CN1686143A - Hendecanoic acid testosterone self emulsified soft capsule composition and its preparation method - Google Patents
Hendecanoic acid testosterone self emulsified soft capsule composition and its preparation method Download PDFInfo
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- CN1686143A CN1686143A CN 200510049550 CN200510049550A CN1686143A CN 1686143 A CN1686143 A CN 1686143A CN 200510049550 CN200510049550 CN 200510049550 CN 200510049550 A CN200510049550 A CN 200510049550A CN 1686143 A CN1686143 A CN 1686143A
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- 239000007901 soft capsule Substances 0.000 title claims abstract description 25
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 title claims description 36
- 239000000203 mixture Substances 0.000 title claims description 22
- 238000002360 preparation method Methods 0.000 title claims description 19
- 229960003604 testosterone Drugs 0.000 title claims description 18
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 title claims description 17
- 229960000746 testosterone undecanoate Drugs 0.000 claims abstract description 35
- UDSFVOAUHKGBEK-CNQKSJKFSA-N testosterone undecanoate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCCCCCC)[C@@]1(C)CC2 UDSFVOAUHKGBEK-CNQKSJKFSA-N 0.000 claims abstract description 35
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 24
- 238000003756 stirring Methods 0.000 claims abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- 239000000839 emulsion Substances 0.000 claims description 25
- -1 Tween-85 Polymers 0.000 claims description 20
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 17
- 239000002245 particle Substances 0.000 claims description 17
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical class CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 16
- 239000003921 oil Substances 0.000 claims description 15
- 235000019198 oils Nutrition 0.000 claims description 15
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 12
- 239000008158 vegetable oil Substances 0.000 claims description 12
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 10
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 10
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 10
- 238000012377 drug delivery Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 6
- 229920000053 polysorbate 80 Polymers 0.000 claims description 6
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 4
- 239000002736 nonionic surfactant Substances 0.000 claims 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000005456 glyceride group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 210000002784 stomach Anatomy 0.000 abstract description 3
- 239000002131 composite material Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 26
- 239000003814 drug Substances 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 15
- 125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 14
- 238000013019 agitation Methods 0.000 description 12
- 239000011521 glass Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 239000000470 constituent Substances 0.000 description 10
- 230000001804 emulsifying effect Effects 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000007957 coemulsifier Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 230000002269 spontaneous effect Effects 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000001828 Gelatine Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004945 emulsification Methods 0.000 description 3
- 210000004051 gastric juice Anatomy 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 239000004530 micro-emulsion Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000007764 o/w emulsion Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010040453 Sex chromosomal abnormalities Diseases 0.000 description 1
- AOQIVBOEDICQDB-KNWHVVHCSA-N [(5s,8r,9s,10s,13s,14s,17s)-10,13-dimethyl-3-oxo-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl] undecanoate Chemical compound C([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CCCCCCCCCC)[C@@]2(C)CC1 AOQIVBOEDICQDB-KNWHVVHCSA-N 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
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- 229940125396 insulin Drugs 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
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- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
A self-emulsifying composite softgel of testosterone undecanoate is proportionally prepared from testosterone undecanoate, oil phase and emulsifier through dissolving testosterone undecanoate in oil phase, adding oil phase, stirring, and loading in softcapsule. It can be automatically emulsified in stomach for high curative effect.
Description
Technical field
The invention belongs to pharmaceutical field, relate to oral soft capsule preparation and preparation method, relate in particular to the self emulsified soft capsule composition and the preparation method of testosterone undecanoate.
Background technology
(testosterone undecanoate TU) is the derivant of testosterone to testosterone undecanoate.Stronger androgen and assimilation are arranged, and androgen can obviously promote protein synthesis (assimilation) and reduce aminoacid and decompose (disassimilation), makes muscle growth, weight increase, and hemopoietic function of bone marrow potentiation is still arranged in addition.Main dosage form is injection and soft capsule at present, clinical male sexual disorder and the infertility of being used for, man's sex chromosomal abnormality sexual function disfunction (Crane Fitow syndrome) and aplastic anemia etc.Testosterone undecanoate is very easily dissolving in chloroform or benzene, dissolves in ethanol, and is molten in the vegetable oil part omitted, insoluble in water.Because the poorly water-soluble of medicine can not disperse homogeneous in water, so oral administration can not well pass through gastrointestinal absorption.The soft capsule of oral TU is arranged in the market, but it is reported, this oral TU only 2% enters blood circulation with prototype TU and 5 α-dihydro testosterone undecanoate through lymphsystem after the metabolism in vivo, and bioavailability is lower.
Charman had reported self-emulsifying drug delivery system (Self-EmulsifingDrug Deliver System on Pharm.Res in 1992, SEDDS), this system is with the carrier of oil phase as hydrophobic drug, medicine is dissolved in behind the oil phase according to a certain percentage and emulsifier, add co-emulsifier in case of necessity, form homogeneous, transparent solution.This stability of solution is good, in case mixed with water, under ambient temperature (being often referred to 37 ℃ of body temperature), only need the just spontaneous formation oil-in-water emulsion of energy of gentle agitation, particle diameter is generally below 5 μ m.In this uniform solution, hydrophobic drug is dissolved in oil phase, and oral water back and in the gastric juice mixes, spontaneous formation Emulsion under gastric peristalsis, medicine is dispersed in the oil-in-water droplet, is scattered in gastrointestinal tract fast and is absorbed, thereby improved bioavailability of medicament.Because of the emulsion process of this solution is carried out under one's belt automatically, so be known as self-emulsifying drug delivery system (SEDDS).Along with the increase of emulsifying agent consumption, the particle diameter of emulsion droplet further reduces, and can form transparent or translucent microemulsion.The product of oral self emulsifying and self-emulsifying microemulsion system is relative less, successfully come out but the NeoralTM microemulsion concentrated soft of ciclosporin A in 1994 is capsular, make self-emulsifying drug delivery system (SEDDS) and self-micro-emulsification medicine-releasing system (SMEDDS) more and more be subject to people's attention as the research of pharmaceutical carrier.SEDDS has vast potential for future development as a kind of novel drug-supplying system that can improve the hydrophobic drug bioavailability.
SEDDS is usually designed to the capsule of single dose, and generally speaking, solid SEDDS can have bigger content of dispersion, but is difficult to determine the state of medicine in solid SEDDS, so generally adopt the self-emulsifying drug delivery systems of homogeneous liquid form.The key for preparing this self-emulsifying drug delivery system is that the oil phase in the system and emulsifier type and ratio are optimized, and filters out homogeneous, the compositions that self-emulsifying ability is strong.The oil phase that SEDDS requires is wanted and can even under the cryopreservation condition, also do not had medicine and separate out with the medicine of less consumption dissolving recipe quantity, and by the emulsifying agent institute emulsifying in the prescription, oil phase has vegetable oil, fatty acid, triglyceride etc. easily.Long-chain at present commonly used and medium-chain different saturation triglyceride design the self emulsifying dosage form.The general non-ionic surface active agent that adopts high HLB value of emulsifying agent, the strongly hydrophilic of high HLB value emulsifying agent are to form the oil-in-water emulsion droplet immediately and self emulsifying liquid spreads necessary in aqueous environment.Different types of polyoxyethylene oleate, Sorbitan ethoxylate are the most frequently used emulsifying agents, and general content is at 30%-60%.Sometimes only having emulsifying agent can't make the solution quick emulsification, so also need add co-emulsifier, generally is alcohol, ethylene glycol, the propylene glycol of long-chain, the derivant of polyglycereol, as ethanol, isopropyl alcohol, glycerol, Polyethylene Glycol etc.In containing the SEDDS soft capsule of co-emulsifier, pure and mild other volatile co-emulsifier gelatine capsule shell of moving into may cause the precipitation of fat-soluble medicine, thereby influence the curative effect of medicine.
Self-emulsifying drug delivery systems is estimated its quality with self emulsifying efficient usually.Mainly comprise self emulsifying speed and the emulsifying size of back emulsion droplet fully.Particle diameter that it is generally acknowledged emulsion droplet is main factor, directly influences the absorption of medicine.Thick emulsion formulation to two kinds of ciclosporin As studies show that emulsion droplet is more little, and the absorption of medicine is good more.Bioavailability improves.Suitable self emulsifying prescription can be optimized selection by phasor.
SEDDS has been used for various kinds of drug at present, as local anesthetic (lignocaine); Antibiotic (norfloxacin); Hormone (Progesterone); Immunosuppressant (ciclosporin); Vitamin (VA, VE); Enzyme and insulin, Somat, calcitonin etc.So far also be not prepared into self-emulsifying drug delivery system's report about testosterone undecanoate.
Summary of the invention
An object of the present invention is to provide Hendecanoic acid testosterone self emulsified soft capsule composition, the shared mass ratio of each component is: testosterene undecannoata is 0.1-20%, and oil phase is 7-80%, and emulsifying agent is 17-90%.
The oil phase that Hendecanoic acid testosterone self emulsified soft capsule composition provided by the invention is used, comprise vegetable oil, middle long chain triglyceride (containing 8-10 C), used emulsifying agent is a non-ionic surface active agent, comprising Tween-80, Tween-85, Tween-20, polyoxyethylene hydrogenated Oleum Ricini, generally is blended emulsifying agent.The emulsifying agent that the present invention uses is not limited to above institute and gives an actual example.
The mass ratio of two kinds of emulsifying agents is 1 in the blended emulsifier: 0.3-5, the mass ratio of oil phase and emulsifying agent are 1: 0.25-10.
Another object of the present invention provides the preparation method of Hendecanoic acid testosterone self emulsified soft capsule composition: testosterone undecanoate is dissolved in the oil phase, in proportion emulsifier is formed the solution of homogeneous, self-emulsifying drug delivery systems, do not contain co-emulsifier in the native system, can overcome the pure constituents gelatine capsule shell of moving into and cause the shortcoming of drug precipitation, increased the stability of compositions, getting this solution mixes with the hydrochloric acid solution of 0.1M, just can form the Emulsion of oil-in-water type by the stirring of gentleness, the particle diameter of emulsion droplet below 5 μ m, the soft capsule of packing into.This Emulsion mixes with water in the gastric juice after oral, can spontaneous formation emulsion under the wriggling of stomach.
Different with commercially available testosterone undecanoate soft capsule (not containing surfactant) release mechanism, capsule composition provided by the invention, after the capsule shells dissolving, medicinal liquid mixes with water in the gastric juice, spontaneous formation emulsion under the wriggling of stomach, the particle diameter of emulsion droplet is at 5 μ m, even can reach nanoscale, the infiltration rate and the degree of medicine be can improve greatly, thereby bioavailability and curative effect improved.Hendecanoic acid testosterone self emulsified soft capsule composition provided by the invention does not contain co-emulsifier, can overcome the pure constituents gelatine capsule shell of moving into and cause the shortcoming of drug precipitation, has increased the stability of compositions.Hendecanoic acid testosterone self emulsified soft capsule preparation process thereof of the present invention is simple, with low cost, and stable performance is convenient to store and transportation.Automatic emulsified under one's belt after it is oral, thus bioavailability and curative effect can be improved.
The specific embodiment
The invention will be further described below with reference to specific embodiment, and these examples only are used for illustration purpose, and are not used in the restriction scope of the invention.
Example 1
A kind of mass percent (%) of Hendecanoic acid testosterone self emulsified soft capsule composition
Testosterone undecanoate 10.7
Decanoyl/octanoyl glycerides 41.7
Tween-80 31.4
Tween-20 16.2
Preparation: get testosterone undecanoate and be dissolved in the decanoyl/octanoyl glycerides, the solution that adds Tween-80, Tween-20 formation homogeneous, with solution and 37 ℃ of 0.1mol/L mixed in hydrochloric acid of 20ml, use the Glass rod gentle agitation, promptly get and have blue opalescent translucent Emulsion, particle diameter is about 3 μ m.
Example 2
The another kind of mass percent (%) of Hendecanoic acid testosterone self emulsified soft capsule composition
Testosterone undecanoate 7.0
Decanoyl/octanoyl glycerides 27.0
Tween-80 28.0
Tween-20 41.0
Preparation: get testosterone undecanoate and be dissolved in the decanoyl/octanoyl glycerides, the solution that adds Tween-80, Tween-20 formation homogeneous, with solution and 37 ℃ of 0.1mol/L mixed in hydrochloric acid of 20ml, use the Glass rod gentle agitation, promptly get and have blue opalescent translucent Emulsion, particle diameter is about 3 μ m.
Example 3
The third mass percent (%) of Hendecanoic acid testosterone self emulsified soft capsule composition
Testosterone undecanoate 10.0
Decanoyl/octanoyl glycerides 41.2
Tween-85 24.4
Tween-20 24.4
Preparation: get testosterone undecanoate and be dissolved in the vegetable oil, add the solution of Tween-85 and Tween-20 formation homogeneous,, use the Glass rod gentle agitation solution and 37 ℃ of 0.1mol/L mixed in hydrochloric acid of 20ml, obtained blue opalescent transparence emulsion, the particle diameter major part is below 2 μ m.
Example 4: constituent mass percentage ratio (%)
Testosterone undecanoate 7.0
Decanoyl/octanoyl glycerides 25.0
Tween-85 51.0
Tween-20 13.0
Preparation: get testosterone undecanoate and be dissolved in the vegetable oil, add the solution of Tween-85 and Tween-20 formation homogeneous,, use the Glass rod gentle agitation solution and 37 ℃ of 0.1mol/L mixed in hydrochloric acid of 20ml, obtained blue opalescent transparence emulsion, the particle diameter major part is about 3 μ m.
Example 5: constituent mass percentage ratio (%)
Testosterone undecanoate 13.0
Decanoyl/octanoyl glycerides 69.0
Polyoxyethylene hydrogenated Oleum Ricini 7.0
Tween-85 21.0
Preparation: get testosterone undecanoate and be dissolved in the decanoyl/octanoyl glycerides, the solution that adds polyoxyethylene hydrogenated Oleum Ricini, Tween-85 formation homogeneous, with solution and 37 ℃ of 0.1mol/L mixed in hydrochloric acid of 20ml, use the Glass rod gentle agitation, promptly get and have blue opalescent translucent Emulsion, particle diameter is about 3 μ m.
Example 6: constituent mass percentage ratio (%)
Testosterone undecanoate 15.0
Decanoyl/octanoyl glycerides 68.0
Polyoxyethylene hydrogenated Oleum Ricini 5.0
Tween-85 12.0
Preparation: get testosterone undecanoate and be dissolved in the decanoyl/octanoyl glycerides, the medicinal liquid that adds polyoxyethylene hydrogenated Oleum Ricini, Tween-85 formation homogeneous, the 0.1mol/L hydrochloric acid solution of medicinal liquid with 37 ℃ of 20ml mixed, use the Glass rod gentle agitation, promptly get and have blue opalescent translucent Emulsion.Particle diameter is at 2-10 μ m, mostly about 5 μ m.
Example 7: constituent mass percentage ratio (%)
Testosterone undecanoate 6.0
Decanoyl/octanoyl glycerides 33.0
Polyoxyethylene hydrogenated Oleum Ricini 33.0
Tween-85 28.0
Preparation: get testosterone undecanoate and be dissolved in the decanoyl/octanoyl glycerides, add the solution of polyoxyethylene hydrogenated Oleum Ricini, Tween-85 formation homogeneous,, use the Glass rod gentle agitation solution and 37 ℃ of 0.1mol/L mixed in hydrochloric acid of 20ml, promptly get and have white emulsion, particle diameter is about 5 μ m.
Example 8: constituent mass percentage ratio (%)
Testosterone undecanoate 5.0
Decanoyl/octanoyl glycerides 24.0
Polyoxyethylene hydrogenated Oleum Ricini 12.0
Tween-85 59.0
Preparation: get testosterone undecanoate and be dissolved in the decanoyl/octanoyl glycerides, add the solution of polyoxyethylene hydrogenated Oleum Ricini, Tween-85 formation homogeneous,, use the Glass rod gentle agitation solution and 37 ℃ of 0.1mol/L mixed in hydrochloric acid of 20ml, promptly get white emulsion, particle diameter is about 5 μ m.
Example 9: constituent mass percentage ratio (%)
Testosterone undecanoate 15.0
Vegetable oil 38.5
Polyoxyethylene hydrogenated Oleum Ricini 13.2
Tween-85 33.3
Preparation: get testosterone undecanoate and be dissolved in the vegetable oil, the medicinal liquid that adds polyoxyethylene hydrogenated Oleum Ricini, Tween-85 formation homogeneous, the 0.1mol/L hydrochloric acid solution of medicinal liquid with 37 ℃ of 20ml mixed, use the Glass rod gentle agitation, promptly get and have blue opalescent transparence Emulsion.Particle diameter is about 2 μ m.
Example 10: constituent mass percentage ratio (%)
Testosterone undecanoate 1.0
Vegetable oil 9.0
Polyoxyethylene hydrogenated Oleum Ricini 25.0
Tween-85 65.0
Preparation: get testosterone undecanoate and be dissolved in the vegetable oil, the medicinal liquid that adds polyoxyethylene hydrogenated Oleum Ricini, Tween-85 formation homogeneous, the 0.1mol/L hydrochloric acid solution of medicinal liquid with 37 ℃ of 20ml mixed, use the Glass rod gentle agitation, promptly get and have blue opalescent transparence Emulsion.Particle diameter is about 2 μ m.
Example 11: constituent mass percentage ratio (%)
Testosterone undecanoate 10.0
Vegetable oil 30.0
Polyoxyethylene hydrogenated Oleum Ricini 40.0
Tween-85 20.0
Preparation: get testosterone undecanoate and be dissolved in the vegetable oil, add the medicinal liquid of polyoxyethylene hydrogenated Oleum Ricini, Tween-85 formation homogeneous, the 0.1mol/L hydrochloric acid solution of medicinal liquid with 37 ℃ of 20ml mixed, use the Glass rod gentle agitation, promptly get white emulsion, particle diameter is about 5 μ m.
Claims (7)
1. Hendecanoic acid testosterone self emulsified soft capsule composition, form by testosterone undecanoate, oil phase, emulsifying agent, it is characterized in that: emulsifying agent is a nonionic surfactant, the shared mass ratio of each component is that testosterone undecanoate is 0.1-20%, oil phase is 7-80%, and nonionic surfactant is 17-90%.
2. Hendecanoic acid testosterone self emulsified soft capsule composition according to claim 1 is characterized in that: oil phase is selected from vegetable oil, contain in the middle long chain triglyceride fatty glyceride of 8-10 carbon any.
3. Hendecanoic acid testosterone self emulsified soft capsule composition according to claim 1 is characterized in that: nonionic surfactant is selected from Tween-80, Tween-85, Tween-20, the polyoxyethylene hydrogenated Oleum Ricini any.
4. according to the arbitrary described Hendecanoic acid testosterone self emulsified soft capsule composition of claim 1-3, it is characterized in that: compositions selects blended nonionic surfactant to make emulsifying agent.
5. by the arbitrary described Hendecanoic acid testosterone self emulsified soft capsule composition of claim 1-4, it is characterized in that: the mass ratio of oil phase and emulsifying agent is 1: 0.25-10.
6. by the arbitrary described Hendecanoic acid testosterone self emulsified soft capsule composition of claim 1-4, it is characterized in that: the mass ratio of two kinds of emulsifying agents is 1 in the blended emulsifier: 0.3-5.
7. the preparation method of the described Hendecanoic acid testosterone self emulsified soft capsule composition of claim 1-6: testosterone undecanoate is dissolved in the oil phase, in proportion emulsifier is formed the solution of homogeneous, self-emulsifying drug delivery systems, getting this solution mixes with the hydrochloric acid solution of 0.1mol/L, just can form the Emulsion of oil-in-water type by the stirring of gentleness, the particle diameter of emulsion droplet is below 5 μ m.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101480399B (en) * | 2008-09-25 | 2011-10-05 | 宋博 | Application of andrusol in preparing medicament for treating asthenospermia |
| CN103830245A (en) * | 2010-04-12 | 2014-06-04 | 克劳拉斯医疗有限公司 | Oral testosterone ester formulation and application of same in preparation of drug used for treating testosterone deficiency |
| US10543219B2 (en) | 2010-04-12 | 2020-01-28 | Clarus Therapeutics, Inc. | Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same |
| US11179402B2 (en) | 2005-04-15 | 2021-11-23 | Clarus Therapeutics, Inc. | Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same |
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2005
- 2005-04-04 CN CN 200510049550 patent/CN1686143A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11179402B2 (en) | 2005-04-15 | 2021-11-23 | Clarus Therapeutics, Inc. | Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same |
| US11331325B2 (en) | 2005-04-15 | 2022-05-17 | Clarus Therapeutics, Inc. | Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same |
| CN101480399B (en) * | 2008-09-25 | 2011-10-05 | 宋博 | Application of andrusol in preparing medicament for treating asthenospermia |
| CN103830245A (en) * | 2010-04-12 | 2014-06-04 | 克劳拉斯医疗有限公司 | Oral testosterone ester formulation and application of same in preparation of drug used for treating testosterone deficiency |
| US10543219B2 (en) | 2010-04-12 | 2020-01-28 | Clarus Therapeutics, Inc. | Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same |
| US10617696B2 (en) | 2010-04-12 | 2020-04-14 | Clarus Therapeutics, Inc. | Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same |
| US11179403B2 (en) | 2010-04-12 | 2021-11-23 | Clarus Therapeutics, Inc. | Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same |
| US11426416B2 (en) | 2010-04-12 | 2022-08-30 | Clarus Therapeutics, Inc. | Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same |
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