CN1669567A - Rough gentian soft capsule for treating hepatic diseases - Google Patents
Rough gentian soft capsule for treating hepatic diseases Download PDFInfo
- Publication number
- CN1669567A CN1669567A CN 200410008687 CN200410008687A CN1669567A CN 1669567 A CN1669567 A CN 1669567A CN 200410008687 CN200410008687 CN 200410008687 CN 200410008687 A CN200410008687 A CN 200410008687A CN 1669567 A CN1669567 A CN 1669567A
- Authority
- CN
- China
- Prior art keywords
- radix gentianae
- soft capsule
- extract
- suspending agent
- diluent
- 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.)
- Granted
Links
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The disclosed soft capsule preparation comprises Chinese gentian extractive and medicinal adjuvant, the active constituents of the Chinese gentian extractive includes gentiopicrin, while the medicinal adjuvant includes deflocculating agent and suspension auxiliary agent. The capsule shell is prepared mainly from gelatin and glycerine. The medicament granule is prepared through a pressing process.
Description
Technical field
The present invention relates to a kind of Radix Gentianae soft capsule for the treatment of hepatopathy.
Background technology
Radix Gentianae is the Gentianaceae gentian, has heat clearing and damp drying, the effect of eliminating pathogen in the liver gallbladder fire.Based on the Chinese medicine compound of Radix Gentianae, aspect the treatment acute and chronic hepatitis, obtained good effect at home.The main component of Radix Gentianae is a gentiopicrin, discovers that gentiopicrin can be used for treating acute icterohepatitis and chronic active hepatitis.The patent application of application number 01126701 discloses a kind of application that contains Chinese medicine preparation, preparation method and the said preparation of gentiopicroside as preparation treatment liver disease drug, has wherein proposed Radix Gentianae activity extract and pharmaceutic adjuvant are made the capsular method of solid preparation.But, after Radix Gentianae extract is made common solid orally ingestible as middle extract,, be difficult to reach the clinical efficacy of expection because its poorly water-soluble causes oral post-absorption relatively poor, thereby blood drug level is exerted an influence.
Soft capsule compare with general formulation have the bioavailability height, good seal, content accurately, characteristic such as good looking appearance, very suitable for the hydrophobic drug of bioavailability difference.Therefore, soft capsule that Radix Gentianae extract and macromolecule carrier are packed into after miscible can disintegrate fast in digestive tract after oral, and the medicinal liquid after the disintegrate adheres to tissue surface rapidly widely, promotes absorption of active agents, thereby increases substantially its bioavailability.Test confirms, the bioavailability of several peroral dosage forms is best with the soft capsule of solution shape content.In addition, soft capsule is because of its unique embedding and cover effect, can also reduce the zest of medicine.
Summary of the invention
The present invention be directed to the deficiencies in the prior art and finish, its objective is provides a kind of Radix Gentianae soft capsule for the treatment of hepatopathy.The inventor is through further investigation, found that, the ratio of Radix Gentianae extract, diluent and suspending agent by will forming Radix Gentianae soft capsule medicine liquid ingredient is set within the specific limits, can obtain a kind ofly being easy to make, bioavailability height, good seal, content accurately, convenient drug administration, Radix Gentianae soft capsule that the effective ingredient stripping is fast.
The Radix Gentianae soft capsule that the present invention proposes, be made of medicinal liquid and softgel shell two parts, wherein, medicinal liquid contains the Radix Gentianae active component extract of effective dose and is equipped with pharmaceutic adjuvant, pharmaceutic adjuvant mainly comprises diluent and suspending agent, also comprises emulsifying agent, antioxidant etc.Softgel shell mainly is made up of gelatin and glycerol, and is added with an amount of antiseptic and lucifuge agent.
Radix Gentianae extract among the present invention can adopt general known extracting method to be prepared.Find that after deliberation Different Extraction Method and extraction conditions can influence the content of gentiopicrin active component in the Radix Gentianae extract.Provided the gentiopicrin content that uses different concentration ethanol to obtain in the following table 1 through Different Extraction Method.
Table 1 different concentration ethanol and extracting method are relatively
| Concentration of alcohol (%) | Extracting method | Gentiopicrin content (%) in the extract |
| ????95 | Cold-maceration | ?????8.115 |
| ????70 | Cold-maceration | ?????9.490 |
| ????50 | Cold-maceration | ?????9.181 |
| ????95 | Heat reflow method | ?????6.852 |
| ????70 | Heat reflow method | ?????8.808 |
| ????50 | Heat reflow method | ?????7.049 |
The gentiopicrin content that adopts cold-maceration to extract in the Radix Gentianae extract that obtains with 70% ethanol is the highest as seen from the above table.
Diluent of the present invention can use and be selected from Polyethylene Glycol, propylene glycol, glycerol, vegetable oil, the mineral oil one or more, preferably vegetable oil, special preferably corn oil and soybean oil, more preferred soybean oil.
Suspending agent can use and be selected from soybean phospholipid, Cera Flava, aluminum monostearate, methylcellulose, ethyl cellulose, hydroxyethyl-cellulose, chitin, chitose, Carboxymethyl cellulose sodium, agar, hydroxypropyl cellulose, xanthan gum, arabic gum, casein, carbomer, polyvinyl alcohol, the sodium alginate one or more.Preferred soybean phospholipid.
Antioxidant can use and be selected from ethylenediaminetetraacetic acid, disodium EDTA, dibenzylatiooluene, glycine, inositol, ascorbic acid, lecithin, malic acid, hydroquinone, citric acid, the succinic acid one or more.
Emulsifying agent can use and be selected from ethylhydroxyethylcellulose, methylcellulose, glyceryl monostearate, hydrolecithin, acetylated monoglyceride, orthoformic acid, casein, ethylene glycol monostearate, diacetyl monoglyceride, acetic acid one fatty glyceride, Emulsifier LM-102, the propylene glycol alginate one or more.
Antiseptic can use and be selected from nipalgin lactone (methyl ester, ethyl ester), sorbic acid, Sodium Methyl Hydroxybenzoate, benzoic acid, sorbic acid methyl ester, methyl parahydroxybenzoate, P-hydroxybenzoic acid phenyl ester, butyl p-hydroxybenzoate calcium, Oleum Caryophylli, benzyl alcohol, the Sodium Propyl Hydroxybenzoate one or more.
Because Radix Gentianae extract is pressed powder, the diluent addition is unsuitable very few, otherwise thickness too makes troubles for the rolling of soft capsule.Add diluent according to table 2 ratio, observe character, the result is as shown in table 1.
The amount ratio of table 2 extract and diluent is to the influence of medicinal liquid character
| Extract and diluent amount ratio (weight ratio) | Character |
| ??????1∶1 | Very thickness, mobile extreme difference |
| ??????1∶2 | Than thickness, mobile relatively poor |
| ??????1∶3 | Better mobile |
| ??????1∶4 | Good fluidity |
| ??????1∶5 | Good fluidity |
| ??????1∶6 | Good fluidity, but extractive content reduces |
By The above results as can be known, the weight ratio of Radix Gentianae extract and diluent is preferably 1: 3～and 6, most preferably be 1: 4～5.
In addition,, can't be dissolved in the various oil, therefore need to add suitable suspending agent, make suspension because Radix Gentianae extract is not oil-soluble.Above-mentioned those of the optional usefulness of suspending agent can increase the material of disperse medium viscosity, as soybean phospholipid, Cera Flava, aluminum monostearate, ethyl cellulose etc., preferably use soybean phospholipid.
For determining the ratio of Radix Gentianae extract and suspending agent, carried out following test: 10g Radix Gentianae extract and 40g soybean oil are mixed, make 3 parts altogether, add soybean phospholipid 0.5g, 0.8g, 1.0g respectively, place the identical graduated cylinder of diameter to stir, measure the original height (H of disperse system
0) and through leaving standstill the height (H of back precipitum
u), H
u/ H
0Be settling ratio F, the F value is big more, and content suspendible system is stable more, and the result is as shown in table 3.
The consumption of table 3 suspending agent is to the influence (is example with the soybean phospholipid) of settling ratio F
| Numbering | Settling ratio (F) |
| 1 (soybean phospholipid 0.6g) | ????0.68 |
| 2 (soybean phospholipid 0.8g) | ????0.83 |
| 3 (soybean phospholipid 1.0g) | ????0.90 |
By above result as can be known, when adding 0.6g, 0.8g, 1.0g soybean phospholipid in the mixture of every 10g Radix Gentianae extract and 40g soybean oil respectively, all can obtain good settling ratio.The settling ratio of settling ratio when adding the 1.0g soybean phospholipid differs and not quite when adding the 0.8g soybean phospholipid, and the former be enough to guarantee loading amount when soft capsule is rolling evenly, accurately.
Therefore, each constituent content is selected as follows by weight in the medicinal liquid of Radix Gentianae soft capsule of the present invention:
Radix Gentianae extract: diluent: suspending agent=1: 3～6: 0.05～0.10.
The preferred weight ratio of the medicinal liquid component of Radix Gentianae soft capsule of the present invention is as follows:
Radix Gentianae extract: diluent: suspending agent=1: 4～5: 0.06～0.10.
The most preferably weight ratio of the medicinal liquid component of Radix Gentianae soft capsule of the present invention is as follows:
Radix Gentianae extract: diluent: suspending agent=1: 4: 0.08.
Radix Gentianae soft capsule shell component of the present invention comprises gelatin, glycerol, antiseptic, lucifuge agent etc.The weight ratio of gelatin and glycerol is about 1: 0.3.The component and the content of every softgel shell are as follows:
Component gram/grain
Gelatin 0.10-0.40
Glycerol 0.03-0.15
Antiseptic 0.00001-0.00005
Lucifuge agent 0.001-0.005
Because it is very crucial to soft capsule production that soft capsule shell is formed, be directly connected to the molding of soft capsule and attractive in appearance.The design of employing orthogonal experiment, with the disintegration of making soft capsule is index, proportioning between gelatin, glycerol, the water three is optimized selection, gelatin and glycerol ratio, water and gelatin ratio two factors have significant difference (P＜0.05) as a result, melten gel temperature there was no significant difference, final definite gelatin: glycerol: water is 2: 1: 2, the best when the melten gel temperature is 70 ℃.Can also add an amount of disintegrating agent (for example Polyethylene Glycol) in the capsule shells, can mix with glue and be easy to absorb, can quicken the disintegrate of softgel shell.
Description of drawings
Fig. 1 is the technological process of preparation Radix Gentianae extract.
Fig. 2 is one of the technological process of a preparation Radix Gentianae soft capsule example.
The specific embodiment
(preparation of Radix Gentianae extract)
Shown in the process chart that Fig. 1 provides, the extracting method of Radix Gentianae extract of the present invention may further comprise the steps: and pulverizing → ethanol lixiviate → concentrate → resin column chromatography → washing → alcohol washes → and vacuum decompression is concentrated → spray drying.Particularly, with Radix Gentianae coarse powder (dry root), with 70% ethanol extraction secondary, the ethanol that adds for the first time 8～15 times of amounts, extracted 2 hours, add for the second time the ethanol of 5～10 times of amounts, extracted 1 hour, merge ethanol extract, decompression recycling ethanol to every Hydrargyri Oxydum Rubrum liquid contains crude drug 0.3～0.5kg, (upper prop dose (weight) is 1～5: 3～10 (W: V)) with the ratio of amount of resin (volume) to last AB-8 (or SP825) macroporous adsorptive resins, and water-solubility impurity is removed in first water flushing, uses 50% alcohol flushing then, collect eluent, decompression recycling ethanol to proportion is 1.05, and spray drying, inlet temperature are 165-180 ℃, leaving air temp is 75-85 ℃, obtain yellow Radix Gentianae extract powder, measure total gentiopicrin content in every cron gall extract, the result is for being higher than 300mg.
(preparation of soft capsule)
Soft capsule is made up of two parts: softgel shell and capsule 's content.Flow chart shown in Figure 2 has provided an example of preparation soft capsule preparation of the present invention.
Radix Gentianae soft capsule of the present invention can prepare as stated above, provided concrete one-tenth among the following embodiment and be grouped into, but protection scope of the present invention is not limited thereto.
The Radix Gentianae preparation of soft capsule method of the present invention of Cai Yonging comprises the steps: in the following embodiments
1. prepare the softgel shell glue: getting the nipalgin lactone is 16% with ethanol dilution to concentration, soaked in the lump 2 hours with gelatin, glycerol, red ferric oxide, gelatin is expanded, put then and be heated to 65 ℃ in the glue pot, mix homogeneously, be evacuated to and do not have bubble, with 100 order stainless steel sift net filtrations, filtrate is put and is placed in the glue-storing barrel 3～4 hours (keeping 50 ℃ of temperature), makes the foam come-up, scrape off the foam of come-up, heat preservation for standby use.
2. in proportion Radix Gentianae extract is mixed with diluent, suspending agent, put and grind in the colloid mill evenly, to the 1-5 micron.
3. above-mentioned capsule 's content and softgel shell glue are rolled into soft capsule through encapsulating machine.
Embodiment
Embodiment 1
Composition weight (gram/grain)
Radix Gentianae extract 0.1
Soybean oil 0.4
Soybean phospholipid 0.008
Gelatin 0.25
Glycerol 0.085
Red ferric oxide 0.0038
Nipalgin lactone 0.002
Embodiment 2
Composition weight (gram/grain)
Radix Gentianae extract 0.2
Semen Maydis oil 0.8
Lecithin 0.016
Gelatin 0.20
Glycerol 0.07
Benzoic acid 0.001
Embodiment 3
Composition weight (gram/grain)
Radix Gentianae extract 0.2
Oleum Arachidis hypogaeae semen 1.2
Soybean phospholipid 0.024
Glycerol 0.06
Gelatin 0.18
Diacetyl monoglyceride 0.001
Embodiment 4
Composition weight (gram/grain)
Radix Gentianae extract 0.01
Oleum Sesami 0.02
Methylcellulose 0.002
Glycerol 0.06
Gelatin 0.18
Cera Flava 0.02
Benzoic acid 0.0002
The dissolution test:
Dissolution medium: water
Temperature: 37 ± 2 ℃
Rotating speed: 50 rev/mins
Sample volume: 10ml
Detection method: HPLC
Table 4 dissolution result of the test
| Sample dissolution rate (%) | Time (minute) | ||
| ????15 | ????30 | ????45 | |
| Embodiment 1 | ????5 | ????80 | ????100 |
| Embodiment 2 | ????5 | ????78 | ????100 |
| Embodiment 3 | ????10 | ????80 | ????100 |
| Embodiment 4 | ????5 | ????70 | ????100 |
As shown in Table 4, the stripping in the time of 15 minutes is lower, be the soft capsule disintegrate slow slightly due to, after 30 minutes stripping bigger, when the content viscosity is low (embodiment 3), can improve the dissolution at initial stage.
In addition,, make Radix Gentianae extract the content tablet and the hard capsule of (every gram extract contains gentiopicrin 300mg) identical with the soft capsule of above-mentioned preparation by well-established law respectively, carry out the release contrast test in simulated gastric fluid for contrasting.The result is as shown in the table.
The release of table 5 different dosage form
| Dissolution (%) | Time (branch) | |||||
| ???5 | ????10 | ????20 | ????30 | ????45 | ????60 | |
| Tablet | ???10 | ????15 | ????20 | ????25 | ????50 | ????80 |
| Hard capsule | ???15 | ????20 | ????25 | ????35 | ????70 | ????80 |
| Soft capsule (preparation among the embodiment 1) | ???0 | ????0 | ????80 | ????100 | ????- | ????- |
The AUC:100 μ g.min/ml of tablet
Hard capsule AUC:200 μ g.min/ml
Soft capsule AUC:600 μ g.min/ml
By the result as can be known, the AUC value of soft capsule can more effectively be brought into play the drug action of gentiopicrin apparently higher than tablet and hard capsule.
Sample stability
Get the soft capsule of embodiment 1 preparation, (aluminium foil/PVC) place temperature is 40 ℃, and relative humidity is to carry out accelerated test 6 months under 65% the condition according to commercially available back, check outward appearance, measure content and dissolution, test shows that the Radix Gentianae soft capsule quality is stable, the results are shown in Table 6.
Table 6 stability test result
| Time (moon) | Character | Content (mg/ grain) | Dissolution (30 minutes, labelled amount %) |
| ????0 | Softgel shell is soft, not being aged | ????25.64 | ????80 |
| ????1 | Softgel shell is soft, not being aged | ????25.72 | ????80 |
| ????2 | Softgel shell is soft, not being aged | ????25.86 | ????80 |
| ????3 | Softgel shell is soft, not being aged | ????25.78 | ????80 |
| ????6 | Softgel shell is soft, not being aged | ????25.81 | ????80 |
By the result as can be known, soft capsule preparation of the present invention after 6 months accelerated test, excellent in stability.
In sum, the invention provides a kind of Radix Gentianae soft capsule for the treatment of hepatopathy, the ratio of Radix Gentianae extract, diluent and suspending agent by will forming Radix Gentianae soft capsule medicine liquid ingredient is set within the specific limits, can obtain a kind ofly being easy to make, bioavailability height, good seal, content accurately, convenient drug administration, Radix Gentianae soft capsule that the effective ingredient stripping is fast.
Claims (5)
1. a Radix Gentianae soft capsule for the treatment of hepatopathy is made of medicinal liquid and softgel shell two parts, it is characterized in that medicinal liquid contains the Radix Gentianae active component extract of effective dose, and is equipped with pharmaceutic adjuvant, and pharmaceutic adjuvant mainly comprises diluent and suspending agent.
2. Radix Gentianae soft capsule as claimed in claim 1 is characterized in that each constituent content is by weight being Radix Gentianae extract in the medicinal liquid: diluent: suspending agent=1: 3～6: 0.05～0.10.
3. Radix Gentianae soft capsule as claimed in claim 2 is characterized in that each constituent content is by weight being Radix Gentianae extract in the medicinal liquid: diluent: suspending agent=1: 4～5: 0.06～0.10.
4. Radix Gentianae soft capsule as claimed in claim 3, it is characterized in that described diluent is selected from Polyethylene Glycol, propylene glycol, glycerol, vegetable oil and mineral oil, described suspending agent is selected from soybean phospholipid, Cera Flava, aluminum monostearate, methylcellulose, ethyl cellulose, hydroxyethyl-cellulose, chitin, chitose, Carboxymethyl cellulose sodium, agar, hydroxypropyl cellulose, xanthan gum, arabic gum, casein, carbomer, polyvinyl alcohol and sodium alginate.
5. Radix Gentianae soft capsule as claimed in claim 4 is characterized in that described vegetable oil is a soybean oil, and described suspending agent is a soybean phospholipid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200410008687XA CN100409860C (en) | 2004-03-16 | 2004-03-16 | Rough gentian soft capsule for treating hepatic diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200410008687XA CN100409860C (en) | 2004-03-16 | 2004-03-16 | Rough gentian soft capsule for treating hepatic diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1669567A true CN1669567A (en) | 2005-09-21 |
| CN100409860C CN100409860C (en) | 2008-08-13 |
Family
ID=35041144
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB200410008687XA Expired - Fee Related CN100409860C (en) | 2004-03-16 | 2004-03-16 | Rough gentian soft capsule for treating hepatic diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100409860C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085238B (en) * | 2009-12-08 | 2012-11-14 | 复旦大学 | Lipid preparation containing radix gentianae totalglycoside-phospholipid complexes and preparation method thereof |
| CN106692500A (en) * | 2015-11-18 | 2017-05-24 | 珠海宝德润生健康科技有限公司 | Composition for enhancing immunity and preparation method thereof |
| CN108703955A (en) * | 2018-07-31 | 2018-10-26 | 荆楚理工学院 | A kind of minerals soft capsule and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1202839C (en) * | 2001-09-07 | 2005-05-25 | 娄如菊 | Chinese medicine prepn for treating hepatosis and its prepn process |
-
2004
- 2004-03-16 CN CNB200410008687XA patent/CN100409860C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085238B (en) * | 2009-12-08 | 2012-11-14 | 复旦大学 | Lipid preparation containing radix gentianae totalglycoside-phospholipid complexes and preparation method thereof |
| CN106692500A (en) * | 2015-11-18 | 2017-05-24 | 珠海宝德润生健康科技有限公司 | Composition for enhancing immunity and preparation method thereof |
| CN108703955A (en) * | 2018-07-31 | 2018-10-26 | 荆楚理工学院 | A kind of minerals soft capsule and preparation method thereof |
| CN108703955B (en) * | 2018-07-31 | 2020-02-21 | 荆楚理工学院 | Mineral soft capsule and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100409860C (en) | 2008-08-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1091368C (en) | Pharmaceutical composition comprising coenzyme Q10 | |
| CN1213754C (en) | Beta-carboline pharmaceutical compositions | |
| CN1939305A (en) | Cephalofruxin ester liposome, its preparation and medicinal composition containing it | |
| CN1669567A (en) | Rough gentian soft capsule for treating hepatic diseases | |
| CN1785203A (en) | Astragaloside cyclodextrin clathrate, its prepn. and preparing mehtod | |
| CN1085674C (en) | Safflower total uranidin, its preparation and application | |
| CN1543943A (en) | Oral silybin sustained release agent and preparation thereof | |
| CN1775271A (en) | Hyperfunction-inhibiting preparation and new preparing method | |
| CN100341495C (en) | Solid dispersion and preoral combination of glibenclamide and preparation method | |
| CN1634428A (en) | Ginkgo leaf soft capsule and preparation technique thereof | |
| CN1891256A (en) | Red sage root dispersible tablet for treating cornary heart diseae and its preparing method | |
| CN1309379C (en) | Asari dripping pills and its preparation process | |
| CN1839849A (en) | Cucurbitacin soft capsule and its preparation process | |
| CN1718578A (en) | Lerivisiticum extract, its preparation method and medicine containing said extract | |
| CN1330537A (en) | Pharmaceutical mixed comprising profen | |
| CN1919214A (en) | Monascus soft capsule and its preparation method | |
| CN1294902C (en) | Cough and asthma relieving drop pills prepared using dahurian rhododendron leaf | |
| CN1706403A (en) | Self microemulsion of total dragon's blood flavone | |
| CN1296042C (en) | Acetyl salicyl sulfonone oral cavity disintegration tablet and its preparation method | |
| CN1535972A (en) | New compound,its preparation method, medicine preparation using said compound as active component, its action and application | |
| CN1823863A (en) | Panacea grass soft capsule and its production method | |
| CN1857233A (en) | Medicine composition soft capsule and its preparing process | |
| CN1284529C (en) | Compound gastrodia elata drop pills | |
| CN1543942A (en) | Haw leaf general flavone soft capsule and preparation thereof | |
| CN1430965A (en) | Soft capsule of puerarin and preparing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20171101 Address after: 100071 4056A room, No. 16, No. 9, Feng Feng pipeline, Beijing, Fengtai District Patentee after: Beijing Gangji Medical Technology Co., Ltd. Address before: 110013 Liaoning province Shenyang city Shenhe district municipal road 262 a base Torch Hotel Patentee before: Shenyang Tianrui Bio-Tech Development Co., Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080813 Termination date: 20210316 |