CN107496397A - A kind of compound and its preparation of melbine and Fenofibric Acid - Google Patents
A kind of compound and its preparation of melbine and Fenofibric Acid Download PDFInfo
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- CN107496397A CN107496397A CN201610426941.0A CN201610426941A CN107496397A CN 107496397 A CN107496397 A CN 107496397A CN 201610426941 A CN201610426941 A CN 201610426941A CN 107496397 A CN107496397 A CN 107496397A
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- melbine
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- fenofibric acid
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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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
- A61K9/20—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
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
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- Pharmacology & Pharmacy (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of melbine and the compound and its preparation of Fenofibric Acid, the compound is obtained by melbine and the direct salt-forming reaction of Fenofibric Acid.Because experiment is proved using compound of the present invention as the enteric-coated sustained-release preparation prepared by active component, melbine and Fenofibric Acid two kinds of active components can be released in simulated intestinal fluid is simulated, and there is extraordinary release consistency between the two；Therefore, compound of the present invention can be used for the pharmaceutical preparation for preparing the treatment metabolic disease such as high fat of blood and diabetes.The pharmacokinetics that the present invention is not only solved between two kinds of active components discharges problem of inconsistency caused by not being consistent; and there is obvious slow release; without food effect and in advance release conditions; meet the Clinical practice requirement of pharmaceutical preparation; and good with compressibility, preparation technology is simple, is easy to scale; cost is low, the advantages that steady quality.
Description
Technical field
The present invention is to be related to a kind of compound and its preparation of melbine and Fenofibric Acid, belongs to pharmaceutical technology field.
Background technology
Melbine is a kind of biguanides, it is known that it mainly has antihypertensive active, and is widely used in treatment non-insulin and relies on
Property diabetes, melbine can also be applied to patient with insulins combinations；Known melbine is soluble in water and difficult compacting
Material, the difficult compacting material refer to not bond the material to form tablet when applying press power.
Fenofibrate, be a kind of lipid regulating agent, available for reduce blood in triglycerides (fat-like material) level,
Specifically, fenofibrate can reduce high LDL-C, total-C, triglycerides and Apo-B and HDL-C is increased, the medicine
Also it has been approved as complementary therapy to be used to treat hypertriglyceridemia, the illness is characterized in the extra-low density in blood plasma
The horizontal rise of lipoprotein (VLDL), it is known that the compound is hydrophobic, is insoluble in water, bioavilability than relatively low, and
Food effect (absorption increase of the fenofibrate in alimentary canal after patient consuming food) be present.
Research report at present：Melbine and fenofibrate can therapeutic alliance diabetes or hyperlipemia, there is Synergistic to make
With；Such as：Pruski M et al. result of study shows that melbine is with fenofibrate therapeutic alliance with dyslipidemia
Type II diabetes, effect are better than single drug, have synergy；Nieuwdorp M et al. result of study shows, two
First biguanides and fenofibrate therapeutic alliance metabolic syndrome, effect is better than single drug, without extra side effect；Victor
Hugo Oidor-Chan et al. research is thought, in the rat model of type II diabetes and acute myocardial infarction AMI, low dosage
Melbine and fenofibrate therapeutic alliance, show cardioprotection, it is possible to provide a kind of prevention type II diabetes
The method of the heart ischemia reperfusion damage of patient；Krysiak R et al. result of study shows that melbine can strengthen leaching
Bar Carbazole alkaloid, fenofibrate have protection of ecs and whole body antiinflammatory action, and impaired glucose tolerance patients can benefit from fenofibrate
With the melbine therapeutic alliance of high dose.
Because melbine is hydrophilic component, and fenofibrate is hydrophobic components, two kinds of activearms in single composition
Point bioavilability can be hindered, the presence of hydrophobicity fenofibrate can delay the dissolving of melbine so as to influence two
The bioavilability of first biguanides, so that release and absorption between the two in vivo does not have uniformity, so as to have impact on combination
The pharmacokinetic property of thing preparation, turn into the difficult problems of exploitation said composition preparation.In order to overcome melbine and non-promise
Bei Te releases in vivo and absorb and do not have the problem of uniformity, Chinese patent ZL200580002928.2 is disclosed containing two
The composition of first biguanides particle and shellfish spy's particle, the wherein average grain diameter of melbine particle are 125 μm~250 μm, Bei Te
Mean particle size is less than 10 μm, and shellfish spy's particle is attached on melbine particle, and " Bei Te " needs are micro-
Efflorescence, " Bei Te " is preferably fenofibrate, although the patent declare to solve both melbine and fenofibrate it
Between existing physico-chemical property significant difference caused by pharmacokinetic property it is inconsistent the problem of (do not provided in the patent
The release profiles of the composition formed), but the average grain diameter of patent requirements shellfish spy's particle is less than 10 μm, and require " shellfish
Spy " particle is attached on melbine particle, and not only the preparation technology to preparation and equipment propose very high request, are unfavorable for
Industrialized production, and the quality of the pharmaceutical preparations is difficult to stabilization.
Fenofibric Acid, chemical name are 2- [4- (4- chlorobenzene formacyls) phenoxy group] -2- rnethyl-propanoic acids, are the active generations of fenofibrate
Thank to product, T-CHOL, LDL-C, apolipoprotein B, total triglycerides and richness in treated patient can be made
Lipoprotein (VLDL) containing triglycerides declines.Known Fenofibric Acid has higher solubility in small intestine area, bioavilability compared with
Height, still, the enhancing of solubility can cause relevant issues：CmaxBeyond acceptable (accreditation) scope, such as：
The immediate release dosage form for including amorphous Fenofibric Acid is described in U.S. Patent application 2005/0148594, as the patent is reported
Lead：When being applied to patient, the preparation comprising amorphous Fenofibric Acid shows the institute of embodiment 6 equivalent to the published application
The bioavilability for twice of the capsule comprising fenofibrate stated.Accordingly, it is considered to the difference to above-mentioned solubility, it is impossible to non-
Promise shellfish acid simply replaces the fenofibrate in the formulation.
Further, since the melbine active component clinically used at present derives from Metformin, Fenofibric Acid is lived
Property ingredient origin, if making both salt directly be applied in combination, can have following defect in Fenofibric Acid choline salt：
1) cause the dosage of prescription substantially to increase, be unfavorable for clinically taking；
2) poor compressibility, friability is higher, sliver easily occurs during tabletting, obtained label is of low quality, directly affects
Coating quality, so as to cause, preparation qualification rate is not high, Antacid effectiveness is unqualified；
3) it is crucial that both pharmacokinetic property is not still consistent, release in vivo with absorb still do not possess it is consistent
Property, there are problems that discharging in advance, be unfavorable for industrialized production and clinical practice, hinder the association of melbine and Fenofibric Acid
With the performance of synergistic effect, it is unfavorable for formulation development, the exploitation of the sustained release preparation especially with pharmacokinetics uniformity.
The content of the invention
In view of the above-mentioned problems existing in the prior art, it is an object of the invention to provide one kind can solve melbine and Fenofibric Acid
Pharmacokinetics the problem of not being consistent and melbine and the compound and its preparation of Fenofibric Acid with release consistency,
With meet melbine and Fenofibric Acid clinically requirement is applied in combination.
For achieving the above object, the technical solution adopted by the present invention is as follows：
A kind of compound of melbine and Fenofibric Acid, obtained by melbine and the direct salt-forming reaction of Fenofibric Acid.
Preferably, the compound is to be with Fenofibric Acid according to mol ratio in suitable solvent by melbine
3:1~1:3 (be preferably 1.5:1~1:1) obtained in 20~80 DEG C of (being preferably 40~60 DEG C) reactions.
The suitable solvent includes but is not limited to methanol, ethanol, isopropanol, ethylene glycol, hexylene glycol, isobutanol, isoamyl
Alcohol, acetone, espeleton, methylisobutylketone, dichloromethane, chloroform, tetrahydrofuran, benzene,toluene,xylene,
Ether, expoxy propane, methyl acetate, ethyl acetate, propyl acetate, acetonitrile, pyridine, phenol, glycol monoethyl ether,
Ethylene glycol ethyl ether, butyl glycol ether, isopropyl ether, petroleum ether, ethylene glycol monobutyl ether, hexamethylene, n-hexane, cyclohexanone,
The organic solvents such as toluene cyclohexanone, or the mixed solvent formed by several organic solvents, or had by described at least one
The mixed solvent that solvent is formed with water.
Preferably, the suitable solvent include but is not limited to methanol, ethanol, isopropanol, ethylene glycol, hexylene glycol,
The organic solvents such as isobutanol, isoamyl alcohol, or by several mixed solvents formed in them, or by least one of they
The mixed solvent formed with water.
A kind of pharmaceutical preparation of melbine and Fenofibric Acid, it is characterised in that：The active component of the pharmaceutical preparation is this hair
The compound of bright described melbine and Fenofibric Acid.
Preferably, melbine and Fenofibric Acid of the present invention containing 30~90wt% in the pharmaceutical preparation
Compound.
Preferably, described pharmaceutical preparation is sustained release preparation, including described melbine and Fenofibric Acid is compound
Thing and slow-release material, the slow-release material may be selected from HPMC, hydroxypropyl cellulose, methylcellulose, ethyl
Cellulose, carbomer, sodium carboxymethylcellulose, polyoxyethylene, polyethylene glycol, xanthans, alginate, polyethylene pyrrole
It is pyrrolidone, starch, the cross-linked homopolymer of acrylic acid or copolymer, Utech S100, Utech NE, Utech NM, outstanding
Special strange RS30D, Utech RS PO, Utech FS30D, Utech L100, Utech L30D-55, gelatin, Brazil
In palm sodium, cocoa butter, stearyl alcohol, beeswax, insect wax, microwax, Arabic gum, carrageenan, silicon rubber extremely
Few one kind.
As further preferred scheme, the described melbine and Fenofibric Acid containing 50~85wt% in the sustained release preparation
Compound.
As further preferred scheme, folic acid and vitamin B12 are also contained in described sustained release preparation.
As further preferred scheme, described sustained release preparation is oral solid formulation, including but not limited to tablet, capsule,
Granule and pill.
As still more preferably scheme, described sustained release preparation is enteric-coated sustained-release preparation, in addition to enteric coating, the enteric
Clothing may be selected from methacrylic acid copolymer, methacrylate copolymer, ethyl acrylate/methacrylic acid copolymer, adjacent benzene
Dioctyl phthalate cellulose acetate, Hydroxypropyl Methylcellulose Phathalate, d ritalinic acid cellulose, butanedioic acid hydroxypropylmethylcellulose acetate first
Base cellulose, poly- phthalic acid vinylacetate, trimellitic acid cellulose acetate, carboxymethylethylcellulose, shellac
At least one of.
As still more preferably scheme, the enteric coating is made up of Utech L30D-55, talcum powder and triethyl citrate.
As still more preferably scheme, the enteric coating is by 10.4 mass parts Utech L30D-55,5.2 mass parts talcum powder
Formed with 1.6 mass parts triethyl citrates.
As still more preferably scheme, described sustained release preparation also includes pharmaceutically acceptable excipient, the excipient
Including appointing in filler, adhesive, lubricant, solubilizer, glidant, supensoid agent, pigment, anticaking agent, solvent
Meaning is one or more.
As still more preferably scheme, the core of the sustained release preparation has following compositing formula in terms of 100 mass parts：
As still more preferably scheme, the slow-release material selects HPMC or Utech NE30D；It is described to fill out
Fill agent and select microcrystalline cellulose or HPMC；Described adhesive selects PVP；The glidant selects colloid two
Silica；The lubricant selects magnesium stearate.
As still more preferably scheme, the preparation of the enteric-coated sustained-release preparation is first to use wet method or dry granulation (with wet method
Granulation is preferable), then tabletting, then it is enteric coated.
As still more preferably scheme, the preparation of the enteric-coated sustained-release preparation is first to use centrifugal granulating, extrusion spheronization or liquid
Phase lamination method prepares pastille micropill (preferable with centrifugal granulating and extrusion spheronization), then enteric coated then encapsulated.
As still more preferably scheme, the preparation of the enteric-coated sustained-release preparation is first to use wet method or dry granulation (with wet method
Granulation is preferable), then tabletting, enteric coated then encapsulated.
Compared with prior art, the present invention has following conspicuousness beneficial effect：
1) experiment proves：Using the compound of melbine of the present invention and Fenofibric Acid as the enteric prepared by active component
Sustained release preparation, melbine and Fenofibric Acid two kinds of active components can be released in simulated intestinal fluid is simulated, and had between the two
There is extraordinary release consistency；Therefore, although not combining in currently available technology on melbine with Fenofibric Acid also
Diabetes or the document report of high fat of blood are treated, but because Fenofibric Acid is the active metabolite of fenofibrate, in vivo
The actually active composition to work is Fenofibric Acid, and the compound of the present invention can be released to diformazan in simulated intestinal fluid is simulated
Biguanides and Fenofibric Acid two kinds of active components, it can thus be assumed that compound of the present invention is for treatment diabetes or high blood
Fat, particularly there is pharmacological action and curative effect with the type II diabetes of dyslipidemia, high fat of blood and sugar are treated available for preparing
Urinate the pharmaceutical preparation of the metabolic diseases such as disease.
2) present invention is not only efficiently solved by creatively making melbine directly form compound into salt with Fenofibric Acid
Pharmacokinetics between the two discharges problem of inconsistency caused by not being consistent, and has obvious slow release, can keep away
Exempt from food effect present in single-activity composition and in advance release conditions, meet the Clinical practice requirement of pharmaceutical preparation；
3) it can avoid two kinds of active components respectively into the compressibility present in recombinant use after salt is bad, easy sliver and friability are asked
Topic, not only preparation technology is simply easy to scale, and preparation qualification rate is high, and cost is low, steady quality, is especially suitable for work
Industry metaplasia is produced, and has application value.
Brief description of the drawings
Fig. 1 is the In-vitro release curves of preparation 1 that the embodiment of the present invention 2 is provided in simulated intestinal fluid is simulated；
Fig. 2 is the In-vitro release curves of preparation 2 that the embodiment of the present invention 2 is provided in simulated intestinal fluid is simulated；
Fig. 3 is the In-vitro release curves of preparation 3 that the embodiment of the present invention 2 is provided in simulated intestinal fluid is simulated；
Fig. 4 is the In-vitro release curves of preparation 4 that the embodiment of the present invention 2 is provided in simulated intestinal fluid is simulated；
Fig. 5 is the In-vitro release curves of preparation 5 that the embodiment of the present invention 2 is provided in simulated intestinal fluid is simulated；
Fig. 6 is the In-vitro release curves of control sample that comparative example of the present invention is provided in simulated intestinal fluid is simulated.
Embodiment
Technical solution of the present invention is described in further detail and completely with reference to embodiment and comparative example.
Embodiment 1：The preparation of the compound of melbine and Fenofibric Acid
Embodiment 1.1
Taking 12.9g melbine and 31.9g Fenofibric Acids, (both mol ratios are 1:1) it is placed in 500mL three-neck flask,
250mL isopropanols are added, are heated to 80 DEG C, insulation reaction 2h；Being concentrated under reduced pressure makes reaction solution volume be decreased to about 100mL,
Cooling, standing make crystallization, crystal are collected by filtration, and dry, produce the compound of melbine and Fenofibric Acid of the present invention
Thing 36.2g (white crystalline solid).
Embodiment 1.2
Taking 19.4g melbine and 31.9g Fenofibric Acids, (both mol ratios are 1.5:1) it is placed in 500mL three-neck flask,
300mL 95wt% ethanol is added, is heated to 60 DEG C, insulation reaction 2h；Being concentrated under reduced pressure makes reaction solution volume be decreased to about
150mL, cooling, standing make crystallization, crystal are collected by filtration, and dry, produce melbine of the present invention and fenofibrate
The compound 37.9g (white crystalline solid) of acid.
Embodiment 2：The preparation of enteric-coated sustained-release preparation
Embodiment 2.1：The preparation of preparation 1
1) prescription of preparation 1 is as follows：
2) preparation technology is as follows：
Testing result on release conditions in the friability of prepared preparation 1, sliver situation, acid is shown in Table 1.
Embodiment 2.2：The preparation of preparation 2
1) prescription of preparation 2 is as follows：
2) preparation technology is as follows：
Testing result on release conditions in the friability of prepared preparation 2, sliver situation, acid is shown in Table 1.
Embodiment 2.3：The preparation of preparation 3
1) prescription of preparation 3 is as follows：
2) preparation technology is as follows：
Testing result on release conditions in the friability of prepared preparation 3, sliver situation, acid is shown in Table 1.
Embodiment 2.4：The preparation of preparation 4
1) prescription of preparation 4 is as follows：
2) preparation technology is as follows：
Testing result on burst size in the friability of prepared preparation 4, sliver situation, acid is shown in Table 1.
Embodiment 2.5：The preparation of preparation 5
1) prescription of preparation 5 is as follows：
2) preparation technology is as follows：
Testing result on release conditions in the friability of prepared preparation 5, sliver situation, acid is shown in Table 1.
Comparative example
1) prescription of Comparative formulation is as follows：
2) preparation technology is as follows：
The testing result of release conditions is shown in Table 1 in friability, sliver situation, acid on prepared Comparative formulation.
Burst size test data in the friability of 1 each preparation of table, sliver situation, acid
| Preparation | Friability/% | Sliver situation | Burst size/% in acid |
| Preparation 1 | 0.08 | Nothing | 0 |
| Preparation 2 | 0.11 | Nothing | 0 |
| Preparation 3 | 0.15 | Nothing | 0 |
| Preparation 4 | 0.21 | Nothing | 0 |
| Preparation 5 | 0.14 | Nothing | 0 |
| Comparative formulation | 1.5 | Have | More than 10% |
From the result of table 1：The compound of melbine and Fenofibric Acid provided by the invention has extraordinary briquettability,
Under equal conditions, relative to directly using Metformin hydrochloride and Fenofibric Acid choline salt as active component preparation of preparation when, pressure
The occurred friability of system substantially reduces, and does not occur sliver situation, finished product acid-resisting is strong, and the burst size in acid is zero, is said
Bright is not in food effect and release conditions in advance.
Release is tested
Dissolution test is carried out to the preparation 1-5 and Comparative formulation of above-mentioned preparation using dual pH methods, actual conditions is as follows：
The release profiles of each preparation are visible with reference to Fig. 1-6 respectively as shown in Fig. 1-6：With melbine of the present invention with it is non-
Enteric-coated sustained-release preparation of the compound of promise shellfish acid prepared by active component, melbine can be released in simulated intestinal fluid is simulated
With Fenofibric Acid two kinds of active components, and there is extraordinary release consistency between the two, high fat of blood is treated available for preparing
With the pharmaceutical preparation of the metabolic disease such as diabetes；In addition, under equal conditions, with melbine of the present invention with it is non-
Sustained release preparation prepared by the compound of promise shellfish acid, relative to directly using Metformin hydrochloride and Fenofibric Acid choline salt as activity
For sustained release preparation prepared by composition, slow release is more preferable, more meets the clinical practice requirement of sustained release preparation.
Finally need it is pointed out here that be：It the above is only the part preferred embodiment of the present invention, it is impossible to be interpreted as protecting the present invention
Protect the limitation of scope, some nonessential modifications and adaptations that those skilled in the art makes according to the above of the present invention
Belong to protection scope of the present invention.
Claims (10)
- A kind of 1. compound of melbine and Fenofibric Acid, it is characterised in that：The compound is by melbine and non-promise The directly salt-forming reaction of shellfish acid obtains.
- 2. the compound of melbine according to claim 1 and Fenofibric Acid, it is characterised in that：The compound is In suitable solvent it is 3 according to mol ratio by melbine and Fenofibric Acid:1~1:3 obtain in 20~80 DEG C of reactions.
- 3. the compound of melbine according to claim 2 and Fenofibric Acid, it is characterised in that：It is described suitable molten Agent includes but is not limited to methanol, ethanol, isopropanol, ethylene glycol, hexylene glycol, isobutanol, isoamyl alcohol, acetone, methyl fourth Ketone, methylisobutylketone, dichloromethane, chloroform, tetrahydrofuran, benzene,toluene,xylene, ether, expoxy propane, Methyl acetate, ethyl acetate, propyl acetate, acetonitrile, pyridine, phenol, glycol monoethyl ether, ethylene glycol ethyl ether, second two Appointing in alcohol butyl ether, isopropyl ether, petroleum ether, ethylene glycol monobutyl ether, hexamethylene, n-hexane, cyclohexanone, toluene cyclohexanone Meaning is a kind of, or by several formed mixed solvents therein, or by least one mixed solvent formed with water therein.
- A kind of 4. pharmaceutical preparation of melbine and Fenofibric Acid, it is characterised in that：The active component of the pharmaceutical preparation is power Profit requires the compound of the melbine and Fenofibric Acid in 1-3 described in any one.
- 5. the pharmaceutical preparation of melbine according to claim 4 and Fenofibric Acid, it is characterised in that：The medicine system The compound of melbine containing 30~90wt% and Fenofibric Acid in agent.
- 6. the pharmaceutical preparation of the melbine and Fenofibric Acid according to claim 4 or 5, it is characterised in that：The medicine Thing preparation is sustained release preparation, including the compound and slow-release material of described melbine and Fenofibric Acid.
- 7. the pharmaceutical preparation of melbine according to claim 6 and Fenofibric Acid, it is characterised in that the sustained release system The core of agent has following compositing formula in terms of 100 mass parts：
- 8. the pharmaceutical preparation of melbine according to claim 7 and Fenofibric Acid, it is characterised in that：The sustained release material Material selects HPMC or Utech NE30D；The filler selects microcrystalline cellulose or HPMC； Described adhesive selects PVP；The glidant selects cataloid；The lubricant selects magnesium stearate.
- 9. the pharmaceutical preparation of melbine according to claim 6 and Fenofibric Acid, it is characterised in that：The sustained release system Also contain folic acid and vitamin B12 in agent.
- 10. the pharmaceutical preparation of melbine according to claim 6 and Fenofibric Acid, it is characterised in that：The sustained release Preparation is enteric-coated sustained-release preparation, in addition to enteric coating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610426941.0A CN107496397A (en) | 2016-06-14 | 2016-06-14 | A kind of compound and its preparation of melbine and Fenofibric Acid |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610426941.0A CN107496397A (en) | 2016-06-14 | 2016-06-14 | A kind of compound and its preparation of melbine and Fenofibric Acid |
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| CN107496397A true CN107496397A (en) | 2017-12-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610426941.0A Pending CN107496397A (en) | 2016-06-14 | 2016-06-14 | A kind of compound and its preparation of melbine and Fenofibric Acid |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10577379B1 (en) | 2018-12-05 | 2020-03-03 | Jiangxi Fushine Pharmaceutical Co., Ltd. | Fenofibric acid salt with berberine or its analogues, crystalline forms, methods of preparation, and applications thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1424070A1 (en) * | 2002-11-28 | 2004-06-02 | Fournier Laboratories Ireland Limited | Combination of a PPAR alpha agonist and metformin for decreasing the serum triglycerides |
| WO2006135480A2 (en) * | 2005-04-08 | 2006-12-21 | Abbott Laboratories | Oral pharmaceutical formulations comprising fenofibric acid and/or its salts |
| CN101677981A (en) * | 2006-10-12 | 2010-03-24 | 艾博特实验室 | Pharmaceutical formulations |
| KR20140131859A (en) * | 2013-05-06 | 2014-11-14 | 한미약품 주식회사 | Composite formulation comprising a film coating layer containing rosuvastatin or a pharmaceutically acceptable salt thereof |
-
2016
- 2016-06-14 CN CN201610426941.0A patent/CN107496397A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1424070A1 (en) * | 2002-11-28 | 2004-06-02 | Fournier Laboratories Ireland Limited | Combination of a PPAR alpha agonist and metformin for decreasing the serum triglycerides |
| WO2006135480A2 (en) * | 2005-04-08 | 2006-12-21 | Abbott Laboratories | Oral pharmaceutical formulations comprising fenofibric acid and/or its salts |
| CN101677981A (en) * | 2006-10-12 | 2010-03-24 | 艾博特实验室 | Pharmaceutical formulations |
| KR20140131859A (en) * | 2013-05-06 | 2014-11-14 | 한미약품 주식회사 | Composite formulation comprising a film coating layer containing rosuvastatin or a pharmaceutically acceptable salt thereof |
Non-Patent Citations (1)
| Title |
|---|
| 李秀云等: "《药物不良反应观察》", 31 March 2012 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10577379B1 (en) | 2018-12-05 | 2020-03-03 | Jiangxi Fushine Pharmaceutical Co., Ltd. | Fenofibric acid salt with berberine or its analogues, crystalline forms, methods of preparation, and applications thereof |
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Application publication date: 20171222 |