CN114306207A

CN114306207A - Oral administration method taking lollipop as carrier

Info

Publication number: CN114306207A
Application number: CN202111683704.XA
Authority: CN
Inventors: 基斯·肯德里克; 徐丹; 李琴; 赵伟华
Original assignee: University of Electronic Science and Technology of China
Current assignee: University of Electronic Science and Technology of China
Priority date: 2021-12-30
Filing date: 2021-12-30
Publication date: 2022-04-12

Abstract

The invention discloses an oral administration method of oxytocin, a non-peptide agonist thereof and/or an antagonistic regulator thereof by taking lollipop as a carrier, which is used for regulating social cognition and/or related behaviors of human subjects and improving symptoms of autism and emotional disorders, and particularly solves the problems of incomplete absorption, high secondary administration failure rate, low treatment effect and serious psychological conflict of children in the existing nasal spray administration mode of children with autism spectrum disorders at present. Effectively improve the social reactivity level of children.

Description

Oral administration method taking lollipop as carrier

The invention relates to an oral administration method taking saccharides as carriers, in particular to an oral administration method taking lollipop as a carrier for oxytocin, a non-peptide agonist thereof and/or an antagonistic modulator thereof, a preparation method of the lollipop containing the oxytocin, the non-peptide agonist thereof and/or the antagonistic modulator thereof, and a lollipop carrier and a preparation method thereof.

Background

As an early onset pervasive developmental Disorder, patients with Autism Spectrum Disorder (ASD) have a deficiency in social interaction, whose major features include difficulty in developing and maintaining social relationships, language retardation, repeatedly stereotypic behavioral manifestations, and significant limitations in activity interest. Although no specific medicine can treat autism spectrum disorder at present, a large number of researches prove that oxytocin can effectively improve the symptom severity of ASD patients, improve the responsiveness to social stimuli, and be more likely to establish social connections, and earlier screen children at risk of ASD for early intervention treatment, the earlier screening children at risk of ASD are more likely to recover the social functions of the children, and the children are better integrated into social activities, so that the ASD children are treated by intervention treatment with oxytocin have great clinical value.

The current basic and clinical researches mainly use a nasal spray oxytocin mode for administration, but in practice, it is found that both normally developing children and ASD children have resistance to the nasal spray mode in different degrees, nasal mucosa rupture and nosebleed are easy to occur after the nasal spray, and the discomfort causes the situations of low matching degree and high shedding rate of the children in a multi-trial nasal spray oxytocin experiment, particularly ASD children are easy to cry, cry and resist and the like; on the other hand, the nasal cavity of children is narrow, the absorption rate of the medicine after nasal spray is low, the medicine effect is limited, and other mild and effective modes for replacing the nasal spray administration mode of children are urgently needed.

In the past, researchers thought that oxytocin could not be taken orally because the degradation of oxytocin in gastrointestinal tract occurred mainly in intestinal fluid, and the physical barrier for peptide transport into blood was mucosa, we did not determine how much peptide substance could enter peripheral blood circulation system after oxytocin was decomposed into macromolecular peptide substance by endopeptidase of gastrointestinal tract, and whether oxytocin decomposed substance in peripheral blood could enter cranium brain through blood brain barrier and combined with oxytocin receptor to play a role. Notably, recent animal molecular studies have demonstrated that oxytocin is transported into the brain by binding to the receptor of the advanced glycation end product, RAGE, in blood brain barrier endothelial cells, and that RAGE not only plays a role in the blood brain barrier but also in the blood-cerebrospinal fluid barrier, RAGE also being present in human brain vascular endothelial cells, thus it is reasonable to believe that its physiological properties are not different in mice and humans.

Furthermore, in recent experiments in which humans have been the subject of research, it has been shown that, compared to nasal oxytocin, the administration of oxytocin in spray form under the tongue of the mouth results in a significant increase in the concentration of oxytocin in the peripheral blood, increasing the level of arousal and associated brain reward responses of an individual to the face, and such brain reward responses are influenced by changes in the concentration of oxytocin in the blood. Thus, we have reason to believe that oxytocin enters the peripheral blood via the oral cavity and intestinal tract not only can pass through the blood brain barrier, but the passing moiety can still bind to oxytocin receptors, regulating social cognitive levels and behavior in human subjects.

Disclosure of Invention

In order to solve the technical problems in the prior art, the present invention aims to provide a way of oral administration of oxytocin, non-peptide agonists thereof and/or antagonist modulators thereof with lollipop as a carrier, to simplify the administration procedure, in particular to improve compliance and success rate of administration to children, further to improve the therapeutic effect on the symptoms of autism in children, and also to oral administration of other peptides, including insulin, for the treatment of diabetes, and Orexin-a (Orexin-a), for the treatment of narcolepsy.

The technical scheme adopted by the invention is as follows:

in a first aspect, the invention provides a method of oral administration using a lollipop carrier, whereby an operator directs a child to lick a lollipop carrier comprising oxytocin, a non-peptide agonist thereof and/or an antagonist modulator thereof.

By adopting the technical scheme, the medicine is combined with the lollipop which children like to lick, so that the children suffering from the autism can take the medicine by licking the lollipop, the conflict psychology of the children suffering from the autism on medicine taking treatment is reduced, the compliance of the children in medicine taking treatment is improved, the oxytocin administration program is simplified, compared with a nasal spray administration mode, the discomfort caused to the children in the administration program is greatly reduced, and the administration success rate is increased.

As a preferred embodiment, the lollipop carrier comprises a lollipop body and a handheld stick, wherein the lollipop body is an elliptic cylinder with a long diameter of 2-4 cm, a short diameter of 2-3 cm and a thickness of 0.5-1.5 cm, a groove with a diameter of 0.5-1.5 cm and a depth of 0.1-0.3 cm is formed in the center of the lollipop body, and a powdery medicament is uniformly attached to the groove. The method is characterized in that oxytocin, a non-peptide agonist and/or an antagonistic regulator medicament of oxytocin is attached to a lollipop carrier, so that children are guided to lick the lollipop, the oxytocin, the non-peptide agonist and/or the antagonistic regulator medicament of oxytocin in a groove are dissolved under the action of saliva while the children lick the lollipop, a small amount of oxytocin enters a nasal cavity through the oral cavity and is absorbed by trigeminal nerve endings, a large amount of oxytocin enters the gastrointestinal part along with the saliva and is decomposed and transported into a peripheral blood circulation system, the oxytocin can be transported into the brain through RAGE at the blood brain barrier part through the peripheral blood circulation, and the oxytocin is combined with corresponding receptors at amygdala and other brain areas to play a role, so that the symptom of autism of the children is improved, and the mood disorder is treated.

As a preferred embodiment, the lollipop body is made of raw materials including: isomalt, citric acid, annatto, blueberry juice, turmeric, sweet orange oil, stevioside, beta-carotene.

Further, the preparation method of the lollipop body comprises the following steps:

step 1: weighing isomaltitol, citric acid, annatto, blueberry juice, turmeric, sweet orange oil, stevioside and beta-carotene;

step 2: mixing isomaltitol, citric acid, annatto, blueberry juice, turmeric, sweet orange oil, stevioside and beta-carotene uniformly, adding water, mixing, dissolving, filtering, decocting with steam, stirring, vacuum sterilizing, maintaining for 4-6h, and concentrating to obtain massecuite meeting the process requirements;

and step 3: and (3) carrying out temperature adjustment sugar kneading on the massecuite obtained in the step (2), and shaping by using a mould to obtain a finished lollipop body.

By adopting the technical scheme, the isomaltitol is adopted as the raw material, and can not be fermented and utilized by bacteria generating dental caries in the oral cavity, so that the growth of streptococcus and the generation of acid are inhibited; secondly, when the xylitol is chewed, the saliva secretion can be promoted, more saliva can wash bacteria in oral cavity and teeth, the concentration of basic amino acid and ammonia at saliva and decayed tooth spots can be increased, the decrease of the pH value in the oral cavity is slowed down, acidic substances which harm the teeth are neutralized and diluted, and the adsorption of the bacteria on the surfaces of the teeth is inhibited, so that the acid erosion of the teeth is reduced, the decayed teeth of children are prevented, the generation of dental plaque is reduced, and the health of the teeth is consolidated; citric acid, annatto and blueberry juice are added, so that the acidity and sweetness of the lollipop can be increased, and children like to eat the lollipop; stevioside has the characteristics of high sweetness and low heat energy; the beta-carrot has the effects of regulating the intestinal function, preventing diarrhea, generating nutrient substances and inhibiting the generation of putrefaction products in a field; the raw material components are reasonably selected and scientifically proportioned, and the components are mutually influenced and interacted, so that the composition plays a synergistic role in improving and treating the symptoms of the infantile autism.

Further, the lollipop body has a pH value ranging from 4 to 6.

Furthermore, the surface of the lollipop body is adhered with the sour agent particles, and the sour agent particles can be absorbed in a mode of saliva secretion of salivary glands of children's oral cavities and dissolution of the lollipop, so that the absorption rate of the medicine is increased.

In another aspect, the present invention provides a process for the preparation of a lollipop comprising oxytocin, a non-peptide agonist thereof and/or an antagonistic modulator thereof, comprising the steps of:

step 1: dissolving oxytocin powder, non-peptide agonist and/or antagonist thereof 10mg in 10ml physiological saline for injection to form solution with the concentration of 600 IU/ml;

step 2: dripping 40ul or 80ul of solution into the groove of the lollipop body one by using a 10-100ul pipette to form a solid medicament containing 24IU or 48IU of oxytocin, a non-peptide agonist thereof and/or an antagonist thereof in each lollipop;

and step 3: putting the prepared lollipop containing oxytocin, non-peptide agonist and/or antagonist thereof on a freeze-drying tray padded with tin foil paper, putting a fruit tray rack placed with the freeze-drying tray in a cold trap of a freeze dryer, and slowly cooling to-56 ℃. After about 4 hours, the fruit tray frame is placed in a glass jar on the upper layer of the freeze dryer, a vacuumizing procedure is carried out for about 18 hours, after the water condensed in the freeze dryer is pumped, an inflation valve is opened slowly, after the air pressure is increased to 101kpa, the lollipop attached with the solid medicament powder is taken out, and the biological activity of the exogenous oxytocin, the non-peptide agonist thereof and/or the antagonist thereof cannot be influenced by the freeze drying mode.

And 4, step 4: packaging all prepared lollipop bodies containing oxytocin, non-peptide agonist and/or antagonist thereof with packaging paper, refrigerating at-80 deg.C, placing in-20 deg.C refrigerator 24 hr before use, and placing in 4 deg.C refrigerator half an hour before use

In summary, due to the adoption of the technical scheme, the invention has the beneficial effects that:

1. according to the invention, by combining the medicine with the lollipop which children like to lick, the children suffering from autism can take medicine by licking the lollipop, so that the conflict psychology of the children suffering from autism on medicine taking treatment is reduced, the compliance of the children in medicine taking is improved, the oxytocin administration program is simplified, compared with the nasal spray administration mode, the discomfort caused to the children in the administration program is greatly reduced, and the administration success rate is increased.

2. Oxytocin, a non-peptide agonist thereof and/or an antagonistic regulator medicament thereof are attached to a groove on a lollipop carrier, when a child licks the lollipop, the oxytocin, the non-peptide agonist thereof and/or the antagonistic regulator medicament thereof in the groove are dissolved under the action of saliva, a small amount of the oxytocin enters a nasal cavity through the oral palate and is absorbed by trigeminal nerve endings, a large amount of the oxytocin enters the gastrointestinal part along with the saliva and is decomposed and transported into a peripheral blood circulation system, the oxytocin can be transported into the brain through peripheral blood circulation at the blood brain barrier by RAGE, and the oxytocin, the non-peptide agonist thereof and/or the antagonistic regulator medicament thereof are combined with corresponding receptors to play a role, so that the symptom of the infantile autism is improved, and the emotional disorder is treated.

3. The isomaltitol is used as a raw material, so that acidic substances which harm teeth in the oral cavity can be neutralized and diluted, and the adsorption of bacteria on the surface of the teeth is inhibited, so that the acid erosion of the teeth is reduced, the decayed teeth of children are prevented, the generation of dental plaque is reduced, and the health of the teeth is consolidated; citric acid, annatto and blueberry juice are added, so that the acidity and sweetness of the lollipop can be increased, and the eating taste of the lollipop is increased; stevioside is added to ensure that the lollipop has sweetness and the heat of the lollipop is reduced; the beta-carrot has the effects of regulating the intestinal function, preventing diarrhea, generating nutrient substances and inhibiting the generation of putrefaction products in a field; the raw material components are reasonably selected and scientifically proportioned, and the components are mutually influenced and interacted, so that the composition plays a synergistic role in improving and treating the symptoms of the infantile autism.

4. The lollipop for improving the symptoms of the infantile autism is formed by combining the components of a special formula, and the practice proves that the lollipop can effectively intervene and treat the autism on the premise of meeting the nutritional requirements of the children with the autism, and does not generate any side effect. When the medicine is taken, the medicine is easy to be accepted and insist by autistic children, the cost is low, and the effect is good. The preparation method of the lollipop is simple and convenient to operate and low in cost. The application of the lollipop for improving the symptoms of the infantile autism provides another possible way for treating the infantile autism, and has important significance.

Drawings

Preferred embodiments of the invention will now be described by way of example only with reference to the accompanying drawings, in which:

FIG. 1 is a schematic structural view of a lollipop carrier according to an embodiment of the present invention;

FIG. 2 is a flow chart of the anti-eye jump paradigm used in study two;

figure 3 is a line graph of the mean change in the concentration of oxytocin in the blood of participants 15min before and 15min every interval after oral administration of oxytocin lollipop, respectively;

FIG. 4 shows a line graph of the mean change in salivary oxytocin concentration in participants 15min before, 30min after and 120min after oral administration of oxytocin lollipop, respectively;

figure 5 is a bar graph of the percent of false responses to social stimuli in the oxytocin group on the reversal task compared to the placebo group after completing the reversal eye jump paradigm by nasal, sublingual, and oral oxytocin lollipops.

Reference numerals

1-lollipop body, 2-handheld stick, 3-groove, 4-medicament and 5-sour agent particle.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all the embodiments. The components of embodiments of the present application, generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations. Thus, the following detailed description of the embodiments of the present application, presented in the accompanying drawings, is not intended to limit the scope of the claimed application, but is merely representative of selected embodiments of the application. All other embodiments, which can be derived by a person skilled in the art from the embodiments of the present application without making any creative effort, shall fall within the protection scope of the present application.

In the description of the embodiments of the present application, it should be noted that the terms "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings or orientations or positional relationships that the products of the present invention are usually placed in when used, and are only used for convenience of description and simplicity of description, but do not indicate or imply that the devices or elements that are referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present application. Furthermore, the terms "first," "second," "third," and the like are used solely to distinguish one from another and are not to be construed as indicating or implying relative importance.

The present invention will be described in detail with reference to fig. 1 to 5.

Example 1:

the invention provides a lollipop carrier, referring to fig. 1, the lollipop carrier comprises a lollipop body 1 and a handheld stick 2, the lollipop body is an elliptical cylinder with a long diameter of 3cm, a short diameter of 2.5cm and a thickness of 1cm, a groove 3 with a diameter of 1cm and a depth of 0.1-0.3 cm, preferably 0.2-0.3cm is arranged in the center of the lollipop body 1, and oxytocin, a non-peptide agonist thereof and/or an antagonistic regulator thereof and other peptide powdery medicaments 4 are uniformly attached to the groove 3.

In this embodiment, the lollipop body 1 is flat. When eating the flat lollipop, the oxytocin agent 4 on the surface is more easily absorbed than when eating a round lollipop.

In this embodiment, the surface of the lollipop body 1 is attached with particles 5 of sour agent. By adopting the preferable technical scheme, the sour agent particles 5 can be absorbed in a mode of saliva secretion of salivary glands of the mouth of the child and lollipop dissolution, so that the absorption rate of the medicine is increased.

In this embodiment, the lollipop body 1 is made of the following raw materials: isomalt, citric acid, annatto, blueberry juice, turmeric, sweet orange oil, stevioside, beta-carotene.

Example 2:

the invention also provides a preparation method of the lollipop body 1, which comprises the following steps:

step 2: mixing isomaltitol, citric acid, annatto, blueberry juice, Curcuma rhizome, sweet orange oil, stevioside and beta-carotene uniformly, adding water, mixing, dissolving, filtering, decocting with steam, stirring, vacuum sterilizing for 4-6h, and concentrating to obtain massecuite meeting the process requirements;

and step 3: and (3) carrying out temperature adjustment sugar kneading on the massecuite obtained in the step (2), and shaping by using a mould to obtain a finished lollipop body 1.

In this embodiment, the lollipop body 1 has a pH in the range of 4 to 6.

Example 3:

in another aspect, the present invention provides a method for preparing a lollipop comprising oxytocin, a non-peptide agonist thereof and/or an antagonistic modulator thereof, comprising the steps of:

step 2: dripping 40ul or 80ul of solution into the groove 3 of the lollipop body 1 one by using a 10-100ul pipette to form a solid medicament 4 containing 24IU or 48IU of oxytocin, a non-peptide agonist thereof and/or an antagonist thereof in each lollipop;

and step 3: putting the prepared lollipop containing oxytocin, non-peptide agonist and/or antagonist thereof on a freeze-drying tray padded with tin foil paper, putting a fruit tray rack placed with the freeze-drying tray in a cold trap of a freeze dryer, and slowly cooling to-56 ℃. After about 4 hours, the fruit tray is placed in a glass jar on the upper layer of the freeze dryer, a vacuumizing procedure is performed for about 18 hours, after the water condensed in the freeze dryer is pumped, the inflation valve is opened slowly, and after the air pressure is increased to 101kpa, the lollipop with the solid medicament 4 powder is taken out.

And 4, step 4: all prepared lollipop bodies 11 containing oxytocin, non-peptide agonists and/or antagonists thereof are packaged with wrapping paper, then refrigerated in a refrigerator at-80 ℃, put into a refrigerator at-20 ℃ 24 hours in advance when used, and finally put into a refrigerator at 4 ℃ half an hour before use.

Example 4:

in another aspect, the invention provides a method for oral administration of a lollipop carrier, wherein an operator directs a child to lick a lollipop carrier comprising oxytocin, a non-peptide agonist thereof and/or an antagonist modulator thereof in accordance with a fixed program.

To further demonstrate the beneficial effects achieved by the present invention, the following experimental data are also provided:

the first study is as follows: a randomized, single-blind, pre-and post-control study was performed in which 10 healthy adult males were randomly selected and randomly assigned to complete an oral oxytocin-containing lollipop trial. All participants were informed of both Oxytocin (OT) and placebo lollipops, wherein the placebo ingredient was a solution of glycerol and normal saline, which did not differ in taste and powder morphology after crystallization. Blood and saliva are collected once before the lollipop is taken orally, the lollipop is taken orally for 3min immediately, the second blood is collected after the lollipop is stood still for 12min, and then the blood is collected once every 15min, 5ml each time, 10 times and 50ml in total. The second and third saliva collection are carried out after 40 minutes (fourth blood collection) and 120min (tenth blood collection) of oral lollipop, and each saliva is not less than 1 ml.

This study was mainly to investigate the effect of oral oxytocin lollipop on the change in the concentration of oxytocin in the peripheral blood and how long this effect can last.

The participants were healthy men between 18-30 years of age, had no history of mental illness, alcohol abuse, and clinically relevant physical illness, and had not taken any medications one month prior to the experiment. The entire experiment was completed by 10 participants (M21.24 years old, SD 2.59). Oxytocin used in the experiment was supplied by Sichuan American pharmaceutical Co.

As shown in fig. 3 and fig. 4, significant increases in OT blood concentration were observed at the time points 15, 30 and 45min after oral administration of oxytocin lollipop (p ═ 0040, p ═ 0066 and p ═ 043), indicating that most of oxytocin enters the peripheral blood system through RAGE transport after entering the gastrointestinal tract via the oral cavity, resulting in significant increases in OT concentration in the peripheral blood. Further to investigate whether this increased peripheral blood OT concentration could also enter the blood brain barrier and affect social cognition in individuals, we conducted a second study.

Study two: to investigate whether the effect of oxytocin lollipop vectors on individuals in social cognitive tasks was consistent with previous findings, researchers used eye-tracking technology (EyeLink 1000Plus system, SR Research, Ottawa, Canada) to recruit 220 college students to perform a randomized, double-blind, placebo-controlled study, exploring evidence of peripheral oxytocin entry into the brain to modulate social responses by three modes of administration, nasal spray, tongue spray and lollipop.

The participators are healthy men between 18-30 years old, right handedness, Han nationality, heterosexual love and non-smokers, have no any nervous system and mental disease diseases, have no drug use in the month before the experiment, and stop taking drinks and foods containing alcohol and caffeine in 24 hours before the experiment. All participants are randomly distributed to a placebo group or an oxytocin group with three administration modes, files are filled before administration, practice experiments are started after 30min of rest after administration, and formal experiments are completed after the participants understand the experiment flow.

Participants first completed the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI-II), Social response Inventory (SRS), adult Autism Spectrum Inventory (ASQ), Positive and Negative emotion Inventory (PAIR), orally administered a lollipop containing oxytocin or placebo after first collecting saliva, blood, followed by a second NAS stick, saliva collection, 5ml of blood, 1ml of saliva each, followed by completion of an adapted counter-eye jump paradigm, followed by a PANAS post-task, to be asked to guess whether they may have taken a lollipop containing oxytocin or no-oxytocin. Finally, data for a total of 14 participants were not included in the analysis for experimental or technical reasons.

Fig. 2 shows the flow of the anti-eye-jump paradigm used in study two, with 7 each of the orientation and reverse chunks, occurring randomly, with participants completing the visual tasks under the corresponding chunks according to cue cues. The participants need to watch the white plus fixation point at the center of the screen when each trial time begins, move the sight line from the fixation point to the position where the face picture appears in the chunk, and move the sight line from the fixation point to the blank area where the picture appears in the opposite position in the reverse task, so that the task is required to be fast and accurate.

The anti-eye jump task in this study included five social emotional faces (anger, sadness, happiness, fear, and neutrality), completed by 8 actors (4 men and 4 women), and 8 non-social oval house pictures with slight variations. Each experiment started with 2 non-social chunks (one reverse saccade chunk and one heading saccade chunk), each chunk comprising 48 trials followed by 12 mood chunks (reverse saccade chunk and 6 heading saccade chunk), each chunk comprising 40 trials, 8 trials per mood. The orientation and reverse chunks occur randomly, and the trial times in each chunk also occur randomly. Each chunk starts with a 2000 ms cue, and the participant performs the corresponding heading or reversing task in the next chunk according to the cue "heading" or "reversing" requirements. After the cue word disappears, a '+' fixation point appears, the average duration is 1500ms (time range: 1000-3500ms), and the '+' word is required to be tentatively fixed until the '+' word disappears. Next, the stimulation material appears 1000 milliseconds on the left or right side of the screen. The subject is asked to look at the contralateral area of the stimulus during the "reversal" phase (anti-eye jump state) and to fixate the stimulus itself during the "heading" phase (heading eye jump state). The task had 14 chunks, 576 trials.

As shown in table 1, all questionnaire scores showed no difference between groups after t-test on the questionnaire results, indicating that the study well controlled the effects of anxiety, depression, autism tendency, and mood state before and after drug administration on the experimental results, and better controlled the effects of individual differences.

TABLE 1

As shown in figure 5, three modes of oxytocin application showed a consistent trend in the reverse eye jump task on social stimulation, with a significant increase in the percentage of false responses to social stimulation by the oxytocin group compared to the placebo group (nasal spray: p <. 01; on tongue: p <. 01; lollipop: p <.05), indicating that oral oxytocin lollipop and the other two modes of application both act to modulate the social cognitive activity of the individual.

In conclusion, the combination of the two research results shows that the lollipop containing oxytocin can pass through the blood brain barrier after being absorbed by intestines and stomach and entering peripheral blood, and is combined with an oxytocin receptor in the intracranial to influence social cognition and a certain process of emotional processing of participants. From the foregoing, it will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein, and any reference signs in the claims are not intended to be construed as limiting the claim concerned.

It should be noted that the lollipop body prepared by the raw materials and the method provided by the invention achieves the same or similar effect as the lollipop disclosed in the prior art, and is used for improving the taste of the lollipop and increasing the effect of adjuvant therapy.

The regimen is not limited to adjuvant treatment of autism in children, but is applicable to both insulin for diabetes treatment and Desmopressin (Desmopressin) for temporary diabetes insipidus treatment.

Claims

1. A method of oral administration of a lollipop carrier, wherein an operator directs a child to lick a lollipop carrier containing oxytocin, a non-peptide agonist thereof and/or an antagonist modulator thereof.

2. The method for oral administration using lollipop as carrier according to claim 1, wherein the lollipop carrier comprises a lollipop body (1) and a hand-held stick (2), the lollipop body is an elliptic cylinder having a long diameter of 2 to 4cm, a short diameter of 2 to 3cm and a thickness of 0.5 to 1.5cm, the lollipop body (1) has a groove (3) having a diameter of 0.5 to 1.5cm and a depth of 0.1 to 0.3cm at the center, and the powdered medicament (4) is uniformly adhered to the groove (3).

3. The method for oral administration with lollipop as carrier according to claim 2, wherein the lollipop body (1) is made of raw materials comprising: isomalt, citric acid, annatto, blueberry juice, turmeric, sweet orange oil, steviol glycosides and beta-carotene.

4. A method for oral administration with a lollipop as carrier according to claim 3, characterized in that the lollipop body (1) is made by the following method:

and step 3: and (3) carrying out temperature-adjusting sugar kneading on the massecuite obtained in the step (2), and shaping by using a mould to obtain a finished lollipop body (1).

5. A method for oral administration with a lollipop as carrier according to claim 3, characterized in that the lollipop body (1) has a pH in the range of 4-6.

6. The method for oral administration with lollipop as carrier in claim 1, wherein the lollipop body (1) is provided with sour agent particles (5) attached to the surface.

7. The method for oral administration with lollipop as carrier according to any of claims 1 to 6, wherein the method for preparing the drug-containing carrier comprises the steps of:

step 2: dripping 40ul or 80ul of solution into the groove (3) of the lollipop body (1) one by using a 10-100ul range pipette to form a solid medicament containing 24IU or 48IU of oxytocin, a non-peptide agonist thereof and/or an antagonist thereof in each lollipop;

and step 3: putting the prepared lollipop containing oxytocin, a non-peptide agonist and/or an antagonist thereof on a freeze-drying tray filled with tinfoil paper, putting a fruit tray rack with the freeze-drying tray in a cold trap of a freeze-drying machine, slowly reducing the temperature to-56 ℃, putting the fruit tray rack in a glass tank on the upper layer of the freeze-drying machine after about 4 hours, performing a vacuum-pumping program for about 18 hours, slowly opening an inflation valve after water condensed in the freeze-drying machine is pumped, and taking out the lollipop with the powdery medicament (4) attached to the interior of the groove (3) after the air pressure is increased to 101 kpa;

and 4, step 4: all prepared lollipop bodies (1) containing oxytocin, non-peptide agonists and/or antagonists thereof are refrigerated in a refrigerator at minus 80 ℃ after being packaged by packaging paper, are placed in the refrigerator at minus 20 ℃ 24 hours in advance when being used, and are finally placed in the refrigerator at 4 ℃ half an hour before being used.