CN101658692A - Gellan gum composition, preparation method thereof and application thereof - Google Patents
Gellan gum composition, preparation method thereof and application thereof Download PDFInfo
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Abstract
The invention discloses a gellan gum composition, which is mainly prepared from a gellan gum with a high acetylation degree and/or a gellan gum with a low acetylation degree or a derivative thereof. The invention also provides a preparation method of the composition and a use method of the composition. The composition has a large amount of application serving as an injection device and/or implanted device and a medicament releasing system. The composition has the advantages that: by controlling the gelling temperature and gel elasticity of the composition, the composition can be injected in asolution state when injected to beatify so as to reduce the injection pushing resistance, and then is changed into a cohesive gel to play the corresponding role; and when prepared into a water-solublemedicinal gel, the composition can be easily and uniformly mixed by stirring in a solution state to form a gel, thereby reducing the difficulty of uniformly mixing the gel.
Description
Technical field
The present invention relates to a kind of gellan gum composition, its preparation method with and uses thereof: as beauty treatment or when medical treatment as injection and/or implant bulking of soft tissue, and the medicine-releasing system of drug molecule and other treatment agent is used.
Background technology
The perfect effort of human pursuit self never was interrupted, and the injection beautifying technique is also in continuous progress.
The injection Botulinum toxin is a better method of removing the dynamic property wrinkle at present.Botulinum toxin is a kind of strong neurovirulent protein that has, can block nerves and muscle between " signal conduction ", the loosening all muscles of excess shrinkage is unfolded.With can be used for after its dilution the human face early stage, distant wrinkle removes, as crows-feet, forehead stricture of vagina, cervical region wrinkle, the wrinkle improvement effect that injection once produces can be kept 4～6 months, reach common 1 year needs of long-term effect and inject 3～4 times.Because the extensive biological variability that exists, each human organism varies in size to this botulinal toxic reaction, and internal organs such as very thin and weak to myasthenia gravis, multiple sclerosis, the ptosis, health especially, conscience kidney have crowd Ying Shenyong such as disease, allergic constitution.
Another kind of injection beauty treatment then is to fill facial wrinkles by the mode of injection implant increase tissue mass, reaches making the depression protuberance, and face contour changes effects such as shape.This class injection beauty treatment mode has longer developing history, the updating of the material of injection and injection system.Reached at present even also be better than in some respects injecting botulinal effect, and contraindication obviously reduces.
The injection implant has selects non-biological material for use, and as early stage liquid paraffin, silica gel etc., because their seepage can cause many places inflammation in the body, and the effusion underwent operative also is difficult for thoroughly removing, and is superseded substantially now; Developed materials such as medical hydrogel of polyacrylamide, expanded PTFE afterwards, they have the better tissues compatibility, nontoxic, not by the body degraded and absorbed.This class non-biological material also can mix mutually with the better biomaterial of histocompatibility, the mixture of for example poly-methyl-propyl acid formicester and collagen protein, after in being introduced into body, biomaterial is absorbed gradually by body on the one hand, non-biological material can be used as support on the other hand, make host cell grow into gradually owing to biomaterial be absorbed the slight void of vacating gradually, thereby keep the stability of filling effect.But the direct object of injection beauty treatment is facial wrinkles, depression, the uncomfortable profile of live body, their resemblance is the result of inside and outside multiple factor interaction, change that can be in time and changing gradually, so, also will pass in time and lose its optimized feature in the injection beauty treatment scheme that a certain period is set.Non-biological material retains in vivo for a long time in addition, and the mixing with cells of growing into gradually with body together, when facial changing features need be adjusted, will be that unfavorable factor is made in the enforcement of new beauty treatment scheme, and can not thoroughly be removed.
Filled type injection beauty treatment can also be selected biomaterial for use, and such material is natural, and its advantage is that histocompatibility is good, and is promptly little with host's rejection, and can be absorbed gradually by body, do not produce lifelong effect.As far back as 1981, drugs approved by FDA used bovine collagen to be expelled to host's skin corium as filler, and to reach corresponding beauty treatment requirement, this material can be retained 6～9 months in tissue; But because this is a foreign protein matter for human body, a small amount of host's skin test allergy is arranged, even after skin test test feminine gender, still have a small amount of host allergic phenomena to occur.Occur taking from acellular collagen, the elasticin of people's corpse after a while, the glycosaminoglycan mixture is as implant, and it is similar to bovine collagen, and stickiness is bigger, and it is more lasting to act on, the anaphylaxis when not using bovine collagen; But this material source is very limited, and has the risk of propagating hepatitis B, HIV virus.Kai Fa implant was taken from host's autologous skin afterwards, through the collagen protein of preparation or cultivation generation, what have also contains from the body fibroblast, this implant non-immunogenicity, safe and effective, the fibroblast of survival still can continue to secrete collagen after 1～2 year, keep filling effect; But this concrete host is cultivated individually, obtain the mode from the body collagen protein, operation requires high, length consuming time, and the cost height is unfavorable for suitability for industrialized production and utilization.
Hyaluronic acid is the another kind of more biomaterial class implant of using.In early days the hyaluronic acid that extracts in the cockscomb has elasticity preferably, at present more sticky hyaluronic acids that adopt the microbial fermentations preparation more.Hyaluronic acid has still less inflammatory reaction, granuloma than synthetic gel when being used for human body, the production technology of microbial fermentation descends cost, and output greatly improves, and uses more extensive.When this gellike uses, make suspension earlier, inject through the fine needle hole then.If particle is too little, in host, easily be moved or engulfed, do not reach the effect that fixed point is filled; Granule is excessive or grain shape is irregular, brings difficulty then for the injection of fine needle hole, and the gel of special high-crosslinking-degree is particularly difficult in particular for the proper extension filling effect.
In addition, when the mixture of preparation gel and water soluble drug, earlier water soluble drug solution is dropped into selected gel usually, on blender, mix about 24h, lyophilization again, perhaps vacuum drying again behind the ethanol precipitation obtains exsiccant gel and water soluble drug mixture; Add an amount of Sterile Saline or buffer, mix about 24h on the blender, reach the suitable concn (Chinese patent 200480039183.2) of required gel and water soluble drug.The method complex operation of the mixture of above-mentioned preparation gel and water soluble drug, the energy consumption height, the processing time, long pharmaceutically active was easily impaired.
Therefore, need a kind of organism not had toxicity, finally can be absorbed non-animal origin, the new gel combination of the adjustable easy operating of state behind the implantable bioartificial body by body.
Gellan gum is by tetrose unit-β (1 → 3)-D-glucose β (1 → 4)-D-glucuronic acid β (1 → 4)-D-glucose α (1 → 4)-L-rhamnose, the polysaccharide that is interconnected to constitute.The inventor is by discovering: high acetyl degree gellan gum can form opaque resilient flexible glue, and low acetyl degree gellan gum forms transparent fragility gellan gum.In deionized water, add an amount of gellan gum, add heat energy and make its aquation become solution state, add an amount of cation this moment, and be cooled to proper temperature, this solution can form gel, and this gel can return back to solution state again under heat effect, and the temperature of liquefaction point is higher than the temperature of gelation point.Change gellan gum concentration and add cationic concentration, can change the temperature that forms gel.On gellan gum is formed, suitably regulate high acetyl degree gellan gum, low acetyl degree gellan gum ratio, and/or add material compatibilities such as xanthan gum, starch, the gelling properties of last formation is changed arbitrarily to elasticity by crisp.The present invention just is being based on the above-mentioned characteristic of gellan gum, and a kind of gellan gum composition with clear superiority is provided, and can be used for injecting beauty treatment, tissue filler and as the medicine-releasing system of medicine.
Summary of the invention
The objective of the invention is according to gellan gum solution under preference temperature with suitable cation sites, control the character of gel formation, a kind of gellan gum composition with height viscoelasticity is provided, said composition can be carried out such as operations such as injection, mixings with solution state, overcome direct difficulty with operations such as gel injection, mixings, in needs, finish gelation more gradually, make injected gel implant, mixing medicine-containing gel etc. become simple and easy, controlled.
Another object of the present invention provides preparation, the using method of above-mentioned gellan gum composition and is used to inject beauty treatment, tissue filler and as the purposes of the medicine-releasing system of medicine.
For achieving the above object, the present invention is by the following technical solutions:
Gellan gum composition of the present invention is that dominant shape becomes by high acetyl degree gellan gum and/or low acetyl degree gellan gum, the mass ratio of wherein high acetyl degree gellan gum and low acetyl degree gellan gum is 100: 0～0: 100, preferred 95: 15～50: 50, first-selected 80: 20 or 90: 10.
Contain biocompatible solvent in the above-mentioned composition, for example deionized water, buffer, sugar juice or analog etc. wherein comprise one or more bioactive agents in the biocompatible solvent.Described bioactive agents is cell, gene, protein, antibody, polypeptide and/or medicine etc., its Chinese medicine is not limited to local anesthetic: lignocaine, procaine, bupivacaine, cocaine, tetracaine and/or above-mentioned salt, preferred salt lidocaine hydrochloride.
Contain modified material in the above-mentioned composition, for example xanthan gum and/or starch etc.
The present composition can be used for injecting beauty treatment, tissue filler or as the medicine medicine-releasing system.
The present composition is used for the injection beauty treatment or tissue filler can be realized by following steps:
(1) takes by weighing high acetyl degree gellan gum and/or low acetyl degree gellan gum in proportion, mix, obtain mixed material;
(2) add biocompatible solvent in the material, heat and stir paramount acetyl degree gellan gum and/or the complete aquation of low acetyl degree gellan gum, obtain being in the gellan gum composition of solution state to solution state;
(3) gellan gum composition that gained is in solution state is cooled to preference temperature, and is injected into position to be filled with solution state.
The present composition is used for the injection beauty treatment or tissue filler also can be realized by following steps:
(1) takes by weighing high acetyl degree gellan gum and/or low acetyl degree gellan gum in proportion, mix, obtain mixed material;
(2) add biocompatible solvent in the material, heat and stir paramount acetyl degree gellan gum and/or the complete aquation of low acetyl degree gellan gum, add The addition of C aCl then to solution state
2(CaCl
2Can be provided cationic salt to substitute by other, preferred MgCl
2, NaCl or KCl), be stirred to fully and dissolve, obtain being in the gellan gum composition of solution state;
(3) gellan gum composition that gained is in solution state is cooled to when being higher than 0～15 ℃ of this gellan gum composition gelation point temperature (preferably 0～1 ℃), and the gel injection of solution state is gone into position to be filled.
(4) if necessary, can at this solution state gel before subcutaneous gelation, suitably adjust filling profile to reach the beauty treatment requirement by external force.
The present composition can be realized by following steps as the medicine medicine-releasing system:
(1) takes by weighing high acetyl degree gellan gum and/or low acetyl degree gellan gum in proportion, mix, obtain mixed material;
(2) add biocompatible solvent in the material, heat and stir paramount acetyl degree gellan gum and/or the complete aquation of low acetyl degree gellan gum, obtain being in the gellan gum composition of solution state to solution state; Be cooled to preference temperature then, add one or more water soluble drugs, stir to make and dissolve fully, obtain being in the gellan gum and the pharmaceutical composition of solution state;
(3) add CaCl in gellan gum and the pharmaceutical composition
2(CaCl
2Can be provided cationic salt to substitute by other, preferred MgCl
2, NaCl or KCl), be stirred to dissolving fully, replenish deionized water, standardize solution and mixing, cooling makes this gellan gum and pharmaceutical composition solution gelization.
The present composition also can be realized by following steps as the medicine medicine-releasing system:
(1) takes by weighing high acetyl degree gellan gum and/or low acetyl degree gellan gum in proportion, mix, obtain mixed material;
(2) add an amount of biocompatible solvent in the material, heat and stir paramount acetyl degree gellan gum and/or the complete aquation of low acetyl degree gellan gum, obtain being in the gellan gum composition of solution state to solution state; Add CaCl then
2(CaCl
2Can be provided cationic salt to substitute by other, preferred MgCl
2, NaCl or KCl), be stirred to dissolving fully, obtain being in the gel of solution state;
(3) gellan gum composition of cooling solution state adds one or more water soluble drugs to preference temperature, stirs to make dissolving fully, replenishes deionized water, standardize solution and mixing, and cooling forms the water soluble drug gel.
The less indication of volume that gellan gum composition of the present invention is filled for injection is selected for use and is not added cationic gellan gum composition, injects gelation under the cation sites that oozes out between the experimenter is by injection site tissue then during use with solution state; The bigger indication of volume for the injection filling, select the gellan gum composition that added cation and contained how high acetyl degree gellan gum for use, be heated to liquefaction during use, when being cooled to again a little more than the gelation point temperature, inject with solution state, temperature with local hot compress drops to the gelation point temperature that is in room temperature then, and gelation gradually.
Gellan gum composition of using for release and the preparation of water soluble drug mixture, select for use do not add or add cationic gellan gum composition all can, the former directly and water soluble drug mix and make gelation again; The latter is cooled to the suitable temperature that is higher than gelation point after heating the releasing gelation, mixes with water soluble drug again, reduces temperature then and makes gelation.
The purposes difference of the present composition, the advantage that is manifested are also different.Below further illustrate.
1. gellan gum composition of the present invention is used for the filling of tiny wrinkle
The gellan gum of getting an amount of high acetyl degree gellan gum, low acetyl degree mixes with proper proportion, can add modified material compatibilities such as xanthan gum, starch when needing.Add proper amount of deionized water again, heating, making gellan gum is that main solute aquation becomes solution state, replenishes deionized water and standardize solution then.Packing on demand, and adopt moist heat sterilization.In further embodiment, this gellan gum composition solution will be used for the filling and the reparation of tiny wrinkle.Select for use No. 30 syringe needles to adopt the injection of multiple spot ramp type, this gellan gum composition solution is injected the skin corium position that needs filling.In the interstice that gellan gum composition solution is filled, will ooze out proper C a
2+, Mg
2+, Na
+And K
+Etc. cation, make the gellan gum solution gelation gradually that is packed into, reach the effect of filling beauty treatment.
2. filling and profile that gellan gum composition of the present invention is used for dark cicatrix such as skin indenture change shape
Take by weighing the high acetyl degree gellan gum and the low acetyl degree gellan gum of proper proportion, can add modified material compatibilities such as xanthan gum, starch when needing, mix.Add appropriate amount of deionized water, it is that main solid liquefies gradually that heated and stirred makes this gellan gum, becomes liquid condition.CaCl takes a morsel
2, perhaps MgCl
2, NaCl and KCl etc. can provide cationic salt, drop into above-mentioned solution, are stirred to dissolving fully, replenish deionized water and standardize solution.By the demand packing, moist heat sterilization.In further embodiment, get the gellan gum composition heating liquefaction that presents gel state, and be transferred to environment rapidly a little more than the gelation point temperature, keep the solution state of gellan gum composition.Local heating is carried out at the position that needs larger volume to fill, and the mode of heating that can adopt hot compress etc. to be accepted by body makes the gelation point temperature of local body temperature a little more than gellan gum composition, injects filling this moment.The gellan gum composition of liquefaction will descend and progressively in subcutaneous gelation with ambient temperature.If necessary, can at gellan gum composition before subcutaneous gelation, suitably adjust filling profile to reach the beauty treatment requirement by external force.
Compare with existing injection beautifying technique, gellan gum composition of the present invention no longer is a particle suspensions when injecting, but exists with solution state, obviously reduces and injects resistance, reduces operation easier, reduces the unexpected incidence rate of operation.On the other hand, gellan gum composition of the present invention is to enter in the host with solution state, and fill and be filled the position, said composition is easy to bond on the substrate such as peripheral cell like this, progressively form the gel of suitable shape again, so not only can before gelation, have an opportunity to adjust profile, can also form gel with integral way by the external force appropriateness, promptly do not relatively move, thereby make filling effect keep more of a specified duration.On the other hand, gellan gum composition of the present invention can be by adjusting proportion of composing and compatibility situation, regulate the temperature of gelation point and the elasticity size of one-tenth's gel, make said composition satisfy the beauty treatment of constantly variation or operation requirement and the effect requirements that medical treatment is filled.
3. gellan gum composition of the present invention is used for the medicine-releasing system of water soluble drug
Get an amount of high acetyl degree gellan gum and low acetyl degree gellan gum, can add modified material compatibilities such as xanthan gum, starch in case of necessity, mix.Add deionized water in this mixture, heated and stirred makes complete aquation become solution state, and is transferred to the environment a little more than this gellan gum composition solution gel point temperature rapidly, and below operation is all operated under this temperature.Can in gellan gum composition solution, add the suitable quantity of water soluble drug under the sterilization treatment condition, and then add the CaCl that impels the gellan gum composition solution gelization
2, perhaps MgCl
2, NaCl and KCl etc. can provide cationic salt, only need the common dissolving fully that be stirred to, restock deionized water and standardize solution get final product by the demand packing.
4. gellan gum composition of the present invention is used for the medicine-releasing system of water soluble drug
Get an amount of high acetyl degree gellan gum and low acetyl degree gellan gum, can add modified material compatibilities such as xanthan gum, starch in case of necessity, mix.Add deionized water in this mixture, heated and stirred makes complete aquation become solution state, and is transferred to the environment a little more than this gellan gum composition solution gel point temperature rapidly, and below operation is all operated under this temperature.Can in gellan gum composition solution, add CaCl under the sterilization treatment condition
2, perhaps MgCl
2, NaCl and KCl etc. can provide cationic salt, add the suitable quantity of water soluble drug then, only need the common dissolving fully that be stirred to, restock deionized water and standardize solution get final product by the demand packing.
Compare with the water soluble drug mixture with the existing gel that is used for release, the uniform mixing of gel and water soluble drug needs the long-time mixing of dispersing emulsification machine, and the running cost height has also limited the preparation of gel and labile drug institute resulting mixture; Gellan gum composition of the present invention can form gel again with solution state and water soluble drug mix homogeneously easily in needs.
Therefore, gel combination superior performance of the present invention can be widely used as the gel filling agent of injection beauty treatment, and for example facial tiny wrinkle, body surface indenture, profile remodeling etc. can also be used for the mixture of convenient preparation gel and water soluble drug.
The specific embodiment
Following examples are for better explanation the present invention, never are limitations of the present invention.The preparation of embodiment 1:0.05% gellan gum composition and the application that tiny wrinkle is filled thereof
Precision takes by weighing the high acetyl degree of 40mg gellan gum, and 10mg hangs down acetyl degree gellan gum, mixes.Add deionized water 80mL in this mixture, boiling water bath heating and stirring make complete aquation become solution state, replenish deionized water then and also are settled to 100mL, prop up packing ampoule, moist heat sterilization by 1mL/.Need carry out facial tiny wrinkle and fill the experimenter of beauty treatment, after just routine, electrocardiogram, hepatic and renal function, HIV, HbsAg index detect normally through hematuria, carry out the no immunoreation of skin test (with penicillin skin test method) again.Select for use No. 30 syringe needles to adopt the injection of multiple spot ramp type, gellan gum composition solution is injected planned injection position, experimenter canthus skin corium.After the operation, note not pushing the injection site.The experimenter by the Ca in injection site tissue gap
2+, Mg
2+, Na
+And K
+Under cation sites, the gellan gum solution gelation on the throne gradually that injection is packed into reaches the effect of filling beauty treatment.Local swelling, pain can appear in the injection site, generally basic elimination in 2 weeks, and the filling effect of implant can be kept about about 6 months.
The preparation of embodiment 2:0.06% gellan gum composition and the application that the skin indenture is filled thereof
Precision takes by weighing the high acetyl degree of 54mg gellan gum, and 6mg hangs down acetyl degree gellan gum, mixes.Add deionized water 80mL in this mixture, boiling water bath heating and stirring make complete aquation become solution state.In this gellan gum solution, add CaCl
20.4440g, being stirred to dissolving fully, additional deionized water is settled to 100mL, props up packing ampoule, moist heat sterilization by 1mL/.Need carry out the experimenter that skin of face depression is filled, through hematuria just routine, electrocardiogram, hepatic and renal function, HIV, HbsAg index detect normal after, gellan gum implant skin test is accepted in preparation.The gellan gum gel ampoule that heating 1mL/ props up on boiling water bath makes this coagulant liquid change into solution state, and is transferred to 45 ℃ of freeze-day with constant temperature operation cupboards rapidly.With 1mL syringe draw solution state gellan gum, the experimenter is carried out the no immunoreation of skin test (with penicillin skin test method).Local hot compress is carried out at the skin indenture position that needs are filled then, perhaps 45 ℃ of subenvironment insulations, carries out local injection and fills, and removes thermal environment after reaching required filling extent again.The gellan gum of liquefaction descends with ambient temperature and progressively in subcutaneous gelation.Local swelling, pain can appear in the injection site, and this phenomenon is basic elimination the in 2 weeks generally, and the filling effect of implant can be kept about about 6 months.
Embodiment 3: 0.05% gellan gum composition that is used for release
Precision takes by weighing the high acetyl degree of 40mg gellan gum, and 10mg hangs down acetyl degree gellan gum, mixes.Add deionized water 50mL in this mixture, boiling water bath heating and stirring make complete aquation become solution state, are transferred to 45 ℃ of water bath heat preservations then, and below operation is all carried out under this temperature.Can in this gellan gum solution, add under the sterilization treatment condition: antitumor drug such as paclitaxel (25.00mL, 5mg/mL); Steroidal anti-inflammatory drugs solution such as dexamethasone (5.00mL, 25mg/mL) etc.Add NaCl 0.2340g then in the mixed solution of this gellan gum and medicine, be stirred to dissolving fully, the restock deionized water is settled to 100mL, props up packing by 25mL/.Form the gel that contains the uniform distribution medicine when being cooled to room temperature, in case of necessity can moist heat sterilization.
Embodiment 4: be used for the 0.05% gellan gum gel of release and the compositions of water soluble drug
Precision takes by weighing the high acetyl degree of 40mg gellan gum, and 10mg hangs down acetyl degree gellan gum, mixes.Add deionized water 50mL in this mixture, boiling water bath heating and stirring make complete aquation become solution state, are transferred to 45 ℃ of water bath heat preservations then, and below operation is all carried out under this temperature.Can in this gellan gum solution, add NaCl 0.2340g under the sterilization treatment condition, be stirred to dissolving fully; Add antitumor drug again, as paclitaxel (25.00mL, 5mg/mL), steroidal anti-inflammatory drugs solution such as dexamethasone (5.00mL, 25mg/mL) etc.And then additional deionized water is settled to 100mL, props up packing by 25mL/.Form the gel that contains the uniform distribution medicine when being cooled to room temperature, in case of necessity can moist heat sterilization.
Claims (14)
1, a kind of gellan gum composition is characterized in that: this group is that dominant shape becomes with thing by high acetyl degree gellan gum and/or low acetyl degree gellan gum.
2, the described compositions of claim 1 is characterized in that: the mass ratio of described high acetyl degree gellan gum and low acetyl degree gellan gum is 100: 0～0: 100, preferred 95: 15～50: 50, and first-selected 80: 20 or 90: 10.
3, claim 1 or 2 arbitrary described compositionss is characterized in that: contain biocompatible solvent in the said composition.
4, the described compositions of claim 3, wherein biocompatible solvent is deionized water, buffer, sugar juice or analog.
5, claim 3 or 4 arbitrary described compositionss wherein comprise one or more bioactive agents in the biocompatible solvent.
6, the described compositions of claim 5, wherein bioactive agents is cell, gene, protein, antibody, polypeptide and/or medicine, described medicine is not limited to local anesthetic: lignocaine, procaine, bupivacaine, cocaine, tetracaine and/or above-mentioned salt, preferred salt lidocaine hydrochloride.
7, claim 1 or 2 arbitrary described compositionss is characterized in that: contain modified material in the said composition, preferred xanthan gum and/or starch.
8, claim 1 or 2 arbitrary described compositionss are used to inject the purposes of beauty treatment.
9, claim 1 or 2 arbitrary described compositionss are as the purposes of medicine medicine-releasing system.
10, the described purposes of claim 8 is characterized in that: realize by following steps:
(1) takes by weighing high acetyl degree gellan gum and/or low acetyl degree gellan gum in proportion, mix, obtain mixed material;
(2) add biocompatible solvent in the material, heat and stir paramount acetyl degree gellan gum and/or the complete aquation of low acetyl degree gellan gum, obtain being in the gellan gum composition of solution state to solution state;
(3) gellan gum composition that gained is in solution state is cooled to preference temperature, and is injected into position to be filled with solution state.
11, the described purposes of claim 8 is characterized in that: realize by following steps:
(1) takes by weighing high acetyl degree gellan gum and/or low acetyl degree gellan gum in proportion, mix, obtain mixed material;
(2) add biocompatible solvent in the material, heat and stir paramount acetyl degree gellan gum and/or the complete aquation of low acetyl degree gellan gum, add The addition of C aCl then to solution state
2, be stirred to fully and dissolve, obtain being in the gellan gum composition of solution state;
(3) gellan gum composition that gained is in solution state is cooled to when being higher than 0～15 ℃ of this gellan gum composition gelation point temperature, and the gellan gum composition of solution state is injected into position to be filled.
(4) at the gellan gum composition of this solution state before subcutaneous gelation, suitably adjust filling profile by external force to reach the beauty treatment requirement.
12, the described purposes of claim 9 is characterized in that: realize by following steps:
(1) takes by weighing high acetyl degree gellan gum and/or low acetyl degree gellan gum in proportion, mix, obtain mixed material;
(2) add biocompatible solvent in the material, heat and stir paramount acetyl degree gellan gum and/or the complete aquation of low acetyl degree gellan gum, obtain being in the gellan gum composition of solution state to solution state; Be cooled to preference temperature then, add one or more water soluble drugs, stir to make and dissolve fully, obtain being in the gellan gum and the pharmaceutical composition of solution state;
(3) add CaCl in gellan gum and the pharmaceutical composition
2, be stirred to dissolving fully, replenish deionized water, standardize solution and mixing, cooling makes this gellan gum and pharmaceutical composition solution gelization.
13, the described purposes of claim 9 is characterized in that: realize by following steps:
(1) takes by weighing high acetyl degree gellan gum and/or low acetyl degree gellan gum in proportion, mix, obtain mixed material;
(2) add an amount of biocompatible solvent in the material, heat and stir paramount acetyl degree gellan gum and/or the complete aquation of low acetyl degree gellan gum, obtain being in the gellan gum composition of solution state to solution state; Add CaCl then
2, be stirred to dissolving fully, obtain being in the gellan gum composition of solution state;
(3) gel of cooling solution state adds one or more water soluble drugs to preference temperature, stirs to make dissolving fully, replenishes deionized water, standardize solution and mixing, and cooling forms the water soluble drug gel.
14, the arbitrary described method of claim 9-11, wherein said CaCl
2Can be provided cationic salt to substitute by other, preferred MgCl
2, NaCl or KCl.
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2008
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| CN110974788A (en) * | 2019-12-25 | 2020-04-10 | 广州聚明生物科技有限公司 | Medicine-carrying lacrimal duct suppository and preparation method thereof |
| CN110974788B (en) * | 2019-12-25 | 2022-06-24 | 广州聚明生物科技有限公司 | Medicine-carrying lacrimal duct suppository and preparation method thereof |
| CN113694144A (en) * | 2021-09-30 | 2021-11-26 | 南京中医药大学 | Pseudo-ginseng and bletilla striata pH responsive in-situ gel and preparation method and application thereof |
| CN113694144B (en) * | 2021-09-30 | 2023-01-10 | 南京中医药大学 | Pseudo-ginseng and bletilla striata pH responsive in-situ gel and preparation method and application thereof |
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