CN112190498B - Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof - Google Patents
Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof Download PDFInfo
- Publication number
- CN112190498B CN112190498B CN202011198623.6A CN202011198623A CN112190498B CN 112190498 B CN112190498 B CN 112190498B CN 202011198623 A CN202011198623 A CN 202011198623A CN 112190498 B CN112190498 B CN 112190498B
- Authority
- CN
- China
- Prior art keywords
- theophylline
- cyclodextrin
- water
- inclusion compound
- soluble
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/738—Cyclodextrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种具有水溶性的茶碱和环糊精包合物及其制备方法。该包合物的组份包含：茶碱、环糊精、络合剂。该方法包括：将茶碱的乙醇溶液和环糊精水溶液，混合均匀，得到混合液；将混合液旋转蒸发，除去乙醇，然后冷冻干燥处理，过筛，得到所述水溶性、高配伍性的茶碱和环糊精包合物。本发明制备得到的茶碱和环糊精包合物，相比于茶碱，改善了其水溶性，有效提高了稳定性、配伍性。本发明解决了茶碱在化妆品领域中水溶性低、配伍性差、稳定性较低等问题。另外本发明提供的制备方法工艺简单，便于操作，用时较短，适合于工业化生产。
The invention discloses a water-soluble inclusion compound of theophylline and cyclodextrin and a preparation method thereof. The components of the inclusion compound include: theophylline, cyclodextrin, and complexing agent. The method comprises: mixing the ethanol solution of theophylline and the cyclodextrin aqueous solution uniformly to obtain a mixed solution; rotating the mixed solution to remove ethanol, then freeze-drying and sieving to obtain the water-soluble and highly compatible solution. Theophylline and cyclodextrin inclusion complex. Compared with theophylline, the theophylline and the cyclodextrin inclusion compound prepared by the invention has improved water solubility and effectively improved stability and compatibility. The invention solves the problems of low water solubility, poor compatibility and low stability of theophylline in the cosmetic field. In addition, the preparation method provided by the present invention is simple in process, convenient in operation, short in time, and suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of efficacy cosmetics, in particular to a water-soluble theophylline and cyclodextrin inclusion compound and a preparation method thereof.
Background
Theophylline, as a hypoxanthine compound, is an alkaloid widely present in tea leaves. In the field of cosmetics, theophylline has the functions of removing wrinkles, efficiently repairing epidermal tissues and lightening dark circles. Therefore, theophylline has great development potential in the field of functional cosmetics.
However, theophylline has many disadvantages, which limit its development and utilization:
1. the solubility was poor. The aqueous solubility of theophylline was low at room temperature, about 8.3mg/mL, and the solubility in chloroform was about 9.1 mg/mL.
2. The compatibility is poor. The low water solubility and low fat solubility of theophylline make it less soluble in aqueous or oily phases and poorly compatible with other cosmetic materials.
The existing literature has limited research on improving the water solubility of theophylline, the compatibility of theophylline in cosmetics and the slow-release effect. The invention patent (CN201310180115.9) "preparation method of theophylline sustained release tablet" discloses a preparation method of theophylline sustained release tablet, and the preparation method can improve the sustained release effect of theophylline. However, this method also has disadvantages: the method only improves the slow release effect of theophylline, but does not improve the water solubility and compatibility of the theophylline, and limits the application of the theophylline in functional cosmetics.
Cyclodextrins are cyclic oligosaccharides composed of alpha-1, 4 glycosidically linked glucose units, usually containing 6-12D-glucopyranose unit structures, among which the more studied and widely used molecules containing 6, 7, 8 glucose units, respectively, are called alpha-cyclodextrin, beta-cyclodextrin and gamma-cyclodextrin, respectively. From the structure, the cyclodextrin molecule is in a shape of a truncated cone with a big end and a small end, and due to the arrangement sequence of the functional groups, the hydroxyl groups of the glucose unit are positioned at two edges of the truncated cone, and the hydrogen atoms on C3 and C5 are positioned in the inner cavity of the truncated cone, so that the cyclodextrin has the special properties of hydrophobic inner cavity and hydrophilic outer wall. The cyclodextrin is stable in chemical property and not easily affected by external conditions such as pH, enzyme and heat, and the hydrophobic inner cavity can provide an ideal action site to form an inclusion compound with a hydrophobic compound with a certain size and shape, so that the water solubility of the hydrophobic compound is changed, the effects of shielding, slow release, activity protection and the like can be achieved, and the application field of the cyclodextrin is expanded.
Disclosure of Invention
In order to overcome the defects of the application technology of theophylline in the field of functional cosmetics, the invention mainly aims to provide a preparation method of a water-soluble theophylline and cyclodextrin inclusion compound.
Another object of the present invention is to provide a theophylline and cyclodextrin inclusion compound having water solubility, which can improve the water solubility and compatibility of theophylline.
The invention at least achieves the above purpose through one of the following technical schemes.
The invention provides a water-soluble theophylline and cyclodextrin inclusion compound, which comprises theophylline, cyclodextrin and a complexing agent.
The invention provides a water-soluble theophylline and cyclodextrin inclusion compound, which comprises the following components in percentage by mass: 3-9% of theophylline, 75-85% of cyclodextrin and 8-15% of complexing agent.
Preferably, in the component having theophylline and cyclodextrin inclusion compounds which are water-soluble, the molar ratio of theophylline to cyclodextrin is 1: 0.25-4.
Further preferably, in the component having theophylline and cyclodextrin inclusion compounds which are water-soluble, the molar ratio of theophylline to cyclodextrin is 1: 1.
Further, the cyclodextrin is more than one of alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin and 2-hydroxyethyl-beta-cyclodextrin.
Preferably, the cyclodextrin is 2-hydroxypropyl- β -cyclodextrin.
Further, the complexing agent is more than one of Ethylene Diamine Tetraacetic Acid (EDTA), polyvinylpyrrolidone (PVP) and sodium Polyacrylate (PAAS).
The particle size of the water-soluble theophylline and cyclodextrin inclusion compound is 40-200 nm.
The method for preparing the water-soluble and high-compatibility theophylline @ cyclodextrin inclusion compound (namely the water-soluble theophylline and cyclodextrin inclusion compound) comprises the following steps:
(1) adding theophylline into anhydrous ethanol, and mixing to obtain theophylline ethanol solution;
(2) adding cyclodextrin and a complexing agent into deionized water, uniformly mixing to obtain a cyclodextrin aqueous solution, then adding the theophylline ethanol solution obtained in the step (1) under a stirring state, and stirring and mixing to obtain a mixed solution;
(3) and (3) performing rotary evaporation on the mixed solution obtained in the step (2), removing ethanol to obtain an aqueous solution of the theophylline cyclodextrin inclusion compound, and performing freeze drying treatment to obtain the water-soluble theophylline and cyclodextrin inclusion compound.
Further, in the ethanol solution of theophylline in the step (1), the concentration of the theophylline is 12.5-50 mM.
Further preferably, in the theophylline ethanol solution of step (1), the concentration of theophylline is 50 mM.
Further, in the cyclodextrin aqueous solution of the step (2), the concentration of cyclodextrin is 12.5-200 mM.
Further, in the cyclodextrin water solution in the step (2), the concentration of the complexing agent is 10-50 mM.
Further, the volume ratio of the cyclodextrin water solution to the theophylline ethanol solution in the step (2) is 1:0.25-1: 4.
Preferably, the temperature of the stirring and mixing in the step (2) is 30-60 ℃, the time of the stirring and mixing is 6-48h, and the speed of the stirring and mixing is 200-800 r/min.
Further preferably, the temperature of the stirring and mixing in the step (2) is 40 ℃, the time of the stirring and mixing is 24 hours, and the speed of the stirring and mixing is 600 r/min.
Further, the time of the freeze drying treatment in the step (3) is 12-36 h.
Compared with the prior art, the invention has the following advantages and beneficial effects:
(1) compared with theophylline, the theophylline and cyclodextrin inclusion compound with water solubility has good stability while improving the solubility;
(2) the water-soluble theophylline and cyclodextrin inclusion compound can be compounded with various functional cosmetic raw materials, and shows good compatibility;
(3) the invention provides a method for preparing the theophylline @ cyclodextrin inclusion compound by using a cyclodextrin inclusion compound preparation technology, and the method is simple in preparation process, short in time consumption and beneficial to industrial production;
(4) compared with theophylline, the water-soluble theophylline and cyclodextrin inclusion compound has good slow release property, and can slow down the release speed of the theophylline without influencing the function of the theophylline.
Drawings
FIG. 1 is a transmission electron microscope image of theophylline and cyclodextrin inclusion compounds having water solubility prepared in example 1.
FIG. 2 is a graph showing a standard concentration of the aqueous theophylline solution used in example 1.
Fig. 3 is a graph showing the slow release of theophylline and cyclodextrin inclusion compounds and theophylline with water solubility prepared in example 2.
Fig. 4 is a graph showing the slow release of theophylline and cyclodextrin inclusion compounds and theophylline with water solubility prepared in example 3.
Fig. 5 is a graph showing the slow release of theophylline and cyclodextrin inclusion compounds and theophylline with water solubility prepared in example 4.
Detailed Description
The following examples are presented to further illustrate the practice of the invention, but the practice and protection of the invention is not limited thereto. It is noted that the processes described below, if not specifically described in detail, are all realizable or understandable by those skilled in the art with reference to the prior art. The reagents or apparatus used are not indicated to the manufacturer, and are considered to be conventional products available by commercial purchase.
In the following examples, the procedure for the in vitro sustained release test of theophylline and cyclodextrin inclusion compounds having water solubility was as follows:
selecting PBS buffer solution (10mM, pH 7.4) as dispersion liquid and dialysate, respectively dispersing theophylline, theophylline with water solubility and cyclodextrin inclusion compound in the dialysate to make its concentration be 2mg/mL, placing 5mL dispersion liquid in dialysis bag (30KDa), placing in dialysate (200mL), and stirring at 37 deg.C; then, 1ml of dialysate was removed at different time points, respectively, and 1ml of fresh dialysate was replenished. Adding 3mL of acetone into the dialysate to perform rotary extraction for 5min, centrifuging (3000rpm, 5min), collecting the upper organic extract, extracting for 3 times, drying all the extracts with nitrogen, adding ethanol into the residue to dissolve and fix the volume to 10mL, measuring the theophylline concentration with an ultraviolet spectrophotometer, and calculating the cumulative release rate.
Example 1
The water-soluble theophylline and cyclodextrin inclusion compound comprises 8% of theophylline, 85% of 2-hydroxypropyl-beta-cyclodextrin and 7% of ethylenediamine tetraacetic acid in percentage by mass.
The preparation method of the water-soluble theophylline and cyclodextrin inclusion compound comprises the following steps:
accurately weighing 0.45g of theophylline, adding absolute ethyl alcohol to 50mL, and uniformly mixing to obtain a theophylline ethanol solution with the concentration of 50 mM; accurately weighing 3.85g of 2-hydroxypropyl beta-cyclodextrin and 1.0g of ethylenediamine tetraacetic acid, and adding ultrapure water to 50mL to obtain a 50mM 2-hydroxypropyl-beta-cyclodextrin aqueous solution; respectively transferring 5mL of theophylline ethanol solution and 5mL of 2-hydroxypropyl-beta-cyclodextrin aqueous solution by using a liquid transfer gun, mixing the two solutions, and stirring and reacting for 24h at the rotating speed of 600r/min under the condition of heating in a constant-temperature water bath at 40 ℃. And (3) performing rotary evaporation on the reacted solution to remove ethanol to obtain an aqueous solution of the water-soluble theophylline and cyclodextrin inclusion compound, freezing the aqueous solution at the temperature of-18 ℃ for 24 hours, performing freeze drying treatment, fully volatilizing water to obtain dried block powder, crushing the obtained block powder by using a mortar, and sieving the crushed block powder by using a 140-mesh sieve to obtain the water-soluble theophylline and cyclodextrin inclusion compound powder.
The transmission electron micrograph of the theophylline and cyclodextrin inclusion compound powder having water solubility obtained in this example is shown in FIG. 1.
The theophylline powder and the theophylline and cyclodextrin inclusion compound powder having water solubility obtained in example 1 were subjected to solubility tests, respectively, which were conducted by the following steps:
respectively adding excessive theophylline, water-soluble theophylline and cyclodextrin inclusion compound powder into 10ml of ultrapure water, performing ultrasonic treatment at 60 deg.C for 30min, filtering the suspension with needle filter, allowing the suspension to pass through water phase filtering membrane with pore diameter of 5 μm, and performing ultraviolet spectrophotometric detection on the filtrate. And substituting the obtained spectrophotometry into a theophylline standard concentration curve to calculate the concentration of the theophylline dissolved in the water. The standard concentration curve of theophylline is shown in figure 2.
The test results were as follows:
the maximum solubility of theophylline in water before encapsulation was: 7.8mg/mL, the maximum solubility in water after the formation of the water-soluble theophylline and cyclodextrin inclusion compound is 125mg/mL, and the water solubility of the water-soluble theophylline and cyclodextrin inclusion compound is improved by more than 15 times compared with the theophylline.
The theophylline and cyclodextrin inclusion compounds having water solubility obtained in example 1 were added to various cosmetic raw materials to perform compatibility tests, and the test results are shown in table 1. The test result shows that after the water-soluble theophylline and cyclodextrin inclusion compound powder is added, no difference changes occur in pH, appearance and the like of the humectant, the thickener and the preservative, and the good compatibility is proved.
TABLE 1
Example 2
The water-soluble theophylline and cyclodextrin inclusion compound comprises, by mass, 5% of theophylline, 90% of beta-cyclodextrin and 5% of sodium polyacrylate.
The preparation method of the water-soluble theophylline and cyclodextrin inclusion compound comprises the following steps:
accurately weighing 0.225g of theophylline, adding absolute ethyl alcohol to 100mL, and uniformly mixing to obtain a theophylline ethanol solution with the concentration of 12.5 mM; weighing 11.35g of beta-cyclodextrin and 0.5g of sodium polyacrylate, and adding ultrapure water to 100mL to obtain a 100mM beta-cyclodextrin aqueous solution; respectively transferring 5mL of theophylline ethanol solution and 5mL of beta-cyclodextrin aqueous solution by using a liquid transfer gun, mixing the two solutions, and stirring and reacting at the rotating speed of 500r/min for 24h under the condition of heating in a thermostatic water bath at 50 ℃. And (3) performing rotary evaporation on the solution after reaction to remove ethanol to obtain an aqueous solution of water-soluble theophylline and cyclodextrin inclusion compound, freezing at the temperature of-18 ℃ for 24 hours, performing freeze drying treatment, fully volatilizing water to obtain dried block powder, crushing the obtained block powder by using a mortar, and sieving by using a 140-mesh sieve to obtain water-soluble theophylline and cyclodextrin inclusion compound powder which is marked as theophylline @ cyclodextrin inclusion compound 2.
Fig. 3 is a graph showing the effect of the slow release of the water-soluble theophylline and cyclodextrin inclusion compound with theophylline prepared in example 2. It can be seen that the theophylline and cyclodextrin inclusion compound having water solubility prepared in example 2 has a good sustained-release effect compared to theophylline, the cumulative release rate of the theophylline and cyclodextrin inclusion compound having water solubility is only 50% of that of theophylline within one hour, and the cumulative release rate of the theophylline and cyclodextrin inclusion compound having water solubility after six hours is only about 75% of that of theophylline, indicating that the theophylline and cyclodextrin inclusion compound having water solubility prepared in example 2 has a good sustained-release effect.
Example 3
The water-soluble theophylline and cyclodextrin inclusion compound comprises the following components in percentage by mass: 5% of theophylline, 8% of 2-hydroxypropyl-beta-cyclodextrin and 15% of polyvinylpyrrolidone.
The preparation method of the water-soluble theophylline and cyclodextrin inclusion compound comprises the following steps:
accurately weighing 0.45g of theophylline, adding absolute ethyl alcohol to 100mL, and uniformly mixing to obtain a theophylline ethanol solution with the concentration of 50 mM; accurately weighing 7.673g of 2-hydroxypropyl-beta-cyclodextrin and 1.5g of polyvinylpyrrolidone, and adding ultrapure water to 100mL to obtain a 100mM beta-cyclodextrin aqueous solution; respectively transferring 5mL of theophylline ethanol solution and 5mL of 2 hydroxypropyl-beta-cyclodextrin aqueous solution by using a liquid transfer gun, mixing the two solutions, and stirring and reacting for 24h at the rotating speed of 600r/min under the condition of heating in a constant-temperature water bath at the temperature of 60 ℃. And (3) performing rotary evaporation on the solution after reaction to remove ethanol to obtain an aqueous solution of water-soluble theophylline and cyclodextrin inclusion compound, freezing at the temperature of-18 ℃ for 24 hours, performing freeze drying treatment, fully volatilizing water to obtain dried block powder, crushing the obtained block powder by using a mortar, and sieving by using a 140-mesh sieve to obtain water-soluble theophylline and cyclodextrin inclusion compound powder which is marked as theophylline @ cyclodextrin inclusion compound 3.
The theophylline and cyclodextrin inclusion compound with water solubility obtained in example 3 are added into facial mask liquid to carry out a phase stability test, which comprises the following steps:
adding water-soluble theophylline and cyclodextrin inclusion compound into the facial mask liquid according to the proportion of 1g/100mL, wherein the components and the mass percentage of the facial mask liquid are shown in Table 2;
respectively measuring the viscosity of the facial mask liquid by using a digital display viscosity machine before and after adding the theophylline and the cyclodextrin inclusion compound with water solubility;
taking 5mL of the facial mask solution containing the water-soluble theophylline and cyclodextrin inclusion compound of the example 3, centrifuging the facial mask solution in a centrifuge tube for 5min under the condition of 3000r/min, and observing whether the facial mask solution is layered or not after the centrifugation is finished;
10mL of the facial mask solution containing the water-soluble theophylline and the cyclodextrin inclusion compound prepared in example 3 was placed in a test tube at 60 ℃ and 4 ℃ for 24h, and the stability of the facial mask solution was judged by observing whether the facial mask solution precipitated or delaminated.
The test results are shown in table 3, and it can be seen that after the addition of theophylline and cyclodextrin inclusion compounds having water solubility, the mask solution did not delaminate under various condition tests, demonstrating good phase stability.
TABLE 2
TABLE 3
FIG. 4 is a graph showing the effect of the sustained release of theophylline and cyclodextrin inclusion compounds with water solubility and theophylline prepared in example 3. It can be seen that the theophylline and cyclodextrin inclusion compounds having water solubility prepared in example 3 have good sustained release effect compared to theophylline, and the cumulative release rate of the theophylline and cyclodextrin inclusion compounds having water solubility is only about 80% of the cumulative release rate of theophylline from the beginning to 6 hours after the release. The theophylline @ cyclodextrin inclusion compound prepared in this example has a certain slow release effect.
Example 4
The water-soluble theophylline and cyclodextrin inclusion compound comprises 4% of theophylline, 90% of alpha-cyclodextrin and 6% of ethylenediamine tetraacetic acid according to the mass fraction of the inclusion compound.
The preparation method of the water-soluble theophylline and cyclodextrin inclusion compound comprises the following steps:
accurately weighing 0.45g of theophylline, adding absolute ethyl alcohol to 100mL, and uniformly mixing to obtain a theophylline ethanol solution with the concentration of 50 mM; accurately measuring 19.4g of alpha-cyclodextrin and 0.6g of ethylenediamine tetraacetic acid, and adding ultrapure water to 100mL to obtain 200mM alpha-cyclodextrin aqueous solution; respectively transferring 5mL of theophylline ethanol solution and 5mL of alpha-cyclodextrin aqueous solution by using a liquid transfer gun, mixing the two solutions, and stirring and reacting at the rotating speed of 600r/min for 24h under the condition of heating in a constant-temperature water bath at the temperature of 60 ℃. And (3) performing rotary evaporation on the solution after reaction to remove ethanol to obtain an aqueous solution of water-soluble theophylline and cyclodextrin inclusion compound, freezing at the temperature of-18 ℃ for 24 hours, performing freeze drying treatment, fully volatilizing water to obtain dried block powder, crushing the obtained block powder by using a mortar, and sieving by using a 140-mesh sieve to obtain water-soluble theophylline and cyclodextrin inclusion compound powder which is marked as theophylline @ cyclodextrin inclusion compound 4.
FIG. 5 is a graph showing the effect of the sustained release of theophylline and cyclodextrin inclusion compounds with water solubility prepared in example 4 with theophylline. It can be seen that the theophylline and cyclodextrin inclusion compound having water solubility prepared in example 4 has good slow release effect compared to theophylline, the cumulative release rate of the theophylline and cyclodextrin inclusion compound having water solubility is only 40% of the cumulative release rate of theophylline within the first 0.5h, and the cumulative release rate of the theophylline and cyclodextrin inclusion compound having water solubility after 6h is also only about 75% of theophylline, which shows that the theophylline and cyclodextrin inclusion compound having water solubility in this example has good slow release effect.
The above examples are only preferred embodiments of the present invention, which are intended to be illustrative and not limiting, and those skilled in the art should understand that they can make various changes, substitutions and alterations without departing from the spirit and scope of the invention.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011198623.6A CN112190498B (en) | 2020-10-31 | 2020-10-31 | Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011198623.6A CN112190498B (en) | 2020-10-31 | 2020-10-31 | Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112190498A CN112190498A (en) | 2021-01-08 |
| CN112190498B true CN112190498B (en) | 2022-03-25 |
Family
ID=74010671
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011198623.6A Active CN112190498B (en) | 2020-10-31 | 2020-10-31 | Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112190498B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113842366B (en) * | 2021-10-29 | 2023-04-25 | 海南全星制药有限公司 | Doxofylline for injection and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994023697A1 (en) * | 1993-04-22 | 1994-10-27 | Depotech Corporation | Cyclodextrin liposomes encapsulating pharmacologic compounds and methods for their use |
| CN1424112A (en) * | 2002-12-17 | 2003-06-18 | 上海医药工业研究院 | Water soluble dressing for insoluble medicines and preparation thereof |
| CN109010312A (en) * | 2017-11-11 | 2018-12-18 | 刘丽 | A kind of preparation method of sustained-release theophylline preparation |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2808691B1 (en) * | 2000-05-12 | 2005-06-24 | Coletica | CYCLODEXTRINS SUBSTITUTED PREFERENTIALLY ON THEIR PRIMARY SURFACE BY ACID OR AMINE FUNCTIONS |
| CA2495084C (en) * | 2002-09-20 | 2013-02-19 | The Procter & Gamble Company | Striped liquid personal cleansing compositions containing a cleansing phase and a separate benefit phase |
| EP1771149A1 (en) * | 2004-07-23 | 2007-04-11 | The Procter and Gamble Company | Skin care composition containing a flavonoid and vitamin b3 |
| EP1998788A4 (en) * | 2006-03-01 | 2011-08-03 | Ruey J Yu | Composition and method for topical treatment of tar-responsive dermatological disorders |
| CN101919803A (en) * | 2010-07-16 | 2010-12-22 | 钟术光 | A kind of controlled release preparation |
| BR102012009317B1 (en) * | 2012-04-20 | 2022-05-31 | Universidade Federal De Minas Gerais - Ufmg | Process of preparation of inclusion compounds involving cyclodextrins and drugs, using a continuous flow system |
| CN103239419B (en) * | 2013-05-15 | 2016-01-20 | 瑞阳制药有限公司 | The preparation method of Theo-Dur |
-
2020
- 2020-10-31 CN CN202011198623.6A patent/CN112190498B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994023697A1 (en) * | 1993-04-22 | 1994-10-27 | Depotech Corporation | Cyclodextrin liposomes encapsulating pharmacologic compounds and methods for their use |
| CN1424112A (en) * | 2002-12-17 | 2003-06-18 | 上海医药工业研究院 | Water soluble dressing for insoluble medicines and preparation thereof |
| CN109010312A (en) * | 2017-11-11 | 2018-12-18 | 刘丽 | A kind of preparation method of sustained-release theophylline preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112190498A (en) | 2021-01-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sun et al. | Self-assembled supermolecular hydrogel based on hydroxyethyl cellulose: Formation, in vitro release and bacteriostasis application | |
| CN107936266B (en) | Cellulose/black phosphorus nanosheet composite hydrogel and preparation method thereof | |
| Lin et al. | Effect of polysaccharide nanocrystals on structure, properties, and drug release kinetics of alginate-based microspheres | |
| Filipović-Grčić et al. | Chitosan microspheres with hydrocortisone and hydrocortisone–hydroxypropyl-β-cyclodextrin inclusion complex | |
| CN103087334B (en) | Method for preparing composite hydrogel of sodium alginate and artemisia desertorum seed gum | |
| KR101905937B1 (en) | Anthocyanidin complex | |
| CN112190498B (en) | Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof | |
| Wang et al. | Formation of composite hydrogel of carboxymethyl konjac glucomannan/gelatin for sustained release of EGCG | |
| CN105055372A (en) | Method for preparing carboxymethyl konjac glucomannan nano drug carrying microspheres | |
| WO2018038055A1 (en) | Method for producing dry product of dispersible bacterial cellulose and method for producing bacterial cellulose dispersion | |
| CN113637188B (en) | Chitosan microsphere and preparation method thereof | |
| CN116211839B (en) | Curcumin drug-loading system and preparation method thereof | |
| CN102920652A (en) | Propolis and chitosan periodontal slow-release thermo-sensitive in-situ gel and preparation method thereof | |
| US6884885B2 (en) | Production of cyclodextrin complexes | |
| CN110078941B (en) | Modified nano-hydroxyapatite supermolecule composite hydrogel and preparation method thereof | |
| CN106279723B (en) | A kind of preparation method of hydroxyethyl cellulose cyclodextrin hydrogel cage | |
| CN102153678B (en) | Preparation method of hyperbranched poly(beta-cyclodextrin) containing azide group | |
| CN105200557A (en) | Preparation method of cellulose and chitosan hybrid fiber | |
| Zhou et al. | Facile construction of pectin-based hesperidin microcapsules: solubilization, stability, loading process, and release mechanism | |
| CN104558665A (en) | Surface-modified poly-dopamine sphere subjected to ring-opening polymerization of caprolactone and preparation method of poly-dopamine sphere compound | |
| CN106822917B (en) | Acrylate functionalized bridged bond mesoporous carrier material and preparation method thereof | |
| CN106474485A (en) | A kind of voltage-stimuli responsive type intelligent nano container and preparation method thereof | |
| CN112495351A (en) | Preparation method of amino modified halloysite reinforced hydrogel | |
| CN106177988B (en) | A kind of preparation method of isoquercitin inclusion compound | |
| JP2010106068A (en) | New chemical modification method for polysaccharide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |