CN106880595A - Unformed Yi Palie net a kind of solid dispersions and preparation method thereof - Google Patents
Unformed Yi Palie net a kind of solid dispersions and preparation method thereof Download PDFInfo
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- CN106880595A CN106880595A CN201510910666.5A CN201510910666A CN106880595A CN 106880595 A CN106880595 A CN 106880595A CN 201510910666 A CN201510910666 A CN 201510910666A CN 106880595 A CN106880595 A CN 106880595A
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- palie
- solid dispersions
- pharmaceutic adjuvant
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
Abstract
A kind of unformed Yi Palie net solid dispersions and its manufacture method, it includes pharmaceutic adjuvants of the Yi Palie only with two or more, and Yi Palie is only 1 with the weight ratio of whole pharmaceutic adjuvants:0.1 ~ 100, wherein, the Yi Palie in the solid dispersions is only unformed shape, and the characteristic peak without the net crystal of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted in the X ray Powder Diffraction patterns of the solid dispersions.Yi Palie of the invention net solid dispersions stability and favorable dispersibility, increased the net dissolution rates of Yi Palie, it is more beneficial for improving the absorption of the bioavilability and body of pharmaceutical preparation to medicine, under the conditions of accelerated test, good physical stability and chemical stability can be kept.The preparation method of unformed solid dispersions of the invention is simple to operate, convenient to separate, with low cost, favorable reproducibility, it is easy to accomplish, it is adapted to industrialized production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of unformed Yi Palie net solid dispersions and its preparation
Method.The invention further relates to a kind of Pharmaceutical composition, said composition is comprising amorphous state Yi Palie net solid dispersions and extremely
Few a kind of pharmaceutically acceptable auxiliary material, for treating diabetes.
Background technology
Yi Palie is net（Emagliflozin）, trade name Jardiance, chemical name is：(1S) -1,5- dehydrations -1-C- [the chloro- 3- of 4- [[4- [[(3S)-tetrahydrochysene -3- furyls] epoxide] phenyl] methyl] phenyl]-D-Glucose alcohol, its structure such as formula
（I）It is shown：
Formulas I
Yi Palie is to be treated to use by the type ii diabetes of German Bo Lingeyinggehan companies and Lilly Co., Eli.'s cooperative research and development only
Medicine.Yi Palie was approved by the FDA in the United States listing on 1st only on May 22nd, 2014 in the granted listing of European Union in August in 2014.
It was predicted that future 10-20 diabetes number of patients has first of disease shelter, suffer to the year two thousand twenty diabetes mellitus in China
Person's number will be up to 1.5 hundred million, be the most country of global diabetic.Global diabetes Market total sales volume is more than 350
Hundred million dollars, diabetes mellitus in China market scale is up to 15,000,000,000.Yi Palie is the 3rd, the whole world treating diabetes novel targets of listing only
Sodium glucose co-transporter 22（SGLT-2）Inhibitor, is conducive to the Regulation of blood glucose of 2 diabetes mellitus types, and will not make
Into hypoglycemia, and there is certain fat-reducing effect, for patient provides preferably selection.
Yi Palie net deposits are in various crystal formations.Chinese patent CN101155794 discloses a kind of net crystal formations of Yi Palie.It is Chinese special
Sharp CN104788438 pages discloses a kind of net crystal formation Form B of Yi Palie.Indian patent IN 2013MU01985 disclose one
The Yi Palie of kind of unformed shape is net and a kind of Yi Palie containing unformed shape is net and a kind of solid dispersions of macromolecular material.
The solid forms of medicine directly affect the rate of dissolution of bulk drug, the dissolution rate of preparation and bioavilability, in order to
The bioavilability of medicine is improved, consumption is reduced, is reduced toxic and side effect, it will usually develop the new solid forms of medicine, therefore,
Develop the solid form that the drug solubility is more preferable, bioavilability is higher and just seem necessary.
The solid forms of medicine in addition to crystalline state, also unformed state, the unformed state of medicine is used as solid matter
A kind of specific form, there is important purposes in medicine preparation.Normally due to the orderly and periodicity of amorphous material molecule is arranged
Row, reduce the energy of intermolecular interaction, and energy is relatively low, and the molecule of unformed shape is in height disordered state, material
Surface free energy it is bigger, the molecule in solid matter has energy higher compared with the molecule in crystalline solid material, it is easier to point
Dissipate, increase its dissolution rate, improve the bioavilability of medicine.Unformed shape medicine not only can be widely applied to pharmaceutical preparation
In, and can be made with excellent product by multiple technologies means and the stability of method raising unformed shape medicine
The medicine of matter.
It is net and a kind of containing unformed shape that indian patent IN 2013MU01985 disclose a kind of Yi Palie of unformed shape
Yi Palie is net and a kind of solid dispersions of macromolecular material.A kind of medical high-molecular additive is comprised only in the solid dispersions.
It is not ideal, the generally change of gained solid dispersions to the peptizaiton of medicine due to single medical high-molecular additive
Learning stability and physical stability can all be deteriorated.So to obtain unformed drug molecule and make it stable past in unformed state
Toward the amount needed than larger pharmaceutic adjuvant.Pharmaceutical preparation must use various pharmaceutic adjuvants, and auxiliary material total amount also has certain limitations,
As certain single auxiliary material large usage quantity when, can also bring certain difficulty to the exploitation of pharmaceutical formulation.In addition, for only adding
Enter a kind of separation of the solid dispersions of high polymer adjuvant and cannot get segregative solid.If using two or more
Pharmaceutic adjuvant, can often improve the physical state of solid dispersions, make it easier to separate, and be more beneficial for large-scale industrialization
Production.
Because existing amorphous state Yi Palie net not enough and unformed active constituents of medicine is in terms of pharmaceutical preparation
Good application prospect, finds that new unformed Yi Palie is net and preparation method thereof just to seem very necessary.
The content of the invention
It is an object of the invention to provide a kind of Yi Palie only with the solid dispersions of pharmaceutic adjuvant and preparation method thereof, obtain
The Yi Palie of the unformed shape of stability and favorable dispersibility only with the solid dispersions of pharmaceutic adjuvant, increased Yi Palie net
Dissolution rate, the preparation method is not limited by drying process, is not also limited by solvent species and quantity of solvent, easy to operate, into
This is cheap, it is easy to accomplish, it is capable of achieving industrialized production.
In order to achieve the above object, technical scheme is as follows：
A kind of Yi Palie only with the solid dispersions of pharmaceutic adjuvant, the solid dispersions comprising Yi Palie only with two kinds or two kinds with
On pharmaceutic adjuvant, Yi Palie is only 1 with the weight ratio of whole pharmaceutic adjuvants:0.1 ~ 100, wherein, in the solid dispersions
Yi Palie only be unformed shape, in the X-ray powder diffraction spectrum of the solid dispersions, deduct pharmaceutic adjuvant background
Without the characteristic peak of Yi Palie net crystal behind peak.
Further, at least one in the pharmaceutic adjuvant is selected from diluent, lubricant, adhesive, disintegrant, surface work
At least one in property agent, filmogen, coating material and capsule material.
Preferably, at least one in the pharmaceutic adjuvant is selected from HPMC, hydroxypropyl cellulose, poly- dimension
Ketone, polyethylene glycol, ethyl cellulose, microcrystalline cellulose, liposome, methacrylic acid copolymer, polyvinyl acetate, carboxymethyl second
Base cellulose, carboxymethylcellulose calcium phthalic acid ester, hydroxypropyl methylcellulose phthalate, HPMC vinegar
Acid esters succinate, polyacrylic resin, carbopol, alginates, carragheen, caprolactone, natural gum, polyvinyl alcohol,
Pregelatinized starch, crosslinked starch, sodium carboxymethyl starch, dextrin, PEO, shitosan, chitosan, collagen and ring
At least one in dextrin.
Yi Palie of the invention only with the preparation method of the solid dispersions of pharmaceutic adjuvant, comprise the following steps：
1) Yi Palie is mixed with two or more pharmaceutic adjuvant only, is heated to pharmaceutic adjuvant melting；Wherein, Yi Palie
Only it is 1 with the weight ratio of whole pharmaceutic adjuvants:0.1~100；
2) cooled down after being well mixed, mixture is crushed, the Yi Palie for obtaining unformed shape disperses with the solid of pharmaceutic adjuvant only
Body.
Further, at least one in the pharmaceutic adjuvant is selected from diluent, lubricant, adhesive, disintegrant, surface work
At least one in property agent, filmogen, coating material and capsule material.
Preferably, step 1）Described in pharmaceutic adjuvant at least one to be selected from HPMC, hydroxypropyl fine
Dimension element, PVP, polyethylene glycol, ethyl cellulose, microcrystalline cellulose, liposome, methacrylic acid copolymer, poly-vinegar acid second
Alkene, carboxymethylethylcellulose, carboxymethylcellulose calcium phthalic acid ester, hydroxypropyl methylcellulose phthalate, hydroxypropyl
Methylcellulose acetate succinate, polyacrylic resin, carbopol, alginates, carragheen, caprolactone, tree
Glue, polyvinyl alcohol, pregelatinized starch, crosslinked starch, sodium carboxymethyl starch, dextrin, PEO, shitosan, chitosan,
At least one in collagen and cyclodextrin.
The present invention provide another kind Yi Palie only with the preparation method of the solid dispersions of pharmaceutic adjuvant, including walk as follows
Suddenly：
1) Yi Palie is mixed in a solvent with two or more pharmaceutic adjuvant only, mixing temperature is -50 ~ 150 DEG C,
The solution or suspension of and pharmaceutic adjuvant net containing Yi Palie are formed, wherein, Yi Palie is 0.001 with the weight ratio of solvent only ~
100:1, Yi Palie is only 1 with the weight ratio of whole pharmaceutic adjuvants:0.1~100；
2) removing step 1）Solvent in the solution or suspension that obtain, obtains the Yi Palie of unformed shape only and pharmaceutic adjuvant
Solid dispersions.
Further, at least one in the pharmaceutic adjuvant is selected from diluent, lubricant, adhesive, disintegrant, surface work
At least one in property agent, filmogen, coating material and capsule material.
Preferably, step 1）Described in pharmaceutic adjuvant at least one to be selected from HPMC, hydroxypropyl fine
Dimension element, PVP, polyethylene glycol, ethyl cellulose, liposome, methacrylic acid copolymer, polyvinyl acetate, sodium carboxymethylethyl
Cellulose, carboxymethylcellulose calcium phthalic acid ester, hydroxypropyl methylcellulose phthalate, HPMC acetic acid
It is ester succinate, polyacrylic resin, carbopol, alginates, carragheen, caprolactone, natural gum, polyvinyl alcohol, pre-
Gelling starch, crosslinked starch, sodium carboxymethyl starch, dextrin, PEO, shitosan, chitosan, collagen and ring paste
At least one in essence.
Also, step 1）The solvent is selected from containing less than 12 alcohols, phenols, ethers, halogenated hydrocarbons, ketone, the aldehyde of carbon atom
At least one in class, nitrile, acid amides, sulfone, sulfoxide, carboxylic acid and water, step 2）The method for removing solvent includes：Evaporation, vacuum
Evaporation, spray drying, freeze-drying, hot-melt extruded, filtering, centrifugation or agitated thin film.
Present invention also offers a kind of Pharmaceutical composition, the Pharmaceutical composition contain unformed Yi Palie it is net and two kinds or
Two or more pharmaceutically acceptable auxiliary materials, at least one in the pharmaceutic adjuvant is selected from diluent, lubricant, bonding
At least one in agent, disintegrant, surfactant, filmogen, coating material and capsule material.
Further, at least one in the pharmaceutic adjuvant in above-mentioned Pharmaceutical composition is selected from HPMC, hydroxypropyl
Base cellulose, PVP, polyethylene glycol, ethyl cellulose, microcrystalline cellulose, liposome, methacrylic acid copolymer, poly-vinegar acid
Ethene, carboxymethylethylcellulose, carboxymethylcellulose calcium phthalic acid ester, hydroxypropyl methylcellulose phthalate, hydroxyl
Third methylcellulose acetate succinate, polyacrylic resin, carbopol, alginates, carragheen, caprolactone,
Natural gum, polyvinyl alcohol, pregelatinized starch, crosslinked starch, sodium carboxymethyl starch, dextrin, PEO, shitosan, chitin gather
At least one in sugar, collagen and cyclodextrin.
The present invention also provides a kind of Pharmaceutical composition, and said composition contains net solid dispersions of unformed Yi Palie and at least
A kind of pharmaceutically acceptable auxiliary material.Solid dispersions in said composition include unformed Yi Palie only and at least two pharmacy
Upper acceptable auxiliary material.
Further, said composition is used to prepare antidiabetic medicine.
Yi Palie of the invention only with the solid dispersions of pharmaceutic adjuvant, radiated using Cu-K α, the X- represented with spending 2 θ is penetrated
The characteristic peak of the background peaks without the net crystalline states of Yi Palie of pharmaceutic adjuvant is deducted in line Powder Diffraction pattern, shows that Yi Palie is nothing only
Stabilized condition.The net crystalline states of Yi Palie are generally used in the prior art, have no the report of its unformed shape.Normally due to crystalline state
The orderly and periodic arrangement of material molecule, reduces the energy of intermolecular interaction, and energy is relatively low, and of the invention according to handkerchief
Row are unformed shape only, and molecule is in height disordered state, and the surface free energy of material is bigger, and the molecule in solid matter is more brilliant
Molecule in state solid matter has energy higher, it is easier to disperse, and increases its dissolution rate, improves the net biological utilisations of Yi Palie
Degree.
The present invention is net and after pharmaceutic adjuvant is well mixed by Yi Palie, use " solid dispersion " method, by pharmaceutic adjuvant
Polymer network structure drug molecule is intercepted, suppress crystallization generation, make its keep dispersion and unformed state.The present invention
In pharmaceutic adjuvant select two or more pharmaceutic adjuvant.Compared with single auxiliary material, various mutual compatibilities of pharmaceutic adjuvant,
Dispersion can be preferably played, drug molecule is intercepted and suppresses the effect of crystallization.For example, having multiple hydroxyls only for Yi Palie
This design feature, the present invention in pharmaceutic adjuvant introduce polyhydroxy alcohols, between drug molecule and the hydroxyl of alcohols easily
Hydrogen bond is formed, stronger interaction is produced, decentralization of the medicine in auxiliary material can be strengthened, and can preferably suppress drug molecule
Crystallization.Additionally, various pharmaceutic adjuvants can also play different effects in pharmaceutical preparation, be conducive to opening for pharmaceutical preparation
Hair.Present invention use is widely used, the pharmaceutic adjuvant that cheap, dissolubility is good, and these pharmaceutic adjuvants mix only with Yi Palie,
Coordinating the technologies such as evaporation, spray drying, freeze-drying and hot-melt extruded can obtain the net amorphous forms of Yi Palie, increase this
The stability of Yi Palie in the invention net solid dispersions of Yi Palie net unformed shape.Gained solid physical state is good,
It is easily isolated.
The present invention select pharmaceutically widely used, cheap auxiliary material, obtain Yi Palie only with pharmaceutic adjuvant
Solid dispersions, it is easy to develop pharmaceutical formulation, preparation method of the invention is not limited by drying process, does not also receive solvent species
With the limitation of quantity of solvent, it is easy to operate, be easy to separate, it is with low cost, it is easy to accomplish, be capable of achieving industrialized production.
Compared with prior art, the beneficial effects of the invention are as follows：
1) unformed Yi Palie prepared by the present invention has height with the solid dispersions of two or more pharmaceutic adjuvant only
Degree dispersiveness and stability, various pharmaceutic adjuvants can draw wrong conclusions by false analogy different effects in pharmaceutical preparation, be conducive to opening for pharmaceutical formulation
Hair.After solid pharmaceutical preparation is made, the degree of scatter of drug particle can be made by being disintegrated more preferably, dispersion and dissolution rate faster, have
Beneficial to the absorption of medicine.Therefore, the dissolution rate of unformed state medicine substantially increases, and is more beneficial for absorption of the body to medicine,
The bioavilability of medicine is improved, allows medicament to preferably play clinical disease treatment effect.
2) Yi Palie of unformed state of the invention does not receive drying with the preparation method of the solid dispersions of pharmaceutic adjuvant only
The limitation of process, is not also limited by solvent species and quantity of solvent, easy to operate, is easy to separate, with low cost, it is easy to accomplish,
It is capable of achieving industrialized production.
3) Yi Palie of unformed state prepared by the present invention is only with the solid dispersions of pharmaceutic adjuvant in high temperature, high humidity
Under the conditions of, relevant material crystallizes precipitation without Yi Palie only without significantly changing；Under the conditions of accelerated test（40 ± 2 DEG C, humidity 75%
±5%）, relevant material crystallizes precipitation without Yi Palie only without significantly changing, and the Yi Palie of unformed state of the invention is only and medicine
Good physical stability and chemical stability can be kept with the solid dispersions of auxiliary material, it will have broad application prospects.
Brief description of the drawings
Fig. 1 is net and hydroxypropyl cellulose SSL and PVP K30 the solids of the unformed Yi Palie of the embodiment of the present invention 1
The X-ray powder diffraction figure of dispersion.
Fig. 2 is for the unformed Yi Palie of the embodiment of the present invention 12 is net and Macrogol 4000 and Eudragit L 100
The X-ray powder diffraction figure of solid dispersions.
Specific embodiment
Below in conjunction with specific embodiment, the invention will be further described, but protection scope of the present invention does not receive following implementation
The limitation of example.
X-ray powder diffraction figure of the present invention is gathered on Ultima IV x-ray diffractometers.It is of the present invention
X-ray powder diffraction method parameter it is as follows：
X-ray powder parameter：Cu-Kα
Kα（）：1.5418
Voltage：40 kilovolts
Electric current：40 milliamperes
Divergent slit：Automatically
Scan pattern：Continuously
Sweep limits：From 2.0 to 60.0 degree
Sampling step length：0.0200 degree
Sweep speed：60 degrees/min
Embodiment 1
Yi Palie is net（50 milligrams）, hydroxypropyl cellulose SSL（50 milligrams）And PVP K30（50 milligrams）It is added to methyl alcohol
（800 microlitres）In, it is molten clear to be heated to 60 DEG C of stirrings, is evaporated in vacuo and removes solvent, obtains white powdery solids, i.e., it is unformed according to
Handkerchief row only with hydroxypropyl cellulose SSL and the solid dispersions of PVP K30.The X-ray powder diffraction figure of the solid dispersions
As shown in figure 1, in X-ray powder diffraction figure deduct pharmaceutic adjuvant background peaks after the characteristic peak without the net crystal formations of Yi Palie.
Embodiment 2
Yi Palie is net（50 milligrams）, polyacrylic resin Eudragit L100（50 milligrams）And Macrogol 4000（200 millis
Gram）It is dissolved in ethanol（600 microlitres）And water（600 microlitres）In, it is uniformly mixed at -40 DEG C, it is evaporated in vacuo and removes solvent, obtain
To white powdery solids, i.e., unformed Yi Palie only with polyacrylic resin Eudragit L100 and Macrogol 4000
Solid dispersions.It is net without Yi Palie after the background peaks of deduction pharmaceutic adjuvant in the X-ray powder diffraction figure of the solid dispersions
The characteristic peak of crystal formation.
Embodiment 3
Yi Palie is net（2 grams）, dextrin（2 grams）And PEG 8000（10 grams）Add water（300 milliliters）In, it is heated to 60 DEG C
Stirring is molten clear.Above-mentioned solution is dried with JISL mini spray dryers LSD-48,60 DEG C of inlet temperature, outlet temperature 50 is maintained
DEG C, collect outlet material, obtain white powdery solids, further vacuum drying obtain unformed Yi Palie only with dextrin and poly-
The solid dispersions of ethylene glycol 8000.In the X-ray powder diffraction figure of the solid dispersions, the background peaks of pharmaceutic adjuvant are deducted
Afterwards without the characteristic peak of the net crystal formations of Yi Palie.
Embodiment 4
Yi Palie is net（1 gram）, beta-schardinger dextrin（1 gram）With HPMC E50（0.2 gram）It is added to water（10 milliliters）In,
It is heated to 40 DEG C of stirrings molten clear.By above-mentioned solution freeze-drying, white solid is obtained, i.e., unformed Yi Palie is only and beta-schardinger dextrin
And the solid dispersions of HPMC E50.In the X-ray powder diffraction figure of the solid dispersions, pharmaceutic adjuvant is deducted
Background peaks after the characteristic peak without the net crystal formations of Yi Palie.
Embodiment 5
Yi Palie is net（5 grams）, PVP K30（10 grams）And PEG 8000（50 grams）Melting is heated to, stirring is lower rapid
Room temperature is cooled to, white solid is obtained.By above-mentioned solid crush, obtain white powdery solids, i.e., unformed Yi Palie only with
The solid dispersions of PVP K30 and PEG 8000.In the X-ray powder diffraction figure of the solid dispersions, deduct medicinal
Without the characteristic peak of the net crystal formations of Yi Palie after the background peaks of auxiliary material.
Embodiment 6
Yi Palie is net（1 gram）, ethanol（0.1 gram）, 30 POVIDONE K 30 BP/USP 90（1 gram）And PEG20000（20 grams）It is heated to 240
DEG C, it is well mixed, room temperature is quickly cooled to, obtain white solid.Above-mentioned solid is crushed, white powdery solids is obtained, i.e.,
Unformed Yi Palie only with 30 POVIDONE K 30 BP/USP 90 and the solid dispersions of PEG20000.The X-ray powder of the solid dispersions
In diffraction pattern, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 7
Yi Palie is net（1 gram）, hydroxypropyl cellulose SSL（2 grams）, tetrahydrofuran（10 grams）, ethanol（20 grams）And liposome（4
Gram）Mixture be heated to 60 DEG C, stirring is well mixed, and is evaporated in vacuo and removes solvent, is cooled to room temperature and obtains white powder
Solid, i.e., unformed Yi Palie only with hydroxypropyl cellulose SSL and the solid dispersions of liposome.The X- of the solid dispersions is penetrated
In line powder diagram, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 8
Yi Palie is net（1 gram）, methyl alcohol（20 grams）, polyacrylic resin Eudragit L100（2 grams）And methacrylic acid copolymer
Thing A types（4 grams）Mixture be heated to 50 DEG C, stirring is molten clear, is quickly cooled to -30 DEG C, obtains white powdery solids, i.e.,
Unformed Yi Palie only with polyacrylic resin Eudragit L100 and the solid dispersions of methacrylic acid copolymer A types.Should
In the X-ray powder diffraction figure of solid dispersions, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 9
Yi Palie is net（1 gram）, methyl alcohol（20 grams）, pregelatinized starch（1 gram）And ethyl cellulose（2 grams）Mixture be heated to
30 DEG C, stirring is well mixed, and is evaporated in vacuo and removes solvent, is cooled to room temperature and obtains white powdery solids, i.e., unformed according to handkerchief
Row only with pregelatinated and the solid dispersions of ethyl cellulose.In the X-ray powder diffraction figure of the solid dispersions, medicine is deducted
With the characteristic peak without the net crystal formations of Yi Palie after the background peaks of auxiliary material.
Embodiment 10
Yi Palie is net（1 gram）, methyl alcohol（20 grams）, pregelatinized starch（2 grams）With hydroxypropyl cellulose SSL（4 grams）Mixture
Be heated to 30 DEG C, stir molten clear, be evaporated in vacuo and remove solvent, be cooled to room temperature and obtain white powdery solids, i.e., it is unformed according to
Handkerchief row only with pregelatinized starch and the solid dispersions of hydroxypropyl cellulose SSL.The X-ray powder diffraction of the solid dispersions
In figure, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 11
Yi Palie is net（1 gram）, methyl alcohol（20 grams）, water（10 grams）, microcrystalline cellulose（1 gram）And polyvinyl acetate（4 grams）It is mixed
Compound is heated to 30 DEG C, stirs molten clear, is evaporated in vacuo and removes solvent, is cooled to room temperature and obtains white powdery solids, i.e., without fixed
Type Yi Palie only with microcrystalline cellulose and the solid dispersions of polyvinyl acetate.The X-ray powder diffraction figure of the solid dispersions
In, deduct the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant.
Embodiment 12
Yi Palie is net（50 milligrams）, Macrogol 4000（100 milligrams）With polyacrylic resin Eudragit L100（100 millis
Gram）It is added to methyl alcohol（750 microlitres）, stir molten clear at room temperature, it is evaporated in vacuo and removes solvent, white powdery solids are obtained, i.e.,
Unformed Yi Palie only with Macrogol 4000 and the solid dispersions of polyacrylic resin Eudragit L100.The solid point
The X-ray powder diffraction figure of a prose style free from parallelism as shown in Fig. 2 after the background peaks of pharmaceutic adjuvant are deducted in X-ray powder diffraction figure without according to
Handkerchief arranges the characteristic peak of net crystal formation.
Embodiment 13
Yi Palie is net（50 milligrams）Carboxymethylcellulose calcium phthalic acid ester Agucoat CPD（2 milligrams）With polyacrylic acid tree
Fat Eudragit S100（3 milligrams）It is added to methyl alcohol（4 milliliters）And ethyl acetate（1 milliliter）, stir molten clear at -30 DEG C.Will
Above-mentioned solution concentrates removing solvent thereon in rotary evaporation, is cooled to room temperature, obtains white powdery solids, i.e., unformed according to handkerchief
Row divide with the solid of carboxymethylcellulose calcium phthalic acid ester Agucoat CPD and polyacrylic resin Eudragit S100 only
A prose style free from parallelism.In the X-ray powder diffraction figure of the solid dispersions, without the net crystal formations of Yi Palie after the background peaks of deduction pharmaceutic adjuvant
Characteristic peak.
Embodiment 14
Yi Palie is net（50 milligrams）, dextrin（50 milligrams）With carbopol Carbomer 940（50 milligrams）It is added to methyl alcohol（4
Milliliter）And tetrahydrofuran（1 milliliter）, it is uniformly mixed at -30 DEG C.Above-mentioned solution is concentrated into removing thereon in rotary evaporation
Solvent, is cooled to room temperature, obtains white powdery solids, i.e., unformed Yi Palie only with dextrin and carbopol Carbomer
940 solid dispersions.In the X-ray powder diffraction figure of the solid dispersions, nothing is according to handkerchief after deducting the background peaks of pharmaceutic adjuvant
Arrange the characteristic peak of net crystal formation.
Embodiment 15
Yi Palie is net（50 milligrams）, beta-schardinger dextrin（100 milligrams）With pregelatinized starch Pharma-Gel（100 milligrams）It is added to
Methyl alcohol（4 milliliters）And water（1 milliliter）, it is well mixed at room temperature.By above-mentioned solution, slowly concentration removing is molten in a rotary evaporator
Agent, obtains white powdery solids, i.e., unformed Yi Palie only with beta-schardinger dextrin and the solid of pregelatinized starch Pharma-Gel
Dispersion.In the X-ray powder diffraction figure of the solid dispersions, without the net crystal formations of Yi Palie after the background peaks of deduction pharmaceutic adjuvant
Characteristic peak.
Embodiment 16
Yi Palie is net（50 milligrams）, beta-schardinger dextrin（100 milligrams）With side chain crosslinked starch high（50 milligrams）It is added to methyl alcohol（4
Milliliter）And water（1 milliliter）, stir molten clear at room temperature, by above-mentioned solution, slowly concentration removes solvent in a rotary evaporator, obtains
White powdery solids, i.e., unformed Yi Palie is only and beta-schardinger dextrin（100 milligrams）And the solid dispersion of side chain crosslinked starch high
Body.In the X-ray powder diffraction figure of the solid dispersions, the spy without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted
Levy peak.
Embodiment 17
Yi Palie is net（50 milligrams）, microcrystalline cellulose（100 milligrams）With sodium carboxymethylcellulose SCMC（500 milligrams）It is added to
Dimethyl sulfoxide (DMSO)（5 milliliters）, stir molten clear at room temperature, it is evaporated in vacuo and removes solvent, white powdery solids are obtained, it is further true
Sky is dried, i.e., unformed Yi Palie only with microcrystalline cellulose and the solid dispersions of sodium carboxymethylcellulose SCMC, the solid point
In the X-ray powder diffraction figure of a prose style free from parallelism, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 18
Yi Palie is net（50 milligrams）, Macrogol 4000（100 milligrams）And chitosan（400 milligrams）It is added to ethanol（5 millis
Rise）, stir molten clear at room temperature, by above-mentioned solution, slowly concentration removes solvent in a rotary evaporator, obtains white powder and consolidates
Body, i.e., unformed Yi Palie only with Macrogol 4000 and the solid dispersions of chitosan.The X-ray of the solid dispersions
In powder diagram, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 19
Yi Palie is net（50 milligrams）, microcrystalline cellulose（50 milligrams）With sodium carboxymethyl starch Explotab（500 milligrams）Add
To ethanol（5 milliliters）, it is uniformly mixed at room temperature, by above-mentioned solution, slowly concentration removes solvent in a rotary evaporator, obtains
To white powdery solids, i.e., unformed Yi Palie only with the solid point of D- microcrystalline celluloses and sodium carboxymethyl starch Explotab
A prose style free from parallelism.In the X-ray powder diffraction figure of the solid dispersions, without the net crystal formations of Yi Palie after the background peaks of deduction pharmaceutic adjuvant
Characteristic peak.
Embodiment 20
Yi Palie is net（50 milligrams）, 30 POVIDONE K 30 BP/USP 90（100 milligrams）With alginates E401（100 milligrams）It is added to ethanol（5 millis
Rise）, it is uniformly mixed at room temperature.By above-mentioned solution, slowly concentration removes solvent in a rotary evaporator, obtains white powder
Shape solid, i.e., unformed Yi Palie only with 30 POVIDONE K 30 BP/USP 90 and the solid dispersions of alginates E401.The X- of the solid dispersions is penetrated
In line powder diagram, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 21
Yi Palie is net（50 milligrams）, microcrystalline cellulose（100 milligrams）With carboxymethylcellulose calcium phthalic acid ester Agucoat
CPD（1 gram）It is suspended in methyl alcohol（30 milliliters）, it is heated to 50 DEG C and is uniformly mixed.Above-mentioned solution is delayed in a rotary evaporator
Slow concentration removes most of solvent, and filtering is dried, and obtains white powdery solids, i.e., unformed Yi Palie is only and microcrystalline cellulose
The solid dispersions of element and carboxymethylcellulose calcium phthalic acid ester Agucoat CPD.The X-ray powder of the solid dispersions
In diffraction pattern, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 22
Yi Palie is net（50 milligrams）, natural gum Galactosol（100 milligrams）With carragheen E407（100 milligrams）It is suspended in methyl alcohol
（30 milliliters）, it is heated to 50 DEG C and is uniformly mixed, by above-mentioned solution, slowly concentration removing is most of molten in a rotary evaporator
Agent, filtering, dry, obtain white powdery solids, i.e., unformed Yi Palie only with gummy Galactosol and carragheen E407
Solid dispersions.In the X-ray powder diffraction figure of the solid dispersions, without Yi Palie after the background peaks of deduction pharmaceutic adjuvant
The characteristic peak of net crystal formation.
Embodiment 23
Yi Palie is net（50 milligrams）, microcrystalline cellulose（100 milligrams）And shitosan（200 milligrams）It is suspended in methyl alcohol（50 millis
Rise）, it is heated to 50 DEG C and is uniformly mixed.By above-mentioned solution, slowly concentration removes most of solvent, mistake in a rotary evaporator
Filter, dries, and obtains white powdery solids, i.e., unformed Yi Palie only with microcrystalline cellulose and the solid dispersions of shitosan.
In the X-ray powder diffraction figure of the solid dispersions, the feature without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted
Peak.
Embodiment 24
Yi Palie is net（300 milligrams）, liposome（300 milligrams）With polyacrylic resin Eudragit E100（300 milligrams）
It is dissolved in ethanol（600 microlitres）, tetrahydrofuran（900 microlitres）And N,N-dimethylformamide（600 microlitres）In, it is heated to 50 DEG C and stirs
Mix molten clear, above-mentioned solution is cooled to -30 DEG C, separate out white powdery solids, filtering is dried, and obtains unformed Yi Palie net
With liposome and the solid dispersions of polyacrylic resin Eudragit E100.The X-ray powder diffraction of the solid dispersions
In figure, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 25
Yi Palie is net（30 milligrams）, PEG 8000（30 milligrams）With collagen Peptan（200 milligrams）It is dissolved in ethanol
（600 microlitres）And acetonitrile（600 microlitres）In, it is heated to 50 DEG C of stirrings molten clear.Above-mentioned solution is slow dense in a rotary evaporator
Contracting removes most of solvent, separates out white powdery solids, and filtering is dried, and obtains unformed Yi Palie only and polyethylene glycol
8000 and the solid dispersions of collagen Peptan.In the X-ray powder diffraction figure of the solid dispersions, deduct medicinal auxiliary
Without the characteristic peak of the net crystal formations of Yi Palie after the background peaks of material.
Embodiment 26
Yi Palie is net（30 milligrams）, PEG 8000（30 milligrams）With gummy Galactosol（150 milligrams）It is dissolved in methyl alcohol
（900 microlitres）It is heated to 50 DEG C of stirrings molten clear.By above-mentioned solution, slowly concentration removes solvent in a rotary evaporator, obtains white
Pulverulent solids, that is, obtain unformed Yi Palie only with PEG 8000 and the solid dispersions of natural gum Galactosol.Should
In the X-ray powder diffraction figure of solid dispersions, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 27
Yi Palie is net（30 milligrams）, chitosan（30 milligrams）With hydroxypropyl methylcellulose phthalate HPMCP（30 millis
Gram）It is added to ethanol（750 microlitres）And water（750 microlitres）, it is heated to 80 DEG C and is uniformly mixed.Above-mentioned solution is steamed in rotation
Slow concentration removes solvent in hair device, obtains white powdery solids, i.e., unformed Yi Palie only with chitosan and hydroxypropyl first
The solid dispersions of base cellulose phthalate HPMCP.In the X-ray powder diffraction figure of the solid dispersions, medicine is deducted
With the characteristic peak without the net crystal formations of Yi Palie after the background peaks of auxiliary material.
Embodiment 28
Yi Palie is net（30 milligrams）, microcrystalline cellulose（30 milligrams）And caprolactone（300 milligrams）It is added to ethanol
（750 microlitres）And water（750 microlitres）, it is heated to 80 DEG C and is uniformly mixed.Above-mentioned solution is slow dense in a rotary evaporator
Contracting removes solvent, obtains white powdery solids, i.e., unformed Yi Palie consolidates with microcrystalline cellulose and caprolactone only
Body dispersion.It is only brilliant without Yi Palie after the background peaks of deduction pharmaceutic adjuvant in the X-ray powder diffraction figure of the solid dispersions
The characteristic peak of type.
Embodiment 29
Yi Palie is net（30 milligrams）, beta-schardinger dextrin（60 milligrams）With dextrin Maltrin M100（60 milligrams）It is added to ethanol
（750 microlitres）And water（750 microlitres）, it is heated to 80 DEG C and is uniformly mixed.Above-mentioned solution is slow dense in a rotary evaporator
Contracting removes solvent, obtains white powdery solids, i.e., unformed Yi Palie only with beta-schardinger dextrin and dextrin Maltrin M100
Solid dispersions.It is net without Yi Palie after the background peaks of deduction pharmaceutic adjuvant in the X-ray powder diffraction figure of the solid dispersions
The characteristic peak of crystal formation.
Embodiment 30
Yi Palie is net（30 milligrams）, microcrystalline cellulose（3 milligrams）With sodium carboxymethylcellulose SCMS（3 milligrams）It is added to water
（30 milliliters）, it is heated to 100 DEG C and is uniformly mixed.By above-mentioned solution, slowly concentration removes solvent in a rotary evaporator, obtains
To white powdery solids, i.e., unformed Yi Palie only with butanedioic acid and the solid dispersions of sodium carboxymethylcellulose SCMC.Should
In the X-ray powder diffraction figure of solid dispersions, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 31
Yi Palie is net（5 milligrams）, microcrystalline cellulose（5 milligrams）With PEO Polyox WSR301（30 milligrams）Add
To methyl alcohol（300 microlitres）And water（60 microlitres）, it is uniformly mixed at 60 DEG C.Above-mentioned solution is slow dense in a rotary evaporator
Contracting remove solvent, obtain white powdery solids, i.e., unformed Yi Palie only with microcrystalline cellulose and PEO Polyox
The solid dispersions of WSR301.In the X-ray powder diffraction figure of the solid dispersions, nothing after the background peaks of pharmaceutic adjuvant is deducted
The characteristic peak of the net crystal formations of Yi Palie.
Embodiment 32
Yi Palie is net（30 milligrams）, microcrystalline cellulose（20 milligrams,）PEG 8000（20 milligrams）With polyvinyl alcohol EG-40
（20 milligrams）It is added to methyl alcohol（300 microlitres）And water（60 microlitres）, stir molten clear at 60 DEG C, by above-mentioned solution in rotary evaporator
In slow concentration remove solvent, obtain white powdery solids, i.e., unformed Yi Palie only with microcrystalline cellulose, polyethylene glycol
8000 and the solid dispersions of polyvinyl alcohol EG-40.In the X-ray powder diffraction figure of the solid dispersions, pharmaceutic adjuvant is deducted
Background peaks after the characteristic peak without the net crystal formations of Yi Palie.
Embodiment 33
Yi Palie is net（50 milligrams）, microcrystalline cellulose（50 milligrams）With HPMC acetate succinate Agoat
MG（1 gram）It is added to ethanol（10 milliliters）And water（2 milliliters）, it is uniformly mixed at 80 DEG C, by above-mentioned solution in rotary evaporation
Slow concentration removes solvent in device, obtains white powdery solids, i.e., unformed Yi Palie only with microcrystalline cellulose and hydroxypropyl first
The solid dispersions of base cellulose acetate succinate Agoat MG.In the X-ray powder diffraction figure of the solid dispersions,
Deduct the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant.
Embodiment 34
Yi Palie is net（50 milligrams）, alginates（100 milligrams）And carboxymethylethylcellulose（1 gram）It is added to ethanol（10 millis
Rise）And water（1 milliliter）, it is uniformly mixed at 80 DEG C, by above-mentioned solution, slowly concentration removes solvent in a rotary evaporator, obtains
To white powdery solids, i.e., unformed Yi Palie only with alginates and the solid dispersions of carboxymethylethylcellulose.This is consolidated
In the X-ray powder diffraction figure of body dispersion, the characteristic peak without the net crystal formations of Yi Palie after the background peaks of pharmaceutic adjuvant is deducted.
Embodiment 35：Unformed Yi Palie only with hydroxypropyl cellulose SSL and the influence factor of the solid dispersions of PVP K30
Experiment
Material：The unformed Yi Palie of the gained of embodiment 1 only with hydroxypropyl cellulose SSL and the solid dispersions of PVP K30
Table 1：
Table 1 is illustrated：Unformed Yi Palie is only with hydroxypropyl cellulose SSL and PVP K30 solid dispersions in high temperature, high humidity bar
Under part, place 10 days, relevant material crystallizes precipitation without Yi Palie only without significantly changing.
Embodiment 36：Unformed Yi Palie only with hydroxypropyl cellulose SSL and the accelerated test of PVP K30 solid dispersions
Material：The unformed Yi Palie of the gained of embodiment 1 only with hydroxypropyl cellulose SSL and the solid dispersions of PVP K30
Experiment condition：40 DEG C ± 2 DEG C of temperature, humidity 75% ± 5%
Table 2：
Table 2 is illustrated：Unformed Yi Palie is only with hydroxypropyl cellulose SSL and PVP K30 solid dispersions in accelerated test bar
Under part, place 6 months, relevant material crystallizes precipitation without Yi Palie only without significantly changing.
Yi Palie of the invention only with the unformed solid dispersions of pharmaceutic adjuvant, its dissolution rate substantially increases, is more beneficial for carrying
The bioavilability of medicine high, allows medicament to preferably play clinical disease treatment effect, and the amorphous article is in accelerated test
Under the conditions of（40 ± 2 DEG C, humidity 75% ± 5%）, good physical stability and chemical stability can be kept.
Claims (15)
1. a kind of Yi Palie only with the solid dispersions of pharmaceutic adjuvant, it is characterised in that the solid dispersions include Yi Palie
Only the pharmaceutic adjuvant with two or more, Yi Palie is only 1 with the weight ratio of whole pharmaceutic adjuvants:0.1 ~ 100, wherein,
Yi Palie in the solid dispersions is only unformed shape, in the X-ray powder diffraction spectrum of the solid dispersions, button
Except the characteristic peak without the net crystal of Yi Palie after the background peaks of pharmaceutic adjuvant.
2. Yi Palie according to claim 1 only with the solid dispersions of pharmaceutic adjuvant, it is characterised in that it is described medicinal auxiliary
At least one in material be selected from diluent, lubricant, adhesive, disintegrant, surfactant, filmogen, coating material and
At least one in capsule material.
3. Yi Palie according to claim 1 only with the solid dispersions of pharmaceutic adjuvant, it is characterised in that it is described medicinal auxiliary
At least one in material is selected from HPMC, hydroxypropyl cellulose, PVP, polyethylene glycol, ethyl cellulose, crystallite
Cellulose, liposome, methacrylic acid copolymer, polyvinyl acetate, carboxymethylethylcellulose, carboxymethylcellulose calcium neighbour's benzene two
Formic acid esters, hydroxypropyl methylcellulose phthalate, HPMC acetate succinate, polyacrylic resin,
Carbopol, alginates, carragheen, caprolactone, natural gum, polyvinyl alcohol, pregelatinized starch, crosslinked starch, carboxymethyl
At least one in sodium starch, dextrin, PEO, shitosan, chitosan, collagen and cyclodextrin.
4. a kind of Yi Palie only with the preparation method of the solid dispersions of pharmaceutic adjuvant, comprise the following steps：
Yi Palie is mixed with pharmaceutic adjuvant only, pharmaceutic adjuvant melting is heated to；Wherein, Yi Palie only with whole pharmaceutic adjuvants
Weight ratio is 1:0.1~100；
Cooled down after well mixed, the mixture that will be obtained is crushed, obtain the Yi Palie of unformed shape only with the solid of pharmaceutic adjuvant
Dispersion.
5. Yi Palie according to claim 4 only with the preparation method of the solid dispersions of pharmaceutic adjuvant, it is characterised in that
At least one in the pharmaceutic adjuvant be selected from diluent, lubricant, adhesive, disintegrant, surfactant, filmogen,
At least one in coating material and capsule material.
6. Yi Palie according to claim 4 only with the preparation method of the solid dispersions of pharmaceutic adjuvant, it is characterised in that
At least one in the pharmaceutic adjuvant is selected from HPMC, hydroxypropyl cellulose, PVP, polyethylene glycol, ethyl
Cellulose, microcrystalline cellulose, liposome, methacrylic acid copolymer, polyvinyl acetate, carboxymethylethylcellulose, carboxymethyl
It is cellulose phthalate, hydroxypropyl methylcellulose phthalate, HPMC acetate succinate, poly-
Acrylic resin, carbopol, alginates, carragheen, caprolactone, natural gum, polyvinyl alcohol, pregelatinized starch, crosslinking
In starch, sodium carboxymethyl starch, dextrin, PEO, shitosan, chitosan, collagen and cyclodextrin at least one
Kind.
7. a kind of Yi Palie only with the preparation method of the solid dispersions of pharmaceutic adjuvant, comprise the following steps：
Yi Palie is net and pharmaceutic adjuvant mixes in a solvent, mixing temperature is -50 ~ 150 DEG C, formed containing Yi Palie it is net with it is medicinal
The solution or suspension of auxiliary material, wherein, Yi Palie is only 0.001 ~ 100 with the weight ratio of solvent:1, Yi Palie only with whole medicines
It is 1 with the weight ratio of auxiliary material:0.1~100；
Removing step 1）Solvent in the solution or suspension that obtain, obtains the Yi Palie of unformed shape and consolidates with pharmaceutic adjuvant only
Body dispersion.
8. Yi Palie according to claim 7 only with the preparation method of the solid dispersions of pharmaceutic adjuvant, it is characterised in that
At least one in the pharmaceutic adjuvant be selected from diluent, lubricant, adhesive, disintegrant, surfactant, filmogen,
At least one in coating material and capsule material.
9. Yi Palie according to claim 7 only with the preparation method of the solid dispersions of pharmaceutic adjuvant, it is characterised in that
At least one in the pharmaceutic adjuvant is selected from HPMC, hydroxypropyl cellulose, PVP, polyethylene glycol, ethyl
Cellulose, liposome, microcrystalline cellulose, methacrylic acid copolymer, polyvinyl acetate, carboxymethylethylcellulose, carboxymethyl
It is cellulose phthalate, hydroxypropyl methylcellulose phthalate, HPMC acetate succinate, poly-
Acrylic resin, carbopol, alginates, carragheen, caprolactone, natural gum, polyvinyl alcohol, pregelatinized starch, crosslinking
In starch, sodium carboxymethyl starch, dextrin, PEO, shitosan, chitosan, collagen and cyclodextrin at least one
Kind.
10. Yi Palie according to claim 7 only with the preparation method of the solid dispersions of pharmaceutic adjuvant, its feature exists
In step 1）The solvent be selected from the alcohols containing less than 12 carbon atoms, phenols, ethers, halogenated hydrocarbons, ketone, aldehydes, nitrile,
At least one in acid amides, sulfone, sulfoxide, carboxylic acid and water；Step 2）The method for removing solvent includes：Evaporation, vacuum evaporation, spraying
Drying, freeze-drying, hot-melt extruded, filtering, centrifugation or agitated thin film.
11. a kind of Pharmaceutical compositions, it is characterised in that the Pharmaceutical composition contains unformed Yi Palie only and two kinds or two kinds
More than pharmaceutically acceptable auxiliary material, at least one in the pharmaceutic adjuvant is selected from diluent, lubricant, adhesive, collapses
At least one in solution agent, surfactant, filmogen, coating material and capsule material.
12. Pharmaceutical compositions according to claim 11, it is characterised in that in the pharmaceutic adjuvant in the Pharmaceutical composition
At least one be selected from HPMC, hydroxypropyl cellulose, PVP, polyethylene glycol, ethyl cellulose, microcrystalline cellulose
Element, liposome, methacrylic acid copolymer, polyvinyl acetate, carboxymethylethylcellulose, carboxymethylcellulose calcium phthalic acid
Ester, hydroxypropyl methylcellulose phthalate, HPMC acetate succinate, polyacrylic resin, poly- carboxylic
Ethene, alginates, carragheen, caprolactone, natural gum, polyvinyl alcohol, pregelatinized starch, crosslinked starch, CMS
At least one in sodium, dextrin, PEO, shitosan, chitosan, collagen and cyclodextrin.
13. a kind of Pharmaceutical compositions, it is characterised in that said composition contains the net solid dispersions of unformed Yi Palie and at least one
Plant pharmaceutically acceptable auxiliary material.
14. compositions according to claim 13, it is characterised in that the solid dispersions in said composition are comprising unformed according to handkerchief
Arrange net and at least two pharmaceutically acceptable auxiliary materials.
15. claim 13-14 it is any as described in composition be used to prepare the purposes of antidiabetic medicine.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3556355A1 (en) * | 2018-04-18 | 2019-10-23 | Zentiva, K.S. | Particles containing amorphous empagliflozin, process for their preparation and pharmaceutical preparation |
| CN111214450A (en) * | 2020-04-23 | 2020-06-02 | 上海翰森生物医药科技有限公司 | Empagliflozin tablet and preparation process thereof |
| WO2021123165A1 (en) | 2019-12-19 | 2021-06-24 | Krka, D.D., Novo Mesto | Dosage form comprising amorphous solid solution of empagliflozin with polymer |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014161919A1 (en) * | 2013-04-05 | 2014-10-09 | Boehringer Ingelheim International Gmbh | Therapeutic uses of empagliflozin |
-
2015
- 2015-12-10 CN CN201510910666.5A patent/CN106880595A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014161919A1 (en) * | 2013-04-05 | 2014-10-09 | Boehringer Ingelheim International Gmbh | Therapeutic uses of empagliflozin |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3556355A1 (en) * | 2018-04-18 | 2019-10-23 | Zentiva, K.S. | Particles containing amorphous empagliflozin, process for their preparation and pharmaceutical preparation |
| WO2021123165A1 (en) | 2019-12-19 | 2021-06-24 | Krka, D.D., Novo Mesto | Dosage form comprising amorphous solid solution of empagliflozin with polymer |
| CN111214450A (en) * | 2020-04-23 | 2020-06-02 | 上海翰森生物医药科技有限公司 | Empagliflozin tablet and preparation process thereof |
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Application publication date: 20170623 |