, and finally the granules are compressed into ingots. Preparation Method 10: 50 g of MiGlite, 54 g of mannitol, 2 g of propylmethylcellulose, 15 g of microcrystalline cellulose, mixed in high shear The mixture is prepared by mixing the above four components to form a powder mixture. The mixture is placed in a dry granulator to dry the granules to form irregular granular materials, and then 2 g of methylidene powder and 2 g of magnesium stearate are added. Mixing with the irregular granular material, and finally compressing the mixed particulate matter into an ingot. Preparation Method 11: 25 g of Miglit, 50 g of mannitol, 5 g of propylmethylcellulose , lg of sodium carboxymethyl starch, 15 g of microcrystalline cellulose, prepared by mixing the above five components in a high shear mixer to form a powder mixture. The mixture is placed in a dry granulator to dry the granules to form an irregular granular material. Then, lg of sodium carboxymethyl starch, 2 g of magnesium stearate and irregular particulate matter are uniformly mixed, and finally mixed. The particulate matter is compressed into 14 201014616 keys. It is a powder of Lit, I wish mannitol, lg lg magnesium stearate, in high cut, 3 into = 曰, · 素素, 1g of renegade methyl condensate, mixture ^ thief into a powder Ingredients, 活性 active ingredients, nectar, lying methyl fiber -, two. Combination of broad and hard fats (4) Drying and wetting of the lyophilized granules can be used to form tablets or capsules. The tablets or capsules are bio-use, and the liquid is in the liquid.

The MiGlite pharmaceutical composition of the present invention in which four different components are listed in Table 1 can be produced by any of the procedures described above. Table 1 Ingredients Group I Group 2 Group 3 Group IV Millipl 100 100 50 25 Mannitol 107 70 100 50 Hydroxypropyl Methyl Vividin 5 20 10 5 Microcrystalline Weaving 30 45 30 15 Carboxymethyl starch sodium 5 8 5 2 1 Magnesium stearate 3 7 5 2 15 201014616 Total (mg) I. 250 250 200 99 Special pharmaceutical composition Bio-use 疳 疳 本 本 本 本 本 本 本 本Bioavailability will be compared to GLYSET®. (10) Solitary 8 is manufactured by Bayer Co., Ltd., which has been invented by the company. In addition to the active ingredient, Miglit, it contains inactive starch, microcrystalline cellulose, magnesium stearate, and hydroxypropylmethyl. Cellulose, polyethylene glycol, titanium oxide, polysorbate 8 oxime, and the like. .米遮jj特边_乐 composition of the internal test pharmacokinetics I disk (10) > experimental test method for 'let 16 subjects in the oral administration of MiGlite just ten hours after taking the drug still need to fast 4 hours, carry out a random, single-agent Dong" two-way X-fork method.

e^l.〇^e,w.5^e,.2.〇^,2.5,^.3.〇lt35I, 5.〇 hours, 60 hours, 8 hours, ιο hours, i2 small 3 Plasma samples were analyzed for pharmacokinetic analysis. The resulting table 2 items Tmax (hr) 1—T-/2 (hr) -------___ c , max (ng/ml) ------ AUC〇-+ j (hr · ng/ml) 1 1.— AUC〇—〇〇 (hr · ng/ml) GLYSET® 2.8+0.7 2.1±0.3 1797+418 —-------— 9875±2311 10070+2335 Example 1 2.8±l.〇2.0+0.2 Π54±464 ··— 965612205 9827+2244 . .1 From the above table, the pharmacokinetic parameter τ of Φ *Jr «fc ua a --- ——___1 ...small slogan|data difference with GLYSET® products. Wei 彳 彳 ί ί G—1, tear “There is no significant difference in the income ,, so it is evaluated that the two have the same 16 201014616 body equality. Example 3· The dilution ratio of the different concentrations of the solution from the first plot of 0.1Ν Ηα, the second plot of pH 4.5 Acetate Buffer, and the third plot of pH 6.8 Phosphate Buffer is shown in Figure 1. 'The MiGlite pharmaceutical composition of Example 1 of the present invention has a lower elution rate between 10 and 30 minutes compared to GLYSET®, but the dissolution rate of #GLYSET® is consistent after 6 minutes. According to the above pharmacokinetic data, the two are not only in the raw The effect of the degree of utilization is comparable, and the number of elution rates in vitro dissolution shows that the embodiment of the present invention has a lower elution rate in the first 3 minutes, so that when the drug is released into the stomach, it will not be caused by the drug. Excessive release causes side effects of abdominal pain and flatulence in a short period of time, thereby reducing the suffering of patients who take this medicine. _ The fourth figure shows the MiGlite medical group & The concentration of jk with GLYSET is clear. The results show that the #格lite pharmaceutical composition of the present invention has the same bioavailability as GLYSET®. » The application of the example 4·Miglit is to be implemented in accordance with the present invention. The MiGlite pharmaceutical composition of Example 1 was stored for one year, and its content of Miglilet was measured periodically. The results are shown in Table 3. 'Table 3 Time January January February March April June September December content (mg) 101.2 101.1 100.9 100.6 100.1 100.9 100.6 100.2 a _ 17 201014616 The table can be seen that the MiGlite pharmaceutical composition of the present invention is prepared as a 4 fulfilment of female surname, 仃 仃 仃 test Test, the results show that the save was saved One year \ : two, the inclusion of the composition did not significantly decrease, so the formulation of the MiGlite medical composition of the present invention is young in the medicine. Special medical test

In the clinical trial of the MiGlite pharmaceutical composition of the present invention, the side gamma improvement of the gastric tract is observed. In this clinical trial, the mites of the present invention == and 】, another component of the class Acarb〇se is used for efficacy and safety. For example, the security differences are shown in Table 4 and Table 5.

Acarbose and Mirius are related to small intestine alpha glucose crane inhibitor, which is suitable for the treatment of π-face urinary disease with diet control. The main (four) _ mechanism is to reversibly inhibit α-glucose in the intestinal tract; Glucose' can delay the absorption of small intestines (four), and the rate of blood sugar rises to the south after the meal. Both of them are used for the treatment of patients with diabetes. According to GLYSET® products, the incidence of side effects in the gastrointestinal tract is very high. The Acarbose of the flatulence is higher than 178 times of the miglitol, and the abdominal pain is higher than the Acrobose. 1.62 times.

*4 -Acarbose ^ GLYSEI\|^B^ The basis of the book is abdominal pain, flatulence, Acarbose 19%, 74% Migliol, 11.7%, 41.5%. The clinical trial of the MiGlite pharmaceutical composition of Example 1 of the present invention was carried out. Forty-seven patients underwent double-blind, single-center, effective 201014616 drug control, randomized parallel trials for a total of 14 weeks. The test method was to take one 50mg acarbose capsule and one 50mg miglitol placebo together with the meal. After the week, increase the dose to three meals a day with a 5〇11^ acrabose capsule and a l〇〇mg miglitol placebo for 10 weeks. The results are shown in Table 5. According to the data, the flatulence acrob〇se is 2.87 times higher than the miglitol's abdominal pain acrab〇se is more than 4.2 times, and other side effects such as abdominal diseases, kidney and urinary diseases, bladder stones, ureteral stones, dysuria, renal colic ' These side effects are relatively lower than those of acarbose. Table 5 - Data of clinical trials of Acarbose and the MiGlite pharmaceutical composition of Example 1 of the present invention

Miglitol (%) Acarbose (%) Abdominal pain 0.0 % 4.2 % Upper abdominal disease 0.0 % 4.2 % Flatulence 8.7% 25.0 % Frequent bowel movements 4.3 % 4.2 % Bladder stones 0.0 % 4.2 % Ureteral stones 0.0 % 4.2 % Urinary dysfunction 0.0 % 4.2 % renal colic 0.0% 4.2% = in the in vitro dissolution of the MiGril (mig) in the present invention, the rate of release in the first 30 minutes is higher than GLYSET (g^, compared with m (f) in Table 5 The invention of the present invention is based on the fourth aspect of the present invention. The trend of side effects makes the stomach discomfort less obvious. In summary, the pharmaceutical composition of the present invention, the MiGlite tablet, has in vitro dissolution data, the 10th. The dissolution rate to 30 minutes is slower than that of GLYSET®. Therefore, when the drug is released slowly during the stomach, the patient can slow down the side effects of abdominal pain and flatulence; the in vivo test is tested by bioavailability. It is known that the pharmacokinetics of the two organisms are equivalent, and the therapeutic effect is the same, and the occurrence rate of the known brake action in the fern bed test of 47 cases is slowed down. Scale and process Time, in terms of preparation, the method is simple, and no special equipment and technical conditions are required. Other implementations All of the ship systems disclosed in the present invention can combine the lungs and the way. The features disclosed in the present specification can use the same, equal or similar purpose. The features disclosed in this specification are one of a series of equal or similar features, except for the particular statement. 瘫4 - According to the disclosure of this specification, the technical field is reduced. r, the basic characteristics of the invention, the financial law and the situation are appropriately changed and modified without departing from the spirit and scope of the invention. Therefore, other implementation aspects are also included in the scope of the patent application. ', 20 201014616 Brief Description of the Invention The first figure is a comparison of the dissolution ratio of 100 mg of the MiGlite pharmaceutical composition of the present invention and 100 mg of GLYSET® in a 0.1 N hydrochloric acid solution. The second figure is i〇〇mg in acetic acid buffer of pH 4.5. The dissolution ratio of the Miglit pharmaceutical composition and 100 mg of GLYSET®. The third figure is the pH of 6.8 in the sulphate buffer. Pharmaceutical composition from the ratio of the dissolution lOOmgGLYSET® FIG. Split serum MIG fourth graph lOOmg pharmaceutical compositions of the present invention with reference to FIG lOOmgGLYSET® concentration ratio of 21

Claims (1)

201014616 X. Patent application: L-type Miglilite pharmaceutical composition comprising: 100 parts by weight of Miglitide; 〇.〇 5 to 20 parts by weight of binder; . Μ曰_ = * to 6 The disintegrating agent is selected from the group consisting of cellulose, ketone fiber powder, powdered fiber, starch and 50 to 200 parts by weight of a diluent thereof; and 〇.〇5 to 20 Parts by weight of lubricant. 2. The pharmaceutical composition according to claim 1, which comprises: 100 parts by weight of MiGlite; 1 to 10 parts by weight of a binder; and a collapse of 5G parts by weight, (4) It is selected from the group consisting of methyl fiber tumbling, powdered cellulose, starch and 80 to 120 parts by weight of a diluent thereof; and 1 to 10 parts by weight of a lubricant. • Person! (4) Please select the 1 drug composition in the first item, including the starch slurry, syrup, methyl cellulose, hydroxypropyl cellulose, hydroxyl cellulose, ethyl cellulose, guar gum. , magnesium aluminum silicate, gelatin, polystyrene, polystyrene, hydroxycane or a mixture thereof. 4. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises a second disintegrating agent in an amount of from 1 to 1 part by weight. The medicinal composition described in the fourth aspect of the patent, wherein the aforementioned one-two spurs H-brown, each, (four) base fiber, hetero-phosphorus oxide, father-linked methyl cellulose, cross-linking Cellulose dance, cross-linked polyethylene, methylcellulose, pollackin unloading, pregelatinized starch, slow methyl methoxide powder, 22 201014616 sodium alginate, sodium starch glycolate or mixtures thereof . 6. The pharmaceutical composition according to claim 4, wherein the disintegrating agent is 2 to 8 parts by weight. The pharmaceutical composition according to claim 1, wherein the diluent comprises: lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate sugar, glucose binder, dextrin, Dextrose, dicalcium phosphate dihydrate, tricalcium phosphate, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethyl propyl Sour vinegar, chlorinated, powdered cellulose, gasified sodium, sorbitol mixture. 4. The pharmaceutical composition according to the invention of claim 5, wherein the lubricant comprises: hard fat lysine, manns brown followed by hard fat, oxidized town, and poloxamer, polyethylene glycol , polyethylene glycol, sodium benzoate, laurel ^ sodium sulphate, sodium stearyl sulphate, stearic acid, talc, stearic acid, stearic acid, tert-butyl diacid, hydrogen sloping oil The pharmaceutical composition of the hydrogen domain hiding, oil-eliminating or mixing thereof, which is an ingot 9. The dosage, capsule or powder form of the patent application. 80 to 12 G parts by weight of mannitol; methyl cellulose; ^ 1 part by weight of sodium starch sodium; 1 to 1 part by weight of a lubricant; and 20 to 50 parts by weight of microcrystalline cellulose. twenty three