WO2023236096A1 - 植物挥发油组合物及其制备方法 - Google Patents

植物挥发油组合物及其制备方法 Download PDF

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WO2023236096A1
WO2023236096A1 PCT/CN2022/097589 CN2022097589W WO2023236096A1 WO 2023236096 A1 WO2023236096 A1 WO 2023236096A1 CN 2022097589 W CN2022097589 W CN 2022097589W WO 2023236096 A1 WO2023236096 A1 WO 2023236096A1
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volatile oil
oil composition
plant volatile
plant
surfactant
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PCT/CN2022/097589
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English (en)
French (fr)
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李存诏
赖绪明
赖秉杉
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威海天原生物科技有限公司
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Priority to PCT/CN2022/097589 priority Critical patent/WO2023236096A1/zh
Publication of WO2023236096A1 publication Critical patent/WO2023236096A1/zh

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/01Hydrocarbons
    • A61K31/015Hydrocarbons carbocyclic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/075Ethers or acetals
    • A61K31/085Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/11Aldehydes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/54Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38Cellulose; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/06Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • A61P39/06Free radical scavengers or antioxidants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/61Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/82Theaceae (Tea family), e.g. camellia

Definitions

  • the present invention relates to plant volatile oils, and in particular to a plant volatile oil composition and a preparation method thereof.
  • Volatile oil also known as essential oil, is a liquid extracted from various parts of plants through steam distillation, pressing, solvent extraction, etc. It can provide diversified use effects depending on the source.
  • cinnamon oil is obtained from the bark of the cinnamon tree and contains more than 80% cinnamaldehyde (Cinnamaldehyde, also known as cinnamaldehyde). It is a yellow viscous liquid that can be used as a food spice, insecticide and antibacterial agent. etc., and has antioxidant, anti-inflammatory and uric acid-lowering effects; taking angelica oil as an example, it is taken from the roots of angelica and has the effects of nourishing and activating blood, beautifying skin color and improving hair loss.
  • volatile oils are mostly insoluble in water and easily soluble in organic solvents such as anhydrous ethanol, ether, chloroform, etc.
  • organic solvents are often used to aid dissolution. Therefore, organic solvents cannot be completely removed, and their application scope is limited. Conducive to preservation and other issues.
  • the conventional coating technology has problems such as complicated operation steps, poor stability, and affecting the antioxidant effect of volatile oils. There are shortcomings that need to be improved urgently.
  • the main purpose of the present invention is to provide a plant volatile oil composition and a preparation method thereof.
  • the plant volatile oil composition has good water solubility and antioxidant effect, and has the advantages of high economy, long storage period, etc., and can be used for large-scale, Reproducibly fabricated and demonstrated additional efficacy with high loading efficiency.
  • a highly stable plant volatile oil composition which can be used for partial or systemic release and absorption; it is stable before release and use, and avoids degradation, sourness, pH changes, etc. The qualitative change caused by this phenomenon; however, it can still be quickly released, penetrated, and absorbed during the release stage of the main ingredients.
  • the plant volatile oil composition can be a liquid, semi-solid or solid composition; the semi-solid or solid composition is preferred, and the solid composition is most preferred.
  • the use or preparation of the plant volatile oil composition avoids the conventional interaction of excipients after adding excipients, reduces unpleasant taste or smell, and ensures the release efficiency and efficiency of various application forms.
  • the release rate can be used in various types of products.
  • the present invention provides a plant volatile oil composition, including: at least one main particle, each of the main particles includes a core layer and at least one protective layer, the core layer includes at least one plant volatile oil, and the at least one The protective layer covers the core layer and includes at least one phospholipid material and at least one surfactant; and a carrier, in which the at least one main particle is dispersed.
  • Each of the main particles is a nanoparticle, and the particle size of each of the main particles is preferably 30-500 nanometers, and most preferably no larger than 150 nanometers.
  • a highly stable plant volatile oil composition which may contain one or more volatile oils separated from plants.
  • the components of the plant volatile oil may include, but are not limited to, at least one of cinnamaldehyde, eugenol, ligustilide and terpinen-4-ol.
  • the vegetable oils selected in the present invention include, but are not limited to, at least one of cinnamon essential oil, clove oil, angelica oil and tea tree essential oil.
  • the weight percentage of the plant volatile oil in the solidified plant volatile oil composition is in the range of about 1% to about 35%, preferably in the range of about 10% to about 32%, and more preferably in the range of about 14% to about 14%. In the range of about 31%.
  • the vegetable oil composition contains a lipid that is solid at room temperature, preferably a lipid that is solid at 35°C, and more preferably only uses a single lipid that is solid at 35°C. .
  • the single lipid is preferably a phospholipid material.
  • the phospholipid can be a natural phospholipid, such as soybean lecithin, egg lecithin, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidic acid, sphingomyelin, bisphosphatidic acid phospholipid, etc.; it can also be a synthetic phospholipid, such as: Dipalmitoylphosphatidylcholine, dimyristoylphosphatidylglycerol, distearoylphosphatidylglycerol, distearoylphosphatidylcholine and egg phosphatidylcholine, etc., as well as hydrogenated or partially hydrogenated lecithin and phospholipids .
  • the phospholipid may also be a saturated or unsaturated phospholipid.
  • the present invention is a plant volatile oil composition, which contains one or more surfactants, preferably only one surfactant.
  • the surfactant can be a cationic surfactant, anionic surfactant, zwitterionic surfactant or nonionic surfactant. Among them, nonionic surfactants are preferred.
  • Optional surfactants for use in the present invention exhibit HLB values in the range of about 12 to about 17. It is known in the art that the HLB value is used to classify surfactants based on the balance between their hydrophilic and lipophilic parts. A surfactant with a higher HLB value is more hydrophilic and a lower HLB value is hydrophilic. The worse the sex. A single surfactant having an HLB value ranging from about 12 to about 17 may be used in the present invention, or a combination of high HLB surfactants and low HLB surfactants may be used; such mixed surfactants are A certain proportion is present such that the mixture of surfactants remains exhibiting a final HLB value of about 12 to about 17.
  • the surfactant includes but is not limited to water-soluble vitamin E, polyethylene glycol, polysorbate, poloxamer, oleyl polyoxyglyceride, linoleyl polyoxyglyceride, and hydrogenated castor oil.
  • the plant volatile oil composition of the present invention uses polysorbitol esters as the surfactant system.
  • the surfactant accounts for about 2% to about 30% by weight of the plant volatile oil composition; preferably, it is about 2% to about 18%.
  • the plant volatile oil composition of the present invention is a dry solid composition.
  • the moisture content of the plant volatile oil composition does not exceed about 6%, and preferably does not exceed about 3%.
  • the plant volatile oil composition can be dried by methods such as spray drying, freeze drying, drum dryer drying, etc., and the freeze drying method is preferred.
  • the vegetable volatile oil composition of the present invention may further optionally contain one or more physiologically acceptable flavors.
  • the flavors may include natural flavoring agents, artificial flavoring agents or combinations thereof.
  • the optional flavors may be selected according to the corresponding A selection of volatile oils from this plant.
  • the plant volatile oil composition of the present invention further optionally contains one or more physiologically acceptable taste-masking agents.
  • the taste-masking agent may include, but is not limited to, sucralose, sucrose, saccharin or its salts, fructose, dextrose, corn syrup, aspartame, acesulfame potassium, xylitol, sorbitol, erythritol , ammonium glycyrrhizinate, thaumatin, neotame, mannitol, menthol, eucalyptus oil camphor, etc.
  • the invention provides a plant volatile oil composition that does not contain preservatives and antioxidants and can still maintain the effect of maintaining a stable composition for a long time.
  • the present invention can be enhanced by adding preservatives, antioxidants for the purpose of prolonging stability. Those of ordinary skill in the art will understand that further adding antioxidants to the composition to achieve a longer shelf life does not violate the present invention.
  • the invention provides a composition for improving the bioavailability of plant volatile oils. Furthermore, the present invention provides a composition that can more effectively exert the functions of plant volatile oils than the prior art. Or, in terms of use, compared with non-composition plant volatile oils or non-compositions of plant volatile oils of the present invention, to achieve the same effect, the plant volatile oil composition of the present invention requires a lower content of plant volatile oils. In addition, the plant volatile oil composition of the present invention can more conveniently and accurately calculate the content or actual usage amount, and can accurately measure and carry out standardized preparation whether used alone, added, or in combination with other ingredients.
  • the present invention can also use biologically acceptable pH adjusters to further adjust the plant volatile oil composition to the required pH value.
  • the pH adjusters include but are not limited to hydrochloric acid and/or sodium hydroxide.
  • buffer combinations including, but not limited to, citric acid/sodium bisulfate borate buffer, citric acid/citrate buffer, phosphates such as disodium or monosodium phosphate, sodium orthophosphate or phosphoric acid Disodium hydrogen, tromethamine or equivalent buffers are added to the plant volatile oil composition to adjust the pH value.
  • the plant volatile oil composition is a viscous colloid before drying and solidification, and has a viscosity ranging from 2,000 cps to 100,000 cps, preferably from 5,000 cps to 50,000 cps.
  • the present invention is a plant volatile oil composition, which further contains any suitable non-toxic carrier known in the art, which can be single or in combination.
  • the ratio of the carrier to the plant volatile oil can be selected from a ratio range of 1 to 5:1, preferably a ratio range of 3:1.
  • the carrier may include cyclodextrin, maltodextrin, cellulose, hydrogel, silicone hydrogel, starch, lactose, sucrose, sorbitol, silicon dioxide, talc, stearic acid, dicalcium phosphate, etc. or combinations thereof .
  • a carrier with a smaller content relative to the overall weight of the plant volatile oil composition is used; preferably a carrier that is not easily soluble in an aqueous environment; and preferably a carrier that is mixed with the at least one main particle to reach a dynamic equilibrium state. , a carrier that can still adsorb or wrap the at least one main particle, so that the at least one main particle will not break away from the carrier in the equilibrium state.
  • the content of the carrier accounts for the weight percentage of the plant volatile oil composition in the range of about 15% to about 70%, preferably in the range of about 35% to about 60%, More preferably, it is in the range of about 40% to about 55%.
  • the present invention also provides a method for preparing a plant volatile oil composition as described above, which includes the following steps: (1) mixing the at least one phospholipid material in an aqueous solution to form a dispersion solution; (2) mixing the At least one plant volatile oil is placed in the dispersion solution, so that the at least one phospholipid material coats the at least one plant volatile oil to form at least one intermediate particle; (3) Add the at least one surfactant to attach to the at least one intermediate particle , forming the at least one main particle; and (4) adding the carrier and dispersing the at least one main particle in the carrier.
  • Figure 1 is a perspective view of a preferred embodiment of the present invention.
  • Figure 2 is a schematic diagram of a manufacturing process according to a preferred embodiment of the present invention.
  • Figure 3 is a process block diagram of a preferred embodiment of the present invention.
  • Figure 4 is a bar chart of the effect on uric acid levels in rats according to a preferred embodiment of the present invention.
  • a plant volatile oil composition according to one embodiment of the present invention includes: at least one main particle 10 and a carrier 20 .
  • the plant volatile oil composition can be in liquid state, semi-solid state or dried into solid state.
  • Each main particle 10 includes a core layer 11 and at least one protective layer.
  • the core layer 11 includes at least one vegetable volatile oil.
  • the at least one protective layer covers the core layer 11 and includes at least one phospholipid material 12 and at least one interface active material. Agent 13; the at least one main particle 10 is dispersed in the carrier 20.
  • the at least one protective layer includes a first protective layer 121 and a second protective layer 131.
  • the at least one phospholipid material 12 is distributed on the outer surface of the core layer 11 and forms the first protective layer 121.
  • the at least one interface active layer The agent 13 is distributed on the outer surface of the first protective layer 121 and forms the second protective layer 131, so that the plant volatile oil is stably dispersed in the carrier 20 and is not easily aggregated to cause phase separation.
  • the effective average particle size of the at least one main particle 10 is no more than 150 nanometers, preferably between 40 nanometers and 120 nanometers.
  • the effective average particle size refers to that at least about 50% of the plurality of main particles 10 have the effective average particle size when measured using a dynamic light scattering instrument (DLS) or other methods.
  • DLS dynamic light scattering instrument
  • the weight ratio of the at least one phospholipid material 12 and the at least one surfactant 13 is between 1:3 and 1:6, so that the at least one surfactant 13 can be attached. outside the first protective layer 121 .
  • the at least one phospholipid material 12 includes synthetic or non-synthetic phospholipid material 12 .
  • the at least one phospholipid material 12 includes synthetic or non-synthetic phospholipids.
  • the phospholipids can be natural phospholipids, such as soybean lecithin, egg lecithin, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidic acid, and sphingomyelin.
  • the phospholipids can also be saturated or unsaturated phospholipids.
  • the weight ratio of the at least one phospholipid material 12 and the at least one surfactant 13 can also be between 3:1 and 6:1, and can be selected according to the properties of the at least one vegetable volatile oil.
  • the first protective layer 121 may be composed of the at least one phospholipid material 12 and the at least one surfactant 13 .
  • the at least one surfactant 13 accounts for about 2% to about 30% by weight of the plant volatile oil composition, preferably about 2% to about 18%, so as to provide a good coating effect.
  • the at least one surfactant 13 may include one or more surfactants 13 (preferably only one type is selected).
  • the at least one surfactant 13 may be a cationic surfactant, an anionic surfactant, or a zwitterionic surfactant. agent or nonionic surfactant.
  • the HLB value of the at least one surfactant 13 is preferably 12 to 17. A single surfactant with an HLB between 12 and 17 can be used, or a high HLB surfactant and a low HLB surfactant can be used. Mixed in specific proportions.
  • the at least one surfactant 13 is, for example, but not limited to, water-soluble vitamin E, polyethylene glycol, polysorbate, poloxamer, oleyl polyoxyglyceride, linoleyl polyoxyglyceride.
  • Glycerides hydrogenated castor oil polyoxyethylene, capryloyl caproyl polyoxyglyceride, polyoxyethylene castor oil derivatives, polyoxyethylene alkyl ethers, fatty acid sorbose esters, glyceryl monooleate, glyceryl monolinoleate , medium chain triglyceride, polyglyceryl oleate, lauryl polyoxyglyceride, stearyl polyoxyglyceride, propylene glycol dioctyl caprate, propylene glycol laurate, propylene glycol One of alcohol monolaurate, propylene glycol octanoate, propylene glycol monocaprylate, etc. or a combination thereof.
  • polysorbate is selected as the surfactant system.
  • the carrier 20 can be in various forms such as liquid, semi-solid, solid, granular, etc.; in the dried and solidified plant volatile oil composition, the content of the carrier 20 accounts for the weight percentage of the plant volatile oil composition: In the range of about 15% to about 70%, preferably in the range of about 35% to about 60%, more preferably in the range of about 40% to about 55%.
  • the carrier 20 includes cyclodextrin, maltodextrin, starch, silicon dioxide, cellulose, hydrogel, silicone hydrogel, lactose, sucrose, sorbitol, silicon dioxide, and talc. At least one of , stearic acid and dicalcium phosphate can be selected according to needs.
  • the carrier 20 can, for example, be in the form of granules and can be uniformly mixed with the plurality of main particles 10.
  • the carrier 20 is not easily soluble in an aqueous environment to facilitate the attachment of the plurality of main particles 10 thereto.
  • the plant volatile oil composition is composed of the following weight percentage components: the at least one surfactant 12% to 18%, the at least one phospholipid material 2% to 8% , the at least one plant volatile oil 5% to 15%, the carrier 15% to 25%, and the rest is water.
  • the at least one surfactant 13 includes Tween series surfactants
  • the at least one phospholipid material 12 includes lecithin
  • the at least one plant volatile oil includes cinnamon essential oil
  • the carrier 20 includes silicon dioxide.
  • the solubility of the plant volatile oil composition in water of the present invention is not less than 5000 ppm, and it is easy to use and has a wide range of applications; the DPPH free radical scavenging rate of the plant volatile oil composition is not less than 20%, and the antioxidant effect is better than that of uncoated The volatile oil of this plant has good results.
  • the plant volatile oil composition is composed of the following weight percentage components: the at least one surfactant 2% to 8%, the at least one phospholipid material 12% to 18% , the at least one plant volatile oil 5% to 15%, the carrier 15% to 25%, and the rest is water.
  • the at least one surfactant 13 includes Tween series surfactants
  • the at least one phospholipid material 12 includes lecithin
  • the at least one plant volatile oil includes angelica oil
  • the carrier 20 includes silicon dioxide, which can also provide good Covering effect.
  • the plant volatile oil composition may optionally further include one or more physiologically acceptable flavors, such as but not limited to natural flavoring agents, artificial flavoring agents or combinations thereof.
  • the optional flavor may be selected according to the corresponding Choose the plant volatile oil to have a better use experience.
  • the plant volatile oil composition may also optionally contain one or more physiologically acceptable taste-masking agents.
  • the taste-masking agents may be, for example, but not limited to, sucralose, sucrose, saccharin or its salts, fructose, dextrose, Sugar, corn syrup, aspartame, acesulfame potassium, xylitol, sorbitol, erythritol, ammonium glycyrrhizinate, thaumatin, neotame, mannitol, menthol, eucalyptus oil camphor, etc., It is used to cover up the original odor of other materials to improve user acceptance.
  • the plant volatile oil composition may further include one or more physiologically acceptable preservatives, antioxidants or glidants to achieve a longer shelf life.
  • the plant volatile oil composition may also include a biologically acceptable pH adjuster to further adjust the plant volatile oil composition to the required pH value.
  • the pH adjuster includes but is not limited to hydrochloric acid and/or sodium hydroxide, and may also Is a buffer combination component, which includes, but is not limited to, citric acid/sodium hydrogen sulfate borate buffer, citric acid/citrate buffer, phosphates such as disodium phosphate or monosodium phosphate, sodium hydrogen orthophosphate or dihydrogen phosphate. Sodium, tromethamine or equivalent buffer, etc.
  • the present invention also provides a method for preparing the plant volatile oil composition as described above, which includes the following steps:
  • Step (1) Mix the at least one phospholipid material 12 in an aqueous solution to form a dispersion solution.
  • the weight ratio of the at least one phospholipid material 12 to the aqueous solution is between 1:3 and 1:20, preferably between 1:14 and 1:18, and another preferably between 1:3 to 1:5, which can be selected according to the nature of the raw material to provide sufficient at least one phospholipid material 12 to facilitate subsequent coating of the plant volatile oil.
  • Step (2) Mix the at least one vegetable volatile oil in the dispersion solution so that the at least one phospholipid material 12 coats the at least one vegetable volatile oil to form at least one intermediate particle 10a.
  • the weight ratio of the at least one vegetable volatile oil to the aqueous solution is between 1:4 and 1:12, preferably between 1:8 and 1:10.
  • the stirring time of step (2) is not less than 20 minutes, whereby the plant volatile oil can be evenly dispersed into a plurality of oil droplets in the dispersion solution, and the at least one phospholipid material 12 can pass through its lipophilic end and hydrophilic end. The property differences are attached to the outer surfaces of the oil droplets to form the intermediate particles 10a.
  • step (1) to this step (4) the rotation speed is maintained at 100 rpm to 300 rpm for stirring and mixing to ensure that the vegetable volatile oil, the at least one intermediate particle 10a and the at least one main particle 10 are evenly dispersed and mixed with the at least one A phospholipid material 12 and the at least one surfactant 13 are mixed and contacted.
  • step (1) is performed at a temperature of 70°C to 90°C to hydrate and disperse the at least one phospholipid material 12 in the aqueous solution 30; step (2) to step (4) ) is carried out at a temperature below 50°C to prevent the formed particles from thermal disintegration.
  • the preparation method of the plant volatile oil composition of the present invention can be completed through a one-pot operation.
  • the raw materials are relatively simple and the operation is simple.
  • the steps are simple and there is no need to add additional organic solvents, which can effectively improve production efficiency and reduce solvent residues.
  • the at least one phospholipid material 12 is lecithin; the at least one plant volatile oil is cinnamon essential oil; and the at least one surfactant is selected. 13 is made of Tween 80; the carrier 20 is made of silica, and its commercial models can be Syloid XDP 3050, Syloid XDP 3150 or Syloid 244 FP.
  • 10 g of lecithin is first added to 160 ml of water (i.e., the aqueous phase solution 30) and stirred at 80° C. at a speed of 150 rpm for about 30 minutes, and then the heat source is removed.
  • the ratio of the at least one phospholipid material 12 to the at least one surfactant 13 is approximately 1:4; the ratio of the at least one phospholipid material 12 to the aqueous solution 30 is 1:16; The ratio of at least one plant volatile oil to the aqueous solution 30 is about 1:9.
  • step (5) is further included after step (4): drying and removing the aqueous solution 30 (such as freeze drying, spray drying, drum dryer drying and other drying methods) to obtain solidified
  • the plant volatile oil composition facilitates storage.
  • the moisture content of the plant volatile oil composition is not higher than 6% (preferably not higher than 3%) to facilitate preservation.
  • Comparative Example 1 is made with lecithin and cinnamon essential oil in equal proportions as in Example 1 without adding the at least one surfactant 13 and the carrier 20; Comparative Example 2 is made with equal proportions of lecithin and cinnamon essential oil as in Example 1.
  • Tween 80 and cinnamon essential oil are made without adding the at least one phospholipid material 12 and the carrier 20; Comparative Example 3 uses silicon dioxide and cinnamon essential oil in the same proportion as in Example 1, without adding the at least one phospholipid material 12 and the carrier 20. It is made under the conditions of a phospholipid material 12 and the at least one surfactant 13;
  • Comparative Example 4 is a control group without adding cinnamon essential oil in Example 1; Comparative Example 5 is pure cinnamon essential oil.
  • the component weight composition ratios of each embodiment and comparative example are listed in the following table:
  • Example 1 and Comparative Examples 1 to 5 are listed in the table below, where the "water solubility improvement rate” is calculated by multiplying the ratio of the water solubility of each Example or Comparative Example and cinnamon essential oil (i.e. Comparative Example 5) by 100%. "Antioxidant capacity improvement rate” is obtained by calculating the ratio of the DPPH clearance rate of each example or comparative example to the DPPH clearance rate of Comparative Example 5 multiplied by 100%. It should be noted that each of the examples and comparative examples was tested for water solubility after drying and solidification in step (5).
  • Example 1 the plant volatile oil composition
  • the first protective layer 121 and the second protective layer 131 formed by the at least one phospholipid material 12 and the at least one surfactant 13 can It effectively improves the water solubility of the plant volatile oil (the improvement rate is 389%), has good stability and is easy to match with different types of the carrier 20, and has a wide range of applications.
  • the antioxidant capacity of this plant volatile oil composition is increased by 959.3%, and the use effect is good.
  • Comparative Examples 1, 2 and 3 it can be seen from Comparative Examples 1, 2 and 3 that the at least one phospholipid material 12 and the at least one surfactant 13 are helpful in improving the water solubility of the plant volatile oil, and the at least one surfactant 13 and cinnamon essential oil have a better The good compatibility greatly improves its water solubility; however, the antioxidant capacity of Comparative Example 2 is lower than that of Comparative Example 5.
  • the at least one phospholipid material 12 and the at least one surfactant 13 can form a carrier 20 with a particle size of about 45 nanometers to 55 nanometers in water. Coating the at least one plant volatile oil has good stability and dispersion, and also helps to improve bioavailability.
  • step (6) can be further included: refining the solidified vegetable volatile oil composition to a mesh size of 40 to 80; for example but not limited to using a crusher or a vibrating screen. It can be refined to facilitate storage and subsequent application (for example, as a tablet, added to an emulsion, etc.), and it can also be refined into other sizes as needed.
  • Example 1 In order to further explore the protective effect of the first protective layer 121, the second protective layer 131 and the carrier 20 on the plant volatile oil, the aforementioned Example 1, Comparative Examples 1-3 and Comparative Example 5 were respectively tested at 25°C and Store at 60°C for 48 hours. The results are listed in the table below.
  • the antioxidant capacity retention rate is based on each example or control example (DPPH clearance rate stored at 60°C/DPPH clearance rate stored at 25°C). ⁇ 100. It can be clearly seen from the figure that in Example 1 under a high temperature environment of 60°C, through the first protective layer 121, the second protective layer 131 and the carrier 20, the plant volatile oil composition is stored at room temperature compared to group, the antioxidant capacity retention rate only decreased by about 12%.
  • the formed main particles 10 can effectively protect the active ingredients of the plant volatile oil and have good thermal stability. Compared with Comparative Example 5, Comparative Examples 1-3 can also provide a partial protective effect to avoid the decrease in the antioxidant capacity of cinnamon essential oil. Through the above experiments, it can be expected that the plant volatile oil composition has the advantages of good thermal stability and easy storage.
  • FIG 4 is an animal experiment based on the aforementioned Example 1 to evaluate its uric acid-lowering effect.
  • Wistar male rats weighing between 150 and 180 grams were selected and divided into control group, positive control group, control group and experimental group. The number of animals in each group was no less than 3.
  • 250 mg/kg BW/d Potassium Oxonate is administered by tube feeding to induce hyperuricemia, and then the corresponding medicine is administered by tube feeding one hour later.
  • the medicine in the control group is 0.5% sodium carboxymethylcellulose (CMC) aqueous solution
  • the medicine in the positive control group is 10 mg/kg Allopurinol (dispersed in 0.5% CMC aqueous solution)
  • the control group is 75 mg/kg Cinnamaldehyde (dispersed in 0.5% CMC aqueous solution)
  • the experimental group was 7.5 mg/kg of the plant volatile oil composition of Example 1 (dispersed in 0.5% CMC aqueous solution).
  • One hour after dosing blood was collected and the uric acid content in the blood was analyzed.
  • the uric acid content ratio in Figure 4 is the ratio of the uric acid content in the blood after administration to the uric acid content in the blood before induction, to determine the uric acid-lowering ability of each group. It can be seen from the control group and positive control group in the figure that the high uric acid induction method in this experiment can indeed increase the uric acid content in the animal's blood, and its uric acid content can be reduced after the administration of therapeutic drugs; in addition, it can be seen from the control group that 75mg Cinnamaldehyde/kg can reduce the uric acid content in animal blood. Compared with cinnamaldehyde, the plant volatile oil composition of Example 1 only needs to use 1/10 of the dosage of the control group to achieve similar effects and has a good uric acid-lowering effect. .
  • angelica oil is selected as the at least one vegetable volatile oil.
  • the types of the at least one phospholipid material 12, the at least one surfactant 13, the aqueous solution 30 and the carrier 20 are consistent with the aforementioned implementation.
  • the weight percentages are: angelica oil 6.4%, lecithin 14.3%, Tween 803.6%, silicon dioxide 18.6%, water 57.1%.
  • the plurality of main particles 10 with a particle size of about 145 nanometers can be produced through the above preparation method, and can also effectively coat angelica oil.

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Abstract

本发明关于一种植物挥发油组合物,包括:至少一主颗粒,各该主颗粒包括一核层及至少一保护层,该核层包括至少一植物挥发油,该至少一保护层包覆该核层且包括至少一磷脂类材料及至少一界面活性剂;及一载体,该至少一主颗粒分散于该载体中。本发明另提供一种植物挥发油组合物的制备方法,包括下列步骤:(1)混合该至少一磷脂类材料于一水相溶液中,形成一分散溶液;(2)混合该至少一植物挥发油于该分散溶液中,使该至少一磷脂类材料包覆该至少一植物挥发油,形成至少一中间颗粒;(3)加入该至少一界面活性剂以附接于该至少一中间颗粒,形成该至少一主颗粒;及(4)加入该载体并使该至少一主颗粒分散于该载体中。本发明具有良好的水溶性及抗氧化效果。

Description

植物挥发油组合物及其制备方法 技术领域
本发明与植物挥发油有关,特别是有关于一种植物挥发油组合物及其制备方法。
背景技术
挥发油又称为精油,一般自植物的各部位以蒸气蒸馏、压榨、溶剂提去等方式萃取而得的液体,依据来源不同而可提供多样化的使用效果。举例来说,肉桂油取自肉桂树皮,其含有80%以上的肉桂醛(Cinnamaldehyde,又称为桂皮醛),其为一种黄色黏稠状液体,可作为食用香料、除虫剂及抗菌剂等,且具有抗氧化、抗发炎及降尿酸等功效;又以当归油为例,其取自当归根部,具有补血活血、美化肤色及改善落发等功效。
习知的挥发油多难溶于水,易溶于无水乙醇、乙醚、氯仿等有机溶剂中,于加工制造时多需使用有机溶剂助溶,因而存在有机溶剂无法完全去除、应用范围有限、不利于保存等问题。此外,习知的包覆技术存在操作步骤繁复、稳定性不佳、影响挥发油的抗氧化效果等问题,存在亟待改善的缺弊。
因此,有必要提供一种新颖且具有进步性的植物挥发油组合物及其制备方法,以解决上述问题。
发明内容
本发明的主要目的在于提供一种植物挥发油组合物及其制备方法,该植物挥发油组合物具有良好的水溶性及抗氧化效果,且具有高经济性、储存期限长等优势,可进行大规模、重复性的制造,并显示出具有高载量效率的额外功效。
在本发明其中一个方面,是提供一种高稳定性的植物挥发油组合物,其可作为部分或全身性释放吸收使用;其在释放使用前是稳定的,避免了降解、酸味、pH值变化等所造成的质变现象;而在主成分释放阶段仍能快速进行释放、渗透、被吸收。该植物挥发油组合物可为液态、半固态或固态组合物;其中优选为半固态或固态组合物,最优选为固态组合物。该植物挥发油组合物在使用或制备上,避免了习知添加赋形剂后 会产生赋形剂交互作用,降低了令人不悦的口味或气味,并保障了各种施用形式的释放效率及释放率,可利用在各种不同型态的产品上。
在本发明其中一个方面,本发明提供一种植物挥发油组合物,包括:至少一主颗粒,各该主颗粒包括一核层及至少一保护层,该核层包括至少一植物挥发油,该至少一保护层包覆该核层且包括至少一磷脂类材料及至少一界面活性剂;及一载体,该至少一主颗粒分散于该载体中。各该主颗粒为奈米颗粒,各该主颗粒的粒径优选为30-500奈米,最优选为不大于150奈米。
在本发明其中一个方面,是提供一种高稳定性的植物挥发油组合物,其可包含一或多种从植物中分离出的挥发油。该植物挥发油的成分可包括但不限于肉桂醛、丁香油酚、藁本内酯及萜品烯-4-醇至少其中一者。本发明的所选用的植物油包括但不限于肉桂精油、丁香油、当归油及茶树精油至少其中一者。该植物挥发油占固体化的该植物挥发油组合物中的重量百分比为约1%至约35%的范围内,优选为占约10%至约32%的范围内,更优选为占约14%至约31%的范围内。
在本发明的一个方面,该植物油组合物含有在室温下呈现固体的脂质,优选为在35℃下呈现固体的脂质,更优选为仅使用一种在35℃下呈现固体的单一脂质。该单一脂质优选为一磷脂类材料。该磷脂可为天然磷脂,例如:大豆卵磷脂、鸡蛋卵磷脂、磷脂酰甘油、磷脂酰肌醇、磷脂酰乙醇胺、磷脂酸、鞘磷脂、双磷脂酸磷脂等;亦可为合成磷脂,例如:二棕榈酰磷脂酰胆碱、二肉荳蔻酰磷脂酰甘油、二硬脂酰磷脂酰甘油、二硬脂酰磷脂酰胆碱及卵磷脂酰胆碱等,以及氢化或部分氢化的卵磷脂和磷脂。该磷脂亦可以是饱和的或不饱和的磷脂。
本发明是一种植物挥发油组合物,其含有一或多种界面活性剂,优选仅含有一种界面活性剂。该界面活性剂可为阳离子界面活性剂、阴离子界面活性剂、两性离子界面活性剂或非离子性界面活性剂。其中优选为非离子性界面活性剂。
本发明可选用的界面活性剂表现出范围为约12至约17的HLB值。本领域中已知HLB值用于根据界面活性剂的亲水部分和亲油部分之间的平衡对界面活性剂进行分级,界面活性剂的HLB值越高越亲水,HLB值越低则亲水性越差。在本发明中可以使用一种具有范围从约12至约 17的HLB值的单一界面活性剂,亦可以使用高HLB界面活性剂和低HLB界面活性剂的组合;此类混合的界面活性剂以一定比例存在,使得界面活性剂的混合物保持显示出约12至约17的最终HLB值。该界面活性剂包括但不局限于水溶性维生素E类、聚乙二醇、聚山梨糖醇酯、泊洛沙姆、油酰聚氧甘油酯、亚油酯酰聚氧甘油酯、氢化蓖麻油聚氧乙烯、辛酰己酰聚氧甘油酯、聚氧乙烯蓖麻油衍生物、聚氧乙烯烷醚、脂肪酸山梨糖酯、单油酸甘油酯、单亚油酸甘油酯、中链三酸甘油脂、聚油酸甘油酯、月桂基聚氧甘油酯、硬脂酰基聚氧甘油酯、丙烯乙二醇癸酸二辛酯、丙烯乙二醇月桂酸酯、丙烯乙二醇单月桂酸酯、丙烯乙二醇辛酸酯、及丙烯乙二醇单辛酸酯等中之一或其组合。最优选为本发明的该植物挥发油组合物选用聚山梨糖醇酯类作为界面活性剂系统。在一特定具体实施例中,该界面活性剂占该植物挥发油组合物的重量百分比约2%至约30%;优选为约2%至约18%。
本发明的植物挥发油组合物为一干燥的固体组合物。该植物挥发油组合物的含水量不超过约6%,更佳者不超过约3%。该植物挥发油组合物可采用喷雾干燥、冷冻干燥、鼓式干燥机干燥等方法进行干燥,优选为冷冻干燥法。
本发明的植物挥发油组合物更进一步可选择性地含有一种或多种生理上可接受的风味剂,该风味剂可包括天然调味剂、人造调味剂或其组合,可选择的风味可以依据相应的该植物挥发油选择。
本发明的植物挥发油组合物更进一步可选择地含有一种或多种生理上可接受的掩味剂。该掩味剂可包括但不限于三氯蔗糖、蔗糖、糖精或其盐、果糖、右旋糖、玉米糖浆、阿斯巴甜、安赛蜜、木糖醇、山梨糖醇、赤藓糖醇、甘草酸铵、索马甜、纽甜、甘露糖醇、薄荷醇、桉树油樟脑等。
本发明提供了一种不含防腐剂、抗氧化剂的植物挥发油组合物,仍能保持长时间维持稳定性组合物态样的功效。然而,出于延长稳定性的目的,本发明可以通过添加防腐剂、抗氧化剂来加强。本领域的通常知识者应当能理解,进一步将组合物添加抗氧化剂,以达到更长的保存期限,并不会与本发明相违背。
本发明提供了一种提高植物挥发油的生物可利用度的组合物。更者, 本发明提供了一种相较于先前技术具有更有效发挥植物挥发油该有的使用功效的组合物。或者,在使用上,相较于非组合物的植物挥发油或非本发明的植物挥发油组合物,在发挥相同功效上,本发明的植物挥发油组合物所需使用的植物挥发油含量更低。又,本发明的植物挥发油组合物,可以更为便利的、精确的计算出含量或实际使用量,不论在单独、添加、或组合其他成分使用上能精确的计量和进行标准化的配制。
如有必要,本发明亦可利用生物上可接受的pH调节剂来进一步调整该植物挥发油组合物至所需的pH值,该pH调节剂包括但不限于盐酸和/或氢氧化钠。还可以为缓冲组合成分,其包括但不限于柠檬酸/硫酸氢钠硼酸盐缓冲剂、柠檬酸/柠檬酸盐缓冲剂、磷酸盐如磷酸二钠或磷酸一钠、正磷酸氢钠或磷酸氢二钠、氨丁三醇或等效的缓冲剂等加入该植物挥发油组合物中调整pH值。
根据本发明的优选实施方案,该植物挥发油组合物于干燥固化前为一黏稠状的胶体,其具有黏度范围界于2000cps至100000cps,优选为5000cps至50000cps。
本发明为一种植物挥发油组合物,进一步含有一种本领域已知的任何合适的无毒载体,其可为单一或组合。该载体与该植物挥发油的比例为可选自1~5∶1的比例范围内,优选为3∶1的比例范围。该载体可包含环糊精、麦芽糊精、纤维素、水凝胶、硅水胶、淀粉、乳糖、蔗糖、山梨糖醇、二氧化硅、滑石、硬脂酸和磷酸二钙等或其组合。优选为相对于该植物挥发油组合物整体重量上使用含量较少的载体;其中优选为在水相环境中不易溶解的载体;其中优选为在该载体和该至少一主颗粒混合达到动态平衡状态时,仍能吸附或包裹该至少一主颗粒的载体,使该至少一主颗粒不会在该平衡状态时脱离该载体。于干燥固化后的该植物挥发油组合物中,该载体的含量占该植物挥发油组合物的重量百分比为约15%至约70%的范围内,优选在约35%至约60%的范围内,更优选为在约40%至约55%的范围内。
本发明另提供一种如前所述的植物挥发油组合物的制备方法,包括下列步骤:(1)混合该至少一磷脂类材料于一水相溶液中,形成一分散溶液;(2)混合该至少一植物挥发油于该分散溶液中,使该至少一磷脂类材料包覆该至少一植物挥发油,形成至少一中间颗粒;(3)加入该至 少一界面活性剂以附接于该至少一中间颗粒,形成该至少一主颗粒;及(4)加入该载体并使该至少一主颗粒分散于该载体中。
附图说明
图1为本发明一较佳实施例的立体图。
图2为本发明一较佳实施例的制程示意图。
图3为本发明一较佳实施例的制程方块图。
图4为本发明一较佳实施例的对大鼠尿酸值的影响的长条图。
具体实施方式
本发明说明书所叙述的所有技术性及科学术语,除非另外有所定义,皆隶属于该所属领域内具有通常技术人员可共同了解的意义。以下仅以实施例说明本发明可能的实施态样,然并非用以限制本发明所欲保护的范畴,合先叙明。
本发明的术语“一”、“一个”、“该”,非以单数型式的引述,非意欲表示“有且仅一个”,亦非表示任何次序或重要性,除非有特明声明,则应是表达“一个、至少一个、或多个”的存在。
本发明的术语“约”及一般的使用范围(无论是否受术语约限定)皆意指所包含的数值并非限于本说明书所阐述的确切数值,且意指实质上在所引用范围内而不背离本发明范围的范围。如本文所使用,“约”将为本领域技术人员所知悉并了解,与测量有关的数值受到测量误差的影响会限制了它们的精度。因此,应用科学和技术文献中的一般惯例,当解释专利说明书中的值的范围时,本领域技术人员应以相同的基础进行。若本领域技术人员在使用该术语的上下文中对该术语的使用并不清楚,则“约”将意指至多具体数值的±10%。
本发明的其中一个实施例的植物挥发油组合物包括:至少一主颗粒10及一载体20。该植物挥发油组合物可为液态、半固态或干燥为固态。以下所界定的重量百分比范围,若未特别声明,是指该植物挥发油组合物于未经干燥固化时的组成状态。
各该主颗粒10包括一核层11及至少一保护层,该核层11包括至少一植物挥发油,该至少一保护层包覆该核层11且包括至少一磷脂类材料12及至少一界面活性剂13;该至少一主颗粒10分散于该载体20中。
该至少一保护层包括一第一保护层121及一第二保护层131,该至少一磷脂类材料12分布于该核层11的外表面并形成该第一保护层121,该至少一界面活性剂13分布于该第一保护层121的外表面并形成该第二保护层131,以使该植物挥发油稳定分散于该载体20中而不易聚集造成相分离。该至少一主颗粒10的有效平均粒径不大于150奈米,较佳介于40奈米至120奈米之间。其中,有效平均粒径是指利用动态光散射仪(Dynamic light scattering,简称DLS)或其他方式测定时,至少约50%的该复数主颗粒10具有该有效平均粒径。
于本发明其中一实施例中,该至少一植物挥发油可包括一种或多种自植物分离出的挥发油,该至少一植物挥发油的成分包括肉桂醛、丁香油酚、藁本内酯及萜品烯-4-醇至少其中一者。进一步说,该至少一植物挥发油可包括肉桂精油、丁香油、当归油及茶树精油至少其中一者,可依需求选用以达到不同使用效果。于固体化后的该植物挥发油组合物中,该至少一植物挥发油所占的重量百分比不小于10%,较佳介于12%至20%,以提供足够的有效成分。
于本发明其中一实施例中,该至少一磷脂类材料12及该至少一界面活性剂13的重量比介于1∶3至1∶6之间,使该至少一界面活性剂13可附接于该第一保护层121之外。该至少一磷脂类材料12包括合成或非合成的磷脂类材料12。该至少一磷脂类材料12包括合成或非合成的磷脂,该磷脂可为天然磷脂,例如:大豆卵磷脂、鸡蛋卵磷脂、磷脂酰甘油、磷脂酰肌醇、磷脂酰乙醇胺、磷脂酸、鞘磷脂、双磷脂酸磷脂等;亦可为合成磷脂,例如:二棕榈酰磷脂酰胆碱、二肉荳蔻酰磷脂酰甘油、二硬脂酰磷脂酰甘油、二硬脂酰磷脂酰胆碱及卵磷脂酰胆碱等,以及氢化或部分氢化的卵磷脂和磷脂;该磷脂亦可以是饱和的或不饱和的磷脂。于其他实施例中,该至少一磷脂类材料12及该至少一界面活性剂13的重量比亦可介于3∶1至6∶1之间,可依该至少一植物挥发油的性质选用,此时该第一保护层121可由该至少一磷脂类材料12及该至少一界面活性剂13共构而成。
本发明其中一个实施例,该至少一界面活性剂13占该植物挥发油组合物的重量百分比约2%至约30%,较佳为约2%至约18%,借以提供良好的包覆效果。该至少一界面活性剂13可包括一种或多种界面活 性剂13(较佳仅选用一种),该至少一界面活性剂13可为阳离子界面活性剂、阴离子界面活性剂、两性离子界面活性剂或非离子性界面活性剂。更进一步说,该至少一界面活性剂13的HLB值较佳为12至17,可选用单一种HLB介于于12至17的界面活性剂,或者将高HLB界面活性剂和低HLB界面活性剂以特定比例混合而得。具体而言,该至少一界面活性剂13例如但不限为水溶性维生素E、聚乙二醇、聚山梨糖醇酯、泊洛沙姆、油酰聚氧甘油酯、亚油酯酰聚氧甘油酯、氢化蓖麻油聚氧乙烯、辛酰己酰聚氧甘油酯、聚氧乙烯蓖麻油衍生物、聚氧乙烯烷醚、脂肪酸山梨糖酯、单油酸甘油酯、单亚油酸甘油酯、中链三酸甘油脂、聚油酸甘油酯、月桂基聚氧甘油酯、硬脂酰基聚氧甘油酯、丙烯乙二醇癸酸二辛酯、丙烯乙二醇月桂酸酯、丙烯乙二醇单月桂酸酯、丙烯乙二醇辛酸酯、及丙烯乙二醇单辛酸酯等中之一或其组合。于本实施例中选用聚山梨糖醇酯类作为界面活性剂系统。
该载体20的型态可为液态、半固态、固态、颗粒状等各种型态;于干燥固化后的该植物挥发油组合物中,该载体20的含量占该植物挥发油组合物的重量百分比为约15%至约70%的范围内,优选在约35%至约60%的范围内,更优选为在约40%至约55%的范围内。于本发明其中一个实施例,该载体20包括环糊精、麦芽糊精、淀粉、二氧化硅、纤维素、水凝胶、硅水胶、乳糖、蔗糖、山梨糖醇、二氧化硅、滑石、硬脂酸及磷酸二钙至少其中一者,可依需求选用。该载体20可例如呈颗粒状而可与该复数主颗粒10均匀混合,较佳地,该载体20在水相环境中不易溶解以利于该复数主颗粒10附接于其上。
于本发明的一个实施例中,该植物挥发油组合物是由如下所列的重量百分比的成分所组成:该至少一界面活性剂12%至18%、该至少一磷脂类材料2%至8%、该至少一植物挥发油5%至15%、该载体15%至25%,其余为水。进一步说,该至少一界面活性剂13包括Tween系列界面活性剂,该至少一磷脂类材料12包括卵磷脂,该至少一植物挥发油包括肉桂精油,该载体20包括二氧化硅。借此,本发明的该植物挥发油组合物于水中的溶解度不小于5000ppm,易于利用、应用范围广泛;该植物挥发油组合物的DPPH自由基清除率不小于20%,抗氧化效力优于未包覆的该植物挥发油,使用效果佳。
于本发明的一个实施例中,该植物挥发油组合物是由如下所列的重量百分比的成分所组成:该至少一界面活性剂2%至8%、该至少一磷脂类材料12%至18%、该至少一植物挥发油5%至15%、该载体15%至25%,其余为水。进一步说,该至少一界面活性剂13包括Tween系列界面活性剂,该至少一磷脂类材料12包括卵磷脂,该至少一植物挥发油包括当归油,该载体20包括二氧化硅,亦可提供良好的包覆效果。
该植物挥发油组合物可选择性地另包括一种或多种生理上可接受的风味剂,该风味剂例如但不限为天然调味剂、人造调味剂或其组合,可选择的风味可以依据相应的该植物挥发油进行选择,以具有较佳的使用感受。该植物挥发油组合物亦可选择性地含有一种或多种生理上可接受的掩味剂,该掩味剂可例如但不限为三氯蔗糖、蔗糖、糖精或其盐、果糖、右旋糖、玉米糖浆、阿斯巴甜、安赛蜜、木糖醇、山梨糖醇、赤藓糖醇、甘草酸铵、索马甜、纽甜、甘露糖醇、薄荷醇、桉树油樟脑等,借以掩盖其他材料原有的异味,以提升使用者的接受度。
出于延长稳定性的目的,该植物挥发油组合物亦可另包含有一种或多种生理上可接受的防腐剂、抗氧化剂或助流剂,以达到更长的保存期限。
该植物挥发油组合物亦可另包括生物上可接受的pH调节剂来进一步调整该植物挥发油组合物至所需的pH值,该pH调节剂包括但不限于盐酸和/或氢氧化钠,还可以为缓冲组合成分,其包括但不限于柠檬酸/硫酸氢钠硼酸盐缓冲剂、柠檬酸/柠檬酸盐缓冲剂、磷酸盐如磷酸二钠或磷酸一钠、正磷酸氢钠或磷酸氢二钠、氨丁三醇或等效的缓冲剂等。
本发明另提供一种如上所述的该植物挥发油组合物的制备方法,包括下列步骤:
步骤(1)混合该至少一磷脂类材料12于一水相溶液中,形成一分散溶液。该至少一磷脂类材料12与该水相溶液的重量比介于1∶3至1∶20之间,较佳介于1∶14至1∶18之间,另一较佳是介于1∶3至1∶5之间,可依原料性质选用以提供充分的该至少一磷脂类材料12以利于后续该植物挥发油的包覆。
步骤(2)混合该至少一植物挥发油于该分散溶液中,使该至少一磷脂类材料12包覆该至少一植物挥发油,形成至少一中间颗粒10a。该 至少一植物挥发油与该水相溶液的重量比介于1∶4至1∶12之间,较佳介于1∶8至1∶10之间。该步骤(2)的搅拌时间不小于20分钟,藉此该植物挥发油可均匀地于该分散溶液中分散成复数油滴,该至少一磷脂类材料12则可通过其亲油端及亲水端的性质差异附接于该复数油滴的外表面而形成该复数中间颗粒10a。
步骤(3)加入该至少一界面活性剂13以附接于该至少一中间颗粒10a,形成该至少一主颗粒10。要特别注意的是,该至少一界面活性剂13必须于该复数中间颗粒10a稳定形成后再添加,以避免该第一保护层121与该第二保护层131相互混合为单一层体。
步骤(4)加入该载体20并使该至少一主颗粒10分散于该载体20中。
于该步骤(1)至该步骤(4)中是保持于100rpm至300rpm的转速进行搅拌混合,以确保该植物挥发油、该至少一中间颗粒10a及该至少一主颗粒10均匀分散并与该至少一磷脂类材料12及该至少一界面活性剂13混合接触。较佳地,该步骤(1)是于70℃至90℃的温度下进行,使该至少一该磷脂类材料12水合分散于该水相溶液30中;该步骤(2)至该步骤(4)是于一低于50℃的温度下进行,避免已成形的颗粒受热崩解。相较于习知技术需分别制备水相溶液及油项溶液后再相互结合的制法,本发明的该植物挥发油组合物的制备方法可通过一锅化的操作方式完成,原料相对单纯且操作步骤简单,且无需另外添加有机溶剂,可有效提升生产效率、减少溶剂残留。
以下兹以本发明一较佳实施例1与对照例1至5进行比对说明,该至少一磷脂类材料12是选用卵磷脂;该至少一植物挥发油是选用肉桂精油;该至少一界面活性剂13是选用Tween 80;该载体20是选用二氧化硅,其商用型号可选用Syloid XDP 3050、Syloid XDP 3150或Syloid 244 FP。制备该至少一主颗粒10时,是先将10g的卵磷脂加入160毫升的水(即该水相溶液30)中并于80℃以150rpm的转速搅拌约30分钟,接着将热源移除后于30分钟内持续降温至约40℃随即加入18g的肉桂精油并以150rpm的转速搅拌约30分钟(此时反应物的温度约降为25℃),再加入40g的Tween 80并均匀混合后即可形成该至少一主颗粒10;最后再加入52g的二氧化硅以混合为具有黏度不小于范围5000至50000cps的泥状物,即制得实施例1的植物挥发油组合物。于本实 施例中,该至少一磷脂类材料12与该至少一界面活性剂13的比约为1∶4;该至少一磷脂类材料12与该水相溶液30的比为1∶16;该至少一植物挥发油与该水相溶液30的比约为1∶9。较佳地,于该步骤(4)之后另包括步骤(5):干燥移除该水相溶液30(例如冷冻干燥、喷雾干燥、鼓式干燥机干燥等各种干燥方法)以获得固体化的该植物挥发油组合物,以利于存放。该植物挥发油组合物的含水量不高于6%(较佳不高于3%),以利于保存。对照例1是以与实施例1等比例的卵磷脂及肉桂精油,于不添加该至少一界面活性剂13及该载体20的条件下制成;对照例2则以与实施例1等比例的Tween 80与肉桂精油,于不添加该至少一磷脂类材料12及该载体20的条件下制成;对照例3则以与实施例1等比例的二氧化硅与肉桂精油,于不添加该至少一磷脂类材料12及该至少一界面活性剂13的条件下制成;对照例4为实施例1无添加肉桂精油的对照组;对照例5为纯肉桂精油。各实施例及对照例的成分重量组成比例如下表所列:
Figure PCTCN2022097589-appb-000001
实施例1与对照例1至5的测试结果如下表所列,其中“水溶性提升率”是计算各实施例或对照例与肉桂精油(即对照例5)的水溶性的比值乘以100%而得;“抗氧化力提升率”是计算各实施例或对照例对DPPH清除率与对照例5的DPPH的清除率的比值乘以100%而得。需特别说明的是,各实施例及对照例系经过步骤(5)的干燥固化后,再进行水溶性的测试。由实施例1(该植物挥发油组合物)可清楚得知,通过该至少一磷脂类材料12及该至少一界面活性剂13所形成的该第一保护层121及该第二保护层131,可有效提升该植物挥发油的水溶性(提升率为389%),稳定性佳且便于搭配不同类型的该载体20,应用范围广泛。此外,相较于肉桂精油,该植物挥发油组合物的抗氧化力的提升 率更达959.3%,使用效果佳。由对照例1、2及3可知,该至少一磷脂类材料12及该至少一界面活性剂13对于该植物挥发油的水溶性提升皆有助益,且该至少一界面活性剂13与肉桂精油的相容性佳进而大幅提升其水溶性;然而,对照例2相对于对照例5的抗氧化力降低。又,由实施例1及对照例3、4的比对可知,该至少一磷脂类材料12及该至少一界面活性剂13可于水中形成粒径约45奈米至55奈米的载体20以包覆该至少一植物挥发油,稳定性及分散性佳,亦有助于提高生物利用率。
Figure PCTCN2022097589-appb-000002
较佳地,于该步骤(5)后可另包括步骤(6):细化固体化的该植物挥发油组合物至40至80网目大小;举例但不限以粉碎机或震动筛网等方式进行细化,以利于保存及后续应用(例如作为锭剂、加入乳剂等),亦可依需求细化为其他尺寸。
为进一步探讨该第一保护层121、该第二保护层131及该载体20对于该植物挥发油的保护效果,另将前述的实施例1及对照例1-3及对照例5分别于25℃及60℃的环境下保存48小时,其结果如下表所列,抗氧化力保持率是依据各实施例或对照例(保存于60℃下的DPPH清除率/保存于25℃下的DPPH清除率)×100而得。由图中可清楚得知,实施例1于60℃的高温环境下,通过该第一保护层121、该第二保护层131及该载体20,该植物挥发油组合物相较于室温下保 存的组别,抗氧化力保持率仅下降约12%,所形成的该些主颗粒10可有效保护该植物挥发油的有效成分,热稳定性佳。而对照例1-3相较于对照例5亦可提供部分的保护效果,避免肉桂精油的抗氧化力下降。通过上述实验,可预期该植物挥发油组合物具有热稳定性佳、易于保存等优点。
Figure PCTCN2022097589-appb-000003
另请参考图4,其是以前述的实施例1进行动物实验,借以评估其降尿酸效果。于动物实验中,选用体重介于150克至180克的Wistar公鼠,分成控制组、正控制组、对照组及实验组,每组只数不少于3只,所有动物进行血液采集后,先以管喂给予250mg/kg BW/d的Potassium Oxonate以诱导高尿酸,待一小时后再管喂给予对应的药剂。其中,控制组的药剂为0.5%的羧甲基纤维素钠(CMC)水溶液,正控制组的药剂为10mg/kg的Allopurinol(分散于0.5%的CMC水溶液中),对照组为75mg/kg的肉桂醛(分散于0.5%的CMC水溶液中),实验组为7.5mg/kg的实施例1的植物挥发油组合物(分散于0.5%的CMC水溶液中)。投药一小时后,进行血液采集并分析血液中的尿酸含量。图4中的尿酸含量比值是给药后血液中的尿酸含量与诱导前血液中的尿酸含量的比值,借以判断各组别的降尿酸能力。由图中的控制组及正控制组可知,此实验中的高尿酸诱导方式可确实提高动物血液中的尿酸含量,且在给予治疗药物后其尿酸含量可被降低;另由对照组可知,75mg/kg的肉桂醛可降低动物血液中的尿酸含量,而相较于肉桂醛,实施例1的植物挥发油组合物仅需使用对照组剂量的1/10即可达到相近的效果,降尿酸效果佳。
于本发明的实施例2中,该至少一植物挥发油是选用当归油,该至少一磷脂类材料12、该至少一界面活性剂13、该水相溶液30及该载体 20的种类与前述的实施例1相同,其重量百分比分别为:当归油6.4%、卵磷脂14.3%、Tween 803.6%、二氧化硅18.6%、水57.1%。通过上述的制备方法可制得粒径约145奈米的该复数主颗粒10,同样可有效包覆当归油。
以上所述是本发明的较佳实施例及其所运用的技术原理,对于本领域的技术人员来说,在不背离本发明的精神和范围的情况下,任何基于本发明技术方案基础上的等效变换、简单替换等显而易见的改变,均属于本发明保护范围之内。

Claims (20)

  1. 一种植物挥发油组合物,其特征在于,包括:
    至少一主颗粒,各该主颗粒包括一核层及至少一保护层,该核层包括至少一植物挥发油,该至少一保护层包覆该核层且包括至少一磷脂类材料及至少一界面活性剂;及
    一载体,该至少一主颗粒分散于该载体中;
    其中,该至少一植物挥发油的成分包括肉桂醛、丁香油酚、藁本内酯及萜品烯-4-醇至少其中一者。
  2. 如权利要求1所述的植物挥发油组合物,其特征在于,该至少一保护层包括一第一保护层及一第二保护层,该至少一磷脂类材料分布于该核层的外表面并形成该第一保护层,该至少一界面活性剂分布于该第一保护层的外表面并形成该第二保护层。
  3. 如权利要求1所述的植物挥发油组合物,其特征在于,该至少一磷脂类材料及该至少一界面活性剂的重量比介于1∶3至1∶6之间。
  4. 如权利要求1所述的植物挥发油组合物,其特征在于,该至少一磷脂类材料及该至少一界面活性剂的重量比介于3∶1至6∶1之间。
  5. 如权利要求1所述的植物挥发油组合物,其特征在于,于固体化后的该植物挥发油组合物中,该至少一植物挥发油所占的重量百分比不小于10%;该至少一植物挥发油包括肉桂精油、丁香油、当归油及茶树精油至少其中一者。
  6. 如权利要求1所述的植物挥发油组合物,其特征在于,该至少一主颗粒的有效平均粒径不大于150奈米。
  7. 如权利要求1所述的植物挥发油组合物,其特征在于,该至少一磷脂类材料包括合成或非合成的磷脂类材料。
  8. 如权利要求1所述的植物挥发油组合物,其特征在于,该至少一界面活性剂包括水溶性维生素E、聚乙二醇、氢化蓖麻油聚氧乙烯-40、Tween系列界面活性剂及Span系列界面活性剂至少其中一者。
  9. 如权利要求1所述的植物挥发油组合物,其特征在于,该载体包括环糊精、麦芽糊精、淀粉、二氧化硅、纤维素、水凝胶、硅水胶、乳糖、蔗糖、山梨糖醇、二氧化硅、滑石、硬脂酸及磷酸二钙至少其中一者。
  10. 如权利要求1所述的植物挥发油组合物,其特征在于,是由如下所列的重量百分比的成分所组成:该至少一界面活性剂12%至18%、该至少一磷脂类材料2%至8%、该至少一植物挥发油5%至15%、该载体15%至25%,其余为水。
  11. 如权利要求10所述的植物挥发油组合物,其特征在于,该至少一界面活性剂包括Tween系列界面活性剂,该至少一磷脂类材料包括卵磷脂,该至少一植物挥发油包括肉桂精油,该载体包括二氧化硅。
  12. 如权利要求1所述的植物挥发油组合物,其特征在于,是由如下所列的重量百分比的成分所组成:该至少一界面活性剂2%至8%、该至少一磷脂类材料12%至18%、该至少一植物挥发油5%至15%、该载体15%至25%,其余为水。
  13. 一种如权利要求1至12任一项所述的植物挥发油组合物的制备方法,其特征在于,包括下列步骤:
    混合该至少一磷脂类材料于一水相溶液中,形成一分散溶液;
    (2)混合该至少一植物挥发油于该分散溶液中,使该至少一磷脂类材料包覆该至少一植物挥发油,形成至少一中间颗粒;
    (3)加入该至少一界面活性剂以附接于该至少一中间颗粒,形成该至少一主颗粒;及
    (4)加入该载体并使该至少一主颗粒分散于该载体中。
  14. 如权利要求13所述的植物挥发油组合物的制备方法,其特征在于,于该步骤(1)中,该至少一磷脂类材料与该水相溶液的重量比介于1∶3至1∶20之间。
  15. 如权利要求13所述的植物挥发油组合物的制备方法,其特征在于,于该步骤(2)中,该至少一植物挥发油与该水相溶液的重量比介于1∶4至1∶12之间。
  16. 如权利要求13所述的植物挥发油组合物的制备方法,其特征在于,该步骤(1)于70℃至90℃的温度下进行,该步骤(2)至该步骤(4)是于一低于50℃的温度下进行。
  17. 如权利要求13所述的植物挥发油组合物的制备方法,其特征在于,于该步骤(1)至该步骤(4)中是保持于100rpm至300rpm的转速进行搅拌混合。
  18. 如权利要求17所述的植物挥发油组合物的制备方法,其特征在于,该步骤(2)的搅拌时间不小于20分钟。
  19. 如权利要求13所述的植物挥发油组合物的制备方法,其特征在于,于该步骤(4)的后另干燥移除该水相溶液以获得固体化的该植物挥发油组合物。
  20. 如权利要求19所述的植物挥发油组合物的制备方法,其特征在于,另细化固体化的该植物挥发油组合物至40至80网目大小。
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