160 results about "Adefovir" patented technology

The present invention relates to 2′-Fluoro-6′-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Heptatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varicella-Zoster Virus (VZV) and Epstein Barr virus (EBV) and secondary cancers which occur thereof (lymphoma, nasopharyngeal cancer, including drug resistant (especially including lamivudine and / or adefovir resistant) and other mutant forms of these viruses.

The present invention relates to 2′-Fluoro-6′-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Hepatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varicella-Zoster Virus (VZV) and Epstein Barr virus (EBV) and secondary cancers which occur thereof (lymphoma, nasopharyngeal cancer, including drug resistant (especially including lamivudine and / or adefovir resistant) and other mutant forms of these viruses.

The present invention is amorphous Adefuweichi ester solid matter and its preparation process. The amorphous Adefuweichi ester solid matter is solid powder obtained through solidifying oil amorphous Adefuweichi ester and has, X-ray test shows, at least 80% amorphous component. The amorphous Adefuweichi ester solid matter of the present invention is easy to filter and dry, has excellent flowability and bulk density performance, and the present invention makes it easy to produce medicine composite containing Adefuweichi ester and its suitable for industrial production.

The present invention relates to 2′-Fluoro-6′-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Heptatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varicella-Zoster Virus (VZV) and Epstein Barr virus (EBV) and secondary cancers which occur thereof (lymphoma, nasopharyngeal cancer, including drug resistant (especially including lamivudine and / or adefovir resistant) and other mutant forms of these viruses.

A compound Adefovir Dipivoxil (AD) in the form of anhydrous crystal for curing chronic hepatitis B is disclosed. It is just 9-[2-[bis(neopentanoyloxy methoxy)phosphorylmethoxy]ethyl] adenine. Its features are its high stability to light, moisture and heat. Its preparing process is also disclosed.

A crystal form of Adefovir dipivoxil, 9-[2-[[bis (neovaleroxy) methyl] phosphoroso] methoxy]ethyl] adenine, its application to treating hepatism, such as viral hepatitis, its medical composition, and the process for preparing it are disclosed.

The present invention describes a new crystal state of adefovir depivoxil and its preparation process as well as the composite of the new crystal state and its preparation process. The new crystal state and the composite are easy to prepare, stable and suitable for industrial production and storage.

A dispersing tablet of adefovirdipivoxil ester is prepared from adefovirdipivoxil ester, pregelatinized starch, microcrystalline fibres, lactose, carboxymethyl starch sodium, sodium laurylsulfate, and magnesium stearate through respective sieving, proportionally mixing and die pressing.

The present invention relates to 2′-Fluoro-6′-methylene carbocyclic nucleosides, pharmaceutical compositions containing these nucleosides and their use in the treatment or prophylaxis of a number of viral infections and secondary disease states and conditions thereof, especially including Hepatitis B virus (HBV) and secondary disease states and conditions thereof (cirrhosis and liver cancer), Heptatitis C virus (HCV), Herpes Simplex virus I and II (HSV-1 and HSV-2), cytomegalovirus (CMV), Varicella-Zoster Virus (VZV) and Epstein Barr virus (EBV) and secondary cancers which occur thereof (lymphoma, nasopharyngeal cancer, including drug resistant (especially including lamivudine and / or adefovir resistant) and other mutant forms of these viruses.

The present invention relates generally to the field of Hepatitis B variants exhibiting a reduced sensitivity to nucleoside analogues both in vivo and in vitro. More in particular, reverse transcriptase mutant rt I233V is provided. Present invention provides assays and methods for detecting such variant, which assays are useful in monitoring anti-viral therapeutic regimes and adjusting patient therapy. A diagnostic kit for detecting the presence of an HBV variant in a biological sample has also been described. Finally, the use of a farmaceutical composition to cure a subject suffering from a HBV infection, which HBV is resistant to lamuvidine and / or adefovir has been provided, which farmaceutical composition comprises the nucleoside analogue tenofovir.

The invention provides a synthetic method of anti-hepatitis B virus medicine Adefovir dipivoxil, including the steps: (1) preparing chloroethyl chloromethylether; (2) preparing chloroethyl methylether; (3) preparing 2-[bis(trifluoroethyl)-phosphoryl methoxyl] ethyl chloride; (4) preparing 9-[bis(trifluoroethoxyl)-phosphoryl methoxyl ethyl]-adenine; (5) preparing PMEA; (6) preparing 9-[bis[(isopentanoyl)methoxyl]phosphinyl]-methoxyl]adenine; it has the characters of process easy to apply, environmental protection and higher yield.

Compositions, methods and systems for treating disordered epithelial tissues, such as is caused by pathogens and / or by toxins produced thereby. The invention relates to the use of an anti-infective and / or antimicrobial active agent in a carrier, with vigorous agitation of the disordered epithelial tissue for topical treatment thereof under such conditions sufficient to achieve clinically discernable improvement of the disordered epithelial tissue. The preferred anti-infective and / or antimicrobial active agent comprises a nucleoside, such as acyclovir, valcyclovir, penciclovir, famciclovir, ganciclovir, cidofovir, adefovir, and tenofovir, and derivatives, analogs, or metabolites thereof, or a mixture thereof, or 1-docosanol, optionally in combination with an organohalide. The inventive compositions and methods may employ the use of an applicator adapted for use in promoting the penetration of the treatment composition and / or the vigorous agitation of the disordered tissue.

The invention relates to a hepatitis B virus multi-drug resistant gene locus typing detection method and a kit thereof, wherein the detection method comprises the following steps that: DNA extraction is performed, wherein PCR amplification is applied to the abstracted DNA, the used PCR primers are two pairs of positive primers and negative primers; the PCR primers contain all correlative drug resistant locuses; amplified products of PCR are subjected to LDR amplification; the used probes are probes for correlation locus, which comprise a fluorescence labeling probe and a detection probe; a sequencing machine analyzes LDR products to judge the genotype of drug resistant locus; the multi-drug resistant gene locus is a drug resistant locus of lamivudine, ADV and ETV. The hepatitis B virus multi-drug resistant gene locus typing detection kit has reliable stable result, simple and quick operation; the kit can detect the drug resistant condition of various hepatitis B viruses, and supply clinical individuation medicine application instruction to hepatitis B virus patients. The kit can reduce the ineffectivity of drugs and administration times of the patients, thereby alleviating pains and economic burden of the patients.

A chemically modified adefovir and tenofovir is prepared through the combination of adefovir (or tenofovir) with polyethanediol (or glycosylated polyethanediol). Their preparing process and their antiviral application are also disclosed.

A new crystal form of nucleotide analog 9-[2-bis(tert-amylacyloxymethoxy) phosphomethoxy ethyl] adenine (or adefovir dipivoxil-AD), its preparing process and its application are disclosed. Its process for synthesizing, purifying and preparing AD is also disclosed.

The invention provides a prodrug of a hepatitis b virus resistant drug with a liver targeting action and a preparation method for the same. The prodrug is a prodrug of Adefovir or Tenofovir. Higher fatty acid, glyceride, cholic acid compounds or the base groups of derivatives thereof with the liver targeting action are connected with Adefovir or Tenofovir to prepare the prodrug. After being taken into a human body, the prodrug is concentrated in the liver and then is decomposed, thereby having the effects of reducing the dosage, improving the curative effect, reducing the drug concentration in a kidney and reducing the toxic and side effect. The invention also provides a method for synthesizing the prodrug.

The present invention discloses an adefovir dipivoxil cholic acid class derivative and also relates to a preparation method and applications thereof at the medical aspect. The adefovir dipivoxil cholic acid class derivative is a hepatic targeting precursor drug of adefovir; compared with the adefovir dipivoxil, the adefovir dipivoxil cholic acid class derivative can improve the concentration of the adefovir in liver after being taken orally, and the adefovir dipivoxil cholic acid class derivative can be used as a preferential drug for the treatment of resisting virus and especially resisting hepatitis virus.

The invention relates to a medical composition with active components of adefovir dipivoxil and another rnucleotide (acid) anti-virus medicine and the preparation method and usage thereof. The adefovir dipivoxil and anther rnucleotide (acid) anti-virus medicine are taken as the active components, and mixed with a plurality of pharmaceutically acceptable supplements to prepare the medical composition; and the invention can be applied in treatment of viral hepatitis B. The adefovir dipivoxil and anther rnucleotide (acid) anti-virus medicine are taken as raw materials of the invention content, a plurality of supplements with special type and proportion are added, and various kinds of oral preparations such as tablet, capsule, dispersion, chewable tablet, oral disintegrating tablet, buccal tablet, dropping pill and soft capsule are prepared and developed according to the technical method described by the invention.

The invention discloses an adefovir dipivoxil (AD) as medical nucleoside compound and making method, whose chemical name is 9-[2-[[di (neopentyl acyloxy group) methoxy] oxyphosphino] methoxy] ethyl) adenine], wherein the CHARIOTEER crystal system uses Cu-K alpha irradiation, which displays characteristic adsorbing peak under X-ray powder diffraction with 2thita angle and crystal face distance (d) at 8. 2(10.9), 9. 8(9. 0), 14. 2(6. 3), 16. 5(5. 5), 17. 0(5. 2), 19. 8(4. 5), 21. 1(4. 2), 21. 5(4. 2), 22. 5(3. 9), 23. 8(3. 7), 28. 8(3. 1) and 33. 3(2. 6).

The present invention relates to medicine synthesis technology, and is especially Adefovir dipivoxil synthesizing process, which includes the following steps: 1. methylation reaction of 2-chlorethanol, paraformaldehyde and anhydrous hydrogen chloride to produce 1-chloro-2-chloromethoxyl ethane; 2. reaction of 1-chloro-2-chloromethoxyl ethane and trimorpholinyl phosphate to obtain 2-dimorpholinyl chloroethoxyl methyl phosphonate; 3. condensation of 2-dimorpholinyl chloroethoxyl methyl phosphonate and adenine in DMF in the presence of anhydrous K2CO3 catalyst to obtain 9-(2-dimorpholinylphsphonomethoxylethyl) adenine; 4. hydrochloric acid hydrolysis of 9-(2-dimorpholinylphsphonomethoxylethyl) adenine in DMF aqua to obtain 9-(2-phsphonomethoxylethyl) adenine; and 5. reaction of 9-(2-phsphonomethoxylethyl) adenine and chloromethyl pivalate in DMF under the catalysis of triethylamine to obtain Adefovir dipivoxil.

The present invention discloses one improved preparation process of Adefovir dipivalate. In the synthesis of the mother compound 9-[2-(phosphinocarboxyl methoxy) ethyl adenine, trimethyl chlorsilane, rather than expensive trimethyl bromosilane, as material and potassium iodide as nucleophilic reagentare used to reduce cost while the product yield and quality is maintained. The production process of the present invention may be used in industrial production.

The invention provides an industrialized production and synthesis process of an adefovir dipivoxil raw medicine. The synthesis process comprises the following process routes of: reacting 2-chlorohydrin subjected to cholromethylation and triisopropyl phosphite to generate an adefovir lateral chain which is condensed and hydrolyzed with adenine to generate adefovir, and then carrying out condensation on the adefovir and chloromethyl pivalate to prepare the adefovir dipivoxil product. The invention has simple process, easy operation, safety, environment protection, mild reaction condition and high product purity, uses the most elementary raw materials and common reagents, and can be used for industrialized production. The invention is used for producing the adefovir dipivoxil raw material.

The invention is an oxalic acid adefovir dipivoxil and its crystal form as well as preparing method and usage, having stable property and good fluidity, easy to purify and convenient to operate. It is chemically called oxalic acid 9-[2-[bis(pivaloyloxymethoxy)phosphorylmethoxyl]ethyl] adenine. The infrared absorption spectrum measured by KBr sheet has absorption peaks at about 3090, 2975, 1754, 1697 and 1597 cm-1; X-ray powder diffraction spectrum radiated by Cu-Ka and expressed by 20 degrees has characteristic peaks at about 3.9, 15.6, 19.6, 23.6 and 27.5. It is applied to industrialized production and widely applied to prepare the drug of curing virus hepatitis.

The invention discloses a making method of adefovir dipivoxil, which comprises the following steps: adopting 1,3-pentacyclic dioxide as raw materia; opening ring; rearranging altrose; hydrolyzing; chlorinating; proceeding N-alkylating reaction; obtaining the product with mild reacting condition, little by-product and superior object product.

The invention relates to novel use of adefovir dipivoxil or a medicinal salt thereof, and particularly relates to application in preparation of a drug for treating influenza A or B, and application in preparation of the drug for preventing the influenza A or B.

This invention provides method and test kit for synchronously detecting sub-genotypes and drug-resistant mutation of hepatitis B virus (HBV). The test kit comprises: two specific primers for amplifying gene or transcript of HBV, three specific oligonucleotide probes for detecting sub-genotypes of HBV, and thirteen specific oligonucleotide probes. The primers and the probes can also be replaced with the complementary sequences. The test kit can synchronously differentiate three sub-genotypes (B, C and D) of HBV, and detect lamivudine- and adefovir dipivoxil-resistant mutations. The test kit can reduce the detection cost.

The invention relates to adefovir dipivoxil anhydrous crystallisate. It is characterized in that : XRD: radiating with Cu-k alpha , x ray powder diffraction spectrum expressed in 2 theta having characteristic absorption peak at 3.2,6.5,8.6, 15.7,19.6,21.6, DSC: DSC converting due to absorbing heat at 80 degree; infrared absorption spectrum : KBr pellet , characteristic absorption peak being at 3287cm-1,3175cm-1,1753cm-1,1254cm-1,1147 cm-1,1025cm-1,970cm-1. The present invention also discloses adefovir dipivoxil anhydrous crystallisate preparation method and its pharmaceutical composition. The inventive adefovir dipivoxil anhydrous crystallisate dissolves quicker than 102 degree crystal form, is high in dissolution, and is stable relative to 94 degree crystal form and not easy to be hygroscopic.

The invention is a new crystallographic form of adefuwe ester, a nucleoside officinal medicine, its preparation method and a medicine, which chooses the adefuwe ester as the effective drug ingredients, used to cure the virus hepatitis.

The invention belongs to the biotechnology field and particularly relates to a multiplex ligation-dependent probe real-time fluorescence PCR (Polymerase Chain Reaction) technology for detecting the drug resistance of chronic hepatitis B. A multiplex ligation-dependent probe real-time fluorescence PCR kit comprises an MLPA (Multiplex Ligation-dependent Probe Amplification) probe set, a filling sequence and a universal primer, wherein probes are respectively designed according to mutation sites rtM204V, rtM204I, rtA181T, rtA181V and rtN236T of a P gene reverse transcription region of HBV (Hepatitis B Virus); the sequences of the probes are represented by SEQ ID NO: 1-10. The invention further relates to a method for detecting the drug resistance of the HBV lamivudine and adefovir by virtue of the kit. The method combines the high throughput of an MPLA technology, and the rapidness, sensitivity and real-time detection of real-time fluorescence PCR, and has a high coincidence rate compared with a direct sequencing method, and can be used for detecting samples which cannot be detected by the sequencing method due to insufficient sensitivity; a whole detection process takes 4-5 hours; the clinic hepatitis B drug resistance detection method provided by the invention is low in cost and quick in detection.