WO2006045238A1 - Pollen carbonisé et son emploi dans la synthèse de médicaments anticancéreux - Google Patents

Pollen carbonisé et son emploi dans la synthèse de médicaments anticancéreux Download PDF

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Publication number
WO2006045238A1
WO2006045238A1 PCT/CN2005/001609 CN2005001609W WO2006045238A1 WO 2006045238 A1 WO2006045238 A1 WO 2006045238A1 CN 2005001609 W CN2005001609 W CN 2005001609W WO 2006045238 A1 WO2006045238 A1 WO 2006045238A1
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WIPO (PCT)
Prior art keywords
pollen
agent
carbonized
group
tumor
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PCT/CN2005/001609
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English (en)
Chinese (zh)
Inventor
Hanxiang Sun
Yiping Sun
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Hanxiang Sun
Yiping Sun
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Publication of WO2006045238A1 publication Critical patent/WO2006045238A1/fr

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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
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the present invention relates to charred pollen and its use in the preparation of a medicament for treating cancer. More specifically, the present invention relates to a carbonized pollen having bio-oriented properties, used as an antitumor drug or carrier, a bio-oriented anti-tumor targeting agent based on carbonized pollen, and a carbonized pollen
  • the anti-tumor drug having bio-directing property as a carrier and a preparation method thereof, and the application of the carbonized pollen in preparing a medicament for treating cancer, treating a cardiovascular and cerebrovascular disease, and treating a rheumatoid rheumatoid drug.
  • the ideal drug is to guide the drug to the lesion area to the maximum extent, so that the drug concentration in the lesion area and the normal cell area is greatly different, so as to effectively protect normal cells and tissues from harm, which is the guiding drug.
  • lymphotactic drugs such as the use of activated carbon-based targeting agents
  • charred pollen as a carrier.
  • the inventors have conducted long-term research and a large number of experiments, and the results show that the carbonized pollen has bio-directing properties, has obvious inhibitory effect on tumors, and has a good drug-loading effect, and the present invention has been completed on the basis of this. Summary of the invention
  • a second object of the present invention is to provide an antitumor targeting agent having bio-oriented properties using carbonized pollen as a carrier and a preparation method thereof.
  • a third object of the present invention is to provide an antitumor drug having bio-oriented properties using carbonized pollen as a carrier and a preparation method thereof.
  • a fourth object of the present invention is to provide an application of carbonized pollen in the preparation of a medicament for treating cancer.
  • the invention provides a carbonized pollen having biological guiding properties and used as an antitumor drug or carrier, characterized in that the carbonized pollen is formed by carbonization, activation, purification, micronization and selection of pollen of various plants,
  • the specific surface area is 400-3000M 2 /g
  • the heavy metal content is 0.1-10ppm
  • the other soluble metal ions are 0.1-10ppm
  • the ash content is less than 5%
  • the 0.15% methylene blue adsorption value is 6-30
  • the porosity is 50%. -99.8%
  • the particle size is 20-1 OOOnm, wherein 90% of the particles have a particle size of 20-300 nm.
  • the invention provides a bio-oriented anti-tumor targeting agent with carbonized pollen as a carrier, which is characterized in that the targeting agent is composed and matched, for example, under-powder 5_100mg
  • the anti-tumor targeting agent is characterized in that the carbonized pollen raw material is selected from the pollen of various plants, such as pine pollen, ganoderma spore powder, etc., preferably pine pollen; the biological guiding agent is selected from the group consisting of nucleotides, hormones, and strontium iron.
  • the suspending agent is selected from the group consisting of polyvinylpyrrolidone, acacia, tragacanth, polyvinyl alcohol, hydroxypropylmethylcellulose, etc., preferably polyvinylpyrrolidone
  • the surfactant is selected from the group consisting of Tween Polyoxyethylene castor oil, poloxamer, etc., preferably poloxamer
  • the excipient is selected from serum albumin or gamma globulin.
  • the invention also provides a preparation method of the anti-tumor targeting agent with biological guiding properties using carbonized pollen as a carrier, characterized in that the method comprises the following steps: (1) preparing carbonized pollen particles satisfying quality requirements;
  • Adsorption biological guiding agent Under the aseptic condition, the biological guiding agent is added according to the ratio, and the mixture is mixed by slow rotation and ultrasonic treatment;
  • the excipients are added according to the ratio, and the anti-tumor target agent is obtained by freeze-drying under aseptic conditions.
  • the invention provides a bio-oriented anti-tumor drug with carbonized pollen as a carrier, characterized in that its composition and composition are as follows:
  • the anti-tumor drug is characterized in that the carbonized pollen raw material is selected from the pollen of various plants, such as pine pollen, ganoderma spore powder, etc., preferably pine pollen; the biological guiding agent is selected from the group consisting of nucleotides, hormones, strontium iron, and the like.
  • the anti-tumor active ingredient is selected from the group consisting of an anti-tumor chemotherapeutic drug, an anti-tumor radiotherapy drug, a substance that inhibits tumor angiogenesis, an anti-tumor antibody or a semi-antibody, an interferon or an anti-cancer polypeptide, etc., preferably an anti-tumor Tumor chemotherapy and radiotherapy;
  • suspending agent is selected from the group consisting of polyvinylpyrrolidone, gum arabic, tragacanth, polyvinyl alcohol, hydroxypropyl methylcellulose, etc., preferably polyvinylpyrrolidone;
  • surfactant is selected from Tween, Polyoxyethylene castor oil, poloxamer, etc., preferably poloxamer; excipient selected from serum albumin or gamma Protein.
  • the invention also provides a preparation method of an anti-tumor drug with bio-oriented properties using carbonized pollen as a carrier, characterized in that the method comprises the following steps:
  • the preparation method of the carbonized pollen particles meeting the quality requirements described in the step (1) is as follows:
  • a) Charring and activation a certain amount of pollen is placed in a ceramic dish and heated to 100-120 ° C to fully remove water, nitrogen at 300-500 ° C or carbonized under anaerobic conditions for 2-4 hours, then The carbonization is complete at 500-800 ° C, at which time superheated steam is introduced to fully activate it;
  • Dispensing and disinfection Wet quantitative dispensing, autoclaving at 120 ° C for 45 minutes, freeze-drying under sterile conditions.
  • the invention also provides the use of carbonized pollen in the preparation of a medicament for treating cancer.
  • the invention also provides the application of carbonized pollen in the preparation of cardiovascular and cerebrovascular diseases.
  • the invention also provides the application of carbonized pollen in the preparation of a medicament for treating rheumatoid rheumatoid arthritis.
  • the preparation used is a carbonized pollen microparticle that does not adsorb anti-tumor active ingredients.
  • the dosage and principle are the same as the anti-cancer preparation, which is directed to the arteriosclerotic area and the rheumatoid rheumatoid lesion through the reticuloendothelial system. The lesion is then removed by phagocytosis.
  • the administration route of the preparation of the invention is as follows: the preparation of the invention needs to pass through the blood flow and the reticuloendothelial system to function, and any administration route which can directly or indirectly enter the bloodstream or lymphatic system is suitable, preferably intravenous administration and abdominal cavity.
  • Administration in addition, can be administered intramuscularly and mucosally; since the M cells in the intestinal wall have the ability to drink less than 100 nm of microparticles, the preparation of the present invention can also be administered orally. Dosage depends on the drug and the mode of administration.
  • the recommended dose for intravenous administration adult dose (referred to as carbonized pollen content) 10 - 80mg, once every other day or twice a week, three months for a course of treatment; muscle and
  • the amount administered intraperitoneally is the same; since the preparation of the present invention is very toxic, the oral dose can be used in an amount of 1-5 g/time depending on the condition. All of the above are the doses of charred pollen, and the amount of the drug contained in the case of drug loading should be lower than the conventional dose used in clinical practice, and it is flexible according to the condition.
  • Pollen is a reproductive organ of plants. It acts as a reproductive organ and does not contain harmful heavy metals. It is especially free of lead, arsenic and other toxic substances commonly found in ordinary activated carbon. It has a uniform and good appearance. It forms carbonized pollen. After that, the internal has a good spatial structure, has a rich mesh, has a large specific surface area, and has a large non-specific physical adsorption property, and is a good drug carrier.
  • the role of tumor cells If the carbonized pollen is used as a carrier to adsorb and carry anti-tumor active ingredients, the effect of killing cancer cells is enhanced, thereby preparing various anti-tumor targeted drugs, and drugs in tumor microvasculature and tumor cell interstitial.
  • the concentration reaches tens or even hundreds of times of conventional treatment methods, which greatly enhances the anti-tumor effect and reduces the side effects of chemotherapy and radiotherapy drugs. Therefore, on the basis of using carbonized pollen particles, the dose of clinical routine chemotherapy and radiotherapy can be reduced to 10-20% of the original dose, but it can achieve better therapeutic effect than the conventional dose, and can minimize the commonly seen It is difficult to avoid the side effects of normal cells and immune system that are difficult to avoid in chemotherapy.
  • the carbonized pollen of the invention has the effects of preventing and treating vascular atherosclerosis, coronary heart disease and cerebral thrombosis, and has obvious therapeutic effects on infectious diseases such as rheumatoid rheumatism, and the mechanism is due to the presence of all lesions. Inflammation, charred pollen particles have a tendency to move toward these lesions. In the lesion area, the phagocytic cells of the phagocytic cells are foreign bodies, which induce phagocytic properties, and gradually detach the lesions during phagocytosis.
  • the pollen pollen particles are prepared by using pine pollen as raw material, and then the bio-directing agent ferroniobium is adsorbed to obtain a bio-oriented anti-tumor targeting agent (referred to as product A) with carbonized pollen as carrier.
  • product A a bio-oriented anti-tumor targeting agent with carbonized pollen as carrier.
  • Test animals CD-1 mice were provided by the Animal Center of Peking University Hospital.
  • the dosage and mode of administration Take clean male CD-1 mice, 18-22 grams, a total of 60, divided into 6 groups, 10 in each group, under the sterile conditions, each group of tail vein injection Administration, twice a week, 0.1 ml / only / time, calculate the cumulative dose.
  • the results show that the acute toxicity of the carbonized pollen of the present invention to mice is 194.13/KG, which indicates that the preparation of the present invention is less toxic and safe.
  • the carbonized pollen particles are prepared by using pine pollen as raw material, and then the biological guiding agent and the antitumor active ingredient are adsorbed, the guiding agent is ferroniobium, the antitumor active ingredient is cisplatin, and the carbonized pollen is used as the carrier.
  • Antitumor drug with bio-directing properties (referred to as product B).
  • Tumor beads S180 sarcoma is provided by the Animal Center of Peking University Hospital.
  • Test animals Clean male ICR mice, 18-22 grams, a total of 60, divided into 6 groups, 10 in each group.
  • each group was administered with tail vein injection twice a week, 0.1 ml/only/time, and the cumulative dose was calculated.
  • the tumor inhibition test design is shown in Table 2:
  • mice The tumor inhibition rate of mice, the results are shown in Table 3:
  • the dose of the cisplatin constant group is 7 m g / kg, and the dose of the 1/10 dose group is 0. 7rag/kgo
  • mice Normal control group Normal tumor-bearing dose Normal dose 1/10 dose to charred pine flower Charcoal pine pollen group Photo group Control group Drug control powder + 1/10 Number of mice (n) 10 10 10 10 10 10
  • the 1/10 dose of cisplatin is not very toxic.
  • the charred pine pollen group has a good tumor inhibition rate, which is compatible with cisplatin and enhances the antitumor effect.
  • the kidney cancer cells R11 were cultured in 1640 culture medium, and the product A was added to the cell culture flask under the condition of 2 mg/50 ml of the culture solution under sterile conditions to observe the change of the R11 cells. The observation results showed that the cancer cells stopped on the day. Growing, the next day the cancer cells devour a large number of particles and then begin to swell and rupture. The evenly distributed particles in the culture flask are enriched into the interior of the cell (the particles are almost invisible in the background of the culture flask), indicating that the particles are actively phagocytized by the cancer cells, the number of cells begins to decrease, and the cells completely dissolve into empty shells after one week. After the cancer cells actively phagocytose the microparticles, the cell generation was disturbed and the cells died. detailed description
  • Particles having a particle size ranging from 20 to 300 nm are selected.
  • Example 3 50 mg of carbonized pollen prepared in Example 1 was added to the vehicle serum albumin 1 mg, and lyophilized under sterile conditions to obtain a carbonized pollen microparticle powder injection.
  • Example 3 50 mg of carbonized pollen prepared in Example 1 was added to the vehicle serum albumin 1 mg, and lyophilized under sterile conditions to obtain a carbonized pollen microparticle powder injection.
  • Example 4 Preparation of anti-tumor targeting agents: Take 50 mg of charred pollen prepared in Example 1, add 25 mg of bio-directing agent ferroniobium under aseptic conditions, add 1 ml of deionized water, mix by slow rotation and sonicate for 10 minutes, then add excipient serum white. Protein lmg, sterile freeze-dried to obtain the product.
  • Example 4 Take 50 mg of charred pollen prepared in Example 1, add 25 mg of bio-directing agent ferroniobium under aseptic conditions, add 1 ml of deionized water, mix by slow rotation and sonicate for 10 minutes, then add excipient serum white. Protein lmg, sterile freeze-dried to obtain the product.
  • Example 4 Take 50 mg of charred pollen prepared in Example 1, add 25 mg of bio-directing agent ferroniobium under aseptic conditions, add 1 ml of deionized water, mix by slow rotation and sonicate for 10 minutes, then add excipient serum white. Protein lm
  • Example 5 (2) taking 50 mg of carbonized pollen prepared in Example 1, adding 3 parts (44.01 mg) of the above composite biological directing agent under aseptic conditions, adding 2 ml of deionized water, slowly rotating and mixing, and sonicating for 10 minutes. Then, 50 mg of excipient gamma globulin was added and lyophilized to obtain a product.
  • Example 5
  • Example 6 Take 50 mg of charred pollen prepared in Example 1, add 10 mg of ferroniobium, add 20 mg of polyvinylpyrrolidone, 10 mg of poloxamer, add 1 ml of deionized water, mix by slow rotation and sonicate for 10 minutes, then add Fu The serum albumin 1mg is prepared by lyophilization.
  • Example 6 Take 50 mg of charred pollen prepared in Example 1, add 10 mg of ferroniobium, add 20 mg of polyvinylpyrrolidone, 10 mg of poloxamer, add 1 ml of deionized water, mix by slow rotation and sonicate for 10 minutes, then add Fu The serum albumin 1mg is prepared by lyophilization.
  • Example 6 Take 50 mg of charred pollen prepared in Example 1, add 10 mg of ferroniobium, add 20 mg of polyvinylpyrrolidone, 10 mg of poloxamer, add 1 ml of deionized water, mix by slow rotation and sonicate for 10
  • Example 7 Take 50 mg of carbonized pollen prepared in Example 1, take 2 parts (29.34 mg) of the composite biological directing agent prepared in Example 4, add 5 Fu 3 mg, add 1 ml of deionized water, mix slowly and spin for 10 minutes, no The bacteria can be lyophilized.
  • Example 7 Take 50 mg of carbonized pollen prepared in Example 1, take 2 parts (29.34 mg) of the composite biological directing agent prepared in Example 4, add 5 Fu 3 mg, add 1 ml of deionized water, mix slowly and spin for 10 minutes, no The bacteria can be lyophilized.
  • Example 7 Take 50 mg of carbonized pollen prepared in Example 1, take 2 parts (29.34 mg) of the composite biological directing agent prepared in Example 4, add 5 Fu 3 mg, add 1 ml of deionized water, mix slowly and spin for 10 minutes, no The bacteria can be lyophilized.
  • Example 8 Take 100 mg of carbonized pollen prepared in Example 1, take 44.01 mg of the composite biological directing agent prepared in Example 4, add 20 mg of cisplatin, add 1 ml of deionized water, mix by slow rotation and sonicate for 10 minutes, due to cisplatin. Unstable, should be used in clinical treatment.
  • Example 8 Take 100 mg of carbonized pollen prepared in Example 1, take 44.01 mg of the composite biological directing agent prepared in Example 4, add 20 mg of cisplatin, add 1 ml of deionized water, mix by slow rotation and sonicate for 10 minutes, due to cisplatin. Unstable, should be used in clinical treatment.
  • Example 8 Take 100 mg of carbonized pollen prepared in Example 1, take 44.01 mg of the composite biological directing agent prepared in Example 4, add 20 mg of cisplatin, add 1 ml of deionized water, mix by slow rotation and sonicate for 10 minutes, due to cisplatin. Unstable, should be used in clinical
  • Example 9 Preparation of anti-tumor drugs:
  • Example 10 Take 50mg of carbonized pollen prepared in Example 1, add 50mg of ferroniobium, add 5mg of polyvinylpyrrolidone, add 1mg of poloxamer, add 20mg of doxorubicin, add 1ml of deionized water, mix by slow rotation and perform ultrasonic treatment. 10 minutes, now available.
  • Example 10 Take 50mg of carbonized pollen prepared in Example 1, add 50mg of ferroniobium, add 5mg of polyvinylpyrrolidone, add 1mg of poloxamer, add 20mg of doxorubicin, add 1ml of deionized water, mix by slow rotation and perform ultrasonic treatment. 10 minutes, now available.
  • Example 10 Take 50mg of carbonized pollen prepared in Example 1, add 50mg of ferroniobium, add 5mg of polyvinylpyrrolidone, add 1mg of poloxamer, add 20mg of doxorubicin, add 1ml of
  • paclitaxel 20 mg was dissolved in polyoxyethylene castor oil, 50 mg of carbonized pollen prepared in Example 1 was added, 29.34 mg of the composite biological directing agent prepared in Example 4 was added, and 1 ml of deionized water was added, and the mixture was slowly rotated and mixed. Ultrasonic treatment for 10 minutes, ready for use.

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract

La présente invention a pour objet un pollen carbonisé et son emploi dans la synthèse de médicaments anticancéreux. La présente invention décrit un agent antitumoral ainsi qu’un médicament antitumoral qui présentent des effets biologiques spécifiques et qui emploient ledit pollen carbonisé au titre de vecteur. Ledit agent antitumoral et ledit médicament antitumoral sont susceptibles d’augmenter de façon significative les effets antitumoraux, de réduire les effets secondaires toxiques des médicaments de chimiothérapie et de radiothérapie, ainsi que de diminuer les dégâts occasionnés aux cellules saines de l’organisme et du système immunitaire.
PCT/CN2005/001609 2004-10-25 2005-09-29 Pollen carbonisé et son emploi dans la synthèse de médicaments anticancéreux WO2006045238A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CNB2004100863182A CN1273195C (zh) 2004-10-25 2004-10-25 炭化花粉及其在制备治疗癌症药物中的应用
CN200410086318.2 2004-10-25

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114317626A (zh) * 2020-09-30 2022-04-12 北京化工大学 一种光-酶耦合级联生产环氧脂肪酸酯的方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1121832A (zh) * 1994-04-08 1996-05-08 北京市兴大科学系统公司 一种抗癌新药

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1121832A (zh) * 1994-04-08 1996-05-08 北京市兴大科学系统公司 一种抗癌新药

Non-Patent Citations (1)

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Title
Ding Anwei, Puhuangtan Paozhi Gongyi Ji Zhiliang Biaozhun Yanjiu Nanjing Zhongyiyao Daxue Xuebao, 1995, Vol.11, No.2:93-95 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114317626A (zh) * 2020-09-30 2022-04-12 北京化工大学 一种光-酶耦合级联生产环氧脂肪酸酯的方法
CN114317626B (zh) * 2020-09-30 2023-12-15 北京化工大学 一种光-酶耦合级联生产环氧脂肪酸酯的方法

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CN1634593A (zh) 2005-07-06

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