CN101273980A - Preparation of Enrofloxacin microcapsule and method of preparing the same - Google Patents
Preparation of Enrofloxacin microcapsule and method of preparing the same Download PDFInfo
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- CN101273980A CN101273980A CNA2008100918516A CN200810091851A CN101273980A CN 101273980 A CN101273980 A CN 101273980A CN A2008100918516 A CNA2008100918516 A CN A2008100918516A CN 200810091851 A CN200810091851 A CN 200810091851A CN 101273980 A CN101273980 A CN 101273980A
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The invention discloses an enrofloxacin microcapsule preparation and a preparation method thereof. The enrofloxacin microcapsule preparation is prepared by 5 percent to 90 percent of enrofloxacin raw material and 95 to 10 percent of accessories, and the accessory is one of the followings or a mixture mixed by a plurality of the followings: 12 to 18 carbon fatty acid, calcium stearate monoglycerol ester, stearyl alcohol, saturated triglyceride, glycerol monoester, paraffin, animal wax, vegetable wax and fat powder, etc.. The appearance of the enrofloxacin microcapsule preparation is a white or light yellow spherical granule, the dispersion performance is good, the used accessory is safe, and the enrofloxacin microcapsule preparation has no toxicity or side effects for livestock and poultry and has a gradual release in stomach and intestine, thus maintaining the durability of the efficacy.
Description
Technical field
The invention belongs to field of medicaments, relate to preparation of Enrofloxacin microcapsule and preparation method thereof specifically.
Background technology
Enrofloxacin is a kind of antimicrobial drug of synthetic animal specific, belongs to third generation quinolones preparation.Enrofloxacin has broad-spectrum bactericidal action, antibacterial to resting stage and trophophase is all effective, it is to multiple gram positive bacteria and gram negative bacteria, and mycoplasma has good killing action, and is effective as bacillus pyocyaneus, escherichia coli, Salmonella, shigella, klebsiella, pasteurella, Bacillus proteus, staphylococcus, chlamydia etc.
Because enrofloxacin is to act on bacterial cell DNA helicase, can make antibacterial can not form superhelix, chromosome is impaired, thereby produces bactericidal action.Different with other drug because of its sterilization mechanism, so it is very little to produce the chance of cross resistance, and the toxicity of enrofloxacin is minimum, uses therapeutic dose not have teratogenesis, mutagenic action, and is clinical safe in utilization.
In actual production, enrofloxacin is subjected to numerous raisers' trust owing to its good result of use.At present, common enrofloxacin dosage form mainly contains on the market: tablet, soluble powder, solution, injection or the like.Wherein, the injection dosage form belongs to individual administration, and its shortcoming is to be not suitable for intensifying the use of large-scale farming; Other dosage forms all are oral, are fit to individual administration, still, because enrofloxacin is very bitter, and scent of, when oral, can influence palatability on the one hand, can stimulation be arranged to the stomach of poultry on the other hand, cause vomiting in the time of serious, even some pig taste of smelling enrofloxacin feedstuff of just be unwilling to taking food.
Therefore, how to eliminate the bitterness and the abnormal smells from the patient of enrofloxacin, and the novel form research that does not influence the therapeutic effect of enrofloxacin causes people's attention, present domestic correlational study mainly contains following several:
The first, change molecular structure by chemical reaction.For example Enrofloxacin HCL, enrofloxacin sodium, lactic acid enrofloxacin etc., but this method can cause the rising of pharmacy cost, and to the improvement effect of medicine and not obvious.
The second, make the dosage form of bag quilt, microcapsule or taste masking.The patent No. is husky star microcapsule of a kind of coating agent type promise and preparation method for the ZL200510050039.5 Chinese patent discloses, and mainly is at outer twice parcel of coating materials of using of enrofloxacin granule, can add sweeting agent more in addition, so covers the bitterness of enrofloxacin.This method production process dust is bigger, except that workman's production environment is relatively poor, by the analysis to product on the market, finds that most of parcel that exists is incomplete, the shortcoming that coating rate is low.Application number is the preparation method that the Chinese patent application of 200610049243.X discloses a kind of taste masking type enrofloxacin, it is mixed to be about to gelatin and glycerol, make gelatin-plasticizer composite solution, again the enrofloxacin input is made suspension, afterwards with the suspension spray drying, this procedure is very complicated, operation inconvenience.
Summary of the invention
One of technical issues that need to address of the present invention provide a kind of novel preparation of Enrofloxacin microcapsule, and this microcapsule formulation is effectively eliminated the bitterness and the abnormal smells from the patient of enrofloxacin, and do not influence the result of use of enrofloxacin.
A kind of preparation of Enrofloxacin microcapsule, be that the enrofloxacin raw material of 5%-60% and adjuvant that content is 40-95% are prepared from by content mainly, described adjuvant is one or more mixing in 12 to 18 carbon fatty acids, single-stearic acid glyceride, hard ester alcohol, saturated triglyceride, monoglyceride, paraffin, animal wax, vegetable wax, the fatty powder etc.
Preferably, the content of enrofloxacin raw material is 10%-50%, and correspondingly, the content of adjuvant is 50-90%, the content 10% or 50% of enrofloxacin raw material more preferably, and the content of adjuvant is 90% or 50%.
Preferably, described adjuvant is a stearic acid, fatty powder, one or more in single-stearic acid glyceride and the paraffin.
Another technical issues that need to address of the present invention provide the method for the above-mentioned 'Ennoxacin ' micro-capsule system of preparation.
A kind of method for preparing above-mentioned 'Ennoxacin ' micro-capsule system mainly may further comprise the steps:
(1) with the adjuvant heating, melt, and stir, described adjuvant is one or more mixing in 12 to 18 carbon fatty acids, single-stearic acid glyceride, hard ester alcohol, saturated triglyceride, monoglyceride, paraffin, animal wax, vegetable wax, the fatty powder etc.;
(2) with the enrofloxacin raw material with melt after adjuvant mix, wherein, the enrofloxacin material content is 5%-60%, adjuvant content is 40-95%, shear agitation 5-60 minute, temperature was controlled to be 65～120 ℃;
(3) with stirred materials insulation heating in the step (two), temperature is 65 ℃-120 ℃;
(4) spray granulation;
(5) cooling, concussion is sieved, and collects.
Preferably, the temperature of adjuvant heating and melting is 55 ℃-120 ℃, more preferably 65～90 ℃; Insulation heating-up temperature in the step (three) is 65 ℃-100 ℃.
The preparation method of preparation of Enrofloxacin microcapsule of the present invention is simple, cost is low, easy to operate, loss is few, total yield of products height, the preparation of Enrofloxacin microcapsule outward appearance that its production the obtains faint yellow or yellow spheroidal particle that is white in color, microscopically is viewed as translucent, size 200 μ m-850 μ m, good fluidity more helps mixing with food.By preparation method provided by the invention, in conjunction with selected adjuvant, the preparation of Enrofloxacin microcapsule that obtains is compared with plain particles has significant improvement, and mainly contain: used adjuvant is simple, does not add sweeting agent in addition, and safety has no side effect to poultry; Cover the bitterness of enrofloxacin fully, be that easily poultry accept, changed the present situation that the enrofloxacin oral solid formulation is difficult to be applied to pig, enlarged its scope of application; Good stability can slowly discharge in gastrointestinal, keeps the persistency of drug effect, and it is longer that effective blood peak concentration of drug is held time, and it is more lasting to act on.
Description of drawings
Fig. 1 is 'Ennoxacin ' micro-capsule preparation flow figure of the present invention
Fig. 2 is a sketch map under the 'Ennoxacin ' micro-capsule microscope of the present invention (40 times).
1. adjuvant;
2. enrofloxacin raw material;
3. change batch can;
4. material-compound tank;
5. storage tank;
6. sprayer unit;
7. cooling system;
8. vibrosieve.
The specific embodiment
Embodiment one
Select adjuvant 1 stearic acid (meet " quality standard of stearic acid (Stearic Acid) in Chinese pharmacopoeia or " American Pharmacopeia ", " European Pharmacopoeia ", " British Pharmacopoeia ") 225kg inputization batch can 3 for use, as shown in Figure 1, be heated to 80 ℃, constantly stir, treat that adjuvant 1 all melts; To melt hard ester acid and pump into material-compound tank 4 from change batch can, the 25kg enrofloxacin raw material 2 of accurately weighing simultaneously drops into material-compound tank 4, emulsify at a high speed shear agitation 10 minutes, and temperature will be controlled at 80 ℃ therebetween; The material that prepared is imported storage tank 5, and heating-up temperature to 80 ℃-100 ℃; Start defeated material sprayer unit 6, this sprayer unit 6 can be Highspeedcentrifugingandsprayingdrier, and proportioned material in the storage tank 5 is granulated by spray cooling (cooling system 7); With made finished particle with 200um-850um concussion sieve 8 collection of sieving.Obtain 303kg finished product preparation of Enrofloxacin microcapsule (10% content) at last, particle diameter is at 200 μ m-700 μ m, and yield can reach 97%.As shown in Figure 2, preparation of Enrofloxacin microcapsule is translucent under 40 power microscopes, faint yellow spheroidal particle.
Embodiment two
Select adjuvant single-stearic acid glyceride 120kg inputization batch can for use, be heated to 70 ℃, constantly stir, treat that adjuvant all melts; To melt calcium stearate list glyceride and pump into material-compound tank from change batch can, accurately the enrofloxacin 80kg of weighing drops into material-compound tank simultaneously, shear agitation 8 minutes, and temperature will remain on 80 ℃ therebetween; The material that prepared is imported storage tank, and heating-up temperature to 80 ℃-100 ℃; Start defeated material sprayer unit, proportioned material in the storage tank is granulated by spray chilling equipment; Made finished particle is sieved the collection of sieving with 200 μ m-850 μ m concussion.Obtain 190kg finished product preparation of Enrofloxacin microcapsule (40%) at last, particle diameter is at 200 μ m-850 μ m, and yield can reach 95%.
Embodiment three
Select single-stearic acid glyceride 60kg, fatty powder 60kg, paraffin 20kg inputization batch can for use, be heated to 90 ℃, constantly stir, treat that adjuvant all melts; The adjuvant that has melted is pumped into material-compound tank from change batch can, accurately the enrofloxacin 60kg of weighing drops into material-compound tank simultaneously, shear agitation 8 minutes, and temperature will remain on 80 ℃ therebetween; The material that prepared is imported storage tank, and heating-up temperature to 80 ℃-100 ℃; Start defeated material sprayer unit, proportioned material in the storage tank is granulated by spray chilling; Made finished particle is sieved the collection of sieving with 200 μ m-850 μ m concussion.Obtain 190kg finished product preparation of Enrofloxacin microcapsule (30%) at last, particle diameter is at 200 μ m-850 μ m, and yield can reach 95%.
Embodiment four
Select adjuvant 1 fatty powder 100kg inputization batch can 3 for use, be heated to 80 ℃, constantly stir, treat that adjuvant 1 all melts; To melt fatty powder and pump into material-compound tank 4 from change batch can, the 100kg enrofloxacin raw material 2 of accurately weighing simultaneously drops into material-compound tank 4, and emulsify at a high speed shear agitation 10 minutes will make temperature remain on 80 ℃ therebetween; The material that prepared is imported storage tank 5, and heating-up temperature to 80 ℃-100 ℃; Start defeated material sprayer unit 6, this sprayer unit 6 can be high speed centrifugation spray cooling machine, and proportioned material in the storage tank 5 is granulated by spray cooling; With made finished particle with 200um-850um concussion sieve 8 collection of sieving.Obtain 194kg finished product preparation of Enrofloxacin microcapsule (50% content) at last, particle diameter is at 200 μ m-850 μ m, and yield can reach 97%.Preparation of Enrofloxacin microcapsule is translucent under 40 power microscopes, yellow spheroidal particle.
Experimental example five:
Give the pig feeding that needs treatment with the 'Ennoxacin ' micro-capsule for preparing among the embodiment four.Experimental results show that through 'Ennoxacin ' micro-capsule agent pharmacokinetics:
The former powder of preparation of Enrofloxacin microcapsule and enrofloxacin sees Table 1 and table 2 respectively in the intravital determination of plasma concentration value of pig.Two preparations see Table 3 and table 4 in the intravital pharmacokinetic parameters of pig.
Table 1 preparation of Enrofloxacin microcapsule is at the intravital determination of plasma concentration value of pig (X ± SD, μ g/ml)
| 24 | 0.832 | 0.503 | 0.665 | 1.187 | 1.585 | 0.679 | 1.051 | 0.760 | 1.005 | 1.080 | 0.93 | 0.31 |
| 36 | 0.449 | 0.153 | 0.237 | 0.525 | 0.893 | 0.408 | 0.530 | 0.354 | 0.395 | 0.400 | 0.43 | 0.20 |
| 48 | 0.388 | 0.126 | 0.071 | 0.278 | 0.472 | 0.255 | 0.405 | 0.196 | 0.248 | 0.416 | 0.29 | 0.13 |
| 72 | 0.211 | 0.036 | ND | 0.076 | 0.166 | 0.102 | 0.184 | 0.063 | 0.083 | 0.194 | 0.11 | 0.07 |
| 96 | 0.115 | ND | ND | 0.021 | 0.058 | 0.041 | 0.084 | 0.020 | 0.027 | 0.091 | 0.05 | 0.04 |
Annotate: ND represents not detect, and is lower than detectability 0.02 μ g/ml
The former powder of table 2 enrofloxacin is at the intravital determination of plasma concentration value of pig (X ± SD, μ g/ml)
Table 3 preparation of Enrofloxacin microcapsule is at the intravital pharmacokinetic parameters of pig (X ± SD)
| Tp | h | 3.59 | 4.51 | 6.82 | 6.72 | 8.93 | 4.87 | 5.86 | 5.04 | 5.93 | 3.84 | 5.61 | 1.51 |
| C max | ug/ml | 1.20 | 1.20 | 1.79 | 2.58 | 2.60 | 1.33 | 1.61 | 1.48 | 1.74 | 1.70 | 1.72 | 0.48 |
| AUC | mg/l. | 51.69 | 29.17 | 39.03 | 68.63 | 87.89 | 41.86 | 59.59 | 39.81 | 48.92 | 60.07 | 52.67 | 15.64 |
| lagtime | h | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.38 | 0.22 | 0.06 | 0.14 |
The former powder of table 4 enrofloxacin is at the intravital pharmacokinetic parameters of pig (X ± SD)
Show by above data:
1, the peak concentration that reaches of preparation of Enrofloxacin microcapsule and former powder is respectively 1.72h and 2.53h.Compare with former powder, microcapsule formulation of the present invention is lower in the intravital concentration of pig, but it is longer to hold time.The blood drug level of microcapsule formulation group and former powder group is respectively 0.11 μ g/ml and 0.04 μ g/ml during 72h after administration, and the microcapsule formulation group is 0.05 μ g/ml during 96h after administration, and the blood drug level of former powder group fails to measure.
2, do contrast with the former powder of enrofloxacin, preparation of Enrofloxacin microcapsule administration post-absorption for oral administration is complete, and its relative bioavailability is up to 115.8%.
The preparation of Enrofloxacin microcapsule that above embodiment 1-3 prepares has above-mentioned same effect, and detailed data is omitted.
Above-listed detailed description is at the specifying of possible embodiments of the present invention, and is not in order to limiting claim of the present invention, does not allly break away from the equivalence that skill spirit of the present invention does and implements or change, all should be contained in the claim of this case.
Claims (8)
1. preparation of Enrofloxacin microcapsule, it is characterized in that, by content is that the enrofloxacin raw material of 5-60% and adjuvant that content is 40-95% are prepared from, and described adjuvant is one or more in 12 to 18 carbon fatty acids, single-stearic acid glyceride, hard ester alcohol, saturated triglyceride, monoglyceride, paraffin, animal wax, vegetable wax, the fatty powder.
2. preparation of Enrofloxacin microcapsule according to claim 1 is characterized in that, the content of described enrofloxacin raw material is 10%-50%, and the content of described adjuvant is 50-90%.
3. preparation of Enrofloxacin microcapsule according to claim 1 is characterized in that, the content of described enrofloxacin raw material is 10% or 50%, and the content of described adjuvant is 90% or 50%.
4. according to the described preparation of Enrofloxacin microcapsule of claim 1, it is characterized in that the particle diameter of described preparation of Enrofloxacin microcapsule is 200 μ m-850 μ m, the outward appearance faint yellow or yellow spheroidal particle that is white in color.
5. according to the described preparation of Enrofloxacin microcapsule of claim 1, it is characterized in that described adjuvant is a stearic acid, fatty powder, one or more in single-stearic acid glyceride and the paraffin.
6. a method for preparing claim 1 or 2 described 'Ennoxacin ' micro-capsule systems is characterized in that, mainly may further comprise the steps:
(1) with the adjuvant heating, melts, and stir;
(2) with the enrofloxacin raw material with melt after adjuvant mix, shear agitation 5-60 minute, temperature was controlled at 65～100 ℃;
(3) with stirred materials insulation heating in the step (two), temperature is 65 ℃-100 ℃;
(4) material spray is granulated;
(5) cooling, concussion is sieved, and collects promptly.
7. preparation method according to claim 6 is characterized in that, the temperature of adjuvant heating and melting is 55 ℃-120 ℃ in the step ().
8. preparation method according to claim 6 is characterized in that, the insulation heating-up temperature in the step (three) is 80 ℃-100 ℃.
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| CN2008100918516A CN101273980B (en) | 2007-06-08 | 2008-03-31 | Preparation of Enrofloxacin microcapsule and method of preparing the same |
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| CN200710028484.0 | 2007-06-08 | ||
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101965913A (en) * | 2010-10-20 | 2011-02-09 | 无锡正大畜禽有限公司 | Production method for tasteless enteric enrofloxacin microcapsules |
| CN103239422A (en) * | 2012-04-26 | 2013-08-14 | 浙江康德权科技有限公司 | Preparation method of smellless coated enrofloxacin preparation |
| CN103768066A (en) * | 2012-10-22 | 2014-05-07 | 洛阳惠中兽药有限公司 | Quinolone pharmaceutical composition, and preparation and application methods thereof |
| CN104434811A (en) * | 2014-11-07 | 2015-03-25 | 浙江大学 | Drug sustained-release microsphere capable of being embedded in intraocular lens loop and preparation method of drug sustained-release microsphere |
| CN105078899A (en) * | 2015-08-26 | 2015-11-25 | 四川农业大学 | Enrofloxacin stratified high molecular taste mashing skeleton particle and preparation method thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104095829A (en) * | 2014-08-02 | 2014-10-15 | 佳木斯大学 | Preparation method for enrofloxacin chitosan microsphere |
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| DE19633480A1 (en) * | 1996-08-20 | 1998-02-26 | Bayer Ag | Orally administrable formulations of quinolone and naphthyridonecarboxylic acids |
| CN1457783A (en) * | 2003-05-17 | 2003-11-26 | 南昌弘益科技有限公司 | Sparxacin dripping pill for resisting bacterial infection and its preparing method |
| US20050136114A1 (en) * | 2003-12-19 | 2005-06-23 | Council Of Scientific And Industrial Research | Taste masked pharmaceutical compositions comprising bitter drug and pH sensitive polymer |
| CN100341510C (en) * | 2005-06-10 | 2007-10-10 | 冯莉萍 | 'Ennoxacin' micro-capsule, and its prepn. method |
| CN100360131C (en) * | 2006-01-24 | 2008-01-09 | 新昌国邦化学工业有限公司 | Production method of odor-masking enrofloxacin |
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2008
- 2008-03-31 CN CN2008100918516A patent/CN101273980B/en active Active
- 2008-03-31 WO PCT/CN2008/000632 patent/WO2008151502A1/en active Application Filing
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101965913A (en) * | 2010-10-20 | 2011-02-09 | 无锡正大畜禽有限公司 | Production method for tasteless enteric enrofloxacin microcapsules |
| CN103239422A (en) * | 2012-04-26 | 2013-08-14 | 浙江康德权科技有限公司 | Preparation method of smellless coated enrofloxacin preparation |
| CN103239422B (en) * | 2012-04-26 | 2015-07-08 | 浙江康德权科技有限公司 | Preparation method of smellless coated enrofloxacin preparation |
| CN103768066A (en) * | 2012-10-22 | 2014-05-07 | 洛阳惠中兽药有限公司 | Quinolone pharmaceutical composition, and preparation and application methods thereof |
| CN104434811A (en) * | 2014-11-07 | 2015-03-25 | 浙江大学 | Drug sustained-release microsphere capable of being embedded in intraocular lens loop and preparation method of drug sustained-release microsphere |
| CN105078899A (en) * | 2015-08-26 | 2015-11-25 | 四川农业大学 | Enrofloxacin stratified high molecular taste mashing skeleton particle and preparation method thereof |
| CN105078899B (en) * | 2015-08-26 | 2018-06-29 | 四川农业大学 | A kind of Enrofloxacin cladding macromolecule flavoring skeleton particle and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| KR101148501B1 (en) | 2012-05-25 |
| CN101273980B (en) | 2010-09-01 |
| WO2008151502A1 (en) | 2008-12-18 |
| KR20090122466A (en) | 2009-11-30 |
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Owner name: HINAPHARM PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HAINACHUAN PHARMACEUTICAL CO., LTD., FOSHAN CITY |
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| CP03 | Change of name, title or address |
Address after: 528515 Guangdong province Foshan Gaoming Cangjiang Industrial Park West Sand Water District Heyuan Yang Road Patentee after: Hinapharm Pharmaceutical Co., Ltd. Address before: 528515 Guangdong province Foshan Gaoming Cangjiang Industrial Park, west of red bayberry Patentee before: Hainachuan Pharmaceutical Co., Ltd., Foshan City |
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| C56 | Change in the name or address of the patentee |
Owner name: GUANGDONG HINAPHARM BIOTECHNOLOGY CO., LTD. Free format text: FORMER NAME: HINAPHARM PHARMACEUTICAL CO., LTD. |
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| CP01 | Change in the name or title of a patent holder |
Address after: 528515 Guangdong province Foshan Gaoming Cangjiang Industrial Park West Sand Water District Heyuan Yang Road Patentee after: GUANGDONG HINABIOTECH CO., LTD. Address before: 528515 Guangdong province Foshan Gaoming Cangjiang Industrial Park West Sand Water District Heyuan Yang Road Patentee before: Hinapharm Pharmaceutical Co., Ltd. |