GB2463530A - The extraction of pharmacological agents from medicinal herbs using subcritical water - Google Patents
The extraction of pharmacological agents from medicinal herbs using subcritical water Download PDFInfo
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- GB2463530A GB2463530A GB0817353A GB0817353A GB2463530A GB 2463530 A GB2463530 A GB 2463530A GB 0817353 A GB0817353 A GB 0817353A GB 0817353 A GB0817353 A GB 0817353A GB 2463530 A GB2463530 A GB 2463530A
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- extract
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000000605 extraction Methods 0.000 title claims abstract description 37
- 235000008216 herbs Nutrition 0.000 title claims abstract description 7
- 239000002831 pharmacologic agent Substances 0.000 title 1
- 239000000284 extract Substances 0.000 claims abstract description 72
- 238000000034 method Methods 0.000 claims abstract description 42
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 239000002994 raw material Substances 0.000 claims abstract description 17
- 244000042664 Matricaria chamomilla Species 0.000 claims abstract description 16
- 244000126014 Valeriana officinalis Species 0.000 claims abstract description 14
- 235000013832 Valeriana officinalis Nutrition 0.000 claims abstract description 14
- 235000016788 valerian Nutrition 0.000 claims abstract description 14
- 235000004429 Matricaria chamomilla var recutita Nutrition 0.000 claims abstract description 11
- 235000006886 Zingiber officinale Nutrition 0.000 claims abstract description 11
- 238000009472 formulation Methods 0.000 claims abstract description 11
- 235000008397 ginger Nutrition 0.000 claims abstract description 11
- 244000178231 Rosmarinus officinalis Species 0.000 claims abstract description 9
- 239000001841 zingiber officinale Substances 0.000 claims abstract description 8
- 235000006693 Cassia laevigata Nutrition 0.000 claims abstract description 7
- 244000273928 Zingiber officinale Species 0.000 claims abstract description 7
- 229940124513 senna glycoside Drugs 0.000 claims abstract description 7
- 238000012377 drug delivery Methods 0.000 claims abstract description 6
- 235000007232 Matricaria chamomilla Nutrition 0.000 claims abstract description 5
- 230000001804 emulsifying effect Effects 0.000 claims abstract description 4
- 235000015639 rosmarinus officinalis Nutrition 0.000 claims abstract description 3
- 239000000470 constituent Substances 0.000 claims abstract 8
- 235000017945 Matricaria Nutrition 0.000 claims abstract 2
- 239000000401 methanolic extract Substances 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 13
- 229940088679 drug related substance Drugs 0.000 claims description 7
- 244000037364 Cinnamomum aromaticum Species 0.000 claims description 6
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 claims description 6
- 241000196324 Embryophyta Species 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 6
- DOUMFZQKYFQNTF-WUTVXBCWSA-N (R)-rosmarinic acid Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-WUTVXBCWSA-N 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 3
- 230000008020 evaporation Effects 0.000 claims description 3
- 229940102465 ginger root Drugs 0.000 claims description 3
- NLDDIKRKFXEWBK-AWEZNQCLSA-N gingerol Chemical compound CCCCC[C@H](O)CC(=O)CCC1=CC=C(O)C(OC)=C1 NLDDIKRKFXEWBK-AWEZNQCLSA-N 0.000 claims description 3
- JZLXEKNVCWMYHI-UHFFFAOYSA-N gingerol Natural products CCCCC(O)CC(=O)CCC1=CC=C(O)C(OC)=C1 JZLXEKNVCWMYHI-UHFFFAOYSA-N 0.000 claims description 3
- 238000001694 spray drying Methods 0.000 claims description 3
- FEBNTWHYQKGEIQ-SUKRRCERSA-N valerenic acid Chemical compound C[C@@H]1CC[C@@H](\C=C(/C)C(O)=O)C2=C(C)CC[C@H]12 FEBNTWHYQKGEIQ-SUKRRCERSA-N 0.000 claims description 3
- FUHPCDQQVWLRRY-UHFFFAOYSA-N valerenic acid Natural products CC1CCC(C=C(/C)C(=O)O)C2C1CC=C2C FUHPCDQQVWLRRY-UHFFFAOYSA-N 0.000 claims description 3
- OQWKEEOHDMUXEO-UHFFFAOYSA-N (6)-shogaol Natural products CCCCCC=CC(=O)CCC1=CC=C(O)C(OC)=C1 OQWKEEOHDMUXEO-UHFFFAOYSA-N 0.000 claims description 2
- ZZAFFYPNLYCDEP-HNNXBMFYSA-N Rosmarinsaeure Natural products OC(=O)[C@H](Cc1cccc(O)c1O)OC(=O)C=Cc2ccc(O)c(O)c2 ZZAFFYPNLYCDEP-HNNXBMFYSA-N 0.000 claims description 2
- OQWKEEOHDMUXEO-BQYQJAHWSA-N [6]-Shogaol Chemical compound CCCCC\C=C\C(=O)CCC1=CC=C(O)C(OC)=C1 OQWKEEOHDMUXEO-BQYQJAHWSA-N 0.000 claims description 2
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- DOUMFZQKYFQNTF-MRXNPFEDSA-N rosemarinic acid Natural products C([C@H](C(=O)O)OC(=O)C=CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-MRXNPFEDSA-N 0.000 claims description 2
- TVHVQJFBWRLYOD-UHFFFAOYSA-N rosmarinic acid Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=Cc2ccc(O)c(O)c2)C=O TVHVQJFBWRLYOD-UHFFFAOYSA-N 0.000 claims description 2
- 229940076742 senna leaves Drugs 0.000 claims description 2
- 229930186851 sennoside Natural products 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 12
- 241000894007 species Species 0.000 claims 7
- 230000001747 exhibiting effect Effects 0.000 claims 6
- 241000522641 Senna Species 0.000 claims 5
- 241000234314 Zingiber Species 0.000 claims 4
- 229940070641 chamomile flowers Drugs 0.000 claims 3
- 239000000126 substance Substances 0.000 claims 3
- 239000007791 liquid phase Substances 0.000 claims 2
- 239000002245 particle Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 238000003809 water extraction Methods 0.000 claims 2
- IPQVTOJGNYVQEO-UHFFFAOYSA-N 9-[2-carboxy-4-hydroxy-10-oxo-5-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9h-anthracen-9-yl]-4-hydroxy-10-oxo-5-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-9h-anthracene-2-carboxylic acid Chemical class OC1C(O)C(O)C(CO)OC1OC1=CC=CC2=C1C(=O)C1=C(O)C=C(C(O)=O)C=C1C2C1C2=CC(C(O)=O)=CC(O)=C2C(=O)C2=C(OC3C(C(O)C(O)C(CO)O3)O)C=CC=C21 IPQVTOJGNYVQEO-UHFFFAOYSA-N 0.000 claims 1
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 abstract description 3
- 239000004094 surface-active agent Substances 0.000 abstract description 2
- 241001249696 Senna alexandrina Species 0.000 abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 11
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- 238000003756 stirring Methods 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229920002125 Sokalan® Polymers 0.000 description 4
- 229930003935 flavonoid Natural products 0.000 description 4
- 235000017173 flavonoids Nutrition 0.000 description 4
- 150000002215 flavonoids Chemical class 0.000 description 4
- 150000008442 polyphenolic compounds Chemical class 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 229960001631 carbomer Drugs 0.000 description 3
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- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
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- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
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- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229930182482 anthraquinone glycoside Natural products 0.000 description 1
- -1 anthraquinone glycosides sennosides Chemical class 0.000 description 1
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- 239000002111 antiemetic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 1
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 description 1
- 229940117893 apigenin Drugs 0.000 description 1
- 235000008714 apigenin Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000002780 gingerol Nutrition 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002475 laxative effect Effects 0.000 description 1
- 229930013686 lignan Natural products 0.000 description 1
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- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 235000017807 phytochemicals Nutrition 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
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- 238000003860 storage Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/482—Cassia, e.g. golden shower tree
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/84—Valerianaceae (Valerian family), e.g. valerian
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A method for preparing an extract containing pharmacologically active constituents from certain traditionally used medicinal herbs comprises extracting the botanical raw material with subcritical water and then removing the water to give a pharmaceutically acceptable extract. The extraction may be conducted at 200-230°C and/or 70-85 bar. The medicinal herb may be Valerian officinalis, rosmarinus officinalis (rosemary), matricaria recuitita (german chamomile), zingiber officinale (ginger) or cassia angustifolia (senna). These sub-critical water extracts may be similar in composition to those extracts obtained by means of methanolic extraction. The extract may be formulated as a self emulsifying drug delivery system in order to improve the bioavailability of the active constituents: a formulation may comprise the extract, lauroyl macrogolglyceride and surfactant.
Description
I
A Method of Preparing Pharmacologically Active Extracts from Certain Medicinal Herbs in Traditional use in Europe Without the Use of an Organic Solvent.
FIELD OF THE iNVENTION.
This invention relates to a method of producing an extract from certain herbs, used traditionally in Europe for their medicinal value, without the use of an organic solvent.
BACKGROUND TO THE INVENTION.
Higher plants are unsurpassed in their ability to produce biologically active molecules often of great complexity. These plant "secondary metabolites" have proven a fruitful source of new pharmaceuticals. Often the first use of these compounds as been in the form of traditional herbal medicines. However the structure of the active compounds is frequently so complex that synthetic chemistry can provide no economically viable route to the molecule and this has to be isolated from the plant material.
Simple aqueous extraction of the biomass almost invariably results in a complex extract in which the target compound is diluted by a range of other unwanted phytochemicals derived from the plant, including proteins, sugars and other carbohydrates.
Extraction with a lower alcohol, typically ethanol or methanol, is traditionally a very popular means of obtaining a pharmacologically active preparation from a medicinal herb. The use of an alcohol has the advantage over an aqueous extraction that the highly polar compounds such as carbohydrates, sugars and proteins (which generally are inactive and serve only to add bulk and dilute the concentration of the active compounds) are not extracted.
However the obvious disadvantages of the use of an alcohol in extraction is that it is flammable, necessitating expensive precautions during processing, and also the recovery of the organic solvent for disposal or for further purification and re-use is required. Methanol in addition is highly toxic, and residual levels must be rigorously limited in a pharmaceutical preparation. Indeed due to this high toxicity of methanol, it is frequently substituted by a mixture of the more polar water and the less polar ethanol to produce an extraction solvent of comparable polarity.
A more recent approach that has also successfully applied is the production of a high potency extract, standardised on the content of the active substance, using extraction with a subcritical fluid or liquefied gas, most commonly carbon dioxide. One drawback of LCO2 extraction is that the technique is limited to less polar compounds.
It will not extract the compounds most readily soluble in methanol or aqueous alcohol mixtures, including the important class of flavonoids and other polyphenolic compounds such as lignans. The importance of polyphenolic compounds as potential new drugs is increasingly being recognised; with anti-inflammatoiy activity, anti-bacterial activity and a wide range of activities related to suppression of tumour growth (including inhibition of angiogenesis and reversal of multidrug resistance) being well established.
A more recent example of a high pressure liquefied gas which is being evaluated as an extraction agent and which promises capabilities not exhibited by LCO2 is high pressure superheated water at >150°C. Importantly, it is capable of solubilising more polar compounds than LCO2 extraction. Subcritical water has the unique property that the polarity changes in a well established and predictable manner as temperature is increased; thus at 150°C subcritical water has a polarity equivalent to a 50:50 mixture of water and alcohol under normal conditions, and the polarity further decreases to a value equivalent to methanol alone at 230°C. It is this property that is the basis of this invention: by employing subcritical water it is found that extracts equivalent in composition to those produced by methanol can be obtained without the disadvantages resulting from the use of a toxic and flammable solvent.
The traditionally used medicinal herbs for which extraction with subcritical water is described in this invention all produce an extract with methanol that has been widely reported in the literature to contain flavonoid or other phenolic compounds which produce important pharmacological effects as follows: The methanolic extract of Valerian officinalis root contains valerenic acid that is now established as the principal active substance responsible for the sedative and anxiolytic action of the traditionally used extracts.
The methanolic extract of Rosmarinus officinalis (rosemaiy) leaves contains high levels of rosmarinic acid and related compounds which are known to be largely responsible for the strong anti-inflammatory and anti-bacterial activity of the herb.
The methanolic extract of Matricaria recutita (German chamomile) flowers contains significant levels of apigenin and related flavonoids that are known to exhibit a range of anti-inflammatory actions.
The methanolic extract of Zingiber officinale (ginger) root contains significant levels of the gingerol and shogaol components known to be responsible for the anti-emetic and anti-inflammatory actions.
The methanolic extract of Cassia angutfolia (senna) leaves contains the anthraquinone glycosides sennosides A-D that are known to be responsible for the laxative action of the herb.
Thus as the subcritical water extract of the herbs as described in this invention are demonstrated to exhibit a composition essentially similar to that of the corresponding methanolic extract then it can be expected that these extracts will exhibit comparable pharmacological properties to these and to the compound contained therein.
A problem limiting the use of flavonoids and related polyphenolic compounds in therapeutic situations in which systemic treatment rather than local application is required is poor water solubility. This is largely responsible for the low circulating plasma levels after a single oral dose and results in the majority of the dose being excreted without absorption.
Hence this invention also describes self emulsifying formulations which increase the water solubility of these compounds, thus increasing their oral bioavailability and therapeutic efficacy.
SUMMARY OF THE INVENTION.
Example 1.
The extraction apparatus consists of: * Two suitable stainless steel vessels capable of resisting high temperature and pressure connected by stainless steel tubing, the first to act as a reservoir in which subcritical water is produced prior to introduction to the second extraction vessel. These are contained in a thermostatted oven.
* The first reservoir is connected via an inlet valve to a high pressure pump outside the thermostatted oven.
* The extraction vessel is also connected via an outlet valve to a stainless steel receiver vessel outside the thermostatted oven but maintained at approximately 90°C.
* A valve from the receiver vessel allows the solution that accumulates to be transferred to a suitable storage vessel.
A schematic representation of a suitable arrangement of the extraction apparatus is provided as Figure 1.
Coarsely ground valerian root botanical raw material is packed into the stainless steel extraction vessel. The extraction vessel is then filled with deionised water (equivalent to approximately four times the mass of botanical raw material employed) and the temperature and pressure of the extraction vessel gradually raised to respectively 230°C and 85 bar. The extraction vessel is then held at these conditions for up to 15 minutes before the resulting solution is forced from the vessel by passing a second quantity of subcritical water into the system to continue the extraction. In all four portions of subcritical water are used to extract the botanical raw material in the manner described above.
Alternatively the same extraction may be achieved in a dynamic mode by passing the same quantity of subcritical water maintained at 230°C and 85 bar through the botanical raw material packed in the extraction vessel over the course of approximately 1 hour.
The extract is isolated from the solution resulting from the extraction by removing the water by evaporation, the final stages of which are preferably carried out under reduced pressure.
Alternatively the extract may be isolated from the solution resulting from the extraction by removing the water by the process of either freeze drying or spray drying.
A TLC fingerprint representative of the extract (also termed a botanical drug substance) produced in this example is given in Figure 2.
Example 2.
A method as described in example I wherein the botanical raw material is ground rosemary leaves.
A TLC fingerprint representative of the extract produced in this example is given in Figure 3.
Example 3.
A method as described in example 1 wherein the botanical raw material is ground flowers of German chamomile.
A TLC fingerprint representative of the extract produced in this example is given in Figure 4.
Example 4.
A method as described in example 1 wherein the botanical raw material is ground ginger root.
A TLC fingerprint representative of the extract produced in this example is given in Figure 5,
Example 5.
A method as described in example I wherein the botanical raw material is ground senna leaves.
A TLC fingerprint representative of the extract produced in this example is given in Figure 6.
While the preferred embodiments of the invention have been described above, it will be recognised and understood that various modifications may be made therein, and the appended claims are intended to cover all such modifications which may fall within the spirit and scope of the invention.
Example 6.
A Self Emusifying Drug Delivery System (SEDDS) formulation for oral administration of the extracts containing the poorly water soluble polyphenols can be prepared as follows: Extract (selected from the extracts produced in Examples 1-5) 15% w/w Lauroyl macrogoiglycerides EP (e.g Gelucire 44/14) 65-85% w/w Surfacant (e.g Cremophor RH4O or Labrafac) 0-20% w/w The extract is dispersed with stirring in the molten lauroyl macrogolglycerides at 70- 80°C. The surfactant is then added and stirring continued for a further 5 minutes.
Using suitable automatic or manual equipment the molten mixture is then dispensed into two piece hard shell gel capsules that are then sealed.
Example 7a
A cream formulation for topical application of the extracts can be prepared as follows: Extract (selected from the extracts produced in Examples 2-3) 2% w/w Cetostearyl alcohol EP 7% w/w Macrogol cetostearyl ether (e.g Cremophor A61A25) 3% w/w Liquid paraffin EP 12% w/w Parabens (e.g. Nipastat) 0.2% w/w Deionised water 67.8% w/w Propylene Glycol EP 8% wlw The extract is dispersed in the propylene glycol at 70-80°C with stirring. All other ingredients except the water are mixed at 80°C and then added with stirring to the water that was heated separately to 80°C. The dispersion of extract in propylene glycol is then added to this mixture maintained at 70-80°C with stirring. The formulation is then filled into tubes.
Example 7b
A hydroalcoholic gel formulation for topical application of the extracts can be prepared as follows: Extract (selected from the extracts produced in Examples 2-3) 2% w/w Ethanol EP 44% w/w Carbomer (e.g. carbopol 980 NF) 3% w/w Deiomsed water 51% wlw Sodium hydroxide (aq) qs to neutralise The extract is dissolved in the ethanol at 50-60°C with stirring. The carbomer is then added slowly to the water with rapid stirring. The extract solution is then added to the aqueous carbomer whilst stirring. The resulting mixture is then neutralised by slowly adding aqueous sodium hydroxide to produce a smooth semi-solid.
The formulation is then filled into tubes.
Claims (9)
- CLAIMS1. A method of preparing an extract containing pharmacologically active constituents from certain traditionally used medicinal herbs comprising reduction of the particle size of the botanical raw material as appropriate, extracting the botanical raw material with subcritical water, and then removing the water from the resulting solution to produce a pharmaceutically acceptable extract.
- 2. The method according to claim 1-6 wherein the extraction is carried out at a temperature in the range 150-260°C, and most preferably in the range 200-230°C.
- 3. The method according to claim 1-6 wherein the extraction is carried out at a pressure in the range 15-100 bar sufficient to maintain the water in the liquid phase, and most preferably at 70-85 bar 4. The method according to claims 1-6 wherein the medicinal herb is selected from the group consisting of the traditionally used parts of Valerian officinalis, Rosmarinus officinalis (rosemary), Matricaria recuitita (german chamomile), Zingiber officinale and Cassia angustfolia (senna).5. The method according to claim 1-6 wherein the water is removed to yield the extract by evaporation.6. The method according to claim 1-6 wherein the water is removed to yield the extract by freeze drying or spray drying.7. The method according to any preceding claim wherein the extraction of valerian root, produces an extract with a TLC fingerprint substantially as illustrated in Figure 2, which is essentially similar to the corresponding methanolic extract and exhibiting a significant spot attributable to valerenic acid.8. The method according to any preceding claim wherein the extraction of rosemary leaves produces an extract with a TLC fingerprint substantially as illustrated in Figure 3, which is essentially similar to the corresponding methanolic extract and exhibiting a significant spot attributable to rosmarinic acid.9. The method according to any preceding claim wherein the extraction of German chamomile flowers produces an extract with a TLC fingerprint substantially as illustrated in Figure 4, which is essentially similar to the corresponding methanolic extract.10. The method according to any preceding claim wherein the extraction of ginger root produces an extract with a TLC fingerprint substantially as illustrated in Figure 5, which is essentially similar to the corresponding methanolic extract and exhibiting a significant spot attributable to 6-shogaol and to 6-gingerol.11. The method according to any preceding claim wherein the extraction of senna leaves produces an extract with a TLC fingerprint substantially as illustrated in Figure 6, which is essentially similar to the corresponding methanolic extract and exhibiting a significant spots attributable to respectively sennosides A,B,C, and D. * 7 12. The use of a botanical drug as claimed in any of the preceding claims that consist essentially of botanical drug substances.13. The use of a botanical drug as claimed in claim 12 further comprising excipients.14. The use of a botanical drug as claimed in claim 12 wherein the botanical drugs substances comprise total extracts derived from the botanical raw materials.15. The use of a botanical drug as claimed in claim 12 wherein the botanical drugs substances comprise more refined fractions derived from the total extracts of the botanical raw materials.16. The use of a botanical drug as claimed in claim 12 wherein the botanical drugs substances are standardised extracts..17. The method according to any preceding claim wherein the pharmacologically active extract is formulated in a self emulsifying drug delivery system to improve the oral bioavailability of the active constituents.18. The method according to claim 17 wherein the self emulsifying drug delivery system is based on the formulation described in Example 6.19. The method according to claims 17-18 wherein the pharmacologically active extract is selected from the list of the subcritical water extracts of valerian root, rosemary leaves, German chamomile flowers and ginger root.20. The method according to any preceding claim wherein the pharmacologically active extract is formulated in a topical vehicle formulated to increase bioavailability of the active constituents.21. The method according to claim 20 wherein the topical vehicle is based on the formulation described in Example 7.22. The method according to claim 20-21 wherein the pharmacologically active extract is the subcritical water extract of rosemary leaves or German chamomile flowers, either alone or in combination.* amended claims have been filed as follows:CLAIMS1. A method of preparing an extract containing pharmacologically active constituents from certain traditionally used medicinal plants, comprising reduction of the particle size of the raw material as appropriate, extracting the botanical raw material with sub-critical water, and then removing the water from the resulting solution to produce a pharmaceuticallyacceptable extract.2. The method according to claims 1-6 wherein the extraction is carried out at a temperature in the range 150-230°C, and most preferably in the range 200-230°C.3. The method according to claim 1-6 wherein the extraction is carried out at a pressure in the range 15-100 bar sufficient to maintain the water in the liquid phase, and most preferably at 70-8 5 bar.
- 4. The method according to claims 1-6 wherein the medicinal plant is selected from the group consisting of the traditionally used parts of Valeriana officinalis (valerian) Malricaria recutila (German chamomile), Zingi her officinale (ginger) and Cassia angustfo1ia (senna), and also including species closely related to any of the foregoing.
- 5. The method according to claims 1-6 wherein the water is removed to yield the extract by evaporation.
- 6. The method according to claims 1-6 wherein the water is removed to yield the extract by freeze diying or spray drying,
- 7. The method according to any preceding claim wherein the sub-critical water extraction of Valeriana officinalis (valerian) or a closely related species produces an extract with a mc fingerprint substantially as illustrated in Figure 2, which is essentially similar to the corresponding methanol extract and exhibits a significant spot due to valerenic acid.
- 8. The method according to any preceding claim wherein the sub-critical water extraction of Matricaria recutita (German chamomile) or a closely related species produces an extract with a TLC fmgerprint substantially as illustrated in Figure 3, which is essentially similar to the corresponding methanol extract.
- 9. The method according to any preceding claim wherein the sub-critical water ***. extraction of Zingi her officinale (ginger) or a closely related species produces an extract with * a TLC fingerprint substantially as illustrated in Figure 4, which is essentially similar to the * corresponding methanol extract and exhibiting significant spots due to 6-gingerol & 6-shoagaol.****.. * *10. The method according to any preceding claim wherein the sub-critical water * extraction of Cassia angustfo1ia (senna) or a closely related species produces an extract with a TLC fingerprint substantially as illustrated in Figure 5, which is essentially similar to the :. corresponding methanol extract and exhibiting significant spots attributable to respectively * setmosides A-D. ***S11. The use of a botanical drug substance as claimed in any of the preceding claims that consist essentially of botanical drug substances.12. The use of a botanical drug as claimed in claim 11 further comprising excipients.13. The use of a botanical drug as claimed in claim 11 wherein the botanical drug substances comprise total extracts derived from the botanical raw materials.14. The use of a botanical drug as claimed in claim 11 wherein the botanical drug substances compnse more refined fractions derived from the total extracts of the botanical raw materials.15. The use of a botanical drug as claimed in claim 11 wherein the botanical drug substances are standardised extracts.16. The method according to any preceding claim wherein the pharmacologically active extract is formulated in a self emulsif,'mg drug delivery system to improve the oral bioavailability of the active constituents.17. The method according to claim 16 wherein the self emulsif'ing drug delivery system is based on the formulation described in Example 5.18. The method according to claims 16-17 wherein the pharmacologically active extract as described in any preceding claim is selected from the list of subcritical water extracts of Valeriana officinalis (valerian) Matricaria recutita (German chamomile), Zingiber officinale (ginger) and Cassia angustfolia (senna), and also including species closely related to any of the foregoing.19. The method according to any preceding claim wherein the pharmacologically active extract is formulated in a topical vehicle formulated to increase efllcacy of the active constituents.20. The method according to claim 19 wherein the topical vehicle is based on the formulations described in Examples 6 & 7 21. The method according to claim 19-20 wherein the pharmacologically active extract as described in any preceding claim is selected from the list of subcritical water extracts of * Valeriana officinalis (valerian) Malricaria recutita (German chamomile), Zingiber officinale * (ginger) and Cassia angusqfolia (senna), and also including species closely related to any of *:: the foregoing.SSS* .5 * .S S..S S. * * * **. 5.S
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GB0817353.6A GB2463530B (en) | 2008-09-23 | 2008-09-23 | The sub-critical water extraction of German Chamomile flowers |
PCT/GB2009/002229 WO2010034971A2 (en) | 2008-09-23 | 2009-09-17 | Sub-critical water extraction of medicinal plants |
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GB2476070A (en) * | 2009-12-10 | 2011-06-15 | Kenneth Davison | Subcritical water extraction of Hawthorn Crategus monogyna, Pueraria lobata and Centella asiatica |
CN103163260A (en) * | 2011-12-16 | 2013-06-19 | 成都康弘制药有限公司 | Fingerprints of drugs and determination method thereof |
CN105866319A (en) * | 2016-04-20 | 2016-08-17 | 广西壮族自治区梧州食品药品检验所 | Method for qualitatively identifying baicalin in Qinghouliyan granules by thin-layer chromatography |
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Cited By (4)
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GB2476070A (en) * | 2009-12-10 | 2011-06-15 | Kenneth Davison | Subcritical water extraction of Hawthorn Crategus monogyna, Pueraria lobata and Centella asiatica |
CN103163260A (en) * | 2011-12-16 | 2013-06-19 | 成都康弘制药有限公司 | Fingerprints of drugs and determination method thereof |
CN103163260B (en) * | 2011-12-16 | 2014-12-24 | 成都康弘制药有限公司 | Determination method of fingerprints of drugs |
CN105866319A (en) * | 2016-04-20 | 2016-08-17 | 广西壮族自治区梧州食品药品检验所 | Method for qualitatively identifying baicalin in Qinghouliyan granules by thin-layer chromatography |
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GB0817353D0 (en) | 2008-10-29 |
GB2463530A9 (en) | 2010-04-21 |
GB2463530B (en) | 2012-08-08 |
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