CN117137881A - Oral medicine structure based on hollow carbonaceous nano pump and preparation method thereof - Google Patents
Oral medicine structure based on hollow carbonaceous nano pump and preparation method thereof Download PDFInfo
- Publication number
- CN117137881A CN117137881A CN202311064002.2A CN202311064002A CN117137881A CN 117137881 A CN117137881 A CN 117137881A CN 202311064002 A CN202311064002 A CN 202311064002A CN 117137881 A CN117137881 A CN 117137881A
- Authority
- CN
- China
- Prior art keywords
- hollow
- solution
- pump
- carbonaceous nano
- stirring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract 13
- 238000002360 preparation method Methods 0.000 title claims abstract 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract 8
- 238000002156 mixing Methods 0.000 claims abstract 7
- 239000006187 pill Substances 0.000 claims abstract 6
- 229940079593 drug Drugs 0.000 claims abstract 5
- 239000002702 enteric coating Substances 0.000 claims abstract 5
- 238000009505 enteric coating Methods 0.000 claims abstract 5
- 238000000034 method Methods 0.000 claims abstract 4
- 239000006185 dispersion Substances 0.000 claims abstract 3
- 239000010410 layer Substances 0.000 claims abstract 3
- 239000007788 liquid Substances 0.000 claims abstract 3
- 239000003945 anionic surfactant Substances 0.000 claims abstract 2
- 150000001720 carbohydrates Chemical class 0.000 claims abstract 2
- 238000001027 hydrothermal synthesis Methods 0.000 claims abstract 2
- 239000002736 nonionic surfactant Substances 0.000 claims abstract 2
- 239000003960 organic solvent Substances 0.000 claims abstract 2
- 238000003756 stirring Methods 0.000 claims 9
- 229940126701 oral medication Drugs 0.000 claims 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 4
- 229920001577 copolymer Polymers 0.000 claims 4
- 238000005303 weighing Methods 0.000 claims 4
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims 3
- 239000002202 Polyethylene glycol Substances 0.000 claims 3
- 125000005456 glyceride group Chemical group 0.000 claims 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims 3
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims 3
- 229920001223 polyethylene glycol Polymers 0.000 claims 3
- 239000008213 purified water Substances 0.000 claims 3
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 2
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims 2
- 239000000853 adhesive Substances 0.000 claims 2
- 230000001070 adhesive effect Effects 0.000 claims 2
- 235000011114 ammonium hydroxide Nutrition 0.000 claims 2
- 239000011248 coating agent Substances 0.000 claims 2
- 238000000576 coating method Methods 0.000 claims 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims 2
- 238000001035 drying Methods 0.000 claims 2
- 229960001021 lactose monohydrate Drugs 0.000 claims 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 239000000377 silicon dioxide Substances 0.000 claims 2
- 235000012239 silicon dioxide Nutrition 0.000 claims 2
- 239000007779 soft material Substances 0.000 claims 2
- 239000001069 triethyl citrate Substances 0.000 claims 2
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims 2
- 235000013769 triethyl citrate Nutrition 0.000 claims 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- 230000001804 emulsifying effect Effects 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 125000005395 methacrylic acid group Chemical group 0.000 claims 1
- 239000008188 pellet Substances 0.000 claims 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 238000012216 screening Methods 0.000 claims 1
- 238000007873 sieving Methods 0.000 claims 1
- 238000005507 spraying Methods 0.000 claims 1
- 238000001291 vacuum drying Methods 0.000 claims 1
- 230000004584 weight gain Effects 0.000 claims 1
- 235000019786 weight gain Nutrition 0.000 claims 1
- 238000005550 wet granulation Methods 0.000 claims 1
- 238000009825 accumulation Methods 0.000 abstract 1
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
Classifications
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
-
- 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Nutrition Science (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Physiology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides an oral medicine structure based on a hollow carbonaceous nano pump and a preparation method thereof, wherein the oral medicine structure based on the hollow carbonaceous nano pump comprises a core pill, a plurality of hollow carrier bodies adhered to the outer wall of the core pill, medicines filled in the hollow carrier bodies and an enteric coating layer coated outside the hollow carrier bodies. The hollow carrier body is a hollow carbonaceous nano pump, and the preparation method thereof is as follows: after the first solution and the second solution are subjected to hydrothermal reaction, dispersing the first solution and the second solution by an organic solvent to obtain the aqueous dispersion liquid; the first solution is obtained by mixing an anionic surfactant, a nonionic surfactant and water, and the second solution is obtained by mixing a carbohydrate and water. The drug structure release experiment shows that the pH value can be controlled to release. Meanwhile, the method is beneficial to delaying the release speed of the medicine, improving the accumulation amount of the medicines with different molecular weights and reducing the administration times, the administration amount and the toxic and side effects of the medicines.
Description
Technical Field
The invention relates to the field of medicine preparation, in particular to an oral medicine structure based on a hollow carbonaceous nano pump and a preparation method thereof.
Background
Diabetes mellitus, a metabolic disease characterized by elevated blood glucose, is classified into type i diabetes mellitus and type II diabetes mellitus according to its etiology, with type II diabetes accounting for 90%. As the prevalence of type II diabetes increases year by year and presents a trend toward younger age, it has become a global major public health problem. Effective measures are urgently needed for preventing and treating type II diabetes.
Currently, in therapeutic recommendations and guidelines for the treatment of diabetes II, the usual modes of delivery of hypoglycemic agents are injection and oral. The injection administration mode has potential injuries to patients, such as pain, bleeding, infection, allergy and the like, and fat atrophy phenomenon can occur at the injection site during the long-term administration treatment, so that the comfort of the patients is low. Patients with oral administration have better acceptance and compliance than injections. However, by oral delivery, the drugs risk degradation in the gastrointestinal tract, metabolism in the liver and digestive system side effects, reducing the absorption rate and efficiency of the drug. For example, oral administration of the cord Ma Lutai hypoglycemic agent requires special requirements for the dosage of the agent to alleviate adverse gastrointestinal reactions while ensuring adequate absorption of the cord Ma Lutai in the stomach, and thus has certain restrictions in clinical use. In addition, metformin is widely accepted and demonstrated as a first line therapeutic agent for type II diabetes, and its role in clinical treatment. However, about 30% of patients who take metformin have symptoms of digestive system dysfunction, diarrhea and vomiting, and the cause of adverse reaction after taking metformin has a large relationship with the dosage taken and the release of the drug. Thus, improvements in the route of hypoglycemic drug delivery and control of dosage are becoming a major issue.
Although treatment regimens for type II diabetes are diverse and patient compliance is relatively high, there are adverse events associated with improper selection of therapeutic agents, or improper dosage. Therefore, the intervention measures are customized to further reduce the toxic and side effects of the medicine, improve the effectiveness of the medicine and the comfort level of the patient, and have great significance.
Disclosure of Invention
Aiming at the defects existing in the prior art, one of the purposes of the invention is to provide an oral medicine structure based on a hollow carbonaceous nano pump and a preparation method thereof, which solves the problems that the oral medicine at the present stage can take hypoglycemic medicine as an example, the absorptivity and the effective rate are low, the dosage control is difficult, adverse events of the administration process are frequent, and the like. Provides a hollow carbon nano pump medicine which can be orally taken, can control the release of the medicine, improve the curative effect of the medicine and reduce the toxic and side effects of the medicine.
An oral medicine structure based on a hollow carbonaceous nano pump comprises a core pill, a plurality of hollow carrier bodies adhered on the outer wall of the core pill, medicine filled in the hollow carrier bodies and an enteric coating layer coated outside the hollow carrier bodies.
Further, the hollow carrier body is a hollow carbonaceous nano pump, and the preparation method thereof comprises the following steps: after the first solution and the second solution are subjected to hydrothermal reaction, dispersing the first solution and the second solution by an organic solvent to obtain the aqueous dispersion liquid; the first solution is obtained by mixing an anionic surfactant, a nonionic surfactant and water, and the second solution is obtained by mixing a carbohydrate and water.
Further, the core pill comprises the following components in parts by weight: 30 parts of hollow carbonaceous nano pump filled with medicine, 90 parts of caprylic/capric acid polyethylene glycol glyceride, 55 parts of silicon dioxide, 200 parts of microcrystalline cellulose, 75 parts of lactose monohydrate, 25 parts of croscarmellose sodium and 25 parts of hydroxypropyl methylcellulose.
Further, the enteric coating layer comprises the following components in parts by weight: 75.8 parts of copolymer, 37.9 parts of talcum powder, 11.4 parts of triethyl citrate and water.
Further, 1mol/L ammonia water is also included.
Further, the copolymer is a copolymer of methacrylic acid and methyl methacrylate, or an aqueous dispersion of a copolymer of methacrylic acid and ethyl acrylate.
Further, the mass ratio of methacrylic acid to methyl methacrylate was 1:2.
Further, the mass ratio of methacrylic acid to methyl methacrylate was 1:1.
The invention also provides a preparation method of the oral drug structure based on the hollow carbonaceous nano pump, which comprises the following steps:
step one, weighing part of caprylic/capric acid polyethylene glycol glyceride and silicon dioxide, and uniformly mixing and stirring for later use;
step two, weighing hydroxypropyl methylcellulose, adding the hydroxypropyl methylcellulose into purified water, stirring and dissolving, and then adding caprylic/capric acid polyethylene glycol glyceride, stirring uniformly to obtain an adhesive;
step three, weighing the hollow carbonaceous nano pump filled with the medicine and the microcrystalline cellulose according to an equal progressive mode, uniformly mixing, then adding the mixed material in the step 1, and then adding lactose monohydrate and croscarmellose sodium, uniformly mixing and stirring;
step four, adding the adhesive in the step two into the step three, and performing wet granulation to obtain a soft material;
pouring the soft material into an extruder, extruding, and screening with a screen of 0.5mm to obtain an extrudate;
step six, putting the extrudate into a rounding machine for rounding;
step seven, after rounding, putting the mixture into a vacuum drying oven for drying, and obtaining plain pills after drying;
step eight, preparing an enteric coating;
and step nine, putting the dried plain pills into a fluidized bed, and performing bottom spraying coating to obtain the oral medicine of the hollow carbonaceous nano pump. The temperature is controlled between 30 and 35 ℃, and the weight gain of the coating is about 25 percent.
Further, the preparation method of the step eight comprises the following steps: preparation of enteric coating liquid pH7.0 (S100): weighing S100, adding the mixture into purified water, stirring for 5-10 minutes, slowly dripping 1mol/L ammonia water solution, stirring for 1 hour, adding triethyl citrate, and stirring for 1 hour; and (3) adding talcum powder into the purified water, stirring for 10 minutes, emulsifying for 10 minutes, cooling, adding into the solution of S100, continuously stirring for 10 minutes, and finally sieving the solution.
Further, the preparation method of the step eight comprises the following steps: preparation of enteric coating solution (L100) at ph 6.0: weighing L100, adding the L100 into purified water, stirring for 5-10 minutes, slowly dripping 1mol/L ammonia water solution, stirring for 1 hour, adding triethyl citrate, and stirring for 1 hour;
adding talcum powder into purified water, stirring for 10min, emulsifying for 10min, cooling, adding into L100 solution, stirring for 10min, and sieving;
further, the preparation method of the step eight comprises the following steps: formulation of enteric coating solution pH5.5 (MAE 30 DP): weighing MAE 30DP, adding triethyl citrate, and stirring for 10 minutes; and (3) adding talcum powder into purified water, stirring for 10 minutes, emulsifying for 10 minutes, cooling, adding into the solution of MAE 30DP, continuously stirring for 1 hour, and finally sieving the solution.
Further, the medicine filled in the hollow carrier body has a loading molecular weight of 100 to 4000.
Further, the coating comprises an enteric coating having a thickness of 10-3000 μm.
Further, the size of the oral hollow carbonaceous nano-pump drug structure is 10-2500 μm.
Further, the particle size of the hollow carbonaceous nano pump is 100nm-20 mu m.
Further, the hollow carbonaceous nano pump has better stability, namely pH dependence, in the Zeta potential range of + -40- + -60.
Further, the hollow carbonaceous nano-pump surfactant comprises: anionic, nonionic and cationic surfactants.
Further, the Young's modulus of the hollow carbonaceous nano pump ranges from 1MPa to 10GPa.
Further, the specific surface area of the hollow carbonaceous nano pump is in the range of 50-600m 2 /g。
The invention adopts the following technical scheme:
an oral medicine structure based on a hollow carbonaceous nano pump comprises a core pill, a plurality of hollow carrier bodies adhered on the outer wall of the core pill, medicine filled in the hollow carrier bodies and an enteric coating layer coated outside the hollow carrier bodies.
Further, the hollow carrier body is a hollow carbonaceous nano pump, and the preparation method thereof comprises the following steps: the first solution and the second solution are subjected to hydrothermal reaction and then are dispersed by an organic solvent to obtain the aqueous dispersion liquid; the first solution is obtained by mixing an anionic surfactant, a nonionic surfactant and water, and the second solution is obtained by mixing a carbohydrate and water.
Further, the core pill comprises the following components in parts by weight: 30 parts of hollow carbonaceous nano pump filled with medicine, 90 parts of caprylic/capric acid polyethylene glycol glyceride, 55 parts of silicon dioxide, 200 parts of microcrystalline cellulose, 75 parts of lactose monohydrate, 25 parts of croscarmellose sodium and 25 parts of hydroxypropyl methylcellulose.
Further, the enteric coating layer comprises the following components in parts by weight: 75.8 parts of copolymer, 37.9 parts of talcum powder, 11.4 parts of triethyl citrate and water.
Further, 1mol/L ammonia water is also included.
Further, the copolymer is a copolymer of methacrylic acid and methyl methacrylate, or an aqueous dispersion of a copolymer of methacrylic acid and ethyl acrylate.
Further, the mass ratio of methacrylic acid to methyl methacrylate was 1:2.
Further, the mass ratio of methacrylic acid to methyl methacrylate was 1:1.
The invention also provides a preparation method of the oral drug structure based on the hollow carbonaceous nano pump, which comprises the following steps:
step one, weighing part of caprylic/capric acid polyethylene glycol glyceride and silicon dioxide, and uniformly mixing and stirring for later use;
step two, weighing hydroxypropyl methylcellulose, adding the hydroxypropyl methylcellulose into purified water, stirring and dissolving, and then adding caprylic/capric acid polyethylene glycol glyceride, stirring uniformly to obtain an adhesive;
step three, weighing the hollow carbonaceous nano pump filled with the medicine and the microcrystalline cellulose according to an equal progressive mode, uniformly mixing, then adding the mixed material in the step 1, and then adding lactose monohydrate and croscarmellose sodium, uniformly mixing and stirring;
step four, adding the adhesive in the step two into the step three, and performing wet granulation to obtain a soft material;
pouring the soft material into an extruder, extruding, and screening with a screen of 0.5mm to obtain an extrudate;
step six, putting the extrudate into a rounding machine for rounding;
step seven, after rounding, putting the mixture into a vacuum drying oven for drying, and obtaining plain pills after drying;
step eight, preparing an enteric coating;
and step nine, putting the dried plain pills into a fluidized bed, and performing bottom spraying coating to obtain the oral medicine of the hollow carbonaceous nano pump. The temperature is controlled between 30 and 35 ℃, and the weight gain of the coating is about 25 percent.
Further, the preparation method of the step eight comprises the following steps: preparation of enteric coating liquid pH7.0 (S100): weighing S100, adding the mixture into purified water, stirring for 5-10 minutes, slowly dripping 1mol/L ammonia water solution, stirring for 1 hour, adding triethyl citrate, and stirring for 1 hour; and (3) adding talcum powder into the purified water, stirring for 10 minutes, emulsifying for 10 minutes, cooling, adding into the solution of S100, continuously stirring for 10 minutes, and finally sieving the solution.
Further, the preparation method of the step eight comprises the following steps: preparation of enteric coating solution (L100) at ph 6.0: weighing L100, adding the L100 into purified water, stirring for 5-10 minutes, slowly dripping 1mol/L ammonia water solution, stirring for 1 hour, adding triethyl citrate, and stirring for 1 hour; adding talcum powder into purified water, stirring for 10min, emulsifying for 10min, cooling, adding into L100 solution, stirring for 10min, and sieving;
further, the preparation method of the step eight comprises the following steps: formulation of enteric coating solution pH5.5 (MAE 30 DP): weighing MAE 30DP, adding triethyl citrate, and stirring for 10 minutes; and (3) adding talcum powder into purified water, stirring for 10 minutes, emulsifying for 10 minutes, cooling, adding into the solution of MAE 30DP, continuously stirring for 1 hour, and finally sieving the solution.
Further, the medicine filled in the hollow carrier body has a loading molecular weight of 100 to 4000.
Further, the coating comprises an enteric coating having a thickness of 10-3000 μm.
Further, the size of the oral hollow carbonaceous nano-pump drug structure is 10-2500 μm.
Further, the particle size of the hollow carbonaceous nano pump is 100nm-20 mu m.
Further, the hollow carbonaceous nano pump has better stability, namely pH dependence, in the Zeta potential range of + -40- + -60.
Further, the hollow carbonaceous nano-pump surfactant comprises: anionic, nonionic and cationic surfactants.
Further, the Young's modulus of the hollow carbonaceous nano pump ranges from 1MPa to 10GPa.
Further, the specific surface area of the hollow carbonaceous nano pump is in the range of 50-600m 2 /g。
Compared with the prior art, the invention has the following characteristics and beneficial effects:
(1) The hollow carbonaceous nano pump oral medicine provided by the invention has different pH responses, the size of the medicine is controllable, the preparation process is simple, and the performance of the medicine is not affected.
(2) The hollow carbonaceous nano pump material based on structural modification provided by the invention can realize loading of medicines with different molecular weights of 100-4000, and plays an important role in medicine loading of the material due to the stirring rotation speed and the environmental pressure value during medicine loading. The uniform stirring in the filling process can ensure that the medicines are uniformly distributed and simultaneously contact with the materials, and the medicines can be fully filled into the internal cavity of the materials by regulating and controlling the environmental pressure.
(3) The application of the hollow carbon nano pump material carrier medicine based on the structural modification in preparing the hypoglycemic medicine has a regulating effect on the release of the medicine, namely, the release speed of the medicine is reduced, the release time of the medicine is prolonged, the accumulation of medicines with different molecular weights is further improved, and the administration times, the administration amount and the toxic and side effects of the medicine are reduced.
(4) According to the preparation method of the hollow carbonaceous nano pump material carrier drug based on the structural modification, provided by the invention, the surfactant in the inner space of the modified filling material is eluted, the inner space of the material is enlarged, and the drug loading capacity can be effectively increased.
(5) The appearance, the size and the related physicochemical properties of the hollow carbonaceous nano pump are further clarified through the characterization means.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The main objects and other advantages of the invention may be realized and attained by means of the instrumentalities and particularly pointed out in the specification and claims.
Drawings
FIG. 1 is a graph showing the comparison of the therapeutic effects of hollow carbonaceous nano-pump oral hypoglycemic drugs prepared by enteric coating solutions with pH7.0, pH6.0 and pH 5.5;
FIG. 2 is a graph showing the distribution of N-P-1 particle diameters;
FIG. 3 is a graph showing the distribution of N-P-2 particle size;
FIG. 4 is an SEM schematic diagram of a structure-modified hollow carbonaceous nano-pump material prepared by heating a hollow carbonaceous nano-pump at 200 ℃ for 3min modification;
FIG. 5 is an unfilled SEM schematic of the hollow carbonaceous nanopump lumen;
FIG. 6 is a schematic SEM diagram of a hollow carbonaceous nano-pump in a small volume state;
FIG. 7 is a schematic view of the surface roughness SEM of a hollow carbonaceous nano pump;
FIG. 8 is a schematic of a hollow carbonaceous nanopump mass soft SEM;
fig. 9 is an SEM schematic of a structurally modified hollow carbonaceous nano-pump material prepared by modification with 50% ethanol solution at 40 ℃ with ultrasound for 60 min.
Fig. 10 is an SEM schematic of a structurally modified hollow carbonaceous nano-pump material prepared by modification with 50% ethanol solution at 40 ℃ with ultrasound for 120 min.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The invention provides an oral medicine structure based on a hollow carbonaceous nano pump, which comprises a core pill, a plurality of hollow carrier bodies adhered to the outer wall of the core pill, medicines filled in the hollow carrier bodies and an enteric coating layer coated outside the hollow carrier bodies.
Wherein, the hollow carrier body is a hollow carbonaceous nano pump, and the preparation method thereof is as follows: after the first solution and the second solution are subjected to hydrothermal reaction, dispersing the first solution and the second solution by an organic solvent to obtain the aqueous dispersion liquid; the first solution is obtained by mixing an anionic surfactant, a nonionic surfactant and water, and the second solution is obtained by mixing a carbohydrate and water. Further, the particle size of the hollow carbonaceous nano pump is 100nm-20 mu m. The hollow carbonaceous nano pump has better stability in the Zeta potential range of + -40- + -60, namely pH dependence. The hollow carbonaceous nano-pump surfactant comprises: anionic, nonionic and cationic surfactants. Young's modulus of the hollow carbonaceous nano pump ranges from 1MPa to 10GPa. The specific surface area of the hollow carbonaceous nano pump is between 50 and 600m 2 /g。
Wherein the first solution is obtained by mixing an anionic surfactant, a nonionic surfactant and water, and the second solution is obtained by mixing a carbohydrate and water.
The mass ratio of the anionic surfactant to the nonionic surfactant is 1:1-1:10; the mass of anionic surfactant and nonionic surfactant and the ratio of water are in the range of 1g:20mL-1g:350mL; the ratio of carbohydrate to water is in the range of 1g:10mL-1g:15mL; the volume ratio of the first solution to the second solution is 1:2.
The hydrothermal reaction temperature is 160 ℃, the reaction time is 21-60 hours, and the hollow carbonaceous nano pump material is obtained after cooling, suction filtration, washing and drying after the hydrothermal reaction; wherein, the water filter membrane with the thickness of 0.45 mu m is adopted for suction filtration, deionized water is used for washing for 4 times, the drying temperature is 50-100 ℃, and the drying time is 2-24 hours.
Dispersing the material in an organic solvent, centrifuging after ultrasonic treatment, and drying to obtain the hollow carbon nano pump material with the modified structure; the organic solvent is ethanol solution with the concentration of 50-100%, and the temperature of ultrasound is 20-40 ℃; the ultrasonic time is 60-120 min; the centrifugal speed is 4500-9500rpm/min, and the centrifugal time is 3-10min; the drying temperature is 50-100 ℃ and the drying time is 2-24h.
Dispersing the material in an organic solvent, centrifuging after ultrasonic treatment, and drying to obtain the hollow carbon nano pump material with the modified structure; the organic solvent is ethanol solution with the concentration of 50 percent, and the temperature of ultrasonic treatment is 40 ℃; the ultrasonic time is 60min; the centrifugal speed is 7500rpm/min, and the centrifugal time is 5min; the drying temperature is 60 ℃ and the drying time is 4 hours.
Dispersing the material in 100-4000 different molecular weight medicine solution to be carried, and loading under pressure regulated environment to obtain the carrier medicine with the environmental pressure value of-1-1.2 kg/cm 2 The loading time is 1-8 h.
Example 1 of the hollow carbonaceous nanopump preparation described above:
the preparation of the hollow carbonaceous nano pump material with the modified structure comprises the following steps:
step one, mixing sodium oleate, P123 and water to obtain a first solution, and mixing D-ribose and water to obtain a second solution.
Wherein, the ratio of sodium oleate to P123 is 1:1.2, the mass sum of sodium oleate and P123 in the first solution to water is 1g:250mL, the ratio of D-ribose to water is 1g:13mL, and the volume ratio of the first solution to the second solution is 1:2.
And step two, fully mixing the first solution and the second solution, and carrying out hydrothermal reaction at 160 ℃ for 21h.
And thirdly, after the hydrothermal reaction, washing the obtained reactant with water, carrying out suction filtration on a reaction solution system by using a 0.45 mu m water-based filter membrane, washing with deionized water for 4 times, and drying the suction-filtered substance at 50-60 ℃ for 4-5 hours to obtain the hollow carbonaceous nano pump material.
Dispersing the obtained hollow carbonaceous nano pump material in 50% ethanol solution, performing ultrasonic treatment at 40 ℃ for 60min, and centrifuging at 7500rpm/min for 5min to obtain a hollow carbonaceous nano pump with modified structure; wherein, the ratio of the hollow carbonaceous nano pump to the 50% ethanol solution is 1g:250mL.
As shown in fig. 9, the internal space surfactant of the hollow carbon nano pump with modified structure obtained by modifying the ethanol solution with different proportions is basically removed, and the material structure is perfect.
Example 2 preparation of hollow carbonaceous nanopump:
the preparation of the hollow carbonaceous nano pump material with the modified structure comprises the following steps:
step one, mixing sodium oleate, P123 and water to obtain a first solution, and mixing D-ribose and water to obtain a second solution.
Wherein, the ratio of sodium oleate to P123 is 1:1.2, the mass sum of sodium oleate and P123 in the first solution to water is 1g:250mL, the ratio of D-ribose to water is 1g:13mL, and the volume ratio of the first solution to the second solution is 1:2.
And step two, fully mixing the first solution and the second solution, and carrying out hydrothermal reaction at 160 ℃ for 21h.
And thirdly, after the hydrothermal reaction, washing the obtained reactant with water, carrying out suction filtration on a reaction solution system by using a 0.45 mu m water-based filter membrane, washing with deionized water for 4 times, and drying the suction-filtered substance at 50-60 ℃ for 4-5 hours to obtain the hollow carbonaceous nano pump material.
And fourthly, dispersing the obtained hollow carbonaceous nano pump material in 50% ethanol solution, performing ultrasonic treatment at 40 ℃ for 120min, and centrifuging at 7500rpm/min for 5min to obtain the hollow carbonaceous nano pump with modified structure. Wherein, the ratio of the hollow carbonaceous nano pump to the 50% ethanol solution is 1g:250mL.
As shown in fig. 10, the hollow carbon nano pump with modified structure is obtained by adjusting different ultrasonic time modification, the surfactant in the inner space is basically removed, the material structure is perfect, and the roughness of the surface of the material can be changed, namely, under the condition, the surface of the modified hollow carbon nano material is rough, which has important significance for regulating and controlling the adsorption quantity of the medicine.
Example 3 preparation of hollow carbonaceous nanopump:
the preparation of the hollow carbonaceous nano pump material with the modified structure comprises the following steps:
step one, mixing sodium oleate, P123 and water to obtain a first solution, and mixing D-ribose and water to obtain a second solution.
Wherein, the ratio of sodium oleate to P123 is 1:1.2, the mass sum of sodium oleate and P123 in the first solution to water is 1g:250mL, the ratio of D-ribose to water is 1g:13mL, and the volume ratio of the first solution to the second solution is 1:2.
And step two, fully mixing the first solution and the second solution, and carrying out hydrothermal reaction at 160 ℃ for 21h.
And thirdly, after the hydrothermal reaction, washing the obtained reaction with water, carrying out suction filtration on a reaction solution system by using a 0.45 mu m water-based filter membrane, washing with deionized water for 4 times, and drying the suction-filtered substance at 50-60 ℃ for 4-5 hours to obtain the hollow carbonaceous nano pump.
And step four, heating the obtained hollow carbonaceous nano pump for 3min at the temperature of 200 ℃ to obtain the hollow carbonaceous nano pump with modified structure.
As shown in fig. 4, which is a schematic diagram of filling the inner cavity of the hollow carbonaceous nano pump, the surfactant is still filled in the inner space of the material by adjusting different modification conditions to obtain the hollow carbonaceous nano pump with modified structure.
Example 4 preparation of hollow carbonaceous nanopump:
the preparation of the hollow carbonaceous nano pump material with the modified structure comprises the following steps:
step one, mixing sodium oleate, P123 and water to obtain a first solution, and mixing D-ribose and water to obtain a second solution.
Wherein, the ratio of sodium oleate to P123 is 1:1.2, the mass sum of sodium oleate and P123 in the first solution to water is 1g:250mL, the ratio of D-ribose to water is 1g:13mL, and the volume ratio of the first solution to the second solution is 1:2.
And step two, fully mixing the first solution and the second solution, and carrying out hydrothermal reaction at 160 ℃ for 21h.
And thirdly, after the hydrothermal reaction, washing the obtained reactant with water, carrying out suction filtration on a reaction solution system by using a 0.45 mu m water-based filter membrane, washing with deionized water for 4 times, and drying the suction-filtered substance at 50-60 ℃ for 4-5 hours to obtain the hollow carbonaceous nano pump material.
Dispersing the obtained hollow carbonaceous nano pump material in 50% ethanol solution, performing ultrasonic treatment at 40 ℃ for 60min, and centrifuging at 7500rpm/min for 5min to obtain a hollow carbonaceous nano pump with modified structure; wherein, the ratio of the hollow carbonaceous nano pump to the 50% ethanol solution is 1g:250mL.
Fig. 5 is a schematic diagram of a structure-modified hollow carbonaceous nano pump material and an unfilled inner cavity prepared by modifying with 50% ethanol solution at 40 ℃ in an ultrasonic mode for 60min, and the structure of the material is intact by basically removing the surfactant in the inner space of the structure-modified hollow carbonaceous nano pump obtained by modifying with ethanol solutions in different proportions.
The hollow carbonaceous nano pump has better stability in the Zeta potential range of + -40- + -60, namely pH dependence.
1. Precisely weighing 0.0031g of the hollow carbonaceous nano pump with modified structure, namely an N-P-1 sample, and placing the hollow carbonaceous nano pump in an EP tube; placing 0.0032g of the unstructured modified hollow carbonaceous nano pump, namely an N-P-2 sample, in an EP tube, respectively adding 3mL of buffer solution, and carrying out water bath ultrasonic treatment for 5min; see fig. 2, 3.
2. And (3) transferring 950 mu L of buffer solution into an EP tube, sucking 50 mu L of sample solution into the buffer solution, and uniformly mixing on a vibrator to be tested.
Sample test result table
According to a material Span value calculation formula: the Span values of the two samples obtained by the calculation of D90-D10/D50 are smaller than 0.5, and the uniformity is good.
Meaning of measuring Zeta potential: the value of the Zeta potential is related to the stability of colloidal dispersions, and the Zeta potential is a measure of the strength of the mutual repulsion or attraction between particles, the smaller the molecule or dispersed particle, the higher the Zeta potential, i.e. positive or negative, the more stable the system, i.e. resistant to aggregation after dissolution or dispersion. Conversely, the lower the Zeta potential, i.e., positive or negative, the more prone it is to coagulation or agglomeration, i.e., the attractive force exceeds the repulsive force, and the dispersion is broken and coagulation or agglomeration occurs.
The core pill comprises the following components in parts by weight: 30 parts of hollow carbonaceous nano pump filled with medicine, 90 parts of caprylic/capric acid polyethylene glycol glyceride, 55 parts of silicon dioxide, 200 parts of microcrystalline cellulose, 75 parts of lactose monohydrate, 25 parts of crosslinked sodium carboxymethyl cellulose and 25 parts of hydroxypropyl methyl fiber.
Further, the enteric coating layer comprises the following components in parts by weight: 75.8 parts of copolymer, 1mol/L ammonia water, 37.9 parts of talcum powder, 11.4 parts of triethyl citrate and water. The copolymers are respectively: s100, namely a copolymer of methacrylic acid and methyl methacrylate, wherein the mass ratio is 1:2; or L100, i.e. the mass ratio of methacrylic acid to methyl methacrylate copolymer is 1:1, or MAE 30DP, i.e. the aqueous copolymer dispersion of methacrylic acid and ethyl acrylate. Ammonia was used only for the preparation of both S100 and L100 solutions.
The drug filled in the hollow carrier body may have a loading molecular weight of 100 to 4000. The coating comprises enteric coating, and the thickness of the coating is 10-3000 μm. The size of the hypoglycemic medicine structure is 10-2500 μm.
The preparation method of the oral medicine structure based on the hollow carbonaceous nano pump specifically comprises the following steps:
step one, weighing part of caprylic/capric acid polyethylene glycol glyceride and silicon dioxide, and uniformly mixing and stirring for later use;
step two, weighing hydroxypropyl methyl fiber, adding the hydroxypropyl methyl fiber into purified water, stirring and dissolving, and then adding caprylic/capric acid polyethylene glycol glyceride, stirring uniformly to obtain an adhesive;
step three, weighing the hollow carbonaceous nano pump filled with the medicine and the microcrystalline cellulose according to an equal progressive mode, uniformly mixing, then adding the mixed material in the step 1, and then adding lactose monohydrate and croscarmellose sodium, uniformly mixing and stirring;
step four, adding the adhesive in the step two into the step three, and performing wet granulation to obtain a soft material;
pouring the soft material into an extruder, extruding, and screening with a screen of 0.5mm to obtain an extrudate;
step six, putting the extrudate into a rounding machine for rounding;
step seven, after rounding, putting the mixture into a vacuum drying oven for drying, and obtaining plain pills after drying;
step eight, preparing an enteric coating;
and step nine, putting the dried plain pills into a fluidized bed, and performing bottom spraying coating to obtain the oral medicine of the hollow carbonaceous nano pump. The temperature is controlled between 30 and 35 ℃, and the weight gain of the coating is about 25 percent.
The hollow carbonaceous nanopump was filled with semaglutin, wherein the enteric coating provides the following three examples:
example 1, preparation of step eight:
preparation of enteric coating liquid with pH7.0, namely S100: weighing S100, adding the mixture into purified water, stirring for 5-10 minutes, slowly dripping 1mol/L ammonia water solution, stirring for 1 hour, adding triethyl citrate, and stirring for 1 hour; adding talcum powder into purified water, stirring for 10min, emulsifying for 10min, cooling, adding into the solution of S100, stirring for 10min, and sieving;
example 2, preparation of step eight:
preparation of enteric coating liquid with pH of 6.0, namely L100: weighing L100, adding the L100 into purified water, stirring for 5-10 minutes, slowly dripping 1mol/L ammonia water solution, stirring for 1 hour, adding triethyl citrate, and stirring for 1 hour;
adding talcum powder into purified water, stirring for 10min, emulsifying for 10min, cooling, adding into L100 solution, stirring for 10min, and sieving;
example 3, preparation of step eight:
formulation of enteric coating solution pH5.5 (MAE 30 DP): weighing MAE 30DP, adding triethyl citrate, and stirring for 10 minutes; and (3) adding talcum powder into purified water, stirring for 10 minutes, emulsifying for 10 minutes, cooling, adding into the solution of MAE 30DP, continuously stirring for 1 hour, and finally sieving the solution.
Ammonia was used only for the preparation of both S100 and L100 solutions.
Referring specifically to FIG. 1, in this experimental example, rats were divided into a normal group (physiological saline), a model group (physiological saline), a material+semaglutin-pH 5.5 administration group (N-P+GLP-1 RA-pH5.5, wherein the amount of semaglutin administered was 1000. Mu.g/kg), a material+semaglutin-pH 6.0 administration group (N-P+GLP-1 RA-pH6.0, wherein the amount of semaglutin administered was 1000. Mu.g/kg), and a material+semaglutin-pH 7.0 administration group (N-P+GLP-1 RA-pH7.0, wherein the amount of semaglutin administered was 1000. Mu.g/kg). Except normal rats, the other rats were all type ii diabetic rats, and each group was given gavage.
The products obtained in examples 1, 2 and 3 were simultaneously aligned, as can be seen from the figures: compared with a model group, under the condition of coating with different pH values, the change value of the blood sugar of rats with intervention of the hollow carbon nano pump medicine loaded with the semaglutin is larger, and the blood sugar of rats is obviously inhibited. And the inhibition degree of blood sugar has obvious relation with different pH coatings: the hollow carbonaceous nano-pump drug loaded with the semaglutin has the most obvious blood sugar inhibition effect on rats under the pH7.0 coating, and the pH is 6.0 and the pH is 5.5.
FIG. 2 is a graph showing the distribution of N-P-1 particle diameters; FIG. 3 is a graph showing the distribution of N-P-2 particle size;
the hollow carbon nano pump material is modified by adopting a mode of adjusting reactants. See in particular figures 6, 7, 8. Specifically, in the step 1, an anionic surfactant can be oleic acid or sodium oleate, a nonionic surfactant can be tween 80, tween 20 or P123, and water is mixed to obtain a solution I; the carbohydrate is mixed with water to give solution II. Wherein the mass ratio of the anionic surfactant to the nonionic surfactant to the water in the solution I is 1:20-1:350;
the ratio of carbohydrate to water in solution II is in the range of 1:10-1:15; the mass ratio of anionic surfactant to nonionic surfactant is in the range of 1:1 to 1:15.
Wherein, P123 is a polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer.
Further, when the size of the material is regulated, the anionic surfactant is oleic acid, the nonionic surfactant is P123, and the mass ratio of oleic acid to P123 is 1:1.2, and the volume is small.
The anionic surfactant is sodium oleate, the nonionic surfactant is tween 80, the mass ratio of the sodium oleate to the tween 80 is 1:1.2, and the volume is small; 1:3, medium volume; 1:12.4, large volume.
When the texture of the material is regulated, preparing a flexible material, wherein the anionic surfactant is sodium oleate, the nonionic surfactant is tween 20, and the mass ratio of the sodium oleate to the tween 20 is 1:10; when the surface characteristics of the material are regulated, the anionic surfactant is sodium oleate, the nonionic surfactant is Tween 80 and P123, and the sodium oleate: tween 80: the mass ratio of P123 is 1:0.6:0.6, and the material with rough surface can be prepared. When materials with different neck lengths are prepared, the anionic surfactant is sodium oleate, the nonionic surfactant is P123, and the mass ratio of the sodium oleate to the P123 is 1:1.2.
And 2, fully mixing the two solutions obtained in the step 1, and carrying out hydrothermal reaction at the temperature of 150-220 ℃. Wherein the reaction time is 21h-60h.
And step 3, washing the solution system obtained in the step 2 with water. The reaction solution system was suction filtered with a 0.45 μm aqueous filter, and washed with deionized water 4 times. And drying the pumped and filtered substance at 50-100 ℃ for 2-24 hours to obtain the hollow carbonaceous nano pump material.
Preferably, the drying temperature in the step 3 is 50-60 ℃ and the drying time is 4-5h.
Young's modulus of the hollow carbonaceous nano pump ranges from 1MPa to 10GPa. The specific surface area of the hollow carbonaceous nano pump is between 50 and 600m 2 /g。
And 4, dispersing the material obtained in the step 3 in an organic solvent, and carrying out ultrasonic treatment and centrifugation to obtain the hollow carbonaceous nano pump material with the modified structure. Wherein the organic solvent is ethanol solution with concentration of 50% -100%, the ultrasonic time is 60-120min, and the ultrasonic temperature is 20-40 ℃; the centrifugal speed is 4500-9500rpm/min, and the centrifugal time is 3-10min; the drying temperature is 50-100 ℃ and the drying time is 2-24h.
Further, the organic solvent is 50% ethanol solution, the ultrasonic time is 60min, the temperature is 40 ℃, the centrifugal speed is 7500rpm/min, the time is 5min, and the drying is carried out for 4h at 60 ℃. The ratio of the hollow carbonaceous nano pump to the 50% ethanol solution is 1g:250mL.
Step 5, dispersing the material obtained in the step 4 in a drug solution, wherein the material is in a range of-1 kg/cm to 1.2kg/cm 2 And loading the medicine for 1-8 hours under the conditions of 100-300rpm/min under the pressure environment, and drying to obtain the hollow carbonaceous nano pump material loaded with the medicine.
Preferably, the vacuum pressure value is-1 kg/cm 2 The adsorption time is 5-8h, and the stirring speed is 200rpm/min.
And 6, placing the material loaded with the medicine in the step 5 into a dialysis bag with the molecular weight cutoff MW 10000-14000 for release, wherein the release speed is 75-150rpm/min, the release temperature is 20-37 ℃, and the release time is 1-24h.
Fig. 6 shows the use of sodium oleate: tween 80 mass ratio is 1:1.2, 160 ℃, and the small-volume hollow carbon nano pump material prepared by reacting for 21 hours is shown in an SEM schematic diagram; by adjusting sodium oleate: the shape and the size of the hollow carbonaceous nano pump material can be effectively regulated and controlled by the mass ratio of Tween 80/Tween 20.
Fig. 7 is a graph using sodium oleate: tween 80: the SEM image of the hollow carbonaceous nano pump material with rough surface prepared by the reaction for 21h at 160 ℃ with the mass ratio of P123 of 1:0.6:0.6 shows the surface roughness of the hollow carbonaceous nano pump.
Fig. 8 is a graph using sodium oleate: the SEM image of the flexible hollow carbon nano pump material prepared by tween 20 with the mass ratio of 1:12 and 160 ℃ and the reaction time of 21 hours shows that the hollow carbon nano pump material is soft.
Fig. 4-10 are further illustrations and limitations of material morphologies. The foregoing is merely illustrative of preferred embodiments of the present invention, and the scope of the present invention is not limited thereto, but any changes or substitutions that would occur to those skilled in the art within the scope of the present invention are intended to be included in the scope of the present invention.
Claims (10)
1. The oral medicine structure based on the hollow carbonaceous nano pump is characterized by comprising a core pill, a plurality of hollow carrier bodies adhered to the outer wall of the core pill, medicines filled in the hollow carrier bodies and an enteric coating layer coated outside the hollow carrier bodies.
2. The hollow carbonaceous nano-pump based oral drug structure of claim 1, wherein the hollow carrier body is a hollow carbonaceous nano-pump, and the preparation method thereof is as follows: after the first solution and the second solution are subjected to hydrothermal reaction, dispersing the first solution and the second solution by an organic solvent to obtain the aqueous dispersion liquid; the first solution is obtained by mixing an anionic surfactant, a nonionic surfactant and water, and the second solution is obtained by mixing a carbohydrate and water.
3. The hollow carbonaceous nano-pump based oral drug structure of claim 1, wherein the core pellet comprises the following components in parts by weight: 30 parts of hollow carbonaceous nano pump filled with medicine, 90 parts of caprylic/capric acid polyethylene glycol glyceride, 55 parts of silicon dioxide, 200 parts of microcrystalline cellulose, 75 parts of lactose monohydrate, 25 parts of croscarmellose sodium and 25 parts of hydroxypropyl methylcellulose.
4. The hollow carbonaceous nano-pump based oral drug structure of claim 1, wherein the enteric coating layer comprises the following components in parts by weight: 75.8 parts of copolymer, 37.9 parts of talcum powder, 11.4 parts of triethyl citrate and water.
5. The hollow carbonaceous nano-pump based oral drug structure of claim 4, further comprising 1mol/L aqueous ammonia.
6. The hollow carbonaceous nano-pump based oral drug structure of claim 1, wherein the copolymer is a methacrylic acid and methyl methacrylate copolymer, or an aqueous methacrylic acid and ethyl acrylate copolymer dispersion.
7. The hollow carbonaceous nano-pump based oral drug structure of claim 1, wherein the mass ratio of methacrylic acid to methyl methacrylate is 1:2.
8. The hollow carbonaceous nano-pump based oral drug structure of claim 1, wherein the mass ratio of methacrylic acid to methyl methacrylate is 1:1.
9. A method for the preparation of an oral pharmaceutical structure based on a hollow carbonaceous nano-pump according to any one of claims 1-8, comprising the steps of:
step one, weighing part of caprylic/capric acid polyethylene glycol glyceride and silicon dioxide, and uniformly mixing and stirring for later use;
step two, weighing hydroxypropyl methylcellulose, adding the hydroxypropyl methylcellulose into purified water, stirring and dissolving, and then adding caprylic/capric acid polyethylene glycol glyceride, stirring uniformly to obtain an adhesive;
step three, weighing the hollow carbonaceous nano pump filled with the medicine and the microcrystalline cellulose according to an equal progressive mode, uniformly mixing, then adding the mixed material in the step 1, and then adding lactose monohydrate and croscarmellose sodium, uniformly mixing and stirring;
step four, adding the adhesive in the step two into the step three, and performing wet granulation to obtain a soft material;
pouring the soft material into an extruder, extruding, and screening with a screen of 0.5mm to obtain an extrudate;
step six, putting the extrudate into a rounding machine for rounding;
step seven, after rounding, putting the mixture into a vacuum drying oven for drying, and obtaining plain pills after drying;
step eight, preparing an enteric coating;
and step nine, putting the dried plain pills into a fluidized bed, and performing bottom spraying coating to obtain the oral medicine of the hollow carbonaceous nano pump. The temperature is controlled between 30 and 35 ℃, and the weight gain of the coating is about 25 percent.
10. The method of claim 9, wherein the method of step eight is: preparation of enteric coating liquid with pH7.0, namely S100: weighing S100, adding the mixture into purified water, stirring for 5-10 minutes, slowly dripping 1mol/L ammonia water solution, stirring for 1 hour, adding triethyl citrate, and stirring for 1 hour; and (3) adding talcum powder into the purified water, stirring for 10 minutes, emulsifying for 10 minutes, cooling, adding into the solution of S100, continuously stirring for 10 minutes, and finally sieving the solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311064002.2A CN117137881A (en) | 2023-08-23 | 2023-08-23 | Oral medicine structure based on hollow carbonaceous nano pump and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311064002.2A CN117137881A (en) | 2023-08-23 | 2023-08-23 | Oral medicine structure based on hollow carbonaceous nano pump and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117137881A true CN117137881A (en) | 2023-12-01 |
Family
ID=88885932
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311064002.2A Pending CN117137881A (en) | 2023-08-23 | 2023-08-23 | Oral medicine structure based on hollow carbonaceous nano pump and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117137881A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104706640A (en) * | 2015-02-10 | 2015-06-17 | 哈尔滨珍宝制药有限公司 | Irbesartan-containing pharmaceutical composition and preparing process thereof |
| CN106082160A (en) * | 2016-06-02 | 2016-11-09 | 浙江大学 | Preparation method of Carbon Hollow material and products thereof |
| CN108524941A (en) * | 2018-04-08 | 2018-09-14 | 哈尔滨工业大学 | A kind of enzyme driving ampuliform nano-motor and preparation method thereof |
| CN109626356A (en) * | 2019-02-15 | 2019-04-16 | 东北林业大学 | A kind of hollow porous nano charcoal of low cytotoxicity and preparation method thereof |
| CN113104836A (en) * | 2021-03-04 | 2021-07-13 | 上海大学 | Carbon nano material with flask structure and preparation method thereof |
| CN114948898A (en) * | 2022-03-28 | 2022-08-30 | 深圳善康医药科技股份有限公司 | Naltrexone hydrochloride pellet for treating tumors and preparation method thereof |
-
2023
- 2023-08-23 CN CN202311064002.2A patent/CN117137881A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104706640A (en) * | 2015-02-10 | 2015-06-17 | 哈尔滨珍宝制药有限公司 | Irbesartan-containing pharmaceutical composition and preparing process thereof |
| CN106082160A (en) * | 2016-06-02 | 2016-11-09 | 浙江大学 | Preparation method of Carbon Hollow material and products thereof |
| CN108524941A (en) * | 2018-04-08 | 2018-09-14 | 哈尔滨工业大学 | A kind of enzyme driving ampuliform nano-motor and preparation method thereof |
| CN109626356A (en) * | 2019-02-15 | 2019-04-16 | 东北林业大学 | A kind of hollow porous nano charcoal of low cytotoxicity and preparation method thereof |
| CN113104836A (en) * | 2021-03-04 | 2021-07-13 | 上海大学 | Carbon nano material with flask structure and preparation method thereof |
| CN114948898A (en) * | 2022-03-28 | 2022-08-30 | 深圳善康医药科技股份有限公司 | Naltrexone hydrochloride pellet for treating tumors and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| CHUNHONG CHEN等: "Asymmetric Flasklike Hollow Carbonaceous Nanoparticles Fabricated by the Synergistic Interaction between Soft Template and Biomass", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 139, no. 7, pages 2657 - 2663 * |
| TIANYU GAO等: "Self-Adaptive Flask-like Nanomotors Based on Fe3O4 Nanoparticles to a Physiological pH.", NANOMATERIALS (BASEL), vol. 12, no. 12, pages 2049 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI224967B (en) | Oral sustained-release preparation of fasudil hydrochloride | |
| CN102105139B (en) | Process for the preparation of gastroretentive dosage forms | |
| CN1295467A (en) | Biphasic controlled release delivery system for high solubility pharmaceuticals and method | |
| WO2020113812A1 (en) | Nadh-containing biological high-molecular-weight nanosphere, preparation method for same, and applications thereof | |
| CN105617362B (en) | A novel insulin-phospholipid-chitosan self-assembled microparticle carrier and its preparation | |
| CN103784396B (en) | Ibuprofen oral micropill xerogel and preparation method thereof | |
| CN106474129A (en) | Composition of XiLin or its pharmaceutically acceptable salt and pharmaceutic adjuvant and preparation method thereof won by a kind of handkerchief | |
| CN117137881A (en) | Oral medicine structure based on hollow carbonaceous nano pump and preparation method thereof | |
| CN101744788A (en) | Omeprazole enteric coated tablet and preparation method thereof | |
| CN114557982A (en) | Perampanel electrospun fiber oral instant film agent and preparation method thereof | |
| TWI311488B (en) | ||
| CN106421807A (en) | A kind of preparation method of insulin-loaded carboxymethyl chitosan/chitosan nano preparation | |
| CN118267374A (en) | Composition and preparation for regulating blood lipid level and preparation method | |
| CN117122578A (en) | JPH 203-loaded modified polymer nanoparticle, and preparation method and application thereof | |
| Ge et al. | Development of self-emulsifying nanoplatform as anti-diabetic sulfonylurea carrier for oral diabetes therapy | |
| CN108042495B (en) | A kind of Glipizide lipid nano particle solid pharmaceutical preparation | |
| CN114522150B (en) | Preparation method and application of a pH-sensitive plant microcapsule nano-extruder | |
| CN103271907B (en) | Oral medicine composition consisting of berberine and melbine, and preparation method thereof | |
| CN106822907A (en) | A kind of two-phase delivery formulations containing racecadotril and preparation method thereof | |
| WO2019237446A1 (en) | Trimetazidine sustained-release tablet and preparation method therefor | |
| CN113133987B (en) | Preparation method of ultra-long circulating nano-carrier for tenib drugs | |
| CN1543943A (en) | Oral silymarin sustained-release preparation and preparation method thereof | |
| CN102579358B (en) | A kind of drug sustained-release pellet and preparation method thereof | |
| WO2002060448A1 (en) | Medicinal composition | |
| CN107823178B (en) | Niflumic acid colon targeted preparation for treating irritable bowel syndrome and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |