CN104688835B - Charred RADIX ET RHIZOMA RHEI thermo-sensitive gel and its production and use - Google Patents
Charred RADIX ET RHIZOMA RHEI thermo-sensitive gel and its production and use Download PDFInfo
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- CN104688835B CN104688835B CN201510032262.0A CN201510032262A CN104688835B CN 104688835 B CN104688835 B CN 104688835B CN 201510032262 A CN201510032262 A CN 201510032262A CN 104688835 B CN104688835 B CN 104688835B
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Abstract
The invention discloses a kind of charred RADIX ET RHIZOMA RHEI thermo-sensitive gel and its production and use, the charred RADIX ET RHIZOMA RHEI thermo-sensitive gel includes：Charred RADIX ET RHIZOMA RHEI, the granularity of the charred RADIX ET RHIZOMA RHEI is 15~45 μm；P407；And P188.The charred RADIX ET RHIZOMA RHEI thermo-sensitive gel is liquid when refrigerator storage is refrigerated, when being administered into up to gastric mucosa, due to P407, P188 is temperature sensing material, temperature is reaching that 35 degree of rapid gels are changed into solid, so that medicine just plays the double effectses of physics hemostasis and Hemostatics in gastric mucosa surface, so as to reach the purpose of quick-acting haemostatic powder.
Description
Technical field
The invention belongs to biopharmacy technical field, specifically, the present invention relates to a kind of charred RADIX ET RHIZOMA RHEI thermo-sensitive gel and its
Preparation method and purposes.
Background technology
Thermo-sensitive gel has the advantage of solution and ordinary gel agent concurrently, with medication as a kind of new form of administration
It is convenient, healthy, beneficial to medicine is in the scattered of affected part, absorption and maintains drug concentration within a certain period of time, the machinery of mucous membrane is protected
Shield is acted on, the features such as patient's compliance is high.
Poloxamer (poloxamer) is more typical temperature-responsive polymer material, because with good biology
Compatibility and recorded by many pharmacopeia, be used widely in art of pharmacy.Gel phase transition temperature is the primary spy of thermo-sensitive gel
Levy, the patient's compliance and therapeutic effect of preparation can be directly connected in occurring to be gelled in agents area in suitable time.
However, having no report about the charred RADIX ET RHIZOMA RHEI thermo-sensitive gel using poloxamer as main matrix.
The content of the invention
It is contemplated that at least solving one of technical problem in correlation technique to a certain extent.Therefore, the present invention
One purpose is to propose a kind of charred RADIX ET RHIZOMA RHEI thermo-sensitive gel and its production and use, and the charred RADIX ET RHIZOMA RHEI thermo-sensitive gel is stored up in refrigerator
Liquid when depositing refrigeration, when being administered into up to gastric mucosa, due to P407, P188 is temperature sensing material, temperature reach 35 degree it is rapid
Gel is changed into solid so that medicine just plays the double effectses of physics hemostasis and Hemostatics in gastric mucosa surface, so as to reach
The purpose of quick-acting haemostatic powder.
In one aspect of the invention, the present invention proposes a kind of charred RADIX ET RHIZOMA RHEI thermo-sensitive gel, including：
Charred RADIX ET RHIZOMA RHEI, the granularity of the charred RADIX ET RHIZOMA RHEI is 15~45 μm；
P407；And
P188。
Charred RADIX ET RHIZOMA RHEI thermo-sensitive gel according to embodiments of the present invention is liquid when refrigerator storage is refrigerated, viscous up to stomach being administered into
During film, due to P407, P188 is temperature sensing material, and temperature is reaching that 35 degree of rapid gels are changed into solid so that medicine is in gastric mucosa
Surface just plays the double effectses of physics hemostasis and Hemostatics, so as to reach the purpose of quick-acting haemostatic powder.
In addition, charred RADIX ET RHIZOMA RHEI thermo-sensitive gel according to the above embodiment of the present invention can also have technology additional as follows special
Levy：
In some embodiments of the invention, the charred RADIX ET RHIZOMA RHEI thermo-sensitive gel includes：2wt% P188；14~15wt%
P407；And 5~10wt% charred RADIX ET RHIZOMA RHEI.
In some embodiments of the invention, the charred RADIX ET RHIZOMA RHEI thermo-sensitive gel includes：2wt% P188；15wt%'s
P407；And 8wt% charred RADIX ET RHIZOMA RHEI.
In the second aspect of the invention, the present invention proposes a kind of side for preparing charred RADIX ET RHIZOMA RHEI thermo-sensitive gel recited above
Method, including carried out according to following ratio：
Distilled water 70.0mL is taken in 150mL conical flasks；
F127 15.0g, F68 2.0g are taken, distillation water surface is scattered in, bottle sealing is after 4 DEG C
Stored refrigerated 24h, makes to be swelled completely；And
As stirring adds charred RADIX ET RHIZOMA RHEI 8.0g, sodium benzoate 0.25g, ethyl hydroxy benzoate 0.25g are added, 100g is added water to, stirs
Mix uniform, to obtain the gel.
Charred RADIX ET RHIZOMA RHEI thermo-sensitive gel obtained by the method for preparing charred RADIX ET RHIZOMA RHEI thermo-sensitive gel according to embodiments of the present invention is stored up in refrigerator
Liquid when depositing refrigeration, when being administered into up to gastric mucosa, due to P407, P188 is temperature sensing material, temperature reach 35 degree it is rapid
Gel is changed into solid so that medicine just plays the double effectses of physics hemostasis and Hemostatics in gastric mucosa surface, so as to reach
The purpose of quick-acting haemostatic powder.
In the third aspect of the invention, the present invention proposes a kind of use of gel recited above in medicine is prepared
On the way, the medicine is used to stop blooding.
In addition, purposes of the charred RADIX ET RHIZOMA RHEI thermo-sensitive gel according to the above embodiment of the present invention in medicine is prepared can also have
The technical characteristic added as follows：
In some embodiments of the invention, the medicine is used to treat Peptic Ulcer.
The additional aspect and advantage of the present invention will be set forth in part in the description, and will partly become from the following description
Obtain substantially, or recognized by the practice of the present invention.
Embodiment
Embodiments of the invention are described below in detail, the embodiments described below is exemplary, it is intended to for explaining this
Invention, and be not considered as limiting the invention.
In one aspect of the invention, the present invention proposes a kind of charred RADIX ET RHIZOMA RHEI thermo-sensitive gel.Embodiments in accordance with the present invention,
The gel includes charred RADIX ET RHIZOMA RHEI, P407 and P188.Inventor has found that the gel is by the way that charred RADIX ET RHIZOMA RHEI is taken with P407 and P188
Match somebody with somebody so that the medicine is liquid when refrigerator storage is refrigerated, when being administered into up to gastric mucosa, due to P407, P188 is temperature sensitive material
Material, temperature is reaching that 35 degree of rapid gels are changed into solid so that medicine just plays physics hemostasis in gastric mucosa surface and medicine stops
The double effectses of blood, so as to reach the purpose of quick-acting haemostatic powder.
It should be noted that：P407 is poloxamer188 (Poloxamer 407, Pluronic lF127, F127, Germany
BASF), P188 is PLURONICS F87 (Poloxamer 188, Pluronic l F68, F68, German BASF).
The granularity of charred RADIX ET RHIZOMA RHEI is not particularly restricted in embodiments in accordance with the present invention, charred RADIX ET RHIZOMA RHEI thermo-sensitive gel, according to this
The specific embodiment of invention, the granularity of charred RADIX ET RHIZOMA RHEI can be 15~45 μm.Inventor has found, if charred RADIX ET RHIZOMA RHEI granularity is excessive, gained
Medicine sedimentation is too fast so that drug distribution is uneven, causes clinical administration dosage to be forbidden；And undersized, crush difficulty it is big, into
This height, thus, meets clinical therapeutic efficacy needs, and meet modern pharmaceutical level using particle size range of the present invention.
Embodiments in accordance with the present invention, charred RADIX ET RHIZOMA RHEI thermo-sensitive gel can include 2wt% P188,14~15wt% P407
With 5~10wt% charred RADIX ET RHIZOMA RHEI.Inventor has found, if P407 contents are less than 14% so that gained gel phase transition temperature is more than 40
DEG C, then adding P188, phase transition temperature is higher, does not reach clinical practice requirement, and is higher than 15wt%, phase transition temperature more than P407 contents
Less than 24 DEG C, although P188 can be added to improve phase transition temperature, but add P407, P188 consumption simultaneously, and 2wt%
P188,14~15% P407 can use less auxiliary material, phase transition temperature is slightly above 35 DEG C of requirement, and dosing 5~
Phase transition temperature is less than 35 DEG C after 10wt% charred RADIX ET RHIZOMA RHEI, and other indexs of viscosity, mobility is all reached that Clinical practice will
Ask.
According to a particular embodiment of the invention, charred RADIX ET RHIZOMA RHEI thermo-sensitive gel can include 2wt% P188,15wt% P407
With 8wt% charred RADIX ET RHIZOMA RHEI.Thus, it is possible to further improve the Thermo-sensitive to body temperature of charred RADIX ET RHIZOMA RHEI thermo-sensitive gel, make medicine
The just rapid double effectses for being mutually changed into solid, playing physics hemostasis and Hemostatics of gastric mucosa surface are reached, fast short stopping is reached
The purpose of blood.
In the second aspect of the invention, the present invention proposes a kind of method for preparing charred RADIX ET RHIZOMA RHEI thermo-sensitive gel.According to this
The embodiment of invention, this method includes：Distilled water 70.0mL is taken in 150mL conical flasks；F127 15.0g is taken, is moored
Luo Shamu P1882.0g, are scattered in distillation water surface, and bottle sealing makes to be swelled completely after 4 DEG C of stored refrigerated 24h；And with
Stirring and add charred RADIX ET RHIZOMA RHEI 8.0g, add sodium benzoate 0.25g, ethyl hydroxy benzoate 0.25g, add water to 100g, stir, so that
Gel can be obtained.Inventor has found that this method is by the way that charred RADIX ET RHIZOMA RHEI is arranged in pairs or groups with P407 and P188 so that gained medicine exists
Refrigerator storage is liquid when refrigerating, and when being administered into up to gastric mucosa, due to P407, P188 is temperature sensing material, and temperature is reaching 35
Spend rapid gel and be changed into solid so that medicine just plays the double effectses of physics hemostasis and Hemostatics in gastric mucosa surface, from
And the purpose of quick-acting haemostatic powder is reached, and do not need special installation, method simple, it is adapted to the big production of factory, also is adapted for workshop, doctor
Institute's limited production.
In the third aspect of the invention, the present invention proposes a kind of use of charred RADIX ET RHIZOMA RHEI thermo-sensitive gel in medicine is prepared
On the way.Embodiments in accordance with the present invention, the medicine can be used for hemostasis.According to a particular embodiment of the invention, the medicine can be used
In treatment Peptic Ulcer, specifically, belonging to Ia, Ib person by Forrest partings.
Below with reference to specific embodiment, present invention is described, it is necessary to which explanation, these embodiments are only description
Property, without limiting the present invention in any way.
Experimental example
1st, instrument and material
BP211D electronic balances (German sartorius)；Electronic balance (is accurate to 0.01)；Thermometer (is accurate to 0.1 DEG C
German testo)；Water-bath；Magnetic stirring apparatus.
P407 is poloxamer188 (Poloxamer 407, Pluronic lF127, F127, German BASF), and P188 is
PLURONICS F87 (Poloxamer 188, Pluronic l F68, F68, German BASF)；Micron rhubarb charcoal (lot number 130515,
130520,130605)；Sodium benzoate, ethyl hydroxy benzoate are medicinal, and water is purified water, and other reagents are pure to analyze.
2nd, method and result
2.1 evaluation indexes and operating method
2.1.1 evaluation index
Phase transition temperature is the primary feature of thermo-sensitive gel, and can gel straight in occurring gelling in agents area in suitable time
Connect the patient's compliance and therapeutic effect for being related to preparation.Therefore this research prescription screening using phase transition temperature, transformation time as
Evaluation index.
2.1.2 phase transition temperature assay method
Test gels 1.0mL is taken to be laid on 10mL conical flasks bottom, bottleneck is sealed with sealed membrane, put it into water bath,
Microthermometer (to 0.1 DEG C, thermometer lower end is completely submerged in test gels precision) is inserted, keeps water-bath to continue slow liter
Warm (heating rate：0.2 DEG C/min), manual shallow decline conical flask, temperature when not flowed with gel is defined as phase transition temperature.
2.2 prescription screening
2.2.1 prerun is used alone in P407
Precision pipettes distilled water 5.0mL in 10mL conical flasks, takes P407 appropriate, accurately weighed, is scattered in distillation water meter
Face, bottle sealing makes to be swelled completely after 4 DEG C of stored refrigerated 24h, produces the P407 solution that concentration is 14~20wt%, according to
The above method determines phase transition temperature.
As a result show：P407 is individually used, concentration is less than 14wt%, and phase transition temperature is more than 40 DEG C, with the liter of concentration
Height, phase transition temperature is gradually reduced, and when concentration is 15~18wt%, phase transition temperature is 31~24 DEG C.Therefore emphasis is to this concentration model
Enclose, coordinate other matrix are further to be studied.
2.2.2 the phase transition temperature that P407 is mixed with P188 different ratios is determined
P407, P188 different ratio are taken, gelation temperature is determined as stated above, as a result as shown in table 1.
The phase transition temperature of table 1 P407, P188 various concentrations proportioning
Conclusion：As shown in Table 1, with the increase of P407 concentration, phase transition temperature is gradually reduced；P407 concentration is less than 14%,
Phase transition temperature is more than 50 DEG C, hence it is evident that can not be applicable clinical research, increases P188 concentration, and phase transition temperature gradually rises.
2.2.3 influence of the dosing to phase transition temperature
P407, P188 different ratio, plus 5wt%, 10wt% charred RADIX ET RHIZOMA RHEI are taken respectively, and gelling temperature is then determined as stated above
Degree and transformation time, test result are as shown in table 2.
Influence of the charred RADIX ET RHIZOMA RHEI of table 2 to phase transition temperature
Conclusion：From the data in table 2, it can be seen that phase transition temperature can effectively be reduced by adding charred RADIX ET RHIZOMA RHEI, and charred RADIX ET RHIZOMA RHEI ratio is bigger,
Phase transition temperature amount of decrease is also larger.
2.2.4 according to single factor exploration result, from orthogonal design L93 4Table, 15wt% is fixed on by P407, investigates P188
With the influence of chemical feeding quantity.
Thermo-sensitive gel is prepared according to the prescription of table 3, the phase transition temperature and gelling time of thermo-sensitive gel are determined using the above method,
As a result it is as shown in table 4.
The factor level table of table 3
The orthonormal design of experiments result of table 4
According to clinical requirement, it is 35 DEG C to select optimal phase transition temperature, secondly clinical to consider that charred RADIX ET RHIZOMA RHEI dosage is larger preferably, table
In only 1, No. 5 closest to 35 DEG C, and No. 5 charred RADIX ET RHIZOMA RHEI dose ratios are No. 1 big, therefore, according to above experimental result, poloxamer
P407 is 15wt%, and F68 is 2wt%, when rheum officinale carbon content is 8wt%, the effect of gained charred RADIX ET RHIZOMA RHEI thermo-sensitive gel
It is optimal.
2.3 charred RADIX ET RHIZOMA RHEI thermo-sensitive gel preparation technologies
Precision pipettes distilled water 70.0mL in 150mL conical flasks, takes F127 15.0g, poloxamer
P1882.0g, is scattered in distillation water surface, and bottle sealing makes to be swelled completely, slowly added under stirring after 4 DEG C of stored refrigerated 24h
Enter charred RADIX ET RHIZOMA RHEI 8.0g, add sodium benzoate 0.25g, ethyl hydroxy benzoate 0.25g, add water to 100g, stir, 4 DEG C of refrigerations, i.e.,
.
In the description of this specification, reference term " one embodiment ", " some embodiments ", " example ", " specifically show
The description of example " or " some examples " etc. means to combine specific features, structure, material or the spy that the embodiment or example are described
Point is contained at least one embodiment of the present invention or example.In this manual, to the schematic representation of above-mentioned term not
Identical embodiment or example must be directed to.Moreover, specific features, structure, material or the feature of description can be with office
Combined in an appropriate manner in one or more embodiments or example.In addition, in the case of not conflicting, the skill of this area
Art personnel can be tied the not be the same as Example or the feature of example and non-be the same as Example or example described in this specification
Close and combine.
Although embodiments of the invention have been shown and described above, it is to be understood that above-described embodiment is example
Property, it is impossible to limitation of the present invention is interpreted as, one of ordinary skill in the art within the scope of the invention can be to above-mentioned
Embodiment is changed, changed, replacing and modification.
Claims (5)
1. a kind of charred RADIX ET RHIZOMA RHEI thermo-sensitive gel, it is characterised in that including：
5~10wt% charred RADIX ET RHIZOMA RHEI, the granularity of the charred RADIX ET RHIZOMA RHEI is 15~45 μm；
14~15wt% P407；And
2wt% P188.
2. gel according to claim 1, it is characterised in that including：
2wt% P188；
15wt% P407；And
8wt% charred RADIX ET RHIZOMA RHEI.
3. a kind of method of the charred RADIX ET RHIZOMA RHEI thermo-sensitive gel prepared described in any one of claim 1~2, it is characterised in that including by
Carried out according to the following steps：
Distilled water 70.0mL is taken in 150mL conical flasks；
F127 15.0g, F68 2.0g are taken, distillation water surface is scattered in, bottle sealing is cold after 4 DEG C
Hide and preserve 24h, make to be swelled completely；And
As stirring adds charred RADIX ET RHIZOMA RHEI 8.0g, sodium benzoate 0.25g, ethyl hydroxy benzoate 0.25g are added, 100g is added water to, stirring is equal
It is even, to obtain the gel.
4. purposes of the gel according to any one of claim 1~2 in medicine is prepared, the medicine is used to stop blooding.
5. purposes according to claim 4, it is characterised in that the medicine is used to treat Peptic Ulcer.
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Citations (1)
| 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 |
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|---|---|---|---|---|
| US7700086B2 (en) * | 2003-11-06 | 2010-04-20 | Pluromed, Inc. | Internal clamp for surgical procedures |
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Patent Citations (1)
| 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 |
Non-Patent Citations (2)
| Title |
|---|
| HPLC法测定大黄凝胶剂中大黄素的含量;顾洪安等;《中成药》;20011031;第23卷(第10期);第772-774页，尤其是第773页左栏第1段 * |
| 常见温度敏感型原位凝胶载体的研究进展;顼佳音等;《中国实验方剂学杂志》;20110131;第17卷(第2期);第252-257页，尤其是第252页左栏第1段至右栏第1段，第253页表1 * |
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