CN1853726A - Polymer system for improving insoluble medicine water solubility and preparation thereof - Google Patents
Polymer system for improving insoluble medicine water solubility and preparation thereof Download PDFInfo
- Publication number
- CN1853726A CN1853726A CNA2005100647065A CN200510064706A CN1853726A CN 1853726 A CN1853726 A CN 1853726A CN A2005100647065 A CNA2005100647065 A CN A2005100647065A CN 200510064706 A CN200510064706 A CN 200510064706A CN 1853726 A CN1853726 A CN 1853726A
- Authority
- CN
- China
- Prior art keywords
- neo
- houttuyninum
- injection
- sodium
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
A sodium neohouttuyfonate injection in the form of liquid injection, aseptic powder injection, freeze-dried powder injection, glucose injection, sodium chloride injection, or glucose-sodium chloride injection features that it contains the water-soluble high-polymer system consisting of polyvidone, polyethanediol or hydroxypropyl methylcellulose and 2-hydroxypropyl-beta- cyclodextrin in order to improve its water solubility.
Description
Technical field:
What the present invention relates to is the preparation method of neo-houttuyninum sodium injection, is specifically to contain a kind of in polyvidone, Polyethylene Glycol or the hydroxypropyl emthylcellulose or and the ternary of several and 2-hydroxypropyl, neo-houttuyninum preparation or polynary clathrate injection and preparation method thereof.
Background technology:
(β-CD) can carry out clathration with chemical compound lot helps changing the multiple physicochemical properties of guest molecule to beta-schardinger dextrin-usually behind the enclose, as dissolubility in the raising water and stability etc.But because the enclose small amount of drug often need use a large amount of CD, enclose efficient is not high, and therefore in the forming process of medicine beta-CD inclusion, the normal different additive of service condition waits as surfactant, organic solvent and to improve enclose efficient.Discover, different additives is to the remarkable influence that is formed with of clathrate, hydrophobic antiseptic molecule can cement out drug molecule from the CD hole, little hydrophobic molecule such as ethanol and propyleneglycoles all have the trend that reduces enclose, yet hydroxypropyl emthylcellulose but can strengthen dexamethasone and the 2-hydroxypropyl (clathration of HP-β-CD).High polymer is an important research of carrying out in the recent period to the influence of 2-hydroxypropyl clathration, does not domesticly see bibliographical information as yet.
Neo-houttuyninum (New Houttuynium) chemical name is a lauroyl acetyl sodium sulfite, it is the sodium sulfite addition product of lauroyl acetyl, for China's initiative is used for clinical effective antibiosis anti-inflammatory drug, clinical pelvic inflammatory disease, the adnexitis of being used for the treatment of has curative effect preferably.In addition, the effect that neo-houttuyninum (I) is grown in the mice body to the mice ehrlich ascites cell and to cancerous cell in the influence of C-AMP level, the result shows: behind the I of different time by mouse peritoneal injection various dose, the ascites volume of tumor animal, cancerous cell sum and cancerous cell division branch secretary all have obvious reduction, and the C-AMP level has and increases in the cancerous cell, especially with administration group (34mg/kg) These parameters there is tangible influence, the experimental result prompting, I may be relevant with C-AMP level in the raising cancerous cell to the inhibition effect of ehrlich carcinoma.
Synthetic neo-houttuyninum is white flakey or needle-like or crystalline powder, easily molten in hot water, slightly soluble in water, ethanol, its raw material and injection are ministry standard, and standard No. is respectively: WS-10001-(HD-0484)-2002 and WS-10001-(HD-0391)-2002.Because raw material slightly soluble in water, in order to make injection, essentially in prescription add in a large number as solubilizing agents such as tween 80s, and tween 80 is a non-ionic surface active agent, not only produces haemolysis, and certain toxicity is arranged.In addition, pain appears in this injection when intramuscular injection, and the patient produces pain psychology in use; Easily separate out crystallization simultaneously in storage period, in order to solve neo-houttuyninum vein dissolubility and intramuscular injection pain problem, the patent that someone has applied for " novel decanoy acetaldelzy sodium intravenous and preparation method thereof ", number of patent application is 021350302, publication number is CN1404825.The applicant still uses tween 80 as solubilizing agent, and consumption is very big, contains tween 80 7～30g in every 1000ml injection.Promptly 0.7%～3% concentration is once imported the about 1g tween 80 of human body, and human body is had certain toxicity.The somebody has applied for " application of 2-hydroxypropyl in the preparation of neo-houttuyninum sodium injection ", and number of patent application is 03112411; And " injection neo-houttuyninum sodium freeze-dried powder injection and preparation method thereof ", number of patent application is 03126536.These two pieces of patents are all used cyclodextrin, neo-houttuyninum is made cyclodextrin clathrate, reach the purpose of solubilising, patent 03126536 has also been carried out hemolytic test, toxicity test, hypersensitive test, the test of intravenous injection blood vessel irritation to prepared injection, and result of the test shows that it possesses haemolysis not, does not produce acute poisoning symptom, non-sensitization, does not cause the characteristics of blood vessel irritation.2-hydroxypropyl (or cyclodextrin and other derivants) large usage quantities that two pieces of patents are used, with the ratio of neo-houttuyninum be 5～500: 1, the 2-hydroxypropyl costs an arm and a leg, cost is higher; And the 2-hydroxypropyl clathrate of neo-houttuyninum easily produces precipitation when adding the dilution of chlorination sodium injection, so just limited use clinically.
Summary of the invention:
The objective of the invention is deficiency, injection of the ternary clathrate that water soluble polymer and 2-hydroxypropyl and neo-houttuyninum form and preparation method thereof is provided at the patented technology of existing neo-houttuyninum sodium injection.Hydroxypropyl is the derivant of beta-schardinger dextrin-, and its water solublity is high, under the room temperature, can reach (beta-schardinger dextrin-only is 2%) more than 50%, and nontoxic, nonirritant, be a good used for intravenous injection adjuvant.The present invention has added water soluble polymers such as polyvidone again in the neo-houttuyninum clathrate system with the hydroxypropyl preparation, further improved solubilizing effect, and can make the injection system more stable.
In polyvidone or Polyethylene Glycol and the application of hydroxypropyl series derivates in the preparation of neo-houttuyninum sodium injection, the weight ratio scope of neo-houttuyninum and polyvidone or Polyethylene Glycol and cyclodextrin derivative is 1: (0.25～5): (1～15).
Above-mentioned polyvidone specification comprises: K12PF, K17PF, K29～32PF etc.
Above-mentioned Polyethylene Glycol specification comprises: PEG400, PEG600, PEG1000, PEG1500, PEG4000.
The optimum specifications of polyvidone is K12PF in the application of this preparation; The optimum specifications of Polyethylene Glycol is PEG400; The cellulosic optimum specifications of hydroxypropyl ylmethyl is 5～10mPa.s.
The optimum range of the weight ratio of neo-houttuyninum and 30 POVIDONE K 30 BP/USP 12PF is 1: 0.25～5 in the application of this preparation; The optimum range that neo-houttuyninum is received with the weight ratio of 2-hydroxypropyl is 1: 10～15.
Described neo-houttuyninum sodium injection comprises: new houttuynine sodium bisulfite injection, neo-houttuyninum sodium freeze-drying powder, neo-houttuyninum aseptic powder injection, neo-houttuyninum glucose injection, injection liquid containing sodium decanoy acetaldehyde and sodium chloride.
For water soluble polymers such as explanation polyvidone and Polyethylene Glycol play the effect of assisting solubilising to the neo-houttuyninum cyclodextrin clathrate, carried out following test.
Test 1: the determining of clathrate dissolubility type
Draw the solubility curve figure (Fig. 1) of neo-houttuyninum.From Fig. 1 as seen, the apparent solubility of neo-houttuyninum is linear increasing along with the increase of 2-HP-concentration, meets the A of the phase solubility curve of Higuchi establishment
LType illustrates the formation of soluble agents-cyclodextrin clathrate, and behind the adding polyvidone, the solubility curve of clathrate still belongs to solubility A
LType, i.e. the adding of high polymer does not influence the type of solubility curve, but the dissolubility increase of neo-houttuyninum is more very, has the formation of thermodynamically stable three molecular clathrates, remains further to be studied.
Test 2: the selection of high polymer optium concentration
PEG and PVP are at 0～5.0g.L as seen from Figure 2
-1During scope, along with the increase of superpolymer concentration, the dissolubility of neo-houttuyninum increases, but when surpassing this concentration, may may the amplitude that the neo-houttuyninum dissolubility increases be decreased because viscosity increases.So select 1.0～10.0g.L for use
-1Concentration range be suitable.As seen from Figure 2, the optium concentration zone of high polymer is 3.0～5.0g.L in 2-hydroxypropyl aqueous solution
-1Between.
Test 3: high polymer is to the solubilizing effect of clathrate
In inclusion complex in solution, add 5g.L respectively
-1PVP-K12PF and PEG-400, in the following vibration 30min of 20,25,30,37 ℃ constant temperatures, behind filtering with microporous membrane, get in right amount, add the 0.01mol/L sodium hydroxide solution, measure trap at 283nm, measure reference substance solution with method, obtain concentration, the results are shown in Table 1.
Test 4: high polymer is to the thermodynamic study of clathration mechanism
In clathrate, add variable concentrations (2.0～5.0g.L respectively
-1) PVP-K12PF and PEG-400, will add PVP-K12PF and PEG-400 sample earlier and reach balance in the vibration of 20,25,30,37 ℃ constant temperature, behind filtering with microporous membrane, it is an amount of to get filtrate, the sodium hydroxide solution that adds 0.01mol/L is diluted to scale.Measuring absorption value in the 283nm place, obtain concentration with the measurement result of reference substance solution, is vertical coordinate with the superpolymer concentration, and clathrate concentration is abscissa, gets the linear equation that variable concentrations adds PVP-K12PF down.According to following equation and list of references, press Kc=slope/intercept (1-slope) and calculate conditional formation constant.Obtain linear equation and the conditional formation constant of PEG-400 again with above-mentioned experimental technique, the results are shown in Table 2.
Table 1 adding PVP-k12PF and PEG400 are to the influence of neo-houttuyninum dissolubility
| T/℃ | C(mol.L -1) | Dissolubility (C 2/C 1) | |||
| 20 25 30 37 | In the water 0.03625 0.06823 0.07122 0.07319 | Among the PVP-K12PF 0.1012 0.1498 0.1456 0.1450 | Among the PEG-400 0.08981 0.1132 0.1201 0.1198 | Add PVP-K12PF 2.79 2.20 2.04 1.98 | Add PEG-400 2.48 1.66 1.69 1.64 |
Table 2 PVP-K12PF and PEG-400 are to the influence of thermodynamic function
| T/℃ | Conditional formation constant (Kc) | Gibbs function (Δ G °)/KJ.mol -1 | ||||
| 20 25 37 | Clathrate 6,285 6,266 4532 | Add PVP-K12PF 11,965 12,011 11659 | Add PEG-400 10,012 9,998 7896 | Clathrate-21.30-21.66-21.70 | Add PVP-K12PF-22.87-23.27-24.13 | Add PEG-400-22.44-22.82-23.12 |
By result in the table as seen, in clathrate, behind the adding high polymer, the conditional formation constant of clathration is increased, enclose efficient increases, the free enthalpy of clathration descends simultaneously, proves that the existence of high polymer increases the spontaneous trend of clathration, and inclusion reaction is easier to carry out.
Investigate from the chemical thermodynamics aspect, add water soluble polymer and can make clathration trend become big, integral energy reduces, and system is in more stable status, wherein has the formation of chemically stable three molecule inclusion systems.
Description of drawings:
The solubility curve figure of Fig. 1 neo-houttuyninum
Among the figure: series 1 is neo-houttuyninum and 2-HP-binary system; Series 2 is the ternary system that neo-houttuyninum, 2-HP-and polyvidone are formed; Series 3 is the ternary system that neo-houttuyninum, 2-HP-and Polyethylene Glycol are formed.Wherein the concentration of high polymer is 5g.L
-1
Fig. 2 superpolymer concentration is to the influence of neo-houttuyninum dissolubility
Series 1: add the influence of PEG400 to HP-β-CD solution relative viscosity;
Series 2: add the influence of PVP-K12PF to HP-β-CD solution relative viscosity
The specific embodiment:
Embodiment 1: take by weighing 30 POVIDONE K 30 BP/USP 12PF0.5g, 2-hydroxypropyl 10g, place the 100ml distilled water, stirring and dissolving.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and dissolving gets solution.Add lactose 4g in the solution, stirring and dissolving, gained solution is behind vacuum drying, or spray drying or lyophilization, gets white powder, i.e. neo-houttuyninum-polyvidone-hydroxypropyl ternary clathrate.This clathrate adds water, and dissolubility is good again, i.e. dissolving fully in 5 seconds.
Embodiment 2: take by weighing 30 POVIDONE K 30 BP/USP 17PF 0.4g, 2-hydroxypropyl 10g, place the 100ml distilled water, stirring and dissolving.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and heating for dissolving gets solution.Add mannitol 4g in the solution, after the lyophilization of gained solution, get white block.After being dissolved in water, dissolubility is good again.
Embodiment 3: take by weighing 30 POVIDONE K 30 BP/USP 29～320.3g, 2-hydroxypropyl 10g, place the 100ml distilled water, stirring and dissolving.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add dextran 4g, gained solution gets white block through lyophilization, and water dissolubility again is good, can be used for disposing other dosage forms.
Embodiment 4: take by weighing 30 POVIDONE K 30 BP/USP 12PF 0.5g, 2-hydroxypropyl 8g, place the 100ml distilled water, be heated to 60～90 ℃, i.e. dissolving in 10 minutes.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add xylitol 4g, pack into the cillin bottle of 5ml of gained solution branch, through lyophilization, white block, the gained block is loose, water dissolubility again is good, can be used for disposing other dosage forms.
Embodiment 5: take by weighing 30 POVIDONE K 30 BP/USP 12PF 0.5g, 2-hydroxypropyl 12.5g, place the 100ml distilled water, stirring at room i.e. dissolving in 15 minutes.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add active carbon 0.5g, stirred 15 minutes, filter carbon removal, add water for injection to 250ml, gained solution is sub-packed in the ampoule of 2ml, 5ml, 10ml, gets new houttuynine sodium bisulfite injection (specification is respectively 2ml:4mg, 5ml:10mg, 10ml:20mg).
Embodiment 6: take by weighing 30 POVIDONE K 30 BP/USP 12PF 0.5g, 2-hydroxypropyl 15g, place the 100ml distilled water, stirring at room i.e. dissolving in 15 minutes.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add active carbon 0.5g, stirred 15 minutes, filter carbon removal, add water for injection to 250ml, gained solution is sub-packed in the ampoule of 2ml, 5ml, 10ml, gets new houttuynine sodium bisulfite injection (specification is respectively 2ml:4mg, 5ml:10mg, 10ml:20mg).Also can add mannitol 4g, divide in the cillin bottle of packing into, the packing volume is respectively 0.4ml, 1ml, 2ml.Lyophilization gets white block.
Embodiment 7: take by weighing PEG400 0.5g, 2-HP-10.0g, place the 100ml distilled water, stirring at room i.e. dissolving in 15 minutes.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add active carbon 0.5g, stirred 15 minutes, filter carbon removal, add water for injection to 250ml, gained solution is sub-packed in the ampoule of 2ml, 5ml, 10ml, gets new houttuynine sodium bisulfite injection (specification is respectively 2ml:4mg, 5ml:10mg, 10ml:20mg).
Embodiment 8: take by weighing PEG600 0.4g, 2-HP-10.0g, place the 100ml distilled water, stirring at room i.e. dissolving in 15 minutes.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add active carbon 0.5g, stirred 15 minutes, filter carbon removal, add water for injection to 250ml, gained solution is sub-packed in the ampoule of 2ml, 5ml, 10ml, gets new houttuynine sodium bisulfite injection (specification is respectively 2ml:4mg, 5ml:10mg, 10ml:20mg).
Embodiment 9: take by weighing PEG1000 0.3g, 2-HP-10.0g, place the 100ml distilled water, stirring at room i.e. dissolving in 15 minutes.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add active carbon 0.5g, stirred 15 minutes, filter carbon removal, add water for injection to 250ml, gained solution is sub-packed in the ampoule of 2ml, 5ml, 10ml, gets new houttuynine sodium bisulfite injection (specification is respectively 2ml:4mg, 5ml:10mg, 10ml:20mg).
Embodiment 10: take by weighing PEG1500 0.3g, 2-HP-10.0g, place the 100ml distilled water, stirring at room i.e. dissolving in 15 minutes.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add active carbon 0.5g, stirred 15 minutes, filter carbon removal, add water for injection to 250ml, gained solution is sub-packed in the ampoule of 2ml, 5ml, 10ml, gets new houttuynine sodium bisulfite injection (specification is respectively 2ml:4mg, 5ml:10mg, 10ml:20mg).
Embodiment 11: take by weighing PEG4000 0.3g, 2-HP-12.5g, place the 100ml distilled water, stirring at room i.e. dissolving in 15 minutes.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add active carbon 0.5g, stirred 15 minutes, filter carbon removal, add water for injection to 250ml, gained solution is sub-packed in the ampoule of 2ml, 5ml, 10ml, gets new houttuynine sodium bisulfite injection (specification is respectively 2ml:4mg, 5ml:10mg, 10ml:20mg).
Embodiment 12: (specification: 55mPa.s) 0.3g, 2-HP-12.5g place the 100ml distilled water, stirring at room i.e. dissolving in 15 minutes to take by weighing HPMC.Other gets neo-houttuyninum 1g, adds in the above-mentioned solution, and ultrasonic hydrotropy gets solution.Add active carbon 0.5g, stirred 15 minutes, filter carbon removal, add water for injection to 250ml, gained solution is sub-packed in the ampoule of 2ml, 5ml, 10ml, gets new houttuynine sodium bisulfite injection (specification is respectively 2ml:4mg, 5ml:10mg, 10ml:20mg).
Claims (8)
1. the application of water soluble polymer in the neo-houttuyninum sodium injection, be added with 2-HP-cyclodextrin in injection, the weight ratio scope of neo-houttuyninum, water soluble polymer and 2-HP-is 1: 0.2～10: 2.5～50.
2. application as claimed in claim 1, wherein water soluble polymer is preferably polyvidone, Polyethylene Glycol or hydroxypropyl emthylcellulose.
3. application as claimed in claim 2, wherein water soluble polymer polyvidone more preferably.
4. application as claimed in claim 3, wherein polyvidone polyvidone-K12PF more preferably.
5. application as claimed in claim 4, wherein the usage ratio of neo-houttuyninum, polyvidone-K12PF and 2-HP-is with 1: 1～2: 10～15 optimums.
6. the application of water soluble polymer according to claim 1 in the preparation of neo-houttuyninum sodium injection, be characterised in that: the neo-houttuyninum sodium injection comprises: new houttuynine sodium bisulfite injection, neo-houttuyninum sodium freeze-drying powder, neo-houttuyninum aseptic powder injection and neo-houttuyninum glucose injection.
7. the application of water soluble polymer according to claim 6 in the preparation of neo-houttuyninum sodium injection, it is characterized in that: the neo-houttuyninum sodium freeze-drying powder is at the neo-houttuyninum sodium solution or after adding mannitol, lactose, dextran or xylose alcohols excipient therein, gets through lyophilization.
8. according to the application of the described water soluble polymer of claim 6 in neo-houttuyninum sodium injection preparation, it is characterized in that: the neo-houttuyninum glucose injection is to make solvent with 5～10% glucose solutions, through 115 ℃ of pressure sterilizings after 20 minutes and get.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2005100647065A CN1853726A (en) | 2005-04-18 | 2005-04-18 | Polymer system for improving insoluble medicine water solubility and preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2005100647065A CN1853726A (en) | 2005-04-18 | 2005-04-18 | Polymer system for improving insoluble medicine water solubility and preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1853726A true CN1853726A (en) | 2006-11-01 |
Family
ID=37194376
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005100647065A Pending CN1853726A (en) | 2005-04-18 | 2005-04-18 | Polymer system for improving insoluble medicine water solubility and preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1853726A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100594940C (en) * | 2007-08-08 | 2010-03-24 | 昆明制药集团股份有限公司 | Supermolecule water soluble freeze drying matter of indissoluble medicament and method of preparing the same |
| CN101524554B (en) * | 2009-04-08 | 2012-08-01 | 上海卫康光学眼镜有限公司 | Composition used with contact lens for cleaning and disinfection and application thereof |
| CN110279657A (en) * | 2019-07-29 | 2019-09-27 | 河南官渡生物工程有限公司 | A kind of sodium closantel injection and preparation method thereof |
-
2005
- 2005-04-18 CN CNA2005100647065A patent/CN1853726A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100594940C (en) * | 2007-08-08 | 2010-03-24 | 昆明制药集团股份有限公司 | Supermolecule water soluble freeze drying matter of indissoluble medicament and method of preparing the same |
| CN101524554B (en) * | 2009-04-08 | 2012-08-01 | 上海卫康光学眼镜有限公司 | Composition used with contact lens for cleaning and disinfection and application thereof |
| CN110279657A (en) * | 2019-07-29 | 2019-09-27 | 河南官渡生物工程有限公司 | A kind of sodium closantel injection and preparation method thereof |
| CN110279657B (en) * | 2019-07-29 | 2021-07-27 | 河南官渡生物工程有限公司 | Closantel sodium injection and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5369332B2 (en) | Pharmaceutical composition containing docetaxel having stability, and method for producing the same | |
| JP5380549B2 (en) | Voriconazole-containing drug formulation and preparation method thereof | |
| AU2019219792B2 (en) | Bendamustine anionic-cationic cyclopolysaccharide compositions | |
| US9993561B2 (en) | Rifaximin complexes | |
| AU2013334921B2 (en) | Alkylated cyclodextrin compositions and processes for preparing and using the same | |
| CA2753641A1 (en) | Bendamustine cyclopolysaccharide compositions | |
| EA009714B1 (en) | Cladribine formulations for improved oral and transmucosal delivery | |
| AU2004226437B2 (en) | Oral formulations of cladribine | |
| CN1853726A (en) | Polymer system for improving insoluble medicine water solubility and preparation thereof | |
| RU2322979C2 (en) | Temosolomide-containing system for controlled release | |
| CN104606151A (en) | PG (prostaglandin) E1 cyclodextrin inclusion compound lyophilized preparation and preparation method thereof | |
| JP6654703B2 (en) | Drug inclusion compound, preparation thereof, and production method therefor | |
| Lima et al. | Evaluation of in vitro dissolution of benznidazole and binary mixtures: Solid dispersions with hydroxypropylmethylcellulose and β-cyclodextrin inclusion complexes | |
| JP6654702B2 (en) | Oral formulation and production method thereof | |
| WO2007142440A1 (en) | Stable pharmaceutical composition containing paclitaxel and a method of manufacturing the same | |
| OCHIUZ et al. | Development study of new topical formulations with erythromycin | |
| Higashi et al. | Synthesis of cyclodextrin-based polyrotaxanes and polycatenanes for supramolecular pharmaceutical sciences | |
| CA2575916A1 (en) | Methods and compositions to reduce tissue irritation in parenteral formulations | |
| HORTOLOMEI et al. | Development study of new topical formulaঞons with erythromycin | |
| CN103622906A (en) | High drug-loading capacity amphotericin B polymer composite micelle and preparation method thereof | |
| WO2006034849A1 (en) | Antitumoral pharmaceutical compositions comprising a spisulosine and a cyclodextrin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |