CN104688835A - Rhubarb charcoal temperature-sensitive gel as well as preparation method and application thereof - Google Patents
Rhubarb charcoal temperature-sensitive gel as well as preparation method and application thereof Download PDFInfo
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- CN104688835A CN104688835A CN201510032262.0A CN201510032262A CN104688835A CN 104688835 A CN104688835 A CN 104688835A CN 201510032262 A CN201510032262 A CN 201510032262A CN 104688835 A CN104688835 A CN 104688835A
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- rhizoma rhei
- charred radix
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Abstract
The invention discloses a rhubarb charcoal temperature-sensitive gel, as well as a preparation method and application thereof. The rhubarb charcoal temperature-sensitive gel comprises rhubarb charcoal, P407 and P188; the granularity of the rhubarb charcoal is 15-45 mu m. The rhubarb charcoal temperature-sensitive gel is liquid when refrigerated in a fridge; when the gel is delivered to the gastric mucosa, the gel becomes a solid at the temperature of 35 DEG C because the P407 and the P188 are temperature-sensitive materials. The double effects of the physical hemostasis and the medicine hemostasis can be played when the gel reaches the surface of the gastric mucosa, so that the bleeding can be rapidly stopped.
Description
Technical field
The invention belongs to biopharmacy technical field, specifically, the present invention relates to a kind of charred Radix Et Rhizoma Rhei thermosensitive hydrogel and its production and use.
Background technology
Thermosensitive hydrogel is as a kind of novel form of administration; have the advantage of solution and ordinary gel agent concurrently, there is medication convenient, healthy, be beneficial to the dispersion of medicine in affected part, absorb and maintain drug level within a certain period of time; to the mechanical protection effect of mucosa, patient's compliance high.
Poloxamer (poloxamer) is comparatively typical temperature-responsive polymer material, being recorded, being used widely at art of pharmacy because having good biocompatibility by multiple medicines allusion quotation.Can gel phase transition temperature be the primary feature of thermosensitive hydrogel, be directly connected to patient's compliance and the therapeutic effect of preparation in suitable time inherent agents area generation gelling.
But, about being that the charred Radix Et Rhizoma Rhei thermosensitive hydrogel of main matrix has no report with poloxamer.
Summary of the invention
The present invention is intended to solve one of technical problem in correlation technique at least to a certain extent.For this reason, one object of the present invention is to propose a kind of charred Radix Et Rhizoma Rhei thermosensitive hydrogel and its production and use, this charred Radix Et Rhizoma Rhei thermosensitive hydrogel is liquid when refrigerator storage cold preservation, when administration arrives gastric mucosa, because P407, P188 are temperature sensing material, temperature becomes solid reaching 35 degree of rapid gels, make medicine just play the double effects of physics hemostasis and drug hemostasis in gastric mucosa surface, thus reach the object of quick-acting haemostatic powder.
In one aspect of the invention, the present invention proposes a kind of charred Radix Et Rhizoma Rhei thermosensitive hydrogel, comprising:
Charred Radix Et Rhizoma Rhei, the granularity of described charred Radix Et Rhizoma Rhei is 15 ~ 45 μm;
P407; And
P188。
Liquid according to the charred Radix Et Rhizoma Rhei thermosensitive hydrogel of the embodiment of the present invention when refrigerator storage cold preservation, when administration arrives gastric mucosa, due to P407, P188 is temperature sensing material, temperature becomes solid reaching 35 degree of rapid gels, make medicine just play the double effects of physics hemostasis and drug hemostasis in gastric mucosa surface, thus reach the object of quick-acting haemostatic powder.
In addition, charred Radix Et Rhizoma Rhei thermosensitive hydrogel according to the above embodiment of the present invention can also have following additional technical characteristic:
In some embodiments of the invention, described charred Radix Et Rhizoma Rhei thermosensitive hydrogel comprises: the P188 of 2wt%; The P407 of 14 ~ 15wt%; And the charred Radix Et Rhizoma Rhei of 5 ~ 10wt%.
In some embodiments of the invention, described charred Radix Et Rhizoma Rhei thermosensitive hydrogel comprises: the P188 of 2wt%; The P407 of 15wt%; And the charred Radix Et Rhizoma Rhei of 8wt%.
In second of the present invention, the present invention proposes a kind of method preparing charred Radix Et Rhizoma Rhei thermosensitive hydrogel recited above, comprise and carrying out according to following ratio:
Get distilled water 70.0mL in 150mL conical flask;
Get F127 15.0g, F68 2.0g, be scattered in distilled water surface, in 4 DEG C of stored refrigerated 24h after bottle sealing, make completely swelling; And
Along with stirring adds charred Radix Et Rhizoma Rhei 8.0g, add sodium benzoate 0.25g, ethyl hydroxybenzoate 0.25g, adds water to 100g, stirs, to obtain described gel.
Liquid according to the method gained charred Radix Et Rhizoma Rhei thermosensitive hydrogel preparing charred Radix Et Rhizoma Rhei thermosensitive hydrogel of the embodiment of the present invention when refrigerator storage cold preservation, when administration arrives gastric mucosa, due to P407, P188 is temperature sensing material, temperature becomes solid reaching 35 degree of rapid gels, make medicine just play the double effects of physics hemostasis and drug hemostasis in gastric mucosa surface, thus reach the object of quick-acting haemostatic powder.
In 3rd of the present invention, the present invention proposes a kind of gel recited above and preparing the purposes in medicine, described medicine is used for hemostasis.
In addition, charred Radix Et Rhizoma Rhei thermosensitive hydrogel according to the above embodiment of the present invention can also have following additional technical characteristic preparing the purposes in medicine:
In some embodiments of the invention, described medicine is used for the treatment of Peptic Ulcer.
Additional aspect of the present invention and advantage will part provide in the following description, and part will become obvious from the following description, or be recognized by practice of the present invention.
Detailed description of the invention
Be described below in detail embodiments of the invention, embodiment described below is exemplary, is intended to for explaining the present invention, and can not be interpreted as limitation of the present invention.
In one aspect of the invention, the present invention proposes a kind of charred Radix Et Rhizoma Rhei thermosensitive hydrogel.According to embodiments of the invention, this gel comprises charred Radix Et Rhizoma Rhei, P407 and P188.Inventor finds, this gel is by arranging in pairs or groups charred Radix Et Rhizoma Rhei and P407 and P188, this medicine is made to be liquid when refrigerator storage cold preservation, when administration arrives gastric mucosa, because P407, P188 are temperature sensing material, temperature becomes solid reaching 35 degree of rapid gels, make medicine just play the double effects of physics hemostasis and drug hemostasis in gastric mucosa surface, thus reach the object of quick-acting haemostatic powder.
It should be noted that: P407 is poloxamer188 (Poloxamer 407, Pluronic lF127, F127, German BASF), P188 is PLURONICS F87 (Poloxamer 188, Pluronic l F68, F68, German BASF).
According to embodiments of the invention, in charred Radix Et Rhizoma Rhei thermosensitive hydrogel charred Radix Et Rhizoma Rhei granularity and be not particularly limited, according to a particular embodiment of the invention, the granularity of charred Radix Et Rhizoma Rhei can be 15 ~ 45 μm.Inventor finds, if charred Radix Et Rhizoma Rhei granularity is excessive, the sedimentation of gained medicine is too fast, makes drug distribution uneven, causes clinical administration dosage to be forbidden; And undersized, pulverizing difficulty is large, cost is high, thus, adopts particle size range of the present invention to meet clinical therapeutic efficacy needs, and meets modern pharmaceutical level.
According to embodiments of the invention, charred Radix Et Rhizoma Rhei thermosensitive hydrogel can comprise the charred Radix Et Rhizoma Rhei of the P188 of 2wt%, the P407 of 14 ~ 15wt% and 5 ~ 10wt%.Inventor finds, if P407 content is lower than 14%, make gained gel phase transition temperature more than 40 DEG C, add P188 again, phase transition temperature is higher, do not reach clinical practice requirement, and more than P407 content higher than 15wt%, phase transition temperature is lower than 24 DEG C, although P188 can be added improve phase transition temperature, but add P407 simultaneously, the consumption of P188, and the P188 of 2wt%, the P407 of 14 ~ 15% can use less adjuvant, make phase transition temperature a little more than 35 DEG C that require, make phase transition temperature lower than 35 DEG C after the charred Radix Et Rhizoma Rhei of dosing 5 ~ 10wt%, and make viscosity, other indexs of mobility all reach Clinical practice requirement.
According to a particular embodiment of the invention, charred Radix Et Rhizoma Rhei thermosensitive hydrogel can comprise the charred Radix Et Rhizoma Rhei of P407 and 8wt% of P188,15wt% of 2wt%.Thus, the Thermo-sensitive to body temperature of charred Radix Et Rhizoma Rhei thermosensitive hydrogel can be improved further, make medicine just become solid mutually rapidly in arrival gastric mucosa surface, play the double effects of physics hemostasis and drug hemostasis, reach the object of quick-acting haemostatic powder.
In second of the present invention, the present invention proposes a kind of method preparing charred Radix Et Rhizoma Rhei thermosensitive hydrogel.According to embodiments of the invention, the method comprises: get distilled water 70.0mL in 150mL conical flask; Get F127 15.0g, F68 2.0g, be scattered in distilled water surface, in 4 DEG C of stored refrigerated 24h after bottle sealing, make completely swelling; And add charred Radix Et Rhizoma Rhei 8.0g along with stirring, add sodium benzoate 0.25g, ethyl hydroxybenzoate 0.25g, adds water to 100g, stirs, thus can obtain gel.Inventor finds, the method is by arranging in pairs or groups charred Radix Et Rhizoma Rhei and P407 and P188, gained medicine is made to be liquid when refrigerator storage cold preservation, when administration arrives gastric mucosa, due to P407, P188 is temperature sensing material, temperature becomes solid reaching 35 degree of rapid gels, medicine is made just to play the double effects of physics hemostasis and drug hemostasis in gastric mucosa surface, thus reach the object of quick-acting haemostatic powder, and do not need special installation, method simple, be applicable to the large production of factory, be applicable to workshop, hospital's limited production yet.
In 3rd of the present invention, the present invention proposes a kind of charred Radix Et Rhizoma Rhei thermosensitive hydrogel and preparing the purposes in medicine.According to embodiments of the invention, this medicine may be used for hemostasis.According to a particular embodiment of the invention, this medicine may be used for treating Peptic Ulcer, concrete, belongs to Ia, Ib person by Forrest typing.
Below with reference to specific embodiment, present invention is described, it should be noted that, these embodiments are only descriptive, and do not limit the present invention in any way.
Experimental example
1, instrument and material
BP211D electronic balance (German sartorius); Electronic balance (being accurate to 0.01); Thermometer (being accurate to 0.1 DEG C of German testo); Water-bath; Magnetic stirring apparatus.
P407 is poloxamer188 (Poloxamer 407, Pluronic lF127, F127, German BASF), P188 is PLURONICS F87 (Poloxamer 188, Pluronic l F68, F68, German BASF); Micron rhubarb charcoal (lot number 130515,130520,130605); Sodium benzoate, ethyl hydroxybenzoate are medicinal, and water is purified water, and other reagent are analytical pure.
2, method and result
2.1 evaluation indexes and operational approach
2.1.1 evaluation index
Phase transition temperature is the primary feature of thermosensitive hydrogel, and can gel be directly connected to patient's compliance and the therapeutic effect of preparation in suitable time inherent agents area generation gelling.Therefore this research prescription screening is using phase transition temperature, transformation time as evaluation index.
2.1.2 phase transition temperature assay method
Getting test gels 1.0mL is laid on bottom 10mL conical flask, bottleneck sealed membrane seals, put it in water bath, insert precision thermometer (accurate to 0.1 DEG C, thermometer lower end is immersed in test gels completely), keep water-bath to continue slowly to heat up (heating rate: 0.2 DEG C/min), manual shallow decline conical flask, temperature when not flowing with gel is defined as phase transition temperature.
2.2 prescription screening
2.2.1 P407 is used alone prerun
Precision pipettes distilled water 5.0mL in 10mL conical flask, gets P407 appropriate, accurately weighed, be scattered in distilled water surface, in 4 DEG C of stored refrigerated 24h after bottle sealing, make completely swelling, obtain the P407 solution that concentration is 14 ~ 20wt%, measure phase transition temperature according to the method described above.
Result shows: use P407 separately, and concentration is lower than 14wt%, and phase transition temperature is more than 40 DEG C, and along with the rising of concentration, phase transition temperature reduces gradually, and when concentration is 15 ~ 18wt%, phase transition temperature is 31 ~ 24 DEG C.Therefore emphasis is to this concentration range, other substrate are coordinated to do further research.
2.2.2 the phase transition temperature of P407 and P188 different ratio mixing measures
Get P407, P188 different ratio, measure gelation temperature as stated above, result is as shown in table 1.
The phase transition temperature of table 1 P407, P188 variable concentrations proportioning
Conclusion: as shown in Table 1, along with the increase of P407 concentration, phase transition temperature reduces gradually; P407 concentration is lower than 14%, and phase transition temperature, more than 50 DEG C, obviously can not be suitable for clinical research, and increase P188 concentration, phase transition temperature raises gradually.
2.2.3 dosing is on the impact of phase transition temperature
Get P407, P188 different ratio respectively, add 5wt%, 10wt% charred Radix Et Rhizoma Rhei, then measure gelation temperature and transformation time as stated above, test result is as shown in table 2.
Table 2 charred Radix Et Rhizoma Rhei is on the impact of phase transition temperature
Conclusion: from table 2 data, adding charred Radix Et Rhizoma Rhei effectively can reduce phase transition temperature, and charred Radix Et Rhizoma Rhei ratio is larger, and phase transition temperature amount of decrease is also larger.
2.2.4 according to single factor exploration result, orthogonal design L9 is selected
3 4table, is fixed on 15wt% by P407, investigates the impact of P188 and chemical feeding quantity.
According to table 3 formula preparation thermosensitive hydrogel, adopt said method to measure phase transition temperature and the gelling time of thermosensitive hydrogel, result is as shown in table 4.
Table 3 factor level table
Table 4 orthonormal design of experiments result
According to clinical requirement, selected optimum phase transition temperature is 35 DEG C, secondly clinical consideration charred Radix Et Rhizoma Rhei dosage is comparatively large as well only has 1, No. 5 closest to 35 DEG C in table, and No. 5 No. 1, charred Radix Et Rhizoma Rhei dose ratios are large, therefore, according to above experimental result, F127 is 15wt%, and F68 is 2wt%, when charred Radix Et Rhizoma Rhei content is 8wt%, the effect of gained charred Radix Et Rhizoma Rhei thermosensitive hydrogel is optimum.
2.3 charred Radix Et Rhizoma Rhei thermosensitive hydrogel preparation technologies
Precision pipettes distilled water 70.0mL in 150mL conical flask, gets F127 15.0g, F68 2.0g, be scattered in distilled water surface, in 4 DEG C of stored refrigerated 24h after bottle sealing, make completely swelling, under stirring, slowly add charred Radix Et Rhizoma Rhei 8.0g, add sodium benzoate 0.25g, ethyl hydroxybenzoate 0.25g, adds water to 100g, stirs, 4 DEG C of cold preservations, to obtain final product.
In the description of this description, specific features, structure, material or feature that the description of reference term " embodiment ", " some embodiments ", " example ", " concrete example " or " some examples " etc. means to describe in conjunction with this embodiment or example are contained at least one embodiment of the present invention or example.In this manual, to the schematic representation of above-mentioned term not must for be identical embodiment or example.And the specific features of description, structure, material or feature can combine in one or more embodiment in office or example in an appropriate manner.In addition, when not conflicting, the feature of the different embodiment described in this description or example and different embodiment or example can carry out combining and combining by those skilled in the art.
Although illustrate and describe embodiments of the invention above, be understandable that, above-described embodiment is exemplary, can not be interpreted as limitation of the present invention, and those of ordinary skill in the art can change above-described embodiment within the scope of the invention, revises, replace and modification.
Claims (6)
1. a charred Radix Et Rhizoma Rhei thermosensitive hydrogel, is characterized in that, comprising:
Charred Radix Et Rhizoma Rhei, the granularity of described charred Radix Et Rhizoma Rhei is 15 ~ 45 μm;
P407; And
P188。
2. gel according to claim 1, is characterized in that, comprising:
The P188 of 2wt%;
The P407 of 14 ~ 15wt%; And
The charred Radix Et Rhizoma Rhei of 5 ~ 10wt%.
3. gel according to claim 1, is characterized in that, comprising:
The P188 of 2wt%;
The P407 of 15wt%; And
The charred Radix Et Rhizoma Rhei of 8wt%.
4. prepare a method for the charred Radix Et Rhizoma Rhei thermosensitive hydrogel described in any one of claims 1 to 3, it is characterized in that, comprise and carrying out according to following ratio:
Get distilled water 70.0mL in 150mL conical flask;
Get F127 15.0g, F68 2.0g, be scattered in distilled water surface, in 4 DEG C of stored refrigerated 24h after bottle sealing, make completely swelling; And
Along with stirring adds charred Radix Et Rhizoma Rhei 8.0g, add sodium benzoate 0.25g, ethyl hydroxybenzoate 0.25g, adds water to 100g, stirs, to obtain described gel.
5. the purposes in medicine prepared by the gel according to any one of claims 1 to 3, and described medicine is used for hemostasis.
6. purposes according to claim 5, is characterized in that, described medicine is used for the treatment of Peptic Ulcer.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005046438A2 (en) * | 2003-11-06 | 2005-05-26 | Pluromed, Inc. | Internal clamp for surgical procedures |
| CN1636583A (en) * | 2003-10-31 | 2005-07-13 | 成都三明药物研究所 | Medicine composition for treating women's pulvic infection and its prepn process and use |
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- 2015-01-22 CN CN201510032262.0A patent/CN104688835B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1636583A (en) * | 2003-10-31 | 2005-07-13 | 成都三明药物研究所 | Medicine composition for treating women's pulvic infection and its prepn process and use |
| WO2005046438A2 (en) * | 2003-11-06 | 2005-05-26 | Pluromed, Inc. | Internal clamp for surgical procedures |
Non-Patent Citations (2)
| Title |
|---|
| 顼佳音等: "常见温度敏感型原位凝胶载体的研究进展", 《中国实验方剂学杂志》 * |
| 顾洪安等: "HPLC法测定大黄凝胶剂中大黄素的含量", 《中成药》 * |
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