WO2006111085A1 - Procede, formulation et utilisation de medicaments ou de nutriments avec une absorption orale amelioree - Google Patents
Procede, formulation et utilisation de medicaments ou de nutriments avec une absorption orale amelioree Download PDFInfo
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- WO2006111085A1 WO2006111085A1 PCT/CN2006/000718 CN2006000718W WO2006111085A1 WO 2006111085 A1 WO2006111085 A1 WO 2006111085A1 CN 2006000718 W CN2006000718 W CN 2006000718W WO 2006111085 A1 WO2006111085 A1 WO 2006111085A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P9/12—Antihypertensives
Definitions
- the present invention relates to a method and composition formulation for altering the absorption route of an oral drug or nutrient and improving overall bioavailability, and in particular to medicinal or Nutrient methods, compositions, and uses thereof for the absorption of biologically active lipophilic, hydrophilic compounds or mixtures of both in the gastrointestinal system and for enhancing the overall bioavailability of the drug or nutrient.
- Oral administration of drugs and nutraceuticals is the most common and convenient route of administration for drugs and nutrients, and is absorbed into the blood by the gastrointestinal system by various absorption means of the drug or nutrients in the gastrointestinal tract.
- drugs or nutrients developed from natural products in the development of their oral dosage forms, due to the lipophilic or hydrophilic nature of these drugs or nutrients, their absorption in the gastrointestinal tract is affected by their presence in the human body.
- Metabolic absorption mechanism and the influence of many factors in the absorption process of human gastrointestinal tract, including the physical and chemical properties of the drug itself, the solubility and dissolution rate of the drug, the PH value at different positions in the gastrointestinal tract, the gastric emptying speed and the peristalsis , foods and other contents in the stomach and intestines, bacteria in the gastrointestinal tract, etc. Affected by these factors, some drugs or nutrients have low overall absorption rate and low bioavailability in the human body, thereby limiting the efficacy and effects of drugs or nutrients.
- the route of absorption of oral drugs or nutrients is in the gastrointestinal tract, but mainly in the intestines, because the drug stays in the stomach for a short period of time and has a small absorption area, while the intestine stays for a long time and the intestinal wall absorbs. large area.
- the drug disintegrates in the stomach. Due to environmental factors of gastric juice, such as pH, bio-enzymes and bacterial flora, and the short residence time of the drug in the stomach (usually no more than 2 hours), the drug is hydrolyzed, hydrolyzed, or precipitated in the stomach. It is difficult to be absorbed, or only a small amount of drugs can be absorbed.
- Lipophilic compounds or nutrients can be dissolved in lipids (oils) and some organic solvents while being substantially insoluble in water or very low in water solubility.
- the lack of solubility of lipophilic bioactive compounds in aqueous media is an important limiting factor limiting their therapeutic use, making it difficult to effectively administer such drugs or nutrients to patients.
- lipophilic drugs or nutrients are in oil or certain types of aqueous solutions and/or oils When administered in the form of a suspension or emulsifier, the absorption rate and bioavailability are also low.
- Bioactive hydrophilic compounds can be dissolved in water and most organic solvents.
- Such compounds are not precipitated in the above-mentioned gastrointestinal fluid environment, but are affected by acid, water, various enzymes and bacterial groups, and undergo hydrolysis and enzymatic hydrolysis in the gastrointestinal tract to become metabolites, thus ultimately The proportion of the original compound absorbed into the blood is also reduced. Since most of the components that are eventually absorbed into the blood are not the original prodrugs before oral administration, the pharmacological activity of the prototypical drugs cannot be achieved.
- saponins have been widely used in the preparation of drugs for the treatment of various diseases or for the use of nutrients such as ginsenosides.
- saponins such as notoginsenosides, such as samarium saponins or nutrients.
- Some of these compounds are hydrophilic compounds. Water-soluble saponins continue to hydrolyze or hydrolyze in the intestines when they are hydrolyzed (the chemical structure of the drug changes) and enter the intestinal tract. Only a small part can pass through the intestines.
- the flora is absorbed during metabolism.
- the fat-soluble sapogenin crystals are crystallized in the stomach or intestines in the stomach or intestines, and are almost completely incapable of being absorbed.
- panaxadiol and triol saponins are hydrophilic compounds.
- Ginsenoside is the main active ingredient in ginseng. Ginsenoside is absorbed by the digestive tract after oral administration, and the absorption rate is extremely low. For example, the absorption rate of ginsenoside Rbl is only 1%, Rh2 is 3.4%, and Rgl is 1.9% (Dong Shuhua et al.
- Hydrophilic ginsenoside compound In the above absorption process, the original saponin compound is hydrolyzed, decomposed, metabolized into secondary metabolites or the final metabolite is absorbed, so that the saponin compound can not fully exert its biological activity and pharmacology in the original form. Activity, reducing its medicinal value.
- Oral absorption forms of these drugs also present bottleneck problems encountered when the above saponins are absorbed.
- extensive research has been conducted in the pharmaceutical field to study how to control the drug without disintegrating when passing through the stomach. Entering the intestines begins to disintegrate, release, and be absorbed.
- the active ingredient of the drug or nutrient is not disintegrated or released when passing through the stomach, but is delayed to release to the intestinal site to obtain the desired specific blood drug. Concentration and bioavailability of the drug for better therapeutic results.
- the dissolved molecular state allows the drug or nutrient to be absorbed in the stomach, reduces the absorption rate of the drug in the intestinal tract, reduces or avoids various factors affecting the absorption of the drug or nutrient, and enables the drug or nutrient to The protoplast state, rather than metabolites, is effectively absorbed in the stomach and intestines, thereby increasing the overall absorption rate and bioavailability of the drug or nutrient.
- the object of the present invention is to provide a method and formulation for modifying the absorption route of an oral drug or nutrient and improving the overall bioavailability of the prior art, so that the drug or nutrient is protected before being absorbed.
- the dissolved state and the molecular state that facilitates absorption enable the drug or nutrient to be absorbed in the stomach in a large amount, reduce the absorption ratio of the drug or nutrient in the intestinal tract, and reduce or avoid various factors affecting the absorption of the drug.
- the method maintains the physical and chemical stability of the drug or nutrient containing the therapeutically effective dose in contact with the gastric juice and the intestinal absorption environment, that is, is not decomposed, destroyed and precipitated in the gastrointestinal tract by the gastric juice and intestinal environment, and can be mainly Absorbed in the stomach in large quantities, changing the traditional absorption pathways of oral drugs or nutrients mostly relying on intestinal absorption, greatly improving the overall absorption rate and bioavailability of oral drugs or nutrients.
- the method and composition formulation provided by the present invention can be applied not only to the preparation of oral preparations of water-soluble compounds and fat-soluble compounds for medicinal or nutrient use, but also more particularly to the application of water-soluble compounds and fat-soluble compounds. Preparation of oral formulations of medicinal or nutritional mixtures.
- the oral preparation of the mixture is not decomposed, destroyed and not precipitated in the gastrointestinal tract by contact with gastric juice and intestinal environment when contacted with gastric juice or intestinal absorption environment, and can be absorbed mainly in the stomach, and the oral medication or nutrient is changed. Most of the traditional absorption pathways that rely on intestinal absorption greatly enhance the overall absorption and bioavailability of oral medications.
- the method of the present invention is an oral preparation prepared by providing a specific organic solvent composition formulation, a pharmaceutically or nutritive water-soluble compound, a fat-soluble compound, or a mixture of the two.
- the oral preparation prepared by the method of the present invention can withstand the effects of acid, water, enzymes and bacteria in the gastrointestinal environment without being decomposed and precipitated.
- composition of the organic solvent provided by the present invention is a compound or a mixture of medicinal or nutraceuticals and a specific method and composition selected from the following, which is a pharmaceutical or nutritive substance including a monomer compound and a mixture with the following organic a mixture of one or more of the solvents.
- Such organic solvents include, but are not limited to, fish oil, safflower oil, refined soybean oil, refined peanut oil, evening primrose oil, milk thistle oil, grape seed oil, sunflower oil, sea buckthorn oil and other animal and vegetable oils; and ethanol, propylene glycol, Mixing one or more of organic solvents such as glycerol, polyethylene glycol, ethyl acetate, propylene carbonate, etc., and also mixing with one or more of the following acid-resistant protective agents: such acid-resistant protection Agents include, but are not limited to, the following compounds, such as Labrafil M 1944 CS, Tween 20, Tween 21, Tween 40, Tween 60, Tween 80, Tween 81, Brij, Spans (also a sorbitan fatty acid ester), polyethylene glycol 200-polyethylene glycol 600, soybean phospholipids, lecithin, polyglycerol esters, sucrose esters, polyoxyethylene products of hydrogenated vegetable oils (eg
- the formula After the formula is formulated, it can be reconstituted into a common medicinal or nutritious dosage form, such as an oral solution, a liquid capsule, a soft capsule, and the like.
- the preferred method of the present invention and the composition of the organic solvent are formulated as a water-soluble compound for medicinal or nutrient, a fat-soluble compound, or a mixture of the two, with different purity of ethanol and different proportions of hydrogenated vegetable oil.
- the polyoxyethylene product polyoxyethylene hydrogenated castor oil, Cremophor RH40
- Cremophor RH40 is mixed and prepared by the above method, and then the composition is formulated into a known oral preparation (including but not limited to oral liquid, Soft capsules, hard shell liquid capsules, and other known oral dosage forms).
- the above formulation contains a therapeutically effective amount of the drug or nutrient and is compatible with at least the polyoxyethylene product of ethanol and hydrogenated vegetable oil (polyoxyethylene hydrogenated castor oil, Cremophor RH40), or other pharmaceutically acceptable pharmaceutically acceptable carrier or Excipients, including compatibilizers, surfactants, food additives, etc.
- the method of the invention has the following features and innovations:
- the organic solvent of this particular composition formulation is only capable of dissolving biologically active hydrophilic and lipophilic compounds, as well as dissolving a mixture of hydrophilic and lipophilic.
- the special composition formulation of the present invention is characterized in that the active ingredient of the drug is mainly absorbed in the stomach, whereas the main absorption site of the drug is conventionally in the intestinal tract, and thus the present invention changes the conventional absorption site of the oral drug. 4. It can reduce the effective component to be degraded or metabolized in the gastrointestinal tract, thereby maintaining the original biological activity and pharmacological activity of the original drug, and avoiding the adverse effects that secondary metabolites may have.
- the method disclosed herein comprises the following steps: Step 1: Determine the solubility of the drug or nutrient in an organic solvent. The determination of solubility can be carried out by experimental methods well known in the art or from the literature. The formulation ratio of the drug or nutrient to the organic solvent is then determined within the solubility.
- organic solvent selected from one or more of the following organic solvents: fish oil, safflower oil, refined soybean oil, refined peanut oil, evening primrose Animal and vegetable oils such as oil, milk thistle oil, grape seed oil, sunflower oil, sea buckthorn oil, ethanol, propylene glycol, glycerol, polyethylene glycol, ethyl acetate, propylene carbonate; "
- the solution protectant is one or more of the following selected from the group consisting of: Labrafil M 1944 CS, Tween 20, Tween 21, Tween 40, Tween 60, Tween 80, Tween 81, Brij, Spans (also a sorbitan fatty acid ester), polyethylene glycol 200-polyethylene glycol 600, soybean phospholipids, lecithin, polyglycerol esters, sucrose esters, polyoxyethylene products of hydrogenated vegetable oils (eg polyoxyethylene hydrogenated castor oil) , CremophorRH40 polyoxyethylene-sorbitan fatty acid ester (eg polyoxyethylene sorbitan monolaurate, Tween 20), Nikkol HCO 40, Nikkol HCO 50 Nikkol HCO 60.
- Labrafil M 1944 CS Tween 20, Tween 21, Tween 40, Tween 60, Tween 80, Tween 81, Brij, Spans (also a sorbitan fatty acid ester), poly
- the artificial gastric juice and the artificial intestinal juice are first simulated by an experimental method well known in the art, and the above special composition containing the drug or nutrient is put into the simulated artificial gastric juice and intestinal juice for stability experiment, according to the drug solution in the simulated gastric juice. It is completely dissolved in the intestinal juice environment, stable and does not crystallize as a standard, and the ratio of the solution protective agent which does not precipitate in the gastric juice and the intestinal juice is obtained, respectively.
- the ratio of the drug or nutrient thus obtained to the above organic solvent and the above solvent protecting agent is the specific composition formulation disclosed in the present invention.
- the third step the composition of the composition containing the drug or nutrient obtained according to the foregoing steps, and then according to the pharmaceutical And the food industry production standards are prepared into known oral preparations, such as oral liquid, soft capsules, liquid capsules, etc., and flavoring agents or other edible pharmaceutical excipients or edible additives may also be added as needed.
- composition formulations provided by the present invention are:
- the content of the drug or nutrient is 5% 90% (weight, the same below), and the preferred solution is 10%-50%;
- polyoxyethylene - Sorbitan fatty acid esters eg polyoxyethylene sorbitan monolaurate, Tween 20
- Nikkol HCO 40 Nikkol HCO 50
- Nikkol HCO 60 sodium lauryl sulfate, dodecyl magnesium sulfate, ten
- the content of one or more of sodium dimercaptosulfonate, sodium tetradecyl sulfate, and glyceryl monostearate is 5% 90%, and the preferred embodiment is 12.5% 60%.
- the most preferred formulations of the special composition formulations provided by the present invention and their ratios are:
- the drug content is 5%--90% (weight, the same below), and the preferred solution is 10%-50%;
- the content of polyoxyethylene hydrogenated castor oil Cremophor RH40 as a drug solution protectant is 5%-90%, and the preferred solution is 12.5%--60%.
- the method and composition formulations of the present invention can be applied to the preparation of a pharmaceutical, nutraceutical, health product, health food, or functional food containing a biologically active hydrophilic compound, a lipophilic compound, and a mixture of the two.
- the final dosage form of the disclosed methods and compositions of the present invention includes oral liquid, oral soft gel Capsules, oral hard shell liquid capsules, or other known dosage forms, in which the active ingredient of these formulations contains the compositions of the compositions disclosed herein.
- the medicament or nutrient of the present invention refers to a bioactive lipophilic compound, a hydrophilic compound, and a mixture of the two drugs or nutrients; preferred components are selected from coumarins obtained from natural products, triterpenoid saponins or Aglycones, saponins, flavonoids, diterpenoids, sesquiterpenoids or terpenoids, including but not limited to the following types of drugs: ginsenoside Rh2, R g 3, protopanaxadiol aglycon, Original ginseng triol aglycone, ginseng total saponin, saponin, saponin, saikosaponin, diosgenin, baicalin, puerarin, genistein, soy isoflavone, ginkgolide, bilobalide, propolis, supplement Osteolipin, imperatorin, tanshinone and the like.
- the method of the present invention may also incorporate other known and pharmaceutically acceptable pharmaceutically acceptable carriers or excipients such as sweetening agents, solubilizing agents, surfactants and the like, but do not constitute an essential component of the present invention.
- the method of the invention can be prepared into an oral preparation according to different medicinal value of bioactive lipophilic and hydrophilic drugs, and is applied to anti-ulcer, analgesic, anti-hypertensive, antibacterial, antipsychotic, anti-cardiovascular diseases, Antibacterial, antipsychotic, antitumor, antimuscarinic, diuretic, anti-migraine, antiviral, anti-inflammatory, sedative, anti-diabetic, endocrine regulation, anti-aging, antidepressant, antihistamine, antiparasitic, Preparation of anti-epileptic and anti-lipid drugs.
- Figure 1 Curve of blood concentration of ginsenoside Rg3 in different dosage forms as a function of time.
- Figure 2. Curve of blood concentration of protopanaxadiol aPPD after oral administration and injection in different dosage forms over time
- Example 1 Method for determining the solubility of bioactive hydrophilic and lipophilic drugs in ethanol: In the Chinese Pharmacopoeia 2000 edition, the solubility of the drug is defined as being highly soluble, soluble, and soluble. 7 grades such as slightly soluble, slightly soluble, very slightly soluble, almost insoluble or insoluble. The corresponding requirements are as follows: Very soluble means that the solute lg (ml) can be dissolved in less than 1 ml of solvent;
- Soluble means that the solute lg (ml) can be dissolved in solvent 1- less than 10ml;
- Solution means that the solute lg (ml) can be dissolved in the solvent 10- to 30 ml;
- Slightly soluble means that the solute lg (ml) can be dissolved in the solvent 30-less than 100 ml;
- Slightly soluble means that the solute lg (ml) can be dissolved in a solvent of 100 to less than 1000 ml;
- Example 3 A method of preparing an oral preparation of a biologically active hydrophilic glycoside drug.
- Ginsenoside Rg3 is dissolved in ethanol: 100 mg of ginsenoside Rg3 of different weights are weighed and placed in a 90% ethanol solution at 25 °C ⁇ 2 °C 100 ml, vigorously vibrating every 5 minutes. Shake for 30 seconds; observe the dissolution within 30 minutes and completely dissolve.
- Example 4 A method of preparing an oral preparation of a bioactive lipophilic glycoside drug.
- the original panaxadiol saponin aPPD is dissolved in ethanol: 40 mg of the original ginseng diol saponin aPPD is weighed and placed in a 90% ethanol solution at 25 ° C ⁇ 2 ° C and 100 ml respectively. In the middle, shake vigorously for 30 seconds every 5 minutes; observe the dissolution within 30 minutes, completely dissolved.
- Example 5 Method for preparing an oral preparation of a hydrophilic lipophilic glycoside and aglycone mixture drug
- the mixture of glycosides and aglycones is dissolved in ethanol: 150 mg of the drug of different concentrations of glycosides and aglycones is weighed and placed in a 90% ethanol solution at 25 ° C ⁇ 2 ° C and 100 ml respectively. In the middle, shake vigorously for 30 seconds every 5 minutes; observe the dissolution within 30 minutes and completely dissolve.
- Example 6 Preparation of a bioactive lipophilic ginsenoside compound health care product oral preparation 1. Weigh 100 mg of protopanaxadiol saponin aPPD and 120 mg of ethanol, put the original ginseng diol saponin aPPD into ethanol, stir until all dissolved;
- Test subjects 6 adult (40-45) physical male volunteers;
- the ginsenoside R g 3 prepared according to the method of the present invention is formulated into a special composition in a formulation ratio of: ginsenoside Rg3 : 100 mg, absolute ethanol: 75 mg, polyoxyethylene hydrogenated castor oil Cremophor RH40: 175 mg.
- the special composition formulation is then made into a soft capsule according to a known method.
- Common hard shell powder capsules of ginsenoside Rg3 are commercially available on the market.
- test method for human blood concentration is as follows:
- Test subjects 12 adult (40-45) physical male volunteers;
- intravenous injection an intravenous injection of protopanaxadiol aglycone prepared according to the method of the present invention
- Hard shell powder capsule Hard containing protopanaxadiol aglycone prepared according to a generally known method Shell powder capsule
- the above experiments show that the bioavailability of the bioactive hydrophilic ginsenoside Rg3 and the bioactive lipophilic protopanaxadiol aglycone soft capsule and oral liquid prepared by the invention is much higher than the hard shell powder prepared by the traditional preparation method. capsule.
- the hard capsule prepared by the conventional preparation method is easily decomposed, precipitated, or decomposed in the gastrointestinal fluid due to the influence of the absorption environment of the gastrointestinal tract and the physical and chemical properties of the drug itself, so that the absorption in the gastrointestinal tract is poor.
- the drug solution can maintain the molecular state in the gastrointestinal fluid; and since the application of ethanol as a carrier for absorption through the gastrointestinal tract, the drug is in the ethanol At the same time, the absorption is absorbed by the gastrointestinal tract, and the drug's glucosinolates or aglycones are mainly absorbed through the intestinal tract, which greatly improves the bioavailability of the drug.
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Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008506904A JP2008536879A (ja) | 2005-04-19 | 2006-04-19 | 薬物又は栄養物の組合物調剤及び調合剤、その内服による吸収を改善する方法、及びその応用方法 |
EP06722367A EP1878445A4 (en) | 2005-04-19 | 2006-04-19 | METHOD, FORMULATION AND USE OF MEDICAMENTS OR NUTRIENTS WITH ENHANCED ORAL ABSORPTION |
US11/875,047 US20080038335A1 (en) | 2005-04-19 | 2007-10-19 | Method, formulation, and use thereof for improved oral absorption of pharmaceuticals or nutrients |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNA2005100671261A CN1853728A (zh) | 2005-04-19 | 2005-04-19 | 一种改善药物或营养物口服吸收的方法、配方及其应用 |
CN200510067126.1 | 2005-04-19 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/875,047 Continuation US20080038335A1 (en) | 2005-04-19 | 2007-10-19 | Method, formulation, and use thereof for improved oral absorption of pharmaceuticals or nutrients |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006111085A1 true WO2006111085A1 (fr) | 2006-10-26 |
Family
ID=37114715
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2006/000718 WO2006111085A1 (fr) | 2005-04-19 | 2006-04-19 | Procede, formulation et utilisation de medicaments ou de nutriments avec une absorption orale amelioree |
Country Status (5)
Country | Link |
---|---|
US (1) | US20080038335A1 (zh) |
EP (1) | EP1878445A4 (zh) |
JP (1) | JP2008536879A (zh) |
CN (1) | CN1853728A (zh) |
WO (1) | WO2006111085A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104162537A (zh) * | 2014-06-10 | 2014-11-26 | 南京农业大学 | 一种合理利用铜污染土壤的方法 |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2661812T3 (es) | 2009-10-16 | 2018-04-04 | Mochida Pharmaceutical Co., Ltd. | Composiciones |
JP5563285B2 (ja) * | 2009-12-14 | 2014-07-30 | ライオン株式会社 | 飲食品、医薬品、又は医薬部外品、並びに、プロトパナキサトリオールの安定化方法、及びプロトパナキサジオールの安定化方法 |
JP5546854B2 (ja) * | 2009-12-28 | 2014-07-09 | ライオン株式会社 | ダンマラン系トリテルペン類含有飲食品組成物及び呈味改善方法 |
MY158809A (en) * | 2010-09-22 | 2016-11-15 | Craun Res Sdn Bhd | Pharmaceutical compositions for calanolides, their derivatives and analogues, and process for producing the same |
US9510613B2 (en) | 2011-05-02 | 2016-12-06 | Lion Corporation | Panaxadiol-containing composition |
KR20190111818A (ko) * | 2018-03-23 | 2019-10-02 | 주식회사 오스테온 | 이소플라본의 생체흡수율이 증진된 조성물 |
CN111789943B (zh) * | 2019-04-08 | 2024-01-19 | 洛阳赛威生物科技有限公司 | 一种水包油佐剂组合物及其制备方法和应用 |
CN113475650B (zh) * | 2021-07-06 | 2022-12-02 | 上海百润投资控股集团股份有限公司 | 一种葡萄香精 |
WO2023014978A2 (en) * | 2021-08-06 | 2023-02-09 | Rebalance Health, Inc. | Growth hormone-releasing hormone peptides and formulations thereof |
Citations (5)
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JPH07173017A (ja) * | 1993-12-17 | 1995-07-11 | Toshio Suzuki | 松類の枯損防止用組成物及び防止方法 |
WO1998057630A1 (fr) * | 1997-06-13 | 1998-12-23 | Laboratoires Thissen (L.T.B.) | Forme pharmaceutique pour l'administration de paclitaxel, procede de preparation d'une composition de paclitaxel prete a l'emploi et utilisation de cette composition |
CN1463746A (zh) * | 2002-06-18 | 2003-12-31 | 福建科瑞药业有限公司 | 含环孢素a的微乳化预浓缩口服液 |
CN1165274C (zh) * | 1998-12-22 | 2004-09-08 | 宝洁公司 | 透明护肤组合物 |
CN1568178A (zh) * | 2001-09-10 | 2005-01-19 | 中外制药株式会社 | 紫杉醇的可注射组合物 |
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US3712947A (en) * | 1969-12-09 | 1973-01-23 | Int Flavors & Fragrances Inc | Compositions containing coumarin ether sun-screening compounds |
DE3803482A1 (de) * | 1988-02-05 | 1989-08-17 | Lohmann Therapie Syst Lts | Schwimmfaehiges orales therapeutisches system |
US6964946B1 (en) * | 1995-10-26 | 2005-11-15 | Baker Norton Pharmaceuticals, Inc. | Oral pharmaceutical compositions containing taxanes and methods of treatment employing the same |
EP0863746A1 (de) * | 1996-09-18 | 1998-09-16 | Marigen S.A. | Bioflavonol-glykosid-perester und ihre aufarbeitung zu pharmakologisch wirksamen konzentraten und ultramikroemulsionen |
WO1998032443A1 (de) * | 1997-01-24 | 1998-07-30 | Marigen S.A. | Ultramikroemulsionen aus spontan dispergierbaren konzentraten enthaltend antitumoral, antiviral und antiparasitär wirksame ester von pentacyclischen triterpenen |
US6150399A (en) * | 1998-06-30 | 2000-11-21 | Abbott Laboratories | Soy-based nutritional products |
JP2000247883A (ja) * | 1999-02-23 | 2000-09-12 | Fujisawa Pharmaceut Co Ltd | ジヒドロピリジン系化合物を含有する内服用液剤 |
US6294192B1 (en) * | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
GB9907715D0 (en) * | 1999-04-01 | 1999-05-26 | Scherer Corp R P | Pharmaceutical compositions |
US8753675B1 (en) * | 2000-01-20 | 2014-06-17 | Raj K. Chopra | Reduced form of Coenzyme Q in high bioavailability stable dosage forms and related applications |
JP4872153B2 (ja) * | 2000-12-28 | 2012-02-08 | 大正製薬株式会社 | 液体組成物 |
CA2436735A1 (en) * | 2001-02-02 | 2002-08-15 | The Regents Of The University Of California | Coumarin compounds as microtubule stabilizing agents and therapeutic uses thereof |
KR100507771B1 (ko) * | 2002-11-08 | 2005-08-17 | 한미약품 주식회사 | 난용성 감기약 활성 성분의 경구투여용 조성물 및 그의제조 방법 |
US20070166244A1 (en) * | 2006-01-19 | 2007-07-19 | The Procter & Gamble Company | Compositions comprising silicone pressure sensitive adhesives for delivering oral care substances |
-
2005
- 2005-04-19 CN CNA2005100671261A patent/CN1853728A/zh active Pending
-
2006
- 2006-04-19 WO PCT/CN2006/000718 patent/WO2006111085A1/zh not_active Application Discontinuation
- 2006-04-19 JP JP2008506904A patent/JP2008536879A/ja active Pending
- 2006-04-19 EP EP06722367A patent/EP1878445A4/en not_active Ceased
-
2007
- 2007-10-19 US US11/875,047 patent/US20080038335A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH07173017A (ja) * | 1993-12-17 | 1995-07-11 | Toshio Suzuki | 松類の枯損防止用組成物及び防止方法 |
WO1998057630A1 (fr) * | 1997-06-13 | 1998-12-23 | Laboratoires Thissen (L.T.B.) | Forme pharmaceutique pour l'administration de paclitaxel, procede de preparation d'une composition de paclitaxel prete a l'emploi et utilisation de cette composition |
CN1165274C (zh) * | 1998-12-22 | 2004-09-08 | 宝洁公司 | 透明护肤组合物 |
CN1568178A (zh) * | 2001-09-10 | 2005-01-19 | 中外制药株式会社 | 紫杉醇的可注射组合物 |
CN1463746A (zh) * | 2002-06-18 | 2003-12-31 | 福建科瑞药业有限公司 | 含环孢素a的微乳化预浓缩口服液 |
Non-Patent Citations (1)
Title |
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See also references of EP1878445A4 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104162537A (zh) * | 2014-06-10 | 2014-11-26 | 南京农业大学 | 一种合理利用铜污染土壤的方法 |
Also Published As
Publication number | Publication date |
---|---|
CN1853728A (zh) | 2006-11-01 |
EP1878445A4 (en) | 2008-06-25 |
JP2008536879A (ja) | 2008-09-11 |
US20080038335A1 (en) | 2008-02-14 |
EP1878445A1 (en) | 2008-01-16 |
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