CN103007287A - Application of rhamnolipid as oral medicine absorbent accelerant - Google Patents
Application of rhamnolipid as oral medicine absorbent accelerant Download PDFInfo
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- 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
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- FCBUKWWQSZQDDI-UHFFFAOYSA-N rhamnolipid Chemical compound CCCCCCCC(CC(O)=O)OC(=O)CC(CCCCCCC)OC1OC(C)C(O)C(O)C1OC1C(O)C(O)C(O)C(C)O1 FCBUKWWQSZQDDI-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 239000003814 drug Substances 0.000 title claims abstract description 45
- 230000002745 absorbent Effects 0.000 title claims abstract description 16
- 239000002250 absorbent Substances 0.000 title claims abstract description 16
- 229940079593 drug Drugs 0.000 claims abstract description 14
- 102000014914 Carrier Proteins Human genes 0.000 claims description 5
- 108010078791 Carrier Proteins Proteins 0.000 claims description 5
- 238000010521 absorption reaction Methods 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 230000008595 infiltration Effects 0.000 description 18
- 238000001764 infiltration Methods 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 15
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 14
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 11
- 239000001963 growth medium Substances 0.000 description 11
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 11
- TUFFYSFVSYUHPA-UHFFFAOYSA-M rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C(C=CC(N)=C2)C2=[O+]C2=C1C=CC(N)=C2 TUFFYSFVSYUHPA-UHFFFAOYSA-M 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000012981 Hank's balanced salt solution Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 229960003712 propranolol Drugs 0.000 description 7
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 5
- 229960002274 atenolol Drugs 0.000 description 5
- 239000003876 biosurfactant Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000024245 cell differentiation Effects 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 230000004640 cellular pathway Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 229940126701 oral medication Drugs 0.000 description 2
- 210000004279 orbit Anatomy 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
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.
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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 |
| WO2021030702A1 (en) * | 2019-08-14 | 2021-02-18 | Locus Ip Company, Llc | Drinkable supplement composition for improved health and hydration |
| WO2021030250A1 (en) * | 2019-08-10 | 2021-02-18 | Locus Ip Company, Llc | Methods for increasing the bioavailability of otc and pharmaceutical drugs |
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| 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 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
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| 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 |
| EP3658124A4 (en) * | 2017-07-27 | 2021-04-21 | Locus IP Company, LLC | COMPOSITIONS TO IMPROVE THE BIOAVAILABILITY OF PHARMACEUTICAL PRODUCTS, COMPLEMENTS 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 |
| WO2019023039A3 (en) * | 2017-07-27 | 2019-03-28 | 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 |
| US12194102B2 (en) | 2017-07-27 | 2025-01-14 | 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 | METHOD OF 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 HYDRATING |
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