CN103007287A - Application of rhamnolipid as oral medicine absorbent accelerant - Google Patents
Application of rhamnolipid as oral medicine absorbent accelerant Download PDFInfo
- Publication number
- CN103007287A CN103007287A CN2012103757921A CN201210375792A CN103007287A CN 103007287 A CN103007287 A CN 103007287A CN 2012103757921 A CN2012103757921 A CN 2012103757921A CN 201210375792 A CN201210375792 A CN 201210375792A CN 103007287 A CN103007287 A CN 103007287A
- Authority
- CN
- China
- Prior art keywords
- rhamnolipid
- medicine
- oral
- application
- absorbent
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an application of rhamnolipid as oral medicine absorbent accelerant. Oral absorption rate of various medicines can be improved by by using rhamnolipid with the amount of 20-1000mg/L; the absorption rate can be increased by 0.03-10 times; and the effect is remarkable.
Description
Technical field
The present invention relates to the biosurfactant technical field, relate in particular to a kind of rhamnolipid as the application of the short absorbent of drug oral.
Background technology
Biosurfactant is a kind of complex structure, the diversified surfactant of group, mainly by microorganisms.Biosurfactant easily is degraded and is own nontoxic, and its environment friendly and biocompatibility are all better, thereby has a wide range of applications in each fields such as environmental conservation, medication chemistry, food and agriculturals.The rhamnolipid that is connected into by the 1-2 bar fatty acid chain of a hydrophilic 1-2 rhamnose and lipophilic is one of biosurfactant of greatest concern.For example, rhamnolipid has the effect of the following aspects: (1) improves microorganism to the biodegradability of the insoluble organics such as aromatic hydrocarbons; (2) use as antibiotic: destroy the cell membrane of antibacterial, fungus etc., thereby suppress growth; (3) as food additive, promote the emulsifying of food etc.
Because administering mode is easy and production cost is lower, oral drugs are forms of the most normal employing in the pharmacotherapy.Some medicine is caused bioavailability poor owing to difficult by gastrointestinal absorption, has limited its oral application and uses the mode such as drug administration by injection instead.According to current research, thereby can improving medicine, absorption enhancer absorbs the oral administration biaavailability that improves medicine at gastrointestinal.But up to the present, only have the last of the ten Heavenly stems sodium to have entered first phase clinical, but should have the large defective of consumption by short absorbent.Other not yet enters the oral short absorbent of candidate or the damage gastrointestinal mucosal epithelial cell of clinical trial, or causes in the human body immunoreation also or expensive.Therefore, relative low toxicity, inexpensive and effectively short absorbent become study hotspot.
Although rhamnolipid has potential extensive use, have no it as the application report of the short absorbent of drug oral.The present invention adopts the equal friendly rhanolipid as biosurfactant of environment and health to be used for the raising of the oral administration biaavailability of medicine.
Summary of the invention
The object of the invention is to the deficiency for existing oral short absorbent, the application of a kind of rhamnolipid as the short absorbent of drug oral is provided.
The objective of the invention is to be achieved through the following technical solutions: a kind of rhamnolipid is as the application of the short absorbent of drug oral, and the mass percent concentration of rhamnolipid is higher than 90%, and the consumption of rhamnolipid in medicine is 20-1000mg/L.
Further, described rhamnolipid can be used as the oral short absorbent of lipotropy macromolecular drug, hydrophilic medicament or the medicine take the transport protein mediation as the master etc.
The invention has the beneficial effects as follows: the present invention can improve the oral administration biaavailability of medicine safely and effectively with the oral short absorbent of rhamnolipid as medicine.
The specific embodiment
The invention provides a kind of rhamnolipid product as the application of the short absorbent of oral drugs of multi-medicament.
1. used rhamnolipid has and is higher than 90% purity (mass percent concentration).
2. in experiment in vitro, at first adopt the detection of cellular level.Detailed process is as follows
Rhamnolipid adds in the culture medium or buffer that contains finite concentration medicine to be measured, and being added to cultivate has cell
One side of (or other cultivate cells), opposite side is placed blank culture medium or buffer, is placed in 37 ℃ of CO2 gas incubator shaken cultivation 0.5-4 hour.Carry out intensive sampling in not celliferous side during this time, replenish blank culture medium or the buffer of equal volume after each collected specimens, analyze the concentration of collected specimens, calculate thus the apparent infiltration coefficient of medicine to be measured.
In experiment in vitro, adopt the organ that exsomatizes to detect.Detailed process is as follows:
Rhamnolipid adds in the culture medium or buffer that contains finite concentration medicine to be measured, is added to the inboard of organ (such as the small intestinal intercept), and opposite side is placed blank culture medium or buffer, adopts the oxygen that contains 5%CO2 to carry out bubbling and cultivates 0.5-4 hour.Middle intensive collection begins the sample for blank culture medium or blank buffer one side, replenishes blank culture medium or the buffer of same volume after the collected specimens, calculates thus the apparent infiltration coefficient of medicine to be measured.
3. in vivo in the experiment, main adopt some laboratory animals commonly used to carry out, below concrete operation with mice as representative.
Main employing body weight is that the mice about 250g is subjects.All zoopery operations are all carried out in accordance with People's Republic of China's zoopery statutory regulations.Before the experiment, water is only fed in all fasting 12 hours of all mices.After the slight anesthesia of ether, after the method by gavage is mixed the medicine to be measured of the oral dose of routine and variable concentrations rhamnolipid to the mice administration, each concentration group establish ten parallel.
Be put into fast centrifugalize in the test tube that contains heparin respectively at adopting after 0,0.25,0.5,1,1.5,2,3,4,6,8 and 12 hour after the administration eye socket to get blood 0.5ml blood sample, the blood plasma that obtains after centrifugal is preserved under-20 ℃ of conditions and is used for analysis.To be analyzed go out blood drug level after, 100% blood drug level that absorbs that curve and intravenous injection obtain during by medicine calculates the oral administration biaavailability of medicine.
The remarkable result that particular content of the present invention is described in detail in detail and brings below in conjunction with specific embodiment.
Embodiment 1: at cellular level, the short phenol red cross-film of rhamnolipid absorbs
Phenol red can the representative with alternative pathway is absorbed as main hydrophilic medicament.These materials bioavailability under normal physiological conditions is extremely low, substantially belongs to difficult absorption level.Adopt the Caco-2 cell model to carry out the bioavailability experiment that rhamnolipid improves this medicine.Adopting the aperture is 3 microns
Cell is cultivated the Caco-2 cell, after cell differentiation is finished, the phenol red HBSS solution that contains that is added with the rhamnolipid of variable concentrations is added into the cell upside.The phenol red concentration among the HBSS of downside is measured in close sampling in 4 hours, calculates the phenol red apparent infiltration coefficient of the rhamnolipid that contains variable concentrations, can draw the data of table 1.
Table 1: rhamnolipid is on the impact of phenol red apparent infiltration coefficient
The above results shows, when its working concentration was 20mg/L, apparent infiltration coefficient only increased by 0.04 times, and when its working concentration is 400mg/L, apparent infiltration coefficient increases multiple and reaches 9.35, and the ability of the apparent infiltration coefficient that the increase of visible rhamnolipid is phenol red is outstanding.Embodiment 2: at cellular level, the cross-film that adopts rhamnolipid to increase Propranolol absorbs
Testing used Propranolol is to wear cellular pathways to be absorbed as main lipotropy macromolecular drug, and its bioavailability under normal physiological conditions is relatively high.Adopt the Caco-2 cell model to carry out the bioavailability experiment that rhamnolipid improves this medicine.Adopting the aperture is 3 microns
Cell is cultivated the Caco-2 cell, after cell differentiation is finished, the HBSS solution that contains Propranolol that is added with the rhamnolipid of variable concentrations is added into the cell upside.The concentration of the Propranolol among the HBSS of downside is measured in close sampling in 4 hours, calculates the apparent infiltration coefficient of the Propranolol of the rhamnolipid that contains variable concentrations, can draw the data of table 2.
Table 2: rhamnolipid is on the impact of the apparent infiltration coefficient of Propranolol
The above results shows, when its working concentration is 20mg/L, apparent infiltration coefficient only increase by 0.03 times almost constant, and when its working concentration is 400mg/L, apparent infiltration coefficient increase multiple also only is 0.62.Although it is limited that effect increases, consider that the oral absorption of Propranolol itself is just very high, so can think that rhamnolipid is to wear the cellular pathways sorbefacient effect certain as the principal agent thing also has.
Embodiment 3: at cellular level, rhamnolipid suppresses effluxing of rhodamine
Testing used Rhodamine 123 is that the transport protein mediation is main, can represent take the transport protein mediation as main medicine.Observe rhamnolipid to the bioavailability experiment of this type of medicine at the Caco-2 cell model.Adopting the aperture is 3 microns
Cell is cultivated the Caco-2 cell, after cell differentiation is finished, the HBSS solution that contains Rhodamine 123 that is added with the rhamnolipid of variable concentrations is added into the cell upside.The concentration of the Rhodamine 123 among the HBSS of downside is measured in close sampling in 4 hours, calculates the apparent infiltration coefficient of the Rhodamine 123 of the rhamnolipid that contains variable concentrations.In like manner, above-mentioned Rhodamine 123 solution is added into the cell downside, measures the time dependent concentration of Rhodamine 123 among the HBSS of upside, calculate the apparent infiltration coefficient of the Rhodamine 123 of this direction.Draw the data of table 3.Table 3: rhamnolipid is on the impact of the two-way transhipment of Rhodamine 123
The above results shows, when its working concentration is 20mg/L, ratio significantly descends, drop to 4.32 constant from 8.4, and when its working concentration is 150mg/L, outer parallelism also is reduced to 1.88 level, illustrates substantially to have suppressed effluxing of Rhodamine 123, and visible rhamnolipid is to take the transport protein mediation sorbefacient effect certain as the principal agent thing also has.
Embodiment 4: in the isolated organ level, adopt rhamnolipid to increase phenol red bioavailability
Rhamnolipid adds to and contains in the finite concentration phenol red culture medium or buffer, is added to the inboard of organ (such as the small intestinal intercept), and opposite side is placed blank culture medium or buffer, adopts the oxygen that contains 5%CO2 to carry out bubbling and cultivates 0.5-4 hour.Middle intensive collection begins the sample for blank culture medium or blank buffer one side, replenishes blank culture medium or the buffer of same volume after the collected specimens, calculates thus the apparent infiltration coefficient of medicine to be measured.The result is as shown in table 4:
Table 4: rhamnolipid is on the phenol red impact that sees through the apparent infiltration coefficient of little intestinal segment
The above results shows, when its working concentration was 20mg/L, apparent infiltration coefficient only increased by 0.01 times, and when its working concentration is 1000mg/L, apparent infiltration coefficient increases multiple and reaches 4.40, and the ability of the apparent infiltration coefficient that the increase of visible rhamnolipid is phenol red is outstanding
Embodiment 5: in the animal level, adopt rhamnolipid to increase the bioavailability of atenolol
The Wistar mice that main employing is provided by the Zhejiang Academy of Medical Sciences is about 100g.All zoopery operations are all carried out in accordance with People's Republic of China's zoopery statutory regulations.Before the experiment, water is only fed in all fasting 12 hours of all mices.After the slight anesthesia of ether, after the method by gavage is mixed 0.5mg/kg and variable concentrations rhamnolipid to the mice administration, each concentration group establish ten parallel.
Be put into fast centrifugalize in the test tube that contains heparin respectively at adopting after 0,0.25,0.5,1,1.5,2,3,4,6,8 and 12 hour after the administration eye socket to get blood 0.5ml. blood sample, the blood plasma that obtains after centrifugal is preserved under-20 ℃ of conditions and is used for analysis.Method by high performance liquid chromatography is measured the concentration of atenolol, and 100% blood drug level that absorbs that curve and intravenous injection obtain during by medicine calculates the oral administration biaavailability of medicine, the results are shown in Table 5.
Table 5: rhamnolipid is to the variation of the bioavailability of the oral atenolol of mice
The above results shows, when working concentration is 100mg/L, the oral administration biaavailability of atenolol has slight lifting, when the concentration of rhamnolipid reaches 1000mg/L, the oral administration biaavailability that can improve atenolol can increase by 50%, and the visible rhamnolipid in vivo ability of the oral administration biaavailability of the level rise medicine is also comparatively outstanding.
Above-described embodiment is used for the present invention that explains, rather than limits the invention, and in the protection domain of spirit of the present invention and claim, any modification and change to the present invention makes all fall into protection scope of the present invention.
Claims (2)
1. the application that rhamnolipid is urged absorbent as drug oral is characterized in that the mass percent concentration of rhamnolipid is higher than 90%, and the consumption of described rhamnolipid in medicine is 20-1000 mg/L.
2. according to claim 1 described application is characterized in that, described rhamnolipid can be used as the oral short absorbent of lipotropy macromolecular drug, hydrophilic medicament or the medicine take the transport protein mediation as the master etc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103757921A CN103007287A (en) | 2012-09-29 | 2012-09-29 | Application of rhamnolipid as oral medicine absorbent accelerant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103757921A CN103007287A (en) | 2012-09-29 | 2012-09-29 | Application of rhamnolipid as oral medicine absorbent accelerant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103007287A true CN103007287A (en) | 2013-04-03 |
Family
ID=47956749
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012103757921A Pending CN103007287A (en) | 2012-09-29 | 2012-09-29 | Application of rhamnolipid as oral medicine absorbent accelerant |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103007287A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107375221A (en) * | 2017-07-12 | 2017-11-24 | 广州富诺健康科技股份有限公司 | One kind contains farnoquinone calcium tablet and preparation method thereof |
| WO2019023039A3 (en) * | 2017-07-27 | 2019-03-28 | Locus Ip Company, Llc | Compositions for enhancing bioavailability of pharmaceuticals, supplements and ingested substances |
| WO2019133313A1 (en) * | 2017-12-28 | 2019-07-04 | Locus Ip Company, Llc | Oral health composition comprising purified biosurfactants and/or their derivatives |
| WO2021030250A1 (en) * | 2019-08-10 | 2021-02-18 | Locus Ip Company, Llc | Methods for increasing the bioavailability of otc and pharmaceutical drugs |
| WO2021030702A1 (en) * | 2019-08-14 | 2021-02-18 | Locus Ip Company, Llc | Drinkable supplement composition for improved health and hydration |
| US11890341B2 (en) | 2019-05-10 | 2024-02-06 | Locus Solutions Ipco, Llc | Compositions and methods for treating biofilm-related lung conditions |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4902512A (en) * | 1987-01-22 | 1990-02-20 | Director-General Of Agency Of Industrial Science And Technology And Shin-Etsu Chemical Co., Ltd. | Rhamnolipid liposomes |
| CN101695645A (en) * | 2009-11-09 | 2010-04-21 | 湖南大学 | Reverse micelle as well as preparation method and application to cellulose enzymolysis thereof |
-
2012
- 2012-09-29 CN CN2012103757921A patent/CN103007287A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4902512A (en) * | 1987-01-22 | 1990-02-20 | Director-General Of Agency Of Industrial Science And Technology And Shin-Etsu Chemical Co., Ltd. | Rhamnolipid liposomes |
| CN101695645A (en) * | 2009-11-09 | 2010-04-21 | 湖南大学 | Reverse micelle as well as preparation method and application to cellulose enzymolysis thereof |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107375221A (en) * | 2017-07-12 | 2017-11-24 | 广州富诺健康科技股份有限公司 | One kind contains farnoquinone calcium tablet and preparation method thereof |
| WO2019023039A3 (en) * | 2017-07-27 | 2019-03-28 | Locus Ip Company, Llc | Compositions for enhancing bioavailability of pharmaceuticals, supplements and ingested substances |
| CN111148511A (en) * | 2017-07-27 | 2020-05-12 | 轨迹Ip有限责任公司 | Composition for improving bioavailability of drugs, supplements and ingested substances |
| EP3658124A4 (en) * | 2017-07-27 | 2021-04-21 | Locus IP Company, LLC | Compositions for enhancing bioavailability of pharmaceuticals, supplements and ingested substances |
| US11590231B2 (en) * | 2017-07-27 | 2023-02-28 | Locus Solutions Ipco, Llc | Compositions for enhancing bioavailability of pharmaceuticals, supplements and ingested substances |
| WO2019133313A1 (en) * | 2017-12-28 | 2019-07-04 | Locus Ip Company, Llc | Oral health composition comprising purified biosurfactants and/or their derivatives |
| US11964040B2 (en) | 2017-12-28 | 2024-04-23 | Locus Solutions Ipco, Llc | Oral health composition comprising purified biosurfactants and/or their derivatives |
| US11890341B2 (en) | 2019-05-10 | 2024-02-06 | Locus Solutions Ipco, Llc | Compositions and methods for treating biofilm-related lung conditions |
| WO2021030250A1 (en) * | 2019-08-10 | 2021-02-18 | Locus Ip Company, Llc | Methods for increasing the bioavailability of otc and pharmaceutical drugs |
| EP4009954A4 (en) * | 2019-08-10 | 2023-07-26 | Locus IP Company, LLC | Methods for increasing the bioavailability of otc and pharmaceutical drugs |
| WO2021030702A1 (en) * | 2019-08-14 | 2021-02-18 | Locus Ip Company, Llc | Drinkable supplement composition for improved health and hydration |
| EP4013429A4 (en) * | 2019-08-14 | 2023-08-16 | Locus IP Company, LLC | Drinkable supplement composition for improved health and hydration |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103007287A (en) | Application of rhamnolipid as oral medicine absorbent accelerant | |
| CN102586393A (en) | Microbial limit detection method of miconazole nitrate suppository | |
| CN105726522B (en) | Magnolol is killing application and its preparation in fish parasitic protozoa | |
| CN104357355A (en) | Bacillus natto capable of producing MK-7 and application of bacillus natto | |
| CN103520157B (en) | Application of combination of tacrolimus and fluconazole in preparing antifungal drugs | |
| CN111329835A (en) | Clindamycin phosphate injection and preparation method thereof | |
| CN101390869A (en) | Use of high-purity forsythin in preparing bacteriostasis, antivirus and other medicine | |
| CN103897691B (en) | The In vivo detection probe of bacteriological infection early diagnosis | |
| CN106674331B (en) | Antibacterial lipopeptide bacaucin and preparation method and application thereof | |
| Turło et al. | Biological availability and preliminary selenium speciation in selenium-enriched mycelium of Lentinula edodes (berk.) | |
| CN103911422A (en) | Sterility testing method of antifungal pharmaceutical preparation | |
| CN104046584A (en) | Bifidobacterium adolescentis bacteriocin as well as production method and special production strain of bifidobacterium adolescentis bacteriocin | |
| CN104193686B (en) | N-Galla Turcica (Galla Helepensis) amide-pyrimidine radicals benzsulfamide analog derivative and its preparation method and application | |
| CN102772359A (en) | Enrofloxacin injection and preparation method thereof | |
| CN105663126A (en) | Antifungal product combining ambroxol hydrochloride with fluconazole and application thereof | |
| CN113908121A (en) | Niclosamide injection and preparation and application thereof | |
| CN103651358B (en) | Tea saponin granule, as well as preparation method and use thereof | |
| CN103157104A (en) | Sodium thiosulfate diluent of swine fever vaccine | |
| CN105960408A (en) | Novel microbial product having antifungal activity | |
| CN108315386A (en) | A kind of desorption agent prescription and preparation method thereof of Cyclops of Zooplankton body surface particle-bound bacteria detection | |
| CN113181229B (en) | Application of cabbage type rape-isatis tinctoria G monomer addition system in inhibiting novel coronavirus SARS-CoV-2 | |
| CN104610281B (en) | Ceftiofur magnesium and preparation and application thereof | |
| CN1218704C (en) | Sodium bialginate for injection and its preparation method | |
| CN103536593A (en) | Use of pyrroloquinoline quinone in preparing medicines for preventing and treating tumors | |
| CN102846592A (en) | Medical compound containing borneol |
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 |
Application publication date: 20130403 |